PH26182A - Intermediate compounds for biocidal imidazole compounds - Google Patents

Description

CL. ® a oo - - ' ct ; ’ ‘ ~~ vr i i . | 2618: (J vo J Ae a .

PEER ke 2 ATE SME a ei Beptenal TAEAZaLE CEhfouin hs

FIELD OF THE INVENTION rr

The present invention relates to novel imidazole g < » DD compounds and biocidal compositions compris 4 the Bsame SE m O for controlling harmful organisms. w = 2 < © he No = 52

BACKGROUND OF THE INVENTION ~N = © 37

Imidazole type compounds proposed {so far are k%

Bu: exemplified below. : no =X . Belgian Patent 852313 (published Sept. 12, 1977) discloses (4,5)-dichloro-imidazole(2)-carboxylic acid

Cl derivatives having the formula XVYZC 47 wherein CXYZ

N cl

H represents a C atom with 3 bonds attached to hetero atoms, and Japanese Patent publication No. 15625/85 (published

Apr. 20, 1985) discloses the following reaction scheme, c1 =~ —

CCl, > CCl, ’ — NT oo Cl N c1 Cl while no compound having other substituents than chlorine atoms at the 4 and 5-positions in the imidazole ring and - having a substituted sulfonyl group in the imidazole ring : is disclosed in both of the above references. ) BAD ORIGINAL _ &

Recl. Trav. Chim. Pays—Bas » 1973, 92(3), 449-59 » phenyl pa phenyl discloses we J ' ne 1 , etc.;

N H N phenyl

H H

DT-0S 2317453 (published Oct. 11, 1973) discloses 2 CN » CN guaternary ammonium salts of we I or 4 J

N CN N CN

H H etc.; J. Org. Chem., Vol. 44, No. 16, 1979, 2902-2906

Pa R discloses we 1 (R: H, CH3), etc.; EP 31086

N

H

HF X

(published July 1, 1981) discloses rn J (R': —-CQZR,

N Y

H

CN); J. Org. Chem., vol. 51, No. 10, 1986, 1891-1894 discloses 2-cyano imidazole, etc.; ‘and Research

J IE

_ pisclosure, June (1986), 323-324 (C.A., 106, 49942e) : » phenyl-X : discloses ne J , etc.; while no

N phenyl-X'

H compound having a substituted sulfonyl group in the imidazole ring is disclosed in any of the above-described references. ! Japanese patent Application (OPI) No. 4303/80 : (published Jan. 12, 1980) (the term nopI" as used herein ’ &

CN oh ] N _ 9 -

BIE ALS a means a "published unexamined patent application") discloses 1-(N,N-dimethyl-

S0,N(CH3)

N CN sulfamoyl)-4,5-dicyanoimidazole 4 I ; C.A., 95:

N CN

7283q [Japanese Patent Application (OPI) No. 157570/80 (published Dec. 8, 1980)] discloses sulfamoylimidazole

SO,N(CH3) SON (CH),

N~— CN N — CONH, derivatives of 4 J and 4 J ; C.A., 101:

N CONH,, N CN 7092u (J.Chem. Soc., Perkin Trans. 1, 1984, (3), 481-6)

N—¢ Li discloses ny , etc.; and C.A., 106: 138324x yo . N (Tetrahedron, 1986, 42(8), 2351-8) discloses

S0,N(CH3)

Li

Essig | , etc.; while no compounds having other

N than a hydrogen atom, a lithium atom, or an —-Si(Et)3 group at the 2-position in the imidazole ring as a substituent are disclosed.

Japanese Patent Application (OPI) No. 142164/87 (published June 25, 1987) discloses 4,5-dichloro-imidazole . N Cl . compounds having the formula r, I , while no

N Cl

SO,NR|R, — 3 —_

— oo EE — - compounds having other substituents than Chlorine atoms at the 4 and s-positions in the imidazole ring are disclosed.

References listed below disclose imidazopyridine compounds and/or benzimidazole compounds in which the compounds contain a condensed ring of an imidazole ring with a benzene ring and/or a pyridine ring in their chemical structures.

U.S. Patert 3609157 (issued Sept. 28, 1971)

U.S. Patent 3681369 (issued Aug. 1, 1972) _ Belgian patent 830719 (published Dec. 29, 1977)

Belgian Patent 845641 (published Feb. 28, 1977)

U.S. Patent 4536502 (issued Aug. 20, 1985)

U.S. Patent 4579853 (issued Apr. 1, 1986)

French Patent 2559150 (published Aug. 9, 1985)

Japanese patent Application (OPI) No. 103873/86 (published May 22, 1086)

Japanese patent Application (OPI) No. 22782/87 (published Jan. 30, 1987)

EP 219192 (published Apr. 22, 1987)

Japanese Patent Application (OP1) No. 195379/87 : (published Aug. 28, 1987)

EP 239508 (published Sept. 30, 1987)

SUMMARY OF THE INVENTION

An object of the present invention is to provide imidazole compounds of the following .general formula (I) and biocidal compositions comprising the same for controlling harmful organisms:

” — ] ;

R,

Ry - : I (1)

A,

SO,R, wherein: :

Ry represents a cyano group or a -CSNHRs group, wherein Rs represents a hydrogen atom, a Ci—a alkyl group, or a —CORg group: wherein Rg represents a Ci-4 alkyl group, a halogenated Ci-a alkyl group, or a phenyl group;

R, and Rj each represents a hydrogen atom; a halogen atom; a nitro group; a cyano group; a ‘trimeth- ylsilyl group; a Ci-6 cycloalkyl group; a naphthyl group; | a Ci-12 ‘alkyl group which is optionally substituted with one or more halogen atoms, hydroxyl ° groups, acetoxy groups, Ci-4 alkoxy groups, halogenated : Ci-4 alkoxy groups. phenyl groups. halogenated phenyl groups, Or Ci-a alkylated phenyl groups; a Cg-10 alkenyl group which is optionally substituted with one or more halogen atoms; a Cy-g alkoxy gfoup which is optionally : substituted with one Or more halogen atoms; a phenyl group which is optionally substituted with one or more halogen atoms, C1-4 alkyl groups, halogenated Cioa alkyl groups, Ci-4 alkoxy groups, halogenated Ci-4 alkoxy groups, " Cy-a alkylthio groups, halogenated Ci-4 alkylthio groups, nitro groups, cyano groups, Or 3,4-methylenedioxy groups;

sd i a furyl group which is optionally substituted with one or more halogen atoms or Ci-4 alkyl groups; a thienyl group which is optionally substituted with one or more halogen atoms or Cj-4 alkyl groups; a pyridyl group which is optionally substituted with one or more halogen atoms or

Ci-4 alkyl groups; an -S0,R7 group, wherein Ry represents a Cj-g alkyl group, a Cp. alkenyl group, a phenyl group which is optionally substituted with one or more halogen atoms, a benzyl group, a pyridyl group which is optionally substituted. with one or more halogen atoms, Ci-4 alkyl groups, Or halogenated Ci-4 alkyl groups; or an -NRgRg group, wherein Rg and Rg each represents a Ci-a alkyl group, and n is 0, 1, or 2; or a -CO(NH)pRyp group, wherein Rjg represents a Ci-g alkyl group which is optionally substituted with one or more halogen atoms, a

Cy1-4 alkoxy group which is optionally substituted with one or more halogen atoms, or a phenyl group which is optionally substituted with one or more halogen atoms; and m is 0 or 1; and

Ry represents a Ci-s¢ alkyl group which is optionally substituted with one or more halogen atoms; a

C3-g cycloalkyl group; a phenyl group; a thienyl group; or an -NRjiRj2 group, wherein Rj; and Rj each represents a hydrogen atom, a Ci-4 alkyl group which is optionally " substituted with one or more halogen atoms, a Cz-4 alkenyl group, Or Rj and Rj; are combined with each other. - 6 -

B .

porn > . together with a nitrogen atom adjacent thereto to form a pyrrolidinyl group, a piperidinyl group, a morpholino group, or a thiomorpholino group, provided that Rj;; and

Ry2 are not simultaneously a hydrogen atom; provided that R, and R; are not simultaneously a halogen atom.

Another object of the present invention is to provide a process for preparing the imidazole compounds of : the formula (I) hereinabove. . A further object of the present invention is to provide intermediate compounds of the following general formula (II'): ~ . R, ed (I1') wherein Rz and R,; each represents a hydrogen atom; a halogen atom; a nitro group; a cyano group; a trimeth- ylsilyl group; a Cj. cycloalkyl group; a naphthyl group; a Cj-12 alkyl group which is optionally substituted with one or more halogen atoms, hydroxyl groups, acetoxy groups, Ci-4 alkoxy groups, halogenated

Ci-a alkoxy groups, phenyl groups, halogenated phenyl groups, or C;-4 alkylated phenyl groups; a Cz-10 alkenyl group which is optionally substituted with one or more

- — rr halogen atoms; a Cj-g alkoxy group which is optionally substituted with one or more halogen atoms; a phenyl group which is optionally substituted with one or more halogen atoms, Ci-4 alkyl groups, halogenated Cj;-4 alkyl groups, Cji-4 alkoxy groups, halogenated Cj;.4 alkoxy groups,

Cy-4 alkylthio groups, halogenated Cj-3 alkylthio groups, nitro groups, cyano groups, Or 3,4-methylenedioxy groups; a furyl group which is optionally substituted with one or more halogen atoms or Cji-4 alkyl groups; a thienyl group which is optionally substituted with one or more halogen atoms or Cji-g4 alkyl groups; a pyridyl group which is optionally substituted with one or more halogen atoms or

C3-4 alkyl groups; an -SOhR7 group, wherein Ry represents a Cj-g alkyl group, a Cz-g alkenyl group, a phenyl group which is optionally substituted with one or more halogen atoms, a benzyl group, a pyridyl group which is optionally substituted with one or more halogen atoms, Cj-4 alkyl groups, or halogenated Ci-4 alkyl groups; or an -NRgRg group, wherein Rg and Rg each represents a Cj3-s4 alkyl . group, and n is 0, 1, or 2; or a -CO(NH)pR1p group, : wherein R;p represents a Cjy-4 alkyl group which is optionally substituted with one or more halogen atoms, a

Ci1-4 alkoxy group which is optionally substituted with one . ~~ or more halogen atoms, or a phenyl group which is "optionally substituted with ‘one or more halogen atoms; and m is 0 or 1, - 8g -

- - _— provided that compounds represented by the following general formula (II"):

Ry wd (1I") wherein R,' and Ry’ are simultaneously a hydrogen “atom, a halogen atom, a cyano group, or a phenyl group which is optionally substituted with same or different C, , alkoxy group or c, alkylthio group at the para-position; and wherein R,' is a hydrogen atom and R,' is a methyl group or a phenyl group, are exzluded.

Among the imidazole compounds represented by the general formula (I), preferred compounds of the present invention are illustrated below.

Compounds of the general formula (I) wherein R; is a cyano group;

Compounds of the general formula (I) wherein R, and R, each represents a hydrogen atom; a halogen atom; a nitro group; a cyano group; a Cy-12 alkyl group which is optionally substituted with one or more halogen atoms, hydroxyl groups, Ci-4 alkoxy groups, phenyl groups, _ halogenated phenyl groups, or Ci-3 alkylated phenyl groups; a Cp-10 alkenyl group which is optionally substituted with one or more halogen atoms; a phenyl - 9 - Bh ne > group which is o6ptionally substituted with one or more halogen atoms, Cj;-4 alkyl groups, Ci1-4 alkoxy groups, halogenated Cj-4 alkoxy groups or nitro groups; an —SOpRy group, wherein R; represents a Cj-¢ alkyl group, a phenyl group which is optionally substituted with one or more halogen atoms; or an -NRgRg group, wherein Rg and Rg each represents a Ci-4 alkyl group, and n is 0, 1, or 2; or a —CONHR10 group, wherein Rjp represents a phenyl group which is optionally substituted with one or more halogen atoms, . provided that R, and R; are not simultaneously a halogen atom; : Compounds of the general formula (I) wherein R, is a Cy ¢ alkyl group or an -NR,;R;, group, wherein R,; and R,, each represents a C,_, alkyl group;

Compounds of the general formula (I) wherein R, is a hydrogen atom; a Cj-12 alkyl group which is optionally substituted with one or more halogen atoms, phenyl groups, or halogenated phenyl groups; a C3-4 alkenyl group; a phenyl group which is optionally substituted with one or . more halogen atoms, Cjy-4 alkyl groups, Cj-4 alkoxy groups, or halogenated Cj-4 alkoxy groups; a C,_¢ alkylthio group: or a phenylthio group which is optionally substituted with one or more halogen atoms;

Compounds of the general formula (I) wherein Rj is a hydrogen atom, a halogen atom, or a cyano group;

. o

Compounds of the general formula (I) wherein R, is an -N(CHj), group;

Compounds of the general formula (I) wherein R, is a Cy-12 alkyl group which is optionally substituted with one or moré halogen atoms, phenyl groups, Or halogenated phenyl groups; a Cz-4 alkenyl group; a phenyl group which is optionally substituted with one or more halogen atoms; or a Cy-g alkylthio group;

Compounds of the general formula (I) wherein’R, is a halogen atom; and

Compounds of the general formula (I) wherein R, represents a cyano group; R, represents a Ci-12 alkyl group or a phenyl group; R; represents a chlorine atom; and R, represents an -N(CH4), group.

DETAILED DESCRIPTION OF THE INVENTION

In the general formula (I) described above, definitions of C,_4 alkyl group and alkyl moieties of C;_, alkoxy group and C,_, alkylthio group may include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl . and tert-butyl groups. Definition of C, ¢ alkyl group may include n-pentyl and n-hexyl groups in addition to the exemplified C,_, alkyl groups hereinabove. Definition of

Cy.32 alkyl group may include heptyl, octyl, nonyl, and decyl groups in addition to the exemplified C;_g alkyl groups hereinabove. Definition of Cj ¢ cycloalkyl group may include cyclopropyl, cyclobutyl, cyclopentyl, and

[ cyclohexyl groups. Definition of C,_, alkenyl group may include an allyl group, etc. Definition of C,_g alkenyl group may include a pentenyl group, etc. in addition to the exemplified CC, , alkenyl groups hereinabove.

Definition of C,_;, alkenyl group may include a geranyl group, etc. in addition to the exemplified C,_ alkenyl groups hereinabove. Definition of halogen atom may include chlorine, bromine, fluorine, and iodine atoms. ban !

The novel imidazole compound represented by the general formula (I) described above can be prepared specifically by the following process: [A]

J)

Ry I + Y-SO,R,

N Rj

H (III) (11) : - - R, to 150°C i a Ry Ni 1 to 48 hours N R,4

SO,R, (1) . wherein R,;, R,, Ry, and R, have the same meanings as described above; and Y is a halogen atom.

In the general formula (I) described above, compounds wherein R; is a cyano group can also be prepared by the following process: - 13 - ears

MA a . a ]

R

! R, /. 2 74 Step-1 Ne —. nC © «

N Y-SO,R, (III) N

H 10 to 150°C SO,R, 1 to 48 hours (11-1) (1-1)

Step—2

R; n-C4HoLi/tetrahydrofuran J

Ry-1 N R, -80 to 30°C J 1 to 24 hours SO,R, (1-2)

In the general formula (1-2) described above wherein R; is an -SR, group, R,SSR, can also be used instead of Ry-I _n Step-2 of the process (B] described above. In the foregoing formulae, R,, Rj, Rss Ry, and Y have the same meanings as described above. . In the general formula (I) described above, © compounds wherein R,; is a cyano group, and R4 is a " hydrogen atom, a chlorine atom, or a bromine atom can also be prepared by the following process:

zc . ae ed (cl ’ 72h ”" R "

Ry Step-1 2 wl we . a Y-SO,R, (I.I) N Ry"

H 3 10 to 150°C 1 to 48 hours (11-2) (1-3)

SOR

- - Step-—-2 | 274 i R, n-CaHgLi/tetrahydrofuran

Ry-¥' - N Ry" ~-80 to 30°C 1 to 24 hours (1-4)

In the general formula (I-4) described above wherein R, is an -SR, group, R,SSR, can also be used . instead of R,-¥' in Step-2 of the process [C] described - above; and wherein R, is a -CH(OH)-R,, group (wherein Ry, is an alkyl group or an optionally substituted phenyl group), R;;-CHO can also be used instead of R,-Y' in Step- 2 of the process [C] described above. In the foregoing formulae, R,y Ruy and R, have the same meanings as " described above; R," and Ry" are simultaneously a —_ 15 -—

TT hydrogen atom, a chlorine atom or a bromine atom; and y! is a chlorine atom, a bromine atom, or a iodine atom.

