-
S1
Supporting Information
One-step Barton decarboxylation by micellar catalysis – application to the synthesis of maleimide derivatives
Floriane Mangin,a Estelle Banaszak-Léonarda and Christophe Lena,b*
aSorbonne Universités, Université de Technologie de Compiègne, Ecole Supérieure de Chimie Organique et Minérale, EA 4297 Transformations Intégrées de la Matière Renouvelable, Centre de Recherche Royallieu, CS
60319, F-60203 Compiègne cedex, France. Fax: +33 (0)3 44 97 15 91; Tel: +33 (0)3 44 23 88 28;
bDepartment of Chemistry, University of Hull, Hull HU6 7RX, England.E-mail: [email protected]
Table of ContentsGeneral information S1
General procedure for the Barton decarboxylation S1
General procedure for maleimide formation S1
Spectral data of all compounds S2 – S6
NMR spectra of all compounds S7 – S23
General informationAll products were purchased either from Acros or Sigma Aldrich depending on their availability and were used without further purification. All solvents were purchased from Carlo Erba. Reactions were performed with an ultrasonic probe (Bioblock Scientific, Vibra cell 75042) and monitored by TLC (Kieselgel 60F254 MERCK aluminium sheet) with detection by UV light and/or phosphomolybdic acid solution and by HPLC (Shimazu). Flash column chromatography was performed on an automatic Grace apparatus, using 40 g connected silica gel cartridges. 1H and 13C NMR spectra were recorded on a 400 MHz Bruker UltraShield 400 MHz/54 mm Ultra long hold. Chemical shifts (δ) are quoted in ppm and are referenced to TMS as an internal standard. Coupling constants (J) are quoted in Hz. IR spectra were recorded on a Jasco FT/IR-4100 ATR.
General procedure for the Barton decarboxylationIn a 100 mL Beaker containing a Brij®30 aqueous solution (300 mg in 30 mL), 2-mercaptopyridine-N-oxide (150 mg, 1.2 mmol), DCC (250 mg, 1.2 mmol), N-phenylmaleimide (268 mg, 1.5 mmol) and carboxylic acid (1.03 mmol) were introduced. The mixture was sonicated 20 min in an ice bath (the ultrasonic probe was placed at 1cm from the bottom of the beaker to ensure a homogenous dispersion). The crude mixture was lyophilized and the residue was purified on flash chromatography (Cyclohexane/EtOAc 1/0 to 7/3).
General procedure for maleimide formationIn a 50 mL round bottom flask containing 1-phenylpyridin-2-ylthiopyrrolidine-2,5-dione (1 mmol) product in CH2Cl2 (10 mL) was added m-CPBA (246 mg, 10 mmol) and the mixture is stirred for 10 min. at 0°C. Then saturated NaHCO3 solution (30 mL) was added and the crude product extracted with CH2Cl2 (30 mL). After the evaporation of the solvent, toluene (20 mL) was added and the media was heated under reflux for 1h. Toluene was evaporated and the crude mixture was purified on flash chromatography (Cyclohexane/EtOAc 1/0 to 7/3).
Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2015
mailto:[email protected]
-
S2
3-Pentyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (1)
NS
O
O
N
Following general procedure for Barton decarboxylation, white solid (218 mg, 60% yield).mp: 77-79°C1H NMR (400 MHz, CDCl3) δ ppm: 0.92 (t, J = 7.1 Hz, 3H, CH3), 1.34-1.37 (m, 4H, CH2), 1.53-1.60 (m, 2H, CH2), 1.78-1.87 (m, 1H, CH2), 2.04-2.12 (m, 1H, CH2), 3.23 (dt, J = 8.6 and 5.2 Hz, 1H, CHCO), 3.92 (d, J = 5.6 Hz, 1H, CHS), 7.02 (ddd, J = 7.4, 5.0 and 1.0 Hz, 1H, CH), 7.22 (d, J = 8.1 Hz, 1H, CH), 7.34-7.42 (m, 3H, CHar), 7.46-7.55 (m, 3H, CHar), 8.29 (ddd, J = 5.0, 1.8 and 1.0 Hz, 1H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 14.0 (CH3), 22.4 (CH2), 26.1 (CH2), 30.7 (CH2), 31.6 (CH2), 46.9 (CH), 47.2 (CHS), 120.2 (CH), 122.1 (CH), 126.4 (2 CHPh), 128.5 (CHPh), 129.1 (2 CHPh), 132.5 (CPhN), 136.6 (CH), 149.0 (CHN), 156.1 (CS), 174.4 (COCHS), 177.4 (CO)νmax/cm-1: 1707 (C=O), 1389 (CH), 1173 (C-N),HRMS (ESI): found 355.1480; calculated 355.1480 for C20H23N2O2S
