The Six Pillars of Organic Chemistry

A few weeks ago Jeremy at The Chemistry Blog wrote a post called  “Common Student Difficulties in Organic Chemistry”. Since I was flying home for vacation at the time, I missed out  the discussion, but buried in the comment section was a reference to a recent article by Joseph J. Mullins of Le Moyne College in Syracuse NY called “The Six Pillars of Organic Chemistry” [J Chem Ed, 2008, p. 83 – behind a paywall, but most academic institutions will have it].

Paraphrasing the authors words, the “six pillars” aren’t meant to represent all the concepts required for organic chemistry or to define precisely what concepts were meant to be included, but instead provide a framework. Prof. Mullins’ “six pillars” are the following:

1. Electronegativity – in an example provided, going across a period  leads to decreasing nucleophilicity with increasing electronegativity. For example, nucleophilicity follows the following order:
2. Polar covalent bonding – when bonds form between atoms of unequal electronegativity, the resulting dipole has a positively charged terminus and a negatively charged terminus, which will provide insight into its preferred mode of chemical reactivity. So in the above example, the C-Cl bond is polarized whereas the C-H bonds (C and H having relatively similar electronegativities) are not, resulting in selective breakage of the carbon-halogen bond during the SN2 instead of the carbon-hydrogen bonds.
3. Steric effects – the rate of the SN2 is greatly affected by the presence of neighboring bulky groups. So the trend for the above reaction would be:
4. Inductive effects. The author gives the example of Markovnikoff’s rule as an example of inductive effects, where increasing substitution on carbon leads to increasing inductive stabilization of the carbocation [he also notes that hyperconjugation, a more fundamentally sound explanation, can be covered in the resonance section, below].
5. Resonance – resonance effects are widespread in organic chemistry. One example is that they explain the selective bromination of cyclohexene at the allylic position under free-radical conditions, versus competing bromination at the secondary (or vinylic positions). Another example is the planarity of peptide bonds due to the π donation of electrons into the carbonyl π* orbital.
6. Aromaticity – Aromaticity is an important driving force in chemical reactions and a powerful stabilizing influence on molecules. The decreased reactivity of benzene in bromination reactions versus, say, cyclohexene is an extension of resonance stabilization, which helps to explain why tryptophan is not considered a basic amino acid even though (like lysine) it contains a nitrogen – in tryptophan, the nitrogen lone pair is tied up in the π system.

I really enjoy thinking about things like this. Overall I think it’s extremely helpful to develop a framework that boils down organic chemistry into a short set of useful principles. That’s essentially the goal of this site, after all. I think the ideal set will, to some extent, depend on the professor’s audience of students. In some undergraduate organic chemistry courses (particularly community colleges) the first half consists of lessons on chemical structure and reactivity followed by a strong dose of biochemistry. I’m not certain, but I think this the type of course that Prof. Mullins is teaching. In more research-oriented schools,  where the second half of the course is essentially a rapid series of new reagents and transformations, students are stuggling to drink from a firehose. It would probably be more helpful in these circumstances to include principles that more explicitly assist with understanding the driving forces of most reactions in organic chemistry.  “Nucleophile attacks electrophile“, for example, is an extremely simplifying way of looking at chemical reactions, and recognizing the patterns of electron flow helps to avoid an excessive reliance on memorization.

I think the best quote of the article is the following:

“It is therefore sensible when teaching the subject to remember to explicitly refer to the underlying principles, and not to assume that learners are recognizing the physical forces”.

Bingo. I make this mistake all the time. Sage advice.

For educators reading this:  what would be your “six pillars”?