UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Polypyrrolic macrocycles Sawka, Richard A. 1976

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

Item Metadata

Download

Media
831-UBC_1976_A6_7 S29.pdf [ 4.84MB ]
Metadata
JSON: 831-1.0061055.json
JSON-LD: 831-1.0061055-ld.json
RDF/XML (Pretty): 831-1.0061055-rdf.xml
RDF/JSON: 831-1.0061055-rdf.json
Turtle: 831-1.0061055-turtle.txt
N-Triples: 831-1.0061055-rdf-ntriples.txt
Original Record: 831-1.0061055-source.json
Full Text
831-1.0061055-fulltext.txt
Citation
831-1.0061055.ris

Full Text

POLYPYRROLIC MACROCYCLES by RICHARD A. SAWKA B.Sc. (HONS.), University of Alberta, 1973 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE . i n the Department of Chemistry We accept t h i s thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA September, 197 6 (5) Richard A. Sawka In presenting th i s thes is in pa r t i a l fu l f i lment of the requirements for an advanced degree at the Univers i ty of B r i t i s h Columbia, I agree that the L ibrary sha l l make it f ree ly ava i lab le for reference and study. I further agree that permission for extensive copying of th is thesis for scho lar ly purposes may be granted by the Head of my Department or by his representat ives . . It is understood that copying or pub l i ca t ion of th is thesis for f inanc ia l gain sha l l not be allowed without my written permission. Department of The Univers i ty of B r i t i s h Columbia 2075 Wesbrook P l a c e Vancouver, Canada V6T 1W5 i ABSTRACT Synthetic studies toward the preparation of several p o l y p y r r o l i c macrocycles are described. The majority of the research was di r e c t e d toward the synthesis of a pentapyrrolic analogue (15) of porphyrin (13). The r e s u l t s were sur p r i s i n g , as a meso-substituted porphyrin (63) was the r e s u l t . In l i g h t of our findings we were able to explain our e a r l i e r f a i l u r e s to obtain the pentapyrrole (15) as well as the f a i l u r e s of previous investigators^""*". A sapphyrin (16), the pentapyrrolic analogue of co r r o l e (2), was also prepared, for eventual comparison with our porphyrin analogue (15), and we attempted to i n s e r t into 2+ 29 xt a uranyl catxon (UC^ ). The uranyl moiety had been shown to be present i n a pentapyrrolic analogue (17) of phthalocyanine (68). By a reaction analogous to that for (17), the syn-th e s i s of the five-membered analogue (18) of benzporphyrin (see Scheme 13) was attempted. That macrocycle (18), containing the uranyl ion and being .more porphyrin-like than (17) , would have provided a l i n k between the *superphthalocyanine' (17) and the other macrocycles, (15) and (16). i i TABLE OF CONTENTS PAGE ABSTRACT i TABLE OF CONTENTS i i LIST OF SCHEMES AND FIGURES i i i ACKNOWLEDGEMENT i v ABBREVIATIONS V 1. INTRODUCTION 1 2. SYNTHESIS OF MACROCYCLE PRECURSORS 19 2.1 Tripyrromethanes 21 2.2 Dipyrromethanes 27 2.3 Bipyrroles 31 3. SYNTHESIS OF MACROCYCLES 30 3.1 Porphyrin Analogue 36 .. 3.2 Sapphyrin 64 3.3 Superphthalocyanine 70 3.4 Superbenzporphyrin 72 4. EXPERIMENTAL 75 5. REFERENCES 105 6. SPECTRA l l O i i i LIST OF SCHEMES SCHEME PAGE 1 P y r r y l c a r b i n y l cation formation 5 2 Coupling reactions producing decamethylsapphyrin (11).... 8 3 MacDonald Coupling 20 4 Knorr and Related Pyrrole Syntheses 22 5 Coupling producing Tripyrromethanes 24 6 Preparation of Tripyrromethanes 26 7 Preparation of Pyrrole necessary for Dipyrromethanes .... 28 8 Preparation of Dipyrromethanes 30 9 Preparation of Bipyrroles 32 10 Coupling reactions to porphyrin analogue (15) 38 11 Mechanism f o r preparation of meso-pyrrolyl porphyrin (63) 5 4 12 Clezy's meso-pyrrolyl porphyrin (67) synthesis 61 13 Mechanistic routes for the preparation of (15),(59)and(63) 62 14 Sapphyrin (16) synthetic route 64 15 Attempted preparations of Superbenzporphyrin (18) 73 16 Method of preparation of phthalocyanine (71) 74 LIST OF FIGURES FIGURE 1 Aetio and Rhodo spectra 43 i v ACKNOWLEDGEMENTS In any long term project the c r e d i t for any successes cannot go to one person alone, and t h i s i n v e s t i g a t i o n was no exception. F i r s t I must express my sincere gratitude for the confidence, encouragement and stimulation provided by David Dolphin over the past two years. I am thankful too for the comraderie and assistance of the Dolphin research group. Notably, that of Andrew Hamilton, with whom I had many enlightening "chats", Carl Alleyne, whose knowledge of things general and facts obscure always astounded me, Gene Johnson whose generosity with his experience never l e f t me wanting, Bob DiNello, Bob Carlson and es p e c i a l l y John B. Paine III whose help i s g r a t e f u l l y acknowledged. I would also l i k e to thank Joe Nip, a long-suffering mass spectroscopy technician who was' bombarded with many i n v o l a t i l e samples yet always managed to get the r e s u l t s . I am also g r a t e f u l for the help of Monica Reimer (who drew the diagrams) and Luanna Larusson whose fingers f a i r l y flew over the keys as she typed the th e s i s . F i n a l l y , I would most l i k e to thank my wife, Susan, without whose patience, understanding, generosity and love t h i s project (and i n p a r t i c u l a r t h i s thesis) would have been a great deal more d i f f i c u l t . V ABBREVIATIONS Terms of nomenclature used interchangeably i n the text include: Dipyrrane = Dipyrromethane (= 2,2 1-dipyrrolylmethane) Tripyrrane = Tripyrromethane (= 2,5-bis-(2-pyrrolylmethyl)-pyrrole) Pyrrole esters are re f e r r e d to as " 2-carbethoxy-3,4 ,.5-trimethyl-pyrrole" rather than "ethyl-3,4,5-trimethylpyrrole-2-carboxylate", the l a t t e r often found i n the l i t e r a t u r e . Abbreviations which may appear are (in random order): DMF = N,N-dimethylformamide THF = tetrahydrofuran TFA = t r i f l u o r o a c e t i c acid OEP = octaethylporphyrin OMP = octamethylporphyrin MP = melting point uncorr. = uncorrected L i t . = l i t e r a t u r e Hz. - Hertz (cycles per second) cone. = concentrated g.;ml.;i.r.;uv;nmr;cm ; etc. have the usual meanings. 1 1 . INTRODUCTION In 1960 Johnson and Price reported"*" the synthesis of some metal derivatives (1, M = Pd, Cu, Co) of corrole (2), the tetradehydro d e r i v a t i v e of the c o r r i n nucleus (3) of Vitamin This conclusion was subsequently scrutinized by 2 Woodward and Bauer . The claim that the product obtained from (I) (2) (3) the reaction of formaldehyde and aqueous ethanolic hydrogen chloride with a palladium chelate of a dibromo-bidipyrro-methenyl (4, M=Pd), was i n fact the corrole (1, M=Pd) seemed doubtful f o r , among other things, the alleged structure con-tained only 16 c y c l i c a l l y conjugated n-electrons (a 4n Hiickel number and therefore non-aromatic) . Woodward and 2 Bauer concluded that the product was the c y c l i c ether (5) which would have arisen from a nu c l e o p h i l i c attack by water on the e l e c t r o n - d e f i c i e n t dipyrromethene system rather than the e l e c t r o p h i l i c attack necessary to introduce a carbon 2 t h e i r e a r l i e r r e s u l t s Johnson and Kay concurred with t h i s i n t e r p r e t a t i o n . Woodward and Bauer then attempted to prepare an authentic corrole by treatment of the bi-dipyrromethane (6) (otainable by demetallation and hydrogenation of (4)) with formic acid. The r e s u l t was a m e t a l l i c blue glass which was dark green i n solution and was assumed to be the desired 4 corrole . In 1965 Johnson and Kay published a new report stating that a corrole (7) had been obtained by the photo-chemical c y c l i z a t i o n and oxidation of a biladiene (8). 5 Subsequently, the Woodward-Hoffmann Rules explained t h i s e l e c t r o c y c l i c reaction as proceeding i n the geometrically favored (conrotatory) a n t a r a f a c i a l manner only i n the photo-chemically accessible f i r s t excited state of t h i s 18 ir-electron Et Et- Et Et Et Et (6) (7) (8) system. The absorption spectra reported by Johnson f ( A m a x ( £ ) ) for the free base: 396 nm (123,100), 536 (18.100), 550 (18,100) and 593 (21,450); for the hydrobromide: 406 nm (138,000) and 477 (24,420)] were wi l d l y d i f f e r e n t from that which Woodward and Bauer observed for t h e i r product [4 58 nm (294,000), 613 (6,700), 643 (9,900), 670 (10,800) and 713 (5,400)] and t h i s new evidence warranted re i n v e s t i g a t i o n of the blue glass. Woodward and Bauer obtained a quantity of the perchlorate s a l t of t h e i r compound s u f f i c i e n t for analysis and the r e s u l t s were completely discordant with the proposed structure of t h e i r corrole (7). Most noticeable was the r a t i o of chlorine to nitrogen, found to be two to f i v e (whereas a corrole should form a monoperchlorate with a Cl/N r a t i o of one to four), suggesting a diperchlorate s a l t of a compound containing f i v e pyrrole rings, not four. Accordingly, the 4 structure of t h i s compound was concluded to be (9), and because of the c r y s t a l l i n e form and b r i l l i a n t blue color (reminiscent o f sapphires), was c a l l e d sapphyrin. Me Et I t seemed that, under the a c i d i c conditions of the synthesis, the bi-dipyrromethane (6), bearing no s t a b i l i z i n g e lectron-withdrawing substituents, had disproportionated into p y r r y l c a r b i n y l cations (see Scheme 1) . These, i n turn had reassembled into the macrocycle of maximum geometric s t a b i l i t y which was then oxidized to the observed product. Although the structure o f the sapphyrin i s o l a t e d was given as (10) , the same dispro-portionation reactions which led to i t s formation could have also caused randomization of the ori e n t a t i o n of.the other two no n - b i p y r r o l i c n u c l e i r e s u l t i n g i n a mixture of four possible isomers, which could be expected to be d i f f i c u l t to separate. The sapphyrin, which was the f i r s t known poly-p y r r o l i c macrocycle having more than four pyrrole rings, had a very intense, S o r e t - l i k e absorption band (458 nm) and r i n g -current-induced nmr s h i f t s (downfield from TMS for the external methine protons and u p f i e l d for the i n t e r n a l NH protons). 5 SCHEME il 6 Me Et Me Et Me Et Et Et (10) These c h a r a c t e r i s t i c s , p l u s the f a c t t h a t the sapphyrin system can be f o r m a l l y w r i t t e n as c o n t a i n i n g 22 c y c l i c a l l y conjugated i T-electrons (4n + 2, n = 5) , i n d i c a t e d t h a t the system was aromatic. by a rational, systematic route in order to: (a) provide chemical proof of the proposed structure, (b) obtain a com-., pound of known isomeric purity, (c) to give a compound whose nmr would reflect the symmetry of the system without undue complication and, (d) to obtain a derivative suitable for x-ray crystallographic analysis. The project was undertaken, with It was decided to synthesize decamethylsapphyrin (11) Me Me Me Me (M) 7 varying degress o f success, by a succession of researchers and 6 resulted i n a reaction sequence, pioneered by F.L. Harris 7 and optimized by Edith Wang , whereby s u f f i c i e n t decamethyl-sapphyrin was prepared. The f i n a l coupling components (shown i n Scheme 2) a l l resulted i n sapphyrin, i n d i c a t i n g that both major approaches succeeded: the coupling of a t e t r a -pyrrole with a monopyrrole (a "4+1" reaction) and the reaction o f a t r i p y r r o l e with a d i p y r r o l e (a "3+2" r e a c t i o n ) . The decamethylsapphyrin, obtainable from the reaction mixture i n 40% y i e l d , was n i c e l y c r y s t a l l i n e but extremely insoluble (octamethylporphyrin i s also very insoluble but i t s s o l u b i l i t y increases greatly when ethyl groups replace the methyls). The strong b a s i c i t y of the free-base sapphyrin (which abstracted hydrogen chloride from chloroform) made analysis d i f f i c u l t but prolonged heating i n vacuo resulted i n a s a t i s f a c t o r y combustion analysis. The nmr spectrum of the d i - t r i f l u o r o -acetate s a l t i n deuteriochloroform showed the expected deshielding o f the meso-protons (signals corresponding to 2H each at (6(ppm)) 11.71 and 11.80) and shielding of the NH protons (6(ppm): -4.884 (2H), -5.0 (1H), -5.46 (2H)). The absorption 7 spectrum of the dihydrochloride s a l t i n chloroform was found t o be: (A m (e)) 431.5 (56,000), 456.5 (594,000), 579 (3,400), 625 (14,000), 677 (20,000) and 689 (17,200) (Spectrum #1). p Concurrently, Broadhurst, Grigg and Johnson had prepared an analogue of sapphyrin, subsequently named dioxasapphyrin, with a bifuran moiety replacing the b i p y r r o l e . SCHEME 2 9 These authors also synthesized^ several other systems, a l l of which were aromatic: a sapphyrin, a dioxasapphyrin, a thiasapphyrin (with a thiophene replacing a p y r r o l i c unit) and two dioxanorsapphyrins ( i . e . , dioxasmaragadyrins - com-pounds containing the bifuran and having, i n addition, one other d i r e c t l i n k between pyrroles. King"*"^ also investigated macrocycles having two d i r e c t l i n k s and eventually produced compounds with non-adjacent d i r e c t l i n k s which he c a l l e d "smaragadyrin" a f t e r "sapphyrin" -a green compound which proved to be l i g h t s e n s i t i v e and less 9 stable than sapphyrin. (Johnson et a l had found t h e i r nor-sapphyrin too unstable to be isolated.) In view of these r e s u l t s , the synthesis of a penta-p y r r o l i c macrocyclic analogue of porphyrin (as sapphyrin i s the pentapyrrolicanalogue of c o r r o l e ) , i . e . a compound having no d i r e c t l i n k s , was considered. I t was determined"*""*" that there should e x i s t only one aromatic p o s s i b i l i t y , that containing 22 ir-electrons (12 a,b) . In the neutral macrocycle only two NH 10 protons could be accommodated, as i n porphyrin (there are three i n corrole and sapphyrin) and these could either be adjacent or non-adjacent r e s u l t i n g i n d i f f e r e n t arrangements of the three exocyclic double bonds (12 a,b, arrows) (double bonds not i n the conjugated system which, when reduced, should 0 not disturb the aromaticity of that system). The number of c y c l i c a l l y conjugated iT-electrons could be varied by changing the number of protonated pyrrole nitrogens. To go from one Huckel (4n + 2) system to another ( i . e . change n by one) requires a change of four NH protons. Among the macro-cyclopentapyrroles, the number of NH protons must be 0,1,4 or 5 to allow such a change and, since the proposed macrocycle . (12 a,b) would have two NH protons, the 22-TT system i s the only aromatic p o s s i b i l i t y . The aforementioned macrocycles (sapphyrin and the proposed pentapyrrolic porphyrin analogue) are novel compounds from not only a s t r u c t u r a l point of view. Close scrutiny of these systems reveals perhaps the most ex c i t i n g feature of these new classes of compounds - there are located, .in the planar r i n g , 22 i r - e l e c t r o n s arrayed i n c y c l i c , conjugated fashion. This number of ir-electrons corresponds to Huckel 1 s 12 Rule which predicts that planar, monocyclic, conjugated systems of t r i g o n a l l y hybridized atoms having a closed s h e l l configuration of (4n + 2) Tr-electrons w i l l possess r e l a t i v e e l e c t r o n i c s t a b i l i t y , i . e . w i l l be aromatic. By comparison 11 porphyrin systems (as i n (13)) contain 18 (another Huckel (4n + 2) number) ir-electrons i n a monocyclic conjugated planar system and t h e i r aromaticity has been confirmed as predicted by Huckel theory. Aromaticity may be defined i n a number of d i f f e r e n t ways and several d i f f e r e n t methods have been proposed for measurement of aromatic character. C l a s s i c a l l y , aromaticity was c o r r e l l a t e d with the presence of an 'aromatic sextet', the s t a b i l i t y of the compound, and i t s chemical r e a c t i v i t y . C l e a r l y , chemical r e a c t i v i t y i s not a ground state property of the compound but one dependant on the energy difference be-12 tween the ground and t r a n s i t i o n states. Huckel " has pointed out that aromaticity i s a function of the e l e c t r o n i c nature of the system, and not a property of s t a b i l i t y or chemical reac-. . 