Photoarylation/alkylation of bromonaphthols

Article abstract of DOI:10.1021/jo802374r

The photochemistry of 6-bromo-2-naphthols has been studied in acetonitrile, aqueous acetonitrile, and isopropyl alcohol in the absence and in the presence of triethylamine by product distribution analysis, laser flash photolysis (LFP), fluorescence, phosp

Full text of DOI:10.1021/jo802374r

Photoarylation/Alkylation of Bromonaphthols
Luca Pretali,† Filippo Doria,† Daniela Verga,† Antonella Profumo,‡ and Mauro Freccero*,†
Dipartimento di Chimica Organica and Dipartimento di Chimica Generale, UniVersita` di PaVia,
27100 PaVia, Italy
mauro.freccero@unipV.it
ReceiVed April 21, 2008
The photochemistry of 6-bromo-2-naphthols has been studied in acetonitrile, aqueous acetonitrile, and
isopropyl alcohol in the absence and in the presence of triethylamine by product distribution analysis,
laser flash photolysis (LFP), fluorescence, phosphorescence, electrochemical measurements, and DFT
calculations. Hydrobromic acid loss in the presence of Et3N occurs from the triplet state of 6-bromo-2-
naphthol, generating an electrophilic carbene intermediate, which has been successfully trapped by oxygen,
allyltrimethylsilane, 2,3-dimethylbut-2-ene, pyrrole, acrylonitrile, 1,4-dimethoxybenzene, and also pyridine.
The generation and the reactivity of a triplet carbene intermediate has been supported by LFP, with the
detection of 2,6-naphthoquinone-O-oxide (530 < λ < 650 nm) in the presence of O2. The electrophilic
diradical character of the carbene has been supported by DFT calculations, using the B3LYP, PBE0, and
MPWB1K functionals, with the 6-31+G(d,p) basis set and PCM solvation model.
Introduction
the resulting radical anion,6 and (iii) heterolysis with the
generation of an aryl cation as intermediate.7
The photochemistry of aromatic halides has been a hot issue
for more than 40 years.1 The carbon-halogen bond cleaving
process, which is triggered by photoexcitation in solution, has
been investigated by product distribution analysis2 and laser flash
photolysis detection (LFP)3 and exploited for both synthetic
purposes2 and mild degradation of organic pollutants in water.4
Mechanistic investigations, which have been stimulated by
environmental issues, identify three main reaction pathways:
(i) homolysis,5 (ii) electron transfer, followed by cleavage of
Ar-X* f Ar• + X•
Ar-X* f (Ar-X)•- f Ar• + X-
Ar-X* f Ar+ + X-
(i)
(ii)
(iii)
More recently, reaction mechanism iii has found synthetic
application by Albini’s group8,9 in the formation of new aryl-
(5) (a) Park, Y.-T.; Song, N. W.; Kim, Y.-H.; Hwang, C.-G.; Kim, S. K.;
Kim, D. J. Am. Chem. Soc. 1996, 118, 11399–11405. (b) Grimshaw, J.; De Silva,
A. P. J. Chem. Soc. 1979, 193–194. (c) Grimshaw, J.; De Silva, A. P. J. Chem.
Soc., Chem. Commun. 1980, 302–303. (d) Grimshaw, J.; De Silva, A. P. Can.
J. Chem. 1980, 58, 1880–1888.
(6) (a) Takeda, N.; Poliakov, P. V.; Cook, A. R.; Miller, J. R. J. Am. Chem.
Soc. 2004, 126, 4301–4309. (b) Costentin, C.; Robert, M.; Save´ant, J.-M. J. Am.
Chem. Soc. 2004, 126, 16051–16057. (c) Chami, Z.; Gareil, M.; Pinson, J.;
Saveant, J.-M.; Thiebault, A. J. Org. Chem. 1991, 56, 586–595. (d) Bunce, N. J.;
Pilon, P.; Ruzo, L. O.; Sturch, D. J. J. Org. Chem. 1976, 41, 3023–3025.
(7) (a) Manet, I.; Monti, S.; Grabner, G.; Protti, S.; Dondi, D.; Dichiarante,
V.; Fagnoni, M.; Albini, A. Chem. Eur. J. 2008, 14, 1029–1039. (b) Dichiarante,
V.; Fagnoni, M.; Mella, M.; Albini, A. Chem. Eur. J. 2006, 12, 3905–3915.
(8) Protti, S.; Fagnoni, M.; Albini, A. Org. Biomol. Chem 2005, 3, 2868–
2871.
† Dipartimento di Chimica Organica.
‡ Dipartimento di Chimica Generale.
(1) Grimshaw, J.; De Silva, A. P. Chem. Soc. ReV. 1981, 10, 181–203.
(2) Protti, S.; Fagnoni, M.; Mella, M.; Albini, A. J. Org. Chem. 2004, 69,
3465–3473.
(3) (a) Grabner, G.; Richard, C.; Ko¨hler, G. J. Am. Chem. Soc. 1994, 116,
11470–11480. (b) Bonnichon, F.; Richard, C.; Grabner, G. Chem. Commun. 2001,
73–74. (c) Bonnichon, F.; Grabner, G.; Guyot, G.; Richard, C. J. Chem. Soc.,
Perkin Trans. 2 1999, 1203–1210. (d) Arnold, B. R.; Scaiano, J. C.; Bucher,
G. F.; Sander, W. J. Org. Chem. 1992, 57, 6469–6474.
(4) Skurlatov, Y. I.; Ernestova, L. S.; Vichutinskaya, E. V.; Samsonov, D. P.;
Semenova, I. V.; Rodko, I. Y.; Shvidky, V. O.; Pervunina, R. I.; Kemp, T. J. J.
Photochem. Photobiol. A 1997, 107, 207–213.
1034 J. Org. Chem. 2009, 74, 1034–1041
10.1021/jo802374r CCC: $40.75 2009 American Chemical Society
Published on Web 01/05/2009

Photoarylation/Alkylation of Bromo-naphthols
SCHEME 1. Photogeneration of 4-Oxocyclohexa-2,5-
dienylidene Carbene (3) and 4-Hydroxyphenyl
Cation (4) from Chlorophenol 1 and Chloroanisole 2
SCHEME 3. Photoreactivity of 6-Br-2-naphthol (5), in the
Presence of Allyltrimethylsilane (X ) TMS), Pyrrole,
2,3-Dimethyl-2-butene, Acrylonitrile, Pyridine, and
1,4-Dimethoxybenzene (X ) H)
SCHEME 2
Results and Discussion
Photoreactivity of 6-Br-2-naphthol: Effects of the Sol-
vents, Oxygen, and Allyltrimethylsilane. The photoreactivity
of 5 was first explored in 2 × 10-3 M solutions using four lamps
(15 W) centered at 310 nm, followed by chromatographic
separation for the structural identification of the products. The
reaction was initially carried out in the presence of allyltrim-
ethylsilane (1-5 × 10-2 M), in several solvents: MeOH,
isopropyl alcohol (IPA), acetonitrile (ACN), and aqueous ACN
(H2O/ACN ) 7:3). In neat ACN and in polar protic solvents
such as MeOH and IPA the reactant was recovered unmodified.
