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1 J Braz Chem Soc Vol 21 No 6 S1-S Printed in Brazil Sociedade Brasileira de Química $ General remarks through aza-michael Reaction Ihssan Meskini a Loïc Toupet b Maria Daoudi a Abdelali Kerbal a Brahim Bennani a Pierre H Dixneuf c Zahid H Chohan d Ana Cristina Lima Leite* e and Taibi Ben Hadda* f a Laboratoire de Chimie Organique Faculté des Sciences Dhar Mehraz Fès Morocco b Institut de Physique - IPR - UMR 6251 CNRS Université de Rennes 1 Rennes France c Laboratoire Catalyse et Organométalliques Institut Sciences Chimiques de Rennes UMR 6226 CNRS University of Rennes Av Géneral Leclec 5042 Rennes France d Department of Chemistry Bahauddin Zakariya University Multan Pakistan e Department of Pharmaceutical Science Centre for Health Science Federal University of Pernambuco Recife-PE Brazil f Laboratoire Chimie des Matériaux Faculté des Sciences Oujda Morocco All common laboratory chemicals were purchased from commercial sources and used without further purification Melting points were determined using a Thomas Hoover apparatus and are uncorrected Infrared spectra were recorded on a Beckman 10 spectrometer as KBr pellets The 1 H and 1 C NMR spectra were recorded on Bruker AC 00 spectrometer and TMS as an internal standard Coupling constants (J) are given in hertz The FAB mass spectra were obtained on a Hewlett-Packard 5989A Mass Spectrometer (70 ev) Elemental analyses (C N and H) were performed by the Service Central Analyses (CURI Université Sidi Mohamed Ben Abdellah Fès Morocco) and the results lay within the acceptable range (±04%) CCD Saphire Xcalibur diffractometer (Oxford Diffraction) with graphite monochromatized MoKa radiation was used to record the X-ray analysis General procedure To a solution of ethyl malonate (15 g 9 mmol) in 40 ml of ethanol were added the respective aldehyde (100 mmol) 15 ml of piperidine and 1 ml of glacial acetic acid Then the mixture was stirred at refluxing temperature of ethanol for 12 h until thin-layer chromatography indicated the complete consume of the starting material After removing solvent the crude product was washed with a saturated solution of * tbenhadda@yahoofr or analeite@pqcnpqbr sodium bisulfite (20 ml) The product was extracted by diethyl ether (2 x 20 ml) dried with sodium sulphate and evaporated to give the respective pure oil Diethyl 2-benzylidenemalonate (4a): Yellow oil 71% of yield Rf 07 (ether/n-hexane 1/1) IR (KBr): n max /cm (CH) 1722 (C=O) 1629 and1497 (C=C) (C-O) 1 H NMR (00 MHz CDCl ) d: 125 (t H H 2 C-CH J 71 Hz) 11 (t H CH 2 -CH J 71 Hz) 428 (q H CH 2 -CH J 72 Hz) 42 (q 2H CH 2 -CH J 72 Hz) (m 5H Ph) 772 (s 1H C=CH-Ph) 1 C NMR (755 MHz CDCl ) d: 616/616 (2C 2CH 2 -CH ) 141/18 (2C 2CH 2 -CH ) 1261 (C quat =C-) 1287 (2C tert ortho) 1294 (C tert para) 105 (2C tert meta) 128 (C quat Ph) 1420 (Ph-CH) 1666 and 1662 (2C=O) MS (IE): Calc for [M] + C 14 H 16 O 4 : 248 [M+H] + (m/z) = 249 (100%) Diethyl 2-(4-chlorobenzylidene)malonate (4b): Yellow oil 77% yield Rf 07 (ether/hexane 1/1) IR (KBr): n max /cm (CH) 1724 (CO) 1591/161 (C=C) 1254/108 (C-O) 1 H NMR (00 MHz CDCl ) d: (2 t 6H 2H 2 C-CH J 711 Hz) (2 q 4H 2CH 2 -CH J 712 Hz) (m 4H Ph) 77 (s 1H C=CH-ph) 1 C NMR (755 MHz CDCl ) d: 17 and 18 (2CH -CH 2 ) 614 and 617 (2CH 2 -CH ) 1254 (C=C- (CO 2 ) 1290 (2C ortho ) 10 (2C meta ) 104 (C quat para/ Cl) 129 (C quat C-Cl-Ph) 1400 (ClPh-CH=) 166 and 168 (2C=O) MS (IE): Calc for [M] + C 14 H 15 ClO 4 : 28207; [M+H] + = 28 (100%) Supplementary Information

