An efficient solvent free Amberlite IRA-400 Cl resin mediated multicomponent synthesis and photophysical properties of fluorescent 4H-chromene derivatives

Accepted Manuscript An efficient solvent free Amberlite IRA-400 Cl resin mediated multicomponent synthesis and photophysical properties of fluorescent 4H-chromene derivatives Gurusamy Harichandran, Parkunan Parameswari, Ponnusamy Shanmugam PII:

S0143-7208(16)30784-7

DOI:

10.1016/j.dyepig.2016.12.026

Reference:

DYPI 5651

To appear in:

Dyes and Pigments

Received Date: 21 September 2016 Revised Date:

19 November 2016

Accepted Date: 5 December 2016

Please cite this article as: Harichandran G, Parameswari P, Shanmugam P, An efficient solvent free Amberlite IRA-400 Cl resin mediated multicomponent synthesis and photophysical properties of fluorescent 4H-chromene derivatives, Dyes and Pigments (2017), doi: 10.1016/j.dyepig.2016.12.026. 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.

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An

efficient

solvent

free

Amberlite

IRA-400

Cl

resin

mediated

multicomponent synthesis and photophysical properties of fluorescent 4H-

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Gurusamy Harichandran,a* Parkunan Parameswari,a Ponnusamy Shanmugamb*

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chromene derivatives

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An

efficient

solvent

free

Amberlite

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multicomponent synthesis and photophysical properties of fluorescent 4H-

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chromene derivatives

4 5

IRA-400

Cl

resin

mediated

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Gurusamy Harichandran,a* Parkunan Parameswari,a and Ponnusamy Shanmugamb*

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a

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b

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600 020, India

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Department of Polymer Science, University of Madras, Guindy Campus, Chennai 600 025, India

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E-mail: [email protected]

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Abstract

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Organic and Bio-organic Chemistry Division, CSIR-Central Leather Research Institute (CLRI), Adyar, Chennai

An efficient Amberlite IRA-400 Cl basic anion exchange resin mediated multicomponent

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reaction of 2-hydroxybenzaldehydes, 1, 3-diketone and nucleophiles under neat condition

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afforded a number of fluorescent 4H-chromene derivatives in excellent yield. The structure of

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the synthesized compounds 4k and 4u were confirmed from single crystal XRD studies. 4H-

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Among the chromene derivatives, compound 4v synthesized from 4-diethylamino substituted 2-

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hydroxybenzaldehyde with dimedone and 2-hydroxynaphthaquinone has been found best

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florescent material. Photophysical properties such as solvatochromic effect, absorption,

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

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emission properties of the synthesized compounds suggested that these are a class of blue

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emissive fluorescent materials.

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Keywords

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Amberlite IRA-400 Cl resin; Multicomponent reactions; Solvent free condition; 4H-Chromenes;

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Photophysical properties

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Introduction Ecofriendly green organic syntheses evoke increasing interest in recent years resulted in

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the development of environmentally benign procedures such as solvent free synthesis,

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multicomponent reaction (MCR) and reusable heterogeneous catalyst to save resource materials

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and energy. These organic reactions possess advantages over conventional reactions. For

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example, solvent free MCR with reusable heterogeneous catalysts reduce the consumption of

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solvents and utilize scaled-down reaction vessels. MCRs are a simple and convergent atom-

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economic synthetic approach that offers advantages over conventional multi-step reaction for the

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synthesis of versatile array of molecular structures without isolation of intermediates thereby

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significantly reduces the wastage, time, and cost [1]. Moreover, the MCRs allow attaining the

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structurally diversified products by simply varying the substituent of different components.

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Hence, the MCR-based synthetic methodology is currently attractive in synthetic chemistry.

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

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of synthetic organic transformations [2-5]. The main advantage of Amberlite IRA-400 Cl resin

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catalyst is that it does not lead side reactions. Organic fluorescence materials are important due

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to their wide application from material science to organic electronics [6]. Among various

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fluorescence materials, substituted xanthenes have been found as fluorescence in nature [7].

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Moreover, xanthenes are also important class of heterocyclics widely distributed in many natural

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occurring compounds, used as Leuco dyes in laser technology, pH sensitive fluorescent materials

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[8] and also exhibit a wide spectrum of bioactivities [9-13]. Thus, among various synthetic

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studies, a few MCR’s have been developed for the synthesis of 3-substituted indoles [14] and

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chromenes [15-26]. Although chromenes have been synthesized by different methods, they

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suffer from use of harmful chemicals and solvents, extended reaction time, lower yields, and

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complex workup procedure. To the best of our knowledge, Amberlite IRA-400 Cl resin catalysed

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synthesis of 4H-chromene from 2-hydroxybenzaldehydes, active methylenes and carbon or

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nitrogen nucleophiles under solvent-free and resin catalytic condition and their photophysical

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properties has not been reported. Therefore, there is a need for efficient solid supported and eco-

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friendly protocol to obtain these valuable compounds. Thus, herein we report the one-pot

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multicomponent synthesis of functionalized 4H-chromene derivatives involving Knoevenagel-

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Michael-reaction catalyzed by Amberlite IRA-400 Cl basic anion exchange resin (Scheme 1).

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2.

Experimental

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2.1.

Materials and methods

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Scheme 1.

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Chemicals were procured from Spectrochem, SRL, Alfa Aesar, Sigma Aldrich and used

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as received. Melting points of all synthesized compounds were determined in open capillaries

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and are uncorrected. FT-IR spectra were recorded on a Thermo Mattson Satellite FT-IR

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spectrophotometer by KBr pellet method and 1H and

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Bruker ultra shield spectrometer (400 and 100 MHz) or Bruker ultra shield spectrometer (300

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and 75 MHz) in CDCl3 and or DMSO-d6 solvent using TMS as internal standard. Mass spectra

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were recorded on JEOL GCMATE II GC-MS Mass spectrometer. Chromatography purification

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was conducted using a column packed with silica gel and solvent mixture as specified. Solvents

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used for purification are of commercial grade and purified before used.

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C NMR spectra were recorded on a

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

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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 areas of the sample and the standard (quinine

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sulfate, Φf = 0.54 in 0.1M sulfuric acid), using the following equation. Qs = QR . Is/IR . ODR/ODs . ns2/n2R

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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 Quinine sulfate.

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2.2.

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General procedure for the preparation of 4H-chromene derivatives A mixture of 2-hydroxy benzaldehydes 1(a-c) (1.0 mmol), 1,3-dicarbonyl 2 (a-b) (1.0

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mmol), nucleophiles 3 (a-h) (1.0 mmol) and Amberlite IRA 400 Cl anion exchange resin (0.2 g)

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under solvent free condition was heated at 100 °C for 1 hour. After completion of the reaction (as

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indicated by TLC), the reaction mixture was cooled and diluted with ethyl acetate (10 mL) and

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the catalyst was removed by filtration. The filtrate was concentrated under reduced pressure and

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the crude mixture was purified by silica gel column chromatography using 1:4 mixture of ethyl

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acetate/petroleum ether (60-80 °C) as eluent to afford 4H-chromene products. The isolated

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compounds were characterized by FTIR,

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crystallographic study.

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C NMR, HRMS and an X-ray

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2.3. Spectroscopic characterization of the new compounds

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9-(5-Bromo-1H-indol-3-yl)-3,3-dimethyl-7-bromo-2,3,4,9-tetrahydro-1H-xanthen-1-one (4q)

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White crystalline solid (yield 86%); mp 202 °C; Rf 0.72 (EtOAc:Petroleum ether, 2:3);

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FT-IR (KBr) νmax: 3333, 2951, 2883, 1735, 1636, 1573, 1473, 1378, 1229, 1174, 1070, 1028,

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797, 751 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 0.96 (3H, s, CH3), 1.10 (3H, s, CH3),

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2.22 (2H, d, J = 18.8 Hz, CH2), 2.57 (2H, d, J = 8.4 Hz, CH2), 5.18 (1H, s, CH), 6.97-7.11 (4H,

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m, ArH), 7.21-7.25 (2H, m, ArH), 7.45 (1H, s, ArH), 8.57 (1H, brs, NH); 13C NMR (100 MHz,

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CDCl3): δC (ppm) 27.33, 29.17, 29.54, 32.08, 41.46, 50.91, 112.04, 112.76, 112.95, 117.43,

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118.29, 119.32, 121.37, 123.90, 124.57, 126.94, 127.15, 130.76, 132.77, 135.25, 148.47, 164.49,

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197.51; HRMS m/z (ESI) Calcd. for C23H19Br2NO2 [M]+ 501.2105; Found 501.2100.

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9-(2-Methyl-1H-indol-3-yl)-3,3-dimethyl-7-bromo2,3,4,9-tetrahydro-1H-xanthen-1-one (4r)

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White crystalline solid (yield 90%); mp 248 °C; Rf 0.76 (EtOAc:Petroleum ether, 2:3);

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FT-IR (KBr) νmax: 3331,2957, 1640, 1574, 1473, 1377, 1226, 1175, 1071, 1027, 762, 738 cm−1;

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16 Hz), 2.24 (1H, d, J = 16.4 Hz ), 2.52 (1H, d, J = 4.8 Hz), 2.56 (3H, s, CH3), 2.63 (1H, d, J =

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17.6 Hz), 5.13 (1H, s, CH), 6.78 (1H, t, J = 7.4 Hz, ArH), 6.89 (1H, t, J = 7.4 Hz, ArH ), 7.05

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(1H, d, J = 7.2 Hz, ArH), 7.13-7.19 (3H, m, ArH), 7.33 (1H, d, J = 8.4 Hz, ArH), 10.80 (1H, brs,

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NH);

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111.13, 111.85, 114.87, 116.69, 117.25, 118.79, 120.24, 126.65, 128.30, 130.80, 132.43, 132.73,

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135.52, 148.79, 163.73, 196.52; HRMS m/z (ESI) Calcd. for C24 H22BrNO2 [M]+ 436.3410;

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Found 436.3408.

