N-Aminotriazoles

N-Substituted benzotriazole intermediate (77) is an excellant synthon for the synthesis of 2-ethoxy-2-vinylcyclopropanecarboxylate esters (78) [95JOC6], 1-Propargylbenzotriazole was reacted with bromoacetophenone to provide the novel 2-(benzotriazolomethyl)furan (80) in 60% yield [95JOC638]. Annelated N-aminotriazoles, on oxidation, are a good source of cyclic alkynes as illustrated for the reaction of aminotriazolotropone (80) with 4-phenyloxazole to generate the furyl[3,4-cf]tropone (82) from a Diels-Alder intermediate with facile loss of benzonitrile [94TL8421 ]. 

A related approach makes use of an N-aminotriazole such as 5789 or 90) which on oxidation with lead tetraacetate liberates two equivalents of nitrogen along with a hetaryne. An advantage of this method is that a range of temperatures may be used to generate an intermediate. 

Japanese chemists, on oxidation of l-amino-5-phenyl-l,2,3-triazolo[4,5-first example of the ring enlargement on oxidation of N-aminotriazoles. Probably, the reason for this involves the known instability of fivemembered hetarynes, which lower the activation energy for the )V-nitrene rearrangement relative to that for the fragmentation. 

Scheme 17.8 highlights the most recent patented route [via intermediate (1) in the above list] epoxidation of the double bond of 3-(2-chlorophenyl)-2-(4-fluorophenyl)acrylaldehyde is conducted with hydrogen peroxide under basic conditions followed by the reduction of the aldehyde to the corresponding alcohol. The free hydroxyl group is activated by mesylation to the mesyl derivative, which in turn undergoes nucleophilic substitution with symmetrical N-aminotriazole. The attacking nitrogens are the ones free from the N-amino functionality. The N-aminotriazolium obtained is then reduced with sodium nitrite under acidic conditions to afford epoxiconazole. 

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. 

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. 

Bis acylhydrazones or bis aroylhydrazones of a-diketones also give derivatives of 1-aminotriazoles on mild oxidation (Scheme 21).i n The product was originally assigned a dihydrotetrazine structure, and other possibilities were considered,but Curtin and Alexandrou proposed the isoimide structure (8) which was, for the product obtained from biacetyl bis(benzoylhydrazone), confirmed by X-ray crystallography. The mechanism given in Scheme 21 has been put forward for its formation ... 

Figure 1 HOMO-LOMO Interaction between diphenylnitrilimine and l-(N-phenylacylidene)aminotriazole.

Mass spectral studies can distinguish between the N(4) and NH2 substitution of 3-aminotriazole in compounds (17) and (18) <88JHC565>. In (17) the base peak is at m/e 220, whereas this fragment is very small in (18), the base peak being at m/e 84. 

Triazole melts at 120-121 °C and boils at 260 °C. It has a density of 1.132 and a specific conductivity of about 10 0 cm , of the same order as imidazole. Triazole dissolves readily in water and ethanol but is only slightly soluble in ether. Substitution on N(l) usually lowers the melting point this effect is usually much smaller for substitution at N(4), although 4-aminotriazole has a melting point of 84-86°C. 3-Aminotriazole has a melting point of 159°C and the 3-thiol derivative of 221-... 

Aminotriazole (38) can be alkylated at N(4) with benzyl or acyl bromides in moderate to good yield to give the corresponding bromides (39) <898269,90S707>. These salts can be converted into the corresponding 5-triazolinethiones (40) and into 5-triazolinones (42) via (41) (Scheme 6). 

Aminotriazole (27) reacts with halomethyltrimethylsilanes (43) to give a mixture of the N(l) (44) and C(3) alkylated (45) derivatives, the former predominating (Equation (15)) <90ZC285>. 

Aminotriazole carboxylic AcidsyC,H4N4Oj, mw 128.09, N 43.74%. The following isomers and some derivatives are described in the literature ... 

