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Patented Apr.‘ '24, 1945 2,374,335 _~ UNTED STATES ' PATENT OFFlCE 2,374,335‘ ' TRIAZOLE DERIVATIVES Gaetano F. D’Alelio, Pitts?eld, Mass.,'assignor to General ‘Electric Company, a corporation of New York 1 No Drawing. Application December 26, 1942, Serial No. 470,220 , (oi. 260-308) 14 Claims. > where R, R’ and Z have the same meanings as given above with reference to Formula I. tives. The invention especially is concerned with I Illustrative examples of divalent radicals that the production of new and useful acylaminoaryl Z in the above formulas may represent are: di amino triazoles. ' ' 5 valent aromatic, e. g., phenylene, xenylene, naph This invention relates to new chemical com pounds and more particularly to triazole deriva thylene, etc.; divalent aliphatic-substituted aro matic, e. g., 2,4-tolylene, ethyl 2,5-phenylene, iso The triazole derivatives of this invention may be represented by the following general formula: propyl 3,4-phenylene, l-butyl 2.,4-naphthylene, 1,4-dimethyl 2,3-phenylene, etc.; radicals that - - 10 may be classed either as divalent aliphatic-sub stituted aromatic or as divalent aromatic-sub stituted aliphatic and wherein the-free bond of where R represents a member of the class con-'7 the aromatic nucleus is attached to the acylamino sisting of hydrogen and monovalent hydrocarbon radical, e. g., 4,alpha-tolylene, 3,beta-phenylene radicals, R’ represents a monovalent hydrocarbon 15 ethyl, 4,alpha-xylylene, 2,gamma-phenylenebutyl, radical, and Z represents a member of the class etc. ; and their homologues, as well as those .di-_ valent radicals with one 'or_-more of their nuclear consisting of divalent aromatic and nuclearly 'sub-A stituted, more particularly nuclearly halogenated, hydrogen atoms replaced by a substituerit, e. en, acyl, allgvl, alkenyl, hydroxy, alkoxy, aryloxy, Illustrative examples of monovealent hydrocar-v 2o carboalkoxy, carboaroxy, sulfamyl, an acylamino aromatic hydrocarbon radicals. ' bon radicals that R and R’ in the above formula may represent are: aliphatic (e. g., methyl, ethyl, emit-r’) propyl, isopropyl, butyl, secondary butyl, isobutyl, butenyl, amyl, isoamyl, hexyl, octyl, allyl, meth grouping in addition to the single acylamino allyl, crotyl, etc), including cycloaliphatic (e. g" grouping shown, for example, in Formula I, etc.' cyclopentyl, cyclopentenyl, cyelohexyl, cyclo 25 ‘Specific examples of substituted divalent radicals hexenyl,‘ cycloheptyl, etc.); aryl (e. g., phenyl, di that Z may represent are chlorophenylene, bromo-v phenyl or xenyl, naphthyl, anthracyl, etc); phenylene, chloroxenylene, chloronaphthylene, aliphatic-substituted aryl (e. g., tolyl, xylyl, ethyl ' chlorotolylene, bromotolylene, ethoxyphenylene, ' phenyl, propylphenyl, isopropylphenyl, allylphen actophenylene, actoxyphenylene, aminophen yl, z-butenylphenyl, propenylphenyl, tertiary 3° ylene, carboethoxyphenylene, sulfamylphenyl butylphenyl, methylnaphthyl, etc.); and aryl ene, carbophenoxyphenylene, hydroxyphenylene', substituted aliphatic (e. g.', benzyl, cinnamyl, phenoxyphenylene, methylphenylene (tolylene), 'phenylethyl, phenylpropyl, etc.) . Preferably R allylphenylene, etc.’ Preferably Z is phenylene or represents hydrogen, in which case the com pounds correspond to the following general 35 tolylene. ' ‘ ' The new compounds of this invention may be used, for example, as pharmaceuticals, insecti 4 - cides, fungicides, plasticizers and as intermediates in the preparation of‘ derivatives thereof, e. g., 40 ureido, ‘acyl, hydrazino, ‘carbamyl, amidine, methylol, methylene, etc., derivatives of them _ where Z and R’ have the same meanings as given dividual compound embraced by Formula I, These above with reference to Formula I. However, ‘there also may be produced in accordance with the new compounds are especially valuable in the present‘ invention chemical compounds , corre sponding to the following general formulas: III '- ‘N—-N—R ‘ ‘ preparation of synthetic resinous ;compositions.. 