HUT74481A - Method for preparing of mono or di-2-substituted cyclopentanone and intermedier - Google Patents

Description

The present invention relates to a process for the preparation of cyclopentanone mono- or disubstituted in the 2-position. More particularly, the present invention relates to the preparation of 2,2-dimethylcyclopentanone.

Cycloalkanones, such as 2-position mono- or disubstituted cyclopentanones, are useful as intermediates in the synthesis of benzylidene azolylmethylcycloalkane fungicides, which are described in particular in EP-A-0 378 953.

Although many methods for the preparation of cyclopentanones mono or disubstituted at the 2-position are known in the art, see, in particular, J. Am. Chem. Soc., 60, 2416-2419 (1938); Bull. acad. Sci. URSS, Classe sci. chim., (29-40), 489-493 (1947) and CA 42 4536d; J. Org. Chem., 25, 1841-1844 (1960); J. Am. Chem. Soc. 102 (1). 190-197 (1980);

Organometallics, 7 (4), 936-934 (1988)], there is a real need for a process which allows the production of cyclopentanone from well-readily available and inexpensive starting materials with good yield. 83546-3035B-KY / KmO. , while on an industrial scale the operation is easy without complicated equipment.

The present invention has been found to meet this requirement.

The present invention thus relates to the preparation of a cyclopentanone, mono- or disubstituted at the 2-position of formula (I), wherein

R ¹ is hydrogen or straight or branched,

- a C 4 alkyl or alkoxy group, or a group of formula (R ² ) p-above I - (- CR ³ R ⁴ -) q, wherein

R ² is a straight or branched C 1 -C 3 alkyl group,

R ³ and R ^{4 are the} same or different and are hydrogen or straight or branched C 1 -C 3 alkyl, p and q are the same or different from 0 to 3.

The process is carried out by sequentially carrying out four steps (a) to (d), which may be carried out sequentially in the same reactor as needed:

- Step (a) consisting of:

* (j is reacted with an optionally substituted 2-substituted 1,3-butadiene of formula II wherein R ¹ is as defined above wherein X is R ⁶ or OR ⁶ and R ⁵ and R ^{6 are the} same or different and are linear or branched C 1 -C 6 alkyl groups and this reaction is carried out in an aqueous medium in the presence of a catalyst consisting of at least one water-soluble phosphine and at least one rhodium compound,

to obtain the product of formula (IV) wherein R ¹ , R ⁵ and X are as defined above, then (a ₂ ) isolating the compound of formula (IV) in the organic phase and separating the organic phase from the aqueous phase containing the catalyst settling and, if appropriate, purifying the product by extraction with a suitable solvent and / or distillation;

- (b) the product of formula (IV) is used as a crude product or as a pure product from the organic phase from step (a) ₂ above, and (b) the compound of formula (IV) wherein X is R ⁶ (i) deacylation in a known manner using an alcoholic solution of the alkali metal alkoxide used to prepare the compound of formula (V) wherein R ¹ and R ⁵ are as defined above, (b ₁₂ ) this reaction is followed by alkaline hydrolysis of the ester group COOR ⁵ ; acidification! a reaction which is carried out in a known manner in the same reaction medium to afford the product of formula (VI) wherein R ¹ is as defined for the compound of formula (I);

* (b'i) in the case where X is a compound of formula IV containing OR ⁶ , this compound (b'n) is subjected to the basic hydrolysis of the esters COOR ⁵ and C00 R ⁶ ,

(b'i. ₂ ) this reaction is followed by heat decarboxylation of one of the resulting carboxylate groups followed by acidification! The reaction is carried out in a manner known per se for the preparation of the compound of the formula VI, wherein R ¹ is as defined for the compound of the formula I and then (b ₂ ) the product, i.e. the monocarboxylic acid of the formula VI. isolating it in the aqueous phase, separating the latter from the organic phase and, if appropriate, purifying the product by extraction with a suitable solvent;

- (c) the acid of formula (VI) is used as a crude product from the aqueous phase from reaction (b ₂ ) above or in pure form and * (c,) in a first variant, this compound is hydroxycarbonylated with formic acid such as water and Using a CO medium and using a strong inorganic or organic acid as a catalyst to give the product of Formula VII, wherein R ¹ is as defined above, * (c'i) this compound is optionally hydroxycarbonylated directly using CO gas At a pressure of 1 MPa to 10 MPa CO and using water as a catalyst, a strong inorganic or organic acid is used to prepare the compound of Formula VII, wherein R ¹ is as defined in Formula I, and * (c ₂ ) the product, i.e. The dicarboxylic acid of formula (VII) is isolated by precipitating the compound by adding water to the reaction medium and optionally purified by recrystallization;

· · · · ····· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·–– ·

- (d) the dicarboxylic acid of formula (VII), which is taken from the crude product obtained by precipitation in step (c ₂ ) above, or a pure product, and * (dO is first subjected to a cyclization-decarboxylation reaction by converting the diacid into a cyclic anhydride by reaction with a lower carboxylic acid aldehyde which loses carbon dioxide during the reaction to give the desired cyclopentanone of formula (I);

* (d) this compound is subjected to a cyclization-decarboxylation reaction according to the second variant by pyrolyzing the diacid in a liquid or gas phase in the presence of a catalyst which may be metal or metalloid or a derivative thereof, wherein the element may be: Rb , Cs, V, Mo, B, Al, Ga, In, TI, Sn, Sb or Bi, or (2i) phosphoric acid derivative, wherein the acid may be condensed or non-condensed, the protons of which are substituted with a metal cation other than metal or metalloid in item (i), or ammonium substituted by a cation, to give the desired cyclopentanone of formula (I), and * (d _{2) of} the product isolated in an appropriate manner.

