JPS5927335B2 - Method for producing 1↓-substituted↓-2↓-aryl↓-3↓-formylindoles - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 1-monosubstituted-2-aryl-3-formylindoles, and more specifically, in which the 1-position of the indole ring is substituted with a carboxyalkyl group or a sulfoalkyl group. The present invention relates to a method for producing 2-aryl-3-formylindoles.

Many indole derivatives are important as amino acids, alkaloids, dyes, and plant hormones.

Among them, dyes containing a 1-monosubstituted-2-arylindole ring are extremely useful as spectral sensitizing dyes for direct positive silver halide photographic emulsions. For example, special public relations
31896, 48-24046, 47-9309,
As seen in Patent Application No. 47-9308 and other specifications, dyes containing an indole ring have a higher sensitization rate than conventionally known cyanine dyes, and have excellent other photographic properties. However, in the indole ring-containing dyes mentioned in the above specifications, the 1st position of the indole ring is a lower alkyl group, and there are no examples of an alkyl group substituted with a water-solubilizing group such as a carboxy group or a sulfo group. Not shown. In addition, although Japanese Patent Publication No. 47-20727 and other publications suggest dyes in which the 1st position of the indole ring is substituted with a carboxy group or a sulfo group, specific examples thereof and 11-substituted - No examples of synthesis of 2-aryl-3-formylindoles are disclosed.

Among conventionally known cyanine dyes, cyanine dyes having an alkyl group substituted with a carboxyl group or a sulfo group in their molecular structure have a higher sensitization rate than cyanine dyes that do not have such a water-solubilizing group, and Although it is known that color stains and the like in photographic images can be improved, no examples of this have been found with indole ring-containing dyes, due to the difficulty in producing the intermediate raw materials. The following methods have been known for producing compounds in which the 1-position of 2-aryl-3-formylindole is substituted with an alkyl group.

For example, a method in which indole derivatives are formylated with formamides in dichlorobenzene and an acidic condensing agent such as phosphorus oxychloride (for example, Ger6l4, 325; JC
hem. SOc. l959, 3388-3400; Mi
[Farshungslab・AgfaLeverk
useMunch3. 8899), a method of reacting 3-formyl-2-phenylindole with dimethyl sulfate in a 40% potassium hydroxide aqueous solution (J.
hem. 1O, 255-8), a method in which the former is reacted with concentrated sodium hydroxide in monochlorobenzene and dimethyl sulfate (US Pat. No. 3,012,040), and indoindrodimethine cyanine chloride is reacted with potassium permanganate in aqueous methanol. Method of oxidizing with Zh.Obsh
ch. Khim. 32, l9l2-22), a method of reacting 1-methyl-2-phenylindole with formamides and phosgene in tetrahydrofuran (Chem.
Ber. 98(1), 274-9), etc., but in all of them, the substituent at position 1 is a substituted alkyl group such as 2-cyanoethyl group, but all others are methyl group,
Limited to alkyl groups such as ethyl groups. This is because the above method cannot be used as is because it has a water solubilizing group such as a sulfoalkyl group in its structure. Among them, a method for formylating 1-monosubstituted-2-arylindoles and 2-aryl-
The method of acting an alkylating agent on 3-formylindoles seems to be applicable industrially, but if the substituent at the 1-position is a simple alkyl group without a water-solubilizing group, either the former or the latter Although it is possible to obtain a pure target product in a fairly high yield using this route or method, there are significant differences in workability, purity, and yield when the 1st position is an alkyl group substituted with a carboxy group or a sulfo group. be. When the former route is adopted, the carboxyalkylation or sulfoalkylation reaction of 2-arylindole hardly occurs with a sodium alkoxide catalyst in an alcohol.
However, although it reacts in the presence of sodium amide in liquid ammonia, it is only on a laboratory scale and there are problems with industrial scale production. There are reports that alkylation at the l-position of indoles can be obtained in high yield using a potassium hydroxide-dimethyl sulfoxide system, but in the case of 1-carboxyalkyl or sulfoalkyl-2-arylindoles, the dimethyl sulfoxide used as the solvent Due to the high solubility and solubility of indoles in polar solvents due to carboxyalkyl or sulfoalkyl groups, isolation and purification from dimethyl sulfoxide or aqueous dimethyl sulfoxide systems is extremely difficult, and naturally the yield is low. . This tendency is particularly remarkable in the case of 1-sulfoalkyl-2-arylindole. When the 1-carboxyalkyl or 1-sulfoalkyl-2-arylindoles thus obtained are subsequently formylated with phosphorus oxychloride in formamides, exactly the same difficulties are encountered during the post-reaction work-up. Even in the latter route, when carrying out carboxyalkyl or sulfoalkylation at the 1st position of the indole ring while retaining the formyl group in the molecular structure, difficulties similar to those described above can naturally be expected, but in reality, after the completion of the reaction, When concentrating an alkaline solution of aqueous formamides in the process, the formyl group is retained in the structure of the isolate without side reactions, and the target product is easily separated as a solid from the concentrate, resulting in a high yield. It was found that it was possible to obtain

Accordingly, an object of the present invention is to provide a method for producing novel 2-aryl-3-formylindoles substituted at the 1-position with a carboxyalkyl or sulfoalkyl group.

