Preparation Method and Application of 3-Methyl-3-amino-1-pentyne

Abstract

The present invention provides a preparation method of 3-methyl-3-amino-1-pentyne. First, in the presence of sulfuric acid, hydrochloric acid and a catalyst, or in the presence of sulfuric acid, hydrochloric acid and by introducing hydrogen chloride gas and a catalyst, 3-methyl-1-pentyn-3-ol undergoes an alkyne chlorination reaction, and 3-methyl-3-chloro-1-pentyne is obtained by separation; then, in the presence of ammonia water and by introducing ammonia gas and a catalyst, 3-methyl-3-chloro-1-pentyne undergoes an ammoniation reaction, and 3-methyl-3-amino-1-pentyne is obtained by separation. The preparation method of the present invention is more convenient to implement in the process, has a high yield, and has the prospect of industrial application. The content of the product obtained by the method of the present invention is ≥95%, and there is no need for purification, or only conventional vacuum distillation is required to meet the synthesis process of zoxamide. In addition, the product of the present invention is obtained by the static separation method, and the acid layer and ammonia water layer obtained in the static separation operation can be recycled or applied to the upstream process, which has environmental protection and economic significance.

Description

Technical Field

[0001] The present invention relates to a method for preparing 3-methyl-3-amino-1-pentyne.

Technical Background

[0002] Zoxamide, test code RH-7281, common English name zoxamide, is a benzamide protective fungicide developed by Rohm and Haas Company (now Dow AgroSciences). It has a novel mechanism of action. It can effectively control diseases caused by oomycete fungi on crops such as fruit trees and vegetables including grapes and potatoes, such as potato and tomato late blight, cucumber downy mildew and grape downy mildew, etc. It has a special effect on grape downy mildew, and the compound patent protection has expired.

[0003] US Patent US005304572A discloses a synthetic process route of zoxamide. Among them, 3-methyl-3-amino-1-pentyne is an important key intermediate for preparing zoxamide. Chinese Invention Patent CN1183074C discloses an improved method for preparing 3-methyl-3-amino-1-pentyne. The alkynol raw material undergoes an alkynyl chlorination reaction in the presence of calcium chloride, a copper catalyst and concentrated hydrochloric acid to obtain alkynyl chloride, and the alkynyl chloride undergoes an ammoniation reaction in the presence of concentrated ammonia water and concentrated alkali to obtain 3-methyl-3-amino-1-pentyne. However, the disadvantages of this improved method are that the content and yield of alkynyl chloride are low, the yield of alkynylamine is low, and hydrolysis by-products are easily generated. It also needs to be purified by solvent extraction and rectification, and the operation is cumbersome.

[0004] Chinese Invention Patent CN101613287B also discloses a method for synthesizing 3-methyl-3-amino-1-pentyne. Through the alkynyl chlorination reaction in the presence of saturated hydrochloric acid, hydrogen chloride gas is introduced and a copper salt catalyst, alkynyl chloride undergoes an ammoniation reaction in the presence of concentrated ammonia water and concentrated alkali to obtain 3-methyl-3-amino-1-pentyne. The main reaction route is as follows:

[0005]

[0006] Side reactions:

[0007]

[0008] This method improves the yield and content, but the disadvantages are that the alkynyl chlorination reaction requires a large amount of saturated hydrochloric acid and hydrogen chloride gas, and it is not easy to layer after the reaction is completed. The ammoniation reaction using concentrated alkali is prone to hydrolysis side reactions, the yield is low, and rectification purification is still required.

Summary of the Invention

[0009] The object of the present invention is to overcome the defects of the prior art and provide a method for preparing 3-methyl-3-amino-1-pentyne with high content and high yield, reducing the occurrence of side reactions, and the obtained product 3-methyl-3-amino-1-pentyne can be directly applied to the synthesis of the fungicide zoxamide without purification or conventional distillation.

