EP1268403A1 - Verfahren zur beckmann-umlagerung organischer oxime - Google Patents
Verfahren zur beckmann-umlagerung organischer oximeInfo
- Publication number
- EP1268403A1 EP1268403A1 EP01936059A EP01936059A EP1268403A1 EP 1268403 A1 EP1268403 A1 EP 1268403A1 EP 01936059 A EP01936059 A EP 01936059A EP 01936059 A EP01936059 A EP 01936059A EP 1268403 A1 EP1268403 A1 EP 1268403A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- microreactor
- acid
- rearrangement
- mixture
- organic
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00873—Heat exchange
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/0095—Control aspects
- B01J2219/00984—Residence time
Definitions
- the present invention relates to a process for the Beckma ⁇ n rearrangement of organic oximes
- the object of the present invention is therefore to provide a process for the Beckmann rearrangement of organic oximes which avoids the disadvantages mentioned above.
- This process should in particular be able to be carried out in a simple, reproducible manner with increased safety for humans and the environment and with good yields, and the reaction conditions should be very easy to control
- the solution to this problem is surprisingly achieved by the inventive method for Beckman rearrangement of organic oximes in which the organic oxime in liquid or dissolved form is mixed with at least one rearrangement reagent in liquid or dissolved form in at least one microreactor during a residence time and the rearranged organic compound optionally isolated from the reaction mixture
- individual organic oximes or mixtures of at least two of these compounds can be reacted by the claimed process.
- a microreactor in the sense of the invention is a reactor with a volume ⁇ 1000 ⁇ i in which the liquids and / or solutions are intimately mixed at least once.
- the volume of the microreactor is preferably ⁇ 100 ⁇ l, particularly preferably ⁇ 50 ⁇ l
- the microreactor is preferably made from thin interconnected silicon structures
- the microreactor is preferably a miniaturized flow reactor, particularly preferably a static micromixer.
- the microreactor is particularly preferably a static micromixer as described in the patent application with the international publication number WO 96/30113, which is hereby introduced as a reference and is part of the disclosure
- Microreactor has small channels in which fluids and / or chemical solutions are present Compounds are mixed together by the kinetic energy of the flowing liquids and / or solutions.
- the channels of the microreactor preferably have a diameter of 10 to 1000 ⁇ m, particularly preferably 20 to 800 ⁇ m and very particularly preferably 30 to 400 ⁇ m.
- the liquids and / or solutions are preferably pumped into the microreactor in such a way that they flow through it at a flow rate of 0.01 ⁇ l / min to 100 ml / mm, particularly preferably 1 ⁇ l / min to 1 ml / min.
- the microreactor can preferably be tempered.
- the microreactor is preferably connected via an outlet to at least one reference section, preferably a capillary, particularly preferably a temperature-controlled capillary.
- the liquids and / or solutions are passed into this residence zone or capillary after their mixing in the microreactor to extend their residence time.
- the residence time in the sense of the invention is the time between the mixing of the starting materials and the working up of the resulting reaction solution for the analysis or isolation of the desired product (s).
- the required residence time in the process according to the invention depends on various parameters, such as, for example, the temperature or the reactivity of the starting materials. It is possible for the person skilled in the art to adapt the residence time to these parameters and thus to achieve an optimal reaction course
- the residence time of the reaction solution in the system used comprising at least one microreactor and possibly a residence section, can be set by selecting the flow rate of the liquids and / or solutions used.
- the reaction mixture is likewise preferably passed through two or more microreactors connected in series. The result of this is that the residence time is extended even at an increased flow rate and the components of the rearrangement reaction are reacted in such a way that an optimal product yield of the desired rearranged organic compound (s) is achieved.
- reaction mixture is passed through two or more microreactors arranged in parallel in order to increase the throughput.
- the number and the arrangement of the channels in one or more microreactor (s) are varied in such a way that the residence time is lengthened, so that here, too, with an increased flow rate an optimal yield of the desired rearranged one or more organic association (s) is achieved.
- the residence time of the reaction solution in the microreactor, if appropriate in the microreactor, and the reference distance are preferably ⁇ 15 hours, preferably ⁇ 3 hours, particularly preferably ⁇ 1 hour
- the method according to the invention can be carried out in a very wide temperature range, which is essentially due to the temperature resistance of the reference section, if necessary, for building the microreactor. and other components such as connections and - 0 -
- the process according to the invention is preferably carried out at a temperature of from -100 to +250 ° C., preferably from -78 to + 150 ° C., particularly preferably from 0 to +40 ° C.
- the method according to the invention can be carried out either continuously or batchwise. It is preferably carried out continuously.
- the course of the reaction of the Beckmann rearrangement in the method according to the invention can be followed and, if necessary, regulated using various analytical methods known to the person skilled in the art.
- the course of the reaction is preferably chromatographic, particularly preferably by
- the rearranged products are isolated, if appropriate.
- the rearranged product (s) is (are) isolated from the reaction mixture by extraction.
