Supporting Information Synthesis of Pyrrole-Fused C,N-Cyclic Azomethine Imines and Pyrazolopyrrolopyrazines: Analysis of Their Aromaticity Using Nucleus-Independent Chemical Shifts Values Merve Sinem Özer, Nurettin Menges,, Selbi Keskin,,ǁ Ertan Şahin, Metin Balci *, Department of Chemistry, Middle East Technical University, 06800 Ankara, Turkey Faculty of Pharmacy, Yüzüncü Yil University, 65100 Van, Turkey Department of Chemistry, Atatürk University, 25240, Erzurum, Turkey ǁ Department of Chemistry, Giresun University, 28100 Giresun, Turkey Table of Content Page 1. Experimental Section S2 2. General Procedure for compound 12a-h S2 3. General Procedure for compound 13a-h S5 4. General Procedure for compound 14-17 S7 5. NMR Spectra S10 6. Theoretical Calculations S33 7. Methodology S33 8. Theoretical Coordinates for compound 13a,c,d,f, 14-17 and 23-25 S33 9. X-Ray structure determination of 13d S40 10. References S42 S1
Experimental Section General Methods. NMR spectra were recorded on a 400 MHz spectrometer. Infrared (IR) spectra were recorded in the range 4000-600 cm -1 via ATR diamond. Melting points were determined using a melting point apparatus and were uncorrected. Mass spectra were recorded by LC-MS TOF electrospray ionization technique. Column chromatography was performed on silica gel (60-mesh), TLC was carried out on 0.2 mm silica gel 60 F 254 analytical aluminum plates. Evaporation of solvents was performed at reduced pressure, using a rotary vacuum evaporator. General Procedure for compound 12a-h. Pyrrole aldehyde 9 or 10 (1 equiv.) and hydrazide 11a-e (1 equiv) were stirred in 5 ml EtOH at room temperature for 24 h. Evaporation of the solvent gave the corresponding products 12a-h. N'-((1-(Prop-2-yn-1-yl)-1H-pyrrol-2-yl)methylene)formohydrazide (12a): Pyrrole aldehyde 9 (0.50 g, 3.76 mmol) and formohydrazide (0.23 g, 3.76 mmol) were reacted as described above. After evaporation of the solvent the residue was crystallized from CHCl 3 in petroleum ether atmosphere to give the product 12a as brown crystals (0.66 g, 100%, NMR yield), mp. 124-126 C. 1 H NMR (400 MHz, CDCl 3 ) δ 9.75 (bd, J = 8.8 Hz, 1H), 8.71 (d, J = 10.3 Hz, 1H), 7.79 (s, 1H), 7.04 (dd, J = 2.3, 1.8 Hz, 1H), 6.49 (dd, J = 3.8, 1.7 Hz, 1H), 6.21 (dd, J = 3.7, 2.8 Hz, 1H), 5.13 (d, J = 2.5 Hz, 2H), 2.42 (t, J = 2.5 Hz, 1H); 13 C NMR (101 MHz, CDCl 3 ) δ 179.8, 165.2, 139.3, 127.0, 117.8, 109.5, 78.4, 73.9, 38.8; IR (ATR, cm -1 ) 3186, 1676, 1473, 1396, 1362, 1276, 1069, 1021, 776, 710, 650; HRMS for C 9 H 10 N 3 O [M+H] + : 176.08184. Found: 176.08308. (E/Z)-N'-((1-(Prop-2-yn-1-yl)-1H-pyrrol-2-yl)methylene)acetohydrazide (12b). Pyrrole aldehyde 9 (0.53 g, 4.00 mmol) and acetohydrazide (0.30 g, 4.00 mmol) were reacted as described above. After evaporation of the solvent the residue was crystallized from ethanol to give the product 12b as white sponge crystals (0.76 g, 100%, crude yield). According to NMR calculation, E-isomer 74%, Z-isomer is 26%. E-isomer; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.97 (s, 1H), 7.89 (s, 1H), 7.05 (dd, J = 2.4, 2.0 Hz, 1H), 6.43 (dd, J = 3.7, 1.7 Hz, 1H), 6.11 (dd, J = 3.6, 2.8 Hz, 1H), 5.10 (d, J = 2.4 Hz, 2H), 3.35 (t, J = 2.4 Hz, 1H), 2.16 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 171.6, 135.5, 126.8, 126.5, 115.3, 108.7, 79.9, 75.2, 38.0, 20.4. Z-isomer; 1 H NMR (400 MHz, DMSO-d 6 ) S2
δ 11.11 (s, 1H), 8.08 (s, 1H), 7.06 (dd, J = 2.5, 1.8 Hz, 1H), 6.48 (dd, J = 3.7, 1.7 Hz, 1H), 6.14 (dd, J = 3.6, 2.8 Hz, 1H), 5.20 (d, J = 2.5 Hz, 2H), 3.40 (t, J = 2.5 Hz, 1H), 1.91 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 165.0, 138.5, 126.5, 126.4, 114.7, 109.1, 79.7, 75.7, 37.1, 21.6.; IR (ATR, cm -1 ) 3248, 1675, 1427, 1390, 1348, 1125, 1031, 885, 726, 669, 548; HRMS for C 10 H 12 N 3 O [M+H] + : 190.09749. Found: 190.09957. N -((1-(Prop-2-yn-1-yl)-1H-pyrrol-2-yl)methylene)benzohydrazide (12c). Pyrrole aldehyde 9 (0.50 g, 3.76 mmol) and benzoyl hydrazide (0.51 g, 3.76 mmol) were reacted as described above. After evaporation of the solvent the residue was crystallized from CHCl 3 in petroleum ether atmosphere to give the product 12c as white crystals (0.55 g, 58%), mp. 120 122 C. 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.62 (s, 1H), 8.40 (s, 1H), 7.90 (dd, J = 7.1, 1.2 Hz, 2H), 7.58 (t, J = 7.2 Hz, 1H), 7.52 (t, J = 7.3 Hz, 2H), 7.12 (d, J = 1.8 Hz, 1H), 6.55 (dd, J = 3.6, 1.5 Hz, 1H), 6.18 (dd, J = 3.4, 3.0 Hz, 1H), 5.28 (d, J = 2.3 Hz, 2H), 3.43 (t, J = 2.3 Hz, 1H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 162.6, 140.5, 133.6, 131.5, 128.4, 127.4, 126.7, 126.6, 115.1, 109.2, 79.7, 75.7, 37.1; IR (ATR, cm -1 ) 3289, 1646, 1602, 1559, 1397, 1279, 1124, 1060, 718, 685, 632; HRMS for C 15 H 14 N 3 O [M+H] + : 252.11314. Found: 252.11529. 