Photochemistry and Photobiology, 2014, 90 315
Compounds 1/1E, 2/2E, 3/3E, 4/4E and 6/6E were available from
previous studies (41). The N-methoxy structures 1–8 were all prepared as
tetrafluoroborate salts, the corresponding N-ethyl structures (1E–8E) were
prepared as either tetrafluoroborate or hexafluorophosphate salts.
General synthetic procedures: The other N-ethyl- and N-methoxyhet-
erocycles (5/5E, 7/7E, 8/8E) were prepared by alkylation of the corre-
sponding heterocycles and their N-oxides. The general procedures for the
alkylations and preparation of the N-oxides have been described previ-
ously (41). The synthesized products were characterized by proton and
carbon NMR spectroscopy using the Varian Gemini 300, Varian Inova
400 and Varian Inova 500 spectrometers. The samples were dissolved in
CDCl3, DMSO-d6, CD3CN, or CD3OD (Cambridge Isotopes). Mass veri-
fication was accomplished using a Vestec MALDITOF mass spectrometer
with 337 nm excitation; the compounds were sometimes excited without
a matrix (LD-TOF).
(ppm) = 4.46 (s, 3H), 7.68 (t, 2H, J = 7.82 Hz), 7.92 (t, 1H,
J = 7.57 Hz), 8.03–8.08 (m, 3H), 8.19 (d, 1H, J = 8.30 Hz), 8.29–8.33
(m, 2H), 8.49 (t, 1H, J = 7.82 Hz), 8.57 (d, 1H, J = 8.66 Hz), 9.17
(t, 2H, J = 9.5 Hz). 13C NMR (125.718 MHz, CD3CN)
d
(ppm) = 71.96, 118.75, 122.83, 125.13, 126.02, 129.14, 130.84, 131.15,
131.51, 132.60, 132.62, 133.27, 134.55, 134.75, 136.78, 138.33, 140.19,
154.77, 185.53. MS m/z 314.1 (M+)
N-ethyl-6-benzoylphenanthridine tetrafluoroborate (8E): Preparation of
8b was performed according to the procedure outlined above. Alkylation
of 6-benzoylphenanthridine, 8b, (0.365 g, 1.29 mmol) was performed
according to the general procedures, affording 0.36 g (0.89 mmol, 69%)
of 8E. 1H NMR (399.86 MHz, CD3CN)
d (ppm) = 7.64 (t, 2H,
J = 7.3 Hz), 7.87 (t, 1H, J = 7.5 Hz), 7.87 (t, 1H, J = 7.5 Hz), 7.98
(d, 3H, J = 8.4 Hz), 8.14 (m, 2H), 8.27 (m, 2H), 8.39 (t, 1H,
J = 7.8 Hz), 9.03 (m, 1H), 9.09 (d, 1H, J = 8.5 Hz). 13C NMR
(125.718 MHz, CD3CN) d (ppm) = 123.02, 123.60, 124.80, 124.90,
126.86, 130.53, 131.21, 131.58, 131.80, 132.36, 133.31, 135.56, 137.49,
137.59, 139.09. MS m/z 314.08 (M+)
Measurement methods and instrumentation. Nanosecond and picosec-
ond transient absorption spectroscopy was performed as described previ-
ously (41). Emission spectroscopy was performed using a Spex
N-methoxy-2-(4′-methoxystyryl) pyridinium tetrafluoroborate (5):
Following the literature procedure (41), 2-(4′-methoxystyryl) pyridine N-
oxide (1.40 g, 6.16 mmol, synthesized according to (41)) and trim-
ethyloxonium tetrafluoroborate (1.05 g, 7.08 mmol) were stirred in
50 mL dichloromethane. The precipitate was filtered off and yielded
1.49 g (4.53 mmol, 73%) of 5. 1H-NMR (300 MHz, CD3CN)
d
(ppm) = 3.74 (s, 3 H), 4.19 (s, 3 H), 6.88–6.93 (m, 3 H), 7.23 (d, 1H,
J = 16.5 Hz), 7.59–7.66 (m, 3 H), 7.81 (d, 1 H, J = 16.5 Hz), 8.17–8.25
(m, 1 H), 8.62 (d, 1 H, J = 7.2 Hz). 13C-NMR (75 MHz, CD3CN) d
(ppm) = 56.2, 70.0, 110.8, 115.6, 126.1, 126.5, 131.3, 131.7, 141.0,
144.3, 146.2, 151.6, 163.5. MS m/z 242.4 (M+).
