AU427668B2 - Novel n-phenylcarbamate derivatives - Google Patents

Description

1452 8 !70 n The present invention relates to novel antimicrobial

compositions and active compounds therefor. the 'The said antimicrobial compositions contain as compounds active ingredient at least one of N-phenylcarbamate

of the formula: x RL

/R 3 X1

wherein and R2 are each hydrogen or lower alkyl (e.g,

ethyl, n-propyl, isopropyl, butyl, isobutyl, t-" methyl,

butyl), R is cyano, carboxylora group of the formula:

-COOR 4 or -CON'R5 wherein R4 is lower alkyl methyl, SRs t-butyl) ethyl, n-propyl, fsopropyl, n-butyl, isobutyl,

and R 5 and R6 are each hydrogen or lower alkyl methyl,

ethyl,'n-propyl, isopropyl,.n-butyl, isobutyl, t-butyl),

and X and X' are each halogen, provided that R1 and R 2 are

both hydrogen or same or different lower alkyl when R is

cyano and that R and R are each lower alkyl when R is

carboxyl or the group of the formula: -CCOR 4 wherein R4

is as defined above.

It has now been found that the said N-phenylcarba-

mate compounds exhibit a strong antimicrobial activity

against a wide variety of microorganisms including phytopatho This genic fungi and parasites of industrial products. finding is of unexpected and surprising property,.because

their analogous compounds, i.e, those bearing no or one

halogen atom on the benzene ring or having two halogen

atoms but not at the 3 and 5-positions, show no appreciable

_antimiropbilactivity- jtill, it is advantageous that the

2- 27,6 8

14,52 8/70 N-phenylcarbamate compounds do not substantially show any chemical injury on plants and any toxicity in fishes, mammalian animals and human beings.

A basic object of the present invention is to embody the novel antimicrobial compositions, Another object of this invention is to embody novel N-phenylcarbamate com- pounds having a marked anti-microbial activity. A further object of the invention is to embody a process for preparing the novel N-phenylcarbamate compounds. These and other objects will be apparent to those conversant with the art

to which the present invention pertains from the subsequent

descriptions.

According to the present invention, the N-phenyl- carbamate compound may be prepared by reacting a dihalo- aniline of the formula:

X

X1 wherein X and X' are each as defined above with a haloformate of the formula:

2 [11 0 R3 wherein X" is halogen chlorine, bromine) and R, R2 and Rt are each as defined above in the presence of -an acid- eliminating agent.

Examples of the dihaloaniline [II] are fluoroaniline, 3,5-dibromoaniiine, 3,5-diiodoaniline, 3-

3-chloro-5-iodoaniline, etc. As the

14_ 52 8170 haloformate [III), there may be exemplified abxmty C~y3e~ chloroform]a~, ethoxY- chiaroformfate, metho xycarbonylmfethyl chio ro- caIrbonylmethy)l chiorofo rmat e, p ropoxycarboflYlmethY' e, methoxy6Larbonyl- formate, carbO xyisopropYl chio0roformat sop ropYl phloi'o- i sopropY). chloroformfate, ethoxycarboflyli chioroformate, butoxY- fo nnate, propoxycarboflylisopl'opyl 1 sopropyl chio roformat e, a- carbo xy-a-methylPrOPY carbonyli @h~O chiorofo rmat e, a-ehycroylamtypoy ropyl chio rof~ rmate, format e, a- ethoxycarbofylamethylp xy- ropyl ohio rofo rmat e, 4buto a-propoxycarboflla-methylP a-toy~bnla carbonyl-a-methylpropyl chiorofonflate, ethoxycarbofyl-la-m6tYl amll methylbutyl chioroformfate, a- ethylbutYl c1g§rofonfat e, chiorofo rmat e, a- etho xy carboflyl-L- a- a-cyano ethyl c brof@ate, cyanomethyl chioroformfate, 1 a- cyaxio-a-mlethylpTOPY OhiboI cyanoi sop ropyl chi orofo rmat e, chia rofo rmat e, darbamoyl- format e, a- cyaxio-a-methylb utyl chlorof~ipmate, a- methyl chioroformfate, a-carbamoylethyl N-methyl carb aioylm ethyl carbamfoylisopI'opyl chioroformfate, ethyl chliiOVformate, chiorofo rmate, a- (N-m ethyl carbamoyl) chic roformate, N, 1-diethYi- a- (N-methyl carbamoyl) isopropyl a-(N,N-dillet1~yldrbaMOYl)- carbamoyllfethyl chioroformfate, ethyl chioroformate, N,N-dimethylcarbamfoyl)§PPXOPYI

chioroformfate, etc by ifatilg the The reaction is usually effected amount of th~e haloforMP-te dihaloaflilifle [III with an equiniolar ag~t such as

[I]in the presence of an acid-eliminfating pyridifle, triethylalifle, dip ethylaniline, tertiary amine in an inet Polverit diethylaflilifle, N-methylmforpholine) ch o rob eftlie, dichioro- benzene, toluene, xylene, mono carbon tetrachloide, ether) ethane, t-etrachi oro ethylene,

4 417,6 68 from at a temperature fo01to 50'C while stirring. The product can be readily recovered from the reaction mixture by washing the latter with water and evaporating the solvent therefrom. Alternatively, the N-phenylcarbainate compound [I] may be prepared by reacting a phenylisocyanate of the foimula: x

NCO [IV]

Xf wherein X and X' are each as defined above with an alcohol of the formula:

R, HO-C-RIV 2 v R3. wherein 1, R2 and R3are each as defined above. Examples of the phenylisocyanate [IV] are difluorophenylisocyanate, 3, 5-dibromophenylisocyanate, di iodophenylisocyanate, etc. As the alcohol IV], there may be exemplified glycolic acid, methyl glycolate, ethyl glycolate,_propyl glycolate,- a,a-dimethylglycolic acid, methyl a,a-dimethylglycolate, ethyl a,a-dimethylglycolate,

propyl a ,a-dimethylglycolate, butyl a, a-dimethylglycolate,, a-methyl-a- ethylglycoli c acid, methyl a-methyl-a- ethyl- glycol ate, ethyl a-methyl-a- ethyiglycol ate, p ropyl a-methyl- a-ethylglycol ate, butyl a-methyl-a- ethylglycolate, ethyl a-methyl-a-propy-Iglycolate, ethyl a-methyl-a-butylglycolpate, ethyl a- ethyl-a-propylglycolat e, hydroxyacetonxiitrile, lacto-_ itrile, acetone cyanohydrin, a-ethyl-a-hydroxyactontrile,

s-5 427668

.11.1528/70 a- ethyll actoni trile, a-propyllactontril e, glycolamide, 1actani-de, a-hydroxyi sobutyraxride, N-methylglycolamflde,

N-methyllactami de, N-m ethyl- a-hydroxyi sobuty rani de, N, N- cliiethylglycolamide, N,1N-di methyllactamide, N,N-dimethy1-

a-~hydroxyisobutyralide, etc.

The reaction is ordinarily carried out by treating

the phenylisocyaiate [IV] with an equimolar amount of the benzene, toluene, alcohol in an' inert solvent

xylene, isopropyl ether, tetrahydrofilrafl, chloroform, carbon

tetrachloride), if necessary, in the presence of a catalytic

amount of tertiary amine triethylamine, pyridine,

dirnethyl aniline, diethylaniline, N-methylmorpholine) at a 0 temperature from room temperature to 100 C. The product can be easily recovered from the reaction mixture by evapor tion of the solvent. Alternatively, the N-phenylcarbafate compound [I]

may be prepared by reacting an.1N-phenylcarbamfoyl halide of the formula: x

NHC-XII [VI]

whe rein X, X' and X" are each as defined above with the achL[v in the presence of an acid-eliminating agent.

Examples of the N-phenylcarbamoyl halide [VI] are chloride,

phenyl) carbamoyl chloride, 3,5-diiodophenyl) carbamoyl

chloride, 3-chloro-5-bromophe-nllcarbamoyl chloride,

3-chloro-5-iodophenyl) carbamoyl chloride, etc. Examples

of the alcohol [VI] are as described above.

-427.6i

14 52 8/70 The reaction is normally performed by treating the

N-phenylcarbamoyl halide [VI] with an equimolar amount of

the alcohol in the presence of an acid-eliminating agent

such as tertiary amine pyridine, triethylamine, di-

methylaniline, diethylaniline, N-methylmorpholine), favorab-

ly in an inert solvent benzene, toluene, xylene, mono-

chlorobenzene, chloroform, isopropyl ether, ether, carbon 0 tetrachloride) at a temperature from 0 to 50 C while stirring.

The product can be recovered from the reaction mixture by

washing the latter with water and 5 hydrochloric acid,.

drying the washed organic solvent layer and evaporating the

solvent therefrom.

Among the thus obtained N-phenylcarbamate com-

pounds, those of the formula in which R, and R2 are

each hydrogen or lower alkyl, R3 is cyano, carboxyl or a

group of the formula: -COOR or -CON(R 4 wherein R4 is R, lower alkyl and R5 and R6 are each hydrogen or lower alkyl,

and X and X' are each halogen, provided that X and XI are

not simultaneously chlorine when R is cyano, that R1 and

R2 are each lower alkyl and X and X' are not simultaneously

chlorine when R is the group of the formula: -COOR 4

wherein R4 is as defined above and that R1 and R2 are each

lower alkyl when R3 is carboxyl, are novel compounds.

As stated above, the N-phenylcarbamate compounds

of the present invention exert a strong antimicrobial.

activity against various microorganisms including phytopatho-

genic fungi Pyricularia oryzae, Cochliobolus miyabeanus,

Xanthomonas oryzae, Xanthomonas citri, Sphaerotheca fuliginea,

Pellicularia sasakii, Pellicularia filamentosa, Fusarium

oxysporum,_Corticium rolfssi ,_Botrytis .cinerea, Sclerotinia

-7- 427.668

28/70 sci ero tia rum, Al ternaria kikucliana, Al ternaria mali, Glomere]E cingul at a, Py thi ur a-ohani dermatum, Helminthospoiurn sigmoidium and parasites of industrial products Aspergilnus niger). Thus, the N-phenylcarbaxnate compounds are useful as antimicrohial agents,- particularly in the field of agricultural fungicides and industrial fungicides, and are further expected to be useful as pharmaceutical microbicidei In other words, they may be used as eigricultural chemicals for prevention or inhibition of plant -diseases caused by phytopathogenic fungi and bacteria. They may be also used as industrial chemicals for prevention or inhibition of staining on industrial products. The N-phenylcarbainate comnounds of the formula in which R13 is carboxyl may be used in the form of alkaline metal salt as well as free acid. For the said use, the N-phenylcarbamate compounds may he employed as such but, in most practical cases, are extcnded with a suitable carrier(s) to make a con- ventional preparation form such as dust, wettable powdert oil spray, aerosol, tablet, emulsifiable. concentrate, pellet or granule. Besides the N-phenylcarbamate compounds these antimicrobial compositions may contain one or more fungicides Blasticidin S, Kasugamycin, Polyoxctn, Cellocidin, 2-C3, 5-dimethyl-2-oxocyclohexyl)2-hydroiW- cthyllglytarimide, streptomycin, griseofulvin, pentachloro- nitrob enzene, pentachlorophenol, hexachlorob enzene, p enta- chlorobenzyl alcohol, -pentachlorobenzaldoxime, 2, 6-dichioro- 4-ni troani line, zinc ethyl enebis( dithiocarbainate), zinc dimethyl thiocarbamate, mahganous -ethyl enebi s( dithiocarbainate) bis(dii.-cthylthiocarba moyl)disulfjLde 2,4,5,6-tetrachloro- isophthnlonitrile, 2, 3-dichlor-o- 4-naphthoquinone,, tetra-

