Synthesis and enantiomeric recognition studies of optically active acridone bis(urea) and bis(thiourea) derivatives

Article abstract of DOI:10.1016/j.tetasy.2015.10.004

Novel optically active acridone bis(urea) and bis(thiourea) derivatives were synthesized and their enantiomeric recognition abilities towards the enantiomers of tetrabutylammonium salts of α-hydroxy and N-protected α-amino acids were examined in acetonitrile-DMSO 99:1 using fluorescence spectroscopy.

Full text of DOI:10.1016/j.tetasy.2015.10.004

Tetrahedron: Asymmetry 26 (2015) 1335–1340
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis and enantiomeric recognition studies of optically active
acridone bis(urea) and bis(thiourea) derivatives
Dávid Pál a, Ildikó Móczár a, Attila Kormos a, Péter Baranyai b, László Óvári a, Péter Huszthy a,
⇑
a Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, PO Box 91, H-1521 Budapest, Hungary
b ‘Lendület’ Supramolecular Chemistry Research Group, Institute of Organic Chemistry, Research Centre of Natural Sciences, Hungarian Academy of Sciences, PO Box 286,
H-1519 Budapest, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel optically active acridone bis(urea) and bis(thiourea) derivatives were synthesized and their enan-
Received 24 August 2015
Accepted 9 October 2015
Available online 29 October 2015
tiomeric recognition abilities towards the enantiomers of tetrabutylammonium salts of
a-hydroxy and
N-protected -amino acids were examined in acetonitrile–DMSO 99:1 using fluorescence spectroscopy.
a
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
photostability.36 Acridone37 and certain of its amide, urea,
thiourea38–40 and pyridyloxadiazole41 functionalized achiral
derivatives proved to be efficient receptors for different anions.
Herein we report the synthesis of novel acridone bis(urea) and
bis(thiourea) derivatives (S,S)-1 and (S,S)-2 containing (S)-1-phe-
nylethyl units (Scheme 1), and our studies on their enantiomeric
recognition abilities towards the enantiomers of different optically
active tetrabutylammonium carboxylates in acetonitrile contain-
ing 1% DMSO.
Enantiomeric recognition as
a special case of molecular
recognition, is a frequently occurring and vital phenomenon in
Nature. Examples of its action include the metabolism of single
enantiomeric forms of amino acids and sugars in biosynthetic
pathways. Since each enantiomer of a biologically active chiral
compound may have different physiological properties, the
determination of the enantiomeric composition of chiral organic
compounds has great importance.
The carboxyl group is a very common functional group in amino
acids, enzymes, metabolic intermediates and several biologically
active molecules. Therefore, the synthesis and studies of sensor
and selector molecules, which are able to discriminate between
the enantiomers of chiral carboxylic acids, are of great interest.
The enantiomers of chiral carboxylic acids can not only be
differentiated in their neutral forms, but also as their carboxylates
by enantioselective anion sensors.1–18
Amino acid, BINOL, steroid and monosaccharide units are the
most frequently used chiral building blocks in anion sensors,1–13,18
while 1-arylethyl19–22 moieties have also been applied as sources
of chirality. Urea and thiourea units are often used as the receptor
parts of these sensor molecules because of their high affinity
towards anions due to hydrogen bond formation.9 Some chiral anion
sensors containing two urea or thiourea moieties have a fluorescent
signalling unit, which allows for the examination of the anion
recognition process by sensitive fluorescence spectroscopy.9,22–31
Using an acridone fluorophore unit in a sensor molecule is very
advantageous because of its strong fluorescence32–35 and great
2. Results and discussion
2.1. Synthesis
The synthesis of new acridone bis(urea) and bis(thiourea)
derivatives (S,S)-1 and (S,S)-2 containing (S)-1-phenylethyl units
was carried out as outlined in Scheme 1. Diaminoacridone 3 was
reacted with the appropriate, commercially available optically
active isocyanate (S)-4 and isothiocyanate (S)-5 in DMF to give
acridone derivatives (S,S)-1 and (S,S)-2.
Diaminoacridone 3 was synthesized from dinitroacridone 442–45
by catalytic hydrogenation (yield: 97%, Scheme 2) as a more
efficient and convenient method than the ones published in the
literature (reduction with stannous chloride and hydrochloric acid,
yields: 51–78%42–45 and reduction with sodium hydrosulfite, yield:
63%43).
