FR2643635A1 - PROCESS FOR THE PREPARATION OF (ALPHA) -ALKYL-LACTONES - Google Patents

Abstract

The present invention relates to a process for the preparation of alpha-alkyl-lactones. The process according to the invention comprises 1 reacting substantially equimolar amounts of an alpha-acyl-lactone, of an aldehyde of the formula R'CHO in which R 'is hydrogen or a hydrocarbon radical having from 1 to 20 atoms. of carbon, and an alkali metal hydroxide, at a temperature in the range of 50 degree (s) C to 150 degree (s) C in an inert solvent with removal of the water of reaction and hydrogenation of the product obtained in step 1 under conditions which do not reduce the carbonyl group and which do not cause ring opening. The process is intended for the preparation of alpha-alkyl-gamma-butyrolactones and alpha-alkyl-delta-valerolactones.

Description

The present invention relates to the preparation of α-ALKYL-LACTONES.

  an improved process for preparing α-alkyl lactones. This process comprises reacting an? -Acyl lactone, an aldehyde and an alkali metal hydroxide in a suitable solvent to form the alkylidene lactone and then the hydrogenation for

  obtain the corresponding α-alkyl-substituted product.

  Considerable interest has been placed in the preparation of α-alkylidene lactones and their saturated analogs, i.e., α-alkyl lactones. Different γ-butyrolactones bearing α-alkyl substituents have been described as having flower or

fruit.

  Routes of synthesis of α-alkylidene products

  substituted compounds generally comprise either (a) forming α-methylene or α-alkylidene lactone from acyclic precursors containing all desired functional groups via a ring closure reaction, ie b) converting an existing group at position a on a preformed lactone ring into the corresponding α-methylene or α-alkylidene group. The α-alkylidene derivative can then be conveniently hydrogenated to the corresponding α-alkyl-lactone. The present invention relates to a process in which the hydrogen and acetyl substituents present at the α-position of a lactone ring are first removed and replaced by an α-alkylidene group and the alkylidene group is then hydrogenated (reduced) to obtain a -alkyl-ybutyrolactone or a

a-alkyl-valerolactone.

  Many methods of synthesizing α-methylene

  lactones are discussed in the papers by P. A. Greico (Synthesis 1975, 67) and N. Petragnani et al (Synthesis 1986, 157). However, none of the reactions described in these references relate to the preparation of α-alkylidene lactones. In fact we only find a mention of the reaction of an acetyl group which is located in position a. Ueno and others (Tetrahedron Lett., 1978, 3753) describe the reaction of α-acetyl butyrolactone with paraformaldehyde, lithium diisopropylamide in the

  tetrahydrofuran to produce α-methylene-y-

  butyrolactone. Ksander et al (J. Org Chem 1977, 42, 180) describe the preparation of α-alkylidene lactones by the reaction of ethyl oxalyl butyrolactones with an aldehyde in the presence of aqueous sodium hydroxide. Ksander et al. Do not suggest the use for lactones reaction

  α-acyl-substituted ones of any type.

  Ono et al (J. Org Chem 1983, 48, 3678) describe the conversion of an ester group which is located at the α-position of an γ-butyrolactone ring to an α-isopropylidene group. The complex multi-step process involves the reaction of the

  carbanion of a-carboethoxy-γ-butyrolactone and chlorobenzene

  2-nitro-2-propane in the presence of a Watts tungsten lamp then the addition of sodium bromide and the application of heat. In the only situation where Ono and others use a cyclic structure carrying an acetyl group in the α position, namely acetyl-2-cyclopentanone, the corresponding α-isopropylidenecyclopentanone is not produced. Murray et al. In J. Chem. Soc., Chem. Commun., 1986, pp. 132-133 describe a multi-step synthesis which comprises the formylation of γ-lactone with sodium hydride and ethyl formate followed by the condensation of the obtained enolate with a aldehyde for

  to obtain the corresponding α-methylene-γ-lactone.

  Various techniques are known for hydrogenating unsaturated hydrocarbon substituents on a lactone or other ring systems. It would be very interesting to have a method for easily replacing the acyl substituent on a lactone with an alkylidene group which, in turn, could be hydrogenated to produce the corresponding alkyl-substituted lactone. The method according to the present invention, which will be described in more detail below, makes it possible to obtain these advantages.

as well as other benefits.

