EP1490327A1 - Production d'amino-crotonates - Google Patents

Production d'amino-crotonates

Info

Publication number
EP1490327A1
EP1490327A1 EP03711923A EP03711923A EP1490327A1 EP 1490327 A1 EP1490327 A1 EP 1490327A1 EP 03711923 A EP03711923 A EP 03711923A EP 03711923 A EP03711923 A EP 03711923A EP 1490327 A1 EP1490327 A1 EP 1490327A1
Authority
EP
European Patent Office
Prior art keywords
acid
onium
substituted
alkyl
phenyl
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Withdrawn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
EP03711923A
Other languages
German (de)
English (en)
Inventor
Max Braun
Saskia BRAUKMÜLLER
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.)
Solvay Fluor GmbH
Original Assignee
Solvay Fluor und Derivate 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 Solvay Fluor und Derivate GmbH filed Critical Solvay Fluor und Derivate GmbH
Publication of EP1490327A1 publication Critical patent/EP1490327A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/04—Formation of amino groups in compounds containing carboxyl groups
    • C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
    • C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups

Definitions

  • the invention relates to a simplified process for the preparation of 3-aminocrotonate compounds which are substituted on the C-4 atom by at least 2 chlorine and / or fluorine atoms.
  • Halogen-substituted 3-aminocrotonates are useful as intermediates, for example for dyes or photographic materials, as stated in the introduction to Japanese Patent Application 05-140 060.
  • a inocrotonates are also useful as intermediates for agrochemicals or pharmaceutical agents.
  • EP-A-0 808 826 teaches its preparation from haloacetoacetates and an ammonium salt.
  • the desired product is formed when heated. It is worked up by distillation, solvent / solvent extraction or solvent / water extraction.
  • WO 99/24390 teaches the production of halogenated aminocrotonates from haloacetoacetates and amines. Water formed during the reaction is removed by entrainer or inert gas passed through.
  • the object of the present invention is to provide an improved process for the preparation of halogenated aminocrotonates. This object is achieved by the method of the present invention.
  • the process according to the invention for producing 3-amino-crotonate compounds substituted on the C-4 atom by at least 2 chlorine and / or fluorine atoms by reacting acetoacetate compounds substituted on the C-4 atom by at least 2 chlorine and / or fluorine atoms with ammonia, primary or secondary amines with simultaneous or subsequent elimination of water provides that the preparation is carried out in the presence of "onium" salts which are formed from primary, secondary, tertiary or quaternary amines and carboxylic acids.
  • the method can be carried out in two embodiments, namely in such a way that one phase forms or in such a way that two phases form.
  • the invention is first further explained with regard to the embodiment in which two phases are formed, one phase containing the 3-amino-crotonate compound formed.
  • the water of reaction is in the phase containing the "onium” salt and cannot react with the product undesirably (saponification).
  • This embodiment is therefore particularly advantageous, also because of the simple workup of a 2-phase mixture.
  • Onium salts of ammonia and in particular salts of primary or secondary amines are preferably used. It is particularly advantageous to use those “onium” salts whose cation corresponds to the amine used to prepare the aminohalogen crotonate.
  • the method is particularly suitable for compounds in which the C-4 atom is substituted by two fluorine atoms, three fluorine atoms or one chlorine and two fluorine atoms.
  • the process according to the invention is preferably used to prepare aminohalogen crotonate compounds as disclosed in the aforementioned European patent application. It is a process for the preparation of a 3-amino-4, 4, 4-trihalogencrotonate compound of the formula (I)
  • X represents fluorine or chlorine
  • A represents O, S or NR 5 ;
  • B represents R 6 , OR 6 , SR 6 or NR 3 R 4 ;
  • R, R 1 , R 2 , R 3 , R 4 , R 5 and R ⁇ each independently of one another for H, (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, phenyl or phenyl ( C1-C6) alkyl; or for (Cl-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, phenyl or phenyl (C1-C6) alkyl, substituted with one or more groups independently selected from halogen, CN, NO 2 ; (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, phenyl, phenyl (C2-C6) alkyl, (C1-C6) alkoxy, (C2-C6) alkenyloxy and phenoxy; or R 1 and R 2 , and R 3 and R 4 can each independently be linked to the nitrogen to which they
  • CX 3 is preferably CF 3 , CF 2 C1 or CHF 2 .
  • R 1 and R 2 are the same or different and are preferably H, C1-C4-alkyl.
