Please do not adjust margins
RSC Advances
Page 8 of 11
DOI: 10.1039/C6RA19899F
ARTICLE
Journal Name
cooling to room temperature, water was added and solid 7.36 (d, J = 7.5 Hz, 1H), 7.30- 7.33 (m, 4H), 7.14-7.19 (m, 6H), 6.82-
precipitated out was filtered, dried well and collected as crude 6.84 (d, J = 9.0 Hz, 1H), 6.43 (d, J = 2.0 Hz, 1H), 6.23 (dd, J = 9.0 and
product, which was further purified on column chromatography 2.5 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 199.4, 170.1, 164.6, 155.0,
using 3 % MeOH in DCM as the eluent to get the pure product. Yield 145.4, 140.9, 133.7, 132.9, 131.1, 129.6, 129.4, 127.8, 127.4, 126.9,
= 9.7 g (74 %); Melting point = 265-268 oC. 1H NMR (500 MHz, 125.5, 113.1, 110.0, 105.2. Elemental analysis calcd (%); Mol.
DMSO-d6) δ 9.29 (s, 3H), 7.03 (t, J = 8.0 Hz, 3H), 6.36-6.39 (m, 9H). Formula: C26H19NO4 (C: 76.27, H: 4.68, N: 3.42, O: 15.63; Found: C:
13C NMR (126 MHz, DMSO-d6) δ 158.5, 148.8, 130.3, 115.1, 111.5, 76.26, H: 4.64, N: 3.35, O: 15.65).
110.7. Elemental analysis calcd (%); Mol. Formula: C18H15NO3 (C:
73.71, H: 5.15, N: 4.78, O: 16.36; Found: C: 73.72, H: 5.05, N: 4.72,
O: 16.33).
General procedure for the synthesis of RH-1 to RH-5
Initially we planned for the synthesis of RH-2 and RH-5 by treating
DEMAP keto-acid intermediate A with bis-hydroxyl intermediate 3
3-(Diphenylamino)phenol (6)
3-Methoxy-N, N-diphenylaniline
2 (16 g, 58.181 mmol) was
and tris-hydroxyl intermediate 4 respectively, where we isolated
mono and disubstituted RH-1 and RH-4 as by-products with the
main products RH-2 and RH-5 in the reaction mixture. With RH-4
and RH-5, additional polar fluorescent spot was observed on TLC
likely for the mono-substituted rhodamine derivative, attempts to
isolate its pure form were unsuccessful. Similar strategy has been
followed for the synthesis of RH-3, where one more mono-
substituted product was observed on TLC, which we again failed
isolate in its pure form. Di or tri-substituted triphenylamine
hydroxyl derivative (1 eq) and DEMAP or triphenylamine keto acid
(2 eq for RH-1, RH-2 and RH-3 and 3 eq for RH-4 and RH-5) were
dissolved in trifluoroacetic acid (10 ml) and stirred at 95 oC in a
sealed tube for 12 hrs. After completion, the reaction mixture was
poured in ice-water mixture and neutralized by saturated solution
of NaHCO3. The solid precipitated out was filtered, dried and
dissolved in 80 g of pyridine. HCl and heated to 200 oC for 10 hrs.
After cooling to room temperature, water was added and solid
precipitated out was filtered, dried and collected as crude product,
which was further purified on column chromatography using 10%
EtOAc in hexane as the eluent to get the pure product. Yield = 12 g
(79 %); Melting point = 98-100 oC. 1H NMR (500 MHz, CDCl3) δ 7.23-
7.27 (m, 4H), 7.09-7.11 (m, 5H), 7.01-7.07 (m, 2H), 6.64 (dd, J = 8.5
and 2.0 Hz, 1H), 6.52 (t, J = 2.0 Hz, 1H), 6.46 (dd, J = 8.0 and 2.5 Hz,
1H), 4.60 (s, 1H). 13C NMR (126 MHz, CDCl3) δ 156.2, 149.3, 147.6,
130.1, 129.3, 124.7, 123.1, 116.1, 110.4, 109.4. Elemental analysis
calcd (%); Mol. Formula: C18H15NO (C: 82.73, H: 5.79, N: 5.36, O:
6.12; Found: C: 82.72, H: 5.80, N: 5.29, O: 6.10).
purified on column chromatography using 1-5
% MeOH in
2-(4-(Diethylamino)-2-hydroxybenzoyl)benzoic acid (Intermediate
A)
chloroform as eluting system to get the pure products in their
spirocyclic form.
3-(Diethylamino) phenol (10 g, 60.52 mmol) and phthalic anhydride
(9.85 g, 66.57 mmol) were added into anhydrous toluene (100 mL).
The mixture was heated to reflux for 12 hrs and the solid
precipitated out was filtered and purified by column
chromatography (2 % MeOH in chloroform) Yield = 11.6 g (61 %);
Melting point = 202-205 oC.1H NMR (500 MHz, CDCl3) δ 12.47 (s,
1H), 8.10 (d, J = 8.0 Hz, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.54 (t, J = 8.0
Hz, 1H), 7.36 (d, J = 7.5 Hz, 1H), 7.25 (s, 1H), 6.92 (d, J = 9.0 Hz, 1H),
6.27 (s, 1H), 6.19 (s, 1H), 3.38 (q, 4H), 1.19 (t, J = 7.0 Hz, 6H).