- organic oximes known to those skilled in the art as substrates of Beckmann rearrangements can be used as organic oximes in the process according to the invention.
- the organic oximes are preferred Oximes selected from aliphatic, aromatic or heteroaromatic ketoximes.
- aliphatic ketoximes known to the person skilled in the art which are suitable as a substrate for Beckmann rearrangements can be used as the aliphatic ketoxime.
- Straight-chain, branched, cyclic, saturated and unsaturated compounds are also included.
- Aromatic ketoxime used can be any aromatic ketoxime known to those skilled in the art, which can be used as a substrate for
- Beckmann rearrangements are suitable.
- this encompasses compounds and / or derivatives which comprise a monocyclic and / or polycyclic homoaromatic basic structure or a corresponding partial structure, e.g. in the form of substituents.
- heteroaromatic ketoximes known to the person skilled in the art which are suitable as a substrate for Beckmann rearrangements and which contain at least one heteroatom can be used as the heteroaromatic ketoxime.
- Heteroaromatic ketoximes for the purposes of the invention include heteroaromatic compounds and / or their derivatives which have at least one monocyclic and / or polycyclic heteroaromatic backbone or a corresponding partial structure, e.g. in the form of substituents, have heteroaromatic basic skeletons or partial structures particularly preferably comprise at least one oxygen, nitrogen and / or sulfur atom.
- Beckmann rearrangement reagents used in the process according to the invention are all rearrangement reagents known to the person skilled in the art that are suitable for Beckmann rearrangements, or a mixture of at least two / -
- the rearrangement reagent is at least one compound selected from acids, acid anhydrides, acid halides, carbodiimides, cyanoformates, Lewis acids or a mixture of these rearrangement reagents.
- the preferred acid used is p-totuoisulfonic acid, methanesulfonic acid, trifluoroacetic acid, sulfuric acid, hydrochloric acid, perchloric acid or a mixture of two or more of these acids.
- Preferred acid anhydrides are acetic anhydride, trifluoroacetic anhydride, trifluoromethanesulfonic acid hydride or a mixture thereof.
- ethyl cyanoformate is a preferred cyanoformate
- dicyciohexyicarbodiimide and / or carbonyldiimidazole are preferred carbodimides.
- Preferred Lewis acids also include aluminum compounds, preferably aluminum chloride, methyl aluminum dichloride, dimethyl aluminum chloride, diisobutyl aluminum hydride. Titanium compounds, preferably TiCl 4 , tin compounds, preferably SnCl 4 , zinc compounds, preferably ZnCl 2 , boron compounds, preferably BCI 3, or a mixture of at least two of the aforementioned compounds
- the molar ratio of organic oxime to the rearrangement reagent used in the process according to the invention depends on the reactivity of the organic oximes used and the
- Rearrangement reagents a Preferably, the rearrangement reagent u ⁇ d the organic oxime used in an aquimolar ratio.
- the rearrangement reagent is used in a 1.3-fold to 2-fold molar excess, particularly preferably in a 1.4-fold to 1.9-fold, very particularly preferably in a 1.5-fold to 1. ⁇ -fold excess, based on the organic oxime.
- the selectivity of the reaction itself depends on a number of other parameters, e.g. the concentration of the reagents used, e.g. the temperature, the type of rearrangement reagent used or the residence time. It is possible for the person skilled in the art to adapt the various parameters to the respective Beckmann rearrangement in such a way that the desired ( ⁇ ) rearranged product (s) is (are) obtained.
- organic oximes and rearrangement reagents used are either themselves liquid or are present in dissolved form. If these are not themselves already in liquid form, they must therefore be dissolved in a suitable solvent before the process according to the invention is carried out.
- Preferred solvents are hatogenated solvents, particularly preferably dichloromethane.
- paraffins particularly preferably pentane, hexane, heptane, octane, cyclopentane, cyclohepta ⁇ or
- the risk to humans and the environment from escaping chemicals is considerably reduced and thus leads to a increased safety when handling hazardous substances.
- the Beckmann rearrangement of organic oximes by the process according to the invention also enables better control of the reaction conditions, such as reaction time and reaction temperature, than is possible in the conventional processes.
- the risk of explosions in the case of very strongly exothermic Beckmann rearrangements is significantly reduced in the method according to the invention.
- the temperature can be individually selected and kept constant in each volume element of the system.
- the course of the reaction of the Beckmann rearrangement can be regulated very quickly and precisely in the method according to the invention.
- the rearranged organic products can be obtained in very good and reproducible yields.
- the Beckmann rearrangement of acetophenone oxime with methanesulfonylchloride was carried out in a static micromixer (Ilmenau University of Technology, Faculty of Mechanical Engineering, Dr -Ing. Norbert Schwesinger, PO Box 100565, D-98684 Ilmenau) with a size of 40 mm x 25 mm x 1 mm In total there were 11 mixing stages with a volume of 0, 125 ⁇ l each. The total pressure loss was approximately 1000 Pa
- the static micromixer was connected via an outlet and an Omnifit medium pressure HPLC connection component (Omnifit, Great Britain) to a Teflon capillary with an inner diameter of 0.49 mm and a length of 1.0 m.
