7KLVS4 4a 3e 76.1, 77.9, 108.8, 112.9, 122.1, 122.5, 123.4, 123.5, 126.3, 129.1, 129.3, 130.2,...
Transcript of 7KLVS4 4a 3e 76.1, 77.9, 108.8, 112.9, 122.1, 122.5, 123.4, 123.5, 126.3, 129.1, 129.3, 130.2,...
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Supporting Information
for
Copper-catalyzed synthesis of spiro-indolofurobenzopyrans:
tandem reactions of diazoamides and O-propargyl salicylaldehydes
Sengodagounder Muthusamya,* Ammasi Prabua and Eringathodi Sureshb
aSchool of Chemistry, Bharathidasan University, Tiruchirappalli-620 024, India
bCSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar-364002, India
* Tel: +91-431-2407053; Fax: +91-431-2407045; E-mail: [email protected]
CONTENTS
General information S2
General procedure for spiro-indolooxiranes 3 S2
Characterization of the product 3 S3-S4
General procedure for spiro-indolofurobenzopyrans 4 S4
Characterization of the product 4 S4-S14
Procedure for the synthesis of compound 5 S14
Characterization of the product 5-9 S14-S16
1H and 13C NMR spectra of the product 3 S17-S22
1H and 13C NMR spectra of the product 4 S23-S58
1H and 13C NMR spectra of the products 5-9 S59-S68
Solid-state arrangement of compound 4i S69-S70
Energy minimization MM2 calculations S71
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2019
mailto:[email protected]
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General information
Melting points were determined on a capillary melting point apparatus and uncorrected. IR
spectra were recorded using ATR technique on a Bruker Alpha FT-IR spectrophotometer. All
compounds were fully characterized. Proton nuclear magnetic resonance (1H NMR) spectra were
recorded at 400 MHz using CDCl3 in ppm (δ) related to tetramethylsilane (δ=0.00) as an internal
standard and are reported as follows; chemical shift (ppm), multiplicity (br = broad, s = singlet, d
= doublet, t = triplet, dd = doublet of doublet, m = multiplet), ABq = AB quartet, ABqd = AB
quartet of doublet and coupling constant (Hz). Carbon-13 nuclear magnetic resonance (13C
NMR) spectra were recorded at 100 MHz in CDCl3. Chemical shifts are reported in delta (δ)
units, parts per million (ppm) relative to the center of the triplet at 77.7 ppm for CDCl3. Carbon
types were determined from 13C NMR and DEPT experiments. The residual solvent signals were
used as references and the chemical shifts converted to the TMS scale (CDCl3: δH = 7.26 ppm, δC
= 77.7 ppm). High resolution mass analyses were performed using electrospray ionization (ESI)
technique on a Thermo Exactive Orbitrap mass spectrometer. All solvents were purified by
distillation following standard procedure. Thin layer chromatography was performed on silica or
alumina plates and components visualized by observation under iodine/UV light at 254 nm.
Column chromatography was performed on silica gel (100-200 mesh). All the reactions were
conducted in oven-dried glassware under a positive pressure of nitrogen with magnetic stirring.
Reagents were added via syringes through septa. The propargyl bromide (80% solution in
toluene), DMAD, NPM, Rh2(OAc)4, Cu(I)TC and other commercial chemicals were purchased
from M/s Sigma Aldrich and used as provided. The o-hydroxyaldehydes were purchased from
Aldrich and Alfa Aesar Chemicals. K2CO3 was dried by heating at 110 °C for 12 h and left to
cool under nitrogen atmosphere.
Experimental Section
General experimental procedure I for the synthesis of spiro-indolooxiranes (3)
To an oven-dried flask, a solution containing the appropriate aldehyde 2 (1.1 mmol) and 5 mol%
of copper(I) thiophenecarboxylate dissolved in 5 mL of dry DCE under a nitrogen atmosphere
was added a solution of 3-diazoindol-2-one 1 (1 mmol) in dry DCE (4 mL) at ambient
temperature to afford until the reaction completed (monitored using TLC). After the completion
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3a
3b
of reaction, the solvent was removed under reduced pressure. The residue was subjected to
column chromatography (silica gel, 100-200 mesh, EtOAc/hexane 30:70) to furnish spiro-
indolooxiranes 3.
Synthesis of 1-benzyl-3'-(2-(prop-2-yn-1-yloxy)phenyl)spiro[indoline-3,2'-oxiran]-2-one (3a)
A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry dichloroethane (4
mL) was added quickly to a solution containing 2-[(prop-2-yn-1-yl)oxy]benzaldehyde 2a (71
mg, 0.44 mmol) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg, 5
mol%) at ambient temperature to afford 3a (130 mg, 85%) as a white solid according to general
procedure I. Rf = 0.28 (EtOAc/hexane = 1:4, v/v); mp 104-105 °C; IR (neat): νmax 3287, 2924,
2118(w), 1724, 1610, 1462, 1354, 1022, 748 cm−1; 1H NMR (CDCl3, 400
MHz) δ = 2.41 (t, J = 2.4 Hz, 1H, ≡CH), 4.62 (ABqd, ΔδAB = 0.03, J1 = 16
Hz, J2 = 2 Hz, 2H, OCH2), 4.81-4.89 (m, 3H, NCH2/OCH), 6.77 (d, J = 8
Hz, 1H, ArH), 7.00 (d, J = 8.4 Hz, 1H, ArH), 7.07-7.15 (m, 2H, ArH), 7.24-
7.31 (m, 7H, ArH), 7.33-7.37 (m, 1H, ArH), 7.78 (d, J = 7.6 Hz, 1H, ArH)
ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.0, 56.0, 61.5, 64.0, 75.7, 78.4,
109.6, 111.5, 121.1, 121.6, 121.9, 122.6, 123.7, 127.4, 127.7, 128.8, 129.0, 129.6, 130.0, 135.6,
143.8, 155.5, 170.3 ppm; HRMS (ESI) Calculated for C25H19NO3 (M+Na)+: 404.1263 found:
404.1251.
Synthesis of 3'-(5-chloro-2-(prop-2-yn-1-yloxy)phenyl)-1-ethylspiro[indoline-3,2'-oxiran]-2-
one (3b)
A solution of 3-diazo-1-ethylindolin-2-one 1b (100 mg, 0.53 mmol) in dry dichloroethane (4
mL) was added quickly to a solution containing 5-chloro-2-(prop-2-yn-1-yloxy)benzaldehyde 2b
(114 mg, 0.58 mmol) ) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (5 mg,
5 mol%) at ambient temperature to afford 3b (148 mg, 79%) as a white
solid according to general procedure I. Rf = 0.33 (EtOAc/hexane = 1:4,
v/v); mp 157-158 °C; IR (neat): νmax 3292, 2924, 2123(w), 1727, 1617,
1484, 1364, 1019, 761 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 1.22 (t, J =
7.2 Hz, 3H, CH3), 2.42 (t, J = 2.4 Hz, 1H, ≡CH), 3.66-3.76 (m, 2H, NCH2),
4.55-4.64 (m, 2H, OCH2), 4.74 (s, 1H, CH), 6.90-6.93 (m, 2H, ArH), 7.09-
7.13 (m, 1H, ArH), 7.23-7.29 (m, 2H, ArH), 7.40 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H, ArH), 7.75
(d, J = 2.4 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 12.6, 35.0, 56.3, 61.4, 62.9,
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4a
3e
76.1, 77.9, 108.8, 112.9, 122.1, 122.5, 123.4, 123.5, 126.3, 129.1, 129.3, 130.2, 143.9, 154.1,
169.5 ppm; HRMS (ESI) Calculated for C20H1635ClNO3 (M+Na)
+: 376.0716 found: 376.0715.
Synthesis of 1-benzyl-3'-(5-nitro-2-(prop-2-yn-1-yloxy)phenyl)spiro[indoline-3,2'-oxiran]-2-
one (3e)
A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry dichloroethane (4
mL) was added quickly to a solution containing 5-nitro-2-(prop-2-yn-1-yloxy)benzaldehyde 2d
(90 mg, 0.44 mmol) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg, 5
mol%) at ambient temperature conditions to afford 3e (138 mg, 81%) as a white solid according
to general procedure I. Rf = 0.21 (EtOAc/hexane = 1.5:3.5, v/v); mp 187-189 °C; IR (neat): νmax
3287, 2923, 2124(w), 1725, 1613, 1418, 1341, 1268, 1006, 742 cm−1; 1H
NMR (CDCl3, 400 MHz) δ = 2.52 (t, J = 2.4 Hz, 1H, ≡CH), 4.73-4.74 (m,
2H, OCH2), 4.79-4.89 (m, 3H, OCH/NCH2), 6.81 (d, J = 8 Hz, 1H, ArH),
7.08-7.13 (m, 2H, ArH), 7.23-7.32 (m, 8H, ArH), 8.26 (dd, J1 = 6.8 Hz, J2
= 2.4 Hz, 1H, ArH), 8.68 (d, J = 2.8 Hz, 1H, ArH) ppm; 13C NMR (CDCl3,
100 MHz) δ = 44.1, 56.6, 61.4, 62.5, 76.8, 77.4, 109.8, 111.4, 122.1.
122.8, 122.9, 125.5, 125.7, 127.3, 127.8, 128.9, 130.5, 135.3, 141.8, 143.9, 159.8, 169.7 ppm;
HRMS (ESI) Calculated for C25H18N2O5 (M+H)+: 427.1294 found: 427.1285.
General experimental procedure II for the synthesis of spiro-indolofurobenzopyrans (4)
To an oven-dried flask, a solution containing the appropriate aldehyde 2 (1.1 mmol) and 5 mol%
of copper(I) thiophenecarboxylate dissolved in 5 mL of dry dichloroethane under a nitrogen
atmosphere was added a solution of 3-diazoindol-2-one 1 (1 mmol) in dry DCE (4 mL) using
syringe pump with the rate of addition of 0.5 mL/h at reflux conditions and continued until the
reaction completed (monitored using TLC). After the completion of reaction, the solvent was
removed under reduced pressure. The residue was subjected to column chromatography (silica
gel, 100-200 mesh, EtOAc/hexane 15:85) to furnish spiro-indolobenzofuropyrans 4.
