The element effect and nucleophilicity in nucleophilic aromatic photosubstitution (SNAR*). Local atom effects as mechanistic probes of very fast reactions

Article abstract of DOI:10.1021/jo702468d

(Chemical Equation Presented) Photoreactions of 4-nitroanisole and the 2-halo-4-nitroanisoles (halogen = F, Cl, Br, and I) with the nucleophiles hydroxide ion and pyridine have been investigated quantitatively to extend the findings recently communicated for cyanide ion. The halonitroanisoles on excitation form triplet π,π* states, which undergo substitution of the halogen by nucleophiles. Chemical yields of photoproducts, Stern-Volmer kinetic plots, triplet lifetimes, and triplet yields are reported for the five compounds with the three nucleophiles. Following a standard kinetic treatment, 73 rate constants are determined for elementary reactions of the triplets including quenching and various nucleophilic addition processes. The photoadditions are roughly 14 orders of magnitude faster than thermal counterparts. Rate constants for attack at the fluorine-bearing carbon of triplet 2-fluoro-4-nitroanisole are 2.9 × 10⁹, 1.3 × 10⁹, and 6.3 × 10⁸ M^-1 s^-1 for cyanide ion, hydroxide ion, and pyridine, respectively. The relative rates for attack at the halogen-bearing carbons for F/Cl/Br/I are 27:1.9:1.9:1 (cyanide ion), 29:2.6:2.4:1 (hydroxide ion), and 39:3.9: 3.5:1 (pyridine), respectively. The relative nucleophilicities vary somewhat with the attack site; they are about 5:2:1 for cyanide ion, hydroxide ion, and pyridine for attack at the halogen-bearing carbons. The trend of the element effect opposes that of aliphatic substitution and elimination but is similar in size and parallel to that of thermal nucleophilic aromatic substitution. Relative nucleophilicities in the photoreactions are also similar to those of comparable but vastly slower thermal reactions. The findings imply that the efficiency-determining step of the halogen photosubstitution is simple formation of a σ-complex through electron-paired bonding within the triplet manifold.

Full text of DOI:10.1021/jo702468d

The Element Effect and Nucleophilicity in Nucleophilic Aromatic
Photosubstitution (SN2Ar*). Local Atom Effects as Mechanistic
Probes of Very Fast Reactions
Gene G. Wubbels,* Toby R. Brown, Travis A. Babcock, and Kandra M. Johnson
Department of Chemistry, UniVersity of Nebraska at Kearney, Kearney, Nebraska 68849
wubbelsg@unk.edu
ReceiVed NoVember 17, 2007
Photoreactions of 4-nitroanisole and the 2-halo-4-nitroanisoles (halogen ) F, Cl, Br, and I) with the
nucleophiles hydroxide ion and pyridine have been investigated quantitatively to extend the findings
recently communicated for cyanide ion. The halonitroanisoles on excitation form triplet π,π* states,
which undergo substitution of the halogen by nucleophiles. Chemical yields of photoproducts, Stern-
Volmer kinetic plots, triplet lifetimes, and triplet yields are reported for the five compounds with the
three nucleophiles. Following a standard kinetic treatment, 73 rate constants are determined for elementary
reactions of the triplets including quenching and various nucleophilic addition processes. The photoadditions
are roughly 14 orders of magnitude faster than thermal counterparts. Rate constants for attack at the
fluorine-bearing carbon of triplet 2-fluoro-4-nitroanisole are 2.9 × 109, 1.3 × 109, and 6.3 × 108 M-1
s-1 for cyanide ion, hydroxide ion, and pyridine, respectively. The relative rates for attack at the halogen-
bearing carbons for F/Cl/Br/I are 27:1.9:1.9:1 (cyanide ion), 29:2.6:2.4:1 (hydroxide ion), and 39:3.9:
3.5:1 (pyridine), respectively. The relative nucleophilicities vary somewhat with the attack site; they are
about 5:2:1 for cyanide ion, hydroxide ion, and pyridine for attack at the halogen-bearing carbons. The
trend of the element effect opposes that of aliphatic substitution and elimination but is similar in size and
parallel to that of thermal nucleophilic aromatic substitution. Relative nucleophilicities in the photoreactions
are also similar to those of comparable but vastly slower thermal reactions. The findings imply that the
efficiency-determining step of the halogen photosubstitution is simple formation of a σ-complex through
electron-paired bonding within the triplet manifold.
Introduction
intermediate singlet σ-complex,5 but there is little evidence for
the σ-complex. It occurred to us that this mechanism could be
studied definitively by use of the element effect of halogens
and relative nucleophilicities. Photochemists have made little
mechanistic use of local substituent effects, possibly because
of the limitation that substituent changes must little affect the
chromophore and its photophysics. Avoidance of such perturba-
Important aspects of the mechanism of nucleophilic aromatic
photosubstitution of the SN2Ar*-type reaction remain unclear.
These reactions, whose mechanisms1,2 and applications3,4 have
been studied extensively, are generally agreed to involve an
(1) Terrier, F. Nucleophilic Aromatic Displacement: The Influence of
the Nitro Group; VCH Publishers: New York, 1991; Chapter 6.
(2) Karapire, C.; Icli, S. In Organic Photochemistry and Photobiology,
2nd ed.; Horspool, W., Lenci, F., Eds.; CRC Press: Boca Raton, FL, 2004;
Chapter 37, pp 37-1- 37-14.
(4) Schutt, L.; Bunce, N. J. In Organic Photochemistry and Photobiology,
2nd ed.; Horspool, W., Lenci, F., Eds.; CRC Press: Boca Raton, FL, 2004;
Chapter 38, pp 38-1- 38-18.
(3) Specht, A.; Goeldner, M. Angew. Chem., Int. Ed. 2004, 43, 2008.
(5) Cornelisse, J.; Havinga, E. Chem. ReV. 1975, 75, 353.
10.1021/jo702468d CCC: $40.75 © 2008 American Chemical Society
Published on Web 01/24/2008
J. Org. Chem. 2008, 73, 1925-1934
1925

Wubbels et al.
SCHEME 1. Photoproducts of 1 with Cyanide Ion under
Oxygen-Free Conditions
tion with variation of the nucleofuge, as well as the nucleophile,
seemed possible for the case of SN2Ar* reactions.
