TBATB) as pre-catalyst

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33 Experimental:

Preparation of n-tetrabutylammonium tribromide (TBATB):

An amount of 0.05 g (0. 27 mmol) of vanadium pentoxide (V2O5), was added to 5 mL (44.12 mmol) of 30% hydrogen peroxide (H2O2) taken in a pre-cooled 250 mL beaker (care should be taken to maintain ice-cold condition as the reaction between V2O5 and H2O2 is exothermic). The reaction mixture was stirred at 0 – 5 °C temperature in an ice- water bath till all the V2O5 dissolved and the solution became reddish-brown. To it was added a solution of 5.67 g (47.65 mmol) potassium bromide (KBr) and 7.7 g (23.81 mmol) of tetrabutylammonium bromide (TBAB), dissolved in 25 mL of 1M H2SO4. An orange-yellow precipitate started to appear after 5 minutes of stirring. The mixture was stirred continuously for about 30 minutes subsequent upon which the whole was kept standing in an ice-bath for 1h, to give a bright orange colored compound. The isolated yield was 80%, M.p. 75 °C.

General procedure for the synthesis of highly and fully functionalized piperidines:

To a solution of amine (2 mmol) and methyl acetoacetate (1 mmol) in 5 mL of ethanol was added TBATB (0.1 mmol) and stirred at room temperature. After 20 min, aromatic aldehyde (2 mmol) was added into the above reaction mixture and stirring was further continued. After completion of the reaction, thick precipitate came out after stipulated reaction time. The solid product was filtered off and washed with ethanol, which was recrystallized from hot ethanol.

Methyl 2,6-bis(4-methylphenyl)-1-phenyl-4-(phenylamino)-1,2,5,6-tetrahydropyridine-3- carboxylate (122a)

White solid (0.381 g, 78%); M.p. 215-217 °C; IR (KBr): 1657, 1591 cm^-1. ¹H NMR (400 MHz, CDCl3): δ

= 2.32 (s, 3H), 2.33 (s, 3H), 2.75 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H), 2.86 (dd, J = 5.6, J = 15.2 Hz, 1H), 3.92 (s, 3H), 5.11 (d, J = 3.2 Hz, 1H), 6.30 (d, J = 8.0 Hz, 2H), 6.39 (s, 1H), 6.52 (d, J = 8.0 Hz, 2H), 6.59 (t, J = 7.2 Hz, 1H), 7.02-7.10 (m, 11H), 7.19 (d, J = 8.0 Hz, 2H), 10.25 (s, 1H); ¹³C NMR (100 MHz, CDCl3): δ = 21.2, 21.3, 33.8, 51.2, 55.0, 58.1, 98.2, 113.0, 116.1, 125.8, 126.0, 126.5, 126.7, 128.9, 129.0, 129.1, 129.4, 136.0, 136.8, 138.1, 139.8, 141.1, 147.2, 156.5,

Chapter II Experimental Section

34

168.8; Anal. Calcd for C33H32N2O2 (488.63): C, 81.12; H, 6.60; N, 5.73; found: C, 80.96, H, 6.55, N, 5.80.

Methyl 1,2,6-triphenyl-4-(phenylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate (122b) White solid (0.373 g, 81%); M.p. 185-186 °C; IR (KBr): 3444, 1661, 1591 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 2.75 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H, 5-Ha), 2.86 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 3.93 (s, 3H, OCH3), 5.14 (d, J = 4.4 Hz, 1H, 6- H), 6.27 (d, J = 8.0 Hz, 2H), 6.44 (s, 1H, 2-H), 6.51 (d, J = 8.8 Hz, 2H), 6.59 (t, J = 7.2 Hz, 1H), 7.03-7.10 (m, 5H), 7.16 (d, J = 8.0 Hz, 2H), 7.24-7.32 (m, 8H), 10.24 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 33.8 (C-5), 51.2, 55.2 (C-2), 58.3 (C-6), 98.0 (C-3), 113.0 (2C), 116.3, 125.9, 126.0 (2C), 126.5 (3C), 126.8 (2C), 127.3, 128.4 (2C), 128.8 (2C), 128.9 (2C), 129.0 (2C), 137.9, 142.9, 144.0, 147.1, 156.4 (C-4), 168.7 (C=O); Anal. Calcd for C31H28N2O2 (460.57): C, 80.84; H, 6.13; N, 6.08; found: C, 80.72; H, 6.07; N, 6.09.

