Open Collections

UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Photochemistry of medium and large membered ring diketones in both the solution and crystalline state Lewis, Thillairaj Johnathan 1993

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
831-ubc_1993_spring_phd_lewis_thillairaj.pdf [ 9.87MB ]
Metadata
JSON: 831-1.0061803.json
JSON-LD: 831-1.0061803-ld.json
RDF/XML (Pretty): 831-1.0061803-rdf.xml
RDF/JSON: 831-1.0061803-rdf.json
Turtle: 831-1.0061803-turtle.txt
N-Triples: 831-1.0061803-rdf-ntriples.txt
Original Record: 831-1.0061803-source.json
Full Text
831-1.0061803-fulltext.txt
Citation
831-1.0061803.ris

Full Text

PHOTOCHEMISTRY OF MEDIUM AND LARGE MEMBERED RINGDEKETONES IN BOTH THE SOLUTION AND CRYSTALLINE STATEbyTHILLAIRAJ JOHNATHAN LEWISB.Sc., University of Jaffna, Sri Lanka, 1985A THESIS SUBMITTED IN PARTIAL FULFILMENT OFTHE REQUIREMENTS FOR THE DEGREE OFDOCTOR OF PHILOSOPHYinTHE FACULTY OF GRADUATE STUDIES(DEPARTMENT OF CHEMISTRY)we accept this thesis as conformingto the required standardTHE UNIVERSITY OF BRITISH COLUMBIAMarch 1993© Thillairaj Johnathan Lewis, 1993In presenting this thesis in partial fulfilment of the requirements for an advanceddegree at the University of British Columbia, I agree that the Library shall make itfreely available for reference and study. I further agree that permission for extensivecopying of this thesis for scholarly purposes may be granted by the head of mydepartment or by his or her representatives. It is understood that copying orpublication of this thesis for financial gain shall not be allowed without my writtenpermission.(Signature)Department of ^H ASTY yThe University of British ColumbiaVancouver, CanadaDate  0%141 AP i2.1 L 1(193 DE-6 (2/88)ABSTRACTThe type II photochemistry of nine diametric cyclic diketones (ten, twelve,fourteen, sixteen, eighteen, twenty, twenty-two, twenty-four and twenty-six memberedrings), two non-diametric cyclic diketones (sixteen and seventeen membered rings) andtwo cyclic keto-alcohols (sixteen and eighteen membered rings) was studied in both solidand solution media in order to investigate the relationship between conformation andphotoreactivity. Upon irradiation, most compounds investigated underwent smoothy-hydrogen abstraction. The stereoelectronic requirements for the y-hydrogen atomabstraction and the reactivity differences observed in the solid and solution reactions havebeen investigated with the help of X-ray crystallography and molecular mechanicscalculations.Stereoselective cyclization was observed during the solid state photoreactions ofall diketones investigated, with the exception of the ten, fourteen and seventeen memberedring compounds. The stereochemistry of the major solid state product correlated wellwith the hydrogen abstraction geometry found in the solid state conformation. Uponirradiation in solution, in rings larger than fourteen membered, the stereoselectivity islargely lost, but a slight preference for trans over cis cyclobutanol formation together withfairly large amounts of cleavage product formation were observed. In smaller rings,however, the product distributions in solution were quite similar to those observed in thesolid state.In the above series of diketones, two groups of y-hydrogen atoms can bedistinguished with respect to their stereoelectronic dispositions in the solid stateconformations. The y-hydrogens having close 0.-H contacts (<2.78 A) with the carbonyloxygen atoms make a boat-like abstraction geometry, whereas the other type ofy-hydrogens with longer 0.-H contact distances (close to 3 A) make a chair-likeabstraction geometry. The geometric parameters for abstraction of all closest y-hydrogenatoms on each diketone remain close to their average values of d = 2.72 A, 01) = 52.4°,A = 82.4°, 0 = 114.7°.In non-diametric diketones the chemically non-equivalent 7-hydrogen atoms leadto the possibility of forming regioisomeric pairs of cyclization and cleavage products. Inthe solid state conformation of the sixteen membered non-diametric diketone, the non-equivalent 7-hydrogen atoms differ further in their stereoelectronic dispositions. Theregioselectivity observed in this diketone reveals an efficient abstraction of the y-hydrogenatoms having close 0...H contacts (boat-like abstraction geometry), and almost noabstraction for the 7-hydrogen atoms with 0...H contacts close to 3 A (chair-likeabstraction geometry).Interestingly, four diketones exhibit solid-solid phase transitions at elevatedtemperatures. In an attempt to investigate such solid state behavior, photochemicalreactions were performed at various temperatures above and below the transitiontemperature, together with solid state NMR (13C CPMAS, deuterium wide line NMRtechniques), solid state FTIR and X-ray powder diffraction studies. The phase transitionsof three of the four diketones are reversible in nature, and above the transition points themolecular behaviour with regard to the photochemistry resembles that in isotropic fluidmedia.The X-ray crystal structure analysis of the two crystal modifications of the twentysix membered ring diketone, cyclohexacosane-1,14-dione, reveals the existence of"conformational polymorphism". The solid state photochemistry of these dimorphs showsa divergent photochemical behaviour, and such differences have been shown (with the helpof the X-ray crystal structures), to be the result of conformational factors rather thanpacking effects. Investigations also reveal an irreversible solid-solid phase transformationof one of these two crystal modifications into its dimorph.ivIn diketones, substitution of at least one of the a-hydrogen atoms with a methylgroup (one methyl group at each a-carbon atom) completely changes the photoreactionpathway to yield type I products exclusively.Photolysis of three diametric diketones (sixteen, eighteen and twenty memberedrings) included in zeolites afforded both Norrish type I and type II photoproducts.TABLE OF CONTENTSpagesABSTRACT^LIST OF FIGURES ^ixLIST OF TABLES ^xviACKNOWLEDGEMENTS ^xviiiINTRODUCTIONCHAPTER I1.0. General ^11.1. The Topochemical principle ^21.1.1. Bimolecular reactions ^31.1.2. Non-topochemical photodimerization ^61.2. The concept of the reaction cavity ^101.3. Unimolecular reactions ^141.4 Type II reaction ^171.4.1. Geometrical relationship for hydrogen abstraction ^191.5. The Norrish type I reaction ^221.6. Polymorphism and solid-solid phase transitions in crystals ^241.7. Conformational analysis of medium sized ring and macrocycliccompounds ^261.8. Objectives of current research ^32RESULTS AND DISCUSSIONCHAPTER II2.0. Preparation of starting materials ^36vipagesCHAPTER III3.0. Photochemistry of medium and macrocyclic diketones that undergotype II reactions ^463.1. Photochemistry of diametric diketones ^493.1.1. Structural determination of the photoproducts ^513.1.2. Photochemistry of non-diametric diketones ^543.1.3. Photochemistry of cyclic keto-alcohols ^573.2. Diketones that give cis-cyclobutanol derivative as the majorphotoproduct in the solid state ^623.2.1. Solid state conformation and photochemistry ^623.2.2. Hydrogen abstraction geometry and biradical geometry ^653.2.3 Structure reactivity correlation ^683.2.4 Singlet and triplet reactions.of diketones ^703.3. Diketones that give trans-cyclobutanol as the major product in thesolid state ^843.3.1. Solid state conformation and photochemistry ^843.3.2. Hydrogen abstraction geometry and biradical geometry ^863.3.3. Structure reactivity correlation ^883.4. Diketones in which the stereoselectivity is significantly lowered inthe solid state ^913.5. Chemoselectivity in the solution and solid state photoreactions ofdiketones ^993.6. Photochemistry of the ten membered ring diketone ^1053.7. The best geometrical requirements for 7-hydrogen abstractionin diketones ^109viipagesCHAPTER IV4.0. Polymorphism, solid-solid phase transitions and solid phase orderdependent photochemistry of diketones ^113CHAPTER V5.0. The photochemistry of alkylated cyclic diketones ^1485.1. The photochemistry of cyclic mono- and diketones in zeolites ^156EXPERIMENTAL.CHAPTER VI6.0. General information ^1656.1. Synthesis of starting materials ^1696.1.1. Synthesis of diametric diketones by ozonolysis of bicyclicolefins ^1696.1.2. Synthesis of diametric diketones by Blomquist's high dilutiontechnique ^1716.1.3. Synthesis of non-diametric diketones by Blomquist's highdilution technique ^1796.1.4. A miscellaneous reaction from pimeloyl chloride under highdilution technique ^1816.1.5. Synthesis of diametric diketone by Dieckmann condensationreaction ^1826.1.6. Synthesis of cyclic keto-alcohols by partial reduction ofdiketones ^1846.1.7. Synthesis of tetramethylated diketones ^1876.1.8. Deuteraction of diketones ^189viiipages6.2. Photochemical studies ^1916.2.1. General ^1916.2.2. Photochemistry of diametric diketones ^1946.2.3. Photochemistry of non-diametric diketones ^2136.2.4. Photochemistry of keto-alcohols ^2206.2.5. Photochemistry of tetramethylated diketones ^2206.3. Quantum yield studies ^2236.4. Quenching studies ^2266.5. Computational generation of diketone geometries ^227BIBLIOGRAPHY ^230ixLIST OF FIGURESFigures^ Caption^ pages1. Compounds displaying medium dependent photoreactivity ^32. Solid state photochemistry of the three crystal modifications oftrans-cinnamic acid ^43. A few examples of solid state photodimerization ^74. Three crystal modifications of anthracene derivatives ^95. (1) Favorable and (2) unfavorable solid state reactions in thereaction cavity ^116. Photochemistry of a diacyl peroxide ^127. Steric compression control of compound 4 ^138. The cobaloxime complex ^149. Photochemistry of (a) ene-diones, (b) cyclohexenones, (c) 13, 'y-unsaturated ketones, (d) arylketones and (e) 1,4-dienes ^1710. Type II reaction ^1811. Geometrical parameters for the abstraction of hydrogen atom bythe carbonyl oxygen atom ^2012. Theoretically ideal values of the geometrical parameters forhydrogen abstraction by the carbonyl oxygen ^2213.^The a-cleavage processes (Norrish type I reaction) of cyclicketones ^23pages14. Types of phase transitions^ 2515. The^solid^state^conformation^of^cis-1,6-diaminocyclodecanedihydrochloride 2716. The diamond lattice conformation of the ten membered carbonframe^ 2717. The solid state conformation of cyclododecane^ 2818. Strain-free diamond lattice carbon frame of the fourteen memberedring^ 2919. The corner positions of cyclic compounds^ 3020. Transformation of the cyclohexadecane molecular conformationfrom square [4444] (diamond lattice) to rectangular [3535]^ 3121. Diametric diketones^ 3222. (a) Cisoid,^(b) gauche (pre-cis),^(c) gauche @re-trans) and (d)transoid or anti conformational arrangements of the biradicalintermediates 3423. Synthesis of the ten and twelve membered ring diketones viaozonolysis of bicyclic olefins^ 3624. Synthesis of diketones from diacyl derivatives^ 3725. A possible mechanism for the formation of diketones^ 3926. A possible mechanism for the formation of y-pyrone^ 4127. Fate of adipoyl chloride under different synthetic conditions ^ 42xipages28. Synthesis of non-diametric diketones ^4429. Methylation of diketones ^4530. Photolysis of monoketones in cyclohexane ^4631. A UV-VIS spectrum of 10-2 M diketone 9 in cyclohexane ^4832. Photolysis of diametric diketones in cyclohexane ^5033. Newman projection of cis and trans-cyclobutanol derivatives downthe ring junction ^5334. 1H ntrir spectrum of allyl moiety of ene-dione 13e ^5535. Photolysis of non-diametric cyclic diketones ^5636. Photolysis of cyclic keto-alcohols ^5837. Solid state conformations of (a) twelve membered (MM2),(b) sixteen membered, (c) sixteen membered (non-diametric),(d) twenty membered, (e) twenty-four membered and (f) twenty-sixmembered ring diketones ^6438. Newman projections of boat-like and chair-like abstractiongeometries down the C2-C3 carbon-carbon bonds ^6539. (a) Pre-cis biradical intermediate of diketone 9. (b) Biradicalintermediate reaction center ^6840.^(a) Ene-dione / trans-cyclobutanol versus quencher concentrationplot. (b) Ene-dione / cis-cyclobutanol versus quencherconcentration plot ^72xiipages41. Singlet and triplet pathways of type II reactions in diketones^7342. Diagrammatic representation of the formation of cis-cyclobutanolderivative 9c by the concerted cyclization of the solid stateconformation of diketone 9 ^7443. Possible low energy conformations of diketone 9 generated byMM2 ^7844. Possible low energy conformations of diketone 7 generated byMM2 ^8445. Solid state conformations of (a) eighteen, (b) twenty two,(c) twenty six (needles) membered ring diketones ^8646. Newman projection of the boat-like and chair-like abstractiongeometries down the C2-C3 carbon-carbon bonds ^8847. (a) Biradical intermediate from diketone 10, (b) Biradicalintermediate reaction center ^9048. Solid state conformation of the fourteen membered ring diketone 8.^9149. Five low energy conformations of diketone 8 generated by MM2....^9650. Conformational change from 8A to 8B ^9751. A diagrammatic representation of the biradical intermediatereaction center showing 01, 02 and 0 dihedral angles ^10052. Conformational interchange (pseudorotation) of cyclododecanonebiradical intermediate from gauche to anti conformation ^10553.^The X-ray crystal structure of diketone 6 ^106pages54. y and 6-Hydrogen abstraction pathways of cyclodecanone ^10755. Three possible low energy conformations of diketone 6 generatedby MM2 ^10856. The ORTEP stereodiagram of unit cell packing of (a) Plate (viewedfrom "a" axis), and (b) Needle (viewed from "b" axis) crystals ofdiketone 14 ^11557. Solid state photochemistry of a-adamantyl-p-chloroacetophenone..^11658. Differential scanning calorimetry thermograms of (a) Plate and (b)Needle crystal modifications of 14 ^11859. The powder diffraction patterns obtained for the (a) Plate, (b)Needle and (c) Annealed plate forms of 14 at roomtemperature ^11960. The solid state FTIR spectra of (a) Plates at 20°C, (b) Plates at60°C and (c) Needles at 20°C in KBr matrices. (d) A solutionspectrum of diketone 14 recorded in CC14 ^12261. trans-1-(4-Pentanoylpheny1)-4-pentylcyclohexane (46) and trans-1-hepty1-4-(4-pentanoylphenyl) cyclohexane (47) ^12562. 13C CP/MAS Spectra of Plates (a) at 27°C and (b) at 57°C, (c) 13CNMR spectrum of diketone 14 in hexane ^12963. The aliphatic region of diketone 14 in 13C CP/MAS spectra from(a) Plates at 27°C, (b) Plates at 57°C, (c) Annealed plates at 27°Cand (d) Needles at 27°C ^13064.^Differential scanning caloiimetry thermograms of (a) Diketone 9,(b) Diketone 10, and (c) Diketone 15 ^132xivpages65. The solid state FTIR spectra of diketone 9 recorded at (a) 20°C, (b)35°C, (c) 40°C in KBr matrices. (d) A solution spectrum ofdiketone 9 recorded in CC14 ^13566. 13C CP/MAS spectra of diketone 9 at (a) 27°C, (b) 37°C, and (c) asolution 13C NMR recorded in CDC13 ^14167. The expanded methylene region of diketone 9 at 27°C(13CP/MAS) ^14168. 2H NMR spectrum of diketone 9 (a) at 27°C and at37°C ^14269. 13C CP/MAS spectrum of the carbonyl region of diketone 9 at32°C ^14470. 13C CP/MAS spectra of diketone 10 (a) at 27°C and (b) 92°C. (c)A solution 13C NMR spectrum of diketone 10 recorded inCDC13 ^14671. 21-1 NMR spectra of diketone 10 (a) at 27°C and (b) 82°C ^14772. Photoepimerization of tetramethylated diketones in the solidstate ^14873. The ORTEP stereodiagrams of the sixteen membered ring diketone2R*,8S*,10R*,16S*-tetramethylcyclohexadecane-1,9-dione^(31)and^the^twenty-four^membered^ring^diketone2R*, 12S *,14R*,24S *4etramethylcyclotetracosane-1,13-di one (32)^15174. Type I and type II products from the photolysis of 2-methylcyclododecanone ^15375.^Photolysis of iii- and tetramethylcyclodecanone ^153XVpages76. Photolysis of 2,n-diphenylcycloalkanones.  ^15477. A diagrammatic representation of possible diastereomers oftetramethylated sixteen membered diketone (31), at thephotostationary state ^15578. The two modes of photoreaction of mono and diketones inzeolites ^15779. Enhancement of type I products in zeolite NaY with respect to thesolution reaction ^15880. Dependence of type I to type II product ratio on the cation ^15881. Illustration of the [SiO414- and [A104]5- tetrahedra that are theprimary building blocks of zeolites. Also shown are representationsof the sodalite cage, zeolites (A, X and Y) and the unit cellcompositions of X and Y zeolites  16082. Cation locations inside the faujasite cages ^16183. Electronic interaction of lithium cation with the carbonylchromophore impedes type II hydrogen abstraction sterically^16384. Diagram illustrating the partitioning of the type 11 (65) and type I(68) biradical intermediates to products and to their startingketones ^16385. Apparatus used for the analytical photoreactions at elevatedtemperatures ^19286. The flow diagram showing the "Monte Carlo Multiple-Minimum"conformational search ^228xviLIST OF TABLESTables^ Caption^ pagesI.^Percentage yields of diketones and 7-pyrones ^38Product percentages from the irradiation of monoketones incyclohexane ^47Methine carbon chemical shifts of the cyclobutanol derivatives ^52IV. Product percentages at zero percent conversion obtained at 20°C^ 61V. The geometrical parameters of the 7-hydrogen atoms ^67VI. Type II product ratios of diketone 9, from direct photolysis andphotolysis with the quencher ^72VII. Quantum efficiencies of type II photoproduct formation fromdiketones 9, 10 and 12 ^80VIII. The 7-hydrogen geometrical parameters of diketones that givetrans-cyclobutanol derivatives as the major solid statephotoproducts ^87IX. Cyclization / cleavage ratios of diketones both in solution and solidstate ^100X. Biradical parameters of diketones ^101XI. Geometrical parameters corresponding to 7-hydrogens having theclosest 0...H contacts ^110xviipagesXII. The geometrical parameters of the biradical intermediatescorresponding to the y-hydrogen atoms having closest 0...Hcontact distances ^112XIII. FTIR band frequencies (cm-1) of annealed plates, needle crystalsand low and high temperature solid phases of plate crystals as afunction of temperature ^123XIV. Product percentage percentages of diketone 14 from (a) Plates, (b)Needles, (c) Annealed plates and (d) isotropic media (hexane) as afunction of temperature ^126XV. Photochemical results of 13-form cinnamic acid as a function oftemperature ^128XVI. Product percentages of diketones (a) 9, (b) 10, and (c) 15 as afunction of temperature and medium ^136XVII. Solvent systems and their corresponding boiling points used foranalytical irradiations at elevated temperatures ^192XVIII.^Internal standards ^225xviiiACKNOWLEDGEMENTI am very grateful to Professor John. R. Scheffer for the valuable guidance andencouragement he gave me throughout the period of my study. His understanding andpatience helped bring this thesis to a successful conclusion.My special thanks go to Professor James Trotter and Dr. Steve Rettig for theX-ray crystallographic analysis. I also wish to express my sincere appreciation toProfessor Trotter for letting me use the computer to print out the MM2 structures.My appreciation is also extended to Professor Larry Weiler, who allowed me touse the Silicon Graphics work station for MM2 calculations. The generous help withthese calculations I received from Leonard Lerner is also gratefully acknowledged.I sincerely thank Professor Colin A. Fyfe and Dr. Leslie H. Randell, whoperformed the solid state NMR studies reported in this thesis, and I would also like tothank Mark Eade, Tony Fu, Ed Graziani and Mylvaganam Murugesupillai forproofreading my thesis.Finally, I would like to acknowledge the dedicated and friendly help of the NMRand Mass spectrometry laboratory staff and the service of the micro-analyst, Mr. P. Borda.CHAPTER I.1.0. General.Chemical reactions induced by sunlight have been a primary factor in the evolutionof life on our planet.1 It is believed that within the first billion years of evolution, plant lifebegan to produce oxygen into the atmosphere. Photolysis of oxygen in the stratospheregenerated ozone, which provided a protective layer by filtering high energy radiation fromsunlight, and was an essential factor in the survival of animal life forms, includingman.2,3,4,5 Despite the fact that chemical changes caused by light have played such asignificant role in the evolution of life, only during the last two centuries have light-induced chemical reactions, so called "photochemical reactions", been systematicallyinvestigated in the laboratory.In recent years, photochemistry has made immense contributions to the field ofchemistry. Large numbers of complex molecules that are essentially unavailable byalternative synthetic methods or which could only be made via tedious synthesisprocedures, can now be elegantly synthesized by photochemistry.Due to a long-standing notion among chemists that chemical reactions requiremobility, molecules in crystals which have very small translational and vibrational motionswere considered unsuitable for chemical reactions. Any studies of chemical reactions weretherefore mainly focused on liquid and gaseous states, which were thought to possess thenecessary molecular freedom. However, the molecular and atomic motions in the solidstate are not as restricted as originally thought.6The history of solid state chemistry can be traced back to the beginning of thenineteenth century. The thermal transformation of crystalline ammonium cyanate to ureaby Friedrich Wohler (1828) could be considered as the first example of a solid statereaction.7 A few years later, in 1834, H. Trommsdorff discovered the first organic solid2state photoreaction, in which crystals of santonin, when exposed to sunlight, turned yellowand cleaved.8 During the course of the late 19th and early 20th centuries, work on solidstate photochemistry increased dramatically, and a wide variety of photochemicalreactions were investigated by the pioneers of photochemistry.9,10,1 1,12,13 These studiescame to a halt mainly due to a lack of understanding of the nature and the structure ofcrystals.During the last forty years spectacular progress has been made in the field of solidstate chemistry. Development of direct methods of crystal structure determination, andthe advent of relatively inexpensive fully automated X-ray diffractometers with digitalcomputers, enable one to obtain pictorial details of the molecular structure and the crystallattice. A crystal structure obtained immediately prior to reaction led to the possibility ofinvestigating structure-reactivity correlations with a deeper understanding of the molecularpacking and the topochemistry in the crystal lattice.Unlike isotropic fluid phases, the molecules in crystals are arranged in aconstraining environment; therefore the photochemical reaction pathways in the solid statetend to be controlled by the crystal lattice. In the majority of cases, the intrinsic reactivityof the molecule is modified in the solid state to yield the lattice-controlled photoproductwith high selectivity. Some examples of such lattice-controlled reactions, which differfrom the intrinsic solution reactivity, are depicted in Figure 1.1.1. The Topochemical Principle.Kohlschutter17 (1918) first proposed this principle, which is the basis of the entirefield of organic solid state chemistry. He stated that the nature and the properties of thesolid state reaction products are governed by the constraining influence of the threedimensional periodic environment present in the crystals, and thus the reactions tend tooccur with a minimum of atomic and molecular motion.(Ref. 14)hvsolutiondimers0(Ref. 15)hvsolution 0hvcrystal(Ref. 16)hvsolution3OHFigure 1: Compounds displaying medium dependent photoreactivity.1.1.1. Bimolecular Reactions:In the early 1960s, after the advent of modern X-ray crystallography, Schmidt andco-workers systematically studied the factors that govern reactions in the organic solidstate, especially the photo-induced [2+2] dimerization reactions of the trans-cinnamic acidsystem,18,19 and confirmed the postulate proposed by Kohlschutter. Thephotodimerization of cinnamic acids in crystals was first observed in 1889 byLiebermann20, and this incomplete work was later reinvestigated by Bernstein andQuimby2i in 1943, who interpreted the formation of a-truxillic and P-truxinic acids fromtwo types of cinnamic acid crystal modifications as lattice-controlled reactions.Schmidt and co-workers, as a result of their extensive studies on these systems,demonstrated a correlation between the crystal structure and the nature of the productsobtained and also a correlation between the crystal structure and the photoreactivity orphotostability of organic substances. These observations support the statement proposedby Kohlshutter, namely that reactions in the solid state proceed with minimum atomic andp.typePh\ ^C^C\Ph\^COOHC=—C\COOHhv--Ø,crystal p-truxinicacidPh COONCOOH4molecular displacement22,23,24 with the preservation of configuration from reactants toproducts. However, as opposed to the solid state reactions, the molecules in the isotropicmedia were found to undergo photoisomerization to the cis-form. From the studies ontrans-cinnamic acid and its derivatives, Schmidt reported an excellent illustration of thetopochemical principle. The trans-cinnamic acid compounds generally show three crystalmodifications, namely a, 13 and 7-types (Figure 2).18,19,22,24a-typePh \C—C\HOOC\^COONC\PhhvcrystalHOO COOHa-truxillicacid Phy-type^ /COONC^=CPh" COOHC^ C/Ph"hvcrystalno reactionCOOH^ /^hvsolutionPh/ Ph/^COONtrans^ cisFigure 2: Solid state photochemistry of the three crystal modifications of trans-cinnamicacid5As shown in Figure 2:a) In the a-type; the intermolecular center-to-center distance between theoverlapping double bonds of adjacent molecules is between 3.6-4.1 A, and theadjacent molecular pairs are related by a centrosymmetric anungement.b) In the 13-type; the adjacent molecules are parallel and slightly translated. Theneighboring olefinic double bonds have considerable face-to-face overlap with acenter-to-center distance of 3.9-4.1 A.c) In the y-type; the adjacent molecules are related by a translation but the doublebonds are offset in such a way that they do not overlap. The center-to-centerdistance between the double bonds is between 4.7-5.2 A.Irradiation of a-type and I3-type crystals caused a photochemical dimerizationreaction to yield centrosymmetric a-truxillic acids and mirror symmetric 13-truxinic acids,respectively, whereas 7-type crystals were found to be photostable.As a result of the above observations, Schmidt drew the following conclusions forsolid state [2+2] photocycloaddition reactions:a) The product formed is governed by the nature of the packing of theneighbouring molecules around the reactant rather than the intrinsic reactivity ofthe reactant.b) Proximity (<4.1 A) and a parallel alignment of the potentially reacting centersare crucial for the dimerization.c) Dimerization between nearest neighbor molecules occurs with a minimum ofmolecular and atomic movement.d) There is a direct correlation between the configuration and symmetry of theproducts and reactants in the solid state photodimerizations.6Therefore a knowledge of the closest neighbor disposition as well as thedetermination of the distance between double bonds could allow one to predict thegeometry of the products obtained by photoreaction. Photoreactive a and 13 type crystalmodifications have intermolecular distances of 3.6 to 4.1 A, and so dimerization shouldnot occur beyond this limit. Schmidt23 suggested an upper limit of 4.1 A for the distancebetween the reactive double bonds for a [2+2] photocycloaddition reaction. However, inthe case of m-bromo-cinnamic acid, in spite of a 3.9 A distance between the potentiallyreactive double bonds, irradiation does not lead to any photodimerization.25 Here thephotoinertness was suggested to be due to the non-parallel arrangement of the reactivedouble bonds, which leads to poor overlap between them. In the case of the photoreactivea and 13 crystal modifications, both distance and parallel alignment of double bond criteriaare satisfied, but they are not fulfilled by the y-modification,2426 where the large distance(4.7-5.1 A) and poor overlap between the double bonds makes them photostable.In recent years, these topochemical postulates have provided a landmark in organicsolid state photochemistry and have been used as rules to rationalize a large number of[2+2] photochemical dimeiization reactions of compounds with widely varying structures,such as the dimerization of fumaryl derivatives,27 butadiene derivatives,2829coumarins,30-34 and benzilidene cyclopentanones.35,36 An example for each case isshown in Figure 3.1.1.2. Non-topochemical Photodimerization.Although the majority of solid-state photodimerization reactions strictly follow thetopochemical rules, there are reports of dimerization reactions which deviate significantlyfrom the accepted topochemical postulates put forward by Schmidt. One example of suchbehaviour was observed by Ramamurthy et al. on coumarin derivatives.37 Irradiation of7-chlorocoumarin causes a [2+2] photodimerization reaction even though the distancebetween the reactive double bonds (4.5 A) exceeds Schmidt's proposed upper limit ofHOOC.,....e7/..HOOC.,,,,,,e.„,-coumarins:COOH^hv--",crystal..,7*COOH.7COOH(Ref. 28, 29)OMe ()meCOOHhv--,crystal(Ref. 33)Me0HOOCHOOhv--I.crystal^ X = H= Br(Ref. 35)benzilidenecyclopentanoneso74.2 A. Likewise, in 7-methoxycoumarin dimerization occurs in spite of the reactivedouble bonds being 65° with respect to each other with a center-to-center distance of 3.8A. The above exceptions indicate that a certain amount of flexibility is required inapplying these rules, depending on the system under investigation.fumaryl derivativesNC/CNC^ C/hv-6,crystal(Ref. 27)butadiene derivativesFigure 3: A few examples of solid state photodimerization.8Other examples of such non-topochemical photodimerizaion have been found forsome 9-cyanoanthracene derivatives,38 in which the type of products formed cannotalways be predicted from the X-ray structure of the starting materials. In the mid 1960s,Craig and Sarti-Fantoni,38 who first observed such non-topochemical dimerization,showed that these reactions take place at defects or surfaces or zones that are disordered.Schmidt and co-workers later investigated a series of anthracene derivatives and foundmany cases behaving in a non-topochemical fashion. 39,40 They have also shown thatanthracene derivatives crystallize in three different crystal modifications, a, 13 and y,having three different packing arrangements as depicted in Figure 4.Molecules in a-type crystals are packed in head-to-tail (centrosymmetric) fashionand upon irradiation become topochemically controlled head-to-tail dimers. In the 13-typecrystals, the molecules (R= Cl, CHO, CN) are arranged in a head-to-head (non-centrosymmetric) fashion, however, upon irradiation give head-to-tail photodimers insteadof the topochemically controlled head-to-head products. In both the a and 13-types theneighboring molecules are arranged in pairs with considerable overlap between them. Inthe a-type the C(9')--C(101) contacts between the neighboring molecules is less than 4.1A. In the 13-type the distances between the meso-carbons of the nearest neighboringmolecules are less than 4.1 A. Whereas in the y-type, the non-parallel alignment and largedistance (> 5 A) between the meso-atoms of the neighboring molecules makes themphotostable. Almost all 9-substituted anthracene molecules, upon irradiation hi solution,dimerize to yield only the head-to-tail dimers and not the head-to-head dimers. Fromthese results it can be concluded that head-to-head dimers are not a stable form.In crystals, dislocations and other defect sites are commonly present, but they arenot detectable by X-ray diffraction methods, which give the averaged structure of themolecules at regular sites. Since the number of molecules located at the defect sites isusually a small fraction of the molecules in the regular lattice sites, the photodimerizationshould be governed by the regular lattice sites. But in crystals where unusual9photochemical reactions are observed, the defect sites seem to govern the reaction, eventhough they are only present in small amounts.a-type:hv head-tail dimerR = Cl, Br, Me, CO2 Me, CONH2head-head arrangementR = CI, CHO, CN.mirror symmetric dimer7-typeno reactionR- OMe, Cl, CNFigure 4: Three crystal modifications of andracene derivatives.When crystals are irradiated three events can occur from the excited statemolecule: deactivation by radiative or radiationless processes, reaction (dimerization in the1 0present example) and transfer of excitation to another site. If we assume that thedeactivation process is independent of the nature of the site, then when energy is absorbedby molecules in a crystal the reaction takes place at the site where the absorptionoccurred. When the dimerization process is very slow, the process of transfer ofexcitation to a neighboring site has a higher probability of occurring. Since the normalsymmetry of the sites is disrupted at the dislocations, molecules at these sites are likely toact as trapping centers for excitation. It has been suggested38,41 that the excitationenergies of the anthracene molecules are slightly reduced when they are displaced from theregular lattice sites.Defect sites can therefore function as favoured areas for reaction. In other words,if the light energy can be transferred rapidly within the crystals after absorption, then thephotochemistry of the ideal lattice need not be important. Instead, photoreaction wouldbecome more probable in regions where excitation energy can preferentially migrate.Although the number of molecules at the defect sites is small, as the reaction progressesthe defect sites will multiply in order to give an appreciable yield of products.1.2. The Concept of the Reaction CavityTopochemical principles and defects can be used to rationalize chemical reactionsin the crystalline state, regardless of whether molecules in the lattice are suitably arrangedfor a reaction or not. However, in some examples, even though molecules in the latticeare favorably arranged for a chemical reaction, they remain photostable.42 To explain thisCohen43 introduced a new qualitative concept into the topochemical principle known asthe "Reaction Cavity".The cavity or the cage is the space in the crystal lattice occupied by the moleculeswhich are directly involved in the chemical reaction. This space, with well defineddimensions and shapes, is limited or governed by the contact surfaces of the internalmolecules with the surrounding molecules. Any molecular rearrangement or other1 1changes within the cavity during the process of a reaction can exert pressure on the cavitywall. In particular, the formation or removal of empty space within the cavity isenergetically unfavorable, since these involve great changes in attractive and repulsiveforces (Figure 5.). Therefore reactions that are controlled by the crystal lattice will occurwith minimum deformation of the reaction cavity.Figure 5: (1) Favorable and 2) unfavorable solid state reactions in the reaction cavity(transition state in dotted lines).The "Reaction Cavity" concept has become very useful in explaining thephotostability of several compounds where the molecules in the crystal are arranged(topochemically) ideally for photodimerization.42 Several examples of the unusualphotobehaviour of crystals which do not obey the topochemical postulates have beenreported from time to time, and a wide range of concepts has been put forward to providemore accurate information about the reaction cavity.McBride et a/.44 introduced the "local stress" concept to explain the mechanismsby which diacyl peroxides decompose in the solid state (Figure 6). Solid state irradiationof bis (3,3,3-triphenyl propanoyl) peroxide (1) was analyzed by ESR spectroscopy toidentify the phenyl group (all three phenyl groups are non-equivalent by virtue of theirdifferent environments in the anisotropic medium) of the neophenyl radical (2) whichmigrated in the solid state to give radical (3). An anisotropic "local stress", developed12inside the crystal lattice by a recently liberated carbon dioxide molecule, was postulated tobe the controlling factor in the selection and migration of the phenyl group. Moreover,the amount of stress was measured by FTIR, since a particular stretching frequency ofcarbon dioxide depends on pressure. It was suggested that the stress was transmitted toone side of the migration terminus, thus inclining the radical carbon in the oppositedirection, more towards the migrating phenyl group. By comparing the behaviour of avariety of diacyl peroxides, it was shown that stress is a more important factor in thesereactions than the topochemical postulate, including the shape of the cavity.0^0II IIPh3CCH2 —C-0 —0—C—CH2CPh3 hvcrystal-CO2PhPh —C-61-12 —I,. Ph—O—CHVPhI^IPh Ph(1)^(2)^(3)Figure 6: Photochemistry of a diacyl peroxide.Gavezzotti6,45 takes into account the volumes occupied by molecules and emptyspaces in the crystalline arrangement. He developed a quick and precise method tocalculate the volumes of the empty and filled spaces in the lattice. Packing densitydiagrams calculated from a computer program allowed him to locate the void zones orholes or channels in the crystal structure. Using these maps he analyzed a variety of solidstate reactions and concluded that a prerequisite for crystal reactivity is the availability offree space around the reaction site. The free spaces around the reacting partners, the sizeof which may vary from system to system, can favour reaction between less than ideallyoriented pairs.Scheffer, Trotter and co-workers46 took into account some specific stericinteractions between the reactant molecules and surrounding molecules that preventneighboringmoleculeNVVV\A.iioI^I,Me0neighboringmolecule(4)^(Ref. 46)13chemical reactivity in the solid state. They termed this effect "Steric CompressionControl". Compound (4) (Figure 7) undergoes unimolecular photorearrangement in thesolution state, but in the solid state, even though the reactive double bonds in theneighboring molecules are arranged in a topochemically favorable distance and orientation,the crystal remains photostable. It has been proposed that the unreactivity is related to thearrangement of the neighboring molecules in the crystal lattice. If the [2+2]photocycloaddition reaction were to proceed, the steric compression of the two methylgroups of the reacting molecules with those of the surrounding molecules would increase,and thereby prevent the photodimerization.Figure 7: Steric compression control of compound 4.A quantitative relationship between a solid state reaction rate and a crystal latticeparameter has been developed recently by Ohashi and co-workers.47,48 They investigatedseveral optically active cobaloxime complexes (5) (Figure 8) which undergo racemizationat the cyanoethyl chiral center upon the action of X-rays. Because of their single crystal-to-single crystal (topotactic) nature, these reactions could be followed by crystal structureanalysis (X-ray) of the reaction intermediates, and their relative rates determined. Theserates were then con-elated with the reaction cavity volumes, which were calculated from14the X-ray crystal structure data. It was found that the larger the reaction cavity, the fasterthe reaction rate.113 C.03.^CNHIPIN■C- X = (S) - NH 2CH(CH3)C6H5 [(R) -1-cyanoethyl]= (S) - NH 2CH(CH3)C6H5 [(S) -1 -cyanoethyl]= C5H5 N [(S) -1-cyanoethyl](5)Figure 8: Cobaloxime complexes used in the experiment.1.5. Unimolecular Reactions:As described earlier, the close proximity and proper alignment of the reactive sitesof neighboring molecules are important prerequisites for a successful bimolecularphotoreaction in the solid state. When these conditions are fulfilled, topochemicallycontrolled dimers are formed in which the intrinsic and relative geometries of the reactantsare preserved. Thus the intermolecular packing arrangements and the crystal latticeconstraints play an important role in controlling solid state bimolecular reactions. In thelast 30 years, studies of chemical reactions in the organic solid state have been concernedmainly with bimolecular processes. Correlation of the [2+2] photocyclization reactionswith X-ray crystal structure data has provided valuable insights into the requirements forfeasible reactions.15A major problem with studying bimolecular solid state reactions is theunpredictability of the preferred packing arrangement of organic molecules in crystals. Inunimolecular reactions (such as intramolecular hydrogen abstraction, electrocyclization,fragmentation reactions, etc.), conformational factors usually determine the success andthe type of the reaction, whereas intermolecular packing effects play only a secondaryrole. Therefore, X-ray crystal structure analysis provides an opportunity to study theintrinsic reactivity of a single conformer. Another advantage in dealing with unimolecularsolid state reactions is that the molecules that make up the crystal lattice are generallyfound in their lowest or near to their lowest energy conformations.49 Theseconformations, which may also be predicted using the principles of conformationalanalysis, provide a certain amount of information regarding possible unimolecular chemicalreactivity in advance.Unlike bimolecular reactions, the majority of unimolecular photorearrangementsproceed through relatively large conformational and configurational changes along thereaction coordinate. Favorable reaction pathways involving low energies of activation areoften observed in unrestricted systems, such as isotropic fluid media. But in the crystallinephase, because the molecular motions are limited by the external physical restraintsexerted by the lattice environment, and despite relatively high activation energies (in theisotropic medium), molecules tend to undergo alternate, less motion pathways to yieldtopochemically controlled products. These products are often different from the onesobserved in isotropic liquid media, where they are usually formed by a greater motionpathway. Solution products are often topochemically forbidden in the solid state, sincethe conformational changes required for their formation are too large to be permitted bythe constraints of the crystal lattice.Although sporadic reports on unimolecular photorearrangements are to be foundin the literature of the last 100 years, such medium-dependent unimolecularphotoreactivity has not been clearly explained owing to the absence of structural16information about the crystalline phase.50-53 At present, with the help of X-raycrystallography, which can accurately determine the structure as well as the environmentof the starting materials, solid state reactivity patterns can be rationalized by means ofstructure-reactivity correlation studies. Such studies provide a clear understanding of therange and nature of the motions of atoms permitted during the rearrangement process. Inmost solid state photorearrangements it is assumed that the intermediates and thetransition states in the reaction under study resemble the starting materials.In the last 20 years Scheffer and co-workers have made major contributions to thestudy of unimolecular photorearrangements in the solid state by using structure-reactivitycorrelations. They have systematically investigated a series of closely related systems(cyclohexenones54, ene-diones55, 13,7-unsaturated ketones56, aryl ketones57 and 1,4-dienes58) and have elucidated how the ground state conformations influence the excitedstate behaviour of these systems. Examples of the above systems are depicted in Figure 9.(a) PhPhPh(Ref. 55c)PhPhPhsolid state^ 100%^00%solution reaction 75% 25%hvcrystalhvsolutionOAc0hv_/,. Itosolution^0•de0 +,....„...