In the general formula (I) described above, compounds wherein R; is a -CSNH, group Or a —~CSNHCOR¢ group can also be prepared by the following process: (D] ‘ R

R2 Step-1 2

NC / 1 > XC &

Y-SO,R, (III ) i R; 10° te \ N Rs

H o 150°C 1 to 48 hours SO,R,

Step-2

H c I Ra 2 I

J H,NC os dioxane, triethylamine N Ry to 70°C SO.R } 0.1 to 5 hours 274 : (1-6) . —_ 16 .-

Pe © Step-3

Recoc 0 i / Tr - RgCHNC 7 acetone, pyridine Lg Rg °

Et hours S02R, (I-7) wherein R,, Rj, R;, Rg, and Y have the same meanings as’ described above. * The process [A] and Step-1 of the processes [B] through [D] described above are carried out, if necessary and desired, in the presence of a solvent and an acid ’ acceptor. : Examples of the solvent include aromatic hydrocarbons such as benzene, toluene, xylene, chloro- benzene, etc.; cyclic or acyclic aliphatic hydrocarbons such as chloroform, carbon tetrachloride, methylene chloride, dichloroethane, trichloroethane, n-hexane, cyclohexane, etc.; ethers such as diethyl ether, dioxane, ' tetrahydrofuran, etc.; ketones such as acetone, methyl : ethyl ketone, methyl isobutyl ketone, etc.; nitriles such : as acetonitrile, propionitrile, etc.; and aprotic polar solvents such as dimethylformamide, N-methylpyrrolidone, : dimethyl sulfoxide, sulfolane, etc.

As the acid acceptor, any of inorganic bases and organic bases can be used. Examples of the inorganic base

_ oo include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, etc. ; alkali metal or alkaline earth metal carbcnates such as anhydrous potassium carbonate, anhydrous calcium carbonate, etc.; alkali metal hydrides such as sodium hydride; alkali metals such as metallic sodium; etc. Further, as the organic base, metion may be made of triethylamine, etc.

The reaction described above can be carried out in the presence of a suitable catalyst. As the catalyst, mention may be made of, for example, a phase transfer catalyst such as a quaternary ammonium derivative.

As the halongen atom shown by Y in the general formula (III) described above, mention may be made of a chlorine atom, a bromine atom, an iodine atom, and a fluorine atom; of these, preferred is a chlorine atom.

In the reaction scheme described above, the compounds represented by the general formula (III) are known compounds, and the compounds represented by the general formula (II) can be prepared by either one of the following processes. (1) . R, R, ! I C1SO,R, / J

N R, K2CO3s CHyCN N R,

H 10 to 150°C 1 to 48 hours SOR, . . - 18 - . .

Ha. AREA a a mene Co . Co Cp mE at ed Co

~ n-C,HgLi, R.NCS 1 / Ry

J Rg NHC 3 tetrahydrofuran N ~80 to 30°C Rj 1 to 24 hours SO,R,

HC1 I R, — R NHC / 50 to 100°C 1 to 12 hours o R, (2) - a: n-C,HyLi 0 R / 2 dimethyl formamide I / 2 3 | -_— HC <

N R, tetrahydrofuran N R, . : -80 to 30°C

SOR, 1 to 24 hours SO,R, . . R,

NH,OH-HC1 / > HON=CH—". pyridine N R 50 to 150°C 3 1 to 24 hours SO,R, : R, acetic anhydride ’ _— NC 7 pyridine 50 to 150°C a Ry 1 to 24 hours

H,S : R,

J] triethylamine i pyridine N Ry to 70°C H 0.1 to 5 hours _ 19 —

. yo. ele

B (3)

R, R,

J C1CH,0C,H,Si(CH;y), /: —r

N R, dimethylformamide N R,

H NaH, 10 to 70°C 1 to 12 hours CH,0C,H,Si(CH;),

Ry

C1CN, CH4CN / HCl : - > NC o | —_— -30 to 70°C N 50 to 100°C 1 to 12 hours Ry 1 to 12 hours

CH,0C,H,Si (CH;) 4

Rj

N R

3

H

. (4)

Ry halogenating agent Ry ne— | — ne -50 to 100°C

N 1 to 24 hours N Y

H H

: (5)

R

R 2

J 2 Y-SO,R, /

NC | —_— NC to 150°C N

N 1 to 48 hours

H SO,R, — 20 —_

N . R n-C,HqLi, Ry-1I J 2 HCl water

Ti wed Ee tetrahydrofuran 30 to 100°C -80 to 30°C N Rj 0.5 to 2 hours 1 to 24 hours

SO,R,

R,

N R

H 3 (6) }

R

R2 NH, OH 2 74 x || ——— x to 120°C N . N R, 1 to 60 hours Rj

H Se H (7)

PE oo

Ra R (CH,0) ,CHC -HC1 3 2

AV ’ Nock, CH30 R, more — In

CH,0H, 0 to 70°C /

C,H50 NH, 146 12 hours CH,0 o R, (i) HCl (ii) NH20H.HC1/pyridine R, (iii)acetic anhydride y

NC } - > 50 to 150°C ” R 1 to 24 hours H 3

0 R ¢ Ry NH,OH I 2 ahd | ———— ae 50 to 150°C N

N Rj 1 to 100 hours R3

N H

. R, , POC, J -——— NC 50 to 110°C 1 to 12 hours o Rs (9 0 R c / Ry R NH, Wi; ? ——

CH,0C RgNH 0 to 150°C N

N R, 1 to 50 hours R3 u H

S

S I | I 8 RsNH toluene N Rj

H

(10)

R

R 2 / 2 NH,/0, J -— > NC - . N

N 4

3 R R, 2 / Z K2S,04 J : CH, | —————> HOCH, y N N

H H

0 R, R,

MnO, I J NH,OH- HC1 J

ML dg eed)

N N

H H

. . R, acetic anhydride J — > NC

N

H

(12)

R, . R,

J Cl,/HC1 = HC1

CH, | — ee Cl,C = . _—

N Nel

H

R R

2 2 : J NH, OH J cel, | xe

N Cl N cl

H H

- = (13)

R, R, / I 0-Y eT NaCN ———— .

N 0 N electrode reaction

H

Rz R, (i acid or alkali

A lil g N N lL H (14)

R, . R . halogenating agent / 2 / n-C,HyLi /: | CuCN

Y os >

Q N Q N

R

2 2 . Y R, ne—< acid or alkali J . _ NC g N .

H ge (15) cacooma 0 R "Cafe [2 2 acid or alkali

TS

N

Q

R

I 2 (i) SOC1,/(ii) NH,OH

N

- N-

POCly or soci, = gl

N

H

(16) e, / | (CH20) / ~

S — » HOCH,—<., . oN

Q

0 )

HC— | ~~ 5» HON=C /

Q N

R, acetic acid or alkali HON=CH— // | anhydride ee rrr - >

N

H

R,

N

H

(17)

R . “2 dimethylformamide | : R, a n-C,HgLi we L- J 2 -— NZ,

Q N° o NM

R,

NH,OH-HCl / acid or alkali or, HON=CH—

Q N

R, acetic R

J anhydride 2

HON=CH | — x /

N N

H H a

R, R / | Na/NH, J 2 MnO,

HOCH, ———— HOCH, | —_—

H

R, acetic

NH,OH-HC1 J anhydride —_— HON=CH | >

N

H

Ry ” 1 i. N

H

(19)

R, S R, / (i)cs,/(ii) acid or alkali I J os | - 5 HSC

Q N N

H

R, acetic

NH,0H-HC1 J anhydride — HON=CH | 5

N .

H

: i — 27 _—

R, :

NC 4 I

N

H

(20)

S R, 0 R,

I 4 H,0, I J

HSC | + HOC

N N

H H

(i) SOCl,/(ii) NH,OH 1 / R, em HNC

N

H

R

POC1, or SOC, 2 / _ > NC I

N

H

’ (21) o 0

Ra I I R

J I ©) cr © ey : —

N NaOH Oc u HN

I

0

Pd ~~ trifluoro- R y acetic Ne 2 R, anhydride y NH; J ——— > CF3 —> NC

CH30H N —

H H

(22) oo

R, R,

J | CF,I J NH, —— a | —

N hv

H N

H

R,

N

H

In the foregoing formulae, Rr R33, Rys Rg, and Y have the same meanings as described above; X is a CF, group or a CCl, group; Ra is an alkyl group; and Q is a protective group.

As the protective groups for Q, an -SO,Rb group, wherein Rb is a dialkylamino group, an alkyl group, or an . optionally alkylated phenyl group; a -CH(Rc)-Rd group, wherein Rc is a hydrogen atom or a methyl group, and Rd is an alkoxy group, a phenyl group which is optionally substituted with an alkyl group or an alkoxy group, or a -OC,H,Si(CH;),, etc. are exemplified.

In each of the processes as described above, the reaction conditions such as reaction temperature, reaction time, solvent, acid acceptor, alkali acceptor, etc. can appropriately be chosen from the conventionally known reaction conditions.

Further, the compounds of the formula

R,

CH, / in the reaction schemes of the processes

N

H

(10), (11), and (12) described above can be prepared by, for example, the following methods: (23) = -

R, _

R, Ay CH, A, or —_— 5

Aj L oo 0) (24)

R

2 -

T CH;-A, —————— - 0 NH, (25)

R

R NH 2 2 2 CH4y-A, / oxidation — > CH 1

HH N

2 Hg H }

Ry

CH, J TiCly ,

N

OH ’

Still further, the compounds of the formula

R, ag in the reaction schemes of the processes

N

H - (13), (21), and (22) described above can be prepared by, for example, the following methods: (27)

R . 2

A,-H

R A 2

T or 2 1 —_—

Ay

No (28)

R, R,

Ry A, HCONH,, HCONH, : or / 4 | _

A, x0 0 —_ 31 —_

rd (29)

R R

2 AO 2

Ry _/A KSCN 7 HNO, or 1 _» HS | —_

Xo H (30)

R, CL R, or Ry "A, guanidine 7 —_— H,

A, _ N— - x0 H (i) diazotization/(ii) reduction

Ee (31)

R

2 1 A,-H —_—

X0 NH, (32)

R H R

2 2 2 A,-H J oxidation

H xm, N

H H

R, {T TiCl, _— >

N

OH

In the foregoing formulae, R, has the same meanings as described above; A, is a halogen atom, an amino group, a hydroxyl group, or an alkanoyloxy group;

A, is a —-CONH, group, a -C(NH)NH, group, or a -C(NH)-A, group, wherein A; is an alkoxy group or an alkylthio group; and A, is a formyl group.

The carbonyl group included in the above described : formulae may be in the latent form of, for example, acetal, thiocacetal, cyclic acetal, cyclic thioacetal, etc.

Further, the formyl group represented by A, may be in the latent form of, for example, acetal, hemiacetal, etc. : In each of the processes as described above, the reaction conditions such as reaction temperature, reaction time, solvent, acid acceptor, alkali acceptor, etc. can appropriately be chosen from the conventionally known ) reaction conditions.

Typical examples of the intermediate compounds represented by the general formula (II), for the imidazole compounds of the present invention represented by the general formula (I) are shown in Table 1.

Table 1

R, wd (II)

Intermediate Melting

No. Ry R2 Rj Point (°C) 1 CN Br H 196-201 2 " 3-trifluoromethyl- " 160-168 phenyl : 3 " Cl CH; 194-196 4 " 4-methoxyphenyl cl 150-155 5 " phenyl CHy 222-225 6 " " Br 120-125 7 " 4-fluorophenyl H 211-213 8 " 4-methylphenyl " 228-232 s 9 " " Br 142-144 " 4-fluorophenyl " 176-178 11 " 3,4-dichlorophenyl H 115-121 12 " 4-methylphenyl Cl 124-129 . 13 " Cl H 150-153 14 " n-C;H, Cl 107-109 " phenyl " 149-151 :

Table 1 (cont'd) :

Intermediate Melting

No. Ry Ro _R3 Point (°C) 16 CN 3-methylphenyl Cl 140-142 17 " 3,4-dimethylphenyl " 150-152 18 " 4-fluorophenyl " 153-155 19 " 4-bromophenyl " 162-167 " 4-ethylphenyl " 141-145 21 " " H 214-217 22 To 3-methoxyphenyl " 218-220 . 23 " 4-nitrophenyl " 230-235 24 " 5-chloro-2-thienyl " 202-206 " SCH, Co 26 " phenylthio " 166-169 27 " phenyl CN 207-215 28 " H F : / 29 " 2-naphthyl Cl 146-149 " " H 253-255 31 " 4-nitrophenyl Cl 189-191 . 32 " 4-chlorophenyl H 215-224 . 33 " 4-chlorophenyl cl 178-181 34 " 2-chlorophenyl " 145-152 " " Br 152-156 \ 36 " 4-jisopropylphenyl H 180-184 37 " 4-methylthiophenyl " 217-219

Ee

Table 1 (cont'd)

Intermediate Melting

No. Ry Rj Rs Point (°C) 38 CN 4-(2',2',2'-trifluoro- H 195-198 ethoxy)phenyl 39 " CH, NO, 125-130 40 " tert-C,Hg Br 120-127 : 41 " 2-methylphenyl H 42 | " " Cl 43 - " 5-methyl-2-furyl H 169-171 44 " 3, 4-dimethoxyphenyl "oo 188-190 45 " 4-ethoxyphenyl " 218-219 } 46 " 3-methyl-4-methoxy- . " 199-205 phenyl 47 " 2-thienyl " 195-203 48 " 4-(2',2',2'-trifluro- Cl 164-166 ethoxy)phenyl 49 " " Br 150-155 50 " 3-methyl-4-methoxy- Cl 145-149 phenyl : 51 " 3-chloro-4-methyl- Br 190-194 phenyl 52 " CH, CN 142-145 53 " C,Hg H 127-129 54 " " Cl 138-140 55 " n-C3H, H 52-54 56 " " I 106-109 57 " n-C,Hg H 83-85 - 36 - Co ad a

Table 1 (cont'd)

Intermediate Melting

No. _R1 R, Rj Point _ (°C) 58 CN n-C,H, Cl 107-109 59 " n-CgH, , H 89-92 60 " n-CgH, , Cl 109-110 61 " iso-C3H, H 88-91 62 : " " Cl 84-87 63 " iso-C,Hy H 64° om " Cl 142-145 65 " tert-C,Hy H 130-135 66 " " Cl 120-124 67 " iso-Cg4H,, : H 144-146 : 68 " " Cl 104-107 69 " cyclopropyl " 170-183 70 " cyclohexyl H 185-190 71 " " Cl 130-133 72 " 3-chloropropyl | " 117-120 73 " CH,OCH, " 74 " CH,0C,H, " 75 " benzyl " 144-146 76 " phenethyl " 147-152 77 " SC,H, H 112-115 78 " " Cl 128-131 79 " S-n-C,H, H 97-99 - 80 " " cl 95-99 pa

Table 1 (cont'd)

Intermediate Melting

No. | Ry Ry Rj Point (°C) 81 : CN 3-fluoropropy:l Cl 82 " SO2N(CHjy), H 175-180 83 " 3-chlorophenyl n 140-143 84 " " Cl 124-128 85 " 2,3-dichlorophenyl H 202-206 86 " " cl 198-204 87° 3-chloro-4-methoxy- " 158-160 phenyl 88 " " | Br 161-163 89 " 3-chloro-4-methyl- Cl 165-169 phenyl 90 " 4-cyanophenyl H 240-244 91 " " Cl 250-255 92 " " i Br 239-244 93 " 4-ethoxyphenyl Cl 151-153 94 neo Br 140-145 . 95 " 2-fluorophenyl H 190-195 96 " " Cl 155-159 97 . " 2-methoxyphenyl H 155-159 98 " " Cl 223-230 99 " 3,4-methylenedioxy- H 228-231 : phenyl 100 " J" Cl 149-152 101 " " Br 166-169 al that R, and Ry are different from each other, the intermediate compounds represented by the general formula (II) described above include tautomers represented by the general formulae (II-a) and (II-b) described below:

H

J Ry N Ry ——

N R N R

H 3 3 - © (II-a) (II-b) wherein R;, R,, and R3 have the same meanings as described hereinabove. Accordingly, in the case that the imidazole compounds of the present invention represented by the general formula (I) are prepared using the compounds represented by the general formula (II) as a starting : material, the imidazole compounds represented by the general forrulae (I-a) and/or (I-b) described below can be "obtained.

S02,

R, N R, ; R, CT and/or w~C

Ry N R,q (I-a) (I-b) i ¢ _ 39 —

pal and R, have the same meanings as described hereinabove. In the case that R, and R; are different from each other, the imidazole compounds represented by the general formulae (I-a) and (I-b) are tautomers each other. The same also applies to the compounds represented by the general formulae (1-1), (I- 5), (1-6), and (I-7) in the processes [B] to [D] described hereinabove, etc.

