ARKIVC 212 (viii) S1-S Supplementary Material An efficient method for the preparation of 2,2,4- trisubstituted 1,2- dihydroquinolines using catalytic amount Bi(Tf) as catalyst Zeynep Gültekin, a* Wolfgang Frey b a Çankırı Karatekin University, Department of Chemistry, 181, Çankırı, Turkey b University of Stuttgart, Institut für rganische Chemie, Pfaffenwaldring 55, D-7569 Stuttgart, Germany E-mail: zpgul66@hotmail.com Table of Contents 1. General Methods S1 2. General Procedure for the synthesis of 1,2-dihydroquinolines under room temperature S1. General Procedure for the synthesis of 1,2-dihydroquinolines under microvawe conditions S1 4. Characterization of products a-r and 4, 9 S2 5. 1 MR and 1 C MR Spectra of Compounds a-r and 4, 9 S11 General Methods. Acetonitrile, chloroform were distilled from calcium hydride immediately prior to use. DMF, toluene, nitromethane were distilled before use. All aniline derivatives, Bi(Tf), methyl pyruvate are commercially available. Compounds a, 16 n, o, i and c 17 previously reported in the literature. Column chromatography was performed using M silica gel (particle size.4-.6 mm). For thin-layer chromatography (TLC), silica gel coated aluminium plates (Merck, silica gel 6 F 254 ) were used and chromatography was performed using silica gel Merck 6 (particle size.6-.2 mm), visualised by UV irradiation. 1 -MR and 1 C-MR were recorded on a Mercury or 4 spectrometer in CDCl or MeD. Data are reported in the following order: chemical shift ( ) in ppm; multiplicities are indicated bs (broadened singlet), s (singlet), d (doublet), m (multiplet), dd (double doubled); coupling constants (J) are in ertz (z). 1 C MR spectra were acquired on a broad band decoupled mode. Mass spectra was conducted on GC-MS Shimadzu QP21 (column: Equity -5, length I.D. m.25 mm, df.25 μm, lot # 2889-U, Supelco). RMS were measured on a Finnigan MAT 95 or LTQ rbitrap XL spectrometer. IR spectra were measured in a Perkin-Elmer ATR apparatus and are reported in terms of frequency of absorption (cm -1 ). Microwave, CEM marked, Discover SP-D With explorer 12 ybrid was used. General procedure for the synthesis of 1,2-dihydroquinolines under room temperature The -Substituted aniline (1 mg, 1 eq) was dissolved in acetonitrile (1.5 ml) in a screwcapped test tube and Bi(Tf) (5 mol%,.5 eq) and methyl pyruvate (2.2 eq) was added to the mixture. This mixture were stirred at room temperature (For the time see: Table ) until the starting material was completely consumed as monitored by tlc. The resultant residue was direcly purified by flash chromatography on silica (EtAc:Cyclohexane 2:98). All solid products were recrystallized over pentan and ethyl acetate. General procedure for the synthesis of 1,2-dihydroquinolines under microvawe conditions -Substituted aniline (1 mg, 1 eq) was dissolved in acetonitrile (1.5 ml) then Bi(Tf) (5 mol%,.5 eq) and methyl pyruvate (2.2 eq) were added to the solution. This mixture were heated by microwave irradiation (1 bar, 15 watt, 1 o C, See for the time: Table 1,2 and ). Page S1
