THP/MOM/Ac/Ts ethers and concomitant regioselective ... Sumit Kumar*, Nishant Verma, Naseem Ahmed* Department

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Text of THP/MOM/Ac/Ts ethers and concomitant regioselective ... Sumit Kumar*, Nishant Verma, Naseem Ahmed*...

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    β-Cyclodextrin in water: Highly facile biomimetic one pot deprotection of phenolic

    THP/MOM/Ac/Ts ethers and concomitant regioselective cyclization of chalcone

    epoxides and 2’-aminochalcones

    Sumit Kumar*, Nishant Verma, Naseem Ahmed*

    Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, India

    *Corresponding author. Fax and Tel.: +91 1332 285745.

    E-mail address: sumitdcy@iitr.ac.in nasemfcy@iitr.ac.in

    Table of contents

    1. General methods

    2. General procedure for the deprotection of THP, MOM, acetyl and tosyl ethers and sequel cyclization of chalcone epoxide and 2’-aminochalcone

    3. Characterization data for selected synthesized compounds

    4. 1H and 13C NMR Spectra

    Electronic Supplementary Material (ESI) for RSC Advances. This journal is © The Royal Society of Chemistry 2015

    mailto:sumitdcy@iitr.ac.in mailto:nasemfcy@iitr.ac.in

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    1. General methods

    All the required chemicals were purchased from Merck and Aldrich Chemical Company. Pre-

    coated aluminium sheets (silica gel 60 F254, Merck) were used for thin-layer

    chromatography (TLC) and spots were visualized under UV light. Silica gel column

    chromatography was performed using silica gel 60–120 mesh size (RANKEM Limited). IR

    spectra were recorded with KBr on Thermo Nicolet FT-IR spectrophotometer. 1H NMR and

    13C NMR spectra were recorded on Jeol ECX 400 MHz and Bruker Spectrospin DPX 500

    MHz spectrometer using CDCl3 as a solvent and trimethylsilane (TMS) as an internal

    standard. Spectra were processed using Bruker Topspin® 3.0.b.8. Splitting patterns are

    designated as follows; s = singlet, d = doublet, dd = doublets of doublet, m = multiplet, br =

    broad. Chemical shift (δ) values are given in ppm. Mass spectra were collected using a direct

    inlet system (70 eV) with a VL detector (ES, 4000 V) on Perkin Elmer GC-MS. High-

    resolution mass spectra (HRMS) were obtained on a Brüker micrOTOF™-Q II mass

    spectrometer (ESIMS).

    Microwave Irradiation Experiment. All microwave experiments were carried out in a

    dedicated Anton Paar Monowave 300 reactor®, operating at a frequency of 2.455 GHz with

    continuous irradiation power of 0 to 850 W. The reactions were performed in a G-30

    Borosilicate glass vial sealed with Teflon septum and placed in a microwave cavity. Initially,

    microwave of required power was used and temperature was being ramped from room

    temperature to a desired temperature. Once this temperature was attained, the process vial

    was held at this temperature for required time. The reactions were continuously stirred.

    Temperature was measured by an IR sensor. After the experiments a cooling jet cooled the

    reaction vessel to ambient temperature.

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    2. General procedure for the microwave-assisted deprotection of THP, MOM, acetyl

    and tosyl ethers and concomitant cyclization of chalcone epoxides and 2’-

    aminochalcones: The substrate (1 mmol) dissolved in water (2 mL) was added to an aqueous

    solution of β-cyclodextrin (10 mol% in 10 mL of water) kept in a G-30 process vial and

    capped with Teflon septum. After a pre-stirring for one minute, the vial was subjected to

    microwave irradiation with the holding temperature of 60 °C for the prescribed time (Table 3

    and 4). After completion of reaction, the mixture was cooled to room temperature and

    extracted with EtOAc (3 × 15 mL) and the catalyst was filtered off and washed with EtOAc

    (2×10 ml), filterate was dried over anhydrous Na2SO4 and concentrated under reduced

    pressure. The crude product was purified by silica gel column chromatography using

    hexane/ethyl acetate (8:2) as an eluent if required otherwise compounds were pure enough for

    the spectral elucidation.

