Supporting Information for

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1 S 1 Supporting Information for Novel and Convenient Synthesis of Substituted Quinolines by Copper or PalladiumCatalyzed Cyclodehydration of 1-(2-Aminoaryl)-2-yn-1-ols Bartolo Gabriele,*, Raffaella Mancuso, # Giuseppe Salerno, # Giuseppe Ruffolo, # Pierluigi Plastina # Dipartimento di Scienze Farmaceutiche, Università della Calabria, 8736 Arcavacata di Rende (Cosenza), Italy, and # Dipartimento di Chimica, Università della Calabria, 8736 Arcavacata di Rende (Cosenza), Italy b.gabriele@unical.it Table of Contents Page S2 Tables S1 and S2 Page S3 General Experimental Methods Pages S3-S4 Preparation and Characterization of 2-Amino-3-methoxyacetophenone (1c) Page S4S5 Preparation and Characterization of 2-Amino-5-chloroacetophenone (1d) Pages S5S6 Preparation and Characterization of 2-(2-Aminophenyl)oct-3-yn-2-ol (2aa) Pages S6S1 Characterization Data of Products Page S11 References and Footnotes Pages S12S29 Copy of 1 H and 13 C NMR spectra

2 S 2 TABLE S1. Cyclodehydration reactions of 2-(2-aminophenyl)oct-3- yn-2-ol 2aa in MeOH to give 2-butyl-4-methylquinoline 3aa in the presence of different catalytic systems a Entry Catalyst t (h) Conversion of 2aa (%) b Yield of 3aa (%) c 1 ZnCl ZnI PdCl 2 +1KCl PdI 2 +1KI CuCl CuI CuI CuCl 2 2H 2 O CuCl 2 2H 2 O CuCl CuCl CuCl (78) 13 None 5 d a All reactions were carried out in MeOH at C with a substrate concentration of.22 mmol of 2aa per ml of MeOH in the presence of 2 mol % of catalyst. b Based on starting 2aa, by GLC. c GLC yield (isolated yield) based on 2aa. d Unidentified chromatographically immobile materials were formed under these conditions. TABLE S2. Cyclodehydration reactions of 2-(2- aminophenyl)oct-3-yn-2-ol 2aa in different solvents to give 2- butyl-4-methylquinoline 3aa in the presence of CuCl 2 as the catalyst a a Entry Solvent t (h) Conversion of 2aa (%) b Yield of 3aa (%) c 14 Dioxane DME DME (46) 17 MeCN DMA 1 19 DMA 5 65 (58) All reactions were carried out at C with a substrate concentration of.22 mmol of 2aa per ml of MeOH in the presence of 2 mol % of CuCl 2. b Based on starting 2aa, by GLC. c GLC yield (isolated yield) based on 2aa.

3 S 3 General Experimental Methods Melting points are uncorrected. 1 H NMR and 13 C NMR spectra were recorded at 25 C in CDCl 3 solutions at 3 or 5 MHz and 75 or 126 MHz, respectively, with Me 4 Si as internal standard. Chemical shifts () and coupling constants (J) are given in ppm and in Hz, respectively. IR spectra were taken with an FT-IR spectrometer. Mass spectra were obtained using a GC-MS apparatus at 7 ev ionization voltage. Microanalyses were carried out at our analytical laboratory. All reactions were analyzed by TLC on silica gel F 254 and by GLC using a gas chromatograph and capillary columns with polymethylsilicone + 5% phenylsilicone as the stationary phase. Column chromatography was performed on silica gel (7-23 mesh). Evaporation refers to the removal of solvent under reduced pressure. 2-Aminoacetophenone 1a and 2-aminobenzophenone 1b were commercially available and were used as received. 2-Amino-3-methoxyacetophenone 1c was prepared by nitration of commercially available 3-methoxyacetophenone followed by reduction, as described in the literature. 1 2-Amino-5-chloroacetophenone 1d was prepared by nitration of commercially available 3-chloroacetophenone followed by reduction, as described below. Pure 2-(2-aminophenyl)oct-3-yn- 2-ol (2aa) was prepared and characterized as described below. Preparation and Characterization of 2-Amino-3-methoxyacetophenone (1c) Nitration of 3-methoxyacetophenone to give 2-nitro-3-methoxyacetophenone. 1,2 To concd. HNO 3 (12 ml) maintained at 5 C was quickly added 3-methoxyacetophenone (2. g, 13.3 mmol) with stirring. After additional stirring at 5 C for 5 min., the mixture was allowed to warm up to room temperature ant then stirred at room temperature for 54 h. Ice followed by Et 2 O (1 ml) was added. Phases were separated and the aqueous phase was extracted with Et 2 O (3 1 ml). The collected organic layers were washed with water and then dried over Na 2 SO 4. The solvent was evaporated and the residue was taken up with EtOH. Crystallization at C followed by filtration afforded, after drying, 2-nitro-3-methoxyacetophenone as a colorless solid, mp C (lit C) (778. mg, 3%). IR (KBr): = 1689 (m), 15 (w), 1545 (s), 1458 (m), 1379 (m), 1313 (m), 1291 (s), 148 (m), 977 (m), 864 (m), 789 (m), 614 (w) cm -1 ; 1 H NMR (5 MHz): = 7.55 (dd, J = 8.2, 7.7, 1 H), 7.41 (dd, J = 7.7, 1.1, 1 H), 7.29 (dd, J = 8.2, 1.1, 1 H), 3.92 (s, 3 H),

