N,N-di(4-halophenyl)nitrenium ions: Nucleophilic trapping, aromatic substitution, and hydrogen atom transfer

Article abstract of DOI:10.1021/jo062578i

(Figure Presented) The reactive intermediates N,N-di(4-chlorophenyl) nitrenium ion and N,N-di(4-bromophenyl)nitrenium ion were generated through photolysis of the corresponding N-amino(2,4,6,-collidinium) ions. The behavior of these diarylnitrenium ions was characterized by laser flash photolysis, analysis of the stable photoproducts, and ab initio calculations with density functional theory. The latter predict these species to have singlet ground states. The halogenated diarylnitrenium ions are significantly longer lived than the unsubstituted diphenylnitrenium ion. Specifically, cyclization to form carbazole derivatives occurs negligibly, if at all, with the halogenated derivatives. They do, however, carry out most of the characteristic reactions of singlet arylnitrenium ions, including combining with nucleophiles on the aryl rings, adding to arenes, and accepting electrons from readily oxidized traps. Interestingly these species also abstract H atoms from 1,4-cyclohexadiene and various phenol derivatives. The implication of the latter process in relation to the computed singlet-triplet energy gaps of ca. -12.5 kcal/mol is discussed.

Full text of DOI:10.1021/jo062578i

N,N-Di(4-halophenyl)nitrenium Ions: Nucleophilic Trapping,
Aromatic Substitution, and Hydrogen Atom Transfer
Selina I. Thomas and Daniel E. Falvey*
Department of Chemistry and Biochemistry, UniVersity of Maryland, College Park, Maryland 20742
falVey@umd.edu
ReceiVed December 15, 2006
The reactive intermediates N,N-di(4-chlorophenyl)nitrenium ion and N,N-di(4-bromophenyl)nitrenium
ion were generated through photolysis of the corresponding N-amino(2,4,6,-collidinium) ions. The behavior
of these diarylnitrenium ions was characterized by laser flash photolysis, analysis of the stable
photoproducts, and ab initio calculations with density functional theory. The latter predict these
species to have singlet ground states. The halogenated diarylnitrenium ions are significantly longer
lived than the unsubstituted diphenylnitrenium ion. Specifically, cyclization to form carbazole derivatives
occurs negligibly, if at all, with the halogenated derivatives. They do, however, carry out most of the
characteristic reactions of singlet arylnitrenium ions, including combining with nucleophiles on the
aryl rings, adding to arenes, and accepting electrons from readily oxidized traps. Interestingly these
species also abstract H atoms from 1,4-cyclohexadiene and various phenol derivatives. The implication
of the latter process in relation to the computed singlet-triplet energy gaps of ca. -12.5 kcal/mol is
discussed.
Introduction
to be involved in the synthesis of the conducting polymer, poly-
(aniline).13,14 However, recently several investigators have begun
to explore applications of nitrenium ions to synthetically useful
cyclization reactions.15 Nitrenium ions have low-energy singlet
and triplet electronic states. The aryl derivatives are generally
ground state singlets, although it appears that appropriately
substituted arylnitrenium ions can be ground state triplets.16-23
Nitrenium ions are highly reactive intermediates that are
structurally characterized by a dicoordinate nitrogen bearing a
formal positive charge. Various substituted arylnitrenium ions
have been shown to be intermediates in DNA-damaging
reactions caused by metabolically activated amines.1-12 Other
examples of this class of reactive intermediates are proposed
* Address correspondence to this author. Fax: 301-314-9121.
(1) Miller, E. C.; Miller, J. A. Pharmacol. ReV. 1966, 18, 805.
(2) Miller, E. C.; Lotlikar, P. D.; Miller, J. A.; Butler, B. W.; Irving, C.
C.; Hill, J. T. Mol. Pharmacol. 1968, 4, 147.
(3) Miller, J. A.; Miller, E. C. Physico-Chemical Mechanisms of
Carcinogenesis. In Jerusalem Symposia on Quantum Chemistry and
Biochemistry; The Israel Academy of Sciences and Humanities: Jerusalem,
1969; Vol. 1, p 237.
(4) Poirier, L. A.; Miller, J. A.; Miller, E. C.; Sato, K. Cancer Res. 1967,
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Chem. 1996, 9, 355.
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Ramamurthy, V. S., Schanze, K., Eds.; Marcel Dekker: New York, 2000.
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10.1021/jo062578i CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/31/2007
4626
J. Org. Chem. 2007, 72, 4626-4634

N,N-Di(4-halophenyl)nitrenium Ions
FIGURE 2. Photoproducts isolated from the photolysis of 1 in the
presence of chlorides.
Results and Discussions
N-(4,4′-Dichlorodiphenyl) and N-(4,4′-Dibromodiphenyl)
Nitrenium Ions. N-(4,4′-dichlorodiphenylamino)-2,4,6-trim-
ethylpyridinium 1b and N-(4,4′-dibromodiphenylamino)-2,4,6-
-
trimethylpyridinium ion 1c (BF4 salts) are the two N-ami-
nopyridinium salts used in our work to generate the nitrenium
ions of interest. Upon photolysis, the N-N bond is cleaved
heterolytically to generate the nitrenium ion (Scheme 1).
The halogenated diarylpyridinium salts, 1b and 1c, were
synthesized by adapting a previously described route. The
respective hydrazines are combined with substoichiometric
amounts of 2,4,6-trimethylpyrylium tetrafluoroborate to yield
the corresponding 1b and 1c. The hydrazines are synthesized
via nitrosation of the halogenated diphenylamines followed by
reduction with zinc. Dichlorodiphenyl amine was synthesized
by using the Goldberg procedure and the bromination of
diphenylamine is accomplished by refluxing the N-benzoyl-
diphenylamine with Br2 in CH2Cl2.27-29
Laser flash photolysis was used to characterize the spectra
and lifetimes of nitrenium ions, 2b and 2c. Pulsed laser (355
nm,25 mJ, 6 ns) photolysis of 1b and 1c in CH3CN (N2 purged)
generates two strong transient absorption bands (1b: 440, 680
nm; 1c: 450, 690 nm), which appear immediately following
the excitation pulse and decay with first-order lifetimes of 240
(2b) and 124 µs (2c) (Figure 1). These bands are attributed to
the halogenated diarylnitrenium ions 2b and 2c (Scheme 1).