ARKIVC 212 (viii) S1-S The progress of the reaction was monitored through tlc. The resultant residue was direcly purified by flash chromatography on silica (EtAc:Cyclohexane 2:98). All solid products were recrystallized over pentan and ethyl acetate. By this method the following compounds were prepared. Characterization of products a-r and 4, 9 Dimethyl 8-acetyl-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (a) 16 C 6 5 1 4 7 8 9 1 2 C Yellow crystalline solid; yield (71%); R f.5 (2:1 Cyclohexane/EtAc); m.p: 11-12 o C. IR (KBr) 268 (), 1718, 169 (C) cm -1. 1 -MR ( Mz, CDCl ): s,, C ), s,, CC ),.76 (s,, CC ),.85 (s,, CC ), 6.59-6.64 (m, 1, Ar- ), 6.65-6.66 (d, 1, J 1.9 z, C=C), 7.65-7.68 (dd, 1, J 8.1 and 1.4 z, Ar- ), 7.9-8. (m, 1, Ar- ) 9.6 (bs, 1, ). C-MR (4 Mz, CDCl ): 28.1 (C ), 28.7 (CC ), 52.2, 52.9 (2xCC ), 58.6 (C2), 115.1 (C8), 116.7 (C6), 117.6 (C1), 127. (C7), 11.8 (C5). 12. (C), 12.7 (C4), 146. (C9), 165.7 (C), 172.9 (C), 2.4 (C). Anal. Calcd for C 16 17 5 : C, 6.6;, 5.65;, 4.62. Found: C, 6.41;, 5.8;, 4.61. MS m/z (EI).1 (M +, %), 245.1 (9), 244.1 (1), 228.1 (8), 226.1 (28), 185.1 (15), 167.1 (1), 142.1 ( 1), 115. (8), 59.2 (4). Dimethyl 6-phenoxy-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (b) 4 5 2 1 6 6 5 1 4 C 7 9 2 8 1 C Yellow solid; yield (77%); R f.4 (2:1 Cyclohexane/EtAc); m.p: 78-79 o C. IR (KBr) 79 (), 1721 (C) cm -1. 1 -MR (4 Mz, CDCl ): s,, C ),.76 (s,, CC ),.81 (s,, CC ), 4.49 (br, 1, ), 6.61-6.6 (d, 1, J 8. z, Ar- ), 6.7 (bs, 1, -C=C), 6.8-6.8 (dd, 1, J 8.7 and 2.6 z, Ar- ), 6.92-6.94 (m, 2, Ar- ), 6.98-7. (m, 1, Ar- ), 7.25-7.29 (m, 1, Ar- ), 7.61 (bs, 1, Ar-). C-MR (4 Mz, CDCl ): 27.4 (C ), 52.1, 52.8 (2xCC ), 58.7 (C2), 114.9 (C8), 117.1 (C7), 117. (C5), 118.6 (C1), 121.6 (C6 ). 121.9 (C2 ), 127.4 (C4 ), 129.4 (C and C5 ), 1.7 (C), 18.9 (C4), 148.2 (C9), 157. (C6), 158.6 (C1 ), 165.6 (C), 174.2 (C). Anal. Calcd for C 2 19 5 : C, 67.98;, 5.42;,.96. Found: C, 67.9;, 5.54;,.92; MS m/z (EI) 5.1 (M +, 4%), 295.1 (19), 294.1 (1), 25.1 (4), 77.2 (5), 59. (2). Page S2
ARKIVC 212 (viii) S1-S Dimethyl 6-methoxy-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (c) 17 C 7 6 C 5 1 4 8 9 1 2 C Yellow oil; yield (58%); R f. (2:1 Cyclohexane/EtAc). IR (kapilar) 68 (), 1726 (C) cm -1. 1 -MR (Mz, CDCl ): s,, C ),.72,.74,,85 (s, 9, CMe and 6-Me), 4.4 (bs, 1, ), 6.57-6.59 (d,1, J 8.6z, Ar-), 6.69-6.7 (dd, 1, J 8.6 and 2.8 z, Ar-), 6.74 (bs, 1, -C=C), 7.48-7.49 (d, 1, 2.8 z, Ar-). C-MR ( Mz, CDCl ): 26.9 (C ), 52., 52.7 (CC ), 55.7 (C ), 58.5 (C2), 111.5 (C8), 114.4 (C5), 115.1 (C1), 116.2 (C7), 127.9 (C), 14.2 (C4), 16.6 (C9), 152.6 (C6), 166. (C), 174.6 (C). Anal. Calcd for C 15 17 5 : C, 61.85;, 5.88;, 4.81. Found: C, 61.62;, 6.1;, 5.6. MS m/z (EI) 291.2 (M +, 11%), 2. (26), 22.2 (1), 17.2 (7), 11.2 (6), 116.2 (4). Dimethyl 6,7-dimethoxy-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (d) C C 5 6 1 7 8 9 4 1 C 2 C Yellow oil; yield (62%); R f.16 (2:1 Cyclohexane/EtAc). IR (kapilar) 67 (), 1725 (C) cm -1. 1 -MR ( Mz, CDCl ): s,, C ),.72,.8,,82,.8 (s, 12, CC and 6,7-C ), 4.6 (bs, 1, ), 6.21 (s,1, Ar-), 6.57 (s, 1, Ar-), 7.54 (s, 1, -C=C). C-MR ( Mz, CDCl ): 26.9 (C ), 51.9, 52.6 (CC ), 55.6, 56.4 (C ), 58.5 (C2), 98.4 (C8), 18.6 (C5), 11.5 (C9), 127.4 (C), 1.6 (C4), 17.7 (C6), 1141.9 (C1), 15.5 (C7), 166.1 (C), 174.9 (C). Anal. Calcd for C 16 19 6 : C, 59.81;, 5.96;, 4.6. Found: C, 55.65;, 5.81;,.918. MS m/z (EI) 21.2 (M +, 14%), 26.2 (25), 262.2 (1), 246.1 (16), 218.2 (7), 2.2 (5), 11.1 (6). Dimethyl 5,8-dimethoxy-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (e) C 5 6 1 7 4 8 9 C 1 C 2 C Yellow solid; yield (45%); R f.2 (2:1 Cyclohexane/EtAc); m.p: 1-11 o C. IR (KBr) 81 (), 1727 (C) cm -1. 1 -MR ( Mz, CDCl ): s,, C ),.7,.71,,78, Page S
