阅读说明：本技术 一种3,3-二甲基-1-丁炔的制备方法 (Preparation method of 3,3-dimethyl-1-butyne ) 是由 李太同 朱义胜 尚林峰 昝金行 于 2020-12-29 设计创作，主要内容包括：本发明公开了一种3,3-二甲基-1-丁炔的制备方法,该方法以简单易得、价格便宜的叔丁醇和乙炔为起始原料,以市场上易得的过渡金属的盐为催化剂,在酸存在下直接反应得到产物,经简单的蒸馏分离得高纯产物,该方法操作简便、对环境污染少、产品质量好、收率高、成本低,更适合于工业化生产。(The invention discloses a preparation method of 3,3-dimethyl-1-butyne, which takes tert-butyl alcohol and acetylene which are easy to obtain and low in price as starting raw materials, takes transition metal salt which is easy to obtain in the market as a catalyst, directly reacts in the presence of acid to obtain a product, and obtains a high-purity product through simple distillation and separation.)

1. A preparation method of 3,3-dimethyl-1-butyne is characterized by comprising the following steps:

1) adding tert-butyl alcohol, a catalyst, an organic acid and water into a reaction kettle, and cooling to-5 ℃;

2) replacing air in the reaction kettle in the step 1) with nitrogen, introducing pure acetylene gas into the reaction kettle, replacing the air in the reaction kettle for 3 times, introducing the pure acetylene gas to 0.3-0.5MP, and reacting for 2-3h at 0 ℃ in the kettle until no acetylene is absorbed;

3) introducing nitrogen to replace air in the reaction kettle and exhausting air;

4) transferring the materials in the reaction kettle, distilling at normal pressure, and collecting the fraction at 37-40 ℃ to obtain the 3, 3-dimethyl-1-butyne.

2. The preparation method of claim 1, wherein the catalyst in step 1) is one of nickel sulfate, cobalt sulfate, mercury sulfate, ferric sulfate, rhodium sulfate and ruthenium sulfate in a molar ratio of (2-8): 1 in the composition of claim 1.

3. The method according to claim 1, wherein the organic acid in step 1) is one of methanesulfonic acid, trifluoromethanesulfonic acid and trifluoroacetic acid.

4. The method according to claim 1, wherein the molar ratio of the organic acid to t-butanol in step 1) is (0.05-0.3): 1.

5. The method according to claim 1, wherein the molar ratio of the organic acid to water in step 1) (1-5): (1-5).

6. The process according to claim 1, wherein the molar ratio of catalyst to water (20-21) in step 1) is: (490-500).

7. The method according to claim 1, wherein the pure acetylene gas is prepared in step 2) by a method comprising: taking acetylene gas, and carrying out pretreatment for removing impurities by using a 40% sodium hydroxide solution, a concentrated sulfuric acid solution and an anhydrous calcium chloride drying agent to obtain pure acetylene gas.

Technical Field

The invention relates to a preparation method of 3,3-dimethyl-1-butyne, belonging to the field of chemical synthesis.

Background

Terbinafine hydrochloride is an allylamine antifungal drug, has broad-spectrum antifungal activity and strong antibacterial effect, can kill and inhibit bacteria, has the MIC almost equal to MFC, and can be widely applied to the treatment of various skin fungal diseases, particularly onychomycosis. Terbinafine is currently the only antifungal agent available both externally and orally, and it has an effect on most pathogenic fungi, the most sensitive of which is dermatophytes.

3,3-dimethyl-1-butyne is an important intermediate of antifungal terbinafine hydrochloride. English name is 3, 3-Dimethyl-1-butyl, CAS number is 917-92-0, molecular formula is C₆H₁₀Molecular weight is 82.14, and structural formula is:

the literature reports the synthesis process of 3,3-dimethyl-1-butyne, and the synthesis process mainly comprises the following steps:

Hsing-Pang Hsieh et al reported a method for synthesizing 3, 3-dimethyl-1-butyl (Hsieh H P, Chen A C, Villarante N R, et al. Substistent effects on the photographic arrangement of unsystematic and substistent diene [ J ]. RSC Advances,2012,3(4): 1165-. The method uses pinacolone as a starting material, a mixture of 2, 2-dichloro-3, 3-dimethylbutane and 1, 2-dichloro-3, 3-dimethylbutane is obtained through chlorination of phosphorus pentachloride, and then 3, 3-dimethyl-1-butene is obtained through dechlorination of strong base in DMSO, a large amount of water is required to be added in the treatment after the step 1 in the route, the wastewater contains a large amount of phosphide and chloride, the treatment is difficult, the solvent DMSO in the step 2 is not easy to recover, a large amount of inorganic salt is generated, the three-waste treatment cost is high, and the method is contrary to the national green environmental protection advocated.

