JPH06135883A - Production of aromatic acyl compound - Google Patents

Abstract

PURPOSE:To provide a method for reducing the amount of a Lewis acid to be used for solving problems such as the generation of a corrosive acidic gas in a Friedel-Crafts reaction industrially using a large amount of the Lewis acid. CONSTITUTION:When an aromatic compound is acylated with an acid halide or acid anhydride by their Friedel Crafts reaction, the Lewis acid and a catalytic amount of a silver salt are simultaneously used to reduce the amount of the Lewis acid to be used.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing an aromatic acyl compound, and more particularly to a method for acylating an aromatic compound with an acid halide, an acid anhydride, a mixed acid anhydride or an active ester. The present invention relates to a method for producing an aromatic acyl compound, which comprises using a catalytic amount of a silver salt together with a catalytic amount of a Lewis acid.

[0002]

BACKGROUND ART As a method for producing an aromatic acyl compound, a so-called Friedel-Crafts reaction in which an aromatic compound is reacted with an acid anhydride or an acid halide in the presence of a Lewis acid is well known. Is widely used industrially. (New Experimental Chemistry Course, 14 volumes, 799 pages and 806 pages, 197
(7 years, Maruzen). However, generally, at least 2 equivalents of Lewis acid are required when an acid anhydride is used as an acylating reagent, and at least 1 equivalent when an acid halide is used (New Experimental Chemistry Course, Volume 14, 801
Page and page 806, 1977, Maruzen).

[0003]

When a large amount of Lewis acid is industrially used, a corrosive acid gas is not added when the Lewis acid is added during the reaction or after the reaction. Occurs and this becomes a big problem. Therefore, development of a method for reducing the amount of Lewis acid used has been desired, but few reports have been made. For example, Hino et al. Used acetylation of toluene by heating iron (II) sulfate at high temperature as a catalyst (Chemistry Letters, 325).
Page, 1978). Yamaguchi et al. Are also studying the use of heteropolyacids and the like heated at high temperatures as a catalyst for acylation (Chemistry Letters, 1229 pages).
J., 1982). However, in these reports, it is necessary to activate the catalyst at a high temperature of several hundred degrees prior to the acylation reaction, which is not practical.

[0004]

The present inventors have found that when an aromatic compound is acylated with an acid halide or an acid anhydride, the presence of a catalytic amount of a Lewis acid and a catalytic amount of a silver salt causes a mild reaction. It was found that an aromatic acyl compound can be obtained in good yield under the conditions, and as a result of further detailed studies, the present invention has been completed.

That is, according to the present invention, when an aromatic compound and an acid halide, an acid anhydride, a mixed acid anhydride or an active ester are acylated by a Friedel-Crafts reaction, a catalytic amount of a Lewis acid is used. A method for producing an aromatic acyl compound, which comprises using a catalytic amount of a silver salt.

As the silver salt of the present invention, an inorganic silver salt or an organic acid silver salt can be used, and silver perchlorate, silver antimony hexafluoride, silver trifluoromethanesulfonate and the like are preferable. The amount used for the reaction is a catalytic amount, and the optimum amount can be selected from 1 mol% to 50 mol% with respect to the aromatic compound to be acylated, and the use of about 5 mol% to 30 mol% is preferable.

Other reaction conditions, that is, a reaction solvent,
As the conditions such as reaction temperature and reaction time, the conditions generally used in the Friedel-Crafts type acylation reaction can be applied. That is, the reaction solvent can be appropriately selected from halogen solvents such as carbon tetrachloride, chloroform, dichloromethane and dichloroethane, nitro solvents such as nitrobenzene and nitroethane, and solvents such as carbon disulfide. The reaction temperature can be selected from the temperature range from −80 ° C. to the boiling point of the solvent in consideration of the reaction time and the yield.