In addition to hydrogen, R ¹ may be, for example, methyl, ethyl, n-propyl, isopropyl, η-butyl, isobutyl or tert-butyl, and the corresponding alkoxy, phenyl, ortho, meth or para-group. tolyl, xylyl and benzyl.

• · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

- 6 ^R5 and ^R6 is preferably methyl, ethyl, η-propyl, isopropyl, η-butyl, isobutyl or tert-butyl. Preferably R ^{1 is} methyl, while R ⁵ and R ⁶ may be the same or different and may be methyl or ethyl.

In step (a) of the process according to the invention, there is the question of the addition reaction on carbon 4 of 1,3-butadiene, optionally substituted on carbon 2, wherein a compound containing an active methylene group of formula III is added. . This reaction is carried out in a manner known per se, as described in EP-A-0 044 771, which allows the addition of a compound of formula IV, which is essentially a mixture of the following two isomers: (IV isomer 1) , (IV isomer 2).

Excellent molar yields of the butadiene used can be achieved for the addition product of formula IV, which by definition X may be a ketoester or diester, this yield may be 90% or better if the addition reaction is followed by Is carried out under preferred conditions from 1 to 8:

Use of a compound of formula (III) containing from 1 to 1.5 moles of active methylene group per mole of optionally substituted butadiene (II);

Using 2 (III) reagent comprising an active methylene group wherein X is R ^6;

3. soluble phosphine is used, which may be (sulfophenyl) diphenylphosphine, di (sulfophenyl) phenylphosphine and tri (sulfophenyl) phosphine sodium, potassium, calcium, barium, ammonium, tetramethylammonium - and tetraethylammonium salt;

···· ····

4. as a rhodium compound, one of the following water-soluble compounds may be used: rhodium oxide, Rh ₂ O ₃ , rhodium chloride RhCl ₃ , rhodium bromide RhBr ₃ ; rhodium sulfate Rh ₂ (SO ₄ ) ₃ ; rhodium nitrate Rh (NO ₃ ) ₃ ; rhodium acetate [Rh (CH ₃ CO ₂ ) ₃ ]; tetracarbonyl-rhodium [Rh (CO) ₄ ] ₂ ; trivalent rhodium acetylacetonate; (1,5-cyclooctadiene) rhodium chloride [Rh (C ₈ H ₁₂ ) Cl] ₂ ; or dicarbonyl-rhodium chloride [Rh (CO) ₂ Cl] ₂ ;

5. the amount of rhodium used, expressed as grams of rhodium, is 1/100 mol butadiene, between 0,02 and 20;

6. the amount of phosphine is from 1 to 10 moles of compound per mole of rhodium;

7. an alkali metal such as sodium or sodium hydroxide, carbonate or bicarbonate; this is added to the reaction mixture for the purpose of improving reactivity and is present in an amount of 0.01 to 3 moles base / liter water and is part of the reaction medium;

8. the reaction temperature is between 50 ° C and 150 ° C and maintained for a time depending on the temperature chosen, for example from 2 hours if the reaction is carried out at 100 ° C to 5 hours if the reaction is 80 ° C. ° C.

For further details of the addition reaction of step (a), reference is made to European Patent Application No. 00 44 771.

Regarding step (b) of step (b) of the process of the invention, the deacylation reaction of the ketoester of formula (IV) consists in replacing the removable COX group, where X is R ⁶ , with a hydrogen atom to give the ester of formula (V) and then the ester of formula (V) is subjected to alkaline hydrolysis followed by acidification of the reaction to give the desired in situ salt of the carboxylic acid of formula (VI).

In variant (b'i) of step (b) of the present invention, the two esters of COOR ⁵ and COOR ^{6 are} subjected to alkaline hydrolysis from the diester of formula IV to give a compound containing two alkaline carboxylate groups as intermediate, followed by two basic carboxylate groups one is decarboxylated after acidifying the medium and the resulting basic carboxylate group is converted to the COOH carboxyl group to give the desired carboxylic acid of formula VI.

These reactions can be carried out in known manner, for example in Bull. Chem. Soc. Japan, 52 (1), 216-217 (1979), which is incorporated herein by reference.

In view of the above (see, for example, step (a), reaction condition 2, step (b) is mainly carried out starting from the compound of formula (IV), which is in the form of a ketoester, i.e., variant (bii).