[0010] The idea of the present invention is to use 3-methyl-1-pentyn-3-ol, hydrochloric acid, and sulfuric acid as raw materials, and carry out the reaction at a suitable reaction temperature at a relatively fast speed in the presence of a catalyst, so as to complete the alkynyl chlorination reaction with a relatively high yield. The alkynyl chloride can be obtained only by liquid separation without purification and can directly enter the ammoniation reaction. Then, ammonia gas is introduced into concentrated ammonia water in the presence of a catalyst. Since strong base is not used in the reaction process, the alkynyl amination reaction is completed with a relatively high yield by selecting a suitable reaction temperature, and then the alkynyl amine is obtained by liquid separation. The obtained product can be used directly without further treatment, or 3-methyl-3-amino-1-pentyne can be obtained only by conventional vacuum distillation and applied to the synthesis of zoxamide.

[0011] Based on the above idea, the present invention provides a method for preparing 3-methyl-3-amino-1-pentyne, and the steps of the method are as follows:

[0012] (1) In the presence of sulfuric acid, hydrochloric acid and a catalyst, or in the presence of sulfuric acid, hydrochloric acid and hydrogen chloride gas introduced and a catalyst, the compound of formula (I) 3-methyl-1-pentyn-3-ol undergoes an alkynyl chlorination reaction, and the compound of formula (II) 3-methyl-3-chloro-1-pentyne is obtained by separation; the reaction formula is as follows:

[0013]

[0014] (2) Then, in the presence of ammonia water with ammonia gas introduced and a catalyst, the compound of formula (II) 3-methyl-3-chloro-1-pentyne obtained in step (1) undergoes an ammoniation reaction, and the compound of formula (III) 3-methyl-3-amino-1-pentyne is obtained by separation; the reaction formula is as follows:

[0015]

[0016] In the present invention, since the alkynyl chlorination reaction in step (1) is an exothermic reaction, in order to facilitate the reaction and temperature control, the raw material 3-methyl-1-pentyn-3-ol is generally added dropwise.

[0017] Preferably, the hydrochlorination reaction in step (1) is carried out at a temperature of -20°C to 20°C, more preferably -5°C to 5°C. A lower reaction temperature is beneficial to the progress of the reaction. When the reaction temperature is higher, the impurities generated in the reaction system will increase, affecting the reaction yield. However, maintaining a lower temperature usually increases the energy consumption of the preparation method of the present invention. Therefore, those skilled in the art can appropriately adjust the temperature on the premise of ensuring the favorable progress of the reaction. The hydrochlorination reaction time is generally 2 - 10 hours. If the time is too long, impurities are easily generated; if the time is too short, some raw materials will not react completely. It is preferably 2 - 5 hours.

[0018] According to a preferred embodiment, the hydrochloric acid in step (1) uses industrial hydrochloric acid with a mass concentration of 10 - 40%, more preferably 20 - 35%, and its molar amount is 1.0 - 2.0 times that of the raw material 3-methyl-1-pentyn-3-ol. The sulfuric acid is selected with a mass concentration of 50 - 100%, more preferably 80 - 100%, and the molar amount is also 1.0 - 2.0 times that of 3-methyl-1-pentyn-3-ol, more preferably 1.0 - 1.5 times. Using hydrochloric acid and sulfuric acid simultaneously in the system is beneficial to improving the yield of 3-methyl-3-chloro-1-pentyne.

[0019] In the present invention, in step (1), in the presence of sulfuric acid, hydrochloric acid and a catalyst, hydrogen chloride gas can be introduced into the reaction system to further increase the concentration of hydrochloric acid. The hydrogen chloride gas can use commercially available hydrogen chloride in steel cylinders, or hydrogen chloride gas generated by mixing sodium chloride and concentrated sulfuric acid, or hydrogen chloride gas obtained by mixing concentrated hydrochloric acid and concentrated sulfuric acid. The amount of hydrogen chloride gas introduced is usually 1.0 - 2.0 times the molar amount of 3-methyl-1-pentyn-3-ol. A larger amount of hydrogen chloride gas is beneficial to the reaction and shortens the reaction time, but excessive hydrogen chloride will overflow from the reaction system, increasing the burden of tail gas absorption and being unfavorable to environmental protection.