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C NMR (100 MHz, DMSO-d6): δC (ppm) 12.00, 26.91, 28.19, 29.24, 32.02, 50.63,

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H NMR (400 MHz, DMSO-d6): δH (ppm) 0.81 (3H, s, CH3), 1.03 (3H, s, CH3), 2.02 (1H, d, J =

9-(1H-indol-3-yl)-3,3-dimethyl-6-(diethylamino)-2,3,4,9-tetrahydro-2H-xanthen-1-one (4u) White crystalline solid (yield 88%); mp 164 °C; Rf 0.73 (EtOAc:Petroleum ether, 2:3);

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λmax, abs = 249, 306, 370 nm; λmax, emi = 410, 434, 461 nm (in DCM); FT-IR (KBr) νmax: 3343,

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2962, 2863, 1738, 1634, 1557, 1516, 1469, 1374, 1229, 1101, 1038, 779, 735 cm−1; 1H NMR

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(300 MHz, CDCl3): δH (ppm) 0.95 (3H, s, CH3), 1.09-1.14 (9H, m, (CH3)3), 2.20 (2H, d, J = 6.3

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Hz, CH2), 2.54 (2H, d, J = 6.6 Hz, CH2 ), 3.29 (4H, d, J = 6.9 Hz), 5.19 (1H, s, CH), 6.34 (2H,

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d, J= 8.1 Hz, ArH ), 6.95 (2H, d, J = 5.7 Hz, ArH ), 7.03-7.11 (2H, m, ArH), 7.24 (1H, d, J = 7.8

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Hz, ArH), 7.42 (1H, d, J = 7.5 Hz, ArH), 8.03 (1H, brs, NH);

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(ppm) 12.56, 27.78, 28.67, 29.01, 32.06, 41.74, 44.41, 51.01, 98.65, 109.38, 111.10, 111.98,

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113.29, 119.37, 121.14, 121.38, 122.20, 125.91, 130.40, 136.61, 147.46, 150.48, 164.44, 197.47;

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HRMS m/z (ESI) Calcd. for C27H30N2O2 [M]+ 414.5393; Found 414.5390.

C NMR (75 MHz, CDCl3): δC

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2-(6-diethylamino)-2,3,4,9-tetrahydro-3,3-dimethyl-1-oxo-1H-xanthen-9-yl)-3-hydroxynaphtha

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lene-1,4-dione (4v)

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Orange solid (yield 82%); mp 190 °C; Rf 0.75 (EtOAc:Petroleum ether, 2:3); λmax, abs =

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270, 307, 394 nm; λmax, emi = 405, 430, 456 nm (in DCM); FT-IR (KBr) νmax: 3229, 2962, 2923,

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1675, 1644, 1562, 1515, 1462, 1367, 1273, 1226, 1102, 1039, 765, 728 cm−1; 1H NMR (400

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MHz, CDCl3): δH (ppm) 1.05 (3H, s, CH3), 1.11-1.15 (10H, m, (C2H5)2), 1.21 (3H, s, CH3), 2.18-

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2.31 (2H, m, CH2), 2.52-2.58 (2H, m, CH2), 5.35 (1H, s, CH), 6.33 (2H, d, J = 8.0Hz, ArH ),

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6.92 (1H, d, J = 8.4Hz, ArH ), 7.59-7.69 (3H, m, ArH), 7.99-8.00 (1H, s, ArH), 8.08 (1H, brs,

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OH);

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41.79, 44.35, 50.74, 53.10, 98.69, 108.75, 108.94, 110.62, 118.72, 118.84, 120.65, 125.85,

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126.11, 126.96, 129.51, 132.69, 132.78, 134.76, 147.91, 148.53, 150.82, 152.42, 166.84, 167.22,

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182.11, 183.87, 192.12, 197.12, 197.47; HRMS m/z (ESI) Calcd. for C29H29NO5 [M]+ 471.5443;

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Found 471.5441.

C NMR (100 MHz, CDCl3): δC (ppm) 12.57, 27.41, 28.69, 29.26, 32.12, 36.33, 38.24,

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3. Results and discussion Initially, to synthesis 9-(1H-indol-3-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-

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one 4a and to optimize the three component reaction conditions, 2-hydroxybenzaldehyde 1a,

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dimedone 2a and indole 3a were chosen as model substrates. Thus, a 1:1:1 mixture of 1a, 2a and

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3a without any catalyst and solvent was heated at 100 °C for 1h. The reaction afforded isolable

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mixture of compounds 4a, 4h and 5a in 8 %, 22 % and 26 % yields, respectively and the

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structure of the compounds were established by spectroscopic data (Table 1, entry 1). Since

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various products 4a, 4h and 5a observed in the above reaction due to competitive nucleophilic

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reactions, we envisaged to study the competitive reactivity of nucleophiles 2a and 3a in the

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reaction by change of mole ratio of these reactants. Thus, increasing the mole ratio of one of

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nucleophiles predominantly took part in the reaction to afford compounds 4a (4-8 %), 4h (18-38

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%) and 5a (30-41%) and the results are shown in table 1, entries 2-5. In order to obtain sole

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product 4a and to optimizing the role and effect of the catalyst Amberlite IRA-400 Cl resin in the

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reaction, a reaction of 1:1:1 mixture of 1a, 2a and 3a with 0.3 mmol of Amberlite IRA-400 Cl

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resin catalyst under neat condition was heated at 100 °C for 1h (Table 1, entry 6). The result

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revealed that the each reactant equally take part in the reaction and afforded a single product 4a

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in 75 % yield with a trace of non-isolable products 4h and 5a (as indicated in TLC only). To

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evaluate the appropriate catalyst loading, the reaction was carried out using different amount of

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catalyst (Table 1, entries 6-8). It was found that 200 mg (0.6 mmol) was the most effective

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catalyst loading, the product 4a yield was substantially increased to 90 % (Table 3, entry 7) and

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increase in catalyst amount did not improved the yield. The reaction temperature also plays a

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crucial role in the product yield. Altering the reaction temperature to 80 ºC or 100 ºC, the yield of

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product 4a found to be decreased (Table 1, entries 7-10). However, when the reaction is carried

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out under similar conditions by using Amberlite IR-120 (H+) resin (200 mg) afforded the product

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4a in good yield (Table 1, entry 11). Considering the above results, the model MCR can be most

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efficiently catalyzed by Amberlite IRA-400 Cl resin (200 mg) under solvent free condition at

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100 °C for 1 h (Table 1, entry 7) and found to be optimized condition.

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Table 1.

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Encouraged by the preliminary results and to demonstrate the method as general, under

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optimized condition, a number of nucleophiles 3(a–h) (1.0 mmol) were reacted with

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2-hydroxybenzaldehydes 1(a-c) (1.0 mmol) and 1, 3-dicarbonyl compounds (2a or 2b). All the

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reactions underwent smoothly and provided the desired compounds (4a–4v) in excellent yields

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(80-93%) with the trace amount of byproducts and the results are summarized in Table 2.

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Table 2.

As the results shown in table 2, it has been observed that both electron donating and

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withdrawing substituents in indole nucleophiles such as 5-bromo-indole 3b, 2-methyl-indole 3c

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did not altered the yields significantly (Table 2, entries 2, 3). Best yield (92%) was obtained

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while using 2-methyl-indole 3c as a nucleophile (Table 2, entry 3). Similarly, nucleophiles 2-

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naphthol 3e, 4-hydroxycoumarin 3f, 2-hydroxy-1,4-naphthaquinone 3g and barbituric acid 3h

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afforded respective products 4d, 4e, 4f and 4g

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Similarly, reaction of 1:2 ratio of aldehyde 1a with dimedone 2a or 1,3-cyclohexanedione 2b

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(1 equiv to act as nucleophile) afforded corresponding compounds 4h (93%) and 4o (91%) in

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excellent yields (Table 2 entries 8, 15). Significantly, as expected the reactions between 1a, 2b

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in excellent yields (Table 2, entries 4-7).

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and 3a-f afforded respective 4H-chromene derivatives (4i–m) in good yields (Table 2, entries 9–

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14). Similarly, the MCR between 1b, 2a and 3a-f afforded 4H-chromenes (4p-t) in good yields

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(Table 2, entries 16-20). Furthermore, the reaction of 1c, 2a and 3a or 3g, the expected 4H-

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chromenes (4u and 4v) was obtained in good yields (Table 2, entries 21-22). All the new

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compounds were characterized by spectroscopic data (IR, 1H NMR, 13C NMR and HRMS). Final

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structure proof of representative compounds 4k and 4u was obtained from single crystal X-ray

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studies [27] (Fig. 1).

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Fig. 1.

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Plausible mechanisms for the formation of compounds 4a, 4h and 5a without the use of

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Amberlite resin catalyst is outlined in Scheme 2. In the initial step, it is believed that in the

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absence of catalyst, the Knoevenagel condensation reaction between 2-hydroxybenzaldehyde 1

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and dimedone 2 forms intermediate I. Subsequently, two competitive Michael type additions are

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possible for intermediate I as shown in pathways A and B. Pathway-A explains the Michael

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addition of indole 3a to intermediate I followed by dehydration paving the way to its ring closure

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to afford the 4H-chromene product 4a. As shown in Pathway-B, the proton of the enolic hydroxy

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group in the dimedone is more reactive nucleophile than that of indole, the Michael addition of

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enolic hydroxy group of the dimedone easily reacts with the intermediate I followed by

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dehydration to afford the 4H-chromene product 4h. Therefore, dimedone has the priority

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compared to indole to act as a second nucleophile, which ensures the high selectivity of the

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reaction under solvent and catalyst free condition. The third bis(indolyl)methane 5a product

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formation is explained in pathway-C. The reaction between indole 3a and 2-hydroxy

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benzaldehyde 1a to form intermediate adduct II with the liberation of water. Subsequently

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another indole 3a reacts with the adduct II to form a bis(indolyl)methane 5a [28].

