Benzophenone-Spiropyran and Naphthalene-Spiropyran Conjugates
1
1
1
08.1, 115.7, 118.7, 120.2, 121.9, 122.8, 123.0, 125.2, 125.4, 125.9,
26.0, 126.4, 127.8, 128.0, 128.6, 128.7, 132.9, 133.6, 136.3, 141.3,
47.4, 159.7.
PhMe/MeCN (2:1, v/v) was heated under reflux and Ar for 14 h.
The mixture was cooled to 0 °C, and the resulting precipitate was
filtered off. The residue was washed with EtOH (5 mL) and hexane
(40 mL) to afford 8 (1.6 g, 52%) as a white solid: FABMS m/z )
1
-[3′,5′-Bis(naphtha-2′′-ylmethoxy)benzyl]-2,3,3-trimethyl-3H-
indolium Bromide (5). A solution of 2,3,3-trimethyl-3H-indole
187 mg, 1.2 mmol) and 4 (472 mg, 1.0 mmol) in PhMe (25 mL)
was heated under reflux and N for 3 d. After the mixture was
+
1
3 3
219 [M + H] ; HNMR [400 MHz, CD CN/CD OD (5:1, v/v)] δ
(
) 2.93 (6H, s), 4.07 (3H, s), 5.32 (3H, s), 9.18 (1H, d, 8 Hz), 9.63
(1H, dd, 1 and 8 Hz), 9.68 (1H, d, 1 Hz); 13C NMR [75 MHz,
2
cooled to ambient temperature, the solvent was distilled off under
reduced pressure. The residue was suspended in hexane (30 mL),
sonicated for 30 min, and filtered to afford 5 (586 mg, 93%) as a
CD
132.2, 133.5, 143.2, 167.5.
,3,3-Trimethyl-2-methylene-5-carboxy-3H-indole (9). A solu-
tion of 8 (1.15 g, 3 mmol) in aqueous KOH (0.32 M, 21 mL) was
stirred at ambient temperature for 2 h. The pH was adjusted to ca.
3 3
CN/CD OD (5:1, v/v)] δ ) 22.4, 36.0, 56.0, 116.4, 125.5,
1
+
1
pink solid: FABMS m/z ) 562 [M - Br] ; H NMR (400 MHz,
CD
3
CN) δ ) 1.34 (6H, s), 2.36 (3H, s), 4.45 (2H, s), 5.21 (4H, s),
.67 (1H, t, 2 Hz), 6.72 (2H, d, 2 Hz), 7.25-7.35 (4H, m), 7.49-
6
7
7
with aqueous HCl (1 M), and the solution was washed with
i-PrOH/CH Cl
(1:1, v/v, 6 × 15 mL). The organic phase was dried
over MgSO , and the solvent was distilled off under reduced
pressure to yield 9 (0.72 g, 99%) as a white solid: FABMS m/z )
.55 (6H, m), 7.84-7.91 (8H, m); 1 C NMR (100 MHz, CD
3
CN)
3
2
2
δ ) 14.3, 22.9, 31.8, 33.8, 70.5, 102.5, 108.5, 125.3, 126.2, 126.5,
4
126.6, 127.9, 128.1, 128.6, 128.8, 132.2, 132.3, 133.3, 133.5, 134.2,
40.0, 160.3.
1
+
1
2
3
2
18 [M + H] ; H NMR (400 MHz, CDCl
3
) δ ) 1.37 (6H, s),
1
-[3′,5′-Bis(naphth-2′′-ylmethoxy)benzyl]-3,3-dimethyl-2-me-
thylene-3H-indole (6). A solution of 5 (146 mg, 0.3 mmol) and
KOH (29 mg, 0.5 mmol) in H O (10 mL) and MeCN (3 mL) was
stirred at ambient temperature for 1 h. The mixture was washed
with CH Cl
(3 × 20 mL), and the organic phase was dried over
MgSO . The solvent was distilled off under reduced pressure to
.11 (3H, s), 4.00-4.02 (2H, m), 6.56 (1H, d, 8 Hz), 7.79 (1H, d,
13
Hz), 7.98 (1H, dd, 2 and 8 Hz); C-NMR (100 MHz, CDCl
3
)
2
δ ) 29.1, 30.0, 43.8, 104.5, 119.1, 123.9, 132.2, 137.9, 151.2, 162.3,
1
71.6.