^CO2CH3+CH302(c)17(Ref. 56)(d) hyOCH3+cis^ transsolid^60%^34%soution (C6 H6)^28% 72%(Ref. 57d)crystal^85%^small amounts^small amountssolution -50% -50%(Ref. 58E)Figure 9: Photochemistry of a) ene-diones, b) cyclohexenones, c) 13, 7-unsaturatedketones, d) arylketones and e) 1,4-dienes.1.4 Type II Reaction.The Type II reaction59,60,76,115 is the most commonly known and well studiedexample of a photochemically-induced intramolecular hydrogen abstraction reaction. AsbiradicalintermediateR'cyclization ^ R'HOcis+ Rh,^‘‘‘IlHO1---‘R.transCH2OHenol11CH2alkene18shown in Figure 10, upon irradiation the y-hydrogen atom of a ketone is abstracted by the(n,it*) excited carbonyl oxygen atom through a cyclic six membered transition state toproduce a 1,4-biradical intermediate. These biradical intermediates can cyclize tocyclobutanol derivatives (Yang reaction)61 or cleave (Norrish type 11)62 to an alkene andan enol (isolated as the ketone, but detectable spectroscopica1ly)63a or undergo reversehydrogen transfer to regenerate the starting materia1.63bFigure 10. Type II reaction.Photochemically-induced y-hydrogen abstraction reactions in aliphatic carbonylcompounds are known to involve both singlet and triplet (n-e) excited states,116 wherethe non-bonding orbital of the electron deficient oxygen atom in the excited carbonylgroup abstracts the y-hydrogen atom. Photochemically-induced y-hydrogen abstractionreactions have been widely investigated in the solid state in order to study the favoured57transition state geometries for hydrogen abstraction by the carbonyl chromophore.In solid state photochemical reactions, owing to the constraining crystallineenvironment, the possible transition state geometries for abstraction are limited toconformations which closely resemble the ground state reactant. Thus the X-ray crystalstructure of the reactant obtained prior to the reaction can provide valuable information19regarding the transition state geometric requirements for hydrogen abstraction. Using thisinformation, structure-reactivity correlations in solid state photochemical reactions can beinvestigated. Furthermore, since the probable conformations of the 1,4-biradicalintermediate of the reactions can be predicted from the X-ray crystal structures, we alsolearn the partitioning behaviour of the biradical intermediates to cyclization, cleavage anddispropotionation products.1.4.1. Geometrical Relationship for Hydrogen Abstraction.The preferred geometry for a successful 7-hydrogen abstraction in aconformationally mobile system was suggested by Wagner as a strain free chair-like sixmembered abstraction geometry.64 Houk et (11,65,66 from their force-field models and abinitio calculations, showed that the preference for regioselective hydrogen transferthrough a six-membered ring transition state (7-hydrogen abstraction) over a seven-membered (8-hydrogen abstraction) is the result of the favorable entropy of activation,rather than an unstrained chair-like transition state geometry.The geometrical relationship between the abstracting oxygen atom and thehydrogen atom being abstracted can be described by four parameters (d, 0, A and co), asshown in Figure 11.d = the distance in angstroms between hydrogen and oxygen, 0...H.co = the angle formed between the 0...H vector and its projection on the meanplane of the carbonyl group.= The C=0.-H angle.A = The C-1-1-0 angle.20e)*"..mil\CA^ ■•••••Figure 11: Geometrical parameters for the abstraction of a hydrogen atom by thecarbonyl oxygen atom.To find the optimum geometrical requirements for hydrogen abstraction, boththeoretical and experimental aspects have been investigated. On theoretical grounds, aninteratomic distance of 1.8 A has been proposed as the upper limit67 for the Type IIy-hydrogen abstraction. Djerassi and co-workers have also suggested an upper limit of1.8 A for d, based on their work on the McLafferty rearrangement of steroidal ketones.68Similarly, a distance of 2.1 A has been estimated for the well known Barton reaction for aseries of conformationally rigid steroid systems.69 In the above two cases, the estimate isbased on measurements obtained from molecular models.A few years ago Scheffer et al. studied a variety of ketones that undergointramolecular hydrogen transfer in the crystalline state, and obtained valuable informationregarding the geometrical parameters. In analyzing their reactivities, they considered theground state parameters of the reactant obtained from the X-ray structure. The solid statehydrogen abstraction distance was found to be much greater than had previously beenconsidered feasible. In an initial investigation of a series of ene-dione55 compounds, itwas found that the successful intramolecular hydrogen abstraction by oxygen occurredwith 0-•H contact distances less than or equal to 2.6 A. Based on these results hesuggested that hydrogen abstractions can occur over a distance that is less than or equal tothe sum of the van der Waals radii of the atoms involved70 (van der Waals radius ofoxygen = 1.52 A; hydrogen = 1.20 A).7133 Furthermore, his studies in the a-cycloalkyl-p-substituted acetophenone57f and a-adamantyl-p-substituted acetophenone57a-e series21(Figure 9d), which undergo Norrish Type II y-hydrogen abstractions, indicate that the2.7 A is not an absolute upper limit for hydrogen atom abstraction. Five out of theseventeen compounds studied had an abstraction distance greater than 2.7 A. Schefferalso pointed out that whenever the ground state geometrical relationship between theabstracting and the abstracted atoms is close to the ideal values (vide infra), minimalmolecular motion is required for reaction.The oxygen atom of the carbonyl group cannot abstract hydrogen with ease in alldirections, because the non-bonding orbital involved in the abstraction lies in the nodalplane of the it-bond. Therefore, a successful hydrogen abstraction is generally observedwhen the hydrogen atom approaches the carbonyl group in a way that allows it to havesubstantial overlap with the n-orbital of the oxygen atom. Almost two decades ago, Turrosuggested that, in the case of a hydrogen abstraction by a carbonyl group, the hydrogenatom should lie along the axis of the carbonyl non-bonding orbital (co = 00).72 Since thenseveral examples have been reported in which efficient intramolecular hydrogen transferhas taken place despite the developing 0—H bond having a fairly large co angle.64 Theabstraction is, however, expected to be more facile when co = 00; several examples reportno abstraction when co = 90°,74,77 but there are some exceptions. Efficient intermolecularhydrogen abstractions have been observed in the photochemistry of the solid complexes ofacetophenone and deoxycholic acid, even when co = 90°.75 It was suggested that themolecular motions within the crystal lattice permitted low values of co. Wagner76proposed a cos2c0 dependency of the abstraction rate on the dihedral angle associated withthe developing 0—H bond and the carbonyl nodal plane.Recently, the investigation of the preferred angular relationships for hydrogenabstraction (in the n,n* excited states) has been approached using semiempirical and abinitio computations, which have provided a firm theoretical foundation for this problem.Dorigo and Houk undertook ab initio studies on various systems in order to investigatethe geometric requirements for the intramolecular 'y-hydrogen abstraction of triplet22butanal.66 Their investigation revealed that large deviations from 0 =180° or co = 00values increase the AH# (enthalpy) dramatically.A linear arrangement of C—H-0 (0 = 1800) is thought to be preferred for afavorable abstraction, but several examples indicate that the angle 0 can vary significantlyfrom 180°.64,76,70,117 With regard to the C=0-..H angle A, since the singly occupied non-bonding orbitals are involved in the hydrogen abstraction, the best value is believed to varyfrom 90° to 1200,78 depending on the orbital hybridization. The theoretically idealvalues79 of these geometrical parameters for an efficient hydrogen abstraction by thecarbonyl oxygen are summarized in Figure 12.d (A)^co (0)^A (0)^0 (0)<2.7^0^90-120^180Figure 12: Theoretically ideal values of the geometrical parameters for hydrogenabstraction by the carbonyl oxygen.1.5. The Norrish Type I Reaction.Photochemically-induced reactions involving a-bond cleavage of saturated ketonesare termed Norrish type I reactions. Although photochemical a-cleavage reactions ofcyclic ketones were first observed by Ciamician and Silber80 at the beginning of thiscentury, it was thirty years before Norrish and co-workers initiated mechanisticstudies81,82a of these reactions, and referred to them as type I. These reactions werefound to take place through both singlet and triplet excited states.82b The radical pairformed during the primary a-cleavage process can undergo one or more reactions,depending on the electronic, structural and stereochemical properties of each transitionstate of the subsequent reactions and the conditions under which the reaction is carriedout. The most common reactions derived from the radical pair of a ketone are radicalrecombination, disproportionation and decarbonylation. In the case of saturated cyclicA!(c HAT— CH2CH2 co, RI(CH2)n—CH3—CO 4612p. I^•(C142)n —OH2cf==c)^•ROH(CI)—cH3 --•ROH '.''.C.*()R 0--0.I(C 112)n GH223ketones, the biradical intermediate formed from the ring cleavage generally undergoes oneor more intramolecular reactions, as illustrated in Figure 13.^ro^1 CH2 CHO(C H2)n— C I-12It^(CF12)n-l—CH=C1-12reclosure/'0^disproportionation0CH2 —C,1^22_0. 1(C H2)n—C H2 (CH)— l-L2biradicalintermediateIoI(CI-)n —cH2Figure 13: The a-cleavage processes (Nonish type I reaction) of cyclic ketones.Much mechanistic work has been done on cycloalkanones, and it has been directedparticularly at the effects of structure on the reactivity of n-n* singlet and triplet states.The results indicate that the triplet is more reactive than the singlet.83,84 However, incyclic ketones, the rate constant for a-cleavage increases with the relief of ring strain andthe presence of radical-stabilizing a-substituents.84 Photochemically-induced a-cleavagereactions of ketones are frequently observed in gas and liquid phases, but to ourknowledge a solid state reaction of this type has not been reported to date.241.6. Polymorphism and Solid-Solid Phase Transitions in CrystalsBy definition, polymorphism85 is the ability of a substance to crystallize in differentcrystal forms under various conditions. These crystal forms (also known as varieties orphases) correspond to different periodic arrangements of the constituent elements, such asatoms, molecules and ions. The conformation of a molecule is not necessarily constantfrom one polymorph to another, and different polymorphs may exhibit different molecularconformations. The existence of different conformers of the same molecule in differentpolymorphic modifications is termed "conformational polymorphism".86 Therefore, themolecular conformation observed in crystals is usually but not always necessarily the onewith the lowest energy. An important factor that determines the existence ofconformational polymorphism is concerned with the interplay between the crystal forces(intermolecular forces) and the molecular geometry (intramolecular forces). Polymorphsof a given compound differ in structure and physical properties, such as solubility, meltingpoint, density, hardness, crystal shape, optical and electrical properties, as generallyobserved in the crystals of two different compounds.Solid-solid transformation between the phases or the polymorphs can be achievedby variations in temperature or pressure, and this phenomenon is known as a "phasetransition" or "polymorphic transition"87. Polymorphs can be classified into enantiotropicand monotropic systems.88 During phase transitions an enantiotropic system may becomea monotropic and vice versa. Enantiotropic crystals have transition temperatures lowerthan their melting points, whereas, monotropic crystals theoretically should have transitiontemperature above the melting point. However, the absence of a transition point belowthe melting point cannot absolutely confirm a monotropic crystal, since the transition pointmay be found below room temperature or may not be observed owing to slow transition.The reversibility of phase transitions depends on the stability of the crystal lattice.A metastable form of a crystal may either persist for years or undergo spontaneoustransformation to the stable form. Mnyukh89 pointed out the necessity of crystal25imperfections, such as holes, dislocations or defects, to start phase transformations. Manyof the transformations he studied seem to occur or be initiated at crystal defects, where thearrangement of the molecules in the lattice is interrupted. It is, therefore, difficult toinitiate a phase transition in a single crystal without defects. He also suggested that whensuitable defects of the right size and shape are absent, or when their concentration is low,a crystal modification can sometimes be kept indefinitely at a temperature well outside itsnormal range of stability.Phase transitions are generally accompanied by the deformation of one structure toanother, involving the translational or rotational motions of molecules. In some cases, thebasic crystal lattice geometry and symmetry are preserved, but the molecules may berelated by simple rotations or conformational isomers. Some general examples, whichrepresent different modes of transitions, are depicted in Figure 14. 6 aFigure 14: Types of phase transitions.a) Phase transitions involving simple rotations of the molecules, without disruptionof the lattice geometry and symmetry.26b) The complex transition of molecules without a simple relationship between thelattices.c) The phase transition accompanying a conformational change, also known as"conformational polymorphism".d) The simple rotation of the molecules, changing the symmetry by increasing thelattice parameters (doubled).871.7. Conformational Analysis of Medium Sized Ring and MacrocyclicCompoundsThe ideas of conformational analysis are widely used in the interpretation ofchemical transformations and reaction mechanisms in modern chemistry. The stable chairform of cyclohexane, with its distinguishable substituents at axial and equatorial positions,was first demonstrated by Hassel et a/90,91 in 1943. Since then a remarkable developmentin the conformational analysis of aliphatic six membered ring systems has taken place,92,93although only during the last twenty years or so have the conformational arrangements ofthe larger cycloaLkane ring systems (containing ten or more members) and their simplederivatives been investigated.From their investigation of the properties of medium sized ring and macrocyclichydrocarbons, alcohols and ketones, Ruzicka and Prelog94,9514 showed that the meltingpoint versus ring size curve did not rise steadily, as with aliphatic hydrocarbons. Theyalso observed that several other physical and chemical properties of the compoundsdepended on the ring size.The conformational details controlling the physical and chemical properties of themedium sized ring and macrocyclic compounds were not clear until Dunitz96 (1961)demonstrated the unique conformation of the ten membered ring skeleton of cyclodecaneand a variety of its derivatives by X-ray diffraction (Figure 15). Dunitz concluded that theconformation of the ring skeleton common to these different ten membered cyclic27compounds must represent a potential energy minimum. Thus the conformationalproperties of the cyclic compounds seem to depend more on ring size than on thesubstituents or simple heteroatoms present in the ring.Figure 15: The solid state conformation of cis-1,6-diaminocyclodecane dihydrochloride.In 1918 Mohr first described the construction of "strain free" molecules by usingdiamond lattice templates. 97 The three dimensional carbon framework of the diamondmolecule was considered a unique way of extending the ideal tetrahedral carbon bondlengths, bond angles and dihedral angles infinitely in a chair-like manner. Thus anyconformation that is superimposable on the diamond lattice should retain a form of chairarrangement with a minimum of angle and torsional strain. Dale 98 in 1963 pointed outthat the solid state conformations of the ten membered ring derivatives closely follow thediamond lattice, as does the chair conformation of cyclohexane (Figure 16). This was abreakthrough in the conformational analysis of medium and large rings.Figure 16: The diamond lattice conformation of the ten membered carbon frame.28Dale qualitatively investigated a series of saturated cycloalkanes, using space-fillingmolecular models, in order to classify all strain-free conformations with ring sizes varyingfrom six to thirty.98,99 From his studies, Dale made two important conclusions:1) Only even membered carbon rings can have skeletons without torsional strain,i.e., any cyclic systems having an odd number of carbon atoms cannot fit on thediamond lattice arrangement, and hence cannot have a strain-freeconformation.2) No ring size between cyclohexane and cyclotetradecane can have a strain-freediamond lattice conformation.He found severe transannular hydrogen interactions within the medium size rings,(less than fourteen membered) due to the short contacts between the hydrogen atomspointing into the ring. According to his studies, a variety of molecular models ofcyclododecane without angle strain can be constructed; however, he suggested that inorder to avoid as much torsional strain and transannular interaction as possible theconfirmation of the twelve membered ring has to accommodate a non-diamond latticesquare conformation. Evidence to support his findings come from the non-diamond latticesquare solid state conformation of cyclododecane100 (Figure 17) and its derivatives.101Figure 17: The solid state conformation of cyclododecane.29In the case of the ten membered ring compound, cis-1,6-diaminocyclodecanedihydrochloride, its stable existence in the diamond lattice solid state conformation (Figure15)96 is rather surprising; however, it clearly indicates a compromise between angle strain,torsional strain and transannular repulsion. Dale also recognized that the fourteenmembered ring would be the first large ring to exist in a strain-free diamond latticeconformation (Figure 18). A typical feature of the majority of the strain-freeconformations of the medium and large rings is that there are four "corners" in theconformations, each consisting of carbon atoms that are flanked by two gauche C—Cbonds.Figure 18: Strain-free diamond lattice carbon frame of the fourteen membered ring.Dale noticed that the hydrogen atoms at the corner carbon atoms are directed awayfrom the ring. From his qualitative studies on cyclic compounds carrying gem-dimethylgroups (C14-C24) 102 and ketal derivatives,103 he concluded that the two geminalsubstituents would occupy the corner positions in order to avoid severe transannularinteractions. As shown in Figure 19, the two adjacent gauche bonds at the corner areflanked by bonds with anti-dihedral angles (+1800 -600 -60° +180°). The C—C bondsof the rest of the molecule are anti to one another.Dale's notation'04 of a ring conformation consists of a series of numbers withinbrackets, each number representing the number of bonds on each side between two corner30atoms. The sequence of numbers in the square brackets starts with the smaller number ofbonds between corner atoms, followed by the larger number. For example the diamondlattice rectangular conformation of cyclotetradecane is [3434].5^6^7*0^0^40—moss0_60o^1800Figure 19: The corner positions (*) of cyclic compounds.As experimentally demonstrated by Dunitz,96 the introduction of functional groupson the cycloalkane ring has little effect on the preferred conformations. The replacementof a methylene unit by a carbonyl group (sp2) or a heteroatom should reduce thetransannular H/H interactions existing in cycloalkanes, and consequently lead to astabilizing effect on the conformation. Generally, carbonyl substituents in medium andlarge rings are found a to the corner positions, but not at the comers.105, 118 Since themethylene group at the corner position is almost unhindered, the substitution of a cornermethylene group by a carbonyl group does not relieve any non-bonded interactions.Furthermore, the carbonyl oxygen atom at a corner position is eclipsed with two hydrogenatoms on the a and a' carbons, and this geometry is known105 to be higher in energy thanthe one where the oxygen atom is eclipsed with a methylene group and a hydrogen atom,as observed when the carbonyl is a to the corner atom.In large rings, many of the strain-free skeletons that can be constructed usingmodels are unstable owing to their having either more gauche bonds than the theoreticalminimum or structures that are too open and do not fill the space efficiently. Dale98a31suggested that in large rings, rectangular conformations will be reasonably stable, asopposed to square ones, because the square has a large hole in the centre and lacks thevan der Waals attraction for the hydrocarbon chain on the opposite side. He consideredthat the stable rectangular conformations would contain two long parallel chains linked bya pair of short chains containing two carbon atoms (C2 bridges) which would fill the spaceefficiently with substantial van der Waals attraction between them. X-ray structures106 ofseveral large membered rings have been reported to have conformations with two longparallel chains joined by four carbon segments. Dale concluded that only the 14, 18, 22,26 etc. membered rings or the (CH2 )4n+2 series can have this ideal rectangular, diamondlattice conformation [3x3x]. The (CH2)4n series can also have rectangular diamond latticeconformations, which would contain two long chains linked by C3 bridges [4x4x].According to Dale, however, the [4x4x] conformations of the (CH2)n series would preferto collapse to a non-diamond lattice [3x3x] rectangular conformation, in order to adoptbetter internal van der Waals contacts. Such compact but strained conformations arethought to be favoured for the (CH2)n series. A pictorial representation of the aboveeffect on sixteen membered ring is depicted in Figure 20.[4444] [3535]Figure 20: Transformation of the cyclohexadecane molecular conformation from square[4444] (diamond lattice) to a rectangular [3535] (joining the dotted lineswould lead to a non-diamond lattice arrangement).321.8. Objectives of Current ResearchThe present study is an extension of previous research work from our laboratoryon type II reactions in the solid state, with the aim of improving our knowledge of theempirical guidelines on hydrogen abstractability by the carbonyl oxygen.Our interest in macrocyclic diketones was triggered by the reported X-ray crystalstructure of cyclooctadecane-1,10-dione (6), an eighteen-membered ring diametricdiketone,107 in which four of the eight y-hydrogen atoms of the solid state conformationwere situated in what appeared to be an ideal geometry for abstraction by the carbonyloxygens. To begin the investigation, a series of nine diametric cyclic diketones, with ringsizes ranging from 10 to 26, and having the general structure depicted in Figure 21, weresynthesized108-112 and their X-ray crystal structures obtained. All diametric diketonesinvestigated were known compounds.113,114n = 4 (6), n =5 (7), n =6 (8 ), n =7 (9), n =8 (10),n =9 (11), n= 10 (12), n= 11 (13), n= 12 (14).Figure 21: Diametric diketones.Examining the X- ray crystal structures of these diketones revealed that, in eachcase at least one y-hydrogen atom had an intramolecular cyclic C=0---H contact of lessthan 3 A. This has been reported in the studies on a-cycloallcyl acetophenones and33a-adamantylacetophenones79 as being the highest tolerable distance for a feasiblehydrogen abstraction in the solid state. Furthermore, several other characteristicproperties of these cyclic diketones, such as high melting points, good quality crystals,solid-solid phase transitions above room temperature (in few examples) andconformational polymorphism (twenty-six membered ring diketone) prompted us toinvestigate their photochemical behaviour with multiple objectives.Our major goal was to investigate the type II reactions of these diketones, and toperform structure-reactivity correlation studies by examining the X-ray data, in order togain more knowledge of the preferred spatial relationship between the carbonyl oxygenand the abstracted 7-hydrogen atom for a successful abstraction. Knowing the limits ofsuch geometrical parameters, which are directly linked with the favoured geometrynecessary for the initial y-hydrogen abstraction, would serve as a useful guideline topredict the success of the type II reaction.Our second major goal was to study the partitioning of the biradical intermediatesinto products. A ketone molecule in a collision free medium can attain a variety ofconformations owing to C—C bond rotations. Since the most preferred orientation forhydrogen abstraction is the nodal plane of the carbonyl group, 7-hydrogen abstraction bythe excited ketone would afford biradical cisoid (iBR) as the initial biradical intermediate;however, iBR will soon equilibrate with other possible biradical conformations such aspre -cis (BRi), pre - trans (BR2) and transoid or anti (t-BR) as shown in Figure 22.59a, 60,115,116It is generally thought that efficient cleavage of the biradical intermediates requiresa parallel arrangement of the central bond with the singly occupied p-orbitals.115Therefore the transoid or anti t-BR biradical intermediate would exclusively giveelimination (cleavage) product, whereas the cisoid and gauche biradicals can lead to both34cyclization and cleavage products. However, the gauche or cisoid conformations aregenerally known to undergo mainly cyclization rather than cleavage.115Figure 22: a) Cisoid, b) gauche (pre-cis), c) gauche (pre-trans) and d) transoid or anticonformational arrangements of the biradical intermediates.Based on these considerations, we were interested in studying the effect of thecrystal lattice on product selectivity (cleavage:cyclization and cis:trans product ratios),which would be influenced by the rigid conformations of the 1,4-biradical intermediatesenforced by the solid state. The restricted mobility of the 1,4-biradical intermediate in theconstraining solid state medium may lead to the formation of topochemically controlledproducts. For comparison, product ratios in isotropic media were also explored, bysolution state irradiations carried out in hexanes.35Our third major goal was the investigation of the solid state photochemistry ofdiketones in which the basic structure is slightly modified. We synthesized a non-diametric sixteen-membered ring diketone, cyclohexadecane-1,8-dione (15), in which thetwo carbonyls are separated by six methylene groups on one side and eight on the other,so that the abstraction of two non-equivalent 7-hydrogen atoms present in theunsymmetric conformation would lead to regioisomeric pairs of cis, trans cyclobutanolderivatives and cleavage products. Through this, the regioselectivity of the solid statehydrogen abstraction can be investigated. A seventeen membered ring diketone,cycloheptadecane-1,9-dione (16) was also investigated, using a similar strategy.Another structural modification was achieved by substituting a-hydrogen atomswith methyl groups, with the idea of promoting Norrish type I processes in macrocyclicdiketones. As explained in the Introduction section, the initial step of the type I reactioninvolves a-bond cleavage, and so, by introducing alkyl groups at the a-carbon atom, thecarbon-carbon a bond can be weakened, since a-cleavage leads to a more stablesecondary biradical intermediate.The photoreactions of diketones were also investigated in zeolites (a collaborationwith Dr. V. Ramamurthy at Du Pont), where, interestingly, both Norrish type I and type IIreactions were observed.Our fourth major objective was the investigation of the solid-solid phase transitionsobserved in four diketones, primarily by photochemistry (at different temperatures),together with solid state NMR (13C NMR, deuterium wide line NMR), FTIR and DSCtechniques.MM2 calculations (energy minimization and steric energy calculations), of severaldiketones were also performed in order to determine the low energy conformations. Ourmain interest was directed towards finding any conformations having lower energy thanthe solid state conformation.(1) 03/Me0H/ CH2C12(CH2)3^(cI-I2)3 4^(2) Me2SIheptane H2/Na/Al20336CHAPTER II2.0. Synthesis of Starting Materials.The diametric diketones cyclodecane-1,6-dione (6) and cyclododecane-1,7-dione(7) were synthesized via ozonolysis (Figure 23) of the corresponding bicyclicolefins. 108,109,110 The precursor (17) for the synthesis of diketone (6) was purchasedfrom Aldrich Chemical Co., while for the preparation of diketone (7), the correspondingbicyclic olefin (20) was synthesized from cyclododecane-1,5,9-triene (18), as reported byDale et a!.110(1)03/Me01-1/ CH2Cl2(CI42)2^(C H2)2(2) Me2S(17)^ (6)Na/Al203heptane(18)^(19)(7)^ (20)Figure 23: Synthesis of the ten and twelve membered ring diketones via ozonolysis ofbicyclic olefins./ CO2C2H5(C142)11\CO2C2H5(1)tBuO -K4- I xylene^* (C142)9^( HA(2)H30+37Preparations of all other diketones were achieved by bimolecular cyclization oftheir corresponding diacyl derivatives (Figure 24). The 20 membered ring diketone (11)was synthesized by the Dieckmann condensation reaction112 using diethyl dodecanedioate(21) in the presence of potassium tert-butoxide. The diametric 14 membered (8), 16membered (9), 18-membered (10), 22-membered (12), 24-membered (13) and 26-membered (14) ring diketones were synthesized using Blomquist's high dilutiontechnique,111 which involves the bimolecular cyclization of the corresponding diaciddichlorides (22) in the presence of triethylamine.(21)^ (11)/COO(1) NEt3 / C6H6(CF12)n+2 ^■ (CI-12)n^(CH2)n + (C\coa^(2) KOH/Me0H(3) H20o/.7 NV\ other)n-1^I^I^(C1-12)n- 1±products(22)n =4 (8), n =5 (9), n =6 (10) ,^n = 3 (23)n =8 (12) , n =9 (13) , n= 10 (14)^n = 4 (24)Figure 24: Synthesis of diketones from diacyl derivatives.38All diacid dichlorides were made from their corresponding &acids, which werechlorinated with thionyl chloride.111 The yields of the diketones are summarized inTable 1. Although the yields are quite low because of the polymerization of the acidchlorides, they are comparable to the reported values.111,112 The purification of thediketones was successfully carried out by column chromatography and recrystallization,instead of the reported distillation or vacuum sublimation methods.111Table I: Percentage yields of diketones and y-pyrones .diketone (ring size) diketone (%) pyrone (%)10 - -12 - 5614 09 2116 28 <118 25 -20 14 -22 41 -24 19 -26 29 -A possible mechanism for the formation of diketones from diacid dichlorides isillustrated in Figure 25. In the presence of base, diacid dichlorides undergodehydrohalogenation to yield bifunctional ketenes (25).119 The bimolecular cyclization ofthe diketenes, followed by base hydrolysis and decarboxylation, leads to the final product.During this process tertiary amine acts as a dehydrohalogenating and condensing agent. 111Et3N C6H6(2)Et3N CsH6(1)/C =C=0(CI-)nO-==0(C1-12)„(C142)n+i039(25) (Ref. 119)(CF12)n+1Nc/^ 0 ./(CH2)r4TCH==.0^•^'i- C\0 4\ (CH2)n+1( °OK(4) KOH/Me0HI(CF12)n+10(C)n1OH(2), (3)-5\ (CH2)n —cH==0(Ref. 111, 120)^00(cH2)r4.1%\ CHO(CF-2)rio(6)0(CH2)n±i(CH2)n+i0- \H20 I (8)A(cHA+ 1 \ _ c*0<(CH2)n+ ,.0-CO2(7)(4), (5), (6), (7), (8)^■Figure 25: A possible mechanism for the formation of diketones.40As indicated in Table I, the percentage yields of the diketones drop dramatically atthe 14 membered ring diketone (8) (n=6), and approach zero in smaller rings. Theseresults may be due to an unexpected side reaction which leads to the formation of a by-product, tricyclic y-pyrone. During the synthesis of the fourteen membered ring diketone(8), large quantities of the by-product tricyclic y-pyrone (24) were obtained along with thediketone. When the twelve membered ring diketone (7) synthesis was attempted by thismethod, the corresponding tricyclic y-pyrone (23) was obtained exclusively. Synthesis ofthe ten membered ring diketone from adipoylchloiide gave neither the diketone nor thecorresponding y-pyrone; however, during the workup procedure, large quantities ofpolymeric material were formed. These polymeric materials were found to be soluble onlyin chloroform. A possible mechanism for the formation of y-pyrone is depicted inFigure 26.The competition between the intramolecular and intermolecular reactions of thediketene intermediate (25) may be mainly controlled by the following two factors:(1) the length of the diketene molecule (entropy factor).(2) the ring strain (enthalpy factor)When^the two ketene functionalities within a molecule are far apart, andtherefore the intramolecular cyclization is less favoured. In these cases, the intramolecularcyclization involves a large unfavorable entropy loss along with severe transannularinteractions, which are prominent in medium size rings. When n = 4, 5 and 6, thetransition states associated with intramolecular cyclization will have 5, 6 and 7 memberedrings respectively. In such cases the entropy loss during intramolecular cyclization ismuch lower than during their intermolecular reaction (ie. bringing two individualmolecules together);123 furthermore, the small rings are relatively unstrained compared tothe medium size rings, therefore intramolecular cyclization prevails.E t3N / C6H6AC=C=0^/ ^Et3N / C 6H6^(CH2)n ______•,.\ ^Ac-=c=o(Ref. 120, 121)IKOH/Me0H(CI-12)n-141i.7,.......,,,,,Et3N / C6H6(CF)-2^(C1-2)n-2^ (CH2)n-10C(C1-12)n-1OH-C%0(Ref. 122)it 0/N/4._____),\V\) -1^rik^(C^■-CO2)n-1r4.?1H20Aa) protonationb) loss of waterFigure 26: A possible mechanism for the formation of y-pyrones.Based on these arguments, the formation of symmetric tricyclic y-pyrones (whenn = 5, 6) could be rationalized as an intramolecular diketene cyclization, followed by theintermolecular dimerization of the cyclic a-keto ketenes. This eventually leads to theformation of tricyclic y-pyrone in the presence of base.42It is, however, both interesting to consider and necessary to explain the absence oftricyclic rpyrone during the synthesis of the ten membered ring diketone (6). Thisabsence can be explained by reference to the work of J. C. Sauer,121 who confirmed theformation of the a-keto ketene (26) from adipoyl chloride (n = 4) by trapping it withethanol at room temperature (Figure 27). When Sauer attempted to isolate this fivemembered cyclic a-keto-ketene (the postulated intermediate for the formation of thecorresponding rpyrone) from the final reaction mixture by distillation, the attempt failed,and instead large amounts of polymeric compounds were isolated./c Et3N / CEH6pi-12)2 R.T.ckc2HSOH1=c,Hso(25) (26)—^IIo CII^IInpolymerFigure 27: Fate of adipoylchloride at different experimental conditions.It has been suggested that the thermally unstable five membered keto-ketene opensup and undergoes polymerization at high temperatures. Since this five membered a-keto-ketene was not our target compound, reaction was never attempted at room temperatureto reconfirm the formation of the cc-keto-ketene. However, Sauer's observations clearlyexplain our experimental results, since the high temperature used during the reactionprevents the formation of the corresponding rpyrone. During the synthesis of the sixteen0(1) COCl2^■(2) HI7 H20n=3 or 4^yield 42%43membered ring diketone (n = 7), the final reaction mixture on GLC showed a trace of apeak corresponding to its pyrone (< 1%) (recognized only on its retention time relative tothat of diketone), but the compound could not be successfully isolated or characterized.Two other synthetic routes for the preparation of symmetrical tricyclic y-pyronesare known in the literature.1) Bimolecular condensation of eneamines (27) in the presence of phosgene.124(27)2)^Condensation of eneamines (27) with P-ketoesters (28) at elevatedtemperatures. 125,1260IIz.,C\OEt(CI-)n\\,--•o n = 3 or 4^yield 70%(27) (28)The spectral data for y-pyrone 23 correlate well with the reported126 values. Toour knowledge, the synthesis of y-pyrone 24 (obtained as a side product during thepreparation of the fourteen membered ring diketone) has not been reported in theliterature.44The non-diametric diketones cyclohexadecane-1,8-dione (15) and cycloheptadecane-1,9-dione (16) were synthesized by Blomquist's method, using two different diaciddichlorides as starting materials (Figure 28). The desired products were separated fromthe by-products (diametric diketones A and B) by column chromatography./COG!^/ COCI(CF12)n+2^+^(C E42)n, +2\ COCI^\ COCI(1) NEt / co6 ^. (CF,^(CH2),I,(2) KOH / Me0H(3) 1-12015 (n = 6, n' = 8)16 (n = 7, n' = 8)+^(01-(2)n^(CI-12)„^+^(cF)n,^(Cl-).A^BFigure 28: Synthesis of non-diametric diketones.Synthesis of the keto-alcohols 9-hydroxycyclohexadecanone (29) and 10-hydroxycyclooctadecanone (30) was achieved by the partial reduction of diketones 9 and 10 withsodium borohydride.127The tetramethylated (all cis) sixteen membered ring diketone, 2R*, 8S*, 10R*,16S*-tetramethylcyclohexadecane-1,9-clione (31) and the twenty four membered ring(CF-{2)n^(CI-)nn = 5, 9.ill HCH3I /KIDME(CI-12)n^(CH) +^otherproductsn = 5 (31)45diketone 2R*, 12S*, 14R*, 24S*-tetramethylcyclotetracosane-1,13-dione (32) wereprepared by the alkylation procedure reported for cyclohexanone,128 which treats amixture of diketone and methyl iodide (— 1:4 molar ratio) with potassium hydride (Figure29). The purification of the tetramethylated diketones was achieved by recrystallizationand high performance liquid chromatography (HPLC). The stereochemistry of thediketones was determined by X-ray crystallography.n = 9 (32)Figure 29: Methylation of diketones.(40c) (40t) (41)(CI-)n(42)hvC6H12(CI-12)n-2^(CI-12)n-2HOIIH(CI-12)n+146CHAPTER ILL3.0. Photochemistry of Medium and Macrocyclic Diketones thatUndergo Type II Reactions.The photochemistry of cycloalkanones with ring sizes ten membered and above iswell known for hydrogen abstraction reactions by carbonyl oxygen atoms.129-134. Uponirradiation in cyclohexane, these cyclic monoketones 34-39 are reported to undergomainly intramolecular y-hydrogen abstraction to afford varying amounts of cyclization 40cand 40t (Yang reaction)61 and cleavage 41 (Norrish type 11)62 products together withsmall amounts of the photoreduction product cyclic alcohol 42 depending on the ring size(Figure 30).130 Photolysis of cyclodecanone (33) in cyclohexane, however, exhibits aunique e-hydrogen abstraction to afford 9-decalol exclusively. 135,136 The productpercentages of the cycloalkanone photochemistry in cyclohexane, reported byK. H. Schulte-Elte et al 130 are shown in Table II.n = 6 (34)n = 7 (35)n = 8 (36)n = 9 (37)n = 10 (38)n = 11 (39) .Figure 30: Photolysis of monoketones in cyclohexane.47Table.!!: Product percentages from the irradiation of monoketones in cyclohexane.monoketone(ring size)cis-cyclo-butanol (%)trans-cyclo-butanol (%)cleavage (%) mono-cyclicalcohol (%)Unknownproducts (%)11 40 14 08 12 2612 64 11 08 07 1013 45 23 18 05 0914 39 12 30 <1 2015 17 11 52 <1 1416 13 09 58 <1 20Two notable observations can be seen in the above product distributions frommonoketones:(1) The fraction of cleavage products increases with ring size.(2) A stereoselective cyclization is observed in smaller rings.As described by Wagner,115 the above results clearly indicate that a competitionbetween the cyclization and cleavage processes accompanies a change in ring size. Thepreference for cleavage product formation and the loss of stereoselectivity in thecyclobutanol formation in the larger membered rings suggest that the 1,4-biradicalintermediate conformations can easily undergo conformational rearrangements in theisotropic medium to achieve the preferred orbital overlaps to afford cleavage product 41as well as both cyclobutanol stereoisomers. In smaller rings, however, suchconformational changes in the biradical intermediates may be restricted due tointramolecular structural considerations. The above variation in the product distributionsseems to reflect the ability of the ring to adopt various conformations which consequentlycontrol the partitioning of the biradical intermediates into products.In the solid state, because the molecules are restricted to a single conformation andtheir structure can be obtained by X-ray crystallography, the effect of ring size on the2 6 2^8.41141 4 3^1.0263E=4148803881848preferred solid state conformation can be determined along with the favorable hydrogenabstraction geometries and the effect of conformation on the partitioning of the biradicalintermediate into products. The carbonyl excitations of aliphatic ketones are generallyknown to associate with an elongation of the C=0 bond and pyramidalization at thecarbonyl carbon,231 and therefore the stereoelectronic dispositions of the y-hydrogenatoms with respect to the carbonyl oxygens in the excited molecules will be altered.However, the structure-reactivity correlation studies conducted in our laboratory on awide range of compounds indicate79 that the ground state geometrical parametersobtained from the X-ray structures provide valuable information regarding the reactivity ofthe molecules. Such analysis can not be successfully achieved with medium or large ringmonoketones, as most of them are either liquids or low melting solids at roomtemperature. Therefore, the diketones, having relatively high melting points and stablesolid state conformations, are recognized as ideal candidates for the above structure-reactivity correlation studies.As generally observed in aliphatic carbonyl compounds, all medium andmacrocyclic diketones investigated in our laboratory showed a broad, low-intensity UVabsorption maximum attributable to the n—nr* transition in the range of 270-290 nm, butmostly close to 280 nm. A UV-VIS absorption spectrum of 10-2 M diketone 9 (e = 41) incyclohexane, typical for all other diketones in this study, is shown in Figure 31.088 A THRESHOLD^8 810WL^OPD^WL^OFT^WI^DPO^WI.^OFD—Wave lengthFigure 31: A UV-VIS spectrum of 10-2 M diketone 9 in cyclohexane.493.1. Photochemistry of Diametric Diketones.Irradiations of all diametric diketones were carried out in the crystalline phase andas 104 M solutions in cyclohexane (for details see Experimental Section). All non-alkylated diketones underwent a smooth type II photoreaction, except the ten membereddiketone, cyclodecane-1,6-dione (6), which remained photostable in both media. The X-ray crystal structures of both alkylated and non-alkylated diketones reveal that at least oneof the y-hydrogen atoms in each compound is located in a position favorable forabstraction by the carbonyl oxygen. Interestingly, however, the alkylated diketonesafforded only Norrish type I photoproducts and will be discussed later in chapter V. Asoutlined in Figure 32, the irradiation of the diketones to low conversions (10-15%) led tothree major photoproduct types; a cis-cyclobutanol derivative, a trans-cyclobutanolderivative, and the cleavage product ene-dione.Low conversions were maintained for all diketones in order to avoid anysecondary photoreactions from the reactive carbonyls in the photoproducts and also toavoid any serious damage to the lattice of the original crystals. In accordance withcustom138, cis-cyclobutanol here refers to the isomer in which the hydroxyl and thehydrogen atom at the ring junction are cis to each other, and trans-cyclobutanol refers tothe isomer where the hydroxyl and the hydrogen atom at the ring junction are trans to oneanother.All photoreactions were monitored and analyzed by gas-liquid chromatography(GLC) using a DB-17 capillary column. As observed by several others138,139, the cis-cyclobutanol derivatives have longer retention times than their correspondingdiastereoisomeric trans-cyclobutanol derivatives; however, cleavage product ene-dioneshave the shortest retention time. The major photoproducts formed in all cases wereisolated by column chromatography and fully characterized, except the cis-cyclobutanolderivative 10c from the eighteen membered diketone 10, which could never be separatedfrom the reaction mixture, and could only be identified by its relative GLC retention time.0^ Hhv^O(CH2)n (CH2)n --• (CH2)n (CH2)n.2HO^ HO-■.-.11110. (CH2)n (CH2)n.2 +^(CH2)no/\ A(CH2)n+2^(CH2)ndiketone biradicalintermediate cis trans ene-dione7e8e9e10e11e12e13e14e n = 3 7n = 4 8n = 5 9n = 6 10n = 7 11n = 8 12n = 9 13n=10 147c8c9c10c11c12c13c14c7t8t9t10t11t12t13t14tLltc)Figure 32: Photolysis of diketones in cyclohexane.51In column chromatography, the cleavage product ene-dione was eluted first,followed by the trans-cyclobutanol derivative and finally the cis-cyclobutanol derivative.The unreacted starting materials invariably had the longest retention times on the GLC,but were eluted first in column chromatography. The above elution orders in both theGLC and the column chromatography are general for all diketones investigated.3.1.1. Structural Determination of the Photoproducts.The cyclobutanol ring junction stereochemistry assignment could not bedetermined by 1H nmr, as the methine protons are masked by the methylene protons, butwas accomplished by obtaining the X-ray crystal structures of the photoproducts cis-cyclobutanol derivative 9c and trans-cyclobutanol derivative lit. With the knownconfigurations of 9c and lit, the 13C num and attached proton test (APT)140 correlationsenabled the stereochemical assignments of the cyclobutanol photoproducts from otherdiketones to be made. The methine carbon at the ring junction of the cis-cyclobutanols,identified by the APT, appears at 48.6 - 50.1 ppm, whereas the analogous signal for thetrans-cyclobutanol is shifted upfield to 40.4 - 43.7 ppm. These chemical shift differenceshave been observed in all cis/trans pairs, as indicated in Table III, and this trend appears tobe general.The chemical shift difference between cis and trans-cyclobutanol derivatives (M)from the fourteen membered ring diketone 8 is close to 9 ppm; however, smaller valuesfor M are observed in the larger membered rings, as shown in the Table III. Stericcompressions between the 13C carbon atom and a 7-carbon atom at the gauche positionare generally known to lower the chemical shift.141 As indicated in Figure 33, similargauche interactions by the 7-methylene groups in the larger ring of the cyclobutanol52derivatives may account for the chemical shift differences observed for the bridgeheadmethine carbon atoms of the cis and trans-cyclobutanol derivatives.Methine carbon chemical shifts of the cyclobutanol derivatives.Chemical shift in benzene (ppm)DIKETONE(ring size)cis-CYCLOBUTANOLtrans -CYCLOBUTANOLAS12 48.6 - -14 49.2 40.4 8.816 49.8 41.6 8.218 42.2 -20 50.1 43.1 7.022 49.5 43.4 6.124 50.1 43.5 6.626 50.1 43.7 6.4A careful analysis of the molecular models of the cyclobutanol photoproductsreveals that in the minimum energy conformation of the trans-cyclobutanol derivatives,both 7-methylenes of the methine carbon atom tend to be located at the gauche or close togauche positions, especially when the ring size is smaller.With the increase in ring size, the 7-methylenes tend to be located farther awayfrom the gauche positions. The gradual increase in the chemical shift of the methinecarbon atom of the trans-cyclobutanol with increasing ring size is evidence of thisobservation. In the case of the cis-cyclobutanol derivatives, however, these interactionsseem to be smaller than their corresponding diastereoisomers, irrespective of the ring size.Further evidence to support this argument comes from the X-ray crystal structures of thecis-cyclobutanol derivative 9c and the trans-cyclobutanol derivative lit. In the case of9c, one 7-methylene is at the anti position to the methine carbon atom, and the otherOH......--' p H2)n7CCIS53y-methylene is quite far away from the gauche position (torsional angle close to 120°). Incase of the trans-cyclobutanol lit, although the ring size is larger than for 9c, both y-methylenes are at gauche positions. Therefore, the larger y-gauche steric compressions inthe trans-cyclobutanol derivatives, when compared to those of the corresponding cis-cyclobutanol derivatives, correctly account for the lower chemical shift of the former. Thegradual decrease in the AS ppm values and the increase in the chemical shift values thataccompany the increase in ring size suggest that the larger the ring size, the smaller theeffect.TRANSFigure 33: Newman projection of cis and trans-cyclobutanol derivatives down the ringjunction.The mass spectra of both cis and trans-cyclobutanol derivatives show a fragmentat m/e (M-28), corresponding to the loss of an ethylene group by a [2+2] cycloreversionof the cyclobutanol ring. The signal corresponding to this fragment, although quite weakcompared to the base peak found in all cyclobutanol photoproducts, is evidence ofcyclobutanol formation.54The ene-dione cleavage products were characterized mainly by the 1H nmr patternof the vinyl end of the molecule. The spectrum in Figure 34b corresponds to the-CH2-CH=CH2 moiety of compound 13e, which is typical for all cleavage productsisolated. The spectrum, decoupled at 2.01 ppm (Figure 34c), simplifies the peak at 8 =5.75-5.85 ppm to a doublet of doublets. The coupling constants J = 10 Hz and 18 Hzdenote the cis and trans coupling of Hx by HA and Hs respectively. 141 Therefore the peakat 8 = 5.75-5.85 ppm attributable to Hx, a doublet of doublet of triplets (J = 18,10 and 7Hz), is the result of coupling by HB, HA and HD protons, as represented in Figure 34a.The peaks at 8 = 4.90 ppm and 5 = 4.95 ppm in the spectra, decoupled at 5.79 ppm(Figure 34d), are attributable to HA and Hs respectively. The observed small splitting ofthese peaks would be the result of geminal coupling between HA and HB and the long-range coupling by HD methylene protons. The two doublets in Figure 34b, attributable toHA (8 = 4.90 ppm, J = 10 Hz) and Hs (8 = 4.95 ppm, J=18 Hz), are therefore the result ofcis and trans coupling by Hx respectively. The peak at 8 = 2.0 ppm (JDx - JDE = 7 Hz),corresponding to the methylene protons HD, is two overlapping triplets.3.1.2. Photochemistry of non-diametric diketones.Photolysis of two non-diametric diketones, the sixteen membered ring diketone 15and the seventeen membered ring diketone 16, in cyclohexane afforded a complex mixtureof six type II photoproducts, as indicated in Figure 35. The unequal lengths of themethylene chains on either side of the two carbonyl functionalities lead to two non-equivalent 7 positions in the molecule, and thus the abstraction of the non-equivalent7-hydrogen atoms affords regioisomeric pairs of cis-cyclobutanol derivatives, trans-cyclobutanol derivatives and ene-dione cleavage products. The cis-cyclobutanolregioisomers (15c1 and 15c2) from the sixteen membered ring diketone were isolated bycolumn chromatography as solids.HE^/—Hx^HE HxJBX = 18 HzHB55(b)1Z--/ NI/ 1211  3 311  2 1JL_.331(c) JBX = 18 H..%JAB = 10 Hz (d)6 . 0^5.5^5. 0^4.5^2.0Figure 34:^(a) splitting pattern of the ally! moiety of ene-dione 13e.(b) 1H nmr spectrum of allyl moiety of ene-dione 13e.(c) spectrum decoupled at 8 2.01.(d) spectrum decoupled at 8 5.79.56n = 6, n' = 8 (15)n = 7, n' = 8 (16)Ihvon = 6, n' = 8 (15c2) n = 6, n' = 8 (15c1)n = 7, n' = 8 (16c2) n = 7, n' = 8 (16c1)(C142)n-2 (CNA' +^(CH)n (CH2)n._2n = 6, n' = 8 (15t2)^n = 6, n' = 8 (15t1)n = 7, n' = 8 (16t2) n = 7, n' = 8 (16t1)H^(CIA-1 (CH)Y+2 CH3\/ y yC H2^0^0(CFL2)n+2 PH2)n.-1^H4.^Y Y0^01_12n = 6, n' =n = 7, n' =8 (15e2) n = 6, n' = 8 (15e1)8 (16e2) n = 7, n' = 8 (16e1)Figure 35: Photolysis of non -diametric diketones.57Even though the stereochemistry at the ring junction was confirmed from the 13Cnmr chemical shift values of the methine carbon atoms, the regiochemistry of the productswas determined by X-ray crystallography in both cases. The other photoproducts fromthe sixteen membered diketone, as well as those from the seventeen membered ringdiketone, were isolated and identified as a mixture of regioisomeric pairs. The productratios obtained in the solid state photolysis of the seventeen membered ring diketone 16were quite similar to those obtained in solution. However, the solid state reaction ofdiketone 15 afforded the cis-cyclobutanol derivative 15cl almost exclusively. With theexception of 15c1 and 15c2, all the other products gave rise to a single peak on GLC foreach regeoisomeric pair, and their relative proportions could therefore not be determined.3.1.3. Photochemistry of cyclic keto-alcohols.The sixteen membered ring keto-alcohol 9-hydroxycyclohexadecane-1-one (29)and the eighteen membered ring keto-alcohol 10-hydroxy cyclooctadecane- 1-one (30)were irradiated as crystalline solids and in cyclohexane. The photoproducts could not beseparated and characterized, but were identified to a certain extent by comparing the GLCretention times with those of the authentic samples made from the photoproducts of thesixteen and eighteen membered ring diketones 9 and 10.As indicated in Figure 36, type II reactions of keto-alcohols can lead to fivephotoproducts. The irradiation of keto-alcohol 29 led to the development of five newpeaks on GLC (DB 17, 190 °C); peak retention times and the corresponding amounts inparenthesis are given below.solid state reaction : RT's 4.5 (32%), 8.7 (22%), 8.8 (18%), 9.2 (18%) 9.5 (10%) min.solution reaction :^RT's 4.5 (40%), 8.7 (15%), 8.8 (20%), 9.2 (17%) 9.5 (8%) min.n = 5 (29t)n = 6 (30t)(CI42)n-1^(CF)2 CI-13XH OHn = 5 (29e)n = 6 (30e)OH^ HO(CH2)n (01-12) _2HOn = 5 (29c)n = 6 (30c)58(CI-)n^(CI-)ncJ^n = 5 (29)n = 6 (30)H OHFigure 36: Photolysis of keto-alcohols.The reduction of 9c (the cis-cyclobutanol photoproduct from diketone 9) withsodium borohydride gave two peaks on GLC (DB 17, 190 °C), which were identical to59those observed at RT's 9.2 and 9.5 min (in terms of their retention times). These twophotoproducts of 29 were assumed to be the diastereoisomers of cis-bicyclo[12.2.0]-hexadecane-6,12-diol (29c). Likewise, the reduction of 9t (the trans -cyclobutanolphotoproduct from diketone 9) gave two peaks that were identical to those at RT's 8.7and 8.8 min, and were assumed to be the diastereoisomers of trans-bicyclo[12.2.0]hexadecane-6,12-diol (29t). The above observations were also confirmed by co-injectingthe photoreaction mixture with the reduction products on GLC. The relative position ofthe peak at RT 4.55 min with respect to the cyclobutanol photoproducts is comparable tothe usual location of the cleavage products in other diketones, so this peak could belongto the cleavage product hexadecane-18-ene-2,10-diol (29e).In the case of the cyclic keto-alcohol 30, however, the irradiations in both mediashowed only three new peaks on GLC, at RTs 5.0, 9.1 and 10.2 min. Product ratioscould not be calculated from the GLC traces, since the peak at 10.2 min overlaps with theunreacted starting material, but after the removal of the unreacted starting material fromthe final reaction mixture by column chromatography, the product ratios were determinedand are given below in parentheses with their corresponding retention times.solid state reaction : RT's 5.0 (33%), 9.1 (59%), 10.2 (08%).solution reaction :^RT's 5.0 (56%), 9.1 (32%), 10.2 (12%).The reduction of 10t (the trans-cyclobutanol from diketone 10) with sodiumborohydride gave a single peak at RT 9.1 min. The co-injection of the photoreactionmixture and the reduction product increases the intensity of the peak observed atRT 9.1 min. This clearly indicates that the peak at 9.1 min corresponds to the twodiastereoisomers of the trans-cyclobutanol photoproduct, trans-bicyclo[14.2.0]-octadecane-1,10-diol (30t). The peaks at RTs 5.0 and 10.2 min could not be analyzed byco-injection experiments, but from the retention times of these two peaks relative to thatof trans-cyclobutanol photoproduct, one can assume them to be the peaks belonging tothe cleavage product ene-diol 10-hydroxy-hexadecane-10-ene-2-one (30e) and the60diastereomers of cis-cyclobutanol derivative cis-bicyclof14.2.0]octadecane-1,10-diol(30c), respectively. The X-ray crystal structures of both keto-alcohols 29 and 30 couldnot be obtained due to the poor crystal quality.The product ratios calculated (at 20°C) from GLC at various time intervals wereplotted as a function of conversion for all ketones studied. The ratios obtained byextrapolating the plots to zero percent conversion and normalizing to 100% are compiledin Table IV.The following important observations are apparent from Table IV:1) The proportion of type II cyclization (Yang reaction) is greater in the solid statethan in solution, except for the fourteen and seventeen membered ring diketones, wherethe product ratios are independent of the medium and found to be quite similar in bothmedia.2) In most cases, the stereoselectivity of the cyclobutanol formation increases inthe solid state compared to solution. Interestingly, with each two-carbon increment ofring size, the stereochemistry of the major solid state photoproduct changes, with theexception of the fourteen and twenty six membered (plates) (14P) membered rings.3) In solution, both a greater degree of type II cleavage products and thepreference for the formation of the presumably less strained trans-cyclobutanol over cis-cyclobutano1162 are observed in rings larger than fourteen membered.4) In the case of the twelve membered ring diketone, the cis-cyclobutanolderivative is stereoselectively formed as the major product in both media. A similarpreference for cis-cyclobutanol in both media is observed from the fourteen memberedring diketone 8; however the stereoselectivity is significantly lowered.5) The two crystal modifications of the twenty six membered ring diketone plates(14P) and needles (14N) stereoselectively afforded cis-cyclobutanol derivative 14c andtrans-cyclobutanol derivative 14t respectively.61Table IV: Product percentages at zero percent conversion obtained at 20°C.DIKETONE SOLID STATE SOLUTION STATE(ring size) cis (%) trans(%) cleavage(%) cis(%) trans(%) cleavage(%)diketones12 99 00 <01 84 00 1614 58 29 13 65 25 1016 89 10 01 22 35 4318 03 84 13 17 42 4120 90 04 06 10 23 6722 04 91 05 10 34 5624 98 01 01 15 27 5826needle 09 91 00 14 33 5326plates 97 03 00 14 33 53non-diametric cyclic diketones16*15d^15c200 0015c1^15c235 3998^02 13^1317 26 23 51 25 28 47cyclic keto-alcohols16 28 40 32 25 35 4018 08 59 33 12 32 5616* - Non-diametric sixteen membered ring diketone.To aid in their solid state conformational analysis, X-ray crystal structures of alldiketones, except that of the eighteen membered ring diketone cyclooctadecane-1,10-dione (10), were determined. The crystal structure of the eighteen membered ring62diketone was reported earlier by Allinger et al.107 The solid state conformation of the tenmembered ring diketone 6 (Figure 52) was also reported by G. Germain in a personalcommunication to J. Dunitz 143 almost 20 years ago. However, to our knowledge, the X-ray structure details have never been published. In the case of the twelve membered ringdiketone, the X-ray crystal structure could not be refined owing to the molecular disorderobserved in the crystal lattice; however, the preliminary studies indicate a basic square[3333] conformation with both carbonyls at non-corner positions pointing towards thesame side of the ring (the conformation shown in Figure 37a is generated by MM2). Lowenergy conformations of the ten, twelve and fourteen membered ring diketones (seeExperimental Section for details) were generated by MM2. The force field calculations ofdiketones with a ring size larger than fourteen membered were impractical, owing to thelength of cpu time required on a shared computer. However, for the 16 membered ringdiketone, a limited search generated possible low energy conformations.3.2. Diketones That Give Cis-cyclobutanols As The Major PhotoproductsIn The Solid State.3.2.1. Solid State Conformation and Photochemistry.As indicated in Table IV, the twelve membered ring diketone 7, sixteen memberedring diketone 9, non-diametric sixteen membered ring diketone 15, twenty membered ringdiketone 11, and twenty six membered ring diketone (plate crystals) 14P stereoselectivelygave cis-cyclobutanol derivatives as major solid state products. The solid stateconformations of these diketones are depicted in Figure 37.A common feature observed in the solid state conformations of this group ofdiketones is the [3x3x] carbon frame. Interestingly, with the exception of the twenty sixmembered ring plates 14P, the others belong to (CH2)4n series, and as suggested by Dale63for cycloalkanes,98a they prefer to crystallize in non-diamond lattice rectangularconformations rather than in diamond lattice [4x4x] conformations. However, Dale'squalitative analysis of the sixteen membered ring diketone predicts the [4444] squarearrangement for the solid state conformation.103 On the other hand, plate crystals ofdiketone 14P, which belongs to the (CH 2)4n+2 series, crystallize with their carbon atomsarranged in a diamond lattice frame. It seems that the orientation of the two carbonyls inthe solid state conformation is determined by the number of methylene groups separatingthem. When the number is odd the carbonyl groups are syn to one another, and when it iseven they are anti. The carbonyls of all compounds belonging to this group are in theshort segments of the rectangular conformations, a to the corner atoms, hence the ymethylenes and the carbonyl are placed in gauche positions (ideal for type II reactions),rather than in anti positions.K2H(e)C3H7Nb•HISHIHiHIOHI)Ht4HISHMI1419(f)64(c)Figure 37: Solid state conformations of (a) twelve membered (MM2), (b) sixteenmembered, (c) sixteen membered (non-diametric), (d) twenty membered, (e)twenty-four membered and (0 twenty-six membered ring diketones. (the y-hydrogen atoms with short 0....H contacts (d < 2.79 A) are indicated bydotted lines).653.2.2 Hydrogen Abstraction Geometry and Biradical Geometry.In each conformation, the two pairs of symmetry-related y-hydrogens accessible tothe carbonyl oxygens can be considered for analyzing the solid state photoreactivity of thediketones. One of these two pairs of y-hydrogen atoms has short 0...H contacts (d <2.76A) with the carbonyl oxygen, and forms a boat-like six-membered abstraction geometry.The other pair makes a chair-like abstraction geometry; however, their 0...-H contactdistances are generally close to 3A. In the case of the twelve membered ring diketone 7,only one pair (H6 and H16) of such y-hydrogen atoms is present and each hydrogen atommakes short contacts with both carbonyl oxygen atoms. The y-hydrogen atom H6 hasshort contacts with the carbonyl oxygen atoms 01 (d = 2.73 A) and 02 (d = 2.82 A) andmakes boat-like and chair-like abstraction geometries, respectively. The 0...H contactdistances and the abstraction geometries of the other y-hydrogen atom H16 with the 01and 02 carbonyl oxygens are reversed. A pictorial representation of the two types ofabstraction geometries (which are general for all diketones belonging to this group) andtheir Newman projections down the C2-C3 bond are given in Figure 38. The distance andthe angular parameters of the y-hydrogens are given in Table V. H(1) (2)Figure 38: (a) 1) Newman projection down the C2-C3 carbon-carbon bond (boat-likeabstraction geometry).2) Pictorial representation of boat-like hydrogen abstraction geometry.66(1)^(2)(b) 1) Newman projection down the C2-C3 carbon-carbon bond (chair-likeabstraction geometry).2) Pictorial representation of chair-like hydrogen abstraction geometry.As described earlier in the Introduction, the distance and angular relationshipsbetween the abstracting carbonyl oxygen atom and the 7-hydrogen atom to be abstractedare important for a successful abstraction. A careful inspection of the geometricalparameters reveals that at least one 7-hydrogen atom in each diketone is situated within2.76 A of a carbonyl oxygen with angles co, A, and 0 within the ranges of 50.4-63.8°,77.9-84.2° and 113.1-117.5°, respectively. The 7-hydrogen atoms with close 0....Hcontacts are indicated in Figure 37 by dotted lines. Although these values deviate slightlyfrom the suggested ideal values,79 several examples of successful hydrogen abstractions inthese ranges, through boat-like rather than chair-like six-membered abstractiongeometries, have been reported from our laboratory on a-cycloalkyl-p-chloroacetophenones144 Not surprisingly, therefore, 7-hydrogen atoms with the abovegeometrical parameters would be subject to smooth hydrogen abstraction.A key assumption in the solid state structure-reactivity correlation studies is thatthe initially formed 1,4-biradical intermediate has the same basic geometry in the solidstate as its ketonic precursor. In the solid state, any large changes in the molecularconformation are energetically disfavored by the constraining lattice medium; these67restrictions, together with the reported short life of the biradical intermediates, 145-148support the above key assumption.Table V: The geometrical parameters of the y-hydrogen atoms.DIKETONE(RING SIZE)y-hydrogenabstractedabstractingoxygend (A) co (°) A (°) 0 (°) abstractiongeometry12 H6 01 2.80 66.3 74.2 116.7 CHAIRH6 02 2.73 63.8 77.9 113.4 BOATH16 02 2.80 66.4 74.2 116.7 CHAIRH16 01 2.73 63.8 77.9 113.4 BOAT16 H6 01 2.74 53.2 81.6 115.4 BOAT1110 02 2.92 60.2 65.9 117.5 CHAIRH20 02 2.79 53.4 81.7 111.1 BOATH24 01 2.92 60.1 65.5 116.0 CHAIR20 H5 01 2.70 51.7 82.5 114.8 BOAT1413 02 3.00 59.1 63.0 114.4 CHAIRH23 02 2.70 52.1 84.2 114.8 BOATH31 01 2.99 59.7 63.9 115.4 CHAIR24 H5 01 3.12 56.1 59.1 115.2 CHAIRH17 02 2.69 49.6 84.0 116.4 BOATH27 02 3.17 55.0 57.0 115.5 CHAIRH39 01 2.67 50.4 83.2 117.5 BOAT26P H5 (1130) 01(02) 3.30 51.7 52.8 114.8 CHAIR1120 (H43) 02(01) 2.76 52.0 82.1 113.1 BOAT16* H6 01 2.99 59.0 65.5 116.6 CHAIRH10 01 2.72 53.3 81.4 115.7 BOAT16* - non-diametric sixteen membered ring diketone.The representation of the possible biradical intermediate for the sixteen memberedring diketone and its reaction center depicted in Figure 39 are typical for all other68diketones in this group. The singly occupied orbitals in the initially formed biradicals(iBR) are not orthogonal to each other as is generally assumed for non-cyclic allcanones.However, in the gauche 1,4-biradical intermediate, the abstracting oxygen atom at Cl andthe unabstracted 7-hydrogen atom at C4 would be in a "syn" relationship to one another(pre-cis biradical intermediate).3.2.3 Structure Reactivity Correlation.As shown in Figure 39, the biradical intermediate has four modes of closure to givecyclobutanol. Biradical closure through the least motion route "path a", or the largestmotion route "path d", would lead to a cis-cyclobutanol derivative, whereas "path b" or"path c" would lead to a trans-cyclobutanol derivative.NdFigure 39: a) Pre-cis biradical intermediate of diketone 9. b) Biradical intermediatereaction center69Since the biradical closure to products is likely to be topochemically controlled inthe solid state, the least motion closure through "path a" would be expected to befavoured and lead to cis-cyclobutanol derivative. Indeed, from this group of diketones, asshown in Table IV, cis-cyclobutanol derivatives were stereoselectively and almostexclusively obtained in the solid-state. Since the fate of the biradicals depends upon thethe flexibility of the reaction cavity and its free volume, the observed stereoselectivity inthis group of diketones suggests that the reaction cavity is very stiff, and indicates that the1,4-biradical intermediate surrounded by the ground state ketone molecules remains inalmost the same conformation as in the original crystal.The preference for cis-cyclobutanol formation in the solid state photochemistry ofthe diketones in this group can be related to the geometry of the biradical intermediate.Therefore, an examination of the diketone solid state conformation can provide valuableinformation regarding the preferred stereochemistry of the major cyclobutanolphotoproduct. Interestingly, in this group of diketones, the abstraction of any of the fouraccessible 7-hydrogen atoms would generate a pre -cis biradical intermediate, irrespectiveof which hydrogen atom is abstracted, and the least motion closure would eventually leadto cis-cyclobutanol derivatives. Since a successful hydrogen abstraction depends to aconsiderable extent on the 0-..-H contact distance,60 in the twenty-four and the twenty-sixmembered ring diketones the abstraction of the 7-hydrogen atoms with very large contactdistances (> 3.12 A) can tentatively be ruled out. Successful intramolecular 7-hydrogenabstractions in the solid state have experimentally been shown to be feasible over contactdistances of up to 3.1 A.79 Therefore, the abstraction of the 7-hydrogen atoms withdistances close to 3 A may be possible in diketones; however, the reported abstractions ofthe 7-hydrogen atoms with contact distances close to 3 A have better angular parametervalues of w and A for abstraction, which are also important in determining hydrogenabstractability. Such abstractions in the diametric diketones cannot be provedexperimentally from the photochemical results, since abstraction of all four accessible70hydrogen atoms would eventually lead to the same cis-cyclobutanol photoproduct.However, as discussed below, the photochemical results from the non-diametric sixteenmembered ring diketone solve this ambiguity.Although there are two pairs of non-equivalent 7-hydrogen atoms present indiketone 15, owing to the C2 symmetry of the solid state conformation, only the non-equivalent hydrogen atoms H6 and H10 need to be considered. The 7-hydrogen atomH10 (d = 2.72 A, co = 53.3°, A = 81.4°, 9 = 115.7°) is more stereoelectronically favoredfor abstraction by the carbonyl oxygen than H6 (d = 2.99 A, co ,= 59.0°, A = 65.5°, 0 =116.6°). Interestingly, the angular parameters of H6 are quite similar to those of the 7-hydrogen atoms with longer contact distances (3 A) found in all other diketones. Theabstraction of H6 and H10 could afford the cis-cyclobutanol derivative regioisomers 15C2and 15C1 respectively, but the solid state photolysis leads almost exclusively to 15C1 viathe abstraction of the stereoelectronically favoured hydrogen atom H10. A mere 2%formation of 15C2 is an excellent experimental evidence for a poor abstraction of the 7-hydrogen atoms having contact distances close to 3 A in diketones.3.2.4 Singlet and Triplet Reactions of Diketones.In solution, except for the smaller membered rings, the stereoselectivitycharacteristic of the solid state is largely lost, but a slight preference for trans over cis-cyclobutanol derivatives is observed. As is well established for the type II reactions ofaliphatic carbonyl compounds, 59,229 photochemical reactions of diketones were found tooccur via both the singlet and triplet n,n* excited states. Type II reactions were in factone of the first known photochemical processes involving both electronic states. 149,150In an attempt to investigate the multiplicity-dependent photochemistry ofdiketones, quenching studies of diketone 9 were performed using 2,3-dimethy1-1,3-butadiene as a quencher. As described in the Experimental Section, irradiation of 10-2 M71diketone 9 in hexane was carried out at various quencher concentrations. The resultsindicate that all three photoproducts, cis-cyclobutanol (9c), trans-cyclobutanol (9t) andthe cleavage product ene-dione (9e), are formed from both the singlet and triplet excitedstates. The product ratios at 0% conversions were calculated, as described earlier in thissection, for different quencher concentrations, and were plotted as a function of quencherconcentration (Figure 40). The singlet product ratios were obtained from the plateau ofthe graphs and normalized to 100% (Table VI).Three notable differences can be seen in the singlet state product distributioncompared to that of the direct photolysis (Table VI):(1) The predominant formation of the trans-cyclobutanol derivative is reversed.(2) The value for the cis/trans ratio is increased.(3) The value for the cleavage/cyclization ratio is increased.(a)450500.00^0.20^0.40^0.60^0.80^11)0^1.20^1.40^1.80^2.00quencher concentration (M)72(b) 0.00^0.20^0.40^0.60^0.80^1.00^1.20^1.40^1.60^1.80^2.00quencher concentration (M)Figure 40: a) Ene-dione/trans versus quencher concentration plot. b) Ene-dione/cisversus quencher concentration plot.Table VI: Type II product ratios of diketone 9, from direct photolysis and photolysiswith the quencher.medium excited state cis (%) trans (%) cleavage (%) cis/transhexane triplet + singlet 22 35 43 0.63hexane-quencher singlet 21 16 63 1.31Reactions of both the singlet and triplet excited states are generally known to bequalitatively similar, but quantitatively different. The observed product distributions seemto reflect the quantitative differences in the photochemistry of singlet and triplet excitedstates. It has been well recognized that triplet type II reactions occur completely viabiradical intermediates, while singlet reactions occur through a biradicalintermediate,76,151,152 as well as via a concerted mechanism (Figure 41).59,137 Theevidence for concerted processes from the singlet excited states comes from thehydrogenabstractionconcerted 0-■ singlet productsBR14hydrogenabstractiontriplet productsBR373stereospecific formation of the type II products 153,154 and from the radiationless decayback to the starting ketone (S0) with preserved stereochemistry at the 7-carbon atom.155singlet productsSo^Si^ISO^04TiFigure 41: Singlet and triplet pathways of type II reactions in diketones.In aliphatic carbonyl compounds, owing to much slower intersystem crossing (kst= —1.5x108 sec-1)230 from singlet to triplet excited states compared to those of aromaticcarbonyl compounds, longer singlet excited state lifetimes are generally observed. Theestimated lifetime of an excited singlet state of an aliphatic carbonyl compound has beenreported to be approximately 10 ns.156 In such time scale bond rotations may not beallowed in the singlet excited molecules. Even though the carbonyl carbons very likelypyramidalize upon excitation, the carbon skeleton of the ground state molecularconformations will be preserved; thus, the stereochemistry of the product formed byconcerted cyclization may reflect the conformations of the ground state molecule. Asdepicted in Figure 42, the concerted singlet reaction of the solid state conformation of thesixteen membered ring diametric diketone 9A would stereospecifically afford thephotoproduct cis-cyclobutanol derivative (9c).cis-cyclobutanolphotoproductsinglet excited state (Si)diketone74Figure 42: Diagrammatic representation of the formation of cis-cyclobutanol derivative9c by the concerted cyclization of the solid state conformation of diketone 9.The possible low energy conformations of diketone 9 generated by MM2calculations indicate that the solid state conformation has the least energy. Nineteen otherlow energy conformations were also found within a 10 Umol-1 energy window above thesolid state conformation. The first ten low energy conformations are given in Figure 43.Analysis of these conformations reveals that the majority of the conformations have abuilt-in preference for cis-cyclobutanol formation (0--H contacts in conformations withbuilt in preference for trans-cyclobutanol formation are indicated by dotted lines).Therefore, the relatively large amount of cis-cyclobutanol formation from the singlet statereaction may be partly due to concerted cyclization.On the other hand, the observed results may also be an outcome of the quantitativedifferences in the product distribution of the singlet and triplet biradical intermediates, dueto their different lifetimes. It is well known that C—C bond rotation rates157 are generallymuch faster than the relatively longer triplet lifetimes of the 1,4-biradicals. Therefore, indiketones, as generally observed in other aliphatic ketones, the triplet biradicalintermediate would be likely to reach a conformational equilibration.158,159 However, thesinglet biradicals are relatively quite short lived, and hence any significant conformationalchanges are thought to be generally impossible before they collapse to products.75Therefore, the concerted mechanism and the short singlet biradical intermediatelifetimes would account for the preference for cis-cyclobutanol derivative over transrelative to the direct photolysis, which occurs through both singlet and triplet excitedstates. The larger values for the cleavage/cyclization ratio observed in the singletreactions compared to the direct photolysis of the diketone 9 are quite surprising, butsimilar results have been reported for acyclic aliphatic ketones as well. 155,160 However, insmaller membered cyclic ketones (cyclododecanone), singlet state reactions have beenreported as giving high degrees of cyclization products.131,134conformation^relative energy.9A^0.0 kJ morl98^2.0 kJ moilconformation^relative energy.769C 3.6 kJ moll9D^4.9 kJ moll9E^5.3 kJ mollconformation^relative energy.779F 6.3 kJ morl9G 6.5 kJ morl9J 7.6 kJ mollconformation^relative energy.789H^6.7 kJ mo1-191 6.8 kJ morlFigure 43: Possible low energy conformations of diketone 9 generated by MM2.The diketones with rings larger than twelve membered may be quite flexible andtherefore may be able to explore various conformations in the isotropic medium.Therefore, the molecular motions necessary to form the type II products may be allowedwithout much strain in the ring. During the triplet reactions, since many bond rotationsare allowed during the relatively longer biradical lifetime, the triplet biradicals can easily79attain conformational equilibrium and may partition to produce larger amounts of trans-cyclobutanol than cis-cyclobutanol. The formation of larger amounts of the trans-cyclobutanol derivative may be attributable to the greater strain energy intrinsic to the cis-isomer. 162 The triplet sensitization reactions of diketones have been attempted for thesixteen membered ring diketone using acetone as the sensitiser; however, a completephotosensitisation could not be achieved. Although reports indicate successful acetonesensitisation of the photoreactions of saturated aliphatic ketones, the triplet energy (ET =80-81 kcal 1)163 may not be sufficiently high to sensitize diketone 9.The quantum efficiencies of the triplet type II reactions of medium size cyclicketones131 as well as those of acyclic ketones are generally reported to be much higherthan those of the singlet processes. The product distributions from the triplet biradica1swill therefore dominate in the direct photolysis. In fact, in this group of diketones, withthe exception of the twelve membered ring diketone 7, preference for trans-cyclobutanolderivatives over cis is observed during direct photolysis.The direct photolysis quantum yields of the photoproducts of the diketones 9, 10and 12 were measured using standard procedures164 (see Experimental Section) inbenzene at A, = 313 nm. The observed values given in Table VII are the average of threemeasurements. Due to the partial overlapping of the GLC peaks corresponding to the cis-cyclobutanols of diketones 10 and 12, only approximate quantum yields could beestimated from the areas of GLC peaks relative to the other products.The quantum yields for cyclobutanol formation from diketone 9 are quitecomparable to the reported values for the cyclobutanol formation from acyclic alkanonesin non-polar solvents (e.g., cyclobutanol formation from 2-hexanone, ocy = 0.075).160For the elimination process, significantly higher values are generally reported for theacyclic ketones (e.g., acetone formation from 2-hexanone, 4c1 = 0.252);160 however,quite similar values were reported for the elimination processes of cyclododecanone incyclohexane (0c1 = 0.043).131 The overall quantum yield for type II product formation80observed in diketone 9 is significantly lower than that for aliphatic acylic160,165 and cyclic(cyclododecanone)131 ketones reported in non-polar solvents.Table VII: Quantum efficiencies of type II photoproduct formation from diketones 9, 10and 12.diketone (ring size) cis trans cleavage9 (16) 0.019 (± 0.004) 0.031 (± 0.005) 0.054 (± 0.009)10 (18) 0.015 0.038 (± 0.008) 0.045 (± 0.007)12 (22) 0.009 0.032 (± 0.006) 0.037 (± 0.006)The almost exclusive formation of cis-cyclobutanol derivative 7c from the solidstate photolysis of the twelve membered ring diketone 7 can be explained from the X-raycrystal structure by using the same rationale as used for the other diketones. However,the stereoselective formation of the cis-cyclobutanol derivative in solution is interesting toconsider. A similar stereoselective formation of a cis-cyclobutanol derivative (cis:trans =—6:1) has been reported in the solution state photolysis of cyclododecanone.130,131,134As observed in cyclic diketones, photoreactions of cyclododecanone occur via both thesinglet and triplet excited states. The singlet state reaction gives cis-cyclobutanol almostexclusively (cis/trans = 25), but the efficiency of the singlet reaction has been reported tobe quite small compared to that of the triplet reaction (Ot = 0.53 / 0.03).131Experimental results indicate that cyclododecane and its derivatives105,161generally exist in a single square [3333] conformation in isotropic media even at roomtemperature. In solution, a square conformation [3333], with the carbonyl at the non-corner position, has been confirmed as the single and only conformation forcyclododecanone (monoketone), by Anet and co workers105 from their 13C nmr studies at81140 K and by 1Cristiansen and Ledaa1161 from their 1H nmr results at room temperature.The almost exclusive formation of the cis-cyclobutanol from the singlet reaction of themonoketone could be explained by the concerted mechanism or a mechanism proceedingthrough the short lived singlet biradical intermediate, as suggested by Matsui et al.134MM2 calculations of diketone 7 reveal six non-diamond lattice conformations (7A,7B, 7C, 7D, 7E and 7F) within a 10 kJ mold energy window, as depicted in Figure 44.The solid state conformation 7A was found to be similar to the global minimum. Usingthe calculated strain energies of these conformations, the Boltzmann distribution at 20°Cwas calculated. The ratio of the conformers 7A:7B:7C:7D:7E:7F is 84:8:3:2:<2:<2.Therefore, as predicted by Da1003 from his qualitative analysis, the solid stateconformation should be predominant in isotropic media. As observed in the solid stateconformation, the abstraction of any of the accessible y-hydrogen atoms (with theexception of H5 in conformation 7F) by the carbonyl oxygen atoms would lead to a pre-cis biradical intermediate.The results suggest that, in diketone 7, the biradical intermediate may havedifficulties attaining a pre-trans conformations. The majority of the triplet biradicalconformers of diketone 7 in the equilibrium distribution may have pre-cis arrangements asobserved in the low energy conformations generated by MM2. A careful inspection of themolecular models of the biradical intermediates of the twelve membered ring diketonereveals that the biradical closure through "path b" or "path c" (Figure 39b) to form trans-cyclobutanol involves severe transannular short contacts. Such conformational changesnecessary for the formation of the trans-cyclobutanol may be energetically unfavorable indiketone 7.However, the small amounts of trans-cyclobutanol observed in thecyclodecanone131 suggests that this factor is less important in the case of the monoketone.The results indicate a possibility of limited amounts of interconversions between pre-cisand pre-trans biradical intermediates during the triplet biradical lifetime. Burchill et a113182demonstrated the formation of small amount of trans-cyclobutanol from cyclododecanoneby ring rotations, but the molecular model analysis does not seem to correlate with thisexplanation. An ideal orbital overlap for cleavage may be equally difficult in such a smallring; therefore, the formation of appreciable amounts of the ene-dione cleavage productfrom the diketone 7 is rather surprising, and will be discussed later in this chapter.conformation^relative energy.7A^0.0 kJ moll7B^5.7 kJ mollconformation^relative energy.837C^7.86 kJ mai7D^9.24 kJ mai7E^9.66 kJ morl84conformation^relative energy.7F^9.67 kJ morlFigure 44: Possible low energy conformation of diketone 7 generated by MM2.3.3. Diketones that Give trans-Cyclobutanol as the Major Product in theSolid State.3.3.1. Solid State conformation and Photochemistry.A stereoselective formation of trans-cyclobutanol derivatives was observed as themajor process (Table IV) in the solid state reactions of the eighteen membered ringdiketone 10, the twenty two membered ring diketone 12 and the twenty six membered ringdiketone (needle crystal modification) 14N. The solid state conformations are depicted inFigure 45.The solid state conformation of the eighteen membered ring diketone 10 has beenreported by Allinger et all° to have the carbon atoms arranged in a diamond latticeconformation with C2h molecular symmetry (Figure 45a), but not a rectangular one whichmight have been expected for a large ring. However, the diamond lattice rectangularconformation [3636] generated by molecular mechanics force fields166 was found to have854.8 k.lmol-1 higher energy than the solid state conformation. In the case of the twenty sixmembered ring needle crystal modification (a dimorph of the plate crystal modification),the conformation is "zig zag" shaped, where the indentations in the methylene chain alongone side of the long molecular axis are matched by extrusions on the other.As predicted by Dale98a, the twenty two membered ring, which belongs to the(CH2)4n+2 series, could adopt a diamond lattice rectangular conformation [3838];however, nature seems to crystallize it in a more complex conformation as shown inFigure 45b. Interestingly, in this group of diketones the carbonyls are anti to each other,and not surprisingly an even number of methylene carbons is present between the twocarbonyl groups. The geometrical parameters of the y-hydrogen atoms are summarized inTable VIII.(a)(b) (c)86Figure 45: Solid state conformations of (a) eighteen, (b) twenty two, (c) twenty six(needles) membered ring diketones (the y-hydrogen atoms with short 0-...Hcontacts (d < 2.82 A) are indicated by dotted lines).3.3.2. Hydrogen Abstraction Geometry and Biradical Geometry.As observed in the previous section, all y-hydrogen atoms having short 0....H(d < 2.82 A) contacts make boat-like abstraction geometries, whereas the other 'y-hydrogen atomst s make chair-like abstraction geometries with contact distances larger than3 A. In the highly symmetrical conformation of the eighteen membered ring diketone 10,87all four closest y-hydrogen atoms, which are equivalent by symmetry, make anintamolecular six-membered cyclic 0....H contact of 2.78 A with the carbonyl oxygenatoms.As indicated in Table VIII, the twenty six membered ring diketone (needles) 14Nhas a pair of y-hydrogens (H6 and H29) that have short 0....H contacts close to the idealvalues (2.73 A), whereas in the twenty two membered ring diketone one y-hydrogen atomhas an 0...H contact of 2.71 A, and the other one of 2.82 A. A 8-hydrogen atom (H7) ofthe twenty two membered ring diketone 12 makes a seven membered cyclic 0....H contactof 2.89 A with favorable angular geometry (Table VIII) for abstraction, but acyclopentanol derivative was not detected during the photolysis. The rate of 8-hydrogenatom abstraction is generally known to be much slower than that of y-hydrogen atomabstraction for equivalent C-H bonds. 64 This difference has been suggested to be due tothe greater entropy loss and torsional strain during 1,6-hydrogen transfer, compared to1,5.60 The other y-hydrogen atoms in both the twenty two membered ring (H26) andtwenty six membered (needle) ring (H20 and H43) diketones have 0....H contacts greaterthan 3.10 A, and make chair-like abstraction geometries.Table.VIII: The y-hydrogen geometrical parameters of diketones that give trans-cyclobutanol derivatives as the major solid state photoproducts.DIKETONE(RING SIZP)y-hydrogen ^abstractedabstractingoxygend (A) co (°) A (°) 0 (°) abstractiongeometry18 H5 01 2.78 54.1 78.3 112.7 BOAT22 H7 (8) 01 2.89 63.5 63.0 146.6 -H16 02 2.82 52.1 80.5 111.4 BOATH26 02 3.10 56.6 58.6 114.3 CHAIRH35 01 2.71 44.2 87.7 113.6 BOAT26N H6 (H29) 01(02) 2.73 48.6 84.6 114.9 BOATH20 (H43) 02 (01) 3.26 57.2 57.5 100.0 CHAIRH(1)..,, C5H CH2C3C2^ClHH^Cn-1 CH2/(2)(2)\ Cn-1 HH CH2^,I C5C4 I ---CH2H^ci^,^IC288The two types of abstraction geometries and their Newman projections down theC2-C3 bonds are depicted in Figure 46.Figure 46: a) (1) Newman projection down the C2-C3 carbon-carbon bonds (boat-likeabstraction geometry).(2) Pictorial representation of boat-like hydrogen abstraction geometry.b) (1) Newman projection down the C2-C3 carbon-carbon bonds (chair-likeabstraction geometry).(2) Pictorial representation of chair-like hydrogen abstraction geometry.89From the diagram it is apparent that the abstraction of any y-hydrogen atom (withthe exception of H20 and H43 from the twenty six membered ring diketone) that has ashort 0- -.H contact with the carbonyl oxygen leaves the unabstracted y-hydrogen atomand the oxygen atom in an anti relationship in the biradical intermediate. The biradicalintermediate from the eighteen membered ring diketone 10 and its biradical reactioncenter, shown in Figure 47, are typical for this group of diketones.3.3.3. Structure Reactivity Correlation.In the solid state, as depicted in Figure 47, the least motion closure of the biradicalintermediate through "path a", with retention of the orientation of the hydroxy group andthe unabstracted y-hydrogen atom at the Cl and C4 carbon atoms, would lead to thetrans-cyclobutanol derivative as the major photoproduct. This is precisely theexperimentally observed result as indicated in Table IV.In the solid state conformation of the twenty six membered ring diketone (needle)14N, in addition to the two closest 'y-hydrogen atoms H6 and H29 (d = 2.73 A, co = 49°,A = 85°, 9 = 115°), the other two y-hydrogen atoms H20 and H43 (d = 3.26 A, co = 57°,A = 58°, 0 = 100°) make a chair-like abstraction geometry which can be considered foranalysis. The abstraction of H6 (H29) is obviously preferred on the basis of its abstractionparameters and would lead to a pre-trans biradical intermediate. On the other hand, it isapparent from the solid state conformation of diketone 14N that the abstraction of H20(H43) should lead to a pre-cis biradical intermediate. However, upon irradiation, theneedle like crystals of the twenty six membered ring afforded 91% trans-cyclobutanol and9% cis-cyclobutanol derivatives. It is interesting to point out that, as described earlier inthis chapter, the irradiation of its dimorphic plate-like crystals is highly stereoselective forcis-cyclobutanol. Such widely divergent photochemical stereoselectivity observed fromHS ak^H2•C IHE90these conformational polymorphs is one of the rare examples found in theliterature.57d,167,168,169Figure 47: a) Biradical intermediate from diketone 10. b) Biradical intermediate reactioncenter.The solid state photochemical results of the dilcetones analyzed so far can beexplained in terms of the solid state molecular conformations obtained by X-ray. Thisindicates that the diketones react in a topochemically, conformationally specific manner inthe crystal. However, the formation of 9% cis-cyclobutanol from the twenty sixmembered diketone 14N is explicable as arising from either abstraction of H20 (H43) orthe loss of control of the biradical closure following the abstraction of H6 possibly due tothe presence of defect sites. Since low temperature reactions afforded similar results,1416^ 1410CS^C71415^02^HS14130 01411.H17^147C11^•. •^CSH121^.