Carrying out the photolysis in CH2Cl2 or in the presence of
oxygen did not affect the transient absorption or the lifetime of
the transient species observed in Figure 1.
To verify the assignment of the absorption bands in Figure
1, calculations on the structures of 2b and 2c were carried out
with density functional theory (DFT). Specifically the geometries
of both the singlet and triplet states were optimized at the
B3LYP/6-31G(d,p) level and detailed results are presented in
the Supporting Information (Figure S1). As seen with previous
arylnitrenium ions, the triplet states are characterized by wider
central (C-N-C) bond angles (ca. 150°) compared with the
singlet states (ca. 126°).16,18,20,30 Likewise the singlets have
nearly coplanar phenyl rings (dihedral 36°) compared with the
triplets, where the rings are nearly orthogonal (dihedral ca. 98°).
Qualitatively, these geometric differences can be understood to
arise from maximization of overlap between the unfilled nitrogen
based p-orbital and the filled π-orbitals on the aryl rings in the
case of the singlet.
FIGURE 1. Transient spectra obtained upon photolysis of (A) 1b and
(B) 1c in CH3CN.
The chemical and spectroscopic behavior of diphenylnitre-
nium ion 2a was described in several earlier articles.21,24-26 This
intermediate can be generated through photolysis of 1-(N,N-
diphenylamino)-2,4,6-triphenylpyridinium ion. Several decay
pathways were characterized including the following: (1) a
coupled deprotonation/electrocyclization reaction, forming car-
bazole, (2) addition of simple nucleophiles (water alcohols,
halide ions) to the ring carbons, (3) addition of electron-rich
aromatics to the nitrogen as well as the para and ortho ring
positions, and (4) abstraction of hydride from suitable donors.
The following study was undertaken to ascertain the effects
of ring halogenation on the behavior of diarylnitrenium ions. It
is shown that these species are much more stable with respect
to the aforementioned deprotonation/electrocyclization process
and addition of the simple nucleophiles compared with Ph2N+.
The reactivity toward electron-rich arenes is found to be
undiminished. Calculations with density functional theory
(B3LYP) on the 4,4′-dihalo-derivatives predict that they are
ground state singlets. However, LFP experiments show that they
carry out a net H atom abstraction from several traps, a reaction
pathway that has been previously only associated with the triplet
state.
(18) Falvey, D. E.; Cramer, C. J. Tetrahedron Lett. 1992, 33, 1705.
(19) Chiapperino, D.; Anderson, G. B.; Robbins, R. J.; Falvey, D. E. J.
Org. Chem. 1996, 61, 3195.
(20) Sullivan, M. B.; Brown, K.; Cramer, C. J.; Truhlar, D. G. J. Am.
Chem. Soc. 1998, 120, 11778.
(21) Srivastava, S.; Ruane, P. H.; Toscano, J. P.; Sullivan, M. B.; Cramer,
C. J.; Chiapperino, D.; Reed, E. C.; Falvey, D. E. J. Am. Chem. Soc. 2000,
122, 8271.
(22) Srivastava, S.; Toscano, J. P.; Moran, R. J.; Falvey, D. E. J. Am.
Chem. Soc. 1997, 119, 11552.
Time dependent-density functional theory (TD-DFT) cal-
culations were carried out on the singlet and triplet states of
(23) Srivastava, S.; Falvey, D. E. J. Am. Chem. Soc. 1995, 117, 10186.
(24) Moran, R. J.; Falvey, D. E. J. Am. Chem. Soc. 1996, 118, 8965.
(25) McIlroy, S.; Moran, R. J.; Falvey, D. E. J. Phys. Chem. A 2000,
104, 11154.
(26) Kung, A. C.; McIlroy, S.; Falvey, D. E. J. Org. Chem. 2005, 70,
5283.
(27) Freeman, H. S.; Butler, J. R.; Freedman, L. D. J. Org. Chem. 1978,
443, 4975.
(28) Winter, A. H.; Thomas, S. I.; Kung, A. C.; Falvey, D. E. Org. Lett.
2004, 6, 4671.
(29) Moran, R. J. Ph. D. Dissertation, University of Maryland, 1997.
(30) Cramer, C. J.; Falvey, D. E. Tetrahedron Lett. 1997, 38, 1515.
J. Org. Chem, Vol. 72, No. 13, 2007 4627

Thomas and Falvey
SCHEME 1. Photolysis of Pyridinium Salt Precusor to Generate Nitrenium Ions
SCHEME 2. Nucleophilic Addition Pathway to 2
SCHEME 3. Proposed Radical Coupling Pathway Leading to 9
TABLE 1. Calculated Energy Gap and Experimental Data for 2a,
2b, and 2c
state by ca. 12.5 kcal/mol. The ∆EST values for most arylni-
trenium ions previously studied are in the range of -11 to -18
kcal/mol and all these ions have been proven to be ground state
singlets.16
absorption (nm)
nitrenium
ions
∆EST
calcd
(kcal/mol) singlet
calcd
triplet
lifetimes
τ (ms)
exptl
Stable photoproducts. Photolysis of 1b and 1c under
conditions where nucleophilic traps are present yields stable
photoproducts that are consistent with intermediate formation
of the nitrenium ions 2. For example, in the presence of chloride
ion, photolysis of 1b and 1c yields three photoproducts: ortho
adduct 4, parent amine 5, and carbazole 6 (Figure 2). Com-
pounds 4 and 5 are obtained in a 1:1 mol ratio with trace
amounts of 6. Compound 4 is obtained as a result of addition
of chloride to the ortho carbon of one of the phenyl ring as
shown in Scheme 2. Generally the positive charge in a
diarylnitrenium ion is either localized on the nitrogen or
delocalized to the ortho or para carbon of one of the phenyl
rings resulting in the addition of the nucleophile to the nitrogen
or the phenyl ring. In the case of 2b and 2c, only compound 4
is observed, N adducts or para adducts are not observed. The
absence of the para adduct could be due to the fact that the
chloride ion adds reversibly to the para carbon, whereas the
ortho addition can be followed by deprotonation to provide the
product. A similar product study conducted on 2a in the presence
of chloride yielded both para and ortho adducts. The para
2a
2b
2c
-11.2
425, 680 1.5 (CH3CN)
-12.7
-12.4
465, 637 589 (weak) 440, 680 240 (CH3CN)
8.47 (H2O)
465, 647 580 (weak) 450, 690 124 (CH3CN)
6.57 (H2O)
the two nitrenium ions in order to predict their UV-vis spectra.
