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DE2103749A1 - 3-acyl-acrylic acids prepn - from a ketone and glyoxylic acid (deriv) - Google Patents

3-acyl-acrylic acids prepn - from a ketone and glyoxylic acid (deriv)

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Publication number
DE2103749A1
DE2103749A1 DE19712103749 DE2103749A DE2103749A1 DE 2103749 A1 DE2103749 A1 DE 2103749A1 DE 19712103749 DE19712103749 DE 19712103749 DE 2103749 A DE2103749 A DE 2103749A DE 2103749 A1 DE2103749 A1 DE 2103749A1
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Prior art keywords
lower alkyl
acid
general formula
radical
alkyl radical
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DE19712103749
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Inventor
Wolfhard Dipl.-Chem. Dr.; Seeger Ernst Dipl.-Chem. Dr.; Teufel Helmut Dipl.-Chem. Dr.; Nicki Josef Dipl.-Chem. Dr.; 7950 Biberach Engel
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Boehringer Ingelheim Pharma GmbH and Co KG
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Dr Karl Thomae GmbH
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Priority to DE19712103749 priority Critical patent/DE2103749A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
    • C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C255/46—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/373—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in doubly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/76—Unsaturated compounds containing keto groups
    • C07C59/86—Unsaturated compounds containing keto groups containing six-membered aromatic rings and other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/76—Unsaturated compounds containing keto groups
    • C07C59/88—Unsaturated compounds containing keto groups containing halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/76—Unsaturated compounds containing keto groups
    • C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

3-Acyl-acrylic acids of formula (I):- (in which A is aryl or heteroaryl opt. substd. by lower alkyl; R1 and R2 same or different, are H, lower alkyl, opt. substd. aroyl, halogen, NO2, acetylamino, CN, carbamoyl opt. substd. by one or more alkyl, carboalkoxy, OH, alkoxy, alkylthio, or alkylsulphenyl, or one of R1 and R2 may be cycloalkyl or cycloalkenyl opt. substd. by CN or alkyl, allyloxy, dialkylaminoalkyl, heteroaryl opt. hydrated, aryl opt. substd. by lower alkyl, halogen, NO2, acetylamino, CN, carbamoyl which may be substd. by one or more alkyl, carboalkoxy, OH, alkoxy, alkylthio or alkylsulphenyl, and R3 is H or lower alkyl) comprises reacting a ketone of formula (II): with a glyoxylic acid or its deriv. of formula (III): (in which R4 is H or lower alkyl; R5 and R6, same or different, are H, lower alkyl, or together form alkylene) in presence of acid condensation agent at 50 - 200 degrees C. Cpds. (I) are inters. for antiinflammatory and antitussive crotonic acid cpds.

Description

Verfahren zur Herstellung von neuen 3-Acyl-acrylsäure Zusatz zum DBP....(Patentanmeldung P P 20 47 806.2j7 12,(21 (67, 17 @ Im DBP.......(Aktenzeichen P P 20 47 806.2) wird erstmals ein allgemein anwendbares einstufiges Verfahren zur Herstellung von 3-Acyl-acrylsäuren beschrieben. Es wurde nun festgestellt, daß sich die bisher nicht beschriebenen 3-Acyl-acrylsäuren der allgemeinen Formel in der einen Alkylrest, einen gegebenenfalls durch eine Cyangr@ oder einen niederen Alkylrest substituierten Cycloalkyl Cycloalkenylrest und R2 ein Halogenatom, eine Nitro- oder niedere Alkoxygruppe o sofern R1 einen Cycloalkenyl- oder einen durch eine Cy::rgruppe substituierten Cycloalkylrest darstellt, auch ei Wasserstoffatom bedeuten, nach dem gleichen Verfahren herstellen lassen.Process for the production of new 3-acyl-acrylic acid addition to the DBP .... (patent application PP 20 47 806.2j7 12, (21 (67, 17 @ Im DBP ....... (file number PP 20 47 806.2) For the first time a generally applicable one-step process for the preparation of 3-acyl-acrylic acids was described It has now been found that the 3-acyl-acrylic acids not previously described have the general formula in which an alkyl radical, a cycloalkyl cycloalkenyl radical optionally substituted by a cyang group or a lower alkyl radical, and R2 a halogen atom, a nitro or lower alkoxy group, if R1 is a cycloalkenyl or a cycloalkyl radical substituted by a cyano group, also a hydrogen atom mean to have made by the same process.

