CN115043757A - Method for continuously preparing benzamidine hydrochloride - Google Patents
Method for continuously preparing benzamidine hydrochloride Download PDFInfo
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- CN115043757A CN115043757A CN202210891543.1A CN202210891543A CN115043757A CN 115043757 A CN115043757 A CN 115043757A CN 202210891543 A CN202210891543 A CN 202210891543A CN 115043757 A CN115043757 A CN 115043757A
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- Prior art keywords
- catalyst
- benzamidine hydrochloride
- compound
- continuous process
- solution
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- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 23
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 229940125904 compound 1 Drugs 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- -1 methoxy, ethoxy Chemical group 0.000 claims abstract description 5
- 229940125782 compound 2 Drugs 0.000 claims abstract description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims abstract description 3
- 238000005086 pumping Methods 0.000 claims abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 239000003622 immobilized catalyst Substances 0.000 claims description 6
- XZHKVYYQQVEUBZ-UHFFFAOYSA-N [amino-(2-propoxyphenyl)methylidene]azanium;chloride Chemical compound Cl.CCCOC1=CC=CC=C1C(N)=N XZHKVYYQQVEUBZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000007664 blowing Methods 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 239000004005 microsphere Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000008367 deionised water Substances 0.000 claims description 3
- 229910021641 deionized water Inorganic materials 0.000 claims description 3
- 229910052697 platinum Inorganic materials 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 229910018072 Al 2 O 3 Inorganic materials 0.000 claims description 2
- 229910004298 SiO 2 Inorganic materials 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 230000014759 maintenance of location Effects 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000010924 continuous production Methods 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical group C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
- ZDXKXSZWRWSJQU-UHFFFAOYSA-N n'-hydroxy-2-propoxybenzenecarboximidamide Chemical compound CCCOC1=CC=CC=C1C(N)=NO ZDXKXSZWRWSJQU-UHFFFAOYSA-N 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical class CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- MXOQNVMDKHLYCZ-UHFFFAOYSA-N benzamidoxime Chemical compound ON=C(N)C1=CC=CC=C1 MXOQNVMDKHLYCZ-UHFFFAOYSA-N 0.000 description 1
- 239000010724 circulating oil Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
- B01J23/42—Platinum
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/40—Catalysts, in general, characterised by their form or physical properties characterised by dimensions, e.g. grain size
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/50—Catalysts, in general, characterised by their form or physical properties characterised by their shape or configuration
- B01J35/51—Spheres
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/60—Catalysts, in general, characterised by their form or physical properties characterised by their surface properties or porosity
- B01J35/61—Surface area
- B01J35/615—100-500 m2/g
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to the technical field of drug intermediate synthesis, in particular to a method for continuously preparing benzamidine hydrochloride; the method comprises the following steps:
Description
Technical Field
The invention relates to the technical field of synthesis of drug intermediates, in particular to a method for continuously preparing benzamidine hydrochloride.
Background
Benzamidine hydrochloride is a key intermediate of vardenafil analogues, N-hydroxy benzamidine is basically used for hydrogenation reduction in an autoclave in the prior art, the safety risk is high, and a catalyst is palladium carbon and is expensive.
Disclosure of Invention
The purpose of the invention is: overcomes the technical defects of high catalyst price and high reaction safety coefficient in the prior art, and provides a method for continuously preparing benzamidine hydrochloride.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a process for the continuous preparation of benzamidine hydrochloride, said intermediate being 2-ethoxy (or 2-propoxybenzamidine hydrochloride, comprising the steps of:
wherein: r is methoxy, ethoxy or propoxy;
firstly, pumping the solution of the compound 1 and hydrogen into a fixed bed reactor filled with a catalyst respectively, and then reacting at a certain temperature and a certain pressure to generate a compound 2.
Further, the reaction temperature of the compound 1 solution in the fixed bed is 50-150 ℃, and the retention time of the reaction liquid in the fixed bed is less than 15 min.
Further, the solvent used in the compound 1 solution is one or more of methanol, ethanol, isopropanol and acetic acid.
Further, the catalyst is a metal catalyst of immobilized platinum, and the carrier of the immobilized catalyst is SiO 2 、Al 2 O 3 Or one or more of activated carbon.
Further, the catalyst is microspheres with the diameter of 0.5-4 mm.
Further, the catalyst is microspheres with the diameter of 1-2 mm.
Further, the preparation method of the catalyst comprises the following steps:
s1 adding 15g chloroplatinic acid into 800g 5% NaOH aqueous solution and 50g spherical activated carbon (diameter 1-2mm), soaking for 3-4h, filtering, drying, and drying by air blast at 110 ℃ to constant weight;
s2, after drying by blowing, transferring the mixture to a tubular furnace, under the protection of nitrogen, heating the mixture for 1 hour to 350 ℃, then switching to hydrogen, reducing the mixture for 2 hours at the temperature of 350 ℃, and then switching to nitrogen to slowly cool the mixture to room temperature for later use;
s3 is soaked in 0.5 percent acetic acid aqueous solution for 24 hours, and then is filtered, washed twice by deionized water, and is dried by blowing at the temperature of 110 ℃ for 24 hours in 100 ℃ to obtain 45-50.00g of Pt/C immobilized catalyst (spherical with the diameter of 1-2 mm).
