Understanding reactivity patterns of the dialkylaniline radical cation

Article abstract of DOI:10.1021/jo061809i

N,N-Dimethylaniline and N,N-diethylaniline react with Cu2+ to form the corresponding amine radical cations. The radical cations were characterized by their absorption spectra. In the absence of any nucleophiles, the radical cations dimerize to give tetraalkylbenzidines, and this reaction can be monitored by absorption spectroscopy, In the presence of nucleophiles such as Cl, Br, or SCN, the radical cations undergo nucleophilic substitution to give para-substituted dialkylanilines in good yields.

Full text of DOI:10.1021/jo061809i

for the generation and study of these intermediates. Radical
cations are most generally prepared by photoinduced electron
transfer (PET) in solution or electrochemical electron transfer
at an electrode surface.10-12 PET reactions generally require
elaborate experimental set up for preparing and monitoring the
follow up reactions of the generated radical cations. The short
lifetimes of the generated radical cation in certain cases make
these approaches less attractive. The electrochemical method
suffers from the disadvantage that the radical cations are formed
in very high concentrations at the electrode surface, leading to
their dimerization. This often hampers the reactions of the radical
cations with other substrates. Although long-lived radical cations
can be generated within zeolite cavities, monitoring reactions
of radical cations inside zeolites are rarely reported and often
times difficult to achieve.13
Understanding Reactivity Patterns of the
Dialkylaniline Radical Cation
Micha Kirchgessner,‡ Kesavapillai Sreenath, and
Karical R. Gopidas*
Photosciences and Photonics Group, Chemical Sciences
DiVision, Regional Research Laboratory (CSIR), TriVandrum
695 019, India
gopidaskr@rediffmail.com
ReceiVed September 1, 2006
We have recently introduced a very simple and effective
method for the generation of aromatic amine radical cations.14
The reaction involves mixing of the aromatic amine with 1 equiv
of Cu(ClO4)2 in acetonitrile solution. The amine radical cation
is generated as a result of single electron transfer from the amine
to Cu2+ as shown in eq 1.
Amine + Cu2+ f Amine+• + Cu+
(1)
We proposed that aromatic amines with oxidation potential less
than 1.0 V (vs SCE) are capable of forming radical cations by
this mechanism. In this paper, we show that this method can
be effectively explored for generating aromatic amine radical
cations and studying their reactivity patterns. Taking N,N-
dimethylaniline (DMA) and N,N-diethylaniline (DEA) as ex-
amples, we show that this reaction can be used for synthetic
applications, as well.
Addition of Cu(ClO4)2 to a solution of DMA resulted in the
disappearance of the absorption due to DMA at <300 nm and
formation of a new band at 470 nm.14 On the basis of the
literature15 and also our own experiments,14 the 470 nm band
was unambiguously assigned to the DMA radical cation
(DMA•+). The absorption at 470 nm is not very stable and
gradually decreases in intensity and changes in to a structured
absorption band (Figure 1A). This is associated with the
formation of a highly structured absorption band above 800 nm.
On the basis of the literature, this spectrum with structured
absorptions around 470 and 1000 nm is assigned to the
tetramethylbenzidine radical cation (TMB•+).16 (In a separate
experiment, this cation radical was generated by treating TMB
with 1 equiv of Cu(ClO4)2 in acetonitrile. The UV spectrum
obtained in this case was identical to that presented in Figure
1A(j).) Under the experimental conditions, TMB•+ was found
to be stable for several hours but can be decomposed upon
addition of a base such as triethylamine (TEA) or potassium
N,N-Dimethylaniline and N,N-diethylaniline react with Cu2+
to form the corresponding amine radical cations. The radical
cations were characterized by their absorption spectra. In the
absence of any nucleophiles, the radical cations dimerize to
give tetraalkylbenzidines, and this reaction can be monitored
by absorption spectroscopy. In the presence of nucleophiles
such as ClQ, BrQ, or SCNQ, the radical cations undergo
nucleophilic substitution to give para-substituted dialkyla-
nilines in good yields.
The generation and study of radical cation intermediates has
gained considerable interest in the last two decades.1-9 Although
radical cations can undergo a variety of reactions, such as bond
cleavage, ring closure, deprotonation, isomerization, nucleophilic
attack, and reactions with neutral reagents, the chemistry of
radical cations is not as well developed compared to the
chemistry of radicals or cations. Radical cations are considered
to be interesting but synthetically ineffectual intermediates. The
problem generally is associated with the techniques available
* To whom correspondence should be addressed. Fax: 91 471 2491712.
‡ Project student from Department of Chemical and Process Engineering,
University of Karlsruhe (TH), Karlsruhe, Germany.
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(16) See ref 15, page 223.
10.1021/jo061809i CCC: $33.50 © 2006 American Chemical Society
Published on Web 11/24/2006
J. Org. Chem. 2006, 71, 9849-9852
9849

