CN109336762B - Synthesis method of diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate - Google Patents
Synthesis method of diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate Download PDFInfo
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Abstract
The invention discloses a method for synthesizing 2- (2, 6-diethyl-4-methylbenzene) diethyl malonate, which comprises the following steps: under the action of a catalyst, reacting 2, 6-diethyl-4-methylaniline with isoamyl nitrite to obtain 2, 6-diethyl-4-methylphenyl diazonium salt; reacting 2, 6-diethyl-4-methylphenyl diazonium salt with diethyl malonate under the alkaline condition to obtain diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate. The yield of the 2- (2, 6-diethyl-4-methylbenzene) diethyl malonate can reach about 85 percent, and the highest yield can reach 92 percent; the possibility of generating three wastes is greatly reduced by adopting a non-aqueous system. The method takes the isoamyl nitrite as a diazotization reagent, not only accelerates the reaction speed, but also compensates for low-temperature kinetic energy under the condition of the existence of a catalyst, the produced diazonium salt is relatively stable in a low-temperature and non-aqueous system, the decomposition is less, and the diazotization reaction yield is close to 100%.
Description
Technical Field
The invention belongs to the field of pesticide synthesis, and particularly relates to a synthesis method of diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate.
Background
Pinoxaden was developed by shinada corporation and marketed in 2006. Pinoxaden belongs to a new class of phenylpyrazoline herbicides and is an inhibitor of acetyl-coa carboxylase (ACC) which causes a hindrance in fatty acid synthesis, cessation of cell growth and division, destruction of lipid containing structures in cell membranes and death of weeds. The pinoxaden has systemic conductivity, is mainly used for cereals and preventing and removing gramineous weeds after germination, and the using amount of the effective components is 30-60 g/hm2。
The pinoxaden has the following structural formula:
chemical name: 8- (2, 6-diethyl-4-methylphenyl) -1,2,4, 5-tetrahydro-7-oxo-7H-pyrazolo [1,2-d][1,4,5]Oxygen and nitrogen-9-yl-2, 2-dimethylpropionate; CAS number: 243973-20-8.
Diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate is an intermediate for synthesizing pinoxaden, and the structural formula of the diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate is as follows:
chinese patent application (CN 106928253A) discloses a method for synthesizing 2- (2, 6-diethyl-4-methylbenzene) diethyl malonate, which comprises the steps of firstly, carrying out diazotization thermal decomposition on 2, 6-diethyl-4-methylaniline by using sodium nitrite to generate 2, 6-diethyl-4-methyl bromobenzene; in the presence of alkali, reacting 2, 6-diethyl-4-methyl bromide with diethyl malonate under the action of a catalyst to generate diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate; the catalyst is one of cuprous iodide, cuprous bromide or bis (triphenylphosphine) nickel chloride. In the method, the yield of diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate is low and is 60-78%. Meanwhile, when the 2, 6-diethyl-4-methyl bromobenzene is prepared, a hydrobromic acid solution is taken as a reaction solvent, a sodium nitrite aqueous solution is taken as a diazotization reagent, diazonium salt is unstable in a water-containing system, the reaction temperature is as high as 60-90 ℃, the diazonium salt is easily decomposed, excessive byproducts are generated, and the reaction liquid can be subjected to extraction, concentration and reduced pressure distillation to obtain pure 2, 6-diethyl-4-methyl bromobenzene to enter the next reaction; in addition, aqueous systems also lead to three wastes, which is not environmentally friendly.
Disclosure of Invention
The invention aims to provide a method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate.
The purpose of the invention is realized by the following technical scheme:
a synthetic method of diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate comprises the following steps:
the method comprises the following steps:
step (1), diazotization reaction: under the action of a catalyst, reacting 2, 6-diethyl-4-methylaniline with isoamyl nitrite to obtain 2, 6-diethyl-4-methylphenyl diazonium salt;
and (3) reacting the 2, 6-diethyl-4-methylphenyl diazonium salt with diethyl malonate under an alkaline condition to obtain diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate.
In the step (1), the molar ratio of the 2, 6-diethyl-4-methylaniline to the isoamyl nitrite is 1: 1-1.5, preferably 1: 1.05.
