Synthesis and fluorescence of 3,4,6,7,8,9-hexaphenyl-1H-benzo[g]isochromen-1-one

Article abstract of DOI:10.1016/j.jorganchem.2017.12.021

Highly step- and atom-economic synthetic route to 3,4,6,7,8,9-hexaphenyl-1H-benzo[g]isochromen-1-one (1) based on the rhodium catalyzed reaction of terephthalic acid with diphenylacetylene was developed. The best catalytic system for this reaction is [CpRhI₂]_n/Cu(OAc)₂. Compound 1 shows fluorescent properties with a strong Stokes shift.

Full text of DOI:10.1016/j.jorganchem.2017.12.021

Accepted Manuscript
Synthesis and fluorescence of 3,4,6,7,8,9-hexaphenyl-1H-benzo[g]isochromen-1-one
Dmitry A. Loginov, Alexander P. Molotkov, Nikolay E. Shepel
PII:
S0022-328X(17)30706-4
10.1016/j.jorganchem.2017.12.021
JOM 20216
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 16 October 2017
Revised Date: 17 December 2017
Accepted Date: 18 December 2017
Please cite this article as: D.A. Loginov, A.P. Molotkov, N.E. Shepel, Synthesis and fluorescence of
3,4,6,7,8,9-hexaphenyl-1H-benzo[g]isochromen-1-one, Journal of Organometallic Chemistry (2018), doi:
10.1016/j.jorganchem.2017.12.021.
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ACCEPTED MANUSCRIPT
Synthesis and fluorescence of 3,4,6,7,8,9-hexaphenyl-1H-benzo[g]isochromen-1-one
Dmitry A. Loginov,* Alexander P. Molotkov, Nikolay E. Shepel
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 ul.
Vavilova, 119991 Moscow GSP-1, Russian Federation. Fax: +7 499 135 5085; e-mail:
dloginov@ineos.ac.ru
Dedicated to the 85th anniversary of Prof. Irina P. Beletskaya in recognition of her contribution to
the development of the metal-complex catalysis in Russia.
Abstract
Highly step- and atom-economic synthetic route to 3,4,6,7,8,9-hexaphenyl-1H-benzo[g]isochromen-
1-one (1) based on the rhodium catalyzed reaction of terephthalic acid with diphenylacetylene was
developed. The best catalytic system for this reaction is [CpRhI2]n/Cu(OAc)2. Compound 1 shows
fluorescent properties with a strong Stokes shift.
Keywords: C−H activation; Fluorescence; Isocoumarins; Metal complex catalysis; Rhodium
Benzocoumarins and heterocycle-fused coumarin derivatives have found a wide range of
applications in the development of fluorescent probes and tags as well as bioactive materials.1 In
particular, π-extended coumarins are shown to provide stronger fluorescence than parent coumarins
that is expressed by the longer emission wavelength and the higher quantum yield.2 These
advantageous features are caused by extended conjugation.
In contrast to coumarins, synthesis and fluorescent properties of isocoumarins are still poorly
studied. Recently, Makabe with coworkers have developed the synthetic approach to natural
isocoumarin compound, legioliulin, which is a fluorescent substance.3 Legioliulin was synthesized
using cyclic acylpalladation with the following chain elongation by Heck reaction. The 4-
hydroxyidole fused isocoumarins, which are readily available from ninhydrin and enamines of 1,3-
cyclohexanedione, also revealed fluorescent properties with a good quantum yield.4
In the last decade, construction of isocoumarin ring via the catalytic C–H activation of
benzoic acids has gained traction.5 The cobalt,6 ruthenium,7 rhodium8 and iridium9 complexes were

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used as catalysts. Using this approach Ackermann with coworkers synthesized the linear π-extended
isocoumarin (3,4-diethyl-1H-benzo[g]isochromen-1-one) from 2-naphthoic acid and diethylethyne
in 31% yield.10 Similar reaction of 2-naphthoic acid with isopropenyl acetate gave 3-methyl-1H-
benzo[g]isochromen-1-one in 61% yield.11 Herein, we report the direct synthesis of 3,4,6,7,8,9-
hexaphenyl-1H-benzo[g]isochromen-1-one from terephthalic acid and diphenylacethylene as well as
its fluorescent properties.
Selectivity of oxidative coupling of benzoic acids with alkynes catalyzed by
(cyclopentadienyl)rhodium complexes have shown to strongly depend on substituents in the Cp ring.
In particular, the pentamethyl derivative [Cp*RhCl2]2 leads to presumably construction of
isocoumarin moiety,8b whereas the parent unsubstituted complex [CpRhI2]n selectively gives only
naphthalenes (Scheme 1).8c
Ph
COOH
+
H
Ph
[Cp*RhCl2]2,
Cu(OAc)2
[CpRhI2]n,
Cu(OAc)2
O
Ph
Ph
Ph
O
Ph
Ph
Ph
Loginov, 2014
Satoh and Miura, 2007
Scheme 1. Rh-catalyzed coupling of benzoic acid with diphenylacethylene.
We found that both rhodium complexes catalyze reaction of terephthalic acid with
diphenylacetylene giving 3,4,6,7,8,9-hexaphenyl-1H-benzo[g]isochromen-1-one (1) as a result of
formation of the isocoumarin moiety from one carboxylic group and the benzene cycle from another
one (Scheme 2, Table 1). Cu(OAc)2 or Ag2CO3 were used as cocatalysts (necessary for the
regeneration of the initial oxidation state of catalyst). In the case of the [CpRhI2]n/Cu(OAc)2
catalytic system, the intermediate formation of 5,6,7,8-tetraphenyl-2-naphthoic acid was detected by
mass-spectrometry of the reaction mixture (476.4 [M]+), suggesting that the first stage is
construction of the haphthalene moiety. Following annelation of the naphthoic acid formed with the

