CN85101310A - 3,4, the method for making of 5-trimethoxy-benzonitrile - Google Patents
3,4, the method for making of 5-trimethoxy-benzonitrile Download PDFInfo
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- CN85101310A CN85101310A CN198585101310A CN85101310A CN85101310A CN 85101310 A CN85101310 A CN 85101310A CN 198585101310 A CN198585101310 A CN 198585101310A CN 85101310 A CN85101310 A CN 85101310A CN 85101310 A CN85101310 A CN 85101310A
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- 238000000034 method Methods 0.000 title claims abstract description 39
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 title claims abstract description 37
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000002253 acid Substances 0.000 claims abstract description 15
- 239000004202 carbamide Substances 0.000 claims abstract description 15
- SJSOFNCYXJUNBT-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC(OC)=C1OC SJSOFNCYXJUNBT-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- IWPZKOJSYQZABD-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Natural products COC1=CC(OC)=CC(C(O)=O)=C1 IWPZKOJSYQZABD-UHFFFAOYSA-N 0.000 claims abstract description 7
- OSBQUSPVORCDCU-UHFFFAOYSA-N 3,4,5-trimethoxybenzonitrile Chemical compound COC1=CC(C#N)=CC(OC)=C1OC OSBQUSPVORCDCU-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- 239000011541 reaction mixture Substances 0.000 claims description 11
- 239000007864 aqueous solution Substances 0.000 claims description 6
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- 238000009835 boiling Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical group COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000001983 dialkylethers Chemical class 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N anhydrous diethylene glycol Natural products OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- -1 arene compound Chemical class 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000002923 oximes Chemical class 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 3
- JSZOAYXJRCEYSX-UHFFFAOYSA-N 1-nitropropane Chemical compound CCC[N+]([O-])=O JSZOAYXJRCEYSX-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 150000002611 lead compounds Chemical class 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 229940019778 diethylene glycol diethyl ether Drugs 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 235000012204 lemonade/lime carbonate Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960001082 trimethoprim Drugs 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention relates to by 3,4,5-trimethoxybenzoic acid preparation 3,4, the method for 5-trimethoxy-benzonitrile, it comprises that with 3,4 5-trimethoxybenzoic acid and urea and thionamic acid react, and isolates 3,4 of generation then, 5-trimethoxy-benzonitrile.
3,4,5-trimethoxy-benzonitrile is a chemical industry, particularly known important intermediates in the pharmaceutical industry.The advantage of the inventive method is to be easy to industrializing implementation, less investment, productive rate height.
Description
The present invention is preparation 3,4, a kind of new improving one's methods of 5-trimethoxy-benzonitrile.
3,4, the 5-trimethoxy-benzonitrile is a chemical industry, particularly a kind of known intermediates in the pharmaceutical industry.For example, it can be used for Synthetic 2,4-diamino-5-(3,4,5-trimethoxy benzyl)-pyrimidine (being Trimethoprim BP), this product is a kind of well-known antiseptic-germicide and Trimpex.3,4, the 5-trimethoxy-benzonitrile can also be used for 3,4 of the industrial generally use of manufacturing chemistry, 5-TMB.3,4, the 5-TMB is a kind of compound of difficult acquisition, normally by 3,4, the preparation of 5-trimethoxy-benzonitrile.
