4.5- Dihydro-l ,2,4-triazin-6-one

Thioxo-4,5-dihydro-l,2,4-triazin-6-ones (708) are reported to be prepared by treatment of a-(4-thiosemicarbazido)acetates (707) with sodium ethoxide (64CB994) there is, however, some doubt about the structure of these products (68CCC2087). 

SAA1853>, and this can be illustrated, for instance, by the structural elucidation of a palladium(ii) complex with the oxime of (L)-3-acetyl-5-benzyl-l-phenyl-4,5-dihydro-l,2,4-triazin-6-one <2000H(53)1737>. 

N-Alkylation of 4,5-dihydro-l,2,4-triazin-6-ones 180, including optically active compounds, takes place regioselec-tively to form predominantly 1-alkyl derivatives 181. Additional treatment of l,2,4-triazin-6-ones 181 with alkylhalo-genides affords l,4-dialkyM,5-dihydro-l,2,4-triazin-6-ones 182 (Scheme 114) <2000TL671>. 

The solid phase synthesis of 1-substituted 4,5-dihydro-l,2,4-triazin-6-ones from imidate esters and substituted hydrazines has been reported <01TL6455>. The first reported solid phase synthesis of 3-amino-l,2,4-triazin-5(4W)-ones has been described. Reaction of polymer-bound isothiourea with 2,3-diaza-3-pentenedioic anhydride afforded the title compounds in... 

There is one case in which a seven-membered ring has provided the four-atom fragment in this synthetic combination. Reaction of the 1,4-oxazepinone (597) with hydrazine provided 3-(diphenylmethyl)-6-phenyl-4,5-dihydro-l,2,4-triazine (598) (73JOC3466). 

The reaction of a-amino ketones (508d) with thiosemicarbazides (761) affords 3-amino-4,5-dihydro-l,2,4-triazines (762) and the dihydrotriazine-3-thiones (763) (57MI21900). 2,2-Dimethyl-3-dimethylamino-2i/-azirine (764) reacts with benzohydrazides (765 R = Ar) via the open-chain intermediates (766) to give 3-aryl-6-dimethyIamino-2,5-dihydro-l,2,4-triazines (767 R = Ar). With ethyl carbazidate (765 R = OEt) the corresponding triazin-3-one (768) is formed (78HCA2419,78C332). 

The cyclization of a-hydrazinohydrazones (653) with ketones has been used for the synthesis of 4-amino-2,3,4,5-tetrahydro-l,2,4-triazines (654), and their reaction with phosgene affords 4-amino-4,5-dihydro-1,2,4-triazin-3-ones (655) (78HC(33)189, pp. 608, 656). 3-Thioxo-l,2,4-triazine-5,6-dione (657) was obtained when oxamohydrazide (656) reacted with thiophosgene (76ACS(B)7l). 

Recently, the UV spectra of a series of 3-methoxy- and 3-methylthio-2,5-dihydro-l,2,4-triazines have been reported 227,228,231,235 In general, these compounds show only one absorption maximum, in the region 240-270 nm (e 2000-5000). According to Sasaki et al,227,228 the hypsochromic shift in the UV absorptions of the similarly substituted 2,5-dihydro-1,2,4-triazines, relative to that of the 4,5-dihydro-1,2,4-triazines, indicates less extensive conjugation of the former, and confirms the insulation of both double bonds. Interestingly, introduction of a phenyl group in position 6 of 2,5-dihydro-1,2,4-triazines produces a new maximum in the UV spectra, at 300 nm and with medium intensity (e 1200). In addition, a hypsochromic shift of the first absorption band was observed (230-250 nm), with a significant increase in intensity (e 20,000). 

Reaction of 6-amino-5-thioxo-4,5-dihydro-1,2,4-triazin-3(2//)-one (328) with haloacetophenones provides the 7-aryl-2,8-dihydro-3//-[l,4]thiazino[2,3-e]-l,2,4-triazin-3-ones (329) (Equation (40))... 

This ring system is represented by tricyclic ring system 533 (76JHC1249). Reaction of 3-hydrazino[l,2,4]triazin-5-ones 531 with 3-imi-nobutyronitrile afforded 6-methyl- (or phenyl-) 3-[3-methyl-5-aminopyra-zolyl]-2,5-dihydro[l,2,4]triazin-5-ones 532A, which may exist in tautomeric form 532B. Its reaction with diethoxymethyl acetate (DEMA) or ortho-esters afforded the tricyclic compounds 533. 