8- 427.6 68

14- r/O chloro-p-b enzoquinone, p-dimethylaminobenzenediazosodium sulfonate, 2- C -methyiheptyl 6-dim. trophenyl crotonate, 2-heptadecylimidazoline acetate, 2, 7-di chloro-6-C o-ghloro- anilino) -S-triazine, dodecylguani dine acetate, 6-methyl- 2, 3-quinoxalinedithiol cyclic S, S-dithiocarbonate., 2,3- quinoxalinedi thiol cyclic tri thiocarbonate, N-tricbloro- methylthio-4-cyclohexene-l, 2-dicarboxyimide, 2,2- tetrachioro ethyithia) cyclohexene-l, 2-di carboxyimide, N-C 3, 5-dichlorophenyl)ma-leimide, N-C 3, succinimide, N-C 3, 5-dichlorophenyl)itaconimide, 5-dimethyloxazolidine-2,4-dione, 2, 3- carboxanilido- 6-methyl-l, 4,4-di oxide- 2,3- carbo xanilido-6-methyl- 4-oxazine, 1- (N-n-butyl- carbaxoyl)-2-methoxycarbonylaminobenzimidazole, 0,0- diethyl- S-b en zyiphosphorothi oat e, 0-ethyl-S, S-diphenylphosphorodi- thioat e, 0-butyl-S-b cnzyl-S-ethylphosphorodithioate, 0- ethyl-0-phenyl-0-( 2,4, 5-trichlorophenyl)phosphate, 0,90- dirnthyl-0-( 3-methyl-4-nitrophenyl)phosphorothioate, 2- bis( ethoxyvcarbonyl) ethylll-0,0-direthylphosphorodithioate,, 0,0 dimethyl-S-(N-methylcarbanoylmethyl)phosphorodithoate, 0,0-di eth-yl-0-( 2-i sopropyl- 6-rncthyl-4-pyimidyl) thiophosphate, 3,4-dirnethyiphenyl N1-methyl carbainate, i ron inethylarsonate, 2-chloro-4, 6-bis( ethylamino)-s-triazine, 2,4-dichlorophenoxy- acetic acid and its salts and esters, 2-methyl-4-chloro- phenoxyacetic acid and its salts and esters, 2,4-dichioro- phonyl-4 '-ni trophcnyl ether, sodium pentachlo rophenolate, N-C 3, 4-dichlocrophenyl) propionamide, 3-C 3,4-dichlorophenyl)- 1 ,l-dimethyluarea, a, a, a-trifluoro-2, 6-dinitro-N, N-di-n- propyl-p-toluidine, 2-chloro-2' ,6'-diethyl-N-(rnethoxymethyl)- acetami de -naphthyl 11-methylcarbamatc, 1~ methyl N-C(3,4-

9 427. 68

14, 52 8/70 dichlorophenyl)carbamate, 4-chlorobenzyl N,N-dimethylthiol-

carbamate, N,N-diallyl-2-chloroacetamide, ethyl P-(2,4-

dichlorophenoxy)acrylate, cyclobexyl 0-(2,4-dichlorophenoxy)-

acrylate, etc.). The microbial compositions may also contain

one or more materials known to be active as insecticides, acaricides, herbicides, fertilizers, soil con- nematocides,

ditioners, soil disinfectants-or plant growth regulators.

Examples of typical microbial compositions accord-

ing to this invention are:

Dusts obtained by dispersing at least one of

the N-phenylcarbamate compounds as the active ingredient

in a concentration of 0.1 to 50 by weight in an inert

carrier talc, diatomaceous earth, wood flour, clay).

Wettable powders obtained by dispersing at

least one of the N-phenylcarbamate compounds as the

active ingredient in a concentration of 0.1 to 80 by

weight in an inert adsorbent carrier diatomaceous

earth) together with a wetting and/or dispersing agent

such as an alkali metal salt of a long aliphatic sulfate

chain, a partly neutralized sulfuric acid derivative of

either a petroleum oil or a natural occurring glyceride or

a condensation product of an alkylene oxide with an organic

acid.

Emulsifiable concentrates obtained by dispers-

ing at least one of the N-phenylcarbamate compounds as

the active ingredient in a concentration of 0.1 to 50

by weight in an organic solvent dimethylsulfoxide)

plus an emulsifier such as an alkali metal salt of a long

aliphatic sulfate chain, a partly neutralized sulfuric acid

derivative of either a petroleum oil or a natural occurring

427, 668.

14,528/70 glyceride or a condensation product of an alkylene oxide with an organic acid. Compositions of the N-phenylcarbamate compounds formulated in the manner commonly employed in the art for the preparation of microbicidal granules, dusts and aerosols. Practical and presently-preferred embodiments of the present invention are illustratively shown in the following Examples. In these Examples, parts and percent

are by weight. Examples 1 8

To a solution of the dihaloaniline [II] (0.1 mol)

and pyridine (0.12 mol) in toluene (100 the haloformate

[III] (0.1 mol) is added portionwise while stirring, during

which the temperature is maintained at 5 to 15°C. The

resultant mixture is stirred at 20°C for 1 hour. The reac-

tion mixture is washed with cold water and 5 5%hydrochloric acid, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the N-phenylcarbamate compound

Some of the N-phenylcarbamate compounds [I] prepared by the above procedure are shown in Table 1.

