very rapidly. Mannich bases were prepared by the reaction of substituted piperazine
or piperidine derivatives and chlorokojic acid in MeOH with 37% formaline. The
mixture was stirred vigorously for 15-25 min at room temperature. The resulting
precipitate was collected by filtration and washed with cold MeOH. Formation of
the desired new Mannich base derivatives were confirmed on the basis of elemental
analysis, and the structures of the compounds were supported by spectral data.
Chlorokojic acid was synthesized as described before.10-12,15 Yield 60%, m.p. 166-
167°C.6-(Chloromethyl)-3-hydroxy-2-((4-(4-iodophenyl)piperazin-1-yl)methyl)-
4H-pyran-4-one (Compound 5) C17H18ClIN2O3, Yield: 56%; mp: 182-3°C; %CHN
Found (Calculated): C 44.65 (44.32), H 3.91 (3.94), N 6.61 (6.08); IR ν (cm-1):
1
1630 (C=O), 1456 (C=C), 1202 (C-O); H-NMR (DMSO-d6, 400 MHz) δ ppm:
2.60 (4H; t; J= 4.8; piperazine-H2', H6'), 3.13 (4H; t; J= 4.8; piperazine-H3',H5'),
3.62 (2H; s; -CH2-), 4.66 (2H; s; ClCH2-), 6.55 (1H; s; H5), 6.76 (2H; d; J= 9.2;
Ar-H2'', H6''), 7.46 (2H; d; J= 9.2; Ar-H3'', H5''), 9.22 (1H; s; -OH); 13C-NMR
(DMSO, 400 MHz) δ ppm: 42.11, 48.35, 52.77, 54.02, 81.32, 113.12, 118.49,
137.93, 144.82, 148.14, 151.19, 161.93, 174.15; ESI-MS (m/z): 399 (100%), 461
(M++H), 463 (M++H+2), 483 (M++Na). Ethyl 4-((6-(chloromethyl)-3-hydroxy-4-
oxo-4H-pyran-2-yl)methyl)piperazine-1-carboxylate
(Compound
20)
C14H19ClN2O5, Yield: 63%; mp: 136-7°C; %CHN Found (Calculated): C 50.59
(50.84), H 5.63 (5.79), N 8.38 (8.47); IR ν (cm-1): 1679 (C=O), 1424 (C=C), 1220
1
(C-O); H-NMR (DMSO-d6, 400 MHz) δ ppm: 1.67 (3H; t; J= 7.0; -CH3), 2.44
(4H; t; J= 5.2; piperazine-H2', H6'), 3.36 (4H; t; J= 5.2; piperazine-H3',H5'), 3.60
(2H; s; -CH2-), 4.02 (2H; q; J= 6.8; -CH2CH3), 4.65 (2H; s; ClCH2-), 6.55 (1H; s;
H5), 9.19 (1H; brs; -OH); 13C-NMR (DMSO, 400 MHz) δ ppm: 15.22, 42.10,
43.93, 52.62, 53.10, 61.39, 113.12, 144.86, 147.90, 155.23, 161.94, 174.16; ESI-
MS (m/z): 331 (M++H), 333 (M++H+2), 353 (M++Na, 100%). Benzyl 4-((6-
(chloromethyl)-3-hydroxy-4-oxo-4H-pyran-2-yl)methyl)piperazine-1-carboxylate
(Compound 21) C19H21ClN2O5, Yield: 64%; mp: 141-2°C; %CHN Found
(Calculated): C 57.86 (58.09), H 5.25 (5.39), N 7.07 (7.13); IR ν (cm-1): 1679
1
(C=O), 1446 (C=C), 1225 (C-O); H-NMR (DMSO-d6, 400 MHz) δ ppm: 2.45
(4H; t; J= 4.8; piperazine-H2', H6'), 3.40 (4H; m; piperazine-H3',H5'), 3.60 (2H; s; -
CH2-), 4.65 (2H; s; ClCH2-), 5.07 (2H; s; -CH2COO-), 6.55 (1H; s; H5), 7.28-7.38
(5H; m; Ar-H), 9.20 (1H; brs; -OH); 13C-NMR (DMSO, 400 MHz) δ ppm: 42.10,
44.15, 52.64, 54.01, 66.89, 113.12, 128.20, 128.50, 129.09, 137.57, 144.82, 148.05,
155.05, 161.92, 174.17; ESI-MS (m/z): 393 (M++H), 395 (M++H+2), 415 (M++Na,
100%).
1-((6-(Chloromethyl)-3-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-4-
phenylpiperidine-4-carbonitrile (Compound 22) C19H19ClN2O3, Yield: 71%; mp:
156-7°C; %CHN Found (Calculated): C 64.35 (63.60), H 5.39 (5.34), N 7.91
1
(7.81); IR ν (cm-1): 1660 (C=O), 1455 (C=C), 1200 (C-O); H-NMR (DMSO-d6,
400 MHz) δ ppm: 1.99-2.56 (8H; m; piperidine); 3.68 (2H; s; -CH2-), 4.66 (2H; s;
ClCH2-), 6.56 (1H; s; H5), 7.34-7.54 (5H; m; Ar-H); 9.24 (1H; brs; -OH); 13C-NMR
(DMSO, 400 MHz) δ ppm: 36.15, 42.09, 42.29, 50.69, 54.03, 113.19, 122.67,
126.33, 128.75, 129.71, 140.82, 144.87, 148.19, 161.95, 174.19; ESI-MS (m/z):
381 (100%, M++Na), 359 (M++H), 361 (M++H+2). 6-(Chloromethyl)-3-hydroxy-2-
((4-phenyl-5,6-dihydropyridin-1(2H)-yl)methyl)-4H-pyran-4-one (Compound 23)
C18H18ClNO3, Yield: 76%; mp: 165-6°C; %CHN Found (Calculated): C 64.67
(65.16), H 5.33 (5.47), N 4.16 (4.22); IR ν (cm-1): 1622 (C=O), 1456 (C=C), 1198
1
(C-O); H-NMR (DMSO-d6, 400 MHz) δ ppm: 2.49-3.19 (6H; m; pyridine), 3.69
(2H; s; -CH2-), 4.67 (2H; s; ClCH2-), 6.14 (1H; t; J= 3.6; pyridine), 6.55 (1H; s;
H5), 7.22-7.42 (5H; m; Ar-H); 13C-NMR (DMSO, 400 MHz) δ ppm: 27.99, 42.13,
5