JPS5940815B2 - Kanjiyoukagobutsunoseizouhou - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a compound of the general formula [wherein R is phenyl which may have a lower alkyl group, a halogen atom or a trifluoromethyl group as a substituent], which is useful as an analgesic, anti-inflammatory, antipyretic agent, etc. A represents a carboxyl group or a carbamoyl group.

] This relates to a method for producing a cyclic compound represented by the following. More specifically, the present invention relates to a compound represented by the general formula and a compound represented by the general formula [wherein X represents a hexalogen atom].

R has the same meaning as above. ] is reacted with a compound represented by the general formula [wherein R has the same meaning as above].

] was obtained and subjected to a nitrification reaction to obtain a compound represented by the general formula [wherein R has the same meaning as above]. ] This is a method for producing a cyclic compound represented by the general formula (), which is characterized by obtaining a compound represented by the following and then hydrolyzing it.
In the above general formula, examples of the lower alkyl group as a substituent of the phenyl group represented by R include methyl, ethyl, propyl, JsO-propyl, butyl, JsO-butyl,
Straight chain or branched atoms having 1 to 4 carbon atoms such as Sec-butyl and tert-butyl are used, and examples of the halogen atoms include chlorine, bromine, and fluorine.

One or more substituents of the 7-enyl group may be the same or different and may be substituted at any position of the phenyl group.

The position of the group represented by R-0- is not particularly limited, but the 4-position is particularly desirable. In the general formula (V), chlorine atoms represented by X include chlorine, bromine, and iodine.

In addition, in the general formula (), the hydroxyl group is preferably in the form of its salt,
Examples of such salts include alkali metal salts (eg, sodium, potassium, and lithium salts), alkaline earth metal salts (eg, calcium, and barium salts), and the like. Hereinafter, the method of the present invention will be explained for each step.

First, compound () and compound (V) are reacted under Ullmann reaction conditions to obtain compound (). This reaction is a compound (
) It is preferable to react 1 to 5 mol of compound (V) per 1 mol. This reaction may be performed in the presence of a basic substance (eg, alkali hydroxide, alkali hydride, alkali carbonate, alkali hydrogen carbonate, alkali acetate, etc.) if desired. The reaction is usually carried out without a solvent or in the presence of a solvent. Examples of the solvent include pyridine, dimethylformamide, dimethylacetamide, dimethylsulfoxide, colicin, nitrobenzene, methanol, ethanol, and water. This reaction proceeds at a temperature ranging from room temperature to the boiling point of the solvent. In some cases, the reaction proceeds smoothly when a metal catalyst is used. Examples of the metal catalyst include copper powder, copper oxide, copper halide, and the like. Next, compound () is subjected to a nitrification reaction to obtain compound ().

In this glycation reaction, a method known per se for converting a ketone into a nitrile is used. Specifically, for example, a method in which a sulfonylmethylisonitrile compound is used as a nitrifying agent [Method (2)], a method in which a hydroxyl group obtained by reduction of a carbonyl group is converted into a nitrile group and then nitrified with a cyanide salt [Method (2)] g) l)], etc. In method (1) described in ±, the sulfonylmethylisonitrile compound has the general formula R1-SO2-CH2N, for example.
Examples include compounds represented by C() (wherein R'' represents an aryl, aralkyl or alkyl group).

