JPH111452A - Production of 2-(2-phenyl-2-propenyl)indane-1,3-dione compounds - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily obtain the subject compound useful as an intermediate for medicines or agricultural chemicals in a high yield by reacting an indane-1,3- dione compound with a benzene compound and allene in the presence of a base and a palladium catalyst. SOLUTION: An indane-1,3-dione compound of formula I (R<1> is H, a lower alkyl, etc.; R<2> , R<3> are each H, a halogen, a lower alkyl) (e.g. 2-ethylindane-1,3- dione) is reacted with a substituted benzene compound of formula II (A is Br, I, etc.; X<1> , X<2> are each H, a halogen, a lower alkyl, etc.), (e.g. m- bromochlorobenzene) with allene in the presence of 0.5-5 equivalents, preferably 1.0-3.0 equivalents, of a base (e.g. potassium carbonate) and a palladium catalyst (e.g. bistriphenylphosphine palladium dichloride) in a solvent (e.g. dimethylformamide) in a volume of 1-30 times, preferably 3-30 times, that of the compound of formula II at 20-90 deg.C, preferably 50-80 deg.C, to obtain the objective compound of formula III.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION The present invention relates to a process for producing indane-1,3-diones, and particularly useful as a pharmaceutical or an intermediate for agrochemicals described in JP-A-2-304043. -(2-phenyl-2-propenyl) indan-1,3-diones.

[0002]

2. Description of the Related Art Conventionally, a method for producing 2- (2-substituted-2-propenyl) indan-1,3-diones is represented by a reaction formula (1).

[0003]

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[0004] Indane-1,3-diones represented by the general formula [I '] (wherein R ⁶ represents a lower alkyl group or the like) are represented by the general formula [IV] (where Y is chlorine , A bromine atom, a halogen atom such as iodine, an alkylsulfonyloxy group, a phenylsulfonyloxy group, a hydroxyl group, or R ⁷ CO ₂ (wherein R ⁷
Represents a lower alkyl group or a lower alkoxy group. A production method is known in which a compound represented by)) is reacted in the presence of a base, under an acid catalyst, or under a palladium catalyst. General formula
The method for synthesizing the compound represented by [IV] is described in JP-A-2-304043,
Japanese Unexamined Patent Publications Nos. 7-061945, 7-264058, 8-
001322, and a method described in Japanese Patent Application No. 7-338940.

[0005]

As described above, 2- (2-phenyl-2-propenyl) indan-
In the case of synthesizing 1,3-diones, other industrially useful production methods have been desired, for example, because the number of steps is large and the yield is not a satisfactory method. The present invention solves the conventional problems and provides 2- (2-phenyl-2-propenyl) indan-1,3.
-To provide a method for producing diones selectively, efficiently and with high yield.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the conventional problems, and as a result, as a method for producing 2- (2-substituted-2-propenyl) indan-1,3-diones. -1,3-diones represented by the general formula [I] and the general formula
A benzene represented by the formula [II] is reacted with an allene in the presence of a base and a palladium catalyst to obtain a compound represented by the general formula
2- (2-phenyl-2-propenyl) indane-1,3-characterized in that the target compound represented by [III] is obtained in good yield.
The present inventors have found a method for producing dione, which has led to the present invention. That is, the gist of the present invention is represented by the general formula [I]

[0007]

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Wherein R ¹ is a hydrogen atom, a lower alkyl group,
Represents a lower alkenyl group and a lower alkynyl group, R ² and
R ³ each independently represents a hydrogen atom, a halogen atom, or a lower alkyl group. ), Indane-1,3-diones have the general formula [II]

[0009]

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(Where A is a bromine atom, an iodine atom, OSO ₂
R ⁴ (in the formula, R ⁴ represents a halogen atom, a lower alkyl group optionally substituted by halogen, an allyl group optionally substituted), or OP ((O) (OR ⁵ ) ₂ (formula Wherein R ⁵ represents a lower alkyl group or an allyl group), and X ¹ and X ² each independently represent a hydrogen atom, a halogen atom, a lower alkyl group, or a lower haloalkyl group. Wherein the substituted benzene represented by the formula) is reacted with an allene in the presence of a base and a palladium catalyst [III]

[0011]

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(Wherein R ¹ , R ² , R ³ , X ¹ and X ² are a general formula
As defined in (I) and (II). )) To produce 2- (2-phenyl-2-propenyl) indan-1,3-diones.

[0013]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred specific embodiments of the present invention will be described below. In the indane-1,3-diones represented by the general formula (I), R ¹ represents a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group.
Lower alkyl group of C ₁ -C ₄ as groups, such as methyl, ethyl, n- propyl and n- butyl. Examples of the lower alkenyl group include a C ₂ -C ₄ alkenyl group, specifically, a vinyl group, an allyl group, and a butylene group. The lower alkynyl group includes a C ₂ -C ₄ alkynyl group, specifically, an ethynyl group, a propargyl group and the like. Among them, a methyl group, an allyl group, a propargyl group, and a benzyl group are preferred. R ² and R ³ are each independently a hydrogen atom, a chlorine atom, a halogen atom such as a bromine atom, a C ₁ -C ₄ alkyl group, specifically a methyl group, an ethyl group, an n-propyl group, an n- Shows a butyl group and the like. Among them, a methyl group and a chlorine atom are preferable.

In the benzenes represented by the general formula [II], A is a bromine atom, an iodine atom, OSO ₂ R ⁴ or OP (= O) (O
R ⁵ ) ₂ is indicated. R ⁴ represents a halogen atom such as a fluorine atom, a lower alkyl group optionally substituted with halogen, or an allyl group optionally substituted. As the lower alkyl group,
C ₁ represents an alkyl group -C _4, as is R ^4, a methyl group, an ethyl group, n- propyl group, n- butyl group, and their halogen substituents, trifluoromethyl group and the like, for example. Examples of the optionally substituted allyl group include a phenyl group, a p-methylphenyl group, and a p-chlorophenyl group.

The lower alkyl group for R ⁵ includes a C ₁ -C ₄ alkyl group such as a methyl group, an ethyl group, an n-propyl group and an n-butyl group. Examples of the allyl group include a phenyl group. X ¹ and X ² are each independently a hydrogen atom, a chlorine atom, a halogen atom such as a fluorine atom, a methyl group, an ethyl group, a n-propyl group, a C _{1 to} C ₄ alkyl group such as an n-butyl group, C ₁ such as trichloromethyl group and trifluoromethyl group
A haloalkyl group of ~C _3. Among them, at least one is preferably a halogen atom, particularly preferably substituted at the meta position with respect to A 1, and more preferably a chlorine atom.

The allene used in the method of the present invention can be charged in several portions during the reaction. Further, it can be continuously blown into the reaction system in a gas state. In order to suppress a side reaction, a method of continuously blowing is preferable.
Allen is a commercially available gaseous substance, and Organic synthesis V.
It may be prepared from 2,3-diclocloben as described in 22.

The indan represented by the general formula (I)
-1,3-diones and benzenes represented by the general formula (II)
Any base can be used for the reaction together,
Specifically, NaOH, KOH, K_TwoCO_Three, NaCO_Three, NaH and other inorganic salts, NaPO
_Four, K_ThreePO_FourEtc. phosphate, NaOR ^Five, KOR^Five(Where R^FiveIs C₁~ C₆of
(Indicating an alkyl group) such as triethylamine and pyridine
But not limited to these.
No. The amount of the base subjected to the reaction is not particularly limited.
But 0.5 to 5 equivalents, preferably 1.0 to 3.0 equivalents
You.

As the palladium catalyst used for the reaction, zero-valent and divalent palladium catalysts are used. Specifically, Pd (dppe) (dppe represents (diphenylphohino) ethane), Pd (PPh ₃ ) ₄ , PdCl ₂ (PPh) ₂ , Pd ₂ (dba) ₃ (dba is dibe
represents a nzylideneacetone), PdZ ¹ ₂ (wherein Z ¹ represents a chlorine atom, a bromine atom, an iodine atom, an acetoxy group.)
Pd [P (Ph-Z ² ) (Ph-Z ³ ) (Ph-Z ⁴ )] ₄ (wherein Z ² , Z ³ and Z ⁴ represent a sulfonic acid or a hydrogen atom, but Z ² = Z ³ = Z ⁴ = hydrogen atom), but are not limited thereto. These catalysts can be used alone, but PPh ₃ , dba, dppe, P (Ph-Z ² ) (Ph-Z ³ ) (Ph-Z ⁴ ) (where Z ² , Z ³ , Z ⁴ Can be used in the co-presence of a compound which can be a ligand such as described above). Although the amount of the palladium catalyst is not particularly limited, it is 0.001 to 0.1 equivalent,
Preferably it is 0.001-0.05 equivalent.

In the present invention, a solvent is generally used, and specific examples thereof include DMF, THF, DMSO, acetone, acetonitrile, toluene, water and the like. However, it is not limited to these. These solvents may be used as a mixture of two or more solvents. The amount of the solvent is not particularly limited, but it is 1 to 30 times, preferably 3 to 20 times the amount of the compound represented by the formula (II) used in the reaction.

The present invention can be carried out in the presence of a phase transfer catalyst. Examples of the phase transfer catalyst include onium salts such as quaternary ammonium salts and quaternary phosphonium salts, and crown compounds. Specifically, quaternary phosphonium salts include tetraethylphosphonium chloride, tetraethylphosphonium bromide, tetraethylphosphonium iodide, and the like, and quaternary ammonium salts include tetrabutylammonium chloride, tetrabutylammonium bromide, and tetrabutylammonium iodide. , Triethylbenzylammonium bromide, tetrabutylammonium hydrogen sulfate and the like.
18-crown-6, dicyclohexyl-18-crown-6 and the like. The amount of the phase transfer catalyst used for the reaction is not particularly limited, but is preferably 0.01 to 0.1 equivalent, preferably
0.005 to 0.02 equivalents.

[0021] The reaction temperature in the present invention is preferably in the range of 20 to 90 ° C, especially 50 to 80 ° C. After completion of the reaction, inorganic substances in the system are removed by a method such as filtration or washing with water, and then the solvent is distilled off, followed by crystallization to obtain the desired product. Crystallization can also be performed by adding water to the reaction system to obtain the desired product. Water-soluble such as P (Ph-Z ² ) (Ph-Z ³ ) (Ph-Z ⁴ ) (where Z ² , Z ³ and Z ⁴ are as described above) when rinsing with water or crystallizing from an aqueous solvent By dissolving the ligand in water, palladium remaining in the system can be removed.

[0022]

EXAMPLES The present invention will be described in more detail with reference to examples and comparative examples, but the present invention is not limited to the following examples unless it exceeds the gist. Example 1 Preparation of 2- [2- (3-chlorophenyl) -2-propenyl] -2-ethylindane-1,3-dione 8.71 g (0.05 mol) of 2-ethylindane-1,3-dione, m- 9.58 g (0.05 mol) of bromochlorobenzene, potassium carbonate 2
A mixed solvent of 0.8 g (0.15 mol), 0.32 g (0.001 mol) of tetrabutylammonium bromide, 0.07 g of bis (triphenylphosphinepalladium (II) dichloride, and 60 ml of DMF was heated to 80 ° C., and Organic synthesis V was added under a nitrogen stream. p2
Allene generated by the method described in 2 was blown for 30 minutes. After allowing the reaction system to cool, 60 ml of water was added and stirred, and the mixture was left to stand.The lower aqueous layer was removed.60 ml of water and 0.2 g of a compound obtained by sulfonating triphenylphosphine were added. Crystallization was performed while adding 30 ml and stirring, and the precipitated crystals were collected by filtration, dried and dried with 2- [2- (3-chlorophenyl) -2-.
8.10 g of [propenyl] -2-ethylindane-1,3-dione were obtained. Further, ethyl acetate was added to the mother liquor to perform extraction, the organic layer was concentrated, and hexane was added to the obtained residue for crystallization to give 2- [2
-(3-Chlorophenyl) -2-propenyl] -2-ethylindane
3.29 g of -1,3-dione was obtained.

[0023]

As described above in detail, according to the production method of the present invention, 2- (2-substituted-2-yl) useful as an intermediate for medicines and agricultural chemicals is used.
Propenyl) indane-1,3-dione can be easily obtained in high yield.

Claims (2)

[Claims] 1. A compound of the general formula [I] (In the formula, R ¹ represents a hydrogen atom, a lower alkyl group, a lower alkenyl group and a lower alkynyl group, and R ² and R ³ each independently represent a hydrogen atom, a halogen atom, or a lower alkyl group.) General formula for indane-1,3-diones
[II] embedded image (Where A is a bromine atom, an iodine atom, OSO ₂ R ⁴ (wherein R ⁴
Represents a halogen atom, a lower alkyl group optionally substituted by halogen, or an allyl group optionally substituted by halogen. ) Or OP (= O) (OR ⁵ ) ₂ (wherein R ⁵ is a lower alkyl group,
Indicates an allyl group. ) And X ¹ and X ² each independently represent a hydrogen atom, a halogen atom, a lower alkyl group, or a lower haloalkyl group. ), And
General formula [III] characterized in that allene is reacted in the presence of a base and a palladium catalyst. (Wherein, R ¹ , R ² , R ³ , X ¹ and X ² represent the general formulas (I) and (II)
As defined in. ), A method for producing 2- (2-phenyl-2-propenyl) indan-1,3-diones. 2. The method according to claim 1, wherein the reaction is performed in the presence of a phase transfer catalyst.