NOTE pubs.acs.org/joc
An Effective Method To Prepare Imines from Aldehyde, Bromide/Epoxide, and Aqueous Ammonia Jing-Mei Huang,*,† Jue-Fei Zhang,† Yi Dong,† and Wen Gong‡ †
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, People’s Republic of China ‡ Blue Star Xinghuo Silicone Plant, Jiujiang 330319, People’s Republic of China
bS Supporting Information ABSTRACT: A three-component reaction of aldehydes, alkyl bromides, and ammonia to form imines was studied. Aqueous ammonia was applied as the nitrogen source and solvent in the reaction. For the aromatic aldehyde, the product yields are good to excellent and the reaction conditions are mild to be compatible with a range of functional groups. The reaction of aldehydes and aqueous ammonia with epoxides was also studied and imines bearing a vicinal hydroxyl group can be obtained efficiently and regioselectively. And studies showed that this method allows the synthesis of primary amines and especially 1,2-amino alcohol selectively in high yield. It is proposed that the reaction pathway might involve a key intermediate of hydrobenzamide.
I
mines are widely used in the synthesis of natural products, nonnatural amino acids, pharmaceutical and medicinal compounds such as β-lactam, as well as polymers and materials.1 Imines are often obtained by the condensation of amines with the carbonyl compounds,2 and they can also be obtained by the oxidative condensation of amines,3 oxidation of amines,4 and the oxidative coupling of alcohols and amines.57 For the method of condensation of amines with the carbonyl compounds, although it is a well-established, direct, and attractive synthetic route to prepare imines, problems still remain to achieve this chemical transformation economically. For many years, azeotropic distillation was the most popular technique to remove the liberated water. Molecular sieves, dehydrating solvents, or Lewis acid catalysts have been shown to remove water as well as facilitate nucleophilic attack on the carbonyl compound. These methodologies suffer from high reaction temperatures, prolonged reaction times, high cost, or moisture sensitive reagents/catalysts. Given the importance of imines as intermediates in organic synthesis, the development of convenient procedures for their preparation is of interest. In recent years, aqueous protocols have received considerable attention and developed very fast.8 In connection with our interests in aqueous medium reactions,9 herein we disclose a novel three-component tandem reaction to prepare imines from aldehydes, bromides/epoxides, and aqueous ammonia under mild conditions. The reaction of benzaldehyde and 1-bromobutane was initially investigated in 3.0 M aqueous ammonia at room temperature. However, there was no imine observed. When the reaction was carried out at 60 °C, a 40% yield of desired imine was obtained (entry 2, Table 1). Increase of the concentration of ammonia r 2011 American Chemical Society
Table 1. Optimization of the Reaction Conditions for the Three-Component Tandem Reaction to Prepare Imine 3aa
solution
temp (°C)
yield (%)b
entry
X
1
Br
3 M aq ammonia
rt
0
2
Br
3 M aq ammonia
60
40
3
Br
9 M aq ammonia
60
80
4
Br
28% (w/w) aq ammonia
60
91
5 6
Br Br
28% (w/w) aq ammonia 28% (w/w) aq ammonia
45 75
65 82
7
I
28% (w/w) aq ammonia
60
90
8
Cl
28% (w/w) aq ammonia
60
22
a
Reaction conducted with benzaldehyde (0.5 mmol), 2a (0.75 mmol) in aqueous ammonia (1 mL), overnight. b Isolated yields.
resulted in an increase of the yield (entries 3 and 4, Table 1). Optimization on the concentration of ammonia showed that the yield reached 91% in 28% (w/w) aqueous ammonia (entry 4, Table 1). When the reaction was carried out at higher temperature (75 °C), the desired imine was isolated with a small decrease of yield (entry 6, Table 1). For 1-iodobutane and 1-chlorobutane, Received: December 11, 2010 Published: March 23, 2011 3511
dx.doi.org/10.1021/jo102455q | J. Org. Chem. 2011, 76, 3511–3514
The Journal of Organic Chemistry
NOTE
Table 2. Formation of Imines from Aldehydes and Bromides in Aqueous Ammoniaa
R1
entry
R2
yield (%)b
product
1
Ph
n-Bu
3a
2
Ph
i-Pr
3b
86
3
Ph
PhCH2
3c
91
4
Ph
CH2dCHCH2
3d
90
5 6
Ph Ph
CH3CHdCHCH2 CNCH2CH2
3e 3f
85 90
7
4-Cl-C6H4
n-Bu
3g
89
8
4-CN-C6H4
n-Bu
3h
78c
9
2-thienyl
n-Bu
3i
82
2-HO-C6H4
n-Bu
3j
85
10
Scheme 1. Studies on the Reaction of Preform 6 with Bromide
91
11
2-Br-C6H4
CH2dCHCH2
3k
94
12
4-Cl-C6H4
CH2dCHCH2
3l
92
13 14
2-furyl 4-O2N-C6H4
CH2dCHCH2 CH2dCHCH2
3m 3n
93 92c
15
PhCHdCH
CH2dCHCH2
3o
89
16
n-Pr
n-Bu
3p
10d
17
n-Pr
PhCH2
3q
32d
18
n-Pr
CH2dCHCH2
3r
