JPH04182477A - Production of substituted 2-oxa-7-aminoindane derivative - Google Patents

Abstract

PURPOSE:To industrially obtain the title compound useful as an intermediate of germicide for agriculture and horticulture in good efficiency by reacting a carboxylic acid derivative with a lower alkyl Grignard reagent. CONSTITUTION:A carboxylic acid derivative expressed by formula I (R<2> is lower alkyl) is reacted with a lower alkyl Grignard reagent to provide the objective substituted-2-oxa-7-aminoindane expressed by formula II (R<3> is lower alkyl). The above-mentioned reaction is normally carried out by using the lower alkyl Grignard reagent such as a trialkylaluminum or alkylmagnesium halide at an amount about 3-10 times, preferably about 3-5 times (by mol) as much as that of the carboxylic acid derivative expressed by formula I in a solvent such as THF, toluene or dichloromethane.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a method for producing substituted 2-oxa-7-aminoindan derivatives. For more details, please refer to JP-A-2-131
This invention relates to a method for producing substituted 2-year-old Kisafu-aminoindan derivatives that can be useful intermediates in producing acid amide compounds, which are active ingredients of agricultural and horticultural fungicides, as described in specifications such as No. 481. be.

The substituted 2-year-old xaf-aminoindan derivatives which are the subject of the method of the present invention are disclosed in, for example, JP-A-2-131481.
It is useful as an intermediate because it can lead to an acid amide compound represented by the general formula CI), which is useful as an active ingredient of agricultural and horticultural fungicides, by the following two routes described in the above.

[In the formula, R2, R2 and R4 represent a lower alkyl group, R5 represents a lower alkyl group or a trifluoromethyl group, and R6 represents a lower alkyl group, a halogen atom or a hydrogen atom. [Prior art] Conventionally, methods for producing substituted 2-year-old xaf-aminoindan derivatives include, for example, Comp, rend, 2
31, 911 (1950), JP 2-131481
The method described in No. 1 is known.

[In the formula, R', R2 and R3 have the same meanings as above. ] That is, a lactone derivative is obtained by reducing a phthalic anhydride derivative in an alcoholic solvent such as methanol or ethanol or an acetic acid solvent in the presence of metallic zinc and hydrochloric acid. Furthermore, the lactone derivative is reacted with a lower alkyl Grignard reagent such as methylmagnesium iodide in an ether solvent such as diethyl ether or tetrahydrofuran,
Obtain diol form. Next, the diol is reacted with activated manganese dioxide to obtain a substituted 2-oxa-7-aminoindan derivative.

<Problems to be Solved by the Invention> However, in the above production method, there is a problem in processing the manganese residue generated in the reaction. In addition, when carried out industrially, the yield is low and the reaction operation is complicated.
It is difficult to say that it is necessarily sufficient.

<Means for Solving the Problems> In view of the above circumstances, the present inventors have made intensive studies regarding the method for producing substituted 2-oxer-7-aminoindan derivatives, and have found that the general formula [wherein R2 is lower Represents an alkyl group. ] By reacting the carboxylic acid derivative represented by the formula with a lower alkyl Grignard reagent, [wherein R2 represents the same meaning as above and R3 represents a lower alkyl group]. ] It was discovered that the substituted 2-year-old xaf-aminoindan derivative represented by the following can be produced industrially and efficiently, leading to the present invention.

The carboxylic acid derivative represented by the general formula (It) above is reacted with a lower alkyl Grignard reagent, and the general formula CI
The reaction to obtain the substituted 2-year-old xaf-aminoindan derivative represented by ) is usually carried out in a solvent, and the solvents used include, for example, ethers such as tetrahydrofuran, hydrocarbons such as toluene, dichloromethane, monochlorohensen, etc. and mixtures thereof.

The lower alkyl Grignard reagent used in the above reaction is preferably an organoaluminum compound such as an organoaluminum compound such as doria alkylaluminum, an organomagnesium compound such as alkylmagnesium halide, an organolithium compound such as alkyllithium, etc. Can be mentioned.

The amount of the reagent used in the above reaction is about 3 to about 10 times the amount of the lower alkyl Grignard reagent, preferably about 3 to about 5 times the amount of the carboxylic acid derivative represented by the general formula [■]. be.

The reaction temperature is usually in the range of about -10C to the boiling point of the solvent, preferably about 10C to about 80C, and the reaction time is usually 1 hour to about 24 hours.

After the reaction is completed, the desired general formula CI[I
) can be obtained.

Further, if necessary, it can be further purified by conventional methods such as recrystallization and chromatography.

