Synthesis method of 1, 4-dichloromethylnaphthalene

Abstract

The invention provides a synthesis method of 1, 4-dichloromethylnaphthalene, which comprises the following steps: S1, uniformly mixing naphthalene, paraformaldehyde, a catalyst I and hydrochloric acid, and heating for reaction to obtain 1-chloromethylnaphthalene; and S2, mixing the 1-chloromethylnaphthalene, a catalyst II and a chloromethylmagnesium chloride Grignard reagent in a reaction solvent, and heating for reaction to obtain the 1, 4-dichloromethylnaphthalene. The chloromethylmagnesium chloride Grignard reagent is introduced in the reaction process, so that the yield and purity of the product are effectively improved, and meanwhile, the problem of product isomerization when Blanc chloromethylation reaction is directly adopted is solved. The yield and purity of the 1, 4-dichloromethylnaphthalene product are effectively improved through a two-step method, the purity of the 1, 4-dichloromethylnaphthalene reaches 98% or above, and the yield can reach 90% or above.

Description

Technical Field

[0001] The invention belongs to the field of chemical industry, in particular to the field of organic synthesis, and relates to a method for synthesizing 1,4-dichloromethylnaphthalene. Background Art

[0002] 1,4-Dichloromethylnaphthalene is a white crystal or powder with a special aromatic smell. It is an important intermediate in organic synthesis and is often used to synthesize other compounds. 1,4-Dichloromethylnaphthalene can be used as a synthetic raw material for dyes, drugs and pesticides, and can also be used for the modification and functionalization of polymers.

[0003] The general preparation method of 1,4-dichloromethylnaphthalene is to react 1,4-dibromonaphthalene in methanol and tetrachloromethane with aluminum trichloride. First, aluminum trichloride is added to tetrachloromethane, and then 1,4-dibromonaphthalene is slowly added, the temperature is controlled at 0-5 degrees Celsius, and the reaction is carried out for 2-3 hours; after the reaction is completed, the reactants are mixed with water and neutralized to obtain the product, which is 1,4-dichloromethylnaphthalene. Although this method has only one step reaction, aluminum trichloride is very easy to absorb water and produce acid mist, the reaction conditions are relatively harsh, and safety is also a problem, and the cost of industrial promotion is high. Chinese patent CN113004110A discloses a method for directly reacting a Grignard reagent to obtain 1,4-dimethylnaphthalene. Referring to this method, the Blanc chloromethylation reaction can be directly used for preparation, but this method not only has a low yield of 1,4-dichloromethylation, but also easily produces isomerization problems, which causes certain difficulties for separation and purification. Summary of the invention

[0004] In view of the drawbacks of the existing preparation methods of 1,4-dimethylnaphthalene, the present invention provides a method for synthesizing 1,4-dichloromethylnaphthalene, which effectively improves the yield and purity of the product and solves the problem of product isomerization.

[0005] The present invention is achieved through the following technical solutions: A method for synthesizing 1,4-dichloromethylnaphthalene, comprising: S1, mixing naphthalene, paraformaldehyde, catalyst I and hydrochloric acid uniformly, heating to react, and obtaining 1-chloromethylnaphthalene; S2, 1-chloromethylnaphthalene, catalyst II and chloromethylmagnesium chloride Grignard reagent are mixed in a reaction solvent, and the temperature is raised to react to obtain 1,4-dichloromethylnaphthalene.

[0006] Preferably, S1 specifically includes: S11, naphthalene, paraformaldehyde, catalyst I and hydrochloric acid are uniformly mixed, the temperature is raised to react, after the reaction is completed, the temperature is lowered and the mixture is allowed to stand for separation, and the obtained oil phase is washed to obtain a crude 1-chloromethylnaphthalene product; S12, adding the crude 1-chloromethylnaphthalene into an alcohol solvent, heating to dissolve, cooling to crystallize, filtering, washing, and drying to obtain 1-chloromethylnaphthalene.

[0007] Furthermore, in S12, the alcohol solvent is one or more of ethanol, methanol and isopropanol.

[0008] Preferably, in S1, the catalyst I is one or more of tetraethylammonium bromide, tetrabutylammonium bromide, benzyltriethylammonium chloride, tetrabutylammonium chloride, zinc chloride, tin tetrachloride and copper chloride.

[0009] Preferably, in S1, the reaction temperature is 90-95° C., and the reaction time is 15-24 h.

[0010] Preferably, in S1, the molar ratio of naphthalene, paraformaldehyde, catalyst I and hydrochloric acid is 1: (1.5-3): (0.01-0.05): (3-6).

