IT8322538A1 - PROCESS FOR THE PRODUCTION OF KETO-ACIDS OR KETO-ESTERS - Google Patents

Description

Patent Application for Industrial Invention entitled: Process for the production of keto-acids or keto-esters "

Summary

Process for the preparation of -keto-acids or keto-esters of formula

by the carbonyl action of keto-ethers or keto-alcohols, in the presence of water or alcohol, with a catalytic system consisting of metallic Pd, Pd salts or complexes of Pd and HC1.

Can you? operate in a homogeneous or heterogeneous system, but in any case with the reagents in the liquid phase.

Description

The present invention relates to a new process for the production of keto carboxylic acids or their esters.

Pi? precisely the present invention relates to a process for the production on an industrial scale, with high yields of alitatic, arylalytic, alkyl-cycloaliphatic-keto acids or their esters by carbonylation of keto-ethers or keto-alcohols.

It is known that keto acids and their esters, such as levulinic acid and livulinic esters, are raw materials or intermediates of great interest in the chemical industry (Industriai and Engineering Chemistry, vol. 48, N? 8 (1956 ), 1330-1341).

It is known that, despite the great potential importance of these products and their versatility? long recognized, they have never reached a large-scale commercialization stage of their own due to the lack of an industrially viable process for their production.

A specific process for the production of levulinic acid by carbonylation of methyl vinyl ketone in the presence of a catalyst based on Ni (CO). ? was actually? proposed (W. Reppe et al. J. Liebig Annalen Chem., 582 (1953, 38).

However, this process has had no practical use both for the relatively drastic reaction conditions (230 ° C at 100 atm. Of CO pressure) which require high plant costs, and for the low yields (around 25%) and long reaction times (about 16 hours).

Pi? recently (Y. Matsui-Tetr. Lett., 14 (1976), 1107)? Attempted to produce vinyl ketone levulinic acid using Pd-based catalysts,

Rh, Co, Ni, but all attempts in this regard fail

they gave no results.

A production process of

or ({-keto acids or their esters achievable in conditions of relatively mild temperature and pressure, and therefore without excessive plant costs, as well as in short times and with high yields, a process that can?

therefore constitute the solution to the problem of

large-scale, cost-effective production of this attractive product class

The new process object of the present invention

is based on the following reaction ?:

? n.

aryl, al chylaryl, aralkyl cycloalkyl the same or different from each other are H, alkyl

aryl

or and R together with the C atoms to which they are bonded form a cycloaliphatic ring

R 'and R ", equal or different, are H, alkyl

n = integer between 1 and 3.

The new process? based on the carbonylation of an ether or an alcohol in the presence of a catalyst of Pd and of HCl or of an inorganic chloride of the Lewis acid type. The reaction is also carried out in the presence of if it is desired to obtain the free acid or in the presence of an alcohol if it is desired to prepare the corresponding ester.

The reaction requires partial pressures of CO comprised between 10 and 200 atm., Preferably around 100 atm., And temperatures comprised between 50 and 140? C preferably between 100 = and 110 ° C. Under these conditions, the reaction? complete in 1-2 hours.

The conversion of the product, starting? generally of the order of 100%? the selectivity? in acid or linear ester? between -50 and 90%. It is particularly relevant that in the case in which n = 2 or 3 there is practically no formation of the corresponding branched isomeric compounds, the formation of which? always competitiveness? in the production processes of compounds (I). Yes, what is it? a process with regioselectivity? practically of: 100% in linear products.

The starting compounds (II) for the new synthesis are compounds available on the market or easily obtainable by known syntheses or are secondary products in industrial processes and therefore are available at low prices. For example, the? -Hydroxy derivatives having a ketone group in position V can be synthesized by simple condensation of a ketone with formaldehyde (J.H. Singelt et al.? USP 3,989,674). while the corresponding ethers can be easily synthesized by adding an alkanol to the olefin obtainable by dehydration of the? - hydroxy derivative (T.G.Jr. Snapp et.al. USP 3.701.79 8).

The catalyst of Pd pu? be heterogeneous or homogeneous and? preferably selected from the following classes: i) metallic palladium as such or variously supported, ii) palladium salts, iii) coordination complexes of palladium.

