A preparation method of 6-chloro-2,3-diaminotoluene and an intermediate

Abstract

The present invention relates to the field of organic chemistry, and a preparation method and an intermediate of 6-chloro-2,3-diaminotoluene are provided. The present invention carries out oxime etherification reaction by phenanthrenequinone and alkoxylamine or alkoxylamine salt, obtains phenanthrenequinone bis-oxime ether structural compound, then carries out cycloaddition reaction by phenanthrenequinone bis-oxime ether structural compound and 2,6-dichlorotoluene, and the cycloaddition product is subjected to hydrogenolysis reaction, and 6-chloro-2,3-diaminotoluene and 9,10-dihydrophenanthrene are obtained. The preparation method of the present invention has easy-to-obtain raw materials, low production cost, and high product yield; isomer impurities substituted by other sites on the benzene ring are produced, and no column chromatography purification is required, which is suitable for industrial production; the present invention can also generate byproduct 9,10-dihydrophenanthrene while obtaining 6-chloro-2,3-diaminotoluene, and two highly economical compounds can be obtained at one time; and the present invention does not need to use high-pollution and high-energy-consuming zinc powder as a reducing agent, and the reaction conditions are mild and the energy consumption is small.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemistry, and in particular to a preparation method of 6-chloro-2,3-diaminotoluene and an intermediate. Background Art

[0002] Daridorexant (CAS: 1505484-82-1) is a dual orexin receptor (OXR) antagonist that competitively binds to OX1R and OX2R to inhibit orexin signaling, thereby blocking the overactive wakefulness pathway in insomnia patients to treat adult insomnia patients. It can strongly inhibit the two orexin receptors, is rapidly absorbed, and thus helps to fall asleep, and also has good pharmacokinetic characteristics. The synthesis route reported in the original patent (WO2013 / 182972) is as follows:

[0003]

[0004] Among them, 6-chloro-2,3-diaminotoluene (CAS No.: 673487-36-0) is an important intermediate of Daridorexant. Existing patents and literature rarely report the synthesis of 6-chloro-2,3-diaminotoluene. [Journal of the Chemical Society, 1920, vol. 117, p. 789] uses o-chlorotoluene as a raw material, and obtains 6-chloro-2,3-dinitrotoluene through a two-step nitration reaction, and then reduces it with zinc powder to obtain 6-chloro-2,3-diaminotoluene. The formula is as follows:

[0005]

[0006] Since there are many reaction sites in the two-step nitration, isomer separation is difficult, and it is difficult to carry out the next nitration after the first step of nitration due to benzene ring passivation, which is particularly unsuitable for industrial production. Summary of the invention

[0007] In view of this, the present invention provides a preparation method of 6-chloro-2,3-diaminotoluene and an intermediate. The preparation method provided by the present invention has easy-to-obtain raw materials, low cost, avoids the problem of isomerization, does not require zinc powder reduction, has high economic value, and is extremely practical.

[0008] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0009] A method for preparing 6-chloro-2,3-diaminotoluene comprises the following steps:

[0010] (1) Under the action of a first alkaline reagent, phenanthrenequinone and an alkoxyamine or an alkoxyamine salt are subjected to an oxime etherification reaction in a solvent to obtain a phenanthrenequinone bisoxime ether structure compound; the alkoxyamine is an alkoxyamine or a benzyloxyamine; the number of carbon atoms in the alkoxyamine is 1 to 4; the phenanthrenequinone bisoxime ether structure compound has a structural formula as shown in Formula I:

[0011]

[0012] In formula I: R is C 1-4 Alkyl or benzyl;

[0013] (2) Under the action of a second alkaline reagent, the phenanthrenequinone bisoxime ether structure compound is subjected to a cycloaddition reaction with 2,6-dichlorotoluene in a solvent to obtain a compound having a structure shown in Formula II;

[0014]

[0015] In formula II: R is C 1-4 Alkyl or benzyl;

[0016] (3) Mixing the compound having the structure shown in Formula II, a metal catalyst and a solvent for hydrogenolysis reaction to obtain 6-chloro-2,3-diaminotoluene and 9,10-dihydrophenanthrene.

