JPH0796518B2 - Method for producing diaryl ketone - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to general formula [I] ArCOAr ′ [I] (wherein Ar and Ar ′ represent a substituted or unsubstituted aromatic group or heteroaromatic group). Represents a diaryl ketone.

According to the method of the present invention, pharmaceuticals [“Pharmaceutical Synthesis Manual”, volumes 1 to 4, CMC, (1988)] Various diaryl ketones useful as synthetic intermediates can be synthesized. In addition, a polyfunctional diaryl ketone useful as a highly selective oxidant for steroids can be efficiently synthesized [Chem. Soc. Rev., 1, 553 (197
2)]. Furthermore, it is possible to synthesize various industrially important diaryl ketones as photopolymerization initiators and dye sensitizers [“Application of new and fully functional polymers” CMC (1988)].

[Prior art]

Conventionally, the synthesis method of diaryl ketone has been the Friedel-Crafts reaction [“Fri
edel-Crafts and Related Reactions "Vol III, Chap 3
1, Intersciense, New York (1964); “Friedel-Crafts
Chemistry "Wiley-Interscience, New York (197
3)], a method of condensing an aromatic hydrocarbon to carbon tetrachloride [“Organic Sythesis” Coll. Vol. 1, 95 (1948)], a Fries rearrangement reaction [“F
riedel-Crafts and Related Reaction "Vol.III, Chap3
3, Intersciense, New York (1964)], condensation reaction of aromatic magnesium and cadmium compounds with aromatic compounds ["Organic Functional Group Preparation" Vol I, Cha
p 8, Academic, New York (1983)], a method of reacting an aromatic tin compound with an aromatic halide in the presence of a transition metal catalyst and carbon monoxide [Chem. Abstr., 95 , 114980m].
Is disclosed.

[Problems to be Solved by the Invention]

Among these methods, the method (1) limits the substrates that can be used and has low reaction selectivity. Method is difficult to synthesize an asymmetric diaryl ketone. In addition, since the method (1) uses an active organometallic compound, it is necessary to protect it when using a substrate having a functional group.
In the method (1), the substrates that can be used are extremely limited.

As described above, the conventional production methods are limited in the compounds that can be used, and it is difficult to say that they are practical for industrially producing diaryl ketones having many functional groups.

[Means for Solving the Problems]

The inventors of the present invention have investigated the industrially easy production method of a diaryl ketone having a functional group, excluding such drawbacks, and as a result, have shown that the general formula [II] Ar-SiR _m X _3-m [II] (wherein , Ar represents a substituted or unsubstituted aromatic group or heteroaromatic group, R represents an alkyl group or the above Ar group, X
Represents a halogen or an alkoxy group, m represents any of 0.1.2.3) and a silyl group-substituted aromatic compound represented by the general formula [III] Y-Ar '[III] (wherein Ar' is a substituent). Or an aromatic compound represented by an unsubstituted aromatic group or a heteroaromatic group, and Y represents a leaving group) in the presence of a Group VIII transition metal catalyst, carbon monoxide and a fluoride ion source. It was found that the diaryl ketone represented by the general formula [I] ArCOAr '[I] (wherein Ar and Ar' have the same meanings as described above) can be obtained by the reaction, and the present invention has been completed. Is.

The silyl group-substituted aromatic compound represented by the general formula [II] which is the raw material of the present invention is a method of reacting various aromatic metal compounds with chlorosilane [Synthesis., 841 (197
9)] A method of reacting sidirane with an aryl halide in the presence of a palladium catalyst [J. Organomet. Chem., 128, 40.
9 (1977)], and various structures are easily available industrially.

