Reaction Troubleshooting

Reaction troubleshooting is the habit of comparing the expected mechanism with the observed evidence.

Use this page when a reaction does not match the planned outcome.

First classify the problem

Observation	First question	Likely direction
Starting material remains	Is the reaction too slow or blocked?	Check temperature, solvent, reagent quality and sterics.
Many new TLC spots	Is the substrate reacting by a competing pathway?	Check acid/base strength, water, oxidation state and heat.
No visible change	Is the monitoring method sensitive enough?	Check stain, UV response, co-spot and solvent system.
Product appears then fades	Is the product unstable under the conditions?	Check quench timing, work-up pH, heat and air sensitivity.
Unexpected major product	Was the original selectivity assumption wrong?	Check substrate class, leaving group, nucleophile/base and mechanism.

Mechanism audit

Ask these questions in order:

1. What reactive site is most electrophilic or nucleophilic?
2. Is the reagent acting as a nucleophile, base, acid, oxidant or reductant?
3. Is the substrate sterically open enough for the proposed pathway?
4. Does the solvent stabilise ions, transition states or charged reagents?
5. Is the reaction reversible under the conditions?
6. Is there a more stable intermediate that can rearrange?

Common organic chemistry forks

Fork	Pushes one way	Pushes the other way
SN1 vs SN2	Stable carbocation, weak nucleophile, polar protic solvent.	Primary substrate, strong nucleophile, low steric hindrance.
Substitution vs elimination	Good nucleophile, lower temperature, less hindered base.	Strong bulky base, heat, beta hydrogen alignment.
Mild vs strong reduction	Aldehyde or ketone with NaBH4-level reactivity.	Ester, acid chloride or carboxylic acid needing LiAlH4-level reactivity.
Controlled vs over-oxidation	Anhydrous PCC-style conditions for aldehyde target.	Aqueous strong oxidant when carboxylic acid is acceptable.

TLC triage

If TLC is the main evidence, check:

• lane labels are not swapped
• solvent front was marked before evaporation
• sample was not overloaded
• co-spot confirms whether starting material remains
• visualisation method can actually show the compound
• Rf comparison uses the same plate and solvent system

Before changing conditions

Write down:

• the intended transformation
• the expected starting-material spot
• the expected product spot or polarity shift
• the most likely side reaction
• the single variable you are changing

Only change one major variable at a time when you need interpretable evidence.

Related pages

• TLC Reaction Monitoring
• Work-up and Extraction Guide
• Substitution and Elimination Map
• Reagent Selection Map

Quick summary

Troubleshooting works best when it is evidence-led.

Classify the observation, audit the mechanism and change one interpretable variable.