The element effect in nucleophilic aromatic photosubstitution (S N2Ar*)

Article abstract of DOI:10.1021/ol070910m

Photoreactions of 4-nitroanisole and the 2-halo-4-nitroanisoles (halogen == F, Cl, Br, I) with NaCN have been investigated. 4-Nitroanisole gave a novel, stable nitronate ion adduct (74%) with cyanide. For the five compounds, we report product distributions, Stern-Volmer kinetic plots, triplet lifetimes, and triplet yields, which afford rate constants for attack by the cyanide ion. Cyanide attack on the fluoride is diffusion controlled; the relative rates for attack at F, Cl, Br, and I are 27:2:2:1, respectively.

Full text of DOI:10.1021/ol070910m

ORGANIC
LETTERS
2007
Vol. 9, No. 15
2803-2806
The Element Effect in Nucleophilic
Aromatic Photosubstitution (SN2Ar*)
Gene G. Wubbels,* Kandra M. Johnson, and Travis A. Babcock
Department of Chemistry, UniVersity of Nebraska at Kearney,
Kearney, Nebraska 68849
wubbelsg@unk.edu
Received April 18, 2007
ABSTRACT
Photoreactions of 4-nitroanisole and the 2-halo-4-nitroanisoles (halogen
a novel, stable nitronate ion adduct (74%) with cyanide. For the five compounds, we report product distributions, Stern
)
F, Cl, Br, I) with NaCN have been investigated. 4-Nitroanisole gave
Volmer kinetic plots,
−
triplet lifetimes, and triplet yields, which afford rate constants for attack by the cyanide ion. Cyanide attack on the fluoride is diffusion controlled;
the relative rates for attack at F, Cl, Br, and I are 27:2:2:1, respectively.
The element effect,1 particularly that of the halogens, has
played a fundamental role in resolving mechanisms in
organic chemistry. Quantitative evidence of the effect was
central in understanding aliphatic substitution and elimination
reactions2 and nucleophilic aromatic substitutions of the SN-
2Ar type.3,4 The element effect for nucleophilic aromatic
photosubstitutions of the SN2Ar* type, reactions whose
mechanisms5 and applications6,7 have been widely studied,
has not been established. We sought to remedy this defi-
ciency to answer some basic questions about the transition
state: (1) is the element effect dominated by leaving group
effects as in thermal aliphatic substitutions and eliminations
(F , Cl < Br < I) or by σ-bond polarization and steric
effects as in thermal nucleophilic aromatic substitution (F
. Cl > Br > I)? and (2) does the fastest nucleophile-
dependent reaction from the triplet state in this graded series
show a rate constant slowed by spin forbiddenness in the
formation of the singlet σ-bonded intermediate?
The photoreaction of 4-nitroanisole (1) with the cyanide
ion in mixed aqueous media was reported by Letsinger and
co-workers,8 who found products resulting from bond
formation by the cyanide ion meta to the nitro group and a
nitrite displacement product. They also reported an intensely
absorbing stable intermediate of unknown structure (λmax 364
nm in 20% t-butyl alcohol-water) when the photolysis
solution was free of oxygen. When we irradiated 1 (0.0060
M) in oxygen-free 40% DMSO-d6-D2O (v/v) or 33%
CD3CN-D2O (v/v) containing 0.020 M NaCN in a boro-
silicate NMR tube at 313 nm at 0 or 35 °C, we found NMR
evidence for two photoproducts (2 and 3) that accounted for
26% and 74%, respectively, of the reacted starting material.
The results appear in Scheme 1. Compound 2 was expected8b
and was confirmed by enhancement of its NMR signals with
an authentic sample. The structure of nitronate ion 3 was
inferred from its spectra. It showed λmax 371 nm (ꢀ ≈ 13 000)
in 33% CH3CN-H2O and 1H NMR signals (33% CD3CN-
(1) Mueller, P. Pure Appl. Chem. 1994, 66, 1077.
(2) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic
Chemistry, 3rd ed.; Harper & Row: New York, 1987; p 374.
(3) Bunnett, J. F.; Garbisch, E. W.; Pruitt, K. M. J. Am. Chem. Soc.
1957, 79, 385.
(4) Bordwell, F. G.; Hughes, D. L. J. Am. Chem. Soc. 1986, 108, 5991.
(5) Karapire, C.; Icli, S. In Organic Photochemistry and Photobiology,
2nd ed.; Horspool, W., Lenci, F., Eds.; CRC Press: Boca Raton, 2004;
Chapter 37, pp 37-1-37-14.
(6) Specht, A.; Goeldner, M. Angew. Chem., Int. Ed. 2004, 43, 2008.
(7) Schutt, L.; Bunce, N. J. In Organic Photochemistry and Photobiology,
2nd ed.; Horspool, W., Lenci, F., Eds.; CRC Press: Boca Raton, 2004;
Chapter 38, pp 38-1-38-18.
(8) (a) Letsinger, R. L.; McCain, J. H. J. Am. Chem. Soc. 1969, 91, 6425.
(b) Letsinger, R. L.; Hautala, R. R. Tetrahedron Lett. 1969, 4205.
10.1021/ol070910m CCC: $37.00
© 2007 American Chemical Society
Published on Web 06/30/2007

Scheme 1. Photoproducts of 1 with the Cyanide Ion under
Table 1. Product Percent Yields from Cyanide Photoreactions
Air-Free Conditions
D2O) as follows (shifts relative to CD2HCN at δ 2.03): δ
6.56, 1H, d (J ) 5.7 Hz); δ 6.11, 1H, d (J ) 5.7 Hz); δ
3.79, 3H, s; δ 3.70, 1H, br s. When the solution of 2 and 3
was mixed at 25 °C with 3,5-dinitrobenzoic acid, a substance
known to oxidize dihydrobenzenes to benzenes,9 the NMR
signals of 3 were replaced by those of 2-methoxy-5-
nitrobenzonitrile having the C-6 position about 80% deu-
terated. A likely pathway to 3 involves making a strongly
basic σ-complex by meta attack of cyanide on photoexcited
1, capture of a deuteron by the σ-complex to make a
dihydrobenzene, and loss of a vinylogous alkyl nitro proton
(pKa = 7).
The photolyses of 1 and the 2-halo-4-nitroanisoles (4 (2-
F), 5 (2-Cl), 6 (2-Br), and 7 (2-I)) were carried out typically
at 0.0030 M with 0.010 M NaCN in oxygen-free 33%
CD3CN-D2O (v/v) in borosilicate NMR tubes at ca. 35 °C
with unfiltered broad-band light from 300 nm lamps (Rayonet
RPR-208). The analyses relied mostly on the integrations
of the methoxy singlets that showed baseline separations at
300 MHz in the range of 4.0 to 3.6 δ. Replacement of
halogen by cyanide was the major reaction for 4-7, giving
in all cases 2-methoxy-5-nitrobenzonitrile, whose methoxy
peak is downfield 0.06 ppm from those of the starting
materials. Its spectrum was confirmed with an authentic
sample. A minor product resulted from nitro group displace-
ment by cyanide, which gave a 0.06 ppm upfield-shifted
methoxy signal relative to starting material in all cases. The
spectrum of this minor product from the bromide was
confirmed with an authentic sample. The other minor product
was the cyanide nitronate adduct analogous to 3, which
showed in all cases a substantially upfield-shifted methoxy
signal. This was confirmed for the chloride by oxidizing the
solution containing the nitronate with 3,5-dinitrobenzoic acid,
which caused the spectrum of 2-methoxy-3-chloro-5-ni-
trobenzonitrile to appear (deuterated at C-6). The product
distributions were measured in duplicate at 20-40% conver-
sion. Results are given in Table 1.
a monitoring wavelength. Reactions were clean as shown
by sharp isosbestic points and linear fraction of reaction with
irradiation time through 10% reaction. The reaction extent
was measured between 5 and 10% conversion; the actinom-
eter was azoxybenene in ethanol.10 Plots of 1/Φ vs 1/[CN-]
were linear with correlation coefficients greater than 0.98.
The slopes, intercepts, and limiting quantum yields at
extrapolated infinite cyanide ion concentration are given in
Table 2.
Table 2. Stern-Volmer Kinetics for Photoreactions of
Nitroanisoles with the Cyanide Ion
reactant
slope
intercept intercept-1 (Φlim
)
4-nitroanisole
0.020
1.6
1.6
3.0
5.6
0.62
0.62
0.34
0.18
0.016
2-fluoro-4-nitroanisole 0.0023
2-chloro-4-nitroanisole 0.024
2-bromo-4-nitroanisole 0.029
2-iodo-4-nitroanisole
0.246
62
Triplet lifetimes and yields were obtained in oxygen-free
33% CH3CN-H2O through use of a nanosecond transient
spectrometer using 8 ns pulses at 355 nm. The triplet-triplet
absorption maximum was found at 400 ( 10 nm and was
used to monitor decay. The maximum optical density (O.D.)
at the origin of the transient allowed estimation of the triplet
yield with the assumptions that the triplet-triplet extinction
coefficient was constant for each of the five compounds and
that the largest absorbance (for the chloride) corresponded
to a triplet yield of 0.90. These results are given in Table 3.
A plausible mechanistic scheme for this reaction system
is given in Scheme 2. The production of 3 in high yield from
1 suggests that the cyano-carbon bond in any σ-complex
does not break appreciably and that decay of the σ-complexes
Stern-Volmer plots of reciprocal quantum yield vs
reciprocal cyanide ion concentration were acquired with
samples (2.0 × 10-4 M) in quartz cuvettes in oxygen-free
33% CH3CN-H2O (v/v) with NaCN at 0.020-0.0010 M.
Cyanide ion concentrations were corrected for hydrolysis as
if they were in pure water. Irradiation was at 313 nm obtained
with a chromate filter from broad-band 300 nm lamps.
Photoreactions were followed by overlaid UV scans to find
(9) Wubbels, G. G.; Halverson, A. M.; Oxman, J. D.; DeBruyn, V. H.
J. Org. Chem. 1985, 50, 4499.
(10) Bunce, N. J.; LaMarre, J.; Vaish, S. P. Photochem. Photobiol. 1984,
39, 531.
2804
Org. Lett., Vol. 9, No. 15, 2007

Table 3. Triplet Lifetimes, Decay Constants, and Triplet
Table 4. Rate Constants of Cyanide Ion Processes with Triplet
Yields for Nitroanisoles
Nitroanisoles
∑kr
kq
knitro
km-C
kX
lifetime
kd
T-T max O.D.
at 400 nm ΦISC
reactant 109 M-1s-1 109 M-1s-1 109 M-1s-1 109 M-1s-1 109 M-1s-1
compound
4-nitroanisole
(ns ( s.d.) (s -1
)
1
4
5
6
7
1.2
3.3
0.34
0.36
0.22
0.15
0.011
0.56
1.3
0.29
0.29
0.098
0.11
0.096
0.89
n.a.
2.9
0.21
0.20
0.11
58 ( 3 1.7 × 107
0.053
0.048
0.069
0.064
0.031
0.69
0.62
0.90
0.84
0.40
0.081
0.034
0.039
0.020
2-fluoro-4-nitroanisole 217 ( 6 4.6 × 106
2-chloro-4-nitroanisole 137 ( 12 7.4 × 106
2-bromo-4-nitroanisole 116 ( 1.3 8.6 × 106
5.4
2-iodo-4-nitroanisole
44.5 ( 0.4 2.2 × 107
are within a factor of 4. That this rate constant for 1 is about
10 times greater than that of 4 may reflect its statistical
advantage of two meta positions and other unknown effects
of having no halogen on the ring. The ratio of rate constants
for nitro vs meta-carbon attack is quite steady for the halogen
series, as would be expected. Because the nucleophile-
induced quenching mechanism is unknown, we do not
interpret these rate constants except to note that they correlate
with the polarizability expected for the compounds. The
quenching of the iodide is very fast and accounts for the
great inefficiency of its product formation (Φlim ) 0.016).
This contrasts with the fluoride, which shows slow quenching
and whose net limiting quantum yield (Φlim ) 0.62) is the
same as the estimated quantum yield of intersystem crossing.
The rate constants for the attack of the cyanide ion at the
halogen-bearing carbons are of primary interest. The rate for
the fluoride is at the diffusion limit, which for water is
reported for non-lyate reactants having no ionic attraction
or repulsion to be 3 × 109 M-1 s-1.11 The rate ratios for
F:Cl:Br:I are 27:2:2:1, respectively. These follow the pattern
of aromatic substitution and not aliphatic substitution or
elimination, implying that carbon-nucleophile bond forma-
tion not carbon-halogen bond fission is the principal
efficiency-determining process.
An analogous thermal nucleophilic aromatic substitution
of 1-halo-4-nitrobenzenes with sodium methoxide in metha-
nol shows relative rates of halogen displacement of 1300:
3:2:1 for F:Cl:Br:I, respectively, the iodide having a rate
constant of 1.3 × 10-7 M-1 s-1.12 If the photoreaction of
the fluoride is indeed diffusion controlled, the intrinsic energy
barrier of the reaction is zero, and the incremental barriers
for Cl, Br, and I are 1.6, 1.6, and 1.9 kcal/mol. The
increments of Arrhenius activation energy for the thermal
displacements relative to the fluoride are (for Cl, Br, and I)
3.6, 3.8, and 4.2 kcal/mol. Despite absolute rate differences
on the order of 1014, the two reaction series show comparable
halogen element effects and barrier increments. This suggests
that, despite vast differences, the photoreaction, like the
thermal one, must involve simple electron-paired bond
formation with its attendant van der Waals repulsion and
σ-bond polarization effects of the attached halogen.
Scheme 2. Photoreactions of Nitroanisoles with the Cyanide
Ion
to starting material by loss of the cyanide ion is negligible.
This implies that the fraction of σ-complexes making
products is unity (fP ) 1). With this assumption, eqs 1-3
can be readily derived.
kq
kd
k [CN ]
1
1
)
1 +
+
(1)
(2)
(3)
-
(
)
ΦX ΦISC
k
∑
r
∑
r
kd
kd
1
1
slope )
w
k )
r
∑
(
)
(
)
ΦISC
ΦISC slope
k
∑
r
kq
1
ΦISC
intercept )
1 +
(
)
k
∑
r
Equation 1 predicts the linear Stern-Volmer plots, and the
values from Tables 2 and 3 allow calculation of ∑kr and kq.
The individual rate constants in ∑kr can be extracted from
the sum with the assumption that the product yields in Table
1 are proportional to the nucleophilic attack rate constants
that give their precursor σ-complexes. Rate constants for
several of the elementary processes of this system are given
in Table 4.
These numbers disclose reassuring regularity and interest-
ing differences with changes in the halogen substituent. The
nitro group displacement (knitro) would be expected to be little
affected by the meta substituent, and indeed the rate constants
are within a factor of 3. Similarly, the rates of bond formation
at the unsubstituted meta-carbon would be expected to be
modestly affected by halogens at the meta position, and they
Attempts to understand the SN2Ar* mechanism proceeding
from a π,π* excited state have a long history.13 Two current
(11) (a) Eigen, M. Angew. Chem., Int. Ed. 1964, 3, 1. (b) Weller, A. Z.
Physik. Chem. 1958, 17, 224.
(12) Bartoli, G.; Todesco, P. E. Acc. Chem. Res. 1977, 10, 125.
(13) Cornelisse, J.; Havinga, E. Chem. ReV. 1975, 75, 353.
Org. Lett., Vol. 9, No. 15, 2007
2805

valence bond depiction of the π,π* excited state of a
halonitroanisole showing the electron hole mainly in the π
orbitals of the ring and the promoted electron in an
antibonding orbital mainly on the nitro group. Electron-paired
bond formation must cause the system to enter a funnel in
the potential energy surfaces that leads ineluctably to spin
inversion and electron demotion. This is analogous to a
recently discovered electron-paired nucleophilic reaction of
a para-benzyne biradical.16
Scheme 3. Transition State for Reaction of a Nucleophile and
a Triplet π,π* State to Make a σ-Complex Directly
Acknowledgment. Acknowledgment is made to the
donors of the Petroleum Research Fund, administered by the
American Chemical Society, for support of this work. We
thank Amy Vega and Prof. Michael Wasielewski of North-
western University for the transient measurements.
theories14,15 rationalize the predominant regiochemistry of
these reactions, including those reported here, but neither
illuminates formation of the σ-complexes that both assume.
That the fluoride σ-complex forms at the rate of diffusion
means that there is no reaction energy barrier and no spin
forbiddenness. That halogen substituents confer almost the
same effects as in the thermal reaction means that the
geometric and local electronic structures of the thermal and
photochemical transition states are similar. We envision this
as shown in Scheme 3. The first structure is a modified
1
Supporting Information Available: H NMR spectra for
Scheme 1 and Table 1, Stern-Volmer plots for Table 2, and
a typical decay curve for Table 3. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL070910M
(14) Epiotis, N. D.; Shaik, S. J. Am. Chem. Soc. 1978, 100, 29.
(15) van Riel, H. C. H. A.; Lodder, G.; Havinga, E. J. Am. Chem. Soc.
1981, 103, 7257.
(16) Perrin, C. L.; Rodgers, B. L.; O’Connor, J. M. J. Am. Chem. Soc.
2007, 129, 4795.
2806
Org. Lett., Vol. 9, No. 15, 2007