Regioselective photochemical C-OMe bond formation initiated by one-electron transfer and N-OMe bond fragmentation in electron donor-acceptor systems

Article abstract of DOI:10.1002/ejoc.201101595

Compounds that integrate electron donor-acceptor subunits with N-methoxyisoquinolinium as acceptors and substituted (methoxy)benzenes as donors were synthesized and their luminescent and photochemical properties studied. Photolysis yielded the corresponding photomethoxylation products in a two-step process that involves N-OMe bond scission followed by C-OMe bond formation. Homolysis of the N-OMe bond restores the aromatic isoquinoline nucleus and produces a methoxy radical that can couple to the required ring carbon atom in the benzene cation radical to give the products in a regioselective process controlled by the spin density of the cation radical. This photoprocess involves two different pathways: methoxylation of the acceptor (intracomponent methoxylation) or the donor (intercomponent metoxylation). Both methoxy-transfer pathways are controlled by the donoating ability (redox potential) of the donor subunit, consistent with the emission observed upon excitation of the charge-transfer state in systems that undergo intermethoxylation.

Full text of DOI:10.1002/ejoc.201101595

FULL PAPER
DOI: 10.1002/ejoc.201101595
Regioselective Photochemical C–OMe Bond Formation Initiated by
One-Electron Transfer and N–OMe Bond Fragmentation in Electron
Donor–Acceptor Systems
Daniel Collado[a] and Ezequiel Perez-Inestrosa*[a]
Dedicated to the memory of Rafael Suau[‡]
Keywords: Photolysis / Electron transfer / Methoxy radical / Aromatic methoxylation / Radical ions
Compounds that integrate electron donor–acceptor subunits
with N-methoxyisoquinolinium as acceptors and substituted
(methoxy)benzenes as donors were synthesized and their lu-
minescent and photochemical properties studied. Photolysis
yielded the corresponding photomethoxylation products in a
two-step process that involves N–OMe bond scission fol-
lowed by C–OMe bond formation. Homolysis of the N–OMe
bond restores the aromatic isoquinoline nucleus and pro-
duces a methoxy radical that can couple to the required ring
carbon atom in the benzene cation radical to give the prod-
ucts in a regioselective process controlled by the spin density
of the cation radical. This photoprocess involves two different
pathways: methoxylation of the acceptor (intracomponent
methoxylation) or the donor (intercomponent metoxylation).
Both methoxy-transfer pathways are controlled by the
donoating ability (redox potential) of the donor subunit, con-
sistent with the emission observed upon excitation of the
charge-transfer state in systems that undergo intermeth-
oxylation.
Our group has conducted research into the development
of reactions induced by photochemical ET, particularly the
photohydroxylation of aromatic donors (Scheme 2) upon
ET to the protonated isoquinoline N-oxide acceptor, by
which an electron is transferred from D to A, while the
hydroxyl group migrates in the opposite direction.[3,4] For-
mally, the overall process involves three main steps, namely:
(1) ET from the donor to the first exited singlet state (S1)
of the acceptor to give a charge transfer (CT) state, (2) N+–
OH bond fragmentation to give a hydroxyl radical and the
donor cation radical, and (3) coupling of the donor cation
radical and hydroxyl radical to give the photohydroxylated
product. Coupling of the ET and bond-breaking steps may
involve a concerted pathway and a stepwise pathway in
Introduction
Electron transfer (ET) reactions initiated by photoexcit-
ation of either a potential electron acceptor (A) or a poten-
tial electron donor (D) from an AD pair has been one of
the most actively investigated areas in the search for new
photochemical reactions. These radical ion pairs are inter-
esting, because many can undergo bond-formation or
bond-fragmentation reactions that are difficult to ac-
complish conventionally (Scheme 1).[1]
Fragmentation reactions of radical ions have found use
in the initiation of radical polymerizations and the design
of new synthetic transformations. In addition, they have
been used as mechanistic probes to detect ET in chemical
and biochemical processes.[2]
Scheme 1.
competition. Establishing whether ET and bond cleavage
occur in a stepwise or concerted manner is crucial to pro-
vide a detailed description of the process, and efforts to
elucidate the competition between the two pathways have
been made.[5] Interest has focussed on the ultrafast N–O
bond-fragmentation reaction by one-electron reduction of
[‡] Deceased November 11, 2010
[a] Department of Organic Chemistry, University of Málaga,
29071 Málaga, Spain
Fax: +34-952133433
E-mail: inestrosa@uma.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101595.