Since allyltrimethylsilane is known to be one of the most
efficient π-nucleophile traps for aryl cation intermediates, its
generation as intermediate was doubtful.14 In preparative
irradiation experiments in argon-flushed aqueous ACN, the main
isolated product was 6-allyl-2-naphthol (9) in fairly good yield
(47%), together with 2-naphthol (10, 15% yield) and unreacted
5 (38%) (Scheme 3). However, in oxygen-equilibrated aqueous
ACN no reactivity was detected. This fact, together with the
evidence discussed in the next chapter, supports the proposal
that reactivity may occur from the triplet excited state of 5 (35*).
In an attempt to buffer the photogenerated acidity (by HBr),
which may induce polymerization, isomerization, or hydrolysis
of electron-rich π-nucleophiles (such as pyrrole and vinyl ethers)
and the resulting adducts, the irradiations were also run in the
presence of Et3N (2 × 10-3 M), in neat and aqueous ACN and
also in IPA. Surprisingly, the addition of Et3N to an ACN
solution of allyltrimethylsilane (2 × 10-2 M) and 5 (2 × 10-3
M) switched on the reactivity with a quantitative conversion of
5 into 9 in higher yield (70% yield) and 10 (30% yield). An
almost identical conversion was achieved also in aqueous ACN
with Et3N. The addition of Et3N to neat IPA afforded a
quantitative conversion to 10 by a clean reductive dehalogena-
tion process. In the presence of allyltrimethylsilane (1-5 × 10-2
M) beside 10 (96%) we also detected 9 in trace amounts (4%
yield, by HPLC). The reaction was also carried out in the
presence of Et3N (6 × 10-3 M) in air-equilibrated neat ACN,
with and without allyltrimethylsilane. In the absence of allyl-
trimethylsilane, 2,6-dihydroxynaphthalene (35% yield) and 10
(22% yield), together with unreacted 5 (25% yield), were
isolated after reductive workup, using Na2S2O4 and column
chromatography separation. In the presence of allyltrimethyl-
silane, under the very same conditions, 2,6-dihydroxynaphtha-
aryl and aryl-alkyl bonds. Among aryl halides, halophenols have
been intensively investigated. In more detail, the photoreactivity
of 4-chlorophenol (1) and derivatives (such as 2) has been
rationalized as the result of a heterolytic process involving
4-oxocyclohexa-2,5-dienylidene carbene (3)3 and 4-hydrox-
yphenyl cation (4) (Scheme 1).2 The carbene 3 arises from a
deprotonation process of the 4-hydroxyphenyl cation, which has
successfully been trapped by several π-nucleophiles, including
allyltrimethylsilane.2 Benzoquinone is the diagnostic trapping
product of the carbene 3, in the presence of oxygen. Despite
the great effort toward mechanistic clarification and synthetic
development related to such a photochemistry, only the reactivity
of 4-chlorophenol (1) and 4-chloroanisole (2) has been thor-
oughly investigated and no reactivity data on halonaphthols are
present, to our knowledge.
The above aspects, conjugated with the current interest of
our group in the photoreactivity of binol-derivatives,10 had
prompted us to explore the photochemistry of several 6-bromo-
2-naphthols and binol analogues. In this work, we describe the
photochemistry of the 6-bromo-2-naphthols 5-8 (Scheme 2)
in the presence of alkenes and aromatics to assess whether the
reactivity of the resulting transient species may be exploited
for the synthesis of functionalized naphthols.
In addition we have undertaken a parallel investigation aimed
to clarify the nature and the properties of the reactive excited
states and the further transients generated upon excitation of
6-bromo-2-naphthols by means of nanosecond laser flash
photolysis (LFP), fluorescence, phosphorescence, and electro-
chemical measurements. The mechanistic aspects of the reaction
have been supported by DFT calculation using the functionals
B3LYP,11 PBE0 (also known as PBE1PBE),12 and MPWB1K13
with 6-31G+(d,p) basis set, coupled with PCM solvation model,
in order to reproduce the acetonitrile solvation effects.
(9) (a) Fagnoni, M.; Albini, A. Acc. Chem. Res. 2005, 38, 713–721. (b) Protti,
S.; Fagnoni, M.; Albini, A. Angew. Chem., Int. Ed. 2005, 44, 5675–5678.
(10) (a) Colloredo-Mels, S.; Doria, F.; Verga, D.; Freccero, M. J. Org. Chem.
2006, 71, 3889–3895. (b) Richter, S. N.; Maggi, S.; Colloredo-Mels, S.; Palumbo,
M.; Freccero, M. J. Am. Chem. Soc. 2004, 126, 13973–13979. (c) Doria, F.;
Richter, S. N.; Nadai, M.; Colloredo-Mels, S.; Mella, M.; Palumbo, M.; Freccero,
M. J. Med. Chem. 2007, 50, 6570–6579.
(11) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 1372–1377. (b) Schmider,
H. L.; Becke, A. D. J. Chem. Phys. 1998, 108, 9624–9631.
(12) (a) Adamo, C.; Barone, V. J. Chem. Phys. 1999, 110, 6158–6170. (b)
Cimino, P.; Gomez-Paloma, L.; Barone, V. J. Org. Chem. 2004, 69, 7414–7422.
(13) Zhao, Y.; Truhlar, D. G. J. Phys. Chem. A 2005, 109, 5656–5667.
(14) (a) Milanesi, S.; Fagnoni, M.; Albini, A. Chem. Commun. 2003, 216–
217. (b) Manet, I.; Monti, S.; Fagnoni, M.; Protti, S.; Albini, A. Chem. Eur. J.
2005, 11, 140–151.
J. Org. Chem. Vol. 74, No. 3, 2009 1035

Pretali et al.
TABLE 1. Product Distribution from the Irradiation (λ ) 310 nm)
of 5 in ACN and Et3N (2 × 10-2 M) in the Presence of Alkenes and
Aromatics
SCHEME 4. Photoreactivity of 8
XYa
conversionb (%)
productsc (% yield)
a
b
c
d
e
f
92
98
100
100
95
10 (32)
11 (83), 10 (4)
10 (92)
9 (70), 10 (30)
12 (38), 10 (40)
13 (16), 10 (10)
14 (30), 10 (2)
14 (92), 10 (-)d
15 (70), 10 (20)
TABLE 2. Product Distribution from the Irradiation of 8 in Neat
Acetonitrile (with Et3N) and in Aqueous Buffered Conditions
90
g
78
productsc
96d
95
XYa
conditions (λ ) 360 nm)b
consumption (%)
(% yield)
h
a
8 + Et3N, CH3CN
75
42
15
90
16 (52), 17 (20)
16 (22), 17 (16)
16 (5), 17 (5)
a Irradiation time 1 h, T ) 30 °C, [5] ) 2 × 10-3 M, [Et3N] ) 2 ×
10-3 M, [NuX] ) 1-5 × 10-2 M; a: morpholine; b: pyrrole; c: EVE;
d: allyltrimethylsilane; e: 2,3-dimethyl-2-butene; f: acrylonitrile; g:
pyridine. h: 1,4-dimethoxybenzene. b Reactant consumption. c The
product yields have been determined after isolation by column
chromatography (cyclohexane/ethyl acetate as eluent) or HPLC
measurements. d Irradiation in neat pyridine in the absence of Et3N.
