Coumarin-Appended Stable Fluorescent Self-Complementary Quadruple-Hydrogen-Bonded Molecular Duplexes

Article abstract of DOI:10.1021/acs.joc.7b01249

In this paper we report a coumarin-conjugated self-assembling system adorned with valuable features such as high duplex stability and a built-in fluorophore, which would augment its application potential. This system forms a highly stable molecular duplex

Full text of DOI:10.1021/acs.joc.7b01249

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Article
Coumarin-appended Stable Fluorescent Self-complementary
Quadruple Hydrogen-bonded Molecular Duplexes
Sanjeev Kheria, Suresh Rayavarapu, Amol Kotmale, Dinesh R.
Shinde, Rajesh G. Gonnade, and Gangadhar Jessy Sanjayan
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 30 May 2017
Downloaded from http://pubs.acs.org on June 1, 2017
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Coumarin-appended Stable Fluorescent Self-complementary Quadruple Hydrogen-
bonded Molecular Duplexes
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Sanjeev Kheria,† Suresh Rayavarapu,† Amol S. Kotmale,§ Dinesh R. Shinde,§
Rajesh G. Gonnade,‡ and Gangadhar J. Sanjayan*,†
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†Organic Chemistry Division, §Central NMR Facility, ‡Centre for Materials Characterization,
CSIRꢀNational Chemical Laboratory (CSIRꢀNCL), Dr. Homi Bhabha Road, Pune 411008,
India. Eꢀmail: gj.sanjayan@ncl.res.in
ABSTRACT
This article reports coumarinꢀconjugated selfꢀassembling system adorned with
valuable features such as high duplex stability and a builtꢀin fluorophore, which would
augment its application potential. This system forms highly stable molecular duplex in nonꢀ
polar solvent (Kdim > 1.9 x 107 Mꢀ1 in CDCl3). Due to the fluorescent property of coumarin,
these new structural motif may find potential application in material chemistry and
supramolecular chemistry.
INTRODUCTION
Supramolecular chemistry1 has attracted considerable interest in recent years, owing
to its wide application potential in chemical biology, nanotechnology, and material science.2
A realꢀlife example of hydrogen bonding is the double helix structure of DNA, where two
complementary strands are intertwined by means of hydrogen bonds and πꢀπ stacking in a
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selfꢀassembly process. Inspired by Nature’s use of DNA base pairs like purines and
pyrimidines, organic chemists have designed synthetic hydrogen bonding motif that can selfꢀ
assemble to form supramolecular architectures.3 Among the various hydrogen bonded
duplexes, quadruple hydrogen bonded dimers have been widely explored, studied and
attained significant importance due to their simplicity in design and synthetic accessibility.4a
Due to its high dimerization constant (Kdim > 107 Mꢀ1) and facile synthetic accessibility,
Meijer’s ureidopyrimidone4 (UPy) system has emerged as a promising building block having
widespread applications in diverse areas such as material chemistry, catalysis and
supramolecular polymers (Figure 1a).5 High duplex stability is also exhibited by deazapterinꢀ
based selfꢀassembling system, which is somewhat closely related to Meijer’s system (Figure
1b).6 It is noteworthy that selfꢀassembly of heterocycleꢀbased UPy systems are often
associated with tautomerization, and as a result, the protamers (keto and enol forms) generate
different structures, both in the solutionꢀ and in the solidꢀstate.4a
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Figure 1. AADDꢀtype selfꢀassembling systems forming highly stable duplexes.
The modified coumarinꢀappended UPy system reported herein actually exists as
dimers of pyrimidinone and pyrimidinol tautomeric forms, stabilized by linear array of four
hydrogen bonds (Figure 2). The dimers are arranged via AADD as well as DADA arrays of
selfꢀcomplementary type hydrogen bonding. In addition, there is also preꢀorganisation via
S(6)ꢀtype intramolecular hydrogen bond in both the dimers to further enhance their stability
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significantly. To the best of our knowledge, this is the first report of an UPy wherein
coumarin moiety is fused on the backbone. As coumarin moiety itself is fluorescent, the
resulting selfꢀassembling systems 1 exhibit strong fluorescent properties.
