Reactions of N-methyl-N-(4-biphenylyl)nitrenium ion with electron-rich arenes: Laser flash photolysis and product studies

Article abstract of DOI:10.1021/ja011049n

An arylnitrenium ion, N-methyl-N-(4-biphenylyl)nitrenium ion, was generated through photolysis of 1-(N-methyl-N-4-biphenylyl)amino-2,4,6-trimethylpyridinium tetrafluoroborate, and its reactions with various donor-substituted arenes (e.g., 1,3,5-trimethoxybenzene, mesitylene, 1,4-dimethoxybenzene, hexamethylbenzene, etc.) were examined using product analysis and laser flash photolysis. In general, trapping of the short-lived nitrenium ion by the arenes leads to three types of products: (1) the parent amine, N-methyl-N-4-biphenylylamine; (2) an ortho-adduct, where the ring position ortho to the nitrenium ion center is bonded to the arene ring; and (3) an N-adduct, where the nitrenium ion nitrogen is bonded to the trap. Laser flash photolysis studies show that the rates of these trapping reactions vary from 10⁴ to 10⁹ M^-1 s^-1, depending on the structure of the arene trap. These trapping rate constants do not correlate with the one-electron oxidation potential of the arene, nor with the expected stability of a σ-complex derived from direct electrophilic aromatic substitution. It is argued that the observed rate constants correspond to initial formation of a π-complex between the arylnitrenium ion and the arene trap. This complex then forms the observed products.

Full text of DOI:10.1021/ja011049n

Published on Web 03/14/2002
Reactions of N-Methyl-N-(4-biphenylyl)nitrenium Ion with
Electron-Rich Arenes: Laser Flash Photolysis and Product
Studies
Dominic Chiapperino, Sean McIlroy, and Daniel E. Falvey*
Contribution from the Department of Chemistry and Biochemistry, UniVersity of Maryland,
College Park, Maryland 20742
Received April 25, 2001. Revised Manuscript Received October 11, 2001
Abstract: An arylnitrenium ion, N-methyl-N-(4-biphenylyl)nitrenium ion, was generated through photolysis
of 1-(N-methyl-N-4-biphenylyl)amino-2,4,6-trimethylpyridinium tetrafluoroborate, and its reactions with various
donor-substituted arenes (e.g., 1,3,5-trimethoxybenzene, mesitylene, 1,4-dimethoxybenzene, hexameth-
ylbenzene, etc.) were examined using product analysis and laser flash photolysis. In general, trapping of
the short-lived nitrenium ion by the arenes leads to three types of products: (1) the parent amine, N-methyl-
N-4-biphenylylamine; (2) an ortho-adduct, where the ring position ortho to the nitrenium ion center is bonded
to the arene ring; and (3) an N-adduct, where the nitrenium ion nitrogen is bonded to the trap. Laser flash
4
9
-1 -1
photolysis studies show that the rates of these trapping reactions vary from 10 to 10 M
s , depending
on the structure of the arene trap. These trapping rate constants do not correlate with the one-electron
oxidation potential of the arene, nor with the expected stability of a σ-complex derived from direct electrophilic
aromatic substitution. It is argued that the observed rate constants correspond to initial formation of a
π-complex between the arylnitrenium ion and the arene trap. This complex then forms the observed products.
Nitrenium ions are short-lived, electrophilic intermediates
Scheme 1
+
1-4
having the general structure RR′N .
Certain arylnitrenium
ions (i.e., those where one of the ligands on nitrogen is an
aromatic ring, e.g., 1 in Scheme 1) are intermediates in the
mechanism of electrophilic DNA damage caused by metaboli-
cally activated arylamines or nitroarenes.5 This proposal has
inspired an intense interest in the lifetimes and decay pathways
for various arylnitrenium ions. The most widely characterized
decay pathway for arylnitrenium ions involves addition of
-13
nucleophiles (water, alcohols, halide ions, etc.) to the ring
positions ortho and para to the nitrenium ion center.
The propensity of the arylnitrenium ions to trap such
nucleophiles on the ring is readily explained by the resonance
hybrid 1a which features delocalization of the positive charge
*
To whom correspondence should be addressed. E-mail: df37@
umail.umd.edu.
(
1) Abramovitch, R. A.; Jeyaraman, R. In Azides and Nitrenes: ReactiVity and
Utility; Scriven, E. F. V., Ed.; Academic: Orlando, FL, 1984; pp 297-
3
57.
onto the ring carbons. The importance of this structure has been
(
(
(
2) Simonova, T. P.; Nefedov, V. D.; Toropova, M. A.; Kirillov, N. F. Russ.
14-19
verified by a number of ab initio MO calculations
recently, by time-resolved IR spectroscopy.
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0,21
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1
996, 9, 355-360.
though less studied, decay route for singlet arylnitrenium ions
is the addition of electron-rich alkenes and arenes to the
4) Falvey, D. E. In Organic, Physical, and Materials Photochemistry;
Ramamurthy, V., Schanze, K. S., Eds.; Marcel Dekker: New York, 2000;
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22-27
28,29
nitrogen.
For example, Novak et al.
have documented
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9787-9788.
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9) Famulok, M.; Boche, G. Angew. Chem., Int. Ed. Engl. 1989, 28, 468-
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69.
(
(
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10) Turesky, R. J.; Lang, N. P.; Butler, M. A.; Teitel, C. H.; Kadlubar, F. F.
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Carcinogenesis 1991, 12, 1839-1845.
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Sci. U.S.A. 1992, 89, 8278-8282.
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(
10.1021/ja011049n CCC: $22.00 © 2002 American Chemical Society
J. AM. CHEM. SOC. 2002, 124, 3567-3577
9
3567

A R T I C L E S
Chiapperino et al.
addition of N,N-dimethylaniline to para-substituted phenyl
nitrenium ions. Studies from this laboratory have characterized
the addition of electron-rich alkenes to the nitrogen of the
greater kinetic discrimination in its reaction with various arenes,
allowing for a clearer picture of its selectivity. The stabilization
afforded by the 4-phenyl substituent also gives the arylnitrenium
ion a longer lifetime, allowing observation of its reactions with
less reactive traps. Finally, the photochemical precursor to this
nitrenium ion, 2 (eq 2), has a strong absorption band in the
high wavelength UV region. This allows for LFP generation of
the nitrenium ion using excitation wavelengths (355 nm) which
are not absorbed by the simple arenes employed as traps.
30
diphenylnitrenium ion. The DNA base guanine also forms a
similar adduct on the nitrogen (eq 1).6
,11,31-35
However, the
mechanism of this addition remains controversial, and it is still
unclear what factors dictate the regiochemical preferences. The
conducting polymer, polyaniline (PANI), is formed through
electrochemical and chemical oxidation of aniline. Several
groups have argued that the key step involves coupling of the
phenylnitrenium ion with aniline.3
6-38
This mechanism, too, is
controversial, and competitive trapping experiments have been
interpreted as favoring an alternative radical cation mechanism,
at least for the initial dimerization step.3
9,40
In any case, both
of these examples illustrate the need for clearer information
regarding arylnitrenium ion/arene interactions. At present, there
is little or no direct data regarding the rates of arylnitrenium
ion addition to arenes, nor is it clear how the rates of these
addition reactions are affected by substitutions on the arene.
The following describes product studies and LFP experiments
carried out on 1 with various donor-substituted arenes. LFP
experiments show that the arenes react with 1 having rate
4
10
-1 -1
constants (ktrap) that vary from 10 to 10
M
s . No
intermediates are detected following the quenching process. The
ktrap values do not correlate with either the oxidation potential
of the arenes or their equilibrium constant for protonation by
strong acid. There is, however, a good correlation with the ability
of the same arenes to form π-complexes with electron-poor
arenes. It is argued that the rate-determining step involves initial
π-complexation followed by formation of a longer-lived σ-com-
plex. The latter is the precursor to the observed stable products.
The following study was carried out with the goal of
identifying various pathways by which arylnitrenium ions react
with donor-substituted arenes. It was also of interest to determine
how the rate of such reactions responds to changes in the
structure of the arene. The particular nitrenium ion employed
in these studies is N-methyl-N-(4-biphenylyl)nitrenium ion 1.