[0011] Preferably, S2 specifically comprises: adding 1-chloromethylnaphthalene, catalyst II and reaction solvent into a container in sequence, then dropwise adding chloromethylmagnesium chloride Grignard reagent under the protection of inert gas, heating to react, and after the reaction is completed, distilling to recover the reaction solvent, then adding ethyl acetate and water to extract and separate the phases, and the obtained organic phase is subjected to step-by-step distillation to recover ethyl acetate to obtain a 1,4-dichloromethylnaphthalene product.

[0012] Preferably, in S2, the catalyst II is one or more of nickel dichloride, bis(triphenylphosphine)nickel dichloride, 1,3-bis(diphenylphosphine)propanenickel dichloride and (1,1'-bis(diphenylphosphine)ferrocene)nickel dichloride.

[0013] Preferably, in S2, the reaction temperature is 50-90°C.

[0014] Preferably, in S2, the molar ratio of 1-chloromethylnaphthalene, chloromethylmagnesium chloride Grignard reagent and catalyst II is 1:(1.1-1.3):(0.002-0.005).

[0015] Compared with the prior art, the present invention has the following beneficial effects: The present invention adopts a two-step method to prepare 1,4-dichloromethylnaphthalene, firstly prepares 1-chloromethylnaphthalene, then performs homocyclic α substitution in the presence of a chloromethyl magnesium chloride Grignard reagent, and directly obtains 1,4-dichloromethylnaphthalene. The chloromethyl magnesium chloride Grignard reagent is introduced during the reaction process, which effectively improves the yield and purity of the product, and solves the problem of product isomerization when directly using the Blanc chloromethylation reaction. The present invention effectively improves the yield and purity of the 1,4-dichloromethylnaphthalene product through the two-step method, so that the purity of 1,4-dichloromethylnaphthalene reaches more than 98%, and the yield can reach more than 90%.

[0016] Furthermore, the present invention separates and purifies the prepared crude 1-chloromethylnaphthalene and then reacts it with a Grignard reagent, thereby further improving the purity and yield of the product 1,4-dichloromethylnaphthalene. DETAILED DESCRIPTION

[0017] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0018] It should be noted that the process equipment or devices not specifically specified in the following embodiments are all conventional equipment or devices in the art.

[0019] It should be noted that the terms "include" and "have" and any variations thereof are intended to cover non-exclusive inclusions. For example, a process, method, system, product or device that includes a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices. Moreover, unless otherwise specified, the numbering of each method step is only a convenient tool for identifying each method step, and is not intended to limit the order of arrangement of each method step or to define the scope of the present invention. Changes or adjustments in their relative relationships should also be regarded as the scope of the present invention without substantially changing the technical content.

[0020] The synthesis method of 1,4-dichloromethylnaphthalene of the present invention comprises the following steps: S1, mixing naphthalene, paraformaldehyde, catalyst I and hydrochloric acid uniformly, heating to react, and obtaining 1-chloromethylnaphthalene; S2, mixing 1-chloromethylnaphthalene, catalyst II and chloromethylmagnesium chloride Grignard reagent in a reaction solvent, heating and reacting to obtain 1,4-dichloromethylnaphthalene; The reaction equation is as follows:

[0021] The present invention S1 specifically includes: S11, naphthalene, paraformaldehyde, catalyst I and hydrochloric acid are uniformly mixed, the temperature is raised to react, after the reaction is completed, the temperature is lowered and the mixture is allowed to stand for separation, and the obtained oil phase is washed to obtain a crude 1-chloromethylnaphthalene product; S12, adding the crude 1-chloromethylnaphthalene into an alcohol solvent, heating to dissolve, cooling to crystallize, filtering, washing, and drying to obtain high-purity 1-chloromethylnaphthalene.

[0022] The method of the present invention firstly obtains pure 1-chloromethylnaphthalene, which reduces the cost and also ensures the purity of the raw materials in the next step, so that the yield of 1,4-dichloromethylnaphthalene is greatly improved.

[0023] In S1 of the present invention, the catalyst I is one or more of tetraethylammonium bromide, tetrabutylammonium bromide, benzyltriethylammonium chloride (TEBA), tetrabutylammonium chloride, zinc chloride, tin tetrachloride and copper chloride. Further, the catalyst I is a combination of zinc chloride and tin tetrachloride, and the mass ratio of zinc chloride to tin tetrachloride is 1: (0.1-0.5), more preferably 1:0.3.

