A novel straightforward synthesis of 2,4,6-triaryl-1,3,5-triazines via copper-catalyzed cyclization of N-benzylbenzamidines

A novel, straightforward method for the synthesis of 2,4,6-triaryl-1,3,5-triazines via copper-catalyzed cyclization of N-benzylbenzamidines in DMSO has been developed. Compared to other methods, the present protocol has a number of advantages such as—cost-effectiveness, avoidance of aldehydes or alcohols as reaction partners, and easy accessibility of starting materials, making it a highly practical approach to access various 2,4,6-triaryl-1,3,5-triazines.     

A general approach toward the synthesis of 8-acylamidopyrazolo[1,5-a]-1,3,5-triazines

An expedient synthesis of 8-acylamidopyrazolo[1,5-a]-1,3,5-triazines was developed by treating 8-amino-4-[N-(4-aminophenyl)-N-(methyl)amino]pyrazolo[1,5-a]-1,3,5-triazine with various acyl chlorides following by the displacement of the so-formed N-(methyl)-N-[4-(acylamido)phenyl]amino leaving group with various amines. Applications to high-throughput synthesis are suggested.     

Reaction of N-cyanoformimidates with some heterocyclic compounds. A new synthesis of 5-azaadenine and related compounds

3-Amino-1,2,4-triazoles and 2-aminobenzimidazole were reacted with N-cyanoimidates to give 5-amino-1,2,4-triazolo[2,3-a]-1,3,5-triazines (5-azaadenines) and 4-aminobenzimidazo[1,2-a]-1,3,5-triazines, respectively. The structures of the compounds obtained were confirmed through the comparison with some of the possible isomers prepared by independant methods.     

The umpolung of substituent effect in nucleophilic aromatic substitution. A new approach to the synthesis of N,N-disubstituted melamines (triazine triskelions) under mild reaction conditions

By the umpolung of substituent effect 1,3,5-triazines substituted with three dialkylamino groups were prepared under mild reaction conditions by treatment of cyanuric chloride with tertiary amines. Quaternary N-triazinylammonium salts were identified as reactive intermediates activating the triazine ring and strongly promoting the persubstitution of all chlorine atoms. The final degradation of intermediate N-triazinylammonium chlorides proceeded at room temperature or in boiling dichloromethane spontaneously within irreversible evolution of appropriate chloroalkane.     

Reaction of Potassium Salts of N-(Thio)phosphorylthioamides with Chlorinated 1,3,5-Triazines

Potassium salts of N-(thio)phosphorylthioamides can substitute one, two, or three halogen atoms in chlorinated 1,3,5-triazine molecules to give the products of imidothiyl structure. At low temperature, products of incomplete substitution of halogen in the starting 1,3,5-triazines can be obtained.     

Synthesis of 4H-1,3-benzoxazin-4-ones from 2,2-diazidobenzofuran-3(2H)-ones

Benzoxazine derivatives are useful building blocks and display various biological activities. We serendipitously discovered and subsequently developed a new one pot method for the synthesis of 2-(dimethyl amino)/2-morpholino/2- (piperidin-1-yl)-4H-benzo[e][1,3]oxazin-4-ones from corresponding substituted 2,2-diazidobenzofuran 3(2H) - ones and N-formyl dimethyl amine (DMF)/N-formylmorpholine/N-formylpiperidine using m-CPBA at 100?°C in moderate to good yields. We also demonstrated the utility of 4H-benzoxazines for the synthesis of other medicinally important compounds such as 2-hydroxyphenyl substituted 1,2,4-triazoles, unsymmetrical 1,3,5-triazines, and 1,2,4-oxadiazoles.     

New synthesis of 2,4-dialkyl(or diaryl)pyrazolo[1,5-a]-1,3,5-triazines

Reactions of monothiodiacylamines or N-aroylthioimidates with 3-aminopyrazoles gave pyrazolo[1,5-a]-1,3,5-triazines in good yields.     

The Oxidation of Hexahydrotriazines

Summary. N-Alkyl-2,4-dioxohexahydro-1,3,5-triazines oxidize readily with oxygen to the corresponding cyanuric acid derivates. The oxidation of 1,3,5-trimethyl-2,4-dioxohexahydro-1,3,5-triazine resulted in a stable form of hydroperoxide. During the oxidation of 1,3,5-trimethyl- 6-phenyl-2,4-dioxohexahydro-1,3,5-triazine this hydroperoxide could not be identified, however, the result was the stable reaction product bis-[6-phenyl-1,3,5-trimethyl-2,4-dioxohexahydro-1,3,5-triazin]peroxide.     

Heterocycles from heterocycles. - III[1]. 1,3,5-trisubstituted hexahydro-1,3,5-triazines-2-ones from 1,3,5-trisubstituted hexahydro-1,3,5-triazines and organic isocyanates

1,3,5-Triscubstituted hexahydro-1,3,5-trazin-2-ones 3 are easily obtained by the reaction of 1,3,5-trisub-stituted hexahydro-1,3,5-triazines 1 with organic isocyanates 2 . The reaction is believed to occur by the sequential addition to 2 of two molecules of the monomeric N-methyleneamines in thermal equilibrium with 1. Substituent scrambling at the operating temperature (120°) was negligible. The crystal structure of 1,3,5-triphenylhexahydro-1,3,5-triazin-2-one (3a) has been determined by X-ray diffraction methods.     

Synthesis of unsymmetrical 2,4-dialkylpyrazolo[1,5-a]-1,3,5-triazines

The reaction of 3-aminopyrazole with imidate esters such as ethyl acetimidate, gave N-(pyrazol-3-yl)acetamidine (1) rather than the isomeric 2-acetamidoyl-3-aminopyrazole. Ring closure of 1 with orthoesters such as ethyl propionimidate, afforded unsymmetrically substituted 2.4-dialkylpyrazolo[1,5-a]-1,3,5-triazines such as 4-ethyl-2-methylpyrazolo[1,5-a]-1,3,5-triazine (3). The structure of 1 was confirmed by several alternate syntheses. The unique feature of this two-step synthetic approach to the synthesis of pyrazolo[1,5-a]-1,3,5-triazines is that it is a convenient method of preparing fused triazines based on available pyrazoles rather than the less accessible dialkyltriazines.     

Synthesis of 4-amino-6-chloro-1,3,5-triazin-2(1H)-ones

Conditions for selective substitution for one chlorine atom in 2-(R,R??-amino)-4,6-dichloro-1,3,5-triazines with a hydroxide ion were elaborated. Spectral and calculation methods showed that the products formed are in the lactam form, i.e., have the structure of 4-chloro-6-(R,R??-amino)-1,3,5-triazin-2(1H)-ones.     

Synthesis and structure of new 1,3,5-triazine-pyrazole derivatives

We have studied the reaction of methylenedicarbonyl compounds with 4,6-disubstituted 2-hydrazinyl-1,3,5-triazine in order to obtain novel coupled biheterocyclic aromatic systems with potential bioactivity. Reaction conditions were studied and optimized, and a series of 4,6-disubstituted 2-(1H-pyrazolyl)-1,3,5-triazines were obtained with good yield.     

Heterocycles from N-benzoylthioamides and dinucleophilic reagents

N-Benzoylthioamides ( 1 ) react with hydrazines and hydroxylamine to form 1H-1,2,4-triazoles and 1,2,4-oxadiazoles, respectively. A similar treatment of the S-methyl derivatives of 1 with amidines leads to 1,3,5-triazines. Ethyl ZV-benzoylthiocarbamate undergoes analogous reactions to yield the corresponding ethoxyheterocycles.     

Heterocyclen, 73. Mitt.: Synthesen einiger substituierter 1,3,5-Triazine und Imidazo[1,2-a]-[1,3,5]-triazine

Zusammenfassung Substituierte 1,3,5-Triazine mit verschiedenen funktionellen Gruppen wurden synthetisiert und einige Azido-1,3,5-triazine wurden aufeine denkbare Azido—Tetrazol-Valenz-Isomerisierung untersucht; nur die Azid-Form konnte jedoch nachgewiesen werden. Von einigen Amino-1,3,5-triazinen ausgehend, gelang die Synthese von substituierten Imidazo[1,2-a]-[1,3,5]-triazinen.

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Heterocycles, LXXIII: Synthesis of some substituted 1.3.5-triazines and imidazo[1,2-a]-[1.3.5]-triazines

The synthesis of 1.3.5-triazines carrying various functional groups is described. 1.3.5-triazines with azido groups were studied for possible azido-tetrazolo valence isomerization; however, only the azido form could be detected. Some amino-1.3.5-triazines were used as starting material for the synthesis of substituted imidazo[1,2-a]-[1.3.5]-triazines. *** DIRECT SUPPORT *** A3615139 00009

     

Synthesis of 1-(N-arylaminomethyl)-3-methyl-1,8-dihydrocycloheptapyrazol-8-ones

Reactions of 3-methyl-1,8-dihydrocycloheptapyrazol-8-one ( 2 ) with arylamines in the presence of formaldehyde gave 1-(N-arylaminomethyl)-3-methyl-1,8-dihydrocycloheptapyrazol-8-ones 5a-l in good yields. 1,3,5-Tris(phenyl- and 4-methoxyphenyl)hexahydro-1,3,5-triazines or bis(3-nitroanilino)methane, which were condensation products of arylamines and formaldehyde, also reacted with compound 2 to afford 5a,c,j , respectively.     

Organocatalytic asymmetric [3+2]-cycloaddition of 3-isothiocyanato oxindoles with 1,3,5-trisubstituted-hexahydro-1,3,5-triazines to access spiro-imidazolidinethione-oxindoles

An efficient asymmetric [3 + 2]-cycloaddition reaction of 3-isothiocyanato oxindoles and formaldimines in-situ generated from 1,3,5-trisubstituted-hexahydro-1,3,5-triazines with a cinchona alkaloid-derived thiourea as the catalyst has been developed. A range of biologically important spiro-imidazolidinethione-oxindoles were obtained in excellent yields with good enantioselectivities (up to 99% yield and 93% ee).     

Introduction of a triflate group into sterically-hindered positions in 1-aryl-4,6-diamino-1,3,5-triazines and their dimroth rearrangement products

Decomposition of 1-(azidophenyl)-4,6-diamino-1,3,5-triazines 11–13 and their 4-amino-6-(azidoanilino)-1,3,5-triazine isomers 31–33 in trifluoromethanesulphonic acid at 0° led to the introduction of the triflate group (OSO₂CF₃) into the aryl group. This method can be employed to introduce a bulky substituent into the hindered position ortho to the triazinyl substituent. Dimroth rearrangement of 1-(aryl)-4,6-diamino-1,3,5-triazines is best effected in refluxing ethanolic pyridine.     

The synthesis of 7,8-dihydroimidazo[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines, 8,9-dihydro-7H-pyrimido[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines and 7,8,9,10-tetrahydro[1,3]diazepino[1,2-e]pyrazolo[1,5-a]triazines

Cyclic hydrazino amidines were converted to the corresponding aminopyrazolyl derivatives. Ring closure between the amino groups of pyrazoline moieties and NH groups of cyclic amidines afforded the following ring systems: 7,8-Dihydroimidazo[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines, 8,9-dihydro-7H-pyrimido[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines and 7,8,9,10-tetrahydro[1,3]diazepino[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines.     

One- electron transfer properties and herbicidal activity of diquaternary salts of 2,4-di-(4-pyridyl)-1,3,5-triazines

Diquaternary salts of 2,4-di-(4-pyridyl)-1,3,5-triazines have been prepared. The salts can be regarded as reversible one electron transfer systems with redox potentials (E₀) of about ?0·44 V in the pH range 7·0–8·5. 2,4-Bis-(4-methyl-4-pyridinio)-1,3,5-triazinediium dihalides are effective post-emergent herbicides at application rates of 4–6 kg/hectare.