Pyrimidine-2 lH -thiones

Preparation of three different types of N-substituted stable dihydropyrimidines allows for an excellent comparative study of the spectral properties of these compounds, enabling unambiguous structural determinations of less stable congeners. 

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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-... 

In the addition reactions of organometallic regents to pyrimidin-2-(lH)-one/thione 321, Giignard reagents added regioselectively at C-6... 

The reaction of dihydropyrimidine-2(lH)-thione (propylenethiourea) 1 with a-halocarboxylic acids gives only the bicyclic thiazolo[3,2-a]pyrimidine. The most convenient procedme for the synthesis of 3,4-dihydropyrimidine-2(l//)-thiones (known as the Biginelli reaction) is based on one-pot three-component condensation of aldehydes with P-keto esters and thiomea. Thiazolopyrimidine derivatives (3, Scheme 1) were obtained by a simple one-pot condensation reaction of 1 and 2-bromopropionic acid (2, R3 = H, bromoacetic acid (2, R3 = H, CH3) imder microwave irradiation and conventional conditions [12, 13]. 

Alkylation of l-methyltetrahydropyrimidine-2(lH)-thione (N-methylpropylenethiourea) with chloro- and bromoacetic acids and their esters gave 8-methyl-3-oxo-2,3,6,7-tetrahydro-5H-[l,3]thiazolo[3,2-a]pyrimidin-8-ium chloride or bromide 38 (Scheme 16). The former is readily hydrolyzed in 95% ethanol to 3-[(3-methylamino)propyl]-l,3-thiazolidine-2,4-dione hydrochloride 39 [40,41],... 

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-... 

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). 

Cyclocondenzation of 2-pyridylacetonitrile and ethoxycarbonyl isothiocyanate in MeCN gave 4-cyano-l-oxo-2,3-dihydro-lH-pyrido[l,2-c]pyrimi-dine-3-thione in 18% yield (08MI2). 6-Endo-trig cyclization of anion, formed from 4-methylpyrimidine by LDA in THF at —78 °C, with methyl 3-propynoate provided 8-methyl-6H-pyrido[2,l-c]pyrimidin-6-one in 47% yield (06TL5063). 

Anthranil amide is also readily cychzed with carbon disulfide in pyridine to l,2,3,4-tetrahydroquinazolin-4-one-2-thione (XXXVII, m.p. 282° C) 159). Using a -amino thiocarbonamide instead of a -amino carbonamide yields condensed l,2,3,4-tetrahydropyrimidine-2,4-dithio-nes. An example is the synthesis of 4,5,6,7-tetrahydro-lH-pyrazolo-[3,4-d]pyrimidine-4,6-dithione (XXXVIII m.p. >26O°C) from 4-thio-carbamoyl-5-aminopyrazole 159). 

Acyl-2,3-dihydro-lH-pyrido[l, 2-c]pyrimidin-4-ones were obtained when 2-vinylpyridine was reacted with acyl isocyanates (75IZV2608), Cyclocondensation of 3-methoxy-2-(2-oxopropyl)piperidine and phenyl isothiocyanate in boiling ethylene dichloride afforded 3-methyl-5-meth-oxy-2-phenyl-2,4a,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidine-l-thione (55JOC136). 

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