GB2181732A

GB2181732A - Process for the preparation of 2E 4E carboxylic acids

Info

Publication number: GB2181732A
Application number: GB08624988A
Authority: GB
Inventors: Jozsef Barkoczy; Gyula Kortvelyessy; Jozsef Reiter
Original assignee: Egyt Gyogyszervegyeszeti Gyar; Egis Pharmaceuticals PLC
Current assignee: Egyt Gyogyszervegyeszeti Gyar; Egis Pharmaceuticals PLC
Priority date: 1985-10-18
Filing date: 1986-10-17
Publication date: 1987-04-29
Also published as: ES2002040A6; HUT41725A; IT1197887B; FR2588862A1; DE3635613A1; IT8622043A0; CS754386A2; CS268682B2; DD253994A5; YU176786A; HU200583B; FI864219A; NL8602620A; FI864219A0; JPS62181233A; GB8624988D0; GB2181732B

Abstract

A process for the preparation of 2E,4E carboxylic acids of the general formula <IMAGE> (wherein X stands for hydrogen, hydroxy or C1-4alkoxy) from 2Z,4E carboxylic acids of the general Formula VII <IMAGE> (wherein X is as stated above) comprises isomerizing the 2Z,4E carboxylic acid of the general Formula VII or an alkali metal or ammonium salt thereof, in the melt or in the presence of an inert solvent, in the presence of a catalyst comprising a free electron-pair, and thereafter separating the carboxylic acid of the general Formula I in the form of the ammonium salt thereof without removing the catalyst. The process is readily feasible and there is no need to remove the catalyst. The compounds of the Formula I are known intermediates useful in the preparation of known selective insecticides.

Description

SPECIFICATION Process for the preparation of 2E,4E carboxylic acids This invention relates two a new and improved process for the preparation of carboxylic acids of the general Formula I

having a 2E,4E stereoconfiguration (wherein X stands for hydrogen, hydroxy or CIA alkoxy).

The compounds of the general Formula I are useful intermediates in the preparation of esters of the general Formula II

having a 2Z, 2E,4E stereoconfiguration (wherein Xis as stated above and R stands for a straight or branched chain saturated or unsaturated alkyl group). The esters ofthe general Formula II inhibit the metamorphosis of insects and are highly active selective insecticides being non-detrimental to environment.

In prior art a number of processes are disclosed for the preparation of the compounds of the general Formula I.

A3804-62 MR According to U.K. patent No., 1 ,368,266the compounds ofthe general Formula I (wherein X stands for hydrogen) is prepared from dihydrocitronellal of the Formula Ill

which is condensed with a phosphate anion of the general Formula IV

(wherein R1 and R2 are alkyl) whereupon the mixture of the 2E,4E ester of the general Formula V

and the 2X, 4E ester ofthe general Formula VI

thus obtained (wherein R' is as stated above) is converted into the mixture of the acids ofthe general Formulae land VII

by alkaline hydrolysis (wherein X is hydrogen).According to the said patentthe acids ofthe general Formulae land VII are separated through the corresponding S-benzyl-isothiorunium salts by crystallization. Theyield and melting point of the pure acid ofthe general Formula I are however not disclosed in the said U.K. patent.

The above process is accompanied by several drawbacks. On the one hand the preparation ofthe compound ofthe general Formula IV is complicated while on the otherthe separation of the unsaturated 2E,4E acid ofthe general Formula land the 2Z, 4E acid ofthe general Formula VII is circumstantial and this decreases significantly the yield.

According to a further process disclosed in the said patentthe unsaturated ketone ofthe Formula VIII

is reacted with a carbanion prepared from a phosphonic acid ester of the general Formula IX

(wherein R1 and R2 are as stated above) or with an ilide ofthe general Formula Xwherein R1 and R2 are as stated above, whereupon the mixture of the unsaturated esters of the general Formulae V and VI is hydrolysed into a mixture of the unsaturated acids ofthe general Formulae land VII (wherein X stands for hydrogen).

