Title:Novel Synthesis of N-(1,3-Dioxoisoindol-2-yl)aminothiocarbohydrazide, and its Arylidenes and Glycosylidines as Precursors for Hybrids with Thiadiazoline Ring. Equilibration of the Glycosylidine Open Chain with the Cyclic Structures and Conformation of the Acyclic Analogues
Volume: 15
Issue: 7
Author(s): El Sayed H. El Ashry*, Laila F. Awad, Mahmoud Nasr, Ahmed A. Kassem and Mohamed A. Zakaria
Affiliation:
- Department of Chemistry, Faculty of Science, Alexandria University, Alexandria,Egypt
Keywords:
Thiosemicarbazides, N-(1, 3-dioxoisoindol-2-yl)aminothiocarbohydrazide, thiadiazoline, acyclo C-nucleoside, conformation,
hybrid heterocycles.
Abstract: Aim and Objective: Reaction of phthalic anhydride (1) with thiocarbohydrazide (2) in methanol
gave the intermediate (6) whose boiling in water or ethanol gave N-(1,3-dioxoisoindol-2-yl)aminothiocarbohydrazide
(5); where its Condensation with aldehydes and aldoses 9a-d afforded the respective thiosemicarbazide
derivatives. The manno-derivative 10, the D-galacto derivative 11 and the L-arabino derivative 12
exist in the cyclic pyranosyl structures undergo equilibration, in solution of DMSO, with their acyclic structures.
Dehydrative cyclization to the thiadiazoline derivatives and the acyclo C-nucleoside was done by refluxing
in acetic anhydride.
Materials and Methods: Commercially available solvents and reagents were purified according to the standard
procedures. Thin layer chromatography (TLC) was performed on plastic plates Silica Gel 60 F254 (E-Merk,
layer thickness 0.2 mm) with detection by UV light absorption. IR spectra were recorded for the compounds in
a KBr matrix with a Unicam SP 1025 spectrophotometer. NMR spectra were measured with Jeol spectrometer
(500 MHz). Chemical shifts (δ) are given in ppm relative to the signal for TMS as internal standard, and coupling
constants in Hz. The 13C NMR spectra were recorded with JEOL spectrometer at 125.7 MHz. The assignments
of 1H NMR spectra were based on chemical-shift correlation DQFCOSY spectra, while the assignment
of 13C NMR spectra were based on heteronuclear multiple quantum coherence, HMQC experiments.
Results: The N-(1,3-dioxoisoindol-2-yl)aminothiocarbohydrazide (5) was prepared, which incorborated the
1,3-dioxoisoindole ring that linked to thiosemicarbazide moiety. Such feature found to be excellent precursor
for the synthesis of hybrid of bi-heterocycles, the dioxoisoindolyl and thiadiazoline rings which could of potential
biological activity. The reaction of thiocarbohydrazide with phthalic anhydride in a detailed manner and
investigate its further reaction with aromatic aldehydes and sugars, then converting them to the target biheterocycles
and nucleosides was studied. The conformations of the acyclic alditolyl residues or the acyclic Cnucleosides
have been explained.
Conclusion: The new functionalized isoindolyl ring with thiosemicarbazide as in N-(1,3-dioxoisoindol-2-
yl)aminothiocarbohydrazide (5) resulted from the reaction of phthalic anhydride with thiocarbohydrazide via
the intermediate open chain derivative 6. It is a valuable precursor for the synthesis of thiosemicarbazones containing
sugar moieties 10-13. Their solutions in DMSO-d6 showed that the products exist in one form after
immediate dissolution that equilibrated with time to show a mixture of acyclic and cyclic forms. They have
been exploited as scaffolds for generation of potential hybrids of thiadiazoline derivatives containing isoindolyl
rings as well as their acyclo C-nucleosides 10a-13a and 14-15. The conformations of the acyclic alditolyl
residues or the acyclic C-nucleosides have been deduced from their spectral analysis.