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Figure 2. Equilibria between tautomeric forms and between monomer and dimer of selfꢀ
assembling system 1 reported herein.
RESULTS AND DISCUSSION
Coumarinꢀappended fluorescent selfꢀassembling motif 1 could be synthesised in a
straightforward synthetic route as depicted in scheme 1. Diethyl 1,3ꢀacetonedicarboxylate on
reacting with guanidine carbonate gave ethyl isocytosineꢀ6ꢀacetate 4,7 which on condensation
with 4ꢀ(dialkylamino) salicylaldehyde 5a,b furnished the amine 6a,b. Finally, the amine 6a,b
on reacting with different isocyanates under heating condition in pyridine resulted in the
formation of selfꢀassembling systems 1a-e in good yields (Scheme 1).
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Scheme 1. Synthesis of compounds 1a
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aReagents and conditions: (i) EtOH, reflux, 24 h; (ii) piperidine (cat), EtOH, reflux, 10 h; (iii)
R2NCO, pyridine, 100 °C, 10 h.
The duplex formation by 1a and 1d were investigated, as representative examples, by
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1H NMR experiments. In their H NMR spectrum in CDCl3, 1a and 1d showed two sets of
signals. One set of major NꢀH signals at 14.24, 11.79, 9.95 ppm and 14.23, 11.90, 10.73 ppm
were assigned to the pyrimidinone tautomers of 1a and 1d, respectively. A second set of
minor signals at 13.54, 11.22, 9.81 ppm and 13.39, 11.41, 10.36 ppm were assigned to the
pyrimidinol tautomers of 1a and 1d, respectively, with a relative abundance of ~ 20%. The
relative amounts of the pyrimidinone and pyrimidinol tautomers were determined based on
the relative integrating intensity of the benzylic proton signal of 1d. The significant
downfield shift of NHs of 1a and 1d were indicative of strong intermolecular hydrogen
bonding interactions involving the urea NH protons. Furthermore, the far downfield shift of
NH signals of 1a and 1d at 14.24 and 14.23 ppm, respectively, clearly suggested the strong
involvement of intramolecular bifurcated Hꢀbonding.
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The dimerization of 1d was investigated by 1H NMR dilution experiments
(Supporting Information, Figure S16). When a CDCl3 solution of 1d was diluted from 100
mM to 10 µM, no detectable changes were observed in the chemical shift values of all the
NH protons. This showed that dimerization of 1d persisted at a lower concentration in CDCl3
with high Kdim value. Conservatively assuming more than 95% dimer formation at the lowest
concentration studied (10 µM), the Kdim of compound 1d was estimated to be at a lower limit
of 1.9 x 107 Mꢀ1 in CDCl3.
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The dimerization of 1d in various DMSOꢀd6/CDCl3 mixtures was studied in order to
further support selfꢀassembly by increasing the polarity of the solvent. The Kdim values of
1d·1d was determined quantitatively in the range from 5% to 20% DMSOꢀd6/CDCl3 (v/v)
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mixtures by H NMR dilution experiments. In 5% and 10% DMSOꢀd6/CDCl3 mixtures, we
observed negligible chemical shift changes of urea protons. Therefore, Kdim values were
estimated to be at a lower limit of 105 Mꢀ1 for 1d under this condition. These findings proved
that the duplexes are quite stable in mixture of solvents even though DMSO is a strongly
competitive solvent for hydrogen bonded complexes. Nonlinear regression analysis8 of the
chemical shift gave the dimerization constant Kdim value of 7.4 Mꢀ1 for 1d in 20% DMSOꢀ
d6/CDCl3 mixture.
1
The stability of molecular duplexes was further studied by variable temperature H
NMR studies (ranging from 223ꢀ323 K). Signals of NH2 (ꢀ0.60 ppb Kꢀ1 for 1a and ꢀ0.23 ppb
Kꢀ1 for 1d) and NH3 (ꢀ2.40 ppb Kꢀ1 for 1a and ꢀ2.35 ppb Kꢀ1 for 1d) showed temperature
coefficients suggestive of their strong involvement in intermolecular hydrogen bonds when
compared to NH1 which is involved in intramolecular S(6)ꢀtype hydrogen bonds (ꢀ3.20 ppb
Kꢀ1 for 1a and ꢀ2.94 ppb Kꢀ1 for 1d). These values also indicate the high stability of the
molecular duplexes (Supporting Information, Figure S1 and S3).