4 S (s, 3 H); 13 C NMR (126 MHz): = 195.7, 151.4, 131.4,.9, 117., 56.8, 28.; GC-MS: m/z = 195 (17) [M + ], 1 (), 153 (24), 119 (14), 95 (16), 93 (12), 91 (16), 78 (35), 77 (3), 76 (), 75 (), 74 (17), 67 (1), 65 (22). Reduction of 2-nitro-3-methoxyacetophenone to give 2-amino-3-methoxyacetophenone 1c. The method of Robbins was employed. 3 A mixture of the 2-nitro-3-methoxyacetophenone (2.22 g, 11.4 mmol), Sn powder (3.81 g, 32.1 mmol), and concd. HCl (8.8 ml) was allowed to reflux for 4 h with stirring. After cooling to C, NaOH (pellets) was added to basic ph. Et 2 O (15 ml) was added and phases were separated. The aqueous phase was extracted with Et 2 O (2 15 ml) and the collected organic layers were dried over Na 2 SO 4. After filtration, the solvent was evaporated to give a brown-yellow solid, which was purified by column chromatography (SiO 2, 7:3 hexane-acoet) to give 2-amino-3-methoxyacetophenone as a pale yellow solid, mp C (lit C) (1.41 g, 75%). IR (KBr): = 3476 (s), 3348 (s), 1636 (s), 1545 (s), 1453 (m), 14 (w), 1362 (w), 12 (w), 1243 (m), 1223 (m), 142 (w), 967 (w), 736 (w) cm -1 ; 1 H NMR (5 MHz): = 7.31 (dd, J = 8.2, 1.1, 1 H), 6.82 (dd, J = 7.7, 1.1, 1 H), 6.59 (s, br, 2 H), 6.55 (dd, J = 8.2, 7.7, 1 H), 3.84 (s, 3 H), 2.55 (s, 3 H); 13 C NMR (126 MHz): =.7, 147.2, 141.6, 123.3, 117.5, 114.,112.8, 55.7, 28.1; GC-MS: m/z = 165 (88) [M + ], 15 (), 122 (37), 17 (14), 14 (22), 79 (14), 78 (14), 77 (17), 65 (19). Preparation and Characterization of 2-Amino-5-chloroacetophenone (1d) Nitration of 3-chloroacetophenone to give 5-chloro-2-nitroacetophenone. The method of Robbins was employed. 3 To concd. HNO 3 (8 ml) maintained at C was added in portions with stirring concd. H 2 SO 4 ( ml). After additional stirring at C for 45 min., 3- chloroacetophenone (8. g, 52. mmol) was added very slowly at C with vigorous stirring. After additional stirring for 2 h at C, ice was added followed by AcOEt (15 ml). Phases were separated and the aqueous phase was extracted with AcOEt (2 15 ml). The collected organic layers were evaporated and Et 2 O (15 ml) was added to the residue. The orange precipitate was recovered by decantation and then crystallized 2 times from MeOH at ca. 18 C. The crude 5- chloro-2-nitroacetophenone (3.1 g) thus obtained was then used as such for the next step. Reduction of 5-chloro-2-nitroacetophenone to give 2-amino-5-chloroacetophenone 1d. The method of Robbins was employed. 3 A mixture of the 5-chloro-2-nitroacetophenone obtained above, Sn powder (5.36 g, 45.2 mmol), concd. HCl (12.5 ml) was allowed to reflux for 4 h with stirring.