[0024] In S1 of the present invention, the molar ratio of naphthalene to paraformaldehyde is 1: (1.5-3), more preferably 1: 2.5; the molar ratio of naphthalene to catalyst is 1: 0.01-0.05, more preferably 1: 0.03; the molar ratio of naphthalene to hydrochloric acid is 1: (3-6), more preferably 1: 4.

[0025] In S1 of the present invention, the reaction temperature is 90-95° C., more preferably 90° C.; the reaction time is 15-24 h, more preferably 20 h.

[0026] In S11 of the present invention, the washing process is washing with water for 3 to 5 times; in S12, the alcohol solvent is one or more of ethanol, methanol and isopropanol, and the mass ratio of the alcohol solvent to the crude 1-chloromethylnaphthalene is 1: (1 to 1.5), more preferably 1: 1.2.

[0027] In S12 of the present invention, specifically, the steps include: dissolving crude 1-chloromethylnaphthalene in an alcohol solvent at 40-50° C., then naturally cooling to about 5° C., and keeping the temperature for 24 hours to obtain pure 1-chloromethylnaphthalene.

[0028] In S2 of the present invention, the preparation method of the chloromethyl magnesium chloride Grignard reagent is: magnesium chips and anhydrous ether are mixed, the temperature is controlled at -8~0°C in an ice-salt bath, ethyl bromide is added to initiate the reaction, 1,2-dichloroethane is added dropwise while stirring, the reaction generates insoluble matter, after the magnesium reaction is completed, the temperature is raised to room temperature, the reaction is continued for 1h, the precipitation is dissolved, and chloromethyl magnesium chloride is obtained.

[0029] Specifically, the preparation method of the chloromethylmagnesium chloride Grignard reagent in the embodiment of the present invention is as follows: 200g (0.3mol) of magnesium chips and 200ml of anhydrous ether are added to a reaction bottle, the temperature is controlled at -8~0°C under an ice-salt bath, 2ml of bromoethane is added to initiate the reaction, 29.7g (0.3mol) of 1,2-dichloroethane is added dropwise while stirring, the reaction generates insoluble matter, after the magnesium reaction is completed, the temperature is raised to room temperature, and the reaction is continued for 1h, the precipitate is dissolved, and chloromethylmagnesium chloride is obtained.

[0030] In S2 of the present invention, the catalyst II is one or more of nickel dichloride, bis(triphenylphosphine)nickel dichloride, 1,3-bis(diphenylphosphine)propanenickel dichloride and (1,1'-bis(diphenylphosphine)ferrocene)nickel dichloride.

[0031] In S2 of the present invention, the reaction solvent is an organic solvent, and the organic solvent is one or more of tetrahydrofuran, toluene, cyclohexane and 1,4-dioxane.

[0032] In S2 of the present invention, the reaction temperature is 50-90°C, preferably 70°C.

[0033] In S2 of the present invention, the molar ratio of 1-chloromethylnaphthalene to chloromethylmagnesium chloride Grignard reagent is 1:(1.1-1.3), preferably 1:1.2; the molar ratio of 1-chloromethylnaphthalene to catalyst II is 1:(0.002-0.005), preferably 1:0.003.

[0034] The present invention S2 specifically comprises: adding 1-chloromethylnaphthalene, catalyst II and reaction solvent into a container in sequence, then slowly dropping chloromethylmagnesium chloride Grignard reagent under the protection of inert gas, heating to react, and after the reaction is completed, distilling and recovering the reaction solvent, then adding ethyl acetate and water to extract and separate the phases, and after the organic phase is distilled step by step to recover ethyl acetate, 1,4-dichloromethylnaphthalene product is obtained.

[0035] Example 1 Preparation of 1-chloromethylnaphthalene: Mix 128 g (1 mol) of naphthalene, 135 g (3 mol) of paraformaldehyde, 6.8 g (0.05 mol) of zinc chloride and 684 g (32 wt.% content, 6 mol) of industrial hydrochloric acid evenly, heat to 95°C and keep the temperature for reaction for 24 hours, cool down, stand and separate the liquids, wash the oil phase with water 3 times to obtain crude 1-chloromethylnaphthalene.

[0036] Purification of 1-chloromethylnaphthalene: 240 g of the crude 1-chloromethylnaphthalene was added to 160 g of anhydrous ethanol, and the temperature was raised to 45° C. to dissolve, and then naturally cooled to 5° C. to crystallize for 24 hours, filtered, and washed with anhydrous ethanol. The filter cake was placed in a vacuum drying oven and dried at 25 mmHg and 30° C. for 6 hours to obtain 214 g of 1-chloromethylnaphthalene product with a content of 99% and a yield of 89.2%.

