A simple and convenient method for preparation of carboxylic acid alkyl esters, phenolic and thioesters using chlorodiphenylphosphine/I2 and imidazole reagent system

Article abstract of DOI:10.1016/j.tet.2010.10.022

Condensation of carboxylic acids with alcohols, phenols and thiols proceeded smoothly to afford carboxylic acid alkyl esters, phenolic esters and thioesters by using the combination of chlorodiphenylphosphine, imidazole and molecular iodine in refluxing acetonitrile. Esterification with this mixed reagent system gave the corresponding products in excellent yields. The phosphorus-containing byproduct was simply removed from the organic phase by basic aqueous workup without the need for chromatography purification.

Full text of DOI:10.1016/j.tet.2010.10.022

Tetrahedron 66 (2010) 9596e9601
Contents lists available at ScienceDirect
Tetrahedron
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A simple and convenient method for preparation of carboxylic acid alkyl esters,
phenolic and thioesters using chlorodiphenylphosphine/I2 and imidazole reagent
system
*
Najmeh Nowrouzi , Abdol Mohammad Mehranpour, Javad Ameri Rad
Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 April 2010
Received in revised form 18 September 2010
Accepted 11 October 2010
Available online 15 October 2010
Condensation of carboxylic acids with alcohols, phenols and thiols proceeded smoothly to afford carboxylic
acid alkyl esters, phenolic esters and thioesters by using the combination of chlorodiphenylphosphine,
imidazole and molecular iodine in refluxing acetonitrile. Esterificationwith this mixed reagent system gave
the corresponding products in excellent yields. The phosphorus-containing byproduct was simply removed
from the organic phase by basic aqueous workup without the need for chromatography purification.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Esterification
Alkyl esters
Phenolic esters
Thioesters
Chlorodiphenylphosphine
Iodine
1. Introduction
phosphine,6 polystyryldiphenylphosphine,7 diphenyl(2-pyridyl)-
phosphine,8 (4-dimethylaminophenyl)diphenylphosphine,9 Sil-
Esterification reactions are among the oldest and most often used
reactionsinorganic chemistrywith wideapplications inchemicaland
pharmaceuticalindustries.1 Duetotheimportanceofesters, theyhave
been the subject of extensive experimental studies and
many synthetic methods have been employed in the synthesis of
these compounds.2 In 1967 Oyo Mitsunobu reported a method for
the condensation of a carboxylic acid and alcohol, using a mixture
of triphenylphosphine (Ph3P) and diethyl azodicarboxylate (DEAD),
to provide an ester.3 In recent years also, new azo and phosphorus-
based reagents are the most commonly used for this purpose.4
A major difficulty experienced with these reagent systems is due to
the fact that triphenylphosphine and its oxide are difficult to remove
from the reaction mixture and careful chromatography is usually re-
quired to isolate the pure product from the unreacted reagent and
byproduct, which usually results in reduced yield. This is especially
inconvenient in large-scale synthesis. Therefore, many efforts have
been directed towards modifying Ph3P reagent to facilitate the
isolation and purification of a desired product. Polymer-supported
triphenylphosphine,5 PEG-supported (PEG¼polyethyleneglycol)
phos,10 are among the recently examples of the useful phosphines.
However, recently, focus has shifted away from the development of
alternative reagents for the facilitation of the purification of products.
This is probably due to the fact that most of the alternative reagents
reported in the literature are not commercially available and required
multistep synthetic sequences for their preparation.
2. Results and discussion
As mentioned above, due to the problems encountered with
isolation process of the byproduct phosphine oxide, and great at-
tention in using commercially available reagents, we report on the
use of chlorodiphenylphosphine (CDP) in conjunction with mo-
lecular iodine to perform a very clean and efficient esterification
reaction. In this system, the resulting phosphorus byproduct,
diphenylphosphinic acid, can be extracted with an aqueous basic
solution in the workup processes.
