1,3,4-Triazoles addition reactions

The addition of phthalimidylnitrene (374) to simple alkynes affords 1-azirines in yields of 1-15% (Scheme 10). In this reaction, which is of no real preparative value, the symmetrical 2-azirines (375) were suggested as the most plausible intermediates and unequivocal proof of the existence of such species was demonstrated from a series of 1,2,3-triazole pyrolysis reactions <71CC1518). Extrusion of nitrogen from the regioisomeric 4,5-disubstituted 1,2,3-triazoles (376) during flash vacuum pyrolysis furnished identical product mixtures which included both regioisomeric 1-azirines (377). 

Since both oxepin and its valence isomer benzene oxide contain a x-tb-diene structure they are prone to Diels-Alder addition reactions. The dienophiles 4-phenyl- and 4-methyl-4//-l,2,4-triazole-3,5-dione react with substituted oxepins at room temperature to give the 1 1 adducts 7 formed by addition to the diene structure of the respective benzene oxide.149 190,222... 

The other major approach to triazolo[4,3-a]pyridines is from pyridines or from 2-halogenopyridines, with the addition of a three-atom fragment to form the triazole ring. Reaction between pyridine or 4-methylpyridine and... 

The addition reactions of aryl azides onto enamines bearing a carbonyl, sulfonyl, or nitro group in the 0 position with respect to the nitrogen atom have been investigated by Italian authors.240-241 The expected triazoline derivatives could not be isolated but were immediately converted into the corresponding 1,2,3-triazoles (49) and secondary amines. The reaction of p-nitrophenyl azide with l-benzoyl-2-morpholino-l-propene (48) is given as a typical example. 

Cyclization of 3-Amino-1,2,4-triazoles by Reaction with Alkylidene- or Arylidenemalononitrile. [3 + 3] Cycloaddition of 3-amino-l,2,4-triazole (65) onto 4-methoxybenzylidenemalononitrile produced only the 7-amino-6-cyano-5-(4-methoxyphenyl)-l,2,4-triazolo[4,3-a]pyrimidine (66) [88IJC(B) 478)]. The alternative addition that may afford the 5-amino-6-cyano-7-(4-methoxyphenyl)-l,2,4-triazolo[4,3-a]pyrimidine (110) did not take place. Utilization of ethoxymethylene malononitrile in place of arylidenemalononitrile in this reaction gave 66 (R = H) in addition to 7-amino-6-cyano-l,2,4-triazolo[l,5-a]pyrimidine 67 (R = H) (70JPR254) (Scheme 46). 

Azide addition to an active methylene compound in the presence of a base involves a triazoline intermediate that aromatizes to a triazole the reaction is a well-established route to 1//-triazoles6-8 bearing a 5-amino or hydroxy substituent and an aryl or carbonyl-containing function in the 4-position. The proposed triazoline intermediates have been detected in the reaction of azides with aliphatic ketones (see Scheme 64, Section Il,A,3,f). 

This reaction sequence is representative for the synthesis of 1,2,4-diazaphospholes, which are the phosphorus analogues of the 1,2,4-triazoles. The reaction behaviour resembles that of pyrazoles with an additional reaction centre provided by the P=C double bond. 

Deactivation against electrophilic attack accounts for the difficulty or failure of nitration, sulfonation and iV-oxidation of 1,2,4-triazoles proper. However, triazolate anions react readily with electrophilic reagents alkylation and acylation have received much attention but halogenation and addition reactions less. Systematic study of the formation and reactions of salts and metallic complexes is of recent origin. 

Alkenyl- and alkynyl-triazoles have received little attention. By analogy with the behaviour of other azoles they are expected to polymerize but to be less reactive in addition reactions than alkenes or alkynes. Although the most promising polymers derived from triazoles are obtained by different methods (see Section 4.12.5.2.3), some information is available on potentially polymerizable vinyltriazole (63MI4120i). The styryltriazole (134) could be oxidized to 3-methyl-l-phenyl-l,2,4-triazole, i.e. without affecting either the triazole or iV-phenyl ring, but hydroxylation of the alkene chain failed (s4JCS4256). 