This species was chosen for study for several reasons. First, it
has already been characterized by LFP and time-resolved IR
experiments.2 Second, the lifetimes and reaction rates of several
related arylnitrenium ions with 4-phenyl substituents have been
Results
Structures of the Stable Products. Synthesis and charac-
terization of the nitrenium ion’s precursor 2 are described
21
elsewhere. As has been demonstrated earlier, photolysis of
this compound produces both nitrenium ion 1 and 2,4,6-
trimethylpyridine through a N-N bond heterolysis (eq 2). The
latter is stable and is normally recovered in nearly quantitative
yields from the photolysis mixtures. When nitrenium ion 1 is
generated in the presence of various donor-substituted arenes
1
3,41-44
studied by LFP and competitive trapping experiments.
The
(Chart 1), stable products resulting from addition of the arene
presence of the 4-phenyl group substantially stabilizes the
nitrenium ion relative to reactions with simple nucleophiles.
Thus, it was anticipated that this nitrenium ion would exhibit a
to both the ortho-phenyl ring position and the nitrogen are
formed. The parent amine 3 is also observed, which formally
can be considered to result from addition of two electrons and
one proton to the nitrenium ion 1. Scheme 2 depicts the general
result.
Chart 2 and Table 1 report specific results from trapping with
each individual arene. A common procedure for the preparative
photolyses was used in all cases unless otherwise noted. The
solutions for photolysis were purged with nitrogen before and
during photolysis and irradiated only at wavelengths >320 nm
to ensure that none of the arenes absorb light. Photoprecursor
2, arene quencher, and small amounts of perchloric acid (9 mM)
were present in these MeCN solutions. The purpose of the latter
is to protonate the amine products so that they will not be
consumed by secondary oxidation reactions. The temperature
of solutions throughout the photolysis was maintained at 22 ((3)
(
23) Novak, M.; Martin, K. A.; Heinrich, J. L. J. Org. Chem. 1989, 54, 5430-
431.
5
(
24) Helmick, J. S.; Martin, K. A.; Heinrich, J. L.; Novak, M. J. Am. Chem.
Soc. 1991, 113, 3459-3466.
(
(
25) Helmick, J. S.; Novak, M. J. Org. Chem. 1991, 56, 2925-2927.
26) Takeuchi, H.; Adachi, T.; Nishiguchi, H.; Itou, K.; Koyama, K. J. Chem.
Soc., Perkin Trans. 1 1993, 867-880.
(
(
(
27) Takeuchi, H.; Watanabe, K. J. Phys. Org. Chem. 1998, 11, 478-484.
28) Novak, M.; Rangappa, K. S. J. Org. Chem. 1992, 57, 1285-1290.
29) Novak, M.; Rangappa, K. S.; Manitsas, R. K. J. Org. Chem. 1993, 58,
7
813-7821.
30) Moran, R. J.; Cramer, C. J.; Falvey, D. E. J. Org. Chem. 1996, 61, 3195-
199.
31) Famulok, M.; Bosold, F.; Boche, G. Angew. Chem., Int. Ed. Engl. 1989,
(
(
3
2
8, 337-338.
(32) Bosold, F.; Boche, G. Angew. Chem., Int. Ed. Engl. 1990, 29, 63-64.
(33) Novak, M.; Kennedy, S. A. J. Am. Chem. Soc. 1995, 117, 574-575.
(34) Gu, Z.; Gorin, A.; Hingerty, B. E.; Broyde, S.; Patel, D. Biochemistry 1999,
3
8, 10855-10870.
(
35) McClelland, R. A.; Ahmad, A.; Dicks, A. P.; Licence, V. J. Am. Chem.
°C using a water-jacketed quartz cell. In most cases, the adducts
Soc. 1999, 121, 3303-3310.
(
(
36) Genies, E. M.; Lapowski, M. J. Electroanal. Chem. 1987, 236, 189-197.
37) Wei, Y.; Tang, X.; Sun, Y. J. Polym. Sci., Part A: Polym. Chem. 1989,
(41) Novak, M.; Kahley, M. J.; Eiger, E.; Helmick, J. S.; Peters, H. E. J. Am.
Chem. Soc. 1993, 115, 9453-9460.
2
7, 2385-2396.
(
38) Wei, Y.; Jang, G.-W.; Chan, C. C.; Hsueh, K. F.; Hariharan, R.; Patel, S.;
Whitecar, C. K. J. Phys. Chem. 1990, 94, 7716-7721.
39) Lux, F. Polym. ReV. 1995, 35, 2915.
(42) Davidse, P. A.; Kahley, M. J.; McClelland, R. A.; Novak, M. J. Am. Chem.
Soc. 1994, 116, 4513-4514.
(
(
(43) Robbins, R. J.; Laman, D. M.; Falvey, D. E. J. Am. Chem. Soc. 1996, 118,
8127-8135.
40) Ding, Y.; Padias, A. B.; Hall, J. H. K. J. Polym. Sci., Part A: Polym.
Chem. 1999, 37, 2569-2579.
(44) Ren, D.; McClelland, R. A. Can. J. Chem. 1998, 76, 78-84.
3568 J. AM. CHEM. SOC.
9
VOL. 124, NO. 14, 2002

Studies of N-Methyl-N-(4-biphenylyl)nitrenium Ion
A R T I C L E S
Chart 1
Table 1. Product Distributions from Photolysis of 2 in the
Presence of Various Arenes
method of yield
measurement
arenea
product structurea
% yield
TMB
3
5
6
3
7
8
3
3
9
3
1
3
1
3
1
3
9
1
43
27
11
49
21
11
72
27
67
74
trace
46
trace
44
52
38
37
0.83
isolated
isolated
isolated
isolated
isolated
isolated
1,3-DMB
1
HMB
H NMR
1,4-DMB
isolated
isolated
1
1,2-DMB
H NMR
0
1
2
GC/MS
1
DUR
MES
H NMR
GC/MS
isolated
isolated
GC
GC
GC
1
,4-DMB/MESb
2
Scheme 2
a
Structure abbreviations are defined in Chart 1. b 1:5.4 ratio of 1,4-DMB
to MES.
products in sufficient quantities to allow for complete charac-
terization. Where noted, the structures are inferred from GC/
MS fragmentation patterns. In other cases, the yields of the
products were ascertained from integration of their peaks in the
1
H NMR spectrum of the crude photolysis mixture.
Chart 2
Trapping of 1 by TMB produces parent amine 3 as the major
product along with ortho-addition product 5 and N-addition
product 6 in an approximately 2:1 ratio. 1,3-DMB gives an
analogous result. Again 3 is the major product, and it is
accompanied by formation of the ortho- and N-adducts (7 and
8
, respectively) in an ca. 2:1 ratio. With 1,4-DMB, the major
product is the ortho-adduct 9 with parent amine 3 formed in
much lower yield. No N-adduct was detected with this trap,
but compound 17, derived from oxidative dimerization of 1,4-
DMB, was detected in minor (<5%) amounts. Mesitylene
(MES) behaves in a similar way: the ortho-adduct (12) yield
exceeds the yield of the parent amine (3), although the ratio is
smaller than that with 1,4-DMB.
In contrast, DUR and 1,2-DMB trap the nitrenium ion to give
parent amine 3 with only trace amounts of ortho addition
products (11 for DUR and 10 for 1,2-DMB) observed with these
two traps. Hexamethylbenzene (HMB) gives high yields of 3
along with two interesting minor products: one (15) derived
from a formal insertion of the nitrenium center into the CH
bond of the trap, and the other (16) derived from a net oxygen
insertion into the C-H bond of the trap.
To assess the relative reactivity of the arene traps, a
competition experiment was carried out. Nitrenium ion 1 was
generated in the presence of both MES (144 mM) and 1,4-DMB
(26.5 mM), and the product mixture was analyzed by GC. As
expected, we get adducts of both traps, along with the parent
amine 3. Assuming irreversible formation of the π-complex,
the ratio of addition rate constants, kDMB/kMES, can be predicted
using eq 3.
predicted
DMB
k
k
1.4Y9
[MES]
[DMB]
)
×
(3)
predicted
MES
1
.9Y12
were generated from preparative photolysis, isolated, and
characterized as pure materials. In some cases, low yields and/
or complex reaction mixtures precluded the isolation of certain
where Y9 and Y12, are the yields of products 9 and 12,
J. AM. CHEM. SOC.
9
VOL. 124, NO. 14, 2002 3569

A R T I C L E S
Chiapperino et al.
