A method for preparing aromatic ketone compounds and intermediates

Abstract

The present invention provides a novel method for preparing aromatic ketone compounds and intermediates. The method avoids the use of toxic and harmful reagents in the prior art, has mild reaction conditions, is less corrosive to equipment, has wide applicability, does not require special equipment, and is suitable for industrial production.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and in particular relates to a method for preparing aromatic ketone compounds and intermediates. Background Art

[0002] Aromatic ketones are a class of compounds with biological activity. For example, patent CN103360228A reports that bupropion (A) can be used to treat depression, while patent CN101066944A reports that sulcotrione (B) can be used to control broadleaf weeds and grass weeds in corn fields.

[0003]

[0004] Aromatic ketone compounds are an important class of organic synthesis intermediates. For example, they can be used as pharmaceutical intermediates to prepare atorvastatin (CN101306988B), a drug for treating high cholesterol and hyperlipidemia; ipriflavone (CN1048716C), a drug for treating osteoporosis; chalcone analogs (CN107216243B), an anti-tumor drug; and parecoxib sodium (CN111153865A). Aromatic ketone compounds can also be used as pesticide intermediates to prepare the plant growth regulator pyrimethamine (CN102532038B).

[0005] There are several main methods for synthesizing aromatic ketones.

[0006] The first method for preparing aromatic ketone compounds is to use phenylacetic acid as a raw material and react it with PCl3 or SOCl2 to produce phenylacetyl chloride, which is then reacted with benzene under the catalysis of anhydrous AlCl3 to produce the target compound (CN108440259A); the reaction formula is as follows:

[0007]

[0008] This method uses dangerous and highly corrosive chemicals PCl3 and SOCl2, which are very dangerous; phenylacetic acid is a controlled precursor chemical.

[0009] The second method for preparing aromatic ketone compounds is to use benzoate and benzyl cyanide as raw materials and sodium alkoxide as base to carry out Claisen condensation reaction to prepare the target compound (Chemical Reagents 27.012 (2005): 759-760.), with a reaction yield of 92%. The reaction formula is as follows:

[0010]

[0011] The raw material used in this method, benzyl cyanide, particularly aromatic-substituted benzyl cyanide, is difficult to prepare and expensive. Furthermore, the HBr used in the cyanohydrolysis and decarboxylation is highly corrosive, and a large amount of highly toxic HBr gas escapes during the reaction, posing a significant risk to the operator and the environment.

[0012] The third method for preparing aromatic ketone compounds uses benzoyl chloride and benzyl cyanide as raw materials, reacts with triethylamine to obtain β-ketonitrile, then hydrolyzes with sulfuric acid to obtain aromatic ketone, and finally recrystallizes and purifies with an organic solvent to obtain the target compound (CN103435464B). The total yield of the three steps is over 90%. The reaction formula is as follows:

[0013]

[0014] This method also uses benzyl cyanide as a raw material, and also uses corrosive and irritating reagents such as triethylamine, sulfuric acid, and acetic acid. The resulting acidic and alkaline wastewater is difficult to treat and is highly corrosive to equipment.

[0015] The fourth method for preparing aromatic ketone compounds uses styrene compounds as raw materials, hydrogen peroxide or tert-butyl hydroperoxide as an oxidant, palladium acetate as a catalyst, and an inorganic acid as a co-catalyst to prepare the target compound (CN107344904B). The reaction yield is 47%-87%. The reaction formula is as follows:

[0016]

[0017] The method uses hydrogen peroxide as an oxidant, which poses a safety hazard, and also uses palladium acetate as an expensive catalyst.