3-Hexyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (2)
NS
O
O
N
Following general procedure for Barton decarboxylation, colourless wax (235 mg, 62% yield).1H NMR (400 MHz, CDCl3) δ ppm: 0.89 (t, J = 7.0 Hz, 3H, CH3), 1.26-1.39 (m, 6H, CH2), 1.55 (quin, J = 7.5 Hz, 2H, CH2), 1.77-1.87 (m, 1H, CH2), 2.04-2.13 (m, 1H, CH2), 3.24 (dt, J = 8.7 and 5.3 Hz, 1H, CHCO), 3.90 (d, J = 5.7 Hz, 1H, CHS), 7.01 (ddd, J = 7.4, 5.0 and 1.0 Hz, 1H, CH), 7.21 (d, J = 8.1 Hz, 1H, CH), 7.34-7.42 (m, 3H, CHar), 7.46-7.54 (m, 3H, CHar), 8.29 (ddd, J = 4.9, 1.7 and 0.9 Hz, 1H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 14.0 (CH3), 22.5 (CH2), 26.4 (CH2), 29.1 (CH2), 30.7 (CH2), 31.5 (CH2), 46.9 (CH), 47.2 (CHS), 120.2 (CH), 122.1 (CH), 126.4 (2 CHPh), 128.5 (CHPh), 129.1 (2 CHPh), 132.5 (CPhN), 136.6 (CH), 148.9 (CHN), 156.0 (CS), 174.4 (COCHS), 177.3 (CO)νmax/cm-1: 1715 (C=O), 1381 (CH), 1183 (C-N),HRMS (ESI): found 369.1635; calculated 369.1632 for C21H25N2O2S
3-Heptyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (3)
Following general procedure for Barton decarboxylation, colourless oil (228 mg, 58% yield).1H NMR (400 MHz, CDCl3) δ ppm: 0.88 (t, J = 6.9 Hz, 3H, CH3), 1.26-1.37 (m, 8H, CH2), 1.55 (quin, J = 7.5 Hz, 2H, CH2), 1.77-1.87 (m, 1H, CH2), 2.04-2.12 (m, 1H, CH2), 3.23 (dt, J = 8.7 and 5.2 Hz, 1H, CHCO), 3.93 (d, J = 5.6 Hz, 1H, CHS), 7.02 (ddd, J = 7.4, 5.0 and 1.0 Hz, 1H, CH), 7.23 (d, J = 8.1 Hz, 1H, CH), 7.33-7.41 (m, 3H, CHar), 7.45-7.55 (m, 3H, CHar), 8.29 (ddd, J = 5.0, 1.7 and 1.0 Hz, 1H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 14.0 (CH3), 22.6 (CH2), 26.5 (CH2), 29.0 (CH2), 29.4 (CH2), 30.7 (CH2), 31.7 (CH2), 46.9 (CH), 47.1 (CHS), 120.3 (CH), 122.2 (CH), 126.4 (2 CHPh), 128.5 (CHPh), 129.1 (2 CHPh), 132.5 (CPhN), 136.7 (CH), 148.9 (CHN), 156.0 (CS), 174.4 (COCHS), 177.3 (CO)νmax/cm-1: 1715 (C=O), 1380 (CH), 1184 (C-N),HRMS (ESI): found 383.1788; calculated 383.1793 for C22H27N2O2S
NS
O
O
N
-
S3
3-Nonyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (4)
Following general procedure for Barton decarboxylation, white solid (235 mg, 54% yield).mp: 56-57°C1H NMR (400 MHz, CDCl3) δ ppm: 0.88 (t, J = 6.9 Hz, 3H, CH3), 1.26-1.36 (m, 12H, CH2), 1.56 (quin, J = 7.4 Hz, 2H, CH2), 1.78-1.87 (m, 1H, CH2), 2.04-2.12 (m, 1H, CH2), 3.23 (dt, J = 8.8 and 5.1 Hz, 1H, CHCO), 3.92 (d, J = 5.6 Hz, 1H, CHS), 7.02 (dd, J = 6.7 and 5.0 Hz, 1H, CH), 7.23 (d, J = 8.1 Hz, 1H, CH), 7.35-7.41 (m, 3H, CHar), 7.46-7.55 (m, 3H, CHar), 8.29 (d, J = 4.5 Hz, 1H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 14.1 (CH3), 22.6 (CH2), 26.5 (CH2), 29.2 (CH2), 29.3 (CH2), 29.4 (CH2), 29.5 (CH2), 30.8 (CH2), 31.8 (CH2), 46.9 (CH), 47.2 (CHS), 120.3 (CH), 122.2 (CH), 126.4 (2 CHPh), 128.5 (CHPh), 129.1 (2 CHPh), 132.5 (CPhN), 136.7 (CH), 149.0 (CHN), 156.0 (CS), 174.4 (COCHS), 177.3 (CO)νmax/cm-1: 1716 (C=O), 1386 (CH), 1180 (C-N),HRMS (ESI): found 411.2102; calculated 411.2106 for C24H31N2O2S
1-Phenyl-3-(pyridin-2-ylthio)-4-undecylpyrrolidine-2,5-dione (5)