The imidazole compounds represented by the general formula (I-a) or (I-b) described hereinabove can be separated concretely, for example, by methods [E-1] to [E- 3) described below: [E-1] Method by means of chromatography:

Each compound can be separated from a mixture of jsomers of the general formulae (I-a) and (I-b) described above, by means of silica gel column chromatography, preparative high performance liquid chromatography, flash chromatography, etc. In the case cof silica gel column chromatography, for example, n-hexane, carbon tetrachloride, methylene chloride, chloroform, ethyl acetate, or a mixture thereof can be used as a developing solvent. [E-2] Method by means of recrystallization: :

Each compound can be separated from a mixture of - isomers of the general formulae (I-a) and (I-b) described above, using as a solvent for recrystallization, for

PL 4 : ....e, carbon tetrachloride, methylene chloride, chloro- toi, l,2-dichloroethane, ethyl acetate, diethyl ether, tetrahydrofuran, acetone, or a mixture thereof. [E-3] Method by means of decomposition:

Either compound can be separated from a mixture of isomers of the general formulae (I-a) and (I-b) described above, by the selective hydrolysis under conditions of from 0 to 80°C (preferably from room temperature to 50°C) for from 1 to 48 hours (preferably from 5 to 24 hours). . As _the mixture of isomers used in the methods [E- 1] to [E-3] described above, it ig preferred to use the mixture having a mixing ratio of both isomers as large as possible by appropriately choosing reaction conditions : previously in the process [A] described above, for example, kind of solvent and acid acceptor and amounts thereof to be used, reaction temperature, reaction time, etc.

Further, in the case of preparing imidazole compounds wherein R, is a —CSNH,, group or a -CSNHR; group, wherein Rs; has the same meaning as described hereinabove from compounds wherein R, is a cyano group in the compounds represented by the general formula (I-b)" separated by the method [E-1], [E-2}, or [E-3] described above, such compounds can be obtained, for example, by the ~ following method:

TA BAD OMIGINALL pa

SO,Ry SO,R, r — Ra H,S ; N Ry wl \ at J

N R; dioxane N R triethylamine 3

SO,R,

R.COC1 Oo S N R, ¢ I LC

R.CHNC acetone 6 \ - ~ pyridine N Ry wherein R,, Ry, Ry, and Rg, have the same meanings as described hereinabove.’

Specific examples of synthesizing the imidazole compounds of the present invention are described below.

Synthesis Example 1

Synthesis of 2-cyano-1-dimethylsulfamoylimidazole . (Compound No. 1)

Thirty grams of 2-cyanoimidazole, 53.4 ¢ of an- hydrous potassium carbonate and 600 ml of acetonitrile ’ were mixed at room temperature. After reacting for 2 hours at the refluxing temperature, the reaction mixture was cooled, and 55.6 g of dimethylsulfamoyl chloride was added thereto. The mixture was reacted again at the refluxing temperature for 2 hours.

—

After completion of the reaction, the reaction mixture was poured into water. Extraction with methylene chloride was carried out. After washing with water, the extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation. The obtained residue was purified by silica gel column chromatography (develop- ing solvent: methylene chloride) to give 28.0 g of 2- cyano-l-dimethylsulfamoylimidaznle (Compound No. 1) having a melting point of from 74 to 76°C.

Synthesis Example 2

Synthesis of 2-cyano-l-dimethylsulfamoyl-5- phenylthioimidazole (Compound No. 10-b)

In a four-necked flask were charged 12.0 g of 2- cyano-l-dimethylsulfamoylimidazole (Compound No. 1) and 240 ml of dry tetrahydrofuran in a nitrogen flow. While maintaining the mixture at ~75°C or below with dry ice- acetone, 41.3 ml of a 1.6 M n-butyl lithium hexane solution (manufactured by Aldrich) was gradually added dropwise to the mixture. After completion of the dropwise addition, the system was kept at the same temperature for

B 15 minutes. Then, a solution of 17 g of diphenyl disulfide in 30 ml of tetrahydrofuran was added dropwise to the mixture at -70°C or below. While stirring overnight, the temperature was gradually reverted to room temperature.

After completion of the reaction, the reaction mixture was poured into water. Extraction with 500 ml of ethyl acetate was carried out. After washing with water,

the extract was dried over anhydrous sodium sulfate. The ethyl acetate was removed by distillation, and the residue was purified by silica gel column chromatography (develop- ing solvent: methylene chloride) to give 4.3 g of 2- cyano-1-dimethylsulfamoyl-5-phenylthioimidazole (Compound

No. 19-b) having a melting point of from 106 to 107°C.

Synthesis Example 3

Synthesis of 4-chloro-2-cyano-l-dimethyl- sul famoyl-5-n-propylimidazole (Compound No. 16-b) (L] 4.8 g of 2-cyano-1l-dimethylsulfamoyl-5-n- propylimidazole having a melting point of from 51 to 52°C (Compound No. 3-b) was synthesized by the reaction of 12.0 ‘ g of 2-cyano-1-dimethylsulfamoylimidazole (Compound No. 1) and 15.3 g of n-propyl jodide in a manner similar to

Synthesis Example 2 described above. p (2) 4.8 g of 2-cyano-1-dimethylsulfamoyl-5-n- propylimidazo}e as obtained in [1] above, 40 ml of pyridine, and 11.4 g of pyridinium chloride were mixed, and the mixture was stirred at 90°C for 4 hours. After completion of the reaction, the pyridine was removed by distillation from the reaction mixture, and the residue was extracted with ethyl acetate. The extract was washed with water and then dried over anhydrous sodium sulfate.

Thereafter, the ethyl acetate was removed by distillation, and the residue was purified by silica gel column chromatography (developing solvent: a mixture of ethyl acetate and n-hexane) and separated to give 2.46 g of 2-

r (hb) -n-propylimidazole (Intermediate No. 55) having

Ra melting point of from 52 to 54°C. ‘ [3] 2.35 g of 2-cyano-4(5)-n-propylimidazole as 1 obtained in [2] above, 80 ml of chloroform, and 2.6 g of oN N-chlorosuccinimide were mixed, and the mixture was reacted at the refluxing temperature for 4 hours. After completion of the reaction, 200 ml of water was added to the reaction mixture. The resulting organic layer was washed with water and then dried over anhydrous sodium sulfate. After drying, the chloroform was removed by : distillation, and the residue was purified by silica gel column chromatography (developing solvent: a 1:1 mixture of ethyl acetate and n-hexane) and separated to give 2.2 g of 4(5)-chloro-2-cyano-5(4)-n-propylimidazole (Inter- mediate No. 14) having a melting point of from 107 to 109°C {4) 2.0 g of 4(5)-chloro-2-cyano-5(4)-n-propyl- . imidazole as obtained in [3] above, 30 ml of acetonitrile, 1.95 g of anhydrous potassium carbonate, and 1.86 g of dimethylsul famoyl chloride were mixed, and after gradually : elevating the temperature, the mixture was reacted at the refluxing temperature for 1 hours. After completion of the reaction, the acetonitrile was removed by distillation from the reaction mixture. After pouring 100 ml of water into the residue, the resulting mixture was extracted with 50 ml of methylene chloride. ‘he extract was washed with

BAD ORIGINAL

, pe . water and .dried over anhydrous sodium sulfate. There- after, the methylene chloride was removed by distillation.

The residue was allowed to stand overnight, and the analysis thereof revealed that one of the two isomers in the mixture decomposed and returned to the starting 4(5)- chloro-2-cyano-5(4)-n-propylimidazole. The residue containing the other isomer was purified by silica gel column chromatography (developing solvent: methylene chloride) and separated to give 1.1 g of 4-chloro-2-cyano- 1-dimethylsylfamoyl-5-n-propylimidazole (Compound No. 16- b) having a melting point of from 64 to 66°C.

Synthesis Example 4 : Synthesis of 2-cyano-l-dimethylsulfamoyl-4(5)- phenylimidazole (Compound No. 4) } {1] In 320 ml of acetone was dissolved 23.04 g of 4(5)-phenylimidazole, and 12.14 g of anhydrous potassium carbonate was added to the solution. The mixture was heated at the refluxing temperature for 2 hours. After cooling, 45 ml of an acetone ‘solution containing 25.25 g of dimethylsulfamoyl chloride was added dropwise to the mixture. After completion of the dropwise addition, the mixture was heated at the refluxing temperature for 4.5 hours to complete the reaction.

After completion of the reaction, the reaction mixture was cooled, and solid substances were removed by ‘ filtration. After the solvent was removed by distillation under reduced pressure, the residue was purified by silica gel column chromatography (developing solvent: methylene ! chloride) to give 17.8 g of 1-dimethylsulfamoyl-d(5)- phenylimidazole having a melting point of from 96 to 100°C. {2] In 290 ml of tetrahydrofuran was dissolved 17 g of 1-dimethylsulfamoyl-4(5)~phenylimidazole as obtained in [1] above. The solution was cooled to -70°C in a nitrogen flow, and 51 ml of a 1.6 M n-butyl lithium hexane solution was added dropwise to the mixture over 30 minutes. After completion of the dropwise addition, the reaction mixture was stirred at -70°C for 30 minutes. ’

Then, 12 ml of a tetrahydrofuran solution containing 6 g of N,N-dimethylformamide was added dropwise to the mixture. After completion of the dropwise addition, the reaction mixture was reacted for 15 hours with stirring while slowly elevating the temperature to room temperature. : After completion of the reaction, the reaction mixture was poured into ice water and extracted with ethyl acetate. After washing the extracted layer with water, ‘ the extracted layer was dried over anhydrous sodium 3 sulfate. The solvent was distilled off under reduced 3 pressure, and the residue was purified by silica gel : column chromatography (developing solvent: a 1:2 mixture 4 ~ of ethyl acetate and n-hexane) to give 12.8 g of 1- 4 | - 47 -

: ; 5 oo dimethylsulfamoyl-2-formyl-4(5)-phenylimidazole having a melting point of from 86 to 89°C.

[3] In 120 ml of pyridine were dissolved 11.16 g of 1l-dimethylsulfamoyl-2-formyl-4(5)-phenylimidazole as obtained in [2] above and 5.56 g of hydroxylamine hydrochloride, and 24 ml of acetic anhydride was added dropwise to the solution at room temperature. After : completion of the dropwise addition, the temperature was gradually raised, and the mixture was reacted at 100°C for 12 hours. .

After completion of the reaction, the solvent in the reaction mixture was removed by distillation under reduced pressure. Then, 125 ml of water was added to the residue, and the precipitated solid was separated by filtration. The crude product was dissolved in. ethyl acetate and purified by silica gel column chromatography (developing solvent: ethyl acetate) to give 5.55 g of 2- cyano-4(5)-phenylimidazole having a melting point of from 203 to 205°C. ’ [4] In 88 ml of acetone was dissolved 1.7 g of 2- cyano-4(5)-phenylimidazole as obtained in [3] above, and . 1.7 g of anhydrous potassium carbonate was added to the solution. The mixture was heated ‘at the refluxing — temperature for 2 hours. ’ After cooling, 6 ml of an acetone solution containing 1.7 g of dimethylsulfamoyl chloride was added 7

7 dropwise to the mixture. After completion of the dropwise r addition, the mixture was heated at the refluxing temperature for 2 hours to complete the reaction.

After completion of the reaction, the reaction mixture was cooled, and solid substances were removed by filtration. After the solvent was removed by distillation under reduced pressure, the residue was extracted with ‘ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate. The solvent was removed by -distillation under reduced pressure to give 2 g of 2-cyano-l-dimethylsulfamoyl-4(5)-phenylimidazole (Compound No. 4) having a melting point of from 101 to 102°C.

Synthesis Example 5

Synthesis of 4(5)-chloro-2-cyano-1-dimethylsulfamoyl-5(4)- phenylimidazole (Compound No. 17) and 4-chloro-2-cyano-1- dimethylsulfamoyl-5-phenylimidazole (Compound No. 17-b)

[1] In 100 ml of chloroform was dissolved 1.352 g of 2-cyano-4(5)-phenylimidazole, and 1.175 g of N-chloro- succinimide was added to the solution. The mixture was reacted upon heating at the refluxing temperature for 4 hours.

After completion of the reaction, the reaction mixture was poured into water and extracted with chloro- form. After washing with water, the extracted layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was ve pd by silica gel column chromatography (developing solvent: methylene -chloride) to give 1.28 g of 4(5)- chloro-2-cyano-5(4)-phenylimidazole (Intermediate No. 15) having a melting point of from 149 to 151°C. , [2] In 6 ml of acetone was dissolved 0.43 g of 4(5)-chloro-2-cyano-5(4)-phenylimidazole as obtained in

[1] above, and 0.29 g of anhydrous potassium carbonate and 0.36 g of dimethylsulfamoyl chloride were added to the solution. ° The mixture was reacted upon heating at the refluxing temperature for 30 minutes.

After completion of the reaction, the ceaction mixture was poured into water and extracted with ethyl acetate. After washing with water, the extracted layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was then purified by silica gel column chromatography (developing solvent: methylene chloride) to give 0.5 g of 4(5)-chloro-2-cyano-l-dimethylsulfamoyl-5(4)- phenylimidazole (Compound No. 17) having a melting point : of from 106 to 109°C. i As a result of analysis by means of NMR spectra, the compound described above was an isomer mixture of 4- chloro-2-cyano-1-dimethylsulfamoyl-5-phenylimidazole and 5-chloro-2-cyano-l-dimethylsulfamoyl-4-phenylimidazole in ~ almost equal ratios. —_ 50 —

Rua edn

_ allowing to stand for 24 hours at room temperature, 2.9 g of the mixture of these isomers as obtained in a manner similar to [2] above was purified by silica gel column chromatography (developing solvent: methylene chloride) to give 1.15 g of 4-chloro-2-cyano-l-= dimethylsulfamoyl-5-phenylimidazole (Compound No. 17-b) having a melting point of from 109 to 112°C. Further, by purification of and isolation from this compound, 0.7 9 of 4(5)-chloro-2-cyano-5(4)-phenylir dazole (Intermediate No. 15) was also obtained.

Synthesis Example 6 synthesis of 4(5)-chloro-2-cyano-1-dimethylsulfamoyl- 5(4)-(4-methylphenyl)imidazole (Compound No. 18) and 4-

Sm eyano-1-dimethylsulfamoyl-5-(4-methylphenyl)= imidazole (Compound No. 18-b)

An isomer mixture (Compound No. 18), having a melting point of from 101 to 108°C, of 4-chloro-2-cyano-1- dimethylsulEamoyl-5-(4-methylphenyl)imidazole and 5-

Cb loro-2-cyano-1-dimethylsul famoyl-4-(4-methylphenyl) imid- . azole was obtained from 4(5)-(4-methylphenyl)imidazole in a ratio of 6:4 in a manner similar to Synthesis Examples 4 and 5 described above. pfter 0.75 g of the isomer mixture was reacted at 40°C for 8 hours, the reaction mixture was purified by silica gel column chromatography (developing solvent: methylene chloride) to give 0.45 g of 4-chloro-2- ” oyano-1-dimethylsulfamoyl-5=(47methylphenyl)inidazole (Compound No. 18-b) having a melting point of from 133 to 134°C. Further, by purification of and isolation from en .

this compound, 0.15 g of 4(5)-chloro-2-cyano-5(4)-(4- methylphenyl)imidazole (Intermediate No. 12) having a melting point of from 124 to 129°C was also obtained.

Synthesis Example 7

Synthesis of 4(5)-chloro-5(4)-(4-chlorophenyl)-2- cyano-1-dimethylsulfamoylimidazole (Compound No. 23), 4-chloro-5-(4-chlorophenyl)-2-cyano-l-dimethyl- sulfamoylimidazole (Compound No. 23-b) and 5-chloro- 4-(4-chlorophenyl)-2-cyano-l-dimethylsulfamoylimid- azole (Compound No. 23-a)

In a manner similar to Synthesis Examples 4 and 5 described above, 0.80 g of an isomer mixture (Compound No. 23), having a melting point of 108°C, of 4-chloro-5-(4- chlorophenyl)-2-cyano-l-dimethylsulfamoylimidazole and 5- chloro-4-(4-chlorophenyl)-2-cyano-1l-dimethylsulfamoylimid- azole was obtained from 4(5)-(4-chlorophenyl)imidazole. ) The isomer mixture was purified by silica gel column chromatography (developing solvent: methylene chloride).

The eluate of the second fraction was concentrated and recrystallized from methylene chloride to give 0.16 g of 4-chloro-5-(4-chlorophenyl)-2-cyano-1l-dimethyl- sulfamoylimidazole (Compound No. 23-b) having a melting . point of from 117 to 120°C. Further, the eluate of the first fraction was likewise concentrated and recrystalliz- ed from methylene chloride to give 0.50 g of 5-chloro-4- (4-chlorophenyl)-2-cyano-l-dimethylsulfamoylimidazole (Compound No. 23-a) having a melting point of from 133 to . 138°C.