4-Methyl-N'-((1-(prop-2-yn-1-yl)-1H-pyrrol-2-yl)methylene)benzenesulfonohydrazide N O N S NH O (12d). Pyrrole aldehyde 9 (0.13 g, mmol) and p- toluenesulfonyl hydrazide (0.19 g, mmol) were reacted as described above. After evaporation of the solvent the residue was crystallized from CHCl 3 in petroleum ether atmosphere to give the product 12d as brownish crystals in quantitative yield (0.30 g, 100%, NMR yield), mp. 110-112 C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.16 (s, 1H), 7.86 (d, J = 8.3 Hz, 2H), 7.72 (s, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.02 (dd, J = 2.3 1.9 Hz, 1H), 6.38 (dd, J = 3.8, 1.7 Hz, 1H), 6.14 (dd, J = 3.8, 2.8 Hz, 1H), 4.99 (d, J = 2.5 Hz, 2H), 2.40 (s, 3H), 2.37 (t, J = 2.6 Hz, 1H); 13 C NMR (101 MHz, CDCl 3 ) δ 144.3, 142.2, 135.3, 129.8, 128.2, 127.1, 125.7, 118.0, 109.4, 78.4, 73.9, 38.6, 21.7; IR (ATR, cm -1 ) 3248, 1540, 1395, 1355, 1308, 1161, 1020, 930, 804, 736, 659, 547, 526; HRMS for C 15 H 16 N 3 O 2 S [M+H] + : 302.09577. Found: 302.09678. (E/Z)-N'-((1-(prop-2-yn-1-yl)-1H-pyrrol-2-yl)methylene)thiophene-2-carbohydrazide N O N C NH S (12e). Pyrrole aldehyde 9 (0.27 g, 2.00 mmol) and thiophene-2- S3
carbohydrazide (0.28 g, 2.00 mmol) were reacted as described above. After evaporation of the solvent, the residue was crystallized from MeOH to give the product 12e as pale yellow needles and sponge crystals in quantitative yield (0.51 g, 100%, NMR yield). E-isomer 63%; Z-isomer 37%. E-isomer; 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.66 (s, 1H), 8.36 (s, 1H), 7.87 (d, J = 3.2 Hz, 1H), 7.85 (d, J = 4.9 Hz, 1H), 7.23 7.17 (m, 1H), 7.11 (s, 1H), 6.56 (s, 1H), 6.18 (t, J = 3.0 Hz, 1H), 5.25 (s, 2H), 3.44 (s, 1H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 160. 9, 138.5, 136.7, 134.1, 134.0, 133.8, 126.4, 114.4, 109.2, 79.5, 76.2, 37.0; Z-isomer; 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.55 (s, 1H), 8.12 (s, 1H), 8.03 (s, 1H), 7.90 (d, J = 9.4 Hz, 1H), 7.24 7.17 (m, 1H), 7.11 (s, 1H), 6.64 (s, 1H), 6.18 (t, J = 3.0 Hz, 1H), 5.15 (s, 2H), 3.48 (s, 1H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 157.3, 140.3, 131.5, 128.5, 128.0, 126.8, 126.6, 115.2, 109.2, 79.7, 75.8, 37.2; IR (ATR, cm -1 ) 3225, 1624, 1558, 1520, 1416, 1328, 1299, 1132, 844, 804, 707; HRMS for C 13 H 12 N 3 OS [M+H] + : 258.06956. Found: 258.07130. N'-((1-(3-phenylprop-2-yn-1-yl)-1H-pyrrol-2-yl)methylene)benzohydrazide (12f). Pyrrole aldehyde 10 (209 mg, mmol) and benzoylhydrazine (136 mg, mmol) were reacted as described above. After evaporation of the solvent, the residue was crystallized from MeOH to give the product 12f as white crystals (298 mg, 91%), mp. 148-150 C. 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.68 (s, 1H), 8.47 (s, 1H), 7.92 (dd, J = 7.0, 1.4 Hz, 2H), 7.58 (t, J = 7.2 Hz, 1H), 7.52 (t, J = 7.2 Hz, 1H), 7.46 (dd, J = 7.2, 2.3 Hz, 2H), 7.37 (d, J = 1.6 Hz, 2H), 7.36 (d, J = 1.5 Hz, 2H), 7.23 (d, J = 1.8 Hz, 1H), 6.59 (dd, J = 3.6, 1.5 Hz, 1H), 6.21 (dd, J = 3.4, 2.9 Hz, 1H), 5.55 (s, 2H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 162.7, 140.7, 133.6, 131.5, 128.8, 128.6, 128.4, 127.5, 126.8, 126.7, 121.8, 115.2, 109.2, 85.4, 84.2, 48.6, 37.9; IR (ATR, cm -1 ) 3212, 3053, 1644, 1614, 1543, 1464, 1346, 1289, 1077, 720, 693; HRMS for C 21 H 18 N 3 O [M+H] + : 328.14444. Found: 328.14831. N'-((1-(3-phenylprop-2-yn-1-yl)-1H-pyrrol-2-yl)methylene)thiophene-2-carbohydrazide (12g). Pyrrole aldehyde 10 (209 mg, mmol) and thiophene-2- carbohydrazide (142 mg, mmol) were reacted as described above. After evaporation of the solvent the residue was crystallized from MeOH to give the product 12g as pale yellow crystals (303 mg, 91%, crude yield), mp. 121 123 C. 1 H NMR (400 MHz, CDCl 3 ) δ 1 (s, 1H), 8.25 (s, 1H), 8.09 (s, 1H), 7.64 (s, 1H), 7.43 (d, J = 6.1 Hz, 2H), 7.34 7.29 (m, 3H), 7.17 (s, 1H), 7.14 (s, 1H), 6.67 (s, 1H), 6.28 (s, 1H), 5.43 (s, 2H); 13 C NMR (101 MHz, CDCl 3 ) δ 163.0, 138.6, 135.1, 133.6, 133.4, 131.9 (2C), 128.8, 128.4, S4
126.8, 126.5, 122.4, 117.6, 109.7, 86.0, 83.8, 39.4; IR (ATR, cm -1 ) 2875, 1637, 1514, 1423, 1399, 1281, 1223, 1070, 1028, 689, 645; HRMS for C 19 H 16 N 3 OS [M+H] + : 334.10086. Found: 334.10492. N'-((1-(3-phenylprop-2-yn-1-yl)-1H-pyrrol-2-yl)methylene)formohydrazide (12h). O Pyrrole aldehyde 10 (209 mg, mmol) and formohydrazide (60 mg, N NH H mmol) were reacted as described above. After evaporation, it was N re-crystallized from MeOH to give the product as brown crystals (221 mg, 88%, NMR yield), mp. 127-129 C. 1 H NMR (400 MHz, CDCl 3 ) δ 10.59 (bs, 1H), 8.75 (d, J = 9.3 Hz, 1H), 7.88 (s, 1H), 7.44 (dd, J = 7.1, 2.2 Hz, 2H), 7.32 (m, 3H), 7.15 (bs, 1H), 6.52 (dd, J = 3.4, 1.2 Hz), 6.23 (t, J = 3.1 Hz), 5.34 (s, 2H); 13 C NMR (101 MHz, CDCl 3 ) δ 165.6, 139.7, 131.9, 128.7, 128.5, 126.9, 126.0, 122.4, 117.6, 109.3, 85.7, 83.6, 39.6; IR (ATR, cm -1 ) 1684, 1425, 1359, 1283, 1219, 1172, 1115, 751, 716, 687; HRMS for C 15 H 14 N 3 O [M+H] + : 252.11314. Found: 252.11657. General Procedure for pyrrole-fused C,Nˈ-cyclic azomethine imine derivatives 13a-h. Hydrazone 12a-h (0.10 g, 0.53 mmol) and 5 mole % CF 3 SO 3 Ag were stirred in 3 ml of CHCl 3 at room temperature for 3 hours. The solvent was evaporated to give the desired cyclization products 13a-h. (3-Methylpyrrolo[1,2-a]pyrazin-2-ium-2-yl)(formyl)amide (13a) Hydrazone 12a (0.10 g, NCHO 0.57 mmol) was reacted as described above to give dark red oily N compund (0.10 g, 89%, NMR yield). 