To find the optimized condition, benzylation of benzoic acid was
first tried in toluene at room temperature and also under reflux
conditions using Ph2PCl, I2 and imidazole and the desired ester,
benzyl benzoate, was obtained in quantitative yield (Table 1). Next,
we used other organic solvents, such as acetonitrile, dichloro-
methane and ethyl acetate at different temperatures to find the
* Corresponding author. Tel.: þ98 771 4222341; fax: þ98 771 4541494; e-mail
address: nowrouzi@pgu.ac.ir (N. Nowrouzi).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.022

N. Nowrouzi et al. / Tetrahedron 66 (2010) 9596e9601
9597
Table 1
Table 3
Effect of solvent and temperature on benzylation of benzoic acid using Ph2PCl, I2 and
imidazole system
Condensation of carboxylic acids with different alcohols in the presence of Ph2PCl/I2/
imidazole in CH3CNa
Entry
Solvent
Condition
Time (h)
Conversion %
Entry
1
Acid
Alcohol
Time (h)
4
Yieldb
91
%
1
2
3
4
5
6
7
8
Toluene
Toluene
CH3CN
CH3CN
CH2Cl2
CH2Cl2
EtOAc
rt
reflux
rt
reflux
rt
reflux
rt
9
4
11
4
24
24
24
24
100
100
100
100
50
70
Trace
30
2
3
4
4.5
2.5
5
88
89
90
EtOAc
reflux
most suitable condition for the reaction. The results of this study
are summarized in Table 1.
According to the results obtained, when the reaction was tried in
toluene or acetonitrile at reflux, no significant difference was ob-
served and benzyl benzoate was obtained quantitatively in shorter
reaction time (Table 1, entries 2 and 4), but for more safety and
convenient workup, acetonitrile was used as the most suitable
solvent for this reaction. The obtained results of entries 3 and 4
shows that heating of the reaction mixture has pronounced effect
on the rate of this transformation.
We also examined the effect of different ratios of Ph2PCl/imid-
azole/I2/RCO2H/ROH in CH3CN at reflux for the conversion of ben-
zoic acid to benzyl benzoate. Employing the ratio of 1:3:1:2.1:2
gave the best result and produced the product after 4 h in 91%
isolated yield (Scheme 1).
5
6
7
8
9
1.5
3
92
92
90
88
93
4.5
5.5
2
O
O
Ph2PCl (1 eq), I2 (1 eq)
imidazole ( 3 eq)
OH
OH
O
+
CH3CN, reflux
4 h
2 eq
2.1 eq
91 %
Scheme 1.
Other bases, such as triethylamine, pyridine and 4-dimethyl-
amino pyridine (DMAP) were also examined. There was no ester
formation between benzoic acid and benzyl alcohol in the presence
of triethylamine or pyridine (Table 2, entries 3 and 4) even under
reflux conditions. Performing this transformation using DMAP in-
stead of imidazole, required a longer reaction time (Table 2, entry 5).
These results show the higher efficiency of imidazole for this
transformation. Moreover, this conversion was unsuccessful in the
absence of imidazole (entry 1). It seems that imidazole not only
neutralizes the liberated halogen acids but also enhances the re-
activity of the reagent system. It has the additional advantage of
being only sparingly soluble in organic solvent but freely soluble in
water and is thus extracted from the organic phase by using either
acidic or basic aqueous workup.
10
11
3
1
89
93
12
24
d
a
Reflux condition.
Isolated yield.
b
Table 2
Conversion of benzoic acid to benzyl benzoat using Ph2PCl/I2 in the presence of
different bases in refluxing acetonitrile
withdrawing substituent (entry 5) reacted in shorter time. As
expected, the presence of the nitro group on aromatic ring
(stronger aryl acids) is very effective in activating the carboxylic
group towards reaction with alcohol compared to weaker acids,
such as benzoic and 4-methylbenzoic acid.
As indicated in Table 3, this reagent system is suitable for the
conversion of primary and secondary aliphatic and also benzylic
alcohols to their corresponding esters. The reaction with primary
alcohols is somewhat faster in comparison with the reactions when
more bulky secondary ones are used (Table 3, entries 7 and 8). As
predicted, tertiary alcohols were resistant to esterification. This is
probably due to steric effects (Table 3, entry 12). It is obvious that
both electron-rich and electron-poor benzylic alcohols (entries 2
and 6) gave excellent yields of their corresponding esters.
Entry
Base
Time (h)
Conversion %
1
2
3
4
5
d
24
4
24
24
7
d
Imidazole
Et3N
Py
100
d
d
DMAP
100
After optimization, we examined a variety of primary, second-
ary, tertiary and benzylic alcohols and various aliphatic and
aromatic carboxylic acids carrying electron-donating and electron-
withdrawing groups and the optimized reaction conditions were
applied to these substrates (Table 3).
