CA1115204A - 2-imino substituted isothioureidobenzene - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

2-Imino substituted isothioureidobenzene products useful as anthelmintics and fungicides are disclosed. The products may be prepared by several different methods includ-ing treating a 2-iminothioutridobenzene with a base and either an organic halide, a diester of sulfuric acid or a diester of sulfurous acid or treating a 2-aminoisothioureidobenzene with an appropriately substituted aldehyde.

Description

` ` ::

Field of the Invention This invention reIates to 2-imino substituted isothioureidobenzenes, to processes for making such compounds, to methods of treating helminth and fungus infections and to anthelmintic and antifungal compositions containing them.
Description of the Invention British Pat. Nos. 1,214,415 and 1,307~250; UOS~
Pat. Nos. 3,958,008; 3,860,586 and 3,836,569 and Netherlands Pat. No. 7,401,787 disclose numerous thioureas useful as anthelmintics, though none have a subs-tituent on the sulfur.
German Pat. No. 2,303,048 discloses 2-acylated amino-S-substituted isothioureidobenzenes as anthelmintics. How-ever, there are no references disclosing compounds having both an imino substitutent on the benzene ring and a substituted sulfur atom in the thioureido group. Other patents disclosing anthelmintic compounds include U.S.
~, Pat. Nos. 3,865,948 and 4,005,217; also, British Pat. No.
1j350,277.
An object of this invention is to provide a new class of 2-imino substituted isothioureidobenzenes (I, infra), methods for preparing these compounds, compositions containing said compounds and to their use as anthelmintic and antifungal agents.
The novel 2-imino substituted isothioureidobenzenes (I, infra) of this invention have the following structural ~ formula:

: : ,

- 2 - ~

" .

~ N=CHR I :~

11 1 :
NH-C=N-C-OR
SR

: wherein R is alkyl, for example, lower al}cyl of from 1- :
to 8 carbon atoms such as methyl, ethyl, n-propyl, _-butyl/ lso-butyl, sec-butyl, pentyl, hexyl, heptyl~ ::
octyl and the like; alkenyl, for example, lower alkenyl of from 3 to 8 carbon atoms such as propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl and the like;
alkynyl, for example, lower alkynyl of from 3 to 8 carbon atoms such as propynyl, butynyl/ pentynyl, hexynyl, heptynyl, octynyl and the like; polynuclear aralkyl such as naphthylmethyl, naphthylethyl, phenan~hrenylmethyl and .-the like; mononuclear aralkyl such as benzyl, phenethyl, phenylpropyl and the like which may be ring-substituted with from 1 to 3 groups such as halo, alkyl, alkoxy, :
nitro, cyano and the like; mononuclear aryloxy lower :
alkyl, for exa~ple, phenoxy lower alkyl of from 3 to 6 carbon atoms in the alkyl group including phenoxypropyl, phenoxybutyl, phenoxypentyl, phenoxyhexyl and the like;
~ cycloalkylalkyl/ for example, cycloalkyl lower alkyl of -~
: from 5 to 6 nuclear carbon atoms such as cyclopentylmethyl, cyclopentylethyl~ cyclohexylmethyl, cyclohexylethyl and the like; cyano lower alkyl of from 3 to 6 carbon atoms such as cyanopropyl, cyanobutyl, cyanopentyl, cyanohexyl ":
.

.

- 3 - . .
.,/`'~. ' :' ' and the like; hydroxy lower a~kyl of from 3 to 8 carbon atoms such as hydroxypropyl, hydroxybut~l, hydroxypentyl, :
hydroxyoct~l and the like; aralkenyl, for example, poly-and mononuclear aralkenyl such as phenylpropenyl and the like; alkoxyalkyl, for example, lower alkoxy lower alkyl, such as methoxypropyl, ethoxypropyl, methoxybutyl~ propoxy-butyl and the like; alkoxycarbonylalkyl, for example, lower alkoxycarbonyl lower alkyl wherein lower alkyl has 3 to 5 carbon atoms, such as methoxycarbonylpropyl, ethoxycarbonylbutyl, ethoxycarbonylpentyl, propoxycarbonyl-hexyl and the like; phthalimido lower alkyl such as phthalimidobutyl and the like or phenoxycarbonylalkyl, for example, phenoxycarbonyl lower alkyl o~ from 3 to 6 carbon atoms such as phenoxycarbonyl ~ropyl, phenoxycarbonyl butyl, phenoxycarbonylpentyl, phenoxycarbonylhexyl and the like; Rl is alkyl, for example, lower al~yl of from 1 to 6 carbon atoms such as methyl, ethyl~ n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, pentyl, hexyl and the like or lower ~lkoxyalkyl such as methoxyethyl ethoxyethyl, propoxyethyl and the like; R2 is alkyl, for example, lower alkyl of from 1 to 6 carbon atoms; substi-tuted or unsubstituted aryl~ of from 4 to 6 nuclear carbon ato~s, for example, mononuclear aryl of from 4 ko 6 nuclear carbon atoms, polynuclear aryl of from 10 to 14 car~on atoms, heteroaryl of from 5 to 6 nuclear atoms --containlng from 1 to 3 ~eteroatoms selected from oxygen, nitrogen or sul~ur, examples of aryl include phenyl, naphthyl, thienyl, pyrldyl, furyl, furylmethyl, pyrroli-dinyl~ pyrrolyl, isothiazolyl~ oxadiazolyl, thiadiazolyl, .

- 4 -, . . .

imidazolyl,isooxazolyl, N-methylpyrryl, oxazolyl, pyrimidyl, and the I ike which may be unsubstituted or substttuted with from I to 3 radicals selected from halo, such as chloro, bromo and the like, lower alkyl having from I to 5 carbon :

- 5 ~1 .
.

atoms, lower alkoxy having from 1 to 5 carbon atoms;
di-lower alkyla~ino such as dimethylamino and the ].ike, lower alk2noylamino ol from 1 to 5 carbon atoms; phenoxy, : ::
benzyloxy, 3,4-lower alkylenedioxyphenyl, phenylthio lower alkyl, cyano, nitro, alkylthio or ary:Lthio and the l~ke;
and X is hydrogen, nitro, halo, such as chlorc,iodo, bromo fluoro and the like; lower alkanoyl of from 2 to 5 carbon atoms, such as acetyl, propionyl, butyryl, pentanoyl and the like; lower alkyl of from 1 to 4 carbon atoms such ~:
as methyl, ethyl, propyl, _-butyl and the like; lower alkoxy, such as methoxy, ethoxy, propoxy, butoxy, pentoxy and the like; thiocyanato, a radical of the formula:
Y-S(O)~ wherein Y is lower alkyl of from 1 to 5 carbon atoms;.lower alkenyl (C3-C6)~ lower alkynyl (C3-C6), cyclo lower alk~l (C3-C7), a 5- or 6-membered heterocycle, such a pyridyl, thienyl, furyl, pyrimldyl, thiazolyl and the like or mononuclear aryl such as phenyl and n is an integer of O to 3, X is also lower alkylcarbonylamino, . .
such as methylcarbonylamino and the like, lowe~ (Cl-C4) 2~ alkoxy carbo~ylamino such as methoxycarbonyl isopropoxycarbonylamino and the like, a 5- or 6-membered cycloalkylcarbonylamino such as cyclopentylcarbonylamino, cyclohexylcarbonylamino and the like; a radical of the formula: Y~9- wherein Y' ~s mononuclear aryl such as phenyl and the like; cyclo lower alkyl (C3-C7), a 5- or

6-membered heterocycle, such as pyridyl, 2-thienyl, furyl and the like or X is also a radical of ~he formula: Y"O-wherein Y" is lower alkyl (Cl-C5)~ mononuclear aryl, such as phenyl and the like, lower alkenyl, mononuclear arylkyl or a 5- or 6-membered heterocycle and, when substituted, the substituents on .

~i , ;, the Y, Y' and Y" are selected from halo, cyano, lower alkyl, lower alkoxy, lower alkanoyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, phenyl~hio, phenylsulfinyl, phenylsulfonyl, phenoxy, halophenoxy, benzyloxy, trifluoromethyl or carbo lower alkoxy and.
the nontoxlc, pharmaceutically or agronomically acceptable acid addition salts such as those formed with acids such as hydrochloric, sulfuric, nitric, phosphoric, acetic, citric, benzoic, lactic and the like and amides of the ester such as amino, mono- and di-lower alkylamino and the like. Representative R2 radicals include chloro-phenyl, bromophenyl, methylphenyl, ethylphenyl, butylphenyl, pentylphenyl; 2,6-dichlorophenyl; 3,4-dichlorophenyl;
methoxyphenyl, ethoxyphenyl, dimethylaminophenyl, acetamido;
3,4-methylenedioxyphenyl, methylthiophenyl) phenylthio-phenyl and the liXe.
; When compounds of general Formula I can exist in various isomer and stereoisomer forms, all such isomers and their mixtures and racemates are included within the scope of the present invention.
Preferred Embodiment A preferred embodiment of this in~ention relates to the 2~imino substi~uted isothioureidobenzenes ~Ia, infra) of the following structural formula:
xl ~ - N=CHR5 \~NHC =NC-oR4 ` . ' .
sR3 ~;
a

7 :

~',': ' wherein R3 is lower alkyl, lower al]cenyl, lower alkynyl, benzyl, 2,6-dichlorobenzyl, phenethyl, cycloalkyl lower alkyl of from 5 to 6 nuclear atoms, phenoxy lower alkyl of from 3 to 6 carbon atoms, cyano lower alkyl of from 3 to 6 carbon atoms, lower alkoxy carbonyl lower alkyl wherein lower means from 3 to 6 carbon atoms, phthalimido : -lower alkyl, phenyl lower alkenyl of from 3 to 6 carbon : atoms or hydroxy lower alkyl; R4 is lower alkyl; R5 is .
mononuclear aryl of from 4 to 6 nuclear carbon atoms, poly-nuclear aryl of from 10 to 14 nuclear carbon atoms or. .. .... .
heteroaryl of from 5 to 6 nuclear atoms containing from 1 to 3 hetero atoms s~ch as _, _, or p-nitrophenyl, o, m or ~-dimethylaminophenyl, lower _, _ or ~-alkoxyphenyl, o, m or ~-cyanophenyl, _, m or p-acetamidophenyl, methylene-dioxyphenyl, phenyl, 2-furyl, 5-methyl-2-furyl, 2-thienyl, o, _, or p-halophenyl, lower o, m or Ip-alkyl phenyl or dihalophenyl and Xl is in the 4 or 5 position of the benzene ring and is selected from hydrogen, lower alkyl carbonylamino, lower alkoxycarbonylamino, lower alkoxy, lower alkanoyl, propylthio, propylsulfinyl, propylsulfonyl, propylsulfonyloxy, propoxysulfonyl, phenylthio, phenyl- ..
sulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy or benzoyl. Especially preferred are those compounds .. .. ::
wherein Xl is hydrogen, 4-benzoyl, 5-propylthio or . .... .... ... ::
5-phenylthio. These compounds exhibit particularly good .
anthelmintic and antifungal activity. ~ .
The present invention also provides a method of combatting or preventing fungal infections in plants subject .

- 8 - . .
~, . ';.
: . , , . . . ' ~ ' `

to such infections which comprises applying to such plants or to seeds thereof~ or to a locus in which said plants are growing, an effective amount o~ a compound of Formula I
or a compound o~ Formula Ia as defined hereinabove.
This invention further provides a method of controlling the growth of fungi in an environment or on a substrate which is subject to deterioration due to attack by said fungi, which comprises applying to said environment or to said substrate an effective amount of a compound of Formula I or of a compound of ~ormula Ia as defined herein- ``
abo~e. The invention further provides a composition useful as a seed protectant, soil fungicide or foliar fungicide which comprises from about 0.1 to about 200 oz. per 100 lbs.
o~ seed, from about 0.1 to about 50 lbs. per acre and from about 0.25 to about 10 lbs. per acre, respectively, of a compound of Formula I or of a compound of Formula Ia as defined hereinabove.
The products may be prepared by several alter- ;
native processes including treating a 2-imino substituted thioureidobenzene with a base and an organic halide, a diester of sulfuric acid or diester of sulfurous acid or by treating a 2-amino substituted isothioureidobenzene with an aldehyde.
The first method for preparing the 2-imino sub-stituted isothioureidobenzenes (I, supra) of this '`:
:
''' "` `

,,';i, .:, : , . ~ .. .. .

invention comprises treating the corresponding 2 imino substituted thioureidobenzene (II, infra) with a base, for example, an alkali metal or alkaline earth me~al base, such as sodium hydride, calcium hydride, sodium hydroxide, -potassium hydroxide, calcium hydroxide~ potassium carbonate and the like followed by treatment with either an organic halide, a diester OL sulfuric acid or diester of sulfurous acld. ~he reaction may be conducted at a temperature in the range of from -10C. to about 60C. for a period of time of from a few minutes to about 24 hours. Any solvent in which the reactants are reasonably soluble and sub-stantially inert may be employed. Suitable solvents include dimethylformamide, acetone, 1,2-dimethoxyethane, dimethyl sulfoxide and the like. ~he following equation illustrates thls process: :
X X

( ~ =CHR2 + ~ase R ~ ~ N=CHR2 H-C~HC-ORl or RS04R S
S R

II I
wherein R, Rl and X are as defined above and x2 is halo such as chloro, bromo or iodo.
A second method for preparing the compounds of Formula I comprises treating 2-amino substituted iso~ -; thioureidobenzene with an aldehyde (R2CH0) in a manner similar to that described below for the ,.
.

.

~ ~ ~ 5 2~ L~

preparation of the compounds of Formula III~ ~he following equation illustrates this process:

N~2 ~ I

NHC=NCOR
SR
IIa wherein R, Rl, R2 and X are as de~i~ed above. : ~ .
The compounds of Formula II are either known co~pounds or ma~ be prepared by treating an appropriately substituted l-imino-2-aminobenzene (III, ~:
infra) with a carboalkoxyisothiocyanate (IV, infra), to afford ~he desired compou~ls of Formula II. The ;;
lQ followlng equation illustrates this process:

X X . ' N=C~S2 + S=C-NC-ORl ~ ( ~ C 2 ~

2 ~CN~CORl . ~ . .
S . ~
III IV II
': ~'.' whe~ein Rl, R2 and X ara as defined above~ ~his .reaction ~ :
is conveniently conducted in a suitable inert solvent such as diethyl et~e~, acetone, and the lika for a period of time of from 30 minutes to 6 ~ours.

