C–O bond formation via oxidative-coupling pathway in eutectic mixture of choline chloride/urea as a green solvent

Article abstract of DOI:10.1016/j.molliq.2018.12.046

C–O bond formation between terminal alkenes/benzyl alcohols as an arylcarboxy surrogate and carbonyl compounds in a biodegradable deep eutectic solvent (DES) based on choline chloride and urea was performed. By employment of TBAI as catalyst and TBHP as oxidant, various derivatives of carbonyl compounds were benzylated in α position in good to high yield at 90 °C. Moreover, α-oxybenzoylation of diethyl malonate with carboxylic acids was performed in the above-mentioned DES by employment of NaI as the catalyst and TBHP as the oxidant at 60 °C.

Full text of DOI:10.1016/j.molliq.2018.12.046

Accepted Manuscript
C-O bond formation via oxidative-coupling pathway in eutectic
mixture of choline chloride/urea as a green solvent
Dariush Saberi, Neda Manouchehri, Khodabakhsh Niknam
PII:
S0167-7322(18)34344-7
DOI:
Reference:
https://doi.org/10.1016/j.molliq.2018.12.046
MOLLIQ 10122
To appear in:
Journal of Molecular Liquids
Received date:
Revised date:
Accepted date:
22 August 2018
13 November 2018
7 December 2018
Please cite this article as: Dariush Saberi, Neda Manouchehri, Khodabakhsh Niknam , C-
O bond formation via oxidative-coupling pathway in eutectic mixture of choline chloride/
urea as a green solvent. Molliq (2018), https://doi.org/10.1016/j.molliq.2018.12.046
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ACCEPTED MANUSCRIPT
C-O bond formation via oxidative-coupling pathway in eutectic mixture of choline
chloride/urea as a green solvent
Dariush Saberi,*[a] Neda Manouchehri,[b] and Khodabakhsh Niknam*[b]
[a]Fisheries and Aquaculture Department, College of Agriculture and Natural Resources, Persian Gulf
University, Bushehr 75169, Iran. E. mail: saberi_d@pgu.ac.ir
[b]Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
niknam@pgu.ac.ir; khniknam@gmail.com
Abstract: C-O bond formation between terminal alkenes/benzyl alcohols as an arylcarboxy
surrogate and carbonyl compounds in a biodegradable deep eutectic solvent (DES) based on
choline chloride and urea was performed. By employment of TBAI as catalyst and TBHP as
oxidant, various derivatives of carbonyl compounds were benzylated in  position in good to
high yield at 90 °C. Moreover, -oxybenzoylation of diethyl malonate with carboxylic acids
were performed in the above-mentioned DES by employment of NaI as the catalyst and
TBHP as the oxidant at 60 °C.
Keywords: Deep eutectic solvent, Choline chloride, Oxidative-coupling, -Oxybenzoylation,
Green solvent
Introducton
Most of chemical reactions are carried out in solvents, so solvent selection is an important
factor in the design of chemical reactions in view of green chemistry. Since ionic liquids
(ILs) have emerged, many of organic reactions proceeded in organic solvents were directed
toward ILs due to their unique properties such as excellent chemical and thermal stability,
non-volatility, non-coordinating nature, good solvating capability, wide liquid range, and ease
of recycling [1]. However, ILs suffered some drawbacks too, such as difficulty in
preparation, high cost and toxicity which hampered their utilization.
Recently, deep eutectic solvents (DESs) have emerged. Structurally, DESs are similar to
ionic liquids (ILs) due to the fact that the both have low vapor pressure and low flammability