[0017] Preferably, the first alkaline agent is sodium acetate; the molar ratio of the phenanthrenequinone to the first alkaline agent is 1:4-8;

[0018] The molar ratio of phenanthrenequinone to alkoxyamine or alkoxyamine salt is 1:2-4;

[0019] The solvent for the oxime etherification reaction is one or more of water, alcohol solvents, furan solvents and dimethyl sulfoxide.

[0020] Preferably, the temperature of the oxime etherification reaction is 10-70° C., and the time is 2-12 hours.

[0021] Preferably, the molar ratio of the phenanthrenequinone bisoxime ether structure compound to 2,6-dichlorotoluene is 1:1 to 5;

[0022] The second alkaline agent is one or more of n-butyl lithium, sec-butyl lithium, tert-butyl lithium, lithium diisopropylamide, potassium amide, sodium amide and sodium bis(trimethylsilyl)amide; the molar ratio of the phenanthrenequinone bisoxime ether structure compound to the second alkaline agent is 1:1-4;

[0023] The solvent for the cycloaddition reaction is one or more of toluene, acetonitrile, diethyl ether, 1,4-dioxane, dichloromethane and tetrahydrofuran.

[0024] Preferably, the temperature of the cycloaddition reaction is -100 to 0°C, and the reaction time is 6 to 18 hours.

[0025] Preferably, the metal catalyst is one or more of Rh / C, Pd / C, Pt / C, Raney nickel and Raney cobalt; the mass of the metal catalyst is 2% to 30% of the mass of the compound having the structure shown in Formula II.

[0026] Preferably, the solvent for the hydrogenolysis reaction is one or more of water, dichloromethane, furan solvents, 1,4-dioxane and alcohol solvents.

[0027] Preferably, the hydrogen pressure of the hydrogenolysis reaction is 0.2-1 MPa, the reaction temperature is 0-80° C., and the reaction time is 5-15 h.

[0028] The present invention also provides an intermediate for synthesizing 6-chloro-2,3-diaminotoluene, which has a structure shown in Formula II:

[0029]

[0030] In formula II, R is C 1-4 Alkyl or benzyl.

[0031] The present invention also provides a method for preparing the intermediate described in the above scheme, comprising the following steps:

[0032] The reaction is carried out according to the method described in steps (1) to (2) of the above scheme to obtain the intermediate.

[0033] The invention provides a method for preparing 6-chloro-2,3-diaminotoluene. The invention comprises the following steps: under the action of a first alkaline reagent, subjecting phenanthrenequinone and an alkoxyamine or an alkoxyamine salt to an oxime etherification reaction in a solvent to obtain a phenanthrenequinone bisoxime ether structure compound (the structural formula of which is shown above); then, under the action of a second alkaline reagent, subjecting the phenanthrenequinone bisoxime ether structure compound to a cycloaddition reaction with 2,6-dichlorotoluene in a solvent to obtain a compound having a structure shown in Formula II; and mixing the compound having a structure shown in Formula II, a metal catalyst and a solvent to carry out a hydrogenolysis reaction to obtain 6-chloro-2,3-diaminotoluene and 9,10-dihydrophenanthrene. The preparation method provided by the invention has readily available raw materials, is cheap, has relatively low production cost and high product yield; in addition, in the synthesis process of the invention, no isomer impurities substituted at other positions on the benzene ring are generated, so no column chromatography purification is required during post-treatment, which greatly reduces the difficulty of post-treatment and is suitable for industrial production; while obtaining 6-chloro-2,3-diaminotoluene, the invention can also generate a by-product 9,10-dihydrophenanthrene, so that two highly economical compounds can be obtained at one time, with high atomic economy and good economy; and 9,10-dihydrophenanthrene is a liquid under normal pressure, and can be separated from 6-chloro-2,3-diaminotoluene only by reduced pressure distillation, and the operation is simple.

[0034] Furthermore, in the traditional method, zinc powder is required in the last step to reduce the nitro group to the amino group, which is highly polluting and energy-consuming. However, the catalyst used in the present invention is a catalyst such as Pd / C, which avoids the use of highly polluting and energy-consuming zinc powder as a reducing agent, and the reaction conditions are mild and the energy consumption is low.

