Uncatalyzed One-Pot Synthesis of Highly Substituted Pyridazines and Pyrazoline-Spirooxindoles via Domino SN/Condensation/Aza-ene Addition Cyclization Reaction Sequence

Abstract

A previously unknown class of highly substituted pyridazines and pyrazoline-spirooxinoles are easily prepared by an uncatalyzed one-pot three-component approach incorporating a domino SN/condensation/aza-ene addition cyclization reaction sequence. 1,1-Dihydrazino-2-nitroethylene (DHNE) which is generated in situ from the nucleophilic substitution (SN) reaction of hydrazine and 1,1-bis(methylthio)-2-nitroethylene (BMTNE), allowed to be condensed with active 1,2-dicarbonyl compounds followed by an intramolecular aza-ene addition cyclization to obtain the titled products depending on the type of 1,2-dicarbonyl. All reactions are easily performed and proceed with high efficiency under very simple and mild conditions without any catalyst and give good yields avoiding time-consuming, costly syntheses, and tedious workup and purification of products.

Synthesis of spiro-fused heterocyclic scaffolds through multicomponent reactions involving isatin

“…1,1-Dihydrazino-2-nitroethylene 275, which was generated in situ from the nucleophilic substitution reaction of hydrazine 130 and 1,1-bis(methylthio)-2-nitroethylene 269, was isolated and allowed to condense with isatins 1 followed by an intramolecular aza-ene addition cyclization (Scheme 112). 206 A pseudo-fivecomponent reaction was also used in similar condition for the synthesis of the same products. This procedure avoided the isolation of the intermediate 275.…”

Crystal structure of 8-[7,8-bis(4-chlorobenzoyl)-7H-cyclopenta[a]acenaphthylen-9-yl]naphthalene-1-carboxylic acid

“…In this reaction, multiple C-C or C-H bonds are formed in the same vessel, including different reaction mechanisms to form complex molecules without the purification of intermediates. These reactions are often used in medical or combinatorial chemistry to synthesize complex active drug molecules (Sudhapriya et al, 2014;Tietze et al, 2014;Fu et al, 2013;Shestopalov et al, 2013;Zohreh & Alizadeh, 2013;Renault et al, 2007). Domino reactions are classified as homo-domino processes and hetero-domino processes (Nesi et al, 1999).…”

Highly efficient, catalyst‐free, one‐pot, pseudo five‐component synthesis of novel pyrazoline‐containing Schiff bases, metal complexes formation and computational studies via DFT method

“…Pyrazolines are very important five‐membered heterocyclic compounds, which are found as the central structure in a wide range of compounds that possess extensive bioactivities including antimicrobial, anticancer, anticonvulsant, antiviral, antitumor, anti‐inflammatory, and antifungal activities . Although some methods have been reported for the preparation of pyrazoline, most of these strategies suffer from various disadvantages such as low yields, low functional group tolerance, catalyst application, and tedious workup procedures. Recently, Alizadeh et al developed a novel synthesis of pyridazines and pyrazoline‐spirooxindoles by using 1,1‐dihydrazino‐2‐nitroethylene (DHNE) as a primary diamine.…”

“…Although some methods have been reported for the preparation of pyrazoline, most of these strategies suffer from various disadvantages such as low yields, low functional group tolerance, catalyst application, and tedious workup procedures. Recently, Alizadeh et al developed a novel synthesis of pyridazines and pyrazoline‐spirooxindoles by using 1,1‐dihydrazino‐2‐nitroethylene (DHNE) as a primary diamine. Based on our research, literature reviews revealed no other report on the application of DHNE.…”