Triazoles quaternization

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). 

Thiadiazoles are quaternized to give 3- or mixtures of 2- and 3-alkyl quaternary salts. In 5-amino-1,2,4-thiadiazole, quaternization takes place at the 4-position (90) (64AHC(3il). 1-Substituted 1,2,4-triazoles are quaternized in the 4-position (91), and 4-substituted 1.2,4-triazoles are quaternized in the 1- or the 2-position (92) 64AHC(3)l). 

The latter compound is not the 7-alkyl derivative, and the salt is believed to be 136 by analogy with the quaternization behavior of 1,2,4-triazoles. ... 

The mesomeric effect of the C=S linkage is very pronounced and is responsible for the facile quaternization of heterocyclic N-alkylated thiones (159) this effect is operative even when such a shift does not increase the aromaticity of the ring. Thione derivatives of pyridazine, benzothiazole, quinazoline, 1,3-thiazine, triazole,and isoindole are examples of compounds which readily form quaternary salts. 

Despite the greater acidities of the diazoles and triazoles (pKa = 10-14), fairly vigorous reaction conditions are still required for the alkylation of the unsubstituted systems [26] (Table 5.32) and the effectiveness of the alkylation of pyrazoles and imidazoles is enhanced under solidiliquid conditions [27-30]. Under these conditions, quaternization is avoided if no solvent is added [27],... 

Substituted phenyl azides react with acrolein and morpholine to give A -l,2,3-triazolines (743) (Scheme 149). Hoffmann elimination of A -methylmorpholine from the quaternized intermediates (744) by treatment with Ag20 affords 4-methylene triazoles (745) <86JCR(S)132>. 

Triazoles with alkyl, aryl, or acyl substituents on N(l) or N(4) can be readily quaternized with powerful quaternizing agents such as trialkyloxonium tetrafluoroborates. Quaternization takes place such that maximum separation of the substituents occurs. 

Triazoles (see Section II). 1-Substituted 1,2,3-triazoles (64) readily undergo quaternization at N-3.171,172 Quantitative data are not available, but the fact that methyl fluorosulfonate is required to quaternize isomeric structures 65 suggests that they are much less reactive than 64.173 Since the two isomers show large differences in basicity,174 it seems likely that the large separation in reactivity is not primarily due to... 

The first reported chemical cleavage of 1,2,4-triazoles subjected to the Schotten-Baumann reaction has been refuted. However, 4-benzylaminotriazolyl arenesulfonates are easily cleaved thanks to the loss of aromaticity in the triazolium salt (63JOC543). Another method is quaternization followed by treatment with concentrated alkali [Pg.745]

Triazoles with alkyl, aryl or acyl substituents on N-1 or N-4 can be quaternized. Because of the mesomeric distribution of the positive charge on triazolium compounds, representations such as (63) are convenient but the equivalent formula (64) may be used to denote the site at which quaternization has taken place (the mesomeric nature of (64) must be kept in mind of course). Trialkyloxonium tetrafluoroborates are powerful quaternizing reagents (70JOC2246). 

Quaternization takes place so as to maximize the distance between substituents on annular N. Thus a triazole substituted on N-1 is quaternized on N-4 and vice versa. However, quaternization of triazolinones and triazolinethiones or diquaternization of aromatic triazoles may involve N-1 and N-2. Structural proofs of quaternized compounds are simple in cases such as that of (63) ready removal of the acetyl group from N-1 leaves (65). If then (63) arose from the methylation of (66), the quaternized site is determined unambiguously. 

Quaternization of 4-aminotriazoIes at N-1 (66M141200) or that of 5-amino-l-methyl-1,2,4-triazole at N-4 (63MI4120o) 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)l, 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. 

Quaternization of thiones or thiols proceeds successively through alkylation to methylthio compounds to attack on annular N centres (S9JCS3799. 6ila(641)94, 67JOC224s) to triazolium salts or mesoionic compounds. However, 3,5-bis(methylthio)-l-phenyl-l,2,4-triazole could not be quaternized (54CI(L)1458). 

