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Supporting Information

for

‘‘On water’’ cascade synthesis of benzopyranopyrazoles and their macrocycles

Sengodagounder Muthusamy* and Chinnakuzhanthai Gangadurai

School of Chemistry, Bharathidasan University, Tiruchirappalli - 620024, India

*Corresponding author Tel.: +91-431-2407053; fax: +91-431-2407045

E-mail: [email protected]

1. Experimental Section S02

2. General procedure for the synthesis propynyloxy benzaldehydes 3a-l S02-S05

3. General procedure for the synthesis of benzopyranopyrazoles (BPP) 5a-l and

pyrazole incorporated macrocycles 12a-c S05-S13

4. Selected 1H, 13C, DEPT-135 NMR and HRMS spectra for

compounds 5a-l, 6a,b, 8b and 12b,c S13-S63

5. Solid-state arrangement of compound 6b S63-S67

6. Solid-state arrangement of compound 8b S68-S70

S1

mailto:[email protected]

Experimental Section

All reactions were carried out in well-cleaned glass wares. Analytical thin-layer

chromatography (TLC) was performed on Merck 60 F254 silica gel plates and the

components of mixtures were made visual by observation under iodine or UV light, or by

sulfuric acid charring. Column chromatography was performed on Merck silica gel (100–200

mesh). Melting points were obtained and are uncorrected. FT-IR spectra were recorded using

a Bruker Alpha-T spectrophotometer using the ATR technique. 1H and 13C NMR spectra (400

MHz and 100 MHz, respectively) were obtained using a Bruker Avance 400 spectrometer

and are referenced to TMS. Multiplicities are indicated as singlet (s), doublet (d), triplet (t),

quartet (q), multiplet (m), or variants thereof. Coupling constants (J) are reported in hertz

(Hz). Carbon types were determined from DEPT 13C NMR experiments. High-resolution

mass spectra were determined on Thermo Fisher EXACTIVE PLUS EMR spectrometers

using the ESI technique.

General experimental procedure for the synthesis of 2-[(prop-2-ynyl)oxy]benzaldehydes 3a-l

Salicylaldehyde was dissolved in DMF (5 mL, distilled from CaH2). Propargyl bromide and

potassium carbonate were added at 0 °C, and the reaction mixture was stirred at room

temperature for prescribed time indicated. After completion of the reaction (monitored by

TLC), water (10 mL) was added and extracted with ethyl acetate (3x15 mL). The combined

organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under

reduced pressure. Subsequent column chromatography using silica gel with ethyl

acetate−hexanes yielded the corresponding 2-(prop-2-ynyloxy)benzaldehydes in good yield.

2-[(Prop-2-yn-1-yl)oxy]benzaldehyde (3a). According to the general procedure, the

appropriate salicylaldehyde (200 mg, 1.67 mmol), propargyl bromide (215 mg, 1.8 mmol)

and potassium carbonate (272 mg, 1.9 mmol) were reacted for 10 h.

Subsequent workup and column chromatography purification furnished 256

mg of the title compound as a white solid in 97% yield; mp 87-89 oC; IR

(ATR): νmax 3267, 2973, 2872, 1680, 1596, 1481, 1454, 1286, 1218, 1193,

1104, 1007, 925 cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.47 (s, 1H, CHO), 7.83 (d, J = 7.2 Hz,

1H, ArH), 7.57-7.53 (m, 1H, ArH), 7.12-7.05 (m, 2H, ArH), 4.81 (d, J = 2.0 Hz, 2H, OCH2),

2.60 (s, 1H, CH); 13C NMR (CDCl3, 100 MHz) δ 189.4 (C=O), 159.8 (quat-C), 135.7 (CH),

128.5 (CH), 125.5 (quat-C), 121.7 (CH), 113.3 (CH), 77.7 (quat-C), 76.6 (CH), 56.4 (CH2).

S2

3a

3-Methoxy-2-[(prop-2-yn-1-yl)oxy]benzaldehyde (3b). According to the general procedure,

the apt salicylaldehyde (200 mg, 1.31 mmol), propargyl bromide (172 mg,

1.44 mmol) and potassium carbonate (218 mg, 1.57 mmol) were reacted for

10 h. Subsequent workup and column chromatography provided 239 mg of

the title compound as a white solid in 95% yield; mp 71-73 oC; IR (ATR):

νmax 3283, 2944, 2875, 2758, 1686, 1585, 1585, 1476, 1392, 1251, 1199,

1067, 982 cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.50 (s, 1H, CHO), 7.43 (t, J = 2.4 Hz, 1H,

ArH), 7.15 (d, J = 3.2 Hz, 2H, ArH), 4.87 (s, 2H, OCH2), 3.89 (s, 3H, OCH3), 2.51 (t, J = 2.4

Hz, 1H, =CH); 13C NMR (CDCl3, 100 MHz) δ 190.5 (CHO), 152.8 (quat-C), 149.5 (quat-C),

131.1 (quat-C), 124.9 (CH), 118.8 (CH), 117.8 (CH), 78.3 (CH), 76.9 (quat-C), 60.8 (CH2),

56.0 (CH3).

5-Methoxy-2-[(prop-2-yn-1-yl)oxy]benzaldehyde (3c). According to the general procedure,


1.44 mmol) and potassium carbonate (218 mg, 1.57 mmol) were reacted

for 10 h. Subsequent workup and column chromatography afforded 204 mg

of the title compound as a white solid in 81% yield; mp 69-71 oC; IR

(ATR): νmax 3280, 2948, 2874, 1684, 1585, 1469, 1253, 1192, 1068, 984, 914, 780 cm-1; 1H

NMR (CDCl3, 400 MHz) δ 10.43 (s, 1H, CHO), 7.38 (t, J = 3.2 Hz, 1H, ArH), 7.11 (d, J =

3.2 Hz, 2H, ArH), 4.82 (d, J = 2.0 Hz, 2H, OCH2), 3.84 (s, 3H, OCH3), 2.46 (t, J = 2.0 Hz

1H, =CH); 13C NMR (CDCl3, 100 MHz) δ 189.1 (CHO), 151.4 (quat-C), 148.1 (quat-C),

129.7 (quat-C), 123.5 (CH), 117.4 (CH), 116.4 (CH), 76.9 (quat-C), 75.5 (CH), 59.4 (CH2),

54.6 (CH3).

5-Nitro-2-[(prop-2-yn-1-yl)oxy]benzaldehyde (3d). According to the general procedure, the

apt salicylaldehyde (200 mg, 1.19 mmol), propargyl bromide (156 mg, 1.31

mmol) and potassium carbonate (200 mg, 1.43 mmol) were reacted for 12 h.

Subsequent workup and column chromatography gave 217 mg of the title

compound as a white solid in 88% yield; mp 79-81 oC; IR (ATR): νmax 3384,

3249, 3074, 2928, 2890, 2839, 1670, 1600, 1443, 1301, 1264, 1204, 1106,

1011, 823 cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.43 (s, 1H, CHO), 8.70-8.65 (m, 1H, ArH),

8.46-8.41 (m, 1H, ArH), 7.30 (d, J = 9.2 Hz, 1H, ArH), 5.00 (s, 2H, OCH2), 2.70 (t, J = 2.4


142.1 (quat-C), 130.3 (CH), 125.2 (quat-C), 124.5 (CH), 113.8 (CH), 76.3 (CH), 57.2 (CH2).

S3

3b

3c

3d

4-Methoxy-2-[(prop-2-yn-1-yl)oxy]benzaldehyde (3e). According to the general procedure,



11 h. Subsequent workup and column chromatography gave 228 mg of the

title compound as a white solid in 91% yield; mp 63-65 oC; IR (ATR): νmax

3291, 3074, 3002, 2874, 1672, 1596, 1482, 1450, 1292, 1219, 1014, 928 cm-1; 1H NMR

(CDCl3, 400 MHz) δ 10.30 (s, 1H, CHO), 7.82 (d, J = 9.2 Hz, 1H, ArH), 6.59 (q, J = 3.6 Hz,

2H, ArH), 4.80 (d, J = 2.0 Hz, 2H, OCH2), 3.87 (d, J = 1.2 Hz, 3H, OCH3), 2.60 (t, J = 2.0


130.6 (CH), 119.5 (quat-C), 106.9 (CH), 99.4 (CH), 77.6 (CH), 76.6 (CH), 56.4 (CH2), 55.7

(CH3).

5-Chloro-2-[(prop-2-yn-1-yl)oxy]benzaldehyde (3f). According to the general procedure,

the appropriate salicylaldehyde (250 mg, 1.59 mmol), propargyl bromide (208 mg, 1.75

mmol) and potassium carbonate (264 mg, 1.91 mmol) were reacted for 10 h. Subsequent

workup and column chromatography furnished 268 mg of the title compound as a white solid

in 86% yield; mp 81-83 oC; IR (ATR): νmax 3232, 3070, 2981, 2880, 2769, 1674, 1587, 1473,

1398, 1269, 1217, 1183, 1125, 1003, 885 cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.39 (s, 1H,

CHO), 7.77 (s, 1H, CH), 7.51-7.48 (m,1H, ArH), 7.08 (d, J = 8.8 Hz, 1H,

ArH), 4.83 (d, J = 1.6 Hz, 2H, OCH2), 2.62 (s, 1H, CH); 13C NMR (CDCl3,

100 MHz) δ 188.1 (CHO), 158.2 (quat-C), 135.2 (CH), 128.0 (CH), 127.4

(quat-C), 126.4 (quat-C), 115.1 (CH), 77.3 (CH), 77.0 (quat-C), 56.8 (CH2).

5-Bromo-2-[(prop-2-yn-1-yl)oxy]benzaldehyde (3g). According to the general procedure,



10 h. Subsequent workup and column chromatography afforded 258 mg of

the title compound as a white solid in 86% yield; mp 93-95 oC; IR (ATR):

νmax 3296, 1685, 1590, 1474, 1393, 1264, 1218, 1181, 1123, 1018, 929, 895

cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.37 (s, 1H, CHO), 7.91 (d, J = 2.8 Hz, 1H, CH,), 7.63

(dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H, ArH), 7.03 (d, J = 9.2 Hz, 1H, ArH), 4.83 (s, 2H, OCH2),

2.63 (t, J = 2.4 Hz, 1H, CH); 13C NMR (CDCl3, 100 MHz) δ 188.0 (C=O), 158.6 (quat-C),

138.1 (CH), 131.1 (CH), 126.8 (quat-C), 115.4 (CH), 114.5 (quat-C), 77.5 (quat-C), 76.8

(CH), 56.7 (CH2).

