Benzotriazoles tautomerism

Annular tautomerism (e.g. 133 134) involves the movement of a proton between two annular nitrogen atoms. For unsubstituted imidazole (133 R = H) and pyrazole (135 R = H) the two tautomers are identical, but this does not apply to substituted derivatives. For triazoles and tetrazoles, even the unsubstituted parent compounds show two distinct tautomers. Flowever, interconversion occurs readily and such tautomers cannot be separated. Sometimes one tautomeric form predominates. Thus the mesomerism of the benzene ring is greater in (136) than in (137), and UV spectral comparisons show that benzotriazole exists predominantly as (136). 

To illustrate the results summarized in Table IX, some examples are discussed in detail. The large number of papers discussing the annular tautomerism of azoles (first column) is exemplified by the studies concerning benzotriazole (57). Wofford, Forkey, and Russell, using pyrazoles and imi-... 

New IR techniques introduced for the study of prototropic tautomerism include IR dicroism for the photoinduced double proton transfer in por-phine 71 (Scheme 24) [89CPH(136)165], and IR spectroscopy in a supersonic jet (less than 50 K) for demonstrating the presence, in these conditions, of 2//-benzotriazole (57b) [96CPL(262)689]. 

Fyrazoles and indazoles, imidazoles and benzimidazoles/ and benzotriazoles which possess a free NH group are associated and have been considered to exhibit mesohydric tautomerism see discussion in Volume 1, article I, Section I,C. 

Benzotriazole can exist in two tautomeric forms, l-//-benzotriazole (6.46, R = H) and 2-/f-benzotriazole. If the aromatic ring contains a substituent, the 1- and 3-nitrogen atoms of the triazole are not equivalent, and therefore a 3-//-benzotri-azole derivative can also exist. The equilibrium between the 1 -H and 2-H tautomers of benzotriazoles is strongly on the side of the 1 -H tautomer, in contrast to triazole where the 2-H tautomer is dominant. Tomas et al. (1989) compared experimental data (enthalpies of solution, vaporization, sublimation, and solvation in water, methanol, and dimethylsulfoxide) with the results of ab initio theoretical calculations at the 6-31G level. 

Tomas et al. [281] have calculated the tautomeric equilibrium of 1,2,3-benzotriazole in the gas phase and compared their results to experimental data [282] derived from ultraviolet spectroscopy. Experiment suggests that 35 is about 4 kcal/mol more stable than 34 this result is consistent with calculations [281] at the MP2/6-31G level, which predict 35 to be 2.5 kcal/mol more stable than 34. The same level of theory predicts 33 to be 5.0 kcal/mol more stable than 32 in the parent triazole system. Although experimental data are available indicating 35 to be the dominant tautomer in CDCf and d6-dimethyl sulfoxide solutions [279, 283], this equilibrium does not appear to have been the subject of any modeling, continuum or otherwise. It may prove to be somewhat challenging, however. Tomas et al. point out that correlation effects favor 35 by about 5 kcal/mol at the MP2 level AMI, PM3, and HF calculations with moderate basis sets all predict... 

The C chemical shifts of benzotriazole in the solid state are obtained using the CP-MAS technique. The chemical shifts are slightly different from those observed in DMSO-dg or CDCI3 <83H(20)1713>. CP-MAS C NMR spectroscopy is a powerful tool which enables determination of the tautomeric structure of benzotriazole in the solid state. Thus, the solid-state C NMR spectra of some A-(dialkylaminomethyl)benzotriazoles support the existence of only the N(l) isomer <87JCS(P1)2673>. 

Tautomerism was only treated briefly in CHEC-I <84CHEC-i(5)67l> under the section of thermal and photochemical reactions. Tremendous effort has been devoted to the study of the tautomerism, both prototropic and ring chain, of 1,2,3-triazoles and benzotriazoles. Therefore, tautomerism is described is considerably more detail in CHEC-II. For tautomerism of 1,2,3-triazolines, see Section 4.01.5. 

