4.2.2 General procedure 2 for the synthesis compounds (5, 7, 9 and 11)
2-Methyl-1,4-naphthoquinone (1) (Vitamin K3) and N-substituted nucleophiles (4, 6, 8 and 10) were refluxed in 50 ml of absolute ethanol in presence of Na2CO3 (0.2 g) for 8 hours. The reaction mixture was monitoring by (TLC) until disappearance of starting material. The mixture was extracted using 30 ml of chloroform, washed three times with water, then dried using Na2SO4. Evaporator system was used to remove the extra amount of solvent. The crude dark residue was purified by column chromatography and dried using vacuum oven at the end [39].
Synthesis of 2-(4-benzhydrylpiperazin-1-yl)-3-methylnaphthalene-1,4-dione (3)
According to procedure 1, 1.0 g (5.8 mmol) of 2-methyl-1,4-naphthoquinone (1) was reacted with 1-(diphenylmethyl)piperazine (2) (1.46 g, 5.7 mmol) in chloroform with presence of TEA. The product (3) was synthesized as a new compound.
Compound 3: Red solid, yield: 0.349 g, (15%), Rf :0.90 [EtAc/CHCl3(1:7 v/v)]; M.p: 100.5–101.0°C. FT-IR (cm− 1): v = 3219 (C-Harom), 2979, 2904, (C-Haliph), 1661 (C = O), 1590 (C = C). 1H NMR (ppm): δ = 2.00 (s, 3H, CH3), 2.51 (s, br, 4H, Hpiper), 3.43 (br, s, 4H, Hpiper), 4.32 (s, 1H,-CH>), 7.27–7.77 (m, 10H, Harom), 7.80 (d, J = 5.44 Hz, 2H, Hnaphth), 8.00 (dd, J = 6.84, 2.93 Hz, 2H, Hnaphth). 13C(APT) NMR (ppm): δ = 13.60 (CH3), 52.91 (CH2-N-CH2), 76.80 (–CH<), 125.75, 126.19, 126.55, 127.58, 127.73, 127.77, 128.01, 128.3, 128.50, 128.63, 128.85, 130.07, 132.53, 134.8 (CHarom, Carom), 168.24 (= C-N), 183.62, 185.40 (C = O); C28H26N2O2 (Mw= 422.53 g/mol). Calcd., %: C 79.59; H 6.20; N 6.63. Found, % : C 79.32; H 6.61; N 6.99. MS (+ ESI): m/z = 423.1[M]+.
According to procedure 2, 1.0 g (5.8 mmol) of 2-methyl-1,4-naphthoquinone (1) was refluxed with 0.89 g (5.8 mmol) of 2,4-dimethoxyaniline (4) in absolute ethanol with presence of Na2CO3 (0.2 g). The product (5) was obtained as a new compound.
Compound 5: Red oil, yield: 0.456 g, (24%), Rf: 0.50 [CHCl3/hexane(1:4 v/v)]. FT-IR (cm− 1): ν = 3338 (N-H), 3063 (C-Harom), 2970, 2913, (C-Haliph), 1724, 1662 (C = O), 1597,1567 (C = C). 1H NMR (ppm): δ = 1.73 (s, 3H, CH3), 3.38 (s, 3H, -OCH3), 3.85 (s, 3H, -OCH3) 6.44–6.48 (m, 2H, Harom), 6.81 (d, J = 9.27 Hz, 1H, Harom), 7.22 (s, 1H, -NH), 7.61–7.73 (m, 2H, CHnaphth), 8.04–8.08 (dd, J = 0.98, J = 8.19 Hz, 2H, CHnaphth). 13C(APT) NMR (ppm): δ = 13.31 (CH3), 55.52, 55.70 (O-CH3), 98.95, 103.36, 116,41, 121.96, 124.36, 126.07, 130.49, 132.09, 133.46, 134.25, 143.07 ppm (CHarom, Carom), 153.55, 157.80 ppm (= C-O), 182.53, 184.21 ppm (C = O). C19H17NO4. (Mw = 323.35 g/mol). Calcd., %: C 70.58; H 5.30; N 4.33. Found, % : C 70.32; H 5.21; N 4.48. MS (+ ESI): m/z = 324.1[M + H] +.
According to procedure 2, 1.0 g (5.8 mmol) of 2-methyl-1,4-naphthoquinone (1) was refluxed with 0.70 g (5.6 mmol) of 4-methoxyaniline (6) in absolute ethanol with presence of Na2CO3 (0.2 g). The product (7) was obtained as a new compound.
