CN103113305B - Synthetic method for bendazol and salt thereof - Google Patents
Synthetic method for bendazol and salt thereof Download PDFInfo
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- CN103113305B CN103113305B CN201310046699.0A CN201310046699A CN103113305B CN 103113305 B CN103113305 B CN 103113305B CN 201310046699 A CN201310046699 A CN 201310046699A CN 103113305 B CN103113305 B CN 103113305B
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- YTLQFZVCLXFFRK-UHFFFAOYSA-N bendazol Chemical compound N=1C2=CC=CC=C2NC=1CC1=CC=CC=C1 YTLQFZVCLXFFRK-UHFFFAOYSA-N 0.000 title claims abstract description 63
- 229950000900 bendazol Drugs 0.000 title claims abstract description 57
- 238000010189 synthetic method Methods 0.000 title claims abstract description 21
- 150000003839 salts Chemical class 0.000 title abstract description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- CJTQARUHALKPGG-UHFFFAOYSA-N 2-benzyl-1h-benzimidazole;hydron;chloride Chemical compound Cl.N=1C2=CC=CC=C2NC=1CC1=CC=CC=C1 CJTQARUHALKPGG-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000003756 stirring Methods 0.000 claims abstract description 16
- 239000000463 material Substances 0.000 claims abstract description 12
- 238000001816 cooling Methods 0.000 claims abstract description 7
- 238000010792 warming Methods 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 13
- 239000000155 melt Substances 0.000 claims description 7
- 238000009413 insulation Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 abstract description 11
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 6
- 239000002904 solvent Substances 0.000 abstract description 6
- 238000010438 heat treatment Methods 0.000 abstract description 5
- 239000003960 organic solvent Substances 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 3
- 238000001914 filtration Methods 0.000 abstract description 3
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 abstract 2
- 229960003424 phenylacetic acid Drugs 0.000 abstract 1
- 239000003279 phenylacetic acid Substances 0.000 abstract 1
- 239000000376 reactant Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 32
- 239000003513 alkali Substances 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000013558 reference substance Substances 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical group C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 208000004929 Facial Paralysis Diseases 0.000 description 1
- 206010070538 Gestational hypertension Diseases 0.000 description 1
- 201000005624 HELLP Syndrome Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 208000005347 Pregnancy-Induced Hypertension Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RIIWUGSYXOBDMC-UHFFFAOYSA-N benzene-1,2-diamine;hydron;dichloride Chemical compound Cl.Cl.NC1=CC=CC=C1N RIIWUGSYXOBDMC-UHFFFAOYSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 208000036335 preeclampsia/eclampsia 1 Diseases 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a synthetic method for bendazol and salt thereof; the synthetic method comprises the following steps of: using o-phenylenediamine and phenylacetic acid as raw material, without adding any catalyst and solvent, only under the protection of nitrogen, carrying out gradient heating and cooling reaction under the condition of a certain temperature, specifically, heating to 80-100 DEG C first, after the material are all melted, stirring, heating to 140-160 DEG C, holding for 1-4 hours, and then heating to 180-200 DEG C and holding for 1-4 hours, then cooling to 80-100 DEG C, adding hot water into reactant, wherein the temperature of the hot water is 80-95 DEG C, stirring uniformly after the hot water is added, cooling, filtering, so as to obtain bendazol; salifying bendazol with diluted hydrochloric acid, so as to obtain bendazol hydrochloride. In the method, organic solvent and catalyst are not used, the three wastes are almost avoided, and the yield reaches higher than 90%, and thus the synthetic method is green and environment-friendly and is suitable for industrial mass production.
Description
Technical field
The invention belongs to pharmaceutical synthesis field, be specifically related to the synthetic method of a kind of dibazol and salt thereof.
Background technology
Dibazol, chemistry is by name: Bendazol, English name: 2-(Phenylmethyl)-1H-benzimidazole, molecular formula: C
14h
12n
2, molecular weight: 208.25, structural formula is as shown in the formula shown in I:
formula I.
The salt that dibazol is conventional is generally dibazol hydrochloride, molecular formula: C
14h
13clN
2, molecular weight: 244.72, structural formula is as shown in the formula shown in II:
formula II.