A further object of the present invention is to provide a novel method for producing 2-aryl-3-formylindoles in which the 1-position is substituted with a carboxyalkyl or sulfoalkyl group, with improved workability, yield, etc.

The above object of the present invention was achieved by the following manufacturing method.

That is, by reacting the 2-aryl-3-formylindoles represented by the general formula () with the compound represented by the general formula (l) or (5) in dimethyl sulfoxide in the presence of an alkali hydroxide, the general formula ( 1-carboxyalkyl or 1-sulfoalkyl-2-aryl-3-formylindoles represented by 1) could be obtained. General Formula (1) A in General Formula (1) represents a carboxy group or a sulfo group.

In addition, the indole ring and the phenyl group at the 2-position in general formulas (1) and () are, for example, an alkyl group (preferably a lower alkyl group such as methyl, ethyl, propyl, butyl)
, an alkoxy group (preferably a lower alkoxy group such as methoxy, ethoxy, propoxy, butoxy), a nitro group,
It may be substituted with at least one of halogens (eg, fluorine, chlorine, bromine, iodine) and the like. General formula (), (I
B in V) represents -CO- or -SO2-. In the general formula (1V), X represents halogen (preferably iodine), and M represents hydrogen or an alkali metal (eg, potassium, sodium). General formula (1), (l), (
n in IV) represents an integer of 1 to 4. Furthermore, the 2-aryl-3-formylindoles having a sulfoalkyl group produced according to the present invention are usually isolated in the form of alkali metal salts.

Although it is not impossible to obtain the free form in aqueous solution using a strongly acidic ion exchange resin, it is extremely difficult. An important feature of the present invention is that the 2-aryl-3-formylindoles represented by the general formula () and the 2-aryl-3-formylindoles represented by the general formula () or (5)
By reacting the compound represented by the formula (1) in dimethyl sulfoxide in the presence of an alkali hydroxide,
The purpose is to obtain indoles of the general formula (1) by formylating 2-arylindoles in which the 1st position is substituted with a carboxyalkyl group or a sulfoalkyl group.
It is distinguished from the method for obtaining indoles.

In the present invention, the reaction temperature does not need to be particularly high because the reaction proceeds easily, and a temperature range from 0°C to 50°C is sufficient.

The reaction time is determined depending on the reaction temperature, but is from 2 hours to 10 hours. The reaction is indoles 1 of the general formula ()
The compound of general formula () or (5) may be used in an equimolar amount, but the amount can be adjusted as necessary.

For example, when equimolar or more of the compound of general formula () or (5) is used, the end point of the reaction is measured by thin layer chromatography.
There is an advantage that the disappearance of indoles can be observed from the spectrum. Furthermore, when the general formula (1) or (5) is used in equal moles or less, the end point of the reaction cannot be determined by the thin layer chromatograph. After the reaction, if the reaction solution is poured into water, the excess indole of the general formula () will precipitate as a solid and can be removed by a filtration operation. In either method, there is no significant difference in yield depending on the type of alkali hydroxide (potassium, sodium) or molar ratio. The indoles of general formula () used in the present invention are described by Ger. 6l
4,325 Specification, R. C. BlumeH. G. Lin
dwall, J. Org. Chem. lO, 255~8
(1945), J. Wiley, Org-Synth-
Col. Ol. , 539-42.

The compound of general formula () can be obtained as a commercial product. Further, the compound of general formula (5) is partially available as a commercial product, and can also be obtained by treating the compound of general formula () with an alkali halide. Next, typical production examples of the compounds represented by the general formulas () and QV) used as raw materials in the method of the present invention will be shown as reference examples.

Reference Example 1: Typical Example of Compound of General Formula () 3 - 53 ml of phosphorus oxychloride was added dropwise to 158 ml of formyl-2-phenylindole dimethylformamide while stirring while maintaining the temperature at 10 to 15 C.

