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Reaction of Triphenylbenzoylmethylenephosphoranewith Benzoyl Peroxide DONALD B. DENNEY’ A N D THOMAS M. VALEGA~ The School of Chemistry, Rutgers, The State University, New Brunswick, New Jersey Received Ju2y 1 , 1963 Triphenylbenzoylmethylenephosphorane reacts with benzoyl peroxide at room temperature to give triphenylphosphine oxide and a mixture of benzoic anhydride and benzoic benzoylmandelic anhydride. The formation of these products is rationalized mechanistically.
Several recent papers have described the reactions of phosphoranes with various oxidizing agents. It was the purpose of the work now being reported to study the reactions of phosphoranes with benzoyl peroxide. Tripheny lbenzoylmet hy lenephosphorane (I)
was taken as a representative of the more stable resonance stabilized phosphoranes. It was found that I reacts readily with benzoyl peroxide a t room temperature in solvents such as carbon tetrachloride and chloroform. By a combination of analytical methods it was demonstrated that 2 moles of peroxide were required to consume 1 mole of phosphorane. The infrared spectra of several reaction mixtures had carbonyl bands which indicated that an ester as well as anhydrides had been formed. For example the infrared spectra of reaction mixtures in ethanol-free chloroform exhibited bands a t 5.50, 5.55, 5.65, and 5.80 p . Although the presence of these peaks does not prove that anhydrides and an ester were formed, their positions are in agreement with this p o ~ t u l a t e . ~The formation of triphenylphosphine oxide also was indicated. The reaction mixture from a reaction conducted in pure chloroform was treated with an aqueous solution of sodium bicarbonate and triethylamine. The basic hydrolysate yielded a mixture of acids on acidification. Spectral evidence, infrared and n.m.r., as well as evidence from other experiments to be cited indicated that this was a mixture of benzoic and benzoylmandelic acid. The nonhydrolyzed neutral material was found to be triphenylphosphine oxide contaminated with N,Ndiethylben~amide.~ When the reaction was conducted in commercial chloroform, i.e., containing ca. 1% ethanol, and its course was followed by periodic inspection in the n.m.r., it was easily seen that some substance was being formed which was reacting with the ethanol.
From such a reaction mixture there was isolated, after hydrolysis with sodium bicarbonate and triethylamine, ethyl benzoylmandelate. Another major product was triphenylphosphine oxide. From the basic extracts there was isolated a mixture of acids, whose spectral characteristics indicated benzoic and benzoylmandelic acids. Periodic examination of the n.m.r. spectrum of a reaction mixture in pure chloroform showed that initially a peak a t r 3.60 appears and reaches a maximum but then diminishes in intensity and a new peak a t T 3.75 appears. On standing 7 days there was no further change in intensity or position of these peaks. The ‘z 3.60 peak was always considerably more intense than the r 3.75 peak. On the basis of the infrared data, the n.m.r. data, and the formation of ethyl benzoylmandelate, it seemed reasonable to suggest that the products of the reaction were benzoic anhydride and benzoic benzoylmandelic anhydride. In order to test this hypothesis mandelic acid was treated with benzoyl chloride in pyridine. This should lead to the initial formation of benzoic benzoylmandelic anhydride. The material obtained after a standard purification sequence had in the n.m.r. two general absorptions for aromatic protons and also peaks a t T 3.70 and 3.88 (carbon tetrachloride solvent). The r 3.70 peak was by far the most intense of the two. After standing 1 year, the sample had solidified and the n.m.r. was investigated again. The r 3.70 peak had disappeared and the r 3.88 peak had grown much larger. A reaction conducted in carbon tetrachloride also had peaks a t r 3.70 and 3.88; the former being the most intense. The infrared spectra of the reaction mixture and the synthetic material were very similar in the carbonyl region. It was obvious though that the synthetic mixture contained much less benzoic anhydride. The band a t 5.55 /1 was considerably less intense than that of the reaction mixture. The 5.8-p band was quite intense but this is undoubtedly due to the contribution of the ester carbonyl. Although it was not possible to isolate the primary products from this reaction and it was necessary to resort to a second chemical reaction before isolation, the data point strongly to the equation illustrated. The 3.60 (chloroform) and 3.75 (carbon tetrachloride) peaks are assigned to the benzylic hydrogen of 11.