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next molecule of diphenylacetylene gives the target product 1. The [CpRhI2]n/Cu(OAc)2 system was
found to provide the best result among the tested combinations giving 1 in 31% yield (Entry 1). The
turnover number (TON) is ca. 16. The use of Ag2CO3 as a cocatalyst (Entry 2) or [Cp*RhCl2]2 as a
catalyst (Entries 3 and 4) leads to decrease in yield twice. We considered that low yield of 1 is
connected rather with possible side reactions than inactivation of catalyst. In particular,
hexaphenylbenzene (534.4 [M]+) was also isolated from this reaction as a side product in 24% yield.
To best of our knowledge, the similar reaction with 4-octyne leads to 3,4,8,9-tetrapropylbenzo[1,2-
c:4,5-c′]dipyran-1,6-dione as a result of formation of two isocoumarin moieties from both
carboxylic groups of terephthalic acid.12
Scheme 2. Synthesis of 3,4,6,7,8,9-hexaphenyl-1H-benzo[g]isochromen-1-one (1).
Table 1. Catalyst screening in oxidative coupling of terephthalic acid with diphenylacetylene.a
Entry
Catalyst
Cocatalyst (mmol)
Cu(OAc)2·H2O (1.12)
Ag2CO3 (0.56)
Yield of 1, %
1
2
3
[CpRhI2]n
[CpRhI2]n
[Cp*RhCl2]2
[Cp*RhCl2]2
31
17
15
19
Cu(OAc)2·H2O (1.12)
Ag2CO3 (0.56)
4
a
Reaction conditions: [terephthalic acid]/[diphenylacetylene]/[catalyst] = 0.25:1.0:0.01 (in mmol,
quantity of catalyst is given for monomeric species), in boiling o-xylene under argon.
Solution of 1 in CH3CN demonstrates an intense absorption band with a maximum at 305 nm
(ε305=50354 L×mol-1×cm-1) and also has bands with low intensity at 264 nm (ε264=35569
L×mol-1×cm-1), 350 nm (ε350=16182 L×mol-1×cm-1), 400 nm (ε400=3467 L×mol-1×cm-1) (Figures 1
and 2).

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2.5
2
8.0E+4
6.0E+4
4.0E+4
2.0E+4
0.0E+0
1.5
1
0.5
0
200
250
300
350
400
450
500
200
250
300
350
400
450
Wavelength, nm
Wavelength, nm
Figure 1. The absorption spectrum of 1 in
Figure 2. The extinction spectrum of 1,
CH3CN, C=3·10-5 M, L=1 cm.
[L×mol-1×cm-1], CH3CN.
To obtain fluorescent spectrum, compound 1 was excited at λex corresponding to position
near the maximum of a peak with maximum absorption (λex=305 nm). Emission band in air-
saturated CH3CN solution has its maximum at λem=470 nm (Figure 3) with shoulder at 430 nm.
Fluorescence spectrum's shape and its maximum's position is not excitation wavelength depended
(Figure 4). The shoulder at 400 nm in spectrum (line 1) appears due to the presence of a
microimpurity in the sample. Stokes shifts for emission spectra (lines 1–4) of compound 1 (Figure
4) are 206, 165, 120 and 70 nm for excitation 264, 305, 350 and 400 nm, correspondingly. In
accordance with extended conjugation in structure of 1, those shifts are big enough in comparison to
the Stokes shift of quinine sulphate (108 and 138 nm) in 1N H2SO4 solution (absorption bands 315
and 350 nm, fluorescence band: 453 nm). Noteworthy, the coumarine-6 Stokes shift is only about 50
nm.13
1.00
0.90
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
8.0E+4
7.0E+4
6.0E+4
5.0E+4
4.0E+4
3.0E+4
2.0E+4
1.0E+4
0.0E+0
264 nm
305 nm
350 nm
400 nm
(1)
(2)
(3)
(4)
300
400
500
600
700
320
420
520
620
720
Wavelength, nm
Wavelength, nm