Scheme 2.

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A plausible mechanism for the selective formation of compounds 4a, in the presence of

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the resin catalyst is outlined in Scheme 3. Initially, it is believed that the Amberlite resin

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catalyzes the Knoevenagel condensation reaction between 2-hydroxybenzaldehyde 1 and active

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methylene compound 2 to afford intermediate I. In the key second step, Amberlite resin catalyst

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controlled Michael addition of indole 3a to intermediate I followed by dehydration to afford the

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4H-chromene product 4a as a sole product.

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Scheme 3.

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Photophysical studies

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The structure and physical nature of the synthesized compounds prompted us to explore

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their photophysical properties. Hence, based on absorption and structure uniqueness, selective

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compounds were evaluated for photophysical characteristics such as absorption (λmax), emission

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(λem), quantum yield (ɸf) and Stokes shift (∆ῡ) [29, 30]. Thus, the photophysical data collected

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are presented in Table 3. Figure 2 shows normalized absorption and emission spectra of

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compounds 4e, 4f, 4l, 4u and 4v. The absorption maxima of 4H-chromenes are found to be in a

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broad range from 252 to 394 nm. These compounds have also showed bright fluorescence in

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dichloromethane solvent. It has been observed that the fluorescence spectra exhibited similar

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emission pattern for compounds 4e, 4f, 4l, 4u and 4v in the range of 405 to 462 nm. Stokes shifts

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and quantum yields of 4H-chromenes were calculated using dichloromethane as solvent.

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Significantly, among the compounds 4e, 4f, 4l, 4u and 4v, compounds 4u and 4v showed lesser

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Stokes shifts and higher quantum yield, and the results showed in Table 3.

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Fig. 2.

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Table 3.

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To demonstrate the influence of solvents [31] on the emission properties of 4H-

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chromenes 4e, 4f, 4l, 4u and 4v, the fluorescence spectra were recorded in different polarity of

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solvents i.e chloroform, dichloromethane, 1,4-dioxane, tetrahydrofuran and methanol. The 4H-

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chromenes 4e, 4f and 4l exhibit similar emission pattern ranging from 406 to 462 nm in

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dichloromethane and chloroform, whereas in tetrahydrofuran, 1,4-dioxane and methanol the

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peaks were observed at lower emission wavelength ranging from 385 to 432 nm and the

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corresponding photographic images of fluorescent solutions were inserted in Fig. 3(a-c). In

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contrast to the above observation, compounds 4u and 4v exhibits different emission in

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dichloromethane and tetrahydrofuran where the emission peak observed in the lower wavelength.

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However, solvents in chloroform, 1,4-dioxane and methanol, the emission peak shifted to red

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shift region as shown in Fig. 3(d and e). This might be due to presence of electron donating

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substituent i.e., N,N-diethyl amino group extends the conjugation in the 4H-chromene

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derivatives. From the data presented in table 4, it is clear that the Stokes shift is more in non-

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polar solvents for 4H-chromene without donor group. Similarly, the Stokes shift is more in polar

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solvents for 4H-chromene with donor group. The presence of donor group makes the molecule as

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more polar in the excited state as evidenced from larger Stokes shift and larger wavelength

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emission. Optical properties such as absorption, excitation, emission and Stokes shifts of 4H-

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chromene derivatives are summarized in table 4.

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Fig. 3.

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Table 4.

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4. Conclusions

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In summary, we have demonstrated a facile and efficient Knoevenagel condensation and

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Michael addition reaction for the synthesis of 4H-chromenes. A plausible mechanism for the

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formation of all the products with and without Amberlite resin catalyst has been provided.

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Photophysical properties such as solvatochromic effect, absorption, emission, Stocks shift and

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quantum yield of the selected compounds have been evaluated and the emission properties

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suggesting that these are a class of blue emissive fluorescent materials. Further work using

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Amberlite IRA-400 Cl catalyst in organic synthesis is under investigation in this laboratory.

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Acknowledgments

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One of the authors, P. P. acknowledges University of Madras for providing fellowship

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under UPE (II) – New Materials project. G.H. thanks the University of Madras for providing

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

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single crystal measurements, respectively.

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References

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[1]

Zhu J, Wang Q, Wang M. Multicomponent Reactions in Organic Synthesis, John Wiley & Sons 2014.

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[2]

Akelah A, Sherrington DC. Chem Rev 1981; 81: 557-87.

5

[3]

Khodaei MM, Bahrami K, Farrokhi A. Synth Commun 2010; 40: 1492-9.

6

[4]

Chaturvedi D, Mishra N, Mishra V. J Sulfur Chem 2007; 28: 607-12.

7

[5]

Harichandran G, David Amalraj S, Shanmugam P. J Heterocycl Chem 2013; 50: 539-43.

8

[6]

Müller TJJ. In Functional Organic Materials: Syntheses, Strategies and Applications;

SC

M AN U

Wiley-VCH: Weinheim, Germany, 2007; 179-223.

9

RI PT

4

10

[7]

Bhowmik BB, Ganguly P. Spectrochim Acta A 2005; 61: 1997-2003

11

[8]

Sarma RJ, Baruah JB. Dyes Pigments 2005; 64: 91-2.

12

[9]

Zonouzia A, Mirzazadeha R, Safavi M, Ardestanic SK, Emamid SA, Foroumadi. Iran J

[10]

2007; 17: 6459-62. [11]

Kidwai M, Saxena S, Khanb MKR, Thukral SS. Bioorg Med Chem Lett 2005; 15: 42958.

17 18

[12]

19

[13]

EP

15 16

Kumar RR, Perumal S, Senthilkumar P, Yogeeswari P, Sriram D. Bioorg Med Chem Lett

Wen L, Zhang H, Lin H, Shen Q, Lu L. J Fluorine Chem 2012; 133: 171-7.

AC C

14

TE D

Pharm Res 2013; 12: 679-86.

13

Mahmoodi M, Aliabadi A, Emami S, Safavi M, Rajabalian S, Mohagheghi MA, Khoshzaban A, Kermani AS, Lamei N, Shafiee A, Foroumadi A. Arch Pharm Chem Life

20

Sci 2010; 343: 411-6.

21 22

[14]

Ravindran A, Kore R, Srivastava R. Indian J Chem 2013; 52B: 129-35.

23

[15]

Peng Z, Yong-Dong Y, Zhan-Hui Z. Synth Commun 2008; 38: 4474-9.

13

ACCEPTED MANUSCRIPT

1

[16]

Kuarm BS, Madhav JV, Reddy YT, Laxmi SV, Reddy PN, Rajitha B, Crooks PA. Synth Commun 2011; 41: 1719-24.

2

[17]

Li M, Zhanga B, Gu Y. Green Chem 2012; 14: 2421-8.

4

[18]

Ganguly NC, Roy S, Mondal P, Saha R. Tetrahedron Lett 2012; 53: 7067-71.

5

[19]

Minghao L, Yanlong G. Adv Synth Catal 2012; 354: 2484-94.

6

[20]

Ghosh PP, Das AR. J Org Chem 2013; 78: 6170-81.

7

[21]

Khalafi-Nezhad A, Nourisefat M, Panahi F. Synthesis 2014; 46: 2071-8.

8

[22]

Mandlimath TR, Umamahesh B, Sathiyanarayanan KI. J Mol Catal A Chem 2014; 391:

SC

M AN U

198-207.

9

RI PT

3

10

[23]

Najmedin Azizi, Mahboobe Mariami, Mahtab Edrisi, Dyes Pigments 2014; 100: 215-21.

11

[24]

Harichandran G, Parameswari P, Kanagaraj M, Shanmugam P. Tetrahedron Lett 2015; 56: 150-4.

12

[25]

Kasralikar HM, Jadhavar SC, Bhusare SR. Bioorg Med Chem Lett 2015; 25: 3882–6

14

[26]

Kasralikar HM, Jadhavar SC, Bhusare SR. Synlett 2015; 26: 1969-72

15

[27]

CCDC 1404258 [4k] and CCDC 1465275 [4u] contain the supplementary

TE D

13

crystallographic data. These data can be obtained free of charge from The Cambridge

17

Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. [28]

19

[29]

[30]

Denißen M, Nordmann J, Dziambor J, Mayer B, Frank W, Müller TJJ. RSC Adv 2015, 5: 33838–54.

22 23

Periyaraja S, Shanmugam P, Mandal AB, Senthil Kumar T, Ramamurthy P. Tetrahedron 2013; 69: 2891-9.

20 21

Dhumaskar KL, Tilve SG. Green Chemistry Letters and Reviews 2012; 5: 353-402

AC C

18

EP

16

[31]

Gers CF, Nordmann J, Kumru C, Frank W, Müller TJJ. J Org Chem 2014; 79: 3296-310.

