A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials

Abstract

The invention discloses a low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials, and belongs to the field of organic synthesis. The invention can obtain a target product primary amine with high purity by fully reacting formaldehyde and ammonia in an alcohol solution at a ratio of 8 mol:8 mol, adding 3 mol of halogenated hydrocarbons at a suitable temperature for full reaction, and then undergoing a series of post-treatments. Compared with the classic organic reaction Delépine synthesis method, this method uses less raw materials, produces less by-product acetal and inorganic ammonia, has a simpler synthesis process, and the yield of the target product can generally reach more than 80%. Therefore, it is a low-carbon and environmentally friendly green synthesis method, and is an application and extension of the Delépine synthesis method.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials. Background Art

[0002] It is well known that there are many methods for synthesizing amine compounds. Among them, the most common methods using halogenated hydrocarbons as main raw materials are: Gabriel synthesis method and Delépine synthesis method. Another method is to directly react with a large excess of ammonia to obtain the target product.

[0003] Gabriel synthesis method: This method requires polar solvents such as DMF, potassium phthalimide, hydrazine hydrate, etc. as main raw materials. The market price of raw materials is relatively high, resulting in high cost of products. In addition, the process is relatively complicated, and the separation and purification of the products is relatively troublesome.

[0004] Delépine synthesis method: This method is to react halogenated hydrocarbons with 1-1.1 times the amount of hexamethylenetetramine in a solvent such as chloroform to generate quaternary ammonium salts. After separating and removing the solvent chloroform, the quaternary ammonium salts are hydrolyzed in methanol (or ethanol) with an amount of 12 times the amount of halogenated hydrocarbons and an acid with an amount of 3 times the amount of halogenated hydrocarbons to generate the ammonium salt of the target product, acetal with an amount of 6 times the amount of halogenated hydrocarbons, and inorganic ammonium salt with an amount of 3 times the amount of halogenated hydrocarbons. After separating and removing the acetals, the target product primary amine is obtained by adjusting with alkali. Although the raw material cost of this method is lower than that of the Gabriel synthesis method, a large amount of acetals and inorganic ammonia with low recovery value will be produced during the synthesis process, resulting in a waste of resources and bringing pressure to environmental protection treatment. In addition, the quaternary ammonium salts are first reacted in chloroform, and then the chloroform must be separated, which increases the complexity of the operation process.

[0005] The reaction formula is as follows:

[0006]

[0007] Direct reaction with excess ammonia: Because the target product primary amine is very easy to react with the raw material halogenated hydrocarbon to form secondary amine, tertiary amine, and even quaternary ammonium salt, the ammonia used as the raw material must be greatly excessive. However, even so, a small amount of secondary amine and tertiary amine and other by-products will still be generated, resulting in low purity of the target product primary amine and difficulty in separation. This method is suitable for the synthesis of amines such as primary amine, secondary amine, and tertiary amine that are all worth recycling and can be separated from each other. Summary of the invention

[0008] In view of the problems existing in the prior art, the purpose of the present invention is to provide a low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials, which is specifically achieved through the following technical solutions:

[0009] A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials, the method comprising the following steps:

[0010] 1) Place formaldehyde or paraformaldehyde and a sufficient amount of alcohol solvent into a four-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, add ammonia water dropwise under ice-water cooling and stirring, control the temperature at 0°C to reflux temperature until the mixture is completely dissolved and continue stirring for 0 to 2 hours;

[0011] 2) Add halogenated hydrocarbon dropwise to a four-necked flask, stir and heat in a water bath, and react for 0.5 to 24 hours at a temperature between 20°C and reflux temperature;

[0012] 3) After the reaction is completed, cool slightly, control the temperature at 0-60°C, stir and dropwise add 0.9A-1.5A equivalent of inorganic acid or organic acid, where A refers to: the amount of ammonia contained in ammonia water - the amount of halogenated hydrocarbon, add a small amount of water if necessary, and stir the reaction at 0-60°C for 0.5-10 hours;

[0013] 4) Remove the reflux condenser and replace it with a distillation apparatus. If necessary, add an appropriate amount of water until all the organic solvent is evaporated, and then post-process to obtain the finished primary amine.

[0014] Furthermore, in step 1), the temperature is preferably controlled at 15 to 30° C.; the alcohol solvent is preferably selected from methanol or ethanol, and the stirring time after dissolution is preferably continued for 20 to 60 minutes.

[0015] If paraformaldehyde is used as the raw material, the amount of paraformaldehyde should be converted into the amount of formaldehyde.

[0016] Furthermore, the molar ratio of the reactants is 1.0:1.0-10.0:2.0-10.0, and the amount of ammonia contained in the ammonia water is greater than or equal to the amount of formaldehyde.

[0017] The amount of alcohol added should be sufficient to ensure that the reaction mixture is in a solution state after the halogenated hydrocarbon is added dropwise in the subsequent step 2). The actual amount used varies depending on the halogenated hydrocarbon. Since the alcohol not only serves as a solvent, but also acts as a reactant to react with the formaldehyde produced during the hydrolysis process to form acetal to remove formaldehyde when hydrochloric acid is added subsequently, the amount used should be at least twice the amount of formaldehyde.

[0018] Furthermore, the molar ratio of ammonia contained in the halogenated hydrocarbon: formaldehyde: ammonia water is preferably 1.0:2.6-3.2:2.6-3.5, and the amount of ammonia contained in the ammonia water is ≧the amount of formaldehyde.

[0019] Furthermore, in step 2), after the halogenated hydrocarbon is added dropwise, the temperature of the water bath heating is preferably 30 to 65° C.; and the sufficient reaction time is preferably 1 to 12 hours.

[0020] Further, in step 3), the appropriate temperature is preferably controlled at 20-50°C, the amount of acid added is preferably 1.0A-1.3A, wherein A refers to: the amount of ammonia contained in aqueous ammonia - the amount of halogenated hydrocarbon, the acid is preferably hydrochloric acid among inorganic acids, and the stirring reaction time is preferably 1-5 hours.

[0021] The purpose of adding a small amount of water is to dissolve a small amount of substances that cannot be completely soluble and to form a uniform solution. For example, after adding hydrochloric acid, all substances can form a uniform solution, then there is no need to add water at this time.

[0022] Further, in step 4), the distillation device adopts atmospheric distillation or reduced pressure distillation. For some materials with poor thermal stability, the reduced pressure distillation method can be used to reduce the temperature for protection;

[0023] The appropriate amount of water means that the amount of water added is sufficient to dissolve the ammonium chloride precipitated in the later stage of distillation so that all the organic solvents can be distilled out normally.

[0024] The distilled solvent is mainly alcohol and acetal and a small amount of water. After separation, most of the alcohol can be recovered. When the technology of the present invention is industrialized, the recovered alcohol can be used as the solvent for the next batch of reactions.

[0025] Further, in step 4), the post-processing adopts the following different methods, specifically:

[0026] Method A: After the distillation residue is cooled slightly, it is adjusted to strong alkalinity with an aqueous solution of 0.9B to 1.5B equivalent of alkali metal or alkaline earth metal hydroxide, and the stratification is allowed to stand. The water layer is extracted with a suitable extractant and then enters an environmental protection treatment system. The extract and the oil layer are combined, and the water is removed and then vacuum distilled. The appropriate fraction is collected to obtain the finished primary amine;

[0027] Method B: Cool the distillation residue with ice water to crystallize, vacuum filter to dryness, adjust the obtained crystals to strong alkalinity with 0.9B to 1.5B equivalent of alkali metal or alkaline earth metal hydroxide aqueous solution, let stand to separate, extract the water layer with a suitable extractant and then enter the environmental protection treatment system, combine the extract and the oil layer, remove the water and then conduct vacuum distillation, collect the suitable fraction to obtain the finished primary amine;

[0028] Method C: The distillation residue is adjusted to a strong alkalinity by method A or method B, and then subjected to steam distillation. The distillate is allowed to stand for stratification, the water layer is extracted with a suitable extractant and then enters an environmental treatment system, the extract and the oil layer are combined, the water is removed, and then vacuum distillation is performed, and the appropriate fractions are collected to obtain the finished primary amine;

[0029] In the above methods, B refers to: the amount of the acid substance added + the amount of the halogenated hydrocarbon substance; the extractant is an ether substance or a homologue of benzene or a partially halogenated hydrocarbon.

[0030] Furthermore, the aqueous solution of the alkali metal or alkaline earth metal hydroxide is preferably a sodium hydroxide aqueous solution or a potassium hydroxide aqueous solution; the usage amount is preferably 1.0B to 1.3B, wherein B refers to: the amount of the acid substance added + the amount of the halogenated hydrocarbon substance;

[0031] The ether material is preferably any one of ethyl ether, propyl ether, isopropyl ether, butyl ether, methyl tert-butyl ether, and anisole; the benzene homologue is preferably any one of benzene, toluene, and xylene; the partial halogenated hydrocarbon is preferably dichloromethane;

[0032] The method for removing moisture is: drying with an inorganic salt and filtering to remove moisture, wherein the inorganic salt is preferably any one of anhydrous potassium carbonate, anhydrous sodium carbonate, and anhydrous sodium sulfate;

[0033] Alternatively, the extractant and water can form an azeotropic mixture, which can be heated to reflux and the water can be separated using a water separator.

[0034] The principle of the present invention is as follows:

[0035] In an alcohol solvent, when the ratio of formaldehyde (or polyformaldehyde, which must be converted into formaldehyde) to ammonia is 1 mol:1 mol, the following reaction will occur to generate the cyclic compound 1,3,5-hexahydrotriazine, which is a reversible reaction.

[0036]

[0037] When the amount of ammonia is insufficient, especially when the ratio of formaldehyde to ammonia is 6 mol:4 mol, the following reaction will occur to produce hexamethylenetetramine, which is also a reversible reaction.

[0038]

[0039] If the initial feed of formaldehyde and ammonia is 8 mol each, then a maximum of 8 / 3 mol of the cyclic compound 1,3,5-hexahydrotriazine can be formed in the solution. If a halogenated hydrocarbon is added at this time, the following reaction will occur:

[0040]

[0041] Or it can be expressed by the following reaction formula:

[0042]

[0043] When 1 mol of halogenated hydrocarbon reacts, 1 / 3 mol of 1,3,5-trialkylhexahydrotriazine can be generated, and 1 mol of ammonia will be consumed to form 1 mol of inorganic ammonium halide, so that the ratio of formaldehyde and ammonia in the reaction system becomes: 7 mol: 6 mol. At this time, due to the insufficient amount of ammonia, there is a tendency to form cage-like hexamethylenetetramine in the reaction system.

[0044] When 2 mol of halogenated hydrocarbons react, 2 / 3 mol of 1,3,5-trialkylhexahydrotriazine can be generated, and 2 mol of ammonia will be consumed to form 2 mol of inorganic ammonium halide, so that the ratio of formaldehyde and ammonia in the reaction system becomes: 6 mol:4 mol. At this time, 1 mol of hexamethylenetetramine can be formed, and this 1 mol of hexamethylenetetramine can form a quaternary ammonium salt with 1 mol of halogenated hydrocarbons.

