Full text of DOI:10.1080/00397911.2018.1513532

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
A microwave-promoted atom-efficient
diesterification of aromatic carboxylate with 1,4-
dibromobutane in water
Shenglong Ding, Lin Bai, Yong Cong & Ting Chen
To cite this article: Shenglong Ding, Lin Bai, Yong Cong & Ting Chen (2018): A microwave-
promoted atom-efficient diesterification of aromatic carboxylate with 1,4-dibromobutane in water,
Synthetic Communications, DOI: 10.1080/00397911.2018.1513532
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https://doi.org/10.1080/00397911.2018.1513532
A microwave-promoted atom-efficient diesterification of
aromatic carboxylate with 1,4-dibromobutane in water
Shenglong Dinga, Lin Baib, Yong Conga, and Ting Chenb
b
aCollege of Chemistry and Engineering, Lanzhou University, Lanzhou, P. R. China; Institute of Green
Chemistry Experiment and Teaching, Lanzhou City University, Lanzhou, 730070, P. R. China
ABSTRACT
ARTICLE HISTORY
Received 26 March 2018
A rapid and efficient diesterification reaction of aromatic carboxylate
with 1,4-dibromobutane was carried out in water at 100ꢀC in
the presence of base and phase transfer catalyst under focused
microwave irradiation. This microwave-promoted protocol offers an
atom-efficient and environment-friendly approach to synthesize
butamethylenediesters in high yield.
KEYWORDS
1,4-dibromobutane; diesteri-
fication; focused microwave
irradiation; phase transfer
catalysis; water solvent
GRAPHICAL ABSTRACT
O
O
O
PTC, base, H2O
MW
+
2
Br(CH2)4Br
1
Ar
O
4
O
Ar
Ar
O-
2a-k
3a-k
Ar = -C6H5, -C6H4Br, -C6H4I, -C6H4NO2, -C6H4CH3, -C10H7, a-furan,
-CH2C6H5, -CH2C10H7, -CH=CHC6H5
Introduction
From the point of view of green chemistry’s interest, attention has been focused on
atom-economic reactions, environment-friendly solvents, and methodologies from both
academic and chemical industry.[1]
Water is unanimously viewed as an excellent green solvent. In particular, its hydro-
phobic effect and hydrogen-bonding capability would lead to a higher product yield and
a higher selectivity.[2] However, the less solubility of most organic substrates in water
disfavors many reactions. It has been opined that phase transfer catalysts (PTC) under
the microwave (MW) irradiation could be used to solve these problems.[3]
It has long been shown that MW irradiation has become an attractive technique for
accelerating organic synthesis. Microwave offers several advantages like fast heating
speed, high thermal efficiency, mild experimental conditions, simple operation, conveni-
ent control, environment protection, and low labor.[4]
The esterification reaction of carboxylic acid with alkyl halide is one of the
most important and commonly employed reactions in organic and bioorganic
CONTACT Shenglong Ding
disl@lzu.edu.cn
Department of Chemistry, Lanzhou University, P.O. Box: 730000,
Lanzhou, P. R. China
Supplemental data for this article can be accessed on the publisher’s website.
ß 2018 Taylor & Francis Group, LLC

2
S. DING ET AL.
synthesis.[5,6] Efforts have been made to replace the traditional synthesis of esters by
using Fischer’s method, catalyzed by a concentrated inorganic acid.[7] It has been well-
known for the formation of carboxylates by the reaction of metal salts of carboxylic
acids (RCOꢁ2 Mþ, where M may be silver, lead, one of the alkali or alkaline earth metals
or tertiary alkyl ammonium) and alkyl halides that the generally applicable synthetic
procedure is unfavorable, due principally to poor yields, resulting from the dehydroha-
logenation reactions. Although the procedure has been notably improved by alterna-
tively using polar aprotic solvents such as DMF, HMPA, DMSO or phase transfer
catalysts (PTC) of the quaternary alkyl ammonium,[5,6,8–10] these media offer some dis-
advantages like toxicity, harmfulness, costs, and hardness in the product isolation. In
addition, ionic liquids have successfully been utilized as catalysts or solvents in the reac-
tion of carboxylic acids with alkyl halides in high yield and higher selectivity.[10–16]
Methylene diesters of carboxylic acids and their derivatives are substantial products
or intermediates in the chemical and pharmaceutical industries.[17–19] The most
reported methods for synthesis of methylene diesters include the condensation of car-
boxylic acid with 1, n-diols,[20] or 1, n-dihaloalkanes,[16,21,22] acid chloride (acyl chlor-
ide) with 1,n-diols[23] and the transesterification.[24] Recently, an alternative procedure
for it to carry out the reaction in ionic liquids[16] or with the assistance of MW heating
was found.[23,25] Although methylene diesters are readily available, the main conven-
tional synthetic methods have several drawbacks such as longer reaction time, low
yields, the use of harmful solvents, and sensitive expensive catalysts, and a tedious
post-treatment.
In our recent work, we used water as the solvent, by coupling with PTC under MW
irradiation, in the esterification and etherification reaction of benzyl chloride and
p-hydroxy-benzoic acid.[26] This successful water-PTC-MW combination encouraged us
to develop a simple and novel method for the diesterification from carboxylic acids (or
their salts) and dihaloalkane.
Results and discussion
The one-pot esterification of carboxylic acid with alkyl halide in water was carried out
with two equivalents potassium salt of carboxylic acid in a focused MW synthesis sys-
tem, by which the reaction temperature, pressure, MW power, and reaction time were
easily controlled with a better reproducibility.
As a starting point, the diesterification was initially done using potassium benzoate
and 1,4-dibromobutane for optimizing its reaction conditions. A variety of bases were
applied. The MW irradiation temperature, time, the kind of base, and its amount were
investigated. Results are summarized in Table 1.
Table 1 indicates that the effect of bases on the reaction was significant (Table 1,
Entries 1–6). Desired diesterification products were not obtained in the absence of base.
By comparison, K2CO3, K3PO4, and Na2CO3 were more effective. Owing to its eco-
nomic and environment-friendly advantages, K2CO3 was selected as the base. It was
found that the amount of K2CO3 was still important (Table 1, Entries 3, 7–10). 1 mmol
of K2CO3 in 1 mL water worked most efficiently. The strength and concentration of
alkali also play a very important role. Weak alkalis were beneficial in proceeding

