CN103058984B - Synthesis method of watermelon ketone - Google Patents

Abstract

The invention discloses a synthesis method of watermelon ketone. Under the protection of nitrogen, sodium carbonate solution and 4-methylcatechol are added to a reactor, the temperature is controlled at 60-80°C for 1-2 hours, and toluene is added in the normal Press down to bring out the water completely, add organic base and ammonium iodide, then add dropwise the mixed solution of 1,3-dichloroacetone and alcohol or butanone at 60-80°C, keep it warm for 3-5 hours after the drop is completed; cool , to get the crude product by suction filtration, and recover toluene; then wash with sodium sulfate solution until neutral, distill under reduced pressure, and recrystallize the fraction with a mixed solvent of acetone and n-hexane to obtain watermelon ketone as a white crystalline solid. The method adopted in the invention synthesizes the target product, the reaction conditions are easy to control, the operation is simple, the yield is high, the production cost is low, the reaction is safe and environment-friendly.

Description

The synthetic method of watermelon ketone

technical field

The invention relates to the technical field of chemical industry, in particular to a method for synthesizing watermelon ketone.

Background technique

Watermelon ketone is called Calone/Watermelon ketone abroad, and its chemical name is 7-methyl-3,4-dihydro-2H-1,5-benzodioxepin-3-one.

With the development of the fragrance industry, watermelon ketone is widely used. Due to the characteristics of watermelon ketone itself, it is a new concept for the preparation of perfume, so it has become a new choice for domestic and foreign fragrance experts. China's demand for watermelon ketone mainly depends on imports. The synthetic method about watermelon ketone mainly contains following several. For example:

U.S. reports use 4-methylcatechol and methyl bromoacetate to condense into the intermediate of dicarboxylates, then under the effect of strong base, by Dieckmann condensation, obtain the compound of 2-methoxyformyl, then Then hydrolyze and decarboxylate in ethanol hydrochloric acid to obtain watermelon ketone.

Canadian chemists used 4-methylcatechol and chloroacetonitrile as starting materials to prepare watermelon ketones. the

Italian chemists condensed 4-methylcatechol and 1,3-dichloropropanol into intermediate benzocycloheptanol, and then oxidized it to obtain watermelon ketone, but the yield was 4%.

In addition, 4-methylcatechol and dichloroacetone are used as raw materials, 4-methylcatechol is condensed, and watermelon ketone can also be obtained through ring formation and rearrangement. Although the reaction steps are simple, watermelon ketone can be synthesized in one step , but the yield can only reach 50%.

In summary, the methods disclosed in the U.S. and Canada all require the use of a strong base NaH as a reagent, the reaction conditions are harsh, the reaction yield is low, and it is not suitable for industrial production; the method disclosed in Italy has too low yield and no use value; Catechol and dichloroacetone are used as raw materials to obtain watermelon ketone through ring formation and rearrangement. Although this method can be used in production, the yield is not very high (only up to 50%).

The applicant's previous patent application, application number 200810244583.7, discloses a synthesis method of watermelon ketone, which is carried out by a one-pot method. The biggest defect is that the yield is also very low (less than 50%).

Contents of the invention

The technical problem to be solved by the present invention is to provide a synthetic method of watermelon ketone, which has the advantages of easy control of reaction conditions, simple operation, high yield, low production cost, safe reaction and environmental protection, and can realize industrialized production.

Technical scheme of the present invention is:

The synthetic method of watermelon ketone comprises the following steps:

(1) Under nitrogen protection, add sodium carbonate solution with a mass concentration of 40-50 % to the reactor, under nitrogen protection, add 4-methylcatechol, heat up to 60-80°C for 1-2 hours, and then Add toluene to the reactor, heat and evaporate under normal pressure to take out the moisture in the material;

(2) Add organic amine and ammonium iodide to the material in step (1), then add dropwise 1,3-dichloroacetone and alcohol or a mixed solution of 1,3-dichloroacetone and butanone at 60-80°C, After dripping, heat-preserve and reflux for 3-5 hours; cool and filter with suction to obtain the crude product, which is removed from alcohol, butanone, and toluene under negative pressure conditions;

(3) Wash the crude product in step (2) with sodium sulfate solution to remove alcohol, butanone, and toluene to neutrality, then distill under reduced pressure, and recrystallize the fraction with a mixed solvent of acetone and n-hexane to obtain watermelon as a white crystalline solid ketone.