The element effect is a named entity in physical organic
chemistry.6 It refers to rate ratios in a reaction having reactants
substituted with different atoms of the same group of the
Periodic Table. The element effect, especially of the halogens,
has played a fundamental role in resolving mechanisms in
organic chemistry. The effect was central in understanding
aliphatic substitution and elimination reactions7 and nucleophilic
aromatic substitution reactions of the SN2Ar type.8,9 It seemed
possible at the least that we could establish whether the
efficiency-determining transition state of the photosubstitution
was dominated by leaving group effects as in thermal aliphatic
substitution and elimination (F , Cl < Br < I) or by σ-bond
polarization and steric effects as in thermal nucleophilic aromatic
substitution (F . Cl > Br > I).10 That we know little about
relative nucleophilicity in photoreaction mechanisms may result
from having discovered few reactions in which nucleophilic
attack occurs directly on the excited-state molecule. Since
nucleophilicity reflects local atomic and molecular properties
independent of the photophysics of the substrate, this also
seemed an auspicious probe.
109 M-1 s-1); they are roughly 1014 times faster than their
thermal counterparts. The influence of local structural and
electronic effects of substituents and of nucleophilicity on such
fast substitution reactions has not been assessed. Moreover, the
reaction from the excited state plus nucleophile to the σ-complex
involves a large release of energy12 and an electron spin
inversion. The effect, if any, of the spin inversion on the rate
has also not been established.
Establishing the halogen element effect and relative nucleo-
philicities for the elementary rate constants of a suitable series
of photosubstitution substrates promised to answer several of
these questions. The 2-halo-4-nitroanisole series seemed likely
to suffice because the spectroscopy and photophysics are
dominated by the nitrophenyl ether chromophore, efficiently
giving a triplet π,π* state on photoexcitation13-16 that would
be expected to be little affected by halogen substitution.
Moreover, Havinga and co-workers had shown5 that several
2-halo-4-nitroanisoles undergo photosubstitution of the halogen
by hydroxide ion.
Two models with different theoretical bases rationalize the
regioselectivity of the SN2Ar* reaction,11,12 but neither provides
insight about the occurrence of the σ-complex that both assume
or the proximate transition states. The transition state postulated
for SN2Ar* reactions of nitrophenyl ethers involves formation
of a σ-complex from attack of a nucleophile on a triplet π,π*
excited state.5 This postulate, however, leaves several
questions open. Complexes5 or exciplexes13,14 have been sug-
gested to result from the encounter of excited state and
nucleophile on the basis of some transient spectroscopy studies,
while other studies15,16 have found no need for exciplexes.
Indeed, another mechanism, named SN(ET)Ar*,1 features a
different transition state involving electron transfer from nu-
cleophile to excited state.17-19 It entails para-to-nitro regiose-
lectivity for substitution, but several cases with amine nucleo-
philes have been shown likely to proceed by the SN2Ar*
mechanism involving a fast sigmatropic rearrangement of a meta
σ-complex to a para σ-complex.20 The transition state for SN-
2Ar* mediates the fastest nucleophilic reactions known (k =
Results
Photolyses of 4-nitroanisole (1) with cyanide ion in mixed
aqueous solutions were carried out by Letsinger and co-
workers.21 They reported a nitrite displacement product and
products resulting from bond formation by cyanide ion meta to
the nitro group. When the photolysis medium was free of
oxygen, they observed an intensely absorbing photoproduct of
unknown structure that was stable in solution (λmax ) 364 nm
in 20% t-butyl alcohol/water). When we irradiated 1 in oxygen-
free 33% CD3CN-D2O (v/v) containing NaCN at 313 nm at 0
1
or 35 °C, we found H 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 expected21b and was confirmed 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-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 3,5-dinitrobenzoic acid, a substance known
to oxidize dihydrobenzenes to benzenes,22 was added to the
solution of 2 and 3 at 25 °C, the NMR signals of 3 were replaced
slowly by those of 2-methoxy-5-nitrobenzonitrile with the C-6
position about 80% deuterated. That a nitronate ion is a stable
photoproduct of 1 with the nucleophile, cyanide ion, is without
precedent.
(6) Mueller, P. Pure Appl. Chem. 1994, 66, 1077.
(7) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic
Chemistry, 3rd ed.; Harper & Row: New York, 1987; p 374.
(8) Bunnett, J. F.; Garbisch, E. W.; Pruitt, K. M. J. Am. Chem. Soc.
1957, 79, 385.
(9) Bordwell, F. G.; Hughes, D. L. J. Am. Chem. Soc. 1986, 108, 5991.
(10) A preliminary report of the element effect in photosubstitution by
cyanide ion has appeared: Wubbels, G. G.; Johnson, K. M.; Babcock, T.
A. Org. Lett. 2007, 9, 2803.
(11) Epiotis, N. D.; Shaik, S. J. Am. Chem. Soc. 1978, 100, 29.
(12) van Riel, H. C. H. A.; Lodder, G.; Havinga, E. J. Am. Chem. Soc.
1981, 103, 7257.
(13) Varma, C. A. G. O.; Tamminga, J. J.; Cornelisse, J. J. Chem. Soc.,
Faraday Trans. 2 1982, 78, 265.
(14) van Eijk, A. M. J.; Huizer, A. H.; Varma, C. A. G. O.; Marquet, J.
J. Am. Chem. Soc. 1989, 111, 88.
(15) van Zeijl, P. H. M.; van Eijk, L. M. J.; Varma, C. A. G. O. J.
Photochem. 1985, 29, 415.
(16) Bonhila, J. B. S.; Tedesco, A. C.; Nogueira, L. C.; Diamantino, M.
T. R. S.; Carreiro, J. C. Tetrahedron 1993, 49, 3053.
(17) Yokoyama, K.; Nakamura, J.; Mutai, K.; Nagakura, S. Bull Chem.
Soc. Jpn. 1982, 55, 317.
(18) Wubbels, G. G.; Snyder, E. J.; Coughlin, E. B. J. Am. Chem. Soc.
1989, 110, 2543.
The photolyses of the 2-halo-4-nitroanisoles (4 (2-F), 5 (2-
Cl), 6 (2-Br), and 7 (2-I)) with cyanide ion were carried out
(21) (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.
(19) Wubbels, G. G.; Ota, N.; Crosier, M. L. Org. Lett. 2005, 7, 4741.
(20) Wubbels, G. G.; Johnson, K. M. Org. Lett. 2006, 8, 1451.
(22) Wubbels, G. G.; Halverson, A. M.; Oxman, J. D.; DeBruyn, V. H.
