Synthesis of Cyanohydrin Acetates
Org. Chem. J. 2010, 1, 1-5
Efficient MgBr2.OEt2 Catalyzed One-Pot Synthesis of
Cyanohydrin Acetates
M. Saeed Abaee,a,* Mohammad M. Mojtahedi,a,* and Hossein Rahimib
a
Chemistry and Chemical Engineering Research Center of Iran, P.O.Box 14335-186, Tehran, Iran
b
Chemistry Department, Islamic Azad University, Saveh Branch, Saveh, Iran
E-mail: abaee@ccerci.ac.ir, mojtahedi@ccerci.ac.ir
Recevied date: February 3, 2010
Abstract
Various cyanohydrin acetates were obtained in good yields by solvent-free treatment of aldehydes with acetic
anhydride and TMSCN in the presence of catalytic amounts of magnesium bromide diethyl etherate.
Keywords: Cyanohydrin acetates, MgBr2.OEt2, aldehydes, TMSCN
1. Introduction
Cyanohydrin esters are considered as important intermediates for the synthesis of many key organic compounds and
exhibit certain biological activities.1-3 In addition, they serve as building blocks for the preparation of more complex
chiral products.4,5 Cyanohydrin esters are traditionally prepared by acylation of cyanohydrin derivatives with acyl
halides or acid anhydrides.6 Additionally, alternative three-component methods are introduced in recent years by
one-pot combination of aldehydes with acyl moieties and a cyanide source. 7-9 Despite these, development of new
methods involving the use of catalytic quantities of a Lewis acid under Solvent-free conditions would still be of
interest.
In recent years, magnesium bromide diethyl etherate (MgBr 2·OEt2) is used as a mild Lewis acid for
convenient manipulation of various organic transformations. 10-12 In this concept, we have shown its applications in
[4+2] cycloadditions,13 Cannizzaro reactions,14 aldol condensation of heterocyclic ketones,15 syntheses of αaminonitrile,16 TMS protection of alcohols,17 Knoevenagel condensation,18 and epoxides nucleophilic ring opening.19
In the present work, we report efficient room temperature combination of various aldehydes, acetic anhydride, and
TMSCN in the presence of 10 mol% MgBr2·OEt2 (Scheme 1).
Scheme 1
1
Abaee et al.
Org. Chem. J. 2010, 1, 1-5
2. Results and Discussion
Initially, solvent-free reaction of benzaldehyde with acetic anhydride and TMSCN was investigated at room
temperature and in the presence of various quantities of MgBr 2.OEt2 as shown in Table 1 (entries 1-4). Experiments
proved that 10 mol% quantities of the catalyst are enough for complete consumption of benzaldehyde within 4
hours. Instead, when ZnBr2 was used (entry 5), formation of no product was detected. Alternatively, LiBr (entry 6)
and AlCl3 (entry 7) gave lower yields of 1a in longer time periods. In a blank experiment (entry 8), no product was
formed indicating the crucial rule of the Lewis acid in the reaction.
Table 1. Optimization of the reaction conditions.
a
Entry
Catalyst
Mol (%)
Time (h)
Yield (%)a
1
MgBr2.OEt2
100
4
64
2
MgBr2.OEt2
50
4
70
3
MgBr2.OEt2
20
4
79
4
MgBr2.OEt2
10
4
86
5
ZnBr2
10
24
<1
6
LiBr
10
16
76
7
AlCl3
100
4
70
8
none
50
4
3
GC yields.
We next used the optimized conditions to synthesize the cyanohydrin acetates of other aldehydes (Table 2).
Consequently, when different aromatic aldehydes bearing electron-withdrawing and electron-releasing groups were
employed (entries 1-4), rapid formation of their respective cyanohydrin products was observed within 4-5 hours. αNaphthaldehyde (entry 5) and heterocyclic aromatic aldehydes (entries 6-7) also reacted conveniently to give high
yields of products 1f-g. Despite aromatic aldehydes, aliphatic substrates reacted sluggishly giving products 1h-i in
moderate yields within 10-12 hours (entries 8-9).
Based on these results, a mechanistic pathway can be suggested through which MgBr 2. OEt2 is
continuously recycled (Scheme 2). This fact that the efficiency of the reactions does not diminish in the presence of
deficient quantities of the catalyst can be attributed to higher Lewis basicity of the starting aldehydes carbonyl
groups in comparison with those of the ester products. This enables the catalyst to detach itself from the cyanohydrin
ester product and be reused in the next cycles.
3. Experimental
Typical Procedure: To a mixture of an aldehyde (2.0 mmol), MgBr2.OEt2 (0.2 mmol, 10 mol%), and TMSCN
(2.4 mmol) was added acetic anhydride (6 mmol). The course of the reaction was monitored by TLC and complete
consumption of the starting aldehyde was noticed within 4-5 hours. At this stage, phosphate buffer (pH=7; 20 mL)
was added to the mixture and the organic content was extracted by diethyl ether (15 mL) and dried over anhydrous
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Synthesis of Cyanohydrin Acetates
Org. Chem. J. 2010, 1, 1-5
Table 2. MgBr2.OEt2 catalyzed cyanohydrin formation reactions.
Entry
Substrate
1
C6H5CHO
86
2
(4-Br)C6H5CHO
86
3
(4-F)C6H5CHO
92
4
(4-Me)C6H5CHO
75
5
α-naphthaldehyde
78
6
2-thienylaldehyde
77
7
2-furylaldehyde
80
8
Me(CH2)2CHO
55
9
acetone
40
a
Product
Yield (%)
Isolated yields.
Na2SO4. The solvent was removed at reduced pressure and the product was purified by column chromatography
(EtOAc/hexane 1:4). All products were characterized by spectroscopic methods and compared with authentic
compounds.4,9,20,21
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Abaee et al.
Org. Chem. J. 2010, 1, 1-5
Scheme 2
4. Conclusion
In summary, an efficient method for one-pot synthesis of cyanohydrin esters of aromatic aldehydes is presented.
Conduction of the reaction at ambient temperature, use of catalytic quantities of MgBr 2.OEt2, and rapid formation of
the products are the advantages of the present procedure.
Acknowledgement
Partial financial support by the Ministry of Science, Research, and Technology of Iran and Islamic Azad University,
Saveh Campus are gratefully appreciated.
References and Notes
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Synthesis of Cyanohydrin Acetates
Org. Chem. J. 2010, 1, 1-5
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