Synlett, Table of Contents Synlett 2012; 23(14): 2093-2097DOI: 10.1055/s-0031-1290449 letter © Georg Thieme Verlag Stuttgart · New York Lewis Acid Mediated Selective Monohydrolysis of Geminal Diesters: Synthesis of Functionalized Malonic Acid Half Esters Andivelu Ilangovan* a School of Chemistry, Bharathidasan University, Palkalaiperur, Tiruchirappalli 620024, India, Fax: +91(431)2407045 Email: ilangovanbdu@yahoo.co.in , Rajendran Ganesh Kumar a School of Chemistry, Bharathidasan University, Palkalaiperur, Tiruchirappalli 620024, India, Fax: +91(431)2407045 Email: ilangovanbdu@yahoo.co.in , Mahabir Prasad Kaushik b Process Technology Development Division, Defense Research and Development Establishment, Jhansi Road, Gwalior 474002, India › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract Geminal diesters, N-alkyl/aryl-2,2-bis(ethoxycarbonyl)vinylamines, were found to undergo selective hydrolysis in the presence of BF3·OEt2 at room temperature to give the corresponding half esters. Neighboring group participation by nitrogen in the hydrolysis was observed. This method is useful for the preparation of highly functionalized malonic acid half esters. Key words Key wordsLewis acid - boron trifluoride - geminal diesters - hydrolysis - esters Full Text References References and Notes 1a Guler MO, Stupp SI. J. Am. Chem. Soc. 2007; 129: 12082 1b Drescher M, Hammerschmidt F, Kählig H. Synthesis 1995; 1267 2 Iosub V, Haberl AR, Leung J, Tang M, Vembaiyan K, Parvez M, Back TG. J. Org. Chem. 2010; 75: 1612 3 Pridmore SJ, Williams JM. J. Tetrahedron Lett. 2008; 49: 7413 4 Ryu Y, Scott AI. Tetrahedron Lett. 2003; 44: 7499 5 Kanth JV. B, Periasamy M. J. Org. Chem. 1991; 56: 5964 6 Baudoux J, Lefebvre P, Legay R, Lasne M.-C, Rouden J. Green Chem. 2010; 12: 252 7a Niwayama S, Cho H, Moghaddam MZ, Whittlesey BR. J. Org. Chem. 2010; 75: 3775 7b Niwayama S, Cho H. Chem. Pharm. Bull. 2009; 57: 508 7c Niwayama S. J. Org. Chem. 2000; 65: 5834 7d Durham LJ, McLeod DJ, Cason J. Org. Synth. Coll. Vol. IV 1963; 635 8a de María PD, Burgos CA. G, Bargeman G, van Gemert RW. Synthesis 2007; 1439 8b Liang X, Lohse A, Bols M. J. Org. Chem. 2000; 65: 7432 8c Kedrowski BL. J. Org. Chem. 2003; 68: 5403 9a Abaee MS, Sharifi R, Mojtahedi MM. Org. Lett. 2005; 7: 5893 9b Corma A, García H. Chem. Rev. 2003; 103: 4307 10 Sabitha G, Srividya R, Yadav YS. Tetrahedron 1999; 55: 4015 11 Basso A, Banfi L, Riva R, Guanti G. J. Org. Chem. 2005; 70: 575 12 Englund EA, Gopi HN, Appella DH. Org. Lett. 2004; 6: 213 13 Shapira M, Gutman AL. Tetrahedron: Asymmetry 1994; 5: 1689 14 Ilangovan A, Kumar RG. Chem.–Eur. J. 2010; 16: 2938 15 McQuaid KM, Long JZ, Same D. Org. Lett. 2009; 11: 2972 16 Yamada K, Maekawa M, Akindele T, Nakano M, Yamamoto Y, Tomioka K. J. Org. Chem. 2008; 73: 9535 17 Kim BM, So SM. Tetrahedron Lett. 1998; 39: 5381 18 Carruthers W, Qureshi M. J. Chem. Soc. C 1970; 2238 19 Komatsu H, Iwasawa N, Citterio D, Suzuki Y, Kubota T, Tokuno K, Kitamura Y, Oka K, Suzuki K. J. Am. Chem. Soc. 2004; 126: 16353 20 Kaul R, Brouillette Y, Sajjadi Z, Hansford KA, Lubell WD. J. Org. Chem. 2004; 69: 6131 21 Mattsson S, Dahlstrom M, Karlsson S. Tetrahedron Lett. 2007; 48: 2497 22 Bruice BY. Organic Chemistry . Prentice Hall; Englewood Cliffs: 1995. Chap. 24 § 23a Walder JA, Johnson RS, Klotz IM. J. Am. Chem. Soc. 1978; 100: 5156 23b Sugiura M, Robvieux F, Kobayashi S. Synlett 2003; 1749 23c Bethell D. Advances in Physical Organic Chemistry . Academic Press; New York: 1993. 