JP2002047238A - Method for synthesizing aromatic-substituted alicyclic ketone, and new aromatic organic compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To develop a new method for synthesizing an aromatic-substituted alicyclic ketone compound capable of being used in wide variety of fields such as optical materials, heat insulating materials, organic conductors, biologically active materials, medicinal intermediates, functional organic materials, organic liquid crystal materials and the like. SOLUTION: This method for synthesizing an aromatic-substituted alicyclic ketone comprises processes for synthesizing an aromatic alkyl-substituted aromatic 1,3-dioxorane derivative by using a geminal-dialkoxyalkyl aromatic sulfone derivative and a cyclohexenone derivative or a polycyclic aromatic-substituted dihydrocarbonyl derivative as raw materials, converting into a carboxylic acid by oxidation reaction and further cyclizing the carboxylic acid with an acid. The new aromatic organic compound is obtained by using the above synthesizing method.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to the synthesis of aromatic alkyl-substituted 1,3-dioxolane derivatives using geminal-dialkoxyalkyl aromatic sulfone derivatives and cyclohexenone derivatives or polycyclic aromatic-substituted dihydrocarbonyl derivatives as raw materials. The present invention relates to a novel synthesis method for synthesizing an aromatic-substituted aliphatic cyclic ketone compound, which comprises a step of conversion to a carboxylic acid by an oxidation reaction and cyclization with an acid. Furthermore, the present invention relates to a novel organic compound obtained using the synthesis method.

[0002]

2. Description of the Related Art Alkyl-substituted aromatic compounds are important industrial raw materials as electronic materials such as liquid crystals and intermediates for pharmaceuticals. The most common method of making these compounds is
This is a method of alkylating a benzene ring with an alkyl halide by a Friedel-Crafts reaction. The Friedel-Crafts reaction is the most common reaction for obtaining an alkyl-substituted aromatic compound, but the regioselectivity of the Friedel-Crafts reaction is low, and it is difficult to control the position at which an alkyl group is introduced. Further, when a primary alkyl halide is reacted, a secondary alkyl group or a tertiary alkyl group is introduced by a transfer reaction, and a primary alkyl group cannot be introduced. In addition, it is difficult to control the number of alkyl groups to be introduced in the Friedel-Crafts reaction. The polyalkylation precedes the monoalkylation because the alkylated product is more reactive than the precursor.

[0003] Aromatization reactions of non-benzene ring compounds have also received attention. Dehydrogenation of cyclic alkanes or cyclic alkenes is the most common method, but this method requires severe conditions and the yield is not satisfactory. The trimerization of ketones is also an interesting reaction, but the yield is still low. For these classical approaches,
Many improvements have been made in recent years with advances in organometallic chemistry. Although the acetylene trimerization reaction is useful, it is not easy to control the regiochemistry in the intramolecular reaction.
For the purpose of constructing a benzene ring, cycloaddition of [4 + 2] is also widely used, and the reaction between cyclopentadienone and acetylene is the oldest known one. Recently, cycloolefins or furans have been cycloadded with olefins and then oxidized.

By reacting 1,3-dienes with quinone,
Oxidation of the cycloaddition also produces aromatic compounds. A number of protocols have been developed for intermolecular [4 + 2] cycloaddition by using α, β, γ, δ-unsaturated heterocumulenes. Furthermore, it has been reported that alkylenes controlled by regio are formed by the intermolecular reaction between vinyl allenes and acetylenes.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for preparing an aromatic alkyl-substituted 1,3 compound from a geminal-dialkoxyalkyl aromatic sulfone derivative and a cyclohexenone derivative or a polycyclic aromatic-substituted dihydrocarbonyl derivative.
To provide a novel synthesis method for synthesizing an aromatic-substituted aliphatic cyclic ketone compound, comprising a process of synthesizing a dioxolane derivative, converting it to a carboxylic acid by an oxidation reaction, and further cyclizing with an acid. Furthermore, it was difficult to obtain by the conventional method, obtained by using the synthesis method, to provide a novel organic compound,
It is an object of the present invention.

[0006]

We have previously disclosed a single in-reactor process for synthesizing dienes and acetylenes (A. Orita, Y. Yamashiti).
a, A. Toh, J .; Oreta, Angew. Che
m. 1997, 109, 804, Angew. Che
m. Int. Ed. Eng 1.997, 36, 77
9) (A. Orita, N. Yoshioka, J.O.
reta, Chem. Lett. 1997, 102
3). In these disclosures, it has been shown that aldol-type coupling of sulfones and aldehydes, followed by a double elimination reaction, produces diene or acetylene molecules in a single reactor.

[0007] From such previous findings, an attempt was made to use cyclohexenones as carbonyl substrates. The process of the present invention is characterized in that not only the regioselectivity of the alkyl group to be introduced is high, but also it can be carried out extremely easily in a single reactor. The outline of the reaction is shown in FIG.

[0008]

FIG. 2 shows a method for obtaining an aromatic compound substituted with an alkyl group or the like from a cyclohexenone derivative and an aromatic sulfone derivative. As shown in FIG. 2, the aromatic sulfone derivative (2) is converted to a basic organometallic such as butyllithium, a cyclohexenone derivative (1), an electrophile such as benzoyl chloride, and tert-butoxy, for example. By continuous treatment with a basic metal alkoxide such as potassium (5 equivalents)
Various substituted phenyl compounds of interest (3), including alkyl-substituted aromatic compounds, are produced in good yields in a single vessel.

