The way to obtain 2,6-dimethyl-10-methylene-4 - c1- c4- alkoxycarbonyl-2,6,11-dodecatrien

 

The invention relates to organic chemistry, in particular, to a method for producing 2,6-dimethyl-10-methylene-4-C1-C4arcoxia - bonil-2,6,11-dodecatrien.

The aim of the invention is to develop a method of producing 2,6-dimethyl-10-methylene-4-C1-C4-alkoxycarbonyl-2,6,11-dodecatrien - on, allowing for its use as intermediate compounds in the synthesis of vitamin E to receive the latter with a higher yield.

The invention is illustrated by the following examples.

The original 3-hlormaren get out of myrcene with access to 84.6% by well-known methods.

P R I m e R 1. Into a flask of 100 ml is injected in the atmosphere of argon, 10 ml of dry pentane, 2,07 Diisopropylamine (20 mmol). After cooling to 0aboutWith add 12.5 ml of a solution of n-utility in hexane (1.6 M/l), which corresponds to 20 mmol. The reaction mixture is left for 20 min at 0aboutWith, after which it is cooled to -78aboutC. To the reaction mixture slowly add 2,78 g of ethyl ester of 4-methyl-3-pentenol acid (20 mmol), after which it is left for 20 min at -78aboutC and then for 1 hour at a temperature of about 20aboutC.

In the second flask 100 ml injected into the atmosphere Argo is 5 g of 6-chloro-3-methylene-7-methyl-1,7-octadiene (20 mmol).

With a needle for transfer of reagents into the second flask enter the carbanion obtained in the first flask, this operation takes 20 min, after which the reaction mixture is left for 2 hours at a temperature of about 20aboutC. the Color of the solution changed from light yellow to orange. The reaction mixture was poured into 30 ml of 10% hydrochloric acid. The aqueous phase is separated by decantation and extracted with ether. The organic phase is collected and dried over magnesium sulfate. After filtration and removal of the solvent receive 5,08 g butter yellow color. As the result of acceleration under reduced pressure (temperature 111-118aboutWith 1.4 mm RT.article; 0,18 kPa) to obtain 4.5 g of a mixture of products 1 and 2: 1) (CH3)2C= CH-CH(CO2C2H5)-CH2-C(CH3)= CH-CH2-C(= CH2)-CH= CH22) CH2= C(CH3)-CH-/CH(CO2C2H5)-CH= = C(CH3)2/-CH2-CH2-C(= CH2)-CH= CH2The output is of 81.5%. Analysis by chromatography in gas phase gives the ratio of the quantities = 98%.

The structure of the resulting product is confirmed by IR spectra, mass spectra and spectra, proton nuclear magnetic resonance (PMR).

Connection 1: mass spectrum: m/e = 276 (M+)

IR-spectrum (Planck CDCl3offset in parts per million)

m - a comprehensive array; S = singlet; d = doublet; t = triplet; q = keyrepeat; I = coupling constant in Hz.

Connection 2: mass spectrum: m/e = 276 (M+)

range PMR (360 MHz, CDCl3offset in parts per million)

< / BR>
P R I m m e R 2 illustrates the use of product 1 for the synthesis of vitamin E.

a) In a three-neck flask of 100 ml equipped with a reflux condenser and a thermometer, is injected at a temperature of about 20aboutFrom 22.9 g of product combinations, obtained according to example 1, which corresponds to 87,4 the mmol, 0,0458 g /Ph Cl (1, 5cyclooctadiene)/(0,186 grammatim Ph), 0,0847 g Na2CO3(0.8 mmole), 1,110 land only g traintravel salt three(metasulfite)phosphine (TPPTSNa), 20 ml of ethanol-water (75-25 by volume) and 22,36 g methylacetoacetate (192 mmole). The reaction mixture is left at the 75aboutC for 24 hours, After cooling the solution to it was added 100 ml of ether. After desantirovaniya the organic phase is washed with three portions of 30 ml of water. The solvent is distilled off and remove the remaining mass of 100 ml of pentane. Then the organic phase is washed with three portions of 30 ml of water, combine the organic phase and dried over magnesium sulfate. After filtration and distillation of RA is(CO2CH3)-CH2-C(CH3)= = CH-CH2CH2-C(CH3)= CH-CH2-CH(CO2CH3)- -CO-CH3and (CH3)2C=CH-CH(CO2CH3)-CH2-C(CH3)= =CH-CH2-CH2-C(= CH2)-CH2-CH2- CH(CO2CH3)-CO-CH3The output is 93.7%.

