An efficient method for synthesis of phenacyl derivatives under homogeneous phase transfer catalyst condition in aqueous media

Article abstract of DOI:10.1016/j.cclet.2010.10.009

In this letter, a mild and efficient procedure for synthesis of phenacyl derivatives under homogenous catalysis in the presence of tetrabutylammonium bromide in aqueous media is described. The nucleophilic substitution reactions were performed under ecofriendly conditions and gave the corresponding products in high yields and short reaction times.

Full text of DOI:10.1016/j.cclet.2010.10.009

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 300–302
www.elsevier.com/locate/cclet
An efficient method for synthesis of phenacyl derivatives under
homogeneous phase transfer catalyst condition in aqueous media
b
Soheil Sayyahi a, , Jafar Saghanezhad
*
a Chemistry Department, Islamic Azad University, Mahshahr Branch, Mahshahr 63519, Iran
b Chemistry Department, College of Science, Shahid Chamran University, Ahvaz 61357-4-3169, Iran
Received 28 June 2010
Available online 22 December 2010
Abstract
In this letter, a mild and efficient procedure for synthesis of phenacyl derivatives under homogenous catalysis in the presence of
tetrabutylammonium bromide in aqueous media is described. The nucleophilic substitution reactions were performed under
ecofriendly conditions and gave the corresponding products in high yields and short reaction times.
# 2010 Soheil Sayyahi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Tetrabutylammonium bromide; Nucleophilic substitution; Synthesis of phenacyl derivatives
The phenacyl compounds are useful intermediates in organic synthesis and have attracted a great deal of interest
[1,2]. Derivatives of a-keto compounds were opened an important area of heterocyclic chemistry on account of the
fact that many of them are subunits of natural products and pharmaceutical agents. Azide and thiocyanate derivatives
of a-keto compounds are useful intermediates in the synthesis of heterocyclic compounds such as pyrroles, oxazoles
and thiazoles [3–5]. Due to their instability, a-iodo ketones have been scarcely used, except in some reactions like the
Rap– Stoermer that has been reported for the synthesis of benzofurans [6]. Unfortunately, the few synthetic methods
that available for synthesis of azide, thiocyanate, cyanide and iodide derivatives of a-keto compounds are tedious and
need some complex and environmentally high-impact reagents [7].Recently, because of the cost, availability, and
compatibility across phases in biphasic organic-aqueous layer heterogeneous reaction systems with water as solvent,
tetrabutylammonium bromide (TBAB) plays an important role as a homogeneous catalyst in various organic
transformations [8–15]. On the basis of these drawbacks and in continuation of our ongoing effort to introduce novel
catalysts for organic transformation [16,17], we decided to investigate the application of TBAB as a catalyst for
synthesis of a-keto derivatives in water.
1. Experimental
All of the phenacyl derivatives were prepared by our procedure; their spectroscopic and physical data were
compared with those of authentic samples. NMR spectra were recorded in CDCl3 on a Bruker Advanced DPX
* Corresponding author.
E-mail address: sayyahi.soheil@gmail.com (S. Sayyahi).
1001-8417/$ – see front matter # 2010 Soheil Sayyahi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.10.009