Gegenstand der vorliegenden Anmeldung sind somit die ne-3-Acyl-acrylsäuren der obigen allgemeinen Formel I, welche wertvolle Zwischenprodukte insbesondere zur Herstellung von Pharmaceutica darstellen. Diese lassen sich nach folgendem Verfahren herstellen: Umsetzung eines Ketons der allgemeinen Formel in der R1 und R2 wie eingangs definiert sind, mit Glyoxylsäure oder einem Derivat der allgemeinen Formel in der R3 ein Wasserstoffatom oder einen niederen Alkylrest, R4 und R5, die gleich oder verschieden sein können, Wassersto atome oder niedere Alkylreste oder die Reste R4 und R zuW einen Alkylenrest bedeuten, in Gegenwart eines sauren Konde-.-sationsmittels.The present application thus relates to the ne-3-acyl-acrylic acids of the above general formula I, which are valuable intermediates, in particular for the production of pharmaceuticals. These can be produced by the following process: Implementation of a ketone of the general formula in which R1 and R2 are as defined at the outset, with glyoxylic acid or a derivative of the general formula in which R3 is a hydrogen atom or a lower alkyl radical, R4 and R5, which may be the same or different, hydrogen atoms or lower alkyl radicals, or the radicals R4 and R zuW mean an alkylene radical, in the presence of an acidic condensation agent.

Die Umsetzung wird in Gegenwart eines sauren Kondensationsmittels zweckmäßigerweise mit einem geringen Überschuß an Glyoxylsäure oder einem Derivat der allgemeinen Formel III vorzugsweise fl einem Lösungsmittel, z. B. in Dioxan, Äthylenglykoldimethyläther oder Diäthylenglykoldimethyläther, und beispielsweise bei Temperaturen zwischen 500 und 2000C, vorzugsweise bei 800 -420°C, durchgeführt. Als saure Kondensationsmittel kommen anorganische oder organische Säuren in Betracht, beispielsweise Ameisensäure, Essigsäure, Propionsäure, Oxalsäure, Trifluoressigsäure, -phatische oder aromatische Sulfonsäuren, Phosphorsäure, Peroklo»-säure, Schwefelsäure oder Salzsäure; hierbei kann das Kondensationsmittel selbst als Lösungsmittel dienen.The reaction is carried out in the presence of an acidic condensing agent expediently with a small excess of glyoxylic acid or a derivative of the general formula III preferably fl a solvent, for. B. in dioxane, Ethylene glycol dimethyl ether or diethylene glycol dimethyl ether, and for example at temperatures between 500 and 2000C, preferably at 800-420 ° C carried out. Inorganic or organic acids are suitable as acidic condensing agents, for example formic acid, acetic acid, propionic acid, oxalic acid, trifluoroacetic acid, -phatic or aromatic sulphonic acids, phosphoric acid, peroclonic acid, sulfuric acid or hydrochloric acid; here the condensation agent itself can serve as a solvent.

Bedeutet R3 einen niederen Alkylrest, so wird die Umsetzung vorzugsweise in einer niederen aliphatischen Carbonsäure als Losungsmittel, z. B. in Ameisensäure oder Essigsäure, und in Gegenwart einer starken Säure, z. B. von p-Toluolsulfonsäure, durcngeführt; bei der Umsetzung tritt gleichzeitig Umesterung ein.If R3 is a lower alkyl radical, the reaction is preferred in a lower aliphatic carboxylic acid as solvent, e.g. B. in formic acid or acetic acid, and in the presence of a strong acid, e.g. B. of p-toluenesulfonic acid, carried out; during the implementation, transesterification occurs at the same time.