S4

3e

3g

3f

3j

2-[(Prop-2-yn-1-yl)oxy]-1-naphthaldehyde (3h). According to the general procedure, the

appropriate salicylaldehyde (200 mg, 1.16 mmol), propargyl bromide (151 mg,

1.27 mmol) and potassium carbonate (192 mg, 1.39 mmol) were reacted for 10

h. Subsequent workup and column chromatography using silica gel provided

207 mg of the title compound as a white solid in 84% yield; mp 84-86 oC; IR

(ATR): νmax 3298, 3054, 2883, 1673, 1619, 1510, 1460, 1370, 1341, 1265,

1214, 1179, 1056, 1024, 947, 915 cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.89 (s, 1H, CHO),

9.26 (d, J = 8.4 Hz, 1H, ArH), 8.04 (d, J = 9.2 Hz, 1H, ArH), 7.77 (d, J = 7.6 Hz, 1H, ArH),

7.62 (t, J = 7.6 Hz, 1H, ArH), 7.43 (t, J = 6.0 Hz, 1H, ArH), 7.36 (d, J = 9.2 Hz, 1H, ArH),

4.92 (d, J = 1.6 Hz, 2H, OCH2), 2.60 (s, 1H, CH); 13C NMR (CDCl3, 100 MHz) δ 191.8

(CHO), 161.9 (quat-C), 137.2 (CH), 131.4 (quat-C), 129.8 (CH), 129.2 (CH), 128.3 (CH),

125.2 (CH), 125.1 (CH), 118.1 (quat-C), 114.1 (CH), 77.7 (quat-C), 76.8 (CH), 57.5 (CH2).

3,5-Di-tert-butyl-2-[(prop-2-yn-1-yl)oxy]benzaldehyde (3i). According to the general

procedure, the appropriate salicylaldehyde (150 mg, 0.64 mmol), propargyl

bromide (83 mg, 0.70 mmol) and potassium carbonate (106 mg, 0.76 mmol)

were reacted for 10 h. Subsequent workup and column chromatography using

silica gel yielded 151 mg of the title compound as a white solid in 86% yield;

mp 96-98 oC; IR (ATR): νmax 3201, 3079, 2900, 1656, 1490, 1451, 1435,


1H, ArH), 7.64 (d, J = 2.8 Hz 1H, ArH), 4.64 (d, J = 2.4 Hz, 2H, OCH2), 2.62 (t, J = 2.4 Hz,

1H, CH), 1.46 (s, 9H, (CH3)3), 1.33 (s, 9H, (CH3)3); 13C NMR (CDCl3, 100 MHz) δ 190.7

(CHO), 158.4 (quat-C), 147.1 (quat-C), 143.3 (quat-C), 131.0 (quat-C), 129.5 (CH), 124.6

(CH), 78.2 (CH), 76.7 (CH), 65.0 (CH2), 35.4 (quat-C), 34.7 (quat-C), 31.3 (CH3), 31.0

(CH3).

3-Ethoxy-2-[(prop-2-yn-1-yl)oxy]benzaldehyde (3j). According to the general procedure,

the apt salicylaldehyde (150 mg, 0.90 mmol), propargyl bromide (118 mg, 0.99

mmol) and potassium carbonate (149 mg, 1.0 mmol) were reacted for 10 h.

Subsequent workup and column chromatography using silica gel gave 168 mg

of the title compound as a white solid in 91% yield; mp 112-114 oC; IR (ATR):

νmax 3243, 2813, 2358, 1669, 1653, 1637, 1558, 1541, 1522, 1457, 1120, 1082,

936, 700 cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.50 (s, 1H, CHO), 7.43 (t, J = 5.2 Hz, 1H,

ArH), 7.14 (d, J = 4.0 Hz, 2H, ArH), 4.91 (d, J = 2.4 Hz, 2H, OCH2), 4.10 (q, J = 6.8 Hz, 2H,

OCH2), 2.50 (t, J = 2.4 Hz, 1H, CH), 1.48 (t, J = 6.8 Hz, 3H, CH3); 13C NMR (CDCl3, 100

S5

3h

3i

MHz) δ 190.6 (CHO), 152.1 (quat-C), 149.6 (quat-C), 131.1 (quat-C), 124.8 (CH), 118.8

(CH), 118.7 (CH), 78.4 (CH), 64.6 (CH2), 60.7 (CH2), 14.8 (CH3).

3,5-Diiodo-2-[(prop-2-yn-1-yl)oxy]benzaldehyde (3k). According to the general procedure,

the appropriate salicylaldehyde (150 mg, 0.40 mmol), propargyl bromide (52

mg, 0.44 mmol) and potassium carbonate (66 mg, 0.48 mmol) were reacted for

10 h. Subsequent workup and column chromatography provided 154 mg of the

title compound as a white solid in 93% yield; mp 137-139 oC; IR (ATR): νmax

3301, 2959, 2871, 1685, 1595, 1469, 1395, 1363, 1234, 1202, 1163, 1115, 995,

955, 907, 818, 730, 676 cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.32 (s, 1H, CHO), 8.36 (d, J =

2.0 Hz, 1H, ArH), 8.16 (d, J = 2.0 Hz, 1H, ArH), 4.85 (d, J = 2.4 Hz, 2H, OCH2), 2.59 (t, J =

2.4 Hz, 1H, CH); 13C NMR (CDCl3, 100 MHz) δ 188.3 (CHO), 159.4 (quat-C), 152.6 (CH),

137.4 (CH), 132.9 (quat-C), 94.1 (quat-C), 90.3 (quat-C), 78.9 (CH), 76.9 (quat-C), 62.6

(CH2).

5-Bromo-3-methoxy-2-[(prop-2-yn-1-yl)oxy]benzaldehyde (3l). According to the general

procedure, the apt salicylaldehyde (150 mg, 0.40 mmol), propargyl bromide

(52 mg, 0.44 mmol) and potassium carbonate (66 mg, 0.48 mmol) were

reacted for 10 h. Subsequent workup and column chromatography gave 154

mg of the title compound as a white solid in 93% yield; mp 153-154 oC; IR

(ATR): νmax 3178, 3081, 2924, 2855, 1740, 1547, 1466, 1446, 1420, 1350,


1H, ArH), 7.17 (d, J = 2.4 Hz, 1H, ArH), 4.80 (d, J = 2.4 Hz, 2H, OCH2), 3.84 (s, 3H, OCH3),

2.42 (t, J = 2.4 Hz, 1H, CH); 13C NMR (CDCl3, 100 MHz) δ 189.1 (CHO), 153.7 (quat-C),

148.5 (quat-C), 132.0 (quat-C), 121.6 (CH), 120.7 (CH), 117.9 (quat-C), 77.8 (CH), 77.4

(quat-C), 60.9 (CH2), 56.4 (CH3).

General procedure for the synthesis of benzopyranopyrazoles (BPP) 5. The appropriate

aldehyde was transferred to a round bottom flask in double distilled water (2 mL). To this, p-

toluene sulfonylhydrazide and potassium carbonate were added, and the mixture was stirred

for 12 h at 70 °C until complete transformation to the desired pyrazole. After cooling down to

room temperature, additional 3 mL of water was added, and extracted with ethyl acetate. The

combined organic layers were washed with brine, dried over Na2SO4, and concentrated under

reduced pressure. The residue was recrystallized from diethyl ether to afford the

corresponding benzopyranopyrazoles (BPP).

S6

3k

3l

2,4-Dihydro[1]benzopyrano[4,3-c]pyrazole (5a). According to the general procedure, the

appropriate aldehyde (100 mg, 0.62 mmol), p-toluene sulfonylhydrazide (127 mg, 0.68

mmol) and potassium carbonate (129 mg, 0.93 mmol) were reacted at 70 °C for 10 h.

Subsequent workup and recrystallization from diethyl ether furnished the title compound as a

white solid (95 mg) in 89% yield; mp 129-131 oC; IR (ATR): νmax 3291, 2924, 1602, 1489,

1457, 1353, 1224, 1168, 1089, 1023, 904, 756 cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.65 (dd,

J1 = 7.6 Hz, J2 = 1.2 Hz, 1H, ArH), 7.34 (s, 1H, CH), 7.21-7.17 (m, 1H, ArH), 6.98-6.93 (m,

2H, ArH), 5.29 (s, 2H, OCH2); 13C NMR (CDCl3, 100 MHz) δ 154.1 (quat-C),

141.9 (quat-C), 129.5 (CH), 125.7 (CH), 122.2 (CH), 121.8 (CH), 117.7 (quat-

C), 117.3 (CH), 111.6 (quat-C), 63.8 (CH2); HRMS (ESI) Calcd. for C10H8N2O

[M+H]+ 173.0715; found 173.0711.

6-Methoxy-2,4-dihydro[1]benzopyrano[4,3-c]pyrazole (5b). According to the general

procedure, the apt aldehyde (100 mg, 0.52 mmol), p-toluene sulfonylhydrazide

(107 mg, 0.57 mmol) and potassium carbonate (109 mg, 0.78 mmol) were

reacted at 70 °C for 11 h. Subsequent workup and recrystallization from diethyl

ether afforded the title compound as a white solid (102 mg) in 96% yield; mp

159-161 oC; IR (ATR): νmax 3318, 3161, 2928, 1566, 1469, 1444, 1341, 1261,

1203, 1171, 1104, 1030, 987, 864 cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.36 (s, 1H, ArH),

7.30 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H, ArH), 6.91 (t, J = 8.0 Hz, 1H, ArH), 6.84 (dd, J1 = 8.0

Hz, J2 = 0.8 Hz, 1H, ArH), 5.38 (s, 2H, OCH2), 3.90 (s, 3H, OCH3); 13C NMR (CDCl3, 100

MHz) δ 148.9 (quat-C), 143.1 (quat-C), 142.0 (quat-C), 125.5 (CH), 121.6 (CH), 118.5

(quat-C), 114.4 (CH), 112.0 (CH), 111.5 (quat-C), 64.3 (CH2), 56.1 (CH3); HRMS (ESI)

Calcd. for C11H10N2O2 [M+H]+ 203.0821; found 203.0819.