Scheme 3
Scheme 4. Electron Transfer/Radical Combination Mechanism
Table 2. 1H NMR Data for Isolated Ring Adducts
H-1 ppm
ring adducts
arene)
(coupling
constants)
(
H-2 ppm
H-3 ppm
5
8
9
1
(TMB)
6.78 (8.4 Hz)
6.83 (8.4 Hz)
6.65 (8.4 Hz)
6.75 (8.4 Hz)
6.86 (8.0 Hz)
7.61 (8.0 Hz)
7.53 (8.4, 2.3 Hz)
7.52 (8.4, 2.3 Hz)
7.51 (8.4, 2.3 Hz)
7.54 (obscured)
7.51 (8.0, 2.5 Hz)
6.76 (8.0, 2.5 Hz)
7.29 (2.3 Hz)
7.33 (2.3 Hz)
7.27 (2.3 Hz)
7.21 (2.3 Hz)
7.78 (2.5 Hz)
7.03 (2.5 Hz)
(1,3-DMB)
(1,4-DMB)
2 (MES)
a
ortho adduct
meta adduct
a
coupled doublet (H-1) in the ortho-adduct the furthest upfield.
In contrast, the model spectrum of the meta-adduct predicts the
doublet of doublets (H-2) to be the furthest upfield, and the
strongly coupled doublet, H-1, should be furthest downfield.
As is apparent from the experimental data in Table 2, the isolated
ring adducts are more consistent with the pattern predicted for
the ortho adduct. Both H-1 and H-2 show excellent quantitative
agreement with the predicted values. In the case of H-3, the
quantitative agreement is less satisfactory, the experimental
chemical shifts being consistently 0.5 ppm lower than the model
value. This can be attributed to the fact that the model
calculations assume the arene residue to be benzene, rather than
a donor-substituted aromatic ring. The H-3 proton, being nearest
to the arene substituent in both structures, would be expected
to show the largest deviation from the predicted value.
a
Predicted chemical shifts and coupling constants from literature
assuming ArdPh.
respectively and the ratio 1.4/1.9 accounts for the formation of
the common product, 3, from both trapping pathways. The
results of this experiment provide a value of 183, demonstrating
that 1,4-DMB is more reactive than MES.
One of the issues confronted in these product studies was
the assignment of the substitution pattern in the ring adducts.
The 1,3,4-trisubstituted biphenyl derivative (ortho-adduct) is the
assigned structure in all of the specific cases described below.
Theoretically, a 1,2,4-derivative, or “meta-adduct”, is plausible
as well and would be consistent with the arene adducts isolated
from DMA trapping in Novak’s work. In that study, the meta-
adducts were the major product isolated, with much smaller
yields of ortho- and N-adducts. The meta-adducts are believed
to form as the result of 1,2-aryl group migration from a para-
substituted cyclohexadienyl imine (Scheme 3).
Laser Flash Photolysis Studies: A Search for Intermedi-
ates. One of the proposed mechanisms by which nitrenium ions
could add to arenes is through an initial one-electron-transfer
reaction followed by either in-cage (geminate) or diffusive
radical-radical cation coupling. This is illustrated for the case
of TMB in Scheme 4. To the extent that the radical intermediates
escape the geminate solvent cage, it should be possible to detect
them by LFP. Previous studies have shown that the 4-biphe-
nylylaminyl radical cation has broad absorption near 646 nm.45
The radical cation arising from the putative electron-transfer
pathway in our study, 22, differs only in having an additional
methyl group on the nitrogen. The latter is not expected to have
a strong effect on the absorption maximum. To determine if
the nitrenium ion-based radical intermediates could be detected,
we generated these species by an alternative photochemical
The structural assignment of the products from this study as
ortho-adducts is based on comparison of chemical shifts for
aromatic signals in the H NMR spectra with those derived from
1
model calculations. Both the meta- and the ortho-adducts are
predicted to show three types of aromatic proton resonances:
a strongly (ortho) coupled doublet, defined as H-1, a double-
doublet, defined as H-2, and a weakly (meta) coupled doublet,
defined as H-3. Both of these structures are shown in Table 2.
The predicted chemical shifts are calculated using eq 4 in which
the effects of the various ring substituent on the chemical shift
δΗ are given by an empirically derived parameter (Z) and its
position on the benzene ring (i) relative to the observed proton.
Because of limited literature data, the arene residue was treated
as a simple phenyl ring. The model coupling constants were
assumed as 8.0 for ortho coupling and 2.5 for meta coupling.
4
6,47
pathway. Lustzyk et al.
have shown that aminyl radicals
can be generated through the photolysis of the corresponding
N-nitrosamine derivatives. These radicals are reasonably basic;
N-methylanilinyl radical (Ph(CH3)N•), for example, has a pKa
δHi ) 7.26 +
∑i Zi
(4)
(45) Shida, T. Electronic Absorption Spectra of Radical Ions; Elsevier: Am-
sterdam, 1988; p 446.
(
46) Jonsson, M.; Wayner, D. D. M.; Lusztyk, J. J. Phys. Chem. 1996, 100,
1
7539-17543.
Because of its significant shielding effect on ortho protons,
the methylamino substituent is expected to place the strongly
(47) Wagner, B. D.; Ruel, G.; Lusztyk, J. J. Am. Chem. Soc. 1996, 118, 13-
19.
3570 J. AM. CHEM. SOC.
9
VOL. 124, NO. 14, 2002

Studies of N-Methyl-N-(4-biphenylyl)nitrenium Ion
A R T I C L E S
Figure 1. Transient spectra from LFP (308 nm, 10 ns, 25-50 mJ/pulse)
of Nitrosoamine 20 at pH 8.5 (A) and pH 7.0 (B) aqueous solutions containg
1
0% CH3CN.
Scheme 5. Independent Generation of Radical 21 and Radical
Cation 22
Figure 2. Transient spectra from LFP (355 nm, 6 ns, 1-2 mJ/pulse) of 2
in CH3CN (generating nitrenium ion 1) in the presence and absence of
trapping agents: (A) no trap; (B) 29 mM TMB; (C) 57 mM HMB.
all absorb in the visible region of the spectrum, and they should
be detectable by our technique.
No additional intermediates were detected when the nitrenium
ion was generated in the presence of the various arenes. LFP
experiments were carried out where a sufficient concentration
of arene trap was added so that the lifetime of the nitrenium
ion was diminished by 80%. The transient spectrum was then
examined to determine if the radical intermediates resulting from
the electron transfer were formed. Figure 2 shows several typical
cases where nitrenium ion 1 was generated in the presence of
of 7.5. Thus, under protic conditions aminyl radicals are rapidly
converted into their cation radical conjugate acids. This is
illustrated in Scheme 5.
Using Lusztyk’s method, both the neutral aminyl radical 22
and its conjugate acid (amine cation radical, 21) were generated.
Specifically, LFP of N-nitroso-N-methyl-N-(4-biphenylyl)amine
2
0 under protic conditions (pH 7.5) generates the transient
spectrum in Figure 1B, which exhibits a maximum at 630 nm.
We assign this species to the N-methyl-N-biphenylyl radical
cation 21 on the basis of its similarity to the spectrum of its
unmethylated radical. When the experiment is repeated under
more basic conditions (pH 8.5), LFP generates the spectrum
shown in Figure 1A, where the high wavelength peak is broader
and shows a maximum at 560 nm. When 20 is photolyzed in
CH3CN containing trace amounts of water, the 560 nm peak is
detected immediately following the excitation pulse, and it is
converted into the 630 nm band showing clean isosbestic
behavior (data not shown). We assume that this is due to
protonation of the radical by adventitious water. We therefore
assign the 560 nm band to the aminyl radical 22.
29 mM TMB, 57 mM HMB, and in the absence of any trapping
agent. In each case, the only effect of the arene is to reduce the
lifetime of the nitrenium ion. No new visible absorption bands
appeared following the decay of the nitrenium ion signal. The
starting material, 2, absorbs in the region 300-400 nm, and
any new intermediate species that absorbs in this region may
be obscured by the loss of starting material. Elsewhere we will
describe similar LFP studies of N,N-diphenylnitrenium ion with
1
,4-DMB and several other electron-rich arenes. In that case,
the radical intermediates are detected in a similar LFP experi-
ment.
