Pertanika 8(1), 67 '-71 (1985)

Utility of Triphenylphosphine Dihalides in Organic Reactions: Esterification Using Triphenylphosphine Dibromide as the Dehydrating Agent

NORDIN LAJIS Chemistry Department, Faculty of Science and Environmental Studies Universiti Pertanian Malaysia, Serdang, Selangor, Malaysia.

Key words: Esterification;, dehydration; triphenylphosphine; triphenylphosphine dibromide; acids; alcohols.

ABSTRAK

Satu kaedah baru pengesteran telah dikaji menggunakan trifenilfosfina dibromida sebagai agen pendehidratan, Kajz'an ini telah menunjukkan bahawa kaedah ini adalah berguna bagi asid aromatik atau arilalilz'k. Kajian ini juga telah menunjukkan bahawa alkohol primer dan sekunder mengesterkan asid dengan memuaskan, sedangkan alkohol tertier tidak bertindakbalas.

ABSTRACT

A new esterification method was investigated using triphenylphosphz'ne dibromide as a dehydrating agent. This investigation has established that the method is useful when the acid is aromati~ or arylallylic. That primary and secondary alcohols esteTZfy acid satisfactorily whereas ter­ tiary alcoholsfail to react was also established in this experiment.

INTRODUCTION triphenylphosphine dibromide in such a reaction has never been mentioned. Since this reagent The methodology of ester synthesis has can be easily prepared from the reaction of tri­ always attracted the attention of organic phenylphosphine and bromine, its utilization in chemists due to the versatility of this functional this reaction procedure can be attractive alter­ group (see for examples, Arieta. et al., 1983; native to the conventional esterification Kurita et at., 1982; Sekine et al" 1981; Nakao et methods. In this paper we wish to report our at., 1981; Kitazume et at" 1980). Aside from its finding on the utility of the triphenylphosphine uses as the final product such as flavorant and reagent in the synthesis of esters. polymer materials. the functionality has been widely utilized as reaction intermediates and ~ ¢3PBr2 q protecting groups in organic synthesis (Hegedus RCOH + R OH ;) RCOR + ethanol were purified either by distillation or N.H. LAJIS

