A meta effect in organic photochemistry? The case of SN1 reactions in methoxyphenyl derivatives

Article abstract of DOI:10.1021/ja068647s

The photochemistry of isomeric methoxyphenyl chlorides and phosphates has been examined in different solvents (and in the presence of benzene) and found to involve the triplet state. With the chlorides, C-Cl bond homolysis occurs in cyclohexane and is superseded by heterolysis in polar media, while the phosphate group is detached (heterolytically) only in polar solvents. Under such conditions, the isomeric triplet methoxyphenyl cations are the first formed intermediates from both precursors, but intersystem crossing (isc) to the singlets can take place. Solvent addition (forming the acetanilide in MeCN, the ethers in alcohols, overall a S_N1 solvolysis) is a diagnostic reaction for the singlet cation, as reduction and trapping by benzene are for the corresponding triplet. Solvolysis is most important with the meta isomer, for which the singlet is calculated (UB3LYP/6-31g(d)) to be the ground state of the cation (ΔE = 4 kcal/mol) and isc is efficient (k_isc ca. 1 × 10⁸ s^-1), and occurs to some extent with the para isomer (isoenergetic spin states, fee ca. 1.7 × 10⁶ s ^-1). The triplet is the ground state with the ortho isomer, and in that case isc does not compete, although trapping by benzene is slow because of the hindering of C₁ by the substituent. The position of the substituent thus determines the energetic order of the cation spin states, in particular through the selective stabilization of the singlet by the m-methoxy group, a novel case of "meta effect".

Full text of DOI:10.1021/ja068647s

Published on Web 04/04/2007
A Meta Effect in Organic Photochemistry? The Case of S
N
1
Reactions in Methoxyphenyl Derivatives
Valentina Dichiarante, Daniele Dondi, Stefano Protti, Maurizio Fagnoni, and
Angelo Albini*
Contribution from the Department of Organic Chemistry, UniVersity of PaVia, V. Taramelli 10,
7100 PaVia, Italy
2
Received December 2, 2006; E-mail: angelo.albini@unipv.it
Abstract: The photochemistry of isomeric methoxyphenyl chlorides and phosphates has been examined
in different solvents (and in the presence of benzene) and found to involve the triplet state. With the chlorides,
C-Cl bond homolysis occurs in cyclohexane and is superseded by heterolysis in polar media, while the
phosphate group is detached (heterolytically) only in polar solvents. Under such conditions, the isomeric
triplet methoxyphenyl cations are the first formed intermediates from both precursors, but intersystem
crossing (isc) to the singlets can take place. Solvent addition (forming the acetanilide in MeCN, the ethers
N
in alcohols, overall a S 1 solvolysis) is a diagnostic reaction for the singlet cation, as reduction and trapping
by benzene are for the corresponding triplet. Solvolysis is most important with the meta isomer, for which
the singlet is calculated (UB3LYP/6-31g(d)) to be the ground state of the cation (∆E ) 4 kcal/mol) and isc
8
-1
is efficient (kisc ca. 1 × 10 s ), and occurs to some extent with the para isomer (isoenergetic spin states,
6
-1
k
isc ca. 1.7 × 10 s ). The triplet is the ground state with the ortho isomer, and in that case isc does not
compete, although trapping by benzene is slow because of the hindering of C by the substituent. The
1
position of the substituent thus determines the energetic order of the cation spin states, in particular through
the selective stabilization of the singlet by the m-methoxy group, a novel case of “meta effect”.
Nucleophilic substitution reactions have had an important role
in the development of organic photochemistry. In 1956 Havinga
reported that the hydrolysis of nitrophenyl phosphates and
sulfates, not occurring to a significant extent at room temper-
ature, was much accelerated by (room) light and actually
occurred smoothly by deliberate irradiation, in particular in the
proposal)5a,b and found that the electron density was transmitted
to and from the meta (and ortho) position, rather than to the
para and ortho position as in the ground state. The phenomenon
was termed the “meta effect”.
Along with other typical thermal/photochemical dichotomies,
such as the opposite stereochemistry in electrocyclic reactions,
this was one of the key observations evidencing the different
1
case of the meta isomers (see Scheme 1a). The reaction was
5
c-e
behavior of excited states versus ground states
and gave
later characterized as a SN2 (Ar*) process and it was demon-
strated that the process mainly involved cleavage of the C-O
bond under basic conditions or of the P-O bond in a neutral
impetus to the development of organic photochemistry and its
rationalization in the following years. Subsequent studies have
2
solution.2,3 In 1963, Zimmerman reported a new example of
afforded further examples of this directing effect, and ratio-
nalizations based on the charge distribution have again been
the meta effect by electron-withdrawing groups in aryl trityl
ethers and further that hydrolysis of benzyl acetates was
6
found useful. However, recognizing an effect of the excited-
state structure on the rate of reaction requires that this term be
disentangled from the many factors contributing to the overall
photochemical reactivity (singlet or triplet reaction, competing
radiative and nonradiative decays, reversibility of the reaction,
identification of the step of the mechanism where the substituent
exerts its effect), as shown, for example, for the photo-Claisen
reaction of aryl allyl ethers by Pincock through a thorough
accelerated by electron donor groups positioned meta to the site
involved (Scheme 1b).4 The latter author rationalized the
observed effect on the basis of the calculated charge distribution
in the excited states (by the H u¨ ckel method, but the result did
not change when using CASSF computations, as in a new
(
1) Havinga, E.; de Jongh, R. O.; Dorst, W. Recl. TraV. Chim. Pays-Bas 1956,
5, 378.
