CN116143601A - Synthesis method of cyclopropyl methyl ketone - Google Patents
Synthesis method of cyclopropyl methyl ketone Download PDFInfo
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- CN116143601A CN116143601A CN202310171823.XA CN202310171823A CN116143601A CN 116143601 A CN116143601 A CN 116143601A CN 202310171823 A CN202310171823 A CN 202310171823A CN 116143601 A CN116143601 A CN 116143601A
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- cyclopropyl methyl
- methyl ketone
- butyrolactone
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- C07—ORGANIC CHEMISTRY
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
- C07C45/82—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
- C07C45/59—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in five-membered rings
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
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Abstract
The invention discloses a method for synthesizing cyclopropyl methyl ketone, which comprises the following steps of S1, preparing raw material alpha-acetyl-gamma-butyrolactone; s2, hydrolyzing the alpha-acetyl-gamma-butyrolactone to obtain a cracking product; s3, decarboxylation and chlorination of a cracking product are carried out to obtain a crude cyclopropyl methyl ketone product; s4, carrying out fine distillation cyclization on the crude cyclopropyl methyl ketone, and separating impurities by adjusting the reflux ratio, thereby obtaining the high-purity cyclopropyl methyl ketone by distillation. The invention firstly needs to prepare the raw material alpha-acetyl-gamma-butyrolactone, thus ensuring the purity of the raw material by preparing the raw material, improving the purity of the raw material preparation by extracting and distilling in the subsequent process in the preparation process, ensuring the stable source of the raw material in the setting of the subsequent synthetic preparation, simultaneously omitting the impurity removal process in the subsequent synthetic preparation process, ensuring the more stable subsequent synthetic preparation process and ensuring the more definite and simple process.
Description
Technical Field
The invention relates to the field of organic chemical synthesis, in particular to a method for synthesizing cyclopropyl methyl ketone.
Background
Cyclopropyl methyl ketone is an important organic raw material and intermediate, has important roles in medicine and pesticide, and is mainly used for synthesizing the bactericides cyprodinil and cyproconazole in pesticide.
The synthesis method of the cyclopropyl methyl ketone is prepared by respectively carrying out acetylation, hydrolysis, decarboxylation, chlorination, cyclization and fine steaming on gamma-butyrolactone, and when the traditional synthesis process is used for synthesizing the cyclopropyl methyl ketone, the gamma-butyrolactone raw material is mostly obtained in a direct purchasing mode, so that the acquisition mode can increase the cost of purchasing the whole raw material, meanwhile, the purity of the raw material cannot be ensured in a direct gamma-butyrolactone raw material mode, the purity of substances in the subsequent synthesis process cannot be ensured, and the subsequent process needs to be additionally provided with a impurity removing step, so that the whole synthesis process is complicated.
Disclosure of Invention
The invention aims to provide a synthesis method of cyclopropyl methyl ketone, which aims to solve the problems in the background technology.
In order to achieve the above purpose, the present invention provides the following technical solutions: a method for synthesizing cyclopropyl methyl ketone, comprising the following steps of;
s1, preparing raw materials of alpha-acetyl-gamma-butyrolactone, acylating diketene and absolute ethyl alcohol under the catalysis of a catalyst to generate ethyl acetoacetate, condensing and ring-closing the product by adding the catalyst to generate sodium acetylbutyrolactone, acidifying with hydrochloric acid, extracting with benzene, and distilling to obtain the product;
s2, hydrolyzing the alpha-acetyl-gamma-butyrolactone, putting the prepared alpha-acetyl-gamma-butyrolactone into a catalytic reactor, filling nitrogen, heating, adding a catalyst for replacement cracking, and obtaining a cracking product;
s3, decarboxylation and chlorination of a cracking product are carried out, the cracking product is added into a jacketed reactor, then the temperature is raised, a mixed solvent of N-dimethylformamide and chlorobenzene is added into the jacketed reactor, and meanwhile, an inert solvent is added for reaction, so that a crude cyclopropyl methyl ketone product is obtained;
s4, carrying out distillation cyclization on the crude cyclopropyl methyl ketone, transferring the crude cyclopropyl methyl ketone into a rectifying tower, carrying out high-tower split flow, rectifying, and separating impurities by adjusting the reflux ratio to obtain high-purity cyclopropyl methyl ketone.
Preferably, the catalyst used for acylating the diketene and the absolute ethyl alcohol is sodium ethoxide, and the catalyst for condensing and closing the loop of the acetoacetate is ethylene oxide and sodium hydroxide.
