CN110590597A - Preparation method of aryltriazene compound - Google Patents
Preparation method of aryltriazene compound Download PDFInfo
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- CN110590597A CN110590597A CN201910911587.4A CN201910911587A CN110590597A CN 110590597 A CN110590597 A CN 110590597A CN 201910911587 A CN201910911587 A CN 201910911587A CN 110590597 A CN110590597 A CN 110590597A
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/22—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond containing chains of three or more nitrogen atoms with one or more nitrogen-to-nitrogen double bonds
- C07C245/24—Chains of only three nitrogen atoms, e.g. diazoamines
Abstract
A preparation method of an aryltriazene compound belongs to the technical field of organic synthesis. The preparation method of the aryl triazene compound, namely 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene, comprises the following steps: substituted aniline raw material is diazotized under the action of sodium nitrite under the acidic condition, then, another substituted aniline is added under the alkaline condition for reaction, TLC (thin layer chromatography) is used for monitoring until the reaction is finished, and reaction liquid is separated and purified to prepare the aryl triazene compound. By adopting the technology, the invention adopts cheap and easily available substituted aniline as the raw material to synthesize the 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene, and the method has mild reaction conditions, low raw material price and good industrial prospect.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of an aryl triazene compound, namely 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene.
Background
Triazenes are organic compounds containing a structural unit of 3 nitrogen atoms in the molecule-N-, and are also referred to as diazoamino-based compounds. The molecular structure of the compound has 3 conjugated nitrogen atoms, so that the compound shows unique physical and chemical properties. The research on triazenes dates back to the 19 th century that Griess reported the synthesis of triazenes for the first time in 1862, and the compounds are gradually widely applied to industries such as medicines, dyes, food additives and the like.
Aryltriazenes are widely used in protecting groups for natural product synthesis, combinatorial chemistry, synthesis of polymers and oligomers, synthesis of heterocycles, and research of anticancer activity.
For example, the application of aryl triazenes in organic synthesis is researched by Shang Bo et al, Zhejiang university.
For example, CN 102424657 a describes novel triazenes for the treatment of cancer.
At present, a plurality of preparation methods for triazene compounds exist, for example, in 2010, Nahkai, a. et al report that aryl azide compounds react with grignard reagents and form triazene compounds with stable configuration through 1, 3 proton transfer; 2011 Wangyang et al adds a certain amount of concentrated hydrochloric acid into an ethanol solution of an amine compound, performs full protonation at room temperature, slowly drops an aqueous solution of sodium nitrite at-10 ℃, adds an ethanol solution of secondary amine and a sodium carbonate solid after diazotization reaction is complete, and obtains a triazene compound after reaction for a period of time; the aryl azide and a Grignard reagent or an organic lithium reagent react to prepare the aryl triazene, but the aryl triazene and the Grignard reagent have certain problems, such as high price of the catalyst, difficult recovery and the like.
Disclosure of Invention
In view of the above problems in the prior art, the present invention aims to provide a method for preparing aryltriazene compounds, i.e., 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene, wherein the aryltriazene compounds are synthesized by controlling a series of reaction sequences and reaction conditions, and the method has the advantages of mild conditions, low raw material cost and good industrial prospects.
The preparation method of the aryltriazene compound is characterized by comprising the following steps:
1) dropwise adding a certain amount of sodium nitrite aqueous solution into a 3, 4-dichloroaniline solution shown in the formula (I) at the temperature of-5 ℃ under an acidic condition, and carrying out heat preservation and stirring reaction for 1-3h after dropwise adding to obtain a 3, 4-dichloroaniline diazonium salt solution;
2) slowly dripping the 3, 4-dichloroaniline diazonium salt obtained in the step 1) into an alkaline solution within 30min under the ice-water bath condition, and continuously stirring for 5-30min to obtain a 3, 4-dichloroaniline diazonium salt solution shown in a formula (II);
3) adding the 3, 4-dichloroaniline diazoate solution shown in the formula (II) obtained in the step 2) into preheated para-fluoroaniline shown in the formula (III), reacting for 0.5-3h at 60-80 ℃ to generate a coupling product, and after the reaction is finished, carrying out post-treatment on the reaction solution to obtain 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene shown in the formula (IV), wherein the reaction equation is as follows:
the preparation method of the 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triaza-1-ene is characterized in that the acid used in the acidic condition in the step 1) is one or a mixture of sulfuric acid, hydrochloric acid or phosphoric acid, and hydrochloric acid is preferred.
The preparation method of the 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene is characterized in that the alkali in the alkaline solution in the step 1) is one or a mixture of sodium hydroxide, potassium hydroxide and sodium ethoxide, and preferably sodium hydroxide.