Carboxylic acids having deactivated and activated aromatic
rings (entries 1 and 4) afforded the corresponding esters in high
yields after 4e5 h, whereas carboxylic acid having electron-
We also examined propionic acid as an aliphatic carboxylic acid
in this system. The results showed that aliphatic acids could be
cleanlyreacted similar tothe reactionwith aromatic acids (entry 10).

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N. Nowrouzi et al. / Tetrahedron 66 (2010) 9596e9601
Also with this reagent system, no incorporation of chloride and
iodide into the products was observed during the esterification
reaction.
As shown in this Table, esterification of various phenols
(2.0 equiv) was examined in acetonitrile under reflux conditions
with 1.0 equiv of Ph2PCl, 3.0 equiv of imidazole and 1.0 equiv of I2.
Phenols, which have electron-donating or electron-withdrawing
groups reacted smoothly under mild conditions to afford the cor-
responding esters in high yields.
The reactions of benzoic acid with electron-rich phenols, such as
4-methoxyphenol (entry 3) was successful and gave the 4-
methoxyphenylbenzoatein 93% yields after 70min, but lower yields
and longer reaction times were observed from phenols bearing
electron-withdrawing groups on phenyl moiety (entries 5 and 6). In
addition to the electronic factors, steric factors also affected the re-
action in terms of time and yield. Comparison of entries 5 and 6
indicate that existence of ortho substituent on the phenol ring,
slightly decrease the yield and increase the time of the reaction.
Based on the above results, a proposed reaction mechanism is
shown in Scheme 3.
We also used finely powdered ammonium acetate instead of
acetic acid and imidazole in the reaction mixture. For this purpose,
a mixture of Ph2PCl/NH4OAc/I2 (1:2.1:1) was well stirred in aceto-
nitrile at reflux. Benzyl alcohol (2 mmol) was then added to this
mixture. We found that in this case the esterification reaction did
not occur and no benzyl acetate was formed even after 24 h. This
result shows the higher efficiency of our new reagent system for
this conversion.
Having success for esterification of carboxylic acids using alco-
hols, we sought to extend this methodology to the direct prepa-
ration of phenolic esters from carboxylic acids and phenols. So, the
condensation reaction between carboxylic acids with phenols was
carried out to afford the desired products (Scheme 2).
OH
O
O
Ph2PCl, I2 , imidazole
CH3CN, reflux
Cl
H
+
R
O
R
OH
Z
Z
N
N
H
I
R = Alkyl and aryl
Z = H, electron with-drawing and electron-donating groups
Ph2P
Ph2P
I2
N
N
HN
N
N
N
Ph2PCl
+
Scheme 2.
I
We found that molar ratios of 1:3:1:2.1:2 for Ph2PCl/imidazole/
I2/RCO2H/ArOH gave the best results for this condensation. Con-
sistent with our previous optimization reactions, acetonitrile was
chosen as solvent in reflux condition. We then applied this opti-
mized conditions for the synthesis of phenolic esters. The obtained
results are shown in Table 4.
(I)
(II)
I
H
N
N
H
O
Ph
P
O
RCO2R'
+
Ph2P(O)OH
R'OH
R
O
O
R
Ph
HN
N
Table 4
RCO2H
+
Synthesis of phenolic esters by Ph2PCl/imidazole/I2 system in CH3CN under reflux
(III)
Entry
1
Acid
Phenol
Time
Yielda
%
Scheme 3.
1-(Diphenylphosphino)imidazole (I) is formed in situ by adding
imidazole to Ph2PCl. Phosphine I can react with iodine to form in-
termediate phosphonium salt II, which then transforms to the
acyloxyphosphonium ion (III) by the attack of the more nucleo-
philic carboxylate anion at the phosphorus centre. Finally the attack
of the alcohol at the carbonyl carbon atom of the intermediate III
affords the corresponding carboxylic acid ester along with diphe-
nylphosphinic acid as shown in Scheme 3.
2 h
85
2
2.5 h
80
3
4
5
6
70 min
55 min
4.5 h
93
90
82
75
The phenolic esters are surely obtained in this way. But in order
to have more evidence in support of the proposed mechanism in
the case of alkyl esters, the stereochemistry of the reaction was
studied using chiral secondary alcohol (R)-(þ)-1-phenylethanol.
