Treatment of hypertension with amidinoureas
CROSS REFERENCE TO RELATED APPLICATIONS 
     This is a continuation of application Ser. No. 805,371 filed June 10, 1977 now abandoned which is a continuation of Ser. No. 687,266 filed May 17, 1976 now abandoned which is a continuation of Ser. No. 385,797 filed Aug. 6, 1973 now abandoned which is a continuation-in-part of copending application Ser. No. 291,474 filed Sept. 22, 1972, now abandoned. 
    
    
     SUMMARY OF THE INVENTION 
     This invention describes new substituted phenylamidinourea compounds and processes for their preparation. This invention further provides valuable pharmaceutical preparations which contain substituted phenylamidinourea compounds which possess an effective degree of antihypertensive properties and exert activities on the cardiovascular system. A method for the treatment of hypertensive disorders by the administration of a substituted phenylamidinourea compound is also described. 
     BACKGROUND OF THE INVENTION 
     The pharmaceutical compositions which have been used as antihypertensive agents have included such as the thiazides, reserpine, hydralazine, α-methyl dopa, guanethidine and the like. These compounds, however, while being effective produce undesirable side effects such as electrolyte imbalance, orthostatic hypertension, and gastric secretory and spasmolytic properties. 
     We have unexpectedly found that amidinourea compounds exhibit valuable pharmacologic properties. 
     We have unexpectedly found that the amidinoureas of this invention are useful antihypertensive agents. 
     We have further found that the amidinourea compounds of this invention are novel and can easily be prepared. 
     We have also found that the compounds of this invention have a minimum of the side effects which accompany antihypertensive agents. 
     We have still further found a simple and effective method for the treatment of cardiovascular disorders such as hypertensive disorders. 
     DESCRIPTION AND PREFERRED EMBODIMENT 
     This invention describes a class of novel chemical compounds which comprises a substituted phenyl radical which is further attached to a substituted amidinourea chain. This results in urea and substituted urea type compounds having a phenylamidino or a substituted phenylamidino group attached at one of the nitrogen atoms. This invention also describes the non-toxic pharmaceutically acceptable salts and the method of preparing these substituted phenylamidinourea compounds. 
     The novel compounds of this invention are described by the structural formula I ##STR1## where: X is hydrogen, 
     loweralkyl, 
     halo; 
     Y is hydrogen, 
     halo, 
     haloloweralkyl, 
     nitro, 
     loweralkyl or 
     loweralkoxy; 
     Z is halo, 
     loweralkoxy, 
     loweralkyl, 
     nitro, 
     cyano, 
     haloloweralkyl, 
     haloloweralkoxy or 
     loweralkylsulfonyl; 
     R 1 , R 2  and R 3  are hydrogen or loweralkyl; 
     R&#39; and R&#34; are hydrogen, 
     loweralkyl, 
     intermediate alkyl, 
     loweralkenyl, 
     cycloalkyl, 
     cycloalkylloweralkyl, 
     aralkyl, 
     cycloalkenyl or 
     R&#39; and R&#34; together are loweralkylidenyl or heteroloweralkylidenyl, provided R 1 , R 2 , R 3 , R&#39; and R&#34; are not all hydrogen at the same time; and 
     the non-toxic acid addition salts thereof. 
     Compounds of this invention which are preferred are described by general formula I 
     where: 
     X is hydrogen or 
     loweralkyl, 
     halo; 
     Y is hydrogen, 
     halo, 
     loweralkyl or 
     haloloweralkyl; and 
     Z is halo, 
     loweralkyl or 
     loweralkoxy, 
     nitro, 
     haloloweralkyl; 
     R 1 , R 2  and R 3  are hydrogen or loweralkyl; and 
     R&#39; and R&#34; are hydrogen, 
     loweralkyl or 
     cycloalkyl; 
     provided R 1 , R 2 , R&#39; and R&#34; are not all hydrogen at the same time. 
     The more preferred compounds of this invention include those compounds where: 
     X is hydrogen, 
     methyl, 
     ethyl, 
     propyl, 
     i-propyl, 
     butyl, 
     chloro, 
     bromo or 
     fluoro; 
     Y is hydrogen, 
     chloro, 
     bromo, 
     fluoro, 
     methyl, 
     ethyl, 
     propyl, 
     i-propyl, 
     butyl, 
     trifluoromethyl; and 
     Z is chloro, 
     bromo, 
     fluoro, 
     methyl, 
     ethyl, 
     propyl, 
     i-propyl, 
     butyl, 
     methoxy, 
     ethoxy, 
     nitro or 
     trifluoromethyl; 
     R 1 , R 2  and R 3  are hydrogen, 
     methyl or 
     ethyl; 
     R&#39; and R&#34; are hydrogen, 
     methyl, 
     ethyl, 
     propyl, 
     i-propyl, 
     butyl, 
     t-butyl, 
     cyclopropyl, 
     cyclobutyl, 
     cyclopentyl or 
     cyclohexyl; 
     provided R 1 , R 2 , R 3 , R&#39; and R&#34; are not all hydrogen at the same time. 
     The most preferred compounds of this invention are described where: 
     X is hydrogen, 
     chloro, 
     bromo, 
     fluoro, 
     methyl or 
     ethyl; 
     Y is hydrogen, 
     chloro, 
     bromo, 
     fluoro, 
     methyl, 
     ethyl or 
     trifluoromethyl; 
     Z is chloro, 
     bromo, 
     fluoro, 
     methyl, 
     ethyl or 
     trifluoromethyl; 
     R 1 , R 2  and R 3  are hydrogen or 
     methyl; and 
     R&#39; and R&#34; are hydrogen, 
     methyl, 
     ethyl, 
     propyl, 
     i-propyl, 
     butyl or 
     t-butyl; 
     provided R 1 , R 2 , R 3 , R&#39; and R&#34; are not all hydrogen at the same time. 
     A special embodiment of this invention is described where X is hydrogen, Y is 2-chloro and Z is 6-chloro. 
     Another special embodiment is described where X and Y are hydrogen and Z is 4-fluoro. 
     A further special embodiment is described where X is 2-methyl or 2-ethyl; Y is hydrogen; and Z is in the 6-position and is chloro, bromo, fluoro, methyl or ethyl. 
     Another special embodiment is described where X is in the 6-position and is chloro, bromo or fluoro; Y is in the 4-position and is methyl, ethyl, chloro, bromo or fluoro; and Z is in the 2-position and is chloro, bromo or fluoro. 
     A further embodiment is described where X is 2-methyl or 2-ethyl; Y is in the 4-position and is methyl, ethyl, chloro, bromo or fluoro; and Z is in the 6 -position and is methyl, ethyl, chloro, bromo or fluoro. 
     In the descriptive portions of this invention, the following definitions apply: 
     The nomenclature applied to the compounds of this invention ##STR2## 
     The term &#34;loweralkyl&#34; refers to an alkyl hydrocarbon group contianing from 1 to 5 carbon atoms which may be straight chained or branched. 
     The term &#34;intermediate alkyl&#34; refers to an alkyl hydrocarbon group containing from 6 to 12 carbon atoms which may be straight chained or branched. 
     The &#34;acyl&#34; radical may be any organic radical derived from an organic acid by its removal of the hydroxy group such as benzoyl, toluyl, etc. 
     The &#34;loweralkoxy&#34; radical signifies an alkoxy group containing from 1 to about 6 carbon atoms which can be straight chained or branched. 
     The &#34;loweralkenyl&#34; group refers to an alkenyl hydrocarbon group containing from 2 to about 6 carbon atoms which may be straight chained or branched. 
     &#34;Cycloalkyl&#34; refers to a cycloalkyl hydrocarbon ring having from 3 to 8 carbon atoms. 
     &#34;Cycloalkenyl&#34; refers to a cycloalkenyl hydrocarbon ring having from 3 to 8 carbon atoms. 
     The &#34;loweralkylidenyl&#34; radical refers to an alkylidene hydrocarbon radical containing from 2 to 8 carbon atoms thus forming a ring. 
     The &#34;heteroloweralkylidenyl&#34; radical refers to an alkylidene hydrocarbon radical containing from 2 to 8 carbon atoms and one or more hetero atoms selected from oxygen, nitrogen and sulfur, thus forming a hetero ring. 
     &#34;Aryl&#34; refers to an aromatic ring preferably phenyl. 
     This invention further describes a new method for treatment of cardiovascular disorders by the administration of a therapeutically effective amount of an amidinourea compound of formula II ##STR3## where: R 2 , R 3 , R 4 , R 5  and R 6  may be the same or different and are 
     hydrogen, 
     halo, 
     haloloweralkyl, 
     nitro, 
     cyano, 
     loweralkylsulfonyl, 
     loweralkoxy or 
     loweralkyl; 
     R 1 , R 2  and R 3  are hydrogen or 
     loweralkyl; 
     R&#39; and R&#34; are hydrogen, 
     loweralkyl, 
     intermediate alkyl, 
     loweralkenyl, 
     cycloalkyl, 
     cycloalkylloweralkyl, 
     aralkyl, 
     cycloalkenyl or 
     aryl; 
     R&#39; and R&#34; together are loweralkylidenyl or 
     heteroloweralkylidenyl; 
     provided R 1 , R 2 , R 3 , R&#39; and R&#34; are not all hydrogen at the same time; and the non-toxic acid addition salts thereof. 
     The preferred compounds which are useful in the treatment of cardiovascular disorders are exemplified by those compounds of formula III ##STR4## where: X&#39;, Y&#39; and Z&#39; may be the same or different and are 
     hydrogen, provided at least one of X&#39;, Y&#39; and Z&#39; is other than hydrogen, 
     halo, 
     haloloweralkyl or 
     loweralkyl; 
     R 1 , R 2  and R 3  are hydrogen or 
     loweralkyl; and 
     R&#39; and R&#34; are hydrogen, 
     loweralkyl or 
     cycloalkyl; 
     provided R 1 , R 2 , R 3 , R&#39; and R&#34; are not all hydrogen at the same time. 
     The more preferred compounds which are useful in the treatment of cardiovascular disorders are shown in formula III where: 
     X&#39;, Y&#39; and Z&#39; are 
     hydrogen, provided at least one of X&#39;, Y&#39; and Z&#39; is other than hydrogen, 
     halo, 
     haloloweralkyl or 
     loweralkyl; 
     R 1 , R 2  and R 3  are hydrogen or 
     methyl; 
     R&#39; is hydrogen; and 
     R&#34; is hydrogen, 
     methyl, 
     ethyl, 
     propyl, 
     i-propyl, 
     butyl, 
     t-butyl, 
     cyclopropyl, 
     cyclobutyl, 
     cyclopentyl or 
     cyclohexyl; 
     provided R 1 , R 2 , R 3 , R&#39; and R&#34; are not all hydrogen at the same time. 
     The most preferred compounds are described by formula III where: 
     X&#39; is hydrogen, 
     chloro, 
     bromo, 
     fluoro, 
     methyl or 
     ethyl; 
     Y&#39; is hydrogen, 
     chloro, 
     bromo, 
     fluoro, 
     methyl, 
     ethyl or 
     trifluoromethyl; 
     Z&#39; is chloro, 
     bromo, 
     fluoro, 
     methyl, 
     ethyl or 
     trifluoromethyl; 
     R 1 , R 2  and R 3  are hydrogen or 
     methyl; 
     R&#39; is hydrogen; and 
     R&#34; is hydrogen, 
     methyl, 
     ethyl, 
     propyl, 
     i-propyl, 
     butyl or 
     t-butyl; 
     provided R 1 , R 2 , R 3 , R&#39; and R&#34; are not all hydrogen at the same time. 
     A special embodiment of this invention is described where X is hydrogen, Y is 2-chloro and Z is 6-chloro. 
     Another special embodiment is described where X and Y are hydrogen and Z is fluoro. 
     A further special embodiment is described where X is 2-methyl or 2-ethyl; Y is hydrogen; and Z is in the 6-position and is chloro, bromo, fluoro, methyl or ethyl. 
     Another special embodiment is described where X is in the 6-position and is chloro, bromo or fluoro; Y is in the 4-position and is methyl, ethyl, bromo or fluoro; and Z is in the 2-position and is chloro, bromo or fluoro. 
     A further embodiment is described where X is 2-methyl or 2-ethyl; Y is in the 4-position and is methyl, ethyl, chloro, bromo or fluoro; and Z is in the 6-position and is methyl, ethyl, chloro, bromo or fluoro. 
     It is well known in the pharmacological arts that non-toxic acid addition salts of pharmacologically active amine compounds do not differ in activities from their free base. The salts merely provide a convenient solubility factor. 
     The amines of this invention may be readily converted to their non-toxic acid addition salts by customary methods in the art. The nontoxic salts of this invention are those salts the acid component of which is pharmacologically acceptable in the intended dosages; such salts would include those prepared from inorganic acids, organic acids, higher fatty acids, high molecular weight acids, etc., and include such as: 
     
         ______________________________________                                    
hydrochloric acid,   succinic acid,                                       
hydrobromic acid,    glycolic acid,                                       
sulfuric acid,       lactic acid,                                         
nitric acid,         salicylic acid,                                      
phosphoric acid,     benzoic acid,                                        
methanesulfonic acid,                                                     
                     nicotinic acid,                                      
benzenesulfonic acid,                                                     
                     phthalic acid,                                       
acetic acid,         stearic acid,                                        
propionic acid,      oleic acid,                                          
malic acid,          abietic acid, etc.                                   
______________________________________                                    
 
    
     Representative compounds of this invention which are particularly useful are as follows: 
     1-(2,6-dichlorophenylamidino)-3-(t-butyl)urea 
     1-(p-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dichlorophenylamidino)-3-(t-butyl)urea 
     1-(2,4,6-trichlorophenylamidino)-3-(t-butyl)urea 
     1-(p-bromophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dibromophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-fluoro-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-fluoro-6-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(p-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-difluorophenylamidino)-3-(t-butyl)urea 
     1-(2,6-difluorophenylamidino)-3-(t-butyl)urea 
     1-(p-trifluoromethylphenylamidino)-3-(t-butyl)urea 
     1-(p-trifluoromethoxyphenylamidino)-3-(t-butyl)urea 
     1-(p-methylsulfonylphenylamidino)-3-(t-butyl)urea 
     1-(p-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-bromo-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-fluoro-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-cyanophenylamidino)-3-(t-butyl)urea 
     1-(2-methyl-4-chlorophenylamidino)-3(t-butyl)urea 
     1-(2-methyl-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-methyl-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-methylphenylamidino)-3-(t-butyl)urea 
     1-(2-fluoro-4-methylphenylamidino)-3-(t-butyl)urea 
     1-(2-methyl-6-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-methyl-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dimethylphenylamidino)-3-(t-butyl)urea 
     1-(2,6-dimethylphenylamidino)-3-(t-butyl)urea 
     1-(4-trifluoromethyl-2-chlorophenylamidino)-3-(t-butyl)urea 
     1-(4-trifluoromethyl-2-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dichloro-6-methylphenylamidino)-3-(t-butyl)urea 
     1-(2,6-dichloro-4-methylphenylamidino)-3-(t-butyl)urea 
     1-(3,5-ditrifluoromethylphenylamidino)-3-(t-butyl)urea 
     1-(2-trifluoromethyl-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dimethyl-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dimethyl-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dimethyl-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dimethyl-4-trifluoromethylphenylamidino)-3-(t-butyl)urea 
     1-(2-ethyl-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dichloro-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-methyl-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dimethyl-6-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dimethyl-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-fluoro-6-methylphenylamidino)-3-(t-butyl)urea 
     1-(2,6-dichloro-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-bromo-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dichlorophenyl-N-methylamidino)urea 
     1-(2,6-dichlorophenyl-N-methylamidino)-3-(t-butyl)urea 
     1-(2,6-dichlorophenylamidino)-1-methylurea 
     1-(2,6-dichlorophenyl-N-methylamidino)-1-methylurea 
     1-(2,6-dichlorophenyl-N-methylamidino)urea 
     1-(2,6-dichlorophenylamidino)-3,3-(α,α&#39;-dimethylpentamethylene)urea 
     1-(2,6-dichlorophenyl-N&#39;-methylamidino)-3,3-diethylurea 
     The compounds of this invention exert activity on the cardiovascular system. They possess blood-pressure lowering effects and are useful as antihypertensive agents. 
     For these purposes, the amidinoureas of this invention can be normally administered orally or parenterally. Orally they may be administered as tablets, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. 
     Compositions intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents seleced from the group consisting of sweetening agents, flavoring agents, coloring agents, preserving agents and the like, in order to provide a pharmaceutically elegant and palatable preparation. 
     The dosage regimen in carrying out the methods of this invention is that which insures maximum therapeutic response until improvement is obtained and thereafter the minimum effective level which gives relief. Thus, in general, the dosages are those that are therapeutically effective in the alleviation of hypertensive disorders. In general, the daily dose can be between about 0.05 mg/kg/day and 70 mg/kg/day (preferably in the range of 1-25 mg/kg/day), bearing in mind, of course, that in selecting the appropriate dosage in any specific case, consideration must be given to the patient&#39;s weight, general health, age, and other factors which may influence response to the drug. 
     Various tests in animals have been carried out to show the ability of the compounds of this invention to exhibit reactions that can be correlated with activity in humans. 
     One such test is the ability of the compound to lower blood pressure in the spontaneous hypertensive rat (Ryo Tabei, et al., Clin. Pharm. &amp; Therap. 11: 269-274, 1970). Blood pressure measurements are recorded by both the tail cuff method and by direct cannulation of a common carotid artery. Compounds that are effective antihypertensives in man have been shown to be active in lowering blood pressure in this animal model. In view of the results of this rest, the amidinoureas of this invention can be considered to be active antihypertensive agents. 
     The compounds of this invention may be prepared by the following general synthesis: 
     Condensation of cyanamide and a substituted aniline results in the corresponding substituted phenylguanidine. 
     The reaction is preferably carried out on the aniline salt either in a polar medium or neat and using increased temperatures. The salt used may be any acid addition amine salt but preferably the salt of a mineral acid. The polar medium may be aqueous, partially aqueous or a non-aqueous solution. It is convenient to choose a solvent that will reflux at the desired reaction temperature. The more preferred solvents are water or alcohol but other solvents may be used such as DMSO, diethyleneglycol, ethyleneglycol, tetrahydrofuran, dimethylformamide, etc. The most preferred solvent is a mildly acidic solvent which is non-nucleophilic such as phenol, cresol, xylenol, etc. The reaction should also be carried out at a temperature which is high enough so that condensation takes place readily, but not sufficient to decompose the guanidine formed. The reaction temperature can vary from room temperature to about 250° C. although it is preferable to run the reaction at temperatures from about 50° C. to 150° C. The guanidine salt which is formed can be converted to the free base with a metal hydroxide or alkoxide solution. The isolation of the desired guanidine can be carried out by any method known in the art. 
     When the substituted phenylguanidine is reacted with a substituted isocyanate of the formula R&#39;NCO, then the product formed is a 1-substituted phenylamidino-3-R&#39; urea. This reaction is preferably carried out in a non-polar medium using solvents such as benzene, toluene, xylene, etc. The reaction is also carried out as above at raised temperatures. 
     The following reaction equations illustrate this synthesis: ##STR5## where HX&#39; is a mineral acid and R&#39; is other than hydrogen. 
     When R 1  substitution is desired, it is convenient to carry out the condensation using the appropriately N-substituted aniline. Thus, for example, N-methyl-2,6-dichloroaniline would result in the 1-(2,6-dichlorophenyl)-1-methylguanidine. This is then reacted as above with the isocyanate to form the amidinourea. ##STR6## 
     It is convenient to use t-butylisocyanate in the above reaction when R 3  is not desired. This may then be selectively hydrolyzed off. 
     When R 3  substitution is desired, it is convenient to carry out the condensation using the appropriately substituted cyanamide of the formula NHNHR 3 . Thus, for example, methylcyanamide condensed with 2,6-dichloroaniline would result in the corresponding 1-(2,6-dichlorophenyl)-3-ethylguanidine. This is then reacted as above with the isocyanate to form the amidinoureas. ##STR7## 
     Condensation of an aniline with benzoylthiourea results in the 1-substitutedphenyl-3-benzoylthiourea. This may then be hydrolyzed to the 1-substitutedphenylthiourea and treated with iodomethane to obtain the 1-substitutedphenyl-2-methyl-pseudothiouronium iodide. When the latter is treated with an amine of the formula NH 2  R 1 , the resultant displacement yields a 1-substitutedphenyl-3-R 1  guanidine which may then be reacted as above to form the amidinourea. ##STR8## 
     These compounds may also be prepared by condensing the desired aniline with a substituted isothiourea or with a thiocyanate of the formula SCNR 3 . The latter reaction product is the thiourea which is then treated with iodomethane and reacted with an amine of the formula NH 2  R 2  to obtain the desired guanidine. The above guanidine compounds are reacted with an isocyanate as above to obtain the amidinourea. ##STR9## 
     When R 2  substitution is desired the aniline is condensed with t-butyl thiocyanate of the formula SCN-t-butyl to form the thiourea. The t-butyl group is then hydrolyzed off with conc. HCl. The product is reacted with an isocyanate to obtain the carbamylthiourea, which is treated with iodomethane and reacted with an amine of the formula NHR 2  to obtain the desired amidinourea. ##STR10## 
     When R&#39; and R&#34; substitution is desired the appropriate guanidine is reacted with the acid chloride of the amine of the formula ##STR11## The latter is made by the reaction of the amine of the formula ##STR12## with phosgene in an inert solvent. The reaction of the acid chloride and guanidine is carried out in a polar medium and inert conditions at moderate temperatures. ##STR13## 
     Appropriately desired end products having various X, Y and Z substituents may be prepared at various steps of synthesis using suitable reactions in order to convert one group to another. 
     The starting anilines are either known, may be prepared by known techniques or reference to the preparation is shown. Thus, chlorination or bromination of an acetanilide or aniline may be carried out in acetic acid, or in the presence of a small amount of iodine dissolved in an inert solvent such as carbon tetrachloride. A solution of chlorine or bromine is then added while the temperature is held near 0° C. Iodination may also be carried out by known methods using iodine monochloride (ClI). 
     Alkylation may be carried out on an acetanilide using an alkyl halide and aluminum chloride under Friedel-Crafts conditions to obtain desired alkyl substitution. 
     Nitration may be carried out using fuming nitric acid at about 0° C. 
     A nitro compound may be hydrogenated to the corresponding amine which may then be diazotized and heated in an alcohol medium to form the alkoxy compound. 
     An amino compound may also be diazotized to the diazonium fluoroborate which is then thermally decomposed to the fluoro compound. Diazotization followed by a Sandmeyer type reaction may yield the bromo, chloro or iodo compound. 
     Diazotization of an amino compound followed by addition of cuprous cyanide may result in the desired cyano compound. 
     When an amino compound is diazotized followed by reaction with potassium ethylxanthate and then hydrolyzed, the mercapto compound results. This in turn may be alkylated to the alkylthio group which is then oxidized to the corresponding alkylsulfonyl substituent. 
     A halo compound in which halo is chloro or bromo or iodo may be reacted with cuprous cyanide in guanidine at about 150° C. to produce a cyano compound. 
     A chloro, bromo or iodo compound may also be reacted with trifluoromethyliodide and copper powder at about 150° C. in dimethylformamide to obtain a trifluoromethyl compound [Tetrahedron Letters: 47, 4095 (1959)]. 
     A halo compound may also be reacted with cuprous methanesulfinate in quinoline at about 150° C. to obtain a methylsulfonyl compound. 
     Of course the above reaction may also be carried out on acetophenone in order to direct substitution. Formation of an oxime followed by Beckmann Rearrangement results in the acetamide which is then deacylated to the aniline. 
     Reactions may also be carried out on the substituted anilines which would result in di- and tri- substituted anilines. 
     Reactions may also be carried out at other stages of synthesis depending on the substituents present and the substituents desired and various combinations of the foregoing reactions will be determined by one skilled in the art in order that the desired product results. Thus, a phenylguanidine or amidinourea may be halogenated or nitrated as above, etc. 
    
    
     The following are detailed examples which show the preparation of the compounds of this invention. They are to be construed as illustrations of said compounds and not as limitations thereof. 
     EXAMPLE 1 
     2,6-Dichlorophenylguanidine 
     To 51 g (0.315 mole) of 2,6-dichloroaniline is added 0.4 moles of ethereal HCl and 200 ml of m-cresol. The mixture is then stirred and heated on a steam bath to drive off the ether and excess hydrogen chloride. To the resultant mixture is then added 13.3 g (0.315 mole) of cyanamide then heated for 2 hours on a steam bath. The reaction mixture is then cooled, added to 150 ml of conc. sodium hydroxide solution, cooled and extracted with 2 liters of ether. The ether layer is washed with 2×1 liter of water, dried over sodium sulfate, charcoaled and evaporated. The residue is triturated with hexane and the precipitate is filtered off and washed with ether and dried to obtain 2,6-dichlorophenylguanidine hydrochloride. 
     The free base is prepared by dissolving 2,6-dichlorophenylguanidine hydrochloride in 10% sodium hydroxide solution and extracting with ether. The ether is dried and evaporated to dryness to obtain 2,6-dichlorophenylguanidine. 
     When the above procedures are followed using the amines of Table I, below, then the corresponding product of Table II, below, is prepared. 
     
         __________________________________________________________________________
TABLE I          TABLE II                                                 
__________________________________________________________________________
o-chloroaniline  o-chlorophenylguanidine                                  
m-chloroaniline  m-chlorophenylguanidine                                  
p-chloroaniline  p-chlorophenylguanidine                                  
2,3-dichloroaniline                                                       
                 2,3-dichlorophenylguanidine                              
2,4-dichloroaniline                                                       
                 2,4-dichlorophenylguanidine                              
2,5-dichloroaniline                                                       
                 2,5-dichlorophenylguanidine                              
3,4-dichloroaniline                                                       
                 3,4-dichlorophenylguanidine                              
3,5-dichloroaniline                                                       
                 3,5-dichlorophenylguanidine                              
2,3,4-tirchloroaniline                                                    
                 2,3,4-trichlorophenylguanidine                           
2,3,5-trichloroaniline                                                    
                 2,3,5-trichlorophenylguanidine                           
2,3,6-trichloroaniline                                                    
                 2,3,6-trichlorophenylguanidine                           
2,4,5-trichloroaniline                                                    
                 2,4,5-trichlorophenylguandine                            
2,4,6-trichloroaniline                                                    
                 2,4,6-trichlorophenylguanidine                           
3,4,5-trichloroaniline                                                    
                 3,4,5-trichlorophenylguanidine                           
o-bromoaniline   o-bromophenylguanidine                                   
m-bromoaniline   m-bromophenylguanidine                                   
p-bromoaniline   p-bromophenylguanidine                                   
2,3-dibromoaniline                                                        
                 2,3-dibromophenylguanidine                               
2,4-dibromoaniline                                                        
                 2,4-dibromophenylguanidine                               
2,5-dibromoaniline                                                        
                 2,5-dibromophenylguanidine                               
2,6-dibromoaniline                                                        
                 2,6-dibromophenylguanidine                               
3,4-dibromoaniline                                                        
                 3,4-dibromophenylguanidine                               
3,5-dibromoaniline                                                        
                 3,5-dibromophenylguanidine                               
2-chloro-3-bromoaniline                                                   
                 2-chloro-3-bromophenylguanidine                          
2-chloro-4-bromoaniline                                                   
                 2-chloro-4-bromophenylguanidine                          
2-chloro-5-bromoaniline                                                   
                 2-chloro-5-bromophenylguanidine                          
2-chloro-6-bromoaniline                                                   
                 2-chloro-6-bromophenylguanidine                          
3-chloro-2-bromoaniline                                                   
                 3-chloro-2-bromophenylguanidine                          
3-chloro-4-bromoaniline                                                   
                 3-chloro-4-bromophenylguanidine                          
3-chloro-5-bromoaniline                                                   
                 3-chloro-5-bromophenylguanidine                          
3-chloro-6-bromoaniline                                                   
                 3-chloro-6-bromophenylguanidine                          
4-chloro-2-bromoaniline                                                   
                 4-chloro-2-bromophenylguanidine                          
4-chloro-3-bromoaniline                                                   
                 4-chloro-3-bromophenylguanidine                          
2-fluoro-4-chloroaniline                                                  
                 2-fluoro-4-chlorophenylguanidine                         
2-fluoro-6-chloroaniline                                                  
                 2-fluoro-6-chlorophenylguanidine                         
2-chloro-4-bromoaniline                                                   
                 2-chloro-4-fluorophenylguanidine                         
2-fluoro-6-bromoaniline                                                   
                 2-fluoro-6-bromophenylguanidine                          
2-bromo-4-fluoroaniline                                                   
                 2-bromo-4-fluorophenylguanidine                          
2-iodo-4-chloroaniline                                                    
                 2-iodo-4-chlorophenylguanidine                           
2-iodo-6-chloroaniline                                                    
                 2-iodo-6-chlorophenylguanidine                           
2-chloro-4-iodoaniline                                                    
                 2-chloro-4-iodophenylguanidine                           
2-iodo-4-bromoaniline                                                     
                 2-iodo-4-bromophenylguanidine                            
o-fluoroaniline  o-fluorophenylguanidine                                  
m-fluoroaniline  m-fluorophenylguanidine                                  
p-fluoroaniline  p-fluorophenylguanidine                                  
p-iodoaniline    p-iodophenylguanidine                                    
2,4-difluoroaniline                                                       
                 2,4-difluorophenylguanidine                              
2,5-difluoroaniline                                                       
                 2,5-difluorophenylguanidine                              
2,6-difluoroaniline                                                       
                 2,6-difluorophenylguanidine                              
2,4-diiodoaniline                                                         
                 2,4-diiodophenylguanidine                                
2-iodo-6-bromoaniline                                                     
                 2-iodo-6-bromophenylguanidine                            
2-bromo-4-iodoaniline                                                     
                 2-bromo-4-iodophenylguanidine                            
2-fluoro-4-iodoaniline                                                    
                 2-fluoro-4-iodophenylguanidine                           
2-iodo-4-fluoroaniline                                                    
                 2-iodo-4-fluorophenylguanidine                           
o-trifluoromethylaniline                                                  
                 o-trifluoromethylphenylguanidine                         
m-trifluoromethylaniline                                                  
                 m-trifluoromethylphenylguanidine                         
p-trifluoromethylaniline                                                  
                 p-trifluoromethylphenylguanidine                         
p-trifluoromethoxyaniline                                                 
                 p-trifluoromethoxyphenylguanidine                        
p-methylsulfonylaniline                                                   
                 p-methylsulfonylphenylguanidine                          
o-nitroaniline   o-nitrophenylguanidine                                   
m-nitroaniline   m-nitrophenylguanidine                                   
p-nitroaniline   p-nitrophenylguanidine                                   
2-chloro-4-nitroaniline                                                   
                 2-chloro-4-nitrophenylguanidine                          
2-bromo-4-nitroaniline                                                    
                 2-bromo-4-nitrophenylguanidine                           
2-iodo-4-nitroaniline                                                     
                 2-iodo-4-nitrophenylguanidine                            
2-fluoro-4-nitroaniline                                                   
                 2-fluoro-4-nitrophenylguanidine                          
2-nitro-4-chloroaniline                                                   
                 2-nitro-4-chlorophenylguanidine                          
2-nitro-4-bromoaniline                                                    
                 2-nitro-4-bromophenylguanidine                           
2-nitro-4-fluoroaniline                                                   
                 2-nitro-4-fluorophenylguanidine                          
2-nitro-4-trifluoromethylaniline                                          
                 2-nitro-4-trifluoromethylphenylguanidine                 
2-nitro-4-methoxyaniline                                                  
                 2-nitro-4-methoxyphenylguanidine                         
2-cyano-4-chloroaniline                                                   
                 2-cyano-4-chlorophenylguanidine                          
2-chloro-4-cyanoaniline                                                   
                 2-chloro-4-cyanophenylguanidine                          
2-methyl-4-chloroaniline                                                  
                 2-methyl-4-chlorophenylguanidine                         
2-methyl-4-bromoaniline                                                   
                 2-methyl-4-bromophenylguanidine                          
2-methyl-4-fluoroaniline                                                  
                 2-methyl-4-fluorophenylguanidine                         
2-chloro-4-methylaniline                                                  
                 2-chloro-4-methylphenylguanidine                         
2-bromo-4-methylaniline                                                   
                 2-bromo-4-methylphenylguanidine                          
2-fluoro-4-methylaniline                                                  
                 2-fluoro-4-methylphenylguanidine                         
2-cyano-4-methylaniline                                                   
                 2-cyano-4-methylphenylguanidine                          
2-trifluoromethyl-4-methylaniline                                         
                 2-trifluoromethyl-4-methylphenylguanidine                
2-methyl-4-nitroaniline                                                   
                 2-methyl-4-nitrophenylguanidine                          
2-methyl-4-cyanoaniline                                                   
                 2-methyl-4-cyanophenylguanidine                          
2-methyl-4-trifluoromethylaniline                                         
                 2-methyl-4-trifluoromethylphenylguanidine                
2-chloro-6-nitroaniline                                                   
                 2-chloro-6-nitrophenylguanidine                          
2-bromo-6-nitroaniline                                                    
                 2-bromo-6-nitrophenylguanidine                           
2-iodo-6-nitroaniline                                                     
                 2-iodo-6-nitrophenylguanidine                            
2-fluoro-6-nitroaniline                                                   
                 2-fluoro-6-nitrophenylguanidine                          
2-nitro-6-trifluoromethylaniline                                          
                 2-nitro-6-trifluoromethylphenylguanidine                 
2-nitro-6-methyoxyaniline                                                 
                 2-nitro-6-methoxyphenylguanidine                         
2-cyano-6-chloroaniline                                                   
                 2-cyano-6-chlorophenylguanidine                          
2-methyl-6-chloroaniline                                                  
                 2-methyl-6-chlorophenylguanidine                         
2-methyl-6-bromoaniline                                                   
                 2-methyl-6-bromophenylguanidine                          
2-methyl-6-fluoroaniline                                                  
                 2-methyl-6-fluorophenylguanidine                         
2-methyl-6-nitroaniline                                                   
                 2-methyl-6-nitrophenylguanidine                          
2-methyl-6-trifluoromethylaniline                                         
                 2-methyl-6-trifluoromethylphenylguanidine                
2-methyl-6-cyanoaniline                                                   
                 2-methyl-6-cyanophenylguanidine                          
2-methyl-6-methylsulfonylaniline                                          
                 2-methyl-6-methylsulfonylphenylguanidine                 
2,4-dimethylaniline                                                       
                 2,4-dimethylphenylguanidine                              
2,6-dimethylaniline                                                       
                 2,6-dimethylphenylguanidine                              
2-trifluoromethyl-6-chloroaniline                                         
                 2-trifluoromethyl-6-chlorophenylguanidine                
2-trifluoromethyl-6-bromoaniline                                          
                 2-trifluoromethyl-6-bromophenylguanidine                 
2-trifluoromethyl-6-fluoroaniline                                         
                 2-trifluoromethyl-6-fluorophenylguanidine                
2-trifluoromethyl-6-nitroaniline                                          
                 2-trifluoromethyl-6-nitrophenylguanidine                 
2-trifluoromethyl-4-chloroaniline                                         
                 2-trifluoromethyl-4-chlorophenylguanidine                
2-trifluoromethyl-4-bromoaniline                                          
                 2-trifluoromethyl-4-bromophenylguanidine                 
2-trifluoromethyl-4-fluoroaniline                                         
                 2-trifluoromethyl-4-fluorophenylguanidine                
4-trifluoromethyl-2-chloroaniline                                         
                 4-trifluoromethyl-2-chlorophenylguanidine                
4-trifluoromethyl-2-bromoaniline                                          
                 4-trifluoromethyl-2-bromophenylguanidine                 
4-trifluoromethyl-2-fluoroaniline                                         
                 4-trifluoromethyl-2-bromophenylguanidine                 
2,4-dichloro-6-methylaniline                                              
                 2,4-dichloro-6-methylphenylguanidine                     
2,6-dichloro-4-methylaniline                                              
                 2,6-dichloro-4-methylphenylguanidine                     
3,5-ditrifluoromethylaniline                                              
                 3,5-ditrifluoromethylphenylguanidine                     
2-methoxy-4-nitroaniline                                                  
                 2-methoxy-4-nitrophenylguanidine                         
2-trifluoromethyl-4-nitroaniline                                          
                 2-trifluoromethyl-4-nitrophenylguanidine                 
2,4-dichloro-6-methoxyaniline                                             
                 2,4-dichloro-6-methoxyphenylguanidine                    
2,6-dimethyl-4-chloroaniline                                              
                 2,6-dimethyl-4-chlorophenylguanidine                     
2,6-dimethyl-4-fluoroaniline                                              
                 2,6-dimethyl-4-fluorophenylguanidine                     
2,6-dimethyl-4-bromoaniline                                               
                 2,6-dimethyl-4-bromophenylguanidine                      
2,6-dimethyl-4-nitroaniline                                               
                 2,6-dimethyl-4-nitrophenylguanidine                      
2,6-dimethyl-4-trifluoromethyl-                                           
                 2,6-dimethyl-4-trifluoromethylphenyl-                    
aniline          guanidine                                                
2-ethyl-4-nitroaniline                                                    
                 2-ethyl-4-nitrophenylguanidine                           
2-ethyl-4-chloroaniline                                                   
                 2-ethyl-4-chlorophenylguanidine                          
2-ethyl-4-bromoaniline                                                    
                 2-ethyl-4-bromophenylguanidine                           
2-ethyl-4-fluoroaniline                                                   
                 2-ethyl-4-fluorophenylguanidine                          
2-ethyl-4-trifluoromethylaniline                                          
                 2-ethyl-4-trifluoromethylphenylguanidine                 
2-ethyl-4-cyanoaniline                                                    
                 2-ethyl-4-cyanophenylguanidine                           
2-ethyl-4-methylsulfonylaniline                                           
                 2-ethyl-4-methylsulfonylphenylguanidine                  
2,4-dichloro-6-bromoaniline                                               
                 2,4-dichloro-6-bromophenylguanidine                      
2,6-dichloro-4-bromoaniline                                               
                 2,6-dichloro-4-bromophenylguanidine                      
2,4-dibromo-6-chloroaniline                                               
                 2,4-dibromo-6-chlorophenylguanidine                      
2,6-dibromo-4-chloroaniline                                               
                 2,6-dibromo-4-chlorophenylguanidine                      
2,4-dichloro-6-fluoroaniline                                              
                 2,4-dichloro-6-fluorophenylguanidine                     
2-chloro-4-methyl-6-fluoroaniline                                         
                 2-chloro-4-methyl-6-fluorophenylguanidine                
2,4-dimethyl-6-chloroaniline                                              
                 2,4-dimethyl-6-chlorophenylguanidine                     
2,4-dimethyl-6-fluoroaniline                                              
                 2,4-dimethyl-6-fluorophenylguanidine                     
2-chloro-4-fluoro-6-methylaniline                                         
                 2-chloro-4-fluoro-6-methylphenylguanidine                
2,6-dichloro-4-fluoroaniline                                              
                 2,6-dichloro-4-fluorophenylguanidine                     
2,5-dichloro-4-fluoroaniline                                              
                 2,5-dichloro-4-fluorophenylguanidine                     
2,4-dichloro-6-iodoaniline                                                
                 2,4-dichloro-6-iodophenylguanidine                       
2,6-dichloro-4-iodoaniline                                                
                 2,6-dichloro-4-iodophenylguanidine                       
2,4-dibromo-6-iodoaniline                                                 
                 2,4-dibromo-6-iodophenylguanidine                        
2,4-dibromo-6-fluoroaniline                                               
                 2,4-dibromo-6-fluorophenylguanidine                      
2,6-dibromo-4-fluoroaniline                                               
                 2,6-dibromo-4-fluorophenylguanidine                      
2-chloro-4-bromo-6-fluoroaniline                                          
                 2-chloro-4-bromo-6-fluorophenylguanidine                 
2-bromo-4-fluoro-6-chloroaniline                                          
                 2-bromo-4-fluoro-6-chlorophenylguanidine                 
2-bromo-4-chloro-6-fluoroaniline                                          
                 2-bromo-4-chloro-6-fluorophenylguanidine                 
2-chloro-4-iodo-6-bromoaniline                                            
                 2-chloro-4-iodo-6-bromophenylguanidine                   
2,4,6-tribromoaniline                                                     
                 2,4,6-tribromophenylguanidine                            
2,4,6-trifluoroaniline                                                    
                 2,4,6-trifluorophenylguanidine                           
__________________________________________________________________________
 
    
     EXAMPLE 2 
     1-(2,6-dichlorophenyl)-1-methylguanidine 
     To 55.4 g (0.315 mole) of N-methyl-2,6-dichloroaniline is added 0.4 moles of ethereal HCl and 200 ml of m-cresol. The mixture is then stirred and heated on a steam bath to drive off the ether and excess hydrogen chloride. To the resultant mixture is then added 13.3 g (0.315 mole) of cyanamide then heated for 2 hours on a steam bath. The reaction mixture is then cooled, added to 150 ml of conc. sodium hydroxide solution, cooled and extracted with 2 liters of ether. The ether layer is washed with 2×1 liter of water, dried over sodium sulfate, charcoaled and evaporated. The residue is triturated with hexane and the precipitate is filtered off and washed with ether and dried to obtain 1-(2,6-dichlorophenyl)-1-methylguanidine hydrochloride. 
     The free base is prepared by dissolving 1-(2,6-dichlorophenyl)-1-methylguanidine hydrochloride in 10% sodium hydroxide solution and extracting with ether. The ether is dried and evaporated to dryness to obtain 1-(2,6-dichlorophenyl)-1-methylguanidine. 
     When the N-methylaniline in the above procedures is replaced by the N-loweralkylanilines of this invention then the corresponding product is obtained. 
     When the above procedures are followed using the representative amines of Table I, below, then the corresponding product of Table II, below, is prepared. 
     
         __________________________________________________________________________
TABLE I           TABLE II                                                
__________________________________________________________________________
N-methyl-p-chloroaniline                                                  
                  1-(p-chlorophenyl)-1-methylguanidine                    
N-methyl-2,3-dichloroaniline                                              
                  1-(2,3-dichlorophenyl)-1-methylguanidine                
N-methyl-2,4-dichloroaniline                                              
                  1-(2,4-dichlorophenyl)-1-methylguanidine                
N-methyl-2,5-dichloroaniline                                              
                  1-(2,5-dichlorophenyl)-1-methylguanidine                
N-methyl-3,4-dichloroaniline                                              
                  1-(3,4-dichlorophenyl)-1-methylguanidine                
N-methyl-3,5-dichloroaniline                                              
                  1-(3,5-dichlorophenyl)-1-methylguanidine                
N-methyl-2,3,4-trichloroaniline                                           
                  1-(2,3,4-trichlorophenyl)-1-methylguanidine             
N-methyl-2,3,5-trichloroaniline                                           
                  1-(2,3,5-trichlorophenyl)-1-methylguanidine             
N-methyl-2,3,6-trichloroaniline                                           
                  1-(2,3,6-trichlorophenyl)-1-methylguanidine             
N-methyl-2,4,5-trichloroaniline                                           
                  1-(2,4,5-trichlorophenyl)-1-methylguanidine             
N-methyl-2,4,6-trichloroaniline                                           
                  1-(2,4,6-trichlorophenyl)-1-methylguanidine             
N-methyl-3,4,5-trichloroaniline                                           
                  1-(3,4,5-trichlorophenyl)-1-methylguanidine             
N-methyl-p-bromoaniline                                                   
                  1-(p-bromophenyl)-1-methylguanidine                     
N-methyl-2,4-dibromoaniline                                               
                  1-(2,4-dibromophenyl)-1-methylguanidine                 
N-methyl-2-chloro-4-bromoaniline                                          
                  1-(2-chloro-4-bromophenyl)-1-methylguanidine            
N-methyl-2-chloro-6-bromoaniline                                          
                  1-(2-chloro-6-bromophenyl)-1-methylguanidine            
N-methyl-3-chloro-4-bromoaniline                                          
                  1-(3-chloro-4-bromophenyl)-1-methylguanidine            
N-methyl-3-chloro-5-bromoaniline                                          
                  1-(3-chloro-5-bromophenyl)-1-methylguanidine            
N-methyl-4-chloro-2-bromoaniline                                          
                  1-(4-chloro-2-bromophenyl)-1-methylguanidine            
N-methyl-2-fluoro-4-chloroaniline                                         
                  1-(2-fluoro-4-chlorophenyl)-1-methylguanidine           
N-methyl-2-fluoro-6-chloroaniline                                         
                  1-(2-fluoro-6-chlorophenyl)-1-methylguanidine           
N-methyl-2-chloro-4-fluoroaniline                                         
                  1-(2-chloro-4-fluorophenyl)-1-methylguanidine           
N-methyl-2-fluoro-6-bromoaniline                                          
                  1-(2-fluoro-6-bromophenyl)-1-methylguanidine            
N-methyl-2-bromo-4-fluoroaniline                                          
                  1-(2-bromo-4-fluorophenyl)-1-methylguanidine            
N-methyl-2-iodo-4-chloroaniline                                           
                  1-(2-iodo-4-chlorophenyl)-1-methylguanidine             
N-methyl-2-iodo-6-chloroaniline                                           
                  1-(2-iodo-6-chlorophenyl)-1-methylguanidine             
N-methyl-2-chloro-4-iodoaniline                                           
                  1-(2-chloro-4-iodophenyl)-1-methylguanidine             
N-methyl-2-iodo-4-bromoaniline                                            
                  1-(2-iodo-4-bromophenyl)-1-methylguanidine              
N-methyl-o-fluoroaniline                                                  
                  1-(o-fluorophenyl)-1-methylguanidine                    
N-methyl-m-fluoroaniline                                                  
                  1-(m-fluorophenyl)-1-methylguanidine                    
N-methyl-p-fluoroaniline                                                  
                  1-(p-fluorophenyl)-1-methylguanidine                    
N-methyl-p-iodoaniline                                                    
                  1-(p-iodophenyl)-1-methylguanidine                      
N-methyl-2,4-difluoroaniline                                              
                  1-(2,4-difluorophenyl)-1-methylguanidine                
N-methyl-2,6-difluoroaniline                                              
                  1-(2,6-difluorophenyl)-1-methylguanidine                
N-methyl-2-fluoro-4-iodoaniline                                           
                  1-(2-fluoro-4-iodophenyl)-1-methylguanidine             
N-methyl-o-trifluoromethylaniline                                         
                  1-(o-trifluoromethylphenyl)-1-methylguanidine           
N-methyl-m-trifluoromethylaniline                                         
                  1-(m-trifluoromethylphenyl)-1-methylguanidine           
N-methyl-p-trifluoromethylaniline                                         
                  1-(p-trifluorophenyl)-1-methyl-                         
                  guanidine                                               
N-methyl-p-trifluoromethoxyaniline                                        
                  1-(p-trifluoromethoxyphenyl)-1-methyl-                  
                  guanidine                                               
N-methyl-p-methylsulfonylaniline                                          
                  1-(p-methylsulfonylphenyl)-1-methyl-                    
                  guanidine                                               
N-methyl-p-nitroaniline                                                   
                  1-(p-nitrophenyl)-1-methylguanidine                     
N-methyl-2-chloro-4-nitroaniline                                          
                  1-(2-chloro-4-nitrophenyl)-1-methyl-                    
                  guanidine                                               
N-methyl-2-bromo-4-nitroaniline                                           
                  1-(2-bromo-4-nitrophenyl)-1-methylguanidine             
N-methyl-2-nitro-4-chloroaniline                                          
                  1-(2-nitro-4-chlorophenyl)-1-methylguanidine            
N-methyl-2-nitro-4-bromoaniline                                           
                  1-(2-nitro-4-bromophenyl)-1-methylguanidine             
N-methyl-2-nitro-4-fluoroaniline                                          
                  1-(2-nitro-4-fluorophenyl)-1-methylguanidine            
N-methyl-2-nitro-4-trifluoromethyl-                                       
                  1-(2-nitro-4-trifluoromethylphenyl)-1-                  
aniline           methylguanidine                                         
N-methyl-2-nitro-4-methoxyaniline                                         
                  1-(2-nitro-4-methoxyphenyl)-1-methylguanidine           
N-methyl-2-methyl-4-chloroaniline                                         
                  1-(2-methyl-4-chlorophenyl)-1-methylguanidine           
N-methyl-2-methyl-4-bromoaniline                                          
                  1-(2-methyl-4-bromophenyl)-1-methylguanidine            
N-methyl-2-methyl-4-fluoroaniline                                         
                  1-(2-methyl-4-fluorophenyl)-1-methyl-                   
                  guanidine                                               
N-methyl-2-chloro-4-methylaniline                                         
                  1-(2-methyl-4-fluorophenyl)-1-methyl-                   
                  guanidine                                               
N-methyl-2-bromo-4-methylaniline                                          
                  1-(2-bromo-4-methylphenyl)-1-methyl-                    
                  guanidine                                               
N-methyl-2-fluoro-4-methylaniline                                         
                  1-(2-fluoro-4-methylphenyl)-1-methyl-                   
                  guanidine                                               
N-methyl-2-cyano-4-methylaniline                                          
                  1-(2-cyano-4-methylphenyl)-1-methyl-                    
                  guanidine                                               
N-methyl-2-trifluoromethyl-4-                                             
                  1-(2-trifluoromethyl-4-methylphenyl)-1-                 
methylaniline     methylguanidine                                         
N-methyl-2-methyl-4-nitroaniline                                          
                  1-(2-methyl-4-nitrophenyl)-1-methylguanidine            
N-methyl-2-methyl-4-cyanoaniline                                          
                  1-(2-methyl-4-cyanophenyl)-1-methylguanidine            
N-methyl-2-methyl-4-trifluoro-                                            
                  1-(2-methyl-4-trifluoromethylphenyl)-1-                 
methylaniline     methylguanidine                                         
N-methyl-2-chloro-6-nitroaniline                                          
                  1-(2-chloro-6-nitrophenyl)-1-methylguanidine            
N-methyl-2-bromo-6-nitroaniline                                           
                  1-(2-bromo-6-nitrophenyl)-1-methylguanidine             
N-methyl-2-iodo-6-nitroaniline                                            
                  1-(2-iodo-6-nitrophenyl)-1-methylguanidine              
N-methyl-2-fluoro-6-nitroaniline                                          
                  1-(2-fluoro-6-nitrophenyl)-1-methylguanidine            
N-methyl-2-nitro-6-trifluoro-                                             
                  1-(2-nitro-6-trifluoromethylphenyl)-1-                  
methylaniline     methylguanidine                                         
N-methyl-2-nitro-6-methoxyaniline                                         
                  1-(2-nitro-6-methoxyphenyl)-1-methyl-                   
                  guanidine                                               
N-methyl-2-methyl-6-chloroaniline                                         
                  1-(2-methyl-6-chlorophenyl)-1-methyl-                   
                  guanidine                                               
N-methyl-2-methyl-6-bromoaniline                                          
                  1-(2-methyl-6-bromophenyl)-1-methylguanidine            
N-methyl-2-methyl-6-fluoroaniline                                         
                  1-(2-methyl-6-fluorophenyl)-1-methyl-                   
                  guanidine                                               
N-methyl-2-methyl-6-nitroaniline                                          
                  1-(2-methyl-6-nitrophenyl)-1-methylguanidine            
N-methyl-2-methyl-6-trifluoro-                                            
                  1-(2-methyl-6-trifluoromethylphenyl)-1-                 
methylaniline     methylguanidine                                         
N-methyl-2-methyl-6-cyanoaniline                                          
                  1-(2-methyl-6-cyanophenyl)-1-methylguanidine            
N-methyl-2,4-dimethylaniline                                              
                  1-(2,4-dimethylphenyl)-1-methylguanidine                
N-methyl-2,6-dimethylaniline                                              
                  1-(2,6-dimethylphenyl)-1-methylguanidine                
N-methyl-2-trifluoromethyl-6-                                             
                  1-(2-trifluoromethyl-6-chlorophenyl)-1-                 
chloroaniline     methylguanidine                                         
N-methyl-2-trifluoromethyl-6-                                             
                  1-(2-trifluoromethyl-6-bromophenyl)-1-                  
bromoaniline      methylguanidine                                         
N-methyl-2-trifluoromethyl-6-                                             
                  1-(2-trifluoromethyl-6-fluorophenyl)-1-                 
fluoroaniline     methylguanidine                                         
N-methyl-2-trifluoromethyl-4-                                             
                  1-(2-trifluoromethyl-4-chlorophenyl)-1-                 
chloroaniline     methylguanidine                                         
N-methyl-2-trifluoromethyl-4-                                             
                  1-(2-trifluoromethyl-4-bromophenyl)-1-                  
bromoaniline      methylguanidine                                         
N-methyl-4-trifluoromethyl-2-                                             
                  1-(2-trifluoromethyl-4-fluorophenyl)-1-                 
fluoroaniline     methylguanidine                                         
N-methyl-4-trifluoromethyl-2-                                             
                  1-(4-trifluoromethyl-2-chlorophenyl)-1-                 
chloroaniline     methylguanidine                                         
N-methyl-4-trifluoromethyl-2-                                             
                  1-(4-trifluoromethyl-2-bromophenyl)-1-                  
bromoaniline      methylguanidine                                         
N-methyl-4-trifluoromethyl-2-                                             
                  1-(4-trifluoromethyl-2-fluorophenyl)-1-                 
fluoroaniline     methylguanidine                                         
N-methyl-2,4-dichloro-6-methyl-                                           
                  1-(2,4-dichloro-6-methylphenyl)-1-                      
aniline           methylguanidine                                         
N-methyl-2,6-dichloro-4-methyl-                                           
                  1-(2,6-dichloro-4-methylphenyl)-1-                      
aniline           methylguanidine                                         
N-methyl-3,5-ditrifluoromethyl-                                           
                  1-(3,5-ditrifluoromethylphenyl)-1-                      
aniline           methylguanidine                                         
N-methyl-2-trifluoromethyl-4-                                             
                  1-(2-trifluoromethyl-4-nitrophenyl)-1-                  
nitroaniline      methylguanidine                                         
N-methyl-2,6-dimethyl-4-chloro-                                           
                  1-(2,6-dimethyl-4-chlorophenyl)-1-                      
aniline           methylguanidine                                         
N-methyl-2,6-dimethyl-4-fluoro-                                           
                  1-(2,6-dimethyl-4-fluorophenyl)-1-                      
aniline           methylguanidine                                         
N-methyl-2,6-dimethyl-4-bromo-                                            
                  1-(2,6-dimethyl-4-bromophenyl)-1-                       
aniline           methylguanidine                                         
N-methyl-2,6-dimethyl-4-nitro-                                            
                  1-(2,6-dimethyl-4-nitrophenyl)-1-                       
aniline           methylguanidine                                         
N-methyl-2,6-dimethyl-4-trifluoro-                                        
                  1-(2,6-dimethyl-4-trifluoromethylphenyl)-1-             
methylaniline     methylguanidine                                         
N-methyl-2-ethyl-4-nitroaniline                                           
                  1-(2-ethyl-4-nitrophenyl)-1-methylguanidine             
N-methyl-2-ethyl-4-chloroaniline                                          
                  1-(2-ethyl-4-chlorophenyl)-1-methylguanidine            
N-methyl-2-ethyl-4-bromoaniline                                           
                  1-(2-ethyl-4-bromophenyl)-1-methylguanidine             
N-methyl-2-ethyl-4-fluoroaniline                                          
                  1-(2-ethyl-4-fluorophenyl)-1-methylguanidine            
N-methyl-2-ethyl-4-trifluoro-                                             
                  1-(2-ethyl-4-trifluoromethylphenyl)-1-                  
methylaniline     methylguanidine                                         
N-methyl-2-ethyl-4-cyanoaniline                                           
                  1-(2-ethyl-4-cyanophenyl)-1-methylguanidine             
N-methyl-2-ethyl-4-methylsulfonyl-                                        
                  1-(2-ethyl-4-methylsulfonylphenyl)-1-                   
aniline           methylguanidine                                         
N-methyl-2,4-dichloro-6-bromo-                                            
                  1-(2,4-dichloro-6-bromophenyl)-1-                       
aniline           methylguanidine                                         
N-methyl-2,6-dichloro-4-bromo-                                            
                  1-(2,6-dichloro-4-bromophenyl)-1-                       
aniline           methylguanidine                                         
N-methyl-2,4-dibromo-6-chloro-                                            
                  1-(2,4-dibromo-6-chlorophenyl)-1-                       
aniline           methylguanidine                                         
N-methyl-2,6-dibromo-4-chloro-                                            
                  1-(2,6-dibromo-4-chlorophenyl)-1-                       
aniline           methylguanidine                                         
N-methyl-2,4-dichloro-6-fluoro-                                           
                  1-(2,4-dichloro-6-fluorophenyl)-1-                      
aniline           methylguanidine                                         
N-methyl-2,6-dichloro-4-fluoro-                                           
                  1-(2,6-dichloro-4-fluorophenyl)-1-                      
aniline           methylguanidine                                         
N-methyl-2,6-dichloro-4-fluoro-                                           
                  1-(2,6-dichloro-4-fluorophenyl)-1-                      
aniline           methylguanidine                                         
N-methyl-2,4-dichloro-6-iodo-                                             
                  1-(2,4-dichloro-6-iodophenyl)-1-                        
aniline           methylguanidine                                         
N-methyl-2,6-dichloro-4-iodo-                                             
                  1-(2,6-dichloro-4-iodophenyl)-1-                        
aniline           methylguanidine                                         
N-methyl-2,4-dibromo-6-iodo-                                              
                  1-(2,4-dibromo-6-iodophenyl)-1-                         
aniline           methylguanidine                                         
N-methyl-2,4-dibromo-6-fluoro-                                            
                  1-(2,4-dibromo-6-fluorophenyl)-1-                       
aniline           methylguanidine                                         
N-methyl-2,6-dibromo-4-fluoro-                                            
                  1-(2,6-dibromo-4-fluorophenyl)-1-                       
aniline           methylguanidine                                         
N-methyl-2-chloro-4-bromo-6-                                              
                  1-(2-chloro-4-bromo-6-fluorophenyl)-1-                  
fluoroaniline     methylguanidine                                         
N-methyl-2-bromo-4-fluoro-6-                                              
                  1-(2-bromo-4-fluoro-6-chlorophenyl)-1-                  
chloroaniline     methylguanidine                                         
N-methyl-2-bromo-4-chloro-6-                                              
                  1-(2-bromo-4-chloro-6-fluorophenyl)-1-                  
fluoroaniline     methylguanidine                                         
N-methyl-2-bromo-4-fluoro-6-                                              
                  1-(2-bromo-4-fluoro-6-chlorophenyl)-1-                  
chloroaniline     methylguanidine                                         
N-methyl-2-bromo-4-chloro-6-                                              
                  1-(2-bromo-4-chloro-6-fluorophenyl)-1-                  
fluoroaniline     methylguanidine                                         
N-methyl-2-chloro-4-iodo-6-                                               
                  1-(2-chloro-4-iodo-6-bromophenyl)-1-                    
bromoaniline      methylguanidine                                         
N-methyl-2,4,6-tribromoaniline                                            
                  1-(2,4,6-tribromophenyl)-1-methylguanidine              
N-methyl-2,4,6-trifluoroaniline                                           
                  1-(2,4,6-trifluorophenyl)-1-methylguanidine             
N-ethyl-2,6-dichloroaniline                                               
                  1-(2,6-dichlorophenyl)-1-ethylguanidine                 
N-ethyl-2,4-dichloroaniline                                               
                  1-(2,4-dichlorophenyl)-1-ethylguanidine                 
N-ethyl-p-fluoroaniline                                                   
                  1-(p-fluorophenyl)-1-ethylguanidine                     
N-propyl-p-fluoroaniline                                                  
                  1-(p-fluorophenyl)-1-propylguanidine                    
N-i-propyl-p-fluoroaniline                                                
                  1-(p-fluorophenyl)-1-i-propylguanidine                  
N-butyl-p-fluoroaniline                                                   
                  1-(p-fluorophenyl)-1-butylguanidine                     
__________________________________________________________________________
 
    
     EXAMPLE 3 
     1-(2,6-dichlorophenyl)-3-methylguanidine 
     To 51 g (0.315 mole) of 2,6-dichloroaniline is added 0.4 moles of ethereal HCl and 200 ml of m-cresol. The mixture is then stirred and heated on a steam bath to drive off the ether and excess hydrogen chloride. To the resultant mixture is then added 17.7 g (0.315 mole) of methyl cyanamide then heated for 2 hours on a steam bath. The reaction mixture is then cooled, added to 150 ml of conc. sodium hydroxide solution, cooled and extracted with 2 liters of ether. The ether layer is washed with 2×1 liter of water, dried over sodium sulfate, charcoaled and evaporated. The residue is triturated with hexane and the precipitate is filtered off and washed with ether and dried to obtain 1-(2,6-dichlorophenyl)-3-methylguanidine hydrochloride. 
     The free base is prepared by dissolving 1-(2,6-dichlorophenyl)-3-methylguanidine hydrochloride to 10% sodium hydroxide solution and extracting with ether. The ether is dried and evaporated to dryness to obtain 1-(2,6-dichlorophenyl)-3-methylguanidine. 
     When the above procedures are followed using the cyanamides of Table I below, then the corresponding products are prepared. 
     TABLE I 
     ethylcyanamide 
     propylcyanamide 
     1-propylcyanamide 
     butylcyanamide 
     pentylcyanamide 
     hexylcyanamide 
     heptylcyanamide 
     octylcyanamide 
     vinylcyanamide 
     propargylcyanamide 
     methallylcyanamide 
     2,4-pentadienylcyanamide 
     2-pentenylcyanide 
     cyclopropylcyanamide 
     cyclobutylcyanamide 
     cyclopentylcyanamide 
     cyclohexylcyanamide 
     phenylcyanamide 
     benzylcyanamide 
     phenethylcyanamide 
     cyclohex-2-enylcyanamide 
     cyclopropylmethylcyanamide 
     cyclobutylmethylcyanamide 
     cyclopropylethylcyanamide 
     When the anilines of Examples 1 and 2 are condensed with the above cyanamides using the above procedures, then the corresponding products are obtained. 
     EXAMPLE 4 
     1-(p-fluorophenyl)-3-methylthiourea 
     To a mixture of 55.5 g (0.5 mole) of p-fluoroaniline and 100 ml of xylene is added 36.5 g (0.5 mole) of methylisothiocyanate and the mixture is refluxed for 2 hours. The reaction product is cooled, titurated with heptane and filtered. Recrystallization from 1:1 iospropanol/water results in 1-(p-fluorophenyl)-3-methylthiourea. 
     When the above procedure is followed using 2,6-dichloroaniline then the product prepared is 1-(2,6-dichlorophenyl)-3-methylthiourea. 
     When the above procedure is followed using the anilines of Examples 1 and 2 then the corresponding product is obtained. 
     When methylisothiocyanate is replaced by the isothiocyanates of Table I below, then the coresponding product is obtained. 
     TABLE I 
     ethylisothiocyanate 
     propylisothiocyanate 
     1-propylisothiocyanate 
     butylisothiocyanate 
     pentylisothiocyanate 
     hexylisothiocyanate 
     heptylisothiocyanate 
     octylisothiocyanate 
     vinylisothiocyanate 
     propargylisothiocyanate 
     methallylisothiocyanate 
     cyclopropylisothiocyanate 
     cyclobutylisothiocyanate 
     cyclopentylisothiocyanate 
     cyclohexylisothiocyanate 
     cyclohex-2-enyliosthiocyanate 
     phenyliosthiocyanate 
     benzylisothiocyanate 
     phenethylisothiocyanate 
     cyclopropylmethylisothiocyanate 
     cyclobutylmethylisothiocyanate 
     cyclopropylethylisothiocyanate 
     EXAMPLE 5 
     1-(2,6-dichlorophenyl)-3-methylguanidine 
     1-(2,6-dichlorophenyl)-3-benzoylthiourea 
     To 51.8 g (0.68 mole) of ammonium thiocyanate in 300 ml acetone is added 86.8 g (0.62 mole) of benzyl chloride. The reaction mixture is refluxed for about 5 min. and then 100 g (0.62 mole) of 2,6-dichloroaniline in 200 ml acetone is added at a rate to maintain reflux. The mixture is refluxed for 11/2 hours, cooled, poured into 11/2 liters of ice and water, filtered to obtain 1-(2,6-dichlorophenyl)-3-benzoylthiourea. 
     2,6-dichlorophenylthiourea 
     182.8 g (0.56 mole) of the latter is heated with 260 ml of 10% sodium hydroxide, filtered, acidified while hot with conc. hydrochloric acid and then made basic with conc. ammonium hydroxide. The mixture is then chilled in an ice bath and the resultant 2,6-dichlorophenylthiourea is filtered off. 
     1-(2,6-dichlorophenyl)-2-methylpseudothiouronium iodide 
     20 g (0.09 mole) of 2,6-dichlorophenylthiourea is combined with 200 ml methanol and 12.9 g (0.09 mole) iodomethane and refluxed for 4 hours. This is then evaporated to dryness and 100 ml hexane is added and the mixture filtered to botain 1-(2,6-dichlorophenyl)-2-methylpseudothiouronium iodide. 
     1-(2,6-dichlorophenyl)-3-methylguanidine hydrochloride 
     32.8 g (0.09 mole) of the latter is added to 300 ml of n-butanol. Methylamine gas is bubbled through this solution while refluxing for 24 hours. The reaction mixture is evaporated to dryness and extracted with 10% sodium hydroxide solution and ether. The ether is washed with 10% sodium hydroxide and then with water, dried and filtered. To this is added ethereal HCl and the precipitate is collected to obtain 1-(2,6-dichlorophenyl)-3-methylguanidine hydrochloride. 
     The free base is prepared by dissolving 1-(2,6-dichlorophenyl)-3-methylguanidine hydrochloride in 10% sodium hydroxide solution and extracting with ether. The ether is dried and evaporated to dryness to obtain 1-(2,6-dichlorophenyl)-3-methylguanidine. 
     When the above procedures are followed using the anilines of Examples 1 and 2, then the corresponding product is obtained. 
     When the above procedures are followed and methylamine is replaced with the amines of Table I below, then the corresponding product is obtained. 
     TABLE I 
     ethylamine 
     propylamine 
     1-propylamine 
     butylamine 
     pentylamine 
     hexylamine 
     heptylamine 
     octylamine 
     propargylamine 
     methallylamine 
     2,4-pentadienylamine 
     cyclopropylamine 
     cyclobutylamine 
     cyclopentylamine 
     cyclohexylamine 
     propionamide 
     aniline 
     benzylamine 
     phenethylamine 
     cyclohex-2-enylamine 
     cyclopropylmethylamine 
     cyclobutylmethylamine 
     cyclopropylethylamine 
     N-benzylaniline 
     azetidine 
     piperidine 
     homopiperidine 
     morpholine 
     pyrollidine 
     piperazine 
     2-methyl-1-azacyclooctane 
     When the above procedures are followed using the anilines of Examples 1 and 2 and the amines of Table I above the corresponding products are obtained. 
     When the thiourea compounds prepared of Example 4 are substituted in the above procedure, then the corresponding products are obtained. 
     EXAMPLE 6 
     1-(2,6-dichlorophenylamidino)-3-(t-butyl)urea 
     To a mixture of 10 g (0.05 mole) of 2,6-dichlorophenylguanidine and 10 ml xylene is added 5 g of t-butylisocyanate (0.05 mole) and the mixture is refluxed for 2 hours. The reaction product is cooled, triturated with heptane and filtered. Recrystallization from 1:1 isopropanol/water results in 1-(2,6-dichlorophenylamidino)-3-(t-butyl)urea. 
     When the above procedure is followed using the guanidines of Example 1, then the corresponding products of Table I below are prepared. 
     TABLE I 
     1-(o-chlorophenylamidino)-3-(t-butyl)urea 
     1-(m-chlorophenylamidino)-3-(t-butyl)urea 
     1-(p-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2,3-dichlorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dichlorophenylamidino)-3-(t-butyl)urea 
     1-(2,5-dichlorophenylamidine)-3-(t-butyl)urea 
     1-(3,4-dichlorophenylamidino)-3-(t-butyl)urea 
     1-(3,5-dichlorophenylamidino)-3-(t-butyl)urea 
     1-(2,3,4-trichlorophenylamidino)-3-(t-butyl)urea 
     1-(2,3,5-trichlorophenylamidino)-3-(t-butyl)urea 
     1-(2,3,6-trichlorophenylamidino)-3-(t-butyl)urea 
     1-(2,4,5-trichlorophenylamidino)-3-(t-butyl)urea 
     1-(2,4,6-trichlorophenylamidino)-3-(t-butyl)urea 
     1-(3,4,5-trichlorophenylamidino)-3-(t-butyl)urea 
     1-(o-bromophenylamidino)-3-(t-butyl)urea 
     1-(m-bromophenylamidino)-3-(t-butyl)urea 
     1-(p-bromophenylamidino)-3-(t-butyl)urea 
     1-(2,3-dibromophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dibromophenylamidino)-3-(t-butyl)urea 
     1-(2,5-dibromophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dibromophenylamidino)-3-(t-butyl)urea 
     1-(3,4-dibromophenylamidino)-3-(t-butyl)urea 
     1-(3,5-dibromophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-3-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-5-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-6-bromophenylamidino)-3-(t-butyl)urea 
     1-(3-chloro-2-bromophenylamidino)-3-(t-butyl)urea 
     1-(3-chloro-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(3-chloro-5-bromophenylamidino)-3-(t-butyl)urea 
     1-(3-chloro-6-bromophenylamidino)-3-(t-butyl)urea 
     1-(4-chloro-2-bromophenylamidino)-3-(t-butyl)urea 
     1-(4-chloro-3-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-fluoro-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-fluoro-6-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-fluoro-6-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-bromo-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-iodo-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-iodo-6-chlorophenylamidino)-3(t-butyl)urea 
     1-(2-chloro-4-iodophenylamidino)-3-(t-butyl)urea 
     1-(2-iodo-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(o-fluorophenylamidino)-3-(t-butyl)urea 
     1-(m-fluorophenyamidino)-3-(t-butyl)urea 
     1-(p-fluorophenylamidino)-3-(t-butyl)urea 
     1-(p-iodophenylamidino)-3-(t-butyl)urea 
     1-(2,4-difluorophenylamidino)-3-(t-butyl)urea 
     1-(2,5-difluorophenylamidino)-3-(t-butyl)urea 
     1-(2,6-difluorophenylamidino)-3-(t-butyl)urea 
     1-(2,6-difluorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-diiodophenylamidino)-3-(t-butyl)urea 
     1-(2-iodo-6-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-bromo-4-iodophenylamidino)-3-(t-butyl)urea 
     1-(2-fluoro-4-iodophenylamidino)-3-(t-butyl)urea 
     1-(2-iodo-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(o-trifluoromethylphenylamidino)-3-(t-butyl)urea 
     1-(m-trifluoromethylphenylamidino)-3-(t-butyl)urea 
     1-(p-trifluoromethylphenylamidino)-3-(t-butyl)urea 
     1-(p-trifluoromethoxyphenylamidino)-3-(t-butyl)urea 
     1-(p-methylsulfonylphenylamidino)-3-(t-butyl)urea 
     1-(1-nitrophenylamidino)-3-(t-butyl)urea 
     1-(m-nitrophenylamidino)-3-(t-butyl)urea 
     1-(p-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-bromo-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-iodo-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-fluoro-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-nitro-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-nitro-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-nitro-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-nitro-4-trifluoromethylphenylamidino)-3-(t-butyl)urea 
     1-(2-nitro-4-methoxyphenylamidino)-3-(t-butyl)urea 
     1-(2-cyano-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-chlroo-4-cyanophenylamidino)-3-(t-butyl)urea 
     1-(2-methyl-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-methyl-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-trifluoromethyl-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-trifluoromethyl-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-trifluoromethyl-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(4-trifluoromethyl-2-chlorophenylamidino)-3-(t-butyl)urea 
     1-(4-trifluoromethyl-2-bromophenylamidino)-3-(t-butyl)urea 
     1-(4-trifluoromethyl-2-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dichloro-6-methylphenylamidino)-3-(t-butyl)urea 
     1-(2,6-dichloro-4-methylphenylamidino)-3-(t-butyl)urea 
     1-(3,5-ditrifluoromethylphenylamidino)-3-(t-butyl)urea 
     1-(2-methoxy-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-trifluoromethyl-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dichloro-6-methoxyphenylamidino)-3-(t-butyl)urea 
     1-(2,6-dimethyl-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dimethyl-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dimethyl-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dimethyl-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dimethyl-4-trifluoromethylphenylamidino)-3-(t-butyl)urea 
     1-(2-ethyl-4-nitrophenylamidino)-3-(t-butyl)urea 
     1-(2-ethyl-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-ethyl-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(2-ethyl-4-fluorophenylamidino-3-(t-butyl)urea 
     1-(2-ethyl-4-trifluoromethylphenylamidino)-3-(t-butyl)urea 
     1-(2-ethyl-4-cyanophenylamidino)-3-(t-butyl)urea 
     1-(2-ethyl-4-methylsulfonylphenylamidino)-3-(t-butyl)urea 
     1-(2,4-dichloro-6-bromophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dichloro-4-bromophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dibromo-6-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dibromo-4-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dichloro-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-methyl-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dimethyl-6-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dimethyl-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-fluoro-6-methylphenylamidino)-3-(t-butyl)urea 
     1-(2,6-dichloro-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,5-dichloro-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dichloro-6-iodophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dichloro-4-iodophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dibromo-6-iodophenylamidino)-3-(t-butyl)urea 
     1-(2,4-dibromo-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2,6-dibromo-4-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-bromo-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-bromo-4-fluoro-6-chlorophenylamidino)-3-(t-butyl)urea 
     1-(2-bromo-4-chloro-6-fluorophenylamidino)-3-(t-butyl)urea 
     1-(2-chloro-4-iodo-6-bromophenylamidino)-3-(t-butyl)urea 
     1-(2,4,6-tribromophenylamidino)-3-(t-butyl)urea 
     1-(2,4,6-trifluorophenylamidino)-3-(t-butyl)urea 
     When t-butylisocyanate in the above procedure is replaced by the isocyanates of Table II below, then the corresponding product is prepared. 
     TABLE II 
     methylisocyanate 
     ethylisocyanate 
     propylisocyanate 
     1-propylisocyanate 
     butylisocyanate 
     pentylisocyanate 
     hexylisocyanate 
     heptylisocyanate 
     octylisocyanate 
     propargylisocyanate 
     methallylisocyanate 
     cyclopropylisocyanate 
     cyclobutylisocyanate 
     cyclopentylisocyanate 
     cyclohexylisocyanate 
     cyclohex-2-enylisocyanate 
     phenylisocyanate 
     benzylisocyanate 
     phenethylisocyanate 
     cyclopropylmethylisocyanate 
     cyclobutylmethylisocyanate 
     cyclopropylethylisocyanate 
     When the above procedure is followed using the guanidines of Example 1 and 3 and the isocyanates of Table II above, then the corresponding product is prepared. 
     EXAMPLE 7 
     1-(2,6-dichlorophenyl-N-methylamidino)urea 
     1-(2,6-dichlorophenyl-N-methylamidino)-3-(t-butyl)urea 
     To a mixture of 10.9 g (0.05 mole) of 1-(2,6-dichlorophenyl)-1-methylguanidine and 10 ml xylene is added 5 g of t-butylisocyanate (0.05 mole) and the mixture is refluxed for 2 hours. The reaction product is cooled, triturated with heptane and filtered. Recrystallization from 1:1 isopropanol/water results in 1-(2,6-dichlorophenyl-N-methylamidino)-3-(t-butyl)urea. 
     1-(2,6-dichlorophenyl-N-methylamidino)urea 
     A mixture as 33.7 g (0.106 mole) of 1-(2,6-dichlorophenyl-N-methylamidino)-3-(t-butyl)urea and 200 ml of conc. hydrochloric acid is refluxed for 1/2 hour. The reaction mixture is cooled, filtered and washed with 10 ml of 1:1 HCl/H 2  O and dried. The product is then recrystallized from ethanol-ether to obtain 1-(2,6-dichlorophenyl-N-methylamidino)urea. 
     When the above procedure is followed using 1-(2,6-dichlorophenyl)-3-methylguanidine and 1-(2,6-dichlorophenyl)-1,3-dimethylguanidine then the products prepared are 1-(2,6-dichlorophenylamidino)-1-methylurea and 1-(2,6-dichlorophenyl-N-methylamidino)-1-methylurea. 
     When the above procedure is followed using the guanidines of Examples 2, 3 and 5, then the corresponding products are prepared. 
     EXAMPLE 8 
     1-(2,6-dichlorophenyl)-3-carbamylthiourea 
     1-(2,6-dichlorophenyl)-3-(t-butylcarbamyl)thiourea 
     To a mixture of 11 g (0.05 mole) of 1-(2,6-dichlorophenyl)thiourea and 10 ml of xylene is added 5 g of t-butylisocyanate (0.05 mole) and the mixture is refluxed for 2 hours. The reaction product is cooled, triturated with heptane and filtered. Recrystallization from 1:1 isopropanol/water results in 1-(2,6-dichlorophenyl)-3-(t-butylcarbamyl)thiourea. 
     1-(2,6-dichlorophenyl)-3-carbamylthiourea 
     A mixture of 32 g (0.1 mole) of 1-(2,6-dichlorophenyl)3-(t-butylcarbamyl)thiourea and 200 ml of conc. hydrochloric acid is refluxed for 1/2 hour. The reaction mixture is cooled, filtered and washed with 10 ml of 1:1 HCl/H 2  O and dried. The product is then recrystallized from ethanolether to obtain 1-(2,6-dichlorophenyl)-3-carbamylthiourea. 
     When the above procedure is followed using 1-(2,6-dichlorophenyl)-1-methylthiourea; 1-(2,6-dichlorophenyl)-3-methylthiourea; 1-(2,6-dichlorophenyl)-1,3-dimethylthiourea; 1-(p-fluorophenyl)-3-methylthiourea then the products obtained are 1-(2,6-dichlorophenyl)-1-methyl-3-carbamylthiourea; 1-(2,6-dichlorophenyl)-3-methyl-3-carbamylthiourea; 1-(2,6-dichlorophenyl)-1,3-dimethyl-3-cabamylthiourea; and 1-(p-fluorophenyl)-3-methyl-3-carbamylthiourea. 
     When the above procedure is followed using the thiourea compounds of Examples 4 and 5 then the corresponding product is obtained. 
     When the above procedure is followed using the substituted isocyanate compounds of Table II, Example 6, then the corresponding product is obtained. 
     When the above procedure is followed using the thiourea compounds of Examples 4 and 5 and the substituted isocyanate compounds of Table II, Example 6, then the corresponding product is obtained. 
     EXAMPLE 9 
     1-(2,6-dichlorophenyl-N&#39;-methylamidino)urea 
     1-(2,6-dichlorophenyl)-3-carbamyl-2-methylthiouronium iodide 
     26.4 g (0.1 mole) of 1-(2,6-dichlorophenyl)-3-carbamylthiourea is combined with 200 ml of methanol and 14.1 g (0.1 mole) of iodomethane and refluxed for 4 hours. This is then evaporated to dryness and 100 ml of hexane is added. The mixture is filtered to obtain 1-(2,6-dichlorophenyl)-3-carbamyl-3-methylthiouronium iodide. 
     1-(2,6-dichlorophenyl-N&#39;-methylamidino)urea 
     40.5 g of 1-(2,6-dichlorophenyl)-3-carbamyl-2-methylthiouronium iodide (0.1 mole) is added to 300 ml of n-butanol. Methylamine gas is bubbled through this solution while refluxing for 24 hours. The reaction mixture is evaporated to dryness and extracted with 10% sodium hydroxide solution and ether. The ether is washed with 10% sodium hydroxide and then with water; dried and filtered. To this is added ethereal HCl and the precipitate is collected to obtain 1-(2,6-dichlorophenyl-N&#39;-methylamidino)urea hydrochloride. 
     The free base is prepared by dissolving the above hydrochloride in 10% sodium hydroxide solution and extracting with ether. The ether is dried and evaporated to dryness to obtain 1-(2,6-dichlorophenyl-N&#39;-methylamidino)urea. 
     When the above procedure is followed using the thiourea compounds prepared by Example 8, then the corresponding amidinourea is prepared. 
     When the above procedure is followed and methylamine is replaced with the amines of Table I, Example 5, then the corresponding product is obtained. 
     When the above procedure is followed using the thiourea compounds prepared by Example 8 and the amines of Table I, Example 5, then the corresponding product is prepared. 
     EXAMPLE 10 
     1-(2,6-dichlorophenylamidino)-3,3-(α,α&#39;-dimethylpentamethylene)urea 
     A. 2,6-dimethylpiperidinoyl chloride 
     To a solution of 50 g of 2,6-dimethylpiperidine in 300 ml of benzene is added 60 g of phosgene and the mixture is refluxed for 3 hours. The solid which had separated was filtered and the filtrate was concentrated and distilled under vacuum to obtain 2,6-dimethylpiperidinoyl chloride. 
     B. 1-(2,6-dichlorophenylamidino)-3,3-(α,α&#39;-dimethylpentamethylene)urea 
     To a mixture of 20.4 g (0.1 mole) of 2,6-dichlorophenylguanidine in 250 ml of dimethylformamide is added dropwise with stirring a solution of 17.5 g (0.1 mole) of w,6-dimethylpiperidinoyl chloride in 150 ml of tetrahydrofuran. The mixture is stirred for 6 hours, poured onto ice, acidified with conc. HCl basified with sodium hydroxide and extracted with ether. The ether is washed with water and saturated sodium chloride sodium and dried over magnesium sulfate. The filtered solution is evaporated to dryness to obtain 1-(2,6-dichlorophenyl)-3,3-(α,α&#39;-dimethylpontamethylene)urea. 
     The hydrochloride salt is prepared by dissolving the above free base in ether and adding ethereal hydrochloric acid. The formed hydrochloride is separated and recrystallized from acetonitrile/water/conc. HCl. 
     When 2,6-dimethylpiperidine is replaced in the above example by the amines of Table I below, then the corresponding product is prepared. 
     TABLE I 
     piperidine 
     4-methylpiperidine 
     N-methylpiperazine 
     N-methylhomopiperazine 
     morpholine 
     thiazolidine 
     octamethyleneamine 
     2-methylazacyclooctane 
     pyrrolidine 
     dimethylamine 
     diethylamine 
     methylethylamine 
     ethylpropylamine 
     ethylcyclopropylamine 
     ethylbenzylamine 
     dibenzylamine 
     dicyclopropylamine 
     methylcyclobutylamine 
     methyl-t-butylamine 
     ethyl-t-butylamine 
     cyclopropyl-t-butylamine 
     methyl(cyclopropylmethyl)amine 
     When 2,6-dichlorophenylguanidine in the above Example is replaced by the guanidines prepared in Examples 1, 2, 3 and 5, then the corresponding product is obtained. 
     When the above procedure is followed, and 2,6-dichlorophenylguanidine is replaced by the guanidines of Examples 1, 2, 3 and 5 and 2,6-dimethylpiperidine is replaced by the amines of Table I above, then the corresponding product is prepared. 
     EXAMPLE 11 
     1-(2,6-dichlorophenyl-N&#39;-methylamidino)-3,3-diethylurea 
     A. 1-(2,6-dichlorophenyl)-3,3-diethylcarbamylthiourea 
     To a mixture of 11 g (0.05 mole) of 1-(2,6-dichlorophenyl)thiourea in 150 ml of dimethylformamide is added dropwise with stirring a solution of 6.75 g (0.01 mole) of diethylcarbamyl chloride in 100 ml of tetrahydrofuran (prepared from diethylamine and phosgene according to Example 10). The mixture is stirred for 10 hours, poured onto ice, acidified with conc. HCl while keeping the mixture at ice temperature and basified with sodium hydroxide and extracted with ether. The ether is washed, dried and evaporated to obtain 1-(2,6-dichlorophenyl)-3,3-diethylcabamylthiourea. 
     B. 1-(2,6-dichlorophenyl)-3-(N,N-diethylcarbamyl)-2-methylthiouronium iodide 
     (0.1 mole) of 1-(2,6-dichlorophenyl)-3-(N,N-diethylcarbamyl) thiourea is combined with 200 ml of methanol and 14.1 g (0.1 mole) of iodomethane and refluxed for 4 hours. This is then evaporated to dryness and 100 ml of hexane is added. The mixture is filtered to obtain 1-(2,6-dichlorophenyl)-3-(N,N-diethylcarbamyl)-2-methylthiouronium iodide. 
     C. 1-(2,6-dichlorophenyl-N&#39;-methylamidino)-3,3-diethylurea 
     46.2 g of 1-(2,6-dichlorophenyl)-3-(N,N-diethylcarbamyl)-2-methylthiouronium iodide (0.1 mole) is added to 300 ml of n-butanol. Methylamine gas is bubbled through this solution while refluxing for 24 hours. The reaction mixture is evaporated to dryness and extracted with 10% sodium hydroxide solution and ether. The ether is washed with 10% sodium hydroxide and then with water; dried filtered and evaporated to dryness to obtain 1-(2,6-dichlorophenyl-N&#39;-methylamidino)-3,3-diethylurea. 
     The hydrochloride salt is prepared by dissolving the above free base in ether and adding ethereal hydrochloric acid. The formed hydrochloride is separated and recrystallized from acetonitrile/water conc. HCl. 
     When diethylamine is replaced in the above example by the amines of Table I, Example 10, then the corresponding product is obtained. 
     When 1-(2,6-dichlorophenyl)thiourea is replaced with the thioureas prepared in Examples 4 and 5 then the corresponding product is obtained. 
     When 1-(2,6-dichlorophenyl)thiourea is replaced with the thioureas of Examples 4 and 5 and diethylamine is replaced by the amines of Table I, Example 10, then the corresponding product is obtained. 
     
         __________________________________________________________________________
Starting Materials               Products                 Example         
__________________________________________________________________________
2,6-dichlorophenylguanidine + methylisocyanate                            
                                 1-(2,6-dichlorophenylamidino)-3-methylure
                                 a                        6               
2,6-dichlorophenylguanidine + ethylisocyanate                             
                                 1-(2,6-dichlorophenylamidino)-3-ethylurea
                                 2                        6               
2,6-dichlorophenylguanidine + propylisocyanate                            
                                 1-(2,6-dichlorophenylamidino)-3-propylure
                                 a                        6               
2,6-dichlorophenylguanidine + i-propylisocyanate                          
                                 1-(2,6-dichlorophenylamidino)-3-i-propylu
                                 rea                      6               
2,6-dichlorophenylguanidine + butylisocyanate                             
                                 1-(2,6-dichlorophenylamidino)-3-butylurea
                                                          6               
2,6-dichlorophenylguanidine + pentylisocyanate                            
                                 1-(2,6-dichlorophenylamidino)-3-pentylure
                                 a                        6               
2,6-dichlorophenylguanidine + hexylisocyanate                             
                                 1-(2,6-dichlorophenylamidino)-3-hexylurea
                                                          6               
2,6-dichlorophenylguanidine + heptylisocyanate                            
                                 1-(2,6-dichlorophenylamidino)-3-heptylure
                                 a                        6               
2,6-dichlorophenylguanidine + octylisocyanate                             
                                 1-(2,6-dichlorophenylamidino)-3-octylurea
                                                          6               
2,6-dichlorophenylguanidine + allyl isocyanate                            
                                 1-(2,6-dichlorophenylamidino)-3-allyl    
                                 urea                     6               
2,6-dichlorophenylguanidine + propargylisocyanate                         
                                 1-(2,6-dichlorophenylamidino)-3-propargyl
                                 urea                     6               
2,6-dichlorophenylguanidine + methallylisocyanate                         
                                 1-(2,6-dichlorophenylamidino)-3-methallyl
                                 urea                     6               
2,6-dichlorophenylguanidine + cyclopropylisocyanate                       
                                 1-(2,6-dichlorophenylamidino)-3-cycloprop
                                 ylurea                   6               
2,6-dichlorophenylguanidine + cyclobutylisocyanate                        
                                 1-(2,6-dichlorophenylamidino)-3-cyclobuty
                                 lurea                    6               
2,6-dichlorophenylguanidine + cyclopentylisocyanate                       
                                 1-(2,6-dichlorophenylamidino)-3-cyclopent
                                 ylurea                   6               
2,6-dichlorophenylguanidine - cyclohexylisocyanate                        
                                 1-(2,6-dichlorophenylamidino)-3-cyclohexy
                                 lurea                    6               
2,6-dichlorophenylguanidine + (cyclohex-2-enyl)isocyanate                 
                                 1-(2,6-dichlorophenylamidino)-3-(cyclohex
                                 -2-enyl)-                6               
                                 urea                                     
2,6-dichlorophenylguanidine + phenylisocyanate                            
                                 1-(2,6-dichlorophenylamidino)-3-phenylure
                                 a                        6               
2,6-dichlorophenylguanidine + benzylisocyanate                            
                                 1-(2,6-dichlorophenylamidino)-3-benzylure
                                 a                        6               
2,6-dichlorophenylguanidine + phenethylisocyanate                         
                                 1-(2,6-dichlorophenylamidino)-3-phenethyl
                                 urea                     6               
2,6-dichlorophenylguanidine + cyclopropylmethylisocyanate                 
                                 1-(2,6-dichlorophenylamidino)-3-cycloprop
                                 ylmethyl-                6               
                                 urea                                     
2,6-dichlorophenylguanidine + cyclobutylmethylisocyanate                  
                                 1-(2,6-dichlorophenylamidino)-3-cyclobuty
                                 lmethyl-                 6               
                                 urea                                     
2,6-dichlorophenylguanidine + cyclopropylethylisocyanate                  
                                 1-(2,6-dichlorophenylamidino)-3-cycloprop
                                 ylethyl-                 6               
                                 urea                                     
2,6-dichlorophenylguanidine + piperidinoyl chloride                       
                                 1-(2,6-dichlorophenylamidino)-3,3-pentame
                                 thylene-                 10              
                                 urea                                     
2,6-dichlorophenylguanidine + 4-methylpiperidinoyl chloride               
                                 1-(2,6-dichlorophenylamidino)-3,3-γ
                                 -methylpenta-            10              
                                 methyleneurea                            
2,6-dichlorophenylguanidine + N-methylpiperazinoyl chloride               
                                 1-(2,6-dichlorophenylamidino)-3,3-(N-meth
                                 yl-3&#39;-                   10              
                                 azapentamethylene)urea                   
2,6-dichlorophenylquanidine + N-methylhomopiperazinoyl chloride           
                                 1-(2,6-dichlorophenylamidino)-3,3-(N-meth
                                 yl-3&#39;-                   10              
                                 azapentamethylene)urea                   
2,6-dichlorophenylguanidine + morpholinoyl chloride                       
                                 1-(2,6-dichlorophenylamidino)-3,3-(3&#39;-osc
                                 apenta-                  10              
                                 methylene)urea                           
2,6-dichlorophenylguanidine + thiazolidinoyl chloride                     
                                 1-(2,6-dichlorophenylamidino)-3,3-(2&#39;-thi
                                 atetra-                  10              
                                 methylene)urea                           
2,6-dichlorophenylguanidine + N,N-octamethylenecarbamyl                   
                                 1-(2,6-dichlorophenylamidino)-3,3-octamet
                                 hylene-                  10              
chloride                         urea                                     
2,6-dichlorophenylguanidine + 2-methyl-N,N-octametylene-                  
                                 1-(2,6-dichlorophenylamidino)-3,3-α
                                 -methylocta-             10              
carbamyl chloride                methyleneurea                            
2,6-dichlorophenylguanidine + pyrrolidinoyl chloride                      
                                 1-(2,6-dichlorophenylamidino)-3,3-tetrame
                                 thyleneurea              10              
2,6-dichlorophenylguanidine + N,N-dimethylcarbamyl chloride               
                                 1-(2,6-dichlorophenylamidino)-3,3-dimethy
                                 lurea                    10              
2,6-dichlorophenylguanidine + N,N-diethylcarbamyl chloride                
                                 1-(2,6-dichlorophenylamidino)-3,3-diethyl
                                 urea                     10              
2,6-dichlorophenylguanidine + N-ethyl-N-methylcarbamyl chloride           
                                 1-(2,6-dichlorophenylamidino)-3-ethyl-3-m
                                 ethylurea                10              
2,6-dichlorophenylguanidine + N-ethyl-N-propylcarbamyl chloride           
                                 1-(2,6-dichlorophenylamidino)-3-ethyl-3-p
                                 ropylurea                10              
2,6-dichlorophenylguanidine + N-cyclopropyl-N-ethylcarbamyl               
                                 1-(2,6-dichlorophenylamidino)-3-cycloprop
                                 yl-3-ethyl-              10              
chloride                         urea                                     
2,6-dichlorophenylguanidine + N-benzyl-N-ethylcarbamyl chloride           
                                 1-(2,6-dichlorophenylamidino)-3-benzyl-3-
                                 ethylurea                10              
2,6-dichlorophenylguanidine + N,N-dibenzylcarbamyl chloride               
                                 1-(2,6-dichlorophenylamidino)-3,3-dibenzy
                                 lurea                    10              
2,6-dichlorophenylguanidine + N,N-dicyclopropylcarbamyl                   
                                 1-(2,6-dichlorophenylamidino)-3,3-dicyclo
                                 propylurea               10              
chloride                                                                  
2,6-dichlorophenylguanidine + N-cyclobutyl-N-methylcarbamyl               
                                 1-(2,6-dichlorophenylamidino)-3-cyclobuty
                                 l-3-methyl               10              
chloride                                                                  
1-(2,6-dichlorophenyl)-1-methylguanidine + methylisocyanate               
                                 1-(2,6-dichlorophenyl-N-methylamidino)-3-
                                 methylurea               7               
1-(2,6-dichlorophenyl)-3-(N-methylcarbamyl)-2-methylthio-                 
                                 1-(2,6-dichlorophenyl-N&#39;-methylamidino)-3
                                 -methyl-                 9               
uronium iodide + methylamine     urea                                     
1-(2,6-dichlorophenyl)-3-(N-t-butylcarbamyl)-2-methylthio-                
                                 1-(2,6-dichlorophenyl-N&#39;-methylamidino)-3
                                 -t-butyl-                9               
uronium iodide + methylamine     urea                                     
1-(2,6-dichlorophenyl)-3-methylguanidine + methylisocyanate               
                                 1-(2,6-dichlorophenylamidino)-1,3-dimethy
                                 lurea                    6               
1-(2,6-dichlorophenyl)-3-methylguanidine + t-butylisocyanate              
                                 1-(2,6-dichlorophenylamidino)-1-methyl-3-
                                 t-butylurea              6               
1-(2,6-dichlorophenyl)-1,3-dimethylguanidine + t-butyl-                   
                                 1-(2,6-dichlorophenyl-N-methylamidino)-1-
                                 methyl-3-t-              6               
isocyanate                       butylurea                                
1-(2,6-dichlorophenyl)-3-methyl-3-(N-t-butylcarbamyl)-2-methyl-           
                                 1-(2,6-dichlorophenyl-N&#39;-methylamidino)-1
                                 -methyl-3-t-             9               
thiouronium iodide) + methylamine                                         
                                 butylurea                                
1-(2,6-dichlorophenyl)-1,3-dimethyl-3-(N-t-butylcarbamyl)-2-              
                                 1-(2,6-dichlorophenyl-N,N&#39;-dimethylamidin
                                 o)-1-methyl-             9               
methylthiouronium iodide) + methylamine                                   
                                 3-t-butylurea                            
1-(2,6-dichlorophenyl)-1,3-dimethyl-3-(N-methylcarbamyl)-2-               
                                 1-(2,6-dichlorophenyl-N,N&#39;-dimethylamidin
                                 o)-1,3-                  9               
methylthiouronium iodide) + methylamine                                   
                                 dimethylurea                             
p-fluorophenylguanidine + methylisocyanate                                
                                 1-(p-fluorophenylamidino)-3-methylurea   
                                                          6               
1-(p-fluorophenyl)-1-methylguanidine + t-butylisocyanate                  
                                 1-(p-fluorophenyl-N-methylamidino)-3-(t-b
                                 utyl)urea                7               
1-(p-fluorophenyl-N-methylamidino)-3-(t-butyl)urea + conc.                
                                 1-(p-fluorophenyl-N-methylamidino)urea   
                                                          7               
1-(p-fluorophenyl)-3-methylguanidine + t-butylisocyanate                  
                                 1-(p-fluorophenylamidino)-1-methyl-3-(t-b
                                 utyl)urea                7               
1-(p-fluorophenyl)-1,3-dimethylguanidine + t-butylisocyanate              
                                 1-(p-fluorophenyl-N-methylamidino)-1-meth
                                 yl-3-(t-                 7               
                                 butyl)urea                               
1-(p-fluorophenylamidino)-1-methyl-3-(t-butyl)urea                        
                                 1-(p-fluorophenylamidino)-1-methylurea   
                                                          7               
1-(p-fluorophenyl-N-methylamidino)-1-methyl-3-(t-butyl)urea               
                                 1-(p-fluorophenyl-N-methylamidino)-1-meth
                                 ylurea                   7               
1-(p-fluorophenyl)-3-carbamyl-2-methylthiouronium iodide                  
                                 1-(p-fluorophenyl-N&#39;-methylamidino)urea  
                                                          9               
methylamine                                                               
p-fluorophenylguanidine + 2,6-dimethylpiperidinoyl chloride               
                                 1-(p-fluorophenylamidino)-3,3-(α,.a
                                 lpha.&#39;-dimethyl-         10              
                                 pentamethylene)urea                      
1-(p-fluorophenyl)-3-(N,N-diethylcarbamyl)-2-methylthiouronium            
                                 1-(p-fluorophenyl-N&#39;-methylamidino)-3,3-d
                                 iethyl-                  11              
iodide + methylamine             urea                                     
1-(p-fluorophenyl)-1-methylguanidine + methylisocyanate                   
                                 1-(p-fluorophenyl-N-methylamidino)-3-meth
                                 ylurea                   7               
1-(p-fluorophenyl)-3-(N-methylcarbamyl)-2-methylthiouronium               
                                 1-(p-fluorophenyl-N&#39;-methylamidino)-3-met
                                 hylurea                  9               
iodide + methylamine                                                      
1-(p-fluorophenyl)-3-methylguanidine + methylisocyanate                   
                                 1-(p-fluorophenylamidino)-1,3-dimethylure
                                 a                        6               
1-(p-fluorophenyl)-3-methyl-3-(N-methylcarbamyl)-2-methyl-                
                                 1-(p-fluorophenyl-N&#39;-methylamidino)-1,3-d
                                 imethyl-                 9               
thiouronium iodide + methylamine urea                                     
1-(p-fluorophenyl)-1,3-dimethylguanidine + methylisocyanate               
                                 1-(p-fluorophenyl-N-methylamidino)-1,3-di
                                 methyl-                  6               
                                 urea                                     
1-(p-fluorophenyl)-1,3-dimethyl-3-(N-methylcarbamyl)-2-                   
                                 1-(p-fluorophenyl-N,N&#39;-dimethylamidino)-1
                                 ,3-                      9               
methylthiouronium iodide + methylamine                                    
                                 dimethylurea                             
p-(chlorophenylguanidine + piperidinoyl chloride                          
                                 1-(p-chlorophenylamidino)-3,3-(pentamethy
                                 lene)urea                10              
1-(2,4-dichlorophenyl-N-methylamidino-3-t-butyl)urea + conc.              
                                 1-(2,4-dichlorophenyl-N-methylamidino)-ur
                                 ea                       7               
HCl                                                                       
1-(p-bromophenyl)-3-methyl-3-carbamyl-2-methylthiouronium                 
                                 1-(p-bromophenyl-N&#39;-methylamidino)-1-meth
                                 ylurea                   9               
iodide + methylamine                                                      
1-(2-chloro-6-fluorophenyl)guanidine + methylisocyanate                   
                                 1-(2,chloro-6-fluorophenylamidino)-3-ethy
                                 lurea                    7               
1-(p-trifluoromethylphenylamidino)-1-methyl-3-(t-butyl)urea               
                                 1-(p-trifluoromethylphenylamidino)-1-meth
                                 ylurea                   7               
+ conc. HCl                                                               
p-trifluoromethylphenylguanidine + methylisocyanate                       
                                 1-(p-trifluoromethylphenylamidino)-3-meth
                                 ylurea                   6               
p-trifluoromethylphenylguanidine + morpholinoyl chloride                  
                                 1-(p-trifluoromethylphenylamidino)-3,3-(3
                                 &#39;-oxapenta-              10              
                                 methylene)urea                           
1-(p-trifluoromethoxyphenyl-N-ethylamidino)-3-(t-butyl)urea               
                                 1-(p-trifluoromethoxyphenyl-N-ethylamidin
                                 o)urea                   7               
+ conc. HCl                                                               
p-methylsulfonylphenylguanidine + N,N-diethylcarbamyl chloride            
                                 1-(p-methylsulfonylphenylamidino)-3,3-die
                                 thylurea                 10              
p-nitrophenylguanidine + ethylisocyanate                                  
                                 1-(p-nitrophenyl)-3-ethylurea            
                                                          6               
1-(2-chloro-4-cyanophenylamidino)-1-ethyl-3-t-butylurea                   
                                 1-(2-chloro-4-cyanophenylamidino)-1-ethyl
                                 urea                     7               
conc. HCl                                                                 
1-(2-nitro-4-methoxyamidino)-1-ethyl-3-t-butylurea + conc.                
                                 1-(2-nitro-4-methoxyphenylamidino)-1-ethy
                                 lurea                    7               
1-(2-methyl-4-chlorophenyl-N-methylamidino)-3-t-butylurea                 
                                 1-(2-methyl-4-chlorophenyl-N-methylamidin
                                 o)urea                   7               
+ conc. HCl                                                               
1-(2-methyl-4-bromophenyl-N-methylamidino)-3-t-butylurea                  
                                 1-(2-methyl-4-bromophenyl-N-methylamidino
                                 )urea                    7               
+ conc. HCl                                                               
1-(2-methyl-4-fluorophenyl-N-methylamidino)-3-t-butylurea                 
                                 1-(2-methyl-4-fluorophenyl-N-methylamidin
                                 o)urea                   7               
+ conc. HCl                                                               
1-(2-chloro-4-methylphenyl-N-methylamidino)-3-t-butylurea                 
                                 1-(2-chloro-4-methylphenyl-N-methylamidin
                                 o)urea                   7               
+ conc. HCl                                                               
1-(2-fluoro-4-methylphenyl-N-methylamidino)-3-t-butylurea                 
                                 1-(2-fluoro-4-methylphenyl-N-methylamidin
                                 o)urea                   7               
+ conc. HCl                                                               
1-(2-methyl-4-nitrophenyl-N-methylamidino)-3-t-butylurea                  
                                 1-(2-methyl-4-nitrophenyl-N-methylamidino
                                 )urea                    7               
+ conc. HCl                                                               
1-(2-methyl-6-chlorophenyl-N-methylamidino)-3-t-butylurea                 
                                 1-(2-methyl-6-chlorophenyl-N-methylamidin
                                 o)urea                   7               
+ conc. HCl                                                               
1-(2-methyl-6-fluorophenyl-N-methylamidino)-3-t-butylurea                 
                                 1-(2-methyl-6-fluorophenyl-N-methylamidin
                                 o)urea                   7               
+ conc. HCl                                                               
1-(2,4-dimethylphenyl-N-methylamidino)-3-t-butylurea                      
                                 1-(2,4-dimethylphenyl-N-methylamidino)ure
                                 a                        7               
+ conc. HCl                                                               
1-(2,6-dimethylphenyl-N-methylamidino)-3-t-butylurea                      
                                 1-(2,6-dimethylphenyl-N-methylamidino)ure
                                 a                        7               
+ conc. HCl                                                               
1-(2-trifluoromethyl-4-chlorophenyl-N-methylamidino)-3-t-                 
                                 1-(2-trifluoromethyl-4-chlorophenyl-N-met
                                 hylamidino)-             7               
butylurea + conc. HCl            urea                                     
1-(2-methyl-4-trifluoromethylphenyl-N-methylamidino)-3-t-                 
                                 1-(2-methyl-4-trifluoromethylphenyl-N-met
                                 hyl-                     7               
butylurea + conc. HCl            amidino)urea                             
1-(2,4-dichloro-6-methylphenyl-N-methylamidino)-3-t-butylurea             
                                 1-(2,4-dichloro-6-methylphenyl-N-methylam
                                 idino)urea               7               
+ conc. HCl                                                               
1-(2,6-dichloro-4-methylphenyl-N-methylamidino)-3-t-butylurea             
                                 1-(2,6-dichloro-4-methylphenyl-N-methylam
                                 idino)urea               7               
+ conc. HCl                                                               
1-(2-chloro-4-methyl-6-fluorophenyl-N-methylamidino)-3-t-butyl-           
                                 1-(2-chloro-4-methyl-6-fluorophenyl-N-met
                                 hylamidino)-             7               
urea + conc. HCl                 urea                                     
1-(2,6-dimethyl-4-chlorophenyl-N-methylamidino)-3-t-butylurea             
                                 1-(2,6-dimethyl-4-chlorophenyl-N-methylam
                                 idino)urea               7               
+ conc. HCl                                                               
1-(2,6-dimethyl-4-fluorophenyl-N-methylamidino)-3-t-butylurea             
                                 1-(2,6-dimethyl-4-fluorophenyl)-N-methyla
                                 midino)urea              7               
+ conc. HCl                                                               
1-(2,4,6-trichlorophenyl-N-methylamidino)-3-t-butylurea                   
                                 1-(2,4,6-trichlorophenyl-N-methylamidino)
                                 urea                     7               
+ conc. HCl                                                               
1-(2-chloro-4-methyl-6-fluorophenyl-N-methylamidino)-3-t-butyl-           
                                 1-(2-chloro-4-methyl-6-fluorophenyl-N-met
                                 hylamidino)-             7               
urea + conc. HCl                 urea                                     
1-(2,4-dimethyl-6-chlorophenyl-N-methylamidino)-3-t-butylurea             
                                 1-(2,4-dimethyl-6-chlorophenyl-N-methylam
                                 idino)urea               7               
+ conc. HCl                                                               
1-(2,4-dimethyl-6-fluorophenyl-N-methylamidino)-3-t-butylurea             
                                 1-(2,4-dimethyl-6-fluorophenyl-N-methylam
                                 idino)urea               7               
+ conc. HCl                                                               
1-(2-chloro-4-fluoro-6-methylphenyl-N-methylamidino)-3-t-                 
                                 1-(2-chloro-4-fluoro-6-methylphenyl-N-met
                                 hylamidino)-             7               
butylurea + conc. HCl            urea                                     
1-(2,6-dichloro-4-fluorophenyl-N-methylamidino)-3-t-butylurea             
                                 1-(2,6-dichloro-4-fluorophenyl-N-methylam
                                 idino)urea               7               
+ conc. HCl                                                               
2-methyl-4-chlorophenylguanidine + piperidinoyl chloride                  
                                 1-(2-methyl-4-chlorophenylamidino)-3,3-pe
                                 nta-                     10              
                                 methyleneurea                            
2-methyl-4-chlorophenyl-3-methylguanidine + methylisocyanate              
                                 1-(2-methyl-4-chlorophenylamidino)-1,3-di
                                 methylurea               6               
2-chloro-4-methylphenyl-3-methylguanidine + methylisocyanate              
                                 1-(2-chloro-4-methylphenylamidino)-1,3-di
                                 methylurea               6               
2-methyl-6-chlorophenyl-3-methylguanidine + methylisocyanate              
                                 1-(2-methyl-6-chlorophenylamidino)-1,3-di
                                 methylurea               6               
1-(2,4,6-trichlorophenyl-1,2,3-trimethyl-3-(N,N-pentamethylene-           
                                 1-(2,4,6-trichlorophenyl-N,N&#39;-dimethylami
                                 dino)-1-                 9               
carbamyl)thiouronium iodide + methylamine                                 
                                 methyl-3,3-pentamethyleneurea            
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