• 1412CWCs•• . C91crystal melting during photolysis can be ruled out. A similar argument would correctlyaccount for the formation of the minor products observed in the solid state reaction ofother diketones analyzed so far. This suggests that the reaction cavities in these diketonecrystal lattices allow limited amounts of motion to the excited state molecules or to thebiradical intermediates.In solution, the product ratios are comparable to the solution results observed inthe previous section. A similar rationale can therefore be offered to explain the loss ofstereoselectivity and the preference for the formation of the trans-cyclobutanol over cis.3.4. Diketones in which the Stereoselectivity is Significantly Lowered inthe Solid State.The fourteen membered ring diketone crystallizes in a rectangular diamond latticeconformation [3434] (Figure 48).Figure 48: Solid state conformation of the fourteen membered ring diketone 8.92The two carbonyls in the molecule are placed in the middle of the longer segment(P-to the comer atom), rather than on the short segment as generally observed in the otherrectangular conformations of diketones. In the solid state reactions of the diketonesdiscussed in this thesis, it is interesting to note that the general alternating trend observedin the stereoselectivity of cyclobutanol formation with respect to ring sizes is not followedby the fourteen membered 8 and twenty six membered (plates) 14P ring compounds. Ifthe trend were followed, one would expect a stereoselective formation of trans-cyclobutanol as the major solid state product from both fourteen and twenty-sixmembered diketones.As discussed earlier in this chapter, the plate dimorph 14P gives cis-cyclobutanolexclusively, whereas in the fourteen membered diketone 8, the corresponding cis-cyclobutanol was obtained as the major product. However, the needle dimorph of thetwenty six membered ring diketone 14N obeyed the trend observed for type IIstereoselectivity. Interestingly, these two examples have rectangular diamond lattice solidstate conformations [3x3x], whereas all other diketone rectangular conformations have anon-diamond lattice arrangement.An inspection of the fourteen membered solid state conformation reveals that thereare four equivalent 'y-hydrogen atoms (H6, H7, H17, H19) (d = 2.71 A, 0) = 52.5°,A = 83.0°, 0 = 116°) located favorably for abstraction through a six-membered boat-likeabstraction geometry. The Newman projection through the C2-C3 bond and theabstraction geometry common to all four hydrogen atoms is depicted in Figure 39b. Uponirradiation, the abstraction of any of these four hydrogen atoms would lead to a pre-cisbiradical intermediate. Therefore, in the solid state, the least motion closure with retentionof the orientation of the unabstracted y-hydrogen and the hydroxy group at C4 and Clrespectively should have led to the formation of cis-cyclobutanol. Surprisingly, thestereoselectivity is significantly lowered compared to the selectivity observed in the solidstate reactions of the other diketones, although, as indicated in Table IV, preference for93cis-cyclobutanol formation over trans-cyclobutanol (cis:trans=2:1) is maintained. Thepredominant formation of the cis-cyclobutanol derivative in isotropic media is similar tothe solution results with the twelve membered ring diketone 7 and the monoketones130described earlier in this chapter.The formation of trans-cyclobutanol in the solid state reaction from diketone 8 israther surprising, as it cannot be related to the solid state conformation, and clearlyindicates the partial loss of topochemical control. Such abnormal non-topochemicalbehaviour, which cannot be explained by structure-reactivity correlations, may be theresult of one or more of the following situations:1)Crystal melting and concomitant loss of topochemical control.2) A fraction of the excited state molecules or the 1,4-biradical intermediates mayreside in defect sites.3) There might be a difficulty in the formation of the twelve membered ring (largerring in the cyclobutanol derivative) from the fourteen membered ring (dilcetone).Since the melting point of this diketone is fairly high (148-149°C), the highestamong all diketones investigated, the loss of stereoselectivity is probably not related tocrystal melting during photolysis. Furthermore, lowering the photolysis temperature hadno effect on the product distributions. Therefore, the loss of topochemical control due tocrystal melting can be ruled out.Any conformational rearrangements in the constrained solid state lattice mediumwould involve high transition state potential energies. However, excited state moleculesor biradical intermediates residing at defect sites could undergo such transformations. Thedefect sites in crystal lattices, unlike regular lattice sites, are generally known to providequite flexible reaction cavities, with enough free volume for the molecules to undergo suchconformational changes. In the case of the fourteen membered ring diketone 8, during thesolid state photolysis the excited molecules or the biradical intermediate molecules at the94regular lattice sites may topochemically afford cis-cyclobutanol as the majorphotoproduct, whereas the molecules residing at defect sites may undergo conformationalisomerization or may even reach conformational equilibrium (if the biradical lifetimepermits), and consequently afford both cis and trans-cyclobutanol derivatives. A largerthan normal value of the residual index R factor (0.073) of the crystal structure ofdiketone 8 may be an indication of the presence of such defect sites in the crystal lattice.On the other hand, a greater degree of difficulty associated with biradicalcyclization to form cyclobutanol photoproducts possessing twelve membered rings mayalso be partially responsible for the loss of topochemical control. Such difficulty in thecyclization process may increase the lifetime of the biradical intermediate and as a resultallow time for the molecules to equilibrate conformationally. Cyclization processes thatform medium size ring compounds are generally known to be difficult. Evidence tosupport this can be seen from the rate constants reported for the ring closure reaction toform cyclic lactones.170 A significant drop in the rate constant for twelve membered ringformation compared to that of the thirteen membered ring analogue has been reported.Although the entropy factor favours formation of the twelve membered compared to thelarger membered rings, the unfavorable enthalpy factor in the medium size ring formation,presumably due to transannular interactions, increases the activation energy for thecyclization process. A molecular model analysis also indicates severe transannularcontacts during the cyclization process of the diketone 8 biradical intermediate.A similar situation may also exist during the photolysis of the twelve memberedring diketone 7 (the single square conformation has a built in preference for cis-cyclobutanol), but the ring size may not be large enough to allow conformational changefrom the pre-cis conformer into pre-trans, even during the lengthened biradical lifetime;thus, only cis-cyclobutanol derivatives were observed.At this point, investigation of the low energy conformations of fourteen memberedring diketone 8 may provide valuable information. The molecular mechanics calculations95of diketone 8 generated five low energy conformations (8A, 8B, 8C, 8D and 8E) within a5 kJmo1-1 energy window. The conformations are depicted in Figure 49. The solid statediamond lattice conformation 8A was found to be the global minimum. From hisqualitative analysis 1°3 Dale concluded that the solid state conformation is the predominantconformation in solution as well. However, our calculation shows the conformation 8Bhas only 0.3 klmo1-1 higher energy than the global minimum.conformation^relative energy8A^0.0 kJ morl8B^0.3 kJ malconformation^relative energy968C^2.0 kJ moll8D^2.8 kJ morl8E^4.5 kJ morlFigure 49: Five low energy conformations of diketone 8 generated by MM2.H2 H2I-21 CI H3HI3 HII8A 8BH2^ 01 H4C2C13H2 ,'^ HI0241^It 10H20C11-120°H14CIOit 4611111.^'MPHISHSHSH7^HeCSHI2 C602H10H9C9^C7H19H1697The Boltzmann distribution at 20°C (8A:8B:8C:8D:8E = 35:32:15:12:6) indicatesalmost equal amounts of 8A and 8B at equilibrium. Conformation 8A can isomerize into8B by —120° bond rotations around C10-C11 and C12-C13 (Figure 50). In conformation8B the abstraction of the y-hydrogen atom H19 (d = 2.81 A) by the carbonyl oxygen atom01 will afford a pre-trans biradical intermediate. A similar pre-trans biradicalintermediate is also possible from the abstraction of the y-hydrogen atoms H8 or H19 inconformation 8D. However, the abstraction of the rest of the y-hydrogens in these lowenergy conformations would afford pre-cis biradicals. Therefore, conformationalisomerization of the biradical intermediates as a result of both the flexible reaction cavitiesat the defect sites and/or the longer biradical lifetimes may contribute to the significantloss of stereoselectivity in the solid state.Figure 50: Conformational isomerization from 8A to 8B.98In solution photolyses, the contribution of low energy conformations and theisomerization of the biradical intermediates would correctly account for the loss ofstereochemistry. However, the preference for the more strained cis-cyclobutanolformation over its stereoisomer is also observed in other small membered monoketonesand in the twelve membered ring diketone. The observed solution results indicate thateither the equilibrium conformations of the biradical intermediates possess largely the pre-cis conformations (MM2 calculations further support this) rather than pre-trans, or thepre-trans biradical intermediates may have more difficulty achieving the best overlap forclosure than the pre-cis, due mainly to the size of the ring. The absence of trans-cyclobutanol formation from the twelve membered ring diketone clearly suggests that thepre-trans biradicals are impossible due to ring size.The seventeen membered ring diketone does not show any stereoselectivity eitherin solution or in solid states. The X-ray structure of these compounds could not beobtained due to their poor crystal quality, as is often the case with the odd memberedcyclic compounds. The loss of stereoselectivity may be due to:1) A single solid state conformation that leads to both pre-cis and pre-transbiradical intermediates.2) The lattice may contain many defect sites as indicated by the poor crystalquality.The solution-like product distribution in the solid state photolysis suggests that themajority of the molecules are residing at defect sites. The reaction cavities at these defectsites may be quite flexible, with large free volumes to allow conformational isomerizationto yield almost solution-like product distribution. Although the melting point of thediketone is quite low (68-69°), lowering the photolysis temperature had no effect on theproduct ratios.993.5. Chemoselectivity in the Solution and Solid State Photoreactions ofDiketones.The cyclization to cleavage product ratios from the type II reaction of thediketones at 20°C are compiled in Table IX. From the table it is apparent that, with theexception of the fourteen and seventeen membered rings, all diketones undergo morecyclization in the solid state reaction than in the corresponding solution reaction. In thefourteen and the seventeen membered ring diketones, however, cyclization/cleavage ratiosare almost the same in both media. There are several reports of type II reactions wherecyclization/cleavage ratios in the solid state and in solution are practically identical asobserved in the fourteen and seventeen membered ring diketones.57f,171 The preferencefor cyclization over cleavage observed in the irradiation of diketones in cyclohexane seemsto vary with ring size. In the case of both the twelve and fourteen membered ringdiketones, a high degree of cyclization is observed in both media, and thecyclization/cleavage ratios are comparable, as opposed to the larger membered rings,where the amount of cyclization and cleavage are almost equal in the isotropic media. Asimilar trend in the chemoselectivity has been reported for irradiation of monoketones incyclohexane (Table II), as mentioned earlier in this chapter.130The preference for cyclization products in the solid state photochemistry ofdiketones can be related to the 1,4-biradical geometry. It is assumed that the hydrogenabstraction occurs in the crystalline phase with minimal conformational changes, toproduce biradicals with the same basic conformation as their ketonic precursor. Theconformation of the biradical intermediate reaction sites can be defined by three torsionalangles, 01, 02 and 0.01 - Angle of the p-orbital on Cl with respect to the C2-C3 bond.02 - Angle of the p-orbital on C4 with respect to the C2-C3 bond.0- Dihedral angle of Cl-C2-C3-C4.100The torsional angles 01 and 02 (Figure 51), are calculated from the X-ray crystalstructure data based on two assumptions:1) The hybridization of the ring carbon C4 bearing the unabstracted y-hydrogenatom changes from sp3 to sp2.2) The p-orbitals at Cl and C4 lie perpendicular to the planes delmed by01-C1-C2 and C3-C4-05, respectively.Table IX: cyclization/cleavage ratios of diketones both in solution and solid state.DIKETONE(ring size)CYCLIZATION (%) CLEAVAGE (%)SOLID STATE HEXANE SOLID STATE HEXANE12 99 84 <01 1614 87 90 13 1016 99 57 01 4318 87 59 13 4120 94 33 06 6722 95 44 05 5624 99 42 01 5826 (P and N) 100 47 00 5316* 100 61 00 3917 49 53 51 47C2 8 C3 01^02C l^ C4Cn-1 C50 1Figure 51: A diagrammatic representation of the biradical intermediate reaction centershowing 01, 02 and 0 angles.101The 01 and 02 values and the torsional angles around the central sigma bond aregiven in Table X.Table X: Biradical parameters of diketones.diketone(ring size)7-hydrogen carbonyl oxygen 01 (0) 02 (0) C2 -C3 dihedralangle (°)10 H3 (H12) 02 (01) 67.5 -30.3 62.612 H6 (H16) 01 12.2 85.0 -60.3H6 (H16) 02 55.9 21.2 -64.614 H6 01 -65.6 -25.2 64.216 H6 01 -67.2 -24.4 65.6H10 02 -19.3 -83.5 70.7H20 02 -68.1 -24.5 68.5H24 01 -19.3 -86.0 60.518 H5 01 -69.1 -89.5 74.220 H5 01 71.4 24.4 -67.6H13 02 22.6 87.5 -59.2H23 02 69.4 24.9 -65.5H31 01 22.1 84.9 -58.422 H16 02 -68.7 85.6 67.8H26 02 -29.2 -82.3 59.8H35 01 80.6 -87.0 -69.424 H5 01 -27.1 -83.2 61.2H17 02 -73.8 -25.4 68.2H27 02 -30.8 -82.2 59.9H39 01 -71.6 -25.7 64.926N H6 (H29) 01(02) 73.3 -86.4 -69.01143 (H20) 01(02) -32.0 -81.2 58.126P 115 (H30) 01(02) -37.8 -82.6 -59.5H43 (H20) 01(02) 70.6 24.2 -67.416* H6 01 20.5 84.6 -64.0HIO 01 66.4 25.8 -63.6102The sign and the magnitude of the angles ei and 02 depend on whether the top orbottom lobe is used for measurement. The lobe which makes the smallest torsional anglewith the C2-C3 bond was chosen in each case. From Table X, it is apparent that allbiradical intermediate C1-C2-C3-C4 conformations are gauche rather than cisoid or anti,with dihedral angles around the central sigma bond on the order of 65°. As shown inFigures 39b and 47b, the singly occupied p-orbitals at Cl and C4 in the biradicalintermediate are in close proximity to one another, but are out of alignment with thecentral sigma bond C2-C3. In each case at least one torsional angle, either 01 or 02, isclose to 60°.As stated in the Introduction, due to orbital overlap considerations, the gauche orcisoid arrangements of the 1,4-biradical intermediates can undergo both cyclization andcleavage, while the anti arrangement undergoes cleavage exclusively. Furthermore, thereis general agreement that the cleavage of a 1,4-biradical requires a significant overlapbetween the central sigma bond being broken and the singly occupied p-orbitals.172Evidence for the above statement emerges from Hoffman's calculations, in which anextensive overlap between the p-orbitals and the central sigma bond of a 1,4-biradicalintermediate optimizes the mixing of it and a levels, which promotes cleavage.173Therefore, extensive atomic and molecular motions around the Cl-C2 and C3-C4bonds are required to align the p-orbitals on Cl and C4 with the C2-C3 bond to achievean ideal arrangement (i.e., the 01 and 02 need to approach 0°) for cleavage. Since asignificant overlap of the singly occupied orbitals through space is generally accepted asbeing necessary for a successful cyclization59,60,115,116, it is not surprising that thepreferred least motions in the solid state would lead to a predominant cyclization.In solution, as opposed to the solid state, alternative diketone conformations aswell as possible conformational isomerization of the 1,4-biradical intermediates can allowfor a better overlap of the singly occupied orbitals with the C2-C3 bond, and as a resultcan lead to increased values of the cleavage/cyclization ratio. However, the greater103degree of cleavage products from large rings, compared to that observed in twelve andfourteen membered rings, seems to indicate that in large rings, conformationalrearrangements of the biradical intermediates can more easily lead to the ideal orbitaloverlap for cleavage, including an anti conformation (which may be generally difficult incyclic compounds). Whereas in medium rings the Cl-C2 and C3-C4 bond rotations maybe limited from achieving significant overlap between the central sigma bond and singlyoccupied p-orbitals due to the ring size; thus, they stay in gauche or cisoid arrangements,which are rather intrinsic to cyclic ketones and yield larger amounts of cyclization.Analysis of the molecular models of medium rings indicates severe tansannular contactswhen the biradical intermediates are ideally placed for cleavage.For non-cyclic ketones, compared to the cyclic ketones, completely reversedcleavage/cyclization ratios are reported in the literature.115 The majority of the biradicalintermediates from non-cyclic ketones tend to stay in stable anti rather than cisoid orgauche conformations in isotropic media; not surprisingly, therefore, this leads to largeamounts of cleavage products. In the solid state and in the organized media, however,even larger cleavage/cyclization ratios have been reported for non-cyclic ketonescompared to those observed in isotropic media.162,174,175 From a fascinating type IIphotochemical investigation of a series of conformationally fixed cyclohexanones,Ian Fleming et al. showed a great influence of the orientation of the C2-C3 bond on thecleavage/cyclization ratio.176 Since a continuous orbital overlap with C2-C3 bond isconsidered necessary for the cleavage reaction, a higher degree of cyclization wasobserved from a molecule where the C2-C3 bond is held more or less in an orientationunfavorable for the C2-C3 bond cleavage. A similar analysis would clearly explain thelarger degree of cyclization observed in the twelve and the fourteen membered ringdiketones in the solution photolysis. In the gauche biradical conformation the C2-C3bond may have difficulty attaining a favorable orientation for cleavage due to the smallring size.104The small amounts of cleavage products in the twelve and fourteen membereddiketones in isotropic media can be explained by "pseudorotation" 105,177,178 of the rings,a process much like the out-of-plane methylene group "puckering" of the cyclopentaneenvelop conformation rotating around the ring.179 Similar ring motions have beenproposed for the high temperature solid phases of the cyclic compounds that undergosolid-solid phase transitions.98a Such rotations have been well investigated forcyclododecanone (Figure 52) in isotropic media. 105A ring rotation of the biradical intermediate of the diketone can place both singlyoccupied orbitals at corner positions from the non-corner positions, and thus the biradicalsare no longer gauche but anti, with both p-orbitals considerably overlapped with thecentral a-bond. The estimated rate constant105 for such conformational interchange incyclododecanone between conformations having the C=0 group at corner and non-cornerpositions at room temperature is 2x107 s-1, and this is of the order of the triplet biradicallifetimes.158,159 In isotropic media, such rotations of the biradical intermediates of thesmaller rings may account for the formation of cleavage products in appreciable amounts.A similar argument has been proposed by Burchill et al.131 for the formation of smallamounts of cleavage products from cyclododecanone. During the solid state reaction ofthe fourteen membered ring diketone 8, similar rotations of the biradical intermediates atdefect sites may partially account for the formation of 13% of cleavage product 8c.The large degree of cleavage product (-50%) observed in the solid state photolysisof the seventeen membered ring is comparable to its solution results. The solution-likecyclization/cleavage ratio is explicable using the same analogy used to explain the loss ofstereoselectivity observed in the solid state reaction. A similar explanation wouldcorrectly account for the loss of topochemical control in the photochemistry of the keto-alcohols. Crystals could not be grown for either keto-alcohol 29 or 30, but as observed inthe seventeen membered ring diketone, they exist in powder or amorphous form. Theobserved product ratios indicate that the reaction cavities are quite flexible and the freegauche105volume present in the cavities are large enough to allow solution-like conformationalchanges as observed in the seventeen membered ring diketone.antiFigure 52: Hypothetical conformational interchange (pseudorotation) of cyclododecanonebiradical intermediate from gauche to anti conformation.3.6. Photochemistry of the Ten Membered Ring Diketone.As described earlier in this chapter, the ten membered ring diketone 6 crystallizeswith the diamond lattice conformation 6C (Figure 53). The conformation has two y-hydrogen atoms, H3 and H12, having short 0.-H contacts (d = 2.74 A, co = 52.1°, A =91.7°, 0 = 113.3°) with favorable angular parameters for abstraction (the abstractiongeometries are boat-like); surprisingly, diketone 6 remains photostable both in solutionand in crystalline media. The two 8-hydrogen atoms, H8 and H15, also lie relatively closeto the carbonyl group, but the stereoelectronic disposition of these atoms with respect tothe carbonyl groups is quite different from that of the y-hydrogen atoms (d = 2.81 A, (0 =98.5°, A = 76.2°, 0 = 134.4'). The unfavorable value of the angular parameter co, which isclose to 90°, would make the 8-hydrogen abstraction unlikely.106Figure 53: ORTEP stereodiagram of diketone 6.Based on a low temperature X-ray crystal structure analysis, cyclodecanone101hasalso been reported to have a conformation similar to that of diketone 6C, with thecarbonyl next to the comer position (Figure 53). The same monoketone conformation hasalso been reported to have the lowest energy by MM2 calculations.136,180,181 Thismonoketone conformation has a 7-hydrogen lying close to the carbonyl groups, (d = 2.54A) with co angle = 560.136 However, cyclodecanone has long been known for the uniquee-hydrogen abstraction in cyclohexane (non polar) solvent.135 Sauers et al 136 recentlyreported the divergent photobehaviour of this cyclic ketone, which depends on the polarityof the isotropic medium (Figure 54). As opposed to the situation in cyclohexane,irradiation of cyclodecanone in t-BuOH, gave photoproducts formed via both the7-hydrogen abstraction (bicyclo[6.2.0]decan-1-ol) and the &hydrogen abstraction(9-decalo1). Lewis bases like tert-BuOH are known to solvate the hydroxy biradicalintermediate by forming a hydrogen bond with the hydroxy group of the biradicalintermediate and thereby suppressing the reverse hydrogen transfer back to the startingketone.59,115,116 Such an effect of the solvent molecules has been reported to beresponsible for the increased lifetime of the biralical intermediate in polar solvents.182107Si•hvS0y H-abstraction^■reverse c H-transfer reverse y H-transferOHe H-abstractioncleavage•- -cyclizationOHFigure 54: 7 and e-hydrogen abstraction pathways of cyclodecanone.During the photolysis of cyclodecanone in cyclohexane, both 7 and e-hydrogenabstractions are presumably feasible from lowest energy and other alternativeconformations, but an efficient reverse hydrogen transfer of the y-hydrogen atoms hasbeen suggested to explain the exclusive formation of 9-decalol (e-hydrogen abstraction).However, in polar solvents (tert-BuOH), the reverse hydrogen transfer is slowed down orprevented due to hydrogen bonding and therefore products from both 7 and &hydrogenabstractions have been observed in a ratio of 3:2.MM2 calculations of diketone 6 reveal three low energy conformations (6A, 6Band 6C) within a 20 kJ mold energy window (20 kJ mo1-1 above the global minimum), asillustrated in Figure 55. Interestingly, a conformation similar to the solid stateconformation 6C has the highest energy, and is totally different from the other twoconformations. Using the calculated strain energies of these three conformers, theBoltzmann distribution at 20°C was calculated. The ratio of the conformations 6A:6B:6Cis 97:2:1, so conformation 6A is the dominant conformation in solution.conformation^relative energy1086A^0.0 kJ mori6B^9.9 kJ morl6C^11.9 kJ meiFigure 55: Three possible low energy conformations of diketone 6 generated by MM2.109In the MM2-derived solid state conformation 6C, the angular parameters of the7-hydrogen (c) = 51.5°, A = 93•30, 0 = 113.00) and 5-hydrogen (co = 83.1°, A = 75.0°,0 = 136.3°) atoms are close to those found by X-ray, but the 0...H contact distances(cty = 2.54 A, ci6 = 2.63 A) are quite short compared to those of the solid state conformer.The highly symmetrical global minimum 6A has a diamond lattice conformation. Thereare four 5-hydrogen atoms with close 0...H contacts (d = 2.67 A) and angular parametersfavorable (co = 63.3°, A = 91.6°, 0 = 101.5°) for abstraction by the carbonyl oxygens. Thenon-symmetrical conformation 6B has a 7-hydrogen atom H13 with a close contactdistance of 2.52 A, and its other three 5-hydrogen atoms have contact distances of<2.79 A with the carbonyl oxygen. However, in both cyclohexane and t-BuOH, as wellas the solid state, diketone 6 was found to be photostable. As observed forcyclodecanone, the photostability may be due to an efficient reverse 7 or 5-hydrogenabstraction in the biradical intermediates (even in polar solvents) or an efficientdeactivation of the excited molecules by radiative or radiationless processes that areintrinsic to the molecule.3.7. The Best Geometrical Requirements for y-Hydrogen Abstraction inDiketones.The geometric disposition of the 7-hydrogens that have the closest 0...H contactsin each diketone are compiled in Table XI. Interestingly, in all diketones the transitionstate abstraction geometry is boat-like rather than a chair-like, which is considered to be apreferred strain-free transition state for 1,5-hydrogen abstraction.59,76,115 The nature ofthe six membered 1,5-hydrogen transfer abstraction geometry for type II reactions hasbeen investigated both theoretically and experimentally.110Table XI: Geometrical parameters corresponding to y-hydrogens having the closest 0...Hcontacts.ring size g-hydrogen d (A) co (°) A (°) 0 (°) product geometry12 H6 2.73 63.8 77.9 113.4 CIS BOAT14 H6 2.71 52.5 83.0 116.0 CIS BOAT16 H6 2.73 53.2 81.6 115.4 CIS BOAT16* H10 2.72 53.3 81.4 115.7 CIS BOAT18 H5 2.78 54.1 78.3 112.7 TRANS BOAT20 H23 2.69 52.1 84.2 114.8 CIS BOAT22 H35 2.71 44.2 87.7 113.6 TRANS BOAT24 H39 2.67 50.4 83.2 117.5 CIS BOAT26N H6 2.73 48.6 84.6 114.9 TRANS BOAT26P H20 2.76 52.0 82.1 113.1 CIS BOATaverage 2.72 52.4 82.4 114.7best 2.71 44.2 87.7 113.6Boer et al183 suggested a planar (01-C1-C2-C3-C4-7H) transition state for thetype II process and its radical cation state equivalent, the Mc Lafferty rearrangement.Lewis and Wagner have, however, disproved this planar structure for type II reactions,because the hydrogen abstraction rate constants in planar transition state geometries areexpected to be diminished significantly by sub stituents at the a and (3 positions. In aplanar transition state, any substituents at the a and 13 positions would cause unfavorableeclipsing interactions with the methylene hydrogens, resulting in higher activation energiesand consequently lower rate for 7-hydrogen abstraction. However, no such effect was111found and this led to the postulation of a strain free chair -like transition state byWagner.59,76,115In diketones, however, the y-hydrogen atoms which make chair-like abstractiongeometries have relatively unfavorable 5, co and A values for abstraction, compared to they-hydrogen atoms which make boat-like abstraction geometries. Of all the y-hydrogenatoms in Table XI, H35 in the twenty two membered ring diketone has the best values(d = 2.71A, co = 44.2°, A =87.7°, 9 = 113.6°) for abstraction. Interestingly, the parametervalues of all y-hydrogen atoms with closest 0.--H contact distances are quite close to theirmean values (d = 2.72A, co = 52.4°, A = 82.4°, 0 = 114.7').From the investigation of ene-diones and enone-alcohols (hydrogen abstraction byoxygen occurred over a range of 2.3-2.7A) conducted in our laboratory, 14 the idealdistance for hydrogen abstraction by an oxygen atom was suggested to be equal or lessthan the sum of the van der waals radii of the oxygen and hydrogen atoms (d 2.72A); inthese compounds, the values of co and A were also reported to be quite close to the idealvalues. In our present investigation, efficient y-hydrogen atom abstractions were found atdistances as high as d = 2.78A, co = 63.8°, A = 77.9°, 0 = 112.7°. However, these valuesmay not be the conclusive upper limit for diketones, since in each diketone more than oneaccessible y-hydrogen atom leads to the same photoproduct.Another investigation from our laboratory on a-cycloalkylacetophenones57frevealed that y-hydrogen atom abstractions are feasible with 0.--H contact distances up to3.1A, which is significantly higher than the ideal value, but the corresponding angularparameters were quite favorable for abstraction compared to those 'y-hydrogens with dvalues close to 3A of the diketones. Eleven out of fourteen compounds investigated inthis series underwent smooth reaction through boat-like abstraction geometries, asobserved in diketones. The torsional angles in Table XII describe the geometries of thebiradical intermediates corresponding to the closest y-hydrogen atoms in each diketone.112Table XII: The geometrical parameters of the biradical intermediates corresponding tothe y-hydrogen atoms having closest 0...H contact distances.ring size y-hydrogen 01 (°) 02 (°) 0 (°) product geometry12 H6 55.9 21.2 -60.3 CIS BOAT14 H6 -65.6 -25.2 64.2 CIS BOAT16 H6 -67.2 -24.4 65.6 CIS BOAT16* H10 66.4 25.8 -63.6 CIS BOAT18 H5 -69.1 -89.5 74.2 TRANS BOAT20 H23 69.4 24.9 -65.5 CIS BOAT22 H35 80.6 -87.0 -69.4 TRANS BOAT24 H39 -73.8 -25.4 68.2 CIS BOAT26N H6 73.3 -86.4 -69.0 TRANS BOAT26P H20 70.6 24.2 -67.4 CIS BOATaverage 69.2 66.7An interesting correlation between the biradical geometries and thestereochernistry of the major solid state product formed is apparent from Table XII. Forall diketones the 01 values remain close to the mean value 69.2°, with the exception of aslight deviation in the twelve and twenty two membered rings. However, a largedifference in 02 values can be seen between the pre-cis and pre-trans biradicalgeometries. It seems that the solid state photolysis of diketones stereoselectively affordscis-cyclobutanol derivatives and trans-cyclobutanol derivatives as the major productswhen the values of angle 04 are close to 25° and 87°, respectively.CHAPTER IV.4.0. Polymorphism, Solid-Solid Phase Transitions and Solid PhaseOrder Dependent Photochemistry of Diketones.As described in the Introduction, the polymorphic crystal modifications of organiccompounds can differ from each other not only in the packing arrangement of theconstituent molecules, but also in their molecular conformations as well. Furthermore,polymorphs with different conformers can exhibit molecular packing in the same spacegroup (conformational isomorphism)86 or in a different space group (conformationalpolymorphism).80a Such variation of molecular arrangements in crystal lattices for a givencompound may lead to significant differences in chemical behaviour. The effects ofpolymorphism on thermal or photochemical behavior cannot be fully understood unless therefined molecular structures of these crystal forms are known.When the molecules that build up the lattice pack differently with differentsymmetry relationships, they can undergo various intermolecular reactions uponirradiation. Several examples of polymorphs displaying such variations in bimolecularphotochemical reactivities in the solid state are recorded in the literature.184 The classicexample of polymorphic-dependent photoreactions would be the elegant work of Schmidtand co-workers on the polymorphs of the trans-cinnamic acid system.23 The reactivitydifferences between the three crystal modifications (trimorphic) of the cinnamic acidderivatives, as described earlier, were explained with the help of X-ray crystal structureanalysis as being the outcome of different crystal packing arrangements. An extensiveinvestigation into these systems in fact provided the foundation of the topochemicalprinciple.185113114Obviously, however, any reactivity differences between conformationalpolymorphs would be mainly the result of different molecular conformations. Sincemolecular conformations greatly influence unimolecular reaction mechanisms, irradiationsof conformational polymorphs may exhibit dramatically different unimolecular reactivityprocesses. In such systems, therefore, one can develop an understanding of the effects ofconformation on chemical reactivity.A striking example of conformational polymorphs dictating unimolecularreactivities is found in the divergent photo-behaviour of the two crystal modifications ofthe twenty-six membered ring diketone cyclohexacosane-1,14-dione (14),186 as describedearlier in Chapter III. The plates and needle crystals of diketone 14, upon irradiation atroom temperature, underwent stereoselective cyclization to yield predominant formationof cis (14c) and trans (14t) cyclobutanol derivatives respectively. The X-ray crystalstructure analysis confirmed the existence of the conformational polymorphism. As shownin Chapter III, significantly different molecular conformations are packed with spacegroup P21/n in plates and with space group P21/c in needles. The ORTEP packingstereodiagrams of the plate and the needle dimorphs and their corresponding cellparameters are shown in Figure 56.Only a few examples of conformational polymorphs displaying substantiallydifferent unimolecular reactivity are reported in the literature.57d, 167,168,169 To ourknowledge, only one other example of this type which is accompanied by a completeX-ray structure analysis has been reported,57d and this study was with a-adamantyl-p-chloroacetophenone (43). Compound 43 crystallized in two crystal modifications, needles(P21/n) and plates (C2/c). The irradiation of the needle forms gave 74% trans-cyclobutanol derivative 44 and 26% cis-cyclobutanol derivative 45, whereas irradiation ofthe plates gave exclusively the trans-cyclobutanol derivative 44 (Figure 57).a = 5.541 (2) Ab = 28.372 (2) Ac = 8.005 (2) A13= 98.89 (3)°P2iinmonoclinica)115b)a = 8.107 (2) Ab = 5.526 (2) Ac = 28.274 (3)A13 = 97.98 (1)°P2ikmonoclinicFigure 56: The ORTEP stereodiagram of unit cell packing of (a) plate (viewed from "a"axis), and (b) Needle (viewed from "b" axis) crystals of diketone 14.116 r\LA rtransC2/c biradical10/, A r cis -cyclobutanol formationseverely hinderedCI zP 21/n biradical^cisFigure 57: Solid state photochemistry of a-adamantyl-p-chloroacetophenone.The reactivity differences were explained based on the X-ray crystal structures. Inthis example, unlike in the twenty-six membered ring diketone, the geometries of the 1,4-biradical intermediates generated would be very similar in both crystal modifications (theunabstracted y-hydrogen and the hydroxyl group in the biradical intermediate are cis toeach other), except for the orientation of the plane of the aryl ring, and thus it might beexpected that least motion closure would lead to cis-cyclobutanol in both cases.However, in the plate crystals, it was suggested that the motions required to form the cis-cyclobutanol product are inhibited due to the substantial steric hindrance developedbetween the aryl group and the bulky adamantyl moiety.In our present study, the plate crystal modification of the twenty-six memberedring diketone exhibited an irreversible solid-solid phase transition behaviour. When theplate crystals were heated slowly on the hot stage of the Fisher-Johns melting point117apparatus (1°C min-1), the colourless transparent crystals cracked between 53-58°C, andbecame microcrystalline and then opaque.The differential scanning calorimetric analysis (DSC) of the plates (Figure 58)indicated the existence of an endothermic (AH = —6 kJ mol-1) solid-solid phase transitionat 54°C (in this experiment the temperature of the crystals was raised gradually from 30°Cat a rate of 2°C min-1). A broad endotherm corresponding to the melting point was alsoobserved at 69-70°C. The needle crystals on the other hand showed no solid-solid phasetransition on DSC analysis, but a sharp endotherm corresponding to the melting point wasobserved at 69-70°C. The annealed plate crystals (virgin crystals of the plate form whichhad been taken through the transition temperature or the melting point at least once andthen cooled to room temperature) interestingly showed a DSC thermogram identical tothat of the needles. The heating DSC thermogram of the annealed plates in the subsequentscans is reproducible regardless of the duration between each scan. Figure 58 representsthe DSC thermograms from the heating of the plates (Figure 58a) and needles (annealedplates) (Figure 58b) of diketone 14. Phase transition temperatures (°C), melting points(°C) and heats of transition (kJ mol-1) in parenthesis are included. The X-ray crystalstructure analysis of the annealed plate crystals could not be performed, due to theirphysical nature (rnicrocrystalline and opaque).The powder diffraction patterns obtained for the plate, needle and annealed-plateforms (Figure 59) at room temperature indicate that the crystal structure of the annealed-plates is similar to that of needles but different from that of plates. The diffractionpatterns of the needles and plates show peaks at quite different angles, whereas the patternof the annealed-plates is similar to that of the needle form. With regard to the positions ofthe peaks, the unit cell of the annealed-plates and that of the needles is identical. Asexpected, needle crystals were grown from a saturated solution of diketone 14 whenseeded with annealed plates.11820^30 40 SO^60^70 60 90 100(a) 10FECr0-10 —tp - 54°C (6.3 kJ mo1-1)-tp-20 — mp - 70°C (76.7 kJ mo1-1)-30 —-40 — MpTemperature (T)20^30 AO 50^60^70 SO 90 10010^tliiIIIIIIIIIIIII(b)-30-AOnip - 70°C (76.2 kJ mol-1)Temperature (°C)Figure 58. Differential scanning calorimetry thermograms of (a) plate and (b) needlecrystal modifications of 14. Phase transition temperatures (°C) and heats oftransitions (kJ mo1-1) in parenthesis are included.50.• 1•1•1•1•11•1•1•1•1•1•1•1•1•1•1•1`1•1•1•1•1•1•1•1•1•1•1•1•1`1•1•1•1•1•1•1•1•1•1•1•1•1.1•1•5.^10.^15.^20.^25.^30.^35.^40.^45.• I'1•1•1•1•1•1•1•1•1•1`1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•11•1•1•1•1•5.^10.^15.^20.^25.^30.^35.^40.^45.^50.11..1•1•1•1.1.1•1•1•1•1•1•1•1•1•1•1.1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1•1'1•1•1•1•1•1•1•1'1•1•1•1•1195.^10.^15.^20.^25.^30.^35.^40.^45.^50.^ 20 ^■Figure 59: The powder diffraction patterns obtained for the (a) plate, (b) needle and (c)annealed plate forms of 14 at room temperature.