Triazoles methylation

In the early development of n-triazole chemistry a number of reactions leading to the 4,5-dicarboxylic acids and their derivatives were discovered and should be explored further. Fries oxidized benzotriazoles (Eqs. 46,47) and prepared a broad range of acid derivatives. Some especially promising compounds in this series have been prepared from what was then called a hydrazoic acid polymer (4.3-1) by reaction with nitrous acid (Eqs. 48,49). Although the yields were not reported, the chemistry is intriguing. The oxidation of a 1,2,3-triazole methyl group and conversion to acid... 

The 3-amino group brings a second nucleophilic center in these structures thus 2-imino-3-amino-4-methyl-4-thia201ine (409) reacts with methyl diloroformate to give the bicyclic compound (410) (Scheme 234). Other thiazolo-s-triazoles of the [3.2-l>] type have been obtained by... 

C2N3 N N N — — l,3-Dimethyl-4-(l,2,3-triazolyl) sulfide 3-methyl-2-phenyl-l,2,3-triazol-l-ine-4-thione... 

For the NH azoles (Table 3), the two tautomeric forms are usually rapidly equilibrating on the NMR timescale (except for triazole in HMPT). The iV-methyl azoles (Table 4) are fixed chemical shifts are shifted downfield by adjacent nitrogen atoms, but more by a pyridine-like nitrogen than by a pyrrole-like iV-methyl group. 

Ring substituents can have a considerable effect on the acidity of the system. In the 1,2,4-triazole series a 3-amino group decreases the acidity to 11.1, a 3-methyl group to 10.7, whereas a 3-phenyl group Increases the acidity to 9.6, and 3,5-dlchloro substitution to 5.2 (71PMH(3)1). 

Despite the weak basicity of isoxazoles, complexes of the parent methyl and phenyl derivatives with numerous metal ions such as copper, zinc, cobalt, etc. have been described (79AHC(25) 147). Many transition metal cations form complexes with Imidazoles the coordination number is four to six (70AHC(12)103). The chemistry of pyrazole complexes has been especially well studied and coordination compounds are known with thlazoles and 1,2,4-triazoles. Tetrazole anions also form good ligands for heavy metals (77AHC(21)323). 

For both azole and benzazole rings the introduction of further heteroatoms into the ring affects the ease of quaternization. In series with the same number and orientation of heteroatoms, rate constants increase in the order X = 0requires stronger reagents and conditions methyl fluorosulfonate is sometimes used (78AHC(22)71). The 1-or 2-substituted 1,2,3-triazoles are difficult to alkylate, but methyl fluorosulfonate succeeds (7IACS2087). 

N-Unsubstituted 1,2,3-triazoles are methylated mainly in the 1-position with methyl iodide and silver or thallium salts, but mainly in the 2-position by diazomethane. There is also some steric control. For example, 4-phenyl-l,2,3-triazole with dimethyl sulfate gives the 2-methyl-4-phenyl (38%) and l-methyl-4-phenyl isomers (62%), but none of the more hindered 1-methyl-5-phenyltriazole (74AHC(16)33). JV-Unsubstituted 1,2,4-triazoles are generally alkylated at N-1. 

Halogeno-l-methyl-l,2,3-triazoles undergo substitution reactions with amines, but the 4-halogeno analogs do not. 5-Chloro-l,4-diphenyl-l,2,3-triazole with sodium cyanide in DMSO gives the cyano derivative (63JCS2032). 1-Substituted 3-chloro- and 5-chloro-l,2,4-triazoles both react with amines. 

Phenylisoxazolin-5-one condensed with anthranal to give a tricyclic isoxazolylquinoline (Scheme 72) <78CZ264). 3-Methyl-4-phenylazoisoxazoline-5-thione reacted with ethyl chloroacetate for form an intermediate isoxazolethiol, which on heating generated a 1,2,3-triazole (Scheme 73). 

The 1-azirines obtained from the vapor phase pyrolysis of 4,5-disubstituted 1-phthalimido-1,2,3-triazoles (157) have been found to undergo further thermal reactions (71CC1S18). Those azirines which contain a methyl group in the 2-position of the ring are cleaved to nitriles and phthalimidocarbenes, whereas those azirines which possess a phenyl substituent in the 2-position rearrange to indoles. 

Triazole, rrans-5-bromo-4,5-dihydro-4-methyl-l-(4-nitrophenyl)-... 

Triazole, rrans-4-methyl-1 -<4-nitrophenyl)-5-propyloxy-4,5-dihydro-... 

Triazole-4-carboxylic acid, 5-methyl-1-phenyl-UV, 5, 685 (68JCS(C)1329, 58G977)... 

Thieno[3,4-d][ 1,2,3]triazole, tetramethyl-synthesis, 6, 1015 Thieno[3,4-c][ 1,2,3]triazoles synthesis, 6, 1042 Thieno[3,4-d][ 1,2,3]triazoles reactions, 6, 1036 synthesis, 6, 1044 Thienyl radicals generation, 4, 832 Thiepane, 2-acetoxy-synthesis, 7, 574 Thiepane, 2-chloro-nucleophilic substitution, 7, 573 synthesis, 7, 574 Thiepane, 2-methyl-synthesis, 7, 573 Thiepane, 2-phenyl-synthesis, 7, 573 Thiepane, 3,3,6,6-tetramethyl-cycloaddition reactions, 7, 574 Thiepanes, 7, 547-592 applications, 7, 591... 

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