Preferably, the temperature at which the α -acetyl- γ -butyrolactone hydrolysis process is heated is 120-140 ℃, and the moisture content of the nitrogen is 100ppm.
Preferably, the composition of the hydrolysis catalyst of the alpha-acetyl-gamma-butyrolactone comprises sodium iodide, potassium iodide, sodium bromide, potassium bromide, sodium chloride and potassium chloride.
Preferably, the particle size of the catalyst is 800-1000 micrometers, stirring is carried out at a rotating speed of 200r/min in the hydrolysis catalysis process, the stirring time is 3-5h, and stirring is carried out at intervals of 3-5min after each stirring time is 15-20min in the stirring process.
Preferably, the cleavage product decarboxylation has the chemical formula:
C 4 H 6 O 2 →CO 2 +C 3 H 6 (1)；
C 4 H 6 O 2 →CO+C 2 H 4 +CH 2 O (2)。
preferably, the inert solvent includes N, N-dimethylpropionamide, N-methylpyrrolidone, dimethylsulfoxide, polyethylene glycol ether, 1, 3-dimethylpropylene urea, tetrahydronaphthalene and hexamethylphosphoramide, and the concentration of the inert solvent is 15 to 30%.
Preferably, the pressure used for rectification is normal pressure, the impurities are separated by filtering out sediment in the solution by a filter, the impurities are separated and then distilled at a high temperature of 190-210 ℃, and condensate is collected to obtain the high-purity cyclopropyl methyl ketone.
The invention has the technical effects and advantages that:
the invention firstly needs to prepare the raw material alpha-acetyl-gamma-butyrolactone, thus ensuring the purity of the raw material by preparing the raw material, improving the purity of the raw material preparation by extracting and distilling in the subsequent process in the preparation process, ensuring the stable source of the raw material in the setting of the subsequent synthetic preparation, simultaneously omitting the impurity removal process in the subsequent synthetic preparation process, ensuring the more stable subsequent synthetic preparation process and ensuring the more definite and simple process.
Drawings
FIG. 1 is a schematic flow chart of the synthesis method of the present invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The invention provides a method for synthesizing cyclopropyl methyl ketone shown in figure 1, which comprises the following steps of;
s1, preparing raw materials of alpha-acetyl-gamma-butyrolactone, acylating diketene and absolute ethyl alcohol under the catalysis of a catalyst to generate ethyl acetoacetate, condensing and ring-closing the product by adding the catalyst to generate sodium acetylbutyrolactone, acidifying with hydrochloric acid, extracting with benzene, and distilling to obtain the product;
alpha-acetyl-gamma-butyrolactone is a light liquid with ester smell and boiling point of 107-108 deg.c (5 mmHg) and relative density of 1.185; it is an important raw material for synthesizing vitamin B, and is also an intermediate for synthesizing 3, 4-disubstituted-group-3' -N-ethyl-q-methyl-cellorange.
Specifically, the catalyst used for acylating the diketene and the absolute ethyl alcohol is sodium ethoxide, and the catalyst for condensing and closing the loop of the acetoacetic acid ethyl ester is ethylene oxide and sodium hydroxide.
Diketene, also known as acetyl ketene, diketene, is an organic compound of the formula C4H402, mainly used as pharmaceutical intermediates, food preservatives, pigments and regulators, which in this case act as regulators;
absolute ethanol is an aqueous ethanol solution with high purity, which is a mixture of ethanol and water, and is generally referred to as an ethanol solution with a concentration of 99.5% as absolute ethanol, which is miscible with water in any ratio, and is miscible with most organic solvents such as ether, chloroform, glycerol, etc., and is used as an organic solvent in this embodiment.
S2, hydrolyzing the alpha-acetyl-gamma-butyrolactone, putting the prepared alpha-acetyl-gamma-butyrolactone into a catalytic reactor, filling nitrogen, heating, adding a catalyst for replacement cracking, and obtaining a cracking product;
specifically, the temperature for heating the hydrolysis process of the alpha-acetyl-gamma-butyrolactone is 120-140 ℃, the moisture content standard of nitrogen is 100ppm, and the moisture content standard of high-purity nitrogen is 100 ppm=100 uL/L.
