Synthesis and photophysical properties of functionalized fluorescent 4H-chromenes and benzo[a]chromenophenazines as Fe3+ and Cu2+ ion sensor

Accepted Manuscript Title: Synthesis and photophysical properties of functionalized fluorescent 4H-chromenes and benzo[a]chromenophenazines as Fe3+ and Cu2+ ion sensor Authors: Gurusamy Harichandran, Parkunan Parameswari, Ponnusamy Shanmugam PII: DOI: Reference:

S0925-4005(18)31043-8 https://doi.org/10.1016/j.snb.2018.05.134 SNB 24790

To appear in:

Sensors and Actuators B

Received date: Revised date: Accepted date:

15-11-2017 10-5-2018 23-5-2018

Please cite this article as: Gurusamy Harichandran, Parkunan Parameswari, Ponnusamy Shanmugam, Synthesis and photophysical properties of functionalized fluorescent 4Hchromenes and benzo[a]chromenophenazines as Fe3+ and Cu2+ ion sensor, Sensors and Actuators B: Chemical https://doi.org/10.1016/j.snb.2018.05.134 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Synthesis and photophysical properties of functionalized fluorescent 4H-chromenes and benzo[a]chromenophenazines as Fe3+ and Cu2+ ion sensor

a

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Gurusamy Harichandrana,*, Parkunan Parameswaria, Ponnusamy Shanmugamb,*

Department of Polymer Science, University of Madras, Guindy Campus, Chennai 600025, India

b

Organic and Bioorganic Chemistry Division, CSIR-Central Leather Research Institute (CLRI),

Adyar, Chennai 600020, India E-mail: [email protected]

Synthesis of fluorescent 4H-chromenes and benzo[a]chromenophenazines via MCR is

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

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Highlights

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Graphical Abstract

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reported.

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A reusable Amberlite resin has been used as catalyst.

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Evaluation of photophysical properties revealed that these are blue emissive fluorescent materials.

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Both 4H-chromene derivative 5a and benzo[a]chromenophenazine 6a have been found to be metal ion sensors for the detection of Fe3+ and Cu2+ ions.

Abstract An efficient Amberlite resin catalyzed one-pot, multicomponent reaction of

1,2-

phenylenediamine, 2-hydroxynaphthalene-1,4-dione, 2-hydroxy benzaldehydes, and 1,3as solvent to obtain the fluorescent 4H-chromenes and

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diketones in EtOH/H2O (1/1, v/v)

benzo[a]chromenophenazines has been achieved. The structure of compounds 5g and 6e were confirmed from single crystal XRD analysis. Photophysical properties such as solvatochromism, absorption, emission, Stocks shift and quantum yield have been evaluated. The emission spectra suggested that these are blue emissive fluorescent compounds. Further, 4H-chromenes and

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benzo[a]chromenophenazines act as fluorescent chemosensor for the detection of metal-ions.

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Among the screened compounds, 4H-chromene derivative 5a and benzo[a]chromenophenazine

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6a have been found to be good metal ion sensors for the detection of Fe3+ and Cu2+ ions.

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Keywords

Amberlite resin; Multicomponent reactions; Phenazine derivatives; Photophysical properties;

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Introduction

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Metal ion sensor

Multicomponent reactions (MCRs) are simple and convergent atom-economic synthesis

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approach that offers advantages over conventional multi-step reaction for the synthesis of complex molecules without isolation of intermediates there by significantly reducing the wastage

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of chemical, time, and cost [1]. Furthermore, the MCRs play a crucial role in the syntheses bioactive molecules [2]. Phenazine like compounds are commonly found in natural and synthetic products and display a wide range of biological properties such as antimalarial [3,4], antiplatelet [5], antitumor [6], fungicidal [7], trypanocidal [8] and antituberculosis [9,10] activities.

Similarly, chromene containing compounds are employed as pharmaceuticals [11] including as antifungal (Asphodelin A) [12,13] and as antimicrobial (Uvafzlelin) agents [14] (Fig. 1). Thus, compounds having phenazine and chromene core attract attention in drug discovery [15, 16].

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Fig. 1.

Fluorescent phenazines have been used as photo-sensitizers in photodynamic therapy [17], emitters for electroluminescence devices [18], organic semiconductors [19], and electrochemical and biosensors [20]. Chromenes also play a major role in the development of fluorescent dyes for synthetic fibers, daylight fluorescent pigments and electro photographic and

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electroluminescent devices [21-23].

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Amberlite IRA-400 Cl is a heterogeneous basic anion exchange resin catalyst used

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inseveral organic transformations [24-26].The advantages of Amberlite IRA-400 Cl resin is its

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commercial availability, low cost and absence of side reactions. We have been working on the

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development of new synthesis protocols based on heterogeneous Amberlite IRA-400 Cl resin

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catalyzed organic reactions[27-30].

Acid catalyzed synthesis of benzo[a]chromenophenazines from o-phenylenediamine, 2-

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hydroxynaphthalene-1,4-dione, arylaldehydes and 1,3-diketones are reported [31-34]. However,

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syntheses of 4H-chromenes and benzo[a]chromenophenazines using both anion and cation exchanged Amberlite resin as catalysts are unknown in the literature. Thus, we have attempted

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the synthesis of title compounds from a four component reaction of o-phenylenediamine, 2hydroxy naphthalene-1,4-dione, salicylaldehyde, and 1,3-diketones using anion and cation exchanged Amberlite resin as catalysts (Scheme 1).We have studied the photophysical properties and possible sensor applications of these compounds.

Scheme 1. 2.

Experimental

2.1.

Materials and methods

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Chemicals were procured from SRL, Alfa Aesar, Sigma Aldrich and used as received. Melting points were determined in open capillaries and are uncorrected. FT-IR spectra were recorded on a Thermo Mattson Satellite FT-IR spectrophotometer by KBr pellet method and 1H and 13C NMR spectra were recorded on a Bruker ultra shield spectrometer (400 and 100 MHz) or Bruker ultra shield spectrometer (300 and 75 MHz) in CDCl3 and/or DMSO-d6 solvent using

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TMS as internal standard. Mass spectra were recorded on JEOL GCMATE II GC-MS mass

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spectrometer. Chromatographic purification was conducted using a column packed with silica

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gel and solvent as specified. Solvents used for purification were of commercial grade and were

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purified before used.

The absorption spectra were recorded using Shimadzu UV-1601 spectrophotometer over

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the range of 200−1100 nm. Steady-state fluorescence spectra were recorded using Fluoromax 4

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(Horiba JobinYvon) spectrofluorimeter equipped with Xe-150 W lamp. The emission quantum

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yields (Φf) were obtained by comparing corrected peak areas of the sample and that of the standard (coumarin 153 in methanol, Φf = 0.45), using the following equation:

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Qs = QR . Is/IR . ODR/ODs .ns2/n2R where Q is the quantum yield, I is the integrated intensity, OD is the optical density, and n is the

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refractive index. The subscript R refers to coumarin 153. Preparation of the stock solutions for fluorescence measurement

The stock solutions (1.0×10−3 M) of metal ions (ferric chloride, copper chloride) were prepared in double-distilled water. The stock solution (1.0×10-3 M) of compounds 5a and 6a were prepared in CH3CN.

