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Journal of Green Chemistry and Chemical Engineering
Articles
DOI: 10.55124/jgce.v1i1.19
Submitted: 2021-01-31
Published: 2021-01-31

Natural Products Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology, Habsiguda, Hyderabad 500007, India

ISSN 2831-4158

Synthesis of β-keto-sulfones using alkyl/aryl sulphinates in ionic liquids [bmim-BF4] as an efficient and reusable reaction medium

Authors

  • Suryakiran Navath Natural Products Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology, Habsiguda, Hyderabad 500007, India

Keywords

Alkyl/aryl sulphinates, α-Haloketones, Ionic liquid, bmim-BF4, β-keto-sulfones

Abstract

Synthesis of b-keto-sulfones using alkyl/aryl sulphinates in ionic liquids as en efficient and reusable medium is described. Reaction of α-haloketones with sodium alkyl/aryl sulphinates in ionic liquid afforded the corresponding sulfones in excellent yields. Obtained products were characterized using IR, 1HNMR, 13CNMR and Mass Spectroscopy.

Introduction

-keto-sulfones are of great importance in organic synthesis. The presence of sulfone group, in an organic compound adds variety to its chemical architecture1 and also enhances the biological activity of the compound. The methylene and methyl sulfones are very good -carbanion-stabilizing substituents because strong –IE by the sulfone, but they do not involves conjugation with α-protons. However, the presence of keto group at 3rd position to the sulfone group, adds variety to its functionalities, known as -keto-sulfones, which are very important group of intermediates as they are used in Michael and Knoevenagel reactions,2,3 in the preparation of acetylenes, allenes, chalcones,4-9 vinylsulfones10 and polyfunctionalized 4H-pyrans.11 In addition, they are useful for the synthesis of optically active -hydroxysulfones13 and α-halo methylsulfones.14 This has led to development of novel synthetic methodologies for these compounds. Although several methods of synthesis of ketosulfones have been reported in literature, which includes alkylation of metallic arene sulphinates with either α-haloketone15 or α-tosyloxy ketones,16 acylation of alkyl sulfones,17 reactions of diazo sulfones with aldehydes catalyzed by SnCl2,18 reaction of an acid ester with α-sulfonyl carbanions,19 reaction of an acid anhydride with α-sulfonyl carbanions, addition of aldehydes to α-sulfonyl carbanions followed by oxidation of the resulting -hydroxysulfones,20 oxidation of -ketosulphides,21 oxidation of -ketosulfoxides.22 The direct and straightforward method is the treatment of metallic arene sulphinates with α-haloketone.15 However, the low solubility of metal sulphinate salts in organic solvents is the inadequacy.

In recent years, the use of ionic liquids (ILs) as green solvents in organic synthetic processes has gained considerable importance due to their solvating ability, negligible vapor pressure, easy recyclability and reusability.23 Recently, we have reported the direct synthesis of α-iodo -ketosulfones and their base-induced cleavage to afford α-iodo methyl sulfones.24 In continuation of our work, although not novel, we envisaged the synthesis of ketosulfones using sodium alkyl/aryl sulphinates in bmim-BF4 as a ionic liquid, as efficient and reusable reaction medium

In this report (Scheme 1) we describe an efficient method for the synthesis of sulfones using sodium alkyl/aryl sulphinate in bmim-BF4. This method does not need expensive reagents or special care to exclude the moisture from the reaction medium. We chose bmim-BF4, which are inexpensive and readily available for the preparation of ionic liquid. The resulting salt bmim-BF4 being a liquid at room temperature bmim-BF4. We first examined the reaction of phenacyl bromide 1 with sodium p-toluenesulphinate 2 in bmim-BF4 at room temperature to yield the corresponding sulfone 3 in 98 % yield (Table 2, Entry 1). This result were encouraged us to carry out the reaction in ionic liquids. In order to optimize the reaction conditions, we carried out the reaction in different solvents (Table 1). The poor yields in hydroxylic solvents and less polar solvents are probably due to the lower solubility of the sulphinate salt in these solvents, coupled with the fact that the nucleophile (p-MeC6H4SO2-) is solvated in hydroxylic solvents thereby reducing its effective nucleophilicity. It was observed that bmim-BF4 ability to act as a phase transfer catalyst for this transformation and the reaction was complete very fast (Scheme 2). Reaction of different α-haloketones with alkyl/aryl sulphinates proceeded efficiently and smoothly and the products were obtained in good to excellent yields. Various sulfones have been synthesized in facile manner using ionic liquids as an efficient reaction medium (Scheme 1, Table 2). From the forgoing results, it is evident that the bmim-BF4 is an efficient reaction medium for the synthesis of sulfones. Further, it is noticed that the ionic liquid can be recovered and reused for next run without loss of its activity.

