CN100376582C - Process for preparing hexahydro furyl [3,2-c] quinoline derivatives - Google Patents
Process for preparing hexahydro furyl [3,2-c] quinoline derivatives Download PDFInfo
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- CN100376582C CN100376582C CNB2006100505213A CN200610050521A CN100376582C CN 100376582 C CN100376582 C CN 100376582C CN B2006100505213 A CNB2006100505213 A CN B2006100505213A CN 200610050521 A CN200610050521 A CN 200610050521A CN 100376582 C CN100376582 C CN 100376582C
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- China
- Prior art keywords
- arylamine
- iodine
- reaction
- hexahydro furyl
- quinoline
- Prior art date
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Links
- 125000002541 furyl group Chemical group 0.000 title claims description 22
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title abstract 3
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 150000004982 aromatic amines Chemical class 0.000 claims abstract description 20
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 claims abstract description 15
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 11
- 239000011630 iodine Substances 0.000 claims abstract description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 10
- 230000035484 reaction time Effects 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 36
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000006555 catalytic reaction Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 8
- 238000010189 synthetic method Methods 0.000 abstract description 7
- -1 iodine, arylamine Chemical class 0.000 abstract description 2
- 229910052755 nonmetal Inorganic materials 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract 2
- 230000003197 catalytic effect Effects 0.000 abstract 1
- 238000000605 extraction Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000003260 anti-sepsis Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 1
- 229940055742 indium-111 Drugs 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000007226 seed germination Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention discloses a method for preparing a hexahydro furan [3, 2-c] chinoline derivative, which comprises: under the catalytic action of iodine, arylamine reacts with 2, 3-dihydro furan in organic solvent at room temperature, and the reaction time is from 3 to 15 minutes; after simple extraction and separation, a hexahydro furan [3, 2-c] chinoline derivative is obtained, wherein the molar equivalent ratio of the arylamine to the 2, 3-dihydro furan is (0.4 to 0.6) to 1, and the dosage of the catalyst (iodine) accounts for 0.05 to 0.2 of the molar equivalent of the arylamine. Compared with the existing synthetic method, the present invention has the following advantages: 1) the reaction conditions are mild, the reaction is carried out without isolating air, and the reaction time is short; 2) non-metal (iodine) is used as a catalyst; 3) the processes of material charge and post treatment are simple, and the cost is low, and the present invention has good application prospects.
Description
Technical field
The present invention relates to the nitrogen heterocyclic ring synthetic method, relate in particular to the synthetic method of a kind of hexahydro furyl [3,2-c] quinoline.
Background technology
Quinoline is one of modal structure component in the natural product, has multiple important physical activity.For example, antisepsis and anti-inflammation, antimycotic, antitumor, and regulate seed germination and plant-growth etc., at aspects such as medicine and agricultural chemicals huge value of exploiting and utilizing is arranged.Although the synthetic method of hexahydro furyl [3,2-c] quinoline has had a lot of reports, for example, (1) document J.Org.Chem.2002,67, reported Indium-111 chloride catalysis arylamine and 2 among the 3969-3971, the method of 3-dihydrofuran prepared in reaction hexahydro furyl [3,2-c] quinoline; (2) Tetrahedron Letters, 2001,42,7935-7939 has reported the method for trifluoromethanesulfonic acid metal species catalysis arylamine and 2,3 dihydro furan prepared in reaction hexahydro furyl [3,2-c] quinoline; (3) Green Chem.2003,5,627-629 has reported the method for acidic ion exchange resin catalysis arylamine and 2,3 dihydro furan prepared in reaction hexahydro furyl [3,2-c] quinoline.But document reported method maybe will use expensive reagent, or has provided unfavorable productive rate, or will the very long reaction times, or wants relatively large catalyzer or the like.Therefore it is very important seeking easy hexahydro furyl quick, with low cost [3,2-c] quinoline preparation method.
Summary of the invention
The synthetic method that the purpose of this invention is to provide a kind of hexahydro furyl [3,2-c] quinoline.
It is under catalysis of iodine, in organic solvent, and arylamine and 2,3 dihydro furan reaction, the reaction times is 3-15 minute, obtains hexahydro furyl [3,2-c] quinoline through extracting and separating, arylamine and 2, the molar equivalent ratio of 3-2 hydrogen furans is 0.4-0.6: 1; The consumption of catalyzer iodine is the 0.05-0.2 molar equivalent of arylamine; Reaction formula is:
Wherein X=H, halogen, alkyl or alkoxyl group, wherein alkyl is C
nH
2n+1, n=1-4.Said organic solvent is 1,2-ethylene dichloride, benzene, toluene, acetonitrile, tetrahydrofuran (THF) or methylene dichloride; The reaction room temperature is 15-40 ℃; Reaction times is 4-10 minute.Said arylamine and and the molar equivalent ratio of 2,3 dihydro furan be 0.45-0.55: 1; The consumption of catalyzer iodine is the 0.08-0.15 molar equivalent of arylamine.