The singlet states are calculated to have two strong absorption
bands in the visible region: (1) a high wavelength transition
corresponding to a transition from the nonbonding pair on the
nitrogen to the LUMO, which is a mixture of the nitrogen-based
p-orbital and corresponding π-orbitals on the aryl rings and (2)
at lower wavelengths, two π-π* transitions separated by ca. 5
nm, one allowed and one forbidden. The triplets show a single
weak transition from what are primarily aryl-based π-orbitals
to the semioccupied sp2-like orbital on nitrogen.
As seen in Table 1, the experimental data are clearly more
consistent with the predicted singlet spectra. Furthermore, the
∆EST values obtained by DFT calculations predict that the
singlet state of 2b and 2c is lower in energy than the triplet
4628 J. Org. Chem., Vol. 72, No. 13, 2007

N,N-Di(4-halophenyl)nitrenium Ions
FIGURE 3. Photoproducts obtained from the photolysis of 1 in the presence of 1,3,5-TMB.
FIGURE 5. Transient spectra of the photolysis of 1b in CH3CN with
10% H2SO4.
FIGURE 4. UV absorption spectra for the photolysis of 1b in CH2-
Cl2 with TFA.
occurs through the intramolecular cyclization of 2a. In contrast,
the halogenated derivatives photolyze to cleanly provide the
symmetric dimer 9, along with collidine.
position in 2a is not substituted; hence nucleophilic addition at
that site is possible.
The photolysis of 1b and 1c in CD3CN was carried out under
room light and followed by 1H NMR every 20-30 min. As the
photolysis progressed, the gradual depletion of the pyridinium
precursor and the growth of hydrazine derivative 9 along with
collidine is observed. Compound 9 was isolated and character-
In addition to the ortho adduct, compounds 5 and 6 are also
obtained. Even though these compounds are not the result of
the nucleophilic addition process, they are still consistent with
formation of a cationic intermediate. The formation of 5 from
2 requires the net addition of 2 electrons and a proton to the
latter. There are two mechanisms that could lead to this result.
The first would be one-electron oxidation of chloride followed
by a subsequent H atom (or electron) transfer to the resulting
aminyl radical. Another possibility is an inner-sphere electron-
transfer mechanism similar to one proposed by Novak.31 In this
pathway a halide adds to the nitrenium ion and is then displaced
by a second halide or other nucleophile, resulting in a net
2-electron reduction of the nitrenium ion. The carbazole
derivatives, 6, are interesting, but are obtained only in trace
amounts. We assume that these are derived from secondary
photolysis of 5.
Also examined were reactions of 2b and 2c with 1,3,5-TMB.
Previous studies have shown that these nucleophiles react rapidly
with diarylnitrenium ions to yield σ-adducts. Similar σ-addition
products are observed for 2b and 2c except that no para adduct
is obtained. Photolyzing 1b and 1c in the presence of 0.02 M
1,3,5-TMB in CH3CN also yields three photoproducts: N-adduct
7, ortho adduct 8, and the parent amine 5 in a 2:2.5:1 mol ratio
(Figure 3). TMB adds either to the nitrogen or the ortho carbon
of the phenyl ring.
1
ized by H NMR, 13C NMR, and MS. To form 9 from 2b or
2c, the nitrenium ion would have to abstract an electron before
dimerizing (Scheme 3). Taking into account the fact that 2b
and 2c are relatively long-lived in most solvents and that dimer
forms in the absence of any traps, we assumed that it might be
possible to observe the nitrenium ion by steady-state UV if
dimerization could be suppressed. Therefore, we investigated
the possibility of stabilizing the nitrenium ion generated by
photolysis in solvents incapable of donating electrons.
The photolysis was performed by dissolving 1b and 1c in
different solvents with acid (H2SO4 or trifluoroacetic acid
(TFA)) and photolyzing under room light. The solvents chosen
for steady state analysis are not considered to be efficient
H-atom or electron donors (CH2Cl2, nitrobenzene, and chlo-
robenzene). The UV-vis spectra taken during the course of the
photolysis in CH2Cl2 are shown in Figure 4. A sharp absorption
band with maxima at 740 nm for 1b and 750 nm for 1c develops
and is stable for up to 2 h. This signal is attributed to the radical
cation (10) of 5. Similar steady-state UV spectra are obtained
in nitrobenzene and chlorobenzene (figures are given in the
Supporting Information). More detail about the identity of 10
will be discussed later.
Reaction in the Absence of Traps. In the absence of any
traps, diphenylnitrenium ion 2a decays to yield carbazole and
a significant amount of dimeric and oligomeric products arising
from the oxidation of the parent amine. Carbazole formation
The experiment is repeated by LFP where 1b is photolyzed
in CH3CN with 10% H2SO4. Transient spectra obtained in this
manner are shown in Figure 5. Upon photolysis, the signals
corresponding to 2 cleanly decay in favor of a new long-lived
species absorbing at 720 nm, which is then attributed to 10.
(The small, quantitative discrepancy in maxima is attributed to
(31) Pelecanou, M.; Novak, M. J. Am. Chem. Soc. 1985, 107, 4499.