The preparation method of the aryltriazene compound is characterized in that the molar ratio of the 3, 4-dichloroaniline to the alkali shown in the step 2) is 1: 4 to 8.
The preparation method of the aryltriazene compound is characterized in that the feeding molar ratio of the 3, 4-dichloroaniline to the sodium nitrite in the step 1) is 1: 1-1.3, and preferably 1: 1.05.
The preparation method of the aryltriazene compound is characterized in that the reaction temperature is controlled to be-5 ℃ and preferably 0-5 ℃ when the sodium nitrite is added in the step 1).
The preparation method of the aryltriazene compound is characterized in that the preheating temperature of the para-fluoroaniline shown in the formula (III) in the step 3) is 60-80 ℃, and preferably 65-75 ℃.
The preparation method of the aryltriazene compound is characterized in that the post-treatment process of the reaction liquid in the step 3) is as follows: and cooling the reaction liquid to room temperature, adding ethyl acetate for extraction, separating an organic phase, adding water for washing for 2-3 times, carrying out pressure concentration on the organic phase to remove the solvent, and carrying out column chromatography separation on the obtained concentrate to obtain the target product 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene.
The preparation method of the aryltriazene compound is characterized in that an eluant for column chromatography separation is petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 4-8: 1, preferably 6: 1.
The invention has the beneficial effects that: the method has mild reaction conditions and low raw material price, is suitable for industrial production, and the 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene provided by the invention is widely applied to industries such as medicines, dyes, food additives and the like as an aryl triazene compound.
Detailed Description
The present invention is further illustrated by the following examples, but the scope of the invention is not limited thereto.
Example 1 (influence of the temperature of the diazotization Process on the yield)
Adding 1.36g (0.01mmol) of 3, 4-dichloroaniline and 1mL of distilled water into a 50mL flask, heating to 75 ℃, dropwise adding 5.5mL of concentrated hydrochloric acid with the mass fraction of 36% after the 3, 4-dichloroaniline and 1mL of distilled water are dissolved, adding 5mL of distilled water after vigorous stirring, heating and intermittently stirring until the mixture is completely dissolved, naturally cooling to room temperature, adding 15mL of water, stirring to form uniform white milky suspension, placing the flask into an ice water bath at the temperature of-5 ℃, dropwise adding a sodium nitrite aqueous solution (5mL, 0.0105mol and 2.1M), and continuously stirring for 2 hours to obtain a 3, 4-dichloroaniline diazonium salt aqueous solution.
Adding a sodium hydroxide aqueous solution (15mL, 0.06mol, 4M) into a 100mL beaker, carrying out ice-water bath, slowly dropwise adding a 3, 4-dichloroaniline diazonium salt solution within 30min under a vigorous stirring condition when the temperature of the solution is reduced to-5 ℃, and continuously stirring for 5min in the ice-water bath after dropwise adding is finished to obtain the 3, 4-dichloroaniline diazonium salt aqueous solution.
Weighing 11.1g (0.1mol) of para-fluoroaniline in a 100mL beaker, stirring vigorously and heating to 70 ℃, dropwise adding the 3, 4-dichlorobenzenediazonium salt aqueous solution, stirring at constant temperature for 40min after the dropwise adding is finished, monitoring by TLC until the reaction is finished, and stopping the reaction. The reaction solution is extracted by ethyl acetate, desolventizing is carried out, and the concentrated solution is separated by column chromatography (petroleum ether/ethyl acetate is 6:1, V/V) to obtain yellow powder, namely the product 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene. The above reaction formula is as follows:
process for preparing 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triaz-1-ene1H NMR was as follows:
1H NMR(500MHz，DMSO-d6)δ12.90(s，1H)，8.27–7.05(m，7H)。
influence of temperature in the epidiazotization Process on the yield
| Reaction temperature/. degree.C | Yield/%) |
| -5 | 53 |
| 0 | 53 |
| 5 | 50 |
Example 2 (influence of molar ratio of substituted Aniline to sodium nitrite on yield)
Adding 1.36g (0.01mol) of 3, 4-dichloroaniline and 1mL of distilled water into a 50mL flask, heating to 75 ℃, dropwise adding 5.5mL of concentrated hydrochloric acid with the mass fraction of 36% after dissolving, adding 5mL of distilled water after vigorous stirring, heating and intermittently stirring until the mixture is completely dissolved, naturally cooling to room temperature, adding 15mL of water, stirring to form uniform white emulsion suspension, placing the flask into an ice water bath at 0-5 ℃, repeating the experiment for three times, and dropwise adding 5.0mL, 5.7mL and 6.2mL of 2.1M sodium nitrite aqueous solution (namely the sodium nitrite substances are 0.0105, 0.012 and 0.013mol respectively), and continuously stirring for 2h to obtain three parts of 3, 4-dichloroaniline diazonium salt aqueous solutions with the numbers of a, b and c;
taking three 100mL beakers, respectively adding sodium hydroxide aqueous solutions (15mL, 0.06mol, 4M), carrying out ice-water bath, when the temperature of the solution is reduced to 0-5 ℃, slowly dropwise adding the aqueous solutions a, b and c in 30min under a vigorous stirring condition, and continuously stirring in the ice-water bath for 5min after dropwise adding is finished to obtain three parts of 3, 4-dichloroaniline diazonium salt aqueous solutions, wherein the three parts are numbered as a ', b ' and c ';
weighing three parts of 11.1g (0.1mmol) of para-fluoroaniline into three 100mL beakers, respectively dropwise adding the aqueous solutions a ', b ' and c ' when the mixture is vigorously stirred and heated to 70 ℃, stirring at constant temperature for 40min after the dropwise addition is finished, monitoring by TLC until the reaction is finished, and stopping the reaction. The reaction solution is extracted by ethyl acetate, desolventizing is carried out, and the concentrated solution is separated by column chromatography (petroleum ether/ethyl acetate is 6:1, V/V) to obtain yellow powder, namely the product 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene.
