WO2020140414A1

WO2020140414A1 - Method for preparing unsaturated ketone

Info

Publication number: WO2020140414A1
Application number: PCT/CN2019/095192
Authority: WO
Inventors: 黄高峰; 赵贺; 赵德胜; 严宏岳
Original assignee: 浙江新和成股份有限公司; 山东新和成维生素有限公司; 山东新和成药业有限公司
Priority date: 2019-01-02
Filing date: 2019-07-09
Publication date: 2020-07-09
Also published as: DE112019002562B4; CN109503342B; CN109503342A; DE112019002562T5

Abstract

Disclosed is a method for preparing an unsaturated ketone. In the method, an unsaturated alcohol and 2-alkoxy propylene are used as raw materials, and a Saucy-Marbet reaction is performed by modifying an acidic resin in a fixed bed, so as to synthesize an unsaturated ketone with high selectivity and high yield. The method uses a modified acidic resin as a catalyst to compensate for the poor catalytic effect of a conventional acidic resin, and uses a fixed bed reactor for the catalytic reaction, so that separation of the catalyst and a reaction product can be achieved before and after the reaction, thereby avoiding device corrosion and adverse effects on subsequent industrial treatment caused by the presence of a large amount of an acid. The method is an economical and efficient synthesis method.

Description

Method for preparing unsaturated ketone

Technical field

The invention belongs to the technical field of acid-catalyzed preparation of unsaturated ketones, and particularly relates to a method for preparing unsaturated ketones by carrying out the Saucy-Marbet reaction in a fixed-bed reactor using a modified solid acid as a catalyst.

Background technique

Unsaturated ketones are important starting materials for the synthesis of flavors, fragrances, and pharmaceutical intermediates, such as methyl heptenone, pseudoionone, etc. Because of the prominent position of this unsaturated ketone in the chemical industry, many scholars have made their synthesis methods A lot of research has been done. US6184420 provides an acid-catalyzed reaction method for the synthesis of unsaturated ketones from propargyl alcohol and ethers; CN98120681 provides a method for synthesizing γ and δ through the conventional reaction of allyl alcohol or propargyl alcohol with isopropenyl ether Monounsaturated/or β, γ, δ-bisunsaturated ketone method; CN200980142015.9 provides a tertiary vinyl methanol and isopropenyl methyl ether or isopropenyl ethyl in the presence of catalyst ammonium salt Preparation of γ, δ-unsaturated ketone by ether reaction.

The alkoxypropene method was first invented by Saucy and Marbet (1967, G. Saucy, R. Marbet, Helv. Chim. Acta 50 (1967) 2091-2095, US3029287), this method uses unsaturated alkynol and alkoxypropene as The raw materials, toluene, petroleum ether and halogenated hydrocarbons are used as solvents. Under the catalysis of acidic catalysts, high-yield synthetic unsaturated ketones with a yield of up to 90%. The disadvantage of this method is that the catalyst cannot be separated in the reaction system. The catalyst cannot be recycled, and it has been observed that the residual portion of the catalyst also affects the subsequent saturation hydrogenation selectivity of unsaturated ketones. The common treatment method is the reaction liquid after alkali neutralization and acid catalysis. US6380437 adopts sodium acetate in methanol solution to neutralize and hydrogenate after saturation, and the yield reaches 90%. US6586635 uses triethylamine to neutralize the acidic catalyst. After a series of post-treatments, Pd/C is saturated and hydrogenated, but there is a problem of poor hydrogenation activity. US5113021 introduces a method for neutralizing acid catalysts with sodium bicarbonate and sodium carbonate. The subsequent saturation hydrogenation process has not been described. To a certain extent, the neutralization method can solve the effect of the residual catalyst on the subsequent saturation hydrogenation selectivity, but it also has a greater influence on the saturation hydrogenation catalytic activity.

In general, the fixed bed catalytic reaction technology is more common in esterification reaction (see CN105154239A, CN101723828B, CN100392045C), cracking reaction (see CN106917163A, CN204509222U), there is no report in the process of catalyzing the Saucy-Marbet reaction, the disadvantage is that the conventional acid resin fixed bed Catalyze the Saucy-Marbet reaction. Due to the easy reaction of alkoxypropene with acid, the diffusion and mass transfer of propargyl alcohol in the pores of conventional resins is slow, resulting in the poor selectivity and yield of conventional acidic resin fixed-bed catalytic Saucy-Marbet reactions. low.

Summary of the invention

The invention provides a method for preparing unsaturated ketones. On the one hand, the preparation method improves the yield of the reaction and solves the problem of low yield catalyzed by conventional acid resins. On the other hand, it does not leave acid in the unsaturated ketone products. , To avoid the impact on the subsequent hydrogenation quality of unsaturated ketones.

The method for synthesizing the unsaturated ketone provided by the present invention is achieved by the following ways:

A method for preparing unsaturated ketones, in which unsaturated alcohol and 2-alkoxypropene are mixed, and the Saucy-Marbet reaction is carried out in a fixed bed reactor equipped with a modified acid resin to obtain the unsaturated ketone;

The modified acid resin is modified by tributylammonium chloride.

