CN113999138B - Method for rapidly synthesizing citral by using methyl heptenone - Google Patents
Method for rapidly synthesizing citral by using methyl heptenone Download PDFInfo
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- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
Abstract
The invention provides a method for synthesizing lemon nitrile from methyl heptenone. In the method, alkyl sulfide and halogenated acetonitrile react with a cyanomethyl sulfide salt intermediate, and methyl heptenone reacts with cyanomethyl sulfide salt under the action of a base catalyst to obtain a lemon nitrile product. The invention has novel synthetic route, uses simple and easily available methyl heptenone, chloroacetonitrile and alkyl sulfide with relatively low cost as initial raw materials, rapidly reacts to obtain the lemon nitrile product, has short synthetic route and high reaction yield, and has better potential economic value. Secondly, inorganic iodized salt and a phase transfer catalyst are sequentially added in the synthesis reaction, and the iodized salt promotes the rapid generation of the cyanomethyl sulfide; the phase transfer catalyst promotes the dissolution of inorganic alkali, effectively improves the rate and selectivity of the condensation reaction of methyl heptenone and cyanomethyl sulfide salt, and improves the reaction yield. Finally, the invention also realizes one-pot salification and condensation, simplifies the operation of synthesizing the lemon nitrile from the methyl heptenone, and basically keeps the yield.
Description
Technical Field
The invention belongs to the fields of fine chemical engineering and essence and spice, and particularly relates to a method for rapidly synthesizing citral by using methyl heptenone.
Background
The technical name of the citral is 3, 7-dimethyl 2, 6-octadiene-1-nitrile, also called orange flower nitrile and geranonitrile, and the commercial citral is generally a cis-trans mixture, is colorless or pale yellow liquid, and has a boiling point of 220 ℃. The lemon nitrile has fresh lemon fragrance, and can be used for preparing flower fragrance type and fruit fragrance type essence. The selective reduction of the cyano conjugated double bond in the lemon nitrile molecule can produce citronellonitrile, which has fresh lemon fruit and green tea aroma, and is a high-quality spice for modulating citrus aroma.
The general preparation method of the citral is to take citral and hydroxylamine as raw materials, the citral and the hydroxylamine are subjected to condensation reaction to obtain an oxime intermediate, and then the oxime is subjected to dehydration agent to obtain a citral product. Shen Ruiman et al examined the influence of different aldehyde contents, alkali solution and catalyst, dehydration temperature on the yield of citral by using litsea cubeba oil (citral as the main component) as a raw material, and obtained the citral product (fine chemical industry, 1994,11,28) at a yield of 66% at most. The method is characterized in that the farming good et al takes citral as a raw material, reaction conditions are optimized by using an orthogonal experiment, when the mole ratio of citral to hydroxylamine hydrochloride to sodium carbonate is 1:1.5:1.2, the citral and the hydroxylamine react at the temperature of 70 ℃ to generate citral oxime, then the citral oxime is dehydrated by acetic anhydride at the temperature of 100 ℃ to 105 ℃, and the yield of the citral can reach 85% (Guangxi chemical industry, 1997,26,8). Cui Zhimin et al used citral and hydroxylamine sulfate as raw materials and determined that the optimal reaction conditions for oximation by orthogonal experiments were as follows: the molar ratio of citral to hydroxylamine sulfate is 1:1.5, the reaction temperature is 45 ℃, the reaction time is 3.5 hours, and the pH value of the solution is controlled between 6 and 7; lemon oxime was obtained in 91.5% yield under this condition; the lemon oxime was dehydrated with 5 equivalents of acetic anhydride. Lemon nitrile (chemical world, 2003,4,206-208) was obtained in 89.7% yield. Zhou Wenfu et al also used litsea cubeba oil as a raw material and reacted directly with hydroxylamine sulfate to give a lemoxime, which was then dehydrated under acetic anhydride and phase transfer catalyst to give a citral yield of 70% in the best reaction conditions (fine chemical, 2005,22,515).
Among known methods for synthesizing citral from citral, there are also methods in which expensive hydroxylamine and a dehydrating agent are not used, and for example, zheng Hailin et al report a method for synthesizing citral by gas phase ammonification, which uses citral as a raw material, gasifies it, and ammonifies it at 250 ℃ under the action of a copper molecular sieve catalyst to obtain citral with a yield of 90% or more (university of Guangxi, 1996,21,283). Later Li Jilie reports a liquid phase direct ammonification method, which uses citral as a raw material, and makes the citral and ammonia water undergo an ammonification reaction under the action of a catalyst, and then adds an oxidant such as hydrogen peroxide, so as to obtain a citral product (CN 102675147A) with a yield of 90% at most.
