GB1602009A - Isothiourea derivatives - Google Patents

Description

(54) ISOTHIOUREA DERIVATIVES (71) We, ROHM AND HAAS COMPANY, a corporation organised under the laws of the State of Delaware, United States of America, of Independence Mall West, Philadelphia, Pennsylvania 19105, United States of America, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention concerns 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.

British Pat. Nos. 1,214,415 and 1,307,250; U.S. Pat. Nos. 3,958,008; 3,860,586 and 3,836,569 and Netherlands Patent Specification No. 7,401,797 disclose numerous thioureas useful as anthelmintics, though none have a substituent on the sulfur. German Pat. No. 2,303,048 discloses 2-acylated amino-S-substituted isothioureidobenzenes as anthelmintics. However, there are no references disclosing compounds having both an imino substituent 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. 1,350,277.

The novel 2-imino substituted isothioureidobenzenes (I, infra) of this invention have the following structural formula:

wherein R is alkyl (e.g. (C1-C8)alkyl such as methyl, ethyl, n-propyl, n-butyl, iso butyl, sec-butyl, pentyl, hexyl, heptyl or octyl), alkenyl (e.g. (C3-C8)alkenyl such as propenyl, butenyl, pentenyl, hexenyl, heptenyl or octenyl), alkynyl (e.g. (C3- C8)alkynyl such as propynyl, butynyl, pentynyl, hexynyl, heptynyl or octynyl) 2,6 dichlorophenyl, optionally substituted (usually in the aryl portion), aralkyl (e.g. naphthylmethyl, naphthylethyl, phenanthrenylmethyl, benzyl, phenethyl or phenylpropyl which may be ring-substituted - with from 1 to 3 groups such as halo (viz. chloro, iodo, bromo or fluoro), alkyl, alkoxy, nitro or cyano), mononuclear aryloxy(C3-C8)alkyl (e.g. phenoxy(C3-C6)alkyl such as phenoxypropyl. phenoxybutyl, phenoxypentyl or phenoxyhexyl), cycloalkylalkyl (e.g. cycloalkyl(C1C6) alkyl of from 5 to 6 nuclear carbon atoms such as cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl or cyclohexylethyl), cyano(C3-C6)alkyl (e.g. cyanopropyl, cyanobutyl, cyanopentyl or cyanohexyl), hydroxy (C3-C8)alkyl (e.g. hydroxypropyl, hydroxybutyl, hydroxypentyl or hydroxyoctyl), aralkenyl (e.g. poly- and mononuclear aralkenyl such as phenylpropenyl), alkoxyalkyl (e.g. alkoxyalkyl, having up to 3 carbon atoms in the alkoxy group and up to 4 carbon atoms in the alkyl group such as methoxypropyl, ethoxypropyl, methoxybutyl or propoxybutyl), alkoxycarbonylalkyl (e.g. alkoxycarbonyl alkyl having up to 3 to 6 carbon atoms in each of the alkoxy and alkyl groups (e.g. methoxycarbonylpropyl, ethoxycarbonylbutyl, ethpxycarbonylpentyl or propoxycarbonylhexyl), phthalimido (C1-C,,)alkyl (e.g. as phthalimidobutyl) or phenoxycarbonylalkyl (e.g. phenoxycarbonyl (C3-C6)alkyl such as phenoxycarbonyl propyl, phenoxycarbonylbutyl, phenoxycarbonylpentyl or phenoxycarbonylhexyl); Rl is alkyl (e.g (C1-C6)alkyl such as methyl, ethyl, npropyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, pentyl or hexyl), cycloalkyl or alkoxyalkyl having 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties (e.g. methoxyethyl ethoxyethyl or propoxyethyl); R2 is aikyl (e.g. (C1-C6)alkyl), substituted or unsubstituted aryl (wherein the aryl group may be a mononuclear aryl group such as phenyl or a polynuclear aryl group of 10 to 14 carbon atoms) or optionally substituted heteroaryl (preferably of from 5 to 6 nuclear atoms and containing from 1 to 3 heteroatoms selected from oxygen, nitrogen or sulfur); and X is hydrogen, nitro, halo, alkanoyl of from 2 to 5 carbon atoms (e.g. acetyl, propionyl, butyryl or pentanoyl), alkyl (preferably from 1 to 4 or 6 carbon atoms such as methyl, ethyl, propyl or n-butyl) thiocyanato, alkylcarbonylamino having 1 to 6, e.g. 1 to 4, carbon atoms in the alkyl group (e.g. methylcarbonylamino), alkoxycarbonylamino (e.g. (C1-C4)alkoxyamino such as methoxy carbonylamino or isopropoxycarbonylamino), cycloalkylcarbonylamino (usually having 5 or 6 cyclic carbon atoms, e.g. cyctopentylcarbonylamino or cyclohexylcarbonylamino) a radical of the formula: YS(O)n [wherein Y is alkyl (preferably of from 1 to 5 carbon atoms; alkenyl (preferably C3-C6), alkynyl (preferably C3-C6), cycloalkyl (preferably of 3 to 7 carbon atoms), a 5- or 6-membered heterocycle (e.g. pyridyl, tienyl, furyl, pyrimidyl or thiazolyl) or mononuclear aryl (e.g. phenyl) and n is 0 to 3], a radical of the formula:

[wherein Y' is an optionally substituted group selected from mononuclear aryl (e.g. henyl), cycloalkyl (preferably of 3 to 7 carbon atoms, and a 5- or 6-membered heterocycle (e.g. as pyridyl, 2-thienyl, or furyl)] or a radical of the formula: Y"O- [wherein Y" is an optionally substituted group selected from alkyl (preferably C1- C5 such as methyl, ethyl, propyl, butyl or pentyl), mononuclear aryl (e.g. as phenyl) alkenyl (preferably C3-C8), mononuclear arylkyl and a 5- or 6-membered heterocycle]. When substituted, the substituents on the Y, Y' and Y" may be selected from halo, cyano, (C1-C5)alkyl, (C1-C5)alkoxy, (C2-C5) alkanoyl, (C,- C5) alkylthio, (C1-C5) alkylsulfinyl, (C1-C5) alkylsulfonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxy, halophenoxy, benzyloxy, trifluoromethyl and alkoxycarbonyl having up to 5 carbon atoms in the alkoxy group. [The invention also provides pharmaceutically or agronomically acceptable acid addition salts and amide derivatives of a compound of Formula I such as salts formed with hydrochloric, sulfuric, nitric, phosphoric, acetic, citric, benzoic or lactic acid or amides wherein the -OR' group in Formula I is replaced with amino, mono- or di-(C1-C5) alkylamino. [Representative R2 radicals include chlorophenyl, bromophenyl, methylphenyl, ethylphenyl, butylphenyl, pentylphenyl; 2,6-dichlorophenyl; 3,4-dichlorophenyl; methoxyphenyl, ethoxyphenyl, dimethylaminophenyl, acetamido; 3,4-methylenedioxyphenyl, methylthiophenyl and phenylthio-phenyl.

[In the compounds of Formula I examples of aromatic substituents include phenyl, naphthyl, thienyl, pyridyl, furyl, furylmethyl, pyrrolidinyl, pyrrolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, imidazolyl, isooxazolyl, N-methylpyrryl, oxazolyl and pyrimidyl, which may be unsubstituted or substituted with from 1 to 3 radicals selected from halo, (C1-C5) alkyl, (C1-CE) alkoxy di-lower alkylamino, (e.g. as dimethylamino) alkanoylamino of from 1 to 5 carbon atoms; phenoxy, benzyloxy, 3,4-alkylenedioxyphenyl having up to 5 carbon atoms in the alkylene group, phenythio (C1-C5) alkyl, cyano, nitro, alkylthio and arylthio.

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.

One embodiment of this invention concerns compounds of Formula Ia below (as well as the addition salts and amide derivatives thereof).

wherein R3 is (C1-C8) alkyl, (C3-Ca) alkenyl, (C,-C8) alkynyl, benzyl, 2,6 dichlorobenzyl, phenethyl, cycloalkyl (C1-C6) alkyl of from 5 to 6 nuclear atoms, phenoxy (C3-C6) alkyl, cyano (C3-C6) alkyl, alkoxy carbonyl alkyl having from 3 to 6 carbon atoms in each of the alkoxy and alkyl groups, phthalimido (D1-C6) alkyl, phenyl (C3-C6) alkenyl or hydroxy (C3-C8) alkyl; R4 is (C1-C6) alkyl; R5 is optionally substituted aryl of up to 14 nuclear carbon atoms or heteroaryl having 5 or 6 nuclear atoms containing from 1 to 3 hetero atoms selected from oxygen, nitrogen and sulfur, and X1 is in the 4 or 5 position of the benzene ring and is selected from hydrogen, (C1-C4) alkyl carbonylamino, (C1-C4) alkoxycarbonylamino, (C1-C5) alkoxy, (C2-C5) alkanoyl, propylthio, propylsulfinyl, propylsulfonyl, propylsulfonyloxy, propoxysulfonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy or benzoyl. Especially preferred are those compounds wherem X' is hydrogen, 4-benzoyl, 5-propylthio or 5-phenylthio; these compounds exhibit particularly good anthelmintic and antifungal activity.

Examples of R5 are o, m, orp-nitrophenyl, o, m orp-dimethylaminophenyl, o, m, or p-(C1-C5) alkoxyphenyl, o, m or p-cyanophenyl, o, m or p-acetamidophenyl, methylenedioxyphenyl, phenyl, 2-furyl, 5-methyl-2-furyl, 2-thienyl, o-, m, or p halophenyl, o, m, n or o-(C1-C5) alkyl phenyl and dihalophenyl.

Another embodiment of this invention concerns compounds of Formula I (and acid addition salts and amide derivatives) wherein: R is (C1-C8)alkyl, (C3-C8)alkenyl, (C3-C8)alkynyl, polynuclear aralkyl containing 2 to 3 alkyl carbon atoms, mononuclear aralkyl containing up to 3 alkyl carbon atoms and which may be optionally substituted with up to 3 of the same or different substituents selected from halo, alkyl, alkoxy, nitro and cyano, mononuclear aryloxy(C3-C6) alkyl, cycloalkylalkyl containing 5 or 6 cyclic carbon atoms and 1 to 2 alkyl carbon atoms, (C1-C8)alkoxy(C1-C8)alkyl, (C1-C6) (C1 C6)alkoxycarbonyl(C3-C6)alkyl, phthalimido(C1-C8)alkyl or phenoxycarbonyl(C3-C6)alkyl; R' is (C1-C6)alkyl, cyclopentyl, cyclohexyl or alkoxyalkyl of up to 8 carbon atoms; R is (C1-C6)alkyl, phenyl, naphthyl, thienyl, pyridyl each optionally substituted with up to 3 of the same or different substituents selected from halo, (C1-C5)alkyl, (C1-C5)alkoxy, di(C1-C8alkyl)amino, (C2-C5)alkanoylamino, phenoxy, benzyloxy, methylenedioxy, phenylthio (C1-C8)alkyl, cyano, nitro, (C1-C8)alkylthio and arylthio and X is (1) hydrogen, (2) nitro, (3) halo, (4) (C1-C5)alkoxy, (5) (C2-C5)alkanoyl, (6) (C1-C4)alkyl, (7) thiocyanato, (8) a group of the formula: Y(SOn) wherein Y is (C1-C5)alkyl, (C3-C6)alkenyl, (C3-C6)alkynyl, (C3-C7)cycloalkyl, phenyl, pyridyl, thienyl, furyl, pyrimidyl or thiazolyl and n is 0 or an integer of 1 to 3, (9) (C2-C8)alkylcarbonylamino, (10) alkoxycarbonylamino containing 2 to 5 carbon atoms, (I I) cycloalkylcarbonylamino containing 5 or 6 carbon atoms in the ring, (12) a group of the formula:

wherein Y' is phenyl, (C-C7)cycloalkyl, pyridyl, 2-thienyl or furyl or (13) a group of the formula Y"O wherein Y" is (C1-C5)alkyl, (C3-C6alkenyl, phenyl or benzyl, the Y, Y' and Y" groups as defined above being optionally substituted.

A yet further embodiment of the invention concerns compounds of Formula I (and acid addition salts and amide derivatives) wherein: R is (C1-C4)alkyl, aryl (C1-C4)alkyl, (C3-C8)alkenyl or 2,6-dichlorophenyl; R' is (C1-C4)alkyl; and R2 is phenyl or naphthyl optionally substituted with up to 3 of the same or different substituents selected from halo, nitro, (C,--C,)alkyl, (C1-C5)alkoxy, di(C,-C,)alkylamino; furyl or thienyl; and X is benzoyl, phenylthio, phenylsulfonyl, (C1-C5)alkylthio, (C1- C5)alkylsulfinyl, (C,-C,)alkylsulfonyl or hydrogen.

