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TRANSCRIPT
S1
TEMPO-Mediated Aza-Diels–Alder Reaction: Synthesis of
Tetrahydropyridazines Using Ketohydrazones and Olefins
Xiu-Long Yang, Xie-Xue Peng, Fei Chen, and Bing Han*
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical
Engineering, Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of China
Supporting Information
• Contents page
• General S2
• General experimental procedure S2
• References S5
• Analytical data for products S5
• ORTEP plot for compound 3y S17
• Copies of 1H and 13C spectra S18
S2
General:
All reagents were purchased from commercial suppliers and used without further
purification. Flash chromatography was carried out with silica gel (200-300 mesh).
Analytical TLC was performed with silica gel GF254 plates, and the products were
visualized by UV detection. 1H NMR and 13C NMR (400 MHz, and 100.6 MHz respectively)
spectra were recorded in CDCl3 and DMSO–d6. Chemical shifts (δ) are reported in ppm
using TMS as internal standard and spin-spin coupling constants (J) are given in Hz. EI-MS
spectra were measured on a TRACE DSQ spectrometer by direct inlet at 70 eV. The high
resolution mass spectra (HRMS) were measured on a Bruker Daltonics APEX II 47e
spectrometer by ESI. Data collections for crystal structure were performed at room
temperature (293 K) using MoKα radiation on a Bruker APEXII diffractometer. Integration
of the frames and data reduction was carried out using SAINT. The structure was solved
by direct methods using SHELXS-97.
General experimental procedure:
Table S1. Involved hydrazones
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
S3
Table S2. Involved olefins
2a
2b
2c
2d
2e
2f
2g
2h
(CAS:5888-33-5)
2i
2j
2k
2l
2m
2n
2o
2p
2q
General procedure for the synthesis of ketohydrazones
Method A: for the synthesis of aromatic and aliphatic hydrazones 1a–1h and 1j–1q1, 2
The acetic acid (0.2 equiv) was added to a mixture of hydrazines (1.05 equiv) and
ketones (1.0 equiv) in anhydrous ethanol, and then heated at reflux for 2–4 hours under
Ar until the condensation was completed (monitored by TLC). The mixture was cooled in
ice and the precipitate was filtered off and rinsed with cooled ethanol and petroleum
ether.
Hydrazones 1h and 1o–q were used for next step after removing ethanol under vacuo
without further purification.
Notes: Due to the autoxidation of some hydrazones, the fresh prepared hydrazones were
used immediately.1c
Method B: for the synthesis of benzoyl hydrazone 1i3
S4
Benzoylhydrazine (408 mg, 3 mmol, 1.5 equiv) was added to a stirred solution of
acetophenone (240 mg, 2 mmol, 1 equiv) and glacial acetic acid (24 mg, 0.4 mmol, 0.2
equiv) in a mixed solvent of methanol/hexanes (1:5, 5 mL). The resulting suspension was
heated to reflux until the ketone was consumed completely. The solvent was evaporated
and purification of the crude product by flash column chromatography afforded
hydrazone 1i (381 mg, 80%) as a white solid.
General procedure for Aza-Diels–Alder reaction of hydrazones and alkenes
A mixture of ketohydrazones (0.5 mmol), alkenes (5.0 mmol) and TEMPO (1.5 mmol)
was placed in a 10 mL oven-dried Schlenk tube in toluene (1 mL) and stirred at 80 oC
under argon for 48–72 h. When hydrazones were consumed completely as monitored
by TLC, the mixture was diluted with EtOAc. The solvent was then removed under vacuo.
The residue was purified with chromatography column on silica gel (gradient eluent of
EtOAc/petroleum ethers: 1/20 to 1/5) to give the corresponding products 3 in yields
listed in Scheme 2 and Scheme 3. The identity and purity of the product was confirmed
by 1H and 13C NMR spectroscopic analysis.
General procedure for the one-pot Aza-Diels–Alder reaction of phenylhydrazines,
ketones and alkenes
The mixture of ketone (1 mmol), phenylhydrazine (1.05 mmol) and acetic acid (0.2 mmol)
S5
were refluxed in EtOH (2.0 mL) under argon until the condensation was completed
(monitored by TLC, about 3 h). After removing the solvent, TEMPO (3.0 mmol) and
alkenes (10.0 mmol) were added, and the mixture was stirred at 80 oC under argon for
48–72 h. When hydrazones were consumed completely as monitored by TLC, the
mixture was diluted with EtOAc. The solvent was then removed under vacuo. The
residue was purified with chromatography column on silica gel (gradient eluent of
EtOAc/petroleum ethers: 1/20 to 1/5) to give the corresponding products 3 in yields
listed in Scheme 4. The identity and purity of the product was confirmed by 1H and 13C
NMR spectroscopic analysis.
References:
(1) (a) Zhang, G.-W.; Miao, J.-M.; Zhao, Y.; Ge, H.-B. Angew. Chem., Int. Ed. 2012, 51,
8318–8321. (b) Hu, J.-T.; Xu, H.-C.; Nie, P.-J.; Xie, X.-B.; Nie, Z.-X.; Rao, Y. Chem. – Eur.
J. 2014, 20, 3932–3938. (c) Harej, M.; Dolenc, D. J. Org. Chem. 2007, 72, 7214–7221.
(2) Klein, J. J.; Hecht, S. Org. Lett. 2012, 14, 330−333.
(3) (a) Wu, P.-L.; Peng, S.-Y.; Magrath, J. Synthesis 1995, 435−438. (b) Berger, R.; Duff, K.;
Leighton, J. L. J. Am. Chem. Soc. 2004, 126, 5686−5687.
Analytical data for products:
methyl 2,6-diphenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3a)
White solid; (119 mg, 81%); mp: 99–100 oC; 1H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 7.6
Hz, 2H), 7.24–7.39 (m, 7H), 6.92 (m, 1H), 4.77 (d, J = 4.4 Hz, 1H), 3.70 (s, 3H), 2.75 (dd, J
= 17.2, 4.8 Hz, 1H), 2.55 (m, 1H), 2.45 (m, 1H), 2.16 (m, 1H); 13C NMR (100.6 MHz, CDCl3):
δ 172.0, 146.8, 139.3, 138.3, 129.0, 128.2, 127.8, 124.7, 120.3, 113.5, 54.0, 52.6, 20.8,
18.7; MS m/z (relative intensity, %): 294 (28.9), 249 (12.4), 235 (100), 143 (13.7), 104
(7.0), 77 (21.3); ESI-HRMS: m/z Calcd for C18H18N2O2+H+: 295.1441, found 295.1434.
methyl 6-phenyl-2-(p-tolyl)-2,3,4,5-tetrahydropyridazine-3-carboxylate (3b)
S6
White solid; (128 mg, 83%); mp: 139–140 oC ; 1H NMR (400 MHz, CDCl3): δ 7.80 (d, J =
8.4 Hz, 2H), 7.37 (t, J = 8.0, 7.2 Hz, 2H), 7.28 (m, 1H), 7.20 (d, J = 8.4 Hz, 2H ), 7.11 (d, J =
8.4Hz, 2H ), 4.75 (d, J = 4.4 Hz, 1H), 3.70 (s, 3H), 2.74 (m, 1H), 2.55 (m, 1H), 2.44 (m, 1H),
2.30 (s, 3H), 2.16 (m, 1H); 13C NMR (100.6 MHz, CDCl3): δ 172.1, 144.7, 138.7, 138.5,
129.6, 128.2, 127.7, 124.6, 113.6, 54.1, 52.5, 20.8, 20.4, 18.6; MS m/z (relative
intensity, %): 308 (36.2), 250 (19.4), 249 (100), 143 (7.7), 91 (16.4), 77 (10.2); ESI-HRMS:
m/z Calcd for C19H20N2O2+H+: 309.1598, found 309.1588.