ARKIVC 212 (viii) S1-S.81 (s, 12, CC and 5,8-C ), 4.9 (bs, 1, ), 6. (s, 1, -C=C), 6.14-6.16 (d,1, J 8.8 z, Ar-), 6.65-6.67 (d, 1, J 8.8 z, Ar-). C-MR (4 Mz, CDCl ): 26.8 (C ), 52., 52.6 (CC ), 56.1, 56.2 (C ), 57.6 (C2), 99.6 (C1), 17.6 (C6), 111.4 (C7), 126.4 (C8), 129.2 (C), 14. (C4), 141.1 (C9), 149.8 (C5), 169.4 (C), 174.5 (C). Anal. Calcd for C 16 19 6 : C, 59.81;, 5.96;, 4.6. Found: C, 59.;, 5.61;, 4.26. MS m/z (EI) 21.1 (M +, 5%), 26.1 (16), 262.1 (1), 247.1 (6), 22.1 (), 22.1 (4), 17.1 (). Dimethyl 6- t Butyl -2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (f) 6 7 C 5 1 4 2 8 9 C 1 Yellow solid; yield (7%); R f.66 (2:1 Cyclohexane/EtAc); m.p: 14-141 o C. IR (KBr) 6 (), 174, 1718 (C) cm -1. 1 -MR (4Mz, CDCl ): s, 9, t Bu s,, C ),.7 (s,, CC ),.86 (s,, CC ), 4.4 (bs, 1, ), 6.56-6.58 (d, 1, J 8., Ar- ), 6.65 (bs, 1, -C=C), 7.11-7.1 (d, 1, J 8., Ar- ), 7.86 (br, 1, Ar- ). C- MR (4Mz, CDCl ): 27.6 (C ), 1., 1.2, 1. (-C(C ) ), 1.5 (-C(C ) ), 52., 52.7 (2xCC ), 58.5 (C2), 11.6 (C8), 12.4 (C1), 12.2 (C5), 126.6 (C7), 128. (C). 12.5 (C4), 14. (C6), 141.1 (C9), 166.1 (C), 174.5 (C). Anal. Calcd for C 18 2 4 : C, 68.12;, 7.;, 4.41. Found: C, 67.7;, 7.44;, 4.. MS m/z (EI) 17.2 (M +, 4%), 259.2 (18%), 258.2 (1), 24.2 (1), 242.2 (15), 228.1 (6), 199.1 (). Dimethyl 6-methoxy-2,8-dimethyl-1,2-dihydroquinoline-2,4-dicarboxylate (g) C 5 4 C 1 6 7 8 9 1 2 C Yellow solid; yield (77%); R f.5 (2:1 Cyclohexane/EtAc); m.p: 82-8 o C. IR (KBr) 82 (), 174, 1718 (C) cm -1. 1 -MR (4Mz, CDCl ): s,, C ), 2.2 (s,, C ),.7 (s,, CC ),.7 (s,, C ),.84 (s,, CC ), 6.6-6.64 (d, 1, J 2.6, Ar- ), 6.7 (br, 1, -C=C), 7.-7.4 (d, 1, J 2.6, Ar-). C-MR (4 Mz, CDCl ): C 27.2 (C ), 52., 52.8 (CC ), 55.7 (C ), 58.5 (C2), 19.(C5), 117. (C1), 117.9 (C7), 122.7 (C8), 128. (C). 1.6 (C4), 14.8 (C9), 151.7 (C6), 166. (C), 174.8 (C). Anal. Calcd for C 16 19 5 : C, 62.94;, 6.27;, 4.59. Found: C, 62.84;, 6.42;, 4.59. MS m/z (EI) 5.1 (M +, 6%), 247.2 (2), 246.1 (1), 2.1 (8), 187.1 (7), 145.1 (4). Page S4
ARKIVC 212 (viii) S1-S Dimethyl 6- phenyl-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (h) 4 5 6 2 1 6 C 5 1 4 7 8 9 1 2 C Yellow solid; yield (65%); R f.56 (2:1 Cyclohexane/EtAc); m.p: 19-11 o C. IR (KBr) 64 (), 1712 (C) cm -1. 1 -MR ( Mz, CDCl ): s,, C ),.76 (s,, CC ),.88 (s,, CC ), 4.58 (bs, 1, ), 6.69-6.72 (bs, 2, -C=C and Ar-), 7.2-7.1 (m, 1, Ar-), 7.1-7.4 (m,, Ar- ), 7.52-7.55 (m, 2, Ar- ), 8.1 (br, 1, Ar- ). C-MR (4 Mz, CDCl ): 27.7 (C ), 52.1, 52.9 (2xCC ), 58.7 (C2), 114.4 (C8), 116.5 (C1), 125.2 (C2 ), 126.1 (C7), 126.2 (C6 ). 