DE1088951B - Process for the preparation of polyenecarboxylic acids or their esters - Google Patents

Description

GERMAN

kl. 12 ο 25

INTERNAT. KL. C 07 C

PATENT OFFICE

H34804IVb / 12o

REGISTRATION DATE: NOVEMBER 13, 1958

NOTICE
THE REGISTRATION
OND ISSUE OF
EDITORIAL! SEPTEMBER 15, 1960

The present invention relates to a process for the preparation of polyenecarboxylic acids and esters thereof.

The process according to the invention consists in using a phosphonium halide of the formula

Method of manufacture

of polyenecarboxylic acids

or, their esters

XR ₁

I t

(Ar ₇ I) ₃ ^ P-CH-

R,

-CH = C-

-CO O alkyl

(i)

10

where X is a halogen atom, η is the number δ, 1, 2 or 3, R _{1 is} hydrogen or, if η = 0, hydrogen or the methyl group and R ₂ , beginning with the methyl group, alternately denotes the methyl group or hydrogen, in itself converted in a known manner into the corresponding * 5 ^Di P * · phosphorane and this in a manner known per se with an aldehyde of the formula

Applicant:

F. Hoffmann-La Roche & Co.

Corporation,

Basel, Switzerland)

-CH = C-

-CHO

(Π) Representative:

Ing. Dipl.-Chem. Dr. phil. Dr. techn. J. Reltstötter, Patent attorney, Munich 15, Haydnstr. 5

Claimed priority:

Switzerland from November 27, 1957

and Great Britain from August 28, 1958

where the bond shown in dotted lines is optional, R ₃ , beginning with the methyl group, alternately denotes the methyl group or hydrogen and m, if R ₁ in the general formula I denotes the methyl group, represents the number 2, 4 or 6 and, if R ₁ in the general formula I represents hydrogen, represents the number 1, 3 or 5, where the sum of η and m must not exceed the number 6, condensed, triarylphosphine oxide is split off from the adduct formed in the usual way, if desired by heating, if appropriate, the triple bond is partially hydrogenated in a manner known per se, the product obtained is isomerized in a conventional manner and, if desired, the ester obtained is saponified in a manner known per se.

The Phösphoniumhalogenide of the general formula I include, for. B. the following connections:

Carbalkoxymethyltriarylphosphonium halide, a-Carbalkoxyäthyltriarylphosphoniumhalogenid, 3-carbalkoxybutene- (2) -yl- (1) -triarylphosphomum-

halogeriid,
5-carbalkoxy-3-methylpentadien- (2,4) -yl- (l) -triaryl-

phosphonium halide,
7-carbalkoxy-3-methyloctatriene- (2,4,6) -yl- (i) -triarylphosphonium halide.

The triarylphosphonium halides are obtained by condensation of the halogenic acid esters in question, e.g. B. a - haloacetic acid ester, α - halopropionic acid ester, y-halotiglic acid ester, etc., with a triarylphosphine, such as. B. triphenylphosphine, in an inert Dr. Waldemar Guex, Dr. Rudolf Rüegg,

Bottmingen,

Dr. Otto Isler and Dr. Gottlieb Ryser, Basel (Switzerland), have been named as inventors

30 solvents, e.g. B. benzene. The halides required for this are partly new compounds that can be produced as follows:
To a solution of lithium acetylide in liquid ammonia is added a solution of /? - Acetylacrylsäureäthylester in ether and maintaining the reaction mixture refluxed for 1 hour at 30 ⁰ C. The mixture is treated the lithium complex compound by addition of solid ammonium chloride, diluted with ether, can exceed

Evaporate 4-0 ammonia while passing nitrogen through and filter off the solid residues. The ether solution is washed with saturated ammonium chloride solution, dried and the solution is evaporated in vacuo. The syrupy substance obtained is dissolved in ethyl acetate and hydrogenated in the presence of Lindlar catalyst under normal conditions to give 1-carbomethoxy-3-methyl-3-hydroxypentadiene- (1,4); Bp _-003 = 70 to 75 ⁰ C; < ⁸ = 1.4672. By handling the ester with phosphorus tribromide in absolute ether, one obtains the l-carbomethoxy-S-methyl-S-bromopentadiene- (1.3); <= 1.5385.

If, on the other hand, the 1-carbalkoxy-S-methyl-S-hydroxypentadiene- (1,4) with the same amount of dihydropyran and

009 607/425

1 ° / ₀ mineral acid added, one obtains the / S-tetrahydropyranyl ether which is distilled in vacuo after washing the mineral acid with sodium bicarbonate solution and distillation of the excess dihydropyran; Kp _{0, 05} = 85 to 9O ⁰ C. nf = 1.4640. The mixture is hydrogenated in four times the amount of petroleum ether (boiling range 60 to 80 ⁰ C) in the presence of some ChinoHn with Lindlar catalyst to receiving the equimolar amount of hydrogen. By dissolving the ester obtained in eight times the quantity of ether and treated with lithium aluminum hydride at -30 to -20 ⁰ C and working up in the usual manner to give the corresponding primary alcohol which is oxidized by 2stündiges shaking with five times the amount of manganese in petroleum ether to the corresponding aldehyde . The crude product can be purified via the bisulfite addition compound. 4-Methyl-4-tetrahydropyranyloxyhexadiene- (2,5) -al- (1); w | ⁵ = 1.4825; Absorption maxima at 220 ΐημ; E}? "= 670 (in ethanol).

The aldehyde obtained is added to a solution of (α-carbalkoxyethylidene) triphenylphosphorane in methylene chloride and the mixture is heated under reflux for 5 hours. The ester obtained is purified by filtration through five times the amount of weakly active aluminum oxide and, after evaporation of the solvent in vacuo, the ester is obtained as a pale oil; nf = 1.5110; Absorption maximum at 260 πιμ ,; Ei * _m = 870. Dissolve alcohol in twice the amount, can under cooling at 5 ° C 20 ml 63 flow to ° / _o hydrobromic acid, stirred for 2 hours, poured onto ice and taken up in petroleum ether, washed neutral and concentrated at 20 ° C in a vacuum. The 2,6-dimethyl-8-bromooctatriene (2,4,6) acid (I) methyl ester is obtained as a yellow residue; n% = 1.5430; Absorption maximum at 300 ΐημ; Έ \ * 1 = 950 (in petroleum ether).