recrystallization (wherever appropriate) prior to Preparation ofMethyl Benzoate their use. All solvents were dried over sodium metal and distilled before use. Silica gel for In a similar manner, 0.7 g (5.7 mmol) of chromatography, Lot 35945 (M & B) and silica benzoic acid was esterified using methanol 1.0 gel, Type 60F 254 (Merck) were used for column ml (24.73 mmol) in the presence of triphenyl­ and TLC analysis respectively. The proton phosphine dibromide. Kugelrohr distillation nuclear magnetic resonance spectra were record­ gave 0.57 (4.16 mmol) of the ester. ed either on Bruker WP-80 or Varian EM-60 NMR (CDCI , ppm); 4.3 (3H, s), 7.4 (3H, m); 3 spectrometers. The chemical shifts were record­ IR (NaCl, neat; em -1) 3010,2990,1720,1610,1445, ed in 5 p.p.m. using tetramethylsilane (0.00 1280, 1025, 710. p.p.m.) as the internal standard. Infrared spectra were recorded on a Beckman Acculab Preparation ofIsopropyl Benzoate T.M. 3 spectrophotometer using 1601 cm- I band ofpolystyrene for calibrating each spectra. In a similar procedure 0.7 g (5,7 mmol) of benzoic acid was react(:d with triphenylphos­ A generai reaction procedure in the prepa­ phine dibromide followed by the addition of 1.0 ration of esters using triphenylphosphine di­ ml (13.6 mmol) isopropyl a~cohol. After: kugel­ bromide as a dehydrating agent is represented in Tohr distillation, 0.65 g (3.99 mmol) of isopropyl the preparation of ethyl benzoate from benzoic benzoate was isolated. acid and ethanol below. The same amount of NMR (CDCI , ppm); 1.3 (6H, d,] = 7Hz), 5.15 triphenylphosphine dibromide as in this pre­ 3 (lH, m,] = 7Hz); 7.35 (3H, d - d,] = 6H, 2Hz); paration was used for all reactions. 7.95 (2H, m,j = 6Hz, 2Hz); IR (NaCl, neat; em -I): 3100, 3010, 2985, 1730, 1610, Preparation ofEthyl Benzaotefrom Benzoic 1450, 1280, 1030, 980, 775. Acid and Ethanol Preparation ofEthyl Cinnamate In a 100 ml three-necked round bottom flask, 2.88 g (11.0 mmol) of triphenylphospine The general procedure was followed in this was dissolved in 50 ml petroleum ether (b.p. reaction using 1.18 g (8.0 mmol) of cinnamic 40°C - 60°C). To it, was added 0.6'ml bromine acid and ethanol 1.15 ml (25.70 mmol) in the dropwise while stirring. A yellow precipitate of presence of triphenylphosphine dibromide. triphenylphosphine dibromide was formed and Upon work up and distillation, 1.01 g (5.76 the stirring was continued for five minutes. The mmol) ofmethyl cinnaIll~te was isolated. flask was cooled to O°C and 3.2 ml triethylamine NMR (CDCI , ppm) 1.2 (3H, t,] = 7Hz),4.2 was added. After stirring for another 5 minutes, 3 4.2 (2H, t,] 7Hz), 6.3 (lH, d,] 14Hz), a solution of 0.7 g (5.7 mmol) ~f benzoic acid in = = 7.3 (5H, br-m), 7.5 (lH, d,] = 14Hz). the minimum amount of petroleum ether was IR(NaCl, neat, em -I); 3100, 3010,1730,1610. added, followed by the addition of 2.5 ml (42:8 mmol) ethanol. The reaction was allowed to Preparation ofIsopropyl Cinnamate warm up to room temperature and the stirring continued overnight (20 hours). The reaction Similarly, 1.18 g (8.0 mmol) of cinnamic mixture was then filtered and the filtrate washed acid was esterified using 1.5 ml (19.60 mmol) of with aqueous 10% HCI followed by an aqueous isopropyl alcohol. Upon work up followed by 10% NaHCO 3 solution. The organic layer was distillation, 1.02 g (5.36 mmol) of isopropyl concentrated and distilled. The liquid collected cinnamate was collected. between 40°C - 50°C at 1.5 mm Hg on kugel­ NMR (CDCI , ppm); 1.3 (6H, d,]= 7Hz), rohr distillation was identified as ethyl benzoate. 3 5.15 (lH, m,] = 7Hz), 6.3 (lH, d,] = 14Hz) NMR (CCI , ppm); 1.3 (3H, t, 7Hz), 4.3 4 J = 7.3 (5H, br-m), 7.5(lH, d,] = 14Hz); (2H, q, J = 6Hz); 7.3 (3H, br- m); 8.0 (2H, IR (NaCl, neat, em -1) 3100,3010, 1730, 1650, d-d, J = 2Hz, 8Hz); IR (NaCI, neat, cm -I) 1630,1500,1450,1320,1300,1260,1180,1050, 3010,2980,1720,1605,1450,1280,1030,700. 980, 950, 775, 645.

68 PERTANlKA VOL. 8 NO. I, 1985 TRIPHENYLPHOSPHINE DIHALIDES AS THE DEHYDRATING AGENT IN ESTERIFICATION

Preparation ofOctyi Acetate present in large excess as compared to the acid. Comparably good results were obtained when Upon reacting 0.47 ml (8.0 mmol) of acetic methyl and isopropyl aicoh~l were used as acid with 1.26 ml (18.0 mmol) of octanol in the nucleophiles - see Table 1. Esterification of presen!=e of triphenylphosphine dibromide, 0.41 cinnamic acid with ethyl and isopropyl alcohol g (2.4 mol) of octyl acetate was isolated after gave satisfactory yields of the desired products. kulgelrohr distillation followed by column Extension of this procedure was attempted for choromatography (Silica gel/Chloroform). the preparation of tert-butyl esters. Reaction of benzoic acid with tert-butyl alcohol however fail­ NMR (CDC1 , ppm); 0.71-1.00 (3H, br), 3 1.00 - 2.00 (12H, br), 2.00 (3H, S), ed to produce the desired tert-butyl benzoate. A 4.10 (2H, t, J = 6Hz). similar result was true in the case of cinnamic IR (NaCl, neat, em -1); 2950, 2880, 1750, 1450, acid. This observation is not surprising since 1365, 1225, 1040. tert-butyl alcohol is too bulky to function as the suitable nucleophile in this reaction.

