Chemical Sciences: A Manual for CSIR-UGC National Eligibility Test for Lectureship and JRF/Named Reactions/Demjanov Rearrangement


The Demjanov rearrangement (named after its discoverer Nikolai Demyanov) is the chemical reaction of primary amines with nitrous acid to give rearranged alcohols.[1][2][3] It involves substitution by an OH group with a possible ring expansion.

It is named after the Russian chemist Nikolai Jakovlevich Demjanov (Dem'anov, Demianov) (18611938).[4]

Demjanov Rearrangement Scheme.png

Reaction MechanismEdit

The reaction process begins with diazotization of the amine by nitrous acid. The diazonium group is a good leaving group.

At this point, two possibilities occur. In possibility A, the four membered ring expands to produce a charged five membered ring, thus expelling the nitrogen gas. An water molecule adds to the carbocation, and with one further deprotonation the substituted five membered ring is produced.[5]

A.  

In possibility B, the hydrogen molecule adds directly to the carbon attached to the nitrogen molecule, thus expelling the nitrogen gas in one step. After deprotonation, the substituted four membered ring is produced.[6]

B.  

UsesEdit

The Demjanov rearrangement is extremely useful in producing a 1-carbon ring enlargement in four, five or six membered rings. Ring enlargements are incredibly useful in synthesizing mechanically useful molecules.

It has been shown that the Demjanov reaction is susceptible to regioselectivity. One example of this is a study conducted by D. Fattori looking at the regioselectivity of the Demjanov rearrangement in one-carbon enlargements of naked sugars.[7] It showed that when the an exo methylamine underwent Demjanov nitrous acid deamination, ring enlargement was not produced.

 

However, when the endo methylamine underwent the same conditions, a mixture of rearranged alcohols were produced.

 

Often, the Demjanov rearrangement is followed by deprotonation to produce a cyclic ketone, an incredibly useful molecule for further reactions such as various nucleophilic attacks.

ProblemsEdit

This rearrangement also leads to a substituted, but not expanded, byproduct. Thus it can be difficult to isolate the two products and acquire the desired yield. Also, stereoisomers are produced depending on the direction of addition of the water molecule and other molecules may be produced depending on rearrangements.

Future usesEdit

Current research is exploring the possibilities of various directing groups to influence the selectivity of products in the Demjanov rearrangement, such as tin or silicon.[8]This may lead to increased success with the Demjanov, as it would allow more control in the reaction and increase the desired product yield. The rearrangement is incredibly useful, but using it can sometimes prove ineffective by the difficulty of creating the preferred product. Thus if directing groups are possible, this would greatly improve the applicability of the Demjanov.

VariationsEdit

Tiffeneau-Demjanov RearrangementEdit

The Tiffeneau-Demjanov rearrangement is a variation of the Demjanov rearrangement, and involves both a ring expansion and the production of a ketone by using sodium nitrite and hydrogen cation. Using the Tiffeneau-Demjanov reaction is often advantageous as, while there are rearrangements possible in the products, the reactant always undergoes ring enlargement. As in the Demjanov rearrangement, products illustrate regioselectivity in the reaction. Migratory aptitudes of functional groups dictate rearrangement products.

Use of diazomethaneEdit

Diazomethane also produces ring enlargement, and its reaction is mechanically similar to the Tiffeneau-Demjanov rearrangement.

ReferencesEdit

  1. ^ Demjanov, N. J.; Lushnikov, M. J. Russ. Phys. Chem. 1903, 35, 26.
  2. ^ Demjanov, N. J.; Lushnikov, M. Chem. Zentr. 1903, 1, 828.
  3. ^ Smith, P. A. S.; Baer, D. R. Org. React. 1960, 11, 157. (Review)
  4. ^ Jack Li, Jie. Name Reactions, Third Edition. Berlin; Springer, 2006.
  5. ^ Chow,L; McClure, M; White, J. "Org. Biomol. Chem." "'2004"', "2", 648.
  6. ^ Fattori, D; Henry, S; Vogel, P. "Tetrahedron." "'1993"', "49", 1649.
  7. ^ McKinney, M.A.; Patel, P.P. "J. Org. Chem." "'1973"', "38", 4059.
  8. ^ Kotani, R. "J Org. Chem." "'1965"', "30", 350.
  9. ^ Diamond, J; Bruce, W.F.; Tyson, F.T. "J. Org. Chem." "'1965"', "30", 1840.
  10. ^ Nakazaki, M.; Naemura, K.; Hashimoto, M. "J. Org. Chem." "'1985"', "48", 2289.
  11. ^ Jones, J.B.; Price, P. "Tetrahedron." "'1973"', "29", 1941.
  12. ^ Stern, A.G.; Nickon, A. "J. Org. Chem." "'1992"', "57", 5432.