CN101863840B - Preparation method of 5-amino-6-methyl benzimidazolone - Google Patents
Preparation method of 5-amino-6-methyl benzimidazolone Download PDFInfo
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- CN101863840B CN101863840B CN2010102020482A CN201010202048A CN101863840B CN 101863840 B CN101863840 B CN 101863840B CN 2010102020482 A CN2010102020482 A CN 2010102020482A CN 201010202048 A CN201010202048 A CN 201010202048A CN 101863840 B CN101863840 B CN 101863840B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- ZCXIPVIGYBHUTQ-UHFFFAOYSA-N 5-amino-6-methyl-1,3-dihydrobenzimidazol-2-one Chemical compound C1=C(N)C(C)=CC2=C1NC(=O)N2 ZCXIPVIGYBHUTQ-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000006722 reduction reaction Methods 0.000 claims abstract description 23
- IOQXONVXJBPYAB-UHFFFAOYSA-N 5-methyl-6-nitrobenzimidazol-2-one Chemical compound C1=C([N+]([O-])=O)C(C)=CC2=NC(=O)N=C21 IOQXONVXJBPYAB-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 15
- CTCHXZUMFHNSHM-UHFFFAOYSA-N 5-methyl-1,3-dihydrobenzimidazol-2-one Chemical compound CC1=CC=C2NC(=O)NC2=C1 CTCHXZUMFHNSHM-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims abstract description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000004202 carbamide Substances 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 5
- 238000009833 condensation Methods 0.000 claims abstract description 5
- 230000005494 condensation Effects 0.000 claims abstract description 5
- 238000006396 nitration reaction Methods 0.000 claims abstract description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910017604 nitric acid Inorganic materials 0.000 claims abstract description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 15
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 claims description 10
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 7
- 229910052759 nickel Inorganic materials 0.000 claims description 4
- MEVPRMYSNBGYJU-UHFFFAOYSA-N 5-amino-6-methylbenzimidazol-2-one Chemical class C1=C(N)C(C)=CC2=NC(=O)N=C21 MEVPRMYSNBGYJU-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 11
- DGRGLKZMKWPMOH-UHFFFAOYSA-N 4-methylbenzene-1,2-diamine Chemical compound CC1=CC=C(N)C(N)=C1 DGRGLKZMKWPMOH-UHFFFAOYSA-N 0.000 abstract description 4
- 239000012847 fine chemical Substances 0.000 abstract description 3
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 238000011946 reduction process Methods 0.000 abstract 3
- 238000005984 hydrogenation reaction Methods 0.000 abstract 2
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 abstract 1
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 abstract 1
- 239000000843 powder Substances 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 30
- 239000000047 product Substances 0.000 description 26
- 238000009413 insulation Methods 0.000 description 24
- 238000010438 heat treatment Methods 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 238000010992 reflux Methods 0.000 description 15
- 238000013019 agitation Methods 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 238000004062 sedimentation Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000002826 coolant Substances 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 241001411320 Eriogonum inflatum Species 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000010009 beating Methods 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000001546 nitrifying effect Effects 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
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- 239000013078 crystal Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
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- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a preparation method of 5-amino-6-methyl benzimidazolone, belonging to the technical field of a compound preparation method, in particular to a preparation method of fine chemical intermediate. The preparation method is characterized by sequentially comprising the following steps of: carrying out condensation on 3, 4-diaminotoluene and urea, and preparing 5-methyl benzimidazolone; carrying out nitration reaction on the 5-methyl benzimidazolone under the condition of dilute nitric acid, and preparing 5-nitro-6-methyl benzimidazolone; and finally, carrying out reduction reaction on the 5-nitro-6-methyl benzimidazolone, and preparing the target compound of 5-amino-6-methyl benzimidazolone. In the reduction process of ferrous powder of the reduction reaction of the preparation method, alcohol-water system is taken as a solvent, and the system has low toxicity. In the process of hydrogenation reduction process, DMF-water system is taken as a solvent, and the solvent can be easily recovered, so that the cost is saved. In the process of hydrogenation reduction process, Nguyen Ni or Pd carbon is taken as a catalyst, so that the catalysis effect is good, the cost is low, and the synthetic route has simple technique.