methyl 2-(4-methoxyphenyl)-6-phenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3c)
White solid; (105 mg, 65%); mp: 126–127 oC ; 1H NMR (400 MHz, CDCl3): δ 7.78 (d, J = 7.2
Hz, 2H), 7.35 (t, J = 7.6 Hz, 2H), 7.27 (m, 1H), 7.23 (m, 2H), 6.88 (d, J = 8.8 Hz, 2H), 4.70 (d,
J = 4.4 Hz, 1H), 3.77 (s, 3H), 3.69 (s, 3H), 2.70 (m, 1H), 2.53 (m, 1H), 2.43 (m, 1H), 2.18 (m,
1H); 13C NMR (100.6 MHz, CDCl3): δ 172.1, 154.0, 141.2, 138.44, 138.41, 128.2, 127.6,
124.5, 115.1, 114.4, 55.6, 54.5, 52.5, 20.8, 18.5; MS m/z (relative intensity, %): 325 (11.7),
324 (55.2), 265 (100), 122 (364), 92 (5.8), 77 (13.2); ESI-HRMS: m/z Calcd for
C19H20N2O3+H+: 325.1547, found 325.1541.
methyl 2-(4-chlorophenyl)-6-phenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3d)
S7
White solid; (96 mg, 58%); mp: 123–124 oC ; 1H NMR (400 MHz, CDCl3): δ 7.78 (d, J = 7.2
Hz, 2H), 7.38 (t, J = 7.2 Hz, J = 7.62 Hz, 2H), 7.21–7.32 (m, 5H), 4.72 (d, J = 3.6 Hz, 1H),
3.71 (s, 3H), 2.75 (m, 1H), 2.56 (m, 1H), 2.44 (m, 1H), 2.17 (m, 1H); 13C NMR (100.6 MHz,
CDCl3): δ 171.6, 145.5, 140.2, 138.1, 128.9, 128.3, 128.1, 125.2, 124.8, 114.7, 54.0, 52.6,
20.7, 18.6; MS m/z (relative intensity, %): 330 (14.1), 328 (44.8), 271 (31.4), 269 (18.1),
234 (15.6), 143 (19.1), 77 (11.4); ESI-HRMS: m/z Calcd for C18H17ClN2O2+H+: 329.1051,
found 329.1047.
methyl-6-phenyl-2-(4-(trifluoromethyl)phenyl)-2,3,4,5-tetrahydropyridazine-3-carboxyl
ate (3e)
White solid; (100 mg, 55%); mp: 118–120 oC ; 1H NMR (400 MHz, CDCl3): δ 7.80 (d, J =
7.6 Hz, 2H), 7.53 (d. J = 8.8 Hz, 2H), 7.30–7.40 (m, 5H), 4.78 (d, J = 3.6 Hz, 1H), 3.71 (s,
3H), 2.76 (dd, J = 17.6, 4.4 Hz, 1H), 2.58 (m, 1H), 2.45 (m, 1H), 2.16 (m, 1H); 13C NMR
(100.6 MHz, CDCl3): δ 171.3, 149.1, 141.5, 137.8, 128.4, 128.3, 126.31 (q, 3JC,F = 3.6 Hz),
126.31, 124.9, 124.72 (q, 1JC,F = 269.1Hz), 121.70 (q, 2JC,F = 32.4Hz), 112.8, 53.7, 52.7, 20.6,
18.7; MS m/z (relative intensity, %): 363 (8.8), 362 (44.4), 304 (17.8), 303 (100),
143(15.4), 77 (10.6); ESI-HRMS: m/z Calcd for C19H17F3N2O2+H+: 363.1315, found
363.1302.
methyl 2-(4-cyanophenyl)-6-phenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3f)
S8
Yellow solid; (80 mg, 50%); mp: 113–114 oC ; 1H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 7.2
Hz, 2H), 7.56 (d, J = 8.8 Hz, 2H), 7.32–7.42 (m, 5H), 4.80 (d, J = 4.0 Hz, 1H), 3.73 (s, 3H),
2.80 (dd, J = 17.6, 4.8 Hz, 1H), 2.62 (m, 1H), 2.47 (m, 1H), 2.18 (m, 1H); 13C NMR (100.6
MHz, CDCl3): δ 170.8, 149.6, 142.9, 137.5, 133.3, 128.7, 128.4, 125.0, 119.9, 113.2, 102.2,
53.6, 52.8, 20.5, 18.8; MS m/z (relative intensity, %): 320 (6.3), 319 (28.4), 260 (100), 143
(17.0), 102 (11.0), 77 (9.7); ESI-HRMS: m/z Calcd for C19H17N3O2+H+: 320.1394, found
320.1392.
methyl 6-phenyl-2-(o-tolyl)-2,3,4,5-tetrahydropyridazine-3-carboxylate (3g)
Yellow oil; (93 mg, 60%); 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.0 Hz, 1H), 7.29–7.34
(m, 3H), 7.23–7.26 (m, 1H), 7.18–7.21 (m, 2H), 7.04–7.08 (m, 1H), 4.46 (t, J = 3.2 Hz, 1H )
3.63 (s, 3H), 2.73 (m, 1H), 2.45–2.55 (m, 2H), 2.31–2.40 (m, 4H); 13C NMR (100.6 MHz,
CDCl3): δ 171.7, 147.2, 139.5, 138.4, 131.7, 131.2, 128.1, 127.5, 126.3, 124.8, 124.5,
124.3, 57.2, 52.1, 21.9, 18.9, 18.8; MS m/z (relative intensity, %): 309 (6.1), 308 (30.0),
249 (100), 143 (9.0), 91 (11.8), 77 (5.8); ESI-HRMS: m/z Calcd for C19H20N2O2+Na+:
331.1417, found 331.1404.
methyl 6-(4-methoxyphenyl)-2-phenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3j)
S9
Yellow solid; (138 mg, 85%); mp: 95–97 oC; 1H NMR (400 MHz, CDCl3): δ 7.75 (m, 2H),
7.25–7.33 (m, 4H), 6.88–6.92 (m, 3H), 4.76 (d, J = 4.4 Hz, 1H), 3.83 (s, 3H), 3.70 (s, 3H),
2.72 (dd, J = 17.2, 5.6 Hz, 1H), 2.55 (m, 1H), 2.42 (m, 1H), 2.17 (m, 1H); 13C NMR (100.6
MHz, CDCl3): δ 172.1, 159.5, 146.8, 139.3, 131.2, 129.0, 126.0, 120.0, 113.6, 113.3, 55.3,
53.8, 52.5, 20.8, 18.6; MS m/z (relative intensity, %): 325 (11.9), 324 (60.0), 265 (100),
173 (7.2), 122 (49.3), 77 (17.0); ESI-HRMS: m/z Calcd for C19H20N2O3+H+: 325.1547, found
325.1537.