[0045] Therefore, when 8 mol of formaldehyde and 8 mol of ammonia are dissolved and reacted in an alcohol solution, 3 mol of halogenated hydrocarbons are added for full reaction to form 2 / 3 mol of 1,3,5-trialkylhexahydrotriazine and 1 mol of the above-mentioned N-alkylhexamethylenetetramine quaternary ammonium salt.

[0046]

[0047] Under the action of acid and alcohol, 1 mol of the above quaternary ammonium salt is hydrolyzed according to the principle of Delépine synthesis to convert into 1 mol of the ammonium salt of the target product, 6 mol of acetal and 3 mol of inorganic ammonium salt, and 2 / 3 mol of 1,3,5-trialkylhexahydrotriazine is also converted into 2 mol of the ammonium salt of the target product and 2 mol of acetal according to a similar principle.

[0048]

[0049] The target product ammonium salt is separated by distillation to remove acetal, and then subjected to various post-treatments and adjusted to strong alkalinity with alkaline solution, and separated and purified to obtain the finished primary amine.

[0050] RNH2.H + +OH - →RNH2+H2O

[0051] The overall reaction steps of the present invention can be summarized as follows:

[0052] 1. 8 mol of formaldehyde and 8 mol of ammonia react to produce at most 8 / 3 mol of 1,3,5-hexahydrotriazine. This is a reversible reaction. The reaction formula is as follows:

[0053]

[0054] 2. 3 mol of halogenated hydrocarbons and 8 / 3 mol of 1,3,5-hexahydrotriazine react to generate 2 / 3 mol of 1,3,5-trialkylhexahydrotriazine and 1 mol of N-alkylhexamethylenetetramine quaternary ammonium salt. At this time, 2 mol of inorganic ammonium halide will be produced as a by-product. The reaction formula is as follows:

[0055]

[0056] 3. 2 / 3 mol of 1,3,5-trialkylhexahydrotriazine is hydrolyzed under the action of 4 mol of alcohol and 2 mol of acid to generate 2 mol of ammonium salt of the target product and 2 mol of acetal. The reaction formula is as follows:

[0057]

[0058] 1 mol of N-alkyl hexamethylenetetramine quaternary ammonium salt is hydrolyzed under the action of 12 mol of alcohol and 3 mol of acid to generate 1 mol of the ammonium salt of the target product, 6 mol of acetal and 3 mol of inorganic ammonium salt. The reaction formula is as follows:

[0059]

[0060] 4. The target product ammonium salt is adjusted to strong alkalinity with alkali solution to precipitate the target product primary amine. The reaction formula is as follows:

[0061] RNH2.H + +OH - →RNH2+H2O

[0062] The above is a relatively intuitive and simple explanation used by the inventor to illustrate the principle of the present invention. The actual reaction process may be much more complicated than this. Experimental results confirm that when the ammonia contained in the halogenated hydrocarbon: formaldehyde: ammonia water = 3 mol: 8 mol: 8 mol, the yield of the target product is the highest, and the yield can generally reach more than 80%. If the amount of formaldehyde and ammonia is increased in equal proportion, the effect of improving the yield is not obvious. For example, when the ammonia contained in the halogenated hydrocarbon: formaldehyde: ammonia water = 3 mol: 12 mol: 12 mol, the yield of the primary amine does not change much.

[0063] Since the market prices of formaldehyde and ammonia water are relatively cheaper than halogenated hydrocarbons and ammonia water is easy to volatilize and escape, we slightly increased the dosage of formaldehyde and ammonia water in the experiment, and ensured that the amount of ammonia contained in ammonia water was ≥ the amount of formaldehyde.

[0064] When the dosage of formaldehyde and ammonia is reduced, the target product will also be generated, but the yield will be reduced. For example, when the ammonia contained in the halogenated hydrocarbon: formaldehyde: ammonia water = 1 mol: 1 mol: 2 mol, the experimental yield can also reach more than 60%, but it is not as high as when the ratio of the three is 3:8:8. When the dosage of formaldehyde is reduced, the amount of ammonia can also be reduced, but the reduction in the amount of ammonia should be less than the reduction in the amount of formaldehyde. For example, when the halogenated hydrocarbon: formaldehyde is changed from 3:8 to 1:1, the ammonia contained in the halogenated hydrocarbon: ammonia water should be changed from 3:8 to 1:2.

[0065] The present invention also found that aromatic methyl halides, allylic halogenated hydrocarbons, and partial halogenated compounds with multiple bonds on the carbons connected to the halogenated methyl groups can be applied to the method of the present invention, but the effect on halogenated aliphatic alkanes is not good. Experiments have used tert-butyl chloride and 1-bromooctane as main raw materials, but failed to synthesize the corresponding primary amines.

[0066] Compared with the Delépine reaction, the technical solution of the present invention has the following beneficial effects:

[0067] 1) Less raw material usage, lower carbon, and lower raw material cost of products

[0068] In the Delépine reaction, theoretically, 1 mol of halogenated hydrocarbon and 1 mol of hexamethylenetetramine react to generate 1 mol of quaternary ammonium salt, where 1 mol of hexamethylenetetramine is equivalent to 6 mol of formaldehyde and 4 mol of ammonia. The obtained 1 mol of quaternary ammonium salt is hydrolyzed under the action of 12 mol of alcohol and 3 mol of acid to obtain 1 mol of ammonium salt of the target product, 6 mol of acetal and 3 mol of inorganic ammonium salt. After removing the acetal, it is not economically cost-effective to separate the target product ammonium salt and the inorganic ammonium salt, so the two are often directly adjusted to strong alkalinity with alkali solution without separation, which will consume more than 4 mol of alkali, and then at most 1 mol of the target product primary amine and 3 mol of inorganic ammonia will be precipitated.

