CA1327583C - Substituted carboxylic acid derivatives, processes for preparing the same and agricultural or horticultural fungicides containing the same - Google Patents

Abstract

ABSTRACT
SUBSTITUTED CARBOXYLIC ACID DERIVATIVES, PROCESSES
FOR PREPARING THE SAME AND AGRICULTURAL OR
HORTICULTURAL FUNGICIDES CONTAINING THE SAME

A substituted carboxylic acid derivative which is fungicidally active is provided. The compound has the formula:

wherein R1 stands for a methyl or ethyl group, A stands for

Description

~27~

SUBSTITUTED CARBOXYLIC ACID DERIVATIVES PROCESSES
.
FOR PREPARING THE SAME AND AGRICULTURAL OR
HORTICULTURAL FUNGICIDES CONTAINING THE SAME

The present invention relates to substituted carboxylic acid derivatives, processes for preparing the same and agricultural or horticultur~l fungicides contain-ing the same as an active ingredient.

Fungicidal activity of some carboxylic acid derivatives is reported in e.g~, Japanese patent Kokai Nos. 52-87168, 58-96069 and 60-34949, US 4134987, G.A, Whites: "Pesticide ~iochemistry and Physiology 14, 26 (1980), J.L~ Huppatz: Aust. J. Chem~ 36, 135 (1983), B. Janks: Pestic. Sci.~ 2, 43, 1971, DEOS 2611601, Chem.
Abst. 70, 87799j (S. African 67 06, 681 Uniroyal Inc.), G.A. White et al.: "Pesticide Biochemistry and Physiology 5, 380-395, 1975 and M. Shell et al.: Phytopathology 60, 1164-1169, 1970. However, chemicals have been demandea which have higher fungicidal activity, since those known compounds are not satisfactory in activity.

After extensive research on compounds having high fungicidal activ~ty has been made, the present inventors find substituted carboxylic acid derivatives thereinafter referred to as the present compound) having the formula:
/ \ / 3 O F~ -C'~ C
Il 1 ~ ~CH (I) wherein Rl stands for a methyl or ethyl group;
A stands ~or - ., .i :.: .
-i : :

- 2 ~ 7 ~ ~ ~

~ 2 ~ 7/ ~7- i H3C R3 ~ R5 R2 stands for a methyl, ethyl or trifluoromethyl group;
R3 st.ands for a methyl group or a halogen or hydrogen atom; ~.4 stands for a fluorine or hydrogen atom; P~5 stands for a methyl, nitro, or trifluoromethyl group or a halogen atom; 2 stands for a =CH- group or an N atom;
R6 stands for a methyl, ethyl or trifluoromethyl group;
and R7 stands for an amino, methyl group or a chlorine atom.
According to the present invention, processes for preparing the present compound and agricultural or horticultural fungicides containing the present compound as an active ingredient are provided, too.
The present compound has preventive, curative and systemic controlling effects on various plant microbes, especially on plant diseases caused by microbes belonging to Basidiomycetes and gives almost no adverse influence to environment, The following are plant diseases on which the present compound has an excellent controlling effect;
Rhizoctonia solani and Rhizoctonia oryzae, R. solani III B
on rice plant; P'uccinia striiformis, P. 'gr'am'inis, -P. recondita, P. hordei, TY~hula incarnata, T. ishikariensis, Ustila~o tritici and U. nuda on wheat and barley;
Rh.izoctonia solani and Corticium rolfsii on various crops;
-Rhizoctonia solani on potato and beet; Gymnosporangium haraeanum on pear; Venturia inaequalis on apple;
Rhizoctonia solani, Corticium rolfsii, Uromyces trifolii : - ... .

:
,, , , ~ 3 - ~32~8~

and Typhula incarnata, T. ishikariensis on pasture and lawn.

Preferred compound among the present ones from a view point of fungicidal activity is a substituted carboxylic acid derivative having the formula:

/ \ /CH3 ~2 O Rl-CH C

3 (I~) wherein Rl, R2 and R3 are the same as those defined above, more preferred is c,ne having the formula:

R /
~ 8 OH r-~E: / C / 3 R~

wherein R8 stands for a methYl or trifluoromethyl ~roup and Rg stands for a halogen atom, and the most preferred ones are / O.
ÇH3 O H3C-CH \C / 3 I ~ C NH ~ \ CH3 H3C-N ~
Cl ' ~3~7~

CF3 H3C-C C.\ 3 ¦ / r C NH
H3C-N ~
Cl and o N CH3 O H3C ~ / \ / CH3 H3C ~ r \ CH3 Method for preparing the present compound will be explained in detail below.

[Method (A1]
Among the present compounds, a substituted carboxylic acid derivative havinq the formula:

/ \ / CH3 O R -CH C
~ C NH ~ CH3 (I) wherein A and Rl have the same meanings as those defined above, is prepared by allowing a substituted carboxylic acid having the formula:

A-COOH (II) wherein A has the same meaning as that defined above, or its reactive derivative to react with a substituted "' ' ' ~;

: ' ' , ' ' _ 5 _ ~3~7~$~

4-amino-2-oxaindan having the formula:

/ \ / 3 R1 - C~l \ CH (III) 2 ~
wherein R1 has the same meaning as that defined above.