[0037] Preparation of 1,4-dichloromethylnaphthalene: First, 35.3 g (0.2 mol) of 1-chloromethylnaphthalene, 654 mg (1 mmol) of bis(triphenylphosphine)nickel dichloride, and 200 mL of toluene were added to the reaction bottle in sequence; then, under nitrogen protection, 87 mL (0.26 mol) of chloromethyl magnesium chloride tetrahydrofuran solution was slowly added dropwise while stirring at -10 °C. After the addition, the temperature was raised to 90 °C for reaction for 16 h, and the solvent was distilled to recover the solvent. Then, 100 mL of ethyl acetate and 120 mL of water were added to extract and separate the phases; the organic phase obtained by extraction and separation was distilled to recover ethyl acetate, and the 165 °C fraction was further collected by water pump vacuum distillation, which was 1,4-dichloromethylnaphthalene, and a total of 40.6 g of product was obtained, with a content of 98% and a yield of 90.1%.

[0038] Example 2 Preparation of 1-chloromethylnaphthalene: Mix 128 g (1 mol) of naphthalene, 78.75 g (2.5 mol) of paraformaldehyde, 2.6 g (0.01 mol) of tin tetrachloride and 456 g (32 wt.% content, 4 mol) of industrial hydrochloric acid evenly, heat to 90°C and keep the temperature for reaction for 15 hours, cool down, stand and separate the liquids, wash the oil phase with water 3 times to obtain crude 1-chloromethylnaphthalene.

[0039] Purification of 2-chloromethylnaphthalene: 160 g of the crude 1-chloromethylnaphthalene was added to 160 g of anhydrous ethanol, and the temperature was raised to 45°C to dissolve, and then naturally cooled to 5°C for crystallization for 24 hours, filtered, and washed with anhydrous ethanol. The filter cake was placed in a vacuum drying oven and dried at 25 mmHg and 30°C for 6 hours to obtain 147.2 g of 1-chloromethylnaphthalene product with a content of 99% and a yield of 92%.

[0040] Preparation of 1,4-dichloromethylnaphthalene: First, 35.3 g (0.2 mol) of 1-chloromethylnaphthalene, 165 mg (0.4 mmol) of 1,3-bis(diphenylphosphino)propanenickel dichloride, and 200 mL of anhydrous tetrahydrofuran were added to the reaction bottle in sequence; then, under nitrogen protection, the temperature was controlled to be -10°C with stirring, and 80 mL (0.24 mol) of chloromethylmagnesium chloride tetrahydrofuran solution was slowly added dropwise. After the addition, the temperature was raised to 150°C for reaction for 16 hours, and the solvent was distilled to recover the solvent. Then, 100 mL of ethyl acetate and 120 mL of water were added to extract and separate the phases; the organic phase obtained by extraction and separation was distilled to recover ethyl acetate, and the 165°C fraction was further collected by water pump vacuum distillation, which was 1,4-dichloromethylnaphthalene, and a total of 39.8 g of product was obtained, with a content of 98% and a yield of 88.4%.

[0041] Example 3 Preparation of 1-chloromethylnaphthalene: Mix 128 g (1 mol) of naphthalene, 131.25 g (2.5 mol) of paraformaldehyde, 3.13 g (0.023 mol) of zinc chloride, 1.8 g (0.007 mol) of tin tetrachloride and 456 g (32 wt.% content, 4 mol) of industrial hydrochloric acid evenly, heat to 93 ° C and keep the temperature for reaction for 20 hours, cool down, stand and separate the liquids, wash the oil phase with water 3 times to obtain crude 1-chloromethylnaphthalene.

[0042] Purification of 3-chloromethylnaphthalene: 192 g of the crude 1-chloromethylnaphthalene was added to 160 g of anhydrous ethanol, and the temperature was raised to 45°C to dissolve, and then naturally cooled to 5°C for crystallization for 24 hours, filtered, and washed with anhydrous ethanol. The filter cake was placed in a vacuum drying oven and dried at 25 mmHg and 30°C for 6 hours to obtain 179.3 g of 1-chloromethylnaphthalene product with a content of 99% and a yield of 93.4%.