14

ACCEPTED MANUSCRIPT

Captions

2

Scheme 1 Synthesis of functionalized 4H-chromenes

3

Table 1 Optimization conditions for the synthesis of 4aa

4

Table 2 Synthesis of functionalized 4H-chromenes by using Amberlite IRA-400 Cl resin as

5

catalyst

6

Fig. 1 ORTEP diagrams of the compounds 4k and 4u

7

Scheme 2 Plausible mechanism for the formation of compound 4a, 4h and 5a without catalyst

8

Scheme 3 Plausible mechanism for the formation of compound 4a in the presence of IRA-400 Cl

9

resin catalyst

M AN U

SC

RI PT

1

Fig. 2 Normalized absorption and emission spectra of selective 4H-chromenes in

11

dichloromethane

12

Table 3 Absorption, emission, fluorescence quantum yields and Stokes shifts of 4H-chromenes 4

13

(recorded in dichloromethane, T = 298 K)

14

Fig. 3 Solvatochromism of 4H-chromenes 4e(a), 4f(b), 4l(c), 4u(d) and 4v(e) [Emission]. The

15

insert images shows compounds in different solvents (DCM, THF, CHCl3, 1,4-Dioxane, MeOH

16

respectively) under Vis (top) and UV (bottom) light.

17

Table 4 Absorption, excitation, emission and Stokes shifts of 4H-chromenes 4 (recorded in a

18

different solvents at T = 298 K)

20 21

EP

AC C

19

TE D

10

22 23 24 15

ACCEPTED MANUSCRIPT

Scheme 1.

3 4

Nu

O

2

CHO

IRA-400 Cl

R

NuH OH O 2(a-b)

1(a-c)

solvent free,100 oC

4(a-v)

6

SC

7 8

M AN U

9 10 11 12

18 19 20 21

EP

17

AC C

16

TE D

13

15

O

R 3(a-h)

5

14

O

RI PT

1

22 23 24 25

16

ACCEPTED MANUSCRIPT

1

Table 1 .

2 NH

O CHO + OH O

4

N H

1a

solvent free,100 C

5

Entry

11 12

OH +

O

O

4a

4h

N H

N H

5a

Reactants

Amberlite IRA

Temp

Time

Products

(equivalent)

400 Cl resin

(°C)

(h)

Yieldc (%)

1a

2a

3a

mg (mmol)

1

1

1

1

-

100

2

1

0.5

1

-

100

3

1

1

0.5

-

100

4

1

2

1

-

5

1

1

2

6

1

1

7

1

8

4h

5a

1

8

22

26

1

4

18

30

1

5

31

20

100

1

8

38

28

-

100

1

8

23

41

1

100 (0.3)

100

1

75

-

-

1

1

200 (0.6)

100

1

90

-

-

1

1

1

300 (0.9)

100

1

90

-

-

9

1

1

1

200 (0.6)

120

1

72

-

-

10

1

1

1

200 (0.6)

80

1

44

-

-

11

1

1

1

200b (0.6)

100

1

73

-

-

TE D

M AN U

SC

4a

EP

The significance of bold values indicates the optimized condition. a 1.0 mmol of each reactants and reaction was performed under solvent free condition at 100 °C. b Amberlite IR 120 resin was used, mmol of H+ resin. c Isolated yield.

AC C

6 7 8 9 10

OH O

+

o

3a

2a

O

O

IRA-400 Cl +

RI PT

3

13 14 15

17

ACCEPTED MANUSCRIPT

Table 2. O CHO

Br

CHO

OH

Et

N Et

1b

1a

O

CHO

OH

O

OH

O

1c

2b

2a OH

N H

N

3c

3b

NH O

O

O O

O 4h

O 4g

O

EP

NH

OH O

O

NH

Br

O

O

O 4j

O

O O

O O

O 4o

O OH O

O Br

Br

O 4u

O 4s O HO

O

Et

N

Et

44 45 18

O O

O 4v

HO

O O

Br

O 4r

NH

N Et

O 4e

O 4n

O

O 4q

Et

O O

NH

Br

O 4p

HO

O 4m

NH

Br

O

HO

O

O

O 4l

O 4k

3h

O 4i

N

NH

Br

OH O

TE D

O 4f

O

NH

NH

O

NH

N H

O 4d

M AN U

O O

3g

OH O

O 4c

O HN

O

NH O

O 4b

O

O

3f

O

O 4a

O

3e

3d

NH

Br

HO

O

SC

3a

N H

OH

RI PT

OH

N H

O

O

Br

AC C

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43

O 4t

ACCEPTED MANUSCRIPT

Melting point (°C) Found

Reported

2a

3a

1.0

4a

90

117

117-119 [20]

2

1a

2a

3b

1.0

4b

88

206

205-208 [21]

3

1a

2a

3c

1.0

4c

92

213

212-214 [19]

4

1a

2a

3e

1.0

4d

88

232

234-236 [20]

5

1a

2a

3f

1.5

4e

87

226

225-227 [17]

6

1a

2a

3g

1.5

4f

88

255

254-256 [17]

7

1a

2a

3h

1.5

4g

86

153

150-152 [17]

8

1a

2a

2a

1.0

4h

93

209

209-211 [17]

9

1a

2b

3a

1.0

4i

88

257

255-258 [21]

10

1a

2b

3b

1.0

4j

86

246

244-247 [21]

11

1a

2b

3c

1.0

4k

90

238

237-240 [21]

12

1a

2b

3d

1.0

4l

81

214

212-215 [21]

13

1a

2b

3e

1.5

4m

83

212

211-213 [20]

14

1a

2b

3f

1.5

4n

80

206

207-209 [20]

15

1a

2b

2b

1.0

4o

92

227

230 [22]

16

1b

2a

3a

1.0

4p

89

223

225 [25]

17

1b

2a

3b

1.0

4q

86

202

This work

18

1b

2a

3c

1.0

4r

90

248

This work

19

1b

20

1b

21

1c

1c

M AN U

TE D

EP

RI PT

1a

2a

3e

1.5

4s

82

264

262-264 [21]

2a

3f

1.5

4t

80

242

241 [25]

2a

3a

1.5

4u

88

164

This work

2a

3g

1.5

4v

82

190

This work

AC C

2

Yield (%)

1

22 1

1,3 NuH Time Product(s) diketones (h)

SC

Entry Aldehydes

3 4 5 19

ACCEPTED MANUSCRIPT

1

Fig. 1.

2 3

RI PT

4 5 6

SC

7 8

M AN U

9 10 11 12

16 17 18 19 20

EP

15

AC C

14

TE D

13

21 22 23

20

ACCEPTED MANUSCRIPT

1

Scheme 2.

2 3

5

Pa th

A

RI PT

th Pa

4

B

6

SC

7 8

M AN U

9 10 11 12

14

TE D

13

Scheme 3.

resin

15

O

HC

16

O HO

EP

O

1a

resin

17

O

O

O

resin

O

O

-H 2O

H

OH

O

N H

OH

2a

AC C

18

resi n

H

O

I

resin = IRA-400 Cl

19 20

NH NH

NH O

O H

O

-H 2O

21 O

22

O

4a

23

21

OH

OH

3

ACCEPTED MANUSCRIPT

1

Fig. 2.

SC M AN U TE D EP AC C

3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39

RI PT

2

22

ACCEPTED MANUSCRIPT

Table 3. Excitation

Emission

Quantum

Stokes shift

λmax, [nm]

λmax, [nm]

λmax, [nm]

yield (ɸf)b

∆ῡ (cm-1)c

4e

272, 282, 310, 341 sh

355

409, 435, 460

4f

252, 277, 340 sh

355

410, 435, 460

4l

276, 338 sh

355

410, 435, 462

4u

249, 306, 370 sh

370

410, 434, 461

4v

270, 307, 394 sh

370

405, 430, 456

a

7

12 13 14 15 16

EP

11

AC C

10

TE D

8 9

0.06

6337

0.03

6423

0.09

6597

0.11

3986

0.19

2125

Recorded at c=10-4 M (in the absorption maxima sh stands for shoulder) b Determined in 0.1M sulfuric acid with quinine sulfate as a standard (ɸf = 0.54) c Stokes shift = λmax,abs-λmax,emi [cm-1].

M AN U

3 4 5 6

RI PT

Absorptiona

Compound

SC

1 2

17 18 19 23

ACCEPTED MANUSCRIPT

1

Fig. 3.

2 3

RI PT

4 5 6

SC

7 8

M AN U

9 10 11 12

16 17 18 19 20

EP

15

AC C

14

TE D

13

21 22 23

24

ACCEPTED MANUSCRIPT

Table 4. Compound

Solvent

4e

DCM THF CHCl3 1,4-Dioxane MeOH

Absorptiona λmax, [nm] 272, 282, 310, 341 271, 282, 310, 343 272, 283, 310, 341 310, 341 310, 339

4f

DCM THF CHCl3 1,4-Dioxane MeOH

252, 276, 340 253, 276, 336 252, 279, 338 251, 279, 344 274, 340

355 355 355 355 355

4l

DCM THF CHCl3 1,4-Dioxane MeOH

276, 338 292, 338 252, 276, 338 285, 336 279, 338

4u

DCM THF CHCl3 1,4-Dioxane MeOH

249, 306, 370 249, 293, 374 249, 293, 374 276, 285, 371 250, 308, 374

410, 435, 460 399, 426 408, 433, 458 385, 400 398, 422

6423 4699 6491 3096 4287

355 355 355 355 355

410, 435, 462 415, 430 406, 432, 460 407 399, 421

6597 6330 6438 5192 5832

370 370 370 370 370

410, 434, 461 400, 429, 454 475 475 510

3986 3428 5685 5902 7130

370 370 370 370 370

405, 430, 456 403, 428, 455 401, 425, 500 523 490, 555

2125 3091 4842 4842 9380

355 355 355 355 355

RI PT

409, 435, 460 398, 432 407, 432, 458 385, 400 398, 421

Stokes shift ∆ῡ (cm-1)c 6337 4049 6177 3351 4373

SC

DCM 270, 307, 394 THF 287, 320, 378 CHCl3 287, 303, 388 4v 1,4-Dioxane 308, 356, 409 MeOH 257, 272, 365 a,b -4 Recorded at c=10 M c Stokes shift = λmax,abs-λmax,emi [cm-1].