8-Methoxy-2,4-dihydro[1]benzopyrano[4,3-c]pyrazole (5c). According to the general

procedure, the appropriate aldehyde (100 mg, 0.52 mmol), p-toluene

sulfonylhydrazide (107 mg, 0.57 mmol) and potassium carbonate (109

mg, 0.78 mmol) were reacted at 70 °C for 10 h. Subsequent workup and

recrystallization from diethyl ether yielded the title compound as a white

solid (101 mg) in 95% yield; mp 151-153 oC; IR (ATR): νmax 3320, 3161,

2930, 1598, 1470, 1443, 1262, 1203, 1172, 1105, 1031, 864 cm-1; 1H NMR (CDCl3, 400

MHz) δ 7.30 (s, 1H, ArH), 7.25 (dd, J1 = 7.6 Hz, J2 = 0.8 Hz, 1H, CH), 6.86 (t, J = 8.0 Hz,

1H, ArH), 6.78 (dd, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H, ArH), 5.32 (s, 2H, CH2), 3.84 (s, 3H,

OCH3); 13C NMR (CDCl3, 100 MHz) δ 147.9 (quat-C), 142.1 (quat-C), 141.0 (quat-C), 124.5

S7

5b

5c

5a

(CH), 120.6 (CH), 117.5 (CH), 113.4 (CH), 111.0 (CH), 110.5 (CH), 63.3 (CH2), 55.1 (CH3);

HRMS (ESI) Calcd. for C11H10N2O2 [M+H]+ 203.0820; found 203.0813.

7-Methoxy-2,4-dihydro[1]benzopyrano[4,3-c]pyrazole (5d). According

to the general procedure, the appropriate aldehyde (100 mg, 0.52 mmol),

p-toluene sulfonylhydrazide (107 mg, 0.57 mmol), and potassium

carbonate (109 mg, 0.78 mmol) were reacted at 70 °C for 10 h. Subsequent

workup and recrystallisation from diethyl ether provided the title

compound as a white solid (96 mg) in 90% yield; mp 169-171 oC; IR

(ATR): νmax 3148, 2933, 1624, 1465, 1307, 1279, 1252, 1194, 1155, 1113, 1016, 958, 842 cm-

1; 1H NMR (DMSO-d6, 400 MHz) δ 12.8 (br, 1H, NH), 7.52 (d, J = 8.0 Hz, 2H, ArH), 6.58

(dd, J1 = 8.4 Hz, J2 = 3.2 Hz, 1H, ArH), 6.51 (d, J = 2.0 Hz, 1H, ArH), 5.24 (s, 2H, OCH2),

3.73 (s, 3H, OCH3); 13C NMR (DMSO-d6, 100 MHz) δ 160.0 (quat-C), 154.6 (quat-C), 122.6

(CH), 109.4 (quat-C), 107.7 (CH), 102.4 (CH), 63.8 (CH2), 55.1 (CH3); HRMS (ESI) Calcd.

for C11H10N2O2 [M+H]+ 203.0820; found 203.0816.

8-Nitro-2,4-dihydro[1]benzopyrano[4,3-c]pyrazole (5e). According to the general


sulfonylhydrazide (99 mg, 0.53 mmol), and potassium carbonate (101 mg,

0.73 mmol) were reacted at 70 °C for 12 h. Subsequent workup and

recrystallization from diethyl ether gave the title compound as a pale

yellow solid (93 mg) in 88% yield; mp 157-159 oC; IR (ATR): νmax 3057, 1597, 1264, 1157,

1091, 1012, 894, 805, 728 cm-1; 1H NMR (DMSO-d6, 400 MHz) δ 13.26 (br, 1H, NH), 8.45

(s, 1H, CH), 8.11 (d, J = 7.6 Hz, 1H, ArH), 7.73 (d, J = 7.2 Hz, 1H, ArH), 7.16 (d, J = 8.8

Hz, 1H, ArH), 5.55 (s, 2H, CH2); 13C NMR (DMSO-d6, 100 MHz) δ 158.7 (quat-C), 142.9

(quat-C), 141.4 (quat-C), 135.1 (quat-C), 129.5 (CH), 127.6 (CH), 124.6 (CH), 117.7 (CH),

116.8 (quat-C), 65.1 (CH2); HRMS (ESI) Calcd. for C10H7N3O3 [M+Na]+ 240.0385; found

240.0385

8-Chloro-2,4-dihydro[1]benzopyrano[4,3-c]pyrazole (5f). According to the general

procedure, the appropriate aldehyde (100 mg, 0.51 mmol), p-toluene sulfonylhydrazide (105

mg, 0.56 mmol) and potassium carbonate (106 mg, 0.77 mmol) were reacted at 70 °C for 12

h. Subsequent workup and recrystallization from diethyl ether yielded the title compound as a


1263, 1216, 991, 729 cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.67 (s, 1H, ArH), 7.40 (s, 1H,

S8

5d

5e

5f

CH), 7.14 (dd, J1 = 8.8 Hz, J2 = 2.0 Hz, 1H, ArH), 6.90 (d, J = 8.8 Hz, 1H, ArH), 5.31 (s, 2H,

CH2); 13C NMR (CDCl3, 100 MHz) δ 152.6 (quat-C), 141.9 (quat-C), 129.2 (CH), 126.8

(quat-C), 124.7 (CH), 122.0 (CH), 119.2 (quat-C), 118.6 (CH), 111.8 (quat-C), 63.8 (CH2);

HRMS (ESI) Calcd. for C10H7ClN2O [M+H]+ 207.0325; found 207.0324

8-Bromo-2,4-dihydro[1]benzopyrano[4,3-c]pyrazole (5g). According to the general

procedure, the apt aldehyde (100 mg, 0.41 mmol), p-toluene

sulfonylhydrazide (85 mg, 0.46 mmol) and potassium carbonate (86 mg,


recrystallization from diethyl ether furnished the title compound as a white

solid (98 mg) in 93% yield; mp 144-146 oC; IR (ATR): νmax 3147, 2915,

2679, 1469, 1458, 1353, 1219, 992, 1050, 794 cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.84 (d, J

= 2.4 Hz, 1H, ArH), 7.36 (s, 1H, CH), 7.25 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H, ArH), 6.82 (dd,

J1 = 8.4 Hz, J2 = 2.4 Hz, 1H, ArH), 5.31 (s, 2H, CH2); 13C NMR (CDCl3, 100 MHz) δ 152.9

(quat-C), 131.7 (CH), 125.3 (CH), 124.9 (CH), 120.0 (quat-C), 118.9 (CH), 113.9 (quat-C),

111.3 (quat-C), 64.0 (CH2); HRMS (ESI) Calcd. for C10H7BrN2O [M+H]+ 250.9820; found

250.9822.

2,4-Dihydronaphtho[1’,2’:5,6]pyrano[4,3-c]pyrazole (5h). According to the general


sulfonylhydrazide (97 mg, 0.52 mmol) and potassium carbonate (98 mg, 0.71

mmol) were reacted at 70 °C for 12 h. Subsequent workup and

recrystallisation from diethyl ether afforded the title compound as a white

solid (96 mg) in 91% yield; mp 181-183 oC; IR (ATR): νmax 3175, 3055, 2926, 2854, 1622,

1596, 1585, 1522, 1455, 1432, 1378, 1218, 1018, 1003, 985, 815 cm-1; 1H NMR (CDCl3, 400

MHz) δ 9.23 (d, J = 8.4 Hz, 1H, ArH), 7.80 (d, J = 8.0 Hz, 1H, ArH), 7.73 (d, J = 8.8 Hz, 1H,

ArH), 7.56 (t, J = 8.0, 1H, ArH), 7.40 (t, J = 8.0 Hz, 1H, ArH), 7.26 (s, 1H, ArH), 7.22 (d, J =

5.2 Hz, 1H, CH), 5.32 (s, 2H, OCH2); 13C NMR (CDCl3, 100 MHz) δ 153.2 (quat-C), 144.2

(quat-C), 129.9 (quat-C), 129.81 (quat-C), 129.77 (CH), 128.3 (CH), 127.3 (CH), 125.8

(CH), 124.1 (CH), 123.3 (CH), 118.7 (CH), 112.4 (quat-C), 111.8 (quat-C), 63.4 (OCH2);

HRMS (ESI) Calcd. for C14H10N2O [M+Na]+ 245.0691; found 245.0690.

6,8-Di-tert-butyl-2,4-dihydro[1]benzopyrano[4,3-c]pyrazole (5i). According to the general

procedure, the appropriate aldehyde (100 mg, 0.36mmol), p-toluene

sulfonylhydrazide (75 mg, 0.40mmol) and potassium carbonate (75 mg,

S9

5g

5h

5i

0.55 mmol) were reacted at 70 °C for 12 h. Subsequent workup and recrystallisation from

diethyl ether gave the title compound as a white solid (93 mg) in 89% yield; mp 187-189 oC;

IR (ATR): νmax 3316, 3177, 2935, 1566, 1470, 1444, 1261, 1203, 1167, 1104, 863, 787, 729

cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.59 (d, J = 2.0 Hz, 1H, ArH), 7.37 (s, 1H, ArH), 7.26 (d,

J = 4.8 Hz, 1H, ArH), 5.21 (s, 2H, OCH2), 1.41 (s, 9 H, (CH3)3), 1.26 (s, 9H, (CH3)3); 13C

NMR (CDCl3, 100 MHz) δ 150.2 (quat-C), 143.8 (quat-C), 138.2 (quat-C), 125.6 (CH),

124.1 (CH), 117.9 (CH), 117.1 (quat-C), 111.9 (quat-C), 62.7 (CH2), 35.0 (quat-C), 34.5

(quat-C), 31.5 (CH3), 29.9 (CH3); HRMS (ESI) Calcd. for C18H24N2O[M+H]+ 285.1966;

found 285.1962.

6-Ethoxy-2,4-dihydro[1]benzopyrano[4,3-c]pyrazole (5j). According to the general

procedure, the apt aldehyde (100 mg, 0.48 mmol), p-toluene sulfonylhydrazide (100 mg, 0.53

mmol), and potassium carbonate (101 mg, 0.73 mmol) were reacted at 70 °C for 12 h.

Subsequent workup and recrystallization from diethyl ether provided the title compound as a


1566, 1466, 1261, 1195, 1109, 1040, 992, 732 cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.71 (s,

1H, NH), 7.40 (s, 1H, CH), 7.31 (t, J = 7.6 Hz, 1H, ArH), 6.94-6.86 (m, 2H, ArH), 5.40 (s,

2H, OCH2), 4.15 (q, J = 7.2 Hz, 2H, OCH2), 1.49 (t, J = 6.8 Hz, 3H, CH3); 13C NMR (CDCl3,

100 MHz) δ 148.2 (quat-C), 143.5 (quat-C), 121.6 (CH), 118.5 (quat-C), 114.5 (CH), 113.6

(CH), 64.6 (CH2), 64.2 (CH2), 60.5 (quat-C), 21.1 (CH), 14.9 (CH3); HRMS (ESI) Calcd. for

C12H12N2O2[M+H]+ 217.0977; found 217.0976.

