DEH0024418MA - - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

Date of registration: July 15, 1955 Made on October 11, 1956

GERMAN PATENT OFFICE

PATENT APPLICATION

CLASS 12 ο GROUP 25 INTERNAT. CLASS C 07c

H 24418 IVb / 12 ο

Dr. Otto Isler, Dr. Marc Montavon, Rudolf Rüegg, Basel, and Paul Zeller, Neuallschwil (Switzerland)

have been named as inventors

F. Hoffmann-La Roche & Co. Aktiengesellschaft, Basel (Switzerland)

Representative: Dr. G. Schmitt, lawyer, Lörrach (Bad.)

Process for the production of retro-dehydropolyene aldehydes

The priority of the application in Switzerland from August 16, 1954 has been claimed

The process according to the invention is characterized in that an aldehyde of the formula

CH ₃ CH ₃

-CH ₀ -CH = CX

CH ₃

X = -CHO ₁ -CH = CH-CHO or -CH = CH-CH = C-CHO

^1st ■ ■■ CH,

whose aldehyde group can be acetalized in the presence of methylene chloride at 0 to 30 ° in an known way of a Wohl-Ziegler reaction (cf. C. Djerassi, Chem. Reviews, Vol. 43, 1948, P. 271) and the halogen compound formed is usually heated with a tertiary base, whereby with allyl rearrangement, hydrogen halide is split off.

The aldehydes used as starting materials are produced as follows:

4- [2 ', 6', 6'-Trimethylcyclohexen- (i ') - yl- (i')] - 2-methylbutene- (2) -al- (i): By glycidate synthesis of / S-ionone and ethyl chloroacetate and subsequent Treatment of the glycidic ester with alkali.

609 657/484

H 24418 IVb / 12 ο

6- [2 ', 6', 6'-Trimethylcyclohexen- (i ') - yl- (i')] - 4- ^me thylhexadien- (2, 4) -AL- (i): 4- [2 ', 6 ', o'-Trimethylcyclohexen- (i') - yl- (i ')] - 2-methylbutene- (2) -al- (i) is acetalized with ethyl orthoformate in the presence of a little p-toluenesulfonic acid. The resulting diethyl acetal is then condensed with ethyl vinyl ether in the presence of zinc chloride. The obtained 6- [2 ', 6', 6'-trimethylcyclohexen- (i ') - yl- (i')] - 4-methylhexene (4) -ether- (3) -acetal- (i) is with Acetic acid and sodium acetate heated to 100 °, which causes hydrolysis and elimination of alcohol.

8- [2 ', 6', 6'-trimethylcyclohexen- (i ') - yl- (i')] - 2, 6-dimethyloctatriene- (2, 4, 6) -al- (i): 6- [2 ', 6', 6'-trimethyl-

cyclohexen- (1 ') - yl- (i')] - 4-methylhexadiene- (2, 4) -al- (i) is acetalized with ethyl orthoformate in the presence of a little p-toluenesulfonic acid. The resulting diethyl acetal is then in the presence of Zinc chloride condensed with ethyl propenyl ether. The obtained 8- [2 ', 6', 6'-trimethylcyclohexen- (i ') - yl- (i')] - 2, 6-dimethyloctadiene- (4, 6) -ether- (3) -acetal- (i). will warmed to 100 ° with acetic acid and sodium acetate, resulting in hydrolysis and elimination of alcohol be effected. . ■>

The acetals are prepared from the aldehydes nach'be- ^one knew methods, for example ^ with Orthoameisensäureester.

The first stage of the process according to the invention consists in the halogenation of the starting aldehyde or acetal on the methylene group of the side chain. · The halogenation takes place in a manner known per se according to the reaction of Wohl and Ziegler. Preferably is applied for this purpose, N-bromosuccinimide or N-bromoacetamide in methylene chloride at a temperature between 0 and 30 ^{the 0th} The halogenating agent is suitably used in an approximately io ° / ₀ by weight excess. The reaction can be accelerated by adding catalysts, such as dibenzoyl peroxide, or by exposure to light.

When working with N-bromosuccinimide, sodium bicarbonate is expediently added to the reaction mixture and calcium oxide too. . After the reaction has ended, this takes 15 minutes, depending on the temperature used takes up to 4 hours, is filtered and the solvent, if desired, removed in vacuo.

The halogen compounds obtained, which should have the following formula,
CH ₃ CH ₃

i CH ^ CH = C ^

CH,

■ CH,

X has the meaning given above. ^J are not very stable and darken when stored. They are expediently processed immediately without cleaning.

The second stage of the procedure consists of the usual Elimination of hydrogen halide with allyl rearrangement. It is done by adding an excess a tertiary base such as quinoline, pyridine, dimethylaniline, or Collidifi, while heating the mixture. The reaction mixture is preferably heated with quinoline for 2 to 6 hours in a nitrogen atmosphere to ioo °.