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[2]. Contrary to ILs, DESs are biodegradable, non-toxic, and inexpensive. Another advantage
of DESs is that they are easily prepared by combining two components, a hydrogen acceptor
(mainly choline chloride) and a hydrogen donor. The most famous component of this family
is the combination of choline chloride and urea (ChCl/Urea) which are very cheap and non-
toxic compounds. Since their emergence in 2003, ChCl/Urea plays an important role in
organic reactions as catalysts as well as solvents [3].
α-Acyloxyketones, formed via the α-acyloxylation of carbonyl compounds, are useful
building blocks [4] and can facilely transform into α-hydroxyketones as a structural subunit
in a variety of biologically active natural products [5]. Moreover, the α-functionalization of β-
dicarbonyl compounds with heteroatomic groups, in particular α-oxygen, is one of the most
promising transformations, as it provides key intermediates for the synthesis of a variety of
heterocyclic and natural products that adopt unique interests in medicinal chemistry [6].
To date, various methods have been proposed for the synthesis of α-acyloxyketones including
substitution reaction of α-halo carbonyl compounds [7] or the oxidative coupling of carbonyl
compounds with heavy metal oxidants [8], copper-catalyzed insertion of α-diazo ketones into
carboxylic acids [9], α-acyloxylation of ketones by using N-methyl-O benzoylhydroxylamine
[10], iodobenzene-catalyzed α-acetoxylation of ketones by using m-chloroperbenzoic acid
[11], (hypo)iodite-catalyzed direct α-acyloxylation of carbonyl compounds with carboxylic
acids [12], and α-acyloxylation of ketones with benzylic alcohols or aryl alkenes in the
presence of a TBAI/TBHP system [13]. Most of these methods have used organic solvents
such as toluene, benzonitrile, ethylacetate, DMSO, 1,4-dioxane and so on. Here, we are going
to report the -oxyacylation of carbonyl compounds with aryl alkenes/benzyl alcohols and -
oxybenzoylation of diethyl malonate with carboxylic acids using DES as a green reaction
media.
Result and discussion

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To investigate the effective reaction parameters such as temperature, catalyst and oxidant,
styrene and propiophenone were chosen as the model substrates. The results are summarized
in Table 1. In the first attempt, the corresponding product 4a was obtained in 45% yield under
the following conditions; styrene (0.5 mmol), propiophenone (1 mmol), ChCl/Urea (2 mL),
TBAI (10 mol%) as catalyst and TBHP (3 equiv) as oxidant at 80 °C (Table 1, entry 1). By
doubling the catalyst, efficiency increased up to 55%, whereas we faced reduction in
efficiency by further increase to 30 mol% (Table 1, entries 2 and 3). The yield reached to
65% when 7 equivalent of oxidant was used. Further increase in oxidation did not have an
effect on the yield of the product )Table 1, entries 4-6). The temperature proved its
effectiveness in this reaction. At 90 °C, maximum efficiency is achieved. The efficiency
dropped sharply by the increase in temperature to 130 °C. At 60 °C, the reaction was
completely stopped (Table 1, entries 7-10). No product formation under catalyst-free
condition as well as the decrease in yield in the presence of I2, KI, NaI or TBAB showed that
the TBAI plays a crucial role for this transformation (Table 1, entries 11-15). Moreover,
TBHP played a key role in this reaction since in its absence no product was formed (Table 1,
entry 16). For unknown reasons, the yield of the product in ChCl:ethylene glycol DES was
lower than ChCl:urea (Table 1, entry 17). The replacement of styrene with benzyl alcohol
leads to a similar product. However, in the oxidative-coupling reaction of benzyl alcohol with
propiophenone, the product 4a was obtained in 68% yield (Table 1, entry 18).
Scope of the reaction was investigated by employment of various styrene/benzyl alcohol
derivatives as well as ketone moiety under the optimized reaction condition as follow: TBAI
(20 mol%), TBHP (7 eq), ChCl:urea (2 mL), at 90 °C. The structures of alcohols/styrenes and
ketones used in this reaction are shown in Figure 1.
Various derivatives of styrene and benzyl alcohol reacted with propiophenone and were
converted to the corresponding product in moderate yields. The type of substitution on the