As the aromatic sulfone derivative, not only various alkylphenylsulfone derivatives such as hexylphenylsulfone but also phenylsulfonealkyl-dioxolanes such as 2- [3- (phenylsulfonyl) propyl] -1,3-dioxolane are used. Derivatives can be used. For example, when 2- [3- (phenylsulfonyl) propyl] -1,3-dioxolane is used, various alkyl aromatic-substituted 1,3-dioxolane derivatives are produced. As the carbonyl compound, it is possible to use not only cyclohexenone derivatives but also polycyclic aromatic dihydrocarbonyl derivatives such as tetralone derivatives, dihydrobenzanthracene-one derivatives, and dihydrobenzopyrene-one derivatives. Thus, a substituted polycyclic aromatic compound having one additional aromatic ring is formed.

In the examples, butyllithium was used as the basic organic metal. However, the present invention is not limited to this, and various alkyl metals or basic organic metals can be used. Further, although benzoyl chloride was used as the electrophile in the examples, the invention is not limited thereto, and various acid halides, acid anhydrides, or phosphoric acid halides can be used. In the examples, potassium tert-butoxide was used as the basic metal alkoxide. However, the present invention is not limited to this, and various alkyl metals or basic organic metal alkoxides or basic organic metal amides can be used.

Table 1 shows the results obtained by summarizing the starting compounds, products and yields used in the examples described later. In addition to simple alkyl groups such as methyl, ethyl and n-hexyl, it is also possible to introduce acid-sensitive groups. In the reaction of the present invention, the primary alkyl group is completely regiocontrolled and is introduced into the aromatic ring, which has advantages over the Friedel-Crafts reaction.

[0012]

[Table 1]

Further, a method for synthesizing an aromatic-substituted aliphatic cyclic ketone compound was studied. These compounds are substances of current interest as new materials. The present inventors have synthesized an aromatic alkyl-substituted 1,3-dioxolane derivative having an acetal group using a geminal-dialkoxyalkyl aromatic sulfone derivative and a cyclohexenone derivative or a polycyclic aromatic substituted dihydrocarbonyl derivative. A method for synthesizing an aromatic-substituted aliphatic cyclic ketone compound has been developed which comprises a process of converting the product to a carboxylic acid by oxidizing reaction, removing the protection by the acetal group, and cyclizing under acidic conditions. FIG. 3 shows a method for synthesizing an alkyl-substituted aromatic compound having an acetal group. When the geminal-dialkoxyalkyl aromatic sulfone derivative (4) is reacted with the cyclohexenone derivative or the polycyclic aromatic dihydrocarbonyl derivative (1) in the presence of butyllithium, benzoyl chloride, and potassium tert-butoxy, the above-described reaction is obtained. Aromatization occurs by the same mechanism as described above, and an aromatic alkyl-substituted 1,3-dioxolane derivative (5) having an acetal group is produced. Table 2 shows the results obtained by summarizing the starting compounds, products, and yields used in Examples described later.

[0014]

[Table 2]

Further, an aromatic-substituted aliphatic cyclic ketone compound was synthesized from the added acetal group by the method shown in FIG. When the alkyl-substituted aromatic compound (5) having an acetal group is treated with an oxidizing agent such as "oxone" (potassium hydrogen peroxysulfate), deprotection and oxidation of the acetal group occur, and the compound (6) having a carboxylic acid ) Is generated. By reacting compound (6) with an oxidizing agent such as trifluoromethanesulfonic acid (TfOH), the desired aromatic-substituted aliphatic cyclic ketone compound (7) is produced in good yield. As understood from the reaction mechanism, the final product (7) is a compound having one more aromatic ring than the starting material (1). In the example, potassium hydrogen peroxysulfate was used as the oxidizing agent,
The invention is not limited thereto, and various oxidizing agents can be used. Further, although trifluoromethanesulfonic acid is used as an acid in the examples, the invention is not limited thereto, and various strong acids can be used. Table 3 shows the results in which the starting compounds, products, and yields used in Examples described later are summarized.

[0016]

[Table 3]

As described above, various aromatic derivatives substituted with an alkyl group or the like can be synthesized by this method using a cyclohexenone derivative or a polycyclic aromatic dihydrocarbonyl derivative as a raw material. The method has the feature that synthesis can be performed completely in a single reactor in a completely regio-controlled manner. Further, an aromatic-substituted aliphatic cyclic ketone compound can be synthesized by applying this method. Since the reaction of the present invention proceeds under basic conditions, it completely eliminates the disadvantages of the Friedel-Crafts reaction. A similar method has been used in the Reformazki reaction of α-tetralones, but involves dehydrogenation under harsh conditions, with moderate yields. Obviously, the double elimination of the present method makes it easier to form a carbon-carbon double bond. No special or harsh conditions are required in each step of the method. The reaction conditions of the present invention are mild and practical, so that the present method can be widely applied to the synthesis of aromatic compounds which have been difficult to synthesize until now. The aromatic compound synthesized by this method can be used in a wide range of fields such as optical materials, heat-resistant materials, organic conductors, physiologically active substances, pharmaceutical intermediates, functional organic materials, and organic liquid crystal materials.