1 H NMR (400 MHz, CDCl 3 ) δ N CH 3 8.94 (s, 1H), 8.19 (d, J = 1.7 Hz, 1H), 8.00 (s, 1H), 7.74 (s, 1H), 7.20 (dd, J = 3.3, 1.0 Hz, 1H), 7.13 7.10 (m, 1H), 2.46 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 191.5, 165.2, 139.4, 130.0, 125.8, 120.1, 118.5, 112.2, 15.8; IR (ATR, cm -1 ) 2917, 1653, 1558, 1541, 1541, 1457, 1419, 1173, 1078, 718; HRMS for C 9 H 10 N 3 O [M+H] + : 176.08184. Found: 176.08366. Acetyl(3-methylpyrrolo[1,2-a]pyrazin-2-ium-2-yl)amide (13b) Hydrazone 12b (0.10 g, 0.53 mmol) was reacted as described above to give red dark oily compound (0.10 g, 99%, NMR yield). 1 H NMR (400 MHz, CDCl 3 ) δ 8.74 (s, 1H), 8.03 (s, 1H), 7.75 (s, 1H), 7.14 (d, J = 4.1 Hz, 1H), 7.05 (dd, J = 4.4, 2.4 Hz, 1H), 2.37 (s, 3H), 2.11 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 173.9, 139.7, 130.2, 125.8, 120.5, 120.0, 118.5, 112.3, 22.2, 15.5; IR (ATR, cm -1 ) 1653, 1558, 1541, 1419, 1373, 1273, 1242, 719; HRMS for C 10 H 11 N 3 O [M+H] + : 190.09749. Found: 190.09729. S5
Benzoyl(3-methylpyrrolo[1,2-a]pyrazin-2-ium-2-yl)amide (13c). Hydrazone 12c (0.10 g, 0.40 mmol) was reacted as described above to give reddish oily compound (0.10 g, 100%, NMR yield). 1 H NMR (400 MHz, CDCl 3 ) δ 9.09 (s, 1H), 8.18 8.16 (m, 2H), 7.94 (bs, 1H), 7.63 (bd, J = 2.1 Hz, 1H), 7.44 7.39 (m, 3H), 7.11 (bd, A-part of AB-system, J = 4.4 Hz, 1H), 7.06 (dd, B-part of AB-system, J = 4.4, 2.4 Hz, 1H), 2.48 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 171.0, 139.0, 137.6, 130.4, 130.1, 128.1, 128.0, 126.0, 119.2, 118.9, 118.4, 110.6, 15.8; IR (ATR, cm -1 ) 1653, 1558, 1370, 1246, 1160, 1028, 745, 636. (3-Methylpyrrolo[1,2-a]pyrazin-2-ium-2-yl)(tosyl)amide (13d). Hydrazone 12d (0.30 g, mmol) and 1 wt % AuCl 3 were stirred in 3 ml of CHCl 3 at room NTs N temperature for 3 hours. The solvent was evaporated to give the product N CH 13d as green powder (0.30 g, 100%, NMR yield), mp. 151-153 C. 1 3 H NMR (400 MHz, DMSO-d 6 ) δ 9.13 (s, 1H), 8.41 (d, J = 0.7 Hz, 1H), 8.04 (t, J = 1.2 Hz, 1H), 7.38 7.35 (m, 3H), 7.23 7.20 (m, 3H), 2.32 (s, 3H), 1.82 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 141.6, 141.4, 140.4, 130.0, 129.2, 125.9, 125.6, 120.9, 119.5, 118.9, 112.2, 20.8, 15.0; IR (ATR, cm -1 ) 3079, 1653, 1558, 1424, 1268, 1136, 1083, 1039, 918, 753, 656, 535; HRMS for C 15 H 16 N 3 O 2 S [M+H] + : 302.09577: Found 302.09760. (3-Methylpyrrolo[1,2-a]pyrazin-2-ium-2-yl)(thiophene-2-carbonyl)amide (13e) Hydrazone 12e (0.10 g, 0.39 mmol) was reacted as described above to give reddish oily compound (0.10 g, 90%, NMR yield). 1 H NMR (400 MHz, CDCl 3 ) δ 8.95 (s, 1H), 7.92 (s, 1H), 7.79 (d, J = 3.5 Hz, 1H), 7.67 (s, 1H), 7.34 (d, J = 4.9 Hz, 1H), 7.16 (d, J = 4.3 Hz, 1H), 7.09 (dd, J = 4.3, 2.4 Hz, 1H), 7.07 (dd, J = 4.7, 4.0 Hz, 1H), 2.44 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 166.9, 140.0, 139.8, 130.3, 129.8, 128.6, 127.6, 125.8, 120.3, 120.0, 118.5, 112.4, 15.6; IR (ATR, cm -1 ) 3078, 1652, 1558, 1458, 1418, 1252, 1160, 1027, 717, 636; HRMS for C 13 H 12 N 3 OS [M+H] + : 258.06956. Found: 258.07205. Benzoyl(3-benzylpyrrolo[1,2-a]pyrazin-2-ium-2-yl)amide (13f) Hydrazone 12f (100 mg, 0.31 mmol) was reacted as described above to give dark red oily compound (79 mg, 78%). 1 H NMR (400 MHz, CDCl 3 ) δ 9.15 (s, 1H), 8.16 (d, J = 7.3 Hz, 2H), 7.55 (s, 1H), 7.49 7.28 (m, 8H), 7.26 (d, J = 1.0 Hz, 1H), 7.16 (d, J = 4.0 Hz, 1H), 7.07 (dd, J = 3.9, 2.3 Hz, 1H), 4.25 (s, 2H); 13 C NMR (101 MHz, CDCl 3 ) δ 170.6, 139.6, 136.9, 135.6, 134.2, 130.5, 129.9, 129.2, 128.2, 128.1, 127.6, 125.7, 119.9, 119.6, 119.4, 111.4, 34.9; IR (ATR, cm -1 ) 3062, S6
2919, 1653, 1527, 1343, 1281, 1252, 1155, 1028, 696; HRMS for C 21 H 18 N 3 O [M+H] + : 328.14444. Found: 328.14899. (3-Benzylpyrrolo[1,2-a]pyrazin-2-ium-2-yl)(thiophene-2-carbonyl)amide (13g) Hydrazone 12g (50 mg, 0.15 mmol) was reacted as described above. After evaporation of the solvent, the column chromatography was carried out on silica gel (10 g) eluting with hexane/etoac (1:1) followed by EtOAc to give 13g as dark red oily compund (27 mg, 54%, NMR yield). 1 H NMR (400 MHz, CDCl 3 ) δ 8.88 (s, 1H), 7.69 (d, J = 2.8 Hz, 1H), 7.52 (s, 1H), 7.37 (s, 1H), 7.25 7.08 (m, 7H), 6.96 (dd, J = 4.4, 2.3 Hz, 1H), 6.94 (dd, J = 4.8, 3.9 Hz, 1H), 4.05 (s, 2H); 13 C NMR (101 MHz, CDCl 3 ) δ 165.7, 140.7, 134.9, 133.9, 130.2, 129.8, 129.5, 129.5, 129.2, 127.8, 127.7, 125.6, 121.6, 120.6, 119.4, 113.6, 34.7; IR (ATR, cm -1 ) 2916, 1653, 1579, 1510, 1415, 1314, 1280, 1208, 1028, 719, 703; HRMS for C 19 H 16 N 3 OS [M+H] + : 334.10086. Found: 334.10521. (3-Benzylpyrrolo[1,2-a]pyrazin-2-ium-2-yl)(formyl)amide (13h) Hydrazone 12h (50 mg, 0.20 mmol) was reacted as described above. After evaporation of the solvent, the column chromatography was carried out on 10 g silica gel eluting with hexane/etoac (1:1) followed by EtOAc to give dark red oily compound 13h (47 mg, 93%, NMR yield). 