[0069] In the present invention, when the ratio of halogenated hydrocarbon: formaldehyde: ammonia contained in ammonia water is 3:8:8, theoretically, after 8 / 3 mol of formaldehyde reacts with 8 / 3 mol of ammonia, it is further reacted with 1 mol of halogenated hydrocarbon to obtain 2 / 9 mol of 1,3,5-trialkylhexahydrotriazine and 1 / 3 mol of N-alkylhexamethylenetetramine quaternary ammonium salt. The two are hydrolyzed under the action of 16 / 3 mol of alcohol and 5 / 3 mol of acid to obtain 1 mol of ammonium salt of the target product, 8 / 3 mol of acetal and 5 / 3 mol of inorganic ammonium salt. After removing the acetal, because it is not economically cost-effective to separate the target product ammonium salt and the inorganic ammonium salt, the two are often directly adjusted to strong alkalinity with alkali solution without separation, and more than 8 / 3 mol of alkali will be consumed at this time, and then at most 1 mol of the target product primary amine and 5 / 3 mol of inorganic ammonia will be precipitated.

[0070] Table 1 lists the minimum amount of raw materials that are theoretically required to produce 1 mol of target product primary amine by the Delépine synthesis method and the present invention.

[0071] Table 1

[0072]

[0073] Obviously, the present invention uses less raw materials, has lower carbon content, and has lower raw material costs for the product.

[0074] (Note: Since methanol in the present invention is used as both a solvent and a reactant, the actual amount used in each batch may appear to be much higher than the theoretical amount. However, in large-scale production applications, the recovered methanol can be reused in the production of the next batch after separation and removal of impurities such as acetal. Such recycling can significantly reduce the actual amount of methanol used.)

[0075] 2) The output of by-products acetal and inorganic ammonia is small, which is more environmentally friendly and greener

[0076] From the above analysis, it can be seen that in the Delépine reaction, theoretically, 6 mol of acetal and 3 mol of inorganic ammonia are produced for every 1 mol of the target product, while the present invention only produces 8 / 3 mol of acetal and 5 / 3 mol of inorganic ammonia for every 1 mol of the target product. Both acetal and inorganic ammonia are compounds with low recovery value, and environmental protection treatment will incur a lot of expenses. Therefore, the synthesis process of the present invention is greener and more environmentally friendly.

[0077] Table 2 lists the amounts of byproduct acetal and ammonia produced by the Delépine synthesis method and the present invention theoretically per 1 mol of the target product primary amine.

[0078] Table 2

[0079]

[0080] 3) The synthesis process is simpler

[0081] The Delépine reaction is equivalent to synthesizing hexamethylenetetramine by reacting formaldehyde and ammonia in a molar ratio of 6:4. Since hexamethylenetetramine has poor solubility in alcohol solvents but good solubility in chloroform, the hexamethylenetetramine can only be dissolved in chloroform and then reacted with halogenated hydrocarbons. After the reaction, the chloroform must be separated and then hydrolyzed into the target product ammonium salt under the action of alcohol solvents such as methanol and acids. The process is complicated and the operation is cumbersome.

[0082] The present invention directly dissolves formaldehyde and ammonia in an alcohol solvent such as methanol at a molar ratio of 1:1 for reaction, then adds halogenated hydrocarbons for sufficient reaction, cools to a suitable temperature after the reaction is completed, and then adds hydrochloric acid and other acidic substances for hydrolysis to form the target product ammonium salt. The reaction is always carried out in the same reactor, the process is simple, and the operation is very easy.

[0083] 4) The yield of the product of the present invention is generally above 80%

[0084] When the feed ratio of the reaction materials is halogenated hydrocarbons: formaldehyde: ammonia contained in ammonia water close to 3:8:8, the yield of the present invention is generally above 80%, and the yield of some products can reach above 85%. This is only the single-pass yield, which is based on the fact that the raw materials such as the extractant and the front and back fractions produced during the vacuum distillation are not recovered and reused. If the raw materials such as the extractant and the front and back fractions produced during the vacuum distillation are recovered and reused, the yield will be higher, and it is very likely to exceed 90%.

[0085] In summary, the invention is highly innovative and has obvious beneficial effects. In the invention, some halogenated hydrocarbons, formaldehyde and ammonia form quaternary ammonium salts of N-alkyl hexamethylenetetramine, and the reaction process is carried out according to the Delépine synthesis method. Therefore, the invention can be regarded as an application and extension of the Delépine synthesis method. BRIEF DESCRIPTION OF THE DRAWINGS

[0086] Figure 1 The gas phase spectrum and content analysis of the product benzylamine in Example 1;

[0087] Figure 2 This is the H NMR spectrum of the product benzylamine in Example 1;

[0088] Figure 3 The gas phase spectrum and content analysis of the product 2-chlorobenzylamine in Example 2;

[0089] Figure 4 This is the H NMR spectrum of the product 2-chlorobenzylamine in Example 2;

[0090] Figure 5 The gas phase spectrum and content analysis of the product 4-fluorobenzylamine in Example 3;

