1.2.4- Triazole weak base

The 1,2,3-triazole 1-oxides 326 are usually stable, crystalline, semipo-lar, and colorless compounds. The lower 2-alkyl-substituted 1,2,3-triazole 1-oxides tend to be slightly hygroscopic. They act as very weak bases, protonation requiring acids like triflic acid and O-alkylation requiring tri-methyloxonium salts. No pKa values have been reported. 

The 3-alkyl- or aryl-substituted 1,2,3-triazole 1-oxides 448 are usually stable, crystalline, polar, and somewhat hygroscopic compounds. 3-Sub-stituted 1,2,3-triazole 1-oxides 448 are weak bases being subject to protonation at the negatively charged oxygen atom. 3-Hydroxy-l,2,3-triazole 1-oxide 456 (R=OH) acts both as a base and as an acid. No pKa values for 3-substituted 1,2,3-triazole 1-oxide have been reported. 

Base catalyzed Hofmann elimination carried out on the quaternary ammonium salts (61) gives (62). Good nucleophiles, but relatively weak bases, add at room temperature to the activated double bond of (62), affording (rans-4,5-dihydro-l,2,3-triazoles (63) (80JHC267). 

A modern example of an agent used against human fungal infections is Pfizer s fluconazole, which actually contains two triazoles. The first is added as the anion to an a-chloroketone and the second is added to an epoxide made with sulfur ylid chemistry (you will meet this in Chapter 46). Note that weak bases were used to catalyse both of these reactions. Triazole is acidic enough for even... 

Protection of carboxylic acids. The 2-(2-pyridyl)ethyl group is useful for protection of amino acids. The esters are obtained by reaction with 1 and DCC/1-hydroxybenzo-triazole. The group provides higher solubility in protic solvents, and is stable to both acids and bases. It is removed by treatment with methyl iodide and a weak base. 

Examples adduced in Scheme 87 indicate the caution required when a nitrilimine intermediate favours the formation of a heterocycle other than triazole. The bromo derivative (179) of the semicarbazone (180) is formally analogous to (172) the nitrilimine (181) is formed even in the presence of such weak bases as sodium acetate or water and undergoes ring closure to the 1,3,4-oxadiazole (182), In anhydrous acetic acid the triazolinone (183 R = H) is formed (72JCS(P1)1918) a similar reaction occurs on treating the iV-methyl homologue of (180) with bromine in acetic acid to obtain (183 R = Me). 

Triazoles are weak bases. 1,2,3-Triazole, with Ka = 1.17, is less basic than pyrazole. 

Benzotriazole is an extremely weak base, but with a = 8.2, it is a stronger NH-acid than indazole, benzimidazole or 1,2,3-triazole. The fused benzene ring imparts additional stabilization to the conjugate base ... 

Triazole is a weak base, = 2.19. Protonation occurs at N-atom 4. 1,2,4-Triazoles unsubstituted on nitrogen are NH-acidic and their copper and silver salts are sparingly soluble. The parent compound has a i Ka of 10.26. Hence 1,2,4- and 1,2,3-triazole differ very little in basicity and acidity. 

Basic Compounds. Pesticides such as the 5-triazines and triazoles behave as weak bases in aqueous solutions (72, 73). They readily associate with hydrogen to form protonated species as shown in Equation 2, and the amount of each species in solution is governed by the equilibrium expression in Equation 3 ... 

Benzotriazole is a very weak base, but (with pK = 8.2) is an N-H-acid stronger than 1,2,3-triazole (pKa = 9.3), benzimidazole (pKa = 12.75) and indazole (pKa = 13.86). In its conjugate base, the benzimidazolyl anion (1), the fused benzene ring apparently participates in the delocalization of the negative charge and thus effects additional... 

Contributions in this section are important because they provide structural information (geometries, dipole moments, and rotational constants) of individual tautomers in the gas phase. The molecular structure and tautomer equilibrium of 1,2,3-triazole (20) has been determined by MW spectroscopy [88ACSA(A)500].This case is paradigmatic since it illustrates one of the limitations of this technique the sensitivity depends on the dipole moment and compounds without a permanent dipole are invisible for MW. In the case of 1,2,3-triazole, the dipole moments are 4.38 and 0.218 D for 20b and 20a, respectively. Hence the signals for 20a are very weak. Nevertheless, the relative abundance of the tautomers, estimated from intensity measurements, is 20b/20a 1 1000 at room temperature. The structural refinement of 20a was carried out based upon the electron diffraction data (Section V,D,4). 

Lithium Salts Based on Heterocyclic Anions. Lithium salts based on organic anions where the formal charge is delocalized throughout substituted heterocyclic moieties were also reported sporadically, which included, for example, lithium 4,5-dicyano-l,2,3-triazolate ° and lithium bis(trifluoro-borane)imidazolide (Lild). ° The former was developed as a salt to be used for polymer electrolytes such as PEO, and no detailed data with respect to electrochemistry were provided, while the latter, which could be viewed as a Lewis acid—base adduct between LiBp4 and a weak organic base, was intended for lithium ion applications (Table 13). 

Both ring positions and lateral positions - both at C4 and C5 - are activated by the O-silylation. Substituents can be introduced at the lateral 5-position by O-silylation followed by abstraction of the activated lateral proton with a weak non-nucleophilic base. The neutral species 428 formed is subject to nucleophilic allylic displacement of the silyloxy anion rendering laterally substituted triazole 429 in one pot (Scheme 121). 

The importance of the stereochemical, intermolecular, and polymorphic analysis of the various heterocyclic drugs were studied. The stereochemical analysis were carried out for piperidine and azepine derivatives, weak TT-interaction studies were pursued for isoxazole, imidazole, indole, quino-Une, and triazole and the polymorphic analyses were done for two commercially available drugs, valdecoxib and sildenafil citrate. These analyses were correlated with the crystal structures of their respective drugs that were foimd in complex with the receptor. The influence of these parameters over the drug s activity were explained. Even though these analyses were based on solid-state conformations, it can provide a wealth of information for the drug design community. 

A ratiometric sensor 4 for Cd " and Zn " based on calix[4]arene bearing 1,2,3-triazole-linked pyrene units has been reported (Fig. 28.2) [30]. Probe 4 showed strong excimer and weak monomer emissions, due to face-to-face jt-interactions. Addition of Cd " or Zn produced a ratiometric fluorescence change, with a decrease in excimer emission and an increase in monomer enussion. This ratiometric behavior is due to the complexation of Cd " and Zn " by the triazole nitrogen atoms, which causes a change in the conformation of the pyrene arms. No other metal ions produced such ratiometric response, confirming the high selectivity of probe 4. 

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