1 H NMR (400 MHz, CDCl 3 ) δ 8.98 (s, 1H), 8.17 (s, 1H), 7.54 (s, 1H), 7.43 7.30 (m, J = 6.9 Hz, 6H), 7.17 (d, J = 4.3 Hz, 1H), 7.07 (dd, J = 4.4, 2.4 Hz, 1H), 4.20 (s, 2H); 13 C NMR (101 MHz, CDCl 3 ) δ 175.5, 164.8, 140.0, 134.7, 133.7, 130.0, 129.4, 127.9, 125.6, 121.4, 120.7, 119.5, 34.7; IR (ATR, cm -1 ) 2919, 1676, 1654, 1492, 1355, 1256, 1074, 1028, 725, 697; HRMS for C 15 H 14 N 3 O [M+H] + : 252.11314. Found: 252.11668. General Procedure for Cycloaddition Reactions: Synthesis of 14-17. Dipolaphile (1 mmol) was added to a solution of (3-methylpyrrolo[1,2-a]pyrazin-2-ium-2-yl)(tosyl)amide (13d) (1 mmol) in 15 ml of toluene. The resulting mixture was heated at the reflux temperature for 18 h. After cooling to room temperature, the solvent was evaporated under the reduced pressure. The crude product was purified over silica gel eluting with hexane/etoac (10:1 2:1) to give the product. 5-Methylpyrazolo[1,5-a]pyrrolo[2,1-c]pyrazine-1-carbonitrile (14) (3-Methylpyrrolo[1,2- a]pyrazin-2-ium-2-yl)(tosyl)amide (13d) (140 mg, 0.46 mmol) and S7
acrylonitrile (30 µl, 0.46 mmol) were reacted as described above. White needles from chloroform/hexane (40 mg, 44%), mp.: 227 228 C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.03 (s, 1H), 7.30 (bs, 1H), 7.27 (dd, J = 2.7, 1.3 Hz, 1H), 7.18 (bd, J = 4.0 Hz, 1H), 6.76 (dd, J = 4.0, 2.7 Hz, 1H), 2.58 (d, J = 1.2 Hz, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 143.1, 136.4, 122.0, 120.0, 116.8, 114.1, 113.8, 112.0, 105.3, 83.3, 14.7; IR (KBr, cm-1) 3100, 2223, 1587, 1443, 1421, 989, 882, 824, 728, 710, 644; HRMS for C 11 H 9 N 4 [M+H] + : calculated 197.08217, found: 197.0829. HRMS for C 11 H 9 N 4 [M+H] + : 197.08217. Found: 197.0829. 5-Methylpyrazolo[1,5-a]pyrrolo[2,1-c]pyrazine-1-carbaldehyde (15) (3- Methylpyrrolo-[1,2-a]pyrazin-2-ium-2-yl)(tosyl)amide (13d) (150 mg, 0.5 mmol) and acrolein (33 µl, 0.5 mmol) were reacted as described above. The crude product was purified over silica gel eluting with hexane/etoac (5:1 2:1) to give 15. White powder from (50 mg, 50%) mp. 111-112 C. 1 H- NMR (400 MHz, CDCl 3 ) δ 10.10 (s, 1H), 8.23 (s, 1H), 7.69 (d, J = 4.0 Hz, 1H), 7.33 (s, 1H), 7.30 (dd, J = 2.6, 1.4 Hz, 1H), 6.75 (dd, J = 4.0, 2.6 Hz, 1H), 2.59 (d, J = 1.1 Hz, 3H); 13 C- NMR (101 MHz, CDCl 3 ) δ 182.9, 144.3, 133.4, 121.4, 121.3, 117. 1, 116.2, 113.3, 112.1, 108. 8, 14.9; IR (KBr, cm -1 ) 3101, 1661, 1565, 1532, 1360, 1235, 805, 726, 645; HRMS for [M+H] + : C 11 H 10 N 3 O 200.08184 Found: 200.0835. Methyl 5-methylpyrazolo[1,5-a]pyrrolo[2,1-c]pyrazine-1-carboxylate (16) (3-Methyl-pyrrolo-[1,2-a]pyrazin-2-ium-2-yl)(tosyl)amide (13d) (150 mg, 0.5 mmol) and acrolein (50 µl, 0.5 mmol) were reacted as described above. The crude product was purified over silica gel eluting with hexane/etoac (10:1 3:1) to give 16. White needles, (50 mg, 44%) from diethyl ether, mp. 95-97 C. 1 H-NMR (400 MHz, CDCl 3 ) δ 8.20 (s, 1H), 7.70 (ddd, J = 4.0, 1.4, 0.7 Hz, 1H), 7.23 (bs, 1H), 7.22 (dd, J = 2.6, 1.4 Hz, 1H), 6.70 (dd, J = 4.0, 2.6 Hz, 1H), 3.93 (s, 3H), 2.55 (d, J = 1.2 Hz, 3H); 13 C-NMR (101 MHz, CDCl 3 ) δ 163. 6, 143.2, 134.4, 121.7, 121.3, 116.6, 112.9, 111.5, 108.8, 106.0, 51.4, 14.9; IR (KBr, cm - 1) 2923, 1713, 1578, 1535, 1422, 1266, 1246, 1130, 1050, 992, 769, 701, 625; HRMS for C 12 H 12 N 3 O 2 [M+H] + : 230.0924. Found: 230.0942. Dimethyl 5-methylpyrazolo[1,5-a]pyrrolo[2,1-c]pyrazine-1,2-dicarboxylate (17) (3- Methyl-pyrrolo-[1,2-a]pyrazin-2-ium-2-yl)(tosyl)amide (13d) (170 mg, 0.56 mmol) and dimethyl acetylenedicarboxylate (71 µl, 0.56 mmol) were reacted as described above. The crude product was purified over silica gel eluting with hexane/etoac (10:1 2:1). S8
White crystals from chloroform in petroleum ether atmosphere (60 mg, 37%), mp. 147-148 C. 1 H-NMR (400 MHz, CDCl 3 ) δ 7.54 (bd, J = 3.9 Hz, 1H), 7.31 (bs, 1H), 7.24 (dd, J = 2.7, 1.4 Hz, 1H), 6.71 (dd, J = 3.9, 2.7 Hz, 1H), 4.00 (s, 3H), 3.94 (s, 3H), 2.57 (d, J = 0.9 Hz, 3H); 13 C-NMR (101 MHz, CDCl 3 ) δ 163.8, 162.9, 145.9, 134.8, 121.6, 120.6, 117.1, 113.1, 112.7, 109.0, 105.1, 53.0, 52.0, 14.8; IR (KBr, cm -1 ) 2956, 1707, 1566, 1436, 1422, 1353, 1267,1183, 1072, 771, 732; HRMS for C 14 H 13 N 3 NaO 4 [M+Na] + : 310.07983. Found: 310.0810. S9
NMR Spectra 179.8 165.2 139.3 127.0 117.8 109.5 78.4 73.9 38.8 1.01 1.04 1.01 2.05 1.02 9.76 9.74 8.73 8.70 7.79 7.05 7.04 6.49 6.49 6.48 6.48 6.22 6.22 6.21 6.21 5.13 5.13 2.42 N O H N C NH N O H N C NH Figure 1. 1 H and 13 C NMR Spectra of 12a in CDCl 3 (400 MHz) S10
171.6 165.0 138.5 135.5 126.8 126.5 126.5 126.4 115.3 114.7 109.1 108.7 79.9 79.7 75.7 75.2 38.0 37.1 21.6 20.4 0.38 0.38 1.03 1.39 0.39 1.01 0.38 1.01 0.77 2.05 0.38 1.37 3.10 1.14 7.06 7.06 7.05 7.04 6.49 6.49 6.48 6.48 6.43 6.43 6.43 6.42 6.15 6.14 6.14 6.13 6.12 6.11 6.11 6.10 5.20 5.19 5.11 5.10 11.11 10.97 8.08 7.89 7.06 7.06 7.05 7.04 6.43 6.43 6.42 6.11 6.11 6.10 5.20 5.19 5.11 5.10 3.40 3.40 3.39 3.35 3.34 3.34 2.16 1.91 Figure 2. 1 H and 13 C NMR Spectra of 12b in DMSO (400 MHz) S11
