CN101265229A - Method for preparing 2-substituted-6-trifluoromethylnicotinonitrile or acid thereof - Google Patents
Method for preparing 2-substituted-6-trifluoromethylnicotinonitrile or acid thereof Download PDFInfo
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- CN101265229A CN101265229A CNA2008100369379A CN200810036937A CN101265229A CN 101265229 A CN101265229 A CN 101265229A CN A2008100369379 A CNA2008100369379 A CN A2008100369379A CN 200810036937 A CN200810036937 A CN 200810036937A CN 101265229 A CN101265229 A CN 101265229A
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- Prior art keywords
- trifluoromethyl
- cigarette nitrile
- acid
- trifluoromethyl cigarette
- replacement
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- 239000002253 acid Substances 0.000 title claims abstract description 24
- -1 2-substituted-6-trifluoromethylnicotinonitrile Chemical class 0.000 title claims abstract description 8
- 238000000034 method Methods 0.000 title abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 239000002994 raw material Substances 0.000 claims abstract description 17
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
- 150000002825 nitriles Chemical class 0.000 claims description 68
- 235000019504 cigarettes Nutrition 0.000 claims description 67
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 239000003513 alkali Substances 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- JPOIZUVDMRHIIT-UHFFFAOYSA-N 2-oxo-6-(trifluoromethyl)-1h-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)NC1=O JPOIZUVDMRHIIT-UHFFFAOYSA-N 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 4
- 229910017604 nitric acid Inorganic materials 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 150000003053 piperidines Chemical class 0.000 claims description 3
- 150000003233 pyrroles Chemical class 0.000 claims description 3
- 150000003335 secondary amines Chemical class 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 abstract 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 abstract 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 238000000605 extraction Methods 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 238000001035 drying Methods 0.000 description 6
- 238000000967 suction filtration Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000012450 pharmaceutical intermediate Substances 0.000 description 4
- DXRBTBMFFGEVCX-UHFFFAOYSA-N 2-chloro-6-(trifluoromethyl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)N=C1Cl DXRBTBMFFGEVCX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- JNYLMODTPLSLIF-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)N=C1 JNYLMODTPLSLIF-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
Abstract
The invention relates to a method of preparing 2-substituted-6-trifluoromethyl nicotinonitrile or acid thereof. 2-oxhydryl-6-trifluoromethyl nicotinonitrile is used as raw material for preparation so as to manufacture the 2-substituted-6-trifluoromethyl nicotinonitrile or the acid; a reaction formula is represented in the above formula; in the formula, X is -CH or -COOH, and Y is -Cl or -NR1R2, wherein, R1 or R2 is one of hydrogen groups, C1-C10 alkyl, C1-C10 alkoxyl, phenyl, substituted phenyl, azide groups, drewamine, piperidine, pyrrole, vermex, azetidine-3-alcohol, and 1-benzhydryl-azetidine-3-primary amine. The method has the advantages of high product yield rate, simple operation, and being suitable for the industrial production.
Description
Technical field
The present invention relates to 2-replacement-6-trifluoromethyl cigarette nitrile or its sour preparation method, this compounds is mainly used in fields such as medicine, food, feed, can also make the intermediate of sterilant etc.
Background technology
2-chloro-6-trifluoromethyl cigarette nitrile, 2-hydroxyl-6-trifluoromethyl nicotinic acid are important pharmaceutical intermediate, but also do not report its synthetic method so far.
2-substituted amido-6-trifluoromethyl cigarette nitrile is important pharmaceutical intermediate; once reported a kind of preparation method in the document; with trifluoroacetyl group ethyl vinyl ether and 3-amido-3-pyrroles's (morpholine)-1-third rare nitrile is raw material; acetonitrile was made the solvent reacting by heating 2 hours, obtained 2-pyrroles's (morpholine)-6-trifluoromethyl cigarette nitrile.
(Journal；Cocco，Maria?Teresa；Congiu，Cenzo；Onnis，Valentina；JHTCAD；J.Heterocycl.Chem.；EN；32；2；1995；543-546.)