In summary, the existing method for synthesizing the lemon nitrile mainly takes the relatively expensive citral and hydroxylamine as raw materials, and performs 2-step reactions such as oximation, dehydration and the like to obtain the lemon nitrile product, so that the raw materials are expensive, the reaction route is long, and the operation is inconvenient; in the dehydration step, excessive dehydrating agent is generally needed, a large amount of byproducts such as acetic acid are produced as byproducts, and the atomic economy is poor. Therefore, a method for synthesizing the lemon nitrile simply and efficiently from low-cost raw materials, and generating no or little three wastes in the synthesis process is needed to be developed at present, so that the production cost of the lemon nitrile is reduced.
Disclosure of Invention
In view of the above problems in the preparation of citral, an object of the present invention is to provide a method for synthesizing citral which can synthesize citral from methyl heptenone (6-methyl-5-hepten-2-one) efficiently and rapidly.
In order to achieve the above-mentioned invention effect, the invention adopts the following technical scheme:
a process for the rapid synthesis of citral from methyl heptenone, comprising the following reaction steps:
s1: under the promotion of iodized salt, alkyl sulfide reacts with substituted acetonitrile to obtain a cyanomethyl sulfide salt intermediate;
s2: and under the action of a base catalyst and a phase transfer catalyst, performing a condensation reaction on the cyanmethystate intermediate and methyl heptenone to obtain the lemon nitrile.
The reaction scheme is as follows:
in the reaction route, alkyl sulfide and substituted acetonitrile are reacted completely for 2-4 hours, the obtained cyanomethyl sulfide is directly separated out from a reaction system and then reacts with methylheptyl, the reaction is complete within 2-4 hours, and the highest yield is 96 percent, so that the lemon nitrile is obtained; furthermore, the method can also carry out two-step reaction by a one-pot method, and has simpler operation and only slightly reduced yield. Overall, the method has the advantages of simple operation and high reaction yield, and can efficiently and rapidly obtain the lemon nitrile product.
In the invention, the alkyl sulfide in S1 is one or more of dimethyl sulfide, methyl ethyl sulfide, diethyl sulfide, dipropyl sulfide, methyl propyl sulfide, ethyl propyl sulfide and dibutyl sulfide, preferably dimethyl sulfide and/or diethyl sulfide; preferably, the alkyl sulfide is used in an amount of 100 to 130mol% based on the molar amount of the substituted acetonitrile.
In the invention, the substituted acetonitrile in S1 is one or more of fluoroacetonitrile, chloroacetonitrile, bromoacetonitrile, iodoacetonitrile, cyanomethyl benzene sulfonate and cyanomethyl p-methylbenzene sulfonate, and preferably chloroacetonitrile.
In the invention, the iodized salt in S1 is one or more of lithium iodide, sodium iodide, potassium iodide, zinc iodide and iron iodide; preferably, the iodized salt is used in an amount of 0.1 to 3.0mol% based on the molar amount of the substituted acetonitrile.
In the invention, the reaction temperature of the reaction of S1 is 60-90 ℃, preferably 60-80 ℃; the reaction pressure is normal pressure; the reaction time is 2-4 hours.
In the invention, the alkali catalyst in S2 is one or more of sodium hydroxide, potassium hydroxide, cesium hydroxide, potassium carbonate, sodium carbonate, potassium phosphate, sodium methoxide, sodium ethoxide, sodium tert-butoxide and potassium tert-butoxide, preferably potassium carbonate and/or sodium carbonate; preferably, the base catalyst is used in an amount of 105 to 150mol% based on the molar amount of methyl heptenone.
In the invention, the feeding mole ratio of the cyanmethysulfide intermediate and the methyl heptenone (1.0-1.2) of S2 is 1.0;
in the invention, the phase transfer catalyst S2 is one or more of tetrapropylammonium chloride, tetrabutylammonium chloride, benzyl triethylammonium chloride, trioctylmethyl ammonium chloride, dodecyl triethylammonium bromide, tetrabutylphosphine bromide and polydiethanol-400; preferably, the phase transfer catalyst is used in an amount of 0.1 to 3.0mol% based on the molar amount of methyl heptenone.
In the invention, the condensation reaction of S2 is carried out in one or more solvents of diethyl ether, methyl tertiary butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1, 4-dioxane, N-dimethylformamide, N-dimethylethylamide, dimethyl sulfoxide and N-methylpyrrolidone, preferably one or more solvents of tetrahydrofuran, 2-methyltetrahydrofuran and N, N-dimethylformamide; preferably, the solvent is used in an amount such that the molar concentration of methyl heptenone is between 0.5 and 5mol/L.
In the invention, the condensation reaction temperature of S2 is 50-90 ℃, preferably 60-80 ℃; the reaction pressure is normal pressure; the reaction time is 2-6 hours.
In the invention, after the condensation reaction of S2 is completed, inorganic salt is removed by filtration, solvent is removed by distillation, and a crude product of the lemon nitrile is obtained, and the obtained crude product is washed by water and then is subjected to vacuum rectification, so that a pure lemon nitrile product is obtained.
It is another object of the present invention to provide a citral.
