urea as a green solvent

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: DOI: Reference:

S0167-7322(18)34344-7 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 , CO 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: [email protected] [b] Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran

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[email protected]; [email protected]

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Abstract: C-O bond formation between terminal alkenes/benzyl alcohols as an arylcarboxy

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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

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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

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were performed in the above-mentioned DES by employment of NaI as the catalyst and TBHP as the oxidant at 60 °C.

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Keywords: Deep eutectic solvent, Choline chloride, Oxidative-coupling, -Oxybenzoylation, Green solvent Introducton

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Most of chemical reactions are carried out in solvents, so solvent selection is an important

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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

ACCEPTED MANUSCRIPT [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 nontoxic compounds. Since their emergence in 2003, ChCl/Urea plays an important role in

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organic reactions as catalysts as well as solvents [3].

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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

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in a variety of biologically active natural products [5]. Moreover, the α-functionalization of β-

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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

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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

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substitution reaction of α-halo carbonyl compounds [7] or the oxidative coupling of carbonyl

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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

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[10], iodobenzene-catalyzed α-acetoxylation of ketones by using m-chloroperbenzoic acid [11], (hypo)iodite-catalyzed direct α-acyloxylation of carbonyl compounds with carboxylic

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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

ACCEPTED MANUSCRIPT 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

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doubling the catalyst, efficiency increased up to 55%, whereas we faced reduction in

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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

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effect on the yield of the product )Table 1, entries 4-6). The temperature proved its

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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

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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

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the TBAI plays a crucial role for this transformation (Table 1, entries 11-15). Moreover,

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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

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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

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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

ACCEPTED MANUSCRIPT 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-

Solvent Urea-ChCl

Temp.(°C) 80

Catalyst (mol %) TBAI (10)

TBHP 3eq

Yield (%)b 45

2

Urea-ChCl

80

TBAI (20)

3eq

55

3

Urea-ChCl

80

TBAI (30)

3eq

45

4

Urea-ChCl

80

TBAI (20)

5eq

50

5

Urea-ChCl

80

TBAI (20)

7eq

65

6

Urea-ChCl

80

TBAI (20)

8eq

65

7

Urea-ChCl

90

TBAI (20)

7eq

70

8

Urea-ChCl

100

TBAI (20)

7eq

70

9

Urea-ChCl

130

TBAI (20)

7eq

20

10

Urea-ChCl

60

TBAI (20)

7eq

11

Urea-ChCl

90

-

7eq

-

12

Urea-ChCl

90

I2 (20)

7eq

30

13

Urea-ChCl

90

KI (20)

7eq

30

14

Urea-ChCl

90

NaI (20)

7eq

20

15

Urea-ChCl

90

TBAB (10)

7eq

-

16

Urea-ChCl

90

TBAI (20)

-

-

Ethylene glycol ChCl Urea-ChCl

90

TBAI (20)

7eq

60

90

TBAI (20)

7eq

68c

18 a

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17

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Entry 1

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Table 1: Screening the reaction conditions1

Reaction conditions: 1a (0.5 mmol), 3a (1 mmol), DES (2 mL), 24 h, under air atmosphere. Isolated yield. cBenzyl alcohol was used instead of styrene.

b

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

ACCEPTED MANUSCRIPT and converted to the corresponding products in reaction with 4-methoxy benzyl alcohol

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(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)

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derivatives.

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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

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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

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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

a

Reaction 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.

ACCEPTED MANUSCRIPT 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

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III can be transformed to the product 4a via nucleophilic attack by benzoate anione I.

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Scheme 2: Proposed mechanism

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

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-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

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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

ACCEPTED MANUSCRIPT 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.

Yield (%)b 60

I2 (10)

1eq

55

NaI (10)

1eq

70

KI (10)

1eq

60

TBAB (10)

1eq

-

NaI (20)

1eq

70

60

NaI (5)

1eq

50

40

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NaI (10)

1eq

55

R.T

NaI (10)

1eq

<10

90

NaI (10)

1eq

110

NaI (10)

1eq

50 15c

Urea-ChCl

60

NaI (10)

2eq

55

13

Urea-ChCl

60

-

1eq

-

14

Urea-ChCl

60

NaI (10)

-

-

Urea-ChCl

60

NaI (10)

1eq

70

Urea-ChCl

60

NaI (10)

1eq

60d,e

Urea-ChCl

60

3

Urea-ChCl

60

4

Urea-ChCl

60

5

Urea-ChCl

60

6

Urea-ChCl

60

7

Urea-ChCl

8

Urea-ChCl

9

Urea-ChCl

10

Urea-ChCl

11

Urea-ChCl

12

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16

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2

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Temp.(°C) 60

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TBHP 1eq

Solvent Urea-ChCl

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Catalyst (mol %) TBAI (10)

