Synthesis and Structure of (E)-1-(3-Methylsulfanyl-1,2,4-triazin-5-yl)-ethanone O-Acryloyl Oxime.DAGGER.

Abstract

The reaction of 1,2,4-triazines with alkyl nitronate anions has shown considerable synthetic utility, and allows a highly efficient entry into oximes of alkyl (1,2,4-triazyn-5-yl) ketones. 1 The latter may serve as common intermediates in the construction of pyrazolo [4,3-e][1,2,4]triazines, 2 2-acylpyridines and 3-acyl-5,6,7,8-tetrahydroisoquinolines, valuable precursors for the synthesis of sempervirine, and its analogues, 3 possessing interesting pharmacological activity. In view of the wide application of the 1,2,4-triazine oximes in organic synthesis, unequivocal assignments of their stereochemistry became indispensable. The configuration of alkyl-1,2,4-triazin-5-yl ketooximes was determined previously by means of 1 H-NMR, 13 C-NMR, and homonuclear NOE-difference spectroscopy. 4 Oximes resulting from reaction of 1,2,4-triazines with nitronate anions were found to be either pure E-isomers or E/Z-mixture with the amount of E-isomer greatly predominating. Here, we have extended this study to a single-crystal X-ray diffraction structure of 1-(3-methylsulfanyl)-1,2,4-triazin-5-yl)ethanone Oacryloyl oxime, simply obtained by the reaction of 3-bromopropanoyl chloride with oxime of 5-acetyl-3-methylsulfanyl-1,2,4-triazine in the presence of triethylamine. Attempts to obtain mono crystals of the oximes of alkyl (1,2,4-triazyn-5-yl)ketones suitable for X-ray analysis, failed.5-Acetyl-3-methylsulfanyl-1,2,4-triazine was prepared as a reference.4 (E)-1-(3-Methylsulfanyl)-1,2,4-triazin-5-yl)-ethanone O-acryloyl oxime was synthesized according to the following procedure: to a solution of oxime of 5-acyl-3-methylsulfanyl-1,2,4-triazine (1.5 mmol) and triethylamine (4.5 mmol) in dry CH2Cl2 (5 mL) at -40˚C was added the acid chloride (1.5 mmol) in CH2Cl2 (2 mL), dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 12 h. It was then washed with water (2 × 10 mL), saturated aqueous sodium bicarbonate (3 × 10 mL), brine (1 × 10 mL) and dried over MgSO4. Removal of the solvent yielded a crude product, which was then purified by column chromatography on silica gel using CH2Cl2/hexane mixture (2:1) as an eluent. Yield, 81%; m.p., 99 -100˚C. 1 The title compound, C9H10N4O2S, crystallizes in the triclinic system, space group P1, with cell constants a = 7.5330 (2)

(E)-1-(Pyridin-2-yl)ethanoneO-acryloyloxime

“…The geometric parameters (bond lengths, angles and torsion angles) in the title compound are very similar to those observed in a previously reported structure of (E)-1-(3-methylsulfanyl-1,2,4-triazin-5-yl)-ethanone O-acryloyl oxime (Mojzych et al, 2007). The oxime group is in trans and the acryloyl group in s-cis conformation with the torsion angles O1-N2-C6-C5 and O2-C7-C8-C9 of 179.39 (7) and 2.73 ( 16)°, respectively.…”

“…For the biological activity of oximes, see: Van Helden et al (1996). For related structures, see: Mojzych et al (2007). For the graph-set notation, see: Bernstein et al (1995).…”