-11- 427.6 8

14,52 8/70

0 w

H H H I4~D ct 00 0=0 0--o0 00' p-4 (D 00 0 0 1-0 l 10 0 0- 0 P

0 a ID

0 1

0C

0=O 0=0 I-i 0 I0 0--0 O.jJ 0 0- (D N\) a

N\)

ro0 P -M 0 kjrgi o0

0 L tl1 4 ka

0

a

1-n 01%

0. Ch0

HkH p *\0 CD

12 427. g

414. I 0

-0'

tH a

0 C t

0 0 0-0 "i-4r (D (D 0 0 0 0 0 00 0 0 0< i oC-

00

ol' Ii ll o 0 C a H

c C)mC>

Hj o 00 -o-o-a o- 0-0-0-

0

00

0 0 0 0 0

CDODOD( 00- I-'.I

0 VD 0 P

J ro N1. 0J \Aj CO) .j CD

"n 1-o 0 zHo)

CD 10 1 O

0D -3 ON 0

0o 0 C' -3 -j A I0'

0. '3~0 a%-3

427 6

14,52 8 Examples 9 13 A soultion of the phenylisocyanate [IV] (0.1 mol),

the alcohol (0.1 mol) and pyridine (trace) in isopropyl temperature for 6 ether (100 ml) is allowed to stand at room under reduced hours. The reaction mixture is concentrated pressure to give the N-phenylcarbamate compound prepared Some of the N-phenylcarbamate compounds

by the above procedure are shown in Table 2.

14 4 42.

84 0 %D 0

~D (D F-

0 H C+

0 0 0 ct 0.

0 1

02 HD

0=0 0=0 0=0 0=0C 0 I0 0 I0 I0 P) 1 0-0-C)

(D 0 -0 -4 0 -40 0 P) A) W)

KH HH H H, H- N)CD H- 0..J-N Zs-O cri~ N.D-t .n1 0 0 0 0 n1 0 0 I

OD OD D CD 'AC 0H N) -H

H N) -4,

-4 0

'.0

W H) Nl) N)

15 427l 668

Examples 14 -18

halide LVI] N-phenylCarbamoyl To a solution of the (100 g), J](0.1 mol) in toluene (0.1 mol) .and the alcohol at 5 to pyridinle (0.12 mol) there is dropWise added for 1 and then strrirlg is continued at 2000 while strrinlg, as in Example 1 to The reaction mixture is treated -hour. comfpounld rI]. give the NI-phenylcarbamate compounds 1] prepared Some of the N-phefiylcarbamate are shown in Table 3., by the above procedure

16 6 -421.6 6

1;5 2 PO7

C.+

0 00 130 H 0 00 0C 00c

0

0 IC0 0

I

0 -4 F W* w-

Id :3r H= H 0 H

0 0 Y-- 0

L4 0 \A 0'.%A (0 -~0 -3 0 0 MN) N) U'3 \.n H- H HJ Hl P Hl F H %-9J Hf H- O 0.

0 0 0 00' 0..

%U' 4hj fj

o4 a 0 w 0 C, CL P- 0 0-

0 k0 -11

0-0

I H U' '0

\I1 0~

-4

427. 6 3

14 52 870 Example 19

Preparation of dust:-

The N-phenylcarbamate compound CH,; R2 n-C 3 R3 00002H5 X X' I] (2 parts) and clay (98 par are crushed and mixed well to make a dust containing 2 of the active ingredient. The dust is applicable as such.

Preparation of dust:-

The N-phenylcarbamate compound R1 R 2=CH 3 R CN; X X' C11 (3 parts) and talc (97 parts) are crus

ed and mixed well to make a dust containing 3 of the activ ingredient. The dust is applicable as such.

Preparation of dust:-

The N-phenylcarbamate compound rI: R1 H; R2 CH 3 R3 CONH2; X X'=Cl] parts) and clay (98 parts) arn crushed and mixed well to make a dust containing 2 of the active ingredient. The dust is applicable as such.

Preparation of dust:-

The N-phenylcarbamate comoound rI: R H; R CH,; R CONH2; X X' Br] (2 parts) and clay (98 parts) are crushed and mixed well to make a dust containing 2 of the active ingredient. The dust is applicable as such.

Preparation of wettable powder:- The N-phenylcarbamate compound R1 R2 H; R3 CN; X X' Br] (50 parts), a wettable agent (alkyl- benzenesulfonate) (5 parts) and diatomaceous earth (45 parts

are crushed and mixed well to make a wettable powder contain-

ing 50 t of the active ingredient. The wettable powder -s- diluted with water and then applied.

Preparation of wettable powder:-

The N-phenylcarbamate compound R1 H; R

18 2276 6

145 2 8 H3 R3 COH(CH 3 2 X Cl] (50 parts), a wettable agent

(alkylbenzenesulfonate) (5 parts) and diatomaceous earth parts) are crushed and mixed well to make a wettable powder containing 50 of the active ingredient. The wettable powder is diluted with water and then applied. Preparation of emulsifiable concentrate:- The N-phenylcarbamate compound R1 R2 R

CN; X X' Cl] (10 parts), dimethylsulfoxide (80 parts) and

an emulsifier (polyoxyethylenephenylphenol ether) (10 parts) are mixed well to make an emulsifiable concentrate containing 5 of the active ingredient. The emulsifiable concentrate is diluted with water and then applied. Preparation of emulsifiable concentrate:- The N-phenylc.;rbamate R1 H; R 2 CH3; R

CONHC 3H7 X X' Cl] (10 parts)., dimethylsulfoxide (80 parts) and an emulsifier (polyoxyethylenephenylphenol ether) parts) are mixed well to make an emulsifiable concentrate containing 10 of the active ingredient. The emulsifiable concentrate is diluted with water and then applied. Preparation of granule:- The N-phenylcarbamate compound R1 R2 CH3 R CN; X X' Cl] (5 parts), clay (93.5 parts) and a bind- ing agent (polyvinyl alcohol)(1.5 parts) are crushed and mixed well. The mixture is kneaded with water and granulated to make granules containing 5 5 of the active ingredient. The granules are applicable as such;-- Preparation of granule:- The N-phenylcarbamate compound R1 H; R2 H;

R3 CONH2; X X' C1] (5 parts), clay (93.5 parts) and a binding agent (polyvinyl alcohol) (1.5 parts) are crushed