The aryl group represented by R'' in the general formula () includes, for example, a lower alkyl group having 1 to 3 carbon atoms (e.g., methyl, ethyl, propyl), a halogen atom (e.g., chlorine , bromine, fluorine), carbon number 1-3
Examples include phenyl, naphthyl, and tolyl groups which may be substituted with an alkoxy group (eg, methoxy, ethoxy, propoxy), among which phenyl, p-tolyl, and the like are practically advantageous. Further, examples of the aralkyl group represented by k include benzyl and phenethyl groups, and examples of the alkyl group include lower alkyl having 1 to 4 carbon atoms, such as methyl, ethyl, propyl, IsO-propyl, butyl, IsO-butyl, Sec
Examples include butyl and tert-butyl groups. The reaction is carried out using 1 mol or more of compound () per 1 mol of compound (),
It is preferably carried out by reacting 1 to 1.5 moles. This reaction is advantageously carried out in the presence of a solvent and a base. Examples of solvents include ethers such as dimethoxyethane, diethoxyethane, tetrahydrofuran, and dioxane, such as methanol, ethanol,
Examples include lower alcohols such as t-butanol, and mixed solvents thereof. In the case of a mixed solvent, the mixing ratio is preferably in the range of 2 to 20 parts of the ether to 1 part of the alcohol, particularly preferably in the range of 5 to 10 parts. Examples of bases include methanol, ethanol,
Examples include metal alcoholades made of lower alcohols such as tert-butanol and alkali metals such as sodium and potassium. The reaction temperature is selected from the range of 0 to 100°C depending on the reactivity of the compound used and the type of solvent, base, etc. used if desired, but a range of 10 to 40°C is particularly preferred. Generally the reaction is 1
Completed in ~6 hours. In the above nitrilation method (11), any reduction method may be used as long as it generally reduces a carbonyl group to an alcohol, but practically, for example, sodium borohydride, sodium borohydride,
Methods using metal hydrides such as lithium aluminum hydride, palladium, nickel, platinum, iron, rhodium,
Examples include catalytic reduction using a metal catalyst such as iridium, reduction using an alkali metal such as sodium, lithium, or potassium and a hydrogen-donating solvent such as alcohol or liquid ammonia, and reduction using a metal complex such as rhodium or iridium. In the case of catalytic reduction, hydrogen is used under normal pressure or increased pressure, and there are no particular limitations on the hydrogen pressure. When using lithium aluminum hydride, use an anhydrous ether solvent (e.g., ethyl ether, propyl ether, isopropyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether), when using an alkali metal, use liquid ammonia, anhydrous Alcohols (e.g., methanol, ethanol, propanol), etc. are preferred as the solvent. In other cases, water, alcohols, ethers, etc. are used. There are no particular limitations on the reaction temperature and reaction time. Hydroxy forms include hydrogen halides (e.g., hydrogen chloride, hydrogen bromide, hydriodic acid), thionyl halides (e.g., thionyl chloride, thionyl bromide), and phosphorous halides (e.g., phosphorus pentachloride, phosphorus trichloride). , phosphorus tribromide), etc., to form a halide without a solvent or in the presence of a solvent.If a solvent is used, any solvent may be used as long as it is inert to the reaction.For example, Examples include benzene, toluene, xylene, hexane, chloroform, methylene chloride, etc.The reaction temperature varies depending on the reagent and solvent used, but it generally proceeds under cooling or heating, and there is no limit to the reaction temperature.The halogen thus obtained The compound can be reacted with a cyanide salt such as sodium, potassium, copper, silver, etc. to lead to a compound of the general formula ().The reaction is generally carried out without a catalyst or in the presence of a catalyst.As a catalyst, for example, Examples of quaternary ammonium ions include tetraalkylammonium consisting of an alkyl group having about 1 to 20 carbon atoms and optionally substituted with an aryl group, such as tetrabutylammonium, triethylhexane, etc. Examples include decyl ammonium and triethylbenzylammonium. Also, common halide ions include chlorine and bromine.
Instead of using cyanide and a catalyst, ammonium cyanide may be used. In this case, the ammonium ion mentioned above may be used as the ammonium ion. There are no particular limitations on the reaction temperature and time. As a solvent for reacting cyanide without a catalyst, for example, dimethyl sulfoxide, N
-N-dimethylformamide, hexamethylphosphoric triamide, alcohols (eg, methanol, ethanol, isopropanol), acetone, water, etc. are excellent. Further, when using ammonium cyanide or a catalyst, water is preferable as a solvent. Then the general formula obtained (
Compound (1) can be obtained by hydrolyzing the compound (1).

Advantageously, the hydrolysis is optionally carried out in the presence of a catalyst. Examples of the catalyst include hydrogen halides (e.g., hydrogen chloride, hydrogen bromide, hydrogen iodide), mineral acids such as sulfuric acid, phosphoric acid, and polyphosphoric acid; formic acid, acetic acid, paratoluenesulfonic acid, β-naphthalenesulfonic acid, etc. organic acids; Lewis acids such as boron trisulfide and titanium tetrachloride; hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide; hydroxides of alkaline earth metals such as calcium hydroxide and barium hydroxide from lower alcohols consisting of alkyl groups having 1 to 4 carbon atoms (e.g., methanol, ethanol, propanol, IsO-propanol, butanol, IsO-butanol, Sec-butanol, tert-butanol) and alkali metals such as sodium and potassium. Hydrogen peroxide: Peracids such as peracetic acid and perbenzoic acid are used. These catalysts may be used alone, or two or more may be used simultaneously. The reaction temperature may generally be under cooling, at room temperature, or under heating. Moreover, the reaction time is not particularly limited. In this reaction, a compound of general formula (1) in which A is carbamoyl is obtained, and under strong conditions, the carbamoyl group is further hydrolyzed to obtain a compound in which A is a free carboxyl group.

In this case, of course, after the amide, ie, the compound in which A is a carbamoyl group, is isolated, it may be further hydrolyzed to obtain a compound in which A is a free carboxyl group. For example, an amide is obtained when concentrated sulfuric acid, concentrated hydrogen chloride, etc. are used as a catalyst when cold, when polyphosphoric acid is used as a catalyst when hot, and when boron trifluoride is used at room temperature. Further, when hot sulfuric acid, alkali metal hydroxide, etc. are used, a compound in which A is a free carboxyl group can be obtained. In the target compound (1) thus obtained, A may be interconverted between a free carboxylic acid, an acid amide, and an ester using a method known per se, if desired.

To convert a free carboxylic acid into an acid amide derivative, for example, amidation is performed by reacting it with an amine, or amidation is performed by converting it into an acid chloride and then reacting it with an amine. For example, esterification may be performed by reacting with alcohol in the presence of an acid. An example of converting an acid amide derivative into an ester derivative is alcoholysis using an acid as a catalyst. To convert an ester derivative into a free carboxylic acid, for example, hydrolysis in the presence of an alkali or an acid can be used, and to convert an ester derivative into an acid amide derivative, for example, amidation by reacting with an amine can be used. Can be mentioned. General formula (1) obtained by the above method
The compounds can be purified by conventional separation means such as recrystallization, distillation, chromatography, etc.

Since the cyclic compound represented by the general formula () obtained by the method described above has an asymmetric carbon at the 1-position in the molecule, it can be divided into d-isomer and 1-isomer by a method known per se. can do.

That is, the racemic free acid is added to a suitable inert solvent such as chloroform, acetone, benzene, hexane, ether, methanol, ethanol, acetonitrile, water, etc. and reacted with an optically active base to form the resulting salt or amide. is separated into diastereoisomers (Djastereoisomers) based on their solubility differences, and then treated with an acid to isolate the optically active form of the free carboxylic acid derivative. Alternatively, an ester is prepared from a racemic free acid and a suitable optically active alcohol, and this ester is separated into diastereoisomers by a method known per se, such as recrystallization, distillation, or chromatography.
Next, the optically active free carboxylic acid can be isolated by hydrolyzing the ester in the presence of an acid or a base. Examples of optically active bases used here include quinine, brucine, cinchonidine, cinchonine, dehydroabiethylamine, hydroxyhydrindamine, tanthylamine, morpine, α-phenylethylamine, phenyloxynaphthylmethylamine, quinidine, and strychnine. These include basic amino acids such as amines, lysine, and arginine, and esters of amino acids. Examples of optically active alcohols include borneol, menthol, and 2-octanol. The compound of general formula (1) obtained by optical resolution as described above can be converted into an optically active derivative in its carboxyl group by a treatment method known per se as described above.
The compound represented by the general formula (1) obtained by the present invention has antipyretic, analgesic and antiinflammatory effects.

Therefore, compounds of general formula (1) are useful as antipyretics, analgesics and anti-inflammatory agents, and a daily adult dose of about 50
~2000 η can be administered orally, either neat or together with a pharmacologically acceptable inert carrier in a suitable dosage form such as tablets, capsules, granules, etc., or an adult daily dose of about 10 to 1000 m It can be administered parenterally together with a pharmacologically acceptable inert carrier in the form of an injection, ointment, suppository, or the like. The present invention will be explained in more detail with reference to Examples below.

Example 1 In 100 ml of dry pyridine, 157 parts of 4-human xyindan-1-one, 147 parts of potassium carbonate and 3 parts of potassium carbonate were added.
Add 17 bromobenzene and heat in a nitrogen stream.