The reaction mixture is expediently worked up by adding ice-cold excess dilute acid and extraction of the product with an organic solvent, for example petroleum ether.

In the acidic work-up, acetal groups can be saponified in whole or in part. . .

The products of the general formula obtained

CH,

CH-CH = CX
CH,

Phenylsemicarbazones of Aldehydes

X hat.die meaning given above, are used in the usual way, e.g. B. by distillation, crystallization or chromatography, purified. They have characteristic absorption maxima in the ultraviolet spectrum. Because of the cis-trans isomerism at the double bonds, there are different spatial shapes these aldehydes or acetals,. for 6- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene- (i')] - 4-methylhexadiene- (2,4) -al- (i) two different phenylsemicarbazones can be isolated. The following table contains an overview of the phenylsemicarbazones corresponding to the aldehydes that can be prepared according to the invention:

U V. absorption maxima
, in petroleum ether

λ max. πιμ

Egg*

"[2 ', 6', 6'-Trimethylcyclohexen- (2 ') - yliden- (i')] - 2-methylbutene- (2nd) - al- (i) (retrodehydro-C ₁₄ -aldehyde) '. /.

[2 ', 6', 6'-trimethyl-cyclohexen- (2 ') - yliden- (i')] -4-methylhexadiene- (2, 4) -al- (i) (retrodehydro-cig-aldehyde)

- [2 ', 6', 6'-Trimethyl-cyclohexen- (2 ') - yliden- (i')] - 2, 6-dimethyloctatriene- (2, 4, 6) -aJ- (i) (retrodehydro- C ₁₈ aldehyde)

160 to 161

a) 184 to 186

b) 164 to 166

198 to 201

339; 354

366; 386
362; 382

372.5; 393; 4Ϊ6.5

1870; 1590

2330; 2160
2140; r8oo

1690; 2575: 2360

609,657 / 484

H 24418 IVb / 12 ο

The aldehydes or their acetals which can be prepared according to the invention are important intermediate products for the production of carotenoids, such as 4, 4'-dioxycarotene and bisdehydro-ß-carotene, dar; 'the 4- [2', 6 ', 6'-Trimethylcyclohexen- (2') -yliden- (i ')] - 2-methylbutene- (2) -al- (i) and its acetals have fragrance properties and can therefore be used as components be used in odoriferous mixtures. The 6- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene- (i')] -4-methylhexadiene- (2, 4) -al- (i) can be converted into the 8- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene- (i')] - 2, 6-dimethyloctatriene- (2, 4, 6) -al- (i) convert as follows: means Ethyl orthoformate is acetalized in the presence of a little p-toluenesulfonic acid; the resulting Diethylacetal is then condensed with ethyl propenyl ether in the presence of zinc chloride; that obtained 8- [2 ', 6', 6'-trimethylcyclohexen- (2 ') -ylidene- (i')] -2,6-dimethyloctadiene- (4, 6) -ether- (3) -acetal- (i ) is heated to 100 ° with acetic acid and sodium acetate, with hydrolysis and cleavage of alcohol 8- [2 ', 6', 6-trimethylcyclohexen- (2) ylidene- (i ')] - 2, 6-dimethyloctatriene- (2, 4, 6) -al- (i) is formed.

Das4 "[2 ', 6', 6'-Trimethylcyclohexen- (2 ') - ylidene- (i')] - 2-methylbutene- (2) -al- (i) in the same reaction sequence using ethyl vinyl ether instead of ethyl propenyl ether gives 6- [2 ', 6', 6'-trimethylcyclohexene (2 ') - ylidene- (i')] - 4-methylhexadiene- (2,4) -al- (i).

Protection is not sought for the production of the starting materials in the context of the present invention.

example 1

30 parts by weight of 4- [2 ', 6', o'-trimethylcyclohexen- (i ') - yl- (i')] - 2-methylbutene- (2) -al- (i) in 210 parts by weight of methylene chloride are mixed with 13, 5 parts by weight of sodium bicarbonate and 9 parts by weight of calcium oxide cooled to 0 ° with stirring. Then 28 parts by weight of N-bromosuccinimide are added and the temperature is maintained for 3 hours by occasional cooling to 5 to 10 °. The mixture turns yellow to red after a while and slowly becomes colorless again. It is then filtered, 30 parts by weight of quinoline are added and the methylene chloride is removed in vacuo. A further 30 parts by weight of quinoline are then added and the mixture is heated on the steam bath under nitrogen for 2 hours. 350 parts by weight of petroleum ether (boiling point 30 to 60 °) are then added to the mixture and it is poured, with stirring, onto 250 parts by weight of 3 η-sulfuric acid and ice. The insoluble resin is filtered off, the aqueous layer is separated off and the petroleum ether solution is washed once with water, dilute sodium bicarbonate solution and water. After the petroleum ether solution has been dried over sodium sulfate and evaporated, 29.4 parts by weight of crude 4- [2, 6 ', δ'-trimethylcyclohexen- (2') -yliden- (1 ')] -2-methylbutene- (2) -al are obtained - (i) obtained; For purification, this product is distilled in a Hickmann flask under a high vacuum; Boiling point 9070.03 mm. A completely pure product is obtained if the compound is still distilled through a Vigreux column (30 cm). The aldehyde forms a yellow, thin oil, nf = 1.6152; UV absorption maximum at 318 rriji ES, = 1610 (in petroleum ether). ': ^; M.