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Procedure for metal ion sensing by fluorescence spectroscopy 1.0×10-4 M solution of 5a or 6a prepared in CH3CN/water (9:1) was taken in a quartz optical cell. The selectivity of metal ion sensor was tested for cations such as Pb2+, Co2+, Fe2+, Ni2+, Mn2+, Cu2+, Zn2+, Cd2+, Ag+, Hg2+ and Fe3+ at a fixed concentration (1.0×10-4 M). Among the tested cations Fe3+ and Cu2+ strongly affects the emission property of compound 5a and 6a

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(figure 7, table 5). In titration experiments, 1.0×10-4 M solution of 5a or 6a, various amount of

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Fe(III) or Cu(II) ranging from 0-200 µM from the stock solution was added and the experimental

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LOD was calculated.

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LOD was calculated based on the standard deviation of the response (SD) and the slope of the calibration curve (S) at levels approximating the LOD according to the formula:

General procedure for the preparation of 4H-chromene derivatives 5

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2.2.

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LOD = 3(SD/S)

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A mixture of o-phenylenediamine 1 (1.0 mmol), 2-hydroxynaphthalene-1,4-dione 2 (1.0 mmol) and Amberlite resin (H+ or Cl-) (60 mole %) in EtOH/H2O (1/1, v/v) was stirred at 80 °C

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until an orange precipitate of benzo[a]phenazin-5-ol was formed. Then, 2-hydroxy benzaldehydes 3(a-c) (1.0 mmol) or 2-hydroxy-1-naphthaldehyde 3d (1.0 mmol) and 1,3-

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dicarbonyls 4(a-c) (1.0 mmol) were added to the above reaction mixture and the stirring continued until starting materials disappeared. After completion of the reaction (as indicated by TLC), the reaction mixture was cooled and diluted with chloroform (10 mL) and the catalyst was removed by filtration. The filtrate was concentrated under reduced pressure and the resulting

crude mixture was purified by silica gel column chromatography using chloroform as eluent to afford corresponding products. The isolated compounds were characterized by FTIR, 1H NMR, 13

C NMR, HRMS and X-ray crystallographic study for selected compounds. The 13C NMR data

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of 4H-chromenes (5b,c,d,e,f,i,k,l) and benzo[a]chromenophenazines (6c,f) could not be recorded due to their low solubility which demands a large number of scans. Attempts to prepare NMR samples of 4H-chromenes (5b,c,d,e,f,i,k,l) and benzo[a]chromenophenazines (6c,f) in other solvent such as DMSO-d6 also resulted in poor solubility and only provided turbid solutions.

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2.3. Spectroscopic characterization of selected compounds

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9-(5-hydroxy-benzo[a]phenazin-6-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (5a)

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Orange solid; mp 236-238 °C; Rf 0.74 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax:

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3422, 2954, 1650, 1623, 1592, 1491, 1456, 1386, 1296, 1233, 1191, 1149, 1059, 862, 761 cm-1; 1H NMR (400 MHz, CDCl3): δH (ppm) 0.65 (3H, s, CH3), 1.06

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(3H, s, CH3), 2.14-2.35 (2H, m, CH2), 2.52-2.58 (2H, m, CH2), 5.59 (1H, s, CH), 6.56-6.70 (1H,

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m, ArH), 6.84 (1H, d, J = 4 Hz, ArH), 6.94-6.98 (1H, m, ArH), 7.04-7.06 (1H, m, ArH), 7.56-

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7.62 (2H, m, ArH), 7.67-7.77 (2H, m, ArH), 7.82-7.85 (1H, m, ArH), 8.07-8.09 (1H, m, ArH), 8.49-8.51 (1H, m, ArH), 9.18-9.20 (1H, m, ArH), 10.24 (1H, s, OH);

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C NMR (100 MHz,

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CDCl3): δC (ppm) 25.8, 28.2, 29.0, 31.4, 40.9, 48.9, 110.9, 114.2, 117.9, 123.1, 123.3, 123.8, 124.5, 126.4, 127.0, 127.1, 127.4, 127.6, 128.1, 128.3, 128.8, 129.1, 130.3, 138.6, 139.6, 140.6,

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142.6, 142.5, 150.7, 152.1, 168.0, 199.7; HRMS m/z (ESI) calculated for C31H24N2O3 [M]+ 472.5339; found 472.5337. 9-(5-hydroxybenzo[a]phenazin-6-yl)-3,3-dimethyl-7-bromo-2,3,4,9-tetrahydro-1H-xanthen-1one (5b)

Orange solid; mp 248-251 °C; Rf 0.68 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax: 3067, 2958, 2870, 1725, 1665, 1598, 1474, 1414, 1290, 1206, 1176, 1046, 928, 815, 767 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 0.73 (3H, s, CH3), 1.13

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(3H, s, CH3), 2.24 (1H, d, J = 16 Hz, CH2), 2.40 (1H, d, J = 16 Hz, CH2), 2.64 (2H, d, J = 4 Hz, CH2), 5.81 (1H, s, CH), 6.86 (1H, d, J = 8 Hz, ArH), 7.08-7.12 (2H, m, ArH), 7.82-7.91 (4H, m, ArH), 8.73-8.38 (3H, m, ArH), 9.27-9.32 (1H, m, ArH), 10.87 (1H, s, OH); HRMS m/z (ESI) calculated for C31H23BrN2O3 [M]+ 551.4299; found 551.4298.

9-(5-hydroxy-benzo[a]phenazin-6-yl)-3,3-dimethyl-7-nitro-2,3,4,9-tetrahydro-1H-xanthen-1-one

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(5c)

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Yellow solid; mp 232-234 °C; Rf 0.63 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax:

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3326, 3125, 1742, 1640, 1583, 1461, 1385, 1293, 1251, 1100, 1061, 804, 766

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cm-1; 1H NMR (400 MHz, CDCl3): δH (ppm) 0.92 (3H, s, CH3), 1.08 (3H, s, CH3), 2.13-2.26 (2H, m, CH2), 2.49-2.60 (2H, m, CH2), 6.13 (1H, s, CH), 7.07 (1H, d, J = 8 Hz,

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ArH), 7.81-8.12 (6H, m, ArH), 8.29-8.53 (3H, m, ArH), 9.31 (1H, d, J = 8 Hz, ArH), 12.89 (1H,

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s, OH); HRMS m/z (ESI) calculated for C31H23N3O5 [M]+ 517.5314; found 517.5312.

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9-(5-hydroxy-benzo[a]phenazin-6-yl)-2,3,4,9-tetrahydro-1H-xanthen-1-one (5d) Yellow solid; mp 246-249 °C; Rf 0.77 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax:

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3423, 2945, 1629, 1598, 1483, 1457, 1418, 1352, 1326, 1236, 1171, 1667, 806, 755 cm-1; 1H NMR (400 MHz, CDCl3): δH (ppm) 2.11-2.19 (2H, m, CH2), 2.42-

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2.58 (2H, m, CH2), 2.98 (1H, t, J = 12 Hz, CH2), 3.24 (1H, dd, J = 16, 16 Hz, CH2), 5.86 (1H, s, CH), 6.79-7.07 (3H, m, ArH), 7.72-7.90 (5H, m, ArH), 8.23-8.42 (3H, m, ArH), 9.28-9.31 (1H, m, ArH), 11.58 (1H, s, OH); HRMS m/z (ESI) calculated for C29H20N2O3 [M]+ 444.4807; found 444.4803.