19 S27.6 Cg

14,528 /7 and granulated to make granules containing 5 of the active ingredient. The granules are applicable as such. Preparation of complex dust:- The 1 -phenylcarbamate compound R1 CH3 R2 CH7; R 3 COOC2H5; X X' Br] (2 parts), O-n-butyl-S- ethyl-S-benzylphosphorodithiolate (1.5 parts) and clay (96.5 parts) are crushed and mixed well to make a dust containing of the active ingredients. The dust is applicable as such. Preparation of complex dust:- The N-phenylcarbamate compound R1 R2 H; R3 GN; X X' C1] (1.4 parts), Kasugamycin (0.1 part), 0,O-dimethyl-O-(3-methyl-4-nitrophenyl)phosphorothioate (2 parts), 3,4-dimethylphenyl-N-methylcarbamate (1.5 parts) and clay (95 parts) are crushed and mixed well to make a dust containing 5 of the active ingredients. The dust is applicable as such. Preparation of complex dust:- The N-phenylcarbamate compound R R2 CH3 .R CN; X X' C1] (2 parts), succinimide (2 parts) and clay (96 parts) are crushed and mixed well to make a dust containing 4 of the active ingre- dients. The dust is applicable as such. Preparation of complex dust:- The N-phenylcgrbamate compound R1 R2 CH; R CN; X X' BrJ (2 parts), zinc ethylenebis(dithiocar- bamate) (1 part), Polyoxin (0.2 part) and clay (96.8 parts) are crushed and mixed well to make a dust containing 3.2 of the active ingredients. The dust is applicable as such. Preparation of complex dust:-

20 42 7.6

14,52 8 The N-phenylcarbamate compound RI H; R 2

CH3 R3 CONM2; X X' Cl1 (2 parts), O-n-butyl-S-ethyl-S-

benzylphosphorodithiolate (1.5 parts) and clay (96.5 parts)

are crushed and mixed well to make a dust containing 3.5 of the active ingredient. The dust is applicable as such.

Preparation of complex dust:-

The T-phenylc-rbamate compound rI: R1 H; R 2 CH3 R3 CONH2; X X' Br] (1.4 parts), Kasugamycin (0.1

part), O,0-dimethyl-0-(3-mcthyl-4-nitrophenyl)phosphorothio-

ate (2 parts), 3,4-dimethylphenyl-N-methylcarbamate

parts) and clay (95 parts) are crushed and mixed well to make

a dust containing 5 of the active ingredient. The dust is applicable as such.

Preparation of complex dust:-

The N-phenylcarbamate compound R H; R 2 CH 3 R, CONH 2 X X' Cl] (2

phenyl)succinimide (2 parts) and clay (96 parts) are crushed

and mixed well to make adust containing 4% of the active ingre-

dient. The dust is applicable as such.

Preparation of complex dust:-

The N-phenylcarbamate compound R H; R 2 CH3 R3 CON(CH 3 2 X X' Cl] (2 parts), zinc athylene-

bis(dithiocarbamate) (1 part),Polyoxin PS (0.2 part) and clay

(96.8 parts) are crushed and mixed well to make a dust contain-

ing 3.2 of the-active ingredient. The dust is applicable as such.

Preparation of complex wettable powder:-

The N-phenylcarbamate compound R1 R2 H; R3 CN; X X' Cl] (15 parts), pentachloronitrobenzene

parts), ,1-(l,l,2,2-tetrachloroethylthio)-4-cyclohexene-

21 427 9, l,2dicarboxyimide (1 at) 45281 1,2dicrboyimde 15 art),diatomaceous earth (45 parts) and a wettable agent (alkylbenzenesulfonate)(5 parts) are crushed and mixed well to make a wettable powder containing 5,of the active ingredients. The wettable powder is dilut- ed with water and theh applied. Preparation of complex wettable powder:- The N-phenylcarbamate compound R CH.~ R2 n-CH; R, COC H parts)- carbamoyl)-2-methoxycarbonylaminobenzimidazol& (10 parts), 6- methyl-2 ,3-quinoxalinedithiol cyclic S ,S-dithiocarbonate parts), a wettable agent (alkylbenzenesififonate) (5 parts) and diatomaceous ekirth (45 parts) are crushed and mix-ed wel'l to make a wattable powder containIng -50 .1of the active ingrc- dients. The wettable powder is diluted with water and then applied. Preparation of complex wettable powder!-' The lipeycraaecompound rI: R1 R2 C.;R 3 C0TNIHBI(0prs, etclrnt X X' Br (3prt)petcornr- benzene (10 parts), ,l,2 ,2-tetrachloroethylthio)-4- cyclohexene-l,2-dicarboxyimide (20 parts), diatomaceous earth (45 parts) and a wettable agent (alkylbenzenesulfonate) parts) are crushed and mixed well to make a wettable powder. containing 50 of the active ing7redient. Preparation of complex wettable powder:-- The -N-phenylcarbarate compound II:_ R1 R2 CH,; R3 C0!H2 X X' Cl] (30 parts), l-(N-n-butylcarba- moyl)-2--methoxycarbonylalninobenzimidazole (lO. parts), 6- methyl-2 ,3-quinoxalinedithiol cyclic S ,S:-dithiocarbonate parts), a wettable agent (alkylbenzenesulfonate) parts) and diatom~aceous earth (45 parts) are crushed and

-22-27 G

14 q- o mixed well to make a wettable powder conaing 50 of the active ingredient. The wettable powder is diluted with water and then applied.

Some of the test results which support the anti- microbial activity of the N-phenylcarbamate compounds are shown below.

Test 1 A dust containing a designed concectration of the test compound(s) was applied to rice plants cultured in field and grown up to the three or four leaved stage at rate of 3 kg per are. After one day, the plants were sprayed to inoculate with a spore suspension of:Pyricularia oryzae thereon. Ten days thereafter, the number of diseased spots was counted. The resutls are shown in Table 4, from which it is seen that the N-phenylcarbamate compounds have stronger antifungal activity than known antifungal agents and, when applied together with known antifungal agents, produce an obvious synergistic effect.

23- 42 76.

