NO179866B - Process for the preparation of indoles - Google Patents
Process for the preparation of indoles Download PDFInfo
- Publication number
- NO179866B NO179866B NO942381A NO942381A NO179866B NO 179866 B NO179866 B NO 179866B NO 942381 A NO942381 A NO 942381A NO 942381 A NO942381 A NO 942381A NO 179866 B NO179866 B NO 179866B
- Authority
- NO
- Norway
- Prior art keywords
- indoles
- formic acid
- hours
- preparation
- indole
- Prior art date
Links
- 150000002475 indoles Chemical class 0.000 title claims abstract description 7
- 238000000034 method Methods 0.000 title claims abstract description 5
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 18
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 9
- 235000019253 formic acid Nutrition 0.000 claims abstract description 9
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000006114 decarboxylation reaction Methods 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- CIYTWRCWBDXUQU-UHFFFAOYSA-N 4-(5-methoxy-1h-indol-3-yl)butanoic acid Chemical compound COC1=CC=C2NC=C(CCCC(O)=O)C2=C1 CIYTWRCWBDXUQU-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- -1 acetic acid Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- HGEYJZMMUGWEOT-UHFFFAOYSA-N roxindole Chemical compound C12=CC(O)=CC=C2NC=C1CCCCN(CC=1)CCC=1C1=CC=CC=C1 HGEYJZMMUGWEOT-UHFFFAOYSA-N 0.000 description 1
- 229950000366 roxindole Drugs 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Oppfinnelsen vedrrer en ny fremgangsmåte for fremstilling av indoler ved dekarboksylering av tilsvarende indol-2-karboksylsyrer, kj ennetegnet ved at disse behandles med maursyre.The invention relates to a new process for the preparation of indoles by decarboxylation of corresponding indole-2-carboxylic acids, characterized in that these are treated with formic acid.
Description
Oppfinnelsen vedrører en ny fremgangsmåte for fremstilling av indoler ved dekarboksylering av tilsvarende indol-2-karboksylsyrer. The invention relates to a new method for producing indoles by decarboxylation of corresponding indole-2-carboxylic acids.
Indol-2-karboksylsyrer dekarboksyleres vanligvis ved at en oppløsning derav i et høytkokende tertiært amin varmes opp inntil tilbakeløp (jf. f.eks. Houben-Weyl/Muller, Methoden der organischen Chemie; 1952, bind 8, s. 486). Indole-2-carboxylic acids are usually decarboxylated by heating a solution thereof in a high-boiling tertiary amine to reflux (cf. e.g. Houben-Weyl/Muller, Methoden der organischen Chemie; 1952, vol. 8, p. 486).
Således ble 4-(5-metoksy-3-indolyl)-smørsyren (I), et mellomprodukt for syntesen av roksindol, tidligere fremstilt ved 24-timers oppvarming av en oppløsning av 3-(3-karboksy-propyl)-5-metoksyindol-2-karboksylsyre (II) i N,N-dimetyl-anilin eller N,N-dietylanilin til 190°C. Thus, 4-(5-methoxy-3-indolyl)-butyric acid (I), an intermediate for the synthesis of roxindole, was previously prepared by heating a solution of 3-(3-carboxy-propyl)-5-methoxyindole for 24 hours -2-carboxylic acid (II) in N,N-dimethylaniline or N,N-diethylaniline to 190°C.
Det er da uheldig med den høye reaksjonstemperaturen som bringer med seg apparaturproblemer og bare tillater en produksjon i små anlegg, samt den lange reaksjonsvarighet og dermed et høyt energiforbruk. It is then unfortunate that the high reaction temperature brings with it equipment problems and only allows production in small plants, as well as the long reaction duration and thus a high energy consumption.
Til grunn for oppfinnelsen lå den oppgave å finne frem til en ny fremstillingsfremgangsmåte for indoler, særlig I som ikke, eller bare i lite omfang, oppviser den nevnte ulempe. The invention was based on the task of finding a new production method for indoles, especially I which does not, or only to a small extent, exhibit the aforementioned disadvantage.
Det ble funnet at man ved oppvarming av en oppløsning av II i maursyre får I i høyere utbytte. Det er for såvidt overraskende etter som indoler generelt anses for å være svært labil overfor syrer. Dette viste seg også ved forsøk på å erstatte maursyre med andre syrer, som eddiksyre, fortynnet vandig svovelsyre eller fortynnet vandig saltsyre. Det skjedde enten slett ingen omsetning eller I oppstod bare i lavt utbytte under dannelse av biprodukter. It was found that by heating a solution of II in formic acid, I is obtained in higher yield. This is somewhat surprising as indoles are generally considered to be very labile towards acids. This was also shown by attempts to replace formic acid with other acids, such as acetic acid, dilute aqueous sulfuric acid or dilute aqueous hydrochloric acid. There was either no turnover at all or I only occurred in low yield during the formation of by-products.
Fremgangsmåten lar seg overføre til andre indol-2-karboksylsyrer med godt resultat. The method can be transferred to other indole-2-carboxylic acids with good results.
Gjenstand for oppfinnelsen er en fremgangsmåte for fremstilling av indoler ved dekarboksylering av tilsvarende indol-2-karboksylsyrer, kjennetegnet ved at man behandler disse med maursyre. The subject of the invention is a method for producing indoles by decarboxylation of corresponding indole-2-carboxylic acids, characterized by treating these with formic acid.
Ved denne fremgangsmåten anvender man maursyre som hensiktsmessig kan inneholde ca. 0-50 % vann. Reaksjons-temperaturene ligger mellom 20 og 107°C, fortrinnsvis mellom 80 og 107°C. Ved de høyere temperaturer bruker man reaksjons-tider mellom ca. 1 og 10 timer, fortrinnsvis mellom 2 og 4 timer, ved de lavere temperaturer tilsvarende lengre tider. In this method, formic acid is used, which can appropriately contain approx. 0-50% water. The reaction temperatures are between 20 and 107°C, preferably between 80 and 107°C. At the higher temperatures, reaction times between approx. 1 and 10 hours, preferably between 2 and 4 hours, at the lower temperatures corresponding to longer times.
Ved de nedenfor angitte prosentangivelser dreier det seg om volumprosenter. The percentages stated below refer to volume percentages.
Eksempel 1 Example 1
En blanding av 14,2 g II og 120 g 77,4 %-ig maursyre ble kokt i 3 timer og så inndampet under redusert trykk. Det ble tilsatt fortynnet natronlut, klaret kortvarig med aktivt karbon ved 40°C og utfelt med saltsyre inntil pH 1,5. Det ut-felte I ble frafiltrert, vasket med vann og tørket under redusert trykk ved 50°C. Utbytte: 10,9 g. A mixture of 14.2 g of II and 120 g of 77.4% formic acid was boiled for 3 hours and then evaporated under reduced pressure. Diluted caustic soda was added, clarified briefly with activated carbon at 40°C and precipitated with hydrochloric acid until pH 1.5. The precipitated I was filtered off, washed with water and dried under reduced pressure at 50°C. Yield: 10.9 g.
Eksempel 2 Example 2
Det ble arbeidet som angitt i eksempel 1, men med 100 %-ig maursyre og benyttet en reaksjonstid på 2 timer. The work was carried out as indicated in example 1, but with 100% formic acid and a reaction time of 2 hours was used.
Eksempel 3 Example 3
Det ble arbeidet som angitt i eksempel 1, men med 50 %-ig maursyre. Reaksjonstid: 5 timer. The work was carried out as indicated in example 1, but with 50% formic acid. Reaction time: 5 hours.
Eksempel 4 Example 4
Det ble arbeidet som angitt i eksempel 1, men ved 80°C. Reaksjonstid: 30 timer. The work was carried out as indicated in example 1, but at 80°C. Reaction time: 30 hours.
Eksempel 5 Example 5
Analogt med eksempel 1 fikk man indol fra indol-2-karboksylsyre. Analogous to example 1, indole was obtained from indole-2-carboxylic acid.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4320835A DE4320835C1 (en) | 1993-06-23 | 1993-06-23 | Process for the preparation of indoles |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO942381D0 NO942381D0 (en) | 1994-06-22 |
| NO942381L NO942381L (en) | 1994-12-27 |
| NO179866B true NO179866B (en) | 1996-09-23 |
| NO179866C NO179866C (en) | 1997-01-02 |
Family
ID=6491009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO942381A NO179866C (en) | 1993-06-23 | 1994-06-22 | Process for the preparation of indoles |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0632024A1 (en) |
| JP (1) | JPH0710837A (en) |
| KR (1) | KR950000666A (en) |
| CN (1) | CN1102409A (en) |
| AU (1) | AU6479794A (en) |
| CA (1) | CA2126416A1 (en) |
| CZ (1) | CZ154594A3 (en) |
| DE (1) | DE4320835C1 (en) |
| HU (1) | HUT75197A (en) |
| NO (1) | NO179866C (en) |
| PL (1) | PL303946A1 (en) |
| SK (1) | SK75394A3 (en) |
| TW (1) | TW267162B (en) |
| ZA (1) | ZA944487B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7206261B2 (en) | 2002-08-30 | 2007-04-17 | Ricoh Company, Ltd. | Loading mechanism, drive unit, and information processing apparatus for an information recording medium |
| DE202009015656U1 (en) | 2009-11-26 | 2010-03-18 | Sunpex Technology Co., Ltd. | Drive mechanism of an electric wheelchair |
| CN109694343B (en) * | 2018-12-19 | 2020-07-28 | 帕潘纳(北京)科技有限公司 | Decarboxylation method of heterocyclic carboxylic acid compounds |
-
1993
- 1993-06-23 DE DE4320835A patent/DE4320835C1/en not_active Expired - Fee Related
-
1994
- 1994-06-15 EP EP94109146A patent/EP0632024A1/en not_active Withdrawn
- 1994-06-17 AU AU64797/94A patent/AU6479794A/en not_active Abandoned
- 1994-06-20 CN CN94106708A patent/CN1102409A/en active Pending
- 1994-06-20 SK SK753-94A patent/SK75394A3/en unknown
- 1994-06-20 TW TW083105572A patent/TW267162B/zh active
- 1994-06-21 CA CA002126416A patent/CA2126416A1/en not_active Abandoned
- 1994-06-21 JP JP6138964A patent/JPH0710837A/en active Pending
- 1994-06-22 NO NO942381A patent/NO179866C/en unknown
- 1994-06-22 HU HU9401887A patent/HUT75197A/en unknown
- 1994-06-22 ZA ZA944487A patent/ZA944487B/en unknown
- 1994-06-22 KR KR1019940014145A patent/KR950000666A/en not_active Application Discontinuation
- 1994-06-22 CZ CZ941545A patent/CZ154594A3/en unknown
- 1994-06-22 PL PL94303946A patent/PL303946A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA944487B (en) | 1995-02-15 |
| NO942381L (en) | 1994-12-27 |
| NO942381D0 (en) | 1994-06-22 |
| PL303946A1 (en) | 1995-01-09 |
| NO179866C (en) | 1997-01-02 |
| AU6479794A (en) | 1995-01-05 |
| DE4320835C1 (en) | 1994-09-08 |
| KR950000666A (en) | 1995-01-03 |
| CZ154594A3 (en) | 1995-01-18 |
| EP0632024A1 (en) | 1995-01-04 |
| HUT75197A (en) | 1997-04-28 |
| JPH0710837A (en) | 1995-01-13 |
| CN1102409A (en) | 1995-05-10 |
| TW267162B (en) | 1996-01-01 |
| HU9401887D0 (en) | 1994-09-28 |
| CA2126416A1 (en) | 1994-12-24 |
| SK75394A3 (en) | 1995-03-08 |
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