KR0128106B1 - Process for producing cyclopentenone with catalyst of indenglcobalt(i) compound - Google Patents

Abstract

In the reaction of alkene or alkyne such as norbonadien or norbonylene with carbon monoxide, the pressure of carbon monoxide is fixed at 5-100 atmosphere, and the temperature is maintained at 50-200 degree Celsius.Indenyl cobalt(I) compound is used as catalyst, and cyclopentenone derivatives are synthesized.

Description

Method for preparing cyclopentenone derivatives using indenyl cobalt (I) compound as catalyst

The present invention relates to a method for preparing a cyclopentenone derivative used as an intermediate for making a useful compound such as a pharmaceutical or a perfume.

A conventional organic chemical approach to preparing cyclopentenone derivatives is to cyclocondensate by base catalyst of 1,4-diketone derivatives as shown in the following [I].

However, in the method for producing a cyclopentenone derivative by such a method, it is not only simple to obtain a 1,4-diketone derivative, but more conceptually simple methods have been studied because these compounds are not diverse. That is, Organic Reactions (1991) No. 40, Journal of American Chemical Society (1989) 111, No. 3336, Journal of Organic Chemistry (1992) No. 57, 5803, Joumal of Amerecan Chemical Society (1988) No. 110, 1286, As described in page 2044 of Organometalics (1992) No. 11, there have been studies on the reaction as described in the following [2] for synthesizing cyclopentenone derivatives by cyclizing alkene, alkyne and carbon monoxide together using a transition metal.

However, these reactions required the same amount (1 equivalent) of the transition metal as the reactants, which made it difficult to utilize them for industrial mass production. Recently, a method of synthesizing cyclopentenone derivatives using triphenylphosphate as dicobaltoctacarbonyl and coligand has been disclosed in Journal of American Chemical Society (1994) 3159. In this case, too, the number of conversion of the catalyst is small and a large amount of catalyst is required, and the reaction proceeds only when the pressure of carbon monoxide is constant at 3 atm.

SUMMARY OF THE INVENTION An object of the present invention is to provide a production method for industrially mass-producing cyclopentenone derivatives with high yield and low cost by using indenyl cobalt (I) compounds catalyst. .

The method for producing a cyclopentenone derivative according to the present invention can be classified into one of an intermolecular reactions and one of an intramolecular reactions.

First, the synthesis of cyclopentenone derivatives through intermolecular reactions is made by reacting alkenes, alkynes and carbon monoxide under an indenyl cobalt (I) compound catalyst as shown in [3] below.

Herein, alkenes are preferably reactive norbonadiene and norbonylene, and in the case of nolvadiene, the cyclopentenone derivatives synthesized are 1, 1, or 3 of the organocopper compound as shown in Reaction [4]. Useful four-addition reactions and retro Diels-Alder reactions make useful stereoselective cyclopentenone derivatives.

In Formula [3], R ¹ and R ² of alkyne are hydrogen, alcohol, amine thiol, ether, arene, alkyl; Or hydrocarbons unconjugated with the triple bond of the alkyne, substituted with one or more of alcohol, ammonium, thiol, ether, arene, alkyl, carboxylic acid, aldehyde, ketone, nitrile, amide double bond, triple bond Compound.

In general, in the cyclopentenone derivatives synthesized, R ¹ , that is, the functional group attached to the carbon next to the carbonyl group is larger than R ² , and when R ¹ and R ² are similar in size, there is no regioselectivity, so R ³ , R ^{When a tetravalent} same nolvonadiene is used as the alkene, a mixture of the following two cyclopentenone derivatives is obtained.

As a special embodiment of the synthesis of cyclopentenone derivatives by intermolecular reaction, a method of synthesizing cyclopentenone derivatives by reacting alkene and alkyne in a molecule with a catalyst of carbon monoxide and indenyl cobalt (I) Synthesis of cyclopentenone derivatives via intermolecular reaction. Such intramolecular reactions are generally easier than synthesizing cyclopentenone derivatives by the intermolecular reactions described above, and produce bicyclic cyclopentenon derivatives as a result of the reaction as shown in Equation [5]. .

The catalyst used in the method for preparing a cyclopentenone derivative according to the present invention is an indenyl cobalt (I) compound. Indenyl cobalt (I) ligands can be easily separated off such as alkanes, carbon monoxide, phosphine, phosphite, alkynes, amines, and the like, such as indenylcobaltocene It is also possible to be easily made of indenyl cobalt (I) under the reaction conditions. Among the indenyl cobalt (I) compounds containing the ligand, compounds which are easy to make and stable are indenylco (Co (CO) ₂ and indenylCo (PPh ₃ ) ₂ each having two carbon monoxide and triphenylphosphine as ligands. And indenylCo (COD) having 1, 5-cyclooctadiene (COD) as a ligand.

In the method for producing a cyclopentenone derivative according to the present invention, carbon monoxide is supplied in a gaseous state, and the supply pressure thereof may be 5 to 100 atm, and is preferably supplied at a pressure of 15 to 50 atm.

