An aryl carboxylate compound and a method for preparing the same
By using chloroformate or its derivatives with aryl iodine and other compounds in specific solvents under an inert atmosphere to prepare aryl carboxylic acid esters, the problems of harsh esterification reaction conditions and low yields have been solved, achieving high yields and wide applicability, with readily available raw materials and simple preparation.
Patent Information
- Application Number
- CN202310681739.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-06-09
- Publication Date
- 2025-12-23
- Estimated Expiration
- 2043-06-09
AI Technical Summary
Existing esterification reaction conditions are harsh, yields are low, and substrate adaptability is limited. There is a need to develop novel esterification reaction systems that are mild and widely adaptable.
Aryl carboxylic acid esters are prepared by reacting chloroformate or its derivatives, aryl iodine, ligands, reducing agents, additives and catalysts under an inert atmosphere, using a mixed solution of anhydrous acetonitrile and anhydrous dimethylacetamide as the solvent, and by stirring.
It achieves mild reaction conditions, broad substrate adaptability, high yield of up to 80%, low raw material cost and easy availability, and simple preparation method.
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Figure CN116655467B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of organic chemistry, and particularly relates to an aryl carboxylate compound and a preparation method thereof. BACKGROUND
[0002] Aryl carboxylate compounds exist widely in life and play an important role in bioactive natural products, drugs, materials and biofuels.
[0003] The traditional esterification reaction is a reversible reaction with low yield, and the product or alcohol needs to be removed continuously or the amount of alcohol needs to be greatly excessive to promote the reaction to proceed in the forward direction. Moreover, the early developed esterification reactions have great limitations, and they are all limited to specific reactants.
[0004] In summary, the early esterification reaction system has great defects, and it is particularly urgent to develop a new esterification reaction system with mild reaction conditions and wide substrate adaptability, so it is a technical problem to be solved to find a new esterification reaction system with mild reaction conditions and wide substrate adaptability. SUMMARY
[0005] The present application relates to the technical field of organic chemistry, and particularly relates to an aryl carboxylate compound and a preparation method thereof.
[0006] The object of the present application can be achieved by the following technical solutions.
[0007] The present application provides a preparation method of an aryl carboxylate compound, comprising the following steps:
[0008] S1, under an inert atmosphere, dissolving chloroformate or its derivative, aryl iodine, ligand, reducing agent, additive and catalyst in a solvent to obtain a reaction solution;
[0009] S2, stirring the reaction solution obtained in step S1 to obtain an aryl carboxylate compound with a structure as shown in formula III,
[0010]
[0011] wherein, R 1 is selected from any one of H, 4-trifluoromethyl, 4-methoxy and 4-methyl formate, and R 2 is selected from any one of 4-trifluoromethyl, 4-acetyl and 4-methyl formate.
[0012] Further, in step S1, the inert atmosphere is nitrogen.
[0013] Further, in step S1, the chloroformate or its derivative is a compound with a structure as shown in formula I.
[0014]
[0015] wherein R 1 is selected from any one of H, 4-trifluoromethyl, 4-methoxy, 4-methyl formate.
[0016] Further, in the step S1, the aryl iodide is a compound with a structure as shown in formula II,
[0017]
[0018] R 2 is selected from any one of 4-trifluoromethyl, 4-acetyl, 4-methyl formate.
[0019] Further, in the step S1, the ligand is selected from any one of nitrogen-containing heterocyclic compounds and derivatives thereof; the reducing agent is zinc powder; the additive is selected from any one or more of anhydrous magnesium bromide, anhydrous lithium bromide; and the catalyst is selected from any one of nickel metal and derivatives thereof.
[0020] Still further, the ligand is 4,4-dimethyl-2,2-bipyridine, and the catalyst is Ni(acac)2.
[0021] Further, in the step S1, the solvent is a mixture of anhydrous acetonitrile and anhydrous dimethylacetamide in a volume ratio of 4:1.
[0022] Further, in the step S1, the molar ratio of chloroformate or its derivative, aryl iodide, ligand, reducing agent, additive, and catalyst is (1.0-2.0):1:(0.10-0.15):(2.0-3.0):(1.0-4.0):(0.05-0.15).