[0018]

Example 1 (Compound 3a) To hexylphenylsulfone (271.6 mg, 1.2 mmol) was added 6 ml of tetrahydrofuran, and at -78 ° C, a hexane solution of butyllithium (1.6 M, 0.69 ml, 1.1 mmol) was added.
Was added. After stirring at −78 ° C. for 30 minutes, 2-cyclohexen-1-one (96.1 mg, 1.0 mmol)
Followed by benzoyl chloride (0.174 ml,
1.5 mmol) was added. The temperature was raised to room temperature and stirred for 3 hours. potassium tert-butoxide (562 mg, 5
mmol) and heated under reflux for 3 hours. After adding a saturated aqueous solution of ammonium chloride, the aqueous layer was extracted with diethyl ether and dried over sodium sulfate. The ether extract was concentrated under reduced pressure and isolated and purified by silica gel column chromatography to obtain hexylbenzene (75%).
%, 121.7 mg, 0.75 mmol, compound 3a)
was gotten. Hexylbenzene reference: Knickerbox
er, B .; M. Pesheck, C .; V. ; Scri
ven, L .; E. FIG. Davis, H .; T. , J .; Phys
s. Chem. 1979, 83, 1984-90.

[0019]

Example 2 (Compound 3b) In Example 1, 3-methyl-2-cyclohexen-1-one was used in place of 2-cyclohexen-1-one. 1-hexyl-3-methylbenzene (compound 3b) was 72% (12%).
6.9 mg). References for 1-hexyl-3-methylbenzene: Mam
edova, L .; Z. Lyutfalliev, A .;
G. FIG. Mutalim-Zade, S .; R. ; Mame
dova, Z .; A. Azerb. Kim. Zh. 198
4,24-6.

[0020]

Example 3 (Compound 3c) In Example 1, 3-ethyl-2-cyclohexen-1-one was used in place of 2-cyclohexen-1-one.
-Hexylbenzene (Compound 3c) was 69% (131.
3 mg). This substance is a new compound. Spectrum data of 1-ethyl-3-hexylbenzene: 1H NMR (CDCl3) δ 0.88 (t, J
= 6.9 Hz, 3H), 1.23 (t, J = 7.6H)
z, 3H), 1.26-1.38 (m, 4H), 1.5
6-1.64 (m, 2H), 2.58 (t, J = 7.9
Hz, 2H), 2.63 (q, J = 7.6 Hz, 2
H), 6.98-7.03 (m, 3H), 7.17-
7.21 (m, 1H).

[0021]

Example 4 (Compound 3d) In Example 1, 3,5-dimethyl-2-one was used in place of 2-cyclohexen-1-one.
When 1-cyclohexen-1-one was used, 1,3-dimethyl-5-hexylbenzene (compound 3d) was converted to 84
% (159.9 mg). This substance is a new compound. References for 1,3-dimethyl-5-hexylbenzene:
Truce, W.C. E. FIG. VanGemert, B .; B
rand, W.C. W. , J .; Org. Chem. 197
8, 43, 101-105.

[0022]

Example 5 (Compound 3e) Instead of 2-cyclohexen-1-one in Example 1, 3,6-dimethyl-2
When using -cyclohexen-1-one, 1,4-dimethyl-2-hexylbenzene (compound 3e) was converted to 79
% (159.9 mg). This substance is a new compound. Spectral data of 1,4-dimethyl-2-hexylbenzene: 1H NMR (CDCl3) δ 0.89
(T, J = 6.8 Hz, 3H), 1.26-1.44
(M, 6H), 1.50-1.59 (m, 2H), 2.
25 (s, 3H), 2.29 (s, 3H), 2.54
(T, J = 7.9 Hz, 2H), 6.90 (d, J =
7.6 Hz, 1H), 6.94 (s, 1H), 7.01
(D, J = 7.6 Hz, 1H).

[0023]

Example 6 (Compound 3g) When 6- (tert-butyldimethylsilyloxy) hexylphenylsulfone was used in Example 4 instead of hexylphenylsulfone, 1- (6-tert-butyldimethylsilyloxyhexyl) -3,5-dimethylbenzene (compound 3 g) was obtained in a yield of 72% (230.8 mg). This substance is a new compound. Spectral data of 1- (6-tert-butyldimethylsilyloxyhexyl) -3,5-dimethylbenzene: 1H NMR (CDCl3) [delta] 0.04 (s, 6)
H), 0.89 (s, 9H), 1.31-1.38
(M, 4H), 1.48-1.53 (m, 2H), 1.
55-1.62 (m, 2H), 2.29 (s, 6H),
2.52 (t, J = 7.6 Hz, 2H), 3.59
(T, J = 6.6 Hz, 2H), 6.80 (s, 2
H), 6.81 (s, 1H).

[0024]

Example 7 (Compound 3h) When crotylphenylsulfone was used in place of hexylphenylsulfone in Example 1, 1-butenylbenzene (compound 3h) was obtained.
Was obtained in a yield of 59% (78.0 mg). References for 1-butenylbenzene: Panek, E .;
J. Neff, B .; L. Chu, H .; ; Pane
k, M .; G. FIG. , J .; Am. Chem. Soc. 197
5,94,3996.

[0025]

Example 8 (Compound 3i) In Example 1, alpha-tetralone was used in place of 2-cyclohexen-1-one, and 1-hexylnaphthalene (compound 3
i) was obtained in a yield of 82% (174.1 mg). References for 1-hexylnaphthalene: Jaxa-Cha
miec, A .; Shah, V .; P. Kruse,
L. T. , J .; Am. Chem. Soc. Perkin
TransI 1989, 1705.