Excellent molar yields can be achieved for the carboxylic acid of formula (VI) relative to the ketoester of formula (IV) used, which may be up to 80% or more if carried out under the following conditions (1-7) the reaction, preferably a combination thereof, may be used:

•••••••••••••••••••••••••••••••

9 ··· · ♦

1. deacylating alkali metals, such as sodium and potassium, and linear and branched primary C 1 -C 5 monoalcohols, such as methanol and alkoxides derived from ethanol;

2. use of alcoholic alkoxide solutions in which they are prepared and containing up to 20 moles of alcohol, more particularly 5 to 15 moles of alcohol per mole of alkoxide base;

3. Use 1 to 1.5 moles of alkoxide base per mole of the starting ketoester of formula IV,

4. the deacylation reaction is generally conducted at a temperature corresponding to the boiling point of the alcohol used, as long as it is sufficient to remove in situ the compound of formula R ⁶ -CO-G, where G is the organic residue of the alkali metal alkoxide used, G is OCH ₃ when an alkali metal alkoxide such as CH ₃ ONa is used and the reaction time is for example 2 to 6 hours;

5) carrying out the alkaline hydrolysis reaction by adding 10 to 30 moles of water to 1 mole of an alkali metal alkoxide base after completion of the deacylation reaction, i.e. removal of the R ⁶ -CO-G compound;

6. carrying out the alkaline hydrolysis reaction at a temperature generally consistent with the reflux temperature of the reaction mixture and for a time sufficient to remove by distillation the alcohol present in the reaction mixture;

7. the hydrolysis reaction is carried out in such a way that the resulting aqueous reaction mixture is a strong inorganic mono- or polylic acid · ·······················································································

By adding 10 specific amounts, the pH is adjusted to 1-3, which may or may not contain oxygen, such as hydrochloric acid, nitric acid and sulfuric acid.

Deacylation and alkaline bridge lysis reaction are described in detail in Bull. Chem. Soc. Japan, 52 (1), 216-217 (1979).

In step (c) of the process of the invention, a carboxyl group is added to the carbon atom of the carboxylic acid having the substituent R ^{1 of} formula VI. In the synthesis, 1 mole of carbon monoxide and 1 mole of water are added to each mole of the carboxylic acid of formula (VI) to be converted.

According to variant (ct), a first method of synthesis consists of using formic acid and CO as a water and using a strong acid catalyst. A similar reaction is known in the literature (see New J. Chem., 1992, 16, 521-524), but this reaction has never been applied to a material corresponding to the structure of the monocarboxylic acid of formula (VI). dicarboxylic acid.

Another preferred synthesis method, corresponding to variant (c'i), is the direct reaction of carbon monoxide gas under pressure in the presence of a strong acid catalyst, and a similar reaction is known in the art, see in particular Russian Chemical Reviews, 58 , (2), 117-137 (1989), but was not used in the structure corresponding to the carboxylic acid of formula (VI).

- 11 • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

In the case of variant Α (ο ',), which is the most widely used method, excellent production of dicarboxylic acid of formula VII can be achieved with respect to monocarboxylic acid of formula VI. This yield may be up to 85% or more, provided that the following 1-7 advantageous conditions are achieved, preferably a combination thereof:

1. The reaction is carried out in a suitable reactor with a large excess of carbon monoxide, i.e. more than 2 moles of carbon monoxide are used per mole of the starting compound (VI) which is hydroxycarbonylated and the carbon monoxide gas is pressurized at the desired pressure. Charged from MPa to 10 MPa;

2. ensuring that all required components in the reactor are present in the reactor from the start of the reaction;

3. the catalyst used is a strong inorganic or organic mono- or poly-acid, which may or may not contain oxygen, at least one acid functional group of which, if more than one is present, has an ionization constant in water, i.e. less than 3 pKa or and are, for example, inorganic acids, hydrochloric acid, sulfuric acid, orthophosphoric acid or pyrophosphoric acid, organic acids, organosulfonic acids, especially para-toluenesulfonic acid, methanesulfonic acid or naphthalenesulfonic acid, organophosphonic acids, in particular mono-alkyl or mono-aryl phosphonic acids, such as methylphosphonic acid or phenylphosphonic acid, or strong polyhalogenated carboxylic acids, such as dihalogen and trihalogen, especially chlorine and fluorine. · · · · · · · ······· · ·

- 12-Acetic or propionic acids. Sulfuric acid is particularly suitable as a strong acid;

4. the hydroxycarbonylation reaction is carried out using 1-15 moles of water and 10 to 50 H ⁺ ions for each mole of the starting carboxylic acid of formula VI;

5. introducing the reaction water and the strong acid together in the form of an aqueous strong acid solution concentrated in the reaction medium, wherein the mass concentration and amount of the pure acid are determined by entering the amount of water and the H ⁺ ion number required.

6. using concentrated aqueous strong acid solution wherein the concentration of pure acid is 90-98% by weight;

7. Reaction temperature from 20 ° C, i.e. room temperature

It can vary up to 100 ° C and is maintained until the CO absorption ceases.