Example 2

34 parts by weight of 6- [2 ', 6', δ'-trimethylcyclohexen- ■ (i ') - yl- (i')] - 4-methylhexadiene- (2,4) -al- (i) become in 210 parts by weight of methylene chloride 13.5 parts by weight of sodium bicarbonate, 9 parts by weight calcium oxide and 28 parts by weight of N-bromosuccinimide as indicated in example 1, treated with the bromination ^r ι contrast to example 20 is bis.25 °. This gives 19 parts by weight of a crude product, the (deactivated with 2 ° / ₀ water) by chromatography on alumina 3ofachen amount with petroleum ether and a petroleum ether-ether mixture is purified. The 6- [2 ', 6', 6'-trimethylcyclohexen- (2 ') -yliden- (i')] -4-methylhexadiene- (2, 4) -al- (i) obtained is a mixture of isomers. By crystallization from petroleum ether at - 70 ⁰ a shape can be obtained in yellow prisms; Melting point 73 to 74 °, UV absorption maxima at 353 ΐημ, ES, = 2360; 372 ΐημ, ES, 2200 (in petroleum ether). The oily isomer can be partially converted into the crystalline isomer by heating to 100 ° for five hours with acetic acid and sodium acetate; by treating the mother liquors several times, almost the whole amount can be obtained as a crystalline isomer.

Example 3

40 parts by weight of 8- [2 ', 6', 6'-trimethylcyclohexen- (i ') - yl- (i')] - 2, 6-dimethyloctatriene- (2, 4, 6) -al- (i) are in 210 parts by weight methylene chloride 13.5 parts by weight of sodium bicarbonate, 9 parts by weight calcium oxide and 28 parts by weight of N-bromosuccinimide as stated in example 1-treated, wherein the bromination is, in contrast to example 1, 25 to 30 ^0th 22 parts by weight of a crude product are obtained, which is purified by chromatography. The obtained 8- [2 ', 6', 6'-Trimethylcyclqhexen- (2 ') - yliden- (i')] - 2, 6-dimethyloctatrien- (2,4, 6) -al- (i) shows im UV absorption spectrum 2 maxima: 382 πιμ, ES, = 1615 and 403 ΐημ, ES, = 1445-

Example 4

20.5 parts by weight 4- [2 ', 6', 6'-trimethylcyclohexen- (i ') - yl- (i')] - 2-methyl-i, i-diethoxybutene- (i) in 105 parts by weight Methylene chloride is added with 6.75 parts by weight sodium bicarbonate and 4.5 parts by weight Calcium oxide cooled to 0 ° while stirring. 14 parts by weight of N-bromosuccinimide are then added and proceed as described in Example 1. The crude product becomes complete before distillation Saponification of the acetal with 150 parts by weight of glacial acetic acid, 15 parts by weight of sodium acetate and 7 parts by weight Water heated on the steam bath for 3 hours. The mixture is then diluted with 1000 parts by weight of water and extracted with petroleum ether and washes the petroleum ether layer with dilute sodium bicarbonate solution and water. To drying the petroleum ether solution over sodium sulfate and evaporation leaves 29.1 parts by weight

609.657 / 484

H 24418 IVb / 12 ο

raw 4 -D ² '. 6 ', 6' - trimethylcyclohexen - (2 ') - ylidene- (i')] - 2-methylbutene- (2) -al- (i).

Claims (3)

Patent claims: ι. Process for the production of retrodehydropolyenaldehydes, characterized in that one an aldehyde of the formula C Ho V-CH ₂ -CH = CX LcH ' X = - CHO, -CH = CH-CHO or -CH = CH-CH = C-CHO CH, the aldehyde group of which can be acetalized, subjected to a Wohl-Ziegler reaction in a manner known per se in the presence of methylene chloride at 0 to 30 ⁰ and the halogen compound formed is heated in the usual way with a tertiary base such as quinoline, with hydrogen halide being split off with allyl rearrangement. 2. The method according to claim 1, characterized in that that the starting aldehyde is 4 - [2 ', 6', 6 '- trimethylcyclohexen - (1') - yl - (1 ')] - 2-methylbutene- (2) -al- (i) used. 3. The method according to claim 1 and 2, characterized in that the starting aldehyde halogenated by means of N-bromosuccinimide or N-bromoacetamide. Considered publications:
Chem. Rev., Vol. 43, 1948, pp. 271 ff;
German Patent Nos. 818 941 and 839 496; Dear. Ann. d. Chem., Vol. 594, 1955, pp. 165-176.