Novel and Efficient Aerobic Oxidative Synthesis ... · State Key Laboratory of Applied Organic Chemistry, ... for the synthesis of aromatic and aliphatic ... Klein, J. J.; Hecht,

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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

[email protected]

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

mailto:[email protected]

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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

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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

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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)

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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)

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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)

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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)

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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)

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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),


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

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= 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

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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

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(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,


(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)

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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,


(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),


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,


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,


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,


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)


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


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)


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

Documents

Novel and Efficient Aerobic Oxidative Synthesis ... · State Key Laboratory of Applied Organic Chemistry, ... for the synthesis of aromatic and aliphatic ... Klein, J. J.; Hecht,