Pyrazole ring electron-rich

Intramolecular addition of the amide group to the triple bond in pyrazoles is more difficult, and results in closure of the 5-lactam rather than the y-lactam ring. The reaction time of the 4-phenylethynylpyrazole-3-carboxylic acid amide under the same conditions is extended to 42 h (Scheme 129) (Table XXVII). The cyclization of l-methyl-4-phenylethynyl-l//-pyrazole-3-carboxylic acid amide, in which the acetylene substituent is located in the 7r-electron-rich position of the heterocycle, is the only one complete after 107 h (Scheme 130) (90IZV2089). 

For both cycles, a concerted mechanism is suggested in which the electron-rich double bond of the alkene attacks a peroxidic oxygen of 2. It has been inferred, from experimental data, that the system may involve a spiro arrangement [3, 5 a]. The selectivity toward epoxides can be enhanced by the addition of Lewis O- or Wbases such as quinuclidine, pyridine, pyrazole or 2,2 -bipyridine to the system [3, 6d, lOg-k]. Lewis acids catalyze ring-opening reactions and diol formation. These reactions are suppressed after the addition of Lewis bases. An... 

Another [3-i-2]-cycloaddition on carbon nanotubes may be performed with nitrile imines. In doing so, a pyrazole ring is formed on the tube s surface (Figure 3.74c). Upon choosing an appropriate substituent, an electron transfer from the electron-rich residue to the nanotube can occur. 

Some pyrazole rings are electron-rich enough to undergo the Friedel-Crafts reaction. With the aid of AICI3 as the Lewis acid, the pyrazole below underwent the Friedel-Crafls aroylation widi o-fluorobenzoyl chloride to afford the ketone, an advanced intermediate for the synthesis of novel potential antipsychotic agents. ... 

More recently, a study on the influence of the substituents in the reactivity of 1-aryl-3,5-substituted pyrazoles 22 in microwave-mediated fluorinations with Selectfluor at C-4 of the pyrazole ring was reported [13], In general, deactivated pyrazoles were unreactive or gave lower yields than more electron-rich derivatives (Scheme 8). Moreover, side products derived from fluorination of aryl or methyl substituents at N-1 and C-3 were isolated. Noteworthy, this was not the case at C-5, probably due to the steric interference between the substituent and the fluorine source. Results were compared with those obtained via C-2 fluorination of 1,3-diketones 21 followed by in situ condensation with arylhydrazines (see below). 

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