Methyl 2,6-bis(4-methoxyphenyl)-1-phenyl-4-(phenylamino)-1,2,5,6-tetrahydropyridine- 3-carboxylate (122c)

White solid (0.344 g, 66%); M.p. 186-188 °C; IR (KBr): 1654, 1593 cm^-1; ¹H NMR (400 MHz, CDCl3):

δ 2.75 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H, 5-Ha), 2.85 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 3.78 (s, 3H, ArOCH3), 3.79 (s, 3H, ArOCH3), 3.92 (s, 3H, OCH3), 5.07 (d, J = 3.2 Hz, 1H, 6-H), 6.34-6.38 (m, 3H), 6.52 (d, J = 8.0 Hz, 2H), 6.60 (t, J = 7.2 Hz, 1H), 6.81 (d, J = 8.8 Hz, 4H), 7.05 (d, J = 8.4 Hz, 2H), 7.06 (d, J =8.8 Hz, 2H), 7.07 (t, J = 7.2 Hz, 1H), 7.11 (d, J = 7.2 Hz, 2H), 7.21 (d, J

= 8.8 Hz, 2H), 10.27 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 33.9 (C-5), 51.2, 54.7 (C-2), 55.4 (2C), 57.7 (C-6), 98.2 (C-3), 113.1 (2C), 113.7 (2C), 114.1 (2C), 116.2, 125.8, 125.9 (2C), 127.6 (2C), 127.8 (2C), 129.0 (4C), 134.8, 136.0, 138.1, 147.1, 156.5 (C-4), 158.2, 158.8, 168.8 (C=O); Anal. Calcd for C33H32N2O4 (520.63): C, 76.13; H, 6.20; N, 5.38; found C, 76.01; H, 6.11; N, 5.49.

Methyl 2,6-bis(4-chlorophenyl)-1-phenyl-4-(phenylamino)-1,2,5,6-tetrahydropyridine-3- carboxylate (122d)

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35

White solid (0.450 g, 85%); M.p. 225-227 °C; IR (KBr):

1660, 1591 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 2.74 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H, 5-Ha), 2.82 (dd, J = 5.6 Hz, J

= 15.2 Hz, 1H, 5-Hb), 3.92 (s, 3H, OCH3), 5.09 (d, J = 2.4 Hz, 1H, 6-H), 6.35 (s, 1H, 2-H), 6.40 (d, J = 8.0 Hz, 2H), 6.45 (d, J = 8.0 Hz, 2H), 6.64 (t, J = 7.2 Hz, 1H), 7.05 (d, J

= 8.0 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 7.10 (t, J = 7.6 Hz, 2H), 7.15 (d, J = 7.2 Hz, 2H), 7.24 (m, 5H), 10.25 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 33.8 (C-5), 51.3, 54.8 (C-2), 57.5 (C-6), 97.6 (C-3), 113.1 (2C), 116.9, 125.9 (2C), 126.2, 127.9 (2C), 128.2 (2C), 128.6 (2C), 128.9 (2C), 129.2 (4C), 132.3, 133.0, 137.7, 141.0, 142.5, 146.6, 156.2 (C-4), 168.4 (C=O); Anal. Calcd for C31H26N2O2Cl2 (529.46): C, 70.32; H, 4.95; N, 5.29; found: C, 70.29; H, 4.83; N, 5.34.

Methyl 2,6-bis(4-bromophenyl)-1-phenyl-4-(phenylamino)-1,2,5,6-tetrahydropyridine-3- carboxylate (122e)

Light yellow solid (0.476 g, 77%); M.p. 245-247 °C; IR (KBr): 1661, 1590 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 2.74 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H, 5-Ha), 2.82 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 3.93 (s, 3H, OCH3), 5.08 (d, J = 3.6 Hz, 1H, 6-H), 6.34 (s, 1H, 2-H), 6.40 (d, J = 7.6 Hz, 2H), 6.45 (d, J = 8.8 Hz, 2H), 6.65 (t, J = 7.2 Hz, 1H), 7.00 (d, J = 8.4 Hz, 2H), 7.08 (t, J = 7.2 Hz, 2H), 7.15 (t, J = 7.2 Hz, 1H), 7.16 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 10.24 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 33.8 (C-5), 51.3, 54.9 (C-2), 57.5 (C-6), 97.6 (C-3), 113.0 (2C), 116.9, 120.4, 121.1, 125.9 (2C), 126.2, 128.3 (2C), 128.6 (2C), 129.18 (2C), 129.2 (2C), 131.5 (2C), 131.9 (2C), 137.7, 141.6, 143.0, 146.5, 156.1 (C-4), 168.4 (C=O); Anal Calcd for C31H26N2O2Br2 (618.37): C, 60.21; H, 4.24; N, 4.53; found: C, 60.45; H, 4.15; N, 4.97.

