Tubular production method of monosubstituted alkynyl tertiary alcohol

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a method for tubular production of monosubstituted alkynyl tertiary alcohol, which comprises the following steps: 1) in an oxygen-free environment, adding magnesium chips and an initiator into an organic solvent, stirring and heating to 30-50 DEG C, adding an organic solution of halogenated alkane, and reacting for 25-50 minutes to obtain an alkyl magnesium halide mixed solution; 2) in an oxygen-free environment, continuously introducing acetylene gas into the organic solvent, dropwise adding the alkyl magnesium halide mixed solution into the organic solvent, reacting at 30-60 DEG C to obtain an ethynyl magnesium halide mixed solution, and stopping introducing the acetylene gas; and 3) in an oxygen-free environment, dropwise adding an organic solution of ketone into the ethynyl magnesium halide mixed solution which is heated to 45-60 DEG C, continuously reacting for 1-3 hours after dropwise adding is finished, and adding an acidic compound for quenching to obtain a target product. The monoalkynol with different structures is prepared by the same method, the whole process adopts a closed series process, intermediate products do not need to be treated, the process flow is simple, the safety is relatively high, the process production cost can be reduced, and the like, and industrial production is facilitated.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a tubular method for producing monosubstituted alkynyl tertiary alcohols. Background Technology

[0002] Monosubstituted alkynols are commonly used as specialty surfactants, such as wetting agents, dispersants, and defoamers, and are widely applied in pharmaceutical intermediates, coatings, printing and dyeing, and metal plating. Depending on the preparation process, their preparation methods mainly fall into two categories: alkaline catalysis (such as potassium hydroxide, potassium isobutoxide, etc.) and traditional alkynyl metal reagent addition methods.

[0003] The base-catalyzed method typically uses stoichiometric potassium hydroxide or potassium isobutoxide as reaction promoters to react with acetylene gas in an organic solvent (such as methyl tert-butyl ether, toluene, cyclohexane, etc.) via an adsorption-type acid-base reaction to obtain a highly reactive potassium acetylene intermediate. This intermediate then undergoes an addition reaction with ketones (such as acetone, methyl isobutyl ketone, methyl isopentyl ketone, etc.) to yield propargyl alcohols. However, this method usually yields disubstituted acetylene alcohols as the main product, making selective control of mono-acetylene alcohol synthesis difficult, with yields typically below 20%. Although some studies have shown that increasing the acetylene pressure (>3.0 MPa) can significantly improve the selectivity of mono-acetylene alcohols, the safety risks are extremely high, making operation difficult and severely limiting its industrial economic viability.

[0004] Traditional alkynyl metal reagent addition methods typically use dissolved magnesium alkynyl (usually dissolved in ether solvents such as tetrahydrofuran) as the acetylenic group source, which directly reacts with ketone compounds (such as acetone, methyl isobutyl ketone, methyl isopentyl ketone, etc.) to selectively yield monoalkynyl alcohols. Chinese invention application CN201410127669.7 discloses a method for preparing propargyl alcohol using a microstructured reactor. In the first step, a Grignard exchange reaction is performed between a Grignard reagent and acetylene gas to generate acetylenyl magnesium bromide Grignard reagent. In the second step, under continuous flow conditions, the acetylenyl magnesium bromide Grignard reagent undergoes a nucleophilic addition reaction with an electrophilic reagent in another microstructured reactor, ultimately yielding the target product, propargyl alcohol. However, because the magnesium alkynyl compound in this method is sensitive to water and oxygen, it is not suitable for long-term storage, and the method increases operational difficulty and safety risks, thus hindering the scale-up and large-scale production of the reaction.

[0005] Chinese invention patent application CN202010490080.9 discloses a method for the continuous and rapid preparation of propargyl alcohols using a microreactor. This method uses alkyl halides or aryl halides as raw materials to prepare the corresponding Grignard reagents, which undergo Grignard exchange reactions to obtain ethynylmagnesium bromide. Subsequently, a nucleophilic addition reaction is performed with formaldehyde to finally obtain the target product, propargyl alcohol. However, reports on the preparation of structurally different mono-alkynyl alcohols from simple raw materials by directly ethynylating different types of ketones are rare. Therefore, it is necessary to design a universal method for the synthesis of mono-alkynyl alcohols. Summary of the Invention

[0006] The purpose of this invention is to provide a tubular method for producing monosubstituted alkynyl tertiary alcohols, so as to achieve the production of monoalkynyl alcohols with different structures by the same method.

[0007] To achieve the above objectives, the present invention provides a method for tubular production of monosubstituted alkynyl tertiary alcohols, comprising the following steps: S1. Add magnesium shavings and initiator to reactor I, replace the air in reactor I with an inert gas, add organic solvent, stir and heat to 30-50°C, add organic solution of haloalkanes, react for 25-50 min to obtain alkyl magnesium halide mixture; S2. Replace the air in reactor II with an inert gas, add an organic solvent, and continuously pass acetylene gas into the organic solvent. Then, add the alkyl magnesium halide mixture obtained in step S1 into reactor II and react at 30-60°C to obtain an acetylene-based magnesium halide mixture. Stop passing acetylene gas. S3. Replace the air in reactor III with an inert gas, add the acetylene-based magnesium halide mixture obtained in step S2 into reactor III, heat to 45-60°C, add an organic solution of ketone dropwise, continue the reaction for 1-3 hours after the addition is complete, add an acidic compound to quench the reaction, and obtain the target product by extraction, separation, rotary evaporation concentration, and vacuum distillation.

