CN114703492A - Dasotriprin electrochemical preparation method - Google Patents

Dasotriprin electrochemical preparation method Download PDF

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CN114703492A
CN114703492A CN202210373506.1A CN202210373506A CN114703492A CN 114703492 A CN114703492 A CN 114703492A CN 202210373506 A CN202210373506 A CN 202210373506A CN 114703492 A CN114703492 A CN 114703492A
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naphthylamine
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胡艾希
刘宇阳
王曼
叶姣
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Hunan University
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Abstract

The invention relates to an electroreduction preparation method of 1,2,3, 4-tetrahydro-1-naphthylamine compounds (I) and hydrochlorides thereof, which is characterized in that in an alkaline solution, 3, 4-dihydronaphthalene-1 (2H) -ketoxime compounds (II) are prepared into the 1,2,3, 4-tetrahydro-1-naphthylamine compounds (I) by an electroreduction method; the preparation reaction is as follows:

Description

Daxotriptyline electrochemical preparation method
Technical Field
The invention relates to a novel method for preparing Dasotroparin by electro-reduction, in particular to a method for preparing 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthylamine compounds and hydrochlorides thereof by electro-reduction of 4- (3, 4-dichlorophenyl) -3, 4-dihydronaphthalene-1 (2H) -ketoxime compounds.
Background
In 2007, Alain et al [ Iap bir domain binding compounds, WO 2007104162A1,2007.09.20] report that a compound 2 containing a1,2, 3, 4-tetrahydro-1-naphthylamine structure has a promoting effect on Smas apoptosis, and the biological activity and clinical research of the compound is ongoing; compound 2 was prepared in 2007 by James et al [ Bir domain binding compounds, WO2007101347,2007.9.13] selecting (R) -1,2,3, 4-tetrahydronaphthalenyl-1-amine, with a total yield of 57%. The specific synthetic route is as follows:
Figure BDA0003589759360000011
elise et al [ Benzylamide derivatives as cannabinoid receptors of inverse agonists, WO2007064272A1,2007.06.07] report that N- (1,2,3, 4-tetrahydronaphthalen-1-yl) thiourea (3) has a good therapeutic effect on obesity; bhandari et al [ Synthesis of tetrahydrophenyl thioureas as potential antipestite supply, bioorganic & Medicinal Chemistry,2004,12(15): 4189-; selecting 10% KOH to react in ethanol for deprotection to obtain N- (1,2,3, 4-tetrahydronaphthalene-1-yl) thiourea 3.
Figure BDA0003589759360000012
Tangallapally et al [ Synthesis and Evaluation of nitrofurylamides as Novel Antituberculosis, Agents.J.Med.chem.2004, 47:5276-5283 ] reported that Compound 4 had good antitubercular effect. Tangallcalaly et al [ Synthesis of tetrahydrophenyl thioureas as phosphate salts, J.Med.chem.,2004,47(21):5276-5283 ] described the activation of 5-nitro-2-furancarboxylic acid and 1-amino-1, 2,3, 4-tetrahydronaphthalene in DMF using 98% EDCI and N, N-Dimethylaminopyridine (DMAP) for 14h at 25 ℃ to give compound 4.
Figure BDA0003589759360000021
In 2007 Elise et al [ Benzylamide derivatives as cannabinoid receptor antagonists or invertase agonists, WO2007064272A1,2007.06.07] reported that 1,2,3, 4-tetrahydro-1-naphthylamine derivative 5 receptor was used as cannabinoid CB1 receptor antagonist for clinical study of anti-obesity.
Figure BDA0003589759360000022
Zhang in 2012 et al [ 1-amino-1, 2,3, 4-tetrahydronaphthalene resolution and racemization method, CN102675123A,2012.9.19] select 3, 4-dihydro-1- (2H) -naphthalenone oxime to be reduced into racemic 1,2,3, 4-tetrahydro-1-naphthylamine by Pd/C, and the yield is 96%.
