The application of vinylogous iminium salt derivatives to the regiocontrolled preparation of heterocyclic appended pyrazoles

Synthesis of Pyrazoles via Electrophilic Cyclization

“…In this reaction, pyrazole 25a formed in addition to 4-iodopyrazole 24a . As anticipated, during the formation of 24a , the reaction with iodine produces HI, which catalyzes the cyclization of hydrazone Z -22a to pyrazole 25a to some extent, consistent with the earlier findings. , On the other hand, the reaction of hydrazone Z -22a with molecular iodine in the presence of NaHCO 3 provided the highest yield (80%) of iodopyrazole 24a (Table , entry 4). Interestingly, iodocyclization was very fast at even room temperature and went to completion in almost 2 h. The same reaction in acetonitrile at room temperature or under reflux conditions did not improve the yield of 24a (Table , entries 5–7).…”

“…As anticipated, when hydrazinium salts are employed, the reaction medium becomes slightly acidic and pyrazoles are obtained in good yields. Apparently, acid catalyzes the reaction, but in this case, the reaction leads to formation of a mixture of pyrazoles 3 and 4 , consistent with the findings of other investigators using similar systems. , As previously noted, these reactions proceed through corresponding hydrazone and/or conjugated addition intermediates, depending upon the nature of the substituent in hydrazine derivatives 2 . , …”

Preparation of indole containing building blocks for the regiospecific construction of indole appended pyrazoles and pyrroles

“…1 H NMR analysis of the crude product indicated a mixture of 1,2- and 1,3-isomers with regard to the location of the phenyl and indolyl groups around the pyrazole ring system. Our research group 16 as well as others 17 have reported that the chemical shift differential between ortho pyrazole hydrogens is increased in polar NMR solvents for the 1,3-isomer versus the 2,3-isomer and applying this reasoning to our crude reaction 1 H NMR suggested an isomer ratio of 2:1 for the 1,3-isomer:2,3-isomer, respectively. The crude reaction mixture was then subjected to flash chromatographic purification on a Biotage SP-1 instrument with a silica column and hexane/ethyl acetate gradient.…”

“…Interestingly, when the reaction was repeated in the absence of base, two isomeric pyrazole products were indicated in the crude reaction mixture (Scheme 7). Our research group 16 and others 17 have reported that the chemical shift differential between ortho pyrazole hydrogens is increased in polar NMR solvents for the 1,3-isomer (chemical shift differential 1.45 Hz) relative to the 1,5-isomer (chemical shift differential 1.13 Hz). Applying this reasoning to our crude reaction mixture suggested an isomer ratio of 2:1 for the 1,3-isomer versus the 1,5-isomer, respectively.…”