The dimroth rearrangement. Part XIV. The preparation and rearrangement of 1,6-dihydro-6-imino-1-methylpyrimidine

Abstract

3-Methyl-2,4-dithiouracil (6; X = S, R = H) undergoes preferential 2-S-methylation to give 3-methyl-2-methyl-thiopyrimidine-4(3H)-thione (7; X = S, R = SMe), which reacts further with methyl iodide to give 1-methyl-2,6-bismethylthiopyrimidinium iodide (11). Subsequent ammonolysis affords 1,6-dihydro-6-imino-1-methyl-2-methylthiopyrimidine (2; R¹= H, R²= SMe), which may be desulphurised by Raney nickel to yield 1,6-dihydro-6-imino-1-methylpyrimidine (2; R¹= R²= H). The former imine does not undergo Dimroth rearrangement; the second rearranges twelve times faster than its 1,2-dihydro-2-imino-isomer (1; X = NH, R = H).

The Whitehead condensation of ethyl ethoxymethylenecyanoacetate and N-methylthiourea at 25° gives not only ethyl 6-amino-1,2-dihydro-1-methyl-2-thioxopyrimidine-5-carboxylate (5; X = S, R = CO₂Et), as recorded in the literature, but also some 5-cyano-3-methyl-2-thiouracil (6; X = O, R = CN); the latter product predominates when the condensation is done under reflux. Against all precedent, the analogous condensation of ethoxymethyleneacetonitrile and N-methylthiourea gives 1-methyl-2-thiocytosine (1; X = S, R = NH₂) instead of the 3-methyl isomer.

Structures were confirmed by ¹H n.m.r. spectra; also by syntheses of (inter alia) 5-carboxy-3-methyl-2-thiouracil, 6-amino-1,2-dihydro-1-methyl-2-thioxopyrimidine-5-carboxylic acid, 1-methyl-6-methylthiopyrimidine-2(1H)-thione, its 2-oxo-analogue, and its 2-methylthio-4(1H)-thione isomer, 1,6-dihydro-1-methyl-6-methylimino-2-methylthiopyrimidine and its 1,4-dihydro-4-methylimino-isomer, 1,2-dihydro-1-methyl-6-methylamino-2-methyliminopyrimidine, and 4-methylamino-2-methylthiopyrimidine.