Highly Efficient Michael Addition Reaction of Amines Catalyzed by Silica-Supported Aluminum Chloride

Abstract

Aliphatic and aromatic amines undergo smooth nucleophilic addition to α,β-unsaturated compounds in the presence of a catalytic amount of silica-supported aluminum chloride at 60 °C and under solvent-free conditions to produce the corresponding β-amino compounds in excellent yields. This method is simple and convenient and works efficiently under mild conditions. This catalyst can used again without losing its activity three times.

Keywords:

• Amines
• Michael addition
• silica-supported aluminum chloride
• α,β-unsaturated olefins

INTRODUCTION

Interest in developing environmentally benign and solvent-free reactions has increased dramatically. Consequently, operationally simple catalytic processes, which circumvent the use of toxic materials, have become a powerful tool in constructing an organic transformation.^[ 1-5 ^] One problem for using solvent-free reactions is high catalyst loading, which is generally required to effect the desired transformations in a reasonable time scale.

The Michael reaction is one of the most important carbon–carbon bond-forming reactions. A variety of Michael acceptors, such as α,β-unsaturated ketones, aldehydes, esters, and nitrils, can be used in this reaction, which can be readily transformed into a range of different functionalities.^{[ 6 ]} A large number of methods have been reported quite recently for 1,4-conjugate addition to electron-deficient olefins.

This reaction has been investigated using catalysts such as lanthanum trichloride (LaCl₃),^{[ 6 ]} bromodimethylsulfonium bromide,^{[ 7 ]} silica-supported perchloric acid,^{[ 8 ]} cerium(IV) ammonium nitrate (CAN),^{[ 9 , 10 ]} β-cyclodextrin,^{[ 11 ]} zirconium(IV) chloride,^{[ 12 ]} samarium(III) triflate,^{[ 13 ]} ZrOCl₂ · 8H₂O on montmorillonite K10,^{[ 14 ]} N-methylimidazole,^{[ 15 ]} amberlyst-15,^{[ 16 ]} 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),^{[ 17 ]} bismuth (III) triflate,^{[ 18 ]} cadmium chloride (CdCl₂),^{[ 19 ]} Y(NO₃)₃ · 6H₂O,^{[ 20 ]} and cellulose-supported copper(0).^{[ 21 ]} However, there are various limitations with the reported methodologies, especially when using aromatic amines, such as long reaction times, low yields for aromatic amines, use of halogenated solvents, difficulty in recovery of high-boiling solvents, high temperatures, requirement of special efforts for preparation of the catalysts, use of costly catalysts, and moderate yields.

In the past few years, the use of silica-supported aluminum chloride as a reusable, heterogeneous, inexpensive solid Br⊘nsted acid catalyst has been widely used and received much attention.^[ 22-26 ^] Aluminum chloride is a very active Lewis acid that is soluble in many organic solvents and produces unwanted side reactions. By using silica-supported aluminum chloride, the high reactivity of this active Lewis acid is under control. Silica-supported aluminum chloride is a strong Br⊘nsted and Lewis acid, presumably arising from the formation of SiOAlCl₂ sites on the surface.^{[ 27 ]} This heterogeneous catalyst can be easily separated from the reaction media, has greater selectivity, and is recyclable, easier to handle, more stable, nontoxic, and insoluble in organic solvents.

RESULTS AND DISCUSSION

Because of our interest in studying the Michael reaction under solvent-free and environmentally benign methods,^[ 28-32 ^] herein we report a mild, easy, and catalytic process for Michael addition of aromatic amines at 60 °C and aliphatic amines at room temperature in excellent to quantitative yields using silica-supported aluminum chloride as catalyst. At first, we examined the reaction of aniline with methyl acrylate and 0.2 g of silica-supported aluminum chloride at room temperature under solvent-free conditions. Partial conversion took place within 4 h, leading to Michael adduct. When the temperature was raised to 60 °C, complete conversation took place after 4 h (Scheme 1).^{[ 33 ]} By using 0.1 g of silica-supported aluminum chloride, the reaction was not complete after 4 h at 60 °C. When 0.3 g of catalyst was used, some polymeric materials were also formed as by-products. In the next step, we used piperidine with methyl acrylate and 0.2 g of catalyst at room temperature under solvent-free conditions. After 2 h, the reaction was complete with quantitative yields of the Michael adduct.

Scheme 1 Michael addition of aromatic and aliphatic amines with methyl acrylate.

These results encouraged us to exploit the generality and scope of this reaction by using other Michael acceptors with various aromatic and aliphatic amines under catalytic amounts of silica-supported aluminum chloride. The reaction proceeded well with aromatic and aliphatic amines. As shown in Table 1, by this method, Michael addition of various aliphatic amines and aryl amines carrying either electron-donating or electron-withdrawing substituents were successfully reacted with α,β -unsaturated olefins to produce their corresponding Michael adducts in high to excellent yields. By using this method, Michael addition of 2,4,6-trimethylaniline and imidazole proceeded effectively with α,β -unsaturated compounds, but in low yields of products. Longer reaction times did not improve the yields of the products. The reaction with 4-nitroaniline did not proceed at all, even at higher temperatures. Michael addition with 2-naphthylamine in the presence of 0.2 g of catalyst gave quantitative yield after 20 h at 60 °C.