J. Org. Chem, Vol. 72, No. 13, 2007 4629

Thomas and Falvey
TABLE 2. Second-Order Rate Constants (knuc) for the Reaction of
2 with Nucleophiles in CH3CN
knuc (M-1 s-1
)
traps
Cl- a
H2O
MeOH
EtOH
2a
2b
2c
1.0 × 1010 b (1.06 ( 0.03) × 1010 (9.83 ( 0.60) × 109
6.1 × 105 b
5.2 × 106 b
4.9 × 106 b
(1.51 ( 0.16) × 104
(1.07 ( 0.12) × 105
(1.05 ( 0.08) × 105
(4.28 ( 0.38) × 104
(5.56 ( 0.41) × 108
(1.12 ( 0.01) × 104
(7.74 ( 0.48) × 104
(8.18 ( 0.59) × 104
(2.30 ( 0.61) × 104
(7.65 ( 0.20) × 108
2-propanol
dGMPc
a nBu4NCl is the source for Cl-. b Reference 24. c Deoxyguanosine 5′-
monophosphate disodium salt in 9:1 buffer (PO4-3, 25 mM)/CH3CN.
differences in the solvent.) On the basis of these observations
we conclude that, in the absence of efficient nucleophilic traps,
the nitrenium ion ultimately accepts an electron and dimerizes.
The radical coupling step of intermediate radical 11 can be
suppressed by protonating the latter with strong acids. Under
such circumstances, the cation radicals persist. Less clear is the
source of reducing equivalents. It would seem improbable that
solvents such as nitrobenzene or methylene chloride and/or the
acids could function in this capacity. At this point we assume
that trace impurities in these media are serving as the source of
the reducing equivalents. However, additional studies aimed at
clarifying this are planned.
FIGURE 6. Transient spectra of the photolysis of 1b in the presence
of N,N-DMA.
Kinetic Analysis: Trapping with Simple Nucleophiles.
Along with product studies, the trapping rate constants of 2b
and 2c by various nucleophiles were measured. LFP was used
to obtain the pseudo-first-order decay rate constants (kobs) of
2b and 2c in varying concentrations of a particular nucleophile
at a specific wavelength (680 or 690 nm). The kobs thus obtained
is applied to eq 1 and the quenching rates by nucleophiles are
obtained as a second-order rate constant (kq). ko is the kobs in
the absence of nucleophile and Q is the concentration of the
nucleophile.
FIGURE 7. Transient spectra from the photolysis of 1c in the presence
of 1,3,5-TMB.
ions do react with dGMP, but with rate constants that are
approximately 10-fold lower than what has been reported for
carcinogenic mono-aryl derivatives.34 No additional intermedi-
ates were detected in these experiments. The aminyl radical
generated from electron abstraction would have been detected
at 760 nm (see the Supporting Information, Figure S8). On the
other hand, the intermediates arising from direct addition to the
C-8 position, as observed by McClelland et al., would likely
have been obscured by depletion of the N-aminopyridinium
precursor.9,11 Thus we cannot make any definitive conclusions
about the detailed mechanism of this process.
Trapping with π-Nucleophiles. Transient spectra obtained
by LFP show that readily oxidized arenes, namely, N,N-
dimethylaniline (N,N-DMA), 1,4-dimethoxybenzene (1,4-DMB),
hexamethylbenzene (HMB), and 4-methylanisole (4-MA), react
with 2b and 2c via an electron-transfer process. Figure 6
illustrates the results of LFP generation of 2b and 2c in the
presence of N,N-DMA. The absorption bands of the nitrenium
ions decay rapidly in favor of two longer lived absorption
bands: a strong band at 460 nm and a weak broad signal at
760 nm. The former is readily assigned to the cation radical of
N,N-DMA on the basis of literature precedent.35 The latter is
ascribed to the neutral radical 11 arising from one-electron
reduction of the diarylnitrenium ion.
kobs ) ko + kq[Q]
(1)
Table 2 shows that 2b and 2c react with H2O and alcohols
much more slowly than 2a, whereas chloride quenches 2b and
2c at the diffusion limit. H2O and alcohols are weaker
nucleophiles than Cl- thus their reactivity toward nitrenium ions
shows a greater dependence upon the stability of the nitrenium
ion. In the reaction of 2a with CH3OH, the -OCH3 group adds
to the para position of the phenyl ring rather than the ortho
position.24 Similar addition is not possible for 2b and 2c because
the para position is blocked by the halogens, thus reducing the
reactivity.
The low reactivity of 2b and 2c toward H2O makes it possible
to characterize their lifetimes and reaction rate constants in
aqueous media. One of the more noteworthy reactions of mono-
arylnitrenium ions (e.g., 2-fluorenylnitrenium ion) is their rapid
reactions with DNA bases, specifically with guanine.6,11,32 There
is a considerable body of evidence suggesting that the geno-
toxicity of arylnitrenium ions is related to their ability to react
rapidly with DNA balanced by their ability to survive in an
aqueous medium long enough to react with DNA.11,33 This
encouraged us to examine the reactions of the diarylnitrenium
ions with 2′-deoxyguanosine monophosphate (dGMP) in aque-
ous media using LFP. As shown in Table 2, the diarylnitrenium
Verification of the assignment of the 760 nm signals to 11
was done by generating the same radicals via an independent
route. Following a general procedure described by Lustzyk et
(34) Chiapperino, D.; McIlroy, S.; Falvey, D. E. J. Am. Chem. Soc. 2002,
124, 3567.
(35) Shida, T. Electronic Absorption Spectra of Radical Ions; Elsevier:
Amsterdam, The Netherlands, 1988.
(32) Novak, M.; Lin, J. J. J. Am. Chem. Soc. 1996, 118, 1302.
(33) Davidse, P. A.; Kahley, M. J.; McClelland, R. A.; Novak, M. J.
Am. Chem. Soc. 1994, 116, 4513.