13 t i v i t y . Badger has also suggested systems defined i n terms of t h e i r e l e c t r o n i c structure: "An unsaturated c y c l i c or p o l y c y c l i c molecule or ion (or part of a molecule or ion) may be c l a s s i f i e d as aromatic i f a l l the annular atoms p a r t i c i p a t e i n a conjugated system such that, i n the ground state, a l l the 12 i r - e l e c t r o n s (which are derived from atomic o r b i t a l s having a x i a l o r i e n t a t i o n to the ring) are accommodated i n bonding molecular o r b i t a l s i n a closed (annular) s h e l l " . Consequently that system should contain "a measurable degree of c y c l i c d e l o c a l i z a t i o n of the Tr-electron system i n the ground state of the molecule" 1 4. A number of physical methods are currently used to measure the extent of i r - e l e c t r o n d e l o c a l i z a t i o n , and hence aromatic character. These include nmr spectroscopy, absorp-t i o n spectroscopy and x-ray crystallography. These and other techniques have been tested on the 18 i r - e l e c t r o n porphyrin system which i s predicted to be aromatic. One of the major differences between aromatic systems and conjugated c y c l i c or non-cyclic polyenes i s the fact that, in the non-aromatic systems, the carbon-carbon bond lengths are a l t e r n a t e l y long and short i n accordance with the alternate single and double bonds, whereas i n the aromatic compounds a l l the bonds are the same length - i . e . of the same double bond character. This double bond character i s unique (r e s u l t -ing i n bond lengths intermediate between those for single and double bonds) and not simply a r e l a t i o n s h i p between single and double bonds. In order to obtain t h i s double bond character, there must be maximum overlap between the a x i a l l y oriented p - o r b i t a l s and t h i s requires that the ri n g be planar. X-ray 15 cry s t a l l o g r a p h i c studies on porphine (13) and other porphyrin 13 systems have shown t h i s to be the case. E l e c t r o n i c absorp-t i o n spectra of aromatic compounds are also c h a r a c t e r i s t i c . ^Electronic t r a n s i t i o n s from lower to higher energy states cause absorption of v i s i b l e and u l t r a v i o l e t l i g h t . The energy difference between the state and the p r o b a b i l i t y of the t r a n s i t i o n occurring cause the s p e c i f i c absorption frequency and i n t e n s i t y , r e s p e c t i v e l y . Simple o l e f i n s , i n which the t r a n s i t i o n i s one of high energy, corresponding to a jump from a f i l l e d i r - o r b i t a l to an empty antibonding i r - o r b i t a l i n the ground state, thus have absorptions i n the u l t r a v i o l e t . Conjugated c y c l i c and polyenes with lower energy t r a n s i t i o n s absorb at longer wavelengths. However, the aromatic systems have degenerate h i g h e s t - f i l l e d molecular o r b i t a l s allowing a number of d i f f e r e n t t r a n s i t i o n s , the positions of which are determined by the resonance properties of the system. In porphyrins (where the large i r-electron d e l o c a l i z a t i o n produces strong resonance) a four-banded spectrum i n the v i s i b l e (450-700 nm) and a single, stronger (usually twenty times the strongest v i s i b l e band) absorption i n the near u l t r a v i o l e t (MOO nm) c a l l e d the Soret, are observed. The spectra have 17 18 19 been subjected to t h e o r e t i c a l treatment ' ' and the ca l c u l a t i o n s indicate that the v i s i b l e bands and the Soret 20 a r i s e from two separate t r a n s i t i o n s . The Soret i s calculated to be the band a r i s i n g from the energy difference (due to i T-electron d e l o c a l i z a t i o n ) between the highest occupied 14 molecular o r b i t a l and the lowest unoccupied molecular o r b i t a l . This allowed t r a n s i t i o n , which should appear i n the near u l t r a v i o l e t or v i s i b l e region, i s c h a r a c t e r i s t i c of an aromatic system. One other manner i n which the -rr-electron d e l o c a l i -zation manifests i t s e l f i s i n the sustaining of ring currents when placed i n an external magnetic f i e l d . Thus aromatic compounds i n the nmr should exhibit chemical s h i f t s of protons such that those inside the r i n g are strongly shielded (due to the r i n g current's opposition to the applied f i e l d ) and appear s h i f t e d u p f i e l d from TMS and protons outside the ri n g are strongly deshielded (the r i n g current strengthening the external f i e l d ) and appear downfield from TMS. Studies 21 on porphyrins by nmr spectroscopy c l e a r l y indicate the 22 presence of a r i n g current and the parent porphine (13) i n solution, i n t r i f l u o r o a c e t i c acid, exhibits resonances at (6(ppm)) 11.22 assigned to the four meso (or bridging-carbon) protons, at 9.92 the eight 6-protons (those at the periphery of the pyrrole r i n g s ) , and -4.4 for the protons on the r i n g nitrogens. Thus the presence of a strong ri n g current i s also an i n d i c a t i o n of aromaticity. One very important r e s u l t of the subsequent research to v e r i f y Huckel 1s Rule was the proposal that there exists an upper l i m i t for n i n the ,(4n + 2) rul e ; i . e . at c e r t a i n large ring sizes the systems stop being aromatic. Longuet-Higgins 15 and S a l e m ^ ' " , using simple L.C.A.O. theory, concluded that i n systems where n < 8 a l l the carbon-carbon bond lengths would be equal but i n systems with n > 8, the r i n g would be a system of a l t e r n a t i n g double and single bonds. The same c r i t i c a l value for n (which was given as an upper l i m i t only) was also found by Coulson and Dixon " using a valence-bond 2 6 resonance theory. Dewar and Gleicher , using a more refined approach, c o r r e l l a t e d calculated resonance energies for annulenes (monocyclic conjugated polyenes) with r i n g s i z e . They found the [4n]-annulenes (predicted to be non-aromatic) to have negative resonance energies and the [4n+2]-annulenes to have p o s i t i v e resonance energies and were, as predicted, aromatic. The resonance energy of the aromatic systems, how-ever, was found to decrease with increasing r i n g s i z e r e s u l t i n g i n a change from aromaticity to non-aromaticity in the Huckel 27 (4n + 2) systems between [22]- and [26]-annulene. Sondheimer , who has prepared an entire series of annulenes and dehydro-annulenes (annulenes having acetylenic linkages) of both the (4n) and (4n + 2) types, has found the (4n + 2) systems up to and including [18]-annulene (14) to be aromatic but systems equal to or greater than [26]-annulene to have no aromatic character. The (4n + 2) annulenes and dehydro-annulenes where n > 6 produce no r i n g current and exh i b i t no aromaticity but the systems where n < 4 do sustain a r i n g current and are aromatic. U n t i l the discovery of the sapphyrin system, (14) compounds r e l a t i n g to [22]-annulene (4n + 2, n = 5), though to be the l i m i t i n g r i n g s i z e for aromatic (4n + 2) i r -electron systems, were unknown. Sapphyrins (22 i r-electrons systems) and porphyrins (18 i r-electron systems) can be considered a special class of annulenes - namely those with bridging heteroatoms. Even though the nitrogen atoms must impart s p e c i a l c h a r a c t e r i s t i c s to these compounds they are c e r t a i n l y related to the simpler carbocyclic systems. The porphyrins have been shown to have aromatic properties possibly even stronger than t h e i r [18]-annulene counterparts. Sapphyrin has also demonstrated aromaticity and i t was, therefore, of i n t e r e s t to investigate other, related, 2 2 i r-electron systems with the hope of eventually comparing t h e i r aromatic character (or lack of i t ) with sapphyrin. E a r l i e r investigations 1"*", from which our studies were an offshoot, l a i d the synthetic groundwork so necessary i n a project of t h i s type. Their objective was, i n i t i a l l y , to prepare a decamethyl pentapyrrolic macrocycle (12 a,b) containing no d i r e c t l i n k s ( i . e . homologous to porphyrin) 6 7 analogous to the previously prepared decamethylsapphyrin ' . 17 At an early stage the decamethyl-compound precursors proved too insoluble for e f f i c i e n t study. In addition, one of the necessary coupling components (for the decamethyl-"super-porphyrin") could, under the reaction conditions employed, suffer coupling at a bridging p o s i t i o n (between two pyrroles) , rather than at a terminal pyrrole (see Chapter 2) r e s u l t i n g i n the eventual excision of the terminal pyrrole and the pro-duction of octamethylporphyrin. Thus components bearing e l e c t r o n -withdrawing groups were substituted to deactivate the methene bridges and the coupling reactions were attempted again, with encouraging r e s u l t s . At t h i s point our investigations began. We undertook to carry on the synthesis of the porphyrin homologue (15), as well as other p o t e n t i a l l y i n t e r e s t i n g systems. These included another sapphyrin (16) a metallated phthalocyanine (17, M = U0 2) (as o r i g i n a l l y prepared by 2 8 Bloor, Schlabitz, Walden and Demerdache and Day, Marks 29 and Wachter ) and, by an analogous reaction, a metallated pentaisoindolic homologue of benzporphyrin (18, M = U0 0). 18 f'7> (18) 19 2. SYNTHESIS OF MACROCYCLE PRECURSORS At the outset i t must be made clea r that perhaps the greatest d i f f i c u l t y inherent i n long synthetic schemes such as the one described here i s the large numbers of reactions, often with low y i e l d s , which must, be completed before the com-ponents are a v a i l a b l e for the f i n a l steps. Even with mediocre to good y i e l d s i n most of the reactions, one finds i t necessary to s t a r t on a kilogram scale with the f i r s t step i n order to have milligram quantities for the l a s t . The c l a s s i c a l example of t h i s i s demonstrated i n Woodward's chlorophyll synthesis where several garbage cans of pyrrole generated a comparable number of milligrams of c h l o r o p h y l l . Fortunately, the bulk o f the i n i t i a l synthetic work was previously performed on a grand s c a l e 1 1 and I was the fortunate r e c i p i e n t of those bountiful stocks. With them, r e p e t i t i o n of only the l a s t f i v e syntheses (in each series) was necessary i n order to b u i l d up supplies of the coupling components needed for t h i s study. As the main focus of our research was the penta-p y r r o l i c homologue of porphyrin (15), the coupling components were designed with that f i n a l compound in mind. We concluded 30 that a '3+2' reaction (Scheme 2) u t i l i z i n g the MacDonald coupling would be the most reasonable and e f f i c i e n t method of production of the macrocycle. (The MacDonald coupling, Scheme 3, u t i l i z e d i n the production of symmetrical porphyrins, 20 H H involves the acid-catalysed condensation of a 2 , 2'-diformyl-dipyrromethane (Scheme 3,A) with a 2 , 2'-diacid (or d i -unsubstituted) dipyrromethane (Scheme 3,B) r e s u l t i n g i n a por-phodimethene (Scheme 3,C) which i s oxidized in s i t u to the porphyrin (Scheme 3,D)). As mentioned previously, i t was also found^ ""*" that the i n s o l u b i l i t y and r e a c t i v i t y of the methyl-substituted compounds hampered further i n v e s t i g a t i o n of t h e i r properties. Hence the ethyl-ester substitutent was introduced on the central pyrrole of the tripyrfomethane as both a side chain r e a d i l y i d e n t i f i a b l e by nmr and mass spectroscopy and as an electron withdrawing group, which should t h e o r e t i c a l l y deactivate at least one of the bridging methylene positions with respect to e l e c t r o p h i l i c attack (the ester moiety would a t t r a c t electron density toward i t s e l f r e s u l t i n g i n a stronger C-H bond at the adjacent bridging methylene). S i m i l a r l y , f o r increased s o l u b i l i t y and ease of i d e n t i f i c a t i o n i n the mass spectrum and nmr, 3 , 4 - d i e t h y l p y r r o l e s were used i n the prepara-t i o n of the dipyrromethanes (Scheme 8) . Another aspect of pyrrole chemistry which found much use and great success was 21 the use of electron withdrawing esters (in the 2- or ex-position) as s t a b i l i z i n g groups for the p y r r o l i c nucleus and, more importantly, as precursors to carboxylic acid and aldehyde f u n c t i o n a l i t i e s . The stable, yet e a s i l y removable, benzyl esters eliminated the need for aldehyde protecting groups, such as the dicyanovinyl group, which generally re-quire the rather harsh conditions of prolonged action of 31 caustic a l k a l i to regenerate the aldehyde Thus the f i r s t objective was the synthesis of the building blocks. The enti r e synthesis of the coupling com-ponents described i n the next three sections i s included to i l l u s t r a t e the number and complexity of reactions i n addition to the manner i n which the compounds were made. More d e t a i l i s devoted to the more recent reactions. 