Catalytic system for preparing amine compounds through nitro reduction and application of catalytic system

Abstract

The invention discloses a catalytic system for preparing amine compounds through nitro reduction and application of the catalytic system. The catalytic system comprises an alkaline aqueous solution, a reducing agent and a catalyst, the alkaline aqueous solution is an alkali metal hydroxide aqueous solution; the reducing agent is alkali metal hydroboron and / or alkaline earth metal hydroboron; the catalyst is copper salt lewis acid and / or other lewis acid; the other Lewis acid is selected from one or a combination of more of cobalt salt, ferric salt, zinc salt, manganese salt and palladium salt. When the catalytic system is used for reducing the aromatic nitro-compound, the using amount of a reducing agent is small, meanwhile, the using amount of an organic solvent is reduced, the reaction yield is high, the reaction is milder, and amplified production of the process is facilitated.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis intermediate preparation, and particularly relates to a catalytic system for preparing amine compounds by nitro reduction and application thereof. BACKGROUND

[0002] Aromatic amine compounds are important organic synthesis intermediates, which can be used for synthesizing dyes, drugs, additives and textile auxiliaries, etc., and are mainly obtained by reducing aromatic nitro compounds. This method is to realize the reduction of nitro compounds to prepare amine compounds by using a reducing agent under the action of a catalyst. Although researchers have developed various reduction systems, sodium borohydride system is still widely used in actual industrial production. Under the action of a catalyst, sodium borohydride can realize the reduction of nitro compounds to prepare aromatic amines at normal temperature and pressure. However, there are still some problems in this system: (1) excessive reducing agent problem - in order to make the reaction complete, sodium borohydride (≥100 equivalents) is used in excess of stoichiometry, which increases the production cost and causes the risk of uncontrolled heat release, which is not conducive to the safety production of industrialization; (2) unsustainable catalyst - noble metal catalysts are not only expensive, but also have the problems of noble metal loss and stability.

[0003] In order to solve the problems existing in the prior art, Mario Ficker et al. (Hydrogenation of Aromatic Nitro Compounds with an Inexpensive and Efficient CuSO4 / CoCl2Catalyst Prepared in situ using NaBH4 as the Hydrogen Source) reported in 2014 that aromatic nitro compounds were reduced to aromatic amine compounds in a mixture of methanol and toluene as solvent, using copper sulfate / cobalt chloride as catalyst, and adding 3-6 molar equivalents of sodium borohydride as reducing agent, using a combination of copper-cobalt catalytic system to realize in-situ reduction of sodium borohydride, but the reaction condition uses an organic solvent system, which does not meet the requirements of green chemistry, and the sodium borohydride is excessive, which still has the problems of high raw material cost and the risk of violent reaction heat release, which is not conducive to the scale-up production of the process. SUMMARY

[0004] The present application provides a catalytic system for reducing aromatic nitro compounds to prepare aromatic amine compounds and application thereof. When the catalytic system is used for the reduction of aromatic nitro compounds, the amount of reducing agent is small, the use of organic solvent is reduced, the yield of the reaction is high, the reaction is more mild, and it is conducive to the scale-up production of the process.

[0005] The technical scheme of the present application is as follows:

[0006] A catalytic system for preparing amine compounds by nitro reduction, comprising an alkaline aqueous solution, a reducing agent and a catalyst;

[0007] The alkaline aqueous solution is an aqueous solution of an alkali metal hydroxide;

[0008] The reducing agent is an alkali metal borohydride and / or an alkaline earth metal borohydride;

[0009] The catalyst is a copper salt Lewis acid and / or other Lewis acid except the copper salt Lewis acid;

[0010] The other Lewis acid is selected from a combination of one or more of a cobalt salt, an iron salt, a zinc salt, a manganese salt and a palladium salt.

[0011] When the catalytic system of the present application is used for preparing amine compounds by nitro reduction, the addition of the catalyst improves the activity of the reducing agent, so that the reducing agent can realize the reduction of nitro groups; at the same time, by introducing the alkali metal hydroxide, the hydrolysis of the alkali metal borohydride / alkaline earth metal borohydride itself is inhibited, and the amount of the reducing agent is reduced.