The aldehydes of the general formula II have a side chain with conjugated multiple bonds throughout. At the point indicated in the formula, the double bond can be replaced by the indicated triple bond. Rer radical R _{3 alternately denotes the methyl group or hydrogen, the radical R 3} closest to the bond, which can be both double and triple, always denotes methyl. For example, if m is the number 3, the aldehyde has the formula

to, while for example the aldehyde at m = 6 corresponds to the following formula:

CHO

(IV)

These aldehydes can be obtained by chain extension of 13- [2,6,6-trimethylcyclohexen- (1) -yl] -2,7,11-trimethyltridecahexaen- (2,4,6,8,10,12) -aIs- (l ) or of 13- [2,6,6-trimethylcyclohexen- (1) -yl] -2,7,11 -trimethyltridecapentaen-(2,6,8,10,12) -in- (4) -as- (l ) can be obtained. For this purpose, the aldehydes mentioned, beginning with the vinyl ether condensation, are used alternately subjected to a vinyl and a propenyl alkyl ether condensation until the desired chain length is reached. Each of these condensations takes place in a manner known per se by acetalization of the aldehyde, Condensation with a vinyl or propenyl alkyl ether and acid treatment of the ether acetal obtained the aldehyde extended by 2 or 3 carbon atoms.

The above-mentioned 13- [2,6,6-trimethylcyclohexen (l) -yl] -2,7,11 -trimethyltridecapentaen (2,6,8,10,12) -in- (4) -al- (l ) is itself a new connection, e.g. B. by organometallic condensation of 10- [2,6,6-trimethylcyclohexen- (1) -yl] -4,8-dimethyldecatriene- (4,6,8) -in- (I) -ol- (3) with 3-isopropoxy-2-methylpropene- (2) -al- (l) and subsequent treatment of the 13- [2,6,6-trimethylcyclohexen- (l) -yl] -2,7, ll-trimethyl-l- isopropoxy-tridecatetraen- (l, 7.9, II) -in- (4) -diols- (3.6) can be obtained with p-toluenesulfonic acid. The required 3-isopropoxy-2-methylpropene (2) -al- (l) is obtained by condensation of ethyl orthoformate with propenyl ethyl ether in the presence of boron trifluoride etherate to give 1,1,3,3-tetraethoxy-2-methylpropane (boiling point bp. _Lo = 93 ° C, <= 1.4132), acid hydrolysis of the latter to free methylmalondialdehyde in aqueous solution and etherification by azeotropic distillation with benzene and isopropyl alcohol in the presence of p-toluenesulfonic acid as a catalyst.

In the first stage of the process according to the invention, a phosphomum halide of the general formula is used converted into the corresponding phosphorane in a manner known per se. For splitting off hydrogen halide from the combination of the general formula if you put the phosphonium salts with organometallic compounds, such as phenyllithium, or alkali alcoholates, z. B. sodium methylate to. The response will be in one

inert solvents such as ether or alcohol, but particularly advantageous in methylene chloride with the exclusion of Oxygen.

According to another embodiment, the phosphonium halides can also be mixed with aqueous alkalis,

z. B. with dilute caustic soda, handily. One obtains z. B. from CarbaJkoxymethyltriphenylphosphoniumhalogenid or from (a-carbalkoxyethyl) triphenylphosphonium bromide the carbalkoxymethylene triphenylphosphorane or the (a-Carbalkoxyäthyliden) triphenylphosphorane as pure crystalline compounds that can be stored without decomposition.

In the second process stage, the phosphorane is condensed in a manner known per se with an aldehyde of the general formula II. It is expedient to use the equivalent amount of the components or an excess of the phosphine compound and work in an inert solvent such as ether, petroleum ether, benzene, methylene chloride, dioxane or tetrahydrofuran. The components are advantageously mixed at room temperature, the supernatant air being expediently replaced by an inert gas such as nitrogen. The use of methylene chloride as a solvent is particularly useful.
The condensation products gradually break down into the polyenecarboxylic acid esters at room temperature

5 6

and the corresponding triarylphosphine oxide. By 10g4,9,13-trimethyl-15- [2,6,6-trimethylcyclohexen- (l) -

Warming up speeds up this reaction. The yl] -pentadecahexaen- (2,4,8,10,12,14) -in- (6) -acid- (1) -me decomposition succeeds z. B. easily by several hours of ethyl ester in 100 ml of petroleum ether (boiling range boiling the methylene chloride solution under reflux. 80 to 105 ⁰ C) with Ig with lead-poisoned palladium

If the ester obtained a triple bond corresponds 5 calcium carbonate catalyst and 0.3 nu quinoline at hold, they can shake the partial hydrogenation and isomerization 20 ⁰ C in a hydrogen atmosphere, whereby tion subject. This takes place in 900 ml of hydrogen per se. The solution known way z. B. by hydrogenation of a suspension is filtered, evaporated in a high vacuum and the back of a triple bond ester in a stand with 50 ml of petroleum ether (boiling range 40 to 45 ° C) inert solvent such as ethyl acetate, toluene shaken io. This gives 8 g of 6,7-mono-cis-4,9,13- or petroleum ether with a lead-poisoned palla-trimethyl-15- [2,6,6-trimethylcyclohexen (1) -yl] pentadium catalyst . If desired, the decaheptaen- (2,4,6,8,10,12,14) acid (1) methyl esters obtained can be obtained as the cis compounds by methods known per se, fine crystal powder; Melting point 103 to 105 ⁰ C ₁ absorption, preferably by heating, to the corresponding maxima at 305 and 424 πιμ, E} * _m = 790 and 1710 all-trans compounds are isomized. Both the 15 (in petroleum ether).

