Nitro tautomer

Fig. 2. The proton magnetic resonance spectrum of 5-nitrobenzofuroxan, in acetone at — Sl C. The bands marked by arrows arise from the 5-nitro tautomer.

This is an acid-catalyzed SN2 displacement from the protonated ad-nitro tautomer. The substrate is not protonated in even the strongest acids used the protonation site shown in Scheme 2 is not the most basic, but the only one that results in decomposition. Bisulfate is a poorer nucleophile than water by a factor of about 1000,119 but above 80 wt% in acidity its concentration is at least 1000 times that of water.150 Twelve compounds were studied the intercept... 

While dealing with imidazoles, an important characteristic is their annular tautomerism. A tautomeric equilibrium for many imidazoles is rapidly achieved at room temperature. In some tautomeric pairs, though, one tautomer often predominates over the other. For instance, 4(5)-bromoimidazole favors the 4-bromo-tautomer in a 30 1 ratio, whereas 4(5)-nitroimidazole exists predominantly as the 4-nitro tautomer (700 1) [11]. 4(5)-Methoxyimidazole has a ratio of 2.5 1 for the 4- and 5-methoxy tautomers. 

A second and related consequence in aliphatic nitro compounds is the acidification of the directly bonded CH unit through the attendant stabilization of the derived conjugate bases (5,6). As with all delocalized anions, reprotonation gives rise to tautomers, the original C-nitro compound (I) and the oci-nitro or isonitro form (II), Eq. 2.1. The aci-nitro tautomers are typically present in very minor concentrations, with equilibrium constants (A eq) between 10 and 10 (7). Alkylation of the delocalized anion leads to both a-substituted nitro compounds and the regioisomeric nitronic esters (nitronates). Nitronates were described as early as 1894 (8), however, the first isolated nitronic ester was obtained several years later upon the addition of diazomethane to phenylazonitromethane (1), Eq. 2.2 (9). 

At high buffer concentrations, positive curvature may be observed in buffer dilution plots, indicating that the general acid and base are simultaneously participating in the rate-determining step.27 In such a case, the rate law must be expanded by third-order terms. Furthermore, plots of buffer slopes versus xHb may be nonlinear, when the unstable tautomer is a diprotic acid as, for example, the aci-nitro tautomer of nitrobenzene.28... 

Yim and Liu [145] used a combined ab initio molecular dynamics (MD) study to reveal several new mechanistic paths that are energetically favored over dissociation of the C-N02 bond. Their study indicated dissociation of NTO via an aci-nitro tautomer followed by ring scission to a ketinimine intermediate as the most favorable pathway (Scheme IX), requiring only 38 kcal/mol as compared to the 62.5 kcal/mol needed for cleaving the C-N02 bond. Kohno et al. [151] conducted a theoretical study on the decomposition of the NTO dimer. They reported that HONO elimination is the last step of a cascade of reactions with a total barrier of 88 kcal/mol. 

As with pyrazoles, the introduction of the nitro group into the imidazole ring position 4(5) leads to an approximately 30 ppm lowfield shift of the tpxo-carbon signal resonance (Tables 3.6 and 3.10) [24, 321-329], Thus, the chemical shift of the carbon atom bonded to the N02 group (C-ipso) is 149.2 ppm, whereas that of neighboring carbon (C-5) is 119.8 ppm. In 1-substituted 4-nitroimidazoles (Table 3.11) the shifts of the same carbons are 146 1 and 122 2 ppm, while in 1-substituted 5-nitroimida-zoles they are 138 1 and 132 1 ppm, respectively (Table 3.12). All this may be indicative of the possible existence of 4(5)-nitroimidazole as a 4-nitro tautomer. Moreover, another support for the structure may be provided by comparison of the proton spin-spin coupling constants - J, 2J and 1/ Cl I-111) [321, 322, 330],... 

