JPH0368533A - Production of diaryl ketone - Google Patents

Abstract

PURPOSE:To advantageously obtain the title compound of intermediate for synthesizing medicine in simple operation by reacting a silyl group-substituted aromatic compound with an aromatic compound in the presence of a catalyst, carbon monoxide and fluoride ion source using the silyl group-substituted aro matic compound and aromatic compound as raw materials. CONSTITUTION:A silyl group-substituted aromatic compound [e.g. 3-fluorophenyl (methyl)difluorosilane] expressed by formula I (Ar is aromatic group or heteroaromatic group; R is alkyl or the above-mentioned Ar group; X is halogen or alkoxy; m is 0 or 1-3) and used as a raw material is reacted with an aro matic compound [e.g. 4-iodine anisol) expressed by formula II (Y is eliminating group; Ar' is aromatic group or heteroaromatic group) and used as a raw mate rial in the presence of a catalyst (e.g. palladium benzalacetone complex) of the group VIII metal, carbon monoxide and fluoride ion source to provide the compound expressed by formula III. As the fluoride ion, potassium fluoride, etc., is used at a catalytic amount.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention is based on the general formula (1) % formula % (1) (where Ar and Ar' are substituted or unsubstituted aromatic groups or heteroaromatic groups). This invention relates to a method for producing a diarylketone represented by

According to the method of the present invention, pharmaceuticals ["Pharmaceutical Synthesis Manual W Volumes 1-4. CMC (198B)]" and agricultural chemicals ["Manual for the Production of New Pesticide Active Materials" Volumes 1-3. CMC (1989)]. A variety of diaryl ketones can be synthesized that are useful as synthetic intermediates.

In addition, polyfunctional diaryl ketones useful as highly selective oxidizing agents for steroids and the like can be efficiently synthesized (ChecSoc, Rev., 1.553 (1972)).
3 Furthermore, various diaryl ketones, which are industrially important as photopolymerization initiators and dye sensitizers, can be synthesized [“Applications of New and Fully Functional Polymers” CMC (19
88)).

[Prior art]

Conventionally, methods for synthesizing diarylketones include (1) the Fr1edel-Crafts reaction in which an aromatic hydrocarbon and an aromatic carbon oxide are reacted in the presence of dealluminium chloride;
Fr1edel-Crafts and Re1ate
d Reactions Vol III, Chap.
31. Intersclense, New Work (
1964); “Pr1edel-Crafts Che
+wistry'Wlley-1interscien
ce.

New York (1973), A Method for Condensing Aromatic Hydrocarbons to Carbon Tetrachloridec″Organic 5y
thesis' Co11゜Vol, 1.95(1
948)), ■Fr1es rearrangement reaction C″Fr1edel-Craf heating aromatic carboxylic acid ester
tsand Re1ated Reaction”
Vol, III, Chap 33゜Interscale
nce, New York (1964)), ■Condensation reaction of aromatic magnesium and cadmium compounds with aromatic compounds ("Organic Functional G
roup Preparation Vol I IC
hap 8. Academic, Nen York (1
983)), ■In the presence of a transition metal catalyst and carbon monoxide,
Method of reacting aromatic tin compounds and aromatic halides (Chem, Abstr, 95.114980m
) are disclosed.

[Problem to be solved by the invention]

Among these methods, methods ① and ② limit the substrates that can be used, and have low reaction selectivity;
method is difficult to synthesize asymmetric diaryl ketones. Furthermore, since the method (2) uses an active organometallic compound, protection is required when using a substrate with a functional group. In method (2), the substrates that can be used are significantly limited.

As described above, all of 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 to solve the problem]

The present inventors investigated an industrially easy method for producing a diaryl ketone having a functional group by eliminating such drawbacks, and found that - Formula (II) Ar-5IR-Xs - (IT
) (In the formula, Ar represents a substituted or unsubstituted aromatic group or heteroaromatic group, R represents an alkyl group or the above-mentioned Ar group, X represents a halogen or an alkoxy group, and the fineness is 0.1.
2.3) and the general formula (I[I)Y-Ar.
An aromatic compound represented by (I [I) (wherein Ar' represents a substituted or unsubstituted aromatic group or a heteroaromatic group, and Y represents a leaving group) is a group IV transition metal. catalyst,
By reacting in the coexistence of carbon oxide and fluoride ion sources, - Formula (1) % Formula % (1) (wherein Ar and Ar' represent the same meanings as above)
The present invention was completed by discovering that a diarylketone represented by the following formula could be obtained.

The silyl group-substituted aromatic compound represented by formula (fr), which is the raw material of the present invention, can be prepared by the following methods:
, 841 (1979)) ■ A method of reacting disilane with an aryl halide in the presence of a palladium catalyst (J, Or
ganomet, Chem, -128,409 (19
77)), and those with 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,
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) difluorosilane, phenyl (methyl) difluorosilane, phenyl (trimethyl) silane, phenyl (trifluoro) silane, phenyl (trichloro) silane, phenyl (
methyl)dichlorosilane, phenyl(triethyl)silane, l-naphthyl(trimethyl)silane, 1-naphthyl(ethyl)difluorosilane, 2-naphthyl(ethyl)silane
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)jethoxysilane, 2
-thienyl(methyl)dimethoxysilane and 2-pyridyl(ethyl)jethoxysilane.