Synthesis of l1-dimethylsulfamoyl-4(5)-phenyl- imidazole-2-carbothioamide (Compound No. 49) :

In 30 ml of dioxane was dissolved 1.0 g of 2- cyano-l-dimethylsulfamoyl-4(5)-phenylimidazole (Compound

No. 4), and 0.36 g of triethylamine was added to the : solution. The mixture was heated to 40 to 50°C while stirring, and a hydrogen sulfide gas was introduced thereinto for one hour and 25 minutes. Thereafter, the mixture was reacted at 40 to 50°C for an additional 50 minutes. ’

After completion of the reaction, the reaction mixture was cooled, poured into water, and extracted with

Co ethyl acetate. After washing with water, the extracted layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent: a 1:3 mixture of ethyl acetate and n- ~ hexane) to give 0.8 g of 1-dimethylsulfamoyl-4(5)-phenyl- imidazole-2-carbothioamide (Compound No. 49) having a : melting point of from 155 to 175°C. Crystals of 4(5)- phenylimidazole-2-carbothioamide were also obtained in a small quantity.

Synthesis Example 9 : Synthesis of 2-cyano-l-isopropylsulfonyl-4(5)- phenylimidazole (Compound No. 101)

- One gram of 2-cyano-4(5)-phenylimidazole, 0.98 g of anhydrous potassium carbonate, and 30 ml of aceto- nitrile were mixed at room temperature. After reacting for 2 hours at the refluxing temperature, the reaction * mixture was cooled, and a solution of 1.0 g of isopropylsulfonyl chloride in 5 ml of acetonitrile was added thereto. The mixture was reacted again at the refluxing temperature for 1.5 hours.

Bfter completion of the reaction, the reaction mixture was poured into water. Extraction with methylene chloride was carried out. After washing with water, the extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue ‘was purified by silica gel column chromatography (developing solvent: methylene chloride) to give 1.4 g of 2-cyano-l-isopropylsulfonyl- 4(5)-phenylimidazole (Compound No. 101) having a melting point of from 80 to 83°C.

Synthesis Example 10

Synthesis of 4(5)-(2-thienyl)-2-cyano-1-di- methylsulfamoylimidazole (Compound No. 6)

[1] To 150 ml of formamide was added 25 g of 2- (bromoacetyl)thiophene. The mixture was reacted at 180 to 190°C for 2 hours.

After completion of the reaction, the reaction mixture was poured into water, and concentrated hydrochloric acid was added thereto to render the system acidic. Then, washing with methylene chloride was carried out. After neutralizing with ammonia water, the aqueous phase was extracted with methylene chloride. After washing with water, the extract was dried over anhydrous sodium sulfate, The solvent was removed by distillation under reduced pressure to give 11 g of 4(5)-(2-thienyl)- imidazole.

[2] To 200 ml of acetonitrile were added 11.6 g of dimethylsulfamoyl chloride, 11.1 g of anhydrous potassium carbonate, and 11 g of 4(5)-(2-thienyl)imidazole as obtained in [1] above. The mixture was reacted for 2 hours while stirring.

After completion of the reaction, the reaction mixture was poured into water. Extraction with ethyl acetate was carried. out. After washing with water, the extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure to give 14.5 g of 4(5)-(2-thienyl)-1-dimethylsulfamoyl- imidazole. :

A [31] In 120 ml of anhydrous tetrahydrofuran was ' dissolved 9.5 g of 4(5)-(2-thienyl)-1-dimethylsulfamoyl- imidazole as obtained in [2] above. In a nitrogen flow, 26.2 ml of a 1.6 M n-butyl lithium hexane solution was added dropwise to the solution at -78°C, and the mixture “was stirred at the same temperature for 15 minutes. Then, ml of a tetrahydrofuran solution having dissolved therein 5.4 g of N,N-dimethylformamide was added dropwise to the mixture. After completion of the dropwise addition, the temperature was gradually reverted to room temperature to complete the reaction.

After completion of the reaction, the reaction mixture was poured into water. Extraction with ethyl acetate was carried out. After washing with water, the . extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure to give 5.4 g of 4(5)-(2-thienyl)-2-formyl-1-dimethyl- sulfamoylimidazole.

[4] In 54 ml of pyridine were dissolved 2.6 g of hydroxylamine hydrochloride and 5.4 g of 4(5)-(2-thienyl)- 2-formyl-1-dimethylsulfamoylimiazole as obtained in [3]) above. The solution was stirred at room temperature for minutes. Then, 10 ml of acetic anhydride was gradually added to the solution, followed by reacting at 60 to 70°C for 2 hours.

After completion of the reaction, the reaction mixture was poured into water. Extraction with ethyl acetate was carried out. After washing with water, the : extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel "column chromatography (developing solvent: a 2:1 mixture of ethyl acetate and n-hexane) to give 1.2 g of 4(5)-(2- . - 56 -

EEE pan (Intermediate No. 47) having a melting point of from 195 to 203°C.

[5] To 50 ml of acetonitrile were added 1.1 g of dimethylsulfamoyl chloride, 1.0 g of anhydrous potassium carbonate, and 1.2 g of 4(5)-(2-thienyl)-2-cyanoimidazole as obtained in [4) above. The mixture was reacted at the refluxing temperature for 2 hours. ~ After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. After drying the extract over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent: methylene chloride) to give 1.3 g of 4(5)-(2-thienyl)-2-cyano-1- dimethylsulfamoylimidazole (Compound No. 6) having a melting point of from 145 to 150°C

Synthesis Example 11

Synthesis of 4(5)-chloro-2-cyano-l-dimethyl- sulfamoyl—-5(4)-isopropylimidazole (Compound No. 125) and 4-chloro-2-cyano-l-dimethylsulfamoyl-5- ] . isopropylimidazole (Compound No. 125-b)

[1] 360 g of formamide was heated to 180°C, and 102 g of 1-hydroxy-3-methyl-2-butanone (prepared in a manner as described in Lipshutz and Morey, J. Org. Chem., - 48, 3745 (1983)) was added dropwise thereto over 30 minutes. After completion of the dropwise addition, the mixture was reacted at 180°C for one hour.

After completion of the reaction, the reaction

Bh mixture was cooled and poured into ice water. The resulting mixture was adjusted at a pH of 1 with hydrochloric acid and washed with methylene chloride. The aquesus layer was adjusted at a PH of 4 to 5 with ammonia water. 5 g of activated charcoal was added thereto, and the mixture was stirred for one hour. The attivated charcoal was removed by filtration, and the filtrate was adjusted at a PH of 8 with ammonia water.

Then, extraction with methylene chloride was carried out, and the extract was dried over anhydrous sodium sulfate.

The solvent was distilled off under reduced pressure to give 13 g of 4(5)-isopropylimidazole.

[2] In 300 ml of acetonitrile was dissolved 11.8 g of 4(5)-isopropylimidazole as obtained in [1) above, and 18 g of anhydrous potassium carbonate was added to the solution. The mixture was refluxed for 30 minutes, and after cooling, 17 gq of dimethylsulfamoyl chloride was : added dropwise thereto. After completion of the dropwise addition, the mixture was refluxed to complete the . reaction.

After completion of the reaction, the reaction mixture was cooled, poured into water, and then extracted with ethyl acetate. The extracted layer was washed with "water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the

ARR residue was purified by silica gel column chromatography (developing solvent: methylene chloride) to give 13 gq of 1-dimethylsulfamoyl~4(5)-isopropylimidazole.

[3] In 200 ml of tetrahydrofuran was dissolved 13 g cf 1-dimethylsulfamoyl-4(5)-isopropylimidazole as ° obtained in [2] above. The solution was cooled to -70°C in a nitrogen flow, and 38 ml of a 1.6 M n-butyl lithium hexane solution was added dropwise thereto over 15 minutes. After completion of the dropwise addition, the mixture was stirred at -7g°C for' 30 minutes. After dropwise addition of 5.6 g of N,N-dimethylformamide, the mixture was reacted with stirring for 15 hours while slowly elevating the temperature to room temperature.

After completion of the reaction, the reaction mixture was poured into ice water and extracted with ethyl acetate. The extracted layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 8.6 g of 1- dimethylsulfamoyl-2-formyl-4(5)-isopropylimidazole.

[4] In 100 ml of pyridine were dissolved 8.5 g of 1-dimethylsulfamoyl-2-formyl-4(5)-isopropylimidazole as obtained in [3] above and 4.8 g of hydroxylamine hydrochloride, and 10 ml of acetic anhydride was added dropwise to the solution at room temperature. After completion of the dropwise addition, the temperature was

BAD ORIGINAL v sn gradually elevated, and the mixture was reacted at 80 to 90°C for 5 hours.

After completion of the reaction, the solvent in the reaction mixture was distilled off under reduced pressure. To the residue was added water, and the mixture was extracted with ethyl acetate. The extracted layer was washed with dilute hydrochloric acid and then with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 2.35 g of 2- cyano-4(5)-isopropylimidazole (Intermediate No. 61) having a melting point of from 88 to 91°C.

[5] In 80 ml of methanol was dissolved 2 g of 2- cyano—-4(5)-isopropylimidazole as obtained in [4] above, and 2.1 g of N-chlorosuccinimide was added to the solution. The mixture was stirred at room temperature for hours and then reacted at 40°C for 8 hours. . After completion of the reaction, the methanol in the reaction mixture was distilled off under reduced pressure. To the residue was added water, and the mixture . was extracted with ethyl acetate. The extracted layer was washed with water and dried over anhydrous sodium sulfate.

The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent: methylene chloride) to . "give 1.67 g of 4(5)-chloro-2-cyano-5(4)-isopropylimidazole

I oc ® . oo | ’ (Intermediate No. 62) having a melting point of from 84 to 87°C. / [6] In 30 ml of acetonitrile was dissolved 1.6 g of 4(5)-chloro-2-cyano-5(4)-isopropylimidazole as obtained "in [5] above, and 1.56 g of anhydrous potassium carbonate ) was added to the solution. The mixture was refluxed for minutes. After cooling, 1.49 g of dimethylsulfamoyl chloride was added dropwise thereto. After completion of the dropwise addition, the mixture was refluxed for 15 minutes to complete the reaction.

After completion of the reaction, the reaction mixture was cooled, poured into water, and then extracted with ethyl acetate. The extracted layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent: methylene chloride) to give 2.1 g of 4(5)-chloro-2-cyano-l-dimethylsulfamoyl-5(4)-isopropyl- : imidazole (Compound No. 125).

As a result of analysis by means of NMR spectra, the compound described above ‘was an isomer mixture of 4- chloro-2-cyano-l-dimethylsulfamoyl-5-isopropylimidazole and 5-chloro-2-cyano-1-dimethylsulfamoyl-4-isopropylimid- azole in a proportion of about 2:1.

[7] After allowing to stand for 5 days at room temperature, 2.1 g of the isomer mixture as obtained in . Ku

[6] above was purified by silica gel column chromatography (developing solvent: methylene chloride) to give 1 g of 4- chloro-2-cyano-l-dimethylsulfamoyl-5-isopropylimidazole (Compound No. 125-b) having a melting point of from 75 to 82°C (decomposed). Further, by purification of and isolation from this compound, 4(5)-chloro-2-cyano-5(4)- isopropylimidazole (Intermediate No. 62) was also : obtained.

Synthesis Example 12

Synthesis of 4-chloro-l-dimethylsulfamoyl-5-n-propyl- imidazole—-2-carbothioamide (Compound No. 185-b)

[1] In a four-necked flask were charged 6.0 g of 2-cyano—4,5-dichloro-l1-dimethylsulfamoylimidazole having a melting point of from 100 to 103°C and 180 ml of dry tetrahydrofuran in a nitrogen flow. While maintaining the mixture at -75°C or below with dry ice-acetone, 15.3 ml of a 1.6 M n-butyl lithium hexane solution (manufactured by

Aldrich) was gradually added dropwise to the mixture.

After completion of the dropwise addition, the system was kept at the same temperature for 15 minutes. Then, a solution of 5.7 g of n-propyl iodide in 15 ml of tetrahydrofuran was added dropwise to the mixture at -70°C or below. While stirring overnight, the temperature was gradually reverted to room temperature. : After completion of the reaction, the reaction mixture was poured into water. Extraction with 500 ml of methylene chloride was carried out. After washing with

" hare 2 water, the extract was dried over anhydrous sodium sulfate. The methylene chloride was removed by distillation, and the residue was purified by silica gel column chiomatography (developing solvent: methylene chloride) and then again purified by silica gel column chromatography (developing solvent: a mixture of ethyl acetate and n-hexane) to give 2.8 g of 4-chloro-2-cyano-1- dimethylsulfamoyl-5-n-propylimidazole (Compound No. 16-b) having a melting point of from 66 to 68°C. . [2} In a four-necked flask were charged 2.7 g of 4-chloro-2-cyano-l-dimethylsulfamoyl-5-n-propylimidazole as obtained in [1] above, 40 ml of dioxane, 1.0 g of triethylamine, and 0.8 g of pyridine. Into this mixture was introduced a hydrogen sulfide gas at 20 to 25°C for about 30 minutes until the starting materials had : disappeared.

After completion of the reaction, the reaction } mixture was poured into water, and precipitated crystals were filtered by means of .a Nutsche and dried. The resulting crystals were purified by silica gel column chromatography (developing solvent: methylene chloride) and separated to give 2.3 g of 4-chloro-1-d4i- methylsulfamoyl-5-n-propylimidazole-2-carbothioamide (Compound No. 185-b) having a melting point of from 160 to 162°C. :

pao cn 0 Ee

Synthesis Example 13

Synthesis of N-propionyl-4-chloro-l-dimethylsulfamoyl-5- n-propylimidazole-2-carbothioamide (Compound No. 187-b)

Into a four—necked flask were charged 2.0 g of 4- chloro-l-dimethylsulfamoyl-5-n-propylimidazole-2- carbothioamide (Compound No. 185-b), 24 ml of acetone, and 1.12 g of py! .dine. 1.19 g of propionyl chloride was added dropwise to the mixture at 0 to 5°C. After completion of the dropwise addition, the reaction was carried out at 30 to 35°C for one hour and at the refluxing temperature for an additional 30 minutes .with stirring.

After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The extracted layer was washed with water and dried over anhydrous sodium sulfate. Thereafter, the ethyl acetate was removed by distillation, and the residue was purified by silica gel column chromatography : (developing solvent: methylene chloride) and separated to give 1.02 g:{of N-propionyl-4-chloro-l-dimethylsulfamoyl-5- n-propylimidazole-2-carbothicamide (Compound . No. 187-b) having a melting point of from 150 to 152°C.

Synthesis Example 14

Synthesis of 2-cyano-l-dimethylsulfamoyl-4,5-diphenyl- thioimidazole (Compound No. 141)

[1] 8.0 g of 2-cyano-l-dimethylsulfamoyl-5- phenylthioimidazole (Compound vo. 10-b) as obtained in a similar manner to Synthesis Example 2 described above, 60 ml of methanol, and 60 ml of a 7% hydrochloric acid aqueous solution were charged, and the mixture was reacted with stirring at 40 to 50°C for 2 hours. After completion of the reaction, the reaction mixture was rendered weakly alkaline with ammonia, and precipitated crystals were separated by filtration and dried to give 4.2 g of 2- cyano-4(5)-phenylthioimidazole (Intermediate No. 26) having a melting point of from 166 to 169°C. . [2} To a mixture of 4.2 g of 2-cyano-4(5)- phenylthioimidazole as obtained in [1] above, 80 ml of acetonitrile, and 3.1 g of anhydrous potassium carbonate was added 3.4 g of dimethylsulfamoyl chloride. The resulting mixture was reacted at the refluxing temperature for one hour. After completion of the reaction, the reaction mixture was cooled, and solid substances were : filtered. The solvent in the filtrate was removed by distillation, and the residue was purified by silica gel column chromatography (developing solvent: methylene . chloride) and separated to give 5.8 g of 2-cyano-1- dimethylsulfamoyl-4(5)-phenylthioimidazole (Compound No. 10).