Following general procedure for Barton decarboxylation, white solid (258 mg, 57% yield).mp: 62-65°C1H NMR (400 MHz, CDCl3) δ ppm: 0.88 (t, J = 6.9 Hz, 3H, CH3), 1.26 (bs, 16H, CH2), 1.55 (quin, J = 7.5 Hz, 2H, CH2), 1.77-1.87 (m, 1H, CH2), 2.03-2.12 (m, 1H, CH2), 3.23 (dt, J = 8.7 and 5.2 Hz, 1H, CHCO), 3.92 (d, J = 5.7 Hz, 1H, CHS), 7.01 (ddd, J = 7.4, 5.0 and 1.0 Hz, 1H, CH), 7.22 (dt, J = 8.1 and 0.9 Hz, 1H, CH), 7.34-7.41 (m, 3H, CHar), 7.45-7.54 (m, 3H, CHar), 8.28 (ddd, J = 5.0, 1.8 and 1.0 Hz, 1H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 14.1 (CH3), 22.6 (CH2), 26.4 (CH2), 29.3 (CH2), 29.3 (CH2), 29.4 (CH2), 29.5 (CH2), 29.5 (2 CH2), 30.7 (CH2), 31.8 (CH2), 46.9 (CH), 47.1 (CHS), 120.2 (CH), 122.1 (CH), 126.4 (2 CHPh), 128.4 (CHPh), 129.0 (2 CHPh), 132.5 (CPhN), 136.6 (CH), 148.9 (CHN), 156.0 (CS), 174.3 (COCHS), 177.3 (CO)νmax/cm-1: 1714 (C=O), 1388 (CH), 1182 (C-N),HRMS (ESI): found 439.2418; calculated 439.2419 for C26H35N2O2S
1-Phenyl-3-(pyridin-2-ylthio)-4-tetradecylpyrrolidine-2,5-dione (6)
Following general procedure for Barton decarboxylation, white solid (301 mg, 61% yield).mp: 72-74°C1H NMR (400 MHz, CDCl3) δ ppm: 0.88 (t, J = 6.8 Hz, 3H, CH3), 1.26 (bs, 22H, CH2), 1.55 (quin, J = 7.5 Hz, 2H, CH2), 1.77-1.87 (m, 1H, CH2), 2.04-2.12 (m, 1H, CH2), 3.23 (dt, J = 8.7 and 5.1 Hz, 1H, CHCO), 3.91 (d, J = 5.6 Hz, 1H, CHS), 7.02 (dd, J = 6.7 and 5.6 Hz, 1H, CH), 7.22 (d, J = 8.1 Hz, 1H, CH), 7.35-7.41 (m, 3H, CHar), 7.46-7.55 (m, 3H, CHar), 8.29 (d, J = 4.9 Hz, 1H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 14.1 (CH3), 22.7 (CH2), 26.5 (CH2), 29.3 (CH2), 29.3 (CH2), 29.4 (CH2), 29.5 (CH2), 29.6 (CH2), 29.6 (2 CH2), 29.7 (CH2), 29.7 (CH2), 30.8 (CH2), 31.9 (CH2), 46.9 (CH), 47.1 (CHS), 120.2 (CH), 122.1 (CH), 126.4 (2 CHPh), 128.4 (CHPh), 129.1 (2 CHPh), 132.5 (CPhN), 136.7 (CH), 148.9 (CHN), 156.0 (CS), 174.4 (COCHS), 177.3 (CO)νmax/cm-1: 1704 (C=O), 1391 (CH), 1174 (C-N),HRMS (ESI): found 481.2891; calculated 481.2889 for C29H41N2O2S
NS
O
O
N
5
NS
O
O
N
7
NS
O
O
N
10
-
S4
3-Pentadecyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (7)
Following general procedure for Barton decarboxylation, white solid (336 mg, 66% yield).mp: 68-71°C1H NMR (400 MHz, CDCl3) δ ppm: 0.80 (t, J = 6.9 Hz, 3H, CH3), 1.18-1.36 (m, 24H, CH2), 1.50 (quin, J = 7.4 Hz, 2H, CH2), 1.70-1.77 (m, 1H, CH2), 2.96-2.03 (m, 1H, CH2), 3.13 (dt, J = 8.8 and 5.1 Hz, 1H, CHCO), 3.86 (d, J = 5.6 Hz, 1H, CHS), 6.95 (dd, J = 6.7 and 5.0 Hz, 1H, CH), 7.17 (d, J = 8.1 Hz, 1H, CH), 7.27-7.34 (m, 3H, CHar), 7.39-7.49 (m, 3H, CHar), 8.22 (d, J = 4.5 Hz, 1H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 14.1 (CH3), 22.7 (CH2), 26.5 (CH2), 29.4 (CH2), 29.4 (CH2), 29.5 (CH2), 29.6 (CH2), 29.6 (CH2), 29.6 (CH2), 29.7 (CH2), 30.7 (CH2), 31.9 (CH2), 46.9 (CH), 47.2 (CHS), 120.3 (CH), 122.2 (CH), 126.4 (2 CHPh), 128.5 (CHPh), 129.1 (2 CHPh), 132.5 (CPhN), 136.8 (CH), 148.9 (CHN), 156.0 (CS), 174.4 (COCHS), 177.3 (CO)νmax/cm-1: 1708 (C=O), 1387 (CH), 1173 (C-N),HRMS (ESI): found 495.3047; calculated 495.3045 for C30H43N2O2S
3-Heptadecyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (8)
Following general procedure for Barton decarboxylation, white solid (296 mg, 55% yield).mp: 85-86°C1H NMR (400 MHz, CDCl3) δ ppm: 0.88 (t, J = 6.9 Hz, 3H, CH3), 1.26 (bs, 28H, CH2), 1.56 (quin, J = 7.5 Hz, 2H, CH2), 1.78-1.87 (m, 1H, CH2), 2.04-2.13 (m, 1H, CH2), 3.23 (dt, J = 8.7 and 5.2 Hz, 1H, CHCO), 3.95 (d, J = 5.6 Hz, 1H, CHS), 7.03 (ddd, J = 7.4, 5.0 and 1.0 Hz, 1H, CH), 7.24 (dt, J = 8.1 and 0.9 Hz, 1H, CH), 7.34-7.42 (m, 3H, CHar), 7.46-7.56 (m, 3H, CHar), 8.30 (ddd, J = 5.0, 1.8 and 1.0 Hz, 1H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 14.1 (CH3), 22.7 (CH2), 26.5 (CH2), 29.3 (CH2), 29.3 (CH2), 29.4 (CH2), 29.5 (CH2), 29.6 (CH2), 29.7 (2 CH2), 29.7 (5 CH2), 30.8 (CH2), 31.9 (CH2), 46.9 (CH), 47.2 (CHS), 120.3 (CH), 122.3 (CH), 126.4 (2 CHPh), 128.5 (CHPh), 129.1 (2 CHPh), 132.5 (CPhN), 136.8 (CH), 148.9 (CHN), 156.0 (CS), 174.4 (COCHS), 177.3 (CO)νmax/cm-1: 1708 (C=O), 1388 (CH), 1169 (C-N),HRMS (ESI): found 523.3363; calculated 523.3359 for C32H47N2O2S and found 545.3198; calculated 545.3177 for C32H46N2O2SNa