[0091] Figure 6 This is the H NMR spectrum of the product 4-fluorobenzylamine in Example 3;

[0092] Figure 7 The gas phase spectrum and content analysis of the product 4-tert-butylbenzylamine in Example 4;

[0093] Figure 8 The H NMR spectrum and the enlarged benzene ring area spectrum of the product 4-tert-butylbenzylamine in Example 4;

[0094] Fig. 9 The gas phase spectrum and content analysis of the product 2,4-dichlorobenzylamine in Example 5;

[0095] Fig.10 This is the H NMR spectrum of the product 2,4-dichlorobenzylamine in Example 5;

[0096] Fig.11 The gas phase spectrum and content analysis of the product 4-bromobenzylamine in Example 6;

[0097] Fig.12 This is the H NMR spectrum of the product 4-bromobenzylamine in Example 6;

[0098] Fig.13 The gas phase spectrum and content analysis of the product 1-naphthylamine in Example 7;

[0099] Fig.14 This is the H NMR spectrum of the product 1-naphthylmethylamine in Example 7. DETAILED DESCRIPTION

[0100] The present invention is further described below in conjunction with specific embodiments to facilitate a better understanding of the present technical solution.

[0101] Example 1

[0102] Into a 500ml four-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, 33.63g of paraformaldehyde (1.12mol) and 310ml of methanol were added, cooled in an ice-water bath, and 79.77g of 25.62% ammonia water (1.2mol) was added under stirring, and the temperature was controlled below 30°C until the mixture was completely dissolved and clarified, and stirring was continued for 20 minutes, 50.63g of benzyl chloride (0.4mol) was added, the water bath temperature was increased, and the reaction temperature was controlled to be: 58-60°C, and the stirring reaction was stopped after 6 hours, and cooled to room temperature with cold water, and 92g of 36.5% hydrochloric acid (0.92mol) was added. l), heated in a water bath, the reaction temperature was controlled at 44-46°C, after reacting for 2 hours, the reaction was replaced with an atmospheric distillation apparatus, all organic solvents were distilled off, stirred and cooled to room temperature, 58g of pre-cooled sodium hydroxide (1.45mol) and 190ml of water solution were added dropwise, adjusted to strong alkalinity, allowed to stand for stratification, the water layer was extracted with 30ml*3 dichloromethane and then sent to the environmental protection system for waste treatment, the oil layer and the dichloromethane extract were combined, heated to reflux, the water was separated with a water separator, and the dichloromethane was removed by atmospheric distillation, and the dichloromethane was collected by vacuum distillation: 94-95°C / 4.8kPa fraction totaling 34.53g, which was analyzed by gas chromatography (see attached Figure 1 ) detection content: 99.5%, analysis results are shown in Table 3, NMR spectrum (see Appendix Figure 2 ) analysis showed that the target product was benzylamine, and the molar yield of the product (based on benzyl chloride) was 80.2%.

[0103] Table 3

[0104]

[0105] Example 2: Synthesis of 2-chlorobenzylamine from 2-chlorobenzyl chloride

[0106] Into a 500ml four-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, 24.32g of paraformaldehyde (0.81mol) and 300ml of methanol were added, cooled in an ice-water bath, and 74.51g of 19.22% ammonia water (0.84mol) was added under stirring. The temperature was controlled below 30°C until the mixture was completely dissolved and clarified. Stirring was continued for 20 minutes, and 48.3g of 2-chlorobenzyl chloride (0.3mol) was added. The water bath temperature was increased to control the reaction temperature to 58-60°C. The stirring reaction was stopped after 6 hours, cooled to room temperature with cold water, and 71.4ml of 31.0% hydrochloric acid was added. (0.7mol), heated in a water bath, controlled the reaction temperature: 40-45℃, reacted for 2 hours, switched to atmospheric distillation apparatus, distilled off all organic solvents, stopped heating, cooled to room temperature, added dropwise 48.0g of pre-cooled sodium hydroxide (1.2mol) and 72ml of water solution with stirring, adjusted to strong alkalinity, allowed to stand for stratification, the water layer was extracted with 30ml*3 benzene and then sent to the environmental protection system for waste treatment, the oil layer and the benzene extract were combined, heated to reflux and the water was separated with a water separator, the benzene was removed by atmospheric distillation, and the reduced pressure distillation was collected: 84-86℃ / 0.9kPa fraction totaling 34.63g, which was analyzed by gas chromatography (see attached Figure 3 ) detection content: 98.8%, analysis results are shown in Table 4, NMR spectrum (see Appendix Figure 4 ) analysis showed that the target product was 2-chlorobenzylamine, and the molar yield of the product (based on 2-chlorobenzyl chloride) was 80.5%.

[0107] Table 4

[0108]

