Pyrazole Mannich reaction

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. 

Pyrazoles and imidazoles exist partly as anions (e.g. 108 and 109) in neutral and basic solution. Under these conditions they react with electrophilic reagents almost as readily as phenol, undergoing diazo coupling, nitrosation and Mannich reactions (note the increased reactivity of pyrrole anions over the neutral pyrrole species). 

H,3H- Pyrrolo[l, 2-c]oxazole-l, 3-dione, 5,6,7,8-tetrahydro-IR spectra, 6, 978 [2.2](2,5)Pyrrolophane, N-aryl-rearrangements, 4, 209 Pyrrolophanes natural products, 7, 764 synthesis, 7, 771 Pyrrolophanes, N-aryl-synthesis, 7, 774 (2,4)Pyrrolophanes synthesis, 7, 771 Pyrrolo[3,4-c]pyran-4-ones synthesis, 4, 288 Pyrrolopyrans synthesis, 4, 525, 526 Pyrrolopyrazines synthesis, 4, 526 Pyrrolo[l, 2-a]pyrazines synthesis, 4, 516 Pyrrolo[2,3-6]pyrazines Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolo[3,4-c]pyrazole, 1,3a,6,6a-tetrahydro-structure, 6, 976 synthesis, 6, 1019 Pyrrolopyrazoles synthesis, 5, 164 Pyrrolo[l,2-6]pyrazoles synthesis, 6, 1002, 1006 Pyrrolo[3,4-c]pyrazoles reactions, 6, 1034 synthesis, 6, 989, 1043 Pyrrolo[3,4-c]pyrazolones synthesis, 6, 989 Pyrfolopyridazines synthesis, 4, 517 Pyrrolo[l, 2-6]pyridazines synthesis, 4, 297 6/7-Pyrrolo[2,3-d]pyridazines synthesis, 4, 291 2/f-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291 6/7-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291... 

Macrocycles 260 Mannich Reaction 19 MCR, pyrimidines/pyrazoles/isoxazoles 46... 

The hydrogen atom of the imino group of pyrazoles is sufficiently active to take part in Mannich reactions. Thus, pyrazoles unsubstituted on nitrogen, with formaldehyde and secondary amines, react smoothly to give high yields of dialkylaminomethyl derivatives (64) which are acid labile.653-656 Pyrazoles substituted on nitrogen give... 

Mannich reaction of A, A -bis(methoxymethyl)diaza-18-crown-6 with 4-chloro-2-(l/f-pyrazol-3-yl)phenol gave the N-linked bis(3-(5-chloro-2-hydroxy)pyrazol-l-ylmethyl)-substituted diazacrown ether, which interacted with various metal ions and was evaluated by calorimetric titration <1999JOC8855>. Intramolecular nitrilimine cycloadditions were exploited in the preparation of a number of azacrown ethers having a medium or large ring annulated to pyrazole units <1997T3005>. 

More recently formaldehyde or paraformaldehyde in the classical Mannich reaction has been replaced by methylene chloride. Reaction of pyrazol-3-one (antipyrine) 70 with dimethylamine or piperidine in methylenene chloride at 40 °C or with morpholine in a 1 1 v/v methylene chloride/acetonitrile mixture at 50 °C,... 

As reported by Mannich (29AP(267)699>, reaction of ethyl cyclopentanone-2-carboxylate with phenylhydrazine and subsequent cyclization of the phenylhydrazone at elevated temperature under strongly basic conditions gives tetrahydro-2-phenylcyclopentapyrazol-3-one (equation 19) (a = b = CH2). The method has been used to prepare thieno[3,4-c]pyrazol-3-ones, thieno[3,2-c]pyrazol-3-ones and pyrrolo[3,4-c]pyrazolones (71JMC454,71JMC1129). 

Phosphorus-containing Ring Systems. - A range of new chiral oxazaphospholidine oxides 266 and 267 have been synthesised and used as catalysts in asymmetric reductions of ketones with diborane. Mannich-type cyclisation reactions of 5-amino-3-benzylthio-4-cyano(ethoxycarbonyl)pyrazoles with dichlorophenylphosphine and aromatic aldehydes in the presence of cation exchange resin have been used to prepare a number of 6-oxo-6-phospha-4,5,6-trihydroimidazolo[l,2-b]pyrazoles, e.g. 268. Some of these compounds have herbicidal activity and this report is typical of a number of similar ones in the Chinese literature. A number of metallocycles, e.g. 269, have been reported as products from reactions of transient zirconocene-benzyne intermediates with phosphaimines followed by sulfuration or selenation. ... 

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