AC C

2 3 4

Excitation Emissionb λmax, [nm] λmax, [nm]

M AN U

TE D

EP

1

5 6 7 25

ACCEPTED MANUSCRIPT

Supplementary data

1

An

efficient

solvent

free

Amberlite

IRA-400

3

multicomponent synthesis and photophysical properties of fluorescent 4H-

4

chromene derivatives

5 6

Gurusamy Harichandran,a* Parkunan Parameswari,a Ponnusamy Shanmugamb*

resin

mediated

SC

7

Cl

RI PT

2

a

Department of Polymer Science, University of Madras, Guindy Campus, Chennai 600 025, India

9

b

Organic Chemistry Division, CSIR-Central Leather Research Institute (CLRI), Adyar, Chennai 600 020, India

10

E-mail: [email protected]

11

2.

Experimental

13

2.1.

Materials and methods

TE D

12

M AN U

8

Chemicals were procured from Spectrochem, SRL, Alfa Aesar, Sigma Aldrich and used

15

as received. Melting points of all synthesized compounds were determined in open capillaries

16

and are uncorrected. FT-IR spectra were recorded on a Thermo Mattson Satellite FT-IR

17

spectrophotometer by KBr pellet method and 1H and

18

Bruker ultra shield spectrometer (400 and 100 MHz) or Bruker ultra shield spectrometer (300

19

and 75 MHz) in CDCl3 and or DMSO-d6 solvent using TMS as internal standard. Mass spectra

20

were recorded on JEOL GCMATE II GC-MS Mass spectrometer. Chromatography purification

21

was conducted using a column packed with silica gel and solvent mixture as specified. Solvents

22

used for purification are of commercial grade and purified before used.

13

C NMR spectra were recorded on a

AC C

EP

14

23

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

24

range of 200−1100 nm. Steady-state fluorescence spectra were recorded using Fluoromax 4 26

ACCEPTED MANUSCRIPT

1

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

2

yields (Φf) were obtained by comparing corrected areas of the sample and the standard (quinine

3

sulfate, Φf = 0.54 in 0.1M sulfuric acid), using the following equation. Qs = QR . Is/IR . ODR/ODs . ns2/n2R

5

Where Q is the quantum yield, I is the integrated intensity, OD is the optical density, and n is the

6

refractive index. The subscript R refers Quinine sulfate.

8

2.2.

SC

7

RI PT

4

General procedure for the preparation of 4H-chromene derivatives A mixture of 2-hydroxy benzaldehydes 1(a-c) (1.0 mmol), 1,3-dicarbonyl 2 (a-b) (1.0

10

mmol), nucleophiles 3 (a-h) (1.0 mmol) and Amberlite IRA 400 Cl anion exchange resin (0.2 g)

11

under solvent free condition was heated at 100 °C for 1 hour. After completion of the reaction

12

(as indicated by TLC), the reaction mixture was cooled and diluted with ethyl acetate (10 mL)

13

and the catalyst was removed by filtration. The filtrate was concentrated under reduced pressure

14

and the crude mixture was purified by silica gel column chromatography using 1:4 mixture of

15

ethyl acetate/petroleum ether (60-80 °C) as eluent to afford pure products. The isolated

16

compounds were characterized by FTIR,

17

crystallographic study.

19 20 21

TE D

H NMR,

EP

1

AC C

18

M AN U

9

22 23 24

27

13

C NMR, HRMS and an X-ray

ACCEPTED MANUSCRIPT

1. Spectroscopic data of compounds White crystalline solid (yield 90%); mp117 °C; Rf 0.74 (EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3411,

NH O

RI PT

3332, 3056, 2956, 2929, 2872, 1639, 1580, 1486, 1454, 1421, 1374, 1226, 1178, 1144, 1098, 1012, 757 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 0.96 (3H, s, CH3), O 4a

1.10 (3H, s, CH3), 2.16-2.27 (2H, m, CH2), 2.51-2.62 (2H,

2,3,4,9-tetrahydro-1H-xanthen-1one

m, CH2), 5.31 (1H, s, CH), 6.95-6.99 (2H, m, ArH), 7.05-

SC

9-(1H-indol-3-yl)-3,3-dimethyl-

7.18 (5H, m, ArH), 7.25 (1H, d, J = 4.0 Hz, ArH), 7.39 (1H, d, J = 8.0 Hz, ArH), 8.03 (1H, s, NH); 13C NMR (100

M AN U

MHz, CDCl3): δC (ppm) 27.67, 29.09, 29.48, 29.72, 32.09, 41.56, 50.94, 111.19, 112.72, 116.24, 119.07, 119.34, 120.51, 121.61, 122.36, 124.91, 125.28, 125.70, 127.41, 130.17, 136.55, 149.60, 164.29, 197.32. White crystalline solid (yield 88%); mp 206 °C; Rf 0.74 ether,

2:3);

FT-IR

(KBr)

νmax:

TE D

Br

(EtOAc:Petroleum

NH

3264,2955, 1737, 1639, 1580, 1486, 1455, 1379, 1228,

O

1178, 1152, 1025, 758, 627cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 0.98(1H, s, CH3), 1.11 (1H, s, CH3), 2.172.29 (2H, m, CH2), 2.53-2.64 (2H, m, CH2), 5.25 (1H, s,

EP

O 4b

9-(5-Bromo-1H-indol-3-yl)-3,3dimethyl-2,3,4,9-tetrahydro-1Hxanthen-1-one

AC C

1

CH), 6.98-7.02 (1H, m, ArH), 7.08-7.19 (6H, m, ArH), 7.51 (1H, d, J = 1.6 Hz, ArH), 8.19 (1H, s, NH); 13C NMR (100 MHz, CDCl3): δC (ppm) 27.43, 29.17, 29.32, 32.08, 41.56, 50.94, 112.43, 112.66, 116.46, 120.37, 121.70, 123.58, 124.51, 124.85, 125.02, 127.66, 130.02, 135.12, 149.44, 164.62, 197.42.

28

ACCEPTED MANUSCRIPT

White crystalline solid(yield 92%); mp 213 °C; Rf 0.77 NH

(EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3297, 3056, 2964, 2865, 1641, 1583, 1485, 1458, 1380, 1228,

O

1182, 1145, 1028, 762, 738 cm−1; 1H NMR (400 MHz,

RI PT

CDCl3): δH (ppm) 0.90 (3H,s, CH3), 1.08 (3H, s, CH3),

O 4c

2.10-2.20 (2H, m, ArH), 2.52 (3H, s, CH3), 2.59 (2H, d, J = 16 Hz), 5.23 (1H, s, CH), 6.86-6.94 (3H, m, ArH), 7.007.10 (4H, m, ArH), 7.20 (1H, d, J = 8 Hz, ArH), 7.90 (1H, 13

C NMR (100 MHz, CDCl3): δC (ppm) 11.92,

SC

s, NH);

27.67, 28.53, 29.08, 32.09, 41.54, 50.95, 110.37, 112.41, 115.75, 116.13, 117.94,119.03, 120.44, 124.89, 125.27,

M AN U

9-(2-Methyl-1H-indol-3-yl)-3,3dimethyl-2,3,4,9-tetrahydro-1Hxanthen-1-one

126.97, 127.33, 130.24, 131.45, 135.33, 149.56, 164.15, 197.61.

White crystalline solid (yield 88%); mp 232 °C; Rf 0.86 (EtOAc:Petroleum

ether,

2:3);

FT-IR

(KBr)

νmax:

3196,3049, 2962, 2893, 2869,1631, 1593, 1484, 1378,

OH O

TE D

1227, 1174, 1144, 1029, 754 cm−1; 1H NMR (400 MHz, DMSO-d6): δH (ppm) 0.94 (3H, s, CH3), 1.08 (3H, s, CH3),

O 4d

2.10 (1H, d, J = 16 Hz ), 2.34 (1H, d, J = 16.4 Hz ), 2.58 (1H, d, J = 17.6 Hz), 2.71 (1H, d, J = 17.2 Hz), 5.75 (s,

AC C

EP

9-(2-Hydroxynaphthalen-1-yl)3,3-dimethyl-2,3,4,9-tetrahydro1H-xanthen-1-one

1H, CH), 6.61 (1H, t, J = 7.2 H, ArH), 6.70 (1H, d, J = 8

Hz, ArH), 6.85-6.89 (1H, m, ArH), 7.00 (1H, d, J = 7.2 Hz, ArH), 7.38-7.50 (3H, m,ArH), 7.86 (2H,t, J = 9.6 Hz, ArH), 8.31 (1H, d, J = 8.4 Hz, ArH), 9.64 (1H, s, OH); 13C NMR (100 MHz, DMSO-d6): δC (ppm) 26.20, 28.36, 28.93, 31.86, 50.17, 112.83, 115.76, 117.08, 118.08, 119.13, 123.47, 124.77, 126.82, 127.24, 128.35, 128.50, 129.95, 130.84, 131.13, 131.37, 147.23, 153.56, 164.28, 196.17.