Synthesis of 1'-benzyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-
indol]-2'(1'H)-one (4a)
A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry
dichloroethane (4 mL) was added dropwise to a solution containing 2-
[(prop-2-yn-1-yl)oxy]benzaldehyde 2a (71 mg, 0.44 mmol) dissolved in dry
DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg, 5 mol%) at reflux
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4b
4c
conditions to afford 4a (129 mg, 84%) as a white solid according to general procedure II. Rf =
0.35 (EtOAc/hexane = 1:4, v/v); mp 114-115 °C; IR (neat): νmax 2924, 1723, 1613, 1490, 1360,
1215, 745 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.90 (ABq, ΔδAB = 0.04, J = 15.6 Hz, 2H,
CH2), 5.62 (s, 1H, CH), 6.30 (s, 1H, CH), 6.70 (d, J = 8 Hz, 1H, ArH), 6.89-6.99 (m, 4H, ArH),
7.15-7.27 (m, 4H, ArH), 7.28-7.38 (m, 4H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.1,
63.7, 81.4, 92.7, 109.5, 116.8, 121.5, 121.8, 123.4, 125.5, 126.0, 126.8, 127.4, 127.8, 128.3,
128.9, 129.2, 130.4, 135.4, 139.9, 142.7, 152.8, 175.2 ppm; HRMS (ESI) Calculated for
C25H19NO3 (M+H)+: 382.1443 found: 382.1439.
Synthesis of 7-chloro-1'-ethyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-
one (4b)
A solution of 3-diazo-1-ethylindolin-2-one 1b (100 mg, 0.53 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 5-chloro-2-(prop-2-yn-1-yloxy)benzaldehyde
2b (114 mg, 0.58 mmol) dissolved in dry DCE (5 mL) and copper(I)
thiophenecarboxylate (5 mg, 5 mol%) at reflux conditions to afford 4b
(135 mg, 72%) as a white solid according to general procedure II. Rf =
0.23 (EtOAc/hexane = 1:4, v/v); mp 186-187 °C; IR (neat): νmax 2929,
1722, 1612, 1474, 1361, 1216, 754 cm−1; 1H NMR (CDCl3, 400 MHz) δ
= 1.30 (t, J = 7.2 Hz, 3H, CH3), 3.68-3.84 (m, 2H, NCH2), 4.96 (s, 2H,
CH2), 5.59 (s, 1H, CH), 6.19 (s, 1H, CH), 6.82-6.86 (m, 2H, ArH), 6.92-6.94 (m, 1H, ArH) 6.97-
7.10 (m, 1H, ArH), 7.17 (dd, J1 = 8.8 Hz, J2 = 2.8 Hz, 1H, ArH), 7.29-7.34 (m, 2H, ArH) ppm;
13C NMR (CDCl3, 100 MHz) δ = 12.6, 35.0, 63.8, 80.8, 92.7, 108.6, 118.2, 122.4, 123.2, 125.6,
126.3, 126.4, 127.4, 128.2, 129.2, 130.6, 138.8, 142.7, 151.4, 174.4 ppm; HRMS (ESI)
Calculated for C20H1635ClNO3 (M+H)
+: 354.0897 found: 354.0896.
Synthesis of 7-chloro-1'-benzyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-
one (4c)
A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in
dry dichloroethane (4 mL) was added dropwise to a solution containing
5-chloro-2-(prop-2-yn-1-yloxy)benzaldehyde 2b (85 mg, 0.44 mmol)
dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg,
5 mol%) at reflux conditions to afford 4c (114 mg, 69%) as a white solid
according to general procedure II. Rf = 0.29 (EtOAc/hexane = 1:4, v/v);
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4d
mp 201-202 °C; IR (neat): νmax 2966, 1724, 1650, 1470, 1361, 1211, 751 cm−1; 1H NMR (CDCl3,
400 MHz) δ = 4.91-5.06 (m, 4H, CH2), 5.69 (s, 1H, CH), 6.28 (s, 1H, CH), 6.76 (d, J = 7.6 Hz,
1H, ArH), 6.89 (d, J = 8.8 Hz, 1H, ArH), 6.97-7.03 (m, 2H, ArH), 7.20-7.26 (m, 2H, ArH), 7.30-
7.39 (m, 6H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.1, 63.8, 80.9, 92.8, 109.6, 118.3,
122.4, 123.5, 125.5, 126.3, 126.5, 127.3, 127.4, 127.8, 127.9, 128.9, 129.2, 130.6, 135.3, 139.1,
142.7, 151.4, 174.9 ppm; HRMS (ESI) Calculated for C25H1835ClNO3 (M+H)
+: 416.1054 found:
416.1054.
Synthesis of 7-bromo-1'-propyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-
one (4d)
A solution of 3-diazo-1-propylindolin-2-one 1c (100 mg, 0.50 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 5-bromo-2-(prop-2-yn-1-yloxy)benzaldehyde
2c (130 mg, 0.55 mmol) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (5
mg, 5 mol%) at reflux conditions to afford 4d (126 mg, 61%) as a white solid according to
general procedure II. Rf = 0.29 (EtOAc/hexane = 1:4, v/v); mp 167-168
°C; IR (neat): νmax 2923, 1725, 1613, 1472, 1341, 1090, 744 cm−1; 1H
NMR (CDCl3, 400 MHz) δ = 0.99 (t, J = 7.4 Hz, 3H, CH3), 1.69-1.78
(m, 2H, CH2), 3.67 (t, J = 7.2 Hz, 2H, CH2), 4.96 (ABq distorted, 2H,
CH2), 5.60 (s, 1H, CH), 6.19 (s, 1H, CH), 6.78 (d, J = 8.8 Hz, 1H, ArH),
6.84 (d, J = 7.8 Hz, 1H, ArH), 6.92-6.94 (m, 1H, ArH), 6.97-7.01 (m,
1H, ArH), 7.29-7.33 (m, 2H, ArH), 7.46 (s, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ =
11.4, 20.7, 41.9, 63.8, 80.7, 92.7, 108.8, 113.5, 118.7, 122.5, 123.2, 125.6, 127.8, 128.0, 129.4,
130.6, 132.1, 138.8, 143.1, 151.9, 174.7 ppm; HRMS (ESI) Calculated for C21H1879BrNO3
(M+Na)+: 434.0368 found: 434.0364.
Synthesis of 7-nitro-1'-benzyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-
one (4e)
A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 5-nitro-2-(prop-2-yn-1-yloxy)benzaldehyde 2d
(90 mg, 0.44 mmol) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg, 5
mol%) at reflux conditions to afford 4e (121 mg, 71%) as a white solid according to general
procedure II. Rf = 0.19 (EtOAc/hexane = 1.5:3.5, v/v); mp 199-200 °C; IR (neat): νmax 2981,
1718, 1612, 1465, 1357, 1213, 1088, 734 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.96 (s, 2H,
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4e
4f
4g
CH2), 5.16 (ABq, ΔδAB = 0.04, J = 13.2 Hz, 2H, CH2), 5.78 (s, 1H, CH), 6.31 (s, 1H, CH), 6.77
(d, J = 8 Hz, 1H, ArH), 6.91 -6.93 (m, 1H, ArH), 6.97-7.04 (m, 2H, ArH), 7.23-7.27 (m, 1H,
ArH), 7.33-7.42 (m, 5H, ArH), 8.17 (dd, J1 = 9.2 Hz, J2 = 2.8 Hz, 1H,
ArH), 8.34 (d, J = 2.8 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz)
δ = 44.1, 64.5, 80.1, 92.9, 109.7, 117.6, 123.42, 123.46, 123.6, 125.1,
125.3, 126.2, 127.3, 127.9, 129.0, 130.7, 135.2, 137.5, 142.0, 142.8,
158.0, 174.56 ppm; HRMS (ESI) Calculated for C25H18N2O5 (M+H)+:
427.1294 found: 427.1281.
Synthesis of 6-methoxy-1'-(prop-2-yn-1-yl)-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-
indol]-2'(1'H)-one (4f)
A solution of 3-diazo-1-(prop-2-yn-1-yl)indolin-2-one 1d (100 mg, 0.51 mmol) in dry
dichloroethane (4 mL) was added dropwise to a solution containing 3-methoxy-2-(prop-2-yn-1-
yloxy)benzaldehyde 2e (106 mg, 0.56 mmol) dissolved in dry DCE (5 mL)
and copper(I) thiophenecarboxylate (5 mg, 5 mol%) at reflux conditions to
afford 4f (119 mg, 65%) as a white solid according to general procedure II.
Rf = 0.13 (EtOAc/hexane = 1:4, v/v); mp 195-196 °C; IR (neat): νmax 3291,
2930, 1725, 1614, 1362, 1264, 1020, 733 cm−1; 1H NMR (CDCl3, 400
MHz) δ = 2.27 (s, 1H, CH), 3.90 (s, 3H, CH3), 4.49 (ABqd, ΔδAB = 0.13, J1
= 18 Hz, J2 = 2 Hz, 2H, CH2), 5.04 (ABq, ΔδAB = 0.08, J = 13.2 Hz, 2H,
CH2), 5.60 (s, 1H, CH), 6.26 (s, 1H, CH), 6.84-7.05 (m, 6H, ArH), 7.30-7.34 (m, 1H, ArH) ppm;
13C NMR (CDCl3, 100 MHz) δ = 29.6, 56.0, 64.0, 72.8, 76.6, 81.3, 92.6, 109.5, 110.9, 118.5,
121.3, 121.7, 123.7, 125.5, 126.6, 128.1, 130.5, 139.7, 141.7, 142.1, 148.2, 174.0 ppm; HRMS
(ESI) Calculated for C22H17NO4 (M+Na)+: 382.1053 found: 382.1049.
Synthesis of 5'-bromo-1'-benzyl-7-methoxy-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-
indol]-2'(1'H)-one (4g)
A solution of 1-benzyl-5-bromo-3-diazoindolin-2-one 1e (100 mg,
0.30 mmol) in dry dichloroethane (4 mL) was added dropwise to a
solution containing 4-methoxy-2-(prop-2-yn-1-
yloxy)benzaldehyde 2f (103 mg, 0.33 mmol) dissolved in dry DCE
(5 mL) and copper(I) thiophenecarboxylate (3 mg, 5 mol%) at
reflux conditions to afford 4g (102 mg, 70%) as a white solid
according to general procedure II. Rf = 0.30 (EtOAc/hexane = 1:4, v/v); mp 195-196 °C; IR
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4h
4i
(neat): νmax 2924, 1729, 1644, 1433, 1161, 1030, 809 cm−1; 1H NMR (CDCl3, 400 MHz) δ =
3.80 (s, 3H, CH3), 4.87 (s, 2H, CH2), 4.94 (ABq, ΔδAB = 0.04, J = 12.8 Hz, 2H, CH2), 5.62 (s,
1H, CH), 6.28 (s, 1H, CH), 6.45 (s, 1H, ArH), 6.54-6.59 (m, 2H, ArH), 7.06 (s, 1H, ArH), 7.23-
7.35 (m, 7H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.1, 55.4, 63.7, 81.3, 92.1, 101.7,
108.5, 111.0, 116.1, 117.6, 121.7, 127.3, 127.89, 127.98, 128.7, 129.0, 130.2, 133.2, 134.9,
140.7, 141.7, 153.9, 160.6, 174.7 ppm; HRMS (ESI) Calculated for C26H2079BrNO4 (M+H)
+:
490.0654 found: 490.0648.