We have found that the compounds of Formllla II, supra, which have been disclosed as ~nthelmintics are also useful as f~ngicides.
Compound IIa is prepared by ~he reaction S O
of a thioureidobenzene (V~ infra) where Z-C-~C-ORl with RX2, RS03R or RSO~R under the same conditions as described in the preparation of Formula I from For~ula II.
The compownds of Formula II and also the compounds of Formula IIIa, l-substituted~imino-2-subs~ituted aminobenzene, may be prepared by treating thecorrespondingly substituted isothioureidobenzene or substituted 1,2-diaminobenzen~ (V, inPra), respectively, with an aldehyde~ The following equation illustrates this process: . :
~' ~ '"'' ''' .
X ~ ' ~ "''.', ~ 2 + R2cHo ~ ~=cH~2 NH-Z' NH ,,, V IIIa wherein R2 and X are as defined above and Z' is hydrogen or -C-NXC-OR
S .;.
wherein Rl is as defined abo~e. This reaction is 2 generally conducted at a temperatllre in the range of from about 0C. to about l1C. for a period of time of _ ~2 -from one minute to about 24 hours. Suitable solvents which can be employed include acetone, methanol~ ethanol, " ..*
iso-propanol, methylCellosolve,dimethyl~ormamide 9 di-methyl sulfoxide and the like. ~n acid catal~st such as p-toluene sul~onic acid, sulfuric acid and the like may be employed. Any water formed durin~ the reac~ion may be removed b~ azeotropic distillation.
When X is the radical YS, the sulfinyl (i.e.,Y-S0-) and the sul~onyl product can be prepared by treating said YS substituted co~pound with one or two equivalents of an oxidizing agent~ respectively. The oxidizing agent may be ~-chloroperbenzoic acid, perbenzoic acid, peracetic acid, sodium h~pochlorite and the likeO
The reaction is eonducted at a temperat-lre in the ranga of from -20C. to 50C. for a period of time of ~rom about 5 minutes to 24 hours. Any substantially inert solvent in which the reactants are reasonabl~ sol~ble may be employed including methylene dichlo~ide, chloroforms carbon tetrachloride, benzene,toluene~ chlorobenzene, acetone and the like.
The thioureidobenzene of Formula V
S O ~' ,'.
tZ'C-NHC-oRl) is prepared by treating a 1,2-diaminobenzene deri~ative or l-amin~-2 nitrobenzene derivative with a carboalkoxy isothiocyanate in the manner described abo~e and when a nitrobenzene reducing said nitro to an amino ~roup by reductio~ methods well-known to those skilled in the art.
' *Trademark. Methyl "Cellosolve;' is ethylene glycol monomethyl ether.
- 13 ~ - ~

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

~5;2~-~

2-Imino substituted isothioureidobenzenes o~ Formula I are anthelmintics and have broad spectrum activity against parasites of animals, especially warm ..
blooded anim~ls, including both matuxe and immature parasitic forms. In particular, these compounds exhibit high activity against va~ious helmintic infectio~ o~ the intestinal tract of economically important animals, coupled with low systemic toxicity to the host animal.
For example, the disclosed compounds are 10 generally effective in clearing mice of worm infections, ~ ~
for laboratory purposes, including: Syphacia abvelata and . .:
Asp1cularis tetraPtera' the migratory stages of Ascaris suum, ~menole~sis nana and Nemato,spiroides dubi~us.
Compounds of Formula I have been ~
15 demonstrated as e~ficacious against gast~ointestinal : :
parasites in sheep, such as Moniezia 5P~, ~aemonchus .:~
contortus, Osterta~ia ~, Trichost~on~lus s~P, Nemat?dirus sp~ EL L~ ovis, Cooperia ~, Capillaria ..
~, Stron,~,yloids papillosus, Bunostomum ~ a~ h~um and ...
O,es~ph,a~ostomum ~ The compounds are active agai~st lung worms in ruminants especially Dictyocaulus filaria, in sheep and DictYocaulus ~3~ and in cattleO The compounds tI) may also be use~ in treating Fasciola ~ L~a ln cattle. In addition, the compounds are 2~ e~fective against.llver flukes tFasciola hepatica) in : .
sheep and c~ttlel Animals of low weight are t~ea~ed with unit doses ranging no higher than a few milligr~ms;
whereas, animals of high bod~ wsight~ such as ruminants, ~ 14 -,: ,. .
"!'`;~ .,:
.. .
. . . . : .

require proportionately larger unit doses ranging up to several grams~ Preferably, a single dose is a~ministered for each a~imal species based on the weigh~ of that species~
~he amo~nt OL ingredient administered will depend on the weight of the host and will usually be a unit dosage between about 1 mg./kg. and 125 mg./kg.
of body weight. It is contemplated that dosage units containing the compounds of Formula I of ~his in~ention as the essential active ingredient w'll be administered, 10 oraliy or by injection~ in the treatment and control of helmintic infections ln man and domestic animals such as sheep, cattle, horses, dogs, cats t fish, swine and goats.
Further, applicants have found that the compounds of Formula I and Formula II of this invention 15 display broad spectrum antifungal activity. It is con- ~-templated, there~ore, that antifungal compositions con talning these compounds as an essential active ingredient will be employed in controlling th~ growth of fungi in or on animals and plants as well as in ~he paint, wood, 20 textile, cosmetic, leather, tobacco, fur, rope, paper, pulp, plastic, luel, rubber and food industries.
When used as an anthelmintic agen' for the treatment and/or prevention of helminthiasis, ~he ~ovel compounds of For~ula I of this invention may be 25 administered orally, rectally, intranasall~, su~inguall~
or topically, in a u~it dosage form such as a capsule, ..
bolus, tablet, suppository, paste, gel, spray, powder, ointment, cream or as a liquid drench. ~hey may also be administered orally by intimately dlspers~g th~m in ar ~ .
' ,.,..:: :"

":

animal feedstuff or by using them as a top dressing or in the form of pellets which are added to a ~inished feed. Alternatively, they may be admlnlstered to animals in a l~quid carrier vehicle by intraruminal, intramuscular and intratracheal injection. In addition, polymer~c im-plants providing a controlled release rate can be employed for administration. The quantity of active material re-qu~red to g~ve the best anthelmintic response will depend upon the particular compound employed, the species of animal to be treated and the type and severity of hel-minth infection. Good results are usually obtalned when there is administered a total dose of from about 5 to about 125 mg. of actlve lngredient per kg. of animal body welght. Such total dose may be given at one time or ~n divided doses over a short per~od of time such as 1 to 3 days.
The 2-imino substituted isothioureidobenzenes and acid addition salts and metal salt complexes of the present invention are useful as agricultural fungicides and can be applied to various loci such as the seed, the soil or the foliage. The compounds can be employed in technical or pure form or in solutions or in formulations.
The compounds are usually taken up in an agronomically acceptable carrier or are ~ormulated to render them suitable for use as fungicides. For ex~mple, the com-pounds can be formulated as wettable powders, emulsifiable concentrates, dusts, granular ~ormulations, aerosolsl or flowable emulsion concentrates. In such formulations, the compounds are usually extended with an agronomically . . . , , .~ ., . . . . : :

~$~

acceptable liquid or solid carrier and, when desired, suitable surfactants are also incorporated.
By the term "agronomically acceptable carrier" is meant any substance which can be utilized to dissolve, disperse, or diffuse the compounds without impairing the effectiveness of the compound and which is environ-mentally acceptable.
It is usually desirable, particularly in the case of foliar spray formulations, to include ad~uvants~ such as wetting agents, spreading agents, dispersing agents, stickers, adhesives and the like in accordance with the agricultural practices. Such ad~uvants commonly used in the art can be found in the John W. McCutcheon, Inc.
publication "Detergents and Emulsifiers, Annual."
In general, ~he compounds of this invention can be dissolved in organic solvents such as acetone, methanol, ethanol, dimethylformamide, pyridine, dimethyl sulfoxide and the llke and the re~ultlng solutions can be extended with water. The concen~rations of the solution can vary from about 1~ to about 90~ with a preferred range being from about 5% to about 50~.
: :, ~
For the preparatlon of emulsifiable concentrates, the compound can be dissolved in suitable organic solvents, or a mixture of sol~ents, toge~her with an emulsifying . .
agent which permits dispersion of the fungicide in water.
The concentration of the active ingredient in emulsifiable concentrates is usually from about lO~o to about 90% and in ;~
flowable emulsion concentrates, can be as high as about 75,0.
Wettable powders suitable for spraying, can be -,~. ;.~
~17 . ' :' prepared by admixlng the compounds with a finely divided solid, such as clays, inorganic silicates and carbonates, and silicas and incorporating wetting agents, sticking agents, and/or dispersing agents. The concentration of active ingredients in these formulations is usually in the range of from about 20% to about 98%, preferably Lrom about 40% to abou~ 75~. A typical wettable powder is made by blending 50 parts of l-iminot2-furylmethyl)-2-(3-carbomethoxy-s-butyliso~hioureido)benzene~ 45 parts of a synthetic preclpita~ed hydrated silicon dioxide sold under the trademark Hi-Sil ~3, and 5 parts of sodium lignosulfonate. In another preparatlon a kaolin type (Barden) clay is used ln place of the Hi-Sil wettable powder, and in another preparation 25% of the Hi-Sil is replaced with a synthetic sodium sil~co aluminate sold under the trademark Zeolex ~ 7.
Dusts are prepared by mixing the compounds with "
~inely divided iner~ organic or inorganic solids.
; Materials useful for this purpose include botanical flours, silicas, silicates, carbonates and clays. One convenient method of preparing a dust is to dilute a wettable powder with a finely divided carrier. Dust concentrates containing from about 20~ to about 8~% of the active ingredient are commonly made and are subsequently dlluted to from about 1% to about l0~ use concentration.
The compounds o~ this in~ention can be applied as --~
funglcidal sprays by methods commonly employed, such as conventlonal highDgallonage hydraulic sprays, low-gallonage sprays, air-blast sprays, aerial sprays and , '... ':

''.

dusts. The dilution and rate of application will depend upon the type of equipment employed, the method of appli-cation and diseases to be controlled, but the preferred ef~ective amount is usually ~rom about 0.1 lb. to about 50 lbs. per acre of the active ingredLent.
As a seed protectant, the amount of ~ungicide coated on the seed is usually at a dosage rate o~ ~rom about O.i to about 20 ounces per hundred pounds of seed.
As a soil fungicide the compound can be incorporated ln the soil or applied to the surface usually at a rate of from about 0.1 to about 50 lbs. per acre. As a foliar fungicide, the compound ls usually applied to growing plants at a rate of from about 0.25 to about lO lbs. per acre.
Fungicides which can be combined with the fungicides of this invention lnclude:
(a) dithiocarbamates and derivatives such as:
ferrlc dlmethyldlthiocarbamate (ferbam), z$nc dimethyldithiocarbamate (ziram), manganese ethylenebisdithiocarbamate (maneb) and its coordination product with zinc ion (mancozeb), zinc ethylenebisdithiocarbamate -(zineb), zinc propylenebisdith~ocarbamate (propineb), sodium methyldithiocarbamate (metham), tetramethylthiuram disulfide (thiram), the complex of zineb and polyethylene thiuram disulfide, 3,5-dimethyl-1,3,5-2H-tetra-hydrothiadiazine-2-thione (dazomet~ 7 and mix-tures of these and mixtures wlth copper salts;
. ; .

~'' .
~, j~l , , ,:
.
:. ~ . : .. : .. ..

(b) nitrophenol derivat~ves such as:
dinitro~ methylheptyl)phenyl crotonate (dinocap), 2 sec-butyl-4,6-dinitrophenyl-3,3 dimethylacrylate (~inapacryl), and 2-sec-butyl-4,6-dinitrophenylisopropyl carbonate;
(c) Heterocyclic compounds such as N-trlchloro-methylthiotetrahydropntha:Limide (captan)~ N-trichloromethylthiophthalimide (folpet), 2-: heptadecyl 2-imidazole acetate (glyodine) , 2-10 octylisothiazol-3-one, 2,4-dichloro-6-(o-chloro-anllino)-s-triazine, diethyl phthalimidophosphoro-thioate, 4-butyl-1,2,4-triazole,5-amino-1-[bis-(dimethylamino)-phosphinyl]-3-phenyl-192,4-triazole, 5-ethoxy-3-trichloromethyl-1,2,4~
thiadiazole~ 2,3-dicyano-1,4-dithiaanthraquinone (dithianon), 2-thio-1,3-dithio-~4~5-b] quin-oxaline (thioquinox), methyl l-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl 9 2-(4'-thiazolyl)benzimidazole (thiabendazole), 4-(2-chlorophenylhydrazone)-3-methyl-5-isoxa-zolone, pyrldine~2-thio-1-oxide, 8-hydroxy-: quinoline sulfate and metal salts thereof; 2,3-dihydro-5-carboxanilido-6-methyl-1,4 xathiin-:4~4-dioxide-2,3 dihydro-5-carboxanil~-do-6- d methyl-1,4~oxathiin,~-(phenyl)-~-(2,4-dlchloro-: phenyl)-5 pyrimidinyl-methanol (triarimol), cis-N-~(1,1,2,2-tetrachloroethyl) thio]-4-cyclohexene-1,2-dicarboxyimide, 3-[2-(3,5-dimethyl-2 oxycyclohexyl-2-hydroxy~]-glutarlmide ~:

-20 ~

2~4 (cycloheximide), dehydroacetic acid, N~
2,2-tetrachloroethylthio)-3a,4,7,7a-tetra-hydrophthalimide (captafol), 5-butyl-2-ethyl-. ` amino-4-hydroxy-6-methylpyrimidine(ethirimol), : 5 acetate of 4-cyclododecyl-2,6-dimethylmorpholine (dodemorph), and 6-methyl 2-oxo-1,3-dithiolo- -[4g5-b]quinoxaline (quinomethionate).
(d) miscellaneous halogenated fungicides such as tetrachloro-p~-benzoauinone (chloranil), 2,3- :
dichloro-1,4-naphthoquinone (dichlone), 2,3- ::
dichloro-2,5-dimethoxybenzene (chloroneb), 3,5,6-trichloro-o-anisic acid (tricc~mba), 2,4,5,6-te~rachloro~sophthalo nitrile (TCPN), 2,6-dichloro-4-nitroaniline (dichloran), 2- .
chloro-l nitropropane, polychloronitrobenzenes ; such as: pentachloronit~obenzene (PCNB) and tetrafluorodichloroacetone; ~ -(e) ~un~icidal antibiotics such as:
griseofulvin, kasugamycin and streptomycin;
(f) copper~based fungicides such as: :
cuprous oxide, baslc cupric chloride, basic ` . -copper carbonateg copper naphthena~e and : ~ Bordeaux mixture; and ~g) miscellaneous fungicides such as: :
~5 diphenyl, dodecylguanidine acetate (dodine) 3 '~
phenylmercuric acetate~ N-eth~lmercurl-1,2,3g6-tetrahydro 3,6-endomethano-3,4,5,6,7,7-hexa- :
chlorophthalimide, phenylmercuric monoethanol ammonium lactate, ~dimethylaminobenzenediazo -- 21.o ~' `'.

sodium sulfonate, methyl isothiocyanate, 1-thiocyano-2,4-dinltrobenzene~ l-phenylthio-semicarbazide, nickel-containing compounds, calcium cyanamide, lime sulfur, sulfur, and 1,2-bis(3-methoxycarbonyl~2-thioureido) benzene (thiophenatemethyl).
The compounds of this invention can be advantageously employed in various ways. Since these compounds possess broad spectrum fungicidal activity, they can be employed in the storage o~ cereal grain. These complexes can also be employed as fungicides in turf, frult orchards, vegetables and golf course applications. Other applications o~ the compounds of this invention will suggest themselves to those skllled in the art of agriculture and horticulture.
The following examples illustrate the compounds o~
this invention and the methods by which they may be prepared. -However, the examples are illustrative only and it will be apparent to those having ordinary skill in the art that all of the products embraced by Formula I, supra, may also -~
be prepared in an analogous manner by substituting the appropriate starting materials for those set forth in the examples.
,:

i :
..

~ . .
- 22 ~
. ~ .

EX~MP~E 1 - 3-Iminophenylmethyl-h-(3-carbomet'noxy-S-Ste~ A - ~-Im~r.o~hen~ n~l-4-aminobenzo~henone To a solution of 3,~-diaminobenzophenone ', (4.213 gO; 0.02 mole) in methanol (50 ml.) cooled to 0C. is added benzaldehyde (2012 g.; 0.02 mole~. The solution is stirred at 0C. for one hourO The precipitate is collected '~
by filtration and dried to yield 3.0 g. of 3-iminophenlJl- '~
methyl-4-aminobenzophenone 7 m.p. 112-116C. ~, Elemental analysis ~or C20~l6N2o - ,~, , Calc.: C, 79.97; H, 5.37; N, 9.33 ~ound: C, 80.11; H, 5.57; N, 9.28 ,' -' Ste~,B - 3-Iminophenylmethyl-~-(3-carbometh~xy "' thioureido),benzo~h To a solution of 3-iminophenylmethyl- , ~-aminobenzophenone (0.5 gA; 0~00166 mole) in diethylether '- , (100 ml.) is added carbomethoxy isothiocyanate (0.19 g.;
0.00166 mole). ~he solution is stirred at room temperature ~ ', ~or three hours. The precipitate is collected by filtration and dried to yield 0.35 g. of 3-iminophenylmethyl-l~-(3 '~
carbomethox~thioureido)benzophenone, m~p. 19~-195~C. (dec.). ' , Elemental analysis for C23~19N303S ' , Calc.: C 7 66.17; H, 4.59; N, 10.07 -~ Found: C, 65~81; H~ 4.53; N, 9.80 Ste~ C - 3-Iminophenylmethyl-~-(3-carbomethoxy-~o a solution of 3-iminop~enylmethyl-~-t3-carbomethoxythioureido)benzophenone (1.1 g.; 0~0026 mole~ in dimethylformamide (1OOO ml.) is added water ~3 ml.). Additional dimethylformamide (25~0 ~1.) is . .- . . , . . . . . ,: . .

added to dissolve some precip-ltate and then sodium hydroxide (50% aqueous; 0.21 g.; 0.0026 mole) is added. The resulting solution is stirred at room temperature for 1-1/2 hours and then methyl iodide (0.~8 gO; 0.0026 mo~e) is added. The solution is stirred for one hour at room temperature and then poured into water (250 ml.). ~he precipitate is collected by filtration and dried to afford 0.95 g. of 3-iminophenylmethyl-4-(3-carbome~hoxy-S--methylisothioureidc) benzophenone, m7p. 140-142C. (dec.).
Elemental analysis for C24H21N303S
; Calc.: C, 66.80; H, 4.91; N, 9.74 Found: C, 65068; H, 4.86; N, 10.44 ..

