JPS6116375B2 - - 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. As a method for producing ketones by converting the halogen atom of an organic halide into an acyl group, methods using various metal carbonyls or anionic metal carbonyls are known, but in either case, stoichiometric amounts of the reagents are used. Not only does the former method require a metal carbonyl, but the asymmetric ketone cannot be obtained in good yield with the former method, and the latter method requires complicated operations for the preparation of the reagent. Furthermore, using alkyl halides as starting materials, 1,3-dithiane and 1,3
-Although methods for alkylating oxazines are known, they use organolithium, Grignard reagents, etc. for the reaction, which not only has serious drawbacks in terms of protection of functional groups, but also requires a long reaction process. There were problems such as limitations on the halides that could be used. As a result of intensive research to overcome the drawbacks and problems of these conventional methods, the present inventors have discovered that organic halogens can be synthesized using organotin compounds and carbon monoxide in the presence of an appropriate metal or metal complex catalyst. The inventors have discovered that the objective can be achieved by carbonylating a compound, and based on this knowledge, the present invention has been accomplished. That is, according to the present invention, ^the general formula R ¹ represents a halogen atom selected from chlorine and iodine) and an organic halogen compound represented by the general formula R ² ₄ Sn (R ² in the formula represents an alkyl group or an aralkyl group, and these organic groups have a substituent. A plurality of R ² may be the same or different.) and carbon monoxide are reacted in the presence of a nickel catalyst. A method for producing ketones represented by the general formula R ¹ -CO-R ² (wherein R ¹ and R ² have the same meanings as above). is provided. In the above-mentioned organic halide (general formula ^{R 1} May contain. Examples of organic halides include alkyl or aralkyl halides such as iodoethyl, α-phenylethyl bromide, and ethyl α-bromopropionate; aromatic halides such as iodobenzene and bromobenzene; and aromatic halides with functional groups in the aromatic nucleus. halomethyl derivatives such as benzyl chloride, α-methylbenzyl bromide, ethyl bromoacetate, phenacyl bromide, iodomethyl, heterocyclic halides in which a halogen atom is bonded to furan, thiophene, and pyrrole, and functional group substituted products thereof, etc. can be given. Furthermore, in the organic tin compound used in the present invention, examples of organic groups include alkyl groups such as methyl, ethyl, propyl, and butyl groups, and aralkyl groups such as benzyl groups. It may be replaced. These organotin compounds can be easily synthesized by conventional methods such as reaction between tin and halides, hydrometalation reaction between tin hydride and ethylenically unsaturated compounds, and metalation reaction between aromatic compounds and tin salts. . In the method of the present invention, the reaction proceeds in the absence of a solvent or in a solvent, and examples of solvents include hexane, benzene, ether, tetrahydrofuran, hexamethylphosphortriamide, dimethylformamide,
Acetonitrile, acetone, etc. are preferably used, and commonly used ones can be used, excluding those that serve as active proton sources such as water, alcohol, primary or secondary amines, and carboxylic acids. . Further, the partial pressure of carbon monoxide in the method of the present invention may be lower than normal, but is usually in the range of 1 to 500 atm, preferably in the range of 10 to 300 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 nickel catalyst. As such a nickel catalyst, a complex in which part or all of nickel carbonyl and its coordinating carbon monoxide is substituted with a Lewis base such as phosphine or arsine can be suitably used, and specific examples thereof include: Ni(CO) ₃ PPh ₃ , Ni(CO) ₂ (PPh ₃ ) ₂ ,
Ni(CO)( _PPh3 ) ₃ , Ni( _PPh3 ) ₄ , Ni(CO) ₂
(AsPh ₃ ) ₂ , Ni(CO) ₂ {Ph ₂ p(CH ₂ )nPPh ₂ }(n
=2-10), Ni(CO) ₂ (1,1'-bisdiphenylphosphinoferrocene), and the like. Precursors that easily convert into these complexes in the reaction system may also be used, examples of which include NiCl ₂ (PPh ₃ ) ₂ , NiCl ₂ (AsPh ₃ ) ₂ , NiBr ₂
(1,1'-bisdiphenylphosphinoferrocene) and the like. Furthermore, these precursors may be reacted by combining a suitable nickel salt that easily forms in the system with a Lewis base. Examples of the nickel salt include divalent inorganic nickel salts such as NiCl ₂ and NiBr ₂ , Ni( Organic acid nickel salts such as OCOCH ₃ ) ₂ ,
Examples of Lewis bases include various phosphines, diphosphines, and arsines. 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. The molar ratio of organic halide to carbon monoxide is usually in the range of 1:1 to 1:500, preferably in the range of 1:1 to 1:50. Furthermore, although there is no limit to the amount of nickel catalyst used, it is generally sufficient to use 1/30 or less of the amount of organic halide. Furthermore, the reaction in the method of the present invention may proceed at room temperature depending on the structure of the organic halide, but in order to obtain a preferable reaction rate, it may be heated up to 300°C, and the preferred reaction temperature is usually 50°C to 200°C. is within the range of The ketone compound produced by the reaction of the present invention is
After removing unreacted substances and by-products from the reaction solution by a conventional method, it can be separated and purified by distillation. In the method of the present invention, a wide variety of organic halogen compounds 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 organic lithium 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 Ni(CO) ₂ (PPh ₃ ) ₂ , 5.63×10 ^-2 mmol, hexamethylphosphorotriamide 1.5 ml as a solvent, and iodobenzene were placed in a stainless steel (SUS316) autoclave with an internal volume of 27 ml under a nitrogen atmosphere. 3.75mmol and tetramethyltin
Prepare 1.88 mmol, under 20 atmospheres of carbon monoxide pressure,
The mixture was heated and stirred at 120°C overnight. After that, the reaction solution was poured into 50 ml of ether, washed with water, dried over magnesium sulfate, concentrated, and distilled.
Obtained with a yield of 78%. Examples 2 to 10 Various ketone compounds were synthesized in the same manner as in Example 1 using predetermined halides and organotin compounds under the reaction conditions shown in the table below. The results are shown in the same table. Note that the yield was measured by gas chromatography. Values in parentheses indicate isolated yields.

[Table] Example 11 Desoxybenzoin was obtained in a yield of 82% as a result of carrying out the reaction in the same manner as in Example 1 except that tetrabenzyltin was used instead of tetramethyltin. Example 12 The reaction was carried out in the same manner as in Example 1 except that benzyl chloride was used instead of iodobenzene, and as a result, phenylacetone was obtained with a yield of 58.1%.

Claims (1)

[Claims] ¹ General formula R ¹ (Indicates the selected halogen atom.)
An organic halogen compound represented by and the general formula
R ² ₄ Sn (R ² in the formula represents an alkyl group or an aralkyl group, and these organic groups may have a substituent. Also, multiple R ² may be the same or different from each other. General formula R ¹ −CO−R ² characterized by reacting an organic tin compound represented by ) with carbon monoxide in the presence of a nickel catalyst.
A method for producing ketones represented by the formula (wherein R ¹ and R ² have the same meanings as above).