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C–OMe Bond Formation and N–OMe Bond Fragmentation
the corresponding N-methoxypyridinium and -isoquinolin-
ium salts as potentially barrierless ET-initiated chemical re-
actions and on the role of the conical intersection.[6]
Results and Discussion
Compounds 1–5 were prepared by the direct O-methyl-
ation of the corresponding benzylisoquinoline N-oxides[3,4a]
by reaction with dimethyl sulfate followed by exchange of
the counterion with perchlorate (a detailed description is
given in the Supporting Information).
Photophysical Properties
Absorption Spectroscopy
The acceptor–spacer–donor (AsD) systems that com-
prise 1–4 are formed from two chromophores (A is an N-
methoxyisoquinolinium ring, and D is a substituted benz-
ene) covalently connected by a methylene bridge, and their
electronic absorption spectra are very similar. In CH2Cl2,
1–4 exhibit absorption maxima at wavelengths up to
340 nm; however, the maximum for 4 is blueshifted to
324 nm (Figure 1). Essentially, each electronic absorption
spectrum is a combination of the individual spectra for the
two bridged units. For example, Figure 2 shows the spec-
trum of 2; the absorption spectrum for a 1:1 mixture of
subunits A and D (5 and p-methylanisole, respectively) re-
sembles the combination of the isolated subunits (Fig-
ure S1, Supporting Information). The absorption spectrum
is mainly the result of the contribution of the acceptor moi-
ety (N-methoxyisoquinolinium), which is the sole contrib-
utor above 300 nm.
Scheme 2.
This paper describes the synthesis and the photophysical
and photochemical profiles of the bridged N-methoxyiso-
quinoline derivatives 1–4 (Scheme 3), in which the oxygen
atom in the isoquinoline N-oxide is covalently bonded to
the methyl group. As in previous studies on the photophys-
ics and photochemistry of related N-oxides in an acid me-
dium, this precludes a protonation–deprotonation equilib-
rium. We used 5 as a model to compare the photophysical
and photochemical profiles of 1–4. All compounds are solu-
ble in water and dichloromethane.
The isolated and bridged subunits exhibit some special
features in addition to the similarities between their absorp-
tion spectra. For example, 2, in common with the others,
exhibits a small redshift of the absorption maximum for
the bridged subunit relative to the 1:1 mixture and a weak
absorption tail in the 350–400 nm region (Figure 2). As seen
Scheme 3.
Figure 1. Absorption spectra of 1–4 in CH2Cl2.
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Figure 2. Absorption spectra for 2 and a 1:1 mixture of 5/p-methylanisole (2ϫ10–4 m in CH2Cl2).
in Figure 1, this tailed absorption band, which is partially cence emission spectra in CH2Cl2 for 1–4, which contain
overlapped with the common longest-wavelength absorp- the bridged benzene ring as an electron donor with zero (1),
tion maximum of N-methoxyisoquinolinium, is quite strong one (2) or two (3 and 4) methoxy groups as substituents,
in 3, which possesses a better donor group, but ill-defined differ markedly depending on the electron-donating ability
for 1, which has the worst donor group.