(a)•(b)(c)120A solid state Fourier transform infrared (MIR) analysis of the plate crystalmodification of &ketone 14 obtained as a function of temperature in KBr matrices showeda significant difference (especially in the fingerprint region 700-1500 cm-1) between thespectra taken below and above the transition point (54°C) as shown in Figure 60. TheFTIR spectrum of the needle crystals and a spectrum recorded for diketone 14 in carbontetrachloride (20°C) are also included for comparison. The spectra at high temperatureswere taken using a special KBr pellet holder, as described in the Experimental Section.The temperature of the sample was gradually increased and the spectra were obtained at20°C, 55°C, 60°C and 65°C. All the sharp bands observed in the spectra of the platecrystals are completely replaced by a new set of sharp bands at the high temperature solidphase, and interestingly, the spectra obtained above the transition point are practicallyidentical to the spectrum of the needles and annealed-plates (major changes observed inthe spectra are illustrated in Table XIII, using the frequency of the bands as a function oftemperature). The above analysis explains the existence of a single new conformation inthe high temperature solid phase, presumably the zigzag conformation observed in theneedle crystal forms. For needles and annealed-plates, the spectra remained unchanged atall temperatures.From these results, it seems that, at the transition point, the metastable lowtemperature solid phase (plate forms) is irreversibly transformed into a high temperaturesolid phase, and upon cooling, this phase, which is presumably the needle form, remainsstable at room temperature. Although dimorphs are usually known to melt at differenttemperatures,88 in diketone 14, not surprisingly, both plates and needle crystalmodifications have identical melting points, and this becomes an additional evidence forthe transformation of plate crystal forms into needles at the transition point.110 K.1y l;143 311(a)1213200^2440^2000PY 114 -yrI.14 •(b)1- cm-1 -40,I ;I;11!IIft■^I10■ 46636-41 C.:433209 2440 MS^16,0^1 zee^seaFigure 60: The solid state FTIR spectra of (a) plates at 20°C, (b) plates at 60°C and (c)needles at 20°C in KBr matrices. d) A solution spectrum of diketone 14recorded in CC141 17f2400^.2see122'11^Itee St.ve#4.96.9117.2?77.6567.9040.7126.0729 4319 703200(d)014'1jure. "3r^I96 9107 27 --77 63 -67 99a)c.)co^se 35p40.71 -C39 1729.4319 79 -(c)123Table XIII: FTIR band frequencies (cm-1) of annealed plates, needle crystals and low andhigh temperature solid phases of plate crystals as a function of temperature.PLATES (20°C) PLATES (65°C) ANNEALEDPLATES (20°C)NEEDLES (20°C)16981703 1703 170414711463 1464 14631433 1433 143314141409 1409 140913741365 1365 136512141199 1199 12001154Further evidence to support the nature of the high temperature solid phase and theirreversible solid-solid phase transition observed in diketone 14 came from the type IIphotochemical investigations of both the plate and needle crystal modifications as afunction of temperature.Researchers have widely used the type II photoreactions of ketones to probe thesteric and electronic microenvironments provided by a variety of ordered media.157,162,187-189 Since the conformational requirements of the initial y-hydrogen abstractions andthe closure or cleavage of the biradical intermediates into products are specific, an124investigation of type II product distributions in various phases provides valuableinformation regarding the order of the media. In fact, these results can be correlateddirectly to the motional freedom of the molecules provided by the phase. Because the fateof a biradical intermediate following the y-hydrogen abstraction depends on the flexibilityof the cavity wall and the free volume present inside the cavity, information regarding thecharacteristics of the reaction cavities (size, shape and rigidity) occupied by the molecules(electronically excited ketones or the biradical intermediates) can also be obtained fromthe photochemical results.Several examples of type II photochemical investigations of guest ketones invarious liquid-crystalline phases provided by host compounds are recorded in theliterature.157,162,188,189 Liquid-crystals are generally known to exhibit various phases,which can provide a variety of constrained environments capable of directing the motions,the conformations and the reactions of the guest ketone molecules, thus influencing thehigh selectivity differences in the photochemical reactions of these ketones in variousphases. The product distributions can therefore be used to measure the influence of thephase order on the course of the reaction. However, only a few examples of type IIphotochemical investigations on neat ketones in their various solid phases are known. Arecent publication on the type II photoreactions of trans-1-(4-pentanoylpheny1)-4-pentykyclohexane (46) and trans-1 -hepty1-4-(4-pentanoylphenyl) cyclohexane (47)(Figure 61) in their various solid, liquid-crystalline and isotropic phases clearly illustratesthe influence of the phase order on the product distributions.189a In this study, thedifferent phase orders investigated by deuterium NMR spectroscopy and differentialscanning calorimetry correlated well with the photochemical results.The high reaction stereoselectivity for diketone 14 at 20° C has been explained asbeing the result of the motional restraints imposed by the lattice. Thus, as describedearlier in Chapter III, a rigid reaction cavity with a very small free volume in this highly125anisotropic medium may limit the motions severely, and therefore the least motion closureleads to either cis or trans-cyclobutanol derivatives, depending on the conformation. Therelatively large motions involved with the fragmentation processes would correctlyaccount for the formation of very small amounts of cleavage products.CH3(C(n = 4)^46(n = 6)^47Figure 61: trans-1-(4-Pentanoylpheny1)-4-pentylcyclohexane (46) and trans-1 -hepty1-4-(4-pentanoylphenyl) cyclohexane (47)In addition to the reaction at 20°C, irradiations of the two crystal modifications ofdiketone 14 were conducted at 0°C, 40°C, 60°C, and 65°C. The product percentages arecompiled in Table XIV. The product percentages from the annealed plates (20°C) andhexane (20°C) solution are also included for comparison.Irradiation of plate forms above the transition temperature (54°C), at 60°C and65°C showed a dramatic reversal in the stereoselectivity of cyclobutanol formation.However, throughout the low temperature solid phase (below the transition temperature),the reaction was quite similar to that observed at 20°C (stereoselective formation of thecis-cyclobutanol 14c). At all temperatures, irradiation of the needle formsstereoselectively gave trans-cyclobutanol derivative 14t, but the selectivity was slightlylowered with increasing temperature. The product ratios of the plates above the transitionpoint were comparable to those of the needle crystals. Interestingly, the photo-behaviourof the annealed crystals was identical to that of the needle forms, at all temperatures, and126these results correlate well with the DSC and FTIR analyses. This clearly suggests theirreversible nature of the solid-solid phase transition of the plate crystal form into theneedle crystal form at the transition temperature (54°C).Table XIV: Product percentages of diketone 14 from (a) plates, (b) annealed plates,(c) needles and (d) isotropic media (hexane) as a function of temperature., temp (°C) medium cis (%) trans (%) cleavage (%)a00 Plates 99 01 0020 Plates 97 03 0040 Plates 96 04 0060 Plates 19 81 0065 Plates 20 76 04b 20 Annealed Plates 09 91 00c00 Needles 07 93 0020 Needles 09 91 0040 Needles 11 89 0060 Needles 18 82 0065 Needle 17 83 0020 Solution (hexane) 14 33 53The high stereoselectivity above the transition temperature, although slightly lowerthan that observed below the transition point, indicates the anisotropic nature of the hightemperature solid phase. Presumably the characteristics of the reaction cavities above thetransition points may resemble those of the low temperature solid phase. However,127inherently larger vibrational and rotational motions of the molecules at high temperaturemight be the reason for the slightly lowered selectivity.Several years ago Schmidt et al.25 observed a similar irreversible solid-solid phasetransformation in the trans-cinnamic acid system and investigated the nature of thetransformation with the help of characteristic phase-dependent photobehaviour andpowder pattern analysis. Although the photoreaction involved was an intermolecular[2+2] dimerization, the phase-dependent photobehaviour is somewhat similar to thatobserved in diketone 14. The trans-cinnamic acid underwent an irreversible solid-solidphase transformation around 50°C from the metastable [3-form into a stable a-form; thetransformation, however, seems to be quite slow compared to that of diketone 14. As wehave described in the Introduction, room temperature irradiation of the a-form causesdimerization to a-truxillic acid and of the 13-form to 13-truxinic acid. However, the type ofproduct formed from the 13-form depends on the temperature, due to its phasetransformation behaviour. At temperatures higher than —50°C, irradiation of [3-form gaveboth a-truxillic and 0-truxinic acids. The product ratios were found to depend on thetemperature and the duration of exposure of the 0-form crystals to that temperature, asillustrated in Table XV. As suggested by Schmidt, a-truxillic acid is formed via the 13-3aphase change at temperatures higher than 50°C.In an attempt to examine the molecular motions involved in the high temperaturesolid phase, Fyfe et al.192 have investigated diketone 14, in its various forms, using13C cross-polarization 'magic angle' spinning experiments (13C CP/MAS). The 13CCP/MAS spectral results have been analyzed and provided by them. Figure 62 (a and b)represents the 13C CP/MAS spectra obtained for the plates at 27°C and at 57°C (belowand above the transition temperature). For comparison, the solution 13C NMR spectrumrecorded in hexane is included in Figure 62c.128It has been indicated that the large spinning side band (-200 ppm, Figures 62a and62b) pattern for the carbonyl region is a result of the large chemical shift anisotropy(CSA), which denotes the static nature of the carbonyl groups in both the low and hightemperature solid phases.Table XV: Photochemical results of p -form cinnamic acid as a function of temperature.Temperature (°C) Irradiation time (hr) a-form (%) 13-form (%)25 100 100 0045 09 100 0051 50 50 5064 02 50 5064 04 00 100I^IIN III^7^1^If -1- ,^,2119 INPPM.1•2!":PPP^V SISX112Ma 220^200^120^150^140^120^100^20Figure 62: 13C CP/MAS spectra of plates a) at 27°C and b) at 57°C, c) 13C NMRspectrum of diketone 14 in hexane.The annealed plates and needle forms also show large CSA for the carbonyl regionat 27°C. The restricted motions clearly explain the anisotropic nature of the low and hightemperature solid phases. These results correlate well with the photochemical results(high stereoselectivity of the cyclobutanol formation) observed in both the low and hightemperature solid phases. Interestingly, the patterns of the peaks corresponding to themethylene region of the spectra, although complicated, look the same in all situationsexcept in the case of the plate form at 27°C (below the transition point), which is quitedifferent from the others (Figure 63). This is additional evidence that the plate formundergoes irreversible transformation into the stable needle form at the transition point.129(c)130 20 080 60 40 20 0 40(d)PPm 80^60 40^20 0PPrn 80 6040 20 0Figure 63: The aliphatic region of diketone 14 in 13C CP/MAS spectra from (a) plates at27°C, (b) plates at 57°C, (c) annealed plates at 27°C and (d) needles at 27°C.131The sixteen membered ring diametric diketone (9), eighteen membered ringdiametric diketone (10) and sixteen membered non-diametric diketone (15) also exhibitedenantiotropic solid-solid phase transitions, but unlike the one observed in diketone 14,these phase transitions were reversible in nature. Upon heating, a low temperature stablephase was transformed into a high temperature metastable phase, and upon standing atroom temperature the high temperature phase reverted back to the low temperature stablephase. In all cases, when the transparent crystals were gradually heated from roomtemperature, they became microcrystalline as they passed through the transitiontemperature and then became opaque. The DSC thermograms shown in Figure 64illustrate the heating of diketones 9, 10 and 15 at 2°C min-1. The phase transitiontemperatures (°C) and heats of transition (kJmo1-1) in parentheses are also shown.The phase behaviour of diketones 9 and 10 were reported by Dale et al., but ourreproducible transition temperature of diketone 9 (34°C) measured from DSC did notcorrespond exactly with the published value (28°C).103 Strikingly, diketone 15 has twotransition points below the melting point, whereas the others have only one. The heatingthermograms in Figure 64 can be reproduced with the same endothermic heats oftransition in subsequent scans, irrespective of the time lag between each scan. The heatingcurves of the annealed crystals were also not dependent on whether the virgin crystal washeated through the transition point or through the melting point. This indicates thereversible nature of these solid-solid phase transitions. The X-ray single crystal structureanalysis of the annealed crystals could not be performed, for the same reason mentionedwith regard to diketone 14.The infrared spectra of crystals of diketone 9 were recorded in KBr matrices atvarious temperatures above and below the transition temperature (20°C, 35°C, 40°C,50°C, 60°C, 70°C).-10-10132(a) 20 30 40 60 60 70 80 90 1006 1^1^i^1^1^1^1^1^1^1^1^1^1^1^1^1tp - 34°C (6.3 la moi-1)mp - 86°C (11.7 kJ mol-1)tpmp-15(b)Temperature (°C)20 30 40 SO 60 70 SO 90 10050—tp tp - 86°C (12.1 kJ mol-1)mp - 96°C (29.7 kJ mo1-1)(C)-15—-20—mpTemperature (°C)20 30 40 50 60 70 80 90 1005 1^1^1^1^1^1^1^1^1^1^1^1^1^1^i^1lst tp^mpVt _4, 37°C (23.6 kJ mo1-1)tp - 55°C (7.8 kJ mo1-1)mp - 77°C (8.1 kJ mol-1)-15Temperature (°C)Figure 64: Differential scanning calorimetry thermograms of a) diketone 9, b) diketone10, and c) diketone 15. Phase transition temperatures (°C) and the corresponding heats oftransitions in paranthesis (kJ moll) are included.133The spectra of the low temperature solid phases are significantly different fromthose of the high temperature solid phases, especially in the fmgerprint region (700-1500 cm-1). As the temperature of the crystals passed through the transition point, thebands became broader and the spectra, which became practically identical with thatobtained in solution, remained unchanged throughout the high temperature solid phase.The FTIR spectra of diketone 9 obtained at 20°C, 35°C, 40°C are shown in Figure 65.The solution spectrum recorded in carbon tetrachloride at 20°C is also included forcomparison.Dale103 observed a similar broadening of the sharp bands for diketone 9 (abovethe transition point) and suggested a more or less flexible low temperature solid stateconformation,103 but he did not rule out the possibility of contributions from other lowenergy conformations,99a a situation generally accepted for isotropic liquid media. Thepattern of the spectra obtained at 35°C, slightly above the transition point, indicates asituation between the low and high temperature solid phase. This rules out an instantphase transition at the transition temperature 34°C. Unlike the diketone 14, the annealedcrystals of diketones 9, 10 and 15 behaved exactly like the virgin crystals in all aspects.Although FTIR analysis reconfirmed the reversible nature of the phase transition,the nature of the metastable high temperature solid phase, which produced an infraredspectrum similar to that of the isotropic medium (20°C), intrigued us into further analysis.To explore this, a detailed temperature dependent photochemical investigation of thesediketones was undertaken. Virgin crystals were photolyzed as a function of thetemperature above and below the solid-solid phase transition temperatures. Irradiationswere also performed in the isotropic medium (all reactions were conducted in hexane,except the irradiation of diketone 10 at 90°C, which was carried out in octane). Theproduct percentages, as a function of medium and temperature, are shown in Table XVI.400ouu #,-4,00^AMUima1600 1 2ilif!11134'111.T:' I^'; ri, lir,^Illr II,I j ..^;ri^1!;; T';' 11 1 ,:. ,^I^I, ',,,op,,I^II! ,1,^1 Ill^11'11 llil 1111111,1 11,11 1,^li II!^!III !I' l' '^1.r. , ,,,,f 1^i; ,. ;1,',^II 1,: r —1 I I^I;rI IIH'II!,^;;;, ':;,,,^. ',, '^.' ! ; I,I,1!^1t.-,!10 ze ,^,,, atio(1., '' ;, ,,^I,^, , ;^, 1;^,... ,fr' ■^.^,^! ,9'.1.I,i'11I!i,^;il11^;if 1.1^t,'^I1 1 1 i 11^. 11^I^1 I 11 ; i I t !,^I,1!^,',.I1II!1II^!1III,I^!III,'!!^I!,^1;!^I^1 r:1II ,1!!I,I:!'!1!!'^II^Ilc,'!I'ilII'III^rl!^1 I,^I1I^1III,!1:II1,i'!.!!I :1 !^1 !!!^I ! I^.^i!^! 1I 1; 1'7 71^'^.,II,,,1^i,I'!1'1I^I III^■It^III^1'^I,1 "^I,;,^,„ •''I.,,i.^111,1^.,Iii i^' r ,^. !^, ]^it ;.:rJill ui i^!^i24rea^at**!,41:.„, ,,,!'!I frif)4S!Iii!,^I1.ill14 b■■,,,'„6:-1^1-r99i i,"- i^.„.^, ,-' 11, i. t til.k1 II : '11' '^'^1 H l'1', '^11 t',^, 1.^i , ■^i il^■1^'I :r^1, ,i i^'. II^I, .^1 Ili! '1 l''''''', !II1,I l':;It': 'f.1r 1^1 1[111! li,^11! ' H. 1: . ,^I IH: :II'. ''. I;It.,1II^! HII^;1.^l';IIII^.^i'.,^I^!III':','1^'';^'I-'I,^,1 1^;^.,':1,11 ^WI'^;I,11,I1!i^l^!:!i'II;10^1It'!;'!tr1i71,'rriII I;^,^.li,^,^1.-.1:,^;,;^':'11.^, ;^I , i ,r'IVILL, ,'^i i.';',1'''i^114•:, ,.:,i- 4■..1.lIfIr+—r ,^-f^-r i -(a)3f 45491644' 1(b)135IFigure 65: The solid state FTIR spectra of diketone 9 recorded at (a) 20°C, (b) 35°C,(c) 40°C in KBr matrices. (d) A solution spectrum of diketone 9 recorded in CC14.136Table XVI: Product percentages of diketones (a) 9, (b) 10, and (c) 15 as a function oftemperature and medium.(a)Temp (°C) SOLID STATEcis(%)^trans(%)^cleavage(%)HEXANEcis(%)^trans(%)^cleavage(%)00 89 08 0310 90 07 0320 89 10 01 22 35 4330 47 16 37 21 32 4740 17 20 63 19 30 5160 20 21 59 18 28 5420(Annealed) 86 10 04(b)Temp(°C) SOLID STATEcis(%)^trans(%)^cleavage(%)HEXANEcis(%)^trans(%)^cleavage(%)20 03 84 13 17 42 4130 03 82 15 24 38 3840 03 81 16 23 36 4160 04 79 17 23 32 4580 06 75 19 22 31 4790 13 49 38 21 30 49Annealed20 03 81 16137(c)medium, temp (°C) cis cl cis c2 trans^ti + t2 cleavage el+e2HEXANE 30 13 13 35 39CRYSTAL 30 98 02 00 0040 20 09 33 3860 14 13 26 47Annealed 30 98 02 00 00The highly stereoselective cyclobutanol formation observed at room temperaturepersisted throughout the low temperature solid phases, but interestingly, above thetransition points, the stereoselectivity was completely lost and the ene-dione cleavageproducts predominated accompanied by lesser amounts of cis and trans-cyclobutanolderivatives. The product distributions in the high temperature solid phases are comparableto those in the isotropic medium. Almost constant and temperature-independent productratios were observed in solution at all temperatures, as observed for diketone 14.Furthermore, the irradiation times required to achieve equal percents of conversions werequalitatively much shorter in the isotropic and high temperature solid phases than in thelow temperature solid phases. The influence of the phase on the product distribution seemto be negligible in high temperature solid phases, whereas it is significant in the lowtemperature solid phases.In the case of diketone 15, only a slight variation in the product ratios could beseen between the two high temperature solid phases; still, the selectivity observed at roomtemperature remained unchanged up to the first transition point, but beyond thistemperature, the selectivity was reduced and the results were quite close to those insolution. In the high temperature solid phase the anisotropic packing order must be138largely absent. It appears that the high temperature solid phases mimic the situation insolution. The FTIR results observed for the high temperature solid phase of diketone 9further support this result. The high stereoselectivity of the cyclobutanol formation in thelow temperature solid phases is in fact somewhat similar to that observed for diketone 14.Thus, a similar argument would correctly explain the selectivity. However, the loss ofstereoselectivity and the large amounts of fragmentation product in the high temperaturesolid phases indicates the existence of larger motional freedom. The reaction cavities inthe high temperature solid phases must have very flexible cavity walls with large freevolume, especially around the reaction center (or the biradical moiety) of the diketone.When large free volumes are available in the reaction cavity, conformational isomerizationof the biradical intermediates or the electronically excited diketone is possible.It is generally accepted that the cisoid or gauche 1,4-biradical intermediates affordlarger amounts of cyclization products, and the transoid or anti biradical intermediateslead exclusively to elimination products. In the case of the cyclic ketones, the gauchebiradical intermediates are topochemically favoured, and therefore, in an anisotropicmedium such as the low temperature solid phases, the biradical intermediate formed wouldprefer to close rather than to cleave, and this was observed experimentally. But in hightemperature solid phases, owing to the isotropic nature of the medium, the flexiblereaction cavity wall and the large free volume may allow even the gauche biradicalintermediate to undergo larger conformational changes, which is generally accepted to benecessary for the fragmentation process.Our insights into the motions involved in the high temperature solid phases ofdiketones 9 and 10 were investigated by Fyfe et 0.192 using 13C CP/MAS and wide-linedeuterium NMR (2H NMR) spectroscopy (the ketones fully deuterated in the methylenepositions a to the carbonyl groups). All solid state spectra and their analysis wereprovided by Fyfe et al.139Figure 66 represents the 13C CP/MAS spectra obtained for diketone 9 at 27°C(below the transition temperature) and at 37°C (above the transition temperature). The13C NMR spectrum obtained in an isotropic medium (CDC13) is also included forcomparison. In Figure 66a, from the large CSA (— 200 ppm) associated with the carbonylsignals, it is apparent that the carbonyl groups are either static or their motions are largelyrestricted at 27°C. A similar large spinning side band pattern is observed at lowertemperatures. In the methylene region (the expanded methylene region is shown inFigure 67), the sharp signals with CSA close to 100 ppm suggest that the methylenecarbons corresponding to these peaks (likely the a carbon atoms) have very limitedmotions.Interestingly, just above the transition temperature at 37°C (Figure 66b), thespectrum is significantly different from the one obtained at 27°C, but as expected, it looksquite similar to the 13C NMR obtained in the isotropic medium (Figure 66c). The foursharp signals in the methylene region (as observed in the isotropic medium) correspond tothe four different methylene carbons present in an individual molecule. At 37°C thepresence of a single carbonyl resonance, as opposed to the two peaks observed at 27°C(consistent with the pseudo C2 molecular axis of symmetry of the solid stateconformation), together with the four sharp peaks in the methylene region, indicates thehigh molecular symmetry, and is due presumably to either the molecular motions or thepresence of an inherently highly symmetrical molecular conformation above the transitionpoint. From the reduced spinning side band pattern (-70 ppm) of the carbonyl groups at37°C (Figure 70b), it has been concluded that they are no longer static, but the finite widthof the side bands rules out any isotropic motion.(a)140(b) r etNE,!141(c) •!"^: ■tPle V IMMO104-'Ppm 220 200^180^160^140^120^100^80^60^40^20^0Figure 66: 13C CP/MAS spectra of diketone 9 at (a) 27°C, (b) 37°C, and c) a solution13C NMR recorded in CDC13.1^ 1^•1^1BO 70^68^58^40^30^20^10^S —18 —20^-38PPMFigure 67: The expanded methylene region of diketone 9 at 27°C (13C CP/MAS).142In order to obtain a more detailed picture of the order experienced by the diketone,solid state 2H NMR studies were performed on the a-deuterated ketone 9-d8. 192a Thedeuterium NMR spectra of a sample fully deuterated at the a positions with respect to thecarbonyls were obtained at 27°C and 37°C (Figure 68).a)b)44t^1 MUM^SIMS^11^-50111111^-1555,5I^I^i^I^T^1^111 ^1^1^1^1^1^1^1^,^I^-r^I^I^v 1N ER 7 ZFigure 68: 2H NMR spectrum of diketone 9 (a) at 37°C and (b) at 27°C.143The observed quadrupolar splitting provides information on the restrictions thatphase order imposes on the motions of the C—D bonds. 192b The classic Pake powderpattern with the quadrupolar splitting (Av – 120 kHz) close to the value of a rigidmolecule (127.5 kHz193) observed at 27°C (Figure 68b) and a narrower peak in the hightemperature solid phase at 37°C (Figure 68a) have been explained as indicating the fairlystatic nature of the C—D bonds at the a-methylene groups at 27°C, compared to the hightemperature phase. The magnitude of the quadrupolar splitting also suggests that theC—D bonds experience a large degree of phase order. The above two experiments ondiketone 9 clearly indicate that the carbonyl groups and the a methylene C—D bondsexhibit a large degree of motion in the high temperature solid phase, compared to that inthe low temperature solid phase at 27°C. A 180° ring ffip or internal bond rotations of themethylene groups have been suggested to explain the type of motions involved.These results, correlate well with the observed photochemical results. The largemotional freedom observed in the high temperature solid phases, presumably due to thehighly flexible nature of the reaction cavity with large free volume, clearly explains thesolution-like photobehaviour. As observed in diketone 14, the anisotropic nature of thelow temperature solid phase would favour the least motion pathway to afford thestereoselective cyclization.However, in the case of diketone 9 in the low temperature solid phase just belowthe transition point (30°C), the product distribution observed does not represent thetypical ratios of either the low temperature or the high temperature solid phases. Theproduct ratios indicate that limited molecular motions are available, but which are still notcomparable to the motions available in the high temperature solid phase or the isotropicmedium. The formation of large amounts of the presumably more strained cis-cyclobutanol, when compared to its diastereomer, the trans-cyclobutanol, resembles a144situation in between the low and high temperature solid phases. Interestingly, the13C CP/MAS spectrum obtained at 32°C (slightly below the transition point) suggests thepresence of small amounts of both phases (Figure 69). Although the photochemicalinvestigation of diketone 9 was performed at 30°C, the temperature variation of ±2°Cprobably would satisfactorily explain the product distribution observed at 30°C.I321^'31O^281^261^241^221^211^III^IBS^lid^121^liePPMFigure 69: 13C CP/MAS spectrum of the carbonyl region of diketone 9 at 32°C.13C CP/MAS (Figure 70) analyses of diketone 10 above and below the transitionpoint reveal that the carbonyl group remains conformationally static in both the low andhigh temperature solid phases; however, the spectra indicate that the methylene chainsundergo rotational motions in the high temperature solid phase. As shown in the13C CP/MAS spectra (Figure 70), the spinning side band pattern of the carbonyl groupremains unchanged in both phases, which indicates that they are not involved in themolecular dynamics of the high temperature solid phase. At 92°C, the slightly lowerintensity of the spinning side bands of the methylene carbons compared to that observed at510 -SO311-^241 201^t51PPM(b)CSA - 200 ppmmethyleneside bandsCSA - 200 ppmmethyleneside bands14527°C, has been suggested as an indication of slightly motionally averaged methylenegroups in the high temperature solid phase.(a)"^ '^1^1^1^'^1^ 11300^250 211 1 SO III 5^ —SOPPoi1220^200^lao^I ^ '0^140^120^100 80I•••••"• 1•"•••• '1." •^'60^40^20^0 PPM1240I ' • • • I146( c )02111401 XL -3003c OBSERVE7473 MA SE SECUDICE 100130DATE 111-05-61500 005? CDCL 3FILE CACOu1SITIOM^DEC • vlTN^13 750 DM^I 750:7^30000 0 D 350 .1^0 400 Du^TV,W^16000 DuM SWY 12 0 OW^6700TI 0 MO MDi^0 400 OLP...."07TO^7000 IMIOCESSIMGW 1000 SE^0414Cl^1000 LO i 2230^ ISO^II 0 EN^05336IS 500 IMAIN^6SS 0IL^hi^DISPLAYIN 1 SP^-703 7ON^r^V 200000MS WI VS^200SC ,,,,,,VC^400IS 500WI.^6511 aNET 51106 0Tor^131INS 1 000DC 1•4741 Figure 70: 13C CP/MAS spectra of diketone 10(a) at 27°C and (b) 92°C. (c) A solution13C NMR spectra of diketone 10 recorded in CDC13.The 2H NMR spectra of the oc-deutrated diketone 10-c18 (Figure 71) indicate thatthe C-D bonds exhibit larger motions above 82°C, even though the transition temperatureis 86°C. This discrepancy may again be due to the temperature gradient. The motionalfreedom observed in the high temperature solid phase can correctly account for thephotochemical results. Diketone 10 seems to exhibit substantial motions in the hightemperature solid phase, especially in the methylene region of the molecules.Although solid state NMR spectroscopic analysis of diketone 15 was notperformed, in the high temperature solid phases one can presume a situation similar to thatobserved in diketones 9 and 10. Interestingly, in diketones 9 and 10, the solid statespectroscopic analysis performed for the annealed crystals gave the same results asobtained in the virgin crystals; this provides an additional piece of evidence for thereversible nature of the solid-solid phase transitions in these compounds.a)b)147 11 1 111^II-1118188I^II^II^1^I^i^1^1-^7^1^1^1611800 HOBO eWERT Ii-511000Figure 71: 2H NMR spectra of diketone 10 (a) at 82°C and (b) at 27°C.The solid state spectroscopic (13C CP/MAS and 2H NMR) results of dilcetones 9,10 and 14 correlate well with the photochemical results, as far as the motional freedomhv(CI-) ^(C142)(31')(32')0)).1H IIII^. • IPIIIIHH111^H(C H2) ^(CH Hi^til1Hn . 5 (31)n = 9 (32)(CN)1)^(CHA(31a)(32a)148CHAPTER V5.0. The Photochemistry of Alkylated Cyclic Diketones.Irradiation of the tetramethylated sixteen membered ring diketone2R*,8S*,10R*,16S*.4etramethylcyclohexadecane-1,9-dione (31) and the twenty-fourmembered ring diketone 2R*,12S*,14R*,24S*-tetramethylcyclotetracosane-1,13-dione(32) in the solid state and in hexane yielded products derived exclusively from the Norrishtype I reaction.10,62 Even though the non-alkylated counterparts, the sixteen (9) andtwenty-four (10) membered ring diketones, upon irradiation, undergo efficientintramolecular y-hydrogen abstraction (type II reaction), the substitution of one of the twoa-hydrogen atoms by a methyl group (at least four methyl groups in each molecule)completely changes the reaction pathway and leads to photoepimerization.194 As depictedin Figure 72, the photochemistry of the tetramethylated diketones involves an initiala-cleavage generating a type I biradical intermediate (31' or 32'), followed by a reclosurewith inversion at the a-carbon atom.Figure 72: Photoepimerization of tetramethylated diketones in the solid state.149Unexpectedly, the stereochemistry of diketones 31 and 32 was the one in which allfour methyl groups are positioned on the same side of the ring. The ORTEPstereodiagrams of both diketones obtained by X-ray crystallography are shown inFigure 73.In both alkylated diketones, the solid state conformations have rectangular [3x3x]carbon frames, as observed for the corresponding non-aLkylated diketones. The7-hydrogen atoms with short 0—H contacts are indicated by dotted lines. The7-hydrogen atoms of diketone 31 H4, H4' (d = 2.89 A, co = 61.5°, A = 63.8°, 0 = 116.6°),H8, H8' (d = 2.71 A, co = 56.8°, A = 78.7°, 0 = 112.5°) and diketone 32 H16,H16' (d =2.64 A, co = 55.0°, A 83.6°, 0 = 117.2°) are ideally situated for abstraction by thecarbonyl oxygen atoms (as observed in the other non-alkylated diketones); however, notype II products were obtained from solid state irradiation.Solid state photolysis of diketone 31 to –30% conversion afforded only one majorproduct, diketone 31a (2R*,8R*,10R*,16S*4etramethylcyclohexadecane-1,9-dione),whereas in hexane, two major photoproducts at retention times 12.3 mins (diketone 31a)and 13.1 mins (product not isolated), were observed on GLC in a ratio of 6:4, with aminor product 31b (RT 10.8 mins). The solid and solution photolysis of diketone 32 to–30% conversion gave only one major product, diketone 32a (2R*, 12R*, 14R*, 24S*-tetramethylcyclo- tetracosane- 1,9-dione). On GLC, diketone 32a has a retention timeidentical to that of the starting diketone 32, and the reaction progress was thereforemonitored by analytical HPLC. The structures of the photoproducts were determined byspectroscopic analysis, mainly by comparing their spectra with those of the startingdiketones.The 13C NMR and APT spectra of diketones 31 and 32 indicate the presence offour equivalent methyl (16.7 ppm) and methine (44.6 ppm) carbon atoms. The spectralanalysis of photoproducts 31a and 31b indicates that both are diastereomers of thestarting diketone 31. 13C NMR and APT analysis of 31a reveal that all four methyl and150methine groups are in different chemical environments. The only possible structure withfour non-equivalent methyl and methine carbon atoms is that of 31a (Figure 72).Photoproduct 31b has all four methyl (16.5 ppm) and methine (45.6 ppm) carbon atoms inthe same chemical environment as does the starting diketone, but the chemical shifts areslightly different. Possible structures for diketone 31b are 50 or 51 or 52 (Figure 77), butthe stereochemistry of 31b was not determined.As previously mentioned in Chapter III, the photochemistry of non-alkylatedmedium and large ring cycloalkanones is dominated by y-hydrogen abstraction as theprimary photochemical process for both the 1(n n*) and 3(n 70`) excited states.Concomitantly, the products resulting from primary a-cleavage photochemical reactionsare virtually absent. In contrast, for small rings up to cyclooctanone, the dominantprimary process in solution photolysis is a-cleavage,195 rather than 'y-hydrogenabstraction. Irradiation of cyclononanone, however, affords only the reductionproduct.130 The preferred a-cleavage reactions of small ring systems have been studiedextensively with respect to both the primary process196,197 as well as the factors thatinfluence the behaviour of the acyl alkyl biradical intermediate. 198,199 The evidenceindicates that the triplet state is more reactive than the singlet state and that the rateconstant for a-cleavage increases with the relief of ring strain and the presence of radicalstabilizing a-substituents. 196,200Cyclododecanone undergoes smooth 'y-hydrogen abstraction upon irradiation incyclohexane, whereas 2-methylcyclododecanone (53) has been shown to undergo botha-cleavage and 'y-hydrogen abstraction to give type I (54 and 55), and type 11 (56, 57, 58and 59) products respectively; however, the a-cleavage products dominate (Figure 74).201The preference for a-cleavage over y-hydrogen abstraction was explained by the fasterrate of a-cleavage due to the stabilization of the biradical intermediate by the methylsubstituent.201 This explanation has been further supported by Turro et al202 in theirrecent study of trimethylated and tetramethylated cyclododecanones.(32)1122••• HI ••C I •C1311231121toCa• C3113H16'114HZ• : •C4115C5HT 116• 1ilt •119•••C6 CT.^• 1110• (II11131112C6•H4' 1115CS• 111441. 1117• •C11•••40 11191116C14• 125112411,fa,^toC12•••^•-■^ton• ilk • '1•,7•• F,IH26(31)11221118C1411251124H15C911141113H2115116119C6CT11101111CIO11161116151Figure 73: The ORTEP stereodiagrams of the sixteen membered ring diketone2R*,8S*,10R*,16S*-tetramethy1cyclohexadecane-1,9-dione (31) and thetwenty-four membered ring diketone 2R*,12S*,14R*,24S*-tetramethy1-cyclotetracosane-1,13-dione (32)152The photochemical reactivity of 2,2,12-trimethylcyclododecanone (60) and2,2,12,12-tetramethylcyclododecanone (61) in cyclohexane is exclusively type I (Figure75), with regiospecific a-bond cleavage (on the more substituted side) for thetrimethylated compound. These results clearly demonstrate that alkyl substitutionfacilitates the a-cleavage reaction. In another study,203 irradiation of 2-phenylcycloalkanones (62) (Figure 76) and 2,n-diphenyl cycloalkanones (n = ring size)with ring sizes ranging from ten to fifteen also yielded a-cleavage reaction productsexclusively. In these arylated cyclic ketones, the biradical intermediate formed by a-cleavage is much more stable than that from 2-methylcyclododecanone 53. Therefore, afaster rate of a-cleavage has been suggested as the factor responsible for the exclusiveformation of type I products from 2-phenylcydoalkanones 62 and both type I and type IIphotoproducts from 2-methylcycloalkanones 53.As described in the Introduction, the products resulting from photochemicala-cleavage are determined by the competing intramolecular reactions (recombination,disproportionation, decarbonylation) of the type I biradical intermediates. 196,197 It hasbeen found that the recombination process of the type I biradical intermediate is generallyefficient and often dominates.203 The reclosure reactions cannot be studied in allcompounds, since in most cases the reclosure products cannot be differentiated from thestarting ketones. Therefore, the quantum yields of these reactions do not necessarilycorrelate with the efficiency of the primary a-cleavage process . Unlike the alkylated andarylated cyclic ketones studied in the past, our "all cis" diketones appear to be goodmodels for studying reclosure reactions in cyclic compounds.In larger than twelve membered cyclic ketones, such as the alkylated diketones 31and 32, where 7-hydrogen abstraction is generally favoured, one would expect both type Iand type II processes as was observed in the case of 2-methylcyclododecanone. However,the results from diketones 31 and 32 clearly show that the formation of the type I biradicalintermediate is much faster than that of type II biradical intermediate. Even in the non-hv0^0\\CH^ZZI vCH(CF(R H)^( 60 )(R = CH3) (61)hv(CI-F12)7153alkylated medium and large membered cyclic diketones, the lack of type I products may bedue to the rapid reclosure of the type I biradical intermediate rather than to the completeabsence of a-cleavage primary processes.1—°E1 liirl/jjr+HL  (53)^(54)^(55)^(56)^(57)^(58)^(59)Figure 74: Type I and type II products from the photolysis of 2-methylcyclododecanone.(CH2)7^s (CH2C7Figure75: Photolysis of tri- and tetramethylcyclododecanone.154+62 (n = 10, 11, 12, 15)Figure 76: Photolysis of 2-diphenylcycloalkanones.Interestingly, a preliminary photochemical investigation of (R*, S*)-2,12-cyclododecanone205 (63) (both methyl groups are on the same side of the ring) in the solidstate yielded a single major product, as observed by GLC. This compound has beenidentified as the type I photoepimerization product by co-injecting the authentic sample(R*, R*)-2,12-cyclododecanone.205 (64) on GLC. However, the solution photoreactionof (R*, S*)-2,12-cyclododecanone (63) in hexane showed the formation of seven majorproducts (including the solid state product) on GLC; the, isolation and characterization ofthese products has yet to be achieved. The above experiment clearly suggests that the fateof the biradical intermediate in the solid state is dominated by rapid biradicalrecombination rather than by rearrangements to other type I products.Irradiation of diketone 31 (RT 11.3 mins) in the solid state for prolonged periodsresulted in the appearance of three new peaks in addition to that of 31a (RT 12.3 mins),on GLC at retention times of 10.8, 13.1 and 13.3 mins. After —60 hours of irradiation thefour products, along with the starting material, attained a photostationary state.Interestingly, irradiation of the photoproduct 31a also led to a similar product distribution.The photolysis of diketone 31 in cyclohexane also led to a photostationary state after —70hours of irradiation; however, the photoproduct corresponding to the peak at RT 13.3 minwas absent. The ratios of the photoproducts (%) at the photostationary state and theirretention times on GLC are given below.155Solid state irradiation of 31:RT's 10.8 (12 %), 11.3 (6 %), 12.3 (67 %), 13.1 (4 %), 13.3 (11 %).Solid state irradiation of 31a:RT's 10.8 (14 %), 11.3 (7 %), 12.3 (63 %), 13.1 (5 %), 13.3 (11 %).Irradiation of 31 in cyclohexane:RT's^10.8 (3 %), 11.3 (60 %), 12.3 (20 %), 13.1 (17 %).Apart from 31b, the new photoproducts observed could not be isolated from thefinal reaction mixture and characterized. Spectral analysis of the product mixtureindicated the absence of possible photoproducts from the type II reaction. In the solidstate reaction, as shown in Figure 77, at the photostationary state diketones 31 and 31amay coexist with their diastereomers 50, 51 and 52. The solution product 31b with aretention time of 13.1 min could therefore correspond to diketone 50, 51 or 52./50ct) i'20 ---=''-31^ 31a N^51Ct=IFZ=1-052Figure 77: A diagrammatic representation of possible diastereomers of tetramethylatedsixteen membered diketone (31), at the photostationary state.1565.1. The Photochemistry of Cyclic Mono - and Diketones in Zeolites.Generally, within a constrained or organized medium, both the photochemical andthe photophysical properties of organic molecules can be considerably modified.206,207 Inthis context, the internal structure of zeolites (pores and cages) has attracted recentattention.208 Zeolites are crystalline aluminosilicates with usually well-defuiedstructures.209,210 Therefore, they provide an ordered host environment for guestmolecules under investigation.The photochemistry of a large number of ketones adsorbed by a variety ofcommonly available zeolites has been reported in the literature,209,210 and shown toexhibit a wide variation in the product ratios compared to irradiation in isotropic media.The "zeolite method" was applied to the cyclic diketones prepared in our laboratory; andto cyclic monoketones prepared by Turro et al (Department of chemistry, ColumbiaUniversity, New York) in a collaborative study with V. Ramamurthy (Du Pont Company,Wilmington, DE). All photoreactions in zeolites were performed by Ramamurthy et a/.213The solution photochemical results of monoketones and diketones discussed in thischapter were performed in pentane and hexane respectively.The irradiation of ten (33), eleven (34), twelve (35), thirteen (36) and fifteen (38)membered cyclic monoketones and sixteen (9), eighteen (10) and twenty (11) memberedcyclic diketones included in cation (Li+, Na+, K+, Rb+, and Cs+) exchanged X and Yzeolites (faujasites) gave products derived from both type I and type II processes (Figure78). The major photoproducts obtained in the zeolites were type II cis and trans-cyclobutanols (66), cleavage product (67) and type I product alkenal (69). A plotrepresenting the type I to type II photoproduct ratios (type I / type II) in NaX zeolite withrespect to hexane (diketones) or pentane (monoketones) as solvent is shown in Figure 79.The type I to type II product ratios of compounds 10 and 36 included in various cation-exchanged zeolites are also shown in Figure 80 in the form of bar graph.HO HO^HO(CI-12^(CH2)n_2\■X65(^142)n-2xJ66c(ci_on_2xJ66f157hvType IType II142)n-^(^c H3\X67 monoketones:(33) X = CH2; n = 2.(34) X = CH2CH2; n = 2.(35) X = CH2; n = 3.(36) X = CH2CH2; n = 3.(37) X = CH2CH2; n = 4.H^(042)n^(C142)n+2y \x/cH268 69diketones:(9) X = CO; n = 5.(10) X = CO; n = 6.(11) X = CO; n = 7.Figure 78: The two modes of photoreaction of mono- and diketones in zeolites.1038 9 1 1158-a- Pentane/Hexane-a- NaY,33^34^35^365.0ruj 4.0m8. 3.0=a,94 2.0zza 1.01.-0.0ketone usedFigure 79: Enhancement of type I products in zeolite NaY with respect to the solutionreaction.ketone 10^ketone 36Figure 80: Dependence of type I to type II product ratios of compounds 10 and 36 oncations.The above results clearly indicate a dramatic enhancement of the type I processwithin zeolites. From Figure 79 it is apparent that, even though type I product formationis enhanced in every cation-exchanged zeolite, the extent of enhancement is higher withsmaller cations such as Li+ or Na+, but with the other cations the formation of type Iproduct is dramatically reduced. It is also necessary to direct our attention to the fact that159the ketone ring size dictates the extent of the enhancement of the type I products, and thatthe effect is greater when the ring is smaller.Variations in type I to type II product ratios have been reported for a variety ofacyclic ketones adsorbed on cation-exchanged X and Y zeolites.211-213 Theseinvestigations also reveal a significant influence of the cations on the selectivity of thephotochemical pathways.At this point, prior to analyzing the results, it may be helpful to give a briefdescription of the structure of zeolites. The primary building blocks of the zeolites are thefSiO414- and [A104]5- tetrahedra units. These units are linked at all corners to formchannels and cages or cavities (Figure 81) of distinct size, in such away that no twoaluminium atoms sharing the same oxygen atom.Primary cage structures (sodalite cages) are constructed with four and sixmembered rings of [SiO414- and [A10405- units. These sodalite cage units can construct"supercages" or "channels" in a number of ways (leading to different types of zeolites),two of which are illustrated in Figure 81. These cages and channels are generallyinterconnected and have access to exterior through a pore or window which cannot belarger than the channels or cages. The pore dimensions therefore determine the size of themolecule that can be absorbed into these structures. As a result of the difference in chargebetween the [SiO4]4- and [A104]5- units, the total framework charge of an aluminium-containing zeolite is negative and it is generally balanced by alkali or alkaline earth metalcations. The cations and water molecules present are located in the cages, cavities, andchannels of the zeolites. The position, size and number of cations, as well as the positionand number of water molecules, can significantly alter the properties of the zeolites.The X and Y zeolites, commonly known as "faujasite zeolites", used in theseexperiments have a 7.4 A pore size (diameter) with a supercage diameter of 12 A. Theinternal structure of these two zeolites is identical except for the difference in the ratio of160aluminium to silicon in the framework (the unit cell compositions of X and Y zeolites aregiven in Figure 81).Zeolite X & YX type M86(A102)86(Si02)106.264 H20Y type M56(A102)56(Si02)136.253 H20Figure 81: Illustration of the [SiO4]4- and [A104}5- tetrahedra that are the primarybuilding blocks of zeolites. Also shown are representations of the sodalitecage, zeolites (A, X and Y) and the unit cell compositions of X and Yzeolites.In the case of the large membered diketones, all rectangular conformations [3x3xJ,are narrow enough to enter the pore (7.4 A) regardless of the ring size, since the shortsegment of the conformation is only — 6.2 A in width. The largest molecule used in thisexperiment (twenty membered ring diketone) has a molecular length of 11.3 A, which canfit perfectly within the super cage (cage diameter --12 A). However, the rings larger thanthe twenty membered ring are too long to fit in the super cages,and therefore, could not beincluded. All molecules used for the investigation are expected to fit within a single cageof X and Y zeolites.161The supercage of X and Y zeolites contains cations located at three distinct sites asshown in Figure 82.214 The cations at location I are present within the socialite cage,while cations at locations II and III are within the supercages. Since the preferredpositions for the guest molecules are supercages, only the cations present within thesupercages are expected to influence the reactivity of the guest molecules. The cations atlocation II are present within the framework of the supercages, whereas the ones atlocation III occupy the void space of the supercages. Therefore the cations at location IIIare expected to influence the reactivity of the guest molecules both sterically andelectronically.SodaIle cage,^ 41 ITSager cage 11104P1mg IOWlipt-‘,41.40SPOFigure 82: Cation locations inside the faujasite cages.Turro and co-workers have undertalcen227,228 photochemical investigations ofseveral compounds related to the dibenzyl ketones included in zeolites, where cationswere found to have significant influence on the product distribution. In all of these cases,the variations in the product ratios were attributed solely to variations in the free volumeof the supercage with respect to the cation. Furthermore, a study by V. Ramamurthy et al.on benzoin alkyl ethers ,212 a-alkyldeoxybenzoins211a, and a-alkylbenzylketones212162included in zeolites also illustrated the importance of the size of the cations on the productdistribution.Apart from the steric effect, the electronic interaction of these cations on the guestmolecules is also known to play a major role in the product distribution in zeolites. Theinclusion of guest molecules on X and Y type zeolites has been widely investigated byseveral spectroscopic techniques.215 These studies indicates that if a molecule with ait-bond or polar functional group is adsorbed on zeolites, it interacts strongly with theexchangeable cations. The interaction energy depends on factors such as the type, radius(ionic) and charge density of the exchangeable cations, as well as the types of zeolites andthe structures of the adsorbed molecules. Singly charged cations, such as Li+ and Na+,show stronger interactions than the larger K+, Rb+,and Cs+ cations.Photochemical results similar to those observed for the cyclic ketones have beenreported211d for a series of a,a-dialkylphenyl ketones adsorbed on X and Y zeolites.Irradiations of these ketones in benzene and on zeolites (M+ = Li+, Na+, K+, Rb+ andCs) gave products from both type I and type II processes. It was also observed that thetype I process was enhanced significantly within zeolites compared to benzene photolysis.Furthermore, as observed for the cyclic ketones, Li+ and Na+ cations exerted a largerinfluence than other cations. The above results have been discussed on the basis of thechange in the binding ability of the cation with the carbonyl chromophore due to thevariation in the electrostatic potential of the cation.A similar argument has been suggested by Ramamurthy213 to explain the resultsobtained from cyclic mono- and diketones in zeolites. The cations present within thesupercage can interact electronically with the carbonyl chromophore and thus severelyimpede the hydrogen abstraction sterically (Figure 83). The photobehaviour of mono anddiketones can be influenced by zeolites, by altering the partitioning of the correspondingreactive intermediates 68 and 65 (Figure 84) between the reverse reaction to startingketone and decay to products.IH2 C,,,,.., , 1/NCH2H^H00It(66)type I-I.4--type II4.