In the first case, the metallic palladium can? be conveniently supported on carbon or graphite, as found commercially available without requiring any preliminary treatment. The percentage of supported metal is not critical and can? conveniently be between 1 and 10%. As for this invention, you can? using palladium of any source to prepare the supported catalyst. When it is desired to use a palladium salt, the identity? of the anion of the same not determining, even if? a monovalent anion is preferable. Examples of such anions are: chloride, nitrate, acetate. When it is desired to employ a palladium complex this can be in any oxidation number even though it is preferable in oxidation number 2. How anion? chloride is preferable.

As a binder? It is convenient to use an organic compound having at least 3 carbon atoms and containing an element of the Va or VIa group, preferably phosphorus, arsenic, antimony or bismuth in a valence 3 state. Of these, phosphorus compounds are preferable. In general, the ligands can be represented by the formula MR where M represents phosphorus, arsenic, antimony, trivalent bismuth and R represents the same or different aryl, cycloaliphatic alkyl groups having preferably from 1 to 20 carbon atoms

Examples of such radicals are methyl, ethyl, butyl, cyclohexyl, phenyl, tolyl, and the like. A triaryl ligand, for example triphenyl, is preferable.

Examples of ligands useful in the process of the present invention are: trimetriphosphine, triethylphosphine, triphenylphosphine and analogues of arsenic, antimony and bismuth. Between these ? preferable to use triphenylphosphine. Palladium can? be complexed to the ligand before being introduced into the reaction medium or the complex can? be formed "in situ" by simply adding a palladium salt and ligand directly to the reaction medium. In both cases ? It is preferable to add the binder to the metal salt in the binder / metal ratio between 0, 5 and 5, preferably between 2 and 3.

It should be noted that when the aforementioned palladium salts or its complexes are used with the MR3 ligands, the formation of metallic palladium is always noted. however, among the purposes of the present invention to specify the nature of the catalytically active species and whether these act in a homogeneous or heterogeneous phase.

The most? convenient for carrying out the process according to the present invention provides for the use of metallic Pd supported on activated carbon and of HCl. Hydrochloric acid can? be added to the reaction medium as a gas or in an aqueous solution.

Practically ? it is preferable to use gaseous HCl dissolved in the alkanol if you want to synthesize an ester or aqueous HCl when you want to synthesize an acid.

Among the chlorides that can be used in place of HCl, the pi? cheap ? AlCI. The reaction of the present invention? conducted in the liquid phase - in which the catalyst is dissolved or suspended. The liquid reaction medium can? be based on an alkanol, which then also functions as a reagent in the synthesis of esters, or on a suitable solvent whose choice depends on the product to be synthesized.

If you want to synthesize; a keto acid the solvent. to prefer? an organic acid Examples of such acids are: formic, acetic, propionic, butyric, isobutyric acid, etc. Acetic acid is preferred. Should you wish to synthesize a keto ester, the preferred solvent? the same reagent alkanol, or another solvent selected from the classes of hydrocarbons, ketones, halogen derivatives, for example hexane, benzene, toluene, xylene, acetone, methyl ethyl ketone, diethyl ketone, chloroform, chlorine benzene.

The presence of small quantities? water does not substantially alter the yield in the keto esters therefore? the use of anhydrous reaction medium is not necessary.

The process of the present invention can? be made under carbon monoxide pressure even of a few atmospheres. Pu? also be used

carbon monoxide not pure, mixed with other gases, as long as? these are substantially inert in the reaction conditions. For example, carbon monoxide can? contain nitrogen, CO2, noble gases, methane or other aliphatic hydrocarbons.

Better to avoid the presence of quantity? relatively considerable oxygen that can? give side reactions.

The pressure of carbon monoxide can? conveniently varying between 10 and 200 atmospheres; preferably it operates around 100 atm. At the most pressures? low yields are significantly lower; the yield does not significantly improve by using very high carbon monoxide pressures.

The process ? achievable. Under relatively mild temperature conditions, conveniently between 50 and 140 ° C, preferably between 100 and 110 ° C.

It has been found that by operating at lower temperatures the speed? of the carbonylation nm? completely satisfactory, while above 110 ° C increases the formation of unwanted products.

The reaction time is not? critic. Was that the reaction found? generally complete after 1-2 hours operating at 110 ° C, under a carbon monoxide pressure of 100 atmospheres. Extending the time of. reaction, no substantial variation in the desired product yield is noted.

