CN112142587A - Benzoetonic acid and preparation method and application thereof - Google Patents
Benzoetonic acid and preparation method and application thereof Download PDFInfo
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- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
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- C07C59/185—Saturated compounds having only one carboxyl group and containing keto groups
- C07C59/205—Saturated compounds having only one carboxyl group and containing keto groups containing rings
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- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention relates to a ketonic acid and a preparation method and application thereof, wherein the method comprises the following steps: carrying out hydrolysis reaction on phenylacetonitrile oxime shown in a formula (I) under the catalysis of inorganic acid to obtain phenylacetic acid shown in a formula (II); the preparation method for preparing the acetophenone acid has the advantages of high yield, high product purity, simple operation, environmental protection and no pollution. The acetophenone acid is used as a fine chemical synthesis intermediate.
Description
Technical Field
The invention relates to the technical field of fine chemical engineering, in particular to acetophenone acid, a preparation method and application thereof.
Background
The acetophenone acid compound is a common fine chemical synthesis intermediate, o-methyl acetophenone acid is an intermediate for synthesizing novel bactericides kresoxim-methyl and trifloxystrobin, acetophenone acid is an intermediate for synthesizing triazinone herbicides such as metamitron, phenazine and the like, and the acetophenone acid compound is an intermediate for synthesizing medical oxybenzonium bromide and chiral mandelic acid.
US5221762 uses o-methylbenzoic acid as raw material, and refluxing with thionyl chloride to obtain o-methylbenzoyl chloride, and then reacting with sodium cyanide to obtain o-methylbenzoyl cyanide, and hydrolyzing to obtain o-methyl acetophenone acid. The method generates more three wastes, and cyanide is needed in the reaction process, so that the risk is higher.
US4596885 uses benzoyl cyanide as a raw material and phenylacetic acid is obtained by hydrolysis with hydrochloric acid, which is relatively simple, but benzoyl cyanide is relatively expensive and the overall process cost is relatively high due to the relatively low process yield, and is not suitable for industrial production.
CN108503545A discloses a method for preparing phenylacetate by catalytic oxidation of mandelate, which comprises using oxygen-containing gas as oxidant, using vanadium oxide and transition metal nitrate as composite catalyst, and subjecting mandelate to one-step oxidation at 30-150 deg.C under mild reaction condition to obtain phenylacetate. In the method, the metal oxide is used as a catalyst, so that the method can cause pollution to the environment and is not environment-friendly.
Therefore, there is a need in the art to develop a method for preparing acetophenone acid, which has high yield and purity, is easy to operate, and is free from pollution.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide the preparation method of the acetophenone acid, which has the advantages of simple process, convenient operation, short reaction time, high yield and high product purity.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a preparation method of acetophenone acid, which comprises the following steps:
carrying out hydrolysis reaction on phenylacetonitrile oxime shown in a formula (I) under the catalysis of inorganic acid, and purifying to obtain phenylacetic acid shown in a formula (II);
and R is selected from any one of a hydrogen atom, halogen and alkyl.
The invention prepares the phenylacetic acid by carrying out hydrolysis reaction on the phenylacetonitrile oxime under the catalysis of the independent inorganic acid, can effectively improve the yield and the product purity, and has the advantages of simple steps, convenient operation, environmental protection and no pollution.
The drawing of the single bond crossing the benzene ring in the formula (I) and the formula (II) represents that the R group can be connected at any position of the benzene ring, and the reaction general formula of different R substitution positions is as follows:
preferably, the mass ratio of the inorganic acid to the phenylacetonitrile oxime is 1-10:1, such as 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, and the like.
The invention prepares the phenylacetic acid by catalyzing the phenylacetonitrile oxime to carry out hydrolysis reaction by using the single inorganic acid, and simultaneously controls the specific addition amount of the inorganic acid, and the reason is that 1:1 accords with the theoretical acid for hydrolysis, but the sulfuric acid needs 5eq to have better effect during the actual reaction, and the hydrochloric acid needs 10eq to have relatively better result; the method has a certain relation with the concentration of acid ions (from the final result, the reaction effect of sulfuric acid is better than that of hydrochloric acid), and finally the high-purity high-yield acetophenone acid is obtained, and the method has simple steps and convenient operation.
Too high content of inorganic acid can lead to more waste acid, difficult three-waste treatment, and too low content can lead to incomplete hydrolysis and lower yield and content.
Preferably, the halogen includes any one of a chlorine atom, a bromine atom and a fluorine atom.