  The present invention relates to an improved process

  for the preparation of α-alkyl-γ-butyrolactones and α-alkyl-b-

  valerolactones. In general, the process comprises reacting essentially equimolar amounts of an α-acyl lactone, an aldehyde and an alkali metal hydroxide in an inert solvent at a temperature in the range of 50 ° C. at 150 ° C. while withdrawing the water of reaction to form the corresponding α-alkylidene-lactone and then the hydrogenation to obtain the α-alkyl-lactone. Preferably, the solvent used in the reaction to produce the α-alkylidene derivative forms an azeotrope with boiling water in the range of 50 ° C to 95 ° C. Typically, the solvent is used at a volume ratio ( solvent: total charge of reactants) from 1: 1 to: 1. In a particularly useful embodiment of the invention, the α-acyl lactone and the alkali metal hydroxide are combined and reacted prior to addition of the aldehyde. When this method is used, the aldehyde is generally added when about 60% to 75% of the theoretical amount of water has been removed from the reaction mixture. The α-acyl lactones used in the process may contain one or more hydrocarbon radicals which have from 1 to 20 carbon atoms on the ring. The hydrocarbon radicals may be substituted alkyl, cycloalkyl, aryl or aryl groups. If several hydrocarbon substituents are present, the total number of carbon atoms of the substituents combined should not typically exceed about 20. The acetyl group is the preferred acyl group. The aldehydes correspond to the formula R'CHO in which R 'is a hydrogen or a hydrocarbon radical which has from 1 to 20 carbon atoms and the alkali metal hydroxide may be sodium hydroxide, which is preferred, potassium hydroxide or lithium hydroxide. Benzene, toluene, xylene and cyclohexane are particularly useful solvents for carrying out the reaction. Conventional hydrogenation techniques are used to hydrogenate the alkylidene group to the corresponding alkyl group. The hydrogenation catalyst and the hydrogenation conditions are chosen such that the carbonyl group is not reduced and there is no ring opening. In general, the hydrogenation is carried out under 1 to 30 bar of hydrogen and at a temperature between 0 C and 120 C. An inert solvent can be used for the hydrogenation. Supported heterogeneous catalysts based on platinum, palladium, nickel and ruthenium are preferred; however, homogeneous catalysts can also be used. Palladium and platinum on carbon, calcium carbonate or barium sulfate are particularly interesting. The amount of metal on the support is generally between 1 and 15% by weight and these catalysts are generally used for

  0.025 to 10% by weight relative to the α-alkylidene

  lactone. The present invention relates to a method for converting

  α-acyl-substituted lactones to α-alkyl-substituted lactones.

  Α-Alkyl substituents include methyl, n-alkyl and branched-chain alkyl groups, or alkyl groups which have cycloalkyl or aryl substituents, and the like. The butyrolactone derivatives according to the invention can also be denominated furanones. For example, the? -Acetyl-,? -Alkylidene- and? -Alkyl-substituted-3-acetylated? -Butyrolactones, respectively,

  3-acetyldihydro-2 (3H) -furanone, 3-alkylidene dihydro-

  2 (3H) -furanone and 3-alkyldihydro-2 (3H) -furanone. This nomenclature is particularly useful for designating compounds that have multiple substituents on the ring and

it is used here.

  The reaction to obtain the α-alkylidene lactone involves an acyl lactone, an aldehyde and an alkali metal hydroxide. Typically the reaction proceeds in an inert solvent. The method can be adapted for use in the case of any five- or six-membered lactone which has an acyl substituent at the α-position on the ring. The other positions of the ring may be substituted or not by one or more hydrocarbon groups. The α-acyl lactones which can be used in the process correspond to the general formulas: R 'RRX> </ 0 or H R1 III) (Ii) in which R * is a C1-C8 alkyl group and R1, R2, R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen and a hydrocarbon radical having 1 to 20 carbon atoms. The hydrocarbon radicals may be substituted alkyl, cycloalkyl, aryl or aryl groups. In general, when more than one hydrocarbon group is present on the lactone ring, the total number of carbon atoms of the hydrocarbon substituents combined does not exceed twenty. Particularly useful hydrocarbon radicals include C1-8alkyl, C3-6cycloalkyl, phenyl, C1-C8alkyl substituted phenyl, benzyl and C1-C8alkyl substituted benzyl. In a particularly useful embodiment of the invention, the lactone corresponds to formula I, R * is a C1-C4 alkyl group and R1, R2, R3 and R4 are hydrogen atoms or C1-C8 alkyl groups . In a further preferred embodiment, R * is a methyl group, R1 is a C1-8 alkyl group and R2, R3 and

R4 are hydrogen atoms.

  In another particularly useful embodiment, the lactone corresponds to Formula II, R * is C1-4alkyl and R1, R2, R3, R4, R5 and R6 are hydrogen atoms or C1-6alkyl groups. In a further preferred embodiment, R * is methyl, R1 is C1-8alkyl and R2, R3, R4, R5

and R6 are hydrogen atoms.

  The aldehydes used in the process have the general formula R'CHO wherein R 'is a hydrogen atom or a hydrocarbon group which has about 1 to 20 carbon atoms. The hydrocarbon group may be an alkyl, cycloalkyl, aryl or substituted aryl group as defined above for the lactone. When formaldehyde is chosen as the aldehyde, it is advantageous to use dioxane or paraformaldehyde in the process as a source.

of formaldehyde.

