GB2399816A - A catalyst/reagent composition comprising a poly-amino acid catalyst and an epoxidation reagent and its use in asymmetric epoxidation reactions - Google Patents
A catalyst/reagent composition comprising a poly-amino acid catalyst and an epoxidation reagent and its use in asymmetric epoxidation reactions Download PDFInfo
- Publication number
- GB2399816A GB2399816A GB0306931A GB0306931A GB2399816A GB 2399816 A GB2399816 A GB 2399816A GB 0306931 A GB0306931 A GB 0306931A GB 0306931 A GB0306931 A GB 0306931A GB 2399816 A GB2399816 A GB 2399816A
- Authority
- GB
- United Kingdom
- Prior art keywords
- catalyst
- epoxidation
- reagent
- poly
- aqueous phase
- 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.)
- Granted
Links
- 238000006735 epoxidation reaction Methods 0.000 title claims abstract description 31
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 30
- 239000003054 catalyst Substances 0.000 title claims abstract description 24
- 239000000203 mixture Substances 0.000 title claims abstract description 22
- 150000001413 amino acids Chemical class 0.000 title claims abstract 11
- 239000003377 acid catalyst Substances 0.000 title claims abstract 6
- 238000000034 method Methods 0.000 claims abstract description 18
- 239000008346 aqueous phase Substances 0.000 claims abstract description 14
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 8
- -1 sulfonyl compound Chemical class 0.000 claims abstract description 7
- 150000002118 epoxides Chemical class 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 108010050934 polyleucine Proteins 0.000 claims abstract description 4
- 108010054442 polyalanine Proteins 0.000 claims abstract description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims description 2
- 229940024606 amino acid Drugs 0.000 claims 6
- 239000000758 substrate Substances 0.000 claims 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- 239000002904 solvent Substances 0.000 claims 2
- 229930182819 D-leucine Natural products 0.000 claims 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 1
- 239000007800 oxidant agent Substances 0.000 claims 1
- 150000002978 peroxides Chemical group 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 abstract 1
- 125000002081 peroxide group Chemical group 0.000 abstract 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N epoxyketone group Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D301/00—Preparation of oxiranes
- C07D301/02—Synthesis of the oxirane ring
- C07D301/03—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds
- C07D301/12—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with hydrogen peroxide or inorganic peroxides or peracids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/32—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/34—Compounds containing oxirane rings with hydrocarbon radicals, substituted by sulphur, selenium or tellurium atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/38—Compounds containing oxirane rings with hydrocarbon 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
- C07D303/40—Compounds containing oxirane rings with hydrocarbon 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 by ester radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Epoxy Compounds (AREA)
Abstract
A process for the asymmetric epoxidation of a , b -unsaturated carbonyl or sulfonyl compounds comprises providing, in the absence of an aqueous phase, a catalyst/reagent composition comprising a poly-amino acid catalyst which encapsulates an epoxidation reagent, contacting the catalyst/reagent compsition with an a , b -unsaturated carbonyl or sulfonyl compound under conditions effective to provide at least partial asymmetric epoxidation and recovering the resulting asymmetric epoxide. The catalyst is preferably polyleucine, polyalanine or polyneopentylglycine and the epoxidation reagent is preferably a peroxide, perchlorate or perborate. Catalyst/reagent compositions for use in epoxidation reactions comprise, in the absence of an aqueous phase, a poly-amino acid encapsulating an epoxidation reagent and/or comprise the formula (Leu)n(H2O2)xn(H2O)yn where x is preferably 2-300 and y is 1-1000. A process for preparing such catalyst/reagent compositions comprises contacting the poly-amino acid with an aqueous phase comprising the epoxidation agent under conditions to cause the epoxidation reagent to be encapsulated by the poly-amino acid and then separating the resulting catalyst/reagent composition from the aqueous phase. The aqueous phase may comprise the epoxidation reagent in the presence of a phase transfer catalyst.
Description
DESCRIPTION
PROCESS FOR THE PRODUCTION OF ASYMMETRIC EPOXIDES AND
CATALYTIC COMPOSITION FOR USE THEREIN
This invention relates a process for the production of asymmetric epoxides and to a catalytic composition for use therein. The process of the invention is especially applicable to chemical reactions involving the asymmetric epoxidation of a,,8- unsaturated carbonyl or sulphonyl compounds, such as oe,'-unsaturated ketones, esters and ketoesters.
The transformation of a,,8-unsaturated ketones to epoxy ketones using hydrogen peroxide as the epoxidation reagent is known as the WeitzScheffer reaction. This reaction has been the subject of considerable interest due to the asymmetric variants that can be produced from the reaction. The functional applications of epoxy ketones are diverse but include use in the manufacture of pharmaceutical intermediates generally, and the so-called Statin drug intermediates in particular.