[0026]

Example 9 (Compound 3j) When 6-methoxy-1-tetralone was used in place of 2-cyclohexen-1-one in Example 1, 1-hexyl-6-methoxynaphthalene (Compound 3j) was 74% (179.4 mg)
In a yield of This substance is a new compound. Spectral data of 1-hexyl-6-methoxynaphthalene: 1H
NMR (CDCl3)? 0.89 (t, J = 6.9
Hz, 3H), 1.25-1.46 (m, 6H), 1.
68-1.77 (m, 2H), 3.02 (t, J = 7.
8Hz, 2H), 3.92 (s, 3H), 7.13-
7.19 (m, 3H), 7.35 (t, J = 7.2H)
z, 1H), 7.60 (d, J = 8.2 Hz, 1H),
7.95 (d, J = 8.8 Hz, 1H).

[0027]

Example 10 (Compound 3k) When methylphenylsulfone was used in Example 9 instead of hexylphenylsulfone, the yield of 6-methoxy-1-methylnaphthalene (Compound 3k) was 76% (130.9 mg). I got it. This substance is a new compound. Spectral data of 6-methoxy-1-methylnaphthalene: 1H NMR (CDCl3) δ 2.66 (s, 3
H), 3.93 (s, 3H), 7.13-7.20.
(M, 3H), 7.33 (t, J = 7.1 Hz, 1
H), 7.60 (d, J = 8.2 Hz, 1H), 7.9
0 (d, J = 9.1 Hz, 1H).

[0028]

Example 11 (Compound 31) When 6,7-dimethoxy-1-tetralone was used in Example 1 instead of 2-cyclohexen-1-one, 2,3 dimethoxy-5-hexylnaphthalene (Compound 31) was 79% (2L)
(15.2 mg). This substance is a new compound. Spectral data of 2,3-dimethoxy-5-hexylnaphthalene: 1H NMR (CDCl3) δ 0.90
(T, J = 7.0 Hz, 3H), 1.25 to 1.50
(M, 6H), 1.70-1.82 (m, 2H), 3.
00 (t, J = 7.7 Hz, 2H), 4.01 (s, 3
H), 4.02 (s, 3H), 7.14 (s, 1H),
7.19 (d, J = 7.2 Hz, 1H), 7.26 (d
d, J = 7.2, 8.2 Hz, 1H), 7.28 (s,
1H), 7.56 (d, J = 8.2 Hz, 1H).

[0029]

Example 12 (Compound 3m) When 1,4-dihydrobenzo [a] anthracene-1 (2H) -one was used in place of 2-cyclohexen-1-one in Example 1, 1-hexylbenzo [a] anthracene (Compound 3m) In a yield of 78% (243.8 mg). This substance is a new compound. Spectral data of 1-hexylbenzo [a] anthracene: 1H NMR (CDCl3) δ 0.95 (t,
J = 7.0 Hz, 3H), 1.38-1.51 (m, 4
H), 1.64-1.72 (m, 2H), 1.98-
2.11 (m, 2H), 3.53 (t, J = 7.8H)
z, 2H), 7.47-7.60 (m, 5H), 7.6
5-7.78 (m, 2H), 7.99-8.11 (m, 2H)
2H), 8.35 (s, 1H), 9.19 (s, 1
H).

[0030]

Example 13 (Compound 3n) In Example 1, 9,10 dihydrobenzo [a] pyrene-7 (8H) -one was used in place of 2-cyclohexen-1-one, and 1-hexylbenzo [a] pyrene (Compound 3n) Was obtained in a yield of 88% (296.1 mg). This substance is a new compound. Spectral data of 1-hexylbenzo [a] pyrene:
1H NMR (CDCl3) δ 0.92 (t, J =
7.1 Hz, 3H), 1.30-1.46 (m, 4
H), 1.50-1.61 (m, 2H), 1.87-
1.98 (m, 2H), 3.36 (t, J = 7.8H)
z, 2H), 7.62 (d, J = 7.0 Hz, 1H),
7.73 (dd, J = 8.5, 7.0 Hz, 1H),
7.91 (d, J = 9.1 Hz, 1H), 7.96
(T, J = 7.6 Hz, 1H), 8.02 (d, J =
9.1 Hz, 1H), 8.07 (d, J = 7.0 Hz,
1H), 8.21 (d, J = 7.6 Hz, 1H), 8.
29 (d, J = 9.1 Hz, 1H), 8.71 (s, 1
H), 8.92 (d, J = 8.5 Hz, 1H), 9.0
4 (d, J = 9.1 Hz, 1H).

[0031]

Example 14 (Compound 5a) When 2- [3- (phenylsulfonyl) propyl] -1,3-dioxolan was used in place of hexylphenylsulfone in Example 1, 2- (3-phenylpropyl)- 1,3-Dioxolane (compound 5a) was obtained in a yield of 92% (176.9 mg). This substance is a new compound. Spectral data of 2- (3-phenylpropyl) -1,3-dioxolan: 1H NMR (CDCl3) δ
1.68-1.80 (m, 4H), 2.64-2.68
(M, 2H), 3.80-3.98 (m, 4H), 4.
86-4.89 (m, 1H), 7.15-7.20
(M, 3H), 7.25-7.29 (m, 2H).