When reflux started, 107 cupric oxide was added and the mixture was heated for 8 hours.
Continue stirring at partial reflux. Add 50 ml of benzene and hydrochloric acid (200 ml of concentrated hydrochloric acid + 500 m0 of water) to the reaction mixture. Remove insoluble matter by filtration. Separate the benzene layer and the aqueous layer, and extract the aqueous layer with benzene. Combine the benzene layers with water. Wash and dry. The solvent is distilled off under reduced pressure. The residue is purified by column chromatography (silica gel 3007, eluted with benzene) and crystallized from cyclohexane to give 4-phenoxyindan-1- Yield 42% Melting point 80.5-82.0°C Elemental analysis Cl5
Hl2O2 Calculated value C: 80.33, H: 5.39 Experimental value C: 80.49, H: 5.48 In the same manner as above, 4-phenoxylene was prepared from 4-hydroxyindan-1-one and iodobenzene. Ciindane-1-one is obtained.

Yield: 37% The melting point and various spectra of this product match those obtained above. 3.36 obtained in this way
4-phenoxyindan-1-one of y and p of 4.47
-Toluenesulfonylmethylisonitrile is added to 50 ml of dimethoxyethane and stirred at room temperature.

Next, a solution of sodium ethoxide made from 520 ml of sodium metal and ethanol dissolved in a mixed solvent consisting of 10 ml of ethanol and 35 ml of dimethoxyethane is added dropwise. After the addition is complete, stir at room temperature for 4 hours. Add ice and hydrochloric acid to make acidic, then extract with ether.
The extracted layer is washed with water and then dried with magnesium sulfate. The solvent is distilled off under reduced pressure. The residue is purified by column chromatography on silica gel (silica gel 3007, eluted with chloroform) to obtain 4-phenoxyindane-1-carbonitrile. Yield 46% Infrared absorption spectrum (neat) 2230c7rL-1: 4-phenoxyindane-1-carbonitrile with nitrile group absorption 1.67 was
1 of 60% sulfuric acid and refluxed for 2.5 hours in a nitrogen stream.

After cooling, add water and extract with ether. Next, the ether layer is extracted with a 5% aqueous potassium carbonate solution. The extracted layer is washed with ether and then acidified with hydrochloric acid. Extract the precipitate with chloroform. The extracted layer is washed with water and then dried with magnesium sulfate. The solvent is distilled off under reduced pressure. When the residue is crystallized from cyclohexane, 4-phenoxyindane-1-carboxylic acid is obtained as crystals with a melting point of 9798°C. Yield 70% Elemental analysis value Cl6Hl4O3 Calculated value C: 75.57H: 5.55 Experimental value C: 75.60H: 5.48 Example 2 In the same manner as Example 1, 4-hydroxyindan-1-
4-(m-chlorophenoxy)indan-1-one is obtained from one and m-chlorobromobenzene.

Yield 45% Melting point 116.5-118.0°C. The recrystallization solvent is a mixed solvent of hexane and cyclohexane. Elemental analysis value
Cl5HllO2Cl Calculated values C: 69.64, H: 4.29, Cl: 13.

71 Experimental values C: 69.57, H: 4.03, Cl: 13.
54 In the same manner as in Example 1, 4-(m-chlorophenoxy)indan-1-carbohydrate was prepared from the 4-(m-chlorophenoxy)indan-1-one obtained above and p-toluenesulfonylmethylisonitrile. Nitrile is obtained.

[Purify by silica gel column chromatography (elution with benzene). ] Yield 47% infrared absorption spectrum (
Neat) 2230CrIL-1, nitrile 4-(m-chlorophenoxy) in the same manner as in Example 1
From indane-1-carbonitrile and sulfuric acid, melting point 108
．． 4-(m-chlorophenoxy)indan-1-carboxylic acid is obtained as crystals at 5-109.5°C.

(Recrystallization solvent is cyclohexane) Yield 53% Elemental analysis values Cl6H,3O3Cl Calculated values C: 66.56, H: 4.54, Cl: 12.
28 Experimental values C: 66.60, H: 4.29, C1: 12.
12 Example 3 In the same manner as in Example 1, 4-hydroxyindan-1-
4-(p-chlorophenoxy)indan-1-one is obtained from p-chlorobromobenzene and p-chlorobromobenzene.