[0023] Further, in the step S2, the stirring temperature is 40℃, and the stirring time is 8-12h.
[0024] The reaction formula is as shown below:
[0025]
[0026] The second technical solution of the present application provides an aryl carboxylate compound prepared by the preparation method of the first technical solution.
[0027] Compared with the prior art, the present application has the following beneficial effects:
[0028] (1) The aryl carboxylate compound is prepared by using chloroformate or its derivative and aryl iodide as substrates, the reaction conditions are mild, the substrates have wide adaptability, and the yield is as high as 80%.
[0029] (2) The raw material cost is low and easy to obtain, and the preparation conditions are simple and easy to realize. BRIEF DESCRIPTION OF DRAWINGS
[0030] Figure 1 The hydrogen spectrum of the aryl carboxylate compound shown as structural formula III-1.
[0031] Figure 2 The carbon spectrum of the aryl carboxylate compound shown as structural formula III-1.
[0032] Figure 3 The hydrogen spectrum of the aryl carboxylate compound shown as structural formula III-2.
[0033] Figure 4 The carbon spectrum of the aryl carboxylate compound shown as structural formula III-2.
[0034] Figure 5 The fluorine spectrum of the aryl carboxylate compound shown as structural formula III-2.
[0035] Figure 6 The hydrogen spectrum of the aryl carboxylate compound shown as structural formula III-3.
[0036] Figure 7 The carbon spectrum of the aryl carboxylate compound shown as structural formula III-3.
[0037] Figure 8 The hydrogen spectrum of the aryl carboxylate compound shown as structural formula III-4.
[0038] Figure 9 The carbon spectrum of the aryl carboxylate compound shown as structural formula III-4.
[0039] Figure 10 The hydrogen spectrum of the aryl carboxylate compound shown as structural formula III-5.
[0040] Figure 11 The carbon spectrum of the aryl carboxylate compound shown as structural formula III-5.
[0041] Figure 12 The fluorine spectrum of the aryl carboxylate compound shown as structural formula III-5.
[0042] Figure 13 The hydrogen spectrum of the aryl carboxylate compound shown as structural formula III-6.
[0043] Figure 14 The carbon spectrum of the aryl carboxylate compound shown as structural formula III-6. DETAILED DESCRIPTION
[0044] The application will be described in detail below with reference to the accompanying drawings and specific examples.
[0045] In the following examples and comparative examples, unless otherwise specified, the raw materials or processing techniques are all conventional commercially available raw material products or conventional processing techniques in the art.
[0046] The preparation method of the secondary chloroformate includes the following steps:
[0047] (1) Synthesis of secondary alkyl alcohol:
[0048] To a solution of triethylamine (3.5 mL, 25 mmol, 2.5 equiv) in DCM (20 mL) was added the compound of structure B (0.91 g, 12 mmol, 1.2 equiv) and the mixture was cooled to -5 °C. The compound of structure A (10 mmol) was added dropwise to the above mixture at a very slow rate over 1 hour and the reaction was continued to be stirred slowly at -5 °C for 12 hours. After the reaction was monitored to be completed by TLC plate, the reaction was quenched with saturated NaHCO3 aqueous solution (20 mL) and extracted with DCM (3 x 20 mL). The combined organic layers were dried over anhydrous MgSO4 and concentrated to give the corresponding secondary alcohol crude product, i.e. secondary alkyl alcohol.
[0049] The reaction scheme is shown below:
[0050]
[0051] (2) Synthesis of non-activated alkyl chloroformate:
[0052] A solution of triphosgene (1.78 g, 6.0 mmol, 0.6 equiv) in DCM (20 mL) was added dropwise to a solution of the alcohol (10.0 mmol, 1.0 equiv) and triethylamine (1.6 mL, 12.0 mmol, 1.2 equiv) in DCM (20 mL) at 0 °C over 0.5 hours. The resulting mixture was slowly warmed to room temperature and stirred for 4-5 hours. After the reaction was monitored to be completed by TLC plate, the reaction was quenched with saturated NaHCO3 aqueous solution (10 mL) and extracted with DCM (3 x 15 mL). The combined organic layers were dried over anhydrous MgSO4 and concentrated. The residue was purified by flash chromatography on silica gel to give the target product.
