What Bonds Form, What Bonds Break? About a month or so ago I had a big revelation as an instructor. Something that I’d been taking for granted, that was right under my nose. I was spending so much time focusing on the why and how of chemical reactions, that I had neglected to make sure that students understood the what  – in detail.  I was assuming that the vast majority of students could look at a reaction and quickly see which bonds were being formed and which were broken.  I was assuming this because I’d always ask “do you have any questions about this?” and they’d say “no ..read more

One kcal/mol is actually a lot This article discusses the relationship between the equilibrium constant K and the difference in energy ΔG, and explores some applications of the equation towards various examples in organic chemistry. The difference in Gibbs energy ΔG between two species in equilibrium is related to the equilibrium constant K according to the equation Δ G = –RT ln K where R is the gas constant (0.001987 kcal K-1 mol-1) (we will use kcal/mol here – 1 kcal/mol = 4.184 kJ/mol) and T is the temperature (in Kelvin) Two species A and B that are present as a 50:50 ratio at equ ..read more

Identifying Carbons Where Substitution and Elimination Reactions Can Take Place Substitution and elimination reactions need a leaving group in order for them to occur. Look for a good leaving group on the substrate undergoing the substitution or elimination reaction. If there is no good leaving group, then there won’t be a substitution or elimination reaction. It’s that simple. What makes a good leaving group? Review here (See Article: What Makes a Good Leaving Group), but the bottom line is look for halogens and other species that are weak bases. Hydroxyl groups (HO) are poor leaving gr ..read more

Basic Hydrolysis of Esters (Saponification) When esters are treated with sodium hydroxide, they are converted into carboxylate salts, which upon neutralization yield carboxylic acids. This process is called basic hydrolysis of esters, or saponification. Hydrolysis occurs via a two step addition-elimination mechanism (nucleophilic acyl substitution) The carboxylic acid is then deprotonated to give a carboxylate. To get the final carboxylic product, acid is added during the workup step. Table of Contents Basic Hydrolysis of Esters (Saponification) The Mechanism for Basic Hydrolysis Saponifica ..read more

Nucleophilic Acyl Substitution (With Negatively Charged Nucleophiles) Yes, there are a lot of reactions of carboxylic acid derivatives to learn!  In this article we’ll explore what is hands-down the most important pathway: nucleophilic acyl substitution. There is good news, though: with negatively charged nucleophiles nucleophilic acyl substitution tends to follow a simple two-step mechanism (addition-elimination) furthermore, for all intents and purposes, NAS reactions behave a lot like acid-base reactions. If you recall that “stronger acid plus stronger base gives weaker acid plus weak ..read more

No doubt you’ve got some important exams coming up. With that in mind, here’s three simple tactics you can use during exams. 1. Draw partial charges If you get complete brain-lock during a question, try drawing out the partial charges. Ask yourself what the most electronegative atoms in the molecule are. The most electronegative atoms (e.g. oxygen, nitrogen, chlorine) are generally going to have partial negative charges on them, while carbons that they’re bonded to will have partial positive charges. This will help in identifying potential nucleophiles and electrophiles. And sin ..read more

Now that pretty much the entire course has been covered, maybe it’s helpful to go back and highlight some of the key skills you should have in your toolbox as you finish up. As I tell my students, there’s an infinite number of things to learn, but a finite number of important things to learn. Here’s my top 10. Be able to identify the electron-rich and electron poor atoms in a molecule, using electronegativity and resonance. Be able to draw resonance structures, using the “three legal moves“. Be able to draw curved reaction arrows Recognize when molecules are aromatic (and when they’re not) Be ..read more

Peptide bonds: Forming peptides from amino acids with the use of protecting groups Today we’ll go deeper on how to synthesize the most important amides of all – peptides – with an important contribution from protecting group chemistry. Table of Contents What Are Peptide Bonds? The “Proteinogenic” Amino Acids Synthesis of a Dipeptide Without Protecting Groups  Synthesis of a Dipeptide Using A Protecting Group Strategy Synthesis of Longer Peptides – Tripeptides and Tetrapeptides Bonus Topic: Solid-Phase Peptide Synthesis Notes (Advanced) References and Further Reading 1. What Are Peptide ..read more

The Strecker Amino Acid Synthesis The Strecker synthesis is a two-step procedure for the synthesis of amino acids. It begins with the addition of cyanide ion to an imine, forming an alpha-amino nitrile. This is then hydrolyzed (e.g. with strong acid) to give an alpha-amino acid. By varying the R group on the imine, a wide variety of amino acids may be made this way. Table of Contents The Strecker Synthesis of Amino Acids The Two-Part Mechanism of Amino Acids Application: Synthesis of L-DOPA Notes (Advanced) References and Further Reading 1. The Strecker Synthesis of Amino Acids What’s not ..read more

Finally, Some Reactions Of Sugars: Glycosylation And Protection In this post we introduce some simple reactions of sugars, especially glycosylation and protection: Formation of “glycosides” – just a different name for acetals when they exist at the “anomeric” carbon of sugars Hydrolysis of glycosidic bonds (glycosides), which is exactly like hydrolysis of acetals (aqueous acid) Reactions on the -OH groups of sugars, including protecting groups How to “deprotect” the anomeric (C-1) carbon selectively Table of Contents Carbohydrates and Sugars:  Finally, Some Reactions! Reactions At The ..read more