[0008] Optionally, in step S1, the concentration of the organic solution of haloalkanes is 1-2 mol / L, and the organic solution of haloalkanes is added to reactor I by dropwise addition at a rate of 10-20 mL / h.

[0009] Optionally, in step S2, the alkyl magnesium halide mixture is added to reactor II by dropwise addition.

[0010] Optionally, in step S2, the reaction is carried out at 30–60°C for 0.5–1.0 h.

[0011] Optionally, in step S3, the dropping rate of the organic solution of the ketone is 10–20 mL / h.

[0012] Optionally, in step S3, the molar ratio of ketone to acetylenyl magnesium halide is 1:1.1 to 3.0.

[0013] Optionally, in step S3, the ketone is an aryl ketone, an alkyl ketone, or an alkenyl unsaturated ketone.

[0014] Optionally, in step S3, the target product contains a monosubstituted alkynyl tertiary alcohol, the structure of which is shown in formula (I): ; In equation (Ⅰ), R 1 and R 2 Each is independently selected from alkyl, substituted alkyl, aryl, and alkenyl groups, or, R 1 R 2 The carbon atoms attached to the hydroxyl group form a ring, and R 1 and R 2 The sum of the number of carbon atoms is ≥2.

[0015] Optionally, in steps S1, S2 and S3, the organic solvent is tetrahydrofuran.

[0016] Optionally, reactor I, reactor II, and reactor III are all tubular reactors.

[0017] The working principle and beneficial effects of this scheme are as follows: In this scheme, from the introduction of haloalkanes into reactor I to the quenching in reactor III to obtain alkynol compounds, the entire process adopts a closed-loop series process. Intermediate products require no treatment, the process flow is simplified, safety is relatively high, and it is time-saving and efficient. Furthermore, reactors I, II, and III are all tubular reactors, enabling the application of the acetylation reaction of ketones to prepare monoalkynols from the laboratory to industrial production levels. In addition, this scheme has universality; different ketone compounds can be used as reaction substrates to synthesize monoalkynols with different structures, achieving the production of monoalkynols with different structures using the same method, with a maximum yield of up to 82.2%. Attached Figure Description

[0018] Figure 1 This is a process flow diagram of the production equipment for a tubular production method of monosubstituted alkynyl tertiary alcohols according to Embodiment 1 of the present invention; Figure 2 This is a gas chromatogram of the product 3,5-dimethyl-1-hexyn-3-ol in Example 1 of the present invention; Figure 3 The NMR spectrum of 3,5-dimethyl-1-hexyn-3-ol, the product of Example 1 of this invention; Figure 4 This is a gas chromatogram of the product 2-methyl-3-butyn-2-ol in Example 2 of the present invention; Figure 5The NMR spectrum of 2-methyl-3-butyn-2-ol, the product of Example 2 of this invention; Figure 6 This is the gas chromatogram of the product 3,6-dimethyl-1-heptyne-3-ol in Example 3 of the present invention; Figure 7 The NMR spectrum of 3,6-dimethyl-1-heptyne-3-ol, the product of Example 3 of this invention; Figure 8 This is the gas chromatogram of 1-ethynylcyclohexanol, the product in Example 4 of the present invention; Figure 9 The NMR spectrum of 1-ethynylcyclohexanol, the product in Example 4 of this invention; Figure 10 This is the gas chromatogram of the product 2-phenyl-3-butyn-2-ol in Example 5 of the present invention; Figure 11 The NMR spectrum of 2-phenyl-3-butyn-2-ol, the product of Example 5 of this invention. Detailed Implementation

[0019] The embodiments of the present invention are illustrated below through specific examples. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0020] Example 1 This embodiment provides a method for synthesizing 3,5-dimethyl-1-hexyn-3-ol, which includes the following steps: (1) 0.48 g of activated magnesium shavings and a small amount of elemental iodine were added to reactor I after it had been treated with ultra-drying. After replacing the air in reactor I with nitrogen three times, 10 mL of ultra-dry tetrahydrofuran solvent was added using a syringe. The stirring was started and the reaction system was heated to 40 °C. 2.20 g of bromoethane was dissolved in 10 mL of ultra-dry tetrahydrofuran and then added dropwise to reactor I using a syringe pump at a rate of 10 mL / h. After the reaction was initiated, the heating was stopped and the reaction was stirred at room temperature. After the magnesium shavings had reacted completely, the stirring was stopped to obtain a mixture of alkyl magnesium bromide.

[0021] (2) After the air in reactor II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the alkyl magnesium bromide mixture obtained in step (1) is slowly transferred dropwise into reactor II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. oThe reaction was carried out at C for 1.0 h. After the reaction solution completely changed from dark gray to light yellow, the acetylene gas was stopped, and a mixture of acetylene-based magnesium bromide was obtained.

[0022] (3) After the air in reactor III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the acetylenyl magnesium bromide mixture obtained in step (2) is added to reactor III, and the temperature is raised to 45°C. 1.00 g of methyl isobutyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reactor III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and vacuum distillation, 1.09 g of the target product is obtained.

[0023] In the above process, the reaction between bromoethane and magnesium filings is exothermic, and the color of the reaction solution gradually changes from anhydrous to dark gray. When acetylene is introduced into the reaction solution, a slight exothermic reaction occurs, and the color gradually changes from dark gray to light yellow. During the addition of methyl isobutyl ketone, the color of the reaction solution gradually changes from light yellow to pale yellow until it becomes clear and transparent.