[0053] The reaction scheme is shown below:
[0054]
[0055] When Ar is , the obtained product has the structure shown in I-1;
[0056] When Ar is the resulting product has the structure shown in I-2;
[0057] When Ar is the resulting product has the structure shown in I-3;
[0058] When Ar is the resulting product has the structure shown in I-4.
[0059] The structures of I-1, I-2, I-3 and I-4 are as follows, respectively:
[0060]
[0061] Example 1:
[0062] In this example, aryl carboxylate compounds are synthesized using a secondary chloroformate and an aryl iodide containing a methyl formate substituent as raw materials, and the structure is shown in III-1:
[0063]
[0064] The specific preparation method comprises the following steps:
[0065] A dry Schlenk tube is sequentially added with a compound having the structure shown in I-1 (0.45 mmol, 108.9 mg, 150 mol%), methyl p-iodobenzoate (0.3 mmol, 78.6 mg, 100 mol%), anhydrous magnesium bromide (0.3 mmol, 27.3 mg, 100 mol%), anhydrous lithium bromide (0.9 mmol, 78.1 mg, 300 mol%), zinc powder (0.9 mmol, 58.8 mg, 300 mol%), Ni(acac)2(0.03 mmol, 7.7 mg, 10 mol%), 4,4-dimethyl-2,2-bipyridine (0.045 mmol, 8.1 mg, 15 mol%), and finally 1 mL of a mixed solvent of acetonitrile and dimethylacetamide (ratio of 4:1), and stirred at 40°C for 12 h. After the reaction is completed, no post-treatment is required, and column chromatography is directly used for separation (eluent is a mixture of ethyl acetate and petroleum ether in a volume ratio of 1:9) to obtain a white solid with a yield of 70-75%.
[0066] The aryl carboxylate compound having the structure shown in III-1 is subjected to nuclear magnetic resonance characterization, as shown in Figures 1-2 The specific data are as follows:
[0067] 1 H NMR(400 MHz, CHLOROFORM-D) δ 8.16 - 7.99 (m, 4H), 8.00 (m, 2H), 7.59 - 7.47 (m, 1H), 7.47 - 7.34 (m, 2H), 5.54 (m, 1H), 4.58 - 4.39 (m, 2H), 3.91 (s, 3H), 1.47 (d, J = 6.5 Hz, 3H).
[0068] 13 C NMR (101 MHz, CHLOROFORM-D) δ 166.4, 166.3, 165.3, 134.1, 133.3, 130.3, 129.8, 129.7, 129.7, 128.5, 127.3, 69.6, 66.6, 52.5, 16.7.
[0069] Example 2:
[0070] In this example, aryl carboxylate compounds were synthesized using di- secondary chloroformate and aryl iodine containing methyl formate substituent as raw materials, and the structural formula is shown as III-2:
[0071]
[0072] The specific preparation method comprises the following steps: sequentially adding a compound with a structure as shown in formula I-2 (0.45 mmol, 139.5 mg, 150 mol %), methyl p-iodobenzoate (0.3 mmol, 78.6 mg, 100 mol %), anhydrous magnesium bromide (0.3 mmol, 27.3 mg, 100 mol %), anhydrous lithium bromide (0.9 mmol, 78.1 mg, 300 mol %), zinc powder (0.9 mmol, 58.8 mg, 300 mol %), Ni(acac)2 (0.03 mmol, 7.7 mg, 10 mol %), 4,4-dimethyl-2,2-bipyridine (0.045 mmol, 8.1 mg, 15 mol %) into a dry Schlenk tube, and finally injecting 1 mL of a mixed solvent of acetonitrile and dimethylacetamide (in a ratio of 4:1), stirring at 40°C for 12 h, and after the reaction is completed, directly separating by column chromatography (eluent: a mixture of ethyl acetate and petroleum ether in a volume ratio of 1:9) without post-treatment to obtain a white solid with a yield of 70-75 %.