8 H2O, pH 9.0d
8 H2O/CH3CN ) 1:1, pH 7.8d
8 H2O/CH3CN ) 1:1, pH 9.0d
g
16 (57), 18 (21)
a a: pyrrole; g: pyridine. b Irradiation time 1 h, T ) 30 °C, [8] ) 2 ×
10-3 M, [Et3N] ) 4 × 10-3 M, [NuX] ) 1-5 × 10-2 M. c The product
yields have been determined after isolation by reverse column
chromatography RP C18 (MeOH/H2O ) 1:1 as eluent). d Buffered
conditions.
lene (18% yield), 10 (41% yield), and 9 (19% yield) were
detected by HPLC.
Photoreactivity of 6-Br-2-Naphthol in the Presence of
Alkenes and Aromatics. We next investigated the photoreac-
tivity of the naphthol 5 in ACN solution in the presence of Et3N
(2 × 10-3M) and several traps (XY: n-,π-nucleophiles and
radical traps, 1-5 × 10-2 M) such as morpholine (a), pyrrole
(b), ethyl vinyl ether (c, EVE), allyltrimethylsilane (d), 2,3-
dimethyl-2-butene (e), acrylonitrile (f), pyridine (g), and 1,4-
dimethoxybenzene (h). Naphthol 5 was reductively debromi-
nated to 10 in the presence of morpholine and EVE but was
converted into alkylated/arylated products (Scheme 3) in the
presence of pyrrole, 2,3-dimethyl-2-butene, acrylonitrile, pyri-
dine, and 1,4-dimethoxybenzene, in modest to fairly good yields
(Table 1).
The formation of both the debrominated adduct 10 and the
alkylation/arylation adducts 9, 11, 12, and 15 at first glance
suggests a behavior similar to that of 4-chlorophenol, which
has been demonstrated to give adducts via both the correspond-
ing phenyl cation 4 and carbene 3 in rapid equilibrium.2,3
However, several aspects of this reaction, in particular, (i) the
lack of reactivity in neat MeOH and IPA in the presence of
allyltrimethylsilane, (ii) the reactivity in aqueous ACN and its
quenching by the oxygen, (iii) the reactivity with acrylonitrile
and pyridine, and above all (iv) the key role of Et3N on the
reactivity in neat ACN, suggest a slightly different scenario.
6-Br-2-naphthol Ethers. To understand the role of the phenol-
like proton in the reaction, the photoreactivity of both methyl and
silyl ethers was investigated. 2-Bromo-6-methoxynaphthalene 6 and
(6-bromonaphthalen-2-yloxy)-tert-butyldimethylsilane 7 were cho-
sen. Both 6 and 7 are photostable in MeOH, IPA, and aqueous
ACN, in the presence of allyltrimethylsilane, since the starting
material was quantitatively recovered after 2 h of irradiation. The
lack of reactivity of both 6 and 7, in comparison to that of 5, both
in aqueous ACN and in neat ACN containing Et3N, suggests that
the presence of the free hydroxyl group is mandatory for preserving
the arylation/alkylation reactivity shown by 5. This rules out an
aryl cation as intermediate, since the chemical behavior of both 6
and 7 is very different from that of 4-chloroanisole.7a Such a
conclusion is strengthened by the fact that with 5 alkylation/
arylation occurs, although with a lower yield, also with acrylonitrile
(16% conversion) and pyridine (30% yield in the presence of Et3N;
92% yield in neat pyridine). With these traps, unidentified oligo-
meric byproducts were always recovered. The regiochemistry of
FIGURE 1. Fluorescence emission spectra of 5 and 10 in neat ACN
(a) and in aqueous ACN (b). Excitation wavelength set at 290 nm. (c)
Phosphorescence spectrum of 5 in EPA (diethyl ether/isopentane).
the reaction leading to the adduct 13 was unambiguously estab-
lished by DEPT, NOESY, and HMBC experiments. Arylation of
pyridine at C3 yielding 14 was supported by the pattern of the
1
aromatic protons of the pyridine moiety in the H NMR spectra
and by COSY experiments (see Supporting Information).
Photoreactivity of a Water-Soluble 6-Br-2-naphthol. Ir-
radiation of the naphthalene carboxylic acid 8 at 360 nm in
the presence of pyrrole and pyridine in neat acetonitrile with
Et3N and in buffered aqueous acetonitrile (pH 9) afforded
the adducts 17 and 18, respectively, together with the
debrominated product 16, which became the main product
(Scheme 4). The process is more efficient in neat acetonitrile
and under basic aqueous solution (pH 9) than in aqueous
acetonitrile at pH 7.8 (Table 2).
Fluorescence and Phosphorescence Measurements. The
fluorescence emission spectra of 5 and 10 (both 10-5 M) are
shown in Figure 1. The emission maxima are centered at λmax
) 358 nm for naphthol 10 and 372 nm for 5. The decrease in
fluorescence intensity passing from 10 to the Br-naphthol 5 is
1036 J. Org. Chem. Vol. 74, No. 3, 2009

Photoarylation/Alkylation of Bromo-naphthols
The latter evidence, together with the lack of fluorescence
quenching caused by Et3N (e2 × 10-2 M), suggests that the
amine acts as a triplet rather than a singlet quencher. In addition,
a very similar transient has been recorded also for the methyl
and TBS ethers (6 and 7, respectively).
In contrast, the lifetimes of the triplet states 36* and 37* were
not significantly affected by Et3N addition. These LFP data,
together with the photoreactivity of 5 in neat ACN in the
presence of Et3N and the effect of the oxygen on the photore-
activity in aqueous ACN discussed above, suggest that (i) Et3N
reacts with the triplet excited state and (ii) the reactivity could
be triggered by a deprotonation process of the naphthol in the
3
triplet excited state. The quenching of 5* by Et3N should not
be ascribed to a photoinduced electron transfer (PET) process,
since when the naphthol OH is protected, no significant lifetime
reduction of the triplet excited state (36* and 37*) was recorded.
Electrochemical Measurements. To rule out the mechanism
FIGURE 2. Transient absorption spectra of 5 in acetonitrile. The spectra
were taken 0.1, 1, 2, 4, and 15 µs after the laser pulse, respectively.
Inset a shows the decay traces with O2 (fine line) and without (thicker
line), monitored at 460 nm. Inset b shows the decay traces without
and with Et3N (3 × 10-4, 6 × 10-4, 2 × 10-3, 3 × 10-3 M,
respectively), monitored at 460 nm.
3
of photoinduced electron transfer (PET) from Et3N to 5*, we
had to measure the reduction potential of 5 and 6 by cyclic
voltammetry. Typical voltammograms of 5 in ACN 0.1 M
nBu4PF6 have been measured using glassy carbon disk electrode
versus Ag/AgCl. The reduction waves for the naphthols 5 and
6 were always chemically irreversible using scan rates from 100
to 1300 mV s-1, without the formation of anodic peaks. The
cathodic peak potentials [Epc - Ered(5)] measured using a scan
rate of 100 mV s-1 were similar: -2.29 and -2.40 V for 5 and
6 respectively. Using the literature oxidation potential of Et3N
in ACN [Eox(Et3N), +1.19 V vs NHE; +0.991 V vs Ag/AgCl
in ACN]16 and the energy of 35* [E(35*), evaluated from
phosphorescence measurements], we have been able to estimate
the PET as strongly endoergonic by 15 kcal/mol, using eq 1:
remarkable in both neat ACN (Figure 1a) and in aqueous ACN
(Figure 1b). These results can be interpreted in terms of an
internal heavy-atom effect, which should increase the intersys-
tem crossing (ISC) efficiency. In addition, the fluorescence of
both 5 and 6 is not quenched by Et3N (2 × 10-2 M) in ACN
solution, and it does not change by more than 10% passing from
neat ACN to aqueous ACN. The above evidence together with
the lack of reactivity in air-equilibrated aqueous ACN (without
Et3N) discussed above suggest that the triplet state could be
involved in the reactivity of 5. Therefore, the phosphorescence
spectrum of 6-bromo-2-naphthol was recorded in EPA (diethyl
ether/isopentane) glassy matrices at 77 K to evaluate its energy.
From the onset of the spectrum (Figure 1c) it has been possible
∆Get ) 23.06[Eox(Et3N) - Ered(5)] - E(35*)
(1)
Therefore, the PET mechanism cannot play a significant role
in the quenching of 35* by Et3N, as supported by the evidence
3
that 6* lifetime does not change in ACN in the presence of
3
to evaluate the energy of 5* (E0,T ) 60.5 kcal mol-1).
the amine.
Further Laser Flash Photolysis Studies: Detection of
Transients Arising from 35*. Photolysis of an air-equilibrated
solution of 5 in ACN in the presence of Et3N (5 × 10-2 M),
immediately after the pulse produces a spectrum similar to that
of Figure 2. After decay of the triplet signal, a long-lived
absorption (t1/2 > 20 µs) with a broad absorption band from
540 to 650 nm remains (Figure 3). Such a new transient species
is formed only in the presence of O2. The inset of Figure 3
displays a rising time at 580 nm, which parallels the decay of
35* at 460 nm. These traces suggest a sequential generation of
Laser Flash Photolysis Studies: Generation and Quench-
ing of 5*. The photoactivation processes of 5 have also been
3
studied by laser flash photolysis (LFP), with the aim to clarify
(i) the nature of the excited state involved and (ii) the role of
the Et3N and (iii) to detect further transient species. Indeed,
LFP of 5 at 266 nm (4 mJ/pulse, Nd:YAG laser) in neat ACN
and aqueous ACN (pH 7, buffered conditions) yielded an intense
transient absorbance centered at λmax ) 460 nm, which was
efficiently quenched by O2 (Figure 2, inset a).
Therefore, based also on the spectroscopic similarity of triplet
3
excited state of 10 (310*) (λmax ) 430 nm),15 the above transient
the new species starting from 5*. Grabner’s group has shown
that 3 in its triplet state (33-C), generated from the photolysis
of 1 (Scheme 5), reacts with oxygen yielding benzo-1,4-quinone-
O-oxide (13-CO).3a,b This latter species exhibits a broad
absorption band (420-580 nm) with a maximum centered at
460 nm (Scheme 5).3a,d Therefore, taking also into consideration
that 5exhibits a more extended conjugation in comparison to 1,
we believe that the transient with absorbance from 530 to 650 nm
may be assigned to the carbonyl oxide 15-CO. This intermediate
is generated in the trapping reaction of the triplet carbene 35-C by
molecular oxygen, and further ISC (Scheme 5). This rationalization
agrees with the product analysis in the preparative irradiation in
the presence of O2, with generation of 2,6-dihydroxynaphthalene,
after reductive workup.
3
has been attributed to 5*. The intensity of the end of pulse
signals assigned to the triplets of the Br-naphthols 5-7 is at
3
least 10-fold higher than that of 10*. This result is consistent
with the fluorescence measurements, suggesting that for the Br-
naphthols 5-7, the singlet state is converted into the triplet by
rapid ISC. The profile of such a transient absorbance follows
mainly a second-order decay in the absence of O2 in neat ACN
(Figure 2, inset a, darker line), and in aqueous ACN it is slightly
faster. The decay became a pseudo-first-order upon addition of
Et3N, in the concentration range 3 × 10-4-3 × 10-3 M (Figure
2, inset b), with a k2 ) 9.0((1.0) × 107 M-1 s-1 and without
significant bleaching of the transient signal after the laser shot.
(15) Kleinman, M. H.; Flory, J. H.; Tomalia, D. A.; Turro, N. J. J. Phys.
Chem. B 2000, 104, 11472–11479.
(16) Liu, W.-Z.; Bordwell, F. G. J. Org. Chem. 1996, 61, 4779–4783.
J. Org. Chem. Vol. 74, No. 3, 2009 1037

Pretali et al.
SCHEME 6. Isodesmic Reactions Used To Calculate the
3
pKa of 5* at R(U)B3LYP/6-31+G (d,p) Level of Theory and
UAHF Radii in Aqueous Solution
FIGURE 3. Transient absorption spectra of 5 in ACN with Et3N
(5 × 10-2 M), in the presence of O2 (air-equilibrated solution). The
spectra were taken 80, 100, 120, 150, and 200 ns after the laser
pulse, respectively. The inset shows the decay traces monitored at
460 and 580 nm.
the presence of Et3N has to be ascribed to the carbene
intermediate 5-C.
3
DFT Calculations: Properties and Reactivity of the
Transients. To gather additional evidence in support of a
heterolysis triggered by a deprotonation process of the triplet
SCHEME 5. Parallel Photoreactivity of 1 and 5
3
3
excited state 5*, we have computed (i) the acidity of 5* and
(ii) the potential energy surface (PES) describing the heterolytic
3
fragmentation of the anion 5-, generating the carbene inter-
mediate 35-C and bromide anion in ACN solution. The reactivity
of 33-C with H-donors and molecular oxygen is well-
documented,3 but our product distribution analysis reveals also
a reactivity with aromatics. Therefore we also decided to
3
investigate the reactivity of 5-C with pyrrole and pyridine.
Triplet State Acidity. We have evaluated the thermochem-
3
istry of the deprotonation step of 5*, computing its pKa in
aqueous solution at PCM-UB3LYP/6-31+G(d,p) level of theory,
3
using UAHF radii. Geometries and energies of 5, 5*, and its
3
3
related anion 5- allowed the calculation of 5* pKa using the
isodesmic reaction in Scheme 6 and the ground state pKa of 5
[pKa,exp (5) ) 9.23]18 by eq 2, in order to cancel computational
systematic errors.
pKa(35*) ) pKa,exp(5) + ∆G(35*) ⁄ 2.303RT
(2)
Flash photolysis of 5 in deoxygenated ACN in the presence
of Et3N (4 × 10-2 M) leads to the appearance of another
transient with an absorption spectra blue-shifted in comparison
to that of 11-CO (λmax ) 480 nm, Figure 4). This transient is in
excellent agreement with the reported spectrum of 2-naphthoxyl
radical,17 which should arise from the carbene 35-C, by hydrogen
abstraction. This transient decays with a pseudo-first-order
kinetic, exhibiting a lifetime dependent on Et3N concentration
∆G(35*) is the reaction Gibbs energy for the proton transfer
equilibrium in Scheme 6 (-6.8 kcal mol-1), which has been
computed in aqueous solution at U(R)B3LYP/6-31+G(d,p) level
of theory using PCM solvation model, and UAHF radii.
