What is abnormal Beckmann rearrangement?

Question

What is abnormal Beckmann rearrangement? I read this term in one of my solution papers but I am not able to find relevant literature for the same. Answers linking to some source, or giving the relevant theory are appreciated.

Answer 1

The abnormal Beckmann rearrangement differs from the normal one that there is a nitrile as product of reaction. As compiled by William Reusch (formerly Michigan State University) in his freely accessible virtual textbook organic chemistry, the assumed mechanism of the abnormal Beckmann rearrangement is e.g.,

(image credit)

---

For comparison, the normal Beckmann rearrangement leaves with an amide:

(image credit, same page)

Answer 2

The reaction schemes of both Beckmann and abnormal Beckmann rearrangement has been already provided by @Buttonwood. I am going to explain the mechanism of the reaction and provide some literature to look at.

---

Ketoximes undergo rearrangement reactions involving cleavage of the carbon–carbon bond adjacent to the imino carbon. The normal rearrangement is called Beckmann rearrangement ('normal' Beckmann reaction) leading to amides while the other one is called and the Beckmann fragmentation ('abnormal' Beckmann reaction) leading to nitriles. The mechanism is as follows:

The normal Beckman reaction involves the generation of an incipient carbocation at the carbon atom located anti to the oxime oxygen, which is intercepted by migration to nitrogen to afford a nitrilium ion intermediate, which is subsequently hydrolyzed to yield an amide. The abnormal Beckmann reaction occurs in cases where the adjacent carbon can stabilize positive charge; a carbocation intermediate is formed that undergoes heterolytic fragmentation of the carbon–carbon bond anti to the leaving group to yield a nitrile. The initiating step of both the normal and abnormal Beckmann reactions involve the departure of an oxygen leaving group from nitrogen, with the propensity of a substrate to undergo one or the other transformation dictated by the nature of the anti substituent.

(image source)

You can look at some of the literature where abnormal Beckmann rearrangement is involved:

• Abnormal Beckmann Rearrangement of Spiroketoximes in Polyphosphoric Acid Richard K. Hill and Robert T. Conley, Journal of the American Chemical Society 1960 82 (3), 645-652 DOI: 10.1021/ja01488a037
• Iglesias-Arteaga, Martin & Sandoval-Ramirez, Jesus & Mata-Esma, MY & Viñas, Omar & Bernès, Sylvain. (2004). Abnormal Beckmann rearrangement in 23-hydroxyiminodiosgenin acetate. TETRAHEDRON LETTERS. 45. 4921-4926. 10.1016/j.tetlet.2004.04.119.
• Wang, Cunde & Jiang, Xin & Shi, Haijian & Lu, Jun & Hu, Yuefei & Hu, Hongwen. (2003). Optimization of the Abnormal Beckmann Rearrangement: Application to Steroid 17-Oximes. The Journal of organic chemistry. 68. 4579-81. 10.1021/jo034142y.
• Abnormal Beckmann Rearrangements in Polyphosphoric Acid. I. Benzil Monoxime and Related Oximes, R. T. CONLEY and F. A. MIKULSKI, The Journal of Organic Chemistry 1959 24 (1), 97-100, DOI: 10.1021/jo01083a028
• Krzysztof Błaszczyk, Hanna Koenig, Katarzyna Mel, Zdzisław Paryzek, Abnormal Beckmann rearrangement of steroidal α-chlorocyclobutanone oximes: the fragmentation–substitution reaction, Tetrahedron, Volume 62, Issue 6, 2006 (link)
• The mechanism of the “abnormal” Beckmann rearrangement of triterpenoid oximes G. P. Moss and S. A. Nicolaidis, J. Chem. Soc. D, 1969, 1077-1078, DOI: 10.1039/C29690001077

Answer 3

The Beckmann rearrangement is an acid-mediated isomerization of an oxime (or N-haloimine or nitrone) functional group to corresponding substituted amides (Cyclic oximes or cyclic N-haloimine yield lactams). The rearrangement was discovered by the German chemist, Ernst Otto Beckmann (1853–1923) in 1886 (Ref.1). The rearrangement, which bears its discoverer’s name, is one of the oldest and most familiar transformations in organic chemistry.

The "normal" rearrangement occurs stereospecifically for ketoximes and N-chloro/N-fluoro imines, with the migrating group being anti-periplanar to the leaving group on the nitrogen:

However, certain conditions have been known to racemize the oxime geometry, leading to the formation of both regioisomers during the rearrangement.

There is another reaction that often competes with the "normal" Beckmann rearrangement, which is called "abnormal" Beckmann rearrangement or Beckmann fragmentation (Ref.2 &3). Based on the condition used (e.g., careful selection of promoting reagent and or solvent) and structural properties of the starting oxime (e,g., carbocation stabilizing group substituted at $\alpha$-position), you can get either of products as the major product selectively:

As shown in the above scheme, the cyclohexanone oxime (when $\ce{R = H}$) would give primary carbocation, if it undergoes "abnormal" Beckmann rearrangement or fragmentation by opening the ring and subssequently making a nitrile group. because it is not stable, it is not posible to undrgo this path and gives corresponding lactam as the product al most exclusively by "normal" Beckmann rearrangement.

The cyclobutyl ketoxime, on the otherhans, consist of two methyl groups at $\alpha$-carbon and one more methyl group at $\alpha'$-carbon. As shiown, the $\alpha$-carbon with two methyl groups would give a tertiary carbocation, if it undergoes "abnormal" Beckmann rearrangement or fragmentation by opening the cyclobutyl ring and subsequently making a nitrile group to give stable intermediate, which eventually release a proton to give final nitrile. Because of this situation, ther preferable product under these conditions is through "abnormal" Beckmann rearrangement. Two recent examples of "abnormal" Beckmann rearrangement are given below (Ref.4):

Note that as a rule of thumb, "normal" Beckmann rearrangement happens under acedic conditions while the "abnormal" Beckmann rearrangement needs basic conditions.

References:

1. L. Guy Donaruma and Walter Z. Heldt, "The Beckmann rearrangement (Review)," Organic Reactions 1960, 11, 1–156 (DOI: https://doi.org/10.1002/0471264180.or011.01).
2. Robert E. Gawley, “The Beckmann Reactions: Rearrangements, Elimination–Additions, Fragmentations, and Rearrangement–Cyclizations,” Organic Reactions 1988, 35, 14–24 (DOI: https://doi.org/10.1002/0471264180.or035.01).
3. Richard K. Hill and Robert T. Conley, “Abnormal Beckmann Rearrangement of Spiroketoximes in Polyphosphoric Acid,” J. Am. Chem. Soc. 1960, 82(2), 645–652 (DOI: https://doi.org/10.1021/ja01488a037).
4. Amani Alhifthi, Benjamin L. Harris, Lars Goerigk, Jonathan M. White, and Spencer J. Williams, “Structure–reactivity correlations of the abnormal Beckmann reaction of dihydrolevoglucosenone oxime,” Org. Biomol. Chem. 2017, 15(47), 10105-10115 (DOI: https://doi.org/10.1039/C7OB02499A).