The reaction is l~sually condu~ted in the~
presence of solvent which is not always necessary.
The solvents are, for example, hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as chlorobenzene, methylene chloride, chloroform and carbon tetrachloride, ethers such as diisopropyl ether, tetrahydrofuran and dioxane, ketones such as acetone and methyl ethyl ketone, esters such as ethyl acetate, nitriles such as acetonitrile, dimethylsulfoxide, dimethylformamide, water, etc., prefera~ly tetrahydrofuran.

Amounts of the reagents used in said reaction are 0.4-1.5 equivalents, preferably 0.5-l.l equivalents of the substituted caxboxylic acid represented by the formula (II) or reactive derivative t~ereof per equlvalent of the substituted 4~amino-2-oxaindan represented by the formula (III).

The reaction is carried out at optional temperature from the freezing point to the boiling point of the solvent, preferably from 0C to the boiling point of the solvent.

The substituted carboxylic acid represented by the formula (II) or reactive derivative thereof includes the corresponding carboxylic acids, acid anhydrides, acid chlorides, acid bromides, carboxylic esters, etc.

.

~' . . , , ;: ' - 6 ~ 7~

The reaction may be conducted in the presence of a reaction assistant depending on the substituted carboxylic acids represented by the formula (II) or reactive derivatives thereof. The reaction assistant is, for example t 1- (3-dimeth~laminopropyl)-3-ethylcarbodiimide-methiodide and dicyclohexylcarbodiimide when carboxylic acid is used, sodium hydride, sodium methylate, sodium ethylate~ etc. when carboxylic ester is used, and sodium hydroxide, potassium hydroxide, triethylamine, N-methylmorpholine, pyridine etc., when acid halide or acid anhydride is used. The reaction assistant is usually used in an amount of from a catalytic amount to 2 equivalents, preferably 0.95-1.1 equivalents.

After the reaction is over, the reaction assistant or reaction products thereof are removed by filtration or washing with water. The solvent was removed by distillatlon to give the desired substituted carboxylic acid derivatives of the formula (I). If necessary, the product i5 further subjected to ch~omatography, recrystallization, etc. in order to purify the same.

[Method (B)]
Among the present compounds, a substituted carboxylic acid derivative having the formula:

R O / \
N / 6 ll 1 ~ \CH
~ ,~ C -- NH ~ V ) Rlo wherein Rl and R6 are the same as those defined above and 35 Rlo stands for an amino or methyl group is prepared by allowing a substituted 4-amino-2-oxaindan _ 7 _ ~3~7~

derivative having the formula: O
/ \ ~ CH3 R~-CH ~ C
R6-COCHCONH ~ (V) Cl wherein Rl and R6 are the same as those defined above, to react with a thioamide derivative having the formula:
S

j~
R1o~C~NH (VI) wherein Rlo is the same as that defined above.

The reaction is usually conducted in the presence of a solvent which is not always necessary. Examples of the solvent are hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as chlorobenzene, ethers such as diisopropyl ether, tetrahydrofuran and dioxane, esters such as ethyl acetate, alcohols such as methanol and ethanol, dimethylsulfoxide, dimethylformamide and water.

Amounts of the reagents are not critical but usually 0.5-10 equivalents~ preferably 1-3 equivalents of the thioamide derivative having the formula (VI) per equivalent of the substituted 4 amino-2-oxaindan derivative having the formula (V).

The reaction is conducted at a temperature of from the freezing point of the solvent to the boiling point thereof, preferably from 0C to the boiling point of the solvent.

The reaction may be conducted in the presence of a base as a reaction assistant. The base is, for :}
. ~ , ~ , . .
, ~
., . ,., : .. . :

- 8 - ~7~

example, ammonia water, amines such as triethylamine and N-methylmorpholine, and inorganic ~ases such as potassium carbonate and sodium carbonateO

After the reaction is over~ the reaction assistant or reaction products thereof are removed by filtration or washing with water, and then the filtrate is subjected to distillation to remove the solvent until the desired substituted carboxylic acid derivative having the formula (IV~ is obtained. If necessary, the product may be purified by~ for example, chromatography.

Substituted 4-amino-2-oxaindan having the formula (III~, one of the starting materials for preparing the present compound, is prepared, for example, from 4-acetaminophthalide mentioned in Jean Vene and Jean Tirouflet Compt rend 231, 911-12 (1950~.
OH

11 ~ CH M I CH CHN ~ ¦ ~CH3 3 - ` 3 (a) MnO2 C/ ~C/ 3 RlLi Rl c~o\c/cH3 ~11 ~ ~CH3 ~ 11 0 \ / ~CH3 CH3CHN ~ CH3CHN _ tb) (c) ~ ,CH3 H2tPd-C ll 1 \ / ~CH ` (III) (d) wherein Rl is the same as that defined above.

