WO2008009674A1 - Procédé de synthèse d'esters d'acides carboxyliques à insaturation oléfinique - Google Patents
Procédé de synthèse d'esters d'acides carboxyliques à insaturation oléfinique Download PDFInfo
- Publication number
- WO2008009674A1 WO2008009674A1 PCT/EP2007/057366 EP2007057366W WO2008009674A1 WO 2008009674 A1 WO2008009674 A1 WO 2008009674A1 EP 2007057366 W EP2007057366 W EP 2007057366W WO 2008009674 A1 WO2008009674 A1 WO 2008009674A1
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- group
- alkyl
- process according
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- substituted
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- CULZFNOUPBWSIZ-UHFFFAOYSA-N CCOC(C=C(C(F)(F)F)C(F)(F)F)=O Chemical compound CCOC(C=C(C(F)(F)F)C(F)(F)F)=O CULZFNOUPBWSIZ-UHFFFAOYSA-N 0.000 description 1
- 0 CCOC(CC(*)(C(F)(F)F)C(F)(F)F)=O Chemical compound CCOC(CC(*)(C(F)(F)F)C(F)(F)F)=O 0.000 description 1
- ZVWBWGPBZGNCTP-UHFFFAOYSA-N CCOC(CC(C(F)(F)F)(C(F)(F)F)O)=O Chemical compound CCOC(CC(C(F)(F)F)(C(F)(F)F)O)=O ZVWBWGPBZGNCTP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/27—Preparation of carboxylic acid esters from ortho-esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C67/327—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups by elimination of functional groups containing oxygen only in singly bound form
Definitions
- the invention relates to a process for the synthesis of olefinically unsaturated carboxylic acid esters.
- the invention relates in particular to a process for the synthesis of olefinically unsaturated carboxylic acid esters by reacting carbonyl compounds with orthoesters of carboxylic acids.
- Olefinically unsaturated carboxylic acid esters are important intermediate products for the synthesis of for example insecticides and acaricides, and also for the synthesis of pharmaceutically active compounds.
- An important group among these compounds consists of fluorine containing olefinically unsaturated carboxylic acid esters.
- ethyl 4,4,4-trifluoro-3-trifluoromethyl crotonate (ETFMC) is an important intermediate for the synthesis of new pharmaceuticals. Only few synthesis routes are however described in the literature.
- DE 41 01 737 Al discloses a process for the production of olefinically unsaturated carboxylic acid esters by reacting carbonyl compounds and diazo compounds in the presence of a tertiary phosphine and a catalytic amount of an organo rhenium oxide in an organic solvent.
- hexafluoroacetone (HFA) is reacted with diazo acetic acid ethyl ester in toluene in the presence of CHsReO 3 and triphenyl phosphine to yield ETFMC.
- GB 2062620 A relates to haloalkyl cyclopropane carboxylic acid derivatives and their use as insecticides and acaricides.
- R 1 is an alkyl, aryl or heteroaryl group that may be substituted with one or more halogen atoms and/or Ci-C 3 -alkyl groups
- R 2 is an alkyl, aryl or heteroaryl group that may be substituted with one or more halogen atoms and/or Ci-C 3 -alkyl groups, or a hydrogen, or R 1 and R 2 form together with the carbon atom connecting them a C 4 -C 7 _carbocyclus that may be substituted with one or more halogen atoms and/or Ci_C 3 -alkyl groups
- R 3 is hydrogen or a C 1 -C 5 alkyl group
- halogen atoms used according to the present invention are in particular chlorine, fluorine or bromine atoms, most preferably fluorine atoms.
- R 1 and R 2 are independently from each other an alkyl, aryl or heteroaryl group that may be substituted with one or more halogen atoms and/or Ci-C 3 -alkyl groups.
- R 1 and/or R 2 is a fluorine containing Ci-Cs-alkyl group which contains in particular at least two fluorine atoms.
- the two fluorine containing Ci-Cs-alkyl group comprises preferably a CF 3 group, and most preferably, R 1 and/or R 2 is a CF 3 group.
- R 3 is hydrogen.
- R 4 is preferably a Ci-Cs-alkyl group, most preferably an ethyl group.