The disadvantage of the above process resides in theformation of an isomer mixture and the difficult availability of the unsaturated ketone of the general Formula VIII.

According to a further process disclosed in the said patent dihydro-citronellal ofthe Formula lil is condensed with an acetylide of the general Formula Xl CH3-C=C-R3 (Xl) wherein R3 stands for lithium, sodium, potassium or magnesium, whereupon the acetylene derivative ofthe Formula XII

thus obtained is treated with an ortho ester in the presence of a weak acid as catalyst to yield an allene ester of the general Formula XIII

(wherein R' is as stated above), whereupon the said product is converted in alkaline medium to a mixture ofthe esters of the general Formulae V and VI.In the course of the said transformation the stereoconfiguration ofthe C4-C5 double-bond is however partially changed and consequently the compounds of the general Formulae XIV

(2Z,4Z) and XV

(2E, 4Z) are also formed, which makes the isolation of the compounds of the general Formula V still more difficult.

From the esters ofthe general Formulae V and VI the mixture ofthe acids ofthe general Formulae land VII (wherein X is hydrogen) is prepared by hydrolysis.

The disadvantage of the above method is that a multicomponent isomer mixture is formed from which the desired acid of the general Formula I (wherein X is hydrogen) can be isolated but in a complicated manner.

According to UK patent No. 1,368,267 compounds ofthe general Formula I (wherein X stands for hydroxy or alkoxy) are prepared by condensing citronellal ofthe Formula XVI

with a phosphate anion ofthe general Formula IV, (wherein R1 and R2 stand for alkyl), converting the mixture of the 2E,4E ester of the general Formula XVII

and the 2Z, 4E ester of the general Formula XVIII

(wherein R1 is as stated above) into a mixture of the 2E,4E acid of the general Formula XIX

and the 2Z, 4E acid of the general Formula XX

and thereafter additionating water or the corresponding alcohol onto the said acids to yield a mixture ofthe acids of the general Formulae I and VII (wherein Xstandsfor hydroxy or alkoxy) and separating the desired 2E,4E acid of the general Formula I from the said mixture.

According to the other variant of the said process water orthe corresponding alcohol is directly additionated on the mixture of the esters of the general Formulae XVII and XVIII. Thus a mixture ofthe esters of the general Formula XXI

and XXII

is obtained (wherein R3 stands for hydrogen or CiA alkyl and R1 is as stated above) which is subjected to alkaline hydrolysis to yield the mixture of the acids of the general Formulae land VII (wherein X stands for hydroxy or alkoxy).

The drawback of the above process resides on the one hand in the difficult availability of the compounds of the general Formula IV and in the separation ofthe isomeric acids on the other.

According to a further process disclosed in the said patentthe saturated ketone of the Formula XXIII

is reacted with carbanion prepared from a phosphonic acid ester of the general Formula IX or with an ilide of the general Formula X

whereupon the mixture of the esters of the general Formulae XXIV

and XXV

(wherein R1 is as stated above) is hydrolyzed in alkaline medium into a mixture of the acids of the Formulae XIX and XX, on which water or the corresponding alcohol is additionated to yield a mixture of the acids ofthe general Formulae I and VII (wherein X stands for hydroxy or alkoxy).

According to a further variant of the above process water or the corresponding alcohol is additionated on a mixture of the esters of the general Formulae XXIV and XXV, whereupon the mixture of the esters ofthe general Formulae XXI and XXII thus obtained is hydrolyzed in alkaline medium to yield a mixture oftheacidsof the general Formulae land VII (wherein X stands for hydroxy or alkoxy).

The drawback of the above process resides in the formation of the isomeric mixture and the difficult availability ofthe unsaturated ketone of the Formula XXI II.