:

. ' ' ! .
. . ,~, , ., "' lL3~7~
g That is, 4-acetaminophthalide is allowed to react with a methyl Grignard reagent such as methylmag-nesium iodide (4-12 equivalents) in an ether solvent such as diethyl ether and tetrahydrofur~n at a temperature from -~0C to room temperature, until diol (a) is obtained.
The diol (a) is allowed to react with activated manganese dioxide (5-20 equivalents) in an ether solvent such as dioxane and ~etrahydrofuran or a halogenated hydrocarbon solvent such as chloroform and dichloroethane under refluxing to obtain lactone (b)7 Then~ the lactone (b) is allowed to react with methyllithium or ethyllithium (2-4 equivalents~ in an ether solvent such as diethyl ether and tetrahydrofuran at a temperature from 30C to room temperature until acetal (c~ is obtained. The acetal (c~ is allowed to react ~ith hydro~en in an alcohol solvent such as methanol and ethanol at room temperature in the presence of catalytic amounts of palladium carbon and conc. hydrochloric acid until anilide (d) is obtained, The anilide (d~ is then allowed to react with alkali metal hydroxide such as sodium hydroxide and potassium hydroxide (5-20 equivalents) in an ethylene glycol and water solvent under refluxing, until substituted ~-amino-2-oxaindan (III) is obtained.

When the present compound is used as an active ing~edient of fungicides, it may be used without adding any other components, but usually, it is formulated into emulsifiable concentrates, wettable powders, suspension formulations, granules, dusts, liquids and the like by mi~ing with a solid or liquid carrier, a surface active agent and other auxiliaries for formulation.

The content of the present compound as an active ingredient in these formulations is 0.1 to 99.9%, preferably 0.2 to 80% by weight.

' ~ ' ' . -' . ......... ' ~ ' ' ':. .
.

- 10~ 7~

The solid carriers include, for example~ fine powders or granules of kaolin clay, attapulgite clay, bentonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite, corn starch powder, walnut shell powder, urea, ammonium sulfate, synthetic hydrated silicon dioxide and the like. The liquid carrier includes for example aromatic hydrocarbons such as xylene, methylnaphthalene and the like, alcohols such as isopropanol, ethylene glycol, cellosolve and the like, ketones such as acetone, cyclohexanone, isophorone and the like, ~egetable oils such as soybean oil, cotton seed oil and the like, dimethyl sulfoxide, acetonitrile, water and the like.

The surface active agents used for emulsification, dispersion, wetting, etc. include, for example, anionic surface active agents such as salts of alkyl sulfate, alkyl (aryl) sulfonates, dialkyl-sulfosuccinates, salts of polyoxyethylene alkylaryl ether phosphoric acid esters, naphthalenesulfonic acid/formalin condensates, etc. and nonionic surface active agents such as polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene block copolymers, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, etc. The auxiliaries for formulation include , for example, lignosulfonates, alginates, polyvinyl alcohol, gum arabic, CMC (carboxymethyl cellulose), PAP (acid isopropyl phosphate), etc.

These formulations as such or diluted with, for example, water are applied to soil or directly to plants.
In more detail, they are used in various forms, e.g., spraying or dusting on plants or spraying, dusting or granule-sprinkling onto soil surface or if necessary, subsequent further soil incorporation. Furthermore, when they are used as seed treating agents, seeds are covered therewith or dipped therein. These formulations may also ', ~ .. :

7 ~ ~ ~
be used in admixture with other fungicides, insecticides, acaricides, nematocides, herbicides, plant growth regulating agent~ fertilizers, soil improvers and the like.

The present compounds are used as an active ingredient of fungicides to be used for paddy field, plowland, orchard, pasture, turf and the like.

When the present compound is used as an active ingredient of fungiclde, its dosage is usually 0.5 to 100 g, preferably 1 to 50 g per are, although it depends on weather conditions, form of formulations, time, method and place of application, diseases to be controlled, crops to be treated, etc. When the emulsifiable concentrate, wettable powder, suspension formulation, liquid formul~tion, etc. are diluted with water for use, the concentration is 0.0001 % to 1 ~, preferably 0.0005 -O to 0.5 %. Granule and dust are used as they are without any dilution.

The present compound is able to be used as an active ingredient of fungicides for various kinds of application5~ since the present compound is remarkably ac~ive against various plant diseases, particularly those ~y microorganisms belonging to Basidiomycetes.
The present invention will be explained in more detail by the following synthesis examples, reference examples, formulation examples and test examples.

Synthesis Example l [Synthesis of compound (2) by method (A)]
To a solution of 80 mg of 1,1,3-trimethyl-2-oxa-4-aminoindan and 50 mg of triethylamine in 5 ml of tetrahydrofuran was added dropwise with stirring below 5C
of inner temperature under ice cooling, a solution of 89 mg of 5-chloro-1,3-dimethylpyrazole-4-carbonyl chloride ', ~

., ~ . .

13~7~3 in 2 ml of tetrahydrofuran, followed by stirring at room temperature overnight. The reaction mixture was extracted with water and chloroform. The organic layer was washed with water, dried and concentrated The residue was purified by silica gel thin layer chromatography to obtain 119 mg of N-(1,1,3-trimethyl-2-oxa-4-indanyl~-5-chloro-1,3-dimethylpyrazole-4-carboxamide.