The citrate is prepared by adopting the synthesis method, and the citrate is prepared by synthesizing methyl heptenone as raw material.
Compared with the prior art, the invention has the following positive effects:
1. the synthetic route is novel, and the method takes the methyl heptenone, chloroacetonitrile and dimethyl sulfide which are simple and easy to obtain and low in price as the initial raw materials, so that the method has the advantage of cost;
2. the synthesis process is simple, the quick reaction is carried out to obtain the lemon nitrile product, the yield is high (up to 96 percent), the operation is simple and convenient, and the method is suitable for large-scale production; only inorganic salt is by-produced in the whole reaction process, waste water and waste liquid are not generated, and the inorganic salt has high purity and can be sold out.
3. The addition of catalytic amount of iodized salt and phase transfer catalyst can effectively accelerate the reaction of thioether and substituted acetonitrile and shorten the generation time of cyano sulfur salt; the phase transfer catalyst can accelerate the condensation reaction between cyano sulfur salt and methyl heptenone, and improve the reaction selectivity and yield.
4. The salification and condensation reaction can be carried out by adopting a one-pot method, the operation can be further simplified, and the product yield is basically maintained compared with the single salification and condensation reaction.
Detailed Description
The present invention will be described in detail with reference to examples, but the present invention is not limited to the examples.
The main raw material information is as follows:
dimethyl sulfide, diethyl sulfide, methyl ethyl sulfide, dipropyl sulfide, chloroacetonitrile, purity 98-99%, shanghai Michael chemistry. Cyanomethyl benzene sulfonate, 98%, shanghai vast technology.
Bromoacetonitrile, potassium iodide, sodium iodide, zinc iodide, an Naiji chemistry, 99%; polyethylene glycol 400, ar, an Naiji.
Potassium carbonate, sodium hydroxide, potassium hydroxide, sodium carbonate, AR, aara Ding Shiji; tetrabutylammonium chloride, benzyltriethylammonium chloride, 98%, and alar Ding Shiji.
Tetrahydrofuran, ethyl acetate, toluene, methyl tert-butyl ether, a national agent, AR. The purity of the oxepin is higher than 99.5 percent.
Citral, 99%, self-produced; hydroxylamine sulfate, sodium carbonate, acetic anhydride, alar Ding Shiji, 99%.
The gas chromatography test conditions of the present invention are as follows:
instrument model: agilent 7890B; gas chromatographic column: HP-5 19091J-413 capillary column; solvent: dichloromethane; sample injection volume: 1 μl; sample inlet temperature: 240 ℃; split ratio: 35/1; hydrogen flow rate: 40mL/min; tail blow flow: 25mL/min; air flow rate: 400mL/min; column flow rate: 1.5mL/min; heating program: the initial column temperature is 35 ℃, and the column is kept for 5min; raising the temperature to 100 ℃ at a speed of 6 ℃/min; then the temperature is raised to 240 ℃ at a speed of 30 ℃/min, and the mixture is kept for 5min.
Example 1
Synthesizing the citral by using methyl heptenone, dimethyl sulfide and chloroacetonitrile.
Anhydrous tetrahydrofuran (500 mL), dimethyl sulfide (102.5 g,1.65 mmol) and potassium iodide (2.49 g,0.015 mol) were sequentially added to a 1000mL three-necked flask equipped with a magnetic stirrer at room temperature under a nitrogen atmosphere, a reflux condenser was connected to the top of the three-necked flask, the three-necked flask was placed in an oil bath at 80 ℃, stirring was started, chloroacetonitrile (113.3 g,1.50 mol) was added dropwise to the reaction solution, and after 1.0h, the addition was completed. As the reaction proceeds, the intermediate cyanomethyl sulfide gradually precipitates, and the reaction solution becomes turbid from clear. After 2.0h of reaction with rapid stirring, the flask was removed from the oil bath, cooled to room temperature, filtered and dried to give 192.0g of the cyanomethyl sulfide salt intermediate in 93% yield (calculated as chloroacetonitrile).
The cyanomethyl sulfide salt intermediate (192.0 g,1.40 mol) obtained in the previous step, solvent anhydrous tetrahydrofuran (600 mL), methyl heptenone (167.8 g,1.33 mol) and tetrabutylammonium chloride (3.68 g,0.0133 mol) serving as a phase transfer catalyst are sequentially added into a three-port bottle, and a reflux condenser is connected above the three-port bottle; stirring was started, and finally potassium carbonate powder (192.3 g,1.39 mol) was added to the reaction solution, the temperature of the reaction solution was raised to 80℃and the reaction was carried out with rapid stirring for 3.0h. After the GC detects complete disappearance of the starting methylheptenone, the reaction is stopped. After working up, the reaction mixture was cooled to room temperature, inorganic salts (potassium chloride and potassium bicarbonate as main components) were removed by filtration, tetrahydrofuran (4 kPa,30 ℃) was removed by rotary evaporation to give a crude product of lemon nitrile, the obtained crude product was washed with deionized water and saturated brine in this order, and then distilled under reduced pressure (0.26 kPa,81-84 ℃) to give 183.9g of the lemon nitrile product in 93% yield (calculated as methyl heptenone). Product of lemon nitrile high resolution mass spectrum HRMS-EI M + calcd for C 5 H 12 O 2 :149.1204,found 149.1202。
Example 2
Synthesizing the citral by using methyl heptenone, dimethyl sulfide and chloroacetonitrile.
