A method for preparing meta-nitro aromatic ring compounds

Abstract

The present invention relates to the technical field of organic chemistry, and particularly to a preparation method of m-nitroaromatic compounds, comprising the following steps: Step a, the amino group of the amphetamine compound is covalently linked to the auxiliary positioning group R4-SO3H to obtain the intermediate M1; Step b, the intermediate M1 reacts with alkyl nitrate to achieve meta-nitration of the benzene ring and obtain the intermediate M2; Step c, the auxiliary positioning group R4-SO3H in the intermediate M2 is removed to obtain the m-nitroamphetamine compound. The present application provides a brand-new solution, which realizes the meta-regioselective nitration of the benzene ring that is difficult to achieve by other methods in a simple and efficient manner, and provides an efficient and concise preparation method for m-nitroamphetamine compounds.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemistry, and in particular to a method for preparing a meta-nitro aromatic ring compound. Background Art

[0002] Nitration is a basic organic chemical reaction, and in the nitration of common monosubstituted aromatic ring substances, there is an obvious positioning effect. There is an obvious ortho / para-position positioning effect in the electron-donating group, and there is an obvious meta-position positioning effect in the electron-withdrawing group: this phenomenon is also called regioselectivity. As, amphetamine compounds are a class of widely used organic compounds, and in using conventional nitration reaction conditions (mixed acid of the composition of sulfuric acid / nitric acid), it can be realized that the phenylalanine nitration reaction realizes 95% para-selectivity. The case of reversing the regioselectivity of the monosubstituted benzene ring nitration reaction by a simple way is rare, and is limited to individual case reports, such as the reversal of the nitration regioselectivity of toluene: Hitomi Suzuki et al. reported the use of O in 1994 (Journal of the Chemical Society, Chemical Communications, 1994, 12, 1443-1444). 3 / NO 2 NO generated from mixed gas 3 The addition reaction is carried out at the para position of toluene, and the resulting cationic radical occupies the para position of the methyl group, and then further nitrates to eliminate HNO 3 The selectivity of the meta position can reach 77% (e.g. Figure 1 S.Sana et al. reported in 2009 (Synthetic Communications, 2009, 2949-2953) that the maximum yield of toluene meta-nitration can be 89% using an emulsion system composed of SDS / CTAB / Triton-X100, but the system has no effect of reversing the regioselectivity for other ortho / para-directing groups (such as OH groups). For other benzene rings containing ortho / para-directing groups, especially those containing other functional groups (such as amine, carboxyl, hydroxyl, etc.) on the directing groups, it is unique to achieve a simple and highly selective meta-nitration method by reversing the regioselectivity in a simple way. Summary of the invention

[0003] The object of the present invention is to provide a method for preparing a meta-nitro aromatic ring compound to solve the problems raised in the above background technology.

[0004] To achieve the above object, the present invention provides the following technical solutions:

[0005] A method for preparing a meta-nitro aromatic ring compound comprises the following steps:

[0006] Step 1: The amine group of the amphetamine compound is connected to the auxiliary positioning group R through a covalent bond 4 -SO 3 H, to obtain intermediate M 1 ;

[0007] Step 2: Intermediate M 1 Put it into a box to react with alkanol nitrate to achieve meta-nitration of the benzene ring to obtain intermediate M2;

[0008] Step 3: Removal of intermediate M 2 The auxiliary positioning base R 4 -SO 3 H, to obtain meta-nitroamphetamine compounds.

[0009] As a preferred solution of the present invention, the auxiliary positioning group R 4 -SO 3 H is composed of three components: M, linker part and sulfonic acid group, M is selected from carbonyl, sulfonyl or phosphoryl, M and SO 3 H is connected via a linker, and the minimum number of atomic connections between the two is an integer from 1 to 3.

[0010] As a preferred solution of the present invention, in step 2, the intermediate M 1 The reaction with alkanol nitrate does not require the addition of an additional catalyst, and only requires the addition of a reaction solvent to proceed smoothly.