Further, the mass concentration of the compound 1 solution is 5-15%, the reaction temperature is 50-150 ℃, the reaction pressure is 0.5-30 Mpa, and the reaction residence time is less than 15 min.
Advantageous effects
The platinum catalyst (main producers: Shaanxi Rui Ke Li) available in the market at present has the defects of irregular active carbon as a carrier, uneven specific surface area, low mechanical strength, low activity and short service life, and improves the preparation process of the Pt carbon supported catalyst.
The method is a continuous, safe and reliable synthesis method, uses cheap catalyst, and is an effective method suitable for industrial production. The reaction solution does not need special treatment, and the purity of the product can reach more than 99 percent. Is an effective method with simple and safe operation, low cost and easy industrialized production.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions. If the temperature is not particularly emphasized, the reaction is usually carried out at room temperature, and the room temperature in the present invention is 10 to 30 ℃.
Example 1: preparation of the catalyst
(1)15g of chloroplatinic acid, 800g of 5 percent NaOH aqueous solution and 50g of spherical activated carbon (1-2mm) are added, soaked for 4 hours, filtered and dried, and blown and dried at the temperature of 100 ℃ and 110 ℃ to constant weight.
(3) After blast drying, transferring to a tubular furnace, heating to 350 ℃ for 1h under the protection of nitrogen, then switching to hydrogen, reducing at 350 ℃ for 2h, and then switching to nitrogen to slowly cool to room temperature for later use.
(4) Soaking the catalyst in 0.5% acetic acid water solution for 24h, filtering, washing with deionized water twice, and drying by blowing at the temperature of 110 ℃ for 24h to obtain 48.00g of Pt/C immobilized catalyst.
| Catalyst producer | Specific surface area (m2/g) | Mechanical Strength (N/grain) | Percent conversion in the reaction% | Life span |
| Xian Kaili | 100-200 | 20-30 | 90.0 | 6 days |
| Self-made | 280-360 | 50-80 | 97.5 | 10 days |
Example 2: intermittent mode
Adding 2-propoxy-N-hydroxybenzamidine (100.0g), acetic acid (500mL) and 10% palladium carbon (10g) into an autoclave, replacing 3 times with nitrogen and 3 times with hydrogen, heating to 60 ℃ for reaction for 4-8h, cooling to room temperature after the reaction is completed, filtering out the palladium carbon, adding concentrated hydrochloric acid (80g), concentrating, adding toluene (100mL), concentrating to dryness, adding 500mL methyl tert-butyl ether for crystallization, performing suction filtration and drying to obtain 104.5g of 2-propoxybenzamidine hydrochloride, LC-MS (M +1):179.20, wherein the HPLC purity is 99.2%, and the yield is as follows: 94.5 percent
Example 3: continuous mode
4.5g of self-made Pt/C immobilized catalyst is added into a European Shengshi full-automatic hydrogenation instrument (a packed column is 5.6mL), after nitrogen replacement, the hydrogen backpressure is switched to 2.5Mpa, hydrogen starts to be introduced, 35mL/min is carried out, a feeding pump is started at the temperature of 80 ℃, a raw material liquid containing (100g of 2-propoxy-N-hydroxybenzamidine, 500g of ethanol and 100g of acetic acid) is conveyed into a reactor, the flow is 0.35mL/min, sampling is carried out after the system is stable, and the reaction is qualified. Concentrated hydrochloric acid (80g) was added to the reaction mixture, concentrated to dryness, and 500mL of methyl t-butyl ether was added to the mixture to conduct crystallization, followed by suction filtration and drying to obtain 106.0g of 2-propoxybenzamidine hydrochloride, LC-MS (M +1):179.20,1HNMR (δ ppm, DMSO-d6, 400MHz)9.42(s, 2H),9.21(s, 2H),7.58 to 7.62(t, 1H, J ═ 4Hz),7.52 to 7.54(d,1H, J ═ 8Hz),7.22 to 7.24(d,1H, J ═ 8Hz),7.08 to 7.12(t, 1H, J ═ 4Hz),4.02 to 4.06(t,2H, J ═ 8Hz), 1.72 to 1.80(M, 2H),0.97 to 1.01(t,3H, J ═ 4Hz), HPLC 99.3%, purity: 95.9 percent.
Example 4: continuous mode
40.00g of self-made Pt/C supported catalyst is added into a 55mL filling column (with a jacket), the back pressure of nitrogen is 2.5Mpa, hydrogen is switched in, and hydrogen is introduced for replacement for 10min, and the flow rate is 250 mL/min.
Setting the temperature of jacket circulating oil at 80 ℃, starting a feeding pump after the temperature is constant, conveying a raw material liquid containing (500g of 2-propoxy-N-hydroxybenzamidine, 2500g of ethanol and 500g of acetic acid) into a reactor, wherein the flow rate is 3.5mL/min, sampling is started after the system is stable, and the reaction is qualified. Concentrated hydrochloric acid (400g) is added into the reaction solution, concentrated to dryness, 2.5L methyl tert-butyl ether is added into the reaction solution for crystallization, and 525.0g of 2-propoxybenzamidine hydrochloride is obtained after suction filtration and drying, the HPLC purity is 98.9 percent, and the yield is as follows: 94.9 percent.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the appended claims.