[0020] As a variant, step (1) can also be carried out by introducing hydrogen chloride gas in the presence of sulfuric acid and a catalyst, as long as the sulfuric acid and the generated hydrochloric acid in the reaction system reach an appropriate concentration.

[0021] The catalyst in step (1) is used to shorten the reaction time and can be selected from one or a mixture of copper salts, cuprous salts, silver salts, zinc salts, aluminum salts, especially copper sulfate, cuprous chloride, silver nitrate, zinc chloride, aluminum trichloride and their mixtures, and the dosage is 1 - 10% by weight of the raw material 3-methyl-1-pentyn-3-ol, more preferably 1 - 5%.

[0022] After the hydrochlorination reaction in step (1) is completed, the reaction system is separated into a lower acid layer and an upper oil layer by standing and layering. The upper oil layer is washed with water to obtain 3-methyl-3-chloro-1-pentyne. The content measured by GC is ≥95%, and the yield is ≥91%. Therefore, it can be directly used in the aminochlorination reaction without purification treatment.

[0023] The acid layer separated in step (1) is usually treated as three wastes. From the perspectives of environmental protection and economy, it can also be applied to the acetylene chlorination process. When the separated acid layer is recycled back to the acetylene chlorination process, since the hydrochloric acid in the acid layer is consumed and the concentration may be lower than that required for the reaction, it is necessary to supplement the introduction of hydrogen chloride gas and some ineffective or lost catalysts to make the acid concentration and catalyst content meet the standards, ensuring the yield and quality of the product.

[0024] After the reaction in step (1) is completed, the acid layer obtained by standing and separating can be recycled multiple times. Since the acid layer contains sulfuric acid and hydrochloric acid, when the acid layer is recycled, hydrogen chloride gas and some ineffective or lost catalysts should be appropriately supplemented according to the hydrochloric acid concentration in the acid layer to ensure that their respective concentrations in the system meet the standards.

[0025] In the present invention, the 3-methyl-3-chloro-1-pentyne obtained in step (1) is directly subjected to an ammoniation reaction. In the presence of ammonia water, ammonia gas and a catalyst, the compound of formula (II), 3-methyl-3-chloro-1-pentyne, undergoes an ammoniation reaction, and after separation, the compound of formula (III), 3-methyl-3-amino-1-pentyne, is obtained; the reaction formula is as follows:

[0026]

[0027] Preferably, the ammonia water is concentrated ammonia water with a mass concentration of 20 - 50%, or ammonia gas is introduced into dilute ammonia water at low temperature for absorption to form concentrated ammonia water until saturation and then applied to this step. A lower concentration of ammonia water will lead to a slower reaction rate and an increase in impurity content, while a too high concentration will cause excessive ammonia to overflow from the reaction system, increasing the burden of tail gas absorption.

[0028] In step (2), since 2 moles of ammonia are consumed for 1 mole of raw material in the ammoniation reaction and ammonium chloride is generated while forming the product, the ammonia concentration in the system decreases at this time. Therefore, ammonia gas should be introduced in a timely manner to maintain the ammonia concentration in the system within an appropriate range. The ammonia gas can be ammonia gas from a liquid ammonia cylinder, or the ammonia water obtained by separating the reaction system into layers can be heated and distilled to overflow ammonia gas and recycled back to the reaction system. In this step, in order to avoid generating more hydrolysis products, the process of dropping concentrated alkali is not adopted during the reaction. When recovering ammonia, liquid alkali can also be dropped to convert the reaction product ammonium chloride into ammonia, improving the utilization rate of ammonia, simultaneously solving the problem of ammonia recovery, avoiding the generation of more waste ammonia water, so as to improve economic benefits and have environmental protection significance.

[0029] In step (2), the molar amount of ammonia water is 2 - 10 times, preferably 5 - 10 times, the molar amount of 3 - methyl - 3 - chloro - 1 - pentyne. Increasing the dosage of ammonia water is beneficial to the progress of the reaction but will increase the recovery cost. The feeding amount of ammonia gas during the reaction is generally 1 - 5 times, preferably 2 - 3 times, the molar amount of 3 - methyl - 3 - chloro - 1 - pentyne. When it is excessive by too much, ammonia will overflow from the reaction system, increasing the burden of tail gas absorption.

[0030] Since step (2) is an exothermic reaction, 3 - methyl - 3 - chloro - 1 - pentyne from step (1) is usually added dropwise to the reaction system, and the system temperature can be controlled.

[0031] In this step, the ammoniation reaction catalyst is beneficial to shortening the reaction time. One or a mixture of copper salts, cuprous salts, silver salts, zinc salts, and aluminum salts can be selected. Preferably, a mixture of one or more of copper sulfate, cuprous chloride, silver nitrate, zinc chloride, and aluminum trichloride is selected. The dosage of the catalyst is 1 - 10%, more preferably 1 - 5%, based on the weight of 3 - methyl - 3 - chloro - 1 - pentyne.

[0032] Since the crude product obtained after the acetylenic chlorination reaction in step (1) is separated by a liquid - liquid separation operation, most of the catalyst used in step (1) is transferred to the aqueous layer during the liquid - liquid separation operation, and only a small amount of the catalyst remains in the crude product. Therefore, when performing the ammoniation reaction in step (2), it is usually necessary to re - add the same catalyst or add a new different catalyst for the reaction.

[0033] Similarly, after the ammoniation reaction in step (2) ends, the ammonia water layer and the upper oil - layer product are obtained by standing and liquid - liquid separation. After heating to room temperature, the residual ammonia gas is distilled off to obtain 3 - methyl - 3 - amino - 1 - pentyne product. By GC detection, it is confirmed that the product content ≥95% and the yield ≥91%. It can be directly applied to the synthesis of zoxamide, or the required 3 - methyl - 3 - amino - 1 - pentyne with GC content ≥95% and yield ≥91% is obtained by conventional vacuum distillation, which can be directly applied to the synthesis process of zoxamide, and is more beneficial to improving the content and yield of the technical drug.

[0034] The ammonia water layer obtained by standing and liquid - liquid separation contains a large amount of ammonia and ammonium chloride. The ammonia in the ammonia water layer can be recovered for reuse. During the recovery, concentrated alkali is dropped into the ammonia water layer to convert the ammonium chloride inorganic salt in the ammonia water layer into ammonia and sodium chloride to ensure complete ammonia recovery. This ammonia water layer also contains the catalyst and a large amount of ammonia, and can also be directly recycled in the process. However, since this ammonia water layer will contain a certain concentration of ammonium chloride, with the increase in the number of recycling times, the cumulative concentration of ammonium chloride will gradually increase. Therefore, the recycling is generally limited to 2 - 5 times without affecting the normal progress of the reaction of the present invention. This kind of recycling can reduce the ammonia recovery cost and save the catalyst.

[0035] Compared with the prior art, the preparation method of the present invention is more convenient in process implementation, has a high yield, and has the prospect of industrial application. The content of the product 3-methyl-3-chloro-1-pentyne obtained by the method of the present invention is ≥95%, and it does not need to be purified, or only conventional vacuum distillation is required to meet the synthesis process of zoxamide. In addition, the product of the present invention is obtained by the static separation method. In the static separation operation, the acid layer containing acid and the ammonia water layer containing ammonia can both be recycled or applied to the upstream process, which has environmental and economic significance.