E~AMP~E 2 - 3-Iminophenylmethyl-4-(3-carbomethox~-S-meth~
isothioureido)benzo~henone To a suspension of 3-iminophenylmethyl-4-(3-carbomQtho~ythioureido)benzophenone (2.09 g.; 0.00~ ~ole) in a mixture of acetone (20 ml.) a~d water (3.0 ml.~ is added aqueous sodium hydroxide solution (50%; 0.4 g.). The mixture is stirred for one ho~lr at room temperature. To the solution is added methyl iodide (0.71 g.; 0.005 mole). Withi~
two minutes a thick suspension forms. Additional acetQne ~20 ml.) and water (3.0 ml.) is added and stirring is con~inu~d for 18 hours. The preclpitate is collected by filtration and dried to a~ford 2.05 g. of 3-imin~phenylmethyl-~-(3-carbometho~y-S-methylisothioureido)benzopheno~e, mOpO
157-158C. (dec.).
Elemental analysi 24 21 3 3 Calc~: C, 66.80; ~, 4~91; N, 9.74 Found: C, 66.31; ~, 4.83; ~, 9.95 -- z4 .
', .':

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

EXAMPLE ~ - 2-Imino(2,5-dichloro)phenylmethyl-~-(3-carbo-methoxy-S-methylisothioureldo)benzo~heno~ne Step A - 2-Imino-(2,6-dichloro~phenylmethyl-~-~r~ D .eA~re To an ice cooled solution of 3,~-diaminobenzophenone (8.48 g.; 0.0~ mole) in methanol (100 ml.) is adaed a solution of 2,6-dichlorobenzaldehyde (7.o6 g.; 0.0~ mole) in methanol (100 ml.). The solution is stirred at 0C. for one hour and at room temperature over the week-end. The precipitate formed is collected by ~iltration and dried to afford 1105 g. of 2-imino-(2,6 dicnloro)phenylmethyl-~-aminobenzophenone, m.p. 1l~1-144C.
Steo B - 3-I~ino~2,~-dichloro)phenylmethyl-4-~ carbemethox~hioureido~b~nzophenone To a solution of 2-imino-(2,6-dichloro)-phen~Jlmethyl-4-aminobenzophenone (2.08 g.; 0.005 mole) in i diethyl ether (600 ml.) is added carbomethoxy isothiocyanate (0.88 g.; 0.0075 mole). The solution is stlrred at room tsmpera~ure ~or 18 hours~ The precipitate which ~orms is collected and dried to yield 1.8 g. of 3-imino(2,6-dichloro) phenylmethyl-~-(3-carbomethoxythioureid~)benzophenone, m.p.
197C. (dec~).
El~,mental analysis for C23El7Cl2N33S ; : .
C~lc.: C, 56.79; H, 3.52; N, 8.64 Fou~ C, 57.~9; H, 3.66; N, 8.84 ~ - 3-Iminophenylmeth~1-4-(3-c~rbomethoxy-S-~=~ .
~o a solutlon of 3-imino(2,6-dichloro)-phen~lmethyl-~-(3-carbomethoxythioureido)benzophen~le (2.43 g.~ 0~005 m~le) in dimethy~ormamide (100 ml.~ is added water (5.0 ml.) a~d then sodium ~droxide (50~ aqueous;
00~ g~; 0.005 mole). The solution ls stirred for 1-1/2 hours .. .
: - .
:
~l -25 5 2! ~

and then methyl iodide (0071 g~; 0.005 mole) is added.
The solution is s~irred for one-hal~ hour. The pracipitate which forms is collected by filt~ation and dried to a~ford 1.3 g. of 3-iminophe~ylmethyl-4-(3-carbomethoxy-5 S-meth-~lisothioureido)benzophsnone, m~p. 63-68C~ ~dec.).
Elemental analysis ~or C24E19C12N3~3S
Calc.: C, 57.60; H, 3.83; N, 8.~0; S, 6.41 Found: C, 56.65; H, 3.8C N, 8.48; S, 5.8 EXAMP~E 4 - 3-Imino-t~-methylphenyl)methyl-4-(3-carbo-mer~hox~-S-me~h~lisothioureido~benzophenone Ste~ A - 3-Imino-(4-methylphenyl)methyl-~
aminobenzophe~n~ne To an ice cooled solution of 3,4-diaminobenzophenone t6.36; 0.03 mole) in methanol t75 ml.) is added ~-tolualdehyde t3.6 gO; 0.03 mole).
The solution is stirred at 559 for one hour and at room temperature for 18 hours. A precipitate is collected by filtration and dried to afford 4.5 g. of 3-imino~
methyl)phenylmsthyl-~-aminobenzophenone~ mOp. 136-137C.
SteP B - 3-Imino-(4-methylphenyl)methyl-4-(~-carbomethoxythioureido~ben~enona To a solution of 3-imino-(4-methyl-phenyl)m~thyl-~-aminobenzophenone (4.5 g~; 0.01~5 mole) in dimethoxyethane ~75 ml.) and diethyl ether ~25 ml.) is added carbomethoxy isothi~yanate (1.68 g.j 0.01~5 ~ole). The solution is stirred at room temperature~or 10 mlnutes ~t w~ich time a precipitate begins to form.
Stirring is continued at room temperature for cne hour and ths precipitate is collectsd by filtra~ion and dried to afford 3.9 g. Or 3-imino~ methylphenyl)methyl-4-(3-carbometho~ythioureido)benzophenone, m~p~ 201~-202C. ~`
(dec~

~ 26 -Elemental analysis for C24H21N303S
Calc.: C, 66.80; H, 4.91; N, 9.74 ~ound: C, 66.73; H, ~.79, N, 10.18 Ste~p C - 3-Imino-(4-methylphenyl)methyl-4-- (3-carbomethoxy-S-methylisothio-~L~b~O~ ~ -~ .
To a solution of 3-imino-(~-methyl-phenyl)methyl-4-(3-ca~bomethoxythioureido)benzophenone (2.0 g.; 0.00463 mole) in dimethylformamide (100 mlO) an~ ~;
water (5 ml.) is added sodium hydroxide (50~ aqueous; 0.37 g.). The solution is stirred at room temperature for one hour at which time methyl iodide (0.66 g.; 0.00463 mole) is added. The solution is stirred at room temperature for 20 minutes and then poured into water (1.0 1.). A
precipitate forms and is collected by filtration and dried to afford 2.1 g. of 3-imino~ methylphenyl~meth~Jl-~ (3-carbo~ethoxy-S-methylisothioureido)ben20phenone, m.p.
40-45C. (dec.).
~lemental ~alysis for C25H23N303S
Calc.: C, 67.39; H, 5.20; N, 9.~3; S, 7.20 Found: C, 66.81; H, 5.22; N, 9.9~; S, 7.23 EXAMPLE ~ - 3-Imino-(4-chlorophenyl)meth~ (3-carbo-methoxY-s-meth-ylisothloureido2~ben~ aa~
~ Ste~ A - 3-Imi~o (4-c;qlorophenyl)methyl-~- -; ~ 25 To an ice cooled solution of 3,4-diaminobe~zophenone (8.4 g.; 0.0~ mole) in methanol (100 ~ ml.) is adde~ -chlorobenzaldehyde (5.6 g~; 0Oo4 mol0).
;~ The solution is stirred at 0 ' 5~C7 for one hour and at room temperature for 18 hours. The precipitate which ~i~ formis is collected and dried to afford 9.2 g. o~ 3-imino-(L~-chlorophenyl)methyl-~-aminobenzophenone~ m.pO 123-125C.

-t,~

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

Elemental analysis for C2 ~ 15ClN20 CalcO: C, 71.7~; H, ~.52; H, 8.37 Found: C, 7.87; ~ 3; N, 8.60 ~ 3-Imino-(4-chlorophenyl)methyl-~-To a solution of 3~imino-(4-chloro)~
phenylmethyl-~ aminobenzophenone (7~9 a .; 0.02 mole) in diethyl ether (700 ml.) is added carbomethoxy isothio-cyanate (2.3~ g.; 0~02 mole). The solution is stirred at room temperature for 18 hours. The precipita~e whicn forms is collected by filtration and dried to afford 606 g. of 3-imino-(~-chloro)phenylm~thyl-4-(3 carbomethoxythioureido)-benzophenone, m.p. 212-216C. (dec.).
Elemental analysis for C23ElgClN303S
Calc.: C, 61~12; H~ 4.01; N, 9.30 Found: C, 61~37; H, ~.0~; N, 9.72 p ~ - 3-Imino-(4-chlorophenyl)methyl-4-~3-carbomethoxy-S-methylisothio-ureido)benzo~henone _ _ To a solution of 3-imino-(~-chloro-phenyl)methyl-~-(3-c~rbomethoxythioureido)benzophenone (~.52 g; 0.01 mole) in dimethylformamide (200 ml.) and water (5.0 ml.) is added aqueous sodium hydroxide ~0%
aqueous; o.8 g. ). The solu~ion is stirred at room temperature for one hour and then methyl iodide (1.~2 g.;
0.01 mole) is added. ~he solution is stirred at room temperature for 25 min~tes and then poured into water (700 ml.). The suspension which forms is then stirred for 5 minutes and the precipitate is collected by ~iltratio~ and dried to afford ~.3 g. of 3-imino~
chlorophenyl)methyl~ 3-carb~metho~y-S-methylisothio-ur~ido)benzophenone, m~p. 156~-157C~ (dec.)~

C: r .

Elemental analysis for C2~H20ClN303S
Calc.: C, 61.86; H, 4.33; N, 9.02 Found: C, 60.97; ~, ~o21; N, 9.51 EXAMPL5 6 - 3-1minophenylmethyl-~!-t3-carbomethoxy-S-~ ~ ~
To a solution of 3-imincphenylme~hyl-4~
carbomethoxythioureido)benzcphenone (2.35 g.; 0.0054 mole) in dimethylformamide (100 ml.) and water (10 ml~) there is added aqueous sodium hydroxide solution (50%; 0.4~ g.).
The solution is stirred at room temperatu~ for one hour and then benz~l bromide (0.93 g.; 0.005~ mole) is added.
The solution is stirred at room temperature for 15 minutes . . .
and is then poured into 500 ml~ of water. The suspension which forms is stirred at room temperature for 5 minutes and then collected by filtration and dried to a~ford ~ 2.~5 g. of 3-iminophenylmethyl-~-(3-carbomethoxy-S-; benzylisothioureido~benzophenone, m.p. 50-70C. (dec.).
E~emental anal~s for C30E25N343S
Calc.: C, 70.98; H, 4.96; N, 8.28 Folmd: C, 69.~4; H, 4.98; N, 8.90 , . , EXAMPLE 7 - 3-Iminophenylmethyl-4-(3-carbomethoxy-S-. .
To a suspension of 3-iminophenylmethyl~
(3-carbomethoxythioureido)benzophenone (2.09 ~O; 0.005 mole) ~n acetone (~0 ml.) and water (6.0 ml.) is added an aqueous sodium hydroxide solution (50% aqueous; 0.~ g.)~ ~' The~suspe~sion is stirred at room temperature for one hour a~d then allyl bromide (0.6 g.; 0.005 mole) is added and ~he solution is stixred a~ room temperature over the week-end. The precipitate which ~orms is collected by filtration '; ~,.
~ 29 ~
f~

and then dried to afford 1.3 g. of 3-iminophenylmethyl)-4-(3-carbomethoxy-S-allylisothioureido)benzophenonel m.p. 125-127C.
Elemental analysis for C26H23N3O3S
Calc.: C, 68.25; H, 5.07; N, 9.:L8 Found: C, 67.93; II, 4.98; N, 8.79 EXAMPLE 8 - 1-(3-Carbomethoxy-S-methylisothiouredio)-2-aminophenylmethyl-5-propylthiobenzene Step A - 1-(3-Carbomethoxythioureido)-2-nitro-5-propylthiobenzene To a stirred mixture of 2-nitro-5-propanylthioaniline (21.2 g.; 0.10 mole) in acetonitrile ; (50 ml.) is added portionwise carbomethoxy isothiocyanate (11.7 g.; 0.10 mole). The reaction mixture is maintained at room temperature and is filtered ko remove a small amount of dark colored insoluble material. The clear filtrate was ; permitted to stand at room temperature for two hours and the precipitate which forms is collected by filtration, washed with cold acetonitrile and dried to yield l-(3-carbomethoxy-thioureido)-2~nitro-5-propylthiobenzene (17.9 g.), m.p.
122-125C.

_tep B - 1-(3-Carbomethoxythioureido)-2-amino-5-propylthiobenzene A mixture of 1-(3-carbomethoxythioureido)-2-nitro-5-propylthiobenzene (4.4 g.; O.Q134 mole), stannous chloride (15.2 g.; 0.067 mole), concentrated hydrochloric acid (25 ml.), methanol (50 ml.) and acetic acid (50 ml.) is stirred and refluxed for one half hour. The reaction mixture is poured into ice water and basified with 50% aqueous sodium hydroxide solution. This solution is extracted with dichloro-methane and the dichloromethane removed to afford 3.8 g. of 1-(3-carbomethoxythioureido)-2-amino-5-propylthiobenzene. -:
. "` ' Step C - 1-(3-Carbomethoxythioureido)-2-- iminophenylmethyl-5-pyropylthio-benzene To an ice-cooled solution of 1-(3-carbomethoxythiouredio)-2 amino-5-propylthiobenzene (1.0 g.;
0.00334 mole) in methanol (100 ml.) is added benzaldehyde (0.35 g.; 0.00334 mole). The solution is stirred at 5C
for an hour and the precipitate which forms is collected by filtration and dried to afford 0.6 g. of 1-(3-carbomethoxy-thioureido)-2-iminophenylmethyl-5-propylthiobenzene, m.p.
109-110C. `~
Elemental analysis for ClgH21N3O2S2 Ca~c.: C, 58.89; H, 5.46; N, 10.84 Found: C, 58.85; H, 5.46; N, 11.02 Step D - 1-(3-Carbomethoxy-S-methylisothioureido)-2-iminophenylmethyl-5-propylthiobenzene To a solution of 1-(3-carbomethoxythio-ureido)-2-iminophenylmethyl-5-propylthiobenzene (0.5 g.;
0.00129`mole) in acetone (20 ml.) and water (3.0 ml.) is added an aqueous sodium hydroxide solution (50~; 0.103 g.).
The solution is stirred at room temperature for 1~1/2 hours and then methyl iodide (0.183 g.; 0.00129 mole) is added.
The reaction mixture is stirred at room temperature for one hour and then poured in water tlO0 ml.). The suspension formed is stirred at room temperature for 1-1/2 hours and then the precipitate collected by filtration and dried to afford 0.35 g. of 1-(3-carbomethoxy S-methylisothioureido)-2-iminophenylmethyl-5-propylthiobenzene, m.p. 80-83C.
(dec.).
Elemental analysis for C20H23N3O3S
Calc.: C, 59.82; H, 5.77; N, 10.46; S, 15.97 Found: C, 59.73; H, 5.88; N, 10.36; S, 15.89 .:
':

3~ (3-Carbomethoxy-~-methylisothioureido)-2-esulfon~lbenzene Ste~ A - 2-Iminophenylmeth,yl-4-benzenesulfonyl-To an ice-cooled solution of 2-amin~
benzenesulfonyl~niline (5.2 g.; 00021 mole) in methanol (25 ml.) is added benzaldehyde (2.23 g.; 0.021 mole). The solu-tion is stirred at 0C. for 1-l/2 heurs. A suspension ~orms which is stirred at room temperatllre overnight and ~hen the precipitate collected by fil~ration is washed with methanol and then ether and then ~ried to afford 6.0 g. o~ 2-iminophenylmethyl-4-benzenesulfonylaniline, m.p. 159-160C.
Elemental analysis for C19H16N202S
CalcO: c~ 67.83; H, 4.79; N, 8.33 Fo~lnd: C, 67.54; H, 4.90; N, 8.62 S,e~ 3 ~ 3-Ca~bomQthoxythioureido)-2-imino-To a solution of 2-iminophenylmet'nyl-4-benzenesulfon-~laniline (4.5 g.; 0.0134 mole) in acetone (250 ml.) is added carbomethoxy isothiocyanate (lo 57 g~;
0.0134 mole). ~he solution is stirred at room temperat~re ~or two hours and the precipitate which forms is collected by filtration, washed with ether and dri'ed to afford 2.15 ,~
gr of l-(3 carbometho~thioureido)-2-iminophenylmethyl-~
2~ benzenesulfonylbenzene, m.p. 207-208C. (dec.). ',' Elemental analysis for C22Xl9N3hS2 Calc.: C~ 58.26; H, 4.22; N, 9~27 ,'' ~ ' Found: Cs 58.32; E, 4.14; ~, 9O40 ~,.' ~-' ~'`' ' '''~

, ~ ' ~ 32 - , ~

(3-Carbomethoxy-S-met~ylisothioureido)-2-iminophen-Jlmethyl~ benzenesl;Llfonyl-benzene To a suspension of 1-(3-carbomethoxy~
thioureido)-2-imin~phenylmethyl-~-benzenesulfonylbenzene (1.0 g.; 0.0022 mole) in acetone (10 ml.) an~ water ~1.0 ml.) ; there is added an aqueous sodium h-~droxide solu~ion (50%;
0.18 g~). This mixture is stirred at room te~perat~re for 2 hours and a fine suspension which for~s is removed by filtration. To the filtrate is added methyl iodide (0.~13 g.; 0.0322 mole). The solution is stirred at room temperature , for 8 days. The reaction mixture is filtered and to the filtrate is added water ~300 ml.) and ,the resulting mixture is stirred at room temperature for 3 hours. The precipitate which forms is collected by filtration and dried to afford' 0.3 g. of 1-~3-carbsmethoxy-S-m3thylisothioureido)-2~imino-phen~Jlmethyl-4 benzen~sulfonylbenzene.
Elemental analysis for C23H21N30~2 Calc.: C, 59.08; H, 4.53; N, 8.99 Found: C, 58067; H, 4.39; N, 8.79 "

EXAMPLE 10 - 3-Imlnophen~ et'nyl-4-(3-carbomethoxy-S-bltyl-,isoth,ioureido)benzophenone~ _ _ .. ~ . .
To a suspension of 3-iminophenylmethyl-~
(3-carbomethoxythioureido)benzophenone (3.12 g.; 0.0075 mol ,25 in acetone (60 ml~) an~ water (10 ml.~ there is added an aqueolls sol~tion of sodium hydroxide (50~; 0.6 g.). The mixture is stirred at roo~ temperature for 1-1/4 hours and to the solution form there is added n-butyl iodide (1038 g.3 0O007~ mole). The solution is stirred at room temperature 3 for 2 hours and the suspension which forms is collected by filtration, washed with ether and dried to afford 1.9 g.