3,4, the method for making of 5-trimethoxy-benzonitrile is known several.One of them is with 3,4, and the 5-trimethoxybenzoic acid is a raw material, in accordance with known methods, makes 3,4, and 5-trimethoxybenzoic acid and sulfur oxychloride effect obtain 3,4, the 5-trimethoxy-benzoyl chloride.Make 3,4 again, 5-trimethoxy-benzoyl chloride and ammonium hydroxide reaction are converted into 3,4, the 5-trimethoxy-benzamide.This acid amides promptly generates 3,4 with the phosphorus oxychloride dehydration, the 5-trimethoxy-benzonitrile (" organic chemistry 》 Za Chi the 24th volume, the 387th page of nineteen fifty-nine) (J.Org.Chem24,387(1959)).The shortcoming of aforesaid method is that reaction must be through three steps, and need isolate intermediate product.A step that generates acyl chlorides in three steps will be used the sulfur oxychloride of deep-etching, therefore, will produce the variety of problems that equipment and materials is selected in suitability for industrialized production.The overall yield of these three reactions is a medium level.According to another currently known methods, 3,4, after together heating, the plumbous rhodanate of 5-trimethoxybenzoic acid and equivalent changes 3,4 into, the 5-trimethoxy-benzonitrile.The shortcoming of this method is that used lead compound has very strong toxicity, and produces hydrogen sulfide in reaction.This method also should not be used for plant-scale production, because it can cause environmental pollution and insalubrity (" German chemical Hui Chi " the 38th volume, the 3635th page) (Berichte 38,3635).Another production method (German pharmacy meeting Chi of association, 1934,277 phases, 221～223 pages) (Berichte der deutschen pharmazeutis-chen Gesellschaft 277,221～223(1934)) be with 3,4,5-trimethoxybenzoic acid and sulphur hydracid lead are 200 ℃ of together heating.This method has the shortcoming identical with last method, owing to used supervirulent lead compound, also should not be used for plant-scale production.In the above referred-to references, all do not speak of productive rate.
Also have much 3,4 in addition, the method for making of 5-trimethoxy-benzonitrile adopts 3,4, and the 5-TMB is a starting raw material.One of them is with 3,4, and the 5-TMB changes corresponding oxime into, and again with 3,4 of gained, the acetic anhydride of 5-TMB oxime and 10 times of amounts together is heated to and boils.This method shortcoming is that 3,4, it is that water electrode is responsive severe corrosive methodology that 5-TMB oxime heats in acetic anhydride.Therefore when being used for plant-scale production, will face the selection problem of equipment and materials, and the cost height.Do not speak of the productive rate (German chemical Hui Chi, 41 volumes, 1921 pages) (Berichte 41,1921) in each step in the document yet.Report (" U.S. state chemistry Hui Chi " 83 volumes in 1961,2203 pages according to other documents; Austria's " chemist's newspaper ", 1962 63 volumes (6), 177～182 pages) (J.Am.Chem Soc83,2203/1961/; Sterr.Chemiker.Zeitung63, (6), 177～182(1962)) 3,4, the 5-TMB is reacted with nitropropane and Secondary ammonium phosphate in the Glacial acetic acid medium, generates 3,4, and 5-trimethoxy-benzonitrile, productive rate are 74%.This reaction needs to carry out the long period (16 hours) under the reflux condition.The shortcoming of this method is, the aggressiveness of reaction medium Glacial acetic acid and corrodibility are very big, and in addition, nitropropane is explosive Hazardous substances, is difficult to handle.
In sum, we can say that with 3,4, the 5-TMB is made 3,4 of raw material, the industrial-scale production of 5-trimethoxy-benzonitrile, except above-mentioned various shortcoming was arranged, its diseconomy was that also 3 is a kind of rare material.With 3,4, the 5-trimethoxybenzoic acid be raw material can be economically, with industrial-scale production 3,4, the 5-trimethoxy-benzonitrile.Yet known is that the method for making of raw material is not suitable for industrial-scale production with it, and its reason went through in front.
The objective of the invention is, overcome existing preparation method's various defectives, work out a kind ofly with 3,4, the 5-trimethoxybenzoic acid is that raw material can be economically with industrial-scale production 3,4, the method for 5-trimethoxy-benzonitrile.
The invention provides a kind of by 3,4,5-trimethoxybenzoic acid preparation 3,4, the method for 5-trimethoxy-benzonitrile.This method comprises that with 3,4 5-trimethoxybenzoic acid and urea and thionamic acid react, and isolates 3,4 of generation then, the 5-trimethoxy-benzonitrile.
The present invention is based on following understanding, and with 3,4, it is required 3,4 that the reaction of 5-trimethoxybenzoic acid and urea and thionamic acid can generate in a step, the 5-trimethoxy-benzonitrile, and productive rate might as well.
Thionamic acid both can be directly used in reaction, also can make in reaction mixture, continued reaction in former reactor.
Specific practice of the present invention is with 1 mol 3,4,5-trimethoxybenzoic acid and 1.5～2.5 mol urea and the reaction of 1.5～3.0 mol thionamic acids.Better with 2 mol urea and 2.0～2.5 mol thionamic acid reaction results.Reaction can be carried out when temperature is 190～210 ℃, particularly carries out better in the time of about 200 ℃.Reaction need be carried out several hrs, and the general reaction times is 3～5 hours.
Be preferably in the reaction mixture and add a kind of boiling point and be higher than 200 ℃ solvent.For this reason, should select an alkyl or dialkyl ether (for example, diethylene glycol dimethyl ether or diethylene glycol diethyl ether), dibasic alcohol (for example, propylene glycol) or the naphthane of two (aliphatic dialcohols) for use.Proved and selected Diethylene Glycol-methyl ether particularly advantageous for use.
Implementing another way of the present invention, is with urea and chlorsulfonic acid prepared in reaction thionamic acid.Reaction can be carried out being heated under about 100 ℃ condition, after gas to be no longer included is emitted, adds 3,4 in this reactant, the 5-trimethoxybenzoic acid.React under 190～210 ℃, preferable temperature of reaction is about 200 ℃ again.In this reaction, 1 mol 3,4, the 5-trimethoxybenzoic acid can be with 2.5～3.5 molar urea and 1.5～3.0 molar chlorsulfonic acids.Proportioning is 1 mol 3,4 preferably, and the 5-trimethoxybenzoic acid is with 3 mol urea and 1.5～2.5 mol chlorsulfonic acids.
Reaction mixture can adopt several method to handle.A kind of is with alkalization (for example adding alkali metal hydroxide aqueous solution) then in the reaction mixture impouring water.Inorganic salts and unreacted 3,4, the 5-trimethoxybenzoic acid dissolves in the aqueous solution, be settled out 3,4, the 5-trimethoxy-benzonitrile can be with filtering or centrifugal separation is separated.Another kind method be with suitable solvent (for example toluene) 3,4, the 5-trimethoxy-benzonitrile extracts, and evaporates the extraction liquid of gained then.
With the inventive method make 3,4, the 5-trimethoxy-benzonitrile generally can be used for multiple reaction and need not pass through any purge process.But the method that also can adopt recrystallization when needing is purified (as available recrystallizing methanol).
Implementing better mode of the present invention, is to isolate 3,4, and behind the 5-trimethoxy-benzonitrile, the aqueous solution that acidifying is left is to reclaim 3,4, the 5-trimethoxybenzoic acid.Mineral acid (example hydrochloric acid) is preferably used in acidifying.3,4 of recovery, 5-trimethoxybenzoic acid can be reused for preparation 3,4,5-trimethoxy-benzonitrile.
The advantage of the inventive method is, it can technical scale be implemented, and expense is few, the productive rate height.
Can further understand the present invention from following several examples, but this and do not mean that claimed scope only limits to these listed examples.
Example 1
In 125 kilograms of 140 ℃ of fusions (0.59 kilogram of molecule) 3,4, the mixture of 5-trimethoxybenzoic acid, 71 kilograms of (1.18 kilograms of molecules) urea and 144 kilograms of (1.48 kilograms of molecules) thionamic acids is warmed up to 190 ℃ then.Stirred reaction mixture is 2 hours under this temperature.Add 90 liters of Diethylene Glycol-methyl ethers, the temperature with reaction mixture rises to 190 ℃ again, and keeps this temperature to continue to stir 2 hours.
