CN1140713A - Single synthetic method for trifluoromethyl pyrroles compound - Google Patents
Single synthetic method for trifluoromethyl pyrroles compound Download PDFInfo
- Publication number
- CN1140713A CN1140713A CN 95111694 CN95111694A CN1140713A CN 1140713 A CN1140713 A CN 1140713A CN 95111694 CN95111694 CN 95111694 CN 95111694 A CN95111694 A CN 95111694A CN 1140713 A CN1140713 A CN 1140713A
- Authority
- CN
- China
- Prior art keywords
- trifluoromethyl
- compounds
- oxazolone
- alkali
- pyrpole
- 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
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
At room temp, triflluoromethyl oxazolone and organic dihalide are synthesized into pyrrole trifluoride compound in the presense of organic solvent and alkali. The said method has mild reaction condition, simple operation and high yield.
Description
The present invention relates to a kind of synthetic method of fluorine-containing heterocyclic organic compounds, specifically is exactly a kind of method of directly synthesizing the trifluoromethyl pyrpole compounds by San Fu Jia oxazolones single step reaction.
The biological activity of trifluoromethyl pyrpole compounds and their application prospects on medicine and agricultural chemicals are subjected to people's attention (Welch.J.H.Tetrahedron, 43,3123,1987 more and more; Filler.R.etal, " Biomedicinal Aspect of FlourineChemistry ", Kodasha Ltd.Tokyo, 1982; Yoshika.H.et al, Syn.Chem.Jpn.42,809,1984; Whr.H.etal, Ger.Offen.DE.4,217,722,02 Dec1993; Outcalt.R.J.etal, US.5,187,185,16Feb1993.).The trifluoromethyl pyrpole compounds also just is being developed to a class novel pesticide and miticide (Chem.﹠amp; I ＇ nd.773,1990).But the groups such as methyl, trichloromethyl or carboxyl that directly the heterocycle molecule carried out trifluoromethylation and transform the heterocycle molecule that adopt at present usually become the method for trifluoromethyl, not only reactions steps is many, complex operation, and total recovery is low, and reaction is adopted and fluoridized or trifluoromethyl reagent costs an arm and a leg and tool toxicity.Tian Weisheng etc. have reported 1 of one three fluorine first oxazolones and activatory carbon-to-carbon unsaturated bond, method (the Weisheng Tian etal of the synthetic trifluoromethyl pyrpole compounds of 3-Dipolar Cycloaddition, CCI, 2,219,1991) .93 Tian Weisheng etc. has also applied for the process patent (CN92108305.X) of " a kind of method from the synthetic trifluoromethyl pyrpole compounds of three fluorine first oxazolones ", this method is in the presence of alkali, San Fu Jia oxazolones and activatory carbon-to-carbon unsaturated compound at room temperature get the trifluoromethyl pyrpole compounds by Mannich addition and decarboxylic reaction, and reaction is shown below:
This synthetic method responds that step is few, the advantage of mild condition, yield height.We continue to explore a kind of more economical method of synthetic trifluoromethyl pyrpole compounds effectively on this basis.
It is the raw material economics method of synthetic trifluoromethyl pyrpole compounds effectively with the trifluoromethyl oxazolone that purpose of the present invention just provides a kind of.
Synthetic method of the present invention is that trifluoromethyl oxazolone and dihalo-organic compound are in organic solvent under the condition that alkali exists, and room temperature is reacted and can directly be obtained the trifluoromethyl pyrpole compounds.Be shown below:
Concrete grammar of the present invention is to be with molecular formula
Trifluoromethyl oxazolone and molecular formula be
The dihalo-organic compound is in organic solvent, and at ambient temperature, the preparation molecular formula is under the effect of alkali
The trifluoromethyl pyrpole compounds.Wherein R and R1 be replace, replace, alkyl (n=1-10), aromatic ring yl or the heterocyclic radical of straight or branched Cn, described aromatic ring yl can be phenyl, alkyl phenyl, benzyl, nitrophenyl, p-methoxy-phenyl, halogenophenyl, naphthyl.Heterocyclic radical can be pyridyl, pyranyl, furyl.EWG is an electron-withdrawing group, can be cyano group, isocyano-, nitro, ester group, ketone group, trifluoromethyl, alkyl sulphonyl, phosphonate group, and X is a halogen, as chlorine, bromine.The mole ratio of above-mentioned trifluoromethyl oxazolone, dihalo-organic compound and alkali is 1: 1-10: 1-10 is recommended as 1: 1-5: 1-5.The mole ratio of dihalo-organic compound and alkali equivalent preferably wherein, but excessively do not influence reaction.