The molar ratio of 4-methylcatechol to 1,3-dichloroacetone is 1:0.9~1.05, the molar ratio of sodium carbonate to 4-methylcatechol is 1:0.4~0.5, ammonium iodide The molar ratio to 4-methylcatechol is 1:10.0~7.5, and the molar ratio of organic amine to ammonium iodide is 1:0.8~2.

The volume ratio of acetone and n-hexane in the mixed solvent is 1:1-1.5, and the volume ratio of the mixed solvent to the fraction is 1-3:1.

The mass ratio of 1,3-dichloroacetone to alcohol is 1:4~10, and the mixed mass ratio of 1,3-dichloroacetone to butanone is 1:4~7. Described alcohol is methanol or ethanol.

Said adding toluene to the material in step (1), the volume ratio of sodium carbonate solution to toluene is 1:1.5-3.

The organic amine is diethylamine or triethylamine.

The chemical reaction equation is as follows:

Compared with the prior art, the present invention has the following obvious advantages:

The reaction conditions of the present invention are that the reaction is performed at a relatively low temperature, there are many solvents, the temperature control in the reaction process is simple, and the recovered reaction water can be recovered and continued to be used. It can be seen from the equation that, by adopting the present invention, the material selectivity is relatively high in the reaction process, the by-products are few, the reaction loss is reduced, and the production cost is correspondingly reduced.

Detailed ways

Below in conjunction with specific example, further describe the present invention in detail. It should be understood that these examples are only for illustration of the present invention, but not to limit the scope of the present invention in any way.

Example 1

In the 2000ml four-necked round bottom flask that thermometer, reflux condenser, water trap, agitator are equipped with, add mass concentration and be 50% sodium carbonate solution 440g, under nitrogen protection, add 124g4-methylcatechol, be warming up to React at 60-80°C for 1-2 hours, add 800ml of toluene to heat and evaporate to take away the moisture in the material;

When no moisture is evaporated out of the material, the temperature of the material is lowered to 60°C, 5g of triethylamine and 14g of ammonium iodide are added in sequence, and a mixed solution of 130g of 1,3-dichloroacetone and 300ml of ethanol is slowly added dropwise, and the temperature is continued after the drop is completed. Reflux reaction for 3-5 hours; during the reaction process, take samples for GC analysis, stop the reaction when the 1,3-dichloroacetone is less than 0.01%, cool down, filter with suction to obtain the crude product, then remove the ethanol and toluene from the crude product under negative pressure conditions, Obtain the precipitation crude product 180g, the watermelon ketone content is 95% in the precipitation crude product;

Wash with sodium sulfate solution until neutral, distill under reduced pressure, collect 153 grams of watermelon ketone fraction, and use 200ml of 1:1 mixed solvent of acetone and n-hexane for secondary crystallization to obtain 145 grams of white crystal watermelon ketone, content 98.5%. The yield was 80.2%.

Example 2

In a 2000ml four-necked round-bottomed flask equipped with a thermometer, a reflux condenser, a water separator, and an agitator, add a mass concentration of 460g of a 50% sodium carbonate solution, under nitrogen protection, add 124g of 4-methylcatechol, and control the temperature at 60 React at ~80°C for 1-2 hours, add 800ml of toluene to heat and evaporate to take away the moisture in the material;

When no moisture is evaporated out of the material, the temperature of the material is lowered to 60°C, .8g of diethylamine and 15g of ammonium iodide are added in sequence, and a mixed solution of 120g of 1,3-dichloroacetone and 300ml of butanone is slowly added dropwise, and the dropwise Afterwards, continue to insulate and reflux for 3-5 hours; during the reaction process, take samples for GC analysis, stop the reaction when the 1,3-dichloroacetone is less than 0.01%, cool, and filter the crude product, and then remove the butylated product from the crude product under negative pressure conditions. Ketone, toluene, receive 175g of stripping crude product, content is 96%;

Wash with sodium sulfate solution until neutral, distill under reduced pressure, collect 150 grams of watermelon ketone fraction, and use 200ml of 1:1.3 mixed solvent of acetone and n-hexane for secondary crystallization to obtain 142 grams of white crystal watermelon ketone, content 99.2%. The yield was 83.3%.