[0032]

Example 15 (Compound 5b) When 2- [3- (phenylsulfonyl) propyl] -1,3-dioxolan was used in place of hexylphenylsulfone in Example 2, 2- [3- (3-methyl Phenyl) propyl]
83% of 1, -1,3-dioxolane (compound 5b) (17
1.2 mg). This substance is a new compound. 2- [3- (3-methylphenyl) propyl] -1,3
-Dioxolane spectral data: 1H NMR (C
DCl3) [delta] 1.65-1.79 (m, 4H), 2.
32 (s, 3H), 2.59-2.64 (m, 2H),
3.81-3.98 (m, 4H), 4.83-4.89
(M, 1H), 6.95-7.02 (m, 3H), 7.
12-7.18 (m, 1H).

[0033]

Example 16 (Compound 5c) When 2- [3- (phenylsulfonyl) propyl] -1,3-dioxolan was used in place of hexylphenylsulfone in Example 4, 2- [3- (3,5 -Dimethylphenyl) propyl] -1,3-dioxolane (compound 5c) 83%
(182.8 mg) in yield. This substance is a new compound. 2- [3- (3,5-dimethylphenyl) propyl]-
Spectral data of 1,3-dioxolan: 1H NM
R (CDCl3)? 1.65-1.75 (m, 4
H), 2.28 (s, 6H), 2.55-2.60.
(M, 2H), 3.80-4.00 (m, 4H), 4.
85-4.88 (m, 1H), 6.80 (m, 2H),
6.81 (s, 1H).

[0034]

Example 17 (Compound 5d) When 2- [3- (phenylsulfonyl) propyl] -1,3-dioxolan was used in place of hexylphenylsulfone in Example 8, 2- [3- (1-naphthyl) was obtained. ) Propyl] -1,
55% (133.3) of 3-dioxolane (compound 5d)
mg). This substance is a new compound. Spectral data of 2- [3- (1-naphthyl) propyl] -1,3-dioxolan: 1H NMR (CDCl
3) δ 1.77-1.85 (m, 2H), 1.86-
1.92 (m, 2H), 3.10-3.15 (m, 2
H) 3.83-4.00 (m, 4H), 4.85-
4.92 (m, 1H), 7.33 (d, J = 6.7H)
z, 1H), 7.38 (t, J = 7.6 Hz, 1H),
7.44-7.53 (m, 2H), 7.70 (d, J =
7.9 Hz, 1 H), 7.84 (d, J = 7.9 Hz,
1H), 8.04 (d, J = 7.6 Hz, 1H).

[0035]

Example 18 (Compound 5e) When 2- [2- (phenylsulfonyl) ethyl] -1,3-dioxolan was used in place of hexylphenylsulfone in Example 1, 2- (2-phenylethyl)- 1,3-Dioxolane (compound 5e) was obtained in a yield of 78% (139.0 mg). This substance is a new compound. Spectral data of 2- (2-phenylethyl) -1,3-dioxolan: 1 H NMR (CDCl 3) δ
96-2.01 (m, 2H), 2.73-2.78
(M, 2H), 3.85-4.04 (m, 4H), 4.
88-4.91 (m, 1H), 7.17-7.23
(M, 3H), 7.26-7.31 (m, 2H).

[0036]

Example 19 (Compound 5f = Compound 3f) In Example 2, instead of hexylphenylsulfone, 2- [2-
When (phenylsulfonyl) ethyl] -1,3-dioxolane was used, 2- [2- (2-methylphenyl)
Ethyl] -1,3-dioxolane (compound 5f)
% (150.0 mg). This substance is a new compound. 2- [2- (2-methylphenyl) ethyl] -1,3-
Dioxolane spectral data: 1H NMR (CD
Cl3) [delta] 1.95-2.00 (m, 2H), 2.3
2 (s, 3H), 2.68-2.73 (m, 2H),
3.85-4.01 (m, 4H), 4.88-4.91
(M, 1H), 6.99-7.14 (m, 3H), 7.
15-7.19 (m, 1H).

[0037]

Example 20 (Compound 5g) When 2- [2- (phenylsulfonyl) ethyl] -1,3-dioxolan was used in place of hexylphenylsulfone in Example 4, 2- [2- (3,5 -Dimethylphenyl) ethyl] -1,3-dioxolane (compound 5g) at 67%
(138.2 mg) in yield. This substance is a new compound. 2- [2- (3,5-dimethylphenyl) ethyl]-
Spectral data of 1,3-dioxolan: 1H NM
R (CDCl3) [delta] 1.94-1.98 (m, 2
H), 2.29 (s, 6H), 2.65-2.70
(M, 2H), 3.85-4.02 (m, 4H), 4.
88-4.91 (m, 1H), 6.84 (s, 3H).

[0038]

Example 21 (Compound 5h) When 2- [2- (phenylsulfonyl) ethyl] -1,3-dioxolan was used in place of hexylphenylsulfone in Example 8, 2- [2- (1-naphthyl) was obtained. ) Ethyl] -1,3-
Dioxolane (Compound 5h) is 60% (137.0 m
g). This substance is a new compound. Spectrum data of 2- [2- (1-naphthyl) ethyl] -1,3-dioxolan: 1H NMR (CDCl
3) δ 2.09-2.15 (m, 2H), 3.19-
3.24 (m, 2H), 3.88-4.07 (m, 4
H), 4.99-5.01 (m, 1H), 7.35
(D, J = 6.5 Hz, 1H), 7.40 (t, J =
7.5 Hz, 1 H), 7.45-7.54 (m, 2
H), 7.72 (d, J = 8.0 Hz, 1H), 7.8
5 (d, J = 7.5 Hz, 1H), 8.07 (d, J =
8.0 Hz, 1H).