[0018] The fifth method for preparing aromatic ketone compounds is to use 1,2-diphenyl-1-ol as the raw material and PCC as the oxidant to oxidize the target compound (Bioorganic Chemistry 84(2019):276-284.), with a reaction yield of 95-99%. The reaction formula is as follows:

[0019]

[0020] The oxidant PCC used in this method is toxic, and the solvent dichloromethane used has a low boiling point and is volatile, thus causing great harm to the human body. Summary of the Invention

[0021] The first object of the present invention is to provide a method for preparing an aromatic ketone compound 1. The method uses an epoxy carboxylic acid compound 2 or a salt 3 thereof as a raw material, and obtains the aromatic ketone compound 1 by decarboxylation rearrangement under the condition of a Lewis acid as a catalyst. The aromatic ketone compound 1 is expressed as follows:

[0022]

[0023] in,

[0024] R 1 、R 2are independently any one of hydrogen, unsubstituted or substituted C1-C10 alkyl, unsubstituted or substituted C3-C10 cycloalkyl, unsubstituted or substituted C6-C12 aryl, and unsubstituted or substituted heteroaryl;

[0025] When R 1 、R 2 When it is an unsubstituted or substituted C1-C10 alkyl group, it is preferably a methyl group or an ethyl group;

[0026] When R 1 、R 2 When it is an unsubstituted C6-C12 aryl group, it is preferably a phenyl group;

[0027] When R 1 、R 2 When it is an unsubstituted or substituted heteroaryl group, it is preferably any one of heteroaryl groups containing 1 to 4 atoms selected from nitrogen, oxygen, and sulfur atoms, and more preferably an unsubstituted or substituted pyridyl group;

[0028] Ar is any one of an unsubstituted or substituted C6-C12 aryl group, an unsubstituted or substituted heteroaryl group containing 1-4 atoms selected from nitrogen, oxygen, and sulfur atoms;

[0029] Preferably, Ar is phenyl or Any of the following;

[0030] When Ar is n is an integer from 1 to 5, such as 1, 2, 3, 4, 5; when n is an integer not less than 2, multiple R 3 Can be the same or different;

[0031] R 3 is one or more selected from halogen, cyano, nitro, unsubstituted or substituted alkyl, unsubstituted or substituted alkoxy, and unsubstituted or substituted amino; preferably one or more selected from unsubstituted or substituted C1-C10 alkyl, and unsubstituted or substituted C1-C10 alkoxy;

[0032] More preferably, n is 1; R 3 Any one or more of halogen-substituted C1-C10 alkoxy groups, wherein the halogen group is F, Cl, Br, or I;

[0033] The M is an ammonium ion, an alkali metal ion, or an alkaline earth metal ion;

[0034] When M is an ammonium ion or an alkali metal ion, m is 1;

[0035] When M is an alkaline earth metal ion, m is 2;

[0036] The ammonium ion can be

[0037] R 4 -R 7 Each of them is independently H, unsubstituted or substituted C1-C10 alkyl, unsubstituted or substituted C3-C10 cycloalkyl, unsubstituted or substituted heterocycloalkyl containing nitrogen, oxygen and sulfur atoms, or unsubstituted or substituted C6-C12 aryl;

[0038] Y can be any of C, N, O, and S;

[0039] p is any integer between 0 and 2, such as 0, 1, 2;

[0040] The ammonium ion is When

[0041] The ammonium ion is When

[0042] When M is an alkali metal ion, it is preferably a sodium ion;

[0043] When M is an alkaline earth metal ion, it is preferably a calcium ion;

[0044] The above-mentioned ammonium ions are unsubstituted or substituted ammonium ions.

[0045] The Lewis acid can be AlCl3, FeCl3, SbCl5, SnCl4, BCl3, TiCl4, ZnCl2, MgCl2; preferably FeCl3, AlCl3, MgCl2;

[0046] The molar ratio of the raw material epoxy carboxylic acid compound 2 or its salt 3 to the catalyst 1 is 1:0.01-1, preferably 1:0.01-0.2;

[0047] The reaction solvent may be a polar solvent, a non-polar solvent or a mixture thereof, preferably one or more of a C6-C12 aromatic hydrocarbon solvent, a C1-C10 alcohol solvent, a C1-C6 amide solvent or a C1-C6 (sulfoxide) solvent;

[0048] The C6-C12 aromatic hydrocarbon solvents include toluene, xylene, and trimethylbenzene;

[0049] The C1-C10 alcohol solvents include methanol, ethanol, n-propanol, isopropanol, butanol, octanol, ethylene glycol, propylene glycol, glycerol, etc.