Entry 1

15 a

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Table 3: Screening the reaction conditions1

Reaction conditions: 5a (1 equiv), 6 (2 equiv), DES (2 mL), 8 h, under air atmosphere.

b

Isolated yield. cproduct 8 was isolated in 60% yield. d3 equiv. of 6 was used. eCompound 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

ACCEPTED MANUSCRIPT corresponding products under optimized conditions. The stractures of the synthesized compounds are shown in Table 4. All the products were obtained in acceptabe yields.

a

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Table 4: α-Oxybenzoylation of diethyl malonatea

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Reaction 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

ACCEPTED MANUSCRIPT conditions, releasing the catalyst precursor Na[IO]−. In the presence of excess 6, intermediate

Scheme 3: Proposed mechanism

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B converted to the product 8.

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).

ACCEPTED MANUSCRIPT Table 5 Recycling of deep eutectic solvent and TBAI for the formation of product 4aa

Entry

Cycle

1. 2. 3. 4.

Fresh 1st recycle 2nd recycle 3rd recycle

% Yield

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70 67 65 65 a Reaction conditions: same to optimized conditions of the model reaction

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In Table 6, the efficiency of our catalytic system has been compared with some

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previously reported procedures in the synthesis of product 4a

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Table 6: Comparing our catalytic pathway performance with some which previously reported reagents

Conditions

% Yield

Ref.

1

1a + 3a

TBAI, TBHP, 80 °C, PhCN, 24 h

65

[14]

2

5a + 3a

TBAI, TBHP, 70 °C, EtOAc, 24 h

99

[12]

3

9 + 3a

DMSO, 50 °C, 48 h

69

[10a]

4

2a + 3a

TBAI, TBHP, 90 °C, PhCN, 24 h

84

[13]

5

1a + 3a

TBAI, TBHP, 90 °C, ChCl:Urea, 24 h

70

This work

6

2a + 3a

68

This work

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Entry

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TBAI, TBHP, 90 °C, ChCl:Urea, 24 h

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

ACCEPTED MANUSCRIPT 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

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the corresponding products in good yields.

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Experimental section

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General Information

All reagents were purchased from commercial suppliers and used without further purification.

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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

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silica gel 60 F254 plates, and the products were visualized by 1H NMR and

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C NMR (300

MHz and 75 MHz, respectively) spectra were recorded in CDCl3. Chemical shifts (δ) are

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reported in ppm using TMS as internal standard, and spin-spin coupling constants (J) are

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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):

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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

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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

ACCEPTED MANUSCRIPT 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

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condenser under an air atmosphere at room temperature. Then, TBHP (70% aqueous solution,

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1 equiv) was added to the reaction mixture, and the mixture was placed in an oil bath with

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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

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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

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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-

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hexane/ethyl acetate) to afford the desired product 7a.

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Analytical data of some selected compounds 1-Oxo-1-phenylpropan-2-yl benzoate (4a): Following the general procedure, the product

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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),

Ar);

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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, 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.

ACCEPTED MANUSCRIPT 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 chromatography; M. p. 45 ºC; 1H 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,

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129.9, 131.3, 133.7, 134.4, 165.1, and 196.5; MS (EI, 70 eV): m/z (%) = 288 (M+, 5), 244

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(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

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procedure, the product 4f was obtained as yellow liquid in 60% (0.093gr) yield after column

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chromatography. 1H NMR (300 MHz, CDCl3): δ 1.2 (s, 9H, 3 × CH3), 1.58 (d, J = 6.8 Hz, 3H), 6.12 (q, J = 6.8 Hz, CH), 7.18–7.52 (m, 5H, Ar), 7.91–7.95 (m, 4H, Ar);

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C NMR

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(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,

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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

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chromatography; M. p. 93-96 ºC; 1H NMR (300 MHz, CDCl3): δ 1.5 (d, J = 9.6 Hz, 3H), 6.11

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(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, Ar), 8.0 (d, J = 9.6 Hz, 2H, Ar);

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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, CH), 3.79 (s, 3H, OCH3), 6.85 (d, J = 11.6 Hz,, 2H, Ar), 7.83 (d, 2H, J = 12 Hz, Ar);

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ACCEPTED MANUSCRIPT 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 chromatography; M. p. 180-185 ºC; 1H NMR (300 MHz, CDCl3): δ 0.91-0.95 (m, 2H, CH2),

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C NMR (CDCl3, 75 MHz): δ 10.9, 28.8, 29.7, 55.5,

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CH2), 8.08 (d, 2H, J = 7.2 Hz, Ar);

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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,

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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

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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,

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CH), 7.49–7.52 (m, 2H, Ar), 7.63–7.66 (m, 1H, Ar), 8.16–8.18 (m, 2H, Ar);

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C 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):

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m/z (%) = 280 (M+, 3), 115 (43), 105 (100), 77 (55), 43 (23).

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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

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chromatography. 1H NMR (300 MHz, CDCl3): δ 1.26 (t, J = 7.2 Hz, 6H, 2 × CH3), 4.24-4.28

1H, Ar).

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(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,

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 chromatography. 1H NMR (300 MHz, CDCl3): δ 1.23-1.28 (m, 6H, 2 × CH3), 4.22-4.29 (m, 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); 13C 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).

ACCEPTED MANUSCRIPT 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 chromatography. 1H 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,

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164.7, and 165.2. IR (KBr, cm-1): ν 2979, 2933, 1722, and 1690; MS (EI, 70 eV): m/z (%) =

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294 (M+, 20), 119 (100), 91 (85), 65 (45), 43 (25).

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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

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chromatography. 1H 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,

8.76 (s, 1H, Ar);

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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), C NMR (CDCl3, 75 MHz): δ 14.1, 14.2, 62.6, 72.3, 125.3, 125.7, 126.8,

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127.8, 128.4, 128.7, 129.5, 132.1, 132.4, 135.9, 164.6, 165.3, and 167.8.

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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

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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,

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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. 1

H NMR (300 MHz, CDCl3): δ 1.20-1.29 (m, 6H, 2 × CH3), 4.23-4.27 (m, 4H, 2 × CH2), 5.71

ACCEPTED MANUSCRIPT (s, CH), 7.63 (t, 1H, J = 8 Hz, Ar), 8.38–8.41 (m, 2H, Ar), 8.8 (s, 1H , Ar);

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(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. Tetraethyl ethene-1,1,2,2-tetracarboxylate (8(: 1H NMR (300 MHz, CDCl3): δ 1.251.33 (m, 12H, 4× CH2), 4.12–4.34 (m, 8H); 13C NMR (CDCl3, 75 MHz): δ 13.8, 62.5, 135.3

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and 162.3.

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Acknowledgements We are thankful to Persian Gulf University Research Council for partial support of this work.

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References 1. a) J. P. Hallet, T. Welton, Chem. Rev. 2011, 111, 3508; b) R. Hayes, Chem. Rev.

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2015, 115, 6357; c) A. S. Amarasekara, Chem. Rev. 2016, 116, 6133; d) C. Dai, J.

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Zhang, C. Huang, Z. Lei, Chem. Rev. 2017, 117, 6929; e) Y. Qiao, W. Ma, N. Theyssen, C. Chen, Z. Hou, Chem. Rev. 2017, 117, 6881. 2. a) Q. Zhang, K. D. O. Vigier, S. Royer, F. Jérôme, Chem. Soc. Rev. 2012, 41, 7108;

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b) M. Francisco, A.V.D. Bruinhorst,M.C. Kroon, Angew. Chem. Int. Ed. 2013, 52,3074; c) E. L. Smith, A. P. Abbott, K. S. Ryder. Chem. Rev. 2014, 114, 11060. 3. a) Y. A. Sonawane, S. B. Phadtare, B. N. Borse, A. R. Jagtap, G. S. Shankarling, Org.

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Lett. 2010, 12, 1456; b) A. P. Abbott, T. J. Bell, S. Handa, B. Stoddart, Green Chem.

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2005, 7, 705; c) R. C. Morales, V. Tambyrajah, P. R. Jenkins, D. L. Davies, A. P. Abbott, Chem.Commun. 2004, 2, 158. 4. a) G. Schwenker, K. Stiefvater, Arch. Pharm. 1991, 324, 547; b) E. Bratoeff, E. Ramı´rez, E. Flores, N. Valencia, M. Sa´nchez, I. Heuze, M. Cabeza, Chem. Pharm. Bull. 2003, 51, 1132; c) G. Scheid, W. Kuit, E. Ruijter, R. V. A. Orru, E. Henke, U. Bornscheuer, L. Wessjohann, Eur. J. Org. Chem. 2004, 1063; d) M. Shindo, Y. Yoshimura, M. Hayashi, H. Soejima, T. Yoshikawa, K. Matsumoto, K. Shishido, Org. Lett. 2007, 9, 1963; e) M. A. Ashraf, A. G. Russell, C. W. Wharton, Tetrahedron

ACCEPTED MANUSCRIPT 2007, 63, 586; f) R. N. Reddi, P. V. Malekar, A. Sudalai, Org. Biomol. Chem. 2013, 11, 6477. 5. a) J. Christoffers, A. Baro, T. Werner, Adv. Synth. Catal. 2004, 346, 143; b) N. Kaila, K. Janz, S. DeBernardo, P. W. Bedard, R. T. Camphausen, S. Tam, D. H. H. Tsao, J. C. Keith, C. Nickerson-Nutter, A. Shilling, R. Young-Sciame, Q. Wang, J. Med.