A solution of 50.79 2-phenylindole dissolved in 175 ml of dimethylformamide was added dropwise to this, and the mixture was heated to 35°C.
Stir at ~40°C for 1 hour. Pour the reaction solution into ice water,
The mixture was made alkaline with an aqueous sodium hydroxide solution. After heating on a hot water bath for several minutes and cooling on ice, the precipitated solid was filtered out and washed with water.
After washing with warm ethanol and drying, the melting point is 247.0.
Reference Example 2: Representative example of compound of general formula ([V) 3- Potassium iodopropane sulfonate A solution of potassium iodo 839 dissolved in 700 ml of methanol was added with 1. .3-Add propane sultone 619, 30
The mixture was heated to reflux for a minute.

After cooling on ice, the precipitated crystals were collected and washed with methanol. Then, after washing with acetone and drying, the melting point is 245℃ (decomposition).
A colorless crystalline powder 125f1 was obtained. The present invention will be explained in more detail below using Examples.

Example 1 Preparation of 3-formyl-2-phenyl-1-(3-sulfopropyl)indole potassium salt 85% potassium hydroxide (329%) was dissolved in dimethyl sulfoxide (5%).
3-formyl-2-phenylindole 449 and 1,3-pyamagunsultone 29θ were added to the solution dissolved in 0.00ml and stirred at room temperature for 2 hours.

The reaction solution was poured into water 21, made weakly acidic with acetic acid, and then concentrated under reduced pressure. 500 ml of ethanol was added to the concentrate and the precipitate was filtered out. When recrystallized with ethanol and dried, the melting point is 19.
64 g (yield: 84.3%) of white to pale yellow powder having a temperature of 5.0 to 198.0°C was obtained. Example 2 Separate method for preparing the compound of Example 1 In a solution of 17.99 85% potassium hydroxide dissolved in 230 ml of dimethyl sulfoxide, 50.19 ml of 3-formyl-2-phenylindole and potassium 3-iodophane pansulfonate were added. 97.79 g of salt was added and stirred at room temperature for 5 hours.

The reaction solution was concentrated under reduced pressure, ethanol 21 was added to the concentrate, and the precipitate was filtered out. After recrystallization with ethanol and drying, a white to pale yellow powder 809 (yield 92%) was obtained. Example 3 3-formyl-2-phenyl-1-(4-sulfobutyl)indole potassium salt 3-formyl-2-phenyl was added to a solution of 85% potassium hydroxide 169 dissolved in 400 ml of dimethyl sulfoxide.
55 g of formyl-2-phenylindole and 689 g of potassium 4-iodobutanesulfonate were added, and the mixture was stirred at room temperature for 4 hours.

The reaction solution was poured into 2.5 liters of water to remove the precipitate, the solution was made acidic with acetic acid, and then concentrated under reduced pressure. 50% ethanol to concentrate
0 ml was added, and the precipitate was collected by F. When recrystallized with ethanol and dried, 70.8 g of white powder with a melting point of 300°C or higher (
A yield of 72%) was obtained. Example 4 Production of 1-(2-carboxyethyl)-3-formyl-2-phenylindole 3-formyl-2-phenylindole 53 was added to a solution obtained by dissolving 15.8 g of 85% potassium hydroxide in dimethyl sulfoxide 600a. , 29 and β-propiolactone 16.2
9 was added and stirred at room temperature for 3 hours.

Claims (1)

[Claims] 1. A 2-aryl-3-formylindole represented by general formula (II) and a compound represented by general formula (III) or (IV) are mixed in dimethyl sulfoxide in the presence of an alkali hydroxide. The general formula ( I
) A method for producing 1-carboxyalkyl or 1-sulfoalkyl-2-aryl-3-formylindoles. General formula (I) ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ General formula (II) ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ General formula (III) ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ General formula (IV) X-(CH_2)_n-B-O-M (In the general formulas (I) and (II), A represents a carboxy group or a sulfo group.Also, even if the indole ring or the phenyl group at the 2-position is substituted, Good. In general formulas (III) and (IV), B is -C
Represents O- or -SO_2-. X represents halogen, and M represents hydrogen or an alkali metal. General formula (
n in I), (III), and (IV) represents an integer of 1 to 4. )2 The manufacturing method according to claim 1, wherein the compound of general formula (I) is ▲a mathematical formula, a chemical formula, a table, etc.▼. 3. The manufacturing method according to claim 1, wherein the compound of general formula (I) is ▲a mathematical formula, a chemical formula, a table, etc.▼. 4. The manufacturing method according to claim 1, wherein the compound of general formula (I) is ▲a mathematical formula, a chemical formula, a table, etc.▼.