Yield 43% Melting point 60.0-61.0℃ (Recrystallization solvent is a mixed solvent of hexane and cyclohexane) Elemental analysis value Cl
5HllO2Cl calculated value C: 69.64, H: 4.29, C1: 13.
71 Experimental values C: 69.51, H: 4.32, Cl: 13.
38 In the same manner as in Example 1, 4-(p
4-(p-chlorophenoxy)indan-1-carbonitrile is obtained from -chlorophenoxy)indan-1-one and p-toluenesulfonylmethylisonitrile.

[Purify by silica gel column chromatography (eluted with chloroform). ]Yield 40% Infrared absorption spectrum (neat) 2230cIn-1: Absorption of nitrile group In the same manner as in Example 1, from the 4-(p-chlorophenoxy)indan-1-carbonitrile obtained above and sulfuric acid with a melting point of 133- 1
4-(p-chlorophenoxy)indan-11-carboxylic acid is obtained as crystals at 35°C.

[Recrystallization solvent is cyclohexane] Yield 41% Elemental analysis value Cl6Hl3O3Cl Calculated value C: 66.56, H: 4.54, C1: 12.
28 Experimental values C: 66.34, H: 4.61, Cl: 12.
69 Example 4 In the same manner as in Example 1, 4-hydroxyindan-1-
4(0-chlorophenoxy)indan-1-one is obtained from O-chlorobromobenzene and O-chlorobromobenzene.

Yield: 13.5%; melting point: 87.0-88.5°C; recrystallization solvent: pacyclohexane. Elemental analysis value Cl5HllO2Cl Calculated value C: 69.64, H: 4.29, Cl: 13.
71 Experimental values C: 69.37, H: 4.27, C1: 13.
65 Example 5 In the same manner as in Example 1, 4-hydroxyindan-1-
4-(m-methylphenoxy)indan-1-one is obtained from one and m-bromotoluene.

Melting point 115.5-116.5°C. The recrystallization solvent was cyclohexane. Yield 38% Elemental analysis value Cl6Hl4O2 Calculated value C: 80.64, H: 5.92 Experimental value C: 80.55, H: 5.96 In the same manner as in Example 1, the above-obtained 4-( 4-(m-Methylphenoxy)indan-1-carbonitrile is obtained as crystals with a melting point of 56.0-57.0°C from m-methylphenoxy)indan-1-one and p-toluenesulfonylmethylisonitrile.

[Purify by silica gel column chromatography (eluting with benzene). ] Yield 42% Elemental analysis value Cl7Hl
5ON calculated value C: 81.90sH: 6.06, N: 5
．． 62 experimental values C: 81.63, H: 5.84, N: 5
, 71 In the same manner as in Example 1, 4-(m-methylphenoxy)indan-1-carbonitrile was obtained as crystals with a melting point of 102.5-104.5°C.
-methylphenoxy)indan-1-carboxylic acid is obtained.

[Recrystallization solvent is cyclohexane] Yield 41% Elemental analysis value C17H1603 Calculated value C: 76,10, H: 6,01 Experimental value C: 76.12, H: 5.94 Example 6 Same as Example 1 The process provides 4-(p-methylphenoxy)indan-1-one from 4-hydroxyindan-1-one and p-bromotoluene.

Melting point 93.5-94.5°C. The recrystallization solvent was cyclohexane. Yield 28% Elemental analysis value C16H1402 Calculated value C: 80.64, H: 5.92 Experimental value C: 80.91. H: 5.72 In the same manner as in Example 1, 4-(p-methylphenoxy)indan-1-carbonitrile was obtained from 4-(p-methylphenoxy)indan-1-one and p-toluenesulfonylmethylisonitrile obtained above. is obtained.

Yield: 47% Infrared absorption spectrum (neat): 2250 cm-1: 2.0y of 4-(p-methylphenoxy)indan-1-carbonitrile was added to polyphosphoric acid with a nitrile group absorption of 507.
Continue heating on a 130°C oil bath for 5 hours while stirring.

