DE2357752A1 - Trans-3-methyl-2-butene-1,4-dial 1-acetals prepn. - by selenium dioxide oxidation of 3-methyl-2-buten-1-al acetals - Google Patents

Abstract

trans-3-Methyl-2-butene-1,4-dial 1-acetals of formula (I) (where R1-R6 are H or 1-4C alkyl, pref. CH3) e.g. 3-methyl-2-butene-1,4-dial 1-(1,3-propylene)-acetal, are prepd. by oxidising a 3-methyl-2-buten-1-al acetal of formula (II) with selenium dioxide in an ether of b.pt. 70-170 degrees C, benzene, an inert alkyl-substd. or halogenated monocyclic aromatic hydrocarbon or a polychlorinated aliphatic hydrocarbon of b.pt. 70-170 degrees C, pref. at 80-120 degrees C for 5-15 mins. using an approximately equimolar amount of selenium dioxide. (I) are useful as intermediates for carotenoids. Thus, Wittig reaction with beta-ionylidene-ethyl-triphenylphosphonium chloride followed by acidic hydrolysis gives retinal, which has vitamin A activity and is also useful as an intermediate for beta-carotene.

Description

BASF Aktiengesellschaft

Our reference: O. Z. "30 220 Rr / Ri 6700 Ludwigshafen, 19.II.1973

Process for the preparation of cyclic trans-3 ~ methyl-2-butene

-1,4-dial-1-acetals

The invention relates to a method for producing the as Intermediate products for the production of carotenoids *! extremely interesting 1-acetals of 3-methyl-2-butene-l, 4-dial with aliphatic 1,3-diols by oxidation of the corresponding 3-methyl 2-butene-l-al-l-acetals with selenium dioxide in certain solvents.

By Makin et al (J. allg. Chem. (USSR) 32. (1962), page IO9I (Engl.)) It is known that the dietary hylacetal of ^ -Bromo-β-. methyl-crotonaldehyde by reacting with the potassium salt of nitrocyclohexane into 3-methyl-2-butene-1,4-dial-1-diethylacetal (called 4,4-diethoxy-2-methyl-2-buten-1-al ) can transfer. The yields of 3-methyl-2-butene-l, ⁱ J-dial-l-diethylacetal in this. However, processes are only 29 % of theory.

Trans-3-methyl-2-butene-l, 4-dial-l-acetals are available as intermediates of extraordinary interest for the production of carotenoids. It was therefore the object of the invention to provide a method to develop after the 3-methyl-2-butene-l, 4-dial-l-acetals in good yields can be produced.

It has now been found that trans-3-methyl-2-butene-1,4-dial-lacetale of the general formula I.

C-O

\ Ϊ ^Η 3

in which R ¹ to R are hydrogen or an alkyl group having 1 to C atoms, preferably a methyl group, can be produced in a simple manner and with good yields by a

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3-methyl-2-butene-1-al-acetal of the general formula II

2 1

it n

ν / ν /

R ³ / \ CH,
^κ ^ / \, 3

C 'CH-CH = C-CH, (II), ■

R ⁴ C-O
»Ο

in the R to R have the meaning given above, in an ether with a boiling point between 70 and 170 C, benzene, a alkyl substituted or halogenated monocyclic aromatic Hydrocarbon or a polychlorinated aliphatic hydrocarbon with a boiling point between 70 and 170 C as a solvent oxidized with selenium oxide.

It was very surprising that trans-3-methyl-2-butene-1,4-dial-lacetale of the formula I can be prepared by Selendioxidoxy.dation of the corresponding 3-methyl-2-buten-1-al-acetals, since this oxidation produces water, which partially reacts with selenium dioxide to form the strongly acidic selenium acid and it it is known to every person skilled in the art that acetals are easily split into the corresponding aldehydes and alcohols in an aqueous acidic medium (cf. e.g. Houben-Weyl "Methods of Organic Chemistry", Volume 7/1, page 423) and furthermore with an acid-catalyzed Acetalization was to be expected.