(1) Rutgers Research Council Faculty Fellow, 1963-1964. (2) National Defense Education .4ct Fellow, 1959-1962; Public Health Service Fellow, 1962-1963. (3) (a) D. R . Denney. L. C. Smith, J. Song, C. J. Rossi, and C. D. Hall, J . Org. Chem., 48, 778 (1963); (b) D. B. Denney and S. T.Ross, ibid.. 8’7, 998 (1962); (c) G. Maerkl, Ber., 91, 3003 (1962); (d) F. Ramires, R. B . Mitra, and N. R . Desai, J . A m . Chem. Soc.. 84, 5763 (1960). (4) L. J. Bellamy [“The Infrared Spectra of Complex Molecules,” 2nd Ed.,‘ John Wiley and Sone, New York, N. Y., 1958, Chap. 81 reports 5.59 and 5.79 for benzoic anhydride and c a . 5.50 and 5.72 p for aliphatic and mixed aliphatic aromatic anhydrides. Benzoates (Chap. 11) absorb a t ea. 5.80p .
( 5 ) Several reaction mixtures were hydrolyzed b y this technique. Invariably small amounts of N,N-diethylbenzamide were found in the neutral products. Initially i t was thought t h a t diethylamine, present a s a contaminant in the triethylamine, was reacting with benzoic anhydride t o give the amide. When triethylamine which was absolutely free of diethylamine was used, N.N-diethylbenzamide was still formed. A most likely explanation for this behavior is t h a t small amounts of benzoyl peroxide present in the reaction mixture react with triethylamine t o give diethylamine. This is a well-known reaction: see, for example, A . G. Davies, “Organic Peroxides,” Butterworth and Co., London, England, 1961, pp. 13.5-136. T h e diethylamine then reacts with benzoic anhydride t o give the amide.
0
II
(c~.H~)ap=CH-c-cgHg
I (CsHs)aPa
0
+ 2(C& 0
I1
e
-0)2
--f
0
0
II
/I + (CeHaC)zO +CsH5C-O-C-CH-C6Hs 11
b-C--C&
I1
0
FEBRUARY, 1964
TRIPHEXYLBENZOYLMETHYLENEPHOSPHORANE WITH BENZOYL PEROXIDE
Ethanolysis or hydrolysis by adventitious water gives rise to the T 3.75 (chloroform) and 3.88 (carbon tetrachloride) peaks which are assigned to benzoylmandelic acid.6 The concordance between the n.m.r. spectra of the synthetic material and that of the reaction mixture strongly supports this postulate. The formation of ethyl benzoylmandelate when ethanol is present in the reaction mixture is in complete accord with the formation of 11. The mixed anhydride would be expected to react preferentially a t the aliphatic carbonyl carbon atom and also it would react more rapidly than benzoic anhydride.I It should be noted that the n.m.r. spectrum of a reaction mixture run in chloroform containing ethanol did indicate that a small amount of ethyl benzoate was formed. The nature of the reaction products, the relatively low temperatures required to effect the reaction, and the lack of attack on solvent suggest that the reaction is ionic in nature. In order to establish whether the reaction proceeds by an ionic or radical path it was conducted in the presence of three well-known inhibitors: galvinoxyl,s trans-stilbene, and 2,6-di-t-butyl-4methylphenol.lO The course of the rea.ctions were observed by comparing infrared spectra with those obtained from a reaction mixture which did not contain an inhibitor. In no case was there any noticeable effect on the course or rate of the reaction. It was noted that the galvinoxyl was destroyed (loss of color). This could well be due to its reaction with intermediates formed during the reaction, since it is quite a reactive substance.s The results of the experiments in the presence of inhibitors indicate that the reaction does not follow a radical path although there may be some radicals formed by side reactions. The formation of the products can be rationalized by the mechanism in col 2. It is suggested that the phosphorane acts as a nucleophile and displaces on one of the peroxidic oxygens to give the ion pair (111). Nucleophilic displacements of this type are wellknown.” Addition of benzoate ion to the carbonyl carbon to give IV followed by displacement of triphenylphosphine leads to V. The reaction of triphenylphosphine with benzoyl peroxide to give benzoic