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The action of carbon monoxide and dicobalt octacarbonyl on some aromatic oximes O'Donnell, Joseph Patrick 1959

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THE ACTION OP CARBON MONOXIDE AND DICOBALT OCTACARBONTL ON SOME AROMATIC OXIMES by Joseph P a t r i c k O'Donnell & THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE i n the Department of Chemistry We accept t h i s t h e s i s as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA July, 1959 ( i i ) Abstract When syn-benzaldoxime was reacted with carbon monoxide containing about 0.04 volume percent of hydrogen and d i c o b a l t octacar- bonyl i n benzene sol u t i o n at elevated temperatures and pressures the following compounds were produced; sym-dibenzylurea (35/0, mono- benzylurea (10$) and benzaldehyde (10$). Also i s o l a t e d were 15$ y i e l d s of two u n i d e n t i f i e d components r e f e r r e d to as compounds A and B. When benzophenone oxime was subjected to the same r e a c t i o n conditions the major product was 3-phenylphthalimidine (75$). Also i s o l a t e d was a 5% y i e l d o f an u n i d e n t i f i e d component c a l l e d compound B. I t was demonstrated that under the re a c t i o n conditions used con siderable amounts of d i c o b a l t octacarbonyl are needed f o r successful r e a c t i o n . When the octacarbonyl was present i n only c a t a l y t i c amounts the course of the observed r e a c t i o n was g r e a t l y affected and the major i s o l a t e d product was benzophenone (70$). Small amounts of 3-phenylphthalimidine and of the o r i g i n a l oxime were also i s o l a t e d . When the 0-methyl ether of benzophenone oxime was reacted the only product i s o l a t e d was 3-phenylphthalimidine i n 75$ y i e l d . Reaction pressures corrected to constant temperature are plot t e d against reaction time f o r each substrate and the r e s u l t s discussed. ( i i i ) A new method of synthesizing the O-methyl ether of benzo phenone oxime (using O-methyl hydroxylamine), and a dichromate-acetic a c i d oxidation of sym-dibenzylurea g i v i n g a high y i e l d of dibenzoylurea are described. A platinum oxide i n a c e t i c a c i d reduction of 3-phenylphthalimidine which reduced both benzene r i n g s but l e f t the lactam group i n t a c t i s also described. Infrared spectra are included f o r a l l compounds obtained. In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f the requirements f o r an advanced degree at the U n i v e r s i t y o f B r i t i s h Columbia, I agree t h a t the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and study. I f u r t h e r agree t h a t permission f o r e x t e n s i v e copying of t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the Head of my Department or by h i s r e p r e s e n t a t i v e s . I t i s understood t h a t copying or p u b l i c a t i o n of t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l not be allowed without my w r i t t e n p e r m i s s i o n . Department of Chemistry  The U n i v e r s i t y of B r i t i s h Columbia, Vancouver 6*, Canada. Date J u l y 20, 1959  Acknowledgement The writer wishes to express his thanks to Dr. A. Rosenthal for his patience, advice and encouragement i n the direction of this research project. The writer also wishes to thank Dr. J e Halpern for helpful discussion of reaction pressure plots. Table of Contents Page T i t l e Page ( i ) Abstract ( i i ) Acknowledgement ( i v ) Table of Contents (v) L i s t of Figures ( v i i i ) I. . H i s t o r i c a l Introduction 1 A. Reactions of oximes 1 B. Isomerism of oximes 1 C. Reactions of carbon monoxide 2 D. Di c o b a l t octacarbonyl and r e l a t e d compounds 6 E. Hydroformylation - the oxo reaction 11 F. Carbonylation 14- G. Reactions r e l a t e d to hydroformylation 16 H. Reactions i n v o l v i n g carbon monoxide. with nitrogen compounds 17 I. Reactions of carbon monoxide i n v o l v i n g r i n g formation 20 I I . Discussion 25 Reactions of carbon monoxide and d i c o b a l t octacarbonyl with A. Syn-benzaldoxime 25 B. Benzophenone oxime 30 ( v i ) Page C, 0-methyl ether of benzophenone oxime 3 4 D. Discussion of pressure p l o t s 35 I I I . Experimental 39 A. General 3 9 B. Reaction of syn-benzaldoxime with carbon monoxide i n the presence of d i c o b a l t octacarbonyl AO a. Preparation of reactants 4 0 b. Reaction procedure 40 c. Separation and i d e n t i f i c a t i o n of products 43 d. Repeat of rea c t i o n between carbon monoxide and syn-benzaldoxime i n the presence of d i c o b a l t octacarbonyl 54 C. Action of carbon monoxide on benzophenone oxime i n the presence of d i c o b a l t octacarbonyl 59 a. Preparation of benzophenone oxime 59 b. Reaction procedure 59 c. Separation and i d e n t i f i c a t i o n of products 60 d. Repeat of rea c t i o n of benzophenone oxime 65 e. Reaction of benzophenone oxime i n the presence of a small amount of d i c o b a l t octacarbonyl 69 D. Reaction of 0-methyl ether of benzophenone oxime i n the presence of d i c o b a l t octacarbonyl 71 a. Preparation of 0-methyl ether of benzophenone oxime 71 ( v i i ) b. Reaction procedure 71 c. Separation and i d e n t i f i c a t i o n of products 72 IV. Bibliography 76 L i s t of Figures 1. P l o t of pressure against time f o r the r e a c t i o n of syn-benzaldoxime v i t h carbon monoxide i n the presence of d i c o b a l t octacarbonyl 2. Chromatography of syn-benzaldoxime r e a c t i o n products 3. Infrared spectrum of compound A 4. Infrared spectrum of compound B 5. In f r a r e d spectrum of sym-dibenzylurea compared with that of sym-dibenzoylurea 6. Infrared spectrum of mono-benzylurea 7. Infrared spectrum of 3-phenylphthalimidine compared with that of i t s reduced product 8. P l o t of pressure against time f o r the rea c t i o n of benzophenone oxime with carbon monoxide i n the presence of d i c o b a l t octacarbonyl 9. P l o t of pressure against time f o r the reaction of the O-methyl ether of benzophenone oxime with carbon monoxide i n the presence of d i c o b a l t octacarbonyl ( v i i i ) Page 42 44 46 47 49 55 64 66 73 1 HISTORICAL INTRODUCTION A. Reactions of Oximes. The Beckmann rearrangement has been investigated by many workers. Its generality and mechanism are now well established (23), (47), Catalysts for this reaction include concentrated sulphuric acid, phosphorous pentachloride, polyphosphoric acid (35)» (27), hydrogen chloride, boron trifluoride and benzenesulphonyl chloride. Hydrolysis of an oxime w i l l regenerate the parent carbonyl compound. Oximes are generally amphoteric and form well characterised salts of both types* They are reduced by many agents to amines* Aldoximes may be dehydrated to produce n i t r i l e s ; oximes w i l l form esters with common esterifying agents. This i s believed to be the necessary f i r s t step i n the Beckmann rearrangement (47). B. Isomerism of Oximes Three distinct types of isomerism are possible for oximes* F i r s t i s the geometrical syn and anti type where the hydroxyl can be cis or trans to an identifiable radical attached to carbon. These isomers have been isolated i n the aromatic series but similar isolation of pure compounds has not yet been achieved with aliphatic analogs (26), Second i s the oxime-nitroso tautomeric equilibrium. T i l l recently i t 2 has been believed that this equilibrium was almost 100$ in favor of the oxime form, for primary and secondary oximes (56). However recent work has shown that large scale preparation of many primary and secondary nitroso compounds is possible (12), (7). The opinion has been expressed (16) that hydroxylic solvents and low concentrations favor formation of the oxime. Third i s the oxime-nitrone equilibrium. Recent information (9) indicates that oximes may normally exist in equilibrium with a small percentage of the nitrone form. Semper and Liehenstadt (45) isolated four different methyl ethers when they treated benzaldoxime with methyl sulphate. 0- and N- ethers were formed in approximately equal amounts, C. Reactions of Carbon Monoxide by Orchin and Wender (33). These authors show carbon monoxide can react as a Lewis base, a Lewis acid, or as a free radical. As a base i t can react with carbonium ions according to the following scheme The reactions of carbon monoxide have been reviewed recently + + 3 This carbonium ion can now react with nucleophilic reagents present in the system to form esters, acids or anhydrides. Anhydride formation i s shown here RCKjCO + R COOH OHO II i it R-CHg-^ O-G-R 0 0 Hi HI RCEJC-O-C-R" + H + These reactions allow the formation of esters, acids, or anhydrides from olefins, alcohols, ethers and to a limited extent from ketones or aldehydes provided the conditions for formation of the ap propriate carbonium ion are present in the system. Carbon monoxide also acts as an electron acceptor though examples of this are less extensive. The synthesis of sodium formate is an established example 6'::bV + OH" H0:C:0r Acid formation from alcohols i s known in the presence of alkoxide ion C2H50H + CO HC00C2H5 4 Carbon monoxide reacts vith Grignard reagents; for example the reaction with tert-butyl magnesium chloride i s shown 0 ni 2(CH3)3-G-MgCl + 2C0 ^ (C^^fc-CHOB-CCCHj) There are isolated examples i n vhich carbon monoxide reacts by a radical mechanism especially when photosensitized* Its reaction with ammonia to produce formamide i s believed to proceed by such a mechanism, MH3 + CO > HCONRj However radicals with a carbonyl group more commonly decom pose according to the following scheme RCH^ CO ^ RCH- + CO A radical i n i t i a t e d copolymer!zation of carbon monoxide and ethylene has recently been reported. Foster et a l (14) report formation of such a polymer including such chain transfer agents as ethyl mercaptan, carbon tetrachloride, and alcohols. An unusual reaction discovered by Buckley and Ray (6) i l l u s  trates the reducing action of carbon monoxide. When aniline containing a small amount of aniline hydrochloride reacted at 250° C under 3000 5 atmospheres pressure carbon dioxide and a brown amorphous solid were obtained. This was shown to be a cross linked polymer of I. I I t was believed this intermediate was obtained by reduction of II ^ C H ^ ^> NH2 OH II which i n turn had been formed by condensation and rearrangement of two moles of formanilide. The same authors found manyjorganic compounds were reduced by carbon monoxide at high temperatures and pressures with the formation of carbon dioxide. Without catalyst nltro, nitroso and azoxybenzenes were reduced to azobenzene and phenylhydroxeylamine was reduced to aniline. In the presence of Raney cobalt benzyl alcohol, phenylmethylcarbinol and benzhydrol were reduced to the corresponding hydrocarbons. Buckley and Ray also discovered a remarkable stepwise reduction to produce III 6 N - N n tii HC. /CH N NE, I I I from carbon monoxide and hydrazine under extreme conditions. D. D i c o b a l t octacarbonyl and r e l a t e d compounds. I. Formation and properties ( r e f 53, pp 89 to 106) The formation of d i c o b a l t octacarbonyl from a cobalt s a l t may be written i n the f o l l o w i n g manner Hg 5? 2H + + 2e 2H + + 2e + 00(0^)2 5* Co + 2H0AQ 2Co + SCO ^ Co 2(C0)g This r e a c t i o n i s c a r r i e d out at 160° C using a s l u r r y of a c o b a l t s a l t with benzene under 3200 p . s . i . of a 111 mixture of carbon monoxide and hydrogen. This r e a c t i o n a c t u a l l y forms cobalt hydrocarbonyl (H Co(CO)^) as has been proven by c o o l i n g the r e a c t i o n vessel to -51° C before r e l e a s i n g the gas pressure. D i c o b a l t octacarbonyl i s formed only on 7 r e l e a s i n g the pressure at room temperatures. Under a s l i g h t pressure of carbon monoxide the octacarbonyl i s stable i n d e f i n i t e l y at room temperatures. In the absence of carbon monoxide decomposition takes place according to the f o l l o w i n g equation 2 C o 2 ( C 0 ) 8 > C % ( C 0 ) 1 2 + 4 0 0 The octacarbonyl i s r e a d i l y soluble i n hydrocarbon solvents but reacts more or l e s s r e a d i l y with polar solvents such as alcohols, ketones, amides and amines. The tetramer, ( C o ^ G O ) ^ ) * i s pyrophoric but i n d e f i n i t e l y stable i n an i n e r t solvent. Cobalt hydrocarbonyl (HCo(CO) ), forms pale yellow c r y s t a l s 4 stable below t h e i r melting point (-26° C). Above t h i s temperature i t decomposes r a p i d l y . 