DE2309885C3 - 2 (3) -Methyl-1-acetoxy-4-alkoxy (phenoxy) -1,3-butadienes and process for their preparation - Google Patents

Description

R- R ¹

U)

The invention relates to 2 (3) -methyl-1-acetoxy-4-alkoxy (phenoxy) -1,3-butadienes and their preparation from 2 (3 (-Methyl-4-alkoxy- (phenoxy) -crotonaldehyde or from 2 (3) -Methyl-1-acetoxy-4,4-dialkoxy-2-butene.

The new compounds are of exceptional interest as intermediates in the synthesis of carotenoids. For example, by reacting 2-methyl-l-acetoxy-4-methoxy-l, 3-butadiene with chlorine or bromine at temperatures below C and then adding an alcoholic solution of an alkali metal alcoholate and a / i-Jonylidenäthyltriphenylphosphoniumsalz to the reaction mixture in a simple manner a one-pot process, the retinal, which was previously only elaborately prepared, in which R ¹ and R ^{2 are} different and represent hydrogen or methyl and R ^{3 represents} an aliphatic hydrocarbon radical with 1 to 4 carbon atoms or a phenyl radical, can, for example, be produced very advantageously by adding a methyl-4-alkoxy (pihenoxy) crotonaldehyde of the formula II

55 R 'C) CH, CCC
R-- R ¹

Il

in which R ¹ to R ^{3 have} the meaning given above, heated with excess acetic anhydride and an alkali acetate, carbonate or hydroxide or a non-aromatic acyclic amine.

4-Alkoxymethyl-croton-aldehydes of the form required as starting materials for this process

mel II can be easily produced in the following way, for example:

() - ■ - ■ CH -C --- CU CH, Cl

ΠΙ,

H C (O / \ lk \ l),

Alkvl O

Alk \ I O

CH C CH-CH ₁ Cl

CH,
Well,

CH ₃ OH

Alk \ l O

CH - C - CH - CH ₁ - OC-H,
Alks IO CU,

H, O

O CH —C- CH CU ₂ OCH,
CU,

Examples of suitable starting materials are: 2-methyl-4-methoxy-but-2-en-1-al, 2-methyl-4-ethoxy-but-2-en-1-al, 7- methyl-4-isopropoxy -but-2-en-1-al, 2-methyl-4-phenoxy-but-2-en-1-al, 3-methyl-4-methoxy-but-2-en-1-al and 3-methyl-4 ethoxy-but-2-en-1-al.

The acetic anhydride for the production with these aldehydes is used in quantities from 1 to 7 moles, preferably 2 to 3 moles per mole of starting compound.

Sodium and potassium acetate are preferred as effective alkali acetates, carbonates or hydroxides as well as potassium carbonate and potassium hydroxide. The alkali acetates, carbonates and Hydroxides are generally used in amounts of 0.3 to 3 mol, depending on the type of alkali compound per mole of starting compound. For example, when using potassium carbonate, 0.5 moles per Mol of starting compound is sufficient, while when using potassium acetate with advantage 2 to 3 moles are used per mole of starting compound.

When using sodium acetate, the reaction time for this reaction step is about 5 to 9 hours while using potassium acetate, potassium carbonate and hydroxide for the same Degree of conversion is only about 1 to 2 hours, preferably 40 to 80 minutes.

As non-aromatic bicyclic amines, for example, 1,4-diazobicyclo- [2,2,2] -octane (DABCO) or 1,5-diaza-bicyclo- [4,3,0] -nonen- (5) into consideration.

The usual amines such as ethylamine, triethylamine, pyridine and quinoline, on the other hand, can lead to this reaction Not used. The non-aromatic acyclic amines are generally used in Amounts of preferably 0.5 to 2 moles per mole of starting compound.

