Miceller media accelerated Baylis–Hillman reaction

Abstract

Triton X-100 aqueous micelle accelerates the rate of Baylis–Hillman reaction and enhances the product yield. The type and concentration of surfactants play prominent roles in the reaction. An aqueous micelle Triton X-100 is easily recovered and reused for four runs without substantial loss in yield. 1,4-diazabicyclo[2.2.2]octane (DABCO) (20 mol%) is found to be a good basic catalyst in aqueous micelle. Apparently, this protocol has several advantages such as green reaction medium, mild reaction condition, ease of product recovery and moderate-to-good yield of product.

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Introduction

Since its invention in 1972,¹ the Baylis–Hillman reaction has fascinated chemists owing to its carbon-carbon bond forming ability which offers multifunctional adducts by preserving the atom economy.² The reaction between aldehyde and α-carbon of an electron deficient olefin in the presence of tertiary amine furnishes a multifunctional product which has extensive uses in a myriad of synthetic contexts.³ However, the main shortcomings of this reaction include slow reaction rate, moderate yield and inertness to enones, α,β-substituted aldehydes and hindered aldehydes. The need of improvement in reaction rate, product yield and environmental benign nature was met by using water as reaction medium.⁴ Hitherto, the reaction is being practised by various methods involving different strategies viz. ionic liquids,⁵ PEG-400,⁶ sulpholane,⁷ supercritical CO₂,⁸ ultrasound,⁹ high pressure,¹⁰ microwave irradiation,¹¹ aqueous acidic media,¹²etc. Literature data reveal that generally in a Baylis–Hillman reaction, polar solvents are employed as they increase the equilibrium constant of the zwitterionic intermediate, formed during the course of the reaction.^13,14 Indeed, low solubility of reactant and incompatibility of intermediate hamper the reaction rate in aqueous medium. This problem could be encountered with use of miceller media, a microheterogenous system. In recent years aqueous micelles are widely used for chemical reactions.^15,16

Herein, we present our observations about the potential use of miceller solution, TX 100 surfactant in aqueous medium, for a Baylis–Hillman reaction in presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) at room temperature (Scheme 1). It is intriguing to note that the presence of water insoluble reactants within the hydrophobic core of miceller media boost the rate of reaction.

Scheme 1 Baylis–Hillman reaction in TX-100 aqueous micelles.

Results and discussion

With regards to optimization of the reaction conditions, the reaction between 2-nitrobenzaldehyde and acrylonitrile was selected as a model reaction. Initially, when this reaction was carried out in the presence of water alone, the reaction was found to be very sluggish, because of poor solubility of aldehydes in water (entry 1, Table 1). Also, in the presence of organic solvent such as THF and dioxan, negligible improvements in the results were observed even though reactions were carried out for a longer period (entries 2, 3, Table 1). Moreover, cationic surfactant cetyl trimethylammonium bromide (CTAB) and anionic surfactant sodium dodecyl sulfate (SDS) offered good conversion and yield at 10 wt% concentration (entries 4, 5, Table 1). Although the ionic surfactants offered good results, the toxicity and cost of these surfactants limited their use. Hence we decided to use non-ionic surfactant TX-100 aqueous micelles. To our delight the best result was obtained with TX-100 aqueous micelles.

Table 1 Influence of different systems on the Baylis–Hillman reaction^a

Entry	Solvents	Time/h	Conversion (%)^b	Yield^c
a Reagents and reaction conditions: 2-nitrobenzaldehyde (1 mmol) and acrylonitrile (2 mmol); TX-100 aqueous micelles (10 wt%), DABCO (20 mol%), room temperature. b % conversion was monitored by gas chromatography. c Isolated yield.
1	Pure water	12	55	52
2	THF	48	58	56
3	1,4-dioxan	48	62	60
4	10 wt% CTAB/H2O	2	86	78
5	10 wt% SDS/H2O	2	82	76
6	5 wt% TX-100/H2O	2	90	88
7	10 wt% TX-100/H2O	1	92	90
8	20 wt% TX-100/H2O	1	85	78
9	50 wt% TX-100/H2O	1	84	78

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Concurrently, we found that the concentrations of TX-100 aqueous micelle influenced the rate of conversion and yield of product. The reaction conversion increased with increase in concentration of TX-100 owing to enlargement of the interfacial area and lower mass transfer resistance¹⁵ (entries 6, 7, Table 1). The best conversion of 92% was obtained in 10 wt% TX-100 aqueous micelles. However, further increase in concentration inversely affected the conversion rate (entries 8, 9, Table 1). This was mainly for unused excess TX-100 surfactant, which formed a mask around its own micelle, and hence inhibited the interaction between the substrates.

The catalytic effect of TX-100 micelles in the Baylis–Hillman reaction is illustrated in Fig. 1. In the presence of TX-100 aqueous micelles, the water insoluble substrates migrated into the hydrophobic core of micelle. The enhancements in the reactivity of aldehydes and activated olefins are more in aqueous micellar solution than in pure water and/or different organic solvents. This may be due to the micelles' ability to work as micro- or nanoreactor¹⁷ and to stabilize the zwitterionic intermediate, generated from the Michael addition of Lewis base to the activated olefins. The presence of zwitterionic intermediate and aldehyde in the pseudo phase region of micellar solution accelerates the nucleophilic addition, thus offering the Baylis–Hillman adducts in good-to-excellent yield.