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aromatic ring did not significantly affect the efficiency of the reaction. Unfortunately, the
reaction between styrene (or 4-chlorostyrene) and cyclohexanone was not satisfactory and the
corresponding products 4k and 4l were obtained in low yields. Instead, the reaction of benzyl
alcohol with cyclohexanone was better and the product 4k was achieved with 45% yield. 4-
Table 1: Screening the reaction conditions1
Entry
1
Solvent
Urea-ChCl
Temp.(°C)
80
Catalyst (mol %)
TBAI (10)
TBHP
3eq
Yield (%)b
45
2
3
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
80
80
80
80
80
90
100
130
60
90
90
90
90
90
90
90
TBAI (20)
TBAI (30)
TBAI (20)
TBAI (20)
TBAI (20)
TBAI (20)
TBAI (20)
TBAI (20)
TBAI (20)
-
3eq
3eq
5eq
7eq
8eq
7eq
7eq
7eq
7eq
7eq
7eq
7eq
7eq
7eq
-
55
45
50
65
65
70
70
20
4
5
6
7
8
9
10
11
12
13
14
15
16
17
-
-
I2 (20)
30
30
20
-
KI (20)
NaI (20)
TBAB (10)
TBAI (20)
TBAI (20)
-
Ethylene glycol -
ChCl
7eq
60
18
Urea-ChCl
90
TBAI (20)
7eq
68c
aReaction conditions: 1a (0.5 mmol), 3a (1 mmol), DES (2 mL), 24 h, under air atmosphere.
bIsolated yield. cBenzyl alcohol was used instead of styrene.
methoxy benzyl alcohol in the reaction with cyclohexanone has a better performance and
product 4n was isolated in 65% efficiency. The ketones such as 4-phenyl cyclohexanone, 4-
(tert-butyl)cyclohexanone and cyclopentanone were also subjected to the reaction conditions

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and converted to the corresponding products in reaction with 4-methoxy benzyl alcohol
(products 4o, 4p, 4q). The structures of the synthesized products are shown in Table 2.
Figure 1: Diversity of styrene (1a-1e), benzyl alcohol (2a-2f), and ketone (3a-3e)
derivatives.
From a mechanistic point of view and based on the previously reported works, it is expected
that this reaction will proceed via a radical pathway. To prove this, when the model reaction
was performed in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), a well
known radical scavenger, product efficiency of 4a decreased to 40%. This result showed that
the route to the product could be radical. On the other hand, when benzoic acid, instead of
styrene, was subjected to the reaction conditions, product 4a was achieved with 70% yield
after 16 h of the reaction time. Therefore, benzoic acid can be an intermediate in this reaction.
Based on these observations and previously reported works [14], a mechanism shown in

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Table 2: Scope of the reactiona
aReaction conditions: 1 or 2 (0.5 mmol), 3 (1 mmol), DES (2 mL), TBAI (20 mol%), TBHP
(7 equiv), 90 °C, 24 h, under air atmosphere. The yields refer to the isolated pure products.

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Scheme 2 is proposed for this transformation. Styrene (1a) in the presence of TBAI/TBHP is
converted to benzoic acid (I) via the intermediacy of phenylglyoxal and benzaldehyde [15].
Then, tert-butoxyl radical abstract a hydrogen atom from the propiophenone (3a) to generate
the radical II [16] which converted to the carbocation III in the presence of I2. Carbocation
III can be transformed to the product 4a via nucleophilic attack by benzoate anione I.

Scheme 2: Proposed mechanism

-acyloxylation of diethyl malonate with carboxylic acids was also studied in DES. The
studies performed to achieve an optimal condition are shown in Table 3. In the reaction
between benzoic acid and diethyl malonate with a stoichiometric ratio of 1 to 2, under the
following conditions; NaI as the catalyst (10 mol%), TBHP as the oxidant (1 equiv) and
Urea/ChCl as the solvent (2 mL) at 70 °C, product 7a was obtained with maximum
efficiency. The deviation from these conditions, by changing the catalyst and temperature,
did not have a better result. Worthy of note is that, with increasing temperature to 110 °C,
product 8, resulting from the oxidative self-coupling of diethyl malonate, was dominant and
isolated in 60% yield (Table 3, entry 11). Meanwhile, an increase in the amount of diethyl
malonate also leads to the formation of product 8 (Table 3, entries 16). In the absence of a