  • A is preferably 0 or S, in particular 0.
  • R is preferably H or Cl-C4-alkyl
  • B is preferably OR 6 or SR 6 .
  • R 3 , R 4 and R 5 are preferably H or C1-C3 alkyl.
  • R 6 is preferably C1-C3-alkyl and, if desired, can be substituted by 1 or more fluorine atoms.
  • onium preferably stands for cations with positively charged nitrogen, for example protonated aromatic nitrogen bases such as pyridinium or protonated alkyl, dialkyl or trialkylammonium cations or for ammonium compounds substituted by cycloalkyl or cycloaliphatic nitrogen bases such as piperidini or quaternary ammonium cations. These are protonated cations or quaternary cations of nitrogen.
  • R, R, R and R independently of one another represent hydrogen, alkyl having 1 to 20 carbon atoms, aryl or aralkyl.
  • R and R or R and R, or R, R and R or R, R, R and R can also, if appropriate including the nitrogen atom, form saturated or unsaturated ring systems.
  • Aryl here means in particular phenyl or phenyl substituted by 1 or more Cl-C2-alkyl groups.
  • R 1 ', R 2 ', R 3 'and R 4 ' independently of one another are hydrogen, alkyl are with 1 to 15 carbon atoms, phenyl or benzyl.
  • pyridinium, piperidinium, N-methylpiperidinium, anilinium, benzyltriethylammonium and triethylammonium may be mentioned.
  • Protonated cations of amines substituted by hydroxyl groups in particular cycloaliphatic amines, in particular hydroxy-substituted piperidines and N-Cl-C4-alkylpiperidines, can also be used.
  • hydroxyl groups in particular cycloaliphatic amines, in particular hydroxy-substituted piperidines and N-Cl-C4-alkylpiperidines.
  • the substituted on the C4 atom piperidines such as 4-hydroxypiperidine, N-methyl-4-hydroxypiperidine, N-ethyl-4-hydroxypiperidine and N-propyl-4-hydroxypiperidine.
  • Protonated cations of pyridine which is substituted by 1, 2, 3 or more alkyl groups having 1 to 4 carbon atoms are also useful.
  • Protonated cations of pyridine which is substituted by 1, 2 or 3 methyl or ethyl groups are preferred here.
  • Cations of picolines, lutidines and collidines, in particular 2-picoline, are preferred.
  • onocyclic ring systems that can be used are dialkylaminopyridine, dialkylaminopiperidine and dialkylaminopiperazine.
  • Onium cations of bicyclic compounds can also be used.
  • 1, 2 or more nitrogen atoms can be integrated into the ring system.
  • the compounds can be substituted by one or more amino groups.
  • Dialkyla ino groups are again preferred, the alkyl groups being the same or different and comprising 1 to 4 carbon atoms or together with the nitrogen atom forming a saturated ring system, such as the piperidinyl group.
  • At least 2 nitrogen atoms in the useful compounds must have basic properties and, depending on the type of bonds, are bound to 2 or 3 carbon atoms.
  • Anions of the "onium” salts are anions of carboxylic acids.
  • Preferred carboxylic acids, the anions of which are used are those having 1 to 6 carbon atoms.
  • Aliphatic, branched or unbranched carboxylic acid anions are particularly favorable, especially those with 1 to 4 carbon atoms, in particular if they are substituted by at least 1 halogen atom.
  • Anions which are derived from acetic acid or propionic acid and anions which are derived from acetic acid or propionic acid and which are min. at least 1 fluorine atom are substituted.
  • Anions of acetic acid, propionic acid, monofluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, chlorodifluoroacetic acid and perfluoropropionic acid are particularly suitable.
  • the "onium” salt can be prepared beforehand from amine and carboxylic acid, optionally with an excess of carboxylic acid. It is also possible to produce the "onium” salt in situ in the reactor. For example, one can saturate returned "onium” salt phase with amine and feed the carboxylic acid in the desired amount directly into the reactor.
  • an excess of carboxylic acid can also be used in the process according to the invention, both in the single-phase and in the two-phase variant.
  • the molar ratio of amine to carboxylic acid in the "onium" salt can range from about 1: 1 to 1: 8 or even higher.
  • the reaction is carried out in the temperature range from 40 to 140 ° C., depending on the rate of water elimination.
  • the molar ratio of "onium” salt to acetoacetate ester is advantageously in the range from 1: 0.5 to 1:40, particularly in the range from 1: 0.5 to 1:25, in particular in the range from 1: 1 to 1:25 ,
  • the range in which two phases form can vary depending on the "onium” salt used and the crotonate produced.
  • the amine is used only in an amount which is sufficient to convert up to 90 mol% of the acetoacetate, or for some amines up to 100 or even 140 mol%.
