CN108059605A - The synthetic method of p-aminophenyl formonitrile HCN - Google Patents
The synthetic method of p-aminophenyl formonitrile HCN Download PDFInfo
- Publication number
- CN108059605A CN108059605A CN201711390502.XA CN201711390502A CN108059605A CN 108059605 A CN108059605 A CN 108059605A CN 201711390502 A CN201711390502 A CN 201711390502A CN 108059605 A CN108059605 A CN 108059605A
- Authority
- CN
- China
- Prior art keywords
- formonitrile hcn
- catalyst
- aminophenyl
- synthetic method
- cuprous
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 0 *C1C=CC(C(*)(*)*)=CC1 Chemical compound *C1C=CC(C(*)(*)*)=CC1 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of synthetic methods of p-aminophenyl formonitrile HCN, using to halogenated trihalomethyl group benzene or to trihalomethyl group aniline as starting material or intermediate, in alcohol and water mixture is molten, adduction enters aminating agent, by catalyst, co-catalyst at 100 ~ 250 DEG C, catalytic reaction under 1.0 ~ 10.0MPa, reaction product is through the isolated p-aminophenyl nitrile of rectifying.After being synthesized using this method, by gas boosting pumped excess of ammonia, compressed condensation becomes liquefied ammonia, synthesizes material separation of solid and liquid after precipitation, and liquid material is rectifying to obtain p-aminophenyl nitrile.Being evaporated before the liquefied ammonia of recycling and the recycling design of precipitation, rectifying can be recycled and reused for feeding intake.High using this technique productions raw materials ammonia utilization rate, no technique waste water is environmentally friendly.
Description
Technical field
The present invention relates to a kind of synthetic methods of p-aminophenyl formonitrile HCN.
Background technology
P-aminophenyl nitrile is used as synthesis multi-medicament and material, as radioprotectant, it used also as aldose, ketose and
Derivative reagent in the capillary zone electrophoresis analysis of uronic acid, synthesis liquid crystal material, essence.In addition, it is used to prepare containing side
The methacrylic acid monomer of chain azobenzene structure and polythiophene in the side chain containing azobenzene part.The drug of synthesis is as synthesized
Bicalutamide (morning sunlight), etravirine, up to than adding alcohol ester.1. Bicalutamide：Drug trade name " morning sunlight is first ", belongs to nonsteroidal
Antiandrogen drug, the treatment applied to advanced prostate cancer.
2. etravirine：It is the non-nucleoside reverse transcriptase of new generation inhibition of subordinate Tibotec companies of Johson ＆ Johnson exploitation
Agent (NNRTIs), in January, 2008 are ratified to list through U.S. FDA, become the weight of highly effective antiretroviral therapy (HAART) drug
Want one of component.Clinically huge contribution has been made to reduce the morbidity and mortality of AIDS.
3. up to than adding alcohol ester：Clinically reach than adding the oral anticoagulation object of new generation that alcohol ester is forefront, direct fibrin ferment
Inhibitor (DTIs), for the palsy and systemic embolism of medicine for preventing nonvalvular atrial patient.
4. United States Patent (USP) US 2013/0217762A1SELECTIVE ANDROGEN RECEPTOR MODULATORS, hair
Understand a kind of new using p-aminophenyl nitrile as the selective androgen receptor modulators and its salt and pharmaceutical composition of Material synthesis.
Claim to provide the noval chemical compound as AR agonists according to inventor.Such noval chemical compound can be solved to muscular atrophy, sexual gland
The needs that hypofunction or cachexia are effectively treated minimize forefront hylperadenosis or the risk of HDL reductions.
According to related data, p-aminophenyl nitrile synthetic method has to halogenated aniline cyaniding, to halogenated benzonitrile amination, to amino
Benzamide dehydration p-nitrophenyl nitrile reduction etc..Domestic current industrial production method is：Para Amino Benzamide is molten in toluene etc.