2.2. Enantiomeric recognition studies
The enantiomeric recognition abilities of receptors (S,S)-1 and
(S,S)-2 towards the enantiomers of tetrabutylammonium salts of
mandelic acid (Man), tert-butoxycarbonyl-protected phenylglycine
⇑
Corresponding author. Tel.: +36 1 463 1071; fax: +36 1 463 3297.
E-mail address: huszthy@mail.bme.hu (P. Huszthy).
http://dx.doi.org/10.1016/j.tetasy.2015.10.004
0957-4166/Ó 2015 Elsevier Ltd. All rights reserved.

1336
D. Pál et al. / Tetrahedron: Asymmetry 26 (2015) 1335–1340
O
N
C
X
O
N
H
(S)-4: X=O
X
NH
NH
HN
X
5
(S)- : X=S
HN
N
H
DMF
H2N
NH2
3
1
(S,S)- : X=O (28%)
(S,S)-2: X=S (27%)
Scheme 1. Synthesis of receptors (S,S)-1 and (S,S)-2.
For the investigation of the complexation properties of recep-
tors (S,S)-1 and (S,S)-2 by fluorescence spectroscopy, excitation
wavelengths (375 nm and 385 nm, respectively) were chosen from
the absorption ranges where the absorbances of the deprotonated
receptors were lower than those of the neutral forms. In this way,
the fluorescence titration spectra upon the addition of the various
chiral carboxylates showed mainly the spectral changes character-
istic of the complexation process, and the deprotonation could be
neglected during the evaluation. The titration series of spectra,
which showed 10–40% emission decreases upon addition of car-
boxylates (Fig. 4), could be fitted satisfactorily by assuming a 1:1
complex formation and the enantioselectivity values were calcu-
lated (Table 2).
Based on these results, receptor (S,S)-1 had an appreciable
enantiomeric recognition ability towards (S)-Boc-Ala over its (R)-
isomer (Fig. 4). However, in the cases of other chiral carboxylates
(Man, Boc-Phg and Boc-Phe) containing a phenyl or benzyl group
at their stereogenic centres, receptor (S,S)-1 showed practically
no enantiomeric discrimination. This can be attributed to an
O
H2 / Pd / C
DMF
3 (97%)
N
H
O2N
NO2
4
Scheme 2. Synthesis of diaminoacridone 3.
(Boc-Phg), tert-butoxycarbonyl-protected phenylalanine (Boc-Phe)
and tert-butoxycarbonyl-protected alanine (Boc-Ala) (Fig. 1) were
studied in acetonitrile containing 1% DMSO by UV–vis and fluores-
cence spectroscopies.
Since basic anions often cause the deprotonation of neutral
anion sensors, we recorded the UV–vis and fluorescence spectra
of the deprotonated forms of receptors (S,S)-1 and (S,S)-2 using
tetrabutylammonium hydroxide as a strong base (Fig. 2).
We also determined the fluorescence quantum yields of the
neutral and deprotonated forms of receptors (S,S)-1 and (S,S)-2
and acridone as a reference compound (Table 1). When comparing
the quantum yields of the neutral forms, a considerably lower
value is observed in the case of thiourea derivative (S,S)-2, which
can be attributed to the quenching effect of the sulfur atoms in
the molecule. It can also be seen that the urea moieties did not sig-
nificantly influence the quantum yield of the acridone core. The
quantum yields of acridone and receptor (S,S)-1 show a slight
decrease, while that of receptor (S,S)-2 shows a significant increase
upon deprotonation. Thus, the quantum yields of the deprotonated
forms are similar.
additional
p–p interaction between the phenyl or benzyl moiety
and one of the urea carbonyl units beside the hydrogen bonded
interactions between the carboxylate and the NH groups. Presum-
ably, the complexes with the enantiomers of Boc-Ala containing an
aliphatic and less bulky methyl group had a different structure
relative to the complexes with Man, Boc-Phg and Boc-Phe, thus
it can render much higher enantiomeric recognition for the former.
