Research Should be Free…as in Freedom!

I’ve always strongly believed that academic research should be freely available. The cost of a subscription to any of the widely available ACS journals is immensely more than enough to pay for compiling and printing the journal; why charge so exorbitantly? You’d think, with all of the subscriptions that entire universities use, the price for the average individual would be much smaller.

Still, the best I can do is start with myself, and put my own research out there.

My independent project for Advanced Organic Lab is the synthesis of a bicyclic diaminopyridine. The procedure is based on a paper by Singh et al. in Organic Letters, which describes a new class of bicyclic and tricyclic acylation catalysts that use a broad set of tied-back orbitals to stabilize the intermediate formed by the catalyst and the acyl compound, enhancing catalysis.

An acylation reaction involves adding carbonyl functionality to a molecule. The Singh paper focuses on catalysis of acylation reactions involving acetic anhydride and tertiary alcohols. The accepted mechanism of the catalysis of these so-called acetylation reactions with the standard catalyst, dimethylaminopyridine (DMAP), involves substitution of the pyridine nitrogen with the acetyl’s carbonyl carbon. The resulting cation (positive at the pyridine nitrogen) pairs with the anion that left the original acetyl compound, typically an anhydride oxyanion or halide. The tertiary alcohol then attacks the carbonyl carbon in the presence of base, yielding the acylated product, the regenerated catalyst, and a salt of the acetyl compound’s leaving group (-) and the conjugate acid of the base (+).

You may be wondering where the other nitrogen atom of DMAP (the dimethyl nitrogen) comes into play in this mechanism. As it turns out, the lone pair orbital on this atom stabilizes the cationic intermediate by resonance and delocalization. This stabilization requires a parallel arrangement of the lone pair orbital and the pyridine p orbitals for maximum effectiveness, so free rotation about the carbon-nitrogen bond hinders catalysis.

But what if the nitrogen atom were somehow tied back so that its lone pair orbital was forced parallel to the pyridine pi system? This is the reasoning behind bicyclic and tricylic DMAP catalysts, which possess two (bicyclic) or three (tricyclic) nitrogen atoms contained in six-membered rings around the pyridine center such that their lone pair orbitals interact optimally with the pyridine pi system. This greatly stabilizes the acetylated cationic intermediate, leading to more effective catalysis.

My goal is to synthesize an unsubstituted precursor to the bicyclic catalysts reported in the Singh paper. In his final bicyclic DMAP catalysts the stabilizing, non-pyridine nitrogens are substituted, but because of time constraints I can’t do that.


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