7KLV - rsc.org · S1 Supporting information for p-Toluenesulfonic acid catalyzed single pot...
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S1 Supporting information for p-Toluenesulfonic acid catalyzed single pot synthesis of tetracyclic 1,2-Dihydroquinolines: a metal free approach Anil K. Hajare a , Arun R. Jagdale a , G. Gautham Shenoy b and Neelima Sinha a, a Novel Drug Discovery & Development, Lupin Limited, 1 st Floor, Genesis Square Building, Hinjewadi, Phase-2, Village - Man, Tal. Mulshi, Dist. - Pune, Maharashtra, India, 411057. b Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India, 576104. Email: [email protected] Table Of Contents (1) General Procedure and characterisation data…………………S2-S7 (2) Copies of 1 H and 13 C NMR spectra………………………… S8-S26 Electronic Supplementary Material (ESI) for New Journal of Chemistry. This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2016
Transcript of 7KLV - rsc.org · S1 Supporting information for p-Toluenesulfonic acid catalyzed single pot...
S1
Supporting information for
p-Toluenesulfonic acid catalyzed single pot synthesis of tetracyclic 1,2-Dihydroquinolines: a metal free approach
Anil K. Hajare a, Arun R. Jagdale a, G. Gautham Shenoy b and Neelima Sinhaa, a Novel Drug Discovery & Development, Lupin Limited, 1st Floor, Genesis Square Building, Hinjewadi, Phase-2, Village - Man, Tal. Mulshi, Dist. - Pune, Maharashtra, India, 411057.b Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India, 576104.
Email: [email protected]
Table Of Contents
(1) General Procedure and characterisation data…………………S2-S7(2) Copies of 1H and 13C NMR spectra………………………… S8-S26
Electronic Supplementary Material (ESI) for New Journal of Chemistry.This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2016
S2
General:
Commercially available reagents and solvents were used without further purification. 1H
and 13C NMR experiments were performed on a Bruker AVANCE 400 MHz instrument,
operating at 400 MHz for protons and 100 MHz for carbon nuclei. Data for 1H NMR spectra are
reported as follows: chemical shift (δ) in parts per million (multiplicity, coupling constant (Hz),
integration). Data for 1H NMR spectra are referenced to the center line of CDCl3 (δ 7.26) as the
internal standard. Data for 13C NMR spectra are referenced to the center line of CDCl3 (δ 77.0).
High-resolution mass spectra were obtained on a mass spectrometer in ESI or EI mode using a
TOF mass analyzer. Reaction progress was monitored by thin layer chromatography (TLC,
Merck, Inc., silica gel 60 F254), visualized under UV light, and plates were developed using
iodine. Flash chromatography was performed using silica gel 100 – 200 mesh. Melting points
were determined using Buchi apparatus and are uncorrected.
General Procedure for the p-TSA-Catalyzed Synthesis of 2,2,4-Trialkyl-1,2-
dihydroquinolines 8a−l (Method A). In a reaction vial containing a magnetic stir bar, was taken
a mixture of aniline 6a−l (1.0 molar equiv), ketone 7 (5.0 molar equiv) and p-toluene sulfonic
acid (0.2 molar equiv) in DMF (1 mL per mmol of substrate). Reaction vial was capped and
stirred at the specified temperature (140°C) until complete disappearance of the starting material
was observed by TLC. The reaction was transferred to a separatory funnel containing water and
extracted with diethyl ether (3 × 30 mL). The combined organic extracts were dried over
Na2SO4, and solvent was removed in vacuo. The residue was purified by flash column
chromatography on silica gel (gradient elution with EtOAc and hexanes).
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General Procedure for the p-TSA-Catalyzed Synthesis of 2,2,4-Trialkyl-1,2-
dihydroquinolines 10a−g (Method B). In a reaction vial containing a magnetic stir bar, was
taken a mixture of aniline (1.0 molar equiv), p-toluene sulfonic acid (0.2 molar equiv) in Ketone
(2 mL per mmol of substrate) as a solvent. Reaction vial was capped and stirred at the specified
temperature (100°C) until complete disappearance of starting material was observed by TLC.
The solvent was evaporated under reduced pressure and residue was diluted with diethyl ether 50
mL., transferred to a separatory funnel containing water and extracted with diethyl ether (3 × 30
mL). The combined organic extracts were dried over Na2SO4, and solvent was removed in
vacuo. The residue was purified by flash column chromatography on silica gel (gradient elution
with EtOAc and hexanes).