29

ACCEPTED MANUSCRIPT

White crystalline solid (yield 87%); mp226°C; Rf 0.77 (EtOAc:Petroleum ether, 2:3); λmax,

O HO

O O

341 nm; λmax,

emi

abs

= 278, 282, 310,

= 409, 435, 460 nm (in DCM); FT-IR

(KBr) νmax: 3318, 3192, 2948, 2920, 1678, 1637, 1580,

RI PT

1489, 1382, 1489, 1382, 1234, 1186, 1152, 1065, 751

O 4e

cm−1; 1H NMR (400 MHz, DMSO-d6): δH (ppm) 0.99 (3H, s, CH3), 1.07 (3H, s, CH3), 2.08 (1H,d, J = 16.4 Hz), 2.30 (1H, d, J = 16.0 Hz), 2.44 (1H, d, J = 17.6 Hz) 5.44 (1H, s, CH), 7.01-7.09 (3H, m, ArH), 7.20 (1H,t, J = 7 Hz, ArH),

SC

9-(4-Hydroxy-2-oxo-2Hchromene-3-yl)-3,3-dimethyl2,3,4,9-tetrahydro-1H-xanthen-1one

7.29-7.37 (2H, m, ArH), 7.58 (1H, t, J = 7.6 Hz, ArH),

M AN U

8.01 (1H, d, J = 6.8 Hz, ArH), 11.89 (1H, s, OH); NMR (100 MHz,

13

C

DMSO-d6): δC (ppm) 26.30, 27.32,

28.95, 31.71, 40.59, 50.20, 115.72, 116.03, 123.82, 124.49, 127.75, 128.59, 131.80, 152.04, 196.32. Yellow

solid

(yield

88%);

m.p255°C;

Rf

0.72

(EtOAc:Petroleum ether, 2:3); λmax, abs = 252, 277, 340 nm; λmax, emi = 410, 435, 460 nm (in DCM); FT-IR (KBr) νmax:

TE D

O

3184, 2959, 2920, 2850, 1674, 1632, 1578, 1485, 1462,

HO

O O

1364, 1275, 1230, 1185, 1035, 797, 756, 726 cm−1; 1H NMR (400 MHz, DMSO-d6): δH (ppm) 1.00 (3H, s, CH3),

1.07 (3H, s, CH3), 2.07 (1H, d, J = 15.6 Hz, CH2), 2.31

EP

O 4f

AC C

3-(3,3-Dimethyl-1-oxo-2,3,4,9tetrahydro-1H-xanthen-9-yl)-4hydroxy naphthalene-1,2-dione

(1H, d, J = 16 Hz, CH2), 2.43 (1H, d, J = 17.6 Hz, CH2), 2.63 (1H, d, J = 17.6 Hz, CH2), 5.38(1H, s, CH), 7.03-7.08 (3H, m, ArH),7.19-7.23 (1H, m, ArH), 7.78 (1H, t, J = 7.2 Hz, ArH), 7.81-7.87 (1H, m, ArH), 7.96 (1H, d, J = 7.2 Hz, ArH);

13

C NMR (100 MHz, DMSO-d6): δC (ppm)

26.38, 29.05, 31.72, 50.22, 109.67, 115.92, 124.73, 125.59, 127.89, 128.77, 129.79, 131.67, 133.22, 134.79, 149.41, 154.94, 165.59, 181.48, 183.35, 196.11.

30

ACCEPTED MANUSCRIPT

White crystalline solid (yield 86%); mp153 °C; Rf 0.70 O NH

1394, 1350, 1237, 1183, 1147, 1046, 1031, 851, 758 cm−1;

O O

1

H NMR (400 MHz, DMSO-d6): δH (ppm) 1.11 (3H, s,

RI PT

O

3198, 3081, 2958, 2859, 1712, 1648, 1619, 1575, 1438,

CH3), 1.15 (3H, s, CH3), 2.21 (2H,d, J = 16 Hz, CH2),

O 4g

2.34 (1H, d, J = 16 Hz, CH2), 2.43 (1H,d, J = 17.6 Hz,

5-(3,3-Dimethyl-1-oxo-2,3,4,9tetrahydro-1H-xanthen-9yl)pyrimidine-2,4,6(1H,2H,5H)trione

CH2), 2.53 (1H,d, J = 17.2 Hz, CH2), 3.68 (1H, s, CH), 4.72 (1H, s, CH), 6.99-7.15 (3H, m, ArH), 7.22-7.25 (1H,

SC

HN

(EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3448,

m, ArH), 10.95 (1H, s, NH), 11.25 (1H, s, NH); 13C NMR

M AN U

(100 MHz, DMSO-d6): δC (ppm) 31.81, 34.45, 36.92, 38.79, 46.15, 55.46, 59.32, 113.99, 121.55, 126.18, 129.94, 133.07, 133.68, 155.12, 155.54, 172.40, 173.71, 174.43, 201.72.

White solid (yield 93%); mp 209 °C; Rf 0.84 (EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3176, O

OH O

TE D

2953, 1640, 1592, 1489, 1372, 1312, 1259, 1230, 1188, 1023, 773, 754 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 0.99 (6H, s, (CH3)2), 1.03 (3H, s, CH3), 1.12 (3H, s,

EP

CH3), 1.91-2.01 (2H, m, CH2), 2.33 (2H, s, CH2), 2.36

O 4h

AC C

9-(2-Hydroxy-4,4-dimethyl-6oxocyclohex-1-enyl)-3,3dimethyl-2,3,4,9-tetrahydro-2Hxanthen-1-one

(2H, d, J = 3.2 Hz, CH2), 2.47 (1H, d, J = 17.6 Hz, CH2), 2.60 (1H, d, J = 17.6 Hz), 4.67 (1H, s, CH), 6.99-7.03 (3H, m, ArH), 7.14-7.18 (m, 1H), 10.49 (1H, s, OH);

13

C

NMR (100 MHz, CDCl3): δC (ppm) 26.45, 27.21, 27.79, 29.16, 29.71, 29.89, 30.95, 32.31, 41.55, 43.18, 49.93, 50.62, 111.05, 115.75, 118.33, 124.32, 124.58, 127.53, 127.98, 151.05, 169.18, 170.69, 196.58, 200.95.

31

ACCEPTED MANUSCRIPT

White crystalline solid (yield 88%); mp 257°C; Rf 0.74

NH

(EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3332, 3052, 2949,2861, 1634,1580, 1484, 1375, 1225, 1178,

O

1184, 1132, 1095, 757 cm−1; 1H NMR (400

MHz,

9-(1H-indol-3-yl)-2,3,4,9-

(2H, m, CH2), 2.62-2.73 (2H, m, CH2), 5.28 (1H, s, CH), 6.69-7.28 (8H, m, ArH), 7.40-7.43 (1H,m, ArH), 9.87 (1H, s, NH).

SC

tetrahydro-1H-xanthen-1-one

RI PT

DMSO-d6): δH (ppm) 2.00-2.05 (2H, m, CH2), 2.30-2.34

O 4i

White crystalline solid (yield 86%); mp 246 °C; Rf 0.73 (EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3412,

H N Br

O

M AN U

3123, 3062, 2950, 1633, 1587, 1486, 1456, 1374, 1232, 1182, 1085, 882, 791, 751 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 1.88-1.98 (2H, m, CH2), 2.27-2.31 (2H, O 4j

m, CH2), 2.58-2.71 (2H, m, CH2), 5.20 (1H, s, CH), 6.906.96 (2H, m, ArH), 7. 01-7.12 (6H, m, ArH), 7.44 (1H,d, J = 1.6 Hz, ArH), 8.23 (1H, s, NH);

13

C NMR (100 MHz,

TE D

9-(5-Bromo-1H-indol-3-yl)2,3,4,9-tetrahydro-1H-xanthen-1one

CDCl3): δC (ppm) 20.45, 27.86, 29.30, 37.10, 112.72, 113.80, 116.39, 120.31, 121.66, 123.84, 124.49, 124.93, 125.06, 127.46, 127.69, 129.99, 135.11, 149.47, 166.44,

EP

197.61.

AC C

H N

O

O 4k

9-(2-Methyl-1H-indol-3-yl)2,3,4,9-tetrahydro-1H-xanthen-1one

White crystalline solid (yield 90%); mp 238 °C; Rf 0.74 (EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3328, 3053, 2958, 1637, 1577, 1487, 1457, 1372, 1228, 1177, 1017, 792, 741 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 1.80-1.94 (2H, m, CH2), 2.22 (2H, t, J = 6.6 Hz), 2.49 (3H, s, CH3), 2.55-2.70 (2H, m, CH2), 5.18 (1H, s, CH), 6.82-7.16 (8H, m, ArH), 7.78 (1H, s, NH); 13C NMR (100 MHz, CDCl3): δC (ppm) 10.94, 19.43, 26.75, 27.47, 36.01, 109.29, 112.46, 114.76, 115.00, 116.79, 118.07, 119.39, 123.82, 124.23, 1226.02, 126.27, 129.10, 130.41, 32

ACCEPTED MANUSCRIPT

134.18, 148.40, 164.83, 196.54.

White crystalline solid (yield 81%); mp 214°C; Rf 0.70 N

abs

= 276, 338 nm;

RI PT

(EtOAc:Petroleum ether, 2:3); λmax,

λmax, emi = 410, 435, 462 nm (in DCM);FT-IR (KBr) νmax:

O

3496, 3044, 2931, 1731, 1638, 1600, 1482, 1450, 1369, 1223, 1177, 1150, 741, 639 cm−1; 1H NMR (400 MHz,

O 4l

CDCl3): δH (ppm) 1.94-2.03 (2H, m, CH2), 2.32-2.37 (2H, m, CH2), 2.63-2.76 (2H, m, CH2), 3.68 (3H, s, CH3), 5.32

SC

9-(1-Methyl-1H-indol-3-yl)2,3,4,9-tetrahydro-1H-xanthen-1one

(1H, s, CH), 6.95-7.00(3H, m, ArH), 7.08-7.19 (5H, m,

M AN U

ArH), 7.40 (1H, d, J = 8.0 Hz, ArH); 13C NMR (100 MHz, CDCl3): δC (ppm) 20.42, 27.87, 29.29, 32.63, 37.09, 109.25, 114.32, 116.19, 118.89, 119.15, 119.23, 121.18, 124.93, 125.60, 126.20, 127.21, 127.36, 130.13, 137.18, 149.66, 165.96, 197.39.

