1. A Facile One-Pot Synthesis of 1-Aryl-2-(dimethylaminomethyl)prop-2-en-1-ones from Aryl Methyl Ketones
2. Schreiber, J.; Maag, H.; Hashimoto, N.; Eschenmoser, A. Angew. Chem. 1971, 83, 355–357; Angew. Chem., Int. Ed. Engl. 1971, 10, 330–332.
3. For a recent review on the classical Mannich reaction, see: Tramontini, M.; Angiolini, L. Mannich Bases, Chemistry and Uses; CRC: Boca Raton, 1994.
4. For modern variants of the Mannich reaction, see: (a) Arend, M.; Risch, N. Angew. Chem. 1995, 107, 2861–2862; Angew. Chem., Int. Ed. Engl. 1995, 34, 2639–2640; (b) Arend, M.; Risch, N. Synlett 1997, 974–976; (c) Arend, M.; Westermann, B.; Risch, N. Angew. Chem. 1998, 110, 1097–1122; Angew. Chem., Int. Ed. Engl. 1998, 37, 1045–1068; (d) Arend, M.; Risch, N. Tetrahedron Lett. 1999, 40, 6205–6206.
5. General procedure: To a solution of 50 mmol phosphorus oxychloride in 20 ml of diethyl ether, 10 mmol of 3 or 6 was added and the ensuing solution stirred at ambient temperature. Dimethyl(methylene)ammonium chloride (20 mmol) was added after 2 h to the yellow solution. The resultant suspension was allowed to react overnight at ambient temperature while stirring was continued. In order to isolate the product the following two procedures were used with the same result: (a) if a solution was formed overnight, 20 ml of isopropanol was added to get rid of the excess phosphorus oxychloride and 20 mmol of perchloric acid (70%, aqueous solution), usually at this point precipitation occurred. If this was not the case, the solvent was removed in vacuo and 20 ml of isopropanol added to the residue. (b) In case of a suspension the solid was separated from the ethereous phosphorus oxychloride solution and 20 ml of isopropanol followed by 20 mmol of perchloric acid (70%, aqueous solution) was added to the residue under stirring. Thereafter, the crystals were obtained by filtration and subsequent washing with diethyl ether. Recrystallization from isopropanol. Analytical and spectroscopic data of some new compounds: 9a: 1H NMR (300 MHz, DMSO-d6): δ=2.87 (br s, 12H, 2×N(CH3)2); 3.49 (br s, 4H, 2×CH2); 3.68 (m, 1H, COCH); 7.13 (t, 1H arom, H-4); 7.36 (t, 1H arom, H-3, H-5); 7.70 (dd, 2H arom, H-2, H-6); 10.30 (br s, 2H, exchangeable with D2O, 2×NH); 11.06 (s, 1H, exchangeable with D2O, CONH). 13C NMR (75 MHz, DMSO-d6): δ=38.4 (CH), 42.7 (CH2), 43.0 (CH2), 56.1 (CH3), 119.7, 124.1, 128.6, 138.3 (CH arom.), 167.4 (CO). IR (KBr pellet, cm−1): ν=3353 (br m), 3033 (w), 2976 (w), 2689 (br s), 1686 (s), 1602 (m), 1547 (s), 1446 (br m), 1087 (s), 763 (s), 626 (s). 9d: 1H NMR (300 MHz, DMSO-d6): δ=2.87 (br s, 12H, 2×N(CH3)2); 3.39 (m, 4H, 2×CH2); 3.65 (m, 1H, COCH); 7.61 (m, 2H arom, H-2, H-6); 8.08 (d, 1H arom, H-5); 10.01 (br s, 2H, exchangeable with D2O, 2×NH); 11.46 (s, 1H, exchangeable with D2O, CONH). 13C NMR (75 MHz, DMSO-d6): δ=38.5 (CH), 43.0 (CH2), 56.1 (CH3), 119.8, 121.7, 125.6, 130.6, 130.8, 138.4 (CH arom.), 167.9 (CO). IR (KBr pellet, cm−1): ν=3370 (br m), 3020 (w), 2980 (w), 2670 (br s), 1679 (s), 1580 (s), 1540 (s), 1450 (br m), 1090 (s), 1030 (s), 740 (s), 640 (s). 9k: 1H NMR (300 MHz, DMSO-d6): δ=2.66 (d, 3H, NHCH3); 2.80 (br s, 12H, 2×N(CH3)2); 3.38 (br m, 5H, CH(CH)2); 8.12 (d, 1H, exchangeable with D2O, CONH); 10.18 (br s; 2H, exchangeable with D2O, 2×NH). 13C NMR (75 MHz, DMSO-d6): δ=25.9 (CH3), 37.4 (CH), 42.4 (CH2), 43.0 (CH2), 56.1 (CH3), 169.0 (CO). IR (KBr pellet, cm−1): ν=3272 (m), 2980 (w), 2670 (br s), 1660 (s), 1540 (m), 1441 (m), 1256 (w), 1070 (br s), 889 (w), 613 (s). 9l: 1H NMR (300 MHz, DMSO-d6): δ=1.09 (d, 6H, 2×CH3); 1.23 (m, 1H, CH); 2.80 (br s, 12H, 2×N(CH3)2); 3.31 (br m, 4H, 2×CH2); 3.84 (m, 1H, COCH); 8.58 (d, 1H, exchangeable with D2O, CONH); 10.16 (br s; 2H, exchangeable with D2O, 2×NH). 13C NMR (75 MHz, DMSO-d6): δ=21.9 (CH3), 37.6 (CH), 41.2 (CH), 42.1 (CH2), 43.3 (CH2), 56.1 (CH3), 167.8 (CO). IR (KBr pellet, cm−1): ν=3272 (m), 2972 (m), 2686 (br s), 1656 (s), 1554 (m), 1464 (m), 1244 (w), 1088 (br s), 896 (w), 626 (s).