3
The resulting pKa for 5* (pKa 4.2) suggests that the lowest
triplet excited state is more acid than the singlet ground state
but also less acid than the singlet excited state of phenols.19
Therefore the deprotonation process generating the anion in its
triplet state should be thermodynamically favored in the presence
of a base (Et3N), particularly in neat ACN.
(k2 ) 9.2 × 105 M-1
s
-1). We were unable to directly detect
the carbene 35-C in the presence of Et3N. These LFP data seem
to support the conclusion that the observed reactivity of 5 in
Heterolytic Fragmentation Process. With the aim to evalu-
ate the reactivity of the 6-Br-naphtholate anion in its triplet state
(35-), we computationally explored the potential energy surface
(PES) for its heterolytic fragmentation, generating the interme-
3
diate 5-C and bromide anion in ACN solution (Scheme 7).
The anion in the lowest triplet state 35-, the TS TS-35-, and the
3
intermediate 5-C have been optimized at PCM-R(U)B3LYP/6-
31+G(d,p) level of theory in ACN solution, using both UA0 and
UHF radii. The TS-35- is very “early” (Figure 5), exhibiting an
(17) (a) Das, T. N.; Neta, P. J. Phys. Chem. A 1998, 102, 7081–7085. (b)
Das, P. K.; Encinas, M. V.; Steenken, S.; Scaiano, J. C. J. Am. Chem. Soc.
1981, 103, 4162–4166.
(18) (a) Rosenberg, J. L.; Brinn, I. M. J. Chem. Soc., Faraday Trans. 1 1976,
72, 448–452. (b) Rosenberg, J. L.; Brinn, I. M. J. Phys. Chem. 1972, 76, 3558–
3562.
(19) (a) Gao, J.; Li, N.; Freindorf, M. J. Am. Chem. Soc. 1996, 118, 4912–
4913. (b) Granucci, G.; Hynes, J. T.; Millie, P.; Tran-Thi, T.-H. J. Am. Chem.
Soc. 2000, 122, 12243–12253. (c) Jacoby, C.; Boehm, M.; Vu, C.; Ratzer, C.;
Schmitt, M. Chem. Phys. Chem. 2006, 7, 448–454.
FIGURE 4. Transient absorption spectra of 5 in ACN with Et3N
(4 × 10-2 M), in the absence of O2 (Ar-equilibrated solution). The
spectra were recorded 0.2, 0.3, 0.5, 1, and 2 µs after the laser
pulse.
1038 J. Org. Chem. Vol. 74, No. 3, 2009

Photoarylation/Alkylation of Bromo-naphthols
3
3
SCHEME 7. Generation of the Carbene 35-C Investigated at
R(U)B3LYP/6-31+G(d,p) Level of Theory in ACN Solution
SCHEME 8. Comparison of the SOMOs for 3-C and 5-C
Using Schematic Representations, Which Reveals the
3
Pronounced Aryl Radical Nature of 5-C at C6
TABLE 3. Gibbs Free Energy (G, in hartree), Thermal Correction
to Gibbs Free Energy (δG, in hartree), and Activation Gibbs Free
Energy (∆Gq, in kcal mol-1) for the Heterolysis of the C-Br Bond in
the 6-Br-Naphtholate Anion Triplet State (35-), in ACN at
SCHEME 9. Arylation/Alkylation Reaction Mechanism
Involving 5-C
3
PCM-R(U)B3LYP/6-31+G(d,p) Level with Both UA0 and UAHF Radii
stationary points
GCH CN
δG
∆Gq
3
35-
-3031.717083a
-3031.717072b
-3031.708401a
-3031.705893b
0.087107a
4.36a
5.93b
TS-35-
0.085366a
a PCM-UB3LYP/6-31+G(d,p), UA0 radii. b PCM-UB3LYP/6-31+G(d,p),
UAHF radii.
almost planar structure with the C-Br bond undergoing heterolytic
cleavage stretched from 1.984 Å in 35- to 2.131 Å in TS-35- [in
ACN, at PCM-R(U)B3LYP/6-31+G(d,p) level of theory].
The activation free energy for the heterolytic fragmentation
in ACN is very low, being only 4.4 kcal mol-1. Similar results
of both the intermediate 33-C and 35-C should resemble that of
an aryl radical, in contrast to an aliphatic carbene, which exhibits
two equivalent singly occupied p-like orbitals. In addition, the
total spin density for 35-C is mainly localized on the C6 (in the
naphthalene plane) and on both the oxygen and C1 atoms
(orthogonal to the naphthalene plane, see Scheme 8 and Figure
6). In contrast, the total spin density for 33-C is mainly localized
only on the C4 and on the oxygen atom.
q
have also been obtained using UAHF radii (∆G ) 5.9 kcal
mol-1; Table 3). The reaction path from TS-35- downhill to
3
the intermediate 5-C followed by IRC calculations at PCM-
B3LYP/6-31+G(d,p) level, in ACN, demonstrated the direct
3
connection between the TS-35- to the final intermediate 5-C
and bromide anion, which form a complex (at 3.018 Å C6-Br
distance) lying 8.8 kcal mol-1 below the reactants. These data
unequivocally suggest that the heterolysis of the C-Br bond,
triggered by the deprotonation of the triplet excited state, is
kinetically the most accessible reaction pathway for the triplet
In other words, the naphthalene delocalization causes a
lessening of the carbene-like character on the C6 carbon. This
3
3
evidence suggests that passing from 3-C to 5-C there is a
further shift from a carbene-like to an aryl radical-like character.
Therefore, the aryl radical nature at the C-atom should be more
3
3
excited state 5*. The triplet state of the intermediate 5-C,
resulting from the heterolysis of 35-, displays a planar geometry,
while the singlet (15-C) exhibits the C6 slightly bent out of plane
3
3
pronounced for 5-C than for 3-C.
3
Reactivity of 5-C with Pyrrole and Pyridine. We also
3
1
and puckered (Figure 5). 5-C is much more stable than 5-C
by 18.8 and 20.6 kcal mol-1, in ACN solution and in gas phase,
respectively.
explored the generation of the final adducts starting from the
intermediate 35-C, investigating the triplet PES for the carbene
addition to pyrrole and pyridine. The calculations have been
performed in ACN solution (by PCM solvation models), in the
frame of DFT, using B3LYP, PBE0, and MPWB1K functionals.
