阅读说明：本技术 一种制备甲基庚烯酮的方法 (Method for preparing methylheptenone ) 是由 沈稳 黄文学 于斌成 谢硕 张永振 黎源 于 2019-11-27 设计创作，主要内容包括：本发明公开了一种制备甲基庚烯酮的方法,在铑催化剂、碱和任选的助剂作用下3-甲基-2-丁烯-1-醇和丙酮发生选择性脱氢偶联反应,得到甲基庚烯酮。与现有工艺相比,本发明方法采用廉价易得的3-甲基-2-丁烯-1-醇和丙酮为原料,经一步反应制备了高附加值的甲基庚烯酮,该方法原子利用率高、三废少、条件温和,特别是选择性和收率高。(The invention discloses a method for preparing methyl heptenone, which comprises the step of carrying out selective dehydrogenation coupling reaction on 3-methyl-2-butene-1-alcohol and acetone under the action of a rhodium catalyst, alkali and an optional auxiliary agent to obtain the methyl heptenone. Compared with the prior art, the method adopts cheap and easily-obtained 3-methyl-2-butene-1-ol and acetone as raw materials to prepare the methyl heptenone with high added value through one-step reaction, and has the advantages of high atom utilization rate, less three wastes, mild conditions, and particularly high selectivity and yield.)

1. A method for preparing methyl heptenone is characterized in that 3-methyl-2-butene-1-alcohol and acetone are subjected to selective dehydrogenation coupling reaction under the action of a rhodium catalyst, alkali and an optional auxiliary agent to obtain the methyl heptenone.

2. The process according to claim 1, characterized in that the molar ratio of acetone to 3-methyl-2-buten-1-ol is 2-20:1, preferably 4-6: 1.

3. The process according to any one of the preceding claims, wherein the rhodium catalyst is used in a molar amount of from 0.01% to 0.1%, preferably from 0.01% to 0.02%, based on the molar amount of 3-methyl-2-buten-1-ol.

4. The process according to any one of the preceding claims, wherein the rhodium catalyst is [ Rh (COD) ]₂]OTf、[Rh(COD)(acac)]、[Rh(COD)₂]BF₄、[RhCl(COD)]₂、[Rh(NBD)₂]BF₄、[Rh(CO)₂(acac)]And [ RhH (CO) (PPh)₃)₃]One or more of (a).

5. The process according to any of the preceding claims, characterized in that the base is used in a molar amount of 0.1% to 1.0%, preferably 0.2% to 0.5% of the molar amount of 3-methyl-2-buten-1-ol.

6. The method of any one of the preceding claims, wherein the base is one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, tetramethylammonium hydroxide, and barium hydroxide.

7. The process according to any one of the preceding claims, characterized in that the auxiliary agent is used in a molar amount of 0 to 0.1%, preferably 0 to 0.01% of the molar amount of 3-methyl-2-buten-1-ol.

8. The method according to any one of the preceding claims, wherein the auxiliary agent is one or more of pyridine, pyrazine, quinoline, quinoxaline and C1-C4 alkyl mono-or poly-substituted pyridine, substituted isoquinoline, substituted quinoline and substituted quinoxaline.

9. The process according to any of the preceding claims, wherein the reaction temperature of the selective dehydrocoupling reaction is between 60 ℃ and 120 ℃; the reaction pressure is 0.5MPa-1.0MPa in terms of gauge pressure; the reaction time is 3-6 hours.

10. The method according to any one of the preceding claims, wherein, during the preparation, the alkali is added into a reaction kettle and replaced by nitrogen, then the rhodium catalyst, the optional auxiliary agent, the 3-methyl-2-butylene-1-alcohol and the acetone are mixed and added into the reaction kettle under the nitrogen atmosphere, the temperature is raised by stirring to carry out the selective dehydrogenation coupling reaction, and the reaction is terminated after the temperature is kept; the reaction solution was distilled to recover acetone, phase separation was performed, and the organic phase obtained by separation was distilled under reduced pressure to obtain methylheptenone.

Technical Field

The invention belongs to the field of organic synthesis, and particularly relates to a method for preparing methylheptenone from 3-methyl-2-butene-1-ol and acetone through selective dehydrogenation coupling reaction.