5 S 5 After cooling to C, NaOH (pellets) was added to basic ph. Et 2 O ( ml) was added and phases were separated. The aqueous phase was extracted with Et 2 O (2 ml) and the collected organic layers were dried over Na 2 SO 4. After filtration, the solvent was evaporated to give a brown-yellow solid, which was purified by column chromatography (SiO 2, 8:2 hexane-acoet) to give a pale yellow solid, mp C (lit C) (3.97 g, 45% based on 5-chloro-2-nitroacetophenone). IR (KBr): = 3457 (s), 3324 (s), 1654 (s), 1617 (s), 1577 (m), 1544 (m), 1474 (m), 1362 (w), 1231 (m), 11 (w), 958 (w), 824 (w), 628 (w) cm -1 ; 1 H NMR (5 MHz): = 7.62 (d, J = 2.7, 1 H), 7.16 (dd, J = 8.8, 2.7, 1 H), 6.57 (d, J = 8.8, 1 H), 6.3 (s, br, 2 H), 2.53 (s, 3 H); GC-MS: m/z = 171 (29) [M + + 2], 169 (84) [M + ], 156 (33), 154 (), 128 (11), 126 (38), 99 (), 9 (18), 65 (13). Preparation and Characterization of 2-(2-Aminophenyl)oct-3-yn-2-ol (2aa) To a suspension of Mg turnings (7 mg, 28.8 mmol) in anhydrous THF (2. ml), maintained under nitrogen and under reflux, was added pure EtBr (.5 ml) to start the formation of the Grignard reagent. The remaining bromide was added dropwise (ca. min) in THF solution (1.5 ml of EtBr in 15. ml of THF; total amount of EtBr added: 2.92 g, 26.8 mmol). The mixture was then allowed to reflux for additional min. After cooling, the solution of EtMgBr thus obtained was transferred under nitrogen to a dropping funnel and was added dropwise to a solution of the 1- hexyne (2. g, 26.8 mmol) in anhydrous THF (7. ml) at C with stirring. After additional stirring at C for 15 min, the mixture was allowed to warm up to room temperature, maintained at 5 C for 2 h, and then used as such for the next step. 2-Aminoacetophenone 1a (1. g, 8.9 mmol) was dissolved under nitrogen in anhydrous THF (7. ml) and then added dropwise to the solution of the 1-hexynylmagnesium bromide in THF (prepared as described above) at 5 C under nitrogen. After stirring at 5 C for 1 h, the mixture was cooled to room temperature. Saturated NH 4 Cl was added with stirring to achieve weakly acidic ph. After additional stirring at room temperature for 15 min., AcOEt (ca. ml) was added and phases were separated. The aqueous phase was extracted with AcOEt (3 3 ml), and the collected organic layers were washed with brine to neutral ph and eventually dried over Na 2 SO 4. After filtration, the solvent was evaporated and the crude product was purified by column chromatography on silica gel (9:1 hexane-acoet) to give pure 2aa as a yellow oil (1.16 g, % based on 1a). Partial decomposition of 2aa usually occurred during the purification procedure, which somewhat affected the final yield obtained. IR (film): = 3451 (m), 3365 (s), 2957 (s), 2932 (s), 2871 (m), 22 (vw), 1614 (s), 1493 (m), 1455 (m), 1368 (w), 137

6 S 6 (m), 1237 (m), 1159 (w), 192 (m), 153 (m), 95 (w), 751 (s) cm -1 ; 1 H NMR (3 MHz): = 7.48 (dd, J = 7.8, 1.5, 1 H), 7.7 (ddd, J = 7.8, 7.4, 1.5, 1 H), 6.73 (ddd, J = 7.8, 7.4, 1.3, 1 H), 6.63 (dd, J = 7.8, 1.3, 1 H), 4.37 (s, br, 2 H), 2.26 (t, J = 7., 2 H), 1.82 (s, 3 H), (m, 4 H),.91 (t, J = 7.2, 3 H) (Note: the OH signal was too broad to be detected); 13 C NMR (75 MHz): = 144.3, 128.7, 126.4, 118.3, 117.8, 85.9, 83.4, 7.3, 3.7, 28.8, 22., 18.4, 13.6; GC-MS: m/z = 217 (44) [M + ], 2 (15), 199 (18), 184 (19), 171 (12), 17 (53), 158 (), 157 (97), 156 (66), 155 (22), 154 (21), 144 (25), 143 (13), 13 (38), 129 (28), 128 (3), (), 118 (1), 117 (11), 115 (12), 92 (23), 77 (12), 65 (19). Characterization Data of Products 2-Butyl-4-methylquinoline (3aa). Yield: 1.42 g, starting from 1. g of 2-aminoacetophenone 1a (%) (Table 1, entry 21). Yellow oil. IR (film): = 2955 (m), 2929 (s), 2869 (m), 14 (s), 1561 (w), 1465 (m), 1379 (w), 1259 (w), 1123 (w), 861 (w), 758 (m) cm -1 ; 1 H NMR (3 MHz): = 8.5 (ddd, J = 8.5, 1.3,.7, 1 H), (m, 1 H), 7.65 (ddd, J = 8.5, 7., 1.5, 1 H), 7.47 (ddd, J = 8.3, 7., 1.3, 1 H), 7.12 (q, J = 1., 1 H), (m, 2 H), 2.65 (d, J = 1., 3 H), (m, 2 H), (m, 2 H),.96 (t, J = 7.3, 3 H); 13 C NMR (75 MHz): = 162.8, 147.7, 144.2, 129.3, 129., 126.8, 125.4, 123.6, 122.1, 39., 32.2, 22.8, 18.7, 14.; GC-MS: m/z = 199 (1) [M + ], 184 (13), 171 (6), 17 (29), 158 (23), 157 (), 156 (9), 116 (7), 115 (12); anal. calcd for C 14 H 17 N (199.29): C, 84.37; H, 8.; N, 7.3; found C, 84.41; H, 8.59; N, Butyl-4-phenylquinoline (3ba). Yield: 1.86 g, starting from 1.76 g of 2-aminobenzophenone 1b (%) (Table 1, entry 22). Yellow oil. IR (film): = 2956 (s), 2929 (m), 2871 (w), 1593 (s), 1557 (m), 149 (m), 1444 (m), 8 (m), 1179 (m), 129 (m), 881 (m), 766 (s), 72 (s) cm -1 ; 1 H NMR (3 MHz): 8.12 (ddd, J = 8.4, 1.2,.6, 1 H), 7.86 (ddd, J = 8.4, 1.4,.6, 1 H), 7.66 (ddd, J = 8.4, 6.9, 1.4, 1 H), (m, 5 H), 7. (ddd, J = 8.4, 6.9, 1.2, 1 H), 7.23 (s, 1 H), (m, 2 H), (m, 2 H), (m, 2 H),.96 (t, J = 7.3, 3 H); 13 C NMR (75 MHz): = 162.6, 148.5, 148.4, 138.3, 129.5, 129.2, 128.5, 128.3, 125.7, 125.6, 125.3, 121.6, 39.1, 32.2, 22.7, 14.; GC-MS: m/z = 261 (<.5) [M + ], 232 (15), 2 (19), 219 (), 218 (9), 217 (7); anal. calcd for C 19 H 19 N (261.36): C, 87.31; H, 7.33; N, 5.36; found C, 87.39; H, 7.31; N, Butyl-8-methoxy-4-methylquinoline (3ca). Yield: 1.55 g, starting from 1.47 g of 3-methoxy-2- aminoacetophenone 1c (76%) (Table 1, entry 24). Yellow oil. IR (film): = 2954 (s), 2927 (s),