Figure BDA0003589759360000023
Gutman et al [ Stereo-and regioselectivity in asymmetric synthesis of α -amino substistuted benzene cyclic compounds: Asymmetry,1998,9(24):4369-4379] selected 3, 4-dihydronaphthalen-1 (2H) -one to react with (S) -1-phenylethane-1-amine to give intermediate 6, which was isomerized to intermediate 7 at-30 ℃ and reduced to give (R) -1,2,3, 4-tetrahydro-1-naphthylamine by Pd/C.
Figure BDA0003589759360000024
(R) -N-acetyl-1-phenyl-ethylamine is obtained by catalytic hydrogenation of 3, 4-dihydronaphthalene-1 (2H) -ketoxime with Pd/C lipase in 2005 Kingwan column et al [ method for preparing chiral amine, CN1633427A,2005.6.29], and (R) -1,2,3, 4-tetrahydro-1-naphthylamine is obtained by refluxing in 1.2N HCl for 9H, with the yield of 70% and 97% ee.
Figure BDA0003589759360000025
In 2001 Takei et al [ Ruthenium-catalyzed enzymological hydrolysis of ketoximes using cardiac oxydazolylchlorins, chem. Commun, 2001, (22):2360-]Selecting 12,3, 4-tetralone oxime, carrying out asymmetric hydrosilylation on a chiral ruthenium complex (8), and carrying out acid hydrolysis to obtain correspondingly selective (R) -1,2,3, 4-tetrahydro-1-naphthylamine; hand (W.E.)Ruthenium complex (8): RuCl2(PPh3) (oxazolinyl ferrocenyl phosphine); the yield was 71%, 79% ee.
Figure BDA0003589759360000031
Lei et al [ Synthesis of α -Deutered Primary Amines via reducing depletion of oxides Using D in 20212O as a Deuterium Source,J.Org.Chem.,2021,86(3):2907-2916.]Selecting 12,3, 4-tetrahydronaphthalene ketoxime, selecting heavy water and raw materials with the mass ratio of 1: 4.97 under the protection of argon, adding 10mL of tetrahydrofuran solution of samarium diiodide with the concentration of 0.1mol/L, violently stirring at room temperature for 15 minutes, adding the crude product into cyclopentyl methyl ether hydrochloride solution to obtain 1-deuterated-2, 3, 4-trihydro-1-naphthylamine hydrochloride with the yield of 98 percent and the deuteration rate of 95 percent.
Figure BDA0003589759360000032
Pakulski et al [ endogenous selective reduction of ketone ethers with bond-oxazaborolidines and synthesis of the key interfacial leading to (S) -rivastigmine, Tetrahedron: asymmetry.2012,23(9):716 721 ] selecting 12,3, 4-tetrahydronaphthalene ketoxime, first etherifying the benzyl group, selecting a molar ratio of benzyl ether to catalyst to borane/THF of 1: 1.25: 7.5, reacting for 48h, and acidifying in hydrochloric acid for 24h to obtain 1,2,3, 4-tetrahydro-1-naphthylamine with a yield of 70%.
Figure BDA0003589759360000033
Chengpeng et al (synthesis of monoamine oxidase inhibitor 1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride, university of Chongqing university of medicine, 2013.38(6): 580. Bufonic acid 582.) select benzene to prepare 1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride through acylation, reduction, cyclization, condensation, reduction and salt formation, with the total yield of 43.6%; the yield of the reduction reaction was 82%.
Figure BDA0003589759360000034
In 2005, river et al [ facility retrieval of O-sized oxides on Reduction with Boron Trifluoride/Borane, J.Org.chem.,2005,70(24): 10132-.]Selection of 1,2,3, 4-tetrahydronaphthalene silylated oximes via BH3The reduction reaction is carried out for 1h at the temperature of 55 ℃, and the 1,2,3, 4-tetrahydro-1-naphthylamine is obtained with the yield of 33 percent.
Figure BDA0003589759360000035
Welch et al [ anti pressants derivatives of cis-4-phenyl-1,2,3, 4-tetrahydrogen-1-naphthalene-amine, U.S. Pat. No. 3, 4536518A,1985.8.20] selected (S) -phenyl (((S) -1,2,3, 4-tetrahydronaphthalen-1-yl) amino) methanol (9) and debenzylated with hydrochloric acid to give (S) -1,2,3, 4-tetrahydro-1-naphthylamine in 1985.