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catalyst and oxidant, or even in the presence of TBAB, the desired product is not formed at
all (Table 3, entries 5, 13, 14). This shows that NaI and TBHP are two crucial elements for
this coupling reaction.
Table 3: Screening the reaction conditions1
Entry
1
Solvent
Urea-ChCl
Temp.(°C)
60
Catalyst (mol %)
TBAI (10)
TBHP
1eq
Yield (%)b
60
2
3
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
Urea-ChCl
60
60
60
60
60
60
40
R.T
90
110
60
60
60
60
60
I2 (10)
NaI (10)
KI (10)
TBAB (10)
NaI (20)
NaI (5)
1eq
1eq
1eq
1eq
1eq
1eq
1eq
1eq
1eq
1eq
2eq
1eq
-
55
70
60
-
4
5
6
70
50
55
<10
7
8
NaI (10)
NaI (10)
NaI (10)
NaI (10)
NaI (10)
-
9
10
11
12
13
14
15
16
50
15c
55
-
NaI (10)
NaI (10)
NaI (10)
-
1eq
70
60d,e
1eq
aReaction conditions: 5a (1 equiv), 6 (2 equiv), DES (2 mL), 8 h, under air atmosphere.
c
d
e
bIsolated yield. product 8 was isolated in 60% yield. 3 equiv. of 6 was used. Compound 8
was formed in 20% yield.
Subsequently, to prove the universality of the method, several benzoic acid derivatives
including electron-donating and electron-withdrawing groups were converted to the

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corresponding products under optimized conditions. The stractures of the synthesized
compounds are shown in Table 4. All the products were obtained in acceptabe yields.
Table 4: α-Oxybenzoylation of diethyl malonatea
aReaction conditions: 5 (1 equiv), 6 (2 equiv), DES (2 mL), in the air. The yields refer to the
isolated pure products.
On the basis of previous work in the literature [17] and our own results described above, we
proposed a plausible mechanism for the present reactions, which is shown in Scheme 3.
Iodide was initially oxidized by TBHP to Na[IO]−,which was further oxidized to a key
intermediate hypoiodite Na[IO2]− (A) with one more equivalent of TBHP [18]. The oxidative
addition of 6 at the α-position by A would give a key β-diester intermediate B, which readily
experienced substitution by 5a to give the α-oxybenzoylation product 7a under mild

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conditions, releasing the catalyst precursor Na[IO]−. In the presence of excess 6, intermediate
B converted to the product 8.
Scheme 3: Proposed mechanism
The possibility of recycling the catalyst and ChCl:Urea was examined for the synthesis of
product 4a under the optimized conditions. The recycling process was very simple, and thus
after each run, the water (10 mL) added to the reaction mixture and then the organic
compound extracted with ethyl acetate (2 × 10 mL). The aqueous phase including DES and
TBAI was concentrated, charged with fresh reagents and subjected to the next run. The
process was followed for five successive cycles and only a slight decrease in the product
efficiency was observed after the fourth cycle (Table 5).

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Table 5 Recycling of deep eutectic solvent and TBAI for the formation of product 4aa
Entry
Cycle
% Yield
1.
2.
3.
4.
Fresh
70
67
65
65
1st recycle
2nd recycle
3rd recycle
aReaction conditions: same to optimized conditions of the model reaction
In Table 6, the efficiency of our catalytic system has been compared with some
previously reported procedures in the synthesis of product 4a
Table 6: Comparing our catalytic pathway performance with some which previously reported
Entry
reagents
1a + 3a
5a + 3a
9 + 3a
Conditions
% Yield
65
Ref.
[14]
1
2
3
4
5
6
TBAI, TBHP, 80 °C, PhCN, 24 h
TBAI, TBHP, 70 °C, EtOAc, 24 h
DMSO, 50 °C, 48 h
99
[12]
69
[10a]
2a + 3a
1a + 3a
2a + 3a
TBAI, TBHP, 90 °C, PhCN, 24 h
TBAI, TBHP, 90 °C, ChCl:Urea, 24 h
TBAI, TBHP, 90 °C, ChCl:Urea, 24 h
84
[13]
70
This work
This work
68
As can be seen in Table 6, our catalytic system is comparable with other in terms of
reaction conditions and yields. Nevertheless, low price, eco-friendly, and reusability of
DES can be the advantage toward the others.
Conclusion
In summary, we have successfully synthesized a variety of -acyloxyl-carbonyl compounds
via an intermolecular C-O bond formation of terminal alkenes/benzyl alcohols as an

