Neue Synthesen von Pyrazolo[1,5-a]-s-triazinen

Two new syntheses of pyrazolo[1,5-a]-s-triazines are reported: (a) Addition of acetyl isocyanate to 5-amino-3-methyl-pyrazole followed by hydrolysis yields N-(3-methyl-5-pyrazolyl)-urea ( 15 ), which on cyclisation with triethyl orthoacetate gives 2-hydroxy-4,7-dimethylpyrazolo[1, 5-a]-s-triazine ( 16 ). (b) Condensation of aminoguanidine with β-oxo-nitriles affords 1-amidino-5-aminopyrazoles 18 . These are cyclised to pyrazolo[1,5-a]-s-triazines 19--21 by reaction with orthoesters, acetic-formic anhydride, phenylisocyanide dichloride, dimethyl oxalate, N, N′-carbonyldiimidazole, and N, N′-thiocarbonyldiimidazole. The 4-amino group in 19 is converted by standard procedures to OH, SH, SCH₃, Cl and NRR′. Reaction of pyrazolo[1,5-a]-s-triazines 30 with electrophiles leads to compounds substituted at position 8, e.g. 32a--e .     

Synthesis of bridgeheaded nitrogen systems. s-triazolo[4,3-b]-as-triazine,s-triazolo[4,3-d]-as-triazine and s-triazolo[3,4-b]-1,3,4-Thiadiazole ring systems

By the reactions of hydrazino-as-triazines ( 1a-d and 5 ) with cyanogen bromide were synthesized s-triazolo-as-triazines ( 2a-d ) and ( 6 ). Likewise, similar reactions of amino-s-triazolethiols ( 7a-e ) gave s-triazolo-1,3,4-thiadiazoles ( 8a-e ). Compound 2a was brominated to 2g.     

Chemical and biological studies on dihydro-s-triazines. XVII. Modifications of the three-component synthesis favoring the formation of 2-guanidino-4-methylquinazoline byproducts

A modified three-component reaction of arylamines, cyanoguanidine, and acetone is described, wherein formation of anomalous guanidinoquinazoline byproducts is greatly enhanced at the expense of the normal dihydro-s-triazines. Four new guanidinoquinazolines and four new dihydro-s-triazines were synthesized via this modification, starting from 2,4-, 2,5-, 3,4-, and 3,5-dimethoxyaniline. The guanidinoquinazoline to dihydro-s-triazine ratio was much higher with 3,4- and 3,5-dimethoxyaniline than with 2,4-dimethoxyaniline. 2,5-Dimethoxyaniline gave an unexpectedly low yield of guanidinoquinazoline, apparently because of steric hindrance. The modified three-component synthesis was also examined in detail with 2-naphthylamine.     

s-Triazines. I. Linear,sulfur bridged-s-triazine oligomers

A number of new thioether and disulfide oligomers of s-triazine have been prepared and identified. The reactions between 2,4-diphenyl-s-triazine-6-thiol and chloro substituted-s-triazines are described. A suggested mechanism for the formation of 2,2′-thiobis-(4,6-diphenyl-s-triazine) from 2,4-diphenyl-s-triazine-6-thiol is discussed.     

Diazo-, azo-, and azidoazoles. VII. Imidazo[1,2-b]- versus imidazo[2,1-c]benzo-as-triazines

Treatment of 3-aminobenzo-as-triazines with bromoacetaldehyde ethylene acetal give linear tricyclic imidazobenzo-as-triazines, where 3-amino-7-methylbenzo-as-triazine 1-oxide yields the angular isomer. The structures of these compounds have been established by comparing their nmr spectra to those of pyrazolo [5,1-c]- and s-triazolo[5,1-c]benzo-as-triazines obtained form the appropriate azo derivatives by intramolecular cyclization.     

Diazo-, azo- and azidoazoles,and related compounds. 1. Synthesis of naphthoazolo-as-triazines from diazoazoles and 2-naphthol

Azo derivatives prepared by coupling 2-diazoimidazole, 3(5))diazopyrazole, 3(5)diazo-s-triazole, 4(5)diazo-v-triazole and diazotetrazole with β-naphthol have been cyclized to the corresponding naphthoazolo-as-triazines, an heterocyclic system related to azasteroids. The structure of the products have been elucidated. A consistent mechanism for the cyclization is proposed.     

Die Synthese von asymmetrisch substituierten o-Hydroxyphenyl-s-triazinen

Mono- and bis-(2-hydroxyphenyl)-s-triazines 4 , 14 , 18 , 22 , 28 , 29 can be prepared by (a) reaction of salicylic acid esters 2 with amidines 3 ; (b) reaction of 4H-1, 3-benzoxazin-4-ones 10 with amidines 3 ; and (c) Friedel-Crafts-reaction of chloro-s-triazines 26 , 27 with resorcinol 24 . In case (b) the path of reaction is determined by the character of substituent R⁴ in 10 . Scope and limitations of these reactions and accessibility of starting materials are discussed.     