Die Umsetzung kann aber auch am Wasserabscheider, z. B. in Xylol und in Gegenwart von p-Toluolsulfonsäure, durchgeführt werden.However, the implementation can also be carried out on the water separator, e.g. B. in xylene and in the presence of p-toluenesulfonic acid.

Ferner ist es von Vorteil, wenn der Ablauf der Umsetzung dünnschichtchromatographisch verfolgt wird. Die Umsetzung ist beendet, wenn sich die intermediär bildende α-Hydroxy-γ-oxobuttersäure nicht mehr nachweisen läßt.It is also advantageous if the course of the reaction is carried out by thin-layer chromatography is pursued. The reaction is complete when the intermediate α-hydroxy-γ-oxobutyric acid is formed can no longer be proven.

Die erhaltenen Verbindungen der allgemeinen Formel 1 können anschließend gewünschtenfalls in ihre Salze mit anorganischen oder tertiären organischen Basen übergeführt werden.The compounds of general formula 1 obtained can then if desired into their salts with inorganic or tertiary organic bases be transferred.

Die als Ausgangsstoffe verwendeten Ketone der allgemeinen rmel II sind teilweise literaturbekannt oder können nach bekannten Verfahren hergestellt werden. Beispielsweise wurden folgende zum Teil neue Ketone der allgemeinen Formel II hergestellt: 4'-Cyclohexyl-3'-fluor-acetophenon, Schmelzpunk:41-42ºC 3'-Chlor-4'-cyclohexyl-acetophenon, Kp. 1.5:135-139ºC 3'-Brom-4'-cyclohexyl-acetophenon, Kp. 0,15: 135-138ºC 4'-Cyclohexyl-3'-methoxy-acetophenon, Schmelzpunkt: 69-70°C 3'-Chlor-4'-cyclopentyl-acetophenon, Kp. 0,2: 134-1400C 3'-Chlor-4'-cycloheptyl-acetophenon, Kp. 0,1: 136-179°C 4'-(1-Cyclohexen-1-yl)-acetophenon, Schmelzpunkt:75-76ºC 4'-Cyclohexyl-3'-nitro-acetophenon, Schmelzpunkt: 64-65°C 4'-(1-Cyan-1-cyclohexyl)-acetophenon, Kp.0,1: 156-158ºC 3'-Chlor-4'-(1-methyl-1-cyclohexyl)-acetophenon, Kp.0,35: 137-140ºC 4'-Isopropyl-3'-nitro-acetophenon, Schmelzpunkt: 47-480C Wie bereits eingangs erwähnt, stellen die neuen Verbindunger der allgemeinen Formel I wertvolle Zwischenprodukte zur Herstellung von Pharmaceutica mit entzUndungshemmender und hustenstillender Wirksamkeit, insbesondere zur Herstellung der e.~ sprechenden 4-Hydroxy-crotonsäuren,dar. Die Eigenschaften dieser Verbindungen sind also in den neuen Zwischenprodukten immanent.The ketones of general sleeve II used as starting materials are partly known from the literature or can be prepared by known processes will. For example, the following ketones, some of which are new, have the general formula II prepared: 4'-Cyclohexyl-3'-fluoro-acetophenone, melting point: 41-42 ° C 3'-chloro-4'-cyclohexyl-acetophenone, B.p. 1.5: 135-139 ° C 3'-bromo-4'-cyclohexyl-acetophenone, b.p. 0.15: 135-138 ° C 4'-cyclohexyl-3'-methoxy-acetophenone, Melting point: 69-70 ° C 3'-chloro-4'-cyclopentyl-acetophenone, boiling point 0.2: 134-1400C 3'-chloro-4'-cycloheptyl-acetophenone, Bp 0.1: 136-179 ° C 4 '- (1-Cyclohexen-1-yl) -acetophenone, melting point: 75-76 ° C 4'-cyclohexyl-3'-nitro-acetophenone, Melting point: 64-65 ° C 4 '- (1-cyano-1-cyclohexyl) -acetophenone, b.p. 0.1: 156-158 ° C 3'-chloro-4' - (1-methyl-1-cyclohexyl) -acetophenone , Bp 0.35: 137-140 ° C 4'-Isopropyl-3'-nitro-acetophenone, melting point: 47-480C As already mentioned at the beginning, represent the new compounds of the general formula I valuable intermediates for the manufacture of Pharmaceutica with anti-inflammatory and antitussive efficacy, especially for the production of the e. ~ speaking 4-hydroxy-crotonic acids. The properties of these compounds are therefore in the intrinsic to new intermediates.