Synthesis Example 2 [Synthesis of compound (13) by method (A)]
To a solution of 70 mg of 1,1,3-trimethyl-2-oxa-4-aminoindan and 44 mg of triethylamine in 5 ml of tetrahydrofuran was added dropwise a solution of 83 mg of 2-~trifluoromethyl)benzoyl chloride in 2 ml of tetrahydrofuran under stirring at a temperature below 5C under ice cooling, followed by stirring at room temperature overnight. Then the reaction mixture was extracted with water and chloroform. The organic layer Was wa~hed with 5% hydroehlorie aeid and water, dried and eoneentrated. The residue was purified by siliea gel thin la~er chromatography to obtain 102 mg of N-(1,1,3-trimethyl-2-oxa-4-indanyl~-2-(trifluoromethyl)benzamide.

Synthesis Example 3 [Synthesis of compound (19) by method (~)]
A solution of 155 mg of 2-methylnieotinic acid and 335 mg of 1-(3-dimethylaminopropyl)-3-ethylearbodiimide methiodide in 10 ml of methylene ehloride was stirred at room temperature fcr 1 hour. To the solution was added 200 mg of 1~1,3-trimethyl-2-oxa-4-aminoindan and the reaction was made to proceed for 6 hours under refluxing.
To the reaction mixture were added methylene chloride and water to extract an organic layer. The organic layer was concentrated and purified by silica gel thin layer chromatography to obtain 130 mg of N-(1,1,3-trimethyl-2-oxa~4-indanyl)-2-methylnicotinamide.

- 13 - 1~27~

Synthesis Example 4 [Synthesis of compound (24) by method (A)]
To a solution of 100 mg of 1,1,3-trimethyl-2-oxa -4-aminoindan and 63 mg o~ triethylamine in 5 ml of tetrahydrofuran was added a solution of 130 mg of 2-methyl-4-trifluoromethylthiazole-5-caxbonyl chloride in 2 ml of tetrahydrofuran under stirring at inner temperature of below 5 C under ice cooling. After the dropwise addition was over, the reaction mixture was stirred overnight at room temperature, extracted with water and chloroform. The organic layer was washed with 5 %
hydrochloric acid and water, dried and concentrated.
The residue was purified by silica gel thin layer chromatography to obtain 172 mg of N-(1,1,3-trimethyl-2-oxa-4-indanyl)-2-methyl-4-trifluoromethylthiazole-5-carboxamide.

Synthesis Example 5 [Synthesis of compound (26) by method (B)]
A solution of 193 mg of N-(1,1,3-trimethyl-2-oxa-4-indanyl)-2-chloroacetoacetamide and 49 mg of thioacetamide in lO ml of tetrahydro~uran was allowed to react for 3 hours under reflu~ing.
To the reaction mixture was added 90 mg o~
anhydrous potassium carbonate and the mixture was allowed to react for 4 hours under refluxing. ~fter the reaction was over, thereto were added chloroform and water to separate an organic layer. The organic layer was dried, concen-trated and purified by silica gel thin layer chromatography to obtain 89 mg of N-(1,1,3-trime-thyl-2-oxa-4-indany~-2,4-dimethylthiazole-5-Carboxamide.

Some of representative compounds of the present invention which are able to be produced by these methods are shown in Table 1.

, ~ .. , '~ . .. ~,. ' '.

~ 14 - ~3275~

Table 1 Compound represented by the formula:

~ \ / 3 A - C - NH- ~ ~`CH3 Compound No. -~ Rl Melting point ) rH3-N ~ ¦ CH3 . ~ ~

CH3 - N ~ CH3 16~.1 - CH3 . _ __ ~4) CH3 - N ~ CH3 101.3 _ _ CH3 _. .

' ¦ ~ H
.

. ~ , -' , ~ 3~7~

. . _ ~ , ( 6 ) N~ CH3 CH3-- N ~/

__ _ / .. ___ ( 7 ) CH3 _ Nl ~1 CH3 15 6 . 4 . .,. _ __ . . __ (8) CH3-- l~ CH3 160.5 C2H5 ~ ..... .

9 ) CH3--~ CH 9 9 . 2 . _~ , . . ._ ._ ( 10 ~ N~ C2H5 139 . 9 CH3 ~

CH3 .. _~ .__ ( 11 ) N ~ C2H5 _ . _ CH3-- l ~ -- --------------.

1327~3~

( 12 ) \ CH3 CH3 141. 8 (13) C~3 CH3 188.6 .

( 14 ) Cl CH3 129 . 9 ( 15 ) 8r ,_ _ .

(16) ~ c~3 171.4 I

( 17 ) ~ CH3 189 . 6 _ __ . _ ( 18 ) ~ Cl CH3 153 .1 _ . _ ( 19 ) ~CH3 CH3 161.1 . _ (20) ~\CF3 H3 187.4 _ .

~L~27~

(21) ~ \ l CH3 156.5 (22) ~ CH3 161.4 (23) Cl ~ ~ C 3 lg9.1 _ CF3 ~ __ _ (24) CH ~ ~S ~ CH3 167.5 _ . _ (25) Cl / ~S CH3 93.0 . _ iCH 3 .__ .