The addition of methoxide ion to 3-methylthio-l,2,4-triazine-5-ones (78) leading to (98) and then to (99) is reported by Piskala (75CCC2340). Hydrazine adds to the C=0 double bond of 3-thioxo-l,6-dihydro-l,2,4-triazin-5-ones (100) (70BSF1606). 

Treatment of l-benzoyl-6-methyl-l,6-dihydro-l,2,4-triazine-3,5-dione (126) with bases led to the 5-phenyl-1,2,4-triazolin-3-one (127) (03JA386). 

Reaction of l,2,4-triazin-5-ones (151, 152) or 5-methoxy-l,2,4-triazines (156) with Grignard reagents afford, depending on the structure of the 1,2,4-triazine used, 1,2,4-triazines (153), 3,4-dihydro- (154), or 1,6-dihydro-1,2,4-triazin-5-ones (155) (73JHC559). 

Reduction of l,2,4-triazin-3-ones (84) with Raney nickel, zinc and acetic acid, lithium aluminum hydride, sodium borohydride, titanium(III) chloride, p-toluenethiol, hydrogen and a palladium catalyst, or electrochemically, produces 4,5-dihydro-l,2,4-triazin-3-ones (268) (78HC(33)189, p. 246, 80JHC1237), which may be further reduced to 1,4,5,6-tetrahydro-l,2,4-triazin-3-ones (269). l,2,4-Triazin-3-ones (84) with hydriodic acid and phosphorus yielded imidazoles (05LA(339)243). 3-Alkoxy-l,2,4-triazines (126) and sodium borohydride gave the 2,5-dihydro derivatives (270) (80JOC4594). 

Substituted 3-thioxo-l,2,4-triazin-5-ones (76 R4 = H) are stable toward sodium amalgam, but the 4-substituted derivatives (76 R2 = H) are reduced to the 1,6-dihydro compounds (282). Hydrogenation of (76 R2 = H) affords ring-opened products. 3-Methyl-thio-l,2,4-triazin-5-ones (78) are reduced by sodium amalgam to 3-methylthio-3,4-dihydro-... 

Desulfurization of l,6-dihydro-l,2,4-triazine-3,5-dithiones (288) leads either to tetrahydro-l,2,4-triazin-3-ones (289) or to tetrahydro-l,2,4-triazines (290), depending on the conditions (70BSF1606). 

Copper(II) acetate in refluxing methanol has been used to prepare 3-alkyl-5-methyl-6-phenyl-3,4-dihydro-l,2,3-triazin-4-ones 568 from 2-(alkylamino)-4-methyl-5-phenyl-l,2-dihydropyrazol-3-ones 567 (Scheme 256). Alternatively, this conversion may be achieved, albeit in a slow reaction, using airoxygen in the presence of sodium hydro-gencarbonate <2006EJ03021>. 

Reaction of 5,6-diphenyl-l,2,4-triazin-3-one (215) or 5,6-diphenyl-l,2,4-triazine-3-thione (216) with benzene under Friedel-Crafts conditions led to the isolation of 5,5,6-triphenyl-4,5-dihydro-l,2,4-triazin-3-one (217) and -3-thione (218) respectively (76IJC(B)273). Reacting under similar conditions (C6H6/AlCl3) the 6-styryl compounds (219-221) are converted into the corresponding 6-(2,2-diphenylethyl) derivatives, e.g. (222) from (219) (75IJC1098). 

Methyl-l,2,4-triazin-5-one (271) with lithium aluminum hydride formed the 1,2,5,6-tetrahydro-1,2,4-triazine (272), and reduction of the 2,6-dimethyl-l,2,4-triazin-5-one (273) and 4,6-dimethyl-l,2,4-triazin-5-one (274) led to the dimethyl-3,4-dihydro-l,2,4-triazin-5(2//)-ones (275) and (276), respectively (73JHC559). 

Allylthio-l,2,4-triazin-3(2//)-ones (224) can be rearranged by palladium(II) catalysis only 4-allyl-5-thioxo-4,5-dihydro-l,2,4-triazin-3(2//)-ones (225) were obtained, with (in cases in which R = H in (224)) none of the C-6-alkylated products (Equation (24)) <85T5289>. 

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