The document synthetic route:
Wherein, R is O or CH
2
2-substituted amido-6-trifluoromethyl nicotinic acid is important psychological treatment intermediate, reports once in the document that a kind of preparation method is raw material and pyrroles's (morpholine) reaction with 2-chloro-6-trifluoromethyl nicotinic acid, obtained 2-substituted amido-6-trifluoromethyl nicotinic acid.(Elizabeth?M.Doherty，*，
Christopher?Fotsch，
Yunxin?Bo，
Partha?P.Chakrabarti，
NingChen，
Narender?Gavva，
Nianhe?Han，
Michael?G.Kelly，JohnKincaid，Lana?Klionsky，
Qingyian?Liu，
Vassil?I.Ognyanov，
Rami?Tamir，
Xianghong?Wang，
Jiawang?Zhu，
Mark?H.Norman，
andJames?J.S.Treanor
J.Med.Chem.En；48；1；2005；71-90)。
The document synthetic route:
Wherein, R is O or CH
2
Prepare 2-substituted amido-6-trifluoromethyl nicotinic acid from 2-chloro-6-trifluoromethyl nicotinic acid, its reaction yield is not very stable, therefore applicant of the present invention considers from another route, prepare 2-substituted amido-6-trifluoromethyl cigarette nitrile from 2-chloro-6-trifluoromethyl cigarette nitrile, its reacting phase is when easy, and hydrolysis almost can obtain quantitative 2-chloro-6-trifluoromethyl nicotinic acid again.
Summary of the invention:
The purpose of this invention is to provide a kind of product yield height, simple to operate and to be suitable for industrial be raw material with 2-hydroxyl-6-trifluoromethyl cigarette nitrile, prepare 2-replacement-6-trifluoromethyl cigarette nitrile or its sour method, series product comprise 2-chloro-6-trifluoromethyl cigarette nitrile, 2-hydroxyl-6-trifluoromethyl nicotinic acid, 2-substituted amido-6-trifluoromethyl cigarette nitrile, 2-substituted amido-pharmaceutical intermediates such as 6-trifluoromethyl nicotinic acid.
The present invention solves the problems of the technologies described above the technical scheme of being taked:
A kind of 2-replacement-6-trifluoromethyl cigarette nitrile or its sour preparation method are raw material with 2-hydroxyl-6-trifluoromethyl cigarette nitrile, make 2-replacement-6-trifluoromethyl cigarette nitrile or its acid, and reaction formula is as follows:
In the formula, X is-CN or-COOH; Y is-Cl or-NR
1R
2, wherein, R
1Or R
2Be hydrogen base, C
1～C
10Alkyl, C
1～C
10Alkoxyl group, phenyl, substituted-phenyl, azido-, a kind of in morpholine, piperidines, pyrroles, piperazine, aza-cyclobutane-3-alcohol, the 1-diphenyl-methyl-azetidine-3-primary amine.
Described R
1, R
2For identical or different.
On the basis of such scheme, provide the preparation method of 2-chloro-6-trifluoromethyl cigarette nitrile: with 2-hydroxyl-6-trifluoromethyl cigarette nitrile is that raw material and phosphorus pentachloride and phosphorus oxychloride are blended in 80～110 ℃ of reactions down, handle through routine, be specially: follow the tracks of with HPLC, to reacting completely, cooling, add in the frozen water, use dichloromethane extraction, the organic phase drying, suction filtration, be spin-dried for, obtain product 2-chloro-6-trifluoromethyl cigarette nitrile, reaction formula is expressed as follows:
The reaction mol ratio of described phosphorus pentachloride and 2-hydroxyl-6-trifluoromethyl cigarette nitrile is 1～3: 1; The reaction mol ratio of phosphorus oxychloride and 2-hydroxyl-6-trifluoromethyl cigarette nitrile is 1～6: 1.
Concrete, the reaction mol ratio of phosphorus pentachloride and 2-hydroxyl-6-trifluoromethyl cigarette nitrile can be 1,1.2,1.4,1.6,1.8,2,2.2,2.4,2.6,2.8, and a kind of in 3: 1;
The reaction mol ratio of phosphorus oxychloride and 2-hydroxyl-6-trifluoromethyl cigarette nitrile can be 1,1.2,1.4,1.6,1.8,2,2.2,2.4,2.6,2.8,3,3.2,3.4,3.6,3.8,4,4.2,4.4,4.6,4.8,5,5.2,5.6,5.8, and a kind of in 6: 1.