in aqueous and nonaqueous solutions.18,19 In these studies,
attempts were made to detect DMA•+ using fast cyclic volta-
mmetry and optical spectrophotometry. These attempts were not
successful, and it was concluded that DMA•+ is very unstable
and undergoes dimerization by a mechanism similar to that
shown in Scheme 2. Under our experimental conditions, DMA•+
and DEA•+ were reasonably stable and could be characterized
by UV-vis spectroscopy. We also show here that the dialky-
laniline radical cation thus generated can lead to synthetically
useful reactions. Some examples are shown in Table 1. As
shown in Table 1, the radical cation produced dimerizes to give
benzidine derivatives in 83-86% yield. When a nucleophilic
reagent is present, the radical cation undergoes nucleophilic
substitution to give the para-substituted products in good yields.
See Supporting Information for experimental details and product
characterization.
Benzidine derivatives have received much interest recently
because of their applications in light-emitting diodes, field-effect
transistors, organic solar cells, and photoconductors.20-26 Oxida-
tion of dialkylanilines to radical cations and their subsequent
dimerization to benzidine derivatives has been achieved earlier
with several reagents, including Cu2+ 27-32
Jiang et al., for
.
example, reported the oxidative coupling of dialkylanilines in
62-85% yield using CuBr (1 equiv)/H2O2 (10 equiv).27 Oxida-
tive couplings using TiCl4 (1.5 equiv),28 ceric(IV)ammonium
nitrate (2 equiv),29 and organic oxidants such as 1,8-bis-
(diphenylmethylium)naphthalenediyl dication (1 equiv)30 are
recently reported. Most of these methods claim the intermediacy
of radical cations. The existence of radical cations is not proved
in any of these cases. The method presented here appears to be
better in terms of the yield, simplicity, and ease of workup
procedure. Most dialkylanilines have oxidation potentials less
than 0.9 V (vs SCE), and hence the reaction is expected to be
general for this class of compounds.
FIGURE 1. (A) Time-dependent changes observed in the absorption
spectrum of a DMA/Cu(ClO4)2 mixture. Spectra a-d were recorded at
1 min intervals, and e-j were recorded at 5 min intervals. (B) Effect
of addition of increasing amounts of TEA to solution in spectrum 1A-
(j) above.
carbonate. Figure 1B shows the disappearance of TMB•+ as a
result of TEA addition. The new band formed around 300 nm
is due to tetramethylbenzidine (confirmed by product isolation
and recording spectrum of isolated product). A solution of DEA
in acetonitrile also exhibited identical behavior as shown in
Figure 1 in the presence of 1 equiv of Cu(ClO4)2. The new
compound formed in this case was identified as tetraethylben-
zidine (TEB).
Under appropriate conditions, dialkylaniline radical cations
can be trapped using nucleophiles to give ring substitution
products in good yields as shown in Table 1. All these reactions
take place at room temperature, and special precautions, such
as inert atmosphere or dry solvents, are not required (detailed
reaction conditions, NMR, and GC-MS traces are given in the
Supporting Information). As is seen from Table 1, different types
Scheme 1 summarizes the observations made in Figure 1.
Figure 1A suggests that transformation of dialkylanilines
(PhNR2) to the tetraalkylbenzidines does not involve any stable
observable intermediates. This transformation, however, has to
involve dimerization, deprotonation, and electron donation as
shown in Scheme 2 (for DMA).
(18) Galus, Z.; White, R. M.; Rowland, F. S.; Adams, R. N. J. Am. Chem.
Soc. 1962, 84, 2065.
(19) Seo, E. T.; Nelson, R. F.; Fritsch, J. M.; Marcoux, L. S.; Leedy, D.
W.; Adams, R. N. J. Am. Chem. Soc. 1966, 88, 3498.
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67, 175.
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9, 2177.
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1992, 258, 1474.
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Prakt. Chem. 2000, 342, 58.
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(26) O’Brien, D. F.; Burrows, P. E.; Forrest, S. R.; Koene, B. E.; Loy,
D. E.; Thompson, M. E. AdV. Mater. 1998, 10, 1108.
(27) Jiang, Y.; Xi, C.; Yang, X. Synlett 2005, 1381.
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65, 3548.
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(32) Lopez-Cortes, J. G.; Penieres-Carrillo, G.; Ortega-Alfaro, M. C.;
Gutierrez-Perez, R.; Toscano, R. A.; Alvarez-Toledano, C. Can. J. Chem.
2000, 78, 1299.
Presence of a clear isosbestic point in Figure 1A suggests
that the dimerization to form the dihydrotetramethylbenzidine
dication is the slowest step in Scheme 2. In general, radical
cations and dications are highly acidic compared to neutral
molecules, and hence the second step in Scheme 2 is expected
to be very fast. The TMB thus formed is a better electron donor
(Eox ) 0.32 V vs SCE) than DMA (Eox ) 0.81 V vs SCE).17
Hence a very fast electron exchange reaction between the two
takes place, leading to the formation of the TMB cation radical.
If Cu2+ is present in excess, electron transfer from TMB to Cu2+
can also occur, leading to the formation of TMB•+.
Anodic oxidation of DMA to TMB•+ was studied previously
(17) Kavarnos, G. J.; Turro, N. J. Chem. ReV. 1986, 86, 401.
9850 J. Org. Chem., Vol. 71, No. 26, 2006

