The specific targeting of covalent bonds in a local, anisotropic fashion using mechanical methods offers useful opportunities to direct chemical reactivity down otherwise prohibitive pathways. Here, we report that embedding the highly inert 1,2,3-triazole moiety (which is often prepared using the canonical "click" coupling of azides and alkynes) within a poly(methyl acrylate) chain renders it susceptible to ultrasound-induced cycloreversion, as confirmed by comprehensive spectroscopic and chemical analyses. Such reactivity offers the opportunity to develop triazoles as mechanically labile protecting groups or for use in readily accessible materials that respond to mechanical force.

While the field of polymer mechanochemistry has traditionally focused on the use of mechanical forces to accelerate chemical processes, theoretical considerations predict an underexplored alternative: the suppression of reactivity through mechanical perturbation. Here, we use electronic structure calculations to analyze the mechanical reactivity of six mechanophores, or chemical functionalities that respond to mechanical stress in a controlled manner. Our computational results indicate that appropriately directed tensile forces could attenuate (as opposed to facilitate) mechanochemical phenomena. Accompanying experimental studies supported the theoretical predictions and demonstrated that relatively simple computational models may be used to design new classes of mechanically responsive materials. In addition, our computational studies and theoretical considerations revealed the prevalence of the anti-Hammond (as opposed to Hammond) effect (i.e., the increased structural dissimilarity between the reactant and transition state upon lowering of the reaction barrier) in the mechanical activation of polyatomic molecules.

The burgeoning field of polymer mechanochemistry has garnered significant interest in recent years. Mechanochemical transformations are those that are promoted by exogenous forces, and polymer mechanochemistry concentrates on the use of polymer chains to translate mechanical forces to chemical systems. Acoustic fields, particularly ultrasound, have proven to be highly efficient progenitors of tensile stresses within macromolecules and are frequently used to facilitate mechanochemical phenomena. Mechanochemical activation often arises when mechanophores, or functional groups that respond to mechanical perturbation in a controlled manner, are appropriately positioned within a polymer chain to experience tensile forces. A variety of interesting transformations have been realized when well‐designed mechanophores have been properly outfitted with polymer chains, including: thermally inaccessible isomerizations and cycloreversions, symmetry‐forbidden electrocyclic ring openings and activation of latent catalysts. Herein, the chemistry of known mechanophores is summarized and augmented with implications for new opportunities in synthesis and materials science. The focus of this mini‐review is limited to mechanophores that have been specifically adapted for polymer mechanochemistry under acoustic activation. Copyright © 2012 Society of Chemical Industry

Mechanically responsive polymers harness mechanical energy to facilitate unique chemical transformations and bestow materials with force sensing (e.g., mechanochromism) or self-healing capabilities. A variety of solution- and solid-state techniques, covering a spectrum of forces and strain rates, can be used to activate mechanically responsive polymers. Moreover, many of these methods have been combined with optical spectroscopy or chemical labeling techniques to characterize the products formed via mechanical activation of appropriate precursors in situ. In this tutorial review, we discuss the methods and techniques that have been used to supply mechanical force to macromolecular systems, and highlight the advantages and challenges associated with each.

A number of recent studies have shown that mechanical stress can significantly lower or raise the activation barrier of a chemical reaction. Within a common approximation due to Bell [Science 200, 618 (1978)], this barrier is linearly dependent on the applied force. A simple extension of Bell's theory that includes higher order corrections in the force predicts that the force-induced change in the activation energy will be given by -FΔR - ΔχF(2)∕2. Here, ΔR is the change of the distance between the atoms, at which the force F is applied, from the reactant to the transition state, and Δχ is the corresponding change in the mechanical compliance of the molecule. Application of this formula to the electrocyclic ring-opening of cis and trans 1,2-dimethylbenzocyclobutene shows that this extension of Bell's theory essentially recovers the force dependence of the barrier, while the original Bell formula exhibits significant errors. Because the extended Bell theory avoids explicit inclusion of the mechanical stress or strain in electronic structure calculations, it allows a computationally efficient characterization of the effect of mechanical forces on chemical processes. That is, the mechanical susceptibility of any reaction pathway is described in terms of two parameters, ΔR and Δχ, both readily computable at zero force.

Poly(methyl acrylate) chains of varying molecular weight were grown from 1,4- as well as 1,5-disubstituted 1,2,3-triazoles. Irradiating acetonitrile solutions of these polymers with ultrasound resulted in the formal cycloreversion of the triazole units, as determined by a variety of spectroscopic and chemical labeling techniques. The aforementioned reactions were monitored over time, and the rate constant for the cycloreversion of the 1,5-disubstituted triazole was measured to be 1.2 times larger than that of the 1,4-disubstituted congener. The difference was attributed to the increased mechanical deformability of the 1,5-regioisomer as compared to the 1,4-isomer. This interpretation was further supported by computational studies, which employed extended Bell theory to predict the force dependence of the activation barriers for the cycloreversions of both isomers.

The strategic incorporation of the trifluoromethyl (CF3) functionality within therapeutic or agrochemical agents is a proven strategy for altering their associated physicochemical properties (e.g., metabolic stability, lipophilicity, and bioavailability). Electrophilic trifluoromethylation has emerged as an important methodology for installing the CF3 moiety onto an array of molecular architectures, and, in particular, CF3 λ3-iodanes have garnered significant interest because of their unique reactivity and ease of handling. Trifluoromethylations mediated by these hypervalent iodine reagents often require activation through an exogenous Lewis or Brønsted acid; thus, putative intermediates invoked in these transformations are cationic CF3 iodoniums. These iodoniums have, thus far, eluded isolation and investigation of their innate reactivity (which has encouraged speculation that such species cannot be accessed). A more complete understanding of the mechanistic relevance of CF3 iodoniums is paramount for the development of new trifluoromethylative strategies involving λ3-iodanes. Here, we demonstrate that CF3 iodonium salts are readily prepared from common λ3-iodane precursors and exhibit remarkable persistence under ambient conditions. These reagents are competent electrophiles for a variety of trifluoromethylation reactions, and their reactivity is reminiscent of that observed when CF3 iodanes are activated using Lewis acids. As such, our results suggest the mechanistic relevance of CF3 iodonium intermediates in trifluoromethylative processes mediated by λ3-iodanes. The isolation of CF3 iodonium salts also presents the unique opportunity to employ them more generally as mechanistic probes.

In this viewpoint, we highlight the ability of mechanical force to overcome the limitations associated with using thermal or photochemical stimuli to facilitate chemical transformations. Emphasis will be directed toward examples of new chemical reactions that are accessed through externally applied mechanical forces, as these are illustrative of the emerging concept of using polymer chemistry to drive the synthesis of small molecules. In parallel, we offer perspectives on the potential applications of polymer mechanochemistry in the development of novel synthetic strategies.