Dynamic Combinatorial Chemistry of Esters and Benzoins: Distillative Self-Sorting and Macrocyclization

Date

2015-08

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Abstract

Dynamic combinatorial libraries (DCLs) are collections of structurally related compounds that can interconvert through reversible chemical reaction(s). Such reversibility endows DCLs with adaptability to external stimuli, as rapid interconversion allows quick expression of those DCL components, which best respond to the disturbing stimulus. Chapter one focuses on the comparison between thermodynamically and kinetically controlled phenomena that occur within DCLs. Specifically, it will describe self-sorting under the influence of reversible and irreversible chemical and physical stimuli. Metal alkoxides, such as NaOt-Bu or Ti(OBu)4, can initiate acyl exchange within complex ester libraries. Reactive distillation of such DCLs isolates the most volatile ester at the expense of the less volatile library members that share a constituent with it. This process can be iteratively repeated to yield up to four industrially relevant esters as pure products from a single reaction setup. Esters are also volatile and pleasantly smelling compounds, commonly used as food additives. Using Ti(OBu)4-catalyzed acyl exchange, we demonstrate a scent transmutation experiment, in which two fragrant esters swap their acyl and alkoxy substituents and are, during the course of a reactive distillation, quantitatively converted into two different esters with distinct fragrance properties. We view this simple and appealing experiment as highly suitable for instructional use, since it can be used to teach the concepts of chemical equilibrium, distillation, transesterifcation, dynamic combinatorial chemistry, and the industrially relevant process of reactive distillation. Using cyanide-assisted benzoin condensation of isophthaldehyde terephthalaldehyde, we first prepared cyclotribenzoin and cyclotetrabenzoin. Cyclotribenzoin is a cone-shaped macrocycle whose three benzene rings define a cuplike cavity, while six of its C–H bonds convergently point in the opposite direction. This combination of convergently oriented cation- and anion-binding groups, coupled with an exceedingly simple synthesis, promises to make cyclotribenzoin an appealing platform for supramolecular chemistry studies. Cyclotetrabenzoin is a square shape-persistent macrocycle ornamented with four α-hydroxyketone functionalities pointing away from the central cavity, whose dimensions are 6.9×6.9 Å. In the solid state, these functional groups extensively hydrogen bond, resulting in a microporous three-dimensional organic framework with one-dimensional nanotube channels. This material exhibits permanent porosity, with a Langmuir surface area of 52 m2g−1.

Description

Keywords

Reactive distillation, Cyclobenzoin

Citation

Portions of this document appear in: Ji, Qing, Rio Carlo Lirag, and Ognjen Š. Miljanić. "Kinetically controlled phenomena in dynamic combinatorial libraries." Chemical Society Reviews 43, no. 6 (2014): 1873-1884. And in: Ji, Qing, and Ognjen Š Miljanić. "Distillative self-sorting of dynamic ester libraries." The Journal of organic chemistry 78, no. 24 (2013): 12710-12716. And in: Ji, Qing, Loi H. Do, and Ognjen Š. Miljanić. "Cyclotribenzoin." Synlett 26, no. 11 (2015): 1625-1627. And in: Ji, Qing, Ha TM Le, Xiqu Wang, Yu‐Sheng Chen, Tatyana Makarenko, Allan J. Jacobson, and Ognjen Š. Miljanić. "Cyclotetrabenzoin: Facile Synthesis of a Shape‐Persistent Molecular Square and Its Assembly into Hydrogen‐Bonded Nanotubes." Chemistry–A European Journal 21, no. 48 (2015): 17205-17209.