[0012] As a preference, the alkali metal hydroxide is selected from a combination of one or more of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide and cesium hydroxide; the concentration of the aqueous solution of the alkali metal hydroxide is 8-15 wt%.

[0013] As a preference, the alkali metal borohydride is selected from a combination of one or more of lithium borohydride, sodium borohydride and potassium borohydride; the alkaline earth metal borohydride is selected from a combination of one or both of magnesium borohydride and calcium borohydride;

[0014] As a preference, the copper salt Lewis acid is a monovalent copper salt and / or a divalent copper salt, and the acid radical of the copper salt Lewis acid is selected from a combination of one or more of chloride ion, bromide ion, sulfate ion, acetate ion, nitrate ion and trifluoroacetate ion.

[0015] Further, the copper salt Lewis acid is selected from a combination of one or more of copper chloride, cuprous chloride, copper acetate, copper sulfate and cuprous sulfate.

[0016] The other Lewis acid is a combination of one or more of cobalt chloride, cobalt acetate, iron chloride, zinc chloride, zinc bromide, zinc acetate, manganese chloride, manganese acetate and palladium trifluoroacetate.

[0017] The present application also provides an application of the catalytic system as described above in the preparation of aromatic amine compounds by reduction of aromatic nitro compounds, comprising the following steps:

[0018] Step S1: adding an aromatic nitro compound, the catalyst to the aqueous alkali metal hydroxide solution, heating the reaction system to 40-60°C to form a reaction substrate containing the catalyst;

[0019] Step S2: adding the reducing agent to the reaction substrate containing the catalyst formed in step S1 in a batch manner to make the aromatic nitro compound undergo a reduction reaction, controlling the reaction temperature to be 75-100°C, and obtaining a reaction liquid containing an aromatic amine compound after the reaction is completed;

[0020] Step S3: obtaining the aromatic amine compound product from the reaction liquid containing the aromatic amine compound obtained in step S2 after treatment.

[0021] In step S1, the concentration of the aqueous alkali metal hydroxide solution is 8-15wt%; the alkali metal borohydride is selected from one or more combinations of lithium borohydride, sodium borohydride, and potassium borohydride; and the alkaline earth metal borohydride is selected from one or more combinations of magnesium borohydride and calcium borohydride.

[0022] In step S1, the aromatic nitro compound is represented by formula 1:

[0023]

[0024] In formula 1, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 each independently represent a nitro group, hydrogen, deuterium, a halogen, a cyano group, a p-toluenesulfonyl group, a substituted or unsubstituted (C1-C 12 )alkyl group, a substituted or unsubstituted (C3-C 12 )cycloalkyl group, a substituted or unsubstituted (C1-C 12 )alkoxy group, a substituted or unsubstituted (C6-C 30 )aryl group, a substituted or unsubstituted (3- to 12-membered)heteroaryl group, and at least one of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is a nitro group, and at most three are nitro groups simultaneously; preferably a nitro group, hydrogen, deuterium, a substituted or unsubstituted (C1-C 12 )alkyl group, a substituted or unsubstituted (C1-C 12 )alkoxy group, and further preferably a nitro group, hydrogen, deuterium, a methyl group, an ethyl group, a methoxy group, or an ethoxy group;

[0025] The (C1-C 12)alkyl, (C3-C 12 )alkyl, (C3-C 12 )alkyl, (C3-C

[0026] said (C6-C 30 )aryl or (3- to 12-membered)heteroaryl is substituted with one or more of C1-C4alkyl, C1-C4alkoxy, halogen, hydroxyl, p-toluenesulfonyl, or trifluoromethyl;

[0027] wherein when R 1 , R 2 , R 3 , R 4 , R 5 and R 6 contain two nitro groups, the two nitro groups are in ortho position (i.e. R 1 , R 2 are nitro groups, R 3 , R 4 , R 5 and R 6 are independently selected from the above substituents except nitro groups), meta position (i.e. R 1 , R 3 are nitro groups), para position (i.e. R 1 , R 4 are nitro groups); when R 1 , R 2 , R 3 , R 4 , R 5 and R 6 contain three nitro groups, the three nitro groups are in meta position (i.e. R 1 , R 3 , R 5 are nitro groups).

