CN112479854A

CN112479854A - Green process for producing cyclopropyl formic acid

Info

Publication number: CN112479854A
Application number: CN202011422697.3A
Authority: CN
Inventors: 胡志辉; 李明霞
Original assignee: Suzhou Yangke New Material Technology Co ltd
Current assignee: Hangzhou Longjing Pharmaceutical Technology Co ltd
Priority date: 2020-12-08
Filing date: 2020-12-08
Publication date: 2021-03-12
Anticipated expiration: 2040-12-08
Also published as: CN112479854B

Abstract

The invention relates to a green process for producing cyclopropyl formic acid, which takes methyl cyclopropanecarboxylate as a raw material, and obtains the cyclopropyl formic acid by one-step hydrolysis under the catalysis of dilute sulfuric acid, and simultaneously generates a methanol byproduct; the process adopts a mode of recovering methanol while hydrolyzing and rectifying, after the hydrolysis reaction is finished, a lower layer dilute sulfuric acid aqueous solution is separated, the dilute sulfuric acid aqueous solution can be repeatedly used, no waste liquid is generated, and after the layering is finished, the temperature is directly raised and the reduced pressure rectification is carried out to obtain the product. The invention can complete production by only one rectifying device through a one-step hydrolysis method, has simple process, less occupied equipment, high productivity and environment-friendly process; the purity of the target product, namely the cyclopropyl formic acid, reaches 99.5 percent, the moisture content is less than 0.1 percent, the yield reaches 98 percent, and the dilute sulfuric acid required by hydrolysis can be repeatedly used without generating three wastes; the purity of the by-product methanol can reach 99.9%, the water content is less than 0.1%, and the by-product methanol can be recycled.

Description

Green process for producing cyclopropyl formic acid

Technical Field

The invention belongs to the field of organic matter production processes, and particularly relates to a green process for producing cyclopropyl formic acid.

Background

The cyclopropyl formic acid is an intermediate widely used in the pharmaceutical and pesticide industries, can be used for synthesizing high-efficiency antibacterial new medicines such as ciprofloxacin, ciprofloxacin and ciprofloxacin, and also can be widely used for synthesizing other fine chemical products; therefore, a reasonable synthetic route is developed, and the method has great social benefit and economic benefit. The literature reports that the common synthesis methods of the cyclopropyl formic acid are as follows:

(1) the compound is prepared by taking 1-chloro-3-bromopropane as a raw material and performing cyanidation, cyclization and hydrolysis;

(2) 1, 3-propylene glycol is used as a raw material, and is firstly mixed with thionyl chloride to generate cyclic sulfite, and then the cyclic sulfite is oxidized into cyclic sulfate; is obtained by cyclization, cyanidation and hydrolysis;

(3) the compound is prepared by using 1, 3-propylene glycol as a raw material through bromination, cyanidation, cyclocondensation and hydrolysis;

(4) taking diethyl malonate and 1, 2-dibromoethane as raw materials, generating cyclopropyl dicarboxylic ester through cyclocondensation, and hydrolyzing, heating and decarboxylating to obtain the compound;

(5) generating substituted gamma butyrolactone by using ethyl acetoacetate as a raw material and ethylene oxide, and then performing chlorination, cyclic condensation and oxidation to obtain the gamma butyrolactone;

(6) and the gamma-butyrolactone is used as a raw material to generate chlorobutyrate with thionyl chloride, and the chlorobutyrate is cyclized to obtain the compound.

The method generally has the defects of expensive raw materials, harsh reaction conditions, strict requirements on equipment and control conditions, low total yield, low practical value, large amount of three wastes and the like.

Disclosure of Invention

Aiming at the defects in the prior art, the invention aims to simplify the preparation process of the cyclopropyl formic acid, provide a green production method, and can not generate a large amount of wastewater in the production process, and the generated by-products can be recycled.

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

a green process for producing cyclopropyl formic acid comprises the following steps,

s1: adding cyclopropyl formate and concentrated sulfuric acid into a reaction kettle, heating to raise the temperature, and then slowly dropwise adding water into the reaction kettle;

s2: keeping the temperature at 60-110 ℃, and collecting by-products by using a rectifying column;

s3: after the water is dripped, the temperature is reduced to 60-80 ℃ for continuous reaction;

s4: detecting the content of the cyclopropyl formate by using GC, stopping the reaction when the content of the cyclopropyl formate is lower than 1%, and naturally cooling;

s5: naturally cooling to room temperature, pouring the reaction liquid in the reaction kettle into a separating funnel, collecting an organic layer and an acid water layer, and continuously carrying out vacuum rectification on the organic layer to obtain the cyclopropyl formic acid.