Molecular formula required for the present invention is
The dihalo-organic compound can be easily addition reaction by alkene and chlorine or bromine obtain.
The organic solvent that the present invention reacts used can be toluene, dimethylbenzene, benzene, acetonitrile, methylene dichloride, chloroform, tetrahydrofuran (THF), ether, glycol dimethyl ether, tetracol phenixin.Reaction is to help present method invention in above-mentioned organic solvent, and what of its consumption there is no much influences to reaction, can the solubilizing reaction thing can but not as limit.
The present invention react described alkali be 1.8-diaza-bicyclo " 5.4.0 " 11-7-alkene, 1.5-diaza-bicyclo " 4.3.0 " ninth of the ten Heavenly Stems-5-alkene, 1.4-diaza-bicyclo " 2.2.2 " octane, ethyl diisopropylamine, triethylamine, sodium hydride, N.N-Diethyl Aniline.
In at least 0.5 hour reaction times of present method invention, be generally 0.5-48 hour.The length in reaction times will influence the yield of the finished product, and the yield of reaction is 25%-95%.
Present method invention is compared with existing patent with existing technology, possessed not only that reactions steps is few, mild condition, easy and simple to handle and characteristics that yield is high, also because used the dihalo-organic compound that can obtain by simple alkene addition reaction, therefore also have cost-effective advantage, make it agricultural chemicals and medical aspect applicating and exploitation more have practical value and bright prospects.
Following embodiment will help to understand the present invention, but be not limited to the present invention.
(229mg, 1mmol), 1,8-diaza-bicyclo [5,4,0] 11-7-alkene drips 0.12ml 2 to embodiment 12-trifluoromethyl-4-itrile group-5-phenylpyrrole (3a) dissolving trifluoromethyl oxazolone in the 5ml acetonitrile, behind 3-two bromopropionitriles, room temperature reaction 1 hour.Concentrate, add water, use dichloromethane extraction.Extracting solution concentrates after washing, and column chromatography for separation gets 2-trifluoromethyl-4-itrile group-5-phenylpyrrole 165mg, white, productive rate 70%.m.p.218-219℃.IR(film)ν：3200(N-H)，2400(CN)cm
-1.
1H-NMRδ：7.78(2H，dd，J＝8，1.6Hz，Ar-H)，7.54(3H，m，Ar-H)，7.28(1H，brs)ppm.
19F-NMR：-17(s，CF
3)ppmMS：236(M
+)，216(M-HF)，197(M-HF-F).
Embodiment 2 implementation conditions are as described in the embodiment 1, difference and the results are shown in Table 1.2-trifluoromethyl-5-phenyl-pyrroles-m.p.108-110 ℃ of IR ν of 4-methyl-formiate (3b) (KCl): 3250 (N-H); 1680 (C=O); 1470 (Pyrrol C=C); 1260 (COOR) cm
-1.
1H-NMR δ: 8.7 (1H, brs, N-H), 7.6 (2H, m, Ar-H), 7.4 (3H, m, Ar-H), 7.1 (1H, m, Pyrrole-H), 3.s, CO
2CH
3) ppm.
19F-NMR (EtOAc) δ :-16 (s, ppm.MS:269 (M
+), 270 (M+1), 238 (M-OCH
3), 218 (M-OCH
3-HF) .C
13H
10F
3NO
2HRMS:C
13H
10F
3NO
2, 269.0633 ,-3.0/1002-trifluoromethyl-3-methyl-5-phenylpyrrole-m.p.144-145 ℃ of IR of 4-methyl-formiate (3c) (film) ν: 3200 (N-H), 1680 (C=O), 1460 (Pyrrole C=C), 1380,1270,1210cm
-1.
1H-NMR δ: 7.4 (5H, m, Ar-H), 3.7 (3H, s, OCH
3), 2.4 (3H, s, CH
3), 8.4 (1H, brs, N-H) ppm.
19F-NMR (EtOAc) δ :-18 (s, CF
3) ppm.MS:283 (M
+), 284 (M+1), 252 (M-OCH
3), 232 (M-OCH
3-HF, 34) .HRMS:C
14H
12F
3NO
2, 283.0840,2.0/1002-trifluoromethyl-3,5-phenylbenzene pyrroles-m.p.141-142 ℃ of IR of 4-methyl-formiate (3d) (film) ν: 3250 (N-H), 1690 (C=O), 1450,1390,1220cm
-1.
1H-NMR δ: 8.7 (1H, brs, N-H), 7.3-7.6 (10H, m, Ar-H), 3.5 (3H, s, OCH
3) ppm.