methyl 6-(4-nitrophenyl)-2-phenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3k)
Yellow solid; (111 mg, 65%); mp: 147–149 oC; 1H NMR (400 MHz, CDCl3): δ 8.21 (d, J = 8.8
Hz, 2H), 7.92 (d, J = 8.8 Hz, 2H), 7.30–7.37 (m, 4H), 7.00 (t, J = 6.4 Hz, 1H), 4.83 (s, 1H),
3.74 (s, 3H), 2.76 (dd, J = 17.2, 4.0 Hz, 1H), 2.61 (m, 1H), 2.49 (m, 1H), 2.19 (m, 1H); 13C
NMR (100.6 MHz, CDCl3): δ 171.3, 146.8, 146.2, 144.3, 136.7, 129.2, 124.9, 123.7, 121.5,
114.2, 54.2, 52.8, 20.4, 18.6; MS m/z (relative intensity, %): 339 (28.4), 280 (100), 234
(30.8), 104 (6.7), 77 (17.2), 44 (20.0); ESI-HRMS: m/z Calcd for C18H17N3O4+H+: 340.1292,
found 340.1285.
methyl 6-(2-bromophenyl)-2-phenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3l)
Yellow oil; (131 mg, 70%); 1H NMR (400 MHz, CDCl3): δ 7.60 (d, J = 1.2 Hz, 1H), 7.58 (d, J
S10
= 1.2 Hz, 1H), 7.43 (m, 1H), 7.17–7.35 (m, 6H), 6.90 (m, 1H), 4.77 (dd, J = 5.2, 2.0 Hz, 1H),
3.77 (s, 3H), 2.58–2.62 (m, 2H), 2.50 (m, 1H), 2.24 (m, 1H); 13C NMR (100.6 MHz, CDCl3):
δ 172.2, 146.6, 142.3, 140.8, 133.2, 130.7, 129.2, 129.0, 127.3, 121.7, 120.4, 113.6, 54.3,
52.6, 22.5, 20.8; MS m/z (relative intensity, %): 374 (34.9), 372 (36.6), 315 (97.4), 313
(100), 233 (25.1), 104 (16.4), 77 (38.4); ESI-HRMS: m/z Calcd for C18H17BrN2O2+H+:
373.0546, found 373.0539.
methyl 6-([1,1'-biphenyl]-4-yl)-2-phenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate
(3m)
White solid; (93 mg, 50%); mp: 201–203 oC; 1H NMR (400 MHz, CDCl3): δ 7.89 (d, J = 8.8
Hz, 2H), 7.62–7.64 (m, 4H), 7.45 (t, J = 7.6 Hz, 2H), 7.32–7.37 (m, 5H), 6.95 (m, 1H), 4.80
(d, J = 4.4 Hz, 1H ) 3.72 (s, 3H), 2.80 (dd, J = 17.2, 5.2 Hz, 1H), 2.59 (dd, J = 13.6, 6.8 Hz,
1H), 2.48 (m, 1H), 2.22 (m, 1H); 13C NMR (100.6 MHz, CDCl3): δ 172.2, 146.6, 142.3,
140.8, 133.2, 130.7, 129.2, 129.0, 127.3, 121.7, 120.4, 113.6, 54.3, 52.6, 22.5, 20.8; MS
m/z (relative intensity, %): 371 (12.0), 370 (58.4), 311 (100), 219 (8.1), 168 (36.8), 85
(37.4), 57 (47.2); ESI-HRMS: m/z Calcd for C24H22N2O2+H+: 371.1754, found 371.1743.
methyl 2-phenyl-6-(thiophen-2-yl)-2,3,4,5-tetrahydropyridazine-3-carboxylate (3n)
Brown solid; (105 mg, 70%); mp: 128–130 oC; 1H NMR (400 MHz, CDCl3): δ 7.29–7.33(m,
2H), 7.21–7.24 (m, 3H), 7.09 (d, J = 3.2 Hz, 1H), 6.98 (dd, J = 5.2, 4.0 Hz, 1H), 6.91 (t, J
=7.2 Hz, 1H), 4.77 (d, J = 4.8 Hz, 1H ) 3.71 (s, 3H), 2.70–2.75 (m, 1H), 2.41–2.55 (m, 2H),
2.13–2.22 (m, 1H); 13C NMR (100.6 MHz, CDCl3): δ 171.8, 146.3, 144.5, 136.7, 129.1,
126.9, 125.5, 122.9, 120.4, 113.4, 54.1, 52.6, 20.6, 19.3; MS m/z (relative intensity, %):
301 (9.1), 300 (50.2), 241 (100), 208 (4.9), 144 (14.1), 98 (14.7), 77 (15.6); ESI-HRMS: m/z
S11
Calcd for C16H16N2O2S+H+: 301.1005, found 301.1001.
methyl 6-methyl-2-phenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3o)
Yellow solid; (48 mg, 41%); mp: 107–109 oC; 1H NMR (400 MHz, CDCl3): δ 7.25 (t, J = 8.0
Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.84 (t, J = 7.2 Hz, 1H), 4.64 (s, 1H), 3.70 (s, 3H), 2.38 (m,
1H), 2.11 (m, 3H), 2.01 (s, 3H); 13C NMR (100.6 MHz, CDCl3): δ 172.3, 147.0, 142.3, 129.0,
119.4, 112.9, 53.3, 52.4, 24.2, 22.5, 20.9; MS m/z (relative intensity, %): 232 (29.5), 173
(100), 158 (12.4), 104 (9.6), 77 (22.1); ESI-HRMS: m/z Calcd for C13H16N2O2+H+: 233.1285,
found 233.1281.
methyl 6-(tert-butyl)-2-phenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3p)
Colorless oil; (75.5 mg, 55%); 1H NMR (400 MHz, CDCl3): δ 7.24 (dd, J = 8.8, 1.2 Hz, 2H),
7.15 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 4.61 (d, J = 3.2 Hz, 1H), 3.69 (s, 3H),
2.28–2.39 (m, 2H), 1.95–2.07 (m, 2H), 1.82 (s, 9H); 13C NMR (100.6 MHz, CDCl3): δ 172.5,
150.4, 147.1, 128.9, 119.1, 112.5, 53.6, 52.3, 38.2, 27.8, 21.1, 16.8; MS m/z (relative
intensity, %): 274 (32.4), 215 (100), 159 (26.8), 77 (11.4), 57 (24.3); ESI-HRMS: m/z Calcd
for C16H22N2O2+H+: 275.1754, found 275.1760.
ethyl 2,6-diphenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3r)
Yellow oil; (128 mg, 83%); 1H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 7.6 Hz, 2H), 7.36 (m,
2H), 7.24–7.31 (m, 5H), 6.92 (m, 1H), 4.75 (d, J = 4.8 Hz, 1H), 4.18 (q, J = 7.2 Hz, 2H), 2.75
S12
(dd, J = 16.8, 4.8 Hz, 1H), 2.55 (m, 1H), 2.46 (m, 1H), 2.17 (m, 1H), 1.19 (t, J = 7.2 Hz, 3H);
13C NMR (100.6 MHz, CDCl3): δ 171.4, 146.8, 139.2, 138.4, 129.0, 128.2, 127.8, 124.6,
120.2, 113.6, 61.4, 54.1, 20.7, 18.6, 14.2; MS m/z (relative intensity, %): 308 (33.7), 249
(24.8), 235 (100), 143 (13.6), 104 (8.0), 77 (23.4); ESI-HRMS: m/z Calcd for
C19H20N2O2+H+: 309.1598, found 309.1586.