____x^X(68) (69)0..)^Fl......)HOx/ (65)X = CH2 monoketoneX = (C=0) diketone163H2c,I--.-----,--0,IFI2 C,. ••H tl)z.,........ ICH2H Hvx 1CH2 Type I00C=)Figure 83: Electronic interaction of lithium cation with the carbonyl chromophoreimpedes type II hydrogen abstraction sterically.Figure 84: Diagram illustrating the partitioning of the type 11 (65) and type I (68)biradical intermediates to products and to their starting ketones.164An increased rate of a-cleavage, a decreased rate of hydrogen atom abstractionand an increased rate of intramolecular hydrogen return of 65 should give rise to a greaterproportion of type I product, with the last of these being the least likely. Internalhydrogen return should not be favoured over cyclization and fragmentation of the type II1,4-biradica1,59,216 in a polar medium or a medium containing a large number of oxygens(capable of forming hydrogen bonds), as is the case within the zeolite cavity.217 Thissuggests that a reduction in the rate of the competing type II process is probably the maincause of the formation of type I products in zeolites.The well established218 fact that molecular motions are restricted within zeolitesindicates that reactions involving large segmental motions (type II cleavage) of thereacting molecule will be slowed inside zeolites. This has been supported experimentallyby the photochemical investigations of valerophenone (VP) and a,oc-dimethylvalerophenone (DMVP)219 in zeolites. The triplet lifetimes of these compoundsin various zeolites clearly indicate that the 'y-hydrogen abstraction process is considerablyrestricted when these ketones are adsorbed on zeolites.For medium and macrocyclic ketones, only a few of the several possibleconformational arrangements are suitable for y-hydrogen abstraction. In addition, stericand electronic influences imposed by the cations on guest molecules are expected torestrict conformational interconversions that would be favorable for y-hydrogenabstraction. Therefore, under such conditions, a slow type I process would be able tocompete with the type II process. Furthermore, the strong binding ability of Li+ and Na+cations to the carbonyl chromophore explains the comparatively large effect of thesecations.The photochemical study of cyclic ketones in zeolites establishes that type Iprocesses can in fact be induced even in systems that do not show any sign of suchreactivity in isotropic media. Such an investigation using zeolites provides an alternatestrategy to induce type I processes in cyclic mono- and diketone systems.165CHAPTER W6.0. General information.Melting points (mp): All melting points were taken on a Fisher-Johns hot stage meltingpoint apparatus and are uncorrected.Transition points (tp): Transition points were obtained from a differential scanningcalorimeter, a Mettler DSC-20 cell interfaced with a Mettler TC 10 TA processor and aSwiss Matrix printer/plotter. Samples (10-15 mg) weighed in an analytical balance wereplaced in a metal vial with a tiny hole and used for the experiment; the temperature wasincreased at a rate of 2 °C min- 1. The values reported for AH and temperature werestatistical averages of at least three runs.Infrared spectra (IR): The infrared spectra were recorded on a Perkin-Elmer 1710Fourier transform spectrometer. The positions of the absorption maxima are given incm-1. Spectra of oily compounds were obtained by placing them between two sodiumchloride pellets. Solid samples (2-5 mg) were ground with anhydrous KBr (100-200 mg)and pelleted using a Perkin-Elmer evacuated die 186-0002 and a Carver model Blaboratory press at 20,000 psi.Infrared (FTIR) studies of diketones at elevated temperatures: A special apparatuswith a KBr pellet-holder, made by the UBC Electrical Shop, was used for this purpose. AKBr pellet-holder was placed in the middle of an insulated metal coil and the desiredtemperatures were maintained inside the coil by passing an appropriate current through thecoil. The amount of current was controlled by a rheostat. The device was calibrated166before use by preparing a standard plot of the temperature inside the coil (measured by athermometer) versus the rheostat dial reading.Nuclear magnetic resonance spectra (nmr): Proton nuclear magnetic resonance(1H nmr) spectra were recorded in deuterated chloroform or benzene. The spectrometersused were: a Bruker AC-200 (200 MHz), Varian XL-300 (300 MHz), Bruker WP-400(400 MHz) and Bruker AMX-500 (500 MHz). Signal positions are reported in units of5, parts per million downfield from tetramethylsilane (TMS), which was used as aninternal standard. The number of protons, signal multiplicities, coupling constants (in Hz)and assignments are given in parentheses following the signal positions. The abbreviationsused to indicate the multiplicities of the proton signals are: s = singlet, br s = broad singlet,t = triplet, q = quartet and m = multiplet.Carbon nuclear magnetic resonance (13C nmr) spectra were recorded on BrukerAC-200 (50.3 MHz), Varian XL-300 (75.4 MHz), Bruker 400 (100.6 MHz) and a BrukerAMX-500 (125.8 MHz) spectrometers using deuterated chloroform or benzene as asolvent and an internal reference (TMS). Spectra signal positions are reported in parts permillion (5) relative to the standard, and the signals were assigned based in part on theattached proton test.22°Solid-state deuterium nmr studies and cross polarization magic angle spinning(CPMAS) experiments were recorded on a Bruker MSL-400 spectrometer.Ultraviolet spectra (UV): The UV spectra were recorded on a Perkin-Elmer Lambda-4Bspectrometer.Mass spectra (MS): Both low and high resolution mass spectra were recorded on aKratos MS50 mass spectrometer. A Karlo-Erba gas chromatograph coupled with a167Kratos MS80 mass spectrometer was used for GC-MS analysis. Relative intensities arerecorded as percentages of the most intense peak (base) and are given in parentheses.Microanalysis: Elemental analyses were performed by the departmental microanalyst,Mr. P. Borda. Samples were prepared as follows: Vials containing powdered samplewere placed in a special apparatus attached to a container with phosphorus pentoxide, andleft on the vacuum line (1-2 mmHg) for 24-48 hr prior to analysis, where the temperatureof the samples was maintained using refluxing solvents 15-50°C below their meltingpoints.Gas liquid chromatography (GLC): A Hewlett-Packard 5890A capillary gaschromatograph attached to a Hewlett-Packard 3392A integrator was used for all gaschromatographic analysis. Fused silica capillary columns (15 m x 0.25 mm) DB-1, DB-17and carbowax from J&W Scientific, Inc. were used with helium as a carrier gas. Columnhead pressure was maintained at 15 psi. All retention times reported have limits of±0.1 min.Thin layer chromatography (TLC): Aluminium sheets coated with 0.2 mm of silica gel(type 5554) from E.Merck were used for analytical work.Column Chromatography: For purification and separation purposes conventionalcolumn chromatography (gravity) and flash column chromatography221 were performedusing silica gel 60, 230-400 mesh (E.Merck) as the stationary phase. A mixture of ethylacetate and petroleum ether (35-60 °C) solvent system was used as an eluent for most ofthe compounds.High performance liquid chromatography (HPLC): A Waters 600E system controllerequipped with a Waters 486 UV detector and a Waters fraction collector was used. A168Radial-PAK cartridge Oa Porasil, particle size 104), with 8 mm (id) x 100 mm fromMillipore (cat # 85720) was used for analytical studies. For preparative scale work, asimilar column with an internal diameter of 25 mm (cat # 38504) was used.Crystallographic Analysis: All crystal structures were determined on a Rigaku 4-circlediffractometer by Dr. Steven J. Rettig and Prof. James Trotter of the UBC ChemistryDepartment.Powder diffraction patterns: Powder diffraction patterns of the 26-membered ringdiketone were recorded on an X-ray powder diffractometer which uses a Rigaku RotatingAnode X-ray (12 kw rotating anode).Solvents and reagents: Unless otherwise indicated, all reagents were purchased fromAldrich Chemical Co., and solvents were purchased from BDH Chemicals. Spectral gradesolvents were used for photochemical and spectroscopic studies. All diacids and diaciddichlorides were used as received. Valerophenone was purified by reduced pressuredistillation followed by recrystallization from pentane. Acetophenone was purified byreduced pressure distillation. Straight chain alkanes tetradecane, tricosane, docosane andtetracosane were purified by recrystallization and used as internal standards for gaschromatographic analysis.Dry solvents and reagents were prepared as follows:222 benzene, xylene anddimethoxyethane (DME) were distilled into a collecting reservoir by heating at reflux oversodium, under a dry nitrogen atmosphere. These solvents were transferred using an oven-dried syringe through a stopcock fitted on the reservoir. In some cases solvents weredistilled directly into the reaction vessel. Triethylamine was directly distilled and storedover calcium hydride. Deuterated chloroform and benzene used for spectral analysis werestored over Linde 4A molecular sieves.1696.1. Synthesis of Starting Materials.6.1.1. Synthesis of Diametric Diketones by Ozonolysis of Bicyclic Olefins.Cydodecane-1,6-dione (6) 108,109A solution of 1.5 mL (10 mmol) of 1,2,3,4,5,6,7,8-octahydronapthalene (17) in 40mL of 3:1 (v/v) MeOH:CH2C12 was placed in a three-necked 100 mL flask and cooled to-30°C in an acetone/dry ice bath. During ozonolysis, the temperature was graduallylowered to -60°C and ozone generated from Welsbach T-23 ozonator was bubbledthrough the solution. The reaction was monitored by thin layer chromatography (tic).Excess ozone was passed through the solution until the spot on the tic corresponding tothe starting material had completly disappeared. The solution was further flushed withoxygen for 10-15 min to remove any traces of ozone and 1.0 mL (13.6 mmol) ofdimethylsulphide was added through the middle neck of the flask. The solution wasstirred at -10°C for one hour, then at ice bath temperature for one hour and finally at roomtemperature for one hour. After the removal of solvent in vacuo, the remaining whiteresidue was diluted with water (10 mL) and extracted with diethyl ether (3 x 10 mL). Thecombined diethyl ether extracts were washed with water, dried over magnesium sulphateand evaporated to dryness to afford a white solid. A major peak found on GLC (DB17,120°C) at retention time (RT) 7.32 mins (62% by GLC) was later identified as the tenmembered ring diametric &ketone 6. Several fractional recrystallizations of the final crudesolid from ethyl acetate in petroleum ether solvent system yielded 1.32g (7.8 mmol, 78%)of pure diketone 6 as prisms with mp = 99-100°C(lit. °3 990C).1NMR: (C6D6, 200 MHz) 62.0-2.1 (8H, m, -CH2-00), 1.6-1.7 (8H, m, methylenes).13C NMR: (C6D6, 50 MHz) 6 207.4 (C=0), 37.4 (CH), 19.0 (CH2).IR (KBr): 2946, 1688 (C=0) cm-1.170MS m/e (rel. intensity): 168 (M+, 5), 150 (31), 111 (36), 97(36), 85(38), 84(56), 83(23),81(25), 68 (25), 67 (29), 57 (36), 56 (30), 55 (100), 43 (26), 41(44), 39 (21).Calculated mass: 168.1151, found: 168.1153.UV (Cyclohexane) Amax: 292 nm (e, 15) (n-e)The structure of diketone 6 was also determined by X-ray crystallographic analysis.Cyclododecane-1,7-dione (7)109,110Neutral aluminum oxide (6.5 g) from Fisher Scientific (Brockman activity 1) wasdried in the oven at 500 °C for 24 hours and carefully transferred to a 500 mL three-necked round bottom flask containing freshly cut sodium (30 mg) under dry nitrogen(obtained by successively passing the gas through a H2SO4 and then a CaSO4-KOH trap)conditions. The flask was placed in a sand bath and the temperature of the mixture wasgradually increased to 200 °C with stirring using a mechanical stirrer. At 200 °C,vigorous stirring was introduced for 20 min. Melted sodium diffused onto the aluminumoxide and formed a fine dark blue powder. After cooling to room temperature, a solutionof cyclododeca-1,5,9-triene (18) (7 mL, 38 mmol) in heptane (70 mL) was cautiouslyadded and the mixture was refluxed with stirring for 23 hr, until the GLC analysis (DB17,95 °C) showed that 85% of the starting material had been consumed. As reportedbefore,110 the final mixture showed five new peaks on GLC.Hydrogenation step :Refluxing was continued while bubbling hydrogen through the solution until thepeaks on the gas chromatogram were simplified into two main peaks with a ratio of 5:1.After 11 hr of reflux the catalyst was filtered off and washed with heptane.Ozonolysis step :The mixture from the hydrogenation step was subjected to an ozonolysisprocedure similar to the one used for diketone 6, with minor modifications, using 60 mLof Me0H, 20 mL of CH2C12 and 4 mL of (CH3)2S. The final mixture with two major171peaks on GLC (DB17, 90 °C) at retention times 11.65 and 16.47 min was subjected toflash-column chromatography (silica gel). Elution with 7% (v/v) ethyl acetate inpetroleum ether^(35-60°C) gave an oil (RT 11.65 min), a by-product. The peak atretention time^16.47 min was eluted with 9% (v/v) ethyl acetate in petroleum ether asa white crystalline solid (1.32 g, 6.7 mmol, 16.8%) and was later identified as the twelvemembered diametric diketone 7. Recrystallization of diketone 7 from the diethyl ether/petroleum ether solvent system gave needle and prism crystals with mp = 134-136°C(li110 mp = 133-135°C), the IR spectra of these two crystal modifications were found tobe identical.1H NMR: (C6D6, 300 MHz) 5 2.0 (8H, t, J = 7Hz, -CH2-00), 1.3 (8H, m, methylenes),1.0 (4H, m, methylenes).13C NMR: (C6D6, 75 MHz) 5 210 (C=0), 40 (CH2), 26 (CH2), 23 (CH2).IR (KBr): 2946, 1699 (C=0) cm-1-MS mie (rel.intensity): 196 (Mt, 1), 178 (7), 98 (37), 83 (37), 55 (100).Calculated mass: 196.1464, found :196.1472.UV (Cyclohexane) Xmax: 288 nm (e, 40) (n-R*)The structure of diketone 7 was confirmed by X-ray crystallographic analysis.6.1.2. Synthesis of Diametric Diketones by Blomquist's High DilutionTechnique.Diketones 8, 9, 10, 11, 12, 13 and 14 were prepared according to the procedure ofBlomquist et al.111 The following procedure described for the synthesis ofcyclotetradecane-1,8-dione (8) from suberic acid is typical.172Preparation of suberoyl chloride from suberic acid:Ten grams (53 mmol) of suberic acid and slightly more than two equivalents ofthionyl chloride (8.5 ml, 116 mmol) were placed in a 100 mL round bottom flask fittedwith a magnetic stirring bar and attached to a condenser with a nitrogen inlet. The flaskwas placed in a water bath and the stirred mixture was refluxed at 55°C until there was nofurther evolution of hydrogen chloride and sulfur dioxide (4-5 hr). After the reaction wascomplete, the excess thionyl chloride was removed by vacuum distillation. Trace amountsof thionyl chloride present in the crude acid chloride were removed by refluxing with3 x 15 mL portions of anhydrous diethyl ether for a few minutes followed by evaporatingthe ether in vacuo. A pale yellow crude acid chloride (11 mL) was obtained and used forthe following cyclization step.Cyclization step (high dilution technique) :The apparatus used in the cyclization step was a 5 litre three-necked roundbottomed flask, fittered with an all-glass mechanical stirrer through the central neck. A"Y" tube attached to the second neck had a vertical and an upwardly slanting side arm.An efficient condenser with a drying tube was connected at the upper end of the verticalarm and a nitrogen inlet was attached to the slanting side arm. A dropping funnel wasattached at the third neck.Three liters of benzene (freshly distilled over sodium) placed in the 5 litre roundbottomed (RB) flask were brought to a gentle reflux under nitrogen atmosphere and—500 mL of benzene was distilled off in order to ensure no residual moisture left inside theflask. Then 85 mL of triethylamine (freshly distilled over calcium hydride) was addedusing an oven dried syringe and then the mixture was brought to reflux.Crude acid chloride dissolved in 100 mL of benzene was added dropwise from anoven-dried funnel to the above stirred refluxing triethylamine-benzene solution over aperiod of three hours. After the addition was complete, heating was continued for an hour173and the mixture was stirred for another hour while cooling. The mixture was then filteredunder suction to remove the precipitated triethylamine hydrochloride. The filtrate wasfreed of excess triethylamine by washing with water (3 x 25 ml), and concentrated byremoving benzene as rapidly as possible in vacuo to yield a reddish-brown residue.Hydrolysis and decarboxylation  :The residue was transferred to a 250 mL round bottom flask to which wascarefully added with stirring a solution of potassium hydroxide, made by dissolvingpotassium hydroxide (10 g) in 50 mL of methanol. The resulting mixture was refluxed ona heating mantle for one hour, and after dilution with 50 mL of water, further refluxingwas continued for another two hours. The final reaction mixture was extracted withdiethyl ether (3 x 15 mL) and the combined ether extracts were dried over anhydrousmagnesium sulphate. After 1-2 hr, the solution was filtered and the solvent wasevaporated in vacuo. The final pale-brown colored residue on GLC (DB17, 200°C) gavetwo major peaks at retention times of 3.41 and 9.86 min which were later identified aspeaks corresponding to diketone 8 and a tricyclic y-pyrone 24 respectively. These twocompounds were isolated in pure form by flash column chromatography (silica gel, ethylacetate : petroleum ether = 3:97) , where the y-pyrone has a slightly longer retention timethan the diketone. Diketone 8 was eluted as a white crystalline solid (448 mg, 2 mmol,9.0 % yield). Recrystallization from diethyl ether/ petroleum ether gave plates with mp =148-149°C (HO 1 1 mp = 146.5-148°C). y-Pyrone 24 was also eluted as a white crystallinesolid (1.16 g, 5 mmol, 21% yield). Recrystallization of y-pyrone 24 from ethylacetate/petroleum ether gave prisms with mp = 108-109°C.Diketone (8)1H NMR: (CDC13, 300 MHz) 5 2.4 (8H, t, J = 7 Hz, -CH2-C=0), 1.6 (8H, m, methylenes),1.2 (8H, m, methylenes).17413C NMR: (CDC13, 125 MHz) ö 211.7 (C=0), 41.0, 27.0, 23.1.IR (KBr): 2923,1703 (C=0) cm.-1.MS mile (rel.intensity): 224 (Mt, 4), 206 (16), 167 (14), 139 (14), 125 (26), 113 (46), 112(100), 111 (38), 97 (40), 84(58), 69(39), 55 (75).Calculated mass: 224.1777, found: 224.1774.UV (Cyclohexane) )t.max: 283.8 nm (c, 41) (nit*)The structure of diketone 8 was confirmed by X-ray crystallographic analysis.2,3-5,8 bis(cycloheptano)-4-pyrone (24)111 NMR: (C6D6, 500 MHz) 5 2.60 (8H, m), 1.85 (4H, m), 1.72 (4H, m), 1.60 (4H, m).13C NMR: (C6D6, 125 MHz) 5 177.6 (C=0), 166.4 (0-C=C), 124.9 (0=C-C), 34.0 (CH2),31.8 (CH2), 26.2 (CH2), 24.9 (CH2), 22.4 (CH2).IR (KBr): 2925, 1657 (C=0), 1603 (C=C) cm-1.MS m/e (rel. intensity): 232 (M-I-, 21.1), 204 (33), 203 (23).Calculated mass: 232.1464, found: 232.1462.Anal. calcd for C15H2002: C, 77.55; H, 8.68. found: C, 77.50; H, 8.80.The structure of y-pyrone 24 was supported by X-ray crystallographic analysis.Cyclohexadecane-1,9-dione (9)The procedure used to prepare diketone 8 was modified by using azelaic acid(10 grams, 53 mmol) instead of suberic acid. A final pale-yellow residue showed a singlemajor peak on GLC (DB-17, 180°C) at a retention time of 8.05 min and which was lateridentified as the peak corresponding to diketone 9. The final mixture was subjected toflash column chromatography (silica gel) and elution with 4% ethyl acetate in petroleumether (35-60°C) yielded 1.9 g (7.4 mmol, 28% yield) of diketone 9 as a white solid.Recrystallization of diketone 9 from ethyl acetate/petroleum ether gave prisms with mp =85-86°C (lit103 mp = 83-85°C). Virgin crystals and the crystals annealed to 50°C175(3 cycles) were analyzed by differential scanning calorimetry and found to have anendothermic phase transition at 34°C^= 23 kJmo1-1) (lit103 transition point = 28°C).1H NMR: (CDC13, 300 MHz) 8 2.4 (8H, t, J = 7, -CH2-C=0), 1.7 (8H, m, methylenes),1.3 (12H, m, methylenes).13C NMR: (CDC13, 75 MHz) 8 212.4 (C=0), 41.9, 27.9, 27.6, 23.6.CPMAS 13C NMR: (100 MHz) 8 213.5 and 212.3 (2 C=0), 46.0 (CH2), 44.4 (CH2), 35.5(CH2), 29.4 (CH2), 22.8 (CH2).IR (KBr): 2979, 1703 (C=0) cm-1.MS mie (rel.intensity): 252 (Mt, 3), 98 (34), 83 (27), 55 (100), 43 (44), 41(66).Calculated mass: 252.2090, found: 252.2092.UV: (cyclohexane) Amax: 286 nm (e, 41) (nn*).The structure of diketone 9 was confirmed by X-ray crystallographic analysis.Cyclooctadecane-1,10-dione (10)Eighteen membered ring diametric diketone 10 was prepared from sebacic acid(15 g, 74 mmol) using the general procedure described for the synthesis of diketone 8.Most of the diketone 10 was precipitated out (with some impurities) from theconcentrated solution of the final mixture as a pale yellow mass(-90% by GLC - DB 1,200°C). Several fractional recrystallizations from ethyl acetate/petroleum ether gave purediketone as white prisms with mp = 95-97°C (lit223 mp = 96-97°C). The remainingdiketone in the final reaction mixture was purified by flash column chromatography (silicagel, ethyl acetate : petroleum ether (35-60°C) = 3:97) and the combined product totaled2.59 g (9 mmol, 25% yield).Virgin crystals and crystals that had been annealed at 90°C (3 cycles) wereanalyzed by differential scanning calorimetry and found to have an endothermic phasetransition at 86°C = 12 kJmol- 1) (lit103 transition point = 86°C)1761H NMR: (CDC13, 300 MHz) 5 2.4 (8H, t, J = 7 Hz, -CH2-C=0), 1.6 (8H, m, methylenes),1.3 (16H, m, methylenes)13C NMR: (CDC13, 75 MHz) 5 211.8 (C=0), 42.2 (CH2), 28.7 (CH2), 28.2 (CH2), 23.9(CH2).CPMAS 13C NMR: (100MHz) 5 220.5 (C=0), 52.6 (CH2), 40.9 (CH2), 39.3 (CH2), 35.4(CH2).IR (KBr): 2940, 1707 (C=0) cm-1.MS m/e (rel-intensity): 280 (Mt, 27), 223 (36), 183 (23), 112 (43), 111 (32), 98 (45), 97.(82), 95 (29), 85 (29), 83 (27), 82 (26), 81(41), 71(40), 69 (39), 67 (31), 58 (25), 57 (36),55 (100), 43 (42), 41(69).Calculated mass: 280.2403, found: 280.2401.UV: (cyclohexane) Xmax: 285 nm (c, 54) (n-e).Cydodocosane-1,12-dione (12)The procedure used for the preparation of diketone 8 was followed with only aslight modification by starting with the commercially available acid chloride dodecanedioyldichloride (4.7 ml, 19 mmol).The final mixture was analyzed by GLC (DB 17, 220°C) and subjected to flashcolumn chromatography (silica gel). Elution with 3% (v/v) ethyl acetate in petroleumether (35-60°C) yielded 1.3 g (4 mmol, 41% yield) of diketone 12 as a white crystallinesolid. Recrystallization from ethyl acetate/petroleum ether gave plates with mp = 54-55°C(lit223 mp = 54-55.5°C).1H NMR: (CDC13, 300 MHz) 5 2.4 (8H, t, J = 7 Hz,-CH2-C=0), 1.7 (8H, m, methylenes),1.3 (24H, m, methylenes)13C NMR:(CDC13, 75 MHz) 5 212.0 (C=0), 42.2 (CH2), 28.9 (CH2), 28.8 (CH2), 28.6(CH2), 23.8 (CH2).177CPMAS 13C NMR:(100Hz) 224 and 222.0 (2 C=0), 54.0, 48.7, 47.8, 45.0, 44.1, 42.9,42.4, 41.3, 39.8, 37.9, 37.2, 34.3, 33.4.MS m/e (rel.intensity): 336 (M-1-, 22), 211 (22), 168 (23), 153 (24), 135 (27), 125 (43), 111(30), 109 (27), 98 (26), 97 (31), 95 (41), 83 (34), 81(42), 71(39), 69 (69), 67 (38), 58 (28),57 (22), 55 (100), 43 (37), 41(69).Calculated mass: 336.3030, found: 336.3036.UV: (acetonitrile) A,max: 282 nm (E, 67) (n-e)The structure of diketonel2 was supported by X-ray crystallographic analysis.Cydotetracosane-1,13-dione (13)The procedure used to prepare diketone 8 was modified by using 10 g (41 mmol)of 1,11-undecanedicarboxylic acid. The final reaction mixture was analyzed by GLC(DB17, 250°C) and subjected to flash column chromatography (silica gel). Elution with3% (v/v) ethyl acetate in petroleum ether (35-60°C) yielded 1.34 g (4 mmol, 19%) ofdiketone 13 as a white solid and recrystallization from diethyl ether/petroleum ether gaveplates with mp = 62-63°C (Ho 14 mp = 62-63.5°C).1H NMR: (C6D6, 200 MHz) 5 2.1 (8H, t, J = 7 Hz, -CH2-C=0), 1.6 (8H, m, methylenes),1.2 (28H, s, methylenes).13C NMR: (CDC13, 75 MHz) 5 212 (C=0), 42.4 (CH2), 28.9 (CH2), 28.7 (CH2), 28.6(CH2), 23.9 (CH2).IR (KBr): 2913, 1706 (C=0) cm-1.MS mie (rel. intensity): 364 (M+,16), 98 (24), 97 (30), 95 (34), 83 (54), 81(40), 71(46), 69(59), 67 (40), 58 (39), 57 (44), 56 (22), 55 (100), 43 (90), 42 (25), 41(75).Calculated mass: 364.3343, found: 364.3344.UV: (Cyclohexane) Xmax : 285.5nm (e, 41) (n-e)The structure of diketone 13 was supported by X-ray crystallographic analysis.178Cyclohexacosane-1,14-dione (14)The procedure used for the preparation of diketone 8 was modified by using 10 g(39 mmol) of 1,12-dodecanedicarboxylic acid. The final mixture was analyzed by GLC(DB17, 260°C) and subjected to flash column chromatography (silica gel). Elution with3% (v/v) ethyl acetate in petroleum ether yielded 2.3 g (6 mmol, 29%) of diketone 14 as awhite crystalline solid. Careful recrystallization of diketone 14 from ethyl acetate/petroleum ether at room temperature for a prolonged period gave clear plates.Differential scanning calorimetry of the clear plates (virgin crystals) showed anendothermic phase transition OH = 6.3 kJmo1-1) at 54°C, but the annealed crystals (60°C,3 cycles) did not show any phase transition except the one at the melting point. Whenrecrystallization was carried out by seeding a concentrated solution with annealed crystals,needle-shaped crystals with a melting point identical to the plates (mp = 70° lit11469°C) were obtained. Agitation or sudden cooling of the saturated solution also led toneedle-shaped crystals. The differential scanning caloiimetry traces, FTIR spectroscopyspectra and the X-ray crystallographic analysis of the plates and the needle crystalmodifications confirmed them to be dimorphs.1H NMR: (CDC13, 500 MHz) 5 2.5 (8H, t, J = 7Hz, -CH2-C=0), 1.7 (8H, m, methylenes),1.4 (24H, m, methylenes).13C NMR: (CDC13, 125 MHz) 5 212 (C=0), 42.5 (CH2), 29.05 (CH2), 29.01 (CH2), 28.95(CH2), 28.90 (CH2), 28.76 (CH2), 28.70 (CH2), 23.8 (CH2).IR (KBr) (see Figure 60):plates: 2915, 2852, 1698 (C=0), 1471, 1414, 1374, 1214, 1198, 1172, 1004 cm-1.needles: 2919, 2848, 1704 (C=0), 1463, 1433, 1409, 1365, 1200, 1162 cm-1.MS m/e (rel.intensity): 392 (MI-, 13), 254 (23), 111 (22), 109 (21), 98 (23), 97 (43), 9695 (44), 83 (57), 71(49), 69 (59), 67 (30), 58 (32), 57 (32), 55 (100), 43 (39), 41(28).(24),Calculated mass: 392.3656, found: 392.3655.179UV (cyclohexane) Xmax : 274 nm (e, 88) (n-Tc*)6.1.3. Synthesis of Non-diametric Diketones by Blomquist's HighDilution Technique.Cyclohexadecane-1,8-dione (15)Synthesis of the non-diametric diketone 15 was achieved by using a mixture ofsuberic acid (9 g, 48 mmol) and sebacic acid (5 g, 23 mmol) and employing the sameprocedure described for the preparation of diketone 8. Repeated trials of the aboveprocedure using different ratios of the starting materials showed the above mentioned ratioto give the optimum yield of diketone 15.The final mixture according to GLC (DB17, 200°C) contained only 20% ofdiketone 15, due to the formation of the side products diketone 8, diketone 9 and they-pyrone 24. Diketone 9 and y-pyrone 24 were selectively removed from the the crudereaction mixture by several fractional recrystallisations to increase the proportion of thedesired product to 30%. Two elutions of this mixture through a silica gel column (ethylacetate:petroleum ether (35-60°C) = 3:97) afforded diketone 15 in 90% purity. Severalfurther fractional recrystallizations from diethyl ether/petroleum ether yielded purediketone 15 (318 mg, —1 mmol, 5.5%). Recrystallization from ethyl acetate/petroleumether gave plates with mp = 73-74°C.Both virgin and annealed (to 40°C and 60°C) crystals showed endothermic phasetransition points at 37°C (AG = 23 kJmo1-1) and 55°C (AG = 8 khno1-1) on the differentialscanning calorimeter.11-1 NMR: (CDC13, 300 MHz) 5 2.4 (8H, m, -CH2-C=0), 1.7 (8H, m, methylenes), 1.3(12H, m, methylenes).18013C NMR: (CDC13, 75 MHz) 8 212 (C=0), 42.2 (CH,), 41.4 (CH2), 27.9 (CH2), 27.5(CH2), 27.3 (CH2), 23.4 (CH2), 23.3 (CH2).IR (KBr): 2929, 1708 (C=0) cm-1.MS m/e (rel.intensity): 252 (M+, 14), 112 (31), 97 (37), 95 (20), 84(60), 83 (33), 71(25), 69(49), 67 (25), 58 (25), 57 (26), 56 (27), 55 (100), 43 (73), 42 (38).Calculated mass: 252.2089, found: 252.2090.Analysis calculated for C16H2802: C,76.14; H, 11.18. found: C, 76.30; H, 11.10.UV (cyclohexane) Xmax: 286 nm (e, 44) (nn*)The structure of diketonel5 was confirmed by X-ray crystallographic analysis.Cycloheptadecane-1,9-dione (16).Diketone 24 was synthesized by the procedure similar to that used for the synthesisof diketone 15, using a mixture of azeleic acid (5 g, 27 mmol) and sebacic acid (5.5 g,27 mmol). The final mixture on GLC (DB 17, 200°C) showed three major peakscorresponding to diketone 16 (50%), diketone 9 (24%), diketone 10 (13%) together withtraces of several minor peaks. Most of the side products 9 and 10 were selectivelyprecipitated from the crude reaction mixture and removed by filtration. The rest of themixture was subjected to conventional silica gel column chromatography, and elution with3% (v/v) ethyl acetate in petroleum ether (35-60°C) completely isolated a mixture ofdiketones 16 and 10 from the rest of the impurities. Further 3 separate chomatographicelutions of this mixture with 2% (v/v) ethyl acetate in petroleum ether gave diketone 16 in95% purity and which, on several recrystallizations from diethyl ether/petroleum ether,gave pure diketone 16 (253 mg, 3.5% yield). mp = 38-39°C.1H NMR: (CDC13, 400 MHz) 8 2.4 (8H, m, -CH2-C=0), 1.6 (8H, m, methylenes), 1.3(14H, m, methylenes).18113C NMR: (CDC13, 50 MHz) 5 217.5 (C=0), 42.45 (CH2), 41.94 (CH2), 28.26 (CH2),28.17 (CH2), 28.05 (CH2), 23.73 (CH2), 23.70 (CH,).IR (KBr): 2931, 1708 (C=0) cm-1.MS m/e (rel.intensity): 266^15), 111 (24), 98 (76), 84(21), 81(26), 71(28), 67(27), 57(26), 55 (100).Calculated mass: 266.2247, found: 266.2244.Anal. calcd for C17H3002: C,76.64; H,11.35. found: C, 76.50; H, 11.40.UV: (Cyclohexane) A,max: 285 nm (e, 48) (n-e)6.1.4. A Miscellaneous Reaction from Pimeloyl Chloride Under HighDilution Technique.1,2,3,4,5,6,7,8,-Octahydroxanthan-9-one (23):An attempt was made to synthesize the twelve membered ring diketone 7 from theappropriate diacid. However, the reaction afforded y-pyrone 23 as the only product.Pimelic acid (10 g, 62 rnmol) was used in a procedure similar to that used in the synthesisof diketone 8.Analysis of the final brown-colored crude reaction mixture on GLC (DB 17,185°C) showed a major peak at a retention time of 10.8 min with several other minorpeaks. The compound corresponding to the major peak was purified by flash-columnchromatography (silica gel) by eluting with 3.5% (v/v) ethyl acetate in petroleum ether(35-60°C). Recrystallization of the resulting white solid (3.5 g, 17 mmol, 56%) fromethyl acetate/petroleum ether gave compound 23 as prisms with mp 128-130°C (lit126mp = 131°C).1H NMR: (CDC13, 500 MHz) 5 2.45 (4H, t, -CH2-C-0), 2.35 (4H, t, J = 6.5 Hz, -CH2-C-C=0), 1.65 (4H, m, methylenes), 1.60 (4H, m, methylenes).18213C NMR: (CDC13, 100 MHz) 5 178.8 (C=0), 161.9 (C=C-0), 120.2 (C-C=0), 27.2(CH2), 21.7 (CH2), 21.4 (CH2), 20.6 (CH2).IR (KBr): 2934, 1662 (C=0), 1616 (C=C) cm-1.MS m/e (rel.intensity): 204 (M+, 68), 203 (100), 189 (29).Calculated mass: 204.1151, found: 204.1144.Analysis calculated for C13H1602: C, 76.44; H, 7.90, found: C, 76.51; H, 7.97.The structure of compound 23 was supported by X-ray crystallographic analysis.6.1.5. Synthesis of Diametric Diketone by Dieckmann CondensationReaction.Cycloeicosane-1,11-dione (11)112The synthesis of the twenty membered ring diketone 11 was carried out via aDieckmann condensation reaction under high dilution conditions with high speed stirring.The apparatus used was similar to the one described for the synthesis of diketone 8 withthe exception that instead of a "Y" tube, a cyclic "high dilution apparatus" equipped with asyringe pump (Sage Instruments, model 341A) and an efficient reflux condenser wasattached to the second neck. Dry nitrogen was bubbled through the solution via the thirdneck of the three-necked RB flask.A 60 mL solution of diethyl dodecanedioate (9 g, 30 mmol) in xylene (freshlydistilled over Na) was slowly added over a period of 24 hrs (2.5 mL hr-1) from a syringepump into a refluxing stirred solution of potassium tert-butoxide(24 g, 62 mmol) and dryxylene (1000 mL). Vigorous stirring was maintained throughout the reaction. After all ofthe ester had been added, stirring and refluxing was continued for one hour and thereaction mixture was allowed to cool to room temperature.183The mixture was then acidified with glacial acetic acid, washed with water(3 x 25 mL) and filtered to remove insoluble polymeric ketones. A reddish-brown residueobtained following the evaporation of the solvent in vacuo was placed in a 100 mL RBflask fitted with a reflux condenser and 15 mL of 3N hydrochloric acid was cautiouslyadded with stirring; a small amount of absolute ethanol (3 mL) was also added to promotethe solubility. The mixture was refluxed on the heating mantle for 5 hr and cooled toroom temperature. The acidic mixture was extracted with ether (3 x 10 mL) and thecombined ether extracts were washed with 10% NaHCO3 (3 x 15 mL), dried overmagnesium sulphate, filtered and evaporated to dryness in vacuo.Gas chromatographic analysis (DB17, 220°C) of the final mixture showed a majorpeak corresponding to the diketone 11 at a retention time of 10.83 min with several minorpeaks. Purification by flash column chromatography (silica gel, ethyl acetate : petroleumether (35-60°C) - 3:97) afforded a colourless solid (647 mg, 2.1 mmol, 14%) withmp = 54°C (lit103 mp = 54°C). Recrystallization from ethyl acetate/petroleum ethersolvent system gave plates.1-H NMR: (CDC13, 300 MHz) 5 2.4 (8H, t, J = 7 Hz, -CH2-C=0), 1.4 (8H, m, methylenes),1.2 (20H, m, methylenes).13C NMR: (CDC13, 75 MHz) 8 212.0 (C=0), 42.2 (CH2), 28.5 (CH2), 28.3 (CH2), 23.7(CH2).IR (KBr): 2924, 1699 (C=0) cm-1.MS m/e (rel.intensity): 308 (Mt, 57), 251 (37), 212 (24), 197 (30), 155 (27), 154 (40), 139121 (21), 111 (62), 98(31), 81(36), 71(40), 69 (71), 67(32), 58(29), 55 (100), 41(81).Calculated mass: 308.2717, found: 308.2722.UV: (cyclohexane) Xmax: 281 (e, 53) (n-e)The structure of diketone 11 was confirmed by X-ray crystallographic analysis.(34),1846.1.6. Synthesis of Cyclic Keto-alcohols by Partial Reduction ofDiketones.9-Hydroxycyclohexadecanone (29):127A solution of sodium borohydride (95 mg, 2.5 mmol) in absolute ethanol (30 mL)was slowly added from a dropping funnel to a stirred solution (70 mL) ofcyclohexadecane-1,9-dione 9 (2.52 g, 10 mmol) in absolute ethanol (70 mL) at roomtemperature. The reaction was followed by GLC (DB 17, 170°C) analysis using 0.1 mLaliquots taken from the reaction mixture at different time intervals (samples werequenched with water and ether extracts were injected on GLC).As the amount of keto-alcohol started to decrease, addition was stopped and themixture was quenched with water and extracted with diethyl ether (3 x 15 mL). Thecombined ether extracts were dried over anhydrous magnesium sulphate, filtered andevaporated to dryness in vacuo. Analysis of the final mixture on GLC showed 3 majorpeaks at retention times 5.89, 6.47 and 7.20 min, corresponding to the unreacted diketone9, kern-alcohol 29, and cyclohexadecane-1,9-diol 30 (both cis and trans) respectively.Both products were separated from the unreacted starting material in pure form byconventional column chromatography (silica gel). The polarity of the solvent wasgradually increased from 2% to 5% (v/v) ethyl acetate in petroleum ether (35-60°C).Unreacted starting material was eluted with 3% solvent, followed by the keto-alcohol 29as a white crystalline solid (940 mg, 3.7 mmol, 37%) and the diol 67 (mixture of both cisand trans) as a white solid (204 mg, 8%) with mp = 107-109°C. Recrystallization of keto-alcohol 29 from hexane gave needle-shaped crystals with mp = 73-74°C.9-Hydroxy cydohexadecanone (29)1H NMR:(C6D6, 300 MHz) 8 3.5 (1H, m, -CH-OH), 2.0(4H, m, methylenes), 1.1-1.5 (24H,m, methylenes).18513C NMR: (C6D6, 75 MHz) 6 209.8 (C=0), 70.0 (=CH-OH), 41.9 (CH2), 35.1 (CH2),27.8 (CH2), 27.6 (CH2), 27.5 (CH2), 23.5 (CH2), 23.2 (CH2).IR (KBr): 3400-3100 (OH), 2930, 1704 (C=0) cm-1.MS m/e (rel.intensity) 254 (M+, 11), 236 (51), 211 (27), 183 (31), 155 (38), 142 (44), 127(64), 111 (36), 98(48), 83(61), 71(62), 57(84), 55 (100), 43 (87), 41(87).Calculated mass: 254.2247, found: 254.2243.Anal. calcd for C16H3002: C, 75.40; H, 12.00. found:C, 75.54; H, 11.89.UV: (cyclohexane) Xmax: 275nm (e, 46) (n-e).Cyclohexadecane-1,9-diol (67) (cis and trans)1H NMR: (CDC13, 300 MHz) 5 3.75 (2H, m, -CH-OH), 1.5 (8H, t, J = 6.5 Hz, methylenes),1.4 (20H, m, methylenes).13C NMR: (CDC13, 75 MHz) 8 70.6 (=CH-OH), 35.0 (CH,), 27.1 (CH2), 27.0 (CH2), 26.9(CH2), 26.8 (CH2), 23.2 (CH2), 22.8 (CH2).IR (KBr): 3500-3100 (OH), 2933 cm-1.DCI MS m/e (rel.intensity): 274 (M++1+NH3, 31), 257 (M++1, 85), 221 (M++1-2H20,100).Calculated mass: 256.2404, found: 256.2394.Anal. calcd for C16H3002: C, 74.94; H, 12.58. found: C, 75.13; H, 12.65.10-Hydroxy cyclooctadecanone (30)The procedure used for the preparation of keto-alcohol 29 was modified by usingcyclooctadecane-1,10-dione (10) (2.24, 8 mmol) and almost three times the stoichiomenicamount of sodium borohydride (228 mg, 6 mmol) used for the synthesis of keto-alcohol29. Analysis of the final mixture on GLC (DB17, 180°C) showed three major peaks asobserved in the synthesis of keto-alcohol 29. Purification by conventional columnchromatography (silica gel, ethyl acetate:petrolium ether (35-60°C)- 2:98 to 6:94) gave186keto-alcohol 30 as a white solid (587 mg, 2.1 mmol, 26% yield) plus a white crystallineby-product, cyclooctadecane-1,10-diol 68 (772 mg, 2.7 mmol, 34% yield).Recrystallization of keto-alcohol from hexane gave plates with mp = 78-79°C.Recrystallization of diol 68 from pure CHC13 gave needles with mp = 118-120°C.The second crop of crystals grown from the mother liquor gave flakes with mp = 133-134°C. Infra red spectra of these two crystal modifications show some dissimilarities inthe fingerprint region. X-ray crystallographic analysis of the needles revealed that bothhydroxy groups are on the same side of the ring (cis). The morphology of these twobatches of crystals were independent of the solvent of recrystallization. This suggests thatthese two crystal modifications could be stereoisomers and not dimorphs.10-Hydroxy cyclohexadecanone (30)1H NMR: (C6D6, 300 MHz) 5 3.6 (1H, m, -CH-OH), 2.0 (4H, m, methylenes), 1.2-1.6(28 H, m, methylenes).13C NMR: (C6D6, 75 MHz) 5 210.0 (C=0), 69.1(=fH-OH), 41.9, 36.0, 28.2, 27.6,24.5, 23.7.IR (KBr): 3575-3475(OH), 2927, 1708 (C=0) cm-1.MS m/e (rel.intensity): 282 (Mt, 2), 264 (26), 141 (39), 109 (26), 108 (28), 98 (27), 97 (37),96 (43), 95 (44), 83 (39), 82 (34), 81(63), 71(41), 69 (45), 67 (55), 55 (100), 43 (33), 41(79).Calculated mass: 282.2560, found: 282.2556.Analysis calculated for C18E13402: C,76.54; H,12.13, found: C, 76.49; H, 12.17.UV (cyclohexane) Xmax: 283 nm (n-e).Cyclooctadecane-1,10-diole (68)1H NMR: (CDC13, 300 MHz) 5 3.6 (2H, m, -CH-OH), 1.5 (8H, m, methylenes), .1.3(24H, bs, methylenes).18713C NMR: (CDC13, 75 MHz) 5 70.7 (=CH-OH), 35.3, 27.7, 27.4, 23.6.IR (1(13r):needle: 3500-3200 (OH), 2931, 1461, 1436, 1301, 1103, 1015, 998, 978 cm-1.plates:^3500-3200 (OH), 2925, 1460, 1338, 1157, 1047, 1018, 995, 978cm-1.DCI MS m/e (rel.intensity): 302 (M++1+NH3, 44), 285 (M++1, 100), 249 (M++1-2H20,72).Analysis calculated for C1 8H3602: C, 76.00; H, 12.75, found: C, 75.96; H, 12.82.6.1.7. Sythesis of Tetramethylated Di ketones.Tetramethy1cyc1ohexadecane-1,9-dione-(2R*,8S*,10R*,16S*) (31)128A three-necked 200 mL round bottom flask containing 1.9 gams (48 mmol) ofpotassium hydride (purified under nitrogen from 22.4% (w/w) potassium hydride inmineral oil using anhydrous ether) and 80 mL of dimethoxy ethane (DME) (freshlydistilled over sodium) was kept in an ice bath and to this, a 50 mL solution ofcyclohexadecane-1,9-dione (9) in DME was slowly added with stirring under nitrogen.To the resulting suspension 2 mL of methyl iodide (purified by passing through a columnof basic alurnia) was added dropwise with continuous stirring and cooling. After themixture had been stirred for 15 min, it was filtered and the residual potassium hydride waswashed with ether. The filtrate was then washed with water (3 x 15 mL), dried overmagnesium sulphate and rotatory evaporated to give a white solid. The final mixture onGLC (DB17, 190 °C) showed three major peaks with five other minor peaks.Recrystallization from ethyl acetate/petroleum ether solvent system enabled the selectivecrystallization of two of the three major compounds in an almost 1:1 ratio. According toGC-MS analysis, both have parent masses corresponding to the tetramethylated diketone31.188Purification by HPLC (preparative column, ethyl acetate:hexane = 5:95, flow rate= 5 ml min-1) yielded 431 mg (1.4 mmol, 15% yield) of diketone 31 as a white solid.Recrystallization from diethyl ether/petroleum ether solvent system gave needles with mp= 120 °C. The stereochemistry of diketone 31, was confirmed by X-ray crystallographicanalysis.1H NMR: (C6D6, 400 MHz) 8 2.4 (4H, m, =CH-C=0), 1.7 (4H, m), 1.1 (16H, m,methylenes), 1.0 (12H, d, J = 6.5, methyls).13C NMR: (C6D6, 50 MHz) 8 215 (C=0), 44.6 (CH2), 32.5 (CH2), 29.5 (CH2), 26.9(CH2), 16.7 (-CH3).IR (KBr): 2929, 1700 (C=0) cm-1.MS m/e (rel.intensity): 308 (M+, 28), 223 (30), 154 (30), 125 (30), 112 (70), 97 (49), 86(91), 83 (40), 81(24), 71(42), 69 (82), 57 (63), 56 (44), 55 (100), 43 (75), 41(83).Calculated mass: 308.2717, found: 308.2722.Analysis calculated for C20143602: C, 77.86; H, 11.76. found: C, 77.59; H, 11.67.UV (cyclohexane) Amax: 282 nm (e, 56) (n-Tc*)Tetramethylcyclotetracosane-1,13-dione-(2R*,12S*,14R*,24S*) (32)128The procedure used for the preparation of diketone 31 was applied to 1.5 g(4 mmol) of cyclotetracosane-1,13-dione 13. The final mixture on GLC (DB 17, 240°C)showed three major peaks. Recrystallization of the final mixture from ethylacetate/petroleum ether enabled the selective crystallization of diketone 32 along with animpurity (12% by GLC). Purification of diketone 32 by HPLC (preparative column, ethylacetate : hexane=2:98, flow rate = 5 ml min-1) yielded 336 mg (0.8 mmol, 21% yield) ofwhite solid. Recrystallization of diketone 32 from ethyl acetate/petroleum ether gaveneedles with mp = 106-107°C. The stereochemistry of diketone 32 was confirmed byX-ray crystallographic analysis.1891H NMR: (C6D6, 300 MHz) 5 2.4 (4H, m, =CH-C=0), 1.8 (4H, m), 1.2 (32H, bs,methylenes), 1.0 (12H, d, J = 6.5, methyls).13C NMR: (C6D6, 75 MHz) 5 216 (C=0), 45.1 (=H-CH3), 33.2 (CH2), 30.3 (CH2), 30.2(CH2), 27.6 (CH2), 17.1 (-CH3).IR (KBr): 2919, 1699 (C=0) cm4.MS m/e (rel.intensity): 420 (Mt, 83), 336 (25), 335 (100), 97 (47), 86 (99), 83 (54), 71(33),69 (85), 57 (50), 56 33), 55 (99.5), 43 (50), 41(48).Calculated mass: 420.3969, found: 420.3967.Analysis calculated for C28115202: C, 79.94; H, 12.46. found: C, 80.37; H, 12.65.UV (Cyclohexane) Xmax: 282 nm (e, 54) (n-it*)6.1.8. Deuteration of Diketones.Cyclohexadecane-1,9-dione-2,2,8,8,10,10,16,16-d8 (69)To a stirred refluxing solution of cyclohexadecane-1,9-dione 9 (1 g, 3.97 mmol)and 25 mL of Me0D, 6.0 mL of a suspension of MeOK in Me0D (potassium hydroxidepellets were added to Me0D until the solution turned turbid) was added along with 50 mLof D20. After refluxing for two hours, the reaction mixture was cooled to roomtemperature, neutralized with conc HC1, diluted with water (10 mL) and then extractedwith diethyl ether (3 x 10 mL). The combined ether extracts were dried over anhydrousmagnesium sulphate and evaporated to dryness to yield 99 mg (3.8 mmol, 96% yield) ofdiketone 69. Recrystallization from ethyl acetate/petroleum ether gave plates with mp =86°C.1H NMR: (CDC13, 300 MHz) 5 1.6 (8H, m, methylenes), 1.2 (12H, br s, methylenes).13C NMR: (CDC13, 75 MHz) 6 212.6 (C=0), 27.9 (CH2), 27.6 (CH2), 23.4 (CH2).190MS m/e (rel.intensity) 260 (Mt, 26), 131 (32), 130 (43), 129 (28), 101 (42), 100 (100),85 (59), 69 (29), 57 (40), 56 (34), 45 (32).Cyclooctadecane-1,10-dione-2,2,9,9,11,11,18,18-4 (70)The procedure used for the preparation of deuterated diketone 20 was applied tothe eighteen membered ring dilcetone 10 (560 mg, 2 mmol). Recrystallization of thedeuterated diketone 70 from ethyl acetate/petroleum ether gave plates (530 mg, 1.84mmol, 92%) with mp = 96-97°C.1H NMR: (CDC13, 300 MHz) 8 1.6 (8H, m, methylenes), 1.3 (16H, br s, methylenes).13C NMR: (CDC13, 75 MHz) 8 212.4 (C=0), 28.7 (CH2), 28.1 (CH2), 23.6 (CH2).MS ink (rel.intensity): 288 (Mt, 51), 227 (49), 189 (29), 145 (38), 144 (55), 127 (62),126 (36), 114 (68), 99 (100), 87 (32), 84 (29), 83 (39), 82 (27).Cyclohexacosane-1,14-dione-2,2,13,13,15,15,26,26418 (71)The procedure used for the preparation of diketone 69 was applied to twenty-sixmembered ring diketone 14 (1 g, 2.55 mmol). Recrystallization of diketone 71 from ethylacetate/petroleum ether gave both plates and needles (756 mg, 1.89 mmol, 74% yield)with mp = 67-68°C.1H NMR: (CDC13, 200 MHz) 8 1.2 (8H, m, methylenes), 1.0 (32H, br s, methylenes).13C NMR: (CDC13, 50 MHz) 8 28.9 (CH2), 23.6 (CH2).MS tn/e (rel.intensity): 400 (Mt, 4), 392 (14), 254 (27),114 (26), 111 (39), 109 (37), 98 (45), 97 (70), 95 (64), 85196(53),(28), 181 (26), 12583 (72), 81(58).