[0035] The present invention also provides an intermediate for preparing 6-chloro-2,3-diaminotoluene, which has a structure shown in Formula II. The intermediate of the present invention is used to prepare 6-chloro-2,3-diaminotoluene, which only requires one step of reaction, and can simultaneously obtain two products with high economic value, 6-chloro-2,3-diaminotoluene and 9,10-dihydrophenanthrene. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of 6-chloro-2,3-diaminotoluene prepared in Example 5 of the present invention;

[0037] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of 9,10-dihydrophenanthrene prepared in Example 5 of the present invention. DETAILED DESCRIPTION

[0038] The present invention provides a method for preparing 6-chloro-2,3-diaminotoluene, comprising the following steps:

[0039] (1) Under the action of a first alkaline reagent, phenanthrenequinone and an alkoxyamine or an alkoxyamine salt are subjected to an oxime etherification reaction in a solvent to obtain a phenanthrenequinone bisoxime ether structure compound; the alkoxyamine is an alkoxyamine or a benzyloxyamine; the number of carbon atoms in the alkoxyamine is 1 to 4; the phenanthrenequinone bisoxime ether structure compound has a structural formula as shown in Formula I:

[0040]

[0041] In formula I: R is C 1-4 Alkyl or benzyl;

[0042] (2) Under the action of a second alkaline reagent, the phenanthrenequinone bisoxime ether structure compound is subjected to a cycloaddition reaction with 2,6-dichlorotoluene and a base in a solvent to obtain a compound having a structure shown in Formula II;

[0043]

[0044] In formula II: R is C 1-4 Alkyl or benzyl;

[0045] (3) Mixing the compound having the structure shown in Formula II, a metal catalyst and a solvent for hydrogenolysis reaction to obtain 6-chloro-2,3-diaminotoluene and 9,10-dihydrophenanthrene.

[0046] In the present invention, the synthesis route of 6-chloro-2,3-diaminotoluene is as shown in Formula A:

[0047]

[0048] The preparation method of the present invention is described in detail below in conjunction with the synthesis route.

[0049] In the present invention, phenanthrenequinone and alkoxyamine or alkoxyamine salt are subjected to oxime etherification reaction in a solvent under the action of a first alkaline reagent to obtain a phenanthrenequinone bis-oxime ether structure compound. In the present invention, the alkoxyamine is an alkoxyamine or a benzyloxyamine; the number of carbon atoms in the alkoxyamine is 1 to 4; specifically, the alkoxyamine is preferably methoxyamine, ethoxyamine, n-propyloxyamine, isopropyloxyamine or n-butyloxyamine, more preferably methoxyamine; the alkoxyamine salt is preferably the hydrochloride of the above-mentioned alkoxyamine, more preferably methoxyamine hydrochloride or ethoxyamine hydrochloride.

[0050] In the present invention, the molar ratio of phenanthrenequinone to alkoxylamine or alkoxylamine salt is preferably 1:2-4, more preferably 1:2-3.

[0051] In the present invention, the first alkaline agent is preferably sodium acetate; the molar ratio of the phenanthrenequinone to the first alkaline agent is preferably 1:4-8.

[0052] In the present invention, the solvent for the oxime etherification reaction is preferably one or more of water, alcohol solvents, furan solvents and dimethyl sulfoxide; the alcohol solvent is preferably methanol or ethanol; the furan solvent is preferably tetrahydrofuran or 2-methyltetrahydrofuran; the present invention has no special requirements for the amount of the solvent, as long as it can make the reaction proceed smoothly.

[0053] In the present invention, the temperature of the oxime etherification reaction is preferably 10 to 70° C., more preferably 20 to 65° C.; the time of the oxime etherification reaction is preferably 2 to 12 h, more preferably 6 to 10 h.

[0054] After the oxime etherification reaction is completed, the present invention preferably evaporates the obtained product liquid to dryness, adds water to the obtained solid product for pulping and then filters it, washes the filter cake to obtain a phenanthrenequinone bis-oxime ether structure compound; the structural formula of the phenanthrenequinone bis-oxime ether structure compound is as shown in Formula I, and the R group in Formula I is preferably methyl, ethyl, n-propyl, isopropyl, n-butyl or benzyl, more preferably methyl.