In agent, the dehydration under the effect of phosphorus pentoxide, thionyl chloride, phosphorus oxychloride or phosphorus pentachloride, then acidified, decoloration, alkali
It washes, be refining to obtain product, a large amount of acid, alkaline waste waters and phosphorus-containing wastewater or sulfur-containing waste water, exhaust gas are generated in production process.It is former
Expect Para Amino Benzamide synthesis, also to pass through nitrification, chloride, condensation, reduction, the similary a large amount of phosphorous sulfur-containing waste waters of generation give up
Gas.Chinese patent application publication No.：CN105753738A, proposition is a kind of to be used in catalyst Pd/SnO2- by p-nitrobenzonitfile
The technique of the lower hydrogenating reduction of Sb2O3 catalysis, this method catalyst is expensive, and preparation method is complicated, and does not refer to that catalyst makes
With the service life, and its general synthetic method of raw material p-nitrobenzonitfile is by paranitrobenzoic acid and para toluene sulfonamide reaction system
, paranitrobenzoic acid, the synthesis of para toluene sulfonamide or both Material synthesis p-nitrobenzonitfiles can all generate
Spent acid or sulfur-containing waste water exhaust gas.
The content of the invention
It is an object of the invention to provide it is a kind of solve to generate phosphorous or sulfur-containing waste water in current production technology, exhaust gas is asked
The synthetic method for the p-aminophenyl nitrile that topic, raw material are easy to get.
The present invention technical solution be：
A kind of synthetic method of p-aminophenyl formonitrile HCN, it is characterized in that：With to halogenated trihalomethyl group benzene or to three halogenated first
Base aniline is starting material or intermediate, and in alcohol and water mixture is molten, adduction enters aminating agent, is existed by catalyst, co-catalyst
100~250 DEG C, catalytic reaction under 1.0~10.0MPa, reaction product is through isolated p-aminophenyl formonitrile HCN (its chemical formula of rectifying
For)。
After catalytic reaction, less than 50 DEG C are cooled to, release, when release starts gas boosting pump, by excess of ammonia pressure
It contracts, be condensed into liquefied ammonia for feeding intake；It lets out after unloading and being depressed into normal pressure, material is transferred to normal-pressure reaction kettle removing solvent, is then demultiplex out
Catalyst residue, liquid material rectifying separation, obtains p-aminophenyl formonitrile HCN.
It is described to halogenated trihalomethyl group benzene, general formula isIn formula R for fluorine, chlorine, bromine, iodine or
Any one of amido, X, Y, Z are any one of fluorine, chlorine, bromine, iodine or amido or arbitrary different combination, such as to chlorine
Benzotrifluoride, p-chlorotrichlormethyl, to one toluene fluoride of bromine dichloro, p-trifluoromethylaniline etc., preferably p-chloro benzo trifluoride-99, to chlorine
Benzotrichloride and p-trifluoromethylaniline.
The catalyst is the combination of cuprous salt or cuprous salt and co-catalyst.
The cuprous salt is in stannous chloride, cuprous cyanide, copper fluoride, cuprous bromide, cuprous iodide, cuprous sulfate
One or more of combinations；Co-catalyst is the combination of potassium fluoride or highly basic or highly basic and potassium fluoride.
Highly basic described in co-catalyst is inorganic base.
The alcohol is methanol or ethyl alcohol.
The aminating agent is ammonium hydroxide or ammonia；Molar ratio to halogenated trihalomethyl group benzene and aminating agent is 1:3~1:20.
After being synthesized using this method, by gas boosting pumped excess of ammonia, compressed condensation becomes liquefied ammonia, closes
Into material, separation of solid and liquid, liquid material are rectifying to obtain p-aminophenyl nitrile after precipitation.The recycling of the liquefied ammonia and precipitation of recycling is molten
Being evaporated before agent, rectifying can be recycled and reused for feeding intake.High, no technique waste water, to environment using this technique productions raw materials ammonia utilization rate
It is friendly.