Esters with and without a triple bond can be mixed with 7.5 g of the ice compound with 40 ml of petroleum ether

in a known manner to form the corresponding acids (boiling range 80 to 105 ° C) in a carbonic acid respirator. To this end, the ester is advantageously cooked in a sphere 8 hours under reflux and then inert solvent such as ether, dissolved, and cooled to 0 ⁰ C alcoholic. Orange-red crystals of lischem alkali hydroxide are obtained, preferably with methanoic all-trans ^ .g.lS-trimethyl-IS-P.o.o-trimethylcyclohexene-sodium hydroxide solution, at room temperature under nitrogen- (l) -yl] -pentadecaheptaen- ( 2,4,6,8,10,12,14) acid (1) atmosphere. ethyl ester; Mp. 129 to 130 ° C, absorption maximum

The acids and esters borrowed by the process according to the invention at 426 ΐημ, EJ * _m = 2355 with a secondary maximum at 445 πιμ are crystalline yellow, red or (in petroleum ether). From the mother liquor, through still violet-colored compounds that have been boiled 25 times exceptionally well, a further amount of the product can be obtained, which is much better than that of / 3-carotene and will hold. 1 g of the ester with lycopene is used for saponification. If you store z. For example, the C ₂₇ acid or their 200 ml of 10 ° / ₀ hydrochloric methanoHscher potassium hydroxide solution and 200 ml Methylester or the CGA Säuremethylester open in ether in a nitrogen atmosphere at 2O ⁰ C for 2 days ge-45 ° C, it is observed still stirs after 100 hours. Then the mixture is diluted with water and has a content of 62.7 or 52 or 26 ° / ₀ of effective 3 ° and extracted with ether. The aqueous solution of the acid samer substance. all-trans - /? - Carotene shows under the same is acidified with dilute hydrochloric acid and the pro-storage conditions have a content of 0%, lycopene is filtered off. The all-trans-4,9,13-trimethyl-15- [2,6,6-already after 240 hours such a rate of 0 ° / ₀ . The trimethylcyclohexen- ^ J-ylj-pentadecaheptaen (2,4,6,8, bonds can therefore be used as food coloring, and 10,12,14) acid (l) can be converted from benzene as a poultry feed additive for egg yolk coloring or 35 den; Mp. 186 to 187 ° C, absorption maximum for runs, beaks, skin, fat and meat pigmentation 430 ΐημ, EJ * _m = 2235 (in petroleum ether). be used. The compounds without a triple bond are also effective for vitamin A. Example 2

Particularly valuable dyes are obtained by Kon-. 4 ₎ 9 _{) 1} 3rd _Trimethv i. ₁ 5. _[ 2 ₎ 6,6-trimethylcyclohexen- (l) -yl] -densation of an aldehyde of the aUgemeuien formula II with 40 pentadecahexaen- (2,4,8,10 _J 12,14) -in- (6) - acid- I) -27 carbon atoms to the corresponding ester with methyl ester

thirty consecutive carbon atoms or

by condensation of a 30 carbon atom containing 70g triphenylcarbomethoxymethylphosphonium bromide

aldehydes to the corresponding ester with forty in 1500 ml of cold water are added dropwise with stirring Carbon atoms. 45 wise with dilute caustic soda up to phenolphtha-

a pure alkali reaction. Then the low

Example 1 derschlag filtered off, dried and made of ethyl acetate

all-trans-4,9,13-trimethyl-15- [2,6,6-trimethyl ^{ester under to} S ^a £ ^{e of} petroleum ether umkristaffisiert Man

cyclohexen- (l) -yl] -pentadecaheptaen- receives colorless prisms from carbomethoxymethylene tri-

(2,4,6,8,10,12,14) acid (I) and methyl ester ⁵ ° phenylphosphorane; M.p. 162 to; 163 ° C

53 g of carbomethoxymethylene triphenylphosphorane are

65.6 g of triphenylcarbomethoxymethylphosphonium den in 300 ml of dry methylene chloride in a stick bromide in 300 ml of dry methylene chloride in a substance atmosphere within 5 minutes with stirring a nitrogen atmosphere with stirring with 75 ml with a solution of 44.6 g of 2,7,11-trimethyl-13- [2,6,6-2normal methyl alcoholic sodium methylate solution 55 to trimethylcyclohexen- (l) -yl] -tridecapentaen-(2,6,8,10,12) -placed. After 30 minutes, one in (4) -al- (l) in 300 ml of ethylene chloride is added dropwise in 5 minutes and, as in Solution of 44.6 g of 2,7,1 l-trimethyl-13- [2,6,6-trimethyl- Example 1 described, treated and worked up. Man cyclohexen - ^ - yll-tridecapentaen- (2,6,8,10,12) -in- (4) - receives 48 g ^, lS-trimethyl-lS-p.o.o-trimethylcycloal- (l) in 300 ml of methylene chloride and the mihexen- (1) -yl] -pentadecahexaen- (2,4,8,10,12,14) -in- (6) -mung boils under reflux for 5 hours. It is then filtered, 60 acid (l) methyl ester as orange-red crystals of mp. the methylene chloride solution washed with water and 114 to 116 ° C. after drying over sodium sulfate through a column Example 3

from 200 g of aluminum oxide (activity level I according to.

Brockmann, deactivated with 4% water) filtered. The f -trans-26 1115-tetamethyl-17- [266-t «methyl-

The solution is concentrated and until the start of crystallization 6 ₅ cyclohexen- (1) -yl] -heptadecaoctaen- (2,4,6,8,10,12,14,16) - slowly mixed with methanol. 46.2 g of acid (I) and methyl esters are obtained

4,9,13-trimethyl-15- [2,6,6-trimethylcyclohexen- (l) -yl] - 54 g triphenyl- (a-carbomethoxyethyl) -phosphonium-

Pentadecahexaen- (2,4,8,10,12,14) -in- (6) -acid- (l) -methyl- bromide in 300 ml of dry methylene chloride are in ester as orange crystals; Mp. 114 to 116 ° C, absorption of a nitrogen atmosphere with stirring with 52 ml tion maximum at 407 χημ., EJ * „= 1850 (in petroleum ether). 70 2 normal methyl alcoholic sodium methylate solution

7 8

offset. After 30 minutes, 19.6 g of 47 g of (α-carbomethoxyethylene) triphenylphosphorane are added dropwise in 5 minutes

4,9,13-Trimethyl-15- [2,6,6-trimethylcyclohexen- (l) -yl] - are in 300ml dry methylene chloride in a