It can also be seen that the stability constants of the com-
plexes of receptors (S,S)-1 and (S,S)-2 with Boc-Phe containing
a benzyl group are larger than those with Boc-Phg and Man con-
taining a phenyl group. The change of the urea moieties to
thiourea ones had a significant effect on the enantiomeric recog-
nition, that is, receptor (S,S)-2 showed moderate selectivity
towards the enantiomers of most chiral anions studied (the only
exception was Boc-Phe). The opposite (homochiral) enantioselec-
tivity preference in the case of Boc-Ala can also be explained by
a probably different binding mode to the receptor relative to
Man and Boc-Phg.
Upon the addition of carboxylate anions to receptors (S,S)-1 and
(S,S)-2, the absorption spectral showed changes due to complexa-
tion and in most cases, little to no spectral characteristic changes
to deprotonation were observed (Fig. 3A and B). There was an
exception [(S,S)-1 + Boc-Ala], in which case the absorption spectral
changes due to deprotonation were more significant (Fig. 3C).
H
H
N
H
N
N
COO
COO
COO
Bu4N
HO
COO
Bu4N
Bu4N
Bu4N
Boc
Boc
Boc
*
*
*
*
Boc-Ala
Boc-Phe
Man
Boc-Phg
Figure 1. Optically active tetrabutylammonium carboxylates used in the enantiomeric recognition studies.

D. Pál et al. / Tetrahedron: Asymmetry 26 (2015) 1335–1340
1337
Figure 2. Absorption spectra of (S,S)-1, (S,S)-2 and their deprotonated forms (10 lM) in MeCN–DMSO 99:1, optical path length: 1 cm (A and B); fluorescence emission spectra
of (S,S)-1, (S,S)-2 and their deprotonated forms (10
lM) in MeCN–DMSO 99:1, kex = 366 nm for (S,S)-1 and deprot. (S,S)-1, kex = 364 nm for (S,S)-2 and deprot. (S,S)-2 (C and D).
Table 1
(urea or thiourea) in the anion sensors also influenced the enan-
tiomeric discrimination.
Fluorescence quantum yields of acridone, (S,S)-1, (S,S)-2 and their deprotonated forms
in MeCN–DMSO 99:1
Uf
4. Experimental
4.1. General
Neutral form
Deprotonated form
Acridone
(S,S)-1
(S,S)-2
0.42
0.47
0.071
0.31
0.30
0.25
Starting materials were purchased from Sigma–Aldrich
Corporation unless otherwise noted. Silica gel 60 F254 (Merck)
plates were used for TLC. The ratios of the solvents for the eluents
are given in volumes (mL/mL). Solvents were dried and purified
according to well established methods.46 Evaporations were
carried out under reduced pressure.
Table 2
Stability constants for complexes of (S,S)-1 and (S,S)-2 with the enantiomers of
optically active tetrabutylammonium carboxylates and the degrees of enantiomeric
differentiation in MeCN–DMSO 99:1
Melting points were taken on a Boetius micro-melting point
apparatus and are uncorrected. Optical rotations were taken on a
Perkin–Elmer 241 polarimeter, which was calibrated by measuring
the specific rotations of both enantiomers of menthol. IR spectra
(S,S)-1
(S,S)-2
logK
D
logK
logK
D
logK
(R)-Man
(S)-Man
5.37 0.04
5.38 0.04
5.81 0.09
5.73 0.06
6.38 0.06
6.33 0.05
6.08 0.03
6.64 0.07
ꢀ0.01
0.08
5.52 0.04
5.32 0.05
5.80 0.05
5.54 0.06
6.43 0.11
6.37 0.10
6.18 0.08
6.43 0.07
0.20
were recorded on
a
Bruker Alpha-T FT-IR spectrometer. 1H
(R)-Boc-Phg
(S)-Boc-Phg
(R)-Boc-Phe
(S)-Boc-Phe
(R)-Boc-Ala
(S)-Boc-Ala
0.26
0.06
(500 MHz) NMR spectra were obtained on a Bruker DRX-500
Avance spectrometer. 1H (300 MHz) and 13C (75.5 MHz) NMR spec-
tra were obtained on a Bruker 300 Avance spectrometer. NMR
spectra were taken at 298 K unless otherwise indicated. The signals
of NH protons in the 1H NMR spectra were helped to identify by
shaking the NMR samples with D2O. Mass spectra were recorded
on an Agilent-6120 Single Quadrupole LC/MS instrument using
ESI method. Elemental analyses were performed in the Microana-
lytical Laboratory of the Department of Organic Chemistry,
Institute for Chemistry, L. Eötvös University, Budapest, Hungary.