[0055] After obtaining the phenanthrenequinone bisoxime ether structure compound, the present invention will carry out a cycloaddition reaction between the phenanthrenequinone bisoxime ether structure compound and 2,6-dichlorotoluene in a solvent under the action of a second alkaline reagent to obtain a compound having a structure shown in Formula II, wherein the type of the R group in Formula II is consistent with that in Formula I and is not repeated here. In the present invention, the second alkaline reagent is preferably one or more of n-butyl lithium, sec-butyl lithium, tert-butyl lithium, lithium diisopropylamide, potassium amide, sodium amide and sodium bis(trimethylsilyl)amide, more preferably lithium diisopropylamide or sec-butyl lithium; the molar ratio of the phenanthrenequinone bisoxime ether structure compound and the second alkaline reagent is preferably 1:1-4, more preferably 1:1-2; the molar ratio of the phenanthrenequinone bisoxime ether structure compound to 2,6-dichlorotoluene is preferably 1:1-5, more preferably 1:1-1.2; the solvent for the cycloaddition reaction is preferably one or more of toluene, acetonitrile, ether, 1,4-dioxane, dichloromethane and tetrahydrofuran; the present invention has no special requirements for the amount of the solvent, as long as it can make the reaction proceed smoothly.

[0056] In the present invention, the temperature of the cycloaddition reaction is preferably -100 to 0°C, more preferably -50 to -10°C, and the time of the cycloaddition reaction is preferably 6 to 18 hours; the cycloaddition reaction is preferably carried out under nitrogen protection.

[0057] In a specific embodiment of the present invention, 2,6-dichlorotoluene is preferably first dissolved in a solvent, the 2,6-dichlorotoluene solution is cooled to -55 to -25°C (preferably -50±5°C or -30±5°C), a second alkaline reagent is added dropwise to the 2,6-dichlorotoluene solution, and the mixture is stirred for 1 hour after the addition is completed, the phenanthrenequinone bisoxime ether structure compound is dissolved in the solvent, and the solution of the phenanthrenequinone bisoxime ether structure compound is added dropwise to the system at -55 to -25°C, and the mixture is stirred and reacted for 3 to 5 hours after the addition is completed, and then the mixture is heated to 0°C and the reaction is continued for 8 to 10 hours; in the present invention, the 2,6-dichlorotoluene generates a benzylene intermediate during the reaction, and then reacts with the phenanthrenequinone bisoxime ether structure compound to obtain the target product, and the specific process is shown in Formula B:

[0058]

[0059] After the cycloaddition reaction is completed, the present invention preferably adds a saturated ammonium chloride solution to the reaction solution to quench the reaction, extracts the obtained product solution with ethyl acetate, and spin-dries the obtained organic phase to obtain a solid product; the solid product is slurried with an ethyl acetate-n-hexane mixed solvent, and then filtered to obtain a compound having a structure shown in Formula II; the volume ratio of ethyl acetate to n-hexane in the ethyl acetate-n-hexane mixed solvent is preferably 1:3, and the slurrying time is preferably 2h.

[0060] After obtaining the compound having the structure shown in Formula II, the present invention mixes the compound having the structure shown in Formula II, a metal catalyst and a solvent for hydrogenolysis reaction to obtain 6-chloro-2,3-diaminotoluene and 9,10-dihydrophenanthrene. In the present invention, the metal catalyst is preferably one or more of Rh / C, Pd / C, Pt / C, Raney nickel and Raney cobalt, more preferably Pt / C, and the mass fraction of Pt in the Pt / C is preferably 5%; the mass of the metal catalyst is preferably 2% to 30% of the mass of the compound having the structure shown in Formula II, more preferably 5% to 10%.

[0061] In the present invention, the solvent for the hydrogenolysis reaction is preferably one or more of water, dichloromethane, furan solvents, 1,4-dioxane and alcohol solvents; the alcohol solvent is preferably methanol or ethanol, and the furan solvent is preferably tetrahydrofuran or 2-methyltetrahydrofuran; in a specific embodiment of the present invention, the solvent for the hydrogenolysis reaction is preferably methanol or ethanol. The present invention has no special requirements for the amount of the solvent, as long as the hydrogenolysis reaction can proceed smoothly.