[0109] Example 3: Synthesis of 4-fluorobenzylamine from 4-fluorobenzyl chloride

[0110] Into a 1000ml four-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, 38.44g of paraformaldehyde (1.28mol) and 400ml of methanol were added, cooled in an ice-water bath, and 88.3g of 27.0% ammonia water (1.4mol) was added under stirring, and the temperature was controlled below 30°C until the mixture was completely dissolved and clarified, and stirring was continued for 30 minutes, 57.83g of 4-fluorobenzyl chloride (0.4mol) was added, the water bath temperature was increased, and the reaction temperature was controlled to be: 55-57°C, the stirring reaction was stopped after 5 hours, cooled to room temperature with cold water, 120.0g of 36.5% hydrochloric acid (1.2mol) was added, and heated in a water bath, and the reaction temperature was controlled to be: 40-4 5℃, after 4 hours of reaction, it was replaced with an atmospheric distillation apparatus to distill off all the organic solvents, stirred for crystallization, cooled to 4℃ with ice water, filtered to dryness, and the crystals obtained by filtration were transferred to a 500ml three-necked flask, 100ml of water was added, and a solution of 76.8g of sodium hydroxide (1.92mol) and 200ml of water that had been cooled in advance was added dropwise under stirring, adjusted to strong alkalinity, allowed to stand for stratification, the water layer was extracted with 30ml*3 dichloromethane and then sent to the environmental protection system for waste treatment, the oil layer and the dichloromethane extract were combined, heated to reflux, and the water was separated with a water separator, and the dichloromethane was removed by atmospheric distillation, and the dichloromethane was removed by vacuum distillation, and the fractions at 63-64℃ / 1.0kPa were 41.53g in total, which were analyzed by gas chromatography (see attached Figure 5 ) detection content: 100%, analysis results are shown in Table 5, NMR spectrum (see Appendix Figure 6 ) analysis showed that the target product was 4-fluorobenzylamine, and the molar yield of the product (based on 4-fluorobenzyl chloride) was 83.0%.

[0111] Table 5

[0112]

[0113] Example 4: Synthesis of 4-tert-butylbenzylamine from 4-tert-butylbenzyl chloride

[0114] Into a 1000ml four-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, 33.63g of paraformaldehyde (1.12mol) and 700ml of methanol were added, cooled in an ice-water bath, and 88.85g of 22.1% ammonia water (1.153mol) was added under stirring, and the temperature was controlled below 30°C until the mixture was completely dissolved and clarified, and stirring was continued for 30 minutes, 63.94g of 4-tert-butylbenzyl chloride (0.35mol) was added, the water bath temperature was increased, and the reaction temperature was controlled to be: 59-61°C, and the stirring reaction was stopped after 7 hours, and cooled to room temperature with cold water, and 74.9ml of 36.5% hydrochloric acid (0.8857mol) was added, and heated in a water bath, and the reaction temperature was controlled to: 39-41°C. After reacting for 3 hours, it was replaced with Atmospheric distillation apparatus, while distilling to remove the organic solvent, add 200ml of water dropwise until all the organic solvent is evaporated, stop heating, cool to room temperature and continue to cool with ice water to below 5°C, stir and crystallize for 3 hours, filter to dryness, transfer the filter cake to a 500ml three-necked flask, add 54.4g of pre-cooled sodium hydroxide (1.36mol) and 200ml of water solution dropwise while stirring, adjust to strong alkalinity, stand and separate, extract the water layer with 50ml*3 methyl tert-butyl ether and then enter the environmental protection system for waste treatment, combine the oil layer and the methyl tert-butyl ether extract, heat reflux and use a water separator to separate the water therein, remove the methyl tert-butyl ether therein by atmospheric distillation, and collect the fraction at 92-94°C / 0.5kPa, a total of 47.19g, which is analyzed by gas chromatography (see attached Figure 7 ) detection content: 100.0%, analysis results are shown in Table 6, NMR spectrum (see Appendix Figure 8 ) analysis showed that the target product was 4-tert-butylbenzylamine, and the molar yield of the product (based on 4-tert-butylbenzyl chloride) was 82.6%.

[0115] Table 6

[0116]

[0117] Example 5: Synthesis of 2,4-dichlorobenzylamine from 2,4-dichlorobenzyl chloride

[0118] Into a 1000ml four-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, add 27.03g of paraformaldehyde (0.9mol) and 450ml of methanol, cool in an ice-water bath, add 74.11g of 21.74% ammonia water (0.9461mol) under stirring, control the temperature below 30°C, until the mixture is completely dissolved and clarified, continue stirring for 60 minutes, add 58.64g of 2,4-dichlorobenzyl chloride (0.3mol), increase the water bath temperature, control the reaction temperature to 59-61°C, stop stirring the reaction after 4 hours, cool to room temperature with cold water, add 78.05g of 36.5% hydrochloric acid (0.7805mol) and 50ml of water, The reaction temperature was controlled at 40-45°C by heating in a water bath. After 4 hours of reaction, the device was replaced with an atmospheric distillation device. While removing the organic solvent by distillation, 300 ml of water was added dropwise until all the organic solvent was evaporated. The device was then stopped heating and cooled to room temperature. A solution of 48.0 g of sodium hydroxide (1.2 mol) and 100 ml of water was added dropwise under stirring. The solution was adjusted to strong alkalinity. The solution was allowed to stand for stratification. The aqueous layer was extracted with 30 ml of 3 dichloromethane and then sent to the environmental protection system for waste treatment. The oil layer and the dichloromethane extract were combined, heated to reflux, and the water was removed by a water separator. The dichloromethane was removed by atmospheric distillation. The distillate was collected by vacuum distillation: a total of 45.77 g of the fraction at 115-117°C / 1.2 kPa was obtained. The fraction was analyzed by gas chromatography (see attached). Fig. 9 ) detection content: 100%, analysis results are shown in Table 7, NMR spectrum (see Appendix Fig.10 ) analysis showed that the target product was 2,4-dichlorobenzylamine, and the molar yield of the product (based on 2,4-dichlorobenzyl chloride) was 86.7%.