Further, the cyclopropyl formic acid ester: water: the mass ratio of concentrated sulfuric acid is 1: 0.25-0.5: 0.1 to 0.4.

Further, heating to 80-100 ℃ in the S1.

Further, the cyclopropyl formic acid ester is selected from one of methyl cyclopropyl formate, ethyl cyclopropyl formate, n-butyl cyclopropyl formate, propyl cyclopropyl formate or isopropyl cyclopropyl formate, and more preferably methyl cyclopropyl formate.

Further, in the step S3, the water is controlled to be dripped within 4-8 hours, and the reaction is continued for 2-3 hours after the water is dripped.

The invention has the beneficial effects that: the invention can complete production by only one rectifying device through a one-step hydrolysis method, has simple process, less occupied equipment, high productivity and environment-friendly process; the purity of the target product, namely the cyclopropyl formic acid, is close to 100 percent, the moisture content is less than 0.1 percent, the yield reaches 98 percent, and the economic benefit is high; the dilute sulfuric acid required by hydrolysis can be repeatedly used, no three wastes are generated, and the method is green and environment-friendly; the purity of the byproduct methanol generated in the production can also reach 99.9 percent, the moisture content is less than 0.1 percent, the product meets the market specification, and the product can be used as other production raw materials.

Drawings

Fig. 1 is a flow chart of a process for producing cyclopropylcarboxylic acid according to an embodiment of the present invention.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

In addition, the technical features involved in the different embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.

Example (b): as shown in fig. 1, the present invention provides a green process for producing cyclopropylcarboxylic acid:

firstly, putting 3000kg of methyl cyclopropyl formate and 40kg of concentrated sulfuric acid into an enamel reaction kettle with a rectifying tower, heating to 95-100 ℃, and then slowly dropwise adding 1080kg of water into the reaction kettle;

controlling the water to be dripped within 6-7h, and keeping the temperature at 110 ℃ after the water is dripped, and simultaneously collecting the methanol by using a rectification column;

the temperature is reduced to 60-80 ℃ to continue the reaction for 2-3h, and the reaction is stopped;

the water separation layer of the reaction is transferred to an acid water transfer barrel to be directly applied to the next batch of production, and the organic layer is continuously rectified under reduced pressure to obtain 2530kg of cyclopropyl formic acid, wherein the yield reaches 98.1 percent, and the gas phase purity reaches 99.5 percent.

In the embodiment, methyl cyclopropanecarboxylate is taken as a raw material, methyl cyclopropanecarboxylate is hydrolyzed in one step under the catalysis of dilute sulfuric acid to obtain the cyclopropyl formic acid, and a methanol byproduct is generated at the same time, the methanol is recovered by adopting a mode of hydrolysis and rectification, after the hydrolysis reaction is finished, a reaction solution is layered to obtain an organic layer and a dilute sulfuric acid aqueous solution, and the dilute sulfuric acid aqueous solution can be repeatedly used without generating waste liquid; the organic layer is directly heated and decompressed and rectified to obtain the product, the purity of the finally obtained cyclopropyl formic acid is close to 100%, the yield can reach more than 98%, and the whole production flow is simple in process, economical and environment-friendly.

While embodiments of the invention have been described above, it is not limited to the applications set forth in the description and the embodiments, which are fully applicable in various fields of endeavor to which the invention pertains, and further modifications may readily be made by those skilled in the art, it being understood that the invention is not limited to the details shown and described herein without departing from the general concept defined by the appended claims and their equivalents.

Claims

1. A green process for producing cyclopropyl formic acid is characterized by comprising the following steps:

2. A green process for the production of cyclopropylcarboxylic acid according to claim 1, wherein the cyclopropanecarboxylate: water: the mass ratio of concentrated sulfuric acid is 1: 0.25-0.5: 0.1 to 0.4.

3. A green process for preparing cyclopropylcarboxylic acid according to claim 1, where in S1 the temperature is raised to 80-100 ℃.

4. The green process for producing cyclopropylcarboxylic acid of claim 1, wherein the cyclopropylcarboxylic acid ester is selected from the group consisting of methyl cyclopropylformate, ethyl cyclopropylformate, n-butyl cyclopropylformate, propyl cyclopropylformate and isopropyl cyclopropylformate.

5. A green process for the production of cyclopropylcarboxylic acid of claim 4, where the cyclopropylcarboxylic acid is methyl cyclopropylcarboxylate.

6. The green process for preparing cyclopropylformic acid of claim 1, wherein in S3, the water is controlled to be added in 4-8h, and the reaction is continued for 2-3h after the water is added.