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arylcarboxy surrogate and carbonyl compounds and diethyl malonate with carboxylic acids
mediated by iodide in DES. The combination of choline chloride and urea (ChCl/Urea) was
used as a very cheap, non-toxic and reusable solvent in these transformations. Various
derivatives of starting materials were subjected to the reaction conditions and converted to
the corresponding products in good yields.
Experimental section
General Information
All reagents were purchased from commercial suppliers and used without further purification.
All experiments were carried out under air atmosphere. Column chromatography was carried
out with Merck silica gel 60 (63-200 mesh). Analytical TLC was performed with Merck
1
13
silica gel 60 F254 plates, and the products were visualized by H NMR and C NMR (300
MHz and 75 MHz, respectively) spectra were recorded in CDCl3. Chemical shifts (δ) are
reported in ppm using TMS as internal standard, and spin-spin coupling constants (J) are
given in Hz. IR spectra were recorded on a Perkin-Elmer FT/IR 1760 as KBr pellets.
General procedure for the synthesis of compounds 4 (4a as an example):
A mixture of styrene (0.5 mmol), propiophenone (1 mmol), Bu4NI (36.9 mg, 20 mol%), in
ChCl/Urea (2 mL) was placed in the two-necked round bottomed flask fitted with a
condenser under an air atmosphere at room temperature. Then, TBHP (70% aqueous solution,
480 μL, 3.5 mmol) was added to the reaction mixture slowly over a 5 min period, and the
mixture was placed in an oil bath with magnetic stirring at 90 °C. After completion (24 h),
the reaction mixture was cooled to room temperature, the water (10 mL) added to it and then
the organic compound extracted with ethyl acetate (2 × 10 mL). The combined ethyl acetate
layers were washed successively with a saturated solution of sodium thiosulfate (2 × 10 mL),
dried with anhydrous Na2SO4, and filtered. The solvent was evaporated under reduced

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pressure to give the crude mixture, which was purified by column chromatography on silica
gel (60–120/100–200 mesh size, n-hexane/ethyl acetate) to afford the desired product 4a.
General procedure for the synthesis of compounds 7 (7a as an example):
A mixture of benzoic acid (0.3 mmol), diethyl malonate (0.6 mmol), NaI (4 mg, 10 mol%), in
ChCl/Urea (2 mL) was placed in the two-necked round bottomed flask fitted with a
condenser under an air atmosphere at room temperature. Then, TBHP (70% aqueous solution,
1 equiv) was added to the reaction mixture, and the mixture was placed in an oil bath with
magnetic stirring at 60 °C. After completion (8 h), the reaction mixture was cooled to room
temperature, the water (10 mL) added to it and then the organic compound extracted with
ethyl acetate (2 × 10 mL). The combined ethyl acetate layers were washed successively with
a saturated solution of sodium thiosulfate (2 × 10 mL), dried with anhydrous Na2SO4, and
filtered. The solvent was evaporated under reduced pressure to give the crude mixture, which
was purified by column chromatography on silica gel (60–120/100–200 mesh size, n-
hexane/ethyl acetate) to afford the desired product 7a.
Analytical data of some selected compounds
1-Oxo-1-phenylpropan-2-yl benzoate (4a): Following the general procedure, the product
4a was obtained as white solid in 70% (0.089 gr) yield after column chromatography; M. p.
92-94 ºC; 1H NMR (300 MHz, CDCl3): δ 1.71 (d, J = 7.2 Hz, 3H), 6.25 (q, J = 7.2 Hz, CH),
7.46–7.54 (m, 4H, Ar), 7.59–7.65 (m, 2H, Ar), 8.03–8.05 (m, 2H, Ar), 8.12–8.14 (m, 2H,
13
Ar); C NMR (CDCl3, 75 MHz): δ 17.2, 71.9, 128.4, 128.6, 128.9, 129.5, 129.9, 133.3,
133.6, 134.5, 166.0, and 196.8. IR (KBr, cm-1): ν 2984, 2931, 1731, and 1621.

