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H.-M. Zhou et al. / Journal of Photochemistry and Photobiology A: Chemistry 246 (2012) 60–66
and flash chromatography and obtained as a white powder (210 mg,
85%). 6 (104 mg, 0.25 mmol) was refluxed in acetone (10 mL) in
the presence of NaI (100 mg, 0.67 mmol) for 5 h. The mixture
was diluted with water and extracted with EtOAc twice. The
organic layers were dried with Na2SO4, filtered, and concentrated
in vacuo. The 2-iodoethyl-dimer product 7 was obtained as light
yellow powder (92 mg, 80%). Cs2CO3 (163 mg, 0.50 mmol) and 2-
chlorophenothiazine (70 mg, 0.30 mmol) were added to a solution
of 7 (92 mg, 0.20 mmol) in DMF (2 mL) and the reaction was stirred
overnight at room temperature. The mixture was diluted with
water and extracted with EtOAc for 3 times. The organic layers were
dried with Na2SO4, filtered, and concentrated in vacuo. The residue
was subjected to flash chromatography (silica gel-H, petroleum
ether/EtOAc = 1/0→1/4). The product was recrystallized from
O
N
O
N
O
N
O
N
N
N
N
N
O
O
O
O
hv (340 nm)
( )n
N
( )n
N
R
R
S
S
1a 1c
3a 3c
Fig. 2. Photosensitized splitting reactions of dimer unit of model compounds under
irradiation with 340 nm light.
methanol as a white powder (20 mg, 18%). M.p. 196.4–201.8 ◦C; 1
H
NMR (300 MHz, CDCl3): ı = 1.29 (s, 3H, CH3), 1.42 (s, 3H, CH3), 1.62
(m, 1H), 2.38 (m, 1H), 2.87 (s, 3H, NCH3), 2.97 (m, 1H), 3.68 (d,
J = 7.0 Hz, 1H, CH), 3.92 (d, J = 7.2 Hz, 1H, CH), 3.89–4.36 (m, 7H),
6.86–7.23 (m, 7H, Ar H); 13C NMR (75 MHz, CDCl3): ı = 18.4 (CH3),
18.7 (CH3), 22.9, 36.4, 41.7, 41.8, 43.1, 45.2, 50.8 (C), 51.7 (C), 60.0
(CH), 60.7 (CH), 116.1, 116.2, 123.4, 124.0, 124.2, 125.4, 128.1, 128.3,
128.7, 134.0, 144.2, 146.5, 151.9, 152.0, 170.2 (2C); HRMS (ESI-TOF)
calculated for C28H29ClN5O4S [M+H]+ 566.1623, found 566.1617.
Model compound 1b: 2-Chlorophenothiazine (500 mg,
2.2 mmol) and 1,3-dibromopropane (4 mL, 39 mmol) were added
to a suspension of 50% NaOH solution (5 mL), TBAB (0.15 g,
0.47 mmol) and toluene (5 mL), and the reaction was stirred at
room temperature for 3.5 h. The mixture was diluted with water
and extracted with EtOAc. The organic layers were dried with
Na2SO4, filtered and concentrated in vacuo. The residue was
purified by flash chromatography to obtain 1-(3-bromopropyl)-
2-chlorophenothiazine as light yellow oil (160 mg, 21%). Sodium
t-butoxide (40 mg, 0.4 mmol) was added to the solution of cis,
syn-thymine dimer 5 (62 mg, 0.20 mmol) in DMF (3 mL) and the
reaction was stirred at room temperature for 30 min. The above oil
(160 mg, 0.45 mmol) was added, and then the stirring was resumed
overnight at room temperature. The mixture was diluted with
water and extracted with EtOAc. The organic layers were dried with
Na2SO4, filtered, and concentrated in vacuo. The crude residue was
subjected to flash chromatography (silica gel-H, EtOAc/petroleum
ether = 3/2→3/1). The product was recrystallized from methanol
as a white powder (83 mg, 72%). M.p. 157.4–159.6 ◦C; 1H NMR
(300 MHz, CDCl3): ı = 0.78 (s, 3H, CH3), 1.31 (s, 3H, CH3), 1.55 (m,
1H), 2.18 (m, 1H), 2.34 (m, 1H), 2.72 (m, 1H), 2.89 (s, 3H, NCH3),
3.64 (d, J = 7.2 Hz, 1H, CH), 3.76 (d, J = 7.2 Hz, 1H, CH), 3.80–4.25 (m,
7H), 6.89–7.28 (m, 7H, Ar H); 13C NMR (75 MHz, CDCl3): ı = 17.6
(CH3), 18.7 (CH3), 22.9, 24.7, 36.4, 41.5, 41.8, 43.4, 45.3, 50.6 (C),
50.7 (C), 60.2 (CH), 60.8 (CH), 117.1, 117.2, 123.5, 124.1, 124.8,
126.1, 128.1, 128.3, 128.6, 134.2, 144.7, 146.5, 151.8, 152.1, 170.1,
170.5; ESI-MS: [M+H]+ = 580.4; HRMS (ESI-TOF) calculated for
3H), 2.88 (s, 3H, NCH3), 2.76 (m, 1H), 3.65 (d, J = 7.0 Hz, 1H, CH),
3.82 (d, J = 7.2 Hz, 1H, CH), 3.83–4.18 (m, 7H), 6.91–7.29 (m, 8H,
Ar H); 13C NMR (75 MHz, CDCl3): ı = 17.3 (CH3), 18.5 (CH3), 22.7,
24.6, 36.2, 41.7, 41.8, 45.7, 46.4, 50.4 (C), 50.5 (C), 59.9 (CH), 60.6
(CH), 116.8 (4C), 123.4 (2C), 126.3, 127.9 (4C), 146.5, 151.7, 152.0,
170.1, 170.4; HRMS (ESI-TOF) calculated for C29H32N5O4S [M+H]+
546.2168, found 546.2167.