From the reaction of chlorodiphenylphosphine, imidazole, mo-
lecular iodine, benzoic acid and (R)-1-phenylethanol in refluxing
acetonitrile, (R)-1-phenylethyl benzoate was obtained in excellent
yield (93%) after 1 h (Table 3, entry 11). The complete stereo-
chemical retention proved by the optical rotation of (R)-1-phenyl-
ethyl benzoate.4c,11
The observed configuration is thought to arise through the acid
activation as acyloxyphosphonium salt III and direct attack of the
alcohol at the carbonyl carbon atom of this intermediate, which
supports the proposed mechanism shown in the Scheme 3.
In addition to stereochemistry, the reaction of a carboxylic acid
and thiol, could also confirm the proposed mechanism. In this way,
benzyl mercaptane (2 mmol, 0.234 mL) was added to a mixture of
chlorodiphenylphosphine (1 mmol, 0.18 mL), imidazole (3 mmol,
0.2 g), iodine (1 mmol, 0.254 g) and benzoic acid (2.1 mmol, 0.25 g)
in acetonitrile (5 mL) at reflux. After 4 h, S-benzyl benzothioate was
obtained in 80% yield. Formation of thioester, is consistent with the
existence of intermediate III in the reaction mixture.
5 h
7
40 min
88
81
8
1 h
a
Isolated yield.

N. Nowrouzi et al. / Tetrahedron 66 (2010) 9596e9601
9599
After the successful transformation of benzyl mercaptane to its
3. Experimental section
corresponding thioester, in order to increase the scope of the
present method and owing to the importance of thioesters12 es-
pecially in the protection of thiols, we decided to employ our new
reagent system for the synthesis of thioesters. Further results,
showed that the syntheses of various thioesters were performed
successfully under similar reaction conditions as used for alcohols.
The obtained results are shown in Table 5.
3.1. Typical procedure for the conversion of benzoic acid to
benzyl benzoate4c
To
a flask containing a stirred mixture of chlorodi-
phenylphosphine (1 mmol, 0.18 mL), imidazole (3 mmol, 0.2 g)
and iodine (1 mmol, 0.254 g) in acetonitrile (5 mL), was added
benzoic acid (2.1 mmol, 0.25 g) at reflux condition. Benzyl alcohol
(2.0 mmol, 0.2 mL) was then added to the reaction mixture. TLC
monitoring showed the completion of the reaction after 4 h. The
solvent was evaporated and the residue was dissolved in CH2Cl2
(10 mL) and washed with saturated aqueous sodium carbonate
(3ꢀ5 mL) to remove all diphenylphosphinic acid from the organic
phase. The aqueous phase was separated and the organic phase
was washed with aqueous sodium thiosulfate (2ꢀ5 mL) to
remove the excess iodine and then washed with water (10 mL),
dried and concentrated. The residue was subjected to flash
chromatography over silica gel by using n-hexane/ethyl acetate
(4:1) as eluent to give the benzyl benzoate (0.386 g, 91%) as
a colourless oil; dH (250 MHz, CDCl3) 7.98 (2H, dd, J 8.4, 1.5 Hz,
Ph), 7.44e7.24 (8H, m, Ph), 5.26 (2H, s, CH2); dC (62.9 MHz, CDCl3)
166.4, 136.1, 133.1, 130.2, 129.7, 128.6, 128.4, 128.3, 128.2, 66.7
(Table 3, entry 1).
Table 5
Preparation of thioesters using Ph2PCl/imidazole/I2 system in refluxing acetonitrile
Entry
1
Acid
Thiol
Time
Yielda
%
4 h
80
2
3
1 h
90
91
1.5 h
4
40 min
95
3.1.1. 4-Chlorobenzyl benzoate4a. Yield (0.434 g, 88%); dH (250 MHz,
CDCl3) 7.95 (2H, d, J 8.5 Hz, Ph), 7.44e7.41 (1H, m, Ph), 7.35e7.22
(6H, m, Ph), 5.21 (2H, s, CH2); dC (62.9 MHz, CDCl3) 166.3, 134.6,
134.1, 133.2, 129.9, 129.7, 129.6, 128.8, 128.4, 65.9 (Table 3, entry 2).