7 S (m), 16 (m), 1562 (m), 158 (m), 1465 (s), 1442 (w), 7 (w), 12 (s), 115 (m), 146 (m), 747 (m) cm -1 ; 1 H NMR (5 MHz): 7.48 (dd, J = 8.4, 1.1, 1 H), 7.37 (dd, J = 8.4, 7.7, 1 H), 7.16 (s, 1 H), 7. (dd, J = 7.7, 1.1, 1 H), 4.4 (s, 3 H), (m, 2 H), 2.61 (s, 3 H), (m, 2 H), 1.45 (sextuplet, J = 7.5, 2 H),.96 (t, J = 7.5, 3 H); 13 C NMR (126 MHz): = 161.7, 155.4, 144., 139.6, 127.9, 125.3, 122.5, 115.5, 17.4, 56., 39.2, 32.3, 22.9, 19.2, 14.; GC-MS: m/z = 229 (12) [M + ], 228 (29), (29), 188 (18), 187 (), 185 (13), 172 (39), 17 (24), 169 (23), 157 (11), 115 (11); anal. calcd for C 15 H 19 NO (229.32): C, 78.56; H, 8.35; N, 6.11; found C, 78.66; H, 8.33; N, Butyl-6-chloro-4-methylquinoline (3da). Yield: 1.69 g, starting from 1.51 g of 5-chloro-2- aminoacetophenone 1d (81%) (Table 1, entry 25). Yellow oil. IR (film): = 29 (m), 2928 (w), 2535 (w), 14 (m), 1437 (w), 1384 (s), 1262 (m), 188 (s), 124 (s), 877 (w), 2 (s) (m) cm -1 ; 1 H NMR (3 MHz): 8.13 (d, J = 9., 1 H), 7.95 (d, J = 2.2, 1 H), 7.67 (dd, J = 9., 2.2, 1 H), 7.28 (q, J =.9, 1 H), (m, 2 H), 2.7 (d, J =.9, 3 H), (m, 2 H), 1.44 (sextuplet, J = 7.4, 2 H),.96 (t, J = 7.4, 3 H); 13 C NMR (75 MHz): = 162.6, 146.5, 143.7, 132.5, 131.1, 129.2, 127.7, 123., 122.9, 37.6, 31.8, 22.6, 18.8, 13.8; GC-MS: m/z = 235 (<.5) [M + + 2], 233 (2) [M + ], 232 (3), 218 (15), 6 (11), 4 (32), 193 (59), 192 (26), 191 (), 156 (9), 155 (9), 154 (14), 141 (12), (14), 128 (8), 127 (8), 115 (8), 75 (5); anal. calcd for C 14 H 16 ClN (233.74): C, 71.94; H, 6.9; Cl, 15.17; N, 5.99; found C, 71.85; H, 6.92; Cl, 15.18; N, Methyl-2-phenylquinoline (3ab). Yield: 1.42 g, starting from 1. g of 2-aminoacetophenone 1a (73%) (Table 1, entry 28). Yellow solid, C, lit C. IR (KBr): = 3 (m), 1597 (s), 1551 (m), 159 (w), 1495 (w), 1451 (m), 1348 (m), 179 (w), 129 (w), 861 (w), 769 (s), 694 (s) cm -1 ; 1 H NMR (3 MHz): = (m, 3 H), (m, 1 H), 7.69 (ddd, J = 8.4, 6.9, 1.5, 1 H), (m, 1 H), (m, 4 H), 2.71 (d, J = 1., 3 H); 13 C NMR (75 MHz): = 157., 148.1, 144.8, 139.8, 13.2, 129.3, 129.2, 128.7, 127.5, 127.2, 126., 123.6, 119.7, 19.; GC- MS: m/z = 219 () [M + ], 218 (42), 217 (23), 216 (8), 5 (13), 4 (71), 19 (12); anal. calcd for C 16 H 13 N (219.28): C, 87.64; H, 5.98; N, 6.39; found C, 87.58; H, 5.99; N, ,4-Diphenylquinoline (3bb). Yield: 1.7 g, starting from 1.76 g of 2-aminobenzophenone 1b (68%) (Table 1, entry 3). Yellow solid, mp C, lit C. IR (KBr): = 354 (m), 159 (s), 1546 (m), 1489 (m), 1445 (m), 7 (m), 1358 (m), 1231 (m), 174 (m), 131 (m), 89 (m), 77 (s), 72 (s) cm -1 ; 1 H NMR (3 MHz): 8.24 (ddd, J = 8.5, 1.1,.6, 1 H), (m, 2 H), (m, 1 H), 7.78 (s, 1 H), 7.68 (ddd, J = 8.5, 6.9, 1.5, 1 H), (m, 9 H); 13 C

