Practical preparation of esters and thioacetates from alkyl halides and carboxylates or thioacetate catalyzed by PEG400 without solvent

Article abstract of DOI:10.1080/00397910600941380

Carboxylic esters and thioacetates were conveniently prepared in good to excellent yields under mild conditions by the reaction of alkyl halides with sodium carboxylates or sodium thioacetate catalyzed by PEG400 in the absence of solvents. Copyright Taylor & Francis Group, LLC.

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Practical Preparation of Esters and
Thioacetates from Alkyl Halides and
Carboxylates or Thioacetate Catalyzed by
PEG400 without Solvent
a
a
a
a
a
Yu‐Qing Cao , Guo‐Qiang Wu , Ya‐Bin Li , Zhi Dai & Bao‐Hua Chen
a
College of Pharmacy, Hebei University , Baoding, China
Published online: 23 Nov 2006.
To cite this article: Yu‐Qing Cao , Guo‐Qiang Wu , Ya‐Bin Li , Zhi Dai & Bao‐Hua Chen (2006) Practical
Preparation of Esters and Thioacetates from Alkyl Halides and Carboxylates or Thioacetate Catalyzed by
PEG400 without Solvent, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 36:22, 3353-3358, DOI: 10.1080/00397910600941380
To link to this article: http://dx.doi.org/10.1080/00397910600941380
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Synthetic Communications , 36: 3353–3358, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600941380
Practical Preparation of Esters and
Thioacetates from Alkyl Halides and
Carboxylates or Thioacetate Catalyzed by
PEG400 without Solvent
Yu-Qing Cao, Guo-Qiang Wu, Ya-Bin Li, Zhi Dai, and
Bao-Hua Chen
College of Pharmacy, Hebei University, Baoding, China
Abstract: Carboxylic esters and thioacetates were conveniently prepared in good to
excellent yields under mild conditions by the reaction of alkyl halides with sodium
carboxylates or sodium thioacetate catalyzed by PEG400 in the absence of solvents.
Keywords: Alkyl halides, carboxylic esters, PEG400, solventless, thioacetates
INTRODUCTION
Carboxylic esters and thioesters were widely used as intermediates in organic
[1]
synthesis and as products in pharmaceutical and spice industries and had
attracted a great deal of attention. For example, they can be applied in the
[2]
synthesis of a,b-unsaturated esters and lactones under very mild conditions.
One of traditional methods for the preparation of carboxylic esters was the
reaction of an alcohol with a carboxylic acid, which usually was catalyzed
[3]
by acids. Long reaction times were needed. Another way to make esters
was to turn the acid into acyl chloride and then added the alcohol along
[
with base. On the other hand, the most traditional methods for the pre-
4]
[
5]
paration of thiolesters were the coupling of a thiol with a carboxylic acid
[6]
or an alcohol with a thiocarboxylic acid. However, the former strategy
Received in R.O.C. January 16, 2006
Address correspondence to Yu-Qing Cao, College of Pharmacy, Hebei University,
Baoding 071002, China. E-mail: pharm_hbu@yahoo.com
3
353

3
354
Cao and Wu
needs long reaction times and the latter needs the participation of
precious dehydrating agents such as dicyclohexylcarbodimide (DCC),
because of its small equilibrium constants.
The reaction of alkyl halides with sodium carboxylates or sodium thio-
acetate was a common method for the preparation of carboxylic esters or
[
7,8]
thioacetates.
The advantages of this reaction were shorter reaction times,
mild conditions, and higher yields. This method was especially applicable
for the preparation of carboxylic esters or thioacetates that had unsaturated
bonds, but the most of reactions were carried out in organic solvents. Devel-
oping green chemistry is one of the most important purposes of organic
synthesis at present. Organic synthesis in the absence of solvent was of
[
9,10]
great value.
In this respect, a method that involves the application of
readily available reagents, such as alkyl halides and sodium carboxylates or
sodium thioacetates in solvent-free conditions, should be interesting and
easily put into industrial production.
Polyethylene glycols (PEGs) could be regarded as the acyclic crown ether
and had been widely used as phase-transfer catalysts (PTC) in many organic
reactions owing to their stability, low cost, low toxicity, and easy avail-
[
11,12]
ability.
PEG with 7–9 units was more effective in catalyzing the
þ
reactions in which Na salts participated. Especially because of the liquid
property, perfect solubility in water, and the participation of two hydroxy
groups during the destructing crystal lattice of the solids, PEG400 was
more suitable for solid–liquid-phase solvent-free organic reactions. The
carboxylate anions or thioacetic anions could easily enter the liquid phase
and become strong nucleophilic reagents that could promptly undertake
nucleophilic substitution.
In continuation of our research on the use of PEGs as PTCs in organic
[
13–15]
synthesis without solvents,
we herein report a facile method for the
preparation of carboxylic esters or thioacetates by the reaction of alkyl
halides with sodium carboxylates or sodium thioacetate, catalyzed by
PEG400 in the absence of solvents (Scheme 1). The experimental results
are listed in Table 1.
Scheme 1.