[0028] In step S1, the catalyst is a copper salt Lewis acid and / or another Lewis acid other than the copper salt Lewis acid; the copper salt Lewis acid is a monovalent copper salt and / or a divalent copper salt, the acid radical of the copper salt Lewis acid is selected from the group consisting of one or more of chloride, bromide, sulfate, acetate, triflate;

[0029] the other Lewis acid other than the copper salt Lewis acid is selected from the group consisting of one or more of cobalt salt, iron salt, zinc salt, manganese salt, palladium salt;

[0030] the copper salt Lewis acid is selected from the group consisting of one or more of copper chloride, copper(I) chloride, copper acetate, copper sulfate, copper(I) sulfate;

[0031] The Lewis acid other than the copper salt Lewis acid is a combination of one or more selected from cobalt chloride, cobalt acetate, iron chloride, zinc chloride, zinc bromide, zinc acetate, manganese chloride, manganese acetate, and palladium trifluoroacetate;

[0032] In step S1, the molar ratio of the aromatic nitro compound: alkali metal hydroxide: catalyst is 1:(2.0-2.5):(0.04-0.08).

[0033] In step S1, a low-carbon alcohol organic solvent can also be added at the same time, and the low-carbon alcohol organic solvent is selected from C1-C5 alkyl alcohol, preferably methanol, ethanol, isopropanol, and tert-butanol.

[0034] In step S1, the mass-volume ratio of the aromatic nitro compound: low-carbon alcohol organic solvent is 1:(0.1-0.5) kg / L; although the catalytic system of the present application also adds a low-carbon alcohol organic solvent, the amount is smaller than that of the prior art, which can effectively reduce the safety hazard, and a small amount of low-carbon alcohol organic solvent can increase the solubility of the aromatic nitro compound, which is beneficial to the reaction.

[0035] In step S2, the reducing agent is a combination of one or more of alkali metal borohydride and / or alkaline earth metal borohydride; the alkali metal borohydride is selected from a combination of one or more of lithium borohydride, sodium borohydride, and potassium borohydride; and the alkaline earth metal borohydride is selected from a combination of one or both of magnesium borohydride and calcium borohydride.

[0036] In step S2, the molar ratio of the aromatic nitro compound: reducing agent is 1:(2.0-2.5).

[0037] In step S2, the feeding number of the batch feeding is 5-30 times, the feeding reaction temperature is controlled at 75-80℃, the time interval of each batch feeding is 5-60 min, and after the feeding is completed, the stirring reaction is continued for 2-5 h.

[0038] In step S3, the post-treatment includes: after the reaction is completed, the temperature is lowered, the mixture is left to stand, the phases are separated, the organic phase is filtered, extracted, concentrated, then 2wt%-8wt% potassium hydroxide and / or sodium hydroxide are added, mixed, and then the aromatic amine compound is obtained by rectification.

[0039] The catalytic system of the present application is particularly suitable for deuterium-containing aromatic nitro compounds, and as a preferred, at least one of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 in the aromatic nitro compound is deuterium, and after the reduction reaction, the degree of deuteration can be more effectively maintained.

[0040] In addition, the catalytic system of the present application is suitable for industrial production, and has more advantages compared with the prior art when the amount of raw materials is large. Preferably, the amount of the aromatic nitro compound is in the kg level, more preferably 1-100 kg, and further more preferably 10-100 kg.

[0041] Compared with the prior art, the present application has the following advantages:

[0042] (1) A new aromatic nitro reduction catalytic system is used, which has strong reduction capacity for nitro groups but little effect on other common functional groups (such as carbonyl, cyano, halogen, etc.), can selectively reduce nitro groups to amino groups in multi-functional compounds, and has less by-products. In addition, the catalytic system introduces alkali metal hydroxide, which inhibits the hydrolysis of alkali metal borohydride / alkaline earth metal borohydride itself, and reduces the amount of reducing agent.

[0043] (2) Water is used as the reaction solvent, avoiding the use of toxic or flammable organic solvents. After the reaction, simple liquid separation and filtration can obtain the crude product, which is safe and economical, simple to handle, and in line with the concept of green chemistry.

[0044] (3) The alkali metal borohydride / alkaline earth metal borohydride is added in batches, which can gradually release the reaction heat, avoid the reaction from proceeding too quickly, the sudden rise in system temperature, and the problems of catalyst decomposition and excessive reduction of by-products. Through kinetic control, the safety, selectivity and efficiency of the reaction are maximized.