The novel compounds may be prepared by several alternative 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 substituted isothioureidobenzenes (I, supra) of this invention comprises treating the corresponding 2-imino substituted thioureidobenzene (II, infra) with a base, for example, an alkali metal or alkaline earth metal base, such as sodium hydride, calcium hydride, sodium hydroxide, potassium hydroxide, calcium hydroxide or potassium carbonate and the like followed by treatment with either an organic halide, a diester of sulfuric acid or diester of sulfurous acid. The reaction may be conducted at a temperature in the range of from -10"C to about 60"C for a period of time of from a few minutes to about 24 hours. Any solvent in which the reactants are reasonable soluble and substantially inert may be employed. Suitable solvents include dimethylformamide, acetone, 1 ,2-dimethoxyethane or dimethyl sulfoxide. The following equation illustrates this process:

x -ftORSO - Oi or RS04R - 0 I OR1 :NEOR1 SR II I wherein R, R' and R2 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 isothioureidobenzene with an aldehyde (R2CHO) in a manner similar to that described below for the preparation of the compounds of Formula III. The following equation illustrates this process:

wherein R, R', R2 and X are as defined above. It should be noted that compounds of Formula IIa are claimed in our copending Application No. 18212/77 (Serial No.

1,576,633). The compounds of Formula II are either known compounds or may be prepared by treating an appropriately substituted l-imino-2-aminobenzene (III, infra) with a carboalkoxyisotbiocyanate (IV, infra), to afford the desired compounds of Formula II. The following equation illustrates this process:

wherein R', R2 and X are as defined above. This reaction is conveniently conducted in a suitable inert solvent such as diethyl ether or acetone, for a period of time of from 30 minutes to 6 hours.

We have found that the compounds of Formula II, supra, which have been disclosed as anthelmintics are also useful as fungicides.

Compound IIa is prepared by the reaction of a thioureidobenzene (V, infra) (where Z' is

with RX2, RS03R or RS04R under the same conditions as described in the preparation of Formula I from Formula II.

The compounds of Formula II and also the compounds of Formula IIIa, 1 substituted - imino - 2 - substituted aminobenzene, may be prepared by treating the correspondingly substituted isothioureidobenzene or substituted 1,2diaminobenzene (V, infra), respectively, with an aldehyde. The following equation illustrates this process:

wherein R2 and X are as defined above and Z' is hydrogen or

wherein R' is as defined above. This reaction is generally conducted at a temperature in the range of from about 0 C to about 11"C for a period of time of from one minute to about 24 hours. Suitable solvents which can be employed include acetone, methanol, ethanol, iso-propanol, dimethylformamide or dimethyl sulfoxide. An acid catalyst such as p-toluene sulfonic acid or sulfuric acid may be employed. Any water formed during the reaction may be removed by azeotropic distillation.

When X is the radical YS, the sulfinyl (i.e., Y-SO-) and the sulfonyl product can be prepared by treating said YS substituted compound with one or two equivalents of an oxidizing agent, respectively. The oxidizing agent may be mchloroperbenzoic acid, perbenzoic acid, peracetic acid or sodium hypochlorite.

The reaction is conducted at a temperature in the range of from -20"C to 500C for a period of time of from about 5 minutes to 24 hours. Any substantially inert solvent in which the reactants are reasonably soluble may be employed including methylene dichloride, chloroform, carbon tetrachloride, benzene, toluene, chlorobenzene or acetone.

The thioureidobenzene of Formula V (where Z' is

is prepared by treating a 1 ,2-diaminobenzene derivative or 1 - amino - 2 nitrobenzene derivative with a carboalkoxy isothiocyanate in the manner described above and when a nitrobenzene reducing said nitro to an amino group by reduction methods well-known to those skilled in the art.

2-Imino substituted isothioureidobenzenes of Formula I are anthelmintics and have broad spectrum activity against parasites of animals, especially warm blooded animals, including both mature and immature parasitic forms. In particular, these compounds exhibit high activity against various helmintic infections of the intestinal tract of economically important animals, coupled with low systemic toxicity to the host animal.

For example, the disclosed compounds are generally effective in clearing mice of worm infections, for laboratory purposes, including: Syphacia obvelata and Aspicularis tetraptera, the migratory stages of Ascaris suum, Hymenolepsis nana and Nematoseiroides dubius.

Compounds of Formula I have been demonstrated as efficacious against gastrointestinal parasites in sheep, such as Moniezia spp, Haemonchus contortus.

Ostertagia spp, Trichostrangylus spp, Nematodirus spp, Trichuris ovis, Coaperia spp, Capillaria spp, Strongyloids papillosus, Bunostomum trigoncephalum and Oesophagostomum spp. The compounds are active against lung worms in ruminants especially Dictyocaulus aria, in sheep and Dictyocaulus viviparus and in cattle. The compounds (I) may also be used in treating Fasciola gigantica in cattle. In addition, the compounds are effective against liver flukes (Fasciola hepatica) in sheep and cattle.

Animals of low weight are treated with unit doses ranging no higher than a few milligrams; whereas, animals of high body weight, such as ruminants, require proportionately larger unit doses ranging up to several grams. Preferably, a single dose is administered for each animal species based on the weight of that species.

The amount of 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 this invention as the essential active ingredient will be administered, orally or by injection, in the treatment and control of helmintic infections in man and domestic animals such as sheep, cattle, horses, dogs, cats; fish, swine and goats.

Further applicants have found that the compounds of Formula I and Formula II display broad spectrum antifungal activity. It is contemplated, therefore, that antifungal compositions containing these compounds as an essential active ingredient will be employed in controlling the growth of fungi in or on animals and plants as well as in the paint, wood, textile, cosmetic, leather, tobacco, fur, rope, paper, pulp, plastic, fuel, rubber and food industries.

When used as an anthelmintic agent for the treatment and/or prevention of helminthiasis, the novel compounds of Formula I of this invention may be administered orally, rectally, intranasally, sublingually or topically, in a unit dosage form such as a capsule, bolus, tablet, suppository, paste, gel, spray, powder, ointment, cream or as a liquid drench. They may also be administered orally by intimately dispersing them in an animal feedstuff or by using them as a top dressing or in the form of pellets which are added to a finished feed. Alternatively, they may be administered to animals in a liquid carrier vehicle by intraruminal, interamuscular and intratracheal injection. In addition, polymeric implants providing a controlled release rate can be employed for administration. The quantity of active material required to give the best anthelmintic response will depend upon the particular compound employed, the species of animal to be treated and the type and severity of helminth infection. Good results are usually obtained when there is administered a total dose of from about 5 to about 125 mg of active ingredient per kg of animal body weight. Such total dose may be given at one time or in divided doses over a short period 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 soil or seed on the foliage af plants, particularly those yielding a vendible crop. 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 formulated to render them suitable for use as fungicides. For example, the compounds can be formulated as wettable powders, emulsifiable concentrates, dusts, granular formulations, aerosols, 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 environmentally acceptable.

It is usually desirable, particularly in the case of foliar spray formulations, to include adjuvants, such as wetting agents, spreading agents, dispersing agents, stickers or adhesives in accordance with the agricultural practices. Such adjuvants commonly used in the art can be found in the John W. McCutcheon, Inc. publication "Detergents and Emulsifiers, Annual".

In general, the compounds of this invention can be dissolved in organic solvents such as acetone, methanol, ethanol, dimethylformamide, pyridine or dimethyl sulfoxide and the resulting solutions can be extended with water. The concentrations of the solution can vary from about 1% to about 90% by weight with a preferred range being from about 5% to about 50%.

For the preparation of emulsifiable concentrates, the compound can be dissolved in suitable organic solvents, or a mixture of solvents, together 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 10% to about 90% by weight and in flowable emulsion concentrates, can be as high as about 75%.

Wettable powders suitable for spraying, can be prepared by admixing 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% by weight, preferably from about 40% to about 75%. A typical wettable powder is made by blending 50 parts of - - imino(2 - furylmethyl) - 2 - (3 - carbomethoxy - S - butylisothioureido)benzene, 45 parts of a synthetic precipitated hydrated silicon dioxide sold under the trademark Hi-Sil, and 5 parts of sodium lignosulfonate. In another preparation a kaolin type (Barden) clay is used in place of the Hi-Sil wettable powder, and in other preparation 25% by weight of the Hi-Sil is replaced with a synthetic sodium silico aluminat.e sold under the trademark Zeolex 7.

Dusts are prepared by mixing the compounds with finely divided inert 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 80% by weight of the active ingredient are commonly made and are subsequently diluted to from about 1% to about 10% use concentration.

The compounds of this invention can be applied as fungicidal sprays by methods commonly employed, such as conventional high-gallonage 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 application and diseases to be controlled, but the preferred effective amount is usually from about 0.1 lb to about 50 Ibs per acre of the active ingredient.

As a seed protectant, the amount of fungicide coated on the seed is usually at a dosage rate of from about 0.1 to about 20 ounces per hundred pounds of seed. As a soil fungicide the compound can be incorporated in the soil or applied to the surface usually at a rate of from about 0.1 to about 50 Ibs per acre. As a foliar fungicide, the compound is usually applied to growing plants at a rate of from about 0.25 to about 10 Ibs per acre.

Fungicides which can be combined with the fungicides of this invention include: (a) dithiocarbamate and derivatives such as: ferric dimethyldithiocarbamate (ferbam), zinc dimethyldithiocarbamate (ziram), manganese ethylenebisdithiocarbamate (maneb) and its coordination product with zinc ion (mancozeb), zinc ethylenebisdithiocarbamate (zineb), zinc propylenebisdithiocarbamate (propineb), sodium methyldithiocarbamate (metham), tetramethylthiuram disulfide (thiram), the complex of zineb and polyethylene thiuram disulfide, 3,5 - dimethyl - 1,3,5 - 2H tetrahydrothiadiazine - 2 - thione (dazomet); and mixtures of these and mixtures with copper salts; (b) nitrophenol derivatives such as: dinitro - ( I - methylheptyl)phenyl crotonate (dinocap), 2 - sec - butyl - 4,6 - dinitrophenyl - 3,3 - dimethylacrylate (binapacryl), and 2 - sec - butyl - 4,6 - dinitrophenylisopropyl carbonate; (c) Heterocyclic compounds such as N trichloromethylthiotetrahydrophthalimide (captan), N trichloromethylthiophthalimide (folpet), 2 - heptadecyl - 2 - imidazole acetate (glyodine), 2 - octylisothiazol - 3 - one, 2,4 - dichloro - 6 - (o - chloroanilino) s-triazine, diethyl phthalimidophosphorothioate, 4 - butyl - 1,2,4 - triazole - 5 amino - I - [bis(dimethylamino) - phosphinyll - 3 - phenyl - 1,2,4 - triazole, 5 ethoxy - 3 - trichloromethyl- 1,2,4 - triadiazole, 2,3 - dicyano - 1,4 dithiaanthraquinone (dithianon), 2 - thio - 1,3 - dithio - [4,5-b]quinoxaline (thioquinox), methyl 1 - (butylcarbamoyl) - 2- benzimidazole carbamate (benomyl, 2 - (4' - thiazolyl)benzimidazole (thiabendazole), 4- (2 chlorophenylhydrazone) - 3 - methyl - 5 - isoxazolone, pyridine - 2 - thio - I - oxide, 8 - hydroxyquinoline sulfate and metal salts thereof; 2,3 - dihydro - 5 carboxanilido - 6 - methyl - 1,4 - oxathiin - 4,4 - dioxide - 2,3 - dihydro - 5 carboxanili - do - 6 - methyl - 1,4 - oxathin, a - (phenyl) - a - (2,4 dichlorophenyl)- 5 - pyrimidinyl - methanol (triarimol), cis - N - [(1,1,2,2 - tetrachloroethyl)thiol - 4 - cyclohexene - 1,2 - dicarboxyimide, 3 - [2 - (3,5 - dimethyl - 2 - oxycyclohexyl - 2 - hydroxy] - glutarimide (cycloheximide), dehydroacetic acid, N - (1,1,2,2 - tetrachloroethylthio) - 3a,4,7,7a tetrahydrophthalimide (captafol), 5 - butyl - 2 - ethylamino - 4 - hydroxy - 6 methylpyrimidine (ethirimol), acetate of 4- cyclododecyl - 2,6 dimethylmorpholine (dodemorph), and 6 - methyl - 2 - oxo - 1,3 - dithiolo - [4,5- bi - quinoxaline (quinomethionate).

(d) miscellaneous halogenated fungicides such as tetrachloro- pbenzoqui 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.

EXAMPLE 1 3-Iminophenylmethyl-4-(3-carbomethoxy-S methylisothioureido)benzophenone Step A-3 - Iminophenylmethyl - 4 - aminobenzophenone To a solution of 3,4 - diaminobenzophenone (4.24 g; 0.02 mole) in methanol (50 ml) cooled to OOC is added benzaldehyde (2.12 g; 0.02 mole). The solution is stirred at 0 C for one hour. The precipitate is collected by filtration and dried to yield 3.0 g of 3 - iminophenylmethyl - 4 - aminobenzophenone, m.p. 112"-- 116"C.

Elemental analysis for C20Ht6N2O Calc.: C, 79.97; H, 5.37; N, 9.33 Found: C,80.11; H,5.57; N,9.28 Step B-3 - Iminophenylmethyl - 4- (3 - carbomethoxythioureido) benzophenone To a solution of 3 - iminophenylmethyl - 4 - aminobenzophenone (0.5 g; 0.00166 mole) in diethylether (100 ml) is added carbomethoxy isothiocyanate (0.19 g; 0.00166 mole). The solution is stirred at room temperature for three hours. The precipitate is collected by filtration and dried to yield 0.35 g of 3 iminophenylmethyl- 4 - (3 - carbomethoxythioureido)benzophenone, m.p. l940-l950C (dec).