1,2 0 Table 4

i est compound Concentration N~umb eroof d-iease N-Phenylcarbamate LI:.

x R, R2 =H;R 3 =CN; X, cI a C5) 2.0 j-14.2 spots Der leaij

F'-Phenylcarbaxnate LI: R, R 2 =CH 3; R 3 16.3 ON; x Ol 1N-Phenylcarbainate LI: R R2 =CH 3 R 2 2.0 12.2 COOC 2H5;X Ci] N-Phenylcarbanate LI: R CH3 R2 C3;2. 19.5 2 51; Brl Nl-Phenylcarbaxnate LI: 1 H; R2= OH3 R 3 2.0 12.3 CONH X X' Cl] N\-Phenylcarbamate LI: R R2 H3 R3 2.0 10.3 OONH2 X XI C1] N-Phenlylcarbamate LI: R H; R2 OH3 R 3 2.0 U-.9 COITH X X' Br] T'-Phenylcarbaxnate LI: l= OH; R 2 n-C3 H7 RL =COOC 2H 5;X X' Br]

0-n-Butyi-S-ethyl-S ben zylphosphorodithio-15 1ate N-Phenyl carbarnate LI: R R2 R 3 =ON -1.4 x X, Ci]

Kasugany ci 1.3 0, 0-Dimethyl-0-( 3- methyl-4-nitrophenyl) phosphorothiolate

3, 4-Dimethyiphenyl N-hmethyl carbamate 1

24 21. 6

14-,5"-j28 70 (continued)

Test compound Concentration Number of diseased soots er leaf N-Ph R,=R 2 =CH 3 R3 ON; X X= C1 1.7

succinimide

;R-=CH CONH2 X-X ci] 0.1 0-n-Butyl-S- ethyl-S..1. ben yjpijL rpdithiolate1. il-Phenylcarbanate L.I: R. 1 R2 CH 3 R3 CON H 2 X X1 Cl ]0

N-(3',51-Dichlorophenyl)-' su ccininilde 0-_n-_Bityi- S- ethyl- 8- bonzylphosphorodithiolate 1.5 33.4

Kasugainycin 38.2 0,O-Dimethyl-0-( 3- methyl-4-nitrophenyl)...010. nhosohorothioate20112 3, 1.5h 106.6T~ .nethycarbamat. 0. N- 3l'5''-Dichloro- 2. Y~hnvi1)succinimi d .04. Non-treated. 83.2

*)Reference compound

25 427.6 G

4,52 8/70 A dust containing a designed concentration of the

test compound was applied to rice plants cultured in pots of

9 cm -in diameter and grown up to the four leaved stage at a

rate of 100 mg per pot by the use of a duster. After one day,

the plants were sprayed to inoculate with a spore suspension

of Cochliobolus miyabeanus thereon. Three day thereafter,

the numnber of diseased spots was counted. The results are

shown in Table 5, from which it is seen that the N-phenyl-

carbamate compounds have stronger antifungal activity

than known antifungal agents.

1, 59(2 7 Table

Test compound Concentration Number of diseas spots Der leaf N-Phenylcarbamate LI: R, =2 R3 CN; 3.0 0 x X' Ci_ N-Phenylcarbamate LI: R1=R 2 CH3 R CN; 3.0 0 x ci N-Phenylcarbanate LI: R,1 =R 2 CH3 R3 ON; 3.0 1.3 X X' Bri N-Phenylcarbanate LI: R 2= CH3 R 3 COOC 2H5 3.0 0.6 x Ci N-Phcnylcarbaiiate 1I: R, CH3 R2 n-C 3H7 3.0 2.6 R= COOC H- X= X' Brl N-Phenylcarbarate II: R= R CH-; R CN; 3.0 2.7 x= X, Il lca lany?,~ ate LI: R1 CH 3 R2 n-C 3H7 3.0 1.9 R -COOC2H5; X X'

N-Phenlcarba.raate LI: R1, R2 H; R3 CN; 3.0 O 9 X V Br_ N-Phenylcarbamate LI: 1 2 H; R CONH2 1.4 -1.3. x x' 3 1-1-Phenylcarba.qate LI: R, H; R2 CH 3 R3 1.4 0.8 CONH 2 x x Ci] ll-Phenylcarbarnate LI: R,1 =R 2 =CH3 R3 COliH 2 1.4 2.3 x X' Ci N-Phenyicarbamate LI: R, H; R2 CH3; R 1.4 4.9 COh 2 X X Br] li-Phenylcarbarnate LI: R, H; R2 CH 3 R3 1.4 2.1 CO(CH02; X= X'=CI] -Phenylcarb7ma-e LI: R 2 CH 3 R 1.4 0.8 7 X= X' C1I

a21.6I,

14,52 8 (continued) STest compound Concentration Number of disease s ots Der leaf N-Phenylcarbamate I: R1 H; R2 CH R 1.4 CONH2; X X' Br]

Kasugamycin 0.1 0 O, 0-Dimethyl-0-( 3-methyl- 4-nitrophenyl)phosphoro- 2 thioate

3,4-Dimethylphenyl-N- methlc rb te Ksr cm 0.1 2.8 0, 0-Dim ethyl-0- 3-methyl- 4-nitrophenyl)phosphoro- 2.0 thioate 50.3 3,4-Dimethylphenyl-N- .netIhvlarba te 1.5 51.2 Ion-treated 72.3 Reference compound Test 3

A dust containing a designed concentration of the test compound was applied to rice plants grown up to 50 to cm tall in Wagner pots of 1/5000 are at a rate of 3 kg per are by the use of a duster. After one day, a mycelium-disc- inoculum of Pellicularia Ssakii was inoculated on the sheath. The infectious state at the sheath was observed 5 days there- after, and the degree of damage was calculated according to the following equation:

\7 Infection Number of Degree of damage Z index- Total number x 100 of stems x 3

wherein the infection index was determined on the following. criteria: 1JdiLAL Infection index Infectious Infectious t state 0 No infectious spots on sheath

14, 5 2 8 1 Infectious spot-like parts

2 Infectious spots of less than

3 cm in size

3 Infectious spots of not less

than 3 cm in size

The results are shown in Table 6, from which it is seen that

the N-phenylcarbamate compounds have stronger antifungal

activity than known antifungal agents and, when applied

together with known antifungal agents, produce a synergistic

effect.