2.1 Tripyrromethanes As indicated i n the previous section, the design of the tripyrromethane was such that an electron-withdrawing group was to be present on the ce n t r a l pyrrole i n order to deactivate one of the bridge p o s i t i o n s . Fortunately the Knorr synthesis 32 and related reactions (Scheme 4) yielded pyrroles of p r e c i s e l y the type needed. Knorr*s pyrrole (2,4-dicarbethoxy-3,5-dimethylpyrrole) (21) resulted from the condensation of ethyl acetoacetate (19) with i t s oximino counterpart (20) i n two steps. In a s i m i l a r manner, the very useful 2-carbethoxy-22 SCHEME 4 23 3,4,5-trimethylpyrrole (23) was obtained from ethyl acetoacetate (19) and 3-methyl-2,4-pentanedione (22). Preparation of the central pyrrole for coupling with the terminal pyrroles was c a r r i e d out following the sequence i n Scheme 5. Knorr's pyrrole (21) was oxidized with bromine 33 and s u l f u r y l chloride v i a Corwin's procedure (keeping the reaction mixture cold to avoid aldehyde formation) to the carboxylic acid (24). The acid (24) was monosaponified to the disodium s a l t of (25) on treatment with sodium hydroxide and was iodinated to (26) d i r e c t l y v i a sodium iodide i n sodium b i -carbonate. The reduction to the di-a-free pyrrole (2 7) 34 d i f f e r e d s l i g h t l y from Corwin's method i n that a stronger reducing agent and acid were required than the suggested com-bination of iodine, b i s u l f i t e and ac e t i c acid. A mixture of stannous chloride dihydrate, sodium iodide, hydrochloric acid and ethanol was found to e f f e c t the deiodination quickly and at r e l a t i v e l y low temperatures. A l l that remained was to couple the 3-carbethoxy-4-methylpyrrole (27) with two equiva-lents of the chloromethyl pyrrole (29) (Scheme 5) . The 2-carbobenzyloxy-5-chloromethyl-3,4-dimethyl-pyrrole (2 9) was obtained from 2-carbethoxy-3,4,5-trimethyl-pyrrole (23) v i a i n i t i a l l y , a t r a n s e s t e r i f i c a t i o n i n re-fluxi n g benzyl alcohol, employing sodium benzyloxide as the c a t a l y s t , to produce (28) , and secondly, a reaction of (28) i n d i e t h y l ether-methylene chloride with one equivalent of 24 SCHEME 5 25 s u l f u r y l chloride i n carbon t e t r a c h l o r i d e to prepare (29). The f i n a l coupling of (27) with two equivalents of (29), i n methylene chloride and at room temperature, afforded the 2,5-bis(5-carbobenzyloxy-3,4-dimethyl-2-pyrrolymethyl)-3-carbethoxy-4-methylpyrrole (30) i n 40-4 5% y i e l d . Removal of the biproduct symmetrical dipyrromethane (5,5'-dicarbobenzyloxy-3,3',4,4'-tetramethyl-2,2'-dipyrromethane) was r e l a t i v e l y easy, due to i t s d i f f e r e n t i a l s o l u b i l i t y , allowing r e c r y s t a l l i z a t i o n of the pale pink-orange tripyrrane (30) from tetrahydrofuran-methanol. The tripyrrane d i c a r b o x y l i c acid (31)(Scheme 6) was obtained by cleavage of the benzyl esters by c a t a l y t i c hydro-genation. As the d i a c i d was unstable i t was stored i n t e t r a -hydrof uran solution at 0°C i n the dark. (Under these condi-tions the compound i s stable f o r at least one year.) Reduction of the d i a c i d (31) to the dialdehyde (34) was accomplished i n two steps. The f i r s t was decarboxylation to the di-a-free tripyrrane (32) i n r e f l u x i n g N,N-dimethylformamide under an i n e r t (nitrogen) atmosphere. The second step involved formyla-t i o n i n cold DMF, using a s l i g h t excess of benzoyl chloride, to give the di-iminium s a l t (33) (an i s o l a b l e product) which underwent a l k a l i n e hydrolysis to give the desired stable dialdehyde (34). 27 2.2 Dipyrromethanes The pyrrole (43) necessary for coupling to the dipyrromethane component was prepared according to the series 35 i n Scheme 7. Kenner 1s procedure, because of i t s economy of reagents,was chosen as the procedure best suited to the preparation of the f i r s t major compound - ethylpropionyl-acetate (38). The reaction of ethoxymagnesium diethylmalonate (36) (prepared from diethylmalonate (35)) with propionyl chloride followed by a b o i l i n g water hydrolysis resulted i n (38). However the i n d u s t r i a l grade reagents u s e d 1 1 were impure and (38) was found to be contaminated with diethylmalonate (35). Rather than lower the y i e l d i n an attempt to p u r i f y (38) , i t was used i n the impure form for the remaining reactions (resulting in impurities (40) and (42)). The impure e t h y l -propionylacetate (38) was nitrosated with aqueous sodium n i t r i t e i n acetic acid to (39) which, when treated with 2,4-pentanedione,resulted i n 4-acetyl-2-carbethoxy-3-ethyl-5-methyl-pyrrole (41). The product (41) was reduced by the procedure 3 6 of Whitlock and Hanauer , using excess diborane to reduce the carbonyl to methylene, leaving the ester untouched. The 37 impurity (42) (thought to have arisen from Kleinspehn's documented reaction of diethyloximinomalonate (4 0) with 2,4-pentanedione under Knorr conditions) was unaffected by the reduction and, possessing a g-free p o s i t i o n , was susceptible to e l e c t r o p h i l i c attack. Thus the Mannich reaction was employed, 28 SCHEME 7 (35> 0 0 Mg ETOH b o 0 0 Et,0 (36) V 0 0 (39)N SN0 2 HOAc -.0 0 (37) H20 reflux 4 ^ 0 o (40) b b (38) o o ( 3 5 ) (43) - '..iJw<•»> 29 (refluxing the mixture of (42) and (43) i n ethanol with an excess of formaldehyde and diethylamine with a c a t a l y t i c amount of hydrochloric acid) r e s u l t i n g i n the formation of 2-carbethoxy-4-N,N-diethylaminomethyl-3,5-dimethylpyrrole (44) which was extracted from the ethereal solution with aqueous hydrochloric acid. The desired product 2-carbethoxy-3,4-diethyl-5-methylpyrrole (4 3) was then obtained by c r y s t a l l i z a -t i o n from ether. Having synthesized the pyrrole (43), the next step was to prepare the symmetric dipyrromethane. This was done v i a the method of C l e z y ^ as depicted i n Scheme 8. The s t a r t i n g material, 2-carbethoxy-3,4-diethyl-5-methylpyrrole (43), was trans-e s t e r i f i e d i n the usual manner (refluxing benzyl alcohol with sodium benzyloxide c a t a l y s t followed by quenching i n a mixture of methanol, water and a trace of g l a c i a l a c e tic acid). The benzyloxy ester pyrrole (45) was then acetylated using one equivalent of lead tetraacetate. The 5-acetoxymethyl-2-carbobenzyloxy-3,4-diethylpyrrole (46) could be iso l a t e d by c r y s t a l l i z a t i o n from hexane or could be coupled, using 39 Johnson's procedure, by b o i l i n g i n methanol, with a l i t t l e hydrochloric acid, to form the dipyrromethane (47). If the acetoxymethylpyrrole (4 6) were is o l a t e d , the mother l i q u o r s , i n methanol, could be coupled d i r e c t l y , using the aforementioned procedure, to increase the f i n a l y i e l d of dipyrromethane. The 5,5'-dicarbobenzyloxy-3,3',4,4 1-tetraethyl-2,2'-dipyrromethane (47) was converted to the d i a c i d (48) by 31 c a t a l y t i c hydrogenation i n tetrahydrofuran. As with the tripyrroraethane d i a c i d (31), high r e a c t i v i t y of the d i -pyrrane d i a c i d (48) necessitated i t s storage as a THF solution i n the r e f r i g e r a t o r i n the dark. For conversion to the dialdehyde (51), the tetrahydrofuran was removed i n vacuo and the greenish-white d i a c i d residue was dissolved i n N,N-dimethylformamide and thermally decarboxylated by r e f l u x i n g the s o l u t i o n i n an i n e r t atmosphere producing the di-a-free compound (49). Formylation was accomplished by cooling the N,N-dimethylformamide solut i o n of (49) and adding an excess of benzoyl chloride. The resultant di-iminium s a l t (50), which c r y s t a l l i z e d overnight was, a f t e r i s o l a t i o n , r e a d i l y hydrolysed to the product, 5,5'-diformyl-3,3',4,4 1-tetraethyl-2,2'-dipyrromethane (51). The dipyrrane dialdehyde (51) was, as predicted, soluble i n most organic solvents (e.g. methylene chloride, ethanol, methanol) and was r e a d i l y r e c r y s t a l l i z e d from ethanol. 2.3 Bipyrroles The bipyrrole necessary for the sapphyrin syntheses was prepared v i a an Ullmann coupling following the procedure of 40 Grigg and Johnson . Here though, the key pyrrole, 2-carbethoxy-3,4,5-trimethylpyrrole (23) had already been prepared (see Scheme 4) and the synthetic route leading to the desired b i p y r r o l e i s shown i n Scheme 9. 32 SCHEME 9 33 The s t a r t i n g material (23) was oxidized i n methylene chloride and d i e t h y l ether using an excess of s u l f u r y l chloride. A methylene chloride s o l u t i o n of the s u l -f u r y l chloride was added to the s t a r t i n g material i n methylene chloride immediately a f t e r the addition of the ether to pre-vent p r e c i p i t a t i o n of (23) from the ethereal solution. After s t i r r i n g , evaporation of the solvent i n vacuo resulted i n a red-brown o i l which was hydrolysed i n aqueous acetone. Re-moval of the acetone by d i s t i l l a t i o n allowed the product, 2-carbethoxy-5-carboxy-3,4-dimethyl-pyrrole (52) to c r y s t a l l i z e . R e c r y s t a l l i z a t i o n was determined to be unnecessary as the product showed no s t a r t i n g material by t h i n layer chromatography, and the carboxylate was iodinated by d i s s o l u t i o n i n aqueous sodium bicarbonate followed by the addition of 1,2-dichloro-ethane and a slight' excess ( t o t a l of 1.2 equivalents) of iodine, and an equal weight of sodium iodide. Heating the mixture to r e f l u x completed the reaction. (The r e f l u x tempera-ture (71°) was that of the 1,2-dichloroethane-water azeotrope and almost the i d e a l temperature (70°) for the reaction. Thus both a good solvent mixture and a simple means of tem-perature regulation were obtained simultaneously.) Sodium b i s u l f i t e was added to the reaction mixture p r i o r to workup to destroy any r e s i d u a l iodine - but had to be added very slowly, a few c r y s t a l s at a time, because of the effervescence of the r e s u l t i n g reaction. 34 The coupling of the iodopyrrole (53) with i t s e l f was accomplished v i a the Ullmann reaction using copper bronze i n N,N-dimethylformamide at 100°C. For workup, a l l that was required was f i l t r a t i o n to remove the copper bronze, extraction of the N,N-dimethylformamide by acid and water, a i r drying, and p u r i f i c a t i o n of the product by t r i t u r a t i o n with petroleum ether. This procedure afforded a 20-25% y i e l d of l i g h t tan 2,2'-dicarbethoxy-3,3 1,4,4'-tetramethyl-5,5'-bipyrrole (54). To i l l u s t r a t e the v e r s a t i l i t y of the t r a n s e s t e r i f i -cation procedure i n benzyl alcohol with sodium benzyloxide, the reaction was ca r r i e d out, i n t h i s series, a f t e r cqupling to the b i p y r r o l e (54) whereas for the tripyrromethanes and dipyrromethanes, only uncoupled monopyrroles were t r a n s e s t e r i f i e d . An excellent y i e l d (82.1%) of the dicarbobenzyloxybipyrrole (55) was obtained i n t h i s manner. C a t a l y t i c hydrogenation by the usual method resulted i n the b i p y r r o l e dicarboxylic acid (56) . The decarboxylation of the b i p y r r o l e was f a c i l i t a t e d , not thermally i n r e f l u x i n g N,N-dimethylformamide under nitrogen as described previously, but under the milder con-d i t i o n s obtained by d i s s o l v i n g i t i n t r i f l u o r o a c e t i c acid. Removal of the t r i f l u o r o a c e t i c acid i n vacuo l e f t the 3,3',4,4'-tetramethyl-5,5'-bipyrrole (57). Formylation of the d i - a -free pyrrole (57) required the use of the Vilsmeier-Haack 4 1 reagent - phosphorous oxychloride, i n cold N,N-dimethylforma-mide with slow, gentle warming and a l k a l i n e hydrolysis to 35 complete the reaction. That Vilsmeier reagent was chosen be-cause the acidity, of the phosphorous oxychloride was not c r i t i c a l as there were no a c i d - l a b i l e substituents. The f i n a l product, 2,2'-diformyl-3,3',4,4 1-tetramethyl-5,5'-bipyrrole (58), was pure as formed and could be used without recry-s t a l l i z a t i o n . Having prepared the precursors, the next objective • was the preparation of the macrocycles. 36 3, SYNTHESIS OF MACROCYCLES The synthesis of the macrocycles presented perhaps the greatest challenge of the e n t i r e project. There had been only one report of the preparation of the superphthalocyanine (18), a few more of sapphyrin (as (10) or (11)), and none at a l l of a porphyrin analogue (15) or a superbenzporphyrin (18). With those facts i n mind, we began our investigations. 3.1 Porphyrin Analogues As the synthetic routes followed i n the course of t h i s research c l o s e l y mimiced those employed i n the success-f u l synthesis of decamethylsapphyrin, i t was decided that the conditions for the f i n a l coupling.reaction s i m i l a r also. -3 The 3 + 2 condensation was effected at high d i l u t i o n (10 -4 to 10 molar) to minimize l i n e a r intermolecular polymeri-zation, and at room temperature to reduce random fragmen-t a t i o n . Comprising the bulk of the research, the coupling reaction i s best discussed i n three sections - the f i r s t covering the reaction and i t s conditions, the second t r e a t -ing the workup and analysis procedures and the t h i r d describing the conclusions drawn from our experiments. 37 3.1.1 Coupling Reaction The coupling was attempted, i n i t i a l l y , with the t r i -pyrromethane dialdehyde (34) and the dipyrromethane d i a c i d (48) although i n l a t e r reactions the tripyrrane d i a c i d (31) and dipyrrane dialdehyde (51) were used (see Scheme 10). The solvents employed for the reaction were, i n i t i a l l y , methanol, and l a t e r , methylene chloride. . Methanol had been the solvent of choice during the i n i t i a l i n v e s t i g a t i o n of t h i s system 1 1 and for the decamethyl sapphyrin synthesis. We switched from methanol to methylene chloride i n the early stages of the research since we discovered that we did not ob-serve the same spectral changes that o t h e r s 1 1 had noted i n methanol. The change of solvent also prompted a change of the acid c a t a l y s t . The p-toluene s u l f o n i c acid, which had been extremely useful i n methanol, would have had a decreased a c i d i t y i n the methylene chloride so we opted for saturation of r e d i s t i l l e d methylene chloride with anhydrous hydrogen chloride gas. The solution was sotred i n the r e f r i g e r a t o r and the small amounts necessary for reactions were dispensed from that stock solution. Because of the d i f f i c u l t y and indeed, the v a l i d i t y , of measuring pH i n non-aqueous media, the amounts of c a t a l y s t used were reported as m i l l i l i t r e s of HCl-saturated 42 methylene chloride . The reaction time was generally found to be inversely porportional to the amount of acid used. The technique of varying the amount of c a t a l y s t was 39 employed to observe the d i f f e r e n c e between a slow reaction and a rapid one. A f a s t reaction, u t i l i z i n g a large amount of acid was found to more rapidl y produce decomposition or side pro-ducts ( i . e . , any products which, on analysis, were porphyrins or were uncharacterizeable). However, a long-term reaction, using a small amount of c a t a l y s t , would also produce the same or s i m i l a r products,so c l e a r l y a compromise was necessary. The optimum conditions appeared to be a f i n a l a c i d concentra-t i o n of 3 x 10 4 M (one ml. of c a t a l y s t added) in^the reaction mixture (60-65 ml solvent) and t h i s allowed the reaction to be worked up i n 24 to 36 hours. By way of contrast, an acid - 4 concentration of 1.2 x 10 M (0.4 ml c a t a l y s t added) required the reaction mixture to s t i r for three or four days, whereas the addition of any less acid meant the reaction would take at least s i x days to complete. The reactions were monitored i n a v a r i e t y of ways, the p r i n c i p a l one being e l e c t r o n i c absorption. The v i s i b l e and n e a r - u l t r a v i o l e t regions of the spectrum were found most usef u l . Porphyrins and corroles have Soret bands in the neighbor-hood of 400 nm. and sapphyrins have a s i m i l a r absorbance around 450 nm; so i t seemed reasonable to assume that any pentapyrrolic macrocycle we prepared would absorb i n t h i s region also. A strong absorption at 456 nm. had been previously observed1"*" but i t unfortunately disappeared on workup of the reaction and was not observed i n any of the resultant 40 chromatographic f r a c t i o n s . We observed an i n i t i a l absorption at 505 nm. followed by the appearance of a shoulder at 450 nm. The i n t e n s i t y of the 450 nm. absorption increased more ra p i d l y than that at 505 nm. and eventually became a strong band (X 458 nm.) which surpassed, i n i n t e n s i t y , the 505 nm. v max r ' absorption (Spectrum #2). We discovered, while investigating the e f f e c t of extra acid c a t a l y s t on a sample of the reaction mixture, i n a 1 cm. spectrophotometer c e l l , that additional acid caused the 505 band to almost disappear and the i n t e n s i t y of the 458 hand to be increased enormously. Conversely, addition of a base such as triethylamine to the sample resulted i n a disappearance of the 458 band with con-comitant growth of the 505 band. We interpreted these re-s u l t s as the presence of two species i n solution - a protonated form (X 458 nm.) and a deprotonated form (X 505 nm.) of max max the suspected macrocycle (or porphyrinogen-like precursor to the macrocycle). Consequently during our workup procedure we were unperturbed at the loss of the 458 nm. absorption and assumed i t to be due to deprotonation of whatever species was i n solution (for the 505 nm. band remained during workup). The appearance of an absorption at 488 nm. (Spectrum #2) ( f i r s t as a shoulder on the 505 nm. band and eventually as the dominant absorption) was observed i n either old reaction mixtures or those containing a great deal of acid and indicated the demise of the reaction. Unless worked up quickly, no 41 characterizeable products were i s o l a t e d . The f i r s t appearance of a shoulder at 488 nm. was used as an ind i c a t o r for completion of the reaction. Attempts were made to monitor the disappearance of the reactants as well as the formation of any products. Thin-layer chromatography (tic) was t r i e d i n i t i a l l y but was found to be a slow and i n d e f i n i t e measure of the state of the mix-ture. T i c indicated a large number of species present i n the reaction mixture, and p o s i t i v e i d e n t i f i c a t i o n of the s t a r t i n g materials among them was d i f f i c u l t . A d d i t i o n a l l y , the fact that the reaction was run at high d i l u t i o n decreased the e f f e c -tiveness of t i c as a monitoring technique. The u.v. spectrum of the reaction mixture was ob-served f o r a time but multiple absorptions for both the tripyrrane dialdehyde (34) (A (nm.) 271, 314) and dipyrrane d i a c i d rrtcix (48) (X (nm.) 275 (sh), 290), and absorptions of some i n t e r -max mediate species complicated the spectrum to such a degree that r e l i a b l e i n t e r p r e t a t i o n was not possible. 