The annular prototropic tautomerism of the parent 1,2,3-triazole and benzotriazole are described in CHEC-I <84CHEC-I(5)691> and was reviewed earlier <76AHCS295>. 

The understanding and discussion of pK (AG°) values needs knowledge of the structure of the species involved in the equilibrium. The problem of the tautomerism of neutral species is well known [Section IV,G and reference (76MI3)]. However, it is often not recognized that a similar problem arises with charged species, e.g., in cations formed on protonation of neutral molecules having two or more basic sites. This tautomerism can be classified as annular, as in benzotriazole (10) protonated forms, or as functional, as in 1-methyl-4-aminopyrazole (529) cations. 

It must be stressed that a statement that benzotriazole protonates on N(3) or that l-methyl-4-aminopyrazole does on the amino group, means only that this is the dominant species in an equilibrium. Experimentally, the tautomeric equilibrium constant between cations can be determined by the general methods used to study tautomerism. Even pK s can be used, if the second protonation of quaternary salts as fixed derivatives are measured. 

To suppress enamine-derived side products, we explored addition of benzotriazole (BtH) to the reaction mixture. The premise behind these experiments was the ability of BtH to form stable adducts with imines,23,24 thereby blocking tautomerization of 19 to 20 through in situ formation of the benzotriazolyl derivative 21. It was hoped that subsequent hydride displacement of the Bt moiety would afford the desired mono alkylated products 23. Indeed, analytical high-performance liquid chromatography (HPLC) revealed a remarkable improvement in terms of product purity, especially for reactions carried out at room temperature, with the desired secondary anilines 23 being essentially the only products detected. In... 

The reliability of semi-empirical methods (AMI, PM3, and MNDO) for the treatment of tautomeric equilibria has been tested for a series of five-membered nitrogen heterocycles, including 1,2,3-triazole and benzotriazole. The known tendency of MNDO to overestimate the stability of heterocycles with two or more adjacent pyridine-like lone pairs is also present in AMI and to a somewhat lesser extent in PM3. Tautomers with a different number of adjacent pyridine-like nitrogens cannot be adequately treated by these semi-empirical methods. Both AMI and PM3 represent major improvements over MNDO in the case of lactam-lactim tautomerism. The stability of N-oxides as compared to N-hydroxy tautomers is overestimated by PM3 method. All three methods give reliable ionization potentials and dipole moments (90ZN(A)1328). 

There is a growing interest in the use of 15N NMR spectroscopy for elucidation of various structural problems of azole chemistry, especially tautomerism. For example, the mole fractions of the prototropic tautomers were obtained from the 15N chemical shifts of the NH tautomers and the corresponding N-methyl derivatives. By this method, the average mole fraction for the 2-NH tautomer of benzotriazole is 0.02 in both CDC13 and DMSO, and that of 1,2,3-triazole is 0.34 in CDC13 and 0.55 in DMSO (82JOC5132). 

The tautomeric equilibrium of unsubstituted benzotriazole has been studied extensively as summarized in reviews (63AHC(2)27, 76AHCS295). In the crystalline state the sole existence of 1H-benzotriazole is demonstrated by X-ray (74AX(B)1490), by 13C NMR (83H(20)1713), and by microwave spectra (93JSP)161)136). The 1 //-form also predominates strongly under most other conditions. 

This section covers ligands containing the 1,2,3-triazole ring system. These include, in addition to the parent triazole, various N- and/or C-substituted triazoles, benzotri azole, and a number of 8-azapurines. The coordination chemistry of 5-thio-l,2,3,4-thiatriazole is selectively reviewed. All of these molecules, with the exception of the N-substituted triazoles, are capable of coordinating in anionic as well as neutral form. 1,2,3-Triazole, first prepared by von Pechmann in 1888 (215), is a weak acid (p/ a = 9.26) (88) and exists as a mixture of the tautomeric forms (structures la and lb). Benzotriazole (2), first correctly formulated... 

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