Chenweiping and the like report a synthetic route using vinyl chloride and chloro-tert-butane as raw materials (Chenweiping, Liulilin, Yang Ji autumn. Synthesis of antifungal drug terbinafine [ J ]. J. China journal of medical industry, 1989(2):49-52.), firstly, under the catalysis of trichloro-chloride, introducing vinyl chloride gas into chloro-tert-butane to react to obtain 1, 1-dichloro-3, 3-dimethylbutane, then using DMOS as a solvent, and dechlorinating in the presence of potassium hydroxide to obtain a product. The starting raw materials of the route are also low in price, the yield is reported to be 63.14% in literature, the product cost is low, but the problems of large amount of three wastes and difficult treatment exist, and the route is not good for environmental protection.

A synthetic route to 3, 3-dimethyl-1-butene was reported by Kazakov et al (Alkylation of ethylene by tert-butyl alcohol [ J ]. Russian Chemical Bulletin,2002,51(11): 2134-. In the presence of 70% sulfuric acid, acetylene is led into tert-butyl alcohol to react to obtain 3,3-dimethyl-1-butyne, but the literature reports that although the conversion rate of the tert-butyl alcohol can reach 42%, the main product is diisobutylene, and the yield of the 3, 3-dimethyl-1-butene is only 2.1%

Disclosure of Invention

The invention overcomes the defects of the prior art and provides a preparation method of 3,3-dimethyl-1-butyne, which takes tert-butyl alcohol and acetylene which are easy to obtain and have low price as starting materials, takes transition metal salt which is easy to obtain in the market as a catalyst, directly reacts in the presence of acid to obtain a product, and obtains a high-purity product through simple distillation and separation. The synthetic route is as follows:

a preparation method of 3,3-dimethyl-1-butyne comprises the following steps:

1) adding tert-butyl alcohol, a catalyst, an organic acid and water into a reaction kettle, and cooling to-5 ℃;

2) replacing air in the reaction kettle in the step 1) with nitrogen, introducing pure acetylene gas into the reaction kettle, replacing the air in the reaction kettle for 3 times, introducing the pure acetylene gas to 0.3-0.5MP, and reacting for 2-3h at 0 ℃ in the kettle until no acetylene is absorbed;

3) introducing nitrogen to replace air in the reaction kettle and exhausting air;

4) transferring the materials in the reaction kettle, distilling at normal pressure, and collecting the fraction at 37-40 ℃ to obtain the 3, 3-dimethyl-1-butyne.

Further, the catalyst in the step 1) is (2-8) of the molar ratio of one of nickel sulfate, cobalt sulfate, mercury sulfate, ferric sulfate, rhodium sulfate and ruthenium sulfate to palladium sulfate: 1 in the composition of claim 1.

Further, the organic acid in the step 1) is one of methanesulfonic acid, trifluoromethanesulfonic acid and trifluoroacetic acid.

Further, the molar ratio of the organic acid to the tert-butanol in the step 1) is (0.05-0.3): 1.

Further, the molar ratio (1-5) of the organic acid to the water in the step 1) is: (1-5).

Further, the molar ratio (20-21) of the catalyst to water in the step 1) is: (490-500).

Further, the preparation method of the pure acetylene gas in the step 2) comprises the following steps: taking acetylene gas, and carrying out pretreatment for removing impurities by using a 40% sodium hydroxide solution, a concentrated sulfuric acid solution and an anhydrous calcium chloride drying agent to obtain pure acetylene gas.

Has the advantages that:

(1) the 3, 3-dimethyl-1-butene is prepared by directly adopting simple, easily obtained and low-cost tert-butyl alcohol to react with acetylene, and the catalyst, organic acid and water used in the reaction are not easy to volatilize and can be repeatedly used for many times.

(2) The invention has the advantages of short synthetic route, simple and easily obtained raw materials, no reactant or other organic solvent except the catalyst, mild reaction conditions, simple post-treatment, good product quality and high yield.

(3) After the product is obtained by normal pressure distillation in the method, the residual materials can be recycled by vacuum concentration at 80 ℃, three wastes are less, the method is environment-friendly, and the method is suitable for industrial production.

Detailed Description

In order to make the technical solutions in the present application better understood, the present invention is further described below with reference to examples, which are only a part of examples of the present application, but not all examples, and the present invention is not limited by the following examples.

