J. Indian Chem. Soc., NOTE Vol. 89, July 2012, pp. 975-979 A convenient procedure for his-esterification of cyclic anhydrides Amit Kumar Jana, Raju Karmakar, Bidyut Kumar Dinda, Prithiba Mitra, Ketaki Ghosh, Rajdip Karmakar and Dipakranjan Mal* Department of Chemistry, Indian Institute of Technology, Kharagpur-721 302, West Bengal, India E-mail : dmal@chem.iitkgp.ernet.in Manuscript received 16 August 2011, accepted 08 November 2011 Abstract : Aromatic and aliphatic cyclic anhydrides are chemoselectively and conveniently transformed to the corres- ponding diesters by the use of DBU and appropriate alkyl/allyl halides. This his-esterification reaction has been exemplified mostly with dimethyl esters. But in some eases, mixed dialkyl esters are also prepared. Keywords : Anhydrides, DBU, his-esterification, chemoselective, mixed dialkyl diesters. Introduction Esterification is a fundamentally important process in organic chemistry. There is a plethora of reported proce- dures in the chemical literature and newer methods are continual! y being developed 1.2. Recent! y, we reported the facility with which DBU-CH 3 I promotes chemoselective esterification of carboxylic acids3· 4 . The conventional lit- erature methods involve retluxing cyclic anhydrides with methanol in presence of an acid catalyst (e.g. HCl 5 , H 2 so 4 6 , PTSA 7 , SOC1 2 8 , etc.). Alternatively, methanolysis of anhydrides followed by treatment with CH 2 Nl or TMSCHN/ is adopted for the preparation of dimethyl esters from cyclic anhydrides. We propose that the reaction of an anhydride (1) with methanol would form a half ester (2), which, in turn, would react with an alkyl halide (Scheme l) to give diester (3) in one operation. This would thus constitute a method, complementary to the commonly used methods 10 . ROH. DIJU R'l 2 3 R, R' = alkyl/allyl Scheme 1. Proposed steps for bis-esteritication of cyclic anhydrides. Results and discussion We began this work with examination of two simple anhydrides, namely succinic anhydride (la) and glutaric anhydride (lb). In both the cases, treatment of these an- hydrides (la and lb) with methanol at room temperature in the presence of DBU (1 equiv) followed by iodomethane (2 equiv) resulted in facile formation of the correspond- ing diesters 3a 11 and 3b 12 • 13 (entries 1 and 2) respec- tively in good yields. The method was then tested with several more complex anhydrides. The results are sum- marized in Table 1. The reaction between the anhydride le with DBU in methanol followed by CH 3 I furnished the dimethyl ester 3e 14 in 77% yield under unoptimized conditions. Conventionally, ketal-containing anhydrides are normally converted to the dimethyl esters in two stages : (i) methanolysis with methanol and (ii) a-methy- lation of the resulting half esters with TMSCHN 1 or Me 2 S0 4 , K 2 C0 3 in DMF5,9, 15. - With a view to developing an operationally simpler method for mixed dialkyl esters, we investigated the re- activity of a series of maleic anhydrides (entries 7-1 0). Maleic anhydride lg was first submitted to the reaction with CH 3 0H-DBU-CH 3 I at room temperature and the desired dimethyl ester 3g 16 was obtained in 71% yield. The isomeric trans diester was not formed 17 . Under iden- tical conditions, methyl maleic anhydride lh afforded cis diester 3h 1 8 in 92% yield. In order to test the feasibility of preparing mixed dialkyl ester, maleic anhydride (lg) was submitted to methanolysis with MeOH in the pres- ence of DBU followed by in situ alkylation with allyl bromide. Work-up of the reaction mixture afforded the 975