Figure BDA0003589759360000041
The preparation of [ (R) -alpha-tetrahydronaphthalene, 2008,16(15):28-29. before the development, 2008,16(15) ] of Kyong et al selects 3, 4-dihydronaphthalene-1 (2H) -ketone to react with hydroxylamine hydrochloride to obtain 3, 4-dihydronaphthalene-1 (2H) -ketoxime, and the latter is reduced and refluxed for 1H by using metallic sodium to obtain 1,2,3, 4-tetrahydro-1-naphthylamine with the yield of 98%.
Figure BDA0003589759360000042
On day 14/5/2020, the U.S. Food and Drug Administration (FDA) has accepted New Drug Application (NDA) for the treatment of moderate to severe Binge Eating Disorder (BED) with dasotraline (10, dasotraline); chemical name: (1R,4S)4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthalenamine (10).
Figure BDA0003589759360000043
The application of 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthylamine in treating cancer, CN101222917A,2008.7.16, in the invention patent of china in 2008 describes that 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthylamine and isomers thereof have antiproliferative activity on thirty tumor cells such as lung cancer, breast cancer and the like. The chinese invention patent in 2009 [ treatment of CNS disorders with trans 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthalenamine and its carboxamide, CN101712626B,2013.11.20] describes that (1R,4S) -4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthalenamine and (1S,4R) -4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthalenamine can be used for the treatment of Central Nervous System (CNS) disorders mediated by monoamine activity.
Dukang et al [ Synthesis of 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthalenamine Using the Salcatel reaction, J.Chem.Chem.China, 2000,9(6): 394-: 4- (3, 4-dichlorophenyl) -3, 4-dihydronaphthalene-1 (2H) -ketone reacts for 4H at 180 ℃ under the action of formamide and formic acid, and the yield is 60%.
Figure BDA0003589759360000044
In 2021, European and solar terms and the like [ a sertraline side chain amino structure derivative and a preparation method and application thereof, CN112661657,2021.04.16] selects 4- (3, 4-dichlorophenyl) -3, 4-dihydronaphthalene-1 (2H) -ketone as a starting material, reacts with ammonium acetate in isopropanol at the temperature of 80 ℃ for 2H, and is reduced by sodium borohydride for 16H to obtain 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthylamine.
Figure BDA0003589759360000051
Fabrice et al [ Processes for preparing demethylation sertraline or a pharmacological acceptable salt of, WO2008065177A1,2008.6.5] selects 4- (3, 4-dichlorophenyl) -3, 4-dihydro-1-naphthalenone to perform imidization on p-methoxybenzylamine to obtain (1S,4S) -and (1R,4R) -cis isomers of benzylated amine, and uses (+) -tartaric acid to perform resolution and debenzylation to obtain the (+) -tartrate demethyl sertraline, wherein the total yield is lower than 3%.
Figure BDA0003589759360000052
Zhao et al (preparation of chiral amides and amines, CN103588659A, 2014.02.19) in 2014]4- (3, 4-dichlorophenyl) -3, 4-dihydronaphthalene-1 (2H) -ketoxime (11) is selected to be acylated in situ to obtain an intermediate (12), acylated enamide (13) and diacylate (14) are obtained through reduction and acylation, the mixture is treated by sodium hydroxide, and hydrogen sulfate/tetrabutylammonium hydroxide is used as a phase transfer agent to convert the intermediate (14) into the enamide (13). Alenamide (13) in isopropanol, (R, R) -MeBPE (COD) RhBF4Introducing hydrogen (90psig) under catalysis, and carrying out hydrogenation reaction for 7.5h to obtain an intermediate (15); trans acetamide (15) was refluxed for 48h in propanol-hydrochloric acid and deacetylated to give ammonium hydrochloride salt (16) in 80% yield.