anhydride and triphenylphosphine oxide is well-known. l 2 The sequence from I11 to V is reasonable and is supported by the observations that nucleophiles often add to the carbonyl carbon atom of a-halo ketones to give an intermediate alkoxide ion which displaces halide to yield a substituted epoxide similar to V.I3 Rearrangement of the epoxide leads directly to the mixed anhydride (11). The epoxide (V) should be (6) I n view of the isolation and structure proof of ethyl benaoylmandelate. i t did not seem necessary t o characterize more fully the mixture of acids obtained on hydrolysis. These all had the T 3.75 (chloroform) and 3.88 (carbon tetrachloride) peaks. (7) (a) P. S. Bailey and Y. G. Chang [J.Org. Chem., 47, 1192 (1962)l have shown t h a t benzoic acetic anhydride reacts with ethanol to give 85% attack a t the acetic carbonyl; (b) C. A. Bunton and S. G. Perry, J. Chem. Soc.. 3070 (1960). ( 8 ) F. D. Greene, W. Adam. and J. E. Cantrill, J. A m . Chem. Soc., 83, 3461 (1961). (9) C. G . Swain. W. H. Stockmayer, and J. T. Clarke, ibid., 74, 5426 (1950). (10) K. U. Ingold, Chem. Rec., 61, 577 (1961). (1 1 ) A. G . Davies, “Organic Perbxides,” Butterworths and Co., London, England, 1961,Chap. Y. (12) L. Horner and W. Jurgeleit, Ann., 691, 138 (1955). (13)(a) T.I. Temnikova and N. I. Almashi. Zh. Obahch. K h i m . , 43, 1338 (1953); Chem. Abslr., 48, 12025 (1954); (b) R. Justoni. Garr. chim. ital., 69,378 (1939).
0
311
441
1
particularly susceptible to rearrangement because development of a partial positive charge on either carbon of the epoxide ring is enhanced by the benzoyloxy and phenyl groups. It is interesting to note that the same product is obtained irrespective of whether phenyl or hydrogen migrates. Other mechanisms can be written for the reaction; in particular, several ways can be devised for proceeding from I11 to 11. It also is interesting to note that other phosphoranes will probably react with benzoyl peroxide to give intermediates similar to 111. There seems to be no reason for predicting that the following reactions should be similar.
Experimental14 Benzoylmethylenetriphenylphosphorane (I).-The modified procedure of Ramirez and Dershowitzl6 gave yields of ca. 75y0, m.p. 185-187”, lit.lSbm.p. 186-188’. Stoichiometry of the Reaction.-To a solution of 7.6 g. (0.02 mole) of I in 60 ml. of chloroform was added with stirring over 45 min. 4.84 g. (0.02 mole) of benzoyl peroxide in 40 ml. of chloroform. Titration of an aliquot for phosphoranel6 concentration and another for peroxide’’ concentration showed that all of the peroxide had reacted and cu. 50% of the phosphorane had reacted. Additional incrementa of benzoyl peroxide were added until a total of 2 moles of peroxide per mole of phosphorane had been added. At this point there was no phosphorane left and only a small amount of benzoyl peroxide was present. Reaction of I with Benzoyl Peroxide in Stock Chloroform.Benzoyl peroxide (43.7 g., 0.181 mole) in 300 ml. of chloroform waa added with stirring to 34.3 g. (0.0903 mole) of I in 200 ml. of chloroform. A portion of the reaction mixture, 425 ml., was extracted with 400 ml. of 5% sodium bicarbonate solution. Acidification gave a solid which was taken up in ether. Evaporation of the dried (magnesium sulfate) ether solution gave 13.4 g. of material. The infrared spectrum of this material had typical (14) Analyses were performed by G . Robertson, Florham Park, N. J . Melting points are corrected. N.m.r. spectra were obtained with a Varian A-60 spectrometer; r-values are relative to tetramethylsilane a s internal standard. G.1.p.c. analyses were conducted with a n F & M Model 500 chromatograph using the conditions specified. (15) (a) F. Ramires and S. Dershowita, J . Org. Chem., 42, 41 (1957); (b) D . B. Denney and S. T . Ross, ibid., 47, 998 (1962). (16) 8. T.Rossand D. R . Denney, Anal. Chem., 32, 1896 (1960). (17) L. S. Silbert and D. Swern, ibid., 30, 385 (1958).