[0011] As a preferred embodiment of the present invention, the alkanol nitrate is selected from a mixture of multiple C1-C8 alkanol nitrates, preferably C2-C6 alkanol nitrates, and the reaction solvent is selected from a mixture of several selected from dichloromethane, dichloroethane, chloroform, C4-C8 ethers, C3-C8 saturated lipids, C6-C20 alkanes or acetonitrile.

[0012] As a preferred solution of the present invention, in step 3, the auxiliary positioning group R is removed 4 -SO 3 The conditions of H are selected from acidic or alkaline aqueous solution systems, preferably from M 2 The aqueous solution was directly refluxed for reaction.

[0013] As a preferred solution of the present invention, a mixing chamber is provided in the box body, an electric heating wire is installed in the wall of the box body at the mixing chamber, a feed port communicating with the mixing chamber is provided at the center of the upper surface of the box body, a refrigerator is installed on the outer wall of the box body, the output port of the refrigerator is communicated with the interior of the mixing chamber through two cooling pipes, an inspection chamber is provided in the box body below the mixing chamber, a hydraulic cylinder is provided in the inspection chamber, a stirring assembly is installed at the telescopic end of the hydraulic cylinder, and the stirring assembly is located in the mixing chamber.

[0014] As a preferred solution of the present invention, a sealing cover is threadedly installed on the feed port, the two cooling tubes are symmetrically arranged on both sides of the feed port, a temperature sensor is installed on the top of the inner wall of the mixing chamber, a controller is installed on the outer wall of the box body away from the refrigerator, and the outer wall of the box body is hingedly connected to a sealing door at the inspection cavity.

[0015] As a preferred solution of the present invention, a plurality of ball bearings are embedded on the bottom plate of the inspection chamber, a movable plate is placed on the plurality of ball bearings, outer walls of the movable plate are in contact with the inner wall of the inspection chamber and the inner wall of the sealing door, sliding grooves are provided on both side outer walls of the movable plate, sliders are fixed on both side inner walls of the inspection chamber, and the two sliders are matched with the sliding grooves and are slidably connected.

[0016] As a preferred solution of the present invention, the stirring assembly includes a mounting plate, which is fixed to the telescopic end of the hydraulic cylinder, a blocking block is provided above the mounting plate, a stirring rod is vertically provided on the upper surface of the blocking block, a stirring blade is fixedly installed on the outer wall of the stirring rod, the blocking block passes through the top of the inspection cavity and is sealed with the contact part by a sealing layer, a stirring motor is fixed between the mounting plate and the blocking block by bolts, and the output end of the stirring motor passes through the blocking block and is connected to the bottom end flange of the stirring rod.

[0017] As a preferred solution of the present invention, a drain port is provided on one side of the bottom of the mixing chamber on the outer wall of the box body, the inner bottom surface of the drain port is set to an inclined surface, a matching baffle is provided at one end of the drain port close to the mixing chamber, an electric telescopic rod is fixedly connected to the outer wall of the baffle, a fixing plate is installed on the top of one end of the drain port located on the outer wall of the box body, and the electric telescopic rod is fixedly connected to the inner wall of the fixing plate by bolts.

[0018] Compared with the prior art, the present invention has the following beneficial effects: in response to the problems raised by the background technology, the present application creatively adopts a method of connecting an easily removable auxiliary directing group containing a sulfonic acid group at the end to the amine group of amphetamines, and uses alkanol nitrate as a nitrating agent, thereby achieving the reversal of the regioselectivity of the nitration reaction of amphetamine compounds (the side chain containing an amine group is an ortho / para directing group), and achieving the efficient preparation of meta-nitroamphetamine compounds, wherein the meta-selectivity of ethyl phenylalanine can reach up to 97%. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 For the present invention 3 / NO 2 Combined meta-nitration diagram for simple benzene rings;

[0020] Figure 2 Schematic diagram of bond nitration of phenylalanine of the present invention;

[0021] Figure 3 is a meta-nitration route map of the amphetamine compounds of the present invention;

[0022] Figure 4 It is a structural diagram of a part of the auxiliary positioning base of the present invention;

[0023] Figure 5 It is a schematic diagram of the box of the present invention;

[0024] Figure 6 For the present invention Figure 5 Internal cross-sectional structure diagram;

[0025] Figure 7 This is an enlarged view of point A of the present invention.