  The choice of aldehyde governs the nature of

  a-alkylidene substituent. For example, when the acyl

  lactone corresponds to the formula I, 1a-alkylidene-y-

  Butyrolactone obtained has the formula: R,

R 4 CHR '

R. 0-

  (III) wherein R1, R2, R3, R4 and R 'are as defined above. When the? -Acyl-lactone has the formula II, the? -Alkylidene-b-valerolactone has the formula: R o

R3 CHR '

  (IV) wherein R1, R2, R3, R4, R5, R6 and R 'are as previously defined. In a particularly useful embodiment of the invention, the radical R 'of the aldehyde and the corresponding α-alkylidene-lactone represents hydrogen, C 1-8 alkyl or alkenyl, C 3-8 cycloalkyl or cycloalkenyl, phenyl , substituted phenyl, benzyl or substituted benzyl. Suitable substituents on phenyl or benzyl groups include C 1-8 alkyl, nitro, halogen (Cl or Br),

  hydroxyl, carboxyl and carboalkoxy.

  For the reaction, it is necessary to use an alkali metal hydroxide with the α-acyl lactone and the aldehyde. Suitable alkali metal hydroxides include sodium hydroxide, potassium hydroxide and lithium hydroxide. The alkali metal hydroxide can be used in the state or in aqueous solution. While it is not necessary to add water to the reactants, it is generally believed that the presence of a certain amount of water in the reaction mixture is advantageous. Since the alkali metal hydroxides are hygroscopic, there is usually sufficient water associated therewith for the reaction. In addition, a quantity

  additional water is formed during the reaction.

  However, if the alkali metal hydroxide is added as an aqueous solution, the amount of water used is such that it does not exceed 50% by volume of the reaction mixture. More typically, if water is added, it constitutes from about 1% to about 25% by volume of the water.

reaction mixture.

  The reaction is carried out at a temperature in the range of 50 C to 150 C using an inert solvent as the reaction medium. Any solvent that is liquid and substantially inert under the reaction conditions can be used. Examples of solvents are benzene, toluene, xylene, pentane, hexane, heptane, octane, isooctane, cyclohexane, ethylbutyl ether, diethyl acetal, dipropyl acetal, dibutyl acetal and the like. . The inert solvents which form with the water an azeotrope, in particular an azeotrope which boils in the temperature range of 50 ° C. to 95 ° C., are particularly suitable. The volume ratio of solvent to reactants may range from about 1: 1 to 20: 1, but in general it is from 2: 1 to 8: 1. Benzene, toluene, xylene and cyclohexane are particularly advantageous solvents because of their ability to form azeotropes and the fact that

that they are readily available.

  The way to add reactants is not critical. All the reactants can be combined at the beginning of the reaction, or, as is generally the case, two of the reactants can be combined and the other reactants are added continuously or successively. For example, the alkali metal hydroxide may be added to a mixture of α-acyl lactone and aldehyde. In a particularly advantageous embodiment, the α-acyl lactone and the alkali metal hydroxide are combined and at least partially reacted prior to the addition of the aldehyde to the mixture. With this procedure, a portion of the α-acyl lactone is converted to the alkali metal salt. This preliminary reaction is

  suitably carried out by refluxing the α-acyl-

  lactone and alkali metal hydroxide in a suitable solvent while removing water. The azeotropic reflux and azeotropic removal of water are typically carried out at a temperature in the range of 50 ° C. to C. When the distillation slows down, usually when about 60 to 75 percent of the theoretical amount of water is The aldehyde is removed and the mixture is refluxed until substantially all the water formed during the reaction is removed. When the water is removed, the temperature of the reaction mixture increases to the highest possible value with the solvent used. In general, the temperature of the reaction mixture is maintained between about 75 ° C. and 125 ° C. at this stage of the reaction. If desired, the temperature can be increased by distilling off the original solvent and adding an inert solvent to the desired extent.

higher boiling point.

  Substantially equimolar amounts of the reactants are used to optimize the yield of α-alkylidene lactone. A slight molar excess can be used, which in general does not exceed 20%, and preferably less than 10%, which may be advantageous depending on the method used to combine the reactants. For example, when the α-acyl lactone and the alkali metal hydroxide are pre-reacted to form the alkali metal salt, a molar excess of the aldehyde of 10% to 15% is

often desirable.

  The alkylidene group present at the α-position of the lactone ring is hydrogenated by conventional hydrogenation techniques which do not reduce the carbonyl group and do not cause ring opening. The catalyst and conditions used for the hydrogenation are chosen so that only the unsaturation of the alkylidene group

is reduced.

  The hydrogenation can be carried out using heterogeneous or homogeneous catalysts which cause a cis or trans addition of hydrogen on the carbon-carbon double bond. The hydrogen pressures can be between 1 and 30 bar. Although it is not necessary, the hydrogenation can be carried out in an inert solvent. Hydrogenation can take place at

  temperatures between about 0 C and about 120 C.

  However, the temperature is generally between 25 ° C and about 85 ° C. Examples of solvents that may be used include methanol, ethanol, propanol, isopropanol, n-butanol, tbutanol, octanol, ethyl-2-hexanol, toluene, benzene, and the like. , xylene, acetonitrile, dimethylformamide, tetrahydrofuran, diethyl ether and the like. The solvent may be the

  same as that used for the reaction of a-acyl-

  lactone, alkali metal hydroxide and aldehyde, in which case the α-alkylidene lactone can be hydrogenated directly without isolating it, ie without removing the solvent. However, if desired, the α-alkylidene-lactone can be isolated prior to hydrogenation. The crude product can be hydrogenated or the lactone can be purified. Heterogeneous catalysts are preferably used which comprise supported catalysts based on palladium, platinum, nickel and rhodium in which the metal is present on the support in an amount from 1 to

  % by weight, and more preferably from 2 to 10% by weight.

  Preferred catalysts include palladium on carbon, palladium on calcium carbonate, palladium on barium sulfate, platinum on carbon, platinum on calcium carbonate and platinum on barium sulfate. Other suitable catalysts include platinum oxide, palladium oxide, platinum black, nickel on alumina, nickel on kieselguhr, Raney nickel, rhodium on aluminum oxide and the like. The amount of supported metal catalyst used can be from 0.025 to 10% by weight, and preferably from 0.05 to 5% by weight, based on the α-alkylidene lactone. Homogeneous catalysts that can be used include tris (triphenylphosphine) rhodium chloride in C6H6-EtOH, dichlorotris (triphenylphosphine) ruthenium in C6H6 and tris (triphenylphosphine) rhodium chloride in the presence of triethylsilane. In general, when the hydrogenation is complete, the α-alkyl-lactone is recovered after removal of the catalyst. When a heterogeneous catalyst is used, which is a preferred embodiment of the invention, this is typically done by filtration or decantation. When a solvent is used for the hydrogenation, it is generally removed by evaporation to recover the product which can then be

  purify by distillation, recrystallization or the like.

  The α-alkylated derivatives correspond to the formulas: R. R. R H

- CFR.

R3 0 and CHR '

R 1 \ R

O R1

(V) (VI)

  in which R1, R2, R3, R4, R5, R6 and R 'are such that

previously defined.

  The invention will be better understood on reading the following nonlimiting examples. In the examples, percentages and parts are by weight unless otherwise indicated. EXAMPLE Preparation of α-acetyl-lactone Sodium hydroxide (100 g / 400 g of water) was introduced into a one liter four-necked flask equipped with an ice bath, a mechanical stirrer, a dry ice condenser, a thermometer and a dropping funnel. Ethyl acetoacetate (325 g, 2.5 moles) and propylene oxide (174 g, 3.0 moles) were mixed and introduced into the dropping funnel. The vessel was cooled to 15 ° C and the mixture of ethyl acetoacetate and propylene oxide was added at a temperature below 20 ° C over a period of two hours. The reaction mixture was then stirred for six hours and transferred to a separatory funnel and acidified with 225 ml of concentrated hydrochloric acid. The two layers were separated and the bottom aqueous layer was extracted three times with diethyl ether. The combined extracts were dried over sodium sulfate and the diethyl ether was removed at room temperature.

  using a Rotovap at 70 C (pressure of the water pump).

  The resulting product was distilled using a packed column and a Perkins triangular head. Fractions 1-3 (94 g) contained mainly ethyl acetoacetate. A fourth fraction (170 g) boiling at 112-117 ° C at 933 Pa (7 torr) contained substantially 100% of the desired α-acetyl lactone, 3-acetyl-5-methyldihydro-2 (3H) -furanone. Conversion of α-acetyl-lactone to α-alkylidene-lactone: 3-Acetyl-5-methyldihydro-2 (3H) -furanone (28.4 g, 0.200 moles) was combined with 200 ml of toluene in a 500 ml flask equipped with a mechanical stirrer, a Dean-Stark trap and a dropping funnel. Eight grams (0.200 moles) of sodium hydroxide were added and the mixture was stirred at room temperature for ten minutes and then refluxed for one hour for a period of

  which water was removed in the Dean-Stark trap.

  Cyclohexanecarboxaldehyde (25.7 g, 0.225 moles) was then slowly added dropwise to the reaction mixture over a period of about one hour. The mixture was refluxed for a further four hours and then cooled to room temperature and washed three times.

  with 100 ml of water and then dried over sodium sulfate.

  Filtration and then evaporation of toluene, which was the solvent, gave 35 g of crude α-alkylidene lactone, 3-cyclohexylmethylene-5-methyldihydro-2 (3H) -furanone. The crude product was distilled off with a 1 × 20 cm Vigreaux column to obtain 20.8 g of cyclohexylmethylene-5-methyldihydro-2 (3H) -furanone (94% by gas-liquid chromatography). (GLC), 50% yield) (boiling range 105134 ° C at 26 Pa (0.20 mm Hg)). The structure of the product was confirmed by proton nuclear magnetic resonance and carbon: 1HRMN (CDCl3) δ 6.57 (m, 0.37H), 6.0 (m, 0.63H), 4.6 (m, 1H) ), 3.44 (m, 0.53H), 3.1 (m, 1H), 2.47 (m, 1H), 2.19;

  (m, 0.47H), 1.87-0.9 (series of complex multiplets 13H).

  13CRM (CDC13) È 171.309, 170, 148.981, 145.260, 124.788,

  123.087, 73.990, 73.696, 39.393, 36.870, 35.766, 32.726,

  32,550, 32,441, 31,515, 31,434, 25,869, 25,738, 25,396,

22.223, 21.775.

  Gas-liquid chromatographic analysis showed that the product comprised 66.7% Z-isomer and 33.3% E-isomer. Hydrogenation of the α-alkyne-lactone to α-alkyl-lactone: In a 25-liter flask ml equipped with a magnetic stirrer and closed by a rubber stopper

  introduced 3-cyclohexylmethylene-5-methyldihydro-2 (3H) -

  furanone (6 g, 0.031 mol), 0.5 g of catalyst consisting of 5% platinum on carbon and 8 ml of ethanol. To introduce hydrogen there was provided a syringe needle which passed through the plug and penetrated the reaction mixture. A second syringe needle connected to an oil bubbler was also provided which passed through the stopper without dipping into the reaction mixture. The mixture was stirred at room temperature and hydrogen was introduced at a moderate rate for 15 hours. The mixture was then filtered through diatomaceous earth to remove the catalyst. Ethanol was removed under pressure

  reduced to collect 6.1 g of product (99% yield).

  3-cyclohexylmethyl-5-méthyldihydro-2 (3H) -furanone. The product crystallized on standing and was recrystallized from a 1: 1 ethanol / water mixture to obtain a substantially pure product which melted at 68-69 ° C. The structure of the product was confirmed by nuclear magnetic resonance

proton.

  1HRMN (CDCl3) δ 4.48 (m, 1H), 2.6 (m, 2H), 2.0-0.75

  (series of complex multiplets with a doublet at 1.4, 17H).

ExempleIl

  To demonstrate the multiple possibilities of the process and the ability to obtain lactones having an n-alkylidene group at the α-position, Example I was repeated except that heptaldehyde was substituted for cyclohexanecarboxaldehyde. Distillation of the reaction mixture yielded 3-heptylidene-5-methyldihydro-2 (3H) -furanone in a yield of 54.5% (boiling range 113-120 ° C. under 6 Pa (0.05 mmHg). The structure of the product was confirmed by proton nuclear magnetic resonance: 1HRMN (CDCl3) δ 6.55 (m, 0.66H), 6.04 (m, 0.34H), 4.6

  (m, 1H), 3.0-1.85 (series of complex multiplets, 4H), 1.44-

  1.0 (multiplet with a triplet at 1.25, 11H), 0.75 (triplet

deformed, 3H).

  When the reaction was repeated using potassium hydroxide as the base, the reaction proceeded without difficulty although at a slightly higher rate.

  low to produce 3-heptylidene-5-methyldihydro-2 (3H) -

  furanone. Using the general hydrogenation procedure described in Example I, 3-heptylidene-5-methyldihydro-2 (3H) furanone (10 g, 0.051 mole) was combined with 0.5 g of catalyst consisting of % of palladium on carbon and with 10 ml of ethanol. Hydrogen was bubbled into the mixture for 12 hours with stirring. After removal of the catalyst and evaporation of the solvent, 9.95 g (96% by GLC,% yield) of 3-heptyl-5-methyldihydro-2 (3H) furanone were obtained. The proton nuclear magnetic resonance spectrum of the product was as follows: 1HRMN (CDCl3) δ 4.47 (m, 1H), 2.53 (m, 2H), 2.01.1 (series

  multiplets with a doublet at 1.42, 16H), 0.89 (t, 3H).

Example III

  Example I was repeated using heptaldehyde, 3-acetyl-5-ethyldehydro-2 (3H) -furanone and sodium hydroxide to give the alkylidene-γ-butyrolactone.

  corresponding. The product, 3-heptylidene-5-ethyldihydro-

  2 (3H) -furanone, boiled in the range 113-118 ° C (7 Pa (0.06 mm Hg)) and had the following proton nuclear magnetic resonance spectrum: HRMN (CDCl3) δ 6.7 (tt, 0) , 42H), 6.2 (tt, 0.58H), 4.42

  (m, 1H), 3.1-0.8 (series of complex multiplets, 20H).