[0050] The C1-C6 amide solvents are specifically DMF, DMAC, and NMP;

[0051] The C1-C6 (oxy)sulfone solvents are specifically DMSO and sulfolane;

[0052] The second object of the present invention is to provide an epoxy carboxylic acid compound 2 or its salt 3, the structural formula of which is as follows:

[0053]

[0054] Among them, R 1 、R 2 , Ar, M, m are as defined above;

[0055] The third object of the present invention is to provide a method for preparing an epoxy carboxylic acid compound 2 or a salt thereof 3, the method comprising the following steps:

[0056] Step 1: α-substituted ester 4 reacts with carbonyl compound 5 in the presence of base 1 to give intermediate 6;

[0057] Step 2: hydrolyzing the intermediate 6 under the action of base 2 to obtain epoxy carboxylic acid compound 2; or further comprising

[0058] Step 3: epoxycarboxylic acid compound 2 is reacted with base 3 to obtain epoxycarboxylate 3;

[0059] The equation is as follows:

[0060]

[0061] R is an unsubstituted or substituted C1-C10 alkyl group; preferably a methyl group or an ethyl group;

[0062] L is halogen, OR 8 , R 8 It can be a sulfonyl group, a phosphonyl group; a sulfonyl group such as methanesulfonyl, p-toluenesulfonyl, etc.; a phosphonyl group such as (diethoxy)phosphonyl (Dimethyl)phosphono wait;

[0063] R 1 、R 2 , Ar, M, m are as defined above;

[0064] In the first step, the base 1 is an alkali metal or alkaline earth metal hydroxide, an alkali metal or alkaline earth metal carbonate, an alkali metal or alkaline earth metal alcoholate, an alkali metal or alkaline earth metal hydride, and a mixture thereof; preferably an alkali metal alcoholate, such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, and potassium tert-butoxide;

[0065] In the second step reaction, the base 2 is an alkali metal or alkaline earth metal hydroxide, an alkali metal or alkaline earth metal carbonate, preferably an alkali metal hydroxide, such as potassium hydroxide, sodium hydroxide, more preferably sodium hydroxide;

[0066] In the third step reaction, the base 3 is an organic base or an inorganic base; the organic base is an amine compound, specifically triethylamine, cyclohexanediamine, pyridine, tetrahydropyrrole, hexahydropyridine, morpholine, triethylenediammonium (DABCO), diazabicyclo (DBU); the inorganic base is ammonia gas, ammonia water, alkali metal or alkaline earth metal hydroxide, alkali metal or alkaline earth metal carbonate, preferably sodium hydroxide or calcium hydroxide;

[0067] The preparation of epoxy carboxylic acid compound 2 can be prepared step by step from compound 4 or in a one-pot process, that is, after obtaining intermediate 6, the product can be isolated and then hydrolyzed to prepare epoxy carboxylic acid compound 2. Alternatively, the product can be directly hydrolyzed to prepare epoxy carboxylic acid compound 2 without isolation, as represented by the following equation:

[0068]

[0069] R 1 、R 2 , Ar, R, L, base 1, and base 2 are as defined above.

[0070] The above-mentioned reactions can be carried out in an organic solvent, water or a mixture thereof, or in the absence of a solvent.

[0071] The first step reaction solvent is preferably an aromatic hydrocarbon solvent, an amide solvent, a (sub)sulfone solvent, or an alcohol solvent; the aromatic hydrocarbon solvent is preferably a C6-C12 aromatic hydrocarbon solvent, such as toluene, xylene, and trimethylbenzene; the amide solvent is preferably a C1-C6 amide solvent, such as DMF and DMAC; the (sub)sulfone solvent is preferably a C1-C6 (sub)sulfone solvent, such as DMSO and sulfolane; the alcohol solvent is preferably a C1-C10 alcohol solvent, such as methanol, ethanol, n-propanol, isopropanol, butanol, octanol, ethylene glycol, propylene glycol, glycerol, etc.

