Novel Synthesis of <alpha>-Amino Ketones Using the Characterristics of Sulfur Compounds

Research Project

Project/Area Number	61550629
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Synthetic chemistry
Research Institution	Chiba University
Principal Investigator	OGURA Katsuyuki Faculty of Engineering, Chiba University, Professor, 工学部, 教授 (60114253)
Project Period (FY)	1986 – 1987
Project Status	Completed (Fiscal Year 1987)
Budget Amount *help	¥2,000,000 (Direct Cost: ¥2,000,000) Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000) Fiscal Year 1986: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywords	<alpha>-amino ketones / ketene dithioacetal S,S-dioxides / MT-sulfone / 有機合成反応 / メチルチオ基 / スルホニル基 / 硫黄
Research Abstract	In the present project, a novel method was established for synthesizing N-mono-substituted <Alph>-amino ketones (1) which are useful synthetic intermediates of medicines and agricultural chemicals. The investigated method comprizes three processes: (i) the addition of an amine to a ketene dithioacetal S,S-dioxide (2) to give an adduct; (ii) alkylation of the thus-obtained adduct (3); and iii) the subsequent acidhydroxylsis leading to an <alph>-amino ketone (1). We have found that a primary amine irreversibly adds to 2 to afford the adduct (3) in a good yield. In the reaction with an alkyl iodide in the presence of NaH in DMF at 0 ゜C to room temperature, 3 afforded a Calkylation product (4), which was subjected to the subsequent hydrolysis without any isolation. For hydrolysis of 4, employment of the higher concentration of hydrochloric acid was found to be crucial to smooth hydrolysis. Thus, refluxing (2-4 h) of the slution of crude 4 in a 1:4 mixture of conc hydrochloric acid and methanol gave the best result. Thus we established a convenient method for the preparation of <alpha>-amino ketones (1).