Examples of the silyl group-substituted aromatic compound that can be used include 3-fluorophenyl (methyl) difluorosilane, 4-fluorophenyl (methyl) difluorosilane, 4-bromophenyl (methyl) difluorosilane, and 3-bromophenyl (dimethyl ) Fluorosilane,
3-chlorophenyl (methyl) difluorosilane, bis (3-chlorophenyl) difluorosilane, 3-methoxyphenyl (ethyl) difluorosilane, 4-methoxyphenyl (ethyl) difluorosilane, 3-trifluoromethylphenyl (ethyl) difluorosilane, 4-trifluoromethyl (ethyl) difluorosilane, 4-trifluoromethylphenyl (propyl) difluorosilane, 3-methylphenyl (ethyl) difluorosilane,
4-methylphenyl (ethyl) difluorosilane, 2-
Methylphenyl (propyl) difluorosilane, 3-cyanophenyl (ethyl) difluorosilane, 2-methoxycarbonyl (ethyl) difluorosilane, 3-carboxyphenyl (ethyl) difluorosilane, phenyl (ethyl) difluorosilane, phenyl (propyl) difluoro Silane, phenyl (methyl) difluorosilane, phenyl (trimethyl) silane, phenyl (trifluoro) silane, phenyl (trichloro) silane, phenyl (methyl) dichlorosilane, phenyl (triethyl) silane, 1-naphthyl (trimethyl) silane, 1 −
Naphthyl (ethyl) difluorosilane, 2-naphthyl (ethyl) difluorosilane, 2-thienyl (ethyl)
Difluorosilane, 2-thienyl (methyl) difluorosilane, 2-thienyl (trimethyl) silane, 2-thienyl (trifluoro) silane, 2-thienyl (trichloro) silane, 3-thienyl (ethyl) difluorosilane, 2-pyridyl ( Ethyl) difluorosilane, 2-pyridyl (methyl) difluorosilane, 3-pyridyl (ethyl) difluorosilane, quinolin-2-yl (ethyl) difluorosilane, quinolin-3-yl (ethyl)
Difluorosilane, 2-furyl (ethyl) difluorosilane, 2-furyl (propyl) difluorosilane, phenyl (methyl) dimethoxysilane, 1-naphthyl (ethyl) dimethoxysilane, 2-thienyl (ethyl) diethoxysilane, 2-thienyl (Methyl) dimethoxysilane and 2-pyridyl (ethyl) diethoxysilane can be mentioned.

The aromatic compound represented by the above general formula [III], which is the other raw material, is a compound that is industrially easily available, and when exemplified including a leaving group, 4-iodoanisole, 4-iodoethoxybenzene, 4 -Ethoxyphenyl trifluoroacetate, 2-iodoanisole, 2-bromoanisole, 2-ethoxyphenyltrifluoroacetate, 4
-Chloroanisole, 4-bromoanisole, 2-ethoxyphenyl (phenyl) sulfide, 2-iodobenzyl alcohol, 3-iodobenzyl alcohol, 3-
Hydroxymethyl (phenyl) sulfide, 4-iodobenzyl alcohol, 4-hydroxymethyl (phenyl) sulfide, 2-bromobenzyl alcohol, 3-
Bromobenzyl alcohol, 2-chlorobenzyl alcohol, (2-chlorophenyl) dimethyl phosphate,
Phenyl diethyl phosphate, 3-iodophenylacetic acid, 3-iodophenylethyl acetate, 3-iodobenzyl acetate, 4-iodobenzyl acetate, 3-bromobenzyl acetate, 4-bromobenzyl acetate, 1-naphthyl (methyl) sulfide, 1 -Naphthyl (phenyl) sulfide, phenyl triflate, 1-benzyl triflate, phenyl mesylate, phenyl (methyl) sulfide, 1-benzyl (methyl) sulfide, 1-benzyl mesylate, 2-benzyl triflate, 4-tolyl mesylate, 2-cyanophenyl (phenyl) ether,
2-iodobenzonitrile, 3-iodobenzonitrile, 4-iodobenzonitrile, 2-bromobenzonitrile, 3-bromobenzonitrile, 3-cyanophenyl (phenyl) ether, 4-bromobenzonitrile, 2
-Acetoxyiodobenzene, 3-acetoxyiodobenzene, 4-acetoxyiodobenzene, 2-acetoxybromobenzene, 4-iodoacetophenone, 3-iodoacetophenone, 2-iodoacetophenone, 4-
Iodophenol, 3-iodophenol, 2-iodophenol, methyl 4-iodobenzoate, methyl 3-iodobenzoate, methyl 2-iodobenzoate, 4-iodobenzaldehyde, 3-iodobenzaldehyde, 2-
Iodobenzaldehyde, 1-iodonaphthalene, 2-
Iodonaphthalene or the like can be used.

The present invention is an essential condition to carry out in the presence of a fluoride ion source. As a fluoride ion source, tris (diethylamino) sulfonium difluorotrimethyl silicate, (TASF), tris (dimethylamino) sulfonium difluorotrimethyl silicate, tris (dimethylamino) sulfonium bifluoride, tetrabutylammonium fluoride, benzyltrimethylammonium Onium fluoride salts such as fluoride and benzyltriethylammonium fluoride, and metal fluorides such as cesium fluoride, rubidium fluoride and potassium fluoride can be used. The amount used can be a catalytic amount or an excessive amount with respect to the silyl group-substituted aromatic compound, but it is preferable to use 0.8 to 2.0 molar amount.