Description
Technical field
The invention belongs to the compounds process for production thereof technical field, be specifically related to a kind of preparation method of fine-chemical intermediate.
Background technology
5-amino-6-methyl benzimidazolone is a kind of of great value fine-chemical intermediate, and it not only is applied to the synthetic of multiple pigment dyestuff, also is applied to dyestuff, medicine and other fields simultaneously.Entered since the later stage eighties, the gram Lay benefactor department of many beautiful years companies of Canada, Germany, many companies such as Qi Bajiaji company of Switzerland the Application Areas of this product has all been done go deep into, extensive studies, also obtain simultaneously very big progress, obtained the very good deep processed product of a lot of application performances.But up to the present, the report document of the synthetic aspect of 5-amino-6-methyl benzimidazolone seldom, we only find the report of the synthetic document of three pieces of relevant 5-amino-6 methyl benzimidazolones in the retrieval that comprises pertinent literatures such as CA and Beil..In the middle of these three pieces of documents, Russia's document is published in 1958 28 phases of Zhurnal obshchen kuim ü, the synthetic method of this article introduction is, with 5-nitro-6-methyl benzimidazolone is starting raw material, under the concentrated hydrochloric acid condition, carry out reduction reaction with tin, this technology does not finally obtain purified target product, but the hydrochloride of target product, yield is 71.3%.Second piece of article is U.S. Pat 6,087,480.1998 year (identical with world patent WO 99/36402.1999), this patent adopt 5-nitro-6-methyl benzimidazolone to make starting raw material equally, take the method for shortening to reduce and obtain target product, yield is 93%.But this patent is not reported the quality situation of products therefrom, and the used catalyzer of this technology hydrogenating reduction is homemade, clear and definite elaboration is not done in the manufacturing of catalyzer in the patent.The 3rd piece of document, be that Australian Cortical Pty Ltd. is in Chinese patents, patent publication No. is CN1675185, and this patent adopts cyclization, nitrated, three step of reduction unit operation routes to realize the synthetic of target product, on the data of its report, cyclization yield 56%, what reduction reaction adopted is palladium carbon shortening, and this technology has obtained qualified target product, does not report reductive yield situation, from the cyclization yield, raw materials cost is than higher.
Summary of the invention
The technical problem that the present invention solves is: the preparation method of 5-amino-6-methyl benzimidazolone is provided, yield is improved.
The present invention will solve the technical scheme that its technical problem adopts: the preparation method of a kind of 5-amino-6-methyl benzimidazolone is provided, it is characterized in that in turn including the following steps:
(1) with 3, the 4-diaminotoluene carries out condensation with urea, preparation 5-methyl benzimidazolone;
(2) with the 5-methyl benzimidazolone, under rare nitric acid condition, carry out nitration reaction, make 5-nitro-6-methyl benzimidazolone;
(3) 5-nitro-6-methyl benzimidazolone passes through reduction reaction again, makes target compound 5-amino-6-methyl benzimidazolone
The present invention is an orthodichlorobenzene at the used solvent of step (1) condensation.The used temperature of step (1) is 130-185 ℃.The nitration reaction temperature that step (2) is adopted is 2530 ℃.The reduction mode that step (3) is adopted is iron powder reducing or hydrogenating reduction.The solvent that the iron powder reducing process is adopted is an ethanol-water system, and the solvent that hydrogenating reduction adopts is the DMF-aqueous systems.The solvent strength that reduction reaction adopted is: ethanol quality percentage composition is 80-90% in the ethanol-water system, and the DMF weight content is 70-90% in the DMF-aqueous systems.The catalyzer that hydrogenating reduction adopted is Ruan Shi nickel or palladium carbon, and suitable catalyst levels is to be not less than 3% of 5-nitro-6-methyl benzimidazolone weight.