[3] In a four—necked flask were charged 5.8 g of 2-cyano-l-dimethylsulfamoyl-4(5)-phenylthioimidazole as " obtained in [2] above and 150 ml of dry tetrahydrofuran in a nitrogen atmosphere, and 12.9 ml of a 1.6 M n-butyl

, - lithium hexane solution (manufactured by Kanto Kagaku) was added dropwise to the mixture while maintaining the temperature at -75°C or below with dry ice-acetone. After completion of the dropwise addition, the mixture “was kept at the same temperature for 15 minutes, and 20 ml of a solution of 5.2 g of diphenyl disulfide in tetrahydrofuran was added dropwise thereto at -70°C or below. Thereafter, the mixture was returned to room temperature. After completion of the reaction, the reaction mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate. The solvent was removed by distillation, and the residue was purified by silica gel column chromatography (developing solvent: methylene chloride) and separated to give 1.7 g of 2-cyano-l-dimethylsulfamoyl-4,5-diphenylthioimidazole (Compound No. 141) having a melting point of from 98 to 101°C.

Synthesis Example 15

Synthesis of 4~bromo-2-cyano-l-dimethylsulfamoyi~5-n- propylimidazole (Compound No. 157-b)

[1] 2-Cyano-4,5-dibromo-1 - dimethylsulfamoylimidazole having a melting point of from 118 to 120°C was synthesized from 2-cyano-4,5-dibromo- imidazole having a melting point of from 200 to 203°C in a . similar manner to Synthesis Example 1 described above.

[2] In a 200 ml four-necked flask were charged 5 g of 2-cyano-4,5-dibromo-l-dimethylsulfamoylimidazole as obtained in [1] above and 120 ml of dry tetrahydrofuran in a nitrogen flow. While maintaining the mixture at =75°C or below with dry ice-acetone, 9.6 ml of a 1.6 M n-butyl lithium hexane solution (manufactured by Aldrich) was gradually added dropwise to the mixture. After completion of the dropwise addition, the system was kept at the same temperature for 15 minutes. Then, a solution of ‘3.6 g of n-propyl iodide in 15 ml of tetrahydrofuran was added dropwise to the mixture at -75°C or below. While stirring, the temperature was gradually reverted to room temperature.

After completion of the reaction, the reaction mixture was extracted with ethyl acetate. After washing with water, the extract was dried over anhydrous sodium sulfate. The ethyl acetdte was removed by distillation, and the residue was purified by silica gel column chromatography (developing solvent: methylene chloride) to give 2.1 gq of 4-bromo-2-cyano-1-~dimethylsulfamoyl-5-n- propylimidazole (Compound No. 157-b) having a melting point of from 93 to 94°C. - 67 -

Bl

NRReRE

Typical examples of the imidazcle compounds (general formula (I)) of the present invention are shown in Table 2.

Table 2

Ry = R, g 1 (I)

AA,

SO,R,

Compound Melting

No. . Ri ] Ro R3 Rg Point (°C) 1 CN H H -N(CH;), 74-76 2 " CH, " " 78-83 3 " n-C3H, " " 4 " phenyl " " 101-102 " 4-chlorophenyl " " 148-149 6 gl 2-thienyl " " 145-150 7 " 5-chloro-2- " " 145-148 thienyl 8 " 5-bromo-2- " " 138-140 . thienyl 9 " SCH, " " " phenylthio " " 11 " 2-chlorophenyl " " 118-121 12 " 4-nitrophenyl " " 107-108 13 Soom 4-trifluoro- " " methylphenyl 14 " H Cl "

> Table 2 (cont'd)

Compound Melting

No. Ry Ry Rj Ry Point : (°C) 15 CN CH, Cl -N(CHy), 16 " n-C,H, 1" " 17 " phenyl " " 106-109 18 " 4-methylpheny? " " 101-108 19 " 3-methylphenyl " " 90-95 20 " 2-methylphenyl " " i. 21 © on 3,4-dimethyl- " " 95-105 phenyl 22 " 4-methoxyphenyl " " 102-107 3 23 " 4-chlorophenyl " " 108 24 " 2~chlorophenyl " " 25 " 3,4-dichloro- " " 99-105 phenyl 26 " 4-fluorophenyl " " 105-107 27 " SCH, " " ~ 28 " phenylthio " ! : 29 " H Br " ] 30 LL} CH, " 1" : 31 " tert-C, Hq " " 88-90 32 " phenyl " " a 33. 4-methylphenyl "106-108 2 34 " 4-tert-butyl- " "105-110 : phenyl g 35 " 4-methoxyphenyl " " 96-99 { - - 69 - awd

~~ : Table 2 (cont'd)

Compound Melting

No. Rj Ra Rj Rg Point (°C) 36 CN 4-fluorophenyl Br -N(CH;), 87-93 37 " 4-chlorophenyl " " 38 " 1,2-dibromo- Cl " ethyl } 39 " C,Hg Br n 40 " -CH,CH=CH, " " 41 " 4-bromophenyl Cl " 110-116 42 - on 4-isopropyl- " " phenyl 43 " 2-naphthyl " 124-126 . 44 " CH, CH, " 52-54 45 " phenyl " " 101-105 46 ” " SCH, 1" 47 " " phenyl " 148-149 48 " " CN " 124-129 49 phenyl H " 155-175 ~CSNH, ’ 50 " 4-chlorophenyl " " 197-201 51 " phenyl Cl "110-130 52 ! H Br " 140-144 53 ” phenyl h ” 54 CN 3,4-dimethoxy- H " phenyl 55 " 3-methyl-4- Cl no methoxyphenyl — 70 —_

\ rn : . o . R iy g ad = or © oa - » 26189

Table 2 (cont'd)

Compound Melting

No. R; Rj Rj Ry Point (°C) 56 CN 4-ethylphenyl Cl ~N(CHy), 57 " phenylithio Br " 58 " benzyl " " 59 " 3~chloropropyl H " = 60 " —S50,C,H, tH n 61 " 3-fluoropropyl Cl " 62 _ =" 4-methylthio- H " phenyl 63 " vinyl Cl " 64 " S-methyl-2- H " ; thienyl 65 " 2-chlorophenyl Br " 66 " 3,4-dichloro- H " 139-142 phenyl 67 " 4-(2',2',2'- Cl " trifluoroethoxy)- phenyl 6 8 " " Br " 69 " —-CH,OH H " 70 " 3-chlorophenyl Cl " 71 " 3-fluorophenyl " " 72 " 2-fluorophenyl " " 96-101 73 oo" ~SCH,CH=CH,, H " 74 " CH, NO, " 110-117 .

re Table 2 (cont'd) y Compound Melting

No. Ry R2 _R3 _Rq Point (°C)

Re) 75 CN | H -N(CH;), -cu <0) . (1,2-diphenylethyl) 7 76 " -ca <0) " " (a-hydroxybenzyl)

I

77 " -ca~<O)-c1 " " (4~chloro-a- hydroxybenzyl) 78 ” -c<O)-c1 mn 1" . (4—-chlorobenzoyl) 79 " acetyl " " 0 80 ~CNHCCH phenyl " " (N-acetylthio- ; carbamoyl) i 0 81 ~CNHCCH,CH,C1 ~~" " " [N-(3-chloro- propionyl)- thiocarbamoyl]

CT Table 2 (cont'd) 4 Compound Melting

No. R; Ro Rj ] Rg Point (°C) 82 N-acetyl- CHgy H “N(CHy), ’ thiocarba- moyl

S oO 83 I I 1" " 1" wit 0) (N-benzoylthio- carbamoyl) 84 CN 5-methyl-2- " " 120-124 furyl 85 " C,H; C1 l-piperid- inyl 86 ”n n ”" phenyl 87 " 4-(chloro- H -N(CH;3), 142-146 methylthio)- phenyl 88 " CH, CN " 80-84 89 " cyclohexyl H " 90 " —~50,CH, " " 91 " 4-chloro- " " benzenesulfonyl 92 " phenyl C1 C,Hg 93 " " " cyclo- hexyl 94 "n "n 1" CF, 95 " ! " 2-thienyl

Hs 96 ”" ” ” -N ~

C,H,

iy Table 2 (cont'd)

Compound Melting

No. Rl Rp Ry Rg _Point (°C) a 97 CN phenyl Cl “N

CH, CF,

Ms 98 " " " -N ~

CH,CH=CH, 99 " " " l-pyrrol- idinyl 100 " 4-methylphenyl " morpholino 101 " phenyl H isopropyl 80-83 102 " " cl " 103 " " " -N(C,Hg), 70-80 104 n" 1" Br n 55-76 105 " " Cl morpho- 106-110 lino 106 " " Br " 70-83 107 " " Cl thio- morpholino 108 " 4—(2'-chloro- " -N(CH;), ethyl)phenyl 109 " 4-chlorobenzyl Br " 110 " benzyl H " 111 " 4-chloro- Cl " nhenylthio 112 " 3-chloropropyl " " i 112 ” C,Hg " 11 114 " 2-furyl 2-furyl " 118-123 115 " 4-pyridyl H " 138-142

Table 2 (cont'd)

Melting

No. Ry Ra Rj _ Ry Point (°C) 116 CN 2-thienyl Cl -N(CH,), 117 " 4-fluoro-n-butyl " " : 118 " 5-fluoropentyl " " 119 E n-C,H, " " 120 " n-CgH,, Cw " 121 " n-CgH, 4 " " 122 " n-C,H, " " 123 " n-CgH,, " " 124 " n-C,,H,g " " 125 " iso-C4H, " " 126 ! is0-C,H, " " 127 " tert-C Hy " " 128 " cyclopropyl 129 " cyclohexyl " " 136: " ~CH,CH=CH, " " v 131 " geranyl (C;H;;) " " 132 " SC, Hy " " 133 " S-n-C3H, " " 134 " S—-n-C,Hgq " " 36-38 135 " benzylthio " " 136 " 3-trifluoro- = " " methyl-2- pyridylthio 137 " " H " - 75 - t.

Table 2 (cont'd)

Compound Melting » No. Rj 39) R3 Ry Point (°C) 138 CN 4-chlorophenyl- H ~N(CHj3), thio 139 1t S-n-C4H, " Hu 140 7" SC, Hg 1" 1t 141 " phenylthio phenylthio " 98-101 142 | n C,Hg n - 143 " benzene- H " sulfonyl 144 " 2-fluoro- " " benzenesulfon- yl 145 " 4-chlorobutyl Cl " 146 " 5-chloropentyl " " 147 " CH,OCH, " " 148 " CH,0C,H; " " 149 " 1-hydroxypropyl " " 150 " l1-hydroxybutyl " " 151 " benzyl " " 94-97 152 " 4-methylbenzyl " " : 153 " 3-methylbenzyl " " 154 " 2-methylbenzyl " " 155 " 2-fluorobenzyl " " 156 " phenethyl " " 157 " n-C3H, Br " 158 ”" n-C,Hg 1" " . —_ 76 —_

Table 2 (cont'd) ” Compound Melting

No. Rj " Rg R3 Rg Point (°C) 159 CN n-CcHy, Br -N(CH;), 160 " n-C.H, 4 " " l61l " iso-C3H, " " 162 " iso-C,H, " " 163 " cyclopropyl " " -- 164 " cyclohexyl "oo " 165 " 4~-chloro- " " phenylthio 166 " OCH,CF, " " 77-79 167 n S—-n-Cj3H, " " 168 1" S§-n-C,Hgq " " 169 " ~ S—iso-C,H, " " - 170 " CH,OCH, " " 171 " CH,0C,H, " " 172 " methoxycarbonyl " 173 " N-(4-~chloro- " " phenyl)carbamoyl 174 " N-phenyl- " " : carbamoyl 175 " N-ethyl- " " carbamoyl 176 -CSNH, C,H, cl " 177 N-acetyl- " " " thiocarba- moyl 178 -CSNH, n-C,H, " "

ad ed Table 2 (cont'd) y Compound Melting

No. Ry Ro R3 Ry Point (°C) 179 N-acetyl- n-C,Hg Cl -N(CHg), thiocarba- moyl 180 CN H I " 101-105 181 1" n-C3H, 7 1" 182 " " —COCF, " 183 ~CSNH, " Br " 184 N-acetyl- " " " thio- carbamoyl 185 -CSNH, " cl " 186 N-acetyl- " " " \ thiocarba- moyl 187 N-propion- " " " ylthio- carbamoyl 188 N-methyl- phenyl " " + thio- carbamoyl 189 N-acetyl- " " " thio- carbamoyl 190 CN -S0,N(CH;3), H " 142-149 191 " -Si(CHy), cl " 192 n n-C, oH, n " 193 n C,Hg H n : 194 " n-C,H, " " 195 " S-n-C,Hg 1" Ll} — 78 —_

pd a. } Table 2 (cont'd) »” Compound Melting

No. 1381 Ro Ra Ra Point (°C) 196 CN 1-hydroxy-3- Cl -N(CH;), phenylpropyl 197 " l-hydroxypropyl H " 198 " o-hydroxybenzyl C1 " 199 " a-acetoxybenzyl " " 200 " 1-hydroxy-3- " " . methylbutyl 201 " 4-methyl-3- on" " chlorophenyl 202 " 1" Br " 203 " 4-methoxy-3- Cl " chlorophenyl 204 ” ”" Br " 205 " 2,3-dichloro- Cl " - phenyl 206 " 4-ethoxyphenyl " " 207 0 n Br n 208 " 3,4-methylene- C1 " dioxyphenyl 209 ”" " Br " : 210 " 4-cyanophenyl C1 " 211 ”n ”" Br " 212 " 4-nitrophenyl Cl " 140-145 213 " 2-butenyl " " 214 " iso~Cg¢H,;, " " —_ 79 —

Table 2 (cont'd ; Compound Melting _ No.

Ri R2 Ry Rg Point (°C) 215 ~CSNH3 H Cl -N(CHj), 216 " CHj3 n " 217 " CsH,, " " 218 " benzyl " " 219 N-acetylthio-— H " " carbamoyl - 220 " CHj " n 221 " CsHyy " n 222 " benzyl n " 223 N-propionyl- " " " thiocabamoyl 224 —CSNH2 CaHs Br n 225 N-acetylthio- " n " - carbamoyl 226 N-propionyl- " " " thiocarbamoyl 227 CN 3-chlorobutyl Cl " 228 " —CF,CF=CF2 H " 229 " sec—CsHg Cl " 230 " _CHCH=C(CH3)2 " "

Table 2 (cont'd) yr | Compound Melting _ No.

Ry Ro _R3 Rg Point (°C) 3-b CN n-C5H, H -N(CHj), 51-52 9-b " SCH, " " 114-115 10-b " phenylthio " " 106-107 14-b " H Cl " 111-114 15-b " CH, " " 90-95 i6-b " n-C;H, " " 64-66 17-b " phenyl " " 109-112 18-b " 4-methylphenyl " " 133-134 19-b " 3~methylphenyl " " 20-b " 2-methylphenyl " " 93-96 21-b " 3,4-dimethyl- " " phenyl. . + 22-b " 4-methoxyphenyl " 23-a " 4-chlorophenyl " " 133-138 23-b " " " " 117-120 24-b " 2-chlorophenyl " " 113-117 25~b " 3,4-dichloro- - " " phenyl 26-b " 4-fluorophenyl n 120-122 27-b " SCH, " " 101-103 28-b " phenylthio " " 107-108 29-b " H Br " 100-103 30-b " CH, " " 107-110 0 31-b " tert-C,H, " "

Table 2 (cont'd) : Compound Melting

No. Ry Ry _R3 Rg Point : (°C) 32-b CN phenyl Br ~-N(CH3), 122-124 33-b * 4-methylphenyl " " 136-137 34-b " 4-tert-butyl- " " phenyl 35-b " 4-methoxyphenyl " " 36-b " | 4-fluorophenyl " " oo - 37-b " 4~chlorophenyl " " 39-b " C,Hg " " 112-115 : 40-b " -CH,CH=CH, " " 92-94 41-b " 4-bromophenyl Cl " 42-a " 4-isopropyl- " " 110-114 phenyl 42-b " " " " 135-138 43-b " 2-naphthyl " " 46-b " phenyl SCH, " 99-101 49-b —-CSNH, " H 50-b " 4-chlorophenyl " " 51-b Y phenyl Cl " 115-128 52-b " H Br " ’ 53-b " phenyl " " 110-118 : 55-b CN 3-methyl-4- Cl " 115-118 methoxyphenyl 56-b " 4-ethylphenyl " " 110-112 57-b " phenylthio Br " 94-97 ° - 82 - a pd

