CN116063183B - Synthesis method of cyclopropylamine - Google Patents
Synthesis method of cyclopropylamine Download PDFInfo
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- CN116063183B CN116063183B CN202310042415.4A CN202310042415A CN116063183B CN 116063183 B CN116063183 B CN 116063183B CN 202310042415 A CN202310042415 A CN 202310042415A CN 116063183 B CN116063183 B CN 116063183B
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- cyclopropylamine
- cyclopropylnitrile
- sodium hydroxide
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- sodium hypochlorite
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/54—Preparation of compounds containing amino groups bound to a carbon skeleton by rearrangement reactions
- C07C209/56—Preparation of compounds containing amino groups bound to a carbon skeleton by rearrangement reactions from carboxylic acids involving a Hofmann, Curtius, Schmidt, or Lossen-type rearrangement
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/54—Preparation of compounds containing amino groups bound to a carbon skeleton by rearrangement reactions
- C07C209/58—Preparation of compounds containing amino groups bound to a carbon skeleton by rearrangement reactions from or via amides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Abstract
The invention discloses a method for synthesizing cyclopropylamine, which belongs to the technical field of cyclopropylamine, and comprises the steps of adding water, cyclopropylnitrile, sodium hydroxide solution, sodium hypochlorite solution and tetrabutylammonium bromide into a reaction vessel, stirring, carrying out heat preservation reaction at 50-70 ℃, sampling and detecting every 1.5h in the reaction process, and distilling out a fraction at 48-52 ℃ under normal pressure after the cyclopropylnitrile is completely reacted to obtain cyclopropylamine; the molar ratio of the cyclopropylnitrile to the sodium hydroxide in the sodium hydroxide solution to the sodium hypochlorite in the sodium hypochlorite solution to the tetrabutylammonium bromide is 1:0.2-0.8:0.48-0.54:0.01-0.1; the invention can realize the purposes of simplified steps, material saving, high yield of target products and reduced production cost.
Description
Technical Field
The invention relates to the technical field of cyclopropylamine, in particular to a method for synthesizing cyclopropylamine.
Background
Cyclopropylamine is an important pharmaceutical intermediate and agricultural chemical intermediate, and is mainly used for producing ciprofloxacin and ciprofloxacin, and is also used for synthesizing pesticides and plant protection agents.
The existing cyclopropylamine synthesis method is that cyclopropylnitrile is hydrolyzed into cyclopropylamide under alkaline heating condition, after pure cyclopropylamide is obtained through neutralization, extraction and distillation, cyclopropylamine is obtained through Hofmann rearrangement, and the yield of cyclopropylamine after two steps of reaction is 76.4%. The post-treatment of the cyclopropylamide synthesized by the method has more steps and also needs neutralization. The Huffman rearrangement of the cyclopropylamide in the next reaction needs to be carried out under alkaline condition, so that acid is used for neutralizing alkali in the post-treatment of the cyclopropylamide, and waste of acid and alkali is caused. Furthermore, the overall yield of the two-step reaction from cyclopropylnitrile to cyclopropylamine is low.
Disclosure of Invention
Aiming at the defects existing in the prior art, the invention provides a method for synthesizing cyclopropylamine, which can achieve the purposes of simplified steps, material saving, high yield of target products and reduced production cost.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a synthetic method of cyclopropylamine comprises the following steps:
adding water, cyclopropylnitrile, sodium hydroxide solution, sodium hypochlorite solution and tetrabutylammonium bromide into a reaction vessel, stirring, performing heat preservation reaction at 50-70 ℃, sampling and detecting every 1.5h in the reaction process, and distilling out a fraction at 48-52 ℃ under normal pressure after the cyclopropylnitrile is completely reacted to obtain cyclopropylamine;
the mass fraction of sodium hydroxide in the sodium hydroxide solution is 32%;
the content of available chlorine in the sodium hypochlorite solution is 13-16%;
wherein the weight ratio of water to cyclopropylnitrile is 45:15;
wherein, the mol ratio of the cyclopropylnitrile to the sodium hydroxide in the sodium hydroxide solution to the sodium hypochlorite in the sodium hypochlorite solution to the tetrabutylammonium bromide is 1:0.2-0.8:0.48-0.54:0.01-0.1;
the stirring speed at the time of stirring was 280rpm.