N-ethyl-2- (4′-methoxystyryl)pyridinium hexafluorophosphate (5E):
Following the general procedure (41), 2-(4′-methoxystyryl)pyridine
(1.80 g, 8.52 mmol) and triethyloxonium hexafluorophosphate (2.56 g,
10.3 mmol) were stirred in 40 mL of dichloromethane. Recrystallization
from methanol/dichloromethane afforded 2.49 g (6.46 mmol, 75%) of
5E. 1H-NMR (300 MHz, CD3CN) d (ppm) = 1.53 (t, 3 H, J = 7.2 Hz),
3.85 (s, 3 H), 4.63 (q, 2 H, J = 7.2 Hz), 7.00–7.04 (m, 2 H), 7.22 (d, 1
H, J = 15.9 Hz), 7.72 (d, 1 H, J = 15.9 Hz), 7.73–7.76 (m, 3 H), 8.22–
8.34 (m, 2 H), 8.50 (d, 1H, J = 6.0 Hz).
N-methoxy-1-isoquinolinyl phenyl ketone tetrafluoroborate (7): Fol-
lowing the general procedures (41), trimethyloxonium tetrafluoroborate
(0.27 g, 1.83 mmol) and 1-isoquinolinyl phenyl ketone N-oxide (0.40 g,
1.58 mmol, synthesized according to the general procedures (41)) were
stirred in minimum amount of dichloromethane to dissolve the reactants,
and allowed to react for 4 h. Recrystallization from a methanol/ethyl
acetate mixture afforded .49 g (1.39 mmol, 88%) of 7. 1H NMR
Fluorolog 1-1-2 spectrometer. Spectra at room temperature were mea-
sured in 1 cm pathlength cuvettes with arms that could be sealed with
stopcocks, if necessary, after deoxygenation by purging with argon.
Experiments at liquid nitrogen temperature were performed by immer-
sion of the samples, contained in NMR tubes that had been sealed after
purging with argon, into a specially designed Dewar that fitted the stan-
dard sample compartment of the fluorimeter. Samples for study at liquid
nitrogen temperature were prepared in either an EPA solution (a 2:5:5
mixture of ethanol:isopentane:diethyl ether), or a 50:50 mixture of etha-
nol and methanol with 1.0 M methyl iodide, as indicated in the figure
captions.
The reduction potentials for 7E and 8E were estimated using cyclic
voltammetry (CV) in acetonitrile at room temperature, in the presence of
0.1 M LiClO4 as electrolyte and with 1 mM of the analyte, using a CHI
900C potentiostat. Solutions were purged with N2 for 10 min. Ag/AgCl
was used as a reference electrode and Pt wire was used as a counter elec-
trode. The working electrode was a glassy carbon disk of surface area
0.07065 cm2. CV experiments were done at a scan rate of 5 V/s. Highly
reversible reduction was observed for 7E, but 8E was not reversible. The
reduction potential for 8E was thus estimated by adding 0.17 V to the lit-
erature potential for 3E, as this is the observed potential difference
between 1E and 7E. As described in the text, the reduction potentials for
all of the N-methoxy structures were then estimated from those for the
corresponding N-ethyl structures by adding 0.14 V (37).
Product Analysis: 25 mg of N-methoxyquinolinium tetrafluoroborate
(1) was dissolved in 25 mL of acetonitrile and purged with nitrogen. Irra-
diation was performed in a Luzchem photoreactor with UV-B lamps until
no starting material could be detected (by TLC). Aqueous sodium bicar-
bonate solution was added to the irradiated solution, which was then
extracted with methylene chloride. The organic layer was dried over
magnesium sulfate and filtered.
GC-MS analysis was performed using a Shimadzu GCMS QP5000
with a Restek RTX-XLB (Cat #12823) column. A typical temperature
program was 11°C/min from 125 to 250°C, with an initial hold time of
8 min and a final hold time of 30 min. The retention times were 6.5 min
for quinoline and between 13.1 and 13.6 min for methoxylated quino-
lines. The mass spectra were matched with the NIST/EPA/NIH Mass
Spectral Library 2002.