The other raw material, the aromatic compound represented by formula (I[l) above, is an industrially easily available compound, and it
Examples including groups include 4-iodoanisole, 4-iodoethoxybenzene, 4-ethoxyphenyltrifluoroacetate, 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, (2-10 lophenyl) dimethyl phosphate, phenyl diethyl phosphate, 3-iodophenylacetic acid, ethyl 3-iodophenylacetate, 3-iodobenzyl acetate, vinegar #4-iodo Benzyl, a23-furomobenzyl acetate, 4-bromobenzyl acetate, 1-naphthyl (
methyl) sulfide, l-naphthyl (phenyl) sulfide, phenyl triflate, l-benzyl triflate, phenyl mezilad, phenyl (methyl) sulfide, l-benzyl (methyl) sulfide, 1-benzyl mezilad, 2-benzyl triflate, 4 - tolyl mezilad, 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-acetoxybromohenzene, 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, l-iodonaphthalene, 2-iodonaphthalene, etc. are used. be able to.

An essential condition for the present invention is that it be carried out in the presence of a fluoride ion source. As a fluoride ion source, tris(diethylamino)sulfonium difluorotrimethylsilicate, (TASF), tris(dimethylamino)sulfonium difluorotrimethylsilicate, tris(dimethylamino)sulfonium bifluoride, tetrabutylammonium fluoride, Onium fluoride salts such as benzyltrimethylammonium fluoride and penzyltriethylammonium fluoride, metal fluorides such as cesium fluoride, rubidium fluoride, and potassium fluoride can be used. The amount used can range from a catalytic amount to an excess amount relative to the silyl group-substituted aromatic compound, but is 0.8 to 2.0
It is preferable to use moles.

Examples of the metal catalyst used include Pd(0)II forms such as palladium tetrakis(triphenylphosphine), palladium benzalacetone complex, palladium dibenzalacetone chloroform complex, and allyl palladium 21 chloride.
body, palladium chloride bis(triphenylphosphine),
Pd(II) 11 bodies such as phenylpalladium bis(triphenylphosphine) iodide, benzylpalladium bis(triphenylphosphine) chloride, Nl(0) such as tetrakis(triphenylphosphine)nickel, nickel bis(triphenylphosphine) chloride N1 such as
(II) Pt(0) complexes such as II-form and tetrakis(triphenylphosphine)platinum can be used. The amount used may be a so-called catalytic amount.

An essential condition for the present invention is that it be carried out in the presence of carbon monoxide. Although the reaction can be carried out at a carbon monoxide pressure of 1.0 to 50 atm, a pressure of 1.0 to 3.0 atm is preferable for ease of operation.

The present invention is preferably carried out in a solvent, and in particular, carried out in an aprotic polar solvent is preferable from the viewpoint of reaction efficiency. -dimethylperhydropyrimidine 2-one, hexamethylphosphate triad, tetrahydrofuran, acetonitrile, N,N-
Dimethylimidazolidinone (DMI) can be used alone or in combination. The reaction is carried out at 50°C to 20°C.
It can be carried out in the range of 0℃, but it is easy to operate at 50~
120°C is desirable.

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

Example 1 ■ In a carbon monoxide atmosphere at 1 atm, 1.8 mg (0,005 mmol) of allyl palladium chloride dimer, 50 ut (0,20 mmol +) of 4-iodoacetophenone, and 19 av (0,33 mmol) of potassium fluoride l)
Add 4-tolyl(ethyl)Schiff JLz orosilane 56w (0.30 mmol I) to the DMI (1 ml) R solution and stir at 100°C for 3 hours. The reaction solution was subjected to mucochromatography (silica gel, hexane:ethyl acetate-10:
1) to remove the solvent.

The obtained crude product was further subjected to column chromatography (
4-acetyl-4'-methylbenzophenone 4-acetyl-4'-methylbenzophenone
I got 3 ■. Yield 91%.

■-NMR (CDCIs): δ2.45 (S, 3
11), 2゜63(S, 31()7.28(d, J-7
, 5Hz, 211), 7.70(d, J=7.5Hz,
2H) 7.80 (d, J = 8.011z, 211), 8
．． 04(d, J-8,0Hz, II).

rR(R11r) :1(i90.1645.1605
．． 1290, 1265, 930, 860°830.76
0 Rho Example 2 Following the same experimental procedure as in Example 1, potassium fluoride 35
(0,60 mmol) and allyl palladium chloride 1.8 w (0,005 mmol), 3-methoxyphenyl (propyl) difluorosilane 65 w (
0,30mmo I) and 3-iodobenzaldehyde 46+w (0,20mmo I) were reacted to form 3-
Formyl-3'-methoxybenzophenone 38a+r was obtained. Yield 80%.