UV–vis spectra were taken on a Unicam UV4-100 spectropho-
tometer. Quartz cuvettes with path length of 1 cm and 4 cm were
used. Fluorescence spectra were recorded on a Perkin–Elmer LS
50B luminescent spectrometer. Emission spectra were corrected
by the spectrometer software. Quartz cuvettes with path length
of 1 cm were used. Fluorescence quantum yields were determined
relative to quinine sulfate (Uf = 0.53 in 0.1 M H2SO4).31 Stability
0.05
ꢀ0.56
ꢀ0.25
3. Conclusion
Herein we have studied the enantiomeric recognition abilities
of the newly synthesized acridone bis(urea) (S,S)-1 and acridone
bis(thiourea) (S,S)-2 towards the enantiomers of tetrabutylammo-
nium salts of
a-hydroxy and N-protected a-amino acids. The
highest enantioselectivity was observed in the case of receptor
(S,S)-1 and Boc-Ala. The presence of a phenyl or benzyl group in
the carboxylate anion had a significant effect on the enantiomeric
recognition ability of receptor (S,S)-1. The type of the receptor units

1338
D. Pál et al. / Tetrahedron: Asymmetry 26 (2015) 1335–1340
Figure 3. Series of absorption spectra upon titration of (S,S)-2 (5
lM) with (S)-Boc-Phg (0–10 equiv) (A), (S,S)-2 (5 lM) with (S)-Boc-Ala (0–10 equiv) (B) and (S,S)-1 (5 lM)
with (S)-Boc-Ala (0–10 equiv) (C) in MeCN–DMSO 99:1, optical path length: 4 cm.
Figure 4. Series of fluorescence emission spectra upon titration of (S,S)-1 (2 lM) with (R)-Boc-Ala (0–5 equiv) (A) and (S)-Boc-Ala (0–5 equiv) (B) in MeCN–DMSO 99:1,
kex = 375 nm. Titration curves with (R)-Boc-Ala and (S)-Boc-Ala (0–5 equiv) at 440 nm (C).
constants of the complexes were determined by global nonlinear
regression analysis using SPECFIT/32TM software.
The enantiomers of mandelic acid and Boc-protected amino acids
were purchased from Sigma–Aldrich Corporation. The tetrabutyl-
ammonium salts of the anions were prepared by adding 1 equiv of
carboxylic acid to 1 equiv of Bu4NOH dissolved in MeOH. After evap-
orating MeOH, the salts were dried under reduced pressure over
P2O5. During the fluorescence titrations, the concentrations of

D. Pál et al. / Tetrahedron: Asymmetry 26 (2015) 1335–1340
1339
receptors (S,S)-1 and (S,S)-2 were 2
the titrant solutions of chiral carboxylates were 0.5 mM.
l
M and the concentrations of
116.56, 121.59, 121.99, 129.92, 137.46, 177.89; MS calcd for
13H11N3O: 225.1, found (M+H)+: 226.1; Anal. calcd for C13H11
C
N3OꢁH2O: C, 64.19; H, 5.39; N, 17.27. Found: C, 64.47; H, 5.17; N,
4.2.
1,10-(9-Oxo-9,10-dihydroacridine-4,5-diyl)bis{3-[(1S)-1-
17.48.
phenylethyl]urea} (S,S)-1
Acknowledgements
To a solution of diaminoacridone 3 (200 mg, 0.888 mmol) in
DMF (3 mL) was added a solution of isocyanate (S)-4 (274 mg,
1.862 mmol) in DMF (2 mL) under Ar at rt. The mixture was stirred
at rt for 30 min. The precipitate was filtered off, washed with water
and ethanol, and then triturated with butyl acetate. The crude pro-
duct was recrystallized from DMF to yield acridone derivative (S,S)-
1 (129 mg, 28%) as off-white crystals. Mp: >360 °C; Rf: 0.26 (silica
The financial supports of the Hungarian Scientific Research
Fund/National Research, Development and Innovation Office, Hungary
(OTKA/NKFIH Nos. K 112289 and PD 104618), the New Széchenyi
Development Plan (TÁMOP-4.2.1/B-09/1/KMR-2010-0002) and the
Zsuzsanna Szabó Research Fellowship are gratefully acknowledged.