43 High pressure l i q u i d chromatography (HPLC) was used to e f f e c t a separation of the reaction mixture into i t s com-ponents. This technique involved the use of a gel permeation column which separated components on the basis of s i z e , the largest compound being eluted f i r s t . Although t h i s method was attempted only once, i t was possible to monitor the d i s -appearance of the d i - and t r i - p y r r o l i c compounds and the 42 appearance of two larger compounds - one probably a t e t r a -pyrrole (most l i k e l y a porphyrin) and one larger s t i l l , as indicated by the more rapid e l u t i o n (perhaps a pentapyrrole). I t was noted from the HPLC r e s u l t s , that the dipyrrane disappeared at a r e l a t i v e l y f a s t e r rate than the tripyrrane which might indicate the presence of a competing process re-s u l t i n g i n the formation of a porphyrin. Because of t h i s ob-servation, subsequent reactions contained an excess of the d i -pyrromethane, on the assumption that the formation of a pentapyrrolic macrocycle would be a less-favored reaction than the formation of a porphyrin. The octaethylporphyrin, which should be the product of t h i s 2 + 2 coupling, had been observed 1 1. Overall, the most rapid, convenient and s e n s i t i v e method of monitoring the reactions was v i s i b l e and near-u.v. spectroscopy. The reaction mixtures were s t i r r e d , i n the dark, at room temperature and monitored u n t i l the f i r s t observation of an absorption at 4 88 nm, s i g n a l l i n g that the workup of the reaction need begin. The mixture of coupling components re-mained e s s e n t i a l l y c o l o r l e s s i n solution u n t i l the c a t a l y s t was added, causing the s o l u t i o n to become pale orange. The o color deepened with time but was not as precise a measure of completeness of reaction as v i s i b l e spectroscopy,as the decompo-s i t i o n products (A 488 nm.) were of s i m i l a r color. In the ^ max reaction to produce sapphyrin (11) the appearance of a dark green color indicated the completion of the reaction. 43 3.1.2 Workup Procedures Previous workers i n t h i s a r e a 1 1 were able t o i s o l a t e only porphyrins (although some i n t e r e s t i n g s p e c i e s , about which more w i l l be s a i d l a t e r , were observed). The workup procedure used i n t h a t work d i d not g e n e r a l l y i n v o l v e removal of the a c i d . On one occasion the a c i d was e x t r a c t e d w i t h aqueous sodium bicarbonate but there too only porphyrins were i s o l a t e d . From t h e i r mass s p e c t r a l analyses two types of porphyrins were found: o c t a - a l k y l porphyrins which gave an ' a e t i o ' spectrum (Figure 1) i n the v i s i b l e r e g i o n ( i . e . , m/e = 534 f o r o c t a -e t h y l p o r p h y r i n a r i s i n g from the condensation of the di p y r r a n e FIGURE I ~ T 1 " — l :—1 i •— 600 (nm) 600 600 (nm) dialdehyde (51) w i t h i t s e l f ) , or monoester porphyrins which 44 e x h i b i t a 'rhodo' spectrum due t o the e f f e c t of the e l e c t r o n -withdrawing e s t e r moiety ( i . e . , m/e 536 f o r a t e t r a e t h y l , t r i m e t h y l , monoester p o r p h y r i n (59) a r i s i n g from the c o u p l i n g r e a c t i o n s w i t h e x c i s i o n of the t e r m i n a l p y r r o l e of the t r i p y r r a n e (34) 44 Fearing that these observed products were due i n large part to the acid c a t a l y s t remaining during workup, our methylene chloride reaction mixtures were extracted with two volumes of d i s t i l l e d water p r i o r to chromatography. No base was used as we found the water was s u f f i c i e n t to ne u t r a l i z e , by extraction of the HC1, the organic phase. This washing resulted i n a color Change of the solution from orange-brown to brown. This also changed the spectrum, as mentioned e a r l i e r with the disappearance of the 458 nm. band, an increase i n the 505 nm. absorption and better d e f i n i t i o n of the absorbance of 488 nm. The appearance of an absorption at 405 nm. was also noted at t h i s time. This absorbance, though of lower r e l a t i v e i n t e n s i t y than those at 488 and 505 nm. was s t i l l intense. After chromatography, the 405 nm. band was found to be the Soret for a porphyrin which exhibited a 'rhodo' spectrum and was the f i r s t compound eluted from either preparative plates (Analtech, S i l i c a Gel GF) or columns (Woelm, S i l i c a Gel G) (m/e = 536, i . e . , the monoethyl ester porphyrin (59)). Following extraction of the acid, the reaction solution was dried (passage through Whatman Phase Separating Paper was found to be s u f f i c i e n t ) , then evaporated to dryness i n vacuo and the mixture redissolved i n a minimum amount of solvent and chromatographed. Column chromatography (2 x 3 0 cm i.d/column, 25 g. Woelm S i l i c a Gel G, A c t i v i t y II or IV) with methylene chloride/methanol (10:1) was the o r i g i n a l method of choice (the solvent system was determined by t i c studies) 45 but, because of the d i f f i c u l t y i n obtaining pure f r a c t i o n s , and the large amount of solvent required to elute slower-running species, the column method was superceded by s i l i c a gel preparative plates. Chromatography on these thick-layer plates (Analtech, S i l i c a Gel GF, with fluorescent i n d i c a t o r , 2000 y thickness, 20 x 20 cm. area ) with methylene c h l o r i d e / methanol (10:1) was found to give more reproducible separations, was much more economical i n terms of solvent used and permitted easier i d e n t i f i c a t i o n of the products (for example, porphyrins could be q u a l i t a t i v e l y detected by t h e i r fluorescence under u.v. (366 nm.) l i g h t ) and more f a c i l e i s o l a t i o n s (the band of the compound on the plate could be scraped o f f and the com-pound eluted from the s i l i c a gel with a more polar solvent system such as methylene chloride/methanol (1:1)). Another drawback to the use of column chromatography which was overcome by the use of plates was the need to examine (spectroscopically) a l l f r a c t i o n s , combine l i k e ones and concentrate them p r i o r to further analysis. Compounds having an r . f . lower than 0.4 on the plate were generally found to be uncharacterizeable by mass spectro-scopy ( i . e . , parent peaks of e i t h e r very low m/e i n d i c a t i n g fragments, or very high m/e i n d i c a t i n g polymer formation). The bands of r . f . >0.4 were also found to comprise the major products so the slower moving species were discarded. The chromatographed products, once removed from the s i l i c a g e l , 46 were examined by v i s i b l e absorption spectroscopy. To a l l the spectral samples were added, f i r s t acid ( t r i f l u o r o a c e t i c a c i d ) , and then base (triethylamine) to note the e f f e c t of acid and base on the species and to hopefully regenerate the i n t e r e s t i n g 458 nm. absorption. Unfortunately, the e f f e c t s of these acid additions were often not completely r e v e r s i b l e , i n d i c a t i n g an i r r e v e r s i b l e reaction of the species i n solution with the acid rather than the simple protonation/deprotonation mechanism o r i g i n a l l y envisaged. Samples with i n t e r e s t i n g spectra (spectra with absorptions i n either the 450 or 500 nm. regions, e s p e c i a l l y i n acid) were evaporated to dryness and submitted for mass spectral analysis. The mass spectral r e s u l t s were interpreted using the method developed by J.E. Paine I I I 1 1 for determining the em-p i r i c a l i d e n t i t y of any porphyrin (or any pentapyrrolic macro-cycle) formed. The s t a b i l i t y of porphyrins i n the mass spectro-45 meter i s well characterized and the base and parent peaks• are almost i n v a r i a b l y the same. With the systems we used, only the 3,4-diethyl-, 3,4-dimethyl-, or 3-carbethoxy-4-methyl pyrroles should be present i n any porphyrin produced. Since the lowest-mass porphyrin possible would be octamethylporphyrin (OMP, C28 H30 N4' m / / e 4 2^) > t n e difference between the parent mass observed and that for OMP should be due to any extra g-substituents present. Thus the presence of a di e t h y l p y r r o l e adds C»H. or 28 mass units and a 3-carbethoxy-4-methylpyrrole 47 moiety adds C 2 H 2 ° 2 o r ^ mass units to the m/e for OMP. A l l that i s required then i s an accurate mass count,for two d i e t h y l -pyrroles would add (2 x 28) 56 mass units, only two d i f f e r e n t from that due to the pyrrole ester. However, these two com-pounds should be e a s i l y .differentiated v i a u . v . - v i s i b l e spec-troscopy, since an ester substituent on a porphyrin changes the 44 absorption spectrum from an 'aetio' to a 'rhodo' type . This method might be extended to the pentapyrrolic systems where the simplest possible macrocycle can be assumed to be the decamethyl porphyrin homologue (C^gH^N , m/e 52 7) to which sub-* s t i t u t e n t s could be added (assuming, of course, that the macro-cycle has the same s t a b i l i t y i n the mass spectrometer as that of the porphryins have). Much to our disappointment the most common base peak observed i n the mass spectra of these products was m/e 536 which corresponded to a porphyrin containing two d i e t h y l -p y r r o l i c moieties, one dimethyl- and one 3-carbethoxy-4-methyl pyrrole (59). This compound would have arisen from attack at the bridge p o s i t i o n of the tri p y r r a n e (34) with the loss of the terminal dimethyl pyrrole. This product was to prove s i g n i f i c a n t i n the l i g h t of l a t e r r e s u l t s . On several occasions a parent peak at m/e 64 7 was observed which was six units higher than the mass of the proposed macrocycle. This phenomenon had been observed by others" using a s l i g h t l y d i f f e r e n t system and was interpreted as a macrocycle with a l l 48 49 of i t s three exocyclic double bonds completely reduced (60). This would add six hydrogens to the compound and consequently increase the parent mass by six u n i t s . Another p o s s i b i l i t y for a compound of m/e 647 i s the pentapyrrolic analogue .of a porpho-dimethene or 'raacrodimethene* (61). The observance of t h i s m/e 647 peak could not be c o r r e l a t e d with any s p e c i f i c mode of reaction, e i t h e r i n the manner the reaction was c a r r i e d out, the amount of acid added, or i n the workup. Whether the species was formed i n a l l cases i s not known, but i t did not appear consist n t l y i n the mass spectrum. Indeed, i n some cases where the 647 peak was observed as the parent, the m/e = 536 was seen to be the base peak, suggesting some decomposition, possibly v i a cleavage and rearrangement, of a pentapyrrole to a porphyrin. Whether the m/e 647 compound observed was the 'macro-dimethene'(61) of the macrocycle with the reduced exocyclic double bonds (60) i t was obvious that the oxidation had not (60) (61) 50 been completed i n the i n i t i a l reaction. It was also reasonable to assume that oxidation of ((60) or (61) should, i f our pre-d i c t i o n were correct, produce the desired macrocycle. Accordingly, iodine was added d i r e c t l y to the reaction mixture approximately one hour a f t e r the addition of the acid c a t a l y s t . This had been used successfully i n the synthesis of dioxa-46 sapphyrin (where the product was found not to form without the oxidative power of io d i n e ) . In our system, however, iodine proved too strong an oxidant and uncharacterizeable products resulted. 2,3-Dichlpro-5,6-dicyano-l,4-benzoquinone (DDQ) was then u t i l i z e d as an oxidant. Rather than e f f e c t the oxidation a f t e r mass spectral analysis, fearing that decomposition might occur i n the interim, we oxidized the crude reaction mixture (following a general procedure 4 7 for DDQ oxidations) immediately a f t e r extraction of the acid and p r i o r to chromatography. The water-washed and dried methylene chloride solution of products was evaporated to dryness i n vacuo, then dissolved i n a minimum amount ( 2 ml) of dry 1,4-dioxane and to t h i s was added, i n 1-3 ml of dioxane, the r e q u i s i t e amount of DDQ (assuming the molecular weight of the crude products to be 647 and that three equivalents of DDQ were required for each equivalent of product). The mixture was placed i n a 10 ml. round bottom f l a s k equipped with a r e f l u x condenser and magnetic s t i r r e r , and was refluxed one hour, cooled and f i l t e r e d to remove any reduced DDQ and other insoluble p r e c i p i t a t e s then evaporated to dryness i n vacuo. The s o l i d s were redissolved i n methylene 51 chloride and chromatographed on a preparative plate i n the usual manner. Examination of the developed plate under the u.v. l i g h t (366 nm.) was almost enough to dash our slim hopes, for i t indicated the major products to be porphyrins (strong red fluorescence i n two bands, both near the solvent front. None-theless we examined the compounds. The f i r s t product ( r . f . 