and excitation wavelength (Table 1). Thus, 1–3, which have
Compound 4, which contains N-methoxy-6,7-dimeth- an identical electron-acceptor moiety (viz. the N-methoxy-
oxyisoquinolinium, also exhibits a blueshift. A comparison isoquinolinium chromophore), exhibit the same LE-state
of the absorption spectra for equimolar solutions of the iso- emission on excitation at a short wavelength (λexc
=
lated chromophores and 1–4 reveals a small redshift (4 nm) 330 nm). This is clearly the emission band for the N-meth-
consistent with a mild electronic interaction in the ground oxyisoquinolinium chromophore. In 4, which contains the
state. Compounds 1–4 possess a formal positive charge in N-methoxy-6,7-dimethoxyisoquinolinium
chromophore,
the isoquinoline chromophore; as a result, the reduction the LE-state emission is redshifted with respect to that of
potential of N+–OMe is lower than that of the free N-ox- 5, which is indicative of additional dimethoxy substitution
ide.[4a] The absorption spectra of 2–4 in CH2Cl2 exhibit two of the heterocycle. Compound 5 exhibits the same emission
absorption bands at 338 nm and 360–400 nm, which can be profile at any excitation wavelength. At short excitation
assigned to N-methoxyisoquinolinium and CT-band ab- wavelengths, however, only 1, which has an unsubstituted
sorption, respectively.[4] The band is well defined for 2–4 benzene ring as the electron-donor moiety, resembles 5 in
(Figure 1); however, there is an overlap between CT absorp- its emission profile. The other AsD systems (2–4) invariably
tion and strong end absorption of the N-methoxyisoquinol- exhibit a new, redshifted emission band. In 2, which has an
inium chromophore except in 1, the spectrum for which is electron donor with one methoxy group, the new band ap-
similar to the combined spectra of the two chromophore pears at 488 nm; in 3, with two methoxy groups, it appears
units and contains a very weak CT-absorption band. How- at the longest wavelength. This result reflects the CT char-
ever, there always exists substantial overlap between the rel- acter of these fluorescent emission bands. Compound 4 ex-
atively weak CT-absorption band and the strong end ab- hibits a blueshifted emission band consistent with the pres-
sorption of the N-methoxyisoquinolinium chromophore.
ence of two methoxy groups on the acceptor moiety, which
implies a decrease of its electron-acceptor ability. This is
especially significant on excitation at longer wavelengths
(λexc Ͼ 360 nm), where only the CT-emission band is ob-
served. Selective excitation of absorption bands led to dif-
Steady-State Fluorescence Spectroscopy
The fluorescence emission spectra for the compounds ex-
hibit the general trends for oxygen-coordinated isoquinoline
N-oxide derivatives.[7] Covalent bonding of the oxygen atom
to the methyl group causes the fluorescence emission from
the locally excited (LE) state of N-methoxyisoquinolinium
(A) to appear at 378 nm (Figure 3). However, the fluores-
ferent emission spectra that contain two bands at λexc
=
330 nm and a single maximum at λexc = 360 nm. The last
band can be assigned to an intramolecular CT transition.
In 1, this band is very weak, and the maximum of the
fluorescence emission is located at a shorter wavelength,
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C–OMe Bond Formation and N–OMe Bond Fragmentation
Figure 3. Emission spectra at λexc = 330 nm for 1–5 in CH2Cl2.
which indicates that the CT band is scarcely stabilized. The Table 1. Absorption (λmax), emission (λfl) and fluorescence quan-
tum yield (Φ) of 1–5 in CH2Cl2.
increased electron-donating ability of 3 relative to 2 results
Compound
λmax (ε, 102)
λfl (Φ, 10–3)
in a redshift of its CT emission band. Conversely, the de-
creased electron-accepting ability of 4 relative to 3 reverses
the effect.