In another variant of (cO), the reaction is carried out under the following preferred conditions 1-6, and combinations thereof are preferably used:

1. the reaction is carried out by introducing formic acid (variant c _n ) or a mixture of formic acid and the starting carboxylic acid of formula VI (variant C1, ₂ ) into the reactor, which in the case of variant (Cu) is a strong acid catalyst and It contains the carboxylic acid of formula (VI) or, in the case of variant ( _c12 ), contains only a strong acid catalyst;

2. the amount of formic acid used is from 1 to 4 moles, based on the molar amount of the compound, per mole of the carboxylic acid of formula VI;

··· · ····

Catalyst 3 is a compound as defined above, see Criterion 3, wherein variant (c'i) is used;

4. the strong acid catalyst is used in pure form or in the form of a concentrated aqueous solution, wherein the concentration of the pure acid is at least 95% by weight;

5. The amount of strong acid catalyst is expressed as the number of hydrogen ions per mole of the starting carboxylic acid of formula VI: 5 to 40 H ⁺ ;

6. The reaction temperature is from room temperature (20 ° C) to 100 ° C and is maintained for 3 to 6 hours depending on the temperature.

The hydroxycarbonylation reaction is described in detail based on the chemical reference books and the aforementioned Russian Chemical Reviews, 58 (2), 117-137 (1989) and New J. Chem., 1992, 16, 521-524. as described in the literature.

In step (d) of the process of the invention, the dicarboxylic acid (VII) is cyclized to give the cyclopentanone (I).

According to a first method of synthesis, i.e., (d6), the diacid is converted to a cyclic anhydride by reacting a lower carboxylic anhydride which loses carbon dioxide during the reaction, and a similar reaction can be carried out in a known manner. , in particular Compt. Order 142. 1084-1085 (1906) and Compt. Order 144, 1356-1358 (1907).

In another synthesis method corresponding to (d'i), the diacid is pyrolyzed in either a liquid or a gas phase.

- 14 Ban in the presence of a special catalyst, a similar reaction is known in the literature, see in particular Bull. acad. Sci. URSS, classe sci. chim., (29-40), 489-493 (1947) and J. Org. Chem., 25, 1841-1844 (1960), but the catalyst used in the present invention is not described therein.

In variant (d'i), excellent molar yields of the desired cyclopentanone of formula (I) with respect to the dicarboxylic acid of formula (VII) can be achieved, up to 75% or more, and the pyrolysis reaction in the following 1 -6. may be performed under advantageous conditions, preferably using a combination thereof:

1. The cyclization decarboxylation reaction is carried out in a liquid phase, i.e. in the presence of a solvent, which may be an organic solvent or a mixture of organic solvents which are inert to the starting dicarboxylic acid and the resulting cyclic ketone and have a high boiling point they boil at a temperature. Particularly preferred organic solvents are paraffinic hydrocarbons such as decane, undecane, dodecane or tetradecane; aromatic hydrocarbons such as xylenes, cumene or petroleum, distillates consisting of a mixture of alkylbenzenes, in particular Solvesso-type distillates; heavy esters of inorganic acids, such as tricresol 1-phosphate or esters of carboxylic acids, such as octylphthalate, aromatic ethers, such as diphenyl ether or dibenzyl ether; residues from oil distillation, paraffinic and / or naphthenic oils;

2. the concentration of the starting dicarboxylic acid of formula (VII) in the reaction mass, which is the reaction mass of the starting material.

It consists of 15 diacids, a catalyst and an organic solvent or solvents, generally 10 to 50% by weight of the reaction;

As catalyst 3:

(i) rubidium, cesium, vanadium, molybdenum, boron, aluminum, gallium, indium, thallium, tin, antimony or bismuth, in the form of: metal or metalloid; single or double oxide or simple or double hydroxide; or a simple or double inorganic salt such as nitrate, sulfate, oxysulfate, halide, oxyhalide, silicate or carbonate; or a simple or double organic salt such as acetylacetonate or alkoxide such as methoxide or ethoxide or a carboxylate such as acetate or oxalate. Examples of type (i) catalyst include: sodium or potassium tetraborate, tin oxide, sodium or potassium stannate, bismuth, cesium or rubidium carbonate; molybdenum, aluminum, indium or antimony oxide; or thallium acetate;

Types (2i): Phosphate or condensed phosphate, pyrophosphate or polyphosphate catalysts in which the cation may be derived from Group 1A (except rubidium and cesium), Group 2A or Group 3B in the periodic table, see Bulletin of the Société Chimique de France, 1. (1966), or it may be an ammonium cation. Particular mention may be made of catalysts of the type (2i): sodium or potassium phosphates, pyrophosphates, tripolyphosphates or penta polyphosphates;

···· ····

4. The amount of catalyst is expressed in grams of the metal cation per 100 moles of dicarboxylic acid, which may be from 0.1 to 30%, more particularly from 5 to 20%;

5. carrying out the cyclization-decarboxylation reaction at 200-300 ° C, which corresponds to the reflux temperature of the reaction mixture;

6. carrying out the cyclization-decarboxylation reaction by distillation to remove the cyclic ketone, carbon dioxide gas and water; at the end of the reaction, the cyclic ketone is recovered from the distillate in a known manner, in particular by sedimentation or crystallization.

Further details of the invention are illustrated by the following examples.

Example 1

The following example illustrates the process (a) according to the invention.

The following components were introduced into a stainless steel autoclave pre-purged with nitrogen in sequence;

- 93.6 mg of [Rh (1,5-cyclooctadiene) Cl] ₂ -t, i.e. 3.8Ί0 ^'4 gram atoms of elemental rhodium,

- 1.208 g (11.4Ί0 ^'3 mole) of sodium carbonate,

- 2.736 g of 30 wt% (a) the formula tri (sulfophenyl) phosphine, sodium salt aqueous solution, i.e. 14.4Ί0 ^'4 moles of phosphine,

- 80 ml of de-gasified distilled water, bubbled with nitrogen,

34 g, 0,50 mol of freshly distilled isoprene, and

71.8 g (0.62 mol) of methyl acetoacetate.

- 17 ···· ·· ·· ·· • · · · · · · · · · · · · · • • · · · · · ······

After closing the autoclave, 2 x 10 ⁵ Pascal pressurizing nitrogen, and heated at 100 ° C for 2 hours under autogenous pressure.

After cooling, decant the contents of the autoclave into a separatory funnel where the aqueous and organic phases are separated. The collected aqueous phase contains the catalyst and the catalyst-free upper organic phase contains the desired addition product of formula IV.

The separated organic layer was washed with 20 mL of brine. The aqueous phase was extracted with ethyl acetate (50 mL) and washed with brine (20 mL). The organic layers were combined and dried over anhydrous sodium sulfate. After filtration of the sodium sulfate, the ethyl acetate was removed by evaporation under reduced pressure and the resulting crude product was purified by distillation under reduced pressure (70-72 ° C, 3 10 ² Pascal).

91.14 g of a colorless liquid are obtained which, by NMR, mass spectroscopy, IR spectroscopy and gas-phase chromatography, contains 99% by weight of the ketoester b, which corresponds to 98% molar yield of the isoprene used.

Example 2

This example illustrates process (b) according to the invention.

600 ml of anhydrous methanol was introduced into a 1-liter, three-necked round-bottomed flask, pre-purged with argon and mechanically agitated, a thermometer, a 250 ml dropping funnel and a distillation column.

Sodium (27.6 g, 1.20 mol) cut into fine strips was then gradually introduced into the round bottom flask. When all the sodium

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179.2 g (0.974 mol) of the keto ester prepared in Example 1 are introduced over 10 minutes and the resulting solution is refluxed. The methyl acetate formed in situ is distilled as it is formed, as is the methanol present in the reaction medium. This distillation operation requires heating for 3 hours.

Subsequently, 400 ml of distilled water were added continuously during the distillation operation, taking care to remove the methanol remaining in the reaction medium.

When all methanol was removed, the resulting reaction mixture was cooled and washed with 100 mL of cyclohexane. The separated aqueous phase is then acidified to pH 2 with sulfuric acid.

The expected carboxylic acid of formula (VI) is spontaneously released by sedimentation. The aqueous phase was immediately extracted twice with 100 ml of dichloromethane each time. The organic layers were combined and dried over anhydrous sodium sulfate. After filtration of the sodium sulfate, the dichloromethane is evaporated under reduced pressure and the crude product obtained is purified by distillation under reduced pressure. At 70-74 ° C and at a pressure of ^{3 to 2} Pa. 108.3 g of a colorless liquid are obtained which, by NMR, IR and gas chromatography, contains 95% by weight of the carboxylic acid of formula C, which corresponds to a molar yield of 82.5% with respect to the ketoester used.

Example 3

This example illustrates process (c) according to the invention.

··· · ·

«

- 19,358.7 g of concentrated aqueous sulfuric acid solution containing 95% by weight of pure acid, i.e. 6.95 H ⁺ and 0.997 moles of water, was filled with a 250 ml three-necked stopper fitted with a mechanical stirrer, a thermometer and a 50 ml drip funnel. flask.

The carboxylic acid (32 g, 0.25 mol) prepared in Example 2 is then added slowly with stirring while maintaining the temperature at 5 ° C. The solution thus obtained is then decanted into an autoclave containing an inner tantalum lining and this autoclave is stirred at 20 ° C and 5 mPa CO.

After 1 hour of contact with carbon monoxide, the reaction mixture is slowly poured into 500 ml of water, kept at 10 ° C. A solid precipitates which is isolated by filtration and washed with 50 ml of cold water. After drying, 39.2 g of a white solid are obtained, which is determined by NMR, IR and HPLC chromatography.

It contains 92.5% by weight of dicarboxylic acid of formula (d).

The resulting filtrate was diluted with 1 liter of water and kept at 4 ° C for 12 hours. This allows an additional 3.17 g of the desired dicarboxylic acid to be isolated in pure form.

The total molar yield of dicarboxylic acid relative to the monocarboxylic acid used is 90.8%.

Example 4

This example illustrates process (d) according to the invention.

18.6 g of diphenyl ether solvent, 5 g of 28.7-0.3 mol of 2,2-dimethyladipic acid prepared in Example ³ and 1.056 g of Na ₂ B ₄ O ₇ -10 H ₂ O, i.e. 5, 6-10 ' ³ grams of sodium-

- 20 · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · in a 50 ml three-necked round-bottomed flask fitted with a distillation column and a cooled carbon dioxide stopper.

The reaction mixture is heated with stirring for 15 minutes until the reflux temperature of the solvent used, i.e. 250 ° C, is reached. The temperature is then maintained at 250 ° C, and the resulting cyclic ketone is distilled off until it is exhausted in a solid carbon cooled capture vessel for 1 hour 35 minutes.

The resulting distillate containing 6.357 g of the resulting cyclic ketone, water and diphenyl ether was obtained. The water is absorbed onto anhydrous disodium sulfate. After filtration, after rinsing with dichloromethane, the distillate is made up to 100 ml with dichloromethane and the dimethylcyclopentanone in this solution is analyzed by gas-phase chromatography using an internal standard.

Dichloromethane (20 ml) was added to the distillation residue and the extraction was carried out twice with 20 ml of a 60:40 mixture of water and sodium hydroxide, and the unconverted dimethyl adipic acid in the aqueous phase was subjected to HPLC chromatography.

The results obtained are as follows:

- with GPC, the molar dimethylcyclopentanone yield is 80% relative to the dicarboxylic acid used,

- the molar conversion rate of the dicarboxylic acid used is 87%,

- molar dimethylcyclopentanone yield 92% relative to the converted dicarboxylic acid.

Claims (26)

A process for the preparation of a cyclopentanone, mono- or disubstituted at the 2-position of formula (I), wherein R ¹ is hydrogen, straight or branched C 1 -C 4 alkyl or alkoxy, or (R ² ) p -phenyl - (- CR ³ R ⁴ -) q, wherein R ² is a straight or branched C 1 -C 3 alkyl group, R ³ and R ⁴ may be the same or different and are hydrogen or straight or branched C 1 -C 3 alkyl, and p and q may be the same or different from 0 to 3, characterized in that performing the following four steps (a) to (d) sequentially in the same reactor as needed: - Step (a) consisting of: * (X) is a formula, optionally in the formula (II) substituted at 2-position of 1,3-butadiene which is reacted with R ¹ is as defined for formula (I) containing compound (III) active methylene group wherein X R ⁶ or OR ⁶ and R ⁵ and R ^{6 are the} same or different and are linear or branched C 1 -C 6 alkyl groups and this reaction is carried out in an aqueous medium in the presence of a catalyst consisting of at least one water-soluble phosphine at least one rhodium compound- of compound of formula (IV) 22 * * · ····························• wherein R ¹ , R ⁵ and X is (I) and (III) wherein the general formulas, * and formula ₍₂₎ to (IV) of product which is in the organic phase is isolated in such a way that the latter is selected by settling an aqueous phase containing the catalyst, optionally purifying the product by extraction with a suitable solvent and / or distillation; - (b) within the organic phase from ₍₂₎ step (IV) of the formula above for the crude product or the pure product * (bj) a compound of formula (IV) wherein X is R ^6, the compound (b _ri) deacylated by known methods to the alcohol with the alkali metal alkoxidos solution, where it is prepared, (V), the product of formula of the formula wherein ^R1 and ^R5 are as defined in formula (IV), (bi ₂₎ and the -COOR ^5-ester group to alkaline hydrolysis and acidifying, in a known manner, in the same reaction medium to provide the product of formula (VI), wherein R ¹ is as defined for the compound of formula (I); * (B'i) where (IV) compound of the formula is used, its wherein X is OR ^6, then this compound (b'1.1) subjecting the ester groups -COOR ⁵ and -COOR ⁶ alkaline hydrolysis, (b _'12) followed by the subsequent decarboxylation of one of the carboxylate groups formed and acidification, in known manner, in the same reaction medium to afford the product of formula (VI), wherein R ¹ is as defined for the compound of formula (I); (b ₂ ) isolating the monocarboxylic acid product (VI) in the aqueous phase, separating it from the organic phase present, optionally extracting the product with a suitable solvent; - (c) the acid of formula (VI) is used as a crude product or as a pure product in the aqueous phase obtained from step (b ₂ ), and (c) the compound is hydroxycarbonylated directly with carbon monoxide gas at 1 MPa to 10 g; MPa at CO pressure using water and a strong inorganic or organic acid catalyst to produce the product of formula VII wherein R ¹ is as defined in formula I and then * (c ₂ ) the dicarboxylic acid product of formula VII is isolated by: to precipitate the compound by adding water to the reaction medium and optionally purifying the diacid by recrystallization; - (d) the dicarboxylic acid of formula (VII) which is used as a crude or pure product by precipitation after step (c ₂ ) and is subjected to a cyclization-decarboxylation reaction, which is carried out in a first step. by converting the diacid into a cyclic anhydride by reaction with a lower carboxylic acid anhydride which ···· - loses 24 ϊ of carbon dioxide to give the desired cyclopentanone of formula (I); * (d'i) subjecting this compound to a cyclization-decarboxylation reaction which is carried out in the second variant by pyrolysis of the diacid in a liquid or gaseous phase in the presence of a catalyst: (i) Rb, Cs, V, Mo, B, Al, Ga, In, TI, Sn, Sb or Bi in the form of metal or metalloid or a derivative thereof, or (2i) a phosphoric acid derivative wherein the acid may be condensed or non-condensed, and whose protons may be substituted with a metal cation other than the metal or metalloid listed in (i) or with an ammonium cation to produce the desired cyclopentanone of formula (I) and * (d ₂ ) the product is suitably isolated. Process according to claim 1, characterized in that four steps (a) to (d) are carried out in succession, which can be carried out sequentially in the same reactor if desired: - Step (a) consisting of: * (a) reacting a 2-substituted 1,3-butadiene, wherein R ¹ is the above compound of formula (III) containing an active methylene group, wherein X is R ⁶ , R ⁵ and R ⁶ may be the same or different and each may represent a straight or branched C 1 -C 6 alkyl group and the reaction is carried out in aqueous medium in the presence of a catalyst which may be at least one water-soluble phosphine, and ···· - 25 liters of at least one rhodium compound for the preparation of a compound of formula IV wherein R ¹ , R ⁵ and X are as defined above, and then (a ₂ ) a compound of formula IV isolated from the organic phase by the latter is separated from the aqueous phase containing the catalyst by settling and optionally the product is extracted with a solvent and / or purified by distillation; - (b) reacting the compound of formula (IV) is used in the form or pure form crude organic phase obtained ₍₂ step a), and * (bD this compound (boo) deacylating a known manner, using a solution in alcohol, alkali metal alkoxide solution of for the preparation of the product of formula (V) wherein R ¹ and R ⁵ are as defined for compound (IV), (b ₁₂ ) the reaction is carried out by alkali hydrolysis of the ester group of COOR ⁵ and then acidified and known in the art. is carried out in the same reaction medium to produce the product of formula (VI), wherein R ¹ is as defined for the compound of formula (I); then * (b ₂ ) isolating the monocarboxylic acid of formula (VI) in the aqueous phase, separating in this case the product is purified by solvent extraction; - (c) using the acid of formula (VI) as a crude product or in pure form from the aqueous phase obtained in step (b ₂ ), and - 26 • · · · ··· · · · ··· I * (c'i) this compound is hydroxycarbonylated directly using CO gas at 1 MPa to 10 MPa and water and a strong inorganic or organic acid catalyst are used to prepare the compound of formula VII, wherein R ¹ is as defined above, followed by * (c ₂ ) isolating the dicarboxylic acid of formula (VII) by precipitating the reaction medium with water and optionally purifying the diacid by recrystallization; - (d) the dicarboxylic acid of formula (VII) which is used as a crude product or a pure product by precipitation of the product of step (c ₂ ) and * (d'i) by decarboxylation of this compound by cyclization of the diacid in liquid or gas phase in the presence of a catalyst , which can be: (i) an elemental metal or metalloid of Rb, Cs, V, Mo, B, Al, Ga, In, TI, Sn, Sb or Bi or a derivative thereof, or (2i) a phosphoric acid derivative, wherein the acid may or may not be condensed, and which may be substituted protons of different metals listed in (i) metalloidtól metal cation or ammonium cation, the desired (s) of the desired cyclopentanone represented by formula, and * (d ₂₎ in accordance with the product isolated. The process according to claim 1 or 2, wherein R ¹ is methyl, while R ⁵ and R ⁶ may be the same or different and may be methyl or ethyl. • · · · · · · · · · - - 27 - Process according to claim 2 or 3, characterized in that in step (a) a compound of formula (III) containing from 1 to 1.5 moles of active methylene is added to 1 mole of optionally substituted butadiene (II). 5. Process according to any one of claims 1 to 3, characterized in that the soluble phosphine used in step (a) is selected from the group consisting of (sulfophenyl) diphenylphosphine, di (sulfophenyl) phenylphosphine and tri (sulfophenyl) phosphine sodium. potassium, calcium, barium, ammonium, tetramethylammonium or tetraethylammonium salts. 6. The process according to any one of claims 1 to 3, wherein in step (a) one of the following water-soluble compounds is used as rhodium compound: rhodium chloride RhCl ₃ ; rhodium bromide RhBr ₃ ; rhodium sulfate Rh ₂ (SO ₄ ) ₃ ; rhodium nitrate Rh (NO ₃ ) ₃ ; rhodium acetate Rh (CH ₃ CO ₂ ) ₃ ; tetracarbonyl rhodium [Rh (CO) ₄ ] ₂ ; 3-rhodium acetylacetonate; (1,5-cyclooctadiene) rhodium chloride [Rh (C ₈ H 1 ₂₎ Cl] _2; or dicarbonyl-rhodium chloride [Rh (CO) ₂ Cl] ₂ . 7. The process according to any one of claims 1 to 3, wherein the amount of rhodium in step (a) is selected from 0.02 to 20, expressed as grams of elemental rhodium, per 100 moles of butadiene. 8. The process according to any one of claims 1 to 3, wherein in step (a) the phosphine is used in an amount of 1 to 10 per molar amount of elemental rhodium. ·· · · - - 28 - 9. Process according to any one of claims 1 to 3, characterized in that the reaction temperature in step (a) is between 50 and 150 ° C. 10. Process according to any one of claims 1 to 3, characterized in that the acylation reaction in step (b) involves alkoxides derived from alkali metals and from 1 to 5 straight or branched primary monoalcohols. 11. Process according to any one of claims 1 to 3, characterized in that the deacylation in step (b) uses from 1 to 1.5 moles of alkoxide base per ketoester of formula IV. 12. A 2-11. A process according to any one of claims 1 to 5, wherein the deacylation reaction in step (b) is carried out at a temperature corresponding to the boiling point of the alcohol used and the reaction time is sufficient to remove R ⁶ -CO-G formed in situ, wherein G is the organic residue of the alkali metal alkoxide used. 13. A 2-12. The process according to any one of claims 1 to 3, wherein in step (b) the alkaline hydrolysis is carried out by adding to the reaction medium 10 to 30 moles of water per mole of alkali metal alkoxide base after completion of the deacylation reaction. 14. 2.-13. A process according to any one of claims 1 to 3, wherein in step (b) the alkaline bridge lysis is carried out at a temperature corresponding to the reflux temperature of the reaction mixture. ···· ···· - - 29 -! 15. A 2-14. A process according to any one of claims 1 to 3, wherein the catalyst in step (c) is a strong inorganic or organic mono- or polyacid, optionally containing oxygen, and having at least one acidic functional group in water having a pKa ionization constant of less than 3 or equal to that. 16. Process according to any one of claims 1 to 3, characterized in that in step (c) the hydroxycarbonylation reaction is carried out using 1-15 moles of water and 10-50 H ⁺ ions per mole of the starting carboxylic acid of formula (VI). 17. A 2-16. A process according to any one of claims 1 to 3, wherein in step (c) the water and the strong acid required for the hydroxycarbonylation reaction are simultaneously introduced into the reaction medium in the form of an aqueous strong acid solution concentrated in a concentration and amount of pure acid and introducing H ⁺ into the mixture. 18. The process of claim 17, wherein the concentrated aqueous strong acid solution is present in a concentration of 90 to 98% by weight of pure acid. 19. A process according to any one of claims 1 to 3, wherein the temperature of the hydroxycarbonylation reaction in step (c) is from room temperature (20 ° C) to 100 ° C. 20. A process according to any one of claims 1 to 3, wherein the cyclization-decarboxylation reaction in step (d) is carried out in a liquid phase, i.e. an organic solvent or 30 liters of organic solvents which are inert to the starting dicarboxylic acid and also to the resulting cyclic ketone, each having a high boiling point between 200 and 500 ° C. A process according to claim 20, wherein the solvent is paraffinic hydrocarbon, preferably dean, undecane, dodecane or tetradecane; an aromatic hydrocarbon, preferably xylene, cumene or petroleum distillate, which is a mixture of alkylbenzenes; ether, paraffin and / or naphthalene oils or oil distillation residues. 22. A 2-21. Process according to any one of claims 1 to 3, characterized in that in step (d) the concentration of the starting dicarboxylic acid of formula (VII) in the reaction mixture formed from the starting diacid, the catalyst and the organic solvent is 10-50% by weight. 23. The process according to any one of claims 1 to 3, wherein the catalyst used in step (d) is: (i) rubidium, cesium, vanadium, molybdenum, leather, aluminum, gallium, indium, thallium, tin, antimony or bismuth, which may be derived from metal or metalloid; single or double oxide, single or double hydroxide; or a simple or double inorganic salt such as nitrate, sulfate, oxysulfate, halide, oxyhalide, silicate or - 31% carbonate; or a simple or double organic salt such as acetylacetonate, alkoxide, or carboxylate; (2i) The catalyst may also be of the phosphate or condensed phosphate, pyrophosphate or polyphosphate type having a structure consisting of a member from Group 1A of the Periodic Table, except rubidium and cesium, or a member of Group 2A or 3B of the Periodic Table. the Bulletin de la Societe Chimique de France, No. 1 (1966), or ammonium cation. 24. In Figs. The process according to any one of claims 1 to 3, wherein the amount of catalyst in step (d) is 0.1 to 30% per 100 moles of dicarboxylic acid, expressed as grams of metal cation. 25. A 2-24. A process according to any one of claims 1 to 3, characterized in that - in step (d), the cyclization decarboxylation is carried out at 200-300 ° C, at a temperature corresponding to the reflux temperature of the reaction mixture; - distillation to remove the cyclic ketone, carbon dioxide gas and water formed during formation. 26. A process for the preparation of a dicarboxylic acid of formula VII, wherein R ¹ is as defined above, characterized in that a monocarboxylic acid of formula VI, wherein R ¹ is as defined above, directly with carbon monoxide gas at a pressure of 1 MPa to 10 MPa CO. and hydroxycarbonylation using a strong inorganic or organic acid catalyst to precipitate the product of Formula VII by adding water and optionally purifying the diacid by recrystallization.