19F-NMR (CH
2Cl
2) δ :-21.5 (s, CF
3) ppm.MS:345 (M
+), 314 (M-OCH
3), 294 (M-OCH
3-HF). ultimate analysis Calc.C66.07, H4.08, N4.05
FoundC66.02, H4.41, N3.552,4-couple-trifluoromethyl-5-phenylpyrrole (3e) IR (film) ν: 3250 (N-H), 1720,1600,1500 (pyrrole C=C) cm
-1.
1H-NMR δ: 8.4-9.1 (1H, brs, Pyrrole-H), 7.3-7.5 (8H, m, Ar), 6.8-7.0 (2H, m, Ar) ppm
19F-NMR (CH
2Cl
2) δ :-23 (s, CF
3) ,-18 (s, CF
3) ppm.MS:279 (M
+), 260 (M-F), 258 (M-l-HF) .2,4-couple-trifluoromethyl-5-p-methoxyphenyl pyrroles (3f) IR (film) ν: 3250 (N-H), 1610,1500 (s, pyrrole C=C), 1270,1120cm
-1.
1H-NMR δ: 7.2-7.5 (2H, m, Ar-H), 6.8-7.1 (2H, m, Ar-H), 4.9-5.5 (1H, brs, N-H), 3.9 (3H, s, OCH
3), 2.6-3.0 (1H, Pyrrol-H) ppm.
19F-NMR (CH
2Cl
2) δ :-18 (s, CF
3) ,-13 (s, CF
3) ppm.MS:309 (M
+) .HRMS:C
13H
9F
6NO, 309.209,1.8/1000
Table 1
Entry R R ' EWG solvent time (hrs) yield (%) a Ph H CN toluene 2 70%b Ph H CO
2CH
3CH
3CN 1 31%c Ph CH
3CO
2CH
3Toluene 1 58%d Ph Ph CO
2CH
3Toluene 2 62%e Ph H CF
3CH
3CN 2 90%f p-CH
3OPh H CF
3Toluene 5 82%
Claims (4)
1. one kind from molecular formula is
Simple and effective ground of trifluoromethyl oxazolone synthetic molecules formula be
Trifluoromethyl pyrpole compounds method, it is characterized in that directly being by trifluoromethyl oxazolone and molecular formula
The dihalo-organic compound under organic solvent and alkali existence condition, carry out the room temperature building-up reactions and obtain the trifluoromethyl pyrpole compounds, wherein R and R
1Be replace, replace, alkyl (n=1-10), aromatic ring yl or the heterocyclic radical of straight or branched Cn, described aromatic ring yl can be phenyl, alkyl phenyl, benzyl, nitrophenyl, p-methoxy-phenyl, halogenophenyl, naphthyl.Heterocyclic radical can be pyridyl, pyranyl, furyl.EWG is an electron-withdrawing group; can be cyano group, isocyano-, nitro, ester group, ketone group, trifluoromethyl, alkyl sulphonyl, phosphonate group; X is a halogen, and as chlorine, bromine, the mole ratio of described trifluoromethyl oxazolone, dihalo-organic compound and alkali is 1: 1-10: 1-10.
2. the method for a synthetic trifluoromethyl pyrpole compounds as claimed in claim 1, the mole ratio that it is characterized in that described trifluoromethyl oxazolone, dihalo-organic compound and alkali is 1: 1-5: 1-5.
3. the method for a synthetic trifluoromethyl pyrpole compounds as claimed in claim 1 or 2, it is characterized in that described alkali be 1.8-diaza-bicyclo " 5.4.0 " 11-7-alkene, 1.5-diaza-bicyclo " 4.3.0 " ninth of the ten Heavenly Stems-5-alkene, 1.4-diaza-bicyclo " 2.2.2 " octane, ethyl diisopropylamine, triethylamine, sodium hydride, N.N-Diethyl Aniline.