We had chosen these three functionals because B3LYP is the
most widely employed in organic reactivity,11 PBE0 has been
extensively used by Barone for predicting reactivity in polar
media,12 and the MPWB1K functional has been explicitly
recommended by Thrular for thermochemical kinetics.13 We
have been able to localize both TSs (TS-Py and TS-Pyrr) and
3
3
Comparison between Carbenes 3-C and 5-C. Grabner,
analyzing the orbitals of 33-C (at AM1 level of theory),
suggested that the pz orbital of C4 can be considered a frontier
orbital, strongly localized and singly occupied (Scheme 8).
The other nearly degenerative orbital can be constructed from
the C4 px orbital in conjugation with the π orbitals of the enone
system.3a The intermediate 35-C exhibits [at UB3LYP/6-
31+G(d,p) level] a very similar singly occupied pz-like orbital
on C6 and another one almost degenerate, which can be
constructed from the C6 px orbital in conjugation with the
extended π orbitals of the naphthalene aromatic system (Scheme
8). Therefore, as already suggested by Grabner,3a the reactivity
3
intermediates (3I-Py and I-Pyrr) along the radical arylation
pathways (Scheme 9).
Geometries and energies (Table 4) of the stationary points
in Figure 7 are very similar using the different functionals. TS
3
geometries (TS-Pyrr and TS-Py) suggest that 5-C reacts as
an aryl radical with only one C-C forming bond.
FIGURE 5. Geometries of the stationary points TS-35-, 35-C, and 15-
C, in acetonitrile solution at PCM-UB3LYP/6-31+G(d,p) level of
theory, using both UA0 and UAHF radii (in parenthesis).
3
3
FIGURE 6. Spin density isosurfaces of 3-C and 5-C, at UB3LYP/
6-31+G(d,p) level of theory, in the gas phase.
J. Org. Chem. Vol. 74, No. 3, 2009 1039

Pretali et al.
TABLE 4. Gibbs Free Energy (G, in hartree) and Activation
Gibbs Free Energy (∆Gq, in kcal mol-1) for the Radical Arylation of
acetonitrile in the presence of Et3N, using product distribution
analysis, LFP, CV measurements, and DFT calculations in
condensed phase. We have shown that, similarly to 4-chlo-
rophenol, 6-Br-naphthol photogenerates the triplet carbenes 35-C
3
Pyrrole and Pyridine by 5-C, in ACN using B3LYP, PBE0, and
MPWB1K Functionals with 6-31+G(d,p) Basis Set and PCM
Solvation Model
3
starting from the triplet exited state 5. The carbene can be
stationary points
GCH CN
∆Gq
3
trapped efficiently by oxygen to give the detectable 2,6-
naphthoquinone-O-oxide (530 < λ < 650 nm). 35 is less basic
than the excited state of 1, and unlike the 4-chlorophenols,
photoheterolysis requires the deprotonation by an added amine
(Et3N). PET has been ruled out from the possible reaction
mechanisms. The product distribution analysis of the photore-
actions in the presence of several alkenes and aromatics, together
with a DFT computational investigation, suggests that the aryl
radical nature of the carbene 35-C is more pronounced than that
of Grabner’s carbene 3. Such a difference allows the achieve-
ment of a fairly efficient arylation/alkylation of aromatics and
alkenes, through a radical-like pathway.
35-C
-459.822409 a
-459.284591 b
-459.590222 c
-708.118249 a
-707.281959 b
-707.751524 c
-670.013339 a
-669.222087 b
-669.666239 c
TS-Py
6.3a
5.3b
6.1c
2.2a
1.7b
2.0c
TS-Pyrr
a PCM-R(U)B3LYP/6-31+G(d,p) UA0 radii; pyrrole: -210.194536;
pyridine: -248.305986. b PCM-R(U)PBE0/6-31+G(d,p), UAHF radii; pyrrole:
-209.940134; pyridine: -248.005876. c PCM-R(U)MPWB1K/6-31+G(d,p),
UAHF radii; pyrrole: -210.079160; pyridine: -248.171050.
Experimental Section
Bromo-naphthol 5 and 2,6-dihydroxynaphthalene were used without
further purification. The other substituted naphthols (6-8) were
synthesized via standard procedures already published.20 Compounds
10 and 16 have been identified by comparison to other authentic
samples.
Procedure for Irradiation of 5 in the Presence of Pyrrole.
An argon-purged solution of 5 (134 mg, 0.6 mmol), freshly distilled
pyrrole (2.01 g, 30 mmol), and Et3N (120 mg, 1.0 mmol) in 300 mL
of CH3CN was irradiated in Pyrex tubes (20 mL) for 1 h, by a
multilamp reactor fitted with four 15 W lamps, with maximum
emission centered at 360 nm. Chromatographic separation (cyclohex-
ane/ethyl acetate ) 7: 3), following solvent removal by vacuum
concentration, gave 41 mg of 11 (83% yield) and 4 mg of 10 (4%
yield).
FIGURE 7. TSs (TS-Pyrr and TS-Py) and intermediates (3I-Pyrr and
3
3I-Py) for the radical arylation of pyrrole and pyridine, by 5-C using
B3LYP, PBE0 (bold characters), and MPWB1K (in parenthesis)
functionals and 6-31+G(d,p) basis set, in acetonitrile as solvent
(modeled by PCM solvation model and UA0 radii).
1
6-(1H-Pyrrol-2-yl)-naphthalen-2-ol (11). Green oil. H NMR
(200 MHz, acetone-d6): δ 6.10-6.25 (m, 1H), 6.55-6.65 (m, 1H),
6.80-6.95 (m, 1H), 7.00-7.25 (m, 2H), 7.55-7.80 (m, 3H), 8.00 (s,
1H), 8.60 (s, 1H), 10.50 (broad s, 1H). 13C NMR (acetone-d6): δ 106.7,
110.2, 110.5, 119.9, 120.1, 122.0, 124.9, 127.8, 129.4, 130.1, 130.3,
130.4, 134.7, 156.2. Anal. Calcd for C14H11NO: C, 80.36; H, 5.30; N,
6.69; O, 7.65. Found: C, 80.30; H, 5.35; N, 6.69.
General Procedure for Irradiation of 5 in the Presence of
Alkenes and Pyridine. Experiments were carried out as described
above using a solution of 5 (2 × 10-3 M) and Et3N (2 × 10-3 M)
after adding the traps: allyltrimethylsilane, 2,3-dimethyl-2-butene,
acrylonitrile, pyridine, morpholine, and EVE (1-5 × 10-2 M), in
acetonitrile.
The radical arylation of pyrrole by 35-C, generating the
intermediate 3I-Pyrr (Scheme 9) is an almost barrierless process,
since the early TS-Pyrr lies 2.2 kcal mol-1 (Table 4) above
the reactants, in ACN solution. The radical arylation of pyridine
at C3 is slightly more endoergonic, but the activation Gibbs
energy in ACN is still very low (e6.3 kcal mol-1). Therefore,
the radical arylation should compete efficiently with the
3
polymerization of 5-C.