[0062] In the present invention, the hydrogen pressure of the hydrogenolysis reaction is preferably 0.2-1 MPa, more preferably 0.6-0.8 MPa, the temperature of the hydrogenolysis reaction is preferably 0-80°C, more preferably 30-50°C, and the time of the hydrogenolysis reaction is preferably 5-15h; in a specific embodiment of the present invention, it is preferred to confirm whether the hydrogenolysis reaction is completed by a point plate; the hydrogenolysis reaction is preferably carried out in an autoclave.

[0063] In a specific embodiment of the present invention, it is preferred to first add the solvent into the autoclave, add the compound having the structure shown in Formula II and the metal catalyst under stirring conditions, then close the autoclave, replace the autoclave with nitrogen, and then replace the nitrogen with hydrogen after the nitrogen replacement is completed, and adjust the hydrogen pressure to the above range for hydrogenolysis reaction.

[0064] After the hydrogenolysis reaction is completed, the present invention preferably filters the obtained product liquid, and the filter residue is a metal catalyst, and the metal catalyst is reused; the obtained filtrate is spun at 35-45° C. until no solvent flows out, and the remaining solution is a solution of 6-chloro-2,3-diaminotoluene dissolved in 9,10-dihydrophenanthrene; the remaining solution is distilled under reduced pressure at 190-210° C., and the distilled product is 9,10-dihydrophenanthrene; the remaining solid product after the reduced pressure distillation is pulped with a methanol-water mixed solvent, and then filtered to obtain 6-chloro-2,3-diaminotoluene; the volume ratio of methanol to water in the methanol-water mixed solvent is preferably 4:21; the pulping time is preferably 2 hours.

[0065] The present invention also provides an intermediate for synthesizing 6-chloro-2,3-diaminotoluene, which has a structure shown in Formula II:

[0066]

[0067] In formula II, R is C 1-4 Alkyl or benzyl.

[0068] The preparation method of the intermediate represented by formula II is consistent with the above scheme and will not be repeated here.

[0069] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0070] Example 1 Preparation of the compound of formula I

[0071]

[0072] Phenanthrenequinone (350 g), methoxyamine hydrochloride (336.7 g), NaOAc (606 g) and methanol (3500 mL) were added to a reactor, heated to 60-65°C and refluxed for 5 h. After the reaction, the solvent was evaporated, slurried twice with 1000 mL of water each time, and then filtered, and the filter cake was rinsed with water to obtain 438.3 g of a light yellow solid dimethylbisoxime compound with a yield of 98.1% and a purity of 99.5%.

[0073] Example 2 Preparation of the compound of formula I

[0074]

[0075] Phenanthrenequinone (350 g), ethoxylated amine hydrochloride (390.0 g), NaOAc (606 g) and ethanol (3500 mL) were added to a reactor, heated to 60-70°C and refluxed for 8 h. After the reaction, the solvent was evaporated, slurried twice with 1000 mL of water each time, and then filtered, and the filter cake was rinsed with water to obtain 478.7 g of a pale yellow solid bisethylbisoxime compound, with a yield of 96.9% and a purity of 99.4%.

[0076] Example 3 Preparation of the compound of formula II

[0077]

[0078] Under nitrogen protection, add 2,6-dichlorotoluene (78g) and 200mL tetrahydrofuran to the dry reactor, cool the low-temperature constant temperature reaction bath to -30~-20℃, add 275mL of freshly prepared lithium diisopropylamide (2.0M tetrahydrofuran solution) and stir for 1h. Dissolve 120g of the dimethylbisoxime compound obtained in Example 1 in 260mL tetrahydrofuran to form a solution, keep it warm at -30±5℃ and slowly drop it into the 6-chloro-2,3-diaminotoluene reaction solution, continue to keep it warm and stir for 3h after dropping, then slowly rise to 0℃ and continue to react for 8h. After the reaction is completed, add 300mL of saturated NH4Cl solution to quench the reaction, and add ethyl acetate to extract (800mL each time, 3 times). The organic phases were combined and dried by rotation, and 300 mL of ethyl acetate-n-hexane mixed solvent (the volume ratio of ethyl acetate to n-hexane was 1:3) was added and slurried for 2 h. 145.8 g of a brown-yellow solid dimethyl-substituted compound of formula II was obtained by filtration with a yield of 81.2% and a purity of 99.1%.