The carboxylic acid derivative represented by formula (If) is described in, for example, the Journal of the American
an Chemical Society, 69.1
909 (1947), 3-nitrophthalic acid in an alcoholic solvent such as methanol or ethanol,
in the presence of catalytic amounts of palladium carphone and acetic anhydride;
It can be synthesized by reacting with hydrogen under heating.

Furthermore, 3-nitrophthalic acid is available from, for example, Organi.
It can be synthesized by reacting phthalic anhydride with nitric acid in the presence of an acid such as sulfuric acid according to the method described in C. 5 Synthesis, 7.74 (1927).

<Effects of the Invention> The present invention provides a method for producing a substituted 2-oxa-7-amine indane derivative represented by the general formula [DI] which is useful as an intermediate for an acid amide compound represented by the general formula CI) having bactericidal activity. Regarding the method, the desired product can be advantageously produced by the method of the present invention.

<Example> Next, the present invention will be explained in more detail with reference to production examples, but the present invention is not limited to the following production examples.

Production Example 1 2.00 g of 3-acetaminophthalic anhydride was added to 50-
was dissolved in cyclohexane, and a 1M hexane solution of trimethylaluminum was slowly added dropwise thereto at room temperature for 30 hours. After the dropwise addition, the temperature was raised to 50°C, and the mixture was reacted at the same temperature for 4 hours. After the reaction was completed, the reaction mixture was poured into diluted hydrochloric acid and extracted with dichlorometal. The obtained extract was concentrated under reduced pressure and purified by silica gel chromatography to obtain 0.87 g of the target 3,3-dimethyl-7-acetaminophthalide.

Yield 40.8% 'H-NMR (CDCI!3) δppm1.6 (6H
, s), 2.2 (3H, s), 7.0 (I H, d,
J = 8.0 Hz), 7.6 (IH, dd
, J = 8.0 city), 8.5 (IH, d, J
= 8.0 City), 9.7 (IH, bs) Comparative Production Example I Cotnpt, rend, 231.911 (195
According to the method described in 0), 3-acetaminophthalic anhydride and acetic anhydride were dissolved in acetic acid, and a catalytic amount of zinc powder was added thereto in the presence of hydrochloric acid, followed by vigorous shaking. After the reaction, zinc is removed by filtration and the filtrate is purified to obtain 4
-acetaminophthalide was obtained.

Yield: 32.0% Comparative Production Example 2 α, α-
Dimethyl-2-hydroxymethyl-3-acetaminobenzyl alcohol was produced. 7.5 g of 4-acetaminophthalide was dissolved in 120-tetrahydrofuran (
; After dissolving, 130 ml of a 3M ether solution of methylmagnesium iodide was slowly added dropwise while cooling with water. After the dropwise addition, the temperature was gradually raised to room temperature, and the mixture was stirred overnight for reaction.

After the reaction was completed, the reaction mixture was poured into saturated ammonium chloride water under water cooling, and extracted twice with ethyl acetate. After drying and concentrating the extract, the obtained oil was purified using silica gel column chromatography.
, 7.2 g of white crystals of α-dimethyl-2-hydroxymethyl-3-acetaminobenzyl alcohol were obtained.

Yield 84.5% m, p, 137.9 °C 'H-NMR (CDCffi,') δppm1.6 (6
H, S), 2.1 (3H, S), 3.7 (2H, bs)
, 5.0 (2H,s), 7.2~7.8 (3
H, rn), 8.7 (18, bs) Comparative Production Example 3 3,3- according to the method described in JP-A-2-131481
Dimethyl-7-acetaminophthalide was produced.

7.2 g of α,α-dimethyl-2-hydroxomethyl-3-acetaminobenzyl alcohol was added to 30 g of chloroform.
Dissolve in 0ml, add 28g of activated manganese dioxide,
The mixture was heated to reflux for an hour. After the reaction was completed, the reaction mixture was allowed to cool and then filtered through a glass filter lined with Celite, and the residue was washed with 100% chloroform. The filtrate and washing liquid were combined and concentrated, and the resulting oil was purified by silica gel column chromatography to obtain 4.4 g of the target 3,3-dimethyl-7-acetaminophthalite.

Yield 606% m, p, 124.1'C HNMR (CDCjl'*) δppm1.6 (6H,
s), 2.2 (3H, S) 7.0 (jH, d,
J = 8.0 Hz), 7.6 (L H, d d
, J = 8.0 Hz), 8.5 (IH, d, J =
8.0 city), 9.7 (IH, bs)

Claims (1)

[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R^2 represents a lower alkyl group. ] A general formula characterized by reacting a carboxylic acid derivative represented by the above with a lower alkyl Grignard reagent ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^2 represents the same meaning as above, R^3 represents a lower alkyl group. ] A method for producing a substituted 2-oxa-7-aminoindan.