2 S2 J Braz Chem Soc Diethyl 2-(-methoxybenzylidene)malonate (4c): Yellow oil 70% yield Rf 05 (ether/hexane 2/1) IR (KBr): n max /cm (CH) 1754 (C=O) 1254/108 (C-O) 1 H NMR (00 MHz CDCl ) d: (2 t 6H 2H 2 C-CH J 711 Hz) (m 4H 2CH 2 -CH ) 401 (s H CH O) (m 4H Ph) 74 (s 1H C=CH- Ph) 1 C NMR (755 MHz CDCl ) d: 17 and 140 (2CH - CH 2 ) 614 and 601 (2CH 2 -CH ) 1254 (C=C-(CO 2 ) 1254 (C=C-(CO 2 ) 1290 (2C ortho ) 10 (2C meta ) 104 (C quat para/ch O) 129 (C quat Ph-OMe) 1400 (Ph-CH=) 166 and 168 (2C=O) Elemental analysis for C 15 H 18 O 5 Calc (Found): C 6474 (650) H 652 (62)% General procedure for the synthesis of 6-15 To a solution of the intermediate 4a-d (81 mmol) in water (25 ml) was added the respective secondary amine (6 mmol) at the presence or absence of acetic acid (01 ml) and the mixture was stirred at room temperature until the complete consume of the starting materials After removing solvent the crude products were dissolved in diethyl ether (2 40 ml) and washed with water until the ph became neutral The organic solvent was dried with sodium sulphate and then evaporated to give the respective pure compound Diethyl 2-(phenyl(piperidin-1-yl)methyl)malonate (6): White powder mp C Rf = 072 (ether/hexane 1/1) IR (KBr): n max /cm (C-H Ph) 2754/2800 (C-H aliph) 1750/1740 (C=O) 1514/1450 (C=C) 11/1257 (C-O) 1 H NMR (00 MHz CDCl ) d: 100 (t H H 2 C CH J 71 Hz); 126 (m 2H -C H 2 - piper) 15 (t H H 2 C-CH J 71 Hz) 150 (m 4H 2C 2 H 2 piper) 220 (s large 2H C 1 H 2 piper) 259 (s large 2H C 1 H 2 piper) 402 (dq 2H AB O-CH 2 CH 2 J A-B 107 Hz J 69 Hz) 42 (d 1H C 2 H-(CO 2 J 121 Hz) 4 (dq 2H O-CH 2 CH J A-B 02 Hz J 71 Hz) 44 (d 1H ph-c H J 12 Hz) (m 5H Ph) 1 C NMR (755 MHz CDCl ) d: 140/175 (2C 2OCH 2 CH ) 2440 (C C H 2 piper) 2650 (2C 2C 2 H 2 piper) 5055 (2C 2C 1 H 2 piper) 5496 (C tert C 2 H(CO 2 ) 610/ 6115 (2C 2OCH 2 CH ) 6915 (C tert PhC 2 H) 1275 (2C ter t meta Ph) (C tert para Ph) (2C ortho Ph) 19 tert (C quat Ph) 16722/16804 (2C=O) MS (IE): Calc for [M] + : C 19 H 27 NO 4 19 [M+H] + (m/z) = 4 (5%) 174 (100%) Elemental analysis for C 19 H 27 NO 4 Calc (Found): C 6846 (6789) H 840 (789) N 420 (422)% Diethyl 2-((4-chlorophenyl)(morpholino)methyl) malonate (7): White crystals mp C Rf = 055 (ether/ hexane: 1/1) IR (KBr): n max /cm (C H 4-Cl-Ph) (C-H) 1747 (C=O) 1712 (C=O) (C=C) (C-O) 1 H NMR (00 MHz CDCl ) d: 106 (t H OCH 2 CH J 71 Hz) 20 (s 2H C 1 H 2 ) 25 (s 2H C 1 H 2 ) 9 (s 4H C 2 H 2 OC 2 H 2 ) (m 2H OCH 2 CH ) 420 (d 1H C 2 H (CO 2 J 10 Hz) (m H OCH 2 CH + PhC H) 712 (d 2H meta J 80 Hz) 75 (d 2H ortho J 80 Hz) 1 C NMR (755 MHz CDCl ) d: 18 (C OCH 2 CH ester) 14 (C OCH 2 CH ester) 495 (2C 2 C 1 H 2 N morph) 546 (C tert C 2 H(CO 2 ) 615 (C CH 2 OCH ester) 616 (C CH 2 OCH ester) 671 (2C 2C 2 H 2 O morph) 680 (C tert C H-Ph) 1284 (C tert 2C-meta Ph) 10 (C tert 2C-ortho Ph) 118 (C quat Ph para/cl) 148 (C quat CCl Ph) 1676 (2 C=O) 2D NMR experiments have confirmed the signals observed and the different correlations of homo and heteronuclear MS (IE): Calc for [M] + C 18 H 24 ClNO 5 : 691 [M+H] + (m/z) = 70 (15%) [M-CH(CO 2 ] + (m/z) = 210 (100%) Elemental analysis for C 18 H 24 NO 5 Cl Calc (Found): C 585 (5860) H 650 (671) N 79 (40)% Diethyl 2-((5-dimethyl-pyrazol-1-yl)(phenyl)methyl) malonate (8): White powder mp C Rf = 069 (ether/hexane: 1/1) IR (KBr): n max /cm (C-H) 1747/1719 (C=O) 1586/1554 (C=C) 1460/1419 (C=N) 1269/1264 (C-O) 1 H NMR (00 MHz CDCl ) d: 098 (t H CH 2 CH J 71 Hz) 117 (t H CH 2 CH J 71 Hz) 221 (s 1H C H pyrazol) 225 (s 1H C 1 H pyrazol) 97(q 2H OCH 2 CH J 71 Hz) (2q 2H OCH 2 CH J 7 Hz) 49 (d 1H PhC HC 2 H J 114 Hz) 574 (s 1H H 2 pyrazol) (m 5H Ph) 778 (d 1H ph-c H J 112 Hz) 1 C NMR (755 MHz CDCl ) d: 167 (C C H pyrazol) 164/1006 (2C 2CH 2 CH ) 187 (C C 1 H pyrazol) 5752 (C tert Ph-C HC 2 H) 605 (C tert PhC HC 2 H) 6157 (2C 2CH 2 CH ) 105 (C tert C 2 H pyrazol) 12850/128/1279 (5C Ph) 170 (C quat C pyrazol) 190 (C quat Ph) 147 (C quat C 1 pyrazol) 16690/16685 (2C=O) MS (IE): Calc for [M] + C 19 H 24 N 2 O 4 : 4417 [M+H] + (m/z) = 45 (11%) 8 (100%) Elemental analysis for C 19 H 24 N 2 O 4 Calc (Found): C 6627 (6571) H 697 (580) N 81 (878)% Diethyl 2-((4-chlorophenyl)(5-dimethyl-pyrazol- 1-yl)methyl)malonate (9): White powder mp C Rf = 068 (ether/hexane: 1/1) IR (KBr): n max /cm (C-H Ph) 2674/2806 (C-H) 1747/1720 (C=O) 1592/1464 (C=C) 129/ 1256 (C-O) 1 H NMR (00 MHz CDCl ) d: (m 2H aromatic) (m 2H Ph) 45 (d 1H PhC H J 1140 Hz) 425 (q 2H CH 2 OCH J 71 Hz) 409 (d 1H C 2 H(CO 2 J 1140 Hz) 95 (m 2H CH 2 OCH ) 249 (m 2H N-C 1 H 2 pyrazole) 25 (m 2H NC 1 H 2 pyrazole) 159 (m 4H 2C 1 H 2 C 2 H 2 pyrazole) 10 (t H OCH 2 CH J 71 Hz) 10 (t H OCH 2 CH J 71 Hz) 1 C NMR (755 MHz CDCl ) d: 16697/16788

