Importance of aromaticity on the relative stabilities of indazole annular tautomers: an ab initio study

Abstract

MP2-6-31G** calculations on 1H-and 2H-indazole annular tautomers show that the 1H tautomer is more stable than the 2H one by 3.6 kcal mol-l. In the case of 1H-indazole, the excellence of MP2-6-31G** results is confirmed by the fact that its microwave rotational constants are reproduced with great accuracy. The addition of the thermal energy correction and entropy effects to AE(MP2-6-31G**) led to the following thermodynamic values: AIPg8( 1 H --+ 2H) = 3.9 kcal mol-l and AGG,298( 1 H + 2H) = 4.1 kcal mol-l. Electronic spectra recorded at 80 O C provided experimental evidence for the clear predominance of 1 H-indazole in the gas phase. Paper 5/03802B

On the solvatochromism, dimerization and tautomerism of indazole

“…that the dipole moment is nearly doubled upon excitation to the first excited singlet). Although 1H↔2H tautomerism of indazole in the ground state was previously ruled out , [9][10][11][12] according to Hirota et al it occurs in the first triplet state of the indazole -benzoic acid complex, 14 and in the first excited singlet of the indazole -acetic acid complex. 15 They ascribed both instances of tautomerism to a double proton transfer in the complexes.…”

“…2 The fact that these two nitrogen sites are located in adjacent positions in the molecular structure (see Scheme 1) allows indazole at low concentrations in mildly acid or basic media to form 1H and 2H tautomers via acid-base interactions (see Scheme 1), [3][4][5][6][7][8][9][10] as well as symmetrical dimers by hydrogen bonding. …”

Tautomerism and the Mills-Nixon-like effect in pyrazoles

“…Obviously there is an important anomaly concerning compound 10, for which a value of AE = +0.3 to +0.4 kcal mo1-1 was expected from its geometry instead of -1.65 kcal mol -~. A possible explanation is that the 6-31G* calculations take into account the antiaromaticity of the planar dehydrocyclooctatetraene ring and this strongly destabilizes tautomer 10a, overcoming the MNI effect; the situation should be the opposite to that of indazole 14, where the equilibrium is dominated by the aromaticity of tautomer 14a [16].…”

Five‐Membered Heterocycles: 1,2‐Azoles. Part 1. Pyrazoles

“…Note that the 15 N chemical shifts are very sensitive to hydrogen bonds and, obviously, to protonation. ) 3524 (n NH gas) [4] Source: [11] X-ray (CSD) [12] PYRZOL INDAZL 1 H NMR Source: [13] Source: [13,14] 13 C NMR Source: [15] Source: [16] 15 N NMR Source: [17] Source: [ Source: [22] Source: [23] Best theoretical calculations Source: [24] Source: [25] Aromaticity (benzene ¼ 0.991) 0.900: [26] 0.808: [26] a) a) Naphthalene: 0.811, 2H-indazole: 0.792 (using as criteria the HOMA) [27]. 111.9 NMR information on the non-aromatic derivatives of pyrazoles is very abundant, particularly on D 2 -pyrazolines and on pyrazolones [4,7].…”

“…The discovery of a second, inducible form of cyclooxygenase (COX-2) that exists along with the constitutive form (COX-1) led to the hypothesis that selective inhibitors of COX-2 would be anti-inflammatory without causing the side effects associated with inhibition of COX-1 in the gastrointestinal tract and kidney. This is the moment most promising approach at present and has ultimately led Searle to SC-58125 (25) and then to celecoxib SC-58635 (26) (MI 1968), which is useful for the treatment of rheumatoid arthritis and osteoarthritis [59]. Other pharmaceutical companies have explored this avenue; for instance Fujisawa has developed 27 [60].…”