It is interesting to stress at this point that the triplet PES lies
below the singlet PES from the reactants (35-C + heteroaro-
matic) to TSs included, for the arylation of both pyrrole and
pyridine. In contrast, the intermediate I-Pyrr is less stable in
the triplet state (3I-Pyrr) than in the singlet state (1I-Pyrr) by
at least 5.8 kcal/mol [from a single point calculation on the
optimized geometry of the triplet state, at PCM-UB3LYP/6-
31G(d,p) level], unlike I-Py, which is still more stable in the
lowest triplet state (3I-Py, by 17.7 kcal/mol). Therefore, downhill
from the TS-pyrr there could be a triplet-singlet PES crossing
point, leading to a zwitterionic intermediate in its singlet state
and to the final observed product by proton transfer. Such a
mechanism should be operative also for the arylation of
allyltrimethylsilane, since from product distribution analysis the
TMS cation loss was the only process detected.
6-Allylnaphthalen-2-ol (9). White crystals. Mp 90.1-90.3 °C.
1H NMR (300 MHz, CDCl3): δ 3.55 (d, 3JH,H ) 6.4 Hz, 2 H), 5.13
(broad s, 1H) 5.19-5.23 (m, 2 H), 6.03-6.20 (m, 1 H), 7.00-7.20
3
(m, 2 H), 7.30-7.40 (m, 1 H), 7.59 (s, 1H) 7.64 (d, JH,H ) 8.4
Hz, 1H), 7.72 (d, 3JH,H ) 8.7 Hz, 1H). 13C NMR (CDCl3): δ 40.1,
109.3, 115.8, 117.7, 126.4, 126.5, 128.0, 129.0, 129.3, 133.1, 135.1,
137.4, 152.8. Anal. Calcd for C13H12O: C, 84.75; H, 6.57; O, 8.68.
Found: C, 84.66; H, 6.67.
6-(1,1,2-Trimethylallyl)naphthalen-2-ol (12). Colorless oil. 1H
NMR (200 MHz, acetone-d6): δ 1.50 (s, 9 H), 4.90 (t, 3JH,H ) 2.0 Hz,
1 H), 5.05 (broad s, 1 H), 7.05-7.20 (m, 2 H), 7.30 (dd, 3JH,H ) 10.0
3
3
Hz, JH,H ) 2.0 Hz, 1 H), 7.60 (d, JH,H ) 10.0 Hz, 1 H), 7.70 (d,
3JH,H ) 2.0 Hz, 1 H), 7.75 (d, JH,H ) 10.0 Hz, 1 H), 8.60 (s, 1 H).
3
13C NMR (CDCl3): δ 20.8, 29.0, 44.9, 109.9, 110.5, 119.5, 124.9,
(20) (a) Groves, J. T.; Viskif, P. J. Org. Chem. 1990, 55, 3628–3634. (b)
Mewshaw, R. E., Jr.; Yang, C.; Manas, E. S.; Xu, Z. B.; Henderson, R. A., Jr.;
Harris, H. A. J. Med. Chem. 2005, 48, 3953–3979. (c) Murphy, R. A.; Kung,
H. F.; Kung, M. P.; Billings, J. J. Med. Chem. 1990, 33, 171–178. (d) Li, X.;
Hewgley, J. B.; Mulrooney, C. A.; Yang, J.; Kozlowski, M. C. J. Org. Chem.
2003, 68, 5500–5511.
Conclusions
In this paper we have described the photoreactivity of the
triplet excited states of 6-bromonaphthols in water and in
1040 J. Org. Chem. Vol. 74, No. 3, 2009

Photoarylation/Alkylation of Bromo-naphthols
126.9, 127.3, 129.8, 130.7, 134.8, 143.9, 153.9, 156.4. Anal. Calcd
for C16H18O: C, 84.91; H, 8.02; O, 7.07. Found: 84.88; H, 8.09.
3-Bromo-3-(6-hydroxynaphthalen-2-yl)propionitrile (13). Col-
orless oil. 1H NMR (300 MHz, acetone-d6): δ 3.50 (d, 3JH,H ) 8.0
MHz, DMSO): δ 4.30 (s, 1 H), 7.40 (s, 1 H), 7.65-7.85 (m, 1 H),
7.80-8.00 (m, 2 H), 8.30-8.50 (m, 2 H), 8.70 (m, 2 H), 9.15 (s,
1 H). 13C NMR: δ 109.6, 119.6, 122.7, 124.1, 125.5, 127.1, 128.6,
131.2, 131.7, 133.9, 135.1, 136.4, 145.8, 146.2, 158.8, 175.7. Anal.
Calcd for C16H10NNaO3: C, 66.90; H, 3.51; N, 4.88; Na, 8.00; O,
16.71. Found: C, 66.79; H, 3.59; N, 4.83.
3
Hz, 2 H), 4.50 (t, JH,H ) 7.7 Hz, 1 H), 5.10 (s broad, 1 H),
7.00-7.15 (m, 2 H), 7.25-7.40 (m, 1 H), 7.60-7.90 (m, 3 H). 13
C
NMR (acetone-d6): δ 27.2, 42.7, 109.3, 116.9, 118.4, 127.2, 127.2,
128.4, 128.7, 128.8, 129.7, 134.1, 153.8. Anal. Calcd for
C13H10BrNO: C, 56.55; H, 3.65; Br, 28.94; N, 5.07; O, 5.79. Found:
C, 56.63; H, 3.69; Br, 28.79; N, 5.11.
Electrochemical Measurements. Cyclic voltammetries (CV)
were performed using a BAS EPSILON for Electrochemistry
equipped with a glassy carbon disk electrode and a Ag/AgCl/KCl
(4 M KCl saturated with AgCl) reference electrode, in degassed
acetonitrile using Bu4NPF6 0.1 M, sweep rate from 100 to 1500
mV s-1. All potentials in the text are reported vs Ag/AgCl/KCl (4
M KCl saturated with AgCl).
6-Pyridin-3-yl-naphthalen-2-ol (14). White crystals. Mp 250-252
1
°C. H NMR (300 MHz, DMSO-d6): δ 7.10 (m, 2 H), 7.60 (dd,
3JH,H ) 7.9 Hz, 3JH,H ) 4.8 Hz, 1 H), 7.80-7.90 (m, 3 H), 8.20 (s,
1 H), 8.30 (d, 3JH,H ) 7.9 Hz, 1 H), 8.60 (d, 3JH,H ) 4.8 Hz, 1 H),
9.00 (s, 1 H), 9.90 (broad s, 1 H). 13C NMR (DMSO-d6): δ 108.1,
118.9, 124.1, 124.5, 125.5, 126.6, 127.4, 129.6, 130.0, 133.9, 135.1,
135.9, 145.8, 146.2, 155.6. Anal. Calcd for C15H11NO: C, 81.43;
H, 5.01; N, 6.33; O, 7.23. Found: 81.33; H, 5.10; N, 6.01.
General Procedure for Irradiation of 5 in the Presence of
1,4-Dimethoxybenzene. An argon-purged solution of 5 (134 mg,
0.6 mmol), 1,4-dimethoxybenzene (0.828 g, 20 mmol), and Et3N
(120 mg, 1.0 mmol) in 300 mL of CH3CN was irradiated in Pyrex
tubes (20 mL) for 1 h by a multilamp reactor fitted with four 15 W
lamps, with maximum emission centered at 360 nm. Chromato-
graphic separation (cyclohexane/ethyl acetate ) 9:1), following
solvent removal by vacuum concentration, gave 34 mg of 10 (20%
yield) and 60 mg of 15 (70% yield).