The hydrolysis catalyst of the alpha-acetyl-gamma-butyrolactone comprises the components of sodium iodide, potassium iodide, sodium bromide, potassium bromide, sodium chloride and potassium chloride;
sodium iodide is an inorganic compound, has a chemical formula of NaI, a molecular weight of 149.89, is colorless cubic crystals or white granules, is a white solid formed by reacting sodium carbonate or sodium hydroxide with hydroiodic acid and then evaporating a solution, and has the advantages of no water, dihydrate and pentahydrate, and sodium iodide is sodium iodide to ZIF-67=1.2 to 0.8;
the potassium bromide is an inorganic substance, the chemical formula is KBr, the relative molecular weight is 119.00, colorless crystals or white powder has strong salty taste, light color yellowing is seen, the potassium bromide has a little hygroscopicity, 1g of the potassium bromide is dissolved in 1.5ml of water, the water solution is neutral, the relative density is 2.75 (25 ℃), the melting point is 730 ℃, the boiling point is 1435 ℃, and the potassium bromide can be used as a catalyst to accelerate the hydrolysis of alpha-acetyl-gamma-butyrolactone.
The particle size of the catalyst is 800-1000 microns, the catalyst is stirred at a rotating speed of 200r/min in the hydrolysis catalysis process, the stirring time is 3-5h, stirring is carried out after stirring for 15-20min each time in the stirring process, the stirring is carried out for 3-5min each time, the temperature is regulated to room temperature after the reaction is finished, the system is vacuumized firstly, tail gas is removed, the tail gas is treated, then nitrogen is introduced for replacement circulation until the reaction is completed, and the vacuumizing treatment is carried out through a vacuum pump.
The cleavage product decarboxylation has the chemical reaction formula:
C 4 H 6 O 2 →CO 2 +C 3 H 6 (1)；
C 4 H 6 O 2 →CO+C 2 H 4 +CH 2 O (2)。
experiments prove that the decarbonylation of the gamma-butyrolactone is performed in a synergistic mode, the decarboxylation is performed in a stepwise mode, the total energy barrier of the decarboxylation reaction is lower than that of the decarbonylation reaction for the gamma-butyrolactone, and the alpha-acetyl-gamma-butyrolactone is formed by connecting an acetyl group on the third carbon group of the gamma-butyrolactone, so that the electron withdrawing effect of the acetyl group is more favorable for the decarboxylation reaction.
S3, decarboxylation and chlorination of a cracking product are carried out, the cracking product is added into a jacketed reactor, then the temperature is raised, a mixed solvent of N-dimethylformamide and chlorobenzene is added into the jacketed reactor, and an inert solvent is added for reaction, so that a crude cyclopropyl methyl ketone product is obtained;
specifically, the inert solvent comprises N, N-dimethylpropionamide, N-methylpyrrolidone, dimethylsulfoxide, polyethylene glycol ether, 1, 3-dimethylpropyleneurea, tetrahydronaphthalene and hexamethylphosphoramide, and the concentration of the inert solvent is 15-30%.
The inert solvent adopted in the scheme is an even aprotic solvent, the dielectric constant of the solvent is larger than 15, the dipole moment is larger than 8.34 multiplied by 10 < -30 > C.m, hydrogen in molecules is firmly combined with atoms in the molecules, protons are not easy to give out, the solvent does not have acid-base properties or extremely weak acid-base properties, and the solvent does not have proton transfer process, so that the solvent does not participate in or influence the cracking of the alpha-acetyl-gamma-butyrolactone, the boiling point of the solvent has a large difference from the boiling point of the product cyclopropyl methyl ketone, and the separation is convenient.
The general decarboxylation reaction does not require a special catalyst, but is carried out under the following conditions: the most commonly used decarboxylation method is to heat the sodium salt of the carboxylic acid with soda lime (CaO + NaOH) or solid sodium hydroxide to effect the decarboxylation reaction, i.e., substitution of-COONa with H atoms, to produce an alkane having one less carbon atom than the sodium salt of the carboxylic acid.
The reaction mechanism of decarboxylation is that carboxylate is first decarboxylated to produce carbon dioxide and methyl negative ion (-CH 3-), and methyl negative ion is one alkali with high activity and can deprive hydrogen in water to produce methane. The carboxyl in the petroleum acid is subjected to thermal cracking reaction and decarboxylation at a temperature above 300 ℃ and is converted into hydrocarbon substances, and the higher the relative molecular mass is, the higher the decomposition temperature is. It can be seen that temperature is the main factor affecting this decarboxylation reaction.