Table 2 (cont'd) . Compound Melting

No. Rj Ro Ry _ Rg Point (°C) 58-b CN benzyl Br -N(CH;), 87-89 59-b " 3-chloroproepyl H " 60-b " -S0,C, Hy " " 121-124 61l-b " 3-fluoropropyl C1 " 75-79 65-b " 2-chlorophenyl Br " 119-123 67-b " 4-(2',2',2'~ Cl " 111-113 - trifluoro- ethoxy)phenyl : . 68-b " " Br " 115-118 69-b " —-CH, 0H H " 106-107 70-b " 3-chlorophenyl C1 " 96-99 71-b " 3-fluorophenyl " " 72-b " 2-fluorophenyl " " ; 73-b " -SCH,CH=CH, H " 20-30 75-b " 1,2-diphenyl- " " 101-103 ethyl 76-b " o-hydroxybenzyl " " 98-100 103-b " phenyl © C1 -N(C,Hg), 99-101 ~ 104-b " " Br " 105-b " " Cl morpholino 106-b " " Br " 126-130 111-b " 4-chlorophenyl- Cl -N(CH;), 92-94 thio 112-b " 3-chloropropyl " oo" 102-105 ‘ 113-b " C,H, " " 95-97 119-b " n-C,Hgy " " 48-49

Table 2 (cont'd)

Compound Melting

No. _ RI Rp Ry Rg Point (°C) 120-b CN n-CgH,, Cl -N(CHy), 37-39 121-b " n-CGH, 5 " vw n2*%1.5002 23. 122-b " n-C,H,, " nw n?%°1.5019 23. 123-b " n-CgH, " vo n2¥%1 4081 124-b " n-C,,H,c oe " 34-36 125-b " iso-C3H, " " 75-82 (decomposed) 126-b " iso-C Hg " " 73-76 127-b " tert-C,Hg " " 74-80 128-b " cyclopropyl " " 76-79 . 129-b " cyclohexyl " " 107-111 130-b " -CH,CH=CH, " " 67-72 131-b " geranyl (C,gH,;) " " 132-b " SC,Hg " " 107-110 133-b " S-n-C3H, oo" " 70-74 134-b " S-n-C,Hg " " 135-b " benzylthio " " 149-152 136-b " 3-trifluoro- " " 126-127 methyl-2- pyridylthio 137-b " " H " 109-111 138-b " 4-chlorophenyl- " " 110-112 thio 140-a " SC,Hy " " 36-40 — 84 —_

Table 2 (cont'd) yr Compound Melting

No. R; Ro R3 Rg Point (°C) 140-b CN SC,H, H ~-N(CH;), 41-45 l42-a " phenylthio CoHg " 86-89 145-b " 4-chlorobutyl Cl " n2?t1.5382 146-b " 5-chloropentyl " " n2t-® 1.5328 147-b " CH,0CH, | " " 7 64-66 © 148-b " CH,0C, Hy " " 82-84 149-b " l-hydroxypropyl "oo 70-73 150-b " 1-hydroxybutyl " " ng* ?1.5097 151-b " benzyl " " 92-100 152-b " 4-methylbenzyl " " 125-129 ” 153-b " 3-methylbenzyl " " 93-96 154-b " 2-methylbenzyl " " 119-123 155-b " 2-fluorobenzyl " " 105-109 156-b " phenethyl " n 106-110 157-b " n-C5H, Br " 93-94 158-b " n-C,H, " " 159-b " n-CgH, , " " 160-b " N-CgH, 5 " " 99-101 161-b " iso-C4H, " " 162-b " iso-C, Hg " " 163-b " cyclopropyl " o 164-b " cyclohexyl " " - 85 - =n :

/

Table 2 (cont'd)

Compound Melting

No. Ry Ro R3 Rg Point (°C) 165-b CN 4-chlorophenyl- Br ~-N(CH;3), 94-95 thio l67-b " S-n-C3H, " " 76-78 168-b " S-n-C,Hq " " 48-50 169-b " S-iso-C,Hq " " 77-79 170-b " CH, OCH, " " 65-67 171-b " CH,OC, Hg E " 100-101 172-b " methoxycarbonyl " " 98-101 173-b " N-(4-chloro- " " 106-109 phenyl)carbamoyl 174-b " N-phenyl- " " 105-107 carbamoyl ’ ~ 175-b " N-ethyl- " " 98-101 carbamoyl 181-a " n-C;H, I " 76-79 181-b " " " " 99-103 182-a " " —-COCF, " 90-92 185-b —-CSNH, " a " 160-162 186-b N-acetyl- " " " 119-123 thio- : ’ carbamoyl 187-b N-propion- " " " 150-152 ylthio- carbamoyl . 188-b N-methyl- phenyl " " 67-72 thio- carbamoyl _ 86 —-—

yd rd Table 2 (cont'd) ~ Compound Melting

No. Rj Rp R3 _Rq4 Point (°C) 189-b N-acetyl- phenyl Cl -N(CH;), 110-114 thio- carbamoyl 191-b CN -Si(CHg); " " 116-119 1 H" 1" 23.6 192-b ' n-C, oH, np 1.4994 193-b " C,Hg H " 69-71 194-b " 1-C4Hg " " 52-53 © 195-b " S-n-C,Hy RE " 50-51 ' 24.0 196-b ! l1-hydroxy-3- Cl " np 1.5512 phenylpropyl 197-b " l1-hydroxypropyl H " 94-97 198-b " a-hydroxybenzyl Cl " 102-104 ~ 199-b " a—-acetoxybenzyl " " 82-86 200-b " 1-hydroxy-3- " " 71-74 methylbutyl 201-b " 4-methyl-3- " " 99-103 chlorophenyl 202-b * " - Br " 103-106 203-b " - 4-methoxy-3- C1 " 97-101 } chlorophenyl 204-b " " Br " 105-110 205-b " 2,3-dichloro- Cl " 103-107 phenyl 206-b " 4-ethoxyphenyl " no 122-124 207-b " " Br " 110-113 208-b " 3,4-methylene- Cl " 150-153 dioxyphenyl -— 87 —_

Table 2 (cont'd) compound Melting

No. Ry R2 Ry Ra Point : (°C) 209-b CN 3,4-methylene- Br ~N(CHj3), 95-98 dioxyphenyl 210-b " 4-cyanophenyl Cl " 182-185 211-b " " Br " 175-178 212-b " 4-nitrophenvl Cl " 144-146 213-b " 2-butenyl " " 87-90 214-b " iso-CgHy, " " 45-47 -218-b —~CSNH2 benzyl o " 118-121 © 222-b N-acetyl- " " " 163-165 thiocarbamoyl 223-b N-propionyl- " " " 149-152 thiocarbamoyl 227-b CN 3-chlorobutyl " " 54-57 230-b " ~CH,CH=C(CH3)2 " " 75-78 among the imidazole compounds of the present invention described in Table 2 above, the compounds having a mark "a" in their compound numbers are ones falling within the general formula (I-a) in the general formula (I) described hereinabove and the compounds having a mark "b" in their compound numbers are Ones falling within the general formula (I-b) in the general formula (I) described hereinabove.

The imidazole compounds of the present invention are useful as biocides for controlling harmful organisms in the agricultural, horticultural, medical, and pharma- ceutical areas.

re Bh

E As agricultural and horticultural fungicides, the compounds exhibit an excellent effect of controlling diseases of crop plants such as rice blast caused by

Pyricularia oryzae, rice sheath blight caused by

Rhizoctonia solani, oat crown rust caused by Puccinia coronata, cucum.er anthracnose caused by Colletotrichum lagenarium, cucumber powdery mildew caused by Sphaerotheca fuliginea, cucumber downy mildew caused by

Pseudoperonospora cubensis, tomato late blight caused by _ Phytophthora infestans, tomato early blight caused by

Alternaria solani, citrus melanose caused by Diaporthe _-citri, citrus common green mold caused by Penicillium digitatum, pear scab caused by Venturia nashicola, apple alternaria blotch caused by Alternaria mali, grape downy mildew caused by Plasmopara viticola, and further gray mold caused by Botrytis cinerea and sclerotinia rot caused by Sclerotinia sclerotiorum of various crops, etc.; or soil diseases caused by phytopathogenic fungi such as

Fusarium, Pythium, Rhizoctonia, Verticillium,

Plasmodiophora,_ Aphanomyces, etc.

In particular, the compounds exhibit an excellent effect of preventing deseases such as potato or tomato late blight caused by Phytophthora infestans, cucumber downy mildew caused by Pseudoperonospora cubensis, grape downy mildew caused by Plasmopara viticola, and tobacco blue mold caused by Peronospora tabacina; and - 89 -

Rr.

id

E soil diseases caused by phycomycetes such as’ plasmodiophora. Aphanomyces, pythium, etc.

The compounds of the present invention have a prolonged residual effect SO that they exhibit an excellent preventing effect, and further exhibit an ;/ excellent curative effect as well. Therefore, it is possible to control deseases by treatment after infection.

The compounds of the present invention are appropriate to pe applied to crop plants py foliar treatment. Further, the compounds possess a systemic activity so that it is also possible to control deseases of the stem and leaf by soil treatment. in addition, the compounds of the present invention show an excellent controlling effect against agriculturally and horticulturally harmful insects such as various planthoppeIsS;: diamondback moth (Plutella : xylostella). green rice leafhopper (Nephotettix cincticeps) adzuki bean weevil (Callosobruchus chinensis). common cutworm (Spodoptera litura), green peach aphid (Myzus persicae), etc.; mites such as two- spotted gpider mite (Tetranychus urticae), carmine spider mite (Tetranychus cinnabarinus), citrus red mite (Panonychus citri). etc.; and nematodes such as southern root-knot nematode (Meloidogyne incognita): etc.

Upon use; the compounds of the present invention can be prepared into a variety of forms of biocidal compositions such as emulsifiable concentrates, suspension concentrates, dusts, wettable powders, “aqueous solutions, y granules, etc., together with adjuvants, as in conventional formulations. Upon actual use of these formulations, they can be used as such or by diluting with a diluent such as water or the like to a predetermined concentration.

As the adjuvants used herein, mention may be made of carriers, emulsifying agents, suspending agents, dispersing agents, spreaders, penetrating agents, wetting - agents, thickeners, stabilizers, etc.

The carriers are classified into solid carriers and liquid carriers. As the solid carriers, mention may be made of animal and vegetable powders such as starch, sugar, cellulose powders, cyclodextrin, activated ~ charcoal, soybean powders, wheat powders, chaff powders, wood powders, fish powders, powdery milk, etc.; and mineral powders such as talc, kaolin, bentonite, bento- nite-alkylamine complex, calcium carbonate, calcium sulfate, sodium bicarbonate, zeolite, diatomaceous earth, white carbon, clay, alumina, silica, sulfur powders, etc.

As the liquid carriers, mention may be made of water; . animal and vegetable oils such as “corn oil, soybean oil, cotton seed oil, etc.: alcohols such as ethyl alcohol, ethylene glycol, etc.; ketones such as acetone, methyl ethyl ketone, etc.; ethers such as dioxane, tetrahydro- . furan, etc.; aliphatic hydrocarbons such as kerosene,

lamp oil, liquid paraffin, etc.; aromatic hydrocarbons ” such as xylene, trimethylbenzene, tetramethylbenzene, cyclohexane, solvent naphtha, etc.; halogenated hydro- carbons such as chloroform, chlorobenzene, etc. acid amides such as dimethylformamide, etc.; esters such as ethyl acetate, fatty acid glycerine esters, etc.; nitriles such as acetonitrile, etc.; sulfur-containing compounds such as dimethyl sulfoxide, etc.; and N-methyl pyrrolidone, etc.

The adjuvants other than the carriers described hereinabove, such as emulsifying agents, suspending agents, dispersing agents, spreaders, penetrating agents, wetting agents, thickeners, stabilizers, etc. are exemplified more specifically as following surfactants.

Polyoxyethylene alkylarylether, polyoxyethylene / glycol nonyl phenylether, polyoxyethylene laurylether, polyoxyethylene caster oil, polyoxyethylene alkylaryl sulfate (polyoxyethylene alkylphenyl ether sulfate), polyoxyethylene fatty acid ester (polyoxyethylene stearate), polyoxyethylene sorbitan fatty acid ester, lower alcohol phosphate, sodium alkylsulfate, sodium lignin sulfonate, calcium lignin sulfonate, alkylaryl sulfonate, sodium alkylbenzene sulfonate, sodium B8- naphthalene sulfonate-formaldehyde condensate, dialkyl- sulfosuccinate. - 92 -

Ba er ANOEIS pA RR 2s

The compound of the present invention is uniformly mixed with at least one kind of adjuvants described hereinabove to form a biocidal composition.

A weight ratio of the compound of the present invention to the adjuvants to be formulated is generally from 0.05:99.95 to 90:10, preferably from 0.2:99.8 to 80:20.

Since a concentration of the compound of the present invention to be applied may vary depending upon crop to be applied, method for application, / preparation form, dose to be applied, etc. , it is difficult to define a specific concentration range. However, if it is forced to define specifically, the concentration of the compound is generally from 0.1 to 10,000 ppm, desirably from 1 to 2,000 ppm in the case of foliar treatment, and is generally from 10 to 100,000 g/ha, desirably from 200 to 20,000 g/ha in the case of soil treatment.

Further, if necessary and desired, the compound of the present invention can be used as admixture with or in combination with other agricultural chemicals, for . example, insecticides, acaricides, nematocides, fungi- cides, antiviral agents, attractants, herbicides, plant growth regulators, etc. In this case, more excellent effects can sometimes be exhibited.

As the insecticides, acaricides or nematocides, mention may be made of, for example, organic phosphrous

Lo compounds, carbamate compounds, organic chlorine ’ compounds, organic metal compounds, pyrethroid compounds, benzoyl urea compounds, juvenile hormone-4 ike compounds, dinitro compounds, organic sulfur compounds, urea compounds, triazine compounds, etc. The compound of the present invention can also be used as admixture with or in combination with biological pesticides such as BT agents, insect pathogenic viral agents, etc. ] As . the fungicides, mention may be made of, for . example, organic phosphorus compounds, organic chlorine compounds, dithiocarbamate compounds, N-halogenothioalkyl compounds, dicarboximide compounds, benzimidazole compounds, azole compounds, carbinol compounds, benz- anilide compounds, acylalanine compounds, pyridinamine } compounds, piperazine compounds, morpholine compounds, anthraquinone compounds, quinoxaline compounds, crotonic acid compounds, sulfenic acid compounds, urea compounds, , antibiotics, etc.

On the other hand, as medical and pharmaceutical antimicrobial agent, the compounds of the present invention are effective against microorganisms belonging to Staphylococcus and Trichophyton.

Upon use, the compounds can be orally and unorally administered similarly to the conventional medicines.

In the case of oral administating use, the compounds may be formulated into various types suited for pd gastroenteral absorption such as tablets, granules, capsules, syrup, aqueous or oily suspensions, and the like.

And, in the case of unoral administrating use, compounds may be formulated for injection or into various types suited for cuteneous absorption such as creams, ointments, and the like.

Preferable dose varies according to the conditions such as etat, age, etc. of human beings and animals . infected with pathogen. }

Hereafter, test examples of the biocidal composi- tions for controlling harmful organisms in the agri- cultural, horticultural, medical, and pharmaceutical areas in accordance with the present invention are described below. ) Standards for evaluation of the agricultural and horticultural fungicides follow the following criteria for ‘ evaluation, unless otherwise indicated.

Standards for Evaluation

The controlling effect was determined by visually observing a degree of desease of a test plant and expressed by the following 5 grades of the index of } control. {Index of Control] [Dégree of Desease] 5: No lesion is noted at all. - 95 -

EA icc. fi hs ot sas Ee ge

A

. pd 4: Area, number Or length of lesions is y less than 10% as compared to the non- } treated plot. 3: Area, number or length of lesions is less than 40% as compared to the non- treated plot. 2: Area, number Or length of lesions is less than 70% as compared to the non- treated plot. : ) ol: Area, number or length of lesions is more than 70% as compared to the non- . treated plot. : Test Example 1 - Test on preventive effect against cucumber powdery mildew ’ Cucumber (cultivars: Suyo) was cultivated in a polyethylene pot having a diameter of 7.5 cm. When cucumber reached the one-leaf stage, 10 ml of a solution obtained from each of test compounds adjusted to a predetermined concentration was sprayed over cucumber . using a spray gun. After keeping the pots in a constant : temperature chamber of 22 to 24°C over one day and one night, conidia of fungi of powdery mildew (Sphaerotheca fuliginea) were inoculated. Ten days after the inoculation, an area of lesion on the first leaf was investigated, and an index of control was determined by the standards for evaluation described above. The results r shown in Table 3 were obtained.

Table 3

Index of Control

Compound No, 500 ppm 15-b 4 23-a 4 , 59-b | 4 106-b : 3 - 133-b 4 167-b 3 169-b 3 171-b 5

Test Example 2

Test on preventive effect against cucumber anthracnose - Cucumber (cultivars: Suyo) was cultivated in a polyethylene pot having a diameter of 7.5 cm. When cucumber reached the two-leaf stage, 10 ml of a solution obtained from each of test compounds adjusted to a predetermined concentration was ‘sprayed over cucumber using a spray gun. After keeping the pots in a constant } temperature chamber of 22. to 24°C over one day and one night, a spore suspension of fungi of anthracnose (Colletotrichum lagenarium) was inoculated. Seven days after the inoculation, an area of lesion on the first leaf was investigated, and an index of control was determined

» * by the standards for evaluation described above. The results shown in Table 4 were obtained.