Description of the Drawings

[0036] Figure 1 It is the mass spectrometry detection result of the product of Example 8;

[0037] Figure 2 It is the nuclear magnetic detection result of the product of Example 8.

Detailed Embodiments

[0038] The following examples are used to explain the technical solutions of the present invention non-limitingly.

[0039] Example 1 Preparation of 3-methyl-3-chloro-1-pentyne

[0040] Put 90 g of 30% industrial hydrochloric acid (0.74 mol) into the reaction flask, start stirring, cool it to -5 °C with a cold bath, add 3 g of copper chloride as a catalyst, control the temperature at -5 °C to 5 °C, and at the same time drop 60 g (0.60 mol) of 3-methyl-1-pentyn-3-ol raw material and 80 g (0.80 mol) of 98% concentrated sulfuric acid into the solution within 2 hours, and then keep it warm at -5 °C to 5 °C for 2 hours.

[0041] After the reaction system is allowed to stand and separate into layers, 73 g of the upper oil layer and 160 g of the lower acid layer are obtained. The oil layer is washed with 20 g of water to obtain 70 g of the product, namely 3-methyl-3-chloro-1-pentyne.

[0042] The content of the obtained product was confirmed by GC to be 97% (area normalization method), and the yield was calculated to be 95.3%.

[0043] Example 2 Preparation of 3-methyl-3-chloro-1-pentyne

[0044] The same operation as in Example 1 was carried out, except that copper sulfate was used instead of copper chloride as the catalyst, and other conditions and process operations remained unchanged. As a result, 68 g of the product 3-methyl-3-chloro-1-pentyne was obtained.

[0045] GC detection confirmed that the product content was 97%, and the calculated yield was 92.6%.

[0046] Example 3 Preparation of 3-methyl-3-chloro-1-pentyne

[0047] The procedure was the same as in Example 1, except that cuprous chloride was replaced with silver nitrate as the catalyst, and other conditions and process operations remained unchanged. 67 g of 3-methyl-3-chloro-1-pentyne was obtained.

[0048] GC detection confirmed that the product content was 97%, and the calculated yield was 91.2%.

[0049] Example 4 Preparation of 3-methyl-3-chloro-1-pentyne

[0050] The procedure was the same as in Example 1, except that the temperature was controlled at -10°C to -5°C, and other conditions and process operations remained unchanged. As a result, 70 g of 3-methyl-3-chloro-1-pentyne was obtained.

[0051] GC detection confirmed that the product content was 98%, and the calculated yield was 96.3%.

[0052] Example 5 Preparation of 3-methyl-3-chloro-1-pentyne by recycling the acid layer

[0053] 160 g of the acid layer obtained in Example 1 was charged into the reaction flask, stirring was started, and it was cooled to about -5°C in a cold bath. While controlling the temperature at -5°C to 5°C, 60 g (0.60 mol) of 3-methyl-1-pentyn-3-ol raw material and 30 g (0.82 mol) of hydrogen chloride gas were dropped into the solution within 2 hours, and then it was kept warm at -5 to 5°C for 2 hours.

[0054] After standing and separating, 73 g of the upper oil layer and 175 g of the lower acid layer were obtained. The oil layer was washed with 20 g of water to obtain 69 g of 3-methyl-3-chloro-1-pentyne.

[0055] GC detection confirmed that the product content was 97% (area normalization), and the calculated yield was 94.0%.

[0056] Example 6 Preparation of 3-methyl-3-chloro-1-pentyne by recycling the acid layer

[0057] 160 g of the acid layer obtained in Example 1 was charged into the reaction flask, stirring was started, and it was cooled to -5°C. 0.5 g of the catalyst was added, and while controlling the temperature at -5°C to 5°C, 60 g (0.60 mol) of 3-methyl-1-pentyn-3-ol raw material and 30 g (0.82 mol) of hydrogen chloride gas were dropped into the solution within 2 hours. After completion, it was kept warm at -5°C to 5°C for 2 hours.