The Lewis acid used in the present invention is a free acid.
What is generally used in the Del-Crafts type acylation reaction can be used, for example, titanium,
It can be selected from halides such as zirconium, iron, copper, boron, aluminum, gallium, indium, silicon, germanium, tin or antimony. They are, for example, gallium trichloride, tin tetrachloride,
Boron trichloride, germanium tetrachloride, antimony pentachloride, iron trichloride, aluminum trichloride, tin tetrachloride, indium trichloride, boron tribromide, zinc tetrachloride, tin dichloride, copper dichloride or titanium tetrachloride etc. is there. The amount used for the reaction is a catalytic amount, and the optimum amount can be selected from 1 mol% to 50 mol% with respect to the aromatic compound to be acylated, and the use of about 5 mol% to 30 mol% is preferable.

As the aromatic compound to which the present invention is applicable, aromatic compounds generally used in the Friedel-Crafts type acylation reaction can be used. For example, pyrrole, furan and thiophene. , Heterocyclic aromatic compounds such as pyridine, indole, benzofuran, and benzothiophene, or aromatic compounds such as benzene, naphthalene, and anthracene.

Further, the aromatic compound applicable to the present invention may have various substituents, for example, the compound represented by the general formula (I)

[0011]

[Chemical 1]

(Wherein R 1, R 2 and R 3 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, an alkanecarboxamide group, an alkylamino group, a dialkylamino group or a hydroxy group. , Het is pyrrole, furan, thiophene,
Aromatic heterocycles such as pyridine, indole, benzofuran, benzothiophene or benzene, naphthalene,
An aromatic ring such as anthracene is shown. ) And the general formula (II)

[0013]

[Chemical 2]

(Wherein R 1 and R 2 are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, an alkanecarboxamide group, an alkylamino group, a dialkylamino group or a hydroxy group, and Het Represents a heterocyclic aromatic compound such as pyrrole, furan, thiophene, pyridine, indole, benzofuran and benzothiophene, or an aromatic compound such as benzene, naphthalene and anthracene, and Y represents C
H2, O, or S is shown, n is an integer of 1 to 4, and COX is an acid halide, an acid anhydride, a mixed acid anhydride, or an active ester. ) Is an aromatic alkanoic acid compound.

The general manufacturing method of the present invention will be illustrated below. The aromatic compound represented by the above general formula (I) and the general formula (III) RCOX (III) (In the formula, R is a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms. , Or an optionally substituted aromatic ring, and COX represents an acid halide, an acid anhydride, a mixed acid anhydride, or an active ester). Using a catalytic amount of a silver salt with an amount of Lewis acid, the general formula (IV)

[0016]

[Chemical 3] (In the formula, R represents a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms, or an aromatic ring which may be substituted, and R 1, R 2 and R 3 are the same or Differently, a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, an alkanecarboxamide group,
Het represents an alkylamino group, a dialkylamino group or a hydroxy group, and Het represents a heterocyclic aromatic compound such as pyrrole, furan, thiophene, pyridine, indole, benzofuran or benzothiophene, or an aromatic compound such as benzene, naphthalene or anthracene. )
An aromatic acyl compound represented by can be produced.

The present invention can also be applied to an intramolecular Friedel-Crafts type acylation reaction. For example, the general formula (II)

[0018]

[Chemical 4]

(Wherein R 1 and R 2 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, an alkanecarboxamide group, an alkylamino group, a dialkylamino group or a hydroxy group, and Het Represents an aromatic heterocycle such as pyrrole, furan, thiophene, pyridine, indole, benzofuran and benzothiophene, or an aromatic ring such as benzene, naphthalene and anthracene, and Y represents CH2, O,
Alternatively, it represents S, n represents an integer of 1 to 4, and COX
Represents an acid halide, an acid anhydride, a mixed acid anhydride or an active ester. ), An acid halide, an acid anhydride, a mixed acid anhydride or an active ester derivative of an aromatic alkanoic acid represented by the formula (1) is subjected to an intramolecular acylation reaction using a catalytic amount of a silver salt together with a catalytic amount of a Lewis acid, (V)

[0020]

[Chemical 5]