Anhydrous tetrahydrofuran (500 mL), dimethyl sulfide (121.2 g,1.95 mmol) and potassium iodide (1.25 g,0.005 mol) were sequentially added to a 1000mL three-necked flask equipped with a magnetic stirrer at room temperature under a nitrogen atmosphere, a reflux condenser was connected to the top of the three-necked flask, the three-necked flask was placed in an oil bath at 60℃and stirring was turned on, chloroacetonitrile (113.3 g,1.50 mol) was added dropwise to the reaction solution, and after 0.5h, the addition was completed. As the reaction proceeds, the intermediate cyanomethyl sulfide gradually precipitates, and the reaction solution becomes turbid from clear. After 3.5h of reaction with rapid stirring, the flask was removed from the oil bath, cooled to room temperature, filtered and dried to give 194.1g of a cyanomethyl sulfide salt intermediate in 94% yield (calculated as chloroacetonitrile).
The cyanomethyl sulfide intermediate (194.1 g,1.41 mol) obtained in the previous step, solvent anhydrous tetrahydrofuran (600 mL), methyl heptenone (177.9 g,1.41 mol) and tetrabutylammonium chloride (3.92 g,0.0141 mol) as phase transfer catalyst are sequentially added into a three-necked flask, and a reflux condenser is connected above the three-necked flask; stirring was started, and finally potassium carbonate powder (233.8 g,1.69 mol) was added to the reaction mixture, the temperature of the reaction mixture was raised to 90℃and the reaction was carried out for 2.0h with rapid stirring. After the GC detects complete disappearance of the starting methylheptenone, the reaction is stopped. After working up, the reaction mixture was cooled to room temperature, inorganic salts (potassium chloride and potassium bicarbonate as main components) were removed by filtration, tetrahydrofuran (4 kPa,30 ℃) was removed by rotary evaporation to give a crude product of lemon nitrile, the obtained crude product was washed with deionized water and saturated brine in this order, and then distilled under reduced pressure (0.26 kPa,81-84 ℃) to give 191.5g of the lemon nitrile product in 91% yield (calculated as methyl heptenone).
Example 3
Synthesizing the citral by using methyl heptenone, dimethyl sulfide and chloroacetonitrile.
Anhydrous tetrahydrofuran (500 mL), dimethyl sulfide (93.2 g,1.5 mmol) and potassium iodide (7.47 g,0.045 mol) were sequentially added to a 1000mL three-necked flask equipped with a magnetic stirrer at room temperature under a nitrogen atmosphere, a reflux condenser was connected to the top of the three-necked flask, the three-necked flask was placed in an oil bath at 80 ℃, stirring was started, chloroacetonitrile (113.3 g,1.50 mol) was added dropwise to the reaction solution, and after 1.0h, the addition was completed. As the reaction proceeds, the intermediate cyanomethyl sulfide gradually precipitates, and the reaction solution becomes turbid from clear. After 1.0h of reaction under rapid stirring, the flask was removed from the oil bath, cooled to room temperature, filtered and dried to give 181.7g of a cyanomethyl sulfide salt intermediate in 88% yield (calculated as chloroacetonitrile).
The cyanomethyl sulfide salt intermediate (181.7 g,1.32 mol), solvent anhydrous tetrahydrofuran (500 mL), methyl heptenone (138.8 g,1.10 mol) and tetrabutylammonium chloride (1.53 g,0.0055 mol) which are phase transfer catalysts obtained in the previous step are sequentially added into a three-mouth bottle, and a reflux condenser is connected above the three-mouth bottle; stirring was started, and finally potassium carbonate powder (167.3 g,1.21 mol) was added to the reaction solution, the temperature of the reaction solution was raised to 50℃and the reaction was carried out for 6.0h with rapid stirring. After the GC detects complete disappearance of the starting methylheptenone, the reaction is stopped. After working up, the reaction mixture was cooled to room temperature, inorganic salts (potassium chloride and potassium bicarbonate as main components) were removed by filtration, tetrahydrofuran (4 kPa,30 ℃) was removed by rotary evaporation to give a crude product of lemon nitrile, the obtained crude product was washed with deionized water and saturated brine in this order, and then subjected to rectification under reduced pressure (0.26 kPa,81-84 ℃) to give 142.8g of the lemon nitrile product in a yield of 87% (calculated as methyl heptenone).
Example 4
Synthesizing the citral by using methyl heptenone, methyl ethyl sulfide and chloroacetonitrile.
