4- Substituted 5-hydroxypyrazol-3-ones

The problem of tautomerism is simpler in the case of 1-substituted pyrazolin-3-ones since only two forms, the OH (140a) and the NH (140b), are possible. The OH form is the more stable and is the only one present in the crystal (Section 4.04.1.3.1). In protic solvents, like water or methanol, the equilibrium position is much more evenly balanced between the OH and NH forms. Finally, 4-hydroxypyrazoles (141) exist as such. A CNDO/2 calculation justifies the result that 4-hydroxy tautomers are relatively more stable than... 

The biselectrophilic reactivity motif of alkynones is also present in 3-substituted alkyl propiolates 2. Utilizing the previously described Michael addition/cyclocondensation approach with various binucleophiles allows the introduction of oxo/hydroxyl substituents to the heterocycle. An example of the concept is the copper(I)-catalyzed carboxylation of terminal alkynes, which allows the convenient synthesis of 3-substituted alkyl propiolates 2 a by trapping the intermediary carboxylate with methyl iodide. This one-pot procedure can be expanded to a three-component process by adding binucleophiles such as amidines 36 and hydrazines 20 to furnish the corresponding 2,6-disubstituted pyrimidin-4(3fl)-ones 54 and 1,5-disubsti-tuted 3-hydroxypyrazoles 55 in a one-pot fashion. The incorporation of nontoxic, abundant and economical carbon dioxide provides an environmentally benign access to interesting heterocyclic structures (Scheme 33) (2014ASC(356)3135). 

Both compound classes can be obtained in moderate to good yields. In the case of 2,6-disubstituted pyrimidin-4(3fl)-ones 54 electroneutral and electron-rich amidine hydrochlorides 36 are favorable as well as electroneutral and electron-deficient terminal alkynes 5. For the synthesis of the 1,5-disubstituted 3-hydroxypyrazoles 55 alkyl-substituted hydrazine hydrochlorides 20 generally provide higher yields. 

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