Example 3

In a 2000ml four-necked round-bottomed flask equipped with a thermometer, a reflux condenser, a water separator, and an agitator, add a mass concentration of 480g of a 50% sodium carbonate solution, nitrogen protection, add 124g of 4-methylcatechol, and control the temperature at 60 React at ~80°C for 1-2 hours, add 800ml of toluene to heat and evaporate to take away the moisture in the material;

When no moisture is evaporated out of the material, the temperature of the material is lowered to 60°C, 10g of triethylamine and 17g of ammonium iodide are added in sequence, and a mixed solution of 126g of 1,3-dichloroacetone and 500ml of butanone is slowly added dropwise. Continue heat preservation and reflux reaction for 3-5 hours; take samples for GC analysis during the reaction process, stop the reaction when the 1,3-dichloroacetone is less than 0.01%, cool, and filter the crude product, and then remove the butanone from the crude product under negative pressure , toluene, receive the crude product 183g, the content is 95.5%; wash with sodium sulfate solution to neutrality, distill under reduced pressure, collect 155 grams of watermelon ketone fractions, and the fractions use 200ml 1:1.5 acetone and n-hexane mixed solvent for the second time Crystallize to obtain 142 grams of white crystalline watermelon ketone, with a content of 99.3%, and a yield of 79.2%.

Claims (5)

1. a synthetic method of watermelon ketone, is characterized in that comprising the following steps: (1) Under nitrogen protection, add sodium carbonate solution with a mass concentration of 40-50% to the reactor, under nitrogen protection, add 4-methylcatechol, heat up to 60-80°C for 1-2 hours, and then Add toluene to the reactor, heat and evaporate under normal pressure to take out the moisture in the material; (2) Add organic amine and ammonium iodide to the material in step (1), then add dropwise 1,3-dichloroacetone and alcohol or a mixed solution of 1,3-dichloroacetone and butanone at 60-80°C, After dripping, heat-preserve and reflux for 3-5 hours; cool and filter with suction to obtain the crude product, which is removed from alcohol, butanone, and toluene under negative pressure conditions; (3) Wash the crude product in step (2) with sodium sulfate solution to remove alcohol, butanone, and toluene to neutrality, then distill under reduced pressure, and recrystallize the fraction with a mixed solvent of acetone and n-hexane to obtain watermelon as a white crystalline solid ketone; The mass ratio of 1,3-dichloroacetone to alcohol is 1:4~10, and the mixed mass ratio of 1,3-dichloroacetone to butanone is 1:4~7; Said adding toluene to the material in step (1), the volume ratio of sodium carbonate solution to toluene is 1:1.5-3. 2. the synthetic method of a kind of watermelon ketone as claimed in claim 1 is characterized in that: the mol ratio of 4-methylcatechol and 1,3-dichloroacetone is 1: 0.9～1.05, sodium carbonate and The molar ratio of 4-methylcatechol is 1:0.4～0.5, the molar ratio of ammonium iodide and 4-methylcatechol is 1:10.0～7.5, and the molar ratio of organic amine and ammonium iodide is 1 :0.8～2. 3. the synthetic method of a kind of watermelon ketone as claimed in claim 1 is characterized in that: the volume ratio of acetone and n-hexane in the mixed solvent is 1:1～1.5, and the volume ratio of described mixed solvent and distillate is 1 ~3:1. 4. the synthetic method of a kind of watermelon ketone as claimed in claim 1, is characterized in that: described alcohol is methyl alcohol or ethanol. 5. the synthetic method of a kind of watermelon ketone according to claim 1 and 2, is characterized in that: organic amine is diethylamine or triethylamine.