5
6
40 min
90
87
3.1.2. Phenethyl benzoate4c. Yield (0.402 g, 89%) as a colourless oil;
dH (250 MHz, CDCl3) 8.01 (2H, dd, J 7.0, 1.5 Hz, Ph), 7.52 (1H, t, J
7.5 Hz, Ph), 7.44e7.38 (2H, m, Ph), 7.32e7.22 (5H, m, Ph), 4.53 (2H, t,
J 7.1 Hz, OCH2), 3.04 (2H, t, J 7.0 Hz, CH2Ph); dC (62.9 MHz, CDCl3)
166.5, 137.9, 133.4, 132.9, 130.3, 130.1, 129.5, 129.3, 129.0, 128.6,
128.4, 128.0, 126.6, 65.5, 35.3 (Table 3, entry 3).
100 min
7
2 h
90
88
3.1.3. Benzyl-4-methylbenzoate4c. Yield (0.407 g, 90%) as a colour-
less oil; dH (250 MHz, CDCl3) 7.95 (2H, d, J 8.1 Hz, Ph), 7.45e7.29
(5H, m, Ph), 7.21 (2H, d, J 7.9 Hz, Ph), 5.35 (2H, s, CH2), 2.38 (3H, s,
Me); dC (62.9 MHz, CDCl3) 163.0, 143.7, 136.2, 133.3, 133.0, 129.8,
129.1, 128.6, 128.2, 128.1, 127.6, 127.4, 127.0, 66.5, 21.7 (Table 3,
entry 4).
8
70 min
a
Isolated yield.
From the results of Table 5, it was found that, factors, such as
electron deficiency of carboxylic acid and the steric bulk of thiols
have a profound effect on the time of reaction. As expected,
according to the mechanism, stronger aryl acids, such as 4-nitro-
benzoic acids, results in shorter reaction time (Table 5, entries 4 and
8) compared to weaker acids, such as benzoic and 4-methylbenzoic
acids (entries 2, 6 and 3,7). The effect of steric bulk is similar to that
carried out for alcohols. Primary thiols reacted faster in comparison
with secondary ones (entries 2e4 compared to entries 6e8).
In conclusion, a simple, efficient and convenient method for
preparation of carboxylic acid alkyl esters, phenolic esters and also
thioesters from carboxylic acids and various benzylic, primary and
secondary alcohols or thiols or phenols was established. The desired
products were prepared easily from chlorodiphenylphosphine and
iodine in the presence of imidazole in excellent yields. Chlor-
odiphenylphosphine is commercially available and inexpensive,
making large-scale esterification using this reagent system espe-
cially attractive. This system has the further advantage that the
resulting phosphorus byproduct, diphenylphosphinic acid, can be
extracted with base during product workup, which provides quicker
workup procedures instead of using the tedious and time-con-
suming chromatographic methods.
3.1.4. Benzyl-4-nitrobenzoate4c. Yield (0.473 g, 92%) as a yellow
solid, mp 79e82 ꢁC (lit.13 83e84 ꢁC); dH (250 MHz, CDCl3)
8.32e8.25 (4H, m, Ph), 7.46e7.36 (5H, m, Ph), 5.40 (2H, s, CH2); dC
(62.9 MHz, CDCl3) 164.5, 150.6, 135.5, 135.3, 130.8, 130.0, 128.7,
128.6, 128.4, 123.5, 67.6 (Table 3, entry 5).
3.1.5. 4-Methoxybenzyl benzoate4c. Yield (0.445 g, 92%) as a colour-
less oil; dH (250 MHz, CDCl3) 8.04 (2H, d, J 8.2 Hz, Ph), 7.51e7.48 (1H,
m, Ph), 7.42e7.35 (4H, m, Ph), 6.88 (2H, d, J 6.6 Hz, Ph), 5.28 (2H, s,
CH2), 3.78 (3H, s, OMe); dC (62.9 MHz, CDCl3) 166.5, 159.7, 147.6,
133.4, 130.5, 130.1, 129.7, 128.7, 114.0, 66.5, 55.3 (Table 3, entry 6).
3.1.6. Octyl benzoate4a. Yield (0.421 g, 90%); dH (250 MHz, CDCl3)
8.04 (2H, d, J 7.0 Hz, Ph), 7.54e7.39 (3H, m, Ph), 4.34 (2H, t, J 6.7 Hz,
OCH2), 1.79e1.70 (2H, m, OCH2CH2), 1.46e1.28 (10H, m, (CH2)5Me),
0.88 (3H, t, J 6.9 Hz, Me); dC (62.9 MHz, CDCl3) 166.7, 132.8, 130.53,
129.5, 128.3, 65.1, 31.8, 29.6, 29.2, 29.2, 28.7, 26.0, 22.6, 18.5, 14.1
(Table 3, entry 7).