The above reaction formula is as follows:
process for preparing 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triaz-1-ene1H NMR was as follows:
1H NMR(500MHz，DMSO-d6)δ12.90(s，1H)，8.27–7.05(m，7H)。
TABLE Effect of molar ratio of substituted anilines to sodium nitrite on yield
Example 3 influence of preheating temperature of reactant (III) on yield
Adding 1.36g (0.01mmol) of 3, 4-dichloroaniline and 1mL of distilled water into a 50mL flask, heating to 75 ℃, dropwise adding 5.5mL of concentrated hydrochloric acid with the mass fraction of 36% after the 3, 4-dichloroaniline and 1mL of distilled water are dissolved, adding 5mL of distilled water after vigorous stirring, heating and intermittently stirring until the mixture is completely dissolved, naturally cooling to room temperature, adding 15mL of water, stirring to form uniform white milky suspension, placing the flask into an ice water bath at 0-5 ℃, dropwise adding an aqueous solution of sodium nitrite (5mL, 0.0105mol and 2.1M), and continuously stirring for 2 hours to obtain an aqueous solution of 3, 4-dichloroaniline diazonium salt.
Adding a sodium hydroxide aqueous solution (15mL, 0.06mol, 4M) into a 100mL beaker, carrying out ice-water bath, slowly dropwise adding a 3, 4-dichloroaniline diazonium salt solution within 30min under the condition of vigorous stirring when the temperature of the solution is reduced to 0-5 ℃, and continuously stirring for 5min in the ice-water bath after dropwise adding is finished to obtain the 3, 4-dichloroaniline diazonium salt aqueous solution.
Weighing 11.1g (0.1mol) of para-fluoroaniline in a 100mL beaker, stirring vigorously and heating to 60-80 ℃, dropwise adding the 3, 4-dichlorobenzenediazonium salt aqueous solution, stirring at constant temperature for 40min after the dropwise addition is completed, monitoring by TLC until the reaction is finished, and stopping the reaction. The reaction solution is extracted by ethyl acetate, desolventizing is carried out, and the concentrated solution is separated by column chromatography (petroleum ether/ethyl acetate is 6:1, V/V) to obtain yellow powder, namely the product 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene. The above reaction formula is as follows:
process for preparing 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triaz-1-ene1H NMR was as follows:
1H NMR(500MHz，DMSO-d6)δ12.90(s，1H)，8.27–7.05(m，7H)。
influence of preheating temperature of the Epimedium reactant (III) on the yield
| Reaction temperature/. degree.C | Yield/%) |
| 60 | 48 |
| 70 | 53 |
| 80 | 45 |
Example 4 influence of molar ratio of substituted Aniline to base on yield
Adding 1.36g (0.01mmol) of 3, 4-dichloroaniline and 1mL of distilled water into a 50mL flask, heating to 75 ℃, dropwise adding 5.5mL of 36% concentrated hydrochloric acid after dissolving, adding 5mL of distilled water after vigorous stirring, heating and intermittently stirring until completely dissolving, naturally cooling to room temperature, adding 15mL of water, stirring to form uniform white emulsion suspension, placing the flask into an ice water bath at 0-5 ℃, dropwise adding a sodium nitrite aqueous solution (5mL, 0.0105mol, 2.1M), continuously stirring for 2h, and repeating the experiment for three times to obtain three parts of 3, 4-dichloroaniline diazonium salt aqueous solutions.
