CN106554299A - A kind of method of coproduction 3- methylindole and indole - Google Patents
A kind of method of coproduction 3- methylindole and indole Download PDFInfo
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- CN106554299A CN106554299A CN201510629976.XA CN201510629976A CN106554299A CN 106554299 A CN106554299 A CN 106554299A CN 201510629976 A CN201510629976 A CN 201510629976A CN 106554299 A CN106554299 A CN 106554299A
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- methylindole
- indole
- coproduction
- ethylene glycol
- aniline
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- 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
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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Abstract
The present invention relates to a kind of prepare indole for raw material by aniline and ethylene glycol, 1,2-PD while the process of coproduction 3- methylindole, mainly solve the problems, such as in prior art that indole production yield is low, product is single.The present invention carries out flow-type gas-solid-phase catalytic reaction in fixed bed reactors with Ag Quito phase catalyst, aniline and ethylene glycol, 1,2- Propylene Glycol is mixed in proportion continuous feed and enters fixed bed reactors, in a hydrogen atmosphere, heterogeneous catalytic reaction is carried out on solid catalyst bed, one-step synthesis indole simultaneously coproduction 3- methylindole, indole yield reach 84%（In terms of ethylene glycol）, 3- methylindole yields reach 43%（In terms of 1,2- Propylene Glycol）.The catalytic process not only has the advantages that greater activity, selectivity and stability, but also the characteristics of there is a step to produce multiple products, process is simple, continuous operation, with low cost and environmental friendliness etc..
Description
Technical field
The present invention relates to a kind of method of coproduction 3- methylindole and indole, the method for specifically catalyzing and synthesizing 3- methylindole and indole by aniline and 1,2-PD, one step of ethylene glycol.
Background technology
Indole is the important source material for preparing medicine, pesticide, spice, dyestuff and feed additive, is important heterocycle fine-chemical intermediate.What the eighties was Japanese crosses the method that the aniline and ethylene glycol vapor- phase synthesis indole product in the presence of metallic catalyst has been invented on side et al..Course of reaction is as shown in Equation 1.
With aniline as catalytic material One Step Synthesis of Indole, not only low in raw material price, low production cost, and operating procedure are simple for the method, and environmental friendliness, with clear advantage, is a kind of most promising method of synthesis of indole.Matsuda etc. has found that the reactions of the catalyst to aniline and ethylene glycol One Step Synthesis of Indole such as Cd, Cu, Ag and Zn all have certain activity（USP4436917）.Under 350 DEG C, normal pressure, in fixed bed reaction, the yield of indole is all more than 20%.The indole yield of wherein Ag/SiO2-ZnO catalyst reaches more than 40%.The country has been also carried out this research.Document report（Catalysis journal.2003.v24(6),471-474）Infusion process have developed Ag/SiO2And Cu/SiO2Catalyst, and investigated aniline, the catalytic performance of ethylene glycol One Step Synthesis of Indole.The indole yield of two kinds of catalyst can reach 80% or so.
3- methylindole is important medicine, pesticide reagent, because of its exclusive chemical constitution so that its medicine for deriving and pesticide have unique physiologically active.3- methylindole synthetic methods are more at present, and Gopal and Siwach et al. mol ratio is 1:6 indole is raw material gas phase catalytic reaction with methanol, obtains the 3- methylindole that yield is 33%～55%（Appl Catal A:
General 2002 Vol.224 No.121-128）；With lutecium iridium complex as catalyst, in 111 DEG C of 20 h of back flow reaction, it is 73% that oxidative cyclization amino alcohol obtains the yield of 3- methylindole to Fujita et al.（Organic
Letters 2002 Nol.16 No.2691-2694）；Chan et al. is raw material in catalyst RuCl with aniline and methyl oxirane3In the presence of be cyclized into 3- methylindole and 2 methyl indole, wherein 3- methylindole yield only has 11%, and resulting product is mainly 2 methyl indole（Tetrahedron
Letters 2003 Vol.44 No.2975-2977）；Fischer sloughs hydrone with propionic aldehyde and phenylhydrazine heating and forms propionic aldehyde phenylhydrazone, then heats with sulphuric acid, sloughs amino molecule cyclisation and obtains 3- methylindole, yield 85%, but product separation is difficult（Org. Prep.