Table 4

Index of Control

Compound No. 500 ppm 3-b 3 . 17-b 3 26 5 28-b 3 : 51 3 51-b 3 . 59-b 3 ] 69-b 3 70-b 4 73-b 3 75-b 3 101 4 105 4 106 3

Test Example 3

Test on preventive effect against cucumber downy mildew . Cucumber (cultivars: Suyo) was cultivated in a polyethylene pot having a diameter of 7.5 cm. When cucumber reached the two-leaf stage, 10 ml of a solution obtained from each of test compounds adjusted to a predetermined concentration was sprayed over cucumber using a spray gun. After keeping the pots in a constant - 98 - a ny rd : | temperature chamber of 22 to 24°C over one day and one night, a spore suspension of fungi of downy mildew (Pseudoperonospora cubensis) was inoculated. six days after the inoculation, an area of lesion on the first leaf was investigated, and an index of control was determined by the standards for evaluation described above. The results shown in Table 5 were obtained.

Table 5

Index of Control Index of Control

Compound No. 125 ppm 31 ppm Compound No. "125 ppm 31 pom ppm 4 5 5 29-b 5 5 5 5 30-b 5 5 6 5 4 31 4 3 7 5 5 32-b 5 5 8 5 3 33 - 5 - 14-b 5 3 34 5 5 15-b 5 5 36 - 5 16-b - 5 37 5 5 17 5 5 45 5 5 17-b ~ 5 47 5 5 © 23 5 5 48 5 5

Table 5 (cont'd)

Index of Control Index of Control

Compound No. 125 ppm 31 ppm Compound No. 125 ppm 31 ppm 49 5 4 © 101 5 4 50 5 5 103 5 5 52 5 5 105 4 - 53-b 5 5 106 5 5

Test Example 4

Test on curative effect against cucumber downy mildew : Cucumber (cultivars: Suyo) was cultivated in a ~ polyethylene pot having a diameter of 7.5 cm. When cucumber reached the two-leaf stage, a spore suspension of fungi of downy mildew (Pseudoperonospora cubensis) was inoculated. Six hours after the inoculation, 10 ml of a solution obtained from each of test compounds adjusted to - a predetermined concentration was sprayed over cucumber using a spray gun. After keeping the pots in a constant temperature chamber of 22 to 24°C for 6 days, an area of lesion on the first leaf was investigated, and an index of control was determined by the standards for evaluation described above. The results shown in Table 6 were obtained.

Table 6

Index of Control Index of Control

Compound No. 125 ppm 31 ppm Compound No. 125 ppm 31 ppm 3-b 5 - 8 5 -

Co»

Table 6(cont'd)

Index of Control : Index of Control

Compound No. 125 ppm 31 ppm Compound No. 125 ppm 31 ppm 9-b 5 - . 32-b 5 - 10-b 5 - 33 5 - 12 5 ~ 33-b 5 - 14-b 5 - 36 5 - 15-b 5 - 37 5 - : l6-b 5 - 39-b - 5 ~17 5 - 40-b - 5 ~~ 17-b 5 - 41 - 5 18 - 5 46-a 5 - 18-b 5 = 48 4 - 19 5 - . 51 5 - 20-b 5 - 51-b 5 - - 22 5 = 52 5 - 23 5 - 53-b 5 - . 23-a 5 - 56-b 5 - 23-b 5 - 57-b ~ 5 24-b - 5 58-b - 5 - 4 59-b - 5 26 - 5 60-b - 5 - 26-b 5 - 61-b - 5 27-b 5 - 65-b 5 - 28-b 5 - 67-b 5 - 29-b 5 - 68-b = 4 30-b | 5 - 69-b 4 -

ror Table 6 (cont'd)

Index of Control Index of Control

Compound No. 125 ppm 31 ppm Compound No. 125 ppm 31 ppm 70-b 5 ~ 138-b = 5 72 = 5 141 4 - 74 - . 4 142-2 5 5 76-b 5 - 145-b - 5 88 - 5 146-b - 5 101 4 - 147-b 5 5

A03-b 5 - 148-b 5 5 106-b 5 - 149-b - 5 111-b - 5 150-b 5 - ~ 112-b 5 5 151 - 5 113-b 5 5 151-b 5 5 119-b 5 5 152-b ~ 3 120-b 5 5 153-b - 5 121-b 5 5 154-b - 5 125-b - 5 155-b - 5 ) 126-b - 5 156-b - 5 128-b - 5 157-b - 5 129-b - 5 160-b 5 5 130-b 5 5 166 5 3 7 132-b - 5 167-b 5 5 133-b 5 4 169-b 5 5 134 5 5 170-b 5 5 135-b 4 - 171-b 5 5 136-b - 3 173-b 4 - - 102 - a. me AONE VINIPTIY FT, TNE 150

F Sad

Table 6 (cont'd)

Index of Control Index of Control

Compound No. 125 ppm 31 ppm Compound No. 125 ppm 31 ppm 180 5 ~ 201-b 4 ~ 181-a - 5 203-b 3 - 181-b - 5 208-b 4 3 185-b - 5 209-b 5 - 186-b - 5 210-b 4 - 187-b - 5 212-b 5 5 189-b 5 5 213-b - 5 190 © 5 4 214-b - 5

Test Example 5

Test on systemic effect against cucumber downy mildew

Cucumber (cultivars: Suyo) was cultivated in a . polyethylene pot having a diameter of 7.5 cm. When cucumber reached the two-leaf stage, 15 ml of a solution obtained from each of test compounds adjusted to a predetermined concentration was drenched on the surface of soil using a pipette. After keeping the pots in a constant temperature chamber of 22 to 24°C for 2 days, a spore suspension of fungi of downy mildew (Pseudoperonospora cubensis) was inoculated. Six days after the inoculation, an area of lesion on the first leaf was investigated, and an index of control was determined by the standards for evaluation described above. The results shown in Table 7 were obtained.

Table 7

Index of Control

Compound No. 500 ppm 125 ppm 1 5 3 14-b 5 5 15-b - 5 17 5 4 29-b 5 5 : 30-b 5 5 37 5 5 52 5 5 53-b 5 5

Test Example 6

Test on preventive effect against tomato late blight

Tomato (cultivars: Ponderosa) was cultivated in a polyethylene pot having a diameter of 7.5 cm. When tomato reached the four-leaf stage, 10 ml of a solution obtained from each of test compounds adjusted to a predetermined } concentration was sprayed over tomato using a spray gun.

After keeping the pots in a constant temperature chamber i of 22 to 24°C over one day and one night, a zoosporangium suspension of fungi of late blight (Phytophthora infestans) was inoculated. Five days after the inoculation, an area of lesion on the leaves was investigated, and an index of control /was determined by ww on the standards for evaluation described above. The results shown in Table 8 were obtained.

Table 8

Index of Control

Compound No. 125 ppm 31 ppm 8 ppm 3-b - 5 - 4 5 4 - 5 5 - 6 5 4 - - 7 5 - 5 - 8 5 5 - 9-b - 5 - 10-b - - 5 12 , - 5 3 14-b - 5 - 15-b - 4 - 16-b - 5 4 17 5 5 - 17-b 5 5 = . 18 - 5 - 18-b - 5 - : 19 - 5 - 20-b - 5 - 21 - 5 -

J

Table 8 (cont'd)

Index of Control

Compound No. 125 ppm 31 ppm 8 ppm 22 - 5 = 23 5 5 - 23-a ~ 5 ~ 23-b - 5 - 24-b - 5 5 - 5 5 - 26 - 5 - 26-b - 5 - 27-b = 5 - 28-p - 5 - 29-b 5 5 = 30-b - 5 - ” 32-b 5 5 - 33 5 5 ‘ - 33-b - 5° - 34 4 4 - : 36 5 5 - 37 - 5 - 39-b = - 5 40-b - 5 5 41 - 5 5 : © 42-a - 5 - 42-b - 5 - 43 - - 5

Pd | ’

Table 8 (cont'd)

Index of Control

Compound No. 125 ppm 31 ppm 8 ppm 45 5 5 - 46-a 5 5 - 48 5 5 - 49 5 3 ~ 50 4 - - 51 5 5 - - 51-b 5 5 - 52 5 4 - 53-b 5 5 - 55-b - 4 5 56-b - 5 - 57-b - - 5 - 58-b - 5 5 59-b - - 5 60-b - 5 - ~ 61-b - 5 5 65-b - 5 - 66 5 5 - 67-b - - 5 68-b - - 5 70-b - - 5 72 - - 5 73-b - 4 - 74 - - 5 pd pd Table 8 (cont'd) index of Control

Compound No. i25 ppm 31 ppm 8 ppm 75-b - 5 - 76-b - 5 - 84 = - 5 88 - - 5 101 5 5 - 103 5 - - - 104 5 4 - 105 5 4 - 106-b 5 4 - 111-b - - 4 112-b - 5 5 113-b - - 5 - ~ 114 - 5 5 119-b - 5 5 120-b - 5 5 : 121-b - 5 5 122-b - 5 5 123-b - 5 5 124-b - 5 5 125-b - - 5 ~ 126-b - - 5 128-b - 5 4 129-b = 5 5 © 130-b - 5 5 a. “4 pd

Table 8 (cont'd)

Be Index of Control ol Compound No. 125 ppm 31 ppm 8 ppm i 132-b ~ 5 5 133-b ~ - 5 134 ~ 5 5 135-b ~ 5 5 136-b - - 5 137-b - ~ 5 : 138-b - = 4 141 - 5 5 y 142-a ~ 5 5 145-b ~ - 4 146-b - 5 5 147-b - 4 3 = 148-b - 4 - : 149-b - - 5 151 - - 5 3 : | 151-b - 5 5 4 152-b - - 5

XS

E 153-b - _ 5 #3 5 154-b - - 5 oS 155-b - - 5 ; 156-b - ~ 5

E 157-b - ~ 5 i

J yd Table 8 (cont'd) / Index of Control

Compound No. 125 ppm 31 ppm 8 ppm 160-b - 5 5 166 - 5 3 167-b - 5 5 169-" - 5 5 170-b - 5 3 171-b - 5 - - 173-b - 4 3 174-b - 4 - 180 - - 5 181-b ~ 5 5 182-b - 5 5 185-b - - 5 - 186-b - - 5 187-b - - 5 189-b - 5 4 190 - 4 - 201-b - 5 5 202-b - 5 5 203-b - 4 5 205-b - - 5 © 206-b - 5 5 207-b - 5 - 208-b - 5 5

* pr ed ie - } re oo Table 8 (cont'd)

Index of Control

Compound No. 125 ppm 31 ppm 8 ppm 209-b - 4 - 210-b = 4 3 211-b - 4 - 212-b - . 5 3 213-b - 5 5 i 214-b - 5 5 ” / Test Example 7 :

Test on systemic effect against tomato late blight

Tomato (cultivars: Ponderosa) was cultivated in a polyethylene pot having a diameter of 7.5 cm. When tomato reached the four-leaf stage, 15 ml of a solution obtained - from each of test compounds adjusted to a predetermined concentration was drenched on the surface of soil using a pipette. After keeping the pots in a constant temperature chamber of 22 to 24°C for 2 days, a =zoosporangium suspension of fungi of late blight (Phytophthora infestans) was inoculated. Five days after the . inoculation, an area of lesion on the leaves was investigated, and an index of control was determined by the standards for evaluation described above. The results shown in Table 9 were obtained. :

pag - pg eo Nd 5 oer on ig

Table 9

Index of Control compound NO. 500 ppm 125 ppm 3-b - 4 ~10-b 5 5 16-b - 4 17-b 5 4 al 19 4 4 ; 20-b 5 4 ; 22 5 4 4 . 27-b 5 5 28-b 5 - ! \ 40-b 5 5 qi 51 5 5 51-b 5 5 i a 57-b - 4 a. 58-b 5 3 - B 59-b - 4

A

™ 76-b - 5 fs 1 rest Example 8 i Test ON preventive effect against rice blast o Rice plant (cultivars: Chukyo© pasahi) was es. cultivated in a polyethylene pot having a diameter of 7.5

EAE ai cm. When rice plant reached the gour—leaf stage, 20 ml of hg a solution obtained from each of test compounds adjusted to a predetermined concentration was sprayed over rice oA plant using @ spray gun. nfter keeping the pots in a

NT . constant temperature chamber of 22 to 24°C over one day and one night, a spore suspension of fungi of blast (Pyricularia oryzae) was inoculated. Five days after the inoculation, a number of lesion was investigated, and an index of control was determined by the standards for evaluation described above. The results shown in Table 10 were obtained. .

Table 10 ~ Index of Control

Compound No. . 500 ppm 27-b 4 48 3 53-b 3 55=b 4 134 3 - 167-b 3 201-b 4 202-b 4

Test Example 9 i : Test on preventive effect against rice sheath blight

Rice plant (cultivars: Chukyo Asahi) was cultivated in a polyethylene pot having a diameter of 7.5 cm. When rice plant reached the five-leaf stage, 20 ml of a solution obtained from each of test compounds adjusted to a predetermined concentration was sprayed over rice plant using a spray gun. After keeping the pots in a constant temperature chamber of 22 to 24°C over one day

: SN ~~. and one night, rice straw in which fungi of sheath blight (Rhizoctonia solani) had been previously incubated was set between leaf sheath portions to inoculate. After keeping the pots in an inoculation room having a temperature of 28°C and a humidity of 100% for 5 days, a length of lesion was investigated, and an index of control was determined by the standards for evaluaticn described above. The results shown in Table 11 were obtained.

Table 11 : index of Control : Compound No. 500 ppm 6 3 21 3 27-b 3 34 3 : | 51-b 3 53-b 3 104 3

Test Example 10

Test on preventive effect against oat crown rust oo Oats (cultivars: Zenshin) were cultivated in a polyethylene pot having a diameter of 7.5 cm. When oats reached the two-leaf stage, 10 ml of a solution obtained from each of test compounds adjusted to a predetermined concentration was sprayed over oats using a spray gun.

After keeping the pots in a constant temperature chamber of 22 to 24°C over one day and one night, conidia of fungi

Ed Cy of crown rust (Puccinia coronata) were inoculated. Ten days after the inoculation, an area of lesion on the second leaf was investigated, and an index of control was determined by the standards for evaluation described above. The results shown in Table 12 were obtained.

Table 12

Index of Control

Compound No. 500 ppm 4 3 - 14-b 3 44 4 52 4 59-b 3 : 104 4 172-b 4 180 5 190 3

Test Example 11

Test on preventive effect against turnip clubroot

Soil contaminated with fungi of clubroot (Plasmodiophora brassicae) was filled in a 1/14,000 a (1/140 m?) pot, and 20 ml of a solution obtained from each of test compounds adjusted to 4 kg/10 a ‘and 1 kg/10 a calculated as the active ingredient was drenched on the surface of the soil using a pipette. One day after treatment, the soil was mixed over the whole layers, and turnip (cultivars: Kanamachi Kokabu) was seeded. The turnip was grown in a greenhouse. Thirty days after the seeding, a degree of clubroot formation was investigated, and an index of control was determined by the standards for evaluation described below. The results shown in

Table 13 were obtained.

Standards for Evaluation [Index of Control] [Degree of Occurrence of Clubroot] 5: formation of clubroot : none . 4: " : slight 3: no : medium 2: " : many 1: " : abundant

Table 13

Index of Control

Compound No. 4 kg/10 a 1 kg/l0 a 1 5 ~ 4 4 - 5 5 6 5 5 7 5 5 8 5 5 : 9-b 5 4 10-b - 5 12 - 5 14-b 5 5 15-b ~ 5 16-b 5 5 - 17 - 5 17-b - 5 18 5 5 18-b - 5 19 5 5 20-b 5 4 21 5 5 22 5 5 23 5 5 23-a - 4 23-b - 4 24-b - 5

. Table 13 (cont'd)

Index of Control

Compound No. 4 kq/10 a 1 kq/10 a 26 5 4 26-b - 5 27-b 5 5 29-b - 5 30-b = 5 32-b - 5 - 33 5 5 33-b - 5 34 5 5 36 5 5 37 5 5 39-b - 5 - 40-b - 5 42-a - 5 42-b - 5 46-a 5 - 49 - 4 50 5 5 - 51 5 5 51-b 5 5 52 - 5 53-b 5 4 55-b - 5 56-b - 5

Table 13 (cont'd) __Index of Control _

Compound No. 4 kg/10 a 1 kg/10 a 58-b - 5 59-b 5 5 65-b - 5 67-b = 5 68-b - 5 73-b 4 - - 88 = 4 105 4 ~ 106 5 = 180 5 5 201-b - 5 202-b - 5 206-b - 5 207-b - 5

Test Example 12

Antimicrobial test (phytopathogenic fungi)

Mycelial disc (agar punching) of preincubated

Pythium aphanidermatum was transplanted on potato-dextrose agar medium (PDA medium) containing 100 ppm of streptomycin and 100 ppm of each of test compounds. After incubation at 22°C for 48 hours, a diameter of mycelium was measured. Inhibition of hyphal growth (%) was determined by the following equation. The results shown in Table 14 were obtained.