[0119] Table 7

[0120]

[0121] Example 6: Synthesis of 4-bromobenzylamine from 4-bromobenzyl bromide

[0122] Into a 1000ml four-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, 25.23g of paraformaldehyde (0.84mol) and 600ml of methanol were added, cooled in an ice-water bath, and 63.69g of 24.12% ammonia water (0.9021mol) was added under stirring, and the temperature was controlled below 30°C until the mixture was completely dissolved and clarified, and stirring was continued for 30 minutes, 74.98g of 4-bromobenzyl bromide (0.3mol) was added, and the water bath temperature was increased to control the reaction temperature to: 54-56°C, and the stirring reaction was stopped after 8 hours, and cooled to room temperature with cold water, and 69.29g of 36.5% hydrochloric acid (0.6929mol) was added, and heated in a water bath to control the reaction temperature to: 44-4 6 ℃, after 2 hours of reaction, change to atmospheric distillation apparatus, while distilling off the organic solvent, add 100 ml of water dropwise, until all the organic solvent is evaporated, stop heating, cool to room temperature, add 44.0 g of sodium hydroxide (1.1 mol) and 100 ml of water solution cooled in advance under stirring, adjust to strong alkalinity, steam distill until the distillate is no longer turbid, let the distilled water stand for stratification, extract the water layer with 40 ml * 3 dichloromethane and then enter the environmental protection system for waste treatment, combine the oil layer and the dichloromethane extract, heat reflux and use a water separator to separate the water, remove the dichloromethane by atmospheric distillation, and collect the fraction of 100-102 ℃ / 0.5 kPa, a total of 48.17 g, by gas chromatography (see attached Fig.11 ) detection content: 99.6%, analysis results are shown in Table 8, NMR spectrum (see Appendix Fig.12 ) analysis showed that the target product was 4-bromobenzylamine, and the molar yield of the product (based on 4-bromobenzyl bromide) was 86.0%.

[0123] Table 8

[0124]

[0125] Example 7: Synthesis of 1-naphthylamine from 1-chloromethylnaphthalene

[0126] Into a 1000ml four-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, add 26.12g of paraformaldehyde (0.87mol) and 600ml of methanol, cool in an ice-water bath, add 65.33g of 24.7% ammonia water (about 0.9475mol) under stirring, control the temperature below 30°C, until the mixture is completely dissolved and clarified, continue stirring for 30 minutes, add 52.99g of 1-chloromethylnaphthalene (0.3mol), increase the water bath temperature, control the reaction temperature to 56-58°C, stop stirring the reaction after 6.5 hours, cool to room temperature with cold water, add 200ml of water and 78.96g of 36.5% hydrochloric acid (0.7896mol), and heat in a water bath. Heat and control the reaction temperature: 40-42°C. After reacting for 3.5 hours, switch to atmospheric distillation apparatus, add 300ml of water dropwise while distilling to remove the organic solvent, until all the organic solvent is evaporated, stop heating, cool to 50°C, add 46.74g of pre-cooled sodium hydroxide (1.169mol) and 100ml of water solution dropwise under stirring, adjust to strong alkalinity, stand and separate, extract the water layer with 30ml*3 dichloromethane and then enter the environmental protection system for waste treatment, combine the oil layer and the dichloromethane extract, heat and reflux, separate the water with a water separator, remove the dichloromethane after atmospheric distillation, and collect the fraction of 154-157°C / 1.5kPa, totaling 39.82g, by gas chromatography (see attached) Fig.13 ) detection content: 98.3%, the analysis results are shown in Table 9, the nuclear magnetic resonance spectrum (see Appendix Fig.14 ) analysis showed that the target product was 1-naphthylmethylamine, and the molar yield of the product (based on 1-chloromethylnaphthalene) was 83.0%.

[0127] Table 9

[0128]

[0129] Due to space limitations, the present invention will no longer cite too many embodiments in detail, such as: 2-methylbenzyl chloride synthesizes 2-methylbenzylamine, 4-methylbenzyl chloride synthesizes 4-methylbenzylamine, 4-chlorobenzyl chloride synthesizes 4-chlorobenzylamine, 2-bromobenzyl bromide synthesizes 2-bromobenzylamine, 2-fluorobenzyl chloride synthesizes 2-fluorobenzylamine, 3,4-dichlorobenzyl chloride synthesizes 3,4-dichlorobenzylamine, 2,4-difluorobenzyl chloride synthesizes 2,4-difluorobenzylamine, 2,4-difluorobenzyl bromide synthesizes 2,4-difluorobenzylamine, (trifluoromethyl)benzyl chloride synthesizes (trifluoromethyl)benzylamine, diphenylmethane synthesizes diphenylmethane, 4 4-[2-(dimethylamino)ethoxy]benzylamine synthesized from 4-[2-(dimethylamino)ethoxy]benzyl chloride, 4-[2-(dimethylamino)ethoxy]benzyl bromide synthesized from 4-[2-(dimethylamino)ethoxy]benzylamine, 2-chloromethylnaphthalene synthesized from 2-naphthylmethylamine, 2-chloro-5-chloromethylthiazole synthesized from 2-chloro-5-chloromethylthiazole, 2-chloro-5-aminomethylthiazole synthesized from 2-chloro-5-chloromethylpyridine, pyridinemethylamine synthesized from chloromethylpyridine, methoxybenzyl chloride synthesized from methoxybenzylamine, thiophenemethylamine synthesized from chloromethylthiophene, etc. All the methods of the present invention or only slightly modified methods of the present invention used as raw materials to synthesize the corresponding primary amines should fall within the scope of protection of the present invention.