Table 6 14,2

Test compound Concentr, Degree of' heffih Lcal ti on jF) 1damage in 1 a- N-Pheirlycarbamate LI.: R =-R 2 H; R3 CN; x I' C-il N-Phenylcarbamate R=R2 CH3 R3 CN; 3.0 9.4 x X' ci* 3_ N-Phenylcarbanate LI: R,=R2 CH3; R3 CN; 3.0 10.3 X X, Br N- 2 henylcarbamate I- R2 CH3 R3 3.0 9.1 COOCH 5 X X, Cl] N-Phenylcarbamate LI: R= R CH R3 CN; X =X Br]

Zinc ethylenebis- 1 0 (dithiocarbamate)

Polo xin 0.2 Zinc ethylonebis- (dithiocarbamate) 1.0 100 Polyoxin 0.2 39.7 c-Cyancethyl N-(2,4,5- trichilorophenyl)- 3.0 100 carbamate Non-treated 100

Reference compound. Test 4

A wettable-pbwder containing a designed corloentra- tion of the test compound was.applied to rice plants Emwn up-to 50 to 60 cm tall in Wagner pots of 1/5000 axe ati a rate of 3 kg per 10 are by the use of a duster. Aft0P one day, a mycelium-disc-inoculum of Pelliculgria sasakii was inoculated on the sheath. The infectious state at th@ sheath was observed 5 days thereafter, and the degre@ Of damage was calculated according to the following equation:

30 2t66 8

14 2 8/70 SInfection Number of Degree of damage Total nber s x 100 of stems x 3

wherein the infection index was determined on the following

criteria:

Infection index Infectious state

0 No infectious spots on sheath

1 Infectious spot-like parts

2 Infectious spots of less than

3 cm in size 3 Infectious spots of not less

than 3 cm in size The results are shown in Table 7, from which it is seen that the N-phenylcarbamate compounds have stronger antifungal activity than known antifungal agents and, when applied together with known antifungal agents, produce a synergistic effect.

31 427.6 68

Tabl e 7

Concentration I Degree-.of Test compound Cfdamae N-.Pheylcarbaate 3. R -ItH; R .500

CONfi X X V Cl] 'i-.Pheriylcarbamfate LI R H;R 2 =CH 3 ;R 3 500 COMH 2 X' C11] N-Phenylcarbamate L: R 500 5.1 R =R =0CH CONH X X= Ci] N-~Phenycarb:1a iiatei R H; R 2 =CH 3 R 3 5004. CONH 2 X X' =B r] N-Phenylcarbamate I: 5.2 R= H;9 R2 CH 3 R3 =500

cC 3 2 X Cl] 2-Phenyl carb amat R,: C 3 R1 COM0 500 1.1 2 CH-C 3 X X' Cl a-Carbarnoyleth 500 100 ~ihloro henl 1 carb ate

*)Reference compound Test wal A wettable'powder containing the test compound and diluted with water to make a designed concentration pots of 12 cm in applied to pumokinf seedlings cultured in leaved stage at diameter and grown up to the three or four pot. After one day, the a rate of 7 ml of the dilution per suspension of plants were sprayed to inoculate with a spore Sphpe'roiheca fuligine~ thereon. Ten days thereafter, the four leaves, and infectious state was observed on the upper infectious are the degree of damage was *c'alculated from the according to the following equation:

-32 42,6

14,52 8 Number of S (Infection index v lave CIU ~V I Degree of damage Total number x 100 of leaves x

wherein the infection index was determined on the following

criteria:

Infection index Infectious area

0 None 1 Small 3 Medium

Large The results are shown in Table 8, from which it is seen that the N-phenylcarbamate compounds have stronger antifungal activity than known "antifungal agents and, when applied together with known antimicrobial agents, produce an obvious synergistic effect.

Table 8

Test compound Concentration Degree d N-Phenylcarbamat e R2 H; R3 CN; 1,000 10.3 X X' C11 N-Phenylcarbamate [I: 1 R2 CH3 R CN; 1,000 15.6 X X' Br t 4 4 N-Phenylcarbamate [I; 7 R1 R2 R 1,000 13.8 COOC2H; -X X' C0] N-Phenylcarbamate [I; T 1 CH3 R2 n-C3H7; 1,000 20.4 R1 COOCH; X X' I] N-Phenylcarbamate I: H; R2 CH R CONH 1,000 6.8 X X' Cl N-Phenylcarbamate R= R2 CH R CONH 2 X 1,000 7.3 Cli

t3. a 7.6 68

%1452 170 (continued)

Reference compound

Test 6

In each pot of 9 cm in diameter, there was charge

field soil, and soil (10 ml) infected with Pelliculari The test filamentosa was dispersed over the surface. with compound in emulsifiable concentrate form was diluted and the dilution was water to make a 500 ppm concentration, 15 ml per pot. After poured into the said pot at a rate of therein. Five two hours, 10 seeds of cucumber were sowed

days thereafter, the infectious state of the grown seedling

34 427.6 68

1452 8 was observed, and the percentage of stand was calculated

according to the following equation: Nuber of healthy seedlings in treated plot x 10 0 Percentage of stand Niumber of gemination uber of germination in untreated plot The results are shown in Table 9, from which it is seen that the N-phenylcarbamate compounds have stronger

antifungal activity than known antifungal agents.

o

35 427. 6 68

.14~52 870 Table 9

Pceentage Test copudConcentration compund(ppm) of stand

N-~Phenylcarbamlate ri: R H; R3= CN; 500 89.4 xX CLL N-Phenylcarbarniate LI: R R2 OH 3 R3 ON; 500 92.3. x X- Cl NIPhenylcarbamate II: R1 R2 OH3 R 3 CN; 500 83.2

4-Phenylcarbamlate I. R 1 R 2 =CH3 ;R 3 500 99.0 0000 H 5;X X' C11 N-Phenylcarbamate LI: R= OH3 R2 =n-C 3 H7 500 74.8 R COOC H X=XV Br] N-Phenylcarb ama te I

RR ,H R=CH; 508.

