In this article, you are going to learn everything you need to know about Beckmann Rearrangement, including a detailed mechanism of Beckmann Rearrangement.
What is Beckmann Rearrangement?
The acid-catalyzed transformation of a ketoxime to N–substituted amide is known as the Beckmann Rearrangement.
The rearrangement occurs in the presence of a range of acids, including strong acids like H2SO4, Polyphosphoric acid, and acid chlorides like SOCl2, RCOCl, and RSO2Cl. The reaction may be applied to the oximes of both aryl and alkyl ketones and cyclic ketoximes. Aldoximes, on the other hand, normally suffer dehydration to nitrites (RCH = NOH –> RCN) under the condition of the Beckmann rearrangement, and examples of the formation of formamides (HCONHR) from aldoximes are rare.
Few Examples of Beckmann Rearrangement:
Mechanism of the Beckmann Rearrangement
The mechanism of the Beckmann Rearrangement reaction involves the steps as follows.
Step-1: The first step is the protonation of the hydroxyl group in the presence of acid.
Step-2: In this step, migration of the group trans to the protonated hydroxyl group and loss of water occur simultaneously. This leads to the formation of nitrilium ion. Note that it is the slow and rate-determining step.
Step-3: In this step, the nucleophilic attack of water occurs on the electron-deficient carbon atom of the nitrilium ion.
Step-4: In this step, loss of proton occurs, and an imidic acid is formed that readily tautomerizes to give to corresponding N-substituted amide.
The complete step-by-step mechanism is shown in the following diagram:
Which Group Migrates in the Beckmann Rearrangement?
In the Beckmann Rearrangement, the group trans to the -OH group migrates as C=N double bonds can exhibit cis/trans isomerism just like C=C double bonds can.
In the Beckmann Rearrangement of unsymmetrical ketoxime, there are two groups that could migrate. There are also two possible geometrical isomers of an unsymmetrical ketoxime: C=N double bonds can exhibit cis/trans isomerism just as C=C double bonds can. When mixtures of geometrical isomers of oximes are rearranged, mixtures of products result, but the ratio of products mirrors exactly the ratio of geometric isomers in the starting materials – the group that has migrated is in each case the group trans to the OH in the starting material.
For migration to occur, a migrating group has to be able to interact with the a* of the bond to the leaving group, and this is the reason for the specificity here. (Recall Bayer Villiger oxidation). If one of the alkyl chains is branched, more of the oxime with the HO – group anti to the chain will be formed and correspondingly more of the branched group will migrate.
Conditions that allow those double isomers to interconvert can allow either group to migrate. Most protic acids allow the oxime isomers to equilibrate, for example, the tosylated oxime rearranges with full stereospecificity in Al2O3 (the anti methyl group migrates), but with TSOH, equilibration of the oxime geometrical isomers means that either group could migrate in the event the propyl group which is more able to support
Evidence for anti-group Migration in Beckmann Rearrangement
The exclusive migration of the anti-group has been confirmed in many cases e.g., the conversion of 2 – chloro – s – nitro benzophenoneoxime to a chloro nitro benzalide. The configuration of this particular oxime has earliar been established by its ready conversion to a nitro-substituted phenyl benzisooxazole, showing that the nitrated benzene ring lies on the same side of C = N linkage as the – OH group. When this oxime undergoes Beckmann Rearrangement, it is found that the phenyl group rather than the nitrated benzene ring migrates to the nitrogen.
Some Notes on Beckmann Rearrangement
1. If in the Beckmann Rearrangement, the migrating carbon atom of a substrate is asymmetrically substituted, rearrangement occurs with retention of configuration at this asymmetric center. For example, it has been found that rearrangement of an optically active form of the (S, Z)-2-ethyl-1-phenylhexan-1-one oxime (A) to the (S)-N-(heptan-3-yl) benzamide (B) occurs with about 100% retention of configuration at the asymmetric carbon atom. It is also suggested that migrating – group never becomes fully detached from the substrate during the rearrangement, and the rearrangement is intramolecular.
2. Evidence in favor of the intramolecular mechanism of Beckmann Rearrangement: Beckmann Rearrangement is intramolecular and this can be proved by the crossover experiment. When two different
3. Since the rate-determining step in the Beckmann Rearrangement involves the separation of charged species, the rearrangement occurs at a faster rate in polar solvents as the polar solvents facilitate ionization.
4. Evidence for the formation of the carbonyl oxygen atom of the amide product from solvent molecules: When Beckmann Rearrangement is carried out in the presence of isotope-labeled H2O18, the product (amide) is found to contain the labeled oxygen (O18). For example, when benzophenone oxime (A) is treated with PCl5 in H2O18solution, N-phenylbenzamide is found with isotope-labeled oxygen (O18). This observation, therefore, suggests that in this rearrangement, the carbonyl oxygen atom of the amide forms solvent molecules.
Since the migrating – group never becomes fully detached from the substrate during the rearrangement, the migration should proceed in a strictly intramolecular sense. Although there is evidence to suggest that this conclusion is correct for many Beckmann transformations, intermolecular migration has also been observed.
The treatment of a mixture of the oximes (E) and (F) with polyphosphoric acid affords two products (G) & (H) that result from ‘crossover’ migration, in addition to the expected products (I) & (J) of intramolecular rearrangement.
- Beckmann, E. Ber. Dtsch. Chem. Ges. 1886, 19, 988–993.