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Figure 3. Fluorescence spectrum of 1 in
CH3CN, C=2·10-6 M, λex.=305 nm, 20°C.
Figure 4. Fluorescence spectra dependence of
1 in CH3CN, C=2·10-6 M; 20°C upon
excitation wavelength. λex.=264 nm – (1), 305
nm – (2) 350 nm – (3), 400 nm – (4).
The quantum yield of compound 1 in air-saturated CH3CN is φem=7.3% upon excitation at
λex.= 305 nm and φem=6.4% for λex= 350 nm. The difference in values can be explained by the error
of the method.
Excitation spectrum (Figure 5) has analogous bands as in absorption spectrum (Figure 1),
suggesting that 1 is individual compound. There are bands with maxima at 311, 350 nm and series
of low intensity band near 400 nm.
8.E+4
7.E+4
6.E+4
5.E+4
4.E+4
3.E+4
2.E+4
1.E+4
0.E+0
220
270
320
370
420
Excitation wavelength, nm
Figure 5. Excitation spectrum of 1, C=2·10-6 M, CH3CN. Emission wavelength λem=465 nm.
In conclusion, we successfully developed a catalytic step-economic protocol for synthesis of
the linear π-extended isocoumarin derivative 1 directly from readily available reactants (terephthalic
acid and diphenylacethylene). Compound 1 reveals strong Stokes shift (by 165 nm) of fluorescence
emission.
Experimental
General: The catalytic reactions were carried out under an inert atmosphere in dry o-xylene.
14
15
1
Catalysts [CpRhI2]n and [Cp*RhCl2]2 were prepared as described in the literature. H and
13C{1H} NMR spectra (δ in ppm) were recorded on a Bruker Avance-400 spectrometer operating at
400.13 and 100.61 MHz, respectively.

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Synthesis of 3,4,6,7,8,9-hexaphenyl-1H-benzo[g]isochromen-1-one (1): A mixture of terephthalic
acid (42 mg, 0.25 mmol), diphenylacetylene (178 mg, 1.0 mmol), [CpRhI2]2 (4.2 mg, 0.01 mmol),
Cu(OAc)2·H2O (223 mg, 1.12 mmol) was refluxed in o-xylene (2 ml) with vigorous stirring for 6 h.
The solvent was removed in vacuo, and the residue was extracted with diethyl ether. The extract was
chromatographed on a silica column (1 × 15 cm). Unreacted diphenylacetylene was washed off with
petroleum ether. Then the first yellow band was collected using mixture of petroleum ether/CH2Cl2
(2:1) as the eluent, giving hexaphenylbenzene (43 mg, 24%) after removal of solvents in vacuo. The
second yellow band was collected using CH2Cl2 as the eluent. After the removal of the solvent in
vacuo, the residue was washed with petroleum ether (3 × 4.5 ml) and dried in vacuo to give 1 as a
1
white solid. Yield 50 mg (31%). EI-MS; m/z: 652.5 [M+]. H NMR (CDCl3) δ: 8.86 (s, 1H), 7.39–
7.40 (m, 3H), 7.20–7.33 (m, 12H), 7.02–7.13 (m, 6H), 6.86–6.91 (m, 10H). 13C{1H} NMR (CDCl3)
δ: 162.24, 149.00, 141.83, 139.95, 139.85, 139.75, 139.69, 138.54, 138.25, 138.13, 135.29, 134.19,
133.61, 132.93, 131.05, 130.99, 130.79, 130.65, 130.68, 130.71, 129.07, 128.61, 128.54, 127.78,
127.66, 127.44, 127.29, 126.99, 126.59, 126.28, 125.59, 125.51, 124.33, 118.50, 116.88. Found (%):
C, 90.28; H, 5.08. Calc. for C49H32O2 (%): C, 90.16; H, 4.94.
Absorption and fluorescence spectroscopy: Spectroscopic grade acetonitrile (HPLC-S, Biosolve,
#01200702) was used for recording of the absorption and fluorescence spectra. Stock solution of
substance 1 with concentration 1×10-3 M was prepared using optically pure acetontrile as a solvent.
Electronic absorption spectrum was measured on a two-channel spectrophotometer Varian-
Cary 300, fluorescence spectra were recorded on spectrofluorimeter FluoroLog-3-221 at 20±1°C in
standard 1 cm quartz cell. The observed fluorescence was detected at a direct angle relative to the
excitation beam. The fluorescence spectra were corrected for the nonuniformity of detector spectral
sensitivity. Fluorescent quantum yield of sample was determined at 20±1°C in solutions of CH3CN
compared to quinine sulphate in 0.5M H2SO4 water solution as a standard (φ=0.55±0.03)16. The
quantum yield was calculated from the equation17:
(1−10−D )× Si ×ni
2
0
ϕifl
= ×
ϕ0fl
(1−10−D )× S0 ×n0
2
i
where ϕifl and ϕ0fl are the quantum yields of the test solution and the standard; Di and D0 are the
absorptions of the test solution and the standard, Si and S0 are areas underneath the fluorescence
spectrum curves for the test solution and the standard, ni and n0 are refraction factors of solvents of
the test compound and the standard compound, respectively.

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Acknowledgements
The work was financially supported by the Russian Science Foundation (Grant No. 17-73-30036).
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Highlights
- The linear π-extended isocoumarin was synthesized from readily available terephthalic acid and
diphenylacethylene.
- Oxidative coupling of benzoic acids with alkynes was extended for terephthalic acid.
- The obtained isocoumarin reveals strong Stokes shift of fluorescence emission.