  The product thus prepared was hydrogenated following the general procedure described in Example I. For the

  reaction, 2.1 g of 3-heptylidene-5-

  ethyldihydro-2 (3H) -furanone (0.010 mole) with 0.1 g of 5% palladium on carbon and 5 ml of ethanol, and hydrogen was slowly indroduced for one and a half hours. After removal of the catalyst and evaporation of

  solvent, 2.0 g of 3-heptyl-5-ethyldihydro-

  2 (3H) -furanone (97% minimum concentration, 95% yield).

  1 HRMN (CDCl 3) δ 4.28 (m, 1H), 2.5 (m, 2H), 2.0-1.1 (series of

  complex multiplets, 14H), 1.0 and 0.89 (two triplets, 6H).

Exemole IV

  To demonstrate the ability to prepare a-methylene

  y-butyrolactone, 3-acetyl-5-butyldihydro-

  2 (3H) -furanone with sodium hydroxide and paraformaldehyde according to the procedure of Example I. 3-Methylene-S5butyldihydro-2 (3H) -furanone was obtained which boiled at 87 ° C. (26 Pa ( 0.2 mmHgH) with a yield of 70%.

  The proton nuclear magnetic resonance and carbon spectra were as follows: 1HRMN (CDCl3) δ 6.2 (very close triplet, 1H), 5.64 (very close triplet, 1H), 4.55 (pentet, 1H), 3.1

  (m, 1H), 2.6 (m, 1H), 1.9-1.15 (m, 6H), 0.91 (t, 3H).

  13CRMN (CDCl3) b 170.368, 134.993, 121.712, 77.656, 35.979,

33,550, 26,999, 22,414, 13,919.

  In a reactor, 3-methylene-5-

  butyldihydro-2 (3H) -furanone (5.8 g, 0.33 mol) with 0.25 g of 5% palladium on carbon and 6 ml of ethanol. The mixture was stirred at room temperature and hydrogen was slowly introduced under the surface for eight hours. The catalyst was removed by filtration and the solvent was removed by evaporation under reduced pressure to obtain 5.3 g of 3-methyl-5-butyldihydro-2 (3H) -furanone

  (minimum concentration 84%, yield 85.6%).

  1HRMN (CDCl3) 54.34 (m, 1H), 2.6 (m, 2H), 1.9-1.1 (series of complex multiplets with a doublet at δ 1.25, 10H), 0.9

(t, 3H).

Eemple v

  3-Phenylmethylene-5-butyldihydro-

  2 (3H) -furanone by reacting 3-acetyl-5-butyldihydro-

  2 (3H) -furanone with sodium hydroxide and benzaldehyde according to the procedure described in Example I. The crude product (64.5% yield) was collected by distillation of the reaction mixture at 25-147 ° C ( 5 Pa (0.04 mm Hg)) to remove light ends. The structure has been confirmed

  by proton nuclear magnetic resonance.

  1 HRMN (CDCl 3) δ 7.5 (m, 6H), 4.56 (pentet, 1H), 3.3 (ddd,

  1H), 2.8 (ddd, 1H), 1.9-1.2 (m, 6H), 0.86 (t, 3H).

  The reaction was repeated using 3-acetyl-

  dihydro-2 (3H) -furanone, sodium hydroxide and

  benzaldehyde to produce 3-phenylmethylene dihydro-

  2 (3H) -furanone. The yellow crude solid obtained from the reaction was recrystallized from chloroform to give 3-phenylmethylenedihydro-2 (3H) -furanone, a yellow crystalline solid which melts at 116 C. Proton nuclear magnetic resonance and carbon spectra were: 1 HRMN (CDCl 3) δ 7.526 (t, 1H, J = 3 Hz), 7.45 (m, 5H), 4.42 (t, 2H, J = 7.6 Hz), 3.208 (dt, 2H, J = 7.6, 3.0Hz) 13CRMN (CDCl3) b 172.455, 136.414, 134.598, 129.963,

  129.805, 128.904, 123.685, 65.447, 27.368.

  3-Phenylmethylene-5-butyldihydro-2 (3H) - was combined

  furanone (5.95 g, 0.026 mol) with 0.28 g of 5% palladium on carbon and 8 ml of ethanol and was carried out

  hydrogenation for eight hours in the usual way.

  After removal of the catalyst and the solvent,

  collected 6.0 g of 3-benzyl-5-butyldihydro-2 (3H) -furanone.

  The structure of the product has been confirmed by resonance

protonic magnetic.

  1HRMN (CDCl3) b 7.25 (m, 5H), 4.30 (m, 1H), 3.35-1.10 (series)

  of complex multiplets, 11H), 0.83 (t, 3H).

  Examples VI and VII Two reactions were carried out according to the process of the invention using valeraldehyde. For a reaction (Example VI), 3-acetyl-dihydro-2 (3H) -furanone was used and for the second reaction (Example VII) 3-acetyl-5-n-butyldihydro-2 (3H) was used. furanone. For both reactions, sodium hydroxide and toluene were used as the solvent, and the reactants were present in substantially equimolar amounts. We have

  obtained by the respective reactions 3-pentylidene-

  dihydro-2 (3H) -furanone (86-104 C at 13.3 Pa (0.1 mm Hg)) and 3-pentylidene-5-n-butyldihydro-2 (3H) -furanone (110-131 ° C under 1, 33 Pa (0.01 mm Hg)). The proton magnetic resonance spectra for the products were as follows: 3-pentylidene-dihydro-2 (3H) -furanone: 1HRMN (CDCl3) 1 6.7 (m, 0.93H), 6.26 (m, 0, 07H), 4.4 (t, 2H), 2.9 (m, 2H), 2.22 (m, 2H), 1.4 (m, 4H), 0.9

(t, 3H).

  3-pentylidene-5-n-butyldihydro-2 (3H) -furanone: 1HRMN (CDCl 3) δ 6.7 (tt, 0.4H), 6.2 (tt, 0.6H), 4.45 (m, 1H), 3.1-1.5 complex multiplets, 14H), 0.9 (two

superimposed triplets, 6H).

  Hydrogenation of 3-pentylidene-5-n-butyldihydro-2 (3H) -

  furanone leads to 3-pentyl-5-n-butyldihydro-2 (3H) -

furanone.

  Example VIII Methyl-2-butyraldehyde was reacted with 3-acetyl-5-ethyldihydro-2 (3H) -furanone and the hydroxide of

  sodium to obtain 3- (1-methylpropyl) methylene-5-

  Ethyldihydro-2 (3H) -furanone (88% by GLC). The product.

  boiled in the range of 80-94 C at 26 Pa (0.2 mm Hg) and had the following proton nuclear magnetic resonance spectrum: 1HRMN (CDCl3) 6.5 (td, 0.22H), 5.92 ( td, 0.78H) 3, 4.4

  (m, 1H), 3.67-0.76 (complex multiplet series, 16H).

  Hydrogenation of 3 - (1-methylpropyl) methylene-5 -

  Ethyldihydro-2 (3H) -furanone leads to 3- (2-methylbutyl) -

  ethyldihydro-2 (3H) furanone. To further demonstrate the multiple possibilities of the process, the procedure of Example II was repeated except that for the first step of the reaction, cyclohexane was used as the solvent. After eight hours (total reaction time) the reaction was stopped and

  collected the crude product consisting of 3-heptylidene-5-

  Methyldihydro-2 (3H) -furanone in the usual manner (45.6% yield). Hydrogenation of the product leads to

  3-heptyl-5-methyldihydro-2 (3H) furanone.

  Example I was repeated using propionaldehyde diethyl acetal as azeotropic solvent for the reaction. For the reaction, 100 ml of propionaldehyde diethyl acetal was introduced into the reactor with 14.9 g (0.10 mole) of 3-acetyl-5-methyldihydro-2 (3H) furanone. The mixture was stirred and 4 g (0.10 mole) of powdered sodium hydroxide was added. The mixture was stirred for 10 minutes and then refluxed for five and a half hours after which 14.0 g (0.125 mole) of cyclohexanecarboxaldehyde was added over a period of one hour. The mixture was refluxed for a further twelve hours, cooled and processed to yield 19 g of crude 3-cyclohexylmethylene-5-methyldihydro-2 (3H) -furanone (59% yield). The structure of the product has been confirmed by

  proton nuclear magnetic resonance and carbon.

  Hydrogenation of the product to obtain the a-alkyl-

  corresponding lactone can be carried out according to the procedure of Example I or by using other

  conventional hydrogenation techniques.

  EXAMP X p-nitrobenzaldehyde was reacted with 3-acetyl-5-butyldihydro-2 (3H) -furanone. For the reaction, 9.21 g (0.05 mole) of furanone and 7.55 g (0.05 mole) of p-nitrobenzaldehyde were combined with 2.5 g (0.065 mole)

  of sodium hydroxide in 25 ml of water and 25 ml of ethanol.

  A reaction occurred immediately. The light yellow solid was collected by filtration and washed at room temperature.

  ethanol. It was confirmed that this was the 3- (p-

  nitrophenyl) methylene-5-butyldihydro-2 (3H) furanone by

  magnetic-nuclear resonance of carbon.

  Hydrogenation of the product according to the procedure

  usually leads to 3- (p-nitrobenzyl) -5-butyldihydro-

2 (3H) -furanone.

