Synthesis of C2‐Formamide(thiophene)pyrazolyl‐C4'‐carbaldehyde and their Transformation to Schiff's Bases and Stereoselective trans‐β‐Lactams: Mechanistic and Theoretical Insights. Issue 37 (4th October 2022)

• Record Type: Journal Article
• Authors: Saini, Preety; Bari, Shamsher S.; Yadav, Pooja; Khullar, Sadhika; Mandal, Sanjay K.; Bhalla, Aman
• Is Part Of: ChemistrySelect. Volume 7:Issue 37(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-04
• Subjects: Dual Carbaldehyde -- Schiff's Base -- Stereoselective trans-β-lactam -- Thiophene -- Vilsmeier-Haack reagent; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202202172
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Herein, we describe synthesis of functionalized thiophenyl acetyl‐hydrazones using acetyl‐thiophene derivative as precursor which further underwent Vilsmeier‐Haack reaction in an unexpected manner, providing three‐carbon atoms to the molecular framework. The mechanistic view explained formation of C2 ‐formamide(thiophene)pyrazolyl‐ C4 '‐carbaldehyde by three consecutive actions in single‐pot: 1) nucleophilic amino to C2 ‐iminium ion generation, 2) cyclization to pyrazole ring and 3) nucleophilic attack by pyrazole to C4 '‐iminium ion which finally leads to dual formylation in the system. This product burst to primary amines to synthesize highly substituted C2 ‐formamide(thiophene)pyrazolyl‐ C4 '‐Schiff's bases. Further, the reactivity of synthesized Schiff's bases underwent metal‐free ring closure with diverse heteroatomic ketene sources which exposed the emergence of stereoselective trans ‐β‐lactams. The broad functional groups encircled monocyclic β‐lactams were achieved in moderate to excellent yields under gentle conditions. Additionally, theoretical calculations on B3LYP/6‐31G(d, p) level of some representative compounds are also investigated to support mechanistic explanation with their stabilized structures and physical properties. Abstract : Synthesis of C2 ‐formamide(thiophene)pyrazolyl‐ C4 '‐carbaldehyde was achieved in a single vessel by precursor thiophene acetyl‐hydrazone, reacting with Vilsmeier‐Haack reagent, which provide three carbon atoms to the molecular framework at the end and exhibited dual formylation. The C4' ‐formaldehyde responds to primary amines rapidly and corresponding imines were accomplished. These set of Schiff's bases employed for various O/S/Se/CH3 COO encapsulated ethanoic acids and delivered a set of stereoselective trans‐ β‐lactams.