1,2,3,5-Tetrahydrospiro[cyclopenta[c]quinoline-4,1'-cyclopentane] (8a). Pale yellow solid;
yield: 45%; mp: 83-84 °C; 1H NMR (400 MHz, CDCl3) δ 6.96 (td, J = 7.6, 1.2 Hz, 1H), 6.90 (dd,
J = 7.6, 1.2 Hz, 1H), 6.63 (td, J = 7.6, 1.2 Hz, 1H), 6.46 (dd, J = 7.6, 1.2 Hz, 1H), 3.93 (br s, 1H),
2.72–2.63 (m, 2H), 2.58–2.47 (m, 2H), 2.10–1.98 (m, 2H), 1.97–1.85 (m, 2H), 1.84 – 1.64 (m,
6H); 13C-NMR (100 MHz, CDCl3) δ 142.6, 138.7, 132.1, 127.5, 123.3, 120.4, 117.1, 112.2, 65.1,
39.6, 32.2, 31.2, 23.9, 22.4; HRMS (ESI) calcd. for C16H19N [M+H]+ m/z = 225.1517, found
225.1513.
8-Methyl-1,2,3,5-tetrahydrospiro[cyclopenta[c]quinoline-4,1'-cyclopentane] (8b) White
solid; yield: 46%; mp: 82-84 °C; 1H NMR (400 MHz, DMSO-d6) δ 6.64 (d, J = 8.0, 1H), 6.55 (s,
1H), 6.41 (d, J = 8.0 Hz, 1H), 5.61 (br s, 1H), 2.55–2.40 (m, 4H), 2.11 (s, 3H), 1.92 (p, J = 7.2
Hz, 2H), 1.82–1.70 (m, 4H), 1.65–1.57 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 140.35 , 139.20
, 132.19 , 127.89 , 126.28 , 123.92 , 112.33 , 77.23 , 65.05 , 39.43 , 32.23 , 31.22 , 23.96 , 22.47 ,
20.72; HRMS (ESI) calcd. for C17H21N [M+H]+ m/z = 239.1674, found 239.1671.
S4
8-Chloro-1,2,3,5-tetrahydrospiro[cyclopenta[c]quinoline-4,1'-cyclopentane] (8c) White
solid; yield: 21%; mp: 106-108 °C; 1H NMR (400 MHz, DMSO-d6) δ 6.82 (dd, J = 8.4, 2.4 Hz,
1H), 6.69 (d, J = 2.4 Hz, 1H), 6.49 (d, J = 8.4 Hz, 1H), 6.06 (br s, 1H), 2.50–2.42 (m, 4H), 1.92
(quint, J = 7.6 Hz, 2H), 1.87–1.70 (m, 4H), 1.67–1.48 (m, 4H); 13C NMR (100MHz, DMSO-d6)
δ 142.3, 139.9, 130.1, 126.7, 122.0, 120.3, 118.3, 112.8, 64.2, 40.4, 31.8, 30.5, 23.8, 21.7;
HRMS (ESI) calcd. for C16H18ClN [M+H]+ m/z = 259.1128, found 259.1128.
7-Methoxy-1,2,3,5-tetrahydrospiro[cyclopenta[c]quinoline-4,1'-cyclopentane] (8e) White
solid; yield: 76%; mp: 108-110 °C; 1H NMR (400 MHz, CDCl3) δ 6.80 (d, J = 8.0 Hz, 1H), 6.19
(dd, J = 8.0, 2.4 Hz, 1H), 6.05 (d, J = 2.4 Hz, 1H), 3.97 (br s, 1H), 3.76 (s, 3H), 2.69–2.59 (m,
2H), 2.55–2.45 (m, 2H), 2.05–1.97 (m, 2H), 1.92–1.84 (m, 2H), 1.80–1.64 (m, 6H); 13C-NMR
(100 MHz, CDCl3) δ 159.6, 143.9, 135.9, 131.7, 124.1, 114.2, 102.0, 98.3, 65.1, 55.1, 39.8, 32.0,
31.2, 23.9, 22.4; HRMS (ESI) calcd. for C17H21NO [M+H]+ m/z = 255.1623, found 255.1621.