Dibazol has vasodilator, reduces blood pressure and removes smooth muscle spasm and excited spinal cord effect, for hypertension, stenocardia, pregnancy induced hypertension syndrome, cramps of gastrointestinal tract, poliomyelitis sequela and periphery peripheral facial paralysis etc.
At present, synthesis document about dibazol is more, document Helvetica Chimica Acta-Vol.(94 (2011), 1860 ~ 1874) synthetic method of dibazol is reported, namely with O-Phenylene Diamine and toluylic acid for raw material, under boric acid catalysis, be at high temperature obtained by reacting dibazol, the shortcoming of the method is, needs to use acid as catalyzer.
Chinese patent ZL200910143972.5 discloses a kind of preparation method of dibazol hydrochloride, comprises the following steps: O-Phenylene Diamine and toluylic acid are dissolved in alcoholic solvent, add dewatering agent, is warming up to 100 ~ 130 DEG C and reacts at this temperature; Reaction solution is cooled to room temperature, suction filtration, filtrate decompression recycling design is to dry; Be dissolved in water, adjust pH, add activated carbon decolorizing filtration, filtrate crystallisation by cooling is dry obtains dibazol hydrochloride; Wherein, described dewatering agent is dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylamino-propyl) carbon imide hydrochloride, N, N-carbonyl dimidazoles, n-propyl phosphoric anhydride.The method, using alcoholic solvent as the catalysts and solvents of condensation reaction, adopts cheap dewatering agent, avoids the highly corrosive using strong acid as catalyzer, and greatly reduces the temperature of reaction, improve speed of reaction, Reaction time shorten; And reaction solvent can recycled, has saved production cost.But the method still needs to use a large amount of organic solvents and organic dewatering agent, is unfavorable for environment protection.
Chinese patent ZL201010242848.7 discloses a kind of preparation method of dibazol, the steps include: A, be that 1: 1.05-1.2 reacting by heating prepares o-phenylendiamine dihydrochloride in molar ratio by O-Phenylene Diamine and feeding intake of concentrated hydrochloric acid, temperature controls at 70-80 DEG C, and the reaction times is at 30-45min; B, by the dibazol hydrochloride in step A and C
6h
5cH
2-R by ingredient proportion be in molar ratio 1: 1.06-1.2 160-200 DEG C reaction condensation reaction, the reaction times: 1-1.5 hour; Obtained dibazol.The method method is simple, easy to operate, low raw-material cost, and yield is high, also pollution-free to environment, is very suitable for suitability for industrialized production, and the yield producing dibazol can up to 96.2%.But the method first generates dibazol hydrochloride due to needs, still need the concentrated hydrochloric acid using severe corrosive, strong to the corrodibility of equipment.
Summary of the invention
The object of this invention is to provide a kind of dibazol of environmental protection and the synthetic method of salt thereof, the method does not use organic solvent and catalyzer, does not almost have the three wastes, and yield is high, is very applicable to industrialized production.
The present invention with O-Phenylene Diamine and toluylic acid for raw material; do not add any catalyzer and solvent; under nitrogen protection; react under certain temperature condition, after reaction terminates, be down to certain temperature; hot water is added in reaction solution; cold filtration, obtains dibazol alkali (i.e. dibazol), becomes salt refining namely to obtain dibazol dibazol alkali in water with hydrochloric acid.Synthetic route of the present invention as shown in Figure 1.
The synthetic method of dibazol provided by the invention and salt thereof is specific as follows:
A synthetic method for dibazol, comprises the steps:
O-Phenylene Diamine and toluylic acid are joined in reaction vessel with the proportioning of mol ratio 1:1 ~ 1.5; first with nitrogen replacement to anaerobic; continue inflated with nitrogen protection again; first be warming up to 80 DEG C ~ 100 DEG C; after material all melts; stir, be warming up to 140 DEG C ~ 160 DEG C insulations 1 ~ 4 hour, and then be warming up to 180 DEG C ~ 200 DEG C insulations 1 ~ 4 hour; be cooled to 80 DEG C ~ 100 DEG C afterwards; in reaction solution, add hot water, hot water temperature is 80 DEG C ~ 95 DEG C, after adding; stir; cooling, filters, obtains dibazol.
