GB2119362A

GB2119362A - Process for producing ketones

Info

Publication number: GB2119362A
Application number: GB08209293A
Authority: GB
Inventors: Zdenek Mazour; Paul Radimerski
Original assignee: Ciba Geigy AG
Current assignee: Novartis AG
Priority date: 1982-03-30
Filing date: 1982-03-30
Publication date: 1983-11-16

Abstract

There is described a process for producing ketones of the formula I <IMAGE> by oxidation of an alcohol of the formula II <IMAGE> with chlorine in a two-phase reaction medium consisting of water and an organic solvent immiscible with water, the pH-value during the reaction being kept between 1 and 7 by the addition of alkali metal or alkaline-earth metal hydroxide solution. In the formulae I and II, R1 and R2 independently of one another are each C1-C10-alkyl, alkoxyalkyl having at most 12 carbon atoms, or phenyl which is unsubstituted or is substituted by halogen or C1-C6-alkyl, or R1 and R2 together form a C4-C10-alkylene chain.

Description

SPECIFICATION Process for producing Ketones The present invention relates to a novel process for producing ketones of the formula I

wherein R1 and R2 independently of one another are each C1-C10- alkyl, alkoxyalkyl having at most 12 carbon atoms, or phenyl which is unsubstituted or is substituted by halogen or C1-C6-alkyl; or wherein R1 and R2 together can also form a C4-C10-alkylene chain.

The compounds of the formula I are produced by oxidation of secondary alcohols of the formula II

wherein R1 and R2 have the meanings given under the formula I, with free chlorine, in which process chlorine is added at 0 to 100 C to a solution of the alcohol of the formula II in an inert solvent immiscible with water, a pH-value of 1 to 7 being maintained in the reaction mixture by adding an aqueous solution of an alkali metal hydroxide or alkaline-earth metal hydroxide during the addition of chlorine.

Some of the ketones of the formula I are products which are produced on a large commercial scale.

Examples of these are: acetone and ethyl methyl ketone, which are used as solvents; benzophenone, which serves as an intermediate in the production of antihistamines, insecticides or hypnotics; and cyclohexanone, which is known both as a solent and as an intermediate in the manufacture of nylon.

l-Methoxy-2-propanone is of particular importance as an intermediate for Metolachlor. Metolachlor, the production and action of which are known from the U.S. Patent Specification No. 3,937,730 and from the German Auslegeschrift No. 2,328,340, has proved to be a highly active and selective herbicide in various types of cultivated crops.

Several processes for the oxidation of secondary alcohols to ketones using halogen complexes or hypohalides are described in the literature. Such references are: Tetrahedron Lett. 1973, 919-922; Tetrahedron Lett. 1974, 3059-3062; Tetrahedron Lett. 1976, 1641-1644; Polish Patent Specification No. 97 822; Synthesis 1976, 811-813; U.S. Patent Specification No.3,996,259; and J. Org. Chem. 1980, 2030-2032.

The processes described are not satisfactory for application as commercial processes; this is because on the one hand the solvents and chemicals used are in part ecologically undesirable and the product yield is in some cases low, and because on the other hand the volume of solvent required is high and the resulting volume yield consequently low.

There was therefore a need for an oxidation process applicable on a commercial scale, which firstly would be satisfactory from an ecological standpoint, that is to say, would not result in unsafe waste products being produced and would render possible the recycling of solvents, and secondly would economically attain a high product yield by virtue of a small reaction volume. The present invention provides such an oxidation process for producing ketones from secondary alcohols.

It is suggested according to the present invention that the oxidation of a secondary alcohol of the formula II to the ketone of the formula I be performed with chlorine in a two-phase reaction medium, which consists of water and an inert organic solvent immiscible with water, at temperatures of between 0 and 100 C, the pH-value being maintained between 1 and 7 during the entire course of the reaction.

Suitable organic solvents are not miscible with water and are not capable of being chlorinated under the above reaction conditions, for example chlorinated hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride or chlorobenzene.

The reaction medium is maintained according to the invention acidic during the entire duration of the reaction. It has been shown that preferably the pH-value is to be kept between 1 and 7, especially between 3 and 4. A suitable method of regulating the pH-value is to add measured amounts of an aqueous solution of an alkali metal or alkaline-earth metal hydroxide. Suitable alkali metal or alkaline-earth metal hydroxides are for example sodium, potassium, magnesium and calcium hydroxide.

The chlorine used as oxidising agent is usually introduced in gaseous form into the reaction vessel, the chlorine being preferably passed directly into the liquid reaction mixture.

The rate of introduction of the chlorine gas and of the alkali metal hydroxide solution is dependent on the cooling capacity of the reaction vessel.

The temperature during the reaction is kept between 0 C and the boiling point of the solvent; generally it is kept below 100"C. A preferred reaction temperture is between 0 and 50"C, particularly between 5 and 40"C.