The reaction mixture is worked up in the customary manner, for example by stirring with a water-immiscible solvent, preferably diethyl ether or benzene, removing the alkali acetate by removing the ears or by washing the mixture with water and then washing it fractional distillation of the organic phase or simply by adding water, separation and fractionating the upper phase. The 2 (3) -Methyll-acetoxy-4-alkoxy (phenoxy) -l, 3-buladienes are obtained as a mixture of essentially two geometric isomers.

Examples 1 to 7 illustrate this process.

It has also been found that the methyll-acetoxy-4-alkoxy -], 3-butadienes of the formula I is also obtained very advantageously if methyl-1-acetoxy-4,4-dialkoxy-2-butenes are used of formula 111

CH CC CH ₁ -O- CO ClI,

R- R ¹

around

in which R ¹ and R ^{2 have} the meaning given above

»5 and R ^{3 is} an aliphatic hydrocarbon radical with 1 to 4 carbon atoms, heated ^{to temperatures of 150 to 260 °} C., preferably 175 to 210 ° ^C. , in the presence of p-toluenesulfonic acid and quinoline. It was surprising that, under the reaction conditions mentioned, the compounds of the formula I are obtained in good yields, since they are enol esters or enol ethers which are generally obtained at such high temperatures in the presence of acids and / or basic catalysts and alcohols (R ₃ OH) can be rapidly decomposed by transesterification.

The 2 (3) -methyl-1-acetoxy-4,4-dialkoxy-2-butenes required as starting material for this process can be prepared in a simple manner by acetalizing the corresponding methyl-acetoxy-2-butenals. The 3 (2) -Methyl-4-acetoxy-2-buten-1-ale is obtained, for example, by reacting ω-chloro- or ω-bromo-tiglic aldehyde with alkali or alkaline earth acetate (cf. DT-PS 12 27 000 ) or by rearrangement of 2-FormyI-2-hydroxybut-3-en or its acetate in the presence of copper compounds (cf. DT-PS 12 97 597). The acetalization of the 3 (2) -methyl-4-acetoxy-2-buten-1-ale is carried out in a known manner by reacting the butenals with alcohols in the presence of an equimolar amount of the corresponding orthoester with the aid of acidic catalysts.
The process according to the invention is expediently carried out by adding p-toluenesulphonic acid and quinoline to the reaction mixture obtained in the acetalization of the 3 (2) -methyl-4-acetoxy-2-buten-1-ale with a lower alcohol and adding to it the reaction temperature is heated.

If the reaction mixture formed during the acetalization is used as the starting material for When the process according to the invention is used, it is advantageous to also carry out the acetalization with p-toluenesulfonic acid to catalyze.

p-Toluenesulfonic acid is used according to the invention. ^ - moderately in amounts of 0.5 to 4 mol percent, quinoline in amounts of about 2 to 20 mol percent, based on the starting compound III.

The reaction temperature is 150 to 260 ° C, preferably 175 to 21O ⁰ C.

The reaction can be carried out under normal pressure or reduced pressure. If you work at a diminished level Pressure, it must be ensured that the starting compounds [2 (3) - methyl-4-acetoxy-2-butenal-dialkyl acetals] are not yet volatile at the required reaction temperature.

The reaction time is generally 10 to 30 minutes.

Examples 8 to 10 are intended to illustrate this process.

In principle, one can implement the methylacetoxy-4,4-diaIkoxy-2-butenes to the 1,3-butadiene (I) according to the invention also in the presence of others weakly acidic catalysts, for example Siükagel, Aluminum oxide powder (acidic), sodium dihydrogen phosphate, ammonium dihydrogen phosphate or potassium bisulfate carry out, but achieved in the reaction with p-toluene sulfonic acid and quinoline the best results.