Claims

1. A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials, characterized in that The method comprises the following steps: 1) Place formaldehyde or paraformaldehyde and a sufficient amount of alcohol solvent into a four-necked flask equipped with a stirrer, a thermometer, a reflux condenser, and a dropping funnel, add ammonia water dropwise while cooling in an ice-water bath and stirring, control the temperature at 0°C to reflux temperature until the mixture is completely dissolved and continue stirring for 0 to 2 hours; 2) Add a halogenated hydrocarbon dropwise into a four-necked flask, stir and heat in a water bath, and fully react for 0.5 to 24 hours at 20°C to reflux temperature, wherein the halogenated hydrocarbon is an aromatic methyl halide; 3) After the reaction is completed, cool slightly, control the temperature at 0-60°C, stir and dropwise add 0.9A-1.5A equivalent of inorganic acid or organic acid, where A refers to: the amount of ammonia contained in ammonia water - the amount of halogenated hydrocarbon, add a small amount of water if necessary, stir and react at 0-60°C for 0.5-10 hours; 4) removing the reflux condenser and replacing it with a distillation device, adding an appropriate amount of water when necessary, and stopping after all the organic solvents are evaporated, and then post-processing to obtain the finished primary amine; the primary amine is an aromatic methyl amine; The molar ratio of each reactant is 1.0:2.6-3.2:2.6-3.5 of halogenated hydrocarbon:formaldehyde:ammonia contained in ammonia water, and the amount of ammonia contained in ammonia water is ≧the amount of formaldehyde.

2. A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials as claimed in claim 1, characterized in that: The molar ratio of the reactants is 3:8:8 for halogenated hydrocarbon: formaldehyde: ammonia contained in aqueous ammonia.

3. A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials as claimed in claim 1, characterized in that In step 1), the temperature is controlled at 15 to 30° C.; the alcohol solvent is selected from methanol or ethanol, and the stirring time after dissolution is continued for 20 to 60 minutes.

4. A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials as claimed in claim 1, characterized in that The amount of alcohol added is sufficient to ensure that the reaction mixture is in a solution state after the halogenated hydrocarbon is added dropwise in the subsequent step 2). The actual amount used varies depending on the halogenated hydrocarbon and is greater than twice the amount of formaldehyde.

5. A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials as claimed in claim 1, characterized in that In step 2), after the halogenated hydrocarbon is added dropwise, the temperature of the water bath is heated to 30-65° C.; the sufficient reaction time is 1-12 hours.

6. A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials as claimed in claim 1, characterized in that In step 3), the appropriate temperature is controlled to be 20-50°C, the amount of acid added is 1.0A-1.3A equivalent acid, where A refers to: the amount of ammonia contained in ammonia water - the amount of halogenated hydrocarbon substance, the acid is hydrochloric acid, and the stirring reaction time is 1-5 hours.

7. A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials as claimed in claim 1, characterized in that In step 4), the distillation device adopts atmospheric distillation or reduced pressure distillation; the appropriate amount of water means that the amount of water added is sufficient to dissolve the ammonium chloride precipitated in the later stage of distillation, so that all the organic solvent can be distilled out normally.

8. A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials as claimed in claim 1, characterized in that In step 4), post-processing adopts the following different methods, specifically: Method A: After the distillation residue is cooled slightly, it is adjusted to strong alkalinity with an aqueous solution of 0.9B to 1.5B equivalent of alkali metal or alkaline earth metal hydroxide, and the stratification is allowed to stand. The water layer is extracted with a suitable extractant and then enters an environmental protection treatment system. The extract and the oil layer are combined, and the water is removed and then vacuum distilled. The appropriate fraction is collected to obtain the finished primary amine; Method B: Cool the distillation residue with ice water to crystallize, vacuum filter to dryness, adjust the obtained crystals to strong alkalinity with 0.9B to 1.5B equivalent of alkali metal or alkaline earth metal hydroxide aqueous solution, let stand to separate, extract the water layer with a suitable extractant and then enter the environmental protection treatment system, combine the extract and the oil layer, remove the water and then conduct vacuum distillation, collect the suitable fraction to obtain the finished primary amine; Method C: The distillation residue is adjusted to a strong alkalinity by method A or method B, and then subjected to steam distillation. The distillate is allowed to stand for stratification, the water layer is extracted with a suitable extractant and then enters an environmental treatment system, the extract and the oil layer are combined, the water is removed, and then vacuum distillation is performed, and the appropriate fractions are collected to obtain the finished primary amine; In the above methods, B refers to: the amount of the acid substance added + the amount of the halogenated hydrocarbon substance; the extractant is an ether substance or a homologue of benzene or a partially halogenated hydrocarbon.

9. A low-carbon and environmentally friendly method for synthesizing primary amines using halogenated hydrocarbons as raw materials as claimed in claim 8, characterized in that The aqueous solution of alkali metal or alkaline earth metal hydroxide is sodium hydroxide aqueous solution or potassium hydroxide aqueous solution; the usage amount is 1.0B to 1.3B, wherein B refers to: the amount of the acid substance added + the amount of the halogenated hydrocarbon substance; The ether substance can be selected from any one of ethyl ether, propyl ether, isopropyl ether, butyl ether, methyl tert-butyl ether and anisole; the benzene homologue can be selected from any one of benzene, toluene and xylene; the partial halogenated hydrocarbon can be selected from dichloromethane; The method for removing moisture is: drying with inorganic salt and filtering to remove moisture, wherein the inorganic salt is selected from any one of anhydrous potassium carbonate, anhydrous sodium carbonate, and anhydrous sodium sulfate; or utilizing the characteristic that the extractant and water can form an azeotropic mixture, heating reflux and separating the moisture therein with a water separator.

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