Patent GB-794398-A (GB)
Title: Method of producing n-substituted products of 2,4-diamino-1,3,5-triazine
IPC: C07D251/18
Filed: 1956-07-11
Abstract: N - substituted 2 : 4 - diamino - 1 : 3 : 5-triazines of the formula: <FORM:0794398/IV (b)/1> wherein R1, R2, R3 and R4 may be the same or different and represent hydrogen, alkyl, aryl, substituted aryl or a heterocyclic radical, are prepared by heating with formic acid a salt of a biguanide of the formula: R1R2N-C(NH)-NH-C(NH)-NR3R4 and a volatile inorganic acid such as hydrochloric or hydrobromic acid. Specified heterocyclic radicals are piperidyl, pyridyl, pyrimidyl, chinolyl, pyrryl, furyl and thiazolyl.  The diaminotriazine derivative may be precipitated as the free base or as an acid addition salt by respective addition of dilute alkali or dilute acid to the completed reaction mixture.  The examples describe the preparation of N-ethyl - 2 : 4 - diamino - 1 : 3 : 5 - triazine, N - phenyl - 2 : 4 - diamino - 1 : 3 : 5 - triazine, N - para - toluyl - 2 : 4 - diamino - 1 : 3 : 5-triazine hydrochloride, N - para - chlorophenyl - 2 : 4 - diamino - 1 : 3 : 5 - triazine hydrochloride and hydrobromide and N-paranitrophenyl - 2 : 4 - diamino - 1 : 3 : 5 - triazine. Specification 676,024 is referred to. condensing agent, or by reacting a 5,6-dihydrobenzo (c) cinnoline of the general formula: <FORM:0794398/IV (b)/2> wherein R1 and R2 have the above significance, or an N-acyl derivative thereof, with a malonic acid diester of the general formula: <FORM:0794398/IV (b)/3> wherein X represents the residue of a hydroxyl compound, in the presence of an alkaline condensing agent, or with a malonic acid derivative of the general formula: <FORM:0794398/IV (b)/4> wherein R has the above significance and Y represents a chlorine or bromine atom or an acyloxy radical, in the presence of an acid binding agent, or with a malonic acid derivative of the general formula: <FORM:0794398/IV (b)/5> wherein R, X and Y have the above significance in the cold to form an N-(a -carbalkoxyacyl)-dihydrobenzocinnoline of the general formula: <FORM:0794398/IV (b)/6> wherein R, R1, R2 and X have the above significance, which is then reacted with an alkaline condensing agent, or in the case where R is other than hydrogen, by reacting an N,N1-malonyl-dihydrobenzocinnoline of the general formula: <FORM:0794398/IV (b)/7> wherein R1 and R2 have the above significance, with an organic oxo compound of the general formula R1 = O, wherein R1 represents the geminate divalent radical corresponding to the R radical and has, therefore, one hydrogen atom less, and simultaneously or subsequently reacting the resulting N,N1-(unsaturated substituted malonyl) - 5,6 - dihydro - benzo (c) cinnoline of the general formula: <FORM:0794398/IV (b)/8> with catalytically activated hydrogen, e.g. hydrogen in the presence of hydrogen activated noble metal catalysts or Raney nickel.  Suitable alkaline condensing agents are alkali metals and compounds thereof such as alcoholates, amides and hydrides. Suitable acid binding agents are tertiary organic bases such as pyridine, dimethylaniline and triethyl- and tributylamine. Suitable malonic acid diesters and substituted malonic acid diesters mentioned are the dimethyl and diethyl esters of malonic acid and of the following monosubstituted malonic acids: methyl, ethyl-, n- and iso-propyl-, n-, iso-, sec.- and tert.-butyl-, n- and iso-amyl-, n-hexyl-, n-heptyl-, n-octyl-, b -ethylhexyl-, decyl-, dodecyl-, cetyl-, octadecyl-, allyl-, crotyl-, methallyl-, octadecenyl-, b -methoxyethyl-, b -ethoxyethyl-, b  - n - butoxyethyl -, b  - methylmercaptoethyl-, b  - isopropylmercaptoethyl -, g  - methylmercaptopropyl -, b  - dimethylaminoethyl -, b -diethylaminoethyl -, cyclopentyl -, cyclohexyl-, cycloheptyl -, cyclohexenyl -, 2,5 - endomethylene - D 3 - cyclohexenyl -, 2,5 - endomethylene-D 3 - cyclohexenylmethyl -, benzyl -, p - chlorobenzyl -, m,p - dichlorobenzyl -, p - bromobenzyl -, p - methoxybenzyl -, b - phenylethyl-, g  - phenylpropyl -, cinnamyl -, b  - phenoxyethyl -, b  - phenylmercaptoethyl -, g  - phenylmercaptopropyl -, phenyl -, p - chlorophenyl-, m,p - dimethylphenyl -, p - methoxyphenyl, furly - (2) -, furfuryl - (2) -, tetrahydrofurfuryl-(2) -, d  - tetrahydropyraryloxy - (2) - butyl -, g ,g  - ethylenedioxybutyl -, thienyl - (2)-, thenyl -, pyridyl - (2) -, pyridyl - (4) -, a -picolyl -, g  - picolyl -, b  - pyridyl - (4) - ethyl-, b  - pyrrolidinoethyl -, b  - piperidinoethyl-, indolyl - (3) - methyl -, 1 - methyl - indolyl - (3)-methyl -, quinolyl - (2) - methyl -, quinolyl - (4)-methyl -, b  - morpholinoethyl -, b  - (4 - methylpiperazino)ethyl -, g  - pyridyl - (2) - mercaptopropyl - and g - benthiazolyl - (2) - mercaptopropyl - malonic acids.  Examples of 5,6 - dihydro-benzo (c) cinnoline which may be used as reactants are 5,6-dihydro-benzo (c) cinnolines, 1,10 - dimethyl - 5,6 - dihydrobenzo (c) cinnolines, 2,9 - dimethyl - 5,6 - dihydro - benzo (c) cinnoline, 3,8 - dimethyl - 5,6 - dihydrobenzo (c) cinnoline 3,8 - dichloro - 5,6 - dihydrobenzo (c) cinnoline and 3-bromo-5,6-dihydrobenzo (c) cinnoline.  Suitable oxo compounds of the general formula R1 = O mentioned are acetaldehyde, butyraldehyde, enanthaldehyde, crotonaldehyde, b  - methoxypropionaldehyde, benzaldehyde, phenyl acetaldehyde, b -phenyl propionaldehyde, cinnamic aldehyde, furfural, nicotinaldehyde, isonicotinaldehyde, acetone, butanone, cyclopentanone, cyclohexanone, cycloheptanone and acetophenone. A number of detailed examples are given, the reactants used being included in the lists referred to above.