(Z)-3-(Heptadec-8-en-1-yl)-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (9)
Following general procedure for Barton decarboxylation, colourless oil (321 mg, 60% yield).1H NMR (400 MHz, CDCl3) δ ppm: 0.88 (t, J = 6.9 Hz, 3H, CH3), 1.27-1.31 (m, 22H, CH2), 1.56 (quin, J = 7.4 Hz, 2H, CH2), 1.77-1.87 (m, 1H, CH2), 2.01-2.05 (m, 1H, CH2), 3.23 (dt, J = 8.7 and 5.2 Hz, 1H, CHCO), 3.91 (d, J = 5.7 Hz, 1H, CHS), 5.35 (dt, J = 5.7 and 3.5 Hz, 2H, CH), 7.01 (ddd, J = 7.4, 5.0 and 1.0 Hz, 1H, CH), 7.23 (dt, J = 8.1 and 0.9 Hz, 1H, CH), 7.35-7.41 (m, 3H, CHar), 7.46-7.55 (m, 3H, CHar), 8.29 (ddd, J = 4.9, 1.8 and 0.9 Hz, 1H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 14.1 (CH3), 22.7 (CH2), 26.5 (CH2), 27.1 (CH2), 27.2 (CH2), 29.1 (CH2), 29.2 (CH2), 29.3 (2 CH2), 29.4 (CH2), 29.5 (CH2), 29.7 (CH2), 29.7 (CH2), 30.7 (CH2), 31.9 (CH2), 46.9 (CH), 47.1 (CHS), 120.2 (CH), 122.1 (CH), 126.4 (2 CHPh), 128.4 (CHPh), 129.1 (2 CHPh), 129.7 (CH), 130.0 (CH), 132.5 (CPhN), 136.6 (CH), 149.0 (CHN), 156.0 (CS), 174.3 (COCHS), 177.3 (CO)νmax/cm-1: 1717 (C=O), 1384 (CH), 1179 (C-N),HRMS (ESI): found 521.3221; calculated 521.3202 for C32H45N2O2S
NS
O
O
N
11
NS
O
O
N
13
NS
O
O
N
5
5
-
S5
3-((8Z,11Z)-Heptadeca-8,11-dien-1-yl)-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (10)
Following general procedure for Barton decarboxylation, colourless oil (327 mg, 61% yield).1H NMR (400 MHz, CDCl3) δ ppm: 0.89 (t, J = 7.0 Hz, 3H, CH3), 1.29-1.37 (m, 14H, CH2), 1.55 (quin, J = 7.2 Hz, 2H, CH2), 1.76-1.86 (m, 1H, CH2), 2.06 (q, J = 6.8 Hz, 5H, CH2), 2.78 (t, J = 6.3 Hz, 2H, CH2), 3.23 (dt, J = 8.7 and 5.2 Hz, 1H, CHCO), 3.89 (d, J = 5.7 Hz, 1H, CHS), 5.30-5.43 (m, 4H, CH), 6.98 (ddd, J = 7.3, 5.0 and 0.8 Hz, 1H, CH), 7.19 (d, J = 8.1 Hz, 1H, CH), 7.34-7.40 (m, 3H, CHar), 7.44-7.52 (m, 3H, CHar), 8.27 (ddd, J = 4.9, 1.7 and 1.0 Hz, 1H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 14.0 (CH3), 22.4 (CH2), 25.5 (CH2), 26.4 (CH2), 27.1 (2 CH2), 29.0 (CH2), 29.1 (CH2), 29.2 (CH2), 29.3 (CH2), 29.5 (CH2), 30.6 (CH2), 31.4 (CH2), 46.8 (CH), 47.0 (CHS), 120.1 (CH), 121.9 (CH), 126.3 (2 CHPh), 127.8 (CH), 127.9 (CH), 128.3 (CHPh), 128.9 (2 CHPh), 129.9 (CH), 130.1 (CH), 132.5 (CPhN), 136.5 (CH), 148.9 (CHN), 155.9 (CS), 174.2 (COCHS), 177.2 (CO)νmax/cm-1: 1717 (C=O), 1382 (CH), 1179 (C-N),HRMS (ESI): found 519.3052; calculated 519.3046 for C32H43N2O2S
3-Pentyl-1-phenyl-1H-pyrrole-2,5-dione (11)
Following general procedure for maleimide formation, white solid, (242 mg, quantitative yield).mp: 72-73°C1H NMR (400 MHz, CDCl3) δ ppm: 0.93 (t, J = 7.1 Hz, 3H, CH3), 1.33-1.42 (m, 4H, CH2), 1.63-1.70 (m, 2H, CH2), 2.52 (dt, J = 7.7 and 1.7 Hz, 2H, CH2), 6.43 (t, J = 1.2 Hz, 1H, CH), 7.33-7.36 (m, 3H, CHar), 7.43-7.48 (m, 2H, CHar)13C NMR (100 MHz, CDCl3) δ ppm: 13.9 (CH3), 22.3 (CH2), 25.5 (CH2), 26.8 (CH2), 31.3 (CH2), 125.9 (2 CHPh), 126.3 (CHCO), 127.6 (CHPh), 129.0 (2 CHPh), 131.6 (CPhN), 150.4 (COCCH2), 169.7 (CO), 170.4 (COCCH2)νmax/cm-1: 1707 (C=O), 1388 (CH), 1179 (C-N)HRMS (ESI): found 244.1340, calculated 244.1338 for C15H18NO2
NS
O
O
N
5
4
O
O
N
-
S6
3,4-Dipentyl-1-phenyl-3-(pyridin-2-ylthio)pyrrolidine-2,5-dione ((±)12a and (±)12b)