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The selfꢀassembling systems 1 exhibited fluorescence due to the presence of the
coumarin moiety on the backbone of the UPy selfꢀassembling systems. Therefore, the duplex
stability of 1d·1d was also investigated, as a representative example, by fluorescence
spectroscopic methods, in addition to NMR methods (vide supra). By using a fluorescence
spectroscopic method, as reported previously by the Meijer group,4b the dimerization constant
of 1d was determined. Concentrationꢀdependent changes in the intensities of 1d at 497 nm
appeared in the range of 10ꢀ10 M to 10ꢀ7 M in chloroform. Nonlinear regression analysis8a of
the fluorescence data gave a dimerization constant Kdim value of (2.18 ± 1.81) x 108 Mꢀ1 for
1d (Supporting Information, Figure S20 and S21).
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The duplex formation was further investigated via solutionꢀstate NMR and HRMSꢀ
ESI studies. Twoꢀdimensional 15N HSQC NMR studies in CDCl3 confirmed that 1a and 1d
exist in two tautomeric forms, A and B in solution. The major tautomer is pyrimidinone
tautomer, A with AADDꢀtype selfꢀcomplementary Hꢀbonding arrays whereas the minor
tautomer is pyrimidinol tautomer, B having DADAꢀtype selfꢀcomplementary Hꢀbonding
arrays in solution (Figure 3). In addition, HRMSꢀESI mass spectra showed molecular ion
peaks (963.5451 for [1a·1a + H]+, calcd 963.5444) and (1255.7642 for [1d·1d + H]+, calcd
1255.7640), corresponding to the presence of the duplex (Supporting Information, page S6
and S18).
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(a)
(b)
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NH1 of A
NH2 of A
NH of B
NH3 of A
NH1 of A
OH of B
NH2 of A
NH of B
NH3 of A
NH of B
OH of B
NH of B
ppm
ppm
NH2 of A
NH3 of A
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120
NH2 of A
100
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NH1 of A
NH1 of A
NH of B
NH of B
NH3 of A NH of B
NH of B
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13.0
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11.0
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ppm
Figure 3. 2D 15N HSQC spectra of 1a (a) and 1d (b) (CDCl3, 500 MHz, 298 K).
After several trials of crystallization in a variety of solvents, slow evaporation from
CH2Cl2 solvent resulted in the formation of crystals of 1a as pyrimidinol dimers (Figure 4).9
Xꢀray crystallography studies unambiguously revealed the formation of hydrogen bonded
molecular duplex. From the Xꢀray structure, it is amply clear that the CꢀC bond connecting
UPy and the coumarin ring is rotated, as a result, the homodimer is arranged in DADA
sequence. The duplex is held together by four C(4)ꢀtype intermolecular hydrogen bonds
between the selfꢀcomplementary DADAꢀtype linear hydrogenꢀbonding arrays, which is
further stabilized by an intramolecular NꢀH•••N hydrogen bond (bond distance is 2.006 Å).
The outer OꢀH•••O hydrogen bonds are slightly shorter than the inner NꢀH•••N bonds, as
seen in Meijer’s ureidopyrimidone.4a The hydrogen bond distances of OꢀH•••O is 1.747 Å
and NꢀH•••N is 2.141 Å. The bond angles of OꢀH•••O is 162° and NꢀH•••N is 168°. Thus,
there is 0.394 Å difference between the outer OꢀH•••O and the inner NꢀH•••N bonds.
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Figure. 4. Singleꢀcrystal Xꢀray structure of dimer 1a.9 Hydrogen bonding is highlighted in
dashes (salmon colored), above which hydrogen bond distances (OꢀH•••O and NꢀH•••N) are
displayed in Å. All hydrogens, other than those at the hydrogenꢀbonding sites, have been
removed for clarity.