7
7
study. While one has to be aware of this difficulty, the didactic
(
2) Havinga, E.; Cornelisse, J. Chem. ReV. 1975, 75, 353. Cornelisse, J. In
Handbook of Organic Photochemistry and Photobiology; Horspool, W. H.;
Song, P. S., Eds.; CRC Press: Orlando, 1995; p 250-265. Karapire, C.;
Icli, S. In Handbook of Organic Photochemistry and Photobiology, 2nd
ed.; Horspool, W. H.; Lenci, F., Eds.; CRC Press: Orlando, 2004; Section
(5) (a) Zimmerman, H. E. J. Phys. Chem. A 1998, 102, 5616. (b) Zimmerman,
H. E. J. Am. Chem. Soc. 1995, 117, 8988. (c) Zimmerman, H. E. AdV.
Photochem. 1963, 1, 183. (d) Zimmerman, H. E.; Schuster, D. I. J. Am.
Chem. Soc. 1962, 84, 4527. (e) Zimmerman, H. E. Pure Appl. Chem. 2006,
78, 2193.
(6) Epiotis, N. D.; Shaik, S. J. Am. Chem. Soc. 1978, 100, 29. Mutai, K.;
Nakagaki, R.; Tukada, H. Bull. Chem. Soc. Jpn. 1985, 58, 2066. Mutai,
K.; Nakagaki, R. Bull. Chem. Soc. Jpn. 1985, 58, 3663.
(7) (a) Pincock, J. A. Acc. Chem. Res. 1997, 30, 43. (b) Pincock, A. L.; Pincock,
J. A.; Stefanova, R. J. Am. Chem. Soc. 2002, 124, 9768.
37. Cantos, A.; Marquet, J.; Moreno-Ma nˇ as, M. Tetrahedron 1987, 43,
51. Fagnoni, M.; Albini, A. Mol. Supramol. Photochem. 2006, 14, 131.
3
(
3) de Jongh, R. O.; Havinga, E. Recl. TraV. Chim. Pays-Bas 1968, 87, 1318.
de Jongh, R. O.; Havinga, E. Recl. TraV. Chim. Pays-Bas 1968, 87, 1327.
4) Zimmerman, H. E.; Sandel, V. R. J. Am. Chem. Soc. 1963, 85, 915.
Zimmerman, H. E.; Somasekhara, S. J. Am. Chem. Soc. 1963, 85, 922.
(
10.1021/ja068647s CCC: $37.00 © 2007 American Chemical Society
J. AM. CHEM. SOC. 2007, 129, 5605-5611
9
5605

A R T I C L E S
Dichiarante et al.
Scheme 2. Products from the Photolysis of Isomeric
Scheme 1. SN2 and SN1 Paths in Photonucleophilic Substitution
Methoxyphenyl Chlorides and Phosphates
Results
In the following, we report a study of the photochemistry of
the three chloroanisoles (1a-3a) in various solvents, both neat
and in the presence of benzene as a typical π trap for
electrophiles. This was supplemented by a parallel study on the
corresponding methoxyphenyl phosphates (1b-3b), since some
phenyl phosphates bearing a methoxy or dialkylamino group
in 4 (as well as the corresponding mesylates and triflate) had
been shown to give the same trapping products as the chlo-
1
0
rides. Thus, comparison of the two series of aromatics with
different (potential) nucleofugal groups may offer a test for the
involvement of a common intermediate and reveal the effect of
substituents both on the formation and on the reactivity of such
intermediate, if any. The experimental work was complemented
by DFT calculations as a support to the mechanistic proposal.
Photochemistry. The photochemistry of the above aromatics
was investigated in a series of solvents, from nonpolar to highly
polar. Irradiation at 254 nm of 2-chloroanisole (1a) gave only
anisole (4) in all of the solvents tested, namely, cyclohexane,
acetonitrile, methanol, and 2,2,2-trifluoroethanol (TFE) (see
Scheme 2). The highest quantum yield of reaction measured
was in cyclohexane (0.33), while the value in MeCN was 40
times smaller and intermediate values were observed in the
alcohols (Table 1). Reduction to 4 was again the only photo-
process from 3-chloroanisole (2a) in cyclohexane, but this was
not the case in the other solvents. Thus, in MeCN compound 4
was accompanied by N-(3-methoxyphenyl)-acetanilide (5), that
is, a product resulting from chlorine substitution by the weakly
nucleophilic N atom of the solvent (see Scheme 2). Similarly,
in the alcohols the corresponding ethers 6 and 7 were formed;
indeed, the ether was the main product in TFE. A similar course
was followed in part with 4-chloroanisole (3a), with which
reduced 4 was the only product in both cyclohexane and MeCN
but was accompanied by the ethers 8 and 9 in the alcohols (in
TFE also by 4-fluoroanisole, 10), although in a lower proportion
than with 2a. With both 2a and 3a, the quantum yield strongly
decreased from cyclohexane to MeCN and grew again in the
alcohols.
value of such simple rationalizations makes it desirable that more
examples of directing effect are found.