[0079] Example 4 Preparation of the compound of formula II

[0080]

[0081] Under nitrogen protection, add 2,6-dichlorotoluene (78g) and 200mL tetrahydrofuran to the dry reactor, cool the low-temperature constant temperature reaction bath to -50±5℃, add 275mL of freshly prepared sec-butyl lithium (2.0M tetrahydrofuran solution) and stir for 1h. Implementation: 132g of the diethylbisoxime compound obtained in Example 2 was dissolved in 260mL tetrahydrofuran to form a solution, and the solution was slowly dripped into the 6-chloro-2,3-diaminotoluene reaction solution at -50±5℃. After the dripping, the reaction was continued to be stirred for 5h, and then slowly raised to 0℃ and continued to react for 10h. After the reaction was completed, a saturated NH4CI solution (300mL) was dripped into the layer and extracted with ethyl acetate (800mL each time, 3 times). The organic phases were combined, a saturated sodium chloride solution (500mL) was added to wash the organic layer, and the organic layer was concentrated under reduced pressure. The residue was added with 300 mL of ethyl acetate-n-hexane mixed solvent (the volume ratio of ethyl acetate to n-hexane was 1:3) and slurried for 2 h. The brown solid diethyl substituted compound of formula II was obtained by filtration with a yield of 76.6% and a purity of 99.3%.

[0082] Example 5 Synthesis of 6-chloro-2,3-diaminotoluene and 9,10-dihydrophenanthrene

[0083]

[0084] 500mL of methanol was added to the autoclave, and 100g of the dimethylbisoxime compound of formula II obtained in Example 3 and 5g of a Pt / C catalyst with a Pt content of 5% were added under stirring. The autoclave was closed, and the air in the autoclave was replaced with nitrogen three times. After the nitrogen replacement was completed, it was replaced with hydrogen three times. The hydrogen pressure was controlled to be 0.6-0.7MPa, the temperature was raised to 55±5°C and the reaction was kept warm for 8h. After the plate was confirmed to be completed, the filter was filtered and the filter residue was Pt / C and could be reused. The filtrate was decompressed and rotated to no dripping at a water bath temperature of 40±5°C, and a brown and black solution was obtained, which was a solution of 6-chloro-2,3-diaminotoluene dissolved in 9,10-dihydrophenanthrene. The temperature was continued to rise to 200±10°C, and 9,10-dihydrophenanthrene was distilled out under reduced pressure as a colorless liquid of 44.0 grams, with a yield of 95.6% and a purity of 99.6%. After cooling to room temperature, 80 mL of methanol and 420 mL of water were added to the kettle and slurried for 2 h. 37.6 g of brown solid was obtained by filtration, which was 6-chloro-2,3-diaminotoluene with a yield of 91.3% and a purity of 99.8%.

[0085] The H NMR spectrum of chloro-2,3-diaminotoluene is as follows Figure 1 The hydrogen spectrum data are as follows: 1 H NMR (400MHz, CDCl3) δ6.74(d,1H),6.53(d,1H),3.56(s,4H),2.25(s,3H); LC-MS(EI)m / z:156.1(M + );

[0086] The H NMR spectrum of 9,10-dihydrophenanthrene is as follows Figure 2 The hydrogen spectrum data are as follows: 1 H NMR (400MHz, CDCl3): δ7.90 (d, 2H), 7.50-7.41 (m, 2H), 7.36-7.28 (m, 4H), 3.01 (s, 4H). GC-MS (EI) m / z: 180.1 (M + ).

[0087] Example 6 Synthesis of 6-chloro-2,3-diaminotoluene and 9,10-dihydrophenanthrene

[0088]

[0089] 500mL of ethanol was added to the autoclave, and 100g of the diethylbisoxime compound of formula II obtained in Example 4 and 10g of a Pt / C catalyst having a Pt content of 5% were added under stirring. The autoclave was closed, and the air in the autoclave was replaced with nitrogen three times. After the nitrogen replacement was completed, it was replaced with hydrogen three times. The hydrogen pressure was controlled to be 0.7-0.8MPa, and when the temperature was raised to 60±5°C and the reaction was kept warm for 5h, the plate was confirmed to be completed and filtered, and the filter residue was Pt / C and could be reused. The filtrate was decompressed and rotated to no dripping at a water bath temperature of 40±5°C, and a brown and black solution was obtained, which was a solution of 6-chloro-2,3-diaminotoluene dissolved in 9,10-dihydrophenanthrene. The temperature was continued to rise to 200±10°C, and 9,10-dihydrophenanthrene was distilled out under reduced pressure as a colorless liquid of 40.1g, with a yield of 93.4% and a purity of 99.5%. After cooling to room temperature, 80 mL of methanol and 420 mL of water were added to the kettle and slurried for 2 h. 34.4 g of brown solid was obtained by filtration, which was 6-chloro-2,3-diaminotoluene with a yield of 89.5% and a purity of 99.6%.

