Environmentally Benign Lewis Acid Promoted [2+3] Dipolar Cycloaddition Reactions of Nitrile Imines with Alkenes in Water

Abstract

Mild and environmentally benign Lewis acid promoted 1,3-dipolar cycloaddition reactions of α-hydrazonyl chlorides with alkenes in water are reported. These α-hydrazonyl chlorides, in the presence of Lewis acids, generate nitrile imines in situ which react with dipolarophiles to furnish the corresponding cycloaddition products. In many cases, the required times for the completion of the Lewis acid promoted 1,3-dipolar cycloaddition reactions in water were comparable to the equivalent reactions performed in an organic solvent. Analogous tetrahexylammonium chloride promoted 1,3-dipolar cycloaddition reactions were also performed. The comparison of reaction times and cycloadduct yields for the aforementioned 1,3-dipolar reactions in aqueous and organic media as well as the proposed role of the Lewis acid in the 1,3-dipolar cycloaddition reaction are described.

Copper(II) Sulfate

“…It is possible to generate spiro-pyrazolines by reacting hydrazonyl chlorides with alkenes in the presence of a stoichiometric amount of CuSO 4 in pure water at room temperature. 83 Among the various Lewis acids that were tested, CuSO 4 is one of the most efficient (eq 56). It is possible to synthesize quinoline-4-carboxylic acid derivatives by a CuSO 4 -catalyzed Pfitzinger reaction.…”

Synthesis and tautomerism of spiro-pyrazolines

“…5,6d,7g,13,14 In addition to methodology development, we are also equally interested in assessing structural and biological applications for spiro-pyrazolines. Recently, we demonstrated the construction of 1,3,5-trisubstituted pyrazoles on the basis of the 1,3-dipolar cycloaddition protocol, which was then followed by an unforeseen ring fragmentation/elimination.…”

A Study of [3+2] Cycloaddition Reaction of Hydrazonoyl Chloride and β‐Oxodithioester Under Lewis Acid Catalysis: Stereoselective Synthesis of (Z)‐1,3,4‐Thiadiazol‐2(3H)‐Ylidenes.

“…In the presence of a base, hydrazonoyl chlorides convert into nitrilimines, which are highly reactive 1,3‐dipoles [2] and participate in 1,3‐dipolar cycloaddition reactions with a variety of dipolarophiles such as alkenes, alkynes, carbonyls, thiocarbonyls, nitriles etc ., to give five membered azaheterocycles as shown in Scheme 1. In literature, however, similar 1,3‐dipolar cycloaddition reactions of nitrilimines are also known under acid catalysis and the examples are: i) synthesis of spiropyrazoles by reaction of nitrilimines with alkenes under copper nitrate catalysis [3] and ii) Preparation of dihydropyrazoles by reaction of nitrilimines with alkenes using magnesium bis(trifluoromethanesulfonimide) as a catalyst [4] . In both these reactions, alkenes are dipolarophiles and similar studies with other dipolarophiles such as C=S under acid catalysis are so far not reported in literature.…”