A.K. Vats, et al.
JournalofPhotochemistry&PhotobiologyA:Chemistry394(2020)112467
and finally the crude was purified by flash column chromatography
with 10 % Ethyl acetate: Hexane. The solvent was removed to get the
tilted compound as yellow powder in 77 % yield (3.8 g). FAB-mass
(measured m/z: 502.0 [M+H]+; calculated m/z: 501.3).
acetonitrile was added ethyl iodide flowed by reflux for 12 h. Upon
completion of reaction, solvent was evaporated followed by precipita-
tion using diethyl ether. It was then filtered, washed with diethyl ether
and dried under vacuum to obtain the titled compound 5-(diethox-
yphosphoryl)-1-ethyl-2,3,3-trimethyl-3H-indol-1-ium iodide (iv).
2.3.3. Synthesis of (E)-4-((3-dodecyl-1,1-dimethyl-1H-benzo[e]indol-3-
ium-2-yl)methylene)-2-hydroxy-3-oxocyclobut-1-en-1-olate [4]
2.3.7. Synthesis of SQ-138
3 g (6.0 mmol) of compound [3] was dissolved in 15 mL ethanol in a
50 mL round bottom flask. To this solution 5 equivalent 4 N NaOH was
added and refluxed for 2 h. The reaction mixture was cooled and the
solvent was evaporated under vacuum. After complete evaporation of
the solvent, the reaction mixture was acidified by diluted HCl and
acidified crude was then extracted in chloroform and subjected to
thorough washing by brine. The final hydrolyzed product was obtained
as a red solid in 88 % yield (2.5 g).
To a 50 mL round bottom flask, 1 equivalent of 5-carboxy-1-ethyl-
2,3,3-trimethyl-3H-indol-1-ium iodide (i), (300 mg, 1.3 mmol), 1
equivalent (559 mg, 1.3 mmol) of hydrolyzed semi squaraine dye in-
termediate [4] and 30 mL of 1:1 toluene/n-butanol were added. The
reaction mixture was refluxed for 12 h, which soon turned greenish.
Reaction monitoring was done by TLC, solvent was evaporated under
vacuum after completion and the crude was purified by column chro-
matography using 5% methanol: chloroform solvent. The evaporation
of the collected compound fraction afforded the desired 450 mg of the
compound as a vibrant blue color in 51 % yield. Results of HR-FAB-MS
(measured m/z: 686.4114 [M]+; calculated m/z: 686.4084) and 1H
NMR (500 MHz, CDCl3): δ/ppm = 8.15(dd,H-44); 8.05(dd,H-41);
7.9(dd,H-8); 7.86 (dd,H-9); 7.55(dd,H-45); 7.41(t,H-6); 7.39(t,H-5);
7.27(d, H-7); 6.9(d,H-4); 6.08(s,H-33); 5.9(s,H-28); 4.14 (m,H-46);
3,98(t,H-16); 2.10(t,H-47); 1.82(m,H-17); 1.77(s,H39 + 40); 1.56(s,
H14 + 15); 1.40(m,H-18), 1.39 (m,H-19); 1.38 (m,H-20),1.37(m,H-
21), 1.34(m,H-22);1.33 (m,H-23); 1.31 (m,H-24);1.29 (m,H-25);
1.28(m, H-26), 1.22(t,H-27) confirms the structural identity of this dye.
2.3.4. Synthesis of 1-ethyl-5-hydroxy-2,3,3-trimethyl-3H-indol-1-ium
iodide (ii)
The intermediate 5-hydroxy-2,3,3-trimethyl-3H-indole was synthe-
sized following our previous work [28]. 1 equivalent 4 g (21.1 mmol) of
5-methoxy-2,3,3-trimethyl-3H-indole was dissolved in 20 mL di-
chloromethane. It was then cooled to 0 °C. To the cooled solution, 4 ml
(2 eq.) of Boron tribromide was added dropwise followed by con-
tinuation of reaction at room temperature. The reaction progress was
monitored by TLC and upon completion after 8 h, the reaction was
quenched by sodium thiosulphate followed by solvent extraction using
ethyl acetate and thorough washing with distilled water followed by
brine. The organic layer was evaporated under vacuum and the crude
product was purified by column chromatography using 50 % Ethyl
acetate: Hexane. The desired product was obtained in 72 % yield (2.66
g). The obtained precursor 2.0 g (11.42 mmol) was dissolved in 10 ml
acetonitrile. Then 2 equivalent (1.8 ml, 22.8 mmol) of 1-Iodoethane
was added to it. The reaction mixture was then refluxed for 18 h, while
monitoring the progress by TLC. On completion, solvent was evapo-
rated under vacuum and product was precipitated out adding diethyl
ether. It was then filtered and the titled compound was obtained as
pinkish solid in 63 % yield (2.3 g).