S. Sayyahi, J. Saghanezhad / Chinese Chemical Letters 22 (2011) 300–302
301
Table 1
Results of the treatment of a-bromo acetophenone derivatives with various nucleophiles.
[TD$INLE]
O
O
Br
X
TBAB (0.25 mmol)/ Water
.
KX (2 mmol), mix, r.t
X: SCN, N3, I, CN
R
R
1 mmol)
Yield: 95-40%
Entry
a-Bromo acetophenone derivatives
X
Time (min)
Yielda,b (%)
O
1a
1b
1c
1d
N3
SCN
I
30
40
40
70
87
92
90
45c
Br
[TD$INLINE]
CN
H
O
2a
2b
2c
2d
N3
SCN
I
30
25
30
90
94
95
92
40c
Br
[TD$INLINE]
MeO
CN
O
3a
3b
3c
3d
N3
SCN
I
15
30
90
93
91
65c
Br
[TD$INLINE]
30
CN
110
O2N
O
4a
4b
4c
4d
N3
SCN
I
25
35
30
45
92
93
90
40c
Br
[TD$INLINE]
CN
Br
a
Products were identified by comparison of their physical and spectral data with those of authentic samples
b
c
Isolated yields.
The results according to GC analysis.
400 MHz instrument spectrometer using TMS as internal standard. IR spectra were recorded on a BOMEM MB-Series
1998 FT-IR spectrometer. The purity determination of the products and reaction monitoring were accomplished by
TLC on silica gel polygram SILG/UV 254 plates.
To a mixture of sodium salt (2 mmol) and tetrabutylammonium bromide (TBAB) (0.25 mmol) in water (5.0 mL),
a-bromoketone (1.0 mmol) was added and magnetically stirred for the time shown in Table 1. After completion of
reaction, monitored by TLC (n-hexane:ethyl acetate; ratio = 5:1), the mixture extracted into ether (3 Â 5). The
combined organic layer washed with cold water (3 Â 10), dried over CaCl2 and then evaporated to dryness to give
desired product. All of the reactions reported here were pure as judged by TLC, FTIR and NMR analysis of the crude
reaction mixture. 1-(4-methoxyphenyl)-2-thiocyanatoethanone (entry 2b): IR (neat): n SCN (2157 cmÀ1); 13C NMR
(CDCl3, 100 MHz): d 42.9 (CH2), 55.7 (CH3O), 112.2 (SCN), 114.4 (m-C), 126.9 (C), 130.9 (O–C), 164.8 (p-C), 189.2
(CO); 2-iodo-1-(4-methoxyphenyl)ethanone (entry 2c): IR (neat): n C–I (615 cmÀ1); 13C NMR (CDCl3, 100 MHz): d
1.72 (CH2), 55.6 (CH3O), 114.3 (m-C), 126.3 (C), 130.6 (O–C), 164.0 (p-C), 191.5 (CO); 2-azido-1-(4-bromophenyl)
ethanone (entry 4a): IR (neat): n N3 (2103 cmÀ1); 13C NMR (CDCl3, 100 MHz): d 54.8 (CH2), 129.4–133.0 (Ar–C),
192.3(CO); 1-(4-bromophenyl)-2-thiocyanatoethanone (entry 4b): IR (neat): n SCN (2157 cmÀ1); 13C NMR (CDCl3,
100 MHz): d 42.6 (CH2), 111.5 (SCN), 129.8–132.6 (Ar–C), 189.8 (CO).
2. Results and discussion
In order to optimize the reaction condition and to evaluate catalytic activity of TBAB, 2-bromo-1-
phenylethanone were used as a model compound and reacted with sodium thiocyanate in water at room temperature.
According to thin-layer chromatographic analysis, the best results were obtained with the condensation of one mole
of the phenacyl bromide with 2 mol of NaSCN using 0.25 mol of TBAB in water. The catalyst acted very efficiently
and converted the entry to its corresponding 1-phenyl-2-thiocyanatoethanone in high isolated yield within

302
S. Sayyahi, J. Saghanezhad / Chinese Chemical Letters 22 (2011) 300–302
40 min. Table 1 shows the scope and limitations of these nucleophilic substitution reactions using several
a-bromoacetophenone derivatives.
The formation of products can be easily detected by the characteristic 13C absorption band of –SCN group for
phenacyl thiocyante at ꢀ112 and a-carbon in phenacyl azide and iodide that shift from ꢀ30 in phenacyl bromide to ꢀ
54 and ꢀ1.3 ppm, respectively. Although phenacyl thiocyantes, azides and iodides were obtained in high isolated
yields, phenacyl cyanides could only be obtained in moderate yields; because the reaction system becomes pasty so
hindering the completion of the reactions. These results are in agreement with the hard and soft acid and base principle
(HSAB) and the data acquired by Sukata for alkyl halides [18].
To evaluate the efficiency of this method for the scaling up experiment, transformation of 1-(4-methoxyphenyl)-2-
bromide was also performed on a 100 mmol scale. Gratifyingly, the substrate provided the corresponding phenacyl
derivatives without appreciable decrease in the yields.
In conclusion, we have reported here the use of tetrabutylammonium bromide as an efficient catalyst in the
synthesis of phenacyl derivatives in water. The reactions generated the corresponding products under mild conditions
and with satisfactory yields.
Acknowledgment
Partial support for this work by Islamic Azad University, Mahshahr branch research council is gratefully
acknowledged.
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