Compounds 2–4 exhibit a double emission band at λexc
= 330 nm, which corresponds to the LE chromophore and
CT emission. The quantum-yield ratio between these two
emissions (1.25 for 2 and 1.5 for 3) facilitates ET in all cases
(Figure 4). The ratio increases to 13.3 for 4, which exhibits
highly efficient ET judging by reported data for its N-oxide
analogue.[3]
λexc = 330 nm
λexc Ͼ 360 nm
1
2
3
4
5
342 (113)
338 (59)
338 (58)
324 (113)
334 (50)
380 (30)
376 (8); 488 (10)
380 (2); 520 (3)
388 (3); 498 (40)
378 (60)
488 (50)
520 (30)
498 (80)
Properly understanding the luminescent properties of the
target compounds required examination of their fluores-
Figure 4. Normalized emission spectra at λexc = 360 nm for 1–4 in CH2Cl2.
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D. Collado, E. Perez-Inestrosa
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Figure 5. Absorption (Ϫ) and excitation spectra at λem = 380 (– –) and 520 (- -) nm for 3 in CH2Cl2.
cence excitation spectra recorded by monitoring the fluores- in local charges between the donor and acceptor sites. The
cence of their LE states. The fluorescence spectra thus ob- geminate pair can undergo three different processes,
tained are consistent with the corresponding absorption namely: (1) return ET to regenerate the ground-state com-
spectra for 1–4. These excitation spectra echo the main plex, (2) separation to form a separate cation radical and
spectral features of the ground-state absorption spectra for radical, and (3) fragmentation of the N–O bond to form a
1–4 (Figure S3). However, the fluorescence excitation spec- methoxy radical and a neutral heterocycle.[6a] The charge-
tra obtained by monitoring at the respective CT-emission shift process is a suitable driving force for methoxy radical
wavelength for each compound contained a CT band in the transfer.[1e,1f]
ground state for the dyads of 1–4 that is unnoticeable in the
Interesting aspects of the photochemistry of isoquinolin-
absorption spectra. Thus, the CT band of 1 in the ground ium salts have been communicated previously. The irradia-
state is virtually imperceptible (Figure 1). The absorption tion of N-ethoxyisoquinolinium salts has been described to
signal in the 340–420 nm region for 3 (Figure 5, solid line) cause homolytic N–OEt bond cleavage with a quantum
is suggestive of the appearance of an adsorption band con- yield of 0.48 and a rate constant of 1.5ϫ109 s–1 in
sistent with the excitation spectrum (Figure 5, dashed line) CH2Cl2.[11] The cation radical of isoquinoline (IQ·+) is a
at λem = 520 nm because of the increased electron-donating powerful oxidant (the oxidation potential of IQ·+ is 1.84 V
ability.
vs. SCE) and reacts rapidly with H2O (9.3ϫ105 Lmol–1 s–1)
and MeOH (1.4ϫ106 Lmol–1 s–1). Our preliminary studies
on the photochemical behaviour of covalently linked ac-
ceptor–donor systems based on isoquinoline N-oxide re-
vealed two main pathways: deoxygenation and hydroxyl-
ation.[4] The irradiation of 1–4 under the same conditions
(0.1 m in CH2Cl2, λ Ͼ 320 nm) yielded the corresponding
isoquinoline derivatives (deoxygenation process) and the
parent methoxylated compounds. Table 2 summarizes the
results of photochemical investigations in this respect. Pho-
tolysis of 5 gave the parent isoquinoline 15 and the meth-
oxylated products 16 and 17[12] (Table 2). In CH2Cl2, pho-
toproducts 16 and 17 were obtained by the insertion of a
methoxy radical in the 3- and 4-positions of the isoquin-
oline ring, respectively. No other photoproducts were de-
tected. The irradiation of 1 under the same conditions
yielded two methoxylated compounds in the 7- and 8-posi-
tions of the isoquinoline ring. A comparison with the pho-
Photochemical Reactivity
N-Methoxyisoquinolinium salts are strong one-electron
acceptors that are used as effective initiators for cationic
polymerizations,[8] which undergo photochemical N–O
bond cleavage to give isoquinoline cation radicals and an
alkoxy radical.[9] In solution, the addition of a suitable elec-
