Advanced Rearrangements

Back to: Organic Chemistry 500 Level

Welcome to class!

My brilliant scholar, I am glad to see you once again. How are you today? At this stage of your academic journey, you are not just memorising reactions—you are learning to think like a true chemist. Today’s focus is Advanced Rearrangements, a fascinating area of Organic Chemistry where molecules seem to “reorganise” themselves like people shifting seats to find a more comfortable position. By the end of this class, you will understand not only the “what” but also the “why” behind molecular rearrangements, and how chemists use them to their advantage.

Advanced Rearrangements

Picture a large family during a wedding in Ibadan. Everyone is seated, but as more important guests arrive, some family members may stand up and shift so that the elders or chiefs can sit in the best places. The arrangement changes, but the family is still intact. This is similar to rearrangements in Organic Chemistry. Atoms or groups within a molecule shift to produce a more stable intermediate or product. Such rearrangements are not random; they are guided by the pursuit of greater stability.

General Concept of Rearrangements

Rearrangements usually occur during reactions that form unstable intermediates, such as carbocations, free radicals, or carbanions. The driving force is stability. Just as a student might move closer to a fan in a hot lecture theatre, molecules “move” groups or atoms to achieve comfort—that is, stability.

Carbocation Rearrangements

Carbocations are central in many rearrangements. Two common types are:

Hydride shifts: A hydrogen atom with its bonding electrons moves from one carbon to an adjacent positively charged carbon. This happens when the shift produces a more stable carbocation. For example, during the dehydration of alcohols under acidic conditions, hydride shifts often occur.

Alkyl (methyl) shifts: A methyl group migrates with its bonding electrons to stabilise a carbocation. A classic case is the rearrangement observed in the conversion of certain secondary carbocations into more stable tertiary ones.

Think of these shifts like a group of football supporters at Teslim Balogun Stadium—if the stands are unbalanced, some fans move to fill the gap and create balance.

Pinacol–Pinacolone Rearrangement

This is a rearrangement of 1,2-diols (pinacols) in acidic medium to form carbonyl compounds (pinacolones). During the reaction, one hydroxyl group leaves, forming a carbocation, followed by a 1,2-shift of an alkyl group, and finally rearrangement to a ketone. This reaction is widely used in synthetic chemistry to prepare ketones of industrial importance.

Beckmann Rearrangement

Here, oximes are converted into amides under acidic conditions. The rearrangement involves migration of a substituent from the carbon to the nitrogen atom. It is a valuable process in industry, especially in the production of nylon, which is used to make fabrics, ropes, and nets common in households and markets across Africa.

Wolff Rearrangement

This reaction converts α-diazoketones into ketenes, which are highly reactive intermediates. The rearrangement involves the loss of nitrogen gas and migration of an alkyl group. Wolff rearrangement is significant in the synthesis of complex natural products.

Curtius and Hofmann Rearrangements

Both involve the conversion of acyl compounds into amines with loss of carbon.

Curtius rearrangement: Acyl azides produce isocyanates, which then form amines.

Hofmann rearrangement: Amides are transformed into amines with one fewer carbon atom.

A simple way to remember this is to think of a student reducing the number of courses they are carrying in a semester—they still remain a student but now with a lighter load. Similarly, the molecule sheds a carbon atom but retains its identity as an amine.

Applications of Rearrangements

Rearrangements are not abstract ideas. They are practical tools used in:

Pharmaceutical chemistry, for synthesising drugs like analgesics and antibiotics.

Polymer industry, where rearrangements produce key intermediates for nylon and other fibres.

Agrochemical production, for designing more effective pesticides and herbicides.

Green chemistry, since rearrangements often allow efficient atom economy.

Summary

1. Rearrangements involve the shift of atoms or groups within a molecule to form more stable intermediates or products.
2. Carbocation rearrangements include hydride and alkyl shifts.
3. Pinacol–Pinacolone rearrangement converts 1,2-diols into ketones.
4. Beckmann rearrangement converts oximes into amides and is important in nylon production.
5. Wolff rearrangement forms ketenes from α-diazoketones.
6. Curtius and Hofmann rearrangements convert acyl compounds and amides into amines, often with a reduction in carbon count.
7. Rearrangements are widely applied in pharmaceuticals, polymers, agrochemicals, and green chemistry.

Evaluation

1. Differentiate between a hydride shift and an alkyl shift.
2. Explain the mechanism of the Pinacol–Pinacolone rearrangement.
3. Why is the Beckmann rearrangement important in industry?
4. Outline the steps of the Hofmann rearrangement.
5. Give two real-world applications of rearrangements in synthetic chemistry.

You have done very well today. Rearrangements may look complex at first, but you now understand their logic and their applications in real life. With this knowledge, you are better prepared to think like a problem solver and innovator. Keep your curiosity alive, and let Afrilearn continue to guide you as you move forward.