Thermodynamic vs. Kinetic Control

When a reaction can produce two different products, which one do you actually get? Sometimes the answer is the most stable product (the one with the lowest free energy). Sometimes the answer is the product that forms the fastest, even if it is higher in energy than an alternative. The difference is thermodynamic control vs. kinetic control, and knowing which applies lets you predict products that would otherwise seem contradictory.

The choice hinges on one question: is the reaction reversible under the conditions?

• If yes (usually at high temperature, long reaction time), the products equilibrate and the most stable (lowest-energy) product dominates. This is thermodynamic control.
• If no (usually at low temperature, short reaction time), the products are trapped where they first formed. The fastest-forming product dominates, regardless of stability. This is kinetic control.

The Energy Diagram

Picture a reaction with two possible products, A and B:

• Product A has a lower activation energy (faster to form) but higher product energy (less stable).
• Product B has a higher activation energy (slower to form) but lower product energy (more stable).

At low temperature, most molecules do not have enough energy to get over either barrier quickly, but the lower barrier (for A) wins the race. Once A forms, there is not enough energy to reverse A back to starting material and try again. A dominates.

At high temperature (or long reaction time), enough energy is available to cross both barriers. Both products form AND both products can reverse back to starting material. The system equilibrates, and over time the population shifts toward the lower-energy product B. B dominates.

Classic Example: Addition of HBr to 1,3-Butadiene

This is the textbook example. 1,3-Butadiene is a conjugated diene, and HBr addition gives two possible products:

• 1,2-addition product (3-bromo-1-butene): faster to form. Lower activation energy because the cation intermediate forms on the more stable secondary position closer to the proton attack site.
• 1,4-addition product (1-bromo-2-butene): slower to form but more stable thermodynamically. The C=C double bond in the 1,4-product is internal and disubstituted (more stable than terminal), whereas the 1,2-product has a terminal monosubstituted alkene.

At −80°C: 80% 1,2-product, 20% 1,4-product. Kinetic control.

At 40°C: 20% 1,2-product, 80% 1,4-product. Thermodynamic control.

Same reactants, same reaction mechanism, only the temperature changes. The ratio of products shifts dramatically because at high temperature the reaction becomes reversible and equilibrates to the more stable product.

Enolate Formation: Kinetic vs. Thermodynamic Enolates

Another important example from Ch 7:

Asymmetric ketones (ketones with two different alpha-carbons) have two possible enolates depending on which alpha-H is removed:

• Kinetic enolate: the less substituted alpha-H is removed. Less steric hindrance means faster deprotonation. This enolate has the LESS substituted C=C double bond.
• Thermodynamic enolate: the more substituted alpha-H is removed. More steric hindrance means slower deprotonation but the resulting enolate has the MORE substituted (more stable) C=C.

How do you choose which one forms? Reagent and conditions:

• LDA at −78°C: gives the kinetic enolate. LDA is bulky (cannot reach the more hindered alpha-H), and low temperature prevents equilibration.
• NaH or KH at room temperature: gives the thermodynamic enolate. Less steric block, reversible deprotonation, reaches the more stable product.

This control is important in synthesis and sometimes appears on MCAT passages when an aldol product’s regiochemistry is in question.

Hammond’s Postulate: How Product Stability Affects TS Energy

Hammond’s postulate connects thermodynamics and kinetics:

• For an exothermic (energetically downhill) step, the transition state looks like the starting material (early TS). The TS is low in energy, and product stability has little effect on activation energy.
• For an endothermic (energetically uphill) step, the transition state looks like the product (late TS). The TS is high in energy, and product stability strongly affects activation energy - more stable products have lower activation energies even in this direction.
• For a thermoneutral step, the TS is somewhere in between.

This is why selectivity in radical bromination is so high: the H-abstraction step is roughly thermoneutral/slightly endothermic, with a late TS. The stability of the resulting radical translates directly to the stability of the TS. Chlorination’s H-abstraction is much more exothermic with an early TS, so radical stability matters less and selectivity is low.

Driving Thermodynamically Unfavorable Reactions

Sometimes you need a product that is higher in energy than the starting material (the reaction would “want” to run in reverse). Three standard tricks:

1. Remove the product as it forms (distillation, precipitation). By Le Chatelier’s principle, removing the product drives the equilibrium forward.
2. Couple to an energetically favorable reaction (like ATP hydrolysis in biology). This is the biochemical trick for driving thermodynamically uphill reactions in cells.
3. Use excess of one reagent to push the equilibrium toward the product side.

Energy Diagrams Show It All

A well-drawn energy diagram tells you kinetic vs. thermodynamic at a glance:

• Look at the activation energies of the forward steps. The lowest Ea gives the kinetic product.
• Look at the energies of the final products. The lowest product energy gives the thermodynamic product.
• If these two are different products, the temperature will decide the outcome.

If the lowest Ea and the lowest product energy belong to the same product, there is no conflict - that product is the winner regardless of conditions.

MCAT-Level Summary

For any “two-product” question on the MCAT:

1. Identify the two possible products.
2. Determine which is lower in energy (thermodynamic product).
3. Determine which forms faster (kinetic product - usually has the lower-energy TS).
4. Read the conditions: low T + short time = kinetic product; high T + long time = thermodynamic product; reaction irreversibility = kinetic.
5. Pick the answer consistent with the conditions.

What This Chapter Gives You

You now have the master toolkit for every organic reaction to come:

1. Acids and bases (Brønsted and Lewis).
2. pKa and the rule of equilibrium pointing to the weaker acid.
3. ARIO framework for ranking acidity from structure.
4. Nucleophiles and electrophiles - the partners in every bond-forming step.
5. Leaving groups and how to activate them.
6. Oxidation states of carbon and the OIL RIG ladder.
7. Curved arrow pushing - the grammar of mechanism.
8. Carbocation and carbanion stability rules.
9. Radical stability and the Br₂ vs. Cl₂ selectivity.
10. Kinetic vs. thermodynamic control.

Every reaction chapter in this book (Chs 5 through 10) applies these tools to a specific family of compounds. When you hit a reaction you have never seen before, ask: “Who is the nucleophile? Who is the electrophile? What is the leaving group? What intermediate is most stable? Am I under kinetic or thermodynamic control?” The answers come from this chapter.