Example 1

Example 1: preparation of 3,3-dimethyl-1-butyne

Tert-butyl alcohol and acetylene are used as starting materials, transition metal salt which is easily obtained in the market is used as a catalyst, the reaction is directly carried out in the presence of acid to obtain a product, and the high-purity product is obtained through simple distillation separation, wherein the synthetic route is as follows:

adding 1000ml (10.5mol) of tert-butyl alcohol, 4.7g (0.018mol) of nickel sulfate hexahydrate, 0.6g (0.003mol) of palladium sulfate, 101g (1.05mol) of methanesulfonic acid and 9g (0.5mol) of deionized water into a 2L high-pressure tetrafluoro autoclave with a lining, cooling to-5 ℃, replacing air in the autoclave with nitrogen, introducing acetylene into the autoclave for replacing the air in the autoclave for 3 times through 40% sodium hydroxide solution, concentrated sulfuric acid solution and anhydrous calcium chloride desiccant respectively, introducing acetylene to 0.5MP, keeping the temperature in the autoclave at 0 ℃ for reaction for 3h until acetylene is not washed, replacing the air in the autoclave with nitrogen, discharging the air, detecting the content of the tert-butyl alcohol in the reaction solution by GC (gas chromatography), transferring the material into a 2L four-mouth bottle, distilling at normal pressure, removing front cut fraction, collecting 778.0g of colorless liquid at 37-40 ℃, wherein the colorless liquid is 3,3-dimethyl-1-butyne, the yield is 90.2%, the product purity was 99.4% (GC method).

Example 2: recycling of residues in the preparation of 3,3-dimethyl-1-butyne

The distillation residue of example 1 was distilled under reduced pressure at-0.09 Mp with an external temperature of 80 ℃ to remove no distillate and to give a total of 122.5g of a brownish red solid-liquid mixture, which was then flushed with 1000ml of tert-butanol into a 2L tetrafluoro-lined autoclave and reacted with acetylene as in example 1 without further addition of catalyst, methanesulfonic acid and water to give a total of 781.2g of a colorless liquid in a yield of 90.7% and a product purity of 99.4% (GC method).

Example 3: preparation of 3,3-dimethyl-1-butyne

Adding 1000ml (10.5mol) of tert-butyl alcohol, 7.2g (0.018mol) of ferric sulfate, 0.6g (0.003mol) of palladium sulfate, 101g (1.05mol) of methanesulfonic acid and 9g (0.5mol) of deionized water into a 2L high-pressure tetrafluoro autoclave with an inner lining, cooling to-5 ℃, firstly replacing air in the autoclave with nitrogen, then respectively leading acetylene gas to pass through 40% sodium hydroxide solution, introducing a concentrated sulfuric acid solution and an anhydrous calcium chloride drying agent into a reaction kettle to replace gas in the kettle for 3 times, introducing acetylene to 0.5MP, keeping the temperature in the kettle at 0 ℃ for reaction for 3 hours until the acetylene is not washed, replacing the gas in the kettle with nitrogen, discharging air, detecting the content of tert-butyl alcohol in a reaction solution by GC (gas chromatography) to be less than or equal to 2 percent, transferring the material to a 2L four-mouth bottle, distilling at normal pressure, removing front fraction, collecting the fraction at 37-40 ℃ to obtain 553.3g of colorless liquid which is 3,3-dimethyl-1-butyne, wherein the yield is 64.0 percent, and the product purity is 99.2 percent (GC method).

Examples 4 to 7: preparation of 3,3-dimethyl-1-butyne

The same reaction as in example 1 was carried out by replacing the nickel sulfate in example 1 with equal molar amounts of cobalt sulfate, mercury sulfate, rhodium sulfate and ruthenium sulfate, respectively, and the results are shown in the following Table 1:

TABLE 1 cases of products prepared in examples 4-7

Example name	Catalyst combination	3, 3-dimethyl-1-butene yield	Product purity (GC)
				Example 4	Cobalt sulfate/palladium sulfate	72.3％	99.1％
Example 5	Mercury/palladium sulfate	77.2％	99.0％
				Example 6	Rhodium/palladium sulfate	91.1％	99.5％
Example 7	Ruthenium sulfate/palladium sulfate	90.9％	99.4％

Example 8: preparation of 3,3-dimethyl-1-butyne

A total of 775.3g of 3,3-dimethyl-1-butyne were obtained in 89.9% yield and a product purity of 99.3% with an equimolar amount of trifluoromethanesulfonic acid instead of methanesulfonic acid as in example 1

Example 9: preparation of 3,3-dimethyl-1-butyne

A total of 752.6g of 3,3-dimethyl-1-butyne were obtained in 87.4% yield and a product purity of 99.5% by replacing methanesulfonic acid in example 1 with an equimolar amount of trifluoroacetic acid.