In a 100 mL Beaker containing a Brij®30 aqueous solution (300 mg in 30 mL), 2-mercaptopyridine-N-oxide (225 mg, 1.8 mmol), DCC (375 mg, 1.8 mmol), 11 (243 mg, 1 mmol) and caproic acid (174 mg,1.5 mmol) were introduced. The mixture was sonicated 20 min in an ice bath (the ultrasonic probe was placed at 1cm from the bottom of the beaker to ensure a homogenous dispersion). The crude mixture was lyophilized and the residue was purified on flash chromatography (Cyclohexane/EtOAc 1/0 to 7/3).Pale yellow oil (200 mg, 47% yield).1H NMR (400 MHz, CDCl3) δ ppm: 0.85-0.93 (m, 6H, CH3), 1.27-1.38 (m, 9H, CH2), 1.56-1.77 (m, 4H, CH2), 1.82-2.16 (m, 3H, CH2), 2.96 (dd, J = 7.1 and 5.7 Hz, 0.6H, CH), 3.65 (t, J = 6.8 Hz, 0.4H, CH), 6.99 (ddd, J = 7.4, 6.2, and 5.0 Hz, 1H, CH), 7.17-7.22 (m, 1H, CH), 7.26-7.29 (m, 1H, CH), 7.32-7.52 (m, 5H, CHPh), 8.19 (ddd, J = 5.0, 1.8 and 0.9 Hz, 0.6H, CH), 8.30 (ddd, J = 5.0, 1.8 and 0.9 Hz, 0.4H, CH)13C NMR (100 MHz, CDCl3) δ ppm: 13.9 (CH3), 14.0 (CH3), 22.2 (CH2), 22.3 (CH2), 22.3 (CH2), 22.3 (CH2), 24.0 (CH2), 24.3 (CH2), 28.0 (CH2), 28.1 (CH2), 28.7 (CH2), 31.7 (2 CH2), 31.7 (CH2), 31.8 (CH2), 33.9 (CH2CH), 38.4 (CH2CS), 47.8 (CHCO), 48.1 (CHCO), 56.9 (CSCO), 59.0 (CSCO), 120.0 (CH), 120.2 (CH), 122.0 (CH), 122.1 (CH), 126.3 (2 CHPh), 126.4 (2 CHPh), 128.1 (CHPh), 128.3 (CHPh), 128.9 (2 CHPh), 129.0 (2 CHPh), 132.6 (CPhN), 136.4 (CH), 136.4 (CH), 148.7 (CHN), 148.9 (CHN), 156.9 (CS), 157.4 (CS), 176.2 (COCS), 176.9 (COCS), 177.1 (COCH), 177.5 (COCH)νmax/cm-1: 1714 (C=O), 1387 (CH), 1182 (C-N),HRMS (ESI): found 447.2086, calculated 447.2082 for C25H32N2O2SNa
3,4-Dipentyl-1-phenyl-1H-pyrrole-2,5-dione (13)
Following general procedure for maleimide formation, pale yellow oil (310 mg, quantitative yield).1H NMR (400 MHz, CDCl3) δ ppm: 0.92 (t, J = 7.1 Hz, 6H, CH3), 1.34-1.39 (m, 8H, CH2), 1.58-1.61 (m, 4H, CH2), 2.46 (t, J = 7.7 Hz, 4H, CH2), 7.31-7.38 (m, 3H, CHar), 7.42-7.46 (m, 2H, CHar)13C NMR (100 MHz, CDCl3) δ ppm: 13.9 (CH3), 22.4 (CH2), 23.8 (CH2), 28.3 (CH2), 31.8 (CH2), 125.7 (2 CHPh), 127.2 (CHPh), 129.0 (2 CHPh), 132.0 (CPhN), 141.2 (C=C), 170.8 (CO)νmax/cm-1: 1709 (C=O), 1305 (CH), 1198 (C-N)HRMS (ESI): found 314.2120, calculated 314.2106 for C20H28NO2
CC
N
O
O
CC
N
O
OH H
S S
N N
(±)12a (±)12b
N
O
O
-
S7
ppm (t1)102030405060708090100110120130140150160170180190
177.
363
174.
395
156.
040
149.
013
136.
625
132.
526
129.
091
128.
467
126.
403
122.
079
120.
226
77.3
1777
.202
77.0
0076
.682
47.1
8246
.905
31.5
9730
.709
26.1
4922
.403
13.9
76
NS
O
O
N
3-pentyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (1)
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.30
18.
298
8.29
68.
294
8.28
88.
286
8.28
48.
282
7.55
47.
550
7.53
47.
531
7.51
57.
511
7.50
07.
482
7.46
77.
463
7.45
77.
415
7.41
27.
409
7.39
37.
367
7.36
47.
346
7.34
37.
236
7.21
67.
037
7.03
57.
025
7.02
27.
019
7.01
67.
006
7.00
4
3.93
33.
918
3.25
73.
244
3.23
63.
231
3.22
23.
209
2.12
42.
111
2.10
32.
090
2.07
02.
065
2.05
32.
048
2.03
5
1.87
11.
854
1.84
91.
832
1.81
71.
811
1.79
71.
776
1.59
91.
582
1.57
51.
564
1.54
61.
525
1.36
81.
360
1.35
01.
342
0.92
00.
902
0.88
4
1.00
3.063.001.011.02
3.15
4.002.15
1.19
1.09
1.02
1.01
NS
O
O
N
-
S8
ppm (t2)3.003.103.203.303.403.503.603.703.803.904.00
8.00
8.10
8.20
8.30
8.40
8.50
8.60
8.70
ppm (t1)
NOESY
-
S9
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.29
28.
281
7.54
67.
542
7.52
67.
523
7.50
87.
503
7.49
67.
482
7.46
77.
463
7.45
77.
412
7.40
97.
393
7.37
57.
368
7.36
47.
347
7.26
07.
228
7.20
87.
029
7.01
47.
011
7.00
86.
998
6.99
6
6.84
73.
908
3.89
43.
260
3.24
73.
238
3.23
33.
225
3.21
1
2.12
52.