2 HCo(CO)^ + Co 2(C0)g I t i s a stable strong a c i d i n oxygen f r e e aqueous s o l u t i o n at 25° G and may be t i t r a t e d using phenolphthalein as an i n d i c a t o r . The accepted e l e c t r o n i c structures f o r these compounds are shown below: ( I I I , IV) 8 0 It; cv c c \ / \ / 0=C —Co C o - C~-0 / \ / \ C C Cx G I I I C C H-Co I V c IV II.. Reactions The reactions of d i c o b a l t octacarbonyl may be c l a s s i f i e d as follows (a) Homomolecular disproportionation \ 3Cb2(C0)g + xB CbBx 00(00)^ + SCO B may be ammonia, water, methanol, ethanol, p i p e r i d i n e or formamide. The group B must be a Lewis base and f u l f i l l geometric requirements. Where B i s a primary or secondary a l i p h a t i c amine s a l t formation may take place according to the following equation N N , B + Co2(C0)g BCo(CO), 00(00)^ Hieber and Wiesboeck (21) examined the products when many nitrogen bases reacted with d i c o b a l t octacarbonyl. They used p i c o l i n e , quinoline, pyridine, a n i l i n e and others, and a r r i v e d at t h i s general equation where B represents a monofunctional nitrogen base. /Co(C0V 12B CoB, 00(00)^ + SCO Formamide also formed a compound of analogous composition. Oxygen bases formed compounds of d i f f e r e n t composition. Acetophenone f o r example reacted as follows 0 n 3 (Co(CO) Aj + ph-C-CH3 y-f- Co(ph-C-CHo)i- 0 it Co(CO)^ + 8C0 These compounds were generally formed near 5 C and some could be des troyed by r e f l u x i n g s l i g h t l y above room temperature i n l i g h t petroleum ether. (b) External e l e c t r o n t r a n s f e r D icobalt octacarbonyl w i l l r e a c t with m e t a l l i c sodium or hydroxyl i o n according to the fol l o w i n g equations. 10 2 Na + Co 2(C0) 8 ^ 2 NaCo(C0)A 2 Co(C0) 8 + 40H" ^ 4 Co(CO), + 2^0 + 0 2 (c) Replacement of the carbonyl group I s o n i t r i l e s , the RS group of mercaptans, and acetylene have been shown to replace one or more carbonyl groups. Acetylene f o r example replaces the two bridge carbonyl groups according to Co2(C0)g + HG 5.GH 5 ^ C o ^ C O ^ E , + 2C0 S l y (A6) reports a d e t a i l e d X^-ray c r y s t a l l o g r a p h i c study of diphenyl acetylene d i c o b a l t hexacarbonyl and reports i t s structure as shown. He found that each carbon was bonded to each cobalt and that the plane of the carbon-carbon bond was roughly at 90° to the plane of the 11 Cobalt-cobalt bond. S l y stated that t h i s structure represents one o f the f i r s t molecules to be studied which e x h i b i t s a multipoint attachment of a s i n g l e organic molecule to more than one metal atom. He f e e l s t h i s i s p o s s i b l y analogous to the postulated attachment o f an organic substrate to a metal surface during heterogeneous c a t a l y t i c reactions. E. Hydroformylation - The Oxo Reaction I. Nature and scope of the r e a c t i o n The l i t e r a t u r e concerning t h i s r e a c t i o n has been extensively reviewed by Vender e t a l (53). The o v e r a l l r e a c t i o n i s most e a s i l y v i s u a l i z e d as i n v o l v i n g the a d d i t i o n of a hydrogen atom and a formyl group across the double bond of an o l e f i n . Conditions f o r the r e a c t i o n are approximately 75 to 200° C under 100 to 300 atmospheres of a mixture of carbon monoxide and hydrogen i n the presence of a cobalt c a t a l y s t . I t appears that at l e a s t three carbonyls of cobalt are involved i n the addition of carbon monoxide and hydrogen to an o l e f i n . These are d i c o b a l t octacarbonyl, cobalt hydrocarbonyl, and the cobalt t r i c a r b o n y l tetramer. I t i s of i n t e r e s t to note that the hydroformylation of an o l e f i n occurs p r a c t i c a l l y to the complete exclusion of i t s hydrogenation even though the f r e e energy change f o r the hydrogenation i s much greater than that f o r the hydroformylation reaction. Hydrogenation becomes a competitive r e a c t i o n when the o l e f i n i c linkage i s conjugated. Every simple o l e f i n submitted to hydroformylation conditions has been shown to undergo t h i s reaction^ 12 Double bond isomerization occurs r e a d i l y under hydroformy l a t i o n conditions. For example the products obtained when 1-pentene and 2-pentene are submitted to the r e a c t i o n are the same. This i s found i n s p i t e of the observed f a c t that isomerization i s a slow pro cess compared to hydroformylation (55). The amount of hydrogen present has no p a r t i c u l a r e f f e c t on the rate of isomerization. Isomerization occurs i n the absence of hydrogen and i s not f a s t even when large amounts of hydrogen are added (10, 11). These f a c t s l e a d to the as sumption that the structure of the o l e f i n carbonyl complex i s the same f o r both 1 and 2-pentene. Some mechanism must e x i s t f o r the f a c i l e movement of hydrogen i n these complexes. In general the s t r a i g h t chain aldehyde i s the favoured product. I I . Mechanism Wender and Sternberg (55) point out that the Fischer-Tropsch synthesis i s probably a heterogeneously catalyzed r e a c t i o n since i t takes place at comparatively low pressures below the point where the tendency toward formation of metal carbonyls becomes la r g e . The f o r * mation of metal complexes destroy the surface intermediate. In contrast hydroformylation i s homogeneously catalyzed. Homogeneous reactions catalyzed by the carbonyls involve formation of soluble metal complexes. They also observe that i t i s l i k e l y that a l l three reactants, that i s , o l e f i n , carbon monoxide and hydrogen are united i n one complex at some stage of the reaction. The f o l l o w i n g mechanism i s presented i n the 13 l i g h t of t h i s i d e a and appears to agree with a l l a v a i l a b l e data. Cyclohexene i s used i n t h i s example. C 6H 1 £ ) + C o 2 ( C 0 ) 8 C o 2 ( C O ) 7 C 6 H 1 G + CO V may have the structure shown, by analogy with the proven structure of acetylene complexes (4-6). 0 II (CO), R Co C H Co C H (co). The ease of formation of V i s strongly influenced by the s t e r i c requirements of the o l e f i n ( r e f 53, p. 79). C o 2 ( C 0 ) 7 C 6 H 1 0 + H 2 C o 2 ( C 0 ) 6 + C 6H nCH0 This equation i s most probably r e a l i z e d i n two steps. The complex V probably s p l i t s a hydrogen molecule, as shown, to obtain the complex VI. 14 0 n (CO), Co— H H — C o (CO), H — C A R H VI In the next step VI s p l i t s to form d i c o b a l t hexacarbonyl and the product aldehyde. Then d i c o b a l t hexacarbonyl reacts with carbon monoxide to reform d i c o b a l t octacarbonyl. In contrast with the above mechanism Aldridge et a l ( l ) suggest that the hydroformylation r e a c t i o n may be heterogeneously catalyzed. They report data from which i t can be deduced that the r a t e of hydroformylation of an o l e f i n i s not d i r e c t l y dependent upon the amounts of soluble cobalt present under reaction conditions. The i n s o l u b l e cobalt may provide a f r e s h h i g h l y a c t i v e metal surface which i s constantly being consumed and deposited by carbonyl formation and breakdown. These authors conclude that i t appears l i k e l y that any d i r e c t r o l e i n hydroformylation c a t a l y s i s that cobalt carbonyls or cobalt hydrocarbonyls may play must be c a r r i e d out i n conjunction with a solid, c obalt surface. F. Carbonylation R e l a t i v e l y l i t t l e appears i n the l i t e r a t u r e about a system which contains no hydrogen, c o n s i s t i n g of the substrate, carbon monoxide 15 and the metal carbonyl c a t a l y s t . A r e a c t i o n mechanism has been proposed by Tirpak et a l (50) f o r the system where a d i s u b s t i t u t e d acetylene i s allowed to r e a c t with carbon monoxide and d i c o b a l t octacarbonyl i n the absence o f hydrogen. Di s u b s t i t u t e d acetylenes form stable compounds by r e p l a c i n g the bridge carbonyls of d i c o b a l t octacarbonyl (see page 10, r e f . 46). These have the composition RC2R'CO2(C0)^. Tripak quotes Sternberg et a l (48) who have e s t a b l i s h e d that a d i c o b a l t nonacarbonyl can be produced under c e r t a i n conditions. This involves the homolytic f i s s i o n of the cobalt-cobalt bond to add a t h i r d bridge carbonyl to produce the structure VII. 0 n 0 — 0 Co C • Co C = 0 n 0 VII By analogy with t h i s compound he suggests the presence of VIII i n the acetylenic r e a c t i o n . 16 0 tt; (CO), Go C — C o (CO)- \ o / c = c / \ R R V I I I This would be formed i n the f i r s t step of the r e a c t i o n f o l  lowed by decomposition to obtain the more stable structure analogous to that of S l y (46). G. Reactions Related to Hydroformylation Lonsbury and Meschke (25) reacted cyclohexene at 800 atm and 300° C with carbon monoxide and hydrogen. They obtained besides the expected hydroformylation products a perhydrofluorenone 0 They showed t h i s compound could be produced i n the absence of hydrogen or any c a t a l y s t . An analogous product could be obtained from cyclopen- tene but no reaction occurred with a v a r i e t y o f a l i p h a t i c o l e f i n s . The authors o f f e r no suggestions o f a possible mechanism f o r the r e a c t i o n . 17 A 91$ conversion of o l e f i n s to aldehydes has been reported (43) using a cobalt, t h o r i a , magnesia, c a t a l y s t under hydroformylation conditions. The product appeared i n a greenish black s o l u t i o n con t a i n i n g cobalt carbonyls. Nakamura (31) reports reduction of S c h i f f bases under hydro formylation conditions. Reaction of benzalcyclohexylimine f o r 4 hours at 135° C produced 79$ of benzylcyclohexylamine. The authors noted those S c h i f f bases which are most conjugated are most e a s i l y reduced and form the lowest amounts of resinous byproducts. They also noted amines, e s p e c i a l l y a l i p h a t i c s , lower the y i e l d considerably. This i s poss i b l y connected with the type of rea c t i o n mentioned by Hieber (page 9, r e f . 21). K i r c h and Orchin (24) showed that complex formation does take place i n a toluene s o l u t i o n of cobalt hydrocarbonyl and 1-hexene. At 0° C the s o l u t i o n absorbed 2 moles of carbon monoxide. At 25° C the complex decomposed to form aldehydes. The authors state the complex has the composition 2HCo(C0)^RC0 where R represents o l e f i n . Rosenthal and Read (41) reported that when 3, 46, t r i O-acetyl-D-galactal was allowed to react under hydroformylation con d i t i o n s a hydroxymethyl group was added across the double bond. Nuss- baum e t a l (32) re c e n t l y reported a s i m i l a r a d d i t i o n o f a hydroxy methyl group to a double bond of a s t e r o i d nucleus. H. Reactions of carbon monoxide i n v o l v i n g nitrogen compounds. The work of Buckley and Ray (6) and that of Hieber and Wies-18 boeck (21) has already been r e f e r r e d to. H a l l well (19) reported the formation of dimethylglycine from formaldehyde and dimethyl amine according to the equation HGHO + (CH3)2NH j^1 > (CE^HCHgCOGH Tyson and Shaw (51) produced the 3 carboxaldehyde d e r i v a t i v e from potassium indole using a d i c o b a l t octacarbonyl c a t a l y s t . When in d o l i n e was reacted under s i m i l a r conditions the N-formyl compound was i s o l a t e d . The authors concluded that N-formyl indole isomerized r e a d i l y to the 3 d e r i v a t i v e under r e a c t i o n conditions. These authors obtained no conclusive r e s u l t s when 2 or 3 substituted i n d o l e s were used (52). S t e r i c e f f e c t s were believed responsible f o r the f a i l u r e of the reaction. Winteler et a l (57) reacted primary and secondary amines with carbon monoxide at 150 atm i n the presence o f sodium alco h o l ate. The o v e r a l l r e a c t i o n was 0 n R'R"NH > R V N - C H They noted the rate of reaction increased r a p i d l y with temperature. They postulated that the f i r s t step i n the reaction was the addition o f carbon monoxide to the alcoholate RO + CO ^ > R-C = 0 — ^ R-C 19 This then reacted with the amine R-COOH + R2NH ^ F^NCH + ROH Teter and Olson (49) produced n i t r i l e s from o l e f i n s and ammonia using a mixture of CoSO^ and NiSO^ as c a t a l y s t at 340° C and 100 atmospheres; the o v e r a l l r e a c t i o n was CH3-CH = CHg + NH 3 CH 3-CH 2-C=N Using extreme conditions Bengelsdorf (3) produced IX from aromatic n i t r i l e s Ar t C '/ \ N N 3 Ar - C = N =5* I || IX This s - t r i a z i n e trimer was formed at 50,000 atm and 500° G. Benzamide under these conditions was dehydrated i n s i t u and produced an analogous product. Syn-benzaldoxime, a s t r u c t u r a l isomer of benzamide, when subjected to these conditions decomposed e x p l o s i v e l y to produce ammonia and a carbonaceous material resembling amorphous carbon. 