Table 1. Esterification of sodium carboxylate with alkyl halides
Bp (8C/mmHg) or mp (8C)
Found Reported
Time
Yield
(%)
0
Entry
R
Alkyl halides
(h)
[16]
124–126/760
1
2
3
4
5
6
7
8
9
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
Ph-
Ph-
Ph-
Ph-
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
-
n-butyl-Cl
n-butyl-Br
n-butyl-I
5
89
90
90
92
91
68
41
85
94
86
77
81
90
95
88
89
87
88
90
86
76
90
82
81
124–125/760
-
4
-
2
[
[
[
17]
16]
16]
-
n-C
n-C
6
H
13Br
17Br
4
171–172/760
121–122/50
39–40/50
171–173/760
210–212/760
111–112/760
-
8
H
5
-
s-butyl-Br
t-butyl-Br
5
[
16]
-
7
30–31/50
87–88/50
98–99/760
[
[
[
16]
-
c-C
6
H
11-Br
CH Cl
55 CHCH
6
172–173/760
206–208/760
103–105/760
16]
17]
-
C
6
H
5
2
4.5
3
115–116/50
103–104/760
49–50
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
-
CH
2
2
Br
Br
OOCCH Br
[16]
-
C
C
6
H
H
5
COCH
2
2
49–51
[
[
[
[
[
[
[
17]
16]
16]
16]
16]
16]
16]
-
2
5
2
2.5
3.5
4
178–179/760
163–164/760
144–145/50
183–184/760
209–210/760
166–167/50
182–183/50
18–20
179–180/760
164–165/760
240–241/760
184–186/760
210–211/760
248–250/760
272–273/760
CH
CH
2
CH
CH
2
-
-
n-butyl-Br
CH Cl
55 CHCH
55 CHCH
2
2
C
6
H
5
2
(CH
(CH
2
)
)
4
5
-
-
CH
CH
2
2
Br
Br
4
2
2
2
5
n-butyl-Br
n-C 13Br
CH Cl
55 CHCH
5
6
H
6
[16]
C
6
H
5
2
6.5
4
19–20
243–244/760
[17]
CH
2
2
Br
162–163/50
36–37
[17]
p-NO
p-CH
furfuryl
OCH 55 CH-
2
C
6
H
4
-
n-butyl-Br
n-butyl-Br
10
37–38
184–185/40
[
17]
3
OC
6
H
4
-
4
5
4
183–184/40
110–111/50
109–110/50
[
17]
C
C
2
H
H
5
Br
Br
196–197/760
195–195/760
[17]
2 5
C H
2
5