Angularly consider from raising reaction yield, preferably, the mol ratio of O-Phenylene Diamine, toluylic acid is 1:1.1 ~ 1.2.After inflated with nitrogen protection, be preferably first warming up to 90 DEG C ~ 95 DEG C, after material all melts; stir, be warming up to 145 DEG C ~ 150 DEG C insulations 2 ~ 3 hours, and then be warming up to 185 DEG C ~ 190 DEG C insulations 2 ~ 3 hours; be cooled to 90 DEG C ~ 95 DEG C afterwards; in reaction solution, add hot water, hot water temperature is 85 DEG C ~ 90 DEG C, after adding; stir; cooling, filters, obtains dibazol.
Described with nitrogen replacement to anaerobic, preferably use nitrogen replacement 3 times, substantially can reach required effect.
A synthetic method for dibazol salt, comprises the steps:
Be added in by dibazol in water, be warming up to 65 DEG C ~ 80 DEG C, drip the dilute hydrochloric acid of massfraction 10% ~ 20%, adjust ph is 3 ~ 4.5, decrease temperature crystalline, filters, dry dibazol hydrochloride.
In the synthetic method of dibazol salt, angularly consider from raising reaction yield, preferably, be warming up to 70 DEG C ~ 75 DEG C, drip the dilute hydrochloric acid of massfraction 15% ~ 18%; Preferred adjust ph is 3.5 ~ 4.0.The dibazol that described dibazol can adopt existing commercially available dibazol also can adopt synthetic method of the present invention to synthesize, preferably adopts the dibazol of synthetic method of the present invention synthesis, is more conducive to protection of the environment.
The inventive method has following beneficial effect:
The synthetic method of dibazol of the present invention with O-Phenylene Diamine and toluylic acid for raw material; do not add any catalyzer and solvent; just under nitrogen protection; temperature-gradient method, hypothermic response is carried out under certain temperature condition; obtain dibazol; yield more than 90%, under optimum condition, yield can reach more than 95%, has good industrial applications prospect.The method does not use organic solvent and catalyzer, does not almost have the three wastes, and yield is high, is a kind of environmental protection and is suitable for the synthetic method of industrialized production.
The synthetic method of dibazol salt of the present invention with dibazol and dilute hydrochloric acid for raw material, almost there is no the three wastes, and yield is high, is a kind of environmental protection and is suitable for the synthetic method of industrialized production.
Accompanying drawing explanation
Fig. 1 is synthetic route chart of the present invention.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail.
Embodiment 1
50g (0.4624mol) O-Phenylene Diamine is added in reaction flask; 72.4g(0.5318mol) toluylic acid; first use nitrogen replacement 3 times, then continue inflated with nitrogen protection, be warming up to 90 DEG C; after material all melts; open stirring, be warming up to 145 DEG C, be incubated 2 hours; be warming up to 185 DEG C again; be incubated 2 hours, be cooled to 90 DEG C subsequently, add 800ml85 DEG C of hot water; after stirring; be cooled to 60 DEG C, filter, obtain dibazol alkali wet product; obtain dry product 91.5g after drying, molar yield is that 95%(is in O-Phenylene Diamine).
This dry product product is through contrasting with dibazol reference substance, and HPLC goes out peak position, and mass spectrum is all consistent, shows that this product is dibazol alkali.
HPLC condition is:
Instrument: high performance liquid chromatograph; UV-detector;
Chromatographic column: C18;
Moving phase: acetonitrile: water=80:20, volume ratio;
Flow velocity: 1.0mL/min;
Column temperature: room temperature;
Sample size: 20 μ l;
Determined wavelength: 250nm;
LC-MS:m/e209.1 (M
++ 1) show that the molecular weight of this material is 208.25, consistent with the molecular weight of dibazol alkali.
Embodiment 2
Dibazol alkali 91.5g prepared by embodiment 1 is added in reaction flask, add 300ml water, be warming up to 70 DEG C, dripping massfraction is the dilute hydrochloric acid of 15%, and adjust pH is 3.5, after mixing up, be cooled to 0 DEG C, filter, dry, obtain product dibazol hydrochloride 96.8g, molar yield 85.55%(is in O-Phenylene Diamine).