J. Org. Chem. 1985, 50, 4499.
1926 J. Org. Chem., Vol. 73, No. 5, 2008

Nucleophilic Aromatic Photosubstitution
TABLE 1. Product Percent Yields from Photoreactions of 4-7
with NaCN by NMR Analysis
TABLE 2. Product Percent Yields from Photoreactions of 4-7
with NaOH by NMR Analysis
TABLE 3. UV/Vis Properties in 33% CH3CN/H2O, 0.0050 M
NaOH of Photoproducts of 4-7 with NaOH for Quantitative
Product Analysis
typically at 0.003 M with 0.01 M NaCN in oxygen-free 33%
CD3CN/D2O (v/v) in NMR tubes at ca. 35 °C with unfiltered
broad-band light at 300 nm. The methoxy singlets of photo-
products showed baseline separations at 300 MHz in the
range of 4.0-3.6 δ. Integration of these signals, and the
respective downfield signals in most cases, allowed yield
estimations. 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 that of the starting materials. Its spectrum was
confirmed with an authentic sample. A minor product resulted
from nitro group displacement by cyanide, which gave a 0.06
ppm upfield-shifted methoxy signal relative to starting materials
in all cases. These were confirmed with authentic samples for
the chloride and bromide. 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-nitrobenzonitrile to appear
(deuterated at C-6). The product distributions were measured
in duplicate at 20-40% conversion. The results are given in
Table 1.
photoreaction of 6. The other photoproduct 3-halo-4-methoxy-
phenols showed almost identical spectra. Quantitative analysis
of these products by NMR was problematic, however, especially
for the halonitroanisoles that reacted less efficiently. The 3-halo-
4-methoxyphenols were photolabile in alkaline 33% CD3CN/
D2O. Photolysis of 3-bromo-4-methoxyphenol in alkaline
solution caused photohydrolysis of the methoxy group, giving
methanol, a photoreaction that has precedent.5 The secondary
photolysis frustrated the determination of yields of the minor
products from the substances that reacted less efficiently. In
those cases, the methanol signal was disregarded, and we used
integrations of the weak downfield NMR signals at early
conversions for specific minor products. We judge the results
in Table 2 to be quite reliable for 4-6 but uncertain for the
minor products of 7.
Because of the uncertainty, another method of analysis with
quantitative UV/vis spectra was developed. Extinction coef-
ficients were measured carefully for authentic samples of the
photoproducts, and spectral overlays (200-600 nm) were made
for each of the photoreactions of 4-7 with hydroxide ion, all
in 33% acetonitrile/water. All photoreactions were carried to
completion, and they showed sharp isosbestic points. The
electronic spectra used are in Table 3.
The photolyses of 1 and 4-7 with hydroxide ion were carried
out as above but with NaOH at 0.01 M. The products were
analyzed by NMR, but this analysis was inferior to a UV/vis
analysis described below. The photolyses of 1 at 3 and 26 °C
with hydroxide ion in aqueous media are reported23 to give
4-methoxyphenol (80%) and 4-nitrophenol (20%). The products
and yields from 1 with NaOH under our conditions in 33% CD3-
CN/D2O were the same. The photolyses of 4-7 with hydroxide
ion gave in all cases 2-methoxy-5-nitrophenol as the major
1
product. Quantification of this product was done by H NMR
integration using the entire spectrum, but especially the methoxy
peak about 0.2 ppm upfield from that of the starting materials.
Displacement of the methoxy group of 4-7 gave a minor
product (2-halo-4-nitrophenol) in all cases plus methanol, whose
singlet appeared 0.7 ppm upfield of the methoxy signal of
starting materials. Here also, the entire spectrum was used for
quantification except for the case of 4, where the downfield
signals were too weak for accurate analysis. The spectra of the
methoxy displacement products and methanol were confirmed
with authentic samples. Displacement of the nitro group also
gave rise to minor photoproducts, the 3-halo-4-methoxyphenols.
This was shown by the coincidence of the spectrum of authentic
3-bromo-4-methoxyphenol with a minor product from the
The UV/vis analysis was rather blind to the secondary
photochemistry of the 3-halo-4-methoxyphenols because their
extinctions and those of their photoproducts are small relative
(23) Letsinger, R. L.; Ramsay, O. B.; McCain, J. H. J. Am. Chem. Soc.
1965, 87, 2945.
J. Org. Chem, Vol. 73, No. 5, 2008 1927

Wubbels et al.
TABLE 4. Product Percent Yields from Photoreactions of 4-7
with NaOH by UV/Vis Analysis
to those of 2-methoxy-5-nitrophenol and the 2-halo-4-nitrophe-
nols. The spectrum at completion of each photoreaction was
matched by iteration with variable compositions of three
photoproducts totaling 100%. The results are in Table 4. It may
be noted that these results are very close to those above for
compounds 4-6 and slightly different for the minor products
from 7. We have greater confidence in the UV/vis analyses and
have used those results in the kinetic analyses.
FIGURE 1. Stern-Volmer plots for photoreactions of nitroanisoles
with NaCN in 33% acetonitrile/water: ) 4; 0 1; ∆ 5; × 6; O 7.
The photoreaction of pyridine with 1 in aqueous media is
reported23 to give exclusively displacement of nitrite ion,
producing a pyridinium nitrite salt, and with 6 to give
exclusively displacement of bromide, producing a pyridinium
bromide salt.24 We confirmed these findings for 1 and 6 for
our irradiation conditions by NMR and by UV/vis. We found
by UV/vis that compounds 4, 5, and 7 also photoreact cleanly
to give the same pyridinium ion given by 6.
Stern-Volmer plots of reciprocal quantum yield versus
reciprocal nucleophile concentration were acquired with
samples of 1 and 4-7 (2.2 × 10-4 M) in quartz cuvettes in
oxygen-free 33% CH3CN/H2O (v/v) with NaCN at 0.020-
0.0010 M, NaOH at 0.010-0.0010 M, and pyridine at 0.040-
0.0020 M. Cyanide ion concentrations were corrected for
hydrolysis as if they were in pure water. Irradiation at 313 nm
was carried out with a chromate filter with light from broad-
band 300 nm lamps. The photoreactions were followed to
completion by overlaid UV scans to find a monitoring wave-
length. Reactions were clean as shown by sharp isosbestic points
and linear fraction of reaction with irradiation time through 10%
reaction. Reaction extent was measured between 5 and 10%
conversion; the actinometer was azoxybenzene in ethanol.25
Plots of 1/Φ versus 1/[nucleophile], as shown in Figures 1-3,
were linear. The slopes, intercepts, and limiting quantum yields
at extrapolated infinite nucleophile concentration are given in
Table 5.
FIGURE 2. Stern-Volmer plots for photoreactions of nitroanisoles
with NaOH in 33% acetonitrile/water: ) 4; 0 1; ∆ 5; × 6; O 7.