[0045] (4) The addition of potassium hydroxide and / or sodium hydroxide through rectification can make the aromatic amine compounds more stable in complex systems at high temperatures. In addition, potassium hydroxide and / or sodium hydroxide can achieve the effect of water removal, impurity removal and decolorization. DETAILED DESCRIPTION

[0046] Example 1:

[0047]

[0048] Step S1: 560 mL of water and 62.3 g of sodium hydroxide were added to a 1 L kettle and stirred to dissolve until clear, forming a 10 wt% sodium hydroxide aqueous solution. Then, 100 g (0.78 mol) of deuterated nitrobenzene (deuterium enrichment 99.58%) and 6.30 g (0.047 mol) of copper dichloride were added to the sodium hydroxide aqueous solution, and the temperature was raised to 60°C;

[0049] Step S2: 59.04 g (1.56 mol) of sodium borohydride was added in batches (a total of 5 times, 7.5 g each time for the first two times, with an interval of 5 minutes for each addition; 15 g each time for the subsequent times, with an interval of 10 minutes for each addition; 14.04 g for the last time), and the reaction temperature was controlled at 75°C during the entire addition process. After the addition was completed, the reaction temperature was maintained at 75°C, and the reaction was continuously stirred for 3 hours. After sampling and GC detection, there was no raw material residue, and the intermediate was less than 0.2%, indicating that the reaction was completed;

[0050] Step S3: The reaction solution of step S2 was cooled to room temperature, and after standing and phase separation, the upper organic phase was filtered, then 30 mL of ethyl acetate was added for extraction, and saturated brine was washed once. The solvent was rotary evaporated to obtain 112 g of crude deuterated aniline (containing ethyl acetate); then 5.60 g of potassium hydroxide was added to the obtained crude deuterated aniline for rectification, and 73.01 g of fine deuterated aniline was obtained, with a molar yield of 95.3%, a deuterium substitution degree of 99.56%, and a purity of >99%.

[0051] Example 2:

[0052]

[0053] Step S1: 5.6 L of water and 6.23 kg of sodium hydroxide were added to a 100 L kettle and stirred to dissolve until clear, forming a 10 wt% sodium hydroxide aqueous solution; then 10 kg (72.9 mol) of o-nitrotoluene, 490 g (3.65 mol) of copper dichloride were added to the sodium hydroxide aqueous solution, and the temperature was raised to 60°C;

[0054] Step S2: 5517.0 g (145.82 mol) of sodium borohydride was added in batches (a total of 25 times, 180 g each time for the first 10 times, with an interval of 30 minutes for each addition; 250 g each time for the subsequent times, with an interval of 60 minutes for each addition; 217 g for the last time), and the reaction temperature was controlled at 75°C during the entire addition process. After the addition was completed, the reaction temperature was maintained at 75°C, and the reaction was continuously stirred for 3 hours. After sampling and GC detection, there was no raw material residue, and the intermediate was less than 0.2%, indicating that the reaction was completed;

[0055] Step S3: The reaction solution of step S2 was cooled to room temperature, and after standing and phase separation, the upper organic phase was filtered, then 30 mL of ethyl acetate was added for extraction, and saturated brine was washed once. The solvent was rotary evaporated to obtain 112 g of crude deuterated aniline (containing ethyl acetate); then 5.60 g of potassium hydroxide was added to the obtained crude deuterated aniline for rectification, and 73.01 g of fine deuterated aniline was obtained, with a molar yield of 95.3%, a deuterium substitution degree of 99.56%, and a purity of >99%.

