No abstract

Scheme 3. Eaton and Cole's Synthesis of Cubane (1)

One prominent aspect of metal organic frameworks (MOFs) is the ability to tune the size, shape, and chemical characteristics of their pores. MOF-5, with its open cubic connectivity of Zn4O clusters joined by two-dimensional, terephthalate linkers, is the archetypal example: both functionalized and elongated linkers produce isoreticular frameworks that define pores with new shapes and chemical environments. The recent scalable synthesis of cubane-1,4-dicarboxylic acid (1,4-H2cdc) allows the first opportunity to explore its application in leading reticular architectures. Herein we describe the use of 1,4-H2cdc to construct [Zn4O­(1,4-cdc)3], referred to as CUB-5. Isoreticular with MOF-5, CUB-5 adopts a cubic architecture but features aliphatic, rather than aromatic, pore surfaces. Methine units point directly into the pores, delivering new and unconventional adsorption locations. Our results show that CUB-5 is capable of selectively adsorbing high amounts of benzene at low partial pressures, promising for future investigations into the industrial separation of benzene from gasoline using aliphatic MOF materials. These results present an effective design strategy for the generation of new MOF materials with aliphatic pore environments and properties previously unattainable in conventional frameworks.

Using a continuous flow reactor, the dehydration of Dfructose and other carbohydrates to 5-(chloromethyl)-furfural (1) is achieved in reaction times as short as 60 s. The biphasic flow process allows for high-yielding multigram scale production of CMF (1) which is obtained with excellent purity after a simple extractive work-up. Efficient conversion of D-fructose into 5-(hydroxymethyl)furfural (2) and levulinic acid (6) is also demonstrated using flow reactor techniques.

Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.