PL210088B1 - Method of manufacturing of (E)-4-t-butylcyclohexanol - Google Patents

Description

The subject of the invention is a process for the preparation of (E) -4-t-butylcyclohexanol. This compound in its pure form can be used in chemical synthesis, e.g. for the preparation of diastereomerically pure esters of 4-t-butylcyclohexanol.

(E) -4-t-Butylcyclohexanol can be obtained by reducing Meervein-Ponndort-Verley of 4-t-butylcyclohexanone with propan-2-ol in the presence of Al (Oi-C3H7) 3. A mixture of diastereomeric alcohols with a composition of 79% of the (E) isomer and 21% of the (Z) isomer is obtained. The mixture is separated by fractional crystallization of the hydrogen phthalates of these alcohols.

In the case of reduction of 4-t-butylcyclohexanone with sodium borohydride in a hydroalcoholic solution, a quantitative yield of a mixture of diastereoisomeric alcohols composed of 80% of the (E) isomer and 20% of the (Z) isomer is obtained. The resulting mixture is separated into diastereoisomers.

A known method of obtaining (E) -4-t-butylcyclohexanol is also the reduction of 4-t-butylcyclohexanone with lithium aluminum hydride in diethyl ether or tetrahydrofuran.At quantitative conversion of the substrate, a mixture of alcohols containing 92% of the (E) isomer and 8%) of the (Z) isomer is obtained. ).

Higher diastereoselectivity of reduction is obtained when using as the reducing agent AlH3-xCl, formed as a result of the reaction between ether solutions of LiAlH4 and AlCl3.As a result of the reduction of 4-t-butylcyclohexanone with this reducing agent, a mixture containing 3.2% of unreacted substrate, 96.0% of alcohol ( E) and 0.8% alcohol (Z). Pure (E) alcohol is obtained by fractional crystallization from petroleum ether.

Another method of obtaining (E) -4-t-butyl-cyclohexanol is the reduction of 4-t-butylphenol with hydrogen in the presence of Adams's catalyst (PtO2) in acetic acid solution. The resulting mixture of diastereoisomeric alcohols was separated by column chromatography.

The main disadvantage of the discussed methods is the formation of a mixture of diastereoisomeric alcohols in each case and the need for quite costly and laborious separation of this mixture into pure diastereoisomers. Most of the methods described above are non-catalytic methods, which use significant amounts of inorganic reactive reducing agents, the transformation products of which, after synthesis, constitute troublesome waste. Moreover, the use of these reducing agents entails the use of anhydrous conditions during the synthesis, as well as the use of anhydrous, volatile, highly flammable ethers which easily form very dangerous peroxides on contact with air oxygen.

On the other hand, in the catalytic method of reducing 4-t-butylphenol with hydrogen, a very expensive platinum catalyst and acetic acid are used as a solvent.

The method according to the invention avoids the above-mentioned difficulties.

The method of producing (E) -4-t-butylcyclohexanol is based on the reaction of 4-t-butylcyclohexanone and a secondary alcohol in a molar ratio of 1: 2 to 1:12, at the boiling point of the mixture and in the presence of magnesium oxide as a catalyst, previously calcined at a temperature of 573-1073 K, in a stream of air or inert gas for 1 to 10 hours. The mixture is then filtered to isolate the catalyst and the filtrate is distilled to isolate the product.

Preferably, propan-2-ol or butan-2-ol is used as the secondary alcohol. Preferably, magnesium oxide with a grain size of 0.05-2.5 mm is used.

The method according to the invention consists in a liquid phase hydrogen transfer reaction from alcohols to 4-t-butylcyclohexanone in the presence of a catalyst. Due to the high diastereoselectivity of the conversion (> 98%), there is no need for costly and laborious separation of the alcohol diastereoisomers. The catalyst is cheap and non-toxic. Secondary alcohols are readily available, cheap and have a very low toxicity. Moreover, the separation of the mixture after the reaction is not difficult, as it contains compounds with significantly different boiling points.

The method according to the invention is presented in more detail in the application examples.

P r z k ł a d I

A solution of 3.86 g (0.025 mol) of t-BuON in 12 g (0.2 mol) of 2-propanol is poured into a dry glass set consisting of a reactor with a flat bottom, equipped with a magnetic stirrer element and a reflux condenser. and sprinkles 2.00 g of magnesium oxide, granulation 0.2-1.0 mm, which has been previously roasted at the temperature of 873 K, one hour in a stream of air and 5 hours in a stream of dry nitrogen. The suspension was stirred and heated to reflux for 4 hours After cooling, the precipitate is filtered, washed three times with 3 cm ^{3 of} 2-propanol and washings were combined the original filtrate. Evaporation of the solution under reduced pressure in a vacuum evaporator gave (E) -t-BuOL with a mass of 3.68 g (94.2% yield) and a purity of 98.5%.

PL 210 088 B1

P r z x l a d II.

(E) -t-BuOL was prepared analogously to example E by stirring and heating to boiling a suspension of 2.00 g of magnesium oxide, granulation 0.05-0.63 mm, in a solution of 3.86 g (0.025 mol) of t-BuON- u in 17.63 g (0.2 mol) of 2-pentanol for 6 hours. The yield of (E) -t-BuOL in this solution is 96.0% (GC). Fractional distillation of this solution yielded pure (E) -t-BuOE (> 98% GC) in an amount of 3.21 g, 82.2% of theory.

P r x l a d III

The process was carried out in the same way as in example 1, stirring and heating to boiling a suspension of 1.00 g of magnesium oxide with a grain size of 0.16-0.4 mm, previously calcined in an air stream at the temperature of 973 K for 4 hours, in a solution of 1.93 g (0.0125 mol) t-BuON in 6 g (0.1 mol) of 2-propanol during 8 hours. After filtering off the catalyst and washing it, a product solution was obtained, the yield of (E) -t-BuOE is 94.2%. Evaporation of the solution under reduced pressure on a vacuum evaporator gave 1.82 g of (E) -t-BuOL with a purity of 98.4%.

P r x l a d IV.

The process was carried out in the same way as in example 1, stirring and heating to boiling a suspension of 4.00 g of magnesium oxide with granulation 0.63-2.5 mm, previously calcined for 4 hours at the temperature of 873 K in a stream of air, in a solution of 7.713 (0.05 mol) t-BuON in 36.0 g (0.6 mol) of 2-propanol within 10 hours. After separation of the catalyst and evaporation of acetone and 2-propanol under reduced pressure, 7.5007 g of crude product was obtained which was purified by distillation under reduced pressure. (E) -t-BuOL was obtained with a purity of 98.7% and a weight of 7.111 g, yield 91.0%.

P r z k ł a d V.

The process was carried out in a glass reactor equipped with a stirring element, a 20 cm long Vigreux glass column and a distillation condenser. Amounts of reagents and catalyst as in Example 4. The process was carried out as in the previous examples with the difference that the resulting acetone was slowly distilled off in a mixture with 2-propanol from the reaction mixture under normal pressure. After 2 hours of distillation, the reaction was stopped and the mixture was separated. After distillation of the crude (E) -t-BuOL, a product was obtained with a mass of 7.235 g and a purity of 97.9%, yield 92.6%.

P r x l a d VI

The process was carried out analogously to example 3 and with the same amounts of reagents and catalyst. After the mixture was heated to reflux and cooled to room temperature, a 10% aqueous solution of sulfuric acid was added dropwise with stirring until the catalyst was dissolved. 20 cm ^{3 of} water was added and the product was extracted with ethyl acetate (3 times 10 cm ³ ). After drying the extract with anhydrous magnesium sulfate and evaporating the solvent, 1.59 g of (E) -t-BuOL was obtained with a purity of 98.0% with a yield of 81.1%.

Example VII

The process was carried out in the same way as in example 1, stirring and heating to boiling a suspension of 0.200 g of magnesium oxide with a grain size of 0.16-0.4 mm, previously calcined in a stream of air at the temperature of 873 K for 6 hours, in a solution of 0.386 g (0.0025 mole) of t-BuON in 1.482 g (0.02 mole) of 2-butanol for 5 hours After filtering off the catalyst and washing it, a product solution was obtained in which the yield of (E) -t-BuOL was 94.5% Evaporation of the solution under reduced pressure in a vacuum evaporator gave 0.353 g of (E) -t-BuOL with a purity of 98.1% with a yield of 90.4%.

Claims (3)

1. Method for the production of (E) -4-t-butylcyclohexanone by reacting 4-t-butylcyclohexanone and a non-standard alcohol, characterized in that the reaction is carried out in a molar ratio of 4-t-butylcyclohexanone to an ordinary alcohol from 12 to 1:12, at the boiling point of the mixture and in the presence of a catalyst, which is magnesium oxide, previously calcined at a temperature of 573-1073 K, in a stream of air or inert gas, for 1 to 10 hours. 2 The method according to claim A process as claimed in claim 1, characterized in that propan-2-ol or butan-2-ol is used as the secondary alcohol. 3. The method according to p. The process of claim 1, characterized in that the magnesium oxide has a granulation of 0.05-2.5 mm.