Compared with the prior art, the invention has the beneficial effects that:
(1) The synthesis method of cyclopropylamine does not need to synthesize and separate cyclopropylamide, and hydrolysis and rearrangement are carried out simultaneously, so that the reaction steps and operation can be simplified;
(2) According to the synthesis method of cyclopropylamine, as no separation of cyclopropylamide is carried out, the alkali of a reaction system is not needed to be neutralized by acid, and the Huffman rearrangement is not needed to be carried out by adding the alkali again, so that materials can be saved;
(3) The method for synthesizing cyclopropylamine can improve the purity and the yield of cyclopropylamine synthesized by cyclopropylnitrile, and the gas phase purity of the prepared cyclopropylamine is 100%, and the yield is 93.7-95.1%.
Drawings
FIG. 1 is a gas chromatogram of a cyclopropylamine standard;
FIG. 2 is a gas chromatogram of cyclopropylamine prepared in example 1;
FIG. 3 is a gas chromatogram of cyclopropylamine prepared in example 2;
FIG. 4 is a gas chromatogram of cyclopropylamine prepared in example 3;
FIG. 5 is a gas chromatogram of cyclopropylamine prepared in example 4;
FIG. 6 is a gas chromatogram of cyclopropylamine prepared in example 5;
FIG. 7 is a gas chromatogram of cyclopropylamine prepared in example 6;
FIG. 8 is a gas chromatogram of cyclopropylamine prepared in example 7.
Detailed Description
Specific embodiments of the present invention will now be described in order to provide a clearer understanding of the technical features, objects and effects of the present invention.
The yields in the examples are the molar yields of cyclopropylamine synthesized from cyclopropylnitrile.
Example 1
45g of water, 15g of cyclopropylnitrile, 14.0g (0.5 times of the molar quantity of the cyclopropylnitrile) of 32% sodium hydroxide solution, 55.5g (0.51 times of the molar quantity of the cyclopropylnitrile) of sodium hypochlorite solution and 3.6g (0.05 times of the molar quantity of the cyclopropylnitrile) of tetrabutylammonium bromide are added into a reaction vessel, stirring is started, the stirring speed is controlled to 280rpm, the reaction is carried out at 60 ℃, every 1.5h of sampling gas phase detection is carried out in the reaction process, after the cyclopropylnitrile is completely reacted through the detection result, the fraction at 48-52 ℃ is distilled out at normal pressure, the fraction quality is 12.05g, the gas phase chromatographic analysis is carried out on the fraction, the gas phase purity of the cyclopropylamine in the fraction is 100%, and the molar yield of the cyclopropylamine is 94.4% as shown in the gas phase chromatographic chart shown in figure 2;
the manufacturer of the sodium hypochlorite solution is Shanghai Micin Biochemical technology Co., ltd, and the content of available chlorine is 13-16%.
Example 2
45g of water, 15g of cyclopropylnitrile, 5.6g (0.2 times the molar amount of cyclopropylnitrile) of 32% sodium hydroxide solution, 55.5g (0.51 times the molar amount of cyclopropylnitrile) of sodium hypochlorite solution, 3.6g (0.05 times the molar amount of cyclopropylnitrile) of tetrabutylammonium bromide are charged into a reaction vessel; stirring is started, the stirring speed is controlled to 280rpm, the thermal insulation reaction is carried out at 60 ℃, gas phase detection is carried out every 1.5h in the reaction process, the fraction at 48-52 ℃ is distilled out under normal pressure after the cyclopropanecarbonitrile is completely reacted according to the detection result, the fraction quality is 12.00g, the gas chromatographic analysis is carried out on the fraction, the gas chromatographic chart is shown in figure 3, the gas phase purity of cyclopropylamine in the fraction is 100%, and the molar yield of cyclopropylamine is 94.0%;
the manufacturer of the sodium hypochlorite solution is Shanghai Micin Biochemical technology Co., ltd, and the content of available chlorine is 13-16%.
