Pyrazole formation

Dimethylaminopyrazoles react with alkylating agents to afford quaternary salts (72BSF2807). The nitrogen atom of the dimethylamino group is the most reactive in the case of 3-dimethylamino- and 4-dimethylamino-pyrazoles (formation of 456 and 457 salts, respectively) whereas 5-dimethylaminopyrazoles yield aminopyrazolium salts (458). 

A recent paper by Singh et al. summarized the mechanism of the pyrazole formation via the Knorr reaction between diketones and monosubstituted hydrazines. The diketone is in equilibrium with its enolate forms 28a and 28b and NMR studies have shown the carbonyl group to react faster than its enolate forms.Computational studies were done to show that the product distribution ratio depended on the rates of dehydration of the 3,5-dihydroxy pyrazolidine intermediates of the two isomeric pathways for an unsymmetrical diketone 28. The affect of the hydrazine substituent R on the dehydration of the dihydroxy intermediates 19 and 22 was studied using semi-empirical calculations. ... 

Ring closure of vinyldiazo compounds to 3/7-pyrazoIes is a thermally allowed process that competes with carbene formation via loss of N251 (see also Section IV,A,2). In a kinetic study it was shown that electron-withdrawing aryl substituents attached to the diazo carbon atom favor 3H-pyrazole formation.98 The cyclization of 47 to 48 at - 15°C (Scheme 15) is almost quantitative.91... 

Bisdiazopropane slowly decomposes in cyclohexene solution, in the dark, to yield Nj, pyrazole and a small amount of polymer . At 25° the first-order rate coefficient expressed in terms of pyrazole formation, was 9.8 x 10 sec and... 

In some instances there may be competition between 5- and 6-membered ring formation, for example in the condensation of hydrazine in acetic acid with 3-(substituted-benzoyl)-3-butenoic acids, pyrazole formation dominates and the pyridazinone products are formed in very low yields <90JHC205>. Cyclization of the 1,4-diketone (118) was shown to be temperature dependent (Scheme 97, R = 4-carbomethoxy-2,3-dichlorophenyl). Thus in ethanol at room temperature with hydrazine hydrate the pyridazine (119) was produced, but when the reactants are heated under reflux in ethanol then the aminopyrrole (120) is formed instead <92AP(325)13>. However, even when alternative modes of cyclization might be expected they may not be observed, as in the case of the reaction of 4-aryl-... 

Pyrazoles, - Formation. A mixture of the pyrazoles (242) and (243) is produced by thermolysis of the azines PhCH=CHCH=NN=CMeCH=CHAr. The reaction of diazodibenzoylmethane with 1-diethylaminopropyne,... 

Pyrazoles.- Formation During the formation of 3,5-dimethylpyrazole from acetyl-... 

Pyrazole formation is an intramolecular 1,3-dipolar cycloaddition 3-diazopro-pene is, however, also a 1,5-dipole in the sense of Huisgen s Schemes 6-5 and 6-6, i.e., a compound with a potential diazonio group (6.120 —N=N = —b = a see discussion by Huisgen, 1980). 

Pyrazoles.—Formation. 3-Amino-4-ethylthio-5-methylpyrazole (311) is formed by the action of hydrazine on the nitrile MeBrC=C(SEt)CN. Acetylenic hydrazones R C=C-C(R )=NNHTos (R = H, Pr, or Ph R = H or Me) cyclize in the presence of potassium carbonate to the pyrazoles (312) via the iV-tosyl derivatives. Treatment of the (p-chlorophenyl)hydrazone (313) of ethyl 2-furylpyruvate with sulphuric acid affords only 10% of the expected ethyl 3-(2-furyl)indole-2-carboxyIate the main product is the pyrazole (314), formed presumably by way of the spiro-intermediate shown. ... 

Generic companies attempted to develop process routes to make rimonabant without infringing on Sanofi s patents. For example, an improved process was developed by taking advantage of a trivial fact that sulfuric acid could promote pyrazole formation and hydrolysis of the ethyl ester simultaneously. ... 

Methoxyimino-ketones are not only variants of the 1,3-dicarbonyl group, but also they have the advantage of affording excellent regioselectivity for the pyrazole formation. Chemoselective condensation between the diketoester and methoxyamine hydrochloride produced... 

The 1,3-dipolar cycloaddition between diazoalkanes and alkynes resulting in pyrazole formation is known as the Pechmann pyrazole synthesis. ... 

Pyrazole formation is likely to occur via hydrazone formation (—>20) and cyclization by intramolecular NH-addition to the cyano group (—>21) concluded by tautomerization —>19). A solid-phase-catalyzed version (montmoriUonite K-10) was reported [436] as well as the use of acetylhydrazine for minimizing side reactions and removal of the acetyl group by N-methylpiperazine [437]. 

Fustero S, Roman R, Sanz-Cervera JF, Sim6n-Fuentes A, Bueno J, ViUanova S (2008) Synthesis of new fluorinated tebufenpyrad analogs with acaricidal activity through regiose-lective pyrazole formation. J Org Chem 73 8545-85552... 

Furthermore, the pyrazole formation reaction was also combined with a palladium-catalyzed Sonogashira coupling with a terminal alkyne and subsequent intramolecular 6-endo alkyne hydroamination to provide an alternative approach to the facile synthesis of pyrazolo[5,l-a]isoquinoline 36 (Scheme 7.19) [72]. 

Pyrazoles.—Formation. Butadiyne reacts with methylhydrazine to yield either 1,3-dimethylpyrazole (407) or the 1,5-isomer, depending on conditions. 2,2-Diacylketen 55-dimethyl acetals and related compounds yield methylthio-pyr-azoles on treatment with hydrazine thus compound (408) gives the ketone (409), ° and the nitrile (410) gives the amine (411), The azine (412) is converted into the pyrazole (413) in refluxing xylene the reaction involves... 

Obviously, the reason is configuration of 2-(l-ethylthio-2-carbamoyl-2-cyanovinyl)pyrrole stabilized by intramolecular H-bond, which is favorable for the pyrazole formation. 

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