Ethyl acetate (450 mL), methyl ethyl sulfide (104.0 g,1.37 mmol) and sodium iodide (0.19 g,0.0013 mol) were sequentially added to a 1000mL three-necked flask equipped with a magnetic stirrer at room temperature under a nitrogen atmosphere, a reflux condenser was connected to the top of the three-necked flask, the three-necked flask was placed in an oil bath at 80℃and stirring was turned on, chloroacetonitrile (98.15 g,1.30 mol) was added dropwise to the reaction solution, and the addition was completed after 1.0 h. As the reaction proceeds, the intermediate cyanomethyl sulfide gradually precipitates, and the reaction solution becomes turbid from clear. After 3h of reaction with rapid stirring, the flask was removed from the oil bath, cooled to room temperature, filtered and dried to give 177.44g of the cyanomethylsulfonate intermediate in 90% yield (calculated as chloroacetonitrile).
The cyanomethyl sulfide intermediate (161.0 g,1.17 mol) obtained in the previous step, solvent anhydrous tetrahydrofuran (550 mL), methyl heptenone (134.36 g,1..07 mol) and tetrabutylammonium chloride (8.88 g,0.0319 mol) as phase transfer catalysts were added into a three-necked flask in sequence, and a reflux condenser tube was connected above the three-necked flask; stirring was started, and finally potassium carbonate powder (178.28 g,1.29 mol) was added to the reaction solution, the temperature of the reaction solution was raised to 80℃and the reaction was carried out with rapid stirring for 3.0h. After the GC detects complete disappearance of the starting methylheptenone, the reaction is stopped. After working up, the reaction mixture was cooled to room temperature, inorganic salts were removed by filtration, tetrahydrofuran (4 kPa,30 ℃ C.) was removed by rotary evaporation to give a crude product of citral, and the obtained crude product was washed with deionized water and saturated brine in this order, and then distilled under reduced pressure (0.26 kPa,81-84 ℃ C.) to give 172.33g of citral product in 94% yield (calculated as methylheptenone).
Example 5
Synthesizing the citral by using methyl heptenone, diethyl sulfide and chloroacetonitrile.
Ethyl acetate (500 mL), diethyl sulfide (148.8 g,1.65 mmol) and sodium iodide (4.50 g,0.03 mol) were sequentially added to a 1000mL three-necked flask equipped with a magnetic stirrer at room temperature under a nitrogen atmosphere, a reflux condenser was connected to the top of the three-necked flask, the three-necked flask was placed in an oil bath at 85℃and stirring was turned on, chloroacetonitrile (113.3 g,1.50 mol) was added dropwise to the reaction solution, and the addition was completed after 1.0 h. As the reaction proceeds, the intermediate cyanomethyl sulfide gradually precipitates, and the reaction solution becomes turbid from clear. After 3h of reaction with rapid stirring, the flask was removed from the oil bath, cooled to room temperature, filtered and dried to give 238.58g of the cyanomethylsulfonate intermediate in 96% yield (calculated as chloroacetonitrile).
The cyanomethyl sulfide intermediate (198.2 g,1.44 mol) obtained in the previous step, solvent anhydrous tetrahydrofuran (600 mL), methyl heptenone (181.72 g,1.44 mol) and phase transfer catalyst benzyl triethyl ammonium chloride (6.56 g,0.0288 mol) are sequentially added into a three-port bottle, and a reflux condenser is connected above the three-port bottle; stirring was started, and finally potassium carbonate powder (192.3 g,1.39 mol) was added to the reaction solution, the temperature of the reaction solution was raised to 80℃and the reaction was carried out with rapid stirring for 3.0h. After the GC detects complete disappearance of the starting methylheptenone, the reaction is stopped. After working up, the reaction mixture was cooled to room temperature, inorganic salts were removed by filtration, tetrahydrofuran (4 kPa,30 ℃ C.) was removed by rotary evaporation to give a crude product of citral, and the obtained crude product was washed with deionized water and saturated brine in this order, and then distilled under reduced pressure (0.26 kPa,81-84 ℃ C.) to give 206.3g of citral product in 96% yield (calculated as methylheptenone).
Example 6
Synthesizing the lemon nitrile from methyl heptenone, dipropyl thioether and cyanomethyl benzene sulfonate.
Anhydrous toluene (700 mL), dipropyl sulfide (136.6 g,1.16 mmol) and zinc iodide (1.76 g,0.0055 mol) are sequentially added into a 1000mL three-necked flask equipped with a magnetic stirrer at room temperature under a nitrogen atmosphere, a reflux condenser is connected above the three-necked flask, the three-necked flask is placed into an oil bath at 90 ℃, stirring is started, and cyanotoluene sulfonate (216.93 g,1.10 mol) is dropwise added into the reaction solution after 1.5 h. As the reaction proceeds, the intermediate cyanomethyl sulfide gradually precipitates, and the reaction solution becomes turbid from clear. After 2h of reaction with rapid stirring, the flask was removed from the oil bath, cooled to room temperature, filtered and dried to give 319.24g of a cyanomethylsulfonate intermediate in 92% yield (calculated as cyanomethyl benzenesulfonate).
