WO2008038042A1 - Procédé chimique servant à déplacer des groupes nitro - Google Patents

Procédé chimique servant à déplacer des groupes nitro Download PDF

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Publication number
WO2008038042A1
WO2008038042A1 PCT/GB2007/050577 GB2007050577W WO2008038042A1 WO 2008038042 A1 WO2008038042 A1 WO 2008038042A1 GB 2007050577 W GB2007050577 W GB 2007050577W WO 2008038042 A1 WO2008038042 A1 WO 2008038042A1
Authority
WO
WIPO (PCT)
Prior art keywords
mixture
product
compound
nitro
displacing
Prior art date
Application number
PCT/GB2007/050577
Other languages
English (en)
Inventor
Michael Robert Pitts
David Joszef Tapolczay
Original Assignee
Phoenix Chemicals Limited
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 Phoenix Chemicals Limited filed Critical Phoenix Chemicals Limited
Publication of WO2008038042A1 publication Critical patent/WO2008038042A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms

Definitions

  • the present invention relates to an improved process for the displacement of a nitro group with a nitrogen nucleophile by using microwave assisted heating.
  • Microwave technology can be very useful for chemical processing, because reactants are heated directly instead of by convection and conduction, which are inefficient and can present their own problems during reactions.
  • the use of microwaves therefore reduces the total processing time and the risk of overheating and degradation of the product.
  • Microwave technology can also increase the reaction rate for a number of known reactions, with gains also found in yield.
  • An example of microwaves being used in chemical reactors can be illustrated by WO03/041856, which discloses a continuous flow heating system and a method of performing chemical reactions in a process fluid carried out in the system, whereby uniform heating is supplied to the reagents.
  • a process for displacing one or more nitro groups on a substrate compound with a heterocyclic compound comprising the steps: a) mixing the substrate compound with the heterocyclic compound to form a mixture; b) subjecting the mixture to microwave energy effective to heat the mixture to a temperature for a reaction time effective to allow the nitro displacement to take place and a product to be formed; c) recovering the product from the mixture; and optionally d) further purifying the product and/or processing it further.
  • the process therefore provides for a simple process for displacing a nitro group with a heterocycle, whose product is made in a high yield in a short period of time.
  • the nitrogen nucleophile displacing species may be selected from one of the following group: ammonia, secondary amines, secondary amides, and nitrogen containing heterocycles such as: pyrroles, imidazoles, pyrazoles, triazoles, pyrrolidines, pyrrolines, piperidines, piperazines, morpholines, and in particular 4-methylimidazole.
  • the process need not necessarily be limited to the displacement of one nitro group as a further nitro group may also be displaced by means of a possible side reaction. Therefore, two nitro groups may be displaced during the process.
  • the mixture will preferably be in a liquid phase and may be in the form of a slurry. Furthermore, the reaction may also take place in a high-boiling point, polar solvent, such as dimethylacetamide, dimethylformamide (DMF), dimethylsulfoxide (DMSO), N-methylpyrrolidinone (NMP).
  • polar solvent such as dimethylacetamide, dimethylformamide (DMF), dimethylsulfoxide (DMSO), N-methylpyrrolidinone (NMP).
  • the recovery of the product may be implemented by a number of ways that will be apparent to the person skilled in the art. It is preferred that the step of recovery comprises contacting the reacted mixture with a base in an aqueous solution and extracting the product with an organic solvent.
  • the organic base in an aqueous solution may comprise an aqueous ammonia solution for example or other such aqueous solutions of N,N,N',N'- tetramethylethylenediamine (TMEDA) or ethylediamine and any suitable organic solvent such as ether, tert-butylmethylether, ethyl acetate etc.
  • TMEDA N,N,N',N'- tetramethylethylenediamine
  • ethylediamine any suitable organic solvent such as ether, tert-butylmethylether, ethyl acetate etc.
  • the mixture may also further comprise an inorganic base, preferably potassium carbonate.
  • the resulting product may be purified by filtration and at least part of the filtration may comprise the passage of the product through a charcoal filter.
  • the process may involve a further step of: e) concentrating the product and optionally analysing the product.
  • the product can be analysed by a number of methods in order to assess the purity of the product and yield, such as by using high performance liquid chromatography (HPLC).
  • HPLC high performance liquid chromatography
  • microwave wavelength will depend upon the vessel that the reaction is being conducted in addition to the reaction type. However, it will be apparent that microwave wavelength should be capable of heating and is usually 2.45 GHz.
  • the reaction time of the present process is considerably reduced when compared to the prior art processes and preferably and the process may have a reaction time in the range of 60 to 600 seconds. More preferably, the reaction time is in the range of 100 to 400 seconds. Most preferably, the reaction time is approximately 300 seconds.
  • the mixture will preferably be heated to a temperature over 100 0 C. More preferably, the mixture is heated to a temperature in the range of 16O 0 C - 200 0 C. Most preferably, the mixture is heated to a temperature of approximately 18O 0 C.
  • the mixture may comprise a slurry of the substrate compound in 1.0 - 1.2 equivalent, the heterocyclic compound in 1.0 - 1.2 equivalent and the mediator compound in 0.5 - 2.0 equivalent.
  • the mixture may also be cooled prior to recovery.
  • the substrate compound may comprise any compound having at least one nitro group and capable of having the nitro group displaced by a heterocyclic compound.
  • the substrate compound may comprise 3,5-dinitrobenzotrifluoride.
  • the present process therefore provides for a novel process for displacing nitro groups with a nitrogen nucleophile using microwave-assisted heating, that results in considerably higher yields than in the parent process (>80%) at a similar ratio of 3/4 (92:8).
  • the crude material is comparable to the material after purification in the parent process. The reaction and overall processing times are also reduced.
  • the process may be used in the following scheme, whereby the reaction is mediated by potassium carbonate and is performed in a high-boiling solvent: 2