[0058] After standing and separating, 73 g of the upper oil layer and 175 g of the lower acid layer were obtained. The oil layer was washed with 20 g of water to obtain 70 g of 3-methyl-3-chloro-1-pentyne.

[0059] GC detection confirmed that the product content was 97% (area normalization), and the calculated yield was 95.3%.

[0060] Example 7 Preparation of 3-methyl-3-chloro-1-pentyne by recycling the acid layer

[0061] Put the acid layer obtained in Example 6 into the reaction flask. According to the operation and process conditions of Example 6, recycle it 5 times. As a result, 70 g of the product 3-methyl-3-chloro-1-pentyne is obtained. GC detection confirms that the product content is 96-97% (area normalization), and the calculated yield is 94-95%. The numerical differences within each cycle are small. It can be seen that recycling the acid layer does not affect the preparation of 3-methyl-3-chloro-1-pentyne, and this process is more environmentally friendly.

[0062] Example 8 Preparation of 3-methyl-3-amino-1-pentyne

[0063] Put 50 g (0.73 mol) of 25% ammonia water by mass concentration into the reaction flask, start stirring, cool it to -5 °C in a cold bath, control the temperature at -5 °C to 5 °C, and introduce 12 g (0.70 mol) of ammonia gas into the solution while controlling the temperature at -5-5 °C. Add 3 g of copper(I) chloride as a catalyst. While controlling the temperature at -5 °C to 5 °C, add 50 g (0.42 mol) of the 3-methyl-3-chloro-1-pentyne raw material obtained in Example 1 and introduce 16 g (0.94 mol) of ammonia gas into the solution dropwise within 5 hours. After dropping, keep the temperature at -5 °C to 5 °C and hold for 2 hours.

[0064] After standing and separating layers, 44 g of the upper oil layer and 84 g of the lower ammonia water layer are obtained. Heat the oil layer to 20-25 °C to volatilize the excessive dissolved ammonia gas, and 41 g of the product 3-methyl-3-amino-1-pentyne is obtained.

[0065] The obtained product is confirmed by GC detection to have a content of 95.2% (area normalization method), and the calculated yield is 96.6%.

[0066] Then, through conventional vacuum distillation, 38 g of 3-methyl-3-amino-1-pentyne with a content of 97% and a yield of 91.2% is obtained. It passes the mass spectrometry and nuclear magnetic resonance tests, as Figure 1-2 shown.

[0067] Example 9 Preparation of 3-methyl-3-amino-1-pentyne

[0068] The same procedure as in Example 8 is carried out, except that copper(I) chloride as the catalyst is replaced by silver nitrate, and other conditions and process operations remain unchanged, and the same results are obtained.

[0069] Example 10 Preparation of 3-methyl-3-amino-1-pentyne by recycling the ammonia water layer

[0070] The same procedure as in Example 8 is carried out, except that 84 g of the separated ammonia water layer is recycled to replace the ammonia water used in the reaction, and no additional catalyst is added, and other conditions and process operations remain unchanged, and the same results are obtained.

[0071] Comparative Example 1

[0072] 90 g of 30% industrial hydrochloric acid (0.74 mol) was charged into the reaction flask. Sulfuric acid was not contained in the reaction system. Stirring was started and the mixture was cooled to -5°C in a cold bath. 3 g of cuprous chloride as a catalyst was added. While controlling the temperature at -5°C to 5°C, 60 g (0.60 mol) of 3-methyl-1-pentyn-3-ol raw material and 30 g (0.82 mol) of hydrogen chloride gas were dropped into the solution within 2 hours. After dropping, the mixture was kept at -5°C to 5°C for 2 hours.

[0073] After standing and separating layers, 63 g of the upper oil layer and 120 g of the lower acid layer were obtained. The oil layer was washed with 20 g of water to obtain 60 g of the product 3-methyl-3-chloro-1-pentyne. The content of the product was confirmed to be 92% (area normalization) by GC detection, and the yield was calculated to be 77.5%.