Pentadecahexaen- (2,4,8,10,12,14) -in- (6) -al- (1) undergoes 200 ml of nitrogen atmosphere within 5 minutes

Methylene chloride is added and the mixture is boiled with re-stirring with a solution of 19.6 g of 4,9,13-trimethyl-15-flux for 6 hours. It is then filtered and the methylene 5 [2,6 ₎ 6-trimethylcyclohexen- (l) -yl] -pentadecahexaen- [2,4-

chloride solution, as indicated in Example 1, worked up. 8,10,12,14) -in- (6) -al- (l) in 200 ml of methylene chloride

19.8 g of 2,6,1,1,15-tetramethyl-17- [2,6,6-tri-sets and, as described in Example 3, treated and obtained are obtained

methylcyclohexen- (l) -yl] -heptadecaheptaen- (2,4,6,10,12, - worked up. 20.1 g 2,6,11,15-tetramethyl-

14,16) -in- (8)-acid- (l) -methylester as orange-red Kri- ^ -ß.o.ö -trimethylcyclohexen - ^ - yrj-heptadecaheptaenstalle; Mp. 115 to 117 ° C, absorption maximum at io (2,4,6,10,12,14,16) -in- (8) -acid- (l) -methyl ester as orange

423 ma, EjS. == 1950 with secondary maximum at 445 ma red crystals. _. . , _

(in petroleum ether). Example 5

10 g of 2,6,11,15-tetramethyl-17- [2,6,6-trimethylcyclo-afl-traiis ^ Ä13 ^ 7-tetrametbyM9-12A6-trimefltylcycIohexen- (1) -yl] -heptadecaheptaen- (2,4 , 6,10,12,14,16) -in- (8) -hexen-(1) -yl] -nonadecanonaen (2,4,6,8,10,12,14,16,18) -acid - (1) -methyl ester are dissolved in 150 ml petroleum ether (boiling iS “acidic (1) and methyl ester
range 80 to 105 ° C), 0.3 ml of quinoline and 1.5 g with lead 12.4 g of triphenylcarbomethoxymethylphosphonium-poisoned palladium-calcium carbonate catalyst with bromide in 60 ml of dry methylene chloride are shaken at 20 ° C in a hydrogen atmosphere, with the Example 1 described, about 650 ml of hydrogen are taken up with 14.1 ml of 2 normal methyl. In the process, alcoholic sodium methylate solution and 10 g of 2,6,11,15-crystallized the hydrogenation product partially. 20 tetramethyl-17- [2,6,6-trimethylcyclohexen- (l) -yl] -hepta-filtered and the product is separated by dissolving in methylene-decaheptaen- (2,4,6,10,12,14,16) - in- (8) -al- (l) in 60 ml of mechloride and filter off the catalyst. The hydrogenated ethylene chloride is treated and worked up. The solution obtained still contains some starting material and 10 g of 4,8,13,17-tetramethyl-19- [2,6,6-trimethylcyclo- (2,4,6,8,12,14,16,18) induct. The methylene chloride solution is in room 25 (10) acid (l) methyl ester as bronze-colored crystals; temperature in a water jet vacuum and melting point 153 to 154 ° C, absorption maxima at 439 and yields 8 g of 8,9-mono-cis-2,6,11,15-tetramethyl-17- [2,6,6-. 464 ΐημ, Ej ^ = 2110 and 1670 (in petroleum ether).
trimethylcyclohexen- (l) -yl] -heptadecaoctaen- (2,4,6,8,10, - 8 g ^ S.lS. ^ - tetramethyl-WP.oo-trimethylcyclo-12,14,16) -acid- ( l) methyl ester, which by dissolving in hexen- (l) -yl] -nonadecaoctaen- (2,4,6,8,12,14,16,18) -in methylene chloride and adding petroleum ether at 20 ⁰ C 3 ° (lO-acid- (l) -methylester are in 40 ml of toluene, 100 ml can be recrystallized; mp. 131 to 133 ° C, petroleum ether (boiling range 80 to 105 ° C) and 0.3 ml absorption maxima at 324 and 443 ΐημ, Έ \ * _α = 1040 quinoline with 1 g of lead-poisoned palladium-calciumuhd 1780 with secondary maximum at 465 ηΐμ (in petroleum carbonate catalyst at 20 ⁰ C in a hydrogen ether), atmosphere shaken, with about 500 ml of hydrogen

7.4 g of the ice compound will be taken up in 40 ml of petroleum ether 35. The mixture is left overnight

(Boiling range 80 to 105 ° C) stand in a carbonic acid atmosphere at 0 ° C, filtered and separated from the catalyst

Sphere refluxed for 5 hours and then dissolved in methylene chloride, filtering and evaporating the

O ⁰ C cooled. Red crystals of all-trans solvent are obtained. 7.5 g of 10,11-mono-cis-

2,6,11,15-tetramethyl-17- [2,6,6-trimethylcyclohexene- (l) -4,8,13,17-tetramethyl-19 - [2,6,6-trimethylcyclohexenyl] -heptadecaoctaen- ( 2,4,6,8,10,12,14,16) -acid- (l) -me- 40 (1) -yl] -nonadecanonaen- (2,4,6,8,10,12,14,16,18) -acid-

ethyl ester; Mp. 136 to 137 ° C, absorption maxima in (l) methyl ester, which by dissolving in methylene chloride and

445 and 471 πιμ, Ej * _ra = 2575 and 2160 (in petroleum ether). Can be recrystallized by adding petroleum ether;

By boiling the mother liquor again, a melting point of 138 to 140 ° C., absorption maxima at 342 and

further amount of the product can be obtained. 461 πιμ, Ej * _m = 1305 and 1805 with secondary maximum at

For saponification, 1.1 g of the ester in 300 ml of ether 45 481 ΐημ (in petroleum ether).

