Y. Zhou, et al.
JournalofPhotochemistry&PhotobiologyA:Chemistry384(2019)112033
phosphate buffer solution was stored in a MBRAUN Labmaster 130
(1250/78) glovebox equipped with O2 and H2O sensors under an argon
atmosphere.
as a yellow oil (0.90 g, 92%), which was pure and was directly used in
the next step. 1H NMR (400 MHz, DMSO-d6) δ 8.02 (dd, J = 8.0, 1.2 Hz,
1 H), 7.77-7.70 (m, 2 H), 7.56 (td, J = 8.0, 1.6 Hz, 1 H), 6.26 (s, 2 H),
4.89 (s, 2 H). 13C NMR (101 MHz, DMSO-d6) δ 147.69, 134.09, 133.48,
129.41, 128.40, 124.24, 73.08. HRMS m/z (DART) calculated for MH+
169.0608, found 169.0607.
5.2. Synthetic procedures and product characterization
5.2.1. 2-(2-Nitrobenzyloxy)isoindoline-1,3-dione (3a)
A solution of 2-nitrobenzyl bromide (2a) (5.01 g, 23.2 mmol) in
anhydrous DMF (40 mL) was added dropwise at room temperature to a
stirred solution of N-hydroxyphthalimide (4.15 g, 25.4 mmol) and N,N-
5.2.4. O-(4,5-Dimethoxy-2-nitrobenzyl)hydroxylamine (4b)
Hydrazine monohydrate (1.24 mL,
d =1.032 g/mL at 25 °C,
25.6 mmol) was added in one portion to a stirred solution of 3b
(3.780 g, 10.55 mmol) in anhydrous CH2Cl2 (120 mL) under N2 at room
temperature. The reaction mixture was stirred for 4 h at room tem-
perature. After the resulting white suspension was filtered off, the fil-
trate was washed with water (100 mL). The aqueous layer was ex-
tracted with CH2Cl2 (3 × 80 mL) and the combined organic extracts
were dried over MgSO4, filtered, and concentrated in vacuo. The title
compound 4b was obtained as a yellow oil (2.05 g, 85%), which was
pure and was directly used in the next step. 1H NMR (400 MHz, DMSO-
d6) δ 7.65 (s, 1 H), 7.19 (s, 1 H), 6.33 (s, 2 H), 4.90 (s, 2 H), 3.86 (s, 3 H),
3.85 (s, 3 H). 13C NMR (101 MHz, DMSO-d6) δ 153.18, 147.21, 139.35,
129.89, 110.26, 107.71, 73.36, 56.05, 55.90. HRMS m/z (DART) cal-
culated for MH+ 229.0819, found 229.0819.
diisopropylethylamine (DIEA, 4.43 mL,
d =0.742 g/mL at 25 °C,
25.4 mmol) in anhydrous DMF (60 mL) under N2. The reaction mixture
was heated to 70 °C (over 30 min) and was stirred for 2 h. The reaction
mixture was allowed to cool to room temperature and was then poured
into water (200 mL). The aqueous layer was extracted with ethyl
acetate (3 × 100 mL). A pale-yellow solid precipitated between the
aqueous and organic phases, which was separated by filtration. The
pale-yellow solid was washed with ethyl acetate (100 mL) and dried
under vacuum to give a pale-yellow solid (4.67 g), which was identified
as pure product 3a. The combined organic extracts were dried over
MgSO4, filtered and concentrated in vacuo to afford a yellow solid. This
crude product was purified by column chromatography (silica gel/
15:85 ethyl acetate-petroleum ether) to obtain a second fraction of the
title product 3a (1.73 g). Overall, the title compound 3a was obtained
as a yellow solid (6.40 g, 93%). m.p. 168-171 °C. 1H NMR (400 MHz,
DMSO-d6) δ 8.11 (dd, J = 7.6, 1.2 Hz, 1 H), 7.89 (dd, J = 7.6, 1.2 Hz,
1 H), 7.90-7.76 (m, 4 H), 7.78 (td, J = 7.6, 1.2 Hz, 1 H), 7.66 (td,
J = 7.6, 1.2 Hz, 1 H), 5.55 (s, 2 H). 13C NMR (101 MHz, DMSO-d6) δ
162.83, 147.92, 134.69, 133.71, 131.26, 130.04, 129.78, 128.34,
124.67, 123.15, 75.28. HRMS m/z (DART) calculated for MH+
299.0662, found 299.0660.
5.2.5. 1,1,1-Trifluoro-N-(2-nitrobenzyloxy)methanesulfonamide (1a)
A
solution of trifluoromethanesulfonyl chloride (0.683 mL, d
=1.583 g/mL at 25 °C, 6.42 mmol) in anhydrous CH2Cl2 (2.0 mL) was
added dropwise over 3 min at -25 °C to a stirred solution of 4a
(831.2 mg, 4.943 mmol), 4-(N,N-dimethylamino)pyridine (DMAP,
302.1 mg, 2.473 mmol) and anhydrous pyridine (0.40 mL, d =0.978 g/
mL at 25 °C, 4.9 mmol), in anhydrous CH2Cl2 (10 mL) under N2. The
reaction mixture was allowed to warm to room temperature over
30 min. After stirring for 4 h at room temperature, the reaction mixture
was washed with saturated aqueous CuSO4 solution (100 mL), and the
aqueous layer was extracted with CH2Cl2 (3 × 100 mL). The combined
organic extracts were dried over MgSO4, filtered, and concentrated in
vacuo. The resulting crude oil was purified by column chromatography
(silica gel/2:98 MeOH-CH2Cl2) to give the title product 1a as a colorless
oil (599.43 mg, 40%). 1H NMR (400 MHz, CDCl3) δ 8.11 (dd, J = 7.6,
1.2 Hz, 1 H), 7.69 (td, J = 7.6, 1.2 Hz, 1 H), 7.61-7.55 (m, 2 H), 5.46 (s,
2 H). 13C NMR (101 MHz, CDCl3) δ 148.08, 133.82, 130.79, 129.92,
129.69, 125.23, 119.23 (q, J =325 Hz), 77.06. 19F NMR (376 MHz,
CDCl3) δ -73.36. HRMS m/z (DART) calculated for MH+ 301.0101,
found 301.0103.
