KR19990084281A - Synthesis method of alpha-alkylperfuryl alcohol - Google Patents

Abstract

The present invention is to provide a method for synthesizing alpha-alkylperfuryl alcohol, which is superior in terms of purity and yield of the product and commercialized, compared to the conventional method for synthesizing alpha-alkylperfuryl alcohol.

In the alpha-alkylperfuryl alcohol of the present invention, magnesium and alkyl chloride are reacted in the presence of a solvent and an initiator to prepare an alkylmagnesium chloride as a Grignard reagent, which is reacted with perfural and Grignard and then added dropwise to an aqueous acid solution to hydrolysis. The reaction is carried out, followed by synthesis of solvent extraction, neutralization and solvent removal.

The synthesis method of the present invention can increase the yield to about 94 to 98%, and the purity of the final product can be obtained at about 98% or more.

Description

Synthesis method of alpha-alkylperfuryl alcohol

The present invention relates to a method for synthesizing alpha-alkylperfuryl alcohol represented by the following structural formula (I).

(I)

In the above formula, R is a methyl group or an ethyl group.

Tetrarahedron Letters No. 17, 1363-1364 (1976) shows a yield of 88% for the synthesis of alpha-ethylperfuryl alcohol, a detailed process description is not described. See also Perfumer Flavorist Vol. According to 17, 29-31 (1992), an improved Grignard reaction process was performed by simultaneously dropping alkyl bromide, which is more reactive than the two reactants, perfural and alkyl chloride, onto magnesium suspension. It is only 85%.

In addition, US Patent No. 4,352,756 describes the synthesis of perfuryl alcohol, but examples of using alkyl halides having 4 or more carbon atoms as reactants, and alpha having 2 carbon atoms, ethyl chloride, ethyl bromide and ethyl iodine as reactants. A synthesis example for ethylperfuryl alcohol is not shown.

In addition, US Pat. No. 4,536,349 discloses a synthesis method for alpha-methylperfuryl alcohol, but the purity is about 90% and the yield is not known.

Alpha-alkylperfuryl alcohols are known as intermediates of furan derivatives used as fragrances or flavor enhancers.

It is an object of the present invention to provide a method for synthesizing alpha-alkylperfuryl alcohol, which is superior in terms of purity and yield of a product and commercialized, as compared to conventional alpha-alkylperfuryl alcohol synthesis methods.

1 is a block diagram illustrating a method for synthesizing alpha-alkylperfuryl alcohol according to the present invention.

Alpha-alkylperfuryl alcohol represented by the structural formula (I) of the present invention,

Reacting magnesium and alkyl chloride in the presence of a solvent to prepare an alkylmagnesium chloride which is a Grignard reagent;

Reacting the alkyl magnesium chloride with furfural and Grignard;

Performing a hydrolysis reaction by dropping the reaction solution into an acid aqueous solution; And

The hydrolysis reaction solution is characterized in that it is prepared by performing a solvent extraction, neutralization and solvent removal process.

Hereinafter, the present invention will be described in detail.

In the method for synthesizing the alpha-alkylperfuryl alcohol of the present invention, magnesium used in preparing the Grignard reagent is mainly used in a turning type, and the amount of the magnesium is used in the range of 1 to 20 wt. It is preferable that the 3 to 15 weight ratio is most suitable in consideration of economical efficiency and process safety. When magnesium is used in an amount less than 1 weight ratio, the economical efficiency is lowered due to lower productivity. On the contrary, when magnesium is used in an amount exceeding 20 weight ratio, it is very disadvantageous in terms of process safety.

The solvents are ethers, for example diethyl ether, dipropyl ether, dibutyl ether, tetrahydrofuran (THF) or developed by Ferro, which is introduced in US Pat. No. 5,368,670 for stability. Diglyme and the like can be used.

The smaller the water content of the solvent used in the present invention, the better, but preferably 5 to 1,000 ppm. When the water content exceeds the above range, not only is it not well initiated by the reaction initiator, but also causes side reactions, leading to a decrease in yield. In addition, when the alkyl halide is added in a state where the reaction is not well initiated, the reaction rate is slower than this addition rate. Thus, unreacted alkyl halide having a low boiling point accumulates in the solvent, causing the reaction solution to boil at a temperature lower than the desired reaction temperature. Will occur.