The formation of the product ketosulfones rather than ketosulphinate ester can be explained by soft hard acid base (SHAB) terminology and it follows a reductive dehalogenation followed by neucliophilic attack of sulphinate sulphur in a concerted manner (Scheme 2).

In conclusion we have described synthesis of ketosulfones using sodium sulphinates in bmim-BF4 as an ionic liquid, as efficient and reusable reaction medium. The present procedure for the synthesis of -ketosulfones has the advantage of high efficient reaction medium with high yields of products and simple work-up procedure, which makes it, is a useful and important addition to the present existing methods.

Table 1: Solvent effect on the reaction of phenacyl bromide with sodium p-toluenesulphinate at room temperature
Entry Solvent Time Yield (%)
1 bmim-BF4 5 min 99
2 CH3CN 25 min 95
3 THF 24 h 96
4 1,4 Dioxane 24 h 85
5 EtOH 24 h 50
6 CH3CN 24 h 50
7 IPA 24 h 40
8 C6H6 24 h Nil
9 CHCl3 24 h Nil
10 DCM 24 h Nil

Table 2. Synthesis of β-keto-sulfones using ionic liquid.
Entry Substrate R R1 X R2 Product Time (min) Yielda (%)
1 -Ph H Br p-Toluyl 3a 5 98
2 -Me H Br p-Toluyl 3b 5 98
3 p-Toluyl H Br p-Toluyl 3c 5 95
4 p-Cl(C6H5) H Br p-Toluyl 3d 5 98
5 -Ph H Br -Ph 3e 5 95
6 -Me H Br -Ph 3f 6 98
7 p-Toluyl H Br -Ph 3g 5 98
8 p-Cl(C6H5) H Br -Ph 3h 5 96
9 -Ph H Br -Me 3i 6 96
10 -Me H Br -Me 3j 6 98
11 p-Toluyl H Br -Me 3k 8 98
12 p-Cl(C6H5) H Br -Me 3l 10 98
13 -Ph H Cl p-Toluyl 3m 5 98
14 -Me H Cl p-Toluyl 3n 5 98
15 p-Toluyl H Cl p-Toluyl 3o 5 95
16 p-Cl(C6H5) H Cl p-Toluyl 3p 5 98
17 -Ph H Cl -Ph 3q 5 95
18 -Me H Cl -Ph 3r 6 98
19 p-Toluyl H Cl -Ph 3s 5 98
20 p-Cl(C6H5) H Cl -Ph 3t 5 96
21 -Ph H Cl -Me 3u 10 96
22 -Me H Cl -Me 3v 6 98
23 p-Toluyl H Cl -Me 3w 8 98
24 p-Cl(C6H5) H Cl -Me 3x 10 98
25 -Ph Me Br p-Toluyl 3y 10 98
26 -Ph CN Br p-Toluyl 3z 10 95

aThe reaction was conducted using ionic liquid.

bThe yields are calculated after column purification.

Typical experimental procedure: A mixture of α-haloketone (10 mmol) and sodium alky/aryl sulphinate (11 mmol) in bmim-BF4 (5 mL). The reaction was stirred at RT for an appropriate time (Table 1). After completion of the reaction, as monitored by TLC, the product was extracted into diethyl ether (3 x 20 mL). The combined organic extract was evaporated under reduced pressure to give crude product, which was purified by silica column chromatography. The ionic liquid was recovered and for next run without loss of its activity.

Acknowledgements

The authors are thankful to Director IICT for his constant encouragement and CSIR New Delhi for providing the fellowship.

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2021-01-31

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Navath, S. (2021). Synthesis of β-keto-sulfones using alkyl/aryl sulphinates in ionic liquids [bmim-BF4] as an efficient and reusable reaction medium. Journal of Green Chemistry and Chemical Engineering, 1(1), 8-11. https://doi.org/10.55124/jgce.v1i1.19

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Vol. 1 No. 1 (2022): Journal of Green Chemistry and Chemical Engineering

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Articles