3.1.7. 2-Octyl benzoate4a. Yield (0.412 g, 88%); dH (250 MHz, CDCl3)
8.04 (2H, d, J 7.0 Hz, Ph), 7.54e7.39 (3H, m, Ph), 5.21e5.09 (1H, m,
OCH), 1.70e1.59 (2H, m) 1.42e1.25 (11H, m), 0.87 (3H, t, J 6.9 Hz,

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N. Nowrouzi et al. / Tetrahedron 66 (2010) 9596e9601
CH2Me); dC (62.9 MHz, CDCl3) 166.2, 132.7, 130.9, 129.5, 128.3, 71.7,
36.1, 31.7, 29.2, 25.4, 22.6, 20.1, 14.1 (Table 3, entry 8).
163.7, 157.6, 150.8, 144.0, 135.0, 131.2, 123.7, 122.2, 114.6, 55.6 (Table
4, entry 7).
3.1.8. 2-Octyl 4-nitrobenzoate4a. Yield (0.520 g, 93%); dH
(250 MHz, CDCl3) 8.30e8.18 (4H, m, Ph), 5.25e5.13 (1H, m, OCH),
1.81e1.57 (2H, m), 1.39e1.28 (11H, m), 0.86 (3H, t, J 6.6 Hz,
CH2Me); dC (62.9 MHz, CDCl3) 164.3, 150.4, 136.3, 130.6, 123.4,
73.1, 35.9, 31.7, 29.3, 29.1, 28.6, 25.7, 25.3, 22.5, 19.9, 14.0 (Table 3,
entry 9).
3.2.6. 4-Methoxyphenyl-propanoate4a. Yield (0.292 g, 81%); dH
(250 MHz, CDCl3) 6.88 (2H, d, J 8.0 Hz, Ph), 6.77 (2H, d, J 8.8 Hz, Ph),
3.68 (3H, s, OMe), 2.47 (2H, q, J 7.5 Hz, CH2Me), 1.16 (3H, t, J 7.5 Hz,
CH2Me); dC (62.9 MHz, CDCl3) 173.3, 157.2, 144.3, 122.3, 114.4, 55.52,
27.7, 9.1 (Table 4, entry 8).
3.3. Typical procedure for the conversion of benzoic acid to
3.1.9. Benzyl propionate4c. Yield (0.292 g, 89%); dH (250 MHz,
CDCl3) 7.34e7.15 (5H, m, Ph), 5.03 (2H, s, CH2Ph), 2.28 (2H, q, J
7.5 Hz, CH2Me), 1.07 (3H, t, J 7.5 Hz, Me); dC (62.9 MHz, CDCl3) 174.3,
136.1, 128.5, 158.2, 127.8, 66.1, 27.6, 9.1 (Table 3, entry 10).
S-benzyl benzothioate4a
A mixture of chlorodiphenylphosphine (1 mmol, 0.18 mL), im-
idazole (3 mmol, 0.2 g) and iodine (1 mmol, 0.254 g) in acetonitrile
(5 mL) was stirred at reflux conditions. Then 2.1 mmol of benzoic
acid (0.25 g) and 2.0 mmol of benzyl mercaptane (0.234 mL) were
added to the resulting mixture. After completion of the reaction as
monitored by TLC (4 h), the solvent was evaporated and CH2Cl2
(10 mL) was added. The organic layer was washed with saturated
aqueous sodium carbonate (3ꢀ5 mL) and aqueous sodium thio-
sulfate (2ꢀ5 mL), respectively, and dried. The pure product was
obtained after flash chromatography of the crude mixture on silica
gel using n-hexane/ethyl acetate (4:1) as eluent (0.365 g, 80%) as
a white solid, mp 37 ꢁC (lit.4a 36.6e36.7 ꢁC); dH (250 MHz, CDCl3)
7.87 (2H, dd, J 7.1, 1.4 Hz, Ph), 7.47e7.15 (8H, m, Ph), 4.23 (2H, s,
CH2); dC (62.9 MHz, CDCl3) 191.7, 137.5, 133.5, 129.3, 129.0, 128.7,
128.7, 128.5, 128.4, 128.2, 127.3, 127.3, 33.3 (Table 5, entry 1).