8 S 8 NMR (75 MHz): = 156.8, 149.2, 148.8, 139.6, 138.4, 13.1, , , 129.3, 128.8, 128.6, 128.4, 127.6, 126.3, 125.8, 125.6, 119.3; GC-MS: m/z = 281 (76) [M + ], 2 (), 278 (7), 2 (16), 176 (6), 139 (1); anal. calcd for C 21 H 15 N (281.35): C, 89.65; H, 5.37; N, 4.98; found C, 89.71; H, 5.35; N, Methoxy-4-methyl-2-phenylquinoline (3cb). Yield: 2. g, starting from 1.47 g of 2-amino-3- methoxyacetophenone 1c (9%) (Table 1, entry 32). Yellow solid, mp C. IR (KBr): = 1 (m), 1552 (w), 1493 (m), 1468 (s), 7 (w), 135 (w), 1257 (s), 11 (m), 145 (m), 96 (m), 773 (w), 744 (m), 78 (m) cm -1 ; 1 H NMR (5 MHz): = (m, 2 H), 7.72 (s, 1 H), (m, 5 H), 7.4 (d, J = 7.7, 1 H), 4.7 (s, 3 H), 2.71 (s, 3 H); 13 C NMR (126 MHz): = 156., 155.8, 144.7,.1, 139.9, 129., 128.7, 128.4, 127.6, 126.1,.2, 115.5, 17.8, 56.1, 19.5; GC-MS: m/z = 249 (92) [M + ], 248 (), 2 (51), 219 (28), 218 (17), 217 (12), 4 (15), 115 (1), 77 (17); anal. calcd for C 17 H 15 NO (249.31): C, 81.9; H, 6.6; N, 5.62; found C, 81.98; H, 6.5; N, Chloro-4-methyl-2-phenylquinoline (3db). Yield: 1.76 g, starting from 1.51 g of 2-amino-5- choroacetophenone 1d (78%) (Table 1, entry 33). Yellow solid, mp 89-9 C, lit C. IR (KBr): = 1599 (s), 1545 (w), 1491 (m), 1446 (w), 1436 (w), 1384 (s), 1348 (s), 1283 (w), 191 (m), 128 (w), 881 (m), 777 (m), 698 (s), 684 (m) cm -1 ; 1 H NMR (5 MHz): = (m, 3 H), 7.94 (d, J = 2.2, 1 H), 7.71 (s, br, 1 H), 7.65 (dd, J = 9.3, 2.2, 1 H), (m, 3 H), 2.72 (d, J = 1.1, 3 H); 13 C NMR (126 MHz): = 157., 145.8, 144.9, 138.6, 132.1, 131.3, 13.6, 129.8, 128.9, 128., 127.6, 122.8,.6, 19.; GC-MS: m/z = 255 (33) [M + + 2], 254 (27), 253 () [M + ], 252 (22), 2 (15), 238 (46), 218 (1), 217 (24), 216 (14), 3 (11), 19 (23); anal. calcd for C 16 H 12 ClN (253.73): C, 75.74; H, 4.77; Cl, 13.97; N, 5.52; found C, 75.81; H, 4.76; Cl, 13.95; N, tert-Butyl-4-methylquinoline (3ac). Yield: 1.33 mg, starting from 1. g of 2- aminoacetophenone 1a (75%) (Table 1, entry 37). Yellow oil. IR (film): = 2956 (s), 2917 (m), 2863 (m), 12 (m), 1557 (m), 156 (m), 1448 (m), 1363 (w), 1153 (m), 117 (m), 932 (w), 863 (w), 757 (s) cm -1 ; 1 H NMR (3 MHz): = 8.6 (ddd, J = 8.4, 1.3,.7, 1 H), (m, 1 H), 7.63 (ddd, J = 8.4, 6.9, 1.5, 1 H), 7.46 (ddd, J = 8.2, 6.9, 1.3, 1 H), 7.33 (q, J =.8, 1 H), 2.66 (d, J =.8, 3 H), 1.45 (s, 9 H); 13 C NMR (75 MHz): = 168.9, 147.3, 143.6, 129.9, 128.7, 126.5, 125.3, 123.3, 118.8, 37.9, 3.1, 18.9; GC-MS: m/z = 199 (36) [M + ], 198 (3), 184 (), 185 (15), 168 (9), 157 (42), 143 (19), 115 (13); anal. calcd for C 14 H 17 N (199.29): C, 84.37; H, 8.; N, 7.3; found C, 84.33; H, 8.62; N, 7.5.

9 S 9 2-tert-Butyl-4-phenylquinoline (3bc). Yield: 1.63 g, starting from 1.76 g of 2-aminobenzophenone 1b (7%) (Table 1, entry 38). Colorless solid, mp C, lit C. IR (KBr): = 3 (m), 159 (s), 1554 (m), 1488 (m), 1447 (m), 7 (m), 1363 (m), 1252 (m), 116 (m), 127 (m), 886 (m), 839 (w), 779 (m), 762 (s), 77 (s) cm -1 ; 1 H NMR (3 MHz): 8.13 (ddd, J = 8.4, 1.2,.6, 1 H), 7.84 (ddd, J = 8.4, 1.5,.6, 1 H), 7.64 (ddd, J = 8.4, 6.9, 1.5, 1 H), (m, 6 H), 7.39 (ddd, J = 8.4, 6.9, 1.2, 1 H), 1.49 (s, 9 H); 13 C NMR (75 MHz): = 168.7, 148.1, 147.9, 138.8, 129.8, 129.6, 128.9, 128.4, 128.1, 125.7, 125.3, 125., 118.4, 38.1, 3.1; GC-MS: m/z = 261 (44) [M + ], 2 (28), 247 (), 246 (), 2 (1), 219 (48), 5 (13), 4 (18); anal. calcd for C 19 H 19 N (261.36): C, 87.31; H, 7.33; N, 5.36; found C, 87.26; H, 7.35; N, tert-Butyl-8-methoxy-4-methylquinoline (3cc). Yield: 1.57 g, starting from 1.47 g of 3- methoxy-2-aminobenzophenone 1c (77%) (Table 1, entry 39). Yellow oil. IR (film): = 2959 (s), 2866 (m), 1598 (m), 1588 (m), 1557 (m), 1494 (m), 9 (s), 1362 (m), 1336 (w), 1258 (s), 2 (w), 148 (m), 932 (w), 87 (w), 731 (m) cm -1 ; 1 H NMR (5 MHz): 7.5 (distorted d, J = 8.2, 1 H), (m, 2 H), 7.1 (d, J = 7.7, 1 H), 4.5 (s, 3 H), 2.65 (s, 3 H), 1.48 (s, 9 H); 13 C NMR (126 MHz): = 167.7, 155.8, 143.6, 139.2, 127.8, 125.4, 119.6, 115.5, 18.2, 56.5, 38.2, 3.2, 19.5; GC-MS: m/z = 229 (99) [M + ], 228 (), 215 (12), 214 (73), 213 (17), 212 (), 21 (12), (63), 199 (73), 198 (47), 197 (1), 196 (33), 187 (11), 185 (13), 184 (32), 183 (15), 173 (23), 169 (1), 115 (17), 17 (11), 77 (1); anal. calcd for C 15 H 19 NO (229.32): C, 78.56; H, 8.35; N, 6.11; found C, 78.62; H, 8.33; N, Methylquinoline (3ad). Yield:.93 g, starting from 1. g of 2-aminoacetophenone 1a (73%) (Table 2, entry 42). Yellow oil. IR (film): = 1596 (m), 15 (m), 1524 (s), 1452 (s), 131 (m), 1251 (m), 841 (m), 757 (s) cm -1 ; 1 H NMR (3 MHz): 8.74 (d, J = 4.3, 1 H), (m, 1 H), 7.92 (dd, J = 8.3, 1.4, 1 H), 7.66 (ddd, J = 8.4, 6.9, 1.4, 1 H), 7.5 (ddd, J = 8.3, 6.9, 1., 1 H), 7.14 (d, J = 4.3, 1 H), 2.62 (s, 3 H); 13 C NMR (75 MHz): = 15., 147.8, 144.3, 129.9, 129.1, 128.2, 126.2, 123.8, 121.8, 18.6; GC-MS: m/z = 143 () [M + ], 142 (33), 117 (9), 116 (15), 115 (39), 89 (1); anal. calcd for C 1 H 9 N (143.19): C, 83.88; H, 6.34; N, 9.78; found C, 83.75; H, 6.36; N, Phenylquinoline (3bd). Yield: 1. g, starting from 1.76 g of 2-aminobenzophenone 1b (66%) (Table 2, entry 45). Yellow solid, mp C, lit C. IR (KBr): = 1584 (m), 158 (w), 1491 (m), 1391 (m), 1277 (w), 13 (w), 851 (m), 769 (s), 74 (s), 612 (m) cm -1 ; 1 H NMR (3 MHz): 8.94 (d, J = 4.4, 1 H), 8.18 (ddd, J = 8.5, 1.1,.6, 1 H), (m, 1 H), 7.71 (ddd, J = 8.5, 7., 1.5, 1 H), (m, 6 H), 7.32 (d, J = 4.4, 1 H); 13 C NMR (75 MHz): = 149.9, 148.7,

10 S , 138., 129.8, 129.6, 129.3, 128.6, 128.4, 126.8, 126.6, 125.9, 121.3; GC-MS: m/z = 5 (), 4 (97), 3 (1), 178 (13), 177 (12), 176 (3), 151 (12), 12 (14), 88 (12); anal. calcd for C 15 H 11 N (5.25): C, 87.77; H, 5.; N, 6.82; found C, 87.83; H, 5.38; N, (1-Methoxy-1-methylhept-2-ynyl)phenylamine (4ac). Yield: 6 mg, starting from 1. g of 2- aminoacetophenone 1a (3%) (Table 1, entry 35). Yellow oil. IR (film): = 347 (m), 3371 (m), 2969 (s), 2934 (m), 2221 (vw), 1614 (s), 1492 (m), 1459 (m), 1364 (w), 131 (w), 1263 (m), 185 (s), 148 (w), 859 (w), 75 (m) cm -1 ; 1 H NMR (3 MHz): = 7.57 (dd, J = 7.7, 1.5, 1 H), 7.8 (ddd, J = 7.9, 7.3, 1.5, 1 H), 6.7 (ddd, J = 7.7, 7.3, 1.2, 1 H), 6.58 (dd, J = 7.9, 1.2, 1 H), 4.45 (s, br, 2 H), 3.24 (s, 3 H), 1.78 (s, 3 H), 1.32 (s, 9 H); 13 C NMR (75 MHz): = 144.7, 129.2, 128.8, 124.4, 117.3, 116.5, 96.7, 78.6, 78.5, 51.9, 31.1, 27.7, 27.6; GC-MS: m/z = 231 (38) [M + ], 216 (28), (21), 199 (63), 198 (16), 185 (19), 184 (), 17 (17), 169 (39), 168 (26), 167 (13), 158 (42), 157 (17), 156 (11), 154 (15), 144 (23), 143 (21), 142 (11), 131 (13), 13 (34), 115 (9), 16 (6), 91 (9), 77 (1); anal. calcd for C 15 H 21 NO (231.33): C, 77.88; H, 9.15; N, 6.5; found C, 77.86; H, 9.13; N, 6.2.

11 S11 References and Footnotes (1) The only mononitrated product obtained by nitration of 3-methoxyacetophenone was 3- methoxy-2-nitroacetophenone, as confirmed by 1 H NMR. This product was obtained either by using the nitration procedure reported by Alford et. al., 2 or by using the procedure recently reported by Robbins et. al. 3 It is worth noting that in this latter case the Authors have indicated the structure of the mononitrated product as 5-methoxy-2-nitroacetophenone rather than 3-methoxy-2- nitroacetophenone. (2) Alford, E. J.; Irving, H.; Marsh, H. S.; Schofield, K. J. Chem. Soc. 1952, (3) Robbins, R. J.; Laman, D. M.; Falvey, D. E. J. Am. Chem. Soc. 1996, 118, (4) Ames, D. E.; Ansari, H. R.; France, A. D. G.; Lovesey, A. C.; Novitt, B.; Simpson, R. J. Chem. Soc. (C) 1971, (5) Georgarakis, E.; Schmid, H.; Hansen, H.-J. Helv. Chim. Acta 1979, 62, (6) Leonard, N. J.; Boyd, S. N., Jr. J. Org. Chem. 1946, 11, (7) Giezendanner, H.; Rosenkranz, H. J.; Hansen, H. J.; Schmid, H. Helv. Chim. Acta 1973, 56, (8) Al-Talib, M.; Jochims, J. C.; Wang, Q.; Hamed, A.; Ismail, A. E.-H. Synthesis 1992, (9) Makioka, Y.; Shindo, T.; Taniguchi, Y.; Takaki, K.; Fujiwara, Y. Synthesis 1995, 1 4. (1) Kobayashi, K.; Yoneda, K., Miyamoto, K.; Morikawa, O.; Konishi, H. Tetrahedron 4,, (11) Badger, G. M.; Cook, J. W.; Walker, T. J. Chem. Soc. 1948, 11 13

12 S12 Copy of 1 H and 13 C NMR spectra 2-Nitro-3-methoxyacetophenone O Me NO 2 OMe 1 HNMR (5 MHz, CDCl 3 ) I n t e g r a l CNMR (126 MHz, CDCl 3 )

13 S13 2-Amino-3-methoxyacetophenone O Me NH 2 OMe 1 c 1 HNMR (5 MHz, CDCl 3 ) I n t e g r a l CNMR (126 MHz, CDCl 3 )

14 S14 2-Amino-5-choroacetophenone Cl O Me NH 2 1 d 1 HNMR (5 MHz, CDCl 3 ) I n t e g r a l

15 S15 2-(2-Aminophenyl)oct-3-yn-2-ol Me OH NH 2 Bu 2aa 1 HNMR (3 MHz, CDCl 3 ) CNMR (75 MHz, CDCl 3 )

16 S16 2-Butyl-4-methylquinoline Me N Bu 3aa 1 HNMR (3 MHz, CDCl 3 ) CNMR (75 MHz, CDCl 3 )

17 S17 2-Butyl-4-phenylquinoline Ph N Bu 3ba 1 HNMR (3 MHz, CDCl 3 ) I n t e g r a l CNMR (75 MHz, CDCl 3 )

18 S18 2-Butyl-8-methoxy-4-methylquinoline Me N OMe Bu 3ca 1 HNMR (5 MHz, CDCl 3 ) I n t e g r a l CNMR (126 MHz, CDCl 3 )

19 S19 2-Butyl-6-chloro-4-methylquinoline Cl Me N Bu 3da 1 HNMR (3 MHz, CDCl 3 ) CNMR (75 MHz, CDCl 3 )

20 S 4-Methyl-2-phenylquinoline Me N Ph 3ab 1 HNMR (3 MHz, CDCl 3 ) I n t e g r a l CNMR (75 MHz, CDCl 3 )

21 S21 2,4-Diphenylquinoline Ph N Ph 3bb 1 HNMR (5 MHz, CDCl 3 ) I n t e g r a l CNMR (126 MHz, CDCl 3 )

22 S22 8-Methoxy-4-methyl-2-phenylquinoline Me N OMe Ph 3cb 1 HNMR (5 MHz, CDCl 3 ) I n t e g r a l CNMR (126 MHz, CDCl 3 )

23 S23 6-Chloro-4-methyl-2-phenylquinoline Cl Me N Ph 3db 1 HNMR (5 MHz, CDCl 3 ) CNMR (126 MHz, CDCl 3 )

24 S24 2-tert-Butyl-4-methylquinoline Me N t-bu 3ac 1 HNMR (3 MHz, CDCl 3 ) I n t e g r a l CNMR (75 MHz, CDCl 3 )

25 S25 2-tert-Butyl-4-phenylquinoline Ph N t-bu 3bc 1 HNMR (3 MHz, CDCl 3 ) I n t e g r a l CNMR (75 MHz, CDCl 3 )

26 S26 2-tert-Butyl-8-methoxy-4-methylquinoline Me N OMe t-bu 3cc 1 HNMR (5 MHz, CDCl 3 ) I n t e g r a l CNMR (126 MHz, CDCl 3 )

27 S27 4-Methylquinoline Me N 3ad 1 HNMR (3 MHz, CDCl 3 ) I n t e g r a l CNMR (75 MHz, CDCl 3 )

28 S28 4-Phenylquinoline Ph N 3bd 1 HNMR (3 MHz, CDCl 3 ) I n t e g r a l CNMR (75 MHz, CDCl 3 )

29 S29 2-(1-Methoxy-1-methylhept-2-ynyl)phenylamine Me OMe t-bu NH 2 4ac 1 HNMR (3 MHz, CDCl 3 ) CNMR (75 MHz, CDCl 3 )