Cyclisations par l'intermédiaire de fonctions phénylthioet phénoxy-carbamyle. I. Diphényl-1,2-alcoyl-5-dioxo-3,6-hexahydro-triazines-1,2,4

The N-(p-nitrophenoxy-carbonyl) and N-(phenylthio-carbonyl) derivatives of α-amino-acyl-hydrazides cyclize in presence of diazomethane, yielding hexahydro-1, 2, 4-triazines with simultaneous formation of p-nitro-anisole or thio-anisole respectively. The molecules with a phenoxycarbonyl function such as N-(phenoxycarbonyl)-glycyl-(N, N′-diphenylhydrazide) give the corresponding ring products and anisole only in solvents with high dielectric constant (e.g. nitromethane). The phenylthio-carbonyl derivatives give the same ring products in presence of lead acetate by the intervention of HO^?. The p-nitrophenoxycarbonyl derivatives give rise to the same cyclisations in the presence of pyridine by the intermediate of carbamyle-pyridinium ion acting as electrophile. These different types of intramolecular reactions are illustrated by the formation of 1, 2-diphenyl-5-alcoyl-3, 6-dioxo-1, 2, 4-hexahydro-triazines.     

Chemical and biological studies on dihydro-s-triazines. XVI. Nmr evidence for the formation of 2-guanidino-4-methylquinazolines as anomalous byproducts in the three-component synthesis

The three-component synthesis of 4,6-diamino-1-aryl-1,2-dihydro-2,2-dimethyl-s-triazines from arylamines. cyanoguanidine, and acetone has been studied by nmr spectral analysis in trifluoro-acetic acid solution. The presence of 2-guanidino-4-methylquinazoline contaminants can be discerned clearly at concentrations as low as 1%. Arylamines most likely to give significant proportions of guanidinoquinazoline byproducts are 2-naphthylamines and anilines containing one or more electron-donating meta-substituents.     

The mass spectra of s-triazines

The mass spectra of twenty-one s-triazines have been interpreted. An unusual feature noted in the spectra of some of the compounds is transfer of a hydrogen atom of a side chain to a nitrogen atom of the s-triazine ring; two such shifts are suggested as a rationale for the unusual loss of nitrogen from a hydrazide derivative. The fragmentation of triamino- and some diamino- derivatives indicates that imino tautomers play a significant role. The spectra of aryldiamino s-triazines suggest that the site of a substituent in the aryl ring is important in some cases in directing the decomposition; some transitions have been rationalised on the basis of the juxtaposition of the substituent in relation to a nitrogen atom of the heterocyclic ring.     

Untersuchung von 2.4.6-substituierten s-Triazinen durch Gaschromatographie-Massenspektrometrie

Gas chromatography mass spectrometry was used to examine a large number of 2,4,6-trialkoxy-s-triazines. The fragmentation of these compounds upon electron impact is discussed. This method permits reliable and rapid identification of mixtures of triazines obtained by reaction of 2,4,6-trichloro-s-triazine with mixtures of alcohols.     

Heterocyclen, 48. Mitt.: Synthesen von substituierten 1,3,5-Triazinen und über eine neuartige Synthese substituierters-Triazolo[4,3-a] 1,3,5-triazine

Zusammenfassung Durch stufenweisen Austausch von Chloratomen im 2,4,6-Trichlor-1,3,5-triazin wurden verschiedene unsymmetrisch substituierte Derivate des 1,3,5-Triazins synthetisiert. Von einigen Hydrazinotriazinen ausgehend gelang die Synthese von substituiertens-Triazolo[4,3-a]-1,3,5-triazinen.

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By a successive replacement of the chlorine atoms in 2.4.6-trichloro-1.3.5-triazine it was possible to synthesize different unsymmetrically substituted derivatives of 1.3.5-triazine. Some hydrazino triazines were used as starting material for the synthesis of substituteds-triazolo[4.3-a]-1.3.5-triazines.

     

1-Aryl-4,6-diamino-1,2-dihydro-s-triazines. Contrasting effects on intestinal helminths,bacteria, and dihydrofolic reductase

The preparation of a variety of novel 1-aryl-4,6-diamino-1,2-dihydro-s-triazines is described. These compounds exhibit an array of contrasting effects on intestinal helminths, bacteria, and dihydrofolic reductase. It is concluded that potent anthelmintic activity among the dihydro-triazines is not dependent solely on the bulky-substituent hypothesis advanced by other investigators, and indeed cannot reliably be predicted on this basis.     

TiCl4 Induced N-Methyleneamine Equivalents. 21. First Synthesis of Anilinomethylazides

TiCl₄ induced N-methyleneamine equivalents from N-(methoxymethyl)anilines or 1,3,5-triphenylhexahydro-1,3,5-triazines were reacted with trimethylsilylazide to give anilinomethylazides.     

Synthesis and Properties of sym-Triazine Derivatives. 18. Synthesis of N-Substituted 2,4-Diamino-6-(benzothiazolyl-2-thiomethyl)-sym-triazines

The condensation of methyl benzothiazolyl-2-thioacetate with N-substituted biguanides in the presence of sodium methylate gave 2-amino-4-(RR'-amino)-6-(benzothiazolyl-2-thiomethyl)-sym-triazines. In a number of cases the 1,1-disubstituted 5-(benzothiazolyl-2-thioacetyl)biguanides could also be separated and these could be cyclized by refluxing in DMF to the corresponding substituted sym-triazines described. The latter type of compound was also synthesized by treating 2-amino-4-trichloromethyl-6-(benzothiazolyl-2-thiomethyl)-sym-triazine with primary and secondary aliphatic and heterocyclic amines or by the reaction of N-substituted 2,4-diamino-6-chloromethyl-sym-triazines with 2-mercaptobenzothiazole.     

Ene syntheses in the s-triazine series

β-Oxo-s-triazines undergo an ene synthesis with dienophiles. The ease of the reaction depends on the substituents of the triazine ring and on the nature of the enophile.     

Synthesis and properties of some aryl-s-triazines

The synthesis and reactions of several substituted s-triazines were studied in attempts to prepare 4,6-bis(4-chlorophenyl)-s-lriazine-2-carboxylie acid ( 2 ) and 2-aldehyde ( 8 ). The 4,6-bis-(4-chlorophenyl)-s-triazine derivatives were surprisingly inert to a variety of reagents. 4,6-Bis-(4-chlorophenyl)-2-methyl-s-triazine ( 1 ) could not be oxidized with any of a variety of oxidants. On bromination 1 gave 4,6-bis(4-chlorophenyl)-2-dibromomethyl-s-triazine ( 4 ) which was resistant to hydrolysis but on oxidation with selenium dioxide gave 2 . Compound 2 was also prepared by the oxidation of 4,6-bis(4-chlorophenyl)-2-hydroxymethyl-s-triazme ( 7 ) with potassium permanganate. Other reagents did not oxidize 7 to 8 . 4,6-Bis(4-chloroanilino)-2-mcthyl-s-triazine ( 3 ) was also resistant to oxidizing agents. 2-Diazomethy1-4,6-dichloro-s-triazine ( 11 ) on reaction with 4-chloroaniline gave 4,6-bis(4-chloroanilino)-2-chloromethyl-s-triazine ( 12 ). All efforts to prepare 8 were unsuccessful.     

Derivatives Of ditraizinylamine and tritriazinylamine

2-Arylamino-4,6-dichloro-s-triazine reacts with cyanuric chloride in the presence of alkali to yield N,N-bis(4,6-dichloro-s-triazin-2-yl)-arylamine. In like manner, 2-substituted o-chloro-, p-chloro-, o-nitro- and p-carbomethoxyphenylamino-4,6-dimethoxy-s-triazines react with cyanuric chloride to yield the corresponding 4,6-dichloro-s-triazin-2-yl-4′,6′-dimethoxy-s-triazin-2′-ylaryl-amine, while anilino-, p-toluidino, o- and p-methoxyphenylamino and o-carbomethoxyphenylamino derivatives did not. The reaction of cyanuric chloride with 2,4-dichloro-6-ethylamino-s-triazine in the presence of alkali yields the condensation product of the ditriazinylamine type and the reaction of cyanuric chloride with ammonia yields N,N-bis(4,6-dichloro-s-triazin-2-yl)- or tris(4,6-dichloro-s-triazin-2-yl)amine.     

The syntheses and thermal rearrangement of some methiodides of s-triazolo[4,3-a]pyridines

It has been shown that the N-methylation, with methyl iodide, of s-triazolo[4,3-a]pyridines affords a mixture of the N-1 and the N-2 methiodides. The N-2 methiodides can be thermally rearranged to the N-1 methiodides. The 8-methyl N-1 methiodides exhibit peri interaction between the two methyl groups. This interaction is reflected in greater stability of the N-2 methiodide vs. the N-1 compound.     

A new synthesis of s-triazines

The unions of urea, guanidine, thiourea, biguanide, and biuret were reacted with aromatic nitriles to yield s-triazines. Ortho-chloro substituted aromatic nitriles gave other products or did not react because of steric factors.