1.02 2.06 3.09 1.03 2.01 11.62 8.40 7.91 7.89 7.89 7.54 7.52 7.12 7.11 6.55 6.55 6.54 6.19 6.18 6.17 5.28 5.28 3.43 3.43 3.42 N O N C NH 162.6 140.5 133.6 131.5 128.4 127.4 126.7 126.6 115.1 109.2 79.6 75.7 37.1 N O N C NH Figure 3. 1 H and 13 C NMR Spectra of 12c in DMSO (400 MHz) S12
144.3 142.2 135.3 129.8 128.2 127.1 125.7 118.0 109.4 78.4 73.9 38.6 21.7 2.17 1.05 2.13 1.07 1.06 1.04 2.08 3.09 7.87 7.85 7.72 7.31 7.29 7.02 7.02 7.01 6.38 6.38 6.37 6.37 6.14 6.14 6.13 8.16 7.87 7.85 7.72 7.31 7.29 7.02 7.02 7.01 6.38 6.38 6.37 6.37 6.15 6.14 6.14 6.13 5.00 4.99 2.40 2.37 2.37 2.36 N O N S NH O N O N S NH O Figure 4. 1 H and 13 C NMR Spectra of 12d in CDCl 3 (400 MHz) S13
160.9 157.3 140.3 138.5 134.1 134.0 131.5 128.5 128.0 126.8 126.6 126.4 115.2 114.4 109.2 79.7 79.5 76.2 75.8 37.1 37.0 0.58 0.55 0.57 0.61 1.95 1.58 1.55 0.58 0.97 1.54 2.03 1.11 0.55 11.66 11.54 8.37 8.12 8.03 7.92 7.91 7.87 7.86 7.85 7.84 7.21 7.20 7.11 6.64 6.56 6.56 6.19 6.18 6.17 5.25 5.15 3.47 3.43 Figure 5. 1 H and 13 C NMR Spectra of 12e in DMSO (400 MHz) S14
162.7 140.7 133.6 131.5 128.8 128.6 128.4 127.5 126.8 126.7 121.8 115.2 109.2 85.4 84.2 48.6 37.9 1.03 2.23 10.14 1.06 1.02 2.11 11.68 8.47 7.91 7.52 7.37 7.37 7.36 7.36 7.36 6.59 6.59 6.59 6.58 6.21 6.21 5.55 Figure 6. 1 H and 13 C NMR Spectra of 12f in DMSO (400 MHz) S15
163.0 138.6 135.1 133.6 133.4 131.9 128.7 128.4 126.8 126.5 122.4 117.6 109.6 86.0 83.8 39.4 1.09 1.02 1.02 2.21 2.93 2.06 1.04 1.11 2.36 0.20 1 8.25 8.09 7.44 7.43 7.31 7.29 7.17 6.67 7.14 6.28 5.43 3.50 Figure 7. 1 H and 13 C NMR Spectra of 12g in CDCl 3 (400 MHz) S16
165.6 139.7 131.9 128.7 128.4 126.9 126.0 122.4 117.6 109.3 85.6 83.6 39.6 1.04 1.01 2.10 3.06 1.05 1.03 1.06 2.03 10.59 8.76 8.73 7.88 7.44 7.43 7.33 7.32 7.31 6.52 6.52 6.51 6.24 6.23 6.22 5.34 Figure 8. 1 H and 13 C NMR Spectra of 12h in CDCl 3 (400 MHz) S17
191.5 165.2 139.4 130.0 125.8 120.1 118.5 112.2 15.8 1.09 1.01 1.03 1.06 1.04 3.03 8.94 8.19 8.19 8.00 7.74 7.21 7.21 7.20 7.20 7.13 7.13 7.12 7.11 7.11 2.46 Figure 9. 1 H and 13 C NMR Spectra of 13a in CDCl 3 (400 MHz) S18
173.9 139.7 130.1 125.8 120.5 120.0 118.5 112.3 22.2 15.5 1.04 1.02 1.03 1.02 3.04 3.13 8.74 8.03 7.75 7.15 7.14 7.05 7.05 7.04 7.04 2.37 2.11 Figure 10. 1 H and 13 C NMR Spectra of 13b in CDCl 3 (400 MHz) S19
2.08 1.03 1.08 3.10 1.01 3.11 9.09 8.18 8.18 8.17 8.16 8.16 7.94 7.63 7.63 7.43 7.43 7.42 7.41 7.12 7.10 7.07 7.07 7.06 7.06 2.48 N O N C N 8.18 8.18 8.17 8.16 8.16 7.94 7.63 7.63 7.43 7.43 7.42 7.41 7.12 7.10 7.07 7.07 7.06 7.06 N O N C N Figure 11. 1 H and 13 C NMR Spectra of 13c in CDCl 3 (400 MHz) S20
141.6 141.4 140.4 129.2 125.9 125.6 120.9 119.5 118.9 112.2 20.8 15.0 1.04 1.06 3.18 3.18 3.15 3.10 9.13 8.42 8.41 8.05 8.04 7.38 7.37 7.35 7.22 7.21 7.21 7.20 2.32 1.82 Figure 12. 1 H and 13 C NMR Spectra of 13d in DMSO (400 MHz) S21
166.9 140.0 139.8 130.3 129.8 128.5 127.5 125.8 120.3 120.0 118.4 112.4 15.6 1.13 1.08 1.05 1.03 1.04 2.10 8.95 7.92 7.79 7.78 7.67 7.35 7.33 7.17 7.16 7.09 7.09 7.08 7.08 7.07 7.06 2.44 Figure 13. 1 H and 13 C NMR Spectra of 13e in CDCl 3 (400 MHz) S22
170.6 139.6 135.6 134.2 130.5 129.9 129.2 128.2 128.1 127.6 125.7 119.9 119.6 119.4 111.4 34.9 2.08 1.10 8.05 1.05 1.01 1.03 2.08 8.17 8.15 7.55 7.46 7.44 7.42 7.40 7.38 7.36 7.34 7.32 7.31 7.30 7.26 7.26 7.17 7.16 7.07 7.07 7.06 9.15 8.17 8.15 7.55 7.46 7.44 7.42 7.40 7.38 7.36 7.34 7.32 7.31 7.30 7.26 7.26 7.17 7.16 7.07 7.07 7.06 4.26 Figure 14. 1 H and 13 C NMR Spectra of 13f in CDCl 3 (400 MHz) S23
165.7 140.7 133.9 130.2 129.8 129.2 127.8 127.7 125.6 120.6 119.4 113.6 34.7 1.08 1.05 1.15 1.12 7.23 1.07 1.11 2.06 7.69 7.68 7.52 7.37 7.27 7.26 7.22 7.20 7.18 7.16 7.15 7.13 7.11 6.97 6.97 6.96 6.96 6.95 6.94 6.93 6.92 8.88 7.69 7.68 7.52 7.37 7.27 7.26 7.22 7.20 7.18 7.16 7.15 7.13 7.11 6.97 6.97 6.96 6.96 6.95 6.94 6.93 6.92 4.05 Figure 15. 1 H and 13 C NMR Spectra of 13g in CDCl 3 (400 MHz) S24
175.5 164.7 140.0 134.7 133.7 130.0 129.4 127.9 125.6 121.4 120.7 119.5 34.7 1.01 1.06 6.37 1.10 1.03 7.54 7.42 7.42 7.41 7.40 7.39 7.38 7.36 7.35 7.34 7.34 7.33 7.30 7.29 7.26 7.17 7.16 7.08 7.08 7.07 7.06 8.98 8.17 7.54 7.42 7.42 7.41 7.40 7.39 7.38 7.36 7.35 7.34 7.34 7.33 7.30 7.29 7.26 7.17 7.16 7.08 7.08 7.07 7.06 4.20 Figure 16. 1 H and 13 C NMR Spectra of 13h in CDCl 3 (400 MHz) S25
143.1 136.4 122.0 120.0 116.8 114.1 113.8 112.0 105.3 83.3 14.7 1.06 1.02 1.02 1.04 3.01 8.03 7.30 7.27 7.27 7.26 7.18 6.77 6.76 6.76 6.75 7.30 7.27 7.27 7.26 7.18 7.17 6.77 6.76 6.76 6.75 2.59 2.58 Figure 17: 1 H and 13 C NMR Spectra of 14 in CDCl 3 (400 MHz) S26
8.0 7.8 7.6 7.4 7.2 7.0 f1 (ppm) 6.8 6.6 6.4 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 182.9 144.3 133.4 121.8 121.4 117.1 116.2 113.3 112.1 108.8 14.9 Figure 18: 1 H and 13 C NMR Spectra of 15 in CDCl 3 (400 MHz) S27
200 190 180 170 160 150 140 130 120 110 100 f1 (ppm) 90 80 70 60 50 40 30 20 10 0 182.8 144.2 116.9 113.2 112.0 108.7 14.8 182.8 144.2 116.9 113.2 112.0 108.7 Figure 19: DEPT 90 and DEPT 135 Spectra of 14 in CDCl 3 (400 MHz) S28