[0024] The target product obtained in this embodiment was detected, and its gas chromatogram after distillation is shown below. Figure 2 As shown, its NMR spectrum is as follows: Figure 3 As shown, the target product in this embodiment is verified to be 3,5-dimethyl-1-hexyn-3-ol. In this embodiment, the total yield of the crude product is 86.3%, and the purity is 88.6%; the combined yield of the three-step product after distillation is 76.5%, and the purity is 99.6%.

[0025] In addition, reactors I, II, and III are laboratory three-necked flasks, but can also be tubular reactors. When tubular reactors are used, the process flow diagram of the production equipment is as follows: Figure 1 As shown in the diagram. During the reaction, the haloalkanes are heated (40°C) in a preheater and then enter reactor I (the first-stage tubular reactor). There, they undergo a Grignard reaction with excess magnesium shavings (reactor I is pre-filled with magnesium shavings and an initiator) to obtain alkyl Grignard reagents. The alkyl Grignard reagent filtrate is premixed with acetylene gas in a mixer and then enters reactor II (the second-stage packed tower microreactor) for an acetylene exchange reaction (at 30°C) to obtain an acetylenoid magnesium halide solution. The acetylenoid magnesium halide solution is then mixed with a preheated (45°C) ketone in a micromixer and enters reactor III (the third-stage tubular reactor) to react, yielding the final product containing the target product (monoyne alcohol). All volatile organic compounds (VOCs) generated during the entire process are collected and centrally treated.

[0026] Example 2 This embodiment provides a method for synthesizing 2-methyl-3-butyn-2-ol, which includes the following steps: (1) 0.48 g of activated magnesium shavings and a small amount of elemental iodine were added to reactor I after it had been treated with ultra-drying. After replacing the air in reactor I with nitrogen three times, 10 mL of ultra-dry tetrahydrofuran solvent was added using a syringe. The stirring was started and the reaction system was heated to 40 °C. 2.20 g of bromoethane was dissolved in 10 mL of ultra-dry tetrahydrofuran and then added dropwise to reactor I using a syringe pump at a rate of 10 mL / h. After the reaction was initiated, the heating was stopped and the reaction was stirred at room temperature. After the magnesium shavings had reacted completely, the stirring was stopped to obtain a mixture of alkyl magnesium bromide.

[0027] (2) After the air in reactor II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the alkyl magnesium bromide mixture obtained in step (1) is slowly transferred dropwise into reactor II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 1.0 h. After the reaction solution completely changed from dark gray to light yellow, the acetylene gas was stopped, and a mixture of acetylene-based magnesium bromide was obtained.

[0028] (3) After the air in reactor III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the acetylenyl magnesium bromide mixture obtained in step (2) is added to reactor III, and the temperature is raised to 45°C. 0.58 g of acetone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reactor III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and vacuum distillation, 0.69 g of the target product is obtained.

[0029] In the above process, the reaction between bromoethane and magnesium filings is exothermic, and the color of the reaction solution gradually changes from anhydrous to dark gray. When acetylene is introduced into the reaction solution, a slight exothermic reaction occurs, and the color gradually changes from dark gray to light yellow. During the addition of acetone, the color of the reaction solution gradually changes from light yellow to pale yellow until it becomes clear and transparent.

[0030] The target product obtained in this embodiment was detected, and its gas chromatogram after distillation is shown below. Figure 4 As shown, its NMR spectrum is as follows: Figure 5 As shown, the target product in this embodiment is verified to be 2-methyl-3-butyn-2-ol. In this embodiment, the total yield of the crude product is 92.3%, and the purity is 89.2%; the combined yield of the product after distillation is 82.2%, and the purity is 99.9%.

[0031] Example 3 This embodiment provides a method for synthesizing 3,6-dimethyl-1-heptyne-3-ol, which includes the following steps: (1) 0.36 g of activated magnesium shavings and a small amount of elemental iodine were added to reactor I after it had been treated with ultra-drying. After replacing the air in reactor I with nitrogen three times, 10 mL of ultra-dry tetrahydrofuran solvent was added using a syringe. The stirring was started and the reaction system was heated to 40 °C. 1.70 g of bromoethane was dissolved in 10 mL of ultra-dry tetrahydrofuran and then added dropwise to reactor I using a syringe pump at a rate of 10 mL / h. After the reaction was initiated, the heating was stopped and the reaction was stirred at room temperature. After the magnesium shavings had reacted completely, the stirring was stopped to obtain a mixture of alkyl magnesium bromide.

[0032] (2) After the air in reactor II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the alkyl magnesium bromide mixture obtained in step (1) is slowly transferred dropwise into reactor II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 1.0 h. After the reaction solution completely changed from dark gray to light yellow, the acetylene gas was stopped, and a mixture of acetylene-based magnesium bromide was obtained.

[0033] (3) After the air in reactor III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the acetylenyl magnesium bromide mixture obtained in step (2) is added to reactor III and the temperature is raised to 45°C. 1.40 g of methyl isopentyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran and then added dropwise to reactor III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and vacuum distillation, 1.11 g of the target product is obtained.