'..':

, ~ 3 - , ~$~

o~ 3-iminophenylmethyl-~-(3-carbomethcxy-S-n-butylisothio-ureido)benzophenone, m.p~ 105~-107C, (dec.).
Elemental analysis for C27~27N303S
Calc.: C, 68.47; H, 5.75; N, 8.87 Found: C, 67.56; ~, 5~77; N, 8.52 EXAMPLE 11 - 3-Iminophenylmethyl-4-~3-carbomethoxy-S-(2,6-dichlorophen ~ )isothioureido~ben20~henon~
To a suspension of 3-iminophenylmethyl-4-(3-carbometho~thioureido)benzophenone (3.12 g.; 0.0075 mole) in acetone (60 mlO) and water (10 mln ) i~ added an aqueous solution of sodium hydroxide (50%; 0.6 g.). The mixture is stirred at room temperature for 2 hours and then ~-bromo-2,6-dichlorotoluene (1.3 g.; 0.0075 mole) is added. This solution is stlrred at room temperaturefor one half hourO The precipitate which forms is collected by filtration, washed with ether and dried to afford 2.5 ~;
g. of 3-iminophenylmethyl-4-[3-carbomethoxy-S-(2,6-di-chlorophenyl)isothioureido]benzophenone, m.p~ 148-150C~
(dec~).
Elemental analysis for C30H23C12N3~3S
Calc~: C, 62.50; X, 4.02; N, 7.29 Found: C, 61~6~ , 3.95; N, 7.21 EXAMPLE 12 - 3-(Imino-(4-nitrophsnyl)methyl-~-(3-carbo~

~ 3-Imino-(4-nitrophenyl)methyl-~-~o a solution of 3,4-diaminobenzo-phenone (8.48 g.; 0.04 mole) in methanol (100 ml.) is - ;
added p-nitrobenzaldehyde (6.04 g.; 0.0~ mole). The re-actlon mixture is stirred for 5 days and the precipitate - is collected by filtration and dried to afforcl 12.h5 g.
of 3-imino-(4 nitrophenyl~methyl-~-aminobenzophenone, m.p. 161~-163C. (dec.~

SteP B - 3-Imino-(~-nitrophenylmethyl)-~-(3-To a solution o~ 3-imino-(4-nitro-phenylmethyl-~ aminobenzonhenone (6.9 g.; 0.02 mole) in acetone (225 ml.) there is added carbomethoxy isothio-cyanate (2~34 g.; 0~02 mole)0 ~he solution is stixred at room temperature for 18 hours. The pxecipitats which forms is collected by filtration and then dried to afford 7.35 g. of 3-imino-~4 nitrophanylmethyl) 4-(3 carbomethoxythioureido)benzophenone, ~.p. 229-230Co (dec.).
- 3-Imino-(4-nitrophenyl)methyl-4-(3-carbomethoxy-S-methylisothio-ureido)benz_phenone_ _ To a suspension of 3 ~mino-(4-nitro-phenylmethyl)-~ (3 car~omethoxythioureido)benzophenone (~o62 g~; 0~01 mo~e~ in acetone (I60 ml.) and water (2~ - -ml~)there is added an aqueous solution of sodium hydroxide (50~; 0.8 g.)0 ~he so~ution is s~irred at room temperature for one hour at which time me~hyl iodide (1.42 g.; 3.01 mole) is added. The suspension forms and th2 re~ction mlxture is stirred for 30 minutes. The precipitate is collected b~J filtration, washed with ether and dried to afford 2.55 g. of 3-imino-~4-nitrophenyl)methyl-4-(3-carbomethox~-S-methylisothioureido)benzophenone, m.p.
. .
;~ 180-182C. ~dec~) T~ . ' : , , .
ElementaI analysis for C2 ~ 20N405S
Calc.: C, 60~49; H, 4,23; N, 11~76 Found: C, 60090; ~, 4.33; N, 1108'7 ' , ':

~ ~ 35~

EXAMPLE 1~ - 3~Imino-(2-na~hthylmethy~ ~ (3-carbometho~y-S-methy,lisothioureido~benz~
Step A - 3 Imino-(2-napht~llmethyl )-~-amino-benæoPhenona , __ To an ice cooled solution of 3~-diaminobenzophenone (10.6 g.; 0.05 mole) in methanol (120 ml.) is added 2-naph~hylme~hyl (7.8 g.; 0.05 mole).
The solution is stirred at 5C. for 2 hours at room temperature overnight. Sul~uric acid (5 arops ) is added 10 and the solution stirred an additional 5 days at room tem~
perature. The precipitate is collected by filtration and dried to afford 5.25 g~ of 3-imino-(4-nitrophen~l)methyl-4-aminobsnzophenone, m.p. 141-143C. (dec.). ~, Elemsntal analysis for C24X18N20 ,~
Calc.: C, 82.26; H~ 5.18; N, 8.00 `~, Found: C, 81053; ~, 4.98; N, 7019 St~ B - 3-Imino-(2-na~hthyl me~hyl)-4-(3- `
carbo ethox~t ioureido~benzo~ aL~ ;' To a solution of 3-imino-(2-naph~hyl)- ''' 20 ~-(aminobenzophenone) (4.0 g.; 0.0114 mole) in acetone (50 ml.) is addsd carbomethoxy isothiocyanate (1.34 g.; 0.0114 mole)~ A suspension foxms within 5 minutes and stirring ~`
; is cont~nued at room temperature for 18 ~ours. Ths pre-cipitate is collected by filtration, washed successively ~ ' 25 with acetone and ether and then dried to afford 3.1 g. of 3-imino-(2_naphthylmethyl )-4-(3-caxbomethoxythi~ureido) benzophenone, m.p. 207-209C. (dec.).
El~menta~ analysis ~or C27H21M303S ', Calc~: C, 69~36; X~ 4~53; N, 8.99 30 Found: C, 69.37; ~ 4.58; N, 8.83 ' ' .' :`,'' ., .

~p C - 3-Imino-(2-naphthyLm2~yl )-~-~3~
carbometho~y-~-msthylisotnioureido) be~30~henone ,_ To a suspension of 3-imin~-(2-naphthyl-methyl)-~-(3-carbomethoxythioureido)benzophenone (2.5 g~;
0.0535 mole) in acetone (25 ml.) and ~ater ~3 ml.) thexe is added an aqueous sodium hydroxide solution (50%; 0.43 g.). -The mixture is stirred at room temperature for 18 hours an,l then filtered. To the filtrate is added methyl iodide (0.76 g.; 0.00535 mole). Tne precipitate ~orms within 5 ~inutes. ~he suspension is stirred at room temperature for 30 minutes and the precipitate is collected by filtration, -, washed with sther and dried to afford o.8 g. of 3-imino-(2_naphthylmethyl)_4-(3_carbomethoxy-S-methylisothioureido)-benzophenone, m~p. 147-149.5C. ~dec.).
Elemental analysis for C28~23N33S
Calc.: C, 69.83; ~, 4.81; N, 8.73 Found: C, 69.28; H, ~.82; N, 8.50 ''' EX~MPLE 14 - 3-Imino~ methoxyphenylmethyl~ 4-t3 carbo-methoxy-S-methylisothioureido)benzophenone Ste~ A - 3-Imino-(~-methoxyphenylmethyl~
a ,inobenzoPhenone ~; '' To an ice-cooled solution o~ 3,4-~ diaminobenzophenone (10.6 g.; 0.05 mole) in metha~ol (120 ml.) i 25 is added ~ anisaldehyde (6~8 g.; 0O05 mole). The solution is stirred at 5~C. ~or 2 hours an~ at room tempera~ure for 18 hours. S~llfuric acid (5 drops) is added to the solution and it ls stirred an additlonal 9 days at room tempera~ure. ,~
~ Th~ precipitate is collected by filtration, washed with ethe~
'f 30 and then dried to af~ord ~.2 gO of 3-amino-(4~methoxyphen~Jl- -methy~-~ amlnobenzophenone, mOp. 129-131C. (decO).

.~` ,.

.

St~ 3-Imino-(4-methoxyphen~lmethyl)-4-(~-carbomethoxvthioureido~benzo~heno-Qe To a soluti~n of 3-imino-(4-me~ho~y-phen~lmetnyl)-~-aminobenzophenone (4029 g.; 0.0127 mole) in acetone (75 ml.) is added carbome~hoxy isothiocyanate ~1049 g.; 0.027 mole). The solution is s~irred at room temperature for 18 hours ~a precipitate forms withi~ 3 minutes). ~he precipitate is collected by filtration, washed with ether and then dried to afford 3.3 g~ OL : ~ .
3-im m o-(4-methoxyphenylmethyl)-4-(3-carbomethoxythio-ureido)benzophenone, m.p. 182-184C. (dec~). ;
Step C - 3-Imino-(4-meth~phenylmethyl) 4-t3-carbo~ethoxy-S-methylisothioureido)-benzo~henene ~o a suspens~on of 3-imino-(4-methoxy-p~enylmethyl)~ 3-carbomet~oxythioureido)benzophenone (2.5 g.; o.oos6 mole) in acetone (20 ml.) and water (4 ml.) there is added a~ aqueous solution ~f sodium hydroxide (50%; 0~45 g.). Th~ reaction mixture is stirred at room temperatu~e for two hou:~s. A solid which forms is removed by filtra-tion and to the clear filtrate is added methyl iodide ~0.79 g.; 0.0056 mole). A precipikate forms with~n 5 mi~utes. The suspension is stirred at room temperature ~or 30 minutes and the precipitate is collected by filtra tion, washed with ether and dried to affQrd l.l g. of 3-imino~ -methoxyphen~Jlmethyl)-4-(3-carbomet~oxy-S-met~ylisothioureido~benzQphenone, m.p. 136-138C. (dec.), Elemental analysis for C25H23N3~S
Calc.: C, 65006; H, 5.02; N, 9.10 Found~ G, 64.87~ H, 500~; N, ô.87 - 3~~

.. .

EXAMPLE 1~ - 3-Imino~2-nitrophenylmethyl~-4-(3-carbo-m SteP A - 3-Imino-~2-nitrophenylmethyl)-~-aminobenzophenone ~o an ice-cooled solution of 3,4-diaminobenzophenone (8.~8 g.; 0.0~ mole) in methanol (100 mlO ) there is added o-nitrobenzaldehyde (6.0~ g.;
0.04 mole). ~he mixture is stirred at 5C~ for one hour and at room temperature for 18 hours. Sulfuric acid ~3 drops) is added to the solution and then within one hour a suspension forms. The suspension is stirred at room temperature ~or 18 hours and a precipitate collected b~
~iltration, washed with ether and dried to afford 10,85 g.
of 3-imino-(2 nitrophenylmethyl)-~ aminobenzophenone, m.p. 140-142C. (dec.). This material is used in the next step without furtner purification.
Ste~ B - 3 Imino-~2-ni~roph~nylmethyl)-4-(3-ca ~ enzo~ eno~e To a solution of 3 imino-(2-nitro-phenylmethyl)-4-aminobenzophenone tlOnO g~; 0.029 mole) in acetone (100 ml.) is added carbomethoxy isothiocyanate (3.~ g.; 0.029 mole). The solution is stirred at room temperature for 3 hours and the precipitate collected by filtration and dried to afford 7.3 g. of 3-imino-(2-nitro-phenylmeth~ -(3-carbomethoxythioureido)benzophen~ne, m.p. 215~-217C. (dec.).
Ele ental analysis for C23HlgN40sS
; Calc.: C, 59O73; H, 3.92; N, 12.12 ~ound: C, 59.65; H, 3.98; N, 12~28 ~.
~ - 33 -.. . .. . . .

St~p C - 3-Imino-~2-nitrophenylmethyl)-4-~3-carbomethoxy-S-methylisothioureido)-To a suspension of 3-imino-~2-~itro-phanylmethyl)-4-(3-carbomethoxythioureido~benzophen~ne (4.62 g.; 0.01 mole) in acetone (160 ml.) and water (24 ml~) is a~ded an a~ueous solution of sodillm hydroxide (50~;
0.8 g.). ~he mixture is stirred at room tempera~ure for one hour an~ a fine precipitate which forms is removed b~ filtration~ To the filtrate is added methyl iodide 42 g.; 0.01 mole) and the solution stirred at room ~ ;
temperature for 45 minutes~ The precipitate which forms is collected b-J filtration and dried to afford 2.65 g. -of 3-imino-~2-nitrophenylmethyl~ 3-carbometh~xy-S-methylisothioureido)benzophenone, m.p. 167-168.5QC. (dec.).
Elemental analysls for C24H20N405S
, Galc f 5, 60~49; H, 4.23; N, 11.76 ; Found: C, 60.55; H, 4.20; N, 11O65 EXAMPLE 16 - 3-Imino-(3,4-dichl~rophenylmeth~ -(3-ca~bometho~- _ meth~L___hiour~ d? lbenz ~henone 1:
Ste~ A - 3-Imino-~3,~-dichlorophenylmet~yl)-~-aminobenzo~henone __ , _ _ __ To a solution of 3,4-diami~obsnzo-phenone (6.15 g.; 0.029 mole) in methanol ~100 ml.~, cooled to 5~C., is added 3,4-dichlorobenzaldehyde (5.08 g.;
0.029 mole). The mixture is stirred at 5Co for one hour and at room temperature for 18 hoursO The precipitate which forms is collected by filtration and dried to af~ord 7.96 g. of 3-imino-(3,4-dichlorophenylmethyl)-4-amino be~zophe~ne, mOp. 147-148C.

.: ' - 40 ~
, ...

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

Elemental analys s for C20~l4cl2N2o Calc.: C, 65.05; H, 3.82; N, 7~59 Found; C, 6L.60; H7 3.79; ~, 7.49 Ste~ B - ~-Imino-(3,~-dichlorophenylmethyl)-4-~ o~o~}~sLiD=oureissi~ æ- nonQ
To a solution o~ 3-imino-(3,4-dichlorophenylmeth~ -aminobenzophenone (7.0 g.; 0.019 mole) in acetone t200 ml.) there is added carbomethoxy isothiocyanate (2.22 g.; 0.019 mole). A preclpi~ate ~ormq within ~i~e minutes. The ~ixture is stirred at room temperature for 1-1/2 hours and the precipitate which forms is collected b~J filtration, washed with acetone and then ether and then dried to afford 6.9 g. of 3-imino-(3,4-dichlorophenylmethyl) ~-(3-carbometho~ythioureido)benzo-phenone, m.p. 214-126C. (dec.)~
Elemental an~lysis ~or C23~17cl2N30 Calc.: ~, 56.79; X, 3052; N, 8.64 Found: C, 56.76; H, 3.53; N, 8.43 3-Imino-(3,~-dichlorophenylmethyl)~
t3-carbometh~xy-S-methylisothioureido)-To a solution of 3-imino-(3,4-dichloro-phenylmethyl~-4-(3-carbomethoxythioureido)be~zophenone ~3O0 g.; 000062 mole~ in dimethylformamide ~225 ml.) and 25~ water (lO mlO) ~here is added an aqueous sodium hylroxide ~` ; solutiQn ~5C~o; 0~49 g . ) ~ The solution is stirred at room t~mperature for one hour and then methyl iodide (0.88 g.;
0.0062 mole) is add~d. The solution is stirred at room temperature ~or 20 minut~s and then poured into water tl~O lo ) ~ ~he susp~nsion is filtsred to collect the precipitate a~ then dried to afford 2.55 g~ of 3-imino-~3,~-dichlorophenylmethyl)-~-(3 carbomethoxy-S-meth~liso~
thioureido)be~zophenone, ~.p~ 168~-174C. tdec.).
41 ~
'..;.
.. . . .... ... . .. . .

