Pyrazole Michael reactions

N-Unsubstituted pyrazoles and imidazoles add to unsaturated compounds in Michael reactions, for example acetylenecarboxylic esters and acrylonitrile readily form the expected addition products. Styrene oxide gives rise, for example, to 1-styrylimidazoles (76JCS(P1)545). Benzimidazole reacts with formaldehyde and secondary amines in the Mannich reaction to give 1-aminomethyl products. 

Michael reaction Catalyzed by HfCU, indoles and pyrroles undergo Michael reactions with enones at C-3, and C-2/C-5, respectively. The reaction of pyrazole and imidazole takes place at an N-atom. 

Pyrazole and its 3,5-dimethyl and 3,4,5-trimethyl derivatives combined with two moles of dimethyl acetylenedicarboxylate giving products of similar ultraviolet absorption spectra to the parent pyrazoles. These products [e.g., (69)] do not possess the strong broad absorption at ca. 3.20 /u, characteristic of the bonded N—H group which is present in the parent pyrazoles and are formed by two successive Michael addition reactions. In the case of 3,5-dimethylpyra-zole, the initial fumarate (68) has been isolated and possessed a more conjugated type of absorption spectrum to those of the dipyrazolyl-... 

The bispyrazolodihydropyran 435 was obtained directly as a rapidly formed insoluble by-product in the reaction of 3-methyl-l-phenylpyrazol-5-one 433 with activated nitriles 434 in the presence of catalytic piperidine (Equation 117) <2000MOL746, 2000JCCS937>. It is proposed that the reaction proceeds by loss of the active methylene moiety from the initial Michael adduct, allowing attack by a second molecule of pyrazol-5-one. 

The reaction of compound 98 with Michael acceptors such as acrylonitrile in the presence of pyridine gives a product which reveals to be the /3-(3-hydroazino-l,2,4-triazolo[3,4-A]benzothiazole)propanenitrile 203, which on reflux with hydrochloric acid underwent hydrolysis, followed by simultaneous cyclization, forming 3-(pyrazol-5-one-l-yl)-[l,2,4]triazolo[3,4-A]benzothiazole 204 (Scheme 10) <2004IJH241>. 

The Addition of the NH-Gtroup ofPyrazoles to Activated Double Bonds Pyrazoles undergo Michael addition to a,j3-unsaturated acids and esters,618,736,737,737 acrylonitrile,104,483,738 maleic anhydride, acetylene dicarboxylic ester,282,737 a,j8-unsaturated ketones,736 and quinones.104 Alkaline catalysts667 are not essential in this reaction,104 at least for addition to unsaturated nitriles, maleic anhydride, and quinones. The reaction is reversible, and V-pyrazolyl propionic... 

Polshettiwar V, Varma RS (2010) Nano-organocatalyst magnetically retrievable ferrite-anchored glutathione for microwave-assisted Paal-Knorr reaction, aza-Michael addition, and pyrazole synthesis. Tetrahedron 66 1091-1097... 

Elmaati and co-workers (03JHC481) (Scheme 59) heated 3-(3-oxopyrazol-4-yl)-3-oxopropionitrile 220 with readily available 2-dimethylaminomethylene-3-(phenylhy-drazono)-indan-l-one 221 in ethanol containing a catalytic amount of piperidine and isolated pyrazol-3-one derivative 224. The reaction is postulated to occur via initial Michael addition to give intermediate 222, elimination of dimethylamine to 223 followed by cyclization between the enolic OH and nitrile groups. 

The reaction of A -substituted pyrazoles with alkynic esters in the presence of fluoroboric acid yields Michael addition salts and not Diels-Alder adducts as was previously reported in the literature <83T2193>. Addition of 3,5-dimethyl-pyrazole to DMAD (dimethyl acetylenedicarboxylate) is highly stereoselective in aprotic solvents, yielding mono- and bis-adducts <85JCS(P2)427>. 

The synthesis of cahx[4]arene dimelamines with different functionalities and their self-assembly with barbituric and cyanuric acid to hydrogen-bonded nanostructures have been published <05OBC3727> Unique ionophores of penta-crown ethers have been prepared by the reaction of l,3,5-triacryloylhexahydro-l,3,5-triazine (TAHTA) with diaza 18-crown-6 followed by Michael addition, and their binding capabilities towards alkali metal cations studied <05SL2257>. New silver complexes of polydentate ligands including a derivative of pyrazol-l-yl-l,3,5-triazine have been reported <05EJ14370>. 

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