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DENNEY AND VALEGA
acid absorption and two carbonyl peaks a t 5.83 and 5.93 p. The n.m.r. spectrum in trifluoroacetic acid had a peak at T 3.70 and two sets of complex multiplets centered a t ca. r 1.96 and 2.52. The n.m.r. spectrum in chloroform had aromatic absorptions and a peak at T 3.76 and in carbon tetrachloride this absorption was found a t r 3.85. The extracted chloroform solution was stirred at room temperature for 45 hr. with a mixture of 350 ml. of 57& sodium bicarbonate solution and 50 ml. of triethylamine. Acidification of the bicarbonate extract yielded 18 g. of material whose infrared spectrum was identical with that of benzoic acid. The chloroform solution was extracted with four 300-ml. portions of 5% hydrochloric acid, 300 ml. of 5% sodium bicarbonate solution, 450 ml. of water, and then dried with magnesium sulfate. Removal of the solvent afforded an oil which was triturated with ether to give 19.6 g. of triphenylphosphine oxide, which gave no depression of melting point with an authentic sample. The infrared spectrum of this material was identical with that of an authentic sample. Evaporation of the ether triturant gave 19.7 g. of oil which was molecularly distilled. -4 number of fractions were collected. Two major fractions, 2.3 g. and 3.7 g., b.p. 100-122" (block) at 0.01 mm., were analyzed by g.1.p.c. on a 2-ft. silicone gum rubber column, programmed from 100-350" at 15"/min. The first fraction had two major components with retention times of 4.6 and 7.9 min. A sample of the 4.6-min. component was collected and shown to be N,N-diethylbenzamide. Its infrared spectrum and g.1.p.c. retention time were identical with that of an authentic sample. The second fraction showed one major component, retention time 8.0 min. A sample of this material was collected. Its n.m.r. and infrared spectra were identical with that of an authentic sample of ethyl benzoylmandelate. The total distillate, 14.4 g., consisted of these two components with ethyl benzoylmandelate constituting by far the major amount. Ethyl Benzoylmandelate .'*-This compound was prepared by acid-catalyzed esterification with ethanol followed by benzoylation with benzoyl chloride in pyridine. The infrared spectrum had two carbonyl bands at 5.7 and 5.8 j i . The n.m.r. spectrum in carbon tetrachloride had two multiplets of aromatic protons centered a t T 2.0 and 2.6, benzylic proton at T 3.97, quartet of methylene protons a t T 5.82, and a triplet (methyl) a t T 8.78. The integrated ratio was 2 : 8 : 1 : 2 : 3 . The n.m.r. spectrum in chloroform showed slight shifts, ca. T 0.03, of all peaks except for the benzylic proton which was found a t T 3.85. Reaction of I with Benzoyl Peroxide in Ethanol-Free Chloroform.-In this reaction the molar ratio of 2: 1 peroxide-phosphorane was used. The conditions and quantities were essentially as before. After the extraction with triethylamine and sodium bicarbonate solution, there was obtained 75% of mixed benzoic and benzoylmandelic acids. The neutral residue consisted of triphenylphosphine oxide, N,N-diethylbenzamide, and most probably some benzoic anhydride, since more benzoic acid was obtained on further extractions with bicarbonate solutions. Spectral Measurements on Reaction Mixtures.-A reaction mixture A in ethanol-free chloroform showed after 2 hr. two complex multiplets a t T 1.8 and 2.5 and a single peak at T 3.60. After 6 hr. a small peak appeared a t r 3.75; a t 25 hr. the peak a t T 3.60 had decreased in intensity and that a t T 3.75 had increased, although it was still less intense than the T 3.60 peak. Little further change was noted. The infrared spectrum showed carbonyl absorption a t 5.50, 5.55, 5.65, and 5.80 w . A similar reaction mixture B in ethanol containing chloroform after 2 hr. had T 1.8 and 2.5 complex multiplets and two single (18) G . M . Robinson and R. Robinson, J. Chem. Soc., 106, 1465 (1914).