In the process of the present invention, in preparing the Grignard reagent, the reactant may be an alkyl chloride belonging to the alkyl halide, for example methyl chloride or ethyl chloride, but in addition to the alkyl bromide or Alkyl Iodide etc. can also be used. Among the alkyl halides, alkyl iodine is low in economical efficiency, and alkyl chloride is often used because of low reactivity as a Grignard reagent. However, in the present invention, a low yield of alkyl chloride can be used to obtain a high yield. .

The alkyl chloride may be injected into the reactant in gaseous or liquid state, the reaction temperature may be carried out at 30 to 70 ℃, preferably 50 to 66 ℃, the reaction pressure is carried out at atmospheric pressure to 2.0 atm.

If the reaction temperature is less than 30 ℃ reaction rate is too slow, if the reaction temperature exceeds 70 ℃ solvent evaporation is severe, causing problems in process safety. In addition, in order to shorten the reaction time, when the reaction is performed at a relatively high temperature, the amount of solvent evaporation is large, and the reaction system must be maintained at a high pressure.

When the above reaction is initiated, the exothermic reaction can be used to maintain the desired reaction temperature without heating or cooling. The end point of the reaction is when the residual magnesium is not visually confirmed.

Since this reaction is exothermic, the evaporated solvent is condensed in a reflux condenser to reflux into the reactor. Note that the reaction is sensitive to moisture, so the reaction system must be disconnected from air.

The scheme can be written as follows.

Mg / solvent + RCl + initiator → RMgCl / solvent ----------- (2)

Wherein R is methyl or ethyl.

The surface of magnesium used as a raw material in the present invention is covered with a magnesium oxide layer having no reaction activity, so that even if alkyl chloride is injected, the reaction does not proceed well. The initiator is used in the present invention to activate the magnesium by removing the magnesium oxide layer of the magnesium surface. The initiators are Grignard reagents such as iodine, bromine, ethyl bromine, 1, 2-dibromoethane, methyl iodine, ethyl iodine, methyl magnesium bromide solution, ethyl magnesium bromide solution, ethyl magnesium chloride solution and methyl magnesium chloride solution. It can select and use 1 or more types. In particular, when the Grignard reagent is used as an initiator of the Grignard reagent manufacturing reaction, there is an advantage that the cost reduction effect can be brought. The amount of initiator used in the present invention is preferably 0.1 to 10.0 mol%, particularly 0.3 to 5.0 mol% relative to magnesium. Here, if it is less than 0.1 mol%, it will not start well, and if it exceeds 10 mol%, since it will inject more than necessary amount, it is unpreferable.

The following process is for the Grignard reaction, which is represented by the following scheme.

RMgCl / solvent + → / Solvent ---- (3)

Wherein R is methyl or ethyl.

This reaction is carried out in a typical batch (SBR type) in which a drop of Furfural is added dropwise to an alkylmagnesium chloride (RMgCl) solution. The reaction itself proceeds quickly and the reaction temperature starts at room temperature and is raised by the heat of reaction. Since Grignard reagents are sensitive to moisture, the reaction system is recommended to be run under a nitrogen atmosphere shielded from air.

The amount of perfural used is preferably 90 to 100 mol%, more preferably 93 to 98 mol% based on the magnesium.

As the solvent, it is not easy to remove water from the solvent recovered for reuse when tetrahydrofuran is used. Toluene, benzene, xylene or a combination thereof may be used for the solvent used up to the Grignard reaction to recover the solvent at a low water content. Substitute the solution for hydrolysis. The solvent thus replaced can be used again by distillation purification after the phase separation process.

The following process is represented by the reaction formula in the hydrolysis reaction is as follows.

/menstruum -----------(4)

In which R is methyl or ethyl.

The hydrolysis reaction is obtained by reacting R-O-MgCl formed in the Grignard reaction with R'OH which is a proton-donating reagent. In terms of the method of carrying out the reaction, there may be several cases. However, in the case of the reaction, a method of dropping an acid solution in a solvent layer containing RO-MgCl causes a problem of forming a solid mass of a load. It is hard to become a commercialization process. Therefore, in the present invention, on the contrary, the reaction is performed by dropping a solvent layer containing R-O-MgCl in an acid aqueous solution. The acid aqueous solution used here is hydrochloric acid, sulfuric acid, acetic acid or ammonium chloride, the amount of which is used is preferably 0.8 to 5.0 mol%, preferably 0.9 to 3.0 mol% with respect to magnesium, the reaction temperature is 20 to 80 ℃, preferably Is 30-60 degreeC.

The amount of the acid aqueous solution is sufficient to cause hydrolysis through a slight excess input, and is excessively wasteful. It is carried out at a slightly elevated temperature to increase the hydrolysis efficiency.

The next steps include extraction, neutralization and solvent extraction removal.

The reaction solution prepared in the above step is composed of an aqueous layer and a solvent layer, so that alpha-alkylperfural alcohol coexists in both layers, so that the separated aqueous layer is used as a solvent to minimize the loss to the aqueous layer after the first layer separation. Extract one more time. The temperature at the time of extraction is preferably performed in the range of room temperature to 40 ℃.

When the solvent is used as tetrahydrofuran, since pure tetrohydrofuran and water are originally mixed, the layer separation is not performed, but the aqueous layer contains magnesium salt formed as a result of hydrolysis, thereby forming layer separation. However, the separated solvent layer contains not only the synthesized alpha-alkylperfuryl alcohol but also acetic acid, so that a process of neutralizing using an aqueous solution of caustic soda, aqueous solution of caustic, aqueous solution of sodium carbonate, aqueous ammonia or a combination thereof is required. .

When the solvent is distilled off from the neutralized solvent layer, high purity alpha-alkylperfuryl alcohol of about 98% or more is obtained.

Structural analysis of alpha-alkylperfuryl alcohol can be confirmed by NMR, and purity analysis can use GC. The water content in the product and solvent can be measured by Karl Fisher method.

A schematic block diagram of the synthesis of the alpha-alkylperfuryl alcohol according to the present invention described above is shown in FIG. 1.

Hereinafter, the present invention will be described in more detail with reference to Examples.

Example 1

Nitrogen was charged in a 1 L round flask reactor dried to remove sufficient water, and 19.17 g of magnesium turning and 400 ml of anhydrous tetrahydrofuran were added. The solution was gently stirred and heated to about 40 DEG C. 3.0 mol of pre-prepared ethyl magnesium chloride. 10 ml of the solution was added. After the initiator was added, the reaction was confirmed by the heat generated and the color change of the reaction solution. The time required was about 15 minutes. The reaction temperature was maintained at 45-66 ° C. while ethyl chloride was introduced into the reaction solution over about 3 hours under vigorous stirring.

After completion of the reaction, 115.3 g of perfural was added dropwise over about 30 minutes through a dropping funnel, and the reaction temperature was maintained at 50 to 60 ° C. After the completion of dropping, the mixture was aged with stirring for about 1 hour for sufficient reaction and the reaction was terminated.

Thereafter, 460 g of a 20 wt% acetic acid solution was added to another 2 L round flask reactor, and the reaction solution filled in the dropping funnel was added dropwise over about 2 hours while stirring. At this time, the reaction temperature started at room temperature, and naturally warmed by the heat of reaction itself, and finally maintained at 60 ° C., and the dropping was completed and maintained at this temperature and aged under stirring for about 30 minutes.

The hydrolyzed reaction solution was separated through a separatory funnel to separate the tetrahydrofuran layer. The separated aqueous layer was added to the reactor again, 200 ml of tetrahydrofuran was added thereto, the temperature was raised to 30 to 50 ° C, extracted under strong stirring, and the tetrahydrofuran layer was separated again. The two separated tetrahydrofuran layers were collected and neutralized with 80 g of 20% by weight sodium carbonate solution, and then the salts formed were removed. Removal was carried out to obtain 147.5 g of alpha-ethylperfuryl alcohol having a purity of 99%. The yield at this time was 98.4%.