The authors express their appreciation to Dr. György Tibor Balogh
and Dr. Eszter Riethmüller for taking mass spectra, and for
Dr. András Simon for helpful discussion.
gel TLC, MeOH–CH2Cl2 1:20); [
a]
25 = ꢀ28 (c 0.15, DMF); IR (KBr)
D
mmax 3402, 3316, 3262, 3062, 3029, 2980, 2965, 2931, 1635,
1605, 1572, 1524, 1441, 1329, 1264, 1237, 1215, 749, 698,
516 cmꢀ1 1H NMR (500 MHz, DMSO-d6) d 1.43 (d, J = 7 Hz, 6H),
;
4.82–4.99 (m, 2H), 6.90 (d, J = 7 Hz, 2H, NH), 7.15–7.43 (m, 12H),
7.62 (d, J = 7 Hz, 2H), 8.02 (d, J = 8 Hz, 2H), 8.54 (s, 2H, NH), 10.83
(s, 1H, NH); 13C NMR (75.5 MHz, DMSO-d6) d 23.03, 49.10,
120.98, 121.45, 121.67, 125.88, 126.72, 127.47, 128.02, 128.33,
134.93, 144.72, 155.62, 176.92; MS calcd for C31H29N5O3: 519.2,
found (M+H)+: 520.2; Anal. calcd for C31H29N5O3ꢁH2O: C, 69.26;
H, 5.81; N, 13.03. Found: C, 69.51; H, 5.60; N, 13.25.
References
1. Stibor, I.; Zlatušková, P. Top. Curr. Chem. 2005, 255, 31–63.
2. Kubik, S. Chem. Soc. Rev. 2009, 38, 585–605.
3. Brotherhood, P. R.; Davis, A. P. Chem. Soc. Rev. 2010, 39, 3633–3647.
4. Dieng, P. S.; Sirlin, C. Int. J. Mol. Sci. 2010, 11, 3334–3348.
5. Accetta, A.; Corradini, R.; Marchelli, R. Top. Curr. Chem. 2011, 300, 175–216.
6. Zhou, Y.; Yoon, J. Chem. Soc. Rev. 2012, 41, 52–67.
7. Granda, J. M.; Jurczak, J. In SPR—Carbohydrate Chemistry; Rauter, A. P., Lindhorst,
T. K., Queneau, Y., Eds.; RSC: Cambridge, UK, 2014; Vol. 40, pp 445–460.
8. Granda, J. M.; Jurczak, J. Curr. Org. Chem. 2014, 18, 1886–1896.
9. Zhang, X.; Yin, J.; Yoon, J. Chem. Rev. 2014, 114, 4918–4959.
10. Li, Q.; Xu, K.; Song, P.; Dai, Y.; Yang, L.; Pang, X. Dyes Pigm. 2014, 109, 169–174.
11. Xu, K.-X.; Kong, H.-J.; Li, P.; Yang, L.; Zhanga, J.-L.; Wangb, C.-J. New J. Chem.
2014, 38, 1004–1010.
12. Ulatowski, F.; Jurczak, J. Tetrahedron: Asymmetry 2014, 25, 962–968.
13. Ema, T.; Okuda, K.; Watanabe, S.; Yamasaki, T.; Minami, T.; Esipenko, N. A.;
Anzenbacher, P., Jr. Org. Lett. 2014, 16, 1302–1305.
4.3.
1,10-(9-Oxo-9,10-dihydroacridine-4,5-diyl)bis{3-[(1S)-1-
phenylethyl]thiourea} (S,S)-2
To a solution of diaminoacridone 3 (200 mg, 0.888 mmol) in
DMF (3 mL) was added
a solution of isothiocyanate (S)-5
(304 mg, 1.862 mmol) in DMF (2 mL) under Ar at rt. The mixture
was stirred at rt for 10 days. The solvent was removed, and the
residue was triturated with water, ethanol and then butyl acetate.
The crude product was recrystallized from DMF–ethanol to yield
acridone derivative (S,S)-2 (132 mg, 27%) as yellow crystals. Mp:
233–237 °C (decomp.); Rf: 0.39 (silica gel TLC, MeOH–CH2Cl2
14. Xu, K.; Kong, H.; Zu, F.; Yang, L.; Wang, C. Spectrochim. Acta, Part A 2014, 118,
811–815.