Synthesis of 1'-methyl-4H,11cH-spiro[furo[2,3-d]naphtho[2,1-b]pyran-2,3'-indol]-2'(1'H)-
one (4h)
A solution of 3-diazo-1-methylindolin-2-one 1f (100 mg, 0.58 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 2-(prop-2-yn-1-yloxy)-
1-naphthaldehyde 2g (134 mg, 0.64 mmol) dissolved in dry DCE (5 mL)
and copper(I) thiophenecarboxylate (6 mg, 5 mol%) at reflux conditions
to afford 4h (171 mg, 83%) as a white solid according to general
procedure II. Rf = 0.39 (EtOAc/hexane = 1:4, v/v); mp 186-187 °C; IR
(neat): νmax 2254, 1720, 1617, 1466, 1088, 1015, 753 cm−1; 1H NMR
(CDCl3, 400 MHz) δ = 3.23 (s, 3H, CH3), 4.95 (ABq, ΔδAB = 0.13, J = 12 Hz, 2H, CH2), 5.76 (s,
1H, CH), 6.77-6.81 (m, 2H, ArH), 6.87-6.90 (m, 1H, ArH), 6.93-6.95 (m, 1H, ArH), 7.08 (d, J =
9.2 Hz, 1H, ArH), 7.23-7.27 (m, 1H, ArH), 7.31-7.35 (m, 1H, ArH), 7.40-7.44 (m, 1H, ArH),
7.71-7.75 (m, 2H, ArH), 8.21 (d, J = 8.4 Hz, 1H, ArH), ppm; 13C NMR (CDCl3, 100 MHz) δ
26.4, 63.9, 80.29, 92.0, 108.3, 116.8, 118.7, 123.3, 123.8, 123.9, 125.3, 125.6, 126.8, 128.0,
128.2, 129.4, 130.3, 130.4, 132.6, 140.2, 143.7, 151.8, 175.3 ppm; HRMS (ESI) Calculated for
C23H17NO3 (M+H)+: 356.1287 found: 356.1280.
Synthesis of 1'-ethyl-4H,11cH-spiro[furo[2,3-d]naphtho[2,1-b]pyran-2,3'-indol]-2'(1'H)-one
(4i)
A solution of 3-diazo-1-ethylindolin-2-one 1b (100 mg, 0.53 mmol) in
dry dichloroethane (4 mL) was added dropwise to a solution containing
2-(prop-2-yn-1-yloxy)-1-naphthaldehyde 2g (123 mg, 0.58 mmol)
dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (5 mg,
5 mol%) at reflux conditions to afford 4i (158 mg, 81%) as a white solid
according to general procedure II. Rf = 0.44 (EtOAc/hexane = 1:4, v/v);
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S9
4j
mp 174-175 °C; IR (neat): νmax 2976, 1722, 1464, 1360, 1216, 1033, 754 cm−1; 1H NMR (CDCl3,
400 MHz) δ =1.33 (t, J = 7.2, 3H, CH3), 3.78 (q, J = 7.2 Hz, 2H, CH2), 4.95 (ABq, ΔδAB = 0.12, J
= 12 Hz, 2H, CH2), 5.76 (s, 1H, CH), 6.80-6.82 (m, 2H, ArH), 6.85-6.89 (m, 1H, ArH), 6.93-
6.96 (m, 1H, ArH), 7.08 (d, J = 9.2 Hz, 1H, ArH), 7.22-7.26 (m, 1H, ArH), 7.31-7.35 (m, 1H,
ArH), 7.41-7.45 (m, 1H, ArH), 7.71-7.75 (m, 2H, ArH), 8.23 (d, J = 8.4 Hz, 1H, ArH) ppm; 13C
NMR (CDCl3, 100 MHz) δ 12.7, 34.9, 63.8, 80.32, 92.0, 108.5, 116.9, 118.7, 123.0, 123.9,
125.4, 125.7, 126.8, 128.0 128.5, 129.4, 130.24, 130.28, 130.29, 132.6, 140.1, 142.8, 151.8,
174.9 ppm; HRMS (ESI) Calculated for C24H19NO3 (M+Na)+: 370.1443 found: 370.1425.
Crystal data for compound (4i): (CCDC 1580080) C24H19NO3, white colour, diamond, M =
699.64, 0.28 × 0.19 × 0.11 mm, Triclinic, space group P-1 with a = 9.0014(13) Å, b =
9.5478(13) Å, c = 23.864(3) Å, α = 91.650(2) (2)°, β = 95.150(2) (2)°, γ = 113.925(2) (2)°, V =
1862.4(5) Å3, T = 150(2) K, R1 = 0.0465, wR2 = 0.1282 on observed data, z = 2, Dcalcd = 1.317
g/cm3, F(000) = 776, Absorption coefficient = 0.087 mm-1, λ = 0.71073 Å, 6462 reflections were
collected on a smart apex CCD single crystal diffractometer 5683 observed reflections (I≥2σ (I)).
The largest difference peak and hole = 0.249 and -0.226 e.Å-3, respectively. The structure was
solved by direct methods and refined by full-matrix least squares on F2 using SHELXL–97
software.
Synthesis of 1'-benzyl-4H,11cH-spiro[furo[2,3-d][1]naptho[2,1-b]pyran-2,3'-indol]-2'(1'H)-
one (4j)
A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 2-(prop-2-yn-1-yloxy)-1-naphthaldehyde 2g
(92 mg, 0.44 mmol) dissolved in dry DCE (5 mL) and copper(I)
thiophenecarboxylate (4 mg, 5 mol%) at reflux conditions to afford 4j
(131 mg, 76%) as a white solid according to general procedure II. Rf =
0.34 (EtOAc/hexane = 1:4, v/v); mp 189-190 °C; IR (neat): νmax 2933,
1728, 1610, 1475, 1180, 1033, 699 cm−1; 1H NMR (CDCl3, 400 MHz) δ
= 4.74-4.77 (m, 1H, CH), 4.82-4.85 (m, 1H, CH), 4.93-4.98 (m, 2H,
CH2), 5.74 (s, 1H, CH), 6.61 (d, J = 7.6 Hz, 1H, CH), 6.77-6.80 (m, 2H, ArH), 6.88 (d, J = 6.8
Hz, 1H, ArH), 7.01-7.08 (m, 2H, ArH), 7.18-7.29 (m, 6H, ArH), 7.36-7.40 (m, 1H, ArH), 7.65-
7.69 (m, 2H, ArH), 8.18 (d, J = 8.4 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz ) δ 44.1,
63.8, 80.4, 92.0, 109.3, 116.7, 118.7, 123.3, 123.9, 124.0, 125.4, 125.6, 126.7, 127.5, 127.8,
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4k
4l
128.0, 128.3, 128.9, 129.4, 130.26, 130.3, 132.6, 135.5, 140.3, 142.8, 151.8, 175.5 ppm ; HRMS
(ESI) Calculated for C29H21NO3 (M+H)+: 432.1600 found: 432.1595.
Synthesis of 1'-benzyl-6,8-diiodo-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-
2'(1'H)-one (4k)
A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 3,5-diiodo-2-(prop-2-yn-1-yloxy)benzaldehyde
2h (180 mg, 0.44 mmol) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (4
mg, 5 mol%) at reflux conditions to afford 4k (189 mg, 75%) as a white solid according to
general procedure II. Rf = 0.09 (EtOAc/hexane = 1.5:3.5, v/v); mp 215-216 °C; IR (neat): νmax
2923, 1728, 1611, 1484, 1432, 1161, 667 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.94 (s, 2H,
CH2), 5.14 (ABq, ΔδAB = 0.05, J = 13.2 Hz, 2H, CH2), 5.72 (s, 1H, CH),
6.27 (s, 1H, CH), 6.76 (d, J = 8 Hz, 1H, ArH), 6.99-7.05 (m, 2H, ArH),
7.24-7.41 (m, 6H, ArH), 7.67 (s, 1H, ArH), 8.04 (s, 1H, ArH) ppm ; 13C
NMR (CDCl3, 100 MHz ) δ = 44.1, 64.6, 80.5, 84.1, 86.2, 93.0, 109.6,
122.9, 123.5, 125.5, 127.4, 127.6, 127.9, 128.3, 129.0, 130.7, 135.3, 135.5,
138.4, 142.8, 146.2, 151.8, 174.6 ppm; HRMS (ESI) Calculated for
C25H17I2NO3 (M+Na)+: 655.9196 found: 655.9193.
Synthesis of 5'-chloro-1'-benzyl-7,9-diiodo-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-
indol]-2'(1'H)-one (4l)
A solution of 1-benzyl-5-chloro-3-diazoindolin-2-one 1g (100 mg, 0.35 mmol) in dry
dichloroethane (4 mL) was added dropwise to a solution containing 3,5-diiodo-2-(prop-2-yn-1-
yloxy)benzaldehyde 2h (160 mg, 0.39 mmol) dissolved in dry DCE (5
mL) and copper(I) thiophenecarboxylate (4 mg, 5 mol%) at reflux
conditions to afford (189 mg, 81%) of 4l as a white solid according to
general procedure II. Rf = 0.48 (EtOAc/hexane = 1.5:3.5, v/v); mp 229-
230 °C; IR (neat): νmax 2933, 1724, 1614, 1500, 1159, 1022, 754 cm−1;
1H NMR (CDCl3, 400 MHz) δ = 4.88 (ABq, ΔδAB = 0.02, J = 16 Hz,
2H, CH2), 5.08 (ABq, ΔδAB = 0.06, J = 13.6 Hz, 2H, CH2), 5.67 (s, 1H, CH), 6.23 (s, 1H, CH),
6.62 (d, J = 8.4 Hz, 1H, ArH), 6.95 (s, 1H, ArH), 7.17 (d, J = 8.4 Hz, 1H, ArH), 7.27-7.34 (m,
5H, ArH), 7.61 (s, 1H, ArH), 8.00 (s, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.2,
64.5, 80.6, 84.3, 86.3, 92.6, 110.7, 122.3, 126.0, 127.3, 127.8, 128.0, 129.00, 129.04, 129.1,
-
S11
4m
4n
130.6, 134.8, 135.5, 139.1, 141.3, 146.4, 151.7, 174.2 ppm; HRMS (ESI) Calculated for
C25H1635ClI2NO3 (M+H)
+: 667.8986 found: 667.8979.
