(J.E.TL.1973)β-二羰基化合物在DMSO, NaCl和水体系中脱羧基

Tetrahedron Letters No. 12, pp 957 - 960, 1973. Fer,Tamon Press. Printed in Crest Britain. DECMBALKOXTLATION.9 OF GIPIINAL DIESTIERS, B-IUITO gS!lZRS AND a-CYAN0 ESTERS EFFECTED BY SODIUM CWLORIDE IN DIMETDTL SuLPCxIDg A. Paul Krepcho and Allen J. Lowey Department of Chemistry, The University of Vermont Burlington, Vermont 05401 (Received in USA 16 January 1973; received in UK for publication 10 February 1973) we wish to report that decarbalkoxylatlons of geminal diesters, g-keto esters, snd e-cyan0 esters to the corresponding esters, ketones, and nitrlles can be effected in excellent yields by sodium chloride in wet dimethyl sulfoxide at temperatures of MO-186.. This novel salt-solvent system avoids the hazardous use of sodium cyanide previously reported by us to effect decarbalkoxy- lations of gemlnal dlesters (1,Z). A variety of mono- and disubstituted diethyl malonates have been decarbethoxylated by NaCl- wet DMSO and the results are tabulated in Table I. In all cases the yields of the esters are In the 90-953 range. The applicability of the NaCl-wet DWSO system for the decarballcoxylatlon of B-keto esters and a-cyano esters is Illustrated by the reactions summarized in Table II. Again excellent yields of products are obtained. Carbon dioxide and ethanol are produced in the reaction. The loss of carbon dioxide served as a convenient probe for determining the minimum reaction temperature necessary to initiate the decarbethoxylatlon. Water ia necessary to effect the reaction since use of snhydrous DMSO leads to little or no reaction. General Procedure: The DMSO (Fisher certified grade) was used as received. Approximately 2 moles of water per mole of subetrate was added to the DMSO. A alight excess of sodium chloride was wed in most of the reactions. Sterling commercial uniodized table salt is satisfactory. The reaction mixture Is magnetically stirred and the apparatus Is fitted with an internal thermometer and a condenser. A trap containing e solution of barium hydroxide is connected to the apparatus through the top of the condenser. The reaction mixture is heated using an oil bath until no further evolution of carbon dioxide can be detected, 957 958 No. 12 TABLE I DECARBALWXYLATIONS OF CRMINAL DIESTRRS BY NaCl IN WET DMSO RRlC(COp2 - RRlCHCO2Et + CO2 + CH3CH2OH DIESTER ---f ESTERa TEMP (HRS) b R-R -11 C 1 140-165 (6) R=li,R -CH 3= 1 153-175 (4) R=H,R = 1 CH3CH* d 153-165 (4) R=B,R - CH3(CH2)15= 1 158-170 (5) R=H,R - CH3(CH2)21e l 154-170 (6) R=H,R - 0c 1 135-170 (2) R-H,R I- 0CHz e 155-170 (3) R-&R -CH=CHCH= 12 2 153-165 (4) R-R =CH 3= 1 175-180 (6) Rs R1 - CH2CH2CH2 f 178-183 (4) aBstere were isolated in 90-95X yields except in entries 1, 2, and 3 where the yiel& were calculated to be 85-95X from nmr analysis of the crude products. Ethanol was difficult to remove from these low boiling esters. b 'Ihe minimum temperature is the point at bhich carbon dioxide evolution commenced. The temoerature was then slowly raised to the maximum temperature listed over the period of time given in parenthesis. '0.10 moles d0.07 moles '0.04 moles f 0.04 moles of diester, 0.11 wles NaCl, 0.20 moles of water in 50 ml DMSO. dieater, 0.006 moles NaCl, 0.10 moles of water in 50 ml DMSO. dieater, 0.05 moles NaCl. 0.15 moles of water in 30-40 ml DMSO. diester, 0.07 moles NaCl, 0.11 moles of water in 80-90 ml DMSO. The isolation procedure depends on the properties of the product. Low boiling substrates (entries 1, 2, 3 in Table I and all entries of Table II) were distilled from the reaction. No further attempt was made to remove the co-distilled alcohol from theee products. The higher boiling esters (entries 6 through 10 in Table I) were isolated by addition of water to the reaction mixture and separation of the ester layer. The aqueous layer was extracted with ether and the ester puri- fied by distillation. The solid eaters (entries 4 and 5 in Table I) were filtered from the Cool reaction mixture and dissolved in ether. The ethereal solution was washed with water, dried, and the ether removed. The ester was recrystallized from ethanol. changhe Pencil No. 12 959 TASLR II DECARRETSOXyI..ATIONS OF 8-RRTC ESTERS AND a-CYAN0 RSTRRS REACTANT PRODI& 0 0 C02Rb*= 0 C02RC'd 0 TENP (&IRS) 120-150 (5) 130-150 (2) 0 II ~~(~2yC-CH3c Is cH3 (CR21 pcH3 153-165 (5) C02Et NCCH2C02Ete cH3cNf 135-165 (2) cH3(CH ) clicN= 2 31 C02Et 'Isolated in yields of 85-95X. Q$ (CH2) 4cN 152-168 (2) bArapshoe Chemicals sample which by nmr analysis contains 35% and 65% methyl and ethyl esters, respectively. '0.065 moles of B-keto ester, 0.07 smles NaCl, 0.20 moles of water In 30-50 ml DMSO. a Arapahoe Chemicals aample which by nmr analysis contains equal mounts of the methyl and ethyl esters. '0.09 moles a-cyano ester, 0.03 moles NaCl, 0.20 moles of water In 60 ml DMSO. fContaminated with ethanol and a little DMSO. The effect of NaCl is catalytic as can be noted from entry 3 of Table I where a lo-fold molar excess of the diester over that of the salt was used and a 90% yield of the ester was obtained. For the diesters reported in Table I, diethyl phenylmalonate undergoes the most facile decarbethoxy lation while diethyl dlmethylmalonate and dlethyl cyclobutanedicarboxylate undergoes the slowest decarbethoxylation. It, therefore, seems reasonable to propose from the limlted data at hand that the decarbethoxylation proceeds via a nucleophilic catalysis mechanism. The nucleophilic attack of chloride ion. which is expected to be a strong nucleophile in a dipolar aprotic solvent such as DhSO (31, on one of the ester groups would lead to an Intermediate such as I. Cleavage of the changhe Pencil changhe Pencil 960 No, 12 C-C bond would lead to the carbanion II and ethyl chloroformate (III). Protonation of IL by water Yco2Et - I+CO,Et + C1C02Et - O?--OEL Cl I II III would lead to the ester aud hydrolysis of III would regenerate the chloride ion and liberate alcohol and carbon dioxide. The decarbethoxylatlon ease of the dleeters follows the carbanion stability of II. Successful decarbethoxylatlons have been accomplished using alkali metal fluorides, bromides. chlorldee, sodium azide, and sodium phosphate. Other dipolar aprotic solvents such as dimethyl forxamide (bp 153') have been utilized successfully. The decarbethoxylation of diethyl phenyl- m&mate with DMP-NaCl-water proceeds in an excellent yield. However, In less reactive substrates such as diethyl dlmethylmalonate longer heating times must be employed because of the lower boiling (bp 189'). point of DMP to that of DMSO Detailed studies on the will be reported in the near above salts, other dipolar aprotic solvents, and additional substrates future in a full paper. Acknowledgment The authors are indebted to The Humphrey Chemical Company, North Haven, Connecticut 06473, for their interest in this research and partial financial support. RRPRRWCES 1. a. A. P. Krapcho, G. A. Clynn, and B. G. Grenon, Tetrahedron Letters, 215 (1967). b. A. P. Krapcho and B. P. Mundy, Tetrahedron, 26, 5437 (1970). 2. Other subsequent applications of this method have appeared: a. W. S. Johnson, C. A. liarbert, and R. D. Stipanovic, J. Amer. Chem. Sot., 90, 5279 (1968). b. J. Harley-Mason and Atta-ur-Rahman, Chem. & Ind. (London), 1845 (1968). c. M. Pieser and L. Fieser, "Reagents for Organic Synthesis," Vol 2, p 381; Wiley-Intersclence (1969). 3. J. Parker in "Advances on Organic Chemistry, Method and Results," Vol 5, p 1, Interscience (1965).