The reaction solvent is tetrahydrofuran, acetonitrile, N-dimethylformamide, acetone, 1, 2-dichloroethane, dichloromethane or toluene, preferably tetrahydrofuran or acetonitrile.
The catalyst is cuprous chloride, cupric chloride and cuprous iodide, preferably cuprous iodide. The amount of the catalyst is 0.5-3 wt%, preferably 0.8-1.5 wt% of the weight of the 2, 6-diethyl-4-methylaniline.
The reaction temperature is 0-35 ℃, preferably 5-10 ℃.
In the step (2), the molar ratio of diethyl malonate to 2, 6-diethyl-4-methylaniline is 1-1.5: 1, preferably 1.1: 1.
The alkali under the alkaline condition is one or more of sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, sodium hydroxide and potassium hydroxide, preferably sodium ethoxide, sodium hydride and potassium tert-butoxide, most preferably potassium tert-butoxide, the solubility and alkalinity of potassium tert-butoxide are moderate, and the yield of diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate can be ensured to reach at least 85%.
The molar ratio of the potassium tert-butoxide to the diethyl malonate is 0.9-1.3: 1, and the ratio is preferably 1: 1-1.3: 1, more preferably 1.1:1, in order to obtain a high reaction rate, reduce the generation of byproducts, and improve the yield.
The reaction solvent is N, N-dimethylformamide, acetone, acetonitrile, tetrahydrofuran, preferably N, N-dimethylformamide.
The reaction temperature is 10-60 ℃, preferably 15-20 ℃.
The synthesis method of the diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate specifically comprises the following steps:
mixing 2, 6-diethyl-4-methylaniline, a catalyst and a reaction solvent, dropwise adding isoamyl nitrite, controlling the temperature to be 0-35 ℃ and preferably 5-10 ℃ in the dropwise adding process, and after the dropwise adding is finished, carrying out heat preservation reaction for about 2 hours;
and (2) controlling the temperature to be 0-5 ℃, adding alkali into a mixed solution of diethyl malonate and a reaction solvent in batches, after the addition is finished, slowly heating to 10-60 ℃, preferably 15-20 ℃, reacting for 1 hour, then dropwise adding the diazonium solution prepared in the step (1), controlling the temperature to be 10-60 ℃, preferably 15-20 ℃, and after the dropwise addition is finished, carrying out heat preservation reaction.
As a further preferable embodiment of the method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate of the present invention, the method further comprises the steps of: adding water into the reaction solution obtained in the step (2) to quench the reaction, cooling to 0-5 ℃, and filtering to obtain a crude product; recrystallizing the crude product by using normal hexane to obtain a pure 2- (2, 6-diethyl-4-methylbenzene) diethyl malonate product; wherein, the specific operation of recrystallization is as follows: heating and dissolving the crude product by using n-hexane at 55-60 ℃, and cooling to 5-10 ℃ for crystallization.
The invention has the beneficial effects that:
the invention adopts a non-aqueous system, thereby greatly reducing the possibility of generating three wastes. The method takes the isoamyl nitrite as a diazotization reagent, not only accelerates the reaction speed, but also compensates for low-temperature kinetic energy under the condition of the existence of a catalyst, the produced diazonium salt is relatively stable in a low-temperature and non-aqueous system, the decomposition is less, and the diazotization reaction yield is close to 100%. The method for preparing 2- (2, 6-diethyl-4-methylbenzene) diethyl malonate has the yield of about 85 percent and the highest yield of 92 percent.
Detailed Description
The technical solution of the present invention will be further explained with reference to the specific embodiments.
Example 1
Adding 500g of acetonitrile into a four-neck flask, adding 163.3g (1mol) of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous chloride, cooling to 5-10 ℃, dropwise adding 123g (1.05mol) of isoamyl nitrite, controlling the temperature to be 5-10 ℃ in the dropwise adding process, after the dropwise adding is finished, carrying out heat preservation reaction for about 2 hours, and keeping the temperature of the diazo solution for later use after the reaction is finished.