[0073] The aryl carboxylate compound with a structural formula as shown in III-2 is characterized by nuclear magnetic resonance, as shown in formula III-2, and the specific data are as follows: Figures 3-5
[0074] 1 H NMR (400 MHz, CHLOROFORM-D) δ 8.12 - 8.02 (m, 6H), 7.69 - 7.64 (m, 2H), 5.56 (m, 1H), 4.67 - 4.44 (m, 2H), 3.91 (d, J = 2.4 Hz, 3H), 1.48 (d, J = 6.6 Hz, 3H).
[0075] 13 C NMR (101 MHz, CHLOROFORM-D) δ 166.3, 165.2, 165.1, 134.4 (C-F, q, 2 J C-F = 32.7 Hz), 134.2, 133.5, 133.0, 130.2, 129.7, 126.3 (C-F, q, 1 J C-F = 269.3 Hz), 125.6 (C-F, q, 3 J C-F = 3.9 Hz), 69.4, 67.1, 52.6, 16.7.
[0076] 19 F NMR (376 MHz, CHLOROFORM-D) δ -63.06.
[0077] Example 3:
[0078] In this example, aryl carboxylate compounds were synthesized using di- secondary chloroformate and aryl iodine containing methyl formate substituent as raw materials, and the structural formula is shown as III-3:
[0079]
[0080] The specific preparation method comprises the following steps: sequentially adding a compound with a structure as shown in formula I-3 (0.45 mmol, 122.4 mg, 150 mol %), methyl p-iodobenzoate (0.3 mmol, 78.6 mg, 100 mol %), anhydrous magnesium bromide (0.3 mmol, 27.3 mg, 100 mol %), anhydrous lithium bromide (0.9 mmol, 78.1 mg, 300 mol %), zinc powder (0.9 mmol, 58.8 mg, 300 mol %), Ni(acac)2 (0.03 mmol, 7.7 mg, 10 mol %), 4,4-dimethyl-2,2-bipyridine (0.045 mmol, 8.1 mg, 15 mol %) into a dry Schlenk tube, and finally injecting 1 mL of a mixed solvent of acetonitrile and dimethylacetamide (in a ratio of 4:1) to be stirred at 40 °C for 12 h; after the reaction is completed, the product is directly separated by column chromatography (eluent: a mixed solution of ethyl acetate and petroleum ether in a volume ratio of 1:9) without post-treatment, and a white solid is obtained, with a yield of 60-65 %.
[0081] The aryl carboxylate compound with a structure as shown in formula III-3 is subjected to nuclear magnetic characterization, as shown in the following formula: Figures 6-7
[0082] 1 H NMR (400 MHz, CHLOROFORM-D) δ 8.11-8.02 (m, 4H), 7.97-7.90 (m, 2H), 6.92-6.84 (m, 2H), 5.52 (m, 1H), 4.51-4.41 (m, 2H), 3.92 (s, 3H), 3.81 (s, 3H), 1.46 (d, J = 6.5 Hz, 3H).
[0083] 13 C NMR (101 MHz, CHLOROFORM-D) δ 166.4, 166.1, 165.3, 163.6, 134.1, 134.0, 131.8, 129.7, 129.6, 122.2, 113.8, 69.7, 66.3, 55.5, 52.5, 16.7.
[0084] Example 4:
[0085] In this example, the aryl carboxylate compound is synthesized by taking a secondary chloroformate and an aryl iodine containing a methyl formate substituent as raw materials, and the structure thereof is as shown in formula III-4:
[0086]
[0087] The specific preparation method comprises the following steps: sequentially adding a compound with a structure as shown in formula I-4 (0.45 mmol, 135.0 mg, 150 mol%), methyl p-iodobenzoate (0.3 mmol, 78.6 mg, 100 mol%), anhydrous magnesium bromide (0.3 mmol, 27.3 mg, 100 mol%), anhydrous lithium bromide (0.9 mmol, 78.1 mg, 300 mol%), zinc powder (0.9 mmol, 58.8 mg, 300 mol%), Ni(acac)2 (0.03 mmol, 7.7 mg, 10 mol%), 4,4-dimethyl-2,2-bipyridine (0.045 mmol, 8.1 mg, 15 mol%) into a dry Schlenk tube, and finally injecting 1 mL of a mixed solvent of acetonitrile and dimethylacetamide (in a proportion of 4:1), stirring at 40°C for 12 hours, and directly separating a white solid with a yield of 75-80% by column chromatography without post-treatment after the reaction is completed (an eluent is a mixed liquid of ethyl acetate and petroleum ether in a volume ratio of 3:7).