Elemental analysis for C24H19C12N303S
Calc.: C, 57.60; H, 3.83; N, 8.40 Found: Cl 57.22; ~, 3.7~; N, 8.24 E~u~PLE 1~ - 3 Imino-(2-chlorophenylmethyl)-4-(3-carbo-methox~-S-methylisothioureido~benzo~henone Ste~ A - 3-Imino-(2-chlo~o~hen-Jlmethyl)-~-c~enzo~henone To an ice-cooled solution of 3,4-diaminobenzophenone tl6.96 g.; 0.08 mole) in methanol (200 ml.) is added o-chlorobenzaldshyde (11.2 g.; o.o8 ~ole). ~he solution is stirred at room tempera~ure ~or 30 minutes and the precipitate which separate~ is collected by filtration and dried to afford 20.5 g. of 3-imino (2-chlorophenylmethyl)-~-aminobenzoph~none, m.p~
112C. (dec.)~
3-Imino-(2-chlorophenylmethyl)-4-To a solution of 3-imino-(2-chloro-phenyl~ethyl)-~-aminobenzophenona (11.85 g.; 0.03 mole~ in acetone (100 ml.) is added carbomethoxy isothiocyanate (3.51 g.; 0.03 mole). It is necessary to add another portion of acetone (100 ml.) to the thick suspension which forms. ~he reaction mixture is stirred for an additional 30 minutes and the precipitate collected by filtration and dried to afford 9~0 g. of 3-imino-(2-chlorophenylmethyl)~
(~-carbomethoxythioureido)benzophen3ne, m~p. 20~-205~C~
(dec.).
Elemental analysi5 for C23H18C1~33S
Calc.: C, 61.12; H, 4.01; ~, 9.3 Found: C, 60.93; H, 4~00; N, 9.19 -'~

.
~ ''".
~ 42 ~
.

. .

3-Imino-(2-chlorophenylmethyl)-~-(3-carbomethox~-S-methylisothio-ureido~oe-~zo~h_none ~ _ To asuspension of 3-imino-~2-chloro-phenylmeth~l)-4-(3-carbomethoxythioureido~benzophenone ~3~0 g.; 0.0066 mole) in ace~one ~50 ml.) and water (10 ml.) is added an aqueous solution of sodium hydroxide (50%; 0.53 g.). The mixture is stirred at ro~m temperature for one nour and then methyl iodide (0.94 g.; 0.0366 mole~
is added~ ~he solution is st-rrsd at room temperature over the w-ek~end and the precipitate ~hich ~orms is collected by filtratio~ a~d dried to afford 0.9 g. of 3- ~-imino-(2-chlorophenylmethyl)~ carbomethoxy-S-methyl-isothioureido~benzophenone, ~.p. 140-142C. (dec.)~
Elemental analysis ~or ~24E20ClN303S
CalcO Cq 61086; H, 4O33; N, 9.02 ~ound: C, 61.7O; Ht 4.~0; ~, 8080 E~UL~PLE 18 - 3-I~ino-(4-dimethylaminophenylmeth~1)-4-(3-Ste~ A - 3 Imino-(4-dimethylaminophenylmethyl)-4-amin~ zo~henone _ _ To ~n ice-cooled solution of 3,~-diaminobenzophenone t8.48 g.; 0~0~ mole) in methanol (100 ml.) is added ~-N,N-dimethylaminobe~zaldehyde (6.0 g.; 0.0 mole~. The mixture is stirred at 5~C. for ons hour and at ~oom temper2ture for 18 ho~rsO Sulfuric acid (3 drops) is added to the reaction mixture and wit~in o~e hour a thick suspension forms. ~he reactio~ mixture is stirred at room temperature for an additional 8 hours and the precipita e 3o is collected and drled to afford 10~2 g. of 3-imino-(4-dimethylaminophanylmethyl)-~-aminobenzophenone, m.p.
171-173~C. ~dec~).

Y~ !
.
.

~5~

Elemental analysis ~or C22H21N30 Calc.: C, 76.94; H, 6.16; N~ 12.24 Found: C, 76.C8; ~, 6.17; N, 12~03 Ste~ B - 3-Imino-(4-dimethylaminophenylmethyl)-~-(3-carbomethoxythioureido)benzo-To a solution of' 3-imino-(4-dimethyl-aminophenyl~ethyl)-4-aminobenzophenone (9.6 g.; 0.0262 mole) in acet~ne ~2 1.) there is added carbomathox~ isothiocyanate (3~0 g~; 00 0262 mole). The solution is stirred at room temperature for 10 days and the acetone removed uncler vacuum. ~he residue is slurried in 100 mlO of acetone and filtered and washed with ether and then dried to a~ford 8~0 g. of 3-imino-t4-dimethylaminophenylmethyl)-~-(3-carbomethox~thioureido)benzophenone, m.p. 199C. (dec.) Elemental analysis for C25H2~N403S
Calc.: C, 65.20; H, 5.25; N, 12.17 ' Found: C, 65~05; H, 5.25; N, 11.98 `
Ste~ C - 3-Imino-(4-dimethylaminophenylmethyl)-4-(3-carbomethoxy-S-methylisothio-u ido)benz~hen~ .
~o a suspension of 3 imIno-(4-dimethyl-aminophenylmethyl)-4-(3-carbomethox~thioureido)benzophenone (3.0 g.; 0.0065 mole~ i~ acetone (50 ml.) and water (10 ml.) there is added an aqueous solu~ion of sodium hydroxide t50%; 0.52 g.). The mixture is stirred at room temperature i for one hour and then methyl iodide (0O93 gO~ is addedO ~he solution is stirred at room temperature for one hour ta precipitate begins to form after 15 mi~utes). The pre-cipitate which forms is collected by ~lltratio~ and dried to a~ford 0.6 g. of 3-imino-(4-dimethylaminophen~Jlmethyl~-~(3-carbomethoxy-S-meth~lisothioureido)benzophenone, m.p. 143-14~C. ~decO).

~ !
' Elemental analysis for C22H2lN30 Calc.: C, 76.9~; H, 501c); N, 12.2 Fou~l: C, 76.08; H, 6.17; Ng 12.03 ~ L~ Imino~ chlorophenyl)methyl-2-(3-carbo-metho~y-S-methylisothio~reido)-4-propylthio-benzena ~
Step A - l-Imino-(~-chlorophenyl)methyl-2-` (3-carbomet~oxythioureido)-4-propyl-; thiobenzene ~ _ 'O ~o an ice-cooled solution o~
amino-2-(3-carbomethoxythioureido)-~-propylthiobenzene (3.0 ~.) in absolute methanol tlOO ml.) there is added finely divided P-chlorobenzaldehyde (1.~ g.~. ~he yellow solution formed is stirred at 5C~ for one hour (precipitate forms after 10 minute~). The precipitate is collected by filtration. The yellow solid is dried to afford 1.2 g. o~ 1-imino-(p-chloroph~nyl)methyl-2-~3-carbometho~thioureido)-4-propylthiobenzene, m.p. 170~-172C. (dec.)O
Elemental analysis for Cl9H20ClN302S2 Calc.: C, s4-08; H, 4.78; N, 9.96 Found: C, 54.0~; H, 4.80; N, 9~89 Ste~ B - l-Im~no-(~-chlorophenyl)methyl-2~
carbomethoxy-S-methylisothioureido~-To a suspension o~ l-imino-~p-chlorophenyl~methyl-2-~3-carbomethoxyisothioureido~
propylthiobenzene (1.2 g.~ in acetone (30 ml~) and wate~
(10 ml.) is added sodiu~ hydroxide (0.23 g.; 50~ aqueous ~. ~
The mixture is stirred at room temperature for one hour and ~ ;
to the solution formed there is added methyl iodide (0.4 g.).
A precipitate forms immediately and the suspension is .: ,, , stirred at room temperature for 30 mi~utss. ~he p~ecipitate is collected by filtration, washed with ether and dried to a~ford 1.05 g. of 1-imino-(~-chlorophenyl)methyl-2 (3-carbomethoxy-S-methylisothioureido)-4-propylthiobenzene, m.p. 139 140C~
Elemental analysis for c2o~22clN3 2 2 Calc~: C, 55.09; H, 5.09; N, 9.64 Found: C, ~4.28; Hg 5.06; N, 9.29 EXAMP_E 20 - 1-Imlno-(2-thienyl)methyl-2-(3-carbomethoxy-~p_~ - l-Imino-(2-thienyl)methyl-2-(3-carbomethoxythioureido)-4 thiobenzene _ To an ice-cooled solution of 1-amino-2-(3-carbomethoxythioureido)-4-propylthiobenzen~
(3.0 g.) in methanol (75 ml.) there is added 2-thio-phenecarboxaldehyde ~1.12 g.). ~he solution immediately changes to a yellow color and within 15 mi,~utes a precipitate forms. ~he suspension is stirred at 5C. ;~
for one hour and at room temperature for 24 hours. The solid is collected by filtration and dried to afford 1.05 g. of l-imino-(2-thienyl)methyl-2-(3-carb~methoxy-~-methylisothioureido)-~-propylthiobenzene, m.p. 123-12~C.
Elemental analysis for C17H19N302S3 Calc.: C, 51~88; E, 4.87; N, 10.68 Found: C~ 51.52; H, ~.92; N, 10.63 '`'~.;~'j .-', .. ..

S~e~_B - l-Imino-(2-thie~yl)~ethyl-2-(3-carbomethoxy-S-methylisothioureido~-~-ProPYlthiobenzene To a mixture of l-imino-(2-thienyl)-methyl-2-(3-carbomethoxythioureido)-~--propylthiobenzene (1.0 g.) in acetone (20 ml.) and water (7 ml.), there is added a 50~ aqueous sodium hydroxide solution (0.203 g.~
The mixture is stirred at room temperature for one hour. ;-A solution forms after 15 minutes and to it is added methyl iodide (0.36 g.). The solution is stirred at room temperature for two hours and the precipitate formed is collected by filtration an~1 dried to afford 0.55 g. of l-imino-(2-thieny~)methyl-2-(3-carbomethoxy-S-methyliso-thioureido~-4-propylthiobenzene, m.p. 95C. (dec.~.
EXAMPLE 21 - 1-Imino-(P-chlorophenyl)methyl-2-t3-carbo-methoxy-S-methylisothioureido~-~ phenyl- ;
thiobenzene ~ _ _ _ ._ Stq~ A - l-Imino-(~-chlorophenyl~methyl-2-~3-carbometh~xythioureido)-~- `
phen~lth_obenzene _ _ ~o an ice-cooled solution of l-amino-2-(3-carbomethoxythioureido) 4-phenylthiobenz~n~ ~3.33 g.) ~:.
: in anhydrous methanol (300 ml.) is added finely powdered 2~ ~-chlorobenzaldehyde (1.~ g.). The solution is stirred at 5C. ~or one hour (a precipitate begins to form af~er 15 m~nutes). The solid formed is collected by filtrati~n ~ -and dried to afford 2.6 g. of l-imino-(~-chlorophenyl~
: methyl-2-(3-carbomethoxythioureido~-4-phenylthiobenzene, ~::
: ~: 3o m-p- 170 -172 C- ~:
~ l-Imino-(p-chloroph~nyl)methyl-2- -. : ::
: (3-carbomethoxy-S-methylisothio- ~:
u~
~: To a suspension of l-imino~
chlorQphenyl)methyl-2-(3-carbomethoxythioureido)-~

-phe~ylthiobenæene (1.6 go;~00351 mole) in acetone (30 ml.) and water (10 ml.) is added sodium hydroxide ~50~ aqueous;
0.28 g.)~ The mixture is stirred at room temperature for one hour and to the solution formed there is added methyl iodide (0.5 g.). A precipitate forms wi~hin five minutes and the suspension is stirred at room tempera~ure for 30 minutes. The precipitate is collectsd and dried to ~ford 1.02 g. of 1-imin~-(P-chloropheny1)methyl-2-(3-carbometh~xy-S-methylisothioureido)-~-phenylthiobenzene, m.p. 135-136C.
Elemental analysis fo~ C23x2oclN3o2s2 Calc.: C, 58.77; H, 4.29; N, 8.94 Found: C, 57.90; H, ~.20; N, 8.77 EXAMPLE 22 - 3-Imino-(2 thienyl)methyl-~-(3-carb~methoxy-S-meth~rlisothioureido)4enzo~henone _ A mixture of 3-imino-(2-thienyl~methyl-4-(3-carbomethoxythioureido)benzophenone (1.0 g.; 00 0624 mole) in acetone (12 ml.) and water (4 ml.) containing aqueous sodium hydroxide (0.22 g.; 0.0023 mole; 50%) is stirred at room tempera'ure for one hour and methyl iodide (0.l~ g.) is added. A precipitate forms almost immediately, filtered and the solid washed with water and dried to afford 0.7 g.
of 3-imino-(2-thienyl)methyl-4-(3-carbometh~xy-S-methyliso~
thioureido)benzopheno~e, m.pO 168-170C. (dec.~; 67% yield.
EXAMPLE 2~ - 1-Iminophenylmethyl-2-(3-carbomethoxy-S~allyl-To a suspension of l-iminophenylmethyl-2 (3-c~rbomethoxythiourei~o)-~-propylthiobenzsne (1.0 g.) in acetone (30 ml.) and water (10 ml.) there is added aqueous sodium hydroxide ~0.21 g.). The mix~ure is stirred at room temperature for one hour (a solution forms 20 minutes a~er the addition of sodium hydroxide3 and to it there i~ added ~ 48 -.

allyl bromide (0~36 g.). The solution is stirred at room temperature for two hours and is then poured into water (300 ~1.). The mixture is s~irred at room temperature for 24 hours and is vacuum filtered. The tacky yellow solid is stixred in hexane (50 ml.) and is filtered to yield 0.35 g. of 1-iminohe~ylmethyl-2-(3-carbomethoxy-S-isothioureido)-4 propyl~hiobenzene, mOp. 70-72C, In a manner similar to that described in the written exam~les, all of the 2-imino substituted thio-ureidobenzenes (I) of this invention may be p~epared bybeginning with an appropriately substituted l,2 diamino-bonzene co~pound and following substantially the procedures described herein. The following eauation iIlustrates the various reactions which ~ay be employed and taken together wi~h Table I, infra, depic~ the starting materials, inter-media~es and final products obtained.

~::
. . .
' . .

~ 49~

~,' "', x :

~2 NE~2 O / Va \
S=C-~CORl / \ R2ClIO , IV / \ .
1~ ~ ''.
X

2 ~--CTs ~R2 ~ICNlICO Rl NH2 Il 2 Sas~ \ R2CRO ~ S~C=NCO:3 ~)- R-Halo \ ~
., RS03R \~ X , ,, RS04R h~ =C~s~R

.~ ~ . \=~ 1 ,' N~ICNE~CO R
~ 2 :: I~ S
. (~)-Bas~ :
. ~ R-Xal RSO 3R ~ ~
~: : . or : ~ -: RSO, R ;::
. ~ ~ ~ , \ /

X ~ :

: ~ ~2 R2C~O ~ ~ ~=c~2 NC02R Cl ~NC02R

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

TABLE I
.

Ex. R Rl R2 X

2L~ -C2~I5 -C~3 ~ C~

- -C3H7 -C2H~ Cl 26 -CL~9 ~n~C3H7 27 -C5Hll -iso-C3H7 _~Br ;~

3r 28 -C6Hl3 -n-C4H

29 -C7~I15 -iso-CL~I9 Br~

-G8~17 -tert-C~H9 ~C 3 31 _~c:~2~2c~}~cN2 9~ 5 9 ~ 3 "

32 -(CN2~3CN=C~2 ~Z~-C6 33 -{CN2)~CN=CN2 -CN~

3~ ~cH2~ 5cH=c~2 -C~3 ~C2N5 "

-~C~I2)6CE2CX2 -CX3 ~\ '~

;' '"

51 - . .
~rl : ~

~.

Ex. R Rl R2 X

36 -CH2C--C-~I -CH3 ~) (5)-C4 37 -(Cx2)2c~cE -CE3 ~3 8 38 -(C~2)3C CE -CH3 ,~3 ~5)-CC~[3 . .