Proc. Int. 1993 Vol.25 No.607-610）；Yokoyama et al. uses palladium chtalyst 2- Iodoanilines and 1-propenol-3 to react, 3- methylindole yield 63%, post separation product（Adv. Synth.
Catal. 2007 Vol.349 No.662-668）；Simoneau et al. is reacted with phenylhydrazine and nitropropane, 3- methylindole yield 50%（Tetrahedron
Letters 2007 Vol.48 No.1809-1811）；Liu et al. is reported using KOH in THF and H2In O solvents, cetyl trimethyl ammonium is used（CTAB）Catalysis N- tolyl sulfur indole sloughs N- tosyls synthesis 3- methylindole（ORG PROCESS
RES DEV. 2008 Vol.12 No.778-780）.Liquid phase method prepares 3- methylindole, although having the advantages that compared with high product yield, but there is also considerable shortcoming, such as reaction raw materials are complicated, expensive, need using a large amount of toxic solvents pollution environment etc. in reaction condition more harsh, the dangerous property of operation and reaction.
Aniline and 1,2-PD single step reaction can generate 3- methylindole, and course of reaction is as shown in Equation 2.
The method not only low in raw material price, low production cost, operating procedure are simple, and cause the garbage of environmental pollution few in course of reaction, with clear advantage, are a kind of most promising methods of synthesis 3- methylindole.Campanati et al. is with mol ratio as 1:1 aniline and 1,2- Propylene Glycol are raw material, ZrO2/SiO2For catalyst, at 310 DEG C, 12% 3- methylindole is obtained by atmospheric fixed bed gas phase catalytic reaction 1h（Journal of
Catalysis 2005 Vol.232 No. 1-9）；Zheng et al. passes through aniline and 1,2- Propylene Glycol is raw material, Ag/SiO2For catalyst, atmospheric fixed bed gas phase catalytic synthesis 3- methylindole, yield is 35%（Chin. J.
Catal. 2008 Vol.29 No.1199-1201）.Above-mentioned test yield is low.
A kind of method that prior art there is no coproduction 3- methylindole and indole under catalyst action, and the technology of production indole has that indole yield is low, and the present invention targetedly solves the problem.
The content of the invention
The technical problem to be solved is the problem that indole yield is low present in prior art, product structure is single, there is provided a kind of method of new coproduction 3- methylindole and indole.The method is used in the production of indole and 3- methylindole, has the advantages that a step produces multiple products, high income, process is simple, continuous operation.
The technical solution used in the present invention is as follows：A kind of method of coproduction 3- methylindole and indole, it is characterised in that aniline is mixed in proportion with 1,2-PD, ethylene glycol and enters reaction zone, aniline inlet amount is respectively 5 with 1,2-PD, the mol ratio of ethylene glycol inlet amount:1~15:1、2:1~15:1, contact with catalyst, 200 ~ 500 DEG C of reaction temperature, 0 ~ 2Mpa of pressure, 0.2 ~ 20 second gas phase time of staying, generation includes indole, the product of 3- methylindole.Wherein, the conversion ratio of ethylene glycol and 1,2-PD is both greater than 98%.
In above-mentioned technical proposal, the reaction zone is fixed bed reactors.
The catalyst is Ag base catalyst, and the load quality percent of Ag is 1 ~ 40%, and carrier is SiO2。
The reaction zone preferable reaction temperature is 250 ~ 450 DEG C, and reaction pressure is calculated as 0 ~ 1.0MPa with gauge pressure, and the gas phase time of staying is 0.5 ~ 10 second.
Add the hydrogen that volume fraction is for 0.1 ~ 5% in the gas-phase feed, the addition volume fraction of water vapour is 0.5 ~ 50%.
Ag bases catalyst of the present invention is prepared using conventional infusion process, selects commercially available carrier.Using front needing hydrogen mixed gas to reduce, 5 ~ 100%, gaseous mixture volume space velocity is 100 ~ 1000h to general hydrogen volume content to catalyst-1, reduction temperature is 100 ~ 450 DEG C, and the recovery time is 1 ~ 72 hour.
In the charging of fixed bed reaction area, the water vapour of general addition volume fraction 0.5 ~ 50%, to delay the inactivation of catalyst, improves the yield of purpose product indole and 3- methylindole.After catalyst is inactivated, after cutting out raw material, be passed through nitrogen purging displacement it is clean after, be passed through containing volume fraction be 0.1 ~ 10 ~ oxygen and nitrogen blender carry out catalyst regeneration, after the completion of regeneration, be continuing with after being reduced.
In the reaction region aniline and ethylene glycol, 1,2- Propylene Glycol is converted into indole and 3- methylindole, aniline is typically in excessive state in the reaction region, ethylene glycol and 1,2-PD conversion ratio are very high, both can reach more than 98% conversion ratio, two major products are generated under same catalyst action, product structure diversification, reduces the cost of production, while reducing the circulating load of aniline.
The conversion ratio of the inventive method, 1,2-PD and ethylene glycol is more than 98%, and indole yield is 85%（Based on ethylene glycol）, 3- methylindole yield is 45%（Based on 1,2- Propylene Glycol）, achieve preferable technique effect.
The catalytic process of the inventive method not only has the advantages that greater activity, selectivity and stability, but also the characteristics of there is a step to produce multiple products, process is simple, continuous operation, with low cost and environmental friendliness etc..
Specific embodiment
Below by embodiment, the present invention is further elaborated, but is not limited only to the present embodiment.
Embodiment
1
Aniline and ethylene glycol, 1,2- Propylene Glycol press 5:1:1 (mol ratio) ratio enters fixed bed reactors, and catalyst is Ag/SiO2, the load capacity of Ag is 0.5%, 250 DEG C of reaction temperature, reaction pressure normal pressure, 0.5 second gas phase reaction time of staying, in gas-phase feed, the volume fraction of hydrogen addition is 5%, and the addition volume fraction of steam is 0.5%, reacted gaseous phase materials are condensed into condenser, condensed fluid is collected, oil-water separation is carried out, oil phase is detected, ethylene glycol reforming rate 87%, indole yield 40%（In terms of hexylene glycol）；1,2-PD conversion ratio 88%, 3- methylindole yield 10%（In terms of 1,2- Propylene Glycol）.
Embodiment
2
Aniline and ethylene glycol, 1,2- Propylene Glycol press 7:1:1 (mol ratio) ratio enters fixed bed reactors, and catalyst is Ag/SiO2, the load capacity of Ag is 5%, 300 DEG C of reaction temperature, reaction pressure 0.1MPa, 5 seconds gas phase reaction time of staying, in gas-phase feed, the volume fraction of hydrogen addition is 5%, and the addition volume fraction of steam is 5%, reacted gaseous phase materials are condensed into condenser, condensed fluid is collected, oil-water separation is carried out, oil phase is detected, ethylene glycol reforming rate 95%, indole yield 72%（In terms of ethylene glycol）；1,2-PD conversion ratio 95%, 3- methylindole yield 16%（In terms of 1,2- Propylene Glycol）.
Embodiment
3
Aniline and ethylene glycol, 1,2- Propylene Glycol press 10:1:1 (mol ratio) ratio enters fixed bed reactors, and catalyst is Ag/SiO2, the load capacity of Ag is 8%, 350 DEG C of reaction temperature, reaction pressure 0.5MPa, 10 seconds gas phase reaction time of staying, in gas-phase feed, the volume fraction of hydrogen addition is 3%, and the addition volume fraction of steam is 15%, reacted gaseous phase materials are condensed into condenser, condensed fluid is collected, oil-water separation is carried out, oil phase is detected, ethylene glycol reforming rate 98%, indole yield 80%（In terms of ethylene glycol）；1,2-PD conversion ratio 98%, 3- methylindole yield 40%（In terms of 1,2- Propylene Glycol）.
Embodiment
4
Aniline and ethylene glycol, 1,2- Propylene Glycol press 15:1:1 (mol ratio) ratio enters fixed bed reactors, and catalyst is Ag/SiO2, the load capacity of Ag is 8%, 400 DEG C of reaction temperature, reaction pressure 1.0MPa, 10 seconds gas phase reaction time of staying, in gas-phase feed, the volume fraction of hydrogen addition is 5%, and the addition volume fraction of steam is 30%, reacted gaseous phase materials are condensed into condenser, condensed fluid is collected, oil-water separation is carried out, oil phase is detected, ethylene glycol reforming rate 98%, indole yield 76%（In terms of ethylene glycol）；1,2-PD conversion ratio 98%, 3- methylindole yield 35%（In terms of 1,2- Propylene Glycol）.
Embodiment
5
Aniline and ethylene glycol, 1,2- Propylene Glycol press 15:1:1 (mol ratio) ratio enters fixed bed reactors, and catalyst is Ag/SiO2, the load capacity of Ag is 10%, 325 DEG C of reaction temperature, reaction pressure 0.7MPa, 10 seconds gas phase reaction time of staying, in gas-phase feed, the volume fraction of hydrogen addition is 5%, and the addition volume fraction of steam is 5%, reacted gaseous phase materials are condensed into condenser, condensed fluid is collected, oil-water separation is carried out, oil phase is detected, ethylene glycol reforming rate 99%, indole yield 84%（In terms of ethylene glycol）；1,2-PD conversion ratio 98%, 3- methylindole yield 43%（In terms of 1,2- Propylene Glycol）.
Claims (7)
1. a kind of method of coproduction 3- methylindole and indole, it is characterised in that aniline is mixed in proportion with 1,2-PD, ethylene glycol and enters reaction zone, aniline inlet amount is respectively 5 with 1,2-PD, the mol ratio of ethylene glycol inlet amount:1~15:1、2:1~15:1, contact with catalyst, 200 ~ 500 DEG C of reaction temperature, 0 ~ 2Mpa of pressure, 0.2 ~ 20 second gas phase time of staying, generation includes indole, the product of 3- methylindole.
2. the method for coproduction 3- methylindole and indole according to claim 1, it is characterised in that the reaction zone is fixed bed reactors.
3. the method for coproduction 3- methylindole and indole according to claim 1, it is characterised in that the catalyst is Ag base catalyst, and the load quality percent of Ag is 1 ~ 40%, and carrier is SiO2。
4. the method for coproduction 3- methylindole and indole according to claim 1, it is characterised in that 250 ~ 450 DEG C of the reaction temperature.
5. the method for coproduction 3- methylindole and indole according to claim 1, it is characterised in that the reaction pressure 0 ~ 1MPa in terms of gauge pressure.
6. the method for coproduction 3- methylindole and indole according to claim 1, it is characterised in that 0.5 ~ 10 second gas phase time of staying.
7. the method for coproduction 3- methylindole and indole according to claim 1, it is characterised in that add the hydrogen that volume fraction is for 0.1 ~ 5% in the reaction zone gas-phase feed, meanwhile, add the water vapour of volume fraction 0.5 ~ 50% in the gas-phase feed of reaction zone.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106938973A (en) * | 2017-03-28 | 2017-07-11 | 青岛科技大学 | A kind of method of single column heterogeneous azeotropic rectification separation aniline and ethylene glycol azeotropic mixture |
| CN107892667A (en) * | 2017-11-03 | 2018-04-10 | 苏州艾缇克药物化学有限公司 | A kind of preparation method of 3 methyl indol |
| CN112279799A (en) * | 2019-07-26 | 2021-01-29 | 中石化南京化工研究院有限公司 | Method for preparing spice-grade indole by extraction crystallization |
-
2015
- 2015-09-29 CN CN201510629976.XA patent/CN106554299A/en active Pending
Non-Patent Citations (3)
| Title |
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| 石雷等: "预处理条件对一步法合成吲哚用Ag/SiO2催化剂活性的影响", 《催化学报》 * |
| 郑佳聪等: "Ag/SiO2催化剂上气相合成3-甲基吲哚", 《催化学报》 * |
| 高宁等: "一步法合成吲哚的Ag/SiO2催化剂", 《化学工业与工程》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106938973A (en) * | 2017-03-28 | 2017-07-11 | 青岛科技大学 | A kind of method of single column heterogeneous azeotropic rectification separation aniline and ethylene glycol azeotropic mixture |
| CN107892667A (en) * | 2017-11-03 | 2018-04-10 | 苏州艾缇克药物化学有限公司 | A kind of preparation method of 3 methyl indol |
| CN112279799A (en) * | 2019-07-26 | 2021-01-29 | 中石化南京化工研究院有限公司 | Method for preparing spice-grade indole by extraction crystallization |
| CN112279799B (en) * | 2019-07-26 | 2022-02-22 | 中石化南京化工研究院有限公司 | Method for preparing spice-grade indole by extraction crystallization |
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