with 300 ml of 10 ° / ₀ sodium methyl alcoholic potash 2 days 7 g of the cis-compound in 40 ml of petroleum ether

stirred at 20 ⁰ C in a nitrogen atmosphere. Then (boiling range 80 to 105 ⁰ C) in a carbon dioxide atmosphere

the mixture is diluted with water and refluxed with ether sphere for 7 hours. Then there

extracted. The ether solution is filtered and the Nieder- man 70 ml of petroleum ether (boiling range 40 to 45 ° C) and

added shock to the water, with dilute hydrochloric acid 50 left to ^{stand at 0} ° C. overnight. 5 g of all-trans-

acidified and filtered. 0.9 g of all-trans-4,8,13,17-tetramethyl-19- [2,6,6-trimethylcyclohexene-

2,6, ll, 15-tetramethyl-17- [2,6,6-trimethylcyclohexene- (l) - (1) -yl] -nonadecanonaene- (2,4,6,8,10,12,14,16 , 18) -acid-

yl] -heptadecaoctaen- (2,4,6,8,10,12,14,16) acid- (1), the (1) -methyl ester, which is obtained from petroleum ether (boiling range 80 to

can be recrystallized from benzene; Mp. 189 to 105 ° C) can be recrystallized; red-violet crystals,

190 ° C, absorption maximum at 448 ιημ, Ej *, = 2515 55 melting point 145 to 147 ° C, absorption maxima at 464 and

with secondary maximum at 472 ιημ (in petroleum ether). 491 ΐημ, Ej *, = 2570 and 1975 (in petroleum ether). From the

Mother liquors can add more by boiling them again

Example 4 quantities of the product are obtained.

2,6,11,15-Tetramethyl-17- [2,6,6-trimethylcyclo- ^ Jerseiiung 15 g of the ester in 700 ml of ether

hexen- (l) -yl] -heptadecaheptaen- (2,4,6,10,12,14,16) - ⁶ ° ^ ₁ ³ ₊ ⁵⁰ '* J! ^ / o ^^^ ohscher KaLJauge in one

in (8) acid (l) methyl ester in a nitrogen atmosphere at 20 ° C. for 2 days. Then it will be

dilute the mixture with water and add ether extra-

60 g of triphenyl (a-carbomethoxyethyl) phosphonium hiert. The ether solution is nitrated and the precipitate bromide in 1500 ml of cold water are added to the water with stirring, acidified with dilute hydrochloric acid, dropwise with dilute sodium hydroxide solution up to phenol 65 and nitrated. 1.2 g of all-trans-4,8,13,17-tetraphthaleinalkah'schen reaction are obtained. Then the methyl-19- [2,6,6-trimethylcyclohexen- (I) -yl] -nonade precipitate is filtered off, dried and isolated from acetic acid canonaen- (2,4,6,8,10,12,14, 16,18) acid (l), which recrystallizes from benäthylester with the addition of petroleum ether. zol can be recrystallized; Mp. 190 to 191 ⁰ C, almost colorless needles of (a-carbomethoxy absorption maxima at 458 and 495 ΐημ, Ej *, = 2495 ethylidene) triphenylphosphoiane; M.p. 152 to 153 ° C. 70 and 1990 (in petroleum ether).

Example 6

an-trans ^, 6,10,15,19-pentamethyl-21- [2,6,6-trimethylcyclohexen- (l) -yl] -heneicosadecaen- (2,4,6,8,10,12, - 14,16,18,20) acid (l) and methyl esters

21.5 g triphenyl (a-carbomethoxyethyl) phosphonium bromide in 120 ml of dry methylene chloride, as described in Example 3, with 21 ml of 2 normal methyl alcohol Sodium methylate solution and 9.2 g 4,8,13, -17-tetramethyl-19- [2,6,6-trimethylcyclohexen- (1) -yl] - treated nonadecaoctaen- (2,4,6,8,12,14,16,18) -in- (10) -al- (1) in 80 ml of methylene chloride and worked up. Man receives 10 g of copper-colored crystals of 2,6,10,15,19-pentamethyl-21- [2,6,6-trimethylcyclohexen- (1) -yl] -heneicosanonaen- (2,4,6,8,10,14 , 16,18,20) -in- (12) -acid- (1) -methyl ester; Mp. 161 to 163 ° C, absorption maxima at 450 and 479 ΐημ, egg «, = 2320 and 1820 (in petroleum ether).

9.5 g of 2,6,10,15,19-pentamethyl-21- [2,6,6-trimethylcyclohexen- (1) -yl] -heneicosanonaen- (2,4,6,8,10,14,16 , -18.20) -in- (12)-acid- (l) -methyl ester are shaken in 100 ml of toluene with 1 g of lead-poisoned palladium-calcium carbonate catalyst and 0.3 ml of quinoline at 20 ^° C. in a hydrogen atmosphere , whereby about 500 ml of hydrogen are absorbed. 200 ml of petroleum ether (boiling range 40 to 45 ° C.) are added, the mixture is left to stand in the refrigerator for 24 hours, filtered and the catalyst is separated off by dissolving in methylene chloride, filtering and evaporating the solvent. 8 gl ^ lS-mono-cis- ^ ö.lO.lS.lQ-pentamethyl-21 - ß.oo-trimethylcyclohexen- (1) -yl] -heneicosadecaen- (2,4,6,8,10, 12,14,16,18,20) acid (l) methyl ester, which can be recrystallized by dissolving in methylene chloride and adding petroleum ether; gray-violet crystals, m.p. 133 ° C, absorption maxima at 361, 472 and 500 ΐημ, Ε} *, = 1435, 1895 and 1430 (in petroleum ether).

7.5 g of the cis compound are refluxed overnight in 80 ml of petroleum ether (boiling range 80 to 105 ° C.) in a carbonic acid atmosphere and then left to stand at 0 ° C. for 12 hours. 5.5 g of all-trans-2,6,10,15,19-pentamethyl-21- [2,6,6-trimethylcyclohexene - (1) -yl] -henicosadecaen - (2,4,6,8 , 10, -12,14,16,18,20) -acid- (l) -methylester in violet crystals; Melting point 140 to 141 ° C., absorption maxima at 476 and 505 ταμ, EJl = 2630 and 1790 with secondary maximum at 455 πιμ (in petroleum ether). The product can be recrystallized from petroleum ether (boiling range 80 to 105 ° C). A further amount of the product can be obtained from the mother liquor from the isomerization by boiling it again.