3.1.10. (R)-1-phenylethyl benzoate11. Yield (0.420 g, 93%) as a col-
ourless oil; dH (250 MHz, CDCl3) 8.00 (2H, d, J 8.4 Hz, Ph), 7.40e7.26
(8H, m, Ph), 6.05 (1H, q, J 6.5 Hz, CHPh), 1.60 (3H, d, J 6.5 Hz, Me)
(Table 3, entry 11).
3.2. Typical procedure for the conversion of benzoic acid to
phenyl benzoate4a
Benzoic acid (2.1 mmol, 0.25 g) was added to a stirred mixture
of chlorodiphenylphosphine (1 mmol, 0.18 mL), imidazole
(3 mmol, 0.2 g) and iodine (1 mmol, 0.254 g) in acetonitrile (5 mL)
at reflux. Phenol (2 mmol, 0.188 g) was then added to the reaction
mixture. After the appropriate reaction time for the completion of
the conversion (2 h), the solvent was evaporated on a rotary
evaporator and the residue was dissolved in CH2Cl2 (10 mL). The
organic layer was washed with saturated aqueous sodium car-
bonate (3ꢀ5 mL) followed by aqueous sodium thiosulfate
(2ꢀ5 mL) and dried. Flash chromatography of the organic residue
was performed on silica gel using n-hexane/ethyl acetate (4:1) as
eluent to give the pure phenyl benzoate (0.337 g, 85%) as a yel-
lowish powder, mp 64e68 ꢁC (lit.14 66e69 ꢁC); dH (250 MHz,
CDCl3) 8.19e8.15 (2H, d, J 8.2 Hz, Ph), 7.78e7.06 (8H, m, Ph); dC
(62.9 MHz, CDCl3) 165.1, 151.2, 133.7, 129.9, 129.6, 129.3, 128.7,
125.8, 121.5 (Table 4, entry 1).
3.3.1. Pentyl benzothioate4a. Yield (0.375 g, 90%); dH (250 MHz,
CDCl3) 8.21 (2H, d, J 8.5 Hz, Ph), 8.03 (2H, d, J 8.4 Hz, Ph), 3.04 (2H, t, J
7.5 Hz, SCH2), 1.64e1.59 (2H, m, SCH2CH2), 1.32e1.27 (4H, m,
CH2CH2Me), 0.84 (3H, t, J 6.4 Hz, Me); dC (62.9 MHz, CDCl3) 190.5,
150.4,141.8,128.2,123.8, 31.0, 29.6, 29.0, 22.2,13.9 (Table 5, entry 2).
3.3.2. Pentyl 4-methylbenzothioate4a. Yield (0.404 g, 91%); dH
(250 MHz, CDCl3) 7.78 (2H, d, J 8.2 Hz, Ph), 7.15 (2H, d, J 8.2 Hz, Ph),
2.97 (2H, t, J 7.3 Hz, SCH2), 2.31 (3H, s, Me), 1.62e1.15 (2H, m,
SCH2CH2), 1.36e1.23 (4H, m, CH2CH2Me), 0.83 (3H, t, J 6.9 Hz,
CH2Me); dC (62.9 MHz, CDCl3) 191.7, 144.0, 134.8, 129.2, 127.2, 31.1,
29.3, 28.9, 22.2, 21.6, 13.9 (Table 5, entry 3).
3.2.1. 4-Methoxyphenyl benzoate4a. Yield (0.424 g, 93%); dH
(250 MHz, CDCl3) 8.10 (2H, dd, J 8.4, 1.3 Hz, Ph), 7.52e7.49 (1H, m,
Ph), 7.39 (2H, t, J 8.0 Hz, Ph), 7.04 (2H, dd, J 8.7, 1.8 Hz, Ph), 6.84 (2H,
dd, J 8.9, 1.7 Hz, Ph), 3.73 (3H, s, OMe); dC (62.9 MHz, CDCl3) 165.6,
157.3, 144.4, 133.5, 130.1, 129.6, 128.6, 122.5, 114.5, 55.6 (Table 4,
entry 3).
3.3.3. Pentyl 4-nitrobenzothioate4a. Yield (0.481 g, 95%); dH
(250 MHz, CDCl3) 7.89e7.30 (4H, m, Ph), 2.97 (2H, t, J 7.2 Hz, SCH2),
1.58e1.55 (2H, m, SCH2CH2), 1.34e1.27 (4H, m, CH2CH2Me), 0.82
(3H, t, J 6.5 Hz, Me); dC (62.9 MHz, CDCl3) 192.0, 137.3, 135.5, 134.2,
133.2, 130.5, 128.4, 31.0, 29.6, 28.9, 22.2, 13.9 (Table 5, entry 4).
