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. 2021 Oct 1;6(40):26035-26047.
doi: 10.1021/acsomega.1c02976. eCollection 2021 Oct 12.

1,3-Bis(carboxymethyl)imidazolium Chloride as a Sustainable, Recyclable, and Metal-Free Ionic Catalyst for the Biginelli Multicomponent Reaction in Neat Condition

Prabhakara Madivalappa Davanagere  1 , Barnali Maiti  1
Affiliations

1,3-Bis(carboxymethyl)imidazolium Chloride as a Sustainable, Recyclable, and Metal-Free Ionic Catalyst for the Biginelli Multicomponent Reaction in Neat Condition

Prabhakara Madivalappa Davanagere et al. ACS Omega. .

Abstract

A simple and novel methodology has been developed for the synthesis of 1,3-bis(carboxymethyl)imidazolium chloride [BCMIM][Cl] salt. The ionic salt [BCMIM][Cl] catalyzed the reaction among arylaldehydes; the substituted 1,3-dicarbonyl compounds and urea/thiourea at 80 °C with 5 mol % under neat condition provided the substituted dihydropyrimidin-2(1H)-one/thiones in the synthesis step with yields of up to 96%. In addition, we synthesized the commercially available drug Monastrol by employing this methodology. The new synthesis method employs the benefits of a broad substrate scope, short reaction time, and high atom economy along with low catalyst loading in neat conditions, and is devoid of chromatographic purification. The ionic salt [BCMIM][Cl] was recycled and reused up to six cycles without substantial damage of its catalytic efficiency.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Representative biologically active DHPM compounds.
Scheme 1
Scheme 1. Biginelli Reactions: Previous and Current Approach
Scheme 2
Scheme 2. Synthesis of Ionic Salt 1,3-Bis(carboxymethyl)imidazolium Chloride [BCMIM][Cl]
Figure 2
Figure 2
NMR spectra: (A) 1H NMR spectrum of catalyst 4; (B) 13C NMR spectrum of catalyst 4; and (C) 1H NMR spectrum of compound 8a.
Scheme 3
Scheme 3. Substrate Scope for Various 4-Aryl-3,4-dihydropyrimidin-2(1H)-one/4-Aryl-3,4-dihydropyrimidin-2(1H)- thiones (8a–8a′),
Reaction conditions: The reaction was performed by employing 5 (1.66 mmol), 6 (1.66 mmol), and 7 (1.66 mmol) in one pot at 80 °C in neat condition. Yield of the isolated product.
Scheme 4
Scheme 4. One-Pot Gram-Scale Synthesis of 4-Phenyl-3,4-dihydropyrimidin-2(1H)-ones 8a Employing the [BCMIM][Cl] 4 Catalyst
Figure 3
Figure 3
Plausible iminium mechanism for the synthesis of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones/4-aryl-3,4-dihydropyrimidin-2(1H)-thiones 8a–8a′.
Figure 4
Figure 4
Catalytic cycle (5 mol % of ionic salt at 80 °C in neat condition recharges each reactant in 1.66 mmol).
Scheme 5
Scheme 5. One-Pot Multicomponent Synthesis of Monastrol 8z Using [BCMIM][Cl] 4 Catalyst
See this image and copyright information in PMC

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