butyl 2,6-diphenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3s)
Yellow oil; (146 mg, 88%); 1H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 8.0 Hz, 2H), 7.36 (t, J =
7.6 Hz, 2H), 7.25–7.31 (m, 5H), 6.92 (m, 1H), 4.77 (d, J = 4.4 Hz, 1H), 4.12 (t, J = 6.8 Hz,
2H), 2.75 (dd, J = 16.8, 4.8 Hz, 1H), 2.56 (m, 1H), 2.46 (m, 1H), 2.19 (m, 1H), 1.53 (m, 2H),
1.24 (m, 2H), 0.82 (t, J = 7.6 Hz, 3H); 13C NMR (100.6 MHz, CDCl3): δ 171.4, 146.7, 139.1,
138.3, 128.8, 128.0, 127.6, 124.5, 120.0, 113.5, 65.1, 54.0, 30.3, 20.7, 18.7, 18.6, 13.3;
MS m/z (relative intensity, %): 336 (18.0), 280 (17.7), 236 (16.5), 235 (100), 143 (8.0), 77
(13.2); ESI-HRMS: m/z Calcd for C21H24N2O2+H+: 337.1911, found 337.1901.
tert-butyl 2,6-diphenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3t)
Yellow oil; (143 mg, 85%); 1H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 7.6 Hz, 2H), 7.36 (m,
2H), 7.23–7.30 (m, 5H), 6.91 (m, 1H), 4.63 (d, J = 4.4 Hz, 1H), 2.74 (m, 1H), 2.51(m, 1H),
2.45 (m, 1H), 2.14 (m, 1H), 1.38 (s, 9H); 13C NMR (100.6 MHz, CDCl3): δ 170.4, 147.0,
139.1, 138.6, 128.9, 128.2, 127.6, 124.7, 120.0, 113.6, 82.0, 54.7, 27.9, 20.8, 18.6; MS
m/z (relative intensity, %): 336 (20.5), 280 (24.8), 236 (16.4), 235 (100), 143 (8.3), 77
(13.6); ESI-HRMS: m/z Calcd for C21H24N2O2+H+: 337.1911, found 373.1903.
benzyl 2,6-diphenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3u)
S13
Pale yellow solid; (141 mg, 76%); mp: 109–111 oC; 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J
= 7.2 Hz, 2H), 7.19–7.37 (m, 12H), 6.91 (s, 1H), 5.12 (m, 2H), 4.78 (d, J = 2.0 Hz, 1H), 2.64
(dd, J = 17.2, 4.8 Hz, 1H), 2.50 (m, 1H), 2.31 (m, 1H), 2.12 (m, 1H); 13C NMR (100.6 MHz,
CDCl3): δ 171.1, 146.8, 139.5, 138.3, 135.4, 129.0, 128.4, 128.14, 128.06, 127.9, 127.7,
124.6, 120.2, 113.7, 66.9, 54.0, 20.8, 18.6; MS m/z (relative intensity, %): 370 (25.4), 294
(5.3), 249 (16.1), 235 (100), 179 (11.8), 143 (12.5), 107 (14.7), 77 (25.9); ESI-HRMS: m/z
Calcd for C24H22N2O2+H+: 371.1754, found 371.1749.
phenyl 2,6-diphenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3v)
Pale yellow solid; (121 mg, 68%); mp: 110–112 oC; 1H NMR (400 MHz, CDCl3): δ 7.75 (d, J
= 7.6 Hz, 2H), 7.21–7.34 (m, 9H), 7.13 (m, 1H), 6.86–6.92 (m, 3H), 4.91 (d, J = 4.0 Hz, 1H),
2.77 (dd, J = 17.2, 5.2 Hz, 1H), 2.64 (m, 1H), 2.53 (m, 1H), 2.24 (m, 1H); 13C NMR (100.6
MHz, CDCl3): δ 170.0, 150.4, 146.8, 139.6, 138.3, 129.4, 129.1, 128.3, 128.0, 126.1, 124.8,
121.2, 120.6, 113.8, 54.2, 21.0, 18.7; MS m/z (relative intensity, %): 357 (7.9), 356 (32.2),
303 (8.7), 236 (16.3), 235 (100), 143 (12.3), 77 (17.4); ESI-HRMS: m/z Calcd for
C23H20N2O2+H+: 357.1598, found 357.1590.
N,2,6-triphenyl-2,3,4,5-tetrahydropyridazine-3-carboxamide (3w)
White solid; (98 mg, 55%); mp: 215–216 oC; 1H NMR (400 MHz, DMSO–d6): δ 10.34 (brs,
NH, 1H), 7.81 (d, J = 7.6 Hz, 2H), 7.59 (d, J = 8.0 Hz, 2H), 7.41 (t, J = 7.6 Hz, 2H), 7.29–7.33
(m, 7H), 7.06 (t, J = 7.2, 7.2 Hz, 1H), 6.85 (t, J = 6.0 Hz, 1H), 4.92 (d, J = 4.0 Hz, 1H), 2.76
(dd, J = 17.6, 5.2 Hz, 1H), 2.37–2.50 (m, 2H), 2.23 (m, 1H); 13C NMR (100.6 MHz,
S14
DMSO–d6): δ 169.4, 146.7, 138.9, 138.7, 138.3, 128.9, 128.7, 128.2, 127.5, 124.3, 123.5,
119.4, 119.3, 112.8, 54.5, 21.1, 18.0; MS m/z (relative intensity, %): 356 (3.5), 355 (11.5),
235 (100), 143 (9.8), 104 (5.2), 77 (12.3); ESI-HRMS: m/z Calcd for C23H21N3O+H+:
356.1757, found 356.1754.
(1S*,2S*,4S*)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl-2,6-diphenyl-2,3,4,5-tetrahydro
pyridazine-3-carboxylate (3x)
(dr = 62:38)
Colorless oil; (156 mg, 75%); 1H NMR (400 MHz, CDCl3): δ 7.77–7.81 (m, 5.4H), 7.27–7.39
(m, 18.9H), 6.88–6.92 (m, 2.7H), 4.76–4.77 (m, 2.7H), 4.61–4.66 (m, 2.7H), 2.73–2.78 (m,
2.7H), 2.55–2.62 (m, 2.7H), 2.36–2.47 (m, 2.7H), 2.14–2.22 (m, 2.7H), 1.68–1.78 (m,
2.7H), 1.55–1.62 (m, 5.4H), 1.43–1.48 (m, 2.7H), 0.94–1.07 (m, 6.4H), 0.82–0.84 (m,
2.7H), 0.67 (s, 5H), 0.66 (s, 3H), 0.64 (s, 3H), 0.62 (s, 5H), 0.51 (s, 3H), 0.48 (s, 5H); 13C
NMR (100.6 MHz, CDCl3): δ 171.4, 171.3, 146.74, 146.72, 139.02, 138.95, 138.5, 138.4,
128.91, 128.89, 128.17, 128.16, 127.7, 124.62, 124.60, 119.97, 119.95, 113.2, 113.1,
82.6, 82.4, 53.84, 53.78, 48.6, 48.3, 46.8, 44.80, 44.76, 39.0, 38.7, 33.53, 33.51, 26.8,
21.1, 20.8, 19.9, 19.8, 19.5, 19.2; MS m/z (relative intensity, %): 416 (13.9), 280 (32.2),
235 (100), 143 (7.8), 137 (4.9), 77 (8.8); ESI-HRMS: m/z Calcd for C27H32N2O2+H+:
417.2537, found 417.2545.