Claims (8)
1. A process for the continuous preparation of benzamidine hydrochloride, the intermediate being 2-ethoxy (or 2-propoxy benzamidine hydrochloride, characterized in that it comprises the steps of:
wherein: r is methoxy, ethoxy or propoxy;
firstly, pumping the solution of the compound 1 and hydrogen into a fixed bed reactor filled with a catalyst respectively, and then reacting at a certain temperature and a certain pressure to generate a compound 2.
2. The continuous process for preparing benzamidine hydrochloride according to claim 1, characterized in that: the reaction temperature of the compound 1 solution in the fixed bed is 50-150 ℃, and the residence time of the reaction liquid in the fixed bed is less than 15 min.
3. The continuous process for preparing benzamidine hydrochloride according to claim 1, characterized in that: the solvent used by the compound 1 solution is one or more of methanol, ethanol, isopropanol and acetic acid.
4. The continuous process for preparing benzamidine hydrochloride according to claim 1A method of salt, characterized by: the catalyst is a metal catalyst of immobilized platinum, and the carrier of the immobilized catalyst is SiO 2 、Al 2 O 3 Or one or more of activated carbon.
5. The continuous process for preparing benzamidine hydrochloride according to claim 1, characterized in that: the catalyst is a microsphere with the diameter of 0.5-4 mm.
6. The continuous process for preparing benzamidine hydrochloride according to claim 1, characterized in that: the catalyst is microspheres with the diameter of 1-2 mm.
7. The continuous process for the preparation of benzamidine hydrochloride according to any one of claims 4-6, characterized in that: the preparation method of the catalyst comprises the following steps:
s1 adding 15g chloroplatinic acid into 800g 5% NaOH aqueous solution and 50g spherical activated carbon (diameter 1-2mm), soaking for 3-4h, filtering, drying, and drying by air blast at 110 ℃ to constant weight;
s2, after drying by blowing, transferring the mixture to a tubular furnace, under the protection of nitrogen, heating the mixture for 1 hour to 350 ℃, then switching to hydrogen, reducing the mixture for 2 hours at the temperature of 350 ℃, and then switching to nitrogen to slowly cool the mixture to room temperature for later use;
s3 is soaked in 0.5 percent acetic acid aqueous solution for 24 hours, and then is filtered, washed twice by deionized water, and is dried by blowing at the temperature of 110 ℃ for 24 hours in 100 ℃ to obtain 45-50.00g of Pt/C immobilized catalyst (spherical with the diameter of 1-2 mm).
8. The continuous process for preparing benzamidine hydrochloride according to claim 1, characterized in that: the mass concentration of the compound 1 solution is 5-15%, the reaction temperature is 50-150 ℃, the reaction pressure is 0.5-30 Mpa, and the reaction retention time is less than 15 min.
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| CN202210891543.1A CN115043757B (en) | 2022-07-27 | 2022-07-27 | Method for continuously preparing benzamidine hydrochloride |
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| CN202210891543.1A CN115043757B (en) | 2022-07-27 | 2022-07-27 | Method for continuously preparing benzamidine hydrochloride |
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| CN1846852A (en) * | 2005-04-15 | 2006-10-18 | 北京有色金属研究总院 | Prepn process of carbon supported platinum catalyst |
| CN1830955A (en) * | 2005-11-07 | 2006-09-13 | 山东师范大学 | Method for synthesizing O-ethoxy phenyl formamidine acetate |
| CN101029023A (en) * | 2007-02-02 | 2007-09-05 | 广东东阳光药业有限公司 | Production of picolyl ether and its salt |
| CN101502797A (en) * | 2008-12-30 | 2009-08-12 | 西安凯立化工有限公司 | Platinum-based selective hydrogenation catalyst as well as preparation method and use thereof |
| CN103349983A (en) * | 2013-07-27 | 2013-10-16 | 西安凯立化工有限公司 | Catalyst for preparing halogenated aniline through catalytic hydrogenation of halogenated nitrobenzene and application thereof |
| CN104549235A (en) * | 2014-12-19 | 2015-04-29 | 上海交通大学 | Preparation method of carbon supported nano platinum catalyst |
| CN106252677A (en) * | 2016-08-03 | 2016-12-21 | 陕西瑞科新材料股份有限公司 | A kind of preparation method of charcoal platinum catalyst |
| CN106565539A (en) * | 2016-11-05 | 2017-04-19 | 王密治 | Method for synthesizing benzamidine derivative |
| CN110878032A (en) * | 2019-10-31 | 2020-03-13 | 苏州诚和医药化学有限公司 | Synthesis method of N-benzylacetamidine hydrochloride |
| CN112934218A (en) * | 2019-12-10 | 2021-06-11 | 中国科学院大连化学物理研究所 | Platinum-carbon catalyst, preparation and application thereof |
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