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

El Sayed H. El Ashry, Laila F. Awad, Mahmoud Nasr, Ahmed A. Kassem, Mohamed A. Zakaria

Research output: Contribution to journalArticle

1 Citation (Scopus)

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)aminothio-carbohydrazide (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. The13C NMR spectra were recorded with JEOL spectrometer at 125.7 MHz. The assignments of1H NMR spectra were based on chemical-shift correlation DQFCOSY spectra, while the assignment of13C 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 bi-heterocycles and nucleosides was studied. The conformations of the acyclic alditolyl residues or the acyclic C-nucleosides 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.

Original languageEnglish
Pages (from-to)1005-1013
Number of pages9
JournalCurrent Organic Synthesis
Volume15
Issue number7
DOIs
Publication statusPublished - 1 Jan 2018

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Nucleosides
Conformations
Derivatives
Nuclear magnetic resonance
Dimethyl Sulfoxide
Aldehydes
Chemical shift
Thiosemicarbazones
Sugars
Spectrometers
Silica Gel
Cyclization
Ultraviolet Rays
Thin Layer Chromatography
Plastics
Thin layer chromatography
Methanol
Forms (concrete)
Spectrophotometers
Ethanol

Keywords

  • Acyclo C-nucleoside
  • Conformation
  • Hybrid heterocycles
  • N-(1,3-dioxoisoindol-2-yl)aminothiocarbohydrazide
  • Thiadiazoline
  • Thiosemicarbazides

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

Cite this

@article{b03dfae453cf40cba6c1a99155590abe,
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",
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)aminothio-carbohydrazide (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. The13C NMR spectra were recorded with JEOL spectrometer at 125.7 MHz. The assignments of1H NMR spectra were based on chemical-shift correlation DQFCOSY spectra, while the assignment of13C 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 bi-heterocycles and nucleosides was studied. The conformations of the acyclic alditolyl residues or the acyclic C-nucleosides 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.",
keywords = "Acyclo C-nucleoside, Conformation, Hybrid heterocycles, N-(1,3-dioxoisoindol-2-yl)aminothiocarbohydrazide, Thiadiazoline, Thiosemicarbazides",
author = "{El Ashry}, {El Sayed H.} and Awad, {Laila F.} and Mahmoud Nasr and Kassem, {Ahmed A.} and Zakaria, {Mohamed A.}",
year = "2018",
month = "1",
day = "1",
doi = "10.2174/1570179415666180731123111",
language = "English",
volume = "15",
pages = "1005--1013",
journal = "Current Organic Synthesis",
issn = "1570-1794",
publisher = "Bentham Science Publishers B.V.",
number = "7",

}

TY - JOUR

T1 - 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

AU - El Ashry, El Sayed H.

AU - Awad, Laila F.

AU - Nasr, Mahmoud

AU - Kassem, Ahmed A.

AU - Zakaria, Mohamed A.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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)aminothio-carbohydrazide (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. The13C NMR spectra were recorded with JEOL spectrometer at 125.7 MHz. The assignments of1H NMR spectra were based on chemical-shift correlation DQFCOSY spectra, while the assignment of13C 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 bi-heterocycles and nucleosides was studied. The conformations of the acyclic alditolyl residues or the acyclic C-nucleosides 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.

AB - 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)aminothio-carbohydrazide (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. The13C NMR spectra were recorded with JEOL spectrometer at 125.7 MHz. The assignments of1H NMR spectra were based on chemical-shift correlation DQFCOSY spectra, while the assignment of13C 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 bi-heterocycles and nucleosides was studied. The conformations of the acyclic alditolyl residues or the acyclic C-nucleosides 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.

KW - Acyclo C-nucleoside

KW - Conformation

KW - Hybrid heterocycles

KW - N-(1,3-dioxoisoindol-2-yl)aminothiocarbohydrazide

KW - Thiadiazoline

KW - Thiosemicarbazides

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U2 - 10.2174/1570179415666180731123111

DO - 10.2174/1570179415666180731123111

M3 - Article

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EP - 1013

JO - Current Organic Synthesis

JF - Current Organic Synthesis

SN - 1570-1794

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