126.4 (C4 ), 127. (C5), 128.2 (C), 128. (C5 ), 128.5 (C ), 11.5 (C6), 12.9 (C4), 141. (C1 ), 141.8 (C9), 165.9 (C), 174.2 (C). Anal. Calcd for C 2 19 4 : C, 71.2;, 5.68;, 4.15. Found: C, 7.99;, 5.77;, 4.11. MS m/z (EI) 7.2 (M +, 7%), 279.2 (21), 278.2 (1), 219.2 (7), 19.2 (4), 59. (2). Compound (i) 17b C 5 1 4 6 11 14 7 12 8 1 9 1 2 C Yellow solid; yield (5%); R f.56 (2:1 Cyclohexane/EtAc); m.p: 121-122 o C. IR (KBr) 96 (), 172 (C) cm -1. 1 -MR ( Mz, CDCl ): s,, C ),.77 (s,, CC ),.89 (s,, CC ), 5. (bs, 1, ); 6.5-6.6 (d, 1, J 8.5 z, Ar-), 6.68 (s, 1, C=C), 7.21-7.24 (d, 1, J 8.7 z, Ar-), 7.4-7.47 (m, 2, Ar-), 7.7-7.76 (m, 1, Ar- ), 7.8-7.87 (m, 1, Ar-), 7.87-7.89 (d, 1, J 8.7 z, Ar-). C-MR ( Mz, CDCl ): 27. (C ), 52., 52.9 (2xCC ), 58.6 (C2), 111.1 (C1), 117.8 (C6), 119.9 (C5), 122.2 (C12), 12.9 (C9). 125.2 (C8), 126.4 (C7), 128.5 (C), 129. (C), 1.2 (C11), 14.2 (C4), 17.9 (C14), 166.5 (C), 174.4 (C). Anal. Calcd for C 18 17 4 : C, 69.44;, 5.5;, 4.5. Found: C, 69.4;, 5.55;, 4.47. MS m/z (EI) 11.1 (M +, 16%), 25.2 (5), 252.1 (1), 192.1 (21), 59. (2). Compound (j) Page S5
ARKIVC 212 (viii) S1-S Yellow solid; yield (67%); R f.4 (2:1 Cyclohexane/EtAc); m.p: 17-175 o C. IR (KBr) 51 (), 1716 (C) cm -1. 1 -MR (4 Mz, CDCl ): s,, C ),.7 (s,, CC ),.8 (s,, CC ), 6.44 (s, 1, -C=C), 6.96-6.99 (d, 1, J 8.7 z, Ar-), 7.21-7.25 (m, 1, Ar-), 7.-7.4 (m, 2, Ar-), 7.6-7.69 (m, 2, Ar-). C-MR (4Mz, CDCl ): 25.5 (C ), 52., 52.8 (2xCC ), 57.8 (C2), 11.4 (C1), 117. (C7), 122.4 (C5), 12.4 (C9), 126.1 (C8). 127.1 (C12), 128.6 (C1), 129.5 (C6), 129.9 (C), 1. (C14), 1.9 (C4), 142. (C11), 169.4 (C), 174. (C). Anal. Calcd for C 18 17 4 : C, 69.44;, 5.5;, 4.5. Found: C, 69.52;, 5.7;, 4.45; MS m/z (EI) 11.1 (M +, 5%), 25.1 (19), 252.1 (1), 19.1 (1), 118.6 (4), 59. (). Dimethyl 2,6,8-trimethyl -1,2-dihydroquinoline-2,4-dicarboxylate (k) 5 6 7 8 C 1 4 9 1 2 C Pale yellow crystalline solid; yield (6%); R f.25 (2:1 Cyclohexane/EtAc); m.p: 147-148 o C. IR (KBr) 52 (), 174, 179 (C) cm -1. 1 -MR (4 Mz, CDCl ): s,, C ), 2.1, 2.2 (s, 6, 2xC ),.7,.8 (s, 6, 2xCC ), 6. (s, 1, Ar-), 6.42 (bs, 2, Ar- and -C=C). C-MR (4 Mz, CDCl ): XC 26.9 (C ), 52.2, 52.7 (CC ), 57.7, (C2), 11.5(C1), 12. (C8), 1.4, 1.9 (C5 and C6), 14.7 (C7), 19.4 (C4), 14.4 (C9), 169. (C), 174. (C). Anal. Calcd for C 16 19 4 : C, 66.42;, 6.62;, 4.84. Found: C, 66.41;, 6.69;, 4.86. MS m/z (EI) 289.1 (M +, 5%), 21.2 (28), 2.1 (1), 198.1 (8), 171.1 (15), 17.1 (9), 128.1 (6). Dimethyl 6- acetyl-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (I) 6 7 C 5 1 4 8 9 2 C 1 Yellow crystalline solid; yield (91%); R f.1 (2:1 Cyclohexane/EtAc); m.p: 152-15 o C. IR (KBr) 29 (), 1742, 1664 (C) cm -1. 1 -MR (4 Mz, CDCl ): s,, C ), s,, CC ),.74 (s,, CC ),.86 (s,, CC ), 5. (br, 1, ); 6.5-6.6 (d, 1, J 8.5 z, Ar- ), 6.69 (br, 1, C=C), 7.71-7.74 (dd, 1, J 8.5 and 2. z, Ar- ), 8.49-8.5 (d, 1, J 2. z, Ar- ). C-MR (4 Mz, CDCl ): 26.1 (C ), 28.2 (CC ), 52.2, 5. (2xCC ), 58.9 (C2), 11.5 (C8), 114.5 (C1), 127. (C6), 127.8 (C5), 128.1 (C). 1. (C7), 12.4 (C4), 146.5 (C9), 165.5 (C), 17. (C), 196. (C). Anal. Calcd for Page S6