[0034] In the above process, the reaction between bromoethane and magnesium filings is exothermic, and the color of the reaction solution gradually changes from anhydrous to dark gray. When acetylene is introduced into the reaction solution, a slight exothermic reaction occurs, and the color gradually changes from dark gray to light yellow. During the addition of methyl isopentyl ketone, the color of the reaction solution gradually changes from light yellow to pale yellow until it becomes clear and transparent.

[0035] The target product obtained in this embodiment was detected, and its gas chromatogram after distillation is shown below. Figure 6 As shown, its NMR spectrum is as follows: Figure 7As shown, the target product in this embodiment is verified to be 3,6-dimethyl-1-heptyne-3-ol. In this embodiment, the total yield of the crude product is 91.9%, and the purity is 76.2%; the combined yield of the three-step product after distillation is 79.3%, and the purity is 80.7%.

[0036] Example 4 This embodiment provides a method for synthesizing 1-ethynylcyclohexanol, which includes the following steps: (1) 0.53 g of activated magnesium shavings and a small amount of elemental iodine were added to reactor I after it had been treated with ultra-drying. After replacing the air in reactor I with nitrogen three times, 10 mL of ultra-dry tetrahydrofuran solvent was added using a syringe. The stirring was started and the reaction system was heated to 40 °C. 2.40 g of bromoethane was dissolved in 10 mL of ultra-dry tetrahydrofuran and then added dropwise to reactor I using a syringe pump at a rate of 10 mL / h. After the reaction was initiated, the heating was stopped and the reaction was stirred at room temperature. After the magnesium shavings had reacted completely, the stirring was stopped to obtain a mixture of alkyl magnesium bromide.

[0037] (2) After the air in reactor II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the alkyl magnesium bromide mixture obtained in step (1) is slowly transferred dropwise into reactor II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 1.0 h. After the reaction solution completely changed from dark gray to light yellow, the acetylene gas was stopped, and a mixture of acetylene-based magnesium bromide was obtained.

[0038] (3) After the air in reactor III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the acetylenyl magnesium bromide mixture obtained in step (2) is added to reactor III, and the temperature is raised to 60°C. 0.98 g of cyclohexanone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reactor III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 2.0 h. After the reaction is completed, the reaction is quenched with a 13% hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and vacuum distillation, 0.96 g of the target product is obtained.

[0039] In the above process, the reaction between bromoethane and magnesium filings is exothermic, and the color of the reaction solution gradually changes from anhydrous to dark gray. When acetylene is introduced into the reaction solution, a slight exothermic reaction occurs, and the color gradually changes from dark gray to light yellow. During the addition of cyclohexanone, the color of the reaction solution gradually changes from light yellow to pale yellow until it becomes clear and transparent.

[0040] The target product obtained in this embodiment was detected, and its gas chromatogram after distillation is shown below. Figure 8 As shown, its NMR spectrum is as follows: Figure 9 As shown, the target product in this embodiment is verified to be 1-ethynylcyclohexanol. In this embodiment, the total yield of the crude product is 89.2%, and the purity is 88.0%; the combined yield of the three-step product after distillation is 78.5%, and the purity is 99.4%.

[0041] Example 5 This embodiment provides a method for synthesizing 2-phenyl-3-butyn-2-ol, which includes the following steps: (1) 0.48 g of activated magnesium shavings and a small amount of elemental iodine were added to reactor I after it had been treated with ultra-drying. After replacing the air in reactor I with nitrogen three times, 10 mL of ultra-dry tetrahydrofuran solvent was added using a syringe. The stirring was started and the reaction system was heated to 40 °C. 2.20 g of bromoethane was dissolved in 10 mL of ultra-dry tetrahydrofuran and then added dropwise to reactor I using a syringe pump at a rate of 10 mL / h. After the reaction was initiated, the heating was stopped and the reaction was stirred at room temperature. After the magnesium shavings had reacted completely, the stirring was stopped to obtain a mixture of alkyl magnesium bromide.

[0042] (2) After the air in reactor II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the alkyl magnesium bromide mixture obtained in step (1) is slowly transferred dropwise into reactor II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 1.0 h. After the reaction solution completely changed from dark gray to light yellow, the acetylene gas was stopped, and a mixture of acetylene-based magnesium bromide was obtained.

[0043] (3) After the air in reactor III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the acetylenyl magnesium bromide mixture obtained in step (2) is added to reactor III, and the temperature is raised to 60°C. 1.20 g of acetophenone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reactor III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 3.0 h. After the reaction is completed, the reaction is quenched with a 13% hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and vacuum distillation, 1.05 g of the target product is obtained.

[0044] In the above process, the reaction between bromoethane and magnesium filings is exothermic, and the color of the reaction solution gradually changes from anhydrous to dark gray. When acetylene is introduced into the reaction solution, a slight exothermic reaction occurs, and the color gradually changes from dark gray to light yellow. During the addition of acetophenone, the color of the reaction solution gradually changes from light yellow to pale yellow until it becomes clear and transparent.

[0045] The target product obtained in this embodiment was detected, and its gas chromatogram after distillation is shown below. Figure 10 As shown, its NMR spectrum is as follows: Figure 11 As shown, the target product in this embodiment is verified to be 2-phenyl-3-butyn-2-ol. In this embodiment, the total yield of the crude product is 85.6%, and the purity is 84.3%; the combined yield of the product after distillation is 71.8%, and the purity is 93.9%.