- the heteroaryl group present in the compounds used in the process according to the present invention contains in general one or more nitrogen, sulfur and/or oxygen atom.
- the aryl group present in the compounds used in the process according to the present invention comprises in particular a phenyl or naphthyl group.
- Ci-C 5 -alkyl groups according to the invention are in particular the methyl, ethyl, n-propyl, iso-propyl, n-butyl, t-butyl, n-pentyl or iso-pentyl group.
- the orthoesters of formula CH 2 R 3 C(OR 4 ) 3 are commercially obtainable or are synthetically readily available.
- trimethyl or triethyl orthoacetate and ethyl orthopropionate are available from DEGUSSA, Germany.
- the orthoesters of formula CH 2 R 3 C(OR 4 ) 3 are synthetically obtainable from the corresponding carboxylic esters by reacting the corresponding nitriles with the alcohol HOR 4 in the presence of HCl.
- further reaction in the second step of the intermediate compound R 1 R 2 COH-CHR 3 (COOR 4 ) can be carried out in the presence or absence of an organic solvent.
- an inert organic solvent is used.
- Suitable organic solvents are benzene, toluene, diethyl ether, dioxane, tetrahydrofurane, methylene chloride or chloroform.
- methylene chloride is used as the solvent.
- the most preferred alcohol is ethanol. It was found surprisingly that higher yields of the intermediate compound R 1 R 2 COH-CHR 3 (COOR 4 ) are obtained when ethanol is present in the reaction medium of the first step.
- R 1 R 2 COH-CHR ⁇ COOR 4 The product obtained after the first step, R 1 R 2 COH-CHR ⁇ COOR 4 ), may be isolated before the dehydration is carried out in a second step. Alternatively, the dehydration may be carried out in the same reaction medium. In a preferred - A -
- the product obtained after the first step is first isolated, and the second step is carried out separately.
- R 1 R 2 COH-CHR 3 (COOR 4 )
- the dehydration can be effected without the addition of a solvent or in the presence of a solvent.
- Suitable solvents are aprotic solvents, in particular acetonitrile, propionitrile and DMF.
- the OH-group in R 1 R 2 COH-CHR ⁇ COOR 4 is replaced by a better leaving group in order to facilitate the dehydration step.
- a suitable leaving group is the OC(O)CF 3 -group.
- the introduction of the leaving group for a preferred embodiment of the present invention can be expressed by the following reaction sequence (TFAC is CFsC(O)Cl) : °Vvv )
- the dehydration is carried out by firstly replacing the OH-group in R 1 R 2 COH-CHR ⁇ COOR 4 ) with a better leaving group which is then eliminated under formation of a double bond.
- a base is preferably used.
- Suitable bases are for example pyridine, pyrimidine, and
- R 1 R 2 COH-CHR ⁇ COOR 4 If the OH-group in R 1 R 2 COH-CHR ⁇ COOR 4 ) is replaced by a better leaving group, the introduction of the leaving group, for example by reacting R 1 R 2 COH-CHR 3 (COOR 4 ) with CF 3 C(O)Cl (TFAC), is preferably effected at a temperature of from O to 4O 0 C.
- TFAC CF 3 C(O)Cl
- ETFMC is produced by reacting in a first step hexafluoroacetone (HFA) with triethyl orthoacetate to an intermediate product which is then dehydrated in a second step to yield the desired ETFMC.
- HFA hexafluoroacetone
- the process of the present invention has several advantages.
- the process does neither require an expensive catalyst (like for example MeReO 3 ) nor a phosphine which would generate a large (stoechiometric) amount of phosphine oxide.
- the starting compounds are readily available.
- the process of the present invention allows to obtain the desired product in high yield.
- ETFMC was produced by reacting in a first step hexafluoroacetone (HFA) with triethyl orthoacetate to give ethyl 4,4,4-trifluoro-3-trifluoromethyl-3-hydroxy butanoate using an excess of HFA in either the absence of ethanol (Example Ia) or in the presence of ethanol (Example Ib).