The cyanmethyl sulfide intermediate (319.24 g,1.01 mol) obtained in the previous step, solvent anhydrous tetrahydrofuran (600 mL), methyl heptenone (127.71 g,1.01 mol) and tetrabutylammonium chloride (0.281g, 0.001 mol) serving as a phase transfer catalyst are sequentially added into a three-port bottle, and a reflux condenser is connected above the three-port bottle; stirring was started, and finally potassium hydroxide powder (146.86 g,1..06 mol) was added to the reaction mixture, the temperature of the reaction mixture was raised to 80 ℃, and the reaction was carried out for 5.0h with rapid stirring. After the GC detects complete disappearance of the starting methylheptenone, the reaction is stopped. After working up, the reaction mixture was cooled to room temperature, inorganic salts were removed by filtration, and the solvent tetrahydrofuran (4 kPa,30 ℃ C.) was removed by rotary evaporation to give a crude product of citral, and the obtained crude product was washed successively with deionized water and saturated brine, and then subjected to rectification under reduced pressure (0.26 kPa,81-84 ℃ C.) to give 137.43g of the citral product in a yield of 91% in terms of methylheptenone.
Example 7
Synthesizing the citral by using methyl heptenone, dimethyl sulfide and bromoacetonitrile.
Anhydrous ethyl acetate (300 mL), dimethyl sulfide (55.45 g,0.89 mmol) and sodium iodide (1.27 g,0.0085 mol) are sequentially added into a 1000mL three-necked flask equipped with a magnetic stirrer at room temperature under a nitrogen atmosphere, a reflux condenser is connected above the three-necked flask, the three-necked flask is placed into an oil bath at 70 ℃, stirring is started, bromoacetonitrile (102.0 g,0.85 mol) is dropwise added into the reaction solution, and the addition is completed after 0.5 h. As the reaction proceeds, the intermediate cyanomethyl sulfide gradually precipitates, and the reaction solution becomes turbid from clear. After 3h of reaction with rapid stirring, the flask was removed from the oil bath, cooled to room temperature, filtered and dried to give 150.13g of the cyanomethylsulfonate intermediate in 97% yield (calculated as bromoacetonitrile).
The cyanomethyl sulfide intermediate (150.13 g, 0.823mol) obtained in the previous step, solvent anhydrous methyl tertiary butyl ether (400 mL), methyl heptenone (98.9 g,0.783 mol) and phase transfer catalyst polyethylene glycol 400 (2.18 g) are sequentially added into a three-necked flask, and a reflux condenser is connected above the three-necked flask; stirring was started, and finally small sodium hydroxide particles (47.0 g,1.18 mol) were added to the reaction solution, the temperature of the reaction solution was raised to 80℃and the reaction was carried out for 2.0h with rapid stirring. After the GC detects complete disappearance of the starting methylheptenone, the reaction is stopped. After working up, the reaction mixture was cooled to room temperature, inorganic salts were removed by filtration, and the solvent anhydrous methyl t-butyl ether (4 kPa,30 ℃ C.) was removed by rotary evaporation to give a crude product of citral, and the obtained crude product was washed successively with deionized water and saturated brine, and then subjected to rectification under reduced pressure (0.26 kPa,81-84 ℃ C.) to give 112.21g of the citral product in 96% yield (calculated as methyl heptenone).
Example 8
Synthesizing the citral by using methyl heptenone, dimethyl sulfide and bromoacetonitrile.
Anhydrous tetrahydrofuran (500 mL), dimethyl sulfide (91.34 g,1.47 mmol) and zinc iodide (0.45 g,0.0014 mol) were sequentially added to a 1000mL three-necked flask equipped with a magnetic stirrer at room temperature under a nitrogen atmosphere, a reflux condenser was connected to the top of the three-necked flask, the three-necked flask was placed in an oil bath at 80℃and stirring was turned on, bromoacetonitrile (209.9 g,1.40 mol) was added dropwise to the reaction solution, and the addition was completed after 1.5 hours. As the reaction proceeds, the intermediate cyanomethyl sulfide gradually precipitates, and the reaction solution becomes turbid from clear. After 1.5h of reaction with rapid stirring, the flask was removed from the oil bath, cooled to room temperature, filtered and dried to give 237.1g of the cyanomethylsulfonate intermediate in 93% yield (calculated as bromoacetonitrile).