4. the method for a synthetic trifluoromethyl pyrpole compounds as claimed in claim 1 or 2 is characterized in that described organic solvent is toluene, dimethylbenzene, benzene, acetonitrile, methylene dichloride, chloroform, tetrahydrofuran (THF), ether, glycol dimethyl ether, tetracol phenixin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 95111694 CN1140713A (en) | 1995-07-17 | 1995-07-17 | Single synthetic method for trifluoromethyl pyrroles compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 95111694 CN1140713A (en) | 1995-07-17 | 1995-07-17 | Single synthetic method for trifluoromethyl pyrroles compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1140713A true CN1140713A (en) | 1997-01-22 |
Family
ID=5078955
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 95111694 Pending CN1140713A (en) | 1995-07-17 | 1995-07-17 | Single synthetic method for trifluoromethyl pyrroles compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1140713A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110382462A (en) * | 2017-03-13 | 2019-10-25 | 巴斯夫农业公司 | Aryl-pyrrole compound is produced in the presence of DIPEA alkali |
-
1995
- 1995-07-17 CN CN 95111694 patent/CN1140713A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110382462A (en) * | 2017-03-13 | 2019-10-25 | 巴斯夫农业公司 | Aryl-pyrrole compound is produced in the presence of DIPEA alkali |
| JP2020511458A (en) * | 2017-03-13 | 2020-04-16 | ビーエーエスエフ アグロ ベー．ブイ． | Preparation of arylpyrrole compounds in the presence of DIPEA base |
| JP7260480B2 (en) | 2017-03-13 | 2023-04-18 | ビーエーエスエフ アグロ ベー．ブイ． | Preparation of Arylpyrrole Compounds in the Presence of DIPEA Base |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Pu et al. | Doubly stereocontrolled asymmetric conjugate addition of acetylacetone to nitroolefins catalyzed by bifunctional tertiary amine–thiourea catalysts derived from both acyclic α-amino acids and carbohydrates | |
| CN102153557B (en) | Chiral center nitrogen heterocyclic carbine precursor salt with quadrol skeleton, synthetic method and application | |
| Fraile et al. | Synthesis and reactivity of 5-methylenehydantoins | |
| US7417142B2 (en) | Chiral porphyrins, chiral metalloporphyrins, and methods for synthesis of the same | |
| Licandro et al. | Enantioselective synthesis of (R)-(−)-baclofen using Fischer-type carbene anions | |
| Shin et al. | Stereoselective synthesis of enantiomerically pure d-threo-PDMP; manipulation of a core 2, 3-diamino alcohol unit | |
| Luo et al. | Asymmetric synthesis of O-alkylated tetronic acid derivatives via an organocatalytic Mannich reaction and subsequent intramolecular cyclization | |
| Kimura et al. | A new synthetic method for the preparation of α, β-didehydroamino acid derivatives by means of a Wittig-type reaction. Syntheses of (2 S, 4 S)-and (2 R, 4 R)-4-hydroxyprolines | |
| Hercouet et al. | Asymmetric synthesis of a phosphonic analogue of (−)-allo-norcoronamic acid | |
| Han et al. | Chiral N‐phosphonyl imine chemistry: asymmetric additions of ester enolates for the synthesis of β‐amino acids | |
| Mollet et al. | Stereoselective synthesis of bicyclic tetrahydrofuran-fused β-lactams and their conversion into methyl cis-3-aminotetrahydrofuran-2-carboxylates | |
| Sha et al. | Detrifluoroacetylative cascade reactions of bicyclic fluoro-enolates with ortho-phthalaldehyde: Aspects of reactivity, diastereo-and enantioselectivity | |
| CN1140713A (en) | Single synthetic method for trifluoromethyl pyrroles compound | |
| EP2655322A1 (en) | Process for preparing chiral amino acids | |
| Tanaka et al. | Asymmetric synthesis of γ-alkayl-α-methylene-γ-butyrolactones via 1, 6-remote induction using 2-[(tributylstannyl) methyl] propenamides | |
| Catasús et al. | Sulphur ylide-mediated stereoselective synthesis of a stable ferrocenyl epoxide | |
| WO2015189862A1 (en) | Chiral amines, a process for preparation and use thereof | |
| Enders et al. | Efficient asymmetric synthesis of 3-substituted β-sultams | |
| Chen et al. | Pictet-Spengler Cyclization of 3, 3-Diphenylalanine (DIP)(III), Synthesis of Optically Pure 1, 2, 3, 4-Tetrahydro-4-Phenyl-3-Isoquinolinecarboxylic Acids, Novel α-Amino Acids for Peptides of Biological Interest | |
| JPH0692945A (en) | Production of cyclic urethane compound | |
| Barluenga et al. | Catalytic imino-Diels–Alder reactions of 2-aminodienes: a simple entry into structurally diverse pipecolic acid derivatives | |
| Dell'Erba et al. | Synthetic exploitation of the ring‐opening of 3, 4‐dinitrothiophene. Part 4. Synthesis of 1, 4‐disubstituted 3‐hydroximino‐2‐nitro‐1‐butenes and their cyclization to 4‐nitroisoxazoles | |
| US5654461A (en) | Sulfamate compound containing carbamoyl group | |
| Zheng | Lewis Base Catalyzed Electrophilic Transformations | |
| CN1093539C (en) | Process for synthesizing beta-halobutenolide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |