CN1293197A - Process for preparing (1-trifluoromethyl) ene boric acid and its application - Google Patents

Process for preparing (1-trifluoromethyl) ene boric acid and its application Download PDF

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CN1293197A
CN1293197A CN 00125767 CN00125767A CN1293197A CN 1293197 A CN1293197 A CN 1293197A CN 00125767 CN00125767 CN 00125767 CN 00125767 A CN00125767 A CN 00125767A CN 1293197 A CN1293197 A CN 1293197A
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trifluoromethyl
boric acid
aryl
ene boric
ene
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CN1093542C (en
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姜标
王全伏
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Research Center Of Organic Synthetic Engineering Chinese Academy Of Sciences
Shanghai Institute of Organic Chemistry of CAS
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Research Center Of Organic Synthetic Engineering Chinese Academy Of Sciences
Shanghai Institute of Organic Chemistry of CAS
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Abstract

A (1-trifluoromethyl) alkenyl boric acid is prepared through reaction of 1-trifluoromethyl-1-haloolefine, magnesium filings and trialkyl borate at 0 deg.C-ordinary temp. in organic ether solvent for 1-10 hr to obtain dialkyl (1-trifluoromethyl) alkenyl borate, and acid hydrolysis. Its advantages are simple process and easily available raw materials. The obtained reagent trifluoromethyl toron can take part in cross coupling reaction with halogen atoms on aromatic cycle or aromatic heterocycle under the catalysis of zero-valence Pd to generate organic compound containing (1-trifluoromethyl) alkenyl group.

Description

The preparation and the application thereof of (1-trifluoromethyl) ene boric acid
The present invention relates to the preparation and the application of fluorine-containing acid reagent, i.e. the preparation and the application of (1-trifluoromethyl) ene boric acid.
Because trifluoromethyl has very high electronegativity, stability and lipotropy, so the introducing of trifluoromethyl, in medicine, agricultural chemicals and bioactive molecules, special application is arranged all.Document J.Am.Chem.Soc.73,1042,1951 disclose the synthetic of 2-bromine trifluoro propene, since easy to prepare, be used as important fluorine-containing synthetic building block.The document J.Org.Chem.56 that Shanghai Organic Chemistry Institute, Chinese Academy of Sciences delivers, 7336-7340,1991 and J.Org.Chem.56,7336-7340,1991 have reported the preparation and the application of (1-trifluoromethyl) thiazolinyl zincon and (1-trifluoromethyl) thiazolinyl tin reagent respectively.Concrete reaction formula is as follows:
These two kinds of metal reagents all are quite stables under the condition of anhydrous and oxygen-free, and can be used to synthetic multiple important drugs intermediate.But, these two kinds of metal reagents are because all comparatively responsive to empty G﹠W, therefore relative higher to the requirement of reaction conditions and conversion unit, consider that the boric acid analogue has the response characteristic of above two kinds of metal reagents equally, and under the condition that the water aerobic is arranged quite stable, so we seek the synthetic method of (1-trifluoromethyl) ene boric acid reagent, be more convenient for further using in the hope of this synthetic building block, and finally can find the approach of a suitable suitability for industrialized production.
Purpose of the present invention just provides a kind of (1-trifluoromethyl) ene boric acid, its general molecular formula is:
R wherein 1=C nH 2n, n=1-4;
Another purpose of the present invention just provides a kind of method of synthetic (1-trifluoromethyl) ene boric acid, system is set out by corresponding 1-Trifluoromethyl-1-haloolefin, act in ether solvent with MAGNESIUM METAL and trialkyl borate, the method for the treatment of different things alike obtains accordingly (1-trifluoromethyl) ene boric acid dialkyl, makes accordingly (1-trifluoromethyl) ene boric acid through acid hydrolysis again.R wherein 1=C nH 2n, n=1-4; R 2=alkyl, phenyl; X=Cl, Br, I.Reaction formula is as follows:
Figure 0012576700052
The concrete reactions steps of the present invention is in ether organic solvent, under the condition of 0 ℃-room temperature, 1-Trifluoromethyl-1-haloolefin and MAGNESIUM METAL and trialkyl borate reaction obtain corresponding (1-trifluoromethyl) ene boric acid dialkyl, make accordingly (1-trifluoromethyl) ene boric acid through acid hydrolysis again.Wherein the reaction times is 1-10 hour; 1-Trifluoromethyl-1-haloolefin: MAGNESIUM METAL: the mol ratio of trialkyl borate is 1: 1-2: 1-2 is recommended as 1: 1.5: 1.5; Ether organic solvent is tetrahydrofuran (THF), ether, methyl tertiary butyl ether etc., and acid is HCl, H 2SO 4, HNO 3
The present invention also provides the purposes of this compounds, promptly (1-trifluoromethyl) ene boric acid and halo aromatic ring or halo virtue heterocycle carries out cross-coupling reaction under the catalysis of zeroth order palladium, synthesized a series of (1-trifluoromethyl) vinyl aromatic (co) heterogeneous ring compound, reaction formula is as follows:
Figure 0012576700061
Wherein zero valent palladium catalyst is Pd (PPh 3) 4, its consumption is 2%-10% mmol; Alkali is yellow soda ash or salt of wormwood, and organic solvent is a benzene,toluene,xylene; Reaction times is backflow 6-24 hour.Wherein X=Cl, Br, I; R 3=aryl, substituted aryl, heterocyclic aryl or substituted heterocycle aryl; Aryl or substituted aryl are
Figure 0012576700062
Heterocyclic aryl or substituted heterocycle aryl are
R wherein 4, R 5, R 6=H, Cl, NO 2, CN, F, CF 3, COOR 9, R 9, OR 9R 7, R 8=OH, NH 2, H, COOR 9, R 9, OR 9R 9=C 1-4Alkyl.
Trifluoromethyl borane reagent provided by the present invention-(1-trifluoromethyl) ene boric acid has stable properties under the condition that the water aerobic is arranged compared with prior art, it is easy that its preparation method not only reacts, raw material is easy to get, and is easy to operate, is a kind of method that is suitable for suitability for industrialized production.