SCHEME 1
SCHEME 2
TABLE 1. Products and Yields in Cu2+-Initiated Reactions of N,N-Dialkylanilines
of nucleophiles can be used, and the limiting factor here appears
to be the solubility of the nucleophilic reagent in acetonitrile
solution.
A possible mechanism for the formation of the substitution
products is given in Scheme 3. The PhNR2•+ formed as a result
of electron transfer to Cu2+ is immediately trapped by the
nucleophile to form the radical, which gives away an electron
to form a cationic species. The electron can be transferred to
PhNR2•+ or to Cu2+ (if present in excess). The cationic species
subsequently undergoes deprotonation to give the product.
Attempts are being made to extend the scope of this reaction.
Although amine radical cations are well-known, nucleophilic
substitution reactions involving these species have attracted little
attention. Chlorination of DMA using acetyl chloride and
J. Org. Chem, Vol. 71, No. 26, 2006 9851

SCHEME 3
to generate radical cations of amines with lower oxidation
potentials. The present method of mixing the amine with Cu2+
salt seems to be much more efficient and simple.
Experimental Section
Representative Procedure for Benzidine Synthesis: Synthesis
of N,N,N′,N′-Tetramethylbenzidine. A solution of copper(II)
perchlorate hexahydrate (5.5 g, 15 mmol) in CH3CN (10 mL) was
added to a solution of N,N-dimethylaniline (1.2 g, 10 mmol) in
CH3CN (10 mL) over a period of 30 min at 25 °C, and the mixture
was stirred for 10 h. Solid K2CO3 (4.0 g) was added, and stirring
continued for 0.5 h. Filtered and the solids were washed twice with
CHCl3. The combined organic extract was washed with water and
dried over anhydrous Na2SO4. The solvent was removed, and the
residue so obtained was recrystallized from petroleum ether. Yield
of pure product was 1.0 g (83%), mp 195-196 °C (reported mp
catalyzed by ceric ammonium nitrate was reported recently,33
and this reaction might have involved DMA•+. Mechanistic
details, however, are not discussed in the paper. It is to be
mentioned that nucleophilic substitution reactions of cyanide
and methoxide ions were attempted earlier on electrolytically
generated DMA•+.34,35 Substitution of these ions, however,
occurred at the methyl group, and yields were very low.
Formation of these products was explained using a mechanism
which involved strong adsorption of the amine radical cation
on to the positive electrode. The basic reaction conditions assist
in removing a proton from the radical cation. This is followed
by loss of a second electron to the electrode to give Ph-N(CH3)-
CH2+, which undergoes reaction with cyanide or methoxide ions.
Adsorption on to the electrode and basic conditions are required
for this mechanism to operate. The amine radical cation is only
a transient intermediate in the electrolytic reaction, and the actual