  • the 2-phase formation can be followed optically very well, and the person skilled in the art can easily estimate whether the formation of two phases in the respective Implementation is optimal. For example, you can add the "onium” salt, add the acetoacetate compound, and then gradually add the amine. It is easy to see the amounts of amine in one phase and the amounts of amine in two phases.
  • Water is formed when ammonia or amine is reacted with an acetoacetate compound.
  • the water accumulates in the salt phase. It can be done by vacuum distillation, the passage of inert gases such as nitrogen (this can also be air if desired), by membrane separation or other methods of water removal.
  • inert gases such as nitrogen (this can also be air if desired)
  • membrane separation or other methods of water removal.
  • inorganic, oxidic sorbents drying agents
  • Sorbents based on Si0 2 such as Sicolith 400 and AF 125 (AF means "aluminum-free") are well suited, these are dry pearls available from Engelhard Process Chemicals GmbH, Nienburg / Germany.
  • a noticeable difference in density is favorable for the formation of two phases.
  • the density of the crotonate formed is higher than the density of the "onium” salt, so that an "onium” salt with a lower density is advantageous. Therefore, salts with non-halogenated carboxylic acids are very useful.
  • the crotonate can be separated from the salt phase by decanting or other phase separation methods, e.g. B. Let the lower phase run out.
  • the process according to the invention produces a very pure crotonate even without additional distillation.
  • the salt phase can be used again, with occasional removal of the water of reaction.
  • the process is very selective.
  • the other embodiment is carried out in one phase.
  • the person skilled in the art can easily determine the single-phase area for a specific reaction. As already described above, he can add the "onium" salt, add the acetoacetate compound (ie the acetoester) and then gradually the amine, and then he can see in which area the reaction mixture forms a phase.
  • Both the single-phase and the two-phase embodiment can be carried out batchwise or continuously, the two-phase particularly well.
  • N-Me-EATC ethyl 3-methylamino-4,4,4,4-trifluorocrotonate
  • the amine was placed in a 500 ml flask and the TFA was carefully added dropwise at room temperature (exothermic reaction!). The mixture was then heated to about 50 ° C. and added dropwise to the ETFAA. The methylamine was introduced into the liquid at 85 ° C. (but only up to a conversion of approximately 80% ETFAA). When 75 mol% methylamine was reached, the NMe-EATC separated out as the main component of a second phase. Selectivity: 97.9% N-Me-EATC / 2, 1% N-Me-N-Me-ATCA.
  • the N-Me-EATC was then finally cleaned at a temperature of 62-64 ° C. and a pressure of 6 mbar (purity: 99.9 GC area percent).
  • the amine was placed in a 500 ml flask and the TFA was carefully added dropwise at room temperature (exothermic reaction!). The mixture was then heated to about 50 ° C. and added dropwise to the ETFAA. The methylamine was introduced into the liquid at 85 ° C. (but only up to a conversion of approximately 80% / 80 mol% of CH 3 NH 2 ).
  • the amine was placed in a 250 ml three-necked flask and the TFA was carefully added dropwise. Then the amount of H 2 0 was added. The mixture was then heated to approx. 80 ° C. N 2 was then blown in via a 1/8 inch hose (approx. 15-20 1 / h). The excess water was removed from the distillation head. The N 2 feed was carried out for 5 hours, with a sump sample taken every hour. In addition, the distillate was weighed out every hour.
  • Example 4 shows that the water can be removed from the salt phase by inert gas (which could also be air).
  • inert gas which could also be air.
  • the starting mixture had the following composition:
  • the example shows that the water can also be removed from the salt phase by distillation without changing the ratio of DBN to TFA.
  • the amine was placed in a 500 ml multi-necked flask and the acetic acid was added dropwise (exothermic reaction to 40 ° C.). The approach became fixed when added dropwise. The "onium” salt formed was subsequently dissolved at approx. 45 ° C.
  • the mixture was now kept at approx. 50 ° C. and added dropwise to the ETFAA.
  • the mixture was then heated to 85 ° C. and the methylamine was introduced.
  • N 2 was bubbled into the mixture in order to remove the excess water.
  • a two-phase range ranged from 50-100 mol% methylamine.
  • the mixture was thermolyzed at 85 ° C. for a further 1.5 hours while passing through N 2, and the batch was then distilled in vacuo.
  • the selectivity was quantitative.
  • NME-EATC was isolated with a purity of 99% at a temperature of 76 - 77 ° C and a vacuum of 60 mbar.
  • Example 5 was repeated with various "onium” salts. The respective areas of the 2-phase reaction and the yields are given.
  • the example could also be operated continuously, especially in the specified 2-phase range.