Elemental analysis for C23H1gN3O3S Calc.: C, 66.17; H;4.59; N, 10.07 Found: C, 65.81; H, 4.53; N, 9.80 Step C-3 - Iminophenylmethyl - 4 - (3 - carbomethoxy - S methylisothioureido)benzophenone To a solution of 3 - iminophenylmethyl - 4 - (3 carbomcthoxythioureido)benzophenone (1.1 g; 0.0026 mole) in dimethylformamide (10.0 ml) is added water (3.0 ml). Additional dimethylformamide (25.0 ml) is added to dissolve some precipitate and then sodium hydroxide (50% aqueous; 0.21 g; 0.0026 mole) is added. The resulting solution is stirred at room temperature for 16 hours and then methyl iodide (0.38 g; 0.0026 mole) is added. The solution is stirred for one hour at room temperature and then poured into water (250 ml). The precipitate is collected by filtration and dried to afford 0.95 g of 3- iminophenylmethyl- 4- (3- carbomethoxy - S methylisothioureido)benzophenone, m.p. 1400-l420C (dec).

Elemental analysis for C24H2,N303S Calc.: C, 66.80; H, 4.91; N, 9.74 Found: C,65.68; H,4.86; N, 10.44 EXAMPLE 2 3-Iminophenylmethyl-4-(3-carbomethoxy-S methylisothioureido)benzophenone To a suspension of 3 - iminophenylmethyl - 4 - (3 carbomethoxythioureido)benzophenone (2.09 g; 0.005 mole) in a mixture of acetone (20 ml) and water (3.0 ml) is added aqueous sodium hydroxide solution (50%; 0.4 g). The mixture is stirred for one hour at room temperature. To the solution is added methyl iodide (0.71 g; 0.005 mole). Within two minutes a thick suspension forms. Additional acetone (20 ml) and water (3.0 ml) is added and stirring is continued for 18 hours. The precipitate is collected by filtration and dried to afford 2.05 g of 3 - iminophenylmethyl- 4- (3 - carbomethoxy - S methylisothiouredio)benzophenone, m.p. 157"--158"C (dec).

Elemental analysis for C24H2,N303S Calc.: C,66.80; H,4.91; N,9.74 Found: C,66.31; H,4.83; N,9.95 EXAMPLE 3 2-Imino(2,6-dichloro)phenylmethyl-4-(3-carbomethoxy- S-methylisothioureido)benzophenone Step A-2 - Imino - (2,6 - dichloro)phenylmethyl - 4 - aminobenzophenone To an ice cooled solution of 3,4-diaminobenzophenone (8.48 g; 0.04 mole) in methanol (100 ml) is added a solution of 2,6 - dichlorobenzaldehyde (7.06 g; 0.04 mole) in methanol (100 ml). The solution is stirred at 0 C for one hour and at room temperature over the weekend. The precipitate formed is collected by filtration and dried to afford 11.5 g of 2 - imino - (2,6 - dichloro)phenylmethyl - 4 aminobenzophenone, m.p. 141 0-1440C.

Step B-3 - Imino(2,6 - dichloro)phenylmethyl - 4 - (3 carboxymethoxythioureido)benzophenone To a solution of 2 - imino - (2,6 - dichloro) - phenylmethyl - 4 aminobenzophenone (2.08 g; 0.005 mole) in diethyl ether (600 ml) is added carbomethoxy isothiocyanate (0.88 g; 0.0075 mole). The solution is stirred at room temperature for 18 hours. The precipitate which forms is collected and dried to yield 1.8 g of 3 - imino(2,6 - dichloro)phenylmethyl - 4 - (3 carboxymethoxythioureido)benzophenone, m.p. 197 C (dec.) Elemental analysis for C2317Cl2N3O3S Calc.: C, 56.79; H, 3.52; N,8.64 Found: C, 57.49; H, 3.66; N, 8.84 Step C-3 - Iminophenylmethyl - 4 - (3 - carboxymethoxy - S - methyl isothioureido)benzophenone To a solution of 3- imino(2,6- dichloro)phenylmethyl - 4- (3carbomethoxythioureido)benzophenone (2.43 g; 0.005 mole) in dimethylformamide (100 ml) is added water (5.0 ml) and then sodium hydroxide (50% aqueous; 0.4 g; 0.005 mole). The solution is stirred for 1 hours and then methyl iodide (0.71 g; 0.005 mole) is added. The solution is stirred for one-half hour. The precipitate which forms is collected by filtration and dried to afford 1.3 g of 3 - iminophenylmethyl - 4 - (3 - carboxymethoxy - S - methylisothioureido)benzophenone, m.p. 63 -68 C (dec.) Elemental analysis for C24H19C12N3O3S Calc.: C, 57.60; H, 3.83; N, 8.40; S, 6.41 Found: C, 56.65; H,3.80; N, 8.48; S, 5.84 EXAMPLE 4 3-Imino-(4-methylphenyl)methyl-4-(3 -carbomethoxy S-methylisothioureido)benzophenone Step A-3 - Imino - (4 - methylphenyl)methyl - 4 - aminobenzophenone To an ice cooled solution of 3,4-diaminobenzophenone (6.36; 0.03 mole) in methanol (75 ml) is added p-tolualdehyde (3.6 g; 0.03 mole). The solution is stirred at 5 C 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 - (4 methyl)phenylmethyl - 4 - aminobenzophenone, m.p. 136 -137 C.

Step B-3 - Imino - (4 - methylphenyl)methyl - 4 - (3 carbomethoxythioureido)benzophenone To a solution of 3 - imino - (4 - methylphenyl)methyl - 4 aminobenzophenone (4.5 g; 0.0145 mole) in dimethoxyethane (75 ml) and diethyl ether (25 ml) is added carbomethoxy isothiocyanate (1.68 g; 0.0145 mole). The solution is stirred at room temperature for 10 minutes at which time a precipitate begins to form. Stirring is continued at room temperature for one hour and the precipitate is collected by filtration and dried to afford 3.9 g of 3 - imino - (4 methylphenyl)methyl - 4 - (3 - carbomethoxythioureido)benzophenone, m.p.

20l0-2020C (dec).

Elemental analysis for C24H2,N303S Calc.: C, 66.80; H, 4.91; N, 9.74 Found: C, 66.73; H, 4.79; N, 10.18 Step C-3 - Imino - (4 - methylphenyl)methyl - 4 - (3 - carbomethoxy - S methylisothioureido)benzophenone To s solution of 3 - imino - (4 - methylphenyl)methyl - 4 - (3 carboxymethoxythioureido)benzophenone (2.0 g; 0.00463 mole) in dimethylformamide (100 ml) and 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 - (4 methylphenyl)methyl - 4 - (3 - carbomethoxy - S- methylisothioureido)benzophenone, m.p. 40"--45"C (dec).

Elemental analysis for C25H23N3O3S Calc.: C, 67.39; H, 5.20; N, 9.43; S, 7.20 Found: C, 66.81; H, 5.22; N, 9.94; S, 7.23 EXAMPLE 5 3-Imino-(4-chlorophenyl)methyl-4-(3-carbomethoxy S-methylisothioureido)benzophenone Step A-3 - Imino(4 - chlorophenyl)methyl - 4 - aminobenzophenone To an ice cooled solution of 3,4-diaminobenzophenone (8.4 g; 0.04 mole) in methanol (100 ml) is addedp-chlorobenzaldehyde (5.6 g; 0.04 mole). The solution is stirred at 00--50C for one hour and at room temperature for 18 hours. The precipitate which forms is collected and dried to afford 9.2 g of 3 - imino - (4 chlorophenyl)methyl - 4 - aminobenzophenone, m.p. 1230-l250C.

Elemental analysis for C20H1 5ClN2O Calc.: C, 71.74; H, 4.52; H, 8.37 Found: C, 71.87; H, 4.43; N, 8.60 Step B-3 - Imino - (4 - chlorophenyl)methyl - 4 - (3 carbomethoxythioureido)benzophenone To a solution of 3 - imino - (4- chloro) - phenylmethyl - 4aminobenzophenone (7.9 g; 0.02 mole) in diethyl ether (700 ml) is added carbomethoxy isothiocyanate (2.34 g; 0.02 mole). The solution is stirred at room temperature for 18 hours. The precipitate which forms is collected by filtration and dried to afford 6.6 g of 3 - imino - (4 - chloro)phenylmethyl - 4- (3 carbomethoxythioureido)benzophenone, m.p. 2120--216"C (dec).

Elemental analysis for C23H,8CIN303S Calc.: C, 61.12; H, 4.01; N, 9.30 Found: C, 61.37; H, 4.06; N, 9.72 Step C-3 - Imino - (4 - chlorophenyl)methyl - 4 - (3 - carbomethoxy - S methylisothioureido)benzophenone To a solution of 3- imino - (4- chlorophenyl)methyl - 4- (3- carbomethoxythioureido)benzophenone (4.52 g; 0.01 mole) in dimethylformamide (200 ml) and water (5.0 ml) is added aqueous sodium hydroxide (50% aqueous; 0.8 g). The solution is stirred at room temperature for one hour and then methyl iodide (1.42 g; 0.01 mole) is added. The solution is stirred at room temperature for 25 minutes and then poured into water (700 ml). The suspension which forms is then stirred for 5 minutes and the precipitate is collected by filtration and dried to afford 4.3 g of 3 - imino - (4 - chlorophenyl)metbyl - 4 - (3 - carbomethoxy - S methylisothioureido)benzophenone, m.p. 156"--157"C (dec).

Elemental analysis for C24H20C1N3O3S Calc.: C, 61.86; H, 4.33; N, 9.02 Found: C, 60.97; H, 4.21; N, 9.51 EXAMPLE 6 3-Iminophenylmethyl-4-(3-carbomethoxy-S benzylisothioureido)benzophenone To a solution of 3 - iminophenylmethyl - 4 - (3 - carbomethoxythioureido)benzophenone (2.35 g; 0.0054 mole) in dimethylformamide (100 ml) and water (10 ml) there is added aqueous sodium hydroxide solution (50%; 0.44 g). The solution is stirred at room temperature for one hour and then benzyl bromide (0.93 g; 0.0054 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 afford 2.45 g of 3 - iminophenylmethyl - 4 - (3 - carbomethoxy - S benzylisothioureido)benzophenone, m.p. 500--700C (dec).

Elemental analysis for C30H25N3O3S Calc.: C, 70.98; H, 4.96; N, 8.28 Found: C, 69.44; H, 4.98; N, 8.90 EXAMPLE 7 3-Iminophenylmethyl-4-(3-carbomethoxy-S allylisothioureido)benzophenone To a suspension of 3 - iminophenylmethyl - 4 - (3 carbomethoxythioureido)benzophenone (2.09 g; 0.005 mole) in acetone (40 ml) and water (6.0 ml) is added an aqueous sodium hydroxide solution (50% aqueous; 0.4 g).

The suspension is stirred at room tmeperature for one hour and then allyl bromide (0.6 g; 0.005 mole) is added and the solution is stirred at room temperature over the weekend. The precipitate which forms is collected by filtration and then dried to afford 1.3 g of 3 - iminophenylmethyl)- 4- (3 - carboxymethoxy - S allylisothioureido)benzophenone, m.p. 125 -127 C.

Elemental analysis for C26H23N3O3S Calc.: C, 68.25: H, 5.07; N, 9.18 Found: C, 67.93; H, 4.98; N, 8.79 EXAMPLE 8 1 -(3-Carbomethoxy-S-methylisothioureido)-2 iminophenylmethyl-5-propylthiobenzene Step A-1 - (3 - Carbomethoxythioureido) - 2 - nitro - 5 - propylthiobenzene To a stirred mixture of 2 - nitro - 5 - propylthioaniline (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 to 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 1 (3 - carbomethoxythioureido) - 2 - nitro - 5 - propylthiobenzene (17.9 g), m.p.

1220--125"C.

Step B-l - (3 - Carbomethoxythioureido) - 2 - amino - 5 - propylthiobenzene A mixture of 1-(3- carbomethoxythioureido) - 2- nitro - 5propylthiobenzene (4.4 g; 0.0134 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 dichloromethane and the dichloromethane removed to afford 3.8 g of 1 - (3 - carbomethoxythioureido) - 2 - amino - 5 - propylthiobenzene.

Step C-I - (3 - Carbomethoxythioureido) - 2- iminophenylmethyl- 5 propylthiobenzene To an ice-cooled solution of 1 - (3 - carbomethoxythioureido) - 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 50C for an hour and the precipitate which forms is collected by filtration and dried to afford 0.6 g of 1 (3 - carbomethoxythioureido) - 2 - iminophenylmethyl - 5 - propylthiobenzene, m.p. 1090-ll00C.

Elemental analysis for C19H21N3O2S2 Calc.: C, 58.89; H, 5.46; N, 10.84 Found: C,58.85; H, 5.46; N,11.02 Step D-l - (3 - Carbomethoxy - S- methylisothioureido) - 2 iminophenylmethyl - 5 - propylthiobenzene To a solution of 1 - (3 - carbomethoxythioureido) - 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+ 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 (100 ml). The suspension formed is stirred at room temperature for 1+ hours and then the precipitate collected by filtration and dried to afford 0.35 g of - - (3 - carbomethoxy - S - methylisothioureido) - 2 - iminophenylmethyl - 5 - propylthiobenzene, m.p. 80"--83"C (dec).

Elemental analysis for C20H23N303S2 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 EXAMPLE 9 1 -(3-Carbomethoxy-S-methylisothioureido)-2 iminophenylmethyl-4-benzenesulfonylbenzene Step A-2 - Iminophenylmethyl - 4 - benzenesulfonylaniline To an ice-cooled solution of 2 - amino - 4 - benzenesulfonylaniline (5.2 g; 0.021 moie) in methanol (25 ml) is added benzaldehyde (2.23 g; 0.021 mole). The solution is stirred at OOC for 11 hours. A suspension forms which is stirred at room temperature overnight and then the precipitate collected by filtration is washed with methanol and then ether and then dried to afford 6.0 g of 2iminophenylmethyl - 4 - benzenesulfonylaniline, m.p. l590-l600C.

Elemental analysis for C19H16N2O2S Calc.: C, 67.83; H, 4.79; N, 8.33 Found: C, 67.54; H, 4.90; N, 8.62 Step B-I - (3 - Carbomethoxythioureido) - 2- iminophenylmethyl- 4 benzenesulfonylbenzene To a solution of 2 - iminophenylmethyl - 4 - benzenesulfonylaniline (4.5 g; 0.0134 mole) in acetone (250 ml) is added carbomethoxy isothiocyanate (1.57 g; 0.0134 mole). The solution is stirred at room temperature for two hours and the precipitate which forms is collected by filtration, washed with ether and dried to afford 2.15 g of 1 - (3 - carbomethoxythioureido) - 2 - iminophenylmethyl - 4 benzenesulfonylbenzene, m.p. 207"--208"C (dec).

Elemental analysis for C22H1gN304S2 Calc.: C, 58.26; H, 4.22; N, 9.27 Found: C, 58.32; H, 4.14; N, 9.40 Step C-i - (3 - Carbomethoxy - S - methylisothioureido) - 2 iminophenylmethyl - 4 --benzenesulfonylbenzene To a suspension of 1 - (3 - carbomethoxythioureido) - 2iminophenylmethyl - 4 - benzenesulfonylbenzene (1.0 g; 0.0022 mole) in acetone (10 ml) and water (1.0 my) there is added an aqueous sodium hydroxide solution (50%; 0.18 g). This mixture is stirred at room temperature for 2 hours and a fine suspension which forms is removed by filtration. To the filtrate is added methyl iodide (0.313 g; 0.0022 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 carbomethoxy - S- methylisothioureido) - 2- iminophenylmethyl- 4benzenesulfonylbenzene.

Elemental analysis for C23H2,N304S2 Calc.: C, 59.08; H, 4.53; N, 8.99 Found: C, 58.67; H, 4.39; N, 8.79 EXAMPLE 10 3-Iminophenylmethyl-4-(3-carbomethoxy-S butylisothioureido)benzophenone To a suspension of 3 - iminophenylmethyl - 4 - (3 carbomethoxythioureido)benzophenone (3.12 g; 0.0075 mole) in acetone (60 ml) and water (10 ml) there is added an aqueous solution of sodium hydroxide (50%; 0.6 g). The mixture is stirred at room temperature for 11 hours and to the solution form there is added n-butyl iodide (1.38 g; 0.0075 mole). The solution is stirred at room temperature for 2 hours and the suspension which forms is collected by filtration, washed with ether and dried to afford 1.9 g of 3 - iminophenylmethyl - 4 - (3 carbomethoxy - S - n - butylisothioureido)benzophenone, m.p. 1050--1070C (dec).

Elemental analysis for C2,H27N303S Calc.: C, 68.47; H, 5.75; N, 8.87 Found: C, 67.56; H, 5.77; N, 8.52 EXAMPLE 11 3-Iminophenylmethyl-4-[3-carbomethoxy-S-(2,6- dichlorophenyl)isothioureido]benzophenone To a suspension of 3 - iminophenylmethyl- 4- (3 - carbomethoxythioureido)benzophenone (3.12 g; 0.0075 mole) in acetone (60 ml) and water (10 ml) is added an aqueous solution of sodium hydroxide (50%; 0.6 g). The mixture is stirred at room temperature for 2 hours and then (L- - bromo - 2,6 dichlorotoluene (1.3 g; 0.0075 mole) is added. This solution is stirred at room temperature for one half hour. The precipitate which forms is collected by filtration, washed with ester and dried to afford 2.5 g of 3 - iminophenylmethyl 4 - [3 - carboyethoxy - S - (2,6 - dichlorophenyl)isothioureido]benzophenone, m.p. 148 -150 C (dec).

Elemental analysis for C30H23Cl2N3O3S Calc.: C, 62.50; H, 4.02; N, 7.29 Found: C, 61.64; H,3.95; N, 7.21 EXAMPLE 12 3-(Imino-(4-nitrophenyl)methyl-4-(3-carbomethoxy S-methylisothioureido)benzophenone Step A-3 - Imino - (4 - nitrophenyl)methyl - 4 - aminobenzophenone To a solution of 3,4 - diaminobenzophenone (8.48 g; 0.04 mole) in methanol (100 ml) is added p-nitrobenzaldehyde (6.04 g; 0.04 mole). The reaction mixture is stirred for 5 days and the precipitate is collected by filtration and dried to afford 12.45 g of 3 - imino - (4 - nitrophenyl)methyl - 4 - aminobenzophenone, m.p.

16l0-l630C (dec).

Step B-3 - Imino - (4 - nitrophenylmethyl) - 4 - (3 - carbomethoxythioureido) benzophenone To a solution of 3 - imino - (4 - nitrophenylmethyl - 4 - aminobenzophenone (6.9 g; 0.02 mole) in acetone (225 ml) there is added carbomethoxy isothiocyanate (2.34 g; 0.02 mole). The solution is stirred at room temperature for 18 hours. The precipitate which forms is collected by filtration and then dried to afford 7.35 g of 3 - imino - (4 - nitrophenylmethyl) - 4 - (3 - carboxymethoxythioureido)benzo phenone, m.p. 229 -230 C (dec).

Step C-3 - Imino - (4 - nitrophenyl)methyl- 4- (3- carbomethoxy - S methylisothioureido)benzophenone To a suspension of 3 - imino - (4 - nitrophenylmethyl) - 4 - (3 carboxymethoxythioureido)benzophenone (4.62 g; 0.01 mole) in acetone (160 ml) and water (24 ml) there is added an aqueous solution of sodium hydroxide (50%; 0.8 g).

The solution is stirred at room temperature for one hour at which time methyl iodide (1.42 g; 0.01 mole) is added. The suspension forms and the reaction mixture is stirred for 30 minutes. The precipitate is collected by filtration, washed with ether and dried to afford 2.55 g of 3 - imino - (4 - nitrophenyl)methyl - 4 - (3 carbomethoxy - S - methylisothioureido)benzophenone, m.p. 1800-1820C (dec).

Elemental analysis for C24H20N4O5S Calc.: C,60.49; H,4.23; N, 11.76 Found: C, 60.90; H,4.33; N, 11.87 EXAMPLE 13 3-Imino-(2-naphthylmethyl)-4-(3-carbomethoxy S-methylisothioureido)benzophenone Step A-3 - Imino - (2 - naphthylmethyl) - 4 - aminobenzophenone To an ice cooled solution of 3,4-diaminobenzophenone (10.6 g; 0.05 mole) in methanol (120 ml) is added 2-naphthaldehyde (7.8 g; 0.05 mole). The solution is stirred at 50C for 2 hours at room temperature overnight. Sulfuric acid (5 drops) is added and the solution stirred an additional 5 days at room temperature. The precipitate is collected by filtration and dried to afford 5.25 g of 3 - imino - (4 nitrophenyl)methyl - 4 - aminobenzophenone, m.p. 141 0-1430C (dec).

Elemental analysis for C24H'8N2O Calc.: C, 82.26; H, 5.18; N, 8.00 Found: C,81.53; H,4.98; N, 7.19 Step B-3 - Imino - (2 - naphthylmethyl) - 4 - (3 carbomethoxythioureido)benzophenone To a solution of 3 - imino - (2 - naphthyl) - 4 - (aminobenzophenone) (4.0 g; 0.0114 mole) in acetone (50 ml) is added carbomethoxy isothiocyanate (1.34 g; 0.0114 mole). A suspension forms within 5 minutes and stirring is continued at room temperature for 18 hours. The precipitate is collected by filtration, washed successively with acetone and ether and then dried to afford 3.1 g of 3 - imino (2 - naphthylmethyl) - 4 - (3 - carboxymethoxythioureido)benzophenone, m.p.

207-209 C (dec).

Elemental analysis for C27H21M3O3S Calc.: C, 69.36; H, 4.53; N, 8.99 Found: C, 69.37; H, 4.58; N, 8.83 Step C-3 - Imino - (2- napthylmethyl)- 4 - (3 - carbomethoxy - S methylisothioureido)benzophenone To a suspension of 3 - imino - (2- napthylmethyl)- 4- (3 carbomethoxythioureido)benzophenone (2.5 g; 0.0535 mole) in acetone (25 ml) and water (3 ml) there is added an aqueous sodium hydroxide solution (50%; 0.43 g).

The mixture is stirred at room temperature for 18 hours and then filtered. To the filtrate is added methyl iodide (0.76 g; 0.00535 mole). The precipitate forms within 5 minutes. The suspension is stirred at room temperature for 30 minutes and the precipitate is collected by filtration, washed with ether and dried to afford 0.8 g of 3 - imino - (2 - napthylmethyl) - 4- (3 - carbomethoxy - S methylisothioureido)benzophenone, m.p. 147 149.5 C (dec).

Elemental analysis for C28H23N3O3S Calc.: C, 69.83; H,4.81; N, 8.73 Found: C, 69.28; H, 4.82; N, 8.50 EXAMPLE 14 3-Imino-(4-methoxyphenylmethyl)-4-(3-carbomethoxy S-methylisothioureido)benzophenone Step A-3 - Imino - (4 - methoxyphenylmethyl) - 4 - aminobenzophenone To an ice-cooled solution of 3,4-diaminobenzophenone (10.6 g; 0.05 mole) in methanol (120 ml) is addedp-anisaldehyde (6.8 g; 0.05 mole). The solution is stirred at 50C for 2 hours and at room temperature for 18 hours. Sulfuric acid (5 drops) is added to the solution and it is stirred an additional 9 days at room temperature. The precipitate is collected by filtration, washed with ether and then dried to afford 4.2 g of 3 - amino - (4 - methoxyphenylmethyl) - 4 - aminobenzophenone, m.p.

129 131 C (dec).

Step B3 - Imino - (4 - methoxyphenylmethyl) - 4 - (3 carbomethoxythioureido)benzophenone To a solution of 3- imino - (4 - methoxyphenylmethyl) - 4aminobenzophenone (4.29 g; 0.0127 mole) in acetone (75 ml) is added carbomethoxy isothiocyanate (1.49 g; 0.027 mole). The solution is stirred at room temperature for 18 hours (a precipitate forms within 3 minutes). The precipitate is collected by filtration, washed with ether and then dried to afford 3.3 g of 3 imino - (4 - methoxyphenylmethyl) - 4- (3 - carbomethoxythioureido)benzophenone, m.p. 1820--1840 (dec).

Step C-3 - Imino - (4 - methoxyphenylmethyl) - 4 - (3 - carbomethoxy - S methylisothioureido)benzophenone To a suspension of 3 - imino - (4 - methoxyphenylmethyl) - 4- (3 carbomethoxythioureidobenzophenone (2.5 g; 0.0056 mole) in acetone (20 ml) and water (4 ml) there is added an aqueous solution of sodium hydroxide (50%; 0.45 g).

The reaction mixture is stirred at room temperature for two hours. A solid which forms is removed by filtration and to the clear filtrate is added methyl iodide (0.79 g; 0.0056 mole). A precipitate forms within 5 minutes. The suspension is stirred at room temperature for 30 minutes and the precipitate is collected by filtration, washed with ether and dried to afford. 1.1 g of 3 - imino - (4 methoxyphenylmethyl) - 4 - (3 - carbomethoxy - S methylisothioureido)benzophenone, m.p. 136"--138"C(dec).

Elemental analysis for C25H23N3O4S Calc.: C, 65.06; H, 5.02; N, 9.10 Found: C, 64.87; H, 5.04; N, 8.87 EXAMPLE 15 3-Imino-(2-nitrophenylmethyl)-4-(3-carbomethoxy S-methylisothioureido)benzophenone Step A-3 - Imino - (2 - nitrophenylmethyl) - 4 - aminobenzophenone To an ice-cooled solution of 3,4-diaminobenzophenone (8.48 g; 0.04 mole) in methanol (100 ml) there is added o-nitrobenzaldehyde (6.04 g; 0.04 mole). The mixture is stirred at 50C 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 for 18 hours and a precipitate collected by filtration, washed with ether and dried to afford 10.85 g of 3 - imino - (2 - nitrophenylmethyl) - 4 - aminobenzophenone, m.p. 1400--142"C (dec). This material is used in the next step without further purification.