6,8-Diiodo-2,4-dihydro[1]benzopyrano[4,3-c]pyrazole (5k). According to

the general procedure, the apt aldehyde (100 mg, 0.24 mmol), p-toluene

sulfonylhydrazide (49 mg, 0.26 mmol), and potassium carbonate (50 mg,


recrystallisation from diethyl ether yielded the title compound as a white

solid (96 mg) in 94% yield; mp 187-189 oC; IR (ATR): νmax 3168, 2938, 2857, 1624, 1589,

1526, 1429, 1380, 1221, 1173, 1090, 1021, 993 cm-1; 1H NMR (CDCl3, 400 MHz) δ 13.13 (s,

1H, NH), 7.8 (d, J = 2.0 Hz, 1H, ArH), 7.86 (s, 1H, ArH), 7.63 (s, 1H, CH), 5.37 (s, 2H,

OCH2); 13C NMR (CDCl3, 100 MHz) δ 152.6 (quat-C), 144.4 (CH), 140.3 (quat-C), 129.7

(CH), 124.2 (CH), 121.3 (quat-C), 110.1 (quat-C), 87.6 (quat-C), 85.4 (quat-C), 64.8 (CH2);

HRMS (ESI) Calcd. for C10H6I2N2O[M+H]+ 424.8647; found 424.8649.

S10

5j5k

8-Bromo-6-methoxy-2,4-dihydro[1]benzopyrano[4,3-c] pyrazole (5l). According to the

general procedure, the corresponding aldehyde (100 mg, 0.37 mmol), p-toluene

sulfonylhydrazide (76 mg, 0.41 mmol), and potassium carbonate (77 mg, 0.56 mmol) were

reacted at 70 °C for 15 h. Subsequent workup and recrystallisation from diethyl ether

furnished the title compound as a white solid (81 mg) in 77% yield; Mp 161-163 oC; IR

(ATR): νmax 3156, 2926, 1466, 1255, 1219, 1036, 993, 807, 771 cm-1; 1H NMR (CDCl3, 400

MHz) δ 7.48 (s, 1H, ArH), 7.39 (d, J = 2.0 Hz, 1H, ArH), 6.98 (d, J = 2.0 Hz, 1H, ArH), 5.29

(s, 2H, OCH2), 3.82 (s, 3H, OCH3); 13C NMR (CDCl3, 100 MHz) δ 149.4 (quat-C), 141.5

(quat-C), 125.4 (quat-C), 120.2 (quat-C), 116.2 (CH), 114.4 (CH), 112.7

(quat-C), 110.6 (quat-C), 63.8 (CH2), 55.9 (CH3); HRMS (ESI) Calcd.

for C11H9BrN2O2 [M+H]+ 280.9925; found 280.9918.

tert-Butyl 6-methoxy[1]benzopyrano[4,3-c]pyrazole-2(4H)-

carboxylate (6a). The selected chromenopyrazole compound 6b (30 mg,

0.14 mmol) was dissolved in dichloromethane (2 mL), to this, Boc-

anhydride (35 mg, 0.16 mmol), triethylamine (16 mg, 0.16 mmol) and a catalytic amount of

DMAP were added sequentially at 0 oC under nitrogen atmosphere. The reaction was brought

up to room temperature and stirred for additional 6 h. After complete consumption of starting

material monitored by TLC, ice-cold water (3 mL) was added and the organic layer was

separated and dried over Na2SO4 and the solvent was evaporated under reduced pressure.

Purification of the crude product by column chromatography using silica gel afforded the

desired product 6a as a pale brown solid (34 mg) in 78% yield; mp 163-164 oC; IR (ATR):

νmax 2980, 2934, 1746, 1573, 1477, 1441, 1352, 1250, 1149, 953, 1341, 1287, 1250, 1219,

1148, 1086, 1046, 991, 958, 886, 864, 732 cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.87 (s, 1H,

ArH), 7.57 (d, J = 7.6 Hz, 1H, ArH), 7.00 (t, J = 8.0 Hz, 1H, ArH), 6.91 (d, J = 8.0 Hz, 1H,

ArH), 5.33 (s, 2H, OCH2), 3.90 (s, 3H, OCH3), 1.66 (s, 9H, (CH3)3); 13C

NMR (CDCl3, 100 MHz) δ 148.8 (CO), 147.7 (quat-C), 144.3 (CH), 125.0

(CH), 121.8 (CH), 117.6 (quat-C), 115.8 (CH), 115.3 (quat-C), 113.0 (CH),

85.6 (quat-C), 63.2 (CH2), 56.0 (OCH3), 27.9 ((CH3)3); HRMS (ESI) Calcd.

for C16H18N2O4[M+Na]+ 325.1164; found 325.1146.

tert-Butyl 8-chloro[1]benzopyrano[4,3-c]pyrazole-2(4H)-carboxylate (6b). The selected

chromenopyrazole compound 5f (50 mg, 0.24 mmol) was dissolved in dichloromethane (3

mL). To this, Boc-anhydride (58 mg, 0.26 mmol), triethyl amine (26 mg, 0.26 mmol) and

catalytic amount of DMAP were added sequentially at 0 oC under nitrogen atmosphere. The

S11

5l

6a

6b

reaction was brought up to room temperature and stirred for additional 6 h. After complete

consumption of starting material monitored by TLC, ice-cold water (3 mL) was added and

the organic layer was separated and dried over Na2SO4 and the solvent was evaporated under

reduced pressure. Purification of the crude product by column chromatography using silica

gel yielded the desired product 6b as a fluffy white solid (71 mg) in 95% yield; mp 141-143 oC; IR (ATR): νmax 2968, 2868, 1623, 1598, 1511, 1471, 1404, 1353, 1229, 1103, 1088 cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.92 (t, J = 2.4 Hz, 1H, ArH), 7.87 (s, 1H, ArH), 7.20 (q, J =

6.4 Hz, 1H, ArH), 6.90 (d, J = 8.4 Hz, 1H, ArH), 5.25 (s, 2H, CH2), 1.67 (s, 9H, (CH3)3); 13C

NMR (CDCl3, 100 MHz) δ 153.5 (CO), 146.7 (quat-C), 130.6 (CH), 127.1 (quat-C), 125.1

(CH), 123.4 (CH), 118.8 (CH), 118.1 (quat-C), 115.1 (quat-C), 85.8 (quat-C), 63.0 (CH2),

28.0 ((CH3)3); HRMS (ESI) Calcd. for C15H15ClN2O3 [M+Na]+ 329.0668; found 329.0670.

Crystal Data for Compound 6b

The product was recrystallized using EtOAc and hexanes. C15H15ClN2O3, M = 306.74, crystal

size 0.30 × 0.19 × 0.12 mm, monoclinic, space group P21/n, with a = 7.033(10) Å, b =

16.00(2) Å, c = 13.681(18) Å, a = 90°, b = 100°, g = 90°, V = 1516.9(4) Å3, T = 296 K, R1=

0.0389, wR2 = 0.1138 on observed data, Z = 4, Dcalcd = 1.343 g cm–3, F(000) = 640, absorption

coefficient = 0.263 mm–1, l = 0.71073 Å, 3835 reflections were collected on a Smart Apex

CCD single crystal diffractometer, 3323 observed reflections [I > 2σ(I)]. The largest

difference peak and hole are 0.30 and –0.29 eÅ–3 respectively. The structure was solved by

direct methods and refined by full-matrix least squares on F2 using SHELXL-97 software

(CCDC 1511317).

3,3a,4,11c-Tetrahydronaphtho[1’,2’:5,6]pyrano[4,3-c] pyrazole (8b). According to the

general procedure, appropriate aldehyde (200 mg, 0.5 mmol), tosylhydrazide (96 mg, 0.5

mmol), and potassium carbonate (97 mg, 0.7 mmol) were reacted for 10 h at

70 °C. Subsequent workup and recrystallisation from diethyl ether provided

the title compound as a brown needles (92 mg) in 87% yield; mp 178-180 oC;

IR (ATR): νmax 2968, 2868, 1623, 1598, 1545, 1229, 1088, 1031, 814, 749 cm-

1; 1H NMR (CDCl3, 400 MHz) δ 8.68 (d, J = 8.4 Hz, 1H, ArH), 7.87 (d, J = 8.4 Hz, 1H, ArH),

7.79 (d, J = 9.2 Hz, 1H, ArH), 7.68 (td, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H, ArH), 7.52-7.80 (m, 1H,

ArH), 7.14 (d, J = 8.8 Hz, 1H, ArH), 5.50 (d, J = 6.8 Hz, 1H, CH), 4.73 (dt, J1 = 17.4 Hz, J2 =

1.72 Hz, 1H, CH2), 4.53 (ddd, J1 = 17.3 Hz, J2 = 7.2 Hz, J3 = 3.0 Hz, 1H, CH2), 4.16 (dd, J1 =

11.0 Hz, J2 = 5.4 Hz, 1H, CH2), 3.21 (t, J1 = 11.6 Hz, 1H, CH2), 2.74-2.66 (m, 1H, CH); 13C

S12

8b

NMR (CDCl3, 100 MHz) δ 153.5 (quat-C), 133.5 (quat-C), 130.0 (CH), 129.6 (quat-C),

128.5 (CH), 127.2 (CH), 124.2 (CH), 123.9 (CH), 118.6 (CH), 110.4 (quat-C), 82.5 (CH),

78.4 (CH), 65.0 (CH2), 29.0 (CH2); HRMS (ESI) Calcd. for C14H12N2O [M+H]+ 225.1027

found 225.1024.

Crystal Data for Compound 8b

The product was recrystallized using EtOAc and hexanes. C14H12N2O, M = 224.26, crystal

size 0.29 × 0.23 × 0.17 mm, orthorhombic, space group P212121, with a = 5.1418(3) Å, b =

8.3699(4) Å, c = 25.9032(14) Å, a = 90°, b = 90°, g = 90°, V = 1114.78(10) Å3, T = 293 K,

R1= 0.0524, wR2 = 0.1443 on observed data, Z = 4, Dcalcd = 1.336 g cm–3, F(000) = 472,

absorption coefficient = 0.086 mm–1, l = 0.71073 Å, 3623 reflections were collected on a

Bruker Smart Apex II single crystal diffractometer, 2180 observed reflections [I > 2\s(I)].

The largest difference peak and hole are 0.134 and –0.133 eÅ–3, respectively. The structure

was solved by direct methods and refined by full-matrix least squares on F2 using SHELXL-

97 software (CCDC 1580213).

Prop-2-yn-1-yl 2-[3-(2-formylphenoxy)propoxy]benzoate (11a). According to the general

procedure, alkylbromo tethered aldehyde 7a (200 mg, 0.82 mmol), alkynylhydroxy

compound 8 (159 mg, 0.90 mmol), K2CO3 (134 mg, 0.98 mmol) were reacted for 12 h.

Subsequent workup and column chromatography purification using silica gel gave 220 mg of

the title compound as a colourless solid in 79% yield; mp 107-109 oC; IR (ATR): νmax 2945,

2823, 1730, 1689, 1587, 1483, 1450, 1296, 1236, 1159, 1031 cm-1; 1H NMR (CDCl3, 400

MHz) δ 10.50 (s, 1H, CHO), 7.83 (ddd, J1 = 16.4 Hz, J2 = 8.0 Hz, J3 = 1.6 Hz, 2H, ArH,),

7.55-7.46 (m, 2H, ArH), 7.09-6.98 (m, 4H, ArH), 4.86 (d, J = 7.6 Hz, 2H, OCH2), 4.40 (t, J =

6.0 Hz, 2H, OCH2), 4.26 (t, J = 5.6 Hz, 2H, OCH2), 2.47 (s, 1H, CH2), 1.81 (m, 2H, CH); 13C

NMR (CDCl3, 100 MHz) δ 189.6 (CHO), 165.2 (CO), 161.2 (quat-C), 158.6 (quat-C), 136.0

(CH), 134.1 (CH), 132.1 (CH), 128.4 (CH), 124.9 (quat-C), 120.7

(CH), 120.5 (CH), 119.2 (quat-C), 113.1 (CH), 112.7 (CH), 77.9

(CH), 74.9 (CH), 65.0 (CH2), 64.9 (CH2), 52.2 (CH2), 29.1 (CH2) ;

Anal. Calcd. for C20H18O5: C, 70.99; H, 4.56. Found: C, 71.26; H,

4.29.

S13

11a

Prop-2-yn-1-yl 2-{[9-(2-formylphenoxy)nonyl]oxy}benzoate (11b). According to the

general procedure, the alkylbromo tethered aldehyde 7b (200 mg, 0.61 mmol),

alkynylhydroxy compound 8 (118 mg, 0.67 mmol), potassium carbonate (99 mg, 0.73 mmol)

were reacted for 12 h. Subsequent workup and column chromatography purification using

silica gel furnished 217 mg of the title compound as a colourless solid in 84% yield; mp 121-

123 oC; IR (ATR): νmax 2929, 2855, 1732, 1686, 1598, 1488, 1455, 1298, 1240, 1168, 1040

cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.52 (s, 1H, CHO), 7.82 (d, J = 7.2 Hz, 2H, ArH), 7.54-

7.43 (m, 2H, ArH), 7.02-6.94 (m, 4H, ArH), 4.89 (s, 2H, OCH2), 4.09-4.02 (m, 4H, OCH2),

2.48 (s, 1H, CH), 1.84-1.49 (m, 14H, CH2); 13C NMR (CDCl3, 100 MHz) δ 192.1 (CHO),

163.7 (CO), 161. 3 (quat-C), 159.0 (quat-C), 157.9 (quat-C), 137.5 (CH), 131.6 (CH), 129.8

(CH), 128.4 (CH), 125.7 (quat-C), 124.7 (CH), 116.6 (CH), 113.6 (CH), 78.7 (quat-C), 76.4

(CH), 69.5 (CH2), 34.1 (CH2), 32.8 (CH2), 29.4 (CH2), 29.3 (CH2), 29.2 (CH2), 28.7 (CH2),

28.6 (CH2), 28.1 (CH2), 28.12 (CH2); Anal. Calcd.

for C26H30O5: C, 73.91; H, 7.16. Found: C, 74.18; H,

7.02.

Prop-2-yn-1-yl 2-{[10-(2-

formylphenoxy)decyl]oxy}benzoate (11c).

According to the general procedure, the alkylbromo tethered aldehyde 7c (100 mg, 0.58

mmol), alkynylhydroxy compound 8 (113 mg, 0.64 mmol), potassium carbonate (95 mg, 0.70

mmol) were reacted for 12 h. Subsequent workup and column chromatography purification

using silica gel afforded 207 mg of the title compound as a colourless solid in 81% yield; mp

134-136 oC; IR (ATR): νmax 2943, 2912, 1736, 1660, 1587, 1464, 1451, 1278, 1253, 1169,

1043 cm-1; 1H NMR (CDCl3, 400 MHz) δ 10.90 (s, 1H, CHO), 8.01 (d, J = 7.4 Hz, 2H, ArH),

7.74-7.62(m, 2H, ArH), 7.53-7.33 (m, 4H, ArH), 4.93 (s, 2H, OCH2), 4.11-4.06 (m, 4H,

OCH2), 2.51 (s, 1H, CH), 1.86-1.51 (m, 16H, CH2); 13C NMR (CDCl3, 100 MHz) δ 192.1

(CHO), 163.7 (CO), 161. 3 (quat-C), 159.0 (quat-C), 157.9 (quat-C), 137.5 (CH), 131.6

(CH), 129.8 (CH), 128.4 (CH), 125.7 (quat-C),

124.7 (CH), 116.6 (CH), 113.6 (CH), 78.7

(quat-C), 76.4 (CH), 69.5 (CH2), 34.1 (CH2),

32.8 (CH2), 29.4 (CH2), 29.3 (CH2), 29.2 (CH2),

28.7 (CH2), 28.6 (CH2), 28.1 (CH2), 28.12

(CH2), 26.0 (CH2); Anal. Calcd. for C27H32O5: C, 74.29; H, 7.39. Found: C, 74.52; H, 7.54.

S14

11b

11c

2,10,11,19-Tetrahydro-9H,17H-dibenzo[13,14:6,7][1,5,9] trioxacyclotetradecino[12,11-

c]pyrazol-17-one (12a). According to the general procedure, appropriate aldehyde (100 mg,

0.29 mmol), p-toluene sulfonylhydrazide (60 mg, 0.32 mmol), and potassium carbonate (61

mg, 0.44 mmol) were reacted at 70 °C for 12 h. Subsequent workup and recrystallization

from diethyl ether afforded the title compound as a colorless thick oil (64 mg) in 62% yield;

IR (ATR): νmax 2929, 1736, 1684, 1450, 1411, 1264, 1197, 1148, 1028, 760 cm-1; 1H NMR

(CDCl3, 400 MHz) δ 7.90 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H, ArH,), 7.84 (dd, J1 =7.8 Hz, J2 =

1.9 Hz, 1H, ArH), 7.71-7.69 (m, 2H, ArH), 7.18 (d, J = 8.0 Hz, 1H, ArH), 7.04 (q, J = 6.8

Hz, 3H, ArH), 6.51 (s, 1H, ArH), 4.90 (d, J = 2.4 Hz, 2H, OCH2), 4.41 (t, J = 6.2 Hz, 2H,

OCH2), 4.28 (t, J = 5.8 Hz, 2H, OCH2), 3.94 (s, 2H, OCH2); 13C NMR (CDCl3, 100 MHz) δ

166.5 (CO), 161.3 (quat-C), 159.1 (quat-C), 144.3 (quat-C), 146.6 (quat-C), 135.7 (CH),

134.0 (CH), 132.2 (CH), 128.8 (CH), 124.8 (quat-C), 120.7 (CH), 120.5 (CH), 120.4 (CH),

119.2 (quat-C), 113.1 (CH), 112.7 (CH), 65.4(CH2), 64.1 (CH2), 52.2 (CH2), 29.6 (CH2);

Anal. Calcd. for C20H18N2O4: C, 68.56; H, 5.18; N, 8.00. Found: C, 68.88; H, 5.41; N, 8.24.

7,8,9,10,11,12,13,14,22,25-decahydro-6H,20H-dibenzo[2,3:9,10]

[1,5,11]trioxacycloeicosino[8,7-c]pyrazol-20-one (12b).

According to the general procedure, the apt aldehyde (100 mg, 0.23

mmol), p-toluene sulfonylhydrazide (48 mg, 0.26 mmol), and

potassium carbonate (49 mg, 0.35 mmol) were reacted at 70 °C for 10 h. Subsequent workup

and recrystallisation from diethyl ether gave the title compound as a white solid (84 mg) in

82% yield; mp 177-179 oC; IR (ATR): νmax 2981, 2930, 1736, 1684, 1265, 1197, 1029, 761,

721 cm-1; 1H NMR (CDCl3, 400 MHz) δ 11.11 (s, 1H, NH), 7.78 (d, J = 6.8 Hz, 1H, ArH),

7.67 (d, J = 7.2 Hz, 1H, ArH), 7.33 (t, J = 6.8 Hz 1H, ArH), 7.20 (t, J = 8.0 Hz, 1H, ArH),

6.97-6.83 (m, 3H, ArH), 6.66 (s, 1H, ArH), 5.35 (s, 2H, OCH2), 4.15 (s, 2H, OCH2), 3.86 (t, J

= 6.4 Hz, 2H, OCH2), 1.80-1.70 (m, 8H, CH2), 1.25-1.18 (m, 6H, CH2); 13C NMR (CDCl3,

100 MHz) δ 189.8 (CO), 165.5 (quat-C), 161.6 (quat-C), 159.0 (quat-

C), 135.8 (CH), 133.8 (CH), 131.9 (CH), 129.5 (CH), 125.1 (quat-C),

128.3 (CH), 120.5 (CH), 120.0 (CH), 113.3 (CH), 112.6 (CH), 78.0

(quat-C), 74.6 (quat-C), 69.0 (CH2), 68.6 (CH2), 52.1 (CH2), 45.9

(CH2), 29.4 (CH2), 29.2 (CH2), 29.2 (CH2), 29.1 (CH2), 26.0 (CH2),

25.9 (CH2); HRMS (ESI) Calcd. for C26H30N2O4 [M+Na]+ 457.2103;

found 457.2105.

S15

12a

12b

6,7,8,9,10,11,12,13,14,15,23,26-dodecahydro-21H-dibenzo [2,3:9,10]

[1,5,11]trioxacycloheneicosino[8,7-c]pyrazol-21-one (12c). According to the general

procedure, the apt aldehyde (100 mg, 0.22 mmol), p-toluene sulfonylhydrazide (46 mg, 0.25

mmol), and potassium carbonate (46 mg, 0.33 mmol) were reacted at 70 °C for 10 h.