7-Methyl-1,2,3,5-tetrahydrospiro[cyclopenta[c]quinoline-4,1'-cyclopentane] (8f) White
solid; yield: 73%; mp: 77-79 °C; 1H NMR (400 MHz, DMSO-d6) δ 6.60 (d, J = 7.6 Hz, 1H), 6.32
(s, 1H), 6.22 (d, J = 7.6Hz, 1H), 5.73 (br s, 1H), 2.50–2.41 (m, 4H), 2.11 (s, 3H), 1.91 (quint, J =
7.6 Hz, 2H), 1.84–1.70 (m, 4H), 1.65–1.49 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 142.5,
137.6, 137.3, 132.0, 123.1, 117.9, 112.8, 65.1, 39.7, 32.1, 31.2, 23.9, 22.4, 21.5; HRMS (ESI)
calcd. for C17H21N [M+H]+ m/z = 239.1674, found 239.1669.
7-Chloro-1,2,3,5-tetrahydrospiro[cyclopenta[c]quinoline-4,1'-cyclopentane] (8g) White
solid; yield: 30%; mp: 68-69 °C; 1H NMR (400 MHz, CDCl3) δ 6.77 (d, J = 8.0 Hz, 1H), 6.56
(dd, J = 8.0, 2.0 Hz, 1H), 6.43 (d, J = 2.0 Hz, 1H), 3.97 (br s, 1H), 2.68–2.59 (m, 2H), 2.56–2.47
(m, 2H), 2.03 (quint, J = 7.6 Hz, 2H), 1.96–1.85 (m, 2H), 1.84–1.64 (m, 6H); 13C NMR (100
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MHz, CDCl3) δ 143.6, 138.9, 132.5, 131.4, 124.1, 118.8, 116.8, 111.7, 65.2, 40.1, 32.2, 31.1 ,
23.9, 22.3; HRMS (ESI) calcd. for C16H18ClN [M+H]+ m/z = 259.1128, found 259.1123.
N-(1,2,3,5-tetrahydrospiro[cyclopenta[c]quinoline-4,1'-cyclopentan]-7-yl)acetamide (8h)
Yellow solid; yield: 76%; mp 236−238 °C; 1H NMR (400 MHz, DMSO-d6) δ 9.57 (br s, 1H),
6.98 (d, J = 2.0 Hz, 1H), 6.61 (d, J = 8.0 Hz, 1H), 6.47 (dd, J = 8.0, 2.0 Hz, 1H), 5.94 (br s, 1H),
2.50–2.39 (m, 4H), 1.99 (s, 3H), 1.90 (quint, J = 7.2 Hz, 2H), 1.83–1.74 (m, 4H), 1.64–1.49 (m,
4H); 13C-NMR (100 MHz, DMSO-d6) δ 168.2, 144.2, 139.2, 136.9, 131.0, 123.1, 115.1, 106.7,
103.0, 64.6, 40.8, 32.1, 31.0, 24.5, 24.4, 22.3; HRMS (ESI) calcd. for C18H22N2O [M+H]+ m/z =
282.1732, found 282.1728.
6-Methoxy-1,2,3,5-tetrahydrospiro[cyclopenta[c]quinoline-4,1'-cyclopentane] (8i) Pale
yellow solid; yield: 20%; mp 95-96 °C; 1H NMR (400 MHz, CDCl3) δ 6.69–6.54 (m, 3H), 4.47
(br s, 1H), 3.85 (s, 3H), 2.71–2.64 (m, 2H), 2.57– 2.50 (m, 2H), 2.03 (quint, J = 7.2 Hz, 2H),
1.94–1.86 (m, 2H), 1.83–1.75 (m, 4H), 1.72–1.65 (m, 2H); 13C-NMR (100 MHz, CDCl3) δ
145.2, 138.6, 132.1, 132.1, 120.3, 116.1, 115.7, 109.0, 64.6, 55.6, 40.0, 32.2, 31.4, 23.9, 22.4;
HRMS (ESI) calcd. for C17H21NO [M+H]+ m/z = 255.1623, found 255.1625.
6-Methyl-1,2,3,5-tetrahydrospiro[cyclopenta[c]quinoline-4,1'-cyclopentane] (8j) White
solid; yield: 12%; mp 69-70 °C; 1H-NMR (400 MHz, CDCl3) δ 6.88 (d, J = 7.6 Hz, 1H), 6.82 (d,
J = 7.6 Hz, 1H), 6.58 (t, J = 7.6 Hz, 1H), 3.83 (br s, 1H), 2.73–2.65 (m, 2H), 2.59–2.50 (m, 2H),
2.12 (s, 3H), 2.04 (quint, J = 7.2Hz, 2H), 1.97–1.87 (m, 2H), 1.85– 1.69 (m, 6H); 13C-NMR (100
MHz, CDCl3) δ 140.5, 138.2, 132.5, 128.9, 121.4, 119.7, 119.0, 116.4, 65.0, 40.0, 32.2, 31.4,
23.8, 22.5, 17.0; HRMS (ESI) calcd. for C17H21N [M+H]+ m/z = 239.1674, found 239.1669.