[0072] The solvent for the second step reaction is preferably an aromatic hydrocarbon solvent, an amide solvent, a (sub)sulfone solvent, or an alcohol solvent; the aromatic hydrocarbon solvent is preferably a C6-C12 aromatic hydrocarbon solvent, such as toluene, xylene, and trimethylbenzene; the amide solvent is preferably a C1-C6 amide solvent, such as DMF and DMAC; the (sub)sulfone solvent is preferably a C1-C6 (sub)sulfone solvent, such as DMSO and sulfolane; the alcohol solvent is preferably a C1-C10 alcohol solvent, such as methanol, ethanol, n-propanol, isopropanol, butanol, octanol, ethylene glycol, propylene glycol, glycerol, etc.;

[0073] The solvent for the third step reaction is water or an organic solvent; the organic solvent is preferably a C1-C10 solvent, more preferably n-hexane.

[0074] Compared with the prior art, the present invention has the following significant features:

[0075] (1) The present invention provides a new method for preparing aromatic ketone compounds, which avoids the use of toxic and harmful reagents such as PCl3, SOCl2, HBr, hydrogen peroxide, PCC, etc. used in the prior art;

[0076] (2) The method for preparing aromatic ketone compounds provided by the present invention uses cheap and readily available raw materials and Lewis acid as catalysts, has mild reaction conditions, avoids the use of highly corrosive reagents used in the prior art, does not require special equipment, and is suitable for industrial production.

[0077] (3) The method for preparing aromatic ketone compounds provided by the present invention has wide applicability and is suitable for preparing various substituted aromatic ketone compounds. DETAILED DESCRIPTION

[0078] Example 1: Synthesis of ethyl 2-phenyl-3-(3-pyridine)oxirane-2-carboxylate

[0079] DMF, ethyl α-chlorophenylacetate (122.5 g, 97%), and pyridine-3-carboxaldehyde (64.2 g) were added sequentially to a reaction flask, cooled to -5-0°C, and sodium ethoxide (53.0 g) was added portionwise. After the reaction of the raw materials was complete, toluene and water were added, followed by dropwise addition of concentrated hydrochloric acid (102 g, 30%). The layers were separated, and the organic phase was concentrated to yield 149.4 g of ethyl 2-phenyl-3-(3-pyridine)oxirane-2-carboxylate in an 87% yield. 1 H NMR (500MHz, DMSO): δ8.35 (dd, J=4.8, 1.6Hz, 1H), 8.32 (d, J=2.1Hz, 1H), 7.36 (dt, J=8.0, 1.9Hz, 1H), 7.31 –7.21(m,5H),7.15(dd,J=7.9,4.8Hz,1H),4.81(s,1H),4.20(qd,J=7.1,3.7Hz,2H),1.20(t,J=7.1Hz,3H).

[0080] Example 2: Synthesis of methyl 2-phenyl-2-methanesulfonyloxyacetate

[0081] Dichloromethane, methyl mandelate (85.6 g, 97%), and triethylamine (101 g) were added sequentially to a reaction flask, cooled to 0°C, and a mixed solution of methanesulfonyl chloride (114 g) and dichloromethane (160 g) was added dropwise. After the reaction of the raw materials was complete, saturated sodium chloride solution was added. The layers were separated, and the organic phase was dried, filtered, and concentrated to obtain 125.8 g of methyl 2-phenyl-2-methanesulfonyloxyacetate (98% yield).

