Synthesis of Novel Architectures from Triazinyl Hydrazines and Various Carbonyl Compounds

Sharma, Vishal

Publication

Synthesis of Novel Architectures from Triazinyl Hydrazines and Various Carbonyl Compounds

Sharma, Vishal

Date

2020

Abstract

The pH labile nature of hydrazones has made them useful in various fields from material to medical science. Here, explorations of triazinyl hydrazones are reported. Three different projects will be described; the hydrolysis of novel triazinyl hydrazones, the synthesis of remarkably stable hemiaminals, and the creation of macrocycles derived from hydrazone dimers. Novel triazinyl hydrazones. Elaborating on previous work, the role of N -alkylation on hydrazone hydrolysis was studied using ArNHNH 2 , ArN(CH 3 )NH 2 and ArN(Ph)NH 2 wherein Ar is a triazine ring. The study relied on four different carbonyl donors. The use of diketones affords an opportunity to study the effects of intramolecular hydrogen bonding when N -alkylhydrazines (which preclude pyrazole formation) are employed. Hydrolysis rates were measured by high performance liquid chromatography (HPLC) using an established competitive exchange reaction relying the presence of an excess of formaldehyde. The studies show that the presence of methyl group increases hydrolysis rates when compared to phenyl (which is similar) and to unalkylated hydrazones which proceed most slowly. Stable hemiaminals. During the synthesis of hydrazones, stable cyclic hemiaminals were observed. Cyclic hemiaminals are obtained from acidic conditions using an aromatic ring containing hydrogen bond acceptor and diketones with strong electron withdrawing groups. Triazine ring provides three hydrogen bond acceptors and, hence, used to create stable cyclic hemiaminals under acidic conditions. By surveying a range of 1,3-diketones, stability is attributed to the effect of hydrogen bonding and the presence of a strong electron withdrawing group (trifluoromethyl). Using resistance to dehydration as a surrogate for stability, these hemiaminals survives in ambient, neat glacial acetic acid for long periods of time and requiring reflux for conversion to the corresponding pyrazole. DFT calculations corroborate design criteria that are crucial for the stability. Macrocycles. Finally, an earlier report from the Simanek group identified three macrocycles that derive from dimerization of a protected triazinyl hydrazine bearing an acetal when exposed to acid.8 The resulting bishydrazone presented 24 atoms in a ring. The simplicity of monomer preparation and the nearly quantitative yields of product led to the question of whether rings of varying sizes could be prepared. Ring size is readily manipulated by changing the tether between the acetal and triazine ring which contains an amino acid and an amino acetal. For these studies, 6 monomers were prepared using glycine and ?-alanine along with acetals including the 2-carbon aminoethyl acetal, the 3-carbon aminopropyl acetal, and the 4-carbon aminobutyl acetal. Treatment with trifluoroacetic acid and slow evaporation of solvent yielded macrocycles that are characterized by x-ray diffraction, 1 H and 13 C NMR spectroscopy, mass spectrometry and HPLC. Macrocyclic homodimers of ring sizes of 22-28 atoms were obtained in high yield. In addition, when a 1:1 mole ratio of different monomers were mixed, heterodimeric macrocycles with odd-numbered ring sizes (23-27 atoms) were also made. Solid state structures and solution state NMR studies suggest that these macrocycles form networks of hydrogen bonds and might be templated by protonation.