1,3,6-triphenyl-1,4,5,6-tetrahydropyridazine (3y)
Pale yellow solid; (86 mg, 55%); mp: 132–133 oC ; 1H NMR (400 MHz, CDCl3): δ 7.82 (d, J
= 7.6 Hz, 2H), 7.38 (t, J = 7.6 Hz, 2H), 7.21–7.30 (m, 8H), 7.17 (d, J = 7.2 Hz, 2H), 6.84 (t, J
= 6.8 Hz, 1H), 5.26 (s, 1H), 2.63 ( d, J = 13.2 Hz, 1H), 2.31 (m, 2H), 2.14 (m, 1H); 13C NMR
(100.6 MHz, CDCl3): δ 146.7, 140.9, 139.2, 138.8, 128.9, 128.8, 128.3, 127.5, 127.1, 126.0,
S15
124.5, 119.6, 113.7, 55.4, 25.0, 17.6; MS m/z (relative intensity, %): 313 (24.3), 312 (100),
235 (29.8), 103 (44.3), 92 (16.7), 77 (50.1); ESI-HRMS: m/z Calcd for C22H20N2+H+:
313.1699, found 313.1690.
1,3-diphenyl-6-(p-tolyl)-1,4,5,6-tetrahydropyridazine (3z)
Pale oil; (73 mg, 45%); 1H NMR (400 MHz, CDCl3): 7.83 (d, J = 8.0 Hz, 2H), 7.38 (t, J = 7.6
Hz, 2H), 7.21–7.31 (m, 5H), 7.04–7.10 (m, 4H), 6.84 (t, J = 7.2 Hz, 1H), 5.23 (s, 1H), 2.61
(d, J = 16.8 Hz, 1H), 2.27–2.32 (m, 5H), 2.15 (m, 1H); 13C NMR (100.6 MHz, CDCl3): δ
146.7, 139.1, 138.8, 137.9, 136.7, 129.4, 128.9, 128.3, 127.5, 125.9, 124.5, 119.6, 113.6,
55.2, 25.1, 21.0, 17.6; MS m/z (relative intensity, %): 326 (100), 233 (29.7), 207 (21.6),
156 (22.7), 103 (25.2), 77 (30.0); ESI-HRMS: m/z Calcd for C23H22N2+H+: 327.1856, found
327.1849.
6-(4-nitrophenyl)-1,3-diphenyl-1,4,5,6-tetrahydropyridazine (3aa)
Yellow solid; (84 mg, 47%); mp: 138–139 oC; 1H NMR (400 MHz, CDCl3): δ 8.16 (d, J = 8.4
Hz, 2H), 7.82 (d, J = 7.6 Hz, 2H), 7.30–7.42 (m, 5H), 7.24–7.25 (m, 4H), 6.88 (s, 1H), 5.36
(s, 1H), 2.69 (d, J = 18.0 Hz, 1H), 2.36–2.44 (m, 2H), 2.07 (m, 1H); 13C NMR (100.6 MHz,
CDCl3): δ 148.6, 147.2, 146.2, 139.6, 138.2, 129.1, 128.4, 128.0, 127.1, 124.5, 124.2,
120.2, 113.6, 55.0, 24.7, 17.5; MS m/z (relative intensity, %): 357 (100), 280 (6.0), 235
(24.5), 207 (14.7), 105 (12.6), 77 (39.9); ESI-HRMS: m/z Calcd for C22H19N3O2+H+:
358.1550, found 358.1545.
1,3-diphenyl-6-(pyridin-2-yl)-1,4,5,6-tetrahydropyridazine (3ab)
S16
Yellow solid; (78 mg, 50%); mp: 129–130 oC; 1H NMR (400 MHz, CDCl3): δ 8.65 (d, J = 4.0
Hz, 1H), 7.82 (d, J = 7.2 Hz, 2H), 7.48 (td, J = 8.0, 1.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 2H),
7.22–7.32 (m, 5H), 7.13 (dd, J = 6.8, 4.8 Hz, 1H), 7.00 (d, J = 8.0 Hz, 1H), 6.88 (t, J = 7.2 Hz,
1H), 5.35 (d, J = 3.6 Hz, 1H), 2.32–2.72 (m, 2H), 2.28 (m, 1H), 2.04 (m, 1H); 13C NMR
(100.6 MHz, CDCl3): δ 159.7, 150.0, 146.6, 139.6, 138.5, 136.7, 128.9, 128.2, 127.6,
124.5, 122.0, 121.0, 119.8, 113.5, 57.0, 22.8, 17.9; MS m/z (relative intensity, %): 313
(100), 312 (25.3), 235 (27.4), 215 (19.1), 207 (11.6), 103 (25.0), 77 (38.7); ESI-HRMS: m/z
Calcd for C21H19N3+H+: 314.1652, found 314.1656.
1,3-diphenyl-6-(pyridin-4-yl)-1,4,5,6-tetrahydropyridazine (3ac)
Pale yellow solid; (80 mg, 50%); mp: 127–128 oC; 1H NMR (400 MHz, CDCl3): δ 8.53 (d, J =
5.6 Hz, 2H), 7.81 (d, J = 7.2 Hz, 2H), 7.38 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.2 Hz, 1H),
7.24–7.25 (m, 4H), 7.11 (d, J = 6.0 Hz, 2H), 6.88 (m, 1H), 5.24 (s, 1H), 2.65 (m, 1H),
2.32–2.37 (m, 2H), 2.07 (m, 1H); 13C NMR (100.6 MHz, CDCl3): δ 150.3, 150.0, 146.4,
139.6, 138.7, 129.0, 128.3, 127.9, 124.6, 121.3, 120.2, 113.6, 54.6, 24.4, 17.6; MS m/z
(relative intensity, %): 313 (100), 312 (22.3), 235 (28.2), 207 (16.4), 103 (27.6), 77 (38.1);
ESI-HRMS: m/z Calcd for C21H19N3+H+: 314.1652, found 314.1646.
methyl 3-methyl-2,6-diphenyl-2,3,4,5-tetrahydropyridazine-3-carboxylate (3ae)
Pale yellow oil; (112 mg, 73%); 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J = 7.6 Hz, 2H), 7.34
(t, J = 7.6 Hz, 2H), 7.24–7.30 (m, 5H), 6.98 (t, J =6.8 Hz, 1H), 3.67 (s, 3H), 2.63 (m, 2H),
2.40 (m, 1H), 2.06 (m, 1H), 1.62 (s, 3H); 13C NMR (100.6 MHz, CDCl3): δ 175.0, 146.3,
S17
138.6, 138.3, 128.3, 128.2, 127.6, 124.5, 122.0, 119.7, 59.8. 52.6, 31.1, 21.6, 19.3; MS
m/z (relative intensity, %): 308 (13.5), 249 (100), 157 (9.6), 118 (6.7), 103 (7.8), 77 (18.5);
ESI-HRMS: m/z Calcd for C19H20N2O2+H+: 309.1598, found 309.1587.
