Pyrimidine-2 -thiones, 1-aryl

Reactions of iV -alkylated or arylated azinium compounds with nucleophiles proceed more readily than those of the parent, uncation-ized azines, and the ring tends to open. The iV -substituent may bring into play an accelerative effect from the London forces of attraction. Increased displaceability of the substituent in iV -alkyl-azinium compounds has been noted for 2-halopyridinium (87) 1-haloisoquinolinium, 4-halopyrimidinium, 4-methoxypyrid-inium (88), 4-phenoxy- and 4-acetamido-quinazolinium (89), 3-methylthiopyridazinium, and 2-car boxymethylthiopyrimidi-nium salts (90). The latter was prepared in situ from the iV -alkyl-pyrimidine-2-thione. The activation can be effectively transmitted to... 

Treatment of resin-bound iminophosphorane 197 with an excess of solid CO2 and CS2 in a sealed glass tube, and with aryl isocyanates afforded I-OXO-, 1-thioxo- 198, and l-arylimino-l//-pyrido[l,2-c]pyrimidine-3-car-boxylates 199 (OlJMClOll). Reaction of iminophosphorane 200, derived from 2-(2-azidophenyl)pyridine with excess PPh3, yielded 6//-pyrido[l,2-c] quinazoline-6-thione (201). 

Reaction of 2-cyanomethylpyridine with iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)-iV -(4-methylphenyl)carbodiimides, and with (1,1,2,2,2-pentachloro- and l,l-dichloro-2,2,2-trifluoroethyl)isocyanates or A-methoxycarbonyl-l,2,2,2-tetrachloro-, — l-chloro-2,2-trifluoroacetaldehyde imines afforded 3-aryl-4-cyano-l-(4-methylphenyl)imino-3-trifluoromethyl-2,3-dihydro-17/-pyrido[l,2-f]pyrimidines and 4-cyano-3-trichloro-, 4-cyano-3-trifluoro-17/-pyrido[l,2-4pyrimidin-l-ones, respectively <2004CHE47>. Refluxing 2-cyanomethylpyridine and iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)isocyanates in benzene furnished l-aryl-4-cyano-l-trifluoromethyl-l,2-dihydro-3//-pyrido[l,2-4pyrimidin-3-ones. However, when the solution of the isocyanate was added dropwise to the solution of 2-cyanomethylpyridine, and the reaction mixture was then treated with NEt at room temperature, the isomeric 3-aryl-4-cyano-3-trifluoromethyl-2,3-dihydro-l//-pyr-ido[l,2-dpyrimidin-l-ones were obtained. Reaction of l-(acetyl- and benzoylmethylene)-6,7-dimethoxy-l,2,3,4-tetra-hydroisoquinolines with PhCONCS yielded 1-acetyl-, 1 -benzoyl-9,10-dime thoxy-3-pheny 1-6,7-dihydro-2//-pyrimido[6,l- ]isoquinoline-2-thiones <2003SL2369>. 

C-Enamino-imines obtained by photolysis of l//-pyrimidin-2-ones have been treated with carbon disulfide, giving 2//-l,3-thiazine-2-thiones (22) and/or l-aryl-l//-pyrimidine-2-thiones (23) (Scheme 13) [82JCS(P1)2149]. 

Alkylation of l-aryl-4-cyano-l-trifluoromethyl-2,3-dihydro-lH-pyrido [l,2-c]pyrimidine-3-thiones with benzyl bromides, ethyl 2-broroacetate, and 2-chloroacetamides in the presence of K2C03 in DMF at ambient temperature gave 3-[(substituted methyl)thio)]-lH-pyrido[l,2-c]pyrimi-dines in 51-87% yields (07MI1). 

Sukumaran and Rajasakharan [89IJC(B)642] reported that reaction of o-aminocarbonitriles 48 and powdered sodium hydroxide in DMF with alkyl or aryl isothiocyanates gave directly 3-alkyl- or 3-aryl-4-iminothieno [2,3-d]pyrimidine-2-thiones 77a. By altering these reaction conditions slightly, the same authors claimed to isolate thioureas 79a, which were cyclized in boiling pyridine to 4-phenyl- or 4-arylthieno[2,3-d]pyrimidine-2(lH)-thiones 78a via Dimroth-type rearrangement of intermediate 4-... 

Diphenyl-3,5-bis-(arylidene)-thiopyrane-4-one (238), on condensation with thiourea in basic medium, gives thione 239 which reacts with a-halogenoacids to furnish a cyclized product for which the structure 2- f/aryl-5-aryl-9-arylidene-6,8-diphenylthiazolo[3,2-a]thiopyrano[4,3-c/]-pyrimidin-3(2//)-ones (240) was assigned (85MI1) (Scheme 59). The other possible isomeric structure 241 could also represent the cyclized product. 

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 replacement of thioxo by oxo groups through oxidative treatment with hydrogen peroxide has been reported for a number of 4-aryl-8-ary lidene-3,4,5,6,7,8-hexahyd ropy rido[4,3-rf]-pyrimidine-2(l/f )-thiones.511... 

---