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1-Oxo-1-phenylpropan-2-yl 2-chlorobenzoate (4d): Following the general procedure,
the product 4d was obtained as white solid in 68% (0.098 gr) yield after column
1
chromatography; M. p. 45 ºC; H NMR (300 MHz, CDCl3): δ 1.7 (d, J = 9.6 Hz, 3H), 6.22
(q, J = 9.2 Hz, CH), 7.44–7.48 (m, 2H, Ar), 7.49–7.55 (m, 2H, Ar), 7.60–7.66 (m, 1H, Ar),
8.01–8.15 (m, 4H, Ar); 13C NMR (CDCl3, 75 MHz): δ 17.2, 72.1, 128.0, 128.5, 128.8, 128.9,
129.9, 131.3, 133.7, 134.4, 165.1, and 196.5; MS (EI, 70 eV): m/z (%) = 288 (M+, 5), 244
(23), 210 (33), 139 (100), 105 (100), 77 (100), 51 (74).
1-Oxo-1-phenylpropan-2-yl 4-(tert-butyl)benzoate (4f): Following the general
procedure, the product 4f was obtained as yellow liquid in 60% (0.093gr) yield after column
1
chromatography. H NMR (300 MHz, CDCl3): δ 1.2 (s, 9H, 3 × CH3), 1.58 (d, J = 6.8 Hz,
13
3H), 6.12 (q, J = 6.8 Hz, CH), 7.18–7.52 (m, 5H, Ar), 7.91–7.95 (m, 4H, Ar); C NMR
(CDCl3, 75 MHz): δ 17.1, 31.1, 35.1, 71.6, 125.4, 126.7, 128.5, 128.7, 129.7, 133.5, 134.5,
157.5, 166, and 195.8.
1-Oxo-1-phenylpropan-2-yl 4-bromobenzoate (4i): Following the general procedure,
the product 4i was obtained as white solid in 60% (0.06 gr) yield after column
chromatography; M. p. 93-96 ºC; 1H NMR (300 MHz, CDCl3): δ 1.5 (d, J = 9.6 Hz, 3H), 6.11
(q, J = 9.6 Hz, CH), 7.32–7.41 (m, 2H, Ar), 7.45–7.50 (m, 3H, Ar), 7.91 (d, J = 9.6 Hz, 2H,
13
Ar), 8.0 (d, J = 9.6 Hz, 2H, Ar); C NMR (CDCl3, 75 MHz): δ 17.2, 71.9, 128.4, 128.5,
128.6, 128.9, 131.8, 133.3, 133.6, 134.5, 166.0, and 196.5; MS (EI, 70 eV): m/z (%) = 334
(M+, 17), 288 (100), 239 (49), 227 (53).
2-Oxocyclohexyl 4-methoxybenzoate (4m): Following the general procedure, the
product 4m was obtained as yellow liquid in 65% (0.08 gr) yield after column
chromatography. 1H NMR (300 MHz, CDCl3): δ 1.24-1.36(m, 8H, 4 × CH2), 2.0-2.2 (m, 1H,
13
CH), 3.79 (s, 3H, OCH3), 6.85 (d, J = 11.6 Hz,, 2H, Ar), 7.83 (d, 2H, J = 12 Hz, Ar); C

