A method for preparing an aromatic ketone compound containing a bis-arylmethane structure
By combining phosphorus trichloride and elemental iodine, aromatic ketone compounds containing diarylmethane structures can be synthesized in an air atmosphere in the next step. This solves the problems of excessive use of metal promoters and environmental unfriendliness in existing technologies, and achieves efficient and green compound preparation.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- HUNAN UNIV OF SCI & TECH
- Filing Date
- 2021-12-03
- Publication Date
- 2026-06-16
Smart Images
Figure CN117776883B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a method for preparing aromatic ketone compounds containing a diarylmethane structure, belonging to the field of fine chemical synthesis. Background Technology
[0002] Aromatic ketones containing diarylmethane structures play a crucial role due to the simultaneous inclusion of both diarylmethane and aromatic ketone structures. Diarylmethane and aromatic ketones are important organic synthesis intermediates, possessing complex structural units and widely found in natural products, drug molecules, and various bioactive substances. Furthermore, diarylmethane compounds are also widely used in fragrances, dyes, and aromatic solvents. Therefore, researching and developing efficient and environmentally friendly new synthetic routes for aromatic ketones containing diarylmethane structures has significant practical value and scientific research significance.
[0003] According to relevant literature and patent reports, the preparation of aromatic ketone compounds containing a diarylmethane structure mainly falls into the following categories:
[0004] The first method involves preparation via traditional Friedel-Crafts alkylation, using benzyl halides containing diaryl ketones as raw materials and an equivalent metal Lewis acid (such as aluminum trichloride) as a promoter, reacting with aromatic hydrocarbons to obtain the product (Formula 1). However, this method has drawbacks, including the need for excessive metal promoters, difficult post-processing, environmental unfriendliness, poor selectivity, and numerous byproducts.
[0005]
[0006] The second method involves preparation via the traditional Friedel-Crafts acylation reaction, using diarylmethane as a raw material and an equivalent amount of Lewis metal acid (such as aluminum trichloride) as a promoter, reacting with aromatic acyl chlorides to obtain the product (Equation 2). This method also requires an excess of metal promoter, is difficult to process, is environmentally unfriendly, has poor selectivity, and produces numerous byproducts.
[0007]
[0008] In addition, a few methods employ coupling reactions, using organometallic reagents and corresponding coupling substrates to catalyze the coupling of these compounds. There are also a few reports of using electrochemical selective oxidation to prepare aromatic ketones with diarylmethane structures. However, these methods often require either the use of equivalent organometallic reagents and metal catalysts under inert gas protection, or the use of oxygen and electrode assistance, resulting in limited raw material sources, reduced reaction operability, and increased costs, thus restricting their application scope to some extent.
[0009] Therefore, we urgently need to develop new, inexpensive, green, low-toxicity, and efficient methods to overcome the shortcomings of the above methods and provide new pathways for the synthesis of aromatic ketone compounds containing diarylmethane structures. Summary of the Invention
[0010] To address the problems existing in the preparation of aromatic ketone compounds containing a diarylmethane structure, the present invention aims to provide a method for preparing aromatic ketone compounds containing a diarylmethane structure using inexpensive and readily available phosphorus trichloride as a reducing reagent precursor and elemental iodine as a promoter. This method starts from p-formylaryl carbamate and, in the presence of phosphorus trichloride and elemental iodine, efficiently synthesizes the corresponding aromatic ketone compounds containing a diarylmethane structure in one step with aromatic compounds. This method avoids the use of equivalent metal reagents or metal catalysts and inert atmosphere protection, and has the advantages of simple reaction conditions, easy operation, environmental friendliness, high yield, and suitability for industrial production.
[0011] To achieve the above objectives, the present invention adopts the following technical solution:
[0012] A method for preparing aromatic ketone compounds containing a diarylmethane structure involves heating and reacting a formylaryl carboxylate ester and an aromatic compound in the presence of phosphorus trichloride and iodine under an air atmosphere to obtain aromatic ketone compounds containing a diarylmethane structure. The reaction equation is shown in Formula 3.
[0013]
[0014] In the formula, R is selected from alkyl, aryl, heterocyclic aryl, benzyl, and cinnamyl; the aryl group in p-formylaryl carbamate is selected from phenyl, naphthyl, and substituted phenyl.