Subsequent workup and recrystallisation from diethyl ether provided the title compound as a

white solid (82 mg) in 80% yield; mp 183-185oC; IR (ATR): νmax 3175, 2926, 2854, 1621,

1596, 1522, 1432, 1377, 1218, 1017, 815 cm-1; 1H NMR (CDCl3, 400 MHz) δ 11.50 (s, 1H,

NH), 7.83 (d, J = 6.4 Hz, 1H, ArH), 7.65 (d, J = 7.2 Hz, 1H, ArH), 7.39 (t, J = 7.2 Hz, 1H,

ArH), 7.27-7.24 (m, 2H, ArH), 7.02-6.89 (m, 3H, ArH), 6.71 (s, 1H, ArH), 5.40 (s, 2H,

OCH2), 4.20 (s, 2H, OCH2), 3.92 (t, J = 6.4 Hz, 2H, OCH2), 1.85 (s,

2H, CH2), 1.67 (d, J = 6.0 Hz, 2H, CH2), 1.53 (t, J = 6.0 Hz, 4H,

CH2), 1.30-1.23 (m, 8H, CH2); 13C NMR (CDCl3, 100 MHz) δ 191.0

(CO), 166.7 (quat-C), 162.8 (quat-C), 160.2 (quat-C), 137.0 (CH),

135.0 (CH), 133.1 (CH), 130.1 (CH), 129.5 (quat-C), 126.3 (CH),

123.2 (CH), 121.7 (CH), 114.5 (CH), 113.8 (CH), 79.2 (quat-C),

75.9 (quat-C), 70.2 (CH2), 69.8 (CH2), 53.3 (CH2), 47.1 (CH2), 30.6

(CH2), 30.4 (CH2), 30.43 (CH2), 30.30 (CH2), 27.4 (CH2), 27.1 (CH2); Anal. Calcd. for

C27H32N2O4: C, 72.30; H, 7.19; N, 6.25. Found: C, 72.49; H, 7.21; N, 6.31.

S16

12c

(1) Selected NMR and HRMS spectra for benzopyranopyrazoles 5a-l, 6a,b, 8b & 12b,c

10 9 8 7 6 5 4 3 2 1 0 ppm

5.293

6.929

6.932

6.951

6.953

6.969

6.975

7.172

7.175

7.192

7.193

7.196

7.210

7.214

7.341

7.641

7.644

7.660

7.663

2.01

1.96

1.00

0.95

1.00

NAME Jun24-2016-SMCGDEXPNO 2PROCNO 1Date_ 20160624Time 10.16INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT CDCl3NS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 203DW 60.800 usecDE 6.50 usecTE 296.3 KD1 1.00000000 secTD0 1

======== CHANNEL f1 ========NUC1 1HP1 14.10 usecPL1 -1.00 dBPL1W 12.39612865 WSFO1 400.1324710 MHzSI 32768SF 400.1300164 MHzWDW EMSSB 0LB 0.30 HzGB 0PC 1.00

CGD-425PROTON CDCl3 24/06/16

200 180 160 140 120 100 80 60 40 20 0 ppm

63.80

76.73

77.05

77.37

111.57

117.29

117.71

121.83

122.17

125.67

129.54

141.92

154.05

NAME Jun24-2016-SMCGDEXPNO 4PROCNO 1Date_ 20160624Time 11.31INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT CDCl3NS 1024DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 297.3 KD1 2.00000000 secD11 0.03000000 secTD0 1

======== CHANNEL f1 ========NUC1 13CP1 10.50 usecPL1 -2.00 dBPL1W 55.73500443 WSFO1 100.6228298 MHz

======== CHANNEL f2 ========CPDPRG2 waltz16NUC2 1HPCPD2 80.00 usecPL2 -1.00 dBPL12 14.14 dBPL13 15.00 dBPL2W 12.39612865 WPL12W 0.37956488 WPL13W 0.31137666 WSFO2 400.1316005 MHzSI 32768SF 100.6127690 MHzWDW EMSSB 0LB 1.00 HzGB 0PC 1.40

CG-425C13CPD CDCl3 24/06/16

S17

13C NMR spectrum of compound 5a

1H NMR spectrum of compound 5a

200 180 160 140 120 100 80 60 40 20 0 ppm

63.80

117.29

121.83

122.17

125.69

129.54

NAME Jun24-2016-SMCGDEXPNO 5PROCNO 1Date_ 20160624Time 11.47INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT CDCl3NS 256DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 296.7 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1

======== CHANNEL f1 ========NUC1 13CP1 10.50 usecP2 21.00 usecPL1 -2.00 dBPL1W 55.73500443 WSFO1 100.6228298 MHz

======== CHANNEL f2 ========CPDPRG2 waltz16NUC2 1HP3 14.00 usecP4 28.00 usecPCPD2 80.00 usecPL2 -1.00 dBPL12 14.14 dBPL2W 12.39612865 WPL12W 0.37956488 WSFO2 400.1316005 MHzSI 32768SF 100.6127690 MHzWDW EMSSB 0LB 1.00 HzGB 0PC 1.40

CGD-425C13DEPT135 CDCl3 24/06/16

S18

DEPT-135 NMR spectrum of compound 5a

S19

HRMS spectrum of compound 5a

10 9 8 7 6 5 4 3 2 1 0 ppm

3.898

5.377

6.832

6.834

6.852

6.854

6.897

6.917

6.937

7.264

7.299

7.301

7.317

7.320

7.359

3.00

1.96

2.00

2.03

NAME May03-2016-SMCGDEXPNO 12PROCNO 1Date_ 20160503Time 11.22INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT CDCl3NS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 181DW 60.800 usecDE 6.50 usecTE 298.6 KD1 1.00000000 secTD0 1



200 180 160 140 120 100 80 60 40 20 0 ppm

56.06

64.25

76.75

77.07

77.38

111.46

111.99

114.44

118.50

121.59

125.48

141.95

143.10

148.92

NAME May03-2016-SMCGDEXPNO 13PROCNO 1Date_ 20160503Time 11.42INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT CDCl3NS 250DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 299.7 KD1 2.00000000 secD11 0.03000000 secTD0 1



CGD-458C13CPD CDCl3

S20

1H NMR spectrum of compound 5b

13C NMR spectrum of compound 5b

200 180 160 140 120 100 80 60 40 20 0 ppm

56.06

64.25

111.98

114.43

121.60

125.51

NAME May03-2016-SMCGDEXPNO 14PROCNO 1Date_ 20160503Time 11.58INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT CDCl3NS 256DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 299.3 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1



CGD-458C13DEPT135 CDCl3

S21

DEPT-135 NMR spectrum of compound 5b

HRMS spectrum of compound 5b

13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm

3.84

1

5.32

06.77

56.77

86.79

56.79

86.84

16.86

06.88

07.24

27.24

47.26

17.26

37.30

2

3.18

2.04

1.04

1.04

1.00

1.00




200 180 160 140 120 100 80 60 40 20 0 ppm

55.07

63.26

75.76

76.08

76.40

110.48

111.00

113.45

117.52

120.61

124.49

140.96

142.11

147.93

NAME Jun18-2016-SMCGDEXPNO 11PROCNO 1Date_ 20160618Time 12.52.INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT CDCl3NS 250DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 299.7 KD1 2.00000000 secD11 0.03000000 secTD0 1



CGD-464C13CPD CDCl3 18/06/16

S22

13C NMR spectrum of compound 5c


200 180 160 140 120 100 80 60 40 20 0 ppm

54.90

63.10

110.82

113.28

120.44

124.36

CGD-464C13DEPT135 CDCl3

S23

DEPT-135 spectrum of compound 5c

S24

HRMS spectrum of compound 5c

14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm

3.462

3.725

5.238

6.513

6.518

6.569

6.575

6.590

6.596

7.507

7.527

12.772

3.22

2.00

0.95

1.00

1.93

0.54

NAME Sep26-2016-SMCGDEXPNO 5PROCNO 1Date_ 20160926Time 10.19INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT DMSONS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 64DW 60.800 usecDE 6.50 usecTE 293.8 KD1 1.00000000 secTD0 1


CGD-478PROTON DMSO 26/09/16

200 180 160 140 120 100 80 60 40 20 0 ppm

38.72

38.92

39.13

39.34

39.55

39.76

39.97

55.14

63.82

102.42

107.69

109.42

122.62

154.64

160.02

NAME Sep26-2016-SMCGDEXPNO 6PROCNO 1Date_ 20160926Time 10.55INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT DMSONS 512DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 295.6 KD1 2.00000000 secD11 0.03000000 secTD0 1



CGD-478C13CPD DMSO 26/09/16

S25

1HNMR spectrum of compound 5e

13C NMR spectrum of compound 5e

200 180 160 140 120 100 80 60 40 20 0 ppm

55.14

63.82

102.41

107.69

122.62

NAME Sep26-2016-SMCGDEXPNO 7PROCNO 1Date_ 20160926Time 11.11INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT DMSONS 256DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 294.9 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1



CGD-478C13DEPT135 DMSO 26/09/16

S26

DEPT-135 NMR spectrum of compound 5e

S27

HRMS spectrum of compound 5e

14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm

5.547

7.149

7.171

7.435

7.453

7.728

7.746

8.103

8.122

8.318

8.449

13.262

2.00

1.02

0.67

1.39

1.12

0.95

0.79

NAME Jul01-2016-SMCGDEXPNO 2PROCNO 1Date_ 20160701Time 10.16INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT DMSONS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 90.5DW 60.800 usecDE 6.50 usecTE 300.7 KD1 1.00000000 secTD0 1



200 180 160 140 120 100 80 60 40 20 0 ppm

20.9

138.7

838.9

939.1

939.4

039.6

139.8

240.0

3

65.1

2

110.

25116.

76117.

66124.

55127.

58129.

40135.

09141.

39142.

88

158.