And (2) adding 176g (1.1mol) of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 136g (1.2mol) of potassium tert-butoxide in batches, controlling the temperature to be 0-5 ℃, finishing feeding, slowly heating to 15-20 ℃, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution on the basis of no material flushing, controlling the temperature to be 15-20 ℃, after dropwise adding, preserving heat and reacting for 1.5 hours, and finishing the reaction. Adding the reaction solution into 1000g of water to quench the reaction, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product; adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 90.6 percent.
Example 2
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 136g of potassium tert-butoxide in batches, controlling the temperature to 0-5 ℃, slowly heating to 15-20 ℃ after feeding, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to 15-20 ℃, preserving the temperature and reacting for 1.5 hours after dropwise adding, and finishing the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 92 percent.
Example 3
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 2.4g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 136g of potassium tert-butoxide in batches, controlling the temperature to 0-5 ℃, slowly heating to 15-20 ℃ after feeding, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to 15-20 ℃, preserving the temperature and reacting for 1.5 hours after dropwise adding, and finishing the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely the yield of diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%): 91 percent.
Example 4
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.2g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 136g of potassium tert-butoxide in batches, controlling the temperature to 0-5 ℃, slowly heating to 15-20 ℃ after feeding, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to 15-20 ℃, preserving the temperature and reacting for 1.5 hours after dropwise adding, and finishing the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 88 percent.
Example 5
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 65.3g of sodium methoxide in batches, controlling the temperature to be 0-5 ℃, slowly heating to 15-20 ℃ after the addition is finished, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to be 15-20 ℃, preserving the temperature and reacting for 1.5 hours after the dropwise addition is finished, and finishing the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 78 percent.
Example 6
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 82.3g of sodium ethoxide in batches, controlling the temperature to 0-5 ℃, slowly heating to 15-20 ℃ after the addition is finished, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to 15-20 ℃, and after the dropwise addition is finished, preserving the heat and reacting for 1.5 hours to finish the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 82 percent.
Example 7
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 29g of sodium hydride in batches, controlling the temperature to 0-5 ℃, slowly heating to 15-20 ℃ after the addition is finished, reacting for 1 hour, dropwise adding the diazo liquid prepared in the step (1) into the reaction liquid, controlling the temperature to 15-20 ℃, and after the dropwise adding is finished, preserving heat and reacting for 1.5 hours, wherein the reaction is finished. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 85 percent.
Example 8
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 48.4g of sodium hydroxide in batches, controlling the temperature to 0-5 ℃, slowly heating to 15-20 ℃ after the addition is finished, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to 15-20 ℃, and after the dropwise addition is finished, preserving the heat and reacting for 1.5 hours to finish the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 70 percent.
Example 9
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 67.8g of potassium hydroxide in batches, controlling the temperature to 0-5 ℃, slowly heating to 15-20 ℃ after the addition is finished, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to 15-20 ℃, preserving the temperature and reacting for 1.5 hours after the dropwise addition is finished, and finishing the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 75 percent.
TABLE 1 Effect of different base classes on the yield
Example 10
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 124g of potassium tert-butoxide in batches, controlling the temperature to 0-5 ℃, slowly heating to 15-20 ℃ after feeding, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to 15-20 ℃, preserving the temperature and reacting for 1.5 hours after dropwise adding, and finishing the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 86 percent.
Example 11
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 160g of potassium tert-butoxide in batches, controlling the temperature to 0-5 ℃, slowly heating to 15-20 ℃ after feeding, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to 15-20 ℃, preserving the temperature and reacting for 1.5 hours after dropwise adding, and finishing the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 85 percent.
Example 12
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a 2000ml four-neck bottle, cooling to 0-5 ℃, adding 185g of potassium tert-butoxide in batches, controlling the temperature to 0-5 ℃, ending the feeding, slowly heating to 15-20 ℃, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to 15-20 ℃, preserving the temperature and reacting for 1.5 hours after the dropwise adding is finished, and ending the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 75 percent.
Example 13
Adding 500g of tetrahydrofuran into a four-neck flask, adding 163.3g of 2, 6-diethyl-4-methylaniline and 1.6g of cuprous iodide, cooling to 5-10 ℃, dropwise adding 123g of isoamyl nitrite, controlling the temperature to 5-10 ℃, after dropwise adding, keeping the temperature for reacting for about 2 hours, and keeping the temperature of a diazo solution for later use after the reaction is finished.