DISCUSSION AND RESULTS In order to establish the generality of this reaction, the esterification of saturated aliphatic Previous work haS' shown that triphenyl­ acids was carried out. The esterification of acetic phosphine dihalides react with carboxylic acids and hexanoic acids with either primary or to generate unstable acyloxyphosphonium salt secondary alcohol gave only poor yields (Table intermediates which can later decompose to acid 1). halides (Horner et ai., 1959; Regen and Lee, 1975). In this project, one could expect that if another nucleophile is present, its reaction with Furthermore, the reaction of hexanoic acid the acyloxyphoshonium salt should lead to the and benzyl alcohol gave benzyl chloride as the substitution product (Scheme I). major product with only a trace amount of benzyl hexanoate (on thin layer chromatography analysis, SiO /Chloroform). We examined this reaction using ethanol as the nucleophile. The reaction of triphenylphos­ o phine dibromide with benzoic acid followed by II CH (CH )4 COH + ct>3PBr2 + c/>CH 0H -----7 the addition of ethanol in the presence of tri­ 3 2 2 ethylamine produced ethyl benzoate. The yield was found to behest when the alcohol was II ct>CH2Br + CH3(CH2)4 COH° Scheme 1

o II RCOH + lBr 2

o II RCX + 3P = 0

PERTANIKA VOL. 8 NO. I, 1985 69 N.H. LAJIS

TABLE 1 Yields of esterification using triphenylphosphine dibromide

Acid Alcohol Ester (Yield %)

o-COOH CHpH ./0- CO 2CR~ (73)

o-COOH CHpHpH 0- C02CHPH~ (85) o-COOH (CH~2CH OH 0- COPH(CH~2 (70)

OCOOH (CH~POH not formed

CH = CH COOH CHpHpH ~ CH = CH CO CH CH (72) 0- o-_. 2 2 3 OH=CHCOOH (CH~PH OH 0- CH=CH C02CH(CH~2 (67) 0-CH=CH COOH (CH~POH not formed

CHpOOH CH~CH2)PH CHPOjCH)7CH3 (30)

CH~CH)FOOH CH~CHPH CH~CH)F02CHPH3 (27)

These observations suggest that the acyloxy­ nium salts, the attack on the carbonyl carbon by phosphonium salt intermediates undergo re­ alcohol is more predominant the acyloxyphos­ action with alcohols either by the attack on the phonium salts of aliphatic acids undergo acy­ carbonyl carbon to form esters or by displacing laxy-displacement reaction more predo~inant­ the acyloxy group from the phosphorus to form ly. This is not surprising since the carbo~yl an alkoxyphosphonium salt. A similar suggestion carbon of the benzoyl and cinnamoyl group are has been mentioned previously on the reaction of more susceptible to nucleophilic attack then the alcoh

Scheme 2

II cf> l Br2 + R oCOH ------;;. [ Br - + HBr o path a II r------".z. ROCR + cf> lO + HBr