20 When O - t o l u n i t r i l e was subjected to r e a c t i o n conditions the analogous product was obtained i n poor y i e l d showing s t e r i c hindrance i s not overcome even at these extreme pressures. Phosphoric a c i d {$5%) however allowed a quantitative y i e l d from O - t o l u n i t r i l e . P h t h a l o n i t r i l e y i e l d e d phthalocyanine. Saner et a l ( 4 4 ) reacted 3 , diethylamino-propyne-1 at 1 2 5 ° C and 5 0 0 atmospheres of carbon monoxide to produce 2 , 3 dihydro, 3 (NN d i e t h y l formamido), 5 d i e t h y l amino furan, i n 4 4 $ y i e l d . They reported E t I N - CH-, - C=E CH E t R \ 0 n N - C / H T T o H — N that c a t a l y t i c amounts of d i c o b a l t octacarbonyl were required f o r t h i s r e a c t i o n . I , Reactions of Carbon Monoxide Involving Ring Formation. P r i t c h a r d (36) c y c l i z e d the aromatic amide N,N-dibenzoyl~ 0 n 0 it 0 tt a n i l i n e with carbon monoxide at 3 2 5 C using a n i c k e l carbonyl c a t a l y s t . - ph +• <x ^ / ph ^ V ^ C n 0 ph - C - N — C - ph t 21 The products were N-phenylphthalimide and benzene. Benzoic anhydride reacted s i m i l a r l y to produce p h t h a l i c anhydride and benzene. B e n z o n i t r i l e and benzoic acid apparently reacted above 250° C to give dibenzamide, which subsequently c y c l i z e d to give phthalimide. I t i s noted here that no carbon monoxide i s used. I t s f u n c t i o n i s not known although the reactions f a i l without i t . P r i t c h a r d (37) subsequently prepared N-substituted p h t h a l i  midine s from N-substituted imines as shown. CH = N - ph N - ph 0 He c a r r i e d out the r e a c t i o n with d i f f e r e n t substituents both at the 3 p o s i t i o n and on the r i n g on which the r i n g closure occurred. Pr i t c h a r d also submitted phenyl bromide to the r e a c t i o n conditions adding a l k a l i carbonates. The products were ph t h a l i c an hydride and benzene which apparently were obtained through preliminary formation of benzoic anhydride. Prit c h a r d (38) f u r t h e r reacted azobenzene with c a t a l y t i c amounts of n i c k e l corbonyl at 250° C. The r e a c t i o n absorbed at l e a s t two moles of carbon monoxide. They i s o l a t e d 2 phenyl indazolone (X) from the mixture. 22 H N C N - ph X Murahashi and H o r i i e (30) also reported on azobenzene. They shoved that at 190° G the c h i e f product was the indazolone X but they reported that at 230° C a second mole of carbon monoxide was absorbed to produce XI H N /° N - ph XI Substituents i n the A p o s i t i o n (chloro or dimethylamino) d i d not a f f e c t the r e a c t i o n except that r i n g closure occurred on the r i n g c a r r y i n g the substituent. Diphenylurea was obtained i n small amounts as a byproduct. 23 Murahashi (29) reported that the r e a c t i o n with benzaldehyde a n i l f a i l e d with n i c k e l c a t a l y s t s but r i n g closure occurred i n 80% y i e l d with d i c o b a l t octacarbonyl present. N - p h 200 atm 230° C 6 hours C H 2 C II N-ph 1-Naphaldehyde a n i l produced an analogous compound. I t i s worthy of note that r i n g closure occurred to produce the l i n e a r isomer, whereas 2 substituted napthalenes u s u a l l y substitute f u r t h e r i n the 1 p o s i t i o n . Rosenthal et a l (40) have reported examples of r i n g closure using aromatic oximes to produce substituted phthalimidines., This r e a c t i o n has been successful f o r benzophenone oxime and acetophenone oxime. Benzyl phenyl ketoxime gave both possible products. C y c l i z a t i o n took place to each a v a i l a b l e r i n g to produce 3 benzylphthalimidine and 3-phenyl, 3-4-dihydroisocarbostyril. 2A C H 2 / V S - OH 00(150 atm) C o 2 ( C 0 ) 8 230° C H / CH. / ph t V 7 \ \ / C it NH I t i s notable that the expected product would be the N-hydroxy compound. Apparently the known reducing a c t i o n of carbon monoxide converts t h i s to the NH compound e i t h e r before or a f t e r c y c l i z a t i o n takes place.. 25 DISCUSSION A. Syn- ben z aldoxime The p r i n c i p a l e f f o r t of the present work was d i r e c t e d towards e s t a b l i s h i n g the f u r t h e r g e n e r a l i t y of the r e a c t i o n reported by Rosenthal et a l (4-0). These authors showed that c e r t a i n aromatic oximes reacted i n the presence of d i c o b a l t octacarbonyl and carbon monoxide at about 4100 p . s . i . and at 200 - 250° C to y i e l d lactams as shown i n equation I. R A / ^N - OH CO 8 I! 0 I This r e a c t i o n was successful where R was phenyl, methyl or benzyl (See i n t r o d u c t i o n page 23). In the present work syn-benzaldoxime, benzophenone oxime and the O-methyl ether of benzophenone oxime were allowed to r e a c t under the f o l l o w i n g conditions. The temperature range was 170° to 230° C 26 and i n i t i a l pressures were near 2200 p . s . i . Maximum pressure reached under reaction conditions was near 4500 p . s . i . The reactions were c a r r i e d out i n p u r i f i e d benzene so l u t i o n s i n the presence of preformed d i c o b a l t octacarbonyl. In the case of syn-benzaldoxime the following products were i s o l a t e d from the r e a c t i o n mixture; sym-dibenzylurea (35$), mono- benzylurea (1056), benzaldehyde (10#), compound A (15/0, compound B (15/0. By analogy with the above described established r e a c t i o n (40) phthalimidine could be expected as a product of t h i s r e a c t i o n . I t was not found possible to i s o l a t e any of t h i s compound. T o t a l recovery shown above i s &5%* I t i s believed that considerable amounts of organic materials were complexed with degradation products of the c a t a l y s t . An example of t h i s i s material I (see page 56 experimental section) which contained carbon, hydrogen and nitrogen as well as cobalt. Other examples o f i g n i t a b l e , c o b a l t containing, materials appear i n the experimental section. No c h a r a c t e r i z a t i o n work was done on compounds A and B since t h e i r i n f r a r e d spectra showed no absorption i n the carbonyl region and the p r i n c i p a l i n t e r e s t l a y i n the carbonylated compounds. These com pounds f a i l e d also to show absorption i n the OH or NH s t r e t c h i n g regions of the i n f r a r e d . The presence of benzaldehyde i n the r e a c t i o n mixture seems to i n d i c a t e that hydrolysis of the oxime has occurred. Care was taken to 27 use dry solvent and substrate but a small amount of water may have been present i n the carbon monoxide used. However the comparatively large y i e l d (10%) of benzaldehyde i n d i c a t e s some other method of pro ducing t h i s compound i s probable. This could have occurred i n some manner such as rearrangement of the oxime while complexed with the carbonyl c a t a l y s t . (OC^- C- it! / \ Co Co (CO), ph c I H N 'OH Formula I represents a hypothetical intermediate analogous to those established f o r alkynes and alkenes (4-6, 50, 24) (See i n t r o d u c t i o n page 10). I t was pointed out e a r l i e r ( introduction page 12) that some mechanism must e x i s t f o r the f a c i l e movement of hydrogen i n the com plexes suggested f o r o l e f i n reactions. Some analogous rearrangement i n v o l v i n g the hydroxyl group could produce benzaldehyde. The behaviour of the f i r s t m a t e rial eluted from the chroma tographic separation of the reaction products (see page 44 ) i s s i m i l a r to that reported f o r a complex with d i c o b a l t octacarbonyl by Greenfield 28 et a l (17). These authors l i s t e d the f o l l o w i n g properties f o r acetylenic d i c o b a l t hexacarbonyls; deep red c o l o r , weak intermolecular f o r c e s , high v o l a t i l i t y , high s o l u b i l i t y i n organic solvents and easy removal from activa t e d alumina. These properties are consistent with the behaviour of the eluted material mentioned above, since the material from the column f i r s t formed a homogeneous red alcohol s o l u t i o n . An attempt to i s o l a t e the d i s s o l v e d material produced a brown s o l i d i n s o l u b l e i n alcohol plus an organic component which has been r e f e r r e d to as Compound A. The brown s o l i d was shown to contain cobalt. G r e e n f i e l d e t a l also reported that b e n z i l was a major component i n the decomposition of diphenylacetylene d i c o b a l t hexacarbonyl at room temperature. This observation may p a r a l l e l the i s o l a t i o n of benzaldehyde as a reaction product. Mono-benzylurea and sym-dibenzylurea were i d e n t i f i e d by mixed melting point using authentic samples (8). These compounds also possessed i n f r a r e d spectra i d e n t i c a l with those of the authentic samples (pages A9 and 55 )• Sym-dibenzylurea was oxidized to produce sym- dibenzoylurea. This w r i t e r i s unable to postulate a reasonable mechanism f o r the formation of the observed substituted ureas. I t would be suf f i c i e n t to explain the production of mono-benzylurea since sym- dibenzylurea can be obtained from mono-benzylurea by heating and would be expected under the r e a c t i o n conditions i f mono-benzylurea were present (8). 