Synthesis of Pyrazoles via Electrophilic Cyclization

Abstract

Electrophilic cyclizations of α,β-alkynic hydrazones by molecular iodine were investigated for the synthesis of 4-iodopyrazoles. α,β-Alkynic hydrazones were readily prepared by the reactions of hydrazines with propargyl aldehydes and ketones. When treated with molecular iodine in the presence of sodium bicarbonate, α,β-alkynic hydrazones underwent electrophilic cyclization to afford 4-iodopyrazoles in good to high yields. Iodocyclization was general for a wide range of α,β-alkynic hydrazones and tolerated the presence of aliphatic, aromatic, heteroaromatic, and ferrocenyl moieties with electron-withdrawing and electron-donating substituents.

Facile synthesis of alkynyl‐, aryl‐ and ferrocenyl‐substituted pyrazoles via Sonogashira and Suzuki–Miyaura approaches

“…We first prepared the required 4‐iodopyrazoles 5 and 6 from the corresponding propargyl aldehydes 1 and 2 according to our previous study as shown in Scheme . The neat reaction of ferrocenylpropargyl aldehyde ( 1 ) with phenylhydrazine at 80 °C afforded Z and E isomers of hydrazone 3 in 54 and 36% yields, respectively.…”

“…When reacted with molecular iodine, Z and E isomers of hydrazone 3 afforded ferrocenyl‐substituted 4‐iodopyrazole 5 in 90 and 92% yields, respectively. Iodocyclization of Z isomer of hydrazone 4 produced phenyl‐substituted 4‐iodopyrazole 6 in 80% yield (Scheme ) …”

“…All glassware was dried in an oven prior to use. The starting 4‐iodopyrazoles 5 and 6 were synthesized according to a previous study …”

“…Recently, we have reported the synthesis of α,β‐alkynic hydrazones 3 and 4 from propargyl aldehydes 1 and 2 , and their regioselective conversion into pyrazoles 5 and 6 , respectively (Scheme ) . When treated with molecular iodine in the presence of sodium bicarbonate, α,β‐alkynic hydrazones 3 and 4 undergo electrophilic cyclization and afford ferrocenyl‐ and phenyl‐substituted 4‐iodopyrazole derivatives 5 and 6 , respectively, in high yields.…”

4.07 Electrophilic Cyclization

“…84 Electrophilic cyclizations of a,b-alkynic hydrazones by molecular iodine afford synthesis of 4-iodopyrazoles in good to high yields (Scheme 78). 85 Wu and coworkers have described a highly efficient electrophilic cyclization of N 0 -(2-alkynylbenzylidene)-hydrazide with I 2 , Br 2 , or ICl in DCM at room temperature. It provides an efficient method to construct functionalized isoquinolinium-2-yl amides (Scheme 79).…”