- the reaction was carried out at 40 ° C, 50 ° C, 60 ° C and 70 ° C.
- the static micromixer and the Teflon capillary were tempered to the respective temperature in a thermostatted double-jacket vessel.
- a 2 ml disposable injection syringe was filled with part of a solution of 540 mg (4 mmol) of acetophenone oxime and 40 ml of Py ⁇ din and a further 2 ml syringe with part of a solution of 680 mg (6 mmol) of methanesulfonyl chloride in 40 ml of Py ⁇ din.
- the contents of both syringes were then transferred to the static micromixer using a metering pump (Harvard Apparatus Inc., Pump 22, South Natick, Massachussets, USA).
- the experimental set-up was calibrated before the reaction was carried out with regard to the dependence of the residence time on the pump flow rate.
- the residence time was set at 16 8, 4 and 2 minutes.
- the reactions were monitored using a Merck Hitachi LaChrom HPLC instrument. The ratio of starting material to product corresponding to the respective reaction conditions and residence time was also determined by means of HPLC on the above-mentioned instrument
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2000116106 DE10016106A1 (de) | 2000-03-31 | 2000-03-31 | Verfahren zur Beckmann-Umlagerung organischer Oxime |
DE10016106 | 2000-03-31 | ||
PCT/EP2001/002514 WO2001074758A1 (de) | 2000-03-31 | 2001-03-06 | Verfahren zur beckmann-umlagerung organischer oxime |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1268403A1 true EP1268403A1 (de) | 2003-01-02 |
Family
ID=7637157
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01936059A Withdrawn EP1268403A1 (de) | 2000-03-31 | 2001-03-06 | Verfahren zur beckmann-umlagerung organischer oxime |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1268403A1 (ja) |
JP (1) | JP2003529578A (ja) |
AU (1) | AU2001262082A1 (ja) |
DE (1) | DE10016106A1 (ja) |
WO (1) | WO2001074758A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008162935A (ja) * | 2006-12-28 | 2008-07-17 | Daicel Chem Ind Ltd | アミド又はラクタムの製造法 |
WO2009116537A1 (ja) * | 2008-03-17 | 2009-09-24 | 宇部興産株式会社 | ラウロラクタムの製造方法 |
FR2931478B1 (fr) * | 2008-05-26 | 2012-08-03 | Arkema France | Prodece de preparation de lactames comprenant une etape de photonitrosation suivie d'une etape de transposition de beckmann |
JP2009298706A (ja) * | 2008-06-11 | 2009-12-24 | Daicel Chem Ind Ltd | アミド又はラクタムの製造法 |
JP5572839B2 (ja) * | 2010-02-26 | 2014-08-20 | 国立大学法人山口大学 | アミド化合物の製造方法 |
CN113173829A (zh) * | 2021-04-19 | 2021-07-27 | 清华大学 | 一种酮肟贝克曼重排反应制备酰胺的催化方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2721199A (en) * | 1953-12-15 | 1955-10-18 | Du Pont | Production of amides or lactams from oximes |
DE19511603A1 (de) * | 1995-03-30 | 1996-10-02 | Norbert Dr Ing Schwesinger | Vorrichtung zum Mischen kleiner Flüssigkeitsmengen |
-
2000
- 2000-03-31 DE DE2000116106 patent/DE10016106A1/de not_active Withdrawn
-
2001
- 2001-03-06 JP JP2001572453A patent/JP2003529578A/ja active Pending
- 2001-03-06 AU AU2001262082A patent/AU2001262082A1/en not_active Abandoned
- 2001-03-06 EP EP01936059A patent/EP1268403A1/de not_active Withdrawn
- 2001-03-06 WO PCT/EP2001/002514 patent/WO2001074758A1/de active Application Filing
Non-Patent Citations (1)
Title |
---|
See references of WO0174758A1 * |
Also Published As
Publication number | Publication date |
---|---|
JP2003529578A (ja) | 2003-10-07 |
DE10016106A1 (de) | 2001-10-04 |
AU2001262082A1 (en) | 2001-10-15 |
WO2001074758A1 (de) | 2001-10-11 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
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17P | Request for examination filed |
Effective date: 20020821 |
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AK | Designated contracting states |
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AX | Request for extension of the european patent |
Free format text: AL;LT PAYMENT 20020821;LV PAYMENT 20020821;MK;RO PAYMENT 20020821;SI PAYMENT 20020821 |
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RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: WURZIGER, HANNS Inventor name: SCHWESINGER, NORBERT Inventor name: PIEPER, GUIDO |
|
17Q | First examination report despatched |
Effective date: 20050317 |
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STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
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18D | Application deemed to be withdrawn |
Effective date: 20100302 |