Synthesis of 3-benzyl-1'-methyl-4H,11cH-spiro[furo[2,3-d]naphtho[2,1-b]pyran-2,3'-indol]-
2'(1'H)-one (4m)
A solution of 3-diazo-1-methylindolin-2-one 1f (100 mg, 0.58 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 2-((3-phenylprop-2-yn-1-yl)oxy)-1-
naphthaldehyde 2i (183 mg, 0.64 mmol) dissolved in dry DCE (5 mL)
and copper(I) thiophenecarboxylate (6 mg, 5 mol%) at reflux
conditions to afford (210 mg, 84%) of 4m as a white solid according to
general procedure II. Rf = 0.25 (EtOAc/hexane = 1.5:3.5, v/v); mp 230-
231 °C; IR (neat): νmax 2923, 1728, 1611, 1433, 1341, 1166, 737 cm−1;
1H NMR (CDCl3, 400 MHz) δ = 3.08 (s, 3H, CH3), 4.93 (ABq, ΔδAB =
0.07, J = 12.1 Hz, 2H, CH2), 6.62 (d, J = 8 Hz, 1H, CH), 6.80-6.84 (m, 1H, ArH), 6.90-6.96 (m,
4H, ArH), 7.08 (d, J = 8.8 Hz, 1H, ArH), 7.13-7.21 (m, 4H, ArH), 7.29-7.33 (m, 1H, ArH), 7.39-
7.43 (m, 1H, ArH), 7.69-7.74 (m, 2H, ArH), 8.26 (d, J = 8.4 Hz, 1H, ArH) ppm; 13C NMR
(CDCl3, 100 MHz) δ = 26.4, 63.1, 80.5, 94.4, 108.4, 117.2, 118.8, 123.3, 123.9, 125.5, 125.8,
126.8, 128.0, 128.04, 128.4, 128.6, 128.7, 129.4, 130.3, 130.4, 130.9, 132.7, 135.1, 136.5, 144.1,
152.0, 175.3 ppm; HRMS (ESI) Calculated for C29H21NO3 (M+Na)+: 454.1419 found: 454.1409.
Synthesis of 5'-bromo-3-(4-nitrophenyl)-1'-benzyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-
2,3'-indol]-2'(1'H)-one (4n)
A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 2-((3-(4-nitrophenyl)prop-2-yn-1-
yl)oxy)benzaldehyde 2j (124 mg, 0.44 mmol) dissolved in dry DCE
(5 mL) and copper(I) thiophenecarboxylate (4 mg, 5 mol%) at reflux
conditions to afford (163 mg, 81%) of 4n as a white solid according
to general procedure II. Rf = 0.44 (EtOAc/hexane = 1.5:3.5, v/v); mp
248-249 °C IR (neat): νmax 2923, 1705, 1601, 1457, 1335, 1166, 744
cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.57 (d, 1H, J = 15.6 Hz,
CH), 4.86 (d, J = 13.6 Hz, 1H, CH), 5.01-5.09 (m, 2H, CH2), 6.45 (s, 1H, OCH), 6.67 (d, 1H, J =
7.6 Hz, ArH), 6.91-7.05 (m, 8H, ArH), 7.13-7.29 (m, 4H, ArH), 7.43 (d, J = 7.6 Hz, 1H, ArH),
7.96 (d, J = 9.2 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 43.9, 62.8, 81.8, 94.7,
-
S12
4o
4p
109.7, 116.8, 121.8, 123.7, 123.74, 125.6, 126.0, 126.6, 127.2, 127.4, 127.9, 128.7, 129.38,
129.44, 131.0, 132.7, 135.0, 137.3, 137.6, 142.9, 147.8, 152.7, 174.5 ppm; HRMS (ESI)
Calculated for C29H21NO3 (M+Na)+: 525.1426 found: 525.1427.
Synthesis of 3-(4-nitrophenyl)-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-
one (4o)
A solution of 3-diazoindolin-2-one 1h (100 mg, 0.63 mmol) in dry dichloroethane (4 mL) was
added dropwise to a solution containing 2-((3-(4-nitrophenyl)prop-2-yn-1-yl)oxy)benzaldehyde
2j (195 mg, 0.69 mmol) dissolved in dry DCE (5 mL) and copper(I)
thiophenecarboxylate (6 mg, 5 mol%) at reflux conditions to afford
(203 mg, 78%) of 4o as a white solid according to general procedure
II. Rf = 0.76 (EtOAc/hexane = 2:3, v/v); mp 230-231 °C; IR (neat):
νmax 3004, 2253, 1441, 1377, 1039, 918, 743 cm−1; 1H NMR (CDCl3,
400 MHz) δ = 4.94 (ABq, ΔδAB = 0.18, J = 13.4 Hz, 2H, CH2 6.38 (s,
1H, CH), 6.82 (d, J = 7.6 Hz, 1H, ArH), 6.91-7.06 (m, 5H, ArH), 7.23-7.28 (m, 3H, ArH), 7.40
(d, J = 7.6 Hz, 1H, ArH), 8.05 (d, J = 8.8 Hz, 2H, ArH), 8.27 (br s, 1H, NH) ppm; 13C NMR
(CDCl3, 100 MHz) δ = 62.9, 81.8, 94.8, 110.7, 116.9, 121.8, 123.8, 123.9, 125.9, 126.0, 126.5,
127.9, 129.1, 129.5, 131.1, 132.2, 137.4, 138.1, 140.9, 147.8, 152.6, 176.6 ppm; HRMS (ESI)
Calculated for C24H16N2O5 (M-H)+: 411.0986 found: 411.0976.
Synthesis of 1'-benzyl-3-(4-iodophenyl)-4H,11cH-spiro[furo[2,3-d]naphtho[2,1-b]pyran-
2,3'-indol]-2'(1'H)-one (4p)
A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 2-((3-(4-iodophenyl)prop-2-yn-1-yl)oxy)-1-
naphthaldehyde 2k (181 mg, 0.44 mmol) dissolved in dry DCE (5
mL) and copper(I) thiophenecarboxylate (4 mg, 5 mol%) at reflux
conditions to afford (210 mg, 83%) of 4p as a white solid according
to general procedure II. Rf = 0.41 (EtOAc/hexane = 1.5:3.5, v/v);
mp 245-246 °C; IR (neat): νmax 2924, 1722, 1613, 1469, 1353, 1216,
952, 753 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.43 (d, J = 16 Hz,
1H, CH2), 4.92 (ABq, ΔδAB = 0.02, J = 12.2 Hz, 2H, CH2), 5.16 (d, J = 15.7, 1H, CH2), 6.52-6.57
(m, 3H, ArH), 6.82-6.87 (m, 3H, ArH), 6.96-7.00 (m, 2H, ArH), 7.07-7.11 (m, 2H, ArH), 7.17-
7.24 (m, 3H, ArH), 7.33-7.37 (m, 1H, ArH), 7.44-7.50 (m, 3H, ArH), 7.72-7.77 (m, 2H, ArH),
-
S13
4q
8.29 (d, J = 8.4 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 43.7, 62.9, 80.8, 94.6, 95.2,
109.6, 117.0, 118.7, 123.4, 124.0, 125.4, 125.7, 126.8, 126.9, 127.6, 127.7, 128.1, 128.8, 129.4,
130.1, 130.4, 130.6, 132.6, 135.0, 135.4, 135.9, 137.8, 143.0, 151.8, 175.2 ppm; HRMS (ESI)
Calculated for C35H24INO3 (M+H)+: 634.0879 found: 634.0874.
Synthesis of 1'-benzyl-3-(6-bromopyridin-2-yl)-7-methoxy-4H,9bH-spiro[furo[3,2-
c][1]benzopyran-2,3'-indol]-2'(1'H)-one (4q)
A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 2-((3-(6-bromopyridin-2-yl)prop-2-yn-1-
yl)oxy)-4-methoxybenzaldehyde 2l (152 mg, 0.44 mmol) dissolved in
dry DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg, 5 mol%)
at reflux conditions to afford (186 mg, 82%) of 4q as a white solid
according to general procedure II. Rf = 0.40 (EtOAc/hexane = 1.5:3.5,
v/v); mp 226-227 °C; IR (neat): νmax 2924, 1725, 1611, 1436, 1259,
1159, 1116, 1029, 748 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.80 (s,
3H CH3), 4.98 (ABq, ΔδAB = 0.10, J = 15.6 Hz, 2H, CH2), 5.25-5.29 (m, 1H, CH2), 5.66 (d, J =
15.2 Hz, 1H, CH2), 6.35 (s, 1H, CH), 6.51-6.61 (m, 3H, ArH), 6.79-6.81 (m, 1H, ArH), 6.87-6.94
(m, 2H, ArH), 7.12-7. 37 (m, 9H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.3, 55.5, 65.4,
81.5, 92.7, 102.2, 108.5, 109.6, 119.7, 119.8, 123.5, 125.4, 126.2, 126.7, 127.75, 127.8, 128.4,
128.9, 129.0, 130.6, 135.7, 138.6, 141.5, 143.0, 143.5, 151.1, 154.0, 160.4, 174.9 ppm; HRMS
(ESI) Calculated for C31H2379BrN2O4 (M+Na)
+: 589.0739 found: 589.0724.
Procedure for the synthesis of compound 5
Synthesis of 2,2'-((1,4-phenylenebis(prop-2-yne-3,1-diyl))bis(oxy))dibenzaldehyde (5)
To a mixture of compound 2a (1 g, 6.24 mmol), 1,4-diiodobene (1.029 g, 3.12 mmol) in dry
triethylamine / dichloromethane (4:1) (5 mL) under a nitrogen atmosphere were added
[Pd(PPh3)2Cl2] (175 mg, 0.25 mmol) and CuI (24 mg, 0.12 mmol) successively. The reaction
mixture was stirred at room temperature for 6 h. After that, the solvent was removed under
reduced pressure, added water and extracted with dichloromethane. The crude product was
-
S14
6
5
purified by column chromatography using silica gel to afford the bis-aldehyde derivative (1.4 g,
58%) of 5 as a white solid. Rf = 0.19 (EtOAc/hexane = 1:4, v/v); mp 153-154 °C; IR (neat): νmax
2861, 1681, 1594, 1455, 1212, 1007, 834, cm−1; 1H NMR (CDCl3, 400 MHz) δ = 5.05 (s, 2H,
CH2), 7.09 (t, J = 7.6 Hz, 1H, ArH), 7.17 (d, J = 8.4 Hz, 1H, ArH), 7.36 (s, 2H, ArH), 7.56-7.60
(m, 1H, ArH), 7.87 (dd, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H, ArH) 10.52 (s, 1H, CH) ppm; 13C NMR
(CDCl3, 100 MHz) δ = 57.25, 85.03, 87.41, 113.39, 121.69, 122.43, 125.59, 128.65, 131.74,
135.77, 159.98, 189.65 ppm; HRMS (ESI) Calculated for
C26H18O4 (M+Na)+: 417.1103 found: 417.1098.