[0088] The aryl carboxylate compound with the structural formula as shown in formula III-4 is subjected to nuclear magnetic characterization, as shown in formula III-4, and specific data are as follows. Figures 8-9
[0089] 1 H NMR (400MHz, CHLOROFORM-D) δ 8.06 (m, 8H), 5.55 (m, 1H), 4.51 (m, 2H), 3.91 (s, 6H), 1.47 (d, J = 6.5 Hz, 3H).
[0090] 13 C NMR (101MHz, CHLOROFORM-D) δ 166.3, 166.2, 165.5, 165.2, 134.2, 134.1, 133.9, 133.6, 129.7, 129.7, 69.5, 67.0, 52.6, 16.7.
[0091] Example 5:
[0092] In this example, the aryl carboxylate compound is synthesized by taking a secondary chloroformate and an aryl iodine containing a 4-trifluoromethyl substituent as raw materials, and the structural formula is as shown in formula III-5.
[0093]
[0094] The specific preparation method comprises the following steps: sequentially adding a compound with a structure as shown in Formula I-1 (0.45 mmol, 108.9 mg, 150 mol %), 4-trifluoromethyl iodobenzene (0.3 mmol, 81.6 mg, 100 mol %), anhydrous magnesium bromide (0.3 mmol, 27.3 mg, 100 mol %), anhydrous lithium bromide (0.9 mmol, 78.1 mg, 300 mol %), zinc powder (0.9 mmol, 58.8 mg, 300 mol %), Ni(acac)2 (0.03 mmol, 7.7 mg, 10 mol %), 4,4-dimethyl-2,2-bipyridine (0.045 mmol, 8.1 mg, 15 mol %) into a dry Schlenk tube, and finally injecting 1 mL of a mixed solvent of acetonitrile and dimethylacetamide (in a ratio of 4:1), stirring at 40°C for 12 h, and after the reaction is completed, directly separating by column chromatography (eluent: a mixture of ethyl acetate and petroleum ether in a volume ratio of 3:7) without post-treatment to obtain a white solid with a yield of 60-65 %.
[0095] The aryl carboxylate compound with a structure as shown in Formula III-5 is subjected to nuclear magnetic characterization, as shown in the following table: Figures 10-12
[0096] 1 H NMR (400 MHz, CHLOROFORM-D) δ 8.14 (m, 2H), 8.05-7.97 (m, 2H), 7.74-7.63 (m, 2H), 7.64-7.49 (m, 1H), 7.51-7.33 (m, 2H), 5.56 (m, 1H), 4.59-4.44 (m, 2H), 1.49 (d, J = 6.5 Hz, 3H).
[0097] 13 C NMR (101 MHz, CHLOROFORM-D) δ 166.3, 164.9, 134.6 (C-F, q, 2 J C-F = 32.5 Hz), 133.5, 133.3, 130.2, 129.8, 128.6, 125.5 (C-F, q, 3 J C-F = 3.9 Hz), 123.7 (C-F, q, 1 J C-F = 272.6 Hz), 69.8, 66.5, 16.7.
[0098] 19 F NMR (376 MHz, CHLOROFORM-D) δ -63.00.