Figure BDA0003589759360000053
Waltham et al, Enamide Process, US20180215702A1,2018.8.2, 2018]Selecting (S) -4- (3, 4-dichlorophenyl) -3, 4-dihydronaphthalene-1 (2H) -ketone and hydroxylamine hydrochloride to generate intermediate ketoxime (11) under the protection of nitrogen, obtaining O-acetyl oxime intermediate (12) through in-situ acylation, and then isomerizing to obtain enamide (13) with the yield of 89%. Adding the enamide (13) to isopropanol, adding (R, R) -MeBPE (COD) RhBF4Hydrogenation was carried out with hydrogen (90psig) to give (1R,4S) -acetamide intermediate (15) in 83% yield. (1R,4S) -acetamide (15) was deacetylated with oxalyl chloride in dry THF to give compound 10 in 86% yield.
Figure BDA0003589759360000061
In 2021 Roberto et al [ Preparation of amide intermediates for the synthesis of daisolidine, EP3800178A1,2021.4.7](S) -4- (3, 4-dichlorophenyl) -3, 4-dihydro-1-naphthalenone with NH is described3Adding 2 times of equivalent of Ti (OiPr) into the methanol solution at 0 DEG C4Reacting for 48 hours after the temperature is raised to 20 ℃, cooling, adding triethylamine and acetic anhydride, and reacting for 24 hours to obtain N- ((S) -4- (3, 4-dichlorophenyl) -3, 4-dihydronaphthalene-1-yl) acetamide (13), wherein the yield is 85.6%; then (R, R) -Norphos (COD) Rh-BF4Hydrogenation to give N- ((1R,4S) -4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydronaphthalen-1-yl) acetamide (15) in 91.5% yield; (1R,4S) -4- (3, 4-dichlorophenyl) -1,2,3,4 tetrahydro-1-naphthylamine hydrochloride (16) was obtained by reacting with concentrated hydrochloric acid in isopropanol with a yield of 83.3%.
Figure BDA0003589759360000062
Disclosure of Invention
The technical problem to be solved by the invention is to provide an electroreduction preparation method of 1,2,3, 4-tetrahydro-1-naphthylamine compound (I) and hydrochloride thereof; to overcome the problems of the classical reduction reaction.
In order to solve the technical problem, the invention provides the following technical scheme:
the technical scheme of the invention provides an electroreduction preparation method of 1,2,3, 4-tetrahydro-1-naphthylamine compound (I) and hydrochloride thereof, which is characterized in that in an alkali solution, the 3, 4-dihydronaphthalene-1 (2H) -ketoxime compound (A) is prepared into the 1,2,3, 4-tetrahydro-1-naphthylamine compound (I) by an electroreduction method; the preparation reaction is as follows:
Figure BDA0003589759360000071
in a separated electrolytic cell, an alkaline solution of the 3, 4-dihydronaphthalene-1 (2H) -ketoxime compound (A) and an organic solvent form a catholyte; the anolyte is alkaline solution; obtaining a cathode electrolysis product of the 1,2,3, 4-tetrahydro-1-naphthylamine compound (I) through an electro-reduction reaction; and (3) carrying out post-treatment on the cathode electrolysis product to obtain the 1,2,3, 4-tetrahydro-1-naphthylamine compound, and introducing HCl gas into the compound to form salt to obtain 1,2,3, 4-tetrahydro-1-naphthylamine compound hydrochloride.
Relative to a referenceThe voltage of the working electrode of the cathode is 1.0V-3.0V; the current density of the cathode working electrode is 0.4A/cm2～1.2A/cm2To (c) to (d); the current is between 0.4 and 1.2A, and the electrolysis temperature is between 25 and 85 ℃.
The concentration of the 3, 4-dihydronaphthalene-1 (2H) -ketoxime compound (A) is between 5.0g/L and 20.0 g/L;
the alkali liquor is selected from: potassium hydroxide solution or sodium hydroxide solution;
selecting alkali liquor concentration: 0.1 mol/L-5 mol/L; preferably: 0.1mol/L, 0.2mol/L, 0.5mol/L, 1mol/L, 2mol/L, 3mol/L or 5 mol/L;
the reference electrode of the divided electrolytic cell is: a saturated potassium chloride calomel electrode or an Ag/AgCl electrode.