5.2.2. 2-(4,5-Dimethoxy-2-nitrobenzyloxy)isoindoline-1,3-dione (3b)
A solution of 4,5-dimethoxy-2-nitrobenzyl bromide (2b) (4.500 g,
16.30 mmol) in anhydrous DMF (40 mL) was added dropwise at room
temperature to a stirred solution of N-hydroxyphthalimide (3.000 g,
18.39 mmol) and N,N-diisopropylethylamine (DIEA, 3.40 mL,
d
=0.742 g/mL at 25 °C, 19.5 mmol) in anhydrous DMF (40 mL), under
N2. The reaction mixture was heated to 70 °C (over 30 min) and was
stirred at 70 °C for 7.5 h. The reaction mixture was allowed to cool to
room temperature and was then poured into water (300 mL). The
aqueous layer was extracted with ethyl acetate (3 × 150 mL). A yellow
solid precipitated between the aqueous and organic phases, which was
separated by filtration. This yellow solid was washed with ethyl acetate
(100 mL) and dried under vacuum, to yield pure title compound 3b
(3.56 g) as a yellow solid. The combined organic extracts were dried
over MgSO4, filtered and concentrated in vacuo to afford a yellow solid.
This crude product was purified by column chromatography (silica gel/
30:70 ethyl acetate-petroleum ether) to obtain a second fraction of the
title compound 3b (1.95 g). Overall, the title compound 3b was ob-
tained as a yellow powder (5.51 g, 94%). m.p. 199-200 °C. 1H NMR
(400 MHz, DMSO-d6) δ 7.84 (s, 4 H), 7.68 (s, 1 H), 7.53 (s, 1 H), 5.55 (s,
2 H), 3.89 (s, 3 H), 3.88 (s, 3 H). 13C NMR (101 MHz, DMSO-d6) δ
163.12, 152.74, 148.32, 140.46, 134.81, 128.51, 125.01, 123.28,
112.89, 108.12, 75.54, 56.29, 56.11. HRMS m/z (DART) calculated for
MH+ 359.0874, found 359.0874.
5.2.6. N-(2-Nitrobenzyloxy)methanesulfonamide (1b)
A solution of methanesulfonyl chloride (0.205 mL, d =1.48 g/mL at
25 °C, 2.65 mmol) in anhydrous CH2Cl2 (2.5 mL) was added dropwise at
-20 °C to a stirred solution of 4a (446.56 mg, 2.6557 mmol), DMAP
(326.9 mg, 2.676 mmol) and anhydrous pyridine (0.214 mL,
d
=0.978 g/mL at 25 °C, 2.65 mmol), in anhydrous CH2Cl2 (25 mL) under
N2. The reaction mixture was allowed to warm to room temperature
over 30 min. After stirring for another 1 h at room temperature, the
reaction mixture was washed with saturated aqueous CuSO4 solution
(70 mL), and the aqueous layer was extracted using CH2Cl2
(3 × 50 mL). The combined organic extracts were dried over MgSO4
and concentrated in vacuo. The resulting crude oil was purified by
column chromatography (silica gel/30:70 ethyl acetate-petroleum
ether) to give the title product 1b as a yellow powder (152.40 mg,
23%). In addition, bis-methanesulfonation product 5 was also isolated
as a pale yellow solid (118.86 mg, 14%). Characterization of 1b: m.p.
77-79 °C. 1H NMR (400 MHz, CDCl3) δ 8.06 (dd, J = 7.6, 1.2 Hz, 1 H),
7.67 (td, J = 7.6, 1.2, Hz, 1 H), 7.60 (dd, J = 7.6, 1.2 Hz, 1 H), 7.54 (td,
J = 8.0, 1.6 Hz, 1 H), 7.08 (br s, 1 H), 5.40 (s, 2 H), 3.09 (s, 3 H). 13C
NMR (101 MHz, CDCl3) δ 148.42, 133.50, 131.23, 130.61, 129.64,
125.01, 75.97, 37.12. HRMS m/z (DART) calculated for MH+
247.0383, found 247.0381. Characterization of 5: 1H NMR (400 MHz,
5.2.3. O-(2-Nitrobenzyl)hydroxylamine (4a)
Hydrazine monohydrate (0.567 mL,
d =1.032 g/mL at 25 °C,
11.7 mmol) was added in one portion to a stirred solution of 3a (1.73 g,
5.80 mmol) in anhydrous CH2Cl2 (120 mL) under N2 at room tem-
perature. The reaction mixture was stirred for 4 h at room temperature.
After the resulting white suspension was filtered off, the filtrate was
washed with water (100 mL). The aqueous layer was extracted with
CH2Cl2 (3 × 80 mL) and the combined organic extracts were dried over
MgSO4 and concentrated in vacuo. The title compound 4a was obtained
10