Correlation analysis of the rates of solvolysis of 4-bromopiperidine: A reaction following a Grob fragmentation pathway

Abstract

A Grunwald-Winstein treatment of the specific rates of solvolysis of 4-bromopiperidine gives for aqueous ethanol, methanol, acetone, and dioxane a very good logarithmic correlation against the YBr solvent ionizing power values with a slope (m value) of 0.46±0.02, consistent with the operation of a synchronous Grob fragmentation mechanism. When the organic component of the solvent is 2,2,2-trifluoroethanol (TFE), the data points show a negative deviation, consistent with an appreciable deactivating interaction of the acidic TFE component of the solvent with the lone-pair of electrons present on the nitrogen.

Correlation of the rates of solvolysis of α-bromoisobutyrophenone using both simple and extended forms of the Grunwald-Winstein equation and the application of correlation analysis to related studies

“…The extended Grunwald-Winstein equation [3-6], which has been found to be very useful in its application to the specific rates of solvolysis of a wide variety of substrates, such as phosphorus compounds [34], silicon compounds [35], acid chlorides [36], chloroformate esters [37], chlorothioformate esters [38], and heterocyclic compounds [39], is here applied to the solvolyses of tertiary alpha-substituted ketones, some of which have, contrary to earlier opinions summarized elsewhere [12], been found to be capable of forming carbocations with the charge formally adjacent to the carbonyl group under solvolytic conditions [10-12]. …”

Bioorthogonal Self-Immolative Linker Based on Grob Fragmentation

“…22 Typical conditions use organic solvents, high temperatures, and strong bases. Interestingly, isolated reports have used water as a cosolvent in this reaction, 23,24 which led us to envision that the Grob fragmentation may be performed under milder conditions found in biological environments. To this purpose, we synthesized compounds 1−3 shown in Figure 2.…”