45‘ Thus, they may be condensed’ with, for instance, aldehydes, including- polymeric aldehydes, hy droxy-aldehydes and/aldehyde-addition products, to yield condensation products having particular utility in the plastics and coating arts.' Such IV 50 condensation products are more fully described and are speci?cally claimed in my copending all plication Serial‘ No. 470,219, ?led concurrently herewith and assigned to the same assignee as the present invention. 66 . , Various methods may be employed‘ to produce 2 2,374,335 Ethyl hydrazine Propyl hydrazine Isobutyl hydrazine Phenyl hydrazine Allyl hydrazine Propenyl hydrazine Cyclohexyl hydrazine Tolyl hydrazines Xylyl, hydrazines Phenethyl hydrazine Ethylphenyl hydrazines Octyl hydrazine Naphthyl hydrazines the chemical compounds of this invention. I pre fer to prepare them by effecting reaction under ‘heat between a hydrazine corresponding to the ‘ general formula - where R has the'same meaning as given above with reference to Formula -I, and an acylaminoaryl biguanide corresponding to the general formula VI NE NH _ 0 ‘ NH,-<l§-Nn_t|:-NH-z_NR-t'J-R' where R, R’ and Z have the same-I meanings as given above with reference to Formula. I. This Illustrative examples of acylaminoaryl bi reaction is carried out under conditions such as 15 guanides that may be employed, depending upon will result in the formation of ammonia, or, if the particular end-‘product desired, are: an acid is present, an ammonium salt as a by product of the reaction. This reaction may be Acetylaminophenyl biguanides (acetamidophenyl represented by the following general equation: :20 biguanides), including ortho-(acetylamino) phenyl biguanide, meta-(acetylamino) phenyl biguanide and para-jacetylamino) phenyl bi guanide ' *Acetylaminotolyl biguanides, which may be rep resented by the formula 25 Or, when the reaction is carried out in. the IX presence of an acid effective in binding the am monia liberated during the reaction, it may be represented by the following general equation: 30 Acetylaminoxylyl biguanides Acetylaminonaphthyl biguanides 35 Acetylaminoxenyl biguanides, which may be rep resented by the formula ‘ Fox) 1 In Equations VII and VIII, R,‘ R’ and Z have _ 40 the same meanings as given above with refer ence to Formula I, and HA (Equation VIII) represents an acid, which may be either or ganic. orv inorganic but which preferably is in organic. Illustrative examples of organic and 45 inorganic acids that may be used to bind the ammonia in the form of a salt are oxalic, acetic, hydrochloric, hydrobromic,_ sulfuric, etc. -The reaction advantageously is carried out in an aqueous solution containing an inorganic‘ acid. 50 However, other solvents or mixtures of solvents or by the formula 0 XI- I|~IH I|\|IH 7 (QNH- ill -cH, . H,N-d-NH-c-Nn-< ' > may be used, e. g‘.,"a1c0h01s, ethers, dioxane, benzene, etc. The reaction may be carried out under a variety of temperature and pressure 'con- . ditions. Ordinarily the ‘reaction is e?ected at 55 Propanoylaminophenyl biguanides Butanoylaminophenyl biguanides Bu'tanoylaminotolyl biguanides atmospheric pressure under re?ux at the boil- . ‘ Isobutanoylaminoxylyl biguanides Propenoylaminophenyl biguanides ing temperature of the reaction mess. The acid represented by HA in Equation VIII may constitute one of the starting materials, to Propenoylaminonaphthyl biguanides ' ' Cyclopentanoylaminophenyl biguanides gather with the hydrazine and the acylaminoaryl 60 vBenzoylaminophenyl biguanides biguanide. Or, if desired, the acid may be in troduced into the reaction mixture in other Acetylamino-(chloro)~-phenyl biguanides, which , may be represented by the formula. forms. For example, a Part of the acid may be employed in a free or solution state and a. part in the form of a‘ mono salt of the acylaminoaryl 65 biguanide or of the hydrazine; or, a part ‘of the acid may be used in the form of a mono salt of the hydrazine and a part in the form of a mono salt of the acylaminoarylbiguanide. ' ‘ Illustrative examples of hydrazines that vmay be used, depending upon the» particular end product desired, are: \ V - _ __ I Hydrazine (or hydrazine hydrate) Methyl hydrazine _ = 1' Acetylamino-(bromo) -phenyl biguanides Propanoylamino-(chloroT-tolyl biguanides Acetylamino- (iodo) -phenyl biguanides ,Acetylamino- (?uoro) -p_henyl biguanides " 3v Toiuylaminoxenyl biguan'ides,_ which may be represented by the formula (Para-acetamido phenyl) biguanide hydro chloride I - ‘- ' 135.2 Hydrazine hydrate (in 34.5 parts water)-.. 