Triplet lifetimes and yields were obtained in oxygen-free 33%
CH3CN/H2O through use of a nanosecond transient spectrom-
eter. The instrument utilized 8 ns pulses at 355 nm from a
frequency-tripled Nd:YAG laser. Samples were contained in 1
cm quartz cuvettes, and the irradiation and monitoring beams
were collinear. The triplet-triplet absorption maximum was
established in each case near 400 nm and was used to monitor
decay. The maximum optical density (OD) 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 5) corresponded to a triplet yield
FIGURE 3. Stern-Volmer plots for photoreactions of nitroanisoles
with pyridine in 33% acetonitrile/water: ) 4; 0 1; ∆ 5; × 6; O 7.
of 0.90. The basis for this assignment is that ΦISC cannot exceed
unity, and the highly efficient reactions of 1 and 4 with cyanide
ion as measured by Φlim (Table 5) are approximately equal to
ΦISC if the value for 5 is set at 0.9. The results are given in
Table 6.
Discussion
The production of 3 in high chemical yield and quantum yield
from the photoreaction of 1 with cyanide ion can be rationalized
by the sequence shown in Scheme 2. The σ-complex formed
from the reaction of photoexcited 1 with cyanide ion would be
(24) Gamson, E. P. Ph.D. Dissertation, Northwestern University, 1970.
(25) Bunce, N. J.; LaMarre, J.; Vaish, S. P. Photochem. Photobiol. 1984,
39, 531.
1928 J. Org. Chem., Vol. 73, No. 5, 2008

Nucleophilic Aromatic Photosubstitution
TABLE 5. Stern-Volmer Parameters for Photoreactions of
Nitroanisoles with Cyanide Ion, Hydroxide Ion, and Pyridine
SCHEME 3. General Mechanistic Scheme for Nucleophilic
Aromatic Photosubstitution
intercept-1
Φlim
reaction
slope
intercept
1 + CN-
0.020
0.0023
0.024
0.029
0.246
0.26
0.0051
0.042
0.055
0.63
5.4
0.012
0.13
0.18
3.3
1.6
1.6
3.0
5.6
62
6.0
1.9
2.4
3.6
130
325
3.3
4.2
6.8
92
0.62
0.62
0.34
0.18
0.016
0.17
0.54
0.42
0.28
0.0077
0.0031
0.31
0.24
0.15
4 + CN-
5 + CN-
6 + CN-
7 + CN-
1 + OH-
4 + OH-
5 + OH-
6 + OH-
7 + OH-
1 + pyridine
4 + pyridine
5 + pyridine
6 + pyridine
7 + pyridine
should be readily lost to make 3. This implies that any
σ-complexes made by attack of cyanide ion are unlikely to decay
appreciably to starting materials by loss of cyanide and,
therefore, that the fraction of each cyanide σ-complex that makes
a detectable product is approximately unity.
0.011
TABLE 6. Triplet Lifetimes, Decay Constants, and Yields of
Nitroanisoles in 33% Acetonitrile-Water
A plausible mechanistic scheme for this reaction system is
given in Scheme 3. Evidence from the literature13-16 and from
our flash photolysis experiments indicates that photoexcitation
of 1 and 4-7 populates the triplet state quite efficiently. We
consider first the case of the photochemistry with cyanide ion
because of the simplification that the product yields should
reflect the yields of intermediate σ-complexes, that is, fP = 1
for each product. Equations 1-3 can be derived readily for the
reaction system. Equation 1 predicts the linear Stern-Volmer
lifetime
(ns ( s.d.)
T-T max OD
compound
kd (s-1
)
at 400 nm
ΦISC
1
4
5
6
7
58 ( 3
217 ( 6
137 ( 12
116 ( 1.3
44.5 ( 0.4
1.7 × 107
4.6 × 106
7.4 × 106
8.6 × 106
2.2 × 107
0.053
0.048
0.069
0.064
0.031
0.69
0.62
0.90
0.84
0.40
SCHEME 2. Partitioning of the meta σ-Complex from
Photoexcited 1 Plus Cyanide Ion
kq
kd
k [CN ]
1
1
)
1 +
+
(1)
(2)
(3)
-
(
)
Φx ΦISC
k
∑
r
∑
r
kd
kd
1
ΦISC
1
slope )
w
k )
r
∑
(
)
(
)
ΦISC slope
k
∑
r
kq
1
ΦISC
intercept )
1 +
(
)
k
∑
r
plots, and the values from Tables 5 and 6 allow calculation of
∑kr and kq. The individual rate constants in ∑kr can be extracted
from the sum with the assumption that the yields of products
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
reported in Table 7.
expected to be strongly basic (conjugate acid pKa = 40) yet
would undergo deuteration relatively slowly. For a comparable
system, a rate constant of 5 × 107 M-1 s-1 is reported for the
protonation of toluene anion (conjugate acid pKa = 41) by water
in THF.26 The reaction rate would be slowed further in our case
by an isotope effect. This implies that cyanide ion has the
opportunity to depart from the σ-complex. This must not occur
appreciably, however, in view of the high chemical and quantum
yields of 3. Cyanide ion, unlike most other nucleophiles, is
sufficiently sticky to make a persistent complex that undergoes
protonation (deuteration) on carbon to make a dihydrobenzene.27
The dihydrobenzene has an acidic vinylogous R-nitro proton
that is also an R-cyano proton. It should have a pKa = 7 and
The hydroxide ion reactions require one adjustment. The
σ-complexes for displacement of halide ion and nitrite ion would
not be expected to partition appreciably back to starting material
since hydroxide ion (conjugate acid pKa ) 15.7) is a much
poorer leaving group than nitrite ion (conjugate acid pKa ) 3.4)
or the poorest leaving halogen, fluoride ion (conjugate acid pKa
) 3.5). The yields of the halide and nitrite displacement
products, therefore, should reflect the σ-complex precursor
populations. The methoxide displacement, however, would have
hydroxide ion loss competing with methoxide ion loss. Since
these are comparable leaving groups, we assume that the yield
of methoxide-substituted product represents half of the precursor
σ-complex, which requires a corresponding adjustment of the
relevant rate constant. This assumption and those described for
cyanide ion yield the elementary rate constants for the hydroxide
reactions in Table 8.
(26) Dorfman, L. M.; Sujdak, R. J.; Bockrath, B. Acc. Chem. Res. 1976,
9, 352.
(27) We are not the first to discover that cyanide ion makes persistent
addition complexes with aromatic substrates; see: Bunnett, J. F.; Zahler,
R. E. Chem. ReV. 1952, 52, 273.
J. Org. Chem, Vol. 73, No. 5, 2008 1929

Wubbels et al.