S4, carrying out distillation cyclization on the crude cyclopropyl methyl ketone, transferring the crude cyclopropyl methyl ketone into a rectifying tower, carrying out high-tower split flow at first, rectifying, and separating impurities by adjusting the reflux ratio to obtain high-purity cyclopropyl methyl ketone;
the pressure used for rectification is normal pressure, and the impurity separation is to filter out sediment in the solution by using a filter, and then the high temperature of 190-210 ℃ is used for distillation after the impurity separation, and condensate is collected to obtain the high-purity cyclopropyl methyl ketone.
In the rectification operation, the ratio of the reflux flow L returned from the top of the rectification column to the flow D of the product at the top of the column, namely R=L/D, has important influence on the separation effect and economy of the rectification process.
Finally, it should be noted that: the foregoing description is only illustrative of the preferred embodiments of the present invention, and although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described, or equivalents may be substituted for elements thereof, and any modifications, equivalents, improvements or changes may be made without departing from the spirit and principles of the present invention.
Claims (8)
1. A method for synthesizing cyclopropyl methyl ketone, which is characterized by comprising the following steps of;
s1, preparing raw materials of alpha-acetyl-gamma-butyrolactone, acylating diketene and absolute ethyl alcohol under the catalysis of a catalyst to generate ethyl acetoacetate, condensing and ring-closing the product by adding the catalyst to generate sodium acetylbutyrolactone, acidifying with hydrochloric acid, extracting with benzene, and distilling to obtain the product;
s2, hydrolyzing the alpha-acetyl-gamma-butyrolactone, putting the prepared alpha-acetyl-gamma-butyrolactone into a catalytic reactor, filling nitrogen, heating, adding a catalyst for replacement cracking, and obtaining a cracking product;
s3, decarboxylation and chlorination of a cracking product are carried out, the cracking product is added into a jacketed reactor, then the temperature is raised, a mixed solvent of N-dimethylformamide and chlorobenzene is added into the jacketed reactor, and meanwhile, an inert solvent is added for reaction, so that a crude cyclopropyl methyl ketone product is obtained;
s4, carrying out distillation cyclization on the crude cyclopropyl methyl ketone, transferring the crude cyclopropyl methyl ketone into a rectifying tower, carrying out high-tower split flow, rectifying, and separating impurities by adjusting the reflux ratio to obtain high-purity cyclopropyl methyl ketone.
2. The method for synthesizing cyclopropyl methyl ketone according to claim 1, wherein the catalyst used for acylating the diketene and the absolute ethyl alcohol is sodium ethoxide, and the catalyst for condensing and closing the ring of the acetoacetate is ethylene oxide and sodium hydroxide.
3. The method for synthesizing cyclopropylmethyl ketone according to claim 1, wherein the temperature at which the hydrolysis process of α -acetyl- γ -butyrolactone is heated is 120-140 ℃, and the moisture content of the nitrogen gas is 100ppm.
4. The method for synthesizing cyclopropylmethyl ketone according to claim 1, wherein the composition of the hydrolysis catalyst for α -acetyl- γ -butyrolactone comprises sodium iodide, potassium iodide, sodium bromide, potassium bromide, sodium chloride, and potassium chloride.
5. The method for synthesizing cyclopropylmethyl ketone according to claim 4, wherein the particle size of the catalyst is 800-1000 μm, stirring is performed at a rotation speed of 200r/min during the hydrolysis catalysis, the stirring time is 3-5h, and stirring is performed at intervals of 3-5min after each stirring time is 15-20min during the stirring.
6. The method for synthesizing cyclopropylmethyl ketone according to claim 1, wherein the decarboxylation of the cleavage product has the following chemical reaction formula:
C 4 H 6 O 2 →CO 2 +C 3 H 6 (1)；
C 4 H 6 O 2 →CO+C 2 H 4 +CH 2 O (2)。
7. the method for synthesizing cyclopropylmethyl ketone according to claim 1, wherein the inert solvent comprises N, N-dimethylpropionamide, N-methylpyrrolidone, dimethylsulfoxide, polyethylene glycol ether, 1, 3-dimethylpropyleneurea, tetrahydronaphthalene, and hexamethylphosphoramide, and the inert solvent has a concentration of 15 to 30%.
8. The method for synthesizing cyclopropyl methyl ketone according to claim 1, wherein the pressure used in the rectification is normal pressure, the impurities are separated by filtering out precipitates in the solution by a filter, the impurities are separated and distilled at a high temperature of 190-210 ℃, and condensate is collected to obtain the cyclopropyl methyl ketone with high purity.
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