EP1368316A1 - Sels d'oxoammonium et leur utilisation - Google Patents

Sels d'oxoammonium et leur utilisation

Info

Publication number
EP1368316A1
EP1368316A1 EP02730001A EP02730001A EP1368316A1 EP 1368316 A1 EP1368316 A1 EP 1368316A1 EP 02730001 A EP02730001 A EP 02730001A EP 02730001 A EP02730001 A EP 02730001A EP 1368316 A1 EP1368316 A1 EP 1368316A1
Authority
EP
European Patent Office
Prior art keywords
oxoammonium
oxoammonium salt
salt according
group
alcohols
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Withdrawn
Application number
EP02730001A
Other languages
German (de)
English (en)
Inventor
Jörg Rademann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of EP1368316A1 publication Critical patent/EP1368316A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
    • C07D211/94—Oxygen atom, e.g. piperidine N-oxide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/30—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/50—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/11—Compounds covalently bound to a solid support

Definitions

  • the invention relates to new oxoammonium salts, their use and new oxidation processes.
  • oxoammonium salts are known as reactive intermediates in oxidations using the 2,2,6,6-tetramethylpiperidinoxyl radical (TEMPO), which is also described as polymer-bound (review: Arjan EJ de Nooy, Arie C. Besemer, Hermann van Bekkum, Synthesis 1996, 1153).
  • TEMPO 2,2,6,6-tetramethylpiperidinoxyl radical
  • the TEMPO is first converted into the corresponding oxoammonium salt by a cooxidant (e.g. NaOCI), which then oxidizes the substrate to be oxidized in the same reaction batch.
  • a cooxidant e.g. NaOCI
  • a disadvantage that arises from the use of this radical especially in the case of the desired oxidation of alcohols to aldehydes, is the overoxidation of aldehydes to carboxylic acids.
  • Another disadvantage that the use of TEMPO brings with it in oxidation reactions is the low reactivity towards non-benz
  • TEMPO precursor 1-hydroxy-4-oxo-2,2,6,6-tetramethylpiperidine which is bound to silica gel
  • this is first converted into TEMPO by a cooxidant, which then - presumably via an intermediate, non-isolated oxoammonium intermediate stage - oxidizes the substrate to be oxidized (Carsten Bolm, Thomas Fey, Chem. Commun., 1999, 1795-1796 ).
  • Alcohols are oxidized, but the yields, especially in the oxidation of secondary alcohols, leave something to be desired.
  • DMSO dimethyl sulfoxide
  • Periodinans and various heavy metal reagents the latter mostly based on either chromium or ruthenium oxides.
  • the object of the invention is therefore to provide new compounds which can be used as oxidizing agents and oxidation processes which overcome the disadvantages mentioned.
  • the oxoammonium salt according to the invention has a positively charged reactive section Z + , which has one of the following structures:
  • the counter ion which is denoted by X " , is an anion, in particular a halide ion, preferably a chloride ion.
  • Z + is connected via a linker group L to an insoluble carrier material T as a solid phase.
  • Z + has 4 or 5 radicals R, which are selected independently of one another from the group of alkyl, allyl, aryl and benzyl, C 1 -C 5 -alkyl being preferred. Particularly high yields of oxidized product are achieved when R 1 -R 4 or R 5 are methyl groups.
  • the carrier material T which is insoluble in the solvents usually used for organic syntheses, can be a polymer, in particular 1% divinylbenzene polystyrene resin.
  • T polycondensate of spherical polysilicic acids, also called silica gel.
  • the linker group L preferably has an ether group. However, it is also possible for L to be one or more amide, amine or Has ester groups or the like. Alkyl groups without heteroatoms are also conceivable as linker groups.
  • the oxoammonium salt consists of the above-mentioned positively charged 6-ring (a), a chloride ion, a CH 2 -0 linker group, the methylene group being linked to the insoluble carrier material T, and 1% divinylbenzene Polystyrene resin as an insoluble carrier material T.
  • polymer-bound oxoammonium salts have hitherto only been known as reactive intermediates in oxidations using TEMPO.
  • the compounds according to the invention are polymer-bound oxoammonium salts in isolated form. Such isolated salts are not known from the prior art.
  • oxoammonium salts according to claims 1-9, oxidations of various substrates are possible.
  • the salts described have proven to be particularly efficient in the oxidation of both aliphatic and benzylic alcohols. For example, a conversion of over 95% was achieved in the conversion of heptanol to heptanal.
  • ketones to diketones, diols to lactones and phenols to quinones can also be oxidized.
  • the inventive method for the oxidation of organic compounds according to claim 11 is characterized in that the compound to be oxidized is reacted with an oxoammonium salt according to the invention.