Preferably, the alkyl group is a C1-C5 alkyl group, preferably any one of methyl, ethyl, isopropyl and tert-butyl.
Preferably, the inorganic acid comprises hydrochloric acid and/or sulfuric acid, preferably sulfuric acid.
Preferably, the inorganic acid has a mass concentration of 20 to 98%, for example 21%, 25%, 30%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, etc., preferably 60 to 90%.
Preferably, the temperature of the hydrolysis reaction is 60 to 150 ℃, such as 62 ℃, 65 ℃, 68 ℃, 70 ℃, 75 ℃, 80 ℃, 85 ℃, 90 ℃, 95 ℃, 100 ℃, 110 ℃, 120 ℃, 130 ℃, 140 ℃, 145 ℃ and the like, preferably 80 to 120 ℃.
Preferably, the time of the hydrolysis reaction is 1-24h, such as 2h, 3h, 5h, 10h, 15h, 20h, 22h, 24h, etc., preferably 3-12 h.
Preferably, the method further comprises: purifying the product of the hydrolysis reaction.
Preferably, the method of purification comprises extraction.
Preferably, the extractant for extraction comprises aromatic hydrocarbon and/or halogenated alkane, preferably any one or at least two of dichloromethane, dichloroethane and toluene.
Preferably, the extraction specifically comprises the steps of:
adding an extracting agent into the product of the hydrolysis reaction, stirring for the first time, stirring for the second time in an ice bath, and filtering to obtain white crystals, namely the acetophenone acid shown in the formula (II).
Preferably, the preparation method specifically comprises the following steps:
carrying out hydrolysis reaction on phenylacetonitrile oxime shown in a formula (I) for 1-24h at the temperature of 60-150 ℃ under the catalysis of inorganic acid with the mass concentration of 20-98%, adding an extracting agent into a product of the hydrolysis reaction, carrying out primary stirring, carrying out secondary stirring in an ice bath, and filtering to obtain white crystals, namely the phenylacetic acid shown in the formula (II).
The second object of the present invention is to provide a phenylacetic acid produced by the method described in the first object.
The third purpose of the invention is to provide the application of the acetophenone acid in the second purpose, and the acetophenone acid is used for synthesizing bactericides, triazine ketone herbicides, medical oxybenzoic ammonium bromide or chiral mandelic acid.
Preferably, the triazinone herbicide comprises metamitron or phenazine.
Compared with the prior art, the invention has the following beneficial effects:
the method for preparing the acetophenone acid has the advantages of simple steps, convenient operation, short time consumption, high yield and high product purity.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
In the invention, the synthesis method of phenylacetonitrile oxime shown in formula (I) is the prior art, and exemplarily provides a synthesis method of p-methyl phenylacetonitrile oxime, which comprises the following specific steps:
a500 mL three-necked flask was charged with 65.5g of p-tolylacetonitrile (0.5mol), and 200mL of methanol was added thereto, and 27g of sodium methoxide (0.5mol) was slowly added thereto with stirring, followed by stirring for 0.5 h. Raising the temperature to 40 ℃, dropwise adding 112g (0.525mol) of tert-butyl nitrite, completing the dropwise adding within 1h, keeping for 3h after the dropwise adding, and removing the methanol under negative pressure. Adding 300mL of water to dissolve the kettle liquid after desolventizing, dropwise adding hydrochloric acid to neutralize, separating out solid, and stopping dripping hydrochloric acid when the pH value of the water liquid is 7. The reaction flask was transferred to an ice bath and stirred for 2h, filtered to give a yellow solid, which was dried to a total of 157.76g with a yield of 98.6%.
Product liquid chromatography/Mass Spectrometry (LC/MS) characterization, [ M + 1%]+(％)：161(100)。
1H-NMR(CDCl3，400MHz)：2.34(s，3H，CH3)，2.00(s，1H，OH)，7.42-7.97(4H，ArH)。
Example 1
Synthesizing o-methyl acetophenone acid:
adding 110g of 90% concentrated sulfuric acid (1.0mol) into a 500mL three-necked flask, heating to 100 ℃, dropwise adding 32g of o-tolylacetonitrile oxime (0.2mol) within 1h, heating to 120 ℃ after dropwise adding, maintaining for 5h, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection of no raw material. Adding 50mL of dichloroethane, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring for 2h under ice bath, filtering to obtain white-like crystals, and drying to obtain 32.51g of solid with the purity of 99.2% and the yield of 98.3%.