tron-donor moiety to an N-methoxyisoquinolinium salt re-
sults in the reversible formation of a CT complex, which
exhibits a broad CT electronic absorption that tails into the
visible region.[8,10] Excitation into this CT absorption band
results in the formation of the first excited state of the CT
complex, i.e. a geminate radical cation/radical pair. The ge-
neral photophysical process initially involves the transfer of
positive electronic charge from the isoquinolinium ring to
the phenyl substituent without alteration of the difference
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C–OMe Bond Formation and N–OMe Bond Fragmentation
toproducts of 5 revealed that these compounds are related Solvent Effects
to the photochemical behaviour of the N-methoxyisoquin-
Although the formation of methoxylation products was
olinium chromophore. Photolysis of 2, which possesses a
unique methoxy substituent in the electron-donor moiety,
gave a single photoproduct 10, the structure of which was
unequivocally assigned by comparison of its spectroscopic
data with those of an authentic sample.[4a] The irradiation
of 3 gave the photoproduct 12, which incorporates a meth-
oxy group in the electron-donor ring. Both 3 and 4 exhibit
the same substitution in the donor component. Photolysis
of 4 gave the methoxylated regioisomers expected from the
behaviour of 3 described above. Compounds 10, 12 and 14
were formed as a result of the insertion of a methoxy radi-
cal into the electron-donor component and show that the
methoxylation photoprocess can occur by two different
pathways. One involves direct N–O bond scission and cou-
pling of the methoxy radical, and the other is governed by
ET from the donor to the acceptor moiety, consistent with
the formation and coupling of the methoxy radical. The
overall process is the methoxylation of the electron-donor
or -acceptor component.
observed in CH2Cl2, the methoxylation yields were low
(Table 2). Attempts to improve the yields were made by ir-
radiation in a more polar solvent. Irradiation in aqueous
media led to the formation of the same photoproducts. In
general, H2O increased the formation of the methoxylated
compounds by a factor of four in 4 (Table 3).[13] However,
radicals may either diffuse out of the solvent cage or recom-
bine within the cage. The influence of viscosity on the gemi-
nate recombination of paired radicals has been extensively
studied, and the extent of the cage reaction has been found
to increase with increasing viscosity.[14] Increased viscosity
is known to reduce the mobility of radicals and increase the
recombination efficiency of radical cage pairs. Accordingly,
we used a 1:1 (v/v) mixture of H2O/glycerine to increase the
viscosity of the medium. As expected, this increased the
yields of the methoxylated photoproducts of 2–4 (Table 3).
The improvement, however, was only moderate. The fact
that photoproduct yields depend on the polarity and vis-
cosity of the solvent testifies to the importance of the radi-
cal coupling step in the photoprocess.
Table 2. Photoproducts and yields of isolated compounds obtained
by the irradiation of 1–5 at a 10–3 m concentration in CH2Cl2.
Table 3. Methoxylation yields [%] in CH2Cl2, H2O and a 1:1 H2O/
glycerine mixture.
10
12
14
CH2Cl2
H2O
H2O/glycerine
15
24
31
5
19
26
6
21
35
Mechanistic Considerations
Photolytic cleavage of the N–O bond in N-methoxyphen-
anthridinium perchlorate occurs homolytically and pro-
duces a methoxy radical that undergoes intermolecular
methoxylation in the presence of monosubstituted benz-
ene.[14] Our systems exhibit the effective formation of C–
OMe bonds to give new molecules with a methoxy substitu-
ent in the electron-donor moiety under irradiation.
Our systems exhibit two different photochemical path-
ways (Scheme 4), namely: insertion of a methoxy group into
the electron-acceptor (intercomponent methoxylation) or
electron-donor moiety (intracomponent methoxylation).
Both pathways are initiated by N–O bond scission, but one
starts with ET as inferred from spectroscopic data for 2–4.
