1.3.5- Triazines from thioureas

The chemistry leading to the formation of s-triazines from thioureas has been of considerable interest historically, and is well summarized in a monograph by Smolin and Rapoport249 thus the newer or less common aspects of these reactions will be dealt with here. 

A useful preparation of, s-triazines from thioureas which has received scant attention in the literature is to be found in the work of Burke,255 who discovered that treatment of thiourea with aldehydes in the presence of amines leads to hexahydro-s-triazinethiones (119) in high yields. The starting thiourea may be 1,3-disubstituted, and the amines... 

Another type of reaction leading to s-triazines from thioureas is that of Johnson and Menge,268 who reported that the imidothiocarbonate 129, when treated with 2-ethyl-2-thiopseudourea, gave the triazine... 

A new synthesis of 6-arylamino-2-heteroarylimino-l,2-dihydro-l,3,5-triazines from 2,4-bis-(heteroarylimino)-l,3-diazetidines and amidines has been developed by Molina et al. The formation of the triazines was explained as an initial addition of the imino nitrogen of the amidine to the exocyclic C=N bond, followed by formation of an open chain intermediate. This intermediate cyclized, followed by elimination of 4-amino-6-methyl-3-methylthio-l,2,4-triazin-5(47/)-one to give the triazine product (Scheme 62) <87S150>. 1,3,5-Triazines (207) and (208) have been prepared from 2-acylimino-l,3-thiazetidines (204) by treatment with iso thioureas or guanidines respectively (Scheme 63) <91JHC177>. 

Fused 1,3,5-triazine systems can also be prepared from urea or thiourea derivatives. The syntheses of (90 equation 47) (74JHC199) and (91 equation 48) (76JHC589) illustrate the method. 

The mercapto group can also be formed via the isothiouronium salt (Andriska et al., 1962b Kniisli et al., 1962). With thiourea 2-chloro-4,6-bis(alkylamino)-5-triazines give isothiouronium salt in a practically quantitative yield this is then decomposed by alkali to the corresponding mercapto compound and dicyano diamide. From this, the 2-mercapto-4,6-bis(alkylamino)-s-triazinc derivative is obtained with a methylating agent. The reaction scheme is as follows ... 

Syntheses of this type are from urea, thiourea, and amidine and guanidine derivatives. Ureas give tetrahydro-l,3,5-triazin-2-ones on reaction with a primary amine (1 equiv.) and aqueous formaldehyde (2-30 equiv.). In general, alkyl and aryl amines, unsaturated amines, amino alcohols, and a-amino esters form triazinone derivatives (Equation (43)). Methyl and benzyl have proven to be the most useful urea substituents with respect to high yields and product solubility. N,N -Dicyclohexyl- and A,A -diphenyl-urea gave poor yields of triazinone <90TL2109>. 

The most common method for the preparation of thioureas is, however, based on the reaction of isothiocyanates with amines, and, not unexpectedly, the majority of papers deal with this particular reaction. 6-2 1 Among the N-substituent groups thus introduced into thiourea are 3-cyclo-pentenyl, 1-adamantyl, furfuryl, diphenylphosphinoyl, diphenyl-phosphinothioyl, AW-9,10-diacetyldihydro-2-phena2inyl, and variously substituted aryls. - If the isothiocyanate or the amine contains other reactive groups, cyclization to heterocyclic compounds containing the thiourea grouping may occur, either spontaneously or promoted by external influence, as recently demonstrated in the synthesis of thiones derived from imidazoline, pyrimidine, - and j-triazine. - ... 

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