Following examples help to understand the present invention, but do not limit content of the present invention.
Embodiment 1
With 10mmol 2-bromine trifluoro propene, the 15mmol MAGNESIUM METAL, the 15mmol tri-n-butyl borate is dissolved in the 20ml tetrahydrofuran (THF), at room temperature reacts 6 hours, and fluorine spectrum nuclear-magnetism shows almost Quantitative yield of fluorine-containing raw material.Rotary evaporation is removed solvents tetrahydrofurane, and residuum adds 10ml 2N dilute hydrochloric acid and stirs half an hour, with ether 3 * 20ml extraction.Merge organic layer, be washed to neutrality with saturated common salt, anhydrous sodium sulfate drying.Get (1-trifluoromethyl) vinyl boric acid di-n-butyl after steaming desolventizes, add hydrochloric acid hydrolysis and get (1-trifluoromethyl) vinyl boric acid, data are as follows: IR (KBr pellet): 3000,1750,1600,1346,1160, and 1120cm -1 1H?NMR(300MHz，CDCl 3)δ：1．00(t，J=8．0Hz，CH 3-)，1．29(s，C-H)ppm。 19F?NMR(60MHz，CDCl 3)δ：-21．8(s)ppm。
Embodiment 2 reactions steps are with embodiment 1
Figure 0012576700071
2-bromine trifluoro hexene 20mmol Trialkyl borate 0 ℃ Ether 10 hours (1-trifluoromethyl) butenyl boric acid 19NMR (CDCl 3: δ TFA-18.7 (s); IR:1195,1128 (CF 3) cm -1 1H NMR (CDCl 3): δ 6.25 (m, 3H), 7.09 (q, J=1.4Hz, 1H), 8.63 (m, 2H).
Embodiment 3
With the 10mmol aryl halide, 12mmol (1-trifluoromethyl) vinyl boric acid dialkyl, 0.02mmol Pd (PPh 3) 4, 1ml 1M Na 2CO 3, 10ml toluene places under the nitrogen atmosphere, backflow 6-24 hour.Reaction adds water 10ml after finishing, with ether 3 * 10ml extraction.Merge organic layer, be washed to neutrality with saturated common salt, anhydrous sodium sulfate drying.Steaming desolventizes after distillation, recrystallization or column chromatography get pure product, and compound sees the following form.
Embodiment 4
With 10mmol 2-amino-3-methoxyl group-5-bromine, 12mmol (1-trifluoromethyl) vinyl boric acid dialkyl, 0.02mmol Pd (PPh 3) 4, 1ml 1M Na 2CO 3, 10ml toluene places under the nitrogen atmosphere, backflow 6-24 hour.Reaction adds water 10ml after finishing, with ether 3 * 10ml extraction.Merge organic layer, be washed to neutrality with saturated common salt, anhydrous sodium sulfate drying.Steaming desolventizes after column chromatography or recrystallization get pure product, and compound sees the following form.
Figure 0012576700091
Compound 1
IR：1580，1500，1380cm -1；
19F?NMR?δ-11．0ppm(s，CF 3)；
1H?NMR：δ?7．45(m．5H)，5．96(s，1H)，5．77(s，1H)；
MS，m／e：172(M +)；
Ultimate analysis C 9H 7F 3
Calculated value: C62.79, H4.01;
Measured value: C62.37, H4.25.
Compound 2
IR：1575，1475，1423，1322，1303cm -1；
19F?NMR：δ-11．0ppm(s，3F)，-13．0ppm(s，3F)；
1H?NMR：δ7．73(s，1H)，7．58(m，3H)，6．06(s，1H)，5．84(s，1H)；
MS，m／e：240(M +)；
Ultimate analysis C 9H 7F 3:
Calculated value: C50.00, H2.50;
Measured value: C50.19, H2.46.
Compound 3
IR：1614，1438，1407，1353，1318cm -1；
19F?NMRδ-11．5ppm(s，CF 3)；
1H?NMR：δ8．06(d，J=8．2Hz，2H)，7．54(d，J=8．2Hz，2H)，6．05(s，1H)，5．87(s，1H)，3．94(s，3H)；
MS，m／e：230(M +)；
C 11H 9F 3O 2Calculated value: C57.39, H3.91;
Measured value: C57.57, H3.86.
Compound 4:
IR：1606，1568，1533，1475，1411，1386cm -1；
19F?NMRδ-11．5ppm(s，CF 3)；
1H?NMR：δ8．03(d，J=8．8Hz，1H)，7．57(dd，J 1=8．8Hz，J 2=2．3Hz?1H)，7．42(d，J=2．3Hz，1H)，6．15(s，1H)，5．67(s，1H)；
MS，m／e：251(M +)；
Ultimate analysis C 9H 5F 3ClNO 2: calculated value: C, 43.03%, H, 1.99%, N, 5.38%;
Measured value: C, 43.04%, H, 1.98%, N, 5.60%.
Compound 5:
IR：1624，1533，1502，1451，1351cm -1；
19F?NMRδ-11．0ppm(s，CF 3)；
1H?NMR：δ8．08(d，J=1．7Hz，1H)，7．60(d，J=8．0Hz，1H)，7．39(d，J=8．0Hz，1H)；
MS：m／e，231(M +)；
Ultimate analysis C 10H 8F 3NO 2:
Calculated value: C51.95, H3.46, N6.06;
Measured value: C51.82, H3.35, N6.15.
Compound 6
IR：1610，1580，1510，1338cm -1；
19F?NMRδ-10．0ppm(s，CF 3)；
1H?NMRδ?7．87(m，3H)，7．50(m，4H)，6．35(s，1H)，5．68(s，1H)；
MS，m／e：222(M +)；
Ultimate analysis C 13H 9F 3:
Calculated value: C70.27, H4.05;
Measured value: C70.35, H4.12.
Compound 7
IR：3497，3297，3148，1639，1560，1516，1448，1427，1400，1359cm -1：
19F?NMRδ-13．0ppm(s，CF 3)；
1H?NMRδ7．69(s，1H)，6．42(s，1H)，5．91(s，1H)，3．23(s，3H)；
MS (m/z) 219 (M +); Ultimate analysis
C 8H 8F 3N 3O 2：
Calculated value: C43.84, H3.65, N19.18;
Measured value: C43.95, H3.52, N19.27.

