Pyrimidine-2 -thiones reduction

Cycloaddition and cyclization routes were used to access certain 1,3-diazines. The 4+2 cycloaddition reaction of 4-(N-allyl-N-aryl)amino-l,3-diaza-l,3-butadienes with vinyl-, isopropenyl-, and chloroketene led to pyrimidinone-fused pyrimidinones <97T13841>. Cis-cyclopenta[d]pyrimidines were derived from cis-2-amino-l-cyclopentanecarboxylates by cyclization with KOCN and KSCN <97JHC1211>. 2-Thioxopyrido[3, 2 4,5]thieno[3,2-r/]pyrimidin-4(3//)-ones 19 were prepared by cyclocondensation of 2-carbethoxy-3-amino-4-phenyl-6-substituted-thieno[2,3-/)]pyridines and isothiocyanates <97JHC937>. Thiazolyl-benzimidazoles derived from 2-cyanomethyl-l//-benzimidazole and 2,3-dihydrothiazole-2-(3//)-thiones were cyclized to the corresponding thiazolo[4,5-r/]pyrimidines <97PHA346>. Reductive cyclization of 6-cyanomethyl-5-nitropyrimidines afforded 7-alkyl-5//-pyrrolo[3,2-r/]pyrimidines and 6-amino-7,7-dialkyl-7//-pyrrolo[3,2-rf]pyrimidines <97T391>. 7-Methyl-5-alkyl-2-vinyl-pyrazolo[3,4-r/]pyrimidine-4,6(5//,7//)-diones arose from cyclization and alkylation of... 

Pyrimidine-4(3H)-thione, 6-methoxy-5-nitro-reduction, 3, 88 Pyrimidinethiones acidic pK, 3, 60 S-acylation, 3, 95 N-alkylated synthesis, 3, 139 aminolysis, 3, 94 desulfurization, 3, 93 electrophilic reactions, 3, 69 hydrolysis, 3, 94 oxidation, 3, 94, 138 pyrimidinone synthesis from, 3, 133 reactions... 

The experimental observations on the mechanism(s) of electroreduction of 2-thio-pyrimidines have been interpreted on the basis of their electronic structures as calculated with the aid of the CNDO/2 and Huckel procedures l42). The energies of LUMO (lowest unoccupied molecular orbitals), calculated for pyrimidine and its 2-oxo-and 2-thioderivatives, were compared with the reduction half-wave potentials (Table V). These show that the presence of a carbonyl or thione substituent at C2 enhances the electron acceptor properties of the molecule, which are correlated with formation of a dimer susceptible to photooxidation. 

Pyrimidin-2(l//)-ones (85 X = O) and -thiones (85 X = S) on reduction with sodium borohydride afford mixtures of lH-3,4- (86) and l//-3,6-dihydropyrimidinones (87), the product ratios depending on the acidity of the medium, and some further reduction to the fully reduced pyrimidinones may also occur. Similar results are obtained with LAH as the reductant, although l-arylpyrimidine-2-thiones mainly form the corresponding 3,6-dihydropyridine-2-thiones (88), especially if a hydroxy or methoxy group occupies an ortho position in the aryl substituent. This suggests that the group may complex with the reagent and facilitate an intramolecular hydride transfer reaction. L-Selectride reduces N-benzyl-... 

The best preparative method for mercaptopyrimidines varies from position to position from thioureas and their equivalents. Thiones in any of the electrophilic positions are prepared by thiolysis of halo-pyrimidines, or commonly by thiation of pyrimidinones using phosphorus pentasulfide or, more recently, the superior Lawesson reagent 2,4-bis-/ -methoxyphenyl-l,3,2,4-dithiadiphosphetane 2,4-disulfide. Thiolysis in the 5-position requires a metal sulfide and a 5-bromide under vigorous conditions. Alternatively, pyrimidines substituted with strongly electron-donating substituents may be sulfonated, for example, by chlorosulfonic acid, in the 5-position with subsequent reduction to thiol. 

Dihydrothiophens are readily available by Birch reduction of thiophens, and they may be alkylated adjacent to activating substituents. Subsequent removal of sulphur provides a useful route to substituted butadienes. Finally in this Section the preparation of l,2-dithiolo[3,4-with carbon disulphide in the presence of sodium hydroxide and dimethyl sulphate gives good yields of the expected pyrimido[4,5-6]quinolines (210). However, upon acid work-up in the absence of Me2S04 the reaction follows a different course. The amino-function is lost and the sulphur heterocycles (209) are obtained. 

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