In order to hydrolysis 1.5 g of the ester in 700 ml ether and 350 ml of 10 ° / ₀ methanolic potassium hydroxide solution in a nitrogen atmosphere at 2O ⁰ C for 2 days and stirred as indicated in Example 5, worked up. 1.2 g of all-trans-2,6,10,15,19-pentamethyl-21- [2,6,6-trimethylcyclohexen- (1) -yl] -henicosadecaen- (2,4,6,8 , 10,12,14,16, -18,20) acid- (l), which can be recrystallized from benzene; Mp πιμ. 192-193 ° C, absorption maxima at 479 and 507, E ₁ ¹ I = 2500 and 1990 (in petroleum ether).

60 Example 7

aU-trans-4,8,12,17,21-pentamethyl-23- [2,6,6-trimethylcyclohexen (1) -yl] -tricosaundecaen-2,4,6,8,10,12,14 , - 16,18,22) acid (l) and methyl esters

⁶ 5

7.7 g of triphenylcarbomethoxymethylphosphonium bromide in 40 ml of dry methylene chloride are, as described in Example 1, with 8.8 ml of 2 normal methyl alcoholic sodium methylate solution and 7.2 g of 2,6,10, -1 S. ^ - pentamethyl ^ l-pAo-trimethylcyclohexene - ^ - yl] -heneicosanonaen- (2,4,6,8,10,14,16,18,20) -in- (12) -al- (l) treated in 100 ml of methylene chloride and worked up. 7 g of 4,8,12,17,21-pentamethyl-23- [2,6,6-trimethylcyclohexen - (1) - yl] - tricosadecaen - (2,4,6,8,10,12,16 , 18, -20,22) -in- (14)-acid- (I) -methylester in copper-colored crystals; Mp. 181 ΐημ to 182 ⁰ C, absorption maxima at 463 and 492, E} * _m = 2470 and 1870 (in petroleum ether).

5.5 g of 4,8,12,17,21-pentamethyl-23- [2,6,6-trimethylcyclohexen - (1) - yl] - tricosadecaene - (2,4,6,8,10,12,16 , 18, -20,22) -in- (14) -acid- (I) -methylester are in 150 ml of toluene, 0.3 ml of quinoline and 1 g of lead-poisoned palladium-calcium carbonate catalyst in a hydrogen atmosphere Shaken at 20 ° C and, as described in Example 5, worked up. One gets on the whole 4.5 g of 14,15-mono-cis-4,8,12,17,21-pentamethyl-23- [2,6,6-trimethylcyclohexene (1) -yl] -tricosaundecaen- (2,4,6,8,10, -12,14,16,18,20,22) -acid- (l) -methylester, with absorption maxima at 380, 487 and 516 πιμ, Eil = 1175,2100 and 1555, which already turns into the all-trans compound when it is recrystallized. For complete isomerization the product with 100 ml of petroleum ether (boiling range 80 to 105 ° C) for 6 hours in a carbonic acid atmosphere boiled under reflux and, as described in Example 3, worked up. You get the all-trans-4,8,12,17,21-pentamethyl-23- [2,6,6-trimethylcyclohexen (1) -yl] -tricosaundecaen (2,4,6,8,10,12,14 , 16, -18,20,22) -acid- (1) -methyIester as dark purple crystals; Mp. 165 to 166 ° C, with absorption maxima at 488 and 520 πιμ, Eil = 2850 and 2240, with shoulder at 468 ΐημ (in petroleum ether).

For the saponification, 1.1 g of the ester are treated and worked up in 700 ml of ether and 350 ml of 10% strength methanolic potassium hydroxide solution, as indicated in Example 5. The all-trans-4,8,12,17,21-pentamethyl-23- [2,6,6-trimethyl-cyclohexen- (l) -yl] -tricosaundecaen- (2,4,6,8, 10, -12,14,16,18,20,22) acid- (l) as a red, finely crystalline powder which can be recrystallized from toluene; Mp ΐημ. 201 to 203 ⁰ C, with absorption maxima at 492 and 520, egg>"= 2485 and 1925 (in petroleum ether).

Example 8

aU-trans-2,6,10,14,19,23-hexamethyl-25- [2,6,6-trimethylcyclohexen- (l) -yl] -pentacosadodecaen- (2,4,6, -8,10, 12,14,16,18,20,22,24) -acid- (l) and methyl ester

10.7 g triphenyl-ia-carbomethoxyethyl / phosphonium bromide in 60 ml of dry methylene chloride, as described in Example 3, with 10.5 ml of 2 normal methyl alcohol Sodium methylate solution and 5 g 4,8,12,17, -21-pentamethyl-23- [2,6,6-trimethylcyclohexen- (1) -yl] -tricosadecaen- (2,4,6,8,10,12, 16,18,20,22) -in- (14) -al- (l) treated in 60 ml of methylene chloride and worked up. Man receives 4.2 g of 2,6,10,14,19,23-hexamethyl-25- [2,6,6-trimethylcyclohexen- (1) -yl] -pentacosaundecaen- (2,4,6,8,10, -12,14,18,20,22,24) -in- (16) -acid- (l) -methyl ester, which can be recrystallized from toluene petroleum ether; M.p. 187 to 188 ° C, absorption maxima at 473 and 502 πιμ, Eil = 2720 and 2120 with shoulder at 455 πιμ (in petroleum ether).