As seen from Table 3.41, the half-wave potentials of 3(5)-nitropyrazole and l-methyl-3-nitropyrazole are practically identical at all pH values. In the authors opinion, this may be due to the fact that 3(5)-nitropyrazole contains, mainly, 3-nitro tautomer [904], A similar regularity is observed for 4(5)-nitroimidazole and 1-methyl-4-nitroimidazole [903], The E1/2 values of l-methyl-3-nitropyrazole lie in more a negative region than those of l-methyl-5-nitropyrazole. Probably it is related to the fact that nitro group in 1-methyl-3-nitropyrazole is located near electron-donative pyridine nitrogen atom (N-2). This is also the case for imidazoles l-methyl-4-nitro- and 1 -methyl-5-nitroimidazole. 

Photoelectron spectra (PE) experimental of some 4-nitropyrazoles, nitroimidazoles, [1119, 1405] and nitrobenzimidazoles [1193, 1406] have been recorded and interpreted in terms of semiempirical AM-1 method. PE spectroscopy is not a widely used method to study tautomeric equilibria in the gas phase although it can give excellent results. PE spectra data and 6-31G/6-31G calculations show that in the gas phase tautomers 4-nitro- and 5-nitroimidazole have the similar energy [1301], However in water, 4-nitroimidazole is much more stable (8AG°=3.5 kcal/mol >99% at 25°C.) than the 5-nitro tautomer. The authors [1301] show that this is conditioned by solvation effect. Probably it is connected with the large difference in dipole moments of the tautomers (see Table 3.72). 

With the help of 35C1 Nuclear Quadrupole Resonance (NQR) spectroscopy and AMI, MNDO h PM3 calculation data of tautomers of 2-trichloromethyl-5(6)-nitrobenzimidazole it is established that 5-nitro tautomer is more preferable than its 6-isomer (Scheme 3.76) [1407],... 

Method Angle 5-Nitro tautomer 6-Nitro tautomer ... 

Another way to study tautomerism is through p/iTa measurements. A comparison of the basic pATa values for 4(5)-nitroimidazole with those of l-methyI-4- (29) and l-methyl-5-nitroimidazole (30) leads one to the conclusion that the 4-nitro tautomer (28) predominates (Scheme 13) in fact the 4-nitro 5-nitro ratio has been computed as about 400 1. In this experiment the methylated compounds serve as fixed models in which the nitro substituent is fixed in each of the two possible orientations. The influence of the methyl group can be shown to be small by comparison of the pATa values for imidazole ( 7.0) and 1-methyl-imidazole ( 7.1), and hence l-methyl-4-nitroimidazoIe resembles the major tautomer. 

Because of the H bond in the 4(7) compound, there is a restricted tautomerism. The conjugated double bond arrangement is to some extent frozen in the 7-nitro tautomer shown in Fig. 5-5. The results... 

Ab initio calculations have shown that in nitroimidazoles the protonated 2- and 4-isomers are more stable (by 920 kJ mol ) than their conjugate bases (4- and 5-nitro tautomers have the same conjugate acid), and 4-nitroimidazolium is more stable than 2-nitroimidazolium by 29 kJ mol ... 

Schworer, M., Wirz, J., Photochemical Reaction Mechanisms of 2 Nitrobenzyl Compounds in Solution I. 2 Nitrotoluene Thermodynamic and Kinetic Parameters of the aci Nitro Tautomer, Helv. Chim. Acta 2001, 84, 1441 1458. 

Imidazoles with a ring iV-hydrogen are subject to tautomerism, which becomes evident in unsymmetri-cally substituted compounds such as the methylimidazole shown. This special feature of imidazole chemistry means that to write simply 4-methylimidazole would be misleading, for this molecule is in rapid tautomeric equilibrium with 5-methylimidazole. All such tautomeric pairs are inseparable and the convention used to cover this phenomenon is to write 4(5)-methylimidazole . In some pairs, one tantomer predominates, for example 4(5)-nitroimidazole favours the 4-nitro-tautomer by 400 1. 

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