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SYNTHETIC COMMUNICATIONSV
3
Table 1. Optimization of reaction conditions of the diesterification of potassium benzoate with 1,4-dibromobutanea.
Entry
Base (mmol)
None
KOH (1 mmol)
K2CO3 (1mmol)
K3PO4 (1 mmol)
KF (1 mmol)
Na2CO3 (1mmol)
K2CO3 (0.5 mmol)
K2CO3 (0.75 mmol)
K2CO3 (1.25 mmol)
K2CO3 (1.5 mmol)
K2CO3 (1 mmol)
K2CO3 (1 mmol)
K2CO3 (1 mmol)
K2CO3 (1 mmol)
K2CO3 (1 mmol)
K2CO3 (1 mmol)
K2CO3 (1 mmol)
K2CO3 (1 mmol)
Time (min)
Temp (ꢀC)
Yield (%)b
1
2
3
4
5
6
7
8
30
30
30
30
30
30
30
30
30
30
30
30
30
30
25
28
32
35
100
100
100
100
100
100
100
100
100
100
80
Trace
57
92
89
85
90
84
88
90
87
86
91
86
82
64
81
83
67
9
10
11
12
13
14
15
16
17
18
90
110
120
100
100
100
100
aReaction conditions: potassium benzoate (5 mmol),1,4-dibromobutane (2.5 mmol), TBTA (1 mmol), water (1 mL). MW
power: 10 W.
bAverage isolated yield from twice reactions.
forward reactions, but the strong alkali such as KOH led to a dramatic decrease in the
yield of diesterification. The products were hydrolyzed.
The effects of temperature and time were then studied on the yield of diesterification.
The results are summarized in Table 1 (Entries 3, 11–18). The highest yield of 92% can
be obtained at 100 ꢀC after 30 min MW irradiation.
Instead of MW, comparative reactions were carried out in a 50 mL three-necked flask
with a reflux condenser and a thermometer in an oil bath. Other reaction conditions
were kept as identical as those indicated in Entry 3 (Table 1). The mixture was refluxed
at boiling temperature and held for 5 h under vigorous stirring. An isolated yield of
butane-1,4-diyl dibenzoate of 90% was obtained. Obviously, the MW irradiation dra-
matically shortened the reaction time from 5 h to 30 min.
As it stands, the solubility of organic substrates in water could be enhanced with
the aid of a PTC. Quaternary ammonium salts such as tetrabutylammonium chlor-
ide (TBAC), tetrabutylammonium bromide (TBAB), trimethylbenzylammonium
chloride (TMBAC), hexadecyltrimethylammonium bromide (HDTMA), and poly-
ethylene glycol (PEG-400) were applied herein as PTCs in the diesterification of
potassium benzoate with 1,4-dibromomethane. The effect of PTCs on the reaction
is listed in Table 2. The reaction proceeded very slowly or not at all in the
absence of PTC.[26]
Table 2 indicates that quaternary ammonium salts are much better than PEGs. It
may be attributed to the easy hydrolyzation of PEGs under alkaline conditions. Among
the quaternary ammonium salts, TBAB gave the higher yield. Aromatic carboxylates can
easily be combined with quaternary ammonium salts. Otherwise, bromide anion of
TBAB is a better leaving group, compared with chloride anion of TBAC.