According to a further method disclosed in the said patent citronellal of the Formula XVI is condensed with an acetylide ofthe general Formula XI (wherein R3 stands for lithium, potassium, sodium or magnesium), whereupon the acetylene derivative of the Formula XXVI

is reacted with an ortho ester is the presence of a weak acid as catalyst, the allene ester ofthe general Formula XXVII

(wherein R1 is as stated above) is treated in alkaline medium to give a mixture of the esters of the general Formulae XVIl and XVI II. In the course of the said treatment however the spatial configuration of the C4-C5 double-bond is partially changed and this gives rise to the formation ofthe esters of the general Formulae XXVI II

and XXIX

too (wherein R1 is as stated above).

From the mixture of the esters ofthe general Formulae XVII and XVIII the mixture of the acids of the general Formulae land XII (wherein Xstandsfor hydroxy oralkoxy) is prepared as described above.

The disadvantage of the above process isthatthe desired compound of the general Formula I (wherein X stands for hydroxy or alkoxy) can be isolated and separated from the above mixture but in a complicated manner.

According to a further process disclosed in the said patent water or the corresponding alcohol is additionated on citronellal of the Formula XVI, whereupon the aldehyde ofthe general Formula XXX

thus obtained (wherein R3 stands for hydrogen or alkyl) is reacted with a phosphonate anion of the general Formula IV and the mixture of the esters of the general Formulae XXI and XXII thus obtained is worked up as described above.

According to a further method water or the corresponding alcohol is additionated on the unsaturated ketone ofthe Formula XIII, whereupon the unsaturated ketone of the general Formula XXXI

thus obtained (wherein R3 is as stated above) is reacted with a carbanion prepared from a phosphonic acid ester of the general Formula IX or with an ilide of the general Formula Xto yield a mixture of the esters ofthe general Formulae XXI and XXII which is worked up as described above.

According to UK patent No. 1,409,321 a ketone of the Formula VIII, XXII I or XXXI is reacted with an organic zinc salt prepared from a halo acetate ofthe general Formula XXXII X-CHTCOOR4 (XXXII) (wherein X is chlorine or bromine and R1 is as stated above), whereupon the hydroxy ester of the general Formula XXXII I

(wherein Za stands for hydrogen or-OR3, R3 is as stated above and Z2 iS hydrogen or Z1 and Z2 together form a double bond) is dehydrated to yield a mixture ofthe esters of the general Formulae V and VI, or XVII orXVlll,or XXI and XXII, respectively, from which the acids of the general Formula I can be prepared along the lines disclosed above.

The disadvantage ofthe above methods resides in the complicated separation of the isomer mixtures and the difficult availability of the ketone starting materials.

According to US patent No. 3,873,586 an aldehyde of the Formula III, XVI or XXX is reacted with a dilithium salt of the general Formulae XXXIVa orXXXIVb

the carboxylic acid of the general Formula XXXV

thus obtained (wherein R4 stands for hydrogen and Za and Z2 have the same meaning as stated above) is subjected to thermal isomerization to yield the hydroxy acids of the general Formulae XXXVla and XXXVlb

(wherein Z1 and Z2 are as stated above and R4 stands for hydrogen), from which a mixture of the acids ofthe general Formulae land VII ora mixture ofthe acids ofthe general Formulae XIX and XXis obtained by dehydration and the compound of the general Formula I is isolated from the said mixtures according to a method described above.

The above method is accompanied by a number of drawbacks. Thus a very Iowtemperature (-80 C) is applied, a lithium salt is to be used and in the course of dehydration the undesired isomers ofthe general FormulaeXXXVII

and XXXVIII

(wherein Z1 and Z2 are as stated above and R4 stands for hydrogen) can also be formed. The separation and isolation of the desired compounds of the general Formula I is therefore complicated and difficult.

According to a further variant of the said patent an aldehyde of the general Formula Ill, XVI or XXX is reacted with an ester lithium salt of the general Formulae XXXIXa orXXXIXb

(wherein R1 stands for alkyl) to yield a hydroxy ester ofthe general Formula XXXV which is worked up as described above.