Example 2

Methyl chloride was used instead of ethylmagnesium chloride used as the initiator in Example 1, and methyl chloride was added instead of ethyl chloride. Thus obtained alpha-methylperfuryl alcohol had a purity of 99% and a yield of 95%.

Example 3

In Example 1, the same procedure as in Example 1 was carried out except that the magnesium turning amount was added as 14.5 g. The purity of the alpha-ethylperfuryl alcohol thus obtained was 98.3% and the yield was 94.7%.

Example 4

In Example 1, the same procedure as in Example 1 was carried out except that the magnesium turning amount was added as 58.3 g. The purity of the alpha-ethylperfuryl alcohol thus obtained was 98.1%, and the yield was 94.2%.

Example 5

In Example 1, 280g of 20 wt% hydrochloric acid was added instead of acetic acid, and hydrolysis was performed in the same manner as in Example 1. The purity of the alpha-ethylperfuryl alcohol thus obtained was 98.2% and the yield was 96.4%.

Comparative Example 1

After completion of the Grignard reaction in Example 1, the same procedure as in Example 1 was carried out except that tetrahydrofuran was replaced with 400 ml of toluene. The purity of the alpha-ethylperfuryl alcohol thus obtained was 90.3% and the yield was 85.0%.

Comparative Example 2

Example 1 was carried out in the same manner as in Example 1, except that the Grignard reagent was prepared without using an initiator. As a result, the reaction proceeded very slowly and reacted only about 25% of the added magnesium even after 10 hours of reaction.

Comparative Example 3

Example 1 was carried out in the same manner as in Example 1, except that acetic acid solution was added dropwise to the solution in which ethyl magnesium chloride and perfural were reacted during hydrolysis. As a result, a loaded solid mass formed, making stirring impossible.

The method for synthesizing the alpha-alkylperfuryl alcohol of the present invention is a process developed from a technical and economical point of view to be commercially advantageous, and the yield in the existing patent or literature is about 85 to 88%, Yield by the method is about 94 to 98%, the purity of the final product is about 98% or more can be used as a raw material of high purity that does not require any further purification. In addition, since the Grignard reagent itself can be used as an initiator when preparing Grignard reagent, a cost reduction effect can also be obtained.

Claims (8)

In the method for synthesizing alpha-alkylperfuryl alcohol, Reacting magnesium with alkylchloride in the presence of a tetrahydrofuran solvent and an initiator to prepare an alkylmagnesium chloride which is a Grignard reagent; Reacting the alkyl magnesium chloride with furfural and Grignard; Performing a hydrolysis reaction by dropping the reaction solution into an acid aqueous solution; And Method for synthesizing alpha-alkylperfuryl alcohol represented by the following structural formula (I), characterized in that it comprises the steps of performing a conventional solvent extraction, neutralization and solvent removal process for the hydrolysis reaction solution. (I) Wherein R is methyl or ethyl. The method for synthesizing alpha-alkylperfuryl alcohol according to claim 1, wherein the water content of the tetrahydrofuran solvent is 5 to 1000 ppm or less. The method of claim 1, wherein the initiator is iodine, bromine, ethyl bromine, 1, 2-dibromoethane, methyl iodine, ethyl iodine, methyl magnesium bromide solution, ethyl magnesium bromide solution, ethyl magnesium chloride solution and methyl magnesium chloride solution A method for synthesizing alpha-alkylperfuryl alcohol, characterized in that at least one selected from the group is used. The method of claim 1, wherein the amount of the initiator is used in an amount of 0.1 to 10.0 mol% based on magnesium. The method of claim 1, wherein the magnesium is used for the synthesis of alpha-alkylperfuryl alcohol, characterized in that 3 to 15% by weight based on the solvent. The method of claim 1, wherein the reactant of the alkyl chloride is injected into a liquid state or a gaseous state. The method for synthesizing alpha-alkylperfuryl alcohol according to claim 1, wherein the tetrahydrofuran solvent is replaced with benzene, toluene, xylene or a mixture thereof immediately after the Grignard reaction. The method of claim 1, wherein the acid aqueous solution is hydrochloric acid, sulfuric acid, acetic acid, ammonium chloride or a combination thereof.