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9-(5-hydroxy-benzo[a]phenazin-6-yl)-7-bromo-2,3,4,9-tetrahydro-1H-xanthen-1-one (5e) Orange solid; mp 230-232 °C; Rf 0.67 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax: 3147, 2936, 1721, 1630, 1600, 1474, 1418, 1300, 1237, 1171, 1056, 922, 819, 766 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 2.11-2.21 (2H, m, CH2), 2.412.49 (2H, m, CH2), 2.96-2.99 (1H, m, CH2), 3.22 (1H, d, J = 4 Hz, CH2), 5.81 (1H, s, CH), 6.79

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(1H, d, J = 8 Hz, ArH), 7.13-7.16 (1H, m, ArH), 7.73-7.83 (5H, m, ArH), 8.19-8.32 (3H, m,

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C29H19BrN2O3 [M]+ 523.3768; found 523.3766.

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ArH), 9.29-9.31 (1H, m, ArH), 10.41 (1H, s, OH); HRMS m/z (ESI) calculated for

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9-(5-hydroxy-benzo[a]phenazin-6-yl)-7-nitro-2,3,4,9-tetrahydro-1H-xanthen-1one (5f)

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Yellow solid; mp 258-261 °C; Rf 0.67 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax:

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3430, 2925, 1744, 1647, 1620, 1593, 1495, 1478, 1408, 1339, 1224, 1174, 1060,

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831, 768 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm)) 2.11-2.20 (2H, m, CH2), 2.43-2.55 (2H, m, CH2), 2.95-3.02 (2H, m, CH2), 5.92 (1H, s, CH), 7.16 (1H, d, J = 8 Hz, ArH), 7.72-7.88 (6H,

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m, ArH), 8.28-8.48 (3H, m, ArH), 9.32 (1H, d, J = 8 Hz, ArH); HRMS m/z (ESI) calculated for C29H19N3O5 [M]+ 489.4783; found 489.4780.

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7-(5-Hydroxy-benzophenazine-6-yl)-6H,7H-chromeno[4,3-b]chromene-6-one (5g) Red crystalline solid; mp 244-246 °C; Rf 0.69 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax: 3417, 3217, 1682, 1641, 1609, 1571, 1477, 1328, 1243, 1182, 1106, 1055, 876, 810, 759 cm-1; 1H NMR (400 MHz, CDCl3): δH (ppm) 5.88 (1H, s,

CH), 6.77 (1H, t, J = 8 Hz, ArH), 6.95 (1H, d, J = 8 Hz, ArH), 7.07 (1H, t, J = 8 Hz, ArH), 7.257.29 (2H, m, ArH), 7.34-7.40 (1H, m, ArH), 7.48-7.60 (3H, m, ArH), 7.69-7.83 (3H, m, ArH), 8.05-8.07 (1H, m, ArH), 8.23 (1H, d, J = 8 Hz, ArH), 8.52 (1H, d, J = 8 Hz, ArH), 9.18 (1H, d, J 13

C NMR (100 MHz, CDCl3): δC (ppm) 30.4, 101.4, 113.9,

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= 8 Hz, ArH), 9.62 (1H, s, OH);

114.5, 116.0, 121.7, 123.9, 123.9, 127.0, 127.3, 127.3, 128.23, 128.3, 128.9, 131.2, 138.7, 142.3, 150.3, 151.2, 152.5, 157.2; HRMS m/z (ESI) calculated for C32H18N2O4 [M]+ 494.4963; found 494.4960.

7-(5-Hydroxy-benzophenazine-6-yl)-9-bromo-6H,7H-chromeno[4,3-b]chromene-6-one (5h)

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Red solid; mp 236-239 °C; Rf 0.62 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax:

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3416, 3215, 1728, 1674, 1640, 1609, 1487, 1457, 1394, 1279, 1220, 1162, 1107,

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861, 802, 760 cm-1; 1H NMR (400 MHz, CDCl3): δH (ppm) 5.89(1H, s, CH),

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7.15 (1H, m, ArH), 7.21-7.26 (2H, m, ArH), 7.35(1H, d, J = 8 Hz, ArH), 7.45(1H, t, J = 7.8 Hz, ArH), 7.58(1H, t, J = 8 Hz, ArH), 7.64-7.67 (2H, m, ArH),7.78-7.87 (3H, m, ArH), 8.15-8.17

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(1H, m, ArH),8.26 (1H, d, J = 8 Hz, ArH), 8.59(1H, d, J = 8 Hz, ArH), 9.27(1H, d, J = 8 Hz,

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ArH), 9.60 (1H, s, OH); 13C NMR (100 MHz, CDCl3):δC (ppm) 31.3, 102.2, 117.1, 117.4, 122.7,

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124.9, 128.6, 129.9, 131.1, 132.5, 139.9, 140.0, 140.7, 141.0, 141.4, 141.9, 143.0, 147.1, 150.5, 151.3, 152.2, 153.8, 157.2, 157.9; HRMS m/z (ESI) calculated for C32H17BrN2O4 [M]+ 573.3924;

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found 573.3920.

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7-(5-Hydroxy-benzophenazine-6-yl)-9-nitro-6H,7H-chromeno[4,3-b]chromene-6-one (5i) Orange solid; mp 264-266 °C; Rf 0.64 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax: 3423, 1703, 1620, 1524, 1484, 1416, 1350, 1294, 1249, 1158, 1089, 1040, 1052, 834, 758 cm-1; 1H NMR (400 MHz, CDCl3): δH (ppm) 6.26 (1H, s, CH), 7.16 (1H, d, J = 8 Hz, ArH), 7.31 (1H, t, J = 8 Hz, ArH), 7.45-7.54 (2H, m, ArH), 7.93-8.03 (4H,

m, ArH), 8.15 (1H, d, J = 8 Hz, ArH), 8.26 (1H, d, J = 8 Hz, ArH), 8.40-8.46 (2H, m, ArH), 9.39(1H, d, J = 8 Hz, ArH), 10.26 (1H, s, OH); HRMS m/z (ESI) calculated for C32H17N3O6 [M]+ 539.4939; found 539.4937.

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12-(5-hydroxy-benzo[a]phenazin-6-yl)-9,9-dimethyl-8,9,10,12-tetrahydro-benzo[a]xanthen-11one (5j)

Orange solid; mp 236-239 °C; Rf 0.71 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax: 3425, 2957, 2872, 1748, 1654, 1608, 1595, 1496, 1460, 1390, 1276, 1182, 1146, 1057, 754 cm-1; 1H NMR (400 MHz, CDCl3): δH (ppm) 0.71 (3H, s, CH3), 1.13

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(3H, s, CH3), 2.25-2.46 (2H, m, CH2), 2.63-2.73 (2H, m, CH2), 6.22 (1H, s, CH), 7.17 (1H, t, J =

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7.2 Hz, ArH), 7.24-7.28 (1H, m, ArH), 7.37 (1H, d, J = 8 Hz, ArH), 7.57-7.74 (5H, m, ArH),

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7.80-7.85 (2H, m, ArH), 7.94-7.97 (1H, m, ArH), 8.07-8.10 (1H, m, ArH), 8.65 (1H, d, J = 12 13

C NMR (100 MHz, CDCl3): δC

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Hz, ArH), 9.19 (1H, d, J = 8 Hz, ArH), 10.49 (1H, s, OH);

(ppm) 26.8, 27.9, 29.3, 32.5, 41.8, 50.0, 111.9, 116.3, 117.7, 118.4, 123.0, 124.3, 124.5, 124.8,

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127.0, 128.1, 128.2, 128.4, 128.5, 129.1, 129.6, 129.7, 129.9, 131.0, 131.4, 131.5, 139.5, 140.5,

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141.6, 143.7, 149.4, 152.4, 168.9, 200.8; HRMS m/z (ESI) calculated for C35H26N2O3 [M]+

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522.5925; found 522.5923.

12-(5-hydroxy-benzo[a]phenazin-6-yl)-8,9,10,12-tetrahydro-benzo[a]xanthen-11-one (5k)

A

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Orange solid; mp 196-199 °C; Rf 0.67 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax: 3418, 3126, 1720, 1657, 1623, 1595, 1495, 1469, 1397, 1239, 1193, 1142, 1055, 811, 752 cm-1; 1H NMR (300 MHz, CDCl3): δH (ppm) 1.84-1.93 (2H, m,

CH2), 2.05-2.13 (1H, m, CH2), 2.50-2.53 (2H, m, CH2), 2.82-2.86 (2H, m, CH2), 6.22 (1H, s, CH), 7.19 (1H, t, J = 7.5 Hz, ArH), 7.28 (1H, d, J = 7.2 Hz, ArH), 7.40 (1H, d, J = 8 Hz, ArH), 7.58-7.79 (6H, m, ArH), 7.82-7.94 (2H, m, ArH), 7.96-7.97 (1H, m, ArH), 8.11 (1H, d, J = 7.8

Hz, ArH), 8.65(1H, d, J = 8 Hz, ArH), 9.21 (1H, d, J = 7.8 Hz, ArH), 10.69 (1H, s, OH); HRMS m/z (ESI) calculated for C33H22N2O3 [M]+ 494.5394; found 494.5392.

SC RI PT

7-(5-Hydroxy-benzophenazine-6-yl)-6H,7H-benzochromeno[4,3-b]chromene-6-one (5l) Red solid; mp 209-211 °C; Rf 0.61 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax: 3423, 3223, 1674, 1653, 1610, 1495, 1458, 1399, 1319, 1273, 1230, 1072, 863, 809, 759 cm−1; 1H NMR (400 MHz, CDCl3):δH (ppm) 6.51 (1H, s, CH), 7.23 (1H, d, J = 8 Hz, ArH), 7.32-7.39 (2H, m, ArH), 7.48 (1H, t, J = 8 Hz, ArH), 7.58-7.67 (5H, m,

U

ArH), 7.72-7.78 (2H, m, ArH), 7.84-7.97 (3H, m, ArH), 8.07 (1H, d, J = 8 Hz, ArH), 8.36 (1H,

N

d, J = 8 Hz, ArH), 8.68 (1H, d, J = 8 Hz, ArH), 9.20 (1H, d, J = 8 Hz, ArH), 9.87 (1H, s, OH);

A

HRMS m/z (ESI) calculated for C36H20N2O4 [M]+ 544.5550; found 544.5554.

M

16-(2-hydroxy-5-phenyl)-3,3-dimethyl-2,3,4,16-tetrahydro-1H-benzo[a]chromeno[2,3c]phenazin-1-one (6a)

D

Yellow solid; mp 268-270 °C; Rf 0.43 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax:

TE

3432, 2955, 1668, 1619, 1471, 1374, 1274, 1204, 1167, 1044, 1027, 806, 767

EP

cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 1.24 (6H, d, J = 1.4 Hz, (CH3)2), 2.36-2.45 (2H, m, CH2), 2.80-2.94 (2H, m, CH2), 6.08 (1H, s, CH), 6.70-6.74 (1H, m, ArH),

CC

6.97-7.07 (3H, m, ArH), 7.81-7.92 (4H, m, ArH), 8.28-8.39 (3H, m, ArH), 9.31-9.33 (1H, m, ArH), 10.71 (1H, s, OH);

13

C NMR (100 MHz, CDCl3): δC (ppm) 26.9, 27.7, 29.5, 32.6, 41.2,

A

50.7, 114.8, 115.8, 118.9, 120.7, 122.0, 125.5, 126.5, 127.9, 128.1, 128.3, 128.8, 129.6, 129.9, 130.3, 130.3, 131.0, 132.6, 140.9, 140.9, 141.5, 148.3, 153.9, 164.3, 196.6; HRMS m/z (ESI) calculated for C31H24N2O3 [M]+ 472.5339; found 472.5337.

16-(2-hydroxy-5-bromophenyl)-3,3-dimethyl-2,3,4,16-tetrahydro-1H-benzo[a]chromeno[2,3-

SC RI PT

c]phenazin-1-one (6b) Yellow solid, mp 252-254 °C; Rf 0.45 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax: 3423, 2966, 1745, 1665, 1619, 1597, 1472, 1370, 1276, 1204, 1175, 1046, 1028, 767 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm)1.24 (6H, d, J = 4.4 Hz, (CH3)2), 2.42-2.43 (2H, m, CH2), 2.85-2.90 (2H, m, CH2), 5.94 (1H, s, CH), 6.86 (1H, d, J = 8

U

Hz, ArH), 7.08-7.10 (2H, m, ArH), 7.79-7.85 (4H, m, ArH), 8.23-8.31 (3H, m, ArH), 9.21 (1H,

N

d, J = 8 Hz, ArH), 10.82 (1H, s, OH); 13C NMR (100 MHz, CDCl3): δC (ppm) 27.1, 27.4, 29.7,

A

32.6, 41.2, 112.7, 114.3, 114.9, 120.8, 122.1, 125.4, 126.2, 127.7, 128.9, 129.7, 129.9, 130.2,

M

130.32, 130.9, 131.1, 134.3, 140.5, 140.6, 141.4, 147.5, 148.4, 153.3, 164.6, 196.6; HRMS m/z (ESI) calculated for C31H23BrN2O3 [M]+ 551.4299; found 551.4298.

TE

c]phenazin-1-one (6c)

D

16-(2-hydroxy-5-nitrophenyl)-3,3-dimethyl-2,3,4,16-tetrahydro-1H-benzo[a]chromeno[2,3-

EP

Yellow solid; mp 272-275 °C; Rf 0.45 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax: 3418, 2963, 1666, 1620, 1580, 1511, 1466, 1413, 1370, 1294, 1261, 1154, 1093,

CC

764 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm)1.19 (6H, d, J = 8 Hz, (CH3)2),

2.30-2.39 (2H, m, CH2), 2.80 (1H, d, J = 16 Hz, CH2), 2.95 (1H, d, J = 16 Hz, CH2), 5.98 (1H, s,

A

CH), 6.96 (1H, d, J = 12 Hz, ArH), 7.94-7.96 (6H, m, ArH), 8.28-8.38 (3H, m, ArH), 9.30 (1H, d, J = 8 Hz, ArH), 12.06 (1H, s, OH); HRMS m/z (ESI) calculated for C31H23N3O5 [M]+ 517.5314; found 517.5312.

16-(2-hydroxy-5-bromophenyl)-2,3,4,16-tetrahydro-1H-benzo[a]chromeno[2,3-c]phenazin-1one (6e)

SC RI PT

Yellow crystalline solid; mp 244-246 °C; Rf 0.37 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax: 3451, 2943, 1745, 1665, 1619, 1598, 1474, 1411, 1370, 1202, 1186, 1049, 768 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 2.22-2.29 (2H, m, CH2), 2.48-2.63 (2H, m, CH2), 3.08-3.15 (2H, m, CH2), 6.00 (1H, s, CH), 6.86 (1H, d, J = 8.8 Hz, ArH), 7.04-7.10 (2H, m, ArH), 7.83-7.90 (4H, m, ArH), 8.27-8.38 (3H, m, ArH), 9.21 (1H, m,

U

ArH), 10.79 (1H, s, OH); 13C NMR (100 MHz, CDCl3): δC (ppm) 20.5, 27.0, 27.5, 36.9, 112.8,

N

114.9, 115.5, 120.7, 122.2, 125.5, 126.2, 127.9, 129.0, 129.7, 130.4, 130.7, 131.1, 131.2, 134.4,

A

140.6, 140.8, 141.4, 141.5, 148.3, 153.4, 166.3, 197.0; HRMS m/z (ESI) calculated for

M

C29H19BrN2O3 [M]+ 523.3768; found 523.3766.