[0046] Example 6 This embodiment provides a ( E A method for synthesizing 3-methyl-1-phenylpent-1-en-4-yne-3-ol, the method comprising the following steps: (1) 0.60 g of activated magnesium shavings and a small amount of elemental iodine were added to reactor I after it had been treated with ultra-drying. After replacing the air in reactor I with nitrogen three times, 10 mL of ultra-dry tetrahydrofuran solvent was added using a syringe. The stirring was started and the reaction system was heated to 40 °C. 2.70 g of bromoethane was dissolved in 10 mL of ultra-dry tetrahydrofuran and then added dropwise to reactor I using a syringe pump at a rate of 10 mL / h. After the reaction was initiated, the heating was stopped and the reaction was stirred at room temperature. After the magnesium shavings had reacted completely, the stirring was stopped to obtain a mixture of alkyl magnesium bromide.

[0047] (2) After the air in reactor II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the alkyl magnesium bromide mixture obtained in step (1) is slowly transferred dropwise into reactor II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 1.0 h. After the reaction solution completely changed from dark gray to light yellow, the acetylene gas was stopped, and a mixture of acetylene-based magnesium bromide was obtained.

[0048] (3) After the air in reactor III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the acetylenyl magnesium bromide mixture obtained in step (2) is added to reactor III and the temperature is raised to 45°C. 1.46 g of trans-4-phenyl-3-buten-2-one is dissolved in 10 mL of ultra-dry tetrahydrofuran and then added dropwise to reactor III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 3.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and vacuum distillation, 0.96 g of the target product is obtained.

[0049] In the above process, the reaction between bromoethane and magnesium shavings is exothermic, and the color of the reaction solution gradually changes from anhydrous to dark gray. When acetylene is introduced into the reaction solution, a slight exothermic reaction occurs, and the color gradually changes from dark gray to light yellow. During the dropwise addition of trans-4-phenyl-3-buten-2-one, the color of the reaction solution gradually changes from light yellow to pale yellow until it becomes clear and transparent.

[0050] The target product obtained in this embodiment was detected to be ( E The crude product yielded 66.9% and had a purity of 85.3%; the combined yield of the three-step distillation product was 56.5% and had a purity of 96.2%.

[0051] Examples 7-12 Examples 7-12 were synthesized using the method described in Example 1, with the only difference being the choice of ketone. The choice of ketone and the purity and yield of the target product are shown in Table 1.

[0052] Table 1. Selection of ketones and detection results of target products in Examples 7-12

[0053] Comparative Example 1 This comparative example provides a method for synthesizing 3,6-dimethyl-1-heptyne-3-ol, which includes the following steps: (1) Add 0.36 g of activated magnesium shavings and two iodine particles to a 100 mL three-necked reaction flask I that has been treated with ultra-drying. After replacing the air in the reaction flask with nitrogen three times, add 10 mL of ultra-dry tetrahydrofuran solvent using a syringe, start stirring and heat the reaction system to 20 °C. Dissolve 1.70 g of bromoethane in 10 mL of ultra-dry tetrahydrofuran, and then add it dropwise to reaction flask I using a syringe pump at a rate of 10 mL / h. Keep stirring at 20 °C for 30 min to obtain mixture I.

[0054] (2) After the air in the three-necked reaction flask II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the mixture I obtained in step (1) is slowly transferred dropwise into reaction flask II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 1.0 h. After the reaction solution completely changed from dark gray to light yellow, the acetylene gas was stopped, and mixture II was obtained.

[0055] (3) After the air in reaction flask III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the mixture II obtained in step (2) is added to reaction flask III, and the temperature is raised to 45°C. 1.40 g of methyl isopentyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reaction flask III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and concentration, and vacuum distillation, 0.32 g of the target product is obtained.

[0056] In this comparative example, the target product was 3,6-dimethyl-1-heptyne-3-ol. The total recovery rate of the crude product was 26.48%, and the purity was 64.3%. The overall three-step yield of the product after distillation was 15.56%, and the purity was 76.3%.

[0057] Comparative Example 2 This comparative example provides a method for synthesizing 3,6-dimethyl-1-heptyne-3-ol, which includes the following steps: (1) Add 0.36 g of activated magnesium shavings and two iodine particles to a 100 mL three-necked reaction flask I that has been treated with ultra-drying. After replacing the air in the reaction flask with nitrogen three times, add 10 mL of ultra-dry tetrahydrofuran solvent using a syringe, start stirring and heat the reaction system to 70 °C. Dissolve 1.70 g of bromoethane in 10 mL of ultra-dry tetrahydrofuran, and then add it dropwise to reaction flask I using a syringe pump at a rate of 10 mL / h. Keep stirring at 20 °C for 30 min to obtain mixture I.

[0058] (2) After the air in the three-necked reaction flask II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the mixture I obtained in step (1) is slowly transferred dropwise into reaction flask II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 1.0 h. After the reaction solution completely changed from dark gray to light yellow, the acetylene gas was stopped, and mixture II was obtained.

[0059] (3) After the air in reaction flask III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the mixture II obtained in step (2) is added to reaction flask III, and the temperature is raised to 45°C. 1.40 g of methyl isopentyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reaction flask III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and concentration, and vacuum distillation, 0.58 g of the target product is obtained.

[0060] In this comparative example, the target product was 3,6-dimethyl-1-heptyne-3-ol. The total recovery rate of the crude product was 48.12%, and the purity was 66.3%. The overall three-step yield of the product after distillation was 36.95%, and the purity was 75.7%.

[0061] Comparative Example 3 This comparative example provides a method for synthesizing 3,6-dimethyl-1-heptyne-3-ol, which includes the following steps: (1) Add 0.36 g of activated magnesium shavings and two iodine particles to a 100 mL three-necked reaction flask I that has been treated with ultra-drying. After replacing the air in the reaction flask with nitrogen three times, add 10 mL of ultra-dry tetrahydrofuran solvent using a syringe, start stirring and heat the reaction system to 40 °C. Dissolve 1.70 g of bromoethane in 10 mL of ultra-dry tetrahydrofuran, and then add it dropwise to reaction flask I using a syringe pump at a rate of 10 mL / h. After the reaction is initiated, stop heating and stir the reaction at room temperature for 10 min to obtain mixture I.

[0062] (2) After the air in the three-necked reaction flask II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the mixture I obtained in step (1) is slowly transferred dropwise into reaction flask II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 1.0 h. After the reaction solution completely changed from dark gray to light yellow, the acetylene gas was stopped, and mixture II was obtained.

[0063] (3) After the air in reaction flask III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the mixture II obtained in step (2) is added to reaction flask III, and the temperature is raised to 45°C. 1.40 g of methyl isopentyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reaction flask III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and concentration, and vacuum distillation, 0.56 g of the target product is obtained.

[0064] In this comparative example, the target product was 3,6-dimethyl-1-heptyne-3-ol. The total recovery rate of the crude product was 46.41%, and the purity was 68.4%. The overall three-step yield of the product after distillation was 35.49%, and the purity was 77.5%.

[0065] Comparative Example 4 This comparative example provides a method for synthesizing 3,6-dimethyl-1-heptyne-3-ol, which includes the following steps: (1) Add 0.36 g of activated magnesium shavings and two iodine particles to a 100 mL three-necked reaction flask I that has been treated with ultra-drying. After replacing the air in the reaction flask with nitrogen three times, add 10 mL of ultra-dry tetrahydrofuran solvent using a syringe, start stirring and heat the reaction system to 40 °C. Dissolve 1.70 g of bromoethane in 10 mL of ultra-dry tetrahydrofuran, and then add it dropwise to reaction flask I using a syringe pump at a rate of 10 mL / h. After the reaction is initiated, stop heating and stir the reaction at room temperature for 90 min to obtain mixture I.

[0066] (2) After the air in the three-necked reaction flask II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the mixture I obtained in step (1) is slowly transferred dropwise into reaction flask II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 1.0 h. After the reaction solution completely changed from dark gray to light yellow, the acetylene gas was stopped, and mixture II was obtained.

[0067] (3) After the air in reaction flask III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the mixture II obtained in step (2) is added to reaction flask III, and the temperature is raised to 45°C. 1.40 g of methyl isopentyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reaction flask III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and concentration, and vacuum distillation, 0.39 g of the target product is obtained.

[0068] In this comparative example, the target product was 3,6-dimethyl-1-heptyne-3-ol. The total recovery rate of the crude product was 32.25%, and the purity was 67.5%. The overall three-step yield of the product after distillation was 23.70%, and the purity was 75.8%.

[0069] Comparative Example 5 This comparative example provides a method for synthesizing 3,6-dimethyl-1-heptyne-3-ol, which includes the following steps: (1) Add 0.36 g of activated magnesium shavings and two iodine particles to a 100 mL three-necked reaction flask I that has been treated with ultra-drying. After replacing the air in the reaction flask with nitrogen three times, add 10 mL of ultra-dry tetrahydrofuran solvent using a syringe. Start stirring and heat the reaction system to 40 °C. Dissolve 1.70 g of bromoethane in 10 mL of ultra-dry tetrahydrofuran, and then add it dropwise to reaction flask I using a syringe pump at a rate of 10 mL / h. After the reaction is initiated, stop heating and stir the reaction at room temperature. Stop stirring after the magnesium shavings have reacted completely to obtain mixture I.

[0070] (2) After the air in the three-necked reaction flask II, which has been treated with ultra-drying, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added with a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the mixture I obtained in step (1) is slowly transferred and added dropwise to the reaction flask II under a slight positive pressure with a needle, and acetylene gas is continuously introduced. The reaction is carried out at 20°C for 1.0 h, and the introduction of acetylene gas is stopped to obtain mixture II.

[0071] (3) After the air in reaction flask III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the mixture II obtained in step (2) is added to reaction flask III, and the temperature is raised to 45°C. 1.40 g of methyl isopentyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reaction flask III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and concentration, and vacuum distillation, 0.26 g of the target product is obtained.

[0072] In this comparative example, the target product was 3,6-dimethyl-1-heptyne-3-ol. The total recovery rate of the crude product was 21.52%, and the purity was 64.6%. The overall three-step yield of the product after distillation was 12.03%, and the purity was 77.2%.

[0073] Comparative Example 6 This comparative example provides a method for synthesizing 3,6-dimethyl-1-heptyne-3-ol, which includes the following steps: (1) Add 0.36 g of activated magnesium shavings and a small amount of iodine to a 100 mL three-necked reaction flask I that has been treated with ultra-drying. After replacing the air in the reaction flask with nitrogen three times, add 10 mL of ultra-dry tetrahydrofuran solvent using a syringe. Start stirring and heat the reaction system to 40 °C. Dissolve 1.70 g of bromoethane in 10 mL of ultra-dry tetrahydrofuran, and then add it dropwise to reaction flask I using a syringe pump at a rate of 10 mL / h. After the reaction is initiated, stop heating and stir the reaction at room temperature. Stop stirring after the magnesium shavings have reacted completely to obtain mixture I.

