Studies on pyrimidine derivatives and related compounds. XCIV. On the oxidation products of 2-substituted-2,3-dihydro-4H-1,4-thiazin-3-one derivatives.

Abstract

Hydrogen peroxide oxidation of 4-(4-amino-2-methylpyrimidin-5-yl) methyl-6-(2-hydroxyethyl)-2-(2-methoxyphenyl)-4-methyl-2, 3-dihydro-4H-1, 4-thiazin-3-one (1c) gave N-[(4-amino-2-methylpyrimidin-5-yl)methyl]-N-[1-(2-oxido-1, 2-oxathiolan-3-yliden)ethyl] (2-methoxyphenyl)oxalamide (3b) and 2-oxido-1, 2-oxathiolane-3-spiro-3'-[1'-(4-amino-2-methylpyrimidin-5-yl)methyl-4'-hydroxy-2'-methylene-4'-(2-methoxyphenyl)-tetrahydropyrrol-5'-one] (6). The former product (3b) was transformed into another product (6) under oxidative reaction conditions and 6 led to the known 1-(4-amino-2-methylpyrimidin-5-yl)methyl-4-hydroxy-3-(2-hydroxyethyl)-4-(2-methoxyphenyl)-2-methyl-Δ2-pyrrolin-5-one (4) and 2-aza-2-(4-amino-2-methylpyrimidin-5-yl)methyl-4-hydroxy-4-(2-methoxyphenyl)-1-methyl-8-oxabicyclo [3.3.0] octan-3-one (5) on acid or alkali treatment. On the other hand, an oxalamide (3d) having a 2-anisyl substituent was recovered under the same reaction conditions. The same reaction with 2-aryl-4-benzyl-2, 3-dihydro-4H-1, 4-benzothiazin-3-ones (12a-c) afforded 2-aryl-4-benzyl-2-hydroxy-2, 3-dihydro-4H-1, 4-benzothiazin-3-ones (13a-c), bis-(2-aryloxalylaminophenyl)-1, 1'-disulfide (14a-b) and 2-aryl-4-benzyl-3-oxo-2, 3-dihydro-4H-1, 4-benzothiazine-1, 1-dioxide (15a-c), while 4-benzyl-2-methyl-2, 3-dihydro-4H-1, 4-benzothiazine-1, 3-dioxide (16b) was mainly obtained in the oxidation of the 2-methyl derivative (12d), which was converted into 4-benzyl-2-hydroxy-2-methyl-2, 3-dihydro-4H-1, 4-benzothiazin-3-oxide (13d) via a Pummerer-type rearrangement. The reaction mechanism is discussed.