After cooling, water is added and the precipitate is extracted with ethyl acetate. The extracted layer is washed with water and then dried. The residue obtained by distilling off the solvent under reduced pressure is purified by column chromatography (silica gel: 2007, eluted with a mixed solvent of benzene:ethyl acetate 10:3). When the obtained crude crystals are recrystallized from ethyl acetate, crystals with a melting point of 194-197°C are obtained.
4-(p-methylphenoxy)indan-1-carboxylic acid amide is obtained. Yield 48% Elemental analysis value C17H
170N Calculated value C: 76.38, H: 6.41. N:5.24
Experimental values C: 76.02, H: 6.22, N: 5.13
Add 1.57 g of 4-(p-methylphenoxy)indan-1-carboxylic acid amide to 100 ml of concentrated hydrochloric acid and reflux for 6 hours.

After cooling, add 50 ml of water and extract with ether.
After washing the ether layer with water, it is extracted with a 1% aqueous sodium hydroxide solution. The extracted layer is washed once with ether and acidified with hydrochloric acid. The precipitate is extracted with ether, and the extracted layer is washed with water and then dried. When the residue obtained by distilling off the solvent under reduced pressure is crystallized from a mixed solvent of cyclohexane-hexane, crystals with a melting point of 115-118.5°C are obtained.
-(p-methylphenoxy)indan-1-carboxylic acid is obtained. Yield 75% Elemental analysis value C17H1603
Calculated value C: 76.10, H: 6.01 Experimental value C: 76.03, H: 6,10 Example 7 In the same manner as in Example 1, 4-hydroxyindan-1-
1 and m-trifluoromethylbromobenzene to 4-
(m-trifluoromethylphenoxy)indan-1-
You can get on.

Melting point 102.5-104. The O'Co recrystallization solvent was cyclohexane. Yield 31% Elemental analysis value C,6H11F30
2 Calculated values C: 65,75, H: 3.79 Experimental values C: 65.77, H: 3.72 4-(mtrifluoromethylphenoxy) obtained above in the same manner as in Example 1 ) indan-1one and p-toluenesulfonylmethylisonitrile as an oil, 4
-(m-trifluoromethylphenoxy)indan-1
- carbonitrile is obtained.

[Purify by silica gel column chromatography (eluting with benzene). ] Yield 34% infrared absorption spectrum (
Neat) 2230C7rL-]: Nitrile In the same manner as in Example 1, from the 4-(mtrifluoromethylphenoxy)indan-1 carbonitrile obtained above as a crystal with a melting point of 78.0-79.5°C, 4-(m-
Trifluoromethylphenoxy)indan-1-carboxylic acid is obtained.

Yield 66% Elemental analysis value C17H1303F3 Calculated value C: 63.35, H: 4.06 Experimental value C: 63.21, H: 4.11 Example 8 In the same manner as Example 1, 6-hydroxyindan- 1-
6-phenoxyindan-1-one is obtained as crystals with a melting point of 53.0-54.5°C from 1-one and bromobenzene.

(Recrystallization solvent: cyclohexane) Yield: 26% Elemental analysis value: C15H1202 Calculated value: C: 80.33, H: 5.39 Experimental value: C: 80.14, H: 5.25 In the same manner as in Example 1, the above 6-phenoxyindane-1-carbonitrile is obtained from the 6-phenoxyindane-1-one obtained in step 1 and p-toluenesulfonylmethylisonitrile.

[Column chromatography (eluted with silica gel 3007, benzene monoethyl acetate (50:1))] Yield 47%
Infrared absorption spectrum (neat) 22300fn-1: Nitrile 6-phenoxyindane-1-carbonitrile obtained above and sulfuric acid in the same manner as in Example 1, melting point 73.0
6-phenoxyindane-1-carboxylic acid is obtained as crystals at -75.0°C.

[Recrystallization solvent: hexane-cyclohexane (1:1)]
Yield 46% Elemental analysis value Cl6Hl4O3 Calculated value C: 75.57, H: 5.55 Experimental value C: 75.35, H: 5.25 Reference example 1 10y of 4-phenoxyindan-1 in 200ml of methanol Dissolve 1-one and add 1.5y of sodium borohydride.

After stirring for 1 hour at room temperature, add a small amount of acetone.
The solvent was distilled off under reduced pressure, water was added to the residue, and the mixture was extracted with ethyl acetate. The extracted layer is washed with water and then dried. When the solvent was distilled off under reduced pressure, 4-phenoxyindan-1 was obtained as an oily substance.
-Oar is obtained. Yield 95% Elemental analysis value C, 5H
l4O2 Calculated value C:79.62, H:6.24 Experimental value C:79.44, H:6.13 Infrared absorption spectrum (neat): 3300Cr11-1: 4-phenoxyindan-1 with 7.88y hydroxyl group 1-all to 1
Dissolve in 50 ml of dichloromethane, add 4 ml of thionyl chloride and stir at room temperature for 1 hour.

