Pyrimidine-2-thiones, reaction with

Thiadiazinotriazolopyrimidines can be prepared in several ways from the hydrazine-substituted thiadiazino-pyrimidine 186. Reaction with carbon disulfide gives the thione 187 reaction with either anhydrides or orthoformates with sulfuric acid gives the substituted triazoles 188, and reaction with cyanogen iodide gives the aminotriazole 189 (Scheme 47) <2004HC0335>. 

A new synthetic route for functionalized polyhydroxyalkyl-pyrimidines starting from unprotected aldoses and based on montmorillonite K-10 catalysis and solvent-free microwave irradiation conditions, has been reported by Yadav et al,m Thus, reaction of D-glucose and D-xylose with semicarbazide or thiosemicarbazide (186) in the presence of montmorillonite K-10, under microwave irradiation, proceeded via domino cycloisomerization, dehydrazination, and dehydration of the intermediate semi- or thiosemicarbazones (187) to afford l,3-oxazin-2-ones or l,3-oxazine-2-thiones (188) in one single step and in yields between 79% and 85% (Scheme 34). Other mineral catalysts tested, such as silica gel and basic alumina, were far less effective for this transformation and only silica gel was active at all, giving low yields (15-28%) of compounds 188a-d. The l,3-oxazin-2-ones(thiones) thus synthesized were subsequently converted into the target pyrimidines by reaction with aromatic... 

Other examples of CN/CC replacement are observed in reactions of l-phenyl-pyrimidin-2(l//)-one with active methylene compounds, such as diethyl malonate and benzoylacetate, giving in good yield 2-oxo-l,2-dihydro-3-pyridinecarboxylate and 3-benzoylpyridin-2(l H)-one, respectively (84CPB2942, 87H2223) (Scheme 8). In a similar way 4,6-dimethyl-1-phenylpyrimidin-2( 1 //)-one, 4,6-dimethyl-1 -phenylpyrimidine-2( 1 //)-thione and 4,6-dimethyl-1 -phenyl-2-phenylimino-1,2-dihydropyrimidine yield with malonitrile 2-amino-4,6-dimethyl-3-pyridinecarbonitrile. In a similar way 2,3-diarylpyrimidin-4(3//)-thiones give with malonitrile CN/CC replacement (84H763) (Scheme 8). The reaction takes a similar course as described in Scheme 7. 

Surprisingly, only one example of the synthesis of thieno[3,4-,7 pyrimidines has been described starting from a pyrimidine ring. In CHEC-II(1996) <1996CHEC-II(7)229>, substituted 5-cyanouracils, upon reaction with elemental sulfur, led to the formation of compounds in this class. Now the use of a 5-cyanopyrimidino-2-thione 419 under similar conditions (Equation 156) leads to the thienopyrimidine 420 <1997HC0151>. 

Formation of l,2,4-triazolo[l,5-c]pyrimidine-5(6//)-thiones or their 5(6//)-ones by the reaction of l,4,6-triaminopyrimidine-2(l//)-thiones (468) with the Vilsmeier reagent has been found to be dependent on the temperature. Thus, treatment of 468 with phosphoryl chloride and DMF at 0-5°C afforded mainly the thiadiazolopyrimidinium chloride 470 in addition to the thione 471, but at 25°C a mixture of 471 and 7-formamido-l,2,... 

Pyrimido[4,5-d]pyrimidine-4-thiones are also formed by reaction of pyrimido[4,5-d]-pyrimidin-4-ones with phosphorus pentasulfide. Methylation of these thiones with dimethyl sulfate or methyl iodide gives the corresponding methylthio derivatives (60JA5711). 5-Amino-l,3-dimethyl-7-methylthiopyrimido[4,5-d]pyrimidine-2,4(l//,3iy,)-dione (121) undergoes... 

Reaction of 4-cyano-l -oxo-2,3-dihydro-l H-pyrido [1,2-c] pyrimidine-3-thione 72 with halogeno ketones 73 afforded tricyclic derivatives 74 (08MI2). 

The 3-phenylthieno[2,3-d]pyrimidine-2,4-diones 3b and the corresponding -4-one-2-thiones 4b were converted into the respective 2-allyloxy 139a and 2-allylthio 139b derivatives by reaction with allyl chloride in base (89KGS347). 

Heating compound 299 with phosphorus pentasulfide in a mixture of dioxane and pyridine gave 7-(2,3,5-tri-0-benzoyI-/3-D-ribofuranosyl) thieno[3,4-d]pyrimidin-4(3//)-thione 374, in 49% yield. Thione 375, obtained by debenzoylating compound 374, was converted into the 4-methyl-thio-7-/3-D-ribofuranosylthieno[3,4-d]pyrimidine 376 by reaction with excess methyl iodide in 0.1 N aqueous sodium hydroxide. Substitution of the... 

The reaction with ethyl chloroformate or CSC12 gave l,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-2,4-dione <83JAP5802950, 84JAP5903479) and the corresponding 2-thione (267) <81JAP(K)81164189),... 

The Michael reaction of thione 129 with acrylonitrile affords pyrimidine 130, which, however, does not undergo cyclization. After oxidation of pyrimidine 130 to sulfone 131, the acidity of the methylene fragment becomes sufficiently high to allow cyclization of the latter to give thienopyrimidine 132 (1990CCC1049, 1993P26). 

Thongh different bonds are made, it is useful to include here the enaminothioimidate shown below for the synthesis of pyrimidin-2-ones and -thiones, by reaction with isocyanates and isothiocyanates, respectively, proceeding via a cycloaddition between the azadiene and the imine unit of the -N=C=S, then loss of dimethylamine to aromatise. ... 

A useful conversion of a nucleoside 2,6-dithione into a 6-methylamino-adenosine via oxidation with dimethyldioxirane, illustrates several instructive points. The presumed intermediates are sulfinic acids the 2-sulfinic acid loses sulfur dioxide to leave hydrogen at C-2, and nucleophilic displacement of the 6-sulfinic acid (or possibly the sulfonic acid after further oxidation) introduces the amino group. Similar reactions can be carried out on pyrimidine thiones. The scheme shows intermediates derived from a disulfinic acid - it is not clear in what order oxidations/loss of sulfur dioxide/displacements take place. 

Structures comprising One Five-Membered and One Six—Membered Ring (5,6). - Thiazolon.2-al-. r3,4-al-, and 5,4-dlpyrimidines tC NS-C N ]. The reaction of 2-amino-2-thiazoline or thiazolidine with EtOOCCHRCOOEt/Na or R1R2NCH(C00Et)2[R1,R2=various] affords (252 R=alkyl,NR1R2 R3, R = H,bond)285 288. Other methods utilised include the preparation of thiazolo[3,2-a]pyrimidines by reaction of tetrahydropyrimidine-2-thione with broraoketones and... 

The Wittig-type reactions of iminophosphoranes with isocyanates and related compounds have also been extensively used in heterocyclic synthesis. Examples include the preparations of the mesoionic [l,3,4]thiadiazolo[2,3-c][l,2,4]triazines (210) from (209), 0 bicyclic guanidines, e.g. (212), from (211), naphthypyridines (215), (216), and (217) from (213) and (214), 2 pyrido[l,2-f]pyrimido-[4,5-d)pyrimidines (218), 7H-pyrido-[4,3-c]- (219) and 10H-pyrido[3,4-b]- (220) carbazoles, tricyclic fused 2,4-diimino-l,3-diazetidines (222) from the bisiminophosphorane (221), benzotriazepines (225) from (223) and (224), 6 and mesoionic thiazolo-[2,3-b]-1,3,4-thiadiazoles (227) and N,N-bisheteroarylamines from the iminophosphorane (226), derived from 3-amino-4-phenylthiazole-2(3H)-thione. The carbodiimides (229), prepared from the iminophosphorane (228), can be converted into quinolines or a-carboline derivatives depending on the nature of the isocyanate used in the reaction with (228) and the reactions of iminophosphoranes (230) and (231) with aryl and styryl isocyanates provide one-pot syntheses of quinoline, a-carboline, and quinindoline derivatives. 9... 

Treatment of 2-imino-3-phenyl-4-amino-(5-amido)-4-thiazoline with isocyanates or isothiocyanates yields the expected product (139) resulting from attack of the exocyclic nitrogen on the electrophilic center (276). Since 139 may be acetylated to thiazolo[4,5-d]pyrimidine-7-ones or 7-thiones (140). this reaction provides a route to condensed he erocycles (Scheme 92). 

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