Thiamine Hydrochloride–Catalyzed One-Pot Synthesis of 1,4-Dihydropyridine Derivatives Under Solvent-Free Conditions

Abstract

An efficient one-pot synthesis of 1,4-dihydropyridines from an aldehyde, β-keto ester, and ammonium acetate or formamidine acetate using thiamine hydrochloride (VB₁) as the catalyst under solvent-free conditions at ambient temperature is described. All types of aldehydes, including aromatic, aliphatic, and unsaturated aldehydes, give good yields. The catalyst can easily be recovered after completion of the reaction and reused without affecting its activity.

Keywords:

• Aldehydes
• 1,4-dihydropyridines
• Hantzsch reaction
• β-keto ester
• thiamine hydrochloride (VB₁)

ACKNOWLEDGMENTS

This work was supported by the Chinese National Science and Technology Major Project, “Key New Drug Creation and Manufacturing Program” (Grants 2009ZX09301-001 and 2009ZX09102), the Chinese National High-Tech R&D Program (Grants 2007AA02Z147), the National Natural Science Foundation of China (Grants 90713046, 30772638, and 30925040), and the CAS Foundation (Grant KSCX2-YW-R-179).

Notes

^a Conditions: propionaldehyde 1a (5 mmol), ethyl acetoacetate 2a (10 mmol), ammonium acetate (10 mmol), solvent 5 mL or solvent free, at ambient temperature.

^b Isolated yield.

^c Catalyst was reused three times.

^a Conditions: propionaldehyde 1a (5 mmol), ethyl acetoacetate 2a (10 mmol), and ammonium acetate (10 mmol), at ambient temperature.

^b Isolated yield.

^a Conditions: aldehyde 1 (5 mmol), β-keto ester 2 (10 mmol), ammonium acetate (10 mmol), and VB₁ (0.15 mmol, 3 mol %).

^b Isolated yield after 40 min.

^a Conditions: aldehyde 1a (5 mmol), ethyl acetoacetate 2a (10 mmol), formamidine acetate 6 (7.5 mmol), and VB₁ (0.15 mmol, 3 mol%), 80 °C.

^b Isolated yield after 30 min.