Maleic hydrazide, tautomerism

Phthalic hydrazide has received even more attention than maleic hydrazide, the potential tautomerism having been discussed since 1925. Chemical evidence has been advanced both for the dioxo form and for the dihydroxy form 89, and it has been fur-... 

Molecules in real solvents can exist in one or more tautomeric forms. The use of different tautomers in calculations can lead to significant variation in the estimated log P values (Pig. 15.1). Accurate prediction of the dominant tautomer requires ah initio calculahons. Due to speed limitations such calculations are not feasible for virtual screening and prediction of large compound collections. Moreover, the interpretation of the results can also be difficult, for example, the lacton-lactim (Pig. 15. IB) is the stable form of maleic hydrazide in the gas phase but the difference between this and the dilacton form (Pig. 15.1C and D) disappears in solution... 

Fig. 15.1 Different tautomeric forms, dilactim (A), lacton-lactim (B) and dilacton (C and D), of maleic hydrazide (CAS-RN 123-33-1), log P = -0.56 (-0.84 in the BioByte StarList [10]).

When two amide groups in a six-membered aromatic ring are in opposition to each other, as in maleic hydrazide, the oxo structure [143] is not so highly stabilized and tautomerism is observed in which the 6-hydroxy-3-pyridazone form [144] predominates (Katritzky and Lagowski, 1963). The p/fj-value of this compound is... 

Calculations have been applied to the problem of tautomerism of maleic hydrazide and other pyridazinones. The lactam structure was found to be the most stable, but in the case of 3-amino-4-hydroxypyridazine the aminol form is energetically most favorable. ... 

The wideline NMR, IR, and Raman spectra of maleic hydrazide were determined and discussed in connection with its tautomeric forms. NMR techniques have been used to predict the structure of cyclization products from 3-carboxyacryloylhydrazines. The NMR spectra of JV-methyl-pyridazinium iodides and pyridazine iV-oxide were investigated, and the... 

Applying the synthetic principle (1) (see p 395), pyridazine itself can be prepared from maleic anhydride. Its reaction with hydrazine yields maleic hydrazide 18 which is converted with POCI3/PCI5 into 3,6-dichloropyridazine 19 due to an azinone-hydroxyazine tautomerism (see p 310) 19 gives rise to pyridazine by reductive dehalogenation with H2/Pd-C ... 

Tautomeric Ratios Requiring Computation "Maleic Hydrazide"... 

Maleic hydrazide 34, 3,6-dihydroxypyrazine, has proved to be one of the most difficult tautomeric systems to investigate experimentally [20]. It is useful to start, however, by discussing the apparently parallel case of uracil 31 [21] since this will help to bring out the underlying problem. Data for uracil appear in Figure 2.7. 

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