According to a further variant ofthe above process an aldehyde ofthe general Formula III, VI or XXX is condensed with an ester lithium salt of the general Formula XXXIXa or XXXIXb at -80 C, the reaction mixture is heated to yield in situ a mixture of the hydroxy esters ofthe general Formulae XXXVla and XXXVlb and the lactone ofthe general Formula XL

(wherein Xa and Z2 are as stated above). The mixture is separated by chromatographic methods.The hydroxy esters ofthe general Formulae XXXVla and XXXVlb (wherein R4 stands for alkyl) are worked up and subjected to further reactions as disclosed above, while the lactone ofthe general Formula XL is converted into the salts ofthe hydroxy acids ofthe general Fo rm u lae XXXVla and XXXVlb (wherein Za and Z2 are as stated above and R4 is an alkali metal atom), from which the hydroxy acid of the general Formula XXXVla a n d XXXVlb (wherei n Z and Z2 are as stated above and R4 stands for hydrogen) are obtained by acidification. The acids thus obtained are worked up as described above.

The drawback of the above methods resides in the use of the lithium salts and the separation ofthevarious isomers formed in the reaction.

According to a further process disclosed in the said patent an aldehyde of the Formula III, XVI or XXX is reacted with an acrylic acid ester ofthe general Formula XLI

(wherein Ystandsfor halogen and R1 represents alkyl) in the presence of zinc, whereupon the hydroxy esters of the general Formula XXXVla orXXXVlb are dehydrated to yield a mixture of the esters of the general Formula VandVl, orXVII and XVIII, orXXI and XXII, respectively and the said mixtures are worked up and converted further as described above.

The disadvantage ofthe above method is that the separation ofthe various non-desired isomers formed in the course ofthe allene arrangement is complicated and circumstantial.

According to US patent No.3,911,025 an aldehyde of the general Formula XXX is reacted with an acetylene derivative ofthe general Formula Xl, the hydroxy acetylene derivative of the general Formula XLII

thus obtained (wherein R3 is as stated above) is treated with a trialkyl ortho acetate, the allene ester ofthe general Formula XLIII

thus obtained (wherein R3 is as stated above and R1 stands for alkyl) is re-arranged by means of treatmentwith a sodium hydroxide to yield a mixture of the esters ofthe general Formulae XXI and XXII, whereafterthe said mixture is worked up as described above.

The drawback of the above method resides in the difficult isolation ofthe desired compound of the general Formula I (wherein X stands for hydroxy or alkoxy) and in the lack of stereoselectivity of the re-arrangement.

According to Soviet patent No. 727,624 the unsaturated ketone ofthe Formula VIII or a ketone of the general Formula XXXI (wherein R3 is as stated above) is reacted with the ethoxy-acetylene of the Formula XLIV in the presence of boron trifluoride etherate, whereupon the mixture ofthe esters of the general Formulae II and XLV

thus obtained (wherein X is as stated above and R represents ethyl) is hydrolysed to yield a mixture ofthe acids ofthe general Formulae land Vil.

The patent is silent in disclosing any method for the separation of the isomeric acids of the general Formulae land VII.

According to Soviet patent no. 654,606 ss-hydroxy-dihydro-citronellal of the Formula XLVI

is reacted with a phosphoric acid ester of the general Formula IX, the reaction mixture is acylated with acetic anhydride. Thus a mixture of an ester of the Formula XLVII

and a lactone ofthe Formula XLVI II

is obtained, which is converted first- without separation- into a salt formed with potassium tertiary butylate and then reacted successively with thionyl chloride and an alcohol to yield a mixture of the esters ofthe general Formulae V and VI, which is hydrolysed by means of one ofthe methods disclosed above to yield a mixture of the acids of the general Formulae I and VII (wherein X is hydrogen).There is no disclosure concerning the separation of the mixture.

According to UK patent No. 1,399,196 an aldehyde of the Formula III or XXX is condensed with an ester ofthe general Formula LVII

(wherein R4 stands for alkyl) in alkaline medium whereupon the dicarboxylic acid salt ofthe general Formula XVIII (wherein M stands for alkali) is acidified to give the corresponding dicarboxylic acid of the general Formula LVIII

(wherein X is as stated above and M is hydrogen).

The dicarboxylic acid thus obtained is converted with the aid of a tertiary amine in the presence or absence of copper-ions or copper-wires through a lactone of the general Formula LIX

(wherein X is as stated above) into the corresponding acid of the general Formula VII.

The acid ofthe general Formula VII thus obtained (wherein X is as stated above) is treated in a solvent-free medium with diphenyl-disulfide, thioacetic acid orthiophenol at a lowertemperature in the presence of 2,2-azo-bis-isobutironitrile (radical inducer) or the radical-type reaction is induced at higher temperature to yield a mixture of the acids, wherein the ratio is as follows: I: VII = 60-65:40-35. The radical-type character of the reaction is confirmed in a later publication of the authors [J. Org.Chem. 40,3/19751]. From the reaction mixture the sulfur compounds used by the radical isomerization and the radical introducer are carefully removed in order to avoid any undesired polymerisation reaction, whereupon the mixture of the acids ofthe general Formulae I and VII is dissolved in diethyl ether, dichloro methane, chloroform or hexane,then ammonia is introduced into the solution whereby the ammonium salt ofthe desired acid ofthe general Formula I precipitates in crystalline salt. Thus according to Example 24 of the said patent from 242.5 g of an isomeric mixture 130 g ofthe ammonium salt of the general Formula I (wherein X is methoxy) is obtained and this corresponds to a yield of 50.4%.According to the said patentthe highestyield amounts in principle to 65 %,duetothe equilibrium of cis:trans = 65:35 (thevalueof50.4% referred to above is77.7 ofthesaid equilibrum).

The most serious drawback of this method resides in the isomerization of the acids of the general Formula VII. This reaction is carried out in a solvent-free medium at higher temperature in order to induce radicals or in the presence of a radical-inducer (2,2'-bis-isobutironitrile) which contaminates the reaction mixture. The removal of the agents used in the isomerization ofthe radical inducerwith the aid of Soltrol 130 is particularly disadvantageous because it causes a further destructive thermal load ofthe extremelythermosensitive reaction mixture (e.g. decarboxylation, polymerization, oxidation, splitting oftheterminal XH group maytake place) and this results in a further decrease of the yield.

It is the object of the present invention to overcome the drawbacks ofthe known methods and to provide an improved processforthe preparation of the acids ofthe general Formula I.

It has been found in a surprising mannerthatthe isomerization of the acid ofthe general Formula VII into the acid ofthe general Formula I is not a radical type reaction; moreover it can be accomplished in the presence of hydroquinone as radical trapping agent too. It follows from the above unexpected recognition that no free radicals are needed to induce isomerization but it can be carried out in a solventtoo.

Thus the reaction may be accomplished at a temperature interval between 0 C and 130"C because no thermal induction ofthe radicals is required. The recognition of the non-radical character of the reaction leads to the practical advantagethat not onlythe acids ofthe general Formula VII but the alkali or ammonium salts thereof undergo isomerization as well. For the same reason it is definitely disadvantageous to remove the catalyst from the reaction mixture after isomerization, since from the equilibrum mixture of the acids ofthe general Formulae land VII (I:VII = 60-65::40-35) on separation the ammonium salt of the desired acid ofthe general Formula I precipitates in crystalline form, whereby the ammonium salt of the undesired acid ofthe general Formula VII is enriched in the motherlye and the presence of the catalyst induces further isomerization thereof, thus the yield of the desired acid ofthe general Formula I is increased. A further positive factor is that the reaction mixture is not subjectto thermal treatment to remove the catalyst, consequently no destructive undesired decompositions occur and this further increases the yield.

The present invention is directed to a process for the preparation of 2E,4E carboxylic acids of the general Formula I (wherein X stands for hydrogen, hydroxy or via alkoxy) from 2Z, 4E carboxylic acids the general Formula VII (wherein X is as stated above) by isomerization in the presence of a catalyst which comprises isomerizing a 2Z, 4E carboxylic acid ofthe general Formula VII (wherein X is as stated above) or an alkali metal orammonium saltthereof in the melt or in the presence of an inertsolventin the presence of a catalyst comprising a free electron-pair and thereafter separating from the isomer mixture of the carboxylic acids ofthe general Formulae land VII orthe alkali metal or ammonium saltsthereofthe carboxylic acid ofthe general Formula I in the form of the ammonium saltthereof without removing the catalyst.

A preferred form of realization of the process of the present invention is discussed below.

Isomerization of an acid ofthe general Formula VII (wherein X is as stated above) oran alkali orammonium salt thereof is carried out in the melt or in a suitabie solvent. As solvent e.g. an aliphatic or aromatic hydrocarbon (e.g. petrol, hexane, cyclohexan, benzene,toluene), halogenated hydrocarbon (e.g. dichloro methane, chloro benzene) or an ester or ether (e.g. ethyl acetate, butyl acetate) or a polar solvent (preferably water) may be used.

Isomerization ofthe acid ofthe general Formula VII oran alkali orammonium saltthereofmay be preferably accomplished at a temperature between 00C and 1 300C, preferably at 20-1 000C.

As catalyst comprising a free electron-pair preferably sulfur-containing compounds- particularly thiophenol - may be used.

According to a preferred form of realization of the process of the present invention an acid of the general Formula VII is isomerised in the melt by using thiophenol as catalyst, whereupon the reaction mixture is dissolved in a suitable solvent without removing the catalyst and the desired acid of the general Formula I is precipitated from the solution thus obtained in the form of the ammonium salt by introducing gaseous ammonia.

According to an other preferred form of realization of the process of the present invention isomerization of the acid ofthe general Formula VII is carried out with the aid ofathiophenol catalyst in a solution formed with a suitable solvent, whereupon the acid ofthe general Formula I is precipitated from the solution in form of an ammonium salt by introducing ammonia gas.

According to a still further form of realization of the process of the present invention thiophenol catalyst is added to the solution ofthe ammonium salt an acid ofthe general Formula VII, whereby the ammonium salt ofthe acid ofthe general Formula I is precipitated from the solution.

The process of the present invention shows the following advantages: 1. Since according to our recognition the isomerization is not a reaction of the radical type, it can also be carried out in a solvent as medium.

2. The reaction can be accomplished at lowertemperature too, i.e. at room temperature.

3. Not only the free acid ofthe general Formula VII but a saltthereofcan be used too.

4. There is no need to remove the isomerization catalyst from the reaction mixture.

5. Since the isomerization catalyst is present in the reaction mixture during the complete course ofthe reaction, the ratio of l:VII = 65:35 determined by thethermodynamic equilibrum can be shifted.

6. The ammonium salt ofthedesired acid ofthe general Formula I is precipitated,whilethe ammonium salt ofthe acid ofthe general Formula VII remains in the solution and is further isomerized in the presence of the isomerizing agent.

7. As a result of the aforesaid the theoretical 65 yield of UK patent No. 1,399,196 (in the Examples yields of 50 % are reported) can be increased in principle asfarasto 100% (according to Example 11 ofthepresent patent application the yield amounts to 75%).

Further details of the present invention are to be found in the following Examples without limiting the scope of protection to the said Examples.

Example I Process forthe preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid To 100 g of 11 -methoxy-3,7,1 1 -trimethyl-2Z,4E-dodecadienoic acid 1 g ofthiophenol are added and the mixture is stirred at 1 000C for an hour. The melt thus obtained is cooled and dissolved in 300 my of ether, the solution is saturated with gaseous ammonia and stirred for an hour, whereupon the precipitated ammonium salt is filtered off. The ammonium salt thus obtained is added to a mixture of a solution of 16 g of concentrated sulfuric acid, 63 ml of water and 300 ml oftoluene. The mixture is stirred at 25"C until the ammonium salt goes into solution.The phases are separated, the organic layer is washed three times with 50 ml of water each and the solvent is distilled off. Thus 53 g of the desired compound are obtained, yield 53 %, purity96.8 (gas chromatography).

Example 2 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds as described in Example 1 except that after cooling the melt is dissolved in cyclohexane in the place of ether. Thus 54 g ofthe honeylike desired compound are obtained, yield 54%, purity97 (gas chromatography).

Example 3 Preparation of 11 -hydroxy-3,7, 11 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 1 except that 11 -hydroxy-3,7,1 1 -trimethyl-2Z,4E-dodecadienoic acid is used as starting material and after isomerization the isomers are separated by using dichloro methane in the place of ether. Thus 55 g ofthe honeylike desired compound are obtained, yield 85%, purity97.8 (gas chromatography).

Example4 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 1 except that the melt is dissolved after cooling in toluene in the place of ether. Thus 54 g ofthe desired compound are obtained, yield 54%, purity 96.8 % (gas chromatography).

Example 6 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 4 exceptthatthe reaction mixture is stirred at 300for 3 hours and not for an hour. Thus 61 g ofthe desired compound are obtained, yield 61 %, purity97.2% (gas chromatography).

Example 6 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to ExampleS exceptthat aftercooling the melt is dissolved in ethyl acetate in the place of ether. Thus 60 g of the honeylike desired compound are obtained, yield 60%. Purity97.9 (gas chromatography).

Example 7 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid 100 g of 1 l-methoxy-3,7,1 l-trimethyl-2Z,4E-dodecadienoic acid are dissolved in 300 ml of cyclohexane whereupon 2 g ofthiophenol are added. The reaction mixture is stirred at 200C for a day, the solution thus obtained is saturated with ammonia gas at 25-300C and stirred for a further 5 hours. The precipitated ammonium-1 1 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoate is filtered and worked up as described in Example 1. Thus 67 g of the desired compound are obtained, yield 67 %, purity98.7 (gas chromatography).

Example 8 Preparation of 11 -methoxy-3,7,11 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 7 exceptthat as solvent ethyl acetate is used in the place of cyclohexane. Thus 66 g ofthe honeylike desired compound are obtained, yield 66 %, purity 98.5 % (gas chromatography).

Example 9 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 8 except that in addition to 2 g ofthiophenol 29 of hydroquinone are used. Thus 67 g of the honeylike desired compound are obtained. Yield 67 %, purity 98 % (gas chromatography).

Example 10 Preparation ofl 11 -methoxy-3,7,11 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 7 exceptthat 100 g of 3,7,11-trimethyl-2Z,4E-dodecadienoic acid are used as starting material and isomerisation is carried outat 80"Cfor4 hours. Thus 63 g of the honeylike desired compound are obtained, purity of 97.8% (gas chromatography).

Example 11 Preparation of 1 1-methoxy-3,7,1 1-trimethyl-2E,4E-dodecadienoicacid One proceeds according to Example 7 except that cyclohexane is replaced bytoluene and the reaction is stirred under a slight overpressure of ammonia for 12 hours rather than for 5 hours. Thus 75 g of the honeylike desired compounds are obtained, yield 75 %, purity 99.1 % (gas chromatography).

Example 12 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 7 except that cyclohexane is replaced by toluene and isomerization is carried out at 1 OO"C fo r 2 hours. Thus 63 g of the desired compound are obtained, yield 63%, purity 97.9% (gas chromatography).

Example 13 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 7 except that cyclohexane is replaced by ethyl acetate and isomerization is carried out at 1000 C for 2 hours. Thus 61 g of the desired honeylike compound are obtained, yield 61 %. Purity 98.7 % (gas chromatography).

Example 14 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 7 except that cyclohexane replaced by ethyl acetate. Thus 68 g ofthe desired compound are obtained, yield 68 %, purity 99.3 % (gas chromatography).

Example 15 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 7 exceptthat cyclohexane is replaced by dichloro methane. Thus 64 g of the honeylike desired compound are obtained, yield 64 %r purity 98.3% (gas chromatography).