6-methyl-1,3,6-triphenyl-1,4,5,6-tetrahydropyridazine (3af)
Yellow solid; (82 mg, 50%); mp: 133–135 oC; 1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 7.2
Hz, 2H), 7.39 (m, 6H), 7.30 (m, 2H), 7.23 (m, 4H), 6.98 (m, 1H), 2.65 (m, 1H), 2.29 (m, 1H),
2.18 (m, 2H), 1.90 (s, 3H); 13C NMR (100.6 MHz, CDCl3): δ 146.4, 145.3, 138.8, 138.1,
128.6, 128.2, 127.8, 127.1, 126.8, 125.8, 124.3, 121.3, 121.2, 59.7, 36.6, 26.3, 19.9; MS
m/z (relative intensity, %): 327 (23.5), 326 (100), 280 (7.6), 235 (42.6), 219 (16.5), 207
(16.5), 103 (43.7), 77 (54.2); ESI-HRMS: m/z Calcd for C23H22N2+H+: 327.1856, found
327.1844.
ORTEP Plot for Compound 3y:
Figure S-1. ORTEP of compound 3y, thermal ellipsoids are drawn at 30% probability
level.
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.122
2.135
2.154
2.167
2.181
2.200
2.214
2.394
2.411
2.427
2.439
2.454
2.470
2.486
2.533
2.549
2.565
2.581
2.717
2.730
2.761
2.773
3.702
4.767
4.778
6.905
6.914
6.919
6.926
6.933
7.235
7.271
7.288
7.303
7.316
7.340
7.353
7.372
7.390
7.799
7.818
0.99
1.01
1.00
1.00
2.94
1.00
1.03
7.02
2.06
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.66
20.75
52.56
53.98
76.68
77.00
77.32
113.52
120.27
124.66
127.83
128.24
129.04
138.34
139.31
146.76
172.02
S18
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.124
2.137
2.151
2.156
2.169
2.183
2.188
2.202
2.216
2.298
2.385
2.401
2.417
2.429
2.433
2.445
2.460
2.477
2.522
2.539
2.555
2.560
2.567
2.572
2.707
2.720
2.751
2.764
3.697
4.741
4.752
7.104
7.125
7.185
7.206
7.243
7.260
7.278
7.297
7.347
7.367
7.385
7.789
7.808
7.810
1.08
3.01
1.09
1.06
1.07
2.98
1.01
2.01
2.02
1.09
2.09
2.00
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.60
20.43
20.75
52.48
54.13
76.68
77.00
77.32
113.60
124.57
127.66
128.20
129.55
138.46
138.68
144.68
172.11
S19
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.120
2.133
2.152
2.166
2.180
2.198
2.212
2.373
2.389
2.405
2.417
2.433
2.448
2.465
2.503
2.519
2.535
2.552
2.685
2.698
2.728
2.741
3.688
3.774
4.698
4.709
6.870
6.892
7.210
7.232
7.243
7.265
7.283
7.335
7.354
7.373
7.771
7.789
0.98
1.02
1.00
1.00
2.78
2.97
0.93
1.89
1.99
0.99
1.92
1.89
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.50
20.78
52.46
54.52
55.59
76.68
77.00
77.32
114.41
115.07
124.47
127.56
128.18
138.41
138.44
141.20
153.97
172.08
S20
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.131
2.144
2.163
2.177
2.191
2.209
2.223
2.396
2.412
2.429
2.440
2.456
2.472
2.488
2.542
2.558
2.575
2.590
2.723
2.736
2.767
2.779
3.708
4.722
4.731
7.206
7.229
7.245
7.267
7.285
7.304
7.321
7.359
7.378
7.396
7.776
7.794
0.98
1.01
1.01
0.99
2.96
1.00
4.05
1.05
2.02
1.99
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.65
20.72
52.64
54.00
76.68
77.00
77.32
114.70
124.75
125.21
128.10
128.31
128.92
138.12
140.18
145.47
171.63
S21
11 10 9 8 7 6 5 4 3 2 1 0 ppm
−0.001
0.082
2.118
2.131
2.150
2.164
2.178
2.197
2.210
2.401
2.417
2.434
2.447
2.461
2.477
2.494
2.555
2.571
2.588
2.603
2.737
2.749
2.781
2.793
3.709
4.780
4.789
7.227
7.302
7.320
7.336
7.357
7.366
7.386
7.404
7.526
7.548
7.790
7.809
1.00
1.02
1.00
0.99
2.90
0.94
5.18
2.06
2.01
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.73
20.60
52.71
53.73
76.68
77.00
77.32
112.85
120.69
121.21
121.54
121.86
122.18
123.38
124.89
126.07
126.25
126.29
126.33
126.36
128.34
128.40
128.76
137.84
141.53
149.07
171.28
S22
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.137
2.150
2.169
2.183
2.197
2.216
2.229
2.425
2.441
2.458
2.470
2.485
2.501
2.517
2.587
2.603
2.621
2.636
2.775
2.787
2.819
2.831
3.731
4.793
4.803
7.253
7.322
7.345
7.364
7.383
7.402
7.419
7.553
7.575
7.790
7.808
1.00
1.01
1.00
1.01
3.03
1.01
5.01
2.09
2.00
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.79
20.52
52.82
53.58
76.68
77.00
77.32
102.20
113.22
119.86
125.00
128.38
128.72
133.33
137.52
142.88
149.55
170.83
S23
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.00
0
2.30
72.
318
2.33
12.
342
2.36
62.
384
2.39
22.
397
2.45
12.
467
2.49
42.
505
2.51
12.
520
2.52
82.
546
2.55
52.
699
2.71
52.
727
2.74
12.
753
2.76
83.
631
4.44
94.
458
4.46
6
7.04
37.
045
7.06
17.
080
7.08
27.
175
7.18
47.
192
7.20
37.
208
7.22
97.
245
7.26
57.
288
7.29
27.
303
7.31
07.
322
7.34
07.
716
7.73
47.
737
4.03
2.05
0.99
3.00
1.00
1.00
2.04
1.11
3.01
2.01
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.8
518
.90
21.8
9
52.0
757
.23
76.6
877
.00
77.3
2
124.
3112
4.48
124.
7912
6.33
127.
5312
8.13
131.
1613
1.68
138.
4513
9.49
147.
16
171.
69
S24
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.120
2.134
2.148
2.153
2.167
2.180
2.186
2.200
2.213
2.366
2.382
2.399
2.410
2.415
2.426
2.442
2.458
2.521
2.526
2.537
2.542
2.554
2.559
2.566
2.570
2.690
2.704
2.733
2.747
3.703
3.828
4.753
4.764
6.880
6.885
6.890
6.896
6.901
6.913
6.918
7.247
7.268
7.286
7.291
7.307
7.313
7.324
7.330
7.731
7.738
7.743
7.755
7.760
7.767
1.00
1.00
1.02
1.00
3.03
3.06
0.97
2.91
4.00
2.00
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.65
20.80
52.50
53.85
55.27
76.68
77.00
77.32
113.32
113.61
119.95
125.96
129.00
131.22
139.33
146.85
159.53
172.11
S25
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.164
2.178
2.183
2.196
2.210
2.229
2.433
2.449
2.477
2.486
2.493
2.509
2.525
2.583
2.600
2.617
2.632
2.729
2.740
2.773
2.783
3.744
4.830
6.981
6.997
7.013
7.253
7.299
7.319
7.328
7.335
7.353
7.369
7.904
7.926
8.197
8.219
1.01
1.02
1.01
1.00
3.03
1.00
1.00
4.02
2.00
2.00
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.55
20.44
52.77
54.23
76.68
77.00
77.32
114.15
121.49
123.66
124.86
129.20
136.74
144.28
146.18
146.78
171.32
S26
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.196
2.209
2.219
2.229
2.232
2.242
2.250
2.254
2.263
2.268
2.274
2.288
2.475
2.485
2.491
2.495
2.501
2.508
2.516
2.522
2.527
2.534
2.540
2.584
2.587
2.590
2.595
2.609
2.619
3.771
4.756
4.761
4.769
4.774
6.878
6.881
6.885
6.899
6.902
6.913
6.916
6.919
7.166
7.171
7.185
7.190
7.205
7.210
7.211
7.215
7.228
7.234
7.237
7.257
7.272
7.277
7.289
7.294
7.315
7.317
7.333
7.336
7.352
7.355
7.420
7.425
7.439
7.444
7.581
7.584
7.601
7.604
1.04
1.07
2.01
3.01
1.00
1.01
5.99
1.04
1.00
0.97
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
20.76
22.48
52.59
54.31
76.68
77.00
77.32
113.56
120.38
121.73
127.34
129.01
129.23
130.67
133.15
140.76
142.34
146.59
172.23
S27
11 10 9 8 7 6 5 4 3 2 1 0 ppm
-0.0
01
2.15
32.
172
2.18
52.
200
2.21
82.
231
2.42
02.
436
2.46
62.
479
2.49
52.
511
2.55
02.
565
2.58
22.
753
2.76
52.
797
2.80
73.
712
4.78
74.
794
6.93
37.
235
7.32
07.
328
7.35
87.
423
7.44
27.
460
7.61
17.
625
7.87
07.
890
1.01
1.04
1.00
1.01
3.00
1.00
1.00
5.01
2.04
4.06
2.01
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.68
20.77
52.59
54.05
76.68
77.00
77.31
113.59
120.36
125.07
126.92
127.29
128.77
129.07
137.33
139.01
140.46
140.70
146.75
172.01
S28
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.129
2.141
2.159
2.173
2.187
2.205
2.219
2.401
2.417
2.433
2.444
2.449
2.460
2.474
2.490
2.499
2.503
2.515
2.521
2.533
2.549
2.700
2.714
2.743
2.754
3.710
4.757
4.769
6.896
6.914
6.932
6.974
6.983
6.986
6.996
7.084
7.092
7.214
7.228
7.235
7.243
7.255
7.287
7.305
7.327
1.01
2.01
1.00
3.02
1.01
1.00
1.00
1.00
2.97
2.02
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
19.28
20.56
52.63
54.10
76.68
77.00
77.32
113.45
120.35
122.87
125.52
126.90
129.06
136.71
144.54
146.30
171.85
S29
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.007
2.057
2.075
2.089
2.113
2.151
2.163
2.348
2.358
2.363
2.370
2.377
2.382
2.394
3.699
4.643
6.821
6.839
6.857
7.131
7.151
7.234
7.252
7.274
3.20
3.07
1.01
3.01
1.00
1.01
1.98
2.27
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
20.93
22.54
24.16
52.36
53.30
76.68
77.00
77.32
112.90
119.44
128.96
142.34
146.98
172.28
S30
11 10 9 8 7 6 5 4 3 2 1 0 ppm
−0.000
0.077
1.182
1.949
1.959
1.970
1.982
1.990
1.999
2.002
2.021
2.033
2.054
2.066
2.285
2.290
2.325
2.329
2.339
2.347
2.354
2.358
2.364
2.371
2.377
2.382
2.388
3.688
4.610
4.618
6.805
6.822
6.840
7.140
7.160
7.226
7.229
7.248
7.251
7.269
9.01
2.01
1.97
3.00
1.00
1.01
2.00
2.01
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
16.75
21.10
27.81
38.15
52.26
53.63
76.68
77.00
77.32
112.49
119.09
128.88
147.14
150.38
172.48
S31
11 10 9 8 7 6 5 4 3 2 1 0 ppm
−0.001
1.176
1.194
1.211
2.128
2.141
2.155
2.160
2.173
2.187
2.206
2.220
2.407
2.423
2.440
2.451
2.455
2.467
2.482
2.498
2.530
2.546
2.563
2.579
2.720
2.734
2.764
2.776
4.155
4.173
4.191
4.208
4.743
4.755
6.893
6.902
6.905
6.914
6.925
6.935
6.946
7.242
7.269
7.287
7.303
7.313
7.337
7.341
7.353
7.372
7.391
7.796
7.815
3.15
1.01
1.05
1.02
0.99
1.99
1.00
1.10
5.01
2.17
1.99
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
14.16
18.63
20.74
54.11
61.45
76.68
77.00
77.32
113.60
120.21
124.64
127.75
128.21
128.96
138.42
139.22
146.84
171.37
S32
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.797
0.816
0.834
1.190
1.208
1.227
1.246
1.264
1.283
1.488
1.504
1.524
1.534
1.540
1.558
2.143
2.156
2.175
2.189
2.203
2.221
2.235
2.409
2.425
2.441
2.453
2.457
2.469
2.484
2.501
2.538
2.554
2.571
2.588
2.725
2.739
2.769
2.781
4.101
4.117
4.134
4.764
4.775
6.881
6.893
6.903
6.913
6.924
6.934
6.946
7.251
7.272
7.290
7.303
7.314
7.355
7.375
7.393
7.793
7.813
2.99
2.33
2.61
1.03
1.05
1.03
1.00
1.99
0.98
1.01
4.95
2.10
2.01
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
13.33
18.56
18.72
20.67
30.34
53.95
65.11
76.69
77.00
77.32
113.47
120.05
124.50
127.60
128.05
128.80
138.30
139.11
146.74
171.35
S33
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
1.383
1.464
2.102
2.107
2.112
2.121
2.125
2.139
2.153
2.167
2.171
2.185
2.404
2.420
2.436
2.448
2.452
2.464
2.490
2.502
2.508
2.514
2.519
2.524
2.535
2.710
2.728
2.754
2.766
4.628
4.639
6.880
6.891
6.901
6.910
6.914
6.922
6.934
7.232
7.260
7.279
7.284
7.301
7.311
7.335
7.346
7.366
7.385
7.791
7.810
9.04
1.00
1.00
1.17
1.00
1.00
1.06
4.97
2.14
2.09
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.65
20.81
27.89
54.73
76.68
77.00
77.32
82.01
113.64
120.05
124.68
127.65
128.19
128.89
138.60
139.07
147.05
170.40
S34
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.001
2.078
2.091
2.110
2.124
2.137
2.156
2.170
2.254
2.269
2.298
2.312
2.329
2.345
2.472
2.488
2.505
2.520
2.609
2.621
2.652
2.664
4.775
4.779
5.071
5.102
5.147
5.177
6.908
7.192
7.218
7.233
7.290
7.332
7.350
7.366
7.750
7.768
0.97
0.97
0.96
1.00
0.94
2.08
1.00
12.3
5
2.00
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.61
20.81
53.98
66.86
76.68
77.00
77.32
113.68
120.25
124.64
127.74
127.89
128.06
128.14
128.40
128.95
135.41
138.34
139.47
146.80
171.08
S35
11 10 9 8 7 6 5 4 3 2 1 0 ppm
−0.075
0.000
2.189
2.202
2.220
2.235
2.249
2.267
2.281
2.488
2.504
2.521
2.533
2.548
2.563
2.579
2.612
2.628
2.645
2.661
2.740
2.753
2.783
2.796
4.908
4.918
6.861
6.878
6.896
6.917
7.087
7.105
7.123
7.154
7.214
7.220
7.234
7.254
7.276
7.284
7.294
7.303
7.323
7.344
7.742
7.761
1.02
1.08
1.02
1.00
1.00
2.94
1.01
9.08
2.00
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.72
20.95
54.21
76.68
77.00
77.32
113.80
120.57
121.18
124.75
126.10
127.95
128.29
129.14
129.40
138.32
139.58
146.85
150.38
170.05
S36
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.207
2.220
2.233
2.251
2.265
2.368
2.383
2.413
2.426
2.456
2.497
2.755
2.768
2.799
4.914
4.924
6.833
6.848
6.862
7.043
7.061
7.079
7.294
7.309
7.326
7.389
7.408
7.427
7.584
7.604
7.802
7.821
10.340
1.03
2.48
0.98
1.00
1.03
1.07
7.14
2.10
2.00
2.00
0.99
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
18.00
21.11
38.87
39.08
39.29
39.50
39.71
39.92
40.13
54.36
112.84
119.28
119.44
123.49
124.34
127.52
128.24
128.69
128.93
138.28
138.69
138.86
146.69
169.40
S37
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
0.479
0.514
0.622
0.638
0.666
0.671
0.822
0.827
0.842
0.936
0.953
0.979
0.986
1.013
1.043
1.427
1.437
1.460
1.469
1.480
1.551
1.561
1.569
1.576
1.584
1.599
1.615
1.678
1.698
1.712
1.725
1.732
1.745
1.757
1.777
2.173
2.187
2.206
2.220
2.374
2.391
2.402
2.407
2.418
2.435
2.451
2.568
2.574
2.578
2.585
2.591
2.730
2.740
2.743
2.774
2.784
4.617
4.629
4.636
4.648
4.656
4.766
4.773
6.882
6.887
6.890
6.895
6.903
6.909
7.244
7.272
7.285
7.297
7.306
7.321
7.338
7.353
7.371
7.389
7.392
7.771
7.784
7.789
7.792
7.802
7.806
5.00
3.00
5.01
3.01
3.04
5.00
1.70
6.43
2.74
5.42
2.74
2.69
2.72
2.71
2.69
2.68
2.72
2.69
18.9
2
5.37
0.450.500.550.600.650.70 ppm
0.479
0.514
0.622
0.638
0.666
0.671
5.002
3.000
5.009
3.013
3.035
5.004
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
11.01
11.34
18.73
18.78
19.16
19.54
19.84
19.86
20.75
21.09
26.83
33.51
33.53
38.66
38.97
44.76
44.80
46.76
48.34
48.60
53.78
53.84
76.68
77.00
77.32
82.44
82.63
113.11
113.20
119.95
119.97
124.60
124.62
127.68
128.16
128.17
128.89
128.91
138.40
138.47
138.95
139.02
146.72
146.74
171.30
171.39
S38
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.090
2.114
2.133
2.138
2.157
2.181
2.288
2.298
2.307
2.313
2.322
2.330
2.602
2.646
5.262
6.825
6.843
6.860
7.164
7.182
7.214
7.224
7.237
7.253
7.269
7.287
7.301
7.305
7.359
7.378
7.397
7.818
7.837
1.02
1.99
1.00
1.01
1.00
2.05
8.15
2.01
2.04
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
17.58
25.03
55.43
76.68
77.00
77.32
113.66
119.65
124.52
126.01
127.12
127.53
128.27
128.78
128.88
138.77
139.21
140.91
146.73
S39
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.001
2.101
2.125
2.148
2.167
2.191
2.271
2.280
2.295
2.318
2.590
2.632
5.228
6.820
6.838
6.855
7.045
7.066
7.082
7.102
7.213
7.234
7.252
7.287
7.308
7.358
7.377
7.396
7.816
7.836
1.02
5.10
1.02
1.03
1.00
4.08
5.21
2.10
2.01
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
17.59
21.02
25.07
55.20
76.68
77.00
77.32
113.61
119.56
124.49
125.92
127.49
128.26
128.87
129.45
136.72
137.87
138.80
139.11
146.74
S40
11 10 9 8 7 6 5 4 3 2 1 0 ppm
−0.000
2.020
2.036
2.052
2.067
2.080
2.095
2.112
2.362
2.373
2.406
2.417
2.438
2.668
2.713
5.361
6.885
7.245
7.295
7.314
7.332
7.350
7.372
7.397
7.415
7.813
7.832
8.145
8.166
1.01
2.01
1.00
1.00
1.00
4.04
5.00
2.00
1.97
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
17.46
24.74
55.00
76.68
77.00
77.32
113.55
120.23
124.19
124.53
127.14
127.96
128.38
129.08
138.20
139.59
146.17
147.22
148.55
S41
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
0.081
1.990
2.006
2.023
2.034
2.039
2.050
2.067
2.083
2.230
2.242
2.255
2.263
2.276
2.289
2.296
2.309
2.321
2.624
2.636
2.668
2.680
2.697
2.702
2.707
2.713
2.718
5.345
5.354
6.841
6.859
6.876
6.991
7.011
7.121
7.134
7.139
7.151
7.223
7.227
7.249
7.267
7.280
7.296
7.316
7.353
7.372
7.391
7.458
7.462
7.478
7.481
7.497
7.501
7.814
7.832
8.641
8.651
1.01
1.02
2.00
1.00
0.99
1.00
1.00
5.05
2.01
1.02
2.00
1.00
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
17.89
22.79
56.99
76.68
77.00
77.32
113.47
119.75
121.01
122.05
124.47
127.60
128.20
128.90
136.66
138.54
139.62
146.55
150.01
159.73
S42
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.000
2.021
2.040
2.052
2.065
2.070
2.084
2.094
2.114
2.322
2.331
2.342
2.349
2.362
2.373
2.637
2.642
2.681
5.240
6.857
6.864
6.871
6.878
6.886
6.890
6.899
7.107
7.122
7.242
7.251
7.254
7.278
7.297
7.315
7.363
7.382
7.401
7.800
7.818
8.520
8.534
1.00
2.00
1.00
1.00
1.01
2.04
4.00
1.00
2.03
2.00
2.00
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
17.55
24.36
54.58
76.68
77.00
77.32
113.62
120.16
121.33
124.55
127.87
128.34
129.03
138.36
139.60
146.36
149.99
150.35
S43
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.001
1.619
2.031
2.048
2.065
2.081
2.098
2.364
2.381
2.397
2.414
2.430
2.561
2.577
2.605
2.621
2.632
2.649
2.677
2.693
3.674
6.967
6.984
7.001
7.235
7.255
7.261
7.279
7.300
7.324
7.343
7.362
7.747
7.766
3.00
1.00
1.00
2.01
2.93
0.97
4.90
2.09
1.96
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
19.34
21.59
31.13
52.55
59.84
76.68
77.00
77.32
119.67
121.99
124.46
127.57
128.18
128.33
138.32
138.65
146.28
174.95
S44
11 10 9 8 7 6 5 4 3 2 1 0 ppm
0.072
1.897
2.154
2.169
2.183
2.193
2.219
2.261
2.284
2.297
2.325
2.612
2.639
2.648
2.668
2.678
6.971
6.986
7.221
7.236
7.285
7.304
7.321
7.363
7.380
7.405
7.424
7.819
7.837
3.00
2.04
1.01
1.05
1.02
4.02
2.04
6.09
2.00
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
19.87
26.27
36.65
59.71
76.68
77.00
77.32
121.19
121.33
124.32
125.83
126.77
127.14
127.78
128.19
128.60
138.12
138.81
145.34
146.42
S45