It is advantageous for the suggested reaction to add a phase-transfer catalyst. The amount of catalyst can vary within wide limits, for example from 0 to 50 ml % of the alcohol used. Catalyst concentrations of 1 to 10 mol % are preferred. The rate of reaction, the yield and the selectivity can be simultaneously increased by the addition of the catalyst. Furthermore, the selectivity of the reaction is improved by the exclusion of light.

Suitable phase-transfer catalysts are quaternary ammonium salts, such as butylpyridinium bromide, triethylbenzylammonium bromide or -chloride, trimethylbenzylammonium chloride, triethylhexadecylammonium bromide or -chloride, trimethylhexadecylammonium bromide or chloride, dibutyldimethylammonium chloride, triethyldecylammonium bromide, methyltrinonylammonium chloride, methyltriphenylammonium bromide, tetrabutylammonium bromide or -chloride and trioctylmethylammonium chloride; quaternary phosphonium salts, such as hexadecyltrimethylphosphonium bromide, hexadecyltributylphosphonium chloride, tetraphenylphosphonium bromide or -chloride and tetrabutylphosphonium chloride, and also crown ethers, such as 18-crown-6, dibenzo-18-crown-6 and dicyclohexyl-18-crown-6.

The time required for performing the oxidation reaction to effect the complete conversion can be up to 100 hours. Very much shorter reaction times can be obtained by an intensive cooling of the reaction medium.

Preferably, however, a reaction time of 24 hours is not exceeded.

The products of the formula I are isolated from the reaction mixtures by separating the precipitated alkali metal or alkaline-earth metal chlorides by filtration, centrifuging or sedimentation; the organic phase is then processed by distillation, and the inorganic phase by extraction and subsequent distillation of the organic extracts. In some cases, a portion of the product of the formula I can also be obtained directly, by distillation from the aqueous phase, as an azeotropic mixture with water.

A preferred embodiment of the process according to the invention comprises mixing the alcohol of the formula II together with 1 to 10 mol % of a phase-transfer catalyst in methylene chloride in a darkened apparatus; introducing chlorine, with vigorous stirring, directly into the solution at 20 to 250C, and adding 30% sodium hydroxide solution in such a manner that the pH-value of the reaction mixture is maintained between 3 and 4.

The process according to the invention is further illustrated by the Examples which follow: Example 1: Acetone 87 g (1.22 mols) of chlorine are introduced below the surface at 20 to 25"C, with stirring and the exclusion of light, into a solution of 60 g (1 mol) of isopropanol and 5 g (0.022 mol) of triethylbenzylammonium chloride in 100 ml of chlorobenzene in the course of 5 hours. During this period of time, the pH-value of the mixture is kept at 3 to 4 by the slow addition of 266 g of 30% (1.99 mols) of sodium hydroxide solution. At the end of the introduction of chlorine, the reaction mixture contains no further isopropanol. The reaction mixture is neutralised by adding a small amount of sodium hydroxide solution.After the sodium chloride which has precipitated has been filtered off, the organic phase is separated, the aqueous phase is extracted 3 times with 50 ml of chlorobenzene each time, and the combined organic phases are fractionally distilled to thus yield 54.5 g (94%) of acetone.

Example 2: Acetone Into a solution of 60 g (1 mol) of isopropanol in 100 ml of chlorobenzene are introduced at 20 to 25"C below the surface, with stirring and the exclusion of light, 75 g (1.06 mols) of chlorine within 5 hours. During this time, the pH-value of the mixture is kept at 3 to 4 by slowly adding 252.7 g (1.9 mols) of 30% sodium hydroxide solution. After conclusion of the introduction of chlorine, the reaction mixture contains no futher isopropanol. Further processing is carried out in a manner analogous to that of Example 1 to thus obtain 52 g (89.7%) of acetone.

Example 3: Cyclohexanone 45 g (0.63 mol) of chlorine are introduced at 20 to 25"C below the surface, with stirring and the exclusion of light, into a solution of 50 g (0.5 mol) of cyclohexanol and 2.5 g (0.011 mol) of triethylbenzylammonium chloride in 50 ml of methylene chloride in the course of 6 hours. During this period of time, the pH-value of the mixture is maintained constant at 3 to 4 by the slow addition of 153 g (1.14 mols) of 30% sodium hydroxide solution. The reaction mixture contains no further cyclohexanol at the end of the introduction of chlorine. The reaction mixture is then neutralised by adding a small amount of sodium hydroxide solution.

After the sodium chloride which has precipitated has been filtered off, the organic phase is separated, the aqueous phase is extracted 3 times with 20 ml of methylene chloride each time, and the combined organic phases are fractionally distilled to thus yield 45.4 g (92.6%) of cyclohexanone.