Respectively adding 10mL, 15mL and 20mL of 4M potassium hydroxide aqueous solution into 3 different 100mL beakers, carrying out ice-water bath, when the temperature of the solution is reduced to 0-5 ℃, respectively and slowly dripping the 3, 4-dichloroaniline diazonium salt aqueous solution in 30min under the condition of vigorous stirring, and continuously stirring in the ice-water bath for 5min after dripping is finished to obtain the 3, 4-dichloroaniline diazonium salt aqueous solution, wherein the numbers are d, e and f.
Weighing three parts of 11.1g (0.1mol) para-fluoroaniline into three 100mL beakers, respectively dropwise adding the d, e and f aqueous solutions when vigorously stirring and heating to 70 ℃, stirring at constant temperature for 40min after finishing dropwise adding, monitoring by TLC until the reaction is finished, and stopping the reaction. The reaction solution is extracted by ethyl acetate, desolventizing is carried out, and the concentrated solution is separated by column chromatography (petroleum ether/ethyl acetate is 6:1, V/V) to obtain yellow powder, namely the product 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene. The above reaction formula is as follows:
process for preparing 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triaz-1-ene1H NMR was as follows:
1H NMR(500MHz，DMSO-d6)δ12.90(s，1H)，8.27–7.05(m，7H)。
effect of the molar ratio of Epotrisubstituted Anilines to bases on yield
The description is given for the sole purpose of illustrating embodiments of the inventive concept and should not be taken as limiting the scope of the invention to the particular forms set forth in the embodiments, but rather as being limited only to the equivalents thereof as may be contemplated by those skilled in the art based on the teachings herein.
Claims (9)
1. A preparation method of an aryltriazene compound is characterized by comprising the following steps:
1) under the acidic condition, dropwise adding a certain amount of sodium nitrite aqueous solution into a 3, 4-dichloroaniline solution shown in the formula (I) at the temperature of-5 ~ 5 ℃, and carrying out heat preservation and stirring reaction for 1-3h after dropwise adding to obtain a 3, 4-dichloroaniline diazonium salt solution;
2) slowly dripping the 3, 4-dichloroaniline diazonium salt obtained in the step 1) into an alkaline solution within 30min under the ice-water bath condition, and continuously stirring for 5-30min to obtain a 3, 4-dichloroaniline diazonium salt solution shown in a formula (II);
3) adding the 3, 4-dichloroaniline diazoate solution shown in the formula (II) obtained in the step 2) into preheated para-fluoroaniline shown in the formula (III), reacting at 60 ~ 80 ℃ for 0.5-3h to generate a coupling product, and after the reaction is finished, carrying out post-treatment on the reaction solution to obtain 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) trinitron-1-ene shown in the formula (IV), wherein the reaction equation is as follows:
。
2. the method for preparing aryltriazenes according to claim 1, wherein the acid used in the acidic condition in step 1) is one or more of sulfuric acid, hydrochloric acid or phosphoric acid, preferably hydrochloric acid.
3. The method for preparing aryltriazenes according to claim 1, wherein the alkali in the alkaline solution in step 1) is one or more of sodium hydroxide, potassium hydroxide and sodium ethoxide, preferably sodium hydroxide.
4. The process for producing aryltriazenes according to claim 1, wherein the molar ratio of 3, 4-dichloroaniline to base in step 2) is 1: 4 ~ 8.
5. The method for preparing aryltriazenes according to claim 1, characterized in that the molar ratio of 3, 4-dichloroaniline to sodium nitrite in step 1) is 1:1 ~ 1.3.3, preferably 1: 1.05.
6. The method for preparing aryltriazenes according to claim 1, wherein the reaction temperature is controlled to-5 ~ 5 ℃, preferably 0 ~ 5 ℃ when adding sodium nitrite in step 1).
7. The process for producing aryltriazenes according to claim 1, wherein the preheat temperature of para-fluoroaniline of formula (III) in step 3) is 60 ~ 80 ℃, preferably 65 ~ 75 ℃.
8. The preparation method of the aryltriazenes compound according to claim 1, characterized in that the post-treatment process of the reaction liquid in the step 3) is that the reaction liquid is cooled to room temperature, ethyl acetate is added for extraction, then the organic phase is separated, water is added for washing for 2 ~ 3 times, the organic phase is decompressed and concentrated to remove the solvent, and the obtained concentrate is separated by column chromatography to obtain the target product 1- (3, 4-dichlorophenyl) -3- (4-fluorophenyl) triazo-1-ene.
9. The method for preparing aryltriazenes according to claim 8, wherein the eluent for column chromatography is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 4 ~ 8:1, preferably 6: 1.
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| CN116218097A (en) * | 2022-09-07 | 2023-06-06 | 海啊科技股份有限公司 | PVC material capable of controlling temperature to foam and preparation method and application thereof |
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