3-Aminotriazole

Aminotriazole is carboxylated at the 5-position by heating with aqueous sodium bicarbonate in a Kolbe-type reaction (7lJCS(C)l50l). 2-Thiazolinones undergo the Gatter-mann and Reimer-Tiemann reactions at the 4-position, and 3- and 4-pyrazolinone anions on alkylation give 4-alkyl as well as O- and N-alkyl derivatives. 

The 4- and 5-amino-l,2,3-triazoles are diazotizable, e.g. the diazonium salt from 4-aminotriazole-5-carboxamide with potassium iodide gives the 4-iodo derivative, and that from 4-amino-l,5-diphenyltriazole gives 1,5-diphenyltriazole in ethanol (74AHC(16)33). 

A formal ring enlargement of diazirines to five-membered rings is also observed with some hydrazones of ketodiazirines (65CB2509). On attempted preparation of hydrazones (201) from ketodiazirine (200) at 0 C the diazo compounds (202) are plausible intermediates since their transformation to aminotriazoles (203) is known. 

Aminolevulinic acid dehydratase 3-aminotriazole toxicity to, 1, 139 Aminopterin—see Folic acid, 4-amino-Aminopyrine as antipyretic, 1, 172 biological activity, 5, 295 Aminyl, dimethyl-ESR, 7, 19 Amiphenazole... 

Figure 5-18. Rate-equilibrium plot for the isomerization of substituted 5-aminotriazoles at 423 K. ...

An interesting example of how the reaction conditions can influence the structure of the product is shown in Scheme 2-10. Depending on the acidity of the reaction medium and on the reaction time, the diazotization of aminotriazoles (2.18) yields the nitrosoamines (2.19), the chloro compounds (2.20), or the azo coupling products i.e., the triazenes (2.21), as shown by Gehlen and Dost (1963). 

An attempt to prepare triazolotliiadiazepines 31 by reacting bromoalkenecarbonyl substituted thiophenes withiV-aminotriazole thiols failed and triazolo[3,4-h]-l, 3,4-thiadiazines 32 were produced <951JCB939>. 

An example of the aminoacylation of a 5-aminotriazole with a pyrazolide is presented in reference [147] ... 

Imine formation via condensation of aminotriazole 260 with l-methyl-4,5-dioxopyrrolidine-3-carboxylic acid methyl ester 259 leads to formation of the linear tricyclic system 261 under base-mediated conditions (Equation 71) <1997PHA276>. 

In a similar manner, aminotriazole 260 has been condensed with 1 -mcthyM-m ethyl sulfanyl-2,5-dioxo-2,5-dihydro-17/-pyrrole-3-carbonitrile 262 to give rise to analogous product 263 (Equation 72) <1996H(43)1597>. 

Reaction of aminotriazole 260 with the aldehyde 306 under basic conditions led to efficient formation of the central pyrimidine ring of 307 in good yield (Equation 83) <2005HAC200>. 

Chlorocoumarin-3-carbonitrile can undergo reaction with aminothiazoles, aminopyrazoles, and aminotriazoles under basic conditions to give the fused azolopyrimidines 173 (Equation 43) <2002HC0129>. Similar ring systems can also be obtained by the reaction of an aminopyrazole with the bis-chromone 174 (Equation 44) <2003HC0615>. 

The reaction between the aminotriazole 183 and the keto-ester 184 in acetic acid gives the thiopyranotriazolo-pyridine 185 directly (Equation 50) <2002JHC319>. 

Thiadiazinotriazolopyrimidines can be prepared in several ways from the hydrazine-substituted thiadiazino-pyrimidine 186. Reaction with carbon disulfide gives the thione 187 reaction with either anhydrides or orthoformates with sulfuric acid gives the substituted triazoles 188, and reaction with cyanogen iodide gives the aminotriazole 189 (Scheme 47) <2004HC0335>. 

Indicine IV-oxide (169) (Scheme 36) is a clinically important pyrrolizidine alkaloid being used in the treatment of neoplasms. The compound is an attractive drug candidate because it does not have the acute toxicity observed in other pyrrolizidine alkaloids. Indicine IV-oxide apparently demonstrates increased biological activity and toxicity after reduction to the tertiary amine. Duffel and Gillespie (90) demonstrated that horseradish peroxidase catalyzes the reduction of indicine IV-oxide to indicine in an anaerobic reaction requiring a reduced pyridine nucleotide (either NADH or NADPH) and a flavin coenzyme (FMN or FAD). Rat liver microsomes and the 100,000 x g supernatant fraction also catalyze the reduction of the IV-oxide, and cofactor requirements and inhibition characteristics with these enzyme systems are similar to those exhibited by horseradish peroxidase. Sodium azide inhibited the TV-oxide reduction reaction, while aminotriazole did not. With rat liver microsomes, IV-octylamine decreased... 

Cranberry scare (1959, US) Use of aminotriazole, weed killer, thyroid cancer scare... 

No real threat for public health, (a human would have to consume 15,000 pounds of aminotriazole-treated berries every day for a number of years)... 

Treatment of bis(tolylimidoyl) dichloride 358 with 3-aminotriazole (that can exist as two tautomeric structures) affords, after refluxing in THF in the presence of triethylamine, a separable mixture of 5,6-bis-(4-tolylimino)-5//-... 

In the course of the synthetic efforts to isolate 59, a co-crystal containing the starting aminotriazole compound 60 could be obtained depending on the mode of purification (chromatography or crystallization) <2004AXC733>. Crystallographic study of these products showed that the molecules 59 are linked into simple chains, whereas in 60 the components are linked by combination of two-center N-H- N and N-H- O hydrogen bonds. 

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