Reactions: Putting organic chemistry in context, and finding comfort in doctors’ appreciation of the subject

Letters to the editor

Organic chemistry

As a footnote to Mark M. Green’s letter on how to make organic chemistry “be part of understanding the wider world, to be worth knowing” (Jan. 2, 2023, page 3), I wish to illustrate my approach to “a great story to be told.”

For over 50 years I have incorporated five special topics in my sophomore organic chemistry courses starting on day 1. “Chemical Evolution” looks at the simple chemicals and chemical reactions occurring in our universe, Stanley Miller’s exotic prebiotic syntheses of amino acids and peptides, and the simple organic compounds recently found on comets and meteorites. “Insect Pheromones” is introduced during the discussion of alkanes and alkenes, with examples like muscalure, the long-chain alkene of the housefly sex pheromone (a Wittig reaction synthesis), and illustrated by the syntheses of the queen bee pheromone and the Japanese beetle sex pheromone. Halogen addition reactions of alkenes that occur in the ocean via bromonium ions are examples of the natural halogenated alkanes produced by seaweeds (the smell of the ocean), including 1,2-bromochloroalkanes formed when oceanic chloride attacks a bromonium ion generated by bromoperoxidase. “Pesticides and Herbicides” includes the natural insecticides rotenone, caffeine, pyrethrins, and cocaine. Pyrethrins are naturally occurring cyclopropanes, and physostigmine, the “drug of divine justice,” is a natural carbamate. The preparation of DDT and DDD, which includes the cancer drug mitotane, involves electrophilic aromatic substitution and carbonium ion chemistry and illustrates ortho and para ring selectivity. Vietnam defoliants, presented alongside pesticides and herbicides, involve the syntheses of 2,4-D and 2,4,5-T, which illustrate nucleophilic aromatic substitution, benzyne generation, and dioxin formation. “Chemical Carcinogenesis” comprises the metabolism and chemistry of polycyclic aromatic hydrocarbons, benzene versus toluene, aromatic amines, azo dyes, nitrosamines, and natural carcinogens (such as aflatoxin). Protein and nucleic acid chemistry includes “Chemical Warfare,” featuring tear gas, chlorine, phosgene, mustard gas, and organophosphates (such as nerve gas) and the inhibition of acetylcholinesterase. The reaction of pepper spray exemplifies the Michael reaction with nucleic acids, as do the environmental pollutants acrylamide and acrolein.

Each special topic occupies 1–3 lectures of the 30–32 course lectures. The special topics and accompanying slides are intermeshed with these conventional organic chemistry topics: alkene and alkyne electrophilic addition, nucleophilic substitution (S_N1, S_N2), aromatic electrophilic and nucleophilic addition, aryne formation, reductive amination, carbonyl addition and condensation, conjugate addition (Michael reaction), haloform reaction, and Diels- Alder cycloaddition.

It will take some work, but it’s worth the effort.

Gordon W. Gribble
Lebanon, New Hampshire

Much has already been said about the fiasco surrounding the firing of professor Maitland Jones Jr. by New York University as the result of a student petition claiming that his organic chemistry class was too difficult. Without wishing to comment on this case myself, I am reminded of a related aspect of teaching organic chemistry that I suspect others may also have experienced.

Organic chemistry seems to hold a special place in the hearts and minds of most practicing physicians. Some have been left with very positive feelings about this subject, while others have very negative feelings. Both groups of doctors keenly remember how important it was for them to receive good grades in organic chemistry to be admitted to medical school.

Today, when I tell my doctor that I’ve taught organic chemistry, this always draws an immediate response. Some light up with a smile and tell me how much they’ve enjoyed this class, while others frown and offer words to the contrary. When the latter happens, this does give me pause for thought. Is this the right doctor for me? On one occasion, only moments before I was anesthetized for a colonoscopy, my gastroenterologist asked me what class I was teaching at my university. When I told her it was organic chemistry, her face lit up with a smile. Oh, what a relief that was.

Steven L. Regen
Bethlehem, Pennsylvania