The beneficial effect that the present invention had is:
1. the 5-amino-6-methyl benzimidazolone by the present invention preparation, cyclization yield 98.5%, nitrated yield 98.3%, iron powder reducing yield 89.2%, hydrogenating reduction yield 91.8%.
2. the solvent that the iron powder reducing process is adopted in the reduction reaction is an ethanol-water system, this system low toxicity.The solvent that hydrogenating reduction adopts is the DMF-aqueous systems, and this solvent easily reclaims, and saves cost.The catalyzer that hydrogenating reduction adopted is Ruan Shi nickel or palladium carbon, and excellent catalytic effect is with low cost.
3. provide that a kind of technology is simple, the synthetic route of low production cost.
Embodiment
Below provide specific embodiment, the invention will be further described.
Embodiment one:
One stirring is installed, reflux exchanger, thermometer, in the 2000ml four-hole bottle of heating electric mantle, add the 1400g orthodichlorobenzene, start stirring then, under agitation condition to wherein adding 244g (2.0mol) 3,4-diaminotoluene and 123g (2.05mol) urea finishes, and opens the heating jacket heating system, with system temperature in 1.0 hours, slowly be warmed up to 143 ℃, and between 143-147 ℃ insulation reaction 5.5 hours, after insulation finishes, remove electric mantle, stir nature cooling down, after temperature is lower than 100 ℃, system temperature is continued to be reduced in 30 ℃ with water-bath, filter, washing is dried under infrared lamp then, gets 5-methyl benzimidazolone 293.6g, purity 99.3%, yield 98.5%.
Four-hole bottle with the 1000ml cleaning, install stirring, thermometer, feed hopper, water bath with thermostatic control, then to the nitric acid that wherein adds 814g 30% (3.876mol), start stirring, under agitation condition, system temperature is dropped to 25 ℃ with water-bath, in 2.0h, add 103.6g (0.70mol) 5-methyl benzimidazolone to system equably then, whole reinforced process is obviously with exothermic phenomenon, need to change often water coolant in the water-bath, to guarantee that whole reinforced process temperature maintains 25-30 ℃, finish the temperature range when keeping reinforced, continue insulation reaction 6.0h, after insulation finishes, filter with a B, the mother liquor recovery set is used, filter cake washes to washings with suitable quantity of water and is neutral, after draining filter cake is taken out, under infrared lamp, dry, get 5-nitro-6-methyl benzimidazolone 133.6g, purity 99.4%, yield 98.3%.
The 500ml four-hole bottle is installed stirring, condenser, thermometer, the heating electric mantle, then to wherein adding 250g 85% ethanol-water solution, start stirring, under agitation condition sequentially to wherein adding 16.8g (0.3mol) iron powder, 5.0g concentration is 36% hydrochloric acid, finish, build bottle stopper, open the reflux exchanger water coolant, open heating system, under agitation condition, system temperature is heated to and boils, keep being incubated under the boiling condition activation 30 minutes, then in 4.0 hours, evenly add 15g (0.078mol) 5-nitro-6-methyl benzimidazolone to system, fed in raw material once in per during this time 5 minutes, temperature maintains reflux state all the time, finish, reflux conditions continues insulation reaction 4.0h down, and insulation is finished, with yellow soda ash with the reaction solution PH=6.5-7.0 that neutralizes, continue to stir 10 minutes, stop then stirring, insulation sedimentation 20 minutes, filter with a B that is preheating near 100 ℃, iron mud is 85% alcohol reflux making beating 30 minutes with 200ml concentration, stops to stir insulation sedimentation 20 minutes then, filter, merge mother liquor and washing lotion, natural non-shock chilling is after cooling to room temperature, filter, products obtained therefrom is 50 ℃ of oven dry under infrared lamp, get the 11.4g product, purity 99.1%, outward appearance is the white plates crystallization, and yield is 89.2%.