Julia and Colonna developed the use of polyalanine or polyleucine as a catalyst for epoxidation of a,,8-unsaturated ketones, the conditions for the epoxidation reaction consisting of aqueous hydrogen peroxide containing sodium hydroxide, a water immiscible organic solvent such as hexane or toluene and an insoluble poly (amino acid) catalyst (Band, S. et aL, (1984) Tetrahedron 40, 5207). The reaction mixture is triphasic, comprising an aqueous phase, an organic phase and an insoluble polyamino acid phase. One problem with this procedure is that the catalyst forms a viscous paste that greatly reduces the filtering speed and makes it difficult to recover the catalyst after the reaction. Such reduction in filtration speed makes the procedure
Claims (15)
1. A process for the asymmetric epoxidation of a,,B-unsaturated carbonyl or sulphonyl compounds comprising: providing, in the absence of an aqueous phase, a catalyst/reagent composition comprising a poly-amino acid catalyst effective for catalysing the asymmetric epoxidation reaction, the poly-amino acid catalyst encapsulating an epoxidation reagent effective for epoxidation of a,3-unsaturated carbonyl or sulphonyl compounds; contacting the catalyst/reagent composition with an,- unsaturated carbonyl or sulphonyl compound substrate under conditions effective to provide at least partial asymmetric epoxidation of the substrate by the epoxidation reagent, and recovering the resulting asymmetric epoxide.
2. A process accordlug to claim 1 wherein the catalyst is selected from the following group: polyleucine. polyalanine and polyneopentylglycine.
3. A process according to claim 2 wherein the catalyst is poly-(L-leucine) or poly-(D-leucine).
4. A process according to any one of claims I to 3 wherein the epoxidation reagent is selected from peroxides, perchlorates, and perforates.
5. A process according to claim 4 wherein the epoxidation reagent is hydrogen peroxide.
6. A process according to any one of claims I to 5 wherein the epoxidation reaction proceeds in the presence of an organic solvent.
7. A process according to claim 6 wherein the solvent is selected from toluene, dichloromethane, hexane and tetrabydrofuran. - 17
8. A process according to any one of claims l to 7 providing a desired asymmetric epoxide product in significant enantiomeric excess with respect to its enantiomer, for example an enantiomeric excess of at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% or more.
9. A catalyst/reagent composition for use in epoxidation reactions comprising, in the absence of an aqueous phase, a poly-amino acid encapsulating an epoxidation reagent.
10. A catalystlreagent composition for use in epoxidation reactions comprising the following formula, (Leu)n (H2O2)xn (H2O)yn.
I 1. A catalyst/reagent composition for use in epoxidation reactions as described in claim 10, wherein x is in the range of 2-300 and y is in the range of 1- 1 000.
12. Use of a catalystlreagent composition according to any one of claims 9 to 11 in a process according to any one of claims 1 to 11.
13. A process for preparing a catalystlreagent composition according to any one of claims 9 to 11 comprising contacting the poly-amino acid with an aqueous phase comprising the epexidation reagent under conditions effective to cause the epoxidation reagent to be encapsulated by the polyamino acid, and subsequently separating the resulting catalyst reagent composition from the aqueous phase.
14. A process according to claim 13 comprising mixing the poly-amino acid catalyst with an aqueous phase comprising the epoxidation reagent in the presence of a phase transfer catalyst, and subsequently removing the aqueous phase. - 18
15. A process for the asymmetric epoxidation of a,-unsaturated carbonyl or sulphonyl compounds, the process comprising the steps of: forming a catalyst reagent pre-mixture comprising: an aqueous phase containing an oxidising agent, an insoluble phase containing a poly-amino acid catalyst and an organic phase containing a solvent; removing the aqueous phase from the mixture to form a catalyst reagent composition; contacting the catalyst reagent composition with an a,,B-unstaurated carbonyl or sulphonyl compound substrate; incubating the substrate in the catalyst reagent composition; recovering an asymmetric epoxide from the catalyst mixture; and optionally using the catalyst mixture again for further epexidation reactions.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0306931A GB2399816B (en) | 2003-03-26 | 2003-03-26 | Process for the production of asymmetric epoxides and catalytic composition for use therein |
| PCT/GB2004/001277 WO2004085415A1 (en) | 2003-03-26 | 2004-03-25 | Process for the production of asymmetric epoxides under non-aqueous conditions and catalytic composition for use therein |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0306931A GB2399816B (en) | 2003-03-26 | 2003-03-26 | Process for the production of asymmetric epoxides and catalytic composition for use therein |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB0306931D0 GB0306931D0 (en) | 2003-04-30 |
| GB2399816A true GB2399816A (en) | 2004-09-29 |
| GB2399816B GB2399816B (en) | 2006-06-07 |
Family
ID=9955548
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0306931A Expired - Fee Related GB2399816B (en) | 2003-03-26 | 2003-03-26 | Process for the production of asymmetric epoxides and catalytic composition for use therein |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB2399816B (en) |
| WO (1) | WO2004085415A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013012998A1 (en) * | 2011-07-19 | 2013-01-24 | Emory University | Tak1 kinase inhibitors, compositions, and used related thereto |
-
2003
- 2003-03-26 GB GB0306931A patent/GB2399816B/en not_active Expired - Fee Related
-
2004
- 2004-03-25 WO PCT/GB2004/001277 patent/WO2004085415A1/en not_active Ceased
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013012998A1 (en) * | 2011-07-19 | 2013-01-24 | Emory University | Tak1 kinase inhibitors, compositions, and used related thereto |
Also Published As
| Publication number | Publication date |
|---|---|
| GB2399816B (en) | 2006-06-07 |
| GB0306931D0 (en) | 2003-04-30 |
| WO2004085415A1 (en) | 2004-10-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 732E | Amendments to the register in respect of changes of name or changes affecting rights (sect. 32/1977) | ||
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 20070326 |