2
2
1
′,3′,3′-Trimethyl-5′-carboxy-6-nitrospiro[2H-benzopyran-
4
2,2′-3H-indole] (10). A solution of 9 (115 mg, 0.5 mmol) and
afford 6 (90 mg, 62%) as a greenish oil: FABMS m/z ) 562 [M
2-hydroxyl-5-nitrobenzaldehyde (97 mg, 0.6 mmol) in MeCN (25
+
1
+
2
3
H] ; H NMR (300 MHz,CDCl ) δ ) 1.42 (6H, s), 3.92 (2H, d,
mL) was heated under reflux and Ar for 6 h. The mixture was
cooled to 0 °C, and the resulting precipitate was filtered off. The
residue was washed with hexane (50 mL) to yield 10 (121 mg,
Hz), 3.95 (2H, d, 2 Hz), 4.69 (2H, s), 5.20 (4H, s), 6.70 (1H, t,
2
Hz), 6.75 (2H, d, 2 Hz), 7.28-7.40 (4H, m), 7.50-7.60 (6H,
13
m), 7.87-7.92 (8H, m); C NMR (75 MHz, CDCl ) δ ) 23.1,
3
+
1
6
3 2
3%): FABMS m/z ) 367 [M + H] ; H NMR [400 MHz, (CD ) -
3
1
1
3.7, 53.5, 70.2, 102.3, 108.4, 125.3, 125.4, 126.1, 126.2, 126.3,
SO] δ ) 1.13 (3H, s), 1.24 (3H, s), 2.76 (3H, s), 6.02 (1H, d, 10
Hz), 6.70 (1H, d, 8 Hz), 6.92 (1H, d, 9 Hz), 7.26 (1H, d, 10 Hz),
26.4, 126.5, 127.6, 127.7, 127.8, 128.0, 128.5, 133.1, 133.3, 134.1,
39.9, 160.2.
7
9
.69 (1H, d, 8 Hz), 7.81 (1H, dd, 2 and 8 Hz), 8.02 (1H, dd, 3 and
1′-(3′′,5′′-Bis(naphtha-2′′′-ylmethyloxy)benzyl)-3′,3′-dimethyl-
Hz), 8.24 (1H, d, 3 Hz), 12.39 (1H, s); 13C NMR (100 MHz,
6-nitrospiro[2H-1-benzopyran-2′,2′-3H-indole] (SP3). A solution
CDCl
3
) δ ) 19.5, 25.5, 28.4, 51.5, 105.9, 106.2, 115.4, 118.8, 120.9,
21.6, 122.8, 122.9, 125.8, 128.5, 130.8, 135.9, 140.7, 151.2, 158.9,
67.3.
′,3′,3′-Trimethyl-5′-methoxycarbonyl-6-nitrospiro[2H-1-ben-
zopyran-2′,2′-3H-indole] (SP4). A solution of 10 (259 mg, 0.7
mmol), SOCl (114 µL, 2 mmol), and Et N (200 µL, 2 mmol) in
of 6 (97 mg, 0.2 mmol) and 2-hydroxyl-5-nitrobenzaldehyde (43
mg, 0.3 mmol) in PhMe (30 mL) was heated under reflux and N
1
1
2
for 30 h. After being cooled to ambient temperature, the solvent
was distilled off under reduced pressure. The residue was purified
1
by column chromatography [SiO
afford SP3 (65 mg, 53%) as a yellowish solid. HPLC (analytical):
) 4.7 min, PA ) 1.4, APP ) 256.4 ( 0.6 nm; mp ) 60 °C;
2 2 2
: CH Cl /hexanes (1:1, v/v)] to
2
3
MeCN (20 mL) was heated under reflux and Ar for 2 h. MeOH (4
mL) was added, and the solution was allowed to cool to ambient
temperature over 12 h. The solvent was distilled off under reduced
pressure, and the residue was suspended in CH Cl (10 mL) and
2 2
filtered through a Florisil plug. The solvent was distilled off under
t
R
+
1
FABMS m/z ) 712 [M] ; H NMR (500 MHz,CDCl
(
3
) δ ) 1.18
3H, s), 1.30 (3H, s), 4.10 (1H, d, 17 Hz), 4.38 (1H, d, 17 Hz),
5.18 (4H, s), 5.71 (1H, d, 10 Hz), 6.37 (1H, d, 13 Hz), 6.56 (2H,
d, 2 Hz), 6.61 (1H, m), 6.67 (1H, d, 15 Hz), 6.72 (1H, d, 9 Hz),
reduced pressure to give SP4 (231 mg, 85%) as a red solid: HPLC
6
7
.88 (1H, t, 7 Hz), 7.04 (1H, t, 7 Hz), 7.10 (1H, d, 12 Hz), 7.45-
(
analytical) t
) 178 °C; FABMS m/z ) 381 [M + H] ; H NMR (400 MHz,
CDCl ) δ ) 1.24 (3H, s), 1.33 (3H, s), 2.82 (3H, s), 3.89 (3H, s),
.85 (1H, d, 10 Hz), 6.55 (1H, d, 8 Hz), 6.77 (1H, d, 8 Hz), 6.96
1H, d, 10 Hz), 7.76 (1H, d, 2 Hz), 7.97 (1H, dd, 2 and 8 Hz),
R
) 4.7 min, PA ) 1.4, APP ) 256.4 ( 0.6 nm; mp
.52 (6H, m), 7.80-7.87 (8H, m), 7.92 (1H, d, 3 Hz), 8.00 (1H,
+
1
13
dd, 3 and 21 Hz); C NMR (100 MHz, CDCl ) δ ) 20.0, 26.3,
3
3
1
1
1
3.7, 48.0, 52.8, 70.8, 102.6, 106.3, 106.8, 108.1, 108.5, 115.7,
3
5
(
8
2
1
18.7, 120.2, 121.7, 121.8, 122.8, 125.4, 125.5, 126.4, 126.5, 126.6,
27.9, 128.1, 128.4, 128.6, 133.4, 133.5, 134.3, 134.5, 138.9, 147.2,
59.7, 160.6.