16-(2-hydroxy-5-nitrophenyl)-2,3,4,16-tetrahydro-1H-benzo[a]chromeno[2,3-c]phenazin-1-one

D

(6f)

TE

Yellow solid; mp 270-273 °C; Rf 0.37 (MeOH:CHCl3, 1:9); FT-IR (KBr) νmax:

EP

3447, 2965, 2931, 1744, 1662, 1619, 1598, 1513, 1497, 1473, 1401, 1370, 1292, 1256, 1188, 834, 771 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 2.26-2.30 (2H,

CC

m, CH2), 2.48-2.62 (2H, m, CH2), 2.92-3.00 (1H, m, CH2), 3.16-3.22 (1H, m, CH2), 6.07 (1H, s, CH), 7.03 (1H, d, J = 8 Hz, ArH), 7.91-7.98 (6H, m, ArH), 8.32-8.39 (3H, m, ArH), 9.37 (1H, d,

A

J = 8 Hz, ArH), 12.07 (1H, s, OH); HRMS m/z (ESI) calculated for C29H19N3O5 [M]+ 489.4783; found 489.4781. Results and discussion

To accomplish the objectives, initially a one-pot four-component condensation of equimolar

amounts

of

o-phenylenediamine

1,

2-hydroxynaphthalene-1,4-dione

2,

salicylaldehyde 3 and dimedone 4 was considered for the preparation ofcompound 5a. Thus, two

SC RI PT

parallel experiments one in water and other in ethanol as solvent by sequential addition of reactants and without any catalyst at 80 °C for 5 h were carried out. However, no desired product 5a was observed (Table 1, entries 1 and 2). Then, the above experiments were repeated in the presence of Amberlite IRA-400 Cl resin (0.5 g, 150 mol%) as catalyst at 80 °C and the reaction afforded compound 5a in 46% and 61% yields, respectively (Table 1, entries 3 and 4). To

U

improve the yield of the product and to optimize the conditions: the solvent, Amberlite IRA-400

N

Cl resin catalyst load and reaction temperature were varied. When the experiment was carried

A

out using EtOH/H2O (1/1, v/v) as a mixed solvent at 80 °C (Table 1, entry 5) the reaction was

M

completed in 3h and afforded an improved yield (90%). The optimum yield was obtained with 0.2 g (60 mol %) of the catalyst. A further increase of Amberlite IRA-400 Cl resin up to 0.5 g

D

(150 mol %) did not have any significant effect on the product yield or reaction time (Table 1,

TE

entries 5-8). Increasing the temperature to 100 °C, no significant change in the product yields

EP

was observed. However, decrease in temperature leads to decreasing the product yield to trace (Table 1, entries 9 and 10). The reaction did not proceed at room temperature (Table 1, entry 11).

CC

Finally, the optimum reaction condition was found to be 0.2 g (60 mol %) of Amberlite IRA-400

A

Cl catalyst in EtOH/H2O (1/1, v/v) at 80 °C (Table 1, entry 7). Under optimized conditions, using another Amberlite IR-120 H+ resin (0.2 g, 60 mol%)

catalyst in EtOH/H2O (1/1, v/v) at 80 °C, the reaction was completed in 3h. However, a mixture of products 5a and 6a was obtained (Table 1, entry 12). The structure assignment of both the

products 5a and 6a were derived from spectroscopic analysis such as FTIR, 1H NMR, 13C NMR and HRMS. Table 1.

explored

for

the

synthesis

of

variety

SC RI PT

With optimization conditions in hand, the scope and efficiency of the reaction were of

substituted

4H-chromenes

and

benzo[a]chromenophenazines. Thus, reactions of o-phenylenediamine 1, 2-hydroxynaphthalene1,4-dione 2, salicylaldehyde 3(a-c) or

2-hydroxy-1-naphthaldehyde 3d and 1,3-dicarbonyl

compounds 4(a-c) were carried out. All the reactions underwent smoothly to afford only

U

4H-chromenes 5(a–l) in excellent yield using Amberlite IRA 400 Cl- resin as catalyst. However,

N

when Amberlite IR 120 H+ resin was used as catalyst, the reaction afforded a mixture of products

A

of 4H-chromenes 5(a-l) in 33-89% and benzo[a]chromenophenazines 6(a-f) in 37-49% yield and

M

the results are presented in Table 2. Table 2.

D

As shown in Table 2, it has been observed that the reaction using IRA- 400 Cl- resin as

TE

catalyst afforded only 4H-chromenes 5(a-l). Reaction of o-phenylenediamine 1, 2-hydroxy

EP

naphthalene-1,4-dione 2, dimedone 4a as an active methylene compound and salicylaldehyde 3(a-c) afforded compounds 5a (90%), 5b (86%) and 5c (84%), respectively (Table 2, entries 1-

CC

3). Using 1,3-cyclohexanedione 4b as an active methylene reactant, an excellent yield of products (85-92%) was obtained (Table 2, entries 4-6). Similarly, the reaction between

A

o-phenylenediamine

1,

2-hydroxynaphthalene-1,4-dione

2,

salicylaldehyde

3(a-c)

and

4-hydroxycoumarin 4c afforded compounds 5(g-i) in good yield (Table 2, entries 7-9). Further, o-phenylenediamine 1, 2-hydroxynaphthalene-1,4-dione 2, 2-hydroxy-1-naphthaldehyde 3d and

1,3-dicarbonyl compounds 4(a-c) afforded the expected products of 5(j-l) in good yields (Table 2, entries 10-12). The reaction in the presence of IR-120 H+ resin as catalyst provided both 4H-chromenes

SC RI PT

5 and benzo[a]chromenophenazines 6 as a mixture of products (Table 2). The reaction involving o-phenylenediamine1, 2-hydroxynaphthalene-1,4-dione 2, salicylaldehyde 3(a-c) or 2-hydroxy1-naphthaldehyde 3d and dimedone 4a afforded compounds 5a in 52% yield and 6a in 37% yield (Table 2, entry 1). Similarly, the reaction of o-phenylenediamine 1, 2-hydroxynaphthalene1,4-dione 2, salicylaldehyde 3a and 1,3-cyclohexanedione 4b yielded a single product 5d (Table

U

2, entry 4). The reaction between o-phenylenediamine 1, 2-hydroxynaphthalene-1,4-dione 2,

N

salicylaldehyde 3(a-c) or 2-hydroxy-1-naphthaldehyde 3d and 4-hydroxycoumarin 4c afforded

A

respective 4H-chromenes 5(g-i) in good yield (Table 2, entries 7-9). As expected, the reactions

M

between 1, 2, 3d and 1,3-dicarbonyls 4(a-c) afforded respective 4H-chromene derivatives 5(j-l) as major products (Table 2, entries 10-12). When the reaction was carried out with o-

D

phenylenediamine 1, 2-hydroxynaphthalene-1,4-dione 2, salicylaldehyde substituted with

TE

electron-withdrawing groups and 1,3-dicarbonyls 4a or 4b gave a mixture of products 5 and 6

EP

(Table 2, entries 2,3,5 and 6). All the newly synthesized compounds have been thoroughly characterized using spectroscopic techniques such as FTIR, 1H NMR,

13

C NMR, and HRMS.