This product is through contrasting with dibazol hydrochloride reference substance, and infared spectrum and nuclear magnetic spectrum are all consistent, show that this product is dibazol hydrochloride.
IR(KBr):1536,1401,1456,1426。
1H-NMR(300MHz，(D
6)DMSO):4.17(s,2H)；7.05-7.17(m,2H)；7.19-7.35(m,5H)；7.37-7.58(m,2H)；12.26(br.s,1H)。
Embodiment 3
50g (0.4624mol) O-Phenylene Diamine is added in reaction flask; 75.5g(0.5545mol) toluylic acid; first use nitrogen replacement 3 times, then continue inflated with nitrogen protection, be warming up to 95 DEG C; after material all melts; open stirring, be warming up to 150 DEG C, be incubated 3 hours; be warming up to 190 DEG C again; be incubated 3 hours, be cooled to 95 DEG C subsequently, add 800ml90 DEG C of hot water; after stirring; be cooled to 60 DEG C, filter, obtain dibazol alkali wet product; obtain dry product 92g after drying, molar yield is that 95.5%(is in O-Phenylene Diamine).
This dry product product is through contrasting with dibazol reference substance, and HPLC goes out peak position, and mass spectrum is all consistent, shows that this product is dibazol alkali.
HPLC condition is with embodiment 1.
LC-MS:m/e209.1 (M
++ 1) show that the molecular weight of this material is 208.25, consistent with the molecular weight of dibazol alkali.
Embodiment 4
Dibazol alkali 92g prepared by embodiment 3 is added in reaction flask, add 300ml water, be warming up to 75 DEG C, dripping massfraction is the dilute hydrochloric acid of 18%, and adjust pH is 4.0, after mixing up, be cooled to 5 DEG C, filter, dry, obtain product dibazol hydrochloride 97g, molar yield 85.7%(is in O-Phenylene Diamine).
This product is through contrasting with dibazol hydrochloride reference substance, and infared spectrum and nuclear magnetic spectrum are all consistent, show that this product is dibazol hydrochloride.
IR(KBr):1536,1401,1456,1426。
1H-NMR(300MHz，(D
6)DMSO):4.17(s,2H)；7.05-7.17(m,2H)；7.19-7.35(m,5H)；7.37-7.58(m,2H)；12.26(br.s,1H)。
Embodiment 5
50g (0.4624mol) O-Phenylene Diamine is added in reaction flask; 62.95g(0.4624mol) toluylic acid; first use nitrogen replacement 3 times, then continue inflated with nitrogen protection, be warming up to 80 DEG C; after material all melts; open stirring, be warming up to 140 DEG C, be incubated 1 hour; be warming up to 180 DEG C again; be incubated 1 hour, be cooled to 80 DEG C subsequently, add 800ml80 DEG C of hot water; after stirring; be cooled to 55 DEG C, filter, obtain dibazol alkali wet product; obtain dry product 90.1g after drying, molar yield is that 93.6%(is in O-Phenylene Diamine).
This dry product product is through contrasting with dibazol reference substance, and HPLC goes out peak position, and mass spectrum is all consistent, shows that this product is dibazol alkali.
HPLC condition is with embodiment 1.
LC-MS:m/e209.1 (M
++ 1) show that the molecular weight of this material is 208.25, consistent with the molecular weight of dibazol alkali.
Embodiment 6
Dibazol alkali 90.1g prepared by embodiment 5 is added in reaction flask, add 300ml water, be warming up to 65 DEG C, dripping massfraction is the dilute hydrochloric acid of 10%, and adjust pH is 3.0, after mixing up, be cooled to 0 DEG C, filter, dry, obtain product dibazol hydrochloride 94.5g, molar yield 83.2%(is in O-Phenylene Diamine).
This product is through contrasting with dibazol hydrochloride reference substance, and infared spectrum and nuclear magnetic spectrum are all consistent, show that this product is dibazol hydrochloride.