Example XII

  To demonstrate the ability to change the mode

  hydrogenation procedure, the 3-heptylidene

  2-methyl-dihydro-2 (3H) -furanone prepared according to the general procedure of Example I. For the reaction, it was introduced into a stainless steel Parr autoclave at

  high pressure of 3-heptylidene-5-methyldihydro-2 (3H) -

  furanone (650 g, 1.21 mol) with 0.055 g of a 5% palladium on carbon catalyst. The reactor was placed under a relative pressure of 400 psig (2758x103 Pa) with hydrogen and maintained at 85-90 ° C for 20 hours with stirring. Additional hydrogen was added to maintain the pressure. After completion of the reaction, the mixture was filtered to remove the catalyst and distilled under vacuum. The fraction removed between 130 ° C and 147 ° C (666 Pa (5 mm Hg)), which solidified on cooling, was recrystallized from methanol / water to give 3-heptyl-5-methylene-2 (3H). ) -furanone (melting point)

34.5 ° C-35.5 ° C).

R3VEDI CATIONS

  A process for preparing α-alkyl-γ-butyrolactones of formula V:

K3 & CHR '

R1 \ 0

  CV) in which R1, R2, R3, R4 and R 'are selected from the group consisting of hydrogen and a hydrocarbon radical having from 1 to 20 carbon atoms, characterized in that it comprises: (1) the reaction at a temperature in the range of 50 ° C to 150 ° C and in an inert solvent, with removal of the water of reaction, substantially equimolar amounts of an α-acyl lactone of formula I: RR Hi 9

3 4 CR *

  In which R1, R2, R3 and R4 represent hydrogen or a hydrocarbon radical having 1 to 20 carbon atoms and R * is a C1-C8 alkyl group, an aldehyde of formula R'CHO wherein R 'is hydrogen or a hydrocarbon radical having 1 to 20 carbon atoms and an alkali metal hydroxide, and: (2) hydrogenating the product obtained in step (1) under conditions that do not reduce the carbonyl group and that

  do not cause an opening of the cycle.

  2. Method according to claim 1, characterized in that the hydrocarbon radicals R1, R2, R3 and R4 are chosen from the group consisting of C1-C8 alkyl, C3-C6 cycloalkyl, phenyl, alkyl-substituted phenyl radicals.

  C1-8, benzyl and benzyl substituted with C1-8alkyl.

  3. Method according to claim 2, characterized in that the hydrogenation is carried out under a pressure of 1 to 30 bar and at a temperature of 0 C to 120 C using 0.025 to 10% by weight of a catalyst supported heterogeneous platinum, palladium, nickel or ruthenium, said metal being

  present on the support in an amount of 1 to 15% by weight.

  4. Method according to claim 2, characterized in that in step (1) the α-acyl lactone and the alkali metal hydroxide are combined and reacted before the addition.

aldehyde.

  5. Method according to claim 4, characterized in that the aldehyde is added after elimination of about 60 to

% of the theoretical amount of water.

  6. Process for the preparation of α-alkyl-5-valerolactones of formula VI: R. H R e e CHR '

R O

  in which R 1, R 2, R 3, R 4, R 5, R 6 and R 'are chosen from the group formed by hydrogen and a hydrocarbon radical containing from 1 to 20 carbon atoms, characterized in that it comprises: (1) reacting, at a temperature between 50 ° C and C and in an inert solvent with removal of the water of reaction, substantially equimolar amounts of an α-acyl lactone of formula II:

O; 0

R CR *

R3 H

R R

(II)

  in which R 1, R 2, R 3, R 4, R 5 and R 6 are hydrogen or hydrocarbon radicals having 1 to 20 carbon atoms and R 1 is a C 18 alkyl group, an aldehyde of formula R 'CHO in which R 'is hydrogen or a hydrocarbon radical having 1 to 20 carbon atoms, and an alkali metal hydroxide, and (2) hydrogenating the product obtained in step (11) under conditions which do not do not reduce the carbonyl group and

  do not cause an opening of the cycle.

  7. Process according to claim 6, characterized in that the hydrocarbon radicals R1, R2, R3, R4, R5 and R6 are chosen from the group formed by C1-C6 alkyl, C36-cycloalkyl, phenyl and alkyl-substituted phenyl radicals. in

  C 1-8, benzyl and benzyl substituted with C 1-8 alkyl.

  8. Process according to claim 7, characterized in that the hydrogenation is carried out under a pressure of 1 to 30 bar and at a temperature of 0 ° C. to 120 ° C. using 0.025 to% by weight of a heterogeneous catalyst. supported platinum, palladium, nickel or ruthenium, said metal being

  present on the support in an amount of 1 to 15% by weight.

  9. Process according to claim 8, characterized in that in step (1) the α-acyl lactone and the alkali metal hydroxide are combined and reacted before the addition.

aldehyde.

  10. Process according to claim 9, characterized in that the aldehyde is added after the elimination of approximately 60% to

  75% of the theoretical amount of water.