    3. Characterization data for representative compounds

    (a) Spectral data of THP, MOM, OAc and OTs deprotected products:

    (E)-3-(4-chlorophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one (5a)

    1H NMR (CDCl3, 500 MHz, ppm) δ 7.99 ( d, J = 8 Hz, 2H), 7.77

    (d, J = 15.5 Hz, 1H), 7.63 (t, J = 8Hz, 2H), 7.46 (d, J = 15.5 Hz,

    1H), 7.10 (t, J = 8.5 Hz, 2H), 6.95 (d, J = 8 Hz, 2H), 5.38 (s, 1H,

    D2O exchangeable). 13C NMR (CDCl3, 125 MHz, ppm) δ 186.88, 162.05, 141.32, 131.41,

    130.90, 130.83, 128.92, 121.85, 115.81, 115.21. IR (KBr, νmax = cm-1): 3410, 2926, 2875,

    1686, 1599, 1265, 1078, 862, 730. GC-MS (m/z): 302 [M+., C15H11BrO2], 304 [M+2].

    (E)-3-(4-bromophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one (6a)

    1H NMR (CDCl3, 500 MHz, ppm) δ 7.99 ( d, J = 8 Hz, 2H), 7.77

    (d, J = 15.5 Hz, 1H), 7.63 (t, J = 8Hz, 2H), 7.46 (d, J = 15.5 Hz,

    1H), 7.10 (t, J = 8.5 Hz, 2H), 6.95 (d, J = 8 Hz, 2H), 5.48 (s, 1H,

    O

    OH

    Cl

    O

    Br

    OH

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    D2O exchangeable). 13C NMR (CDCl3, 125 MHz, ppm) δ 186.88, 162.05, 141.32, 131.41,

    130.90, 130.83, 128.92, 121.85, 115.81, 115.21. IR (KBr, νmax = cm-1): 3410, 2926, 2875,

    1686, 1599, 1265, 1078, 862, 730. GC-MS (m/z): 302 [M+., C15H11BrO2], 304 [M+2].

    (E)-3-(4-hydroxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (7a)

    1H NMR (CDCl3, 500 MHz, ppm) δ 8.03 (d, J = 8 Hz, 2H), 7.74

    (d, J = 15.5 Hz, 1H), 7.56 (d, J = 8.5 Hz, 2H), 7.51 (d, J = 16

    Hz, 1H), 7.38 (d, J = 8.5 Hz, 2H), 6.98 (d, J = 9 Hz, 2H), 5.48

    (s, 1H, D2O exchangeable), 3.89 (s, 3H). 13C NMR (CDCl3, 125 MHz, ppm) δ 188.2, 163.9,

    142.7, 131.4, 131.3, 130.1, 121.5, 116.8, 116.6, 114.2, 55.1. IR (KBr, νmax = cm-1): 3410,

    2928, 2880, 1684, 1599, 1265. GC-MS (m/z): 254 [M+, C16H14O3].

    (E)-1-(4-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (8a)

    1H NMR (CDCl3, 500 MHz, ppm) δ 8.03 (d, J = 8 Hz, 2H), 7.77

    (d, J = 16 Hz, 1H), 7.55 (d, J = 8Hz, 2H), 7.42 (d, J = 15.5 Hz,

    1H), 6.98 (d, J = 8 Hz, 2H), 6.89 (d, J = 8 Hz, 2H), 5.82 (s, 1H,

    D2O exchangeable), 3.89 (s, 3H). 13C NMR (CDCl3, 125 MHz, ppm) δ 188.7, 163.6, 142.8,

    131.2, 131.0, 130.4, 121.7, 116.3, 116.2, 114.0, 55.7. IR (KBr, νmax = cm-1): 3410, 2926,

    2875, 1686, 1599, 1265. GC-MS (m/z): 254 [M+, C16H14O3].

    (E)-1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (9a)

    1H NMR (CDCl3, 400 MHz, ppm) δ 7.91-7.86 (m, 2H), 7.61 (d, J

    = 8.8 Hz, 2H), 7.52 (d, J = 15.6 Hz, 1H), 7.49-7.45 (m, 2H), 7.00

    (dd, J = 1.2, 8.8 Hz, 1H), 6.93 (d, J = 8.4 Hz, 2H), 3.84 (s, 3H),

    1.68 (s, 1H, D2O exchangeable). 13C NMR (CDCl3, 100 MHz, ppm) δ 193.8, 163.7, 162.1,

    145.5, 136.3, 130.7, 129.7, 127.4, 120.2, 118.9, 118.7, 117.7, 114.6, 55.6. IR (KBr, νmax =

    cm-1): 3410, 2926, 2875, 1686, 1599, 1265. GC-MS (m/z): 254 [M+, C16H14O3].