In reaction mixture impouring 1000 premium on currency, gained suspension is cooled to 20 ℃, add 670 kilogram 25% aqueous sodium hydroxide solution again.Inorganic salts and unreacted 3,4, the 5-trimethoxybenzoic acid enters water.The suspension that centrifugation forms can obtain 95 kilogram 3,4, and 5-trimethoxy-benzonitrile, productive rate are 83.5%.Fusing point: 90 ℃.After recrystallizing methanol, get 3,4,76.5 kilograms of 5-trimethoxy-benzonitriles, productive rate are 67.22%.Fusing point: 94 ℃.
Alkaline mother liquor after the centrifugation is heated to boiling, is cooled to 40～50 ℃ again, transfer pH to 1 with concentrated hydrochloric acid.Gained suspension is cooled to 0～5 ℃, be settled out 3,4, the 5-trimethoxybenzoic acid separates with centrifuging, and the washing disacidify.Can get like this 50 kilograms wet 3,4, the 5-trimethoxybenzoic acid.Add 200 liters in water in this product, form suspension, in this suspension, add 25 liters of ammonium hydroxide aqueous solutions and dissolve fully until product.Filter or centrifugation gained solution and regulate pH value of filtrate with concentrated hydrochloric acid.Be precipitated out 3,4, the 5-trimethoxybenzoic acid separate with centrifuging and the washing disacidify dry then, can obtain 25 kilogram 3,4 like this, the 5-trimethoxybenzoic acid; This acid can be reused for 3,4, the production of 5-trimethoxy-benzonitrile.Reacted 3,4, be converted into 3,4 in the 5-trimethoxybenzoic acid, the transformation efficiency of 5-trimethoxy-benzonitrile is 84.0%(herein 3,4, the 5-trimethoxy-benzonitrile is the product through recrystallization).
Example 2
With 396 gram (6.6 mol) urea, 639 gram (6.59 mol) thionamic acids and 700 gram (3.30 mol) 3,4, the mixture of 5-trimethoxybenzoic acid was 190 ℃ of heating 4 hours.Again this reaction mixture is cooled to room temperature and to wherein adding 1.5 premium on currency, 5 liters of toluene and 100 gram lime carbonate.3,4 of generation, the 5-trimethoxy-benzonitrile enters the toluene phase.In 100 ℃ of reacting by heating mixtures 20 minutes, be cooled to room temperature again, to wherein adding 200 milliliters of dense ammonium hydroxide aqueous solutions and 25 gram gacs.Filter, filtrate is divided into organic layer and water layer.Evaporation toluene phase is suspended in residuum in 1.5 liters of acetone under vacuum condition, and adds 25 gram gacs, and is warm and filter this mixture.Filtrate is under agitation injected water, leaches and drying precipitated product.Can get 3,4 like this, 5-trimethoxy-benzonitrile 510 grams, productive rate is 80%.Fusing point: 93 ℃.
Under agitation in filtrate, add concentrated hydrochloric acid and regulate pH value to 2.Leave standstill this mixture, leach sedimentary product then, and it is dry again to be washed to neutrality.Can get 3,4 like this, 5-trimethoxybenzoic acid 35 grams, this acid can be reused for preparation 3,4,5-trimethoxy-benzonitrile.Reacted 3,4, be converted into 3,4 in the 5-trimethoxybenzoic acid, the transformation efficiency of 5-trimethoxy-benzonitrile is 84.3%.
Example 3
In stirring, water cooling and be lower than and in 18.0 gram (0.3 mol) urea, splash into 20.4 gram (0.18 mol) chlorsulfonic acids under 50 ℃ the condition.With this mixture heating up to 100 ℃ and be stirred under this temperature no longer include gas and emit till.Add 21.2 gram (0.10 mol) 3,4,5-trimethoxybenzoic acid and 190～200 ℃ of following stirred reaction mixtures 4 hours.Then it is cooled to room temperature and adds 100 milliliter 10% sodium hydroxide solution.Filter the suspension that forms, product is washed dry then on strainer.So can get 15 grams 3,4,5-trimethoxy-benzonitrile, productive rate are 77.7%.Fusing point: 92 ℃.Thick product with recrystallizing methanol after, can get 12.5 grams 3,4,5-trimethoxy-benzonitrile, productive rate are 64.7%.Fusing point: 94 ℃.