2.8 g of 2,6,10,14,19,23-hexamethyl-25- [2,6,6-trimethylcyclohexen- (1) -yl] -pentacosaundecaen- (2,4,6,8,10,12 , 14, -18,20,22,24) -in- (16) -acid- (1) -methyl ester are in 100 ml of toluene and 0.3 ml of quinoline. with 1.5 g of lead-poisoned palladium-calcium carbonate catalyst in Shaken in a hydrogen atmosphere at 20 ° C until the hydrogen comes to a standstill. Man the catalyst is filtered off and the toluene is evaporated off in a high vacuum at room temperature. The raw one 16,17-mono-cis-2,6,10,14,19,23-hexamethyl-25- [2,6,6-trimethylcyclohexen (1) -yl] -pentacosadodecaen (2,4,6,8 , 10, -

009 607/425

11 12

12,16,18,20,22,24) - acid - (1) -methylester (absorption ethylate solution and 3 g 4,6,11,15-tetramethyl-17- [2,6,6-tri-

maxima at 392, 495 and 526ΐημ with secondary maximum methylcyclohexen- (l) -yl] -lieptadecaheptaen- (2,4,6,10, -

at 474 ταμ, in petroleum ether) is treated with 100 ml of petroleum ether 12,14,16) -in- (8) -al- (l) in 50 ml of methylene chloride

(Boiling range 80 to 105 ⁰ C) in a carbon dioxide and worked up. Copper-colored crystals are obtained

Sphere boiled overnight, then left to stand at 0 ° C 5 of 4,8,12,17,21-pentamethyl-23- [2,6,6-trimethylcyclo-

and nitrided. The mother liquor is again by hexen- (l) -yl] -tricosadecaen- (2,4,6,8,10,12,16,18,20,22) -in-

Cooking isomerized. A total of 1.7 g of all- (14) -acid- (1) -methyl ester, which with that in Example 7 as

trans -2,6,10,14,19,23 -hexamethyl-25 - [2,6,6 - trimethyl intermediate is the same as the compound described. cyclohexen - (1) - yl] - pentacosadodecaen - (2,4,6,8,10,12, -

14,16,18,20,22,24)-acid- (1) -methylester, which from toluene- io example 12

Petroleum ether can be recrystallized; Mp. 176 _{o ή, "ΛΑ in o",}

up to 177 ⁰ C, absorption maxima at 497 and 529 ΐημ, 2,6,10,14,19 23-hexamethyl-25- [2,6,6-tnmethyl-

EiI = 2950 and 2350 with shoulder at 475 ΐημ (in petrol- ^^^^ Τ ^ Τ ^^ Ψ ^ '}''

... V, ^ ^v 12,14,18,20,22,24) -m- (16) -acid- (l) -methyl ester

For saponification, 1 g of the ester in 700 ml of ether is 15 10 g of phosphomum bromide from 8-bromo-2,6-dimethyl and 350 ml of 10% methanolic potassium hydroxide solution, as in octatriene (2,4,6) acid (l) methyl ester in 100 ml of dry Example 5 described, treated and worked up. Be one _nem methylene chloride, such as beer holds in Example 3, the all-trans-2,6,10,14,19,23-hexamethyl-25- [2,6,6-written with 9 ml of methyl alcohol 2normaler trimethylcyclohexen- (l) -yl] -pentacosadodecaen- (2,4,6,8, - sodium methylate solution and 4g 4,6,11,15,15-tetrame-10,12,14,16,18,20,22,24) - acid - (1) as a dark violet, 20-ethyl-17- [2,6,6-methylcydohexen- (1) -yl] -heptadecafeincrystalline powder, which recrystallizes from toluene heptaen- (2,4,6,10,12,14,16 ) -in- (8) -al- (l) in 50 ml can become methyl; Melting point 210 to 212 ° C., absorption maximum chloride treated and worked up. 2.6 μmum is obtained at 507 μm with a secondary maximum at 535 μm (in 10.14, -19,23-hexamethyl-25- [2,6,6-trimethylcyclohexene petroleum ether). (l) -yl] -pentacosaundecaen- (2,4,6,8,10,12,14,18,20,22,24) -Example 9 25 In (16) -acid- (l) -methylester, of the [compound idencyclohexen- (l) -yl described 2,6,6-trimethyl- ^as intermediate] -pentacosaundecaen- (2,4 in the Examples 2,6,10,14,19,23-hexamethyl-25, 6,8,10,12, - is table.

14,18,20,22,24) -in- (16) -acid- (1) -methylester Example 10

. "" _X ,. ", ... .....,, AE-trans-4,8,12,17,21-pentamethyl-23- [2,6,6-trimethanol-

9 g (a-CarbomethoxyathyhdenJ-tnphenyphosphoran 30 _ογο ι _ο1ιβΧ6η . ₍₁₎ . _Γ1] . _{ΊΓίο05αιιηα60} / _βη . ₍ 2; 4, ₆₎ 8,10,12,14; - (prepared according to Example 4) are in SO ml dry 16,18 20,22)-acid- (l) -methylester
Methylene chloride within 5 minutes with stirring ' ^v ' ^J

with a solution of 5 g 4,8,12,17,21 -pentamethyl- 10 g phosphonium bromide from 6-bromo-4-methylhexa-

23- [2,6,6-trimethylcyclohexen- (l) -yl] -tricosadecaen- (2,4, - dien- (2,4) -acid- (l) -methylester in 100 ml dry

6,8,10,12,16,18,20,22) -in- (14) -al- (l) in 100 ml of methylene 35 methylene chloride are as described in Example 3,

chloride within 5 minutes with stirring mixed with 10 ml of 2 normal methyl alcoholic sodium

and, as described in Example 8, treated and dissolved methylate solution and 2 g of all-trans ^ All ^ S-tetramethyl-

is working. 5.2 g of 2,6,10,14,19,23-hexamethyl-17- [2,6,6-trmethylcyclohexen - ^ - ylJ-heptadecaoctaen-

25- [2,6,6-trimethylcyclohexen- (l) -yl] -pentacosaundecaen- (2,4,6,8,10,12,14,16) -al- (l) in 40 ml of methylene chloride

(2,4,6,8,10,12,14,18,20,22,24) -in- (16) -acid- (1) -methyl- 40 is and worked up. All-trans-4,8,12,17, - is obtained

ester as dark purple crystals. 21 - Pentamethyl-23 - [2,6,6 -trimethylcyclohexen- (1) -yl] -

tricosaundecaen- (2,4,6,8,10,12,14,16,18,20,22) -acid- (I) -

Example 10 methyl ester similar to that described in Example 7

^ o.ll.lS-tetramethyl - ^ - PAO-trimethylcyclohexen- connection is identical.