3. Results and discussion
3.1. Synthesis of the model compounds 1a–1c
Three model compounds were synthesized from the cis–syn
thymine dimer [10] via the routes depicted in Scheme 1. The
N-alkylation of cis–syn thymine dimer 5 was reacted with 1,2-
dibromoethane in DMF to yield 2-bromoethyl-dimer 6, which was
converted to 2-iodoethyl-dimer 7 as light yellow powder by the
Finkelstein reaction. The model compound 1a was obtained by
the reaction of 7 with 2-chlorophenothiazine in the presence of
cesium carbonate. The model compounds 1b and 1c were prepared
from cis–syn thymine dimer 5 alkylated with the corresponding 1-
(3-bromopropyl)-2-chloro-phenothiazine and 1-(3-bromopropyl)
phenothiazine in 72% and 78% yield respectively. The N-alkylation
of phenothiazine (or 2-chlorophenthiazine) with excessive 1,3-
dibromopropane was carried out through tetrabutyl ammonium
bromide (TBAB) as phase-transfer catalyst in toluene/water sol-
vent. The synthesis of compounds 4a, 4b and 3c is presented in
Supporting Information.
3.2. Photosplitting properties of the model compounds
The model compounds 1a–1c in methanol solution was irradi-
with a 125 W Xe lamp passed through a monochromator. Analysis
of the photolysis mixture by reverse-phase HPLC confirmed that
the model compounds react cleanly to give 3a, 3b and 3c from 1a,
1b and 1c respectively (Fig. 2).
Furthermore, the expected photoproduct 3c was synthesized
and identified by NMR and HPLC co-injection. A representative
set of HPLC chromatograms showing the simultaneous splitting
of model 1c into 3c was depicted in Fig. 3. Obviously, the split-
ting reaction of model 1c, with retention time of 5.2 min, to the
photosplitting product 3c, with retention time of 5.7 min, is clean
conversion as no other products could be detected.
C
29H31ClN5O4S [M+H]+ 580.1780, found 580.1776.
Model compound 1c: Compound 1-(3-bromopropyl)
phenothiazine was synthesized in a similar procedure through
phenothiazine instead of 2-chlorophenothiazine, and obtained
as light yellow oil (150 mg, 23%). Sodium t-butoxide (40 mg,
0.4 mmol) was added to the solution of cis, syn-thymine dimer 5
(80 mg, 0.26 mmol) in DMF (4 mL) and the reaction was stirred at
room temperature for 30 min. The above oil (150 mg, 0.47 mmol)
was added, and then the stirring was resumed overnight at room
temperature. The mixture was diluted with water and extracted
with EtOAc. The organic layer was dried with Na2SO4, filtered,
and concentrated in vacuo. The residue was subjected to flash
chromatography with silica-H absorbent (CHCl3→EtOAc). The
product was recrystallized from methanol as a white powder
(110 mg, 78%). M.p. 194.2–197.8 ◦C; 1H NMR (300 MHz, CDCl3):
ı = 0.70 (s, 3H, CH3), 1.30 (s, 3H, CH3), 1.54 (m, 1H), 2.05–2.43 (m,
3.3. Fluorescence emission spectra
Fig. 4 showed the fluorescence emission spectra of mod-
els 1a–1c and the free phenothiazine (either N-methyl-
2-chlorophenothiazine 4a or N-methyl-phenothiazine 4b) in