VOL.29
peaks a t 7 3.58 and 3.85, also methylene and methyl protons. After 25 hr. the peak a t T 3.58 had decreased in intensity and a new peak appeared a t 7 3.75. The r 3.85 peak had increased in intensity. After 7 days the T 3.58 peak was gone. A small peak at T 3.75 remained. The T 3.85 peak had increased and was by far the major absorption in this region. Two quartets of methylene protons centered a t T 5.65 and 5.85 and two triplets of methyl protons a t r 8.67 and 8.85 were present. The n.m.r. spectrum of ethyl benzoate had a quartet a t r 5.65 and triplet a t T . 8.65 The other ethyl group agrees well with that of ethyl benzoylmandelate. A reaction mixture in carbon tetrachloride had after 20 hr. two sets of complex multiplets a t T 1.9 and 2.7 and two single peaks at T 3.68 and 3.90. The T 3.68 peak was considerably more intense than the T 3.90 peak. Reaction of Mandelic Acid and Benzoyl Chloride.-To a solution of 1.52 g . (0.01 mole) of mandelic acid and 1.58 g. (0.02 mole) of pyridine in 25 ml. of ethanol-free chloroform was added 2.82 g. (0.02 mole) of benzoyl chloride in 10 ml. of chloroform. After 30 min. the solution was extracted with 12 ml. of 1% hydrochloric acid, 20 ml. of 5y0 sodium bicarbonate solution, and 25 ml. of water. The dried (magnesium sulfate) solution was evaporated to give 3.30 g . of clear oil. The infrared spectrum had bands in the carbonyl region at 5.50, 5.60, 5.75 and 5.80 p . The n.m.r. spectrum in carbon tetrachloride had two sets of complex multiplets a t ca. r 1.9 and 2.6 and two single peaks a t 3.70, most intense, and 3.88. After standing 1 year the oil had solidified. The T 3.70 peak had disappeared and the T 3.88 peak had greatly increased in intensity. The bands at 5.50 and 5.60 p had disappeared and there remained one strong band a t 5.75 p with a shoulder a t 5.80 j i . Typical acid absorption in the 3-4-p region was present. Reaction of Benzoylmethylenetriphenylphosphorane with Benzoyl Peroxide in the Presence of Galvinoxy1.-A solution of 0.39 g. (0.001 mole) of I and 0.04 g. (0.0001 mole) of galvinoxyl in 10 ml. of stock chloroform a t room temperature showed no visible color change after standing 30 min. Benzoyl peroxide (0.49 g., 0.002 mole) was added. The infrared spectrum was taken five times over 1 hr. and a t the end of 2, 4, and 8 hr. Comparison with spectra taken on a solution of the same composition but without galvinoxyl showed them to be essentially identical. The deeply colored solution faded rapidly and after 100 min. it wm light yellow. N o further color change was noted. Reaction of Benzoylmethylenetriphen$4phosphorane with Benzoyl Peroxide in the Presence of trans-Stilbene.-.4 solution of the same composition as that described before except for the inclusion of 0.36 g. (0.002 mole) of trans-stilbene was subjected to periodic infrared examination. Comparison with the spectra of the control showed that the rate of disappearance of the benzoyl peroxide was the same in both cases. The characteristic 10.36p band of trans-stilbene did not alter in intensity. Reaction of Benzoylmethylenetriphenylphosphoranewith Benzoyl Peroxide in the Presence of 2,6-Di-t-butyl-4-methylphenol.A solution of the same composition as used above except for the addition of 0.08 g. (0.0004 mole) of 2,5-di-t-butyl-4-methylphenol wm subjected to periodic infrared examination. Comparison with the spectra of the control showed that the rate of disappearance of the benzoyl peroxide was the same in both rases. The characteristic 2.7-p band of the phenol did not diminish in intensity.
Acknowledgment.-Funds for the purchase of the n.m.r. spectrometer were provided in part by the National Science Foundation.