There are two situations where the radical intermediates could
form but escape LFP detection: (1) if the radicals couple rapidly
following their formation from electron transfer such that only
a small, undetectable, fraction exits the geminate solvent cage
(such cage lifetimes are typically regarded to be less than 1-2
ns), and (2) if the radicals form slowly, perhaps from an unstable
adduct, they might exist in a very low steady-state concentration
and elude detection. The latter case would rule out the possibility
of a direct, one-step electron transfer, but would be consistent
with radical formation by an addition/bond scission pathway.
The spectra of the cation radicals for many of the arene traps
have also been characterized either by LFP or by low-
45
temperature methods. For example, the cation radical of HMB
absorbs at 498 nm, the cation radical for 1,3-DMB has
absorption maxima at 477 and 505 nm, the cation radical of
TMB absorbs at 613 and 645 nm, and the cation radical of 1,4-
DMB absorbs at 443 and 475 nm. Thus, the intermediates
expected to arise from the proposed electron-transfer pathway
J. AM. CHEM. SOC.
9
VOL. 124, NO. 14, 2002 3571

A R T I C L E S
Chiapperino et al.
Table 3. Reaction Rate Constants (ktrap, M- s-1) for the Trapping
1
Table 4. Reaction Rate Constants (ktrap M-1 s-1) for the Trapping
of Nitrenium Ion 1 by Various Oxygen-Based Nucleophiles
of Nitrenium Ion 1 by Various Aromatic Compounds
1
k )
trap (M-1 s-1
trap
DMA
K
trap
E
ox
trap
K
trap
E
ox
nucleophiles
k
trap (M- s-1
)
nucleophiles
10
6
5
5
4
4
4
5
5
5
5
5
5
5
4
1.3 × 10
0.53 PMB (2.5 ( 0.3) × 10
1.71
1.64
1.78
2.11
2.00
water
methanol
ethanol
n-propyl alcohol
isopropyl alcohol
9.3 × 10
3.7 × 10
3.3 × 10
3.0 × 10
1.9 × 10
n-butyl alcohol
sec-butyl alcohol
tert-butyl alcohol
tetrahydrofuran
3.9 × 10
2.5 × 10
1.8 × 10
5 × 10
9
TMB
,3-DMB
HMB
(1.7 ( 0.5) × 10 1.49 4-MA (4.0 ( 0.2) × 10
8
1
(3.2 ( 0.5) × 10 1.49 DUR (3.2 ( 0.8) × 10
7
(1.2 ( 0.6) × 10 1.59 MES (9.2 ( 0.4) × 10
6
1
1
1
,4-DMB
,4-DMB-d
,2-DMB
(8.9 ( 0.6) × 10 1.34 TEB
(1.4 ( 0.2) × 10
6
3
6
(9.7 ( 0.5) × 10
TOL
(<4.0 ( 1.0) × 10 2.40
6
(6.5 ( 0.5) × 10 1.45
ability of the substituents is approximately equal, then steric
effects might determine the rate of addition. Finally, we note
that addition of the arenes increases the rate of nitrenium ion
decay, but has no noticeable effect on the initial intensity of
the nitrenium ion’s absorbance. Thus, the traps react with
nitrenium ion 1, but there is no evidence that they react with a
precursor to the nitrenium ion (e.g., the excited state of 2).
To probe for kinetic isotope effects, 1,4-DMB-d6 was
prepared wherein the methoxy groups were labeled with
deuteriums. The ktrap was measured and compared with that for
the unlabeled material. The 1,4-DMB-d6 trap shows a slightly
higher rate constant than DMB-h6, although the difference is
probably not statistically significant. In any case, it is clear that
there is no primary kinetic isotope effect on the rate of the
trapping reaction.
LFP Studies: Rate Constants for Trapping Reactions. The
rate constants for the reactions of nitrenium ion 1 with various
arenes (ktrap) were determined using LFP with the goal of
learning how changes in trap structure affect the reactivity. As
demonstrated earlier, LFP of precursor 2 generates nitrenium
ion 1, which can be detected at its λmax of 480 nm. The pseudo-
first-order decay constant (kobs) of the arylnitrenium was
determined at various concentrations of arene trap. Unless
otherwise noted, all of these rate constants conformed well to
the pseudo-first-order relationship (eq 5), where ko is the decay
rate constant in the absence of trapping agent, ktrap is the second-
order rate constant for the reaction of the nitrenium ion with
the arene, and [T] is the concentration of the arene trap. The
ktrap values for various arenes are compiled in Table 3, along
For comparison purposes, ktrap values for some oxygen-based
nucleophiles were also characterized. These nucleophiles, listed
with their rate constants in Table 4, include several simple
with the electrochemical oxidation potentials (Eox) for each arene
taken from previous studies.48,49
i
alcohols (CH3OH, PrOH, etc.) and an ether, (tetrahydrofuran).
kobs ) k + ktrap[T]
(5)
o
In the case of the alcohols, the addition mechanism has been
well established by previous work to involve complexation of
the oxygen atom to the ring carbons of the arylnitrenium
In most cases, the kinetic experiments were carried out by
adding small amounts of the trap to solutions of the photopre-
cursor 2 and by measuring the decay kinetics of 1 which were
generated by LFP. In the case of HMB, low solubility prevented
measurement in neat CH3CN, so the ktrap reported was deter-
mined in a 3:2 toluene-CH3CN solvent mixture. The ktrap for
toluene was estimated from comparison of the decay rate in
neat CH3CN to that in neat PhCH3 and considering the molar
concentration of pure toluene (8.4 M). Given the small change
in kobs and the fact that only two concentration points are used
in the determination, this particular value should be regarded
as an approximate upper limit.
1
9,50-53
ion.
In the present study, the alcohols all trap the
nitrenium ion with knuc values that fall in the remarkably narrow
5
-1 -1
range of 1.8 to 3.9 × 10 M s , suggesting that ktrap is not
particularly sensitive to the steric bulk of the nucleophile.
Discussion
Historically, the addition of electrophiles to arenes has been
studied with respect to two general pathways. One involves
initial formation of a π-complex, which involves a delocalized
interaction of the electrophile with the arene, and the other
involves a σ-complex, where the electrophile interacts specif-
The arenes react with the nitrenium ion 1 showing a wide
5
4,55
9
ically with one carbon atom.
These two intermediates are
range of rate constants. The ktrap values vary from 1.7 × 10
+
-1
-1
4
-1 -1
illustrated in Scheme 6. With simple electrophiles such as NO ,
M
s
for TMB to 9.2 × 10 M
s
for MES. Even a casual
inspection of Table 2 demonstrates that there is no correlation
2
Br2, etc., the initial step is widely regarded to be formation of
the σ-complex. The arylnitrenium ions are larger and have much
more delocalized positive charge than do the simple electrophiles
that have been classically associated with electrophilic aromatic
substitution. Therefore, there was reason to suspect that its mode
of addition may be different than these more localized electro-
philes.
of ktrap with Eox. For example, the readily oxidized substrate,
2
1
,4-DMB (Eox ) 1.34 V), traps the nitrenium ion ca. 10 times
more slowly than does TMB (Eox ) 1.49 V). Likewise, 1,2-
DMB traps the nitrenium ion ca. 50 times more slowly than
1,3-DMB, even though both traps have approximately the same
Eox. Nor is ktrap determined solely by the nature of the
substituent. For example, the alkyl derivatives and HMB and
PMB are more reactive than the alkoxy derivative 4-MA.
Finally, there is no simple correlation between the steric
demands of the arene and the rate of trapping. Thus, HMB is
more reactive than MES. Likewise, TMB is more reactive than
The rates for nitrenium ion arene reaction correlate with the
equilibrium constant for π-complexation. Figure 3 compares log-
(
50) Novak, M.; Kahley, M. J.; Lin, J.; Kennedy, S. A.; Swanegan, L. A. J.
Am. Chem. Soc. 1994, 116, 11626-11627.
(
51) Robbins, R. J.; Yang, L. L.-N.; Anderson, G. B.; Falvey, D. E. J. Am.
Chem. Soc. 1995, 117, 6544-6552.
1
,3-DMB. On the other hand, triethylbenzene (TEB) is slightly
(52) Sukhai, P.; McClelland, R. A. J. Chem. Soc., Perkin Trans. 2 1996, 1529-
1530.
less reactive than MES, suggesting that if the electron-donating
(53) Ramlall, P.; McClelland, R. A. J. Chem. Soc., Perkin Trans. 2 1999, 225-
232.