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NMR (CDCl3, 75 MHz): δ 26.1, 26.2, 28.1, 30.9, 55.4, 83.8, 113.9, 119.8, 131.2, 132.2,
163.6, 164.2; MS (EI, 70 eV): m/z (%) = 248 (M+, 2), 135 (85), 77 (60), 43 (100).
2-Oxocyclopentyl 4-methoxybenzoate (4q): Following the general procedure, the
product 4q was obtained as white solid in 65% (0.076 gr) yield after column
1
chromatography; M. p. 180-185 ºC; H NMR (300 MHz, CDCl3): δ 0.91-0.95 (m, 2H, CH2),
1.28-1.36 (m, 4H, 2 × CH2), 3.91 (s, 3H, OCH3), 6.97 (d, J = 8.8 Hz,, 2H, Ar), 7.29 (s, 2H,
13
CH2), 8.08 (d, 2H, J = 7.2 Hz, Ar); C NMR (CDCl3, 75 MHz): δ 10.9, 28.8, 29.7, 55.5,
75.1, 113.7, 121.6, 132.4, 164, 171.6, and 212.5.
Diethyl 2-(benzoyloxy)malonate (7a): Following the general procedure, the product 7a
was obtained as yellow liquid in 70% (0.065gr) yield after column chromatography. 1H NMR
(300 MHz, CDCl3): δ 1.36 (t, J = 7.2 Hz, 6H, 2 × CH3), 4.29-4.42 (m, 4H, 2 × CH2), 5.78 (s,
CH), 7.49–7.52 (m, 2H, Ar), 7.63–7.66 (m, 1H, Ar), 8.16–8.18 (m, 2H, Ar); 13C NMR
(CDCl3, 75 MHz): δ 14.0, 62.6, 72.1, 128.5, 130.3, 133.8, 164.6, and 165.2; MS (EI, 70 eV):
m/z (%) = 280 (M+, 3), 115 (43), 105 (100), 77 (55), 43 (23).
Diethyl 2-((2-bromobenzoyl)oxy)malonate (7b): Following the general procedure, the
product 7b was obtained as yellow liquid in 68% (0.081gr) yield after column
chromatography. 1H NMR (300 MHz, CDCl3): δ 1.26 (t, J = 7.2 Hz, 6H, 2 × CH3), 4.24-4.28
(m, 4H, 2 × CH2), 5.69 (s, CH), 7.31–7.34 (m, 2H, Ar), 7.61–7.64 (m, 1H, Ar), 7.95–7.98 (m,
1H, Ar).
Diethyl 2-((4-chlorobenzoyl)oxy)malonate (7c): Following the general procedure, the
product 7c was obtained as yellow liquid in 70% (0.073gr) yield after column
1
chromatography. H NMR (300 MHz, CDCl3): δ 1.23-1.28 (m, 6H, 2 × CH3), 4.22-4.29 (m,
13
4H, 2 × CH2), 5.66 (s, CH), 7.37 (d, 2H, J = 11.6 Hz, Ar), 8.0 (d, 2H, J = 11.6 Hz, Ar); C
NMR (CDCl3, 75 MHz): δ 14.0, 62.6, 72.2, 126.9, 128.9, 131.5, 140.4, 164.30, and 165.36;
MS (EI, 70 eV): m/z (%) = 314 (M+, 90), 295 (15), 269 (73), 243 (38).