.02-8.08 (2H, m); 13C NMR (100 MHz, CDCl
) δ ) 20.1, 26.0,
3
9.0, 51.9, 52.2, 106.4, 115.7, 118.7, 121.1, 121.7, 123.0, 123.5,
26.2, 128.8, 131.5, 136.3, 141.5, 151.8, 159.5, 167.5.
2
,3,3-Trimethyl-5-carboxy-3H-indole (7). A solution of iso-
propylmethylketone (3.9 mL, 36 mmol) and 4-hydrazinobenzoic
acid (5.0 g, 33 mmol) in EtOH (120 mL) and concd H SO (1.0
1′,3′,3′-Trimethyl-5′-(4′′-benzoylbenzoyl)-6-nitrospiro[2H-1-
2
4
mL) was heated under reflux for 12 h. After being cooled to ambient
temperature, the mixture was filtered. A saturated aqueous solution
benzopyran-2′,2′-3H-indole] (SP5). A solution of 10 (77 mg, 0.2
mmol), SOCl (50 µL, 0.6 mmol), and Et N (200 µL, 2 mol) in
MeCN (20 mL) was heated under reflux and Ar for 6 h.
4-Hydroxybenzophenone (55 mg, 0.3 mmol) was added, and the
mixture was allowed to cool to ambient temperature under Ar over
the course of 12 h. The solvent was distilled off under reduced
pressure, and the residue was purified by column chromatography
2
3
of NaHCO
solution was washed with CH
aqueous phase was adjusted to ca. 4 with aqueous HCl (1 M), and
then the solution was washed with CH Cl
3
(50 mL) was added to the filtrate, and the resulting
2
Cl
2
(3 × 20 mL). The pH of the
2
2
(2 × 10 mL). The solvent
of the combined organic phases was distilled off under reduced
pressure to yield 7 (6.7 g, 92%) as a brownish solid: mp ) 192
[SiO
as a red solid: HPLC (analytical) t
276.1 ( 0.6 nm; mp ) 100 °C; FABMS m/z ) 547 [M + H] ; H
NMR (400 MHz, CDCl ) δ ) 1.25 (3H, s), 1.37 (3H, s), 2.87 (3H,
2
, EtCO
2
Me/CH
2
Cl
2
(1:10, v/v)] to afford SP5 (54 mg, 47%)
+
1
°
C; FABMS m/z ) 204 [M + H] ; H NMR (400 MHz, CDCl
3
)
R
) 3.7 min, PA ) 1.2, APP )
+
1
δ ) 1.35 (6H, s), 2.40 (3H, s), 7.69 (1H, d, 8 Hz), 8.07 (1H, d, 1
Hz), 8.15 (1H, dd, 1 and 8 Hz), 10.64 (1H, bs); 13C NMR (100
3
MHz, CDCl
45.5, 156.7, 171.0, 192.9.
,2,3,3-Tetramethyl-5-carboxy-3H-indolium iodide (8). A
solution of 7 (1.80 g, 9 mmol) and MeI (0.55 mL, 2 mmol) in
3
) δ ) 15.6, 23.0, 54.1, 119.7, 123.4, 128.4, 130.9,
s), 5.88 (1H, d, 10 Hz), 6.64 (1H, d, 8 Hz), 6.80 (1H, d, 8 Hz),
7.06 (1H, d, 10 Hz), 7.35 (2H, d, 9 Hz), 7.49-7.52 (2H, m), 7.61
(1H, tt, 1 and 7 Hz), 7.84 (2H, m), 7.92 (3H, m), 8.04-8.07 (2H,
1
1
m), 8.16 (1H, dd, 2 and 8 Hz); 13C NMR (75 MHz, CDCl
) δ )
3
J. Org. Chem, Vol. 72, No. 2, 2007 603