[0026] In the figure: 1. Box body; 101. Mixing chamber; 102. Feed inlet; 1021. Sealing cover; 103. Controller; 104. Inspection chamber; 1041. Sliding block; 1042. Ball bearing; 105. Sealing door; 2. Stirring assembly; 201. Mounting plate; 202. Stirring motor; 203. Blocking block; 204. Stirring rod; 2041. Stirring blade; 3. Electric heating wire; 4. Temperature sensor; 5. Cooling pipe; 501. Refrigerator; 6. Drain port; 601. Inclined surface; 602. Baffle; 603. Electric telescopic rod; 604. Fixed plate; 7. Hydraulic cylinder; 701. Moving plate; 7011. Slideway. DETAILED DESCRIPTION

[0027] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0028] In order to facilitate understanding of the present invention, the present invention will be described more fully below with reference to the relevant drawings. Several embodiments of the present invention are given. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present invention more thorough and comprehensive.

[0029] It should be noted that when an element is referred to as being "fixed to" another element, it may be directly on the other element or there may be a central element. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be a central element at the same time. The terms "vertical", "horizontal", "left", "right" and similar expressions used herein are for illustrative purposes only.

[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0031] See also Figure 1-4 , the present invention provides a technical solution:

[0032] A method for preparing a meta-nitro aromatic ring compound comprises the following steps:

[0033] Step 1: The amine group of the amphetamine compound is connected to the auxiliary positioning group R through a covalent bond 4 -SO 3 H, to obtain intermediate M 1 ;

[0034] Step 2: Intermediate M 1 Reaction with alkanol nitrate to achieve meta-nitration of the benzene ring to obtain intermediate M 2 ;

[0035] Step 3: Removal of intermediate M 2 The auxiliary positioning base R 4 -SO 3 H, to obtain meta-nitroamphetamine compounds.

[0036] This method is an indirect nitration method, not a direct one-step reaction. The structure of amphetamine compounds is as follows Figure 2 The product is shown in Formula 2. Wherein the substituent group R on the benzene ring 1 is halogen, alkoxy, amine, amide, alkyl or aryl, and the substitution site can be 2, 3 or 4; group R 2 is H, alkyl, carboxyl, alkoxycarbonyl, aminocarbonyl or cyano; group R 3 is H or alkyl.

[0037] Among them, the auxiliary positioning base R 4 -SO 3 The structure of H is shown below,

[0038]

[0039] M is selected from carbonyl, sulfonyl or phosphoryl, and M and SO 3 H is connected through a linker, and the minimum number of atoms connected between the two is an integer of 1-3. The linker part can be a straight chain, branched chain or cyclic, and part of the auxiliary positioning group R 4 -SO 3 H Figure 4 shown.

[0040] Intermediate M 1 The reaction with the alkyl nitrate does not require the addition of an additional catalyst, and the reaction can proceed by simply adding a reaction solvent, wherein the alkyl nitrate is selected from one or a mixture of C1-C8 alkyl nitrates, preferably C2-C6 alkyl nitrates, and the reaction solvent is selected from one or a mixture of dichloromethane, dichloroethane, chloroform, C4-C8 ethers, C3-C8 saturated lipids, C6-C20 alkanes or acetonitrile.

[0041] In step 3, the auxiliary positioning group R is removed. 4 -SO 3 The conditions of H are selected from acidic or alkaline aqueous solution systems, preferably from M 2 The aqueous solution was directly refluxed for reaction.

[0042] By connecting an easily removable auxiliary directing group containing a sulfonic acid group at the end to the amine group of amphetamines and using alkanol nitrates as nitrating agents, the regioselectivity of the nitration reaction of amphetamine compounds (the side chain containing an amine group is an ortho / para directing group) can be reversed, thereby achieving the efficient preparation of meta-nitroamphetamine compounds, among which the meta-selectivity of ethyl phenylalanine can reach as high as 97%.

[0043] Example 1: Effect of linker length (Formula 3) on nitration regioselectivity.