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

Abstract

Il est possible de produire des composés 3-amino-crotonate, par exemple des diesters, substitués au niveau de l'atome C-4 par au moins deux atomes de chlore ou de fluor, par réaction de composés acéto-acétate appropriés avec de l'ammoniac et des amines primaires et secondaires avec élimination d'eau simultanée ou consécutive. Ce faisant, la production a lieu en présence de sels « onium » qui sont formés à partir d'amines primaires ou secondaires et d'acides carboxyliques. Deux phases se forment de préférence, une phase contenant le composé crotonate formé à un degré de pureté élevé et l'autre phase contenant le sel « onium » et de l'eau.
EP03711923A 2002-03-21 2003-03-05 Production d'amino-crotonates Withdrawn EP1490327A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE10212525 2002-03-21
DE10212525 2002-03-21
DE10259911 2002-12-20
DE10259911 2002-12-20
PCT/EP2003/002228 WO2003080562A1 (fr) 2002-03-21 2003-03-05 Production d'amino-crotonates

Publications (1)

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EP1490327A1 true EP1490327A1 (fr) 2004-12-29

Family

ID=27806094

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Application Number Title Priority Date Filing Date
EP03711923A Withdrawn EP1490327A1 (fr) 2002-03-21 2003-03-05 Production d'amino-crotonates

Country Status (4)

Country Link
EP (1) EP1490327A1 (fr)
AU (1) AU2003218688A1 (fr)
DE (1) DE10309804A1 (fr)
WO (1) WO2003080562A1 (fr)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05140060A (ja) * 1991-11-13 1993-06-08 Nissan Chem Ind Ltd ３−置換アミノ−４，４，４−トリフルオロクロトン酸エステルの製造法
US5777154A (en) * 1996-11-14 1998-07-07 Rohm And Haas Company Method for preparing 3-amino substituted crotonates
AU728589B2 (en) * 1996-05-22 2001-01-11 Dow Agrosciences Llc A method for preparing 3-amino substituted crotonates
EP1028938B1 (fr) * 1997-11-07 2002-07-31 Solvay Fluor und Derivate GmbH Production de crotonates aminohalogenes

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03080562A1 *

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Publication number Publication date
AU2003218688A1 (en) 2003-10-08
DE10309804A1 (de) 2003-10-02
WO2003080562A1 (fr) 2003-10-02

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