On the basis of such scheme, the preparation method of 2-hydroxyl-6-trifluoromethyl nicotinic acid is provided, be raw material with 2-chloro-6-trifluoromethyl cigarette nitrile, be blended in 80～150 ℃ of reactions down with acid or alkali, handle through routine, be specially: follow the tracks of with HPLC, to reacting completely, cooling, add frozen water, use ethyl acetate extraction, be spin-dried for, obtain product 2-hydroxyl-6-trifluoromethyl nicotinic acid, reaction formula is expressed as follows:
Wherein, described acid is a kind of in hydrochloric acid, sulfuric acid, the nitric acid, and the mass concentration of acid is 20～50%, and acid is 0.5～5: 1 with the mol ratio of 2-chloro-6-trifluoromethyl cigarette nitrile; Described alkali is sodium hydroxide or potassium hydroxide, and the mass concentration of alkali is 20～40%, and the mol ratio of alkali and 2-chloro-6-trifluoromethyl cigarette nitrile is 0.5～5: 1.
Concrete, acid can be 0.5,0.8,1,1.2,1.5,1.8,2,2.2,2.5,3,3.3,3.5,3.8,4,4.2,4.5,4.8,5: 1 with the reaction mol ratio of 2-chloro-6-trifluoromethyl cigarette nitrile.
The reaction mol ratio of alkali and 2-chloro-6-trifluoromethyl cigarette nitrile can be 0.5,0.8,1,1.2,1.5,1.8,2,2.2,2.5,3,3.3,3.5,3.8,4,4.2,4.5,4.8,5: 1.
On the basis of such scheme, the preparation method of 2-substituted amido-6-trifluoromethyl cigarette nitrile is provided, be raw material and secondary amine HNR with 2-chloro-6-trifluoromethyl cigarette nitrile
1R
220～150 ℃ of reactions are down handled through routine in solvent, are specially: follow the tracks of with HPLC, to reacting completely, handle, add water, with methyl tertiary butyl ether (MTBE) extraction 3 times, drying, suction filtration is spin-dried for, and obtains product 2-substituted amido-6-trifluoromethyl cigarette nitrile, is expressed as follows with reaction formula:
The reaction mol ratio of described secondary amine and 2-chloro-6-trifluoromethyl cigarette nitrile is 1～3: 1, and described solvent is a kind of or its combination in ethanol, methylene dichloride, ethyl acetate, dimethyl formamide, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), benzene, the toluene.
Concrete, the reaction mol ratio of secondary amine and 2-chloro-6-trifluoromethyl cigarette nitrile can be 1,1.2,1.4,1.6,1.8,2,2.2,2.4,2.6,2.8, and 3: 1.
On the basis of such scheme, the preparation method of 2-substituted-amino-6-trifluoromethyl nicotinic acid is provided, with 2-substituted amido-6-trifluoromethyl cigarette nitrile is that raw material and diluted acid mix 50～100 ℃ of reactions down, handle through routine, be specially: follow the tracks of with HPLC,, handle to reacting completely, add water, regulate pH to alkalescence with sodium hydroxide, use dichloromethane extraction, water is regulated pH to acid with dilute hydrochloric acid, use dichloromethane extraction, the organic phase drying, suction filtration is spin-dried for, obtain product 2-substituted amido-6-trifluoromethyl nicotinic acid, be expressed as follows with reaction formula:
Described diluted acid is a kind of in hydrochloric acid, sulfuric acid, the nitric acid, and the mass concentration of acid is 20～35%, and the mol ratio of diluted acid and 2-substituted amido-6-trifluoromethyl cigarette nitrile is 2～6: 1.
Concrete, the mol ratio of diluted acid and 2-substituted amido-6-trifluoromethyl cigarette nitrile can be 2,2.5,3,3.5,4,4.5,5,5.5,6: 1.
The invention has the beneficial effects as follows: the present invention is a raw material with 2-hydroxyl-6-trifluoromethyl cigarette nitrile, prepare multiple 2-replacement-6-trifluoromethyl cigarette nitrile or its sour series product, comprise 2-chloro-6-trifluoromethyl cigarette nitrile, 2-hydroxyl-6-trifluoromethyl nicotinic acid, 2-substituted amido-6-trifluoromethyl cigarette nitrile, 2-substituted amido-pharmaceutical intermediates such as 6-trifluoromethyl nicotinic acid, the product yield height, the industrial production that is suitable for simple to operate can directly reach the purpose that reduces cost.
