A Facile Solvent Free Claisen-Schmidt Reaction: Synthesis of α,α′-bis-(Substituted-benzylidene)cycloalkanones and α,α′-bis-(Substituted-alkylidene)cycloalkanones

A F M Motiur Rahman,Roushown Ali,Adnan A Kadi,Yurngdong Jahng

doi:10.3390/molecules17010571

A F M Motiur Rahman, Roushown Ali + Show 2 more

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https://doi.org/10.3390/molecules17010571

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Abstract

Solvent-free Claisen-Schmidt reactions of cycloalkanones with various substituted benzaldehydes (aryl aldehydes) using solid NaOH (20 mol%) and applying a grinding technique were studied. Quantitative yields (96–98%) of α,α'-bis-(substituted-benzylidene)cycloalkanones were obtained. Aliphatic aldehydes also provided α,α'-bis-(substituted-alkylidene)cycloalkanones in very good yields with minor amounts of α-(substituted-alkylidene)cycloalkanones. The catalytic performance of solid NaOH was examined. The molar ratio of NaOH was optimized. The catalytic effect of solid NaOH was also evaluated by comparing it with KOH, NaOAc, and NH4OAc and it turns out that 20 mol% of solid NaOH was good enough to catalyze the Claisen-Schmidt reactions of cycloalkanones with various substituted benzaldehydes. Additionally, the regioselectivity of the Claisen-Schmidt reaction of acetone with benzaldehyde was examined. Using the same method, we could synthesize the corresponding bis-benzylidene- and mono-benzylideneacetone separately in 98% and 96% yields, respectively.

Highlights

The Claisen-Schmidt reaction is a condensation reaction of aldehydes and carbonyl compounds leading to -hydroxycarbonyl compounds and it has played an important role in synthetic organic chemistry [1,2,3,4,5,6]
Comparing all the results with our previously reported methods [74,75], we found that mol% of solid NaOH and grinding with a mortar and pestle for 5 minutes is better than any other catalyst for the Claisen-Schmidt reaction of cyclohexanone (1b) with benzaldehyde (2a)
A facile solvent-free Claisen-Schmidt reaction between cyclopentanone (1a)/cyclohexanonoe (1b) and different substituted benzaldehydes 2a–h catalyzed by solid NaOH (20 mol%) by applying a grinding technique using a mortar and pestle for 5 minutes was performed, resulting in excellent yields

Summary

Introduction

The Claisen-Schmidt reaction (crossed-aldol reaction) is a condensation reaction of aldehydes and carbonyl compounds leading to -hydroxycarbonyl compounds and it has played an important role in synthetic organic chemistry [1,2,3,4,5,6]. Subsequent dehydration of the β-hydroxycarbonyl compounds afford α-alkylidene or α-arylidene compounds. Studies on the Claisen-Schmidt reaction have been focused on -alkylidene- and -arylidene-carbonyl compounds, interest in , -bisalkylideneand , -bisarylidene-carbonyl compounds is increasing. -bis-(substitutedbenzylidene)-cycloalkanones have been attracting much more attention, due to their intriguing biological activities such as antiangiogenic [7,8], quinine reductase inducer [9], arginine methyltransferase inhibitor [10], cytotoxicity [11,12], cholesterol-lowering activity [13], uses in agrochemicals, pharmaceuticals and perfumes [14], in bis-spiropyrrolidines [14,15,16], and as liquid crystalline polymer units [17], and as important precursors for the synthesis of pyrimidine derivatives [18], 2,7-disubstituted tropones [19], and they are the synthetic intermediates of choice to functionalize the , β-position during the total synthesis of natural products such as the cystodytins [20]. The Claisen-Schmidt reactions of cycloalkanones leading to , -bis-(benzylidene)cycloalkanones are classically catalyzed by strong acids [23,24] and more likely by base with or without solvent [25,26,27,28,29,30,31,32,33,34,35]

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