3.2.2. 4-Bromophenyl benzoate4a. Yield (0.500 g, 90%); dH (250 MHz,
CDCl3) 8.03 (2H, dd, J 7.8,1.5Hz, Ph), 7.50 (1H, m, Ph), 7.40 (4H, m, Ph),
7.00 (2H, dd, J 6.8, 2.0 Hz, Ph); dC (62.9 MHz, CDCl3) 164.9, 150.0,
133.8, 132.5, 130.2, 129.2, 128.7, 123.6, 119.0 (Table 4, entry 4).
3.3.4. Pentyl propanthioate4a. Yield (0.288 g, 90%); dH (250 MHz,
CDCl3) 3.43 (2H, m, SCH2), 2.46 (2H, q, J 7.5 Hz CH2CO), 1.85e1.84
(2H, m, SCH2CH2), 1.62e1.60 (4H, m, CH2CH2Me), 1.38e1.05 (6H, m,
Me) (Table 5, entry 5).
3.2.3. 4-Nitrolphenyl benzoate4a. Yield (0.400 g, 82%); dH (250 MHz,
CDCl3) 8.24 (2H, d, J 8.4 Hz, Ph), 8.11 (2H, d, J 7.1, Ph), 7.61 (1H, m,
Ph), 7.46 (2H, t, J 7.8 Hz, Ph), 7.34 (2H, dd, J 7.0, 2.1 Hz, Ph); dC
(62.9 MHz, CDCl3) 164.3, 156.9, 144.5, 133.4, 132.8, 128.6, 125.9,
125.0, 119.3 (Table 4, entry 5).
3.3.5. S-Cyclohexyl benzothioate4a. Yield (0.383 g, 87%); dH
(250 MHz, CDCl3) 7.86 (2H, d, J 7.2 Hz, Ph), 7.48e7.15 (3H, m, Ph),
3.69e3.59 (1H, m, SCH), 1.69e1.21 (6H, m, cyclohexyl ring),
1.97e1.90 (4H, m, cyclohexyl ring) (Table 5, entry 6).
3.3.6. S-Cyclohexyl 4-methylbenzothioate4a. Yield (0.421 g, 90%); dH
(250 MHz, CDCl3) 7.84 (2H, d, J 8.2 Hz, Ph), 7.22 (2H, d, J 8.0 Hz, Ph),
3.75e3.66 (1H, m, SCH), 2.39 (3H, s, Me), 2.05e1.98 (2H, m, cyclo-
hexyl ring), 1.78e1.71 (2H, m, cyclohexyl ring), 1.60e1.45 (6H, m,
cyclohexyl ring); dC (62.9 MHz, CDCl3) 191.5,143.9,129.1,127.2, 42.4,
33.2, 26.0, 25.6, 21.6 (Table 5, entry 7).
3.2.4. 2-Nitrolphenyl benzoate4a. Yield (0.365 g, 75%); dH (250 MHz,
CDCl3) 8.12e8.08 (2H, m, Ph), 7.59e7.54 (2H, m, Ph), 7.45e7.39 (5H,
m, Ph); dC (62.9 MHz, CDCl3) 164.4, 144.31, 134.8, 134.2, 130.5, 130.2,
128.7, 128.4, 126.7, 125.8, 125.3 (Table 4, entry 6).
3.2.5. 4-Methoxyphenyl-4-nitrobenzoate4a. Yield (0.480 g, 88%); dH
(250 MHz, CDCl3) 8.30e8.27 (4H, m, Ph), 7.07 (2H, d, J 9.1 Hz, Ph),
6.88 (2H, d, J 9.1 Hz, Ph), 3.73 (3H, s, OMe); dC (62.9 MHz, CDCl3)
3.3.7. S-Cyclohexyl 4-nitrobenzothioate4a. Yield (0.466 g, 88%); dH
(250 MHz, CDCl3) 8.20 (2H, d, J 8.9 Hz, Ph), 8.02 (2H, d, J 8.9 Hz, Ph),

N. Nowrouzi et al. / Tetrahedron 66 (2010) 9596e9601
9601
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Acknowledgements
We thank the Persian Gulf University Research Council for gen-
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Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.10.022.
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