After the reaction is completed by the method, the neutralization can be performed to remove light and rectify to obtain an unsaturated ketone product, wherein the specific process parameters of the Saucy-Marbet reaction operation are described in patents such as CN98120681, CN200980142015.9, etc. Known in the industry.

Preferably, the specific steps of the acid resin modification treatment method are:

(1) Mix the acid resin and 99% methanol at a ratio of 1:3, wash at 50°C for 2-3 hours, acidify with a 30% hydrochloric acid solution for 1.0 hour, and finally replace residual water with methanol.

(2) Put the pre-treated acidic resin in the ultrasonic bath, add the modifier tributylalkylammonium chloride methanol solution to the acidic resin system, the concentration of tributylalkylamine chloride methanol solution is 0.5-4.0%, The mass ratio of the tributylalkanium chloride methanol solution to the acid resin is 1:1-6, the temperature is 20-80°C, and the treatment time is 0.5-2h. After the treatment is completed, transfer to the fixed bed.

Preferably, the structural formula of the tributylammonium chloride is as follows:

Among them, R is an alkyl group, and R is more preferably a C ₁ -C ₄ alkyl group.

Preferably, the concentration of the tributylalkylammonium chloride methanol solution is 1-1.5%.

Preferably, the mass ratio of the tributylammonium chloride methanol solution to the acid resin is 1:3-4.

Preferably, the modification temperature of the tributylammonium chloride methanol solution is 20-40°C.

Preferably, the acidic resin catalyst used is a strongly acidic cation exchange resin, which is specifically characterized as that the pore structure of the resin is macropores, the loaded acid is a strong acid, the surface area is 25-45m ² /g, and the pore size is

The exchange capacity is 0.8-4.5eq/L, and the tolerance temperature is ≥140℃.

In the present invention, the unsaturated ketone includes β, γ unsaturated ketone and/or β, δ unsaturated ketone; the structure of the β, γ unsaturated ketone is as shown in formula (I):

The structure of the β, δ unsaturated ketone is shown in formula (II):

R ₁ and R ₃ are alkyl groups of 1 to 2 carbon atoms, R ₂ and R ₄ are hydrocarbon groups of ₁ to 12 carbon atoms, and R ₂ is preferably an alkyl group of ₁ to 12 carbon atoms.

Among them, generally β, γ unsaturated ketones are the main products, but the subsequent hydrogenation reaction products of β, δ unsaturated ketones are the same, so there is no need to separate the two substances after the reaction.

The structural formula of the unsaturated alcohol is:

R ₅ is an alkyl group of 1-2 carbon atoms, R ₆ is a hydrocarbon group of 1-12 carbon atoms, and R ₆ is preferably an alkyl group of 1-12 carbon atoms.

The structural formula of the 2-alkoxypropene is:

Among them, R ₇ is an alkyl group, as a leaving group, generally a methyl group.

Preferably, the flow rate of the mixture through the fixed bed is 0.2-0.5 times the volume of the acid resin catalyst per hour.

Compared with the prior art, the beneficial effects of the present invention are as follows:

The preparation method adopts a fixed-bed reactor to realize the two-phase separation of the catalyst and the reaction raw materials. The reaction liquid does not need to consider the influence of the residual acid on the subsequent processing, and the crude unsaturated ketone can be obtained without neutralization, which solves the residual catalyst on the unsaturated ketone The impact of the subsequent hydrogenation quality; at the same time, the relatively stable and continuously used modified acid resin is used as a catalyst to solve the problem of low yield catalyzed by conventional acid resins.

BRIEF DESCRIPTION

Fig. 1 is a schematic diagram of the process flow of Saucy-Marbet reaction using a fixed bed in the present invention; in the figure, A: unsaturated alcohol; B: alkoxypropene; C: reaction solution; P1/P2: metering pump; T fixed bed .

detailed description

The present invention will be described in detail below with reference to examples, but the content of the present invention is not limited to these examples.

Example 1

The reaction was carried out according to the reaction scheme shown in Figure 1. The feed flow of dehydrogenated tert-alcohol and 2-methoxypropene was adjusted by a metering pump. The feed flow of dehydrogenated tert-alcohol was: 0.088 ml/s, 2 -The feed flow rate of methoxypropene is: 0.1ml/s, the filling volume of the acid resin in the fixed bed is 2.0L, the molar ratio of dehydrogenated nerolidol and 2-methoxypropene is 1:4, and it is fully mixed in the mixer Afterwards, it was preheated to 100℃ by external heat tracing and entered the acid resin bed from the top. The acid resin was macroporous acid resin modified by tributylmethylammonium chloride. The bed temperature was 120℃ and the residence time was 3h. The reaction liquid enters the material storage tank after passing through the condenser, and the discharge pipe is equipped with a sampling port, which can monitor the reaction in the fixed bed at any time. The apparent content of the reaction product is 93%, and the yield is 89%.