Die nachfolgenden Beispiele sollen die Erfindung näher erläutern: Beispiel 1 3-(3-Chlor-4-cyclohexyl-benzoyl)-acrylsäure 134,0 g (0,566 Mol) 3'Chlor-4)cyclohexyl-acetophenon in 700 ml Ameisensäure werden mit 55,0 g (0,598 Mol) Glyoxylsäurehydrat versetzt und unter Rückfluß gekocht. Nach 24 Stunden gibt man weitere 5,5 g (0,06 Mol) Glyoxylsäurehydrat zu und kocht abermals 24 Stunden. Nach dieser Zeit ist die als Zwischenstufe auftretende ß-(3-Chlor-4-cyclohexyl-benzoyl)-α-hydroxy-propionsäure duflflschichtchromatographisch nicht mehr nachzuweisen. Man läßt erkalten, rührt in 3 1 Eiswasser ein und nimmt das abgeschiedene Produkt in Essigsäureäthylester auf. Man wäscht die organische Phase einmal mit Wasser, trocknet sie über Natriumsulfat, filtriert u. dampft im Vakuum ein. Der Rückstand kristallisiert beim Anreiben mit Petroläther/Cyclohexan (1:1). Die Kristalle werden abgenutscht und aus einem Gemisch von Benzol/ Cyclohexan (1:5) umkristallisiert. Man erhält 40,3 g fahlgelbe Kristalle vom Schmelzpunkt 112-113°C.The following examples are intended to explain the invention in more detail: Example 1 3- (3-Chloro-4-cyclohexyl-benzoyl) -acrylic acid 134.0 g (0.566 mol) 3'-chloro-4) cyclohexyl-acetophenone 55.0 g (0.598 mol) of glyoxylic acid hydrate are added to 700 ml of formic acid and refluxed. After 24 hours, a further 5.5 g (0.06 mol) of glyoxylic acid hydrate are added and cooks again for 24 hours. After this time is the one that occurs as an intermediate stage ß- (3-chloro-4-cyclohexyl-benzoyl) -α-hydroxy-propionic acid by double-layer chromatography no longer to be proven. It is allowed to cool, stirred into 3 l of ice water and taken the deposited product in ethyl acetate. One washes the organic Phase once with water, dry it over sodium sulfate, filter and evaporate in the Vacuum a. The residue crystallizes on trituration with petroleum ether / cyclohexane (1: 1). The crystals are suction filtered and made from a mixture of benzene / cyclohexane (1: 5) recrystallized. 40.3 g of pale yellow crystals with a melting point of 112-113 ° C. are obtained.

Ähnliche Ergebnisse erzielt man bei Verwendung von Essigsäure, Propionsäure, 85%iger Phosphorsäure in Gegenwart von Dioxan als Lösungsmittel, konzentrierter Salzsäure/Dioxan, 80%iger Schtzefelsäure/Dioxan oder Oxalsäure/Dioxan als Kondensationbmittel.Similar results are obtained when using acetic acid, propionic acid, 85% phosphoric acid in the presence of dioxane as solvent, more concentrated Hydrochloric acid / dioxane, 80% strength acid / dioxane or oxalic acid / dioxane as condensation agents.