[0056] Example 3:

[0057]

[0058] Step S1 : 5.6 L water and 4.87 kg sodium hydroxide were added into a 100 L kettle and stirred to dissolve to form an 8 wt% sodium hydroxide aqueous solution; then 10 kg (54.91 mol) 2,6-dinitrotoluene, 526 g (3.29 mol) copper sulfate were added into the sodium hydroxide aqueous solution, and the temperature was raised to 60°C;

[0059] Step S2: 2744.28 g (126 mol) sodium borohydride was added in batches (a total of 20 times, the first 6 times each added 100 g, each time the feeding interval was 20 minutes; the subsequent each added 150 g, each time the feeding interval was 40 minutes; the last time added 194.28 g), and the reaction temperature was controlled at 75°C during the whole feeding process. After the feeding was completed, the reaction temperature was maintained at 75°C and the stirring reaction was continued for 3 hours. After sampling and GC detection, there was no raw material residue, and the intermediate was less than 0.2%, and the reaction was completed;

[0060] Step S3: The reaction solution of step S2 was reduced to room temperature, and the upper organic phase was separated after standing and phase separation. Then 12 L ethyl acetate was added for extraction, and saturated brine was washed once. The solvent was rotary evaporated to obtain 2,6-diaminotoluene crude product 10.2 kg (containing ethyl acetate); then 0.612 kg potassium hydroxide was added to the obtained 2,6-diaminotoluene crude product for rectification to obtain 2,6-diaminotoluene fine product 6.47 kg, with a molar yield of 96.5% and a purity of >99%.

[0061] Example 4:

[0062]

[0063] Step S1 : 560 mL water and 76.4 g potassium hydroxide were added into a 1 L kettle and stirred to dissolve to form a 12 wt% potassium hydroxide aqueous solution; then 100 g (0.59 mol) p-dinitrobenzene-d4 (deuterium substitution degree 99.50%) was added into the potassium hydroxide aqueous solution, 2.83 g (0.029 mol) cuprous chloride, 0.93 g (0.007 mol) cobalt chloride, and the temperature was raised to 60°C;

[0064] Step S2: 45.01 g (1.19 mol) sodium borohydride was added in batches (a total of 4 times, the first 2 times each added 7.5 g, each time the feeding interval was 5 minutes; the third time added 15 g, after 10 minutes, the last time added 15.01 g), and the reaction temperature was controlled at 75°C during the whole feeding process. After the feeding was completed, the reaction temperature was maintained at 75°C and the stirring reaction was continued for 3 hours. After sampling and GC detection, there was no raw material residue, and the intermediate was less than 0.2%, and the reaction was completed;

[0065] Step S3: The reaction solution of step S2 was cooled to room temperature, and then allowed to stand and separate into two phases. The upper organic phase was filtered, and then extracted with 30 mL of ethyl acetate. The resulting mixture was washed with saturated brine once, and then the solvent was removed by rotary evaporation to obtain 105 g of crude p-phenylenediamine-d4 (containing ethyl acetate). Then, 5.25 g of potassium hydroxide was added to the obtained crude p-phenylenediamine-d4 for rectification to obtain 63.17 g of fine p-phenylenediamine-d4, with a molar yield of 94.7%, a deuterium enrichment of 99.48%, and a purity of >99%.

[0066] Example 5

[0067]

[0068] Step S1: 5.60 L of water and 6.23 kg of sodium hydroxide were added to a 200 L kettle, and stirred to form a 10 wt% sodium hydroxide aqueous solution. Then, 10 kg (6.53 mol) of 2-nitroanisole, 0.527 kg (3.92 mol) of copper dichloride, and 3 L of ethanol were added to the sodium hydroxide aqueous solution, and the temperature was raised to 60°C.

[0069] Step S2: 4940.58 g (130.6 mol) of sodium borohydride was added in batches (a total of 27 times, 150 g each time for the first 10 times, with an interval of 30 minutes for each addition; 200 g each time for the subsequent additions, with an interval of 60 minutes for each addition; and 240.58 g for the last addition). The reaction temperature was controlled at 75°C during the entire feeding process. After the feeding was completed, the reaction was continued to stir at 75°C for 3 hours. Then, the reaction was sampled and detected by GC. The results showed that there was no raw material residue, and the intermediate was less than 0.2%. The reaction was completed.

[0070] Step S3: The reaction solution of step S2 was cooled to room temperature, and then allowed to stand and separate into two phases. The upper organic phase was filtered, and then extracted with 30 mL of ethyl acetate. The resulting mixture was washed with saturated brine once, and then the solvent was removed by rotary evaporation to obtain 105 g of crude p-phenylenediamine-d4 (containing ethyl acetate). Then, 5.25 g of potassium hydroxide was added to the obtained crude p-phenylenediamine-d4 for rectification to obtain 63.17 g of fine p-phenylenediamine-d4, with a molar yield of 94.7%, a deuterium enrichment of 99.48%, and a purity of >99%.