'H-NMII (CDC11): δ3.92 (S
, 3B), 7.04-7.80 (an, 511), 8
．． 00-8.73 (m, 3H), 10.08 (S,
l1l).

IR (neat): 3100.2850.2750,
1700.1660, 1290°1245, 1040.
800,740 country-1 Example 3 1260.1035.780,745c*-'Example 4 St([!t)h Potassium fluoride 35■ (0,60 mm ol) es.

and allyl palladium chloride dimer 1.8■ (0,005m
3-methoxyphenyl(ethyl)difluorosilane 65w (0
, 30 mmol) and 1-iodonaphthalene 51w (
0.20 mmo +) was reacted to obtain 35 qr of 3-methoxyphenyl l-naphthyl ketone. Yield 67%.

'H-NMR (COCl): δ3.80 (S, 3t
l), 7.05-7.77 (m.

8! l), 7.80-8.25 (m, 3H) IR (ne
at) :3100,2950.166'0,1590
．． 1585,1280゜Potassium fluoride 35■ (0,6
Phenyl(ethyl)difluorosilane 5 was prepared using the same experimental procedure as in Example 1 in the coexistence of 0 mm o l ) and 1.8 mmol of allyl palladium chloride dimer (0,005 mmol).
2 g (0.30 mmol) and 46 .mu. of 4-iodoacetophenone (0.20 mmol I) were reacted to obtain 25 .mu. of 4-cyanobenzophenone. Yield 60%.

'H-NMR (CDCIs): δ7.20-8.
00 (m, 9H).

IR (KBr): 2250, 1650, 1600, 1
320.1280.858800740.695.68
0cm-' IR (KBr): 3100.2850.1700,16
20.1410.1310°1200.1120,10
55,810,730,720 cm-'Example 6 Potassium fluoride 35* (0,60 mm +) and allyl palladium chloride 1.8 cm (0,005 mm
2-thienyl(ethyl)difluorosilane 53■ (0.30mmol) in the same experimental procedure as in Example 1.
I) and 3-iodobenzaldehyde 46m (0
. Yield 72%.

H4MR (CDCIs): δ6.58-8.
63 (m, 7H), 10.20 (S, IH).

35 g (0,60 mmol) of potassium fluoride and 1.8 ■ (0,005 mmol) of allyl palladium chloride dimer
2-thienyl(ethyl)difluorosilane 53■ (0.30mmol) in the same experimental procedure as in Example 1.
l) and 3-yo)'quinoline 51w (0,20m
mol) was reacted to form K/IJ 73-yl-2-
Thienyl ketone 37μ was obtained. Yield 78%.

'H-NMR (CDCh): δ7.1B (Sono, I
H), 7.50-8.05 (m.

5B), 8.20 (Peng, 1M), 8.65 (m, LH)
, 9.35 (Otori, III).

[R (Br): 3050, 1630, 1590, 14
10.1290,1250゜1060.800,753
cm-' 5H), 7.84 (d, J-8Hz, 2H), 8.15
(d, J-8Hz, 2H).

/ IR (KBr): 3000.2950,171
0,1640,1435,1275°1100770.
710.690 cm-'Example 7 Example 8 St([!t)F.

35 sir (0,60 mmol) of potassium rifonide and 1,8 ■ sir (0,005 sir) of allyl palladium chloride dimer
phenyl(ethyl)difluorosilane (0.30 mmol) and methyl 4-iodobenzoate (52w (0.20 mmol)) in the same manner as in Example 1.
I) was reacted to obtain methyl 4-benzoylbenzoate 29 Akebono. Yield 61%.

'41-NMR (CnC1s): δ3.90 (S
, 3H), 7.30-7.79 (s.

7) Potassium chloride 19w (0,30mmo I) and nickel chloride bis(triphenylphosphine) 6.5w
4-Tolyl(ethyl)difluorosilane 56* in the same experimental procedure as in Example 1 in the presence of (0, Olmmo +)
(0,30mmo I) and 50 mg of 4-iodoacetophenone (0,2Qmmo I) were reacted, and 4
-Acetyl-4'-methylbenzophenone (31 parts) was obtained. The yield was 63%, consistent with that obtained by spectrum analysis.

The temperature was the same as that obtained in Example 1.

fruit Execution example ■

Claims (1)

[Claims] (1) General formula Ar-SiR_mX_3_-_n [In the formula, Ar represents a substituted or unsubstituted aromatic group or heteroaromatic group, R represents an alkyl group or the above Ar group, and X represents a halogen or alkoxy group. represents, m is 0, 1,
Represents either 2 or 3. ] and the general formula Y-Ar' (where Y represents a leaving group and Ar' represents a substituted or unsubstituted aromatic group or heteroaromatic group). of the general formula ArCOAr' (wherein Ar and Ar' have the same meanings as above). A method for producing a diaryl ketone represented by