Treatment of (22) with hot aqueous sodium hydroxide gave 3-(2-aminophenyI)-1,2,4-triazole (208). Evidence that this latter reaction involved an initial attack of hydroxide ion at the 5-position arose from the isolation of 3-(2-benzamidophenyl)-l,2,4-triazole (209) upon the action of hot base on 5-phenyI-[l,2,4]triazoIo[4,3-c]quinazoline (210). Apparently, under these rearrangement conditions, hydrolysis of the intermediate amide, for example (209), is faster than ring closure to the [1,5-c] isomer. Similar ring opening reactions were observed with the [1,5-c] series, a system which also underwent typical alkenic addition reactions at the C(5)—N(6) double bond (70JOC3448). 

The H-1 atom of 4,5-dibromo-l,2,3-triazole (147) (67G109) is very acidic and forms instantly the triazolide salt (148) when treated with dimethylamine (67G109). The salt is stable even when heated to 260 °C for 140 hours and reacts smoothly in a conjugate addition reaction to give (149) (54JA4933). Methylation of (148) gives both the 1-methyl-IH and 2-methyl-2H derivatives (150) and (151) (70JHC961). 

Alkynes undergo 1,3-dipolar addition reactions with organic azides to form triazolesCommonly, hydrazoic acid additions to alkynes also give triazoles and this aspect of their chemistry has been... 

This addition reaction has been used for the preparation of a large number of substituted triazoles, using various ty pes of azides and acetylenes including cycloalkynes . 

Anodic oxidation of benzylidenephenylhydrazine gives diarylnitrileimine, which may react with suitable dienophiles in a 1,3-dipolar addition reaction. Pyridine [130], some alkenes, and iV-heterocycles [131] may act as dienophiles with formation of substituted 1,2,4-triazoles (XL) or pyrazolines ... 

Several addition reactions of unsaturated phosphonic and phosphinic esters have been reported during the course of the year. Dithiophosphoric acids add to 2-alkoxy-vinylphosphine esters in the expected manner, and in the addition of phenyl azide to vinylphosphonates, the initial triazole (95) may be thermolysed to a C-phosphory-lated aziridine, but in the presence of triethylamine the final products are 2-anilino-vinylphosphonates. ... 

The converse addition of a phosphorus-containing dipolar reactant to a dipolarophile which lacks phosphorus is exemplified by the addition reactions of diethyl (1-azidoalkyl)-phosphonates (503) to acetylenic compounds to give the 1,2,3-triazoles 504 [X = H, Me, Ph, COPh, or COOMe Y = COOMe, COOEt, P(0)(OEt)2, or P(0)PhJ related reactions have also been carried out with the ester 503 (R = NHR ) The (l-diazoalk-2-enyl)phosphonates 505 readily cyclize to 506 and the diazoamide 507 (Z = NH2) also behaves analogously to give 508 , but may (for Z = OMe or OEt) react in an intermolec-ular fashion. ... 

S.2.2.4. Triazoles from Azides. Cycloadditions of this type constitute a valuable synthetic route to the triazole ring system. This is shown in Scheme 5.30. This combination dates back to the early work of Huis-gen, but in more recent times it was discovered to be subject to catalysis by Cu(I) compounds. The reactions are fast under mild conditions, have high regiospecificity, and occur in a variety of solvents including water. In addition, reaction products are easily isolated. Reactions with these characteristics have become known as comprising click chemistry this term was coined by K. B. Sharpless. The first and most commonly used reaction referred to by this name is indeed the azide-alkyne cycloaddition, and new interest has developed in triazole hemistry since the discoveiy of the copper catalysis. In addition to its use in organic... 

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