Reaction of some heterocyclic ketones with acetonitrile in an acid medium

Abstract

In previous work [1], we have shown that the reaction of substituted 4-piperidones with four equivalents of acetonitrile in the presence of sulfuric acid leads to the formation of the corresponding bisamides, namely, 4,4-diacetylaminopiperidines. We then undertook a study of the feasibility of obtaining bisamides from other saturated heteroeyclic ketones.We attempted to obtain bisamides by analogy with our previous procedure [1] from several tetrahydro-4-thiopyranones and tetrahydro-4-pyranones. 2,5-Dimethyl-(Ia) and 3-methyl-2-phenyltetrahydro-4-thiopyranones (Ib) were found to react with acetonitrile over 24 h at 20~ The reaction ratio was 1:4 or 1:2. In the ease of ketone Ia, extraction of the reaction mixture with hot hexane gave 4-acetylamino-3,6-dimethyl-5,6-dihydro-2H-thiopyran (IIa) in 30% yield, mp 107-108~ (from hexane). IR spectrum: -1510 (NH def), 1630-1670 (amide C =O and C =C), -3200 cm -1 (NH, stretching). PMR spectrum in CDC13:1.28 (3H, d, 6-CH3), 1.7 (3H, s, 3-CH3), 2.04 (3H, s, COCH3), 2.15 and 2.63 (5-CH2), 2.92 and 3.45 (2-CH~, 3.05 (1H, m, 6-Ha), 6.75 ppm (1H, br.s, NH), Jza2e = Jsase = 17.1, J5a6a = 10.2, Jseta = 3.9, J6aCH 3 = 6.84 Hz. Under the same conditions, ketone Ib gives a mixture of compounds. PMR spectroscopy indicated that the major component is diamide IIb. PMR spectrum in CDCI3: 0.86 (3H, d, 3-CH3), 1.99 (3H, s, COCH3), 2.16 (3H, s, COCH3), 2.7-3.3 (5-CH 2 and 6-CH2), 3.82 ppm (1H, d, 2-Ha). However, attempts to isolate pure diamide IIb were unsuccessful.The reaction of 3,5-dimethyl-2,6-diphenyltetrahydro-4-pyranone with acetonitrile in acid medium under the same conditions is accompanied by ring opening and formation of a mixture of alicyclic compounds as indicated by PMR spectroscopy. The structures of these products were not studied.It is interesting to note that 1-acetyl-4-piperidone 011) was recovered quantitatively in all eases when we attempted to carry out the reaction of this piperidone with acetonitrile in acid medium at 20~ over 12 days and at 60"C ovor 2 h (the reagent ratio was 1:2 or 1:4). Thus, a reduction in basicity makes the formation of bisamides impossible even for 4-piperidones.We attempted to convert 1-methyl-4-piperidone (IV) into the corresponding amidoketone, namely, 2-(4-aeetylamino-1-methyl-4-piperidyl)-l-methyl-4-piperidone by analogy with the results of Koehetkov et al. [2], who discovered a similar reaction for cyclohexanone. However, piperidone IV does not undergo reaction under these conditions. When the piperidone-M. V. Lomonosov Moscow State Fine Chemical Technology Academy, 117571 Moscow.