Methods and Computation Details. All calculations were
carried out using Revision D.02 of the Gaussian 03 program
package.21 The structures of the triplet excited state of 35* and the
intermediates (35-, 35-C, 15-C, 3I-Py, and 3I-Pyrr) and the transition
states (TS-35-, TS-Py, and TS-Pyrr) were fully optimized in the
gas phase and in acetonitrile solution using the B3LYP,11 PBE0,12
and MPWB1K13 functionals, with the 6-31+G(d,p) basis set. It is
known that diffuse functions are mandatory for a reliable evaluation
of anion energies and H-bonding, and in our reactive system an
anionic character is present in both the triplet state 35- and also at
the oxygen atom in 35-C. Thermal contributions (∆G) to activation
free energy were computed from B3LYP/6-31+G(d,p) structures
and harmonic frequencies, by using the harmonic oscillator ap-
proximation and the standard expressions for an ideal gas in the
canonical ensemble at 298.15 K and 1 atm. The optimization of
the stationary points in the solvent bulk were calculated via the
self-consistent reaction field (SCRF) method using PCM as
implemented in the D.02 version of Gaussian 03.21 Such a model
includes the nonelectrostatic terms (cavitation, dispersion, and
repulsion energy) in addition to the classical electrostatic contribu-
tion. The cavities within the solvent are composed by interlocking
spheres centered on non-hydrogen atoms with both UA0 and UAHF
radii.
6-(2,5-Dimethoxy-phenyl)-naphthalen-2-ol (15). Colorless oil.
1H NMR (300 MHz, CDCl3): δ 3.79 (s, 3 H), 3.85 (s, 3 H), 5.04
3
3
(bs, 1 H, -OH), 6.90 (dd, JH,H ) 8.9 Hz, JH,H ) 3.0 Hz, 1 H),
3
3
6.98 (d, JH,H ) 8.9 Hz, 1 H), 7.02 (d, JH,H ) 3.0 Hz, 1 H), 7.12
(dd, 3JH,H ) 8.8 Hz, 3JH,H ) 2.5 Hz, 1 H), 7.18 (d, 3JH,H ) 2.5 Hz,
1 H), 7.66 (dd, 3JH,H ) 8.5 Hz, 3JH,H ) 1.7 Hz, 1 H), 7.72 (d, 3JH,H
) 8.5 Hz, 1 H), 7.80 (d, JH,H ) 8.8 Hz, 1 H), 7.92 (bs, 1 H). 13C
3
NMR (300 MHz, CDCl3): δ 55.74, 56.32, 109.19, 112.72, 112.95,
116.78, 117.70, 125.67, 127.86, 128.47, 128.77, 130.01, 131.63,
133.54, 133.72, 150.88, 153.36, 153.74. Anal. Calcd for C18H16O3:
C, 77.12; H, 5.75; O, 17.12. Found: C, 77.20; H, 5.63.
Procedure for Irradiation of 8 in the Presence of Pyrrole
in Acetonitrile. A N2-purged solution of 8 (160 mg, 0.6 mmol),
freshly distilled pyrrole (2.01 g, 30 mmol) and Et3N (122 mg, 1.1
mmol) in 300 mL of CH3CN was irradiated in Pyrex tubes (20
mL) for 1 h, by a multilamp reactor fitted with four 15 W lamps,
with maximum emission centered at 360 nm. Reverse phase
chromatographic separation on RP-C18 silica (MeOH/H2O ) 6:
4), following solvent removal by vacuum concentration, gave 59
mg of 16 (52% yield) and 43 mg of 17 (20% yield).
Acknowledgment. Financial support from Pavia University
(“Fondo FAR 2007”) and “Consorzio CINMPIS” is gratefully
acknowledged. We also thank CICAIA (Modena University)
and CINECA (Bologna University) for computer facilities.
Supporting Information Available: 1H NMR, and 13C NMR
spectra for the adducts 9, 11-15, 17, and 18, electrochemical
data (Figures S1 and S1a), Cartesian coordinates of reactants
and intermediates (35-, 35-C, 15-C, 3I-Py and 3I-Pyrr) and the
transitionstates(TS-35-,TS-Py,andTS-Pyrr)attheR(U)B3LYP/
6-31+G(d,p) R(U)PBE0/6-31+G(d,p) and MPWB1K/6-
31+G(d,p) level (gas phase and acetonitrile solution). This
material is available free of charge via the Internet at
http://pubs.acs.org.
3-Hydroxy-7-(1H-pyrrol-2-yl)naphthalene-2-carboxylic Acid Tri-
ethylammonium Salt (17). Pale green crystals. Mp 95-97.2 °C.
3
1H NMR (300 MHz, CD3OD): δ 1.20 (t, JH,H ) 7.3 Hz, 9 H),
3
3.10 (q, JH,H ) 7.3 Hz, 6 H), 4.90 (s, 1 H), 6.15 (m, 1 H), 6.50
3
(m, 1 H), 6.85 (m, 1 H), 7.10 (s, 1 H), 7.55 (d, JH,H ) 8.7 Hz, 1
3
3
H), 7.70 (dd, JH,H ) 8.7 Hz, JH,H ) 1.7 Hz, 1 H), 7.90 (s, 1 H),
8.40 (s, 1 H). 13C NMR (CD3OD): δ 9.4, 48.0, 106.6, 110.4, 111.1,
120.2, 122.7, 122.8, 126.5, 127.5, 129.3, 129.9, 132.8, 133.4, 137.0,
158.8, 175.7. Anal. Calcd for C21H26N2O3: C, 71.16; H, 7.39; N,
7.90; O, 13.54. Found: C, 70.87; H, 7.49, N, 7.79.
JO802374R
(21) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci,
B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.;
Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian,
H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski,
J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg,
J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.;
Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.;
Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.
Al-Laham, M. A. Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill,
P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.
Gaussian 03, ReVision D.02; Gaussian, Inc.: Wallingford, CT, 2004.
Procedure for Irradiation of 8 in the Presence of Pyridine
in Aqueous Acetonitrile. A N2-purged solution of 8 (161 mg, 0.6
mmol), freshly distilled pyridine (5.0 g. 4.8 mL, 63 mmol), and Na2CO3
(1.30 g, 12.3 mmol) in 300 mL of CH3CN/H2O ) 1:1 was irradiated
in Pyrex tubes (20 mL) for 1 h by a multilamp reactor fitted with four
15 W lamps, with maximum emission centered at 360 nm. Reverse
phase chromatographic separation on RP-C18 silica (MeOH/H2O )
6:4), following solvent removal by vacuum concentration, gave 64
mg of 16 (57% yield) and 36 mg of 18 (21% yield).
3-Hydroxy-7-pyridin-3-yl-naphthalene-2-carboxylic
Sodium Salt (18). Yellow solid. Mp > 250 °C. H NMR (200
Acid
1
J. Org. Chem. Vol. 74, No. 3, 2009 1041