29 I t may be mentioned that the h y d r o l y s i s information reported i s consistent with the behaviour of ureas. The a l k a l i n e conditions (page 50) should hydrolyze most amides (13) but higher temperatures and/or longer times are needed f o r ureas (42). I t i s worthy of note that each organic compound recovered from the chromatographic separation was accompanied by a yellow o i l y material. At f i r s t on r e c r y s t a l l i z l n g these compounds i t was f e l t that an oxidation was taking place. Sub sequent i s o l a t i o n of the yellow material, however, always showed the presence of cobalt. I t i s f e l t that the amides present may i n some manner be complexed with a cobalt compound and the complex decomposes f a i r l y slowly. Hieber (21) i n d i c a t e d amide complexes with d i c o b a l t octacarbonyl may be broken down i n r e f l u x i n g petroleum ether. In the f i r s t run of the syn-benzaldoxime r e a c t i o n the o v e r a l l absorption of carbon monoxide was 2.1 moles per mole of substrate. The rerun showed an absorption of 1.25 moles per mole of substrate. The second run was c a r r i e d out i n a new s t a i n l e s s s t e e l bomb without a glass l i n e r whereas the f i r s t run used a glass l i n e r . In s p i t e of t h i s d i f  ference i n carbon monoxide absorption the same organic components could be i s o l a t e d from both reactions. I t was impossible to compare r e l a t i v e y i e l d s because of an accident i n v o l v i n g shattering of a d i s t i l l i n g f l a s k containing the reaction product from run two. In each case the presence of d i c o b a l t octacarbonyl a f t e r completion of the r e a c t i o n was shown. The carbon monoxide used f o r the reactions contained 0.04 volume percent of hydrogen according to an analysis supplied by the 30 manufacturer (Matheson, New Jersey), Vapor phase chromatography c a r r i e d out i n t h i s department obtained a r e s u l t of 1.5$ by volume. Vapor phase chromatography of the product gases showed the absence of hydrogen. The conditions under which the sampling was done do not preclude the p o s s i b i l i t y that any hydrogen present had united with c a t a l y s t molecules rather than with the substrate. The sampling was done at room temperature and high pressure (2000 p . s . i . ) . Under these conditions cobalt hydro- carbonyl i s stable and does not decompose u n t i l the pressure i s released (33). I t was mentioned above that no phthalimidine could be detected i n the product mixture. I t i s possible that any phthalmidine formed condensed to more complicated products under the severe r e a c t i o n conditions since two uncharacterized products were present. I t i s suggested here that subjection of the O-methyl ether of benzaldoxime to the r e a c t i o n conditions may l e a d to r i n g closure since the methyl group may provide hindrance to competing reactions. This statement i s made considering the analogous case of the O-methyl ether of benzo phenone oxime where the only organic product was 3-phenylphthalimidine and the side product found with benzophenone oxime was not present. B. Benzophenone Oxime. In the r e a c t i o n with benzophenone oxime the major product (70$) was 3-phenylphthalimidine. A minor product (approximately 5%) 31 was the u n i d e n t i f i e d compound B. 3-Phenylphthalimidine was i d e n t i f i e d by d i r e c t comparison with an authentic sample (39). A mixed melting point showed no depression and t h e i r i n f r a r e d spectra were i d e n t i c a l . An acetate d e r i v a t i v e was also prepared. The reaction with benzophenone oxime was run with varying amounts of c a t a l y s t . In one t r i a l 0.07 moles of substrate and 0.02 moles of c a t a l y s t were used. In the second case 0.1 moles of substrate and 0.02 moles of c a t a l y s t were used. Case one showed an absorption corresponding to 1.75 moles of carbon monoxide per mole of substrate. Case two showed an absorption of 1.80 moles per mole of substrate. The composition of the recovered organic product d i d not seem to be a f f e c t e d by the d i f f e r e n c e i n substrate to c a t a l y s t r a t i o . However i n a t h i r d t r i a l the amount of c a t a l y s t was reduced to approximately 0.002 moles and a major d i f f e r e n c e i n the course of r e a c t i o n was noted (see page 3A). Also present i n t h i s reaction was cobaltous carbonate. The r e s u l t s of the r e a c t i o n i n d i c a t e that appreciable amounts of d i c o b a l t octacarbonyl were not formed from the cobaltous carbonate under the r e a c t i o n conditions. In both of the f i r s t two cases the recovery of organic material was near 75% of which roughly 5% was the u n i d e n t i f i e d component B. An exact y i e l d f o r compound B i s not a v a i l a b l e because no complete separation was c a r r i e d out. I t was noted that compound B was more soluble i n ether than 3-phenylphthalimidine. Therefore ether extractions of the t o t a l organic amount were c a r r i e d out to obtain a s o l u t i o n con t a i n i n g a l a r g e r proportion of compound B. This s o l u t i o n was then 32 chromatographed to separate B from remaining 3-phenylphthalimidine. I t was not possible to state how quantitative the ether separation was. I t was simple to obtain pure 3-phenylphthalimidine since r e c r y s t a l l i z a t i o n of the o r i g i n a l mixture from ethanol, methanol, or benzene would produce pure compound. Extensive t r i a l s of r e c r y s t a l - l i c a t i o n solvents f a i l e d to produce pure compound B. The behaviour of a mixture of B and 3-phenylphthalimidine was unusual when recrys t a l l i z a t i o n from ether was attempted. The f i r s t crop of c r y s t a l s was l a r g e l y 3-phenylphthalimidine the second was 60$ compound B and 40% 3-phenylphthalimidine. The t h i r d was l a r g e l y >phenylphthalimidine. These r e s u l t s were obtained through alumina chromatography (page 64 ). A reduction of compound B was c a r r i e d out using hydrogen over platinum oxide i n acetic acid s o l u t i o n . The products of t h i s reduction were compared to the products of a p a r a l l e l reduction of 3-phenylphthali midine. The major product f o r the reduction of 3-phenylphthalimidine was 3-cyclohexylhexahydro-phthalimidine ( H I ) as i s shown on page 6 3 C n 0 XII 33 A small sample (5% y i e l d ) of an i d e n t i c a l compound (mixed melting point and i n f r a r e d spectra) was secured from the reduction o f compound B. This same compound was also obtained by a p a r a l l e l reduction of an authentic sample of 3-phenylphthalimidine prepared by the method of Rose (39). These experiments provided e x t r a proof o f the i d e n t i t y of the 3-phenylphthalimidine produced. However the r e s u l t s are not believed to give an i n d i c a t i o n of the structure of compound B since the material used f o r the reduction i s not now considered pure. The compound B used was obtained by a r e c r y s t a l l i z a t i o n procedure and melted sharply at 197 - 199° G. The an a l y s i s obtained showed an empirical formula corresponding to a dimer of 3-phenylphthalimidine ^28 H22 N2^ )2 )• However subsequent chromatographic p u r i f i c a t i o n f a i l e d to change the melting point though i t d i d change the analysis so that the best f i t e m p i r i c a l formula became Cg^H^^^s* ^ p o s s i b l e explan ati o n of the observed phenomena i s that the compound B used f o r the reduction was contaminated with 3-phenylphthalimidine but that suf f i c i e n t s i m i l a r i t y i n c r y s t a l structure prevented lowering of the melting point. A summary of the properties of compound B follo w s : I t was soluble i n ether, benzene and alcohols. I t was i n s o l u b l e i n b o i l i n g water, b o i l i n g 20$ sodium hydroxide, or b o i l i n g concentrated hydrochloric acid. Conditions suitable f o r hy d r o l y s i s of a l l but the most hindered aromatic amides f a i l e d to a f f e c t compound B. Even though i t s i n f r a r e d 34 spectrum i n d i c a t e d active hydrogen stringent a c e t y l a t i o n conditions f a i l e d to a f f e c t the compound. (Fused sodium acetate refluxed i n a c e t i c anhydride f o r 6 hours). When the amount of c a t a l y s t was reduced to 0.002 moles ( t r i a l I I I ) the major product o f the re a c t i o n was benzophenone which was recovered i n 70$ y i e l d . Less than a 1$ y i e l d of 3-phenylphthalimidine was recovered and no trace of compound B was found. Also recovered from the reaction was 5$ of the o r i g i n a l oxime. This i n d i c a t e s that con version of the oxime to benzophenone i s a slow process since some o r i g i n a l oxime was recovered a f t e r 4 hours heating. C. 0-Methyl Ether of Benzophenone Oxime. The O-methyl ether of benzophenone oxime was subjected to the react i o n conditions i n an attempt to produce an N-substituted c y c l i c compound i n accordance with equation I C = N-OCH, co Co 2(C0)g N-OCH, However the r e s u l t i n g product was a 70$ y i e l d of 3-phenylphthalimidine, Only a trace of another organic component could be found. 35 I t i s of i n t e r e s t that on washing an alumina column with acetone a f t e r e l u t i o n of the reaction products a l i g h t brown o i l was obtained which was obviously (judging from quantity) not a product o f the reaction. This material reacted instantaneously with i c e co l d 2% potassium permanganate and with bromine i n carbon t e t r a c h l o r i d e . The b o i l i n g point of the material was 163 - 166° C (corrected). The l i t e r  ature value f o r diacetone alcohol i s 164. - 166° C. D. Discussion of Pressure P l o t s D e t a i l e d records were kept of the v a r i a t i o n of pressure with time and temperature f o r a l l reactions. Plots f o r each substrate used are shown on pp 42, 66, 73. The p l o t s show v a r i a t i o n of pressure with r e a c t i o n time at constant temperature. A l l pressures are corrected to 0° C. A l l pressures are corrected f o r the vapor pressure of the benzene solvent. The assumption I s made that the v a r i a t i o n s i n pressure remaining a f t e r these corrections are due to absorption or release o f carbon monoxide. I t i s r e a l i z e d that the s o l u b i l i t y of carbon monoxide In the l i q u i d phase may change with temperature i n the closed system. However t h i s cannot account f o r the sudden changes i n pressure noted at f a i r l y constant temperature. Another p o s s i b i l i t y i s that some other gas besides carbon monoxide i s released i n the system. This could best be checked by sampling the gases at the peak of the pressure curve. This procedure i s d i f f i c u l t and dangerous with the present equipment due to the high t o x i c i t y of carbon 36 monoxide and cobalt carbonyls and the high r e a c t i o n pressures and temperatures. However a reducing valve could be i n s t a l l e d f o r t h i s purpose. P l o t s o f the nature submitted would be of more d e f i n i t e value i f the benzene s o l u t i o n containing c a t a l y s t could be heated to r e a c t i o n temperature with carbon monoxide under pressure before i n j e c t i o n of the substrate. I f the r e a c t i o n were then c a r r i e d out at constant temperature any pressure v a r i a t i o n s could d e f i n i t e l y be ascribed to be r e s u l t s of the r e a c t i o n . I t should be mentioned that carbon monoxide may be treated as an Ideal gas throughout the pressure temperature range involved. This was established by use of the reduced pressure reduced temperature approximation. Comparison of the p l o t s f o r benzophenone oxime (page 66) and i t s 0-methyl ether (page 73) shows both materials cause a release of carbon monoxide at low temperatures (20 to 55° C), nearly 2i moles per mole of substrate i n the case of the ether, but only 0.6 moles f o r the oxime i t s e l f . Both of these f i g u r e s are minimums f o r two reasons. F i r s t the carbon monoxide r e l e a s i n g reaction may have taken place p a r t l y while the carbon monoxide was being added. The i n i t i a l pressure could not be measured u n t i l a l l the added gas was present and some time had to be allowed f o r s o l u b i l i t y e q uilibrium to be reached. Secondly there i s l i t t l e d e t a i l on the p l o t s i n t h i s area so the actual maximum may not have been recorded. In the case of syn-benzaldoxime no points were recorded i n the corresponding area. Since s t e r i c hindrance plays an 37 important part i n the rate of formation of complexes (see page 13) i t i s f e l t that the O-methyl ether should form a complex l e a s t r e a d i l y and therefore part of the i n i t i a l pressure recorded i n the cases of benzophenone oxime and syn-benzaldoxime may a c t u a l l y have come from the r e a c t i o n of the substrate and c a t a l y s t . This conjecture could be checked by e q u i l i b r a t i n g the r e a c t i o n mixture at constant temperature before i n j e c t i o n of the substrate. A U the p l o t s show that any gas released i s q u i c k l y reab sorbed. The O-methyl ether p l o t remains comparatively near the o r i g i n a l pressure value once the temperature reaches 165° G' u n t i l the heating element was turned o f f . A f t e r t h i s point i t shows an absorption of 1 mole of