(
48) Eberson, L. Electron-Transfer Reaction in Organic Chemistry; New York,
Springer-Verlag 1987.
(54) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic
Chemistry; Harper and Row: New York, 1987.
(55) Hubig, S. M.; Kochi, J. K. J. Org. Chem. 2000, 65, 6807-6818.
(49) Rathore, R.; Kochi, J. K. AdV. Phys. Org. Chem. 2000, 35, 193-317.
3572 J. AM. CHEM. SOC.
9
VOL. 124, NO. 14, 2002

Studies of N-Methyl-N-(4-biphenylyl)nitrenium Ion
A R T I C L E S
Scheme 7. Oxygen Complexation Mechanism
Scheme 8. Hydride and H Atom Transfer
nism.19,51,58 The ktrap for methanol should represent a conserva-
tive upper limit for the rate of oxygen complexation by the
alkoxybenzenes. This is because the alkoxybenzenes are more
sterically encumbered than methanol and because aromatic rings
withdraw electron density from oxygen substituents, rendering
them far less nucleophilic than simple alcohols or alkyl ethers.
Figure 3. Relationship of trapping rate constants to the binding equilibrium
constants for trinitrobenzene.
2
1
An earlier study provides a ktrap value for methanol of 3.8 ×
Scheme 6
5
-1 -1
1
0 M s , which is slower than ktrap for any of the alkoxy-
benzene derivatives studied here. Furthermore, oxygen com-
plexation would not be consistent with the observed effects of
substitution on the rates. For example, 1,3-DMB has its two
alkoxy groups in a meta arrangement. In this orientation, they
ought to diminish each other’s nucleophilicity. However, 1,3-
DMB reacts more rapidly than does its 1,4-isomer in which the
para-disposition of the alkoxy groups would be expected to
reinforce each other’s nucleophilicity through resonance. Thus,
the oxygen complexation pathway is expected to contribute
negligibly, if at all, to the observed ktrap values.
In many cases, σ-complexes of electrophiles with benzene
derivatives are stable and can be characterized by UV-vis
(
ktrap) with log(KTNB), where KTNB is the equilibrium constant
for the same arenes forming charge-transfer complexes with the
trinitrobenzene (eq 6).56 The alkyl-substituted benzenes all show
an excellent linear free energy relationship when analyzed in
this manner. This was compared with a similar plot of log-
(
spectroscopy. For example, the σ-complex of nitronium ion
+
(
NO2 ) with HMB has a λmax at 430 nm with a molar
4
-1
-1 55
absorptivity of nearly 10 M cm . This suggests that any
σ-complexes formed directly from the reaction of the arenes
with the nitrenium ion ought to be detectable in the LFP
experiments. The fact that no new signals are detected in the
visible region following the decay of nitrenium ion can be taken
as evidence, albeit of a negative kind, that σ-complexes are not
formed immediately upon quenching of the nitrenium ion. The
absorption maxima of the proposed π-complexes could, in
principle, be predicted from the ionization potential of the arenes
ktrap) and log(KHF), where KHF is the equilibrium constant for
57
ring-protonation by a strong acid (HF, eq 7). In this case, there
is a much poorer correlation.
5
6
and the electron affinity of the nitrenium ion. Unfortunately,
the latter parameter is not known. It is possible that these
complexes absorb with insufficient intensity and/or at wave-
lengths too low (<390 nm) to be detected under our conditions.
With all of the arenes, significant yields of the parent amine
3
are observed. This sort of product has been shown to arise
from sequential H atom abstraction reactions of triplet state
This linear free energy correlation favors a mechanism
involving initial formation of a π-complex. However, only the
alkylbenzenes were used for the comparison due to limited
equilibrium data available in the literature. The possibility
remains that the alkoxy derivatives react through an alternative
mechanism. One alternative is the oxygen complexation path-
way, shown in Scheme 7, in which the nonbonding electron
pair on oxygen adds to one of the ring carbons of the nitrenium
ion’s phenyl ring. Indeed, simple alcohols add by this mecha-
59,60
nitrenium ions,
and hydride transfer to singlet state nitrenium
6
1
+
ions. For example, the parent nitrenium ion, NH2 , has been
shown to exhibit both of these behaviors (Scheme 8).62
Nitrenium ion 1 has a singlet ground state with a singlet-triplet
energy gap of -18.2 kcal/mol. This has been determined from
(
(
(
58) Novak, M.; Kahley, M. J.; Lin, J.; Kennedy, S. A.; James, T. G. J. Org.
Chem. 1995, 60, 8294-8304.
59) Anderson, G. B.; Yang, L. L.-N.; Falvey, D. E. J. Am. Chem. Soc. 1993,
115, 7254-7262.
60) Srivastava, S.; Falvey, D. E. J. Am. Chem. Soc. 1995, 117, 10186-10193.
(
56) Foster, R. Organic Charge-Transfer Complexes; Academic: New York,
(61) McIlroy, S.; Moran, R. J.; Falvey, D. E. J. Phys. Chem. A 2000, 104,
1
969.
11154-11158.
(57) Andrews, L. J.; Keefer, R. M. Molecular Complexes in Organic Chemistry;
(62) Srivastava, S.; Kercher, M.; Falvey, D. E. J. Org. Chem. 1999, 64, 5853-
Holden-Day: San Francisco, 1964.
5857.
J. AM. CHEM. SOC.
9
VOL. 124, NO. 14, 2002 3573

A R T I C L E S
Chiapperino et al.
Scheme 9
that this result is inconsistent with a significant contribution of
hydride transfer to the observed rate constant. It should be
stressed that these arguments pertain only to the observed rates
of the trapping reactions and not to the overall process. It is
clear from the structure of the product that a net hydride transfer
must occur. The discussion below will elaborate on this point.
These considerations only argue against this occurring in the
observed trapping step.
The trends in trapping rate constants and the structures of
the products can be accounted for in the π-complexation model
illustrated in Scheme 9. In this mechanism, the primary step is
the formation of a delocalized π-complex between the arene
and the arylnitrenium ion (kpi). The latter intermediate can either
dissociate (k-pi) or further collapse to form at least three
σ-complexes: one leading to the ortho-adduct, one leading to
the N-adduct, and one involving bond formation to the para-
position on the nitrenium ion (regiochemical preferences with
respect to the arene were not explicitly investigated). (In fact,
the substitution patterns on the traps generally permit only one
type of adduct). The first two σ-complexes further deprotonate
and tautomerize to give the ortho- and N-adducts. Given this
mechanism and the assumption that the reaction of the π-com-
plex is slow relative to the preequilibrium, the trapping rate
constants measured by LFP, ktrap, are related to kpi by eq 8, where
krxn represents the sum of the rate constants for the subsequent
steps leading to the products.
k k
pi rxn
ktrap
)
(8)
k-pi
DFT (BPW91/cc-pVDZ) calculations, which were in turn
validated through experimental time-resolved infrared charac-
terization of the same species.21 Moreover, the radical inter-
mediates expected from such a process have not been detected
in the LFP experiments. On the basis of this, it seems reasonable
to exclude a triplet state mechanism.
A comparison of relative trapping yields from the 1,4-DMB
and MES and the LFP-determined rate constants can provide
additional insight into the reaction mechanism. The ratio of
kDMB/kMES from the LFP experiment is 97, whereas the value
from competitive trapping is 183. This suggests that the
formation of the π-complex is reversible and that 1,4-DMB
undergoes the first irreversible steps toward adducts more
Several observations argue against a direct hydride transfer
mechanism. First, TEB, which ought to create a more stable
secondary carbocation from hydride transfer, reacts more slowly
than MES. If the rate-determining step were hydride abstraction,
one would expect the opposite result. Second, simple ethers,
such as tetrahydrofuran, are expected to be much better hydride
transfer agents than the alkoxybenzenes inasmuch as hydride
transfer from this species would generate a more substituted,
and presumably more stable, oxenium ion. Yet THF reacts more
6
3
rapidly.
The para σ-complex does not give rise to any detectable
adducts. This contrasts with results of McClelland and Novak
where substantial yields of para-adducts are seen when 4-bi-
35,42,50,64
phenylylnitrenium ion reacts with water.