Product liquid chromatography/Mass Spectrometry (LC/MS) characterization, [ M + 1%]+(％)：165(100)。
1H-NMR(CDCl3，400MHz)：2.26(s，3H，CH3)，7.19-7.41(4H,ArH)，11.85(s，1H，OH)。
Example 2
Synthesizing o-methyl acetophenone acid:
33g of 60% concentrated sulfuric acid (0.2mol) is added into a 250mL three-necked flask, the temperature is increased to 80 ℃, 32g of o-tolylacetonitrile oxime (0.2mol) is added dropwise within 1h, and after the dropwise addition is finished, the reaction is stopped after maintaining for 12 h. Adding 50mL of toluene, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring again for 2h in ice bath, filtering to obtain yellow solid, and drying to obtain 31.34g of solid with the purity of 76.2% and the yield of 72.8%.
Product LC/MS characterization, [ M +1 ]]+(％)：165(100)。
1H-NMR(CDCl3，400MHz)：2.26(s，3H，CH3)，7.19-7.41(4H,ArH)，11.85(s，1H，OH)。
Example 3
Synthesis of m-methyl acetophenone acid:
adding 100g of 98% concentrated sulfuric acid (1.0mol) into a 500mL three-necked flask, heating to 100 ℃ under stirring, dropwise adding 32g of m-methyl phenylacetonitrile oxime (0.2mol) within 1h, heating to 120 ℃ after dropwise adding, maintaining for 5h, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection of no raw material. Adding 50mL of dichloromethane, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5, stirring for 2h in ice bath, filtering to obtain white-like crystals, and drying to obtain 32.79g of solid with the purity of 98.7% and the yield of 97.2%.
Product LC/MS characterization, [ M +1 ]]+(％)：165(100)。
1H-NMR(CDCl3，400MHz)：2.30(s，3H，CH3)，7.34-7.70(4H,ArH)，11.80(s，1H，OH)。
Example 4
Synthesis of p-methyl acetophenone acid:
adding 120g of 80% concentrated sulfuric acid (1.0mol) into a 500mL three-necked flask, heating to 100 ℃, dropwise adding 32g of p-methyl phenylacetonitrile oxime (0.2mol) within 1h, heating to 120 ℃ after dropwise adding, maintaining for 5h, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection of no raw material. Adding 50mL of toluene, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring for 2h under ice bath, filtering to obtain white-like crystals, and drying to obtain 31.72g of solid with the purity of 98.8% and the yield of 95.5%.
Product LC/MS characterization, [ M +1 ]]+(％)：165(100)。
1H-NMR(CDCl3，400MHz)：2.34(s，3H，CH3)，7.42-7.97(4H,ArH)，11.91(s，1H，OH)。
Example 5
Synthesis of acetophenone acid:
adding 120g of 80% concentrated sulfuric acid (1.0mol) into a 500mL three-necked flask, heating to 100 ℃, dropwise adding 29.5g of phenylacetonitrile oxime (0.2mol) within 1h, heating to 120 ℃ after dropwise adding, maintaining for 4h, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection of no raw material. Adding 50mL of toluene, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring for 2h in ice bath, filtering to obtain white-like crystals, and drying to obtain 29.55g of solid with the purity of 98.1% and the yield of 96.6%.
Product LC/MS characterization, [ M +1 ]]+(％)：151(100)。
1H-NMR(CDCl3，400MHz)：7.19-7.41(4H,ArH)，11.85(s，1H，OH)。
Example 6
Synthesis of p-ethyl-benzene-ethyl-ketone acid:
adding 120g of 80% concentrated sulfuric acid (1.0mol) into a 500mL three-necked flask, heating to 100 ℃, dropwise adding 35g of p-ethyl benzene acetonitrile oxime (0.2mol) within 1h, heating to 120 ℃ after dropwise adding, maintaining for 5h, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection of no raw material. Adding 50mL of dichloroethane, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring for 2h under ice bath, filtering to obtain off-white crystals, and drying to obtain 32.54g of solid with the purity of 98.3% and the yield of 89.9%.