carbon monoxide per mole of substrate. This phenomenon could correspond to some rea c t i o n absorbing carbon monoxide or to the conden sation of some unknown gaseous component. The benzaldoxime shows s i m i l a r behaviour i f the assumption i s made that o r i g i n a l complex formation was very rapid and that the o r i g i n a l pressure recorded already includes the carbon monoxide released by the complexing action. The benzophenone p l o t shows remarkable pressure changes from the point where the temperature reaches 160° C. There i s a sudden evolution of 1 mole of carbon monoxide followed by a sudden absorption of 2 moles. A l l t h i s takes place i n 5 minutes. No explanation can be o f f e r e d f o r t h i s i n t e r e s t i n g phenomenon. I t i s r e a l i z e d the pressure peak at the 37 minute mark i s evidenced by only one point but the 38 behaviour was obtained on a second t r i a l and the phenomenon also appears i n the work of Hubscher (22). At l e a s t two examples appear i n t h i s work of cobalt containing compounds which were soluble i n benzene and l o s t t h e i r s o l u b i l i t y i n t h i s solvent a f t e r r e f l u x i n g i n l i g h t petroleum ether. This behaviour could be s i m i l a r to that reported by Hieber (21) and mentioned on page 39 EXPERIMENTAL A. General A l l i n f r a r e d spectra reported were obtained using a Perkinr: Elmer Model 21 spectrometer i n t h i s department except f o r the spectrum of the reduced product of 3-phenylphthalimidine which was obtained on a Baird-Atomic spectrometer i n the F o r e s t Products Laboratory. The vapor phase chromatography was c a r r i e d out on equipment constructed i n t h i s department. A l l alumina used f o r chromatography was B r i t i s h Drug Houses chromatographic grade ca l c i n e d alumina. Elemental analyses were c a r r i e d out by Dr. A. Bernhardt of the Max Planck I n s t i t u t e , Mulheim, Ruhr, Germany. Melting points were determined using a p o l a r i z i n g microscope on an e l e c t r i c a l l y heated hot stage. Corrected melting points were read d i r e c t l y . Acknowledgement i s hereby expressed to Mr. Harold Maclean of the Forest Products Laboratory and Mrs. M l of t h i s department f o r i n f r a r e d determinations and to Dr. S. Ryce and Mr. S. Ruzicka of t h i s department f o r vapor phase chromatography. AO B. Reaction of Syn-benzaldoxime with Carbon Monoxide i n the Presence of D i c o b a l t Octacarbonyl, a. Preparation of reactants Syn-benzaldoxime was prepared according to the method of Beckmann (2);. The y i e l d obtained was 31% of pure product based on benzaldehyde. An i n f r a r e d spectrum i n chloroform sol u t i o n was obtained as a check on the p u r i t y of the aldoxLme (34-) and f o r comparison with reaction products, D i c o b a l t octacarbonyl was prepared according to the method of Wender et a l (54-), The c a t a l y s t was not i s o l a t e d but was used d i r e c t l y i n the benzene s o l u t i o n i n which i t was obtained. The c a t a l y s t prepared i n t h i s manner contains 0.25 gm or 7.3 x 10"^ moles per ml. S p e c i a l l y d r i e d and p u r i f i e d thiophene-free benzene was used both to prepare the c a t a l y s t and to carry out the reactions. The carbon monoxide used contained 1.5$ by volume of hydrogen as determined by vapor phase chromatography. Ah a n a l y s i s supplied by the Matheson Company from whom the carbon monoxide was purchased i n d i c a t e d a hydrogen percentage of 0.0A% by volume. The analysis here was c a r r i e d out by comparing the observed peak height of 100$ hydrogen with the hydrogen peak from the carbon monoxide, A better procedure would have been to use a known mixture c l o s e r i n composition to the unknown. This may have given r e s u l t s c l o s e r to the Matheson f i g u r e . b. Reaction procedure. The re a c t i o n was c a r r i e d out i n a glass l i n e d Aminco super-41 pressure r e a c t i o n vessel which was equipped with a rocker mechanism. Temperature c o n t r o l was achieved through a Brown pyrometer using a thermocouple which had been c a l i b r a t e d against a standard thermometer. An amount of 6.5 gm of syn-benzaldoxime (0.054 mole) was placed i n the glass l i n e r with 25 ml of c a t a l y s t s o l u t i o n (0.02 mole). A homogeneous solu t i o n r e s u l t e d . P u r i f i e d benzene was added to make the t o t a l volume 60 ml and the l i n e r placed i n the r e a c t i o n vessel ( e f f e c  t i v e void 180 ml). The sealed v e s s e l was flushed twice with carbon monoxide to remove a i r . Carbon monoxide was run i n to a t o t a l pressure of 2300 p . s . i . at 12° C (2200 p . s . i . at 0° C). Heating was then commenced. The Thermostat was set at 170° C and the temperature rose to t h i s point i n 39 minutes. A f t e r 6 minutes at t h i s temperature the l a c k of v a r i a t i o n i n the observed pressure i n d i c a t e d no reaction, so the temperature was r a i s e d i n steps of ten degrees to 220° G. The :temperature was held at each ten degree l e v e l f o r 6 to 8 minutes. F i n a l l y the temperature was maintained at 220° C f o r 17 minutes before turning o f f the heating element. The t o t a l elapsed time from s t a r t to end of heating was 100 minutes. The re a c t i o n v e s s e l was then allowed to cool to room temperature overnight. The f i n a l pressure observed was 2070 p . s . i . at 11° C (1990 at 0° C). This i s an o v e r a l l drop of 210 p . s . i . at 0° G and corresponds to 0.115 mole of carbon monoxide which i s 2.1 moles per mole of substrate or 5.8 moles per mole of c a t a l y s t . A d e t a i l e d record of pressure time and temperature was kept and the r e s u l t s plotted on page 42, T O T A X L H ^ - ^ cT P R E S S U R E C o « « t c T t ? • to 0 ° C F O R S x t ^ - 6 E N Z A V . O O / \ M E 0 . 0 5 4 - O . O Z N\oi_es M O L E S 2300- - N o t e . : V o R V ^ V o u « V^E.'S'_\--{._. 2 0 0 0 \ 9 0 0 8 0 \55 \70 L- 0 V85 2 0 5 _J I L_ 20 40 60 80 \CO T\w\e \M W\\NUTSS oo 1 0 k 0 0 V- 0 43 The reaction product was a brown homogeneous so l u t i o n . This s o l u t i o n was evaporated at 25 - 35° C using a water a s p i r a t o r to remove any unchanged c a t a l y s t and the benzene solvent. c. Separation and i d e n t i f i c a t i o n of products The reaction product a f t e r removal of the benzene was a green t a r r y material. I t dissolved completely i n warm benzene to a s o l u t i o n of 51 ml t o t a l volume. A 3 ml a l i q u o t of t h i s s o l u t i o n was placed on an alumina column (12-& cm x 3 cm diameter) f o r chromatography. The r e s u l t s f o r t h i s a l i q u o t (one seventeenth of the t o t a l r eaction product) are d e t a i l e d on page 44. ( i ) F i r s t f r a c t i o n from chromatogram (compound A) On commencing e l u t i o n with benzene a purple band moved q u i c k l y down the column and resulted i n a red benzene s o l u t i o n . On standing the color of t h i s s o l u t i o n gradually changed to brown. Evaporation of the solvent l e f t a mixture of white and brown s o l i d s . Addition of ethanol produced a red colored ethanol s o l u t i o n and l e f t a white crys t a l l i n e residue. This white material was e a s i l y soluble i n benzene leav i n g the brown residue. This brown residue f a i l e d to melt at 350° C and l e f t a cobalt-containing residue on i g n i t i o n . The white material was r e c r y s t a l l i z e d from petroleum ether and melted at 239 - 242° G -with some change i n c r y s t a l structure near 220 - 225° C. The i n f r a r e d spectrum of t h i s material (compound A) showed no absorption i n the 44 Chromatography of Reaction Product of Syn-benzaldoxime (Aliquot containing one-seventeenth of r e a c t i o n product) Eluent Benzene Benzene Benzene Benzene Benzene ethanol 99 r l Benzene ethanol 99 r l Benzene ethanol 98*2 Benzene ethanol 98:2 Benzene ethanol 9812 Benzene ethanol 98 tZ Amt. used i n ml 0-125 125-175 175-325 325-775 775-875 875-1075 1075-1225 Product Compound A Nothing Compound B Nothing Nothing Compound C Nothing Des c r i p t i o n Weight i n mgm 1275-1325 Nothing p u r p l i s h o i l y c r y s t a l s odor of benzaldehyde white c r y s t a l s yellow o i l y m a t e rial plus white c r y s t a l s 1075-1225 Nothing 1225-1275 Compound D yellow o i l 40 40 120 2 7 Further washings with 200 ml benzene ethanol 50:50, 200 ml o f absolute ethanol, and 200 ml of acetone produced nothing. Apparent organic y i e l d from a l i q u o t 227 mgm Total apparent y i e l d 3.86 gm 45 carbonyl region so no f u r t h e r work was done on i t . The i n f r a r e d spectrum (potassium bromide d i s c ) showed the following major absorp t i o n peaks: 3050W> 1598sh, 1589W, 1523S, 1369S, 1301W, 1175W, 1069W, 1029W, 843M, 746S, 686S, 648M. The i n f r a r e d spectrum i s reproduced on page 46. ( i i ) Second f r a c t i o n from chromatogram (Compound B) This f r a c t i o n appeared white but picked up a yellow c o l o r during evaporation of the solvent (water a s p i r a t o r l e s s than 35° C). Melting range of the crude material was 100 - 230° C. L i g h t petroleum ether d i s s o l v e d the yellow material l e a v i n g a white residue which melted at 280 - 282° G a f t e r two r e c r y s t a l l i z a t i o n s from 30 - 60° C petroleum ether. The i n f r a r e d spectrum of compound B f a i l e d to show absorption i n the carbonyl region so no f u r t h e r work was done on i t . The i n f r a r e d (potassium bromide d i s c ) showed the fol l o w i n g major ab sorptions: 3055W, 1601W, 1579W, 1507W, 1492M, 1465M, 1447W, 1414W, 1400W, 1325W, 1204W, 1153W, 1072W, 973W, 917W, 767M, 736M, 714M, 698S. ( i i i ) Third f r a c t i o n from chromatogram (sym-dibenzylurea) This f r a c t i o n also consisted of a white material with some yellow. The yellow c o l o r was s l i g h t l y soluble i n l i g h t petroleum ether and very soluble i n ether. White c r y s t a l s were s l i g h t l y soluble i n e i t h e r solvent. Crude material was extracted with ether and 30 - 60° C petroleum ether to leave a white material melting at 160 - 167° C Infrared spectrum (potassium bromide disc) Compound A 4 o e » o — I 3 o o o 2 0 O O \9 \a \1 \€» \5 \A- \3 va. w \ooo 3 -t-1 48 (Compound C). Compound C dis s o l v e d f a i r l y r e a d i l y i n benzene and l e f t a small amount of green residue. This green material contained cobalt and f a i l e d to melt at 310° C I t dis s o l v e d r e a d i l y i n concentrated hydrochloric acid to a green sol u t i o n . On d i l u t i o n and treatment with sodium hydroxide the presence of cobalt was proven. Compound C was now r e c r y s t a l l i z e d from benzene petroleum ether and melted at 168 - 169^"° C. The i n f r a r e d spectrum (potassium bromide d i s c ) showed the following major absorptions: 3337S, 3043W, 2922W, 1625S, 1591S, 1575S, 1497W, 1475W, 1458M, 1435W, 1369W, (1275 to 1225 broad absorption), 1080S, 1027W, 757W, 733W, 698S. The i n f r a r e d spectrum I s reproduced on page 49. Compound C was soluble i n benzene, alcohol, ether, but very l i t t l e i n l i g h t petroleum ether. The compound was i n s o l u b l e i n cold water but dissolved slowly i n hot concentrated sodium hydroxide. I t was i n s o l u b l e i n cold concentrated hydrochloric a c i d but slowly d i s  solved on heating to a l i g h t yellow colored s o l u t i o n . No p r e c i p i t a t e could be obtained from e i t h e r the basic or a c i d i c s o l u t i o n s by ne u t r a l  i z i n g with hydrochloric a c i d or sodium hydroxide r e s p e c t i v e l y . Compound C was soluble i n concentrated sulphuric a c i d and no pr e c i p i t a t e was obtained on d i l u t i o n with water. The a c i d solutions above were extracted with benzene. The material recovered proved i d e n t i c a l with o r i g i n a l by mixed melting point. Infrared spectrum (potassium j 1 bromide disc) I/ sym-dibenzylurea ( _____) \i sym-dibenzoylurea (— - =) —I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 30OO 2000 IS \8 \7 \€> \50O \4 V3 U U \000 <3 e> 7 6oo S 50 Compound C was now heated at r e f l u x temperature f o r f o r t y hours i n 20$ sodium hydroxide i n ethanol water. On n e u t r a l i z a t i o n with hydrochloric a c i d c r y s t a l s were obtained i d e n t i c a l to o r i g i n a l by mixed melting point. Ah attempt to prepare an acetate d e r i v a t i v e under the f o l  lowing conditions produced an o i l . An amount of 5 mgm of compound C was refluxed f o r four hours with fused sodium acetate (50 mgm) and 5 ml of a c e t i c anhydride. On pouring the a c e t y l a t i n g mixture onto i c e a small amount of o i l which was i n s o l u b l e i n hot water was obtained. This o i l was not c r y s t a l l i z a b l e from the common solvents. An amount of 50 mgm of compound C was heated on a steam bath i n concentrated hydrochloric acid r e s u l t i n g i n a l i g h t l y yellow colored s o l u t i o n . Aqueous d i l u t i o n of t h i s acid s o l u t i o n produced a milky appearance with some curdy white material. Ether e x t r a c t i o n removed the milky appearance. Evaporation of the ether l a y e r r e s u l t e d i n recovery of the o r i g i n a l m aterial. Yellow c o l o r a t i o n shows s l i g h t h ydrolysis. Ah amount of 10,8 mgm of compound C was now refluxed f o r 6 hours with concentrated hydrochloric acid. The s o l u t i o n was d i l u t e d to 6 normal and allowed to stand overnight. No c r y s t a l s appeared. An ether e x t r a c t of t h i s s o l u t i o n contained nothing. The aqueous l a y e r was now n e u t r a l i z e d with sodium hydroxide. There was no immediate p r e c i p i t a t e but on standing overnight a f l o c c u l e n t p r e c i p i t a t e appeared. This material was extracted with chloroform. Again the material i s o l a t e d was the o r i g i n a l . 51 The aqueous l a y e r remaining a f t e r the chloroform e x t r a c t i o n was extracted with ether. The ether contained nothing. Oxidation of phthalimidine was now attempted to develop a su i t a b l e oxidation procedure f o r compound C. The phthalimidine was prepared from phthalimide by the method of Graebe (18). An i n f r a r e d spectrum of phthalimidine was obtained f o r comparison with r e a c t i o n products. An amount of 239 mgm of phthalimidine was dissolved i n 50 ml of g l a c i a l a c e t i c acid. One gm of s o l i d sodium dichromate was added slowly while the s o l u t i o n was heated strongly on a steam bath. Reflux was c a r r i e d out f o r 4 hours a f t e r completion of the dichromate addition. The reaction mixture was poured i n t o 50 ml of water r e s u l t i n g i n a homogeneous s o l u t i o n . This aqueous s o l u t i o n was extracted with chloro form to y i e l d a residue of an a c e t i c a c i d s o l u t i o n . Addition of water to the a c e t i c a c i d produced c r y s t a l s . These were redissolved i n chloro form and the chloroform was washed with water to get r i d of most of the a c e t i c a c i d and again evaporated. Water added now again caused p r e c i  p i t a t i o n of c r y s t a l s which were now r e c r y s t a l l i z e d d i r e c t l y from water. The material d i s s o l v e d slowly i n b o i l i n g water and r e c r y s t a l l i z e d r a p i d l y on cooling (m.p. 236 - 238° C with softening at 230° G-). This behaviour i s exact f o r phthalimide. A mixed melting point showed no depression. Y i e l d was 79$ of r e c r y s t a l l i z e d product. Sixty-three mgm of compound C were now oxidized under the same conditions using 25 ml of g l a c i a l a c e tic a c i d and 0.3 gm of sodium dichromate. The o x i d i z i n g mixture was extracted d i r e c t l y with chloroform. 52 Treatment as above yi e l d e d 42 mgm of a product melting at 202 - 203° C a f t e r two r e c r y s t a l l i z a t i o n s from ethanol water. The i n f r a r e d spectrum (potassium bromide d i s c ) of t h i s oxidized product i s shown on page 4-9 compared to compound C. The major absorption peaks were measured as follows: 3240W, 1753S, 1670S, 1603W, 1577W, 1534M, 1506M, 1480M, 1288M, 1266S, 1200M, 1192W, 1067W, 771M, 696S. This product d i d not re a c t with sodium bicarbonate and was not an acid. The product d i s s o l v e d very r e a d i l y i n acetone but required warming to d i s s o l v e i n ethanol. I t was dissolved by b o i l i n g water. The product was small well formed needles. The aqueous l a y e r from the oxidation reaction remaining a f t e r chloroform extraction was now a c i d i f i e d with sulphuric acid since an acid stronger than a c e t i c a c i d i f formed i n the reaction would not otherwise be extracted by organic solvents. Now sodium b i s u l f i t e was added to destroy excess oxidant. Ether e x t r a c t i o n of the r e s u l t i n g green acid s o l u t i o n recovered 5 mgm of an organic acid which was e a s i l y soluble i n ether, ethanol or benzene, but soluble l e s s r e a d i l y i n l i g h t petroleum ether. The acid f a i l e d to c r y s t a l l i z e from l i g h t petroleum ether but r e c r y s t a l l i z e d from water at 0° C. A f t e r 2 r e c r y s t a l l i z a t i o n s m.p. was 120 - 122° C. Mixed melting point with an authentic sample of benzoic a c i d was 120 - 122° Q. Thionyl chloride was added to 3 mgm of dry material from above and refluxed on steam bath f o r one-half hour. Mixture was poured i n t o 1 ml of cold concentrated ammonium hydroxide. A p r e c i p i t a t e separated and was washed with water. The p r e c i p i t a t e was dissol v e d i n ethanol and p r e c i p i t a t e d out with water. Melting point was 126 - 127° C. L i t e r a t u r e f o r benzamide i s 127° G; 53 Analysis c a l c u l a t e d C, 75.00; H, 6.67j N, 11.67; f o r C 1 5H l 6N 2p i Mol. wt. 240 Found C, 74.87; H, 6.79; N, 11.91; Mol. wt. (Rast) 263 The high amount of hydrogen suggests a l i n e a r structure and the i n f r a r e d of the oxidation product demands 2 d i f f e r e n t carbonyls. Sym-dibenzylurea f i t s m.p., analysis, i n f r a r e d , s o l u b i l i t y , and hydro l y s i s information. So an authentic sample was prepared according to the procedure of Davis and Blanchard (8). This authentic sample proved to have an i d e n t i c a l i n f r a r e d spectrum with compound C. No depression was obtained i n a mixed melting point determination. The oxidized product must now be sym-dibenzoylurea whose m.p. i s 203° C as reported by B i l t z (5). No explanation i s offered here f o r the melting point of 208° C reported by B i l l e t e r (4). ( i v ) Fourth f r a c t i o n from chromatogram (mono-benzylurea) Compound D was also accompanied by a yellow o i l y material. Repeated r e c r y s t a l l i z a t i o n from benzene - petroleum ether was required to produce a pure sample which melted at 147 - 149° C. The i n f r a r e d spectrum i n a potassium bromide d i s c showed the fo l l o w i n g major absorptions; 3440S, 3323S, 3035W, 2922W, 2876W, 1651S, 1601S, 1564S, 1499W, 1471M, 1458M, 1389M, 1338W, 1329W, 1312W, 12C9W, 1144M, 1109M, 54 1079W, 1027W, 758M, 752M, 697S. This spectrum i s reproduced on page 55. Since the expected product of the reaction was phthalimidine (melting point 150° G), by analogy to previous work of Rosenthal e t a l (40) immediate comparison was made with an authentic sample of phthalimidine (18). The i n f r a r e d spectra were considerably d i f f e r e n t and a mixed melting point showed 25° C depression so that compound D was not phthalimidine. The i n f r a r e d spectrum of D strongly suggested the presence o f a primary amine or amide since i t showed strong ab sorption at 3440, 3328, 1601, and 1564. S o l u b i l i t y considerations ruled out the amino group and presence of an apparent carbonyl f u n c t i o n at 1651 cm""'' supported the primary amide. The carbonyl f u n c t i o n f a i l e d to react with 2, 4, dinitro-phenylhydrazine thus confirming the amide hypothesis. Since sym-dibenzylurea may be obtained from mono-benzylurea by simple heating, a sample of mono-benzylurea was prepared (8), Mixed melting point and comparison of i n f r a r e d spectra showed compound D to be i d e n t i c a l with mono-benzylurea, d. Repeat of rea c t i o n between carbon monoxide and syn-benzaldoxime i n the presence of d i c o b a l t octacarbonyl, Syn-benzaldoxime and d i c o b a l t octacarbonyl were prepared and reacted as on page 40, A sample of the product gases was analyzed by vapor phase chromatography. The only gas detected was carbon monoxide showing any hydrogen o r i g i n a l l y present had reacted. The pressure drop observed corresponded to the absorption of 0.075 moles of carbon monoxide. W A V E . N V I M \ ^ ^ - ^ S NT* C V \ " ' 56 Since 0.06 moles of substrate were used t h i s i s 1 .25 moles per mole of substrate. The r e a c t i o n product was a homogeneous dark brown benzene sol u t i o n . This s o l u t i o n was evaporated under vacuum (water a s p i r a t o r ) at l e s s than 35° C to remove or decompose any unreacted c a t a l y s t and benzene solvent. The d i s t i l l a t e was a l i g h t yellow benzene s o l u t i o n containing excess c a t a l y s t . The s o l i d residue appeared black i n c o l o r . The residue was extracted twice with b o i l i n g chloroform. This l e f t a dark green (cobalt containing) residue and a brownish green so l u t i o n . This residue was now extracted with b o i l i n g acetone and appeared p a r t l y soluble. F i l t r a t i o n of the acetone a f t e r c r y s t a l  l i z a t i o n produced a l i g h t green s o l i d (material I ) (0.4 gm) which i g  n i t e d i n a flame and l e f t a c o b a l t containing residue. This s o l i d was stable at 350° C on the melting point s l i d e . I t d i s s o l v e d i n hydro c h l o r i c a c i d to a b r i g h t green s o l u t i o n without effervescence but was i n s o l u b l e i n water. The i n f r a r e d spectrum of m a t e r i a l I was determined and f a i l e d to show absorption a t t r i b u t a b l e to the carbonyls of a cobalt carbonyl compound (33). Analysis of material I f a i l e d to show any simple r e l a t i o n s h i p between the constituents. Founds Co, 31.26; C, 12.28;, N, 2.99; H, 2.75. Further e x t r a c t i o n of the residue with r e f l u x i n g acetone dissolved nothing and l e f t a green i n s o l u b l e material (material I I ) (2.3 gm) which was s i m i l a r i n appearance to material I and also i g n i t e d 57 i n the flame t e s t leaving a black cobalt residue. The above chloroform s o l u t i o n containing organic products was evaporated to leave a green residue which was repeatedly extracted with r e f l u x i n g petroleum ether (30 - 60° C). The petroleum ether was colored wine straw and on cooling became opalescent. The green residue remained unchanged i n appearance. Evaporation of the petroleum ether s o l u t i o n y i e l d e d 0.8 gm of a brown viscous l i q u i d whose smell resembled benzaldehyde. Saturated aqueous sodium b i s u l p h i t e was added and some i n  soluble c r y s t a l s extracted with ether. On addition of the ether a very small amount of cobalt containing v i o l e t m a t erial separated. This was f i l t e r e d o f f and discarded. The ether l a y e r on evaporation produced 5 mgm of a material which melted at 229 - 230° C with a change i n c r y s t a l structure at 210 - 215° C a f t e r r e c r y s t a l l i z a t i o n from alcohol. This was shown i d e n t i c a l by mixed melting point with Compound A (page 43). The aqueous l a y e r was a c i d i f i e d with hydrochloric acid and warmed to destroy the b i s u l p h i t e . 