3
356
Cao and Wu
RESULTS AND DISCUSSION
Taking the reaction of sodium acetate and benzyl chloride as an example, we
found that a yield as low as 67% was obtained after the reaction was
performed over 12 h without the presence of PEG400. However, when
3
mol% of PEG400 was added, the reaction period was greatly shortened,
and the yield was 94%. This amount, 3% mol of PEG400, was adequate to
catalyze the reaction effectively. The more PEG400 was employed, the
more products were lost during washing with water.
To shorten the reaction time, the reactions of sodium carboxylates and alkyl
halides were heated at 65–708C. As shown as in Table 1, the yield of n-butyl
acetate was slightly lower than benzyl acetate because some of esters with low
molecular weight were lost in the washing process. Longer reaction periods
were needed for the reactions of sodium benzoate than sodium acetate. The ester-
ification of sodium benzoate with electron-donating groups such as -OCH in the
3
aromatic ring and alkyl halides could be carried out in relatively shorter time than
with electron-withdrawing groups such as -NO . Especially for entries 11 and 12,
2
the yields were relatively lower, because some condensation products were
obtained as the high activity of the a-position of carbonyl group.
It can be inferred that alkyl iodide was more active than alkyl bromide,
which was also more active than alkyl chloride. We can consider the
mechanism as SN substitution reactions. Longer reaction time was needed for
2
cyclohexyl bromide because of the steric effect of the cyclohexyl ring. The
reaction of sodium acetate and s-butyl bromide could be carried out in lower
yields than n-butyl bromide, whereas very low yields were obtained in the
reactions of sodium acetate and t-butyl bromide. We proposed that the side
reaction of the competitive elimination for the t-butyl bromide and s-butyl
bromide might be the main reason for the low yields.
Table 2. Esterification of sodium thioacetate with alkyl halides
Bp (8C/mmHg) or mp (8)
Time
(h)
Yield
(%)
Entry
Alkyl halides
Found
Reported
[
18]
1
2
3
4
5
6
7
8
9
n-butyl-Cl
4
3
91
93
93
79
95
62
93
91
85
89
162–164/760 163–164/760
n-butyl-Br
n-butyl-I
c-C H -Br
1.5
5
[
18]
[
116–118/50
146–148/50
56–57/50
90–91/15
6
11
18]
n-C
t-butyl-Br
8
H
17-Br
4
128–131/24
[
18]
7
130/760
247–250/760
[
[
18]
18]
C H CH -Cl
6
3
160–162/50
5
2
CH
2
55 CH-CH
2
-Br
-Br
OOCCH
2
1.5
125–127/760 126–128/760
[
18]
C
C
6
H
H
5
COCH
2
130–132/50
82–83/50
108–110/18
64–65/18
[
18]
1
0
2
5
2
-Br 1.5

Practical Preparation of Esters and Thioacetates
3357
Based on the results listed in Table 2, the substitution of some alkyl
halides with sodium thioacetates could be carried out at room temperature,
and relatively higher yields could be obtained than with sodium acetates,
especially for entry 6 in Table 2. The reason was that thioacetic ion had
stronger nucleophilicity and weaker basicity than the carboxylic ion.
In conclusion, we have demonstrated a convenient and efficient method
for preparing esters or thioacetates from the corresponding alkyl halides and
sodium carboxylates or sodium thioacetate catalyzed by PEG400 without
solvent. The advantages of this procedure are higher yield, operational simpli-
city, low cost, and less pollution to environment. We assume that the method
is suitable for industrial application.
EXPERIMENTAL
GC-17A is a column packed with SE30 on Chromsorb using o-terphenyl as an
internal standard. Thin-layer chromatography was GF254 TLC with
petroleum ether/ethyl acetate (10/1) as eluent. Alkyl halides, sodium carbox-
ylate, sodium thioacetate, and PEG400 were commercially available and used
without further purification. Melting points were determined on a microscopy
apparatus and are uncorrected
Typical Procedure for the Preparation of Benzyl Acetate
A mixture of sodium acetate (18 g, 0.22 mol), benzyl chloride (25.4 g,
.2 mol), and PEG400 (2.4 g, 0.006 mol) was stirred in a 50 mL, three-
0
necked, round-bottomed flask equipped with a mechanical stirrer. Then the
mixture was vigorously stirred at 65–708C. The progress of the reaction
was monitored by TLC. Upon completion, the reaction mixture was washed
with 50 ml of water three times. The organic phase was separated and dried
over magnesium sulfate. Then 28.2 g of benzyl acetate were collected at
115–1168C/50 mmHg. Identification was based on comparison with
physical data reported in the literature.
Typical Procedure for the Preparation of Benzyl Thioacetate
A mixture of sodium thioacetate (21.6 g, 0.22 mol), benzyl chloride (25.4 g,
.2 mol), and PEG400 (2.4 g, 0.006 mol) was stirred in a 50 mL, three-
0
necked, round-bottomed flask equipped with a mechanical stirrer. Then the
mixture was vigorously stirred at room temperature. The progress of the
reaction was monitored by TLC. Upon completion, the reaction mixture
was washed with 50 ml of water three times. The organic phase was
separated and dried over magnesium sulfate. Then 31.9 g of benzyl thioacetate

3
358
Cao and Wu
was collected at 160–1628C/50 mmHg. The product was identified by
comparison with physical data reported in the literature.
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