    O

    OCH3

    HO

    O

    OCH3

    OH

    O

    H3CO

    OH

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    (E)-1-(4-chlorophenyl)-3-(2-hydroxyphenyl)prop-2-en-1-one (12a)

    1H NMR (CDCl3, 400 MHz, ppm) δ 7.92-7.84 (m, 2H), 7.64-

    7.58 (m, 3H), 7.53-7.49 (m, 1H), 7.41 (d, J = 8.8 Hz, 2H), 7.01

    (d, J = 8.4 Hz, 1H), 6.95 (d, J = 7.2 Hz, 2H), 4.84 (s, 1H, D2O

    exchangeable). 13C NMR (CDCl3, 100 MHz, ppm) δ 193.6,

    163.8, 144.1, 136.7, 133.2, 131.7, 130.0, 129.8, 129.5, 129.0, 120.7, 119.1, 118.9. IR (KBr,

    νmax = cm-1): 3410, 2926, 2875, 1686, 1599, 1265. GC-MS (m/z): 258 [M+, C15H11ClO2], 260

    [M+2]+.

    2,5-dihydroxy-3-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (16a)

    1H NMR (CDCl3, 500 MHz, ppm) δ 7.92 (dd, J = 1.5, 7 Hz, 2H), 7.55-

    7.52 (m, 2H), 7.07-7.01 (m, 3H), 5.31 (d, J = 2 Hz, 1H), 5.22 (d, J = 2

    Hz, 1H), 4.19 (s, 1H, D2O exchangeable), 3.91 (s, 3H), 1.61 (s, 1H,

    D2O exchangeable). 13C NMR (CDCl3, 125 MHz, ppm) δ 195.9, 162.6,

    162.2, 136.8, 134.8, 131.4, 129.3, 128.9, 125.6, 116.7, 115.8, 75.4, 63.6, 53.7. IR (KBr, νmax

    = cm-1): 3408, 2925, 2879, 1685, 1595, 1266, 1089, 858, 731. GC-MS (m/z): 270 [M+,

    C16H14O4].

    3-(4-bromophenyl)-2,5-dihydroxy-2,3-dihydro-1H-inden-1-one (18a)

    1H NMR (CDCl3, 500 MHz, ppm) δ 7.93 (m, 2H), 7.70-7.67 (m, 1H),

    7.58-7.53 (m, 2H), 7.08-7.04 (m, 2H), 6.10 (s, 1H, D2O

    exchangeable), 5.37 (d, J = 2 Hz, 1H), 5.22 (d, J = 2.5 Hz, 1H), 4.15

    (s, 1H, D2O exchangeable). 13C NMR (CDCl3, 125 MHz, ppm) δ

    195.6, 161.9, 137.4, 132.4, 131.9, 131.5, 130.0, 129.8, 126.0, 123.1, 116.3, 75.4, 63.6. IR

    (KBr, νmax = cm-1): 3433, 2935, 2877, 1687, 1585, 1266, 1088, 862, 733. GC-MS (m/z): 318

    [M+, C15H11BrO3], 320 [M+2]+.

    Cl

    O

    OH

    O

    OH

    OCH3

    HO

    O

    OH HO

    Br

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    5-chloro-2-hydroxy-3-(4-hydroxyphenyl)-2,3-dihydro-1H-inden-1-one (20a)

    1H NMR (CDCl3, 500 MHz, ppm) δ 7.92 (m, 2H), 7.68 (d, J = 7.5 Hz,

    1H), 7.58-7.50 (m, 2H), 7.43 (d, J = 8.5 Hz, 2H), 5.36 (d, J = 1.5 Hz, 1H),

    5.19 (d, J = 2 Hz, 1H), 4.13 (s, 1H, D2O exchangeable), 1.81 (s, 1H, D2O

    exchangeable). 13C NMR (CDCl3, 125 MHz, ppm) δ 195.7, 162.4, 161.5,

    136.7, 134.7, 131.4, 130.5, 129.4, 128.8, 125.3, 116.2, 75.4, 63.6. IR (KBr, νmax = cm-1):

    3417, 2931, 2871, 1681, 1597, 1263, 1081, 860, 737. GC-MS (m/z): 274 [M+, C15H11ClO3],

    276 [M+2]+.

    5-bromo-2-hydroxy-3-(4-hydroxyphenyl)-2,3-dihydro-1H-inden-1-one (21a)

    1H NMR (CDCl3, 500 MHz, ppm) δ 7.91 (dd, J = 1,