[0082] Example 3: Synthesis of methyl 2-phenyl-3-(3-pyridine)oxirane-2-carboxylate

[0083] DMF, methyl 2-phenyl-2-methanesulfonyloxyacetate (125.8 g, 95%), and pyridine-3-carboxaldehyde (52.4 g) were added sequentially to a reaction flask, cooled to -5-0°C, and sodium methoxide (34.4 g) was added portionwise. After the reaction of the raw materials was complete, toluene and water were added, followed by dropwise addition of concentrated hydrochloric acid (83.5 g, 30%). The layers were separated, and the organic phase was concentrated to obtain 111.5 g of methyl 2-phenyl-3-(3-pyridine)oxirane-2-carboxylate, with a yield of 83%. 1 H NMR (500MHz, DMSO): δ8.65 (d, J=2.1Hz, 1H), 8.58 (dd, J=4.8, 1.6Hz, 1H), 7.76 (dt, J=7. 9,1.9Hz,1H),7.57(dt,J=4.4,2.4Hz,2H),7.51–7.39(m,4H),4.66(s,1H),3.51(s,3H).

[0084] Example 4: Synthesis of 2-phenyl-3-ethyloxirane-2-carboxylic acid ethyl ester

[0085] DMF, ethyl α-chlorophenylacetate (122.5 g, 97%), and propionaldehyde (34.8 g) were added sequentially to a reaction flask, cooled to -5-0°C, and sodium ethoxide (53.0 g) was added portionwise. After the reaction of the raw materials was complete, toluene and water were added, followed by dropwise addition of concentrated hydrochloric acid (102 g, 30%). The layers were separated, and the organic phase was concentrated to yield 120.6 g of ethyl 2-phenyl-3-ethyloxirane-2-carboxylate (85% yield). 1 H NMR (500MHz, DMSO): δ7.52–7.28(m,5H),4.14(qd,J=7.1,2.7Hz,2H),3.48(t, J=6.2Hz,1H),1.17(t,J=7.1Hz,3H),1.14–1.07(m,2H),0.86(t,J=7.5Hz,3H).

[0086] Example 5: Synthesis of 2,3-diphenyloxirane-2-carboxylic acid

[0087] Methyl 2-chloro-2-phenylacetate (184g), benzaldehyde (126g), and DMF were added sequentially to a reaction flask, cooled to -5-0°C, and sodium methoxide (69.5g) was added portionwise. After the reaction was complete, 30% aqueous sodium hydroxide solution (238g) was added dropwise, and the temperature was raised to 20-50°C. After the reaction was complete, the mixture was acidified, extracted, and concentrated to obtain 237.6g of the product, 2,3-diphenyloxirane-2-carboxylic acid, with a yield of 98%. 1H NMR (500MHz, DMSO) δ: 7.95 (s, 1H), 7.30–7.17 (m, 5H), 7.14 (dd, J = 5.0, 2.0Hz, 3H), 7.04 (dd, J = 6.4, 3.0Hz, 2H), 4.64 (s, 1H).

[0088] Example 6: Synthesis of 2-phenyl-3-(3-pyridine)oxirane-2-carboxylic acid

[0089] To ethanol and ethyl 2-phenyl-3-(3-pyridine)oxirane-2-carboxylate (149.4 g, 94%), 30% aqueous sodium hydroxide solution (83.5 g) was added dropwise. The temperature was raised to 20-50°C and the reaction was continued until the starting material disappeared. The mixture was concentrated, toluene and water were added, and hydrochloric acid (82.6 g, 30%) was added dropwise. The layers were separated, and the organic phase was concentrated to obtain 124.5 g of 2-phenyl-3-(3-pyridine)oxirane-2-carboxylic acid in a yield of 95%. 1 H NMR (500MHz, DMSO): δ8.34(s,1H),8.32(s,1H),7.95(s,1H),7.36(d,J=7.9Hz ,1H),7.24(dt,J=11.5,5.8Hz,5H),7.15(dd,J=7.5,4.8Hz,1H),4.76(s,1H).

[0090] Example 7: Synthesis of 2-phenyl-3-(3-pyridine)oxirane-2-carboxylic acid

[0091] To ethanol and methyl 2-phenyl-3-(3-pyridine)oxirane-2-carboxylate (111.5 g, 93%), 30% aqueous sodium hydroxide solution (65.1 g) was added dropwise, and the temperature was raised to 20-50°C to react until the starting material disappeared. The mixture was concentrated, toluene and water were added, and hydrochloric acid (64.4 g, 30%) was added dropwise. The layers were separated, and the organic phase was concentrated to obtain 96.0 g of the product, 2-phenyl-3-(3-pyridine)oxirane-2-carboxylic acid, in a yield of 92%.

[0092] Example 8: Synthesis of 2-phenyl-3-ethyloxirane-2-carboxylic acid

[0093] To ethanol and ethyl 2-phenyl-3-ethyloxirane-2-carboxylate (120.6 g, 93%), 30% aqueous sodium hydroxide solution (81.6 g) was added dropwise, and the temperature was raised to 20-50°C until the starting material disappeared. The mixture was concentrated, toluene and water were added, and hydrochloric acid (80.7 g, 30%) was added dropwise. The layers were separated, and the organic phase was concentrated to obtain 96.7 g of 2-phenyl-3-ethyloxirane-2-carboxylic acid, a yield of 94%.

[0094] Example 9: Synthesis of 2-phenyl-3-(3-pyridine)oxirane-2-carboxylic acid dicyclohexylamine salt

[0095] 2-Phenyl-3-(3-pyridine)oxirane-2-carboxylic acid (94%, 79.3 g) was added to n-hexane, stirred, and dicyclohexylamine (84.0 g, 0.46 mol) was added dropwise. The mixture was stirred at room temperature for 1 hour. The solid was precipitated and filtered. The filter cake was rinsed with 50 g of n-hexane and dried to obtain 132.2 g of the product 2-phenyl-3-(3-pyridine)oxirane-2-carboxylic acid dicyclohexylamine salt in a yield of 95%.

[0096] Example 10: Synthesis of 1-phenyl-2-(3-pyridyl)ethanone

[0097] DMF and magnesium chloride (4.3 g) were added to a reaction flask, and the temperature was raised to reflux. 2-Phenyl-3-(3-pyridyl)oxirane-2-carboxylic acid dicyclohexylamine salt (94%, 127 g) was added portionwise. After the addition was complete, the reaction was refluxed. After the reaction was complete, the solvent was removed by concentration, and the mixture was extracted, dried, and concentrated to obtain 52.8 g of the product, 1-phenyl-2-(3-pyridyl)ethanone, with a yield of 91%.

[0098] Example 11: Synthesis of 1-phenyl-2-(3-pyridine)ethanone

[0099] DMF and magnesium chloride (3.7 g) were added to a reaction flask, heated to reflux, and a mixed solution of 2-phenyl-3-(3-pyridine)oxirane-2-carboxylic acid (124.5 g, 96%) and DMF (100 g) was added dropwise. The reaction was continued until the starting material disappeared, followed by extraction, drying, and concentration to obtain 96.7 g of the product, 1-phenyl-2-(3-pyridine)ethanone, with a yield of 97%. 1 H NMR (500MHz, DMSO) δ8.53–8.42(m,2H),8.12–8.03(m,2H),7.78–7.63(m,2H),7.57(dd,J=10.6,4.8Hz,2H),7.37(dd,J=7.8,4.8Hz,1H),4.51(s,2H).

[0100] Example 12: Synthesis of Butyrophenone

[0101] DMF and aluminum chloride (4.1 g) were added to a reaction flask, heated to reflux, and a mixed solution of 2-phenyl-3-ethyloxirane-2-carboxylic acid (96.7 g, 95%) and DMF (80 g) was added dropwise. The reaction was continued until the starting material disappeared, followed by extraction, drying, and concentration to obtain 69.4 g of butyrophenone (96% yield). 1H NMR (500MHz, DMSO): δ7.96 (dd, J=5.2, 3.3Hz, 2H), 7.71–7.58 (m, 1H), 7.52 (dd, J=10 .6, 4.8Hz, 2H), 3.00 (t, J = 7.1Hz, 2H), 1.64 (h, J = 7.3Hz, 2H), 0.93 (t, J = 7.4Hz, 3H).

