JPS6045606B2 - Method for producing ketones - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an efficient method for producing ketones, and more particularly to a method for producing ketones by acylating an organic halide with carbon monoxide and an organotin compound.

Methods using various metal carbonyls or anionic metal carbonyls are known as methods for producing ketones by converting the halogen atoms of organic halides into acyl groups, but all of them require a stoichiometric amount as a reagent. In addition to requiring a stoichiometric amount of metal carbonyl, the former method does not allow asymmetric ketones to be obtained in good yields, and the latter method requires complicated operations for preparing the reagents.

Furthermore, a method is known in which 1,3-dithiane or 1,3-oxazine is alkylated using an alkyl halide as a starting material, but since organic lithium and Grignard reagents are also used in the reaction, protection of functional groups is a problem. Not only does it have serious drawbacks, but it also has problems such as a long reaction process and limitations on the types of halides that can be used. As a result of extensive research to overcome the drawbacks and problems of these conventional methods, the present inventors have discovered that organic halides can be produced using organometallic compounds and carbon monoxide in the presence of an appropriate metal or metal complex catalyst. It was discovered that the objective could be achieved by carbonylating the compound, and based on this knowledge, the present invention was accomplished.

That is, the present invention relates to the general formula R" good.

Further, X represents a halogen atom. ) and the general formula R, SnY. -m (R" in the formula represents an alkyl group, an aryl group, an aralkyl group, a cycloalkyl group, an alkenyl group, or a heterocyclic group, and these organic groups may have a substituent. Also, Y is Indicates an organic group selected from a halogen atom or an alkyl group, an aryl group, an aralkyl group, a cycloalkyl group, an alkenyl group, a heterocyclic group, and those in which a substituent is introduced into these organic groups. m is 1 is an integer of ~4, and multiple R2 or Y may themselves be the same or different from each other, and may further form a ring structure with Sn.l5R.)
A compound of the general formula 1-CO-R2 (wherein R1 and R2 are the same as above), which is characterized by reacting an organic tin compound represented by the formula with carbon monoxide in the presence of a palladium catalyst.
The present invention provides a method for producing ketones represented by The organic halides used in the method of the present invention are not particularly limited, and those represented by the general formula A1X above can be arbitrarily applied, but particularly preferred are those having a hydrogen atom at the β-position relative to the halogen atom. Although it does not have a saturated carbon atom, the method of the present invention is of course also applicable to a saturated carbon atom having a hydrogen atom at the β position.

Further, these organic halides may be substituted with various polar functional groups. Examples of the organic halides include aromatic halides such as iodobenzene and bromobenzene, substituents having a functional group on the aromatic nucleus, halomethyl derivatives such as benzyl chloride, ethyl bromoacetate, phenacylbromide, and iodomethyl, and β -bromostyrene, β-bromovinylmethylketone, iodoethylene, β
- In addition to unsaturated halides such as phenylethynyl bromide, heterocyclic halides in which a halogen atom is bonded to furan, thiophene, and pyrrole, and their functional group substituted products, iodoethyl, α-phenylethyl bromide, α −
Examples include alkyl or aralkyl halides such as ethyl bromopropionate. Furthermore, in the organotin compound used in the present invention, there are no limitations on the organic group, including alkyl groups such as methyl, ethyl, propyl, and butyl groups, aryl groups such as phenyl and tolyl groups, vinyl,
Examples include unsaturated hydrocarbon groups such as propenyl and β-phenylethynyl groups, allyl groups, and benzyl groups, and these organic groups may be substituted with functional groups.

These organotin compounds can be easily synthesized by conventional methods such as reactions between corresponding metals and halides, hydrometalation reactions between corresponding metal hydrides and ethylenically unsaturated compounds, and metalation reactions between aromatic compounds and metal salts. Can be synthesized. In the method of the present invention, the reaction proceeds in the absence of a solvent or in a solvent,
As the solvent, benzene, ether, tetrahydrofuran, hexamethylphosphotriamide, dimethylformamide, acetone, hexane, acetonitrile, etc. are preferably used, and water, alcohol, primary or secondary amines, carboxylic acids, etc. Commonly used protons can be used, except those that serve as active proton sources.

Further, the partial pressure of carbon monoxide in the method of the present invention may be normal pressure or lower, but is usually in the range of 1 to 100 atm, preferably in the range of 1 to (a) atm.

The carbon monoxide used may be diluted with an inert gas such as nitrogen or methane. The reaction of the present invention can be advantageously carried out in the presence of a palladium catalyst.

Such palladium catalysts include metal palladium such as palladium black and palladium on carbon, and zero-valent palladium complexes such as tetrakistriphenylphosphine palladium, dibenzylideneacetone palladium, carbonyltristriphenylphosphine palladium, and bistriphenylphosphine palladium maleate anhydride. , divalent palladium salts or complexes such as dichlorbistriphenylphosphine palladium, dichlorbistriphenylphosphine palladium, dipromobistriphenylsin palladium, palladium chloride, palladium acetate, bisacetatobistriphenylphosphine palladium, iodophenyl bistri Examples include organic or hydrogenated palladium complexes such as phenylphosphine palladium, chlorobenzoylbistriphenylphosphinepalladium, iodomethylbistributylphosphinepalladium, dimethylbisdiphenyphorphosphinepalladium, dihydridobistricyclohexylphosphinepalladium, etc. Any such precursor can also be used as long as it reacts with the organic hydride in the reaction system to produce an organic palladium compound. In addition, these catalysts include phosphine, phosphite, phosphinite, tertiary amine, pyridine,
A ligand such as bipyridyl may be added and used in the reaction. In the method of the present invention, the molar ratio of organic halide to organic tin compound is usually in the range of 10:1 to 1:10, preferably in the range of 2:1 to 1:2. Also, the molar ratio of organic halide and carbon monoxide is usually 1:1 to 1.
:50, preferably 1:1 to 1:15. Furthermore, there is no limit to the amount of palladium catalyst used, but for organic halides, it is generally sufficient under the formula P. Depending on the structure of the organic halide, the reaction in the method of the present invention may proceed at room temperature, but in order to obtain a preferable reaction rate, it may be heated up to 200°C, and the preferred reaction temperature is usually 50°C to 150°C. is within the range of The ketone compound produced by the reaction of the present invention can be separated and purified by distillation after removing unreacted substances and by-products from the reaction solution using a conventional method. In the method of the present invention, a wide variety of organic halides and organic tin compounds can be used, and various ketones, whether symmetrical or asymmetrical, can be obtained in good yields.

Further, the reaction operation is easy because it does not require complicated operations and does not use reactive raw materials such as organolithium or Grignard reagents, and the desired ketone can be easily obtained.
Next, the present invention will be explained in more detail based on examples.

Example 1 C6H5Pdl[P(C6H5)l↓10・5m9(
1.25×10 1), 3 mt of hexamethylphosphortriamide as a solvent, 0.84 mt of iodobenzene
(7.5w0n01) and tetrabutyltin 1.23m
1 (3.757 m01) was charged and reacted at 120°C under a carbon monoxide pressure of 30 atm.

Although the substantial pressure drop stopped after about 4 hours, heating and stirring was continued overnight. After that, the reaction solution was evaporated into 50ml of ether.
1, washed with water, then treated with potassium fluoride to remove tin halide by filtration, further washed with water, dried over magnesium sulfate, concentrated, and distilled to yield 441 m9.
of valerophenone was obtained. This corresponds to a yield of 73% based on the number of moles of tetrabutyltin charged. The results are shown in the table below. Examples 2 to 32 Various ketone compounds were synthesized in the same manner as in Example 1 using the specified halides and organotin compounds under the reaction conditions shown in the table below.

Claims (1)

[Scope of Claims] 1 General formula R^1X (R^1 in the formula represents an alkyl group, an aryl group, an aralkyl group, a cycloalkyl group, an alkenyl group, or a heterocyclic group, and these organic groups have a substituent. In addition, an organic halide represented by the general formula R_■Sn_4-_m (wherein R^
2 represents an alkyl group, an aryl group, an aralkyl group, a cycloalkyl group, an alkenyl group, or a heterocyclic group, and these organic groups may have a substituent. Further, Y represents an organic group selected from an alkyl group, an aryl group, an aralkyl group, a cycloalkyl group, an alkenyl group, a heterocyclic group, and those obtained by introducing a substituent into these organic groups. m is 1 to 4
is an integer of , and the plurality of R^2 or Y may themselves be the same or different from each other, and furthermore, Sn and R
_■ may form a ring structure. ) and generalized carbon in the presence of a palladium catalyst.
- A method for producing ketones represented by R^2 (where R^1 and R^2 are the same as above).