CONCLUSION
In summary, based on the results obtained from extensive NMR studies, we could
unambiguously confirm that the modified coumarinꢀappended ureidopyrimidoneꢀbased selfꢀ
complementary quadruple hydrogenꢀbonded systems show high Kdim value (Kdim > 107 Mꢀ1 in
CDCl3). Advantageously, using this strategy, we could also design a novel quadruple
hydrogen bonding system tethered with a fluorophore, which could augment its application
potential in supramolecular chemistry. We believe that this new structural motif having high
stability may have potential applications in the field of supramolecular chemistry as well as in
making OPV devices.
EXPERIMENTAL SECTION
General methods
Unless otherwise stated, all the chemicals and reagents were obtained commercially.
Compound 4 was synthesized as per the reported procedure.7 Dry solvents were prepared by
the standard procedures. Analytical Thin Layer Chromatography was done on precoated
silica gel plates (Kieselgel 60F254, Merck). Column chromatographic purifications were done
with 100ꢀ200 mesh silica gel. NMR spectra were recorded in CDCl3 on AV 200 MHz, AV
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400 MHz, AV 500 MHz and AV 700 MHz Bruker NMR spectrometers. All chemical shifts
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are reported in
δ ppm downfield to TMS and peak multiplicities are referred to as singlet (s),
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doublet (d), quartet (q), broad singlet (bs), and multiplet (m). The titration studies were done
in CDCl3. Elemental analyses were performed on an ElmentarꢀVarioꢀEL (Heraeus Company
Ltd., Germany). IR spectra were recorded in CHCl3 using Shimadzu FTIRꢀ8400
spectrophotometer. Melting points were determined on a Buchi Melting Point Bꢀ540. HRMS
measurements were carried out using ESI method and ionꢀtrap mass analyzer.
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2-Amino-6-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)pyrimidin-4(1H)-one (6a)
To a solution containing 4ꢀ(diethylamino) salicylaldehyde (5a) (0.980 g, 5.076 mmol, 1
equiv.), compound 4 (1 g, 5.076 mmol, 1 equiv.), in 20 ml of absolute EtOH, piperidine
(catalytic) amount was added and the reaction mixture was refluxed for 10 h. The reaction
mixture was cooled to room temperature, and the resulting precipitate was filtered, washed
thoroughly with chilled EtOH and dried under vacuum gave the desired compound 6a (1.3 g,
o
77%) as a yellow solid. mp: > 295 C; IR (CHCl3) ν (cmꢀ1): 3344, 3154, 2977, 1709, 1671,
1583, 1462, 1261, 1134, 776; 1H NMR (200 MHz, DMSOꢀd6) δ: 10.75 (bs, 1H), 8.69 (s, 1H),
7.53ꢀ7.49 (d, J = 8.97 Hz, 1H), 6.75ꢀ6.74 (m, 1H), 6.69 (s, 1H), 6.55 (s, 1H), 6.48 (bs, 2H),
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3.50ꢀ3.43 (m, 4H), 1.16ꢀ1.09 (t, J = 6.82 Hz, 6H); C NMR (50 MHz, DMSOꢀd6) δ: 163.4,
159.5, 157.2, 156.5, 154.6, 151.6, 143.7, 130.7, 114.0, 109.6, 107.7, 100.4, 95.8, 44.2, 12.3;
HRMS (ESI) calculated [M+H]+ for C17H19O3N4: 327.1447, found 327.1452.