CC

The structure assignment of new compounds 5g and 6e was further confirmed by single crystal X-ray analysis [35] (Fig. 2).

A

Fig. 2.

A plausible mechanism for the formation of compound 5, in presence of IRA-400 Cl

resin catalyst has been proposed in Scheme 2. At first, condensation of o-phenylenediamine1 and 2-hydroxynaphthalene-1,4-dione 2 forms benzo[a]phenazin-5-ol intermediate I. In another set of

Knoevenagel condensation of 2-hydroxybenzaldehyde 3a and dimedone4a under the influence of IRA 400 Cl resin catalyst affords intermediate II. Michael addition of benzo[a]phenazin-5-ol intermediate I to intermediate II followed by dehydration paving the way to ring closure affords

SC RI PT

the 4H-chromene 5a. Scheme 2.

The proposed mechanisms for the formation of compounds 5a and 6a with Amberlite IR120 H+ resin catalyst is outlined in Scheme 3. Initially, condensation of o-phenylenediamine 1 and 2-hydroxynaphthalene-1,4-dione 2 gives benzo[a]phenazin-5-ol I. Next two possible

U

pathways of mechanism (pathway-A and pathway-B) are possible. Pathway-A explains the

N

formation of compound 5a similar to scheme 2. In pathway B, the in situ generated

A

o-quinonemethide (o-QM) intermediate III is believed to form from benzo[a]phenazin-5-ol I

M

upon nucleophilic addition of salicylaldehyde. Subsequent Michael addition of intermediate III

Scheme 3.

TE

Photophysical Studies

D

to dimedone4a followed by dehydration affords benzo[a]chromenophenazines 6a.

Structural features of the compounds obtained prompted us to probe the photophysical

EP

properties of 4H-chromenes 5 and benzo[a]chromenophenazines 6. The photophysical properties

CC

such as absorption (λmax), emission (λem), molar extinction coefficient (ε), quantum yield (ɸf) and Stokes shift (Δῡ) [36-39] were evaluated for the synthesized compounds and the results are

A

presented in Table 3. Figures 3 and 4 show absorption and normalized emission spectra of compounds 5(a-l)

and 6(a-c & e, f), respectively. In the absorption spectra, two to three distinct and broad maxima for compounds 5(a-l) and 6(a-c & e, f) are found and the longest wavelength bands appeared between 414 to 422 nm with molar extinction coefficient (ε) ranging from 5000-9600 and 4400-

8600 L mol-1 cm-1, respectively. The emission spectra of compounds 5 and 6 showed emission maxima ranging from 462-498 nm and 450 to 468 nm, respectively. Stokes shifts and quantum yields of 4H-chromenes 5 and benzo[a]chromenophenazines 6 were determined using

SC RI PT

chloroform as solvent. Compounds 5 (a-l) showed lesser Stokes shift ranging from 2237-2876 cm-1, except compounds 5c, 5f and 5i. Compounds 6(a-f) also exhibit lesser Stokes shift ranging from 1530-2070 cm-1, except compound 6a, which showed a slightly higher shift of 3323 cm-1. Comparing compounds 5 and 6, the compound 5 series showed a relatively high quantum yield ranging from 1 to 10% and compounds 6 series were found to be only weakly fluorescent with

N

U

quantum yields ≤ 1%.

M

A

Fig. 3.

D

Fig. 4.

TE

Table 3.

EP

To demonstrate the influence of polarity of solvents [40] on the emission properties of 4H-chromenes 5 and benzo[a]chromenophenazines 6, the fluorescence spectra were recorded in solvents,

i.e.,

1,4-dioxane,

chloroform,

dichloromethane,

acetonitrile

and

CC

different

dimethylformamide. The emission maxima of compounds 5a and 6a gradually red shifted with

A

increase in the solvent polarity (Fig. 5). Fig. 5. Optical properties such as absorption, emission, extinction coefficient, quantum yield and Stokes shifts of compounds 5a and 6a are summarized in Table 4. The Lippert-Mataga [41-43]

plot for 5a and 6a are shown in Fig. 6. These plots show a good linear relationship (r2 = 0.9834 for 5a and r2 = 0.9811 for 6a, respectively) with a slope between the Stokes shift Δ

and the

solvent orientation polarizability Δf. These results suggest that the dipole-dipole interaction and

SC RI PT

dipole-induced dipole interactions between the solute and solvent are mainly responsible for the solvent-dependent fluorescence shift. Table 4. Fig. 6. Metal Ion Sensors

U

The photonics of the compounds 5a and 6a in the C = 1x10-4 M were examined in

N

CH3CN:H2O (9 : 1; v/v) by the addition of various metal ions in the concentration of 100 µM

A

such as Pb2+, Cu2+, Co2+, Fe3+, Fe2+, Ni2+, Mn2+, Zn2+, Cd2+, Ag+ and Hg2+. Upon addition of

M

Fe3+and Cu2+ to the solution of 5a and 6a, a prominent change was observed in fluorescence spectra. While the metal ions Pb2+, Co2+, Fe2+, Ni2+, Mn2+, Zn2+, Cd2+, Ag+ and Hg2+exhibit no

D

response under the same spectroscopic condition used for Fe3+and Cu2+ (Fig. 7).

TE

Fig. 7.

EP

From the fluorescence titration spectra (Fig. 8 and 9), it is observed that addition of up to 20 µM Fe3+, the fluorescence intensity gradually increases without any shift in emission

CC

maximum (480 nm). On 30 µM onwards, the emission intensity gradually starts to increase with the emission maximum shifting to longer wavelength region and finally at 200 µM of Fe3+, the

A

emission intensity attained maximum and the peak red shifted to 532 nm. On the other hand, the addition of Cu2+ (0-200 µM) to the solution of compounds 5a and 6a, the fluorescence emission intensity gradually increases and the emission maximum is slightly red shifted to 495 nm. The

detection limit calculated by reported methods [44] were found to be [Fe3+] 15 µM and [Cu2+] 20 µM for both compounds 5a and 6a. Fig. 8.

Table 5. CONCLUSION

SC RI PT

Fig. 9.

We have demonstrated an efficient Amberlite resin catalyzed one-pot, multicomponent reaction

for

the

synthesis

of

a

number

of

fluorescent

4H-chromenes

and

U

benzo[a]chromenophenazines. Photophysical properties such as solvatochromism, absorption,

N

emission, Stocks shift and quantum yield of the synthesized compounds have been evaluated.

A

The emission properties of the synthesized compounds suggested that these are blue emissive

M

fluorescent materials. Further, selected 4H-chromenes and benzo[a]chromenophenazines have been subjected as fluorescent chemosensor for the detection of metal-ions. Particularly, 4H-

D

chromene 5a and benzo[a]chromenophenazine 6a have been found to be good metal ion sensors

EP

TE

for the detection of Fe3+ and Cu2+ions.

ACKNOWLEDGMENTS

CC

One of the authors, P. P. acknowledges University of Madras for providing fellowship under UPE (II)–New Materials project. G.H. thanks the University of Madras for providing

A

infrastructure facilities. Thanks are due to Director, CSIR-CLRI and SAIF, IIT-M for NMR and single crystal measurements, respectively.

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SC RI PT

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free multicomponent synthesis of functionalized 4H-chromenes by using reusable,

[29]

heterogeneous Amberlite IRA-400 Cl resin as catalyst, Tetrahedron Lett., 56 (2015) 150154. G. Harichandran, S. David Amalraj, P. Shanmugam, Amberlite IRA-400 Cl resin catalyzed synthesis of secondary amines and transformation into N-((1H-indol-3-yl)

(heteroaryl) methyl)-N-heteroarylbenzenamines and bis-indoles via multicomponent reaction, J Saudi Chem. Soc., 22 (2018) 208-217 [30]

G. Harichandran, P. Parameswari, P. Shanmugam, An efficient solvent free Amberlite

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IRA-400 Cl resin mediated multicomponent synthesis and photophysical properties of fluorescent 4H-chromene derivatives, Dyes Pigments, 139 (2017) 541-548. [31]

J.M. Khurana, A. Chaudhary, A. Lumb, B. Nand, An expedient four-component domino protocol for the synthesis of novel benzo[a]phenazine annulated heterocycles and their photophysical studies, Green Chem., 14 (2012) 2321-2327. P.

Saluja,

A.

Chaudhary,

J.M.

Khurana,

Synthesis

of

novel

fluorescent

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[32]

N

benzo[a]pyrano[2,3-c]phenazine and benzo[a]chromeno[2,3-c]phenazine derivatives via

M. Rajeswari, G. Khanna,

A. Chaudhary, J.M. Khurana, Multicomponent domino

M

[33]

A

facile four-component domino protocol, Tetrahedron Lett., 55 (2014) 3431-3435.

process for the synthesis of some novel benzo[a]chromenophenazine fused ring systems

M.V. Reddy, K.R. Valasani, K.T. Lima, Y.T. Jeong, Tetramethyl guanidinium

EP

[34]

TE

1426-1432.

D

using H2SO4, phosphotungstic acid, and [NMP]H2PO4, Synth. Commun., 45 (2015)

chlorosulfonate ionic liquid (TMG IL): an efficient reusable catalyst for the synthesis of

CC

tetrahydro-1H-benzo[a]chromeno[2,3-c]phenazin-1-ones under solvent-free conditions and evaluation for their in vitro bioassay activity, New J. Chem., 3 (2015) 9931-9941.

A

[35]

CCDC 1485419 [5g] and CCDC 1485421 [6e] contain the supplementary crystallographic data. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif

[36]

T.J.J. Müller, In functional organic materials: syntheses, strategies and applications; Wiley-VCH: Weinheim, Germany, (2007) 179-223.

[37]

M. Teiber, S. Giebeler, T. Lessing, T.J.J. Müller, Efficient pseudo-five-component

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coupling-Fiesselmann synthesis of luminescent oligothiophenes and their modification, Org. Biomol. Chem., 11 (2013) 3541-3552. [38]

S. Periyaraja, P.Shanmugam, A.B. Mandal, T. Senthil Kumar, P. Ramamurthy, Unusual reactivity of 1-aminoanthraquinone in copper catalyzed multicomponent reaction with isatins and aryl alkynes: synthesis and photophysical properties of regioisomeric

S. Fery-Forgues, D. Lavabre, Are fluorescence quantum yields so tricky to measure? A

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[39]

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fluorescent 3-spiroheterocyclic 2-oxindoles,Tetrahedron, 69 (2013) 2891-2899.

C.F. Gers, J. Nordmann, C. Kumru, W. Frank, T.J.J. Müller, Solvatochromic fluorescent 2-substituted

3-ethynyl

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[40]

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demonstration using familiar stationery products, J. Chem. Educ., 76 (1999) 1260-1264.

quinoxalines:

four-component

synthesis,

photophysical

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[41]

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properties, and electronic structure, J. Org. Chem., 79 (2014) 3296-3310.

[42]

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(1999) 187-194.

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CC

the first excited singlet state, Z. Elektrochem. 61 (1957) 962–975

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[44]

K.N. Mataga, Y. Kaifu, M. Koizumi, Solvent effects upon fluorescence spectra and the dipole moments of excited molecules, Bull. Chem. Soc. Jpn., 29 (1956) 465-470. T. Anand, G. Sivaraman, D. Chellappa, Hg2+ mediated quinazoline ensemble for highly selective recognition of cysteine, Spectrochim. Acta Mol. Biomol.Spectrosc., 123 (2014) 18-24.

Author Biographies G. Harichandran is an Associate Professor in Department of Polymer Science, University of Madras, Chennai - 600 025, India. He received his Ph.D. degree from University of Madras in

SC RI PT

1997. He worked earlier in the School of Chemical Sciences, Mahatma Gandhi University, Kerala and University of Madras, Chennai, India. His current research interests include organic synthesis, corrosion prevention, pollution control and sensors.

P. Parameswari received her M. Sc., degree from the Department of Polymer Science,

U

University of Madras in 2012. She is presently working as Research Scholar in the Department

N

of Polymer Science, University of Madras and her research interests are organic synthesis and

M

A

sensors.

P. Shanmugam is a Senior Principal Scientist, Organic and Bio-organic Chemistry, CSIR-

D

Central Leather Research Institute (CLRI), Chennai, India. He received Ph.D. degree in

TE

Synthetic Organic Chemistry from University of Madras in 1997. His current research interests

A

CC

molecules.

EP

include organic synthesis and synthetic methods of functionalized heterocyclic and florescent

CC

EP

TE

D

M

A

N

U

Fig. 1. Bioactive benzophenazine and chromene molecules

SC RI PT

Figures, Schemes and Tables

A

Fig. 2. ORTEP diagram of the compounds 5g and 6e

SC RI PT

U

Fig. 3. Absorption (left panel) and normalized emission (right panel) spectra of Compounds 4H-

A

CC

EP

TE

D

M

A

N

Chromenes 5 (recorded at C = 1x10-4 M in chloroform at 298 K, λmax,exc = 420 nm).

Fig. 4. Absorption (left panel) and normalized emission (right panel) spectra of Compounds benzo[a]chromenophenazines 6 (recorded at C = 1x10-4 M in chloroform at 298 K, λmax,exc = 406 nm).

SC RI PT U N A M D TE EP CC

A

Fig. 5. Solvatochromism for the compounds 5a and 6a were recorded at C = 1x10-4 M at 298 K (absorption and emission spectra) [The insert in the right panel are the photographic images of the compounds in different solvents (1,4-Dioxane, CHCl3, DCM, CH3CN and DMF) under Visible (top) and UV light (bottom)].

SC RI PT A

N

U A

CC

EP

TE

D

M

Fig. 6. Lippert–Mataga plots for 5a and 6a

Fig. 7. Fluorescence spectra of compounds 5a and 6a (C = 1x10-4 M) in the presence of different metal ions (100µM) in CH3CN:H2O (9:1). Excitation was performed at 420 nm (5a) and 406 nm (6a).

SC RI PT U

CC

EP

TE

D

M

A

N

Fig. 8. Fluorescent emission spectra of 5a (C = 1x10-4 M) in the presence of different concentrations (0-200µM) of Fe3+ (left panel) and Cu2+ (right panel) in CH3CN:H2O (9:1). Excitation was performed for 5a at 420 nm. Inset: LOD determination

A

Fig. 9. Fluorescent emission spectra of 6a (C = 1x10-4 M) in the presence of different concentrations (0-200 µM) of Fe3+ (left panel) and Cu2+ (right panel) in CH3CN:H2O (9:1). Excitation was performed for 6a at 406 nm. Inset: LOD determination

SC RI PT

D

M

A

N

U

Scheme 1. General synthesis of 4H-chromenes 5 and benzo[a]chromenophenazines 6

A

CC

EP

TE

Scheme 2. Proposed mechanism for the formation of compound 5a

Scheme 3. Proposed mechanism for the formation of compounds 5a and 6a

Entry

Amberlite resin

Solvent

Time

Products/yield b (%)

(hr)

5a

6a

6

-

-

6

-

-

6

46

-

80

61

-

Temp (°C)

H2O

80

2

-

EtOH

80

3

IRA-400 Cl (150)

H2O

80

4

IRA-400 Cl (150)

EtOH

6

5

IRA-400 Cl (150)

EtOH/H2O

80

3

90

-

6

IRA-400 Cl (90)

EtOH/H2O

80

3

90

-

7

IRA-400 Cl (60)

EtOH/H2O

80

3

90

-

8

IRA-400 Cl (30)

EtOH/H2O

80

4

78

-

9

IRA-400 Cl (60)

EtOH/H2O

100

3

90

-

10

IRA-400 Cl (60)

EtOH/H2O

60

12

Trace

-

11

IRA-400 Cl (60)

EtOH/H2O

r.t

24

-

-

12

IR 120 (60)

EtOH/H2O

80

3

52

37

M

D

TE

EP

U

-

A

1

N

(mol%)

SC RI PT

Table 1. Optimization conditions for the synthesis of 5a/6aa

A

CC

The entry corresponding to optimal conditions is shown in bold. a 1.0 mmol of each reactant and the reaction was performed in EtOH/H2O (1/1, v/v) at 80 °C. b Isolated yield

A

CC

EP

TE

D

M

A

N

U

SC RI PT

Table 2. Synthesis of 4H-chromenes and benzo[a]chromenophenazines

Entry

Aldehyde

1,3-diketone

Products Yield (%)

(hr)

IRA-400 Cl resin

IR 120 H+ resin

3a

4a

3

5a (90)

5a (52)

6a (37)

2

3b

4a

4

5b (86)

5b (44)

6b (37)

3

3c

4a

4

5c (84)

4

3a

4b

3

5d (92)

5

3b

4b

4

5e (88)

6

3c

4b

4

5f (85)

7

3a

4c

4

5g (91)

8

3b

4c

4

5h (90)

9

3c

4c

4

5i (88)

10

3d

4a

4

5j (88)

11

3d

4b

4

5h (90)

12

3d

4c

4

N

A

M D TE EP CC A

U

1

SC RI PT

No

Time

5l (88)

5c (41)

6c (35)

5d (89)

-

5e (47)

6e (38)

5f (45)

6f (35)

5g (89)

-

5h (87)

-

5i (84)

-

5j (86)

-

5k (88)

-

5l (86)

-

Table 3. Selected absorption and emission data for the compounds 5 and 6

Entry

Compound λabs, [nm]a

Ɛ ×104 (L mol-1 cm-1) λem, [nm](Φf)a,b

Stokes shift

360, 402, 420

0.48, 0.69, 0.68

2

5b

360, 397, 418

0.53, 0.68, 0.71

3

5c

360, 402, 421

0.72, 0.96, 0.97

4

5d

361, 401, 420

0.44, 0.68, 0.69

5

5e

362, 399, 418

0.80, 1.11, 1.12

6

5f

361, 402, 420

0.62, 0.87, 0.89

7

5g

359, 397, 417

0.54, 0.70, 0.75

8

5h

360, 398, 418

0.51, 0.71, 0.67

9

5i

360, 402, 421

0.73, 0.91, 0.96

10

5j

360,401, 422

0.47, 0.56, 0.52

11

5k

360, 401, 421

12

5l

360, 397, 418

13

6a

14

6b

15

6c

16

6e

17

6f

b

466 (0.02)

2464

498 (<0.01)

3672

466 (0.07)

2237

462 (0.02)

2278

497 (<0.01)

3576

469 (0.02)

2601

492 (<0.01)

3655

475 (0.01)

2644

0.43, 0.53, 0.50

479 (0.02)

2876

0.90, 1.01, 0.96

462 (0.02)

2278

378, 404, 421

0.66, 0.82, 0.71

468 (0.01)

3323

379, 402, 420

0.47, 0.59, 0.53

460 (<0.01)

2070

378, 402, 419

0.63, 0.70, 0.75

450 (<0.01)

1644

379, 404, 421

0.41, 0.52, 0.44

450 (<0.01)

1530

0.88, 0.97, 0.86

452 (0.01)

1685

EP

TE

D

M

N

2794

378, 405, 420

Coumarin 153 as a standard in methanol Φf = 0.45

Stokes shift = 1/λmax,abs-1/λmax,emi [cm-1].

A

c

2578

472 (0.10)

Recorded at C = 1x10-4 M in chloroform at 298 K

CC

a

471 (0.03)

U

5a

A

1

SC RI PT

Δῡ (cm-1)c

Table 4. Absorption and emission data for the compounds 5a and 6a in different polarity of the solvents

Compound

Solvent

λabs, [nm]a

λem,[nm](Φf)a,b

Ɛ ×104

Δῡ (cm-1)c

0.49, 0.73, 0.73

Chloroform

360, 402, 420

0.48, 0.69, 0.68

DCM

359, 401, 421

0.50, 0.70, 0.70

Acetonitrile

358, 401, 416

0.64, 0.89, 0.88

DMF

363, 421

0.46, 0.68

1,4-Dioxane

407

0.91

Chloroform

404, 421

0.82, 0.71

DCM

405

0.92

Acetonitrile

407

0.77

DMF

410

Recorded at C = 1x10-4 M and at 298 K b Coumarin 153 as a standard in methanol Φf = 0.45 c Stokes shift = 1/λmax,abs-1/λmax,emi [cm-1].

A

CC

EP

TE

D

M

a

0.82

459 (0.02)

1966

471 (0.03)

2578

477 (0.02)

2788

480 (0.02)

3205

485 (0.04)

3190

462 (<0.01)

2925

N

U

359, 403, 422

A

6a

1,4-Dioxane

SC RI PT

(L mol-1 cm-1) 5a

Stokes shift

468 (0.01)

3323

471 (0.01)

3459

479 (<0.01)

3639

481 (0.02)

3600

Table 5. Fluorescence excitation spectral data of compounds 5a and 6a in the presence of different metal ions λem [nm]b

LOD

6a

5a

6a

5a

6a

8.4×10-5

-

-

482

479

3.2×10-6

Fe3+

482,532

482,532

3.7×10-6 , 4.1×10-6 1.1×10-6, 1.2×10-6 15 µM

15 µM d

Cu2+

482

485

3.6×10-6

1.0×10-6

20 µM

20 µM d

Pb2+

483

484

3.3×10-6

8.4×10-5

-

-

Co2+

483

485

3.2×10-6

8.0×10-5

-

-

Fe2+

483

485

3.2×10-6

8.4×10-5

-

-

Ni2+

483

485

3.2×10-6

8.2×10-5

-

-

Mn2+

482

486

3.1×10-6

8.2×10-5

-

-

Zn2+

482

485

3.3×10-6

8.6×10-5

-

-

Cd2+

482

486

3.2×10-6

8.3×10-5

-

-

Ag+

482

485

3.2×10-6

8.4×10-5

-

-

Hg2+

482

486

3.2×10-6

8.4×10-5

-

-

M

A

N

SC RI PT

-

U

Metal ionsa 5a

Fluorescence Intensity b, c

Recorded at 100 µM

b

Recorded at C = 1x10-4 M and at 298 K

c

Excitation was performed at 420 nm (5a) and 406 nm (6a).

d

Detectable metal ions as evidenced from LOD

A

CC

EP

TE

D

a