0.9) exhibited a rhodo type v i s i b l e spectrum (X (nm.) 405 1 c ^ max (Soret), 508, 548, 572, 631) ( i . e . (59)) and t y p i c a l porphyrin behavior toward acid and base. Protonation of porphyrins, by acid generally causes only a s l i g h t s h i f t of the Soret to longer wavelength but great change i n the v i s i b l e region. One observes a collapse of the four-banded spectrum to one of two bands of s i m i l a r i n t e n s i t y . Addition of base simply deprotonates the porphyrin and regenerates the o r i g i n a l spectrum. The second compound eluted ( r . f . 0.7-0.8) also exhibited a por-phyrin spectrum, t h i s one of the 'aetio' type (^ m a x( n r n*) 410 (Soret), 510, 547, 575, 628) (Spectrum #3). The addition of t r i f l u o r o a c e t i c acid caused that solution to become green (again, a c h a r a c t e r i s t i c of protonated porphyrins) and the spectrum to change markedly. The Soret was s t i l l v i s i b l e at 410 nm. but there was also a strong absorption at 44 0 nm. (See Spectrum #3). In the v i s i b l e region the four band spectrum collapsed to two bands but, rather than the two centre bands increasing i n i n t e n s i t y (as i s common for porphyrins), the two absorptions at longest wavelength increased. The 52 absorption changes were t o t a l l y r e v e r s i b l e by the addition of base (triethylamine). Mass spe c t r a l analysis (Mass Spectrum #1) indicated a parent peak at m/e 657 (m/2e = 378.5 was also observed) and a base peak at m/e 535 (m/2e = 267.5 observed a l s o ) . This product, with an apparent mass of 657 (16 units higher than the proposed macrocycle) was confusing at the time and not u n t i l work was already underway on the sapphyrin and superphthalocyanine syntheses was i t s unusual spectrum recon-sidered. Although the" two band spectrum at long wavelength was e a s i l y r a t i o n a l i z e d as a protonated porphyrin, the large s h i f t of the Soret from 410 to 440 nm. and the abnormally high parent peak m/e were not so r e a d i l y explained. Woodward had 48 shown i n h i s synthesis of chlorophyll a_ that porphyrins with bulky substitutents at a meso p o s i t i o n and the two adjacent 8-positions were highly strained and would, on the addition of acid, be r e a d i l y protonated at the meso p o s i t i o n , changing the 2 hybridization of that carbon from sp (trigonal planar) to 3 sp (tetrahedral), thereby r e l i e v i n g the s t e r i c s t r a i n . That protonated compound, a p h l o r i n , was known to exhibit an absorption i n the region of 440 nm (the s h i f t of the Soret due to the break i n the conjugation) so characterization of our compound was attempted with t h i s i n mind. The mass spectral data were reinvestigated f i r s t . The parent peak at 657 was i n i t i a l l y considered anomalous because 53 of i t s difference of 16 mass units from the proposed macro-cycle ( i . e . exactly the mass of one atom of oxygen). In l i g h t of the new knowledge, i t was r e a l i z e d that the product could be one a r i s i n g from the 3 + 2 condensation whereby the t r i -pyrrane (34) and dipyrrane (48) condensed at one end to form a l i n e a r pentapyrrole (62a) but, rather than c y c l i z e at the other terminus, the acid f u n c t i o n a l i t y attacked at the bridge p o s i t i o n (see Scheme 11), despite the e f f e c t of the electron-withdrawing ester,creating a meso-substituted porphodimethene (62), which on oxidation with DDQ resulted i n the f i n a l meso-substituted porphyrin (63) . The s t a b i l i t y of the proposed product was evidenced i n i t s mass spectrum. Porphyrins - are very stable i n the mass spectrometer and generally show two peaks,, one corresponding to the parent at m/e (often the same as the base peak) and another at m/2e corresponding to the doubly charged species. Four such peaks were found i n the mass spectrum of our compound: m/e 657 and m/2e 378.5 corresponding to the whole molecule and m/e 535 and m/2e 267.5 corresponding to a stable species (undoubtedly a porphyrin) formed from the parent compound afte r the loss of 122 mass units (i.e."the loss of the meso py r r o l e ) . Also a re-examination of one of our previous high resolution mass spectra, which had been taken of a compound exhib i t i n g m/e 647 as the parent peak, was found to have i n fa c t , m/e 657 as the parent peak, and a computer-generated possible chemical composition for that peak was 54 SCHEME II 55 C41 H47 N5°3' e x a c t l y that f o r our proposed product (63). An i n f r a r e d spectrum (I.R. #1) i n chloroform solution showed two carbonyl stretching frequencies at 17 02 cm 1 (the ester) and 1635 cm 1 (the aldehyde), which further corroborated the proposed structure for our product. The pentapyrrolic macrocycle, i f formed, or the porphyrin (59) , would only have one carbonyl. As previously mentioned, the v i s i b l e spectrum resembled that of a porphyrin which, on the addition of acid was converted to a p h l o r i n - l i k e pattern (spectrum of the p h l o r i n (63a)) and returned to the c h a r a c t e r i s t i c porphyrin shape on the addition of base. To authenticate the proposed pro-tonation/deprotonation mechanism (rather than another mechanism involving attack by only strong nucleophiles, such as t r i e t h y l -amine) a quantity of the product i n methylene chloride was a c i d i f i e d with t r i f l u o r o a c e t i c acid and nucleophiles of varying strengths (Proton Sponge, 1,5-Diazabicyclo [5.4.0] undec-5-ene (DBU), pyridine, triethylamine) were added i n an attempt to regenerate the o r i g i n a l spectrum. The fact that even the weakest nucleophile (aqueous sodium bicarbonate, shaken with the methylene chloride solution of the proposed phlorin) re-generated the porphyrin spectrum was taken as conclusive proof that a simple protonation and deprotonation was taking place. There remained but to obtain an nmr to determine i f there were, i n f a c t , only three meso protons. This involved 56 r e p e t i t i o n of the experiment with oxidation of the mixture immediately a f t e r the f i r s t observation of the 488 nm. band i n the v i s i b l e spectrum ( i f one waited u n t i l the 488 nm. band became too large, none of the desired product (meso-substituted porphyrin) was obtained). The nmr (NMR #10, i n CDCl^) was quite conclusive with regard to the structure of our com-pound. I t did show only three meso protons f a r downfield (at 6(ppm): 11.17, 11.10 and 10.93) due to the deshielding by the r i n g current and, i n f a c t , one of those protons (10.93 ppm) was s l i g h t l y farther u p f i e l d ( i . e . , more shielded), noticeably separate from the other two, c h a r a c t e r i s t i c of a meso proton opposite a meso substituent. The spectrum also exhibited signals for methyl substituents (6(ppm) 2.87 and 2.65) at higher f i e l d than observed f o r methyls on the porphyrin (3.62 ppm) and i n d i c a t i v e of t h e i r being more shielded and hence on the meso pyrrole. One could also see the s i n g l e t at 11.88 ppm f o r the p y r r o l y l aldehyde proton, multiplets at 5.8 6 and 4.04 ppm corresponding to the^methylene groups of the ethyl ester and ethyl substituents on the porphyrin and at ^1.86 and 1.64 ppm for the corresponding methyls of ethyl groups. 3.1.3 Conclusions When the project was begun i t was assumed that the ethyl ester on the c e n t r a l pyrrole would be s u f f i c i e n t l y electron-57 withdrawing so as to prevent coupling to at l e a s t one meso po s i t i o n . Hence one could predict that there was equal pro-b a b i l i t y of c y c l i z a t i o n at the terminus of the tripyrrane as at the meso p o s i t i o n (on the side opposite the deactivating e s t e r ) . This does not seem t o have been the case. A l l recent r e s u l t s indicate that only porphyrins are formed v i a the condensation and there i s no compelling evidence for the f o r -mation of. a pentapyrrolic macrocycle. I t would appear that the electron-withdrawing a b i l i t y of the ester moiety was i n -s u f f i c i e n t to prevent porphyrin formation. I t seems too, i n l i g h t of the almost exclusive formation of porphyrins ((59) or (63)), that the r i n g closure r e s u l t i n g i n a porphyrin i s much more favored than any other c y c l i z a t i o n . This would i n d i -cate that despite a l l our e f f o r t s to make the system electron-i c a l l y disfavorable toward attack at the bridging methylene we could s t i l l not overcome the large s t e r i c and thermo-dynamic e f f e c t s promoting porphyrin formation. I t had been s t a t e d 1 1 that a model of the proposed f i n a l product macro-cycle (15) had been made and found to be strained but s t i l l f e a s i b l e . We made models (using the s p a c e - f i l l i n g (CPK) type) of both the proposed macrocycle (15) which we found to be very strained and of i t s precursor (62a). The l i n e a r pentapyrrole (62a) quite n a t u r a l l y assumed a s p i r a l shape with the terminal pyrroles situated above one another i n the i d e a l p o s i t i o n for attack at the bridging carbon. A model of the s i m i l a r l i n e a r 58 pentapyrrolic precursor for decamethylsapphyrin (11) (the macrocycle being a known compound) was also b u i l t , but i n that case, the terminal pyrroles were not so i d e a l l y situated. The shorter o v e r a l l length (one carbon atom shorter than (62a) and the d i r e c t l i n k between two pyrroles (imparting some r i g i d i t y to the l i n e a r system) could have caused the termini of the sapphyrin precursor to have been i n more intimate association with one another rather than one terminus with a bridging carbon and hence allowing the formation of sapphyrin rather than a meso-pyrrolyl c o r r o l e . with the B-ester and the meso-pyrrole separated by a 8-methyl substitutent. Another possible c y c l i z a t i o n i s that involving coupling at the opposite termini i n i t i a l l y , r e s u l t i n g i n the other isomer (64), with the B-ester adjacent to the meso-pyrrole. Without more data we cannot d e f i n i t i v e l y state that the struc-ture of our compound was (63) but, because of the weaker s t e r i c s t r a i n i n (63) we f e e l i t i s more l i k e l y the structure than We have given the structure of our product as (63), (64) . (63) (64) 59 Our proposed mechanism for porphyrin, rather than pentapyrrolic macrocycle, formation would also serve to explain the frequent observation of the porphyrin (59) with m/e 536. I f , i n f a c t , a meso-pyrrolyl porphyrinogen or porpho-dimethene (as (62)) were formed f i r s t , non-specific oxida-tions (via l i g h t , oxygen or on the chromatography plate) could have been assumed to have formed the most stable porphyrin i . e . (59) as the bulky meso-substitutent would have been l o s t . However, oxidation with DDQ, which during the reaction i s converted to 2,3-dichloro-5,6-dicyano-l,4-hydroquinone, involves s p e c i f i c a l l y the loss of hydrogen thereby trapping the pyrrole as the meso substitutent. Were the DDQ oxidation to have been done a f t e r chromatography, i t i s u n l i k e l y that any of the f i n a l product (63) would have been found as the pro-b a b i l i t y i s high that the pyrrole substituent would have long since been excised. The i d e n t i t y of the compound with m/e 647 i s s t i l l unclear. I t seems reasonable to assume that i t too was a meso p y r r o l y l porphyrin precursor (such as a porphyrinogen) which would r e a d i l y rearrange to form the stable porphyrin (59) (as evidenced by the usual presence of m/e 536 as the base peak i n the mass spectrum). However, one p o s s i b i l i t y for that compound, which f u l f i l s the requirements of: a mass of 647, and i t s being a precursor for porphyrins, would be (65), a species which may,however, be u n l i k e l y to survive chromatography l e t alone 60 i s o l a t i o n because of the natural tendency of most porphyrinogens not to suffer such i n d i g n i t i e s . The mechanism of formation of a species such as (65) i s unclear but with the addition of water, followed by oxidation, i t could be converted to the meso-pyrrolyl porphyrin (63). I t appears from these findings that the preparation of a pentapyrrolic macrocycle analogous to porphyrin, i f i t i s even possible, i s much more d i f f i c u l t than o r i g i n a l l y envisaged. A route may be found i f some method were discovered of deactivating both bridging positions simultaneously and s u f f i c i e n t l y to force a l i n e a r pentapyrrole to c y c l i z e . S i m i l a r l y substituted meso-pyrrolyl porphyrins have 4 9 been found i n another system. Clezy and co-workers prepared (67) from hexapyrrene (66) v i a the action of cupric acetate acetate i n pyridine (Scheme 12). Their compounds exhibited nmr chemical s h i f t s for meso protons and p y r r o l y l methyl substituents and e l e c t r o n i c spectral changes i n acid very s i m i l a r to those shown by (63) and the structure of t h e i r meso-pyrrolylporphyrin was confirmed by combustion and mass spectroscopic analysis. 61 It i s also i n t e r e s t i n g to note that i n Woodward and 2 Bauer's synthesis , they proposed a meso p y r r o l y l porphyrin struc-ture for t h e i r compound a f t e r t h e i r supposed corrole was 4 disproved by Johnson and Kay . The basis for Woodward and Bauer's proposal was the f a c i l e loss of a pyrrole unit in the mass spectrum. Only more complete nmr analysis led them to propose the penta-p y r r o l i c macrocyclic structure of sapphyrin (9). We, on the other hand, i n our attempts to prepare a pentapyrrolic macrocycle, have come f u l l c i r c l e and have prepared the com-pound postulated by Woodward so long ago. Under the reaction conditions employed and allowing for fragmentation reactions we can envisage the three mecha-n i s t i c routes shown i n Scheme 13. We had hoped the c y c l i z a t i o n would occur v i a 13A which would r e s u l t i n the pentapyrrolic porphyrin analogue (15). The mechanisms shown i n 13B and 13C appear, however, to have been the dominant ones. Route 13B, involving the formation of a pyrromethene bridge by a i r oxidation of (62a), would r e s u l t i n the synthesis of our meso-pyrrolyl porphyrin (63). The loss of a terminal p y r r o l i c unit as shown i n Route 13C would r e s u l t i n the f o r -mation of the other porphyrin we observed, (59). 