Grignard reagents, reaction with 1.2.4- triazines

A considerable number of studies have been made of the reactions of various 1,2,4-triazine derivatives with Grignard reagents. 3,5,6-Triphenyl-l,2,4-triazine (147) with phenylmag-nesium bromide is reported to give 2,4,6-triphenyl-l,3,5-triazine (148) and 2,4,4,5-tetraphenyl-4//-imidazole (149) (71JPR699). 

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). 

The complex triazine (60) is alkylated to give (61) on reaction with Grignard reagents. In their reactions " with RMgX, compounds (62) undergo reductive alkylation to (63), whilst (64) undergoes overall displacement of CN by R. 

Reaction of l,2,4-triazin-3-ones (84) with Grignard reagents affords mainly 4,5-dihydro-l,2,4-triazin-3-ones (150), but the isolation of 1,2,4-triazines or imidazole derivatives has also been reported <78HC(33)189, p. 247). 

Yamanaka has used the reaction of Grignard reagents with 3,6-disub-stituted 1,2,4-triazines 259 to prepare 5-aryl-1,2,4-triazines 261 via oxidation of the intermediate 2,5-dihydrotriazines 260 (85H28O7). 

The synthesis of 1,2,4-triazines 3 by reaction of 1,2,4-triazin-3(2//)-ones 1334 or 1,2,4-tri-azin-5(2//)-ones 2335 with Grignard reagents in an addition/elimination sequence has also been reported. 

The reaction of l-azido-3-chloropropane with Grignard reagents, followed by breakup of the Mg-triazene complex on Dowex resin, affords l-alkyl-3-(3-chloropropyl)triazenes which on concentration undergo cyclization to l-alkyl-1,4,5,6-tetrahydro-l,2,3-triazines 30a-d isopropylamine is added to neuttalize any HCl (Equation 104) <1997JOC8660>. 

Reaction of 3-chloro-5,6-diphenyl-l,2,4-triazine with phenylmagnesium bromide has been found to result in a rather complex mixture of 12 products ), including tetraphenylimidazole (169) and triphenylimidazolone 172. 2,5-Dihydro-1,2,4-triazines 168 and 171, resulting from the addition of the Grignard reagent at C-5 of 3,5,6-triphenyl-l,2,4-triazine 167 and 5,6-diphenyl-l,2,4-triazin-3-one 170, are postulated as the key intermedi-... 

Another method to introduce a substituent into the 1,2,4-triazine system is vicarious nucleophilic substitution. Here, a carbanion with a leaving group at the carbanionic center reacts with a 1,2,4-triazine replacing protons in the 5-, 3- and 6-position with the carbanionic moiety. The reactivity of the various positions decreases in the order 5 > 3 > 6. This reactivity differs from that toward Grignard reagents. Thus, substitution of the 5-position occurs in the 1,2,4-triazine to afford 15 which undergoes elimination to 16 followed by protonation to yield 17 275,276 Carbanions of the following compounds were used in this reaction nitrones, chloromethyl phenyl sulfones, chloromethanesulfonamides and acetonitriles.274-378... 

The reactions studied are Addition of ammonia to 1,2,4-triazines and oxidation of the amino-dihydro compounds with potassium permanganate to amino-1,2,4-triazines (Scheme 15) addition of Grignard reagents or other carbanions to 1,2,4-triazines and oxidation of the dihydro adducts with potassium permanganate or potassium hexacyanoferrate(III) (Scheme 17) and addition of... 

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