4
S. DING ET AL.
Table 2. Optimization of PTC of the diesterification of potassium benzoate with 1,4-dibromobutanea.
O
O
O
K2CO3, PTC
H2O, MW
Br(CH2)4Br + 2
C6H5
O-K+
C6H5
O
4
O
C6H5
PTC
Yield ( %)b
TBAC
90
TBAB
92
TMBAC
25
HDTMA
None
PEG-400
31
aReaction conditions: potassium benzoate (5 mmol), 1,4-dibromobutane (2.5 mmol), K2CO3 (1 mmol), PTC (1 mmol), water
(1 mL). MW irradiation at 100 ꢀC for 30 min on 10 W.
bAverage isolated yield from twice reaction.
Table 3. Substrate scope of aromatic carboxylates in the diesterificationa.
O
O
O
TBAB, K CO , H2O
2
3
Br(CH ) Br +
2 4
2
MW, 100° C
Ar
O-
Ar
4
O
O
Ar
1
2a-k
3a-k
O
O
O
O
O
O
Br
Br
O
O
O
O
4
4
O
O
4
Br
Br
3a (92%)b
3b (84%)
3c (83%)
O
O
O
O
O
I
O
I
O
O
O
O
4
O
O
4
4
NO
CH
3
O N
H C
3
2
2
3d (82%)
3e (82%)
3f (93%)
O
O
O
O
O
O
O
O
O
O
4
O
O
4
O
O
4
3g (94%)
3h (90%)
3i (95%)
O
O
O
O
O
O
4
O
O
4
j (89%)
3k (88%)
aReaction conditions: potassium benzoate (5 mmol), 1,4-dibromobutane (2.5 mmol), K2CO3 (1 mmol), TBAB (1 mmol),
water (1 mL). MW irradiation at 100 ꢀC for 30 min on 10 W.
bNumbers in parentheses are the average isolated yields from twice reactions.
Various aromatic carboxylates, including heteroaromatic acids, reacted well with 1,4-
dibromobutane under the reaction conditions optimized above (Tables 1 and 2) in
high yield.
A wide array of aromatic carboxylates could be efficiently diesterifisized in high yield,
no matter which substitute bears on the aromatic ring, either an electron-withdrawing
group or an electron-donating group. It is worth pointing out that (2E)-butane-1,4-diyl
bis (3-phenylacrylate) (3k) is a trans-isomer (Table 3), which was identified by 1H
NMR and melting point. In all cases examined, the diesterification reactions were clean,

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5
essentially forming pure diesters in a short reaction time. The products were simply iso-
lated by filtration.
Experimental
General methods
All commercially available reagents were used without further purification. Column
chromatography was performed on silica gel (200–400 mesh). Melting points were
1
determined on a WRS-1A digital instrument and uncorrected. H (400 MHz) and 13C
(100 MHz) NMR spectra were recorded on a JNM-ECS400M spectrometer in CDCl3
with TMS as an internal standard at room temperature, unless otherwise indicated.
EI–MS data were measured with a TRACE DSQ GC–MS spectrometer. Elemental
analysis (% C, H, N) was performed by Vario EL analyzer. Microwave reactions were
conducted in a CEM Focused MW Synthesis System (CEM Corp., Matthews, NC). All
substrates and reagents were obtained from commercial sources and 1, 4-dibromobu-
tane was used as received.
General experimental procedures
In a 10-mL glass tube, (potassium) aromatic carboxylate (5.0 mmol), 1,4-dibromobutane
(2.5 mmol), K2CO3 (1.0 mmol), TBAB (1.0 mmol), 1 mL H2O, and a magnetic stir bar
were placed. The vessel was sealed with a septum and placed into the MW cavity.
Microwave irradiation of 10 W was used, with the temperature was ramped from room
temperature to 100 ꢀC. Once 100 ꢀC was reached, the reaction mixture was held at this
temperature for 30 min. After cooling the mixture to room temperature, the reaction
vessel was opened and the contents poured into a beaker with 50 mL water. The prod-
uct was washed fully and filtered under vacuum. The product was recrystallized from
95% ethanol or purified by column chromatography on silica gel using petroleum-ethyl
acetate (3:1 v/v) as the eluent, giving analytically pure products.
Butane-1,4-diyl dibenzoate (3a)
1
White crystal, mp (ꢀC) 82–83. H NMR (400 MHz, CDCl3): d ¼ 1.90–2.00 (m, 4H), 4.40
(m, 4H), 7.25–7.50 (m, 4H), 7.52–7.57 (m, 2H), 8.03–8.06 (m, 4H). 13C NMR
(100 MHz, CDCl3): d ¼ 25.5, 64.4, 128.3, 129.5, 130.2, 132.8, 166.5. MS (m/z): Calculated
for C18H18O4: 298.12, Found: 298. Anal. Calcd. For C18H18O4: C, 72.47; H, 6.08; Found:
C, 72.46; H, 6.05;
Conclusions
In this work, we present a simple, highly efficient protocol for the synthesis of butame-
thylenediesters in water. The diesterification reactions proceeded under focused MW
irradiation in combination with PTCs, which constitutes a novel and powerful
approach. Its valuable features are atom-efficiency, short reaction time, broad substrate

6
S. DING ET AL.
cope, and environment protection. From a synthetic perspective, these results explore
new possibilities of applying this entry to preparing diesters in water.
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