College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.
Int J Mol Sci. 2010 Oct 25;11(10):4165-74. doi: 10.3390/ijms11104165.
Rapid synthesis of 4-ethyloctanoic acid by means of microwave irradiation is described. Diethyl malonate reacted with 2-ethyl-1-bromohexane in the presence of sodium ethoxide to give diethyl (2-ethylhexyl)malonate (1b). 1b was saponified in the solution of ethanol and potassium hydroxide and then acidified to form (2-ethylhexyl)propanedioic acid (1c), and 1c was heated and decarboxylized to give 4-ethyloctanoic acid (1d). The influence of reaction temperature and reaction time on the yield of 1b and the effect of reaction time on the yield of 1c and 1d were investigated in order to optimize the synthetic conditions. The relative optimal conditions for the synthesis of 1b were a mole ratio of sodium to diethyl malonate to 2-ethylhexyl bromide of 0.1:0.11:0.11, a reaction temperature of 80-85 °C, and a reaction time of 2-2.5 h. The yield of 1b was about 79%. 1b was saponified for 30 min and then acidified to form 1c, and the yield of 1c was 96%. 1c was heated for 16 min at 180°C to give 1d, and the yield of 1d was about 90%. The overall yield of 1d is 70% under microwave irradiation. The reaction time was reduced greatly. In order to compare the result of microwave irradiation with that of an oil bath, the reactions were also performed in an oil bath. The structures of intermediates, product and by-product were confirmed by HRMS, (1)H NMR, (13)C-NMR and IR.
微波辐射促进的 4-乙基辛酸的快速合成。丙二酸二乙酯与 2-乙基-1-溴己烷在乙醇钠存在下反应得到二乙基（2-乙基己基）丙二酸酯（1b）。1b 在乙醇和氢氧化钾的溶液中皂化，然后酸化得到（2-乙基己基）丙二酸（1c），1c 加热脱羧得到 4-乙基辛酸（1d）。考察了反应温度和反应时间对 1b 产率的影响，以及反应时间对 1c 和 1d 产率的影响，以优化合成条件。1b 的合成的相对最佳条件为：钠与丙二酸二乙酯摩尔比与 2-乙基己基溴的摩尔比为 0.1:0.11:0.11，反应温度为 80-85°C，反应时间为 2-2.5 h。1b 的产率约为 79%。1b 皂化 30 min 后酸化得到 1c，1c 的产率为 96%。1c 在 180°C 下加热 16 min 得到 1d，1d 的产率约为 90%。在微波辐射下，1d 的总产率为 70%。反应时间大大缩短。为了将微波辐射的结果与油浴的结果进行比较，反应也在油浴中进行。中间体、产物和副产物的结构通过高分辨质谱（HRMS）、（1）H NMR、（13）C-NMR 和 IR 得到确认。
