Journal of Chemistry

Volume 2013 (2013), Article ID 989285, 5 pages

http://dx.doi.org/10.1155/2013/989285

Research Article

Catalyst-Free and Highly Selective N,N-Diallylation of Anilines in Aqueous Phase

Zhengyin Du, Xiaohong Wei, Wenwen Zhang, Yuanmin Zhang, and Qunji Xue

Key Laboratory of Eco-Environment-Related Polymer Materials of Ministry of Education, Key Laboratory of Polymer Materials of Gansu Province, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China

Received 4 June 2012; Revised 15 July 2012; Accepted 23 July 2012

Academic Editor: Ana Moldes

Copyright © 2013 Zhengyin Du et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

A highly selective diallylation reaction of anilines with allyl bromide was achieved in aqueous alcohol solution in the presence of potassium carbonate and without the use of any catalyst. The reaction tolerates a wide range of functionalities, and various tertiary amines were obtained in the yield of up to 99% with complete conversion of anilines.

1. Introduction

N-alkylation of aniline derivatives is an important reaction in organic synthesis, which has been widely applied in the preparation of dyes, fluorescence probes, agrochemicals, and pharmaceuticals [1]. The challenge of this reaction is to obtain excellent selectivity for mono- or dialkylation products and to avoid the formation of corresponding quaternary ammonium salts from N,N-dialkylaryl amines. Many methods have been reviewed for the synthesis of substituted amines [2, 3]. However, they are still suffering some problems, such as the use of toxic reagents [4] and the control of the selectivity of mono- and dialkylation-aniline derivatives [5]. In order to overcome these problems, noble metal complexes and salts involving Ru [6], Ir [7, 8], Pt [9], Au [10, 11], and Pd [12, 13] as catalysts and alcohols as alkylating agents have been reported extensively in homogeneous phase. Transition metal-free protocols have also been described, although they normally require harsh reaction conditions, such as high temperatures and pressures, to achieve reasonable yields of products [14]. Compared to homogeneous catalysts, heterogeneously catalysed methodologies based on Ra-Ni [15] and magnetite [16] have been proposed as alternatives to prepare monoalkylation products. Recently, microwave irradiation has been proved to be efficient for the syntheses of N-alkyl anilines [17]. However, they all suffered from high temperatures and long reaction times. Moreover, the dialkylation products were not involved or were only byproducts in the previously mentioned literatures.

In recent years, Ju and Varma [18, 19] disclosed direct generation of tertiary amines by N-alkylation reaction of amines with alkyl halides in aqueous phase under microwave irradiation. But the alkylations focused mainly on the reactions of secondary amines with alkyl halides and primary amines with dihaloalkanes. The ionic liquid BMImPF₆ and silica were also reported to improve the N,N-bisallylation of amines with allyl bromide [20, 21]. But the conversion of most of substrates is very low, the selectivity of diallylation products is poor, and the needed reaction time is long. Besides, few of literatures were reported for bisallylation reaction of anilines. Therefore, it is necessary to make great efforts on the preparation of N,N-diallylanilines derivatives by one-step diallylation of anilines.

As a basis of this investigation, we report herein one-step diallylation of anilines by allyl bromide in mildly basic aqueous media to afford a series of N,N-diallylanilines in a simple and straightforward manner (Scheme 1).

Scheme 1: One-step diallylation of anilines.

2. Experimental

A mixture of aniline (0.5 mmol), allyl bromide (1.5 mmol), potassium carbonate (2 mmol), ethanol (2 mL), and water (1 mL) was added to a 50 mL round flask and stirred at 70°C for the desired time until complete consumption of starting material as judged by TLC. Then, the reaction mixture was condensed by evaporation of solvents under reduced pressure and was washed with saturated sodium carbonate solution and poured into a separating funnel. The content was extracted with ethyl acetate (10 mL × 3), and the combined organic layers were dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure to afford the crude products, which were further purified by column chromatography on silica gel using petroleum ether and ethyl acetate as the eluents.