3 Vol 21 No Meskini et al S (2C=O) 15 (C quat CCl Ph) 122 (C quat Ph para/ Cl) 105 (C tert 2C ortho Ph) (C tert 2C meta Ph) 6405 (C tert C HPh) 6140 (C OCH 2 CH ester) 610 (C OCH 2 CH ester) 5650 (C tert C 2 H(CO 2 ) 4841/4688 (2C 2C 1 H 2 N pyrazole) 2284 (2C 2C 1 H 2 C 2 H 2 ) pyrazole) 191/1412 (2C 2OCH 2 CH ) MS (IE): Calc for [M] + C 18 H 24 ClNO 4 : 514 [M+H] + (m/z)=54 (18%) [M-CH(CO 2 ] + (m/z)=194 (100%) [M-pyrol] + (m/z) = 28 Elemental analysis for C 18 H 24 NO 4 Cl Calc (Found): C 6212 (6210) H 708 (728) N 18 (404)% Diethyl 2-((4-chlorophenyl)(pyrazol-1-yl)methyl) malonate (10): White crystals mp C Rf = 065 (ether/hexane; 1/1) IR (KBr): n max /cm /2985 (CH) 1748 (C=O) 1514/1595 (C=C) 1292/108 (C-O) 1 H NMR (00 MHz CDCl ) d: 75 (d 2H C H C 5 H pyrazol J 1427 Hz) (m 4H Ph J 868 Hz) 620 (t 1H pyrazol J 208 Hz) 585 (d 1H PhC H J 11 Hz) 480 (d 1 H C 2 H(CO 2 J 11 Hz) 410 (dq 2H AB OCH 2 CH J AB 142 Hz J 711 Hz) 401 (dq 2H AB OCH 2 CH J AB 142 Hz J 711 Hz) 225 (s H CH pyrazol) 220 (s H CH pyrazol) 11 (t H OCH 2 CH J 711 Hz) 104 (t H OCH 2 CH J 711 Hz) 1 C NMR (755 MHz CDCl ) d: 1666 (C=O) (C=O) (C quat pyrazol) 19 (C quat pyrazol) 157 (C quat CCl Ph) 1462 (C quat Ph para/cl) 1298 (C tert 2C meta Ph) 1287 (C tert 2C ortho Ph) (C tert C C 4 pyrazol) (C tert C 4 H pyrazol) 6175/ 6170 (C sec 2CH 2 ester) 5955 (C tert C HPh) 5745 (C tert C 2 H(CO 2 ) 187 (C OCH 2 CH ester) 175 (C OCH 2 CH ester) 166 (C CH pyrazol) 1095 (CH pyrazol) MS (IE): Calc for [M] + C 17 H 19 N 2 O 4 Cl: 505 [M+H] + (m/z) = 51 (15%) [M-CH(CO 2 ] + (m/z) = 191 (100%) [M-pyrol] + (m/z) = 28 (21%) Elemental analysis for C 18 H 24 ClNO 4 Calc (Found): C 6455 (6446) H 62 (662) N 886 (906)% Diethyl 2-((4-chlorophenyl)(piperidin-1-yl)methyl) malonate (11): White powder mp 6-65 C Rf = 065 (ether/hexane: 1/1) IR (KBr): n max /cm 1 297/290 (aromatic C-H Ph) 2797/2848 (aliphatic C-H) 1755 (C=O) 177 (C=O) 149/1452 (C=C) 112/1257 (C-O) 1 H NMR (00 MHz CDCl ) d: 105 (t H OCH 2 CH J 710 Hz) 126 (m 2H 2N(CH 2 ) 2 C H 2 J 59 Hz) 15 (t H OCH 2 CH J 710 Hz) 148 (m 4 H NC 1 H 2 C 2 H 2 ) 216 (m 2H NC 1 H 2 ) 246 (m 2H NC 1 H 2 ) 416* (d H C 2 H(CO 2 J 1210 Hz) 45* (d H PhC H J 1220 Hz); 402 (dq 2H AB OCH 2 CH J AB 11 Hz); 40 (dq 2H AB OCH 2 CH J AB 107 Hz); 71 (d 2H aromatic-ortho J 107 Hz) 72 (d 2H aromatic-meta J 109 Hz) 1 C NMR (755 MHz CDCl ) d: 14 and 18 (2C 2CH esters) 2440 (C N(CH 2 ) 2 C H 2 ) 264 (2C 2C 2 H 2 CH 2 N) 5051 (2C 2C 1 H 2 N) 5495 (C tert C 2 H(CO 2 Et) 614 and 61 (2C 2CH 2 CH ester) 695 (C tert C HPh) 1299 (C tert 2C meta/ar) (C tert 2C ortho/ar) 126 (C quat para/cl) 14 (C quat ClC) 1670 (C=O) (C=O) MS (IE): Calc for [M] + C 19 H 26 ClNO 4 : 6716 [M+H] + (m/z) = 68 (16%) [M-CH(CO 2 ] + (m/z) = 208 (100%) [M-PhCl] + (m/z) = 256 Elemental analysis for C 19 H 26 NO 4 Cl Calc (Found): C 6212 (6210) H 708 (728) N 18 (14)% Diethyl 2-((benzyl(ethyl)amino)(4-chlorophenyl) methyl)malonate (12): White crystals mp C Rf = 056 (ether/hexane: 1/1) IR (KBr): n max /cm /2985 (CH); 172 (C=O) 1594/1595 (C=C) 1248/1291 (C-O) 1 H NMR (00 MHz CDCl ) d: 10 (t H OCH 2 CH J 707 Hz); 21 (m 1H CHCH J 1290 Hz) 101 (t H OCH 2 CH J 707 Hz) 255 (m 1H CHCH J 1290 Hz) 29 (d 1H CH-Ph J 180 Hz ) 9 (d 1H CH-Ph J 180 Hz) 401 (dq 2H A-B OCH 2 CH J AB 1410 Hz J 707 Hz) 424 (d 1H C 2 H(CO 2 J 120 Hz) 40 (dq 2H AB OCH 2 CH J AB 1410 Hz J 707 Hz) 462 (d 1H ClPhC H J 120 Hz) (m 5H aromatic J 442 Hz) (m 4H PhCl J 84 Hz) 1 C NMR (755 MHz CDCl ) d: 141 (C NCH 2 CH ) 179 (C OCH 2 CH ester) 1407 (C 2OCH 2 CH ester) 5421 (C sec NCH 2 CH ) 5547 (C tert C 2 H(CO 2 ) 6175 (C tert C HPhCl) 6175/6170 (C sec 2CH 2 ester) (C tert 2C para Ph) (C-O) (C tert 2C ortho Ph) (C tert 2C ortho Ph-Cl) (C tert 2C meta Ph) 1081 (C tert 2C meta Ph-Cl) 154 (C quat Ph para/cl) 1941 (C quat CCl Ph) 1669 (C=O) MS (IE): Calc for [M] + C 2 H 28 ClNO 4 : 4175 [M+H] + (m/z)= 418 (12%) [M-CH(CO 2 ] + (m/z) = 258 (100%) [M- N(CH 2 PhC 2 H 5 )] + (m/z) = 28 Elemental analysis for C 2 H 28 ClNO 4 Calc (Found): C 6618 (655) H 671 (666) N 5 (55)% Diethyl 2-((4-chlorophenyl)(pyrrolidin-1-yl)methyl) malonate (1): White crystals mp 81-8 C Rf = 067 (ether/hexane: 1/1) IR (KBr): n max /cm /295 (CH); 1764 (C=O) 1594/1554 (C=C) 1490/146 (C=N) 100/1257 (C-O) 1 H NMR (00 MHz CDCl ) d: 104 (t H OCH 2 CH J 71 Hz) 116 (t H OCH 2 CH J 71 Hz) 220 (s H CH pyrazol) 225 (s H CH pyrazol) 40 (dq 2H AB OCH 2 CH J AB 14 Hz J 72 Hz); 412 (dq 2H AB OCH 2 CH J AB 14 Hz J 72 Hz) 484 (d 1H C 2 H(CO 2 J 11 Hz) 570 (d 1H PhC H J 11 Hz) 574 (s 1H pyrazol) (m 4H Ph J 825 Hz) 1 C NMR (755 MHz CDCl ) d: 1095 (CH pyrazol) 166 (CH -pyrazol) 175 (OCH 2 CH ester) 187 (OCH 2 CH ester) 5745 (C tert C 2 H(CO 2 ) 5955 (C tert C HPh) 6175/6170 (C sec 2CH 2 ester) 10545

4 S4 J Braz Chem Soc (C tert CH pyrazol) 1287 (C tert 2C ortho Ph) 1294 (C tert 2C meta Ph) 1425 (C quat Ph para/cl) 189 (C quat CCl Ph) 19 (C quat pyrazol) (C quat pyrazol) (C=O) (C=O) MS (IE): Calc for [M] + C 19 H 2 ClN 2 O 4 : 781 [M+H] + (m/z) = 79 (17%) [M-CH(CO 2 ] + (m/z) = 219 (100%) [M-pyrazol)] + (m/z) = 28 Elemental analysis for C 19 H 2 N 2 O 4 Cl Calc (Found): C 601 (604) H 608 (605) N 740 (769)% Diethyl 2-((-methoxyphenyl)(piperidin-1-yl)methyl) malonate (14): White crystals mp 98 C Rf = 070 (ether/hexane: 2/1) IR (KBr): n max /cm (C=O) 120/1277 (C-O) 1 H NMR (00 MHz CDCl ) d: 10 (t H OCH 2 CH J 90 Hz) 158 (t H OCH 2 CH J 90 Hz) (m 2H NC 1 H 2 ) (m 2H NC 1 H 2 ) 419 (dq 2H AB OCH 2 CH J AB 10 Hz) 407 (s H CH OPh) 48 (dq 2H AB OCH 2 CH J AB 10 Hz); 47 (d H PhC H J 10 Hz); 70 (d 2H Ph) 725 (d 2H Ph) 1 C NMR (755 MHz CDCl ) d: 14 and 145 (2C 2CH ester) 2210 (C N(CH 2 ) 2 C H 2 ) 248 (2C 2C 2 H 2 CH 2 N) 501 (2C 2C 1 H 2 N) 541 (C tert C 2 H(CO 2 Et) 58 (C tert C HPh) 605 (CH OPh) 619 and 62 (2C 2CH 2 CH ester) 1196 (C tert ) 105 (C tert ) 159 (C quat CH OC) 172 (C quat ) 1751 (C=O) 1767 (C=O) MS (IE): Calc for [M] + C 20 H 29 NO 5 : 656 [M+H] + (m/z) = 64 (10%) [M-CH(CO 2 ] + (m/z) = 204 (100%) Elemental analysis for C 20 H 29 NO 5 Calc (Found): C 6609 (6612) H 804 (814) N 85 (89)% Diethyl 2-((4-methoxyphenyl)(piperidin-1-yl)methyl) malonate (15): White crystals mp 101 C Rf = 071 (ether/hexane: 2/1) IR (KBr): n max /cm /295 (CH); 1764 (C=O) 1280/1277 (C-O) 1 H NMR (00 MHz CDCl ) d: 15 (t H OCH 2 CH J 70 Hz) 151 (t H OCH 2 CH J 70 Hz) 245 (m 2H NC 1 H 2 ) 276 (m 2H NC 1 H 2 ) 405 (s 1H CH O) 45 (dq 2H AB OCH 2 CH J AB 10 Hz) 448 (dq 2H AB OCH 2 CH J AB 11 Hz) 481 (d H PhC H J 10 Hz); (m 4H Ph) 1 C NMR (755 MHz CDCl ) d: 150 and 148 (2C 2CH ester) 2210 (C N(CH 2 ) 2 C H 2 ) 252 (2C 2C 2 H 2 CH 2 N) 4861 (2C 2C 1 H 2 N) 5615 (C tert C 2 H(CO 2 Et) 58 (C tert C HPh) 614 and 61 (2C 2CH 2 CH ester) 1110 (C tert ) 1299 (C tert ) 126 (C quat) 151 (C quat CH OC) (C=O) (C=O) MS (IE): Calc for [M] + C 20 H 29 NO 5 : 657 [M+H] + (m/z) = 64 (19%) [M-CH(CO 2 ] + (m/z) = 204 (100%) Elemental analysis for C 20 H 29 NO 5 Calc (Found): C 6609 (6592) H 804 (802) N 85 (68)% Table S1 Bond lengths (Å) and angles (deg) for 9 O(1)-C() 1201(2) O(4)-C(7) 1458(2) O(2)-C() 11(2) N(1)-C(15) 156(2) O(2)-C(4) 1459(2) N(1)-N(2) 166(2) O()-C(6) 1202(2) N(1)-C(1) 146(2) O(4)-C(6) 15(2) N(2)-C(17) 11(2) O(1)-C()-O(2) 12478(15) N(1)-C(1)-C(9) 1124(1) O(1)-C()-C(2) 12424(16) N(1)-C(1)-C(2) 10800(14) O(2)-C()-C(2) 11097(14) N(1)-C(15)-C(16) 1057(16) O(2)-C(4)-C(5) 10659(14) N(1)-C(15)-C(18) 12259(15) O()-C(6)-O(4) 12497(17) N(2)-C(17)-C(16) 11085(15) O()-C(6)-C(2) 12402(17) N(2)-C(17)-C(19) 11980(16) O(4)-C(6)-C(2) 11099(15) N(2)-N(1)-C(1) 11957(1)