(26) ~ ~ - CH3 134.8 _ _ _ _ _ :' ~27) H2N/ S3 CH3 189.0 _ ~j CH3 ~ S CH3 . .

, ~'' :', .~. ', : ~

~ ~7~

Preparation of substituted 4-amino-2-o~aindan represented by the formula (III) will be explained below.

Reference Example 1 Synthesis of a,~-dimethyl-2-hydroxymethyl-3-acetaminobenzyl alcohol.
To a mixture of 9.5 g of metallic magnesium and 60 ml of diethyl ether was slowly added with stirring a solution of 56 g of methyl iodide in 120 ml oE diethyl ether. The mixed solution was heated for 15 minutes under refluxing and cooled. The solution of methylmagnesium iodide thus ~repared above in ether was slowly added with s-tirring at inner temperature of below 10 C to a solution of 7.5 g of a-acetaminophthalide in 120 ml of tetrahydrofuran, followed by stirring at room temperature overnight. After the reaction was over, the reaction mixture was poured into aqueous ammonium chloride solution (saturated) under ice cooling and extracted twice with 400 ml of ethyl acetate. The combined extracts were dried and concentrated to obtain an oily substance. The oily substance was purified by silica gel colurnn chromatography to obtain 7.2 g of a~a-dimethyl-2-hydroxymethyl-3-acetaminobenzyl alcohol in the white crystal form. m.p. 137.9 ~C
'H-NHR (CDCl3) ~ppm 1.6 (6H, s), 2.1 (3~, s), 3.7 (2H, br s), 5.0 (2H, s), 7.2 - 7.8 (3H, m), 8.7 (lH, br s) Reference Example 2 Synth~sis of 3,3-dimethyl-7-ac~tamino~hthalide.
To a solution of 7.2 g of a,~-dimethyl-2-hydroxymethyl-3-acetaminobenzyl alcohol in 300 ml of chloroform was added 28 g of activated manganese dioxide and the mixture was allowed to react for 6 hours ~nder refluxing After the reaction was over, the reaction mixture was left to stand for cooling and filtered on a glass filter having a bed of celite(trade-mark). The residue was washed with 100 ml of ;~

: ; : ~

~27~

chloroform. The filtrate and the washed solution were combined and concentrated to obtain an oily substance. The oily substance was purified by silica gel column chromato-graphy to obtain 4.4 g of 3,3-dimethyl-7-acetaminophthalide in the white crystal form. m.p. 124.1 C.
'H-N~R ~ppm 1.6 (6H, s), 2.2 (3H, s), 7.0 (lH, d, J=8.0 Hz), 7.6 (lH, t, J=8.0 Hz), 8.5 (lH, d, J=8.0 Hz), 9.7 (lH, br s) Refexence Example 3 Synthesis of 1,1,3-trimethyl-3-hydroxy-2-oxa-4-acetaminoindan.
To a solution of 4.4 g of 3,3-dimethyl-7-acetamino-phthalide in 80 ml of tetrahydrofuran was slowly added dropwise 43 ml of a solutlon of methyllithium in ether (1.4 M) at 20 C, followed by stirring at the same temperature for 20 minutes. After the reaction was over, the reaction mixture was poured into aqueous ammonium chloride solution (saturated) under ice cooling and extracted twice with 200 ml of ethyl acetate. The combined extracts were dried and concentrated to obtain 4.7 g of 1,1,3-trimethyl-3-hydroxy-2-oxa-4-acetaminoindan as an oily substance.
'H-NMR ~ppm 1.5 (6H, s), 1.7 (3H, s), 2.1 (3H, s), 4.7 (lH, s), 6.85 (lH, d, J=8.0 Hz), 7O3 (lH, t, J=8.0 Hz), 7.9 (lH, d, J=8.0 Hz), 8.0 (lH, s) Reference Example 4 Synthiesis of 1,1,3-trimethyl-2-oxa-4-acetaminoindan.
To a solution of 4.7 g of 1,1,3-trimethyl-3-hydroxy-2 oxa-4-acetaminoindan in 120 ml of ethanol were added catalytic amounts of conc. hydrochloric acid and 10 %
palladium carbon, and vigorously stirred for 6 hours at room temperature under a hydrogen atmosphere. After the reaction was over, the reaction mixture was filtered on a - "

.

1 ~ 2 ~

glass fil~er having a bed of celite and the residue was washed with 60 ml of ethanol. The filtrate and the washed solution were combined and concentrated to obtain 4.3 g of 1,1,3-trimethyl-2-oxa-4-acetaminoindan in the oily substance form.
'H-NMR ~ppm 1.4 (3H, s), 1.4 (3H, d, J=6.0 Hz), 1.5 (3H, s), 2.1 (3H, s), 5.4 (lH, q, J=6.0 Hz), 6.8 - 7.4 (3H, m), 8.1 (lH, s~
Synthesis Example 8 Synthesis of 1,1,3-trimethyl-2-oxa-4-aminoindan.
To a solution of 4.3 g of 1,1,3-trimethyl-2-oxa-4-acetaminoindan in 60 ml of ethylene glycol and 30 ml of water was added 11 g of potassium hydroxide and the mixture was heated under refluxing for 8 hours under a nitrogen atmosphere. After the reaction was over, the reaction mixture was left to stand for cooling, diluted with 60 ml of water and extracted with 60 ml of chloroform four times. The combined extracts were washed with water three times, dried and concentrated. The oily substance obtained was purified by silica gel thin layer chromatography to obtain 2.0 g of 1,1,3-trimethyl~2-oxa-4-aminoindan in the white crystal form. m.p. 75.5 C
'H-NMR ~ppm 1.4 ~3H, s), 1.5 (3H, d, J=6.0 Hz), 1.5 (3H, s), 3.6 (2H, br s), 5.25 (lH, q, J=6.0 Hz), 6.2 -6.7 (2H, m), 7.1 (lH, dd, each J=6.0 Hzj Synthesis Example 9 1,1-Dimethyl-3-ethyl-2-oxa-~-aminoindan was obtained by the similar method to Synthesis Example 8.
'H-NMR ~ppm 1.0 (3H, t, J=6.0 Hz), 1.45 (3H, s), 1.55 (3H, s), 1.4 - 2.1 (2H, m), 3.5 (2H, br s), 5.15 ~lH, dd, J=6.0 Hz, 4.0 Hz), 6.45 (2H, br d), 7.0 (lH, dd, J=8.0 Hz, J=6.0 Hz) .
.

~27~38`~

The following ar~ formulation e,camples where the present compounds used are indicated by the numbers given in Table 1 and Synthesis Examples and parts are by weight.
s Formulation Example 1 Fifty parts of each of the present compounds (1) - (28), 3 parts of calcium lignosulfonate, 2 parts of sodium lauryl sulfate and 45 parts of synthetic hydrated silicon dioxide are thoroughly pulverized and mixed to obtain a wettable powder containing an active ingredient concentration of 50 %.

Formulation Example 2 Ten parts of each of the present compounds ~ (28), 14 parts of polyoxyethylenestyrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 70 parts of xylene are thoroughly mixed to obtain an emulsifiable concentrate containing an active ingredient concentration of 10 %.

Formulation Example 3 Two parts of each of the present compounds ~ (28), 1 part of synthetic hydrated silicon dioxide, 2 parts of calcium lignosulfon~te, 30 parts of bentonitP, and 65 parts of kaolin clay are thoroughly pulveri7ed and mixed, well kneaded with water, then granulated and dried to obtain a granule containing an active ingredient concentration of 2 ~.
Formulation Example 4 Twentyfive parts of each of the present compounds (1~ - (28), 3 parts of polyoxyethylenesorbitan monooleate, 3 parts of CMC and 69 parts of water are mixed and wet-pulverized to particle size of not more .. ~ .

- 22 - ~ ~ ~7~

than 5 microns to obtain a suspension formulation containing an active ingredient concentration of 25 ~.

Formulation Escample 5 Two parts of each of the present compounds (1) - (28), 88 parts of kaolin clay and 10 parts of talc are thoroughly pulverized and mixed to obtain a dust containing an active ingredient concentration of 2 ~.

Formulation Example 6 Ten parts of each of the present compounds ~ (28), 1 part of polyoxyethylenestyrylphenyl ether and 89 parts of water are mixed to obtain a liquid containing an active ingredient concentration of 10 ~.
The effect of the present compounds as an active ingredient of fllngicides will be shown by the following test examples. The present compounds used are indicated by the compound number given in Table 1 and Synthesis Examples and the compounds used for comparison are indicated by the compounds given in Table 2.

, :
, . -~
.. . ..
.

- 23 - ~ 3 2 7 ~ ~

Table 2 Compounds Chemical formula Note _ _ Commercially A ~ CH3 OC3H7(i) avai able O (mepronil) ___ _ _ N CH3 3 7(i) mentioned in B CH3-N ~ C NH - ~ Japanese _ . ... _ Compound N CH3 mentioned in CCH3 _ ~ ~ C NH ~ 1164 ~ 1159 O (1970) . . _.. __ ,_ CH3 OC3H7(i) Compound Japanese ¦ C - NH ~ ~ K ka 58-. , :: .:: , : ~ , ,, ~327~

The controlling effect is de~ermined b~
observing with the naked e~e the condition of disease of tes~ plants on examination, namely, the degree of fungus colony and infected area of leaf and stem and grading the condition of diseases into the followiny six indices 0, l, 2, 3, 4 and 5:
S .O.... No infected area and fungus colony are noticed.
4 ...... Infected area and fungus colony are noticed in about lO % of leaf and s.em.
3 ...... Infected area and fungus colony are noticed in about 30 % of leaf and stem.
2 ~ Infected area and fungus colony are noticed in about 50 % of leaf and stem.
1 ...... Infected area and fungus colony are no~iced in about 70 ~ of leaf and stem.
0 ...... Infected area and fungus colony are noticed in more than about 70 ~ and no difference is noticed from the condition of disease when no compound is used.

The above grading is applied to all of the following test examples.
Test Exarnple 1 Test for preventive controlling effect on sheath blight (Rhizoctonia solani) of rice.
Sandy loam was filled in a plastic pot and rice (var.: K,inki ~lo. 33) was sowed and cultivated in a greenhouse for 20 days to grow to seedlings in the 4-5 leaf stages. The test compounds were formulated into emulsifiable concentrates in accordance with the Formulation Example 2 and they were diluted with water to a given concentration. These were foliar-spra~ed onto the seedlings to allow them to thoroughly deposit :

~7~

on the leaf surface. After 4 hours frcm the spral~ing, the seedlings were inoculated with agar piece containing Rhizoctonia solani. After inoculation, the seedlings were grown at 28C for 4 days under highly humid condition and the contro'lling effects were observed.
The results are shown in Table 3.

Table 3 Concentration of active Controlling Test compounds ingredient (ppm) effect .

(1) 25 5 - 50 5 ~
(2) 25 5 __ _ 50 _ _ .
(5) 25 5 (7) 25 5 ''' ' ~ ~27~

(8) 55 ( 9) 50 5 _______ ~0 _ _ _ _ _ _ (10~ 25 5 (12) 50 5 _ -50 5 (13) 25 ~ 5 (14) 25 5 (16) 25 5 _ 50 - - 5 (17) 25 5 . .
.. . .
, 7 ~ ~ ~

. 50 - ' .
( 18) 25 5 ( 19) 25 5 _ (20) 25 5 (21) 25 5 _ . .~ l S
(22) 25 5 _ _. __ .
(23) 50 _ 5 _ _, (24) 50 5 ~-(25) 50 5 ....__ .
(26) 50 5 _ I
l (27) 50 5 . ._ _ . ,~ r ~1 327~

=

' ' ' ~ ', .
. .
: :.. : ~

- 29 ~327~

Test Example 2 Test for systemic controlling effect on sheath blight (Rhi7Octonia solani) of rice.
Sandy loam was filled in a 130 ml plastic pot and rice (var.: Kinki No. 33) was sowed and cultivated in a ~reenhouse for 3 weeks to grow to seedlings in the 4 - 5 leaf stages. The test compounds formulated into wettable powders in accordance with Formulation Exmple 1 and they were diluted with water and drenched in a given amount to the soil. After drench, the seedlin~s were grown in a greenhouse for 7 days and inoculated with agar piece containing .Rhizoctonia solani.
After inoculation, the seedlings were grown at 28~C for 4 days undex a highly humid condition and the controlling effect was obser~ed~ The results are shown in Table 4.

Table 4 . _ . _ ~ _ Test compounds Dosage of active Controlling lngredlent (g/10~) effect ._ -(1) 200 5 .. __ .. ~
. . 200 5 ~- S

.. . _ ._ _ _ . . . _ . _._ .
(5) 200 5 _ ._ _ _ ._ (7~ 200 5 . ,_ _ ,__ - .

', ~ 327~

(8) ~ 200 S

(9) 200 5 _ (12) 200 5 (13) _ 200 5 (14) 200 5 (16) 1 200 1 5 (17) - 200 - 5 - (l8) - 200 = 5 (19) 200 _ 5 (20) 200 _ 5 (21) 200 5 (22) 1 200 5 (23) 1 200 1 5 (24) 1 200 1 5 . ~ ;
(25) j 200 1 5 (26) 1 200 ! 5 : . ' ''' ~

- 31 - ~27~

lO~ 0 _ _ __ _I

, 0 Test Example 3 Test for controlling effect on southern blight (Corticium rolfsii) of kidney bean.
Sandy loam well mixed with Corticium rolfsii which was previously cultured in bran medium was filled in a 250 ml plastic pot and kidney bean (var.:

Taishokintoki) was sowed. The test compounds were formulated into wettable powders in accordance with Formulation Example 1 and diluted with water. A given amount of the test compound was drenched into the soil.
After the drench, cultivation was made for 3 weeks in a greenhouse and controlling effect was examined by observing the degree of disease of the stem in the vicinity of the soil surface. The results are shown in Table 5.

.
~ . ~
.; :

, . ~ . , : , - 32 - ~ ~ ~7~

Table 5 . ___ . . _ Dosage of active Controlling Test compounds ingredient (g/lOa) effect _ . .. ___ . _~
(1) 200 5 (2~ 200 5 . _~ . . _ .
(3) 200 5 , (4) 200 5 _ (5) 200 5 _ (7) 200 5 _ _ (8) 200 5 (9) 200 5 (10) 200 5 __ .
(12) 200 5 (13) 200 5 .
(14~ 200 5 _ (16~ 200 5 (17~ 200 _ ~
(18) 200 - 4 (19) 200 5 (20~ 200 5 ___.
(21~ 200 5 _ (22~ 200 5 ~23~ 200 5 (24) 200 5 (25~ 200 5 . .__ ....
(261 200 5 . _ _ _ (27l 200 _ 5 .

, ~27~

.

~ _ .

