2-Amino-1,3,5-triazine chemistry: hydrogen-bond networks, Takemoto thiourea catalyst analogs, and olfactory mapping of a sweet-smelling triazine

Abstract

The chemistry of 4,6-dialkyl-2-amino-1,3,5-triazines with bulky alkyl substituents was investigated and their use as building blocks for preparing chiral thiourea organocatalysts explored. Reaction of ammonia with 4,6-di-tert-butyl-2-chloro-1,3,5-triazine gave 4,6-di-tert-butyl-1,3,5-triazin-2-amine which formed extended hydrogenbond networks in the solid state according to X-ray crystallography. Selected heterocyclic amines were converted to isothiocyanates, and the latter reacted with (S,S)-2-(dimethylamino)cyclohexylamine to give enantiopure 1-hetaryl-3-[2-(dimethylamino)cyclohexyl]thioureas, with hetaryl representing either 4,6-dimethyl-1,3-diazin-2-yl, 4,6-diisopropyl-1,3,5-triazin-2-yl, or 4,6-di-tert-butyl-1,3, 5-triazin-2-yl groups. These compounds are structural analogs of Takemotos's chiral thiourea organocatalysts (1-[3,5-bis(trifluoromethyl)phenyl]-3-[(1S,2S)-2-(dimethylamino)cyclohexyl]thiourea) with an aza-aryl instead of the 3,5-bis(trifluoromethyl)phenyl group. They feature a strong intramolecular N-H to N-1 hydrogen bond, as shown by X-ray crystallography of 1-(4,6-di-tert-butyl-1,3,5-triazin-2-yl)-3-[2-(dimethylamino)cyclohexyl]thiourea in the solid state and by 1 H NMR spectroscopy of all derivatives in CDCl 3 solution, which prevents them from acting as bifunctional organocatalyst. In the reaction of 4,6-di-tertbutyl-2-chloro-1,3,5-triazine with ammonia, 4,6-di-tertbutyl-2-ethoxy-1,3,5-triazine was identified as side-product displaying a mildly sweet, floral odor that is unusual for a 1,3,5-triazine. Analogs ([35) of 4,6-di-tert-butyl-2-ethoxy-1,3,5-triazine were prepared to define the important structural factors of the olfactophore. Graphical abstract N N N H N tBu tBu N S H Me 2 N N N N NH 2 tBu tBu

Ultrafast Excited-State Dynamics of Cytosine Aza-Derivative and Analogues

“…The same measurements were also carried out on 2-AT at neutral pH in buffer solution and the corresponding TA spectra are illustrated in Figure e−f while the dynamics are shown in Figure c for comparison. Previous study reported the p K a value of 2-AT should be 2.9 and 14.9, suggesting that 2-AT is in neutral form in buffer solution (pH = 7.4) and the interference from tautomer should not exist in our study. Again, the TA signals build up within the instrument resolution just like 5-AC and 2,4-DT.…”

Base-Mediated Synthesis of Unsymmetrical 1,3,5-Triazin-2-amines via Three-Component Reaction of Imidates, Guanidines, and Amides or Aldehydes

“…Because 1,3,5-triazin-2-amines exhibit various biological and medicinal activities, various methods for the synthesis of diverse 1,3,5-triazin-2-amines have been developed . However, the direct synthesis of 1,3,5-triazin-2-amines from readily available substrates is rare.…”