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. 2025 Apr 11;90(14):4946-4953.
doi: 10.1021/acs.joc.5c00021. Epub 2025 Apr 3.

Unusual Rearrangement of a 1,8-Naphthalene Derivative

Asmaa Habib  1 , Estela Sánchez-Santos  1 , Irene Boya Del Teso  1 , José J Garrido-González  1 , Francisca Sanz  2 , Luis Simón  3 , Joaquín R Morán  1 , Ángel L Fuentes de Arriba  1
Affiliations

Unusual Rearrangement of a 1,8-Naphthalene Derivative

Asmaa Habib et al. J Org Chem. .

Abstract

The steric strain between nitro and carboxylic acid groups in an 8-nitro-1-naphthoic acid derivative is able to unexpectedly disrupt the aromaticity of the naphthalene core under mild reaction conditions. The addition of H2O to the aromatic ring of a highly strained naphtho oxazinium intermediate induces the fragmentation of a Csp2-Csp2 bond, with a concomitant rearrangement to yield a conjugated aldehyde. Key intermediates have been characterized, and the X-ray structure of the derivative has been obtained. Density functional theory (DFT) studies were performed to confirm the proposed mechanism.

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Figures

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(A–G) Unusual chemical reactivity and physical properties of 1,8-disubstituted naphthalenes. (H) Unexpected rearrangement obtained in this work.
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1. Synthesis of Aldehyde 4 from Reported Compound 1
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Modeling studies of the phthaloxime aldehyde showing the twisting between the aromatic ring and the substituent supporting the aldehyde.
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2. (Top) Rearrangement of (Z)-3-(Hydroxyimino)­isobenzofuran-1­(3H)-one into N-Hydroxyphthalimide under Basic Conditions Reported in Literature and (Bottom) Rearrangement Found with Aldehyde 4
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(Top) Synthesis of compound 6 from either 4 or 5. (Bottom) Oak Ridge thermal ellipsoid plot (ORTEP) diagram of compound 6. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen atoms are shown as spheres of arbitrary radius.
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3. Key Intermediates Proposed for the Rearrangement of 1,8-Disubstituted Naphthalene 2
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4. Naphtho Oxazole Derivatives with Cytotoxic Activity and the Proposed Nitrenium Intermediate Which Reacts with the Amino Group of DNA Nucleobases
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5. Addition of Potassium Acetate to the Naphthalene Compounds 7 and 10 in the C-7 Position
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6. (Top) Mukaiyama Nitrile Oxide Synthesis and (Bottom) Rearrangement Observed in This Work
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7. Computer Reaction Energy Profile for the Pathway through the Lowest-Energy Transition-State Structure Leading to the Rearranged Aldehyde (Green Background) and the Competing Hydrolysis Reaction (Red Background)
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Minimum energy transition state for the H2PO4 –-catalyzed fragmentation of C7–C8 and N–O bonds.
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