0 Test Example 4 Test for curative controlling effect on brown rust ~Puccinia recondita) of wheat.
Sandy loam was filled in a plastic pot and wheat (var.: Norin No. 73J was sowed and grown in a greenhouse for 10 days to seedlings of the 2 - 3 leaf stages, which were inoculated with spores of Puccinia recondita. After inoculation, the seedlings were grown at 23C for one day under a highly humid condition and onto these seedlings was foliar-sprayed the test compound formulated into emulsifiable concentrate in accordance with Formulation Example 2 and diluted with water to a given concentration, so that the compound was thoroughly deposited on the leaf surface. After spraying, the seedlings were cultivated at 23C for 7 days under illumination and the controlling effect was observed. The results are shown in Table 6.

3.~2~

Table 6 . . ~ . . _ Concentration of active Controlling Test compounds .
lngredlent (ppm) effect . . . _ . . .
(1) ~ 500 5 (2) 1 500 5 _ I _ (3) 1 500 5 .
(4) 500 5 ___ _ (5) 500 5 (7) 500 5 1~- __ I (8) 500 5 _ _ _ (g)_ _ 500 5 _ _ _ (10~ 500 : 5 . _ (12) 500 5 _ (13) 500 S
(14) 500 5 . ._ . (16) 500 5 (17~ 500 5 (18~ 500 5 : (19l 500 5 _~ _ _ _ (20) 500 5 .
(21) 500 5 (22) 500 5 _ _ _ .
(23~ 500 5 _ (24) 500 5 . .. _ ___. ~
(25~ 500 5 (26~ ~ 500 5 (27~ 500 5 : , , . ,:
', ' , , ' ''~" ' ' ' .

Claims (12)

1. A substituted carboxylic acid derivative having the formula:

wherein R1 stands for a methyl or ethyl group, A stands for , or , R2 stands for a methyl, ethyl or trifluoromethyl group, R3 stands for a methyl group or a halogen or hydrogen atom, R4 stands for a fluorine or hydrogen atom, R5 stands for a methyl, nitro or trifluoromethyl group or a halogen atom, Z stands for a =CH- group or an N atom, R6 stands for a methyl, ethyl or trifluoromethyl group and R7 stands for an amino or methyl group or a chlorine atom.

2. A substituted carboxylic acid derivative having the formula:

wherein R1 stands for a methyl or ethyl group, R2 stands for a methyl, ethyl or trifluoromethyl group and R3 stands for a methyl group or a halogen or hydrogen atom.

3. A substituted carboxylic acid derivative having the formula:
wherein R8 stands for a methyl or trifluoromethyl group and R9 stands for a halogen atom.

4. .

5. .

6. .

7. A substituted 4-amino-2-oxaindan having the formula:
wherein R1 stands for a methyl or ethyl group.

8. A process for preparing a substituted carboxylic acid derivative having the formula:

where R1 stands for a methyl or ethyl group, A stands for , or , R2 stands for a methyl, ethyl or trifluoromethyl group, R3 stands for a methyl group or a halogen or hydrogen atom, R4 stands for a fluorine or hydrogen atom, R5 stands for a methyl, nitro or trifluoromethyl group or a halogen atom, Z stands for a =CH- group or an N atom, R6 stands for a methyl, ethyl or trifluoromethyl group and R7 stands for an amino or methyl group or a chlorine atom, which comprises allowing a substituted carboxylic acid having the formula:

A - COOH

wherein A is the same as that defined above, or a reactive derivative thereof, to react with a substituted 4-amino-2-oxaindan having the formula:

wherein R1 is the same as that defined above.

9. A process for preparing a substituted carboxylic acid derivative having the formula:

wherein R1 stands for a methyl or ethyl group, R6 stands for a methyl, ethyl or trifluoromethyl group and R10 stands for an amino or methyl group, which comprises allowing a substituted 4-amino-2-oxaindan derivative having the formula:

wherein R1 and R6 are the same as those defined above, to react with a thioamide derivative having the formula:

wherein R10 is the same as that defined above.

10. An agricultural or horticultural fungicide which contains, as an active ingredient, a substituted carboxylic acid derivative having the formula:

wherein R1 stands for a methyl or ethyl group, A stands for , or R2 stands for a methyl, ethyl or trifluoromethyl group, R3 stands for a methyl group or a halogen or hydrogen atom, R4 stands for a fluorine or hydrogen atom, R5 stands for a methyl, nitro or trifluoromethyl group or a halogen atom, Z stands for a =CH- group or an N atom, R6 stands for a methyl, ethyl or trifluoromethyl group and R7 stands for an amino or methyl group or a chlorine atom with an inert carrier.

11. A method for controlling fungi which comprises applying to fungi a fungicidally effective amount of a substituted carboxylic acid derivative having the formula:

wherein R1 stands for a methyl or ethyl group, A stands for , or R2 stands for a methyl, ethyl or trifluoromethyl group, R3 stands for a methyl group or a halogen or hydrogen atom, R4 stands for a fluorine or hydrogen atom, R5 stands for a methyl, nitro or trifluoromethyl group or a halogen atom, Z stands for a =CH- group or an N atom, R6 stands for a methyl, ethyl or trifluoromethyl group and R7 stands for an amino or methyl group or a chlorine atom, to fungi.

12. The method according to claim 11 wherein the fungi are a plant pathogenic fungi.