Reactivity of Cations and Zwitterions Formed in Photochemical and Acid-Catalyzed Reactions from m-Hydroxycycloalkyl-Substituted Phenol Derivatives

Abstract

Three m-substituted phenol derivatives, each with a labile benzylic alcohol group and bearing either protoadamantyl 4, homoadamantyl 5, or a cyclohexyl group 6, were synthesized and their thermal acid-catalyzed and photochemical solvolytic reactivity studied, using preparative irradiations, fluorescence measurements, nanosecond laser flash photolysis, and quantum chemical calculations. The choice of m-hydroxy-substitution was driven by the potential for these phenolic systems to generate m-quinone methides on photolysis, which could ultimately drive the excited-state pathway, as opposed to forming simple benzylic carbocations in the corresponding thermal route. Indeed, thermal acid-catalyzed reactions gave the corresponding cations, which undergo rearrangement and elimination from 4, only elimination from 5, and substitution and elimination from 6. On the other hand, upon photoexcitation of 4-6 to S1 in a polar protic solvent, proton dissociation from the phenol, coupled with elimination of the benzylic OH (as hydroxide ion) gave zwitterions (formal m-quinone methides). The zwitterions exhibit reactivity different from the corresponding cations due to a difference in charge distribution, as shown by DFT calculations. Thus, protoadamantyl zwitterion has a less nonclassical character than the corresponding cation, so it does not undergo 1,2-shift of the carbon atom, as observed in the acid-catalyzed reaction.

In vitro investigation of the antimicrobial activity of a series of lipophilic phenols and naphthols

“…(8) was prepared from 7 by treatment with sodium thiolate in 90 % yield according to the published procedure. 19,31 Characterization of product 8 compares well with literature(mp = 162-164°C). …”

“…30 (7) was prepared in a Grignard reaction from homoadamantan-4-one and 3-bromanisol in 67 % yield according to the published procedure. 31 Characterization of product 7 compares well with literature (mp = 130-132°C). (8) was prepared from 7 by treatment with sodium thiolate in 90 % yield according to the published procedure.…”

Synthesis of 1,2-Disubstituted Adamantane Derivatives by Construction of the Adamantane Framework

“…The zwitterion 178 stabilizes the positive charge of the benzylic cation through conjugation with the phenoxide anion, diminishing its carbonium (bridged) character typical for the protoadamantyl systems, prohibiting the rearrangement to adamantane, leading to substitution products instead. The protonated phenol species during solvolysis still maintains its delocalized character, giving rearranged products [93].…”

The controversy about nonclassical ions: Finished too early?

“…Nonclassical carbocation stabilization can generally occur in 1,n‐alkyl shifts and has been identified, eg, in homododecahedryl cation rearrangements, in intermediates in catalysis with gold, and with other electron‐deficient systems such as cyclopropylnitrenium or allylnitrenium intermediates . Nonclassical delocalization can also contribute in protonated cyclopropane intermediates, in photochemical and thermal acid‐catalyzed ring opening of polycycles, in γ‐silyl‐substituted norbornyl carbocations, or in intramolecular cyclopropylmethylation reactions . Charge delocalization plays also a well‐known role in the chemistry of cyclopropylcarbinyl/cyclobutyl cations …”