ARKIVC 212 (viii) S1-S C 16 17 5 : C, 6.6;, 5.65;, 4.62. Found: C, 6.42;, 5.7;, 4.6. MS m/z (EI).2 (M +, %), 245.2 (14), 244.2 (1), 21.2 (7), 186.2 (4), 114.9 (), 59.4 (1). Dimethyl 6- cyano-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (m) C 6 5 1 C 4 7 8 9 1 2 C White solid; yield (71%); R f.2 (2:1 Cyclohexane/EtAc); m.p: 14-141 o C. IR (KBr) 51 (), 1724, 1718 (C) cm -1. 1 -MR (4Mz, CDCl ): s,, C ),.78 (s,, CC ),.87 (s,, CC ), 4.9 (br, 1, ), 6.58-6.6 (d, 1, J 8. z, Ar- ), 6.75 (br, 1, -C=C), 7.-7. (dd, 1, J 8. and 1.8 z, Ar- ), 8.19-8.2 (d, 1, J 1.8, Ar- ). C-MR (4 Mz, CDCl ): 28.4 (C ), 52.4, 5.2 (2xCC ), 58.9 (C2), 1.7 (C6), 114. (C8), 115.6 (C1), 119.9 (C), 126.4 (C7). 11. (C), 1.4 (C4), 1.5 (C5), 145.6 (C9), 165. (C), 17.1 (C). Anal. Calcd for C 15 14 2 4 : C, 62.9;, 4.9;, 9.79. Found: C, 62.96;, 4.82;, 9.81. MS m/z (EI) 86.1 (M +, 1%), 228.1 (15%), 227.1 (1), 199.1 (5), 168. (2), 167.1 (6), 14.1 (6), 59.2 ( 4). Dimethyl 6-nitro-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (n) 17 C 2 7 6 5 1 8 9 4 1 2 C Yellow solid; yield (97%); R f.2 (2:1 Cyclohexane/EtAc); m.p: 15-16 o C. IR (KBr) 47 (), 1721 (C) cm -1. 1 -MR (Mz, CDCl ): s,, C ),.8 (s,, CC ),.9 (s,, CC ), 5.22 (bs, 1, ), 6.5-6.6 (d, 1, J 8.9 z, Ar-), 6.78 (d, 1, J 1.54 z, C=C), 7.9-8. (dd, 1, J 8.9 and 2.5 z, Ar-), 8.8-8.84 (d, 1, J 2.5, Ar-). C-MR (4 Mz, CDCl ): 28.6 (C ), 52.5, 5. (2xCC ), 59. (C2), 11. (C8), 114.4 (C1), 12.4 (C5), 126.2 (C7), 126.4 (C). 1. (C4), 19.1 (C6), 147.6 (C9), 164.9 (C), 172.7 (C). Anal. Calcd for C 14 14 2 6 : C, 54.9;, 4.61;, 9.15. Found: C, 54.84;, 4.45;, 9.15. MS m/z (EI) 6.1 (M +, 1%), 248.1 (15), 247.1 (1), 21.1 (47), 186.1 (12), 142.1 (9), 59. ( 5). Page S7
ARKIVC 212 (viii) S1-S Dimethyl 2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (o) 17 6 7 5 14 C 8 9 1 2 C Yellow solid; yield (6%); R f.5 (2:1 Cyclohexane/EtAc); m.p: 7 o C. IR (KBr) 65 (), 171 (C) cm -1. 1 -MR (4 Mz, CDCl ): s,, C ),.7 (s,, CMe),.8 (s,, CMe), 4.5 (bs, 1, ), 6.61-6.6 (m,1, Ar-), 6.66 (s, 1, -C=C), 6.71-6.74 (m, 1, Ar-), 7.-7.1 (m, 1, Ar-), 7.77-7.79 (m, 1, Ar-). C-MR (4 Mz, CDCl ): 27.6 (C ), 52., 52.8 (CC ), 58.5 (C2), 114.1 (C5), 116. (C8), 118.6 (C6), 126.4 (C1), 128.1 (C7), 129.6 (C), 12.5 (C4), 142.4 (C9), 166. (C), 174.2 (C). Anal. Calcd for C 14 15 4 : C, 64.6;, 5.79;, 5.6. Found: C, 64.4;, 5.81;, 5.41. MS m/z (EI) 261.1 (M +, %), 2.1 (15), 22.1 (1), 188.1 (4), 174.1 (5), 14.1 (18), 142.1 (7), 115.1 (7), 59.1(5). Dimethyl 5,6,7-trimethoxy-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (p) C Me 6 5 Me 1 4 2 7 9 C Me 8 1 White crystalline solid; yield (8%); R f.16 (2:1 Cyclohexane/EtAc); m.p: 12-121 o C. IR (KBr) 59 (), 179 (C) cm -1. 1 -MR ( Mz, CDCl ): s,, C ),.69,.71,,79,.8 (s, 15, CC and 5,6,7-C ), 4.42 (bs, 1, ), 5.85 (bs, 1, Ar- ), 5.99 (s, 1, -C=C). C-MR ( Mz, CDCl ): 26.9 (C ), 52.1, 52.6 (CC ), 55.7, 58. (2xC ), 58.(C2), 6.9 (C ), 9.7 (C8), 14. (C1), 12.8 (C), 129. (C4), 14.2 (C9), 19.7 (C5), 149.8 (C6), 155.1 (C7), 17. (C), 174.9 (C). Anal. Calcd for C 17 21 7 : C, 58.11;, 6.2;,.99. Found: C, 57.7;, 5.91;,.9. MS m/z (EI) 51.2 (M +, 7%), 29.1 (19), 292.2 (1), 262.1 (6), 217.1 (7), 1.1 (). Dimethyl 6-bromo-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (q) Br 6 7 5 C 1 4 8 9 1 2 C Yellow crystalline solid; yield (81%); R f.5 (2:1 Cyclohexane/EtAc); m.p: 16-17 o C. Page S8