Step B-3 - Imino - (2 - nitrophenylmethyl) - 4 - (3 - carbomethoxythioureido) benzophenone To a solution of 3 - imino - (2 - nitrophenylmethyl) - 4 aminobenzophenone (10.0 g; 0.029 mole) in acetone (100 ml) is added carbomethoxy isothiocyanate (3.4 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 - nitrophenylmethyl)- 4- (3 carbomethoxythioureido)benz one hour and then methyl iodide (0.88 g; 0.0062 mole) is added. The solution is stirred at room temperature for 20 minutes and then poured into water (1.0 1). The suspension is filtered to collect the precipitate and then dried to afford 2.55 g of 3 imino - (3,4 - dichlorophenylmethyl) - 4 - (3 - carboxymethoxy - S methylisothioureido)benzophenone, m.p. 168-174 C (dec).

Elemental analysis for C24H19Cl2N3O3S Calc.: C, 57.60; H, 3.83; N, 8.40 Found: C, 57.22; H, 3.79; N, 8.24 EXAMPLE 17 3-lmino-(2-chlorophenylmethyl)-4-(3-carbomethoxy- S-methylisothioureido)benzophenone Step A-3 - Imino - (2 - chlorophenylmethyl) - 4 - aminobenzophenone To an ice-cooled solution of 3,4-diaminobenzophenone (16.96 g; 0.08 mole) in methanol (200 ml) is added o-chlorobenzaldehyde (11.2 g; 0.08 mole). The solution is stirred at room temperature for 30 minutes and the precipitate which separates is collected by filtration and dried to afford 20.5 g of 3 - imino - (2 chlorophenylmethyl) - 4 - aminobenzophenone, m.p. 112 C (dec).

Step B-3 - Imino - (2 - chlorophenylmethyl) - 4 - (3 carbomethoxythioureido)benzophenone To a solution of 3 - imino - (2 - chlorophenylmethyl) - 4 aminobenzophenone (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. The 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) - 4 (3 - carbomethoxythioureido)benzophenone, m.p. 2040-2050C (dec).

Elemental analysis for C23H18ClN3O3S Calc.: C, 61.12; H, 4.01; N, 9.30 Found: C, 60.93; H, 4.00; N, 9.19 Step C-3 - Imino - (2 - chlorophenylmethyl) - 4 - (3 - carbomethoxy - S methyisothioureido)benzophenone To a suspension of 3- imino - (2 - chlorophenylmethyl) - 4- (3- carbomethoxythioureido)benzophenone (3.0 g; 0.0066 mole) in acetone (50 ml) and water (10 ml) is added an aqueous solution of sodium hydroxide (50%; 0.53 g). The mixture is stirred at room temperature for one hour and then methyl iodide (0.94 g; 0.0066 mole) is added. The solution is stirred at room temperature over the weekend and the precipitate which forms is collected by filtration and dried to afford 0.9 g of 3 - imino - (2 - chlorophenylmethyl) - 4 - (3 - carboxymethoxy - S methylisothioureido)benzophenone, m.p. 140-142 C (dec).

Elemental analysis for C24H20ClN3O3S Calc.: C, 61.86; H, 4.33; N, 9.02 Found: C, 61.76; H, 4.40; N, 8.80 EXAMPLE 18 3-Imino-(4-dimethylaminophenylmethyl)-4-(3-carbomethoxy- S-methylisothioureido)benzophenone Step A-3 - Imino - (4 - dimethylaminophenylmethyl) - 4 - aminobenzophenone To an ice-cooled solution of 3,4-diaminobenzophenone (8.48 g; 0.04 mole) in methanol (100 ml) is added p - N,N - dimethylaminobenzaldehyde (6.0 g; 0.04 mole). The mixture is stirred at 5 C for one hour and at room temperature for 18 hours. Sulfuric acid (3 drops) is added to the reaction mixture and within one hour a thick suspension forms. The reaction mixture is stirred at room temperature for an additional 8 hours and the precipitate is collected and dried to afford 10.2 g of 3 - imino - (4 - dimethylaminophenylmethyl) - 4- aminobenzophenone, m.p. l7l0-l730C (dec).

Elemental analysis for C22H21N3O Calc.: C. 76.94; H, 6.16; N, 12.24 Found: C, 76.08; H, 6.17; N, 12.03 Step B-3 - Imino - (4 - dimethylaminophenylmethyl) - 4- (3 carbomethoxythioureido)benzophenone To a solution of 3 - imino - (4 - dimethylaminophenylmethyl) - 4aminobenzophenone (9.6 g; 0.0262 mole) in acetone (2 1) there is added carbomethoxy isothiocyanate (3.0 g; 0.0262 mole). The solution is stirred at room temperature for 10 days and the acetone remove dunder vacuum. The residue is slurried in 100 ml of acetone and filtered and washed with ether and then dried to afford 8.0 g of 3 - imino - (4 - dimethylaminophenylmethyl) - 4- (3- carbomethoxythioureido)benzophenone, m.p. 199"C (dec).

Elemental analysis for C25H24N4O3S Calc.: C,65.20; H,5.25; N, 12.17 Found: C, 65.05; H, 5.25; N, 11.98 Step C-3 - Imino - (4 - dimethylaminophenylmethyl) - 4 - (3 - carbomethoxy S - methylisothioureido)benzophenone To a suspension of 3 - imino - (4 - dimethylaminophenylmethyl) - 4 - (3 carbomethoxythioureido)benzophenone (3.0 g; 0.0065 mole) in acetone (50 ml) and water (10 ml) there is added an aqueous solution of sodium hydroxide (50%; 0.52 g).

The mixture is stirred at room temperature for one hour and then methyl iodide (0.93 g) is added. The solution is stirred at room temperature for one hour (a precipitate begins to form after 15 minutes). The precipitate which forms is collected by filtration and dried to afford 0.6 g of 3- imino - (4 -' dimethylaminophenylmethyl) - 4 - (3 - carbomethoxy - S - methylisothioureido) benzo henone, m.p. 143"--1440C (dec).

Elemental analysis for C2zH21N3O Calc.: C,7694; H,6.16; N, 12.24 Found: C,76.08; H,6.17; N,12.03 EXAMPLE 19 1 -Imino-(p-chlorophenyl)methyl-2-(3-carbomethoxy- S-methylisothioureido)-4-propylthiobenzene Step A-l - Imino - (p - chlorophenyl)methyl - 2 - (3 carbomethoxythioureido) - 4 - propylthiobenzene To an ice-cooled solution of 1 - amino - 2 - (3 - carbomethoxythioureido) 4 - propylthiobenzene (3.0 g) in absolute methanol (100 ml) there is added finely divided p-chlorobenzaldehyde (1.4 g). The yellow solution formed is stirred at 50C for one hour (precipitate forms after 10 minutes). The precipitate is collected by filtration. The yellow solid is dried to afford 1.2 g of I - imino - (p chlorophenyl)methyl - 2 - (3 - carboxymethoxythioureido) - 4 - propylthiobenzene, m.p. 170 -172 C (dec).

Elemental analysis for C19H20ClN3O2S2 Calc.: C,54.08; H,4.78; N,9.96 Found: C, 54.04; H,4.80; N, 9.89 Step B-l - Imino - (p - chlorophenyl)methyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - propylthiobenzene To a suspension of 1 - imino - (p - chlorophenyl)methyl - 2 - (3 - carbomethoxyisothioureido) - 4 - propylthiobenzene (1.2 g) in acetone (30 ml) and water (10 ml) is added sodium 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 minutes. The precipitate is collected by filtration, washed with ether and dried to afford 1.05 g of 1 - imino - (p chlorophenyl)methyl - 2 - (3 - carboxymethoxy - S - methylisothioureido) - 4 propylthiobenzene, m.p. 1390--1400C.

Elemental analysis for C20H22ClN3O2S2 Calc.: C, 55.09; 11, 5.09; N, 9.64 Found: C, 54.28; H, 5.06; N, 9.29 EXAMPLE 20 1 -Imino-(2-thienyl)methyl-2-(3-carbomethoxy-S- methylisothioureido)-4-propylthiobenzene Step A-l - Imino - (2 - thienyl)methyl - 2 - (3 - carbomethoxythioureido) - 4 propylthiobenzene To an ice-cooled solution of 1 - amino - 2 - (3 - carbomethoxythioureido) 4- propylthiobenzene (3.0 g) in methanol (75 ml) there is added 2thiophenecarboxyaldehyde (1.12 g). The solution immediately changes to a yellow color and within 15 minutes a precipitate forms. The suspension is stirred at 5 C for one hour and at room temperature for 24 hours. The solid is collected by filtration and dried to afford 1.05 g of 1 - imino - (2 - thienyl)methyl- 2 - (3 - carbomethoxythioureido) - 4 - propylthiobenzene, m.p. 1230-1240C.

Elemental analysis for C,7H19N302S3 Calc.: C, 51.88; H,4.87; N, 10.68 Found: C,51.52; H,4.92; N, 10.63 Step B-1 - Imino - (2 - thienyl)methyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - propylthiobenzene To a mixture of 1 - imino - (2 - thienyl) - methyl - 2 - (3 carbomethoxythioureido) - 4 - 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 and dried to afford 0.55 g of 1 - imino - (2 - thienyl)methyl - 2 - (3 - carboxymethoxy S - methylisothioureido) - 4 - propylthiobenzene, m.p. 95 C (dec).

EXAMPLE 21 1 -Imino-(p-chlorophenyl)methyl-2-(3-carbomethoxy-S- methylisothioureido)-4-phenylthiobenzene Step A--l - Imino - (p - chlorophenyl)methyl - 2 - (3 carbomethoxythioureido) - 4 - phenylthiobenzene To an ice-cooled solution of 1 - amino - 2 - (3 - carbomethoxythioureido) 4 - phenylthiobenzene (3.33 g) in anhydrous methanol (300 ml) is added finely powderedp-chlorobenzaldehyde (1.4 g). The solution is stirred at 50C for one hour (a precipitate begins to form after 15 minutes). The solid formed is collected by filtration and dried to afford 2.6 g of 1 - imino - (p - chlorophenyl) - methyl - 2 (3 - carbomethoxythioureido) - 4 - phenylthiobenzene, m.p. l700-l720C.

Step B-l - Imino - (p - chlorophenyl)methyl.- 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - phenylthiobenzene To a suspension of 1 - imino - (p - chlorophenyl)methyl - 2- (3 carbomethoxythioureido) - 4 - phenylthiobenzene (1.6 g; .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 within five minutes and the suspension is stirred at room temperature for 30 minutes. The precipitate is collected and dried to afford 1.02 g of 1 - imino - (p - chlorophenyl)methyl - 2 (3 - carbomethoxy - S - methylisothioureido) - 4 - phenylthiobenzene, m.p.

1350-1360C.

Elemental analysis for C23H20C1N3O2S2 Calc.: C, 58.77; H, 4.29; N, 8.94 Found: C, 57.90; H, 4.20; N, 8.77 EXAMPLE 22 3-Imino-(2-thienyl)methyl-4-(3-carbomethoxy S-methylisothioureido)benzophenone A mixture of 3 - imino - (2 - thienyl)methyl - 4 - (3 carbomethoxythioureido)benzophenone (l.0g; 0.0624 mole) in acetone (12 ml) and water (4 ml) containing aqueous sodium hydroxide (0.22 g; 0.0028 mole; 50%) is stirred at room temperature for one hour and.methyl iodide (0.4 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 - carbomethoxy S - methylisothioureido)benzophenone, m.p. 1680--170"C (dec); 67% yield.

EXAMPLE 23 1 -Iminophenylmethyl-2-(3-carbomethoxy-S- allylisothioureido)-4-propylthiobenzene To a suspension of 1 - iminophenylmethyl - 2 - (3 carbomethoxythioureido) - 4 - propylthiobenzene (1.0 g) in acetone (30 ml) and water (10 ml) there is added aqueous sodium hydroxide (0.21 g). The mixture is stirred at room temperature for one hour (a solution forms 20 minutes after the addition of sodium hydroxide) and to it there is added allyl bromide (0.36 g). The solution is stirred at room temperature for two hours and is then poured into water (300 ml). The mixture is stirred at room temperature for 24 hours and is vacuum filtered. The tacky yellow solid is stirred in hexane (50 ml) and is filtered to yield 0.35 g of 1 - iminohexylmethyl - 2 - (3 - carbomethoxy - S - isothiouredio) - 4 propylthiobenzene, m.p. 700--720C.

In a manner similar to that described in the written examples, all of the 2-imino substituted thioureidobenzenes (I) of this invention may be prepared by beginning with an appropriately substituted 1 ,2-diaminobenzene compound and following substantially the procedures described herein. The following equation illustrates the various reactions which may be employed and taken together with Table 1 infra, depict the starting materials , intermediates and final products obtained.

x II ;NH2 0 S=C=NCOR1 / NH IV / Va 2 R2 CHO x Y NH2 N=CHR2 NHS;NHCo,R1 NH2 8 0 2 O vb RCHO 1 -Base x 2 -R-Halo or - N=CHR2 RSO3R or RS04R 1 H1CNHC02R1 II S 11i -Base 2 -R-Halo or X RS03R or RSO4R NH R2CHO 5X\ NHZ N=CHR2 NHCHF=NCo2,1 IIa SR I SR TABLE I Ex.

No. R R R

0 24 -C2H5 -CH, (5 )-C t 25 -C3H7 -C2H5 g ii 26 -CE9 -n-C3H7 27 -C5H11 -iso-C3H7 3t 28 -C6 -g-C4H9 4 Bt 29 -C7E15 -so-C4H9 by 3 I, 30 -C8H17 -tert-CII9 H3 II 31 -(CH2)2CH=CH2 cyclo-C5H9 d H3 32 -(CE2)3cH=cH2 cvclo-C6R11 33 -(CH2)4CH=CX2 -CH3 4 C2E5 3L (CHk)CH:CH -CH3 2R5 C2H5 35 (CH)6ci C-2 -CH3 4 t 36 -CH,CCS -CH, 227 (5)0 36 -CH2C-CH -CH3 m (s)-c 4 TABLE I (cont.) Ex.

R R R X No.

47 -CH2CH2cH2 4 -tert-C4H9 < (.5)-SCN NC 48 -QE2 o Cl -tert-C4Hg ThocH3 (5) -SO TABLE I (cont.) Ex.

No. R R R X

(5)-S02 49 -CH2 o CH3 -CH3 b OCH3 0Cit3 0 50 -CH2CX2 o OCE3 CR3 y (4)-SO t c L 3 11 51 (cm2)3 -CR3 (5 > 4 CH3CO 52 -(CX2)4-0 t -CH3 (4) -SCH, 53 (CR2)5 e cyclo-c5-n F (4)-SC3H7 3 J 7 54 -(CE2)6-0 t evclo-C5H9 + H3 (5) 5003117 55 -CH2 -n-C 3117 F3 (5) F 80,CH3 56 (CE2)2 C -n-C3H7 -n-C3H7 (5) -302C3it7 0 57 -CE2 e -CH3 -n-C4Hg (4) -NLIcCa, 0 58 (cue2)2 e -C2H5 -n-C5S11 (5) NHC0ll (CH)3 /1 59 -(CH2)3CS -CH3 -2-C5E11 (4) 11 r? o it 60 (CH2)4C.J -CH3 ~t C1 (4) C-OC2H5 61 -(CH2)5cN -CH3 4 ( 5) -IE-0-CHz 3 TABLE I (cont.) Ex.

No. R R R X

TABLE I (cont.) Ex.

No. R R R X

TABLE I (cont.) Ex.

No. R R R X

91 -C3H7 tert-C4Hg n N (5)-C3H7 92 -CH3 tert-C4Hg t N (4)-C4Hg 93 -C4 H9 tert-C4H9 (4)-C2H5 N EXAMPLE 94 1 -Imino(2-furylmethyl)-2-(3-carbomethoxy- S-benzylisothioureido)benzene To 100.0 g (0.33 mole) of imino(2- furylmethyl)- 2- (3 carbomethoxythioureido)benzene and 50.0 g (0.395 mole) of benzyl chloride in 275 ml of dimethyl sulfoxide is slowly added 15.0 g (0.375 mole) of sodium hydroxide in 260 g of water. The resulting mixture is stirred for + hour and the yellow precipitate is separated by filtration and recrystallized from 800 ml of methylene chloridehexane (1:1) to give 91.1 g (70.1%) of 1 - imino - (2 - furylmethyl) - 2 - (3 carbomethoxy - S - benzylisothioureido)benzene m.p. 112 -114 C.

Elemental analysis for C21HtgNOS 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-(3-carbomethoxy S-butylisothioureido)benzene To 5.0 g (0.0165 mole) of 1 - imino(2- furylmethyl)- 2 - (3 - carbomethoxythioureido)benzene and 3.6 g (0.01975 mole) of iodobutane in 80 ml of N,N-dimethylformamide is added 0.7 g (0.0175 mole of sodium hydroxide in 20 ml of water. The resulting mixture is stirred for + 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. 86-70C. Recrystallization from ether-hexane affords 1 - imino(2 - furylmethyl) - 2 - (3 - carbomethoxy - S butylisothioureido)benzene m.p. 84 -85 C.

Elemental analysis for C18H21N3O3S Calc.: C,60.15; H,5.89; N,11.69; 0,13.35; S,8.92 Found: C, 59.98; 11, 5.93; N, 11.77; 0,13.83; S,8.90 EXAMPLE 96 1-Imino(2-furylmethyl)-2-(3-carbomethoxy S-methylisothioureido)benzene A mixture of 3.03 g (.01 mole) 1 - imino(2 - furylmethyl)- 2 - (3 carbomethoxythioureido)benzene, 1.38 g (.01 mole of potassium carbonate, and 1.42 g (.01 mole) of methyl iodide in 50 ml of acetone is refluxed and stirred for 1 hour. The suspension is allowed to stand at room temperature for 24 hours and is vacuum filtered. The filtrate is concentrated in vacuo and the residue orange semisolid 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 product, m.p. 97 -105 C.

A sample of the product recrystallized from ether affords 1 - imino(2 - furylmethyl)2 - (3 - carbomethoxy - S - methylisothioureido)benzene as a fluffy yellow solid, m.p. 940-970C.

Elemental analysis for C,5H,5N303S Calc.: C, 56.77; H, 4.76; N, 13.24; S, 10.10 Found: C, 57.22; H,4.84; N, 13.60; S, 10.43 EXAMPLE 97 l-Imino-(p.chlorophenyl)methyl.2-(3-carbomethoxy- S.methylisothioureido)-4.propylthiobenzene To a mixture of 1 - imino - (p - chlorophenyl)- methyl - 2 - (3 - carbomethoxythioureido) - 4 - propylthiobenzene (4.22 g; .01 mole) in acetone (25 ml) and water (10 ml) there is added 50% aqueous sodium hydroxide (0.8 g; .01 mol). The mixture is stirred at room temperature for one hour and to it there is added dimethyl sulfate (1.26 g; .01 mole). The reaction mixture is stirred at room temperature for one hour and the precipitate collected and dried to afford 1 imino - (p - chlorophenyl)methyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - propylthiobenzene.

EXAMPLE 98 1 -Iminophenylmethyl-2-(3-carbomethoxy.S methyl-isothioureido)-4-propylthiobenzene To a solution of I - iminophenylmethyl - 2 - (3 - carbomethoxythioureido) 4 - propylthiobenzene (3.88 g; .01 mol) in acetone (40 ml) and water (10 ml) there is added calcium hydroxide (0.74 g; .01 mol). The mixture is stirred at room temperature for 4 hours and then is added methyl iodide (1.42 g; .01 mol). The mixture is stirred at room temperature for 4 hours and the precipitate collected and dried to afford 1 - iminophenylmethyl- 2 - (3 - carbomethoxy - Smethylisothioureido) - 4 - propylthiobenzene.

EXAMPLE 99 I -Iminophenylmethyl-2-(3-carbomethoxy-S- methylisothioureido)-4-propylthiobenzene To a solution of 1 - iminophenylmethyl - 2 - (3 - carbomethoxythioureido) 4 - propylthiobenzene (3.88 g; .01 mol) in dimethylformamide (40 ml) and water (10 ml) there is added calcium hydroxide (0.74 g; .01 mol). The mixture is stirred at room temperature for four hours and to it there is added dimethylsulfate (1.26 g).

The mixture is stirred at room temperature for four hours and the precipitate collected and dried to afford 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - propylthiobenzene.

EXAMPLE 100 I -Imino-(o-chlorophenyl)methyl-2-(3-carbomethoxy-S- methylisothioureido)-4.propylthiobenzene To a mixture of 1 - imino - (o - chlorophenyl)methyl - 2 - (3 - carbomethoxythioureido) - 4 - propylthiobenzene (4.22 g; .01 mol) in acetone 25 ml) and water (10 ml) there is added 50% aqueous sodium hydroxide (0.8 g; .01 mol). The mixture is stirred at room temperature for one hour and there is then added dimethyl sulfite (1.1 g; .01 mol). The mixture is stirred at room temperature for 3 hours and the precipitate collected and dried to afford 1 - imino - (o chlorophenyl) - methyl - 2 - (3 - carbomethoxy - S - methylisothioureido) - 4 propylthiobenzene.

EXAMPLE 101 1 -Iminophenylmethyl.2.(3-carbomethoxy-S- methylisothioureido)-5-benzoylbenzene To a solution of 1 - iminophenylmethyl - .- (3 - carbomethoxythioureido) 5 - benzoylbenzene (4.33 g; .01 mol) in dimethylformamide (50 ml) and water (5 ml) there is added calcium hydroxide (0.74 g; .01 mol). The mixture is stirred at 300C for 2 hours and to it there is added dimethyl sulfite (1.1 g; .01 mol). The mixture is stirred at room temperature for 3 hours and the precipitate collected and dried to afford 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 5 - benzoylbenzene.

EXAMPLE 102 1 -Imino-(p-chlorophenyl)methyl-2-(3-carbomethoxy-S- methylisothioureido)-4-phenylthiobenzene To a mixture of 1 - imino - (p - chlorophenyl)- methyl - 2- (3 carbomethoxythioureido) - 4 - phenylthiobenzene (4.56 g; .01 mol) in acetone (35 ml) there is added 57% sodium hydride (0.42 g; .01 mol) (oil dispersion). The mixture is stirred at room temperature for one hour and there is then added methyl iodide (1.42 g; .01 mol). The mixture is stirred at room temperature for one hour and is poured into an excess of water. The suspension is filtered and the precipitate dried to afford 1 - imino - (p - chlorophenyl)methyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - phenylthiobenzene.

EXAMPLE 103 3-Imino-(o-chlorophenyl)methyl-4-(3-carbomethoxy- S-methylisothioureido)benzophenone To a mixture of 3- imino - (o- chlorophenyl)methyl - 4- (3- carbomethoxythioureido)benzophenone (4.52 g; .01 mol) in l,2-dimethoxyethane (50 ml) there is added 57% sodium hydride (0.42 g; .01 mol) (oil dispersion). The mixture is stirred at room temperature for one hour and there is then added dimethyl sulfate (1.26 g; .01 mol). The mixture is stirred at room temperature for one hour and is poured into an excess of water. The suspension is filtered and the filter cake dried to afford 3 - imino - (o - chlorophenyl)methyl - 4 - (3 carbomethoxy - S - methylisothioureido)benzophenone.

EXAMPLE 104 3-Imino-(o-nitrophenyl)methyl-4-(3-carbomethoxy S-methylisothioureido)benzophenone To a mixture of 3- imino - (o - nitrophenyl)methyl - 4- (3carbomethoxythioureido)benzophenone (4.62 g; .01 mol) in dimethyl formamide (40 ml) there is added 57% sodium hydride (0.42 g; .01 mol) (oil dispersion). The mixture is stirred at room temperature for one hour and to it there is added dimethyl sulfite (1.1 g; .01 mol). The mixture is stirred at room temperature for 1+ hours and is poured into an excess of water. The suspension formed is vacuum filtered and the filter cake dried to afford 3 - imino - (o - nitrophenyl)methyl -4 (3 - carbomethoxy - S - methylisothioureido)benzophenone.

EXAMPLE 105 3-Imino-(3,4-dichlorophenyl)methyl-4-(3-carbomethoxy S-methylisothioureido)benzophenone To a mixture of 3- imino - (3,4 - dichlorophenyl)methyl - 4- (3- carbomethoxythioureido)benzophenone (4.86 g; .01 mol) in acetone (50 ml) there is added calcium hydride (0.42 g- .01 mol). The mixture is refluxed for one hour and then cooled to room temperature. To the mixture is added methyl iodide (1.42 g; .01 mol). The mixture is stirred 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 3 - imino - (3,4 - dichlorophenyl)methyl - 4 - (3 - carbomethoxy S - methylisothioureido)benzophenone.

EXAMPLE 106 3-Imino-(4-methoxyphenyl)methyl-4-(3-carbomethoxy- S-methylisothioureido)benzophenone To a mixture of 3- imino - (4- methoxyphenyl)methyl - 4- (3 carbomethoxythioureido)benzophenone (4.47 g- .01 mol) in l,2-dimethoxyethane (50 ml) there is added calcium hydride (0.42 g; .01 mol). The mixture is refluxed for one hour and is cooled to room temperature. To the mixture there is added dimethyl sulfate (1.26 g; .01 mol). The mixture is stirred 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 3 - imino - (4 - methoxyphenyl)methyl 4 - (3 - carbomethoxy - S - methylisothioureido)benzophenone.

EXAMPLE 107 3-Imino-(4-nitrophenyl)methyl-4-(3-carbomethoxy S-methylisothioureido)benzophenone To a mixture of 3 - imino - (4- nitrophenyl)- methyl - 4- (3 carbomethoxythioureido)benzophenone (4.62 g; .01 mol) in acetone (50 ml) there is added calcium hydride (0.42 g; .01 mol). The mixture is refluxed for one hour and is cooled to room temperature. To the mixture there is added dimethyl sulfite (1.1 g; .01 mol). The mixture is stirred 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 3 - imino - (4 - nitrophenyl)methyl - 4 - (3 - carbomethoxy - S methylisothioureido)benzophenone.

EXAMPLE 108 1 -Iminophenylmethyl-2-(3.carbomethoxy.S- methylisothioureido)-4-propylthiobenzene To a mixture of 2 - (3 - carbomethoxy - S - methylisothioureido) - 4 propylthioaniline (3.13 g; .01 mol) in methanol (25 ml), cooled to 50C, there is added benzaldehyde (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 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - methylisothioureido) - 4 propylthicbenzene.

EXAMPLE 109 1 ID=29.5

EXAMPLE 114 1-Iminopropyl-2-(3-carbomethoxy-S-methylisothioureido) 4-propylthiobenzene Step A-1 - Iminopropyl - 2- (3 - carbomethoxythioureido) - 4 propylthiobenzene To a suspension of 2 - (3 - carbomethoxythioureido) - 4 - propylthioaniline (2.99 g; .01 mole) in methanol (50 ml), cooled to 50C, there is added propionaldehyde (0.64 g; .01 mole). The mixture is stirred at 5 C for 2 hours and the solution formed is stirred at room temperature for I week. The suspension that forms is vacuum filtered and the filter cake is washed with ether and dried to afford 1 - imino propyl - 2 - (3 - carbomethoxythioureido) - 4 - propylthiobenzene (1.3 g; 38.3%), m.p. 163 168 C (dec).

Elemental analysis for C15H21N3O2S2 Calc.: C, 53.07; 11, 6.24: N, 12.38 Found: C, 52.72; H, 6.32; N, 12.38 Step B-l - Iminopropyl - 2 - (3 - carbomethoxy - S - methylisothioureido) -4 propylthiobenzene To a suspension of 1 - iminopropyl - 2 - (3 - carbomethoxythioureido) - 4 propylthiobenzene (1 g; .00295 mole) in acetone (30 ml) and water (15 ml) there is added 50.8% aqueous sodium hydroxide (0.23 g; .00295 mole). The solution that forms is stirred at room temperature for one hour and to it there is added methyl iodide (0.42 g; .00295 mole). The turbid solution formed is stirred at room temperature for 30 minutes and is poured into water (500 ml). The suspension formed is stirred at room temperature for one hour and is vacuum filtered. The filter cake is dried to afford 1 - imino - propyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - propylthiobenzene (0.85 g; 81.5%), m.p. 85-900C (dec).

Elemental analysis for C16H23N3O2S2 Calc.: C, 54.36; H, 6.56; N, 11.89 Found: C, 53.96; H, 6.60; N, 11.63 EXAMPLE 115 1 -Imino-(4-methyl)phenylmethyl-2-(3-carbomethoxy- S-methylisothioureido)-4-propylthiobenzene Step A-l - Imino(4 - methyl)phenylmethyl - 2 - (3 - carbomethoxythioureido 4 - propylthiobenzene To a suspension of 2 - (3 - carbomethoxythioureido) - 4 - propylthioaniline (9.0 g; .03 mole) in methanol (100 ml, cooled to 100C, there is added pmethylbenzaldehyde (3.6 g; .03 mole). The mixture is stirred at 100C for I hr. and at room temperature for 18 hrs. The suspension that forms is vacuum filtered and the filter cake is air dried to afford 1 - imino - (4 - methyl)phenylmethyl - 2 - (3 carbomethoxythioureido) - 4 - propylthiobenzene (10.75 g; 89%), m.p. 135 141"C.

Elemental analysis for C20H23N3O2S2 Calc.: C, 59.82; H, 5.77; N, 10.46 Found: C, 59.32; H,5.87; N, 10.75 Step B-I - Imino(4 - methyl)phenylmethyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - propylthiobenzene To a suspension of 1 - imino(4- methyl)phenylmethyl - 2 - (3 - carbomethoxythioureido) - 4 - propylthiobenzene (4.02 g; .01 mole) in 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 stirred at room temperature for 1 hr. and is vacuum filtered. The filter cake is air dried to afford 1 - imino(4 - methyl)phenylmethyl - 2 - (3 - carbomethoxy S - methyl - isothioureido) - 4 - propylthiobenzene (3.6 g; 86.6%), m.p. 113 115 C.

Elemental analysis for C21 H25N3O2S2 Calc.: C, 60.69; H,6.06; N, 10.11 Found: C, 60.75; H, 6.29; N, 10.47 EXAMPLE 116 1-Imino-(4-methoxy)phenylmethyl-2-(3-carbomethoxy S-methylisothioureido)-4-propylthiobenzene Step A-I - Imino - (4 - methoxy)phenylmethyl - 2 - (3 carbomethoxythioureido) - 4 - propylthiobenzene To a suspension of 2 - (3 - carbomethoxy - thioureido) - 4 - propylthioaniline t9.0 g; .03 mole) in methanol (100 ml) cooled to 100C, there is addedp-anisaldehyde (4.08 g; .03 mole). The mixture is stirred at 100C 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 - imino - (4 - methoxy)phenylmethyl - 2 - (3 carbomethoxythioureido) - 4 - propylthiobenzene (9.9 g; 79%), m.p. 1410-1440C.

Elemental analysis for C20H23N303S2 Calc.: C, 57.53; H,5.55; N, 10.06 Found: C, 57.19; H, 5.67; N, 10.25 Step B-1 - Imino - (4 - methoxy)phenylmethyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - propylthiobenzene To a suspension of 1 - imino - (4 - methoxy)phenylmethyl - 2 - (3 - carbomethoxythioureido) - 4 - propylthiobenzene (4.18 g; .01 mol) in acetone (60 ml) and water (20 ml) there is added 50% aqueous sodium hydroxide (.08 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 stirred at room temperature for 1 hr and is vacuum filtered. The filter cake is air dried to afford 1 - imino(4- methoxy)phenylmethyl - 2 - (3 - carbomethoxy - S - methylisothioureido) - 4 - propylthiobenzene (2.3 g; 53%), m.p. 9092.

Elemental analysis for C21H25N3O3S2 Calc.: C, 58.44; H, 5.84, N, 9.74 Found: C, 58.38; H, 5.94; N, 9.91 EXAMPLE 117 I -Imino(4-nitro)phenylmethyl-2-(3-carbomethoxy-S methylisothioureido)-4-propylthiobenzene Step A-l - Imino - (4 - nitro)phenylmethyl -2 - (3 - carbomethoxythioureido) 4 - propylthiobenzene To a suspension of 2 - (3 - carbomethoxythioureido) - 4 - propylthioaniline (4.0 g; .013 mole) in methanol (35 ml) there is added a solution of pnitrobenzaldehyde (2.0 g; .013 mole) in methanol (35 ml). The mixture is stirred at room temperature for 1 hr and is vacuum filtered. The filter cake is washed with methanol and dried to afford 1 - imino(4 - nitro)phenylmethyl- 2 - (3 - carbomethoxythioureido) - 4 - propylthiobenzene (5.3 g; 94%), m.p. 1980-2000C.

Elemental analysis for C19H20N4O4S2 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 - carbomethoxy - S methylisothioureido) - 4 - propylthiobenzene A mixture of 1 - 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 120C. To the mixture there is added methyl iodide (1.4 g; .01 mole) and it is stirred at 130C to 200C for 2 hrs. The suspension that forms is vacuum filtered and the filter cake is washed with acetone and dried to afford 1 - imino(4 - nitro)phenylmethyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - propylthiobenzene (3.5 g; 78%), m.p. 1350-1370C dec.

Elemental analysis for C20H22N4O4S2 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-propylthiobenzene Step A-l - Imino - (2 - furylmethyl) - 2 - (3 - carbomethoxythioureido) - 4 propylthiobenzene To a suspension of 2 - (3 - carbomethoxythioureido) - 4 - propylthioaniline (6.0 g; .02 mole) in methanol (200 ml), cooled to 100C there is added 2 furfuraldehyde (1.92 g, 0.02 mole). The mixture is stirred at 10 C 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 carbomethoxythioureido) - 4 - propylthioaniline (5.6 g; 74%), m.p. 131 -133 C.

Elemental analysis for C17H19N3O3S2 Calc.: C, 54.09; H, 5.07; N, 11.13 Found: C, 53.68; H, 5.11 N, 11.13 Step B-1 - mino - (2 - furylmethyl) - 2 ~ (3 - carbomethoxy - S methylisothioureido) - 4 - proylthiobenzene To a suspension of 1 - imino - (2 - furylmethyl)- 2- (3 carbomethoxythioureido) - 4 - propylthiobenzene (3.77 g; 0.1 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- hrs. and the suspension that forms is vacuum filtered. The filter cake is air dried to afford 1 - imino - (3 furylmethyl)- 2- (3 - carbomethoxy - S- methylisothioureido) - 4 propylthiobenzene (2.65 g; 67.7%), m.p. 960--980C.

Elemental analysis for C1 8H21N3O3S2 Calc.: C,55.22; H,5.41; N, 10.73 Found: C,54.71; H,5.39; N, 10.51 EXAMPLE 119 When the procedures of the above examples are followed and by employing known starting diamine precursors, the following products may be obtained: 3 - iminophenylmethyl - 4 - (3 - carboethoxy - S - methylisothioureido)benzophenone; 3 - (imino(p - chloro)phenylmethyl - 4 - (3 - carbopropoxy - S methylisothioureido)benzophenone; 1 - iminophenylmethyl - 2 - (3 - carbo - isopropoxy - S methylisothioureido) - 4 - propylthiobenzene; 1 - iminophenylmethyl - 2 - (3 - carbobutoxy - S - allylisothioureido) - 4 phenylthiobenzene; 3 - iminophenylmethyl - 4 - [3 - carbo - (2 - methoxy)ethoxy - S methylisothioureido]benzophenone; 1 - iminophenylmethyl - 2 - [3 - carbo - (2 - methoxy)ethoxy - S methylisothioureido] - 4 - propylthiobenzene; 3 - iminophenylmethyl] - 4 - (3 - carbomethoxy - S - methylisothioureido) 4' - chlorobenzophenone; 3 - imino - (p - chlorophenyl)methyl - 4 - (3 - carbomethoxy - S allylisothioureido) - 4' - fluorobenzophenone; 3 - iminophenylmethyl - 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 methylisothioureido) - 3' - trifluoromethylbenzophenone; 3 - iminophenylmethyl - 4 - (3 - carbomethoxy - S - methylisothioureido)propiophenone; 3 - iminophenylmethyl - 4 - (3 - carbomethoxy - S - allylisothioureido)butyrophenone; 3- imino - p - nitrophenymethyl- 4- (3 - carbomethoxy - S butylisothioureido)valerophenone; 1 - cyclopropylcarbonyl - 3 - iminophenylmethyl - 4 - (3 - carbomethoxy S - methylisothioureido)benzene; 1 - cyclopentylcarbonyl - 3 - imino - (p - chloro)phenylmethyl - 4 - (3 carbomethoxy - S - butylisothioureido)benzene; 1 - (2 - thienyl) - 3 - imino - (p - methyl)phenylmethyl - 4 - (3 carbomethoxy - S - methylisothioureido)benzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - methylisothioureido) 4 - (4 -cyanophenylthio)benzene, I - iminophenylmethyl - 2 - (3 - carbomethoxy - S - butylisothioureido) 4 - (3 - cyanophenylthio)benzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - butylisothioureido) 4 - (4 - methylisothiophenylthio)benzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - methylisothioureido) 4 - (3 - methylthiophenylthio)benzene; 1 - imino - (p - chlorophenyl)methyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - (4 - acetylphenylthio)benzene; 1 - imino - (p - chlorophenyl)methyl - 2 - (3 - carbomethoxy - S allylisothioureido) - 4 - (4 - methoxycarbonylphenylthio)benzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - methylisothioureido) 4 - (4 - acetylaminophenyl)benzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - butylisothioureido) 4 - (4 - phenoxyphenylthio)benzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - methylisothioureido) 4 - (4 - cyanophenylsulfinyl)benzene; 1 - imino - (p - chlorophenyl)methyl - 2 - (3 - carbomethoxy - S butylisothioureido) - 4 - (4 - acetylphenylsulfinyl)benzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - methylisothioureido) 4 - (4 -cyanophenylsulfonyl)benzene; 1 - imino - (p -chlorophenyl)methyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - (4 - acetylphenylsulfonyl)benzene; 1 - imino - (p -chlorophenyl)methyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - (phenylsulfinyl)benzene; 1 - imino - (p - chlorophenyl)methyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - (phenylsulfonyl)benzene; 1 - imino - (p - chlorophenyl)methyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 5 - (4 - acetylphenylsulfonyl)benzene; 1 - imino - (o - chlorophenyl)methyl - 2 - (3 - carbomethoxy - S methylisothioureido - 5 - (4 - cyanophenylsulfonyl)benzene; 1 - iminophenylmethyl - 2 ~ (3 - carbomethoxy - S - methylisothioureido) 5 - (4 - acetylphenylsulfinyl)benzene; 1 - iminophenylmethyl) - 2 - (3 - carbomethoxy - S - methylisothioureido) 5 - (4 - cyanophenylsulfinyl)benzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - methylisothioureido) 5 - phenoxysulfonylbenzene; 1 - imino - p - chlorophenylmethyl) - 2 - (3 - carbomethoxy - S methylisothioureido= - 5 - (p - chlorophenoxysulfonyl)benzene; 1- (imino - p - chlorophenylmethyl) - 2 - (3 - carbomethoxy - S butylisothioureido - 5 - (3 - chlorophenoxysulfonyl)benzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - benzylisothioureido 5 - (2 - chlorophenoxysulfonyl)benzene; 1 - imino - o - chlorophenylmethyl) - 2 - (3 - carbomethoxy - S allylisothioureido) - 5 - (3,5 -dichlorophenoxysulfonyl)benzene; 1 - (imino - p - nitrophenylmethyl) - 2 - (3 - carbomethoxy - S methylisothioureido) - 5 - (4 - methoxyphenoxysulfonyl)benzene; 1 - (imino - p- methoxyphenyl)- 2- (3 - carbomethoxy - S methylisothioureido) - 5 - (3 - cyanophenoxysulfonyl)benzene; 1 - iminophenyl - 2 - (3 - carbomethoxy - S - methylisothioureido) - 5 - (3 trifluoromethylphenoxysulfonyl)benzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - methylisothioureido) 5 - phenylsulfonyloxybenzene; 1 - imino- (p - chlorophenyl)methyl - 2 - (3 -.carbomethoxy - S allylisothioureido) - 5 - (4 - chlorophenyl)sulfonyloxybenzene; 1 - imino - (o - chlorophenyl)methyl - 2 - (3 - carbomethoxy - S butylisothioureido) - 5 - (3 - chlorophenyl)sulfonyloxybenzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - butylisothioureido) 5 - (3,5 - dichlorophenyl)sulfonyloxybenzene; 1 - imino - (p - nitrophenyl)methyl - 2 - (3 - carbomethoxy - S benzylisothioureido) - 5 - (4 - methylphenyl)sulfonyloxybenzene; 1 - imino - (p - methoxyphenyl)methyl - 2 - )3 - carbomethoxy - S allylisothioureido) - 5 - (3 - trifluorophenyl)sulfonyloxybenzene; 1 - iminophenylmethyl - 2 - (3 - carbomethoxy - S - methylisothioureido) 5 - (4 - methoxyphenyl)sulfonyloxybenzene.