The present invention compares with existing synthetic method, has advantage under the M:
1) the reaction conditions gentleness is reacted without secluding air, and the reaction times is short;
2) use nonmetal eka iodine to make catalyzer;
3) feed intake and aftertreatment all very simple, with low cost, good prospects for application is arranged.
Specific implementation method
Hexahydro furyl [3,2-c] quinoline general molecular formula is:
Wherein X=H, halogen, alkyl, alkoxyl group, wherein alkyl is C
nH
2n+1, n=1-4.
The mechanism process of cyclization is:
The concrete reactions steps of the synthetic method of hexahydro furyl [3,2-c] quinoline is as follows:
Under catalysis of iodine, in organic solvent, arylamine and 2, the 3-dihydrofuran at room temperature reacts, and the reaction times is 3-15 minute, obtains hexahydro furyl [3 through simple extracting and separating, 2-c] quinoline, the molar equivalent ratio of arylamine and 2,3 dihydro furan is 0.4-0.6: 1; The consumption of catalyzer iodine is the 0.05-0.2 molar equivalent of arylamine.The recommendation response temperature is 20 ℃; The recommendation response time is 5 minutes.
Wherein organic solvent comprises 1,2-ethylene dichloride, benzene, toluene, acetonitrile, tetrahydrofuran (THF), methylene dichloride; Arylamine and and the molar equivalent ratio of 2,3 dihydro furan be 0.4-0.6: 1, the recommendation ratio is 0.45-0.55: 1; The consumption of catalyzer iodine is the 0.05-0.2 molar equivalent of arylamine, and recommending consumption is the 0.08-0.15 molar equivalent.
Following examples will help to understand the present invention, but be not limited to content of the present invention:
Embodiment 1
In reaction flask, add 10 mmole aniline, 20 mmole 2,3 dihydro furans, 20 milliliters of methylene dichloride and 1 mmole iodine successively, in room temperature (20 ℃) reaction 5 minutes down, finish reaction, with 10 milliliter of 10% hypo solution washing, isolate organic phase then, use anhydrous sodium sulfate drying, filter, filtrate concentrating obtains 3-(hexahydro furyl [3,2-c] quinolyl-4)-propyl alcohol, productive rate 93%.
IR(neat)：v＝3345，2931，1618，1501，1063cm
-1.
MS(ESI)：m/z＝233[M
+].
HRMS(EI)：m/z[M
+]calcd?for?C
14H
19NO
2：233.1416；found：233.1421.
Embodiment 2
In reaction flask, add 10 mmoles successively to monomethylaniline, 21 mmole 2,3 dihydro furans, 20 milliliters of benzene and 1.5 mmole iodine, in room temperature (30 ℃) reaction 3 minutes down, finish reaction, with 15 milliliter of 10% hypo solution washing, isolate organic phase then, use anhydrous sodium sulfate drying, filter, filtrate concentrating obtains 3-(8-methyl-hexahydro furyl [3,2-c] quinolyl-4)-propyl alcohol, productive rate 89%.
IR(neat)：v＝3347，2933，1618，1501，1063cm
-1.
MS(ESI)：m/z＝247[M
+].
HRMS(EI)：m/z[M
+]calcd?for?C
15H
21NO
2：247.1572；found：247.1578.
Embodiment 3
In reaction flask, add 10 mmole P-nethoxyaniline, 19 mmole 2,3 dihydro furans, 20 milliliters of toluene and 1.1 mmole iodine successively, in room temperature (25 ℃) reaction 5 minutes down, finish reaction, with 12 milliliter of 10% hypo solution washing, isolate organic phase then, use anhydrous sodium sulfate drying, filter, filtrate concentrating obtains 3-(8-methoxyl group-hexahydro furyl [3,2-c] quinolyl-4)-propyl alcohol, productive rate 85%.
IR(neat)：v＝3345，2931，1619，1503，1065cm
-1.
MS(ESI)：m/z＝263[M
+].
HRMS(EI)：m/z[M
+]calcd?for?C
15H
21NO
3：263.1521；found：263.1529.
Embodiment 4
In reaction flask, add 10 mmole para-bromoaniline, 20 mmole 2,3 dihydro furans, 20 milliliter 1 successively, 2-ethylene dichloride and 1 mmole iodine, reacted 5 minutes down in room temperature (25 ℃), finish reaction, then with 10 milliliter of 10% hypo solution washing, isolate organic phase, use anhydrous sodium sulfate drying, filter, filtrate concentrating obtains 3-(8-bromo-hexahydro furyl [3,2-c] quinolyl-4)-propyl alcohol, productive rate 82%.
IR(neat)：v＝3344，2938，1619，1508，1061cm
-1.
MS(ESI)：m/z＝311[M
+].
HRMS(EI)：m/z[M
+]calcd?for?C
14H
18BrNO
2：311.0521；found：311.0515.
Claims (4)
1. hexahydro furyl [3,2-c] preparation method of quinoline, it is characterized in that, under catalysis of iodine, in organic solvent, arylamine and 2,3 dihydro furan reaction, the reaction times is 3-15 minute, obtain hexahydro furyl [3 through extracting and separating, 2-c] quinoline, the molar equivalent ratio of arylamine and 2,3 dihydro furan is 0.4-0.6: 1; The consumption of catalyzer iodine is the 0.05-0.2 molar equivalent of arylamine; Reaction formula is:
Wherein X=H, halogen, alkyl or alkoxyl group, wherein alkyl is C
nH
2n+1, n=1-4.
2. the preparation method of a kind of hexahydro furyl according to claim 1 [3,2-c] quinoline is characterized in that said organic solvent is 1,2-ethylene dichloride, benzene, toluene, acetonitrile, tetrahydrofuran (THF) or methylene dichloride.
3. the preparation method of a kind of hexahydro furyl according to claim 1 [3,2-c] quinoline is characterized in that the said reaction times is 4-10 minute.
4. the preparation method of a kind of hexahydro furyl according to claim 1 [3,2-c] quinoline, the molar equivalent ratio that it is characterized in that said arylamine and 2,3 dihydro furan is 0.45-0.55: 1; The consumption of catalyzer iodine is the 0.08-0.15 molar equivalent of arylamine.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100505213A CN100376582C (en) | 2006-04-26 | 2006-04-26 | Process for preparing hexahydro furyl [3,2-c] quinoline derivatives |
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|---|---|---|---|
| CNB2006100505213A CN100376582C (en) | 2006-04-26 | 2006-04-26 | Process for preparing hexahydro furyl [3,2-c] quinoline derivatives |
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| Publication Number | Publication Date |
|---|---|
| CN1837208A CN1837208A (en) | 2006-09-27 |
| CN100376582C true CN100376582C (en) | 2008-03-26 |
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|---|---|---|---|
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1302804A (en) * | 1999-11-24 | 2001-07-11 | 阿迪尔公司 | Dihydrofuro [3,4-b] quinoline-1-ketone type compound, its preparation method and medicinal composition containing these compounds |
| CN1378535A (en) * | 1999-10-14 | 2002-11-06 | 科研制药株式会社 | Tetrahydroquinoline derivatives |
| JP2002322181A (en) * | 2001-04-23 | 2002-11-08 | Sankyo Co Ltd | Production method for quinoline derivative |
| US6656949B1 (en) * | 2002-09-12 | 2003-12-02 | Kaohsiung Medical University | 4-anilinofuro [3,2-c] quinoline derivatives, and preparation processes and uses of the same |
| CN1681823A (en) * | 2002-07-26 | 2005-10-12 | 武田药品工业株式会社 | Furoisoquinoline derivative and its application |
| CN1723210A (en) * | 2003-01-09 | 2006-01-18 | 田边制药株式会社 | Fused furan compound |
-
2006
- 2006-04-26 CN CNB2006100505213A patent/CN100376582C/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1378535A (en) * | 1999-10-14 | 2002-11-06 | 科研制药株式会社 | Tetrahydroquinoline derivatives |
| CN1302804A (en) * | 1999-11-24 | 2001-07-11 | 阿迪尔公司 | Dihydrofuro [3,4-b] quinoline-1-ketone type compound, its preparation method and medicinal composition containing these compounds |
| JP2002322181A (en) * | 2001-04-23 | 2002-11-08 | Sankyo Co Ltd | Production method for quinoline derivative |
| CN1681823A (en) * | 2002-07-26 | 2005-10-12 | 武田药品工业株式会社 | Furoisoquinoline derivative and its application |
| US6656949B1 (en) * | 2002-09-12 | 2003-12-02 | Kaohsiung Medical University | 4-anilinofuro [3,2-c] quinoline derivatives, and preparation processes and uses of the same |
| CN1723210A (en) * | 2003-01-09 | 2006-01-18 | 田边制药株式会社 | Fused furan compound |
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| Publication number | Publication date |
|---|---|
| CN1837208A (en) | 2006-09-27 |
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