[0015] In this invention, R can be selected from a wide range. R can be an alkyl group, preferably C1 to C2. 10 Alkyl groups, C1-C 10 The alkyl group can be a straight-chain alkyl group or a branched alkyl group, or a cycloalkyl group, such as methyl, ethyl, propyl, tert-butyl, cyclopropyl, cyclohexyl, etc. R can be an aryl group, including phenyl, naphthyl, anthracene, phenanthryl, etc. R can be a heterocyclic aryl group, including five- or six-membered ring substituents, such as furan, thiophene, pyridine, etc. R can be a C1-C1 substituent group. 10 Alkyl groups, wherein the substituent-containing C1-C 10 The alkyl group can contain aryl, heterocyclic aryl, etc., on any one carbon atom. When the aryl group in p-formylarylformate is a substituted phenyl group, it is a phenyl group containing alkyl, alkoxy, halogen substituent, cyano, trifluoromethyl, nitro, etc., substituents from C1 to C5.
[0016] Preferably, the p-formylarylformate is selected from one of the following structural formulas:
[0017]
[0018] Preferably, the aromatic compound is selected from one of the following structural formulas:
[0019]
[0020] Preferably, the molar ratio of the p-formylaryl carbamate to the aromatic compound is not higher than 1:2, more preferably 1:8 to 16; the molar ratio of the p-formylaryl carbamate to phosphorus trichloride is 1:1 to 2, more preferably 1:1.2 to 1.5; and the molar ratio of the p-formylaryl carbamate to elemental iodine is 1:0.3 to 1, more preferably 1:0.5 to 1.0. In this invention, the aromatic compound serves as both a reactant and a solvent. Therefore, adding an excess of the aromatic compound during the reaction can further improve the yield of the aromatic ketone compound containing a diarylmethane structure.
[0021] Preferably, the specific process of the heating reaction is as follows: first react at 80-120°C for a reaction time of 12-24 hours, and then react at a temperature not lower than 160°C for a reaction time of 24-48 hours; or react directly at a temperature not lower than 160°C for a reaction time of at least 24 hours.
[0022] Preferably, after the heating reaction is completed, the reaction liquid is treated with sodium thiosulfate aqueous solution, extracted, dried and filtered, rotary evaporated, and then purified by column chromatography.
[0023] The present invention has the following beneficial effects:
[0024] This invention uses phosphorus trichloride, an inexpensive and readily available industrial raw material, as a reducing agent precursor and promoter. In the presence of elemental iodine, it efficiently prepares aromatic ketone compounds containing diarylmethane structures in a one-pot, one-step process starting from readily available p-formylaryl carbamates. It has the advantages of simple reaction conditions, easy operation, inexpensive and readily available reagents, high chemical selectivity, and environmental friendliness. It avoids the use of equivalent metal reagents, transition metal catalysts, and inert atmosphere protection, which is beneficial for industrial production. Attached Figure Description
[0025] Figure 1 The 1H NMR spectrum of the sample obtained in Example 1;
[0026] Figure 2 The carbon NMR spectrum of the sample obtained in Example 1;
[0027] Figure 3 The 1H NMR spectrum of the sample obtained in Example 2;
[0028] Figure 4 The carbon NMR spectrum of the sample obtained in Example 2;
[0029] Figure 5 The 1H NMR spectrum of the sample obtained in Example 3;
[0030] Figure 6 The carbon NMR spectrum of the sample obtained in Example 3;
[0031] Figure 7 The 1H NMR spectrum of the sample obtained in Example 4;
[0032] Figure 8 The carbon NMR spectrum of the sample obtained in Example 4;
[0033] Figure 9 The 1H NMR spectrum of the sample obtained in Example 5;
[0034] Figure 10 The carbon NMR spectrum of the sample obtained in Example 5; Detailed Implementation
[0035] The following examples are intended to further illustrate the present invention, but do not limit the scope of protection of the claims of the present invention.
[0036] Example 1
[0037] In an air atmosphere, methyl paraben (0.3 mmol), iodine (0.15 mmol), phosphorus trichloride (0.36 mmol), and mesitylene (0.6 mL) were added to a reaction flask. The mixture was first stirred at 100 °C for 18 hours, then heated to 160 °C and stirred for another 36 hours. After the reaction was complete, a 5% (w / w) aqueous solution of Na₂S₂O₃ was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product. The obtained product was a pale yellow solid. The yield was 75%.