Solvents that may be used in the preparation method of the cyclopentenone derivatives according to the present invention include benzene, toluene, xylene, hexane, heptane, octane, chloroform (CHC1 ₃ ), methylene chloride (CH ₂ Cl ₂ ), and ethylene chloride (dichloroethane). ), Diethyl ether, butyl ether, ethyl acetate, acetonitrile (CH ₃ CN), THF (tetrahydrofurane), DME (1, 2-dimeth-oxyethane) DMF (dimethylformamide), DMSO (dimethylsulfoxide) dicream (diglyme diethylene) glycol dimethylether) is possible, but DME is most preferred.

In the method for preparing a cyclopentenone derivative according to the present invention, the reaction [1] is possible at a temperature of 50 ° C. to 200 ° C., but the temperature is preferably 100 ° C. to 110 ° C.

Hereinafter will be described with respect to an embodiment of a method for producing a cyclopentenone derivative according to the present invention.

'Example I' of the method for producing a cyclopentenone derivative according to the present invention is a method for preparing a cyclopentenone derivative by an intermolecular reaction. Alkenes used in this example were nolvonadienes which are easy to make the cyclopentenone derivatives obtained as a result of the reaction into stereoselective useful cyclopentenone derivatives as described above, and all alkynes used terminal alkynes. In this example, the equivalent ratio of alkyne, alkene and catalyst is 1: 5: 0.01, and the yield is 85-100% as shown in Table 1.

Meanwhile, 'Example II' is a method for preparing a cyclopentenone derivative by intramolecular reaction using an arylpropargyl amine in which alkene and alkyne are contained in one molecule. 0.02 and the yield is more than 90%.

Example I

Intermdecular reaction

Into the reaction vessel, 2.7 ml (25 mmol) of nolvondane, 5 mmol of alkyne shown in Table 1, and 10 ml of dimethoxy ethane (DME) are added as a solvent. After bubbling nitrogen to remove the air in the vessel, 14 mg (0.05 mmol) of catalyst endenyl cobalt (I) is added. The pressure of carbon monoxide is 10 atm to remove nitrogen from the vessel and fill the vessel with carbon monoxide. Here, the pressure of carbon monoxide is 15 atm, and the mixture is stirred at a temperature of 100 to 110 ° C. for about 40 hours.

After completion of the reaction, the gas is first discharged, and then the solvent and residual nolvadiene are removed by a rotary evaporator, and the product is obtained by silica gel column chromatography or vacuum distillation. Yield based on the purity and alkyne yield of the product after drying is shown in Table 1 below.

TABLE 1

Example II

Intramolecular reaction

Into the reaction vessel, 1.25 g (5.0 mmol) of aryl propargylamine protected with tosyl group and 10 ml of DME as a solvent were removed, followed by bubbling with nitrogen to remove air, followed by catalyst indenyl cobalt (I) [indenylCo]. (COD)] 28 mg (0.1 mmol). 10 atm of carbon monoxide was added to the vessel to remove nitrogen, and the pressure of carbon monoxide was set to 15 atm, followed by stirring at a temperature of 100 to 110 ° C for about 40 hours.

After reaction reaction, the product is obtained by silica gel column chromatography. After drying the product is 1.30 g.

The yield based on arylpropargylamine is 94%.

The method for preparing a cyclopentenone derivative according to the present invention uses an indenyl cobalt (I) compound catalyst to greatly increase the number of conversion of the catalyst compared to the method for preparing a cyclopentenone derivative, and thus yields a small amount of catalyst. This high level can be used for industrial mass production of cyclopentenone derivatives which are used as intermediates in the manufacture of useful compounds such as pharmaceuticals and perfumes.

Claims (8)

A method for producing a cyclopentenone derivative from alkynes, alkenes and carbon monoxide, wherein the indenyl cobalt (I) compound is used as a catalyst. The method of claim 1, wherein the alkene is nolvadiene or nolvylene. The method for producing a cyclopentenone derivative according to claim 1, wherein the alkyne is represented by the following formula. R ¹ -C ≡ C-R ² Wherein R ¹ and R ² are hydrogen, alcohol, amine, thiol, ether, arene, alkyl; or alcohol, amine, thiol, ether, arene, alkyl, carboxylic acid, aldehyde, ketone, nitrile, amide, double A hydrocarbon compound non-conjugated with a triple bond of the alkyne, substituted with at least one of a bond and a triple bond) The method of claim 1, wherein the alkene and alkyne are present in one molecule. The method for producing a cyclopentenone derivative according to claim 1, wherein the pressure of the carbon monoxide is 5 atm to 100 atm. The method of claim 5, wherein the carbon monoxide has a pressure of 15 to 50 atm. The method for producing a cyclopentenone derivative according to claim 1, wherein the reaction is performed at a temperature of 50 ° C to 200 ° C. The method of claim 7, wherein the reaction is carried out at a temperature of 100 ℃ to 110 ℃.