One-electron transfer to an N-isoquinolinium chromophore
results in N–O bond cleavage and the formation of an alk-
oxy radical. Insertion into the donor moiety causes inter-
component transfer of the methoxy group as shown in
Scheme 4. The position of the new methoxy group in the
electron-donor moiety depends on the substituents on the
benzene ring. It is dictated by the cation radical derived
from the donor moiety upon ET and is consistent with the
reported spin densities for the model compounds. The inter-
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D. Collado, E. Perez-Inestrosa
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Scheme 4.
component methoxylation process is an example of re- hydrogen abstraction, (4) disproportionation, (5) rearrange-
ductive cleavage. The driving force for the fragmentation ment, and (6) decomposition. Only in the first and second
reaction in this case is rearomatization to a more stable iso- classes is the structure of the alkoxyl radical preserved in
quinoline ring.[4a]
the end product. With the methoxy radical, disproportiona-
The second pathway, intracomponent methoxylation, in- tion produces CH3OH and H2C=O. This reaction involves
volves the transfer of the methoxy group from the N-posi- the formation of a double bond and is thus more exother-
tion to the 3- or 4-position of the isoquinoline chromo- mic than hydrogen abstraction. Unimolecular rearrange-
·
phore and results from coupling between the cation radical ment of methoxy radicals CH3O· Ǟ CH2OH, is also exo-
isoquinoline ring and the methoxy radical. This is the main thermic. The height of the barrier to isomerization is
photochemical pathway for 5. The results for 1 are worth 5 kJmol–1, which is lower in polar solvents but still high
special note; thus, its photoreactivity is basically also due enough (ca. 133 kJmol–1) to make CH3O· kinetically stable.
to its chromophore but differs from that of 2–4. As a result, The decomposition reaction implies the formation of a
no ET is apparent in the fluorescence spectra, and the do- carbonyl compound, CH3O· Ǟ H2C=O + H·, with a disso-
nor does not take part in the photochemical reaction. ciation energy of 20.1 kcalmol–1.[20] Irradiation of N-meth-
Therefore, N–O scission does not result from the initial ET. oxyphenenthridinium perchlorate in the absence of a donor
However, it produces an alkoxy radical and a cation radical produces phenanthridine, methanol and formaldehyde di-
in the isoquinoline ring, recombination of which leads to methyl acetal from the decomposition of the methoxy radi-
the insertion of a methoxy group in the 3- or 4-position of cal. Rearrangement was not observed in any case.[15a] The
the isoquinoline ring (Scheme 4). The redox potential of the photolysis of N-ethoxyquinolinium perchlorate in methanol
electron donor can be altered (e.g. by changing the number gives quinoline, 2-quinolinemethanol and 4-quinolinemeth-
of methoxy substituents) to control its chemical reactivity anol. These compounds result from hydrogen atom abstrac-
in order for it to respond to irradiation with reductive or tion from the solvent, methanol, by the ethoxy radical, fol-
homolytic bond cleavage. In both cases, a methoxy radical lowed by reaction of the resulting methanol radical.[15b] The
forms during the photolysis of 1–4. The radical is the sim- insertion of methanol was not observed in 1–4. As in the
plest member of the alkoxy radicals series, RO·, and takes irradiation of N-methoxyphenenthridinium, decomposition
part in many important reactions.[16] These radicals are in- of the methoxy radical (6) can boost the formation of de-
termediates in the pyrolysis and photolysis of a variety of oxygenating compounds (the parent isoquinolines 6, 9, 11,
organic peroxides and esters and in the decomposition of 13 and 15). However, no significant difference in photod-
explosives. Under physiological conditions, cells produce eoxygenation yields was observed in solvents of variable po-
oxygen radicals during oxygen metabolism and other redox larity and viscosity. The chemical behaviour of the methoxy
reactions, which are crucial for many biological func- radical has no crucial effect on the formation of photoprod-
tions.[17,18] The reactions undergone by alkoxy radicals can ucts. In 2–4, the photochemical reaction is controlled by the
be classified into six groups, namely:[19] (1) association with donor moiety and leads to a CT state that is responsible for
other radicals, (2) addition to unsaturated compounds, (3) intercomponent methoxylation.