S6
7',8',9',10'-tetrahydro-5'H-spiro[cyclohexane-1,6'-phenanthridine] (8k) Oil; yield: 40%;
1H NMR (400 MHz, CDCl3) δ 7.09 (dd, J = 7.6, 1.2 Hz, 1H), 7.00 (td, J = 7.6, 1.2 Hz, 1H), 6.71
(td, J = 7.6, 1.2 Hz, 1H), 6.59 (dd, J = 7.6, 1.2 Hz, 1H), 4.43 (br s, 1H), 2.43–2.37 (m, 2H), 2.17–
2.11 (m, 2H), 1.82–1.66 (m, 8H), 1.65 –1.59 (m, 2H), 1.56–1.41 (m, 4H); 13C-NMR (100 MHz,
CDCl3) δ 142.0, 135.9, 127.1, 125.2, 124.3, 122.1, 117.9, 113.6, 77.1, 54.6, 32.4, 25.4, 25.2,
24.9, 23.1, 22.4, 21.2; HRMS (ESI) calcd. for C18H23N [M+H]+ m/z = 253.1830, found 253.1831.
3'-methoxy-7',8',9',10'-tetrahydro-5'H-spiro[cyclohexane-1,6'-phenanthridine] (8l) White
solid; yield: 63%; mp 102-103 °C; 1H NMR (400 MHz, CDCl3) δ 7.00 (d, J = 8.4 Hz, 1H), 6.27
(dd, J = 8.4, 2.4 Hz, 1H), 6.18 (d, J = 2.4 Hz, 1H), 4.42 (br s, 1H), 3.79 (s, 3H), 2.41–2.33 (m,
2H), 2.16–2.09 (m, 2H), 1.80–1.41 (m, 14H); 13C NMR (100 MHz, CDCl3) δ 159.2, 143.4,
133.2, 124.9, 123.1, 118.0, 102.9, 99.4, 55.1, 54.7, 32.5, 25.4, 25.3, 24.7, 23.2, 22.5, 21.1;
HRMS (ESI) calcd. for C19H25NO [M+H]+ m/z = 283.1936, found 283.1934.
2,2,4-Trimethyl-1,2-dihydroquinoline (10a) Oil; yield: 43%; 1H NMR (400 MHz, CDCl3) δ
7.06 (dd, J = 7.6, 1.2 Hz, 1H), 6.99 (td, J = 7.6, 1.2 Hz, 1H), 6.64 (td, J = 7.6, 1.2 Hz, 1H), 6.45
(dd, J = 7.6, 1.2 Hz, 1H), 5.33 (q, J = 1.2 Hz, 1H), 3.74 (br s, 1H), 1.99 (d, J = 1.2 Hz, 3H), 1.28
(s, 6H); 13C-NMR (100 MHz, CDCl3) δ 143.2, 128.6, 128.39, 128.36, 123.6, 121.6, 117.2,
113.0, 51.8, 31.0, 18.6; HRMS (ESI) calcd. for C12H15N [M+H]+ m/z = 173.1204, found
173.1208.
7-Methoxy-2,2,4-trimethyl-1,2-dihydroquinoline (10b) White solid; yield: 56%; mp 68−69
°C; 1H NMR (400 MHz, CDCl3) δ 6.98 (d, J = 8.4 Hz, 1H), 6.22 (dd, J = 8.4, 2.4 Hz, 1H), 6.06
(d, J = 2.4 Hz, 1H), 5.20 (s, 1H), 3.78 (br s, 1H), 3.75 (s, 3H), 1.96 (s, 3H), 1.27 (s, 6H); 13C-
S7
NMR (100 MHz, CDCl3) δ 160.2, 144.7, 130.6, 128.2, 126.2, 124.7, 115.3, 102.3, 98.6, 55.1,
51.9, 31.1, 18.7; HRMS (ESI) calcd. for C13H17NO [M+H]+ m/z = 203.1310, found 203.1306.