[0071] Example 6

[0072]

[0073] Step S1: 5.60 L of water and 6.23 kg of sodium hydroxide were added to a 200 L kettle, and stirred to form a 10 wt% sodium hydroxide aqueous solution. Then, 10 kg (6.53 mol) of 2-nitroanisole, 0.527 kg (3.92 mol) of copper dichloride, and 3 L of ethanol were added to the sodium hydroxide aqueous solution, and the temperature was raised to 60°C.

[0074] Step S2: 5108 g (135.03 mol) of sodium borohydride was added in batches (total of 28 times, the first 12 times each added 160 g, each feeding interval 30 minutes; the subsequent each added 200 g, each feeding interval 60 minutes; the last time added 188 g), the whole feeding process controlled the reaction temperature at 75°C. After the feeding was completed, the reaction temperature was kept at 75°C and the reaction was continuously stirred for 3 hours. After sampling and GC detection, there was no raw material residue in the reaction, and the intermediate was less than 0.2%. The reaction was completed;

[0075] Step S3: The reaction solution of step S2 was cooled to room temperature, and the upper organic phase was filtered after phase separation, then 12 L of ethyl acetate was added for extraction, and saturated brine was washed once. The solvent was rotary evaporated to obtain 11.6 kg of crude p-aminobenzonitrile (containing ethyl acetate); Step S5: 0.58 kg of potassium hydroxide was added to the crude p-aminobenzonitrile obtained in step S4 for rectification, and 7.64 kg of p-aminobenzonitrile was obtained, with a molar yield of 95.8% and a purity of >99%.

[0076] Example 7:

[0077]

[0078] Step S1: 5.6 L of water and 9.88 kg of potassium hydroxide were added to a 200 L kettle and stirred to dissolve until the solution was clear, forming a 15 wt% potassium hydroxide aqueous solution; then 10 kg (40.95 mol) of 1,3-dinitro-5-phenylbenzene, 223.26 g (1.64 mol) of zinc chloride, 544.55 g (1.64 mol) of palladium trifluoroacetate, 5 L of isopropyl alcohol were added to the potassium hydroxide aqueous solution, and the temperature was raised to 60°C;

[0079] Step S2: 5522.11 g (102.38 mol) of potassium borohydride was added in batches (total of 30 times, the first 12 times each added 160 g, each feeding interval 40 minutes; the subsequent each added 200, each feeding interval 60 minutes; the last time added 202.11 g), the whole feeding process controlled the reaction temperature at 75°C. After the feeding was completed, the reaction temperature was kept at 75°C and the reaction was continuously stirred for 3 hours. After sampling and GC detection, there was no raw material residue in the reaction, and the intermediate was less than 0.2%. The reaction was completed;

[0080] Step S3: The reaction solution of step S2 was cooled to room temperature, and then allowed to stand and separate into two phases. The upper organic phase was filtered, and then extracted with 12 L of ethyl acetate. The organic phase was washed with saturated brine once, and then the solvent was removed by rotary evaporation to obtain 1,1'-biphenyl-3,5-diamine crude product 11.1 kg (containing ethyl acetate). Then, 0.89 kg of potassium hydroxide was added to the obtained 1,1'-biphenyl-3,5-diamine crude product for rectification to obtain 1,1'-biphenyl-3,5-diamine fine product 7.14 kg, with a molar yield of 94.7% and a purity of >99%.

[0081] Example 8:

[0082]

[0083] Step S1: 56 L of water and 6.23 kg of sodium hydroxide were added to a 100 L kettle and stirred to form a 10 wt% sodium hydroxide aqueous solution. Then, 8000 g (62.43 mol) of deuterated nitrobenzene (deuterium enrichment 99.65%) and 503.64 g (3.746 mol) of copper chloride were added to the sodium hydroxide aqueous solution, and the temperature was raised to 60°C.

[0084] Step S2: 4959 g (130.09 mol) of sodium borohydride was added in batches (total of 25 times, the first 10 times each added 120 g (3.172 mol), with an interval of 30 minutes for each addition; the subsequent each added 250 g (6.609 mol), with an interval of 60 minutes for each addition; the last time added 259 g, and the whole feeding process was controlled at a reaction temperature of 75°C. After the feeding was completed, the reaction temperature was maintained at 75°C for 3 hours of continuous stirring, and then a sample was taken for GC detection. The GC apparent content of the product was 99.75%, there was no raw material residue, and the intermediate was less than 0.2%. The reaction was completed.

[0085] Step S3: The reaction solution of step S2 was cooled to room temperature, and then allowed to stand and separate into two phases. The upper organic phase was filtered, and then extracted with 12 L of ethyl acetate. The organic phase was washed with saturated brine once, and then the solvent was removed by rotary evaporation to obtain 1,1'-biphenyl-3,5-diamine crude product 11.1 kg (containing ethyl acetate). Then, 0.89 kg of potassium hydroxide was added to the obtained 1,1'-biphenyl-3,5-diamine crude product for rectification to obtain 1,1'-biphenyl-3,5-diamine fine product 7.14 kg, with a molar yield of 94.7% and a purity of >99%.

[0086] Comparative Example 1 differs from Example 1 in that no sodium hydroxide was added in step S1.

[0087] Comparative Example 2 differs from Example 1 in that no sodium hydroxide was added in step S1, and water was replaced by methanol.

[0088] Comparative Example 3 differs from Example 1 in that the concentration of the sodium hydroxide aqueous solution in step S1 was 2 wt%.

[0089] Comparative Example 4 differs from Example 1 in that no potassium hydroxide is added during the distillation of the crude deuterated aniline in step S3.

[0090] Comparative Example 5 differs from Example 2 in that no sodium hydroxide is added in step S1.

[0091] The reaction data of Comparative Examples 1 to 4 are summarized in Table 1:

[0092] Table 1

[0093] No. Molar yield / % Deuterium enrichment / % Purity / % Comparative Example 1 83.6％ 99.42％ ＞99％ Comparative Example 2 92.8％ 99.50％ ＞99％ Comparative Example 3 87.2％ 99.38％ ＞99％ Comparative Example 4 94.7％ 94.37％ ＞99％ Comparative Example 5 85.2％ / ＞99％

[0094] According to Table 1, in Comparative Example 1, no sodium hydroxide is added, resulting in hydrolysis loss of the reducing agent sodium borohydride, incomplete reaction of the raw material, and reduced reaction yield. In Comparative Example 2, methanol is used instead of water as the reaction solvent, although there is no significant reduction in yield, deuterium substitution degree, and purity, but because the boiling point of methanol is lower than that of water, the evaporation of the solvent during the reaction process poses a safety hazard, and is not suitable for industrial production. In Comparative Example 3, the amount of sodium hydroxide added is insufficient, which fails to completely inhibit the hydrolysis of sodium borohydride, resulting in partial loss of the reducing agent and reduced reaction yield. In Comparative Example 4, no sodium hydroxide is added during the distillation process, which causes the deuterium to be lost in the deuterated aniline under high-temperature distillation conditions, resulting in a reduced deuterium substitution degree of the product. In Comparative Example 5, the scale-up reaction of the non-deuterium system without the addition of sodium hydroxide results in hydrolysis loss of the reducing agent sodium borohydride, incomplete reaction of the raw material, and reduced reaction yield.

Claims

1. A catalytic system for the reduction of nitro compounds to prepare amine compounds, characterized in that, Includes alkaline aqueous solutions, reducing agents, and catalysts; The alkaline aqueous solution is an aqueous solution of an alkali metal hydroxide; The reducing agent is an alkali metal borohydride and / or an alkaline earth metal borohydride; The catalyst is a copper salt Lewis acid and / or other Lewis acids; The other Lewis acids are selected from one or more combinations of cobalt salts, iron salts, zinc salts, manganese salts, and palladium salts.

2. The catalytic system for the nitro reduction preparation of amine compounds according to claim 1, characterized in that, The alkali metal hydroxide is selected from one or more combinations of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, and cesium hydroxide; The concentration of the alkali metal hydroxide aqueous solution is 8–15 wt%.

3. The catalytic system for the nitro reduction preparation of amine compounds according to claim 1, characterized in that, The alkali metal borohydride is selected from one or more combinations of lithium borohydride, sodium borohydride, and potassium borohydride. The alkaline earth metal borohydride is selected from one or a combination of two of magnesium borohydride and calcium borohydride.

