Naphtho[1,8-<i>de</i>][1,2]Oxazin-4-ol: Precursor to 1,2,8-Trisubstituted Naphthalenes and 1-Unsubstituted Naphtho[1,2-<i>d</i>]isoxazole 2-Oxide: A Novel Isomerization of the <i>N</i>-Oxide to Nitrile Oxide <i>en Route</i> to Isoxazol(in)es
Naphtho[1,8-<i>de</i>][1,2]oxazin-4-ol and its acyl or benzyl derivatives ring open to various 2,8-dihydroxy-1-naphthonitriles, which, through (de)protection protocols and reduction, afford the target (<i>E</i>)-2-hydroxy-8-methoxy-1-naphthaldehyde. This was converted to its...
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MDPI AG
2023-12-01
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| Online Access: | https://www.mdpi.com/1420-3049/29/1/48 |
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| author | Ioannis E. Gerontitis Petros G. Tsoungas George Varvounis |
| author_facet | Ioannis E. Gerontitis Petros G. Tsoungas George Varvounis |
| author_sort | Ioannis E. Gerontitis |
| collection | DOAJ |
| description | Naphtho[1,8-<i>de</i>][1,2]oxazin-4-ol and its acyl or benzyl derivatives ring open to various 2,8-dihydroxy-1-naphthonitriles, which, through (de)protection protocols and reduction, afford the target (<i>E</i>)-2-hydroxy-8-methoxy-1-naphthaldehyde. This was converted to its corresponding oxime, which was oxidatively <i>o</i>-cyclized with phenyliodine(III) diacetate (PIDA) to 9-methoxynaphtho[1,2-<i>d</i>]isoxazole 2-oxide. The latter, in deuterated DMSO at room temperature, was rearranged to its isomer 2-hydroxy-8-methoxy(naphthalen-1-yl)nitrile oxide. The isomerization was detected by time-course plot <sup>1</sup>H NMR spectroscopy and further identified from its <sup>13</sup>C NMR and HRMS spectra. The nitrile oxide was stable in (non)deuterated DMSO for at least 18 h. A 3,4-bis(2-hydroxy-8-methoxynaphthalen-1-yl)-1,2,5-oxadiazole 2-oxide, as a dimerization product or an isocyanate as a rearrangement isomer, was ruled out, the former by its HRMS spectrum and the latter by its 1,3-dipolar cycloaddition reactions to substituted isoxazoles. |
| first_indexed | 2024-03-08T15:01:42Z |
| format | Article |
| id | doaj.art-bb56f051150b4bb297abd55681ee02af |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T15:01:42Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-bb56f051150b4bb297abd55681ee02af2024-01-10T15:03:58ZengMDPI AGMolecules1420-30492023-12-012914810.3390/molecules29010048Naphtho[1,8-<i>de</i>][1,2]Oxazin-4-ol: Precursor to 1,2,8-Trisubstituted Naphthalenes and 1-Unsubstituted Naphtho[1,2-<i>d</i>]isoxazole 2-Oxide: A Novel Isomerization of the <i>N</i>-Oxide to Nitrile Oxide <i>en Route</i> to Isoxazol(in)esIoannis E. Gerontitis0Petros G. Tsoungas1George Varvounis2Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 451 10 Ioannina, GreeceDepartment of Biochemistry, Hellenic Pasteur Institute, 127 Vas. Sofias Ave., 115 21 Athens, GreeceSection of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 451 10 Ioannina, GreeceNaphtho[1,8-<i>de</i>][1,2]oxazin-4-ol and its acyl or benzyl derivatives ring open to various 2,8-dihydroxy-1-naphthonitriles, which, through (de)protection protocols and reduction, afford the target (<i>E</i>)-2-hydroxy-8-methoxy-1-naphthaldehyde. This was converted to its corresponding oxime, which was oxidatively <i>o</i>-cyclized with phenyliodine(III) diacetate (PIDA) to 9-methoxynaphtho[1,2-<i>d</i>]isoxazole 2-oxide. The latter, in deuterated DMSO at room temperature, was rearranged to its isomer 2-hydroxy-8-methoxy(naphthalen-1-yl)nitrile oxide. The isomerization was detected by time-course plot <sup>1</sup>H NMR spectroscopy and further identified from its <sup>13</sup>C NMR and HRMS spectra. The nitrile oxide was stable in (non)deuterated DMSO for at least 18 h. A 3,4-bis(2-hydroxy-8-methoxynaphthalen-1-yl)-1,2,5-oxadiazole 2-oxide, as a dimerization product or an isocyanate as a rearrangement isomer, was ruled out, the former by its HRMS spectrum and the latter by its 1,3-dipolar cycloaddition reactions to substituted isoxazoles.https://www.mdpi.com/1420-3049/29/1/48naphtholsoximeoxidationisomerizationnitrile oxide1,3-dipolar cycloaddition |
| spellingShingle | Ioannis E. Gerontitis Petros G. Tsoungas George Varvounis Naphtho[1,8-<i>de</i>][1,2]Oxazin-4-ol: Precursor to 1,2,8-Trisubstituted Naphthalenes and 1-Unsubstituted Naphtho[1,2-<i>d</i>]isoxazole 2-Oxide: A Novel Isomerization of the <i>N</i>-Oxide to Nitrile Oxide <i>en Route</i> to Isoxazol(in)es Molecules naphthols oxime oxidation isomerization nitrile oxide 1,3-dipolar cycloaddition |
| title | Naphtho[1,8-<i>de</i>][1,2]Oxazin-4-ol: Precursor to 1,2,8-Trisubstituted Naphthalenes and 1-Unsubstituted Naphtho[1,2-<i>d</i>]isoxazole 2-Oxide: A Novel Isomerization of the <i>N</i>-Oxide to Nitrile Oxide <i>en Route</i> to Isoxazol(in)es |
| title_full | Naphtho[1,8-<i>de</i>][1,2]Oxazin-4-ol: Precursor to 1,2,8-Trisubstituted Naphthalenes and 1-Unsubstituted Naphtho[1,2-<i>d</i>]isoxazole 2-Oxide: A Novel Isomerization of the <i>N</i>-Oxide to Nitrile Oxide <i>en Route</i> to Isoxazol(in)es |
| title_fullStr | Naphtho[1,8-<i>de</i>][1,2]Oxazin-4-ol: Precursor to 1,2,8-Trisubstituted Naphthalenes and 1-Unsubstituted Naphtho[1,2-<i>d</i>]isoxazole 2-Oxide: A Novel Isomerization of the <i>N</i>-Oxide to Nitrile Oxide <i>en Route</i> to Isoxazol(in)es |
| title_full_unstemmed | Naphtho[1,8-<i>de</i>][1,2]Oxazin-4-ol: Precursor to 1,2,8-Trisubstituted Naphthalenes and 1-Unsubstituted Naphtho[1,2-<i>d</i>]isoxazole 2-Oxide: A Novel Isomerization of the <i>N</i>-Oxide to Nitrile Oxide <i>en Route</i> to Isoxazol(in)es |
| title_short | Naphtho[1,8-<i>de</i>][1,2]Oxazin-4-ol: Precursor to 1,2,8-Trisubstituted Naphthalenes and 1-Unsubstituted Naphtho[1,2-<i>d</i>]isoxazole 2-Oxide: A Novel Isomerization of the <i>N</i>-Oxide to Nitrile Oxide <i>en Route</i> to Isoxazol(in)es |
| title_sort | naphtho 1 8 i de i 1 2 oxazin 4 ol precursor to 1 2 8 trisubstituted naphthalenes and 1 unsubstituted naphtho 1 2 i d i isoxazole 2 oxide a novel isomerization of the i n i oxide to nitrile oxide i en route i to isoxazol in es |
| topic | naphthols oxime oxidation isomerization nitrile oxide 1,3-dipolar cycloaddition |
| url | https://www.mdpi.com/1420-3049/29/1/48 |
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