Quinazoline-thiones

The reaction of 2-isothiocyanato benzonitrile with aryl acetonitrile anions was used to prepare quinazoline thione derivatives 53 <06S3067>. 

Synthesis of 9-substituted tetrahydroazepinopurines as asmarine analogs has been described <03T6493>. In relation to adenosine receptor antagonists, new derivatives of pyrazolo[4,3-c][l,2,4]triazolo[l,5-c]pyrimidines have been synthesized <03IMC1229, 4287>. A one-pot synthesis of l,2,4-triazolo[l,5-c]quinazoline thiones 65, consisting of a domino cyclization of 2-isothiocyanatobenzonitrile 63 with hydrazides 64 has been published <03EJO182>. 

Alkylthio derivatives are frequently made by -alkylation of the corresponding quinazoline-thiones. Arylthio, as well as alkylthio derivatives, can be prepared by nucleophilic substitution of halogenoquinazolines by the corresponding thiolates [Pg.133]

Quinazoline methiodide, 29 Quinazoline 3-oxides, 31 Quinazoline-thiones, 31, 51 4-Quinazolone, 3-alkyl-, 31 Quindolines, 103, 134, 144, 146 Quindoline-11-carboxylic acid, 144 Quinindoline, 135, 144 Quinolines, alkoxy-, reactions of, 311 2-alkyl-, reaction with carbenes, 77 aza-effects in, 318 basicity of, 244, 245, 247, 288, 289... 

The preparation of quinazoline-2(and 4)-thiones follows those of the corresponding pyrimidines (67HC(24-1)270) but there is at least one special primary synthesis for quinazoline-4(3H)-thiones, illustrated by the reaction of o-aminobenzonitrile with thioacetic acid at 110 °C to give 2-methylquinazoline-4(3H)-thione in 90% yield (53JA675). 

The 2- and 4-alkylthioquinazolines are formed by the second or third of the above methods as appropriate. For example, quinazoline-2(l//)-thione and methyl iodide/alkali give the thioether (883) and the 4-thioether is made similarly (62JCS3129) 2,4-dichloroquinazoline and sodium p-chlorothiophenate give 2-chloro-4-p-chlorophenylthio-(884 R = C1) or 2,4-bis-p-chlorophenylthio-quinazoline (884 R = SC6H4C1) according to conditions (48JCS1766). 

Quinazoline-4(3 H) -thione, 2-methy 1-synlhesis, 3, 136 Quinazolinethiones structure, 3, 67 synthesis, 3, 136 Quinazoline-4-thiones aminolysis, 3, 94... 

Pyrimidine-2-thiones (e.g., 206) have been shown to exist as such by comparison of their ultraviolet spectra with those of both alkylated forms.The ultraviolet spectra of pyrimidine-4-thiones are different from those of 4-alkylthiopyrimidines, therefore the former compounds exist as 207 and/or 208, the predominant form not having been determined. Infrared spectral evidence suggests that quinazoline-4-thione exists as 209 and/or 210 and has been used recently to demonstrate the thione formulation for pyrimidine-2- and -4-thione, pyrazine-2-thione, and quinoxaline-2-thione. In view of this work, the report that X-ray crystallographic evidence supports the mer-... 

Fry et al. prepared quaternary salts from 4-methyl- and 4-methyl-thio-quinazoline and found that the same cyanine dyes were obtained by suitable reactions of either salt. An unambiguous synthesis of the 4-methylthio salt (69) from l-methylquinazoline-4-thione (70) proved that both of the salts carried groups on N-1. 

The mesomeric effect of the C=S linkage is very pronounced and is responsible for the facile quaternization of heterocyclic N-alkylated thiones (159) this effect is operative even when such a shift does not increase the aromaticity of the ring. Thione derivatives of pyridazine, benzothiazole, quinazoline, 1,3-thiazine, triazole,and isoindole are examples of compounds which readily form quaternary salts. 