(Wherein R 1 and R 2 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, an alkanecarboxamide group, an alkylamino group, a dialkylamino group or a hydroxy group, and Het Represents a heterocyclic aromatic compound such as pyrrole, furan, thiophene, pyridine, indole, benzofuran and benzothiophene, or an aromatic compound such as benzene, naphthalene and anthracene, and Y represents C
H2, O, or S is shown, and n is an integer of 1 to 4. An aromatic acyl compound represented by

The halogen atom represented by R1, R2 and R3 is fluorine, chlorine, bromine, iodine or the like.
In addition, an alkyl group represented by R1, R2, and R3, an alkoxy group, an alkylthio group, an alkanecarboxamide group,
Examples of the alkyl contained in the monoalkylamino group and the dialkylamino group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl,
Isopentyl, hexyl, cyclohexyl, heptyl,
It means a linear, branched, or cyclic alkyl group having 1 to 10 carbon atoms such as cycloheptyl.

The linear, branched or cyclic alkyl group having 1 to 10 carbon atoms represented by R means methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and isopentyl. , Hexyl, cyclohexyl, heptyl, cycloheptyl, etc. 1
It means a linear, branched, or cyclic alkyl group consisting of 10 carbon atoms.

[0024]

In the conventional Friedel-Crafts type acylation reaction of an aromatic compound, 1 equivalent or more of Lewis acid is required with respect to the starting aromatic compound, but according to the present invention, 1/10 to 1 The reaction is possible in / 5 equivalents, and various problems such as generation of corrosive acid gas due to Lewis acid when industrially using a large amount of Lewis acid are solved, and it is a safe, aromatic compound freeder- Crafts-type acylation reaction became possible.

[0025]

The present invention will be described in more detail with reference to the following examples.

Example 1 Preparation of 1- (4-methoxyphenyl) -1-hexanone 261 mg of anhydrous tin tetrachloride and 207 mg of silver perchlorate were suspended in 10 ml of dry dichloromethane and stirred at room temperature for 10 minutes. Next, 1.08 g of methoxybenzene (anisole) was added with stirring under ice cooling. Further, 4.28 g of hexanoic anhydride (caproic anhydride) was dissolved in 10 ml of dry dichloromethane and added dropwise. Then, at room temperature, 20
Stir for hours. After completion of the reaction, the reaction mixture was poured into diluted hydrochloric acid-ice and the aqueous phase was extracted with chloroform. The organic phase was washed with dilute hydrochloric acid, water, aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography, and 1.75 g of 1-
(4-Methoxyphenyl) -1-hexanone (oil)
Got

Examples 2 to 12 Various Lewis acids (10 mol%) and silver perchlorate (10 to 2)
0 mol%) and the same reaction as in Example 1 was performed 1- (4
-Methoxyphenyl) -1-hexanone was obtained. The results are shown in Table 1.

[0028]

[Table 1]

Examples 13 to 14 Example 1 using 10 mol% of gallium trichloride (GaCl3) as the Lewis acid and 10 mol% of various silver salts as the silver salt.
Perform the same reaction as. 1- (4-methoxyphenyl)-
1-hexanone was obtained. The results are shown in Table 2.

[0030]

[Table 2]

Example 15 Preparation of 1- (3,4-dimethoxyphenyl) -1-pentanone 176 mg of gallium trichloride and 414 mg of silver perchlorate were suspended in 10 ml of dry dichloromethane and stirred at room temperature for 10 minutes. Next, 1.38 g of o-dimethoxybenzene was added with stirring under ice cooling. Furthermore, 3.72 g of pentanoic anhydride (valeric anhydride) was dissolved in 10 ml of dry dichloromethane and added dropwise. Then, it stirred at room temperature for 6 hours.
After completion of the reaction, the reaction mixture was poured into diluted hydrochloric acid-ice and the aqueous phase was extracted with chloroform. The organic phase was washed with dilute hydrochloric acid, water, aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 2.06 g of 1- (3,4-dimethoxyphenyl) -1-pentanone (oil).