With the help of the inventive method it was For the first time possible, the extremely interesting new intermediates for the synthesis of carotenoids 2 (3) -Methyl-1-acetoxy-4-alkoxy (phenoxy) -1,3-butadienes of the formula I. The processes can be implemented and run in a relatively simple manner generally with quite good yields. Furthermore, the new 2 (3) -Methyl-1-acetoxy-4-alkoxy- (phenoxy) -l, 3-butadienes I are used with particular advantage for the preparation of methylfumaric dialdehyde monoacetals of formula IV

R- ¹ OH

CH-C-C-C

R ⁴ O R- R ¹ O

(IV)

in which R ¹ and R ^{2 have} the meaning given above and R ³ and R ^{4 are} identical or different and each represent an aliphatic hydrocarbon ^{radical having 1 to 4 carbon atoms and R 3} also represents a phenyl radical. The methylfumaric dialdehyde monoacetals (IV) are also compounds which are of exceptional interest as intermediates in the synthesis of carotenoids.

example 1

a) A mixture of 114 g (1 mol) of 2-methyl-4-methoxy-but-2-en-1-aI (4-methoxy-tiglic aldehyde, 500 g of acetic anhydride and 196 g (2 mol) of anhydrous potassium acetate is added with stirring and reflux cooling in a 2-1 flask for 50 minutes at about 135 ° C. After the reaction mixture has cooled to room temperature, it is stirred with 700 ml of diethyl ether and the precipitated potassium acetate is suctioned off. The filtrate is fractionated on a 20 cm long Vigreux column . the fraction of boiling point Kp. _o5 = 50 to 65 ⁰ C consists of a mixture of cis-trans-isomers of 1-acetoxy-2-methyl-4-methoxy-buta-l, 3-diene. the yield is 70% the theory.

NMR (σ [ppm], CDCI ₃ , TMS)

AcO- CH ₁ --C ₁ -CH,

C ₁ -H 7.07 (S, 1H)
C ₄ -H 6.55 (d, IH, Ja ·) 13 Hz)
C ₁ -H 5.48 (d, 1H, Jab13Hz)
CH ₃ O- 3.58 (S, 3 H)

(H,
AcO CII C CII CII OCII,

C ₁ -H 6.81 (S, 1H)
C ₃ -H 5.92 (d, IH, Jab13Hz)
C ₄ -H 6.60 (d, IH, J from 13 Hz)
CH ₃ O- 3.63 (S, 3H)

b) If you work as described in Example 1 a), but used instead of 196 g of potassium acetate 164 g (2 mol) of anhydrous sodium acetate and heat the reaction mixture instead of 50 minutes 8 hours at about 135 ° C., 107 g of emes are obtained cis-trans isomer mixture of l-acetoxy-2-methyl-4-methoxy-buta-1,3-diene.

The yield is 68% of theory.

Example 2

If you work as described in Example 1 a), but instead of 114 g of 2-MethyI-4-methoxybut-2-en-1-al 128 g (1 mol) of 2-methyl-4-ethoxy-but-2- en-l-al (4-ethoxy-tiglic aldehyde), we obtain 126g of a distillate of boiling point Kp. _O6 = 53-69 ° C, according to gas chromatographic and NMR spectroscopic examination of two cis-trans isomers of l-acetoxy-2 -methyl-4-ethoxy-buta-1,3-diene.

The yield is 74% of theory.

Example 3

A mixture of 114 g of 2-methyl-4-methoxy-but-2-en-l-al, 500 g of acetic anhydride and 112 g (1 mol) of l ^ -diaza-bicyclo-P ^^ J-octane (DABCO) is heated with stirring and reflux in a 2-1 flask at about 135 ° C for 1 hour. After the reaction mixture has cooled to room temperature, it is mixed with 600 ml of benzene and washed 3 times with 500 ml of water each time. In the fractionation of the organic phase gives 101 g of a fraction having the boiling point Kp. _{0, 5} = 50 to 65 ⁰ C, which by gas chromatography and NMR spectroscopic examination of ehiem mixture of three cis-trans-isomers of l-acetoxy ^ -methyM-methoxybuta-1,3-diene consists.
The yield is 62%.