28 and 17 23d Bowden K. Chem. Soc. Rev. 1995; 24: 431 24 Compound 6a and 8a both belong to a monoclinic system with space group P21/n and P21, respectively. Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre [CCDC-832627 (6a) and 832624 (8a)]. The crystal information file (CIF) can be obtained free of charge from www.ccdc.cam.ac.uk/products/csd/request/. 25 Half esters of substituted aniline were coupled with some substituted aniline and amino acid methyl esters to obtain novel amide derivatives such as (E)-ethyl 2-(2-bromophenylcarbamoyl)-3-(phenylamino)acrylate and found to show good antibacterial (e.g., E. coli) and antifungal (e.g., C. albicans) activity. 26 For details on racemization, isomerization and in situ NMR studies see the Supporting Information. 27 Bruice TC, Sturtevant JM. J. Am. Chem. Soc. 1959; 81: 2860 28 McCoy PC, Morrow RJ, Edwards CR, Jones DS, Gorman SP. Bioconjugate Chem. 2007; 18: 209 29 General procedure for BF3·OEt2-mediated hydrolysis of diethyl 2-[(aryl/alkyl-amino)methylene]malonate: To a solution of diethyl 2-[(aryl/alkyl-amino)methylene]-malonate (1.0 equiv) in chloroform (3 × w/v), BF3·OEt2 (1.0 equiv) was added and the mixture was stirred at r.t. under a nitrogen atmosphere (the reaction was monitored by TLC). Upon completion, the reaction mixture was quenched with water (1 × w/v) and extracted with chloroform (3 × 5 mL). The combined organic layer was dried (anhyd. Na2SO4) and evaporated in a rotary evaporator. The crude product was passed through a short column (silica gel) using a suitable eluent to obtain the corresponding product in 40–92% yield. Preparation of 2-(p-tolylaminomethylene)malonic acid monoethyl ester (2b): The reaction was carried out according to the general procedure using diethyl 2-(p-tolylaminomethylene)malonate1 (1b; 500 mg, 1.8 mmol), and BF3·OEt2 (453 μL, 1.8 mmol) in chloroform (1.5 mL) at r.t. for 20 min. The title compound 2b (0.40 g, 90%) was obtained as a white solid after passing through a short silica gel column (hexane–EtOAc, 9:1). Mp 92 °C; 1H NMR (400 MHz, CDCl3): δ = 1.35 (t, J = 7.2 Hz, 3 H), 2.33 (s, 3 H), 4.32 (q, J = 7.2 Hz, 2 H), 7.06 (d, J = 8.4 Hz, 2 H), 7.18 (d, J = 8.4 Hz, 2 H), 8.44 (d, J = 13.6 Hz, 1 H), 11.62 (d, J = 13.2 Hz, 1 H), 13.0 (br s, 1 H); 13C NMR (100 MHz, CDCl3): δ = 14.3, 20.7, 61.3, 89.0, 177.7, 130.3, 135.9, 136.0, 151.6, 169.9, 170.7; IR (KBr): 3183, 2978, 2688, 1696, 1630, 1512, 1473, 1407, 1268, 1205, 1089, 1017, 887, 831, 811 cm–1; MS: m/z calcd. for C13H15NO4: 249.10; found: 250.2 [M + 1]; Anal. Calcd for C13H15NO4: C, 62.64; H, 6.07; N, 5.62. Found: C, 62.62; H, 6.08; N, 5.60. Supplementary Material Supplementary Material Supporting Information