Elemental analysis calcd (%); Mol. Formula: C18H19NO4 (C: 68.99, H:
6.11, N: 4.47, O: 20.42; Found: C: 68.97, H: 6.14, N: 4.39, O: 20.43).
3'-(Diethylamino)-6'-((3-hydroxyphenyl)(phenyl)amino)-3H-
spiro[isobenzofuran-1,9'-xanthen]-3-one (RH-1)
Compound 3 (0.3 g, 1.08 mmol) was reacted with Intermediate A
(0.84 g, 2.70 mmol). Yield = 0.2 g (36 %); Melting point = 286 - 291
oC. 1H NMR (500 MHz, CDCl3) δ 11.53 (s, 1H), 8.03 (d, J = 8.0 Hz,
1H), 7.72 (t, J = 7.5 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.58 (dd, J = 9.0
and 2.0 Hz, 1H), 7.40-7.43 (m, 3H), 7.34 – 7.19 (m, 6H), 7.06 (d, J =
2.0 Hz, 1H), 6.84 (d, J = 8.0 Hz, 1H), 6.74 (d, J = 9.0 Hz, 1H), 6.63 (s,
1H), 6.51 (dd, J = 9.0 and 2.0 Hz, 1H), 6.44 (d, J = 2.5 Hz, 1H), 3.36-
3.37 (q, 4H), 1.17 (t, J = 7.0 Hz, 6H). 13C NMR (126 MHz, DMSO-d6) δ
169.1, 152.5, 152.2, 149.6, 148.8, 145.9, 135.9, 130.5, 129.7, 129.6,
126.9, 126.8, 126.0, 125.1, 124.6, 118.7, 113.8, 110.1, 109.1, 104.8,
97.1, 83.8, 44.2, 12.7.
2-(4-(Diphenylamino)-2-hydroxybenzoyl)benzoic
(Intermediate B)
acid
Elemental analysis calcd (%); Mol. Formula: C36H30N2O4 (C: 77.96, H:
5.45, N: 5.05, O: 11.54; Found: C: 77.94, H: 5.36, N: 5.07, O: 11.49).
3-(Diphenylamino) phenol 6 (0.5 g, 1.9 mmol), phthalic anhydride
(0.35 g, 2.3 mmol), anhydrous aluminium chloride (0.38 g, 2.85
mmol) were mixed in ethylene dichloride (15 ml) under nitrogen
atmosphere at 0 oC. The mixture was stirred at 0 oC for 1 hr and
then warmed to room temperature and maintained at room
temperature for 2 hrs. After 2 hrs, reaction mass was stirred at 50
oC for 12 hrs and then it was cooled to room temperature, poured
into 100 ml ice water with continuous stirring. A brownish yellow
sticky precipitate was formed. The product was extracted with
chloroform and the aqueous layer was separated. Organic layer was
washed with water, dried using anhydrous Na2SO4 and then solvent
was removed on rotatory evaporator. The product was purified by
silica gel (100-200 mesh size) column chromatography to obtain
greenish yellow solid as pure product. Yield: 0.4 g (55 %); Melting
Point = 188 – 192 oC. 1H NMR (500 MHz, CDCl3) δ 12.30 (s, 1H), 8.11
(d, J = 8.0 Hz, 1H), 7.63 (t, J = 7.5 Hz, 1 H), 7.54 (t, J = 7.5 Hz, 1H),
3'-(Diethylamino)-6'-(3'-(diethylamino)-3H-spiro[isobenzofuran-
1,9'-xanthen]-3-one(phenyl)amino)-3H-spiro[isobenzofuran-1,9'-
xanthen]-3-one (RH-2)
Compound 3 (0.1 g, 1.08 mmol) was reacted with Intermediate A
(0.84 g, 2.70 mmol).Yield = 0.3 g (39 %); Melting point = 209 - 213
oC. 1H NMR (500 MHz, DMSO-d6) δ 7.97 (d, J = 8.0 Hz, 2H), 7.77 (t, J
= 7.5 Hz, 2H), 7.69 (t, J = 7.5 Hz, 2H), 7.39 (t, J = 7.0 Hz, 2H), 7.29 (d,
J = 8.0 Hz, 2H), 7.16-7.23 (m, 3H), 6.73-6.77 (m, 4H), 6.63 (d, J = 8.5
Hz, 2H), 6.40-6.45 (m, 6H), 3.29 (q, 8H), 1.03 (t, J = 7.0 Hz, 12H). 13
C
NMR δ 169.1, 152.5, 152.2, 149.6, 148.8, 145.9, 135.9, 130.5, 129.4,
129.1, 127.1, 126.8, 126.2, 125.1, 124.5, 118.7, 113.8, 110.1, 109.1,
104.8, 97.3, 83.8, 44.1, 12.7. Elemental analysis calcd (%); Mol.
Formula: C54H45N3O6 (C: 77.96, H: 5.45, N: 5.05, O: 11.54; Found: C:
77.97, H: 5.40, N: 5.07, O: 11.48).
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins