Патент USA US2403790код для вставки
Patented July 9, 1946 ' ‘2,403,790 UNITED STATES, PAT ENT 'iOF-FICE ’ 12,403,790 METHOD ‘OFIPREPARING , ‘DIAzIN-E ‘V DERIVATIVE ' Gaetano F. DfAlelio and James:wp?iierwota; Pitts?eld, Mass, 'as'signors : “"Géiiéial Elec- " ' tric Company, a corporatior'iof New York‘ , No Drawing‘... Application September I, 1942, - 7 Serial No. 456,929 ' c 1 Claim. (01. 2604451’) 2 This invention relates, to the preparation’ of ‘- one'o'r more of their hydrogen atoms substituted diazine derivatives-Which: areembraced by the‘ by, for example, a halogen, .more particularly following general formula: chlorine, ‘bromine, ?uorine or iodine. Speci?c I . , ' ' 1 C\ ll 0 N V V -. A In the above formula 12 represents an integer-arid is at least I- and not more ‘than 2,-R1representsa' ' member, of the class consisting of hydrogen ‘and monovalenthydrocarbon and substituted hydro-~ V :ITL-GNI‘HRM examples of halogeno-substituted hydrocarbon radicals that R in. the’ above formula may rep resent are: chloromethyl, chloroethyl, chloro phenyl, dichlorophenyl, ethyl chlorophenyl, ch10 carbon-radicals, more particularly halo-hydrocar= 15 rocyclohexyl, phenyl-r chloroethyl, bromoethyl, I bon radicals, and Z represents a member of the bromopropyl, \?‘uorophenyll, liodophenyl, \bromo class consisting of oxygen and sulfur. Morer'par ticularly the invention is concerned with ‘certain toly'l,‘etc. ' .Preferab-ly'R 'is hydrogen. ‘ However, there also may be ‘produced in» accordance with new and useful improvements in a-method of the present invention compounds such, for in Illustrative examples of radicals that R in For- ' Where n (Formula II), R and Z (Formulas II, III mula I may represent are: aliphatic (e. g;, methyl, I 45 and IV) have the same meanings as v ethyl, propyl, isopropyl, butyl; 's’econdary‘but'yl, isobutyl, butenyl, amyl, isoamyl, 'hexyl', etc.),"'iri-‘ eluding cycloaliphatic (e; g., cyclopentyl,‘ cycloe" pentenyl, cyclohexyl; jcyclohexenyl, cycloheptyl, etc.) ; aryl (e. g.,'phenyl, diphenyl or Xenyl, naph with reference to Formula I. given above c h ' The compounds embraced by Formula I maybe used, for example, as pharmaceuticals; plasti cizers,fungicides, bactericides, insecticides,»_a_s ad ditives to petroleum products, as an intermedi thyl, etc.); aliphatic-substituted‘ aryl (e. g.,.toly1, 50 ate in the preparation of dyes, drugs, textile as xylyl, ethylphenyl, propylphenyl, isopropylphenyl,“ sistants and other chemical compounds, for in allylphenyl, Z-butenylphenyl, tertiary-butylphen stanc'e‘as .an intermediatein- producing deriva yl, etc.) ; aryl-substituted aliphatic (e. g., benzyl, tives thereof such asureido, hydrazine, carbainyl, cinnamyl, phenylethyl, phenylpropyl, etc.) ; and. amidine,=inethylol, methylene, ‘etcl, derivatives of their?homologueai as well as those groupsiwithr 55 --the individual compound represented byrtrmina 2,403,790 l4 , 3 2-mercapto 4,6-di-cyc1opentylamino) 5-ethyl py I. These compounds are especially valuable in the preparation of synthetic resinous composi tions. rimidine 2-mercapto 4,6-dianilino pyrimidine Z-mercapto 4,6-ditoluido 5-iodophenyl pyrimi Thus, they may be condensed with, for example, aldehydes, including polymeric alde hydes, hydroxyaldehydes and aldehyde-addition products to yield condensation products having dine 2-mercapto 4,6-dixy1idino pyrimidine 2-mercapto 4,6-di-(phenethylamino) particular utility in the plastics and coating arts. Such condensation products are more fully de _ ' - 2-mercapto scribed and are speci?cally claimed in our co 10 pending application Serial No. 461,770,1‘iled Oc tober 12, 1942, and assigned to the same assignee 5-butyl pyrimidine 4,6-di-(ethy1phenylamino) 5-tolyl pyrimidine‘ ' ‘4-mercapto 2,6-di-(methylamino) 5-methy1 py as the present invention. These compounds also rimidine v 2-mercapto ,.4,6-di<(chloroethylamino) pyrimi may be compounded with rubber, both natural and synthetic, to modify the propertiesfof the rubber.‘ Maine 7 For instance, they may be used to accelerate or I- _2-mercapto 4,6—di-(bromoxy1idino) 5-chloroethyl otherwise facilitate the vulcanization of natural 2-mercapto, 4,6-diamino 5-bromotoly1 pyrimidine pyrimidine and synthetic rubbers. Instead of using the com; ‘ < 2-mercapto 4,6-di-(iodoani1ino) pyrimidine pounds in the form shown in Formulall, they may be used in the form of their salts in such ap plications as above'mentioned by way of illus Z-mercapto 4-al1y1amino ?-butylamino pyrimi dine _ » ‘ 4-mercapto 2,6-di-(methylamino) pyrimidine tration. Z-mercapto 4,6-di-(methylamino) 5-methyl py Various methods may be employed to produce the chemical compounds embraced by Formula I. We prefer to prepare them by effecting reac rimidine ‘ ‘l-mercapto 2,6-di-(methy1amino) 5-pheny1 py tion, in the presence of a hydrohalide acceptor, between (1) a mercapto- diamino [(——NHR)2]_ pyrimidine corresponding to the general formula A g rimidine ‘ 2-mercapto 4-chloroethy1amino 6—methylamin0 pyrimidine ' 2-mercapto 4,6-dianilino 5-buty1 pyrimidine 2-mercapto 4-Xeny1amino 5-cyclohexenyl ?-ami . no pyrimidine 30 Z-toluidb 4-mercapto 5-cyclopenty1 ‘ti-amino py rimidine ~ - - v ‘ 7 I 2-mercapto 4,6-di-(propylamino) pyrimidine ’ 2-allylamino 4-mercapto ?-chloroanilino pyrimi Where R has the same meaning as given above with reference to Formula I and (2) a di-(halo alkyl) ether corresponding to the general formula VI XCnR27l'—Z-—C7LR21LX Where X represents a halogen atomyand n, Z dine - 2-penty1amino 4-mercapto S-phenyl G-amino py rimidine v 3 ‘ v ' 2-dichloroanilino 4-mercapto ‘5-toly1 ?-propyl amino pyrimidine v 2-cycloheptylamino é-mercapto G-butylamino py and R have the same meanings as given above rimidine with reference to Formula I, the reactants being Z-mercapto 4-(3’-butenylamino) ?-isopropylami employed in the ratio of at least two mols oi the mercapto diamino pyrimidine of (1) per mol of ‘ no pyrimidine It will‘be noted , ' Illustrative examples of di-(haloalkyl) ethers that when R in- Formula VI represents hydro- -> . that may be used, depending upon the particular end-product desired, are: the di-(haloalkyl) ether or (2). gen, the compound may be represented by the formula ‘ ' 1' Di- (chloromethyl) ether Di-(bromomethyl) ether Illustrative examples of mercapto diamino 50 ' Di- ( alpha-chloroethyl) ether > Di-(alpha-bro-moethyl) ether [(-NHR)2] diazines that may be employed, de pending upon the 'desired end-product, are: 1 ' Di-(beta-chloroethyl) ether ‘ _Di-_(beta-br0moethyl) ether n - 2-mercapto, 4,6 diamino pyrimidine 4-mercapto 2,6-diamino pyrimidine (G-mercapto ZA-diamino pyrimidine) 2-mercapto 4,6-diamino 5-methyl pyrimidine ll-mercapto 2,6-diamino 5-ethy1 pyrimidine Z-mercapto 4,6-diamino 5-pheny1 pyrimidine Z-mercapto é-bromotoluido G-benzylamino py-. Di-(beta-iodoethyl) ether Di-(alpha-chloroethyl) thioether 55 Di-(alpha-bromoethyl) thioether Di- (beta-chloroethyl) thioether _ Chloromethyl beta-chloroethyl ether Bromomethyl beta-bromoethyl thioether rimidine Di-(beta-gchloropropyl) ether 2-toluido ll-mercapto 6-methylamino pyrimidine _ 2-mercapto Ll-phenylchloroethylamino 6-phen ethylamino pyrimidine Z-mercapto e-chloroanilino G-phenethylamino pyrimidine 2-mercapto 4-cycloheptylamino ?-isopropylamino pyrimidine ' I 2-mercapto 4,6-di-(methylamino) pyrimidine Z-mercapto 4,6-di-(ethylamino) 5-?uorophenyl pyrimidine ' Z-mercapto 4,6-di-(?uoroanilino) pyrimidine Di-(beta-bromoethyl) thioether Di-(beta-bromopropyl) ether Di-(beta-chloropropyl) thioether Di-(beta-bromopropyl) thioether 65 . Di-(alpha-phenyl beta-bromomethyl) thioether Di-(a'lpha-phenyl beta-chloroethyl) ether Chloromethyl beta-chlorobutyl ether Chloromethyl beta-chlorobutyl thioether Di-(alpha-chlorobuten-3-Yl) ether Di-v(alpha-bromobuten-3-yl) thioether Various 1 hydrohalide' acceptors may be em ployed. We prefer to use a hydrohalide acceptor 2-mercapto ll-propenylamino G-amino pyrimidine that will react with the mercapto pyrimidine to Z-mercapto 4,6-di-(benzylamino) 5-_methyl py 75 form ‘a water-soluble salt. Examples of such ac- 2-mercapto 4-methylamino 6-amino pyrimidine rimidine ' - ' - 2303,7901'1 ceptors are the alkali=metalYhydroxides;e;1:5g.l» sodium hydroxide, potassium " hydroxide,. etc. Additional examples of hydrohalide acceptors . that may be used are other inorganic‘ bases; e; ign, calcium'hydroxide, barium hydroxide‘, ammonium temperature of the mass for 7 hours. ‘After 0001-: 7 ing', the dprecipitated‘ product comprising diethyl ether was‘ ?ltered off, washed well with water to remove s’oluble‘salts and dried.- ' ‘ A yield hydroxide, etc. ; carbonates of inorganic bases, in of 158parts'of the puri?ed and dried material cluding the carbonates of alkali metalsyorganic was obtained. No attempt was made to recover amines such as tertiary amines, e.- g.,;trimethyl any more product from the mother liquor. " . amine, dimethyltriethyl aniline,amine, quinoline, tributyl etc; amine,‘ quaternaryam pyridine, , Example 2 10" monium bases, e. g., tetrameth-yl ammonium'hy; .i I Beta,beta'-bis-(2,6-diamino pyrimidyl-4 thio): -, droxide, etc.; and the like. . .. . . diethyl ether, which also may be named his- ; [beta - (2,6 - diamino pyrimidyl-4 thio) ethyll The reaction between, the mercapto ‘diamino pyrimidine and the chosen‘ di- (haloalky-l') "ether ether, is' prepared in essentially the same manner may be carried out in any suitable manner,-but 15 as described under Example '1 with the exception, preferably is effected in a suitablesolvent or mix- . that 142 parts of é-mercapto 2,6-diaminopyrimii dine are used in place of 142 parts of 2-mercapto ture of solvents, e. g., water, alcohol, ether, ben 4,6-diamin'o pyrimidine. _ zene, dioxane, etc. Although. various solvents and solvent mixtures may be‘ employed, forlec'o nomic reasons and because of their eminent‘ suit 20 Beta,beta'-bis-(4,6-diamino pyrimidyl-2 thio) ability-we prefer tol use water or a mixture ‘of diethyl thioether’ is prepared in essentially the water and alcohol; Theereaction' maybe-car same manner as described under Example 1 with ried out undera variety of temperatureiandpres-q theyexception that 79.5 parts of di-(beta-chloro sure conditions, for instan'cefat' normal, sub-nor-' ethyl) thioether are used in place of '7la5parts‘of ' mal or at elevated temperatures and at'atmos'e-I di-"(beta-chloroethyl) ether. ' ph'eric, sub-atmospheric, ,oru supereatmospheric .. pressures. , ,. I . employ an alkali-metalhydroxide as the hydro- ' halide acceptor. ' WhenEa' non-aqueous solution constitutes the liquid medium in which the re - g ' ' ‘ ' v Beta,beta‘’-bis-(4,6-diamino pyrimidyl-Zl thio). ethyl isopropyl ether, which also may be named - beta-’(4,6-diamino pyrimidyl-Z thio) ethyl, beta-f (4,6-diamino pyrimidyl-Z . thio) isopropyl ether, action is effected, th'en it isusually desirableto employ a tertiary amine, e. g.,~pyridine', as them" drohalide acceptor. 3 Examjole 4 ' 7" When th'e~..reaction isicarried out .in ' an aqueous solution‘ it. is usually p‘referablefto Example is prepared in essentially the same manner as de scribed under Example 1 withthe exception that _ _. 78.5 parts of beta-chloroethyl beta-chloroiso - The above reaction maybe represented by the 35 propyl ether are used instead of 71.5 parts of di following general equationt' '. ‘ 1 (betaéc'hloroethyl) In- the above equation}; _:.re,presents1ar halogen.~ atom, and n, R and Z:have the same meanings a g. 1 50 given above with reference to Formula I5; _ ’ In order that those skilleddnI-the artxbetter. may understand how the present invention may This example illustrates the preparation .of diethyl ether, which‘ also may be named bis-"1 [beta 402,6 - diamino pyrimidyl-Z thio) ethyl] ' , _ Parts . Approx. mol ratio , Example 5' Beta,beta’-bis-[4,6-di - (methylamino) pyrim idyl-2' thio] diethyl ether is prepared in essen Vmercapto 4,6-di-(methylamino) pyrimidine are used in place of ‘142 parts of 2-mercapto 4,6-di amino pyrimidine. , beta,beta' - bis - (4,6-diamino -pyrimidyl'-2 thio) ether. ‘ ample 1 with the exception that 170 parts of 2 given by way of illustration. and not by way of. limitation. All parts, are by;weig~ht-. ' 7 tially thesame manner as described under Ex be carried into effect;the»following examples‘are , Example 1 '1 55 ether. ' ’ ' ' ‘ Example 6 1Beta,beta'-.bis-(4,6-diamino pyrimidyl-Z ' thio) to dipropyl ether, which also may be named .bis [beta-‘(4,6-diamino pyrimidyl-Z thio) propyll ether, is prepared in essentially the same manner as described under Example 1 with the exception that 85.5 parts of di-(beta-chloropropyl) ether are used invplace ofv 71.5 parts of di-(beta-chlo methyl) ether. Similarly bis - [beta-(4,6 - di amino pyrimidyl-Z thio) isopropyl] ether is pre Sodium hydroxide in mixture of 500 parts pared by using 85.5 parts of di-(beta-chloroiso_ water and 500 parts alcohol ________________ __ 40. 0 2 propyl) ether instead of 715 parts of di-(beta Di-(beta-chloroethyl) ether __________________ __ 71. 5 l 70 chloroethyl) ether as in Example 1. Example 7 The ?rst two components were mixed and a clear solution obtained. The di-(beta-chloro Beta,beta’-bis- (2,6-diaminopyrimidyl 1- 4 thio) 2-mercapto 4,6-diamino pyrimidine __________ __ 142. 0 2 ethyl) ether was now added and the resulting dipropyl ether and vbeta,beta'-:bis-(2,6-diamino mixture was heated under re?ux at the boiling 75 pyrimidyl-4 thio) di-isopropyl ether are prepared 8 7 Alpha; alpha'-bis-(4,6-diamino pyrimidyl-2 thio) in essentially the same manner as described un der Example 1 with the exception that 85.5 parts , of 'di-(beta-chloropropyl) ether or of- di-(beta diethyl thioether .' . ' ‘ Alpha,alpha'-bisr(4,6-diamino pyrimidyl-Z thio) diprOpyl ether ‘ l V : Alpha,alpha"-bis-(4,6-diamino pyrimidyl-2 thio) lpr'opyl butyl ether v ' :diethyl thioether chloroisopropyl) ether are used instead ofl71.5 parts of di- (beta-chloroethyl) ether and 142 parts of li-mercapto 2,6-diamino pyrimidine are used in place of 142 parts of 2-mercapto 4,6-‘diamino‘ pyrimidine. " Alpha, alpha'ebis- (2,6ediamino pyrimidyl-4 thio) ' ' ' V , v Alpha,beta'-(4,6'-di'amino pyrimidyl-Z thio) bu Illustrative examples of other compounds em_ ten-3'-yl butyl ether braced by Formula I that may be produced in 10 Beta,beta'-bis-[4,6 t-di - (?uoroanilino) pyrimid accordance with the present invention are listed y1-2 thioldiethyl etheruql. below: Beta,beta'-bis— [2,6-di- (methylamino) pyrimidyl 4 thio] diethyl ether ' ‘ pyrimidyI-Z Beta,beta’ -bis- [4,6-di-_(ethy1amino) thio] diethyl ether 7 V " ' ' ‘ether -: ' ' ' ' iAlpha,alpha'-bis-[4,(i- dit- (bromotoluido) pyri , midyl-2 thiol dipropyl ether Beta,beta’-bis-[4,6-di - (propenylamino) pyrimi dyl-2 thio] diethyl ether - Beta,beta'-bis-(4',6-diamino 5-chloromethyl py rimidyl-2 thio)» beta,beta’-dipheny1 diethyl ‘ ' ' Alpha,beta'-bis-(4,6-diamino 5-iodomethyl py ' rimidyl-2 thio) ‘diethyl ether Beta,beta'-bis- [4,6-di- (isobutylamino) pyrimidyl ‘ > Alpha,:beta' -bis-‘ (4-methylamino ‘ 6 - ‘chloroethyl 2 thio] diethyl ether amino pyrimidyl-2 thio) beta-phenyl alpha Beta,beta'-bis- (4,6-diani1ino pyrimidyl-2 thio) di ethyl ether ' Beta,-beta'-bis-(4,6-dianilino pyri-midyl-Z thio) diethyl thioether Beta,beta' -bis- [4,6-di- (methylamino) pyrimidyl ethyldibutyl thioether' rimidyle2 thio] diethyl ether c pyrimidyl-é‘thio] diethyl-thioether ‘ ‘ ' 30' ' diethyl thioether Beta,beta'-bis- [2,6-.di- (iodotoluido) E-iodophenyl pyrimidyl-4 thiol dipropyl ether v clohexyl pyrimidyl-2 thiol ‘diethyl ether ’ In a manner similar to that» described 'above Beta,beta'-bis- [4,6-di- (phenethylamino) pyrimi dyl-2 thio] diethyl ether ‘ ‘ » 35 Beta,beta'-bis-[4,6 - di - icyclohexylamino) 5-cy Beta,beta'-bis-(2,6-diamino 5-ethyl pyrimidyl-4 thio) diethyl thioether 5 — butyl pyrimidyl-2 thio] diethyl thioether Beta,beta’-bis-(4,6-diamino 5-methy1 pyrimidyl 2 thio) diethyl ether ‘ 5-chl0ro phenyl pyrimidy1-2 thio] diethyl ether Beta,beta'-bis-[4,6 - di v-(chloroanilin'o) Beta,beta'-bis'-(4,6-ditoluido pyrimidyl-2 thio) 5 - xenyl ‘ Beta,beta'-bis-[4,6 -‘ di - (octylamino) ‘ Beta,beta'-bis-(4,6-dixylidino pyrimidyl-2 thio) diethyl ether ' rimidyl-2 thio] dipropylthioether Beta,betaf -bis_ [2,6-di- (naphthylamino) Beta,beta'-bis-(4,6-ditoluido pyrimidyl-Q thio) 7 ' Beta,beta’t-bis-[4,6-di-(al1y1amino) 2 thio] diethyl thioether diethy1 ether . Beta, ' beta’-bis- [4,6-di-'(cyclohexenylamino) with particular reference to the preparation of " Beta;beta’ -bis- ] 4,6-di- (ethylanilino) pyrimidyl-Z V40 :bis-(LB-gdiazinyl thio), that is, bis-(pyrimidyl thio), dialkyl ethers ‘and thioethers, correspond thio] diethyl ether " - ing derivatives of 1the 1,2- or vortho-diazines (pyridazines) ‘and of the 1,4- or para-diazines Beta,beta’-bis-(4,6-diamino 5-pheny1 pyrimidyl-Z thio) diethyl ether (pyrazines) may be prepared. Beta,beta'-bis- [4,6-di-(methy1amino) 5-ethy1 py-. rimidy1-2 thio] diethyl ether Bis-(4,6-diamino pyrimidyl-Z thio) dimethyl ether “ ‘ 45 The method ' 'of_, preparing beta,beta'-bis- (4,6 _ Bisl-(2,6-diamino pyrimidyl-4 thio) diamino pyrimidy1-2 thio) diethyl ether which comprises addingdi-(beta-chloroethyl) ether to .a clear solution obtained ‘by mixing together ap proximately equal molar ratios of 2-mercapto dimethyl ether Bis- (4,6-diamino pyr'imidyl-Z thio) dimethyl thio ether - Bis-(2,6-diamino pyrimidyl-4 thio) ‘dimethyl “119- - ether Bis-(4,6-diamino 5-methy1 pyrimidyl-Z ‘thio). di-f _" methyl ether 4,6-diamino pyrimidine and sodium hydroxide dissolved in a mixture of ‘water and alcohol, the molar. amount of di-(beta-chloroethyl) ether P being approximately one-half- that of the molar amount of 2-mercapto 4,6-diamino pyrimidine, Bis-(2,6-diamino 5-phenyl pyrimidyl-é thio)‘ dri- : heating the resulting mixture under re?ux at the boiling temperature of the mass for a period of methyl thioether Bis-[4,6-di-(methy1amino) pyrimidy1-2 thiol di- ' methyl ether Bis-(4,6-dianilino pyrimidyl-Z thio) dimethyl ether ' ‘ ' Bis-(4-methylamin0 G-‘anilino pyrimidyl-Z dimethyl ether . ' ' ' ' - ' "thio) . r ' Alpha,beta'--bis-(4,6-diamino pyrimidyl-Z thio) methyl ethyl ether ’ 1 ' ' Alpha, alpha'-bi's-(4,6-diamino pyrimidyl-2 thio) ‘ Alpha, diethyl a1pha'-bisether (2,6-diamino , pyrimidyl-4 ., . thio)‘ __ diethyl ether _ What we claim asnew and desire to secure by Letters Patent of the United .States is: a the order of 7 hours, ?ltering off the precipitate CO comprising beta,beta'-bis-(4,6-diamino pyrim idyl-2 thio) diethyl ether that separates upon cooling the mass, washing the said precipitate with water to remove soluble salts, and drying the Washed material. GAETANO F. D’ALELIO. JAMES W. UNDERWOOD.