Description of the drawings
Fig. 1 is the infrared spectrogram of synthetic product Structural Identification of the present invention.
Fig. 2 is the gas chromatography mass spectrometry TIC figures of synthetic product Structural Identification of the present invention and mass spectrum retrieval result
Fig. 3 is the nuclear magnetic resonance spectroscopy of synthetic product Structural Identification of the present invention.
Fig. 4 is the carbon-13 nmr spectra of synthetic product Structural Identification of the present invention.
It is p-aminophenyl nitrile to identify product of the present invention.
Specific embodiment
Embodiment 1：
P-chloro benzo trifluoride-99 245 grams (99.0%, 1.343mol) is added in 1000ml autoclaves, adds in absolute ethyl alcohol 200
Gram, 20 grams of water adds in 20 grams of stannous chloride, 30 grams of potassium fluoride.Enclosed high pressure kettle, with nitrogen displacement three times after, be passed through liquefied ammonia 140
(99.6%, 8.202mol) gram.Starting stirring, be warming up to 170~180 DEG C, pressure rises to 6.0~7.5MPa, 170~
When 180 DEG C of heat preservations 12 are small.Heat preservation terminates, and is cooled to 30 DEG C, crack pressure-relief valve release, and gas uses gas after B-grade condensation during release
The compression of body booster pump, condensation enter high pressure storage tank.Release (booster pump pumping) stops being pressurized to after pressure -0.02MPa or so in kettle
Pumping gas opens autoclave, material is transferred in 1000ml four-hole bottles, and heat up precipitation, is finally warming up to 95 DEG C, no fraction steams
After going out, 60 DEG C or so are cooled to, is filtered, obtains 218.6 grams of liquid material, gas spectrum detection, p-aminophenyl nitrile content 3.12%, to three
Methyl fluoride aniline 33.9%, generation p-aminophenyl nitrile molar yield 4.30%.Rectification under vacuum obtains 6.1 grams of faint yellow solid, melts
83.2 DEG C of point, p-aminophenyl nitrile content 98.6%.
Embodiment 2：
P-chloro benzo trifluoride-99 245 grams (99.0%, 1.343mol) is added in 1000ml autoclaves, adds in absolute ethyl alcohol 200
Gram, 20 grams of water adds in 20 grams of stannous chloride, 20 grams of potassium fluoride, 40 grams of potassium hydroxide.Enclosed high pressure kettle, with nitrogen displacement three times
Afterwards, it is passed through liquefied ammonia 160 (99.6%, 9.374mol) gram.Starting stirring, be warming up to 170~180 DEG C, pressure rises to 6.0~
8.5MPa, when 170~180 DEG C of heat preservations 15 are small.Heat preservation terminates, and if example 1 operates, filters, obtains 205.9 grams of liquid material, gas
Spectrum detection, p-aminophenyl nitrile content 35.53%, p-trifluoromethylaniline 10.97% generate p-aminophenyl nitrile molar yield
42.43%.Rectification under vacuum obtains 61.6 grams of faint yellow solid, 83.8 DEG C of fusing point, p-aminophenyl nitrile content 98.9%.
Embodiment 3：
P-chloro benzo trifluoride-99 85 grams (99.0%, 0.66mol) is added in 1000ml autoclaves, adds in 200 grams of ethyl alcohol of recycling
(ethyl alcohol 85.5%, water 11.5%, p-chloro benzo trifluoride-99 2.6%), evaporates 157 grams of (p-chloro benzo trifluoride-99s 75.5%, to three before rectifying
Methyl fluoride aniline 23.2%, p-aminophenyl nitrile 1.2%) 30 grams of absolute ethyl alcohol, (207.9 grams of p-chloro benzo trifluoride-99 of input is amounted to,
1.151mol；36.4 grams, 0.226mol of p-trifluoromethylaniline adds up to 1.377mol), add in 20 grams of stannous chloride, potassium fluoride
20 grams, 40 grams of potassium hydroxide.Enclosed high pressure kettle, with nitrogen displacement three times after, be passed through 160 grams of liquid ammonia recovery.Start stirring, heating
To 170~180 DEG C, pressure rises to 6.5~9.2MPa, when 170~185 DEG C of heat preservations 16 are small.Heat preservation terminates, as example 1 is grasped
Make, filter, obtain 210.7 grams of liquid material, gas spectrum detection, p-aminophenyl nitrile content 38.18%, p-trifluoromethylaniline
8.50%, p-chloro benzo trifluoride-99 and p-trifluoromethylaniline turn p-aminophenyl nitrile total moles conversion ratio 49.43%.Rectification under vacuum,
Obtain 72.3 grams of faint yellow solid, 83.8 DEG C of fusing point, p-aminophenyl nitrile content 98.8%.