112
2.10
42.
091
2.08
42.
078
2.07
12.
067
2.06
22.
054
2.04
92.
043
2.03
7
1.86
91.
852
1.84
71.
830
1.81
51.
809
1.79
41.
774
1.57
31.
554
1.53
61.
515
1.31
81.
311
1.30
10.
904
0.88
60.
868
1.00
3.293.220.981.030.12
3.31
6.22
2.23
1.19
1.04
1.01
1.04
NS
O
O
N
ppm (t1)102030405060708090100110120130140150160170180190
177.
338
174.
370
156.
017
148.
983
136.
619
134.
159
132.
518
129.
069
128.
445
126.
392
122.
070
120.
213
77.3
1877
.000
76.6
82
47.1
4946
.891
31.5
2630
.727
29.0
6926
.423
22.5
02
14.0
11
NS
O
O
N
3-hexyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (2)
-
S10
ppm (t1)102030405060708090100110120130140150160170180190
177.
317
174.
372
155.
973
148.
908
136.
709
134.
158
132.
498
129.
069
128.
452
126.
390
126.
024
122.
151
120.
257
77.3
1877
.000
76.6
82
47.1
3346
.893
31.6
8530
.718
29.3
6729
.003
26.4
7322
.569
14.0
44
SN
O
O
N
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.30
08.
296
8.28
88.
285
7.55
37.
548
7.53
37.
530
7.51
47.
510
7.49
97.
481
7.47
17.
466
7.46
27.
411
7.39
27.
373
7.36
67.
363
7.35
77.
349
7.34
57.
260
7.23
57.
215
7.03
67.
024
7.01
87.
015
7.00
57.
003
6.84
63.
934
3.92
0
3.25
43.
241
3.23
23.
227
3.21
93.
206
2.12
42.
112
2.10
32.
090
2.08
32.
077
2.07
02.
066
2.06
02.
053
2.04
82.
036
1.84
71.
830
1.81
51.
809
1.79
41.
576
1.55
71.
538
1.28
91.
281
1.27
81.
265
1.25
60.
898
0.88
10.
864
1.00
3.473.480.981.010.32
1.02
1.02
1.17
1.52
2.56
8.16
3.45
SN
O
O
N
3-heptyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (3)
-
S11
-
S12
ppm (t1)102030405060708090100110120130140150160170180190
177.
340
174.
386
156.
010
148.
967
136.
695
132.
515
129.
086
128.
467
126.
409
122.
148
120.
260
77.3
1877
.000
76.6
82
47.1
5446
.931
31.8
3330
.747
29.4
5829
.420
29.3
5229
.236
26.4
8822
.653
14.0
98
SN
O
O
N
5
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.29
68.
285
7.55
47.
550
7.53
47.
531
7.51
57.
511
7.50
17.
483
7.46
37.
412
7.39
97.
394
7.38
97.
375
7.36
67.
363
7.34
57.
260
7.23
57.
215
7.03
57.
023
7.01
97.
006
6.85
3
3.92
53.
911
3.24
33.
234
3.23
13.
222
2.10
32.
091
2.08
32.
077
2.07
12.
067
2.05
42.
049
1.84
81.
831
1.81
61.
795
1.77
51.
573
1.55
51.
537
1.26
40.
897
0.88
00.
863
1.00
3.003.041.081.050.02
3.30
12.70
2.18
1.46
1.07
1.00
1.00
SN
O
O
N
5
3-nonyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (4)
-
S13
ppm (t1)102030405060708090100110120130140150160170180190
177.
291
174.
340
155.
963
148.
897
136.
642
132.
485
129.
029
128.
408
126.
365
122.
080
120.
203
77.3
1877
.000
76.6
82
47.1
0446
.856
31.8
4230
.684
29.5
3629
.458
29.3
7829
.309
29.2
7626
.444
22.6
2414
.072
NS
O
O7
N
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.29
48.
292
8.29
08.
287
8.28
28.
279
8.27
78.
275
7.54
17.
537
7.52
27.
521
7.51
87.
502
7.49
87.
492
7.47
87.
475
7.46
37.
459
7.45
37.
411
7.40
77.
404
7.38
97.
368
7.36
47.
346
7.34
4
7.26
07.
227
7.22
57.
223
7.20
77.
205
7.20
27.
025
7.02
37.
013
7.01
07.
007
7.00
46.
994
6.99
23.
923
3.90
9
3.25
43.
241
3.23
23.
228
3.21
93.
206
2.12
12.
100
2.08
72.
080
2.07
42.
068
2.06
32.
058
2.05
12.
046
2.03
31.
866
1.84
81.
844
1.82
71.
812
1.80
61.
791
1.77
11.
589
1.57
21.
553
1.53
51.
514
1.26
20.
900
0.88
30.
866
1.00
3.353.171.041.09
1.14
1.11
1.17
1.42
2.41
16.25
3.56
NS
O
O7
N
1-phenyl-3-(pyridin-2-ylthio)-4-undecylpyrrolidine-2,5-dione (5)
-
S14
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.29
48.
281
7.54
67.
527
7.50
07.
482
7.46
67.
462
7.41
17.
408
7.39
27.
374
7.36
87.
365
7.35
97.
347
7.26
07.
231
7.21
07.
031
7.01
77.
014
7.00
03.
919
3.90
63.
256
3.24
33.
234
3.22
93.
221
3.20
8
2.12
42.
111
2.10
32.
090
2.08
22.
077
2.07
02.
066
2.06
02.
053
2.04
82.
036
1.86
71.
850
1.84
61.
829
1.81
31.
807
1.79
31.
773
1.58
91.
572
1.55
41.
535
1.51
41.
259
0.89
80.
