Crystal structure and antidiabetic activity of 2-aminospiropyrazolinium tosylates and the product of O-tosylation of β-(benzimidazol-1-yl)propioamidoxime

Abstract

2-Amino-1,5-diazaspiro[4.5]dec-1-en-5-ium salts possess bioactivity tuned by the nature of the heteroatoms in the six-membered ring and the counter-ion. The molecular environment of these cations in solids provides an opportunity to establish the conformations and hydrogen-bonding patterns typical for this family. β-Aminopropioamidoxime tosylation products [2-amino-1,5-diazaspiro[4.5]dec-1-en-5-ium tosylates and the product of the O-tosylation of β-(benzimidazol-1-yl)propioamidoxime, namely, 2-amino-1,5-diazaspiro[4.5]dec-1-en-5-ium tosylate, C8H16N3 +·C7H7O3S− (6), 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium tosylate, C7H14N3O+·C7H7O3S− (7), the monohydrate of 7, C7H14N3O+·C7H7O3S−·H2O (7a), 2-amino-8-thia-1,5-diazaspiro[4.5]dec-1-en-5-ium tosylate, C7H14N3S+·C7H7O3S− (8), 2-amino-8-phenyl-1,5,8-triazaspiro[4.5]dec-1-en-5-ium tosylate, C13H19N4 +·C7H7O3S− (9), and 3-(1H-benzimidazol-1-yl)-N′-(tosyloxy)propanimidamide, C17H18N4O3S (10)] were investigated using X-ray diffraction to study peculiarities of their molecular geometry and intermolecular interactions. In vitro antitubercular and antidiabetic screening of the β-aminopropioamidoxime tosylation products was also carried out. It was revealed that this series of compounds does not have activity against drug-sensitive and multidrug-resistant M. tuberculosis strains, and exhibits high and moderate antidiabetic α-amylase and α-glucosidase activity. Using the hydrogen-bond propensity tool, we found that the inclination of counter-ions and atoms to act as acceptors of hydrogen bonds for the amino group decreases passing from tosylate O atoms to water molecules and the N atoms of five-membered rings. This fact is probably the reason for the formation in the solids of hydrogen-bonded tetramers consisting of two anions and two cations, and the rare occurrence of 2-aminospiropyrazolinium salt hydrates.

N-N(+) Bond-Forming Intramolecular Cyclization of O-Tosyloxy β-Aminopropioamidoximes and Ion Exchange Reaction for the Synthesis of 2-Aminospiropyrazolilammonium Chlorides and Hexafluorophosphates

“…The synthesis of 2-aminospiropyrazolilammonium chlorides 9-12 at the first stage included tosylation of four β-aminopropioamidoximes, where the β-amino group contains piperidin-1-yl (1), morpholin-1-yl (2), thiomorpholin-1-yl (3), or 4 -phenylpiperizin-1-yl (4) in CHCl 3 at r.t. in the presence of diisopropylethylamine for 15-20 h with TLC monitoring. A series of toluenesulfochlorides (5-8) has been described by our team previously [35,36]. The tosylation products isolated as white precipitates were recrystallized from i-PrOH in 45-65% yields.…”

“…by our team previously [35,36]. The tosylation products isolated as white precipitates were recrystallized from i-PrOH in 45-65% yields.…”

“…The reaction of exchange of tosylate anion for chloride anion proceeds instantaneously-after dropping an ether solution of HCl to the tosylates 5-8 ethanol solution, white flakes of chlorides 9-12 are immediately formed, and after recrystallization from i-PrOH, their yields were 55-97% (Scheme 3, Table 1). by our team previously [35,36]. The tosylation products isolated as white precipitates were recrystallized from i-PrOH in 45-65% yields.…”