2, 4-Dinitrophenylhydrazine reagent was added and an immediate yellow p r e c i p i t a t e was formed (0.54 gm) m.p. 235 - 237° C. Mixed m.p. with an authentic sample of benzaldehyde 2, 4-dinitrophenylh.ydrazone was 235 - 237° C. The green residue from the petroleum ether extraction was now extracted with benzene and a v i o l e t s o l i d was found to be i n s o l u b l e (1.6 gm). The major part of the organic product was now contained i n 58 the benzene solu t i o n . On standing 0.4 gm of white c r y s t a l s p r e c i p i t a t e d . Chromatography of a small sample of these c r y s t a l s showed them to be a mixture of compound C and compound D (pages 41 and 53). The green benzene s o l u t i o n on evaporation y i e l d e d 2.26 gm of a brown o i l which di s s o l v e d completely i n 15 ml of cold benzene f o r chromatography. Chromatography of the above benzene s o l u t i o n on alumina ( 7 i x 10 cm) gave the f o l l o w i n g r e s u l t s . Eluent Benzene Benzene Benzene ether 50 :50 Benzene ether 50:50 Benzene ether 50*50 Benzene ether 50:50 Benzene ether 50:50 Ethanol Ethanol Ethanol Amount 0 - 4 0 0 400 - 800 0 - 4 0 0 400 - 800 800 - 1000 1000 - 1200 1200 - 1400 0 - 500 500 - 700 700 - 1000 compound A 130 mgm m.p. 244 - 245° C nothing nothing compound B 100 mgm m.p. 2 8 7 i - 289° C nothing yellow o i l 0.2 gm nothing compound C 0.4 gm m.p. 165 - 172 C nothing brown o i l 1.1 gm The f i n a l f r a c t i o n from t h i s chromatographic separation was shown by r e c r y s t a l l i z a t i o n to contain cobalt and 0.2 gm of compound D. 59 Y i e l d from chromatogram was 1.93 gm from 2.3 added. To t a l o v e r a l l y i e l d of organic material from the r e a c t i o n was 5.2 gm. C. Action of Carbon Monoxide on Benzophenone Oxime i n the Presence of Di c o b a l t Octacarbonyl. a. Preparation of benzophenone oxime A mixture of 20 gm of benzophenone, 20 gm of hydroxylamine hydrochloride, 20 ml of pyridine and 200 ml of ethanol was refluxed on a steam bath f o r four hours. The alcohol was then removed by d i s t i l l a t i o n to leave a syrupy mixture. This mixture was cooled i n an i c e bath and 150 ml of water added slowly with s t i r r i n g . The r e s u l t i n g c r y s t a l s were r e c r y s t a l l i z e d twice from ethanol water. Y i e l d a f t e r two r e c r y s t a l l i z a t i o n s was 13.5 gm (62$ of t h e o r e t i c a l ) (m.p. U 3 - 1A5° C). L i t e r a t u r e 144° C. b. Reaction procedure The c a t a l y s t was prepared as on page 40 and rea c t i o n was c a r r i e d out i n e s s e n t i a l l y the same manner. Thirteen gm (0.07 mole) of benzophenone oxime and 25 ml of c a t a l y s t s o l u t i o n were used (0.02 moles). O r i g i n a l pressure ima 2210 p . s . i . corrected to 0° C, f i n a l pressure was 1990 p . s . i . corrected to 0° C. This i s an absorption of 0.12 mole o f carbon monoxide or 1.75 moles per mole of substrate. 60 T o t a l heating time was seventy-two minutes. c. Separation and i d e n t i f i c a t i o n of the products The glass l i n e r contained c r y s t a l l i n e material and a brown benzene solu t i o n . The benzene was evaporated at 25 - 35° C to leave brown c r y s t a l s . Some unreacted d i c o b a l t octacarbonyl d i s t i l l e d with the benzene to produce an orange colored s o l u t i o n . Solution of the brown c r y s t a l s i n hot chloroform produced a deep blue s o l u t i o n . Norite was added and the solu t i o n f i l t e r e d , hot a f t e r a few minutes r e f l u x . The so l u t i o n retained the blue c o l o r . Some pink material remained with the n o r i t e . The chloroform s o l u t i o n was cooled and white c r y s t a l s separated which melted 197 - 210° C (material I ) . R e c r y s t a l l i z a t i o n from chloroform f a i l e d to change t h i s melting range. A l l common solvents were used i n an attempt to f i n d a sui t a b l e r e c r y s t a l l i z a t i o n solvent. Repeated r e c r y s t a l l i z a t i o n of the material from benzene or from ethanol gave c r y s t a l s melting at 225 - 227° G. Ma t e r i a l I was extracted i n a Soxhlet apparatus f o r 4 hours using ether. An ether i n s o l u b l e residue (20 mgm) melted at 280 - 284° C (compound A). Evaporation of the ether so l u t i o n gave c r y s t a l s melting at 198 - 230° C (Material I I ) . M a t e r i a l II was white f l u f f y needles which gave a red c o l o r with concentrated sulphuric acid d i s s o l v i n g to a l i g h t yellow s o l u t i o n . 61 D i l u t i o n destroyed the c o l o r and r e p r e c i p i t a t e d white material. Con centrated hydrochloric a c i d showed a green c o l o r a t i o n and formic a c i d produced a red color. I t was noted that these same colors can be produced by a c t i o n of the above reagents on cobaltous s a l t s . Ah ether s o l u t i o n of material II was p a r t i a l l y evaporated and the r e s u l t i n g c r y s t a l s separated. These r e c r y s t a l l i z e d from methanol three times s t i l l gave above col o r s with acids. Melting point of t h i s material was 197 - 199° C (compound B). Reaction of the material with a c e t i c anhydride and sodium acetate under anhydrous conditions produced l i g h t yellow c r y s t a l s which melted at 197 - 199° C. A n a l y t i c a l r e s u l t s on compound B were: C, 80.21; H, 5.35; N, 6.53; Mol. wt. 380 Calculated f o r C 2 7 H 2 2 N 2 ° 2 ! C, 79.80; H, 5.40; N, 6.89; Mol. wt. 406 Calculated f o r C 2 8 H 2 2 N 2 0 2 : C, 80.38; H, 5.26; N, 6.70; Mol. wt. 418 Repeated r e c r y s t a l l i z a t i o n from methanol of that part of material I I which seemed l e a s t soluble i n ether gave c r y s t a l s melting at 225 - 227° C (compound C), Compound C was compared with an authentic sample of 3-phenylphthalimidine (39) and found to be i d e n t i c a l through i n f r a r e d spectrum and mixed melting point. The acetate d e r i v a t i v e melted at 153 - 154° C; l i t e r a t u r e m.p. 154° C (39). 62 Analysis of compound C: Calculated f o r C, 80.38; H, 5.27; N, 6.70; G H H 1 1 N 0 M o 1 , 2 0 9 Found: C, 80.35; H, 5.56; N, 6.65; Mol. wt. (Rast) 226 Compound B was reduced using the following experimental con d i t i o n s ; compound B (63 mgm) (.0015 moles), 17 mgm of platinum oxide i n 25 ml of g l a c i a l a c e t i c acid. Hydrogen was added at atmospheric temperature and pressure (64..4 ml) (.003 moles of hydrogen were absorbed i n 5^ hours). The hydrogen was absorbed r a p i d l y i n i t i a l l y and then at a steady rate. No s i g n i f i c a n t change i n the rate of hydrogen absorption could be detected at any time. The material l e f t a f t e r evaporation of solvents melted at 100 to 210° C. This material was d i s s o l v e d i n benzene f o r chromatography using an alumina column (1^" x 4"'). The " f i r s t 120 ml of benzene eluent produced nothing. The next 40 ml produced a yellow o i l from which hot l i g r o i n extracted white c r y s t a l s (material B 1, m.p. l e s s than 110° C). Further benzene (100 ml) and benzene containing 2% ethanol (100 ml) produced nothing. Benzene (100 ml) containing 10% ethanol y i e l d e d small needles which grew to large needles at 175° C and melted at 223 - 224° C (Material B-2). One hundred per cent ethanol (100 ml) produced c r y s t a l s melting at 175 - 185° C (material B-3). Compound C (3-phenylphthalmidine) was reduced using the same experimental conditions. Chromatography of the re a c t i o n product gave 63 three fractions of melting point; 125 - 150° C (C-l), 169 - 170° C (C-2) and 223 - 224° C (C-3),. These materials were also obtained from a parallel reduction of 3-phenylphthalimidine prepared by the method of Rose (39). Material B-2 and C-3 were shown to be identical by com parison of infrared spectrum and mixed melting point. The infrared spectrum of compound C-3 i n potassium bromide disc showed the following major absorptions; 3210S, 2920S, 2830S, 1673S, 1440M (broad), 1383W, 1347W, 1325W, 1275M, 1255M, 1195W, 1172W, 1142W, 982W, 888W, 862W, 752M, 717W. The spectrum of 3-phenylphthalimidine compared to i t s re duced product i s shown on page 64. Detailed comparison of the spectra of C-3 was made with that of 3-phenylphthalimidine. Bands present i n 3-phenylphthalimidine at 1458 cm"1, 1472 cm"1, 1497 cm"1, 1599 cm"1 and 1608 cm * were not present i n the reduced product. The 3-phenylphthalmi- dine band at 3020 cm"1 associated with aromatic C-H i s not present i n the reduced product. The bands i n the 700 cm*1 region associated with ring substitution also are not found i n C-3. The 2830 cm"1 vibration associated with tertiary CH i s stronger i n the reduced product than i n 3-phenylphthalimidine. The lactam carbonyl (1677 cm"1) of 3-phenylphthalimidine appears i n the reduced product with a slight change i n frequency (1673 cm"1). A l l of these observations are con sistent with the reduction of both benzene rings to produce 3-cyclohexyl hexahydro-phthalimidine. W/we N U M B E R S AV* C V \ ~ X This conclusion i s supported by an a l y s i s of C-3. Calculated f o r C, 76.02; H, 10. 41; N, 6.33; m.w. 221 C u H 2 3 N 0 i Found: C, 76.17; H, 10.37; H, 6.15; m.w. 216 d. Repeat of r e a c t i o n of benzophenone oxime Benzophenone oxime was reacted with carbon monoxide under the same general conditions as on page 40. I n i t i a l pressure of carbon monoxide was 2250 p . s . i . at 18° C (2105 p . s . i . at 0° C). Benzophenone oxime (19.5 gm) (0.1 mole) was di s s o l v e d i n 30 ml of c a t a l y s t s o l u t i o n (0.02 mole) and the t o t a l volume brought to 60 ml with benzene. D e t a i l s of pressure readings were pl o t t e d , and are graphed on page 66. The o v e r a l l pressure drop was 1.77 moles per mole of substrate, c a l c u l a t e d as carbon monoxide. The material from the bomb was heated f o r 30 minutes at the temperature of r e f l u x i n g benzene. Benzene was evaporated to leave brown c r y s t a l l i n e material. This material was extracted with hot chloroform and an in s o l u b l e residue f i l t e r e d o f f (material I ) . Evapo r a t i o n of the chloroform y i e l d e d a dark brown material which formed a dark brown s o l u t i o n i n methanol and l e f t a dark red residue (material I I ) . -2. 20 AO 60 TIMS. 80 \00 \20 140 ON 67 M a t e r i a l II turned green on drying and f a i l e d to melt at 350° C. I t l e f t a black residue on i g n i t i o n which tested f o r cobalt. White c r y s t a l s (7 gm) c r y s t a l l i z e d from the methanol (m.p. 180 - 210° C) (material I I I ) . Extensive t r i a l s of r e c r y s t a l l i z a t i o n from organic solvents f a i l e d to produce a pure compound corresponding to compound B of section I. Pure compound C could be obtained by repeated r e c r y s t a l l i z a t i o n s from benzene or methanol. From the methanol mother l i q u o r , containing c a t a l y s t decomposition products, i t was possible to i s o l a t e 6 gm of organic material making the t o t a l y i e l d 13 gm. Ah ether e x t r a c t was made of material I I I . The r e s u l t i n g c r y s t a l s (1 gm) melted at 194 - 200° C. These were r e c r y s t a l l i z e d from ether and 3 separate crops were obtained. The f i r s t (100 mgm) melted 220 - 230° C; the second (200 mgm) 170 - 195° C; and the t h i r d (100 mgm) 220 - 230° C. The middle crop (200 mgms) was dissolv e d i n 3 ml of benzene placed on an alumina column ( 3 ^ cm x 8 cm) and eluted with benzene with the fo l l o w i n g r e s u l t s ; the f i r s t 250 ml of benzene pro duced nothing; the next 200 ml produced, a f t e r r e c r y s t a l l i z a t i o n , 120 mgm of compound B (m.p. 197 - 199° C). The i n f r a r e d spectrum of t h i s material showed the f o l l o w i n g major absorptions (potassium bromide d i s c ) ; 3420(broad)S, 2885W, 1704M, 1690W, 1627M, 1535M, H99W, 1A75W, 1463W, 1366W, 1346W, 1329W, 11A0M, 1086M, 774W, 765W, 753W, 741W, 731W, 700M. The spectrum i s reproduced on page 47. 