1-(6-(7-(Diethylamino)-2-oxo-2H-chromen-3-yl)-4-oxo-1,4-dihydropyrimidin-2-yl)-3-(2-
ethylhexyl)urea (1a)
To a solution of 6a (0.2 g, 0.613 mmol, 1 equiv.) in dry pyridine (5 ml), 2ꢀethylhexyl
isocyanate (0.214 ml, 1.226 mmol, 2 equiv.) was added and the reaction mixture was allowed
o
to stir at 100 C for 10 h. The resulting suspension was evaporated to dryness and column
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chromatographic purification (eluent: 10% MeOH/ DCM, Rf: 0.4) of the residue yielded 1a
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(0.191 g, 65%) as a yellow solid. mp: 244ꢀ246 C; IR (CHCl3) ν (cmꢀ1): 3747, 3208, 3082,
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2921, 1722, 1664, 1593, 1450, 1389, 1258, 1151, 788; 1H NMR (400 MHz, CDCl3) δ: 14.24
(s, 1H) (major protomer, 80%), 13.54 (s, 1H) (minor protomer, 20%), 11.79 (s, 1H) (major
protomer, 80%), 11.22 (s, 1H) (minor protomer, 20%), 9.95 (s, 1H) (major protomer, 80%),
9.81 (s, 1H) (minor protomer, 20%), 8.29 (s, 1H) (minor protomer, 20%), 8.00 (s, 1H) (major
protomer, 80%), 7.38ꢀ7.36 (d, J = 9.05 Hz, 1H), 6.66ꢀ6.63 (dd, J = 9.05 Hz, J = 2.20 Hz, 1H),
6.49 (m, 1H), 6.43 (s, 1H), 3.49ꢀ3.44 (q, J = 7.09 Hz, 4H), 3.31ꢀ3.20 (m, 2H), 1.48ꢀ1.36 (m,
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1H), 1.32 (m, 6H), 1.27ꢀ1.23 (m, 8H), 0.93ꢀ0.81 (m, 6H); C NMR (100 MHz, CDCl3) δ:
172.8, 159.9, 157.1, 156.1, 154.3, 152.6, 145.5, 143.1, 142.6, 130.6, 130.1, 109.9, 109.4,
108.2, 108.0, 103.0, 96.7, 45.1, 45.0, 43.4, 39.5, 38.9, 31.0, 30.7, 28.8, 28.7, 24.2, 23.9, 23.1,
22.9, 14.1, 14.0, 12.4, 10.8, 10.6; HRMS (ESI) calculated [M+H]+ for C26H36O4N5: 482.2757,
found 482.2762, 963.5451 [2M+H]+.
1-Benzyl-3-(6-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-4-oxo-1,4-dihydropyrimidin-2-
yl)urea (1b)
Following the same procedure for synthesis of compound 1a and using benzyl isocyanate, 1b
was synthesized. Purification was effected by column chromatography (eluent: 10% MeOH/
DCM, Rf: 0.5) to yield 1b (0.2 g, 71%) as a yellow fluffy solid. mp: 268ꢀ270 oC; IR (CHCl3)
ν (cmꢀ1): 3206, 3130, 2974, 1722, 1666, 1582, 1453, 1259, 854; 1H NMR (400 MHz, DMSOꢀ
d6) δ: 11.60 (s, 1H), 9.88 (s, 1H), 8.52 (s, 1H), 7.76 (s, 1H), 7.38ꢀ7.34 (m, 5H), 7.28ꢀ 7.25 (m,
1H), 6.97 (s, 1H), 6.73ꢀ6.70 (dd, J = 8.8 Hz, J = 1.22 Hz, 1H), 6.52 (s, 1H), 4.41ꢀ4.39 (d, J =
5.62 Hz, 2H), 3.45 (m, 4H), 1.14ꢀ1.11 (t, J = 6.85 Hz, 6H); 13C NMR (100 MHz, DMSOꢀd6)
δ: 159.4, 156.6, 154.8, 151.9, 144.0, 138.9, 130.9, 128.5, 127.2, 127.1, 112.8, 109.8, 107.7,
95.8, 44.3, 42.8, 12.3; HRMS (ESI) calculated [M+H]+ for C25H26O4N5: 460.1974, found
460.1979, 919.3886 [2M+H]+.
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1-(6-(7-(Diethylamino)-2-oxo-2H-chromen-3-yl)-4-oxo-1,4-dihydropyrimidin-2-yl)-3-
dodecylurea (1c)
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Following the same procedure for synthesis of compound 1a and using dodecyl isocyanate,
1c was synthesized. Purification was effected by column chromatography (eluent: 10%
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MeOH/ DCM, Rf: 0.5) to yield 1c (0.181 g, 55%) as a yellow solid. mp: 240ꢀ242 C; IR
(CHCl3) ν (cmꢀ1): 3747, 3284, 3118, 2919, 2849, 1711, 1647, 1565, 1415, 1194, 775; H
1
NMR (400 MHz, CDCl3) δ: 14.30 (s, 1H) (major protomer, 80%), 13.50 (s, 1H) (minor
protomer, 20%), 11.72 (s, 1H) (major protomer, 80%), 11.29 (s, 1H) (minor protomer, 20%),
10.08 (s, 1H) (major protomer, 80%), 9.92 (s, 1H) (minor protomer, 20%), 8.31 (s, 1H)
(minor protomer, 20%), 8.01 (s, 1H) (major protomer, 80%), 7.38ꢀ7.37 (m, 1H), 6.66ꢀ6.64
(m, 1H), 6.50 (s, 1H), 6.43 (s, 1H), 3.55ꢀ3.40 (m, 4H), 3.38ꢀ3.24 (m, 2H), 1.80ꢀ 1.64 (m, 2H),
1.25ꢀ1.10 (m, 24H), 0.87 (m, 3H); 13C NMR (100 MHz, CDCl3) δ: 173.0, 159.9, 157.2,
156.0, 154.3, 152.6, 145.6, 142.6, 130.6, 109.9, 108.3, 108.1, 102.9, 96.8, 45.1, 45.0, 40.1,
31.9, 29.6, 29.3, 27.0, 22.6, 14.1, 12.4; HRMS (ESI) calculated [M+H]+ for C30H44O4N5:
538.3386, found 538.3388, 1075.6703 [2M+H]+.
3-(Bis(2-ethylhexyl)amino)phenol (9)10
To a solution of 3ꢀaminophenol (2 g, 18.326 mmol, 1 equiv.) in 20 ml of dry DMF, NaHCO3
(6.15 g, 73.307 mmol, 4 equiv.) was added, followed by drop wise addition of 2ꢀ
ethylhexylbromide (13.03 ml, 73.307 mmol, 4 equiv.) and the reaction mixture was heated at
100 °C for 12 h. The reaction mixture was cooled to room temperature, ethyl acetate and
water were added. The combined ethyl acetate layer was washed sequentially with water and
brine solution. The organic layer was then dried over Na2SO4, filtered and the solvent was
stripped off under reduced pressure. Purification by column chromatography (eluent: 20%
AcOEt/ pet. ether, Rf: 0.6) afforded 9 (3.41 g, 56%) as a liquid compound. IR (CHCl3) ν (cmꢀ
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1): 3341, 2956, 2925, 1738, 1617, 1577, 1242, 1169, 751; H NMR (400 MHz, CDCl3) δ:
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7.05ꢀ7.01 (t, J = 8.31 Hz, 1H), 6.27ꢀ6.25 (dd, J = 8.31 Hz, J = 1.96 Hz, 1H), 6.15 (s, 1H),
6.10ꢀ6.08 (dd, J = 7.82 Hz, J = 1.71 Hz, 1H), 4.64 (s, 1H), 3.25ꢀ3.11 (m, 4H), 1.81ꢀ1.79 (m,
9
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2H), 1.40ꢀ1.26 (m, 16H), 0.92ꢀ0.86 (m, 12H); C NMR (100 MHz, CDCl3) δ: 156.4, 150.0,
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129.7, 105.7, 102.0, 99.5, 56.3, 36.7, 30.6, 28.6, 23.9, 23.2, 14.0, 10.6; HRMS (ESI)
calculated [M+H]+ for C22H40ON: 334.3104, found 334.3104.
4-(Bis(2-ethylhexyl)amino)-2-hydroxybenzaldehyde (5b)10
Vilsmeier reagent was prepared by drop wise addition of phosphorous oxychloride (0.307 ml,
3.303 mmol, 1.1 equiv.) to anhydrous DMF (0.92 ml, 12.012 mmol, 4 equiv.) at 0 °C, and the
mixture was stirred for 5 min at the same temperature and then for 30 min at room
temperature. Compound 9 (1 g, 3.003 mmol, 1 equiv.) in 2 ml of DMF was added to the
Vilsmeier reagent drop wise and the mixture was heated at 70 °C for 6 h. Then the mixture
was cooled, poured into ice water and basicified with NaOH until pH 6 was reached. The
product was extracted with diethyl ether and the organic layer was washed sequentially with
water and brine solution. Ether layer was then dried over Na2SO4, filtered and the solvent was
stripped off under reduced pressure. Purification by column chromatography (eluent: 10%
AcOEt/ pet. ether, Rf: 0.5) afforded 5b (0.791 g, 73%) as a liquid compound. IR (CHCl3) ν
1
(cmꢀ1): 2957, 2926, 2744, 1727, 1629, 1558, 1459, 1225, 1133, 784; H NMR (400 MHz,
CDCl3) δ: 11.61(s, 1H), 9.49 (s, 1H), 7.26ꢀ7.24 (d, J = 8.80 Hz, 1H), 6.29ꢀ6.26 (dd, J = 8.80
Hz, J = 2.20 Hz, 1H), 6.08ꢀ6.07 (d, J = 2.20 Hz, 1H), 3.35ꢀ3.22 (m, 4H), 1.84ꢀ1.81 (m, 2H),
1.36ꢀ1.27 (m, 16H), 0.92ꢀ0.88 (m, 12H); 13C NMR (100 MHz, CDCl3) δ: 191.8, 164.0, 154.8,
134.9, 111.3, 105.3, 97.8, 56.3, 37.1, 30.5, 28.5, 23.8, 23.0, 14.0, 10.6; HRMS (ESI)
calculated [M+H]+ for C23H40O2N: 362.3052, found 362.3054.
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2-amino-6-(7-(bis(2-ethylhexyl)amino)-2-oxo-2H-chromen-3-yl)pyrimidin-4(1H)-one
(6b)
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Following the same procedure for synthesis of compound 6a and using 4ꢀ[bis(2ꢀ
ethylhexyl)amino]ꢀ2ꢀhydroxybenzaldehyde (5b), 6b was synthesized. Purification was
effected by column chromatography (eluent: 10% MeOH/ DCM, Rf: 0.4) to yield 6b (0.971
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g, 71%) as a yellow solid. mp: 198ꢀ200 C; IR (CHCl3) ν (cmꢀ1): 3308, 2955, 2921, 1722,
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1650, 1572, 1453, 1215, 893; H NMR (400 MHz, CDCl3) δ: 12.47 (s, 1H), 8.70 (s, 1H),
7.39ꢀ7.37 (d, J = 9.16 Hz, 1H), 7.11 (s, 1H), 6.62ꢀ6.60 (d, J = 8.55 Hz, 1H), 6.47 (s, 1H), 6.19
(s, 2H), 3.36ꢀ3.25 (m, 4H), 1.83 (m, 2H), 1.33ꢀ1.28 (m, 16H), 0.91ꢀ0.88 (m, 12H); 13C NMR
(100 MHz, CDCl3) δ: 160.8, 156.8, 154.7, 152.7, 144.2, 130.3, 110.5, 108.6, 100.9, 97.6,
56.5, 37.0, 30.4, 28.5, 23.7, 23.1, 14.0, 10.6; HRMS (ESI) calculated [M+H]+ for
C29H43O3N4: 495.3331, found 495.3330.
1-Benzyl-3-(6-(7-(bis(2-ethylhexyl)amino)-2-oxo-2H-chromen-3-yl)-4-oxo-1,4-
dihydropyrimidin-2-yl)urea (1d)
Following the same procedure for synthesis of compound 1a and using amine 6b and benzyl
isocyanate, 1d was synthesized. Purification was effected by column chromatography (eluent:
10% MeOH/ DCM, Rf: 0.5) to yield 1d (0.198 g, 78%) as a fluffy yellow solid. mp: 146ꢀ148
1
oC; IR (CHCl3) ν (cmꢀ1): 3746, 3218, 3131, 2957, 1727, 1666, 1586, 1453, 1235, 741; H
NMR (700 MHz, CDCl3) δ: 14.23 (s, 1H) (major protomer, 80%), 13.39 (s, 1H) (minor
protomer, 20%), 11.90 (s, 1H) (major protomer, 80%), 11.41 (s, 1H) (minor protomer, 20%),
10.73 (s, 1H) (major protomer, 80%), 10.36 (s, 1H) (minor protomer, 20%), 7.99 (s, 1H),
7.43ꢀ7.42 (d, J = 7.74 Hz, 2H), 7.36ꢀ7.35 (d, J = 9.03 Hz, 1H), 7.32ꢀ7.30 (t, J = 7.74 Hz, 2H),
7.23ꢀ7.21 (t, J = 7.31 Hz, 1H), 6.67ꢀ6.65 (dd, J = 9.03 Hz, J = 1.94 Hz, 1H), 6.49 (s, 1H),
6.41 (s, 1H), 4.70 (bs, 2H) (minor protomer, 20%), 4.55ꢀ4.54 (d, J = 5.81 Hz, 2H) (major
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protomer, 80%), 3.39ꢀ3.29 (m, 4H), 1.83ꢀ1.82 (m, 2H), 1.39ꢀ1.28 (m, 16H), 0.93ꢀ0.90 (m,
12H); 13C NMR (175 MHz, CDCl3) δ: 172.9, 160.0, 159.9, 156.9, 156.7, 156.1, 154.2, 153.2,
152.5, 145.6, 142.6, 139.1, 138.5, 130.3, 128.7, 128.3, 127.7, 127.6, 127.3, 126.8, 114.3,
110.9, 110.1, 108.1, 108.0, 103.1, 97.8, 97.5, 56.5, 56.4, 44.0, 43.3, 37.0, 36.9, 30.4, 28.5,
23.8, 23.0, 14.0, 13.9, 10.6; HRMS (ESI) calculated [M+H]+ for C37H50O4N5: 628.3855,
found 628.3857, 1255.7642 [2M+H]+.
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1-(6-(7-(Bis(2-ethylhexyl)amino)-2-oxo-2H-chromen-3-yl)-4-oxo-1,4-dihydropyrimidin-
2-yl)-3-(2-ethylhexyl)urea (1e)
Following the same procedure for synthesis of compound 1a and using amine 6b and 2ꢀ
ethylhexyl isocyanate, 1e was synthesized. Purification was effected by column
chromatography (eluent: 10% MeOH/ DCM, Rf: 0.5) to yield 1e (0.202 g, 77%) as a fluffy
o
yellow compound. mp: 66ꢀ68 C; IR (CHCl3) ν (cmꢀ1): 3747, 3131, 3109, 2955, 1723, 1696,
1502, 1270, 1177, 665; 1H NMR (400 MHz, CDCl3) δ: 14.25 (s, 1H) (major protomer, 80%),
13.54 (s, 1H) (minor protomer, 20%), 11.82 (s, 1H) (major protomer, 80%), 11.26 (s, 1H)
(minor protomer, 20%), 9.93 (s, 1H) (major protomer, 80%), 9.83 (s, 1H) (minor protomer,
20%), 8.29 (s, 1H) (minor protomer, 20%), 8.01 (s, 1H) (major protomer, 80%), 7.37ꢀ7.35
(m, 1H), 6.66ꢀ6.64 (d, J = 7.93 Hz, 1H), 6.50 (s, 1H), 6.45 (s, 1H), 3.40ꢀ3.29 (m, 4H), 3.27ꢀ
3.26 (m, 2H), 1.83 (m, 2H), 1.65 (m, 1H), 1.47ꢀ1.29 (m, 24H), 0.93ꢀ0.89 (m, 18H); 13C NMR
(100 MHz, CDCl3) δ: 172.8, 159.9, 156.9, 156.1, 154.3, 153.2, 145.5, 142.6, 130.2, 110.8,
108.5, 108.1, 103.1, 97.8, 56.5, 43.4, 39.0, 37.0, 30.7, 30.5, 28.7, 28.5, 24.0, 23.8, 23.0, 14.1,
14.0, 10.6; HRMS (ESI) calculated [M+H]+ for C38H60O4N5: 650.4626, found 650.4640,
1299.9207 [2M+H]+.
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ASSOCIATED CONTENT
Supporting Information
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Copies of 1H and 13C NMR spectra for all new compounds, studies on the selfꢀassembly of 1a
and 1d and singleꢀcrystal Xꢀray data of 1a. This material is available free of charge via the
Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
* gj.sanjayan@ncl.res.in
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
S.K, S.R.and A.S.K are thankful to CSIR, New Delhi for research fellowships. GJS thanks
the DST, New Delhi, for financial support.
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