Rearragment

1. BY
Dr. Gurumeet.C.Wadhawa
DEPARTMENT OF CHEMISTRY
K. B. P. College,Vashi,Navimumbai
Tiffeneau–Demjanov
rearrangement

2. Marc Émile Pierre Adolphe Tiffeneau (November 5, 1873 – May 20, 1945)
was a French chemist who co-discovered the Tiffeneau-Demjanov
rearrangement. In 1899 he graduated from the École de pharmacie de Paris, and
afterwards began work as a pharmacy intern in Paris hospitals. In 1904 he was
named chief pharmacist at the Hôpital Boucicaut, and from 1927, worked in a
similar capacity at the Hôtel-Dieu de Paris. From 1926 to 1944 he was a
professor of pharmacology to the faculty of medicine at the Sorbonne
Nikolay Yakovlevich Demyanov (Russian: Никола́й Я́ковлевич
Демья́нов; March 27 [O.S. March 15] 1861, Tver – March 19,
1938, Moscow), also known as Demjanov and Demjanow, was a
Russian organic chemist and a member of the USSR Academy of
Sciences (1929). He is internationally known for the Demjanov
rearrangement organic reaction and other discoveries.
Tiffeneau–Demjanov rearrangement

3. The Tiffeneau–Demjanov rearrangement (TDR) is the chemical
reaction of a 1-aminomethyl-cycloalkanol with nitrous acid to form
an enlarged cycloketone.
The Tiffeneau–Demjanov ring expansion, Tiffeneau–Demjanov
rearrangement, or TDR, provides an easy way to increase amino-
substituted cycloalkanes and cycloalkanols in size by one carbon.
Ring sizes from cyclopropane through cyclooctane are able to
undergo Tiffeneau–Demjanov ring expansion with some degree of
success.
Yields decrease as initial ring size increases, and the ideal use of
TDR is for synthesis of five, six, and seven membered rings.
A principal synthetic application of Tiffeneau–Demjanov ring
expansion is to bicyclic or polycyclic systems.

4. Carbocation 1,2-rearrangement of beta-aminoalcohols on treatment
with
nitrous acid via diazotization to afford carbonyl compound through C-
C
bond migration.
A specific variant of this reaction which leads to one
carbon ring expansion is known as the Tiffeneau-Demjannov
rearrangement and it is very useful for homologation of cyclic ketones
by
the use of nitromethane or diazomethane. This reaction is applicable
to
those cyclic ketones which contain three to seven carbons in the ring
of
the substrate.

5. Homologation of cyclic ketone with
diazomethane

6. Mechanism:
The mechanism of both the Demjanov and Tiffeneau-Demjanov
rearrangements is essentially the same. The first
step is the formation of the nitrosonium ion or its precursor (N2O3) from
nitrous acid. This electrophile is attacked by
the primary amino group and in a series of proton transfers the diazonium ion
is formed. This diazonium ion is very
labile due to the lack of stabilization and it readily undergoes a [1,2]-alkyl shift
accompanied by the loss of nitrogen.
The rearrangement is competitive with the substitution of the diazonium
leaving group by the solvent (e.g., water) or
with the formation of carbocations that may undergo other rearrangements
(e.g., hydride shift). The ring expansion is
favored in the Demjanov rearrangement, since the entropy of activation for
hydride shift is higher.

7. The ring enlargement of aminomethylcycloalkanes upon treatment with nitrous acid
(HNO2) to the corresponding homologous cycloalkanols is called the Demjanov
rearrangement.
This name is also given to the rearrangement of acyclic primary amines with nitrous
acid. The first rearrangement of this type was observed and reported in the early
1900s.1 Synthetically, the Demjanov rearrangement is best applied for the
preparation of five-, six-, and seven membered rings, but it is not well-suited for the
preparation of smaller or larger rings due to low yields. In 1937.
Tiffeneau observed that the treatment of 1-aminomethyl cycloalkanols (β-
aminoalcohols) with nitrous acid led to the formation of the ring-enlarged homolog
ketones.
This transformation can be regarded as a variant of the pinacol rearrangement
(semipinacol rearrangement) and is known as the Tiffeneau-Demjanov
rearrangement. This
transformation can be carried out on four- to eight-membered rings, and the yields
of the ring-enlarged products are always better than for the Demjanov
rearrangement. However, the yields tend to decrease with increasing ring size.8,9,6
If the aminomethyl carbon atom is substituted, the Demjanov rearrangement is
significantly retarded and mostly unrearranged alcohols are formed, but the
Tiffeneau-Demjanov rearrangement readily occurs. Substrates with substitution on
the ring carbon atom to which the aminomethyl group is attached undergo facile
Demjanov rearrangement.

9. 2) Demjanov Rearrangement
When 1,2-migration is initiated through formation of carbocation by
diazotisation of a primary amine is termed as Demjanov
rearrangement.

11. Ambiguity in determining the initial site of carbocation formation
presented a problem in the analysis of many pinacol rearrangements.
This uncertainty can be removed by nitrous acid deamination of the
corresponding 1º-aminoalcohols, as shown in the following equation.
Since this reaction is normally carried out under very mild conditions, the
possibility that subsequent transformations may obscure the initial
rearrangement is reduced considerably.

15. Problems 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 uses 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.
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.
Variations Tiffeneau-Demjanov rearrangement
The Tiffeneau-Demjanov rearrangement (after Marc Tiffeneau and Nikolai
Demjanov) is a variation of the Demjanov rearrangement, which involves both a
ring expansion and the production of a ketone by using sodium nitrite and
hydrogen cation. Using the TiffeneauDemjanov 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.

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