Alkylthio, arylthio, and thioxo. The thioxo group in pyrimidine-2,4-dithione can be displaced by amines, ammonia, and amine acetates, and this amination is specific for the 4-position in pyrimidines and quinazolines. 2-Substitution fails even when a 5-substituent (cf. 134) sterically prevents reaction of a secondary amine at the 4-position. Acid hydrolysis of pyrimidine-2,4-dithione is selective at the 4-position. 2-Amination of 2-thiobarbituric acid and its /S-methyl derivative has been reported. Under more basic conditions, anionization of thioxo compounds decreases the reactivity 2-thiouracil is less reactive toward hot alkali than is the iS-methyl analog. Hydrazine has been reported to replace (95°, 6 hr, 65% 3deld) the 2-thioxo group in 5-hexyl-6-methyl-2-thiouracil. Ortho and para mercapto- or thio- azines are actually in the thione form. ... 

Treatment of pyrimidine-2-thione 193 with AICI3 in PhN02 yielded 2-(4-benzylphenyl)-6-oxo-6,7-dihydro-4//-pyrido[6,l-a]isoquinolin-4-thione (194) (98MI47). Cyclization of l-(2-carboxyethyl)-l,2,3,4-tetrahydroquina-zoline-2,4-dione (195) in PPA afforded l,2,3,5,6,7-hexahydropyrimido[3,2, l-//]quinazoline-l,3,7-trione (196) (97CHE96). 

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). 

Quinazoline-2-thione-4-one (522) and its 3-phenyl derivative coordinate to Ni11 after deprotonation via the S and the NI donor resulting in a square planar complex.1372 The related 2-isopropylquinoline-8-thiolate (523) forms a distorted tetrahedral complex.1 73 For deprotonated 2-thiocarbamyl-thiazoline (HL = (524)) the octahedral complex [NiL(H20)4]+ is favored over the square planar [NiL2] complex.1374... 

Quite similarly, the reaction product obtained from 2-benzylthio-3-phenylquinazolin-4(3H)-thione and hydrazine should be assigned the structure 2-anilino-3-aminoquinazoline-4(3//)-hydrazone instead of the reported 2-hydrazino-3-phenyl quinazoline-4(3//)hydrazone (Scheme III.23) (70IJC1055). 

Hydroxy, thiol, and amino groups in pyrimidine exist in tautomeric equilibria with their oxo, thioxo, and imino forms. An amino group in an electrophilic position exists predominantly as such, and the compound is named as an amine. Pyrimidines with a hydroxy or thiol group in an electrophilic position are dominated by the oxo or thioxo forms and are named as such, or with -one or -thione suffixes, if these are the principal groups. In the benzenoid 5-position, these derivatives are mainly present in the hydroxy, thiol, or amino forms and are named as such. Similar considerations apply to the nomenclature of quinazolines and perimidines <1996CHEC-II(6)93>. 

Quinazoline alkylthio derivatives are frequently made by S-alkylation of the corresponding quinazolinethiones. The conditions required are very mild, and S-alkylation can be performed in the presence of other groups capable of undergoing alkylation. For example, 777-imidazo[4,5-, ]quinazoline-6(777)-thione 209 was converted to the 4-methylthio derivative 210 at room temperature, without any alkylation of the nitrogen atoms of the imidazole ring <1996JME918>. 

Other examples this type of quinazoline synthesis include the formation of the thione analog 752, by displacement of bromine from thiourea 751 <2003ARK(x)434>, and the imino compound 754, which could be formed by heating the guanidine derivative 753 in DMF, without the need for any added base <2005RJ01071>. 

Indolo[2,l-b]quinazoline-12-thione (69) was obtained by cyclodehy-drohalogenation of 2-bromomethyl-3-phenylquinazoline-4(3//)-thione (68) with liquid ammonia (73IJC500) the expected amination product was not isolated. 

Reaction of benzodithiol-3-thione (220) with anthranilamide gave a complex mixture of products from which benzisothiazolo[2,3-u]quinazolin-5 one (221) was isolated (75JHC1077). 

Cyclization of 3-aminoquinazoline-4-thiones (375) with carbon disulfide gave the zwitterionic l,3,4-thiadiazolo[3,2-c]quinazoline (376) (771JC(B)1110]. Synthesis from properly functionalized 1,3,4-thiadiazole precursors was also reported [83JCS(P1)2011], according to which the 2-(2-nitrophenyl)-l,3,4-thiadiazoles (377) were reduced and cyclized to 378. 1,3,4-Thiadiazoloquinazolines were shown to exhibit amebicidal... 

---