Synthesis and structural study of N‐methyl‐2‐methylthiopyrimidine derivatives from trihalomethylated enones

Abstract

The synthesis and chemoselective study of a novel series N-methyl-2-methylthio-tetrahydropyrimidines and or N-methyl-2-methylthiodihydropyrimidines, from the cyclocondensation reaction of b-alkoxyvinyl trihalomethyl ketones (enones) with 1,2-dimethylisothiourea sulfate is described. It was found that the chemoselectivity depends on both the reaction conditions and the steric and electronic effects of the substituents on the enones.

Regioselectively Controlled Synthesis of N-Substituted (Trifluoromethyl)pyrimidin-2(1H)-ones

“…Based on the two-dimensional HMBC NMR experiments, the assignment of the correct position of the N-substituent group in N-substituted 4(6)-(trifluoro­methyl)­pyrimidin-2-ones has been reported for related compounds, which can be seen in Figure . ,, In this experiment, for the 1,4-isomer, two cross-peaks between the N−α-hydrogens and the C2 and C6 were observed (Figure , structure II ). In structure II , the C6 was assigned by the cross-peaks with H5 and with the ortho -hydrogens of the aryl group, while the C4 was assigned by its characteristic quartet due to the two-bond coupling with the CF 3 group ( 2 J CF ≈ 35 Hz).…”

“…This reaction furnished a mixture of the unreacted enone 1a and the intermediate I (entry 1, Table ). In a previous study, a structure similar to the intermediate I was obtained as a single product, in 98% yield, by performing the reaction using sodium carbonate instead of sodium hydroxide solution, at 0 °C for 2.2 h …”

Synthesis of Methylene-Bridged Trifluoromethyl Azoles Using 5-(1,2,3-Triazol-1-yl)enones

“…33 It is well known that when unsymmetric S-methyl isothioureas are cyclocondensed with 4-alkoxy enones, 3-substituted dihydropyrimidin-4-ol derivatives are furnished exclusively. 46,47 However, in this work two different compounds were obtained, depending on the reaction conditions.…”

Unsaturated polyfluoroalkyl ketones in the synthesis of nitrogen-bearing heterocycles

“…The reactions of b-alkoxyvinyl(polyhaloalkyl)ketones with methylthiopseudourea or 1,2-dimethylisothiourea result in formation of di-or tetrahydropyrimidines depending on reaction conditions and structure of initial enone. 84,85 For instance, the treatment of triuoro-38a or trichloromethylketone 39a with 1,2-dimethylisothiourea generated from its salt by 1 M NaOH at room temperature furnishes the tetrahydropyrimidines 40a and 41a correspondingly (Scheme 17). 84 When reaction mixture of enone 39a with the same nucleophile is heated, the elimination of CCl 3 group occurs to form pyrimidinone 43a in almost quantitative yield.…”

“…84,85 For instance, the treatment of triuoro-38a or trichloromethylketone 39a with 1,2-dimethylisothiourea generated from its salt by 1 M NaOH at room temperature furnishes the tetrahydropyrimidines 40a and 41a correspondingly (Scheme 17). 84 When reaction mixture of enone 39a with the same nucleophile is heated, the elimination of CCl 3 group occurs to form pyrimidinone 43a in almost quantitative yield. In contrast with ketones 38a and 39a, their methyl-substituted analogues 38b and 39b under the same conditions give dihydropyrimidines 42b and 43b correspondingly.…”