Beispiel 2 3-(3-Chlor-4-cyclohexyl-benzoyl)-acrylsäure Das Gemisch aus 47,35 g (0,20 Mol) 3'-Chlor-41-cyclohexylacetophenon, 26,8 g (0,20 Mol) Dimethoxy-essigsäuremethylester, 200 ml Ameisensäure und 0,3 ml konzentrierter Schwefelsäure wird zum Sieden erhitzt, so daß über eine 30 cm lange Vigreux-Kolonne der entstehende Ameisensäuremethylester langsam mit möglichst wenig Amseisensäure abdestilliert. Nach 8 Stunden gibt man nochmals 13,4 g (0,10 Mol) Dimethoxy-essigsäuremethylester zu und erwärmt weitere 12 Stunden. Anschließend wird die Reaktionsmischung in 1 1 Eiswasser eingerührt.Man extrahiert das erhaltene Produkt mit insgesamt 500 ml eines Gemisches aus gleichen Teilen Essigester und Benzol. Man trennt die organische Phase ab, trocknet diese über Natriumsulfat und filtriert sie über 300 g Kieselgel.Example 2 3- (3-chloro-4-cyclohexyl-benzoyl) acrylic acid The mixture from 47.35 g (0.20 mol) 3'-chloro-41-cyclohexylacetophenone, 26.8 g (0.20 mol) dimethoxy-acetic acid methyl ester, 200 ml of formic acid and 0.3 ml of concentrated sulfuric acid are heated to the boil, so that the methyl formate formed is passed through a 30 cm long Vigreux column slowly distilled off with as little formic acid as possible. After 8 hours you give 13.4 g (0.10 mol) of methyl dimethoxyacetate are added and more is heated 12 hours. The reaction mixture is then stirred into 1 l of ice water extracted the product obtained with a total of 500 ml of a mixture of the same Share ethyl acetate and benzene. The organic phase is separated off and dried over sodium sulfate and filtered through 300 g of silica gel.

Das Lösungsmittel wird im Vakuum entfernt und der erhaltene Rückstand aus Benzol/Cyclohexan (1:5) umkristallisiert.The solvent is removed in vacuo and the residue obtained recrystallized from benzene / cyclohexane (1: 5).