[0044] Experimental procedure: The mixture of L-phenylalanine ethyl ester hydrochloride (compound a, 1.0 g), dichloromethane (10 mL), water (10 mL), and sodium bicarbonate (1.0 g) was cooled to 0°C, and Cl(CH 2 ) n COCl (1.2 eq, n is 1-6 respectively), continue stirring after the addition is complete until the reaction is complete, separate the liquids and concentrate the organic phase to dryness (to obtain compound b), add ethanol (15 mL), NaHSO 3 (0.68g) was heated to reflux for 3h, cooled to room temperature and filtered, and the filtrate was concentrated to dryness to obtain phenylalanine ethyl ester (compound c) connected to the linker. The obtained mixture of compound c, dichloromethane (25mL) and isopropyl nitrate (0.92g) was reacted at 20-30℃ for 18h. After the reaction was completed, 10mL of water was added and the organic solvent was removed by concentration at 30℃. The obtained aqueous solution was heated to reflux for about 10h, cooled to 0℃ and then treated with NaHCO 3The solid is adjusted to pH 6-7, and the precipitated solid is filtered to obtain nitrophenylalanine. The test results show that the content ratios of meta-nitration products / ortho+para-nitration products are: 91:9 (n=1), 94:6 (n=2), 81:19 (n=3), 38:62 (n=4), 4:96 (n=5), and 0.7:99.3 (n=6). The experimental results show that when n>3, the proportion of meta-nitration decreases rapidly.

[0045]

[0046] Example 2: Kilogram-scale preparation of L-m-nitrophenylalanine.

[0047] Add L-phenylalanine ethyl ester hydrochloride (2.0kg), water (20kg), and ethanol (2kg) to a 50L double-layer glass reactor, cool to 0℃, add solid sodium bicarbonate (1.92kg) in batches, continue stirring for 15 minutes after addition, and add 2-chloroacetyl chloride (1.5kg) dropwise, which takes about 2h. After stirring for 30 minutes after addition, add dichloromethane (10 kg), stir for 10 minutes and separate the liquids. The aqueous phase is extracted once with dichloromethane (4kg), and the organic phases are combined and concentrated to dryness by rotary evaporation under reduced pressure at 20℃ to form a light yellow viscous liquid. Add ethanol (total amount 24kg) to the rotary evaporator in batches to dissolve the product and transfer it to a 50L double-layer glass reactor, and add NaHSO 3 The mixture was stirred with 2.6 kg of ethyl acetate and 0.3 kg of n-heptane, and refluxed for 2 h. The mixture was cooled to 30 °C and filtered. The filter cake was rinsed once with 5 kg of ethanol. The filtrates were combined and concentrated to dryness under reduced pressure. Ethyl acetate (3 kg) and n-heptane (5 kg) were added. The mixture was slurried for 30 min and filtered. The filter cake was vacuum dried at 40 °C for 6 h to obtain 3.11 kg of white solid.

[0048] 88 kg of dichloromethane and the white solid obtained above were added to a 200 L glass-lined reactor in sequence, and isopropyl nitrate (2.2 kg) was added when the temperature was lowered to 0-10°C, and the temperature was controlled at 15-25°C for 24 hours. 30 kg of water was added to the system, and the dichloromethane was removed by vacuum concentration, and then the temperature was slowly raised to reflux, and the reaction was continued for 12 hours. After cooling to room temperature, the pH was adjusted to between 3-4 with 40% NaOH, and then the pH was slowly adjusted to between 6.5-7.5 with solid sodium bicarbonate, and the temperature was lowered to 0-5°C and stirred for crystallization for 3 hours, centrifuged and filtered, and the filter cake was washed with water until the filtrate was treated with 5% Ba(OH), and no obvious precipitation was detected, and 1.83 kg of off-white solid was obtained. The test results showed that the content ratio of meta-nitration product / ortho+para-position product was 97:3, and the raw material remained 0.8%.

[0049] Example 3: Meta-nitration reaction of amphetamine.