IR(KBr):1536,1401,1456,1426。
1H-NMR(300MHz，(D
6)DMSO):4.17(s,2H)；7.05-7.17(m,2H)；7.19-7.35(m,5H)；7.37-7.58(m,2H)；12.26(br.s,1H)。
Embodiment 7
50g (0.4624mol) O-Phenylene Diamine is added in reaction flask; 62.95g(0.6936mol) toluylic acid; first use nitrogen replacement 3 times, then continue inflated with nitrogen protection, be warming up to 100 DEG C; after material all melts; open stirring, be warming up to 160 DEG C, be incubated 4 hours; be warming up to 200 DEG C again; be incubated 4 hours, be cooled to 100 DEG C subsequently, add 800ml95 DEG C of hot water; after stirring; be cooled to 50 DEG C, filter, obtain dibazol alkali wet product; obtain dry product 89.8g after drying, molar yield is that 93.3%(is in O-Phenylene Diamine).
This dry product product is through contrasting with dibazol reference substance, and HPLC goes out peak position, and mass spectrum is all consistent, shows that this product is dibazol alkali.
HPLC condition is with embodiment 1.
LC-MS:m/e209.1 (M
++ 1) show that the molecular weight of this material is 208.25, consistent with the molecular weight of dibazol alkali.
Embodiment 8
Dibazol alkali 89.8g prepared by embodiment 7 is added in reaction flask, add 300ml water, be warming up to 80 DEG C, dripping massfraction is the dilute hydrochloric acid of 20%, and adjust pH is 4.5, after mixing up, be cooled to 0 DEG C, filter, dry, obtain product dibazol hydrochloride 94g, molar yield 82.8%(is in O-Phenylene Diamine).
This product is through contrasting with dibazol hydrochloride reference substance, and infared spectrum and nuclear magnetic spectrum are all consistent, show that this product is dibazol hydrochloride.
IR(KBr):1536,1401,1456,1426。
1H-NMR(300MHz，(D
6)DMSO):4.17(s,2H)；7.05-7.17(m,2H)；7.19-7.35(m,5H)；7.37-7.58(m,2H)；12.26(br.s,1H)。
In synthetic method of the present invention, the change of parameter does not affect the synthesis of dibazol and dibazol hydrochloride, and therefore in synthetic method of the present invention, the combination of arbitrary parameter all can realize the preparation of dibazol and dibazol hydrochloride.Do not repeat them here.
Claims (1)
1. a synthetic method for dibazol salt, is characterized in that, comprises step:
(1) O-Phenylene Diamine and toluylic acid are joined in reaction vessel with the proportioning of mol ratio 1:1.1 ~ 1.2, first with nitrogen replacement to anaerobic, continue inflated with nitrogen protection again, first be warming up to 90 DEG C ~ 95 DEG C, after material all melts, stir, be warming up to 145 DEG C ~ 150 DEG C insulations 2 ~ 3 hours, and then be warming up to 185 DEG C ~ 190 DEG C insulations 2 ~ 3 hours, be cooled to 90 DEG C ~ 95 DEG C afterwards, in reaction solution, add hot water, hot water temperature is 85 DEG C ~ 90 DEG C, after adding, stir, cooling, filters, obtains dibazol;
(2) be added in water by dibazol, be warming up to 70 DEG C ~ 75 DEG C, drip the dilute hydrochloric acid of massfraction 15% ~ 18%, adjust ph is 3.5 ~ 4.0, decrease temperature crystalline, filters, dry dibazol hydrochloride.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101891688A (en) * | 2010-07-30 | 2010-11-24 | 孝感市诚嘉药物研究所 | Preparation method for bendazol in industrialized production |
| CN101906074A (en) * | 2009-06-04 | 2010-12-08 | 浙江医药股份有限公司新昌制药厂 | Preparation method of dibazol hydrochloride |
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2013
- 2013-02-06 CN CN201310046699.0A patent/CN103113305B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101906074A (en) * | 2009-06-04 | 2010-12-08 | 浙江医药股份有限公司新昌制药厂 | Preparation method of dibazol hydrochloride |
| CN101891688A (en) * | 2010-07-30 | 2010-11-24 | 孝感市诚嘉药物研究所 | Preparation method for bendazol in industrialized production |
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