Embodiment two:
One stirring is installed, reflux exchanger, thermometer, in the 2000ml four-hole bottle of heating electric mantle, add the 1400g orthodichlorobenzene, start stirring then, under agitation condition to wherein adding 244g (2.0mol) 3,4-diaminotoluene and 123g (2.05mol) urea finishes, and opens the heating jacket heating system, with system temperature in 1.0 hours, slowly be warmed up to 182 ℃, and between 182-185 ℃ insulation reaction 5.5 hours, after insulation finishes, remove electric mantle, stir nature cooling down, after temperature is lower than 100 ℃, system temperature is continued to be reduced in 30 ℃ with water-bath, filter, washing is dried under infrared lamp then, gets 5-methyl benzimidazolone 287.9g, purity 98.5%, yield 95.8%.
With above-mentioned products obtained therefrom by the nitrifying process among the embodiment one react 5-nitro-6-methyl benzimidazolone 133.8g, purity 99.2%, yield 98.2%.
The 500ml four-hole bottle is installed stirring, condenser, thermometer, the heating electric mantle, then to wherein adding 250g 80% ethanol-water solution, start stirring, under agitation condition sequentially to wherein adding 16.8g (0.3mol) iron powder, 5.0g concentration is 36% hydrochloric acid, finish, build bottle stopper, open the reflux exchanger water coolant, open heating system, under agitation condition, system temperature is heated to and boils, keep being incubated under the boiling condition activation 30 minutes, then in 4.0 hours, evenly add 15g (0.078mol) 5-nitro-6-methyl benzimidazolone to system, fed in raw material once in per during this time 5 minutes, temperature maintains reflux state all the time, finish, reflux conditions continues insulation reaction 4.0h down, and insulation is finished, with yellow soda ash with the reaction solution PH=6.5-7.0 that neutralizes, continue to stir 10 minutes, stop then stirring, insulation sedimentation 20 minutes, filter with a B that is preheating near 100 ℃, iron mud is 80% alcohol reflux making beating 30 minutes with 200ml concentration, stops to stir insulation sedimentation 20 minutes then, filter, merge mother liquor and washing lotion, natural non-shock chilling is after cooling to room temperature, filter, products obtained therefrom is 50 ℃ of oven dry under infrared lamp, get the 10.8g product, purity 99.3%, outward appearance is the white plates crystallization, and yield is 84.7%.
Embodiment three:
One stirring is installed, reflux exchanger, thermometer, in the 2000ml four-hole bottle of heating electric mantle, add the 1400g orthodichlorobenzene, start stirring then, under agitation condition to wherein adding 244g (2.0mol) 3,4-diaminotoluene and 123g (2.05mol) urea finishes, and opens the heating jacket heating system, with system temperature in 1.0 hours, slowly be warmed up to 131 ℃, and between 130-134 ℃ insulation reaction 7.5 hours, after insulation finishes, remove electric mantle, stir nature cooling down, after temperature is lower than 100 ℃, system temperature is continued to be reduced in 30 ℃ with water-bath, filter, washing is dried under infrared lamp then, gets 5-methyl benzimidazolone 273.4g, purity 98.3%, yield 90.8%.
With above-mentioned products obtained therefrom by the nitrifying process among the embodiment one react 5-nitro-6-methyl benzimidazolone 133.1g, purity 99.3%, yield 97.8%.
The 500ml four-hole bottle is installed stirring, condenser, thermometer, the heating electric mantle, then to wherein adding 250g 90% ethanol-water solution, start stirring, under agitation condition sequentially to wherein adding 16.8g (0.3mol) iron powder, 5.0g concentration is 36% hydrochloric acid, finish, build bottle stopper, open the reflux exchanger water coolant, open heating system, under agitation condition, system temperature is heated to and boils, keep being incubated under the boiling condition activation 30 minutes, then in 4.0 hours, evenly add 15g (0.078mol) 5-nitro-6-methyl benzimidazolone to system, fed in raw material once in per during this time 5 minutes, temperature maintains reflux state all the time, finish, reflux conditions continues insulation reaction 4.0h down, and insulation is finished, with yellow soda ash with the reaction solution PH=6.5-7.0 that neutralizes, continue to stir 10 minutes, stop then stirring, insulation sedimentation 20 minutes, filter with a B that is preheating near 100 ℃, iron mud is 90% alcohol reflux making beating 30 minutes with 200ml concentration, stops to stir insulation sedimentation 20 minutes then, filter, merge mother liquor and washing lotion, natural non-shock chilling is after cooling to room temperature, filter, products obtained therefrom is 50 ℃ of oven dry under infrared lamp, get the 11.2g product, purity 99.0%, outward appearance is faint yellow plate crystal, and yield is 87.2%.