72

NAME Jul01-2016-SMCGDEXPNO 3PROCNO 1Date_ 20160701Time 11.20INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT DMSONS 1024DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 300.7 KD1 2.00000000 secD11 0.03000000 secTD0 1




S28

13C NMR spectrum of compound 5d

1H NMR spectrum of compound 5d

200 180 160 140 120 100 80 60 40 20 0 ppm

20.92

65.09

116.75

117.66

124.55

127.59

129.41

NAME Jul01-2016-SMCGDEXPNO 4PROCNO 1Date_ 20160701Time 11.36INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT DMSONS 256DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 300.1 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1



CGD-460C13DEPT135 DMSO

S29

HRMS spectrum of compound 5d

DEPT-135 NMR spectrum of compound 5d

10 9 8 7 6 5 4 3 2 1 0 ppm

5.311

6.890

6.912

7.135

7.140

7.157

7.162

7.401

7.665

2.00

0.91

0.91

0.94

0.91



CGD-462PROTON CDCl317/06/16

200 180 160 140 120 100 80 60 40 20 0 ppm

63.83

76.71

77.03

77.34

111.77

118.65

119.24

122.00

124.73

126.82

129.17

141.94

152.57




CGD-462C13CPD CDCl3 17/06/16

S30

13C NMR spectrum of compound 5f

1H NMR spectrum of compound 5f

200 180 160 140 120 100 80 60 40 20 0 ppm

63.83

118.65

122.00

124.74

129.17




CGD-462C13DEPT135 CDCl3 17/06/16

S31

DEPT-135 NMR spectrum of compound 5f

S32

HRMS spectrum of compound 5f

10 9 8 7 6 5 4 3 2 1 0 ppm

5.305

6.815

6.822

6.837

6.843

7.244

7.250

7.266

7.272

7.362

7.837

7.843

2.00

1.01

1.06

1.11

1.02

NAME Jul05-2016-smcgdEXPNO 9PROCNO 1Date_ 20160705Time 10.48INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT CDCl3NS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 228DW 60.800 usecDE 6.50 usecTE 299.1 KD1 1.00000000 secTD0 1


cgd-462PROTON CDCl3 05/07/16

200 180 160 140 120 100 80 60 40 20 0 ppm

60.39

64.03

111.34

113.94

118.88

119.95

124.93

125.33

131.69

152.91

NAME Jul05-2016-smcgdEXPNO 11PROCNO 1Date_ 20160705Time 12.04INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT CDCl3NS 1024DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 300.0 KD1 2.00000000 secD11 0.03000000 secTD0 1



cgd-462C13CPD CDCl3 05/07/16

S33

13C NMR spectrum of compound 5g

1H NMR spectrum of compound 5g

200 180 160 140 120 100 80 60 40 20 0 ppm

64.03

118.89

124.93

125.33

128.11

131.70

NAME Jul05-2016-smcgdEXPNO 10PROCNO 1Date_ 20160705Time 11.05INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT CDCl3NS 256DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 299.4 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1



cgd-462C13DEPT135 CDCl3 05/07/16

S34

DEPT-135 NMR spectrum of compound 5g

S35

HRMS spectrum of compound 5g

10 9 8 7 6 5 4 3 2 1 0 ppm

5.298

7.178

7.200

7.268

7.359

7.377

7.397

7.516

7.535

7.554

7.696

7.718

7.764

7.785

9.186

9.207

2.00

0.94

0.94

1.02

0.99

0.97

1.00

0.97




200 180 160 140 120 100 80 60 40 20 0 ppm

63.44

76.74

77.05

77.26

77.37

111.83

112.47

118.71

123.22

124.14

125.85

127.31

128.30

129.85

129.97

144.26

153.26




CGD-434C13CPD CDCl3 27/06/16

S36

13C NMR spectrum of compound 5h

1H NMR spectrum of compound 5h

200 180 160 140 120 100 80 60 40 20 0 ppm

63.44

118.71

123.21

124.12

124.14

125.84

127.31

128.28

128.31

129.93

129.97




CGD-434C13DEPT135 CDCl3 27/06/16

S37

DEPT-135 NMR spectrum of compound 5h

S38

HRMS spectrum of compound 5h

13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm

1.257

1.411

5.212

7.252

7.264

7.270

7.377

7.583

7.588

9.48

9.28

2.00

1.35

1.16

1.14

NAME Oct25-2016-smcgdEXPNO 2PROCNO 1Date_ 20161025Time 11.55INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT CDCl3NS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 80.6DW 60.800 usecDE 6.50 usecTE 292.2 KD1 1.00000000 secTD0 1



200 180 160 140 120 100 80 60 40 20 0 ppm

14.15

26.93

29.90

31.46

31.61

34.47

35.04

62.71

76.73

77.05

77.36

111.92

117.06

117.94

124.13

125.62

138.24

143.82

150.24

NAME Oct25-2016-smcgdEXPNO 3PROCNO 1Date_ 20161025Time 12.16INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT CDCl3NS 215DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 293.4 KD1 2.00000000 secD11 0.03000000 secTD0 1



cgd-481C13CPD CDCl3

S39

13C NMR spectrum of compound 5i

1H NMR spectrum of compound 5i

200 180 160 140 120 100 80 60 40 20 0 ppm

26.93

29.90

31.45

31.62

62.71

117.06

124.13

125.68

NAME Oct25-2016-smcgdEXPNO 4PROCNO 1Date_ 20161025Time 12.23INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT CDCl3NS 96DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 292.8 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1



cgd-481C13DEPT135 CDCl3

S40

DEPT-135 spectrum of compound 5i

S41

HRMS spectrum of compound 5i

13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm

1.469

1.487

1.504

4.128

4.145

4.163

4.180

5.395

6.857

6.860

6.877

6.899

6.918

6.938

7.294

7.319

7.338

7.399

10.712

3.13

2.40

2.00

1.50

1.96

1.19

NAME Nov10-2016-SMCGDEXPNO 1PROCNO 1Date_ 20161110Time 9.54INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT CDCl3NS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 80.6DW 60.800 usecDE 6.50 usecTE 294.0 KD1 1.00000000 secTD0 1


CGD-488PROTON CDCl310/11/16

S42

1H NMR spectrum of compound 5j

200 180 160 140 120 100 80 60 40 20 0 ppm

14.20

14.87

60.47

64.19

64.59

113.57

114.46

118.54

121.55

143.48

148.18

NAME Nov10-2016-SMCGDEXPNO 2PROCNO 1Date_ 20161110Time 10.32INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT CDCl3NS 476DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 294.9 KD1 2.00000000 secD11 0.03000000 secTD0 1



CGD-488C13CPD CDCl3 10/11/16

S43

13C NMR spectrum of compound 5j

200 180 160 140 120 100 80 60 40 20 0 ppm

14.87

64.19

64.58

113.55

114.45

121.55

NAME Nov10-2016-SMCGDEXPNO 3PROCNO 1Date_ 20161110Time 10.36INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT CDCl3NS 33DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 294.1 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1



CGD-488C13DEPT135 CDCl3 10/11/16

S44

DEPT-135 NMR spectrum of compound 5j

1234567891011121314 ppm

5.374

7.627

7.864

7.885

7.890

13.134

2.21

1.00

1.02

1.04

0.88

NAME Nov11-2016-SMCGDEXPNO 8PROCNO 1Date_ 20161111Time 10.46INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT DMSONS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 57DW 60.800 usecDE 6.50 usecTE 292.7 KD1 1.00000000 secTD0 1



200 180 160 140 120 100 80 60 40 20 0 ppm

64.75

85.42

87.64

110.66

121.33

124.22

129.69

140.29

144.37

152.57

NAME Nov11-2016-SMCGDEXPNO 11PROCNO 1Date_ 20161111Time 11.25INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT DMSONS 512DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 294.2 KD1 2.00000000 secD11 0.03000000 secTD0 1




S45

13C NMR spectrum of compound 5k

1H NMR spectrum of compound 5k

200 180 160 140 120 100 80 60 40 20 0 ppm

64.74

124.22

129.69

144.36

NAME Nov11-2016-SMCGDEXPNO 9PROCNO 1Date_ 20161111Time 10.55INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT DMSONS 139DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 293.3 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1




S46

DEPT-135NMR spectrum of compound 5k

S47

HRMS spectrum of compound 5k

11 10 9 8 7 6 5 4 3 2 1 0 ppm

3.820

5.292

6.976

6.981

7.383

7.388

7.482

3.37

2.22

0.98

1.04

1.00

NAME Nov11-2016-SMCGDEXPNO 35PROCNO 1Date_ 20161112Time 17.01INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT DMSONS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 128DW 60.800 usecDE 6.50 usecTE 292.5 KD1 1.00000000 secTD0 1



200 180 160 140 120 100 80 60 40 20 0 ppm

38.83

39.04

39.25

39.46

39.67

39.87

40.08

55.86

63.82

78.22

78.54

78.75

78.87

110.59

112.72

114.42

116.18

120.17

125.41

141.53

149.40

NAME Nov11-2016-SMCGDEXPNO 36PROCNO 1Date_ 20161112Time 17.30INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT DMSONS 556DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 293.5 KD1 2.00000000 secD11 0.03000000 secTD0 1




S48

13C NMR spectrum of compound 5l

1H NMR spectrum of compound 5l

200 180 160 140 120 100 80 60 40 20 0 ppm

55.85

63.82

114.41

116.18

NAME Nov11-2016-SMCGDEXPNO 37PROCNO 1Date_ 20161112Time 17.42INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT DMSONS 66DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 292.9 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1




S49

DEPT-135 NMR spectrum of compound 5l

13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm

1.662

3.903

5.329

6.900

6.920

6.975

6.995

7.015

7.566

7.585

7.865

9.00

3.20

2.07

0.99

0.93

0.97

0.95

NAME Oct18-2016-SMCGDEXPNO 17PROCNO 1Date_ 20161018Time 12.10INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT CDCl3NS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 181DW 60.800 usecDE 6.50 usecTE 293.8 KD1 1.00000000 secTD0 1



200 180 160 140 120 100 80 60 40 20 0 ppm

27.94

56.04

63.22

85.56

112.96

115.25

115.82

117.60

121.81

124.97

144.32

147.68

148.84

NAME Oct18-2016-SMCGDEXPNO 18PROCNO 1Date_ 20161018Time 12.27INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT CDCl3NS 197DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 295.0 KD1 2.00000000 secD11 0.03000000 secTD0 1



cgd-482C13CPD CDCl3 18/10/16

S50

13C NMR spectrum of compound 6a

1H NMR spectrum of compound 6a

200 180 160 140 120 100 80 60 40 20 0 ppm27.94

56.04

63.23

112.95

115.81

121.82

124.97

NAME Oct18-2016-SMCGDEXPNO 19PROCNO 1Date_ 20161018Time 12.31INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT CDCl3NS 47DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 294.4 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1




S51

DEPT-135 NMR spectrum of compound 6a

S52

HRMS spectrum of compound 6a

10 9 8 7 6 5 4 3 2 1 0 ppm

1.670

3.689

5.244

7.193

7.198

7.200

7.214

7.215

7.220

7.221

7.264

7.265

7.867

7.869

7.923

7.928

9.00

1.95

0.93

0.81

0.85

0.69

NAME Aug03-2016-SMCGDEXPNO 11PROCNO 1Date_ 20160803Time 11.16INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT CDCl3NS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 256DW 60.800 usecDE 6.50 usecTE 292.2 KD1 1.00000000 secTD0 1