Recalling that electron-donating meta substituents had been
found to accelerate photosolvolyses at the benzylic position in
the original study, we wondered whether a donating group may
4
direct the substitution at a phenylic position, obviously in a
reaction the mechanism of which could be well understood. As
an example, a donating group may favor photosubstitution via
a SN1 mechanism, in contrast to the favored SN2 path with
electron accepting substituents (see Scheme 1c). However, there
are only a few examples of the former mechanism in the
literature2 and no indication about the directing effect of
substituents on it. The photosolvolysis of isomeric chloroanisoles
could be an obvious choice for investigating this point. The
photochemistry of these compounds has been investigated, and
reduction and substitution of the chloro atom have been
observed. However, it has been concluded that the three isomers
were best discussed separately, and there was no common
mechanism.8
In contrast, it was recently shown that irradiation of 4-chlo-
roaniline, -anisole, and -phenol in the presence of π nucleophiles
supported that unimolecular heterolysis of the C-Cl bond
9
occurred giving the corresponding phenyl cations. These
intermediates underwent electrophilic attack either to the solvent
(resulting in overall solvolysis of the aryl chloride) or to the
π-nucleophile (giving the respective arylated products). We
reasoned that comparing the two reactions as well as the key
photophysical parameters and the medium effect on them may
offer a handle for understanding the mechanism and the possible
existence of a directing effect by the substituent on some
intermediate.
(
8) Siegman, J. R.; Houser, J. J. J. Org. Chem. 1982, 47, 2773 and references
cited therein.
(9) Fagnoni, M.; Albini, A. Acc. Chem. Res. 2005, 39, 713.
(
10) De Carolis, M.; Protti, S.; Fagnoni, M.; Albini, A. Angew. Chem., Int. Ed.
2005, 44, 1232.
5606 J. AM. CHEM. SOC.
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VOL. 129, NO. 17, 2007

S
N
1 Reactions in Methoxyphenyl Derivatives
A R T I C L E S
Table 1. Quantum Yield of Reaction and Product Formation for
the Photochemical Reaction of o-, m-, and p-chloroanisole
As it appears from Figure 1, a linear correlation was obtained
when plotting the reciprocal of the ratio between the yield of
biphenyl and the yield of the other photoproducts versus that
of benzene concentration. The slope was 6.4 for 1a, 1.06 for
(
1a-3a) and Methoxyphenyl Diethyl Phosphates (1b-3b) in
Various Solvents
Products formed and quantum yields
from the photolysis of anisoles 1-3
2
a, and 67.7 for 3a.
solvent
1a
2a
3a
Photophysical Data. Some photophysical parameters were
determined. Chlorides 1a-3a were barely fluorescent, while
the fluorescence from phosphates 1b-3b reached a yield of
some percents, with a lifetime of about 1 ns and minimal
dependence on the solvent characteristics (Table 3). On the other
hand, all of the above compounds except 1a exhibited intense
phosphorescence in EPA glass. Flash photolysis experiments
showed no signal attributable to the triplet states in polar
solvents.
C6H12
MeCN
MeOH
CF3CH2OH
4, 0.33
4, 0.008
4, 0.08
4, 0.012
4, 0.28
4, 0.13
4, 0.003
4, 0.08; 8, 0.02
4, 0.03; 9, 0.02; 10, 0.02
4, 0.01; 5, 0.01
4, 0.12; 6, 0.08
4, 0.05; 7, 0.08
solvent
1b
2b
3b
C6H12
MeCN
MeOH
4, 0.013
4, 0.012
4, 0.011
4, 0.009
4, 0.026
4, 0.0012
4, 0.0017
4, 0.10; 8, 0.06
4, 0.036
a
CF3CH2OH 4, 0.028
4, 0.008, 7, 0.056 4, 0.09: 9, 0.06; 10, 0.13
Calculations. To test the viability of heterolytic fragmentation
of the aryl-heteroatom bond as the initiating step, a series of
calculations were carried out by a DFT approach, which has
been shown to be well suited to characterize ionic mechanism.
B3LYP(6-31G(d)) calculations were carried out for the three
methoxyphenyl cations 15-17 in the gas phase and in MeCN
a
A further portion of 1b reacted to give 2-methoxyphenol 11 (about 2/3
of 4) via thermal hydrolysis, as checked by blank experiments.
Scheme 3. Products from the Photolysis of Isomeric
Methoxyphenyl Chlorides and Phosphates in the Presence of
Benzene
1
2
bulk by the CPCM method. For the 2- and 3-substituted
isomers, two low-lying structures were located, according to
the orientation of the methoxy group, away from or toward the
divalent carbon (see later). The key features resulting from the
calculations can be summarized as follows.
First, the structure of these ions was scarcely affected by the
relative position of the substituent and divalent carbon, while
it was quite different according to multiplicity. Thus, triplet
Examination of the three methoxyphenyl phosphates showed
that the product distribution was similar, with 1b giving only
, and 2b and 3b giving also the ethers 6-9 in the alcohols (as
well as the fluoride 10 from 3b in TFE). Differently from the
previous series, however, the quantum yield remained low (some
percent) along the sequence of solvents, though regularly
increasing with polarity. This trend was more dramatic with
3
3
cations 15- 17 were all planar, with a geometry close to a
1
1
regular hexagon, while in the singlets 15- 17 a puckering of
the ring and a small out of plane displacement were observed
at C1 (C2-C1-C6 angle, 143.5, 146.0, 146.4° in the three
isomers, dihedral angle at C1, e5°) (see Table 4 and Figure 2).