Examples of other X substitutents on known diamines include 4- and 5propoxyy; 4- and 5-phenoxy; 4- and 5-(pyrid-2-yloxy); 4-(4-chlorophenoxy);4 (trifluoromethylphenoxy); 5-(3-chloropropoxy); 5 - (2 - phenylethoxy); 5 - (3 phenylprop - 2 - en - 1 - yloxy); 5 - (4 - methylphenoxy); 5 - (3-methylphenoxy); 5 - (2 - methylphenoxy); 5 - (3 - methylthiophenoxy); 5 - (propargylthio); 5 (but -3 -3n -1 -yl -thio); 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); 4 -pyrimidin -2 -yl -thio)M 5 -(thien -2 -yl -thio); 5 - (fur - 2 - yl - thio); 5 - (3 - chloropropylthio); 4 - (3 - chloropropylthio); 4 (3 - chloroprop - 2 - en - l - yl - thio); 4- (2- cyanoethylthio); 5 - (2,3 dichloropropyl - 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; 3,984,561; 3,993,768; 3,996,368; 3,996,369: 4,002,640: French Pat. Nos. 2,248,037; 2,270,861 and Netherlands Pat. Specification No. 4,701,797.

These patents, insofar as they are related to the disclosure of the diaminobenzene precursors, are hereby incorporated by reference.

Claims (27)

WHAT WE CLAIM IS:

1. A compound Formula I below (or a pharmaceutically or agronomically acceptable acid addition salt, or amide derivative, of a compound of Formula I)

wherein R is alkyl, alkenyl, alkynyl, 2,6-dichlorophenyl, optionally substituted aralkyl, mononuclear aryloxy(C3-C6) alkyl, cycloalkylalkyl, cyano(C3-C6)alkyl, hydroxy(C3-C8)alkyl, aralkenyl, alkoxyalkyl, alkoxycarbonylalkyl, phthalimido(C1-C6)alkyl or phenoxycarbonylalkyl; R is alkyl, cycloalkyl or alkoxyalkyl having 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties; R is alkyl, optionally substituted aryl or optionally substituted heteroaryl and X is hydrogen, nitro, halo, (C2Cs)aikanoyl, alkyl, thiocyanato, alkylcarbonylamino having 1 to 6 carbon atoms in the alkyl group, alkoxycarbonylamino having 1 to 4 carbon atoms in the alkoxy group, cycloalkylcarbonylamino, a radical of the formula: YS(O)n (wherein Y is an optionally substituted group selected from alkyl, alkenyl, alkynyl, cycloalkyl, a 5- or 6-membered heterocycle and mononuclear aryl and n is 0 to 3), a radical of the formula:

(wherein Y' is an optionally substituted group selected from mononuclear aryl, cycloalkyl and a 5- or 6-membered heterocycle) or a radical of the formula: Y"O (wherein Y" is an optionally substituted group selected from alkyl, alkenyl, mononuclear aralkyl and a 5- or 6-membered heterocycle).

2. A compound, acid addition salt or amide derivative according to Claim 1 wherein the compound of Formula I is also of the formula:

wherein R3 is (C1-C8)alkyl, (C3-C8)alkenyl, (C3-C8)alkynyl, benzyl, 2,6dichlorobenzyl, phenethyl, cycloalkyl(C1-C6)alkyl of from 5 to 6 nuclear atoms, phenoxy(C3-C6)alkyl, cyano(C3-C6)alkyl, alkoxycarbonylalkyl having from 3 to 6 carbon atoms in each of the alkoxy and alkyl groups, phthalimido(C1-C6)alkyl, phenyl(C3-C6)alkenyl or hydroxy(C3-C8)alkyl; R4 is (C1-C6)alkyl; R5 is optionally substituted aryl of up to 14 nuclear carbon atoms or heteroaryl having 5 or 6 nuclear atoms containing from 1 to 3 hetero atoms selected from oxygen, nitrogen and sulfur, and X' is in the 4 or 5 position of the benzene ring and is selected from hydrogen, (C1-C4)alkyl carbonylamino, (C1- C4)alkoxycarbonylamino, (C1-C5)alkoxy, (C2-C5)alkanoyl, propylthio, propylsulfinyl, propylsulfonyl, propylsulfonyloxy, propoxysulfonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy or benzoyl.

3. A compound, acid addition salt or amide derivative according to Claim 2, wherein R5 is nitrophenyl dimethylaminophenyl, (C1-C5)alkoxyphenyl, cyanophenyl, acetamidophenyl, methylenedioxyphenyl, phenyl, halophenyl, furyl, thienyl, (C1-C6)alkyl phenyl or dihalophenyl.

4. A compound, acid addition salt or amide derivative according to Claim 3, wherein X1 is hydrogen, 4-benzoyl, 5-propylthio or 5-phenylthio.

5. A compound, acid addition salt or amide derivative according to Claim 1, wherein R is (C12-C8)alkyl, (C3-C8)alkenyl, (C3-C8)alkynyl, polynuclear aralkyl containing 2 or 3 alkyl carbon atoms, mononuclear aralkyl containing up to 3 alkyl carbon atoms and which may be optionally substituted with up to 3 of the same or different substituents selected from halo, alkyl, alkoxy, nitro and cyano, mononuclear aryloxy(C3-C6)alkyl, cycloalkylalkyl containing 5 or 6 cyclic carbon atms and 1 or 2 alkyl carbon atoms, (C1-C8)alkoxy (C1-C8)alkyl, (C1- C6)alkoxycarbonyl (C3-C6)alkyl, phthalimido(C1-C6)alkyl or phenoxycarbonyl (C3-C6)alkyl; R' is (C1-C6)alkyl, cyclopentyl, cyclohexyl or alkoxyalkyl of up to 8 carbon atoms R is (C1-C6)alkyl, phenyl, naphthyl, thienyl, pyridyl, each optionally substituted with up to 3 of the same or different substitutents selected from halo, (C1-C5)alkyl, (C1-C5)alkoxy, di(C1-C8alkyl)amino, (C2-C5)alkanoylamino, phenoxy, benzyloxy, methylenedioxy, phenylthio(C1-C8)alkyl, cyano, nitro, (C1 C8)alkylthio and arylthio and X is (1) hydrogen, (2) nitro, (3) halo, (4) (C1-C5)alkoxy, (5) (C2-C5)alkanoyl, (6) (C1-C4)alkyl, (7) thiocyanate, (8) a group of the formula: Y(SOn) wherein Y is (C1-C5)alkyl, 8C3-C6)alkenyl, (C3-C6)alkynyl, (C3-C7)cycloalkyl, phenyl, pyridyl, thienyl, furyl, pyrimidyl or thiazolyl and n is 0 or an integer of 1 to 3, (9) (C2-C8)alkylcarbonylamino, (10) alkoxycarbonylamino containing 2 to 5 carbon atoms, (11) cycloalkylcarbonylamino containing 5 or 6 carbon atoms in the ring, (12) a group of the formula:

wherein Y' is phenyl, (C3-C7)cycloalkyl, pyridyl, 2-thienyl or furyl or (13) a group of the formula Y"O wherein Y" is (C1-C5)alkyl, (C3-C6)alkenyl, phenyl or benzyl, the Y, Y' and Y" groups as defined above being optionally substituted.

6. A compound, acid addition salt or amide derivative according to Claim 1, wherein: R is (C1-C4)alkyl, aryl(C1-C4)alkyl, (C3-C8)alkenyl or 2,6-dichlorophenyl; R is (C1-C4)alkyl R is phenyl or naphthyl optionally substituted with up to 3 of tha same or different substituents selected from halo, nitro, (C1-C5)alkyl, (C1-C5)alkoxy, di(C1-C4)alkylamino; furyl or thienyl; and X is benzoyl, phenylthio, phenylsulfonyl, (C1-C5)alkylthio, (C1 C5)alkylsulfinyl, (C1-C5)alkylsulfonyl or hydrogen.

7. The compound 3 - imino - (4 - chlorophenyl) methyl - 4 - (3 carbomethoxy - S - methylisothioureido) - benzophenone.

8. The compound 3 - imino - phenylmethyl - 4 - (3 - carbomethoxy - S methylisothioureido)benzophenone.

9. The compound 1 - imino - phenylmethyl - 2 - (3 - carbomethoxy - S methylisothioureido) - 4 - propylthio - benzene.

10. The compound 1 - imino - (4 - chlorophebnyl)methyl - 2 - (3 carbomethoxy - S -methylisothioureido) - 4 - phenylthiobenzene.

11. The compound 1 - imino - (4 - chlorophenyl)methyl - 2 - (3 carbomethoxy - S - methylisothioureido) - 4 - propylthiobenzene.

12. The compound 1 - imino - (2 - furylmethyl) - 2 - (3 - carbomethoxy - S benzylisothioreuio)-benzene.

13. The compound I - imino - (2 - furylmethyl) - 2 - (3 - carbomethoxy - S butylisothioureido) - benzene.

14. The compound 1 - imino - (2 - furylmethyl) - 2 - (3 - carbomethoxy - S methylisothioureido) - benzene.

15. A pharmaceutically or agronomically acceptable acid addition salt or amide derivative of a compound as claimed in any of Claims 7-14.

16. A composition useful in the treatment of helminths which comprises a compound (including an acid addition salt or amide) according to any of the preceding claims and a pharmaceutically acceptable carrier.

17. A method of combating a helminth infection in a host animal (other than a human being) which comprises administering to the animal an effective amount of an anthelmintic comprising or consisting of a compound (including an acid addition salt or amide) according to any of Claims 1--15.

18. A composition according to Claim 15 in unit dosage form.

19. A method according to Claim 17, wherein said compound acid addition salt or amide is administered in an amount from 1 mg to 125 mg per kg of body weight of the host animal.

20. A method of combating phytopathogenic fungi on plants which comprises applying a compound, acid addition salt or amide derivative according to any of Claims 1--15 to the plant habitat, plant seeds or plant foliage.

21. A fungicidal composition comprising a compound (including an addition salt or amide) according to any of Claims 1--15 and an agronomically acceptable carrier therefor.

22. A process for preparing a compound of Formula I in Claim I which comprises treating a compound of the formula:

with a base followed by treatment with a compound selected from those of the formulae RSO3R, RS04R and RX2 wherein R, R' R2 and X are as defined in Claim I and X2 is halo.

23. A process for preparing a compound of the Formula I in Claim 1 which comprises treating a compound of the formula:

with an aldehyde of the formula: R2CHO wherein R, R', R2 and X are as defined in Claim 1.

24. A process according to Claim 22 or 23 as applied to the preparation of a compound according to any of Claims 2-14.

25. A compound according to Claim 1 whenever prepared by a process according to any of Claims 22-24.

26. A compound of Formula I as defined in Claim 1 being any of those individual compounds referred to in the foregoing descriptive portion of this specification with the exception of the compounds claimed in Claims 7-14.

27. A pharmaceutically or agronomically acceptable acid addition salt or amide derivative of a compound as claimed in Claim 26.