Claims (6)

1, a kind of (1-trifluoromethyl) ene boric acid is characterized in that general molecular formula is: R wherein 1=C nH 2n, n=1-4.
2, a kind of method of synthetic (1-trifluoromethyl) ene boric acid, it is characterized in that under the condition of 0 ℃-room temperature, in ether organic solvent, 1-Trifluoromethyl-1-haloolefin and MAGNESIUM METAL and trialkyl borate reaction obtain corresponding (1-trifluoromethyl) ene boric acid dialkyl, make accordingly (1-trifluoromethyl) ene boric acid through acid hydrolysis again; Reaction formula is as follows:
R wherein 1=C nH 2n, n=1-4; R 2=alkyl, phenyl; X=Cl, Br, I; Reaction times is 1-10 hour; Acid is HCl, H 2SO 4, HNO 31-Trifluoromethyl-1-haloolefin: MAGNESIUM METAL: the mol ratio of trialkyl borate is 1: 1-2: 1-2,
3, the method for synthetic (1-trifluoromethyl) ene boric acid as claimed in claim 1 or 2 is characterized in that ether organic solvent comprises tetrahydrofuran (THF), ether, methyl tertiary butyl ether.
4, the method for synthetic (1-trifluoromethyl) ene boric acid as claimed in claim 1 or 2, it is characterized in that 1-Trifluoromethyl-1-haloolefin: MAGNESIUM METAL: the mol ratio of trialkyl borate is 1: 1.5: 1.5;
5, the purposes of a kind of (1-trifluoromethyl) ene boric acid, it is characterized in that (1-trifluoromethyl) ene boric acid and halo aromatic ring or halo virtue heterocycle carries out cross-coupling reaction under the catalysis of zeroth order palladium, synthesized a series of (1-trifluoromethyl) vinyl aromatic (co) heterogeneous ring compound, reaction formula is as follows: Wherein X=Cl, Br, I; R 3=aryl, substituted aryl, heterocyclic aryl or substituted heterocycle aryl; Zero valent palladium catalyst is Pd (PPh 3) 4, its consumption is 2%-10% mmol; Alkali is yellow soda ash or salt of wormwood, and organic solvent is a benzene,toluene,xylene; Reaction times is backflow 6-24 hour.
6, the purposes of (1-trifluoromethyl) as claimed in claim 5 ene boric acid is characterized in that aryl or substituted aryl are Heterocyclic aryl or substituted heterocycle aryl are
R wherein 4, R 5, R 6=H, Cl, NO 2, CN, F, CF 3, COOR 9, R 9, OR 9R 7, R 8=OH, NH 2, H, COOR 9, R 9, OR 9R 9=C 1-4Alkyl.
CN00125767A 2000-10-25 2000-10-25 Process for preparing (1-trifluoromethyl) ene boric acid and its application Expired - Fee Related CN1093542C (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7964758B2 (en) 2006-02-13 2011-06-21 Nissan Chemical Industries, Ltd. Process for production of 2-(substituted phenyl)-3,3,3-trifluoropropene compound
CN103601744A (en) * 2013-11-26 2014-02-26 大连联化化学有限公司 Method for preparing 2,2-dimethyl vinyl boric acid
CN104478918A (en) * 2014-12-31 2015-04-01 大连联化化学有限公司 Synthesis method of cycloalkene-1-boronic acid pinacol ester

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1112347C (en) * 1999-12-29 2003-06-25 中国科学院上海有机化学研究所 1-trifluoromethyl-2-alkylvinylaniline derivative and its synthesis

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7964758B2 (en) 2006-02-13 2011-06-21 Nissan Chemical Industries, Ltd. Process for production of 2-(substituted phenyl)-3,3,3-trifluoropropene compound
CN103601744A (en) * 2013-11-26 2014-02-26 大连联化化学有限公司 Method for preparing 2,2-dimethyl vinyl boric acid
CN103601744B (en) * 2013-11-26 2016-03-09 大连联化化学有限公司 One prepares the method for 2,2-dimethylvinylsiloxy ylboronic acid
CN104478918A (en) * 2014-12-31 2015-04-01 大连联化化学有限公司 Synthesis method of cycloalkene-1-boronic acid pinacol ester

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