PL218743B1 - Process for the preparation of unsaturated ketones - Google Patents

Description

Description of the invention

The subject of the invention is a method of obtaining α, β- and β, γ-unsaturated ketones, which, due to their characteristic and very persistent smell, are used in the cosmetics and perfumery industry.

Unsaturated ketones can be prepared using an aldol condensation reaction. This reaction usually takes place in an alkaline environment.

There is known a method of producing 1- (1-cyclohexen-1-yl) propan-2-one [Yoshioka et. all. Bull. Chem. Soc. Jpn .; 1972; 45; 636-638]. The authors of the publication performed a condensation reaction between cyclohexanone and acetone in alkaline medium, catalyzed with sodium ethoxide, at a temperature (-50 ° C) in toluene. In this reaction, the hydroxyketone was formed in a yield of 32.6%. The authors then subjected the hydroxyketone to a dehydration reaction in the presence of p-toluenesulfonic acid in benzene to obtain α, β- and β, γ- unsaturated ketones.

The applied principle - sodium ethoxide is an unstable compound which, under the influence of moisture, hydrolyzes to sodium hydroxide and ethanol, which causes difficulties in storage and the need to prepare immediately before the reaction. The same problem applies to other alkoxides used as aldol condensation catalysts. Moreover, the yields of the products of the above reactions were not satisfactory. Condensation of acetone and cyclohexanone in sodium ethoxide at a temperature of (-50 ° C) led to the formation of a 2,6-dihydroxy-2,6-dimethylheptan-4-one byproduct formed in the acetone self-condensation reaction. Benzene used in dehydration is currently not used due to its carcinogenic effect.

The essence of the invention is a process for the preparation of unsaturated ketones of general formula 1

where R1, R2 are alkyl, or of the general formula 2

wherein R1, R2 are as above in which the aldol condensation followed by the dehydration of the hydroxy ketones obtained by aldol condensation is carried out. The aldol condensation reaction is carried out in such a way that the organic solvent is mixed with the base and cooled to a temperature (-70 - (- 45 ° C)), then a ketone or a mixture of two ketones of formula 3 is added dropwise to the mixture.

where R3, R4 are alkyl, cyclic alkyl, or hydrogen.

PL 218 743 B1

The resulting hydroxy ketones are dehydrated by heating in an organic solvent in the presence of an acid. Potassium t-butoxide is used as the base in the aldol condensation reaction.

Preferably, toluene is used as the organic solvent in the aldol condensation reaction.

Preferably the reaction is carried out at a temperature (-60 - (-55 ° C)).

Preferably, dichloromethane is used as the solvent in the dehydration reaction.

The potassium tert-butoxide used in the presented process is a strong, relatively stable base, with low hygroscopicity, so it can be used in conditions of natural air humidity. Moreover, it is a commercially available product, which means that it does not need to be prepared before the reaction. The reduction of the condensation temperature caused both the reduction of the amount of the by-product formed and the increase of the reaction efficiency by approx. 10%. The use of dichloromethane as a solvent is safe for health, in contrast to the benzene used in the prior art. In addition, changing the solvent from benzene to dichloromethane allowed the reaction temperature to be lowered without reducing its yield.

The following examples illustrate the invention.

P r z k ł a d 1

Autocondensation of butan-2-one

A three-neck round bottom flask with a capacity of 500 ml was placed in a cooling bath (ethanol + liquid nitrogen), suitable for stirring with an efficient magnetic stirrer. The cooling bath was able to reach temperatures down to -65 ° C inside the reaction flask. The flask was equipped with a pressure equalizing dropping funnel with a capacity of 150 ml, a thermometer for measuring temperatures down to -100 ° C and a tip supplying dry argon. A suspension of potassium t-butoxide (47.20 g; 0.39 mol) in toluene (250 mL) was prepared in a reaction flask. Toluene was distilled and stored over sodium metal before being used in the reaction. Butan-2-one (103.00 g, 1.43 mol) was placed in the dropping funnel. The butan-2-one was distilled before being used in the reaction and additionally dried using 4A molecular sieves. The flask containing the potassium t-butoxide suspension in toluene was cooled to -60 ° C and the dropwise addition of 2-butanone was started while stirring with a magnetic stirrer. The ketone addition rate depended on maintaining a constant temperature of the reaction mixture within the range of -60 to -55 ° C. The total dripping time of the ketone was about 20 to 30 minutes. After complete addition of the butan-2-one, stirring was continued for 1 h at a temperature of about -60 to -55 ° C. The cold mixture was poured into a beaker containing 470 g of crushed ice and 58 ml of concentrated hydrochloric acid, and left for 1 hour. at 0 ° C. After this time, the beaker with the mixture was left at room temperature for 1-2 hours. In a manifold with a capacity of 2000 mL was separated the toluene layer and the aqueous layer was extracted three times with diethyl ether (3 x 30 mL). The ether extracts were combined with the toluene layer, washed with saturated sodium chloride solution (3 x 30 ml), and then dried over anhydrous magnesium sulfate. Ether and toluene were distilled off on a rotary evaporator and the remaining liquid was distilled under reduced pressure.

The distillation was performed twice.