Br- + - path b R~OH -[ .,PT rB, + R'OH R'Br + cf>lO

70 PERTANlKA VOL. 8 NO.1, 1985 TRIPHENYLPHOSPHINE DIHALIDES AS THE DEHYDRATlNG AGENT IN ESTERIFICATlON

CONCLUSION non-macrocydic precursor, J. Am. Chem. Soc. 97: 654. The esterification method using triphenyl phosphonium dibromide is useful for aromatic HASLAM, E. (1979): Activation and Protection of acids, with primary or secondary alcohols. The the carboxyl group, Chemistry and reaction can be an alternative preparation of Industry, 610 - 617. esters when the system needs a basic reaction HEGEDUS. L.S. and WADE. Jr. L.G. (1977): condition. Compendium of organic Synthetic Methods, ACKNOWLEDGEMENT Vol. III, John Wiley & Sons, New York, pp. 21- 23. The author wishes to thank Dr. Abd. Hamid HORNER. VON L., o EDIGER, H. and ROFF· Hadi for running the NMR spectra and Zainud­ MANN, H. (1959): Reaktionen mit triphenyl­ din and Muhammad for their assistance in the phosphine dihalogeniden" Ann. 626: 26. laboratory. KESHAVAMURTHY, K.S., V ANKAR, Y.P. and REFERENCES DHAR. D,N. (1982): Preparation of acid anhydrides, amides and esters using chIoro­ ApPEL, R. (1975): Tertiary phosphine/Tetra­ sulfonyl isocyanate as dehydrating agen, chloromethane, a versatile reagent for chlo­ Synthesis. 6: 506 - 508. rination, dehydration and P-N linkage, KITAZUME, T., and ISHIKAWA, H. (1980): Novel Angew. Chem., Intl. Ed. 14: 801. synthetic reactions using bis (2, 2,2-trifluo­ ARlETA. A.: CARCIA. T. and LAGO.J.M. (1983): roethoxy) diorganosulfurane., Bull. Chem. Reagent and synthetic methods 28. Modi­ Soc;Jap. 53(7): 2064. fied procedures for anhydride formation, KURITA. K. and IMAJO. H. (1982): Diphthali­ esterification and thioesterification of car­ mido carbonate: A new reagent for active boxylic acids by means of available phos­ ester synthesis.]. Org. Chern. 47(23): 4584. phorus reagents., Synth. Cornmun. 13(6): 471- 87. KURIHARA, T., NAKAJIMA Y., MITSUNOBU, O. (1976): Synethesis of lactone and Cydo­ BROWN. RF. (1975): Synthetic Polymers in alkanes. Cydization of w-hydroxyacids and Organic Chemistry, Wadsworth Publishing ethyl a -cyano-w-hydroxycarboxylate, Tet­ Co, Belmount, California, pp. 969 - 993. rahedron Lett., 2455. COREY. E.J. and BRUNELLE. J.D. (1976): New NAKAO,R., OKA.K. and FUKUMOTO. T. (1~81): reagent for the conversion of hydroxy acids A simple method for esterification of car­ to macrolactones by double activation boxylic acids using chlorosilane, Bull. methods, Tetrahedron Lett., 3409. Chem. Soc.Jap. 54(4): 1267 - 8. - CEKOVIC, Z., BSNJAK. J. and CVETKOVIC. M. SEKINE, M., KUME. A. and HATA, T. (1981): (1980): Fovorskii type rearrangement in the Acylphosphonate II: Dialkul acylphospho­ lead tetracetate oxidation of enamine pro­ nate; a new acylating agent for alcohols. moted by boron trifluoride, Tetrahedron Tetrahedron Lett. 22(37): 3617 - 80. Lett. 21(27): 2675 - 8. WADE. Jr. L.G. (1981): Compendium of Orga­ COREY, E.J., NICOLAOU. K.C. and MELvIN.Jr, nic Synthetic Methods, Vol. 4, John WHey & L.S. (1975): Synthesis of novel macrocydic Sons, New York, pp. 176 -197. Lactones in the prostaglandin and polyether antibiotic series]. Am. Chern. Soc. 97: 653. REGEN. S.L. and LEE, D.P. (1975): Solid phase phosphorus reagents,]. Org. Chem., 40: COREY. E.J., NICOLAOU, K.C. and MELvIN,Jr, 1669. L.S. (1975): Synthesis of Brefeldin A, Car­ paine, Vertaline and Erythronolide-B from (Received 12 September, 1984)

PERTANIKA VOL. 8 NO.1. 1985 71