[0074] (2) After the air in the three-necked reaction flask II, which has been treated with ultra-drying, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added with a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the mixture I obtained in step (1) is slowly transferred and added dropwise to the reaction flask II under a slight positive pressure with a needle, and acetylene gas is continuously introduced. The reaction is carried out at 70°C for 1.0 h, and the introduction of acetylene gas is stopped to obtain mixture II.

[0075] (3) After the air in reaction flask III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the mixture II obtained in step (2) is added to reaction flask III and cooled to 45°C. 1.40 g of methyl isopentyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran and then added dropwise to reaction flask III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and vacuum distillation, 0.41 g of the target product is obtained.

[0076] In this comparative example, the target product was 3,6-dimethyl-1-heptyne-3-ol. The total recovery rate of the crude product was 34.03%, and the purity was 66.1%. The overall three-step yield of the product after distillation was 28.95%, and the purity was 76.9%.

[0077] Comparative Example 7 This comparative example provides a method for synthesizing 3,6-dimethyl-1-heptyne-3-ol, which includes the following steps: (1) Add 0.36 g of activated magnesium shavings and a small amount of iodine to a 100 mL three-necked reaction flask I that has been treated with ultra-drying. After replacing the air in the reaction flask with nitrogen three times, add 10 mL of ultra-dry tetrahydrofuran solvent using a syringe. Start stirring and heat the reaction system to 40 °C. Dissolve 1.70 g of bromoethane in 10 mL of ultra-dry tetrahydrofuran, and then add it dropwise to reaction flask I using a syringe pump at a rate of 10 mL / h. After the reaction is initiated, stop heating and stir the reaction at room temperature. Stop stirring after the magnesium shavings have reacted completely to obtain mixture I.

[0078] (2) After the air in the three-necked reaction flask II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the mixture I obtained in step (1) is slowly transferred dropwise into reaction flask II under a slight positive pressure using a needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 10 min, and then the acetylene gas was stopped to obtain mixture II.

[0079] (3) After the air in reaction flask III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the mixture II obtained in step (2) is added to reaction flask III, and the temperature is raised to 45°C. 1.40 g of methyl isopentyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reaction flask III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and concentration, and vacuum distillation, 0.56 g of the target product is obtained.

[0080] In this comparative example, the target product was 3,6-dimethyl-1-heptyne-3-ol. The total recovery rate of the crude product was 58.16%, and the purity was 65.9%. The overall three-step yield of the product after distillation was 48.64%, and the purity was 77.0%.

[0081] Comparative Example 8 This comparative example provides a method for synthesizing 3,6-dimethyl-1-heptyne-3-ol, which includes the following steps: (1) Add 0.36 g of activated magnesium shavings and a small amount of iodine to a 100 mL three-necked reaction flask I that has been treated with ultra-drying. After replacing the air in the reaction flask with nitrogen three times, add 10 mL of ultra-dry tetrahydrofuran solvent using a syringe. Start stirring and heat the reaction system to 40 °C. Dissolve 1.70 g of bromoethane in 10 mL of ultra-dry tetrahydrofuran, and then add it dropwise to reaction flask I using a syringe pump at a rate of 10 mL / h. After the reaction is initiated, stop heating and stir the reaction at room temperature. Stop stirring after the magnesium shavings have reacted completely to obtain mixture I.

[0082] (2) After the air in the three-necked reaction flask II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the mixture I obtained in step (1) is slowly transferred dropwise into reaction flask II under a slight positive pressure using a needle, and acetylene gas is continuously introduced. o The reaction was carried out at C for 90 min, and then the acetylene gas was stopped to obtain mixture II.

[0083] (3) After the air in reaction flask III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the mixture II obtained in step (2) is added to reaction flask III, and the temperature is raised to 45°C. 1.40 g of methyl isopentyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reaction flask III at a rate of 10 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% dilute hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and concentration, and vacuum distillation, 0.17 g of the target product is obtained.

[0084] In this comparative example, the target product was 3,6-dimethyl-1-heptyne-3-ol. The total recovery rate of the crude product was 14.07%, and the purity was 64.2%. The overall yield of the product after distillation was 10.73%, and the purity was 74.2%.

[0085] Comparative Example 9 This comparative example provides a method for synthesizing 3,6-dimethyl-1-heptyne-3-ol, which includes the following steps: (1) Add 0.36 g of activated magnesium shavings and a small amount of iodine to a 100 mL three-necked reaction flask I that has been treated with ultra-drying. After replacing the air in the reaction flask with nitrogen three times, add 10 mL of ultra-dry tetrahydrofuran solvent using a syringe. Start stirring and heat the reaction system to 40 °C. Dissolve 1.70 g of bromoethane in 10 mL of ultra-dry tetrahydrofuran, and then add it dropwise to reaction flask I using a syringe pump at a rate of 10 mL / h. After the reaction is initiated, stop heating and stir the reaction at room temperature. Stop stirring after the magnesium shavings have reacted completely to obtain mixture I.

[0086] (2) After the air in the three-necked reaction flask II, which has undergone ultra-drying treatment, is replaced with nitrogen three times, 5.0 mL of ultra-dry tetrahydrofuran solvent is added using a syringe, and acetylene gas is slowly introduced under a slight positive pressure. After 10 min, the mixture I obtained in step (1) is slowly transferred dropwise into reaction flask II under a slight positive pressure using a double-ended needle, and acetylene gas is continuously introduced. o The reaction was carried out under C conditions for 1.0 h, and the acetylene gas was stopped to obtain mixture II.