5 Vol 21 No Meskini et al S5 Table S2 Torsion angles [deg] for (9) N(1)-C(1)-C(2)-C() 17859(12) C(1)-C(2)-C(6)-O() 99(2) N(1)-C(1)-C(2)-C(6) 6069(16) C(1)-N(1)-C(15)-C(16) 17555(16) N(1)-N(2)-C(17)-C(16) 07(18) C(1)-N(1)-N(2)-C(17) 17598(14) N(1)-N(2)-C(17)-C(19) 17940(15) C(1)-N(1)-C(15)-C(18) 54() N(1)-C(1)-C(9)-C(14) 12896(16) C(1)-C(2)-C(6)-O(4) 14176(14) N(1)-C(1)-C(9)-C(10) 512(2) C()-O(2)-C(4)-C(5) 1747(15) N(1)-C(15)-C(16)-C(17) 049(19) C()-C(2)-C(6)-O() 790(2) N(2)-N(1)-C(1)-C(2) 414(19) C()-C(2)-C(6)-O(4) 990(16) N(2)-N(1)-C(1)-C(9) 805(18) C(6)-O(4)-C(7)-C(8) 819(2) N(2)-N(1)-C(15)-C(16) 077(19) C(7)-O(4)-C(6)-O() 11() N(2)-N(1)-C(15)-C(18) 17986(16) C(7)-O(4)-C(6)-C(2) 1794(14) Table S Electrostatic-bond parameters for 9 (Å ) D-XA d(d-x) d(xa) d(da) <(D-X A) C12 Cl1 N2 174(2) 11(4) 484(7) 1185(4) Figure S1 1 H NMR (00 MHz) spectrum of compound 6 in CDCl