Product LC/MS characterization, [ M +1 ]]+(％)：179(100)。
1H-NMR(CDCl3，400MHz)：1.25(d，2H，CH2)，2.60(s，3H，CH3)，7.01-7.64(4H,ArH)，11.85(s，1H，OH)。
Example 7
Synthesis of 4-tert-Butylphenylpyruvic acid:
adding 120g of 80% concentrated sulfuric acid (1.0mol) into a 500mL three-necked flask, heating to 100 ℃, dropwise adding 41g of 4-tert-butyl benzene acetonitrile oxime (0.2mol) within 1h, heating to 120 ℃ after dropwise adding, maintaining for 5h, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection of no raw material. Adding 50mL of dichloroethane, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring for 2h under ice bath, filtering to obtain white-like crystals, and drying to obtain 33.25g of solid with the purity of 98.5% and the yield of 79.5%.
Product LC/MS characterization, [ M +1 ]]+(％)：207(100)。
1H-NMR(CDCl3，400MHz)：1.35(s，9H，CH3)，7.01-7.64(4H,ArH)，11.85(s，1H，OH)。
Example 8
Synthesis of 4-isopropylphenyl-acetic acid:
adding 120g of 80% concentrated sulfuric acid (1.0mol) into a 500mL three-necked flask, heating to 100 ℃, dropwise adding 38g of 4-isopropyl-phenylacetonitrile oxime (0.2mol) within 1h, heating to 120 ℃ after dropwise adding, maintaining for 5h, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection of no raw material. Adding 50mL of dichloroethane, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring for 2h under ice bath, filtering to obtain white-like crystals, and drying to obtain 32.22g of solid with the purity of 98.8% and the yield of 83.0%.
Product LC/MS characterization, [ M +1 ]]+(％)：193(100)。
1H-NMR(CDCl3，400MHz)：1.25(s，6H，CH3)，7.01-7.64(4H,ArH)，11.85(s，1H，OH)。
Example 9
Synthesis of p-fluorophenylketonic acid:
adding 120g of 80% concentrated sulfuric acid (1.0mol) into a 500mL three-necked flask, heating to 100 ℃, dropwise adding 33g of p-fluorobenzyl acetonitrile oxime (0.2mol) within 1h, after dropwise adding, maintaining the temperature at 100 ℃ for 6h, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection does not use raw materials. Adding 50mL of dichloroethane, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring for 2h under ice bath, filtering to obtain white-like crystals, and drying to obtain 32.18g of solid with the purity of 98.9% and the yield of 94.7%.
Product LC/MS characterization, [ M +1 ]]+(％)：169(100)。
1H-NMR(CDCl3，400MHz)：7.01-7.64(4H,ArH)，11.85(s，1H，OH)。
Example 10
Synthesizing 4-bromobenzoic acid:
adding 120g of 80% concentrated sulfuric acid (1.0mol) into a 500mL three-necked flask, heating to 100 ℃, dropwise adding 45g of 4-bromobenzene acetonitrile oxime (0.2mol) within 1h, continuously maintaining for 6h after dropwise adding, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection of no raw material. Adding 50mL of dichloroethane, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring for 2h under ice bath, filtering to obtain yellow crystals, and drying to obtain 43.08g of solid with the purity of 98.0% and the yield of 92.6%.
Product LC/MS characterization, [ M +1 ]]+(％)：229(100)。
1H-NMR(CDCl3，400MHz)：7.01-7.64(4H,ArH)，11.85(s，1H，OH)。
Example 11
Synthesis of p-chloro-acetophenone acid:
adding 120g of 80% concentrated sulfuric acid (1.0mol) into a 500mL three-necked flask, heating to 100 ℃, dropwise adding 36g of p-chlorobenzonitrile oxime (0.2mol) within 1h, continuously maintaining for 7h after dropwise adding, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection does not have raw materials. Adding 50mL of dichloroethane, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring for 2h under ice bath, filtering to obtain light yellow solid, and drying to obtain 36.20g of solid with the purity of 97.8% and the yield of 96.4%.
Product LC/MS characterization, [ M +1 ]]+(％)：185(100)。
1H-NMR(CDCl3，400MHz)：7.01-7.64(4H,ArH)，11.85(s，1H，OH)。
Example 12
Synthesizing o-methyl acetophenone acid:
adding 200g of 20% sulfuric acid (0.4mol) into a 500mL three-necked flask, heating to 100 ℃, dropwise adding 32g of o-tolylacetonitrile oxime (0.2mol) within 1h, heating to 150 ℃ after dropwise adding, maintaining for 10h, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection of no raw material. Adding 50mL of dichloroethane, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring for 2h under ice bath, filtering to obtain yellow solid, and drying to obtain 31.22g of solid with the purity of 86.5% and the yield of 82.3%.