Ausbeute: 10,74 g Schmelzpunkt: 111-1130C Analog den Beispielen 1-2 wurden folgende Verbindungen hergestellt: 3-(4-Cyclohexyl-3-fluor-benzoyl)-acrylsäure Schmelzpunkt: 111-112°C (aus Cyclohexan) 3-(3-Brom-4-cyclohexyl-benzoyl)-acrylsäure Schmelzpunkt: 120-121 0C (aus Cyclohexan unter Verwendung von Aktivkohle) 3-(4-Cyclohexyl-3-methoxy-benzoyl)-acrylsäure Schmelzpunkt: 160-161°C (aus Benzol) 3-(3-Chlor-4-cyclohexyl-benzoyl)-acrylsäure Schmelzpunkt: 127-128°C (aus Cyclohexan) 3-(3-Chlor-4-cyclohexyl-benzoyl)-acrylsäure gelbes Öl, IR-Spektrum: C=O-Bande bei 1710 und 1675 cm 1, C=C-Bande bei 1600 cm 1 3-[4-(1-Cyclohexen-1-yl)-benzoyl]-acrylsäure Schmelzpunkt: 150-153ºC 3-[4-(1-Cyan-cyclohexyl)-benzoyl]-acrylsäure gelbes, viskoses Öl; IR-Spektrum: C=O-Bande bei 1705 und 1670 cm 1 C=C-Bande bei 1600 cm 3-[3-Chlor-4-(1-methyl-cyclohexyl)-benzoyl]-acrylsäure Schmelzpunkt: 167-1690C (aus Essigsäureäthylester) 3-(4-Cyclohexyl-3-nitro-benzoyl)-acrylsäure Schmelzpunkt: 158-1 600C (aus Tetrachlorkohlenstoff) 3-(4-Isopropyl-3-nitro-benzoyl)-acrylsäure Schmelzpunkt: 155-156ºC (aus Essigsäureäthylester)Yield: 10.74 g Melting point: 111-1130C Analogously to Examples 1-2 the following compounds were produced: 3- (4-Cyclohexyl-3-fluoro-benzoyl) acrylic acid Melting point: 111-112 ° C (from cyclohexane) 3- (3-bromo-4-cyclohexyl-benzoyl) acrylic acid Melting point: 120-121 ° C. (from cyclohexane using activated carbon) 3- (4-cyclohexyl-3-methoxy-benzoyl) acrylic acid Melting point: 160-161 ° C (from benzene) 3- (3-chloro-4-cyclohexyl-benzoyl) acrylic acid Melting point: 127-128 ° C (from cyclohexane) 3- (3-chloro-4-cyclohexylbenzoyl) acrylic acid yellow oil, IR spectrum: C = O band at 1710 and 1675 cm 1, C = C band at 1600 cm 1 3- [4- (1-Cyclohexen-1-yl) -benzoyl] -acrylic acid Melting point: 150-153 ° C 3- [4- (1-Cyano-cyclohexyl) -benzoyl] -acrylic acid yellow, viscous oil; IR spectrum: C = O band at 1705 and 1670 cm 1 C = C band at 1600 cm 3- [3-chloro-4- (1-methyl-cyclohexyl) -benzoyl] -acrylic acid. Melting point: 167-1690C (from ethyl acetate) 3- (4-Cyclohexyl-3-nitro-benzoyl) acrylic acid Melting point: 158-1600C (from carbon tetrachloride) 3- (4-isopropyl-3-nitro-benzoyl) acrylic acid Melting point: 155-156 ° C (from ethyl acetate)

Claims (6)