  • the oxoammonium salt is used in pure, isolated form, the formation of by-products, in particular of Overoxidation products, largely avoided.
  • product yields are achieved which are significantly higher than the yields achievable with the polymer-supported oxidizing agents known hitherto, such as the 1-hydroxy-4-oxo-2,2,6,6-tetramethylpiperidine from Carsten Bolm and Thomas Fey mentioned above.
  • the compound according to the invention when used in the polymer-assisted solution synthesis carried out here, offers the possibility of taking advantage of solid-phase synthesis, which dominated combinatorial chemistry in its first decade (combinatorial chemistry synthesis, analysis, screening, (publisher: G. Jung) , Wiley-VCH, Weinheim, 1999; Combinatorial Paptide and Non-Peptide Libraris, (ed .: G. Jung), VCH, Weinheim, 1996), with the advantages of synthesis in solution.
  • Polymeric reagents can be used in large excess and removed by filtration, whereas the products can easily be analyzed and further reacted in solution. Polymeric reagents are ideal for parallel combinatorial synthesis.
  • Oxoammonium resin 2 was prepared in a three-step synthesis from chloromethylated polystyrene resin and was used in the oxidation of alcohols 3a to 22a. The oxidation of resin 1 was carried out with Br 2 , Cl 2 or NCS / HCl.
  • Fig. 2 Collection of 20 chemically diverse alcohols 3a to 22a, which represent benzylic, allylic, primary aliphatic, secondary aliphatic alcohols and diols.
  • Fig. 3 GC analysis of the reaction of alcohol 9a in DCM (1 mg / ml) for 1 h with 1, 2 and 3 equivalents of the polymeric oxoammonium salt 2 using a flame ionization detector (FID).
  • FID flame ionization detector
  • Fig. 4 Secondary oxidation products of alcohols 3a to 22a.
  • Fig. 5 GC-FID of a mixture of 15 alcohols (top) and product mixture obtained after oxidation with resin 2 (bottom).
  • the 4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl radical was coupled with sodium hydride as a base to 1% divinylbenzene-polystyrene resin (Fig. 1). Elemental analysis of resin 1 showed a loading of 0.93 mmolg "1 of the radical. ESR spectroscopy confirmed the presence of the free radical electron and showed the characteristic triplet signal which is produced by the coupling with the 14 N core. Accordingly, the spectrum was in the HR-MAS NMR A clear broadening of the lines can be observed, which can be explained by the increased relaxation of the nuclear magnetization due to the interaction with the persistent electron spins ..
  • the resin was filtered off and washed thoroughly with water, water / DMF (1 : 1), DMF, THF, DCM (dichloromethane) and MeOH and dried in vacuo. Loading: 0.93 mmolg "1 chlorine content: 0.07%.
  • 11a lld 83 150 (M + ); 135; 122; 107; 95; 91; 82; 77; 54; 39
  • a compound collection consisting of 15 alcohols (3a-10a, 12a, 13a, 15a, 16a, 18a-20a) was used to investigate the implementation of complex mixtures of chemically diverse alcohols (Fig. 5).
  • the mixture (1 mgml "1 per alcohol) was analyzed by both GC-FID and GC-MS. In the starting mixture, all alcohols could be separated and identified by their mass spectrum.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne de nouveaux sels d'oxoammonium, leur utilisation, ainsi que de nouveaux procédés d'oxydation. Ces sels d'oxoammonium sont représentés par la formule générale T-L-Z+X-, dans laquelle T est un support insoluble, L est un groupe de liaison, Z+ représente a), b) ou c), R?1, R2, R3, R4 et R5¿ étant choisis indépendamment dans le groupe comprenant un groupe alkyle, un groupe allyle, un groupe aryle et un groupe benzyle, et X- est un contre-ion de l'ion d'oxoammonium.
EP02730001A 2001-03-16 2002-03-13 Sels d'oxoammonium et leur utilisation Withdrawn EP1368316A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10113710 2001-03-16
DE2001113710 DE10113710A1 (de) 2001-03-16 2001-03-16 Oxoammoniumsalze sowie deren Verwendung
PCT/EP2002/002762 WO2002074744A1 (fr) 2001-03-16 2002-03-13 Sels d'oxoammonium et leur utilisation

Publications (1)

Publication Number Publication Date
EP1368316A1 true EP1368316A1 (fr) 2003-12-10

Family

ID=7678365

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02730001A Withdrawn EP1368316A1 (fr) 2001-03-16 2002-03-13 Sels d'oxoammonium et leur utilisation

Country Status (3)

Country Link
EP (1) EP1368316A1 (fr)
DE (1) DE10113710A1 (fr)
WO (1) WO2002074744A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2003276010A1 (en) * 2002-10-07 2004-04-23 Ciba Specialty Chemicals Holding Inc. Oxoammonium salts of 1-oxy-2,2,6,6-tetramethyl-1-piperidine (tempo) and their use as oxidizing agents
JP6222776B2 (ja) 2011-04-21 2017-11-01 オリゲニス ゲーエムベーハーＯｒｉｇｅｎｉｓ Ｇｍｂｈ キナ−ゼ・インヒビタ−として有用なピラゾロ［４，３−ｄ］ピリミジン

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO02074744A1 *

Also Published As

Publication number Publication date
WO2002074744A1 (fr) 2002-09-26
DE10113710A1 (de) 2002-09-26

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