25.0 v Concentrated aqueous solution of hydro ,chloric acid (approx.'38% HCl) _____ __ OH; XIII 48.0 Water 200.0 were heated together under reflux at the‘ boil ' ing temperature of the massfor 18 hours, after or by the formula which the solution was evaporated to dryness-to yield a gummy. semi-crystalline mass. This mass was dissolved in boiling ethyl alcohol. The on, Us“? alcohol-insoluble material, mostly ammonium chloride, was removed vby ?ltration. 'I'he.?ltrate 15 was vtreated with ’a de-colorizing carbon to de— colorize it.» after which it was concentrated by evaporation.‘ While still hot, ether was added vto the concentrated‘?ltrate until a solid bezan to precipitate from the solution. The solution (N-methyl acetylaminophenyl) biguanides . (N-ethyl , propanoylai‘nino ethylphenyl) guanides ‘ 20 was chilled to obtain a maximum yield of (N-isobu'tyl benzoylamino methylnaphthyl) bi guanides _ p . — ~- . ,solid precipitate comprising (para-acetamido ‘ anilino) amino 1.2,4-triazoles. The product was removed from the solution by ?ltration and dried. The dried material had a melting point of about 200° _C. with some indication of decomposition at (N-cyclopentyl benzoylamino phenyl) bizu'anides' (N-phenvl methylcyclopentanoylamino chloro-. phenyl) biguanides, which may be‘ represented by the formula v ‘ this temperature. ‘ The corresponding‘ortho and meta derivatives are‘ prepared by using 135.2 parts of (oi-tho; acetamido phenyl) bi'guanide- hydrochloride o'r (meta-acetamido phenyl) biguanide Mal-'0', 30 chloride instead of 135.2 parts of (para. acetamido phenyl) biguanidev hydrochloride. I _1,2,4-triazoles' are ‘prepared in essentially'the - (N-xenyl acetylamino bromotolyl) biguanides, same manner as described under Example 1 with which may be represented by the formula j xvi the exception that 23 parts of methyl hydra ‘ zine are used in place of 25 parts of hydrazine . - II Example 2 'l-methyl (para-acetamido anilino) amino 35 hydrate. If?“ ' Example 3 l-phenyl _(para-acetamido anilino) amino 1,2,4-triazoles are prepared in essentially the 45 same‘manner as described under Example 1 .with the exception that 54 parts of phenyl hy drazine ‘ are ‘used instead of 25 parts of hydra zine hydrate.v , I ' ' p Example 4 ('Para-propanamido anilino) amino l.2,4¢tri . azoles are produced in essentially‘ the same man ner_- as ‘described under Example 1 withthe ex Ethylbenzoylaminophenyl biguanides. ception that 142.2 parts of (para-p'ropanamido V 'phenyl) ‘biguanide hydrochloride, which alsom'ay The acylaminoaryl'biguanides used in practic- ’ ‘ ing the present invention are prepared, for exam . be named (para-propanoylamino phenyl) bigua- nide of hydrochloride, are used in place of 135.2 ple, by e?ecting reaction between biguanide or di- - . parts of (para-acetamid'ophenyl)“ biguanide hy- . cyandlamide ~(cyanoguanidine) and an acyl aminoaryl amine, ‘preferably in the presence of an inorganic acid. .In order that those skilled in ‘the .art better ' may understand how- the'present invention may be carried into e?ectgthe following examples are given by way ofa'illustration and not by way oi’ limitation. All part/‘fare by weight. ' ‘' ,Era'mple 1 drochloride.. ' 60 r a , Example _5 1 same manner as described under Example 1 with the exception that 142.2 parts of »[(N'-methyl para-acetamido)_ phenyl] biguanide ,hydroohlo-f ride are used instead-oi‘ 135.2 parts or‘ (para acetamido phenyl) I biguanide hydrochloride. amino 1,2.4-triazoles, 'More speci?c examples of compounds ‘embraced by Formula I that may beproduced in accordance which also may be named (para-acetylamino with the present, invention arelisted below: phenvlamino) amino 1.2, __.-t1_'iazoles,. oriv'(para acetylamino‘ anilino). amino.v 1,2,4-triazoles, or l-metl'rvl. (ortho-acetamido anilino) amino 1,2,4 (para-acetamido .phenylamino') 1 ‘amino 1,2,4_-tri azoles.v . [(N-methyl 'para-aceta‘mido) anilino] a' o 1,2,4-triazoles are prepared in essentiall the This example illustrates the preparation of v ' (paraacetamido anilino) ‘ . ‘ . triazoles . ' ' , ' - ,l-methyl (meta-acetainldo anilino) amino 1,2,4 ' 175' t'riazoles 2,374,836 4 L-prepyl (acetamide toluide) amine 1,2,4-tri l-phenyl (ortho-acetamido aniline) amino 1,2,4 triazoles' azeles I triazoles ' - l-isebutyl (benzamide'aniline) amine 1,2,4-tri l-phenyl (meta-acetamide aniline) amine 1,2,4 azoles l-propenyl (benzamido aniline) amino-1,2,4-tri , (Orthe-propanamido aniline) amino 1,2,4-trl azoles > azoles, which may be represented by the ter- . . l-cyclopentyl (acetamido aniline) amino 1,2,4 mula triazoles XVII 10 L \Ni - 1~pheny1 (methylbenzamido xylidine) amino 1,2,4-triazoles l-methyl [(N-methyl acetamide) aniline] amine 1,2,4-triaz‘oles, which may be represented by the formula _ - (Meta-prepanamido aniline) amine 1,2,4-tri azeles _ (Acetamido teluide) amine 1,2,4-triazoles, which may represented by the formula 20 vl-benzyl ['(N-ethyl acetamide)‘, aniline] amine 1,2,4-triazeles (Acetamide chlero aniline) amino 1,2,4-triazoles (Acetamido bremo aniline) amine 1,2,4-triazeles 25 l-ethyl (acetamido aniline) amino 1,2,4-triazoles l-methyl (acetamido teluido) amino 1,2,4-tri azoles ' triazoles - 30 ' (Propanamido toluide) amine 1,2,4-triazeles (Butanamido teluido) amino 1,2,4-triazeles XIX CH; mg triazeles I [(N-phenyl acetamide) aniline] amino 1,2,4-tri azeles v . [(N-ethyl prepanamido) aniline] amine'1,2,4-tri (Isebutanamido -xylidino) amino 1,2,4-triazoles, which may be represented by the formula _ l-ethylphenyl (acetamido aniline) amino 1,2,4 l-phenyl (acetamide vteluido) ‘amino 1,2,4-tri azeles (Prepanamido iode toluide) amine 1,2,4-triazeles (Butanamide ?uere toluido) amine 1,2,4-triazeles l-phenethyl (acetamido aniline) amine 1,2,4 azoles - 85 [(N-prepyl butanamido) teluide] amine 1,2,4 triazoles, which may beg-represented by thefor CH; mula ' (Prepenamido 'naphthylamino) amino 1,2,4-tri azoles (Cyclopentanamido xenylamino) amino 1,2,4-tri 45 [(N-isebutyl I benzamido) azeles (Hexahydrobenzamido aniline) amino 1,2,4-tri azeles [(N-cyclepentyl acetamide) aniline] amino 1,2,4 > (Benzam'ide toluido) amino 1,2,4-triazeles (Toluamido aniline) amine 1,2,4-triazoles (Toluamido teluide) amine 1,2,4-triazeles 50 azeles 1,2;4-triazoles l-methyl [(N-methyl acetamido) naphthylami (‘3111s no] amino 1,2,4-triazeles | lNHC> I 0-‘ I \ ¢ N I _ ' ~ NB-(?-OH; ‘ ' .0 1,2,4-tria2eles 60 1,2,4-triaze1es (Dimethylbenzamido ?uore aniline) amine 1,2,4 _ . ‘ It will be understood, of course, by those skilled 65 mula XXI amine 1,2,4-triazoles l-ethyl [(N-phenethyl acetamido) toluido] amine l-allyl (acetamido aniline) amineLZA-triazeles ~ triazoles, which may be represented by the for- \ l-telyl [,(N-benzyl acetamido) propyl aniline] (Benzamido methyl naphthylamine) amino 1,2,4 , triazoles , l-phenyl [(N-phenyl acetamide) aniline] amine I N———-N—H -e ' l-methyl [(N-phenyl acetamide) aniline] ‘amide which may be represented by the formula H:N——[ I triazoles [(N-telyl acetamide) toluidol' amino 1,2,4-tri» ' (Acetamido ethyl aniline) amino 1,2,4-triazeles, L amine [(N-phenyl benzami'do) aniline] amine 1,2,4ltri (Benzamide aniline) amine 1,2,4-triazeles azeles xenylamino] 1,2,4-triazoles in the art that in the'compounds listed above the amine grouping may be attached to either the 3 or the 5 carbon atom of the triazele nucleus, the carbon atom which is not joined to an amine . grouping being attached to the aeylaminoaryl amino grouping; and’, also, that the acylamine grouping may be attached to any of the reactive N carbon atoms of the aromatic nucleus. ‘ What I claim as new and desire to, secure by (Naphthamide aniline) amino 1,2.4Ftr1azo1es 75 Letters Patent of the United States is: - 5 2,374,935 ’ where R’ represents an alkyl radical and Z rep 1. Chemical compounds corresponding to the resents 'a divalent aromatic hydrocarbon radical. general formula V '7. Chemical compounds corresponding to the general formula ‘ where R represents a member of the class con \ % N sisting of hydrogen.'and monovalent hydrocarbon where R’ represents an alkyl radical and Z rep resents a phenylene radical. . radicals, R’ represents a monovalent, hydrocarbon radical, and Z represents a member of the class consisting of divalent aromatic and nuclearly a. (Ortho-acetamido anilino) halogenated aromatic hydrocarbon radicals. 2. Chemical compounds corresponding to the general formula triazoles. amino 1,2,4; v 9. (Meta-acetamido anilino) amino 1,2,4 10. (Para-acetamido 'anilino) amino 1,2,4 15 triazoles. ‘ triazoles. ' ' 11. The method of preparing chemical ‘com pounds corresponding to 'the general formula where R represents a member of the class con 20 sisting of hydrogen and monovalent hydrocarbon radicals, R’ represents a monovalent hydrocarbon ' radical, and Z represents a divalent aromatic hy drocarbon radical. where R represents a member of the class con - sisting of hydrogen and monovalent hydrocarbon 3. Chemical compounds corresponding to the general formula ' radicals, R’ represents a monovalent hydrocarbon‘ radical, and Z represents a member of theclass - consisting of divalent aromatic and nuclearly> halogenated aromatic hydrocarbon radicals, said method comprising effecting reaction under heat between a hydrazine corresponding to the general where R represents a member of the class con sisting of hydrogen and monovalent hydrocarbon I formula radicals, R’ represents a monovalent hydrocarbon radical, and Z represents a divalent aromatic hy where R has the meaning above given, and an drocarbon radical. 4. Chemical compounds corresponding to the general formula general formula _ ' ac'ylaminoaryl biguanide corresponding ‘to the NH ' NH . o NHi-g-—NH—g-NH—z-NR—<|i-R' where R, R’ and Z have the meanings above given. 12. A method as in claim 11 wherein the re action is carried out in the presence of an acid effective in binding the ammonia liberated during where R’ represents a monovalent hydrocarbon radical and Z represents a divalent aromatic hy 45 the reaction. 13.. The method of preparing (para-acetamido drocarbon radical. . anilino) amino. 1,2,4-triazoles which comprises 5. Chemical compounds corresponding to the effecting reaction under heat between (para acetamido phenyl) biguanide and hydrazine hy general formula 50 drate in the presence of an acid effective in bind ing the ammonia liberated during the reaction. whcre R’ represents a monovalent hydrocarbon 55 radical and Z represents aphenylene radical. 6. Chemical compounds corresponding to the general formula 14. The method of preparing (para-acetamido anilino) amino 1,2,4-triazoles which comprises e?'ecting reaction under heat between (para acetamido phenyl) biguanide hydrochloride and hydrazine hydrate, the said reaction being carried out in an aqueous solution containing hydro chloric acid in an. amount su?icient to bind the ammonia liberated during the reaction. GAETANO F. D’ALELIO. CERTIFICATE OF CORRECTION. Patent No. 257L555. April 21;, 19Li5. GAE'I‘ANO F. D'ALELIO. It is hereby certified that error appears in the printed specification of the above numbered patent requiring correcti on as follows: Page 1, first column, line 50, between formula III and formula IV insert the word "and"; and second column, line 50, for "actophenylene, actoxyphenylene" read —-acetophenylene, acetoxyphenylene--; page 5, first column, lines 27 to 57 inclusive, for that portion of the formula readingv "H511" read —-H2N--; and second column, line 57, after the syllable "nide" strike out "of"; page 14., second column, line 19, for "H20" read —-H5C-—; line 55, for "amido" read —-amino——; and that the said Letters Patent should be read I with this correction therein that the same may conform to the record of the case in the Patent Office. Signed and sealed this 10th day of July, A. D. 1911.5. Leslie Frazer (Seal) Acting Commissioner of Patents.