The cathode of the separated electrolytic cell is as follows: brass electrodes, red copper electrodes, zinc sheets, nickel, lead or platinum electrodes;
the anode of the separated electrolytic cell is as follows: a platinum mesh electrode, a platinum sheet electrode, or a graphite electrode;
the diaphragm of the separated electrolytic cell is as follows: HF-101 strong acid cation exchange membrane or N-117 proton membrane;
the organic solvent in the catholyte is selected from: any one or more of acetonitrile, butyronitrile, methanol, ethanol, tetrahydrofuran or N, N dimethylformamide;
the volume ratio of the organic solvent to the alkali liquor in the catholyte is selected from: 1: 1 to 1: 10.
The cis-trans four isomers (Ib) can be separated into cis-two isomers and trans-two isomers by adopting a recrystallization method, and the obtained two trans-enantiomers are resolved by chiral organic acid such as chiral tartaric acid or chiral mandelic acid to obtain (1R,4S) -4- (3, 4-dichlorophenyl) -1,2,3,4 tetrahydro-1-naphthylamine (Dasosenlin, 10). The two cis enantiomers are resolved by chiral organic acid such as chiral tartaric acid or chiral mandelic acid to obtain (1S,4S) -4- (3, 4-dichlorophenyl) -1,2,3,4 tetrahydro-1-naphthylamine (17). Methylation of compound 17 gave (1S,4S) -4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-N-methyl-1-naphthalenamine (sertraline, 18):
Figure BDA0003589759360000072
the beneficial technical effects are as follows:
the invention relates to an electroreduction preparation method of Dasotroparin, which is an electroreduction preparation method of 1,2,3, 4-tetrahydro-1-naphthylamine compounds (I) and hydrochlorides thereof, and has the following advantages:
(1) no toxic or dangerous reducing agent is needed in the reduction reaction, and the 'electron' is a clean reaction reagent and is an important component for developing the 'green pharmaceutical industry'.
(2) In the process of electro-reduction, a high-purity and high-yield intermediate can be obtained only in an alkaline solution without adding a catalyst additionally.
(3) In industrial production, the process flow is simplified, the production cost is reduced, and the method is safe and environment-friendly and is suitable for large-scale popularization and application.
Toxic or dangerous reducing agents are not needed in the electro-reduction reaction, and the method is an important component for developing the green pharmaceutical industry; the intermediate with high purity and high yield can be obtained in an alkali solution without adding a catalyst.
The electro-reduction preparation method of the 1,2,3, 4-tetrahydro-1-naphthylamine compound (I) and the hydrochloride thereof simplifies the process flow and reduces the production cost in the industrial production of the dacoqulin, basically has no pollution to the environment, and is suitable for large-scale popularization and application.
Figure BDA0003589759360000081
Drawings
FIG. 1 is a schematic structural view of a divided electrolytic cell
Detailed Description
The following examples are intended to illustrate the invention without further limiting it.