[0038] 1 H NMR(500MHz, CDCl3) δ7.66(d,J=7.9Hz,2H),7.07(d,J=8.2Hz,2H),6.89(s,2H) ,6.86(s,2H),4.05(s,2H),2.31(s,3H),2.28(s,3H),2.18(s,6H),2.06(s,6H).
[0039] 13 C NMR (126MHz, CDCl3) δ200.5,146.7,138.3,137.1,136.9,136.1,135.2,134.1,132.9,129.7,129.0,128.3,128.3,35.0,21.2,20.9,20.2,19.4.
[0040] Example 2
[0041] In an air atmosphere, methyl 4-formyl-3-methoxybenzoate (0.3 mmol), iodine (0.15 mmol), phosphorus trichloride (0.36 mmol), and mesitylene (0.6 mL) were added to a reaction flask. The mixture was first stirred at 100 °C for 18 hours, then heated to 160 °C and stirred for 36 hours. After the reaction was complete, a 5% (w / w) Na₂S₂O₃ aqueous solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product. The obtained product was a pale yellow solid. The yield was 71%.
[0042] 1 H NMR(500MHz, CDCl3)δ7.55(s,1H),6.94(d,J=7.6Hz,1H),6.87(s,2H),6.83(s,2H),6.50(d, J=7.8Hz,1H),3.97(s,3H),3.95(s,2H),2.29(s,3H),2.27(s,3H),2.13(s,6H),2.06(s,6H).
[0043] 13 C NMR (126MHz, CDCl3) δ200.6,157.9,138.3,137.2,137.1,136.4,135.8,135.3,134 .1,132.6,128.9,128.2,127.6,123.7,108.3,55.6,28.9,21.1,20.9,19.9,19.4.
[0044] Example 3
[0045] In an air atmosphere, methyl 4-formyl-3-chlorobenzoate (0.3 mmol), iodine (0.21 mmol), phosphorus trichloride (0.36 mmol), and mesitylene (0.6 mL) were added to a reaction flask. The mixture was first stirred at 100 °C for 18 hours, then heated to 160 °C and stirred for 36 hours. After the reaction was complete, a 5% (w / w) Na₂S₂O₃ aqueous solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product. The obtained product was a pale yellow solid. The yield was 72%.
[0046] 1H NMR (500MHz, CDCl3) δ7.85 (s, 1H), 7.42 (d, J = 8.1Hz, 1H), 6.90 (s, 2H), 6.86 (s, 2H), 6. 64(d,J=8.0Hz,1H),4.06(s,2H),2.31(s,3H),2.29(s,3H),2.13(s,6H),2.06(s,6H).
[0047] 13 C NMR (126MHz, CDCl3) δ199.3,143.8,138.7,137.1,136.7,136.4,135.1,134.1, 131.8,129.7,129.1,128.6,128.4,127.9,125.6,32.8,21.1,20.9,19.9,19.4.
[0048] Example 4
[0049] In an air atmosphere, methyl 4-formyl-3-bromobenzoate (0.3 mmol), iodine (0.21 mmol), phosphorus trichloride (0.36 mmol), and mesitylene (0.6 mL) were added to a reaction flask. The mixture was first stirred at 100 °C for 18 hours, then heated to 160 °C and stirred for 36 hours. After the reaction was complete, a 5% (w / w) aqueous solution of Na₂S₂O₃ was added, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product. The obtained product was a pale yellow solid. The yield was 71%.
[0050] 1 H NMR (500MHz, CDCl3) δ8.05 (s, 1H), 7.44 (d, J = 8.0Hz, 1H), 6.90 (s, 2H), 6.86 (s, 2H), 6. 62(d,J=8.1Hz,1H),4.03(s,2H),2.30(s,3H),2.29(s,3H),2.13(s,6H),2.06(s,6H).
[0051] 13 C NMR (126MHz, CDCl3) δ199.2,145.4,138.7,137.1,136.9,136.4,136.3,134.1, 133.0,132.0,129.1,128.7,128.6,128.4,125.7,35.8,21.2,21.0,20.0,19.4.