2,2,4,7-tetramethyl-1,2-dihydroquinoline (10c) Oil; yield: 52%; 1H NMR (400 MHz, CDCl3) δ
7.00 (d, J = 7.6 Hz, 1H), 6.51 (dd, J = 7.6, 1.6 Hz, 1H), 6.33 (d, J = 1.6 Hz, 1H), 5.29 (d, J = 1.6
Hz, 1H), 3.69 (br s, 1H), 2.27 (s, 3H), 2.01 (d, J = 1.6 Hz, 3H), 1.31 (s, 6H); 13C-NMR (100
MHz, CDCl3) δ 143.23, 138.32, 128.53, 127.46, 123.60, 119.18, 118.10, 113.68, 51.86, 31.04,
21.45, 18.68; HRMS (ESI) calcd. for C13H17N [M+H]+ m/z = 187.1361, found 187.1361.
7-chloro-2,2,4-trimethyl-1,2-dihydroquinoline (10d) Oil; yield: 45%; 1H NMR (400 MHz,
CDCl3) δ 6.97 (d, J = 8.0 Hz, 1H), 6.61 (dd, J = 8.0, 2.0 Hz, 1H), 6.46 (d, J = 2.0 Hz, 1H), 5.33
(d, J = 1.6 Hz, 1H), 3.92 (s, 1H), 1.98 (s, 3H), 1.30 (s, 6H); 13C-NMR (100 MHz, CDCl3) δ
144.22, 133.54, 128.44, 127.84, 124.67, 120.06, 116.95, 112.47, 52.15, 31.10, 18.57; HRMS
(ESI) calcd. for C12H14ClN [M+H]+ m/z = 207.0815, found 207.0817.
2,4-diethyl-2-methyl-1,2-dihydroquinoline (10e) Oil; yield: 45%; 1H NMR (400 MHz, CDCl3)
δ 7.13 (dd, J = 7.6, 1.2 Hz, 1H), 7.00 (td, J = 7.6, 1.2 Hz, 1H), 6.64 (td, J = 7.6, 1.2 Hz, 1H), 6.47
(dd, J = 8.0, 1.2 Hz, 1H), 5.24 (d, J = 1.2 Hz, 1H), 3.63 (br s, 1H), 2.43 (q, J = 7.2 Hz, 2H), 1.61
– 1.48 (m, 2H), 1.27 (s, 3H), 1.20 (t, J = 7.2 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H); 13C-NMR (100
MHz, CDCl3) δ 143.96, 134.80, 128.20, 125.11, 123.22, 120.60, 116.70, 112.83, 54.61, 36.51,
29.45, 24.62, 12.94, 8.59; HRMS (ESI) calcd. for C14H19N [M+H]+ m/z = 201.1517, found
201.1518.
2,4-Diethyl-7-methoxy-2-methyl-1,2-dihydroquinoline (10f) White solid; yield: 60%; mp
60−61 °C; 1H NMR (400 MHz, CDCl3) δ 7.03 (d, J = 8.4 Hz, 1H), 6.20 (dd, J = 8.4, 2.4 Hz, 1H),
6.06 (d, J = 2.4 Hz, 1H), 5.12 (t, J = 1.6 Hz, 1H), 3.78 (br s, 1H), 3.77 (s, 3H), 2.39 (q, J = 7.2
S8
Hz, 2H), 1.58–1.48 (m, 2H), 1.25 (s, 3H), 1.18 (t, J = 7.6 Hz, 3H), 0.93 (t, J = 7.6 Hz, 3H); 13C-
NMR (100 MHz, CDCl3) δ 160.0, 145.4, 134.5, 124.2, 122.6, 114.3, 101.8, 98.4, 55.0, 54.8,
36.5, 29.5, 24.7, 12.9, 8.5; HRMS (ESI) calcd. for C15H21NO [M+H]+ m/z = 231.1623, found
231.1622.
2,4-diethyl-2,7-dimethyl-1,2-dihydroquinoline (10g) Oil; yield: 45%; 1H NMR (400 MHz,
CDCl3) δ 7.01 (d, J = 7.6 Hz, 1H), 6.46 (d, J = 7.6 Hz, 1H), 6.33 (s, 1H), 5.18 (s, 1H), 3.87 (br s,
1H), 2.41 (q, J = 7.6 Hz, 2H), 2.24 (s, 3H), 1.60 – 1.47 (m, 2H), 1.25 (s, 3H), 1.18 (t, J = 7.6 Hz,
3H), 0.94 (t, J = 7.6 Hz, 3H); 13C-NMR (100 MHz, CDCl3) δ 143.94, 138.11, 134.75, 124.13,
123.16, 118.12, 117.56, 113.46, 54.61, 36.50, 29.47, 24.67, 21.37, 13.00, 8.61; HRMS (ESI)
calcd. for C14H19N [M+H]+ m/z = 215.1674, found 215.1674.
S9
NH8a
NH8a
1H and 13C spectra of compound 8a
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
6.47
2.16
2.31
2.15
2.17
0.98
0.95
0.99
0.98
1.00
1.66
1.68
1.70
1.73
1.75
1.77
1.79
1.85
1.85
1.88
1.89
1.92
1.98
2.00
2.02
2.49
2.51
2.53
2.64
2.64
2.66
2.67
2.68
2.68
3.91
6.43
6.43
6.45
6.45
6.59
6.59
6.61
6.61
6.63
6.63
6.87
6.87
6.89
6.89
6.92
6.92
6.94
6.94
6.95
6.96
7.26
0102030405060708090100110120130140150160f1 (ppm)
22.3
923
.94
31.1
632
.18
39.8
5
65.0
8
112.
15
117.
1312
0.38
123.
28
127.
49
132.
11
138.
73
142.
59
S10
NH8b
NH8b
1H and 13C spectra of compound 8b
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
4.03
4.03
2.03
3.00
4.01
1.00
1.00
1.00
1.00
1.51
1.53
1.60
1.61
1.72
1.77
1.80
1.88
1.90
1.92
1.94
1.95
2.11
2.43
2.45
2.46
5.61
6.40
6.42
6.55
6.63
6.65
05101520253035404550556065707580859095100105110115120125130135140145f1 (ppm)
20.7
222
.47
23.9
6
31.2
232
.23
39.4
3
65.0
5
112.
3311
3.48
120.
6512
3.92
126.
2812
7.89
129.
7413
2.19
139.
2014
0.35
S11
NH8c
Cl
NH8c
Cl
1H and 13C spectra of compound 8c
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
4.09
4.07
2.08
3.87
1.00
1.03
1.02
1.01
1.55
1.62
1.65
1.73
1.76
1.79
1.81
1.85
1.88
1.90
1.92
1.94
1.96
2.44
2.46
2.48
6.06
6.48
6.50
6.68
6.69
6.81
6.81
6.83
6.84
0102030405060708090100110120130140150f1 (ppm)
21.7
423
.83
30.4
531
.79
40.3
8
64.2
4
112.
78
118.
3212
0.33
121.
98
126.
71
130.
10
139.
93
142.
26
S12
NH8e
O
NH8e
O
1H and 13C spectra of compound 8e
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
6.11
2.07
2.17
2.14
2.09
3.13
1.03
1.00
1.00
1.00
1.69
1.74
1.76
1.86
1.88
1.90
1.92
1.98
1.99
2.01
2.03
2.05
2.48
2.50
2.51
2.62
2.63
2.66
3.76
3.97
6.04
6.05
6.17
6.18
6.19
6.20
6.79
6.81
0102030405060708090100110120130140150160170f1 (ppm)
22.3
823
.89
31.2
332
.04
39.8
0
55.1
2
65.1
2
98.2
5
101.
99
114.
23
124.
08
131.
69
135.
87
143.
88
159.
62
S13
NH8f
NH8f
1H and 13C spectra of compound 8f
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)
4.00
4.04
2.02
2.98
4.10
0.99
0.98
1.00
1.01
1.54
1.59
1.63
1.73
1.77
1.78
1.82
1.87
1.89
1.91
1.93
1.95
2.11
2.42
2.44
2.45
2.49
5.73
6.21
6.23
6.32
6.59
6.61
05101520253035404550556065707580859095100105110115120125130135140145150f1 (ppm)
21.5
122
.38
23.8
6
31.1
632
.08
39.6
6
65.0
5
112.
87
117.
90
123.
14
132.
03
137.
3113
7.55
142.
54
1H and 13C spectra of compound 8g
S14
NH8g
Cl
NH8g
Cl
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
6.16
2.16
2.22
2.11
2.15
1.02
1.00
0.97
1.05
1.70
1.74
1.75
1.77
1.87
1.89
1.91
1.93
1.99
2.01
2.03
2.04
2.06
2.49
2.51
2.53
2.61
2.64
2.66
3.97
6.43
6.43
6.55
6.55
6.57
6.57
6.76
6.78
0102030405060708090100110120130140150f1 (ppm)
22.2
823
.92
31.1
232
.20
40.0
6
65.2
4
111.
71
116.
7711
8.82
124.
14
131.