Examples of the VIII metal catalyst used include Pd (0) complexes such as palladium tetrakis (triphenylphosphine), palladium benzalacetone complex, palladium dibenzalacetone chloroform complex, allyl palladium chloride dimer, and palladium bis (trichloride) chloride. Phenylphosphine),
Pd (II) complexes such as phenylpalladium bis (triphenylphosphine) iodide and benzylpalladium bis (triphenylphosphine) chloride, Ni (0) such as tetrakis (triphenylphosphine) nickel, nickel bis (triphenylphosphine) chloride Ni (II) complexes such as and tetrakis (triphenylphosphine) platinum
Pt (0) complexes can be used. The amount used may be a so-called catalytic amount.

The present invention is an essential condition to carry out in the presence of carbon monoxide. Although the reaction can be carried out within the range of 1.0 to 50 atm of carbon monoxide, 1.0 to 3.0 atm is preferable because of easy operation.

The present invention is preferably carried out in a solvent, and particularly preferably carried out in an aprotic polar solvent from the viewpoint of reaction efficiency. For example, dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, 1,3-dimethylperhydropyrimidin-2-one, hexamethylphosphoric triamide, tetrahydrofuran, acetonitrile, N, N-dimethylimidazolidinone (DMI) alone, Alternatively, they can be mixed and used. The reaction can be carried out in the range of 50 ° C to 200 ° C, but 50 ° C to 120 ° C is preferable because of easy operation.

Hereinafter, the present invention will be described in more detail with reference to Examples.