Perhaps a more
relevant example is a study by Novak where the addition of
N,N-dimethylaniline to 4-biphenylylnitrenium ion was exam-
4
-1 -1
slowly than any (5 × 10 M s ) of the alkoxybenzene
derivatives. Likewise, 2-propanol, if it carried out hydride
transfer, ought to be more reactive than either THF or any of
the primary alcohols. In fact, this secondary alcohol reacts more
slowly than any of the primary alcohols (ethanol, n-butyl
alcohol) and at approximately the same rate constant as tert-
butyl alcohol, a species which cannot generate a stable oxenium
ion.
2
9
ined. In this case, one adduct results from para addition
followed by a net 1,2-shift of the phenyl ring providing a meta
adduct (Scheme 3).
It appears that several features of the present system prevent
formation of these meta-adducts. First, the trapping reactions
were carried out in an aprotic solvent with added acid, rather
than in buffered aqueous media. The meta product requires a
general base to abstract a proton from the meta position in the
cyclic intermediate to trigger the shift of the aryl ring. This
As a final test for hydride transfer, a kinetic isotope effect
experiment was carried out. Specifically, we compared the ktrap
for 1,4-DMB and for 1,4-DMB-d6, where the deuteriums were
specifically incorporated into the methoxy groups. The measured
(63) Taken alone, the discrepancy in rate ratios might be seen as evidence that
the adducts are not derived from the LFP-detected intermediates. However,
several observations argue against this. First, the previously published TRIR
study (ref 21) leaves little doubt that the LFP intermediate is nitrenium ion
1. Second, the LFP kinetic studies make clear that nitrenium ion 1 reacts
in some manner with the arenes once it is generated. Third, it is unlikely
that the adducts are formed from a precursor to nitrenium ion 1, since
addition of arene has no apparent effect on the initial intensity of the
nitrenium ion’s LFP signal.
6
-1 -1
values were (8.9 ( 0.6) × 10 M
s
for the unlabeled trap
6
-1 -1
and (9.7 ( 0.5) × 10 M
s
for the labeled trap. It is not
clear if the apparent inverse isotope effect is significant given
the experimental uncertainty, and if so what the mechanistic
consequences of such a result would be. However, it is clear
(64) McClelland, R. A. Tetrahedron 1996, 52, 6823-6858.
3574 J. AM. CHEM. SOC.
9
VOL. 124, NO. 14, 2002

Studies of N-Methyl-N-(4-biphenylyl)nitrenium Ion
A R T I C L E S
Scheme 11. Formation of Reduction Product 3 from HMB
Scheme 10
proton abstraction is likely to be much slower in the present
system. We suggest that the initial para σ-complex survives for
a much longer time period, and then decays through relatively
slow homolytic bond scission, which would create an amine
radical along with the cation radical of the trap. That such radical
intermediates are not detected in the LFP experiments can be
attributed to the relatively long lifetime of the σ-complex, which,
in turn, generates the radicals in low steady-state concentrations.
The observation of some trap dimers and other side products
characteristic of the corresponding trap cation radicals is
consistent with this. The amine radicals are ultimately trans-
formed into the parent amines through additional reduction steps.
Thus, the consequence of para addition is the eventual formation
of the reduction product 3.
Scheme 12
It is possible that the N-σ and ortho-σ complexes also undergo
an analogous homolytic reaction. This would compete with the
tautomerization and deprotonation leading to the stable adducts.
The rate of the homolytic dissociation is likely enhanced when
there is significant steric compression between the trap and the
nitrenium ion. Thus, the highly reactive HMB is seen to give
only the parent amine and no adducts. In contrast, MES, which
has a lower ktrap than HMB, gives significant amounts of the
ortho adduct. MES has the electron-donating methyl groups
optimally situated to stabilize the ortho σ-complex. This
presumably compensates for the destabilizing steric effects,
slowing homolysis and allowing for the proton shifts required
to generate the stable adducts.
and hydroxymethylpentamethylbenzene 16, would indicate that
the additional electron (or H atom) is derived from a subsequent
electron or H atom transfer from the arene radical cation.
Because the initial radical pair forms from a singlet σ-adduct,
the resulting radical-radical ion pair must be initially formed
in the singlet state. This would make the secondary H atom
transfer or electron transfer fast relative to cage escape and
would also reduce the yield of observable radicals in the LFP
experiment. This mechanism is diagrammed in Scheme 11 for
the case of HMB. H atom transfer from the cation radical of
HMB to the amine radical 14 gives 3 and the HMB cation 18.
This pair can undergo a further coupling to produce adduct 15,
or the cation can react with adventitious water to yield 15.
An alternative route to the parent amine 3 is illustrated by
the formation of the 1,4-DMB dimer 17. Previous studies have
shown that this product forms from the coupling of two 1,4-
1
,2-DMB, whose σ-adducts are stabilized by only one para
methoxy group, but destabilized by a meta methoxy group, gives
mostly the parent amine with only traces of an adduct detected
by GC/MS. Of course, the electronic destabilization argument
would seem to predict that the 1,4-DMB should also give low
yields of adduct and high yields of parent amine for the same
reason that 1,2-DMB does. Interestingly, this is not the case.
The 1,4-isomer actually gives predominantly the ortho-adduct.
This can be traced to the most likely orientation of the
π-complex and the relative rates for formation of the ortho
σ-adduct and the para σ-adduct. As depicted in Scheme 10, the
1
,4-DMB π-complex places the negatively polarized methoxy
groups over the para and nitrenium ion centers on 1. Steric
repulsion disfavors collapse to the para σ-complex and favors
formation of the ortho σ-complex. In contrast, 1,2-DMB forms
a π-complex which has one methoxy over the nitrenium ion
center and one over the ortho carbon. This orientation disfavors
formation of the ortho σ-adduct and shows far less steric
repulsion for formation of the para σ-adduct. It is assumed that
the latter eventually suffers homolysis and eventually leads to
the parent amine.
65,66
DMB cation radicals.
In this case, it appears that dissociation
of the 1,4-DMB σ-adduct produces 1,4-DMB cation radicals.
Under these circumstances, 3 is formed from oxidation of a
second 1,4-DMB molecule by radical 14 (Scheme 12).
The ratio of N-addition to ortho-addition, on the other hand,
does correlate with the reactivity of the arene. In fact, the only
(65) Nishinaga, A.; Hayashi, H.; Matsuura, T. Bull. Chem. Soc. Jpn. 1974, 47,
1
813-1814.
Formation of reduction product requires the addition of a
second electron. The observation of the insertion product 15,
(
66) O’Neill, P.; Steenken, S.; Schulte-Frohlinde, D. J. Phys. Chem. 1975, 79,
2773-2779.
J. AM. CHEM. SOC.
9
VOL. 124, NO. 14, 2002 3575

A R T I C L E S
Chiapperino et al.
cases where N-adducts are observed are with the most reactive
traps, TMB and 1,3-DMB, and even then, these are minor
products relative to the ortho-adduct and parent amine. This
result conforms to a trend that was first observed in the trapping
ppm, 3H at 2.53 ppm) and the 2,4,6-trimethylpyridinium moiety of
remaining 2 (6H at 2.48 ppm, 3H at 2.58 ppm). Integrations in H
1
NMR spectra also provided estimates of the yield of amine 3 and, in
some cases, various adducts. Absolute yields were calculated on the
basis of the integration of the 3.10 ppm signal of the N-methyl group
+
30
of Ph2N by electron-rich alkenes. With the least reactive
alkenes, the products resulted from addition of the alkene to
the ortho and para ring on the arylnitrenium ion. Only with the
most electron-rich alkenes were small amounts of N-adduct seen.
Thus, it appears that even for π-nucleophiles there is a kinetic
preference for addition to the ring carbons of arylnitrenium ions.
This contrasts with arylcarbenium ions which add nucleo-
philes to the exocyclic carbon atom almost exclusively. Novak
et al.50 have attributed this tendency to differences in the
aromaticity of the carbenium ions as compared with that of the
corresponding arylnitrenium ions. The arylcarbenium ion’s
phenyl ring possesses more aromatic character, which would
presumably be lost in the event of ring addition by the
+
of 3H or integrations of other peaks specified. In preparative
photolyses, stated yields of isolated photoproducts are based on mole
1
amounts of converted substrate 2 which are estimated by H NMR.
GC/MS analysis was frequently employed following workup of
concentrated CD
preparative photolyses, standard workup conditions involved the
addition of roughly equal volumes of CH Cl and aqueous NaHCO to
3
CN solutions from crude photolysis mixtures. In
2
2
3
concentrated crude photolyzate. Small samples for GC/MS analysis
were taken from organic layers following extraction with CH Cl .
2
2
Standard workup procedure for small scale photolyses involved dilution
of CD CN solution to 5.0 mL with CH Cl and the addition of 5.0 mL
of aqueous NaHCO . The two-phase system was shaken, and the CH
Cl layer was sampled for GC/MS.
Preparative Photolysis of 2 with TMB. Two separate and nearly
3
2
2
3
2
-
2
nucleophile. In contrast, the arylnitrenium ion is more accurately
identical stock solutions were prepared and photolyzed over the course
of several days. The first 50.0 mL stock solution contained 50.1 mg of
described as an iminecyclohexadienyl cation.1
6-18,20,21,67
Thus,
nucleophilic addition to the aromatic ring in this latter case does
not remove aromatic character. The regiochemical results
described herein further emphasize the unusual behavior of
guanosine as a nucleophile. This species appears to react
exclusively at the nitrenium ion’s nitrogen. The reasons for this
remain uncertain. However, it is possible that this reaction may
occur via a mechanism that differs from the simple arenes
examined here.
1
4
b, 360 mg of TMB, and 40 µL of HClO (70%) for respective
concentrations of 2.57, 42.9, and 9.3 mM. The second 50.0 mL stock
solution contained 51.1 mg of 1b, 361 mg of TMB, and 40 µL of HClO4
(70%) for respective concentrations of 2.62, 43.0, and 9.3 mM. The
slight differences in the two stock solutions were considered negligible
in affecting the resulting product distributions. Both solutions were
divided into 5.0 mL portions, and each portion was purged with N
throughout 40 min of photolysis. Photolyzed samples from both stock
solutions were combined and stored in a dark freezer until all 20 5.0
2
mL portions were photolyzed. The cumulative photolyzate was sampled
Experimental Section
1
(5.0 mL) and concentrated under reduced pressure for H NMR analysis.
LFP Experiments. Laser flash photolysis (LFP) data were collected
using either an XeCl excimer laser (308 nm) or the third harmonic
Percentage conversion was calculated to be 88.5% using the general
method described. The recombined solution was concentrated under
(355 nm) of a pulsed Continuum Surelite II-10 Nd:YAG laser (<5
reduced pressure, added to aqueous NaHCO , and extracted three times
3
mJ/pulse, 4-6 ns). During a given experiment, the pulse energy varied
by <5%. The transient behavior was monitored using a probe beam
from an Oriel CW 400 W Xe arc lamp passed through the sample
cuvette perpendicular to the excitation beam. Transient waveforms were
recorded with a LeCroy 9420 digital oscilloscope which digitizes at a
rate of one point/10 ns with a bandwidth of 350 MHz. Programs
developed in our laboratory, using MATLAB 4.2 and LabView 5.0
software, were used in processing the LFP data.
with CH Cl . CH Cl extracts were combined and dried over MgSO
4
2
2
2
2
before concentrating for column chromatography. Eluting with 15%
EtOAc/85% hexanes, fractions were concentrated individually and
analyzed by TLC. Combining appropriate fractions (some mixed
fractions not included) and concentrating under reduced pressure, the
following photoproducts were obtained: 8.9 mg of amine 3, with an
estimated additional 8 mg in fractions contaminated with TMB
1
(determined by H NMR) for total estimated yield of 17 mg of 3b
1
Samples for pulsed irradiation were prepared such that the absorbance
of substrate 2 was approximately 2.0 at 355 nm. LFP transient spectra
were based on pulsed irradiation of a single 3.0 mL sample of
pyridinium salt substrate when photolyzing at 355 nm with concentrated
solutions. Low sample depletion was confirmed by steady-state UV
spectrum measurement of the sample following the LFP data collection.
(0.093 mmol, 43%, characterized by H NMR for comparison to the
spectrum of the authentic compound); 20.9 mg of ortho ring adduct 5
1
(0.060 mmol, 27%). H NMR (400 MHz, CDCl
3
): δ 7.57 (dd, J )
8.3, 1.1 Hz, 2H), 7.53 (dd, J ) 8.4, 2.3 Hz, 1H), 7.36 (t, J ) 7.7 Hz,
2H), 7.29 (d, J ) 2.3 Hz, 1H), 7.23 (t, J ) 7.7 Hz, 1H), 6.78 (d, J )
8.4 Hz, 1H), 6.26 (s, 2H), 3.88 (s, 3H), 3.72 (s, 6H), 3.70 (br s, 1H),
These samples were purged throughout the experiment with N
2
.
2.84 (s, 3H). 13C NMR (100 MHz, CDCl
3
): δ 161.1, 159.1, 147.2,
Frequent displacement of sample solution with fresh stock solution
during data collection assured that transient spectra were not affected
by excessive depletion of substrate or accumulation of photoproducts.
Stable Products from Arene Trapping. These experiments in-
volved preparation of stock solutions containing 2, arene, or other trap,
141.6, 130.5, 129.2, 128.4, 127.0, 126.3, 125.6, 120.2, 110.0, 108.3,
91.1, 56.0, 55.4, 31.1. MS (FAB) m/z (relative intensity): 351 (24),
+
350 ([M + H] , 100), 349 (43), 335 (12), 318 (11). HRMS (FAB):
calcd for C22
3
H24NO , 350.17563; found, 350.17689. 8.0 mg of N-adduct
1
6 (0.023 mmol, 11%) H NMR (400 MHz, CDCl
3
): δ 7.53 (dd, J )
and small amounts of concentrated HClO
4
3
(70%) in CH CN solvent.
8.0, 1.1 Hz, 2H), 7.41 (d, J ) 8.7 Hz, 2H), 7.36 (t, J ) 7.5 Hz, 2H),
7.21 (t, J ) 7.5 Hz, 1H), 6.57 (d, J ) 8.7 Hz, 2H), 6.21 (s, 2H), 3.86
Solutions were purged with N , and photolyzed only above 320 nm
2
(s, 3H), 3.74 (s, 6H), 3.19 (s, 3H). 13C NMR (100 MHz, CDCl
): δ
using an appropriate cutoff filter (320 nm) and an Oriel CW 400 W
Xe arc lamp. Photolyzed solutions were concentrated under reduced
pressure and dissolved in CD CN with 1% TMS for calibration of
3
chemical shift. The percentage conversion of substrate 2 following
photolysis was calculated using appropriate peaks in the 1H NMR
spectrum of crude, concentrated photolyzate. This was accomplished
using methyl group signals of protonated 2,4,6-collidine (6H at 2.60
3
158.5, 158.4, 148.5, 141.7, 132.3, 128.6, 128.5, 127.4, 126.2, 125.6,
111.9, 91.4, 56.0, 55.4, 38.6. MS (EI) m/z (relative intensity): 350
(24), 349 (100), 334 (17), 167 (27), 152 (15). HRMS (FAB): calcd
3
for C22H24NO , 350.17563; found, 350.17509.
Preparative Photolysis of 2 with 1,3-DMB. A 50 mL stock solution
was prepared which contained 49.6 mg of 1b, 0.598 g of 1,3-DMB,
4
and 40 µL of HClO (70%) in MeCN solvent for respective concentra-
(67) Cramer, C. J.; Falvey, D. E. Tetrahedron Lett. 1997, 38, 1515-1518.
tions of 2.54, 86.6, and 9.3 mM. The stock solution was divided into
3
576 J. AM. CHEM. SOC. VOL. 124, NO. 14, 2002
9

Studies of N-Methyl-N-(4-biphenylyl)nitrenium Ion
0 5.0 mL portions, and nine of these were purged with N
A R T I C L E S
1
2
and
Hz, 1H), 4.05 (br s, 1H), 3.75 (s, 3H), 3.70 (s, 3H), 2.76 (s, 3H). 13C
photolyzed (>320 nm) for 40 min each. Recombining portions, the
3
NMR (100 MHz, CDCl ): δ 154.0, 151.1, 146.3, 141.2, 129.5, 129.3,
photolyzate was sampled (5.0 mL aliquot) and concentrated under
128.9, 128.5, 127.3, 126.3, 125.9, 124.8, 117.3, 114.1, 112.9, 110.3,
1
+
reduced pressure to obtain a crude H NMR spectrum. On the basis of
56.6, 55.7, 30.9. MS (EI) m/z (relative intensity): 319.1 (M , 100),
+
the general procedure, substrate conversion was calculated to be 90%.
273.1 (37). HRMS (EI): calcd for C21
H
21NO
2
(M ), 319.15723; found,
Recombined crude photolyzate was added to aqueous NaHCO
extracted three times with CH Cl . CH Cl extracts were combined,
dried over MgSO , and concentrated under reduced pressure for column
3
and
319.15700.
2
2
2
2
Preparative Photolysis of 2 with MES. A stock solution was
prepared which contained 40.0 mg of 2, 0.85 g of MES, and 40 µL of
4
chromatography. Eluting with 12% EtOAc/88% hexanes, fractions were
collected and analyzed by TLC. Excess 1,3-DMB was the first eluted
compound followed by the N-adduct 13, amine 3b, and the ortho ring
adduct 12. By combining appropriate fractions and removing solvent
under reduced pressure and moderate temperatures (<45 °C), these
major photoproducts were isolated: 9.4 mg of 3 (0.051 mmol, 49%,
HClO
mM, 0.142 M, and 9.3 mM. The stock solution was divided into 10
5.0 mL portions, and each was purged with N and photolyzed (>320
4
(70%) in 50 mL of MeCN, for respective concentrations of 2.05
2
nm) for 1 h. The percentage of photodecomposition of 2 as measured
1
by H NMR spectra of concentrated crude photolyzate was 96 ( 3%
in all cases. Combined samples were added to aqueous NaHCO
extracted three times with CH Cl . CH Cl extracts were combined,
dried over MgSO , and concentrated under reduced pressure for column
3
and
1
characterized by H NMR which matched spectrum of authentic
2
2
2
2
1
compound); 7.0 mg of 7 (0.022 mmol, 21%). H NMR (400 MHz,
4
CDCl
3
): δ 7.55 (dd, J ) 8.2, 1.1 Hz, 2H), 7.52 (dd, J ) 8.4, 2.3 Hz,
chromatography. Eluting with 20% EtOAc/80% hexanes, fractions were
collected and analyzed by TLC. The following photoproducts were
isolated: 7.2 mg of parent amine 3 (0.039 mmol, 44%, characterized
1
7
6
H), 7.36 (t, J ) 7.7 Hz, 2H), 7.33 (d, J ) 2.3 Hz, 1H), 7.22 (t, J )
.7 Hz, 1H), 7.18 (d, J ) 7.2 Hz, 1H), 6.83 (br d, J ) 8.4, 1H), 6.59-
.56 (m, 2H), 4.32 (br s, 1H), 3.85 (s, 3H), 3.76 (s, 3H), 2.83 (s, 3H).
1
by H NMR and matched spectrum of authentic standard); and 13.9
+
1
MS (FAB) m/z (relative intensity): 320 ([M + H] , 27), 149 (25).
mg (0.0461 mmol, 52%) of adduct 12. H NMR (400 MHz, CDCl
3
):
HRMS (FAB): calcd for C21
H
22NO
2
, 320.16504; found, 320.16407.
δ 7.57-7.53 (m, 3H), 7.36 (t, J ) 7.6 Hz, 2H), 7.20 (t, J ) 7.6 Hz,
1H), 6.98 (s, 2H), 6.75 (d, J ) 8.4 Hz, 1H), 2.80 (s, 3H), 2.34 (s, 3H),
1
7
.4 mg of 8 (0.023 mmol, 22%) H NMR (400 MHz, CDCl ): δ 7.53
3
(dd, J ) 8.1, 1.0 Hz, 2H), 7.41 (d, J ) 8.7 Hz, 2H), 7.37 (t, J ) 7.5,
2.02 (s, 6H). 13C NMR (100 MHz, CDCl
3
): δ 145.8, 141.3, 137.4,
2
8
3
H), 7.23 (t, J ) 7.5 Hz, 1H), 7.12 (d, J ) 8.5 Hz, 1H), 6.66 (d, J )
137.2, 134.6, 129.5, 128.6, 128.5, 128.0, 126.7, 126.2, 126.1, 125.9,
.7, 2H), 6.58 (d, J ) 2.7 Hz, 1H), 6.51 (dd, J ) 8.5, 2.7 Hz, 1H),
109.8, 30.7, 21.1, 20.2. MS (FAB) m/z (relative intensity): 303 (25),
1
3
+
.84 (s, 3H), 3.76 (s, 3H), 3.22 (s, 3H). C NMR (100 MHz, CDCl
3
):
302 ([M + H] , 100), 301 (74), 300 (21), 287 (11), 285 (12), 271
δ 159.1, 157.1, 149.2, 141.3, 130.0, 129.5, 129.3, 128.6, 127.4, 126.2,
(10), 255 (10). HRMS (FAB): calcd for C22H24N, 302.19089; found,
1
25.8, 112.9, 104.6, 100.2, 55.7, 55.5, 39.3. MS (EI) m/z (relative
302.18948.
+
intensity): 320 ([M + H] , 26), 319 (100), 304 (18), 167 (22). HRMS
Competitive Photolysis of 1 with 1,4-DMB and MES. A solution
was prepared which contained 30.3 mg of 2 and 30 µL of HCLO (70%)
in 30 mL of MeCN for respective concentrations of 2.56 and 11.6 mM.
To a 10 mL aliquot of this solution was added 200 µL of MES (144
mM) and 36.6 mg of 1,4-DMB (26.5 mM). The solution was purged
(
EI): calcd for C21
Preparative Photolysis of 2 with 1,4-DMB. A solution was prepared
which contained 35.0 mg of 2, 69.2 mg of 1,4-DMB, and 20 µL of
HClO (70%) in 20 mL of MeCN for respective concentrations 4.48,
5.1, and 11.6 mM. This solution was divided into two equal portions,
and each was purged with nitrogen and photolyzed for 25 min using a
20 nm cutoff filter. Recombined photolyzates were sampled for crude
H21NO
2
, 319.15723; found, 319.15857.
4
4
2
with N
355 nm (100 mJ/pulse, 10 Hz, 4-6 ns pulse length) with continuous
stirring. The photolyzate was washed with 10 mL of aqueous NaHCO
and extracted three times with CH Cl . The organic layer was dried
over MgSO , and the solvent was then removed. The residue was taken
2
and photolyzed for 30 min using a Nd:YAG laser emitting at
3
3
1
H NMR analysis. Approximately 69% (0.062 mmol) of 2 was
photodecomposed. The CD CN solution of product mixture was
recombined with photolyzate and concentrated under reduced pressure.
The residue was taken up in CH Cl and combined with aqueous
NaHCO solution, extracting twice with CH Cl . The organic layer was
dried over MgSO and concentrated for column chromatography.
2
2
3
4
up in 2 mL of MeCN for GC analysis. The final concentrations were
determined to be 4.79 mM (37.4% yield) 3, 4.91 mM (38.3% yield) 9,
and 0.106 mM (0.826% yield) 12.
2
2
3
2
2
4
Acknowledgment. This work was supported by the Chemistry
Division of the National Science Foundation.
Eluting with 15% EtOAc/85% hexanes, the following compounds were
obtained: 3.1 mg of 3 (0.017 mmol, 27%, characterized by H NMR
1
for comparison to the spectrum of the authentic compound); and 13.3
Supporting Information Available: Relationship of trapping
rate constants (ktrap) for the arenes to the equilibrium constant
for addition of HF to the same arenes (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
mg (0.0417 mmol, 67%) of 9 (with traces of DMB dimer 17 < 5%).
1
H NMR (400 MHz, CD
dd, J ) 8.4, 2.3 Hz, 1H), 7.37 (t, J ) 7.7 Hz, 2H), 7.27 (d, J ) 2.3
Hz, 1H), 7.21 (tt, J ) 7.3, 1.0 Hz, 1H), 7.01 (d, J ) 9.0 Hz, 1H), 6.93
dd, J ) 9.0, 3.1 Hz, 1H), 6.79 (d, J ) 3.1 Hz, 1H), 6.65 (d, J ) 8.4
3
CN): δ 7.57 (dd, J ) 8.2, 1.1 Hz, 2H), 7.51
(
(
JA011049N
J. AM. CHEM. SOC.
9
VOL. 124, NO. 14, 2002 3577