P a t e n t a n s p r ü c h e 1.Verfahren zur Herstellung von neuen 3-Acyl-acrylsäuren der allgemeinen Formel in der R1 einen Alkylrest, einen gegebenenfalls durch eine Cyangruppe oder einen niederen Alkylrest substituierten Cycloalkyl- oder Cycloalkenylrest und R2 ein Halogenatom, eine Nitro- oder niedere Alkoxygruppe oder, sofern R1 einen Cycloalkenyl- oder einen durch eine Cyangruppe substituierten Cycloalkylrest darstellt, auch ein Wasserstoffatom bedeuten, sowie von deren Salzen mit anorganischen oder tertiären organischen Basen gemäß DBP.........P atent claims 1. Process for the preparation of new 3-acyl-acrylic acids of the general formula in which R1 is an alkyl radical, a cycloalkyl or cycloalkenyl radical optionally substituted by a cyano group or a lower alkyl radical and R2 is a halogen atom, a nitro or lower alkoxy group or, if R1 is a cycloalkenyl or a cycloalkyl radical substituted by a cyano group, also a hydrogen atom mean, as well as their salts with inorganic or tertiary organic bases according to DBP ......... (Aktenzeichen P 20 47 806.2), dadurch gekennzeichnet, daß ein Keton der allgemeinen Formel in der R1 und R2 wie eingangs definiert sind, mit Glyoxylsäure oder einem Derivat der allgemeinen Formel in der R3 ein Wasserstoffatom oder einen niederen Alkylrest, R4 und R5, die gleich oder verschieden sein können, Wasserstoffatome oder niedere Alkylreste oder die Reste R4 und R zusammen 5 einen Alkylenrest bedeuten, in Gegenwart eines sauren Kondensationsmittels bei Temperaturen zwischen 500 und 2000C umgesetzt wird und gewünschtenfalls anschließend die erhaltene Verbindung der allgemeinen Formel I in ihr Salz mit einer anorganischen oder tertiären organischen Base übergeführt wird.(File number P 20 47 806.2), characterized in that a ketone of the general formula in which R1 and R2 are as defined at the outset, with glyoxylic acid or a derivative of the general formula in which R3 is a hydrogen atom or a lower alkyl radical, R4 and R5, which may be the same or different, hydrogen atoms or lower alkyl radicals or the radicals R4 and R together 5 are an alkylene radical, is reacted in the presence of an acidic condensing agent at temperatures between 500 and 2000C and, if desired, the compound of the general formula I obtained is then converted into its salt with an inorganic or tertiary organic base. 2. Verfahren gemäß Anspruch 1, dadurch gekennzeichnet, daß die Umsetzung in einem Lösungsmittel durchgeführt wird.2. The method according to claim 1, characterized in that the implementation is carried out in a solvent. 3. Verfahren gemäß Anspruch 1, dadurch gekennzeichnet, daß als Kondensationsmittel eine anorganische oder organische Säure verwendet wird.3. The method according to claim 1, characterized in that the condensation agent an inorganic or organic acid is used. 4. Verfahren gemäß Anspruch 1,2 und 3, dadurch gekennzeichnet, daß als Lösungsmittel eine aliphatische Carbonsäure verwendet wird, falls R4 einen niederen Alkylrest bedeutet.4. The method according to claim 1, 2 and 3, characterized in that an aliphatic carboxylic acid is used as the solvent if R4 is lower Means alkyl radical. 5. Verfahren gemäß Anspruch 1, 2, 3 und 4, dadurch gekennzeichnet, daß die Umsetzung bei Temperaturen zwischen 800 und 1200C durchgeführt wird.5. The method according to claim 1, 2, 3 and 4, characterized in that that the reaction is carried out at temperatures between 800 and 1200C. 6. Neue 3-Acyl-arylsäuren der allgemeinen Formel I in der R1 einen Alkylrest, einen gegebenenfalls durch eine Cyangruppe oder einen niederen Alkylrest substituierten Cycloalkyl-oder Cycloalkenylrest und R2 ein Halogenatom, eine Nitro- oder niedere Alkoxygruppe oder, sofern R1 einen Cycloalkenyl- oder einen durch eine Cyangruppe substituierten Cycloalkylrest darstellt, auch ein Wasserstoffatom bedeuten und deren Salze mit anorganischen oder tertiären organischen Basen.6. New 3-acyl-aryl acids of the general formula I. in which R1 is an alkyl radical, a cycloalkyl or cycloalkenyl radical optionally substituted by a cyano group or a lower alkyl radical and R2 is a halogen atom, a nitro or lower alkoxy group or, if R1 is a cycloalkenyl or a cycloalkyl radical substituted by a cyano group, also a hydrogen atom mean and their salts with inorganic or tertiary organic bases.
DE19712103749 1971-01-27 1971-01-27 3-acyl-acrylic acids prepn - from a ketone and glyoxylic acid (deriv) Pending DE2103749A1 (en)

