A synthetic route to novel 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)(thio)barbiturates

João L. Serrano, Eunice Cavalheiro, Sónia Barroso, Maria J. Romão, Samuel Silvestre, Paulo Almeida

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

2,1-Benzisoxazoles, also called anthranils, are one of the two types of aromatic bicyclic heterocycles having a benzene ring fused with an isoxazole, which are particularly recognized as valuable intermediates in organic synthesis. Nevertheless several methods can be found in the literature to prepare 2,1-benzisoxazoles, we herein report a new, efficient, simple, mild, and alternative procedure to prepare 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)barbiturates in moderate to good yields (51–82%). All the novel benzisoxazoles showed spectral data fully consistent with the assigned structures, which were unequivocally confirmed by single crystal X-ray analysis. A possible mechanism of the reaction is proposed. In addition, a screening of the bioactivity of these benzisoxazoles as xanthine oxidase inhibitors, antioxidants, and cytotoxic compounds was performed. The benzisoxazole formed from barbituric acid revealed moderate xanthine oxidase inhibitory effects (IC50 = 22.10 μM).

Original languageEnglish
Pages (from-to)990-995
Number of pages6
JournalComptes Rendus Chimie
Volume20
Issue number11-12
DOIs
Publication statusPublished - 1 Nov 2017

Fingerprint

Barbiturates
Xanthine Oxidase
Isoxazoles
X ray analysis
Bioactivity
Benzene
Antioxidants
Screening
Single crystals
Acids
Oxidoreductases
barbituric acid

Keywords

  • 2,1-Benzisoxazoles
  • Anthranils
  • Barbiturates
  • Single crystal X-ray
  • Xanthine oxidase inhibition

Cite this

Serrano, João L. ; Cavalheiro, Eunice ; Barroso, Sónia ; Romão, Maria J. ; Silvestre, Samuel ; Almeida, Paulo. / A synthetic route to novel 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)(thio)barbiturates. In: Comptes Rendus Chimie. 2017 ; Vol. 20, No. 11-12. pp. 990-995.
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A synthetic route to novel 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)(thio)barbiturates. / Serrano, João L.; Cavalheiro, Eunice; Barroso, Sónia; Romão, Maria J.; Silvestre, Samuel; Almeida, Paulo.

In: Comptes Rendus Chimie, Vol. 20, No. 11-12, 01.11.2017, p. 990-995.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A synthetic route to novel 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)(thio)barbiturates

AU - Serrano, João L.

AU - Cavalheiro, Eunice

AU - Barroso, Sónia

AU - Romão, Maria J.

AU - Silvestre, Samuel

AU - Almeida, Paulo

N1 - sem pdf conforme despacho. FEDER funds through the POCI-COMPETE 2020-Operational Programme Competitiveness and Internationalisation in Axis I-Strengthening research, technological development and innovation (Project POCI-01-0145-FEDER-007491) and National Funds by FCT-Foundation for Science and Technology (Project UID/Multi/00709/2013). The SCXR determinations were performed at UCIBIO/FCT-NOVA, financed by national funds from FCT/MEC (UID/Multi/04378/2013), and cofinanced by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728)

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 2,1-Benzisoxazoles, also called anthranils, are one of the two types of aromatic bicyclic heterocycles having a benzene ring fused with an isoxazole, which are particularly recognized as valuable intermediates in organic synthesis. Nevertheless several methods can be found in the literature to prepare 2,1-benzisoxazoles, we herein report a new, efficient, simple, mild, and alternative procedure to prepare 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)barbiturates in moderate to good yields (51–82%). All the novel benzisoxazoles showed spectral data fully consistent with the assigned structures, which were unequivocally confirmed by single crystal X-ray analysis. A possible mechanism of the reaction is proposed. In addition, a screening of the bioactivity of these benzisoxazoles as xanthine oxidase inhibitors, antioxidants, and cytotoxic compounds was performed. The benzisoxazole formed from barbituric acid revealed moderate xanthine oxidase inhibitory effects (IC50 = 22.10 μM).

AB - 2,1-Benzisoxazoles, also called anthranils, are one of the two types of aromatic bicyclic heterocycles having a benzene ring fused with an isoxazole, which are particularly recognized as valuable intermediates in organic synthesis. Nevertheless several methods can be found in the literature to prepare 2,1-benzisoxazoles, we herein report a new, efficient, simple, mild, and alternative procedure to prepare 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)barbiturates in moderate to good yields (51–82%). All the novel benzisoxazoles showed spectral data fully consistent with the assigned structures, which were unequivocally confirmed by single crystal X-ray analysis. A possible mechanism of the reaction is proposed. In addition, a screening of the bioactivity of these benzisoxazoles as xanthine oxidase inhibitors, antioxidants, and cytotoxic compounds was performed. The benzisoxazole formed from barbituric acid revealed moderate xanthine oxidase inhibitory effects (IC50 = 22.10 μM).

KW - 2,1-Benzisoxazoles

KW - Anthranils

KW - Barbiturates

KW - Single crystal X-ray

KW - Xanthine oxidase inhibition

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DO - 10.1016/j.crci.2017.10.002

M3 - Article

VL - 20

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JO - Comptes Rendus Chimie

JF - Comptes Rendus Chimie

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