\ hibition of hyphal growth (G6)= 100 — —— 2 ameterof mycelium treated PO - . Diameterof mycelium innon— treated plot

Table 14

Inhibition of

Compound No. Hyphal Srowtn 3-b 100 95 7 100 9-b 100 ) 10-b © 100 14-b 100 15-b 100 16-b 100 17 100 17-b 100 . 23 100 27-b 100 28-b 100 29-b 100 30-b 100 31 100 33 100 i . fi v 26182 “i A

Table 14 (cont'd)

Inhibition of

Compound No. ~~ _ Hyphal Growth (%) 34 100 36 100 37 100 45 100 49 100 53-b 100 101 } 100 103 100 104 100 105 100 : 106 100 180 100

Test Example 13

Miticidal test on adults of two-spotted spider mites

Kidney bean (cultivars: Edogawa Saito) was . cultivated in a polyethylene pot having a diameter of 7.5 cm. When kidney bean reached the primary leaf stage, one primary leaf was left, and other leaves were cut out.

After infesting about 30 adults of two-spotted spider mite (Tetranychus urticae: resistant to Dicofol and organic phosphorus insecticides), the seedlings were immersed in ml of a solution obtained from each of test compounds adjusted to a predetermined concentration for about 10

F on seconds. After drying, the seedlings were allowed to stand in a constant temperature chamber of 26°C with lighting. Two days after releasing the mites, numbers of dead mites were investigated, and a mortality (3%) was determined by the following equation. The results shown in Table 15 were obtained.

Mortality (= —wocrofdoad mites, 0

Number of released mites

Table 15 : Mortality (%)

Compound No. 800 ppm 200 ppm 9-b 100 100 10-b 100 100 14-b 100 100 15-b 100 100 23 100 100 23-a 100 - 23-b 91 - 26-b | 100 - 29-b 100 100 36 100 100 40-b 100 100 41 100 - 52 100 100 »

Table 15

Mortality (s)

Compound No. 800 ppm 200 ppm 57-b 100 - 58-b 100 - 72 100 - 88 100 - 101 100 100 112-b 100 - - 113-b 100 100 119-b 100 100 133-b 100 90 151-b 100 - 167-b 100 87 169-b 100 100 - 172-b 100 = 205-b 100 -

Test Example 14

Ovicidal test on two-spotted spider mites . Kidney bean with only ‘one primary leaf was transplanted on a polyethylene pot. After infesting i adults of two-spotted spider mite (Tetranychus urticae) and ovipositing for 24 hours, the adults were removed.

Then, the kidney bean described above was immersed in 20 ml of a solution obtained from each of test compounds adjusted to a Predetermined concentration for about 10 seconds. After drying, the kidney bean was kept in a constant {emperature chamber of 26°C with lighting. Five r to seven days after the treatment, a state of hatching was investigated, and an ovicidal rate (%) was determined by the following equation. The results shown in Table 16 were obtained. Death immediately after hatching was regarded to be ovicidal.

Ovicidal Rate (%)= _ Numberofkilled eggs _, gg

Number of oviposited eggs

Table 16

Oovicidal Rate (%)

Compound No. 800 ppm 10-b 100 15-b 100 26-b 100 29-b 100 - 30-b 70 40-b 100 52 98 i 57-b 90 88 100 101 100 113-b 100 , 119-b 100 133-b 100 167-b 100 169-b 100 194A -—

Test Example 15

Insecticidal test on small brown planthoppers

Young seedlings of rice plant were immersed in 20 ml of a solution obtained from each of test compounds adjusted to a predetermined concentration for about 10 seconds. After drying, the root was wrapped with wet absorbent cotton and put in a test tube. Then, 10 larvae of second to third instar of small brown planthoppers (Laodelphax striatellus) were released in the test tube, . and the opening of the test tube was covered with gauze.

The test tube was kept in a constant temperature chamber of 26°C with lighting. Five days after the release of the larvae, numbers of dead insects were investigated, and a mortality rate (%) was determined by the following equation. The results shown in Table 17 were obtained.

Mortality (%)= Number of dead insects %100

Number of released insects

X oo

Table 17 mortality (%) compound NO. g00 ppm 200 ppm 14-b 100 100 15-b 100 80 40-b 100 - 113-b 100 - , 119-Db 100 - - 133-b 100 - ~1s51-b 100 -

Test Example 16

Insecticidal rest on green peach aphids

A piece of cabbage leaf was immersed in 20 ml of a solution obtained from each of test compounds adjusted to : a predetermined concentration for about 10 seconds; followed by drying. wet filter paper’ was put on & petri ] dish naving a diameter of 9 cm, and the air-dried leaf piece was put thereon. Apterous viviparous females of green peach aphids (Myzus persicae) were released on the leaf. The petri dish was covered and kept in a constant temperature chamber of 26°C with lighting. Two days after release of the insects, numbers of dead insects Were investigated: and a mortality (3) was getermined in the same manner as Test Example 15 described above. The results shown in Table 18 were obtained.

re

Table 18

Mortality (3%)

Compound No. 800 ppm 1 70 32-b 70 52 90

Test Example 17

Insecticidal test on common cutworms

A piece of cabbage leaf was immersed in 20 ml of a solution obtained from each of test compounds adjusted to a predetermined concentration for about 10 seconds followed by drying. Wet filter paper was put on a petri dish having a diameter of 9 cm, and the air-dried leaf piece was put thereon. Second to third instar larvae of common cutworms (Spodoptera litura) were released on the - leaf. The petri dish was covered and kept in a constant temperature chamber of 26°C with lighting. Five days after release of the larvae, numbers of dead insects were investigated, and a mortality (3%) was determined in the

Same manner as Test Example 15 described above. The results shown in Table 19 were obtained. - 127 - _ ;

— ®

Table 19

Mortality (%)

Compound No. 800 ppm 26-b | 100 40-b 100 67-b 100 68~b 100 72 100 74 100 = Test Example 18Antimicrobial test (fungi)

Trichophyton metagrophytes and Trichophyton rubrum were inoculated on Sabouraud agar medium containing 10 ppm of kanamycin and each of test compounds. After incubation at 28 to 30°C for 5 days, growth of text fungi was - examined. As the results, Compound Nos. 25, 34, 55-b, : 119-b, and 168-b were effective against Trichophyton metagrophytes, and Compound No. 23 was effective against

Trichophyton rubrum. Compound Nos. 26, 120-b, 134, and 169-b were effective against both fungi.

_ EE

Test Example 19

Antimicrobial test (bacteria)

Staphylococcus aureus was inoculated on bouillon agar medium containing 10 ppm of each of test compounds.

After incubation at 37°C for 16 hours, growth of test bacteria was examined. As the results, Compound Nos. 17, 20-b, 21, 22, 23, 25, 26, 26-b, 28-b, 33, 34, 37, 41, 42- a, 43, 57-b, 67-b, 103, 104, 105, 106, 134, 168-b, 201-b, 202-b, 203-b, and 205-b were effective. . Formulation examples of the present invention are described below, but the compounds, dose in formulatioLns, type of formulations, etc. in the present invention are not deemed to be limited to those described below.

Formulation Example 1 (Wettable powder) (a) Compound No. 5 50 parts by weight (b) Kaolin 40 " (c) Sodium lignin sulfonate 7 " (d) Dialkylsulfosuccinate 3 "

The above components are uniformly mixed.

Formulation Example 2 (Wettable powder) ’ (a) Compound No. 17-b 20 parts by weight (b) Kaolin 72 " (c) Sodium lignin sulfonate 4 " (d) Polyoxyethylene alkylaryl 4 " ether

The above components are uniformly mixed.

Formulation Example 3 (Wettable powder) ’ . (a) Compound No. 18-b 6 parts by weight (b) Diatomaceous earth 88 " (c) Dialkylsulfosuccinate 2 " (d) Polyoxyethylene alkylaryl 4 " sulfate

The above components are uniformly mixed.

Formulation Example 4 (Wettable powder) (a) Kaolin 78 parts by weight - (b) Sodium B-naphthalene- 2 " : sulfonate-formaldehyde condensate (c) Polyoxyethylene alkylaryl 5 " sulfate (d) Fine silica 15 "

A mixture of the above components and Compound No. 22 are mixed in a weight ratio of 4:l.

Formulation Example 5 (Wettable powder) (a) Compound No. 16-b 10 parts by weight (b) Diatomaceous earth 69 " (c) Calcium carbonate powder 15 " (d) Dialkylsulfosuccinate 1 " (e) Polyoxyethylene alkylaryl 3 " sulfate (£) Sodium B-naphthalene- 2 " sul fonate-formaldehyde condensate

The above components are uniformly mixed.

Formulation Example 6 (Wettable powder) (a) Compound No. 17-b 20 parts by weight - 130 -

APT Fiighic. HoH hip (HE one VET re Re ala Lo RRR

RE WL Cr ee Taghen Coe } EERE Ra fd aie LR Te Shen eb RIA Sr al te

- Rn (b) Kaolin 62.4 " r (c) Fine silica 12.8 " (d) Alkylaryl sulfonate 1.6 " (e) Polyoxyethylene alkylaryl 2.4 " sulfate (£) Polyoxyethylene alkylaryl 0.8 " ether

The above components are uniformly mixed.

Formulation Example 7 (Dust) (a) Compound No. 23 5 parts by weight (b) Talc 94.5 " (c) Lower alcohol phosphate 0.5 "

The above components are uniformly mixed. © Formulation Example 8 (Dust) (a) Compound No. 16-b 0.2 parts by weight (b) Calcium carbonate powder 98.8 " (c) Lower alcohol phosphate 1.0 "

The above components are uniformly mixed.

Formulation Example 9 (Emulsifiable concentrate) (a) Compound No. 26 20 parts by weight (b) Xylene 60 " (c) Polyoxyethylene alkylaryl 20 " ether

The above components are mixed and dissolved.

Formulation Example 10 (Suspension concentrate) (a) Compound No. 151 10 parts by weight (b) Carn oil 77 " (c) Polyoxyethylene caster oil 12 "

7@ A (d) Bentonite-alkylamine 1 " complex [ The above components are uniformly mixed and pulverized.

Formulation Example 11 (Granule) (a) Compound No. 33-b 1 parts by weight (b) Bentonite 61 " (c) Kaolin 33 " (d) Sodium lignin sulfonate 5 " ’ A suitable amount of water required is added to the above components, followed by mixing and granulating.

While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without ) departing from the spirit and scope thereof. - 132 - am 4 .

w 26 los

Ty

LF 8 +5

ABSTRACT OF THE DISCLOSURE po o 22

A compound as an intermediate represented by N i the following general formula (I1'): < 3

N—__R2 od I (I1")

N Rg

H wherein Ry and Rg each represents a hydrogen atom; a halogen atom; a nitro group; a Cyano group; a trimeth- ylsilyl group; a Cz_g cycloaikyl group; a naphthyl group; a Cig alkyl group which is. optionally substituted with one or more halogen atoms, hydroxyl A groups, acetoxy groups, Ci-a alkoxy groups, halggenated

Cy-4 alkoxy groups, phenyl groups, halogenated phenyl groups, or Cj_4 alkylated phenyl groups; a C2-10 alkenyl group which is optionally substituted with one or more /halogen atoms; a Cj.g alkoxy group which is optionally : substituted with one or more halogen atoms; a phenyl group which is optionally substituted with one or more halogen atoms, C;_4 alkyl groups, halogenated Cj_4 alkyl groups, Cy_y alkoxy groups, halogenated Cj_4 alkoxy groups,

C1-4 alkylthio groups, halogenated Cj.4 alkylthio groups,

nitro groups, cyano groups, or 3,4-methylenedioxy groups; a furyl group which is optionally substituted with one or more halogen atoms or Cj_4 alkyl groups; a thienyl group which is optionally substituted with one or more halogen atoms or Cy_4 alkyl groups; a pyridyl group which is optionally substituted with one or more halogen atoms or

Cia alkyl groups; an -SO,R; group, wherein R, represents a Cy.g alkyl group, a Cy_¢ alkenyl group, a phenyl group which is optionally substituted with one or more halogen atoms, a benzyl group, a pyridyl group which is optionally substituted with one or more halogen atoms, Cy_, alkyl groups, or halogenated Cj_4 groups; or an -NRs Rg group, wherein Rg and Rg each represents a Cy_4 alkyl group, and n is 0, 1, or 2; or a -~CONH)R, group, wherein Rig represents a C;_4 alkyl group which is optionally substituted with one or more halogen atoms, a

C1.4 alkoxy group which is optionally substituted with one or more halogen atoms, or a phenyl group which is optionally substituted with one or more halogen atoms; and m is O or 1.

\ nitro groups, cyano groups, or 3,4-methylenedioxy groups; a furyl group which is optionally substituted with one or more halogen atoms or Cj_, alkyl groups; a thienyl group which is optionally substituted with one or more halogen atoms or Cy_4 alkyl groups; a pyridyl group which is optionally substituted with one or more halogen atoms or

Cia alkyl groups; an -S0,R7 group, wherein R, represents a Cj.g alkyl group, a Cy. alkenyl group, a phenyl group which is optionally substituted with one or more halogen atoms, a benzyl group, a pyridyl group which is optionally ’ substituted with one or more halogen atoms, C;_, alkyl groups, or halogenated C;_4 groups; or an -NR¢ Rg group, wherein Rg and Rg each represents a Cj_4 alkyl group, and n is 0, 1, or 2; or a -CO(NH)R, group, wherein Rio represents a Cy_, alkyl group which is optionally substituted with one or more halogen atoms, a

Cy.4 alkoxy group which is optionally substituted with one or more halogen atoms, or a phenyl group which is optionally substituted with one or more halogen atoms; and m is O or 1.

Cer,

Claims (1)

C192 AMENDED CLAIM :

1. A compound as an intermediate represented by the follewing general formula (11'): wl > H wherein R, and Ry each represents a hydrogen atom; a halogen atom; a nitro group; a cyano group; a trimethyl- gilyl group; A Cz_g cycloalkyl group; a naphthyl group; a Ci_12 alkyl group which is optionally substituted with one or more halogen atoms, hydroxyl groups, acetoxy groups, Ci_n alkoxy groups, halogenated Cig alkoxy groups, phenyl groups, halogenated phenyl groups, or Cin alkylated phenyl groups; 8 Cs_10 alkenyl group which is optionally substituted with one or more halogen atoms; A Cy ¢ plkoxy group which is optionally subs- tituted with one or more halogen atoms; a phenyl group which is optionally subatituted with one or more BAD OHIGINAL ot ——

OC, [42 halogen atoms, Cin alkyl groupe, halogenated Cyn alkyl groups, Cig alkoxy groups, halogenated Cn alkoxy groups, Cy_4 alkylthio groups, halogenated Cyn alkylthic~ groups, nitro groups, cyano groups, or 3,4-methylenedioxy grours; a furyl group which is substituted with one or more Cyn alkyl groups; =a thienyl group which is optionally substituted with one or more halogen atoms or Ci-u alkyl groups; an =OpRn group, wherein ir represents a Ci-6 alkyl group, a Cog alkenyl group, a phenyl group which is optionally substituted with one or more halogen atoms, a benzyl group, a pyridyl group which is substituted with one or more halogenated Cy a alkyl groups, or an ~NRgRq g;roup, wherein Rg and Rg each represents a Cin alkyl ¢;roup, and n is O, 1, or 2; or a -CO(NH) _R, group, wherein R, pg represents a Cig alkyl group which is optionally substituted with one or more halogen atoms,

or a phenyl group which is optionally substituted with one or more halogen atoms; and m is O or 1; provided that compounds represented by the general formula (II1''): Biome, BAD ORIGINAL -169- er —

. BR RE t / ° NG

\ M.— TT Ry, I 3 wherein Ro and Ryo are simultaneously a hydrogen atom, n halogen atom, a cyano group, or a phenyl group which is optionally subatituted with the same Or different Cio alkoxy group or Zy _» alkylthio group at the para- position; and wherein one of Ra, an Ryo is 8 hydrogen atom and the other is 2 halogen atom, a methyl group, or a phenyl group, are excluded. -170-- BAD ORIGINAL —~ en —t