Claims (8)
1. a kind of synthetic method of p-aminophenyl formonitrile HCN, it is characterized in that：With to halogenated trihalomethyl group benzene or to trihalomethyl group
Aniline is starting material or intermediate, and in alcohol and water mixture is molten, adduction enters aminating agent, by catalyst, co-catalyst 100
~250 DEG C, catalytic reaction under 1.0~10.0MPa, reaction product is through the isolated p-aminophenyl formonitrile HCN of rectifying.
2. the synthetic method of p-aminophenyl formonitrile HCN according to claim 1, it is characterized in that：After catalytic reaction, cooling
To less than 50 DEG C, release, when release, starts gas boosting pump, and excess of ammonia is compressed, is condensed into liquefied ammonia for feeding intake；Let out release
To normal pressure, material being transferred to normal-pressure reaction kettle removing solvent, catalyst residue is then demultiplex out, liquid material rectifying separates,
Obtain p-aminophenyl formonitrile HCN.
3. the synthetic method of p-aminophenyl formonitrile HCN according to claim 1 or 2, it is characterized in that：It is described to halogenated three halogen
For methylbenzene, general formula isR is any one of fluorine, chlorine, bromine, iodine or amido in formula, and X, Y, Z are
Any one of fluorine, chlorine, bromine, iodine or amido or arbitrary different combination.
4. the synthetic method of p-aminophenyl formonitrile HCN according to claim 1 or 2, it is characterized in that：The catalyst is cuprous
The combination of salt or cuprous salt and co-catalyst.
5. the synthetic method of p-aminophenyl formonitrile HCN according to claim 4, it is characterized in that：The cuprous salt is protochloride
The combination of one or more of copper, cuprous cyanide, copper fluoride, cuprous bromide, cuprous iodide, cuprous sulfate；Co-catalyst
For the combination of potassium fluoride or highly basic or highly basic and potassium fluoride.
6. the synthetic method of p-aminophenyl formonitrile HCN according to claim 5, it is characterized in that：Highly basic is described in co-catalyst
Inorganic base.
7. the synthetic method of p-aminophenyl formonitrile HCN according to claim 1 or 2, it is characterized in that：The alcohol is methanol or second
Alcohol.
