Synthesis of O-alkyl, or O-acyl derivatives of 2-propylpentanohydroxamic acid

Abstract

This investigation was to study the synthetic route of o-alkyl, or O-acyl-2 propylpentanohydroxamate which were expected to be novel imidooxy liked anticonvulsants. The formation of O-alkyl-2-propylpentanohydroxamate proceeded through 3 steps. Firstly, 2-propylpentanoic acid was chlorinated by using thionyl chloride to form 2-propylpentanoyl chloride. Secondly, 2- propylpentanoyl chloride reacted to hydroxylamine to obtain 2- propylpentanohydroxamic acid. Finally, 2-propylpentanohydroxamic acid was alkylated by alkyl halides or alkyl sulfate, including ethyl chloroacetate, dimethyl sulfate, ethyl iodide, propyl bromide, benzyl chloride, and a-bromo- 2-chlorotoluene, in the presence of sodium hydroxide solution and heat under reflux. The synthesis of O-acyl-2-propylpentanohydroxamate proceeded through 4 steps. Two firstly steps were similar to the synthesis of O-alkyl-2- propylpentanohydroxamate. But third step, the 2-propylpentanohydroxamic acid was converted to sodium 2-propylpentanohydroxamate by using sodium ethoxide. Finally, the salt was acylated by acyl halides or acid anhydride, including ethyl chloroformate, acetic anhydride, benzoyl chloride, 4-nitrobenzoyl chloride, at 0-10 c. Exceptionally, 2-propylpentanohydroxamic 4-aminobezoic anhydride was prepared from reduction by catalytic hydrogenation of 2- propylpentanohydroxamic 4-nitrobenzoic anhydride using palladium/carbon as a catalyst. In the preparation of all O-acyl-2-propylpentanohydroxamate, N,N'- di(1-propylbutyl)urea was easily formed as a major product by rearrangement of the required compounds under the influence of bases or heat.The chemical structures of the synthesized, and rearranged compounds were confirmed by Infrared Spectrometry, proton-1 and carbon-13 Nuclear Magnetic Resonance Spectrometry, and Mass Spectrometry techniques.