200 180 160 140 120 100 80 60 40 20 0 ppm

27.95

62.95

76.72

77.04

77.35

85.82

115.06

118.13

118.83

123.47

125.17

127.19

130.56

146.71

153.50

NAME Aug03-2016-SMCGDEXPNO 12PROCNO 1Date_ 20160803Time 11.28INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT CDCl3NS 105DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 293.2 KD1 2.00000000 secD11 0.03000000 secTD0 1



CGD-468C13CPD CDCl3 03/08/16

S53



200 180 160 140 120 100 80 60 40 20 0 ppm

27.95

62.95

118.83

123.47

125.18

130.56

NAME Aug03-2016-SMCGDEXPNO 30PROCNO 1Date_ 20160803Time 17.56INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT CDCl3NS 237DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 292.7 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1



cgd-468C13DEPT135 CDCl3 03/08/16

S54


S55


10 9 8 7 6 5 4 3 2 1 0 ppm

2.678

2.683

2.692

2.696

2.701

2.707

2.711

2.720

2.725

2.729

2.738

3.187

3.215

3.244

4.142

4.155

4.169

4.183

4.498

4.505

4.516

4.523

4.541

4.549

4.559

4.567

4.709

4.713

4.718

4.752

4.757

4.761

5.500

5.517

7.128

7.150

7.479

7.481

7.499

7.517

7.519

7.665

7.667

7.685

7.688

7.703

7.706

7.780

7.803

7.866

7.887

8.673

8.694

1.01

1.06

1.08

1.04

1.09

1.01

0.87

0.95

0.97

0.97

0.94

1.00


S56


200 180 160 140 120 100 80 60 40 20 0 ppm

29.03

64.98

78.42

82.52

110.40

118.61

123.87

124.19

127.22

128.53

129.61

129.99

133.47

153.55

CGD-498C13CPD CDCl3 27/02/17

S57


200 180 160 140 120 100 80 60 40 20 0 ppm29.0

2

64.9

7

78.4

282.5

1

118.

61123.

86124.

19126.

40127.

22128.

53129.

99

CGD-498C13DEPT135 CDCl3 27/02/17

S58


ppm

9 8 7 6 5 4 3 2 1 0 ppm

9

8

7

6

5

4

3

2

1

0

cgd-498 COSYGPSW CDCl3

S59

COSY NMR spectrum of compound 8b

ppm

9 8 7 6 5 4 3 2 1 0 ppm

140

120

100

80

60

40

20

0

cgd-498 HSQCGP CDCl3

S60

HSQC NMR spectrum of compound 8b

S61


12 11 10 9 8 7 6 5 4 3 2 1 0 ppm

1.182

1.252

1.468

1.483

1.498

1.618

1.634

1.797

3.849

3.864

3.880

4.147

5.346

6.662

6.836

6.856

6.886

6.905

6.927

6.950

6.970

7.187

7.203

7.223

7.318

7.336

7.353

7.589

7.607

7.773

7.790

6.43

4.59

2.38

2.24

2.46

1.98

2.00

1.01

1.07

2.32

2.11

1.15

0.93

1.30

0.64

NAME Sep16-2015-smcgdEXPNO 6PROCNO 1Date_ 20150916Time 12.21INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zg30TD 65536SOLVENT CDCl3NS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 362DW 60.800 usecDE 6.50 usecTE 301.5 KD1 1.00000000 secTD0 1



S62


200 180 160 140 120 100 80 60 40 20 0 ppm

25.93

26.03

29.09

29.15

29.23

29.41

45.87

52.11

68.61

69.02

74.64

76.68

77.00

77.31

78.00

111.99

112.58

113.32

119.63

120.01

120.49

122.02

125.09

128.26

129.48

131.86

133.75

135.80

159.01

161.58

165.47

189.79

NAME Sep16-2015-smcgdEXPNO 13PROCNO 1Date_ 20150916Time 15.38INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG zgpg30TD 65536SOLVENT CDCl3NS 1024DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 305.0 KD1 2.00000000 secD11 0.03000000 secTD0 1



cgd-439C13CPD CDCl3 16/09/15

200 180 160 140 120 100 80 60 40 20 0 ppm

25.93

26.04

29.09

29.15

29.23

29.42

45.87

52.12

68.59

69.00

112.58

113.29

120.01

120.49

128.17

128.25

129.49

130.70

131.87

133.77

135.82

189.82

NAME Sep16-2015-smcgdEXPNO 14PROCNO 1Date_ 20150916Time 15.54INSTRUM spectPROBHD 5 mm PABBO BB-PULPROG dept135TD 65536SOLVENT CDCl3NS 256DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 2050DW 20.800 usecDE 6.50 usecTE 303.8 KCNST2 145.0000000D1 2.00000000 secD2 0.00344828 secD12 0.00002000 secTD0 1




S63



S64


13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm

1.236

1.306

1.522

1.537

1.552

1.672

1.687

1.850

3.903

3.918

3.934

4.200

5.400

6.716

6.890

6.910

6.940

6.959

6.981

7.004

7.024

7.241

7.257

7.277

7.372

7.389

7.407

7.643

7.661

7.827

7.843

11.074

11.093

11.128

11.169

11.191

11.215

11.233

11.490

8.28

4.24

2.50

2.20

2.40

2.00

1.99

0.95

3.39

2.23

1.20

0.99

1.33

0.65

cgdsr-27rPROTON CDCl3 27/09/15

S65

1H NMR spectrum of compound 12c

200 180 160 140 120 100 80 60 40 20 0 ppm

27.13

27.24

30.30

30.36

30.44

30.62

47.08

53.32

69.82

70.23

75.85

79.21

113.20

113.79

114.53

120.84

121.22

121.70

123.23

126.30

129.47

130.69

133.07

134.96

137.01

160.22

162.79

166.67

191.00

cgdsr-27rC13CPD CDCl3 27/09/15

(2) Solid-state arrangement of compound 6b

The crystal packing pattern (Figures 1-6, see supporting information) of compound 6b

divulged a number of close intermolecular links between the molecules, which are associated

as dimer via intermolecular two C-H---O and a C-H---Cl hydrogen bonding interactions that

are described as given below:

For C(2)–H(2)---O(1): H(2)---O(1) = 2.704 Å and < C(2)–H(2)---O(1) = 138.24o

For C(9)-H(9b)---O(1): H(9b)---O(1) = 2.458 Å and < C(9)-H(9b)---O(1) = 152.90o

For C(3)-H(3)···Cl(1): H(3)···Cl(1) = 2.781 Å and < C(3)-H(3)···Cl(1) = 169.83 o

S66

13C NMR spectrum of compound 12c

Crystallographic Information of compound 6b

Bond precision: C-C = 0.0022 A Wavelength=0.71073

Cell: a=7.0335(10) b=16.009(2) c=13.6812(18)

alpha=90 beta=100.030(3) gamma=90

Temperature: 296 K

Calculated Reported

Volume 1517.0(3) 1516.9(4)

Space group P 21/n P 21/n

Hall group -P 2yn -P 2yn

Moiety formula C15 H15 Cl N2 O3 C15 H15 Cl N2 O3

Sum formula C15 H15 Cl N2 O3 C15 H15 Cl N2 O3

Mr 306.74 306.74

Dx,g cm-3 1.343 4.654

Z 4 4

Mu (mm-1) 0.263 2.956

F000 640.0 2115.0

F000’ 640.87

h,k,lmax 9,21,18 9,21,18

Nref 3835 3823

Tmin,Tmax

Tmin’

Correction method= Not given

Data completeness= 0.997 Theta(max)= 28.461

R(reflections)= 0.0389( 2916) wR2(reflections)= 0.1138( 3823)

S = 0.827 Npar= 193

S67

Figure 1. A Unit cell contains two asymmetric units of 6b with opposite orientation of phenyl ring and tert-butyl group with each other

Figure 2. A partial packing view for 6b showing the chain extending along c-axis of the unit cell through C(3)-H(3)···Cl(1) and C(9)-H(9b)---O(1) hydrogen bonding interactions. Green coloured lines indicate hydrogen bonds.

S68

Figure 3. The molecular arrangement of compound 6b viewed through b-axis.

Figure 4. Zig-zag arrangement of molecules of compound 6b viewed along c*-axis.

S69

Figure 5. Molecular arrangement of compound 6b viewed through b-axis.

Figure 6. An overview of interactions of atoms of 6b

-------------

S70

Solid state arrangement of compound 8b

The solid-state arrangements (Figures 7-11, see supporting information) of compound 8b divulged with three C-H/π interactions. The C-H/π interaction parameters are given below:

1. C(13)-H(13)---Cg(1); H(13)---Cg(1) = 2.639 Å and <C(13)-H(13)---C(9) = 150.89°

2. C(5)-H(5)---Cg(2); H(5)---Cg(2) = 3.220Å and <C(5)-H(5)---Cg(2) = 154.18°

3. C(11)-H(11)---Cg(3); H(11)---Cg(3) = 2.766 Å and <C(11)-H(11)---Cg(3) = 154.25°

Crystallographic information of compound 8b

Bond precision: C-C = 0.0038 A Wavelength=0.71073

Cell: a=5.1418(3) b=8.3699(4) c=25.9032(14)

alpha=90 beta=90 gamma=90

Temperature: 293 K

Calculated Reported

Volume 1114.78(10) 1114.78(10)

Space group P 21 21 21 P 21 21 21

Hall group P 2ac 2ab P 2ac 2ab

Moiety formula C14 H12 N2 O C14 H12 N2 O

Sum formula C14 H12 N2 O C14 H12 N2 O

Mr 224.26 224.26

Dx,g cm-3 1.336 1.336

Z 4 4

Mu (mm-1) 0.086 0.086

F000 472.0 472.0

F000’ 472.18

h,k,lmax 7,12,37 7,12,35

Nref 3623[ 2126] 3305

Tmin,Tmax 0.977,0.985 0.756,0.835

Tmin’ 0.975

Correction method= # Reported T Limits: Tmin=0.756 Tmax=0.835

AbsCorr = MULTI-SCAN

Data completeness= 1.55/0.91 Theta(max)= 31.162

R(reflections)= 0.0524( 2180) wR2(reflections)= 0.1443( 3305)

S = 1.037 Npar= 154

S71

Figure 7. A unit cell with asymmetric unit with labelling viewed through b-axis of 8b

Figure 8. A partial packing view of 8b showing hydrogen bonding and C-H-π interaction (blue coloured line) in solid state arrangement

Figure 9. Zig-zag arrangement of molecules of 8b viewed through b-axis

S72

Figure 10. Layered arrangement of molecules of 8b viewed via b-axis

Figure 11. An overview of interactions of atoms of 8b

=============

S73

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