The quantities Relatives of reactants, catalyst and solvent can vary over very wide ranges. It has been found that the best results are obtained by using the various chemically active species in approximately the following molar ratios: substrate to be carbonylated: R "OH: catalyst: HC1 = 1 = 1: 2 .: 0.001: 3.

When it is desired to obtain the ester and it is desired to use the same reagent alcohol also as a solvent,? It is convenient to use a substrate: alkanol ratio between about 1: 1 and about 1:

10 by volume. When do you want to synthesize acid? it is convenient to use a solution of about 1 M in substrate to be carbonylated.

The process can? be conducted both continuously and discontinuously. In the second case, the catalyst and the reactants are added to the reaction medium and the whole is introduced into the reaction zone where they are pressurized with carbon monoxide and brought to the desired temperature.

When the process is carried out continuously, the reaction medium containing the reactants and the catalyst, if homogeneous, is carried out in con? continuous to the reaction zone, where instead the catalyst is predisposed if heterogeneous. The reaction zone is then continuously pressurized with carbon monoxide. The gaseous reactants can escape as a separate effluent from the liquid effluent from which to recover the desired products by conventional methods, such as distillation.

The process according to the present invention is further illustrated hereinafter by the following examples. The reported operating conditions must be intended exclusively as a non-limiting example of the invention itself.

Example 1

11 mg of-Pd / C at 10% of Pd, 1.2 ml of 4-ethoxy-2-butanone (9.2 mmoles), 9 ml of ethyl alcohol-containing HCl in solution (3.1 M), are placed in a pyrex glass bottle and this is introduced an autoclave.

The autoclave is purged with CO and then pressurized with the same at 100 atm. at room temperature.

The mixture is reacted for 2 hours at 110 ° C. The yield in ethyl levulinate? 92%.

Example 2

The catalyst used in example 1, recovered by centrifugation, washed with ethanol and dried, is reused in a new test carried out under the same conditions as example 1.

The yield of ethyl levulinate? 75%.

Example 3

The procedure of example 1? repeated using as catalyst trans-PdCl (PPh) in quantity? of 0.25 - 10 moles.

The yield of ethyl levulinate is 94%.

Example 4

The procedure of Example 1 was repeated, using PdC12 as catalyst in a quantity of of 0.25 <. > 10 moles. The surrender? 95%.

Example 5

1.25 ml of 4-hydroxy-2-butanone, 2 ml of 37% aqueous HCl, 6.5 ml of glacial acetic acid and 22 mg of Pd / C are reacted under the same conditions described in the example? 1.

After 2 hours the yield in levulinic acid? 74%.

Example 6

Under the identical conditions of example 1, 5-ethoxy-3-butanone is carbonylated.

You get the product

with a yield of 93%.

R i v e n d i c a z i o n i 1. Process, for the production of formula products.

(THE)

wherein R alkyl aryl, alkylaryl, aralkyl, cycloalkyl; -

equal or different from each other are H,

aryl alkyl

or R and R1 together with the atoms of C on which they are bound form a cycloaliphatic ring

R "? H or alkyl

n = integer number between 1 and 3 characterized in that a compound of formula wherein is reacted

n are defined as above and R '= H or alkyl

with

/ carbon monoxide, in the presence of a catalyst of Pd and hydrochloric acid or a clo

inorganic ride, in a liquid medium consisting of o

comprising the compound of formula R "OH, wherein

R "is as defined above.

2. Process according to claim 1, wherein the

reaction takes place under CO pressure

between 10 and 200 atm. , at temperatures between 50 and 140 ° C.

1.. Process according to claim 2, in which the reaction takes place under CO pressure around 100 atm. , at temperatures between 100 and 110 ° C.

4. Process according to claim 1, wherein the Pd catalyst? selected from the group consisting of free or supported metallic Pd, palladium salts, coordination complexes of Pd.

5. Process according to claim 1, wherein the? HCl? added to the reaction medium in the form of an aqueous or alcoholic solution.

6. Process according to claim 1, wherein the liquid reaction medium also comprises a carboxylic acid

7. Process according to claim 1, wherein the liquid reaction medium also comprises an organic solvent selected from the classes of aliphatic and aromatic hydrocarbons, alitatic ketones, halogenated aliphatic or aromatic hydrocarbons.

8. Process according to claim 1, wherein the CO? used in mixture with other inert gases under the reaction conditions.