- HFA hexafluoroacetone
- Example Ib ethanol
- Example Ib 82 g (0.49 mol) of ethyl orthoacetate were introduced in a conic reactor in Hastelloy B2 of a volume of 500 cc. The reactor was cooled down to -6O 0 C and 223.1 g (1.34 mol) of hexafluoroacetone were condensed into the reactor via a dipping tube. After the complete introduction of the hexafluoroacetone, the reactor temperature was set to 135 0 C during 5.5 h. The temperature was then further increased to 153 0 C during an additional period of 5 h.
- ETFMC ethyl 4,4,4-trifluoro-3-trifluoroacetyl-butanoate
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
L'invention concerne un procédé de synthèse d'esters d'acides carboxyliques à insaturation oléfinique de la formule R1R2C=CR3(COOR4), dans laquelle R1 est un groupe alkyle, aryle ou hétéroaryle qui peut être substitué par un ou plusieurs atomes d'halogène et/ou des groupes alkyle en C1-C3, R2 est un groupe alkyle, aryle ou hétéroaryle qui peut être substitué par un ou plusieurs atomes d'halogène et/ou des groupes alkyle en C1-C3, ou hydrogène, ou bien R1 et R2 forment conjointement avec l'atome de carbone les reliant un carocycle en C4-C7 qui peut être substitué par un ou plusieurs atomes d'halogène et/ou des groupe alkyle en C1-C3, R3 représente l'hydrogène ou un groupe alkyle en C1-C5, et R4 est un groupe alkyle ou aryle ayant jusqu'à 20 atomes de carbone, par réaction dans une première étape d'un composé carbonyle de formule R1R2C=O avec un orthoester de formule CH2R3C(OR4)3, et par déshydratation dans une seconde étape du composé intermédiaire obtenu R1R2COH-CHR3(COOR4).
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06117581 | 2006-07-20 | ||
EP06117581.6 | 2006-07-20 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2008009674A1 true WO2008009674A1 (fr) | 2008-01-24 |
Family
ID=37607228
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2007/057366 WO2008009674A1 (fr) | 2006-07-20 | 2007-07-17 | Procédé de synthèse d'esters d'acides carboxyliques à insaturation oléfinique |
Country Status (1)
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WO (1) | WO2008009674A1 (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102211999A (zh) * | 2011-05-25 | 2011-10-12 | 原平市同利化工有限责任公司 | 2-氟代丙烯酸烷基酯的制备方法 |
CN109790113A (zh) * | 2016-09-26 | 2019-05-21 | 3M创新有限公司 | 含氮和/或氧的氢氟烯烃及其制备和使用方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2062620A (en) * | 1979-10-23 | 1981-05-28 | Ici Ltd | Haloalkyl cyclopropane carboxylic acid derivatives |
DE4101737A1 (de) * | 1990-01-29 | 1991-08-01 | Hoechst Ag | Verfahren zur herstellung von olefinischen verbindungen aus carbonyl-verbindungen und diazoalkanen |
-
2007
- 2007-07-17 WO PCT/EP2007/057366 patent/WO2008009674A1/fr active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2062620A (en) * | 1979-10-23 | 1981-05-28 | Ici Ltd | Haloalkyl cyclopropane carboxylic acid derivatives |
DE4101737A1 (de) * | 1990-01-29 | 1991-08-01 | Hoechst Ag | Verfahren zur herstellung von olefinischen verbindungen aus carbonyl-verbindungen und diazoalkanen |
Non-Patent Citations (1)
Title |
---|
H. M. SAMPATH KUMAR, M. SHESHA RAO, SIPAK JOYASAWAL AND J. S. YADAV: "Condensation of orthoacetates with aldehydes: a new strategy for the preparation of alpha-beta-unsaturated esters", TETRAHEDRON LETTERS., vol. 44, no. 22, 26 May 2003 (2003-05-26), ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM., NL, pages 4287 - 4289, XP002415872 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102211999A (zh) * | 2011-05-25 | 2011-10-12 | 原平市同利化工有限责任公司 | 2-氟代丙烯酸烷基酯的制备方法 |
CN109790113A (zh) * | 2016-09-26 | 2019-05-21 | 3M创新有限公司 | 含氮和/或氧的氢氟烯烃及其制备和使用方法 |
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