Synthesis of 1'-methyl-3-[4-(1'-methyl-2'-oxo-1',2',3'a,7'a-
tetrahydro-4H,9bH-spiro[furo [3,2-c][1]benzopyran-2,3'-indol]-3-
yl)phenyl]9a,9bdihydro4H,5aHspiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-one (6)
A solution of 1-methyl-3-diazoindolin-2-one 1f (100 mg, 0.58 mmol) in dry dichloroethane (4
mL) was added dropwise to a solution containing 2,2'-((1,4-phenylenebis(prop-2-yne-3,1-
diyl))bis(oxy))dibenzaldehyde 5 (115 mg, 0.029 mmol)
dissolved in dry DCE (5 mL) and copper(I)
thiophenecarboxylate (6 mg, 5 mol%) at reflux conditions to
afford 6 (157 mg, 79%) as a white solid according to general
procedure II. Rf = 0.06 (EtOAc/hexane = 1.5:3.5, v/v); mp
231-232 °C; IR (neat): νmax 2923, 1716, 1608, 1471, 1215,
1109, 755 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.09 (s, 3H,
CH3), 4.79-4.84 (m, 1H, CH2), 4.94-5.00 (m, 1H, CH2), 6.31 (s, 1H, CH), 6.57 (s, 1H, CH), 6.23
(s, 1H, CH), 6.74 (t, J = 8.4 Hz, 1H, ArH), 6.85-6.91 (m, 2H, ArH), 6.93-6.99 (m, 2H, ArH),
7.20-7.35 (m, 3H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 26.5, 63.2, 81.2, 94.3, 108.7,
116.7, 121.5, 123.5, 125.6, 126.4, 126.5, 126.6, 128.2, 128.3, 129.2, 130.7, 131.1, 133.5, 135.5,
144.0, 152.7, 174.8 ppm (due to the C2 Symmetry we observed half-half the signal); HRMS
(ESI) Calculated for C44H32N2O6 (M+Na)+: 685.2339 found: 685.2337.
Synthesis of dimethyl 1'-benzyl-2'-oxo-5-(2-(prop-2-yn-1-yloxy)phenyl)-5H-spiro[furan-
2,3'-indoline]-3,4-dicarboxylate (7)
To a mixture of spiro-indolooxirane 3a (100 mg, 0.26 mmol) and dimethyl
acetylenedicarboxylate (41 mg, 0.29 mmol) in dry toluene (5 mL) was stirred at reflux conditions
for 32 hours to afford 7 (90 mg, 66%) as a colorless liquid. Rf = 0.13 (EtOAc/hexane = 1:4, v/v);
-
S15
8
7
IR (neat): νmax 3282, 2952, 2123(w), 1723, 1611, 1259, 1022, 754. cm−1;
1H NMR (CDCl3, 400 MHz) δ = 2.52 (s, 1H, ≡CH), 3.48 (s, 3H, CH3),
3.75 (s, 3H, CH3), 4.63-4.74 (m, 3H, CH2), 5.07 (d, J = 16 Hz, 1H, CH2),
6.68 (d, J = 7.6 Hz, 1H, CH), 6.91 (s, 1H, ArH), 7.00-7.07 (m, 3H,
ArH), 7.18-7.42 (m, 8H, ArH), 7.56 (d, J = 7.2 Hz, 1H, ArH) ppm; 13C
NMR (CDCl3, 100 MHz) δ = 44.1, 52.4, 52.7, 56.1, 76.02, 78.4, 83.7,
89.5, 109.6, 112.1, 121.8, 123.2, 125.3, 126.2, 127.3, 127.4, 127.7,
128.2, 128.8, 130.1, 130.9, 135.5, 143.8, 147.3, 155.1, 161.0, 163.1, 173.8 2 ppm; HRMS (ESI)
Calculated for C31H25NO7 (M+H)+: 524.1709 found: 524.1712.
Synthesis of 1'-ethyl-5-phenyl-3-(2-(prop-2-yn-1-yloxy)phenyl)-3a,6a-dihydrospiro[furo
[3,4-c]pyrrole-1,3'-indoline]-2',4,6(3H,5H)-trione (8)
To a mixture of spiro-indolooxirane 3a (100 mg, 0.26 mmol) and N-phenylmaleimide (50 mg,
0.30 mmol) in dry toluene (5 mL) was stirred at reflux conditions for
27 hours to afford 8 (94 mg, 65%) as a white solid. Rf = 0.13
(EtOAc/hexane = 1:4, v/v); mp 186-187 °C; IR (neat): νmax 3289,
2923, 2125(w), 1714, 1614, 1339, 1267, 1006, 734 cm−1; 1H NMR
(CDCl3, 400 MHz) δ = 2.55 (t, J = 2.4 Hz, 1H, ≡CH), 3.87 (d, J = 8
Hz, 1H, CH), 4.45 (t, J = 8.1 Hz, 1H, CH), 4.83-4.87 (m, 3H, CH2),
4.98 (d, J = 15.6 Hz, 1H, CH2), 6.54 (d, J = 8 Hz, 1H, ArH), 6.78 (d, J
= 8 Hz, 1H, ArH), 6.99-7.12 (m, 5H, ArH), 7.24-7.41 (m, 11H, ArH), 7.47 (d, J = 7.6 Hz, 1H,
ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 43.8, 49.5, 52.0, 56.4, 75.7, 78.7, 83.9, 109.8,
111.6, 121.3, 123.1, 123.4, 125.1, 125.5, 126.1, 126.7, 127.3, 127.9, 128.6, 129.0, 129.2, 131.0,
131.6, 135.1, 143.4, 154.9, 172.9, 173.1, 175.8 ppm; HRMS (ESI) Calculated for C31H26N2O5
(M+Na)+: 577.1739 found: 577.1734.
Synthesis of dimethyl 1'-ethyl-2'-oxo-5-(2-(prop-2-yn-1-yloxy)phenyl)-5H-spiro[furan-2,3'-
indoline]-3,4-dicarboxylate (9)
A solution of 3-diazo-1-ethylindolin-2-one 1b (100 mg, 0.53 mmol) in dry dichloroethane or
toluene (4 mL) was added dropwise to a mixture of solution containing 2-[(prop-2-yn-1-
yl)oxy]benzaldehyde 2a (93 mg, 0.58 mmol), dimethyl acetylenedicarboxylate (83 mg, 0.58
mmol) and copper(I) thiophenecarboxylate (5 mg, 5 mol%) at reflux conditions for 1 hour to
afford 9 (164 mg, 67%) as a colorless liquid. Rf = 0.09 (EtOAc/hexane = 1:4, v/v); IR (neat): νmax
-
S16
9
3281, 2923, 2123, 1720, 1610, 1257, 1018, 742 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 1.33 (t, J
= 7.2 Hz, 3H, CH3), 2.57 (t, J = 2.4 Hz, 1H, ≡CH), 3.60 (s, 3H, CH3), 3.71-3.78 (m, 1H, CH),
3.81 (s, 3H, CH3), 3.84-3.93 (m, 1H, CH), 4.72 (ABqd, ΔδAB = 0.06, J1 =
15.8 Hz, J2 = 2.3 Hz, 2H, CH2), 6.88-6.91 (m, 2H, ArH), 7.07-7.13 (m,
3H, ArH), 7.37-7.45 (m, 3H, ArH), 7.58-7.60 (m, 1H, ArH) ppm; 13C
NMR (CDCl3, 100 MHz) δ = 12.3, 34.9, 52.3, 52.6, 56.1, 75.9, 78.4,
83.7, 89.5, 108.5, 112.1, 121.8, 122.9, 125.4, 126.3, 127.5, 128.2, 130.1,
130.8, 132.1, 143.7, 146.8, 155.1, 160.9, 163.1, 173.2 ppm; HRMS (ESI)
Calculated for C26H23NO7 (M+Na)+: 484.1372 found: 484.1377.