[0050]

[0051] Amphetamine (compound e, 5 g), acetonitrile (50 mL), and 2-sulfobenzoic anhydride (compound f, 7.6 g) were mixed at 0°C and then slowly heated to 50°C for 1.5 h to obtain an acetonitrile solution of compound g. Acetonitrile (50 mL) and n-butyl nitrate (5.5 g) were added to the solution and stirred for 6 h. The solvent was removed by concentration under reduced pressure, 50 mL of water was added, and the temperature was refluxed vigorously for 9 h. After cooling to room temperature, dichloromethane (50 mL) and 20% N 2 OH was used to adjust the pH of the aqueous phase to >10, and the liquids were separated, and the aqueous phase was extracted with dichloromethane (20 mLx2). The combined organic phases were dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure to obtain 6.6 g of a yellow oil, namely, m-nitroamphetamine (compound i), with a total yield of 96%.

[0052] Example 4: Meta-nitration reaction of 2-(3-methoxyphenyl)ethylamine.

[0053] A mixture of 1.2-ethanedisulfonic acid (2 g) and dichlorothionyl (1.25 g) was refluxed at 80°C until no more gas was released in the system, and then vacuumed and decompressed for 1 hour to obtain ethanedisulfonic anhydride solid powder. After removing the vacuum, dioxane (20 mL) and compound j (1.55 g) were added to the reaction system, stirred at 50°C for 2 hours to obtain a dioxane solution of compound k, and the reaction temperature was lowered to -5°C, isopropyl nitrate (3.3 g, 3.0 eq) was added, and the reaction was stirred at -5°C for 12 hours to complete the reaction. 100 mL of n-heptane was added to the reaction solution, and the precipitated solid matter was filtered to obtain compound i. Compound i was dissolved in 15 mL of water, heated to 90 ° C for 6 h to stop the reaction, cooled to room temperature, and then adjusted to pH>13 with 10% NaOH. It was extracted three times with tert-methyl ether (20 mL each time), and the combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 1.48 g of 2-(3-methoxy-5-nitrophenyl)ethylamine with a yield of 72%, i.e., compound m.

[0054]

[0055] For examples, see Figure 5-7A mixing chamber 101 is provided in the box body 1, an electric heating wire 3 is installed in the wall of the box body 1 at the mixing chamber 101, a feed port 102 communicating with the mixing chamber 101 is provided at the center of the upper surface of the box body 1, a refrigerator 501 is installed on the outer wall of the box body 1, and the output port of the refrigerator 501 is communicated with the inside of the mixing chamber 101 through two cooling pipes 5, an inspection chamber 104 is provided in the box body 1 below the mixing chamber 101, a hydraulic cylinder 7 is provided in the inspection chamber 104, a stirring assembly 2 is installed at the telescopic end of the hydraulic cylinder 7, the stirring assembly 2 is located in the mixing chamber 101, and the feed port 102 is provided at the center of the upper surface of the box body 1. 2 is threadedly installed with a sealing cover 1021, two cooling pipes 5 are symmetrically arranged on both sides of the feed port 102, a temperature sensor 4 is installed on the top of the inner wall of the mixing chamber 101, a controller 103 is installed on the outer wall of the box body 1 away from the refrigerator 501, and the outer wall of the box body 1 is located at the inspection chamber 104 and is hingedly connected with a sealing door 105, a plurality of balls 1042 are embedded on the bottom plate of the inspection chamber 104, and a movable plate 701 is placed on the plurality of balls 1042, and the outer walls of the movable plate 701 are in contact with the inner wall of the inspection chamber 104 and the inner wall of the sealing door 105, and the outer walls on both sides of the movable plate 701 A slide groove 7011 is provided, and sliders 1041 are fixed to the inner walls on both sides of the inspection chamber 104. The two sliders 1041 match the slide groove 7011 and are slidably connected. The stirring assembly 2 includes a mounting plate 201, and the mounting plate 201 is fixed to the telescopic end of the hydraulic cylinder 7. A blocking block 203 is provided above the mounting plate 201. A stirring rod 204 is vertically provided on the upper surface of the blocking block 203. A stirring blade 2041 is fixedly installed on the outer wall of the stirring rod 204. The blocking block 203 passes through the top of the inspection chamber 104 and is sealed with the contact part through a sealing layer. The mounting plate 201 and the blocking block 20 3 is fixed with a stirring motor 202 by bolts, the output end of the stirring motor 202 passes through the blocking block 203 and is connected to the bottom flange of the stirring rod 204, the outer wall of the box body 1 is located at the bottom side of the mixing chamber 101 and is provided with a drain port 6, the inner bottom surface of the drain port 6 is set as an inclined surface 601, and the end of the drain port 6 close to the mixing chamber 101 is provided with a matching baffle 602, the outer wall of the baffle 602 is fixedly connected with an electric telescopic rod 603, and the top of the end of the drain port 6 located on the outer wall of the box body 1 is installed with a fixing plate 604, and the electric telescopic rod 603 is fixedly connected to the inner wall of the fixing plate 604 by bolts.