(l) -yl] -heptadecaheptaen- (2,4,6,10,12,14,16) -in- (8) -acid- ⁴⁵ Example 14

(l) methyl ester

_no τ «. r. ■ ^ -λ -c. Ν ·· χι, ι all-trans-2,6,10,14,19,23-hexamethyl-25- [2,6,6-tri-

36gPhosphonmmbromidausy-Bromtigl_insauremethyl- _me thylcyclohexen- (l) -yl] -pentacosadodecaen- (2,4,6,8, -

esters m 150 ml of dry methylene chloride are like 10,12,14,16,18,20,22 24)-acid- (l) -methylester

described in Example 1, with 37.5 ml of 2 normal methyl 5 °

alcoholic sodium methylate solution and 22.3 g 2.7, 11-4.5 g of phosphonium bromide from 8-bromo-2,6-dimethyl-trimethyl-IS-ß.oo-trimethylcyclohexen - ^ - ylJ-trideoctatriene- (2,4, 6) -acid- (l) -methylesterin 50 ml of dry capentaen- (2,6,8,10,12) -in- (4) -al- (l) in 150 ml of methylene-methylene chloride, as in example 3 described, treated with chloride, worked up and the product purified by recrystallization from petroleum ether with 4 ml of 2 normal methyl alcoholic sodium (boiling range 80 to 55 methylate solution and 2 g of all-trans ^ .o.ll.lS-tetramethyl-105 ⁰ C). Orange crystals of 17- [2,6,6-trimethylcyclohexen- (1) -yl] -neptadecaoctaene-2,6,11,15-tetramethyl-17 - [2,6,6-trimethylcyclohexene- (2,4 , 6,8,10,12,14,16) -al- (l) in 30 ml of methylene chloride be (l) -yl] -heptadecaheptaen- (2,4,6,10,12,14,16) - in (8) acid trades and worked up. All-trans-2,6,10,14, - (l) -methyl ester is obtained, which is the same as that described in Example 3 as an intermediate W ^ S-hexamethyl ^ SP.oo-trimethylcyclohexen ^ J-yl] product Connection is identical. 60 pentacosadodecaen- (2,4,6,8,10,12,14,16,18,20,22,24) -acid-

(l) methyl ester ,. the one described in Example 8

Example 11 connection is identical.

4,8,12,17,21-pentamethyl-23- [2,6,6-trimethyl- _R. . , _ις

cyclohexen- (l) -yl] -tricosadecaen- (2,4,6,8,10,12,16,18, - eispiei 10

20,22) -in- (14)-acid- (l) -methylester ^6s 2,6,10,15,19-pentamethyl-21- [2,6,6-trimethyl-

., ".. ,,,,, τ,,,." Cyclohexene (l) -yl] -heneicosanonaen- (2,4,6,8,10,14 -

10 g of phosphonium bromide from 6-bromo-4-methylhexa-16,18,20) -in- (12)-acid- (l) -ethyl ester
diene (2,4) acid (l) methyl ester m 100 ml dry ' ^K ' ^x ' ^y
Methylene chloride is, as described in Example 3, 10 g of phosphonium bromide from 8-bromo-2,6-dimethyl with 10 ml of 2 normal methyl alcoholic sodium methyl 70 octatriene (2,4,6) acid (l) ethyl ester in 100 ml of dry

Methylene chloride are, as described in Example 3, with 9 ml of 2 normal methyl alcoholic sodium methylate solution and 6g 2,7,11-trimethyl-13- [2,6,6-trimethylcydohexen- (l) -yl] -tridecapentaen- (2,6,8,10,12) -in- (4) -al- (l) treated in 50 ml of methylene chloride and worked up. 2,6,10,15,19-pentamethyl-21- [2,6,6-trimethylcyclohexene is obtained - (1) - yl] - heneicosanonaen - (2,4,6,8, -10,14,16,18,20) -in- (12)-acid- (1) -ethyl ester; Mp. 165 to 166 ° C, absorption maxima at 450 and 478 τημ, 1 = 2275 and 1695.

Claims (3)

Patent claims: 1. Process for the preparation of polyenecarboxylic acids or their esters, characterized in that a phosphonium halide of the formula XR ₁ ^ P —CH- • CH. = (I)
COO alkyl where X is a halogen atom, η is the number 0, 1, 2 or 3, R _{1 is} hydrogen or, if w = 0, is hydrogen or the methyl group and R ₂ , beginning with the methyl group, is alternately the methyl group or hydrogen, in itself converted into the corresponding phosphorane in a known manner and this in a manner known per se with an aldehyde of the formula -CH = C is tative, R ₃ , beginning with the methyl group, alternately denotes the methyl group or hydrogen and m, if R ₁ in the general formula I represents the methyl group, represents the number 2, 4 or 6 and, if R ₁ in the general formula I represents hydrogen, the number 1, 3 or 5, where the sum of η and m must not exceed the number 6, condenses, triarylphosphine oxide, cleaved from the adduct formed in the usual way, if desired by heating, optionally the triple bond in partially hydrogenated in a known manner, the reaction product obtained isomerized in the customary manner, and the ester obtained, if desired, saponified in a manner known per se. 2. The method according to claim 1, characterized in that there is triphenyl as the phosphonium halide - (α - carboalkoxyethyl) - phosphonium bromide or triphenyl-P ^ -dimethyl ^ -carbalkoxyheptatriene- (2,4,6) -yl- (l)] - phosphonium bromide and as aldehyde 4,9,13 - trimethyl - 15 - [2,6,6 - trimethylcyclohexen- (l) -yl] -pentadecahexaen- (2,4,8,10,12,14) -in- (6) -Alles) or 2,6, ll, 15-tetramethyl-17- [2,6,6-trimethylcyclohexen- (l) -yl] -heptadecaheptaen- (2,4,6,10,12,14,16) in ( 8) -al- (l) used. 3. Process according to Claims 1 and 2, characterized in that the phosphonium halide is used by treatment with aqueous alkali or with alkali metal alcoholates in the presence of methylene chloride converted as a solvent into the corresponding phosphorane. Considered publications:
German Patent Nos. 950 552, 951 212, 035 647;
Fette, Seifen, Anstrichmittel, Vol. 56, 1954, pp. 986 bis 989;
where the dotted line is facultative Angew. Chemie, Vol. 68, 1956, pp. 547-553. © 009 607/425 9.