[0090] The products chloro-2,3-diaminotoluene and 9,10-dihydrophenanthrene were tested by hydrogen nuclear magnetic resonance spectroscopy, and the results showed that the obtained products had the target structure.

[0091] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing 6-chloro-2,3-diaminotoluene, characterized in that: The following steps are involved: (1) Under the action of a first alkaline reagent, phenanthrenequinone and an alkoxyamine or an alkoxyamine salt are subjected to an oxime etherification reaction in a solvent to obtain a phenanthrenequinone bisoxime ether structure compound; the alkoxyamine is an alkoxyamine or a benzyloxyamine; the number of carbon atoms in the alkoxyamine is 1 to 4; the phenanthrenequinone bisoxime ether structure compound has a structural formula as shown in Formula I: In formula I: R is C 1-4 Alkyl or benzyl; (2) Under the action of a second alkaline reagent, the phenanthrenequinone bisoxime ether structure compound is subjected to a cycloaddition reaction with 2,6-dichlorotoluene in a solvent to obtain a compound having a structure shown in Formula II; In formula II: R is C 1-4 Alkyl or benzyl; (3) Mixing the compound having the structure shown in Formula II, a metal catalyst and a solvent for hydrogenolysis reaction to obtain 6-chloro-2,3-diaminotoluene and 9,10-dihydrophenanthrene.

2. The preparation method according to claim 1, characterized in that: The first alkaline agent is sodium acetate; the molar ratio of the phenanthrenequinone to the first alkaline agent is 1:4-8; The molar ratio of phenanthrenequinone to alkoxyamine or alkoxyamine salt is 1:2-4; The solvent for the oxime etherification reaction is one or more of water, alcohol solvents, furan solvents and dimethyl sulfoxide.

3. The preparation method according to claim 1, characterized in that: The temperature of the oxime etherification reaction is 10-70° C. and the time is 2-12 hours.

4. The preparation method according to claim 1, characterized in that: The molar ratio of the phenanthrenequinone bisoxime ether structure compound to 2,6-dichlorotoluene is 1:1-5; The second alkaline agent is one or more of n-butyl lithium, sec-butyl lithium, tert-butyl lithium, lithium diisopropylamide, potassium amide, sodium amide and sodium bis(trimethylsilyl)amide; the molar ratio of the phenanthrenequinone bisoxime ether structure compound to the second alkaline agent is 1:1-4; The solvent for the cycloaddition reaction is one or more of toluene, acetonitrile, diethyl ether, 1,4-dioxane, dichloromethane and tetrahydrofuran.

5. The preparation method according to claim 1, characterized in that: The temperature of the cycloaddition reaction is -100 to 0°C, and the reaction time is 6 to 18 hours.

6. The preparation method according to claim 1, characterized in that: The metal catalyst is one or more of Rh / C, Pd / C, Pt / C, Raney nickel and Raney cobalt; the mass of the metal catalyst is 2% to 30% of the mass of the compound having the structure shown in Formula II.

7. The preparation method according to claim 1, characterized in that: The solvent for the hydrogenolysis reaction is one or more of water, dichloromethane, furan solvents, 1,4-dioxane and alcohol solvents.

8. The preparation method according to claim 1, characterized in that: The hydrogen pressure of the hydrogenolysis reaction is 0.2-1 MPa, the reaction temperature is 0-80° C., and the reaction time is 5-15 hours.

9. An intermediate for synthesizing 6-chloro-2,3-diaminotoluene, characterized in that: It has the structure shown in formula II: In formula II, R is C 1-4 Alkyl or benzyl.

10. The method for preparing the intermediate according to claim 9, characterized in that: The following steps are involved: Carry out the reaction according to the method described in steps (1) to (2) of claim 1 to obtain the intermediate.

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