35

55

Example 4

A mixture of 71 g (0.5 mol) of 2-methyl-4-isopropoxy-but-2-en-1-aI, 250 g of acetic anhydride and 98 g (1 mol) of anhydrous potassium acetate is stirred and refluxed for 45 minutes for about 135 ° C heated. After cooling the reaction mixture, stirring with 350 ml of diethyl ether, suction of potassium acetate and fractionation of the filtrate is 136 g of a fraction having a boiling point Kp. _Oil = 55 obtained to 56 ° C, consisting of l-acetoxy-2-methyl-4-isopropoxy -buta-l, 3-diene consists.

The yield was 74% / / W Th, »™;»

25 09 885

Example 5 Example 8

A mixture of 176 g (1 mol) 2-methyl-4-phenoxybut-2-en-l al, 50Og acetic anhydride and 196 g (2 mol) anhydrous potassium acetate is stirred and cooled in a 2-1 flask to about 135 ⁰ C heated. After the reaction mixture has cooled, it is mixed with 600 ml of benzene, the precipitated potassium acetate is filtered off and the filtrate is fractionated. 186 g of a fraction with a boiling point of bp. _{0> 3} = 108 to 112 ° C., which consists of l-acetoxy-2-methyl-4-phenoxy-buta-1,3-diene, are obtained.

The yield is 85% of theory.

Example 6 _{$ 1}

A mixture of 114 g (1 mol) of 2-methyl-4-methoxybut-2-en-1-al, 200 g (2 mol) of acetic anhydride and 69 g (0.5 mol) of anhydrous potassium carbonate is stirred for about 1 hour heated to reflux temperature (about 135 ° C) for a long time. It is then cooled to room temperature, water is added until the salts are dissolved, the upper phase is separated off, the aqueous phase is extracted with a little benzene and the combined organic phases are fractionated. This gives 132 g of a fraction having a boiling point Kp. _{0, 8} = 48 to 55 ⁰ C, as the -methyM-butadiene-methoxy-1,3 consists of cis-trans-l-acetoxy ^.

The yield is 85% of theory.

Example 7

A mixture of 114 g (1 mole) of 3-methyl-4-methoxybut-2-en-l-al, 500 g acetic anhydride and 207 g (1.5 mol) of anhydrous potassium carbonate is heated with stirring under reflux to about 135 ⁰ C. The cooled reaction mixture is stirred with 700 ml of ether, the precipitated potassium salt is filtered off with suction, the filtrate is concentrated in a rotary evaporator and the residue is fractionated. This gives 106 g of a fraction having a boiling point Kp. _{0> 4} = 48 to 55 ⁰ C, which, 3-dien from a mixture of cis-trans-isomers of 1-acetoxy-3-methyl-4-methoxy-buta-l consists.

The yield is 65% of theory.

28.4 g (0.2 mol) of 2-methyl-4-acetoxy-2-butenal are added to a mixture of 23.3 g (0.22 mol) of methyl o-formate, 12.8 g (0.4 mol) Methanol and 0.35 g (2 mmol) of p-toluenesulfonic acid were added dropwise. Acetalization occurs when the temperature rises. After one hour, add 2 g (ISmMoI) quinoline and heated at 200 Torr for 20 minutes at 185 to 19O ⁰ C (internal temperature). The split off methanol is distilled off over a 20 cm column. The pressure is then adjusted to 20 Torr, with 23.2 g of 1-acetoxy-S-methyM-methoxy-1,3-butadiene passing over as a mixture of two geometric isomers.

The yield is 75% of theory.

Example 9

28.4 g (0.2 mol) of 2-methyl-4-acetoxy-2-butenal are converted into 1-acetoxy-2-methyl-4-methoxy-1,3 via the dimethylacetal as an intermediate in a manner analogous to that described in Example 8 - butadiene, bp _0, converted 5 = 50 to 65 ⁰ C.. The yield is also 75% of theory.

Example 10

From 28.4 g (0.2 mol) of 2-methyl-4-acetoxy-2-butanal, 32.0 g (0.22 mol) of o-ethyl formate and 23 g (0.5 mol) of ethanol is obtained through Adding a catalytic amount (about 2 mmol) of p-toluenesulfonic acid produced the diethyl acetal. After one hour, 2 g (15 mmol) of quinoline are added and the mixture is heated under 240 torr for 25 minutes at 190 to 195 ° C. Excess o-formic acid ester and ethanol are distilled off over a 20 cm column. Thereafter, the pressure to about 20 Torr is reduced, whereby 22.1 g of l-acetoxy-3-methyl-4-ethoxy-l, 3-butadiene as a mixture of two geometric isomers of Kp.jjo = 102 to 11O ⁰ C pass.

The yield is 65% of theory.

609 650/267

Claims (3)

Patent claims: I. Metini- 1 -acciuw -4-; '. Lko \\ (pheno \\ i- 1.3-hulailienc of the general formula I. R -'- O-CH CC CH-O-CO ClI, R- R ¹ St. in which R ¹ and R ^{2 are} different and represent hydrogen or methyl and R ^{3 represents} an aliphatic hydrocarbon radical having 1 to 4 carbon atoms or a phenyl radical. 2. Process for the preparation of compounds according to claim], characterized in that one is a methyl-4-alkoxy (phenoxy) crotonaldehyde of the formula II 20 H. - ¹ O CW ₂ CCC R ^: W C) in which R ¹ to R ^{; l have} the meaning given above, heated with excess acetic anhydride and an alkali acetate, carbonate or hydroxide or a non-aromatic acyclic amine. 3. Process for the preparation of compounds according to claim 1, characterized in that methyl-1-acetoxy-4,4-dialkoxy-2-butenes of the formula III R 'C) CH CC CW ₂ --C) CO CW, R 'C) R ² IV (III) produce. Retinal has practically the same effect as vitamin A and differs from it characterized by greater stability against acids and oxidation. Retinal is also of great importance as a Direct preliminary product in an extremely economical synthesis of /? - Carot: n, which is used as a food coloring and provitamin-Α is of great interest. Retinal can be done in a simple way and with extremely good yields with the retinylphosphonium chloride which can be prepared from retinol (vitamin A) / 3-carotene are implemented. This procedure has been around since Known in 1959 (cf. DT-PS 10 68 709), but has not yet been able to acquire any technical significance because it is still no economical process for the production of the retinais required for this was available. The production of retinal was previously only possible in a complicated manner, for example by reacting a / J-Jonyliden-äthyltriphenylphosphoniumsalzes with the difficult to access /? - FormyI-crotyl acetate under the conditions of the Wittig synthesis, hydrolysis of the vitamin A acetate formed and then Oxidation of vitamin A with manganese dioxide or nickel peroxide. This oxidation only proceeds with yields of 60 to 70%. In addition, this vitamin A oxidation is technically difficult to carry out and is associated with great environmental problems, since 10 to 20 times the amount by weight of MnO ₂ must be used for this conversion. With the aid of the 2-methyl-1-acetoxy-4-alkoxy according to the invention (phenoxy) -l, 3-butadiene, on the other hand, it is possible to use retinal and thereby also / J-carotene to manufacture in a simple and economical way. By reacting 3-methyl-l-acetoxy-4-methoxy-l, 3-butadiene with chlorine or bromine at temperatures below 10 ⁰ C and then adding an alcoholic solution of an alkali metal and a Retinyltriphenylphosphoniumsalz are obtained in an elegant manner the / J Apo-Cas-Carotinal, which is of great interest as a food coloring and provitamin-Α. The new methyl-1-acetoxy-4-alkoxy (phenoxy) -1,3-butadienes of Formula 1 in which R ¹ to R ¹ as defined above, have, heated in the presence of p-toluene sulfonic acid and quinoline at temperatures of 150 to 260 ° C, preferably 175-210 ⁰ C. 45 R- 'O ClI C' C CW C) CO CH,