N-~Pheylcarbarnate I- H;R 2 H;R= C; 3 =ON 500 93.4

-JPhenyc~rbamate -I R H; R=COH 2 500 95.6 x x=Cil X=

11-Phenylcarbamlate RjH; R OH3 CH R COH; 500 9.4 CO();X X Cl INPhenycarbamate _1: R- C R3- ON2 500 9.8

carbamatlrbae '-I H; IramlthH- 3,4-di-. 500 4.2

chir henl carbamate

427. 6 6

14,52 8/7Q (Continued) Test compound Concentration Percentage (ppm) of.stand Pentachloronitrobenzene 500 83.4 Non-trented (uninoculated) 100 Non-treated (inoculated) 0

Reference compound

Test 7

When determined according to the agar dilution

method, the N-phenylcarbamate compounds afforded minimum inhibitory concentrations as shown in Table 10 against

Aspergillus niger ATCC No. 9642 which causes serious damage to industrial products.

Table

Test compound Minimum inhibitory concentration (ppm) N-Phenylcarbamate R R2 H; R 3 CN; X X' C1] 2,000

N-Phenylcarbamate R1 R2 CH3 R3 CN; X X' Cl] 2,000

N-Phenylcarbamate R CH R 2 =n-C3 7 R3 COOC 2 H 5 5,000 X X' Br]

37 427 668

Claims (1)

14,528 The claims defining the invention are as follows;-

comprising an effective amount 1. A composition

of the N-phenylcarbamate compound of the formula: X R

S -NH-C-0-C-R 2 7 X 0 R3

wherein R1 and R2 are each hydrogen or lower alkyl, R3 or is cyano, carboxyl or a group of the formula: -COOR 4 -CON 5 wherein R4 is lower alkyl and R5 and R6 are each R6 hydrogen or lower alkyl and X and X' are each halogen, or provided that R1 and R 2 are both hydrogen or same different lower alkyl when R is cyano and that R1 and R2

are each lower alkyl when R 3 is carboxyl or the group of above, and an the formula: -C0R4 wherein R 4 is as defined

inert carrier.

A composition according to claim 1, wherein. 2.

R and R are each hydrogen or methyl.

3. A composition according to claim 1, wherein

R 3 is cyano or a group of the formula: -COOCH 3 or -COOC 2 H5

4. A composition according to claim 1, wherein

the N-phenylcarbamate compound is of the formula:

x CH

S NK-C-O-C-CH

.0 I R

14, 52 8/170 wherein R3is cyano or ethoxycarbonyl and X and X' are. each chlorine or bromine.

A use of the composition as claimed in any one of claims 1 to 4Jas a microbicide In the treatment of'disease conditions, except in the treatment of said conditions in man.

6. An N-phenylcarbmte compound of the formula

14,52 8 X

NH-C-O-C-R 2

So R3

wherein R1 and R2 are each hydrogen or lower alkyl, R is

cyano, carboxyl or a group of the formula: -COOR or -CONR Rg wherein R4 is lower alkyl and R 5 and R6 are each hydrogen

or lower alkyl and X and'X' are each halogen, provided that

X and X' are not simultaneously chlorine when R is cyano,

that R1 and R2 are each lower alkyl and X and X' are not

simultaneously chlorine when. R is a group of the formula:

-COOR wherein R is as defined above and that R1 and R 2 are

each lower alkyl when R3 is carboxyl.

7. An N-phenylcarbamate compound according to

claim 6, wherein the compound is of the formula:

Br Ri 0 v-C--C -C-R 11 1 2 r 0 COOR4 Br

wherein R1 and R2 are both hydrogen or methyl and R4 is as

defined in claim 6.

8. An N-phenylcarbamate compound according to

claim 6, wherein the compound is of the formula:

X

I- 12" NH-C-0-C-R 0 CONH 2

wherein R and R 2 are each hydrogen or methyl and X and X'

are as defined in claim 6. 9. A process for preparation of the N-phenylcarba-

S. 42 .6 63 mate compound as claimed in claim 6, which comprises reacting a dihaloaniline of the formula: x XNH2 xv- X' wherein X and X' are each as defined in claim 6 with a halo- formate of the formula: R .1 X"-CO-C-R- tI I wherein X" is halogen and R, R2 and R are each as defined react- in claim 6 in the presence of an. acid-eliminating agent, ing a phenylisocyanate of the formula:. x

X1. NCO

XI

wherein X and X' are each as defined in claim 6 with an alcohol

of the formula:

Rl HO-R

R3

wherein Rl, R2 'and R3 are each as defined in claim 6 or react-

ing an N-phenylcarbamoyl halide of the formula: x HC- X" X1 0 H._II. 0 X'

are each as defined in claim 6 and X" is as wherein X and X' 4 427. 6 68

1,5 2 8 defined above with the said alcohol in the presence of an acid-eliminating agent.

A method for preparation of an antimicrobial composition which comprises admixing at least one of the N-phenylcarbamate compounds as defined in claim 1 with an inert carrier.

11. A use of the N-phenylcarbamate compound as defined in claim 1 as an antimicrobial agent in the treatment of disease conditions, except in the treatment of such conditions in man.

12. A method for controlling the growth of micro- organisms in the treatment of animals excluding man which comprises applying at least one of the N-phenylcarbamate compounds as defined in claim 1 to the micro-organisms.

13. A method for controlling the growth of plyto- pathogenic fungis in the treatment of disease conditions, except in the treatment of such conditions in man.

DATED THIS 29TH DAY OF APRIL, 1970 SUMITOMO CHEMICAL CO., LTD. By its Patent Attorney,

A. WALLACE SMITH

42 427.6 6 8