62 63 (59) 64 3.2 Sapphyrin The reaction to prepare sapphyrin (16) was ca r r i e d 10 7 out according to the methods of King and Wang as depicted on Scheme 14. The coupling, l i k e that for decamethyl-sapphyrin (10), was done at high d i l u t i o n to minimize i n t e r -molecular polymerization and at room temperature to prevent 65 random fragmentation. The bipyrrole dialdehyde (58) was dissolved i n ethanol and the r e q u i s i t e amount of tripyrrane 50 d i a c i d (31) stock solution was added to the s t i r r i n g mixture No attempt was made to protect the reaction mixture from l i g h t . The solution remained e s s e n t i a l l y c o l o r l e s s (the bipy r r o l e dialdehyde imparted some of i t s yellow color to the ethanolic solution) u n t i l the p-toluene-sulfonic acid was added, a f t e r which the solution became dark yellow then dark red, over 30 seconds. An a i r stream was introduced immediately to complete the oxidation. After 10 min. the mixture was dark red-brown and, a f t e r 30 min. had become dark green (the c h a r a c t e r i s t i c color for sapphyrin i n s o l u t i o n ) . No further color changes were observed and the solution was l e f t s t i r r i n g with the a i r stream overnight. The v i s i b l e spectrum of the reaction solution was of s i m i l a r shape to that shown by K i n g 1 0 (Spectrum #4) (X (nm.) 431 (sh), 456 (Soret), in 3.x 578, 631, 689, 723). A check, by thin layer chromatography, showed more than one compound present so the ethanol solution was mixed with an equal volume of r e - d i s t i l l e d methylene chloride and the acid was extracted with three volumes of water. The organic phase was dried and evaporated i n vacuo to dryness. The residue was dissolved in fresh methylene chloride and chromatographed on a preparative plate. A dark green band (the low r . f . (0.1-0.2) being the chief reason column chromato-graphy was not used) present a f t e r chromatography was obviously 66 •the desired product. The band was scraped from the plate and the compound eluted from the s i l i c a gel with methylene-chloride/methanol (1:1). A v i s i b l e spectrum of the compound in the solvent system revealed: (X (nm.) 423 (shoulder), in 3.x 447 (Soret), 578, 620, 679, 713 (Spectrum #4). Mass spectral analysis afforded a spectrum with: parent peak = 575, rather than 573, the expected molecular weight of the compound. This high m/e was not surprising as sapphyrins are r e a d i l y pro- • tonated. Even traces of methanol, which may have been present 7 10 i n the sample, could protonate the macrocycle ' Attempts to r e c r y s t a l l i z e the sapphyrin resulted i n decomposition. Whether the macrocycle was unstable with r e -spect to the heat, the solvent or even the f i n a l drying i n  vacuo i s unknown. The decomposition product whose v i s i b l e spectrum was very much l i k e that of the crude reaction mixture U (nm.), 431, 456 (Soret), 578, 628, 689, 723) had a l u 3 X parent peak (in the mass spectrum) with m/e = 718 (probably r e s u l t i n g from recombination of the cleaved pentapyrrolic r i n g to p o l y - p y r r o l i c polymers). It was also found that f a i l u r e to remove the p-toluene s u l f o n i c acid p r i o r to concentration of the crude reaction mixture for chromatography resulted i n decomposition of the macrocycle, probably v i a cleavage and acid-catalysed recombination reactions. 67 We attempted to i n s e r t a cation into the sapphyrin with 2+ 29 uranyl chloride. The uranyl cation (UC^ ) was known to coordinate f i v e ligands about i t i n a plane and the synthesis of the uranyl decamethylsapphyrin had been unsuccessfully 7 attempted previously by S-W. Wang . The most probable cause for the f a i l u r e was the fact that uranyl acetate (found as U 0 2 (°2 C C H3^ 2* 2 H 2 ° ^ W a S t* i e compound used. In coordination to a metal, competition between the ligands for coordination s i t e s i s very important. Obviously i t i s desirable to have the ligand you want coordinated more strongly to the metal ion than the counter ion from the metal s a l t , and i n uranyl acetate the water of hydration (a strongly coordinating ligand) occupies two of the coordination s i t e s . For that reason we chose uranyl chloride (U0 2C1 2), which was anhydrous, for our attempts. As the metal s a l t was both hygroscopic and absorbed carbon dioxide r e a d i l y , a l l the operations with i t had to be c a r r i e d out i n an i n e r t (nitrogen) atmosphere in a dry box and a l l solvents were dried and degassed. Finding an appropriate solvent for the reaction was the f i r s t obstacle as the uranyl chloride had no^ or l i m i t e d s o l u b i l i t y i n most of the organic solvents which dissolved the sapphyrin; (e.g., insoluble i n methylene chloride and ether, poorly soluble i n pyridine and a c e t o n i t r i l e and soluble i n methanol and ethanol due to the traces of water present i n the alcohols,which solvated the metal compound). N,N-dimethyl-acetamide ( r e d i s t i l l e d from calcium hydride) was determined 68 to be the solvent of choice. The use of N,N-dimethylformamide was rejected on two counts: (a) the solvent was d i f f i c u l t to dry and p u r i f y and keep dry and pure, and (b), the amine impurity i n i t was thought to f a c i l i t a t e degradation of the 7 macrocycle v i a some r e v e r s i b l e reaction . As metallation reactions, for porphyrins, normally require heating of a solution of the porphyrin and metal s a l t i n a suitable solvent we surmised (and were l a t e r supported by facts) that the coordination of our sapphyrin would not occur at room temperature. We then attempted to force the i n s e r t i o n i n a sealed tube at temperatures i n the range of 200°. The uranyl chloride sapphyrin and solvent were placed i n a t h i c k -walled tube i n an i n e r t , dry atmosphere and sealed with a rubber septum. The vessel was attached to a vacuum l i n e by a needle through the septum and the solution was degassed twice by freeze, pump and thaw cycles. The sample was f i n a l l y sealed i n the tube, under vacuum, while frozen. After thawing, the sealed tube was placed i n an oven and was heated at ^ 2 00°C for 16 hours. When removed from the tube we found the physical properties of the sapphyrin solution had changed. The col o r , o r i g i n a l l y a dark green, was green-brown and the bands i n the uv-vis spectrum had s h i f t e d . Hopeful that coordination had occurred, we examined more c l o s e l y the v i s i b l e spectrum. I t was found that the bands i n the spectrum (which looked suspiciously l i k e unmetallated sapphyrin) were almost exactly those of our 69 previously mentioned decomposition product ( i . e . , A (nm.), ITlclX 431 (sh), 456 (Soret), 578, 628, 689, 723). We found too that a sample of our prepared sapphyrin (16) i n N,N-dimethyl-acetamide changed from green to a brown color when s i t t i n g i n l i g h t . Examination of i t s v i s i b l e spectrum revealed that the sample was undergoing conversion to the decomposition product. I t i s believed that perhaps traces of an amine impurity i n the 7 DMA caused t h i s change. Wang noted that triethylamme caused a change i n decamethyl sapphyrin (11) i n solution i n methanol which was reversed by the addition of base. The change, evidenced by the loss of color of the sapphyrin solution was surmised to be a break i n conjugation of the sapphyrin system by the triethylamine. Our change i n reaction mixture was not r e v e r s i b l e and because of these r e s u l t s we assumed that the sapphyrin had, i n f a c t , not been coordinated. In fa c t the spectrum of the "decomposition product" (formed i n DMA) was very s i m i l a r to that for decamethylsapphyrin (11) (for decomp. product A (nm.): 431, 456 (Soret), 578, 628, 689, 723, for ITlclX (11) A : 431, 456.5 (Soret), 579, 625, 677, 689) which suggested that perhaps only minor modifications to the p e r i -phery of the r i n g ( i . e . loss of, or a reaction at the ester f u n c t i o n a l i t y ) had taken place. Here too, because only minute amounts of the product were made i t was not characterized further. I t i s s t i l l believed that our sapphyrin ought to undergo coordination. Perhaps someone whose expertise i n that area i s 70 greater than mine w i l l accomplish i t . Having shown, at le a s t , that the sapphyrin (16) could be prepared we turned our attention to the other macrocyclic systems. 3.3 Superphthalocyanine Superphthalocyanine (17) was prepared by the method 28 of Bloor et a l . In 1964 they had prepared what was thought, on the basis of spectral data and what turned out to be a poor combustion analysis, to be uranyl phthalocyanine (17, M = U0 2). Day, Marks and Wachter 2 9, i n 1974, reported a r e p e t i t i o n of t h i s synthesis and, based on a better combustion analysis and a c r y s t a l structure, showed the compound to be the uranyl moiety coordinated to f i v e phthalocyanato ligands i n a plane about i t . Hence the term 'superphthalocyanine'. We prepared t h i s compound for eventual comparison (of reac-t i v i t y , metallation and demetallation properties, s t a b i l i t y , etc.) with our sought a f t e r macrocycle and prepared sapphyrin. The synthesis was r e l a t i v e l y simple (involving a short relux, p r e c i p i t a t i o n of the crude products aand extraction of the pure product from the mixture) but unsatisfactory due to the poor s o l u b i l i t y of the f i n a l product (17) i n most common organic solvents. The 1,2,4-trichlorobenzene (b.p. 213°), necessary for the extraction of the pure macrocycle from the mixture, and a-chloronapthalene (b.p. 256°) , used as 71 the solvent for the v i s i b l e spectrum are neither common solvents nor could the product be e a s i l y recovered from them 2 8 Lack of d e t a i l i n the published workup procedure resulted i n our product being contaminated with phthalocyanine (68) (we had extracted the crude product mixture too long with the trichlorobenzene) and t h i s was detected i n the v i s i b l e spectrum. (68) An infrared spectrum (KBr disk) served to corroborate our spectral data as the i r was comparable band for band with 28 29 published spectra ' . As the time needed for the reaction was very short (30 min.) and because the reaction could be scaled up quite e a s i l y (the precursor i s r e a d i l y a v a i l a b l e ) , s u f f i c i e n t quantities of the uranyl-superphthalocyanine could r e a d i l y be prepared for more thorough studies ( i . e . demetallation, r e a c t i v i t y , e t c . ) . 72 3.4 Superbenzporphyrin Because of the ease of preparation of the 'super-phthalocyanine' we postulated the formation of a 'supar-benzporphyrin' (18) i n a l i k e manner. The compound ought to provide a l i n k between the proposed superporphyrin (15) and the superphthalocyanine (17). Tetrabenzporphyrins (as i n Scheme 16) are normally prepared"'"*' by sealing the isoindole precursor (70) and the metal s a l t i n a thick-walled tube and heating i n an oven at 4 00°C for several hours. The metallotetrabenzporphyrins are re-covered i n high y i e l d from the mixture of crude products b y soxhlet extraction with pyridine. We attempted to u t i l i z e t h i s procedure i n the pre-paration of uranylpentabenzporphyrin (see Scheme 15) . Isoindole 52 acetic acid (69) (used as the precursor rather than 1,3,4,7-tetramethylisoindole), and uranyl chloride were reacted two d i f f e r e n t ways: the f i r s t mimicing the published pro-cedure (conditions A i n Scheme 15) the second, a s l i g h t modification (conditions B i n Scheme 15). Because we were unsure of the p u r i t y ( i . e . dryness) of the precursor (69), a two-fold excess of the metal s a l t was used i n both cases. When sealing reactants i n the thick-walled tubes, care was taken that no s o l i d remained on the c o n s t r i c t i o n where the tube was to be sealed. This would cause a weak 73 H ;CH2COOH SCHEME 15 A + UC^-Superbenzporphyr B ? (18) °(69) Reaction Conditions A. No solvent , 4 0 0 ° , sealed tube B. «-Chloronapthalene , 4 0 0 ° , sealed tube seal to be formed and could lead to the destruction of the tube (on more than one occasion our tubes exploded i n the oven because of weak se a l s ) . A reaction under conditions A above (i . e . no solvent) resulted i n the production of a tube f u l l of charred material which, when extracted with pyridine, relinquished no superbenzporphyrin or tetrabenzporphyrin. Another reaction, with a high b o i l i n g solvent (conditions E above) resulted i n an explosion of the tube - the solvent (boiling point 256°) creating more pressure (at 4 00°) than the tube was able to withstand. Extraction of the glass fragments (to which some blackened organic material had adhered) with pyridine also produced no evidence of product (18) formation. correct conditions for a successful reaction as our studies have only shown that 'superbenzporphyrin' (18) i s not formed under the conditions used for tetrabenzporphyrin Further studies are necessary to determine the 7 4 production. It was noted i n a report by Bender, Bonnett and Smith" 5 1 that octamethyltetrabenzporphyrin-bis-pyridine complex (71) could be prepared from 1,3,4,7-tetramethylisoindole (70) and magnesium acetate (Scheme 16) by r e f l u x i n g i n 1,2,4-trichlorobenzene (b.p. 256°) under an atmosphere of oxygen-free nitrogen. This method may be worthy of future study i n t h i s instance. SCHEME 16 Me Me A a Me, Me1- 'Me M e (70 ) (71) 75 4. EXPERIMENTAL As none of the coupling components required for these studies were commercially avai l a b l e , a l l of the necessary compounds had to be prepared from monopyrroles which had 53 been synthesized e a r l i e r Melting points (when taken) were obtained on a Thomas Hoover Unimelt, a capillary/oil-immersion apparatus and the r e s u l t s are presented uncorrected. The i r spectra were taken on a Perkin Elmer 457 (grating) recording spectrophotometer. The nmr spectra were usually run on the Varian T-60. For spectrum #10 the Varian XL-100 (a Fourier transform instrument) was used because of the small quantity. The mass spectra were obtained on the departmental MAT CH4 B instrument, using the d i r e c t i n s e r t i o n method and an electron energy of 7 0 eV. V i s i b l e and u.v. spectra were taken on the group CARY-17 Recording Spectrophotometer. As the spectra were generally obtained for q u a l i t a t i v e analyses, they were referenced against a i r . The most common method of chromatography was on preparative plates using those produced by Analtech ( S i l i c a Gel GF (fluorescent indicator added), 2000 u thickness, 20 x 20 cm. area). Analtech 2.5 x 10 cm. x 250 u (thickness) 76 S i l i c a Gel GF plates were used for th i n layer chromatography. For column chromatography, Woelm S i l i c a Gel G, a c t i v i t y II or IV was used. 77 0 2-Carbobenzyloxy-5-Chloromethyl-3,4-dimethylpyrrole 2-Carbobenzyloxy-3 , 4 , 5-trimethylpyr.role (2 8) (24,3g, 0.1 mole) was suspended i n 250 ml. dry d i e t h y l ether under a dry, i n e r t atmosphere and s t i r r e d at room temprature. A solution of s u l f u r y l chloride (13.8g, 8.3 ml., 0.1 mole = 13.5g) i n carbon t e t r a c h l o r i d e (20 ml., Spectral grade) was added dropwise over a 15 min. period. With the i n i t i a l addition of s u l f u r y l chloride the c o l o r l e s s solution of trimethylpyrrole turned yellow and a l l the s t a r t i n g material dissolved. A f t e r half of the s u l f u r y l chloride had been added, white product began to p r e c i p i t a t e u n t i l the solution was thick. A f t e r the addition was complete, the mixture was s t i r r e d f o r a further 45 min. and the product was f i l t e r e d o f f and rinsed with ether and hexane. The y i e l d of snow-white c r y s t a l s was 12.4g (44.75%) and was stored i n a foil-wrapped bo t t l e to prevent decomposi-t i o n . Poor s o l u b i l i t y prevented analysis by nmr. 78 2,5-Bis-(5-carbobenzylexy-3,4-dimethyl-2-pyrrolylmethyl)-3-carbethoxy-4-methylpyrrole 2-Carbobenzyloxy-5-chloromethyl-3,4-dimethylpyrrole (29) (12.4g, 0.0446 moles) and 3-carbethoxy-4-methylpyrrole (27) (3.41g, 0.0223 moles) were dissolved i n 60 ml. reagent grade methylene chloride and, with s t i r r i n g , the solu t i o n was boiled down to a small volume. Hydrogen chloride was evolved and the solution turned dark burgundy red. At the cessation of HC1 evolution 50 ml. of methanol (reagent grade) were added and the b o i l i n g was continued to drive o f f the methylene chloride. When cooled, the very f i n e p a r t i c u l a t e product p r e c i p i t a t e d from the solution, was f i l t e r e d and washed with methanol (tot a l volume of f i l t r a t e s and washings was 200 ml.). The crude material (wet wt. 13g) was a mixture of the product (30) and biproduct 5,5'-dicarbobenzyloxy-3,3',4,4*-tetramethyl-2,2'-dipyrromethane. The mixture was dissolved i n 50 ml. of methylene chloride and d i l u t e d with hot petroleum ether (b.p. 60-110°) causing the dipyrromethane to c r y s t a l l i z e . The solu t i o n was cooled i n the r e f r i g e r a t o r to complete the c r y s t a l l i z a t i o n , was f i l t e r e d and the byproduct rinsed with more petroleum 79 ether ( y i e l d of biproduct = 0.8315g). The f i l t r a t e s and washings, which were a pale pink-range color, were evaporated to dryness and the r e s u l t i n g colored s o l i d s redissolved i n 25 ml. of tetrahydrofuran. The solution was heated to b o i l -ing and the tetrahydrofuran was displaced by methanol. Once again the product c r y s t a l l i z e d (as pink-orange granules). The solution was cooled, f i l t e r e d , the c r y s t a l s were washed with methanol.and a i r dried overnight. The f i n a l y i e l d was 5.983g (42.22%). NMR: #1 (CDC13) (ppm) #H shape J(Hz) 1.38 3 t 7-7.5 1.75 3 s 1.95 3 s 2.22 3 s 2.27 6 s 3.41 2 bs 4.1-4.6 8 complex (4.37) (2) (q) (7-7.5) 6.9-7.15 10 complex m (7.25 i n t a l l e s t peak) 9.71 1 bs 11.11 1 bs 11.16 1 bs 80 (a) Tripyrrane diacid;2,5-Bis-(5-carboxyl-3,4-dimethyl-2- pyrrolylmethyl)-3-carbethoxy-4-methylpyrrole (31) (2,5-Bis-(5-carbobenzyloxy-3,4-dimethyl-2-pyrrolyl-methyl)-3-carbethoxy-4-methylpyrrole (30) (1.3204g, 0.00208 moles) was dissolved i n 100 ml of fresh tetrahydrofuran and added to 10% Pd/C c a t a l y s t . The solution was s t i r r e d under an hydrogen atmosphere overnight (uptake = 100 ml., t h e o r e t i c a l = 93.2 ml.). The solution was then f i l t e r e d to remove the ca t a l y s t , which was washed with fresh THF, and the f i l t r a t e s and washings were evaporated to dryness i n vacuo. The product was weighed i n the flask then quickly redissolved i n a measured amount of THF and stored i n the r e f r i g e r a t o r i n the dark. NMR: #2 (DMSO-D,.) 6 (ppm) #H shape J(Hz). 1.26 t 7-7.5 1.39 b s 1.77 6 s 2.14 6 s (2.48 DMSO-Residue) (3.38 broad multiplet impurity) 3.66 2 s 4.08 2 s 4.13 2 q 7-7.5 6.45 1 s 81 6(ppm) #H shape J(Hz) 6.80 1 s 10.30 1 bs 10.48 1 bs 10.63 1 bs (b) Tripyrrane dialdehyde:2,5-Bis-(5-formyl-3,4-dimethyl-2- pyrrolylmethyl)-3-carbethoxy-4-methylpyrro.le (34) For conversion to the dialdehyde, a l l of the THF solution containing the d i a c i d from part (a) was evaporated to dryness i n vacuo. Three successive 5 ml. N,N-dimethyl-formamide extracts of the r e s u l t i n g grey-green d i a c i d s o l i d s were added to r e f l u x i n g (under nitrogen) DMF (5 ml.) i n a 50 ml. Erlenmeyer f l a s k (with a standard taper 14/23 neck and equipped with a Claisen adapter on the side arm and a ref l u x condenser above i t ) . The solution became reddish-brown and was refluxed for 4 0 min. then c h i l l e d i n an i c e bath. To the cold DMF solution ( s t i l l under nitrogen) was added a solution of 2.Og (1.64 ml.) of benzoyl chloride i n DMF (5 ml.). The solution became darker red and was stoppered and allowed to s i t on the bench overnight during which time the gelatinous p r e c i p i t a t e of the iminium s a l t (33) came out of solution. Diethyl ether (60 ml., anhydrous) was added, causing further p r e c i p i t a t i o n of the s a l t . The p r e c i p i t a t e was f i l t e r e d , washed with more ether, a i r dried then dissolved 82 i n a minimum of d i s t i l l e d water with warming and the hot solu-t i o n was f i l t e r e d to remove traces of the Pd/C c a t a l y s t . Sodium bicarbonate (^lg.) was added to the hot reddish-brown solution r e s u l t i n g i n the formation of a v i s -cous c o l l o i d a l suspension which coagulated into l i g h t brown or tan colored chunks when the solution was heated to b o i l i n g . The s o l i d s were f i l t e r e d from the solution, washed well with d i s t i l l e d water and r e c r y s t a l l i z e d from methylene c h l o r i d e / methanol (15-20 ml.) by displacement and were f i l t e r e d and a i r dried. The y i e l d of tripyrrane dialdehyde (34) was 0.2400 g. (28.77%). NMR: #3 (CDC13) MP: 219-220° (uncorr.) L i t 1 1 : 221-221.5 (uncorr.) 6 (ppm) . #H shape J(Hz) 1.36 3 t 7-7.5 1.95 6 s 2.18 6 s 2.28 3 s 3.72 2 s 4.27 4 7-7.5 8.82 1 s 8.85 1 s 10.05 1 bs 10.92 1 bs 11.09 1 bs 83 2-Carbobenzyloxy-3,4-diethyl-5-methyl pyrrole 2-Carbethoxy-3,4-diethyl-5-methylpyrrole (43) (40.Og., 0.193 moles) was dissolved i n 80 ml of r e d i s t i l l e d benzyl alcohol and heated to r e f l u x under nitrogen i n a 125 ml. Erlenmeyer f l a s k equipped with a Claisen adapter with a nitrogen i n l e t on the side arm and a r e f l u x condenser above. A few drops of sodium benzyloxide. c a t a l y s t (prepared by d i s s o l v i n g sodium metal i n benzyl alcohol) were added to the r e f l u x i n g s o l u t i o n causing a temperature drop and the evolu-t i o n of ethanol vapours. When the reaction subsided more ca t a l y s t was added. The procedure was repeated u n t i l no further reaction was observed and the temperature of the r e f l u x i n g solution was again that of benzyl alcohol (209°). The hot solution was then poured into a quenching mixture of methanol (300 ml.) d i s t i l l e d water (300 ml.) and g l a c i a l a c e t i c acid (10 ml.) to cause p r e c i p i t a t i o n . At t h i s point the cl e a r pale yellow solution turned pink and a white granular material p r e c i p i t a t e d from the solution and the suspension was allowed to s i t overnight. The product (45) was f i l t e r e d , washed with d i s t i l l e d water (200 ml.) and methanol (200 ml.) and a i r dried. 84 The y i e l d of crude product was 24.0 g (46.4%) which the nmr i n d i c a t e d was pure enough to use without r e c r y s t a l l i z a t i o n . NMR: #4 (CDC13) MP: 72-73° (uncorr.) L i t 1 1 : 72-73° (uncorr.) 6(ppm) #H shape J(Hz) 1.06 3 t 7-7.5 1.12 3 t 7-7.5 2.15 3 s 2.36 2 q 7-7.5 2.66 2 q 7-7.5 5.14 2 s 7.30 5 s 8.89 1 bs 85 o H o (4 6 ) 5-Acetoxymethyl-2-carbobenzyloxy-3,4-diethylpyrrole 2-Carbobenzyloxy-3,4-diethyl-5-methylpyrrole (45) (27.1 g., 0.1 moles) was dissolved i n 100 ml. of g l a c i a l a c e t i c acid and to the solution was added 48 g. (an excess) of lead tetraacetate a l l at once. The mixture was swirled manually and monitored by t i c (monitoring disappearance of s t a r t i n g material). More lead tetraacetate (10 g.) and heating (no higher than 30°C) were required to complete the reaction. The product carboxylate (4 6) p r e c i p i t a t e d from the a c e t i c acid of i t s own accord and ethylene g l y c o l (^ 5 ml.) was added to reduce any remaining lead (IV). D i s t i l l e d water (300 ml.) was added to d i l u t e the reaction mixture which was then f i l t e r e d , the ppt was washed with more d i s t i l l e d water (300 ml) and a i r dried. The wet product was not weighted (but t i c showed only one spot, that of the product) and because of i t s poor s o l u b i l i t y was not analysed by nmr. I t was used, i n i t s e n t i r e t y , f o r the next step. 86 5,5'-Dicarbobenzyloxy-3,3',4,4'-tetraethyl-2,2'-dipyrromethane The entire wet y i e l d of 5-acetoxymethyl-2-carbo-benzyloxy-3,4-diethylpyrrole (4 6) from the previous reaction was dissolved i n methylene chloride, separated from the water (using a separatory funnel) and the organic phase was evaporated to dryness i n vacuo. The s o l i d s were redissolved i n 150 ml. of 95% ethanol and heated to b o i l i n g . HC1 (concentrated, 1 ml.) was added and b o i l i n g was continued for 1 hr. The f l a s k was l e f t to cool overnight during which time the crude product c r y s t a l l i z e d . The impure c r y s t a l s were crushed i n sol u t i o n , f i l t e r e d and washed with ethanol y i e l d i n g 15.2545 g. Re-c r y s t a l l i z a t i o n from methylene chloride/methanol by disp l a c e -ment produced 13.8471 g. (52.5% o v e r a l l , from (4 5)) of pure product (47). NMR: #5 (CDC1 ) MP: 119-120° (uncorr.) J L i t 1 1 : 119.5-120.5 (uncorr. 6(ppm) #H shape J (Hz) 1.02 6 t 7-7.5 1.10 6 t 7-7.5 2.38 4 q 7-7.5 2.68 4 q 7-7.5 3.75 2 s 5.16 4 s 7.21 10 s 9.08 2 bs 87 151) (a) Dipyrrane diacid:5,5'-dicarboxy-3,3',4,4'-tetraethyl-2,2'-dipyrromethane 5,5'-Dicarbobenzyloxy-3,3 ' , 4 , 4 1-tetraethyl-2,2 * -dipyrromethane (47) (5.304 g. , 0.0101 moles) was dissolved i n a suspension of 10% Pd/C i n 100 ml. of tetrahydrofuran and s t i r r e d under an hydrogen atmosphere for 5 hr. (uptake was 500 ml., t h e o r e t i c a l uptake = 451 ml.). The s o l u t i o n was f i l t e r e d to remove the Pd/C, the c a t a l y s t was washed with more tetrahydrofuran and the f i l t r a t e s and washings were combined and evaporated to dryness (Rotovap). As the product d i c a r -boxylic acid (48) was very unstable, the residue was weighed when dry then redissolved i n a known quantity of THF (to accurately determine the concentration) and stored i n a t i g h t l y stoppered brown bo t t l e i n the r e f r i g e r a t o r . Lack of s o l u b i l i t y i n any common deuterated solvent precluded analysis by nmr. 88 (b) Dipyrrane dialdehyde:5,5'-diformyl-3,3',4,4'-tetraethyl- 2,2'-dipyrromethane For conversion to the dialdehyde, the ent i r e THF solution of the d i a c i d (48) from part (a) was evaporated to dryness i n vacuo. The grey-green crusts of the d i a c i d (5.255 g., 0.0116 moles) was dissolved i n DMF (20 ml.) and heated to b o i l i n g under a stream of nitrogen. The solu t i o n changed from dark green at the outset to dark red-brown at the conclusion of a 30 min. r e f l u x . The f l a s k was then cooled i n i c e and, s t i l l under nitrogen, benzoyl chloride (6.0 g. , 6.2 ml., 0.0427 moles) was added, causing the solution to turn red i n addition to p r e c i p i t a t i o n of the di-iminium s a l t (50). The suspension sat at room temperature for 9 hr. The thick p r e c i p i t a t e was d i l u t e d with DMF, f i l t e r e d , washed with more N,N-dimethylformamide and ether and a i r dried overnight. The di-iminium s a l t (50) was then dissolved i n a minimun volume of d i s t i l l e d water, f i l t e r e d to remove traces of Pd/C and other insolubles and heated i n a steam bath. The aqueous solution was b a s i f i e d with potassium car-borate (^ 1 g.) causing a brown o i l to separate. The o i l soon s o l i d i f i e d (brown granules) and the solution became cl e a r . The crude product was f i l t e r e d , washed with water, a i r dried and r e c r y s t a l l i z e d from 95% ethanol (15 ml.). The y i e l d of pure dialdehyde (51) (orange c r y s t a l l i n e granules) was 1.320 g. (41.6% from (47)). 89 NMR: #6 (CDC13) 6(ppm) #H 1.08 6 1.25 6 1.70-impurity 2.11-impurity 2.45 4 2.69 4 3.94 2 9.41 2 10.82 2 shape t t q q s s bs J(Hz) 7-7.5 7-7.5 7-7.5 7-7.5 MP: 179° (uncorr.) L i t H : 179.5-180.5° (uncorr.) 9C KO H 0 0 (52) 2-Carbethoxy-5-carboxy-3,4-dimethylpyrrole 2-Carbethoxy-3,4,5-trimethylpyrrole (23) (4 0.25 g 0.223 moles) was dissolved i n 300 ml. of methylene chloride i n a 3£ (Erlenmeyer f l a s k . One mole (135 g., 81 ml) of s u l f u r y l chloride was dissolved i n 150 ml. of methylene chloride. To the clear, pale orange pyrrole s o l u t i o n was added 500 ml. of anhydrous d i e t h y l ether a l l at once followed immediately by a l l of the s u l f u r y l chloride solution (over a period of 15-3 0 sec.) causing the solut i o n to turn dark red and a gas t o be evolved. The solu-t i o n was s t i r r e d (magnetic s t i r r e r ) for 1 hr. and then evapo-rated to dryness i n vacuo r e s u l t i n g i n a dark red-brown o i l . The o i l was poured into 500 ml of r e f l u x i n g 80% aqueous acetone and the acetone was allowed to d i s t i l l away. The product c r y s t a l l i z e d a f t e r ^3 0 sec. and the thick s l u r r y was s t i r r e d for 5 min. more then l e f t to s i t on the bench overnight. f i l t e r e d , washed with 80% aqueous acetone and a i r dried. The pale yellowish powder weighed 29.95 g. (a 63.7% y i e l d ) . The following day the carboxylic acid (52) was 91 No nmr analysis was performed due to the product's i n s o l u b i l i t y i n suitable solvents. 92 2-Carbethoxy-5-iodo-3,4-dimethylpyrrole 2-Carbethoxy-5-carboxy-3 ,, 4--dimethylpyrrole (52) (29.95 g., 0.142 moles) was dissolved i n two equivalents of hot aqueous sodium bicarbonate (24.85 g. i n 250 ml. of d i s -t i l l e d water) and f i l t e r e d to remove any insoluble matter. To the hot s t i r r i n g solution was added 150 ml. of 1,2-dichloroethane followed by an aqueous solut i o n (100 ml.) of 1.2 equivalents of iodine (4 3.4 g.) plus an equal weight (43.4 g.) of sodium i o d i d i e . The whole mixture was heated f o r 1 hr. i n a 21 Erlenmeyer f l a s k at r e f l u x temperature (70°, the r e f l u x temperature of the 1,2-dichloroethane/water azeotrope). P r i o r to workup, sodium b i s u l f i t e c r y s t a l s were added to the hot solution to destroy any free iodine (caution: effervescent reaction). On cooling, a product c r y s t a l l i z e d which was f i l t e r e d and washed with d i s t i l l e d water then dissolved wet i n methylene chloride. The aqueous phase was removed (sep-aratory funnel) and the organic phase was f i l t e r e d , heated to r e f l u x and displaced with methanol. When the solu t i o n was thick with c r y s t a l s i t was allowed to cool (to complete the c r y s t a l l i z a t i o n ) , f i l t e r e d , the crystals were washed with methanol and 93 dried. For subsequent crops the mother l i q u o r s and washings were reduced i n volume by d i s t i l l a t i o n and the product (53) allowed to c r y s t a l l i z e . The t o t a l y i e l d of pure white c r y s t a l l i n e iodopyrrole (53) was 27.37 g. (65.8%). M.P. 134-135° (uncorr.) L i t 4 0 ; 134-136° 34 5,5' -Dicarbethoxy-3 , 3 ' , 4 , 4 ' -tetramethyl-2 , 2 ' -bipyrrole 2-Carbethoxy-5-iodo-3,4-dimethylpyrrole (53) (10.0 g., 0.0348 moles) was dissolved i n N,N-dimethyIformamide (50 ml.) i n a 125 ml. Erlenmeyer f l a s k f i t t e d with a drying tube and to the solution was added 10.0 g. of copper bronze. The reaction mixture was s t i r r e d at 100°C (bo i l i n g water bath) for 3 hr. followed by cooling, f i l t r a t i o n of the copper bronze and washing i t with four 50 ml. portions of hot methylene chloride. The combined f i l t r a t e s and washings were extracted i n a separatory funnel with two 100 ml. por-tions of IN hydrochloric acid followed by two 100 ml. por-tions of d i s t i l l e d water. The organic phase was dried and evap-orated to dryness i n vacuo. Any r e s i d u a l DMF was removed on a Rotovap equipped with-a vacuum pump. The crude product was t r i t u r a t e d with low-boiling (30-60°) petroleum ether, f i l t e r e d and washed with more petroleum ether to y i e l d a tan powder (1.203 g, 21.2 %, MP:' 184.5-186°). R e c r y s t a l l i z a t i o n of a sample of the bipyrrole (54) from ethanol afforded a 4 0 product with a melting point of 187.5-188° ( l i t . 194.5-196°) however a second r e c r y s t a l l i z a t i o n from ethanol resulted i n no increase i n the melting point. 94a NMR: #7 (CDC1 3) 6 (ppm) #H shape J(Hz) 1.26 6 t 7-7.5 1.93 6 s 2.23 6 s 4.15 4 q 7-7.5 8.79 2 bs 95 0 (55) 0 5,5 1-Dicarbobenzyloxy-3,3',4,4'-tetramethyl-2,2'-bipyrrole 5,5•-Dicarbethoxy-3,3',4,4'-tetramethyl-2,2'-bipy r r o l e (54) (0.8426 g., 0.00254 moles) was dissolved i n fr e s h l y d i s t i l l e d benzyl alcohol (10 ml.) and heated to b o i l i n g (209°, to drive o f f any remaining water) i n a 50 ml. Erlenmeyer f a l s k (standard taper 14/23) equipped with a r e f l u x condenser, s t i r r i n g bar and nitrogen i n l e t . To the r e f l u x i n g solution was added, a few drops at a time, sodium benzyl-oxide c a t a l y s t (prepared by reacting 4 g. of sodium metal with 50 ml. r e d i s t i l l e d benzyl a l c o h o l ) . The addition of the c a t a l y s t caused a vigorous reaction culminating i n the emission of ethanol vapours and a substantial temperature drop. Catalyst was added u n t i l i t produced no v i s i b l e reaction and the b o i l i n g point of benzyl alcohol was regained. This was followed by immediate quenching of the hot reaction mixture by pouring i t into a solution of 50% aqueous methanol (50 ml.) mixed with g l a c i a l acetic acid (1 ml.) the addition of the ca t a l y s t and was dark green (and contained a grey precipitate) a f t e r the quenching. After cooling i n a n ic e bath, the crude product p r e c i p i t a t e was f i l t e r e d , washed The reaction mixture was dark orange-brown p r i o r to 96 with 50% aqueous methanol (85 ml.) and d i s t i l l e d water (50 ml.) and a i r dried overnight. Th:2 weight of the criide product was 0.9504 g. representing an 82.1% y i e l d . R e c r y s t a l l i z a t i o n of the en t i r e y i e l d from methylene chloride/hexane by displacement resulted i n 0.8066 g. (84.9% recovery) of pale orange-pink, shiny, t i n y c r y s t a l s . NMR: #8 6 (ppm) 1.99 2.29 5.21 7. 27 8.77 #H 6 6 4 10 2 shape J(Hz) MP: 209-210° (uncorr.) Lit40 . 211-212° (uncorr.) s s s s s 97 K 0 H 0 (58) 5,5'-diformyl-3,3',4,4*-tetramethyl-2,2'-bipyrrole 5,5*-Dicarbobenzyloxy-3,3',4,4'-tetramethyl-2,2'-bipyrrole (55) (0.6135 g., 0.0013 moles) was dissolved i n tetrahydrofuran (100 ml.) along with 10% Pd/C c a t a l y s t and was s t i r r e d under a hydrogen atmosphere overnight (uptake = 60 ml., t h e o r e t i c a l uptake = 60 ml.). The THF solution was f i l t e r e d and the ca t a l y s t was washed with more THF. The f i l t r a t i o n and washings were combined and evaporated to dryness. added t r i f l u o r o a c e t i c acid (50 ml., a large excess). The material, i n i t i a l l y a pale green, turned dark green and a white insoluble matter was noticed. The reaction was moni-tored by t i c and to i s o l a t e the di - a - f r e e b i p y r r o l e (57) the t r i f l u o r o a c e t i c acid was evaporated i n vacuo (Rotovap equipped, with vacuum pump). was dissolved i n 14 ml of dry N,N-dimethylformamide under a nitrogen atmosphere (in a 50 ml Erlenmeyer f l a s k equipped with a nitrogen i n l e t and o u t l e t and magnetic s t i r r e r ) and cooled i n 0°C i n an ice bath. Phosphorous oxychloride (0.5 ml., To the f l a s k containing the d i a c i d (56) s o l i d s was The di-a-free residue (57) ( s t i l l wet with TFA) 98 excess, 3.5 equivalents = 0.005 moles = 0.48 ml.) was added to the cold DMF solution which was then s t i r r e d at 0° for 1 hr., at room temperature for 3 0 min. and i n a warm (60°) water bath for 30 min. ( a l l under nitrogen). The reaction mixture was poured into a. s o l u t i o n of 2 00 ml. of d i s t i l l e d water containing 35 g. of sodium acetate. The r e s u l t i n g yellow solution was heated on a steam bath f o r 30 min. (with occasional s t i r r i n g ) causing a yellow p r e c i p i t a t e to form. F i l t r a t i o n , washing with d i s t i l l e d water and a i r drying afforded 0.3393 g. (100%) of ( s t i l l wet) yellow powdery product (58). I t was l a t e r dried under vacuum (0.01 mm., 12 hr., 66°) to remove re s i d u a l water. NMR: #9 (DMSO-D,) <5(ppm) #H shape J(Hz) 1.91 2.24 2.45 3.29 9.54 11.52 6 6 s s m-DMSO residue s-H20 i n DMSO-D 1 1 bs s 99 r (63) Meso-pyrrolyl porphyrin Tripyrrane dialdehyde (34) (8.5 mg, .02 mmoles) was dissolved i n 65 ml. of r e d i s t i l l e d methylene chloride i n a foil-wrapped 125 ml. Erlenmeyer f l a s k equipped with a mag-netic s t i r r e r . To the s t i r r e d solution was added the d i -pyrrane d i a c i d (48) (3.5 ml. stock s o l u t i o n , 0.04 mmole) followed by 1 ml. of HCl-saturated methylene chloride. The mixture was monitored by u.v.-vis. spectra throughout the course of the reaction. After 24 hours the reaction was worked up. The methylene chloride solution was extracted with two equivalents of d i s t i l l e d water to remove the acid, dried by passage through Whatman Phase Separating paper and evaporated to dryness. The residue was dissolved i n 3 ml. of r e d i s t i l l e d 1,4-dioxane and placed i n a 10 ml. round bottomed (T 14/20) fl a s k equipped with a re f l u x condenser DDQ (0.0504 g, 3 equivalents = 0.0428 g) was dissolved i n 2 ml. of dioxane and added to the round bottom f l a s k . The 100 dioxane solution was refluxed for 1 hr.then cooled and f i l -tered to remove the product hydroquinone and other insoluble material. The f i l t e r e d dioxane solution was evaporated to dryness i n vacuo and the residue was redissolved i n a minimum volume of methylene chloride and chromatographed on a pre-parative plate with methylene chloride/methanol (10:1). The second band on the plate (rf ~. 75) was scraped o f f and the compound was eluted from the s i l i c a g el with methylene chloride/methanol (1:1) r e s u l t i n g i n a dark red-brown solu t i o n . To p u r i f y the compound further the solut i o n was evaporated to dryness, and rechromatographed on a t i c plate using the same solvent as before. The major spot (rf .7) on the plate was again scraped o f f and eluted with methylene c h l o r i d e / methanol (1:1) and resulted i n i s o l a t i o n of the meso-p y r r o l y l porphyrin (63). i r #1 see Section 6.3 mass spectrum #1 j 101 Monocarbethoxy nonamethy1sapphyrin Tripyrrane d i a c i d (31) (1 ml. of stock solution; 4.05 mg., .01 mmole) was dissolved i n 25 ml of 95% ethanol i n a 125 ml. Erlenmeyer f l a s k equipped with a magnetic s t i r r e r . To the s t i r r e d s o l u t i o n was added f i r s t the bipyrrole dialdehyde (58) (2.44 mg., 0.01 mmole) followed by 5 ml. of a methanol solu t i o n of p_-toluene s u l f o n i c acid (0.05 M). On addition of the acid the sol u t i o n turned yellow, then orange then dark red, over 30 seconds. An a i r stream was bubbled through the mixture. A f t e r 30 min. the s t i r r i n g solution was dark green and was l e f t to s t i r over-night. The next day the reaction mixture was worked up. To the thanol solution was added one equivalent of methylene chloride and the mixture was then extracted with two equivalents of d i s t i l l e d water. The organic phase was dried and evaporated to dryness and the residue was dissolved i n 3 ml. of methylene chloride and deposited i n a preparative 102 p l a t e . The p l a t e was e l u t e d w i t h methylene c h l o r i d e / methanol (10:1) and the r e s u l t i n g dark green band at r f 0.4 was scraped from the p l a t e . E l u t i o n of the s i l i c a g e l w i t h methylene chloride/methanoi (1:1) r e s u l t e d i n the i s o l a t i o n of the pure sapphyrin (16). 103 (18) M*UOj + Attempted synthesis of the Superbenzporphyrin (18) (A) Isoindole a c e t i c acid (69) (1.91 g. , 0.01 -3 moles) and uranyl chloride (1.36 g., 4 x 10 moles) were placed i n a thick walled tube i n an i n e r t , dry atmosphere and the tube was sealed with a rubber septum. A needle attached to a vacuum l i n e was inserted through the septum on the tube and the tube was evacuated. While under vacuum the tube was sealed with a flame and a f t e r annealing and cooling, the sealed tube was placed i n an oven and heated at 400° for 16 hr. After cooling the tube was opened and the black material within was removed and extracted with pyridine i n a soxhlet extractor. No evidence of superbenzporphyrin formation was observed. (B) Isoindole a c e t i c acid (69) (1.91 g., 0.01 -3 moles), uranyl chloride (1.36 g., 4 x 10 moles) and a-chloronapthalene (5 ml.) were placed i n a t h i c k walled tube under an i n e r t , dry atmosphere and sealed with a rubber septum. As i n (A) the tube was evacuated but t h i s time the 104 solvent was degassed by three freeze, pump and thaw cycles before the tube was sealed. Heating of the sealed tube i n an oven at 400° resulted i n an explosion. Extraction of the glass fragments (to which some organic matter had adhered) with pyridine i n a soxhlet extractor again produced no evidence of formation of superbenzporphyrin (18). 105 5. REFERENCES 1. A.W. Johnson and R. Price, J . Chem. Soc., 1649 (1960). 2. R.B. Woodward and V. Bauer, unpublished r e s u l t s . 3. (a) A.W. Johnson and I.T. Kay, Proc. Chem. S o c , 168 (1961). (b) A.W. Johnson, I.T. Kay and R. Rodrigo, J. Chem. S o c , 2336 (1963). 4. A.W. Johnson and I.T. Kay, J . Chem. S o c , 1620 (1965). 5. R.B. Woodward and R. Hoffmann, "The Conservation of O r b i t a l Symmetry", Academic Press, 1971. 6. F.L. Harris, Research Report, 1968, 7. S-W. Wang, Research Report, 1971. 8. M.J. Broadhurst, R. Grigg and A.W. Johnson, Chem. Commun., 23 (1969). 9. M.J. Broadhurst, R. Grigg and A.W. Johnson, J.C.S. Perkin I, 2111 (1972) . 10. M.M. King, Ph.D. Thesis, Harvard, 1970. 11. J.B. Paine I I I , Ph.D. Thesis, Harvard, 1973. 12. E. Huckel, Z. Physik. , 7_0, 204 (1931); Z. Electrochem., 43, 752 (1937). 13. G.M. Badger, "Aromatic Character and Aromaticity", Cambridge University Press, New York, N.Y., 1969, p. 37. 14. F. Sondheimer, I.C. Calder, J.A. E l i x , Y. Gaoni, P.J. Garratt, K. Grohmann, G. DiMaio, J . Mayer, M.V. Sargent and R. Wolovsky, Special P u b l i c a t i o n No. 21, The Chemical Society, London, 1967, p. 75. 106 15. L.E. Webb and E.B. F l e i s c h e r , J . Chem. Phys., 43_, 3100 (1965); L.E. Webb and E.B. F l e i s c h e r , J . Am. Chem. S o c , 87, 667 (1965) . 16. E.B. Fl e i s c h e r , Accts. Chem. Res., 3_, 105 (1970). 17. W.T. Simpson, J . Chem. Phys., ±T_, 1218 (1949). 18. M. Gouterman, J . Chem. Phys., 3_0, 1138 (1959). 19. M. Kuhn, Helv. Chim. Acta, 42,, 363 (1959). 20. J.E. Falk and D.D. Pe r r i n i n "Haematin Enzymes", J.E. Falk, R. Lemberg, and R.K. Morton, Eds., Pergamon, London, 1961, p.. 56. 21. A. Kowalsky and M. Cohn, Ann. Rev. Biochem. , 3_3, 499 (1964). 22. R.J. Abraham, A.H. Jackson and G.W. Kenner, J. Chem. S o c , 3468 (1961). 23. H.C. Longuet-Higgins and L. Salem, P r o c Roy. S o c , Ser. A., 251, 172 (1959). 24. H.C. Longuet-Higgins and L. Salem, P r o c Roy. S o c , Ser. A, 257, 445 (1960) . 25. C A . Coulson and W.T. Dixon, Tetrahedron, 17, 215 (1962). 26. M.J.S. Dewar and G.J. Gleicher, J . Am. Chem. S o c , 87, 685 (1965). 27. F. Sondheimer, P r o c Roy. S o c , Ser. A, 297, 173 (1967) and references c i t e d therein. 28. J.E. 'Bloor, J. Schlabitz, C C . Walden and A. Demerdache, Can. J . Chem., 42, 2201 (1964). 107 29. V.W. Day, T.J. Marks and W.A. Wachter, J . Am. Chem. Soc. , 9J7, 4519 (1975) . 30. G.P. Arsenault, E. Bullock and S.F. MacDonald, J. Amer. Chem. S o c , 8_2, 4389 (1960). 31. (a) R.B. Woodward, Angew. Chem., 72, 651 (1960); (b) J.B. Paine I R.B. Woodward.. and D. Dolphin, J. Org. Chem., 4_1, 2835 (1976). 32. (a) A.W. Johnson, E. Markham, R. Pr i c e and K.B. Shaw, J. Chem. S o c , 4254 (1958). (b) G.C. Kleinspehn and A.H. Corwin, J . Org. Chem., 25, 1040 (I960). (c) G.C. Kleinspehn, J . Amer. Chem. S o c , 77^ , 1546 (1955). (d) H. Fischer and E. Fink, Z. Physiol. Chem., 280, 123 (1944). (e) L. Knorr, Ber. , 1_7, 1635 (1884); Ann. 236, 290 (1886). (f) L. Knorr and H. Lange, Ber., 35, 2998 (1902). 33. (a) A.H. Corwin, W.A. Bailey, J r . , and P. V i o h l , J . Amer. Chem. S o c , 6£, 1267 (1942). (b) A.H. Corwin and J.L. Straughn, i b i d , 70, 1416 (1948). (c) • G.C. Kleinspehn and A.W. Corwin, i b i d , 7_5, 5295 (1953). 34. K.W. Doak and A.H. Corwin, J . Amer. Chem. S o c , 71, 159 (1949). 35. J . E l l i s , A.H. Jackson, A.C. Jain and G.W. Kenner, J . Chem. Soc. 1935 (1964). 1.08 36. H.W. Whitlock and R. Hanauer, J . Org. Chem., 3_3, 2169 (1968). 37. G.C, Kleinsphn, J. Amer. Chem. S o c , 1546 (1955). 38. R. Chong, P.S. Clezy, A.J. Liepa and A.W. Nichol, Au s t r a l . J . Chem., 2_2, 229 (1969). 39. A.W. Johnson, I.T. Kay, E. Markham, R. Price and K.B. Shaw, J . Chem. S o c , 3416 (1959). 40. R. Grigg, A.W. Johnson and J.W.F. Wasley, J . Chem. S o c , 359 (1963). 41. G.C. Kleihspehn and A.E. Briad, J. Org. Chem., 2§_, 1652 (1961). 42. Acid concentration of methylene chloride reaction mixtures was measured by extraction of the HC1, from an equivalent amount of c a t a l y s t , into a known volume, of d i s t i l l e d water and 'measuring the acid concentration i n the aqueous solution. 43. With assistance from R.E. Carlson i n the use of the Waters High Pressure Liquid Chromatography packing: Sephadex LH-20. 44. J.E. Falk, Porphyrins and Metalloporphyrins, E l s e v i e r , 1964, p. 84. 45. A.H. Jackson, G.W. Kenner and K.M. Smith; and R.T. Apli n , H. Budzikiewicz and C. Dj e r a s s i , Tetrahedron, 2_1, 2913 (1965). 109 46. M. Broadhurst, R. Grigg and A.W. Johnson, J . Chem. S o c , Perkin I, 2111 (1972) . 47. J.W.A. Findlay and A.B. Turner, Organic Syntheses, C o l l . Vol. V, H.E. Baumgarten, Ed. r Wiley (1973), p. 428. 48. R.B. Woodward, Ind. Chem. Belg., 1293 (1962). 49. P.S. Clezy, A.J. Liepa and N.W. Webb, Aust. J. Chem., 2_5, 1991 (1972). 50. R. Grigg i n The Porphyrins, D. Dolphin, Ed., Academic Press, i n press. 51. CO. Bender, R. Bonnett and R.G. Smith, J. Chem. S o c , 1251 (1970). 52. Prepared by Dr. T.B. Tsi n , University of B r i t i s h Columbia. 53. Prepared by eithe r J.B. Paine III (see Kef. 11), or J.G. Shelling (summer student, 1975). • 54. J.J. Katz i n The Porphyrins, D. Dolphin, Ed., Academic Press, i n press. 110 6. SPECTRA PAGE 6.1 Nuclear Magnetic Resonance . . I l l 6.2 V i s i b l e E l e c t r o n i c Absorption 114 6.3 Infrared Spectrum and Mass Spectrum for the meso-pyrrolyl porphyrin (63) 118 nmr #10 I l l 112 i • I i • i i ' I i i i i ' | i i i i i I i i I j i o 1 4001 I 500 I f I I M I i > rrr „ •if (•ui ^iL 1 I 1 1 , 1 I .. 1 • 1 I i 1 t 1 1 I 1 I 1 1 i I 1 1 •H J _ L 4 - 1 • • • I I 1 I—I r 1 I I I I I I 1 I I 1 I I 1 I I I I 1 I 1 , 1 I . l i i i I I ! uJ—I—1—I—1—I—I T rTTa 4.0 _ 30 . *3.o K O _ _ 0 ' I 1 I 1 1 I 1 500 > no 10 . 1 • 1 1 1 1 11 1 )—r 1 1 1 1 ~ | — 1 — r n — \ 1 1—1 1 1 I ~T ' 'MO' 1 I 1 1 ' ' 1 l . i I I 1 r 1 r r lea 1 0 «. >'r. ( T * L/—4-I I I I • 1 I 1 1 I • t I 1 • I • i- I 1 1 I 1 1 I 1 1 1 1 t I 1 1 1 1 1 I I 1 i 1 1 1 I 1 .• 1 I 1 1 1 1 1 I 1 1 1 i, I 1 1 1 1 I ii. t 1 - 1 I 1 1 1 1 . 1 1 1 1 1 UJ—1_J_ t . O ' 5 i o £ 5 S J 3 "-^ . 40 R ~ ~ ~ i —1—1— 1 — i —1— r r - ] —T—1—1— f —I—1—1— 1 — 1—I— 1—r 1—r I I I ! I 1  I I T 7 : •  I '• I t . I . I I 1 1 I 1 I I I 1 I • 1 ) 1 1 j I I I I i j 1 I I I I j •! 113 ~T—1 I 1 I I I I I I I I I > • » * I ' I ' ' t • « ' * I ' ' L " | i i 1 i | 1 ' i | 11 1 If 4091 I M O r I • • I . i I i T I i i i i = • \ I M l 'l | I I I T T + T tool 0 ~ 7 — i • I .• • I I • I I I M I | ! I I I I I I i i i T T T i i . l i ' I I I . I • I I I I I I I 1-1 J L - L L . I I I I I l I I 114 200 115 SPECTRUM #2 Change i n v i s i b l e spectrum of 3 + 2 reaction mixture with time. ^ SPECTRUM #4 Sapphyrin reaction, crude reaction mixture —. Pure sapphyrin (16) *0.1 cm. path length c e l l , ( a l l others, 1 cm. path length c e l l . ) 

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:
https://iiif.library.ubc.ca/presentation/dsp.831.1-0061055/manifest

Comment

Related Items