Background

Methyl heptenone with chemical name of 6-methyl-5-hepten-2-one and molecular formula of C₈H₁₄O, colorless or pale yellow liquid, with lemon grass, isobutyl acetate and fresh fruitThe aroma is edible essence which is allowed to be used by national standard and can be used for preparing essences of bananas, pears and berries; in addition, methylheptenone is a very important synthetic intermediate, and can be used for synthesizing linalool, citral, pseudoionone and other flavors, and the latter can be used for further preparing vitamin A, vitamin E, vitamin K1, various flavors and the like. The methyl heptenone has vigorous market demand at present, and with the deepening of the application development of the methyl heptenone, the application range of the methyl heptenone is further expanded, and the demand is greatly increased. Therefore, the method has important significance for enhancing the technical research on the synthesis of the methylheptenone. The existing method for preparing methyl heptenone mainly comprises an acetylene-acetone method, an isobutene-formaldehyde method, an isoprene method, a Saucy-Marbet method and the like.

The acetylene-acetone process is the earliest industrial process for methylheptenone (see DE2126356, GB788301, GB888999, DE1137433, CN1218792A, etc.), which uses acetone as a starting material, and uses acetylene to perform addition reaction on acetone to obtain an alkynol intermediate, and then partial hydrogenation is performed to obtain an allyl alcohol intermediate, and the allyl alcohol intermediate and ethyl acetoacetate undergo a carol rearrangement reaction to obtain a methylheptenone product, wherein the reaction route is as follows:

the route needs to consume a large amount of calcium carbide to generate acetylene and generate a large amount of calcium carbide waste residues, equivalent ethanol byproducts can be generated by the carrot reaction, the atom economy of the synthetic route is poor, and the three wastes are more.

The isoprene method is characterized in that isoprene is used as a starting material and is added by utilizing hydrogen chloride to obtain isopentenyl chloride, and then the isopentenyl chloride is condensed with acetone to obtain a methyl heptenone product. The main difficulty of the current route is condensation reaction, the current literature reports that phase transfer catalysis methods are adopted (see JP40-22251, JP56-115734, JP56-61319, CN1762955A, CN1772722A and CN103664556A), and the selection of a proper phase transfer catalyst is the key of the condensation reaction of chloroisoamylene and acetone, and the reaction route is as follows:

the technology generally has an obvious defect of recycling the catalyst. In summary, the methyl heptenone prepared by the isoprene method has poor selectivity, general yield, large amount of three wastes, difficult phase transfer catalyst recovery and difficult industrial production, and the process is eliminated at present.

Basf in its patent reports the one-pot synthesis of 6-methyl-6-hepten-2-one from isobutylene, formaldehyde and acetone, and the hydroisomerization of the resulting product to methyl heptenone (see DE1277848B, DE1267682B, the reaction scheme is as follows:

although the synthetic route is short, the reaction conditions in the first step are harsh, high temperature and high pressure are required, the reaction selectivity is poor (40-50% of product selectivity), a large amount of byproducts are generated, and the rectification and purification of the product are difficult.

The method for preparing methyl heptenone by the Saucy-Marbet method takes methyl butenol and methoxypropene as raw materials to perform Saucy-Marbet rearrangement reaction under the action of an acid catalyst to prepare methyl heptenone (see DE1193490, DE19649564, CN1539807A, CN1914143, CN108299171A, CN1228757 and CN102197014), and the reaction route is as follows:

the method for preparing methyl heptenone by the Saucy-Marbet method has high atom utilization rate and is environment-friendly, but the raw material of the methoxypropene is easy to hydrolyze and has low boiling point and harsh requirements on reaction conditions, and an acid catalyst is used, so that the requirements on equipment materials are high. Meanwhile, the raw materials of 2-methyl-3-butylene-2-alcohol and 2-methoxypropene are prepared by two-step reaction and are not easy to obtain, so that the industrial application is limited.

In conclusion, although methyl heptenone is synthesized by a plurality of methods at present, and a part of synthetic routes have been produced on a large scale, the synthetic routes generally have the defects of more three wastes, complex side reaction, difficult product purification and the like; therefore, a new methyl heptenone synthesis route is still needed to be developed, the defects of the existing route are overcome, and the methyl heptenone product is synthesized more efficiently, environmentally and economically, especially the methyl heptenone product is synthesized with high conversion rate and selectivity.

Disclosure of Invention

In view of the problems in the prior art, the present invention provides a method for synthesizing methylheptenone from 3-methyl-2-buten-1-ol. The method overcomes the defects of more three wastes, complex side reaction, difficult product purification and the like of the method for synthesizing the methyl heptenone in the prior art, can synthesize the methyl heptenone product more efficiently, environmentally and economically, and particularly has high selectivity and high yield.