3,4, the 5-trimethoxybenzoic acid can reclaim (4.5 gram) by the method for example 1 from filtrate.Reacted 3,4, be converted into 3,4 in the 5-trimethoxybenzoic acid, the transformation efficiency of 5-trimethoxy-benzonitrile is 82.2%.(recrystallization cross 3,4, the 5-trimethoxy-benzonitrile).
Claims (11)
1, by 3,4,5--trimethoxybenzoic acid preparation 3,4, the method for 5--trimethoxy-benzonitrile, its feature comprises; With 3,4,5--trimethoxybenzoic acid and urea and thionamic acid reaction are isolated 3,4 of generation, the 5--trimethoxy-benzonitrile then.
2, as claim 1 described method, its feature comprises, makes thionamic acid with chlorsulfonic acid and urea situ reaction.
3, as claim 1 described method, its feature comprises that carrying out this reaction between 190 ℃ to 210 ℃ needs 3 to 5 hours.
4, as claim 2 described methods, its feature comprises that carrying out this reaction between 190 ℃ to 210 ℃ needs 3 to 5 hours.
5, as claim 1 described method, its feature comprises, for 1 molar 3,4, the 5-trimethoxybenzoic acid uses 1.5 to 2.5 mol, is preferably 2 mol, urea and 1.5 to 3.0 mol, be preferably 2.0 to 2.50 mol, thionamic acid.
6, as claim 2 described methods, its feature comprises, for 1 molar 3,4, the 5-trimethoxybenzoic acid uses 2.5 to 3.5 mol, is preferably 3 mol, urea and 1.5 to 3.0 mol, be preferably 1.5 to 2.5 mol, chlorsulfonic acid.
7, as claim 1 described method, its feature comprises, adds boiling point and be higher than 200 ℃ solvent in said reaction mixture, preferably adds the ether or the arene compound of alkyl of Diethylene Glycol or dialkyl ether, dibasic alcohol, dibasic alcohol.
8, as claim 7 described methods, its feature comprises, it is Diethylene Glycol-methyl ether that used boiling point is higher than 200 ℃ solvent.
9, as claim 1 described method, its feature comprises, adopt following step to separate 3,4,5-trimethoxy-benzonitrile: with the inorganic salts in the reaction mixture and unreacted 3,4, the 5-trimethoxybenzoic acid is dissolved in the aqueous solution of alkali metal hydroxide, tell 3,4, the 5-trimethoxy-benzonitrile with filtration or centrifugal separation then.
10, as claim 1 described method, its feature comprises, 3,4, and the separation of 5-trimethoxy-benzonitrile is to use a kind of suitable solvent (preferably toluene) to extract, and evaporates this extraction liquid then.
11, as each described method in 1 to 10 of the claim, its feature comprises, with 3,4, after the 5-trimethoxy-benzonitrile filtering separation, the resulting filter liquor that contains of acidifying, be settled out 3,4, the 5-trimethoxybenzoic acid is separated, and reuses.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU834438A HU191909B (en) | 1983-12-23 | 1983-12-23 | Process for production of 3,4,5-trimetoxi-benzonitril |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN85101310A true CN85101310A (en) | 1987-01-24 |
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ID=10967960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN198585101310A Pending CN85101310A (en) | 1983-12-23 | 1985-04-01 | 3,4, the method for making of 5-trimethoxy-benzonitrile |
Country Status (17)
| Country | Link |
|---|---|
| JP (1) | JPS60214767A (en) |
| CN (1) | CN85101310A (en) |
| BE (1) | BE901284A (en) |
| CH (1) | CH660730A5 (en) |
| CS (1) | CS1024484A2 (en) |