Addnl Refs on Aminotriazoles and Their Derivatives a)J.Reilly P.J.Drumm.JCS 1926,1729—37[Prepn and props of aminopropyi -1,2,4-triazoles and their salts and derivs. One of the derivs described in this paper is expl. See also diazo-5-isopropyl-asym(l,2,4)-triazole, under D s] b)O.Dimroth W. Michaelis,Ann 459,39-46(1927) CA 22,423 (1928) (Discussion on intramolecular rearrangement of 5-anunc-1,2,3-trlazole derivative RaHN-C-NR -N R HN.C-NRl-N... 

Hydrolysis of the N-alkyl derivatives of l,2,3-triazolo[4,5-d]pyrimidines 47-51 to give N-alkyl-4-aminotriazole derivatives 52-56, respectively, took place with dilute acid or base at room temperature [57JOC707 65JOC2488 69JCS(C)2379 74JCS(P1)2030 77JCS(P1)1819] (Scheme 10). 

Similarly, 1,3 -dipolar cycloadditions of benzenesulfonyl azides to N,N- diethylaminoprop-1-yne led to 1,2,3-triazoles (72a) and a-diazoamidines (72b). With the aid of IR and H NMR data these were shown to exist in a tautomeric equilibrium (70JOC3444). With IR and H NMR data a 5-aminotriazole-diazoamidine equilibrium (73a) s (73b) was established (70TL2823, 72CB2963, 72CB2975). However, 4-amino-l,2,3-triazole (74a) proved to be stable and no ring-chain tautomerism could be identified (73TL1137). 

Methylation of 3-amino-l,2,4-triazoIe does not afford the methylamino derivative but all the three annular JV-methyl derivatives are obtained in ratios that depend on the basicity of the reaction mixture (73bsfis49). Similar results have been obtained in the case of ribosylation and other instances (siHC(37)i p. iso). Alkylation of aminotriazoles on N-4 is rare. 

Activated aromatic halides and 2- or 4-pyridyl halides can be used for the N-arylation of 1,2,4-triazoles, best achieved by the Ullmann technique (70JCS(C)8s). Preference for annular arylation on N-1 rather than N-4 is observed but arylations of 3-aminotriazoles with picryl chloride are anomalous the parent triazole itself is substituted on N-1 but in... 

The formation of dihydro or tetrahydrotetrazine intermediates in Pellizzari type reactions carried out at high temperatures has long been suspected. The conversion of diphenyl-tetrazine (275) into 3,5-diphenyltriazole (276) by reduction (62LA(654)146) occurs in two stages (Scheme 121). Formation of the aminotriazole (277) may be interpreted as an intramolecular leacylation of the amidrazone analogue derived from (275) followed by reductive cleavage of N(4)—NH2. The conversion of (275) into (276) with ethanolic alkali also is consistent with the known lability of N(4)—NH2. 

Nucleophilic additions to the acetylenic bond in various short-life cyclic acetylenes including optically active derivatives have been extensively studied . The formation of 1,2-di-bromocycloheptcne was also observed in the bromine oxidation of the aminotriazole derivative 21 n = 7). ... 

Quaternization of 4-aminotriazoles at N-1 (66M141200) or that of 5-amino-l-methyI-l,2,4-triazole at N-4 (63MI41200) follows the rule predicting attack on N-centres at maximum separation. Much the same applies to the quaternization of azo dyes derived from triazole <81HC(37)1, p.609> except that 1,4- and 2,4-patterns of substitution are equivalent under this rule even the 1,2-isomer may be formed. 

The acetates of acetamidine and benzamidine were condensed with 4-aminotriazole-S-carboxamide (73a) and its 7- and 8-methyl derivatives to give 2-metoyl- and 2-phenyl-8-azapurin-6-ones, respectively, in 80-90% yield, after refluxing for 4 - 8 h in butanol, hexanol, or octanol (toe choice of solvent determined toe optimal yield in each case). The reaction with tri-chlOFoacetamidine terminated at, e.g., (a-amino-i ) )9-trichloroethyliden-amino) 1,2,3-triazole (84) (from 73a). These intermediates were cyclized to 2-trichlorometoyl-8-azapurin-6-ones, in excellent yields, by stirring with 0.5 N potassium hydroxide (24°C, 5 h). This reaction gave only poor yields with 73b,c. 

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