Quaternization leads to two interesting reactions of C-alkyl-1,2,4-triazoles. The diagnostic value of condensations undergone by a C—Me group situated between two substituted N centres has been mentioned (see Section 4.12.3.2) another example is the determination of the reactive site of (127) that could yield (128) or (129) on tritylation (Scheme 44). Quaternization at the N most distant from the tritylated N-1 or N-2 occurs at N-4 to afford (130) or (131). As the compound obtained does not form a Schiff base, its correct structure is (130) from which (128) is inferred as structure of the trityltriazole (62jcs575). 

Alkyl- and aryl-triazolium compounds are formed mostly by quaternization of preformed triazoles, more rarely by rearrangement of oxadiazoles proceeding through acylamidrazone intermediates. An unusual method (Scheme 136) is the addition of the alkoxydiazenium fluoroborate (312) to the Schiff base (313) to form the triazolium salt (314) through a mechanism that may involve a triazolidine intermediate (315) (69CB3176). 

Hydrazinolysis of (13) produced a 3-(2 -pyrazolin-3 -yl)-[l,2,4]triazole (178) (72JHCU71). The mechanism for this process is given in Scheme 6 which indicates that the addition of hydrazine occurs at the N(5)—C(6) bond of (13) and this is followed by bond cleavage. Hydrazinolysis of (167) resulted in the tricyclic product (179) via an intramolecular cycliz-ation (74MI41501). Ring opening of another quaternized derivative of (13) occurred when... 

In early investigations, when none of the substituents on N could be removed by a selective method, interpretation of the quaternized structure has led to errors. Thus quaternization of 1,3,5-trimethyl-l,2,4-triazole (67 Scheme 22) could afford either or both of... 

Amino-1,2,4-triazoles (50) or their derivatives are usually starting material for the synthesis. They are readily available and already contain the exocyclic N-N bond required for heteroaromatic A-imines. 4-Amino-1,2,4-triazoles can be quaternized by alkyl halides or tosylates at the N-l atom to give the salt 52.79-82 (Scheme 5) The orientation of quatemization is proved by the reactions in Scheme 6 for the example of the quaternary acylamino salts 52. Quaternary salts of the type 52 can also be prepared by reaction of 1,3,4-oxadiazolium salts (51)83 with aryl hydrazines84 and from aryl hydrazine hydrohalides and orthoesters.86 With alkali, the 1-alkyl-s-triazole-4-imines8(7-82 86 can be obtained in the normal manner from these salts (Scheme 5). The free A-imines are all stable except the A-unsubstituted compound itself.87 Recently, other structures were tentatively reported 88 for the deprotonation products of analogous quaternary salts (52) with hydrazine. 

Quaternization of nitrogen atom as a way to activate 1,3-diazole, and 1,3,4-triazole as a diene for the Diels-Alder reaction... 

As we have demonstrated with the example of [4//]-l,2-diazole as a diene for the Diels-Alder addition, there are two critical prerequisites for any five-membered heterocycle to become a diene for the Diels alder reaction the aromaticity of the heterocycle should be diminished as much as possible and the formation of two CC bonds is preferable over formation of a C-heteroatom bond. Because these reactions are LUMO diene controlled, it is helpful if electron-withdrawing substituents are attached to the heterocyclic ring, all of which may be accomplished if the nitrogen in position one of 1,2-diazole and 1,3,4-triazole is quaternized. We expect that these heterocycles should be exceptionally good dienes that promote the formation of the endo cycloadduct due to strong steric repulsion interactions between methyl groups of quaternized heterocycles and the dienophiles. To reinforce the existence of a high localization of the double bonds in... 

When heated with acid (3-),4-(di)substituted 5-amino-l-(l-aroylalkyl)-4/f[l,2,4]triazolium bromides (257) (accessible by quaternization of (3),4-(di)substituted 5-amino[l,2,4]triazoles with... 

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