And (2) adding 176g of diethyl malonate and 300g N, N-dimethylformamide into a four-mouth bottle, cooling to 0-5 ℃, adding 112g of potassium tert-butoxide in batches, controlling the temperature to 0-5 ℃, slowly heating to 15-20 ℃ after feeding, reacting for 1 hour, dropwise adding the diazonium solution prepared in the step (1) into the reaction solution, controlling the temperature to 15-20 ℃, preserving the temperature and reacting for 1.5 hours after dropwise adding, and finishing the reaction. And adding the reaction solution into 1000g of water, stirring for 0.5 hour, cooling to 0-5 ℃, stirring for 1 hour, and filtering to obtain a crude product. Adding 400g of n-hexane into the crude product, heating to 55-60 ℃, stirring for 1 hour, cooling to 5-10 ℃, stirring for 1 hour, and filtering to obtain a light yellow solid, namely diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate (content: 98%), yield: 80 percent.
TABLE 2 influence of different amounts of potassium tert-butoxide on the yield
| Examples | nPotassium tert-butoxide:nMalonic acid diethyl ester | Yield% |
| 1 | 1.1:1 | 92 |
| 10 | 1:1 | 86 |
| 11 | 1.3:1 | 85 |
| 12 | 1.5:1 | 75 |
| 13 | 0.9:1 | 80 |
Claims (10)
1. A synthetic method of diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate is characterized in that the synthetic route is as follows:
the method comprises the following steps:
step (1), diazotization reaction: under the action of a catalyst, reacting 2, 6-diethyl-4-methylaniline with isoamyl nitrite to obtain 2, 6-diethyl-4-methylphenyl diazonium salt; wherein the catalyst is cuprous chloride or cuprous iodide; the reaction temperature is 5-10 ℃;
reacting the 2, 6-diethyl-4-methylphenyl diazonium salt with diethyl malonate under an alkaline condition to obtain diethyl 2- (2, 6-diethyl-4-methylphenyl) malonate; wherein the reaction temperature is 15-20 ℃.
2. The method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate according to claim 1, wherein in the step (1), the molar ratio of 2, 6-diethyl-4-methylaniline to isoamyl nitrite is 1:1 to 1.5; the reaction solvent is tetrahydrofuran, acetonitrile, N-dimethylformamide, acetone, 1, 2-dichloroethane, dichloromethane and toluene.
3. The method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate according to claim 1, wherein in the step (1), the amount of the catalyst is 0.5 to 3 wt% based on the weight of the 2, 6-diethyl-4-methylaniline.
4. The method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate according to claim 3, wherein in the step (1), the amount of the catalyst is 0.8 to 1.5 wt% based on the weight of the 2, 6-diethyl-4-methylaniline.
5. The method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate according to claim 1, wherein in the step (2), the molar ratio of diethyl malonate to 2, 6-diethyl-4-methylaniline is 1-1.5: 1; the reaction solvent is N, N-dimethylformamide, acetone, acetonitrile and tetrahydrofuran.
6. The method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate according to claim 1, wherein the base is one or more of sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, sodium hydroxide and potassium hydroxide.
7. The method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate according to claim 6, wherein the base is sodium ethoxide, sodium hydride, or potassium tert-butoxide.
8. The method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate according to claim 1, wherein in the step (2), when the base is potassium tert-butoxide, the molar ratio of potassium tert-butoxide to diethyl malonate is 0.9 to 1.3: 1.
9. The method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate according to claim 8, wherein the molar ratio of potassium tert-butoxide to diethyl malonate is 1.1-1.3: 1.
10. The method for synthesizing diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate according to claim 1, comprising the purification of diethyl 2- (2, 6-diethyl-4-methylbenzene) malonate: adding water into the reaction solution obtained in the step (2) to quench the reaction, cooling to 0-5 ℃, filtering to obtain a crude product, and recrystallizing the crude product with n-hexane to obtain a pure 2- (2, 6-diethyl-4-methylbenzene) diethyl malonate product.
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