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A solution of L-proline (2.23 g) in dry methanol (15 ml) was cooled to -5 C. and thionyl chloride (4.52 g) was added dropwise, while stirring and maintaining the temperature of the reactants below 0 C. The reaction was continued at 25 C. for 2 h. The solvent was distilled and the residue stored in ice-chest for 12 h. The solid mass was added to aqueous solution of potassium carbonate (50%, 20 ml) at 0 C. and the separated oily layer was extracted into ether (15 ml×3). The ethereal layer was dried over anhydrous sodium sulfate and distilled to afford 2.3 g of 2-(carbomethoxy)-pyrrolidine (85%), [MS (m/z) M+129 (1%), 114 (0.5), 70(100), 68(50), 43(80), 41(90)]. It was taken in dry diethyl ether (15 ml), cooled to 0 C. and t-butylhypochlorite (2.16 g) added dropwise. The reaction was monitored on silica gel thin layer using chloroform as the eluant. After completion of the reaction (15 min.), potassium t-butoxide (2.24 g) was added gradually over 10 min. and the reactants stirred at 25 C. for 5 h. The solution was filtered and the solvent distilled under reduced pressure to afford 2-(carbomethoxy)-1-pyrrroline (2 g), [MS (m/z) M+ 127(1%), 112(0.5), 97 (15), 69 (100), 54 (50), 41 (75)]. To a suspension of magnesium turnings (0.43 g) in dry ether, iodine (0.01 g) was added followed by dropwise addition of a solution of methyl iodide (3.08 g) in ether (5 ml) at 35 C. The mixture was stirred until the disappearance of magnesium turnings (15 min), then cooled to 0 C. To it, a solution of 2-(carbomethoxy)-1-pyrrroline (2 g) in dry ether (5 ml) was added over 5 min. and the mixture was stirred at room temperature. On completion of the reaction (2 h) the product was worked up by the addition of dilute hydrochloric acid (5%, 10 ml) and the organic layer separated. The aqueous layer was further extracted with ether (10 ml×2) and the combined organic layers dried over anhydrous sodium sulphate and distilled to afford pure 2-acetyl-1-pyrroline [1.3g, 95% purity, [MS (m/z) M+ 111 (5%), 96 (0.1), 83 (15), 69(8), 68 (10), 55 (2), 52 (0.2), 43 (100),42 (25), 41 (50)]. |
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To a solution of L-proline (2.23 g) in dry methanol (15 ml) cooled to -5 C., thionyl chloride (4.52 g) was added drop wise, while stirring and maintaining the temperature of the reactants below 0 C. The reaction mixture was allowed to attain room temperature (25 C.) and further stirred for 2 h. The solvent was distilled off from it and the residue stored in ice-chest for 12 h. The solid mass that separated was added to an aqueous potassium carbonate solution (50%, 20 ml) at 0 C. and the separated oily layer extracted into ether (15 ml×3). The combined ethereal layers were dried over anhydrous sodium sulfate and distilled to afford 2.3 g of 2-(carbomethoxy)-pyrrolidine [85%, MS (m/z) M+129 (1%), 114 (0.5), 70(100), 68(50), 43(80), 41(90)]. To an ice-cooled solution of the compound in dry diethyl ether (15 ml), t-butylhypochlorite (2.16 g) was added drop-wise. The reaction was monitored on thin layer of silica gel using chloroform as the eluant. After 15 min. anhydrous potassium acetate (2.76 g) was added gradually added to it over 10 min., and the mixture stirred at 25 C., while monitoring the reaction by TLC. At the end of the reaction (3 h), the solution was filtered and the solvent distilled under reduced pressure to afford 2-carbomethoxy)-1-pyrrroline [Yield: 1.9 g, MS (m/z) M+ 127(1%), 112(0.5), 97 (15), 69,(100), 54 (50), 41 (75)]. To a suspension of magnesium turnings (0.43 g) in dry diethylether, iodine (0.01 g) was added followed by a solution of methyl iodide (3.08 g) in ether (5 ml) dropwise at 35 C. The mixture was stirred until the disappearance of magnesium (15 min) and then after cooling to 0 C., a solution of 2-(carbomethoxy)-1-pyrrroline (1.9 g) in dry diethylether (5 ml) was added over 5 min. On completion of the reaction (2 h) as found by GC, the product was worked up by addition of dilute hydrochloric acid (5%, 10 ml) and separation of the organic layer. The aqueous layer was further extracted with diethylether (10 ml×2) and the combined organic layers dried over anhydrous sodium sulphate. Removal of the solvent afforded pure 2-acetyl-1-pyrroline [1.2 g, 95% purity, MS (m/z) M+ 111 (5%), 96 (0.1), 83 (15), 69(8), 68 (10), 55(2), 52 (0.2), 43 (100), 42 (25), 41 (50)]. |
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