3713
2.50
138.
91
143.
62
1H and 13C spectra of compound 8h
S15
NH8h
NH
O
NH8h
NH
O
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
4.13
4.07
2.17
3.00
4.09
0.99
1.01
1.02
1.02
1.00
1.52
1.60
1.61
1.78
1.82
1.87
1.89
1.90
1.92
1.94
1.98
5.94
6.46
6.47
6.48
6.49
6.60
6.62
6.98
6.99
9.57
0102030405060708090100110120130140150160170180f1 (ppm)
22.3
224
.37
24.5
227
.96
31.0
332
.11
40.8
0
64.5
8
103.
01
106.
77
115.
05
123.
11
131.
02
136.
8513
9.15
144.
19
168.
14
S16
NH8i
O
NH8i
O
1H and 13C spectra of compound 8i
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
2.08
4.07
2.04
2.14
2.03
2.06
3.00
1.02
3.04
1.63
1.69
1.71
1.78
1.80
1.89
1.91
2.00
2.01
2.03
2.05
2.07
2.52
2.54
2.56
2.66
2.68
2.70
3.85
4.47
6.56
6.57
6.59
6.65
6.66
0102030405060708090100110120130140150f1 (ppm)
22.4
323
.92
31.4
032
.19
40.0
4
55.6
1
64.6
3
109.
04
115.
7311
6.08
120.
29
132.
0713
2.12
138.
65
145.
18
S17
NH8j
CH3
NH8j
CH3
1H and 13C spectra of compound 8j
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
6.07
2.09
2.13
3.02
2.05
2.05
1.00
0.99
1.00
1.02
1.36
1.68
1.69
1.70
1.73
1.74
1.77
1.81
1.88
1.89
1.91
1.92
1.98
2.00
2.02
2.04
2.06
2.10
2.50
2.52
2.54
2.65
2.65
2.66
2.68
2.68
3.81
4.49
6.54
6.55
6.57
6.79
6.81
6.85
6.86
7.26
05101520253035404550556065707580859095100105110115120125130135140145150f1 (ppm)
17.0
4
22.4
823
.78
31.3
732
.18
40.0
2
65.0
5
116.
4111
9.01
119.
7612
1.41
128.
92
132.
46
138.
16
140.
47
S18
NH8k
NH8k
1H and 13C spectra of compound 8k
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
4.24
2.12
8.04
2.06
2.02
0.88
0.99
1.00
1.00
1.01
1.42
1.46
1.49
1.53
1.56
1.58
1.61
1.62
1.64
1.67
1.69
1.71
1.73
1.77
1.79
2.13
2.14
2.14
2.16
2.38
2.40
2.40
2.42
4.42
6.60
6.62
6.69
6.70
6.71
6.72
6.73
6.73
6.98
6.98
7.00
7.00
7.01
7.02
7.08
7.08
7.10
7.10
05101520253035404550556065707580859095100105110115120125130135140145f1 (ppm)
21.1
822
.45
23.1
324
.87
25.2
825
.41
32.4
0
54.5
6
113.
58
117.
90
122.
1512
4.34
125.
2312
7.07
135.
92
142.
01
S19
NH8l
OH3C
NH8l
OH3C
1H and 13C spectra of compound 8l
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
14.5
3
1.95
1.97
3.08
0.91
1.01
1.00
1.01
1.43
1.49
1.52
1.61
1.64
1.70
1.75
1.78
2.12
2.13
2.36
2.37
3.79
4.40
6.17
6.18
6.26
6.27
6.28
6.29
6.99
7.01
7.29
0102030405060708090100110120130140150160f1 (ppm)
21.1
522
.48
23.2
024
.70
25.2
825
.40
32.4
9
54.6
855
.10
99.4
3
102.
88
118.
00
123.
1412
4.87
133.
16
143.
37
159.
17
S20
NH
CH3
CH3CH3
10a
NH
CH3
CH3CH3
10a
1H and 13C spectra of compound 10a
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
6.11
3.06
1.00
1.00
1.01
1.00
1.00
1.28
1.99
1.99
5.31
5.31
5.32
5.32
6.44
6.44
6.46
6.46
6.62
6.62
6.64
6.64
6.66
6.66
6.97
6.97
6.98
6.99
7.00
7.01
7.05
7.06
7.07
7.08
0102030405060708090100110120130140150f1 (ppm)
18.6
3
30.9
9
51.8
5
112.
99
117.
23
121.
5912
3.63
128.
3512
8.38
128.