4
3
(
2
b, where it increased by a factor of >200 from 0.0012
cyclohexane) to 0.28 (TFE). In TFE a certain amount of
-methoxyphenol (11) was formed from 1b, but this was due
to thermal solvolysis of the phosphate ester moiety.
Preparative irradiations were performed also under acetone
sensitization (by using “310 nm” phosphor-coated lamps in the
presence of 0.9 M acetone, which absorbed most of the light
under these conditions) and were found to give the same product
distribution.
Trapping Experiments. A product study was then carried
out in the presence of 1 M benzene and using acetone as the
sensitizer. Under these conditions, biphenyls 12-14 were
formed competitively at the expenses of anisole. In all of the
cases, the amount of biphenyls increased with the solvent
polarity, but to a different extent. Thus, 14 was the only product
from both 3a and 3b in TFE, whereas with the ortho and meta
chlorides and phosphates, the biphenyl reached a 40-50% yield
in that solvent (Table 2). Direct and sensitized irradiation gave
essentially the same product distribution, as it was demonstrated
in the case of 3a, which absorbed a sufficient part of the light
The energies of the isomeric cations are also reported in the
Table (relative to 15′), where it appears that there was little
difference among the triplets, whereas the meta isomer was
markedly stabilized among the singlets. In particular, the ortho
and meta isomers having the methoxy group pointing toward
C1 enjoyed some extra stabilization (compare 15′ and 16′ with
15 and 16). With 15′ this amounted to 2.2 kcal/mol and involved
from the 310 nm lamps for making direct irradiation in the
presence of benzene feasible11 (see Scheme 3 and Table 2).
The dependence of the yield of trapping products 12-14 on
benzene concentration was explored under sensitized conditions.
a stabilizing interaction between methyl hydrogens and the
divalent carbon. As for the relative order of the spin states, with
the ortho isomer the triplet was the lowest state (by 2.5-4 kcal/
mol in MeCN bulk, depending on the conformer), while with
(
11) The other chloroanisoles and the phosphates had a somewhat blue-shifted
absorption and did not react conveniently with 310 nm lamps.
(12) See Supporting Information.
J. AM. CHEM. SOC.
9
VOL. 129, NO. 17, 2007 5607

A R T I C L E S
Dichiarante et al.
Table 2. Products from the Sensitized (0.9 M Acetone) Irradiation of o-, m-, and p-chloroanisole (1a-3a) and Methoxyphenyl Diethyl
Phosphates (1b-3b) in the Presence of 1 M Benzene (in italic, Yields from the Nonsensitized Irradiation)
products formed (% yield)
solvent
1a
2a
3a
MeCN
MeOH
CF3CH2OH
4 (17), 12 (20)
4 (65), 12 (16)
4 (11), 12 (45)
4 (18), 5 (7), 13 (36)
4 (20), 6 (44), 13 (18)
4 (4), 7 (43), 13 (51)
4 (79, 79), 14 (18, 9)
4 (20, 40), 8 (7, 8), 14 (71, 27)
14 (100, 100)
solvent
1b
2b
3b
MeCN
MeOH
CF3CH2OH
4 (25), 12(30)
4 (28), 12 (5)
4 (36), 12 (15), 11 (40)
13 (11)
13 (7)
7 (25), 13 (34)
14 (65)
14 (10)
14 (96)
Figure 1. Ratio between the yield of biphenyls 12-14 and that of the
other products from chloroanisoles 1a (2), 2a (9), 3a (b) vs the benzene
concentration.
Table 3. Some Key Photophysical Parameters for Methoxyphenyl
Chlorides and Phosphates
a
fluo, nsa
E
T
, kcal/ molb
Φ
fluo
τ
Figure 2. Bond lengths (Å), angles (∠ , in deg), and dihedral angles (∠ , in
1
,3
2
3
1
2
3
a
a
b
b
b
0.0003
80
80
81
82
81
deg) for triplet and singlet 4-methoxyphenyl cation 17 and for the two
3
3
0.021, 0.019
0.045, 0.012
0.040, 0.022
0.033, 0.042
1.55, 1.41
2.04, 1.66
2.46, 2.32
1.92, 1.90
conformers of the triplet 2-methoxyphenyl cation 15 and 15′ as obtained
by B3LYP/6-31G(d) calculations in MeCN bulk.
3
3
Table 5. Triplet o-, m-, and p-cloroanisoles ( 1- 3). Calculated (in
MeCN Bulk) Angles and Dihedral Angles at C1, C1-Cl Distance
[d(C1-Cl)], ESP Charges at the Chloro Atoms [Q(Cl)], and at C1
[Q(C1)], and Energy Difference between the Conformers (∆Econf)
a
In methanol, in italic in cyclohexane; the values in acetonitrile are
intermediate. From the phosphorescence in ethyl ether/pentane/ethyl
alcohol at 77 K.
b
C
2
C
1
C
6
C
1
C
2
C
3
C
4
d(C
1
−
Cl)
∆E
conf
kcal/mola
deg
deg
Å
Q(Cl)
Q(C
1
)
Table 4. o-, m-, and p-Methoxyphenyl Cations (15-17):
3
3
3
Calculated (in MeCN Bulk) Angles and Dihedral Angles at C1 and
Relative Energies with Respect to the Lowest Isomer of Each
Multiplicity (∆E), to the Lowest Conformer of Each Isomer (∆Econf)
and Singlet/Triplet Energy Difference (∆EST) for Each Species
1a
1a′
2a
121.71
122.157
126.51
127.21
122.55
4.74
3.39
-1.981
-1.58
4.72
2.37
2.48
3.15
-0.567
-0.581
-0.569
-0.574
-0.615
-0.02
0.023
0.004
0.017
0.022
3
.9
.3
b
1
32a′
3.10c
3
3a
2.45
C
6
C
1
C
2
C
1
C
2
C
3
C
4
∆E
∆
E
conf
∆E
ST
a
deg
deg
kcal/mol
kcal/mol
kcal/mol
a
Sum of electronic energy and ZPVE. b The chlorine atom displaced at
3
3
3
3
3
1
1
1
1
1
2.60 Å from C4. c The chlorine atom displaced at 2.60 Å from C4.
1
1
1
1
1
1
1
1
1
1
5
5′
6
6′
7
5
5′
6
6′
7
125.35
124.59
126.07
127.32
127.10
146.2
143.5
146.0
146.2
146.4
0.017
+2.2
-2.5
-4.2
5.7
5.5
0.7
2
0
.2
.8
b
-0.004
0.006
0.000
0.000
-0.874
5.48
-5.14
-4.37
0.032
0
the cleavage leading to the cations (vide infra), again using a
DFT approach. The resulting energies are compared in Table
. The lowest energy geometries of some of these states are
+2.1
+1.3
-0.5
+0.4
5
0
0
.4
.6
represented in Figure 3.
c
0
-7.9
-8.5
-5.3
In these states the C-Cl bond was severely stretched and
the chlorine atom was displaced out of the plane, “followed”
by the respective carbon atom, with some loss of skeleton
planarity and a dihedral angle of 2-5°. The C-Cl bond was
weakened and indeed virtually broken both in the gas phase
and MeCN bulk (see the C-Cl distance of ca. 2.4 Å in Table
a
Sum of electronic energy and ZPVE. b Lowest configuration among
the triplets, calcd E) -345.755053 hartree. Lowest configuration among
the singlets, calcd E) -345.748338 hartree (see Supporting Information).
c
5
).
the meta the singlet was stabilized with respect to the triplet by
Further stretching of the bond (by 0.1 Å increments) showed
5
kcal/mol, and in the para the two states were virtually
that only a small energy increase (2-3 kcal/mol) was required
for bringing the chlorine atom to infinity. This process hardly
involved charge separation in the gas phase (charge on the chloro
isoenergetic (a 0.7 kcal/mol difference).
The calculations were extended to the triplet excited states
3
3
3
of chloroanisoles ( 1a- 3a), since these may be involved in
atom equal to ca. -0.2, see the case of 3a in Figure 3b), where
5608 J. AM. CHEM. SOC.
9
VOL. 129, NO. 17, 2007

S
N
1 Reactions in Methoxyphenyl Derivatives
A R T I C L E S
3
•
•
MeOC H Cl f MeOC H + Cl
(1)
6
4
6
4
3
3
This fits with the weakening of this bond in 1a- 3a evidenced
by the present DFT analysis (see Figure 3, d(C1-Cl) ≈ 2.5 Å,
rather than the bonding distance of 1.77 Å). Such cleavage is
6
-1
expected to occur with a rate constant of ca.1 × 10 s , on the
basis of the decay rate of the triplet transient measured by flash
3
15
photolysis for 3a by Lemmetyinnen et al. These authors found
that the triplet was no more observed in MeCN and was
substituted by a transient identified as the chloroanisole radical
•
+
cation 3a , conspicous in water-containing solutions (vide
infra). Apparently, homolysis does not operate in polar solvents,
and the triplet mainly undergoes physical decay rather than
reaction. For the three chloroanisoles the quantum yield of
reaction (Φr) in MeCN drops by a factor of 15-50 with respect
to cyclohexane. On the other hand, Φr increases again by a factor
of 10-30 in going from MeCN to methanol and trifluoroethanol
up to 0.1-0.2. The V-shaped dependence of Φr on the solvent
polarity (or better on the ion stabilizing power) well fits with
the idea that a different (and faster) process sets in under such
conditions, namely, heterolytic cleavage, similarly to what was
Figure 3. (a) Geometries, spin densities, and (in parentheses) ESP charges
3
3
for triplet 4-chloroanisole 3a and 3-chloroanisole 2a from UB3LYP/6-
3
3
1g(d) calculations in MeCN; (b) the same for 3a upon stretching of the
C-Cl bond up to 4 Å in gas phase (left) and in MeCN (right).
the process had a clear homolytic character (0.77 spin on the
Cl atom at 4 Å). On the contrary, in MeCN the process was
3
essentially heterolytic (for 3a the charge at Cl was -0.85).
3
16
A noteworthy characteristic of the 3-methoxy derivative 2a
observed with 4-chloroaniline:
was the displacement of the chlorine atom toward C6. This led
to an interaction with this atom [d(C6-Cl) ) 2.6 Å] that was
stronger that than with C1 [d(C1-Cl) ) 3.1 Å], thus giving some
3
+
-
MeOC H Cl f MeOC H + Cl
(2)
6
4
6
4
3
That photochemistry does not proceed from the singlet state
is indicated by the fact that for the derivatives exhibiting
fluorescence the parameters (ΦF, τF, see Table 3) do not change
significantly in the series of solvents considered, while Φr
changes over 1 or 2 orders of magnitude. With the phosphates
carbene character at C1 and sp character at C6 (see Figure 3a,
the C6-Cl distance was far above the bonding length, though).
3
3
The results with 1a were similar to those with 3a.
With the three chloroanisoles triplets, stretching of the C-Cl
bond was accompanied by return to planarity, and in all of the
cases the positively charged residue had practically the same
geometry as the corresponding triplet phenyl cation.
1
b-3b the fluorescence rate kf () Φf/τf) is also independent
7
-1
of the position of the substituent (kf ) (1.9 ( 0.3) × 10 s )
7
-1
and close to that measured for parent anisole (3 × 10 s ). A
similar value is obtained for 4-chloroanisole 3a (kf ) 1.3 ×
Discussion
7
-1
1
0 s ), while with the two other chlorinated derivatives the
fluorescence is exceedingly weak. Some other decay path thus
operates for 1a and 2a, but this does not hinder the reactions
Photochemical Cleavage. The above data show a varied
photochemical behavior for isomeric methoxyphenyl derivatives
that however can be accounted for by a unitary proposal, as it
will be shown in the following. The photoproduct distribution
indicates a meta effect favoring solvolysis vs reduction. When
the solvent is an alcohol, substitution of the Cl atom by an
alkoxy group was the main process from 2a (e.g., 6/4 ) 1.5 in
MeOH) and also acetonitrile acted as a nucleophile (5/4 ) 1).
On the contrary, substitution had a smaller role with the para
derivative 3a, where reduction predominated (8/4 ) 0.25 in
MeOH), and did not occur at all with ortho 1a (4 was the only
product obtained in this case). Noteworthy, in polar solvents
phosphates, 1b-3b underwent substitution and reduction with
very similar structure/medium dependence, thus supporting that
common intermediates were involved in the photoreactions and
resulted from the loss of either the chloro or phosphate group.
1
1
17a
via the triplet. That isc is efficient with the present compounds,
1
7b
as in general for anisoles, also in polar media is indicated by
the phosphorescence observed in EPA for all of the present
reagents (except 1a), and the viability of the triplet path is
supported by the fact that sensitization by acetone leads in all
of the cases to the same product distribution as direct irradiation.
Homolytic cleavage has no role with the corresponding
arylphosphates, and the quantum yield of reaction of compounds
1
b-3b is at most ca. 0.01 in cyclohexane. The efficiency
consistently grows with polarity, however, in a quite conspicu-
ous way with the para-methoxy derivative 3b, where it varies
from 0.001 in C6H12 to almost 0.3 in TFE.
Role of Phenyl Cations. Calculations show that indeed
cleavage from the triplet chlorides and phosphates is possible
and mimic the twofold reactivity with the results in vacuum,
where the fragmentation is homolytic, and in MeCN bulk, where
it is heterolytic for the three isomeric chloroanisoles considered
It appears that two kinds of photoprocesses are involved. In
apolar media, the only process occurring is reduction, that is
quite efficient with the chlorides 1a-3a and negligible with
the phosphates. This has been previously attributed to C-Cl
homolysis from the triplet state:8
(
15) Lemmetyinnen, H.; Konijnenberg, J.; Cornelisse, J.; Varma, C. A. G. O.
J. Photochem. 1985, 30, 315.
,13,14
(16) Freccero, M.; Fagnoni, M.; Albini, A. J. Am. Chem. Soc. 2003, 125, 1382.
(
17) (a) The occurrence of a further decay from the singlet has been noted also
for 3-fluoroanisole, see ref 7b. (b) The isc is the main path from the singlet
in most anisoles, as observed in several cases, see for example, refs 7, 15,
18, and 19.
(
13) Da Silva, J. P.; Vieira Ferreira, L. F.; Ferreira Machado, I.; Da Silva, A.
M. J. Photochem. Photobiol., A 2006, 182, 88.
(14) Protti, S.; Fagnoni, M.; Mella, M.; Albini, A. J. Org. Chem. 2004, 69,
(18) Den Heijer, J.; Shadid, O. B.; Cornelisse, J.; Havinga, E. Tetrahedron 1977,
33, 779.
3
465.
J. AM. CHEM. SOC.
9
VOL. 129, NO. 17, 2007 5609

A R T I C L E S
Dichiarante et al.
Scheme 4. Trapping of Singlet and Triplet Methoxyphenyl Cation
(
1
see Figure 3). The latter mode of reaction leads to triplet cations
5- 17. The main chemical reaction of such species in solution
3
3
is reduction to anisole via electron and H transfer. Previous
studies with other chlorides, in particular 4-chloroaniline,
suggested that the two steps may occur in either order (Scheme
19
•+
4
, left), namely, either H abstraction to give 4-NH2C6H5 that
Figure 4. Relative energy of singlet and triplet methoxyphenyl cations.
is then reduced or electron transfer from the starting chloro-
•
aniline to give radical 4-NH2-C6H4 and radical cation 4-NH2C6H4-
shown that the minimum energy crossing point of S and T
surfaces of some (4-substituted) phenyl cations is ca. 3 kcal
•+
Cl as the intermediates. Aromatic radical cations are easily
detected by flash photolysis, and previous detection of
-1
21
mol when the two states are isoenergetic, as here with 17,
•
+
•+
15
4
-MeOC6H4Cl (3a ) from 3a supports this mechanism.
while it is negligible when either state is markedly stabilized
Calculations predict a spin-dependent chemistry for phenyl
-1
(
by some kcal mol ). Thus, successful trapping by a large
19a
cations, with the triplets not trapped by n nucleophiles. Triplet
cations rather react with π-nucleophiles, as shown here by the
formation of biphenyls 12-14 from all of the halides and
phosphates in the presence of benzene. On the contrary,
solvolysis to give products 6-9 is attributed to singlet cations
enough benzene concentration shows that 3-methoxyphenyl
cation (16) is initially formed in the triplet state, although in
neat polar solvents, intersystem cross to the singlet (ground)
3
state predominates and leads to solvolysis products. With 17,
isc is slower and competitive reduction in neat solvent and
trapping by benzene have a larger role.
The behavior of the ortho cation 3/115 is somewhat different.
Reduction is virtually the only photoprocess in all of the
solvents. In the presence of benzene, trapping is effective but
never complete, and the slope in Figure 1 is less steep than
with the para isomer. Since the triplet here is markedly below
the singlet, isc to the latter state plays no role, and the low value
of the ktr/(kred + kisc) ratio is attributable to less effective trapping
1
1
19a
1
5- 17, predicted to be unselective electrophiles.
This
process occurs to some extent with the para derivative, and to
a larger one with the meta isomer. Importantly, trapping by
benzene occurs at the expenses both of reduction and of the
substitution products, consistent with the idea that the photo-
chemical reaction yields in all cases the triplet cation and it is
the rate of ensuing isc that then determines the product
distribution (see Scheme 4).
In fact, the singlet state of methoxyphenyl cation is markedly
stabilized with respect to the triplet in the case of meta derivative
(
small ktr). Examination of the structure of the cation evidences
3
that the conformer with the substituent toward C1 ( 15′) is
stabilized with respect to rotamer 15 (by 2.2 kcal/mol, see Table
3/1
3/1
1
6, while the two states are almost isoenergetic with para 17
3
(see Table 4 and Figure 4). Thus, reaction from the triplet cation
4
) because of hydrogen bonding involving the methyl group
competes with isc with meta and, to a degree, with the para
isomer. The more ion stabilizing is the medium, the longer is
the lifetime of the phenyl cation and the higher the probability
of isc. This is indicated by the increasing role of solvolysis
22
(see Figure 2). It is reasonable to expect that hindering by the
substituent makes a reaction with a relatively bulky nucleophile
such as benzene inefficient, so that the rate constant decreases
7
-1 -1
to ktr ≈ 1 × 10 mol s , that is, an order of magnitude lower
(
Scheme 4, right) in the series CH3CN < CH3OH ≈ CF3CH2-
3
than with 17.
OH (apparently following the order of the ion stabilizing factors,
A further aspect of the reactivity of these cations is fluoride
abstraction from TFE to give 10, observed when the 4-substi-
tuted ion 17 is generated from either the chloride or the
phosphate. This reaction has been previously found in the
20
Y ≈ -3.5, -1.09, and 1.045, counterbalanced in the last case
by the poor nucleophilicity).
Competitive Trapping. The plots in Figure 1 give access to
the rate ratios ktr/(kred + kisc). Although phenyl cations have not
been detected by flash photolysis, the rate of addition of
23
decomposition of some phenyldiazonium salts.
S versus T Methoxyphenyl Cations. Calculations show that
4
-alkoxy (or hydroxy) phenyl cation to a π nucleophile (an
3
triplet cations 15-17 differ little in energy, and all have a
8
-1
alkene in water) has been estimated as ktr ≈ 1 × 10 mol
regular hexagonal structure (for details, see Supporting Informa-
-
1 19b
3
3
s . If, as it seem likely, the addition of both 16 and 17 to
benzene occurs at a similar rate, the data in Figure 1 support
that in TFE kisc is 60 times as large with the former cation,
where the process is markedly exothermic, than with the latter
5 1
tion). These intermediates have a π σ structure (see the formula
below), as previously determined for parent triplet phenyl cation
21,22,24
and some 4-substituted derivatives.
As a consequence,
most of the charge is localized not at C1, but on the carbon
8
-1
6
-1 -1
one (1 × 10 s vs 1.7 × 10 mol s ). Aschi et al. have
(21) Aschi, M.; Harvey, J. N. J. Chem. Soc., Perkin Trans. 2 1999, 1059.
(
19) (a) Guizzardi, B.; Mella, M.; Fagnoni, M.; Freccero, M.; Albini, A. J. Org.
Chem. 2001, 66, 6353. (b) Manet, I.; Monti, S.; Fagnoni, M.; Protti, S.;
Albini, A. Chem.sEur. J. 2005, 16, 140.
(22) For an analogous proposal on the stabilization by the methoxy group, see
Filippi, A.; Lilla, G.; Occhiucci, G.; Sparapani, C.; Ursini, O.; Speranza,
M. J. Org. Chem. 1995, 60, 1250.
(20) Winstein, S.; Fainberg, A. H.; Grunwald, E. J. Am. Chem. Soc. 1957, 79,
(23) Canning, P. S. J.; McCrudden, K.; Maskill, H.; Sexton, B. Chem. Commun.
1998, 1971.
4
146; 5937.
5610 J. AM. CHEM. SOC.
9
VOL. 129, NO. 17, 2007

S
N
1 Reactions in Methoxyphenyl Derivatives
A R T I C L E S
Scheme 5. Photochemistry of m-Nitro- vs m-Methoxyphenyl
bearing the methoxy group and on the substituent itself,
independent of their position with respect to the divalent carbon
Phosphate
(
apart from the above-mentioned intramolecular CH3-C1+
interaction in the ortho cation). Thus, the stabilizing effect due
5
to the donation by the methoxy oxygen on the π electron
deficient system is exerted independently from the position,
explaining the fact that the isomeric triplet cations all have the
same energy (within 2 kcal/mol).
compensated for when the donating group is in those positions.
However, both calculations and experiments clearly show that
the meta substituted singlet is selectively stabilized. Thus, one
can label this as a meta effect, although not involving the excited
state, contrary to the cases discussed in the introduction. It is a
peculiar, but coincidental, fact that a meta effect favoring
solvolysis is observed both with m-nitrophenyl phosphate,
On the contrary, a marked positive charge at C1 is apparent
in singlet cations (π σ°), justifying their strong and unselective
6
electrophilic behavior. In these intermediates, the hexagonal
structure is altered, with a puckering of C1. The C2-C1-C6
moiety has some character of a cumulate double bond, and the
C3-C4-C5 moiety has some character of an allylic carbocation.
Therefore, donation from a methoxy group is more effective
when the substituent is in position 3 (see formula 18), as
indicated by the shortening of the C-O bond (1.30 Å in cation
3
because of the activation of the SN2( Ar) due to the enhanced
positive charge at C1 in the triplet of the reagent, and with
m-methoxyphenyl phosphate, where, rather than the initial
1
1
3
1
6, 1.31 in isomeric 17, 1.35 in anisole). This explains the
SN1( Ar) photoreaction, it is the isc of the intermediate cation
1
peculiar stabilization of cation 16 and the reversed S/T energetic
that is affected (see paths 1 and 3 in Scheme 5).
order (Figure 4) with this isomer.
Experimental Section
The photochemical reactions were performed by using nitrogen-
purged solutions in quartz tubes and a multilamp reactor fitted with
six 15 W phosphor coated lamps (maximum of emission 310 nm) for
the irradiation. Chloroanisoles 1a-3a are commercially available and
were distilled before use. Phosphates 1b-3b were obtained from the
10,25
Conclusions. In conclusion, a unitary mechanism is proposed
for the photochemistry of the three chloroanisoles and of the
corresponding phosphates in polar solvents and involves a
heterolytic SN1 path. The efficiency of the photocleavage has
no clear dependence on the substituent position, but there is a
marked meta effect in the chemistry of the key intermediates,
the phenyl cations, in the sense that the m-methoxy substituent
stabilizes the singlet, making it the ground state. Thus, even if
the triplet is formed first, isc is fast and is followed by solvent
addition (resulting in overall solvolysis) with this isomer. This
is an example of the characteristic unselective chemistry of
singlet phenyl cations, which contrasts with the more selective
triplet reactions predominating or exclusive with the other
isomers.
corresponding phenols
A sample of 5 was obtained from the
corresponding aniline through a known procedure.26 Ethers 4, 6, and
8, 10 and phenol 11 were quantified by comparison with commercially
available products. Product 9 was previously isolated and character-
ized.14 The other photoproducts were recognized on the basis of
elemental analysis and spectroscopic characterization. Details are
reported as Supporting Information.
Calculations. Indication of the method used and optimized geom-
etries are reported as Supporting Information.
Acknowledgment. Partial support of this work by MIUR,
Rome, is gratefully acknowledged.
Supporting Information Available: Full experimental details
of photoproducts, optimized geometries listed in Cartesian
format, and energies calculated (B3LYP6-31G(d)) for triplet
chloroanisoles 1a-3a and for singlet and triplet methoxyphenyl
The substituent orientation effect thus operates on the cation
intermediate rather that on the primary photocleavage. Since
electronic effects are transmitted to the ortho and/or para
positions, one may have naively expected that the electron-
withdrawing effect of the charge would have been better
+
+
cations 15 -17 (in gas phase and in MeCN bulk). This
material is available free of charge via the Internet at
http://pubs.acs.org.
JA068647S
(
24) Dill, J. D.; Schleyer, P. v. R.; Binkley, J. S.; Seeger, R.; Pople, J. A.;
Haselbach, E. J. Am. Chem. Soc. 1976, 98, 4528. Nicolaides, A.; Smith,
D. M.; Jensen, M.; Radom, L. J. Am. Chem. Soc. 1997, 119, 8083. Laali,
K. K.; Rasul, G.; Prakash, G. K. S.; Olah, G. A. J. Org. Chem. 2002, 67,
(25) Genkina, G. K.; Shipov, A. E.; Mastryukova, T. A.; Kabachnik, M. I. Russ.
J. Gen. Chem. 1996, 66, 1742.
(26) Akhavan-Tafti, H.; Desilva, R. S.; Arghavani, Z.; Eickholt, R. A.; Handley,
R. S.; Schoenfelner, B. A.; Sugioka, K.; Sugioka, Y.; Schaap, A. P. J.
Org. Chem. 1998, 63, 930.
2
913.
J. AM. CHEM. SOC.
9
VOL. 129, NO. 17, 2007 5611