4. The catalytic system for the preparation of amine compounds by nitro reduction according to claim 1, characterized in that, The copper salt Lewis acid is selected from one or more combinations of copper chloride, cuprous chloride, copper acetate, copper sulfate, and cuprous sulfate; The other Lewis acids are selected from one or more combinations of cobalt chloride, cobalt acetate, ferric chloride, zinc chloride, zinc bromide, zinc acetate, manganese chloride, manganese acetate, and palladium trifluoroacetate.

5. The application of the catalytic system according to any one of claims 1 to 4 in the reduction of aromatic nitro compounds to prepare aromatic amine compounds, characterized in that, Includes the following steps: Step S1: Add the aromatic nitro compound and the catalyst to the aqueous solution of the alkali metal hydroxide, and heat the reaction system to 40-60°C to form a reaction substrate containing the catalyst; Step S2: The reducing agent is added to the catalyst-containing reaction substrate formed in step S1 in batches to reduce the aromatic nitro compound. The reaction temperature is controlled at 75-100℃. After the reaction is completed, a reaction solution containing aromatic amine compounds is obtained. Step S3: The reaction solution containing aromatic amine compounds obtained in step S2 is post-processed to obtain aromatic amine compound products; The aromatic nitro compound is represented by formula I: In Equation 1, R 1 R 2 R 3 R 4 R 5 and R 6 Each group independently represents nitro, hydrogen, deuterium, halogen, cyano, p-toluenesulfonyl, substituted or unsubstituted (C1-C2). 12 )alkyl, substituted or unsubstituted (C3-C 12 )cycloalkyl, substituted or unsubstituted (C1-C 12 )alkoxy, substituted or unsubstituted (C6-C 30 ) aryl, substituted or unsubstituted (3 to 12) heteroaryl, and R 1 R 2 R 3 R 4 R 5 and R 6 It contains at least one nitro group and at most three nitro groups simultaneously; The (C1-C) 12 )alkyl, (C3-C 12 )cycloalkyl and (C1-C 12 The substituents on the alkoxy group are one or more halogens or hydroxyl groups; The (C6-C) 30 The substituents on the aryl or (3- to 12-membered) heteroaryl group are selected from one or more of C1-C4 alkyl, C1-C4 alkoxy, halogen, hydroxyl, p-toluenesulfonyl, or trifluoromethyl.

6. The application according to claim 5, characterized in that, The R mentioned 1 R 2 R 3 R 4 R 5 and R 6 Independently nitro, hydrogen, deuterium, substituted or unsubstituted (C1-C) 12 )alkyl, substituted or unsubstituted (C1-C 12 )alkoxy; The (C1-C) 12 )alkyl, (C1-C 12 The substituents on the alkoxy group are one or more of halogens or hydroxyl groups.

7. The application according to claim 5, characterized in that, In step S1, a low-carbon alcohol organic solvent may or may not be added; When a low-carbon alcohol organic solvent is added, the low-carbon alcohol organic solvent is at least one of methanol, ethanol, isopropanol, and tert-butanol; The mass-to-volume ratio of the aromatic nitro compound to the low-carbon alcohol organic solvent is 1:(0.1-0.5) kg / L.

8. The application according to claim 5, characterized in that, In step S1, the molar ratio of the aromatic nitro compound: alkali metal hydroxide: catalyst is 1:(2.0-2.5):(0.04-0.08); In step S2, the molar ratio of the aromatic nitro compound to the reducing agent is 1:(2.0-2.5).

9. The application according to claim 5, characterized in that, In step S2, the batch feeding is carried out 5-30 times, the reaction temperature is controlled at 75-80℃, the time interval between each batch feeding is 5-60 minutes, and the reaction is continued for 2-5 hours after the feeding is completed.

10. The application according to claim 5, characterized in that, The post-processing described in step S3 includes: After the reaction is complete, the mixture is cooled, allowed to stand, and the phases are separated. The organic phase is then filtered, extracted, concentrated, and then 2wt%-8wt% potassium hydroxide and / or sodium hydroxide are added and mixed. After mixing, the mixture is distilled to obtain the aromatic amine compounds.

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