Embodiment
Embodiment 1
In the three-necked bottle of 250ml, add 2-hydroxyl-6-trifluoromethyl cigarette nitrile, 16.2g phosphorus pentachloride and the 40g phosphorus oxychloride of 10g, be heated to 100 ℃, follow the tracks of with HPLC, reacted 6 hours, raw material reaction is intact, and cooling adds in the frozen water, use dichloromethane extraction, organic phase drying, suction filtration, be spin-dried for, obtain 9.2g solid 2-chloro-6-trifluoromethyl cigarette nitrile, purity is 93%.MS(EI)M
+206(80.61)(M+2)
+208(25.32)。
Embodiment 2
In single neck bottle of 50ml, 2-chloro-6-trifluoromethyl cigarette nitrile 1g that adding embodiment 1 makes and the sulfuric acid of 1.9g 40%, magnetic agitation, 100 ℃ of oil bath heating, follow the tracks of with HPLC, reacted 4 days, raw material reaction is intact, cooling, add frozen water, use ethyl acetate extraction, be spin-dried for, obtain 0.88g yellow solid 2-hydroxyl-6-trifluoromethyl nicotinic acid, purity is 95.6%.MS(EI)M
+207(37.64)。
Embodiment 3
In single neck bottle of 50ml, 2-chloro-6-trifluoromethyl cigarette nitrile 1g that makes among the adding embodiment 1 and the piperidines of 0.6g, 5g ethanol, magnetic agitation, normal-temperature reaction 22 hours, HPLC follows the tracks of reaction and finishes, and handles, add water, with MTBE extraction 3 times, drying, suction filtration, be spin-dried for and obtain 0.98g solid 2-piperidines-6-trifluoromethyl cigarette nitrile, wherein, purity is: 96.8%
1HNMR (CDCl
3) δ 1.71 (s, 6H), δ 3.78 (s, 4H), δ 6.95 (d, J=7.8Hz, 1H), δ 7.87 (d, J=7.8Hz, 1H) MS (EI) M
+255 (74.8).
Embodiment 4
In single neck bottle of 50ml, 2-piperidines-6-trifluoromethyl cigarette nitrile 1.7g that makes among the adding embodiment 3 and the sulfuric acid of 3.8g 40%, magnetic agitation, heat 100 ℃, reacted 24 hours, track to reaction with HPLC and finish, handle, add water, regulate pH to alkalescence, use dichloromethane extraction with sodium hydroxide, water is regulated pH to acid with dilute hydrochloric acid, use dichloromethane extraction, organic phase drying, suction filtration, be spin-dried for and obtain 1.3g liquid 2-piperidines-6-trifluoromethyl nicotinic acid, purity is: 98.7%.
1HNMR(CDCl
3)δ1.71(s，6H)，δ3.78(s，4H)，δ6.95(d，J＝7.8Hz，1H)，δ7.87(d，J＝7.8Hz，1H)MS(EI)M
+274(31.24)。
Claims (10)
1, a kind of 2-replacement-6-trifluoromethyl cigarette nitrile or its sour preparation method are raw material with 2-hydroxyl-6-trifluoromethyl cigarette nitrile, and reaction formula is as follows:
In the formula, X is-CN or-COOH; Y is-Cl or-NR
1R
2, wherein, R
1Or R
2Be hydrogen base, C
1～C
10Alkyl, C
1～C
10Alkoxyl group, phenyl, substituted-phenyl, azido-, a kind of in morpholine, piperidines, pyrroles, piperazine, aza-cyclobutane-3-alcohol, the 1-diphenyl-methyl-azetidine-3-primary amine.
2,2-replacement-6-trifluoromethyl cigarette nitrile according to claim 1 or its sour preparation method, it is characterized in that: described R1, R2 are identical or different.