Example 4: Benzophenone 20 g (0.28 mol) of chlorine are introduced at 200 to 250C below the surface, with stirring and the exclusion of light, into a solution of 46 g (0.25 mol) of diphenylcarbinoi and 1.25 g (0.0055 mol) of triethylbenzylammonium chloride in 100 ml of methylene chloride in the course of 4 hours. During this period of time, the pH-value of the mixture is kept constant at 3 to 4 by the slow addition of 66.5 g (0.5 mol) of 30% sodium hydroxide solution. The reaction mixture contains no further diphenylcarbinol after conclusion of the introduction of chlorine.After removal by filtration of the sodium chloride which has precipitated, the organic phase is separated, the aqueous phase is extracted twice with 50 ml of methylene chloride each time, and the combined organic phases are concentrated by evaporation to thus obtain 45 g (99.5%) of benzophenone.

Example 5:1-Me th ox y-2-propan one 230 g (3.24 mols) of chlorine are introduced at 20 to 25"C below the surface, with stirring and the exclusion of light, into a solution of 270 g (3 mols) of 1 -methoxy-2-propanol ad 15 g (0.0363 mol) of trioctylmethylammonium chloride in 300 ml of methylene chloride in the course of 6 hours. During this period of time, the pH-value of the mixture is kept constant at 3 to 4 by the slow addition of 838 g (6.28 mols) of 30% sodium hydroxide solution. After conclusion of the introduction of chlorine, the reaction mixture contains no further 1-methoxy-2-propanol. The reaction mixture is then neutralised by adding a small amount of sodium hydroxide solution.After the sodium chloride which has precipitated has been filtered off, the organic phase is separated, the aqueous phase is extracted 5 times with 50 ml of methylene chloride each time, and the combined organic phases are fractionally distilled to thus yield 250.9 g (95%) of 1 -methoxy-2-propanone.

In place of the extraction of the aqueous phase with an organic solvent, the 1-methoxy-2-propanone contained therein can be obtained also by direct distillation from the aqueous phase as a 70% azeotrope.

Example 6: 1-Methoxy-2-propanone 225 g (3.17 mols) of chlorine are introduced at 30 C below the surface, with stirring and the exclusion of light, into a solution of 270 g (3 mols) of 1-methoxy-2-propanol in 300 ml of methylene chloride within 7 hours. The pH-value during this time is kept constant at 3 to 4 by the slow addition of 811.3 g (6.08 mols) of 30% sodium hydroxide solution. The reaction mixture contains no further 1-methoxy-2-propanol after conclusion of the introduction of chlorine. Further processing is carried out in a manner analogous to that of Example 5 to thus obtain 232 g (88%) of 1-methoxy-2-propanone.

Claims

1. A process for producing ketones of the formula I

wherein R1 and R2 independently of one another are each C1-C10-alkyl, alkoxyalkyl having at most 12 carbon atoms, or phenyl which is unsubstituted or is substituted by halogen or C1-C6-alkyl; or wherein R1 and R2 together form a C4-C10-alkylene chain, by oxidation of secondary alcohols of the formula II

wherein R1 and B2 have the meanings defined under the formula I, with free chlorine, in which process chlorine is added at 0 to 1000C to a solution of the alcohol of the formula II in an inert solvent immiscible with water, a pH-value of 1 to 7 being maintained in the reaction mixture by adding an aqueous solution of an alkali metal hydroxide or alkaline-earth metal hydroxide during the addition of chlorine.

2. A process according to Claim 1, wherein the inert solvent is methylene chloride, chloroform, carbon tetrachloride or chlorobenzene.

3. A process according to Claim 1, wherein the reaction temperature isO to 50"C.

4. A process according to Claim 3, wherein the reaction temperature is 5 to 40"C.

5. A process according to Claim 1, wherein aqueous sodium hydroxide solution is added.

6. A process according to Claim 1, wherein the pH-value is kept between 3 and 4.

7. A process according to Claim 1, wherein a phase-transfer catalyst is used.

8. A process according to Claim 1, wherein the chlorine gas is introduced directly into the liquid reaction mixture.

9. A process according to Claim 1, wherein the alcohol of the formula II is mixed together with 1 to 10 mol % of a phase-transfer catalyst; chlorine is subsequently introduced, with vigorous stirring, directly into the solution at 20 to 25 C, and 30% sodium hydroxide solution is added in such a manner that the pH-value of the reaction mixture is maintained between 3 and 4.

10. A process according to Claim 1 for producing acetone, 2-butanone, cyclohexanone or benzophenone.

11. A process according to Claim 1 for producing 1-methoxy-2-propanone.

12. A process for producing ketones of formula I substantially as described with reference to any of the Examples.

13. A ketone when produced by a process claimed in any of the preceding claims.