-
S17
Copies of 1H and 13C NMR spectra
1H NMR spectrum of 3a
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.57
7
2.40
1
2.40
7
2.41
2
4.57
0
4.57
5
4.60
9
4.61
5
4.62
5
4.63
0
4.66
5
4.67
0
4.80
5
4.82
9
4.84
5
4.84
9
4.88
9
6.76
4
6.78
4
6.99
2
7.01
3
7.06
7
7.08
6
7.10
5
7.12
8
7.14
7
7.23
8
7.24
8
7.26
0
7.26
6
7.27
5
7.28
9
7.29
3
7.31
1
7.33
1
7.33
4
7.35
1
7.37
0
1.00
2.27
3.34
1.07
1.06
2.22
7.31
1.23
1.06
apr-25 bn PROTON CDCl3 17/8/2018
3a
-
S18
13C NMR spectrum of 3a
200 180 160 140 120 100 80 60 40 20 0 ppm
44
.04
55
.95
61
.49
63
.98
75
.69
76
.73
77
.04
77
.36
78
.37
10
9.5
7
11
1.5
0
12
1.0
6
12
1.5
7
12
1.9
3
12
2.6
4
12
3.7
1
12
7.4
1
12
7.6
5
12
8.7
7
12
9.0
2
12
9.6
2
12
9.9
4
13
5.6
2
14
3.8
3
15
5.4
5
17
0.2
7
3a
-
S19
1H NMR spectrum of 3b
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.2
06
1.2
24
1.2
42
1.5
88
2.4
10
2.4
16
2.4
22
3.6
58
3.6
76
3.6
94
3.7
07
3.7
12
3.7
25
3.7
43
3.7
61
4.5
90
4.5
95
4.6
01
4.7
39
6.8
99
6.9
10
6.9
21
6.9
30
7.0
93
7.1
12
7.1
30
7.1
31
7.2
33
7.2
51
7.2
60
7.2
66
7.2
81
7.2
88
7.3
69
7.3
72
7.3
88
7.3
91
7.4
07
7.4
10
7.7
42
3.3
0
1.0
0
2.3
0
1.9
8
1.0
1
2.1
4
1.1
0
2.2
8
1.1
1
0.9
9
apr-54a PROTON CDCl3 14/09/2016
3b
-
S20
13C NMR spectrum of 3b
3b
-
S21
1H NMR spectrum of 3e
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.58
1
2.50
8
2.51
4
2.52
0
4.72
6
4.73
1
4.73
6
4.79
3
4.82
9
4.84
8
4.88
7
6.79
4
6.81
3
7.08
4
7.08
9
7.09
0
7.10
7
7.12
7
7.12
8
7.22
9
7.24
8
7.25
4
7.25
8
7.27
4
7.28
0
7.29
2
7.29
7
7.30
0
7.31
0
7.31
4
7.31
9
7.32
2
8.24
4
8.25
1
1.00
1.95
3.23
1.09
2.23
8.18
1.08
0.97
apr 58 PROTON CDCl3 4/10/2016
3e
-
S22
13C NMR spectrum of 3e
200 180 160 140 120 100 80 60 40 20 0 ppm
44
.09
56
.55
61
.36
62
.51
76
.75
77
.07
77
.39
10
9.8
4
11
1.3
9
12
2.1
4
12
2.8
2
12
2.9
1
12
5.4
9
12
5.6
9
12
7.3
4
12
7.8
0
12
8.8
6
13
0.4
6
13
5.3
3
14
1.8
0
14
3.9
3
15
9.7
5
16
9.7
2
3e
-
S23
1H NMR spectrum of 4a
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.63
1
4.85
4
4.89
3
4.91
1
4.95
0
4.97
9
5.62
2
6.30
0
6.68
6
6.70
6
6.89
2
6.91
1
6.92
4
6.95
6
6.97
5
6.99
3
7.15
3
7.16
2
7.16
8
7.17
4
7.18
1
7.18
7
7.19
5
7.20
7
7.22
7
7.25
4
7.27
3
7.28
4
7.29
4
7.30
5
7.32
7
2.00
2.34
1.14
1.32
1.12
4.34
4.09
3.96
apr-25 bn PROTON CDCl3 16/08/2018
4.854.904.955.005.05 ppm
4.85
4
4.89
3
4.91
1
4.95
0
4.97
9
4a
-
S24
13C NMR spectrum of 4a
200 180 160 140 120 100 80 60 40 20 0 ppm
44
.06
63
.70
76
.75
77
.06
77
.38
81
.39
92
.66
10
9.4
5
11
6.7
7
12
1.4
6
12
1.8
3
12
3.3
7
12
5.4
9
12
5.9
9
12
6.8
3
12
7.4
0
12
7.8
0
12
8.3
1
12
8.9
0
12
9.1
8
13
0.3
8
13
5.4
2
13
9.8
7
14
2.6
8
15
2.7
8
17
5.2
2
4a
-
S25
1H NMR spectrum of 4b
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.28
5
1.30
3
1.32
1
1.57
8
3.68
4
3.70
1
3.71
9
3.73
7
3.75
0
3.75
5
3.76
7
3.77
2
3.78
5
3.80
3
3.82
1
3.83
9
4.96
2
5.59
4
6.18
9
6.82
1
6.83
7
6.84
3
6.85
7
6.92
0
6.93
6
6.93
9
6.97
2
6.99
1
7.01
0
7.15
2
7.15
9
7.17
4
7.18
1
7.26
2
7.29
4
7.29
8
7.31
5
7.31
7
7.32
1
7.33
3
3.13
2.23
2.00
1.00
0.98
1.96
0.94
1.03
0.98
2.07
apr-54 c PROTON CDCl3 16/9/2016
4b
-
S26
13C NMR spectrum of 4b
200 180 160 140 120 100 80 60 40 20 0 ppm
12
.60
35
.02
63
.81
76
.74
77
.05
77
.37
80
.77
92
.74
10
8.6
3
11
8.2
3
12
2.3
8
12
3.2
0
12
5.5
8
12
6.2
8
12
6.4
2
12
7.3
6
12
8.1
5
12
9.1
7
13
0.6
0
13
8.8
4
14
2.7
2
15
1.3
5
17
4.3
6
4b
-
S27
1H NMR spectrum of 4c
9 8 7 6 5 4 3 2 1 0 ppm
4.90
9
4.95
0
4.98
9
5.02
2
5.05
6
5.69
0
6.27
5
6.74
7
6.76
6
6.87
6
6.89
8
6.97
4
6.98
9
7.00
7
7.02
5
7.20
4
7.20
9
7.22
6
7.24
4
7.26
1
7.30
3
7.32
4
7.33
6
7.34
4
7.37
4
7.38
6
2.02
2.09
1.00
1.00
1.03
1.01
2.06
2.13
6.31
apr-88 PROTON CDCl3 22/02/2017
4c
-
S28
13C NMR spectrum of 4c
200 180 160 140 120 100 80 60 40 20 0 ppm
44
.07
63
.82
76
.76
77
.07
77
.39
80
.86
92
.76
10
9.5
5
11
8.2
8
12
2.3
5
12
3.4
6
12
5.4
8
12
6.3
3
12
6.4
7
12
7.3
1
12
7.3
8
12
7.8
4
12
7.9
4
12
8.9
3
12
9.2
3
13
0.5
6
13
5.3
3
13
9.0
8
14
2.7
2
15
1.3
7
17
4.9
4
1
4c
-
S29
H NMR spectrum of 4d
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
0.9
73
0.9
92
1.0
10
1.2
52
1.6
59
1.6
92
1.7
11
1.7
29
1.7
47
1.7
66
1.7
84
3.6
49
3.6
67
3.6
86
4.9
25
4.9
62
4.9
96
5.5
99
6.1
93
6.7
71
6.7
93
6.8
29
6.8
49
6.9
22
6.9
40
6.9
73
6.9
91
7.0
10
7.2
65
7.2
92
7.2
98
7.3
09
7.3
12
7.3
20
7.3
27
7.4
60
3.3
2
2.1
9
2.1
7
2.0
0
1.0
2
1.0
2
1.0
2
1.0
8
1.0
4
1.1
2
2.3
7
1.0
1
apr-106 b PROTON CDCl3 5/6/2017
4d
-
S30
13C NMR spectrum of 4d
200 180 160 140 120 100 80 60 40 20 0 ppm
11
.40
20
.66
29
.72
41
.85
63
.82
80
.68
92
.72
10
8.7
9
11
3.5
4
11
8.6
9
12
2.5
2
12
3.1
8
12
5.5
5
12
7.8
3
12
8.0
4
12
9.4
1
13
0.5
7
13
2.0
7
13
8.7
6
14
3.1
1
15
1.8
9
17
4.7
4
4d
-
S31
1H NMR spectrum of 4e
9 8 7 6 5 4 3 2 1 0 ppm
1.6
29
4.9
58
5.1
14
5.1
47
5.1
64
5.1
97
5.7
78
6.3
07
6.7
56
6.7
76
6.9
07
6.9
26
6.9
71
6.9
89
7.0
08
7.0
21
7.0
44
7.2
34
7.2
53
7.2
72
7.3
03
7.3
33
7.3
40
7.3
54
7.3
61
7.3
80
7.3
96
7.4
17
8.1
58
8.1
65
2.0
0
2.0
6
1.0
6
1.0
6
1.0
4
1.0
2
2.1
3
1.0
5
5.3
6
1.0
8
1.0
3
apr-58 b PROTON CDCl3 1/3/2017
4e
-
S32
13C NMR spectrum of 4e
200 180 160 140 120 100 80 60 40 20 0 ppm
-0.0
0
44
.11
64
.53
76
.70
77
.02
77
.34
80
.09
92
.93
10
9.6
6
11
7.5
9
12
3.4
2
12
3.4
6
12
3.5
5
12
5.1
1
12
5.3
4
12
6.2
2
12
7.3
3
12
7.8
7
12
8.9
5
13
0.7
4
13
5.2
3
13
7.4
6
14
2.0
2
14
2.8
1
15
7.9
5
17
4.5
5
4e
-
S33
1H NMR spectrum of 4f
9 8 7 6 5 4 3 2 1 0 ppm
-0.000
1.702
2.268
3.902
4.398
4.402
4.442
4.446
4.532
4.536
4.576
4.581
4.985
5.018
5.070
5.103
5.597
6.257
6.839
6.857
6.917
6.930
6.933
6.947
6.973
6.992
7.011
7.027
7.046
7.266
7.302
7.321
7.341
0.9
0
3.0
0
1.9
7
1.9
8
0.9
2
0.8
6
5.9
2
1.1
8
4f
-
S34
13C NMR spectrum of 4f
200 180 160 140 120 100 80 60 40 20 0 ppm
29
.56
56
.00
64
.04
72
.78
76
.78
77
.10
77
.42
81
.28
92
.55
10
9.5
0
11
0.9
0
11
8.4
5
12
1.2
8
12
1.7
0
12
3.7
0
12
5.5
4
12
6.5
5
12
8.0
8
13
0.4
7
13
9.6
7
14
1.6
8
14
2.0
6
14
8.2
2
17
4.0
4
4f
-
S35
1H NMR spectrum of 4g
9 8 7 6 5 4 3 2 1 0 ppm
1.6
33
3.7
95
4.8
72
4.8
93
4.9
25
4.9
46
4.9
78
5.6
17
6.2
75
6.4
51
6.5
43
6.5
65
6.5
72
6.5
88
6.5
94
7.0
61
7.2
33
7.2
55
7.2
77
7.2
95
7.3
15
7.3
31
7.3
51
3.0
0
2.1
9
1.8
5
1.0
0
1.0
0
1.0
1
2.0
6
0.9
8
7.4
2
apr-117 PROTON CDCl3 4/9/2017
4g
-
S36
13C NMR spectrum of 4g
200 180 160 140 120 100 80 60 40 20 0 ppm
44
.10
55
.40
63
.68
76
.76
77
.08
77
.39
81
.34
92
.13
10
1.6
6
10
8.4
6
11
1.0
1
11
6.1
1
11
7.6
4
12
1.7
2
12
7.3
2
12
7.8
9
12
7.9
8
12
8.6
7
12
9.0
0
13
0.2
2
13
3.2
2
13
4.9
1
14
0.7
0
14
1.7
3
15
3.9
3
16
0.6
2
17
4.7
2
4g
-
S37
1H NMR spectrum of 4h
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.6
54
3.2
25
4.8
68
4.8
98
4.9
97
5.0
27
5.7
56
6.7
69
6.7
89
6.8
07
6.8
13
6.8
67
6.8
86
6.9
04
6.9
33
6.9
36
6.9
51
6.9
54
7.0
73
7.0
96
7.2
27
7.2
30
7.2
46
7.2
50
7.2
65
7.2
69
7.3
06
7.3
08
7.3
26
7.3
43
7.3
46
7.4
01
7.4
04
7.4
22
3.0
0
0.9
7
0.9
5
0.9
4
1.9
4
0.9
5
0.9
4
0.9
4
1.2
1
0.9
7
0.9
9
1.9
6
0.9
6
apr-168 PROTON CDCl3 5/1/2019
4h
-
S38
13C NMR spectrum of 4h
200 180 160 140 120 100 80 60 40 20 0 ppm
26
.42
63
.86
76
.76
77
.08
77
.40
80
.29
91
.97
10
8.3
2
11
6.7
8
11
8.6
6
12
3.2
6
12
3.8
1
12
3.9
4
12
5.3
3
12
5.5
6
12
6.8
1
12
7.9
9
12
8.2
2
12
9.3
8
13
0.2
7
13
0.3
8
13
2.6
1
14
0.2
4
14
3.6
7
15
1.8
2
17
5.3
2
4h
-
S39
1H NMR spectrum of 4i
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
04
1.30
9
1.32
7
1.34
5
1.56
4
3.75
0
3.76
8
3.78
6
3.80
4
4.86
9
4.89
9
4.99
5
5.02
5
5.75
9
6.79
7
6.80
6
6.81
5
6.85
4
6.85
6
6.87
3
6.87
4
6.89
2
6.89
3
6.93
4
6.93
7
6.95
2
6.95
5
7.07
2
7.09
5
7.21
7
7.22
0
7.23
6
7.24
0
7.25
3
7.25
9
7.30
9
7.32
9
7.34
6
7.34
9
7.41
0
7.41
2
7.43
0
7.44
8
7.70
6
7.72
9
7.74
9
8.22
2
8.24
3
3.05
2.09
1.03
1.05
1.00
1.98
1.05
0.99
1.01
1.08
1.03
1.05
2.08
1.04
apr-53 PROTON CDCl3 14/09/2016
4i
-
S40
13C NMR spectrum of 4i
200 180 160 140 120 100 80 60 40 20 0 ppm
12
.70
34
.98
63
.84
76
.77
77
.08
77
.40
80
.32
92
.03
10
8.4
5
11
6.8
5
11
8.6
5
12
3.0
3
12
3.9
3
12
5.3
8
12
5.7
4
12
6.8
1
12
7.9
7
12
8.4
7
12
9.3
8
13
0.2
4
13
0.2
9
13
2.6
2
14
0.0
9
14
2.7
6
15
1.8
0
17
4.9
2
4i
-
S41
COSY spectrum of 4i
ppm
1.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5 ppm
2
3
4
5
6
7
8
apr-53 COSYGPSW CDCl3
4i
-
S42
HSQC spectrum of 4i
ppm
1.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5 ppm
140
120
100
80
60
40
20
0
apr-53 HSQCGP CDCl3
4i
-
S43
1H NMR spectrum of 4j
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.18
2
1.57
1
4.73
6
4.77
4
4.81
9
4.84
8
4.93
3
4.94
6
4.97
2
4.97
5
5.74
1
6.60
3
6.62
2
6.76
5
6.78
3
6.80
2
6.87
6
6.89
3
7.01
0
7.03
2
7.04
2
7.04
5
7.06
1
7.06
4
7.08
0
7.08
3
7.18
4
7.20
0
7.21
2
7.22
2
7.23
3
7.24
3
7.25
3
7.27
3
7.28
3
7.29
3
7.36
1
1.00
1.04
1.94
0.99
1.03
2.00
0.97
2.02
6.35
0.90
2.05
1.00
apr-61 PROTON CDCl3 14/11/2016
4j
-
S44
13C NMR spectrum of 4j
200 180 160 140 120 100 80 60 40 20 0 ppm
44
.08
63
.84
76
.76
77
.08
77
.39
80
.42
92
.04
10
9.3
3
11
6.7
6
11
8.6
6
12
3.2
9
12
3.8
8
12
3.9
7
12
5.3
6
12
5.6
4
12
6.8
6
12
7.4
5
12
7.8
2
12
8.0
0
12
8.2
5
12
8.9
2
12
9.3
9
13
0.2
6
13
0.3
0
13
2.6
1
13
5.5
3
14
0.3
1
14
2.7
5
15
1.8
2
17
5.4
9
4j
-
S45
1H NMR spectrum of 4k
9 8 7 6 5 4 3 2 1 0 ppm
4.94
4
5.09
2
5.12
5
5.15
4
5.18
7
5.72
4
6.26
8
6.75
3
6.77
3
6.98
7
7.00
6
7.02
7
7.04
5
7.23
8
7.24
2
7.25
8
7.27
5
7.27
8
7.30
4
7.31
5
7.32
4
7.32
9
7.34
0
7.34
5
7.37
0
7.38
5
7.40
5
7.67
3
2.00
2.08
0.99
0.98
1.03
2.05
6.47
1.00
0.97
APR-66 PROTON CDCl3 24/01/2017
4k
-
S46
13C NMR spectrum of 4k
200 180 160 140 120 100 80 60 40 20 0 ppm
44
.09
64
.58
76
.77
77
.08
77
.40
80
.47
84
.10
86
.16
92
.99
10
9.6
2
12
2.8
6
12
3.5
1
12
5.5
3
12
7.3
7
12
7.6
2
12
7.8
7
12
8.3
1
12
8.9
5
13
0.7
1
13
5.2
6
13
5.4
7
13
8.3
6
14
2.7
5
14
6.2
0
15
1.7
5
17
4.6
4
4k
-
S47
1H NMR spectrum of 4l
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.25
5
1.62
9
4.83
3
4.87
3
4.88
0
4.92
0
5.03
2
5.06
6
5.09
9
5.13
3
5.66
6
6.22
7
6.61
2
6.63
3
6.94
7
7.16
0
7.18
1
7.27
4
7.29
1
7.32
1
7.33
7
7.61
4
8.00
4
2.00
1.99
0.93
0.94
0.96
0.92
0.88
4.79
0.95
0.92
apr-99 PROTON CDCl3 18/5/2017
4l
-
S48
13C NMR spectrum of 4l
200 180 160 140 120 100 80 60 40 20 0 ppm
44
.18
64
.48
76
.77
77
.09
77
.40
80
.59
84
.25
86
.30
92
.63
11
0.7
0
12
2.2
9
12
5.9
8
12
7.2
9
12
7.7
5
12
8.0
4
12
9.0
0
12
9.0
4
12
9.1
4
13
0.6
4
13
4.8
0
13
5.4
6
13
9.0
8
14
1.2
7
14
6.4
0
15
1.7
4
17
4.2
2
4l
-
S49
1H NMR spectrum of 4m
9 8 7 6 5 4 3 2 1 0 ppm3
.08
37
4.8
73
1
4.9
03
4
4.9
51
3
4.9
81
6
6.6
13
4
6.6
32
8
6.8
00
0
6.8
18
7
6.8
37
4
6.8
99
8
6.9
18
6
6.9
34
6
6.9
43
6
6.9
62
4
7.0
68
0
7.0
90
4
7.1
26
3
7.1
45
7
7.1
61
8
7.1
79
6
7.1
95
4
7.2
13
4
7.2
87
9
7.3
06
3
7.3
25
0
7.3
89
0
7.4
08
7
7.4
26
9
7.6
92
3
2.9
4
2.0
0
0.9
7
1.0
0
3.8
9
1.0
0
3.9
4
0.9
8
0.9
9
1.9
7
0.9
7
apr-109 PROTON CDCl3 7/6/2017
4m
-
S50
13C NMR spectrum of 4m
200 180 160 140 120 100 80 60 40 20 0 ppm
26
.37
63
.06
76
.84
77
.16
77
.47
80
.45
94
.42
10
8.3
8
11
7.1
8
11
8.7
5
12
3.2
7
12
3.9
4
12
5.4
7
12
5.7
5
12
6.8
2
12
7.9
8
12
8.0
4
12
8.3
8
12
8.5
9
12
8.6
6
12
9.4
3
13
0.2
6
13
0.4
3
13
0.9
4
13
2.6
9
13
5.0
9
13
6.5
1
14
4.0
7
15
2.0
1
17
5.3
1
4m
-
S51
1H NMR spectrum of 4n
9 8 7 6 5 4 3 2 1 0 ppm
-0.000
4.555
4.594
4.847
4.881
5.013
5.053
5.087
5.088
5.293
6.452
6.658
6.677
6.909
6.920
6.926
6.930
6.943
6.947
6.968
6.987
7.000
7.012
7.015
7.031
7.033
7.050
7.052
7.131
7.133
7.138
7.151
7.155
7.170
7.191
7.196
7.207
7.213
7.227
7.233
0.9
9
1.0
0
1.9
9
0.2
8
0.9
5
0.9
9
7.9
0
3.9
6
1.0
0
1.8
9
4n
-
S52
13C NMR spectrum of 4n
200 180 160 140 120 100 80 60 40 20 0 ppm
43
.92
62
.81
76
.75
77
.07
77
.38
94
.73
10
9.7
4
11
6.8
4
12
1.7
9
12
3.7
0
12
3.7
4
12
5.6
3
12
6.0
0
12
6.5
8
12
7.1
7
12
7.4
2
12
7.8
7
12
8.7
1
12
9.3
8
12
9.4
4
13
1.0
0
13
2.7
0
13
5.0
1
13
7.3
4
13
7.5
5
14
2.9
4
14
7.8
1
15
2.6
5
17
4.5
3
4n
-
S53
1H NMR spectrum of 4o
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
2
1.2
59
4
1.7
16
5
4.8
60
9
4.8
94
4
5.0
40
3
5.0
74
1
6.3
82
9
6.8
10
5
6.8
30
0
6.9
07
5
6.9
28
1
6.9
42
9
6.9
62
7
6.9
82
1
7.0
01
1
7.0
08
5
7.0
28
0
7.0
35
9
7.0
57
8
7.2
31
1
7.2
35
5
7.2
48
9
7.2
53
8
7.2
61
9
7.2
82
6
7.3
85
7
7.4
04
7
8.0
29
1
8.0
50
9
1.2
0
1.1
5
1.0
3
1.0
8
5.1
8
3.0
2
1.2
3
2.2
8
1.0
0
apr-176 PROTON CDCl3 2/11/2017
4o
-
S54
13C NMR spectrum of 4o
200 180 160 140 120 100 80 60 40 20 0 ppm
62
.85
76
.74
77
.06
77
.38
81
.77
94
.81
11
0.7
4
11
6.8
5
12
1.8
4
12
3.8
0
12
3.8
9
12
5.9
4
12
6.0
0
12
6.5
2
12
7.8
6
12
9.1
4
12
9.4
7
13
1.1
0
13
2.2
3
13
7.3
7
13
8.1
1
14
0.8
8
14
7.7
8
15
2.6
1
17
6.6
1
4o
-
S55
1H NMR spectrum of 4p
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
002
1.65
87
4.41
42
4.45
36
4.88
10
4.91
16
4.91
87
4.94
92
5.14
52
5.18
45
5.26
35
6.51
52
6.53
49
6.54
78
6.56
84
6.81
68
6.83
37
6.84
89
6.86
78
6.96
16
6.97
99
6.99
80
7.07
07
7.09
28
7.11
27
7.16
65
7.18
33
7.20
18
7.21
37
7.23
20
7.23
51
7.33
02
7.34
83
7.36
70
7.43
50
7.45
38
0.97
2.00
1.02
3.02
2.92
1.98
2.07
3.21
1.06
3.00
2.09
0.93
apr-182 PROTON CDCl3 29/11/2017
4p
-
S56
13C NMR spectrum of 4p
200 180 160 140 120 100 80 60 40 20 0 ppm
43
.78
62
.86
76
.80
77
.12
77
.44
80
.82
94
.60
95
.16
10
9.5
5
11
6.9
6
11
8.6
8
13
0.5
6
13
2.5
8
13
5.0
1
13
5.3
5
13
5.9
2
13
7.7
8
14
3.0
3
15
1.8
4
17
5.2
4
4p
-
S57
1H NMR spectrum of 4q
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.65
9
3.79
6
4.90
6
4.94
5
5.00
9
5.04
8
5.24
7
5.28
5
5.29
4
5.63
6
5.67
4
6.35
1
6.51
1
6.52
9
6.54
4
6.54
9
6.58
3
6.58
9
6.60
4
6.61
0
6.78
5
6.80
5
6.87
0
6.88
8
6.90
6
6.92
2
6.93
7
6.94
0
7.12
3
7.14
2
7.16
1
7.18
2
7.20
8
7.22
4
7.22
8
7.28
2
3.00
0.80
0.91
0.98
0.95
0.81
2.99
0.91
1.93
9.08
apr-190 b PROTON CDCl3 20/12/2017
4q
-
S58
13C NMR spectrum of 4q
200 180 160 140 120 100 80 60 40 20 0 ppm
44
.28
55
.45
65
.39
76
.76
77
.08
77
.40
81
.50
92
.72
10
2.2
0
10
8.4
7
10
9.5
9
11
9.6
7
11
9.8
2
12
3.4
7
12
5.3
7
12
6.1
9
12
6.6
5
12
7.7
5
12
7.8
3
12
8.4
3
12
8.8
5
12
9.0
3
13
0.5
8
13
5.6
5
13
8.6
3
14
1.5
0
14
3.0
0
14
3.4
6
15
1.1
3
15
3.9
7
16
0.3
6
17
4.8
8
4q
-
S59
1H NMR spectrum of 5
11 10 9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.6
65
5.0
49
7.0
73
7.0
92
7.1
11
7.1
64
7.1
85
7.2
63
7.3
60
7.5
58
7.5
62
7.5
80
7.5
97
7.6
01
7.8
59
7.8
63
7.8
78
7.8
82
10
.51
8
2.0
0
0.9
5
0.9
5
1.8
9
0.9
6
0.9
0
0.9
1
5
-
S60
13C NMR spectrum of 5
200 180 160 140 120 100 80 60 40 20 0 ppm
57
.25
76
.75
77
.06
77
.38
85
.03
87
.41
11
3.3
9
12
1.6
9
12
2.4
3
12
5.5
9
12
8.6
5
13
1.7
4
13
5.7
7
15
9.9
8
18
9.6
5
5
-
S61
1H NMR spectrum of 6
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
1.60
5
3.09
1
4.78
6
4.80
6
4.81
9
4.83
8
4.93
9
4.96
3
4.97
1
4.99
7
5.29
8
6.30
7
6.57
1
6.62
5
6.71
6
6.73
7
6.75
8
6.84
7
6.85
5
6.86
6
6.87
5
6.88
3
6.90
2
6.91
3
6.93
1
6.94
1
6.95
1
6.95
9
6.97
1
6.98
9
7.19
7
7.21
6
7.23
6
7.27
5
7.29
5
3.00
0.95
0.97
0.89
1.80
1.02
2.00
1.81
3.38
APR161 PROTON CDCl3 9/10/2017
6
-
S62
13C NMR spectrum of 6
200 180 160 140 120 100 80 60 40 20 0 ppm
26
.47
63
.15
76
.73
77
.05
77
.37
81
.22
94
.33
10
8.6
7
11
6.6
8
12
1.5
0
12
3.4
6
12
5.5
5
12
6.3
6
12
6.4
8
12
6.5
6
12
8.1
6
12
8.3
4
12
9.1
8
13
0.7
3
13
1.0
9
13
3.5
1
13
5.5
3
14
3.9
5
15
2.6
8
17
4.7
6
6
-
S63
1H NMR spectrum of 7
9 8 7 6 5 4 3 2 1 0 ppm
2.52
0
3.47
5
3.74
9
4.67
3
4.67
8
4.69
8
4.70
3
4.73
7
5.04
5
5.08
5
6.67
0
6.68
9
6.90
6
7.00
4
7.02
4
7.04
1
7.05
0
7.06
9
7.18
0
7.19
9
7.21
1
7.21
9
7.22
8
7.24
6
7.27
0
7.29
0
7.31
1
7.33
7
7.34
6
7.36
4
7.39
7
7.41
5
1.00
3.05
3.40
2.92
1.06
1.06
0.88
3.36
8.41
1.12
apr-328 PROTON CDCl3 23/08/2018
7
-
S64
13C NMR spectrum of 7
200 180 160 140 120 100 80 60 40 20 0 ppm
44
.11
52
.40
52
.70
56
.11
76
.02
76
.79
77
.11
77
.43
78
.35
83
.73
89
.48
10
9.5
9
11
2.1
1
12
1.8
2
12
3.2
3
12
5.3
0
12
6.1
7
12
7.2
7
12
7.4
1
12
7.6
9
12
8.2
4
12
8.8
0
13
0.1
4
13
0.8
5
13
1.7
8
13
5.4
9
14
3.7
9
14
7.3
3
15
5.0
7
16
0.9
9
16
3.0
9
17
3.8
1
apr-328 C13CPD CDCl3 23/08/2018
7
-
S65
1H NMR spectrum of 8
9 8 7 6 5 4 3 2 1 0 ppm
-0.0
00
2
1.5
73
1
2.5
40
5
2.5
46
3
2.5
52
0
3.8
61
6
3.8
82
3
4.4
25
3
4.4
45
6
4.4
65
8
4.8
33
8
4.8
39
6
4.8
66
9
4.9
59
1
4.9
98
3
6.5
31
3
6.5
51
1
6.7
69
0
6.7
88
6
6.9
87
8
7.0
06
5
7.0
25
2
7.0
41
7
7.0
64
9
7.0
86
1
7.0
98
9
7.1
17
1
7.2
35
4
7.2
57
1
7.2
68
8
7.2
88
0
7.3
02
9
7.3
28
9
7.3
37
2
7.3
74
1
7.3
93
6
7.4
07
0
7.4
11
3
1.0
0
0.9
6
1.0
1
3.0
7
1.1
0
0.9
5
0.9
9
5.1
1
11
.01
1.2
0
apr-289 PROTON CDCl3 7/8/2018
8
-
S66
13C NMR spectrum of 8
200 180 160 140 120 100 80 60 40 20 0 ppm
43
.81
49
.45
52
.04
56
.43
75
.69
78
.70
83
.89
10
9.7
8
11
1.5
8
12
1.3
3
12
3.0
8
12
3.4
3
12
5.1
1
12
5.5
0
12
6.1
4
12
6.6
5
12
7.3
1
12
7.9
1
12
8.6
2
12
8.9
9
12
9.1
6
13
1.0
1
13
1.6
1
13
5.0
9
14
3.4
3
15
4.8
5
17
2.9
1
17
3.1
0
17
5.7
5
8
-
S67
1H NMR spectrum of 9
9 8 7 6 5 4 3 2 1 0 ppm
1.31
43
1.33
23
1.35
02
1.65
99
2.56
10
2.56
65
2.57
23
3.60
07
3.70
74
3.72
55
3.74
33
3.76
09
3.77
88
3.80
78
3.84
31
3.86
11
3.87
91
3.89
67
3.91
45
3.93
23
4.70
86
4.71
44
4.74
82
4.75
39
4.77
89
4.78
46
4.81
84
4.82
42
6.88
22
6.90
24
6.90
80
7.06
73
7.08
87
7.10
84
7.12
72
7.30
34
7.36
59
7.38
60
7.40
01
7.40
49
7.43
30
7.45
13
7.58
21
7.58
49
3.00
0.85
2.90
0.96
2.99
1.07
2.04
1.95
3.05
3.09
1.02
apr-288 PROTON CDCl3 4/1/2019
9
-
S68
13C NMR spectrum of 9
200 180 160 140 120 100 80 60 40 20 0 ppm
12
.32
34
.92
52
.28
52
.60
56
.11
75
.93
78
.36
83
.70
89
.54
10
8.5
5
11
2.1
2
12
1.7
9
12
2.9
2
12
5.4
3
12
6.3
3
12
7.4
7
12
8.2
4
13
0.0
5
13
0.8
4
13
2.1
1
14
3.7
4
14
6.7
6
15
5.0
9
16
0.9
4
16
3.0
7
17
3.1
9
9
-
S69
Solid-state arrangements of compound 4i
A unit cell contains two asymmetric units of 4i. The solid-state arrangements of compound 4i
divulged a number of close intermolecular links between the molecules, which are associated via
intermolecular five C-H---O hydrogen bonding interactions that are described as given below:
For C(14)–H(14)---O(4): H(14)---O(4) = 2.480 Å and < C(14)–H(14)---O(4) = 134.75o
For C(20)-H(20)---O(3): H(42)---O(3) = 2.360 Å and < C(20)-H(20)---O(3) = 162.77o
For C(28)-H(28)---O(6): H(28)---O(6) = 2.689 Å and < C(28)-H(28)---O(6) = 147.28 o
For C(38)-H(38)---O(1): H(38)---O(1) = 2.569 Å and < C(38)-H(38)---O(1) = 133.23o
For C(42)-H(42)---O(6): H(42)---O(6) = 2.448 Å and < C(42)-H(42)---O(6) = 168.65o
The three C–H···π interactions that are described as given below:
1. C(35)-H(35B)---Cg(1); H(35B)---Cg(1) = 2.586 Å and
-
S70
Figure 3. A partial packing view of 4i showing hydrogen bondings
Figure 4. The molecular arrangement of compound 4i viewed through b-axis.
-
S71
Figure 5. Energy minimization based on MM2 calculations for 3a and 4a
==============