Abstract
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, 1H NMR, 13C-NMR and IR.
Highlights
Rapid synthesis of 4-ethyloctanoic acid by means of microwave irradiation is described
In addition to costus root oil, 4-Ethyloctanoic acid occurs in flue-cured virginia tobacco [2], aged Italian cheese [3], sheep cheese [4], goat cheese [5,6] and stewed beef gravy [7]
We investigated the influences of mole ratio of starting materials, reaction temperature and reaction time on the yield of 1b to optimize synthesis conditions
Summary
4-Ethyloctanoic acid was first isolated from the root oil of the Costus plant (Saussurea lappa Clarke) by de Rijke [1]. Powell’s from 2-ethyl-1-bromohexane and diethyl malonate [11] (Scheme 1) This method offers the advantage of cheap and available materials with mild reaction conditions, but requires long reaction times [12,13,14,15]. The fourth method is the synthesis of 4-ethyloctanoic acid by coupling reaction [18] (Scheme 4). This method includes more steps and complex operational conditions. The coupling reaction requires anhydrous conditions and low temperatures (−70 °C), so this method is only suitable for laboratory syntheses.
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