Figure 20: COSY and HSQC Spectra of 15 in CDCl 3 (400 MHz) S29
Figure 21: HMBC Spectra of 15 in CDCl 3 (400 MHz) S30
163.6 143.2 134.4 121.7 121.3 116.6 112.9 111.5 108.8 106.0 51.4 14.9 1.04 1.05 1.05 3.00 3.07 7.71 7.71 7.71 7.71 7.70 7.70 7.70 7.70 7.23 7.22 7.22 7.21 7.21 6.71 6.70 6.70 6.69 8.20 7.71 7.71 7.70 7.70 7.23 7.22 7.22 6.71 6.70 6.70 6.69 3.93 2.55 2.55 Figure 22: 1 H and 13 C NMR Spectra of 16 in CDCl 3 (400 MHz) S31
163.8 162.9 145.9 134.8 121.6 120.6 117.1 113.1 112.7 109.0 105.1 53.0 52.0 14.8 1.04 1.01 1.02 3.07 3.09 3.09 7.54 7.53 7.31 7.25 7.24 7.24 7.24 6.71 6.71 6.70 6.70 7.54 7.53 7.31 7.25 7.24 7.24 7.24 6.71 6.71 6.70 6.70 4.00 3.94 2.57 2.57 Figure 23: 1 H and 13 C NMR Spectra of 17 in CDCl 3 (400 MHz) S32
THEORETICAL CALCULATIONS 1. Methodology The quantum chemical calculations were performed using the Gaussian 09 program package 1 and the structures were fully optimized at the RHF/6-311 G(d,p) level of theory without constraints. NICS values were computed on the basis of RHF/6-311 G(d,p) geometries of molecules using the gaugeincluding atomic orbital (GIAO) method at the RHF/6-311 G(d,p) theory level. 1b-d Coordinates for 13a Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------- 1 6 C 3.051727 0.455802 0.357422 2 6 C 3.470104-0.823390 0.182183 3 6 C 2.344876-1.578843-0.163013 4 6 C 1.297995-0.724243-0.181098 5 7 N 1.729697 0.484793 0.130213 6 1 H 3.664984 1.289911 0.627751 7 1 H 4.471413-1.185415 0.288091 8 1 H 2.318066-2.627915-0.371884 9 6 C -0.043266-0.995182-0.470062 10 6 C 0.818916 1.617259 0.190167 11 1 H -0.354971-1.988240-0.718206 12 6 C -0.486156 1.366287-0.088543 13 6 C -1.519852 2.507112-0.048620 14 1 H -1.931127 2.581453 0.936381 15 1 H -1.043068 3.429617-0.306613 16 1 H -2.303579 2.302916-0.747888 17 7 N -0.911605-0.017003-0.432661 18 7 N -2.257225-0.275395-0.719958 19 1 H 1.160437 2.599654 0.441492 20 6 C -3.180566-0.650654 0.360561 21 8 O -3.339133-1.862535 0.660180 22 1 H -3.717830 0.106645 0.892300 -------------------------------------------------------------------- Coordinates for 13c Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 C -4.270029-1.104112 0.811944 2 6 C -5.002602 0.037115 0.866852 3 6 C -4.202207 1.062862 0.353805 4 6 C -3.023300 0.497139 0.012102 5 7 N -3.074090-0.793523 0.288979 S33
6 1 H -4.588483-2.075390 1.128340 7 1 H -6.003228 0.133775 1.233330 8 1 H -4.470617 2.093614 0.251793 9 6 C -1.893707 1.105385-0.544628 10 6 C -1.939997-1.665328 0.025566 11 1 H -1.890517 2.154496-0.754997 12 6 C -0.837354-1.085846-0.515045 13 6 C 0.409507-1.934300-0.826595 14 1 H 1.055046-1.946321 0.026654 15 1 H 0.110682-2.934423-1.061876 16 1 H 0.929119-1.511665-1.661031 17 7 N -0.840767 0.373282-0.804611 18 7 N 0.296238 0.970401-1.361986 19 1 H -1.972949-2.711675 0.246864 20 6 C 1.343386 1.516684-0.486798 21 8 O 1.285862 2.715860-0.109653 22 6 C 2.510798 0.621456-0.031477 23 6 C 3.127002 0.849237 1.206396 24 6 C 2.956938-0.420983-0.855008 25 6 C 4.189343 0.034577 1.620741 26 1 H 2.786366 1.645164 1.835179 27 6 C 4.019280-1.235643-0.440663 28 1 H 2.486455-0.594896-1.800153 29 6 C 4.635481-7864 0.797212 30 1 H 4.659825 0.208491 2.565887 31 1 H 4.359917-2.031569-1.069446 32 1 H 5.446600-1.629877 1.113576 ---------------------------------------------------------------------- Coordinates for 13d Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------- 1 6 C 4.410242-1.778416-0.168713 2 6 C 5.015116-1.018411-1.164902 3 6 C 4.262068 0.147163-1.362585 4 6 C 3.183705 0.090334-0.475999 5 7 N 3.297975-1.111086 0.250567 6 1 H 4.689361-2.725037 0.263988 7 1 H 5.916166-1.295633-1.689479 8 1 H 4.454891 0.943464-2.062796 9 6 C 2.116175 0.937696-0.182391 10 6 C 2.366098-1.413455 1.219061 11 1 H 1.976395 1.878595-0.689530 12 6 C 1.320182-0.588342 1.468016 13 6 C 0.286733-0.875440 2.508327 14 1 H -0.708825-0.919102 2.063623 15 1 H 0.508195-1.827314 2.993932 16 1 H 0.262704-0.080008 3.255207 17 7 N 1.194018 0.609132 0.731292 S34
18 7 N 0.163155 1.453698 1.105622 19 16 S -0.847709 1.910945-0.123736 20 6 C -2.046585 0.568725-0.296551 21 6 C -1.893378-0.381733-1.301042 22 6 C -3.100142 0.474470 0.613210 23 6 C -2.801085-1.435925-1.390074 24 1 H -1.088603-0.275148-2.017325 25 6 C -3.997314-0.581411 0.510063 26 1 H -3.218822 1.234700 1.375425 27 6 C -3.863066-1.554770-0.489923 28 1 H -2.684558-2.171476-2.179583 29 1 H -4.821815-0.648338 1.212929 30 6 C -4.865036-2.677073-0.609917 31 1 H -5.147729-3.066372 0.371571 32 1 H -5.782386-2.330972-1.098200 33 1 H -4.469057-3.504249-1.202583 34 8 O -0.150005 1.983446-1.423533 35 8 O -1.571934 3.067283 0.392110 36 1 H 2.504623-2.336745 1.762155 -------------------------------------------------------------------- Coordinates 13f Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 C 3.835068-1.630654 1.160651 2 6 C 4.169345-2.925589 0.929391 3 6 C 3.140870-3.483721 0.163403 4 6 C 2.232051-2.503066-0.034054 5 7 N 2.654989-1.403685 0.563888 6 1 H 4.408623-0.919688 1.717841 7 1 H 5.052652-3.425002 1.268884 8 1 H 3.084560-4.490008-0.195922 9 6 C 1.025541-2.562053-0.738855 10 6 C 1.876321-0.175918 0.520765 11 1 H 0.716459-3.471501-1.210313 12 6 C 0.702756-0.221123-0.160837 13 6 C -0.185452 1.033201-0.257578 14 1 H -0.870770 1.049180 0.563995 15 1 H -0.731745 1.013318-1.177398 16 7 N 0.280029-1.489263-0.813554 17 7 N -0.929986-1.535510-1.516209 18 1 H 2.211707 0.718771 2376 19 6 C -2.170483-1.906215-0.820044 20 8 O -2.522487-3.112949-0.761260 21 6 C -3.039278-0.817796-0.162670 22 6 C -3.806448-1.122705 0.969762 23 6 C -3.062711 0.477573-0.696892 24 6 C -4.597048-0.132244 1.567976 25 1 H -3.788559-2.111749 1.377649 S35