Example 3
45g of water, 15g of cyclopropylnitrile, 22.4g (0.8 times the molar amount of cyclopropylnitrile) of 32% sodium hydroxide solution, 55.5g (0.51 times the molar amount of cyclopropylnitrile) of sodium hypochlorite solution, 3.6g (0.05 times the molar amount of cyclopropylnitrile) of tetrabutylammonium bromide are charged into a reaction vessel; stirring is started, the stirring speed is controlled to 280rpm, the thermal insulation reaction is carried out at 60 ℃, gas phase detection is carried out every 1.5h in the reaction process, the fraction at 48-52 ℃ is distilled out under normal pressure after the cyclopropanecarbonitrile is completely reacted according to the detection result, the fraction quality is 12.12g, the gas chromatographic analysis is carried out on the fraction, the gas chromatographic chart is shown in figure 4, the gas phase purity of cyclopropylamine in the fraction is 100%, and the molar yield of cyclopropylamine is 94.9%;
the manufacturer of the sodium hypochlorite solution is Shanghai Micin Biochemical technology Co., ltd, and the content of available chlorine is 13-16%.
Example 4
45g of water, 15g of cyclopropylnitrile, 14.0g (0.5 times the molar amount of cyclopropylnitrile) of 32% sodium hydroxide solution, 41.6g (0.48 times the molar amount of cyclopropylnitrile) of sodium hypochlorite solution, 3.6g (0.05 times the molar amount of cyclopropylnitrile) of tetrabutylammonium bromide are charged into a reaction vessel; stirring is started, the stirring speed is controlled to 280rpm, the thermal insulation reaction is carried out at 60 ℃, gas phase detection is carried out every 1.5h in the reaction process, the fraction at 48-52 ℃ is distilled out under normal pressure after the cyclopropanecarbonitrile is completely reacted according to the detection result, the fraction quality is 12.03g, the gas chromatographic analysis is carried out on the fraction, the gas chromatographic chart is shown in figure 5, the gas phase purity of cyclopropylamine in the fraction is 100%, and the molar yield of cyclopropylamine is 94.2%;
the manufacturer of the sodium hypochlorite solution is Shanghai Micin Biochemical technology Co., ltd, and the content of available chlorine is 13-16%.
Example 5
45g of water, 15g of cyclopropylnitrile, 14.0g (0.5 times the molar amount of cyclopropylnitrile) of 32% sodium hydroxide solution, 69.4g (0.54 times the molar amount of cyclopropylnitrile) of sodium hypochlorite solution, 3.60g (0.05 times the molar amount of cyclopropylnitrile) of tetrabutylammonium bromide are charged into a reaction vessel; stirring is started, the stirring speed is controlled to 280rpm, the thermal insulation reaction is carried out at 60 ℃, gas phase detection is carried out every 1.5h in the reaction process, the fraction at 48-52 ℃ is distilled out under normal pressure after the cyclopropanecarbonitrile is completely reacted according to the detection result, the fraction quality is 12.14g, the gas chromatographic analysis is carried out on the fraction, the gas chromatographic chart is shown in figure 6, the gas phase purity of cyclopropylamine in the fraction is 100%, and the mol yield of cyclopropylamine is 95.1%;
the manufacturer of the sodium hypochlorite solution is Shanghai Micin Biochemical technology Co., ltd, and the content of available chlorine is 13-16%.