[0102] Example 13: Synthesis of 1,2-diphenylacetone

[0103] Add DMF and ferric chloride (17.1 g) to a reaction flask, raise the temperature to reflux, and dropwise add a mixed solution of 2,3-diphenyloxirane-2-carboxylic acid (237.6 g) and DMF (250 g). After the addition is complete, incubate the mixture. Continue the reaction until the starting material disappears, extract, dry, and concentrate to obtain 190 g of 1,2-diphenylacetone (98% yield). 1 H NMR (500MHz, DMSO): δ8.09–8.01(m,2H),7.68–7.60(m,1H),7.57–7.45(m,2H),7.35–7.19(m,5H),4.40(s,2H).

Claims

1. A method for preparing an aromatic ketone compound 1, characterized in that: Epoxycarboxylic acid compound 2 or its salt 3 undergoes decarboxylation rearrangement in the presence of a Lewis acid catalyst to give aromatic ketone compound 1, which is represented by the following equation: Among them, R 1 、R 2 are independently any one of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, and pyridyl; Ar is C6-C12 aryl, pyridine, Any of the following; n is an integer from 1 to 5. When n is an integer not less than 2, multiple R 3 Can be the same or different; R 3 is one or more of halogen, cyano, nitro, alkyl, alkoxy, and amino; M is an ammonium ion, an alkali metal ion, or an alkaline earth metal ion; When M is an ammonium ion or an alkali metal ion, m is 1; When M is an alkaline earth metal ion, m is 2; The ammonium ion is R 4 -R 7 are independently H, C1-C10 alkyl, C3-C10 cycloalkyl, or C6-C12 aryl; Y can be any one of C, N, O, and S; p is any integer from 0 to 2; The Lewis acid is AlCl3, FeCl3, or MgCl2.

2. The method according to claim 1, characterized in that The R 1 、R 2 is methyl, ethyl, phenyl, pyridyl; Ar is phenyl.

3. The method according to claim 2, characterized in that The R 1 、R 2 is methyl, ethyl, phenyl; ammonium ion is 4. The method according to claim 1, wherein The preparation method of the epoxy carboxylic acid compound 2 or its salt 3 comprises the following steps: Step 1: α-substituted ester 4 reacts with carbonyl compound 5 in the presence of base 1 to give intermediate 6; Step 2: Intermediate 6 is hydrolyzed and acidified under the action of base 2 to obtain epoxy carboxylic acid compound 2; or further comprising Step 3: Epoxycarboxylic acid compound 2 is reacted with base 3 to obtain epoxycarboxylate 3; the formula is as follows: in, R 1 、R 2 , Ar, M, m are defined as in claim 1; R is C1-C10 alkyl; L is halogen, OR 8 ; R 8 It is a sulfonyl group or a phosphonyl group.

5. The method according to claim 4, characterized in that The R is methyl or ethyl; R 8 is methanesulfonyl, p-toluenesulfonyl, (diethoxy)phosphonyl, (dimethyl)phosphonyl; base 1 is alkali metal or alkaline earth metal hydroxide, alkali metal or alkaline earth metal carbonate, alkali metal or alkaline earth metal alcoholate, alkali metal or alkaline earth metal hydride and a mixture thereof; base 2 is alkali metal or alkaline earth metal hydroxide, alkali metal or alkaline earth metal carbonate; base 3 is an organic base or an inorganic base, and when base 3 is an organic base, it is triethylamine, cyclohexanediamine, pyridine, tetrahydropyrrole, hexahydropyridine, morpholine, triethylenediammonium, or diazabicycle; when base 3 is an inorganic base, it is ammonia gas, ammonia water, alkali metal or alkaline earth metal hydroxide, or alkali metal or alkaline earth metal carbonate.

6. The method according to claim 5, characterized in that The base 1 is an alkali metal alcoholate; the base 2 is an alkali metal hydroxide.

7. The method according to claim 6, characterized in that Epoxycarboxylic acid compound 2 is prepared from intermediate 4 in one pot, as shown in the following equation: R 1 、R 2 , Ar, R, L, base 1, and base 2 are as described in claim 6.

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