ARKIVC 212 (viii) S1-S IR (KBr) 52 (), 1724 (C) cm -1. 1 -MR (4Mz, CDCl ): s,, C ),.74 (s,, CC ),.85 (s,, CC ), 4.51 (bs, 1, ), 6.4-6.5 (d, 1, J 8.5 z, Ar-), 6.71 (bs, 1, -C=C), 7.14-7.17 (dd, 1, J 8.5 and 2.1 z, Ar- ), 7.97-7.98 (d, 1, J 2.1, Ar- ). C-MR (4 Mz, CDCl ): 27.5 (C ), 52.4, 52.9 (2xCC ), 58.6 (C2), 11.4 (C6), 115.6 (C8), 117.9 (C9), 127. (C7), 129. (C). 12.1 (C5), 1.8 (C4), 141.4 (C9), 165.4 (C), 17.9 (C). Anal. Calcd for C 14 14 Br 4 : C, 49.4;, 4.15;, 4.12. Found: C, 49.8;, 4.1;, 4.1. MS m/z (EI) 9. (M +, 5%), 28. (12%), 282. (97), 28. (1%), 221. (7), 21.1 (11), 142.1 (6), 115.1 ( 6), 59.2 (6). Dimethyl 6-iodo-2-methyl-1,2-dihydroquinoline-2,4-dicarboxylate (r) C I 7 6 5 1 4 2 8 9 1 C Yellow crystalline solid; yield (4%); R f.56 (2:1 Cyclohexane/EtAc); m.p: 12 o C. IR (KBr) 5 (), 172 (C) cm -1. 1 -MR (4 Mz, CDCl ): s,, C ),.74 (s,, CC ),.86 (s,, CC ), 4.51 (bs, 1, ), 6.-6.4 (d, 1, J 8.4 z, Ar- ), 6.68-6.69 (d, 1, J 2. z, -C=C), 7.2-7.5 (dd, 1, J 8.4 and 2. z, Ar- ), 8.1-8.14 (d, 1, J 2., Ar-). C-MR (4 Mz, CDCl ): 27.6 (C ), 52.24, 52.97 (2xCC ), 58.5 (C2), 116.15 (C8), 118.4 (C1), 126.9 (C), 1.5 (C4), 14.8 (C5). 18. (C7), 142. (C9), 165.4 (C), 17.9 (C). Anal. Calcd for C 14 14 I 4 : C, 4.4;,.64;,.62. Found: C, 4.81;,.58;,.56. MS m/z (EI) 87.1 (M +, 7%), 29. (11), 28. (1), 21.2 (2), 142.2 (4), 59. (2). Dimethyl 6-acetyl-4-hydroxy-2-methyl-1,2,,4-tetrahydroquinoline-2,4-dicarboxylate (4) White solid; yield (54%); R f.5 (1:1 Cyclohexane/EtAc); m.p: 2-21 o C. IR (KBr) 25 (), 174 (C) cm -1. 1 -MR (Mz, MeD): s,, C ), 2.27.2.64 (AB, 2, J AB 1.7 z, -C 2 ), 2.4 (s,, CC ),.6 (s,, CC ),.77 (s,, CC ), 6.71-6.7 (d, 1, J 8.4 z, Ar- ), 7.59-7.6 (d, 1, J 2. z, Ar- ), 7.72-7.75 (dd, 1, J 8.6 and 2. z, Ar- ). MS m/z (EI) 21.2 (M +, 21%), 26.2 (5), 262.2 (28), 245.2 (2), 244.2 (1), 22.2 (29). 16.2 (7), 1.2 (4), 59.2 (4). RMS-EI calcd. for C 16 19 6 [M+]: 21.1269; Found: 21.12115. Page S9
ARKIVC 212 (viii) S1-S Lactone (9) MW (1 bar, 15 watt, 1 o C, 7 h). Pale purple solid; yield (2%); R f.4 (1:1 Cyclohexane/EtAc); m.p: 98-99 o C. 1 -MR (Mz, CDCl ): s,, C ),.8 (s,, Me), 6.4 (s, 1, =C), 6.94 (1, br, ), 7.27-7. (1, dd, J 5. and 8., Ar-), 7.5-7.52 (1, dd, J 1. and 8. z, Ar-), 8.-8.4 (1, dd, J 1.4 and 4.6 z, Ar-). C- MR (4 Mz, CDCl ): 2.1 (C ), 5.4 (C ), 84.81 (C2), 115.17 (C), 122.8 (C5 ), 12.2 (C4 ), 128. (C6 ), 1.9 (C2 ), 19.9 (C ), 141,6 (C4), 168.8 (C), 169.4 (C). Crystal data for 9: C 12 11 Cl 2 4, M = 282.68, crystallizes as colourless blocks, crystal dimensions.5 x. x.2 mm. Monoclinic, a = 7.575(1) Å, b = 14.47(2) Å, c = 11.6615(14) Å, β = 96.641(1), V = 126.9() Å, z = 4, D c = 1.486 Mgm -, space group P2 1 /c (o. 14), MoK α radiation (λ =.717), μ =.14 mm -1, F() = 584. The X-ray data were collected at 29(2) K in the range 4.5 < 2θ < 56 on a icolet P/F diffractometer by the Wyckoff scan method. The 44 unique reflections were corrected for Lorentzian polarization effects, but not for absorption. Intensity of 1647 reflections were larger than 2σ(I). The structure was solved by Direct Methods and refined by full matrix least squares methods of F 2 with SELXTL-97 program package. ydrogen atoms were included in calculated positions and refined in riding mode. Refinement converged at a final R =.85 (wr 2 =.1548, I>2σ(I), 179 parameters, mean and maximum δ/σ. and.), with allowance of anisotropic displacement parameters for all non-hydrogen atoms. Minimum and maximum final rest-electron density is.255 and.26 eå -. Page S1
