CN114507156A - Preparation method of cyanophenyl compound - Google Patents
Preparation method of cyanophenyl compound Download PDFInfo
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- CN114507156A CN114507156A CN202111233765.6A CN202111233765A CN114507156A CN 114507156 A CN114507156 A CN 114507156A CN 202111233765 A CN202111233765 A CN 202111233765A CN 114507156 A CN114507156 A CN 114507156A
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- C07C253/00—Preparation of carboxylic acid nitriles
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Abstract
The invention discloses a preparation method of a cyanophenyl compound, which comprises the following steps: in an organic solvent, in the presence of fluoride salt, nitrobenzene compounds shown in the formula I and a cyanation reagent are subjected to the following reaction to prepare benzonitrile compounds shown in the formula II. The preparation method takes nitrobenzene compounds as starting raw materials to prepare the benzonitrile compounds through one-step reaction, and has simple post-treatment and high yield.
Description
Technical Field
The invention relates to a preparation method of a cyanophenyl compound.
Background
The cyanophenyl compound is an aromatic compound containing a cyano functional group, and the cyano functional group is very important in organic synthesis reaction, can be hydrolyzed to prepare carboxyl and reduced into amino, and can be converted into other functional groups. As an important fine chemical raw material and a synthetic intermediate, a benzonitrile compound can be used for preparing dyes, perfumes, pesticides, medicines and the like, and a synthetic method thereof is always valued.
The cyanophenyl compound is produced mainly by ammoxidation, halogeno-benzene cyanation, diazotization, aldoxime dehydration, amide dehydration, etc. The ammoxidation method for synthesizing the cyanophenyl compound has higher requirements on the catalyst and high cost of the catalyst. The method for synthesizing the cyanophenyl compound by the halogenated benzene cyanidation method uses heavy metal cyanide as a cyanation reagent, so that the three wastes are seriously polluted, and the post-treatment cost is higher. The diazotization cyanogen method for synthesizing the cyanophenyl compound has the disadvantages of complex and dangerous process and large discharge amount of three wastes. The yield of the benzonitrile compound synthesized by the aldoxime dehydration method and the amide dehydration method is not high, or expensive catalysts are used, so the production cost is high.
Disclosure of Invention
The invention aims to solve the technical problems of high preparation and production cost, serious three-waste pollution, difficult post-treatment and the like of the existing cyanophenyl compound, and provides a preparation method of the cyanophenyl compound. The preparation method takes nitrobenzene compounds as starting raw materials to prepare the benzonitrile compounds through one-step reaction, and has simple post-treatment and high yield.
The invention provides a preparation method of a cyanophenyl compound, which comprises the following steps: in an organic solvent, in the presence of fluoride salt, reacting nitrobenzene compounds shown in a formula I with a cyanation reagent as shown in the specification to prepare benzonitrile compounds shown in a formula II;
wherein R is an electron-withdrawing substituent.
In one embodiment of the invention, R is-NO2、-F、-CF3or-CN, e.g. -CF3or-NO2。
In one embodiment of the invention, R is in the ortho, para or meta position, preferably ortho or para, relative to the nitro group.
The position of R relative to nitro group in the compound shown in formula I is correspondingly the position of R relative to cyano group in the compound shown in formula II.
In one embodiment of the present invention, the organic solvent is an aprotic polar solvent. The aprotic polar solvent can be one or more of a ketone solvent, an ether solvent, an amide solvent and a sulfone solvent. The ketone solvent is preferably acetone. The ethereal solvent is preferably tetrahydrofuran. The amide solvent is preferably one or more of N, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, and hexamethylphosphoramide, for example, N-dimethylformamide. The sulfone solvent is preferably dimethyl sulfoxide and/or sulfolane.
In one embodiment of the present invention, the cation of the fluoride salt is a monovalent cation. The monovalent cation may be an alkali metal ion or-N (R)a)4 +Wherein R isaIs C1～C6An alkyl group.
In one embodiment of the present invention, the fluoride salt is one or more of sodium fluoride, potassium fluoride, cesium fluoride, tetramethylammonium fluoride and tetrabutylammonium fluoride, such as tetrabutylammonium fluoride and/or potassium fluoride.
In one embodiment of the present invention, the cyanation reagent is sodium cyanide or potassium cyanide.
In a certain embodiment of the invention, the molar volume ratio of the compound represented by formula I to the organic solvent is 1 to 3mol/L, for example, 2 to 2.9mol/L, and for example, 2.5 mol/L.
In a certain embodiment of the invention, the molar ratio of the fluorinated salt to the compound represented by formula I is 0.02-0.5: 1, for example 0.1-0.2: 1.
In one embodiment of the invention, the molar ratio of the cyanation reagent to the compound represented by formula I is 1.0-2.0: 1, for example, 1.0-1.5: 1.
In one embodiment of the invention, the reaction temperature of the reaction is from 25 ℃ to 250 ℃, such as from 60 ℃ to 190 ℃, for example, also 100 ℃.