.
O , 39 -(CX2)4CaC:EI -CH3 _@3 (5) C~2~5 0~
L~ o - (CH2 ) 5C -CH -C~I3 ~ (5 ) -CC3X7 . O ,'.'': :.
~, - (CH2)6C-CE -CH3 ~I CC E ~`

42 C~I2~) -C~i5 ~ N2 ~5 3 ~3 C~2CX2~ C2H5 ~ )-OC2X5 f=~ . ' ~ ~ 44 -C~2~ -C-~302N~ (4 ) -~3E7 ~. .

~ . .
-CH2~ -C3~7~WO~ (lt)-OCL~H9 :;

6 ~CHZCH24~3 -CX3~CN (l~OC5H9 7 C~2~E2C~2~ -t_rt-C4~9~ ~ 5~-SC~J
.
.," f. -- 52 --~) ~X- R Rl R2 X
No O

48 ~ ~ Cl -~-C~H9 ~ OCH3 (5) -So4~) Ll 9 -CX2~c 3 -CH ~ ( 5) -S2 -Cx~cx2~oc~3 -CH3 ~ (4)-51 _(CH2)3-0~) -CH3 _~ (5)-0-S0 ~2 - ( C~2 ) L~.-O ~ -CH3 ~ ) -SCX3 53 - (C~2~ 5-4~) cYclo-C5H~ ~F (4) -SC3~7 54 -~CX2)6-o~3 cycl~2-C5E9 ~3 3 3 7 -C.'~2~ -n-C H ~~3~ F (5)-~02CH3 ;; 56 -(C~2)2~ -n-C3:~I7 -n-C3:E[7 ~ (5)-S2c3 7 I ' 11 ~ ~
t~ ~ 57 -CH2-0 -C~3 ~n~CL~ 9 (~) -NXCCH3 , 58 ~ (C~2) 2~ -C2H5 -a-C5Hll 5 ~ ~;;

C.~ 2) 3CN -CE3 - --C5dll ' .. . ,., ..-.

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

Ex. Rl R2 X

-(C~2)4C~ -C~3 --~ Cl (lt3-N-~c-oc2H5 61 -(CE2)5C~ -CH3 ~) ~ 5~ ilC-0-C~/ 3 62 - (CH2) 6CN 3 ( 4 ~ -NHC-OC4H9 o 63 - (C~I2 ) 30H " ( 5 ) -C~) :;

6~ -(CH2)L,.OH " C~3 ( ) ~) :.

r (CE2) 50X ti ~~ (5 66 ~(c~2)80~ (5)~S02-67 -CE-CHC~2~ " " (5)-C~Cl 68 ( 2)3 3 (5)_C4~30C~3 O
69 -~GH2)30C2H5 ,~ (5) _c~C~3 -(CH2)40C~3 -C~3 (5~-C

71 -(C~2)40C3 7 3 7 (5~-C-~)-CF3 72 -(C~2)3C-0C~3 -C2}~s " (5) C-~

_ 54 -- .

No R Rl R2 X

73 _(C~I2~4COC2x5 -C2Xs ~ 1 7L~ -(C~2)5C()c2 5 (~-SO{3CN

7 5 - ( CE2 3 6 C-OC3~7 - C3E7 " C4~so ~cc~3 76 - (CH2)~ C~3 " (~-~S02~CN

77 -(CE2)3C-o~3 " " (4~ s02~-CC~3 78 -(C~2)4C-0~) ~ S43CN ~
,, . :
3 :`
79 -(CE2) 5C-o4~) `

~ 1 ~0 -(CH2)6c-o4~ ~ ~t ( ~)-C4H9-a ~ ~
81 -C4Hg "

; ~ 82 -C3H7 -C2H5 ~;~ t 4 ) _C~

84 ~ C~3 -C4E~9 ~,N

. .
-C4~9 -C3H7 l!~S,II n ~1 ~ 55 ~ .

Ex.
No. R _ Rl R2 X
86 -C3H7 C2H5 ~ (5) -C--C2Hs -CH3 ~ / N H

88 -CH3 -CH3 ~ H

89 -C4H9 -C2H5 ~

.NCH3 9Q -C4Hg n-C4H9 ~ H
O' ~ ' ,, 91 -c3~7 tert-C4Hg~ N(5)-C3H~ ;

9~. -CH3 tert-C4H9~ ~(4)-C4H9 . 93 -C4Hg tert-C4H5 ~(4)-C2H5 : N

~: ' ' " ' , ~; ~ . :''' -:

: ~ ` 56 -EXAMPLE_94 - 1-Imino(2-furylmethyl) 2-(3 carbomethoxy-S-benzylisothioureide)benzene To 100.0 g (0.33 mole) of imino(2-furylmethyl)-2-(3-carbomethoxyth~oureido) benzene and 50.0 g. (0.395 mole) of benzyl chloride in 275 ml. of dimethyl sulroxide is slowly added 15.0 g (0.375 mole) of sodium hydroxide in 260 g. of water. The resulting mixture is stirred for 1/2 hour and the yellow precipitate is separated by filtration and recrystallized from 800 ml of methyle~e chloride-hexane (1:1) to give 91.1 g (70.1%) of l--imino-(2-furylmethyl)-2-(3-carbomethoxy-S-benzylisothioureido)- -~
benzene m.p. 112-114C.
Elemental Analysis for C21HlgNOS:
Calc: C,64.10; H~4.87; N,10.68; 0,12.20; S,8.15 Found: C,64.22; H,4.83; N,ll.ll; 0,12.29; S,8.24 EXAMPLE 95 - 1-Imino)2-furylmethyl)-2~ carbomethoxy-S-lS butylisothioureido)benzene To 5.0 g (0.0165 mole) of 1-lmino(2-~urylmethyl)-2-(3-carbomethoxythioureido)benzene and 3.6 g (0.01975 mole) of iodobutane in 80 ml. of N,N-dimethylformamide is added 0.7 ~ (0.0175 mole) of sodium hydroxide in 20 ml of water.
The resulting mixture is stirred for 1/2 hour and the yellow precipitate that formed is separated by filtration, washed with 50 ml of water and dried to give 3.4 g of crude product, m.p. 86-7C~ Recrystalllzation ~rom ether-he~ane affords 1-imino(2-furylmethyl) 2-~3-carbo-methoxy-S-butylisothioureido)benzene m.p. 84-85C.
Elemental Analysis for C18H21N303S:
Calc.: C,60015; H,5.89; N,11.69; 0,13.35; S,8.92 Found: C,59098; H,5.93; N,11.77; 0,13.83; S,8.90 ' . ' .

~7 ~
. . . ,, ., . . - .

EXAMPLE 96 - l-Imino(2 furylmethyl~2-(3-carbomethoxy-S-methylisothioureido)benzene A mixture of 3.03 g (.01 mole) l-imino(2-furyl-methyl)-2-(3-carbomethoxythioureido)ben~ene, 1.38 æ (-0 mole) of potassium carbonate, and 1.42 g ~.01 mole) o~
methyl iodide in 50 ml of acetone is re~luxe~ and stirred for l hour. The suspension is allowed to stand at room temperature ~or 24 hours and is vacuum filtered. The filtrate is concentrated in vacuo and the residue orange semi-solid is slurried in 50 ml of ether and allowed to stand at room temperature for 24 hours. The suspension formed is vacuum filtered and the filter cake of gold needles is dried to afford 2.45 g (77~ yield) of produc~, m.p. 97-105C.
A sample of the product recrystalllzed from ether affords l-lmino(2-furylmethy')2-(3-carbomethoxy-S~methyl-isothioureido)benzene as a ~luf~y yellow solid, m.p. 94-97C.
~lemental Analysis for Cl5H15~33S: Calc: C,5~-77; H,4.76; N,13.24; S,10.10 Found: C,57 .22; H,4.~4; N,13.60; S,10.43 '~

"`~
'::

- 58 ~

-EXAMPLE 97 - 1-Imino-(p-chlorophenyl)methyl-2 (3-carbo-methoxy-S-methylisothioureido)-4-propylthio-benzene . ~
To a mixture of l-imino-(~-chlorophenyl)-methyl-2-(3-carbomethoxythioureido)-4-propylthiobenzene (4.22 ~.;
.01 mol) in acetone (25 ml.) and water (10 ml.) there i~
added 5~% aqueous sodium hydroxide (0.8 g.; .01 mol). The mixtu~e is stirred at room temp~rature ~or one hour and to it thers is ad~ed dimethyl ~ulfate (1.26 ~.; oOl mol). The reactlon m~xture is stirred at room temperature for one hour and the precipitate collect3d and dried to a~ford 1 imino-~p-chlorophenyl)methyl-2-(3-carbometho~y-S-meth~lisothio-ureido)-4-propylthiobenæene.
EXAMPLE 98_ 1-Imino~henylmethyl-2-(~-carbomethoxy~S-methyl-othioursido)-4-propylthiob3nz3ne _ _ _ To a 301ution o~ 1-iminophenylmethyl-2-~-carbo-metho~ythioureido)-4-propylth~obanzen3 (~.88 g.; .01 mol) ln acetone (40 ml.) and water (10 ml.) there is a~ded calcium hydroxide (0.74 g.; .01 mol). The mi~ture is ~tirred at room temperature ~or 4 hours and then i~ added methyL iodide (1.42 g.; .01 mol). The mixture is ~tirred at room t~mpera-ture for 4 hour~ and the prscipitate collected ~nd dried to ~ford 1-iminophen~lmethyl-2-(3-carbomethoxy-S-meth~lisothio-ureido)-4-propylthiobenzene.
EX~MPLE ~- l-Iminophenylmethyl-2~ carbomethoxy-S-methyl-To a so~ution o~ l-im~noph~nylmethyl~ -carbo- -methoxythioureido3-4-propylthiobenz~ne (3.88 g.; .01 mol) in dimethylformamide (40 ml9) and water (10 ml.) there i9 added calcium hydro~ide (0.74 g.; .01 mol). The mixture is tirred at roo~ temperature for fou~ hourQ and to it there i~ added dimethy'sulfate (~26 g.). The mixture is stirred at room I
.. ~ . .

2? ~

temperature for fou~ hours and the precipitate collected and dried to afford l-imin~phenylmethyl-2-~3-carbomethoxy-S-methylisothioureido)-~-propylthi3benz~e.

EXAMPLE 100- 1-I~ino-(o-chlorophenyl)methyl-2-(3-carbo-~ ~ methoxy-S-methyli~othioureido) 4-propylthio-benzene To a mixture of l-imino-(o-chloroph~nyl)methyl-2-(3-carbomethoxythioureido)~ propylthiobenzene (4.22 g.;
.01 mo') in acetone (25 ml.) and water (10 ml.) there is

10 added 50~ aqueous sodium hydrexide (o.8 g.; .01 mol~. The mixture is stirred at room temperature ~or one hour and there is then added dimethy~ sulfibe (1.1 ~.; .01 mol). The mixture is stirred at room temperature for 3 hours and ths precipi-tate collected and dried to af~ord 1-imino-(o-chlorophenyl)-15 methyl-2-(3-carbomethoxy-S~methylisothioureido)-4 propylthio-benzene.
EXAMPLE 1~ Imlnophenylmethyl-2-(3-carbomethoxy-S-m~thyl-i~othioureido)-5-benzoylbenz~ns To a ~olutlon of l-iminophenylmethyl-2-(3-carbo-20 methoxythioureido)-5-benzo~lbenzene (4.33 g.; .01 mol) in di-mQthyl~ormamide (50 ml.) and water ~5 ml.) there is added calcium hydroxide (0.74 g.; .01 mol). The mixture is stirred at 30C. for 2 hours and to it ~here ls added dimethyl sulfite (1.1 g.; .01 mol). The mixture is stirred at room te~perature 25 for 3 hours and the pr cipitate collect~d and dried to a~ford 1 iminophenylmethyl-2-(3-carbomethoxy-S-methyli30th~0ure1do)-5-benzoylbenzene.
EX~MPLE 102- l-Imlno-(p-chlorophenyl)msthyl-2-(3-carbo-methox~-S-methylisothioureido)-4-phenylthio-~o benzRne , . . .
To a mixture o~ l-imino-(p chlorophenyl)-methyl-2-(3-carbomethoxythioureido)-4-phenylthiobenæ~ne (4.56 g.;
.01 mol~ in acetone (~5 ml.) there i~ added 57 ~ 6 .. ~.~, . ".

sodium hydride (0.42 g.; oOl mol) (oil dispersion).
~he mixture is stirred at room temperature ~or one hour and there is then added methyl iodide (:L.42 g.; ~01 mol).
The mixture is stirred at room temperature for o~e hour and is poured into an excess of water. The suspensio~
is filtered and the precipitate dried to afford l-imino-(P-chlorophenyl)methyl-2-(3-car~omethoxy-S-meth~lisothio~
ureido)-~-phenylthiobenzene.
E~4MPT~ 103- 3-Imino-(o-chlorophenyl)methyl-~-(3-carbo-.10 methoxv-S-methYlisothioureido)benzo~henore To a mixture of 3-imino-(o-chlorophenyl)methyl-4-(3-carbomethoxythioureido)benzophenone (4.52 gO; .01 mol) ~
in 1,2-dimethoxyethane (50 ml.) there is added 57% sodium ;
h~dride (0.42 g.; .01 mol) (oil dispersion). The mixture is stirred at room temperature for one hour and there is then added dimethyl sul~ate (1.26 g.; .01 mol). The mix-ture is stirred at room temperature for one hour and is poured into an excess of water. The suspension is filtered and the filter cake d~ied to afford 3-imino-(o-chlorophenyl)methyl-~-(3-carbomethoxy-S-methylisothioureido~
benzophenone.
E~MPLE 104- 3-Imino-~o-nitrophenyl~methyl-~-(3-carbomethox~-S-metlhlLlgg~h___ r~ido)benzo~helg~
To a mixture of 3-imino-(o-nitrophenyl)methyl-~-(3-ca~bomethoxythioureido)benzophenon~ (4.62 g.; .01 mol~
in dimethyl formamide ~0 ml.) there is added 57~ sod~um h~Jdride to.42 g.; oOl mol) (oil dispersion). The mixture is stirred at room temperature for one hour and to it there is added dimethyl sulfi~ (1.1 g.; ~01 mol~ The ; 3~ mixture is stirred at room temperature ~or 1-l/2 hours and is poured into an excess of water~ The suspension ~ ~ .

formed is vacuum filtered and the filter caked dried to afford 3-imino-(o-nitrophenyl)methyl-~-(3-carbo~ethoxy-S-methylisothioureido)benzophenone~
EXAMPLE 105_ 3-Imino-(3,~-dichlorophenyl)methyl-~-(3-~ ioureido~benzo~henone To a mixture of 3-imino-(3,4-dichlorophenyl)-methyl-~-(3-carbomethoxythioureido)benzophenone (4~86 g.;
.01 mol) in acetone (50 ml.) there is added calcium hydride (0.~2 g.; .01 mol). Th~ mixture i~ refluxed for one hour and then cooled to room temperature. To the mixture is added me~hyl iodide (1.42 g.; .01 mol).
The mixture is s~irred at room temperature for one hour and is poured into an excess of ice water. The suspension formed is filtered and the filter cake dried to afford 15 3-imino-~3,4-dichlorophenyl)methyl ~-(3 carbomethoxy-~- i methylisothioureido)benzophenone.
EXAMPL~ - 3-Imino-(4-methoxyphenyl~methyl-4-(3-carbomethoxY-S-meth~li~othio reido)benzo~h~none To a mixture of 3-imino-(4 methoxyphenyl~methyl-1t-(3-carbomethoxythioureido)benzophenone (4.47 g.; ~01 mol) in l,2-dimethoxyethane (50 ml.) there is added calcium hydride (0.42 g.; .01 mol)n The mixture is refluxed ~or one hour and is cooled to room temperature. To the mixture ~ -there is added dimethylsulfate (1.26 g.; oOl mol)O The mixture is stirred at room temperature for one hour and is poured into an excess of ice water. The suspension ~ormed is filtered and the filter cake dried to afford 3-imi~o- ;
(~-methoxyphe~yl)methyl-~-(3-carbomethoxy-S-methyliso-thioureido)benzcphenone.
' ' ., ~, ., :. ., EXAMPLE ~7- 3-Imino-(~-nitrophenyl)methyl-~-(3-carbo-~~ m To a mixture o~ 3-imino-(4-nitrophenyl~-methyl-~-(3-carbometho~Jthioureido)benzophenonQ (4~62 g.;
.01 m~l) in acetone t50 ml.) there is added calcium hydride (0.~2 g.; .01 mol). The mixture is refluxed for one hour and is cooled to room temperal;ure. ~o the mixture there is added dimethylsulfite (l.l g~; oOl mol). $he mix-ture is stirred at room temperature for one hour and is poured into an excess of ice water. The 3uspension formed .... .
~s filtered and the filter cake dried to afford 3-imino~
(4-nitrophenyl)methyl-~-(3-carbomethoxy-S methy]isothio-ureido)benzophenone. ;

EXAMPLE108 - 1-Iminophenylmethyl-2-~3-carbomethoxy-S-meth~lisQthioureido~-4-Pro~lthiobenzene To a mlxt~lre of 2-(3-carbomethoxy-S-methyl-isothioureido)-~-propylthloaniline (3.13 g.; .OI mol) in methanol (25 ml.), cooled to 5C., there is added ~enz- -aldehyde (1.06 g.; 0.1 mol). The mixture is stirred at room temperature for one hour and is filtered. The filter cake is dried to afford l-iminophenylmethyl-2-(3-carbo-methoxy-S-methylisothiouraido)-~-propylthiobenzene.

EX~MPLE 109- 1-Imino-(~-chlorophenyl)methyl-2-(3-carbo-methoxy-S-methylisothioureido)-~-phenylthio~ ~
aniline _ _ _ _ 7 To a mlxt~lre of 2-(3-carbomethox~-S-methyliso-thioureido)-4-phenylthioaniline (~.55 g~; ~01 mol) in -~
methanol (25 ml~3, cooled to 5C., is added p-chlorobenz-aldehyde (1.4 g.; .01 mol~ ~ollowed by concentrated ~ulfuric :;.. . .
acid (3 drops). T~ mi~ture is stirred at 5C. for one - hour and is then vacuum filtered. ~he fi}ter ca~e is dried to afford l-imino-(~-chlorophenyl~methyl-2-(3-carbo-methoxy-S-methylisoth~oureido)-~-phenylthioanllin~O
: ~! 63 : ~ . . . . ., .... . . .. :

~- 3-Imino-(~-nitrophenyl)methyl-4-(3~carbo-m~thox~-s-methy~lisothiour~i~)ber~ o~cs-~ o a ~ixture of 3-amino-~-~3-carbo~etho~-S-methylisothioureido)benzophenone (3.~3 gY.; .01 mol) in benzene (100 ml.) there ia added ~-nitrobenzaldehyde (1.5 g.; .01 mol). The mixtu~e is re~luxed and stirred for 3 hoursO Wate~ of the reaction is removed by a Dean-Stark distillation receiver. ~he mixture is pou~ed into a~
excess of haxane ana the suspension formed is vacuum -~iltered~ The filter cake is dried to afford 3-imino~
nitrophenyl)methyl-~-(3-carbomethoxy-S-methylisothio-ureido)benzophenone.

EXAMPLE 111- 3-Imino (~-methoxyphenyl)~ethyl-4-(3 carbo-methox~-S-methYlisoth ou eido~e~ 3a~a~-To a mixture of 3-amino-~-(3-car~omethoxy-S-methylisothiou-eido)benzophenone (3.43 g.; .01 mol) in benzene (100 ml.) there is added p-methoxybenzaldehyde (1~36 g~; .01 ~ol) and P-toluenesul~niC acid mono-hydrate (0.1 g.). The mixtu~e is refluxed and stirred for 3 hours. ~he water reaction is removed by a Dean-Stark d$stillatlon receiver. The mixture is poured into an e-~cess of hexane and the suspen~ion formed is filtered.
~he filter cake is dried to afford 3-imino-(4-methoxy-phenyl)m~thyl-~-t3-carbomethox~-S-met'nyli~thioureido)-benzophenone.

~_ 2- 1-Imi~ophenylmethyl-2-(3-carbometho~y-S-methylisothioureido)~-a-propylsulf`iIlyl- .:

To a solution of l-iminophe~lmethyl-2-~3-carbomethoxy-S-methylisothioureido)-~-n-propylthiobenzene (~.02 g.; .01 mol) in met~ylene chloride (50 ml,.), coolsd ; to -5~ c~, is added 85% of m-chloroperoxybenzoic acid -:

. . . . . . . . . . .

(2.02 g.; .01 mol). The mixture is stirred at -5C. for 30 minutes and is washed with aqueous sodium bicarbonate solution. The methylene dichloride is evaporated from the organic solu~ion to afford l-iminophenylmethyl~2~(3-carbomethoxy-S-methylisothioureido)-~-n-propylsulfinyl-benzene.

EXAMP~E 113- 1-Iminophenylmethyl-2-(3-carbomethoxy-S-methylisothioureido)-4-n-propylsulfonylbenzene . ~
To a solution of 1-iminophenylmethyl-2-(3-carbomethoxy-S-methylisothioureido)-4-n-propylthiobenzene (4.02 g.; .01 mol) in methylene chloride (50 ml.), cooled to -5co ~ is added m-chloroperoxybenzoic acid (4004 g.;
.02 mol). ~he mixture is stirred ~t room temperature ~or 2 hours and is washed with aqueous sodium bicarbonate solution. The methylene dichloride is evaporated from the organic mixture to afford l-iminophenylmethyl-2-(3 carbo~
methoxy-S-methylisothioureido)-~-a-propylsulfonylbenzene.
EX~MP~E 114- 1-Iminopropyl-2-(3-carbomethoxy-S-methvl,isothioureido)~ ro~lthiobenzene Step A- l-Iminopropyl-2-(3-carbomethoxy-thioureido?-4-~ro~ylthiobenzene To a suspension of 2--(3-carbomethoxy-thioureido)-4-propylthioaniline (2.99 g.; .01 mole) in methanol (50 ml.), cooled to 5C., there is added p~opion-aldehyde (0.6~ g.; .01 mole). ~he mixture is stirred at 5C. for 2 hours and the solution ~ormed is stirred at room temperature fQr 1 week~ The suspension that forms is vacuum filtered and the filter cake is washed with ether and dried to afford l-iminopropyl-2-~3-carbomethoxy-thioureido~-4-propylthiob~nzene (1.3 g.; 3803%), m.p.
153-168 C. (dec.).
, .

,, ~ .

~ , El~men~al ~alysiS for ClsH21N302S2 Calc.: C, 53.07; H, 6.24; N, 12.38 Found: C, 52.72; X, 6.32; ~, 12.38 Ste~ B - l-Iminopropyl-2-~3-carbometh~xy-S-methylisothiour ido)-~-propylthio-benzene To a suspension of l-iminopropyl-2-(3-carbomethoxythioureido)-4~propylthiobenz~ne (1 g.;
.00295 mole) in acetone ~30 ml~) and water (L5 ml.) there is added 50.8% aoueous sodium hydroxide (0.23 g.; .002~5 mole). The solutio~ that forms is stlrred at room ;
temperature for one hour and ~o it there is added methyl ioAide (0~42 g.; .00297 mole). ~he turbid solutlon formed is stirred at room tsmperature ~or 30 mi~utes a~ld is 15 poured lnto water ~500 ml.). The suspension formed is ;
stirred at room temperature ~or one hour ar.dis vaculIm filtered. The filter cake is d-ied to afford l-imino~
propyl-2-(3-carbomethoxy-S-methylisothioureido~
pFopylthiob~nz~ne (0.85 g.; 81.5%) ? m.p. 85 90C. (dec.).
Elemental analysis for C16H23N302S2 Calc.: ~, 54.36; H, 6.50; N, 11.8q Found: C, 53.96; H, 6.60; N, 11.63 EXAMPLE 115 - l-Imino (4-methyl)phenylmethyl-2-(3carbo-methoxy-S-methyllsothioureido)-4-propyl-25 ~ thiobenzene Step A - l-I~ino(4-methyl)phenylmethyl-2-(3-carbo- -~
methoxythioureido 4-propylthiobenzene To a suspension of 2~(3-carbomethoxythioureido)-4-propylthioaniline (9.0 g; .03 mole) in methanol (100 ml), cooled to 10C, there is a~ded ~-methylbenzaldehyde (3.5 g;
.03 mole). The mixture is stirred at 10C ~or :L hr. and ~:
.

. " ,:

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

%~

at room temperature for 18 hrs. The suspension that ~orms is vacuum filtered and the filter cake is air dried to afford l-imino(4-methyl)phenylmethyl-2-(3-carbomethoxy-thicureido)-4-propylthiobenzene ~10.75g; 89%), m.p. 135-141C.
Elemental Analysis for C20H23N3O2S2 Calc: C, 59.82; H, 5.77; N, 10.46 Found: C, 59.32; H, 5.87; N, 10.75 St~ B - l-Imino(4-methyl)phenylmethyl-2-(3-carbo-methoxy-S-methylisot~ioureido~-4-propyl-thiobenzene _ ___ _ _ To a suspension of l-imino(4-methyl)phenylmethyl-2-(3-carbomethoxythioureido)-4-propylthiobenzene (4.02 ~;
.01 mole) ln acetone (60 ml) and water (20 ml) there is added 50~ aqueous sodium hydroxide (0.8 g; .01 mole). The ~ solution that forms within 10 min. is stirred at room ; temperature for 50 min. and to it there is added methyl iodide (1.42 g, .01 mole). The suspension that forms is stlrred at room temperature for 1 hr. and is vacuum filtered, The filter cake is air dried to afford l-lmino(4-methyl)-phenylmethyl-2-(3-carbomethoxy-S-methyl isothioureidoj-4- ~
propylth~obenzene (3.6 g; 86.6%), m.p. 113-115C. ~ -. .
Elemental analysls for C21H25N302S2 Calc: C, 60.69; H, 6.06; N, 10.11 Found: ~, 60.75, H, 6.29; N~ 10~47 . .
EXAMPLE 116 - 1-Imino-(4-methoxy)phenylmethyl-2-(3-carbo-methoxy-S-methylisothioureido)-4-propylthio-Step A - 1Imino-(4-methoxy)phenylmethyl-2-~3-3 ~ carbom~ _ido~ -4-propylth~oben_ene .~ To a suspension of 2~(3-carbomethoxy thioureido)~4- :-propylthioaniline (9.0 ~;; .03 mole) in methanol (100 ml) ~ .
.

~. .
~, . , , ii2 ~

cooled to 10C, there ~s added ~=anisaldehyde (4.38 g;
.03 mole). The mixture is stirred at 10C for 1 hr. and at room temperature for 18 hrs. The suspension that forms is vacuum filtered and the filter cake air dried to afford 1-lmino-(4-methoxy)phenylmethyl-2-(3-carbomethoxythioureido) 4-propylthiobenzene (9.9 g,;7g%), m.p. 141-144C..
Elemental analysis for C20H23N303S2 Calc: C, 57.53; H, 5.55; N, 10.06 Found: C, 57.19; H, 5.67; N, 10.25 Ste~ B - l-Imino-(4-methoxy)phenylmethyl-2-(3-carbo-methoxy-S-methyllsothioureido)-4-propyl-thiobenzene _. . .
To a suspension of l-imino-(4-methoxY)PhenYlmethYl-2-(3-carbomethoxythioureldo)-4-propylthiobenzene (4.18 g;
.01 mole) in acetone (60 ml) and water (20 ml) there ls added 50% aqueous sodium hydroxide (.o8 g; .01 mole). The solution that forms w~thin 10 min. is stirred at room temperature for 50 min. and to it there is added methyl iodide (1.42 g; .01 mole). The suspension that fcrms is stirred at room temperature for 1 hr. and is ~acuum ~lltered. The filter cake ls alr drled to af~ord l-imino-(4-methoxy)phenylmethyl~2~(3-carbomethoxy-S methylisothio-ureido)-4-propylthiobenzene (2.3 g; 53~0), m.p. 90-92 Elemental analysis for C21H25N303S2 Calc: C, 58.44; H, 5.84; N, 9.74 Found: C, 58.38; H, 5.94; N, 9o91 EXAMPLE 117 - 1-Imino(4-nitro)phenylmethyl-2-(3-carbo-methoxy-S-methylisothioureido)-4~propylthio-benzene _ _ 3~ Ste~ A - l-Imino (4-nitro)phenylmethyl-2-(3-carbo-; methoxythioureido)-4~propylthiobenzene ~;
To a suspension of 2-(3-carbomethoxythioureido)-4-propylthioaniline (4~0 g; .013 mole) in methanol (35 ml) ~ .
r3~ ~ 6 8 ~L .~. I
.. . . ' ' "'' ' ~

there is added a solution of p-nitrobenzaldehyde (2.0 g;
.013 mole) in methanol (35 ml). The mixture is stlrred at room temperature for 1 hr. and is vacuum filtered. The ~ilter cake ls washed with methanol and dried to a~ford 1-imino(4-nitro)phenylmethyl-2-(3-carbomethoxythioureido)-4-propylthiobenzene (5.3 g; 94%), m.p. 198-200C.
; Elemental analysis ~or Cl9H20NLIO4S2 Calc: C, 52.76, H, 4.66; N, 12.95; S, 14.83 Found: C, 52.85; H, 4.79; N, 13.39; S, 14.84 Step B - l-Imino-(4-nitro)phenylmethyl-2-(3-carbo-; methoxy-S-methylisothioureido)-4-propyl-~hlobenzene A mixture of l-imino-(4-nitro)phenylmethyl-2-(3-carbomethoxythioureido)-4-propylthiobenzene (4.3 g; .01 mole) acetone (50 ml), water (25 ml) and 50% aqueous sodium hydroxide (0.8 g; .01 mole) is stirred at room temperature for 15 min. and is cooled to 12C. To the mixture there is added methyl iodide (1.4 g; .01 mole) and it is stirred at 13C to 20C for 2 hrs. The suspension th~ ~orms is vacuum filtered and the fllter cake is washed with acetone and dried to afford l-imino(4-nltro)phenylmethyl-2-(3-; carbomethoxy-S-methyllsothloureldo)-4-propylthiobenzene (3~5 g; 78~o)~ m.p. 135-137C dec.
Elemental analysis for C20H22N404S2 Calc: C, 53~79; H~ 4.97; N, 12.55; S, 14.36 Found: C, 53.39; H, 4.97~ N, 12.60; S, 14.69 EXAMPLE 118 - 1-Imino-(2-furylmethyl)~2-(3-carbomethoxy-S-methylisothioureido)-4-~ro~ylthiobenzene Imino-(2-furylmethyl)-2-~3-carbomethoxy-thioureido)-4-pro~ylthiobenzene To a suspension of 2-(3-carbomethoxythioureido)-4-propylthioaniline (6.0 g; .02 mole) in methanol (200 ml), , ~'. , .

cooled to 10C there is added 2-furfuraldehyde (1.92 g, .02 mole). The mixture is stirred at 10C for 1 hr. and at room temperature for 18 hrs. The suspension formed is vacuum filtered and the filter cake is air dried to afford 1-imino(2-furylmethyl)-2-(3-carbomethoxythiouriedo)-4-propyl-thioanil~ne (5.6 g; 74%), m.p. 131-133C.
Elemental analysis for C17HlgN3O3S2 Calc: C, 54.09; H, 5.07; N, 11.13 Found: C, 53.68; H, 5.11; N, 11.13 Step B l-Imino-(2-furylmethyl)-2-(3-carbomethoxy-S-methylisothioureido)-4-~ropylthiobenzene To a suspension of l-imino-(2-furylmethyi)-2-(3-carbomethoxythioureido)-4-propylthiobenzene (3.77 g; .01 mole) in acetone (45 ml) and water (15 ml) there is added 50~ aqueous sodium hydroxide (0.79 g; .01 mole). Within 15 min. after addition a solution forms and is stirred at room temperature for 30 min. To the solution there is added methyl iodide (1.42 g; .01 mole). The mixture is stirred at room temperature for 1~3/4 hrs. and the sus-pension that forms is vacuum filtered. The filter cake is air dried to afford 1-imino-(3-furylmethyl)-2-(3-carbo-methoxy-S-methylisothioureido)-4-propyl~hiobenzene (2.65 g;
. .
67.7%), ~.p. 96-98~C.
Elemental analysis for C18H21N33S2 Calc: C3 55.22; H, 5.41; N, 10~73 Found: C, 54.11i H, 5.39, N, 10.51 :

, . .
,;~. .

EXAMPLE_ 119 When the procedures of the above examples are followed and by employing known starting diamine precursors~
~he following products may be obtained: ;
3-iminophenylmethyl-4-(3-carboethoxy S-methylisothioureido)-benzophenone;
3-lmlnot~chloro)phenylmethyl-4-(3-carbopropoxy-S-methyl-isothioureido)benzophenone;
l-iminophenylmethyl-2-(3-carbo-isopropoxy~S-methyli~othio-ureido)-4-propylthiobenzene;
l-iminophenylmethyl-2-(3-carbobutoxy-S-allylisothioureido)-4-phenylthiobenzene;
3-iminophenylmethyl-4-C3-carbo-(2-methoxy)ethoxy-S-methyl-isothioureido]benzophenone;
l-iminophenylmethyl-2-[3-carbo-(2-methoxy)ethoxy-S-methyl-isothioureido~ 4-propylthiobenzene;
3-iminophenylmethyl-4-(3-carbomethoxy-S-methylisothioureido)-4'-chlorobenzophenone;
3 imino-(p-chlorophenyl)me~hyl-4-(3-carbomethoxy-S-allyl-isothioureido)-4t-fluorobenzophenone;
. . .