Landscapes

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

Abstract

La présente invention concerne un procédé servant à déplacer avec un composé hétérocyclique un ou plusieurs groupes nitro présents sur un composé substrat, comprenant les étapes consistant à : a) mélanger le composé substrat avec le composé hétérocyclique pour former un mélange ; b) soumettre le mélange à une énergie par micro-ondes efficace pour chauffer le mélange à une certaine température pendant une durée de réaction suffisante pour permettre au déplacement du groupe nitro d'avoir lieu et au produit de se former ; c) récupérer le produit du mélange ; et éventuellement d) purifier encore le produit et/ou transformer encore celui-ci. La présente invention concerne également un composé produit par le procédé.
PCT/GB2007/050577 2006-09-25 2007-09-24 Procédé chimique servant à déplacer des groupes nitro WO2008038042A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0618832.0 2006-09-25
GB0618832A GB0618832D0 (en) 2006-09-25 2006-09-25 Chemical process

Publications (1)

Publication Number Publication Date
WO2008038042A1 true WO2008038042A1 (fr) 2008-04-03

Family

ID=37421557

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2007/050577 WO2008038042A1 (fr) 2006-09-25 2007-09-24 Procédé chimique servant à déplacer des groupes nitro

Country Status (2)

Country Link
GB (1) GB0618832D0 (fr)
WO (1) WO2008038042A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10392351B2 (en) 2014-01-07 2019-08-27 Suzhou Lixin Pharmaceutical Co., Ltd. Method for preparing nilotinib intermediate

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050178650A1 (en) * 2002-04-29 2005-08-18 Basf Aktiengesellschaft Method for producing organic alkyne compounds
WO2006135619A1 (fr) * 2005-06-09 2006-12-21 Novartis Ag Procede destine a la synthese de 5-(methyl-1h-imidazol-1-yl)-3-(trifluoromethyl)-benzeneamine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050178650A1 (en) * 2002-04-29 2005-08-18 Basf Aktiengesellschaft Method for producing organic alkyne compounds
WO2006135619A1 (fr) * 2005-06-09 2006-12-21 Novartis Ag Procede destine a la synthese de 5-(methyl-1h-imidazol-1-yl)-3-(trifluoromethyl)-benzeneamine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KIYOMORI A ET AL: "An Efficient Copper-Catalyzed Coupling of Aryl Halides with Imidazoles", TETRAHEDRON LETTERS, ELSEVIER, AMSTERDAM, NL, vol. 40, no. 14, 2 April 1999 (1999-04-02), pages 2657 - 2660, XP004159403, ISSN: 0040-4039 *
PARK S K ET AL: "SYNTHESIS OF POLY(ARYLENE ETHER KETONE)S CONTAINING TRIFLUOROMETHYLGROUPS VIA NITRO DISPLACEMENT RACTION", MACROMOLECULES, ACS, WASHINGTON, DC, US, vol. 31, no. 10, 19 May 1998 (1998-05-19), pages 3385 - 3387, XP000750161, ISSN: 0024-9297 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10392351B2 (en) 2014-01-07 2019-08-27 Suzhou Lixin Pharmaceutical Co., Ltd. Method for preparing nilotinib intermediate

Also Published As

Publication number Publication date
GB0618832D0 (en) 2006-11-01

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