4630 J. Org. Chem., Vol. 72, No. 13, 2007

N,N-Di(4-halophenyl)nitrenium Ions
SCHEME 4. Generation of Aminyl Radicals 11 from
N-Nitrosoamine
al., LFP was carried out on 1,1′-di(4-chlorophenyl)nitrosoamine
and 1,1′-di(4-bromophenyl)nitrosoamine36 (Scheme 4). In both
cases, broad absorption bands at 760 nm are observed that are
indistinguishable from the absorptions generated from the N,N-
DMA trapping experiments.
Similar behavior is seen with 1,4-DMB, MA, and HMB.
These arenes react with 2b and 2c to produce radical intermedi-
ates. Table 3 lists these results. In these cases a sharper transient
signal at 720 nm due to the cation radical of the diarylamine
(10) results from the subsequent protonation of 11. Because
these arenes are not as basic as DMA, any protons are capable
of adding to the radical 11. The identity of the cation radical
(10) was also confirmed by independent generation; in this case
we carried out LFP of the amines 5 in the presence of the
electron acceptor, 1,4-dicyanobenzene (Scheme 5). The cation
radicals of the traps were identified by their previously
characterized absorption bands.
FIGURE 8. Transient spectra of the photolysis of 2c in the presence
of 1,3,5-TMB (11.8 mM) and pyridine (0.41 mM).
No change in the lifetime of 1b or 1c was observed upon
addition of p-xylene, 4-bromoanisole, and 4-chloroanisole. These
have oxidation potentials >1.7 V vs SCE so we conclude that
they are incapable of reducing the nitrenium ions at a measurable
rate.
FIGURE 9. Transient spectra of the photolysis of 1c in the presence
of 1,4-CHD in CH3CN.
Two arenes 1,3-DMB and 1,3,5,-TMB also react rather
rapidly with the nitrenium ions. In these cases, new intermediates
are detected, in each case showing an apparent maximum at
410 nm (Figure 7). Previously it was reported that 2a reacts
with these same arenes to provide σ-complexes37 (Scheme 6).
The latter had apparent absorption maxima near 350 nm. In the
present case the apparent maxima are at higher wavelengths.
However, it should be noted that the observed peaks occur near
the onset of absorption of the photoreactants (1). Thus photo-
bleaching due to depletion of 1 may distort the maxima from
their true values. Further support for the assignment comes from
quenching experiments. In the earlier example the σ-complexes
were shown to be deprotonated by added base (pyridine).
Likewise in the present case the lifetimes of the assigned
σ-complexes (12) are diminished when the LFP experiments
are carried out with added pyridine (0.41 mM) (Figure 8).
Trapping with Hydrogen Atom Donors. In previous studies
we have argued that H atom abstraction is a characteristic
reaction of the triplet state of arylnitrenium ions. For example,
the yields of stable products derived from H atom transfer
increase when the nitrenium ions are generated through triplet
sensitization, rather than direct photolysis. In some cases the
intermediate cation radicals have been detected. In the case of
2a, where the nitrenium ion is known to be formed in the singlet
state and that state is clearly the ground state, apparent products
of H atom transfer were attributed to hydride, rather than H
atom transfer.25
donors. As summarized in Table 4, 1,4-cyclohexadiene, cyclo-
heptatriene, and various phenol derivatives all trap these
nitrenium ions with rate constants in range of 105 to 106 M-1
s-1. More significantly examination of the transient spectra
following photolysis shows that the corresponding amine cation
radical 10 (720 nm) forms concurrently with the decay of 2.
Figure 9 illustrates a typical case. Clearly, the H atom transfer
process is the net result of these reactions. It is of course possible
that the same intermediate could be derived from a sequential
electron and proton transfer. However, in that case we would
expect the rate constants to depend on the oxidation potential
of the donor. (Recall that arenes with Eox > 1.7 V were
unreactive toward the same nitrenium ions.) In fact 4-cyanophe-
nol (Eox ) 2.5 V) reacts with a rate constant that is only slightly
diminished relative to that of phenol (Eox ) 2.1 V). A kinetic
isotope effect study provides further evidence favoring direct
H atom transfer rather than electron transfer. Specifically we
compared the quenching of both 2b and 2c with phenol (OH)
and phenol (OD) with use of LFP. These experiments provide
a kH/kD ) 1.32.
To determine the stable products formed in these reactions,
a CD3CN solution of 1c (1 mM) was photolyzed in the presence
of 12 mM CHD. Analysis of the photolysis mixture by 1H NMR
showed clean formation of the amine 5c along with collidine,
benzene, and unreacted CHD. No other products were observed.
The apparent H atom abstraction by nitrenium ions 2b and
2c is somewhat unexpected. We are unaware of any examples
of singlet state hypovalent intermediates (carbenes, nitrenes, etc.)
abstracting H atoms to provide (cage-escaped) radical interme-
diates. The prevailing view is that singlet geminate radical pairs
generated in such reactions subsequently form bonds in prefer-
ence to escaping the solvent cage. The DFT calculations, which
Similar H atom trapping experiments were carried out wherein
2b and 2c were generated in the presence of various H atom
(36) Wagner, B. D.; Ruel, G.; Lusztyk, J. J. Am. Chem. Soc. 1996, 118,
13.
(37) McIlroy, S.; Falvey, D. E. J. Am. Chem. Soc. 2001, 123, 11329.
J. Org. Chem, Vol. 72, No. 13, 2007 4631

Thomas and Falvey
SCHEME 5. Generation of Cation Radicals 11
SCHEME 6. Addition of 2 to 1,3,5-TMB via a σ-Complex 12
TABLE 3. Second-Order Rate Constants (knuc) for the Reaction of 2 with Electron Donors in CH3CN
2b
2c
Eox
(V vs SCE)
knuc
intermediates upon
quenching (nm)
knuc
intermediates upon
quenching (nm)
traps
N,N-DMA
(M-1 s-1
)
(M-1 s-1
)
0.53
1.34
1.62
1.64
1.78
2.00
2.01
1.49
1.49
(5.06 ( 0.20) × 109
(2.45 ( 0.14) × 107
(8.08 ( 0.40) × 106
(3.14 ( 0.40) × 105
no trapping
760 (11)
720 (10)
720 (10)
720 (10)
(6.01 ( 0.40) × 109
(4.03 ( 0.23) × 107
(7.46 ( 0.12) × 106
(2.45 ( 0.11) × 105
no trapping
760 (11)
730 (10)
730 (10)
730 (10)
1,4-DMB
hexamethylbenzene
4-methylanisole
4-bromoanisole
4-chloroanisole
p-xylene
no trapping
no trapping
no trapping
no trapping
1,3-DMB
1,3,5-TMB
(2.45 ( 0.08) × 108
(1.34 ( 0.09) × 109
410 (σ-adduct)
420 (σ-adduct)
(4.21 ( 0.75) × 108
(5.17 ( 0.24) × 109
410 (σ-adduct)
420 (σ-adduct)
TABLE 4. Second-Order Rate Constants (knuc) for the Reaction of 2 with Hydrogen Atom Donors in CH3CN
kq (M-1 s-1
)
BDE
trap
Eox (V)
(kcal/mol)
2a
2b
2c
1,4-cyclohexadiene
cycloheptatriene
phenol
4-bromophenol
4-cyanophenol
1.74
1.43
2.10
2.18
2.57
76.6 ( 1.2
76.6 ( 3
90.4 ( 1
90.7
(6.5 ( 0.2) × 106
(5.86 ( 0.31) × 106
(5.65 ( 0.14) × 106
(6.81 ( 0.22) × 105
(3.76 ( 0.33) × 105
(3.31 ( 0.89) × 105
(5.13 ( 0.15) × 106
(5.99 ( 0.67) × 106
(6.46 ( 0.95) × 105
(4.73 ( 0.37) × 105
(4.89 ( 0.87) × 105
(1.4 ( 0.1) × 107
94.2
are validated by successful TD-DFT predictions of the UV-
vis spectra, show that 2b and 2c are ground state singlets with
substantial energy gaps. The LFP detection of the singlet
nitrenium ions prior to formation of the radical cations militate
against H atom abstraction by a higher energy unequilibrated
triplet state generated in the photolysis. This leaves three
possible explanations. First, it is possible that the DFT method
systematically overestimates ∆Est. Assuming diffusion-limited
H atom abstraction by the triplet and a rapid singlet-triplet
equilibrium, the rate constants in Table 1 would be consistent
with ∆Est ) 4-6 kcal/mol, which is ca. 6-8 kcal/mol lower
than the computed values (Scheme 7). Alternatively, H atom
transfer could be occurring via the singlet state through state
mixing in the transition state. An analogous mechanism has been
previously invoked to rationalize the reaction of ground-state
triplet diarylcarbenes with methanol (a singlet state trap).38,39
A state-mixing reaction pathway might demonstrate a heavy
atom effect. In our case this would be manifested in higher H
atom abstraction rate constants for the bromo derivative than
the chloro derivative. Indeed, for 4 of the 5 traps examined the
bromo derivative (2c) is found to be slightly more reactive than
the chloro derivative. However, given its small magnitude, we
consider this effect to be suggestive, rather than conclusive,
evidence for the state mixing mechanism. Finally we note that
the DFT methods employed here assume that the lowest singlet
state has a closed shell (n2) configuration. This is generally true
for most carbenes as well as for NH2+. However, it has been
demonstrated that the lowest singlet state of phenylnitrene
actually has an open shell (n,p) configuration.40,41 Thus, it is
conceivable that H atom transfer might be occurring to an open
shell singlet state diarylnitrenium ion. A more detailed examina-
(39) Rak, S. F.; Lapin, S. C.; Falvey, D. E.; Schuster, G. B. J. Am. Chem.
Soc. 1987, 109, 5003-5008.
(40) Gritsan, N. P.; Zhu, Z.; Hadad, C. M.; Platz, M. S. J. Am. Chem.
Soc. 1999, 121, 1202-1207.
(38) Griller, D.; Nazran, A. S.; Scaiano, J. C. J. Am. Chem. Soc. 1984,
106, 198-202.
(41) Hrovat, D. A.; Waali, E. E.; Borden, W. T. J. Am. Chem. Soc. 1992,
114, 8698-8699.
4632 J. Org. Chem., Vol. 72, No. 13, 2007

N,N-Di(4-halophenyl)nitrenium Ions
SCHEME 7. Reaction of Diarylnitrenium Ions with H Atom Donors
residue. The photoproducts are isolated by preparative thin layer
chromatography (20 × 20 plates; 1000 µm silica gel) with a mobile
phase of 60:40 hexanes and ethyl acetate. Three photooproducts
tion of the H atom transfer process and the electronic structures
of the diarylnitrenium ions would be interesting.
1
were isolated and characterized by H NMR, 13C NMR, and MS
Experimental Section
(DEI+): ortho adduct 4, parent amine 5, and 3,6-dihalogenated
carbazole 6. The halogenated carbazole had been observed and
characterized previously.46-48 4b (8.4 mg): 1H NMR (400 MHz,
CD3CD) δ 7.45 (m, 1 H), 7.29 (d, J ) 8.8 Hz, 2 H), 7.17 (m, 2H),
7.08 (d, J ) 8.8 Hz, 2H), 6.58 (br, 1 H); 13C NMR (400 MHz,
CD3CN) δ 141.7, 140.2, 130.2, 130.0, 129.9, 128.5, 127.3, 125.6,
124.0, 122.0, 119.0; MS (DEI+) m/z (rel intensity) 273.0 (100),
237.0 (14), 235.0 (12), 201.0 (60), 166.0 (11), 139.0 (9), 117.5
(12), 100.0 (7), 75.0 (9), 62.0 (5), 44.2 (4). 6b (trace amounts):
1H NMR (400 MHz, CD3CD) δ 8.09 (d, J ) 2.4 Hz, 2 H), 7.49 (d,
J ) 8.8 Hz, 2H), 7.41 (dd, J ) 8.0, 2.4 Hz, 2H); 13C NMR (400
MHz, CD3CN) δ; MS (DEI+) m/z (rel intensity) 235.0 (100), 200
(40), 163.9 (22), 117.5 (20), 44.2 (25). 4c (6.8 mg): 1H NMR (400
MHz, CD3CN) δ 7.57 (d, J ) 2.4 Hz,1 H), 7.42 (d, J ) 8.8 Hz, 2
H), 7.30 (dd, J ) 8.8, 2.4 Hz, 1H), 7.13 (d, J ) 8.8 Hz, 1H), 7.03
(d, J ) 8.8 Hz, 2H), 6.59 (br, 1 H); 13C NMR (400 MHz, CD3CN)
δ 142.2, 140.6, 133.1, 133.0, 131.5, 124.4, 122.4, 119.5, 114.8,
112.5; MS (DEI+) m/z (rel intensity) 360.8 (100), 316.9 (10), 245.0
(40), 201.0 (20), 166.1 (32), 139.0 (12), 100.5 (25), 75.0 (13), 63.0
(10), 50.0 (7). 6c (trace amounts): 1H NMR (400 MHz, CD3CD)
δ 8.24 (d, J ) 2.0 Hz, 2 H), 7.53 (dd, J ) 8.8, 2.0 Hz, 2H), 7.45
(d, J ) 8.8, Hz, 2H); 13C NMR (400 MHz, CD3CN) δ MS (DEI+)
m/z (rel intensity) 324.9 (100), 322.9 (55), 280.9 (10), 245.9 (18),
244.0 (15), 163.9 (18), 82.5 (10).
Calculations. The geometry optimization and vibrational fre-
quency calculations reported in Table 1 were performed with the
Gaussian 03 suite of programs. The calculations were done with
use of the density functional theory, particularly the hybrid B3LYP
functional that is comprised of Becke’s B3 three parameter gradient-
corrected exchange functional with the LYP correlation functional
of Lee, Yang, and Parr that was originally described by Stephens
et al.42-45
LFP Experiments. LFP studies were done with use of a Nd:
YAG laser that uses harmonic generators to create an output
wavelength of 266 or 355 nm. Transient absorption signal was
obtained from the probe beam generated from a 350 W Xe arc
lamp. Transient waveforms were captured on a digital oscilloscope
with a bandwidth of 350 MHz at a rate of 1 point per 10 ns.
Samples used to generate the transient absorption spectra were
prepared in distilled CH3CN. A stock solution of the pyridinium
salt is prepared in 150 mL of distilled CH3CN with the concentration
adjusted to have an optical density between 1.5 and 2.0 at 355 nm.
The stock solution was purged with N2 for at least 15 min before
collecting data. The sample was photolyzed in a quartz cuvette. A
fresh supply of the reaction mixture into the cuvette during
experiment was attained by setting up a standard N2 purged flow
cell connecting the cuvette to the stock solution via a double-headed
needle. This setup prevented the depletion of substrate and the
accumulation of photoproducts during the experiment. Waveforms
were collected for wavelengths ranging from 360 to 800 nm at an
increment of 10 nm.
Kinetic studies were done by measuring the pseudo-first-order
decay rate of the pyridinium salt in various concentrations of a
quencher. A stock solution of the pyridinium salt is prepared in
distilled CH3CN to a concentration that has an optical density
between 1.5 and 2.0 at 355 nm. A 3.0 mL portion of the stock
solution is transferred to the quartz cuvette via a syringe. The
pseudo-first-order decay rate of the transient species at a particular
wavelength (2b: 680 nm; and 2c: 690 nm) is obtained for varying
concentrations of the quencher. At least five different concentra-
tions, ranging from 0 to 1 mM, of the quencher are measured. The
quenching rate is obtained as the slope by plotting the pseudo-
first-order decay rate as a function of the quencher concentration.
Product Analysis with Chloride. A 50 mg portion of the
pyridinium salt and 400 mg of NaCl are dissolved in 50 mL of 9:1
H2O and CH3CN. The reaction mixture is placed on the lab bench
and photolyzed under room light. After photolysis, the mixture is
neutralized with aqueous NaHCO3. The organic layer is extracted.
The aqueous layer is extracted with CH2Cl2 twice. The organic
layers are combined and dried over MgSO4. Upon filtration, the
solvent is removed under reduced pressure to yield a brown oily
Product Analysis with 1,3,5-TMB. A 50 mg portion of the
pyridinium salt and 169 mg of 1,3,5-TMB are dissolved in 50 mL
of distilled CH3CN. The reaction mixture is placed on the lab bench
and photolyzed under room light. After photolysis, the mixture is
shaken with equal amounts of deionized H2O and CH2Cl2 and
neutralized with saturated NaHCO3. The extraction and character-
ization procedures are similar to those for NaCl. Three photoprod-
1
ucts are isolated and characterized by H NMR, 13C NMR, and
MS (DEI+): N adduct 7, ortho adduct 8, and parent amine 5. 7b
(12.6 mg): 1H NMR (400 MHz, CD3CD) δ 7.14 (d, J ) 9.2 Hz,
4 H), 6.88 (d, J ) 8.8 Hz, 4 H), 6.27 (s, 2H), 3.81 (s, 3H), 3.66 (s,
6H); 13C NMR (400 MHz, CD3CN) δ 162.5, 161.6, 159.4, 146.7,
129.5, 126.1, 122.1, 115.4, 92.4, 56.5, 56.1; MS (DEI+) m/z (rel
intensity) 403.0 (25), 168.0 (100), 139.0 (65), 125.0 (20), 44.0 (12).
8b (12.6 mg): 1H NMR (400 MHz, CD3CD) δ 7.19 (d, J ) 2.4
Hz, 2H), 7.13 (d, J ) 8.8 Hz, 2 H), 7.09 (m, 1H), 6.85 (d, J ) 8.8
Hz, 2H), 6.26 (s, 2H), 5.89 (br, 1H), 3.81 (s, 3H), 3.62 (s, 6H); 13
C
NMR (400 MHz, CD3CN) δ 162.6, 159.4, 144.1, 141.6, 133.2,
129.6, 129.1, 128.2, 126.1, 124.8, 121.2, 119.2, 107.4, 56.3, 56.0;
MS (DEI+) m/z (rel intensity) 403.6 (100), 344.6 (75), 337.5 (15),
203.4 (45), 183.4 (10), 42.2 (15), 28.1 (22). 7c (25.1 mg): 1H NMR
(400 MHz, CD3CD) δ 7.28 (d, J ) 9.2 Hz, 4 H), 6.83 (d, J ) 9.2
Hz, 4 H), 6.27 (s, 2H), 3.81 (s, 3H), 3.65 (s, 6H); 13C NMR (400
(46) Chmielewski, M. J.; Charon, M.; Jurczak, J. Org. Lett. 2004, 6,
3501.
(47) Derosa, M.; Quesada, P. A.; Dodsworth, D. J. J. Org. Chem. 1987,
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(48) Smith, K.; James, M. D.; Mistry, A. G.; Bye, M. R.; Faulkner, J.
D. Tetrahedron 1992, 48, 7479.
(42) Becke, A. D. Phys. ReV. A 1988, 38, 3098.
(43) Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
(44) Lee, C. T.; Yang, W. T.; Parr, R. G. Phys. ReV. B 1988, 37, 785.
(45) Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J. J.
Phys. Chem. 1994, 98, 11632.
J. Org. Chem, Vol. 72, No. 13, 2007 4633

Thomas and Falvey
MHz, CD3CN) δ 162.5, 161.6, 159.4, 147.1, 132.5, 122.5, 113.5,
92.4, 56.5, 56.1; MS (DEI+) m/z (rel intensity) 493.0 (50), 168.0
(100), 139 (53), 125 (26), 44 (25). 8c (34.5 mg): 1H NMR (400
MHz, CD3CD) δ 7.32 (dd, J ) 8.0, 2.4 Hz, 1H), 7.26 (d, J ) 8.8
Hz, 2 H), 7.23 (d, J ) 2.8 Hz, 1 H), 7.16 (d, J ) 8.4 Hz, 1H), 6.81
(d, J ) 8.8 Hz, 2 H), 6.25 (s, 2H), 5.91 (br, 1H), 3.81 (s, 3H) 3.62
(s, 6H; 13C NMR (400 MHz, CD3CN) δ 162.6, 159.4, 144.4, 141.9,
136.1, 132.5, 131.1, 129.4, 121.5, 119.7, 113.5, 112.1, 107.4, 91.9,
56.3, 55.2; MS (DEI+) m/z (rel intensity) 493.0 (100), 491.0 (80),
381 (30), 338 (15), 59 (10), 44 (20).
7.35 (d, J ) 9.2 Hz, 8H), 7.15 (d, J ) 9.2 Hz, 8H); 13C NMR (400
MHz, CD3CN) δ 142.7, 133.1, 120.1, 115.4; MS (FAB+) m/z (rel
intensity) 651.7 (6), 571.8 (4), 325.9 (17), 164 (100), 57 (14).
Steady State Analysis. A 3.0 mL portion of the pyridinium salt
dissolved in the solvent of choice is taken in a quartz cuvette. The
concentration of the reaction mixture is adjusted to have an optical
density between 1.5 and 2.0 at 355 nm. Next, 2-3 drops of acid
(H2SO4 or trifluoroacetic acid) is added to the mixture, which is
gently stirred. The sample undergoes photolysis by room light. The
UV spectrum is recorded at different time intervals as the photolysis
progresses with use of a UV/vis spectrometer. The experiment is
conducted in CH3CN, CH2Cl2, CHCl3, chlorobenzene, and ni-
trobenzene.
Product Analysis in the Absence of Trap. A 50 mg portion of
the pyridinium salt is dissolved in 50 mL of distilled CH3CN. The
reaction mixture is placed on the lab bench and photolyzed under
room light. After photolysis, the mixture is neutralized with aqueous
NaHCO3. The organic layer is extracted. The aqueous layer is
extracted with CH2Cl2 twice. The organic layers are combined and
dried over MgSO4. Upon filtration, the solvent is removed under
reduced pressure to yield a brown oily residue. The photoproducts
are isolated by preparative thin layer chromatography (20 × 20
plates; 1000 µm silica gel) with a mobile phase of 60:40 hexanes
Acknowledgment. This work was supported by the Chem-
istry Division of the National Science Foundation. Arthur Winter
assisted with some computational studies. We are also grateful
to Prof. Thomas Bally of the University of Fribourg for sharing
MOPLOT visualization software.
1
and ethyl acetate and characterized by H NMR, 13C NMR, and
Supporting Information Available: Detailed synthetic proce-
MS (DEI+). The photoproduct obtained was the hydrazine (9) and
collidine at a 1:1 mol ratio with trace amounts of parent amine (5).
The hydrazine products have been characterized previously.49-53
9b: 1H NMR (400 MHz, CD3CN) δ 7.23 (d, J ) 8.8 Hz, 8H),
7.02 (d, J ) 8.8 Hz, 8H). 9c: 1H NMR (400 MHz, CD3CN) δ
1
dures for 1b and 1c, H and 13C NMR spectra for compounds 4
and 6-9, miscellaneous LFP spectra, and Cartesian coordinates
for optimized singlet and triplet geometries of 2b and 2c. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
JO062578I
(49) Abakumov, G. A.; Razuvaev, G. A. Ser. Khim. 1966, 10, 1744.
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1019.
(52) Neugebau, F. A.; Fischer, H. Chem. Ber. 1971, 104, 886.
(53) Neugebau, F. A.; Fischer, P. H. H. Chem. Ber. 1965, 98, 844.
4634 J. Org. Chem., Vol. 72, No. 13, 2007