ARKIVC 212 (viii) S1-S 1 MR and 1 C MR Spectra of Compounds a-r and 4, 9 9.674 7.657 7.689 7.97 8. 6.645 6.665 6.592.762.858 2.59 1.62 25 2 15 1 5.5.7.7.8.6.2.2.24.24 9. 8. 7. 6. 5. 4.. 2. 1. 2.495 172.985 165.779 146.7 11.844 12.88 12.775 127.45 117.65 116.776 115.155 58.67 52.995 52.211 28.1 28.712 25 2 15 1 5 2 15 1 5 Figure S1. MR Spectrum of compound a. Page S11
ARKIVC 212 (viii) S1-S 7.616 7.294 7.254 7.24 6.985 6.926 6.945 6.84 6.79 6.86 6.611 6.62 4.496.812.761 1.576 6 5 4 2 1.21.67.26.55.29.22.25.24 1..98 1. 7. 6. 5. 4.. 2. 25 174.298 165.669 158.65 148.29 18.98 1.77 129.42 121.68 121.979 117.124 118.658 114.955 Ph 58.79 52.882 52.17 27.46 2 15 1 5 15 1 5 Figure S2. MR Spectrum of compound b. Page S12
ARKIVC 212 (viii) S1-S 7.488 7.498 6.694 6.7 6.72 6.741 6.599 6.57 4.48.854.746.721 Me 1.59 4 2 1.29.6.27.1.26.95.98.97.96 7. 6. 5. 4.. 2. 7 174.645 165.986 152.62 16.657 14.216 127.911 117.4 116.266 111.576 115.16 58.585 52.77 55.745 52.9 26.927 6 5 4 2 1 15 1 5 Figure S. MR Spectrum of compound c. Page S1
ARKIVC 212 (viii) S1-S 7.54 6.574 6.214 4.6.722.87.827.87 1.529 2 15 1 5.5.4.5.4.49.15.15 7. 6. 5. 4.. 2. 1. 174.965 166.172 15.52 141.97 17.727 127.451 1.64 18.622 11.546 98.486 56.42 58.551 55.684 52.689 51.97 29.645 26.99 5 15 1 Figure S4. MR Spectrum of compound d. 5 Page S14
ARKIVC 212 (viii) S1-S 7 1.54.71.75.788.81 6.24 6.142 6.164 6.652 6.674 6 5 4 2 1.1.1.28 1.1.97 1.97 1. -1 7. 6. 5. 4.. 2. 174.51 169.465 149.882 141.17 14.45 129.292 126.4 111.442 17.6 99.66 76.59 77.14 77.48 57.699 52.8 52.642 56.124 56.255 26.85 6 5 4 2 1 15 1 Figure S5. MR Spectrum of compound e. 5 Page S15
ARKIVC 212 (viii) S1-S C 6 1.27 1.545.76.866 4.4 4.42 6.561 6.581 6.659 7.114 7.14 7.86 C C 5 4 2 1.8.8.7.8.7.4..4 1. 8. 7. 6. 5. 4.. 2. 1. 174.548 166.129 141.177 12.546 14.1 128.21 126.647 12.274 12.476 11.664 115.871 58.579 52.779 52.1 1.1 1.212 1.87 1.57 27.687 2 15 1 5 15 1 ppm (f1) Figure S6. MR Spectrum of compound f. 5 Page S16
ARKIVC 212 (viii) S1-S C 7.7 7.44 6.6 6.69 6.79 C.846.78 2.21 1.571 4 C C C 2 1.9.8.1.7.66..2 7. 6. 5. 4.. 2. 4 174.815 166.67 151.781 14.879 128.74 1.65 122.75 117.96 117.7 19.57 58.576 55.71 52.84 52.78 27.4 27.288 17.19 2 1 15 1 ppm (f1) Figure S7. MR Spectrum of compound g. 5 Page S17
ARKIVC 212 (viii) S1-S 1.592.765.88 4.582 6.692 6.72 7.45 7.48 7.528 7.529 7.554 8.17 25 2 15 1 5.27.59 1..5.2.99.97.99 8. 7. 6. 5. 4.. 2. 174.24 165.945 141.896 141.49 12.92 128.67 128.7 128.56 11.581 127.15 126.159 126.254 126.42 125.215 114.471 116.527 58.724 52.915 52.161 27.7 7 6 5 4 2 1 15 1 5 Figure S8. MR Spectrum of compound h. Page S18
ARKIVC 212 (viii) S1-S C 7.871 7.89 7.767 7.88 7.75 7.471 7.48 7.217 7.245 6.686 C C.896.777 1.628 4 2 1.2.2..59.29.27.96.98.99 8. 7. 6. 5. 4.. 2. 174.47 166.515 14.27 17.9 1.245 126.441 128.592 129.85 125.21 122.214 12.994 119.986 111.1 117.814 C C C 58.659 52.92 52.87 27.88 1 5 15 1 Figure S9. MR Spectrum of compound i. 5 Page S19