Embodiment four:
Make 5-nitro-6-methyl benzimidazolone 133.8g, purity 99.2%, yield 98.2% by the method for embodiment two.
After the one 500ml autoclave that installs bottom insert canal cleaned; add the 250g 80%DMF-aqueous solution; 19.3g (0.10mol) 5-nitro-6-methyl benzimidazolone; 0.579g Ruan Shi nickel; be 3% of 5-nitro-6-methyl benzimidazolone weight; finish; build kettle cover; with nitrogen system is replaced 3 times under the 4atm condition; use hydrogen exchange then 3 times; after displacement finishes; system is charged into 5.0atm hydrogen; start stirring, under agitation condition, in 2.0 hours; slowly system temperature is raised to 100 ℃; and under this temperature insulation reaction 5.0 hours, insulation is finished, and stops heating; cool in 40 ℃; by bottom insert canal, feed liquid in the system is pressed in the there-necked flask of crossing with nitrogen replacement, then under nitrogen protection; with B the system inner catalyst is filtered out; product liquid returns there-necked flask and carries out underpressure distillation, and vacuum tightness should remain on more than the 0.98atm, and the system of distillation presents large-tonnage product and separates out; stop heating; with water-bath system is cooled in 25 ℃, then tail is connect nitrogen, with system emptying; Distallation systm is removed; under agitation condition, in 30 minutes, drip 150ml distilled water with dropping funnel to system; drip and finish; continue to stir and to separate out fully to product in 20 minutes, filter, on a small quantity cold water washing; after draining; 50 ℃ of oven dry under infrared lamp get product 15.1g, purity 99.1%; outward appearance is brown crystallization, yield 91.8%.
Embodiment five
Press the synthetic 5-nitro of method-6-methyl benzimidazolone 133.6g of embodiment one, purity 99.4%, yield 98.3%.
After the one 500ml autoclave that installs bottom insert canal cleaned; add the 250g 80%DMF-aqueous solution; 19.3g (0.10mol) 5-nitro-6-methyl benzimidazolone; 0.579g palladium-carbon catalyst; be 3% of 5-nitro-6-methyl benzimidazolone weight; finish; build kettle cover; with nitrogen system is replaced 3 times under the 4atm condition; use hydrogen exchange then 3 times; after displacement finishes; system is charged into 3.0atm hydrogen; start stirring, under agitation condition, in 2.0 hours; slowly system temperature is raised to 100 ℃; and under this temperature insulation reaction 3.0 hours, insulation is finished, and stops heating; cool in 40 ℃; by bottom insert canal, feed liquid in the system is pressed in the there-necked flask of crossing with nitrogen replacement, then under nitrogen protection; with B the system inner catalyst is filtered out; product liquid returns there-necked flask and carries out underpressure distillation, and vacuum tightness should remain on more than the 0.98atm, and the system of distillation presents large-tonnage product and separates out; stop heating; with water-bath system is cooled in 25 ℃, then tail is connect nitrogen, with system emptying; Distallation systm is removed; under agitation condition, in 30 minutes, drip 150ml distilled water with dropping funnel to system; drip and finish; continue to stir and to separate out fully to product in 20 minutes, filter, on a small quantity cold water washing; after draining; 50 ℃ of oven dry under infrared lamp get product 15.2g, purity 99.1%; outward appearance is the canescence crystallization, yield 92.4%.