26 6 C -3.853311 1.468034-0.098677 27 1 H -2.476963 0.710376-1.561530 28 6 C -4.620479 1.163126 1.033756 29 1 H -5.182796-0.365048 2.432615 30 1 H -3.871202 2.457078-0.506566 31 1 H -5.224117 1.919366 1.490509 32 6 C 0.698940 2.293144-0.212919 33 6 C 1.273510 2.783971-1.385706 34 6 C 0.925470 2.943691 0.999937 35 6 C 2.074965 3.924703-1.345446 36 1 H 1.095351 2.270420-2.341618 37 6 C 1.726343 4.085352 1.040226 38 1 H 0.472552 2.557081 1.924344 39 6 C 2.301194 4.575845-0.132165 40 1 H 2.528392 4.311275-2.269709 41 1 H 1.904442 4.598308 1.996590 42 1 H 2.933101 5.475288-0.100677 ------------------------------------------------------------------------ Coordinates for 14 Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 C 0.259741 1.073017-0.000061 2 6 C -0.571620-0.080182-0.000035 3 6 C 1.403346-1.526269 0.000190 4 6 C 2.189781-0.429596 0.000151 5 6 C 2.286142 2.062798-0.000090 6 6 C 1.324682 3.054437-0.000083 7 6 C 0.050829 2.442463-0.000160 8 1 H 3.267182-0.497302 0.000197 9 1 H 3.362311 2.118825-0.000089 10 1 H 1.524224 4.114479-0.000095 11 1 H -0.910458 2.930034-0.000226 12 6 C 1.895831-2.936654 0.000302 13 1 H 2.985982-2.951802 0.000405 14 1 H 1.529974-3.474852 0.878055 15 1 H 1.530139-3.474935-0.877469 16 7 N 1.644753 0.848906 0.000032 17 7 N 0.021109-1.320846 0.000096 18 6 C -1.949206-0.325715-0.000081 19 6 C -2.060157-1.740505-0.000030 20 7 N -0.882900-2.339988 0.000126 21 1 H -2.967045-2.325685-0.000055 22 6 C -2.986941 0.629713-0.000198 23 7 N -3.836802 1.414814-0.000274 ----------------------------------------------------------------------------------- Coordinates for 15 S36
Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------------------- 1 6 C -0.490637 0.899984-0.000195 2 6 C -0.322476-0.512682-0.000237 3 6 C 2.144745-0.209088-0.000092 4 6 C 1.975008 1.144645 0.000341 5 6 C 0.306326 3.054234 0.000421 6 6 C -1.086393 3.089609-0.000671 7 6 C -1.585812 1.761238-0.000500 8 1 H 2.825902 1.839273 0.000901 9 1 H 1.015313 3.881941 0.000668 10 1 H -1.696594 3.990066-0.001185 11 1 H -2.634049 1.469500-0.001036 12 6 C 3.492899-0.834409 0.000169 13 1 H 4.283910-0.072146 0.000036 14 1 H 3.641800-1.466978 0.887026 15 1 H 3.641754-1.467177-0.886609 16 7 N 0.683260 1.710104 0.000218 17 7 N 0.987384-1.040887-0.000708 18 6 C -1.178592-1.622180 0.000104 19 6 C -0.348421-2.783736-0.000235 20 7 N 0.952594-2.416490-0.000549 21 1 H -0.647746-3.832220-0.000290 22 6 C -2.718333-1.593945 0.000725 23 1 H -3.268415-2.511719 0.000943 24 8 O -3.331803-0.495207 0.000977 ---------------------------------------------------------------------------------- Coordinates for 16 Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------------------- 1 6 C 0.429610 1.041953-0.000270 2 6 C -0.229420-0.218833-0.000312 3 6 C 1.978135-1.361659-0.000167 4 6 C 2.602582-0.148618 0.000266 5 6 C 2.303930 2.369683 0.000346 6 6 C 1.174553 3.185418-0.000746 7 6 C 0.012201 2.371214-0.000575 8 1 H 3.697084-0.055914 0.000826 9 1 H 3.356480 2.652354 0.000593 10 1 H 1.179514 4.273142-0.001260 11 1 H -1.017626 2.722450-0.001111 12 6 C 2.737561-2.639085 0.000094 13 1 H 3.820841-2.456746-0.000039 14 1 H 2.503198-3.245212 0.886951 15 1 H 2.503047-3.245350-0.886684 16 7 N 1.855899 1.047551 0.000143 17 7 N 0.553250-1.394487-0.000783 S37
18 6 C -1.562530-0.650964 0.000029 19 6 C -1.533416-2.078391-0.000310 20 7 N -0.252336-2.510070-0.000624 21 1 H -2.372571-2.774619-0.000365 22 6 C -2.817272 0.241910 0.000649 23 8 O -2.703029 1.495113 0.000901 24 8 O -4.116669-0.355137 0.000941 25 1 H -4.785681 0.333356 0.001206 ------------------------------------------------------------------------------- Coordinates for 17 Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------- 1 6 C 1.902979-0.961786 0.004470 2 6 C 0.829480-0.029673-0.047183 3 6 C 2.464334 1.841778 0.018207 4 6 C 3.488248 0.941439 0.067126 5 6 C 4.130896-1.511428 0.105588 6 6 C 3.378910-2.683888 0.077786 7 6 C 2.000657-2.351577 0.014710 8 1 H 4.539776 1.255731 0.112282 9 1 H 5.212827-1.389275 0.153187 10 1 H 3.781011-3.694322 0.100315 11 1 H 1.171501-3.055336-0.018975 12 6 C 2.703591 3.308503 0.022755 13 1 H 3.777412 3.535275 0.069952 14 1 H 2.303760 3.783249-0.884759 15 1 H 2.224412 3.790425 0.887086 16 7 N 3.231149-0.445004 0.061321 17 7 N 1.127510 1.350851-0.038931 18 6 C -0.567899-0.115419-0.109608 19 6 C -1.062501 1.223621-0.136732 20 7 N -0.029177 2.094199-0.093744 21 6 C -1.408177-1.405553-0.142597 22 8 O -0.843961-2.529992-0.113135 23 8 O -2.834483-1.325488-0.206930 24 6 C -2.523803 1.704961-0.203867 25 8 O -3.587269 0.749970-0.247840 26 8 O -2.785259 2.935793-0.220163 27 6 C -3.386221-2.644614-0.226686 28 1 H -3.018177-3.172393-1.081610 29 1 H -3.099996-3.164311 0.663758 30 1 H -4.453328-2.584178-0.276989 31 6 C -3.767337 0.175984 1.049471 32 1 H -4.218074 0.896951 1.699041 33 1 H -4.401576-0.682536 0.974738 34 1 H -2.817097-0.115950 1.445348 -------------------------------------------------------------------------------- Coordinates for 23 S38
Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z -------------------------------------------------------------------------------------- 1 6 C 0.337609-1.131839-0.000030 2 6 C -1285-0.716790-0.000030 3 6 C -0387 0.718081-0.000030 4 6 C 0.339130 1.131448 0.000074 5 7 N 1.148612-0.000744-0.000021 6 1 H 2.132849-0.001503 0.000196 7 1 H 0.761023-2.135444-0.000128 8 1 H -1.875166-1.359569-0.000055 9 1 H -1.873453 1.361954-0.000005 10 1 H 0.764065 2.134371 0.000221 --------------------------------------------------------------------------------------- Coordinates for 24 Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ---------------------------------------------------------------------------------------- 1 6 C -0.651040 0.957605-0.000026 2 6 C 0.750639 0.943526-0.000026 3 6 C 1.160847-0.431460-0.000026 4 7 N -1.104008-0.358420-0.000017 5 1 H -2.047209-0.639662 0.000200 6 1 H -1.344224 1.797843-0.000124 7 1 H 1.403745 1.809716-0.000051 8 1 H 2.181778-0.798224-0.000001 9 7 N -0.004101-1.211251 0.000078 ----------------------------------------------------------------------------------------- Coordinates for 25 Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 C 1.145017-0.710224 0.000028 2 6 C 1.145595 0.709344 0.000028 3 7 N 0.000548 1.422051 0.000028 4 6 C -1.144998 0.710222-0.000020 5 6 C -1.145589-0.709367-0.000033 6 7 N -0.000569-1.422024-0.000034 7 1 H 2.086218-1.284660 0.000080 8 1 H 2.087263 1.282984 0.000064 9 1 H -2.086209 1.284636-0.000041 10 1 H -2.087277-1.283012-0.000083 S39
X-Ray structure determination of 13d For the crystal structure determination, single-crystal of compound 13d was used for data collection on a four-circle Rigaku R-AXIS RAPID-S diffractometer (equipped with a twodimensional area IP detector). Graphite-monochromated Mo-K α radiation (λ = 0.71073 Å) and oscillation scans technique with w = 5º for one image were used for data collection. The lattice parameters were determined by the least-squares methods on the basis of all reflections with F 2 > 2σ(F 2 ). Integration of the intensities, correction for Lorentz and polarization effects and cell refinement was performed using CrystalClear (Rigaku/MSC Inc.,2005) software. 2 The structures were solved by direct methods using SHELXS-97 3 and refined by a full-matrix least-squares procedure using the program SHELXL-97 3. All nonhydrogen atoms were refined anisotropically and H atoms were positioned geometrically and refined using a riding model. The final difference Fourier maps showed no peaks of chemical significance. Crystal data for 13d: C 15 H 15 N 3 O 2 S, crystal system, space group: triclinic, P-1; (no:2); unit cell dimensions: a = 7.6723(2), b = 8.4589(3), c = 12.0070(4) Å, α= 106.051(1), β = 99.601(2), γ = 99.741(1) Å; volume: 719.05(5) Å 3 ; Z = 2; calculated density: 1.39 g/cm 3 ; absorption coefficient: 0.233 mm -1 ; F(000): 316; θ-range for data collection 2.9 27.7º ; refinement method: full matrix least-square on F 2 ; data/parameters: 2009/192; goodness-of-fit on F 2 : 1.031; final R-indices [I > 2σ(I)]: R 1 = 0.047, wr 2 = 0.106; largest diff. peak and hole: 0.190 and -0.243 e Å -3. S40
Fig. 1. Up: Mercury drawing of the molecule 13d. Thermal ellipsoids are drawn at the 50% probability level. Selected bond lengths (Å) ; S1-O1 1.448(2), S1-O2 1.439(2), S1-C9 1.765(2), S1-N3 1.594(2), N3-N2 1.413(3), N2-C5 1.326(3), N2-C7 1.415(3), N1-C1 1.350(3). Down: C-H N interaction along the a-axis Crystallographic data that were deposited in CSD under CCDC-1054476 registration number contain the supplementary crystallographic data for this Letter. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre (CCDC) via S41
www.ccdc.cam.ac.uk/data_request/cif and are available free of charge upon request to CCDC, 12 Union Road, Cambridge, UK (fax: +441223 336033, e-mail: deposit@ccdc.cam.ac.uk). References References (1) (a) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.;Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision A.02; Gaussian, Inc.: Wallingford, CT, 2009. (b) Becke, A. D. J. Chem. Phys. 1993, 98, 5648; (c) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785; (d) Miehlich, B.; Savin, A.; Stoll, H.; Preuss, H. Chem. Phys. Lett. 1989, 157, 200. (2) Rigaku/MSC, Inc.: 9009 new Trails Drive, The Woodlands, TX 77381. (3) Sheldrick, G. M. SHELXS97 and SHELXL97; University of Göttingen: Germany, 1997. S42