6 S6 J Braz Chem Soc Figure S2 1 H NMR (00 MHz) spectrum of compound 6 in CDCl expanded at 45-10ppm Figure S 1 C NMR (75 MHz) spectrum of compound 6 in CDCl

7 Vol 21 No Meskini et al S7 Figure S4 HETCOR of compound 6 in CDCl Figure S5 COSY of compound 6 in CDCl

8 S8 J Braz Chem Soc Figure S6 1 H NMR (00 MHz) spectrum of compound 7 in CDCl Figure S7 1 C NMR (75 MHz) spectrum of compound 7 in CDCl

9 Vol 21 No Meskini et al S9 Figure S8 COSY of compound 7 in CDCl Figure S9 HETCOSY of compound 7 in CDCl

10 S10 J Braz Chem Soc Figure S10 COSY of compound 7 in CDCl Figure S11 1 H NMR (00 MHz) spectrum of compound 9 in CDCl

11 Vol 21 No Meskini et al S11 Figure S12 1 C NMR (755 MHz) spectrum of compound 9 in CDCl Figure S1 COSY of compound 9 in CDCl

12 S12 Figure S14 1H NMR (00 MHz) spectrum of compound 9 in CDCl expanded at 45-10ppm Figure S15 1H NMR (00 MHz) spectrum of compound 10 in CDCl J Braz Chem Soc

13 Vol 21 No Meskini et al S1 Figure S16 1 C NMR (755 MHz) spectrum of compound 10 in CDCl Figure S17 COSY of compound 10 in CDCl

14 S14 J Braz Chem Soc Figure S18 HETCOSY of compound 10 in CDCl Figure S19 1 H NMR (00 MHz) spectrum of compound 11 in CDCl

15 Vol 21 No Meskini et al S15 Figure S20 1 C NMR (755 MHz) spectrum of compound 11 in CDCl Figure S21 COSY of compound 11 in CDCl

16 S16 J Braz Chem Soc Figure S22 HETCOSY of compound 11 in CDCl Figure S2 1 H NMR (00 MHz) spectrum of compound 12 in CDCl

17 Vol 21 No Meskini et al S17 Figure S24 1 C NMR (755 MHz) spectrum of compound 12 in CDCl Figure S25 COSY of compound 12 in CDCl

18 S18 J Braz Chem Soc Figure S26 COSY of compound 12 in CDCl