Embodiment six:
Synthetic the 5-nitro-6-methyl benzimidazolone quality is 133.1g by the method for embodiment three, purity 99.3%, yield 97.8%.
Press the method for embodiment slender acanthopanax hydrogen reduction reaction, make solvent with 70% concentration DMF, the 17.37g palladium-carbon catalyst, be 90% of 5-nitro-6-methyl benzimidazolone weight, get 5-amino-6-methyl benzimidazolone product 14.5g, content 99.3%, outward appearance is faint yellow crystallization, yield 88.3%.
Embodiment seven:
Press the method for embodiment slender acanthopanax hydrogen reduction reaction, make solvent, get 5-amino-6-methyl benzimidazolone product 14.8g with 90% concentration DMF, content 99.2%, outward appearance is the white plates crystallization, yield 90.1%.
Claims (5)
1. the preparation method of 5-amino-6-methyl benzimidazolone is characterized in that in turn including the following steps:
(1) with 3, the 4-diaminotoluene carries out condensation with urea, preparation 5-methyl benzimidazolone;
(2) with the 5-methyl benzimidazolone, under rare nitric acid condition, carry out nitration reaction, make 5-nitro-6-methyl benzimidazolone;
(3) 5-nitro-6-methyl benzimidazolone passes through reduction reaction again, makes target compound 5-amino-6-methyl benzimidazolone;
The used solvent of step (1) condensation is an orthodichlorobenzene;
The used temperature of step (1) is 130-185 ℃;
The used temperature of step (2) nitration reaction is 25-30 ℃;
The used reduction mode of step (3) is iron powder reducing or hydrogenating reduction.
2. the preparation method of a kind of 5-amino as claimed in claim 1-6-methyl benzimidazolone is characterized in that the solvent that the iron powder reducing process is adopted is an ethanol-water system, and ethanol quality percentage composition is 80-90% in this system.
3. the preparation method of a kind of 5-amino as claimed in claim 1-6-methyl benzimidazolone is characterized in that the solvent that hydrogenating reduction adopts is the DMF-aqueous systems, and the DMF weight content is 70-90% in this system.
4. as the preparation method of claim 1 or 3 described a kind of 5-amino-6-methyl benzimidazolones, it is characterized in that the catalyzer that hydrogenating reduction adopts is Ruan Shi nickel or palladium carbon.
5. the preparation method of a kind of 5-amino as claimed in claim 4-6-methyl benzimidazolone is characterized in that the catalyst levels that is fit to is to be not less than 3% of 5-amino-6-methyl benzimidazolone weight.
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| CN102295605B (en) * | 2011-06-22 | 2014-07-23 | 华东理工大学 | Method for preparing benzimidazolone derivative |
| CN107365273B (en) * | 2017-08-11 | 2020-01-24 | 东营市天正化工有限公司 | Production method for synthesizing 5-nitrobenzimidazole ketone by one-pot method |
| CN109627219A (en) * | 2018-12-29 | 2019-04-16 | 高邮市华宝颜料有限公司 | A kind of production method of 5- amino-6-methyl benzimidazolone |
| CN110256435A (en) * | 2019-07-04 | 2019-09-20 | 绍兴市精益生物化工有限公司 | One-step synthesis method of 1, 3-dimethyl uric acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6087480A (en) * | 1998-01-13 | 2000-07-11 | Ciba Specialty Chemcals Corporation | Process for preparing sparingly soluble aromatic amines |
| CN1675185A (en) * | 2002-06-07 | 2005-09-28 | 科蒂科股份有限公司 | Therapeutic molecules and methods-1 |
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| US6087480A (en) * | 1998-01-13 | 2000-07-11 | Ciba Specialty Chemcals Corporation | Process for preparing sparingly soluble aromatic amines |
| CN1675185A (en) * | 2002-06-07 | 2005-09-28 | 科蒂科股份有限公司 | Therapeutic molecules and methods-1 |
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