Dealkylation of Tertiary Amines
235
ϩ
Ph
N
CH3
Ph
Ph
N
CH200
Ϫ
e
Hϩ
Ph
2 ϩ 3
(oxidant)
Path d
CH3
Path c
CH3
2
O
Path a
(4)
Ph
N
CH3
N
CH2
(6)
Path e
CH3
ϩ
N
CH3
)
2 ϩ other
CH2
e)
products
Path b
H
(1)
(5)
CH3
NNDMA
CH
(7)
2
(8)
Scheme 2. Proposed mechanism for the dealkylation of NNDMA using TEAPI.
namely Fe(TPP)OAc and Fe3O(OAC)6(H2O)3Cl.[18–20] However,
better yields were obtained with the series of catalysts under the
current investigation. This shows that substitution at the b-pyrrole
positions and the ortho-phenyl position of meso-phenyl rings of
the porphyrincatalyst makes these catalysts more stable and better
catalysts towards oxidative dealkylation.
Conclusion
Based on the present observations we can conclude that we have
developed a very efficient, highly affordable, and eco-friendly
oxidant for the oxidative N-dealkylation of alkyl amines in the
presence of FeIII complexes. Though the current findings point
to an electron transfer mechanism, a hydrogen atom abstraction
cannot be ruled out in some cases.
The catalytic activity of the substituted metal complex
catalysts is higher than that of their corresponding unsubstituted
counterparts.
TEAPI facilitates oxygen transfer to the substrate, generating
mono-oxygenated amine as the main product.
Further investigation to explore new oxidants and simpler
catalysts is underway.
The selective formation of N-methylformanilide shows that
TEAPI facilitates transfer of oxygen to the substrate. Hanzlik
et al.[21] and Macdonald et al.[22] have suggested that oxidative
dealkylation of tertiary amines by cytochrome P-450-dependent
mono-oxygenase is initiated by a one-electron transfer process
from the tertiary amine to the active oxidizing species. Another
possible initial step of the dealkylation is hydrogen abstraction
of the amine by oxidant as reported in some reactions.[23] In
order to investigate the mechanism further, a typical Fe(OBP)
Cl-catalyzed reaction was carried out in the presence of 2,6-
di-tert-butyl-4-methyphenol. There was no significant effect on
the yield of product formation. This observation supports the
occurrence of a one-electron oxidation of the tertiary amine as
the initial step. A similar effect was reported for the demethyla-
tion of NNDMA catalyzed by FeCl3 and FeClO4.[24] Likewise,
in the latter reactions, the initial step involves one-electron
oxidation of the tertiary amine by the active oxidant. Based
on above mentioned facts, we can conclude that the reaction
proceeds through a one-electron transfer route rather than via a
hydrogen abstraction pathway.
Experimental
Tertiary amines, NNDMA and NNDEA, were purchased com-
mercially and purified before use.[27] Solvents acetonitrile,
benzene, and ethyl acetate were also purified before use. Other
reagents i.e.2,6-di-tert-butyl-4-methylphenol, butyl vinyl ether,
sodium periodate, and tertraethylammonium bromide were
obtained from commercial sources and used directly. TEAPI was
synthesized according to our procedure reported previously.[14]
The substituted FeIII porphyrin complexes, featuring electro-
negative substituents at the b-pyrrole position (octabromo-
terraphenylporphyrin, Fe(OBP)Cl) and O-phenyl position
[octachloro-octabromo-tetraphenylporphyrin, Fe(2,6,ClTPP)Cl
and Fe(OCOBP)Cl), were prepared using a modified literature
procedure.[28]
Mechanism
Although the mechanism is not entirely clear, the reaction can be
rationalized to proceed via a cytochrome P-450-based mecha-
nism based on the above observations,[25–26] Scheme 2. The
initial steps involve a one-electron oxidation of the tertiary
amine I to give an iminium cation radical 4 (Path a). Radical 4
can also be formed by H-atom abstraction of the substrate via
Path b, as reported in many studies.[23,25] However, this possi-
bility has been ruled out as there is no change in product
formation when the reaction is carried out in the presence of 2,6-
di-tert-butyl-4-methylphenol. The cation radical 4 loses a
proton to produce radical 5 (Path c). The radical 5 reacts with the
oxidant TEAPI (Path d), resulting in the formation of oxygen-
ated radical 6, which accounts for the formation of products
2 and 3. The formation of the dealkylated product 2 has also
been explained in a previous study[23] via an alternative path,
wherein the iminium cation radical 5 undergoes one-electron
oxidation to form cation 7. The latter reacts further to give
dealkylated product 2 (Path e). However, reaction with butyl
vinyl ether 8 did not yield any characterizable products. This
observation rules out the formation of cation 7. The proposed
mechanism is outlined in Scheme 2.
General Procedure for N-Dealkylation
In a typical procedure, 5 mmol of tertiary amine (NNDMA or
NNDEA) and 10 mmol TEAPI oxidant were added to 10 mL
acetonitrile in a round-bottom flask, fitted with a reflux con-
denser. Then, 0.01 mmol catalyst (Fe(OBP)Cl, Fe(OCOBP)Cl,
or Fe(2,6,ClTPP)Cl) was added to the reaction mixture. The
contents were refluxed at 608 for 7 h. Aliquots were withdrawn
periodically to monitor the consumption of the starting material
using pre-heated thin layer chromatography plates until reaction
was complete. The solvent was removed, and the remaining
solution was subjected to column chromalography over silica
gel. Benzene and ethyl acetate were used as eluents. In a typical
product separation method, when benzene was used at the
beginning of the process, a yellowish oily substance was first
eluted and identified as N-methylformanilide (mp 2408C).
Further elution with benzene resulted in the separation of a
yellow-brownish gum, which remained unidentified. The col-
umn was then eluted with a 90 : 10 (v/v) mixture of benzene and
Bhat, Daisy