The cyanomethyl sulfide salt intermediate (237.1 g,1.30 mol), solvent anhydrous tetrahydrofuran (600 mL), methyl heptenone (161.0 g,1.28 mol) and phase transfer catalyst polyethylene glycol (3.55 g) obtained in the previous step are sequentially added into a three-mouth bottle, and a reflux condenser is connected above the three-mouth bottle; stirring was started, and finally potassium hydroxide powder (78.8 g,1.40 mol) was added to the reaction mixture, the temperature of the reaction mixture was raised to 80℃and the reaction was carried out for 2.0h with rapid stirring. After the GC detects complete disappearance of the starting methylheptenone, the reaction is stopped. After working up, the reaction mixture was cooled to room temperature, inorganic salts were removed by filtration, tetrahydrofuran (4 kPa,30 ℃ C.) was removed by rotary evaporation to give a crude product of citral, and the obtained crude product was washed successively with deionized water and saturated brine, and then distilled under reduced pressure (0.26 kPa,81-84 ℃ C.) to give 175.2g of a product of citral in 92% yield (calculated as methylheptenone).
Example 9
The method synthesizes the citral by a one-pot method of methyl heptenone, dimethyl sulfide and chloroacetonitrile.
Anhydrous tetrahydrofuran (500 mL), dimethyl sulfide (97.9 g,1.58 mmol) and sodium iodide (0.45 g, 0.003mol) were sequentially added to a three-necked flask equipped with a magnetic stirrer at room temperature under a nitrogen atmosphere, a reflux condenser was connected to the top of the three-necked flask, the three-necked flask was placed in an oil bath at 80℃and stirring was turned on, chloroacetonitrile (113.3 g,1.50 mol) was added dropwise to the reaction solution, and after 1.0h, the addition was completed. As the reaction proceeds, the intermediate cyanomethyl sulfide gradually precipitates, and the reaction solution becomes turbid from clear. After reacting for 2 hours under rapid stirring, methyl heptenone (172.6 g,1.37 mol) and tetrabutylammonium chloride (3.80 g,0.0137 mol) serving as phase transfer catalysts are added into a reaction bottle in sequence, and a reflux condenser is connected above the three bottles; stirring is started, and finally sodium hydroxide (65.64 g,1.64 mol) is slowly added into the reaction liquid, so that the reaction liquid is prevented from bumping during the feeding process. The reaction was continued for 2.0h with rapid stirring while maintaining the temperature of the reaction at 80 ℃. After the GC detects complete disappearance of the starting methylheptenone, the reaction is stopped. After working up, the reaction mixture was cooled to room temperature, the inorganic salts were removed by filtration, the solvent tetrahydrofuran was removed by rotary evaporation (4 kPa,30 ℃ C.) to give a crude product of citral, the crude product was washed successively with deionized water and saturated brine, and then distilled under reduced pressure (0.26 kPa,81-84 ℃ C.) to give 183.7g of citral product in a yield of 90% (calculated as raw material methyl heptenone).
Comparative example 1
The prior art is used to synthesize citral from citral, hydroxylamine sulfate and acetic anhydride (chemical world, 2003,4,206-208).
To a 2L three-necked flask equipped with a magnetic stirrer, 1.8mol of hydroxylamine sulfate (295.45 g) and 900mL of water were sequentially added at room temperature under nitrogen atmosphere, a certain amount of sodium carbonate (1.71 mol,181.24 g) was added to control the pH of the solution to be=6.5, 1.2mol of citral (182.68 g) was added dropwise over 2 hours, and the reaction temperature was controlled at 45℃for 3 hours. After the GC detects complete disappearance of the raw material citral, the reaction is stopped. And (3) after-treatment, transferring the reaction solution into a separating funnel, standing for layering, separating a water layer, and enabling an oil layer to be orange red. The oil phase was washed sequentially with saturated aqueous NaCl solution 2 times and then with distilled water 2 times. After drying over anhydrous sodium sulfate, distillation was carried out under reduced pressure at 0.13kPa, and a fraction at 103℃was collected, 180.6g of a reaction intermediate, namely, citral oxime was obtained, with a yield of 90% (based on citral). A certain amount of acetic anhydride (4.5 mol,551.28 g) serving as a dehydrating agent is added into a 2L three-neck round bottom flask, after the mixture is heated to 80 ℃, the obtained lemon oxime (1.08 mol) is dripped for 60 minutes, the reaction temperature is controlled to float between 125 and 130 ℃ in the dripping process, and the stirring reaction time is continued for 1 hour after the dripping is finished. After the reaction was completed, naturally cooled to room temperature, the reaction solution was transferred to a separating funnel, the oil layer was washed with 50mL of distilled water, saturated aqueous sodium bicarbonate solution, and saturated brine in this order, acetic anhydride which did not react completely was removed, and the washed aqueous phase was discarded, and the oil layer was collected. Drying the oil layer by anhydrous sodium sulfate, distilling under reduced pressure at 0.27kPa, and collecting fraction at 85 ℃ to obtain 141.8g of product lemon nitrile with a yield of 88%; the total yield of the two reactions was 79% (calculated from the raw material citral).