Examples 16 to 36 Various aromatic compounds were reacted with various acylating reagents using 10 mol% of gallium trichloride and 10 to 20 mol% of silver perchlorate, and the same procedure as in Example 15 was performed. The reaction was carried out to obtain various aromatic acyl compounds. The results are shown in Tables 3 and 4.

[0033]

[Table 3]

[Table 4]

Example 37 Production of 4'-methoxyacetophenone 261 mg of anhydrous tin tetrachloride and 414 mg of silver perchlorate were suspended in 10 ml of dry dichloromethane and stirred at room temperature for 10 minutes. Next, 1.08 g of methoxybenzene (anisole) was added with stirring under ice cooling. Further, 1.58 g of acetic acid chloride was dissolved in 10 ml of dichloromethane and added dropwise. Then, it stirred at room temperature for 40 hours. After completion of the reaction, the reaction solution was poured into a mixture of dilute hydrochloric acid and ice, and the aqueous phase was extracted with chloroform. The organic phase is diluted hydrochloric acid, water, sodium bicarbonate water,
The extract was washed with water and saturated saline and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography. Obtained 0.98 g of 4'-methoxyacetophenone (oil).

Examples 38 to 47 Anisole was acylated with various acylating reagents in the same manner as in Example 37 using 10 mol% of anhydrous tin tetrachloride and 10 to 20 mol% of silver perchlorate. -Acyl acyl compound was obtained. The results are shown in Table 5.

[0036]

[Table 5]

Example 48 Preparation of 1 H -2,3-dihydronaphtho [2,1-b] thiopyran-1-one 261 mg of anhydrous tin tetrachloride and silver antimony hexafluoride (A)
gSbF6) 688 mg with dried dichloroethane 20 ml
And was stirred at room temperature for 10 minutes. Next, 3-
3-((2 obtained by a conventional method from 2.32 g of ((2-naphthyl) thio) propanoic acid and 1.8 g of thionyl chloride.
-Naphthyl) thio) propanoic acid chloride was dissolved in 10 ml of dry dichloroethane and added and refluxed for 3 hours. After completion of the reaction, the reaction solution was cooled, poured into a mixture of ice and dilute hydrochloric acid, and the aqueous phase was extracted with chloroform. The organic phase was washed with dilute hydrochloric acid, water, aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography, and recrystallized from ethyl acetate-n-hexane to give 1.83 g of 1 H- 2.
3-Dihydronaphtho [2,1-b] thiopyran-1-one was obtained as crystals. mp 66-68 ° C.

Example 49 176 mg of gallium trichloride and silver antimony hexafluoride 68
A reaction similar to that in Example 48 was carried out using 8 mg to obtain 91%.
With a yield of 1.95 g of 1 H -2,3-dihydronaphtho [2,1-b] thiopyran-1-one was obtained as crystals. mp 65-68 ° C.

Example 50 The same reaction as in Example 48 was repeated except that 176 mg of gallium trichloride was used.
And 414 mg of silver perchlorate were used and reacted at room temperature for 20 hours. 1.90 g of 1 H -2,3-dihydronaphtho [2,1-b] thiopyran-1-one was obtained as crystals with a yield of 89%. mp 66-68 ° C.

Example 51 Intramolecular acylation reaction was carried out under reflux for 5 hours in the same manner as in Example 48 using an acid chloride obtained from 1.64 g of 4-phenylbutanoic acid, and 1.17 g of 80% yield was obtained. α-Tetralone was obtained as an oil.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI technical display location C07D 335/08 // C07B 61/00 300

Claims (2)

[Claims] 1. A Friedel-Crafts type acylation reaction, wherein one or two silver salts selected from the group consisting of an inorganic silver salt and an organic acid silver salt are added to an aromatic acyl compound. Production method. 2. Addition of one or two silver salts selected from the group consisting of silver perchlorate, silver antimony hexafluoride and silver trifluoromethanesulfonate in the Friedel-Crafts acylation reaction. A method for producing an aromatic acyl compound, comprising: