Dihydro-s-triazines

The one-pot, three-component synthesis of a 20-membered dihydrotri-azine hbrary was also dramatically accelerated through the use of microwave irradiation [79]. Heating a subset of substituted anilines, cyanoguanidine and acetone in the presence of concentrated hydrochloric acid for 35 min at 90 °C in a single-mode microwave reactor gave the corresponding 2,2-dimethyl-1,2-dihydro-s-triazine hydrochloride 51 in comparable yield to conventional conductive heating methods but in a much shorter reaction time and increased purity (Scheme 21). 

The condensation of 2-naphthylamine hydrochloride, cyanoguanidine and acetone yields, in addition to the expected dihydro-s-triazine, l-(2-naphthyl)biguanide and 3-guanidino-l-methylbenzo[f]quinazoline (554). 

Base-catalyzed additions of HCN to s-triazine (1) give 2-cyano-l,2-dihydro-s-triazine (9). Its H-NMR spectrum shows that the hydrogen on the nitrogen is equilibrating rapidly between the 1- and 3- positions. When 9 is heated to 65°C it melts and eliminates HCN (72UP1). 

Two Russian papers359,360 have described the synthesis and addition of acetylenic esters to dihydro-s-triazines. The triphenyl derivative 281 on heating with DEAD in ether for 3 hours gave 80% of286, presumably via 285. The diphenyl propyl derivative (282) added Michael fashion to... 

Dihydro-s triazine-2,4 diol (called 2.4-Dioxo-hexahydro-1.3.5-triazin in Ger)... 

A review by Modest summarizes methods developed for use of the reagent for the synthesis of aromatic triazines (2)° and of 4,6-diamino-l-aryl-l,2-dihydro-s-triazines (4). ... 

The use of antifolates in the treatment of coccidiosis in domestic animals has also been established. It has been found that compounds derived from 2,4-diamino-pyrimidines and 2,2-dialkyl-l-aryl-4,6-diamino-l,2-dihydro-s-triazines exhibit promising anticoccidial activity. The noteworthy compounds of this class were found to be pyrimethamine (33), diaverdine (35) and ormetoprim (36) [59]. The metabolites 31a,b of proguanil and chlorproguanil also exhibit marked activity against coccidiosis [60]. 

The guanidine analogues, in general, are not found to be active unless and imtil they get cyclized metabolically to a dihydro-s-triazine analogue having a close resemblance either to the pteridine moiety of folic acid or pyrimethamine as shown below ... 

Scheme 21 One-pot three-component synthesis of dihydro-s-triazines...

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