(499.92 MHz, CD3CN)
d
(ppm) = 4.50 (s, 3H), 7.59 (t, 2H,
J = 7.9 Hz), 7.81 (t, 1H, J = 8.0 Hz), 8.00 (d, 2H, J = 7.9 Hz), 8.04–
8.11 (m, 2H), 8.31 (t, 1H, J = 8.0 Hz), 8.53 (d, 1H, J = 8.0 Hz), 8.91
(d, 1H, J = 7.5 Hz), 9.29 (d, 1H, J = 7.0 Hz). 13C NMR (125.718 MHz,
CD3CN)
d (ppm) = 42.63, 98.31, 100.11, 101.18, 102.07, 102.25,
102.85, 104.35, 105.49, 106.66, 109.36, 110.15, 110.80, 185.6. MS m/z
264.04 (M+).
N-ethyl-1-isoquinolinyl phenyl ketone tetrafluoroborate (7E): Follow-
ing the general procedure (41), triethyloxonium tetrafluoroborate (3.0 g,
15.8 mmol) and 1-isoquinolinyl phenyl ketone (3.2 g, 13.7 mmol) were
stirred in minimum amount of dichloromethane to dissolve the reactants,
and allowed to react for 4 h. Recrystallization from a methanol/ethyl ace-
tate afforded 3.6 g (10.4 mmol, 76%) of 7E. 1H NMR (499.92 MHz,
CD3CN) d (ppm) = 1.60 (t, 3H, J = 7.0 Hz), 4.69 (m, 1H, J = 6.9 Hz),
4.85 (m, 1H, J = 6.9 Hz), 7.60 (t, 2H, J = 7.8 Hz), 7.83 (tt, 1H, J = 1.1,
7.5 Hz), 7.96–8.02 (m, 4H), 8.27 (m, 1H), 8.45 (d, 1H, J = 8.0 Hz),
8.79 (d, 1H, J = 7.0 Hz), 8.99 (d, 1H, J = 6.5 Hz),. 13C NMR
(125.718 MHz, CD3CN) d (ppm) = ꢀ11.7, 28.0, 98.3, 100.3, 100.4,
100.8, 102.4, 103.1, 104.8, 106.8, 108.4, 109.6, 109.9, 111.0, 185.6. MS
m/z 262.10 (M+).
Proton Yield Measurements: N-methoxyheterocycle tetrafluoroborate
(~25 mg, 0.1 mmol) was irradiated in 25 mL of nitrogen-purged solvent
as described above until complete consumption of the starting material
was observed by TLC. The pH of the resulting solution was measured
using three methods. Method A: Appropriately diluted aliquots of the
solution were mixed with a phosphate buffer solution (3 mM, pH ~ 7.6)
and the pH was then measured. The change in pH relative to a reference
sample yielded the protons produced in the irradiation sample. The same
procedure was performed with a TRIS buffer (3 mM, pH ~ 8.3). Method
B: Spectrophotometric analysis of methanolic p-nitrophenolate solutions
(kmax = 400 nm) (53) with and without exposure to aliquots of the irradi-
ation solution was used to calculate the concentration of the photogener-
ated protons. Method C: The N-methoxyheterocycle was dissolved in a
buffer solution (phosphate buffer ~3 mM, pH ~ 7.6, or TRIS buffer
~3 mM, pH ~ 8.3), and the pH was constantly monitored during the
N-methoxy-6-benzoylphenanthridine tetrafluoroborate (8): 8 was pre-
pared from 6-benzyl-5,6-dihyrophenanthridine (8a), which was prepared
according to a literature procedure (50). 8a (0.813 g, 3.0 mmol) was dis-
solved in warm glacial acetic acid and excess Na2Cr2O7 was added over
30 min. The solution was refluxed for 90 min, poured into water and
cooled over night (51). Recrystalization from ethanol afforded 0.73 g
(2.58 mmol, 86%) of 6-benzoylphenanthridine (8b). Compound 8b,
0.365 g (1.29 mmol) was oxidized to the N-oxide using perbenzoic acid
(2.972 mmol) (52). The resulting emulsion was extracted with CHCl3 to
afford 0.33 g (1.11 mmol, 86%) 6-benzoylphenanthridine N-oxide (8c).
Alkylation was carried out according to the general procedures to yield
0.4 g (.99 mmol, 89%) of 8. 1H NMR (499.92 MHz, CD3CN)
d