Amidines, from triazoles

A combination of the preceding type of synthesis and of cyclization of 4-amino-5-arylazopyrimidine can be seen in the novel procedure of Richter and Taylor. Proceeding from phenylazomalonamide-amidine hydrochloride (180), they actually close both rings in this synthesis. The pyrimidine ring (183) is closed by formamide, the triazole (181) one by oxidative cyclization in the presence of cupric sulfate. Both possible sequences of cyclization were used. The synthetic possibilities of this procedure follow from the combination of the two parts. The synthesis was used for 7-substituted 2-phenyl-l,2,3-triazolo[4,5-d]-pyrimidines (184, 185). An analogous procedure was employed to prepare the 7-amino derivatives (188) from phenylazomalondiamidine (186). 

Azolium iV-amidine 427, readily prepared from salt 426 in the presence of iV-ethyldiisopropylaminc, reacts with phenylisocyanate to afford the corresponding imidazo[l,3- ][l,2,4]triazole 126 in a formal [4+2] cyclocondensation process (Equation 88) <2001JOC8528>. 

Triazoles have also been obtained when the carbon atom adjacent to the activated methylene group carries a nitrogen function (i.e., amides, nitriles, amidines, and imines - ). In many of these cases it is impossible to decide, without N-labeling experiments, whether the third nitrogen of the triazole ring is derived from the toluene-p-sulfonyl azide or from the activated methylene compound. With amides, amidines, and nitriles, the first possibility seems more reasonable, but with imines, the third nitrogen is that of the imino group (Scheme... 

Hydroxythiazolo[3,2-fi][l,2,4]triazoles (176, R = OH) are also available by this route. Treating 167 with methyl chloroformate (sodium hydroxide) and subsequently with sodium methoxide yields 176 (R = OH) (71GEP1942015 72GEP2032173, 72USP3682943). Thiazolo[3,2-fi][l,2,4] triazoles are also available from 2-aminothiazoles via amidines 178. Lead tetra-acetate dehydrogenation of 178 leads to 179 (94MI1). 

The resulting triazoles can be N-alkylated by treatment with alkyl halides (0.25 mol/L, 30 equiv., DMF, NaOH), but mixtures of the 1-alkylated and 2-alkylated triazoles are obtained [255]. 1,2,4-Triazoles have also been prepared from N-amino-amidines (amidohydrazones Entry 4, Table 15.20), which were prepared from resin-bound thioamides by S-alkylation with methyl triflate followed by treatment with hydrazine [256]. 1,2,4-Tri azoles undergo Michael addition to polystyrene-bound a-acetamido acrylates to yield triazole-derived a-amino acids (Entry 7, Table 15.20). Benzotriazoles have been N-arylated on insoluble supports by treatment with aryl-boronic acids in the presence of catalytic amounts of copper salts (Entry 8, Table... 

The direct synthesis of aryl- or alkyl nitriles from cyanide and organohalide precursors is revered in synthetic chemistry, as the nitriles represent a flexible functionality that can easily be converted into (for example) carboxylic acids, esters, amides, amidines, amines and various hetero cycles [67], such as thiazoles, oxazolidones, triazoles and tetrazoles [68]. The tetrazole group... 

Another curiois the rearrangement followed by cycli-zation of the azide derived from the dichloride of benzophenone (reaction 97). An example of ring opening of a triazole leading to an amidine is reaction (98)... 

Reaction of 7V-(phenylsulfonyl)benzhydrazidoyl chloride, which fails to yield a 1,3-dipole, with N-substituted benzamidines is postulated to proceed via an intermediate formed by nucleophilic attack of the hydrazidoyl carbon by the more basic imino nitrogen of the amidine. Intramolecular cyclization of the intermediate yields a triazoline loss of amino or phenyl-sulfonyl moieties from the latter leads to triazoles as final reaction products (Scheme 24A) (77BCJ2969). 

Acyltriazolium salts 522, generated in situ from amidines 294, are transformed to 3-substituted 1,2,4-triazoles 523 on heating in nitromethane or acetonitrile (69JPR477, 69JPR646). In this case, the presence of alkali... 

Various synthetic protocols were available for the preparation of 1,2,4-triazoles and derivatives thereof Efhcient synthesis of 3,4,5-tri-substituted 1,2,4-triazoles 171 was accompHshed from the reaction of guanidines 169 with 2,2,2-tri-chloroethylimidates 170 in PEG-400 (14TL177). 3,5-Diaryl-l,2,4-triazoles 173 were synthesized from a domino nucleophilic substitution/ oxidative cycfr-zation sequence from 2 equivalents of amidines 172 with copper catalyst, sodium bicarbonate as base, 1,10-phenanthroline as an additive, and K3[Fe(CN)6]/air as the oxidant (14T1635). Sulfur-substituted 1,2,4-triazoles... 

Reactions of Cyano- and Carboxy-thiophens.—-Amidines and imino-ethers as well as triazoles and tetrazines have been prepared from cyano-thiophens. The modified Lossen rearrangement of sodium JVA -dihydroxythiophen-2,3-di-carboxamide with benzenesulphonyl chloride furnished a mixture of (176) and (177) in 54% yield in a 1 3 ratio. Azo dyes have been prepared by diazotiza-tion of A -(4 -aminophenyl)thiophen-2-carboxamides. 2-Thienylthiocarbonyl... 

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