In one embodiment of the present invention, the reaction is carried out under anhydrous conditions.
The reaction temperature is related to the activity of the compound shown as the formula I and the catalyst fluoride salt, and the reaction temperature is lower when the activity of the substrate and the catalyst is high, and vice versa.
In one embodiment of the present invention, R is-CF3or-NO2(ii) a The organic solvent is N, N-dimethylformamide or dimethyl sulfoxide; the fluoride salt is potassium fluoride or tetrabutylammonium fluoride; the cyanation reagent is cyanationPotassium; the molar volume ratio of the compound shown in the formula I to the organic solvent is 2-2.9 mol/L; the molar ratio of the fluoride salt to the compound shown in the formula I is 0.1-0.2: 1; the mol ratio of the cyanation reagent to the compound shown in the formula I is 1.0-1.5: 1; the reaction temperature of the reaction is 60-190 ℃.
The preparation method can also further comprise a post-treatment step. The post-treatment step comprises filtration, and the filtrate is distilled under reduced pressure; or the post-treatment step comprises filtering, pouring the filtrate into water, and performing suction filtration.
The above preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention without departing from the common general knowledge in the art.
The reagents and starting materials used in the present invention are commercially available.
The positive progress effects of the invention are as follows: compared with the existing synthesis route that the nitrobenzene compounds are firstly hydrogenated and reduced into aniline compounds, then diazotized and halogenated, and finally cyanated by using a cyanation reagent for 3-4 steps, the synthesis route is shortened, the reaction yield is improved, the discharge amount of three wastes is reduced, and the post-treatment is simple.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
In the following examples, DMF represents N, N-dimethylformamide; DMSO denotes dimethyl sulfoxide.
Example 1
Adding ortho-nitrobenzotrifluoride (19.1g,0.100mol), potassium cyanide (7.2g,0.115mol), tetrabutylammonium fluoride (2.7g,0.010mol) and 40mL of solvent DMF into a reaction flask, heating to 100 ℃, keeping the temperature for reaction for 6h, cooling to room temperature after the reaction is finished, filtering to remove generated potassium nitrite and unreacted potassium cyanide, recovering DMF from filtrate, and evaporating the product under reduced pressure to obtain 15.1g of anhydrous oily liquid ortho-trifluoromethylbenzonitrile, with the purity of 99.7% and the yield of 88.3%.
The prepared product was analyzed by LC comparison with a standard compound (purchased o-trifluoromethylbenzonitrile) and the retention time of both was consistent and was 4.208 min.
The LC analysis method was as follows:
| item | Parameter(s) |
| Chromatographic column | ZORBAX Eclopse XDB-C18(4.6mm*250mm*5μm) |
| Column temperature/. degree.C | 35 |
| Mobile phase | Water methanol 30:70(v/v) |
| Flow rate/(mL/min) | 1.0mL/min |
| Sample size/. mu.L | 1 |
| Detection wavelength/nm | 254 |
| Detection time/min | 13 |
Example 2
Adding ortho-nitrobenzotrifluoride (19.1g,0.100mol), potassium cyanide (7.5g,0.115mol), anhydrous potassium fluoride (1.0g,0.017mol) and 50mL solvent DMSO into a reaction flask, heating to 190 ℃, carrying out heat preservation reaction for 10h, cooling to room temperature after the reaction is finished, filtering to remove generated potassium nitrite, catalyst potassium fluoride and unreacted potassium cyanide, recovering DMSO from filtrate, and carrying out reduced pressure evaporation to obtain an anhydrous oily liquid ortho-trifluoromethylbenzonitrile of 14.8g, the purity of 99.3% and the yield of 86.5%.
The prepared product was analyzed by LC comparison with a standard compound (purchased o-trifluoromethylbenzonitrile) and the retention time of both was consistent and was 4.208 min.
The LC analysis method was the same as that in example 1.
Example 3
Adding p-dinitrobenzene (16.8g,0.100mol), potassium cyanide (6.6g,0.101mol), tetrabutylammonium fluoride (4.3g,0.016mol) and 35mL of DMF (solvent) into a reaction flask, heating to 60 ℃, keeping the temperature for reaction for 1h, cooling to room temperature after the reaction is finished, filtering to remove the generated potassium nitrite and unreacted potassium cyanide, pouring the filtrate into 500mL of water, performing suction filtration, washing a filter cake with water, and drying to obtain 13.9g of light yellow solid p-nitrobenzonitrile with the purity of 99.8 percent and the yield of 93.9 percent.
The product of the preparation was analyzed by LC comparison with a standard compound (purchased p-nitrobenzonitrile) and the retention time was consistent at 3.946 min.
The LC analysis method was the same as that in example 1.
Example 4
Adding o-dinitrobenzene (16.8g,0.100mol), potassium cyanide (6.9g,0.106mol), tetrabutylammonium fluoride (3.4g,0.013mol) and 35mL of DMSO solvent into a reaction flask, heating to 60 ℃, keeping the temperature for reaction for 1h, cooling to room temperature after the reaction is finished, filtering to remove the generated potassium nitrite and unreacted potassium cyanide, pouring the filtrate into 500mL of water, performing suction filtration, washing a filter cake with water, and drying to obtain 13.3g of light yellow solid o-nitrobenzonitrile with the purity of 99.4% and the yield of 89.9%.