15. Botha, F.; Budka, J.; Eigner, V.; Hudecek, O.; Vrzal, L.; Císarová, I.; Lhoták, P.
ˇ
ˇ
Tetrahedron 2014, 70, 477–483.
ˇ
ˇ
16. Macková, M.; Mikšátko, J.; Budka, J.; Eigner, V.; Curínová, P.; Lhoták, P. New J.
Chem. 2015, 39, 1382–1389.
17. Akdeniz, A.; Mosca, L.; Minami, T.; Anzenbacher, P., Jr. Chem. Commun. 2015,
5770–5773.
18. Ulatowski, F.; Jurczak, J. J. Org. Chem. 2015, 80, 4235–4243.
19. Gunnlaugsson, T.; Davis, A. P.; Hussey, G. M.; Tierney, J.; Glynn, M. Org. Biomol.
Chem. 2004, 2, 1856–1863.
1:20); [
a
]
25 = ꢀ21 (c 0.15, DMF); IR (KBr) mmax 3406, 3313, 3261,
D
3062, 3029, 2976, 2936, 1618, 1579, 1531, 1494, 1439, 1371,
1338, 1327, 1288, 1222, 759, 702, 659, 558, 543, 511 cmꢀ1 1H
;
NMR (300 MHz, DMSO-d6) d 1.49 (d, J = 7 Hz, 6H), 5.61 (br s, 2H),
7.17–7.43 (m, 12H), 7.62 (br s, 2H), 8.16 (d, J = 8 Hz, 2H), 8.38 (br
s, 2H, NH), 9.16 (s, 1H, NH), 9.43 (br s, 2H, NH); 1H NMR
(300 MHz, DMSO-d6, 360 K) d 1.54 (d, J = 7 Hz, 6H), 5.56–5.69 (m,
2H), 7.18–7.44 (m, 12H), 7.62 (d, J = 7 Hz, 2H), 8.04 (d, J = 6 Hz,
2H, NH), 8.19 (d, J = 8 Hz, 2H), 9.14 (br s, 3H, NH); 13C NMR
(75.5 MHz, DMSO-d6) d 21.69, 53.42, 121.14, 121.39, 124.41,
126.27, 126.72, 127.39, 128.27, 132.59, 136.71, 143.61, 176.85,
181.96; MS calcd for C31H29N5OS2: 551.2, found (M+H)+: 552.2;
Anal. calcd for C31H29N5OS2ꢁH2O: C, 65.35; H, 5.48; N, 12.29.
Found: C, 65.10; H, 5.19; N, 12.25.
20. Griesbeck, A. G.; Hanft, S.; Miara, Y. D. Photochem. Photobiol. Sci. 2010, 9, 1385–
1390.
21. Trejo-Huizar, K. E.; Ortiz-Rico, R.; Peña-González, M. A.; Hernández-Rodríguez,
M. New J. Chem. 2013, 37, 2610–2613.
22. Zhou, X.-B.; Yip, Y.-W.; Chan, W.-H.; Lee, A. W. M. Beilstein J. Org. Chem. 2011, 7,
75–81.
23. Wei, L.-H.; He, Y.-B.; Xu, K.-X.; Liu, S.-Y.; Meng, L.-Z. Chin. J. Chem. 2005, 23,
757–761.
24. Liu, S.-Y.; He, Y.-B.; Chan, W. H.; Lee, A. W. M. Tetrahedron 2006, 62, 11687–
11696.
25. Costero, A. M.; Colera, M.; Gaviña, P.; Gil, S.; Kubinyi, M.; Pál, K.; Kállay, M.
Tetrahedron 2008, 64, 3217–3224.
26. Kim, Y. K.; Lee, H. N.; Singh, N. J.; Choi, H. J.; Xue, J. Y.; Kim, K. S.; Yoon, J.; Hyun,
M. H. J. Org. Chem. 2008, 73, 301–304.
27. Huang, X.-H.; He, Y.-B.; Chen, Z.-H.; Hu, C.-G.; Qing, G.-Y. Can. J. Chem. 2008, 86,
170–176.