[0039]

Example 22 (Compound 5i) When 2- [4- (phenylsulfonyl) butyl] -1,3-dioxolan was used in place of hexylphenylsulfone in Example 1, 2- (4-phenylbutyl)- 1,3-Dioxolane (compound 5i) was obtained in a yield of 62% (127.9 mg). This substance is a new compound. Spectral data of 2- (4-phenylbutyl) -1,3-dioxolan: 1H NMR (CDCl 3) δ
44-1.51 (m, 2H), 1.63-1.73
(M, 4H), 2.60-2.65 (m, 2H), 3.
81-3.99 (m, 4H), 4.83-4.87
(M, 1H), 7.15-7.19 (m, 3H), 7.
25-7.29 (m, 2H).

[0040]

Example 23 (Compound 7a) 2-Compound obtained in Example 14
(672 mg, 3.5 mmol, compound 5a) in (3-phenylpropyl) -1,3-dioxolane in THF
To the solution (10 mL), add “Oxone” (6.45 g, 1
0.5 mmol) in water (10 mL) was added with stirring at 0 °. The mixture was stirred at room temperature for 12 hours and water / EtOAc was added. The organic layer was washed with brine, dried (Na ₂ SO _4). The residue obtained by evaporation was subjected to silica gel column chromatography (70:30 hexane / EtOAc) to give 4-phenylbutanoic acid (compound 6a) (564 mg,
98%). 4-phenylbutanoic acid (164 mg, 1 mm
ol) at 5 degrees with trifluoromethanesulfonic acid (1 m
L), followed by stirring at room temperature for 2 hours. After diluting the reaction solution by adding finely crushed ice, the aqueous layer was extracted with diethyl ether, and the combined organic layers were washed successively with an aqueous sodium hydrogen carbonate solution, water and brine. After dehydrating and drying over sodium sulfate and concentrating the ether extract under reduced pressure, the residue was isolated and purified by silica gel column chromatography to give 2,3,4-trihydronaphthalen-1-one (98%, 144 mg, 0.98 mmol, compound 7
a) was obtained. References for 2,3,4-trihydronaphthalen-1-one: Burnham, J. W .; Duncan, W .;
P; Eisenbraun, E .; J. Keen, G .;
W. Hamming, M .; C. , J .; Org. Che
m. 1974, 39, 1416-1420.

[0041]

Example 24 (Compound 7b) In Example 23, 2
Instead of-(3-phenylpropyl) -1,3-dioxolane, 2- [3- (3-methylphenyl) propyl] -1,3-dioxolane obtained in Example 15 (compound 5
When b) was used, 4- (3
(Methylphenyl) butanoic acid (Compound 6b) was obtained. 4
Cyclization reaction with trifluoromethanesulfonic acid using-(3-methylphenyl) butanoic acid gave 6
-Methyl-2,3,4-trihydronaphthalen-1-one (Compound 7b) was obtained in a yield of 97% (155.4 mg). Spectral data of 6-methyl-2,3,4-trihydronaphthalen-1-one: 1H NMR (CDCl3)
d 2.12 (tt, J = 6.6, 6.1 Hz, 2
H), 2.38 (s, 3H), 2.63 (t, 6.6H)
z, 2H), 2.92 (tJ = 6.1 Hz, 2H),
7.06 (s, 1H), 7.12 (d, J = 7.9H)
z, 1H), 7.94 (d, J = 7.9 Hz, 1H);
13C NMR (CDCl3) d 21.4, 23.
1, 29.3, 38.8, 126.9, 12
7.3, 128.9, 130.0, 143.8,
144.2, 197.7. References for 6-methyl-2,3,4-trihydronaphthalen-1-one: Burnham, J. et al. W. ; Dunc
an, W.S. P. Eisenbraun, E .; J. K
een, G .; W. Hamming, M .; C. , J .; O
rg. Chem. 1974, 39, 1416-142
0.

[0042]

Example 25 (Compound 7c) In Example 23, 2
Instead of-(3-phenylpropyl) -1,3-dioxolan, 2- [3- (3,5-dimethylphenyl) propyl] -1,3-dioxolan (compound 5c) obtained in Example 16 was used. However, 4- (3,5-dimethylphenyl) butanoic acid (Compound 6c)
I got When a cyclization reaction with trifluoromethanesulfonic acid was carried out using 4- (3,5-dimethylphenyl) butanoic acid, 6,8-dimethyl-2,3,4-trihydronaphthalen-1-one (compound 7c) was converted to 99. % (1
72.5 mg). Spectrum data of 6,8-dimethyl-2,3,4-trihydronaphthalen-1-one: 1H NMR (CDC
l3) d 2.06 (tt, J = 6.4, 6.1 Hz,
2H), 2.31 (s, 3H), 2.61 (s, 3
H), 2.62 (t, J = 6.4, 2H), 2.91
(T, J = 6.1 Hz, 2H), 6.90 (s, 1
H), 6.91 (s, 1H); 13C NMR (CDCl3) d 21.2, 22.
9, 23.1, 30.8, 40.8, 127.
2, 128.6, 131.2, 141.3, 1
42.6, 145.6, 199.6. References for 6,8-dimethyl-2,3,4-trihydronaphthalen-1-one: Burnham, J. et al. W. D
uncan, W.C. P. Eisenbraun, E .;
J. Keen, G .; W. Hamming, M .;
C. , J .; Org. Chem. 1974, 39, 141
6-1420.

[0043]

Example 26 (Compound 7d) In Example 23, 2
2- [3- (1-naphthyl) obtained in Example 17 instead of-(3-phenylpropyl) -1,3-dioxolane
When propyl] -1,3-dioxolane (compound 5d) was used, 4- (1-naphthyl) butanoic acid (compound 6d) was obtained by "Oxone (registered trademark)" treatment. Cyclization reaction with trifluoromethanesulfonic acid was performed using 4- (1-naphthyl) butanoic acid.
-Trihydrophenanthrene-1-one (compound 7d)
Was obtained in a yield of 99% (194.3 mg). Spectral data of 2,3,4-trihydrophenanthren-1-one: 1H NMR (CDCl3) d 2.3
1 (tt, J = 6.6, 6.1 Hz, 2H), 2.75
(Tt, J = 6.6 Hz, 2H), 3.40 (t, J =
6.1 Hz, 2H), 7.57-7.64 (m, 2
H), 7.76 (d, J = 8.5 Hz, 1H), 7.8
7 (dd, J = 7.3, 2.1 Hz, 1H), 8.12
(D, J = 8.5 Hz, 1H), 8.15 (dd, J =
7.3, 2.1 Hz, 1 H); 13 C NMR (CDCl 3) d 22.3, 25.
1, 38.0, 122.3, 124.4, 12
6.3, 126.5, 127.9, 128.3,
129.5, 131.0, 135.2, 14
2.5, 198.1. References for 2,3,4-trihydrophenanthren-1-one: Premasagar, V. et al. ; Palanis
wamy, V .; A. Eisenbraun, E .;
J. , J .; Org. Chem. 1981, 46, 297
4-2976.

[0044]

Example 27 (Compound 7f) In Example 23, 2
2- [2- (2-methylphenyl) ethyl] -1,3-dioxolan obtained in Example 19 instead of-(3-phenylpropyl) -1,3-dioxolan (compound 5f)
Using "oxone" treatment, 3-phenylpropionic acid (compound 6f) was obtained. A cyclization reaction with trifluoromethanesulfonic acid was performed using 3-phenylpropionic acid to give indan-1-one (compound 7f) in a yield of 99% (130.8 mg).

[0045]

Example 28 (Compound 7g) In Example 23, 2
Instead of-(3-phenylpropyl) -1,3-dioxolane, 2- [2- (3,5-dimethylphenyl) ethyl] -1,3-dioxolane (compound 5 g) obtained in Example 20 was used. However, 3- (3-methylphenyl) propanoic acid (compound 6g) was obtained by "Oxone" treatment. When a cyclization reaction with trifluoromethanesulfonic acid was performed using 3- (3-methylphenyl) propanoic acid, 5-methylindan-1-one (compound 7g ′) was obtained.
And 7-methylindan-1-one (compound 7g) (1: 1) was obtained in a yield of 99% (144.7 mg). 7-Methylindanone (7 g) spectral data: 1H NMR (CDCl3) d 2.6
4 (s, 3H), 2.65-2.68 (m, 2H),
3.09 (t, J = 5.9 Hz, 2H), 7.10
(D, J = 7.3 Hz, 1H), 7.28 (d, J =
7.6 Hz, 1 H), 7.43 (dd, J = 7.3,
7.6 Hz, 1H); 13C NMR (CDC13) d18.2, 25.
2, 36.6, 123.8, 128.9, 13
3.7, 134.3, 138.6, 155.7,
207.8. Reference for 7-Methylindanone (7 g): Budhram, R .; S. ; Palaniswam
y, V. A. Eisenbraun, E .; J. , J .;
Org. Chem. 1986, 51, 1402-140
6. Spectral data of 5-methyllindone (7g '): 1H NMR (CDCl3) d 2.45
(S, 3H), 2.67-2.70 (m, 2H), 3.
10 (t, J = 6.0 Hz, 2H), 7.19 (d, J
= 7.6 Hz, 1H), 7.28 (s, 1H), 7.6
6 (d, J = 7.6 Hz, 1H); 13C NMR (C
DC13) d 21.8, 25.4, 36.2,
123.3, 126.8, 128.3, 134.
6, 145.6, 155.5, 206.4. References for 5-Methylindanone (7g '): Budhram, R .; S. ; Palaniswam
y, V. A. Eisenbraun, E .; J. , J .;
Org. Chem. 1986, 51, 1402-140
6.

[0046]

Example 29 (Compound 7h) In Example 23, 2
2- [2- (1-naphthyl) obtained in Example 21 instead of-(3-phenylpropyl) -1,3-dioxolane
Using [ethyl] -1,3-dioxolane (compound 5h), 3- (3,5-dimethylphenyl) propanoic acid (compound 6h) was obtained by "oxone" treatment. When a cyclization reaction with trifluoromethanesulfonic acid was performed using 3- (3,5-dimethylphenyl) propanoic acid, 5,7-dimethylindan-1-one (compound 7) was obtained.
h) was obtained in a yield of 94% (150.6 mg). References for 5,7-dimethylindan-1-one: Ba
rtmann, W.C. Konz, E .; , Heteroc
cyclic. 1987, 24, 677.