Methyl 2,6-bis(3,4,5-trimethoxyphenyl)-1-phenyl-4- (phenylamino)-1,2,5,6-tetrahydropy

-ridine-3-carboxylate (122f)

Light yellow solid (0.418 g, 65%); M.p. 197-199 °C;

IR (KBr): 1655, 1594 cm^-1; ¹H NMR (400 MHz,

N NH

OMe O

OMe MeO

OMe

OMe MeO

OMe N

NH

OMe O

Cl Cl

Chapter II Experimental Section

36

CDCl3): δ 2.77 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H, 5-Ha), 2.95 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 3.70 (s, 6H, 2 x ArOCH3), 3.74 (s, 6H, 2 x ArOCH3), 3.84 (s, 3H, ArOCH3), 3.85 (s, 3H, ArOCH3), 3.90 (s, 3H, OCH3), 5.03 (d, J = 3.2 Hz, 1H, 6-H), 6.34(s, 1H, 2- H), 6.35 (s, 2H), 6.39 (d, J = 7.7 Hz, 2H), 6.53 (s, 2H), 6.57 (d, J = 8.0 Hz, 2H), 6.65 (t, J = 7.6 Hz, 1H), 7.09 (d, J = 8.0 Hz, 2H), 7.12 (t, J = 7.2 Hz, 1H), 7.15 (d, J = 7.6 Hz, 2H), 10.26 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 33.8 (C-5), 51.1, 55.6 (C-2), 56.0 (4C), 58.3 (C-6), 61.0 (2C), 97.3 (C-3), 103.2 (2C), 103.9 (2C), 113.1 (2C), 116.6, 126.2, 126.3 (2C), 128.9 (4C), 136.5, 137.0, 137.8, 138.5, 139.7, 147.0, 153.1 (2C), 153.4 (2C), 157.0 (C-4), 168.5 (C=O); Anal. Calcd for C37H40N2O8 (640.73): C, 69.36;

H, 6.29; N, 4.37.; found C, 69.28; H, 6.24; N, 4.46.

Methyl 2,6-bis(3-nitrophenyl)-1-phenyl-4-(phenylamino)-1,2,5,6-tetrahydropyridine-3- carboxylate (122g)

Yellow solid (0.198 g, 36%); M.p. 182-183 ^oC. IR (KBr): 3436 (NH), 1655, 1595 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 2.88 (d, J = 4.0 Hz, 2H, 5-CH2), 3.99 (s, 3H, OCH3), 5.33 (t, J = 4.0 Hz, 1H, 6-H), 6.38-6.41 (m, 2H), 6.44 (d, J = 8.8 Hz, 2H), 6.48 (s, 1H, 2-H), 6.70 (t, J = 7.2 Hz, 1H), 7.10 (t, J = 7.2 Hz, 2H), 7.14- 7.16 (m, 3H), 7.45-7.50 (m, 3H), 7.66 (d, J = 7.6 Hz, 1H), 7.94 (s, 1H), 8.10-8.15 (m, 2H), 8.22 (s, 1H), 10.30 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3) δ: 33.9 (C-5), 51.6, 55.3 (C-2), 57.2 (C-6), 96.9 (C-3), 113.2, 117.9, 121.5, 121.7, 122.0, 122.6, 125.8, 126.7, 129.3, 129.5, 129.8, 132.7, 137.3, 144.6, 145.9, 146.5, 148.7, 148.8, 155.7 (C-4), 168.2;

Anal. Calcd for C31H26N4O6 (550.58): C, 67.63; H, 4.76; N, 10.18; found C, 67.51; H, 4.68; N, 10.29.

Methyl 2,6-bis(4-nitrophenyl)-1-phenyl-4-(phenylamino)-1,2,5,6-tetrahydropyridine-3- carboxylate (122h)

Light yellow solid (0.176g, 32%); M.p. 239-241 ^oC. IR (KBr): 3356, 2950, 1660, 1593, 1518, 1499, 1346, 1257, 1072 cm^-1; ¹H NMR (400 MHz, CDCl3) δ: 2.85 (2H, d, J = 4.0 Hz), 3.95 (3H, s), 5.24-5.25 (1H, m), 6.37-6.42 (4H, m), 6.46 (1H, s), 6.68 (1H, t, J = 7.2 Hz), 7.07 (1H, d, J = 7.2 Hz), 7.09 (1H, d, J = 7.2 Hz), 7.13-7.17 (3H, m), 7.27 (2H, d, J = 8.8 Hz), 7.48 (2H, d, J = 8.4 Hz), 8.12 (2H, d, J = 8.8 Hz), 8.14 (2H,

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37

d, J = 8.8 Hz), 10.26 (1H, brs). ¹³C NMR (100 MHz, CDCl3) δ: 33.7, 51.6, 55.4, 57.5, 96.8, 113.1, 117.8, 123.9, 124.1, 125.7, 126.6, 127.5, 127.6, 129.4, 129.5, 137.3, 145.9, 146.9, 147.5, 149.9, 151.8, 155.7, 168.1. Anal. Calcd for C31H26N4O6 (550.58): C, 67.63; H, 4.76; N, 10.18; found C, 67.51; H, 4.69; N, 10.31.