It is also known that acetals of o ^ jß-unsaturated aldehydes suffer this acid-catalyzed hydrolysis particularly quickly. For example, from Patai "The Chemistry of functional groups", Interscience Publishers 1967, page 333, Table 3 shows that the hydrolysis constant of the oC, ß-unsaturated crotonaldehyde is about 3 powers of ten greater than that of saturated acetaldehyde. Selenium oxide oxidations of compounds called acetals O (jβ-unsaturated aldehydes contain as structural element has not yet been described.

The analogous production of 1-acetals of the trans-3 ~ methyl-2-butene -1,4-dials with alkanols or ethylene glycol through selenium dioxide

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oxidation of the corresponding 3-methyl-2-butene-1-al-acetals or but the production of 1-acetals of the isomeric 2-methyl-2- -butene-1-al-acetals by selenium dioxide do not succeed.

As 3-methyl-2-butene-l-al-acetals of the formula II, which are based on this way to the corresponding trans-3-methyl.-2-butene-l, 4- Let -dial-1-acetals oxidize, are for example:

3-methyl-2-buten-l-al- (1 ', 3'-propylene) -acetal 3-methyl-2-buten-l-al- (2 ^!, 2 ^f -dimethyl-1', 3'- propylene) acetal 3-methyl-2-buten-1-al- (2 ', 4'-pentylene) acetal

You can easily choose from 3-methyl-2-butenal and the concerned 1,3-diols by boiling in solvents such as benzene, Chloroform or toluene can be produced with the removal of water. Suitable catalysts for this acetalization are for example p-toluenesulfonic acid or phosphoric acid.

As a solvent for the selenium dioxide oxidation according to the invention is being brought up for consideration:

a) Higher-boiling ethers, ie cyclic or acyclic ethers with a boiling point between 70 and 170 ^° C. Cyclic ethers such as 1,4-dioxane, 1,3-dioxane and tetrahydrofuran, and acyclic ethers such as diglycol dimethyl ether and glycol dimethyl ether may be mentioned, for example.

b) Benzene and alkyl substituted monocyclic aromatic Hydrocarbons such as toluene and xylene.

c) Halogenated monoayclic aromatic hydrocarbons, such as Chlorobenzene, bromobenzene and m-dichlorobenzene.

d) Polychlorinated aliphatic hydrocarbons with a boiling point between 70 and 170 C,
chlorethylene and trichlorethylene.

Boiling point between 70 and 170 ⁰ C, such as tetrachloroethane, tetra

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In other solvents otherwise customary for selenium dioxide oxidations, such as ethanol, tert-butanol or glacial acetic acid, the compounds of the formula I were only obtained in yields of less than 10 % .

To carry out the oxidation according to the invention, the 3-methyl-2-butene-1-al-acetals of the formula II are heated with selenium dioxide in the above solvents for a certain reaction time to reaction temperature.

Selenium dioxide is advantageously used in approximately molar amounts. But you can also work with an excess or deficit of up to 15 % of theory without significantly influencing the yields.

The reaction time is generally 2 to 20, preferably 5 to 15 minutes.

The reaction temperature is generally from 70 to 170 ^° C., preferably from 80 to 120 ^° C.

The reaction mixture is worked up in the usual way, for example by adding about 3 times the amount of water to the cooled reaction mixture and extracting several times with an inert solvent which is immiscible or only slightly miscible with water, washing, drying and distilling the combined organic phases under reduced pressure. Since the desired trans-3- methyl-2-butene-l, 4-dial-l-acetals of the formula I the only volatile substances are _s arising in these oxidation reactions, their isolation possible in a very simple manner by distillation from the undistillable polymeric selenium-containing material in a thin-film evaporator.

According to NMR spectroscopic and gas chromatographic analysis, practically only the trans compounds are obtained in this production process, which is very important for use in carotenoid syntheses. The Makin et al (Ie) produced 3-methyl-2-butene-l, ⁱ i-dial-l-diethylacetal is against stereochemically undefined.

KfIQR? 9/1 Π 1 fi "5-

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The trans-3-methyl-2-butene-l, 4- -dial-1-acetals I have not yet been described in the literature been. They are of extraordinary interest as building blocks in the synthesis of carotenoids, since one can use them produce countless substances of great biological and pharmacological importance in a simple manner by successive Wittig syntheses can. The possibility of a gradual build-up of carotenoids lies in the fact that these compounds I have 2 functional groups in the right place for carotenoid syntheses, in which one Wittig reaction can start, of which, however, always one is blocked and this only occurs after the 1st Wittig reaction has taken place can be activated easily by hydrolysis. For example, one of the tech .- "· ' niche vitamin Α syntheses, the ß-Jonylidenäthyl-triphenylphosphoniumchlorid and the compounds prepared according to the invention by Wittig synthesis and subsequent acidic hydrolysis directly with extraordinarily good yields Making retinal. Retinal itself is of great economic, biological and pharmacological importance .. In its vitamin action the retinal corresponds to the effect of retinol (vitamin A) (cf. J. Amer. Chem. Soc. 7j? (1950), page 239).

The production of retinal was previously only possible in a cumbersome way, for example by oxidizing vitamin A with manganese dioxide or nickel peroxide. This oxidation only takes place with yields of 60-70 %. and causes considerable disposal problems.

Furthermore, retinal is of great importance as a building block for a ' extremely economical synthesis of ß-carotene: namely, retinal can be used in a simple manner and in extremely good yields with the retinylphosphonium chloride, which can be prepared from retinol (vitamin A), can be converted into ß-carotene. This procedure has been around since 1959 known (cf. DT-PS 1 068 709), but so far no technical Become important because there is still no economical process for the production of the retinais required for this was.

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example 1

A solution of 2.84 g (20 mmol) of 3-methyl-2-buten-l-al- (l », 3'- propylene) acetal in 20 ml of dioxane is mixed with 2.2 g (20 mmol) of selenium dioxide and refluxed for 10 minutes. the The mixture takes on a gray-brown color.

After cooling, 60 ml of water are added and the mixture is extracted three times with 40 ml of benzene each time. The benzene extracts are combined, washed with aqueous NaHCO 3 solution and then with water and dried over sodium sulfate. The solvent is then distilled off on a rotary evaporator. The brown residue (3.8 g) yields upon distillation under greatly reduced pressure in a Kugelrohr (bath temperature 7O ⁰ C at 0.1 mm Hg) 1.84 g of 3-methyl-2-butene -l, 4-dial-l - (l ^r , 3'-propylene) acetal, which, according to gas chromatographic analysis with an internal standard, had a content of 93 % . This corresponds to a total yield of 55 % of theory, based on the 3-methyl-2-buten-1-al- (I ¹ , 3'-propylene) acetal used.

Example 2

A mixture of 3.4 g (20 mmol) of 3-methyl-2-buten-1-al- (2 ', 2'- dimethyl-1 ¹ , 3'-propylene) acetal and 2.2 g (20 mmol) selenium dioxide in 25 ml of dioxane is refluxed for 10 minutes. After cooling, 60 ml of water are added to the dark brown solution and the mixture is extracted three times with 40 ml of benzene each time. The work-up of the benzene phase is carried out as described in Example 1. Is obtained as a crude product 4.1 g of a dark brown oil which upon distillation under greatly reduced pressure in a Kugelrohr (bath temperature 8O ⁰ C at 0.1 mm Hg) 2.27 g of 3-methyl-2-butene, l, 4- dial-1- (2 ^f , 2 »-dimethyl-1 ', 3'-propylene) acetal provides. According to analysis by gas chromatography, the fraction showed a content of 94 %, which corresponds to a yield of 58 % of theory.

Example 3

3.4 g (20 mmol) of 3-methyl-2-buten-1-al- (2 », 2'-dimethyl-1 ', 3'-propylene) acetal and 2.2 g (20 mmol) of selenium dioxide become ^{heated to 110 °} C. for 15 minutes with stirring in 30 ml of chlorobenzene.

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Λ *

After cooling, the brown solution is washed twice each with aqueous sodium hydrogen carbonate solution and water and then dried with magnesium sulfate. After the solvent has been stripped off, 4.3 g of a brown oil remain, which on distillation under greatly reduced pressure in a bulb tube (approx. 80 ° C. at 0.1 mm Hg) gives 1.97 g of a pale yellow fraction. The 3-methyl-2-butene-1,4-dial-1- (2 ', 2 ^! - -dimethyl-1 ¹ , 3'-propylene) acetal content of this sample was determined by gas chromatography to be 88 % , which corresponds to a yield of 47 % of theory.

Example 4

A suspension of 60 g (0.55 mol) of selenium dioxide in 500 ml of dioxane was heated to 80.degree. 85 g (0.5 mol) of 3-methyl-2- -butene-l-al- (2 ', 2'-dimethyl-l', 3'-propylene) -acetal flow and keeps the mixture boiling under reflux for 10 minutes. The reaction mixture is then cooled in an ice bath.

Working up: After adding 1 liter of water, the mixture is extracted three times with 300 ml of benzene each time, the extracts are combined and purified by filtering them through a 10 cm thick layer of silica gel. The benzene solution is concentrated under reduced pressure and the brown oil which remains is subjected to distillation under greatly reduced pressure in a thin-film evaporator. The distillate can be further purified by fractional distillation; 59 g of a colorless liquid with a boiling point of Kp _Q ^ = up to 69 ° C, the content of 3-methyl ~ 2-butene-1,4-dial-i- (2 ', 2'- -dimethyl-1 ¹ , 3'-propylene) acetal was determined to be 97% by gas chromatography. This corresponds to a total yield of 62 % of theory.

The selenium content of this fraction is 0.1 %. The NMR spectrum is evidence of the structure of the product:

^H ALD 9 , 27 ppm J 5.5 Hz with the ^H ACET 5 , 04 ppm Remote coupling ^H VINYL 6th , 20 ppm

Protons of the CH, ~ group

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The 3-methyl-2-butene-l, 4-dial-l- (2 ', 2'-dimethy1-1', 3 ^? -Propylene) acetal prepared according to Example 4 shows a cis-trans ratio of 8: 92; the indicated NMR data relate to the trans form.

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Claims (4)

- ψ - "O. Z. 30 220 patent claims 1. Process for the preparation of t "rans-3-methyl-2-butene-l, ^ -dial-1-acetals of the general formula I. R ^J R ^u H · ■ 1 ß
in which R to R are hydrogen or an alkyl group with 1 to 4 carbon atoms, preferably a methyl group, characterized in that a 3-methyl-2-buten-1-al-acetal of the general formula II R ² R ¹ " ^ C. CH - CH = C - CH ₃ (II), C - 0 Eat
in which R to R have the abovementioned meaning, in an ether with a boiling point of 70-170 ⁰ C, benzene, an inert or halogenated monocyclic aromatic hydrocarbon oder.einem multi-alkyl-substituted ¹ fachchlorierten aliphatic hydrocarbon having a boiling point between 70 and 170 ⁰ C as a solvent oxidized with selenium dioxide. 2. The method according to claim 1, characterized in that the oxidized 3-methyl-2-buten-l-al-acetal of the formula II at temperatures of 80 ⁰ C to 120 ⁰ C with selenium dioxide. - 10 - - 10 - 0.1. ^ O 220 3. The method according to claim 1, characterized in that a reaction time of 5 minutes to 15 minutes is observed in the oxidation of the 3-methyl-2-buten-1-al-acetal of the formula II. 4. The method according to claim 1, characterized ₃ that one for the oxidation of 3-methyl-2-butene-l-al-acetal of
Formula II uses approximately molar amounts of selenium dioxide. BASF Aktiengesellschaft 1niQ