CN106431979B - 一种2-硝基-4-三氟甲基苯腈的制备方法 - Google Patents
一种2-硝基-4-三氟甲基苯腈的制备方法 Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 38
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- 239000003054 catalyst Substances 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 12
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000007864 aqueous solution Substances 0.000 claims abstract description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims abstract description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical class CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000012043 crude product Substances 0.000 claims abstract description 3
- 239000012065 filter cake Substances 0.000 claims abstract description 3
- 238000001914 filtration Methods 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims abstract description 3
- 238000009413 insulation Methods 0.000 claims abstract 2
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- -1 nitrogenous organic base Chemical class 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 150000004820 halides Chemical class 0.000 claims description 6
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 6
- BQCWLXXZTCLGSZ-UHFFFAOYSA-N 2-nitro-4-(trifluoromethyl)benzonitrile Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1C#N BQCWLXXZTCLGSZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 4
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical group [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 3
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical group CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000011775 sodium fluoride Substances 0.000 claims description 2
- 235000013024 sodium fluoride Nutrition 0.000 claims description 2
- 235000009518 sodium iodide Nutrition 0.000 claims description 2
- 238000010792 warming Methods 0.000 claims description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims 4
- 229910052802 copper Inorganic materials 0.000 claims 2
- 239000010949 copper Substances 0.000 claims 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 claims 1
- 238000003810 ethyl acetate extraction Methods 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims 1
- JLKDVMWYMMLWTI-UHFFFAOYSA-M potassium iodate Chemical group [K+].[O-]I(=O)=O JLKDVMWYMMLWTI-UHFFFAOYSA-M 0.000 claims 1
- 239000000376 reactant Substances 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 5
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 abstract description 4
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 238000000605 extraction Methods 0.000 abstract description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 2
- DRNJIKRLQJRKMM-UHFFFAOYSA-N 4-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC=C(C#N)C=C1 DRNJIKRLQJRKMM-UHFFFAOYSA-N 0.000 abstract 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 6
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000002363 herbicidal effect Effects 0.000 description 4
- 239000004009 herbicide Substances 0.000 description 4
- TZGFQIXRVUHDLE-UHFFFAOYSA-N 1-chloro-2-nitro-4-(trifluoromethyl)benzene Chemical class [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1Cl TZGFQIXRVUHDLE-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 2
- RUHKUUFAKLLDEY-UHFFFAOYSA-N FC(C1=CC=CC=C1)(F)F.[Br] Chemical class FC(C1=CC=CC=C1)(F)F.[Br] RUHKUUFAKLLDEY-UHFFFAOYSA-N 0.000 description 2
- DXRFZHILMCWCNG-UHFFFAOYSA-N N,N-dimethyl-1,8-naphthyridin-2-amine Chemical compound C1=CC=NC2=NC(N(C)C)=CC=C21 DXRFZHILMCWCNG-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical class CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 1
- DDNRGAUZMIFKQS-UHFFFAOYSA-N 4-chloro-2-nitro-1-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1C(F)(F)F DDNRGAUZMIFKQS-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 241001269238 Data Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- IPLJNQFXJUCRNH-UHFFFAOYSA-L nickel(2+);dibromide Chemical compound [Ni+2].[Br-].[Br-] IPLJNQFXJUCRNH-UHFFFAOYSA-L 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- UWNWYIUODRPXKH-UHFFFAOYSA-N toluene;hydrofluoride Chemical compound F.CC1=CC=CC=C1 UWNWYIUODRPXKH-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/14—Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/08—Halides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/08—Halides
- B01J27/10—Chlorides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0237—Amines
- B01J31/0238—Amines with a primary amino group
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0244—Nitrogen containing compounds with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/26—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/19—Catalysts containing parts with different compositions
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
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Abstract
本发明公开了一种2‑硝基‑4‑三氟甲基苯腈的制备方法，其包括将氰化亚铜溶解到N‑甲基吡咯烷酮中，再加入催化剂，加完后在150‑160℃保温反应8‑14h，GC检测至2‑硝基‑4‑三氟甲基卤代苯反应完毕；降至室温，在搅拌下把溶液倒入2‑硝基‑4‑三氟甲基苯腈粗品摩尔量4.0‑8.0倍浓度为40‑50%乙酸乙酯水溶液中，过滤去除铜盐，滤饼用2‑硝基‑4‑三氟甲基苯腈的摩尔量2‑4倍的乙酸乙酯洗涤萃取，合并油层，再用水洗涤油层，最后用无水硫酸镁干燥后真空精馏，得到2‑硝基‑4‑三氟甲基苯腈精品。本发明避免使用剧毒氰化试剂氰化钠、氰化钾，采用催化剂，提高了反应选择性与收率，工艺温和，收率90‑93%。
Description
技术领域
本发明涉及一种苯腈类化合物的制备方法，特别涉及一种2-硝基-4-三氟甲基苯腈的制备方法。
背景技术
2-硝基-4-三氟甲基苯腈（NCB）是一种特殊芳香族氟化合物，是医药、农药等多种化合物的中间体。在医药方面，是合成治疗血糖过低、止痛、降血压等药物的中间体；在农药方面，属高效、低毒、低用量农药中间体。NCB还可用于制备烯醇衍生物用作除草剂，对具有抗药性的杂草防治效果特别有效；在吡啶环中引入三氟甲基合成的除草剂，为激素型选择性芽后除草剂，专门用于防治阔叶型杂草，是当前除草剂领域开发研究主要方向。
EP1000929描述了使用3-硝基-4-氟三氟甲苯和氰化钠或氰化钾作原料合成2-硝基-4-三氟甲基苯腈的方法，该方法包括3-硝基-4-氟三氟甲苯和氰化钠或者氰化钾分别在乙腈、氰苯、THF等溶剂中反应得到2-硝基-4-三氟甲基苯腈，反应最高收率47%。US4886936、US6635780等文献描述了使用3-硝基-4-溴三氟甲苯和氰化亚铜作原料合成2-硝基-4-三氟甲基苯腈时，反应选择性和转化率非常好；但是3-硝基-4-溴三氟甲苯市场供应稀少，并且价格昂贵。而采用3-硝基-4-氯三氟甲苯和氰化亚铜作原料合成2-硝基-4-三氟甲基苯腈时，反应选择性差，产率较低。
根据CN101585783A，使用溴化镍催化剂，氰化亚铜做氰化剂，采用3-硝基-4-氯三氟甲苯做反应原料，反应选择性和转化率都得到比较理想的效果。但是溴化镍价格较为昂贵，不宜大量使用。
CN102675151A，使用氯化亚铜和/或溴化亚铜做催化剂，采用3-硝基-4-氯三氟甲苯与亚铁氰化钾反应制备产物，但反应时间长，产率较低，
此外，这些方法都使用了高毒的氰化试剂作为氰化剂，比如：氰化钾和氰化钠等，或者它们的混合试剂，并且其中因氰化亚铜效果理想而优选。
发明内容
针对上述技术缺陷，本发明提供了一种2-硝基-4-三氟甲基苯腈的合成方法，使得合成反应的条件温和、所使用的大多数原料毒性较低、生产成本低且利于工业化生产。
本发明的技术方案为，一种2-硝基-4-三氟甲基苯腈的合成方法，其步骤如下：
将氰化亚铜溶解到溶剂中，搅拌全溶后升温到150℃-160℃，用分水器脱去水分，然后降温到110~120℃；加入催化剂与2-硝基-4-三氟甲基卤代苯，加完后在150-160℃保温反应8-14h；GC检测至2-硝基-4-三氟甲基卤代苯反应完毕。降至室温，在搅拌下把溶液倒入2-硝基-4-三氟甲基苯腈粗品摩尔量4.0-8.0倍浓度为40-50%乙酸乙酯水溶液中，过滤去除铜盐，滤饼用2-硝基-4-三氟甲基苯腈的摩尔量2-4倍的乙酸乙酯洗涤萃取，合并油层，再用水洗涤油层，最后用无水硫酸镁干燥后真空精馏，得到2-硝基-4-三氟甲基苯腈。
2-硝基-4-三氟甲基卤代苯的结构式如下：
；
2-硝基-4-三氟甲基苯腈结构式如下：
。
氰化亚铜与2-硝基-4-三氟甲基卤代苯的摩尔比为（0.5~3.0）: 1，催化剂与2-硝基-4-三氟甲基卤代苯摩尔比为（0.05-1）：1；
所述溶剂包括N,N二甲基甲酰胺，N,N-二甲基乙酰胺、二甲基亚砜、N-甲基吡咯烷酮、环丁砜、苯腈中的一种或多种；
所述催化剂为含氮有机碱与卤化物制备的催化剂，有机碱与卤化物的总量摩尔比为1:（0.1-3）。催化剂中含氮有机碱包括乙胺、二乙胺、三乙胺、丙胺、吡啶、3-甲基吡啶、4-二甲氨基吡啶等有机碱中一种；卤化物包括氟化钠、氯化钠、溴化钠、碘化钠、氟化钾、氯化钾、溴化钾、碘化钾中一种。
本发明提供的邻硝基苯腈类化合物制备方法的有益效果如下：
（1）采用自制的组合催化剂，产品选择性和收率较高。
（2）所用原材料除氰化亚铜有一定毒性以外，其他原料毒性相对较低，有利于生产操作者的身体健康。
（3）工艺简单，反应条件温和。
具体实施方式
下面结合实施例对本发明作进一步的说明。
实施例1
在干燥氮气保护下，向反应瓶中加入N-甲基吡咯烷酮90.2g，氰化亚铜13.4g，升温回流分水，降温至110℃，加入2-硝基-4-氯三氟甲苯22.5g，催化剂1.1g（二甲氨基吡啶0.7g，碘化钾0.4g）。开启搅拌，加热至150-160℃，搅拌反应12h。随后，在氮气保护下降温至室温，取样GC分析，原料反应完毕。加入60.0g乙酸乙酯和20.0g水，搅拌，分出有机相，水相用20.0g乙酸乙酯萃取，合并有机相，经无水硫酸钠干燥，真空精馏得产品19.8g，收率91.5%，LC含量98.1%。2-硝基-4-三氟甲基苯腈质谱数据（EI）所示：216（M+），170（M-NO2）。
实施例2
在干燥氮气保护下，向反应瓶中加入DMF 88.7g，氰化亚铜11.2g，升温回流分水，分水完毕后，降温至105℃，加入3-硝基-4-氯三氟甲苯22.5g，催化剂1.3g（吡啶0.8，氯化钾0.5g）。开启搅拌，加热至150-160℃，搅拌反应12h。随后，在氮气保护下降温至室温，取样GC分析，原料反应完毕。加入60.0g乙酸乙酯和20.0g水，搅拌，分出有机相，水相用20.0g乙酸乙酯萃取，合并有机相，经无水硫酸钠干燥，真空精馏得产品19.1g，收率88.4%，LC含量97.2%。
实施例3
在干燥氮气保护下，向反应瓶中加入环丁砜 95.6g，氰化亚铜14.6g，升温回流分水，分水完毕后，降温至110℃，加入3-硝基-4-氯三氟甲苯22.5g，，催化剂0.3g（二异丙基乙基胺0.2g，溴化钾0.1g）。开启搅拌，加热至150-160℃，搅拌反应12h。随后，在氮气保护下降温至室温，取样GC分析，原料反应完毕。加入60.0g乙酸乙酯和20.0g水，搅拌，分出有机相，水相用20.0g乙酸乙酯萃取，合并有机相，经无水硫酸钠干燥，真空精馏得产品18.4g，收率85.3%，LC含量95.7%。
Claims (8)
1.一种2-硝基-4-三氟甲基苯腈的制备方法， 其特征在于，包括以下步骤：将氰化亚铜溶解到溶剂中，搅拌全溶后升温到150℃-160℃，用分水器脱去水分，然后降温到110~120℃；加入催化剂与2-硝基-4-三氟甲基卤代苯，加完后在150-160℃保温反应8-14h；GC检测至2-硝基-4-三氟甲基卤代苯反应完毕，后经精制而得2-硝基-4-三氟甲基苯腈；所述催化剂为含氮有机碱与卤化物制备的催化剂，所述卤化物为氟化钠、氯化钠、溴化钠、碘化钠、氟化钾、氯化钾、溴化钾和碘化钾中的一种，所述含氮有机碱为乙胺、二乙胺、三乙胺、丙胺、3-甲基吡啶和4-二甲氨基吡啶中的一种。
2.根据权利要求1所述的制备方法，其特征在于：2-硝基-4-三氟甲基卤代苯和氰化亚铜摩尔比为1:0.5-3.0。
3.根据权利要求2所述的制备方法，其特征在于：2-硝基-4-三氟甲基卤代苯和氰化亚铜摩尔比为1:0.7-2.0。
4.根据权利要求1所述的制备方法，其特征在于：含氮有机碱与卤化物的摩尔比为1:0.1-3。
5.根据权利要求1所述的制备方法，其特征在于：其中催化剂由4-二甲氨基吡啶与碘化钾组成。
6.根据权利要求1所述的制备方法，其特征在于：2-硝基-4-三氟甲基卤代苯与催化剂总量摩尔比为1:0.05-1。
7.根据权利要求1所述的制备方法，其特征在于：所述溶剂为N,N-二甲基甲酰胺，N,N-二甲基乙酰胺、二甲基亚砜、N-甲基吡咯烷酮、环丁砜和苯腈中的一种或多种。
8.根据权利要求1所述的制备方法，其特征在于，所述精制包括步骤如下：取反应物降至室温，在搅拌下把溶液倒入浓度为40-50%的乙酸乙酯水溶液中，乙酸乙酯水溶液的用量为2-硝基-4-三氟甲基苯腈粗品摩尔量的4.0-8.0倍，过滤去除铜盐，滤饼用乙酸乙酯洗涤萃取，乙酸乙酯的用量为2-硝基-4-三氟甲基苯腈摩尔量的2-4倍，合并油层，再用水洗涤油层，最后用无水硫酸镁干燥后真空精馏，得到2-硝基-4-三氟甲基苯腈。
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