Table 1. Michael addition of amines catalyzed by silica-supported aluminum chloride under solvent-free conditions

Entry	Amine	Michael acceptor	Product	Time (h)	Yield (%)
1	PhNH2			4.0	Quant.
2				1.5	Quant.
3			N. R
4				4.0	97
5				5.5	85
6				8.0	50
7				2.0	Quant.
8				2.0	Quant.
9				4.0	52
10				2.0	Quant.
11	PhNH2			6.0	75
12				1.5	63
13				6.5	90
14				7.0	60
15				2.0	86
16				5.0	40
17				2.0	72.5
18				10.0	15
19	PhNH2			4.0	Quant. ^a
20				7.0	Quant. ^a, ^b
21				2.0	90
22				5.0	44
23				2.0	77.5
24				8.0	Quant. ^b, ^c
25				20.0	Quant.

Methyl vinyl ketone (MVK) undergoes Michael addition under these reaction conditions. When aromatic amine was used with MVK, a mono-adduct was formed within shorter reaction time (Table 1, entry 19; mixture of 96% of mono- and 4% bis-adducts were formed after 4 h). In the case of 4-chloroaniline and 3,4-dichloroaniline, by using 1.5 equivalent of MVK, less than 10% of bis-adduct was formed after 4 h. When 3 equivalents of MVK was used, bis-adduct was formed with a longer reaction time (Table 1, entries 20 and 24).

We also examined the reaction of aniline with methyl acrylate using different protic and aprotic solvents in the presence of silica-supported aluminum chloride at 50–60 °C. The results showed that solvent-free conditions gave a better yield of β-amino compound (Table 2).

Table 2. Michael addition reaction of methyl acrlylate with aniline in protic and aprotic solvent

Solvent	Yield (%)
C2H5OH	28
H2O	50
ClCH2CH2Cl	89
PhCH3	55
CH3CN	83

Silica-supported aluminum chloride catalyst can be used three times without losing its activity. The recovered silica-supported aluminum chloride was tested in the reaction of aniline and methyl acrylate. The catalyst was still active when it was used for the third time, but the yield of the product decreased each time (Table 3).

Table 3. Activity of the recovered silica-supported aluminum chloride ^a

Run	Yield (%)
1	97
2	69
3	65

A competition reaction was also carried out by using aniline (1 mmol), morpholine (1 mmol), and methyl acrylate (1 mmol) in the presence of silica-supported aluminum chloride at room temperature. After 3 h, compound 6 was formed as major product with small amount of 1 (Scheme 2).

Scheme 2 Competition reaction of aniline and morpholine with methyl acrylate.

The silica-supported aluminum chloride catalyst was prepared according to the reported procedure in the literature.^{[ 6 ]}

CONCLUSION

In conclusion, silica-supported aluminum chloride is among the most efficient catalysts for Michael addition of amines, especially aromatic amines, with different Michael acceptors under solvent-free conditions. This process avoids the use of organic solvent to carry out the reaction, and the catalyst can be separated from the product very easily after the reaction. Handling of the catalyst is easy, and it can be used again.

EXPERIMENTAL

General Procedure for the Synthesis of Compounds 1

Aniline (1 mmol), methyl acrylate (1.5 mmol), and 0.2 g of catalyst were placed into a small flask (or a test tube) and stirred at 60 °C for 4 h. The progress of the reaction was monitored with thin-layer chromatography (TLC). Then ethyl acetate (10 mL) was added, and the solution was filtered. The solid material was washed with 5 mL ethyl acetate, and the combined organic filtrates were dried over Na₂SO₄. The solvent was removed under reduced pressure, and the residue was analyzed by its NMR spectra. In most cases, pure product was obtained. If needed, the residue was separated by silica gel (Merck 80–240 mesh) column chromatography using a 4:1 n-hexane–EtOAc mixture as eluent to afford the pure product. All of the products are known, and the structure of the products were determined from their NMR and IR spectra and by comparison with those reported in the literature.

Selected Spectroscopic Data

Compound 5: ¹H NMR (500 MHz, CDCl₃, CCl₄) δ: 2.20 (s, 9H), 2.64 (t, J = 6.1 Hz, 2H), 3.24 (t, J = 6.1 Hz, 2H), 3.49 (br, 1H), 3.74 (s, 3H), 6.80 (s, 2H).

Compound 6: ¹H NMR (500 MHz, CDCl₃, CCl₄) δ: 2.39 (t, J = 4.4 Hz, 4H), 2.42 (t, J = 7.2 Hz, 2H), 2.60 (t, J = 7.2 Hz, 2H), 3.61 (t, J = 4.4 Hz, 4H), 3.63 (s, 3H).

Compound 10: ¹H NMR (500 MHz, CDCl₃, CCl₄) δ: 2.77 (t, J = 6.6 Hz, 2H), 3.28 (t, J = 6.6 Hz, 2H), 3.60 (br, 1H), 6.90–7.48 (m, 5H).

Compound 12: ¹H NMR (500 MHz, CDCl₃, CCl₄) δ: 2.65 (t, J = 6.1 Hz, 2H), 3.53 (t, J = 6.1 Hz, 2H), 4.00 (br, 1H), 6.55 (d, J = 8.3 Hz, 2H), 7.14 (d, J = 8.3 Hz, 2H).

Compound 19: ¹H NMR (500 MHz, CDCl₃, CCl₄) δ: 2.20 (s, 6H), 2.71 (t, J = 6.8 Hz, 4H), 3.58 (t, J = 6.8 Hz, 4H), 6.60 (d, J = 7.4 Hz, 2H), 7.18 (d, J = 7.4 Hz, 2H).

Notes

^a 96% mono-substitution and 4% bis-substitution products.

^b 100% bis-substitution.

^c Three equivalents of Michael acceptor were used.

^a 1 mmol aniline, 1.5 mmol methy1 acrylate, and 0.2 g silica-supported aluminum chloride were used each time.