881
0.86
4
3.20
22.032.17
1.29
1.11
1.00
1.00
1.00
3.093.000.971.01
NS
O
O10
N
1-phenyl-3-(pyridin-2-ylthio)-4-tetradecylpyrrolidine-2,5-dione (6)
-
S15
ppm (t1)102030405060708090100110120130140150160170180190
177.
319
174.
361
155.
994
148.
933
136.
661
132.
504
129.
063
128.
440
126.
384
122.
105
120.
228
77.3
1877
.000
76.6
82
47.1
3146
.884
31.8
8830
.722
29.6
5129
.618
29.5
7129
.495
29.4
1229
.328
26.4
7322
.660
14.1
03
NS
O
O10
N
-
S16
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.22
98.
227
8.21
87.
489
7.48
57.
469
7.46
67.
451
7.44
67.
430
7.42
67.
412
7.39
77.
393
7.34
57.
342
7.33
97.
329
7.32
37.
318
7.30
57.
302
7.29
67.
292
7.28
77.
274
7.19
07.
170
7.15
0
6.97
36.
970
6.96
06.
958
6.95
46.
942
3.87
13.
857
3.18
23.
169
3.16
13.
156
3.14
73.
134
2.03
42.
021
2.01
32.
008
2.00
11.
997
1.99
11.
984
1.97
91.
967
1.80
01.
778
1.76
11.
746
1.74
01.
725
1.70
51.
520
1.50
31.
485
1.46
61.
445
1.18
50.
826
0.80
90.
792
1.00
1.08
6.251.12
1.05
1.02
4.06
2.27
1.48
1.00
28.91
NS
O
O11
N
ppm (t1)102030405060708090100110120130140150160170180190
177.
371
174.
428
156.
035
148.
950
136.
806
132.
558
129.
141
128.
522
126.
451
122.
251
120.
337
77.3
7177
.257
77.0
5476
.736
47.1
9546
.964
31.9
6030
.793
29.7
2829
.692
29.6
4529
.568
29.4
8529
.414
29.4
0026
.545
22.7
3114
.170
NS
O
O11
N
3-pentadecyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (7)
-
S17
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.30
78.
305
8.30
38.
300
8.29
58.
292
8.29
08.
288
7.56
47.
560
7.54
47.
541
7.52
67.
521
7.50
17.
483
7.46
37.
458
7.41
67.
413
7.40
97.
399
7.39
47.
389
7.37
97.
376
7.36
67.
362
7.35
77.
344
7.34
2
7.26
07.
248
7.24
67.
243
7.22
87.
225
7.22
37.
048
7.04
57.
035
7.03
37.
029
7.02
77.
017
7.01
4
3.95
53.
941
3.25
13.
238
3.22
93.
224
3.21
63.
203
2.12
62.
113
2.10
52.
092
2.08
52.
079
2.07
22.
068
2.06
22.
055
2.05
02.
038
1.87
21.
854
1.85
01.
833
1.81
81.
812
1.79
71.
777
1.59
21.
575
1.55
61.
538
1.51
71.
256
0.89
60.
879
0.86
2
1.00
1.031.053.08
3.24
1.03
1.07
1.20
1.35
2.3828.19
3.20
NS
O
O13
N
ppm (t1)102030405060708090100110120130140150160170180190
177.
304
174.
369
155.
974
148.
870
136.
800
132.
508
129.
093
128.
476
126.
404
122.
249
120.
312
77.3
1777
.000
76.6
83
47.1
4946
.926
31.9
1430
.746
29.6
9129
.647
29.6
0029
.524
29.4
3829
.369
29.3
5326
.500
22.6
8314
.119
NS
O
O13
N
3-heptadecyl-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (8)
-
S18
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.29
68.
294
8.29
28.
289
8.28
48.
281
8.27
98.
277
7.54
67.
541
7.52
67.
521
7.50
77.
502
7.48
27.
466
7.46
27.
457
7.41
47.
411
7.40
87.
392
7.36
97.
365
7.36
07.
348
7.34
57.
260
7.23
07.
228
7.22
67.
210
7.20
77.
205
7.02
97.
027
7.01
77.
014
7.01
17.
008
6.99
86.
996
6.84
35.
366
5.35
75.
352
5.34
95.
343
5.33
4
3.91
13.
897
3.25
83.
245
3.23
63.
232
3.22
33.
210
2.05
32.
049
2.03
62.
023
2.00
91.
866
1.84
91.
845
1.82
81.
813
1.80
61.
792
1.77
21.
593
1.57
71.
558
1.54
01.
519
1.31
21.
308
1.26
90.
896
0.88
00.
862
1.00
3.173.111.011.050.04
2.03
1.02
1.02
4.451.43
2.45
22.25
3.32
NS
O
O5
N
5
ppm (t1)102030405060708090100110120130140150160170180190
177.
294
174.
332
156.
003
148.
955
136.
627
132.
508
129.
960
129.
689
129.
054
128.
431
126.
377
122.
075
120.
211
77.3
1877
.000
76.6
82
47.1
2946
.888
31.8
6030
.723
29.7
2629
.656
29.4
8229
.385
29.2
7929
.245
29.1
3427
.186
27.1
3226
.470
22.6
4514
.090
NS
O
O5
N
5
(Z)-3-(heptadec-8-en-1-yl)-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (9)
-
S19
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.27
88.
276
8.27
48.
272
8.26
68.
264
8.26
28.
259
7.51
57.
511
7.49
57.
490
7.48
37.
469
7.45
07.
444
7.40
07.
397
7.39
47.
378
7.36
97.
365
7.36
07.
348
7.34
57.
339
7.26
07.
203
7.18
27.
000
6.99
86.
988
6.98
66.
982
6.98
06.
969
6.96
75.
425
5.39
45.
377
5.36
75.
362
5.35
25.
347
5.30
03.
898
3.88
43.
252
3.23
93.
230
3.22
53.