68 A f u r t h e r 100 ml of benzene produced nothing. Benzene ethanol 50:50 (100 ml) produced 3-phenylphthalimidine. The f i r s t and t h i r d crops were now chromatographed and both yi e l d e d only traces q u a n t i t i e s of compound B. They consisted almost wholly of 3-phenylphthalimidine. Compound B f a i l e d to react with co l d aqueous or a l c o h o l i c potassium permanganate. I t f a i l e d to react with bromine i n water or carbon t e t r a c h l o r i d e . No reaction was v i s i b l e with hydrochloric or formic acids. A red c o l o r could be detected by pouring concentrated sulphuric a c i d onto dry c r y s t a l s which would subsequently d i s s o l v e to a pale green s o l u t i o n . A h y d r o l y s i s was attempted using the f o l l o w i n g conditions. Twenty mgm of compound B and 8 gm of potassium hydroxide were d i s  solved i n 30 ml of ethanol and 20 ml of water. Compound B was i n s o l u b l e i n the co l d mixture but d i s s o l v e d at r e f l u x temperature. Reflux was c a r r i e d out f o r 30 hours. The solvent was evaporated under reduced pressure, and allowed to c r y s t a l l i z e at 0° C. C r y s t a l s recovered were shown i d e n t i c a l with compound B by mixed melting point. Twenty mgm of compound B were heated on the steam bath f o r one-half hour with concentrated sulphuric acid. The r e a c t i o n mixture was poured i n t o c o l d water and c r y s t a l s recovered proved i d e n t i c a l to compound B. 69 3-Phenyloxindole was prepared by the method of Meisenheimer (28) f o r comparison with compound B, because of s i m i l a r i t y i n analysis, s o l u b i l i t i e s and chemical properties,, Mixed melting point produced a marked depression. A re-analysis of compound B produced the following r e s u l t s : Calculated f o r G, 79.80; H, 5.42; N, 6.90; Mol. wt. 406 G 2 7 H 2 2 N 2 ° 2 J Found: C, 79.44; H, 5.28; N, 6.86; Mol. wt. 379 e. Reaction of benzophenone oxime i n the presence of small amount of d i c o b a l t octacarbonyl Reaction between benzophenone oxime and carbon monoxide was c a r r i e d out i n the presence of a small amount of d i c o b a l t octacarbonyl i n the following manner. A f t e r preparation of the c a t a l y s t most o f the c a t a l y s t s o l u t i o n was poured o f f l e a v i n g the unreacted residue of cobaltous carbonate with approximately 2 ml (0.002 mole) of c a t a l y s t s o l u t i o n . A s o l u t i o n of 16 gm (0.088 mole) of benzophenone oxime i n benzene was added to t h i s residue and the t o t a l volume made exactly 50 ml with benzene. On reaching 200° C i t was apparent that the reaction was not proceeding as described i n section I I I . The r e a c t i o n vessel was allowed to cool and reheated twice on the assumption the reaction might be proceeding slowly. T o t a l heating time was four hours. The benzene was evaporated o f f and the product was digested i n chloroform to obtain a brown f i l t r a t e and a pink residue. This 70) residue contained no organic material, but d i d contain cobalt and appeared i d e n t i c a l i n appearance with cobaltous carbonate. On evapo r a t i o n o f the brown chloroform s o l u t i o n a brown o i l was obtained as product (10.5 gm). The brown o i l was d i s s o l v e d i n ether and cooled at 0° C. C r y s t a l s were obtained and r e c r y s t a l l i z e d from methanol, to y i e l d 90 mgm of 3-phenylphthalimidine. The brown o i l was soluble i n alcohols, acetone, ether, benzene, chloroform, or carbon t e t r a  c h l o r i d e . I t was stable to the action of hot concentrated hydrochloric a c i d or hot concentrated sodium hydroxide. I t was i n s o l u b l e i n water, hydrochloric acid or sodium hydroxide. Concentrated sulphuric a c i d produced a green s o l u t i o n . On d i l u t i o n a c o l o r l e s s c o l l o i d a l suspension was obtained which would not d i s s o l v e on b a s i f y i n g with sodium hydroxide. The o i l b o i l e d at 290° C (uncorrected) 305 - 307° C (cor rected). I t d i s t i l l e d without decomposition at atmospheric pressure. Reaction with hydroxylamine hydrochloride i n aqueous ethanol y i e l d e d white c r y s t a l s (m.p. 144- - 145° C). Reaction with 2-4-dinitrophenyl- hydrazine y i e l d e d yellow c r y s t a l s (m.p. 245 - 247° C). The l i t e r a t u r e values f o r benzophenone oxime and benzophenone, 2-4-dinitrophenylhydrazone o o are 144 C and 247 C. The l i t e r a t u r e b o i l i n g point f o r benzophenone i s 306° C. These observations i d e n t i f y the major r e a c t i o n component as benzophenone. The residue from the d i s t i l l a t i o n of the brown o i l was r e  c r y s t a l l i z e d from a water-ethanol mixture (m.p. 144 - 145° C). Mixed 71 melting point with an authentic sample of benzophenone oxime was 144 - 145° C. The residue reacted with bromine i n carbon t e t r a c h l o r i d e without evolution of hydrogen bromide. C r y s t a l s produced melted at 223 - 224° C. D. Reaction of 0-methyl Ether of Benzophenone Oxime i n the Presence of Di c o b a l t Octacarbonyl a. Preparation of the 0-methyl ether of benzophenone oxime Benzophenone (20 gm) (0.11 mole) and 0-methyl hydroxylamine hydrochloride (14 gm) (0.195 mole) were refluxed f o r 4 hours with 20 ml of pyridine and 200 ml of ethanol. The ethanol was then removed under reduced pressure. Slow addition of water with s t i r r i n g produced c r y s t a l s . These were r e c r y s t a l l i z e d twice i n the f o l l o w i n g manner. The c r y s t a l s were di s s o l v e d i n minimum quantity of acetone and an equal quantity of methanol was added. Water was added t i l l the cloud point was reached. C r y s t a l l i z a t i o n was allowed to proceed at 0° C. The y i e l d was 20.0 gm (0.095 mole) (87$ of t h e o r e t i c a l ) . This recrys t a l l i z a t i o n procedure was taken from Hauser and Hoffenberg (20). b. Reaction procedure The carbonylation r e a c t i o n was c a r r i e d out e s s e n t i a l l y as i n previous sections. An amount of 10.5 gm (0.05 mole) of 0-methyl ether 72 of benzophenone oxime and 35 ml (0.026 mole) of c a t a l y s t l i q u o r were used. The t o t a l volume of r e a c t i o n so l u t i o n was 50 ml. The thermo s t a t was o r i g i n a l l y set at 180° C. No r e a c t i o n was apparent at t h i s temperature so the temperature was r a i s e d i n 10 degree steps to 220° C maintaining the temperature f o r 6 or 7 minutes at each l e v e l . Heating was continued at 220° C f o r 71 minutes; a f t e r c o o l i n g the o v e r a l l pressure drop was 120 p . s . i . measured at 0° C. This represents 0.065 mole of carbon monoxide or 1.3 moles per mole of substrate. A d e t a i l e d p l o t of pressure versus time at constant temperature I s shown on page 73. c. Separation and i d e n t i f i c a t i o n of products The product was a homogeneous benzene so l u t i o n . The benzene was removed under reduced pressure to produce a yellow d i s t i l l a t e from which a very few orange c r y s t a l s separated which had the appearance of d i c o b a l t octacarbonyl. The residue was a dark t a r r y material. This material was sludged with co l d chloroform to produce 50 ml of a brown chloroform s o l u t i o n and a residue which contained organic material and cobalt. Seven ml of t h i s s o l u t i o n were evaporated and d i s s o l v e d i n benzene then placed on a column ( 5 0 $ alumina and 50$ c e l i t e ) (3 cm diameter x 6 cm) f o r chromatography. The f i r s t 100 ml of benzene eluent produced a brown o i l which on warming i n l i g h t petroleum ether became insolub l e i n petroleum ether or benzene. This material f a i l e d to melt and gave a p o s i t i v e t e s t f o r cobalt. Further e l u t i o n with benzene pro duced nothing. E l u t i o n with ethanol produced a s i m i l a r o i l which also T O T / \ U ^ C A C T V O V A P R E S 5 U « t C o ^ l C T E O T o 0 ° C Vb«. 0 - W \ ^ T V \ > < \ _ ^L"\ V\<c^«. O I F 0.0% \V\0W« CKTrW-^ST IP 0- •i w V ti a- 2\oo ZOOO _ T E M P E R A T U R E . \N + 20 40 6O 8 O \0O T I M E \ M W W U T E S 0 0 ui a u K lit iii V v <*» \t% in v> is. V*) n contained cobalt. M a t e r i a l (20 mgm) c r y s t a l l i z e d from the ethanol s o l u t i o n of m.p. 220 - 222° C. The residue from the chloroform ex t r a c t i o n was treated with co l d benzene. A" blue s o l u t i o n was obtained and a v i o l e t residue. On evaporation of the s o l u t i o n white c r y s t a l s covered with a deep blue o i l y material resulted. Cold acetone d i s s o l v e d the blue c o l o r completely l e a v i n g some white c r y s t a l s . The acetone was evaporated to leave a blue o i l y m ateriel which burned b r i g h t l y on an i g n i t i o n t e s t l e a v i n g a black residue. The residue contained cobalt. The i n f r a r e d spectrum of t h i s material f a i l e d to show a high frequency absorption which could be associated with the carbonyl s t r e t c h i n g frequency of a cobalt carbonyl compound.. This o i l was soluble i n organic solvents (acetone, benzene, chloroform, alcohols) and soluble without effervescence i n concentrated hydrochloric acid. An acetone s o l u t i o n of the o i l was allowed to c r y s t a l l i z e at 0° C., The c r y s t a l s which were produced melted at 217 - 222° C. These were shown i d e n t i c a l to 3-phenylphthalimidine a f t e r r e c r y s t a l l i z a t i o n . The residue from the c o l d benzene extr a c t was now treated with hot chloroform to give a green s o l u t i o n and a v i o l e t residue. The residue seemed to contain no organic material but d i d contain cobalt. The above chloroform and benzene solutions were evaporated to y i e l d 7 gm of l i g h t brown organic material m.p. 200 - 217° C. A warm benzene extraction d i s s o l v e d 2.7 gm l e a v i n g a residue of 4.3 gm. A 10$ a l i q u o t of the benzene sol u t i o n was chromatographed on an alumina column (9 cm x 3 cm). The column retained a narrow brown band at the top and pro duct appeared very slowly on benzene e l u t i o n . Each f r a c t i o n c o l l e c t e d 75 melted i n the range 210 - 217° C. These f r a c t i o n s were combined and r e c r y s t a l l i z e d from methanol and benzene. Their m.p. was 222 - 224° C, a f t e r r e c r y s t a l l i z a t i o n . Mixed m.p. and preparation of acetate d e r i v a t i v e (m.p. 153 - 154° C) proved t h i s compound to be 3-phenylphthalimidine. A t o t a l of 0.25 gm was recovered from the column. Ethanol e l u t i o n produced 150 mgm of a component m.p. 210 - 250° G (material V). The column was then washed with 500 ml of acetone. A l i g h t brown f l u i d (7 gm) was obtained which was obviously not a product of the o r i g i n a l r e a c t i o n . This f l u i d reacted instantaneously with i c e c o l d 2% aqueous potassium permanganate and with bromine i n carbon t e t r a c h l o r i d e . The b o i l i n g point of t h i s material was 163 - 166° C (corrected). L i t e r a t u r e f o r di-acetone alcohol i s 164 - 166° C. A l l solvents which had been used were evaporated down to t r y to reproduce t h i s l i q u i d without success. M a t e r i a l V (150 mgm) (the high melting f r a c t i o n ) was now rechromatographed. Benzene e l u t i o n produced 140 mgm melting 219 - 222° C. Alcohol e l u t i o n produced 1 mgm of material melting 218 - 300° C. This l a s t 1 mgm i s apparently the only organic compound present which i s not 3-phenylphthalimidine. 76 IV. BIBLIOGRAPHY Aldridge, C. L., Posce, E. V. and Jonassen, H. B.; J . Phys. Chem. &>, 869 (1958). Beckmann, E. j Ber. 23., 1685 (1890). Bengelsdorf, I. S.j J . Am. Chem. Soc. 80, 1442 (1958). B i l l e t e r , 0. G.; Ber. 36, 3219 (1903). B i l t z , H. j Ber. _)» 2635 (1907). Buckley, G. D. and Ray, N. H.j J . Chem. Soc. 1151 (1949). Coe, C. S. and Doumani, T. F. j J . Am. Chem. Soc. JO, 1516 (1948). Davis, T. L. and Blanchard, K. C.j J . Am. Chem. Soc. 45. 1819, (1923). Donahue, J . j J . Am. Chem. Soc. 7_, 4172 (1956). Eidus, Y. T. and Izmailov, R. I.; Chem. Abst. 5_» 3431 (1957). Eidus, Y. T. and Izmailov, R. I . j Chem. Abst. 5_, 18130 (1957). 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