Example 1
Electro-reduction preparation of 1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride
Figure BDA0003589759360000082
Installing a separated electrolytic cell, and selecting an N-117 proton membrane and a saturated potassium chloride calomel electrode reference electrode; adding 0.32g (1.99mmol) of 3, 4-dihydronaphthalene-1 (2H) -ketoxime into the cathode chamber, dissolving the substrate by using 5mL of methanol, and adding 40mL of 0.2mol/L KOH solution as electrolyte; 45mL of 5mol/L KOH solution was added to the anode compartment as an electrolyte. The cathode electrode was a zinc plate (2X 2 cm)2) The anode electrode is a platinum sheet (1X 1 cm)2) The cell voltage is 8.5V, the current is 0.6A, the working potential is about 2.2V, the temperature is kept at 50 ℃, and the electrolysis is carried out for 4 hours. Removing the methanol solvent by performing rotary evaporation on catholyte, extracting the residual alkaline aqueous solution with ethyl acetate for 2 times, adjusting the pH value to 8-9 with dilute hydrochloric acid solution, extracting for 2 times, combining the extract liquor, and adding anhydrous Na2SO4Drying and desolventizing to obtain a light yellow white oily compound, adding 3mL of diethyl ether for dilution and dissolution, introducing HCl gas to generate a white solid (1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride), carrying out rotary evaporation on the solvent to obtain a white solid, washing with ethyl acetate, and drying a filter cake to obtain white solid powder-0.341 g of 1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride, wherein the yield is 93.2%.1H NMR(400MHz，DMSO-d6)δ：8.62(s，3H，NH3 +) 7.65-7.15 (m, 4H, benzene ring), 4.40(s, 1H, CH), 2.85-2.65 (m, 2H, 4-CH)2)，2.15～1.65(m，4H，2,3-CH2CH2)。
Example 2
Preparation of 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride
Figure BDA0003589759360000091
Installing a separate electrolytic cell, and selecting an N-117 proton membrane and a saturated potassium chloride calomel electrode reference electrode; adding 0.31g (1.00mmol) of 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydronaphthalene-1-ketoxime into the cathode chamber, dissolving the substrate by using 15mL of ethanol, and adding 30mL of 0.2mol/L KOH solution as electrolyte; 45mL of 5mol/L KOH solution was added to the anode compartment as an electrolyte. Cathode electrodeIs a zinc sheet (2 x 2 cm)2) The anode electrode is a platinum sheet (1 multiplied by 1 cm)2) The cell voltage is 14V, the current is 0.6A, the working potential is about 2.1V, the constant temperature is 50 ℃, and the electrolysis is carried out for 7 h. Extracting the catholyte with ethyl acetate for 2 times, adjusting pH to 8-9 with dilute hydrochloric acid solution, extracting for 2 times, mixing extractive solutions, and adding anhydrous Na2SO4Drying, desolventizing to obtain light yellow oily compound, diluting with 5mL diethyl ether, dissolving, introducing HCl gas to obtain white solid [4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride]The solvent is evaporated by rotation to obtain white solid, the white solid is washed by ethyl acetate, and a filter cake is dried to obtain white solid powder, namely 0.310g of 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride, with the yield of 94.2%.1H NMR(400MHz，DMSO-d6)δ：8.75(s，3H，NH3 +) 7.80-6.70 (m, 7H, benzene ring), 4.65-4.45 (m, 1H, 4-CH), 4.35-4.05 (m, 1H, 1-CH), 2.35-1.75 (m, 4H, CH)2CH2)。
Example 3
Preparation of 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride
Figure BDA0003589759360000092
Installing a separated electrolytic cell, and selecting an N-117 proton membrane and a saturated potassium chloride calomel electrode reference electrode; adding 0.31g (1.00mmol) of 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydronaphthalene-1-ketoxime into the cathode chamber, dissolving the substrate by using 15mL of ethanol, and adding 30mL of 0.2mol/L KOH solution as electrolyte; 45mL of 5mol/L KOH solution was added to the anode compartment as an electrolyte. The cathode electrode was a zinc plate (2X 2 cm)2) The anode electrode is a platinum sheet (1 multiplied by 1 cm)2) The cell voltage is 14V, the current is 0.8A, the working potential is about 2.1V, the constant temperature is 50 ℃, and the electrolysis is carried out for 7 h. Extracting the catholyte with ethyl acetate for 2 times, adjusting pH to 8-9 with dilute hydrochloric acid solution, extracting for 2 times, mixing extractive solutions, and adding anhydrous Na2SO4Drying, desolventizing to obtain light yellow oily compound, diluting with 5mL diethyl ether, dissolving, introducing HCl gas to obtain white solid [4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride]Steaming in a rotating mannerSolvent to obtain white solid, washing with ethyl acetate, drying filter cake to obtain white solid powder-0.320 g of 4- (3, 4-dichlorophenyl) -1,2,3, 4-tetrahydro-1-naphthylamine hydrochloride, yield 97.3%.1H NMR(400MHz，DMSO-d6)δ：8.75(s，3H，NH3 +) 7.80 to 6.70(m, 7H, benzene ring), 4.65 to 4.45(m, 1H, 4-CH), 4.35 to 4.05(m, 1H, 1-CH), 2.35 to 1.75(m, 4H, CH)2CH2)。
In the present specification, the invention has been described with reference to specific embodiments thereof. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.