Fig. 1 Tentative mechanism of the Baylis–Hillman reaction in micelles.

All the aforementioned results revealed that DABCO in 10 wt% TX-100 aqueous micelles is the best choice for Baylis–Hillman reaction. To explore generality and scope of the protocol, we treated various substituted aldehydes with acrylonitrile/ethyl acrylate (Table 2). The conversion gave the product in good-to-excellent yield under notably practical conditions. The physical and spectral data of all the compounds are in good agreement with the literature.^4–12

Table 2 DABCO-catalyzed Baylis–Hillman reaction in 10 wt% TX-100 aqueous micelles^a

Entry	Aldehyde	Activated olefin	Time/h	Yield^b (%)
a Reagents and reaction conditions: aldehyde (1 mmol) and acrylonitrile or ethyl acrylate (2 mmol); TX-100 aqueous micelles (10 wt%), DABCO (20 mol%), room temperature. b Isolated yield.
1			2	92
2			1.5	94
3			1.5	95
4			1.5	90
5			2.5	85
6			5.0	72
7			2	90
8			1.5	87
9			1.5	92
10			2.0	87
11			2.5	82
12			3.0	88
13			4.0	75
14			4.5	80
15			4.5	64

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The investigation of recyclability of reaction media revealed that the reaction media could be recycled and reused for four consecutive cycles offering the same conversions and negligible loss in yield (Table 3). Upon completion of the reaction the product and unutilized starting materials were extracted using diethyl ether and thus separated micellar media were reused for the next cycle.

Table 3 Recyclability of TX-100 micellar media^a

Runs	Conversion (%)^b	Yield^c
a Reagents and reaction conditions: 2-Nitrobenzaldehyde (1 mmol) and acrylonitrile (2 mmol); TX-100 aqueous micelles (10 wt%), DABCO (20 mol%), room temperature. b % conversion was monitored by gas chromatography. c Isolated yield.
1	92	90
2	92	88
3	91	87
4	92	83

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Conclusion

In summary, micellar media accelerated inventive synthetic protocol has been successfully established for the Baylis–Hillman reaction. The reaction is catalyzed by 10 mol% DABCO in micellar media. The process has several advantages over the many documented procedures from economical and environmental points of view, such as operational simplicity, short reaction time, excellence in yield and recyclability of the reaction media. We believe that this will provide a better and more practical alternative to the existing methodologies for large scale production.

Experimental

All commercial reagents and solvents were procured from s. d. fine chemicals (India) and were used without further purification. However, 1,4-diazabicyclo[2.2.2]octane (DABCO) was purchased from Ms. Spectrochem Ltd., Mumbai. The reaction was monitored by TLC using 0.25 mm E-Merck silica gel 60 F₂₅₄ precoated plates, which were visualized with UV light. Analysis was performed on gas chromatograph (chemito 8610) with flame ionization detector. A 4 m long i.d. S.S. column packed with OV-17 on chromosorb WHP was employed for the analysis. Nitrogen was used as carrier gas at a flow rate of 30 mL m⁻¹. Infrared spectra were recorded on a Perkin-Elmer spectrum 100 FT-IR spectrometer. ¹H NMR spectra were recorded on Bruker Avance 400 MHz spectrometer in CDCl₃, using TMS as an internal standard.

General procedure for Baylis–Hillman in TX-100 aqueous micelles

Into a stirred solution of aldehyde (1 mmol) and acrylonitrile/ethyl acrylate (2 mmol) in 10 wt% TX-100 aqueous micelles (5 mL) was added DABCO (20 mol%) and the vigorous stirring was continued at room temperature. The progress of the reaction was monitored by TLC. After completion of reaction, as indicated by TLC and GC, the product was extracted with diethyl ether (3 × 10 mL). The collective organic phase was dried and concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography.

Representative spectral data

3-Hydroxy-2-methylene-3-(2-nitrophenyl) propane nitrile (Entry 2). ¹H NMR (400MHz, TMS, CDCl₃) δ: 7.99–8.02 (d, 1H, J = 7.0 Hz, Ar–H); 7.84–7.87 (d, 1H, J = 7.0, 1.5 Hz, Ar–H), 7.70–7.72 (dd, 1H, J = 6.6, 1.2 Hz, Ar–H), 7.50–7.55 (dd, 1H, J = 6.6, 1.2 Hz, Ar–H), 6.08 (s, 2H, olefinic H), 6.00 (s, 1H, CH), 3.94 (s, 1H exchangeable, −OH).

FT IR (cm⁻¹): 3434, 2861, 2228, 1608, 1524, 1347, 1185, 859, 789, 731.

Mass (m/z): theoretical 204, observed 204, (M − 1) 203.

Acknowledgements

The authors are greatly thankful to RSIC, I.I.T Mumbai for providing the ¹H NMR and mass spectroscopy facilities, and Dr S.T. Gadade for his benevolent support.

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