[0074] Comparative Example 2

[0075] 50 g (0.73 mol) of 25% ammonia water by mass concentration was charged into the reaction flask. Stirring was started and the mixture was cooled to -5°C in a cold bath. While controlling the temperature at -5°C to 5°C, 12 g (0.70 mol) of ammonia gas was introduced into the solution. 3 g of cuprous chloride as a catalyst was added. While controlling the temperature at -5°C to 5°C, 50 g (0.42 mol) of the 3-methyl-3-chloro-1-pentyne raw material obtained in Example 1, 16 g (0.94 mol) of ammonia gas and 48 g (0.42 mol) of 35% sodium hydroxide solution were dropped into the solution within 5 hours. After completion, the mixture was kept at -5°C to 5°C for 2 hours.

[0076] After standing and separating layers, 44 g of the upper oil layer and 134 g of the lower ammonia water layer were obtained. The oil layer was heated to 20 - 25°C to volatilize the excessive dissolved ammonia gas, and 40 g of the product 3-methyl-3-amino-1-pentyne was obtained. The content was confirmed to be 85.2% (area normalization) by GC detection, and the yield was calculated to be 84.3%.

[0077] Further, 35 g of 3-methyl-3-amino-1-pentyne with a content of 89% and a yield of 77.0% was obtained through conventional vacuum distillation.

[0078] Comparative Example 3

[0079] The same procedure as in Comparative Example 2 was carried out, except that the catalyst was not added. 35 g of 3-methyl-3-amino-1-pentyne with a content of 85% and a yield of 73.6% was obtained.

[0080] It can be seen that the yield of the product obtained by the preparation method of 35g of 3-methyl-3-amino-1-pentyne of the present invention is significantly higher than that of the prior art. After detection and confirmation, the product content is ≥95%. It does not need to be purified or only needs conventional vacuum distillation to meet the synthesis process of zoxamide, which has environmental and economic significance.

Claims

1. Preparation method of 3-methyl-3-amino-1-pentyne, characterized in that The steps of this method are as follows: (1) In the presence of sulfuric acid, hydrochloric acid and a catalyst, or sulfuric acid, hydrochloric acid and hydrogen chloride gas are introduced and in the presence of a catalyst, 3-methyl-1-pentyn-3-ol undergoes an alkyne chlorination reaction at a temperature of -5°C to 5°C, and 3-methyl-3-chloro-1-pentyne is obtained by separation. The catalyst is copper sulfate or cuprous chloride; the reaction formula is as follows: ； (2) In the presence of ammonia water and ammonia gas is introduced and a catalyst is present, the 3-methyl-3-chloro-1-pentyne obtained in step (1) undergoes an ammoniation reaction at a temperature of -5°C to 5°C, and 3-methyl-3-amino-1-pentyne is obtained by separation; when ammonia gas is introduced, the molar amount of ammonia gas is 1 to 5 times the molar amount of 3-methyl-3-chloro-1-pentyne, and the catalyst is silver nitrate; the reaction formula is as follows: 。 2. The preparation method according to claim 1, wherein In step (1), the mass concentration of sulfuric acid is 50 - 100%, and the molar amount of sulfuric acid is 1.0 - 2.0 times the molar amount of 3-methyl-1-pentyn-3-ol.

3. The preparation method according to claim 1, characterized in that In step (1), the mass concentration of hydrochloric acid is 10 - 40%.

4. The preparation method according to claim 1, characterized in that The weight of the catalyst in steps (1) and (2) is 1 - 10% of the weight of 3-methyl-1-pentyn-3-ol.

5. The preparation method according to claim 1, characterized in that In step (2), the mass concentration of ammonia water is 20 - 50%, and the molar amount of the ammonia water is 2 - 10 times the molar amount of 3-methyl-3-chloro-1-pentyne.

Images