28. Hu, C.; He, Y.; Chen, X.; Huang, Z. Tetrahedron: Asymmetry 2009, 20, 104–110.
29. Costero, A. M.; Llaosa, U.; Gil, S.; Parra, M.; Colera, M. Tetrahedron: Asymmetry
2009, 20, 1468–1471.
30. Wang, F.; Nandhakumar, R.; Hu, Y.; Kim, D.; Kim, K. M.; Yoon, J. J. Org. Chem.
2013, 78, 11571–11576.
31. Lakowicz, J. R. Principles of Fluorescence Spectroscopy, 3rd ed.; Springer Science
+Business Media: New York, NY, 2006.
32. Albert, A. The Acridines, 2nd ed.; Edward Arnold: London, UK, 1966.
33. Acheson, R. M., In The Chemistry of Heterocyclic Compounds, 2nd ed.; Weissberger,
A., Taylor, E. C., Eds.; Wiley: New York, NY, 1973; Vol. 9.
34. Siegmund, M.; Bendig, J. Ber. Bunsen-Ges. Phys. Chem. 1978, 82, 1061–1068.
35. Móczár, I.; Huszthy, P.; Mezei, A.; Kádár, M.; Nyitrai, J.; Tóth, K. Tetrahedron
2010, 66, 350–358.
36. Rothman, J. H.; Still, W. C. Bioorg. Med. Chem. Lett. 1999, 9, 509–512.
37. Miyaji, H.; Sessler, J. L. Angew. Chem., Int. Ed. 2001, 40, 154–157.
38. Blázquez, M. T.; Muniz, F. M.; Sáez, S.; Simón, L. M.; Alonso, Á.; Raposo, C.;
Lithgow, A.; Alcázar, V.; Morán, J. R. Heterocycles 2006, 69, 73–81.
4.4. 4,5-Diaminoacridin-9(10H)-one 3
Dinitroacridone 442–45 (350 mg, 1.227 mmol) was hydrogenated
in DMF (28 mL) at 60 °C in the presence of Pd/C catalyst (35 mg,
10% palladium on charcoal, activated). After the reaction was com-
pleted, the catalyst was filtered off and the solvent was evaporated
to give diaminoacridone 3 (267 mg, 97%) as a green solid which
was used without purification. Mp: >360 °C [lit. mp: 340–
342 °C42 and >320 °C43,44]; Rf: 0.22 (silica gel TLC, AcOH–ace-
tone–toluene 1:2:10); IR (KBr) mmax 3379 (NH2 as), 3307 (NH),
3193 (NH2 s), 3078, 3025, 1656, 1615, 1549, 1528, 1482, 1294,
1239, 827, 743, 589, 548, 495, 435 cmꢀ1 1H NMR (300 MHz,
;
DMSO-d6) d 5.71 (s, 4H, NH), 6.96–7.06 (m, 4H), 7.48–7.57 (m,
2H), 8.74 (s, 1H, NH); 13C NMR (75.5 MHz, DMSO-d6) d 114.20,

1340
D. Pál et al. / Tetrahedron: Asymmetry 26 (2015) 1335–1340
39. García-Garrido, S. E.; Caltagirone, C.; Light, M. E.; Gale, P. A. Chem. Commun.
2007, 1450–1452.
40. Lin, C.; Simov, V.; Drueckhammer, D. G. J. Org. Chem. 2007, 72, 1742–1746.
41. Mashraqui, S. H.; Tripathi, S.; Betkar, R.; Chandiramani, M. Chem. Lett. 2010, 39,
650–651.
43. Klein, E. R.; Lahey, F. N. J. Chem. Soc. 1947, 1418–1419.
44. Dixon, R. P.; Snyder, J. S.; Bradley, L.; Linnenbrink, J. Org. Prep. Proced. Int. 2000,
32, 573–577.
45. Santini, V.; Boyer, G.; Galy, J.-P. Heterocycl. Commun. 2003, 9, 265–270.
46. Riddick, J. A.; Bunger, W. B.; Sakano, T. K., In Techniques of Chemistry, 4th ed.;
Weissberger, A., Ed.; Wiley-Interscience: New York, NY, 1986; Vol. 2.
42. Goldberg, A. A.; Kelly, W. J. Chem. Soc. 1947, 595–597.