First distillation (3-4 mm Hg): fraction 1: 40-43 ° C (9.29 g; 9.21%); fraction 2: 46-45 ° C (10.74 g; 10.65%); fraction 3: 46.5-48 ° C (10.41 g; 10.33%); fraction 4: 49-50 ° C (1.08 g; 1.07%)

Fractions Nos. 1, 2, 3, 4 were combined and the distillation was repeated.

2nd distillation (2mm Hg); fraction 1: 27 ° C (3.03 g; 3%); fraction 2: 33-36 ° C (10.73 g; 10.64%); fraction 3: 36-36.5 ° C (11.53 g; 11.43%); fraction 4: 36.5-38 ° C (4.7 g; 4.66%). Fraction 1 was discarded and fractions 2, 3 and 4 were combined to give 26.96 g (27%) of the hydroxy ketone (5-Hydroxy-5-methylheptan-3-one) as a colorless oil with a characteristic odor.

Dehydration of hydroxyketone (5-Hydroxy-5-methylheptan-3-one) preparation of a mixture of unsaturated ketone isomers 5-Hydroxy-5-methylheptan-3-one (2) (14.27 g, 0.1 mol), dried and distilled chloride methylene (60 ml), p-toluenesulfonic acid (1.0 g, 5 mmol) was placed in a 100 ml round bottom flask equipped with a reflux condenser and an azeotrope head. The reaction mixture was heated on a heating mantle for 8 hours while stirring with a magnetic stirrer. The resulting dark red solution was cooled to room temperature, washed three times in a 100 ml separating funnel with distilled water (3 times 20 ml), dried over anhydrous magnesium sulfate. The solvent was evaporated and the remaining liquid was distilled in the apparatus under reduced pressure, collecting the fraction boiling at 21-22 ° C.

PL 218 743 B1 at 2 mm Hg. 8.25 g (66%) of a mixture of unsaturated ketones were obtained in the form of a colorless liquid with a characteristic odor.

P r z k ł a d 2

Condensation between acetone and cyclohexanone

A three-neck round bottom flask with a capacity of 500 ml was placed in a cooling bath (ethanol + liquid nitrogen), suitable for stirring with an efficient magnetic stirrer. The cooling bath was able to reach temperatures down to -65 ° C inside the reaction flask. The flask was equipped with a pressure equalizing dropping funnel with a capacity of 150 ml, a thermometer for measuring temperatures down to -100 ° C and a tip supplying dry argon. A slurry of potassium t-butoxide (35 g; 0.31 mol) in toluene (250 mL) was prepared in a reaction flask. Toluene was distilled and stored over sodium metal before being used in the reaction. The dropping funnel was charged with acetone (30.16 g; 0.52 mol) and cyclohexanone (50.00 g; 0.510 mol). The ketones were distilled before being used in the reaction and additionally dried using molecular sieves (4A). The flask containing the potassium t-butoxide suspension in toluene was cooled to -60 ° C and the ketone mixture was added dropwise with stirring with a magnetic stirrer. The dropping rate depended on keeping the temperature of the reaction mixture constant in the range of -60 to -55 ° C. The total dropwise time of the ketone mixture was about 20 to 30 minutes. After complete dropwise addition of the ketones, stirring was continued for 1 h at about -60 to -55 ° C. The cold mixture was poured into a beaker containing 350 g of crushed ice and 43 ml of concentrated hydrochloric acid, and left for 1 hour. at 0 ° C. After this time, the beaker with the mixture was left at room temperature for 1-2 hours.

In a manifold with a capacity of 2000 mL was separated the toluene layer and the aqueous layer was extracted three times with diethyl ether (3 x 30 mL). The ether extracts were combined with the toluene layer, washed with saturated sodium chloride solution (3 x 30 ml), and then dried over anhydrous magnesium sulfate. Ether and toluene were distilled off on a rotary evaporator and the remaining liquid was distilled under reduced pressure.

Distillation Results:

78-82 ° C at 1-2 mm Hg

29.84 g (39.5%) of the hydroxy ketone was obtained in the form of a colorless oil.

Claims (4)

A method for the preparation of unsaturated ketones of the general formula I where R1, R2 are alkyl, or of the general formula 2 where R1, R2 are as above, in which an aldol condensation followed by dehydration of hydroxyketones obtained by aldol condensation is carried out, wherein an aldol condensation reaction is carried out in such a way that the organic solvent is agitated The ketone or a mixture of two ketones of formula III is added dropwise to the mixture, where R3, R4 are alkyl, cyclic alkyl or hydrogen atom, and the hydroxy ketones obtained as a result of the reaction are subjected to the reaction. dehydration by heating in an organic solvent in the presence of an acid, characterized in that potassium ί-butoxide is used as the base in the aldol condensation reaction and the reaction is carried out at a temperature (-70- (-45 ° C)). 2. The method according to p. The process of claim 1, wherein the reaction is carried out at a temperature (-60 - (- 55 ° C)). 3. The method according to p. The process of claim 1, wherein the organic solvent is toluene in the aldol condensation reaction. 4. The method according to p. The process of claim 1, wherein the organic solvent is dichloromethane in the dehydration reaction.