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2513157A1 (en) * 1974-03-25 1975-10-09 Fabre Sa Pierre AROMATIC KETO ACIDS AND THEIR DERIVATIVES
FR2481270A1 (en) * 1980-04-24 1981-10-30 Roussel Uclaf NOVEL SUBSTITUTED DERIVATIVES OF 4-PHENYL 4-OXO 2-HYDROXY BUTANOIC ACID, PROCESS FOR THEIR PREPARATION AND APPLICATIONS AS MEDICAMENTS
DE3214081A1 (en) * 1981-04-17 1982-11-04 Roussel-Uclaf, 75007 Paris USE OF PHENYL ALIPHATIC CARBONIC ACID DERIVATIVES AS A MEDICINAL PRODUCT
US4454155A (en) * 1981-10-22 1984-06-12 Roussel Uclaf Pharmaceutical compositions containing a mono-substituted derivative of 4-phenyl-4-oxobuten-2-oic acid, and methods of using them in treating gastric and gastroduodenal ailments
US4473583A (en) * 1981-10-22 1984-09-25 Roussel Uclaf Compositions containing certain derivatives of 4-phenyl-4-oxobuten-2-oic acid and methods of treatment using them
US4483868A (en) * 1980-04-24 1984-11-20 Roussel Uclaf Gastro-protecting activity
US4486429A (en) * 1981-10-22 1984-12-04 Roussel Uclaf Amino derivatives of 4-phenyl 4-oxobuten-2-oic acid, pharmaceutical compositions containing them, and methods for preparing and therapeutically using them
US4594443A (en) * 1983-08-25 1986-06-10 Roussel-Uclaf Derivatives of 4-phenyl-4-oxo-buten-2-oic acid and therapeutic use thereof
US4814348A (en) * 1983-01-24 1989-03-21 Roussel Uclaf Therapeutic compositions containing derivatives of acrylic acid having an oxygen-containing heterocycle, therapeutic treatment therewith and new compounds
EP0494620A3 (en) * 1991-01-09 1995-06-21 Kanegafuchi Chemical Ind Process for preparing trans-beta-aroylacrylic ester

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2513157A1 (en) * 1974-03-25 1975-10-09 Fabre Sa Pierre AROMATIC KETO ACIDS AND THEIR DERIVATIVES
US4483868A (en) * 1980-04-24 1984-11-20 Roussel Uclaf Gastro-protecting activity
FR2481270A1 (en) * 1980-04-24 1981-10-30 Roussel Uclaf NOVEL SUBSTITUTED DERIVATIVES OF 4-PHENYL 4-OXO 2-HYDROXY BUTANOIC ACID, PROCESS FOR THEIR PREPARATION AND APPLICATIONS AS MEDICAMENTS
DE3116414A1 (en) * 1980-04-24 1982-04-01 Roussel-Uclaf, 75007 Paris "USE OF SUBSTITUTED DERIVATIVES OF 4-PHENYL-4-OXO-2-HYDROXY BUTTERIC ACID AS A MEDICINAL PRODUCT"
US4402978A (en) 1980-04-24 1983-09-06 Roussel-Uclaf Gastro-protecting activity of substituted derivatives of 4-phenyl-4-oxo-2-hydroxy-butanoic acid
DE3214081A1 (en) * 1981-04-17 1982-11-04 Roussel-Uclaf, 75007 Paris USE OF PHENYL ALIPHATIC CARBONIC ACID DERIVATIVES AS A MEDICINAL PRODUCT
US4436752A (en) 1981-04-17 1984-03-13 Roussel Uclaf Treatment of gastric and gastro-duodenal disorders with derivatives of phenyl aliphatic carboxylic acids
US4454155A (en) * 1981-10-22 1984-06-12 Roussel Uclaf Pharmaceutical compositions containing a mono-substituted derivative of 4-phenyl-4-oxobuten-2-oic acid, and methods of using them in treating gastric and gastroduodenal ailments
US4473583A (en) * 1981-10-22 1984-09-25 Roussel Uclaf Compositions containing certain derivatives of 4-phenyl-4-oxobuten-2-oic acid and methods of treatment using them
US4486429A (en) * 1981-10-22 1984-12-04 Roussel Uclaf Amino derivatives of 4-phenyl 4-oxobuten-2-oic acid, pharmaceutical compositions containing them, and methods for preparing and therapeutically using them
US4814348A (en) * 1983-01-24 1989-03-21 Roussel Uclaf Therapeutic compositions containing derivatives of acrylic acid having an oxygen-containing heterocycle, therapeutic treatment therewith and new compounds
US4594443A (en) * 1983-08-25 1986-06-10 Roussel-Uclaf Derivatives of 4-phenyl-4-oxo-buten-2-oic acid and therapeutic use thereof
EP0494620A3 (en) * 1991-01-09 1995-06-21 Kanegafuchi Chemical Ind Process for preparing trans-beta-aroylacrylic ester

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