[0087] (3) After the air in reaction flask III, which has undergone ultra-drying treatment, is replaced with nitrogen three times, the mixture II obtained in step (2) is added to reaction flask III, and the temperature is raised to 45°C. 1.40 g of methyl isopentyl ketone is dissolved in 10 mL of ultra-dry tetrahydrofuran, and then added dropwise to reaction flask III at a rate of 30 mL / h using a syringe pump. After the addition is completed, the reaction continues for 1.0 h. After the reaction is completed, the reaction is quenched with a 13% hydrochloric acid solution, and the organic phase is extracted three times with ethyl acetate and water. After drying, rotary evaporation and concentration, and vacuum distillation, 1.08 g of the target product is obtained.

[0088] In this comparative example, the target product was 3,6-dimethyl-1-heptyne-3-ol. The total recovery rate of the crude product was 90.09%, and the purity was 65.7%. The overall three-step yield of the product after distillation was 77.04%, and the purity was 76.2%.

[0089] The above are merely embodiments of the present invention. The invention is not limited to the fields covered by these embodiments. Commonly known structures and characteristics are not described in detail here. Those skilled in the art are aware of all common technical knowledge in the field prior to the application date or priority date, are aware of all existing technologies in that field, and have the ability to apply conventional experimental methods prior to that date. Those skilled in the art can improve and implement this solution based on the guidance provided in this application and their own capabilities. Some typical known structures or methods should not be obstacles for those skilled in the art to implement this application. It should be noted that those skilled in the art can make several modifications and improvements without departing from the structure of the present invention. These should also be considered within the scope of protection of the present invention, and will not affect the effectiveness or practicality of the invention. The scope of protection claimed in this application should be determined by the content of its claims. The specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A process for the tubular production of monosubstituted alkynyl tertiary alcohols, characterized in that: The method comprises the following steps: S1, adding magnesium chips and an initiator into a reactor I, replacing air in the reactor I with inert gas, adding an organic solvent, stirring and heating to 30-50 DEG C, adding an organic solution of halogenated alkane, and reacting for 25-50 min to obtain an alkyl magnesium halide mixture; S2, replacing air in a reactor II with inert gas, adding an organic solvent, continuously introducing acetylene gas into the organic solvent, then adding the alkyl magnesium halide mixture obtained in step S1 into the reactor II, and reacting at 30-60 DEG C to obtain an ethynyl magnesium halide mixture, and stopping the introduction of acetylene gas; S3, replacing air in a reactor III with inert gas, adding the ethynyl magnesium halide mixture obtained in step S2 into the reactor III, heating to 45-60 DEG C, adding an organic solution of ketone dropwise, continuing to react for 1-3 h after the dropwise addition is completed, adding an acidic compound to quench, and performing extraction, liquid separation, rotary evaporation, concentration, and reduced pressure distillation to obtain a target product.

2. The process for the tubular production of a monosubstituted terminal alkynyl tertiary alcohol according to claim 1, characterized in that: In step S1, the concentration of the organic solution of halogenated alkane is 1-2 mol / L, and the organic solution of halogenated alkane is added into the reactor I in a dropwise manner, and the dropwise addition speed is 10-20 mL / h.

3. The process for the tubular production of a monosubstituted terminal alkynyl tertiary alcohol according to claim 1, characterized in that: In step S2, the alkyl magnesium halide mixture is added into the reactor II in a dropwise manner.

4. The process for the tubular production of a monosubstituted terminal alkynyl tertiary alcohol according to claim 1, characterized in that: In step S2, the reaction is performed at 30-60 DEG C for 0.5-1.0 h.

5. The process for the tubular production of a monosubstituted terminal alkynyl tertiary alcohol according to claim 1, characterized in that: In step S3, the dropwise addition speed of the organic solution of ketone is 10-20 mL / h.

6. The process for the tubular production of a monosubstituted terminal alkynyl tertiary alcohol according to claim 1, characterized in that: In step S3, the molar ratio of ketone to ethynyl magnesium halide is 1:1.1-3.

0.

7. The process for the tubular production of a monosubstituted terminal alkynyl tertiary alcohol according to claim 1, characterized in that: In step S3, the ketone is an aryl ketone, an alkyl ketone, or an alkenyl unsaturated ketone.

8. The process for the tubular production of a monosubstituted terminal alkynyl tertiary alcohol according to claim 1, characterized in that: In step S3, the target product contains a monosubstituted ethynyl tertiary alcohol, and the structure of the monosubstituted ethynyl tertiary alcohol is shown in formula (I): ； In formula (I), R 1 and R 2 are each independently selected from the group consisting of alkyl, substituted alkyl, aryl, and alkenyl, or R 1 and R 2 together with the carbon atom to which they are attached form a ring, and the sum of the number of carbon atoms of R 1 and R 2 is > 2.

9. The process for the tubular production of a monosubstituted terminal alkynyl tertiary alcohol according to claim 1, characterized in that: In steps S1, S2, and S3, the organic solvent is tetrahydrofuran.

10. The process for the tubular production of a monosubstituted terminal alkynyl tertiary alcohol according to claim 1, characterized in that: The reactor I, the reactor II, and the reactor III are all tubular reactors.

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