56
143.
14
S21
NH
CH3
CH3CH3
10b
OH3C
NH
CH3
CH3CH3
10b
OH3C
1H and 13C spectra of compound 10b
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
6.00
2.98
3.01
1.00
1.01
1.00
1.00
1.27
1.96
3.75
5.20
6.05
6.05
6.06
6.20
6.21
6.22
6.23
6.97
6.99
0102030405060708090100110120130140150160170f1 (ppm)
18.6
9
31.0
9
51.9
6
55.0
9
98.6
4
102.
33
115.
38
124.
6812
6.02
128.
22
144.
69
160.
21
1H and 13C spectra of compound 10c
S22
NH10c
NH10c
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
6.24
3.02
3.05
0.99
1.00
1.00
1.00
1.17
1.23
1.25
1.31
1.54
HD
O
2.01
2.01
2.27
3.69
5.29
5.30
6.33
6.33
6.49
6.50
6.51
6.52
6.99
7.01
7.28
CD
Cl3
102030405060708090100110120130140150160f1 (ppm)
18.6
8
21.4
5
31.0
4
51.8
6
113.
68
118.
1011
9.18
123.
60
127.
4612
8.53
138.
32
143.
23
S23
NH10d
Cl
NH10d
Cl
1H and 13C spectra of compound 10d
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
6.02
3.09
0.81
1.01
1.00
1.02
1.02
1.20
1.21
1.23
1.30
1.43
1.98
HDO
1.98
3.52
3.92
5.32
5.32
5.33
6.45
6.46
6.59
6.60
6.61
6.62
6.96
6.98
7.29
CDC
l3
0102030405060708090100110120130140150160f1 (ppm)
18.5
7
31.1
0
52.1
5
112.
47
116.
95
120.
06
124.
6712
7.84
128.
44
133.
54
144.
22
1H and 13C spectra of compound 10e
S24
NH10e
NH10e
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
3.17
3.10
3.03
2.15
2.07
0.97
0.97
1.00
1.01
1.00
0.93
0.95
0.97
1.18
1.20
1.22
1.24
1.27
1.48
1.49
1.51
1.53
1.55
1.57
1.58
1.59
HD
O1.
601.
622.
412.
422.
442.
442.
462.
47
3.63
5.24
5.24
5.25
5.32
6.46
6.47
6.48
6.49
6.62
6.62
6.64
6.64
6.65
6.66
6.98
6.98
7.00
7.00
7.02
7.02
7.12
7.12
7.14
7.14
7.28
CD
Cl3
0102030405060708090100110120130140150f1 (ppm)
8.5
9
12.9
4
24.6
2
29.4
5
36.5
1
54.6
1
112.8
3
116.7
0
120.6
0123.2
2125.1
1128.2
0
134.8
0
143.9
6
1H and 13C spectra of compound 10f
S25
NH CH3
10f
OH3C
CH3
CH3
NH CH3
10f
OH3C
CH3
CH3
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
3.13
3.18
3.03
2.13
2.13
3.12
1.03
1.01
0.99
1.00
0.89
0.91
0.93
1.13
1.15
1.17
1.22
1.47
1.48
1.50
1.52
1.54
2.34
2.36
2.38
2.39
3.75
5.09
6.03
6.04
6.16
6.17
6.18
6.19
6.99
7.01
0102030405060708090100110120130140150160170f1 (ppm)
8.60
12.9
7
24.6
8
29.5
8
36.6
2
54.7
755
.06
98.4
2
101.
84
114.
38
122.
6212
4.22
134.
51
145.
37
160.
05
S26
NH10g
NH10g
1H and 13C spectra of compound 10g
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
3.42
3.29
3.05
2.19
3.19
2.19
0.99
0.95
1.01
1.00
0.92
0.94
0.95
1.12
1.16
1.18
1.20
1.25
1.28
1.29
1.30
1.31
1.46
1.48
1.50
1.52
1.52
1.53
1.54
1.55
1.56
1.57
1.58
1.59
1.67
1.80
1.82
2.00
2.02
2.08
2.09
2.24
HD
O2.
272.
382.
402.
422.
43
3.87
5.18
6.33
6.45
6.47
7.00
7.02
7.28
CD
Cl3
0102030405060708090100110120130140150160f1 (ppm)
8.61
13.0
0
21.3
7
24.6
7
29.4
7
36.5
0
54.6
1
113.
46
117.
5611
8.12
123.
1612
4.13
134.
75
138.
11
143.
94