TE D

White crystalline solid (yield 83%); mp 212 °C; Rf 0.82 (EtOAc:Petroleum

OH O

ether,

2:3);

FT-IR

(KBr)

νmax:

3214,3069, 2963, 2893, 1627, 1590, 1484, 1375, 1225, 1186, 1096, 754 cm−1; 1H NMR (400 MHz, DMSO-d6): δH (ppm) 1.83-1.86 (1H, m, CH2), 1.97-2.01 (1H, m, CH2),

EP

O 4m

AC C

9-(2-Hydroxynaphthalen-1-yl)2,3,4,9-tetrahydro-1H-xanthen-1one

2.02-2.07 (2H, m, CH2), 2.73 (1H, d, J = 4.8 Hz), 5.75 (1H, s, CH), 6.58-6.70 (2H, m, ArH), 6.85-6.93 (2H, m, ArH), 7.36-7.81 (2H, m, ArH), 7.81-7.85 (2H, m, ArH), 8.19 (1H, d, J = 8.4 Hz, ArH), 9.72 (1H, s, OH).

33

ACCEPTED MANUSCRIPT

White crystalline solid (yield 80%); mp 206 °C; Rf 0.72 (EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3210, O

3028, 2972, 1697, 1643, 1570, 1486, 1455, 1386, 1292, HO

O O

1218, 1109, 756 cm−1; 1H NMR (400 MHz, CDCl3): δH

RI PT

(ppm) 1.93-2.05 (2H, m, CH2), 2.35-2.61 (3H, m, CH2), O

2.71-2.78 (1H, m, CH2), 5.00 (1H, s, CH), 6.95-7.02 (3H,

4n

m, ArH), 7.10-7.21 (3H, m, ArH), 7.37-7.39 (1H, m, ArH), 7.91-7.93 (1H, m, ArH), 11.19 (1H, s, OH);

13

C

NMR (100 MHz, CDCl3): δC (ppm) 19.98, 28.10, 28.58,

SC

9-(4-Hydroxy-2-oxo-2Hchromene-3-yl)- 2,3,4,9tetrahydro-1H-xanthen-1-one

35.99, 109.28, 111.30, 115.95, 116.19, 117.03, 122.50,

M AN U

123.70, 124.23, 125.03, 128.19, 128.49, 131.60, 151.21, 153.05, 160.97, 161.22, 171.90, 201.75. White solid (yield 90%); mp 227 °C; Rf 0.82 (EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 2970, O

2951, 2923, 2883, 1739, 1641, 1579, 1557, 1486, 1371,

OH O

1291, 1236, 1184, 1029, 775, 758 cm−1; 1H NMR (400

TE D

MHz, DMSO-d6): δH (ppm) 1.70-2.54 (12H, m, CH2), 5.07

(1H, s, CH), 6.81-6.99 (3H, m, ArH) 7.06-7.19 (1H, m,

O 4o

ArH), 10.48 (1H, br s, OH);

AC C

EP

9-(2-Hydroxy-6-oxo-cyclo hex-1enyl)- 2,3,4,9-tetrahydro-2Hxanthen-1-one

NH

O

Br

13

C

NMR (100 MHz,

DMSO-d6): δC (ppm) 25.57, 32.51, 41.88, 53.36, 117.20,

120.37, 121.59, 126.51, 129.34, 130.92, 131.95, 133.62, 154.81, 171.80, 201.24. White crystalline solid (yield 89%); mp 223 °C; Rf 0.72 (EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3349, 3056, 2922, 2883, 1641, 1575, 1476, 1372, 1227, 1173, 1063, 733 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 0.92 (3H, s, CH3), 1.08 (3H, s, CH3), 2.14-2.26 (2H, m,

O 4p

CH2), 2.49-2.60 (2H, m, CH2), 5.23 (1H, s, CH), 6.95-7.09 (4H, m, ArH), 7.21-7.25 (3H, m, ArH), 7.33 (1H, d, J =

9-(1H-indol-3-yl)-3,3-dimethyl-7-

8.0 Hz, ArH), 8.31 (1H, s, NH); 34

13

C NMR (100 MHz,

ACCEPTED MANUSCRIPT

bromo-2,3,4,9-tetrahydro-1H-

CDCl3): δC (ppm) 27.58, 29.12, 29.69, 32.10, 41.45,

xanthen-1-one

50.90, 111.50, 112.33, 117.31, 118.09, 118.76, 119.43 119.51, 121.69, 122.70, 125.47, 127.41, 130.51, 136.66,

RI PT

148.65, 164.11, 197.35. White crystalline solid (yield 86%); mp 202 °C; Rf 0.72 NH

Br

(EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3333, 2951, 2883, 1735, 1636, 1573, 1473, 1378, 1229, 1174,

O

1070, 1028, 797, 751 cm−1; 1H NMR (400 MHz, CDCl3):

Br

SC

δH (ppm) 0.96 (3H, s, CH3), 1.10 (3H, s, CH3), 2.22 (2H,

O 4q

d, J = 18.8 Hz, CH2), 2.57 (2H, d, J = 8.4 Hz, CH2), 5.18

M AN U

(1H, s, CH), 6.97-7.11 (4H, m, ArH), 7.21-7.25 (2H, m, ArH), 7.45 (1H, s, ArH), 8.57 (1H, s, NH); 13C NMR (100 9-(5-Bromo-1H-indol-3-yl)-3,3dimethyl-7-bromo-2,3,4,9tetrahydro-1H-xanthen-1-one

MHz, CDCl3): δC (ppm) 27.33, 29.17, 29.54, 32.08, 41.46, 50.91, 112.04, 112.76, 112.95, 117.43, 118.29, 119.32, 121.37, 123.90, 124.57, 126.94, 127.15, 130.76, 132.77, 135.25, 148.47, 164.49, 197.51; HRMS m/z (ESI) Calcd.

TE D

for C23H19Br2NO2 [M]+ 501.2105; Found 501.2100. White crystalline solid (yield 90%); mp 248 °C; Rf 0.76

(EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3331,

NH

2957, 1640, 1574, 1473, 1377, 1226, 1175, 1071, 1027,

Br

EP

O

AC C

O 4r

9-(2-Methyl-1H-indol-3-yl)-3,3dimethyl-7-bromo2,3,4,9tetrahydro-1H-xanthen-1-one

762, 738 cm−1; 1H NMR (400 MHz, DMSO-d6): δH (ppm)

0.81 (3H, s, CH3), 1.03 (3H, s, CH3), 2.02 (1H, d, J = 16 Hz), 2.24 (1H, d, J = 16.4 Hz ), 2.52 (1H, d, J = 4.8 Hz ), 2.56 (3H, s, CH3), 2.63 (1H, d, J = 17.6 Hz), 5.13 (1H, s, CH), 6.78 (1H, t, J = 7.4 Hz, ArH ), 6.89 (1H, t, J = 7.4 Hz, ArH ), 7.05 (1H, d, J = 7.2 Hz, ArH), 7.13-7.19 (3H, m, ArH), 7.33 (1H, d, J = 8.4 Hz, ArH), 10.80 (1H, s, NH);

13

C NMR (100 MHz, DMSO-d6): δC (ppm) 12.00,

26.92, 28.20, 29.24, 32.03, 50.63, 111.13, 111.85, 114.88, 116.69, 117.26, 118.80, 120.24, 126.66, 128.31, 130.81, 132.43, 132.74, 135.52, 148.80, 163.74, 196.52; HRMS 35

ACCEPTED MANUSCRIPT

m/z (ESI) Calcd. for C24H22BrNO2 [M]+ 436.3410; Found 436.3408. White crystalline solid (yield 82%); mp 264 °C; Rf 0.85 (EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3124,

RI PT

3057, 2961, 2882, 1627, 1589, 1474, 1380, 1266, 1222,

OH O

1182, 1143, 1033, 808, 755, 681 cm−1. 1H NMR (400

Br

MHz, DMSO): δH (ppm) 0.95 (3H, s, CH3), 1.07 (3H, s, O 4s

CH3), 2.12 (1H, d, J = 16 Hz), 2.34 (1H, d, J = 16.4 Hz), (1H, s, CH), 6.67 (1H, d, J = 8.2 Hz, ArH), 7.05 (1H, d, J = 8.4 Hz, ArH), 7.14 (1H, s, ArH), 7.39-7.45 (2H, m,

M AN U

9-(2-Hydroxynaphthalen-1-yl)3,3-dimethyl-7-bromo-2,3,4,9tetrahydro-1H-xanthen-1-one

SC

2.60(1H, d, J = 17.2 Hz), 2.71 (1H, d, J = 17.2 Hz) 5.71

ArH), 7.51 (1H, t, J = 7.6 Hz, ArH), 7.89 (2H, t, J = 8.2 Hz, ArH), 8.27 (1H, d, J = 8.4 Hz, ArH), 10.06 (1H, s, OH) ;

13

C NMR (100 MHz, DMSO): δC (ppm) 26.52,

29.40, 32.39, 50.65, 110.49, 112.69, 117.59, 118.39, 123.76, 125.40, 127.51, 128.96, 129.37, 130.49, 131.35,

TE D

131.51, 132.78, 134.28, 147.74, 153.79, 164.91, 196.54. White crystalline solid (yield 80%); mp 242 °C; Rf 0.74 (EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3212,

O

AC C

Br

O O

EP

HO

2952, 2890, 1670, 1614, 1563, 1476, 1379, 1231, 1195,

O 4t

9-(4-Hydroxy-2-oxo-2Hchromene-3-yl)-3,3-dimethyl-7bromo-2,3,4,9-tetrahydro-1Hxanthen-1-one

1062, 1021, 812, 761 cm−1; 1H NMR (400 MHz, DMSOd6+MeOD): δH (ppm) 0.97 (3H, s, CH3), 1.06 (3H, s, CH3), 2.08 (1H, d, J = 16 Hz, CH2), 2.29 (1H, d, J=17.2 Hz, CH2), 2.44 (1H, d, J = 17.6 Hz, CH2), 2.61 (1H, d, J = 17.2 Hz, CH2), 5.43 (1H, s, CH), 7.05 (1H, d, J = 8.8 Hz, ArH), 7.20 (1H, d, J = 2 Hz, ArH), 7.29 (1H, d, J = 8.4 Hz, ArH), 7.34-7.39 (2H, m, ArH), 7.57-7.61 (1H, m, ArH), 8.01 (1H, d, J = 8.4 Hz, ArH); 13C NMR (75 MHz, DMSO-d6): δC (ppm) 26.67, 29.35, 32.14, 50.16, 116.20, 116.51, 118.56, 124.27, 131.01, 131.20, 132.35, 149.74, 152.66, 196.86. 36

ACCEPTED MANUSCRIPT

White crystalline solid (yield 88%); mp 164 °C; Rf 0.73 (EtOAc:Petroleum ether, 2:3); λmax, abs = 249, 306, 370 nm; λmax, emi = 410, 434, 461 nm (in DCM); FT-IR (KBr) νmax: 3343, 2962, 2863, 1738, 1634, 1557, 1516, 1469, 1374,

NH

RI PT

1229, 1101, 1038, 779, 735 cm−1; 1H NMR (300 MHz, O

CDCl3): δH (ppm) 0.95 (3H,s, CH3), 1.09-1.14 (9H, m, (CH3)3), 2.20 (2H, d, J = 6.3 Hz, CH2), 2.54 (2H, d, J =

N Et

O 4u

6.6 Hz, CH2 ), 3.29 (4H, d, J = 6.9 Hz), 5.19 (1H, s, CH), 6.34 (2H, d, J= 8.1 Hz, ArH ), 6.95 (2H, d, J = 5.7 Hz,

SC

Et

M AN U

ArH ), 7.03-7.11 (2H, m, ArH), 7.24 (1H, d, J = 7.8 Hz, 9-(1H-indol-3-yl)-3,3-dimethyl-613 (diethylamino)-2,3,4,9-tetrahydro- ArH), 7.42 (1H, d, J = 7.5 Hz, ArH), 8.03 (1H, s, NH); C 2H-xanthen-1-one NMR (75 MHz, CDCl3): δC (ppm) 12.56, 27.78, 28.67, 29.01, 32.06, 41.74, 44.41, 51.01, 98.65, 109.38, 111.10, 111.98, 113.29, 119.37, 121.14, 121.38, 122.20, 125.91, 130.40, 136.61, 147.46, 150.48, 164.44, 197.47; HRMS m/z (ESI) Calcd. for C27H30N2O2 [M]+ 414.5393; Found

TE D

414.5390. Orange

solid

(yield

82%);

mp

190°C;

Rf

0.75

(EtOAc:Petroleum ether, 2:3); λmax, abs = 270, 307, 394 nm;

O

λmax, emi = 405, 430, 456 nm (in DCM); FT-IR (KBr) νmax:

HO

EP

N Et

O 4v

AC C

Et

O O

2-(6-diethylamino)- -2,3,4,9tetrahydro-3,3-dimethyl-1-oxo1H-xanthen-9-yl)-3-hydroxy naphthalene-1,4-dione

3229, 2962, 2923, 1675, 1644, 1562, 1515, 1462, 1367, 1273, 1226, 1102, 1039, 765, 728 cm−1; 1H NMR (400 MHz, CDCl3): δH (ppm) 1.05 (3H, s, CH3), 1.11-1.15 (10H, m, (C2H5)2), 1.21 (3H, s, CH3), 2.18-2.31 (2H, m, CH2), 2.52-2.58 (2H, m, CH2), 5.35 (1H, s, CH), 6.33 (2H, d, J = 8.0Hz, ArH ), 6.92 (1H, d, J = 8.4Hz, ArH), 7.597.69 (3H, m, ArH), 7.99-8.00 (1H, s, ArH), 8.08 (1H, s, OH); 13C NMR (100 MHz, CDCl3): δC (ppm) 12.57, 27.41, 28.69, 29.26, 32.12, 36.33, 38.24, 41.79, 44.35, 50.74, 53.10, 98.69, 108.75, 108.94, 110.62, 118.72, 118.84, 120.65, 125.85, 126.11, 126.96, 129.51, 132.69, 132.78, 37

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134.76, 147.91, 148.53, 150.82, 152.42, 166.84, 167.22, 182.11, 183.87, 192.12, 197.12, 197.47; HRMS m/z (ESI) Calcd. for C29H29NO5 [M]+ 471.5443; Found 471.5441.

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Red solid ; mp 185 °C; Rf 0.86 (EtOAc:Petroleum ether, 2:3); FT-IR (KBr) νmax: 3503, 3419, 3055, 1453, 1420, 1335, 1266, 1218, 1194, 1089, 740 cm-1; 1H NMR (300 MHz, CDCl3): δH (ppm) 5.45 (1H, brs, OH), 5.99 (1H, s, CH), 6.73 (1H, s, ArH), 6.86 (2H, t, J = 7.4 Hz, ArH),

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3,3’-[(27.02 (2H, t, J = 7.4Hz, ArH), 7.14-7.25 (5H, m, ArH), hydroxyphenyl)methylene]bis(1H- 7.96 (2H, s, 2(NH)); 13C NMR (75 MHz, CDCl ): δ 3 C indole) (ppm) 35.86, 111.25, 116.62, 117.18, 119.58, 119.90, 120.79, 123.66, 126.84, 128.03, 129.09, 129.98, 136.90, 154.51. 1 2

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2. Scanned copies of spectra

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Figure 1 1H NMR spectrum of compound 4a

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Figure 2 13C NMR spectrum of compound 4a

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Figure 31H NMR spectrum of compound 4b

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Figure 413C NMR spectrum of compound 4b

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Figure 51H NMR spectrum of compound 4c

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Figure 613C NMR spectrum of compound 4c

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Figure 7 1H NMR spectrum of compound 4d

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Figure 8 13C NMR spectrum of compound 4d

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Figure 9 1H NMR spectrum of compound 4e

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Figure 10 13C NMR spectrum of compound 4e

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Figure 11 1H NMR spectrum of compound 4f

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Figure 12 13C NMR spectrum of compound 4f

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Figure 13 1H NMR spectrum of compound 4g

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Figure 14 13C NMR spectrum of compound 4g

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Figure 15 1H NMR spectrum of compound 4h

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Figure 16 13C NMR spectrum of compound 4h

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Figure 17 1H NMR spectrum of compound 4i

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Figure 18 1H NMR spectrum of compound 4j

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Figure 19 13C NMR spectrum of compound 4j

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Figure 20 1H NMR spectrum of compound 4k

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Figure 21 13C NMR spectrum of compound 4k

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Figure 22ORTEP diagram of compound 4k 49

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Figure 23 1H NMR spectrum of compound 4l

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Figure 2413C NMR spectrum of compound 4l 50

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Figure 25 1H NMR spectrum of compound 4m

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Figure 26 1H NMR spectrum of compound 4n

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Figure 27 13C NMR spectrum of compound 4n

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Figure 28 1H NMR spectrum of compound 4o

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Figure 29 13C NMR spectrum of compound 4o

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Figure 30 1H NMR spectrum of compound 4p 53

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Figure 31 13C NMR spectrum of compound 4p

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Figure 32 1H NMR spectrum of compound 4q 54

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Figure 33 13C NMR spectrum of compound 4q

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Figure 34 FT-IR spectrum of compound 4q 55

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Figure 35 HRMS spectrum of compound 4q

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Figure 361H NMR spectrum of compound 4r 56

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Figure 3713C NMR spectrum of compound 4r

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Figure 38 FT-IR spectrum of compound 4r 57

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Figure 39 HRMS spectrum of compound 4r

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Figure 401H NMR spectrum of compound 4s 58

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Figure 4113C NMR spectrum of compound 4s

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Figure 421H NMR spectrum of compound 4t 59

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Figure 4313C NMR spectrum of compound 4t

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Figure 44 1H NMR spectrum of compound 4u 60

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Figure 45 13C NMR spectrum of compound 4u

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Figure 46 FT-IR spectrum of compound 4u 61

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Figure 47 HRMS spectrum of compound 4u

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Figure 48ORTEP diagram of compound 4u 62

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Figure 49 1H NMR spectrum of compound 4v

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Figure 50 13C NMR spectrum of compound 4v

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Figure 51 FT-IR spectrum of compound 4v

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Figure 52 HRMS spectrum of compound 4v

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Figure 53 1H NMR spectrum of compound 5a

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Figure 54 13C NMR spectrum of compound 5a 65

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Figure 55(a-e) Solvatochromism of compounds 4a (a), 4g (b), 4j (c), 4s (d), 4t (e) [Absorption]

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Highlights
Synthesis of new 4H-Chromenes via Multi Component Reaction

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Solvent free synthesis has been presented to reduce the use of organic solvents

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A reusable Amberlite IRA-400 Cl basic anion exchange resin catalyst is used

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Fluorescence and solvatochromism of the selective compounds were studied

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