[0099] Example 6:
[0100] In the present embodiment, the aryl carboxylate compound is synthesized using di- secondary chloroformate and aryl iodine containing 4-acetyl substituent as raw materials, and its structural formula is shown as III-6:
[0101]
[0102] The specific preparation method comprises the following steps: sequentially adding a compound with a structure shown as formula I-1 (0.45 mmol, 108.9 mg, 150 mol %), 4-iodoacetophenone (0.3 mmol, 73.8 mg, 100 mol %), anhydrous magnesium bromide (0.3 mmol, 27.3 mg, 100 mol %), anhydrous lithium bromide (0.9 mmol, 78.1 mg, 300 mol %), zinc powder (0.9 mmol, 58.8 mg, 300 mol %), Ni(acac)2 (0.03 mmol, 7.7 mg, 10 mol %), 4,4-dimethyl-2,2-bipyridine (0.045 mmol, 8.1 mg, 15 mol %) into a dry Schlenk tube, and finally injecting 1 mL of a mixed solvent of acetonitrile and dimethylacetamide (in a ratio of 4:1), stirring at 40 °C for 12 h, and directly separating by column chromatography (eluent: a mixture of ethyl acetate and petroleum ether in a volume ratio of 3:7) without post-treatment after the reaction is completed, to obtain a white solid with a yield of 70-75 %.
[0103] The aryl carboxylate compound with a structural formula shown as III-6 is subjected to nuclear magnetic characterization, as shown in the following formula: Figures 13-14 The specific data are as follows:
[0104] 1 H NMR (400 MHz, CHLOROFORM-D) δ 8.14-8.05 (m, 2H), 8.06-7.91 (m, 4H), 7.58-7.47 (m, 1H), 7.46-7.33 (m, 2H), 5.54 (m, 1H), 4.57-4.43 (m, 2H), 2.61 (s, 3H), 1.47 (d, J = 6.5 Hz, 3H).
[0105] 13 C NMR (101 MHz, CHLOROFORM-D) δ 197.7, 166.3, 165.2, 140.4, 134.0, 133.6, 133.3, 130.0, 129.7, 128.5, 128.3, 69.7, 66.6, 27.0, 16.7.
[0106] The foregoing description of the embodiments has been presented for the purpose of illustration and description. It is not intended to be exhaustive or to limit the application to the precise form disclosed. Modifications and variations are possible in light of the above teachings or can be acquired from practice of the application. As well, the description is presented in the context of the preferred embodiments as a number of alternatives. It is not intended to limit the application to the precise form described.
Claims
1. A method for producing an aryl carboxylate compound, characterized by, The method comprises the following steps: S1, dissolving chloroformate or its derivative, aryl iodine, ligand, reducing agent, additive and catalyst in solvent under inert atmosphere to obtain a reaction solution; S2, stirring the reaction solution obtained in S1 to obtain aryl carboxylate compound with structural formula as shown in III, ， wherein R is selected from any one of H, 4-trifluoromethyl, 4-methoxy, 4-methyl formate group, R 1 is selected from any one of H, 4-trifluoromethyl, 4-methoxy, 4-methyl formate group, R 2 is selected from any one of H, 4-trifluoromethyl, 4-methoxy, 4-methyl formate group. In S1, the chloroformate or its derivative is a compound with structural formula as shown in I, ， wherein R is selected from any one of H, 4-trifluoromethyl, 4-methoxy, 4-methyl formate group; 1 group is selected from any one of H, 4-trifluoromethyl, 4-methoxy, 4-methyl formate group; The aryl iodine is a compound with structural formula as shown in II, ， R 2 any one selected from the group consisting of 4-trifluoromethyl, 4-acetyl, 4-methyl formate; The ligand is 4,4-dimethyl-2,2-bipyridine; the reducing agent is zinc powder; the additive is selected from any one or more of anhydrous magnesium bromide and anhydrous lithium bromide; and the catalyst is Ni(acac)2; The solvent is a mixture of anhydrous acetonitrile and anhydrous dimethylacetamide with a volume ratio of 4:1; The molar ratio of chloroformate or its derivative, aryl iodine, ligand, reducing agent, additive and catalyst is (1.0-2.0):(1):(0.10-0.15):(2.0-3.0):(1.0-4.0):(0.05-0.15).
2. The method for preparing the aryl carboxylic acid ester compound according to claim 1, characterized in that, In S1, the inert atmosphere is nitrogen.
3. The method for preparing the aryl carboxylic acid ester compound according to claim 1, characterized in that, In S2, the stirring temperature is 40 DEG C, and the stirring time is 8-12 h.