Example 16 Preparation of 11 -methoxy-3,7,11 -trimethyl-2E,4E-dodecadienoic acid 100 g of 11 -methoxy-3,7,1 1 -trimethyl-2Z,4E-dodecadienoic acid are dissolved in 300 ml of cyclohexane, the solution is saturated with ammonia,5 g ofthe thiophenol are added and the mixture is stirred at 200C for 2 days undera slight ammonia overpressure. The precipitated ammonium salt isfiltered off and further on one proceeds as described in Example 1. Thus 53 g ofthe honeylike desired compound areobtained,yield 53%, purity97.6% (gas chromatography).

Example 17 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 16 except that cyclohexane is replaced by toluene and the isomerization is carried out for 3 days rather than for 2 days. Thus 60 g of the desired compound are obtained, yield 60%, purity 98.2 % (gas chromatography).

Example 18 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 16 except that cyclohexane is replaced by ether. Thus 48 g ofthe honeylike desired compound are obtained, yield 48 %, purity 98 % (gas chromatography).

Example 19 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid One proceeds according to Example 16 except that cyclohexane is replaced by dichloro methane. Thus 47 g of the honeylike desired compound are obtained, yield 47 %, purity97.9% (gas chromatography).

Example 20 Preparation of 11 -methoxy-3,7,1 1 -trimethyl-2E,4E-dodecadienoic acid To a solution of 108.5 g of sodium-i 1-methoxy-3,7,1 1-trimethyl-2Z,4E-dodecadienoate and 300 ml of water 2 g ofthiophenol are added and the reaction mixture is stirred at 20 for a day. The pH is adjusted to 2 by adding 20 % sulfuric acid. The mixture is extracted twice with 150 ml of cyclohexane each, the organic layer is washed three times with 100 ml of water each and the solution is saturated with ammonia. The reaction mixture is worked up as described in Example 7. Thus 56 g ofthe honeylike desired compound are obtained, yield 56%, purity98.4% (gas chromatography).

Claims

1. Processforthe preparation of 2E,4E carboxylic acids of the general Formula I

(wherein X stands for hydrogen, hydroxy or CiA alkoxy) from 2Z,4E carboxylic acids ofthe general Formula VII

(wherein X is as stated above) by isomerization in the presence of a catalyst which comprises isomerizing a 2Z,4E carboxylic acid of the general Formula VII (wherein X is as stated above) or an alkali metal orammonium salt thereof in the melt or in the presence of an inert solvent in the presence of a catalyst comprising a free electron-pair and thereafter separating from the isomer mixture ofthe carboxylic acids of the general Formulae land VII orthe alkali metal orammonium saltsthereofthe carboxylicacid ofthe general Formula I in the form ofthe ammonium saltthereofwithout removing the catalyst.

2. Process according to Claim 1, which comprises carrying out isomerization in an aliphatic or aromatic hydrocarbon, a halogenated hydrocarbon, an ester or an ether.

3. Process according to Claim 2, which comprises carrying out isomerisation intoluene, cyclohexane, dichloro methane, diethyl ether, ethyl acetate orwater.

4. Process according to any of Claims 1 -3, which comprises precipitating the ammonium salt ofthe carboxylic acid or the general Formula I in the same solvent as used in the isomerization reaction.

5. Process according to any of Claims 1-4, which comprises using as catalyst a sulfur-containing compound comprising a free electron-pair.

6. Process according to Claim 5, which comprises using thiophenol as catalyst.

7. Process according to any of Claims 1-6, which comprises carrying out isomerization in the presence of a radical-trapping agent.

8. Process according to Claim 7, which comprises using hydroquinone as radical trapping agent.

9. Process according to any of Claim 1-8, which comprises carrying outthe reaction at atemperature between O"C and 1 OO"C, preferably at 20-1 000C.

10. Process according to Claim 9, which comprises carrying outthe reaction at 20-30"C.

11. Process for preparing a compound of the general formula I where X is as defined in claim 1 su bstantiatly as hereinbefore described in any one of Examples 1 to 20.

12. 2E,4E carboxylic acids of the general formula I, where X is as defined in claim 1, when made bya process as claimed in any one of claims 1 toll.