Physical spectroscopic data of new product: N-allyl-4-chloro-2-nitrobenzenamine (3p): yellowish crystal; Mp: 49-50°C; ¹H NMR (400 MHz, CDCl₃, ppm) δ 3.93 (s, 2H, CH₂), 4.76 (s, 1H), 5.24–5.34 (m, 2H, =CH₂), 5.90–5.99 (m, 1H, CH), 6.38 (d, J = 8.0 Hz, 1H, NH), 7.44–7.50 (m, 2H, Ar-H); ¹³C NMR (100 MHz, CDCl₃, ppm) δ 147.8, 144.3, 133.2, 129.3, 125.2, 117.31, 111.8, 105.5 (all unsaturated CH), 45.8 (CH₂); MS (EI) m/z (%): 212, 185, 177 (100), 165, 139, 131, 77; IR (KBr, υ/cm⁻¹): 3394 (NH), 1616 (C=C), 1532, 1344 (C–N), 805, 734; Anal. calcd for C₉H₉ClN₂O2 (212.04): C, 50.84; H, 4.27; found: C, 50.72; H, 4.10.

3. Results and Discussion

To begin our study, a standard reaction between aromatic amines and allyl bromide was carried out under different reaction conditions. The reaction of commercial available and inexpensive aniline (1a) with allyl bromide was chosen as a model under catalyst-free conditions. The reaction progress was detected by TLC until aniline disappeared completely (Table 1). When aniline reacted with excess of allyl bromide in the absence of any base in ethanol at 70°C, the desired product N,N-diallylaniline (2a) was obtained only in 14% of yield, whereas N-allylaniline (3a) was a major product with the yield of 32% (Table 1, entry 1). Subsequently, various bases were investigated for this reaction. Poor selectivity and low yield of 2a were observed in the presence of Na₂CO₃ and NaHCO₃ (Table 1, entries 2 and 3). However, the good yield of 86% was achieved, and only trace of 3a was observed when using K₂CO₃ as a base (Table 1, entry 4). The amount of potassium carbonate was further examined and found that 4 equivalents were beneficial to the aimed product (Table 1, entries 4–6). The exploration of this reaction at different temperature revealed that the yield and the selectivity of 2a increased simultaneously with the temperature increase (Table 1, entries 4, 7, and 8). Considering the solubility of K₂CO₃ in ethanol is very low, the mixture of ethanol and water was used as reaction medium. It is found that water can affect the alkylation manifestly (Table 1, entries 4 and 9–12). The presence of a small quantity of water in the reaction system is in favour of shortening reaction times and improving the yield and selectivity of 2a. A brief optimization reveals that a mixture of ethanol and water (2/1 mL) is the most suitable medium for the desired transformation, in which aniline can be completely converted to the dialkylation product with the yield of 86% in 2 hours (Table 1, entry 9).

Table 1: Optimization of the reaction conditions of aniline with allyl bromidea.

Entry
Base (mmol)
Temp (°C)
Solvent (mL)
Time (h)
Yield (%)b

2a [22]
3a [22]

1
None
70
C₂H₅OH (3)
5.5
14
32

2
Na₂CO₃ (2)
70
C₂H₅OH (3)
5.5
54
16

3
NaHCO₃ (2)
70
C₂H₅OH (3)
5.5
59
Trace

4
K₂CO₃ (2)
70
C₂H₅OH (3)
5.5
86
Trace

5
K₂CO₃ (1.5)
70
C₂H₅OH (3)
5.5
65
8

6
K₂CO₃ (2.5)
70
C₂H₅OH (3)
5.5
74
Trace

7
K₂CO₃ (2)
RT
C₂H₅OH (3)
7
35
35

8
K₂CO₃ (2)
40
C₂H₅OH (3)
6.5
68
31

9
K₂CO₃ (2)
70
C₂H₅OH/H₂O (2/1)
2
86
Trace

10
K₂CO₃ (2)
70
C₂H₅OH/H₂O (1/1)
2
49
19

11
K₂CO₃ (2)
70
C₂H₅OH/H₂O (1/2)
2
57
4

12
K₂CO₃ (2)
70
H₂O (3)
2
30
23

aReaction conditions: aniline (0.5 mmol), allyl bromide (1.5 mmol), and TLC detection.

bIsolated yield by column chromatography. The products are known and characterised thoroughly by NMR, IR, MS, and elemental analysis, which were consistent with literature data.

The molar ratio of aniline and allyl bromide was also optimized. As seen in Table 2, the ratio affected the reaction significantly. The best yield of N,N-diallylaniline was obtained when 3 equivalents of allyl bromide relative to aniline were used (Table 2, entry 3).

Table 2: Effect of the amount of allyl bromide on the reactiona.