[0043] Preparation of 1,4-dichloromethylnaphthalene: First, 35.3 g (0.2 mol) of 1-chloromethylnaphthalene, 77.8 mg (0.6 mmol) of nickel dichloride, and 200 mL of anhydrous tetrahydrofuran were added to the reaction bottle in sequence; then, under nitrogen protection, 80 mL (0.24 mol) of chloromethyl magnesium chloride tetrahydrofuran solution was slowly added dropwise while stirring at -10 °C. After the addition, the temperature was raised to 150 °C for reaction for 16 h, and the solvent was distilled to recover the solvent. Then, 100 mL of ethyl acetate and 120 mL of water were added for extraction and separation; the organic phase obtained by extraction and separation was distilled to recover ethyl acetate, and the 165 °C fraction was further collected by water pump vacuum distillation, which was 1,4-dichloromethylnaphthalene, and a total of 42.5 g of product was obtained, with a content of 98% and a yield of 94.4%.

[0044] According to the invention, 1-chloromethylnaphthalene is subjected to homocyclic α substitution in the presence of a chloromethylmagnesium chloride Grignard reagent to directly obtain 1,4-dichloromethylnaphthalene, thereby solving the problem of product isomerization when 1,4-dimethylnaphthalene is directly subjected to a Blanc chloromethylation reaction, and effectively improving the yield and purity of the 1,4-dichloromethylnaphthalene product.

[0045] The above contents are only for explaining the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. A method for synthesizing 1,4-dichloromethylnaphthalene, characterized in that: include: S1, mixing naphthalene, paraformaldehyde, catalyst I and hydrochloric acid uniformly, heating and reacting to obtain 1-chloromethylnaphthalene; S2, 1-chloromethylnaphthalene, catalyst II and chloromethylmagnesium chloride Grignard reagent are mixed in a reaction solvent, and the temperature is raised to react to obtain 1,4-dichloromethylnaphthalene.

2. The method for synthesizing 1,4-dichloromethylnaphthalene according to claim 1, characterized in that: S1 specifically includes: S11, naphthalene, paraformaldehyde, catalyst I and hydrochloric acid are uniformly mixed, the temperature is raised to react, after the reaction is completed, the temperature is lowered and the mixture is allowed to stand for separation, and the obtained oil phase is washed to obtain a crude 1-chloromethylnaphthalene product; S12, adding the crude 1-chloromethylnaphthalene into an alcohol solvent, heating to dissolve, cooling to crystallize, filtering, washing, and drying to obtain 1-chloromethylnaphthalene.

3. The method for synthesizing 1,4-dichloromethylnaphthalene according to claim 2, characterized in that: In S12, the alcohol solvent is one or more of ethanol, methanol and isopropanol.

4. The method for synthesizing 1,4-dichloromethylnaphthalene according to claim 1, characterized in that: In S1, the catalyst I is one or more of tetraethylammonium bromide, tetrabutylammonium bromide, benzyltriethylammonium chloride, tetrabutylammonium chloride, zinc chloride, tin tetrachloride and copper chloride.

5. The method for synthesizing 1,4-dichloromethylnaphthalene according to claim 1, characterized in that: In S1, the reaction temperature is 90-95°C and the reaction time is 15-24h.

6. The method for synthesizing 1,4-dichloromethylnaphthalene according to claim 1, characterized in that: In S1, the molar ratio of naphthalene, polyformaldehyde, catalyst I and hydrochloric acid is 1: (1.5~3): (0.01~0.05): (3~6).

7. The method for synthesizing 1,4-dichloromethylnaphthalene according to claim 1, characterized in that: S2 specifically includes: adding 1-chloromethylnaphthalene, catalyst II and reaction solvent into a container in sequence, then dropwise adding chloromethylmagnesium chloride Grignard reagent under the protection of inert gas, heating to react, and after the reaction is completed, distilling to recover the reaction solvent, then adding ethyl acetate and water to extract and separate the phases, and after the obtained organic phase is distilled step by step to recover ethyl acetate, 1,4-dichloromethylnaphthalene product is obtained.

8. The method for synthesizing 1,4-dichloromethylnaphthalene according to claim 1, characterized in that: In S2, the catalyst II is one or more of nickel dichloride, bis(triphenylphosphine)nickel dichloride, 1,3-bis(diphenylphosphine)propanenickel dichloride and (1,1'-bis(diphenylphosphine)ferrocene)nickel dichloride.

9. The method for synthesizing 1,4-dichloromethylnaphthalene according to claim 1, characterized in that: In S2, the reaction temperature is 50~90°C.

10. The method for synthesizing 1,4-dichloromethylnaphthalene according to claim 1, characterized in that: In S2, the molar ratio of 1-chloromethylnaphthalene, chloromethylmagnesium chloride Grignard reagent and catalyst II is 1: (1.1~1.3): (0.002~0.005).

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