The prepared product and a standard compound (purchased o-nitrobenzonitrile) are subjected to LC comparative analysis, and the retention time of the product and the standard compound is consistent and is 3.785 min.
The LC analysis method was the same as that in example 1.
Claims (10)
1. A method for preparing a benzonitrile compound, characterized in that it comprises the steps of: in an organic solvent, in the presence of fluoride salt, reacting nitrobenzene compounds shown in a formula I with a cyanation reagent as shown in the specification to prepare benzonitrile compounds shown in a formula II;
wherein R is an electron-withdrawing substituent.
2. The method of claim 1, wherein R satisfies one or more of the following conditions:
condition 1, R is-NO2、-F、-CF3or-CN, preferably-CF3or-NO2；
With the proviso 2, R is located at the ortho-, para-or meta-position, preferably the ortho-or para-position, of the nitro group.
3. The method according to claim 1, wherein the organic solvent is an aprotic polar solvent; the aprotic polar solvent can be one or more of a ketone solvent, an ether solvent, an amide solvent and a sulfone solvent; the ketone solvent is preferably acetone; the ether solvent is preferably tetrahydrofuran; the amide solvent is preferably one or more of N, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone and hexamethylphosphoramide; the sulfone solvent is preferably dimethyl sulfoxide and/or sulfolane.
4. The method of claim 1, wherein the cation of the fluoride salt is a monovalent cation; preferably, theThe monovalent cation is an alkali metal ion or-N (R)a)4 +Wherein R isaIs C1～C6An alkyl group; the fluoride salt may be one or more of sodium fluoride, potassium fluoride, cesium fluoride, tetramethylammonium fluoride and tetrabutylammonium fluoride, such as tetrabutylammonium fluoride and/or potassium fluoride.
5. The method of claim 1, wherein the cyanating agent is sodium cyanide or potassium cyanide.
6. The method according to claim 1, wherein the molar volume ratio of the compound of formula I to the organic solvent is 1 to 3mol/L, such as 2 to 2.9mol/L, and such as 2.5 mol/L.
7. The method of claim 1, wherein the molar ratio of the fluoride salt to the compound of formula I is 0.02 to 0.5:1, such as 0.1 to 0.2: 1.
8. The method of claim 1, wherein the molar ratio of the cyanating agent to the compound of formula I is 1.0-2.0: 1, such as 1.0-1.5: 1.
9. The method of claim 1, wherein the reaction is carried out at a reaction temperature of from 25 ℃ to 250 ℃, such as from 60 ℃ to 190 ℃, and further such as 100 ℃.
10. The method of claim 1, wherein R is-CF3or-NO2(ii) a The organic solvent is N, N-dimethylformamide or dimethyl sulfoxide; the fluoride salt is potassium fluoride or tetrabutylammonium fluoride; the cyanation reagent is potassium cyanide; the molar volume ratio of the compound shown in the formula I to the organic solvent is 2-2.9 mol/L; the molar ratio of the fluoride salt to the compound shown in the formula I is 0.1-0.2: 1; the cyanogenThe molar ratio of the base reagent to the compound shown in the formula I is 1.0-1.5: 1; the reaction temperature of the reaction is 60-190 ℃.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2134900A (en) * | 1983-02-15 | 1984-08-22 | Ici Plc | Process for the preparation of cyanotetrachlorobenzenes |
| ES2179727A1 (en) * | 2000-03-01 | 2003-01-16 | Univ Barcelona | Preparation of nitro aromatic oxidized derivatives involves treatment with nucleophilic reagents for electrochemical oxidation |
| CN109574877A (en) * | 2018-12-30 | 2019-04-05 | 南京正荣医药化学有限公司 | A kind of preparation method of 2- cyano -3- fluoride trifluoro toluene |
-
2021
- 2021-10-22 CN CN202111233765.6A patent/CN114507156A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2134900A (en) * | 1983-02-15 | 1984-08-22 | Ici Plc | Process for the preparation of cyanotetrachlorobenzenes |
| ES2179727A1 (en) * | 2000-03-01 | 2003-01-16 | Univ Barcelona | Preparation of nitro aromatic oxidized derivatives involves treatment with nucleophilic reagents for electrochemical oxidation |
| CN109574877A (en) * | 2018-12-30 | 2019-04-05 | 南京正荣医药化学有限公司 | A kind of preparation method of 2- cyano -3- fluoride trifluoro toluene |
Non-Patent Citations (1)
| Title |
|---|
| ILUMINADA GALLARDO，等: "Nucleophilic Aromatic Substitution for Heteroatoms: An Oxidative Electrochemical Approach", 《J. ORG. CHEM》, vol. 67, pages 2548 - 2555, XP055362358, DOI: 10.1021/jo010847t * |
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