species reacting with the nucleophile is a cation. The mechanism
in Scheme 3 is different from the electrolytic reactions in that
the second electron transfer and deprotonation occur after the
attack of the nucleophile.
In conclusion, we have generated radical cations of DMA
and DEA by mixing with Cu2+ in acetonitrile solution and
followed their reaction pathways using absorption spectroscopy.
We have also explored the synthetic utility of this reaction.
Oyama and co-workers have recently developed the technique
of electron transfer stopped flow (ETSF) to generate and study
the reactivity of amine radical cations.36-38 This technique
involves the use of electrochemically generated stable radical
cations, such as the tris(p-bromophenyl)amine radical cation,
1
196 °C). H NMR (CDCl3, 300 MHz): δ 7.6 (d, 4 H), 6.9 (d, 4
H), 3.1 (s, 12 H).
Representative Procedure for Substitution Reaction. Syn-
thesis of 4-Bromo-N,N-dimethylaniline. N,N-Dimethylaniline (121
mg, 1 mmol) and tetrabutylammonium bromide (640 mg, 2 mmol)
were dissolved in CH3CN (30 mL). A solution of copper(II)
perchlorate hexahydrate (740 mg, 2 mmol) in CH3CN (10 mL) was
added, and the mixture was stirred for 0.5 h at room temperature.
Solid K2CO3 (1.0 g) was added, and stirring continued for 10 min.
The reaction mixture was filtered, and the solids were washed twice
with CHCl3. The organic fractions were combined and dried over
anhydrous Na2SO4. The solvent was removed, and the residue was
taken in petroleum ether. This was filtered through a small alumina
column and crystallized from the same solvent. Yield of pure
product was 172 mg (86%), mp 54-55 °C (reported mp 55 °C).
1H NMR (CDCl3, 300 MHz): δ 7.2 (d, 2 H), 6.5 (d, 2 H), 2.9 (s,
6 H).
Acknowledgment. We thank the Council of Scientific and
Industrial Research (CSIR) and Department of Science and
Technology (DST), Government of India, for financial support.
M.K. thanks Jahrhundertstiftung and Vereinigte Studienstiftung
at University of Karlsruhe for the financial support received
for his international travel and stay at Trivandrum. K.S. thanks
CSIR, New Delhi. for the research fellowship. This is contribu-
tion number RRLT-PPG-236.
(33) Roy, S. C.; Rana, K. K.; Guin, C.; Banerjee, B. Synlett 2003, 221.
(34) Weinberg, N. L.; Reddy, T. B. J. Am. Chem. Soc. 1968, 90, 91.
(35) Andreades, S.; Zahnow, E. W. J. Am. Chem. Soc. 1969, 91, 4181.
(36) Oyama, M.; Higuchi, T.; Okazaki, S. Electrochem. Commun. 2000,
2, 675.
(37) Oyama, M.; Higuchi, T.; Okazaki, S. J. Chem. Soc., Perkin Trans.
2001, 2, 1287.
Supporting Information Available: Details of synthesis and
characterization of products. This material is available free of charge
via the Internet at http://pubs.acs.org.
(38) Goto, M.; Park, H.; Otsuka, K.; Oyama, M. J. Phys. Chem. A 2002,
106, 8103.
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