Claims (8)

1. A method for preparing 1,2,3, 4-tetrahydro-1-naphthylamine compounds shown in formula I by electro-reduction is characterized in that 3, 4-dihydronaphthalene-1 (2H) -ketoxime compounds shown in formula A are prepared into 1,2,3, 4-tetrahydro-1-naphthylamine compounds in an alkali solution by the electro-reduction method; the preparation reaction is as follows:
Figure FDA0003589759350000011
Y＝H(Ⅰa),3,4-Cl2C6H3(Ⅰb)
in a separated electrolytic cell, an alkaline solution of a 3, 4-dihydronaphthalene-1 (2H) -ketoxime compound shown in a formula A and an organic solvent form a catholyte; the anolyte is alkaline solution; obtaining a cathode electrolysis product of the 1,2,3, 4-tetrahydro-1-naphthylamine compound through an electro-reduction reaction; the cathodic electrolysis product is post-treated to obtain 1,2,3, 4-tetrahydro-1-naphthylamine compounds, and HCl gas is introduced into the compound to form salt so as to obtain 1,2,3, 4-tetrahydro-1-naphthylamine compound hydrochloride;
the voltage of the cathode working electrode is 1.0V-3.0V relative to the reference electrode; the current density of the cathode working electrode is selected from: 0.4A/cm2～1.2A/cm2(ii) a The current is selected from: 0.4-1.2A, and the electrolysis temperature is selected from the following: 25-85 ℃;
the alkaline solution is selected from: sodium hydroxide solution or potassium hydroxide solution; the reference electrode of the diaphragm cell is selected from: a saturated potassium chloride calomel electrode or an Ag/AgCl electrode.
2. The process for the electroreductive preparation of 1,2,3, 4-tetrahydro-1-naphthylamine compounds according to claim 1, wherein the cathode of the divided cell is selected from the group consisting of: brass electrodes, copper electrodes, zinc sheet, nickel, lead or platinum electrodes.
3. The process for the electroreductive preparation of 1,2,3, 4-tetrahydro-1-naphthylamine compounds according to claim 1, wherein the anode of the divided cell is selected from the group consisting of: platinum mesh, platinum sheet or graphite electrodes; the diaphragm of the divided cell is selected from: n-117 proton membrane or HF-101 strong acid type cation exchange membrane.
4. The process for preparing 1,2,3, 4-tetrahydro-1-naphthylamine compound according to claim 1, wherein the organic solvent in the catholyte is selected from: any one or more of acetonitrile, butyronitrile, methanol, ethanol, tetrahydrofuran or N, N dimethylformamide.
5. The method for preparing 1,2,3, 4-tetrahydro-1-naphthylamine compounds by electroreduction according to claim 1, wherein the concentration of the 3, 4-dihydronaphthalene-1 (2H) -ketoxime compounds in the catholyte is between 5.0g/L and 20.0 g/L.
6. The process for preparing 1,2,3, 4-tetrahydro-1-naphthylamine compound according to claim 1, wherein the concentration of alkali solution is selected from the group consisting of: 0.1mol/L, 0.2mol/L, 0.5mol/L, 1mol/L, 2mol/L, 3mol/L or 5 mol/L.
7. The process for preparing 1,2,3, 4-tetrahydro-1-naphthylamine compound according to claim 1, wherein the volume ratio of organic solvent to alkali solution in the catholyte is selected from: 1: 1 to 1: 10.
8. The process for the electroreductive preparation of 1,2,3, 4-tetrahydro-1-naphthylamine compounds according to claim 1, wherein the cathodic electrode of the divided cell is selected from the group consisting of: a zinc sheet electrode; the anode electrode of the divided cell is selected from: a platinum mesh electrode.
CN202210373506.1A 2022-04-11 2022-04-11 Dasotriprin electrochemical preparation method Pending CN114703492A (en)

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