3-1minophenylmethyl-4-(3-carbomethoxy-S-butylisothioureido)-4'-methylbenzophenone;
3-iminophenylmethyl-4-~3-carbomethoxy-S-benzylisothioureido)-4'-methoxybenzophenone;
3-imino-(o-chloro)phenylmethyl-4-(3-carbomethoxy-S-methyl-isothioureido)-3'-trifluorornethylbenzophenone3 ~.
3-iminophenylmethyl-4-(3 carbomethoxy-S-rnethylisothio-ureido)propiophenone;
3-iminophenylmethyl-4-(3-carbomethoxy-S~allyllsothloureido)-butyrophenone;
~ 3-imino-~-nitrophenylmethyl-4-(3-carbomethoxy-S-butylisothio-: ureido)valerophenone;
l-cyclopropylcarbonyl-3-iminophenylmethyl-4-(3 carbomethoxy-S-methylisothioureido)benzene;
l-cyclopentylcarbonyl-3-imlno~ chloro)phenylrnethyl-4-~3 carbomethoxy S-butylisothioureido)benzene;

.

, . ~
~ 71 ~ .:

1-(2-thienyl) -3-imino-~p-Methyl)phenylmethyl-4-(3-carb methoxy-S-methylisothioureido)benzene;
l-imino~henylmethyl-2-~3-carbomethoxy-S-meth~lisothio-ureido~-4-(4-cyanophenylthio)benzene;
1-imino~henylmethy -2-(3-carbomethoxy-~-butylisothio-ureido~-4-(3 cyanophenylthio)benzene;
l-imino henylmethyl-2-(3-carbomethoxy-S-butylisothio-ureido~-4-(4-methylthiophenylthio)benzene;
l-iminophenylmethyl-2-(3-carbometho~y-S-methylisothio-ureido)-~-(3-methylthiophenylthio)benzene;
1-imino-(p-chlorophenyl)methyl-2~(3-carbomethoxy-S-methyl- -~
isothioureido)-4-(4-acetylphenylthio)benzen_;
l-imino-(P-chlorophenyl)methyl-2-(3-carbomethoxy-S-allyl-isothioureido)-4-(h-msthoxycarbonylphenyithio)benzene;
1~ l-imino henylmethyl-2-(3-carbomethoxy-S-methylisothio-ureido~-4-(4-acetylaminophenyl)benzenQ;
l-imino henylm~thyl-2-(3-carbomethoxy-S-butylisothio-ureido~-4-~4-phenoxyphenylthio)benzene;
1-iminophenylmethyl-2-(3-carbomethoxy-S-methylisothio- .:
: 20 ureido~-4-(4-cyanophenylsulfinyl~benzena;
l-imino-~-chlorophenyl)methyl-2-(3-carbomethoxy-S-butyl-isothioureido~-4-(4-acetylphenylsulfinyl)benzene;
l-iminophenylmsthyl-2-(3-carbo~ethoxy-S-methylisothio-ureido~-4~ cyanophenylsulfonyl)benzene;
l-imino-(P-chlorophenyl)methyl-2-(3-carbomethoxy~s-meth isothioureido)-4-(4-acetylphen~lsul~onyl)benzene;
l-imino-tp-chlorophenyl)methyl-2-(3-carbo~etho~y-S-m~thyl isothioureido)-4 (phenylsulfinyl)benzene;
1-imino-(P-chlorophenyl)m thyl-2-(3-ca L bomethoxy-S-methyl-lsothioureido)-4-(phenylsul~onyl)benzene;
l-imino~ chlorophen~rl)~eth~ 2 ~3-carbomethoxy-S-methyl-~ isothioureido)-5-(~-acetylphenylsulfonyl)benzena;
- l-imino~to-chlorophenyl)meth~J1-2-(3-carbo~ethoxy-S-methyl isothioureido-5~ cyan~phenylsul~onyl)benzene;
1-imino~he~ylmsthyl-2-(3-carbo~ethoxy-S-methylisothio-ureido)-5-(4 acetylphenylsulfinyl)benzene;
l-iminophenylmethyl-2-~3-carbomethox~-S-methyliso~hio-ureido)-5~ -cyanophenylsulIinyl~benzens;

'~ ', ..

~ t l-imino~henylmethyl-2-(3-carbomethoxy-S-methylisothio-ureido)-5-phenoxysulfonylbenzene;
l-(imino-p-chlorophenylmeth-~1)-2-(3-carbomethoxy- S-methylisothioureido)-5-(P-chlorophenoxysulfonyl)benzene;
1-(imino-p-chlorophenylmethyl)-2-(3-carbomethoxy-S-butyl-isothioureido-5-~3-chlorophenoxysulfonyl)benzene;
l-iminophenylmethyl-2-(3-carbomethoxy-S-benzylisothio-ureido-5-(2 chlorophenoxysulfonyl)ben~e;
l-~imino-o-chlorophenylmethyl)-2-(3-carbomethoxy-S-allyl-isothioureido)-5-(3,5-dichlorophenoxysulfonJl)benzena;
l-timino-~-nitrophenylmethyl)-2-(3 carbomethoxy-S-methyl-isothiourei~o)-5-~4-methoxyphenoxysulfonyl)benzene;
1-(imino-P-methoxyphenyl)-2-(3-carbomethoxy-S-methyliso-thioureido)-5-(3-cyanophenoxysulfonyl~benzene;
1-iminophenyl-2-(3-carbometh~xy-S-methylisothioureiio~-5-(3-trifluoromethylphenoxysulfonyl)benzene;
l-iminophenylmethyl-2~(3-carb~methoxy-S-methylisothio-ureido)-5-phenylsulfonyloxybenzene;
l-imino-(~-chlorophenyl)methyl-2-(3-carbomethoxy-S-allyl- ~ -isothioureido)-5-(~-chlorophenyl)sulfon~loxyb0nzene; ~-l-imino-(o-chlorophenyl~methyl-2-(3-carbomethoxy-S-butyl-isothioureido)-5-(3-chlorophen-Jl)sulIonyloxybenzene;
l-iminophenylmethyl-2-(3-carbomethoxy-S-butylisothio ureido)-5-(3,5-dichlorophenyl)sul~on~Jloxybenzene;
1-imino-(P~nitro~henyl)methyl-2-(~-carbomethoxy-S-benzyl- .
isothioureido)-5-(4-methylphenyl)sul~onyloxybenzene;
l-imino-(P-methoxyphenyl~methyl-2-(3-carbomethoxy-S-allyl-isothioureido)-5-(3-tr.~luorophenyl)sulfonyloxybenzene;
l-iminophenylmethyl-2-(3-carbomethoxy-S-methylisothio-ureido)-5-(~-methoxyphenyl)sulfonyloxybenzene.
Examples o~ other X substituents on known diamines include 4-a~d 5-propoxy; ~- and 5-pheno~y; ~-and 5-(pyrid 2-ylo~; 4-(~-chlorophenoxy); ~-~trifluoro-methylphenoxy); 5~(3-chloropropoxy); 5-(2~phe~ylethQxy);
5-~3-phenylprop-2-en-1-yloxyj; 5~ methylphenoxy); 5-(3-methylpheno:~y~; 5-(2-met'nylphenoxy); 5-(3-methylthio-` phe~oxy); 5-(propargylthio); 5-(but-3-en-1-yl-thio);
'~
~73 ~ , .

~' ~
.

5-(but-3-en-1-yl-sulfinyl); 5-(but-3-en-1-yl-sulfonyl);
5-(benzylthio); 5-(benzylsulfinyl); 5-(thiazol-2-yl-thio); 5-(pyrid-2-yl-thio); ~-pyrimidin-2-yl-thio~, ~-(thien-2-yl-thio); 5-(fur-2-yl-thio~; 5-(3-chloro-propylthio); ~-(3-chloropropylthio); ~-(3-chloroprop-2-en-l-yl-thio); 4-(2-cyanoethylthio); 5-(2,3-dichloro-propyl-2-en-1-yl-thio) and the like.
These diamine precursors can be found in U. S. Pat. Nos~ 3,657,267; 3,929,823; 3,929,824; 3,935,209;
3,98~,~61; 3,993,76~; 3,996,35~; 3,99~,369; ~,002,6~0;
....
French Pat. Nos. 2,248,037; 2,270,861 and Netherl~nds Pat.
~o. ~,701,797.

'': ' , . .

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

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

Claims (16)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applying to such plants or to seeds thereof, or to a locus in which said plants are growing, an effective amount of a com-pound of the formula I

wherein R is alkyl, alkenyl, alkynyl, polynuclear aralkyl, mononuclear aralkyl, mononuclear aryloxy lower alkyl, cyclo-alkylalkyl, cyano lower alkyl, hydroxy lower alkyl, aralkenyl, alkoxyalkyl, alkoxycarbonylalkyl, phthalimido lower alkyl or phenoxycarbonylalkyl; R1 is alkyl or lower alkoxyalkyl;
R2 is alkyl or substituted or unsubstituted aryl; and X is hydrogen, nitro, halo, lower alkoxy, lower alkanoyl, lower alkyl, thiocyanato, a radical of the formula: Y-S(0)n wherein Y is lower alkyl, lower alkenyl, cyclo lower alkyl, pyridyl, thienyl, furyl, pyrimidyl or thiazolyl, or mono-nuclear aryl, and n is an integer of 0 to 3, X is also lower alkyl carbonylamino, lower alkoxy carbonylamino, cycloalkyl-carbonylamino, a radical of the formula:

wherein Y' is mononuclear aryl, cyclo lower alkyl, pyridyl, thienyl, furyl, pyrimidyl or thiazolyl, or a radical of the formula: Y"O wherein Y" is lower alkyl, lower alkenyl, mono-nuclear aralkyl or pyridyl, thienyl, furyl, pyrimidyl or thiazolyl; or a nontoxic pharmaceutically acceptable acid addition salt or amide thereof.

2. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applying to such plants or to seeds thereof, or to a locus in which said plants are growing, an effective amount of a com-pound of the formula Ia wherein R3 is lower alkyl, lower alkenyl, lower alkynyl, benzyl, 2,6-dichlorobenzyl, phenethyl, cycloalkyl lower alkyl, phenoxy lower alkyl, cyano lower alkyl, lower alkoxy carbonyl lower alkyl, phthalimido lower alkyl, phenyl lower alkenyl or hydroxy lower alkyl; R4 is lower alkyl; R5 is mononuclear aryl of from 4 to 6 nuclear carbon atoms, polynuclear aryl of from 10 to 14 nuclear carbon atoms or heteroaryl of from 5 to 6 nuclear atoms and containing from 1 to 3 hetero atoms selected from oxygen, nitrogen and sulfur, and x1, is hydrogen, lower alkyl carbonylamino, lower alkoxy carbonylamino, lower alkoxy, propylthio, propoxysulfonyl, propylsulfonyloxy, propylsulfinyl, propylsulfonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, lower alkanoyl or benzoyl.

3. A method of combatting or preventing fungal in-fections in plants subject to such infections which comprises applying to such plants or to seeds thereof, or to a locus in which said plants are growing, an effective amount of a compound of the formula Ia as recited in claim 2 wherein R5 is nitro-phenyl, dimethylaminophenyl, lower alkoxyphenyl, cyanophenyl acetamidophenyl, methylenedioxyphenyl, phenyl, halophenyl, furyl, thienyl, lower alkyl phenyl or dihalophenyl.

4. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applyong to such plants or to seeds thereof, or to a locus in which said plants are growing, and effective amount of a compound of the formula Ia as recited in claim 2 wherein X1 is hydrogen, 4-benzoyl, 5-propylthio or 5-phenylthio.

5. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applying to said plants or to seeds thereof, or to a locus in which said plants are growing, and effective amount of the compound named 3-imino-phenylmethyl-4-(3-carbomethoxy-S-methyl-isothioureido) benzophenone.

6. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applying to said plants or to seeds thereof, or to a locus in which said plants are growing, and effective amount of the compound named 3-imino-(4-chlorophenyl)methyl-4-(3-carbomethoxy-S-methylisothioureido) benzophenone.

7. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applying to said plants or to seeds thereof, or to a locus in which said plants are growing, an effective amount of the compound named 1-iminophenylmethyl-2-(3-carbomethoxy-S-methylisothioureido)-4-propylthiobenzone.

8. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applying to said plants or to seeds thereof, or to a locus in which said plants are growing, an effective amount of the compound named 1-imino-(p-chlorophenyl)methyl-2-(3-carbomethoxy-S-methylisothioureido)-4-phenylthiobenzene.

9. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applying to said plants or to seeds thereof or to a locus in which said plants are growing, an effective amount of the compound named 1-imino-(p-chlorophenyl) methyl-2-(3-carbomethoxy-S-methylisothioureido)-4-propylthio benzene.

10. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applying to said plants or to seeds thereof, or to a locus in which said plants are growing, an effective amount of the compound named 1-imino-(2-furylmethyl)-2- (3-carbomethoxy-S-butylisothioureido)-benzene.

11. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applying to said plants or to seeds thereof, or to a locus in which said plants are growing, an effective amount of the compound named 1-imino-(2-furylmethyl)-2-(3-carbomethoxy-S-benzylisothioureido)-benzene.

12. A method of combatting or preventing fungal infections in plants subject to such infections which comprises applying to said plants or to seeds thereof, or to a locus in which said plants are growing, and effective amount of the compound named 1-imino-(2-furylmethyl) 2- (3-carbomethoxy-S-methylisothioureido)-benzene.

13. A method as in claim 1, wherein said compound of Formula I is applied to said plants or to seeds thereof, or to a locus in which said plants are growing, in combination with anothar fungicide.

14. A method as in claim 2 wherein said compound of Formula Ia is applied to said plants or to seeds thereof or to a locus in which said plants are growing, in combination with another fungicide.

15. A method of controlling the growth of fungi in an environment or on a substrate which is subject to deterioration due to attack by said fungi, which comprises applying to said environment or to said substrate an effective amount of a compound of the formula I

wherein R is alkyl, alkenyl, alkynyl, polynuclear aralkyl, mononuclear aralkyl, mononuclear aryloxy lower alkyl, cycloalkylalkyl, cyano lower alkyl, hydroxy lower alkyl, aralkenyl, alkoxyalkyl, alkoxyearbonylalxyl, phthalimido lower alkyl or phenoxycarbonylalkyl; R1 is alkyl or lower alkoxyalkyl; R2 is alkyl or substituted or unsub-stituted aryl,and X is hydrogen, nitro, halo, lower alkoxy, lower alkanoyl, lower alkyl, thiocyanato, a radical of the formula: Y-S(O)n wherein Y is lower alkyl, lower alkenyl, cyclo lower alkyl, pyridyl, thienyl, furyl, pyrimidyl or thiazolyl, or mononuclear aryl, and n is an integer of 0 to 3, X is also lower alkyl carbonylamino, lower alkoxy carbonylamino, cycloalkylcarbonylamino, a radical of the formula:
Y"?- wherein Yr is mononuclear aryl, cyclo lower alkyl, pyridyl, thienyl, furyl, pyrimidyl or thiazolyl, or a radical of the formula:
Y"O wherein Y" is lower alkyl, lower alkenyl, mononuclear aralkyl or pyridyl, thienyl, furyl, pyrimidyl or thiazolyl; or a non-toxic pharmaceutically acceptable acid addition salt or amide thereof

16. A method of controlling the growth of fungi in an environment or on a substrate which is subject to deterioration due to attack by said fungi, which comprises applying to said environment or to said substrate an effective amount of a compound of the formula Ia wherein R3 is lower alkyl, lower alkenyl, lower alkynyl, benzyl, 2,6-dichlorobenzyl, phenethyl, cycloalkyl lower alkyl, phenoxy lower alkyl, cyano lower alkyl, lower alkoxy carbonyl lower alkyl, phthalimido lower alkyl, phenyl lower alkenyl or hydroxy lower alkyl; R4 is lower alkyl; R5 is mononuclear aryl of from 4 to 6 nuclear carbon atoms, polynuclear aryl of from 10 to 14 nuclear carbon atoms or heteroaryl of from 5 to 6 nuclear atoms and containing from 1 to 3 hetero atoms selected from oxygen, nitrogen and sulfur, and X1 is hydrogen, lower alkyl carbonylamlno, lower alkoxy carbonylamino, lower alkoxy, propylthio, propoxysulfonyl, propylsulfonyl oxy, propylsulfinyl, propylsulfonyl, phenylthio, phenyl-sulfinyl, phenylsulronyl, phenoxysulfonyl, phenylsulfonyl-oxy, lower alkanoyl or benzoyl,