Mass spectrum: m/e = 378 (M+)

IR spectrum (film), cm-1: 1740 [C=0 (ester)], 1720 [CO (ketone)], 1645 (C=C), 1160 (C-O), and 895 (C=CH2; = CH)

range PMR (360 MHz, CDCl3the shift in parts per million).

b) In the flask 100 ml injected 29,95 g of the product obtained according to example 2A (79,2 mmole), 31 g of the solution 30,75% of the hydroxide of sodium, which corresponds 0,238 mole of hydrate of sodium oxide and 60 ml of water. The reaction mixture is left for 1 hour at a temperature of 40aboutWith until a homogeneous yellow solution, after which there was added 7 ml of 95% sulfuric acid and 18 ml of water. The reaction mixture is again left for 1 hour at a temperature of 25aboutC. While there is plenty of carbon dioxide. The resulting solution was extracted with three portions of 30 ml of ether, the combined organic fractions and dried over magnesium sulfate. After filtration and distillation of the solvent to be obtained with a yield of 95% 23,19 g of a mixture of products is2- -CO-CH3(CH3)2C=CH-CH(CO2H)-CH2-C(CH3)= =CH-CH2CH2-C(=CH2)-CH2-CH2-CH2-CO-CH3< / BR>
Mass spectrum: m/e = 306 (M1)

IR spectrum (film), cm-1: 1710 (C=O), 1600 (C=C), 895 (C=CH2) and 840 cm-1(C=CH)

range PMR (360 MHz, CDCl3offset in parts per million).

< / BR>
C) In an autoclave at 125 ml stainless steel is introduced into the argon atmosphere 5 g of the product obtained according to example 2B (16.3 mmole), 30 ml of pentane and 0.2 g of 10% palladium on charcoal, and then introducing hydrogen to a pressure 100 bar. The reaction mixture is left for 12 hours at a temperature of about 20aboutC. After filtration and removal of the solvent receive a colorless oil, containing 98% of the product of the formula: (CH3)2CH-CH2-CH(CO2H)-CH2-CH(CH3)- -CH2-CH2-CH2-CH(CH3)-CH2-CH2-CH2-

-CO-CH3< / BR>
The structure of the obtained product is confirmed by mass spectra, IR spectra and spectra proton NMR and carbon (C13nuclear magnetic resonance.

In the heat treatment of the obtained product at 150aboutTo get phyto is2-CH2-CH2-CO-CH3. Output 90%.

The hydrogenation product before heat treatment:

mass spectrum: m/e = 312 (M+)

IR spectrum (film), cm-1: 1710 (C=O).

The IR spectrum of Fiona identical IR spectrum described in the literature.

d) Translation of Fiona in vitamin E-known method.

Thus the proposed method allows to obtain 2,6-dimethyl-10-methylene-4-C1-C4-alkoxy-carbonyl-2,6,11-Daudet - sodium, the use of which as an intermediate product in the synthesis of vitamin E enables you to obtain the latest with a higher yield (54.1 per cent).

THE WAY TO OBTAIN 2,6-DIMETHYL-10-METHYLENE-4 - C1-C4-ALKOXYCARBONYL-2,6,11-DODECATRIEN, characterized in that C1-C4-alkilany ether 4-methyl-3-pentenol acid is subjected to unionization butyllithium in the presence of Diisopropylamine obtaining anion of the formula

CH3-H-CHCOOR ,

where R is C1- C4-alkyl,

which is subjected to interaction with 7-methyl-3-methylene-6-chloro-1,7-octadiene at 20 - 25oIn the presence of palladium catalyst, modified with triphenylphosphine in an environment aprotic solvent.

 

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