216
3.20
3
2.79
72.
781
2.76
62.
081
2.06
42.
047
2.03
01.
856
1.83
91.
834
1.81
81.
813
1.80
21.
796
1.78
11.
762
1.58
61.
572
1.55
31.
535
1.51
51.
370
1.34
01.
326
1.32
31.
313
1.30
81.
302
1.28
71.
285
0.90
50.
888
0.87
0
1.00
3.092.970.961.00
4.42
1.07
1.02
2.21
5.30
1.61
2.1214.01
3.20
NS
O
O5
N
4
ppm (t1)102030405060708090100110120130140150160170180190
177.
172
174.
206
155.
917
148.
857
136.
492
132.
446
130.
046
129.
865
128.
924
128.
293
127.
900
127.
751
126.
289
121.
913
120.
077
77.3
1877
.000
76.6
82
47.0
0946
.776
31.3
7130
.595
29.4
5629
.273
29.1
9929
.139
29.0
2927
.062
26.3
7625
.507
22.4
35
13.9
65
NS
O
O5
N
4
3-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-1-phenyl-4-(pyridin-2-ylthio)pyrrolidine-2,5-dione (10)
-
S20
ppm (t1)1.02.03.04.05.06.07.08.09.0
7.40
47.
385
7.37
97.
365
7.29
27.
286
7.28
37.
278
7.27
57.
269
7.26
57.
262
7.25
7
7.18
9
6.36
26.
357
6.35
2
2.46
52.
460
2.44
62.
442
2.42
62.
422
1.61
01.
591
1.57
2
1.33
11.
322
1.31
31.
304
1.29
8
0.87
40.
865
0.85
70.
851
0.84
40.
839
3.30
4.35
2.18
2.19
1.00
2.123.07
N
O
O
ppm (t1)102030405060708090100110120130140150160170180190
170.
424
169.
734
150.
351
131.
610
129.
024
127.
627
126.
306
125.
897
77.3
1877
.203
77.0
0076
.683
31.3
3726
.758
25.4
6022
.300
13.9
01
N
O
O
3-pentyl-1-phenyl-1H-pyrrole-2,5-dione (11)
-
S21
ppm (t1)1.02.03.04.05.06.07.08.09.0
8.3118.3098.2998.2968.2078.1968.1947.5207.5157.5007.4787.4657.4617.4547.4527.4487.4347.4187.4147.4017.3987.3847.3797.3677.3637.3537.3487.3427.3337.3297.3187.2857.2817.2767.2607.2187.1977.1887.1687.0107.0076.9946.9916.9796.9766.9633.6743.6573.640
2.9812.9672.9642.9492.1592.1492.1252.1142.0952.0842.0592.0482.0432.0382.0332.0162.0132.0092.0051.9961.9871.9821.9741.9691.9631.9591.9491.8971.8871.8671.8631.8571.8521.8341.8231.7661.7531.7471.7401.7351.7271.7211.7091.7031.6941.6861.6811.6741.6631.6571.6491.6411.6321.6201.6061.6021.5891.5761.5581.5381.5331.4261.3791.3701.3611.3521.3431.3391.3301.3201.3101.3011.2921.2831.2740.9260.9090.9050.8950.8870.8780.8690.8600.852
5.15
1.07
1.01
1.00
0.44
0.55
0.44
0.61
6.45
8.89
3.99
3.23
CC N
O
O
CC N
O
O
S SN N
3,4-dipentyl-1-phenyl-3-(pyridin-2-ylthio)pyrrolidine-2,5-dione (12a and 12b)
-
S22
ppm (t1)102030405060708090100110120130140150
148.
719
148.
478
136.
245
136.
214
128.
803
128.
652
128.
093
127.
925
126.
182
126.
066
121.
906
120.
023
119.
813
47.9
4947
.667
38.1
3833
.667
31.5
7931
.512
31.4
8028
.577
27.9
0627
.687
24.1
0023
.693
22.1
3822
.092
22.0
7022
.017
13.7
6213
.688
13.6
63
ppm (t1)102030405060708090100110120130140150160170180190
177.524177.104176.857176.171
157.431156.936148.922148.686
136.440136.404132.637132.519
129.002128.850128.291128.122
126.383126.267122.104121.908
120.216120.01177.31877.20377.00076.682
58.99356.903
48.15647.87638.34733.87331.78231.71531.68428.77928.10927.89324.30423.895
22.34122.29422.27222.21913.96313.88913.864
CC N
O
O
CC N
O
O
S SN N
ppm (f2)1.02.03.04.05.06.07.08.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
ppm (f1)
COSY
-
S23
2.903.003.103.203.303.403.503.603.70
8.150
8.200
8.250
8.300
8.350
ppm (t1)
ppm (f2)1.02.03.04.05.06.07.08.0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150ppm (f1)
NOESY
HSQC
-
S24
ppm (t2)1.02.03.04.05.06.07.08.0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190ppm (t1)
HMBC
-
S25
ppm (t1)1.02.03.04.05.06.07.08.09.0
7.33
67.
332
7.31
67.
303
7.29
87.
264
7.26
07.
254
7.24
27.
214
7.21
17.
207
7.19
27.
178
7.17
47.
138
2.35
92.
340
2.32
01.
495
1.49
01.
476
1.46
21.
456
1.26
91.
259
1.25
01.
241
1.23
21.
223
0.81
50.
811
0.80
60.
797
0.79
10.
779
6.00
8.084.04
3.99
4.95
N
O
O
ppm (t1)102030405060708090100110120130140150160170180190
170.
683
141.
073
131.
933
128.
815
127.
157
125.
595
77.3
1877
.000
76.6
82
31.7
36
28.2
5123
.780
22.2
8313
.842
N
O
O
3,4-dipentyl-1-phenyl-1H-pyrrole-2,5-dione (13)