Methyl 2,6-bis(4-methylphenyl)-1-(4-methylphenyl)-4-(4-methylphenylamino)-1,2, 5,6- tetrahydropyridine-3-carboxylate (122i)

Light yellow solid (0.351 g, 68%); M.p. 206-208 °C; IR (KBr): 3249 (NH), 1655, 1594 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 2.15 (s, 3H, ArCH3), 2.27 (s, 3H, ArCH3), 2.32 (s, 3H, ArCH3), 2.34 (s, 3H, ArCH3), 2.72 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H, 5-Ha), 2.82 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 3.91 (s, 3H, OCH3), 5.07 (d, J = 4.0 Hz, 1H, 6- H), 6.18 (d, J = 8.0 Hz, 2H), 6.35 (s, 1H, 2-H), 6.43 (d, J

= 8.0 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.0 Hz, 2H), 7.03-7.09 (m, 6H), 7.20 (d, J = 8.0 Hz, 2H), 10.17 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 20.3, 21.0, 21.2, 21.3, 33.7 (C-5), 51.0, 55.1 (C-2), 58.0 (C-6), 97.7 (C-3), 113.0 (2C), 125.0, 126.1 (2C), 126.5 (2C), 126.7 (2C), 129.0 (2C), 129.4 (2C), 129.5 (4C), 135.4, 135.6, 135.8, 136.6, 140.1, 141.4, 145.1, 156.8 (C-4), 168.8 (C=O); Anal. Calcd for C35H36N2O2 (516.68): C, 81.36; H, 7.02; N, 5.42; found C, 81.24; H, 7.01; N, 5.53.

Methyl 2,6-bis(4-methylphenyl)-1-(4-methoxyphenyl)-4-(4-methoxyphenylamino)-1,2,5, 6-tetrahydropyridine-3-carboxylate (122j)

White solid (0.406 g, 74%); M.p. 230-231 °C; IR (KBr):

3442, 1657, 1611 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 2.31 (s, 3H, ArCH3), 2.33 (s, 3H, ArCH3), 2.62 (dd, J = 2.8 Hz, J = 15.2 Hz, 1H, 5-Ha), 2.77 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 3.65 (s, 3H, ArOCH3), 3.74 (s, 3H, ArOCH3), 3.89 (s, 3H, OCH3), 5.00 (d, J = 2.8 Hz, 1H, 6-H), 6.21 (d, J = 9.2 Hz, 2H), 6.26 (s, 1H, 2-H), 6.43 (d, J = 9.2 Hz, 2H), 6.60 (d, J = 9.2 Hz, 2H), 6.64 (d, J = 9.2 Hz, 2H), 7.02-7.09 (m, 6H), 7.16 (d, J = 8.0 Hz, 2H), 10.08 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 21.2, 21.3, 33.8 (C-5), 51.0, 55.6, 55.7, 55.8 (C-2), 58.1 (C-6), 97.3 (C-3), 114.1 (2C), 114.2, 114.3, 114.7 (2C), 126.6 (2C), 126.9 (2C), 128.0 (2C), 129.0 (2C), 129.4 (2C), 131.0, 135.9,

Chapter II Experimental Section

38

136.7, 140.4, 141.5, 141.9, 151.0 (C-4), 157.2, 157.9, 168.9 (C=O); Anal. Calcd for C35H36N2O4 (548.69): C, 76.62; H, 6.61; N, 5.11.; found C, 76.56; H, 6.55; N, 5.26.

Methyl 2,6-bis(4-methylphenyl)-1-(4-bromophenyl)-4-(4-bromophenylamino)-1,2,5,6- tetrahydropyridine-3-carboxylate (122k)

Light yellow solid (0.440g, 68%); M.p. 230-232 °C; IR (KBr): 3446, 1650, 1605 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 2.32 (s, 3H, ArCH3), 2.34 (s, 3H, ArCH3), 2.70 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H, 5-Ha), 2.84 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 3.93 (s, 3H, OCH3), 5.06 (d, J

= 3.6 Hz, 1H, 6-H), 6.13 (d, J = 8.4 Hz, 2H), 6.31 (s, 1H, 2-H), 6.38 (d, J = 9.2 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 7.07-7.15 (m, 8H), 7.20 (d, J = 8.4 Hz, 2H), 10.17 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 21.2, 21.3, 33.6 (C-5), 51.3, 55.2 (C-2), 58.1 (C-6), 98.9 (C-3), 108.4, 114.7 (2C), 119.2, 126.4 (2C), 126.6 (2C), 127.4 (2C), 129.2 (2C), 129.6 (2C), 131.7 (2C), 132.1 (2C), 136.3, 137.1, 137.2, 139.2, 140.2, 146.1, 155.6 (C-4), 168.6 (C=O); Anal.

Calcd for C33H30N2O2Br2 (646.42): C, 61.32; H, 4.68; N, 4.33; found C, 61.23; H, 4.57;

N, 4.46.

Methyl 2,6-bis(4-methylphenyl)-1-(4-nitrophenyl)-4-(4-nitrophenylamino)-1,2,5,6- tetrahydropyridine-3-carboxylate (122l)

Yellow solid (0.295 g, 51%); M.p. 253-255 °C; IR (KBr):

1658, 1587 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 2.34 (s, 6H, 2 x ArCH3), 2.94 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H, 5- Ha), 3.06 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 3.99 (s, 3H, OCH3), 5.27 (d, J = 3.2 Hz, 1H, 6-H), 6.43 (d, J = 9.2 Hz, 2H), 6.48 (s, 1H, 2-H), 6.54 (d, J = 9.6 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 7.13 (s, 6H), 7.97 (d, J = 9.6 Hz, 2H), 8.00 (d, J = 9.2 Hz, 2H), 10.55 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 21.2, 21.3, 33.8 (C-5), 52.0, 55.8 (C-2), 58.5 (C-6), 102.0 (C-3), 112.3 (2C), 123.1 (2C), 125.1 (2C), 125.9 (2C), 126.1 (2C), 126.2 (2C), 129.7 (2C), 130.0 (2C), 137.2, 137.5, 137.9, 138.1, 138.3, 144.1 (2C), 151.9, 153.3 (C-4), 168.3 (C=O); Anal. Calcd for C33H30N4O6

(578.62): C, 68.50; H, 5.23; N, 9.68; found C, 68.39; H, 5.14; N, 9.88.

Methyl 2,6-bis(4-methylphenyl)-1-butyl-4-(butylamino)-1,2,5,6-tetrahydropyridine-3- carboxylate (122m)

N NH

OMe O

Me Me

Br Br

N NH

OMe O

Me Me

NO2

O2N

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39

Light yellow solid (0.215 g, 48%); M.p. 158-160 °C; IR (KBr): 3428, 1649, 1597 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 0.79 (t, J = 7.2 Hz, 3H, CH3), 0.98 (t, J = 7.2 Hz, 3H, CH3), 1.10 -1.23 (m, 2H, CH2), 1.26-1.36 (m, 2H, CH2), 1.43-1.52 (m, 2H, CH2), 1.60-1.68 (m, 2H, CH2), 2.08-2.15 (m, 2H, CH2), 2.30 (s, 3H, ArCH3), 2.32 (s, 3H, ArCH3), 2.51 (dd, J = 5.2 Hz, J = 17.2 Hz, 1H, 5-Ha), 2.60 (dd, J = 11.2 Hz, J = 17.2 Hz, 1H, 5-Hb), 3.24-3.38 (m, 2H), 3.55 (s, 3H, OCH3), 3.85 (dd, J = 5.2 Hz, J = 11.6 Hz, 1H, 6-H), 4.92 (s, 1H, 2-H), 7.08 (t, J = 7.6 Hz, 4H), 7.17 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 9.22 (t, J = 4.8 Hz, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 14.1, 14.3, 20.5, 20.6, 21.3 (2C), 25.6, 31.1, 32.5 (C-5), 42.1, 44.7, 50.6, 52.5 (C-2), 58.6 (C-6), 87.9 (C-3), 127.3 (2C), 128.4 (2C), 128.8 (2C), 128.9 (2C), 135.6, 136.4, 139.3, 142.4, 159.7 (C-4), 171.4; Anal. Calcd for C29H40N2O2 (448.64): C, 77.64; H, 8.99; N, 6.24; found C, 77.51; H, 8.91; N, 6.37.

Methyl 2,6-bis(4-methylphenyl)-1-benzyl-4-(benzylamino)-1,2,5,6-tetrahydropyridine-3- carboxylate (122n)

Light yellow solid (0.284 g, 55%); M.p. 172-173 °C; IR (KBr): 3272, 1650, 1594 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 2.28 (s, 3H, ArCH3), 2.30 (s, 3H, ArCH3), 2.62 (dd, J = 5.2 Hz, J = 17.2 Hz, 1H, 5-Ha), 2.73 (dd, J = 11.6 Hz, J = 17.2 Hz, 1H, 5-Hb), 3.32 (d, J = 13.6 Hz, 1H, CHaHb), 3.37 (d, J = 13.6 Hz, 1H, CHaHb), 3.46 (s, 3H, OCH3), 4.02 (dd, J = 5.2 Hz, J = 11.2 Hz, 1H, CHaHb), 4.57 (dd, J = 6.0 Hz, J = 15.6 Hz, 1H, CHaHb), 4.63 (dd, J = 6.4 Hz, J = 15.6 Hz, 1H, 6-H), 4.73 (s, 1H, 2-H), 7.08 (t, J = 8.0 Hz, 4H), 7.20 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 7.32 (t, J = 8.0 Hz, 4H), 7.37-7.40 (m, 6H), 9.67 (t, J

= 6.0 Hz, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 21.3, 25.5, 46.3, 49.7, 50.6, 52.2, 58.1, 89.3, 126.9, 127.0 (2C), 127.4 (2C), 127.6, 128.3 (2C), 128.4 (2C), 128.8 (2C), 129.0 (2C), 129.1 (4C), 135.8, 136.7, 138.7, 139.1, 140.5, 141.9, 159.0 (C-4), 171.3;

Anal. Calcd for C35H36N2O2 (516.69): C, 81.36; H, 7.02; N, 5.42.; found C, 81.22; H, 7.07; N, 5.57.

Ethyl 2,6-bis(4-methylphenyl)-1-phenyl-4-(phenylamino)-1,2,5,6-tetrahydropyridine-3- carboxylate (122o)

N NH

OMe O

Me Me

Chapter II Experimental Section

40

White solid (0.362 g, 72%); M.p. 228-231 °C; IR (KBr):

1649, 1592 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 1.46 (t, J

= 7.2 Hz, 3H, CH2CH3), 2.32 (s, 3H, ArCH3), 2.33 (s, 3H, ArCH3), 2.76 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H, 5-Ha), 2.86 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 4.26-4.36 (m, 1H, OCHaHb), 4.40-4.51 (m, 1H, OCHaHb), 5.11 (d, J = 2.4 Hz, 1H, 6-H), 6.30 (d, J = 7.6 Hz, 2H), 6.40 (s, 1H, 2-H), 6.53 (d, J = 8.8 Hz, 2H), 6.59 (t, J = 7.2 Hz, 1H), 7.02-7.10 (m, 11H), 7.22 (d, J = 8.0Hz, 2H), 10.29 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 15.0, 21.2, 21.3, 33.8 (C-5), 55.0 (C-2), 58.1 (C-6), 59.8, 98.5 (C-3), 113.1 (2C), 116.1, 125.7, 125.9 (2C), 126.5 (2C), 126.7 (2C), 128.9 (2C), 129.0 (2C), 129.1 (2C), 129.4 (2C), 135.9, 136.8, 138.2, 139.9, 141.2, 147.2, 156.2 (C- 4), 168.4 (C=O); Anal. Calcd for C34H34N2O2 (502.65): C, 81.24; H, 6.82; N, 5.57;

found C, 81.13; H, 6.76; N, 5.69.

Allyl 2,6-bis(4-methylphenyl)-1-phenyl-4-(phenylamino)-1,2,5,6-tetrahydropyridine -3- carboxylate (122p)

Light yellow solid (0.329 g, 64%); M.p. 186-188 °C; IR (KBr) : 3242, 1658, 1591 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 2.31 (s, 3H, ArCH3), 2.32 (s, 3H, ArCH3), 2.76 (dd, J = 2.4 Hz, J = 15.2 Hz, 1H, 5-Ha), 2.86 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 4.80 (ddt, J = 1.6 Hz, J = 5.6 Hz, J = 13.6 Hz, 1H, CHaHb), 4.87 (ddt, J = 1.6 Hz, J = 5.6 Hz, J = 13.6 Hz, 1H, CHaHb), 5.10 (d, J = 3.6 Hz, 1H, 6-H), 5.31 (dq, J = 1.2 Hz, J = 10.4 Hz, 1H, =CHaHb), 5.45 (dq, J = 1.2 Hz, J = 17.2 Hz, 1H, =CHaHb), 6.06-6.15 (m, 1H, =CH), 6.30 (dd, J = 2.4 Hz, J = 8.0 Hz, 2H), 6.43 (s, 1H, 2-H), 6.52 (d, J = 8.4 Hz, 2H), 6.58 (t, J = 7.2 Hz, 1H), 7.02-7.15 (m, 11H), 7.21 (d, J = 8.0 Hz, 2H), 10.26 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 21.2, 21.3, 33.9 (C-5), 55.1 (C-2), 58.1 (C-6), 64.5, 98.2 (C-3), 113.1 (2C), 116.2, 117.8, 125.8, 126.0 (2C), 126.5 (2C), 126.8 (2C), 128.98 (2C), 129.04 (2C), 129.1 (2C), 129.4 (2C), 133.3, 136.0, 136.8, 138.1, 139.8, 141.2, 147.2, 156.8 (C-4), 168.0 (C=O); Anal. Calcd for C35H34N2O2 (514.67): C, 81.68;

H, 6.66; N, 5.44.; found C, 81.56; H, 6.57; N, 5.51.

Tert-butyl2,6-bis(4-methylphenyl)-1-phenyl-4-(phenylamino)-1,2,5,6-tetrahydropyridine- 3-carboxylate (122q)

N NH

OEt O

Me Me

N NH

O O

Me Me

TH-1136_07612204

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41

Light yellow solid (0.308 g, 58%); M.p. 171-173 °C; IR (KBr): 3447, 1648, 1592 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 1.64 (s, 9H, CMe3), 2.31(s, 3H, ArCH3), 2.33 (s, 3H, ArCH3), 2.74 (dd, J = 2.8 Hz, J = 15.2 Hz, 1H, 5- Ha), 2.82 (dd, J = 5.6 Hz, J = 15.2 Hz, 1H, 5-Hb), 5.08 (d, J = 3.2 Hz, 1H, 6-H), 6.29 (d, J = 7.2 Hz, 2H), 6.35 (s, 1H, 2-H), 6.51 (d, J = 8.4 Hz, 2H), 6.58 (t, J = 7.2 Hz, 2H), 7.03-7.09 (m, 11H), 7.23 (d, J = 8.0 Hz, 2H), 10.25 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 21.2, 21.3, 29.0 (3C), 33.8 (C-5), 55.4 (C-2), 58.2 (C-6), 80.1 (CMe3), 100.2 (C-3), 113.1 (2C), 116.1, 125.4, 125.7 (2C), 126.6 (2C), 126.7 (2C), 128.9 (2C), 129.1 (4C), 129.4 (2C), 135.8, 136.7, 138.5, 140.0, 141.5, 147.4, 155.3 (C-4), 168.4 (C=O); Anal. Calcd for C36H38N2O2 (530.71): C, 81.48; H, 7.22; N, 5.28.; found C, 81.32; H, 7.31; N, 5.37.

Ethyl 2,6-bis(4-chlorophenyl)-1-phenyl-4-(phenylamino)-5-ethyl-1,2,5,6-tetrahydropyri dine -3-carboxylate (122r)

White solid (0.160 g, 28%); M.p. 239-241 °C; IR (KBr):

1655, 1594 cm^-1; ¹H NMR (400 MHz, CDCl3): δ 0.18 (t, J

= 7.2 Hz, 3H, CH3 ), 0.67-0.76 (m, 1H, CHaHb), 0.77-0.85 (m, 1H, CHaHb), 1.22 (t, J = 7.2 Hz, 3H, CH3), 3.04 (m, 1H, 5-H), 4.15-4.07 (m, 1H, CHaHb), 4.33-4.25 (m, 1H, CHaHb), 4.86 (d, J = 4.0 Hz, 1H, 6-H), 5.99 (s, 1H, 2-H), 6.78 (d, J = 8.0 Hz, 2H), 7.12-7.25 (m, 10H), 7.34 (d, J = 8.4 Hz, 2H), 7.38-7.43 (m, 4H), 10.78 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl3): δ 12.1, 14.6, 22.2, 43.1 (C-5), 60.0, 61.7 (C-2), 63.8 (C-6), 95.6 (C-3), 116.8 (2C), 119.2, 126.3, 126.6 (2C), 128.4 (2C), 128.5 (4C), 128.9 (2C), 129.0 (2C), 129.6 (2C), 132.4, 132.7, 139.1, 139.9, 145.8, 151.2, 161.8 (C-4), 169.2 (C=O); Anal. Calcd for C34H32N2O2Cl2 (571.54): C, 71.45; H, 5.64; N, 4.90; found: C, 71.34; H, 5.53; N, 5.02.

XRD for Compound 122l

Complete crystallographic data of compound 122l for the structural analysis has been deposited with the Cambridge Crystallographic Data Centre, CCDC No. 775694. Copies of this information may be obtained free of charge from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: +44-

1223-336033, e-mail: deposit@ccdc.cam.ac.uk or via: www.ccdc.cam.ac.uk).

N NH

O O

Me Me

N NH

O O

Cl Cl

Chapter II Experimental Section

42

 Table 3 Crystal data and structures refinement for the compounds 122l, for atomic coordinates and equivalent isotropic displacement parameters and bond angles, please check the CIF.

Parameters Compound 122l

Formula C33H30N4O6

CCDC number 775694

Formula weight 578.61

T (K) 296 K

Wavelength (Å) 0.71073

Crystal system Triclinic

Space group P -1

a (Å) 6.9024(5)Å

b (Å) 11.3349(8)Å

c (Å) 20.6948(14)Å

 (°) 75.901(4)º

 (°) 89.398(4)º

 (°) 72.491(4)º

V (ų) 1494.14(19) ų

Z 2

Dcalcd (g m^–3) 1.286/cm³

 (mm^–1) 0.090 mm^-1

F(0 0 0) 608.0

Reflection collected 7546

Unique reflections 6974

Goodness-of-fit (GOF)^a on F² 1.025

R [I > 2(I)] ^bR1= 0.1502, ^cwR2= 0.1842

R indices (all data) b

R1= 0.0602, ^cwR2= 0.1418

           

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Chapter II Experimental Section

43

1H  NMR  (400  MHz,  CDCl³):  Methyl  2,6‐bis(4‐methylphenyl)‐1‐phenyl‐4‐  

(phenylamino)‐1,2,5,6‐tetrahydropyridine‐3‐carboxylate (122a) 

13C  NMR  (100  MHz,  CDCl3):  Methyl  2,6‐bis(4‐methylphenyl)‐1‐phenyl‐4  (phenylamino)‐1,2,5,6‐tetrahydropyridine‐3‐carboxylate(122a) 

  Figure 9.

N NH

OMe O

Me Me

N NH

OMe O

Me Me

Chapter II Experimental Section

44

1H NMR (400 MHz, CDCl³):  Methyl 2,6‐bis(3,4,5‐trimethoxyphenyl)‐1‐phenyl‐4‐

(phenylamino)‐1,2,5,6‐tetrahydropyridine‐3‐carboxylate (122f)

1 3C  NMR (100 MHz,  CDCl³):  Methyl  2,6‐bis(3,4,5‐trimethoxyphenyl)‐1‐phenyl‐4‐

(phenylamino)‐1,2,5,6‐tetrahydropyridine‐3‐carboxylate(122f)  

Figure 10.

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Chapter II Experimental Section

45

1H NMR (400 MHz, CDCl³): Methyl 2,6‐bis(4‐methylphenyl)‐1‐(4‐methylphenyl)‐4‐

(4‐methylphenylamino)‐1,2, 5,6‐tetrahydropyridine‐3‐carboxylate (122i)  

13C NMR (100 MHz, CDCl³): Methyl 2,6‐bis(4‐methylphenyl)‐1‐(4‐methylphenyl)‐4‐

(4‐methylphenylamino)‐1,2, 5,6‐tetrahydropyridine‐3‐carboxylate (122i)

Figure 11.

N NH

OMe O

Me Me

Me Me

N NH

OMe O

Me Me

Me Me

Chapter II Experimental Section

46

1H NMR (400 MHz, CDCl³): Methyl 2,6‐bis(4‐methylphenyl)‐1‐(4‐nitrophenyl)‐4‐(4‐

nitrophenylamino)‐1,2,5,6‐tetrahydropyridine‐3arboxylate(122l) 

13C NMR (100 MHz, CDCl³): Methyl 2,6‐bis(4‐methylphenyl)‐1‐(4‐nitrophenyl)‐4‐(4‐

nitrophenylamino)‐1,2,5,6‐tetrahydropyridine‐3‐carboxylate(122l)

Figure 12.

N NH

OMe O

Me Me

NO₂ O₂N

N NH

OMe O

Me Me

NO2

O2N

TH-1136_07612204

Chapter II Experimental Section

47

1H NMR (400 MHz, CDCl³): Ethyl 2,6‐bis(4‐methylphenyl)‐1‐phenyl‐4‐(phenylamino)‐

1,2,5,6‐tetrahydropyridine‐3‐carboxylate (122o)

1H  NMR  (400  MHz,  CDCl³):    Ethyl  2,6‐bis(4‐methylphenyl)‐1‐phenyl‐4‐

(phenylamino)‐1,2,5,6‐tetrahydropyridine‐3‐carboxylate(122o) 

Figure 13.

N NH

OEt O

Me Me

N NH

OEt O

Me Me

HN NH

OR O

R ¹

C H A P T E R I II :

R es ul ts and D is c us s ion

Hydrogen-bond-mediated regioselective