Product liquid chromatography/Mass Spectrometry (LC/MS) characterization, [ M + 1%]+(％)：165(100)。
1H-NMR(CDCl3，400MHz)：2.26(s，3H，CH3)，7.19-7.41(4H,ArH)，11.85(s，1H，OH)。
Example 13
Synthesizing o-methyl acetophenone acid:
200g of 37% concentrated hydrochloric acid (2.0mol) is added into a 500mL three-necked flask, the temperature is raised to 100 ℃, 32g of o-tolylacetonitrile oxime (0.2mol) is dropwise added within 1h, after the dropwise addition is finished, the reaction is maintained for 1h, sampling is carried out, and the reaction is considered to be finished after HPLC detection shows that no raw material exists. Adding 50mL of toluene, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring again for 2h in ice bath, filtering to obtain light yellow crystals, and drying to obtain 34.24g of solid with the purity of 88.4% and the yield of 92.3%.
Product LC/MS characterization, [ M +1 ]]+(％)：165(100)。
1H-NMR(CDCl3，400MHz)：2.26(s，3H，CH3)，7.19-7.41(4H,ArH)，11.85(s，1H，OH)。
Example 14
Synthesizing o-methyl acetophenone acid:
100g of 37% concentrated hydrochloric acid (1.0mol) is added into a 500mL three-necked flask, the temperature is increased to 80 ℃, 32g of o-tolylacetonitrile oxime (0.2mol) is dropwise added within 1h, and after the dropwise addition is finished, the temperature is increased to 100 ℃ and maintained for 24h, and then the reaction is stopped. Adding 50mL of toluene, stirring for 0.5h, cooling to normal temperature, continuing to stir for 0.5h, stirring again for 2h in ice bath, filtering to obtain yellow solid, and drying to obtain 33.20g of solid with the purity of 83.4% and the yield of 84.4%.
Product LC/MS characterization, [ M +1 ]]+(％)：165(100)。
1H-NMR(CDCl3，400MHz)：2.26(s，3H，CH3)，7.19-7.41(4H,ArH)，11.85(s，1H，OH)。
Comparative example 1
Synthesizing o-methyl acetophenone acid:
500g of 37% concentrated hydrochloric acid (5.0mol) and 8.2g of o-tolylacetonitrile oxime (0.05mol) are added into a 1L three-necked flask, the temperature is raised to 90 ℃, after the maintenance for 8 hours, a sample is taken, and the reaction is considered to be finished (more impurities are shown on a normalization spectrum) after no raw material is detected by HPLC. Adding 50mL of toluene, stirring for 0.5h, cooling to normal temperature, stirring for 2h in ice bath, separating out a mud-like substance, filtering, drying, and obtaining the product with the purity of 72.4% and the yield of 38.5%.
Product LC/MS characterization, [ M +1 ]]+(％)：165(100)。
1H-NMR(CDCl3，400MHz)：2.26(s，3H，CH3)，7.19-7.41(4H,ArH)，11.85(s，1H，OH)。
Comparative example 2
Synthesizing o-methyl acetophenone acid:
adding 500g of 37% concentrated hydrochloric acid (5.0mol) and 8.2g of o-tolylacetonitrile oxime (0.05mol) into a 1L three-necked flask, heating to 90 ℃, stirring, dropwise adding 90g of acetic acid (1.5mol), continuing to maintain for 8 hours after dropwise adding, sampling, and determining that the reaction is finished (the more impurities are shown on a normalized spectrogram) after HPLC (high performance liquid chromatography) detects no raw materials). Adding 50mL of toluene, stirring for 0.5h, cooling to normal temperature, then no solid is separated out, stirring for 2h in ice bath, separating out a mud-like substance, filtering, drying, and obtaining the product with the purity of 66.5% and the yield of 28.5%.
Product LC/MS characterization, [ M +1 ]]+(％)：165(100)。
1H-NMR(CDCl3，400MHz)：2.26(s，3H，CH3)，7.19-7.41(4H,ArH)，11.85(s，1H，OH)。
Comparative example 3
Synthesizing o-methyl acetophenone acid:
adding 500g of 37% concentrated hydrochloric acid (5.0mol) and 8.2g of o-tolylacetonitrile oxime (0.05mol) into a 1L three-necked flask, heating to 90 ℃, stirring, dropwise adding 171g of trifluoroacetic acid (1.5mol), continuing maintaining for 6 hours after dropwise adding, sampling, and determining that the reaction is finished after HPLC (high performance liquid chromatography) detection of no raw material (the more impurities are shown on a normalized spectrogram). Adding 50mL of toluene, stirring for 0.5h, cooling to normal temperature, then no solid is separated out, stirring for 2h in ice bath, separating out a mud-like substance, filtering, drying, and obtaining the product with the purity of 59.9% and the yield of 24.4%.