(42),1916.2. Photochemical studies.6.2.1. General.Photochemical reactions of diketones were explored in solution and in the solidstate. All reactions were performed with the Pyrex-filtered output (A, > 290 nm) of a450 W medium pressure Hanovia lamp, placed in a water-cooled Pyrex immersion well.Irradiations were carried out at various temperatures, especially in the case of diketoneswith transition points; the solid state reactions were conducted above and below thetransition points. All solution phase reactions were performed in reagent grade hexane,with the exception of diketone 10, where octane was used as solvent at 90°C.Photoproduct ratios measured for the two different solvents at room temperature suggestsno apparent solvent effects.Analytical photolysis  (general procedure):Solution and solid state photolyses were conducted using a minimum of threesamples, and for each sample, irradiations for different lengths of time were explored.Aliquots were routinely injected on GLC at different time intervals and the peak arearatios of the major photoproducts were noted. For each analysis at least three sampleinjections were made and the statistical average of the photoproduct ratios were recorded.Finally the detector response for each photoproducts was calculated to obtain the actualproduct ratios. Total percent conversion to products was limited between 10-15 % toprevent the formation of secondary photoproducts, and especially in solid state reactionsto prevent the effect of sample melting on product ratios. The reported product ratios(Table 1V) correspond to 0% conversion to products, which were obtained fromextrapolating the product ratios versus percentage conversion plots to 0% conversion.Analytical photolyses performed at 20 °C and above were carried out using theapparatus shown in Figure 86. Two specially designed Pyrex test tubes containing the192solution (15-20 mg m1-1) of the compound under investigation were placed inside a Pyrexrefluxing apparatus.condensorFigure 86: Apparatus used for the analytical reactions at elevated temperatures.The desired temperatures were maintained by refluxing appropriate solvents orazeotropic mixtures. The solvent or the solvent system used and their correspondingboiling points are given in Table XVII.Table XVII: Solvent systems and their corresponding boiling points.SOLVENT / SOLVENT SYSTEM BOILING POINTdichloromethane —40°Cacetone : hexane = 59:41 50°Cchloroform —60°Ccyclohexane —80°CIsobutylalcohol : water = 70:30 90°C193Irradiations below 20°C were carried out by using a bath (ethanol in a Pyrexcontainer) controlled by a Cryocool CC-100-II immersion cooling system from NeslabInstruments, Inc. and the temperature was maintained within ±2 °C.Solid state reactions:Approximately 5 mg of the compound under investigation was dissolved in— 0.5 mL of diethyl ether and a thin film was carefully formed on the inner surface of a testtube (10 mL) by slow solvent evaporation. Any remaining traces of solvent were removedunder vacuum and the test tube was sealed with parafilm film after the air was exchangedby nitrogen. Irradiations of single crystals and powdered crystals were also investigated inorder to compare the results, but no significant differences in product ratios wereobserved.Solution reaction:A 10-1 M solution of the compound (1.0 mL) under investigation in a pyrexphotolysis tube (3 mm) was degassed by freeze-pump-thaw cycles (at least three times)and sealed under nitrogen atmosphere prior to the photolysis. All irradiations wereperformed at a constant distance (12") from the lamp.Preparation and photolysis of annealed crystals:Diketones that exhibit solid-solid phase transitions were photolyzed above andbelow the transition points. Crystals annealed above the transition points were alsoirradiated at room temperature. Temperatures were gradually raised 5-15°C above thetransition point (but below the melting point) on the hot stage of the Fisher-Johns meltingpoint apparatus and slowly cooled to room temperature. Usually this cycle was repeatedat least three times prior to irradiation. Usually the transparent crystal cracked whilepassing through the transition point and finally became opaque. Irradiations of powderedannealed crystals were also performed.194Preparative scale photolysis (General procedure) :For solid state photolysis, powdered crystals (0.5 - 1.0 g) were sandwichedbetween Pyrex glass plates (2.5" x 1.0"), and the edges of these plates were taped with3M magic tape (Scotch 810). Taped plates were then sealed in polyethylene bags filledwith N2 and photolyzed. During irradiation the reaction progress was monitored by GLC(DB 17 or DB 1) and the total percentage conversion to products generally maintainedbetween 10% and 15%. After the reaction had been stopped, the final mixture wasscraped off the plates and the photoproducts were purified by column chromatographyand recrystallization techniques. The fractions collected from the column were analyzedby either thin layer chromatography or by GLC and the appropriate fractions werecombined and the solvent was removed in vacuo. Photoproducts were then characterizedby spectral and X-ray crystallographic analysis.Unless otherwise indicated, for the cyclobutanol photoproducts, the stereochemistry at the ring junction was determined by comparing the spectral characteristicswith those of the photoproducts (9c and 11t) and with known stereochemistry determinedby X-ray, based mainly on the chemical shift of the methine carbon (Table III).6.2.2. Photochemistry of Diametric Diketones.The following procedure described for cyclododecane-1,7-dione 7 is typical for apreparative scale solution reaction.A 250 mL solution of diketone 7 (750 mg, 3.8 mmol) in reagent grade hexane wasplaced in a water-cooled Pyrex immersion well setup and deoxygenated by bubblingnitrogen through the stirred solution for 1/2 hr. A steady flow of nitrogen and stirring wasmaintained throughout the irradiation. The progress of the reaction was analyzed at195different intervals by GLC (DB 17, 155°C). Three new major peaks were observed onGLC at RT's 1.58, 3.27 and 7.94 min. Reaction was stopped when the total conversion toproducts was 15%. The white semisolid mixture obtained after evaporating the solvent invacuo, was subjected to column chromatography (silica gel, Et0Ac:petroleum ether (35-60°C) = 5:95 to 9:91). The polarity of the solvent was gradually increased from 5% to9% (v/v) Et0Ac in petroleum ether.The compounds at 1.58 and 3.27 min on GLC were eluted together as a mixturewith 8% (v/v) Et0Ac in petroleum ether. The third product at RT 7.94 min was elutedwith 9% (v/v) Et0Ac in petroleum ether as an oil (45 mg, 6% yield) and was lateridentified as Bicyclo[8.2.0]dodecan-4-one, 10-hydroxy-(1R*,10R*)-(±) (7c)The compounds at 1.58 and 3.27 min were purified by HPLC (preparative column,Et0Ac:hexane = 15:85, flow rate = 5 mL min-1). Compounds 7u (oil, 32 mg, 4% yield)and 7e (white solid, 94% pure by GLC) respectively were obtained. Severalrecrystallizations of 7e from Et20/petroleum ether gave pure 7e as flakes (23 mg, 3%yield) with mp = 37-38°C. Compound 7e was later characterized as 11-dodecene-2,8-dione. According to spectral analysis, 7u appeared to be a mixture of compounds. Severalattempts at purification were unsuccessful. Due to the complexity of the spectra, thecompounds in the mixture could not be characterized. The product ratio at 0%conversion is given in table III.11-Dodecene-2,8-dione (7e)1H NMR: (C6D6, 300 MHz) 8 5.8-5.6 (1H, m, vinylic), 4.9 (2H, m, vinylic), 2.2 (2H,two overlapping triplets, -CH2-CH=CH2), 2.0 (2H, t, J=7 Hz, CH2-C=0), 1.9 (4H, t, J=7Hz, -CH2-C=0), 1.7 (3H, s, methyl), 1.5-1.3 (4H, m, methylenes), 1.1-1.0 (2H, m,methylene).19613C NMR: (C6D6, 100 MHz) 8 207.7 and 206.2 (2C=0), 137.7 (-CH=CH2), 115.0 (-CH=CH2), 43.1 (CH2), 42.2 (CH2), 41.6 (CH2), 29.3 (-CH3), 28.9 (CH2), 23.6 (CH2),23.4 (CH2).IR (KBr): 3082, 2934, 1704 (C=0) cm-1.MS: m/e (rel.intensity) 196 (Mt, 0.5), 95 (52), 83 (31), 55 (76), 43 (100).Calculated mass: 196.1464, found: 196.1460.Anal. calcd. for C12H2002: C, 73.43; H, 10.27. found: C, 73.45; H, 10.36.Bicyclo[8.2.0]dodecan-4 -one, 10-hydroxy- (1R*,10R*) - (±) (7c)13C NMR: (C6D6, 50 MHz) 8 214.2 (CO), 78.5 (C-OH), 48.6 (methine carbon), 43.3(CH2), 36.9 (CH2), 36.0 (CH2), 33.7 (CH2), 27.4 (CH2), 24.7 (CH2), 23.4 (CH2), 21.1(CH2), 17.0 (CH2).IR (neat): 3600-3200 (OH), 2970, 1702 (C=0) cm4.MS: mie (rel.intensity) 196 (Mt, 5), 178 (50), 168 (15), 150 (35), 149 (67), 135 (64),125 (29), 121 (35), 111 (40), 109 (29), 108 (31), 107 (57).Calculated mass: 196.1464, found: 196.1467.Solid state photolysis of diketone 7An analytical solid state reaction was carried out as described in the generalexperimental section. A major peak at RT 7.94 min with traces of peaks at 1.58 and3.30 mm on GLC (DB 17, 155°C) were observed.A preparative scale solid state reaction was not performed and the major productwas not isolated, but the peaks at RT 7.94 and 3.27 min were assumed to be compounds7c and 7e isolated in the solution state reaction, based on co-injection experiment on GLC.197Photolysis of Cyclotetradecane-1,8-dione (8):Irradiation of dilcetone 8, both in solution and in the solid state, showed threemajor new peaks on GLC (DB 17, 160°C) at RT's 6.04, 11.79 and 12.91 min. Preparativescale solid state reaction was carried out with 950 mg of starting material as described inthe general procedure. Photolysis was stopped after 16% of the starting material had beenreacted.All three photoproducts were purified by silica gel column chromatography(Et0Ac:petroleum ether (35-60°C) = 4:96 to 10:90) and were later identified byspectroscopic analysis. 13-tetradecene-2,9-dione (8e) (RT 6.04 min) was eluted with4% (v/v) Et0Ac in petroleum ether as a white solid (19 mg, 2% yield). Recrystallizationof 8e from Et20/petroleum ether gave flakes with mp = 43-44°C. A trans-cyclobutanol,bicyclo[10.2.0]tetradecan-5-one,12-hydroxy-(1R*,12S*)-(±) (8t) (RT 11.79 min) waseluted as an oil with 9% (v/v) Et0Ac in pet-ether (38 mg, 4%). A cis-cyclobutanol,bicyclo[10.2.0]tetradecan-5-one,12-hydroxy-(1R*,12R*)-(±) (8c) (RT 12.91 min) waseluted as an oil with 10% (v/v) Et0Ac in petroleum ether (86 mg, 9%).13-tetradecene-2,9-dione (8e)1H NMR: (C6D6, 200 MHz) 5 5.4 (1H, m, vinylic), 5.0 (2H, m, vinylic), 2.0-1.8 (8H, m,methylenes), 1.7 (3H, s, -CH3), 1.4-1.6 (6H, m, methylenes).13C NMR: (C6D6, 50 MHz) 5 218.9 and 216.5 (2 C=0), 138.4 (-QH=CH2), 115.1(-CH=CH2), 43.2 (-CH2), 42.5 (-CH2), 41.7 (-CH2), 33.4 (-CH2), 29.3 (-CH3), 29.2(-CH2), 23.8 (-CH2), 23.7 (-CH2), 23.1 (-CH2).IR (KBr): 3080, 2933, 1715 (C=0), 1645 cm-1.MS: m/e (rel.intensity) 224 (M+, 10), 155 (30), 152 (33), 113 (100), 109 (83), 97 (68),95 (40), 94 (33), 84 (33), 69 (32).Calculated mass: 224.1777, found: 224.1785.Anal. calcd for C14H2402: C, 74.95; H, 10.78. found:C, 74.88; H, 10.75.198bicyclo[10.2.0Jtetradecan-5-one,12-hydroxy-(1R*,12S*)-(±) (8t)-13C NMR: (C6D6, 50 MHz) 5 210.6 (C=0), 77.3 (C-OH), 42.1, 40.4 (methine carbon),39.5 (CH), 38.8 (CH2), 33.9 (CH2), 28.5 (CH2), 27.4 (CH2), 25.9 (CH2), 23.1 (CH2),22.2 (CH2), 22.1 (CH2), 20.4 (CH2).IR (neat): 3600-3300 (OH), 2936, 1703 (C=0) cm-1.MS: nVe (rel.intensity) 224 (Mt 3), 222 (29), 206 (47), 196(15), 165 (28), 163 (37), 149(44), 139 (29), 137 (33), 136 (25), 135 (41), 133 (26), 131 (27), 125 (44), 124 (30), 123(44), 122 (42), 121 (59), 119 (29), 113 (46), 112 (79), 111 (67), 110 (81), 109 (78), 108(46), 107 (83).Calculated mass: 224.1777, found: 224.1783.bicyclo[10.2.0]tetradecan-5-one,12-hydroxy-(1R*,12R*)-(±) (8c)13C NMR: (C6D6, 50 MHz) 8 210.0 (0=0), 77.2 (C-OH), 49.2 (methine carbon), 42.3(CH2), 41.4 (CH2), 36.3 (CH2), 34.5 (CH2), 29.9 (CH2), 28.3 (CH2), 26.4 (CH2), 24.7(CH2), 23.9 (CH2), 22.4 (CH2), 18.8 (CH2).IR (neat): 3600-3200 (OH), 2928, 1703 (0=0) cm-1.MS: m/e (rel.intensity) 224 (Mt 2), 222 (22), 206 (50), 196 (8), 188 (29), 163 (42), 149(46), 145 (32), 135 (43), 133 (32), 131 (33), 125 (33), 124 (29), 121 (63), 119 (37), 112(55), 110 (72), 107 (100), 95 (96), 93 (92), 81(57), 79 (76), 67 (35).Calculated mass: 224.1777, found: 224.1772.The photoproducts from the solution state reaction were not isolated but wereassumed to be the same as their solid state counterparts based on their GLC retentiontimes.199Photolysis of Cyclohexadecane-1,9-dione (9):Irradiation in hexane:Preparative scale solution state reaction of diketone 9 (800 mg) was carried outusing the procedure described for diketone 7. Three major peaks were observed on GLC(DB 17, 190°C) at RT's 4.67, 8.64 and 9.56 min. Products were purified by silica gelcolumn chromatography (Et0Ac:petroleum ether (35-60°C) = 2:98 to 9:91) and werelater identified by spectral analysis.An ene-dione, 15-hexadecene-2,10-dione (9e) (RT 4.67 min), was eluted as awhite solid with 4.5% (v/v) Et0Ac in petroleum ether (54 mg, 6.8%). Recrystallization of9e from EtOAC/petroleum ether gave flakes with mp = 53-54°C. Elution with 7% (v/v)Et0Ac in petroleum ether afforded pure trans-cyclobutanol, bicyclof12.2.0] hexadecan-6-one,14-Hydroxy-(1R*,14S*)-(±) (9t) (RT 8.64 min), as an oil; further elution gave severalfractions of a mixture of compounds 9t and the compound at RT 9.56 min (9c) as an oil(9c:9t = 29:71 by GLC). When the mixture was kept overnight in the refrigerator, a whitesolid formed in the oil. Upon GLC analysis the solid was found to contain compound 9cas the major component. The solid was washed with ice cold petroleum ether andsubjected to several fractional recrystallizations from Et0Ac/petroleum ether to giveprisms (35 mg, 4.4%) with mp = 91-92°C. Compound 9c was identified as bicyclo[12.2.0]hexadecan-6-one,14-Hydroxy-(1R*,14R*)-(±) (9c). The trans-cyclobutanol 9tpresent in the mother liquor (> 92% by GLC) was further purified by columnchromatography and the combined fractions weighed 27 mg (3.4%).Solid state irradiation:Analytical solid state reaction on GLC showed a major peak at RT 9.60 mintogether with two minor peaks at RT's 8.66 and 4.67 min. The solid state products werenot isolated but assumed to be the same as the solution counterparts, based on their GLCretention times.200Analytical photoreactions at 0°C (solid), 10°C (solid), 20°C, 30°C, 40°C, 60°Cwere explored, and the product ratios at 0% conversions are tabulated in Table XVI (a).Irradiation of annealed crystals:Crystals annealed to 50°C (above the transition point of 34°C) were powdered andphotolyzed at 20°C on an analytical scale as described in the general experimental section.Product ratios at 0% conversion are tabulated in Table XVI(a).15-hexadecene-2,10-dione (9e)1H NMR: (CDC13, 300 MHz) 8 5.8 (1H, m, -CH=CH2), 5.0 (2H, m, -CH=CH2), 2.4(6H, m, -CH2-C=0), 2.2 (3H, s, -CH3), 2.1 (2H, two overlapping triplets, -C112-CH=CH2), 1.6-1.5 (6H, m, methylenes), 1.4-1.2 (8H, m, methylenes).13C NMR: (CDC13, 75 MHz) 8 211.4 and 209.3 (2C=0), 138.5 (-CH=CH2), 114.6(-CH=CH2), 43.7 (CH), 42.7 (CH2), 42.6 (CH2), 33.5 (CH2), 29.9 (CH3), 29.2 (CH2),29.0 (CH2), 28.9 (CH2), 29.4 (CH2), 23.7 (CH2), 23.3 (CH2).IR (KBr): 3081, 2932, 1704 ((2=0), 1645 cm-1.MS: ink (rel.intensity) 252 (Mt, 7), 184 (39), 169 (31), 111 (33), 109 (65), 108 (28), 98(87), 83 (84), 71(56), 69 (32), 68 (49), 67 (30), 58 (34), 55 ( 100), 43 (37), 41(51).Calculated mass: 252.2089, found: 252.2094.Anal. calcd for C16H2802: C, 76.14; H, 11.18. found: C, 76.30; H, 11.10.bicyclo[12.2.0Thexadecan-6-one,14-Hydroxy-(1R*,14S*)-a) (9t)13C NMR:(C6D6, 75 MHz) 8 210.6 (C=0), 78.3 (C-OH), 42.3, 41.6 (methine), 40.9(CH2), 33.5 (CH2), 29.0 (CH2), 27.5 (CH2), 26.8 (CH2), 26.7 (CH2), 26.4 (CH2), 23.7(CH2), 23.4 (CH2), 22.7 (CH2), 22.0 (CH2).IR (neat): 3600-3300 (OH), 2933, 1703 (C=0) cm-1.201MS: m/e (rel.intensity) 252 (Mt, 5), 224 (1), 206 (10), 126 (37), 111 (35), 108 (35), 98(75), 97 (26), 95 (27), 83 (61), 81(29), 71(33), 69 (30), 67 (30), 55 (100), 43 (43), 41(41).Calculated mass: 252.2089, found: 252.2085.bicyclo[12.2.0]hexadecan-6-one,14-Hydroxy-(1R*,14S*)-(±) (9c)I-3C NMR: (C6D6, 75 MHz) 8 209.1 (C=0), 76.3 (f-OH), 49.8 (methine), 40.6 (CH2),40.4 (CH2), 34.6 (CH2), 33.3 (CH2), 29.5 (CH2), 27.0 (CH2), 26.9 (CH2), 25.6 (CH2),25.1 (CH2), 23.3 (CH2), 22.5 (CH2), 20.1 (CH2), 19.1 (CH2).IR (KBr): 3600-3300 (OH), 2927, 1703 (C=0) cm-1.MS: m/e (rel.intensity) 252 (M+, 4), 224 (1), 127 (26), 126 (47), 111 (44), 109 (35), 108(41), 98 (100), 97 (32), 95 (30), 84 (29), 83 (83), 81(32), 71(47), 69 (39), 68 (29), 67(35), 58 (32), 57 (26), 55 (88), 43 (71), 41(75).Calculated mass: 252.2089, found: 252.2080.Anal. calcd for C16H2802: C, 76.14; H, 11.18. found:C, 76.25; H, 11.06.For cis-cyclobutanol 9c, the stereochemistry at the ring junction was confirmed byX-ray crystallographic analysis.Photolysis of cyclooctadecane-1,10-dione (10):Irradiation in hexane :Preparative scale solution state reaction of diketone 10 (750 mg) was carried outusing the procedure described for diketone 6. Three new peaks were observed on GLC(DB 17, 200°C) at RTs 6.19, 10.97 and 12.54 min. Products were purified by silica gelcolumn chromatography (Et0Ac:petroleum ether (35-60°C) = 3:97 to 9:91) and werelater identified by spectral analysis.An ene-dione, 17-octadecene-2,11-dione (10e) (RT 6.19 min) was eluted as awhite solid with 4% (v/v) Et0Ac in petroleum ether (54 mg, 7.2%). Recrystallization of20210e from Et20-petroleum ether gave flakes with mp = 58-59°C. Elution with 7% (v/v)Et0Ac in petroleum ether afforded pure trans-cyclobutanol, bicyclo[14.2.0] octadecan-7-one-16-Hydroxy-(1R*,16S*)-(±) (100 (RT 10.97 mm) as an oil (40 mg, 5.4%). Severalattempts made to isolate the compound at RT 12.54 (10c) min by conventional columnchromatography were unsuccessful. Based on its GLC retention time relative to the othertwo photoproducts, compound 10c was assumed to be the cis-cyclobutanol,bic yclo [14.2.0] octadecan-7-one-16-Hydroxy-(1R*,16R*)-(±).Solid state reactionAnalytical solid state reaction showed a major peak at RT 10.97 min and twominor peaks at RT's 6.19 and 12.54 min. The solid state products were not isolated butassumed to be the same as the solution counterparts, based on their GLC retention times.Analytical photoreactions at 20°C, 30°C, 40°C, 60°C, 80°C and 90°C were alsoexplored and the product ratios at 0% conversions are tabulated in Table XVI(b).Photolysis of annealed crystals :Crystals annealed to 90°C (above the transition point of 86°C) were photolyzed onan analytical scale as described in the general experimental section. Product ratios at 0%conversion are tabulated in Table XVI(b).17-octadecene -2,11 -dione (10e)1H NMR: (CDC13, 400 MHz) 8 5.8 (1H, m, -CH=CH2 ), 4.9 (2H, m, -CH=CH2 ), 2.4(6H, m, -CH2-C=0), 2.15 (3H, s, -CH3), 2.05 (2H, two overlapping triplets, -Cf_12-CH=CH2), 1.55 (6H, m, methylenes), 1.5-1.2 (8H, m, methylenes).13C NMR:(CDC13, 75 MHz) 8 211.5 and 209.3 (2 C=0), 138.8 (-H=CH2), 114.3(-CH=CH2), 43.7 (CH2), 42.7 (CH2), 42.6 (CH2), 33.5 (CH2), 29.8 (CH3), 29.6 (CH2),29.2 (CH2), 29.1 (CH2), 29.0 (CH2), 28.7 (CH2), 28.6 (CH2), 23.7 (CH2), 23.6 (CH2).IR (KBr): 3081, 2931, 1704 (C=0), 1645 cm-1.MS: mie (rel.intensity) 280 (M+, 0.3), 97 (20), 58 (26), 55 (100), 43 (96), 41(42).203Calculated mass: 280.2403, found: 280.2397.Anal. calcd for C18143202: C, 77.14; H, 11.43. found:C, 77.19; H, 11.57.bicyclo[14.2.0] octadecan-7-one-16-Hydroxy-(1R*,16S*)-(±) (10t)13C NMR: (C6D6, 75 MHz) 8 210.0 (C=0), 76.7 (C-OH), 42.2 (methine carbon), 42.0(CH2), 41.7 (CH2), 41.5 (CH2), 34.4 (CH2), 30.2 (CH2), 28.6 (CH2), 28.5 (CH2), 28.1(CH2), 28.0 (CH2), 27.0 (CH2), 26.9 (CH2), 24.1 (CH2), 22.9 (CH2), 22.7 (CH2), 21.1(CH2).IR (neat): 3600-3300 (OH), 2929, 1708 (C=0) cm-1.MS: nVe (rel.intensity) 280 (Mt, 1.0), 252 (4), 97 (28), 83 (28), 69 (26), 55 (100), 43 (45),41(44).Calculated mass: 280.2403, found: 280.2396.Photolysis of Cycloeicosan-1,11-dione (11):Irradiation in hexane :Compound (11) (1.9 g) was preparatively photolyzed in hexane using the standardprocedure described for compound 7. Analysis of the reaction mixture on GLC (DB 17,200 °C) showed three new peaks at RT's 5.29, 9.05, 9.87 min. Products were purified bysilica gel column chromatography (Et0Ac: petroleum ether (35-60°C) = 2:98 to 9:91) andwere identified by spectral analysis.An ene-dione, 19-eicosene-2,12-dione (11e) (RT 5.29 min) was eluted as a whitesolid with 2.5% (v/v) ethyl acetate in petroleum ether (115 mg, 6.2%). Recrystallizationof lie from Et20/petroleum ether gave flakes with mp = 68-69°C. Elution with 6% (v/v)Et0Ac in petroleum ether gave a trans-cyclobutanol, bicyclo[16.2.0]eicosan-8-one,18-Hydroxy-(1R*,18S*)- -CL) (11t). Evaporation of the solvent initially gave an oil, butthis slowly solidified at room temperature to give a white solid (50 mg, 2.7% yield).Recrystallization of lit from EtO/pet-ether gave prisms with mp = 31-32°C. A cis-204cyclobutanol, bicyclo[16.2.0]eicosan-8-one,18-Hydroxy-(1R*,18R*)-(-) (11c) was elutedas a white solid with 7% (v/v) Et0Ac in petroleum ether (15 mg, 0.8% yield) with mp =54-55°C.Solid state reaction:Analytical studies indicated the development of only one major peak on GLC(DB17, 200°C) at RT 9.94 min with slight traces of other peaks. Preparative solid statephotolysis of diketone 11 (1.53 g) was carried out as described in the general experimentalsection. After 8% total conversion, the product was purified by silica gel columnchromatography (Et0Ac:petroleum ether (35-60°C) = 7:93) as a white solid (67 mg,44%) and was later identified as compound lit.For the trans-cyclobutanol photoproduct llt, the stereochemistry at the ringjunction was confirmed by an X-ray crystal structure.19-eicosene-2,12-dione (11e)1H NMR: (C6D6, 200 MHz) 8 5.6 (1H, m, vinylic), 4.9 (2H, m, vinylic), 2.0 (8H, m,methylenes), 1.7 (3H, s, -CH3), 1.5 (6H, m, methylenes), 1.2 (16H, bs, methylenes).13C NMR: (C6D6, 50 MHz) 5 213.0 and 218.0 (2 C=0), 139.1 (-CH=CH2), 114.5(-CH=CH2), 43.4 (-CH2), 42.63 (CH2), 42.61 (CH2), 34.1 (CH2), 29.8 (CH3), 29.7(CH2), 29.6 (CH2), 29.5 (CH2), 29.46 (CH2), 29.41 (CH2), 29.3 (CH2), 29.2 (CH2), 29.1(CH2), 24.1 (CH2), 24.03 (CH2), 24.02 (CH2).IR (KBr): 3078, 2931, 1705 (0=0), 1645 cm4.MS: tnie (rel.intensity) 308 (M+, 0.5), 71(47), 69 (74), 58 (43), 55 (93), 43 (100), 41(54).Calculated mass: 308.2717, found: 308.2714.Anal. calcd for C20H3602: C, 77.87; H, 11.76. found: C, 77.84; H, 11.76.205bicyclo[16.2.0]eicosan-8-one, 18-Hydroxy-(1R*,18S*)-(±,) (11t)13C NMR: (C6D6, 50 MHz) 5 210.0 (C=0), 77.3 (C-OH), 43.1 (methine carbon), 42.3(CH2), 42.1 (CH2), 42.0 (CH2), 33.9 (CH2), 29.9 (CH2), 28.97 (CH2), 28.96 (CH2), 28.6(CH2), 28.32 (CH2), 28.28 (CH2), 28.23 (CH2), 27.5 (CH2), 27.1 (CH2), 24.0 (CH2),23.7 (CH2), 22.9 (CH2), 21.3 (CH2).IR (KBr): 3600-3300 (OH), 2932, 1708 (C=0) cm-1.MS: mie (rel.intensity) 308 (Mt, 2), 280 (2), 71(25), 69 (37), 58 (27), 55 (100), 43 (63),41(64).Calated mass: 308.2717, found: 308.2724.Anal. calcd for C201-13602: C, 77.87; H, 11.76. found: C, 77.71; H, 11.81.bicyclo[16.2.0]eicosan-8-one, 18-Hydroxy-(1R*,18R*)-(±) (11c)13C NMR: (C6D6, 50 MHz) 5 210.0 (C=0), 76.7 (C-OH), 50.1 (methine carbon), 42.4(CH2), 42.1 (CH2), 33.8 (CH2), 33 5 (CH), 29.8 (CH2), 29.6 (CH2), 29.2 (CH2), 28.5(CH2), 28.4 (CH2), 28.2 (CH2), 28.0 (CH2), 27.7 (CH2), 27.3 (CH2), 24.2 (CH2), 23.6(CH2), 22.1 (CH2), 19.1 (CH2).IR (KBr): 3400-3600 (OH), 2922, 1709 (C=0) cm-1.MS: mie (rel.intensity) 308 (M-I-, 5), 280 (2), 149 (25), 111 (46), 98 (71), 81(46), 69(43), 55 (100), 43 (50), 41(83).Calculated mass: 308.2717, found: 308.2763.Anal. calcd for C201-13602: C, 77.87; H, 11.76. found: C, 77.81; H, 11.80.Photolysis of cyclodocosane-1,12-dione (12)Irradiation in hexane:Diketone 12 (820 mg) was preparatively photolyzed in hexane using the standardprocedure described for compound 7. The reaction mixture on GLC (DB 17, 235°C)206showed three new peaks at RT's 5.92, 9.53, 10.58 min. Products were purified by silicagel column chromatography (Et0Ac:petroleum ether = 3:97 to 7:93) and identified byspectral analysis.An ene-dione 21-docosene-2,13-dione (12e) (RT 5.92 min), was eluted as a whitesolid with 3.5% (v/v) Et0Ac in petroleum ether (87 mg, 10.6% yield). Recrystallizationof 12e from Et20/petroleum ether gave flakes with mp = 72-73 °C. A trans-cyclobutanol,bicyclo[18.2.01docosan-9-one,20-Hydroxy-(1R*,20S*)-(±) (12t) (RT 9.53 mm) waseluted as an oil with 6% (v/v) Et0Ac in petroleum ether (29 mg, 3.6% yield). A cis-cyclobutanol, bic yclo [18.2.0] docosan-9- one,20-Hydroxy-(1R*,20R*)-(±) (12c) (RT10.58 min) was eluted as an oil with 6.5% (v/v) Et0Ac in petroleum ether (21 mg, 2.5%yield).Solid state irradiation:Preparative solid state photolysis of diketone 12 was carried out as described inthe general procedure. GLC analysis indicated the development of one major peak (RT9.37 min) and traces of several minor peaks. After 15% conversion to products the finalmixture was subjected to silica gel column chromatography and the major product wasisolated (64 mg, 8.5% yield) and identified as cyclobutanol 12t.21-docosene-2,13 -dione (12e)111 NMR: (CDC13, 400 MHz) 5 5.8 (1H, m, vinylic), 4.9 (2H, m, vinylic), 2.4 (6H, m,-CH2-C=0), 2.1 (3H, s, -CH3), 2.0 (2H, two overlapping triplets, -C112-CH=CH2), 1.6(6H, bs, methylenes), 1.3 (20H, bs, methylenes).13C NMR: (C6D6 75 MHz) 5 208.8 and 206.3 (2 C=0), 139.2 (-fH=CH2), 114.6(-CH=1H2), 43.4 (CH), 42.7 (CH2), 34.2 (CH2), 29.9 (-CH3), 29.8 (CH2), 29.7 (CH2),29.63 (CH2), 29.57 (CH2), 29.4 (CH2), 29.3 (CH2), 24.2 (CH2), 24.1 (CH2).JR (KBr): 3081, 2917, 1705 (C=0), 1645 cm4.207MS: m/e (rel.intensity) 336 (Mt, 2), 125 (31), 109 (26), 95 (39), 83 (48), 81(39), 71(45), 69 (71), 67 (33), 58 (31), 55 (83), 43 (100), 41(58).Calculated mass: 336.3030, found: 336.3026.Anal. calcd for C22H4002: C, 78.51; H, 11.98. found: C, 78.50; H, 11.92.bicyclo[18.2.0]docosan-9-one,20-Hydroxy-(1R*,20S*)-Ct) (12t)13C NMR: (C6D6, 75 MHz) 5 209.7 (C=0), 76.6 (C-OH), 43.4 (methine carbon), 42.4(CH2), 42.2 (CH2), 42.1 (CH2), 34.2 (CH2), 30.7 (CH2), 29.4 (CH2), 29.1 (CH2), 29.0(CH2), 28.8 (CH2), 28.73 (CH2), 28.68 (CH2), 28.3 (CH2), 27.9 (CH2), 27.3 (CH2), 24.0(CH2), 23.5 (CH2), 22.9 (CH2), 21.0 (CH2).IR (neat): 3600-3300 (OH), 2928, 1709 (0=0) cm-1.MS: m/e (rel.intensity) 336 (Mt, 7), 308 (14), 71(25), 69 (37), 58 (27), 55 (100), 43(63), 41(64).Calculated mass: 336.3030, found: 336.3027.bicyclo[18.2.0]docosan-9-one,20-Hydroxy-(1R*,20R*)-a) (12c)13C NMR:(C6D6, 75 MHz) 5 210.0 (0=0), 76.7 (C-OH), 43.4 (methine carbon), 42.5(CH2), 42.2 (CH2), 42.1 (CH2), 34.2 (CH2), 30.7 (CH2), 29.5 (CH2), 29.1 (CH2), 29.0(CH2), 28.8 (CH2), 28.7 (CH2), 28.3 (CH2), 28.0 (CH2), 27.3 (CH2), 24.1 (CH2), 23.5(CH2), 23.0 (CH2), 21.1 (CH2).IR (neat): 3600-3400 (OH), 2922, 1704 (C=0) cm-1.MS: m/e (rel.intensity) 336 (Mt, 1), 308 (4), 83 (31), 69 (42), 67 (31), 58 (31), 55 (100),43 (54), 41(58).Calculated mass: 336.3030, found: 336.3022.208Photolysis of cyclotetracosane-1,13-dione (13)Irradiation in hexane :Diketone 13 (1.2 g) was preparatively photolyzed using the standard proceduredescribed for compound 7. The reaction mixture on GLC (DB 17, 245 °C) indicated threenew peaks at RT's 6.33, 10.07 and 11.01 min. Products were purified by silica gel columnchromatography (Et0Ac:petroleum ether = 3:97 to 7:93) and characterized by spectralanalysis.An ene-dione, 23-tetracosene-2,14-dione (13e) (RT 6.33 nun) was eluted as awhite solid with 3% (v/v) Et0Ac in petroleum ether (107 mg, 8.9% yield).Recrystallization of 13e from Et20/petroleum ether gave a powdery solid with mp = 78-80°C. A trans-cyclobutanol, bicyclo[20.2.0]tetracosan-10-one, 22-hydroxy-(1R*,22S*)-(±) (13t) (RT 10.07 min) was eluted as an oil with 6.5% (v/v) Et0Ac in petroleum ether(50 mg, 4.2% yield). A cis-cyclobutanol, bicyclo[20.2.0]tetracosan-10-one, 22-hydroxy-(1R*,22R*)-(±) (13c) (RT 11.01 min) was eluted as an oil with 7% (v/v) Et0Ac inpetroleum ether (30 mg, 2.5% yield).Solid state reaction Analytical solid state photolysis indicated the development of one major peak onGLC (DB 17, 245 °C) at RT 11.05 min with traces of minor peaks. Preparative solid statephotolysis of compound 13 (600 mg) was carried out as described in the generalprocedure upto 18% conversion to products. The major product was purified by silica gelcolumn chromatography (Et0Ac: petroleum ether = 7:93) as an oil (63 mg, 10.5% yield)and was later identified as the cis-cyclobutanol 13c. The product ratio at 0% conversion istabulated in Table IV.20923-tetracosene-2,14-dione (13e)1H NMR: (CDC13, 200 MHz) 8 5.9 (1H, m, vinylic), 4.95 (2H, m, vinylic), 2.4 (6H, m,-CH2-C=0), 2.1 (3H, s, -CH3), 2.0 (2H, two overlapping triplets, -CE2-CH=CH2), 1.5(6H, bs, methylenes), 1.1 (24H, bs, methylenes).13C NMR: (CDC16, 50 MHz) 8 211.5 and 209.1 (2C=0), 139.1 (-fH=CH2), 103.1(-CH=fH2), 43.7 (CH2), 42.7 (CH2), 33.7 (CH2), 29.8 (CH3), 29.5 (CH2), 29.4 (CH2),29.3 (CH2), 29.25 (CH2), 29.21 (CH2), 29.12 (CH2), 29.01 (CH2), 28.8 (CH2), 23.8(CH2).IR (KBr): 3080, 2931, 1705 (C=0), 1646 cm-1.MS: m/e (rel.intensity) 364 (Mt 2), 125 (28), 109 (27), 97 (30), 95 (41), 83 (62), 81(45), 71(50), 69 (48), 67 (34), 58 (32), 57 (33), 55 (100), 43 (85), 41(52).Calculated mass: 364.3343, found: 364.3330.Anal. calcd for C24H4402: C, 79.06; H, 12.16. found:C, 79.00; H, 12.19.bicydo[20.2.0]tetracosan-10-one, 22-hydroxy-(1R*,22S*)-(±) (13t)13C NMR: (C6D6, 50 MHz) 8 210.0 (0=0), 77.0 (f-OH), 43.5 (methine carbon), 42.3(CH2), 42.2 (CH2), 42.1 (CH2), 34.0 (CH2), 30.2 (CH2), 29.6 (CH2), 29.4 (CH2), 29.1(CH2), 29.0 (CH2), 28 71 (CH2), 28.67 (CH2), 28.63 (CH2), 28.60 (CH2), 27.4 (CH2),24.1 (CH2), 23.9 (CH2), 23.4 (CH2), 21.1 (CH2).IR (neat): 3650-3400 (OH), 2925, 1698 (C=0) cm-1.MS: ink (rel.intensity) 364 (Mt 7), 336 (12), 111 (25), 97 (29), 95 (43), 83 (49), 81(44), 71(39), 69 (47), 67 (37), 58 (29), 57 (34), 55 (100), 43 (33), 41(48).Calculated mass: 364.3343, found: 364.3355.bicyclo[20.2.0]tetracosan-10-one, 22-hydroxy-(1R*,22R*)-(±) (13c)13C NMR: (C6D6, 50 MHz) 5 209.5 (C=0), 76.7 (a-OH), 50.1 (methine carbon), 42.5(CH2), 42.2 (CH2), 34.0 (CH2), 33.9 (CH2), 30.2 (CH2), 29.83 (CH2), 29.79 (CH2),21029.54 (CH2), 29.2 (CH2), 29.14 (CH2), 29.10 (CH2), 29.02 (CH2), 28.85 (CH2), 28.79(CH2), 28.76 (CH2), 28.69 (CH2), 28.1 (CH2), 24.1 (CH2), 24.0 (CH2), 22.7 (CH2), 19.2(CH2).IR (neat): 3600-3440 (OH), 2923, 1708 (C=0) cm-1.MS: m/e (rel.intensity) 364 (Mt, 3), 336 (6), 97 (27), 95 (41), 83 (45), 81(46), 71(36),69 (44), 67 (39), 58 (27), 57 (31), 55 (100), 43 (27), 43 (37), 41(51).Calculated mass: 364.3343, found: 364.3353.Photolysis of cyclohexacosane-1,14-dione (14)Solid state irradiation :Photolysis of the two crystal modifications of diketone 14, plates and needles,indicated the development of two new peaks corresponding to the photoproducts on GLCanalysis. Plates upon irradiation showed a major peak on GLC (DB 17, 260°C) atRT 10.30 min and a minor peak at RT 9.47 min, where as needles gave the above peaks atRT's 9.43 and 10.26 min respectively.Plate crystals (14P)Preparative solid state photolysis was carried out with 600 mg of diketone asdescribed in the general procedure. The major photoproduct was isolated by columnchromatography(silica gel, Et0Ac: petroleum ether = 9:91) as a white solid (73 mg,12.2% yield, mp = 42-43°C) and was later identified as a cis-cyclobutanol derivative,bicyclo[22.2.0Thexacosan-11-one, 24-Hydroxy-(1R*,24R*)-(_±) (14c).Needle crystals (14N)Irradiation was carried out with 750 mg of diketone and the major photoproductwas isolated by column chromatography (silica gel, Et0Ac:petroleum ether = 8:92) as anoil (47 mg, 6.3% yield). The product was identified as a trans-cyclobutanol derivative,bicyclo[22.2.0Thexacosan-11-one, 24-Hydroxy-(1R*,24S*)-(±) (14t).211Irradiation in hexane:Diketone 13 (800 mg) was preparatively photolyzed using the standard proceduredescribed for diketone 7. The reaction mixture on GLC (DB 17, 260°C) indicated thedevelopment of three new peaks at RT's 6.03, 9.43 and 10.40 min. After 17% totalconversion, products were purified by silica gel column chromatography(Et0Ac:petroleum ether = 3:97 to 9:91) and characterized by spectral analysis.Elution with 6% (v/v) Et0Ac in petroleum ether yielded 58 mg (7.2%) of25-hexacosene-2,15-dione (14e) (RT 6.03 min) as a white solid. Recrystallization fromEt20/petroleum ether gave a powder with mp = 82-83°C. Compounds corresponding topeaks at RT's 9.43 and 10.40 min were eluted together with 8% (v/v) Et0Ac in petroleumether, and were shown by co-injection experiments to have retention times identical tothose of 14t and 14c, respectively.A solution of this mixture in a Et20/petroleum ether solvent system afforded awhite solid upon cooling in ice. After filtration, GLC analysis of this solid showed it tocontain 82% of the compound corresponding to RT 10.40 min. Several fractionalrecrystallizations from Et20/petroleum ether gave 97% pure white solid (6 mg, 1.2%),which was later identified as cis-cyclobutanol 14c. Spectral analysis of the rest of themixture obtained from the combined mother liquors revealed the compound with RT 9.43min to be the trans-cyclobutanol 14t.Analytical photolysis :Plate crystals annealed to 60°C (5 cycles) were powdered and subjected toirradiation at 20°C; development of a single major peak at RT 9.43 min together with aminor peak at RI 10.25 min were observed on GLC (DB 17, 260°C). Analyticalphotoreactions of virgin crystals (plates and needles) were also explored at 0°C, 20°C,40°C, 60°C and 65°C. Product ratios of both the plates and the needles at 60°C andabove were found to be close to that observed for needles and annealed plates at 20°C.The peaks at RT's 9.43 min and 10.25 min were assumed to be compounds 14t and 14c212respectively, based on their GLC retention times. Product ratios at 0% percent conversionfor all the above reactions are tabulated in Table XIV.25-hexacosene-2,15-dione (14e)1H NMR: (CDC13, 200 MHz) 8 5.8 (1H, m, -CH=CH2), 4.9 (2H, m, -CH=CH2), 2.4(6H, m, -CH2-C=0), 2.1 (3H, s, -CH3), 2.0 (2H, two overlapping triplets, -CLI2-CH=CH2), 1.6 (6H, bs, methylenes), 1.2 (24H, bs, methylenes).13C NMR: (CDC16, 75 MHz) 5 211.6 and 209.3 (2 C=0), 139.1 (-CH=CH2), 114.0(-CH=QH2), 43.8 (CH2), 42.8 (CH2), 33.7 (CH2), 29.8 (-CH3), 29.5 (CH2), 29.3 (CH2),29.21 (CH2), 29.17 (CH2), 29.13 (CH2), 29.0 (CH2), 28.9 (CH2), 23.8 (CH2).IR (KBr): 3074, 2917, 1705 (C=0), 1645 cm4.MS: m/e (rel.intensity) 392 (M-F, 13), 254 (54), 239 (25), 196 (35), 125 (39), 111 (27),109 (29), 97 (48), 96 (35), 95 (51), 83 (58), 81(47), 71(57), 69 (52), 67 (28), 58 (41),55 (100), 43 (81), 41(39).Calculated mass: 392.3656, found: 392.3653.Anal. calcd for C26H4802: C, 79.53; H, 12.32. found: C, 79.40; H, 12.40.bicyclo[22.2.0]hexacosan-11-one, 24-Hydroxy-(1R*,24S*)-(±) (14t).13C NMR: (C6D6, 75 MHz) 8 209.6 (C=0), 76.7 (.-OH), 43.7 (methine carbon), 42.5(CH2), 42.2 (CH2), 42.1 (CH2), 34.2 (CH2), 30.4 (CH2), 29.9 (CH2), 29.5 (CH2), 29.4(CH2), 29.3 (CH2), 29 2 (CH2), 29.13 (CH2), 29.10 (CH2), 29.0 (CH2), 28.8 (CH2), 27.6(CH2), 24.1 (CH2), 23.8 (CH2), 23.4 (CH2), 20.9 (CH2).IR (neat): 3600-3300 (OH), 2926, 1713 (C=0) cm1.MS: m/e (rel.intensity) 392 (Mt 5), 364 (11), 125 (25), 109 (29), 97 (37), 96 (25), 95(51), 83 (46), 81(51), 71(39), 69 (50), 67 (40), 58 (27), 57 (36), 55 (100), 43 (32), 41(46).Calculated mass: 392.3656, found: 392.3649.213bicyclo[22.2.0]hexacosan-11-one, 24-Hydroxy-(1R*,24R*)-(±) (14c).13C NMR: (C6D6, 75 MHz) 5 204.2 (C=0), 76.7 (C-OH), 50.1 (methine carbon), 42.2(CH2), 42.16 (CH2), 34.2 (CH2), 34.0 (CH2), 30.1 (CH2), 29.9 (CH2), 29.31 (CH2),29.27 (CH2), 29.12 (CH2), 29.08 (CH2), 29.04 (CH2), 28.99 (CH2), 28.9 (CH2), 28.73(CH2), 28.66 (CH2), 28.0 (CH2), 24.0 (CH2), 23.9 (CH2), 22.8 (CH2), 19.2 (CH2).IR (KBr) 3560-3300 (OH), 2927, 1713 (C=0) cm-1.MS: m/e (rel.intensity) 392 (Mt, 4), 364 (11), 109 (25), 97 (36), 83 (47), 81(41), 71(42), 69 (51), 67 (51), 58 (32), 57 (33), 55 (100), 43 (33), 43 (28), 41(45).Calculated mass: 392.3656, found: 392.3642.Anal. calcd for C26H4802: C, 79.53; H, 12.32. found:C, 79.26; H, 12.40.6.2.3. Photochemistry of Non-diametric Diketone.Photolysis of Cyclohexadecane-1,8-dione (15)Irradiation in hexane:Diketone 15 (1.5 g) was preparatively photolyzed using the standard proceduredescribed for diketone 7. The reaction mixture on GLC (DB 17, 175°C) showed four newpeaks at RT's 6.39, 11.90, 13.10 and 13.51 min. Products were purified by silica gelcolumn chromatography (Et0Ac:petroleum ether(v/v) = 3:97 to 12:88) and characterizedby spectral analysis.The product corresponding to the peak at RT 6.39 min was eluted as a white solidwith 3.5% (v/v) Et0Ac in petroleum ether (35-60 °C) (68 mg, 4.5% yield).Recrystallization from Et20/petroleum ether solvent system gave flakes with mp = 41-42°C. Spectral analysis (1H NMR and 13C NMR) revealed this solid to be a mixture oftwo regioisomers, 15-hexadecene-2,9-dione (15e1) and 15-hexadecene-2,11-dione (15e2).The peak at RT 11.91 min was eluted as an oil with 7% (v/v) EtOAc in petroleum ether214(35-60°C) (72 mg, 5.0% yield), and was later identified as a mixture of two trans-cyclobutanol regioisomers, bicyclo[12.2.0]hexadecan-7-one,14-Hydroxy-(1R*,14S*)-(±)(15t1) and bicyclo[12.2.0] hexadecan-5-one,14-Hydroxy-(1R*,14S*)-(±) (15t2). Attemptmade to separate the regioisomers of the cleavage products (15e1 and 15e2) or the trans-cyclobutanols (15t1 and 15t2) were not successful. Elution with 7.5% (v/v) Et0Ac inpetroleum ether gave pure cis-cyclobutanol, bicyclo[12.2.0]hexadecan-7-one,14-Hydroxy-(1R*,14R*)-(±) (15c1) (RT 13.51 min) as a white solid (23 mg, 1.5% yield).Recrystallization of 15c1 from hexane gave prism and needle shaped crystals in the samebatch. Manually separated needle and plate crystals showed identical melting points (122-123°C) and infrared spectra. Further elution (75 fractions) gave a mixture of 15c1 and thecompound (15c2) corresponding to the peak at RT 13.10 min. In the last few fractions,pure 15c2 was isolated and was later identified as a regioisomer of compound 15c1,bicyclo[12.2.0]hexadecan-5-one,14-Hydroxy-(1R*,14R*)-(±) (15c2). Recrystallization of15c2 gave colorless plates (18 mg, 1.2% yield) with mp = 82-83°C.The regiochemistry and the stereochemistry at the ring junction of the cis-cyclobutanols were determined by X-ray crystallographic analysis.Solid state reaction :Preparative solid state photolysis of compound 15 (650 mg) was carried out asdescribed in the general procedure. GLC (DB 17, 175°C) analysis indicated thedevelopment of a single major product at RT 13.50 min with traces of minor peaks. Themajor product was purified (81 mg, 13% yield), and was later identified as the cis-cyclobutanol 15c1.Analytical irradiation:Photoreactions of virgin crystals were also explored at 0°C, 10°C, 20°C, 30°C,40°C and 60°C. Crystals were also annealed to 40°C (above the first transition point at37°C) and 60°C (above the second transition point at 55°C), and were subjected to215irradiation at 20°C. Product ratios at 0% conversion were calculated and compiled inTable XVIc.15-hexadecene-2,9-dione (10e1) and 15-hexadecene-2,11-dione (15e2):1H NMR: (C6D6, 200 MHz) 5 5.8-5.6 (2H, m, -CH=CH2), 5.0 (4H, m, -CH=CE2), 2.0(16H, m, methylenes), 1.7 (6H, two singlets, -CH3), 1.5 (12H, m, methylenes), 1.1 (16H,m, methylenes).13C NMR: (C6D6, 100 MHz) 5 208.7, 208.5, 206.3 and 206.2 (4 C=0), 139.0, 138.4(2-CH=CH2), 115.1 and 114.6 (2 -CH=CH2), 43.3 (CH), 43.2 (CH2), 42.6 (CH2),42.53 (CH2), 42.47 (CH2), 41.7 (CH2), 35.0 (CH2), 33.9 (CH2), 33.4 (CH), 29.62(CH2), 29.61 (CH2), 29.5 (CH2), 29.4 (CH2), 29.3 and 29.2 (2 -CH3), 29.03 (CH2), 29.0(CH2), 24.03 (CH2), 23.98 (CH2), 23.89 (CH2), 23.86 (CH2), 23.81 (CH2), 23.1 (CH2),23.0 (CH2).IR (KBr): 3082, 2932, 1705 (C=0), 1645 cm4.MS: ink (rel.intensity) 252 (Mt, 2), 109 (25), 97 (25), 69 (30),55 (60), 43 (100), 41(44).Calculated mass: 252.2089, found: 252.2097.Anal. calcd for C16H2802: C, 76.14; H, 11.18. found:C, 76.19; H, 11.19.bicyclo[12.2.0]hexadecan-7-one,14-Hydroxy-(1R*,14S*)-(1) (15t1) and bicyclo[12.2.0] hexadecan-5-one,14-Hydroxy-(1R*,14S*)-(±) (15t2) :13C NMR: (C6D6, 50 MHz) 5 210.24 and 210.21 (2 C=0), 77.4 and 77.3 (2 -0H),41.8 (CH2), 41.31 (CH2),41.29 (CH2), 40.92 (CH2), 40.84 (methine), 40.8 (CH2), 40.7(CH2), 40.6 (CH2), 40.5 (CH2), 34.4 (CH2), 34.2 (CH2), 29.6 (CH2), 28.4 (CH2), 27.8(CH2), 27.42 (CH2), 27.37 (CH2), 27.30 (CH2), 26.9 (CH2), 26.5 (CH2), 26.4 (CH2),24.2 (CH2), 23.9 (CH2), 23.8 (CH2), 22.6 (CH2), 22.0 (CH2), 21.2 (CH2), 21.1 (CH2),20.2 (CH2).216IR (neat): 3600-3200 (OH), 2936, 1708 (C=0) cm-1.MS: mile (rel.intensity) 252 (Mt 9), 224 (20), 125 (37), 113 (31), 112 (66), 111 (38), 97(70), 95 (37), 85 (28), 84 (92), 83 (44), 81(37), 71(40), 69 (63), 67 (34), 58 (42), 57(29), 55 (87), 43 (100),41 (79).Calculated mass: 252.2089, found: 252.2092.bicyclo[12.2.0]hexadecan-7-one,14-Hydroxy-(1R*,14R*)-(±) (15c1)13C NMR: (C6D6, 100 MHz) 5 210.0 (C=0), 76.2 (C-OH), 50.0 (methine), 43.2 (CH2),38.0 (CH2), 34.3 (CH2), 31.2 (CH2), 29.2 (CH2), 27.6 (CH2), 26.9 (CH2), 25.7 (CH2),25.3 (CH2), 23.1 (CH2), 21.4 (CH2), 19.4 (CH2), 19.0 (CH2).IR (KBr): 3417, broad (OH), 2927, 1692 (C=0) cm-1.MS: m/e (rel.intensity) 252 (M1-, 5), 224 (3), 125 (40), 113 (26), 113 (53), 112 (65), 109(42), 107 (25), 98 (43), 97 (66), 95 (52), 94 (40), 85 (42), 84 (58), 83 (58), 82 (40), 81(48), 79 (34), 71(49), 69 (65), 67 (49), 58 (51), 55 (100), 53 (29), 43 (70), 41(73), 39(34).Calculated mass: 252.2089, found: 252.2097.Anal. ca1cd for C16H2802: C, 76.14; H, 11.18. found: C, 76.01; H, 11.21.bicyclo[12.2.01hexadecan-5-one,14-Hydroxy-(112*,14R*)-(±) (15c2)13C NMR: (C6D6, 50 MHz) 5 209.8 (CO), 76.6 (C-OH), 50.0 (methine), 42.0 (CH2),40.6 (CH2), 35.2 (CH2), 35.0 (CH2), 29.9 (CH2), 26.64 (CH2), 26.59 (CH2), 26.0 (CH2),24.7 (CH2), 24.3 (CH2), 21.9 (CH2), 20.7 (CH2), 18.6 (CH2).IR (KBr): 3417, broad (OH), 2928, 1692 (C=0) cm4.MS: m/e (rel.intensity) 252 (Mt 5), 224 (2), 125 (44), 113 (26), 112 (51), 95 (38), 85(30), 84 (79), 83 (51), 81(39), 79 (25), 71(44), 69 (69), 67 (32), 58 (33), 55 (100).Calculated mass: 252.2089, found: 252.2087.Anal. calcd for C16H2802: C, 76.14; H, 11.18. found: C, 76.00; H, 11.05.217For photoproducts 15c1 and 15c2 the stereochemistry at the ring junction wasconfirmed by X-ray crystallographic analysis.Photolysis of Cycloheptadecane-1,10-dione (16)Solid state irradiation:Diketone 