Entry
1a/allyl bromide (mmol)
2a (%)b
3a (%)b

1
1 : 2
27
26

2
1 : 2.4
50
30

3
1 : 3
86
Trace

4
1 : 3.6
86
Trace

aReaction conditions: aniline (0.5 mmol), K₂CO₃ (2 mmol), C₂H₅OH (2 mL), H₂O (1 mL), 70°C, 2 hours.

bIsolated yield.

In this regard, the direct diallylation reactions of various substituted anilines were explored under the above optimized conditions, and the results are listed in Table 3. From this Table, it can be seen that the electronic and steric hindrance effects of substituents affect the reaction time and the yield of aimed product significantly. Anilines with electron-donating substituents, such as methoxy and methyl, were smoothly converted to the corresponding diallylation products in good-to-excellent yield with excellent selectivity (Table 3, entries 1–8). Halogen atom(s) attached on the aromatic ring decreased the yield and selectivity of 2, as a little of 3 was observed as byproduct (Table 3, entries 9–11). For 2,5-dichloroaniline, trace of the diallylation product was detected, whereas the monoalkylation product was obtained in 74% of yield (Table 3, entry 12), which might be due to the large steric hindrance of the substrate. The electron-withdrawing substituents, such as nitrogroup, reduced the electron cloud density of nitrogen on amino group, thus reducing the nucleophilicity of anilines. As a result, the diallylation almost could not occur, and only about 40% of monoallylation products were gained for ortho- and paranitroaniline (Table 3, entries 14–16). It is unexpected that 3-nitroaniline gave 80% of N,N-diallylaniline as well as 15% of N-allylaniline (Table 3, entry 13). This may be the cause of none of hindrance and small effect on the nucleophilicity of amino group. 2,4-Dichloro-6-nitroaniline did not react with allyl bromide under the same conditions (Table 3, entry 17). Obviously, it is the result of synergetic effect of steric hindrance and electronic effect of substituents.

Table 3: Synthesis of N,N-diallylanilines from various anilines and allyl bromidea.

Entry
of Anilines
Time (h)
Yield (%)b

1
1a
H
2
2a [22], 86
Trace

2
1b
2-CH₃
4
2b [23], 68
Trace

3
1c
3-CH₃
1
2c [24], 96
—c

4
1d
4-CH₃
1.5
2d [23], 98
—c

5
1e
2,4-(CH₃)₂
2
2e [23], 92
Trace

6
1f
2-CH₃O
1.5
2f [23], 91
—c

7
1g
4-CH₃O
1
2g [23], 99
—c

8
1h
2,5-(CH₃O)₂
2
2h [25], 93
Trace

9
1i
3-Cl
3.5
2i [25], 76
3i [25], 23

10
1j
4-Cl
3.5
2j [22], 77
3j [22], 10

11
1k
4-Br
3.5
2k [20], 78
3k [20], 20

12
1l
2,5-Cl₂
6
Trace
3l [26], 74

13
1m
3-NO₂
5
2m [26], 80
3m [27], 15

14
1n
4-NO₂
6
Trace
3n [22], 42

15
1o
2-NO₂
6
Trace
3o [28], 38

16
1p
4-Cl-2-NO₂
24
Trace
3p, 37

17
1q
2,4-Cl₂-6-NO₂
24
NR

aReaction conditions: anilines (0.5 mmol), allyl bromide (1.5 mmol), K₂CO₃ (2 mmol), C₂H₅OH (2 mL), H₂O (1 mL), 70°C, TLC detection.

bIsolated yield; all known products are characterised thoroughly by NMR, IR, MS, and elemental analysis, which were consistent with literature data.

cNot observed.

4. Conclusions

In conclusion, we have developed a direct, green, and highly efficient method for the synthesis of N,N-diallylaniline in aqueous phase under mild conditions. The advantages of this protocol include avoiding the use of any catalyst and toxic organic solvents, complete conversion of anilines, high-to-excellent yield and selectivity, short reaction times, and avoiding the overalkylation to form quaternary ammonium salts.

Acknowledgments

The authors gratefully acknowledge National Natural Science Foundation of China (20702042), Program for Changjiang Scholars and Innovative Research Team in University (IRT1177), Key Laboratory of Polymer Materials of Gansu Province (zd-06-18), and NWNU Young Teachers Research Improving Program (NWNU-LKQN-10-11) for financial support.

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