The solvent and excess thionyl chloride are distilled off under reduced pressure to obtain 1-chloro-4-phenoxyindane as an oil. This material is dissolved in 50 ml of dimethylformamide without purification. This solution is added to 250 ml of dimethylformamide in which 1.72y of sodium cyanide has been dissolved and stirred for 6 hours in a nitrogen stream. Add to water in Step 21 and extract with benzene.

The extracted layer is washed with water and then dried. The residue obtained by distilling off the solvent under reduced pressure was subjected to column chromatography (silica gel 500
7. Elution with benzene) yields 4-phenoxyindane-1-carbonitrile. Yield: 43% The melting point and various spectra of this product match those of the compound obtained in Example 1. Reference Example 2 In the same manner as Reference Example 1, 4-(m-chlorophenoxy)
4-(m-chlorophenoxy)indan-1-ol is obtained from indan-1-one.

Yield 82% Melting point 66,0-68.5℃ (Recrystallization solvent is cyclohexane) Elemental analysis value Cl, Hl3O2Cl Calculated value C: 69.10, H: 5.02, Cl: 13,
60 Experimental values C: 68.83, H: 4.94, Cl: 13.
37 In the same manner as in Reference Example 1, 4-(m-chlorophenoxy)
4-(mchlorophenoxy)indan-1-carbonitrile is obtained from indan-1-ol.

Yield: 43% This product has various spectra that match those obtained in Example 2. Reference Example D In the same manner as in Reference Example 1, 4-(m-methylphenoxy)indan-1-ol is obtained from 4-(m-methylphenoxy)indan-1-one.

Yield 87% Melting point 46-48℃ Elemental analysis value Cl6Hl6
O2 Calculated value C: 79.97, H: 6.71 Experimental value C: 79.62, H: 6.57 In the same manner as in Reference Example 1, 4-(m-methylphenoxy)
4-(m-methylphenoxy)indan-1-carbonitrile is obtained from indan-1-ol.

Yield: 39% This product matches those obtained in Example 5 in melting point and various spectra. Reference Example 4 In the same manner as Reference Example 1, 4-(p-methylphenoxy)
4-(p-methylphenoxy)indan-1-ol is obtained from indan-1-one.

Yield 84% Melting point 68-7 "C elemental analysis value Cl6Hl6
O2 Calculated value C: 79.97, H: 6.71 Experimental value C: 79.59, H: 6.84 In the same manner as in Reference Example 1, 4-(p-methylphenoxy)
4-(p-methylphenoxy)indan-1-carbonitrile is obtained from indan-1-ol.

Yield 40% Infrared absorption spectrum (neat): 2250CT! L-1: Reference example of absorption of nitrile group 5
In the same manner as in Reference Example 1, 4-(m-trifluoromethylphenoxy)indan-1-ol is obtained from 4-(m-trifluoromethylphenoxy)indan-1-one.

Yield 89% Melting point 89-9'C (recrystallization solvent is cyclohexane). Elemental analysis value Cl6Hl3F3O2 calculated value C
:65.30. H: 4.45 Experimental value C: 65.32, H: 4.18 In the same manner as in Reference Example 1, 4-(m-trifluoromethylphenoxy)indan-1-ol was converted to 4-(m- Trifluoromethylphenoxy)indane-1-carbonitrile is obtained.

Claims (1)

[Claims] 1. A compound represented by the general formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ and the general formula R-X [In the formula, R represents a lower alkyl group, a halogen atom, or a trifluoromethyl group as a substituent] X represents a halogen atom. ] to obtain a compound represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [wherein R has the same meaning as above],
This is subjected to a nitrification reaction and the general formula ▲ mathematical formula, chemical formula,
There are tables, etc. ▼ [In the formula, R has the same meaning as above. ] There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by obtaining a compound represented by the following and then hydrolyzing it ▼ [In the formula, A represents a carboxyl group or a carbamoyl group. R has the same meaning as above. ] A method for producing a cyclic compound represented by