Imidazo -1,2,4-triazoles

However, there are differences between o-phenylenediamine and 4,5-diaminopyrazoles in the synthesis of [5.5] systems. For example, the formation of pyrazolo[3,4-d]-[l,2,3]triazole (550) is similar to that of benzotriazole, but all attempts to extend the synthesis of benzimidazoles to the preparation of the imidazo[4,5-c]pyrazole system (551) have failed (78TH40400). 

Several interesting 1,2,4-triazole fused-ring systems have been reported. A facile synthesis of 3,5-dihydro-677-imidazo[l,2-fc]-l,2,4-triazol-6-ones 162 was obtained by an iminophosphorane-mediated annulation <06EJ04170>. 8-Trifluoromethyl-l,2,4-triazolo[4,3- >]pyridazines 163 has been prepared from 4-trifluoromethyl-4,5-dihydropyridazin-3-one... 

Several approaches to the 1,2,3-triazole core have been published in 2000. Iodobenzene diacetate-mediated oxidation of hydrazones 152 led to fused 1,2,3-triazoloheterocycles 153 <00SC417>. Treatment of oxazolone 154 with iso-pentyl nitrite in the presence of acetic acid gave 1,2,3-triazole 155, a precursor to 3-(W-l,2,3-triazolyl)-substituted a,P-unsaturated a amino acid derivatives <00SC2863>. Aroyl-substituted ketene aminals 156 reacted with aryl azides to provide polysubstituted 1,23-triazoles 157 <00HC387>. 2-Aryl-2T/,4/f-imidazo[43-d][l,2,3]triazoles 159 were prepared from the reaction of triethyl AM-ethyl-2-methyl-4-nitro-l//-imidazol-5-yl phosphoramidate (158) with aryl isocyanates <00TL9889>. 

NNN/ 4-methyl-3-phenyl-2-phenylcarbamoyloxy-3//,4//-imidazo[l,Z-b [1,2,4]triazole-3a-carboxylic acid ethyl ester 125 and 4,3a-dimethyl-3-phenyl-2-phenylcarbamoyloxy-3//,4//-imidazo[l,2-A [l,2,4]triazole-6-carboxylic acid methyl ester 126 (Table 27) <2001JOC8528>. 

Imidazo[l,5- ][triazole]-2,5-dithione 234 reacts with methyl iodide to give the di- -methyl derivative 116 (Scheme 17) <1998SL786>. 

The synthesis of ethyl ester derivatives of imidazo[5,l-4][l,2,4]triazole-3-carboxylic acid 64 has been reported (Scheme 25) <1999CHE1349>. Starting from the known substituted 5-diazoimidazoles 276, their coupling with malonic acid derivatives afforded the azo compounds 277, which on treatment with triethylamine in DMF, upon prolonged heating time, gave products 64 in moderate yield. 

The reaction of 2-amino-guanidine-1 -acetic acid hydroiodide 331 with carbon disulfide, heating the substrates in DMF at 130-140 °C for 12 h, produces compound 332 in 76% yield. This compound was subjected to cyclization reaction with acetic anhydride to give 6,7-dihydro-5-oxo-imidazo[2,l-f][l,2,4]triazole 102 in 76% yield (Scheme 32) <1998MI1>. 

Treatment of hydrazonoyl bromide 355 with 5-amino-l//-l,2,4-triazole furnishes imidazo[l,2-3][l,2,4]triazole derivative 357, via intermediate 356 (Equation 68) <1997HAC129>. 

The reaction of phenylazoalkenes 424 with an excess of potassium thiocyanate in acetic acid produces the cycloadducts 425 that undergo further [3+2]-cycloaddition reaction with thiocyanic acid at the azomethine imine function giving rise to the bicyclic product imidazo[l,5-3][triazole]-2,5-dithiones 41 (Equation 87) <1998SL786>. 

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>. 

When benzyl 1-ureidoethylidene hydrazones 463 are treated with triphenylphosphine, the obtained products are 7/7-imidazo [ 1,2 +] [ 1,2,4]triazoles 464 (Equation 106) <1996JHC1877, 1997JHC71>. 

The reaction of 2-amino-l,3,4-thiadiazole 470 and 3-amino-l,2,4-triazole 472 with benzaldehyde and fe/V-butylisoni-trile gives imidazo[2,l-A [l,3,4]thiadiazoles 471 and imidazo[l,2- ][l,2,4]triazoles 473, respectively, in a one-pot process (Equation 110) <1998AG(E)2234>. 

The aroyl-substituted heterocyclic ketene aminals 482 react with 4-chlorophenyl azide to give polysubstituted 1,2,3-triazoles 483 and imidazo[ 1. Z-r 1.2,4]triazoles 39 (Equation 112) <2000HAC387>. Polysubstituted 1,2,4-triazoles are formed by the nucleophilic attack of the ct-carbon of the azide. Then, through the cyclocondensation and aromatization sequences, the fused heterocycles resulted by a 1,3-dipolar addition at first, and then through a Dimroth rearrangement and deamination of chloroaniline <1992JOC184>. 

The treatment of arylglyoxylhydroximoyl chlorides with 2 equiv of 3-amino-277-[l,2,4]-triazole 107 in the presence of triethylamine produces a mixture of 3-aroyl-[l,2,4]triazolo[4,3-6][l,2,4]triazole 108 and 5-aryl-6-nitroso-17/-imidazo-[l,5-d[l,2,4]triazole 109 (Equation 28) <1984JHC1029>. 

Compound 185 can also be obtained by direct bromination of the corresponding thiazolo[3,2-ft][l,2,4]triazole (Bt2, acetie acid) (91AP49). Bromination at C-5 can also be affected by bromine/NBS in chloroform (72YZ935). Thiocyanation, which was possible in the imidazo[2,l-b]thia-zole and -[l,3,4]thiadiazole series (see Sections VI,B,l,a and VII,B,l) failed (72YZ935). 

Generally, azolo-triazenes prepared from pyrazoles and triazoles are less toxic and more stable than the corresponding imidazo derivatives, probably because of the weaker basicity of the ring (69JMC545 70JPS1358). However, the most important role in this area is played by the... 

Several imidazo[2,l-b][l,3]thiazoles based on 2-aminothiazoles were successfully prepared by stirring in methanol at ambient temperature in the presence of HCIO4 as a catalyst [127]. Additionally, it was shown that Groebke reaction involving 2-aminopyrazoles, 2-aminooxazoles, and 3-amino-5-unsubstituted-1,2,4-triazoles also led to the desired products 91-93 (Scheme 40). 

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