Substituent chain tautomerism

Pyrazol-5-ones are widely used in medicine, color photography, analytical chemistry, and agriculture. The tautomeric equilibria between the CFI, OH, and NH forms in a series of 4-substituted-l-phenyl-3-methyl-pyrazolin-5-ones 100-102 have been studied using ab initio calculations at various levels of theory and comparison made with the experimental results obtained from C NMR measurements 2001JP0566 . The tautomerism of 4-acyl-2-phenyl-2-pyrazolidin-3-ones 103 and 104 was studied by C NMR spectroscopy 1999CHE748 . The tautomerism of 

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Thiol-thione tautomers have not been extensively studied, but UV and IR evidence show that 5-phenylisothiazole-3-thiol exists in the SH form. Ring-chain tautomerism of 2,3-dihydro derivatives of 1,2-benzisothiazole can occur (26a 26b) and the position of equilibrium depends very much on the solvent, physical state and nature of the substituents (69JOC919, 81KGS1209). 

The ring-chain tautomerism of the imidazolidines 279 (80H1313) is of interest (Scheme 99). The isomer ratio is determined by the nature of the substituents and is hardly affected by the polarity of the solvent (CCI4, DMSO). 

Ring-chain tautomerism was observed in a series of l,2,3,6-tetrahydro-l,2, 4-triazine 4-oxides 5 in nonpolar solvents (e.g., CCI4) by NMR spectroscopy. Depending on the nature of substituents R and R, the ratios of the cyclic form of 1,2,4-triazine 5a to the open-chain form of hydrazone 5b were found to be up to 45 55 (77ZOR2617). 

Talancon et al.40 investigated the effects of substituents on the ring-chain tautomerism of Schiff bases being derivatives of norephedrine on the basis of 1H and 13C NMR measurements [19]. 

However, the introduction of sterically hindered substituents at the p-car bon atom of nitroalkene (42) completely changes the ring-chain tautomerism of conjugated nitroalkenes. Apparently, steric hindrance caused by two bulky Bu groups in product (42a) (Scheme 3.47) prevents effective conjugation of the jt systems of the C,C double bond and the nitro group, thus causing its deviation from the plane of the C=C bond as a result of which isomer (47a) becomes thermodynamically more favorable. 

The formation of five-membered cyclic nitronates (404) is explained in terms of ring-chain tautomerism of cationic intermediates A (A=A ). The presence of the alkoxy substituent (R4) at the C-6 atom could stabilize the open form (cation A7), which finally leads to the formation of functionalized five-membered cyclic nitronates (404) probably with the participation of water. 

The iV-unsubstituted 2-aryltetrahydro-l,3-oxazines exhibit ring-chain tautomerism in solution. Depending on the steric and electronic characters of the substituents, the ring form and the open-chain Schiff base form occur in different ratios. For a more detailed discussion, see Section IV,A,4. 

The ring-chain tautomerism of tetrahydro-l,3-oxazines is very sensitive to the stability differences, the substituents and the ring-fusion effect (Section IV,A). It also reveals a considerable stability difference in favor of the cis isomers. In the reactions of the cis- and trans-2-amino-l-cyclohexanols, as compared with the hydrindane analog systems, where the heteroatoms form an oxazolidine ring cis- or tra 5-fused with cyclohexane, the corresponding stability differences were again found to be in favor of the cis isomer (93JOC1967). 

To characterize the electronic and steric effects of the substituents at positions 4-6 on the stability of the 2-aryl-l,3-oxazine ring forms exhibiting ring-chain tautomerism, a relative ring stability parameter (c) has been introduced. The value of c is calculated as the difference between the value of log Xx = h for a 2-aryl-l,3-oxazine derivative bearing substituents at positions 4-6 and the intercept value (log Xo = —0.15) for the parent unsubstituted 2-arylperhydro-l,3-oxazine (c = log Xx = h log Xq). 

Aryl substituents on the 1,3-oxazine ring give rise to a characteristic effect on the two- or three-component ring-chain tautomeric equilibria of 2,3-dihydro-l//-naphth[l,2-< ][l,3]oxazines 35-44 and the regioisomeric 3,4-dihydro-2//-naphth[2,l-H[l,3]oxazines 45-51 (Scbeme 6). The major ring forms of the equilibria 36-51 contain the 1,3- or... 

The electronic effect of the substituent X on the 2-phenyl ring proved to influence the ring-chain tautomeric equilibria of 2-aryl-l-hydroxy-l,4-dihydro-2//-3,l-benzoxazines 79. While the proportion of the cyclic tautomer B in CDCI3 was 90% for the unsubstituted (X = H) and 70% for the />-methoxy derivative (X = OMe), no cyclic form could be detected in the case of the -dimethylamino compound (X = NMc2). Independently of the substituent X, the tautomeric equilibria of the regioisomeric 2-aryl-3-hydroxy-3,4-dihydro-2//-l,3-benzoxazines likewise contained no detectable amounts of the cyclic forms <1997CJC1830, 1998CJC389>. 

Methyl hydrazones of a wide range of aldehydes and ketones (380) undergo addition-cyclization to give 1,2,4,5-tetrazines (382) via 381 (216-219). Substituent effects on the ring-chain tautomerism between 381 and 382 were studied by NMR spectroscopy. 

Ring-chain tautomerism can occur when a substituent group can interact with an NH group or nitrogen atom of a heterocyclic ring. 

All known examples of ring-chain tautomerism can be conveniently divided into two large groups (i) those without direct involvement of any substituent in the heterocyclic ring and (ii) isomerizations with participation of certain substituents. 

Another example of ring-chain tautomerism with participation of a substituent is the interconversion of furoxan-2- and furoxan-5-oxides (104a 104b). The equilibration is presumed to proceed via an intermediate cis- 1,2-dinitrosoalkene (105). In the benzofuroxan series the involvement of the corresponding 1,2-dinitrosoarenes as intermediates has been firmly established by matrix isolation experiments (91CC1178, 91JOC5216,92CL57). 

Boiling points and melting points are considered from the point of view of intermolecular forces between the molecules, together with solubilities and chromatographic behavior, both gas and liquid chromatography. The topic of aromaticity and stability in general is covered as befits its importance. Conformations, particularly of the cyclic non-planar compounds, are dealt with. A section on tautomerism covers both prototropic tautomerism (annular and of substituents) and ring-chain tautomerism. 

The solvent, temperature, and substituent (R and R1) -dependent ring-chain tautomerism of 2-pyridylaminomethylenemalononitriles (167 168) was studied (86JOC2988). 2-Pyridylaminomethylenemalo-nonitriles were prepared in the reaction of 2-aminopyridines and 2-(l-ethoxyalkylidene)malononitrile in ethanol at room temperature or in a melt at 120°C, and in a one-pot reaction, starting from 2-aminopyridines, a triethyl orthoester, and malononitrile at 110°C for 10 minutes. The content of the equilibrium mixture of 2-pyridylaminomethylenemalononitrile 167 (R = R1 = H) is shown in Table X. Elevation of the temperature increased the proportion of the chain tautomer. The ratio between the two tautomeric forms 167 and 168 is influenced primarily by the steric properties of substituents R and R1 in positions 6(6) and 3(9), respectively,... 

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