[0052] Example 5
[0053] In an air atmosphere, methyl 4-formyl-1-naphthoate (0.3 mmol), iodine (0.15 mmol), phosphorus trichloride (0.36 mmol), and mesitylene (0.6 mL) were added to a reaction flask. The mixture was first stirred at 100 °C for 18 hours, then heated to 160 °C and stirred for 36 hours. After the reaction was complete, a 5% (w / w) Na₂S₂O₃ aqueous solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product. The obtained product was a yellow oily liquid. The yield was 57%.
[0054] 1 H NMR (500MHz, CDCl3) δ9.36 (s, 1H), 8.35 (s, 1H), 7.72 (d, J = 20.8Hz, 2H), 7.41 (s, 1H), 6.9 0(s,2H),6.83(s,2H),6.59(s,1H),4.43(s,2H),2.31-2.23(m,6H),2.15-2.04(s,12H).
[0055] 13 C NMR (126MHz, CDCl3) δ202.7,142.5,138.8,138.5,137.3,136.2,134.6,132.9,132.9,132.8, 132.3,131.0,129.1,128.4,128.3,127.1,126.7,123.5,122.6,32.1,21.2,21.0,20.0,19.5.
[0056] Example 6
[0057] In an air atmosphere, methyl paraben (0.3 mmol), iodine (0.15 mmol), phosphorus trichloride (0.36 mmol), and mesitylene (0.6 mL) were added to a reaction flask, and the mixture was stirred at 160 °C for 36 hours. After the reaction was complete, a 5% (w / w) aqueous solution of Na₂S₂O₃ was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product. The obtained product was a pale yellow solid. The yield was 53%. The NMR data were the same as in Example 1.
[0058] Example 7
[0059] Under air atmosphere, 0.3 mmol of hexyl p-formylbenzoate, 0.3 mmol of iodine, 0.36 mmol of phosphorus trichloride, and 0.6 mL of mesitylene were added to a reaction flask. The mixture was first stirred at 100 °C for 18 hours, then heated to 160 °C and stirred for 36 hours. After the reaction was complete, a 5% (w / w) aqueous solution of Na₂S₂O₃ was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product. The obtained product was a pale yellow solid. The yield was 78%. The NMR data were the same as in Example 1.
[0060] Example 8
[0061] In an air atmosphere, cyclohexyl p-formylbenzoate (0.3 mmol), iodine (0.15 mmol), phosphorus trichloride (0.36 mmol), and mesitylene (0.6 mL) were added to a reaction flask. The mixture was first stirred at 100 °C for 18 hours, then heated to 160 °C and stirred for 36 hours. After the reaction was complete, a 5% (w / w) Na₂S₂O₃ aqueous solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product. The obtained product was a pale yellow solid. The yield was 77%. The NMR data were the same as in Example 1.
[0062] Example 9
[0063] In an air atmosphere, phenyl p-formylbenzoate (0.3 mmol), iodine (0.15 mmol), phosphorus trichloride (0.36 mmol), and mesitylene (0.6 mL) were added to a reaction flask. The mixture was first stirred at 100 °C for 18 hours, then heated to 160 °C and stirred for 36 hours. After the reaction was complete, a 5% (w / w) Na₂S₂O₃ aqueous solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product. The obtained product was a pale yellow solid. The yield was 40%. The NMR data were the same as in Example 1.
[0064] Example 10
[0065] In an air atmosphere, cinnamyl benzoate (0.3 mmol), iodine (0.15 mmol), phosphorus trichloride (0.45 mmol), and mesitylene (0.6 mL) were added to a reaction flask. The mixture was first stirred at 100 °C for 18 hours, then heated to 160 °C and stirred for 36 hours. After the reaction was complete, a 5% (w / w) Na₂S₂O₃ aqueous solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product. The obtained product was a pale yellow solid. The yield was 52%. The NMR data were the same as in Example 1.
Claims
1. A method for preparing an aromatic ketone compound containing a diarylmethane structure, characterized in that: In an air atmosphere, 0.3 mmol of methyl 4-formyl-1-naphthoate, 0.15 mmol of iodine, 0.36 mmol of phosphorus trichloride, and 0.6 mL of mesitylene were added to a reaction flask. The mixture was first stirred at 100 °C for 18 hours, then heated to 160 °C and stirred for 36 hours. After the reaction was completed, a 5% (w / w) Na₂S₂O₃ aqueous solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered, and evaporated to dryness before being separated by column chromatography to obtain the product.