8. the synthetic method of p-aminophenyl formonitrile HCN according to claim 1 or 2, it is characterized in that：The aminating agent is ammonium hydroxide
Or ammonia；Molar ratio to halogenated trihalomethyl group benzene and aminating agent is 1:3~1:20.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711390502.XA CN108059605A (en) | 2017-12-21 | 2017-12-21 | The synthetic method of p-aminophenyl formonitrile HCN |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711390502.XA CN108059605A (en) | 2017-12-21 | 2017-12-21 | The synthetic method of p-aminophenyl formonitrile HCN |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108059605A true CN108059605A (en) | 2018-05-22 |
Family
ID=62139489
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711390502.XA Pending CN108059605A (en) | 2017-12-21 | 2017-12-21 | The synthetic method of p-aminophenyl formonitrile HCN |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108059605A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111269144A (en) * | 2020-04-07 | 2020-06-12 | 新乡市锦源化工有限公司 | Preparation method of aminobenzonitrile |
| CN113967449A (en) * | 2021-10-16 | 2022-01-25 | 江苏优普生物化学科技股份有限公司 | Chemical colloid production is with catalytic reaction equipment that has quantitative material loading structure |
-
2017
- 2017-12-21 CN CN201711390502.XA patent/CN108059605A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| JUNMIN CHEN ET AL.: "Simple and efficient CuI/PEG-400 system for amination of aryl halides with aqueous ammonia", 《TETRAHEDRON LETTERS》 * |
| NING XIA ET AL.: "A Very Simple Copper-Catalyzed Synthesis of Anilines by Employing Aqueous Ammonia", 《ANGEW. CHEM. INT. ED.》 * |
| TAMARA A. VAGANOVA ET AL.: "Selective one-pot synthesis of aminopolyhalobenzonitriles from polyhalobenzotrichlorides in anhydrous ammonia", 《JOURNAL OF FLUORINE CHEMISTRY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111269144A (en) * | 2020-04-07 | 2020-06-12 | 新乡市锦源化工有限公司 | Preparation method of aminobenzonitrile |
| CN113967449A (en) * | 2021-10-16 | 2022-01-25 | 江苏优普生物化学科技股份有限公司 | Chemical colloid production is with catalytic reaction equipment that has quantitative material loading structure |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110498730B (en) | Synthetic method of 1,2, 4-trifluorobenzene | |
| CN106905104B (en) | Synthesis method of 2-bromo-5-fluorobenzotrifluoride | |
| CN103044223B (en) | Method for continuously preparing pseudo ionone of vitamin A intermediate | |
| CN111662185A (en) | Synthesis method of N-methyl o-fluoroaniline | |
| CN108059605A (en) | The synthetic method of p-aminophenyl formonitrile HCN | |
| CN103467239A (en) | Technique for preparing monochlorodifluoromethane by decomposing trifluoromethane | |
| CN102336689A (en) | Preparation and refining method of 4-Cl-(trifluoromethyl) benzene sulfonyl chloride | |
| CN103086895B (en) | Method for preparing aromatic amine from mixed nitrochlorobenzene | |
| CN103420842B (en) | Preparation method for 2,3,4-trifluoronitrobenzene | |
| CN107739294B (en) | Method for preparing hydrofluorocyclopentene by gas phase dehydrofluorination | |
| CN112300009A (en) | Preparation method of m-phenylenediamine | |
| CN109809959A (en) | A kind of preparation method of 1,1,1,2,3- pentachloropropane | |
| CN101698664B (en) | Preparation method of pharmaceutical intermediate 2-amine methylpyrazine hydrochloride | |
| CN114516780B (en) | Preparation method of 3,4, 5-trifluoro-bromobenzene | |
| CN108299259B (en) | Preparation method of 2-amino-5-thiophenyl- (2-methoxy) acetanilide | |
| WO2017211129A1 (en) | Method for manufacturing ephedrine or pseudoephedrine and ephedrine or pseudoephedrine intermediate | |
| CN105348130A (en) | Preparation method of N,N-dimethyl propyl acrylamide | |
| CN103319335B (en) | Preparation method of D-(-)-O-methyl mandelic acid chloride | |
| CN106478422B (en) | A kind of preparation method of paranitrophenylacetic acid | |
| CN102924362A (en) | Preparation method of hexahydro-2-cyclopentyl-pyrryl amine hydrochloride | |
| CN102718649B (en) | Chemical synthesis method of 2, 3, 4, 5-tetrafluoro-benzoic acid | |
| CN1258519C (en) | Method for coproducing 3-chloro-4-fluoroaniline and 2,6-dichlorofluobenzene | |
| CN114436952A (en) | Synthesis method of 2-methoxy-3-amino-5-pyridine boronic acid pinacol ester and intermediate thereof | |
| CN111004184A (en) | Synthesis process of 4, 6-dichloropyrimidine | |
| CN103102276A (en) | Method for preparing 3,5-dichloroaniline |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180522 |