[0056] When the meta-nitration reaction of amphetamine is carried out, the staff starts the refrigerator 501 through the controller 103, and the cold air generated by the refrigerator 501 is sent into the mixing chamber 101 through the cooling tube 5 to reduce the internal temperature to 8°C. Then the sealing cover 1021 is rotated to expose the opening of the feed port 102, and the staff introduces amphetamine, acetonitrile, and 2-sulfobenzoic anhydride into the mixing chamber 101 from the feed port 102. Then the controller 103 starts the stirring assembly 2, and the stirring motor 202 starts its output end to drive the stirring rod 204 to rotate. The rotating stirring rod 204 drives the stirring blade 2041 to rotate, thereby mixing the added compounds. Then the refrigerator 501 stops working, and the electric heating wire 3 is started to raise the temperature in the mixing chamber 101 to 50°C. After reacting for 1.5 hours, an acetonitrile solution of compound g is obtained, and then acetonitrile and n-butyl nitrate are added through the feed port 102, and the stirring reaction is continued for 6 hours through the stirring blade 2041. After h, the controller 103 starts the electric telescopic rod 603, and the electric telescopic rod 603 drives the baffle 602 to move to cancel the blockage of the drain port 6. The reacted solution is discharged from the box 1 from the drain port 6 for collection, and then the collected solution is sent to the vacuum concentrator for subsequent operations. When the stirring component 2 needs to be maintained, the sealing door 105 is opened to expose the inspection chamber 104, and then the hydraulic cylinder 7 is started by the controller 103. The hydraulic cylinder 7 drives the mounting plate 201 to move downward. The downwardly moved mounting plate 201 drives the blocking block 203 to move downward through the stirring motor 202. The downwardly moved blocking block 203 drives the stirring rod 204 and the stirring blade 2041 to move downward, so that they are moved into the inspection chamber 104, and then the staff pulls the movable plate 701 outward. Under the action of the ball 1042 and the slide groove 7011, the movable plate 701 can easily drive the components arranged above to move out of the inspection chamber 104, so as to facilitate the maintenance and repair of the stirring component 2.

[0057] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a meta-nitro aromatic ring compound, It is characterized in that The following steps are involved: Step a: The compound of formula 1 is connected to the auxiliary positioning group R via a covalent bond. 4 -SO 3 H, to obtain intermediate M 1 ; Step b: intermediate M 1 and alkyl nitrate in a box (1) to react, achieving meta-nitration of the benzene ring to obtain the intermediate M 2 ; Step c, removal of intermediate M 2 The auxiliary positioning base R 4 -SO 3 H, to obtain m-nitroamphetamine compounds; The substituent group R on the benzene ring 1 It is halogen, alkoxy, amine, amide, alkyl, or aryl, and the substitution site can be 2, 3, or 4; Group R 2 is H, alkyl, carboxyl, alkoxycarbonyl, aminocarbonyl, cyano; Group R 3 is H or alkyl; The auxiliary positioning base R 4 -SO 3 H is divided into three components: M, linker part and sulfonic acid group. The structure is shown below. M is selected from carbonyl, sulfonyl or phosphoryl, and M and SO 3 H is connected via a linker, and the minimum number of atomic connections between the two is an integer from 1 to 3.

2. A method for preparing a meta-nitro aromatic ring compound according to claim 1, It is characterized in that In the step b, the intermediate M 1 The reaction with alkanol nitrate does not require the addition of an additional catalyst, and the reaction can be carried out by adding a reaction solvent.