16 was preparatively photolyzed in the solid state using the proceduredescribed in the general experimental section. The reaction mixture on GLC (DB 17,195°C) showed three major peaks at RTs 5.19, 9.28 and 10.46 min. Products werepurified by silica gel column chromatography (Et0Ac:petroleum ether (35-60°C) = 3:97to 12:88) and characterized by spectral analysis.A mixture of two regioisomers, 16-heptadecene-2,10-dione (16e1) and 16-heptadecene-2,11-dione (16e2) (RT 5.19 min), was eluted with 3.5% (v/v) Et0Ac inpetroleum ether as a white solid (65 mg, 7% yield). Recrystallization fromEt20/petroleum ether gave flakes with mp = 47-48°C. A mixture of trans-cyclobutanolregioisomers, bicyclo[13.2.0]heptadecan-7-one, 15-Hydroxy-(1R*,15S*)-(±) (16t1) andbicyclo[13.2.0Theptadecan-6-one, 15-Hydroxy-(1R*,15S*)-(±) (16t2) (RT 9.28 min), waseluted as an oil with 10% (v/v) Et0Ac in petroleum ether (30 mg, 3.2% yield). A mixtureof cis-cyclobutanol regioisomers, bicyclo[13.2.0]heptadecan-7-one, 15-hydroxy-(1R*,15R*)-(±) (16c1) and bicyclo[13.2.0]heptadecan-6-one, 15-hydroxy-(1R*,15R*)-(±) (16c2) (RT 10.46 min), was eluted as an oil with 12% (v/v) Et0Ac in petroleum ether(35-60°C) (27 mg, 2.9% yield). Attempts made to separate the above regioisomers wereunsuccessful.Irradiation in hexane:Analytical solution state photolysis was carried out using the procedure describedin the general experimental section and monitored by GLC (DB 17, 190°C). As observedin solid state reaction, three major peaks were observed at RTs 5.99, 9.20 and 10.36 min.218Preparative scale irradiation was not performed but the products observed on GLC wereassumed to be the same as the solid state counterparts, based on their GLC retentiontimes.16-heptadecene-2,10-dione (16e1) and 16-heptadecene-2,11-dione (16e2)1H NMR: (C6D6, 400 MHz) 5 5.8-5.6 (2H, m, -CH=CH2), 5.1-4.9 (4H, m,CH=CH2), 2.0 (16H, m, methylenes), 1.7 (6H, two singlets, -CH3), 1.5 (12H, m,methylenes), 1.1 (20H, m, methylenes).13C NMR: (C6D6, 50 MHz) 5 203.4 (0=0), 201.0 (C=0), 139.0, 138.7 (2 -fH=CH2),114.7 and 114.6 (2 -CH=fH2), 43.31 (CH2), 43.28 (CH2), 42.6 (CH2), 42.4 (CH2),33.92 (CH2), 33.87 (CH2), 29.62 (CH2), 29.60 (CH2), 29.5 (CH2), 29.4 (CH2), 29.3 and29.2 (2 -CH3), 29.01 (CH2), 28.98 (CH2), 29.8 (CH2), 24.0 (CH2), 23.9 (CH2), 23.89(CH2), 23.87 (CH2), 23.5 (CH2).JR (KBr): 3081, 2932, 1704 (C=0), 1644 cm4.MS: mie (rel.intensity) 266 (M+, 8), 198 (42), 183 (34), 141 (40,140 (37), 128 (30), 127(35), 126 (53), 123 (44), 111 (40), 109 (25), 98 (66), 97 (49), 95 (34), 85 (34), 84 (43),83 (65), 82 (30), 81(44), 71(61), 69 (48), 68 (45), 67 (43), 59 (31), 58 (50), 57 (34), 56(28), 55 (90), 43 (100), 40 (69), 38 (33).Calculated mass: 266.2247, found: 266.2251.Anal. calcd for C17H3002: C, 76.64; H, 11.35. found:C, 76.60; H, 11.45.bicyclo[13.2.0]heptadecan-7-one, 15-Hydroxy-(1R*,15S*)-(±) (16t1) and bicyclo[13.2.0]heptadecan-6-one, 15-Hydroxy-(1R*,15S*)-(±) (16t2)13C NMR: (C6D6, 75 MHz) 5 210.9 and 210.4 (2 C=0), 77.6 and 77.5(2 f-OH), 42.8(methine), 42.0 (CH2), 41.91 (CH2), 41.86 (CH2), 41.7 (CH2), 40.6 (methine), 41.4(CH2), 41.3 (CH2), 34.53 (CH2), 34.49 (CH2), 29.8 (CH2), 29.5 (CH2), 28.4 (CH2), 28.2219(CH2), 28.1 (CH2), 27.8 (CH2), 27.3 (CH2), 27.1 (CH2), 26.9 (CH2), 24.3 (CH2), 23.6(CH2), 23.4 (CH2), 23.3 (CH2), 22.9 (CH2), 22.8 (CH2), 21.6 (CH2), 21.2 (CH2).IR (neat) 3600-3300 (OH), 2933, 1713 (C=0) cm-1.MS: ink (rel.intensity) 266 (M+, 5), 238 (3), 98 (58), 97 (37), 84 (25), 83 (50), 81(29),71(39), 69 (35), 67 (32), 58 (34), 57 (30), 55 (100), 43 (81), 41(70).Calated mass: 266.2247, found: 266.2242.bicyclo[13.2.0]heptadecan-7-one, 15-hydroxy-(1R*,15R*)-W (15c1) and bicyclo[13.2.0]heptadecan-6-one, 15-hydroxy-(1R*,15R*)-(±) (15c2)13C NMR: (C6D6, 75 MHz) 5 210.4 and 209.8 (2 CO), 77.0 and 76.8 (2 c-OH), 50.0and 49.8 (methine), 41.7 (CH2), 41.5 (CH2), 41.3 (CH2), 40.7 (CH2), 34.8 (CH2), 34.51(CH2), 34.47 (CH2), 34.0 (CH2), 30.7 (CH2), 30.3 (CH2), 28.5 (CH2), 28.4 (CH2), 28.0(CH2), 27.8 (CH2), 27.7 (CH2), 27.4 (CH2), 27.3 (CH2), 27.1 (CH2), 27.0 (CH2), 26.4(CH2), 24.1 (CH2), 23.3 (CH2), 22.7 (CH2), 22.4 (CH2), 22.1 (CH2), 21.8 (CH2), 19.2(CH2), 19.0 (CH2).IR (KBr): 3600-3300 (OH), 2941, 1708 (C=0) cm4.MS: mie (rel.intensity) 266 (M+, 10), 238 (4), 140 (28), 127 (26), 126 (41), 125 (39),123 (29), 122 (26), 112 (37), 111 (50), 109 (35), 108 (28), 107 (28), 99 (25), 98 (75), 97(61), 96 (28), 95 (47), 94 (25), 93 (31), 85 (36), 84 (53), 83 (72), 82 (39), 81(55), 80(33), 79 (38), 71(59), 70 (29), 69 (58), 68 (37), 67 (53), 58 (54), 57 (53), 56 (27), 55(100), 53 (27), 43 (91), 42 (35), 40 (75), 38 (29).Calculated mass: 266.2247, found: 266.2254.2206.2.4. Photochemistry of Keto-alcohols.Photolysis of 9-hydroxy-cyclohexadecan-1-one (29):Analytical solution and solid state photolyses of keto-alcohol 29 were explored atroom temperature. In both media, irradiation gave five new peaks on GLC (DB 17,190°C), at RT's 4.5, 8.7, 8.8, 9.2 and 9.5 min.Preparative scale irradiations were canied out, but several attempts to purify thephotoproducts by conventional column chromatography were unsuccessful. The peaks onGLC were identified to a certain extent, as described in Chapter III.Photolysis of 10-hydroxy-cyclooctadecan-1-one (30)Analytical solution and solid state irradiations were performed. Irradiation gavethree new peaks on GLC (DB 17, 205°C) at RT's 5.0, 9.1 and 10.2 min in both media. Asin the case for keto alcohol 29, photoproducts could not be separated by preparative scalephotolysis. However, the photoproducts were identified using the authentic samples asdescribed for keto-alcohol 29 (see Chapter III for details).6.2.5. Photochemistry of Tetramethylated diketones.Photolysis of Tetramethylcyclohexadecane-1,9-dione-(2R*,8S * , 10R* ,16S *) (31).Solid state irradiation :Preparative solid state photolysis of diketone 31 (200 mg) was carried out usingthe procedure described in the general experimental section. GLC analysis (DB 17,190°C) indicated the development of single major product at RT 12.3 min with traces ofother minor products. Photolysis was stopped after 30% total conversion to products andthe reaction mixture was subjected to HPLC (preparative column, flow rate = 5 ml min 1,Et0Ac:hexane = 2:98). The major photoproduct (RT 45 min - HPLC) was eluded as a221white solid (48 mg, 24%) and was later identified as a diastereomer of 31,tetramethylcyclohexadecane-1,9-one-(2R*,8R*,10R*,16S*) (31a). mp = 85-86 °C.Irradiation in hexane :Diketone 31 (300 mg) was preparatively photolyzed using the procedure describedfor diketone 7. On GLC analysis development of two major peaks (RT's 12.3, 13.1 min)and a minor peak (RT 10.8 min) with traces of several other peaks were observed. After30% total conversion to products, the reaction mixture was subjected to HPLC. Only theproduct at RT 10.8 min was purified as a white semi-solid 31b (8 mg, 2.7% yield), but thetwo major products were eluted together with other impurities. From mass, infrared and13C NMR spectral analysis, revealed compound 31b was identified as a diastereoisomerof the starting material with high symmetry (four equivalent methyl and methine groups),but the stereochemistry of the molecule has not been fully determined. The compoundobserved at RT 12.3 min was assumed to be the solid state product 31a based on its GLCretention time.Analytical irradiation:Solution (hexane) and solid state photolyses were performed as described in thegeneral experimental section. Irradiation of the solid for prolonged periods indicated thedevelopment of four major peaks at RT's 10.8, 12.3, 13.1 and 13.3 min. After 60 hrs ofirradiation the four products along with the starting material 31 (RT 11.3 min) attained aphotostationary state. Similar photostationary state was observed in solution after 70 hrsof photolysis, with the absence of peak at RT 13.3 min. The amount of photoproducts (inpercentage) at the stationary state with their corresponding retention times are givenbelow.solid : RTs 10.8 (12%), 11.3 (6%), 12.3 (67%), 13.1 (4%), 13.3(11%).hexane : RT's 10.8 (3%), 11.3 (60%), 12.3 (20%), 13.1 (17%).222Tetramethylcyclohexadecane-1,9-dione-(2R*,8R*,10R*,16S*) (31a)13C NMR: (C6D6, 100 MHz) 5 216.0 and 215.9 (2 C=0), 46.2 , 45.5 , 45.2 , 42.2(4-CH-CH3), 33.4 (CH2), 33.1 (CH2), 32.9 (CH2), 29.2 (CH2), 29.1 (CH2), 27.6 (CH2),27.19 (CH2), 27.16 (CH2), 26.7 (CH2), 17.9 , 17.8 , 17.0 , 16.5 (4 -CH-H3).IR (neat): 2927, 1703 (C=0) cm-1.MS: rule (rel.intensity) 308 (Mt, 30), 223 (29), 154 (25), 125 (26), 112 (67), 97 (41), 86(96), 83 (30), 69 (54), 57 (25), 55 (100), 43 (27), 41(68).Calculated mass: 308.2717, found: 308.2715.Compound (31b)13C NMR: (C6D6, 75 MHz) 5 216.48 (C=0), 45.57 (-,CH-CH3), 32.57 (CH2), 28.93(CH2), 26.76 (CH2), 16.5 (-CH-H3).IR (neat): 2927, 1703 (C=0) cm-1.MS: m/e (relintensity) 308 (M+, 32), 223 (45), 195 (19), 155 (22), 154 (25), 153 (31),125 (43), 112 (75), 111 (22), 99(30), 98(22), 97(65), 96(25), 95 (34), 86(93), 85 (42),83 (57), 81(31), 71(47), 69 (100), 57 (43), 56 (28), 55 (76).Calculated mass: 308.2717, found: 308.2711.Photolysis of Tetramethylcyclotetracosane-1,13-dione-(2R*,12S*, 14R*,24S*) (32)Preparative scale solid state irradiation of diketone 32 (200 mg) was carried outusing the procedure described in the general experimental section. Reaction progress wasmonitored on HPLC (analytical column, flow rate = 0.5 ml min-1, Et0Ac:hexane = 2:98)using the UV detector (X=280 nm). Development of one major peak (RT 14.4 min) withtraces of several peaks was observed. After 30% conversion to products, the reactionmixture was subjected to HPLC (preparative column, Et0Ac:hexane, 2:98, flow rate5.0 mL min-1). The major product was isolated (RT 23.0 min) as a white solid (44 mg,22322%) and was later identified as toramethylcyclotetracosane-1,13-dione-(2R*, 12R*,14R*, 24S*) (32a), mp = 56-58°C.Irradiation in hexane:Analytical solution reaction of diketone 32 was carried out as described in thegeneral experimental section. A reaction identical to that occurring in the solid state wasobserved on HPLC (analytical column). A single major product observed was assumed tobe 32a, based on it's HPLC retention time.Tetramethylcyclotetracosane-1,9-dione-(2R*,12R*,14R*,24S*) (32a)13C NMR: (C6D6, 75 MHz) 8 216.2 and 216.1 (2 C=0), 45.5, 45.4, 44.3, 43.9(4-fH-CH3), 33.7 (CH2), 33.6 (CH2), 33.5 (CH2), 32.0 (CH2), 30.2 (CH2), 30.1 (CH2),29.9 (CH2), 29.5 (CH2), 27.6 (CH2), 27.5 (CH2), 23.0 (CH2), 17.4, 17.2, 17.0, 14.4 (4-CH-H3).IR (neat) 2924, 1701 (C=0) cm-1.MS: mie (rel.intensity) 420 (Mt, 60), 335 (95), 97 (47), 86 (100), 83 (52), 71(33), 69(80), 57 (64), 56 (28), 55 (87), 43 (42), 41(41).Calculated mass: 420.3959, found: 420.3959.Anal. calcd for C28115202: C, 79.94; H, 12.46. found:C, 79.94; H, 12.56.63. Quantum Yield Studies.Internal standards and GC detector responses:Quantum yields were measured for the formation of photoproducts from sixteen(9), eighteen (10) and twenty (12) membered diketones. The straight chain alkanesn-tricosane, n-docosane and n-tetracosane received from Aldrich Chemical Co were224purified by several recrystallizations from Et0H/Et20 solvent system and used as internalstandards.All samples were analyzed by using gas chromatographs having flame ionizationdetectors. The detector responses of the photoproducts with respect to the photoinactiveinternal standards were measured prior to the photolysis and from these studies the exactnumber of moles of photoproducts formed during the reaction were calculated byanalyzing the reaction mixture with a known amount of internal standard.In order to determine the GLC detector response, a solution containing knownamounts of a photoproduct and an appropriate internal standard in hexane was injectedinto the GLC and the ratio of the area under the peaks was compared with the actual ratioof the photoproduct and the internal standard. At least five chromatographic analyseswere made for each sample.The following three solutions (table XVIII) containing diketones and internalstandards were prepared in hexane using known procedures, where the diketoneconcentrations were chosen in such away that the solutions are opaque to 313 nm line ofthe radiation.The GLC detector response of acetophenone with respect to the internal standardn-tetradecane was also determined in order to evaluate the number of moles ofacetophenone formed in the valerophenone actinometry. Finally the number of quanta ofphotons absorbed during the reaction was calculated using the known quantum yield(4)=0.3) of acetophenone formation from 0.1 M valerophenone in benzene (X= 313 nm).A solution containing tetradecane (1 mg mL-1) and valerophenone (0.1 M) inbenzene was used as the actinometer. Benzene was used after being freed from thiopheneby a procedure described in the literature.222Apparatus :A merry-go-round apparatus immersed hi a large water bath was used to performall irradiations.224 The temperature of the apparatus was maintained at 21 ± 2 °C by225circulating water through the water bath. A quartz immersion well with a 450 W mediumpressure mercury lamp was placed in the middle of the apparatus. The 313 nm line of theradiation from the lamp was isolated by circulating a solution of 2x10-3 M K2Cr04containing 5% (w/w) K2CO3 through the immersion well and by placing 7-54 Corningfilters in the filter holders.Table XVIII: Internal standards.Solution Diketone(ringsize)concentration(M)Internal standard concentration(M)1 9 (16) 1.2x10-1 tricosane 4.1x10-32 10 (18) 9.5x10-2 docosane 2.6x10-33 12 (22) 1.4x104 tetracosane 3.9x10-3Irradiation of the samples :The following procedure for diketone 9 is typical. Three Pyrex test tubes (100x13mm), each containing 3 mL aliquots of solution 1 were degassed by three freeze-pump-thaw cycles and secured with a stopper. These three tubes were placed in the merry-go-round apparatus and the irradiation was performed using the 313 nm line of the 450Wmedium pressure lamp. A parallel irradiation of two valerophenone actinometers, eachcontaining 3 mL aliqots of valerophenone (0.1 M) and tetradecane (1 mg mL-1) were alsoperformed. The percentage conversion of the valerophenone and the diketones was keptbelow 5%. The total duration of the photolysis was 12 hr, but altogether four sets (twotubes in each set) of actinometers were used one after the other. At the end, each samplewas analyzed on GLC at least three times. The peak area ratios of the photoproducts withrespect to the internal standards were calculated and the statistical average was taken.226The relative detector responses of the internal standard and the photoproducts studied wasused to calculate the quantum yield. The accuracy in this measurement is approximatelyestimated to be ± 15%.6.4. Quenching Studies.To calculate the product ratios formed through singlet excited states, quenchingstudies of diketone 9 were carried out in hexane using 2,3-dimethy1-1,3-butadiene asquencher. A 25 mL stock solution of 10-1M diketone 9 and 10-1M, 1M and 2M2,3-dimethy1-1,3-butadiene were prepared in hexane using volumetric flasks. These stocksolutions were used to make the following 25 rnL solutions:1) 10-2M diketone in hexane.2) 10-2M diketone + 10-2M^quencher.3) 10-2M diketone + 10-1M^quencher.4) 10-2M diketone + 5x10-1M quencher.5) 10-2M diketone + 9x10-1M quencher.6) 10-2M diketone + 12x10-1M quencher.7) 10-2M diketone + 15x10-1M quencher.8) 10-2M diketone + 18x10-1M quencher.Analytical photolysis was carried out for each solution as described in the generalexperimental section and the product ratios at 0% conversion were calculated. Finally, theproduct ratios (at 0% conversion) were plotted versus quencher concentration to obtainthe singlet product ratios from the plateau of the graph.2276.5. Computational Generation of Diketone Geometries.Macromodel V3. 1X, an interactive molecular modeling software system on aSilicon Graphics 4D (three dimensional operation) work station, was used to generate thepossible low energy conformations of diketones. Steric energies were calculated usingAllinger's molecular mechanics (MM2) programme.225 To generate the low energyconformations of cyclic compounds, a crude molecular geometry supplied by the chemistis subjected to Allinger's energy calculation program (MM2), where the atoms arerepeatedly moved towards positions of lower energy, ultimately to produce a stableconformation. However, the crude starting coordinates will determine to some extent theresultant stable conformation. To find, therefore, all the low energy conformations,including the global minimum, a number of initial geometries must be supplied, and theirenergies must be minimized. With medium and large rings, since they are very flexible, itis quite difficult to produce all starting geometries manually. To solve this problem, W.C.Still has written a program called "Monte Carlo Multiple-Minimum",226 (Figure 86) arandom variational conformational search.This program operates in the following manner. Initially a crude moleculargeometry is drawn on the terminal screen, and this conformation is then minimized interms of energy to a nearby minimum energy conformer. For this optimized conformation,a bond (chosen by the chemist) which is located far from the presence of any functionalgroup is broken. At this point the computer regards the molecule as an acyclic chain. Theprogram then attempts to join the two ends of the chain by a random variation of selectedtorsional angles based on the specified transannular contacts, the closure bond distance,the closure bond angles and the torsional angles, which in turn may be varied according tothe precision required.Constraint test 1 is used to eliminate energy-minimized structures, both thosewhose energies lie outside the selected energetic upper limit relative to the instant globalminimum (usually < 25 kJ mo1-1 above the instant global minimum), and those whosesRecover previoustarting geometry228inter-atomic distances or torsion angles do not match the explicit distance or torsionconstraints provided by the user.Begin with RandomInitial StructureDone.Order structures by energyand output to fileFigure 86: The flow diagram showing the "Monte Carlo Multiple-Minimum"conformational search.229Constraint test 2 eliminates starting geometries that have poor ring-closurecharacteristics, high-energy non-bonded contacts and or energies lying outside the selectedupper limit (usually 100 kJ mol-1 above the instant global minimum).Conformations that pass constraint test 2 are subjected to Allinger's MM2program. A minimized conformation which passes constraint test 1 would be comparedwith the minima found during previous conformational search steps and would be eitherrejected as a duplicate conformation or stored as new. One such cycle is known as theMonte Carlo step (MC).230REFERENCES:1. Canuto, V. M.; Levine, J. S.; Augustson, T. R.; Imhoff, C. L.; Giampapa, M. S.Nature (London). 1983, 305 , 281.2. Cloud, P. Am. J. Sci. 1972, 272, 537.3. Margulis, L.; Walker, J. C. G.; Rambler, M. Nature (London). 1976, 264, 620.4. Blake, A. J.; Carver, J. H. J. Atoms. Sci. 1977, 34, 720.5. Levine, J. S.; Hays, P. B.; Walker, J. C. G. Icarus. 1979, 39, 295.6. Gavezzoti, A.; Simmoneta, M. Chem. Rev. 1982, 82, 1.7. Wohler, F. Pogg. Ann. 1828, 12, 253.8. Trommsdorff, H. Ann. Chem. Phar. 1834, 11, 190.9. Markwald, W. Z. Phys. Chem. 1899, 30, 140.10. (a) Ciamician, G.; Silber, P. Chem. Ber. 1901, 34, 2040. (b) Ciamician, G.;Silber, P. Ber. Dtsch. Chem. Ges. 1907, 34, 2040.11. Stobbe, H.; Steinberger, F.K. Chem. Ber. 1922, 55, 2225.12. De Jong, A. W. K. Chem. Ber. 1923, 56, 818.13. Senier, A.; Shepheard, F. G. J. Chem. Soc. 1909, 95, 1943.14. Scheffer, J. R. Acc. Chem. Res. 1980, 13, 283.15. Matsuura, T.; Sata, Y.; Ogura, K. Tetrahedron Lett. 1968, 4627.16. Ariel, S.; Askari, S.; Scheffer, J. R.; Trotter, J. J. Org . Chem. 1989, 54, 4324.17. Kohlshuter, Z. All g. Chem. 1918, 105, 121.18. Schmidt, G. M. G. Reactivity of the Photoexcited Organic Molecules;Interscience: New York, 1967; p 227.19. Cohen, M. D.; Schmidt, G. M. J. J. Chem. Soc. 1967, 239.20. Liebermann, C. Chem. Ber. 1889, 22, 124 and 782.21. Bernstein, H. I.; Quimby, W. C. J. Am. Chem. Soc. 1943, 65, 1845.22. Cohen, M. D.; Schmidt, G. M. J. J. Chem. Soc. 1964, 1996.23. Schmidt, G. M. G. Pure. App!. Chem. 1971, 27, 647.23124. Cohen, M. D.; Green, B, S. Chem. Ber. 1973, 9, 490 and 517.25. Cohen, M. D.; Schmidt, G. M. J.; Sonntag, F. I. J. Chem. Soc. 1964, 2000.26. Schmidt, G. M. J. Solid State Photochemistry; Ginsburg, D., Ed.;VerlagChemie:New York, 1976.27. Sadeh, T.; Schmidt, G. M. J. J. Am. Chem. Soc. 1962, 84, 3970.28. Lahav, M.; Schmidt, G. M. J. J. Chem. Soc. B 1967, 312.29. Green, B. S.; Lahav, M.; Schmidt, G. M. J. J. Chem. Soc. B 1971, 1552.30. Ramasubbu, N.; Gnanaguru, K.; Venkatesan, K.; Ramamurthy, V.Can. J. Chem. 1982,50, 2337.31. Bhadbhade, M. M.; Murthy, G. S.; Venkatesan, K.; Ramamurthy, V.Chem. Phys. Lett. 1984, 109, 259.32. (a) Gnanaguru, K.; Murthy, G. S.; Venkatesan, K.; Ramamurthy, V.Chem. Phys Lett. 1984, 109, 255. (b) Ramasubbu, Gnanaguru, K.;Venkatesan, K.; Ramamurthy, V. J. Org . Chem. 1985, 50, 2337.33. Gnanaguru, K.; Ramasubbu, N.; Venkatesan, K.; Ramamurthy, V. J. Photochem.1984, 27, 355.34. Ramasubbu, N.; Guru Row, T. N.; Venkatesan, K.; Ramamurthy, V.; Rao, C. N. R.J. Chem. Soc., Chem. Commun. 1982, 178.35. (a) Thomas, J. M. Nature (London) 1981, 289, 633. (b) Nakanishi, H.;Jones, W.; Thomas, J. M.; Hursthouse, M. B.; Motevalli, M. J. Phys. Chem.1981, 85, 3636. (c) Jones, W.; Ramdas, S.; Theocharis, C. R.; Thomas, J. M.;Thomas, N.W . J. Phys. Chem. 1981, 85, 2594.36. (a) Nakanishi, H.; Jones, W.; Thomas, J. M. Chem. Phys. Lett. 1980, 71, 44.(b) Nakanishi, H.; Jones, W.; Thomas, J. M.; Hursthouse, M. B.; Motevalli, M.J. Chem. Soc., Chem. Commun. 1980, 611. (c) Nakanishi, H.; Jones, W.;Theocharis, C. R.; Thomas, J. M. J .Chern. Soc., Chem. Commun. 1980, 610.37. Ramamurthy, V.; Venkatesan, K. Chem. Rev. 1987, 87, 433-481.23238. Craig, D. P.; Sarti-Fantoni, P. J. Chem. Soc., Chen?. Commun. 1966, 762.39. Bart, J. C.; Schmidt, G. M. J. Isr. J. Chem. 1971, 9, 429.40. Heller, E.; Schmidt, G. M. J. Isr. J. Chem. 1971, 9, 449.41. Thomas, J. M.; Williams, J. 0. J. Chem. Soc., Chem. Commun. 1967, 432.42. Murthy, G. C.; Arjunan, P.; Venkatesan, K.; Ramamurthy, V. Tetrahedron.1987,43, 1225.43. Cohen, M. D. Angew.Chem., Mt. Ed. Engl. 1975, 14, 386.44. (a) McBride, J. M. Acc. Chem. Res. 1983, 16, 304-312. (b) McBride, J. M.;Segmuller, B. E.; Hollingsworth, M. D.; Mills, D. E.; Weber, B. A. Science.1986, 234,830-835. (c) McBride, J.M.; Walter, D. W. J. Am. Chem. Soc.1981, 103, 7069. (d) McBride,J. M.; Walter, D. W. J. Am. Chem. Soc.1981, 103, 7074. (e) Karch, N. J.; Koh, E. T.; Whitsel, B. L.; Mc Bride, J. M.J. Am. Chem. Soc. 1975, 97, 6729.(f) Hollingsworth, M. D.; Mc Bride, J. M. J. Am. Chem. Soc. 1985, 107, 1792.45. (a) Gavezzotti, A.; Simonetta. In Organic Solid State Chemistry; Desiraju, G. R.,Ed.;Elsevier: Amsterdam, 1987; pp 391. (b) Destro, R.; Gavezzotti, A.In Structure and Properties of Molecular Crystals; Pienot, M., Ed.; Elsevier:Amsterdam, 1990; pp 161. (c) Gavezzotti, A. J. Am. Chem. Soc. 1983. 105, 5220.(d) Gavezzotti, A. J. Am. Chem. Soc. 1985, 107, 962. (e) Gavezzotti, A.Nouv. . J. Chim. 1982, 6, 443. (f) Gavezzotti, A. Tetrahedron. 1987, 43, 1241.(g) Gavezzotti, A. Acta. Dystallogr. 1987, B43, 559.46. Ariel, S.; Askari, S.; Evans, S. V.; Hwang, C.; Jay, J.; Scheffer, J. R.; Trotter, J.;Walsh, L.; Wong, Y. Tetrahedron. 1987, 43, 1253-1272.47. (a) Kurihara, T.; Uchida, A.; Ohashi, Y.; Sasada, Y.; Ohgo, Y. J. Am. Chem. Soc.1984, 106, 5718. (b) Ohashi, Y.; Yanagi, T.; Kurihara, Y.; Sasada, Y.; Ohgo, Y.J. Am. Chem. Soc. 1982, 104, 6353.48. Ohashi, Y.; Uchida, A.; Sasada, Y.; Ohgo, Y. Acta. Crystallogr. 1988, B44, 538.23349. Dunitz, J. D. X-Ray Analysis and the Structure of Organic Molecules;Cornell University Press: Ithaca, New York, 1979; pp 312-318.50. Ergler, C.; Dorant, K. Chem. Ber. 1895, 28, 2497.51. (a) Rabinovich, D.; Schmidt, G. M. J. J. Chem. Soc. B 1970, 6-10.(b) Jungk,A. E.; Schmidt, G. M. J. J. Chem. Soc. B 1970, 1427-1434.(c) Jungk, A. E.; Luwisch, M.; Pinchas, S.; Schmidt, G. M. J. Isr. J. Chem1977, 16, 308-310. (d) Curtin, D. Y.; Engelman, J. H. J. Org. Chem.1972, 37 , 3439-3443.52. Cohen, M. D. J. Chem. Soc. B 1968, 373-376.53. Matsura, T.; Sata, Y.; Ogura, K. Tetrahedron. Lett. 1968, 4627-4630.54. (a) Appel, W. K.; Greenhough, T. J.; Scheffer, J. R.; Trotter, J.; Walsh, L.J. Am. Chem. Soc. 1980, 102, 1158-1160. (b) Appel, W. K.; Greenhough, T. J.;Scheffer, J.R.; Trotter, J. J. Am. Chem. Soc. 1980, 102, 1160-1161.(c) Jiang, Z. Q.; Scheffer, J. R.; Secco, A. S.; Trotter, J. Tetrahedron. Lett.1981, 891-894. (d) Appel, W. K.; Jiang, Z. Q.; Scheffer, J. R.; Walsh, L.J. Am. Chem. Soc. 1983, 105, 5354- 5363. (e) Scheffer, J. R.; Trotter, J.;Appel, W. K.; Greenhough, T. J.; Jiang, Z. Q.; Secco, A. S.; Walsh, L.Mol. Cryst. Liq. Cryst. 1983, 93 ,1-15. (f) Ariel, S.; Askari, S.; Scheffer, J. R.;Trotter, J. J. Org . Chem. 1989, 54, 4324. (g) Ariel, S.; Askari, S.;Scheffer, J. R.; Trotter, J.; Walsh, L. J. Am. Chem. Soc. 1984, 106, 5726-5728.55. (a) Scheffer, J. R.; Bhandari, K. S.; Gayler, R. E.; Wostradowski, R. A.J. Am. Chem. Soc. 1975, 97, 2178-2189. (b) Scheffer, J. R.; Jennings, B. M.;Louwrens, J. P. J. Am. Chem. Soc. 1976, 98, 7040 (c) Scheffer, J. R.;Dzakapasu, A. A. J. Am. Chem. Soc. 1978, 100, 2163-2173. (d) Ariel, S.;Evans, S.; Hwang, C.; Jay, J.; Scheffer, J. R.; Trotter, J.; Wong, Y. F.Tetrahedron. Lett. 1985, 965-968. (e) Ariel, S.; Askari, S.; Scheffer, J. R.;Trotter, J. Tetrahedron. Lett. 1986, 27, 783-786. (f) Ariel, S.; Askari, S.;234Scheffer, J. R.; Trotter, J.; Wireko, F. J. Am. Chem. Soc. 1987, 109, 4623.(g) Ariel, S.; Askari, S.; Scheffer, J. R.; Trotter, J.; Wireko, F. Acta. Crystallogr.1987, B43, 532.56. Appel, W. K.; Greenhough, T. J.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc.1979, 101, 213-215.57. (a) Ariel, S.; Evans, S.; Garcia-Garibay, M.; Harkness, B. R.; Omkaram, N.;Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc. 1988, 110, 5591.(b) Scheffer, J. R.; Trotter, J. Chem. Rev. Mt. 1988, 9, 271. (c) Ariel, S.;Garcia-Gaiibay, M.; Scheffer, J. R.; Trotter, J. Acta. Crystallogr. 1989,B45, 153. (d) Evans, S.; Omkaram, N.; Scheffer, J. R.; Trotter, J. Tetrahedron.Lett. 1986, 27, 1419. (e) Evans, S. V; Garcia-Garibay, M.; Omkaram, N.;Scheffer, J. R.; Trotter, J.; Wireko, F. J. Am. Chem. Soc. 1986, 108, 5648.(f) Ariel, S.; Evans, S. V.; Omkaram, N.; Scheffer, J.R.; Trotter, J. Mol. Cryst. Liq.Cryst. 1986, 134, 169.58. (a) Garcia-Gaiibay, M.; Scheffer, J. R.; Trotter, J.; Wireko, F. J. Am. Chem. Soc.1989, 111, 4985. (b) Garcia-Garibay, M.; Scheffer, J. R.; Trotter, J.; Wireko, F.Tetrahedron. Lett. 1987, 28, 4789. (c) Chen, J.; Garcia-Garibay, M.;Scheffer, J. R.; Trotter, J.; Wireko, F. Tetrahedron Lett. 1989, 30, 6125.(d) Garcia-Garibay, M.; Scheffer, J. R.; Trotter, J.; Wireko, F. Tetrahedron.Lett. 1988, 29, 2042. (e) Garcia-Garibay, M.; Scheffer, J. R.; Watson, D. G.J. Chem. Soc., Chem. Commun. 1989,600. (f) Pokkuluri, P. R.; Scheffer, J. R.;Trotter, J.; Wireko, F. Tetrahedron. Lett. 1989, 30, 1601. (g) Garcia-Garibay, M.;Scheffer, J. R.; Trotter, J.; Wireko, F. Tetrahedron. Lett. 1987 28, 1741.(h) Garcia-Garibay, M.; Scheffer, J.R.; Trotter, J.; Wireko, F. J. Am. Chem. Soc.1989, 111, 4985. (i) Poldailuri, P. R.; Scheffer, J.R.; Trotter, J. J. Am. Chem. Soc.1990, 112, 3676.59. Wagner, P. J. Acc. Chem. Res. 1971, 4, 168.23560. Wagner, P. J.; Park, B. -S. In Organic Photochemistry; Padwa, A., Ed.; MarcelDekker New York, 1991; Vol. 11, Chapter 4.61. Yang, N. C.; Yang, D. H. J. Am. Chem. Soc. 1958, 80, 2913.62. (a) Norrish, R. G. W. Trans. Faraday Soc. 1937, 33, 1521. (b) Saltmarsh, 0. D.;Norrish, R. G. W. J. Chem. Soc. 1935, 455.63. a) Henne, A.; Fischer, H. Angew.Chem., Mt. Ed. Engl. 1976, 15, 435.b) Wagner, P. J. J. Am. Chem. Soc. 1967, 89, 5898.64. Wagner, P. J.; Kelso, P. A.; Kemppainen, Zepp. R. G. J. Am. Chem. Soc.1972, 94, 7500-7506.65. Dorigo, A. E.; Houk, K. N. J. Org . Chem. 1988, 53, 1650.66. Dorigo, A. E.; McCarrick, Loncharich, R. J.; Houk, K. N. J. Am. Chem. Soc.1990, 112, 7508.67. (a) Pople, J. A.; Gordon, J. J. Am. Chem. Soc. 1967, 89, 4253-4261.(b) Winnik, M.A. Acc. Chem. Res. 1977, 10, 173-179. (c) Dewar, M. J. S.;Doubleday, C. J. Am. Chem. Soc .1978, 100, 4935-4941. (d) Morrison, H.;Miller, A.; Pandey, B.; Severance, D.; Strommen, R.; Bigot, B. Pure App!. Chem.1982, 54, 1723-1732.68. (a) Djerassi, R. Pure App!. Chem. 1964, 9, 159-179. (b) Djerassi, C.;Williams, D. H.; von Muntzenbecher, G.; Budzikiewicz, H. J. Am. Chem. Soc.1965, 87, 817-826.69. Hewster, K.; Kalvoda, J. Angew. Chem., Int. Ed. Eng. 1964, 3, 525.70. Scheffer, J. R.; Garcia-Gariby, M.; Omkaram, N. Org. Photochem. 1987,8, 249.71. Bondi, A. J. Phys. Chem. 1964, 68, 441-451.72. Turro, N. J.; Weiss, D. S. J. Am. Chem. Soc. 1968, 90, 2185.73. Edward, J. T. J. Chem. Educ. 1970, 47, 261-270.23674. Sugiyama, N.; Nishio, T.; Yamada, K.; Aoyama. Bull.Chern. Soc. Jpn.1970, 43,1879.75. Chang, H. C.; Popovitz-Biro, R.; Lahav, M.; Leiserowitz, L. J. Am. Chem. Soc.1943, 65, 1845-1846.76. Wagner, P. J. Top. Curr. Chem. 1976, 66, 1.77. Colpa, J. P.; Stehlik, D. J. Chem. Phys. 1983, 81, 16378. TUITO, N. J. Modern Molecular Photochemistry; Benjamin Cummings:Menlo Park, California, 1972; Chapter 10.79. Scheffer, J. R. In Organic Solid State Chemistry; Desiraju, G. R., Ed.; Elsevier:Amsterdam, 1987; Chapter 1.80. Ciamician, G.; Silber, P. Ber. Dtsch. Chem. Ges. 1907, 40, 2415.81. Bamford, C. H.; Norrish, R. G. W. J. Chem. Soc. 1935, 1504.82. a) Saltmarsh, 0. D.; Norrish, R. G. W. J. Chem. Soc. 1935, 455. b) Dalton, J. C.,J. Am. Chem. Soc. 1943, 65, 1845-1846.83. (a) Dalton, J. C.; Turro, N. J. Annu. Rev. Phys. Chem. 1970, 21, 499.(b) Turro, N. J.; Dalton, J. C.; Dawes, K.; Farrington, G.; Hautala, R.; Morton, D.;Niemczyk, M.; Shore, N. Acc. Chem. Res. 1972, 5, 92.84. Furth, B.; Jost, P.; Sabbah, S.; Kossanyi, J. Nouveau J. Chim. 1979, 3 , 199.85. (a) Mitscherlich, E. Ann. Chim. Phys. 1822, 19, 350. (b) Mitscherlich, E.Ann. Chim.Phys. 1823, 24, 264.86. (a) Bernstein, J. In Organic Solid State Chemistry; Desiraju, G. R., Ed.;Elsevier: Amsterdam, 1987; pp 471. (b) Corradini, P. Chim. Ind.1973, 55, 122.87. Dunitz, J. D. Pure Appl. Chem. 1991, 63, 177-185.88) McCrone, W. C. Physics and Chemistry of the Organic Solid State;Fox, D., Ed.; Wiley-Interscience: New York, 1965; Vol 2,Chapter 8.89) Mnyukh, Y. V. Mol. Cryst. Lig. Cryst. 1979, 52, 163-218.23790) Hassel, 0. Tidsskr. Kjemi, Bergves. Metallurgi. 1943, 3, 32.91) Ramsey, O.B. Stereochemistry; Heyden: London, 1981.92) Barton, D. H. R.; Cookson, R. C. Quart. Rev. 1956, 10, 44.93) Eliel, E. L. Stereochemisby of Carbon Compounds; McGraw-Hill:New York, 1962.94) (a) Ruzicka, L.; Stoll, M.; Huyser, H. W.; Boekenooger, H. A. Helv.Chim Acta.1946, 29, 1611. (b) Kobelt, M.; Barman, P.; Prelog, V.; Ruzicka, L.Helv.Chim.Acta. 1949, 32, 356.95) Prelog, V. J. Chem. Soc. 1950,420.96) Huber, E.; Dunitz, J. D.; Venkatesan, K. Proc. Chem. Soc. 1961, 463.97. Mohr, E. J. Prakt. Chem. 1918, 98, 315.98. (a) Dale, J. J. Chem. Soc. 1963, 93. (b) Dale, J. Angew.Chem., Mt. Ed. Engl.1966, 5, 1000.99. (a) Dale, J. J. Chem. Soc., Chem. Comm. 1970, 1340. (b) Growth, P.Acta. Chem. Scand., Ser.A 1979, 33, 203.100. Dunitz, J. D.; Shearer, H. Helv.Chim.Acta. 1960, 43, 18.101. (a) Groth, P. Acta. Chem. Scand., Ser.A 1979, 33, 503. (b) Dehli, J.;Groth, P. Acta. Chem. Scand., Ser.A 1969, 23, 587.102. (a) Dale, J. Pure. Appl.Chem. 1971, 25, 469. (b) Growth, P. Acta. Chem.Scand., Ser.A 1974, 28, 808.103. Alvik, T.; Borgen, G.; Dale, J. Acta. Chem. Scand., Ser.A 1972, 26, 1805.104. Dale, J. Acta. Chem. Scand., Ser.A 1973, 27, 1130.105. Anet, F. A. L.; Cheng, A. K.; Krane, J. J. Am. Chem. Soc. 1973, 14, 7877.106. (a) Growth, P. Acta Chem. Scand., Ser A 1979, 33, 199. (b) Kay, H. F.;Newman, B. A. Acta Crystallogr. 1968, B24, 615.107. Allinger, N. L.; Gorden, B. J.; Newton, M. G.; Lauritsen-Norskov, L.;Profeta, S., Jr. Tetrahedron 1982, 38, 2905.238108. Huckel, W.; Danneel, R.; Schwartz, A.; Gercke, A. Ann. 1929, 474, 121.109. Pappas, J. J,; Keaveney, W. P.; Gancher, E.; Berger, M. Tetrahedron Lett.1966, 36, 4273-4278.110. Alvik, T.; Dale, J. Acta Chem. Scand. 1971, 25, 1153.111. Blomquist, A. T.; Spencer, R. D. J. Am. Chem. Soc. 1948, 70, 30.112. Leonard, N. J.; Schimelpfenig, C. W. J. Org. Chem. 1958, 23 , 1708.113. Ruzicka, L.; Brugger, N.; Seidel, C. F.; Schinz, H. Hely. Chirn. Acta.1928, 11, 496.114. Ruzicka, L.; Stoll, M.; Huyser, H. W.; Boekenoogen, H. A. Hely. Chim.Acta 1930, 13, 1152.115. Wagner, P. J. In Rearrangements in Ground and Excited States;de Mayo, P., Ed.; Academic: New York, 1980; Vol. 3, chapter 20.116. Wagner, P. J. Acc. Chem. Res. 1983, 16, 461.117. Lewis, E. S. Isotopes in Organic Chemistry; Buncel, E.; Lee. C. C., Eds.;Elsevier: Amsterdam, 1976; Vol. 2, p 134.118. Allinger, N. L.; Gorden, B. J.; Profeta, S., Jr. Tetrahedron Lett. 1980, 36, 859.119. Luknitskii, F. I.; Vovsi, B. A. Russ. Chem. Rev. 1969, 38(6), 493.120. Elam, E. U. J. Org . Chem. 1972, 60, 27.121. Sauer, J. C. J. Am. Chem. Soc. 1947, 69, 2444.122. Horner, L.; Spietschka, E.; Gross, A. Ann. Chem. 1951, 17 573.123. March, J. Advance Organic Chemistry, 4th ed.; Wiley-Interscience: New York,1992; Chapter 6.124. Belsky. Tetrahedron. 1976, 28, 771.125. Monson, R. S. J. Heterocyclic Chem. 1976, 13, 893.126. Cordonnier, G.; Sliwa, H. J. Heterocydic.Chem. 1978, 24, 111.127. Piers, E.; Wall, W.; Britton, R. W. J. Am. Chem. Soc . 1971, 25 , 5114.128. House, H. 0.; Kramer, V. J. Org . Chem. 1962, 28, 3362.239129. Mori, T.; Matsui, K.; Nozaki, H. Tetrahedron Lett. 1970, 14, 1175.130. Schulte-Elte, K. H.; Willhalm, B.; Thomas, A. F.; Stoll, M.; Ohloff, G.Hely .Chim. Acta 1971, 54, 1759.131. Burchill, P. J.; Kelso, G.; Power, A. J. Aust. J. Chem. 1976. 29. 2477.132. Encina, M. V.; Lissi, E. A. J. Photochem. 1978, 8, 131.133. Mirbach, M. F.; Mirbach, M. J, Liu, K. C.; TUITO, N. J. J. Photochem.1978, 8, 299.134. Matsui, K.; Mori, T.; Nozaki, H. Bull. Chem. Soc. Jpn. 1971, 44, 3440.135. Barnard, M.; Yang, N. C. Proc. Chem. Soc. 1958, 302.136. Sauers, R. R.; Huang, S. Tetrahedron Lett. 1990, 31, 5709.137. Dewar, M. J. S.; Doubleday, C. J. Am. Chem. Soc. 1978, 100, 4395.138. Wagner, P. J.; Kelso, P. A.; Kemppainen, app. R. G. J. Am. Chem. Soc.1972, 94, 7506.139. Lewis, F. D.; Johnson, R. W.; Kory, D. R. J. Am. Chem. Soc. 1974, 96, 6100.140. Patt, S. L.; Shoolery, J. N. J. Magn. Reson. 1982, 46,535 .141. Silverstein, R. M.; Bassler,G. C.; Morrill, T. C. Spectrometric Identifiationof Organic Compounds, 4th ed.; John Wiley & Sons, Inc.: New York, 1981;p259.142. Herzschuh, R.; Epsch, K. J. Magn. Reson. 1980, 322, 37.143. Dunitz, J. D. and Iberes. J. A. In Perspectives in Structural Chemistry;John Wiley & Sons: New York, 1968; Vol. 2.144. Ariel, S.; Ramamurthy, V.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc.1983, 105, 6959.145. Wagner, P. J. Pure. App!. Chem. i977, 49, 259.146. Scaiano, J. C.; Lissi, E. A.; Encinas, M. V. Rev. Chem. Intermed. 1978,2, 139-195.147. Scaiano, J. C. Acc. Chem. Res. 1982, 15, 252.240148. Scaiano, J. C. Tetrahedron. 1982, 38, 819.149. Wagner, P. J.; Hammond, G. S. J. Am. Chem. Soc. 1965, 87, 4009.150. Dougherty, T. J. J. Am. Chem. Soc. 1965, 87, 4011.151. Salem,L. J. Am. Chem. Soc. 1974, 96, 3486.152. Michl, J. Topics. Curr. Chem. 1974, 46, 1.153. Stephenson, L. M.; Cavigli, P. R.; Parlett, J. L. J. Am. Chem. Soc. 1971,93, 1984.154. Casey, C. P.; Boggs, R. A. J. Am. Chem. Soc. 1972, 94, 6457.155. Yang, N. C.; Elliot, S. P. J. Am. Chem. Soc. 1969, 91, 7550.156. Ware, W. R.; Lee, S. K. J. Chem. Phys. 1968, 49, 217.157. (a) Golden, D. M.; Furuyama, S.; Benson, S. W. Int. J. Chem. Kinet.1969, I, 57. (b) Pitzer, K. S. Discuss. Faraday Soc. 1951, 10, 66.(c) Lide, D. R., Jr.; Mann, D. E. J. Chem. Phys. 1958, 29, 914.(d) Lide, D. R., Jr. J. Chem. Phys. 1958, 29, 1426.158. O'Neal, H. E.; Miller, R. G.; Gunderson, E. J. Am. Chem. Soc. 1974, 96, 3351.159. Encinas, M. V.; Scaiano, J. C. J. Am. Chem. Soc. 1978, 100, 7101.160. Yang, N. C.; Coulson, D. R. J. Am. Chem. Soc. 1966, 88, 4511.161. Kristiansen, P.; Ledaal, T. Tetrahedron Lett. 1971, 2817.162. Furman. I.; Raymond, J.; Catchings, R. M; Weiss, R.G. J. Am. Chem. Soc.1992, 114, 6023.163. Brokman, R. F.; Kearns, D. R. J. Chem .Phys. 1964, 40, 1038.164. Aoyama, H.; Sakamoto, M.; Kuwabara, K.; Yoshida, K.; Omote, Y.J. Am. Chem. Soc. 1983, 105, 1958.165. Yang, N. C.; Elliot, S. P.; Kim, B. J. Am. Chem. Soc. 1969, 91, 7551.166. The conformation was calculated by us using the MM2 force fields.167. Cohen, M. D.; Schmidt, G. M. J.; Flavian, S. J. Chem. Soc. 1964, 2041.168. Ichimura, K.; Watanabe, S. Tetrahedron Lett. 1972, 821.241169. Ichimura, K.; Watanabe, S. Bull.Chern. Soc. Jpn. 1976, 49, 2220.170. (a) Galli, C.; Illuminati, G.; Mandolini, L.; Tamborra, P. J. Am. Chem. Soc.1977, 99, 2591. (b). Galli, C.; Illuminati, G.; Mandolini, L.; Tamborra, P.Acc.Chem. Res. 1981, 14, 95. (c) Benedetti, F.; Stirling, C. J. M.J. Chem. Soc., Perkin Trans. 2 1986, 605.171. Ariel, S.; Ramamurthy, V.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc.1983, 105, 6990.172. Wagner, P. J.; Kemppainen, A. E. J. Am. Chem. Soc. 1968, 90, 5896.173. Hoffman, R.; Swaminathan, S.; O'Dell, B. G.; Gleiter, R. J. Am. Chem. Soc.1970, 92, 7091.174. Nunez, A.; Weiss, R. G. Bol. Soc. Chil. Quim. 1990, 35, 3.175. He, Z.; Weiss, R. G. J. Am. Chem. Soc. 1990, 112, 5535.176. Fleming, I.; Kemp-Jones, A. V.; Long, W. E.; Thomas, E. J. J. Chem. Soc.,Perkin Trans. 2 1976, 7.177. Rawdah, T. N. Tetrahedron. 1991, 47, 8579.178. Rawdah, T. N.; El-Faer, M. Z. Tetrahedron. 1990, 46, 4101.179. (a) Willy, E. W.; Binsch, G.; Eliel, L. E. J. Am. Chem. Soc.1970, 92, 5394. (b) Lipnick, J. Mol. Struct. 1974, 21, 423.180. Allinger, N. A.; Tribble, M. T.; Miller, M. A. Tetrahedron. 1972, 28, 1173.181. Rawdah, T. N. Tetrahedron. 1989, 45, 7405.182. Small, R. D., Jr.; Scaiano, J. C. Chem. Phys. Lett. 1978, 59, 246.183. Boer, F. P.; Shannon, T. W.; McLafferty, F. W. J. Am. Chem. Soc.1968, 90, 7239.184. (a) Byrn, S. R. The Solid State Chemist!), of Drugs; Acadamic Press:New York, 1982. (b) Cohen, M. D.; Schmidt, G. M. J. J. Org . Chem.1964, 1996. (c) Berkovitch-Yellin, Z.; Lahav,M.; Leiserovitz, L. J. Am. Chem. Soc.1974, 96, 918. (d) Cohen, M. D.; Elgavi, A.; Green, B. S.; Ludmer, Z.;242Schmidt, G. M. J. J. Am. Chem. Soc. 1972, 94, 6776. (d) Cohen, R.; Ludmer, Z.;Yakhot, V. Chem. Phys. Lett. 1975, 34, 5679. (e) Warshell, A.; Shakked, Z.J. Am. Chem. Soc. 1975, 97, 5679.185. Dunitz, J. D. In Solid State Photochemistry; Ginsburgh, D., Ed.; VerlagChemie: New York, 1976; p.255.186. Lewis, T. J.; Rettig, S. J.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc.1991, 113, 8180.187. (a) Casal, H. L.; de Mayo, P.; Miranda, J. F.; Sciano, J. C. J. Am. Chem. Soc.1983, 105, 5155.188. (b) Turro, N. J.; Wan, P. Tetrahedron Lett. 1984, 25, 3655. (c) Hrovat,D. A.;Liu, J. H.; Tuiro, N. J.; Weiss, R. G. J. Am. Chem. Soc. 1984, 106, 7033.(d) Zimmermann, R. G.; Liu, J. H.; Weiss, R. G. J. Am. Chem. Soc. 1986,108, 5264. (e) Treanor, R. L.; Weiss, R. G. Tetrahedron. 1987, 43, 1371.(0 Treanor, R. L.; Weiss, R. G.; Nunez. A. Pure. Appl. Chem. 1988, 60, 999.189. (a) Furman. I.; Weiss, R.G. J. Am. Chem. Soc. 1992, 114, 1381. (b) He, Z.;Weiss, R. G. J. Am. Chem. Soc. 1990, 112, 5535.191. Nakanishi, H.; Ueno, K. J. Polym. Sci. 1987, 16, 767.192. (a) All solid state NMR investigations were performed byProf. Colin Fyfe et al and the spectral interpretations were provided bythem. b) Fyfe, C. A. "Solid State NMR for chemists"., C.F.C. Press,Onttario, Canada, 1983.193. Davis, J. H. Biochem. Biophys. Acta 1983, 117, 737.194. (a) Butenandt, A.; Wolff, A. Chem. Ber. 1939, 72, 1121. (b) Wehrli, A,Schaffner, K. Hely. Chem. Acta. 1962, 45, 385.195. (a) Wagner, P. J.; Spoerke, R. W. J. Am. Chem. Soc. 1969, 91, 4437.(b) Dunion, P.; Trumbore, C. N. J. Am. Chem. Soc. 1965, 87, 4211.(c) Srinivasan, R.; Cremer, S. E. J. Am. Chem. Soc. 1965, 87, 1647.243196. Dalton, J. C.; Turro, N. J. Ann. Rev. Phys. Chem. 1970, 21, 499.197. Chapman, 0. L.; Weiss, D. S. Org. Photochem. 1973, 3 , 197.198. (a) Weiss, D. S.; Haslanger, M.; Lawton, R. G. J. Am. Chem. Soc. 1976, 98,1050. (b) Agosta, W. C.; Wolff, S. J. Am. Chem. Soc. 1976, 98, 4182.(c) Yang, N. C.; Chen, R. H. -K. J. Am. Chem. Soc. 1971, 93, 530.199. (a) Coyle, J. D. J. Chem. Soc. B 1971, 1736. (b) Hammond, W. B.; Yeung, T. S.Tetrahedron Lett. 1975, 1169.200. Turro, N. J.; Dalton, J. C.; Dawes, K.; Farrington, G.; Hautala, R.;Morton, D.; Niemczyk, M.; Shore, N. Acc. Chem. Res. 1972, 5, 92.201. Weiss, D. S.; Kochanek, P. M. Tetrahedron Lett. 1977, 9, 763.202. Han, N.; Hwang, K. C.; Lei, X.; Turro, N. J. J. Photochem. Photobiol.,B1991, 61, 35.203. Lei, X.; Zimmt, M.; Doubleday, C., Jr.; Turro, N. J. J. Am. Che. Soc. 1986,108, 2444.204. Weiss, D. S. In Organic Photochemistry; Padwa, A., Ed.; Marcel Dekker:New York, 1981; Vol 5, Chapter 4.205. The dimethykyclododecanones, (R*, 5*)-2,12-cyclododecanone and(R*, S*)-2,12-cyclododecanone were obtained from Prof. L. Weiler'slaboratory.206. (a) Ramamurthy, V. Tetrahedron 1986, 42, 5753. (b) Ramamurthy, V.;Scheffer, J. R.; TU1TO, N. J. Tetrahedron 1987, 43, 1197.(c) Kalyanasundaram, K. Photochemistry in Microheterogeneous Systems;Academic: New York, 1987. Weiss, R. G. Tetrahedron 1988, 44, 3413.(d) Scheffer, J. R.; Trotter, J. Rev. Chem Jnt. 1988, 9,271.(e) Fox, M. A. Top. Curr. Chem. 1987, 142, 71. (f) Anpo, M.; Matsura,T.Photochemistry on Solid Surfaces; Elsevier: Amsterdam,1989.244207. Ramamurthy, V. In Photochemistry in Organized and ConstrainedMedia; Turro, N. J., Garcia-Garibay, M., Eds.; VCH: New York, 1991;Chapter 1. Ramamurthy. V. Ibid.; Chapter 10.208. (a) TUff0, N. J.; Zhang, Z. Tetrahedron Lett. 1989, 30, 3761. (b) Gessner, F.;Olea, A..; Lobaugh, J. H.; Johnston, L.; Scaiano, J. C. J. Org . Chem.1989, 54, 259. (c) Liu, X.; Iu, K. K.; Thomas, J. K. J. Phys. Chem.1989, 93, 4120. (d) Ramamurthy,V.; Caspar, J. V.; Corbin, D. R.; Schyler, B.;Maki,A. H. J. Phys. Chem. 1990, 94, 3391.209. Barrer, R. M. In Inclusion Compounds; Atwood, J. L.; Davies, J. E. D.;Mac Nicol,D. D., Eds.; Academic press: London, 1984; pp 191.210. (a) Meier, W. M.; Olson, D. H. In Atlas of Zeolite Structure Types;Butterworths: Cambridge, 1987. (b) Breck, D. W. Zeolite Molecular Sieves,2nd ed.; Wiley: New York, 1974.211. (a) Bahnemann, D. W.; Monig, J.; Chapman. J. Phys. Chem. 1987,91, 3782. (b) Shiragami, T.; Pac, C.; Yanagida, S. J. Chem. Soc.,Chem. Commun. 1989, 831. (c) Meissenr, D.; Memming, R.; Kastening, B.J. Phys. Chem. 1988, 92, 3476.(d) Ramamurthy, V.; Corbin,D. R.; TUITO, N. J.; Sato, Y. Tetrahedron Lett.1989, 30, 5829.212. Ramamurthy, V.; Corbin, D. R.; Eaton, D. F. J. Org. Chem. 1990, 55, 5269.213. Ramamurthy, V.; Lei, X-G.; TUITO, N. J.; Lewis, T. J.; Scheffer, J. R.Tetrahedron Lett. 1991, 32, 7675.214. (a) Breck, D. W. Zeolite Molecular Sieves; JohnWiley: New York, 1974.(b) Smith, J. V. Chem. Rev. 1987, 88, 149.215. (a) O'Malley, P. J. Chem. Phys. Lett. 1990, 166, 340. (b) Piimet, M.;Garbowski, E.; Mathieu, M. V.; Imelik, B. J. Chem. Soc, Faraday Trans. I1980, 76, 1942. (c) de Menorval, L. C.; Raftery, D.; Liu, S. B.; Takegoshi, K.;245Ryoo, R.; Pines, A. J. Phys. Chem. 1990, 94, 27. (d) Czjek, M.; Vogt, T.;Fuess, H. Angew. Chem. Int. Ed. Engl. 1989, 28, 770. (e) Jobic, H.;Renouprez, A.; Fitch, A. N.; Lauter, H. J.J. Chem. Soc., Faraday Trans. I 1987, 83, 3199. (f) de Mallmann, A.;Barthomeuf, D. J. Phys. Chem. 1989, 93, 5636. (g) Demontis, P.;Yashonath, S.; Klein, M. L. J. Phys. Chem. 1989, 93, 5016.216. (a) Wagner, P. J. J. Am. Chem. Soc. 1967, 89, 5898. (b) Baltrop, J. A.;Coyle, J. D. Tetrahedron Lett. 1968, 3235.217. Ramamurthy, V.; Caspar, V. Mol. Cryst. Liq. Cryst. 1992, 211, 211.218. Lechert, H.; Balser, W. D. J. Phys. Chem. Solids. 1989, 50, 497.219. Ramamurthy, V.; Corbin, D. R. Johnston, L. J. Am. Chem. Soc. 1992,114, 3870.220. Patt, S. L.; Shoolery, J. N. J.Magn. Reson. 1982, 46, 535.221. Still, W. C.; Kahn, M.; Mitra, A. J. Am. Chem. Soc. 1978, 43 , 2923.222. Perrin, D. D.; Armarero, W. L. F.; Perrin, D. R. Purification of laboratorychemicals; Pergamon press: Oxford, 1980.223. Blomquist, A. T.; Prager, J.; Wolinsky, J. J. Am. Chem. Soc. 1955, 77, 1804.224. Murov, S. L. Handbook of photochemistry; Marcel Dekker: New York, 1973.225. Bowen, J. P.; Pathiaseril, A.; Profeta, S. Jr.; Allinger, N. L. J. Org . Chem.1987, 52, 5162.226. Chang, G.; Guida, W. C.; Still, C. J. Am. Chem. Soc . 1989, 111, 4379.227. Turro, N. J.; Zhang, Z. In Photochemistry in solid surface, Ampo, M.;Matsura, T. Eds., Elsevier: Amsterdam; 1989, p. 197.228. Turro, N. J.; Zhang, Z. Tetrahedron Lett. 1987, 28, 5517.229. Wagner, P. J.; Hammond, G. S. J. Am. Chem. Soc. 1966, 88, 1245.230. Halpern, A.; Ware, W. R. J. Chem. Phys. 1970, 53 , 1969.231. Chandler, W. D.; Goodman, L. J. Mol. Spectr. 1970, 35, 232.

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.831.1-0061803/manifest

Comment

Related Items