In order to achieve the purpose, the invention adopts the following technical scheme:

a process for the preparation of methylheptenone which involves selective dehydrocoupling of 3-methyl-2-buten-1-ol and acetone as starting materials in the presence of a rhodium catalyst, a base and optionally an auxiliary to give methylheptenone:

in a particular embodiment of the invention, the molar ratio of acetone to 3-methyl-2-buten-1-ol is from 2 to 20:1, such as 5:1, 10:1 or 15:1, preferably from 4 to 6: 1.

In a specific embodiment of the invention, the rhodium catalyst is [ Rh (COD) ]₂]OTf、[Rh(COD)(acac)]、[Rh(COD)₂]BF₄、[RhCl(COD)]₂、[Rh(NBD)₂]BF₄、[Rh(CO)₂(acac)]And [ RhH (CO) (PPh)₃)₃]Preferably [ Rh (COD) ]₂OTf](ii) a The rhodium catalyst is used in a molar amount of 0.01% to 0.1%, such as 0.03%, 0.06% or more, based on the molar amount of 3-methyl-2-buten-1-ol0.08%, preferably 0.01-0.02%.

In a specific embodiment of the invention, the base is one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, tetramethylammonium hydroxide and barium hydroxide, preferably lithium hydroxide; the amount of base used is 0.1% to 1.0% by moles, such as 0.3%, 0.6% or 0.8%, preferably 0.2 to 0.5% of the molar amount of 3-methyl-2-buten-1-ol.

In a specific embodiment of the invention, the auxiliary agent is one or more of pyridine, isoquinoline, quinoline, quinoxaline and C1-C4 alkyl mono-or poly-substituted pyridine, substituted pyrazine, substituted quinoline and substituted quinoxaline, preferably quinoline, wherein the C1-C4 alkyl is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or the like; the auxiliaries are used in a molar amount of 0 to 0.1%, such as 0.001%, 0.008% or 0.05%, preferably 0 to 0.01%, based on the molar amount of 3-methyl-2-buten-1-ol.

In a particular embodiment of the invention, the reaction temperature of the selective dehydrocoupling reaction is between 60 ℃ and 120 ℃, for example 80 ℃; the reaction pressure is 0.5-1.0MPa (gauge pressure), for example, 0.4MPa nitrogen is filled in the reaction process; the reaction time is 3 to 6 hours, such as 4 or 5 hours.

In one embodiment of the present invention, the specific operation steps are, for example: adding alkali into the autoclave, and replacing with nitrogen for three times; in a glove box, mixing a rhodium catalyst, 3-methyl-2-butene-1-ol and acetone, adding the mixture into an autoclave in a nitrogen atmosphere, opening a heating and stirring device of the autoclave, keeping the temperature for a certain time, terminating the reaction, sampling, carrying out GC (gas chromatography) analysis, and determining the conversion rate and selectivity of the reaction by using an internal standard method. And distilling the reaction liquid to recover acetone, then carrying out phase separation, and carrying out reduced pressure distillation on an organic phase to obtain the methyl heptenone.

The mechanism of the selective dehydrocoupling reaction in the present invention is as follows: the rhodium catalyst activates (i.e. performs dehydrogenation reaction) 3-methyl-2-buten-1-ol to generate 3-methyl-2-butenal and [ RhH ] at the same time₂]A species; under the catalysis of alkali, the 3-methyl-2-butenal and acetone have aldol condensation reaction to produce 6-methyl-3, 5-heptadiene-2-a ketone and produces one molecule of water; due to steric hindrance, [ RhH₂]The species selectively hydrogenates the 3-position double bond of 6-methyl-3, 5-heptadiene-2-ketone to generate methyl heptenone. Further, addition of a certain amount of an auxiliary such as quinoline or other organic base can poison [ RhH₂]Species, reduces the hydrogenation activity, and is more beneficial to the selective hydrogenation of the 3-position double bond of the 6-methyl-3, 5-heptadiene-2-ketone. Meanwhile, organic bases such as quinoline and the like are added to be cooperatively catalyzed with inorganic bases, so that the aldol condensation reaction of the intermediate 3-methyl-2-butenal and acetone is facilitated, and the selectivity of the dehydrogenation coupling reaction is further improved.

Compared with the prior art, the invention has the following beneficial effects:

1. the cheap and easily-obtained 3-methyl-2-butene-1-ol and acetone are used as raw materials to prepare the methyl heptenone with high added value, the highest conversion rate of the raw material 3-methyl-2-butene-1-ol is 99%, and the highest selectivity of the product methyl heptenone relative to the 3-methyl-2-butene-1-ol is 98%.

2. The methyl heptenone is prepared by adopting a selective dehydrogenation coupling reaction one-step method, has high atom utilization rate, less three wastes and mild conditions, and has the potential of industrial amplification production.

Detailed Description

The process provided by the present invention is described in further detail below, but the present invention is not limited thereto.

Raw materials

3-methyl-2-buten-1-ol with the purity of 99 percent, and a Chinese catalyst Huabang;

acetone with purity higher than 99.5%, and Yiweiyuan chemical;

[Rh(COD)₂]OTf、[Rh(COD)(acac)]、[Rh(COD)₂]BF₄、[RhCl(COD)]₂、[Rh(NBD)₂]BF₄、[Rh(CO)₂(acac)]and [ RhH (CO) (PPh)₃)₃]The purity is more than 99 percent, and the sigma-aldrich is obtained;

pyridine, isoquinoline, quinoline, quinoxaline, purity 98%, avastin reagent;

sodium hydroxide, potassium hydroxide, anhydrous lithium hydroxide, tetramethyl ammonium hydroxide and barium hydroxide, the purity is more than 98 percent, and the west longa science is adopted;

acetonitrile, HPLC, science of julonga;

test instrument and calculation method

(1) Gas chromatography test conditions adopted by the invention

The instrument model is as follows: agilent 7890B;

sample introduction volume: 1 microliter;

sample inlet temperature: 280 ℃; pressure: 12.659 psi; total flow rate: 30 ml/min;

the split ratio is as follows: 30/1, respectively;

a chromatographic column: agilent DB-5(30 m.times.0.25 mm.times.0.25 μm);

flow rate of the chromatographic column: 2 ml/min; pressure: line speed at 8.51 psi: 33.3 cm/sec;

temperature rising procedure: the initial temperature is 40 ℃, the temperature is raised to 100 ℃ at the speed of 5 ℃/min, and the temperature is kept for 1 min; heating to 280 deg.C at a rate of 10 deg.C/min, and keeping for 5 min;

detector temperature: 300 ℃; air flow rate: 400 ml/min; hydrogen flow rate: 40 ml/min; nitrogen flow rate: 25 ml/min.

(2) The model of the nuclear magnetic resonance instrument adopted by the invention is a Bruker-400 nuclear magnetic resonance instrument, and the model of the mass spectrometer is a Bruker BIO TOF Q mass spectrometer.

(3) Method for calculating the conversion of 3-methyl-2-buten-1-ol and the selectivity of methylheptenone over 3-methyl-2-buten-1-ol:

conversion and selectivity were calculated using internal standard methods well known to those skilled in the art: selecting 2-heptanone as an internal standard substance, and dissolving the internal standard substance in acetonitrile to prepare internal standard mother liquor with the concentration of 1 wt%. Weighing 3-methyl-2-butene-1-ol and methyl heptenone (0.01-0.1 g) with gradient mass, then diluting with an equal amount of internal standard mother liquor (10g), and performing GC analysis to sequentially obtain GC peak area ratios corresponding to the mass ratios of the 3-methyl-2-butene-1-ol and the methyl heptenone to the internal standard. By taking the mass ratio as a horizontal coordinate and the peak area as a vertical coordinate, internal standard curves of the 3-methyl-2-butene-1-ol and the methyl heptenone can be respectively obtained, and the relationship between the mass ratio of the 3-methyl-2-butene-1-ol and the methyl heptenone to the internal standard and the GC peak area ratio can be obtained by performing linear fitting on the internal standard curves. When the reaction is subjected to sampling analysis, the mass of an internal standard is known, GC analysis can obtain the GC peak area ratio of the 3-methyl-2-buten-1-ol and the methyl heptenone to the internal standard, the mass of the 3-methyl-2-buten-1-ol and the methyl heptenone in a sample can be calculated according to the relationship between the mass ratio and the peak area ratio obtained by the internal standard method, and further the mass fractions of the 3-methyl-2-buten-1-ol and the methyl heptenone in a sampled reaction liquid can be obtained, so that the conversion rate of the 3-methyl-2-buten-1-ol and the selectivity of the methyl heptenone to the 3-methyl-2-buten-1-ol can be calculated.