3,2-replacement-6-trifluoromethyl cigarette nitrile according to claim 1 or its sour preparation method, it is characterized in that: with 2-hydroxyl-6-trifluoromethyl cigarette nitrile is raw material, be blended in 80～110 ℃ of reactions down with phosphorus pentachloride and phosphorus oxychloride, obtain 2-chloro-6-trifluoromethyl cigarette nitrile, reaction formula is expressed as follows:
4,2-replacement-6-trifluoromethyl cigarette nitrile according to claim 3 or its sour preparation method is characterized in that: the mol ratio of described phosphorus pentachloride and 2-hydroxyl-6-trifluoromethyl cigarette nitrile is 1～3: 1; The mol ratio of phosphorus oxychloride and 2-hydroxyl-6-trifluoromethyl cigarette nitrile is 1～6: 1.
5, according to claim 3 or 4 described 2-replacement-6-trifluoromethyl cigarette nitrile or its sour preparation methods, it is characterized in that: with 2-chloro-6-trifluoromethyl cigarette nitrile is that raw material and acid or alkali are blended in 80～150 ℃ of reactions down, obtain 2-hydroxyl-6-trifluoromethyl nicotinic acid, reaction formula is expressed as follows:
6,2-replacement-6-trifluoromethyl cigarette nitrile according to claim 5 or its sour preparation method, it is characterized in that: described acid is a kind of in hydrochloric acid, sulfuric acid, the nitric acid, the concentration of acid is 20～50%, and acid is 0.5～5: 1 with the mol ratio of 2-chloro-6-trifluoromethyl cigarette nitrile; Described alkali is sodium hydroxide or potassium hydroxide, and the concentration of alkali is 20～40%, and the mol ratio of alkali and 2-chloro-6-trifluoromethyl cigarette nitrile is 0.5～5: 1.
7, according to claim 3 or 4 described 2-replacement-6-trifluoromethyl cigarette nitrile or its sour preparation methods, it is characterized in that: with 2-chloro-6-trifluoromethyl cigarette nitrile is raw material and secondary amine HNR
1R
220～150 ℃ of reactions down obtain 2-substituted amido-6-trifluoromethyl cigarette nitrile in solvent, are expressed as follows with reaction formula:
8,2-replacement-6-trifluoromethyl cigarette nitrile according to claim 7 or its sour preparation method, it is characterized in that: the mol ratio of described secondary amine and 2-chloro-6-trifluoromethyl cigarette nitrile is 1～3: 1, and described solvent is a kind of in ethanol, methylene dichloride, ethyl acetate, dimethyl formamide, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), benzene, the toluene.
9, according to claim 7 or 8 described 2-replacement-6-trifluoromethyl cigarette nitrile or its sour preparation methods, it is characterized in that: with 2-substituted amido-6-trifluoromethyl cigarette nitrile is that raw material and diluted acid mix 50～100 ℃ of reactions down, obtain 2-substituted amido-6-trifluoromethyl nicotinic acid, be expressed as follows with reaction formula:
10,2-replacement-6-trifluoromethyl cigarette nitrile according to claim 9 or its sour preparation method, it is characterized in that: described diluted acid is a kind of in hydrochloric acid, sulfuric acid, the nitric acid, the concentration of diluted acid is 20～35%, and the mol ratio of diluted acid and 2-substituted amido-6-trifluoromethyl cigarette nitrile is 2～6: 1.
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|---|---|---|---|
| CNA2008100369379A CN101265229A (en) | 2008-04-30 | 2008-04-30 | Method for preparing 2-substituted-6-trifluoromethylnicotinonitrile or acid thereof |
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|---|---|---|---|
| CNA2008100369379A CN101265229A (en) | 2008-04-30 | 2008-04-30 | Method for preparing 2-substituted-6-trifluoromethylnicotinonitrile or acid thereof |
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|---|---|
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ID=39987946
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103539747A (en) * | 2013-09-24 | 2014-01-29 | 重庆紫光化工股份有限公司 | Preparation method of 4,6-dichloropyrimidine |
-
2008
- 2008-04-30 CN CNA2008100369379A patent/CN101265229A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103539747A (en) * | 2013-09-24 | 2014-01-29 | 重庆紫光化工股份有限公司 | Preparation method of 4,6-dichloropyrimidine |
| CN103539747B (en) * | 2013-09-24 | 2016-08-10 | 重庆紫光化工股份有限公司 | The preparation method of 4,6-dichloro pyrimidine |
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