TABLE 7. Rate Constants of Cyanide Ion Processes with Triplet Nitroanisoles
Σkr
kq
knitro
km-C
kX
kX
relative
reactant
109 M-1 s-1
109 M-1 s-1
109 M-1 s-1
109 M-1 s-1
109 M-1 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
0.081
0.034
0.039
0.020
27
1.9
1.9
1.0
5.4
TABLE 8. Rate Constants of Hydroxide Ion Processes with Triplet Nitroanisoles
Σkr
kq
knitro
kOMe
kX
kX
relative
reactant
109 M-1 s-1
109 M-1 s-1
109 M-1 s-1
109 M-1 s-1
109 M-1 s-1
1
4
5
6
7
0.095
1.4
0.20
0.19
0.087
0.29
0.24
0.22
0.38
4.5
0.076
0.043
0.029
0.032
0.018
0.032
0.084
0.025
0.028
0.016
n.a.
1.3
0.12
0.11
0.045
29
2.6
2.4
1.0
TABLE 9. Rate Constants for Pyridine Processes with Triplet
Nitroanisoles
by cyanide ion is steady in the range of 3-5 for 4-7, as would
be expected. The comparable ratio for nitro versus methoxy
attack by hydroxide ion is also quite steady for the halogen
series in the range of 0.5-1.
Σkr
kq
knitro
kX
kX
reactant 109 M-1 s-1 109 M-1 s-1 109 M-1 s-1 109 M-1 s-1 relative
1
4
5
6
7
0.0046
0.63
0.063
0.057
0.016
1.0
0.0046
n.a.
0.63
0.063
0.057
0.016
Since little is known about nucleophile-induced quenching
mechanisms, we note only a few highlights. The quenching by
cyanide ion correlates with the polarizability expected for
the nitroaromatic compounds. The rates of quenching of the
iodide by cyanide ion and hydroxide ion are at or above
the rate of diffusion, and these account for the great
inefficiency of photoproduct formation from 7 (Φlim ) 0.016
and 0.0077, respectively). These contrast especially with the
cyanide ion reactions of 1 and 4, which show slow quenching
and whose limiting quantum yields (Φlim ) 0.62 and 0.62)
are approximately the same as the estimated quantum yields
of intersystem crossing. That the quenching by hydroxide ion
occurs at a fairly constant rate for 1 and 4-6 and does not
correlate with polarizability may stem from a quenching
possibility that hydroxide ion has and cyanide ion does not
have. Nucleophilic attack at an unsubstituted meta carbon by
cyanide ion generates a photoproduct, but the corresponding
hydroxide ion σ-complex would lose hydroxide ion, resulting
in quenching. The quenching by pyridine also does not vary
systematically with halogen substitution and, except for the
iodide, is similar in size to that of hydroxide ion. This
suggests that pyridine also quenches by the nucleophilic
attack process described above for hydroxide ion. These findings
are similar to those of Letsinger and McCain21a for a related
system.
0.67
0.18
0.27
0.59
39
3.9
3.5
1.0
Partitioning of σ-complexes at the halogen-bearing carbon
back to starting materials for the photosubstitutions by pyridine
(conjugate acid pKa ) 5.3) seems unlikely for Cl, Br, and I,
the anions of which all have conjugate acid pKa values of -7
or below and should be relatively fast leaving groups. Partition-
ing back to starting materials could occur for the displacements
of nitrite ion from 1 (conjugate acid pKa ) 3.4) and fluoride
ion from 4 (conjugate acid pKa ) 3.5). Reversion seems likely,
however, to be a minor process in each case, and we have at
this time no basis for assessing it. We have assumed no
partitioning of σ-complex intermediates back to starting materi-
als for the elementary rate constants for the pyridine reactions
summarized in Table 9.
The rate data in Tables 7-9 display a wealth of subtle effects
of structural changes in these reactions. The nitro group
displacements (knitro) would be expected to be little affected by
meta substituents, and indeed the rate constants for attack on 1
and 4-7 leading to nitrite displacement are within a factor of
3-4 for cyanide ion and for hydroxide ion. For these displace-
ments, the cyanide ion rate constants are 3.5-7 times faster
than those of hydroxide ion and 63 times faster than that of
pyridine for the one comparison available. These nucleophi-
licities compare surprisingly closely with an averaged nucleo-
philicity measure for aqueous solution with saturated carbon
substrates for which cyanide ion reacts about 4 times faster than
hydroxide ion and 31 times faster than pyridine.28 Similarly,
the rates of bond formation at the unsubstituted meta carbon
by cyanide ion would be expected to be modestly affected by
halogens at the meta position, and they 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 versus meta carbon attack
Our major interest is in the rate constants for the attack of
nucleophiles at the halogen-bearing carbon. The rate for excited
fluoride 4 plus cyanide ion 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 29
. The rate ratios
for F/Cl/Br/I are 27:1.9:1.9:1, respectively. The fastest rate for
hydroxide ion is about half the rate of diffusion, and the relative
rates for F/Cl/Br/I are 29:2.6:2.4:1, respectively. The fastest rate
for pyridine is about one-fifth of the rate of diffusion, and the
relative rates for F/Cl/Br/I are 39:3.9:3.5:1, respectively. All of
these element effects follow the pattern of aromatic substitu-
tion8,9 and not aliphatic substitution or elimination,7 implying
that carbon-nucleophile bond formation not carbon-halogen
(29) (a) Eigen, M. Angew. Chem., Int. Ed. Engl. 1964, 3, 1. (b) Weller,
A. Z. Phys. Chem. 1958, 17, 224.
(28) Wells, P. R. Chem. ReV. 1963, 63, 171.
1930 J. Org. Chem., Vol. 73, No. 5, 2008

Nucleophilic Aromatic Photosubstitution
bond fission is the principal efficiency-determining process.
These findings, like those for the famous thermal case,8 provide
strong evidence against a concerted mechanism or any other
mechanism involving C-X bond fission in the efficiency-
determining step. They support efficiency-determining inter-
mediate σ-complex formation.
and electronically similar to that of ground state nucleophilic
transition states.
Attempts to understand the SN2Ar* mechanism proceeding
from a triplet π,π* state have a long history.1,5 The regiochemi-
cal and reactivity questions are embedded in the reaction
of a singlet nucleophile with a triplet excited aromatic
substrate. The reaction proceeds with a large energy release to
form energetic, singlet intermediates before reaching the singlet
products. The sequence is a classical problem in photochemical
mechanisms31 that has been only slightly elucidated despite
extensive study. Our results shed some new light on this
mechanism.
The thermal substitutions of 1-halo-4-nitrobenzenes with
sodium methoxide in methanol show 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 30
.
This reaction
series is comparable to our photochemical series in using a
simple hard atom nucleophile in a protic solvent. Since the
photoreaction of fluoride 4 with cyanide ion is diffusion-
controlled, the intrinsic energy barrier of the reaction is 0. The
incremental Arrhenius activation energy barriers for Cl, Br,
and I are 1.6, 1.6, and 1.9 kcal/mol for cyanide ion. For
hydroxide ion, the increments of activation energy (vs the
fluoride) for Cl, Br, and I are 1.4, 1.5, and 2.0 kcal/mol,
respectively, and for pyridine, the corresponding increments are
1.4, 1.4, and 2.2 kcal/mol. For the thermal displacements by
methoxide ion,30 the increments of Arrhenius activation
energy relative to the fluoride (for Cl, Br, and I) are 3.6, 3.8,
and 4.2 kcal/mol. Thus, despite absolute rate differences on the
order of 1014, the thermal and the photochemical reaction series
show comparable halogen element effects and barrier incre-
ments. The element effect in the photoreaction is damped in
rate by roughly a factor of 40, or about 2 kcal/mol in incremental
activation energy. This strongly suggests that the photoreaction,
like the vastly slower thermal one, must involve simple electron-
paired bond formation with its attendant local van der Waals
repulsion and σ-bond polarization effects of the attached
halogen.
The theory of Epiotis and Shaik11 predicts regioselectivity
in SN2Ar* reactions based on frontier molecular orbital theory.
It postulates that reaction will be favored at ring carbon atoms
having a maximal ground state HOMO coefficient and a
minimal ground state LUMO coefficient. Semiempirical cal-
culations (AM1) in Spartan ’04 reveal that the maximum of
the difference of absolute value of the HOMO coefficient minus
absolute value of the LUMO coefficient predicts the major
product in each case reported here. In most cases, however,
the yields of minor products do not correlate with the coefficient
differences. It should be noted that prediction of the major
products for these cases is not risky and furnishes little
validation of the theory. It would do as well to predict simply
that maximum detectable reaction occurs meta to the nitro
group, and it appears that the maximum ground state
coefficient difference serves merely to identify that position.
Indeed, this theory seems to us to lack justification since it
postulates excited-state regioselectivity based on orbitals that
do not exist in the reacting excited molecules. The model is
based on purported properties of the initial state, a known
weakness in predicting regioselectivity in aromatic substrates.32
Moreover, the reacting molecules are not of the same multiplic-
ity as the molecules calculated. The argument11 that the triplet
should react like the excited singlet because spin-orbit coupling
would be large and would convert the triplet encounter complex
to a singlet encounter complex before forming the singlet
σ-complex seems wholly without justification for the cases
reported here. Despite its success for the major products, we
do not believe that the Epiotis-Shaik model provides a
satisfactory rationale for the regioselectivity and reactivity of
SN2Ar* reactions.
The other extant rationale of regioselectivity of SN2Ar*
reactions was put forward by van Riel, Lodder, and Havinga.12
It postulates that the energy gap law for radiationless electronic
transitions, that is, that internal conversions between states close
in energy are faster than those between states far apart in energy,
should apply to the selection of favorable transition states for
photosubstitution. Since singlet meta-to-nitro σ-complexes or
those for displacement of the nitro group are little stabilized by
resonance, they are much less stable than the ortho or para
σ-complexes. Thus the transition from the triplet encounter
complex to the less stable (meta) σ-complexes was judged12 to
be faster than that of the more stable (ortho or para) σ-com-
plexes. This model also successfully rationalizes the products
of the reactions reported here, although it cannot distinguish
major from minor products among those products favored by
the model.
The nucleophilicities evident in the halogen photosubstitutions
are similar to those for the comparatively slow thermal substitu-
tions. Cyanide ion attacks the halogen-bearing carbons 1.8-
2.4 times faster than hydroxide ion does and 3.3-6.9 times faster
than pyridine does. For aqueous solution with saturated carbon
substrates, cyanide ion reacts on average about 4 times faster
than hydroxide ion and 31 times faster than pyridine,28 that being
a range of 2 kcal in incremental activation energy. Thus
nucleophilicities, like the element effects, in the photoreactions
are damped in rate by roughly a factor of 6, or about 1 kcal/
mol in incremental activation energy. Again, the remarkable
similarity of local effects despite the huge difference in rates
suggests that the transition states are similar, namely, electron-
paired formation of a bond through nucleophilic attack. That
the behavior of pyridine is so similar to that of hydroxide ion
and cyanide ion suggests, moreover, that the powerful forces
of solvation and desolvation for the ions (that would be much
diminished for neutral pyridine) do not appear in the relative
rates.
It may be noted that our sparse data on nucleophilicities for
attack at the nitro-bearing carbon show a similar picture. They
span a range of about 60 in rate (pyridine/hydroxide ion/cyanide
ion all for 1 are 1:17:63) that is 2-fold larger than that for the
thermal reactions of these nucleophiles. This corresponds,
however, to only 2.5 kcal in incremental activation energy
difference, which is close to the 2.0 kcal range for the thermal
case. This also argues that the transition state leading to the
σ-complex for nitro displacement is, at the local level, sterically
(31) Havinga, E. ReactiVity of the Photoexcited Molecule; Wiley: New
York, 1967; p 201.
(32) Dewar, M. J. S. The Molecular Orbital Theory of Organic
Chemistry; McGraw-Hill: New York, 1969; Chapter 6.
(30) Bartoli, G.; Todesco, P. E. Acc. Chem. Res. 1977, 10, 125.
J. Org. Chem, Vol. 73, No. 5, 2008 1931

Wubbels et al.
SCHEME 4. Modified Valence Bond Depiction of Reaction
of a Nucleophile with a Triplet π,π* Excited State of a
2-Halo-4-nitroanisole
more electrons would be present at these positions than can
be accommodated in a two-electron bond. Alternatively, ap-
proach of the nucleophile at C2, C4, or C6 encounters
cationic carbon, which should afford two-electron bond
formation with little or no activation energy. Any activation
energy required would reflect local substituent and nucleophile
effects. This makes a very good summary of the facts we
observe.
FIGURE 4. Odd electron spin distribution in triplet 2-chloro-4-
nitroanisole by Hartree-Fock calculation using a 3-21G* basis set.
If σ-complex formation occurs within the triplet manifold,
the reaction is an internal conversion process, but application
of the energy gap law to this case predicts the wrong
product since triplet meta σ-complexes appear to be much
lower in energy than triplet para σ-complexes.12 Moreover,
application of the energy gap law would require intersystem
crossing to be concerted with conversion from the triplet
encounter complex to a singlet σ-complex. A further indication
that this is not the mechanism may be seen from the absence
of a spin-orbit coupling effect on the rates. We see relative
rates of bond formation at the halogen-bearing carbon
for F/Cl/Br/I of roughly 30:2:2:1. Since spin-orbit coupling is
essential to rapid intersystem crossing, the relative rates
should lie strongly in the opposite direction if intersystem
crossing were involved because I . Br > Cl > F in spin-
orbit coupling. These considerations seem to us to settle the
question in favor of nucleophilic reaction occurring within the
triplet manifold.
Certain details of the formulation of this model lead us to
question its applicability to the reactions reported here. The
energy gap law applies most strongly to internal conversion
processes in which the states have the same multiplicity, which
is not the case here. Moreover, the states involved in an
electronic internal conversion that might be energy gap con-
trolled must be of sufficiently similar geometries that their
electronic surface wells align with each other and do not have
a surface intersection at low energy levels of the lower state. If
they are offset, a surface crossing can occur at easily accessible
vibrational levels that would sidestep low probability, energy-
forbidden processes. Offset of energy wells seems likely to be
the case for the reactions reported here because the geometries
of the upper and lower states differ substantially. Moreover,
the suggestion12 that the energies of the triplet σ-complexes,
whose energies were estimated by CNDO/2 calculations, should
represent the energies of the triplet encounter complexes seems
questionable.
The key to understanding the regiochemistry of these reac-
tions may lie in a little noticed result of van Riel, Lodder, and
Havinga,12 namely, that the triplet meta σ-complexes of
nitrophenyl ethers with methoxide ion or hydroxide ion are
about 14 kcal/mol more stable than the triplet para
σ-complexes, as indicated by CNDO/2 calculations. While we
do not know at this time the energy of the triplet aromatic-
nucleophile encounter complex, the result implies that conver-
sion from a triplet aromatic-nucleophile encounter complex
to a triplet σ-complex may be more endothermic or less
exothermic for a para σ-complex than for a meta σ-complex. A
suggestion of why this might be so is indicated in Figure 4,
which shows that the odd electrons in the triplet of 2-chloro-
4-nitroanisole are distributed in the ring entirely at C1, C3,
and C5, and not at all at C2, C4, and C6, the positions most
susceptible to nucleophilic attack. Very similar results for the
odd electron distribution were obtained for all of the triplet
nitroanisoles in this study, whether the calculations were
done by semiempirical methods (MINDO, AM1, or PM3) or
by higher order calculations (Hartree-Fock with 3-21G*
or 6-31G* basis sets, or by density functional methods).
Inasmuch as the triplet π,π* state can be represented as having
the promoted electron in an antibonding orbital mostly on the
nitro group and the electron hole mostly in the π-orbitals of
the ring (a cation radical moiety), approach of a nucleophile
to bond at C1, C3, or C5 would be unfavorable initially because
We envision nucleophilic attack on the triplet as shown in
Scheme 4. The first structure is a modified valence bond
depiction of the triplet π,π* excited state of a halonitroanisole
showing the promoted electron in an antibonding orbital mainly
on the nitro group and the electron hole mainly in the π-orbitals
of the ring. Electron-paired bond formation occurs within the
triplet manifold. The product triplet σ-complex probably
undergoes spin inversion quite rapidly to make the singlet
σ-complex. This sequence is not quite the same as σ-bonding
by the triplet plus nucleophile entering a funnel in the potential
energy surface leading to the singlet σ-complex, a suggestion
we had made earlier.10 Electron-paired bond formation within
the triplet manifold (that is, with no kinetic involvement of spin
inversion) explains the astounding facts that the photochemical
reactions show small local van der Waals and σ-bond polariza-
tion effects and nucleophilicity effects that are similar to those
of ground state reactions despite being about 1014 times faster.
Reaction within the triplet manifold also explains why there is
no observable spin forbiddenness in the diffusion-controlled
reaction of fluoride 4. The relatively unfavored displacement
of the para methoxy group by hydroxide ion may result from
some small endothermicity, or lower exothermicity, or revers-
ibility that could result from the bond-forming reaction occurring
within the triplet manifold, but this would not be spin forbid-
denness. Electron-paired bonding of an excited triplet molecule
1932 J. Org. Chem., Vol. 73, No. 5, 2008

Nucleophilic Aromatic Photosubstitution
of 5 with NaOH that is typical of those used for NMR product
analyses of the hydroxide ion reactions is in the Supporting
Information.
to a nucleophile appears to be analogous to a recently discovered
electron-paired nucleophilic reaction of a para benzyne biradi-
cal.33
The requisite extinction coefficients at relevant wavelengths in
33% CH3CN-H2O for the UV-vis product analyses of photolyses
of 4-7 with NaOH are in Table 3. The spectrum of each
photoproduct mixture was analyzed at completion of photolysis,
which was done with chromate-filtered light (313 nm) from broad-
band 300 nm lamps in 1.0 cm cuvettes. Completion was determined
by UV/vis spectral overlays for reactions at 1.0 × 10-4 M starting
material and 0.010 M NaOH. The reactions all showed sharp
isosbestic points and were analyzed by iteration for composition
of the three types of products at wavelengths of 405, 323, and 265
nm assuming that the sum of the concentrations was 1.0 × 10-4
M. The small extinctions of sodium 4-methoxyphenoxide were
taken to represent those of the sodium 3-halo-4-methoxyphenoxides
and their unknown photohydrolysis products. Because the extinc-
tions are small, the method essentially estimates the yields of 3-halo-
4-methoxyphenoxides by difference based on the more intensely
absorbing nitrophenoxides.
Photolyses for NMR analyses of products were carried out in
borosilicate NMR tubes with unfiltered radiation from 300 nm
broad-band lamps (Rayonet RPR-208) with starting material
concentrations of about 0.005 M and nucleophile concentrations
of about 0.01 M. Solutions were not freed of oxygen except for
the cyanide ion cases, which were bubbled out with argon.
Photolyses for determination of quantum yields were carried out
in 1.0 cm septum-closed quartz cuvettes with starting materials at
2.2 × 10-4 M in 33% CH3CN-H2O. Solutions were freed of
oxygen by bubbling with argon. The concentration of NaCN ranged
from 0.020 to 0.0010 M; that of NaOH was 0.010 to 0.0010 M;
and that of pyridine was 0.040 to 0.0020 M. The concentration of
cyanide ion was corrected for hydrolysis as if it were in pure water.
Irradiation at 313 nm was carried out in the Rayonet chamber with
300 nm lamps by suspending the cuvette in a quartz well containing
approximately a 1 cm path on all sides of aqueous 0.002 M K2-
CrO4 containing 5% Na2CO3. The samples were approximately
optically opaque at 313 nm. Reactions were followed to completion
by making spectral overlays (200-600 nm) for reaction at an
intermediate nucleophile concentration to find an appropriate
wavelength for quantitative analysis. The reactions were clean as
judged by sharp isosbestic points. The progress was linear with
time of irradiation through at least 10% reaction, and they were
analyzed between 5 and 10% of completion. The actinometer was
azoxybenzene in ethanol,25 and typical absorbed light intensity was
2.87 × 10-6 einsteins/L/s.
Experimental Section
The 2-halo-4-nitroanisole photoreactants were prepared from the
available 2-haloanisoles by nitration in 1:1 HNO3(70%)/HOAc by
the method of Reverdin.34 2-Methoxy-5-nitrobenzonitrile was
prepared similarly. After recrystallization from ethanol-water, the
melting points of these substances agreed with the literature values,35
and they gave satisfactory 1H NMR spectra. 4-Nitroanisole,
4-methoxyphenol, 4-nitrophenol, 4-methoxybenzonitrile, 2-meth-
oxy-5-nitrophenol, 3-bromo-4-methoxybenzonitrile, and 3-chloro-
4-methoxybenzonitrile were commercial substances whose 1H NMR
spectra matched those of any corresponding photoproducts. The
pyridinium salt from 1 has been reported,23 as has that from 6.24
We confirmed the pyridinium salts from 4-7 principally from the
coincidence of the UV/vis spectra of our photoreactions at comple-
tion (λmax ) 300 nm, ꢀ ) 10 900 in 33% acetonitrile/water) with
the spectrum reported24 (λmax ) 301 nm, ꢀ ) 12 000 in 10% t-butyl
alcohol/water). We also confirmed the pyridinium salt from 1 and
that from 6 by their NMR spectra, which were as expected. The
3-halo-4-methoxybenzonitriles that are minor products from the
1
cyanide ion photoreactions were identified in solution by their H
NMR spectra, which were similar to each other and were as
expected. The chloride and bromide were confirmed directly with
authentic samples. The nitronate ion photoproduct that is the major
product from 1 with cyanide ion was identified by NMR and by
oxidation with 3,5-dinitrobenzoic acid, as described in Results. The
nitronate ions that are minor products from the cyanide ion
photoreactions with 4-7 were identified in solution also by their
1H NMR spectra, especially the upfield-shifted methoxy signal. One
of these, formed in low yield from chloride 5, was confirmed by
oxidizing the photoproducts in solution in an NMR tube with 3,5-
dinitrobenzoic acid, which caused replacement of the nitronate ion
peaks with those assignable to the aromatized substance, 3-chloro-
2-methoxy-5-nitrobenzonitrile. An example of a 1H NMR spectrum
used for product analysis of the photoreaction of 5 with cyanide
ion is included in the Supporting Information.
The minor products from the hydroxide ion photoreactions
include the 2-halo-4-nitrophenols and the 3-halo-4-methoxyphenols.
The former were characterized by NMR and UV/vis. Samples of
4-7 (0.010 M) and NaOD (0.10 M) in 25% DMSO-d6/D2O were
heated in NMR tubes at 80 °C, and the thermal hydrolysis of the
methoxy group, as shown by quantitative production of methanol,
was followed in each case by periodic observation of the spectrum.
The reactions were clean with half-lives on the order of 10 h. The
2-halo-4-nitrophenol anion was the other product in each case. Each
of these gave the expected NMR spectrum, with the exception that
substantial or complete deuterium exchange occurred at C-3. The
product solutions at completion were diluted quantitatively in 33%
CH3CN-H2O to obtain the UV/vis spectra of the anions, all of
which showed the expected λmax near 400 nm, ꢀ ) ca. 19 000 (see
below).
Nanosecond transient absorption spectroscopy was carried out
with samples in oxygen-free 33% CH3CN-H2O in 1.0 cm quartz
cuvettes. Samples of 1 and 4-7 with an optical density of about
0.5 at 355 nm were excited with 8 ns, 2.8 mJ, 355 nm pulses from
frequency-tripled output of a Nd:YAG laser. The excitation pulse
was directed to a 5 mm diameter spot matched collinearly to the
probe pulse from a xenon flashlamp. The probe pulse was detected
by passing it through a monochromator to a photomultiplier tube
whose output terminated in a fast storage oscilloscope. About 100-
150 kinetic traces taken over several minutes were averaged at each
of 4-6 wavelengths between 390 and 415 nm to determine the
wavelength maximum of the transient and its decay kinetics. The
spectra are attributable to a triplet-triplet absorption. Analysis of
the kinetic data was performed with a Levenberg-Marquardt
nonlinear least-squares fit to a general sum-of-exponentials function
with an added Gaussian to account for the instrument response time
of about 8 ns. Determination of the maximum optical density of
the transient was done manually by inspecting the OD versus time
output at each of the wavelengths investigated. The triplet lifetime
in each case is an average of 4-9 determinations, each representing
an average of 100-150 kinetic traces.
3-Bromo-4-methoxyphenol and its sodium salt were prepared
in solution by adding bromine to 4-acetoxyanisole followed by
alkaline hydrolysis of the ester. The NMR spectra were as
expected. That of the anion matched the NMR spectrum of one of
the minor products of the photolysis of 6 with NaOH and closely
matched the NMR spectra of the other 3-halo-4-methoxyphenoxides
that are minor products of the photolyses of 4, 5, and 7. An
NMR spectrum of a photoproduct mixture from the photolysis
(33) Perrin, C. L.; Rodgers, B. L.; O’Connor, J. M. J. Am. Chem. Soc.
2007, 129, 4795.
(34) Reverdin, F. Chem. Ber. 1896, 29, 2598.
(35) Dictionary of Organic Compounds; Pollock, J. R. A., Stevens, R.,
Eds.; Oxford: New York, 1965; Vols. 1-3.
Molecular orbital calculations were carried out with Spartan ’04,
version 1.0.3, software running on a desktop computer. Semiem-
J. Org. Chem, Vol. 73, No. 5, 2008 1933

Wubbels et al.
pirical AM1 calculations were used for most cases, but higher level
calculations of Hartree-Fock or density functional type with
3-21G* or 6-31G* basis sets were used to check on the accuracy
of the AM1 calculations.
ki of Northwestern University for the transient measurements.
We thank Dr. Albert Stolow for a discussion of the energy gap
law.
Supporting Information Available: 1H NMR spectrum sup-
porting Scheme 1, typical 1H NMR spectra for product analyses of
NaCN, NaOH, and pyridine photoreactions, a typical transient decay
curve, and calculated details for Figure 4. This material is available
free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. This paper is dedicated to Joseph F.
Bunnett on the occasion of his 86th birthday. Acknowledgement
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 Wasielews-
JO702468D
1934 J. Org. Chem., Vol. 73, No. 5, 2008