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C–OMe Bond Formation and N–OMe Bond Fragmentation
minimum amount of chloroform and subjected to column
chromatography with hexane/ethyl acetate (from 4:1 to 1:1) as the
mobile phase. The photodeoxygenated products (6, 9, 10, 11, 13,
Conclusions
The structure of molecules that take part in ET processes
is often altered to the extent of causing bond dissoci- 15, 16) were identified by comparison with pure samples synthe-
sized in accordance with a previously reported procedure.[4a]
ation.[21] Competitive coupling of ET and bond cleavage
can take place by concerted or stepwise pathways.[22] The
concerted pathway is the only feasible choice in the absence
of an intermediate cation radical, but the stepwise pathway
may not occur even in its presence. In any case, the reaction
proceeds by the energetically most favourable pathway. The
bichromophoric AsD systems studied here take part in two
photochemical processes: intercomponent and intracom-
ponent methoxylation. Homolytic N–OMe bond fragmen-
tation upon irradiation is a characteristic process of this
group. However, the overall photoprocess in the AsD sys-
tems studied is controlled by the donating ability (redox
potential) of the donor subunit. N–OMe bond fragmenta-
tion in the radicals formed by the one-electron reduction of
N-methoxyisoquinolinium compounds results in the aro-
matic photomethoxylation of the electron-donor moiety.
This radical process is regioselectively guided by the resid-
ual spin density of the resulting cation radical on the elec-
tron-donor component. On the other hand, intracompon-
ent methoxylation is the intrinsic photochemical behaviour
of the N-methoxyisoquinolinium chromophore. The inser-
tion pathway for the reacting radicals can be adjusted by
the donating ability (i.e. the redox potential). This is consis-
1-Benzyl-4-methoxyisoquinoline (7): Colourless oil. Rf = 0.7 (Ac-
1
OEt/hexane, 1:1). H NMR (CDCl3): δ = 4.05 (s, 3 H), 4.57 (s, 2
H), 7.13–7.24 (m, 5 H), 7.51 (t, J = 8.5, 1.9 Hz, 1 H), 7.62 (t, J =
8.2, 1.3 Hz, 1 H), 8.03–8.06 (m, 2 H), 8.20 (d, J = 8.7 Hz, 1 H)
ppm. 13C NMR (CDCl3): δ = 41.5, 55.9, 103.8, 119.6, 121.56,
121.68, 122.7, 125.5, 126.1, 127.5, 128.4, 128.5, 129.1, 139.8, 140.0,
149.7, 152.4 ppm. MS: m/z (%) = 249 (35) [M]+, 248 (100). HRMS
(FAB): calcd. for C17H15NO3 [M]+ 249.1154; found 249.1156.
1-Benzyl-3-methoxyisoquinoline (8): Colourless oil. Rf
= 0.7
1
(AcOEt/hexane, 1:1). H NMR (CDCl3): δ = 4.00 (s, 3 H), 4.58 (s,
2 H), 6.86 (s, 1 H), 7.11–7.32 (m, 6 H), 7.49 (t, J = 6.8, 1.2 Hz, 1
H), 7.66 (d, J = 8.2 Hz, 1 H), 8.05 (d, J = 8.1, 1.0 Hz, 1 H) ppm.
13C NMR (CDCl3): δ = 41.5, 54.3, 99.0, 121.0, 123.8, 124.3, 125.83,
126.2, 126.4, 127.6, 127.9, 128.4, 128.7, 129.9, 131.0, 141.3,
152.6 ppm. MS: m/z (%) = 249 (61) [M]+, 248 (100), 233 (23).
HRMS (FAB): calcd. for C17H15NO3 [M]+ 249.1154; found
249.1159.
1-(2,4,5-Trimethoxybenzyl)isoquinoline (12): Solid. M.p. 110–
111 °C. Rf = 0.13 (AcOEt/hexane, 3:7); 1H NMR (CDCl3): δ = 3.61
(s, 3 H), 3.83 (s, 3 H), 3.88 (s, 3 H), 4.58 (s, 2 H), 6.54 (s, 1 H),
6.64 (s, 1 H), 7.46–7.54 (m, 2 H), 7.53 (t, J = 6.7 Hz, 1 H), 8.24 (d,
J = 7.9 Hz, 1 H), 8.44–8.49 (m, 2 H) ppm. 13C NMR (CDCl3): δ
= 40.7, 54.6, 56.1, 56.3, 112.9, 116.2, 120.2, 125.2, 126.0, 127.9,
tent with the emission observed upon excitation of the CT 130.7, 136.1, 141.6, 157.7, 158.1 ppm. MS: m/z (%) = 309 (4)
[M]+, 279 (21), 278 (100). HRMS (FAB): calcd. for C19H19NO3
state in systems that exhibit intermethoxylation, where
methoxy group transfer from the acceptor to the donor is
[M]+ 309.1365; found 309.1369.
the energetically most favourable pathway.
1-(2,4,5-Trimethoxybenzyl)-6,7-dimethoxyisoquinoline (14): Solid.
M.p. 128–129 °C. Rf = 0.35 (CH2Cl2/MeOH, 9.6:0.4). 1H NMR
(CDCl3): δ = 3.63 (s, 3 H), 3.83 (s, 3 H), 3.89 (s, 3 H), 3.92 (s, 3
H), 3.97 (s, 3 H), 4.50 (s, 2 H), 6.53 (s, 1 H), 6.73 (s, 1 H), 6.99 (s,
1 H), 7.38 (d, J = 5.5 Hz, 1 H), 7.55 (s, 1 H), 8.32 (d, J = 6.1 Hz,
1 H) ppm. 13C NMR (CDCl3): δ = 34.1, 55.8, 56.0, 56.1, 56.3, 56.9,
97.6, 104.6, 105.0, 113.7, 118.7, 118.9, 122.8, 133.5, 139.8, 143.3,
148.1, 149.9, 152.8, 158.4 ppm. MS: m/z (%) = 369 (23) [M]+, 338
(100), 280 (39). HRMS (FAB): calcd. for C21H23NO5 [M]+
369.1576; found 369.1581.
Experimental Section
General Methods: All starting material and reagents were used as
received. Solvents were spectrophotometric or HPLC grade and
1
used without further purification. H and 13C NMR spectra (200
and 50 MHz, respectively) were recorded from CDCl3 solutions by
using the solvent residual proton signal as standard. TLC analyses
were performed with silica gel 60 F256 plates, and column
chromatography was carried out with silica gel 60 (70–230 mesh).
Melting points were obtained in open capillaries. Samples for UV/
Vis and emission spectra were prepared in spectroscopic grade sol-
vents and adjusted to a linear range response. Molar absorption
coefficients were determined by using compound concentrations of
10–4 or 10–5 m. No fluorescent contaminants were detected upon
excitation in the wavelength region of experimental interest.
Fluorescence quantum yields were determined by comparison with
0.1 m quinine sulfate in 0.5 m sulfuric acid as a reference (Φ =
0.546)[23] and corrected for the refractive index of the solvent. The
samples were prepared with an absorbance between 0.1 and 0.2
a.u. at the excitation wavelength.
Supporting Information (see footnote on the first page of this arti-
cle): Details of the synthesis and photolysis studies of 1–5; UV
spectra and fluorescence emission/excitation spectra of compounds
1–5.
Acknowledgments
The authors wish to acknowledge funding from Spain’s Ministerio
de Ciencia
e Innovación and FEDER contribution (Project
CTQ2010-20303).
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Published Online: February 3, 2012
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Eur. J. Org. Chem. 2012, 1800–1808