| DE (1) | DE3446871A1 (en) |
| ES (1) | ES8600735A1 (en) |
| FI (1) | FI845107L (en) |
| FR (1) | FR2557106A1 (en) |
| GB (1) | GB2151626B (en) |
| HU (1) | HU191909B (en) |
| IT (1) | IT1178793B (en) |
| NL (1) | NL8403885A (en) |
| PL (1) | PL251144A1 (en) |
| RO (1) | RO92934B (en) |
| SE (1) | SE8406578L (en) |
| SU (1) | SU1452477A3 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103772236A (en) * | 2014-01-15 | 2014-05-07 | 华侨大学 | Preparation method of cyanobenzene derivative |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH494210A (en) * | 1968-03-27 | 1970-07-31 | Sandoz Ag | Process for the production of nitriles |
| JPS5476544A (en) * | 1977-11-26 | 1979-06-19 | Sumitomo Chem Co Ltd | Preparation of p-cyanophenol |
| JPS5495541A (en) * | 1978-01-06 | 1979-07-28 | Sumitomo Chem Co Ltd | Production of cyanophenol |
-
1983
- 1983-12-23 HU HU834438A patent/HU191909B/en not_active IP Right Cessation
-
1984
- 1984-12-17 BE BE1/11154A patent/BE901284A/en not_active IP Right Cessation
- 1984-12-20 CH CH6072/84A patent/CH660730A5/en not_active IP Right Cessation
- 1984-12-21 ES ES538924A patent/ES8600735A1/en not_active Expired
- 1984-12-21 CS CS8410244A patent/CS1024484A2/en unknown
- 1984-12-21 DE DE19843446871 patent/DE3446871A1/en not_active Withdrawn
- 1984-12-21 JP JP59268716A patent/JPS60214767A/en active Pending
- 1984-12-21 IT IT24230/84A patent/IT1178793B/en active
- 1984-12-21 SE SE8406578A patent/SE8406578L/en not_active Application Discontinuation
- 1984-12-21 RO RO116816A patent/RO92934B/en unknown
- 1984-12-21 FR FR8419641A patent/FR2557106A1/en active Pending
- 1984-12-21 PL PL25114484A patent/PL251144A1/en unknown
- 1984-12-21 SU SU847773698A patent/SU1452477A3/en active
- 1984-12-21 FI FI845107A patent/FI845107L/en not_active Application Discontinuation
- 1984-12-21 GB GB08432498A patent/GB2151626B/en not_active Expired
- 1984-12-21 NL NL8403885A patent/NL8403885A/en not_active Application Discontinuation
-
1985
- 1985-04-01 CN CN198585101310A patent/CN85101310A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103772236A (en) * | 2014-01-15 | 2014-05-07 | 华侨大学 | Preparation method of cyanobenzene derivative |
| CN103772236B (en) * | 2014-01-15 | 2016-04-13 | 华侨大学 | A kind of preparation method of benzonitrile derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| CH660730A5 (en) | 1987-06-15 |
| IT1178793B (en) | 1987-09-16 |
| ES538924A0 (en) | 1985-11-01 |
| GB2151626A (en) | 1985-07-24 |
| PL251144A1 (en) | 1985-10-08 |
| JPS60214767A (en) | 1985-10-28 |
| RO92934A (en) | 1987-12-31 |
| CS1024484A2 (en) | 1988-07-15 |
| HU191909B (en) | 1987-04-28 |
| SU1452477A3 (en) | 1989-01-15 |
| FR2557106A1 (en) | 1985-06-28 |
| SE8406578L (en) | 1985-06-24 |
| FI845107L (en) | 1985-06-24 |
| FI845107A0 (en) | 1984-12-21 |
| GB8432498D0 (en) | 1985-02-06 |
| BE901284A (en) | 1985-06-17 |
| RO92934B (en) | 1988-01-01 |
| SE8406578D0 (en) | 1984-12-21 |
| ES8600735A1 (en) | 1985-11-01 |
| HUT36085A (en) | 1985-08-28 |
| GB2151626B (en) | 1987-04-29 |
| IT8424230A0 (en) | 1984-12-21 |
| NL8403885A (en) | 1985-07-16 |
| DE3446871A1 (en) | 1985-07-11 |
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Correct: Tang Yue False: Tang Yue Number: 6 Page: 28 Volume: 3 |
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| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |