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The mechanism of hydrolysis of aryl ether derivatives of 3-hydroxymethyltriazenes

Carvalho, Emilia; Francisco, Ana Paula; Iley, Jim and Rosa, Eduarda (2005). The mechanism of hydrolysis of aryl ether derivatives of 3-hydroxymethyltriazenes. European Journal of Organic Chemistry, 2005(10) pp. 2056–2063.

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1-Aryl-3-aryloxymethyl-3-methyltriazenes hydrolyse to the
corresponding anilines and phenols by specific-acid-catalysed, general-acid-catalysed and pH-independent mechanisms. All compounds studied exhibit specific- and general acid catalysis, though for 5a general acid catalysis was not observed below a pH of approximately 4, while for compounds 5e,f, such catalysis was absent above a pH of approximately 5. The pH-independent pathway is observed only for those compounds, 5d–f, that contain good aryloxy nucleofugic groups. The specific-acid-catalysed pathway is supported by a solvent deuterium isotope effect (SDIE) of 0.64, consistent with a mechanism involving protonation of the substrate followed by rate-determining unimolecular decomposition of the protonated species. The kH+ values gave rise to a Hammett ρ value of –0.93, reflecting the competing effect of the substituents on the protonation of the substrate and the cleavage of the aryl ether. Correlation of kH+ with the pKa of the phenol leaving group affords a βlg of 0.3. Decomposition of the protonated intermediate proceeds via a triazenyliminium
ion that can be trapped by methanol. The general acid-
catalysed process exhibits an SDIE of 1.43 and Hammett
ρ values of 0.49, 0.84 and 1.0 for reactions catalysed by chloroacetic, formic and acetic acids, respectively. Correlation of kA with the pKa of the acid gave Brønsted α values that diminish from 0.6 for O-aryl systems that are poor nucleofuges (5a,b) to 0.2 for the best nucleofuge (5f), reflecting the different extents of proton transfer required to expel each phenol. Compounds containing powerful nucleofuges exhibit a pH-independent reaction that has an SDIE of 1.1, a Hammett ρ value of 3.4 and a Brønsted βlg value of 1.4. These imply a mechanism involving displacement of the aryloxide leaving group to form a triazenyliminium ion intermediate that again
was trapped as a methyl ether.

Item Type: Journal Item
ISSN: 1434-193X
Keywords: triazenes; aryl ethers; carbinolamine ethers; hydrolysis; Prodrug; kinetics
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 3988
Depositing User: James Iley
Date Deposited: 04 Jul 2006
Last Modified: 02 May 2018 12:36
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