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Chem. 2007, 50, 21; c) J. J. Topczewski, J. D. Neighbors and D. F. Wiemer, J. Org.

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Chem. 2009, 74, 6965; d) J. F. Ma´rquez Ruiz, G. Radics, H. Windle, H. O. Serra, A.

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L. Simplı´cio, K. Kedziora, P. G. Fallon, D. P. Kelleher, J. F. Gilmer, J. Med. Chem. 2009, 52, 3205.

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6. a) S. J. Hecker, K. M. Werner, J. Org. Chem. 1993, 58, 1762; b) J. L. Wood, B. M. Stoltz, H.-J. Dietrich, D. A. Pflum, D. T. Petsch, J. Am. Chem. Soc. 1997, 119, 9641;

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c) L. Valgimigli, G. Brigati, G. Pedulli, G. A. Dilabio, M. Mastragostino, C. Arbizzani, D. A. Pratt, Chem. Eur. J. 2003, 9, 4997; d) M. Altuna-Urquijo, S. P.

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Stanforth, B. Tarbit, Tetrahedron Lett. 2005, 46, 6111; e) A. Gehre, S. P. Stanforth,

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B. Tarbit, Tetrahedron 2009, 65, 1115. 7. P. A. Levine, A. Walti, Org. Synth. Coll. Vol. II 1943, 5.

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8. For selected examples, see: a) M. E. Kuehne, T. C. Giacobbe, J. Org. Chem. 1968, 33, 3359; b) D. J. Rawilson, G. Sonovsky, Synthesis 1973, 567; c) G. J. Williams, N. R.

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Hunter, Can. J. Chem. 1976, 54, 3830; d) T. Satoh, S. Motohashi, K. Yamakawa, Bull. Chem. Soc. Jpn. 1986, 59, 946; e) J. C. Lee, Y. S. Jin, J.-H. Choi, Chem. Commun. 2001, 956. 9. T. Shinda, T. Kawakami, H. Sakai, I. Takada, Y. Ohfune, Tetrahedron Lett. 1998, 39, 3757.

ACCEPTED MANUSCRIPT 10. a) C. S. Beshara, A. Hall, R. L. Jenkins, K. L. Jones, N. M. Killeen, P. H. Taylor, S. P. Thomas, N. C. O. Tomkinson, Org. Lett. 2005, 7, 5729; b) D. A. Smithen, C. J. Mathews, N. C. O. Tomkinson, Org. Biomol. Chem. 2012, 10, 3756. 11. M. Ochiai, Y. Takeuchi, T. Katayama, T. Seuda, K. Miyamito, J. Am. Chem. Soc. 2005, 127, 12244.

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12. M. Uyanik, D. Suzuki, T. Yasui, K. Ishihara, Angew. Chem. Int. Ed. 2011, 50, 5331.

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13. S. Guo, J.-T. Yu, Q. Dai, H. Yang, J. Cheng, Chem. Commun. 2014, 50, 6240.

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14. B. Mondal, S. C. Sahoo, S. C. Pan, Eur. J. Org. Chem. 2015, 3135. 15. G. Majji, S. Guin, S. K. Rout, A. Behera, B. K. Patel, Chem. Commun. 2014, 50,

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12193.

16. For recent reports of an α-carbonyl radical, see: a) P. S. Baran, J. M. Richter, J. Am.

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Chem. Soc. 2004, 126, 7450; b) J. M. Richter, B. W. Whitefield, T. J. Maimone, D. W. Lin, M. P. Castroviejo, P. S. Baran, J. Am. Chem. Soc. 2007, 129, 12857; c) M. P.

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DeMartino, K. Chen, P. S. Baran, J. Am. Chem. Soc. 2008, 130, 11546; d) K. Xu, Y.

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Fang, Z. Yan, Z. Zha, Z. Wang, Org. Lett. 2013, 15, 2148. 17. a) J. Xie, H. Jiang, Y. Cheng, C. Zhu, Chem. Commun. 2012, 48, 979; b) Y. Yuan, W.

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Hou, D. Zhang-Negrerie, K. Zhao, Y. Du, Org. Lett. 2014, 16, 5410; c) L. Ma, X. Wang, W. Yu, B. Han, Chem. Commun. 2011, 47, 11333.

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18. a) Z. Liu, J. Zhang, S. Chen, E. Shi, Y. Xu, X.Wan, Angew. Chem. Int. Ed. 2012, 51, 3231; b) E. Shi, Y. Shao, S. Chen, H. Hu, Z. Liu, J. Zhang, X. Wan, Org. Lett. 2012, 14, 3384.

ACCEPTED MANUSCRIPT

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

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Dariush Saberi,* Neda Manouchehri, and Khodabakhsh Niknam*

ACCEPTED MANUSCRIPT 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

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 Synthesis of -acyloxyl-carbonyl compounds in acceptable yields