The reaction formula is as follows:

The modification method of macroporous acidic resin in this implementation is as follows:

(2) Place the pre-treated acidic resin in the ultrasonic bath, add the modifier tributylmethylammonium chloride methanol solution to the acidic resin system, the concentration of the tributylalkylamine chloride methanol solution is 2.5%, and the tributyl chloride The mass ratio of alkanolammonium methanol solution to acid resin is 1:3, the temperature is 60℃, and the treatment time is 1h. After the treatment is completed, transfer to the fixed bed.

The reaction liquid is saturated and hydrogenated after rectification. The specific operating parameters: 500 grams of rectified materials are loaded into a high-pressure reactor with a volume of 2L, the Pd/C catalyst feed ratio is 2‰ (wt%), and hydrogen is continuously introduced. The reaction temperature is 110 ℃, the pressure is 2MPa, the remaining 0.5% of the reactant is the end point of the hydrogenation reaction, and the reaction formula is:

Ten batches of Pd/C catalyst were applied, and the results are shown in Table 1.

Table 1

Comparative Example 1

Referring to Example 3 of US6586635, weigh 448 g of dehydrogenated nerol and 432 g of 2-methoxypropene, mix well, add 0.2% molar equivalent of methanesulfonic acid and acetone solution, and suck it into a 2L high-pressure reaction kettle under negative pressure to increase the temperature To 110 ℃, residence time 3h, sampling to detect the apparent content of the reaction product 92%, yield 90%. Then the low boiling point components, mainly excess 2-methoxypropene and 2,2-dimethoxypropane, are separated on a rotary thin-film evaporator and concentrated in a cold trap. The obtained 6,10,14-trimethyl-pentadeca-4,5-dien-2-one and 6,10,14-trimethylpentadecane-3,5-dien-2-one The mixture was saturated and hydrogenated after rectifying the reaction liquid with Pd/C catalyst for hydrogenation. The Pd/C catalyst was applied to ten batches. The results are shown in Table 2.

Table 2

Comparative Example 2

Adjust the feed flow of dehydrogenated nerolidol and 2-methoxypropene so that the dehydrogenated nerolidol and 2-methoxypropene are mixed in a molar ratio of 1:4, and after being thoroughly mixed through the mixer, use It is preheated to 100℃ by external heat tracing and enters the acid resin bed from the top. The acid resin is an unmodified conventional acid resin. The bed temperature is 120℃ and the residence time is 3h. The reaction liquid enters after passing through the condenser The material storage tank and the discharge pipe are equipped with sampling ports, which can monitor the reaction in the fixed bed at any time, and the yield of the reaction product is 71%.

The above experimental results show that the modified acidic resin of the present invention catalyzes the Saucy-Marbet reaction, compared with ordinary acidic resins, the yield is significantly improved, reaching the level of homogeneous catalyst methanesulfonic acid; Catalytic hydrogenation has an adverse effect and can maintain a higher activity of the hydrogenation catalyst.

Claims

A method for preparing unsaturated ketones, characterized in that unsaturated alcohol and 2-alkoxypropene are mixed, and the Saucy-Marbet reaction is carried out in a fixed-bed reactor equipped with a modified acidic resin to obtain the unsaturated ketone;

The modified acid resin is modified by tributylammonium chloride.
The method for preparing an unsaturated ketone according to claim 1, wherein the modified acid resin is obtained by the following method:

(1) Pretreatment: The acidic resin is washed with methanol, acidified with hydrochloric acid solution, and then the residual water is replaced with methanol;

(2) Modification: The modifier is added to the acid resin system, and the modification treatment is carried out under ultrasonic conditions;

The modifier is a methanol solution of tributylammonium chloride with a concentration of 0.5-4.0 wt%.
The method for preparing an unsaturated ketone according to claim 2, wherein the concentration of the methanol solution of tributylammonium chloride is 1-1.5%.
The method for preparing an unsaturated ketone according to claim 2, wherein the structural formula of the tributylammonium chloride is as follows:

Among them, R is an alkyl group.
The method for preparing an unsaturated ketone according to claim 2, characterized in that the mass ratio of the tributylammonium chloride methanol solution to the acid resin is 1:1-6, preferably 1:3-4 .
The method for preparing an unsaturated ketone according to claim 2, wherein the modification temperature is 20-80°C.
The method for preparing an unsaturated ketone according to claim 5, wherein the modification temperature is 20-40°C.
The method for preparing unsaturated ketones according to claim 2, characterized in that the acidic resin used is a strongly acidic cation exchange resin with a surface area of 25-45m 2 /g and a pore size of
The exchange capacity is 0.8-4.5eq/L, and the tolerance temperature is ≥140℃.
The method for preparing an unsaturated ketone according to any one of claims 1 to 8, wherein the unsaturated ketone comprises β, γ unsaturated ketone and/or β, δ unsaturated ketone;

The structure of the β, γ unsaturated ketone is shown in formula (I):

The structure of the β, δ unsaturated ketone is shown in formula (II):

R 1 and R 3 are alkyl groups of 1-2 carbon atoms, and R 2 and R 4 are hydrocarbon groups of 1-12 carbon atoms.
The method for preparing an unsaturated ketone according to claim 1, wherein the flow rate of the mixture through the fixed bed is 0.2-0.5 times the volume of the acid resin catalyst per hour.