9
) albeit lower than that of HgCl2. Thus, the procedure using
SCHEME 1. Mechanism for the Mercury-Catalyzed
Rearrangement of Ketoximes
HgCl2 (12 mol %) as a catalyst in acetonitrile at 80 °C proved
to be optimal for the rearrangement.
Solvent effects on the transformation were studied (Table 2).
In place of acetonitrile, other solvents such as aprotic polar
solvents and nonpolar solvents did not accomplish the rear-
rangement effectively (less than 10% yield, Table 2). Probably
acetontrile helps the reaction by forming an acetonitrile complex
1
0,11
with mercury ion since this complexation is known.
To illustrate the general applicability of Beckmann rearrange-
ment catalyzed by an acetonitrile solution of HgCl2, a diverse
range of ketoximes12 were examined; the results are shown in
Table 3. A striking feature is that regardless of the electronic
properties of the substituents, all of the oximes, benzophenone
oximes (entries 1-5), propiophenone oximes (entries 6-9), and
acetophenone oximes (entries 10-19) were efficiently trans-
formed into their corresponding N-substituted amides in neutral
condition. The oximes with ortho substituents afforded their
corresponding amides with yields comparatively lower (entries
ion is coordinated to the oximino moiety of the oxime (A) and to
the lone pair electrons of acetonitrile to give complex B in the
presence of acetonitrile, which is in resonance with the oxo
mercury complex. The hydroxide group of complex B, which has
a strong leaving propensity, moves to the mercury ion to give
oxo mercury complex D. Concomitantly the anti periplanar alkyl
or aryl group, trans to the oxime oxygen, migrates to the cationic
species of the oximino nitrogen terminus to give the carbocation
of imine C. The carbocation C is solvated with acetonitrile to
give intermediate E or reacts with a hydroxide ion from oxo
mercury complex D to directly give imidol F. The acetonitrile
group of the intermediate E is substituted with the hydroxyl
ligand of mercury complex D to provide imidol form of amide
F. Amide G is produced from imidol form F by tautomerization.
In the presence of small amount of methanol in acetonitrile
the rearranged product was not obtained. A plausible reason is
that methanol inhibits the formation of the complex B by coor-
dination with the mercury ion, thus suppressing further reaction.
In summary, an acetonitrilomercury(II) complex efficiently
catalyzes the rearrangement of a variety of acyclic and cyclic
ketoximes with good to excellent yields under essentially neutral
condition.
1
1, 12, 14, 15, and 19) than those of the oximes with para
substituents or without substituents. Probably, the substituent
group at the ortho position partially hinders complexation
between the mercuric ion and the oxime moiety and/or impedes
a migration of the aryl group due to steric effect.
The unsymmetrical benzophenone oxime (4-fluorophenyl)-
phenylmethanone oxime gave a mixture of isomeric amides
N-(4-fluorophenyl)benzamide and 4-fluoro-N-phenylbenzamide
in the ratio of 0.8/1.0 (entry 2). Similarly, (4-methoxyphenyl)-
phenylmethanone oxime produced N-(4-methoxyphenyl)ben-
zamide and 4-methoxy-N-phenylbenzamide as an isomeric
mixture in the ratio of 1.0/0.7 (entry 3). In the reactions of the
unsymmetric propiophenone oximes and acetophenone oximes,
aryl groups migrated exclusively in preference to the alkyl
group. These results imply that electron-rich aryl groups have
better migrating aptitude than the alkyl group toward the
oximino nitrogen terminus and, thus, cationic species of the
oximino nitrogen terminus is involved (vide infra).
An investigation with cyclic ketoximes possessing several
ring size such as five-, six-, and seven-membered rings showed
that higher loading of the catalyst was required to transform the
cyclic ketoximes into their corresponding lactams with good to
better yield. The higher loading (30 mol %) of HgCl2 on the
reaction effected the conversion of cyclopentanone oxime, cyclo-
hexanone oxime, and 2-tert-butylcyclohexanone oxime into pip-
eridin-2-one, azepan-2-one, and 7-tert-butylazepan-2-one, re-
spectively, with excellent yields (84-92%), whereas its application
to the transformation of cycloheptanone oxime produced azocan-
Experimental Section
The procedure for the catalytic conversion of benzophenone
oxime into N-phenylbenzamide using mercury(II) chloride is
representative. To a solution of benzophenone oxime (197 mg, 1
mmol in 5 mL of acetonitrile) in a two-necked flask equipped with
a reflux condenser under a nitrogen atmosphere was added mercury-
(
8
(
II) chloride (33 mg, 0.12 mmol). After being stirred at 80 °C for
h, the reaction mixture was allowed to cool, and then acetonitrile
5 mL) was added to dissolve the solid formed. The solvent was
2
-one in relatively lower yield (48%). In the case of unsym-
stripped off, and the organic material was dissolved in dichlo-
romethane (4 × 10 mL). The combined organic layers were washed
with brine, dried over magnesium sulfate, and filtered. The filtrate
was evaporated under reduced pressure, and the residue obtained
was purified by flash column chromatography over silica gel (230-
400 mesh) with a dichloromethane-methanol (100:4) eluent system
to afford N-phenylbenzamide as a colorless solid (189 mg, 96%),
mp 162-163 °C.
metrical R-substituted cyclohexanone oxime, exclusive migra-
tion of an electron-rich R-carbon carrying an alkyl substituent
toward the imino nitrogen of the oxime occurred (entry 22).
The following mercury-catalyzed rearrangement mechanism
for the transformation of the oxime into amide is proposed on the
basis of the above preparative reactions and solvent and catalyst
effects (Scheme 1). Electrophilic mercury ion is stabilized by
10,11
forming a mercury complex with acetonitrile.
The mercury
Acknowledgment. Financial support from Korea Research
Foundation (KRF-2006-005-J02401) is gratefully acknowledged.
(10) Danil de Namor, A. F.; Chahine, S.; Kowalska, D.; Castellano, E.
E.; Piro, O. E. J. Am. Chem. Soc. 2002, 124, 12824-12836.
Supporting Information Available: Experimental details and
characterization data for all lactams and amides. This material is
available free of charge via the Internet at http://pubs.acs.org.
(
11) Sze, Y. K.; Irish, D. E. Can. J. Chem. 1975, 53 (3), 427-436.
12) All of the oxime substrates used in this investigation (entries 1-23
(
in Table 3) were quantitatively synthesized by refluxing a mixture of 1
equiv of the corresponding ketones, 2.3 equiv of hydroxylamine hydro-
chloride, and 2.5 equiv of sodium acetate trihydrate in aqueous methanol.
JO070297K
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538 J. Org. Chem., Vol. 72, No. 12, 2007