[0047]

Example 30 (Compound 7i) In Example 23, 2
2- (4-phenylbutyl) obtained in Example 22 instead of-(3-phenylpropyl) -1,3-dioxolane
Using -1,3-dioxolane (compound 5i), 3- (1-naphthyl) propionic acid (compound 6i) was obtained by "oxone" treatment. 3- (1 naphthyl)
When cyclization reaction with trifluoromethanesulfonic acid was performed using propionic acid, 1,2-dihydrocyclopenta [1,2-a] naphthalen-3-one (compound 7
A mixture (2: 1) of i) and 2,3-dihydrophenalen-1-one (compound 7i ') was 90% (164.0 m
g). Reference of Benzo [e] indoneone (7i): Baddeley, G .; Holt, G; Maka
r, S. M. Ivinson, M .; G. FIG. , J .; Che
m. Soc. 1952, 3605-3607. 2,3-Dihydro-1-phenalenone
References to (7i '): Baddeley, G .; ; Ho
lt, G; Makar, S .; M. Ivinson,
M. G. FIG. , J .; Chem. Soc. 1952, 3605
-3607.

[0048]

Example 31 (Compound 7j) In the cyclization reaction of Example 23 with trifluoromethanesulfonic acid, 5-phenylpentanoic acid was used instead of 4-phenylbutanoic acid, and 2,3,4,5-tetrahydrobenzo [ a]
[7] Anulen-1-one (compound 7j) was 93% (1
49.0 milligrams). 1-Benzosuboneone (7j) spectral data: 1H NMR (CDCl3) d 1.78-
1.92 (m, 4H), 2.72-2.76 (m, 2
H), 2.94 (t, J = 6.4 Hz, 2H), 7.2
0 (d, J = 7.4 Hz, 1H), 7.31 (t, J =
7.6 Hz, 1H), 7.42 (td, J = 7.4,
1.4 Hz, 1 H), 7.72 (dd, J = 7.6,
13C NMR (CDCl3) d 20.7, 25.
1, 32.3, 40.7, 126.4, 12
8.4, 129.5, 132.0, 138.6,
141.1. References for 1-Benzosuboneone (7j):
Gilmore, R .; C, Jr. Horton, W .;
J. , J .; Am. Chem. Soc. 1951, 73,
1411-1414.

[0049]

According to the present invention, a novel process for synthesizing an aromatic-substituted aliphatic cyclic ketone compound from a geminal-dialkoxyalkyl aromatic sulfone derivative and a cyclohexenone derivative or a polycyclic aromatic-substituted dihydrocarbonyl derivative as raw materials. Was provided. Furthermore, novel aromatic organic compounds synthesized by the method of the present invention are provided.

[Brief description of the drawings]

FIG. 1 is a diagram showing an outline of a reaction mechanism of the present invention.

FIG. 2 is a diagram showing a reaction for obtaining an alkyl-substituted aromatic-substituted compound from a cyclohexenone derivative and an aromatic sulfone derivative.

FIG. 3 shows that a cyclohexenone derivative and a geminal dialkoxyalkyl aromatic sulfone derivative
FIG. 2 is a diagram showing a reaction for obtaining an alkyl-substituted aromatic compound having an acetal group.

FIG. 4 is a diagram showing a reaction for obtaining an aromatic-substituted aliphatic-substituted cyclic ketone compound from an alkyl-substituted aromatic compound having an acetal group.

Claims (4)

[Claims] [Claim 1] Adding a basic organic metal to the geminal-dialkoxyalkyl aromatic sulfone derivative (n is 1 to 5) of
Then, (Wherein R ₁ , R ₂ and R ₃ are an alkyl group having 1 to 10 carbon atoms or hydrogen), then an electrophile, and then a basic metal alkoxide, and reacted. By collecting the product obtained from the reaction solution, A phenylalkyl 1,3-dioxolane derivative (R
₁ , R ₂ and R ₃ are an alkyl group having 1 to 10 carbon atoms or hydrogen, and n is 1 to 5), and are formed by adding an oxidizing agent to the phenylalkyl 1,3-dioxolane derivative. Collecting a product and collecting a product obtained by adding an acid to the product. Wherein R ₁ , R ₂ and R ₃ are an alkyl group having 1 to 10 carbon atoms or hydrogen, n
Is a synthesis method of 1 to 5). (2) Adding a basic organic metal to the geminal-dialkoxyalkyl aromatic sulfone derivative (n is 1 to 5) of
Then, (R ₁ and R ₂ are an alkoxy group having 1 to 10 carbon atoms or hydrogen), an electrophile is added, and then a basic metal alkoxide is added. By collecting the resulting product, A naphthylalkyl 1,3-dioxolane derivative (R ₁
And R ₂ are an alkoxy group having 1 to 10 carbon atoms or hydrogen, n is 1 to 5), and a product obtained by adding an oxidizing agent to the naphthylalkyl 1,3-dioxolane derivative is collected. And collecting a product obtained by adding an acid to the product. Aromatic substituted aliphatic cyclic ketone compounds (R ₁ and R ₂
Is an alkoxy group having 1 to 10 carbon atoms or hydrogen, and n is 1 to 5). (3) A phenylalkyl-substituted 1,3-dioxolane derivative (R ₁ , R ₂ and R ₃ are an alkyl group having 1 to 10 carbon atoms or hydrogen, and n is 1 to 5). (4) A naphthylalkyl 1,3-dioxolane derivative (R ₁
And R ₂ are an alkoxy group having 1 to 10 carbon atoms or hydrogen, and n is 1 to 5).