ARKIVC 212 (viii) S1-S 1.565.72.8 6.44 6.969 6.99 7.215 7.255 7.2 7.41 7.68 7.659 7.67 7.692 1 5.2.6.65.2.2.29 1. 1. 1. 8. 7. 6. 5. 4.. 2. 174.8 169.478 129.5 129.974 1.5 1.925 142.1 128.61 127.125 126.178 12.185 122.468 11.489 117.4 57.882 52.1 52.88 25.564 2 15 1 5 15 1 5 Figure S1. MR Spectrum of compound j. Page S2
ARKIVC 212 (viii) S1-S 7.248 6.1 6.429.81.74 2.22 2.17 1.59 5 4 2 1.62.28.99.99.98.99 1. 7. 6. 5. 4.. 2. 174.59 169.5 14.446 19.429 14.75 1.482 1.97 12.48 11.557 57.776 52.25 52.776 26. 21.87 2.58 4 2 1 ppm (f1) 15 1 5 Figure S11. MR Spectrum of compound k. Page S21
ARKIVC 212 (viii) S1-S 8.491 8.496 7.717 7.74 6.589 6.61 6.691 5.78.867.747 2.491 1.57 6 5 4 2 1....2.27.98.97.98 1. 8. 7. 6. 5. 4.. 2. 1. 5 196.94 17.59 165.5 146.582 127.14 127.81 128.158 1.67 12.489 114.5 11.571 58.986 5.86 52.285 26.189 28.258 4 2 1 2 15 1 5 Figure S12. MR Spectrum of compound l. Page S22
ARKIVC 212 (viii) S1-S 7 C 8.197 8.22 7.5 7.9 7.26 7. 6.586 6.67 6.758 4.917.879.78 C 1.591 6 C C 5 4 2 1.26..28.29.25 1..97 1. -1 8. 7. 6. 5. 4.. 2. 17.16 165.6 145.69 1.42 1.527 126.426 11.5 119.929 114.91 115.628 1.77 C 58.941 5.226 52.45 28.429 2 15 1 5 15 1 5 Figure S1. MR Spectrum of compound m. Page S2
ARKIVC 212 (viii) S1-S 8.82 8.841 7.984 7.992 8.1 8.22 6.799 6.57 6.6 5.128.85.99 2 1.621 25 2 15 1 5.26..29.1.25.99.99.99 9. ppm (f1) 8. 7. 6. 5. 4.. 2. 172.786 164.95 147.659 19.18 126.57 126.28 126.47 1.76 12.417 114.44 11.19 11.18 2 59.22 5.7 52.521 28.626 5 25 2 15 1 5 15 1 Figure S14. MR Spectrum of compound n. 5 Page S24
ARKIVC 212 (viii) S1-S C 1 1.558.742.859 4.5 6.615 6.64 6.71 6.748 7.65 7.1 7.772 7.795 C C 5 1. 1.5 1.1 1. 1.1.97.4.4.5 8. 7. 6. 5. 4.. 2. 6 174.299 166.18 142.448 12.595 129.624 118.64 126.47 128.169 116.5 114.155 C C C 58.569 52.851 52.96 27.629 5 4 2 1 15 1 Figure S15. MR Spectrum of compound o. 5 Page S25
ARKIVC 212 (viii) S1-S 5.99 5.857 4.429.71.81 1.482 2 15 1 5..25.25 2.81 1.84 1. 7. 6. 5. 4.. 2. 1. 174.947 17.78 155.158 149.81 19.788 14.2 129.97 12.825 14.5 9.772 6.84 6.94 58.1 52.114 52.692 55.792 26.96 6 5 4 2 1 15 1 5 Figure S16. MR Spectrum of compound p. Page S26
ARKIVC 212 (viii) S1-S 8 7.979 7.986 7.145 7.172 6.716 6.496 6.517 4.51.858.74 Br 1.548 7 6 5 4 2 1.25.28.28..95.95.96-1 8. 7. 6. 5. 4.. 2. 1. 17.91 165.419 141.45 127.5 129.86 12.161 1.864 117.955 11.485 115.614 Br 58.619 52.964 52.247 27.546 2 1 15 1 Figure S17. MR Spectrum of compound q. 5 Page S27
ARKIVC 212 (viii) S1-S 8.1 8.18 7.26 7.1 7.47 7.52 6.98 6.419 6.687 6.692 4.514.86.748 I C 1.549 7 C C 6 5 4 2 1.25.28.28.29.28.96.92 1. -1 8. 7. 6. 5. 4.. 2. 7 17.912 165.422 142.46 14.822 18.4 126.955 1.55 118.479 116.152 79.84 58.561 52.975 52.245 27.66 6 I 5 4 2 1 15 1 Figure S18. MR Spectrum of compound r. 5 Page S28
ARKIVC 212 (viii) S1-S 7.75 7.72 7.597 7.62 6.718 6.79.77.618 2.648 2.614 2.45 2.1 2.279 1.527 7 6 5 4 2 1.2.25.26 1.1 1..28 1..26 1. -1 ppm (f1) 7. 6. 5. 4.. 2. Figure S19. MR Spectrum of compound 4. Page S29
168.825 169.415 1.987 19.94 141.671 122.85 12.21 128.19 115.171 76.749 77.68 77.85 84.819 5.4 2.152 1. 1.1.24.2.6 1.4.97.1 4.8 6.49 6.949 7.271 7.284 7.291 7. 7.5 7.5 7.52 7.524 8. 8.6 8.44 8.48.8 1.797 General Papers ARKIVC 212 (viii) S1-S C C Cl 1 9 8 7 6 5 4 2 1 ppm C C Cl 19 18 17 16 15 14 1 12 11 1 9 8 7 6 5 4 2 1 ppm Figure S2. MR Spectrum of compound 9. Page S