Example 6
45g of water, 15g of cyclopropylnitrile, 14.0g (0.5 times the molar amount of cyclopropylnitrile) of 32% sodium hydroxide solution, 55.5g (0.51 times the molar amount of cyclopropylnitrile) of sodium hypochlorite solution, 0.72g (0.01 times the molar amount of cyclopropylnitrile) of tetrabutylammonium bromide are charged into a reaction vessel; stirring is started, the stirring speed is controlled to 280rpm, the reaction is carried out at 50 ℃, gas phase detection is carried out every 1.5h in the reaction process, the fraction at 48-52 ℃ is distilled out under normal pressure after the cyclopropanenitrile is completely reacted according to the detection result, the fraction quality is 11.96g, the gas chromatographic analysis is carried out on the fraction, the gas chromatographic chart is shown in figure 7, the gas phase purity of cyclopropylamine in the fraction is 100%, and the molar yield of cyclopropylamine is 93.7%;
the manufacturer of the sodium hypochlorite solution is Shanghai Micin Biochemical technology Co., ltd, and the content of available chlorine is 13-16%.
Example 7
45g of water, 15g of cyclopropylnitrile, 14.0g (0.5 times the molar amount of cyclopropylnitrile) of 32% sodium hydroxide solution, 55.5g (0.51 times the molar amount of cyclopropylnitrile) of sodium hypochlorite solution, 7.21g (0.1 times the molar amount of cyclopropylnitrile) of tetrabutylammonium bromide are charged into a reaction vessel; stirring is started, the stirring speed is controlled to 280rpm, the thermal insulation reaction is carried out at 70 ℃, gas phase detection is carried out every 1.5h in the reaction process, the fraction at 48-52 ℃ is distilled out under normal pressure after the cyclopropanecarbonitrile is completely reacted according to the detection result, the fraction quality is 12.08g, the gas chromatographic analysis is carried out on the fraction, the gas chromatographic chart is shown in figure 8, the gas phase purity of cyclopropylamine in the fraction is 100%, and the molar yield of cyclopropylamine is 94.6%;
the manufacturer of the sodium hypochlorite solution is Shanghai Micin Biochemical technology Co., ltd, and the content of available chlorine is 13-16%.
The gas chromatography analysis is carried out on the cyclopropylamine standard, the gas chromatography is shown in figure 1, and the peaks are consistent after the analysis is carried out on the gas chromatography of the cyclopropylamine standard and the fractions obtained in examples 1-7, so that the fractions obtained in examples 1-7 are proved to be cyclopropylamine.
The percentages used in the present invention are mass percentages unless otherwise indicated.
Finally, it should be noted that: the foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited thereto, but it is to be understood that modifications and equivalents of some of the technical features described in the foregoing embodiments may be made by those skilled in the art, although the present invention has been described in detail with reference to the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (2)
1. The synthesis process of cyclopropylamine includes adding water, cyclopropylnitrile, sodium hydroxide solution, sodium hypochlorite solution and tetrabutylammonium bromide into a reaction container, stirring, heat insulating reaction at 50-70 deg.c for every 1.5 hr, sampling and detecting to obtain cyclopropylamine after the cyclopropylnitrile has reacted completely, and distilling out fraction at 48-52 deg.c;
the molar ratio of the cyclopropylnitrile to the sodium hydroxide in the sodium hydroxide solution to the sodium hypochlorite in the sodium hypochlorite solution to the tetrabutylammonium bromide is 1:0.2-0.8:0.48-0.54:0.01-0.1;
the weight ratio of water to cyclopropylnitrile is 3:1;
the mass fraction of sodium hydroxide in the sodium hydroxide solution is 32%;
the content of available chlorine in the sodium hypochlorite solution is 13-16%.
2. The method for synthesizing cyclopropylamine according to claim 1, wherein the stirring speed at the time of stirring is 280rpm.
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| US20080319204A1 (en) * | 2007-06-25 | 2008-12-25 | Wyeth | Process for the synthesis of progesterone receptor modulators |
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| JP2013507391A (en) * | 2009-10-09 | 2013-03-04 | アカオジェン インコーポレイテッド | Antiviral aminoglycoside analogues |
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