Claims (10)
1. A process for the rapid synthesis of citral from methylheptenone, characterized in that it comprises the following reaction steps:
s1: under the promotion of iodized salt, alkyl sulfide reacts with substituted acetonitrile to obtain a cyanomethyl sulfide salt intermediate;
s2: under the action of a base catalyst and a phase transfer catalyst, performing a condensation reaction on a cyanomethyl sulfide intermediate and methyl heptenone to obtain the lemon nitrile;
wherein the substituted acetonitrile in S1 is one or more of fluoroacetonitrile, chloroacetonitrile, bromoacetonitrile, iodoacetonitrile, cyanomethyl benzenesulfonate and cyanomethyl p-toluenesulfonate.
2. The synthetic method according to claim 1, wherein S1 is one or more of dimethyl sulfide, methyl ethyl sulfide, diethyl sulfide, dipropyl sulfide, methyl propyl sulfide, ethyl propyl sulfide and dibutyl sulfide;
and/or, S1 the substituted acetonitrile is chloroacetonitrile;
and/or the iodized salt in the S1 is one or more of lithium iodide, sodium iodide, potassium iodide, zinc iodide and iron iodide.
3. The synthetic method according to claim 2, wherein S1 said alkyl sulfide is dimethyl sulfide and/or diethyl sulfide;
the dosage of the alkyl sulfide is 100-130 mol% of the molar quantity of the substituted acetonitrile;
the dosage of the iodized salt is 0.1-3.0 mol% of the molar quantity of the substituted acetonitrile.
4. The synthetic method according to claim 1 or 2, wherein the reaction temperature of the reaction of S1 is 60 to 90 ℃; the reaction pressure is normal pressure; the reaction time is 2-4 hours.
5. The method according to claim 4, wherein the reaction temperature of the reaction of S1 is 60 to 80 ℃.
6. The synthetic method of claim 1 wherein S2 the base catalyst is one or more of sodium hydroxide, potassium hydroxide, cesium hydroxide, potassium carbonate, sodium carbonate, potassium phosphate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide;
and/or S2, wherein the feeding mole ratio of the cyanmethysulfate intermediate to the methyl heptenone is (1.0-1.2) 1.0;
and/or the phase transfer catalyst in S2 is one or more of tetrapropylammonium chloride, tetrabutylammonium chloride, benzyltriethylammonium chloride, trioctylmethylammonium chloride, dodecyltriethylammonium bromide, tetrabutylphosphine bromide and polydiethanol-400.
7. The method according to claim 6, wherein the base catalyst of S2 is potassium carbonate and/or sodium carbonate;
the dosage of the alkali catalyst is 105-150 mol% of methyl heptenone;
the dosage of the phase transfer catalyst is 0.1 to 3.0mol percent of the molar quantity of the methyl heptenone.
8. The synthetic method according to claim 1, wherein the condensation reaction of S2 is performed in one or more of solvents diethyl ether, methyl tertiary butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1, 4-dioxane, N-dimethylformamide, N-dimethylformamide, dimethyl sulfoxide and N-methylpyrrolidone;
and/or the condensation reaction temperature of S2 is 50-90 ℃; the reaction pressure is normal pressure; the reaction time is 2-6 hours.
9. The synthetic method of claim 8, wherein the condensation reaction of S2 is performed in one or more of the solvents tetrahydrofuran, 2-methyltetrahydrofuran, and N, N-dimethylformamide;
the dosage of the solvent ensures that the molar concentration of the methyl heptenone is 0.5-5 mol/L;
and/or the condensation reaction temperature of S2 is 60-80 ℃.
10. The method according to claim 1, wherein after the condensation reaction of S2 is completed, inorganic salts are removed by filtration, and the solvent is removed by distillation to obtain a crude product of the lemon nitrile, and the obtained crude product is washed with water and then rectified under reduced pressure to obtain a pure lemon nitrile product.
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| CN102675147A (en) * | 2012-05-30 | 2012-09-19 | 中南林业科技大学 | Method for preparing lemonile by using citral and device of preparation method |
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| EP2628723B1 (en) * | 2012-02-15 | 2014-09-10 | DSM IP Assets B.V. | Novel process for the manufacture of methyl limonitrile |
| WO2016028897A1 (en) * | 2014-08-20 | 2016-02-25 | Bedoukian Research, Inc. | Perfume compositons containing isomeric alkadienenitriles |
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| CN1502603A (en) * | 2002-10-15 | 2004-06-09 | ˹��ϣķ | 5,7,7-trimethyloctanenitrile |
| CN101765584A (en) * | 2007-07-26 | 2010-06-30 | 巴斯夫欧洲公司 | Process for the preparation of ethylgeranonitrile |
| CN102015631A (en) * | 2007-10-29 | 2011-04-13 | 玛奈·菲尔萨公司 | Substituted octane(ene) nitriles, methods for the synthesis thereof and uses thereof in perfumery |
| CN102675147A (en) * | 2012-05-30 | 2012-09-19 | 中南林业科技大学 | Method for preparing lemonile by using citral and device of preparation method |
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