Unusual reaction of cyanoacetic acid esters with sym-triazine monoazides

Abstract

Continuing our studies on synthesis of derivatives in the sym-triazine series based on 2-azido-4,6-disubstituted 1,35-triazines [1-3] by reactions of compounds 1a-d with methyl cyanoacetate and ethyl cyanoacetate, we obtained derivatives of a novel coupled heterocyclic system: 2-[1,3,5]triazin-2-yl-1,2-dihydro[1,2,3,4]tetrazine-5-carboxylic acid esters 2a-d. a R 1 = NH 2 , R 2 = NEt 2 ; b R 1 = R 2 = NMe 2 ; c R 1 = PhNMe, R 2 = NMe 2 ; d R 1 = NH 2 , R 2 = piperidino; a, b R 3 = Me, c, d R 3 = EtThe IR spectra were recorded in nujol mulls of the samples on a Specord IR-75 spectrometer. The 1 H NMR spectra were recorded on a Bruker DRX-500 spectrometer (500 MHz) in DMSO-d 6 , internal standard TMS. The mass spectra were taken on a Finnigan MAT INCOS50 (ionizing radiation energy, 70 eV). TLC was run on Silufol UV-250 plates in the system 1:1 acetone-hexane.(4-Amino-6-diethylamino[1,3,5]triazin-2-yl)-1,2-dihydro[1,2,3,4]tetrazine-5-carboxylic Acid 2-Methyl Ester (2a). A solution of Na (0.16 g, 7.2 mmol) in methanol (5 ml) was added in small portions at room temperature with stirring to a solution containing 2-amino-4-(diethylamino)-6-azido-1,3,5-triazine (1 g, 4.8 mmol) and methyl cyanoacetate (0.48 g, 4.8 mmol) in absolute methanol (10 ml). Then the reaction mixture was stirred for another 30 min at the same temperature, and then it was boiled for 1 h and cooled down. The solvent was evaporated down to 2/3 volume, and then it was diluted with ice water (50 ml). Then it was acidified with 50% acetic acid to pH 7; the precipitate formed was separated, washed until the wash water tested neutral, and dried in air. The product was recrystallized from alcohol. Yield 1.25 g (85%); mp, 223-224°C. __________________________________________________________________________________________

Synthesis and structure of new 1,2,3-triazolyl substituted 1,3,5-triazines

“…Compounds 3d, 3g, 4b, and 5a-c displayed the maximum intensity of the molecular ions. The fragmentation patterns of the molecular ions under electron impact were found to be the same as it was observed for the earlier synthesized heterocyclic derivatives of the 1,3,5-triazine [8,11,25].…”

“…Previously, we reported that using esters of cyanoacetic acid as a methylene active reagent in reaction with 2-azide-4,6-disubstituted-1,3,5-triazines lead to the formation of sixmembered 1,2,3-triazinyl-1,2,3,4-tetrazines [11]. It was interesting to compare different reaction conditions for the similar reaction of azido-derivatives of 1,3,5-triazine with less reactive cyanoacetamide (CAA) as a reagent.…”

“…It was interesting to notice, that using cyanoacetic acid esters as starting compounds in a similar reaction unexpectedly lead to the formation of a new connected heterocyclic system containing two six membered heterocycles-1,2,3,4-tetrazine and 1,3,5-triazine [11]. An even more exoticly connected heterocyclic aromatic system containing 1,3,5-triazine and 1,2,4-oxadiazol cycles has been synthesized by our group and reported recently [12].…”

Synthesis of new 4,6-disubstituted-1,3-5-triazin-2-yloxy esters and N-hydroxyamides

“…Compounds IIIc and IVc have the maximum intensity of the molecular ions. The fragmentation pattern of the molecular ions under electronic impact is the same as has been observed for the synthesized heterocyclic derivatives of the 1,3,5-triazine [36,37,[40][41][42][43].…”

“…Furthermore, 1,3,5-triazine derivatives posses a wide variety of biological activity as HIV treatment, and as catalysts, herbicides, carcenolytics [17][18][19][20], as well as compounds with growth-stimulating activity, antidote activity, nontoxic cationic surfactants, and inhibitors of the oil oxidizing processes [21][22][23][24][25][26][27][28].…”