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Diethyl 2-((4-methylbenzoyl)oxy)malonate (7e(: Following the general procedure, the
product 7e was obtained as yellow liquid in 70% (0.068gr) yield after column
1
chromatography. H NMR (300 MHz, CDCl3): δ 1.35 (t, J = 7.2 Hz, 6H, 2 × CH3), 2.45 (s,
CH3), 4.32-4.37 (m, 4H, 2 × CH2), 5.77 (s, CH), 7.29 (d, 2H, J = 7.2 Hz, Ar), 8.05 (d, 2H, J =
7.2 Hz, Ar); 13C NMR (CDCl3, 75 MHz): δ 14.0, 21.8, 62.5, 72.1, 125.7, 129.2, 130.2, 144.7,
164.7, and 165.2. IR (KBr, cm-1): ν 2979, 2933, 1722, and 1690; MS (EI, 70 eV): m/z (%) =
294 (M+, 20), 119 (100), 91 (85), 65 (45), 43 (25).
Diethyl 2-((2-naphthoyl)oxy)malonate (7g): Following the general procedure, the
product 7g was obtained as yellow liquid in 68% (0.067gr) yield after column
1
chromatography. H NMR (300 MHz, CDCl3): δ 1.26-1.29 (m, 3H, CH3), 1.36-1.39 (m, 3H,
CH3), 4.35-4.43 (m, 4H, 2 × CH2), 5.87 (s, 1H, CH), 7.54–7.60 (m, 2H, Ar), 7.61–7.65 (m,
1H, Ar), 7.89–7.94 (m, 2H, Ar), 8.00 (d, 1H, J = 8.0 Hz, Ar), 8.15 (d, 1H, J = 8.8 Hz, Ar),
13
8.76 (s, 1H, Ar); C NMR (CDCl3, 75 MHz): δ 14.1, 14.2, 62.6, 72.3, 125.3, 125.7, 126.8,
127.8, 128.4, 128.7, 129.5, 132.1, 132.4, 135.9, 164.6, 165.3, and 167.8.
Diethyl 2-((1-naphthoyl)oxy)malonate (7h): Following the general procedure, the
product 7h was obtained as yellow liquid in 60% (0.059gr) yield after column
chromatography. 1H NMR (300 MHz, CDCl3): δ 1.38 (t, J = 9.2 Hz, 6H, 2 × CH3), 4.34-4.45
(m, 4H, 2 × CH2), 5.91 (s, CH), 7.54–7.61 (m, 2H, Ar), 7.64–7.69 (m, 1H, Ar), 7.91–7.94 (m,
1H, Ar), 8.09–8.12 (m, 1H, Ar), 8.45 (dd, 1H, J1 = 9.6, J2 = 1.6 Hz, Ar), 8.97–9.00 (m, 1H,
Ar); 13C NMR (CDCl3, 75 MHz): δ 14.1, 62.7, 72.3, 124.6, 125.1, 125.6, 126.4, 128.2, 128.6,
131.4, 131.5, 133.8, 134.4, 164.7, and 165.8; MS (EI, 70 eV): m/z (%) = 330 (M+, 20), 155
(100), 127 (70), 105 (21), 77 (21), 43 (22).
Diethyl 2-((3-(nitrooxy)benzoyl)oxy)malonate (7i): Following the general procedure, the
product 7i was obtained as yellow liquid in 65% (0.07gr) yield after column chromatography.
1H NMR (300 MHz, CDCl3): δ 1.20-1.29 (m, 6H, 2 × CH3), 4.23-4.27 (m, 4H, 2 × CH2), 5.71

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13
(s, CH), 7.63 (t, 1H, J = 8 Hz, Ar), 8.38–8.41 (m, 2H, Ar), 8.8 (s, 1H , Ar); C NMR
(CDCl3, 75 MHz): δ 13.8, 62.5, 72.5, 125.1, 128.2, 129.8, 135.3, 135.7, 148.3, 162.3, 163.9.
1
Tetraethyl ethene-1,1,2,2-tetracarboxylate (8(: H NMR (300 MHz, CDCl3): δ 1.25-
1.33 (m, 12H, 4× CH2), 4.12–4.34 (m, 8H); 13C NMR (CDCl3, 75 MHz): δ 13.8, 62.5, 135.3
and 162.3.
Acknowledgements
We are thankful to Persian Gulf University Research Council for partial support of this
work.
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Graphical abstract
C-O bond formation via oxidative-coupling pathway in eutectic mixture of choline
chloride/urea as a green solvent
Dariush Saberi,* Neda Manouchehri, and Khodabakhsh Niknam*

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Highlights:
 Use the choline chloride/ urea as a biodegradable and green solvent in oxidative-coupling
reactions
 C-O bond formation under transition metal-free conditions
 Employment of TBHP as a green oxidant
 Synthesis of -acyloxyl-carbonyl compounds in acceptable yields