Compound 7: Purple solid, yield: 0.351 g (21%), Rf: 0.80 [CHCl3/hexane(1:4 v/v)]; M.p.: 69.5–70.0°C. FT-IR (cm− 1): ν = 3248 (N-H), 2966, 2916, (C-Haliph), 1718, 1664 (C = O), 1594, 1563 (C = C), 1072, (C-O). 1H NMR (ppm): δ = 1.63 (s, 3H, CH3), 3.74 (s, 3H, -OCH3), 6.87–6.80 (m, 2H, Harom), 6.89–6.91 (m, 2H, Harom), 7.27 (s, 1H, NH), 7.55–7.66 (m, 2H, CHnaphth), 8.00-8.05 (m, 2H, CHnaphth). 13C(APT) NMR (ppm): δ = 13.22 (CH3), 55.45 (O-CH3), 114.12, 116.73, 124.86, 126.12, 130.83, 132.22, 133.39, (CHarom−Carom), 143.10 (= C-N)naphth,156.48 (C-O)ph, 182.60, 184.35 (C = O). C18H15NO3(Mw =293.32 g/mol). Calcd., %: C 73.71; H 5.15; N 4.78. Found, % : C 73.32; H 5.61; N 4.99. MS (+ ESI): m/z = 294.1 [M + H] +.
Synthesis of 2-(4-benzylpiperidin-1-yl)-3-methylnaphthalene-1,4-dione (9)
According to procedure 2, 1.0 g (5.8 mmol) of 2-methyl-1,4-naphthoquinone (1) was reacted with 1.0 g (5.7 mmol) of 4-benzylpiperidine (8) in 50 ml of absolute ethanol at room temperature with presence of Na2CO3 (0.2 g), Product (9) was obtained as a new compound.
Compound 9: Red oil, yield: 0.612 g (32%); Rf: 0.71 [EtAc/PET(1:6 v/v)]. FT-IR (cm− 1): v = 2956, 2922, 2853 (C-Haliph), 1722, 1667(C = O), 1596 (C = C). 1H NMR (ppm): δ = 1.04–1.21, 1.26–1.36 (m, 4H, (CH2-CH-CH2)piperi), 1.61–1.69 (m, 1H,, (CH2-CH-CH2)piperi), 2.11 (s, 3H, CH3), 2.50 (2H, d, J = 0.86 Hz, CH2), 3.10, 4.32 (m, 4H, (CH2-N-CH2)piperi), 7.07–7.20 (m, 5H, CHarom), 7.50–7.64 (m, 2H, CHnaphth.), 7.84–7.94 (m, 2H, CHnaphth). 13C(APT) NMR (ppm): δ = 13.58 (CH3), 33.21 (CH2-CH-CH2)piperi, 37.99 (CH2-CH-CH2)piperi, 43.32 (CH2), 52.00 (CH2-N-CH2)piper, 125.68, 126.12, 126.34, 128.24, 128.84, 129.01, 132.13, 132.48, 133.19, 133.67 (CHarom, Carom), 140.26 (CH2-Cph) 153.10 (= C-N), 183.90, 185.45 (C = O). C23H23NO2 (Mw =345.44 g/mol). Calcd., %: C 79.97; H 6.71; N 4.05. Found, % : C 80.32; H 6.61; N 3.99. MS (+ ESI): m/z = 346.30 [M]+.
Synthesis of 2-methyl-3-(4-(2-((3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino)ethyl)piperazin-1-yl)naphthalene-1,4-dione (11)
According to procedure 2, 1.0 g (5.8 mmol) of 2-methyl-1,4-naphthoquinone (1) was reacted with 0.75g (5.8 mmol) of 1-(2-aminoethyl)piperazine (10) in absolute ethanol with presence of Na2CO3 (0.2 g). The product (11) was obtained as a new compound.
Compound 11: Red solid, yield: 0.558 g, (24%), Rf : 0.62 [EtAc/CHCl3(1:5 v/v)]: M.p.: 177.5–178.0°C. FT-IR (cm− 1): ν = 3310 (N-H), 3078 (C-Harom), 2968, 2906, (C-Haliph), 1661 (C = O), 1594, 1563 (C = C). 1H NMR (ppm): δ = 1.94, (s, 3H, CH3), 2.05 (s, 3H, CH3), 2.60 (s, 4H, Hpiper), 2.70 (t, J = 7.32, 2H, CH2-NH), 3.40 (t, J = 4.8 Hz, 4H, Hpiper), 3.65 (m, 2H, CH2-Npiper), 6.36 (br, s, 1H, N-H), 7.51–7.61 (m, 4H, CHnaphth), 7.91–7.98 (m, 4H, CHnaphth). 13C(APT) NMR (ppm): δ = 11.06, 13.60 (CH3), 41.57 (CH2-NH), 51.20, 53.48 (CH2-N)piper 57.16 (N-CH2-), 125.78, 126.20, 128.71, 130.51, 131.82, 132.67, 133.48, 134. (CHarom, Carom), 146.61, (= C-NH), 151.51 (= C-N), 182.56, 183.48, 183.65, 185.47 (C = O. C28H27N3O4, (Mw = 469.54 g/mol). Calcd., %: C 71.62; H 5.80; N 8.95. Found, % : C 71.32; H 6.01; N 9.09. MS (+ ESI): m/z = 470.2 [M] +.