Example 1 Allyl palladium chloride dimer 1.8 mg (0.005 mmol), 4-iodoacetophenone 50 under carbon monoxide atmosphere of 1 atm
mg (0.20 mmol) and potassium fluoride 19 mg (0.33 mmol)
56 mg (0.30 mmol) of 4-lyl (ethyl) difluorosilane was added to the DMI (1 ml) solution of and the mixture was stirred at 100 ° C. for 3 hours.
The reaction solution was passed through column chromatography (silica gel, hexane: ethyl acetate = 10: 1) to remove the solvent.
The obtained crude product was further purified by column chromatography (silica gel, hexane: ethyl acetate = 10: 1) to give 4-acetyl-4′-methylbenzophenone 43 mg.
Got Yield 91%. ¹ H-NMR (CDCl ₃ ): δ2.45 (S, 3H), 2.63 (S, 3H), 7.28
(D, J = 7.5Hz, 2H), 7.70 (d, J = 7.5Hz, 2H), 7.80 (d, J
= 8.0Hz, 2H), 8.04 (d, J = 8.0Hz, 1H). IR (KBr): 1690,1645,1605,1290,1265,930,860,830,760
cm ^-1 . Example 2 According to the same experimental procedure as in Example 1, 35 mg of potassium fluoride
(0.60 mmol) and allyl palladium chloride 1.8 mg (0.005
mmol), 3-methoxyphenyl (propyl) difluorosilane 65 mg (0.30 mmol) and 3-iodobenzaldehyde 46 mg (0.20 mmol) were reacted to give 3-formyl-3′-methoxybenzophenone 38 mg. Yield 80
%. ¹ H-NMR (CDCl ₃ ): δ3.92 (S, 3H), 7.04-7.80 (m, 5
H), 8.00-8.73 (m, 3H), 10.08 (S, 1H). IR (neat): 3100,2850,2750,1700,1660,1290,1245,104
0,800,740 cm ^-1 . Example 3 In the coexistence of 35 mg (0.60 mmol) of potassium fluoride and 1.8 mg (0.005 mmol) of allyl palladium chloride dimer, 65 mg (0.30 mmol) of 3-methoxyphenyl (ethyl) difluorosilane and 1- Iodonaphthalene 51
mg (0.20 mmol) is reacted, and 3-methoxyphenyl 1-
35 mg of naphthyl ketone was obtained. Yield 67%. ¹ H-NMR (CDCl ₃ ): δ3.80 (S, 3H), 7.05-7.77 (m, 8
H), 7.80-8.25 (m, 3H). IR (neat): 3100,2950,1660,1590,1585,1280,1260,103
5,780,745 cm ^-1 . Example 4 In the presence of potassium fluoride (35 mg, 0.60 mmol) and allyl palladium chloride dimer (1.8 mg, 0.005 mmol), phenyl (ethyl) difluorosilane 52 was prepared by the same experimental procedure as in Example 1.
mg (0.30 mmol) and 4-iodoastphenyl 46 mg
(0.20 mmol) was reacted to give 4-cyanobenzophenone 25
to obtain mg. Yield 60%. ¹ H-NMR (CDCl ₃ ): δ 7.20-8.00 (m, 9H). IR (KBr): 2250,1650,1600,1320,1280,858,800,740,69
5,680 cm ^-1 .Example 5 In the coexistence of 35 mg (0.60 mmol) of potassium fluoride and 1.8 mg (0.005 mmol) of allyl palladium chloride dimer, 53 mg (0.30 mmol) of 2-thienyl (ethyl) difluorosilane and 3-iodo were prepared by the same experimental procedure as in Example 1. Benzaldehyde
46 mg (0.20 mmol) was reacted to obtain 31 mg of 3-formylphenyl-2-thienyl ketone. Yield 72%. ¹ H-NMR (CDCl ₃ ): δ6.58-8.63 (m, 7H), 10.20 (S, 1
H). IR (KBr): 3100,2850,1700,1620,1410,1310,1200,1120,
1055,810,730,720 cm ^-1 . Example 6 In the coexistence of 35 mg (0.60 mmol) of potassium fluoride and 1.8 mg (0.005 mmol) of allyl palladium chloride dimer, 53 mg (0.30 mmol) of 2-thienyl (ethyl) difluorosilane and 3-iodo were prepared by the same experimental procedure as in Example 1. Quinoline 51 mg (0.
20 mmol) was reacted to obtain 37 mg of quinolin-3-yl-2-thienyl ketone. Yield 78%. ¹ H-NMR (CDCl ₃ ): δ7.18 (m, 1H), 7.50-8.05 (m, 5
H), 8.20 (m, 1H), 8.65 (m, 1H), 9.35 (m, 1H). IR (KBr): 3050,1630,1590,1410,1290,1250,1060,800,7
53 cm ^-1 . Example 7 In the presence of potassium fluoride 35 mg (0.60 mmol) and allyl palladium chloride dimer 1.8 mg (0.005 mmol), phenyl (ethyl) difluorosilane 52 mg (0.30 mm) as in Example 1.
ol) and methyl 4-iodobenzoate 52 mg (0.20 mmol)
Were reacted to obtain 29 mg of methyl 4-benzoylbenzoate.
Yield 61%. ¹ H-NMR (CDCl ₃ ): δ3.90 (S, 3H), 7.30-7.79 (m, 5
H), 7.84 (d, J = 8Hz, 2H), 8.15 (d, J = 8Hz, 2H). IR (KBr): 3000,2950,1710,1640,1435,1275,1100,770,7
10,690 cm ^-1 . Example 8 In the presence of potassium fluoride 19 mg (0.30 mmol) and nickel chloride bis (triphenylphosphine) 6.5 mg (0.01 mmol), 4-tolyl (ethyl) was prepared by the same experimental procedure as in Example 1.
Difluorosilane 56 mg (0.30 mmol) and 4-iodoacetophenone 50 mg (0.20 mmol) were reacted to obtain 4-acetyl-4′-methylbenzophenone 31 mg. Yield 63
%. The spectral data were in agreement with those obtained in Example 1.

Example 9 In the presence of 60 mg (0.90 mmol) of potassium fluoride and 1.8 mg (0.005 mmol) of allyl palladium chloride dimer, 5-tolyl (ethyl) dichlorofuran 66 was prepared by the same experimental procedure as in Example 1.
mg (0.30 mmol) and 4-iodoacetophenone 50 mg
(0.20 mmol) was reacted to obtain 21 mg of 4-acetyl-4'-methylbenzophenone. Yield 43%. The spectral data were in agreement with those obtained in Example 1.

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Claims (1)

[Claims] 1. A general formula Ar-SiR _m X _3-m [wherein, Ar represents a substituted or unsubstituted aromatic group or a heteroaromatic group, R represents an alkyl group or the above Ar group, X represents
Represents a halogen or an alkoxy group, and m represents any of 0, 1, 2, and 3. ] A silyl group-substituted aromatic compound represented by the general formula Y-Ar '(wherein Y represents a leaving group and Ar' represents a substituted or unsubstituted aromatic group or heteroaromatic group) Represented by the reaction of an aromatic compound in the presence of a Group VIII transition metal catalyst, carbon monoxide and a fluoride ion source, a general formula ArCOAr '(wherein Ar and Ar' have the same meanings as described above). The method for producing a diaryl ketone represented by