Product LC/MS characterization, [ M +1 ]]+(％)：165(100)。
1H-NMR(CDCl3，400MHz)：2.26(s，3H，CH3)，7.19-7.41(4H,ArH)，11.85(s，1H，OH)。
The preparation methods of the acetophenone acid provided by the embodiments 1 to 14 have high yield and high product purity; in the comparative example 1, the molar ratio of the inorganic acid to the o-methyl phenylacetonitrile oxime is 100:1, the addition amount of the inorganic acid is too large, and the yield and the purity are both reduced; comparative examples 2 and 3, in which acetic acid or trifluoroacetic acid was additionally added, yield and product purity were greatly reduced, and thus it was confirmed that the addition of a separate inorganic acid catalyst was critical in the preparation method provided by the present invention, and the addition of trifluoroacetic acid or acetic acid inhibited the hydrolysis reaction, resulting in a decrease in purity and yield.
The results show that the phenylacetic acid is prepared by the hydrolysis reaction of the phenylacetonitrile oxime catalyzed by the single inorganic acid, the yield and the product purity can be effectively improved, and the method has the advantages of simple steps, convenience in operation, environmental friendliness and no pollution.
The present invention is illustrated in detail by the examples described above, but the present invention is not limited to the details described above, i.e., it is not intended that the present invention be implemented by relying on the details described above. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.
Claims (10)
1. A preparation method of acetophenone acid, which is characterized by comprising the following steps:
carrying out hydrolysis reaction on phenylacetonitrile oxime shown in a formula (I) under the catalysis of inorganic acid to obtain phenylacetic acid shown in a formula (II);
and R is selected from any one of a hydrogen atom, halogen and alkyl.
2. The production method according to claim 1, characterized in that the mass ratio of the inorganic acid to the phenylacetonitrile oxime is 1-10: 1;
preferably, the halogen includes any one of a chlorine atom, a bromine atom and a fluorine atom;
preferably, the alkyl group is a C1-C5 alkyl group, preferably any one of methyl, ethyl, isopropyl and tert-butyl.
3. The production method according to claim 1 or 2, characterized in that the inorganic acid comprises hydrochloric acid and/or sulfuric acid, preferably sulfuric acid;
preferably, the mass concentration of the inorganic acid is 20-98%, preferably 60-90%.
4. The method according to any one of claims 1 to 3, wherein the temperature of the hydrolysis reaction is 60 to 150 ℃, preferably 80 to 120 ℃.
5. The method according to any one of claims 1 to 4, wherein the hydrolysis reaction is carried out for a period of time of 1 to 24 hours, preferably 3 to 12 hours.
6. The method of any one of claims 1-5, further comprising: purifying the product of the hydrolysis reaction;
preferably, the method of purification comprises extraction.
7. The preparation method according to claim 6, wherein the extracted extractant comprises aromatic hydrocarbon and/or halogenated alkane, preferably any one or at least two of dichloromethane, dichloroethane and toluene.
8. The method according to claim 6 or 7, wherein the extraction comprises the following steps:
adding an extracting agent into the product of the hydrolysis reaction, stirring for the first time, stirring for the second time in an ice bath, and filtering to obtain white crystals, namely the acetophenone acid shown in the formula (II);
preferably, the preparation method specifically comprises the following steps:
carrying out hydrolysis reaction on phenylacetonitrile oxime shown in a formula (I) for 1-24h at the temperature of 60-150 ℃ under the catalysis of inorganic acid with the mass concentration of 20-98%, adding an extracting agent into a product of the hydrolysis reaction, carrying out primary stirring, carrying out secondary stirring in an ice bath, and filtering to obtain white crystals, namely the phenylacetic acid shown in the formula (II).
9. A phenylacetic acid prepared according to the method of any one of claims 1-8.
10. Use of a ketonic acid according to claim 9, characterized in that it is used for the synthesis of fungicides, triazinones herbicides, medicinal oxfennium bromide or chiral mandelic acid;
preferably, the triazinone herbicide comprises metamitron or phenazine.
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