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Rui Fausto - One of the best experts on this subject based on the ideXlab platform.

  • on the photochemistry of 1 2 benzisoxazole capture of elusive spiro 2h azirine and ketenimine intermediates
    European Journal of Organic Chemistry, 2016
    Co-Authors: Claudio M Nunes, Sandra Pinto, Igor Reva, Rui Fausto
    Abstract:

    The photochemistry of 1,2-benzisoxazole (1) was studied using low-temperature matrix isolation coupled with infrared spectroscopy and quantum chemistry calculations. We identified, for the first time, spiro-2H-azirine 2 and ketenimine 3 as intermediates in the photoisomerization of 1 to 2-cyanophenol (4). These results constitute indirect evidence for the existence of vinylnitrene intermediates in the photochemistry of 1,2-Benzisoxazoles. The potential energy surface (PES) resulting from the N–O bond cleavage of 1 was compared with the respective PES of the parent isoxazole. Calculations at the CBS-QB3 level show that no stabilization is gained for the triplet vinylnitrene upon introduction of a benzene ring fused with isoxazole. However, the energies of 2 and 3 are higher by 13–15 kcal/mol comparing with the 2H-azirine and ketenimine analogs resulting from isoxazole, which explains why they had not been observed before. Our general mechanistic proposal also predicts well the photoisomerizations of 2 and 3 to 4.

  • Photochemistry of 3-amino-1,2-benzisoxazole: unexpected photoisomerization of an amino-spiro-2H-azirine to a 1H-diazirine
    Tetrahedron Letters, 2016
    Co-Authors: Claudio M Nunes, Sandra Pinto, Igor Reva, Rui Fausto
    Abstract:

    Abstract UV irradiation of 3-amino-1,2-benzisoxazole isolated in an argon matrix leads to the formation of an amino-spiro-2 H -azirine. The amino-spiro-2 H -azirine was found to photoisomerize back to 3-amino-1,2-benzisoxazole and also to a 1 H -diazirine, which isomerizes to a carbodiimide. All the reported species were characterized experimentally by IR spectroscopy and confirmed by comparison with theoretical IR spectra. The discovery of the transformation of an amino-spiro-2 H -azirine into a 1 H -diazirine is unprecedented in the chemistry of reactive intermediates.

Yefeng Tang - One of the best experts on this subject based on the ideXlab platform.

Rai-shung Liu - One of the best experts on this subject based on the ideXlab platform.

Yongmin Zhang - One of the best experts on this subject based on the ideXlab platform.

Paulo Almeida - One of the best experts on this subject based on the ideXlab platform.

  • the synthesis of 2 spiroindolin 3 one thio barbiturates from 2 1 Benzisoxazoles a rearrangement promoted by thermal conditions
    Synthesis, 2020
    Co-Authors: Pedro F. Soeiro, João L. Serrano, Samuel Silvestre, Renato E. F. Boto, J A Paixao, Paulo Almeida
    Abstract:

    A new thermal process to prepare spiroindolin-3-ones from 3-substituted 2,1-Benzisoxazoles in good yields (70–85%) is described. The highest yields were observed when microwave irradiation was used. The method does not require the use of any additive or catalyst. A possible reaction mechanism involving a nitrene key intermediate is proposed.

  • Synthesis and process optimization of symmetric and unsymmetric barbiturates C5-coupled with 2,1-Benzisoxazoles
    Molecular Diversity, 2020
    Co-Authors: João L. Serrano, Samuel Silvestre, Pedro F. Soeiro, Melani A. Reis, Renato E. F. Boto, Paulo Almeida
    Abstract:

    Benzisoxazoles represent an important pharmacophore in medicinal chemistry. Recently, an unexpected formation of symmetric 3-substituted 2,1-Benzisoxazoles through reduction of 5-(2-nitrobenzylidene)barbiturates has been described. This reductive intramolecular heterocyclization probably involves a nitroso intermediary. To improve the previous reaction conditions, the nature of the reducing agent and additives, reaction time and solvents were evaluated. By applying the optimized conditions, several symmetric and unsymmetric barbiturates C5-coupled with 2,1-Benzisoxazoles were prepared with an yield of 52–87%. From this set, seven compounds were novel and the unsymmetric nature of the (thio)barbituric acid moiety was explored. For that, the total synthesis, starting from the respective urea or thiourea, was successfully performed, and 11 thiobarbiturates, benzylidene barbiturate and thiobarbiturate precursors are described. Graphical abstract

  • A synthetic route to novel 3-substituted-2,1-Benzisoxazoles from 5-(2-nitrobenzylidene)(thio)barbiturates
    Comptes Rendus Chimie, 2017
    Co-Authors: João L. Serrano, Eunice Cavalheiro, Sónia Barroso, Maria João Romão, Samuel Silvestre, Paulo Almeida
    Abstract:

    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).