2.3.8. Synthesis of SQ-141
1 equivalent of 1-ethyl-5-hydroxy-2,3,3-trimethyl-3H-indol-1-ium
iodide (ii) 300 mg (0.91 mmol) of and 1 equivalent (392 mg) of semi
squaraine dye intermediate [4] was dissolved in 30 mL of 1:1 toluene/
n-butanol in a round bottom flask fitted with condenser. The reaction
mixture was refluxed for 18 h. After complete removal of the solvent,
the crude was subjected to flash column chromatography with chloro-
form methanol as the eluting agent to afford a vibrant blue solid (285
mg) in 43 % yield. HR-FAB-MS (measured m/z: 658.4131 [M]+; cal-
culated m/z: 658.4134). 1H NMR (500 MHz, CDCl3): δ/ppm
=
9.74.15(dd,H-43); 8.12(dd,H-41); 7.82(dd,H-8); 7.79 (dd,H-9);
7.51(dd,H-44); 7.49(t,H-6); 7.48(t,H-5); 7.20(d, H-7); 6.8(d,H-4);
5.9(s,H-33); 5.89(s,H-28); 4.02(m,H-45); 3.58(t,H-16); 2.10(t,H-46);
1.98(m,H-17); 1.78(s,H39 + 40); 1.50(s, H14 + 15); 1.41(m,H-18),
1.40(m,H-19); 1.38(m,H-20); 1.37(m,H-21), 1.34(m,H-22); 1.32(m,H-
23); 1.31(m,H-24); 1.29(m,H-25); 1.28(m, H-26), 1.21(t,H-287).
2.3.5. Synthesis of 5-sulfo-1-ethyl-2,3,3-trimethyl- -3H-indol-1-ium iodide
(iii)
The intermediate was synthesized following the report by Park et al.
[29]. 5-Sulfo-2,3,3-trimethyl-3H-indole was synthesized by the reaction
of 4-Hydrazino-benzenesulfonic acid hemihydrate 4 g (21.3 mmol) with
5 mL of 3-methyl-2-butanone in 20 mL acetonitrile under reflux for 7 h.
Reaction monitoring was done by TLC and upon completion of reaction,
solvent was evaporated and the crude was purified by column chro-
matography to give the product in 75 % yield. 2.5 g (10.4 mmol) of this
compound was dissolved in 15 ml of acetonitrile and 2 equivalents of 1-
Iodoethane (4 ml, 20.8 mmol) was added. The mixture was then re-
fluxed for 12 h while monitoring the reaction progress by TLC. The
solvent was evaporated under vacuum and ample diethyl ether was
added for precipitation, which was filtered to get the titled compound
as pinkish solid in 68 % yield (2.8 g).
2.3.9. Synthesis of SQ-142
To a round bottom flask fitted with condenser, 400 mg (1.5 mmol)
of 5-sulfo-1-ethyl-2,3,3-trimethyl-3H-indol-1-ium iodide and 1 equiva-
lent (646 mg) of semi squaraine dye intermediate [4] was dissolved in
30 mL of 1:1 toluene/n-butanol. The reaction mixture was then refluxed
for 18 h. Thereafter the solvent was evaporated and the crude was
purified with column chromatography using chloroform methanol sol-
vent system. 400 mg of the desired compound was collected as a blue
solid in 40 % yield. HR-FAB-MS (measured m/z: 722.3759 [M]+; cal-
culated m/z: 722.3753). 1H NMR (500 MHz, CDCl3): δ/ppm
=
9.73(dd,H-44); 8.12(dd,H-41); 7.81(dd,H-8); 7.79(dd,H-9); 7.50(dd,H-
45); 7.39(t,H-6); 7.35(t,H-5); 7.19(d,H-7); 6.9(d,H-4); 4.04(s,H-33);
4.02(s,H-28); 3.67(m,H-46); 3.63(t,H-16); 2.14(t,H-47); 2.06(m,H-17);
1.84(s,H39 + 40); 1.56(s, H14 + 15); 1.44(m,H-18), 1.42(m,H-19);
1.39(m,H-20); 1.36(m,H-21), 1.34(m,H-22); 1.33(m,H-23); 1.31(m,H-
24); 1.29(m,H-25); 1.28(m,H-26), 1.27(t,H-27).
2.3.6. Synthesis of 5-(diethoxyphosphoryl)-1-ethyl-2,3,3-trimethyl-3H-
indol-1-ium iodide (iv)
The compound was synthesized by slightly modified procedure as
reported by Archer et al. [30]. To a solution of 4-Iodoindole (1 g, 3.5
mmol) in toluene was added Tetrakis (triphenylphosphine) palladium
(0) (0.18 mmol), and triethylamine (12.4 mmol) followed by addition
of Diethylphosphite (0.31 mmol) and reaction mixture was refluxed for
12 h. Upon completion of reaction as monitored by TLC, solvent was
evaporated. Product was extracted with ethyl acetate and washed with
water and brine. Finally, it was purified by column chromatography
giving desired compound diethyl (2,3,3-trimethyl-3H-indol-5-yl) phos-
2.3.10. Synthesis of SQ-143
315 mg of 5-(diethoxyphosphoryl)-1-ethyl-2,3,3-trimethyl-3H-
indol-1-ium iodide (iv) and 302 mg of semi squaraine dye intermediate
[4] was dissolved in 1:1 toluene/n-butanol in a round bottom flask. The
reaction mixture was then refluxed for 18 h. The solvent was evapo-
rated and the crude was subjected to flash column chromatography
phonate as colorless liquid. To
a solution of this compound in
4