3. A method for preparing a meta-nitro aromatic ring compound according to claim 2, It is characterized in that The alkanol nitrate is selected from one or a mixture of C1-C8 alkanol nitrates, and the reaction solvent is selected from one or a mixture of dichloromethane, dichloroethane, chloroform, C4-C8 ether, C3-C8 saturated fat, C6-C20 alkane or acetonitrile.

4. A method for preparing a meta-nitro aromatic ring compound according to claim 3, It is characterized in that The alkanol nitrate is selected from C2-C6 alkanol nitrate.

5. A method for preparing a meta-nitro aromatic ring compound according to claim 1, It is characterized in that In the step c, the auxiliary positioning group R is removed 4 -SO 3 The condition of H is selected from an acidic or alkaline aqueous solution system, and the reaction is directly refluxed.

6. A method for preparing a meta-nitro aromatic ring compound according to claim 5, It is characterized in that The aqueous solution system is an aqueous solution of M 2 .

7. A method for preparing a meta-nitro aromatic compound according to claim 1, It is characterized in that A mixing chamber (101) is provided in the box body (1), an electric heating wire (3) is installed in the wall of the box body (1) at the mixing chamber (101), a feed port (102) communicating with the mixing chamber (101) is provided at the center of the upper surface of the box body (1), a refrigerator (501) is installed on the outer wall of the box body (1), the output port of the refrigerator (501) is communicated with the inside of the mixing chamber (101) through two cooling pipes (5), an inspection chamber (104) is provided in the box body (1) below the mixing chamber (101), a hydraulic cylinder (7) is provided in the inspection chamber (104), a stirring assembly (2) is installed at the telescopic end of the hydraulic cylinder (7), and the stirring assembly (2) is located in the mixing chamber (101).

8. A method for preparing a meta-nitro aromatic ring compound according to claim 7, It is characterized in that A sealing cover (1021) is threadedly mounted on the feed port (102), the two cooling tubes (5) are symmetrically arranged on both sides of the feed port (102), a temperature sensor (4) is mounted on the top of the inner wall of the mixing chamber (101), a controller (103) is mounted on the outer wall of the box body (1) away from the refrigerator (501), and a sealing door (105) is hingedly connected to the outer wall of the box body (1) at the inspection chamber (104); A plurality of ball bearings (1042) are embedded on the bottom plate of the inspection chamber (104), a movable plate (701) is placed on the plurality of ball bearings (1042), the outer walls of the movable plate (701) are in contact with the inner walls of the inspection chamber (104) and the inner walls of the sealing door (105), sliding grooves (7011) are provided on the outer walls on both sides of the movable plate (701), and sliding blocks (1041) are fixed on the inner walls on both sides of the inspection chamber (104), and the two sliding blocks (1041) are matched with the sliding grooves (7011) and are slidably connected.

9. A method for preparing a meta-nitro aromatic ring compound according to claim 8, It is characterized in that The stirring assembly (2) comprises a mounting plate (201), the mounting plate (201) being fixed to the telescopic end of the hydraulic cylinder (7), a blocking block (203) being provided above the mounting plate (201), a stirring rod (204) being vertically provided on the upper surface of the blocking block (203), a stirring blade (2041) being fixedly mounted on the outer wall of the stirring rod (204), the blocking block (203) penetrating the top of the inspection cavity (104) and being sealed with the contact part by a sealing layer, a stirring motor (202) being fixed between the mounting plate (201) and the blocking block (203) by bolts, and an output end of the stirring motor (202) passing through the blocking block (203) and being flange-connected to the bottom end of the stirring rod (204).

10. The method for preparing a meta-nitro aromatic ring compound according to claim 7, It is characterized in that The outer wall of the box body (1) is provided with a liquid discharge port (6) at one side of the bottom of the mixing chamber (101); the inner bottom surface of the liquid discharge port (6) is provided as an inclined surface (601); a matching baffle plate (602) is provided at one end of the liquid discharge port (6) close to the mixing chamber (101); an electric telescopic rod (603) is fixedly connected to the outer wall of the baffle plate (602); a fixing plate (604) is installed at the top of one end of the liquid discharge port (6) located on the outer wall of the box body (1); and the electric telescopic rod (603) is fixedly connected to the inner wall of the fixing plate (604) by bolts.

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