Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 14 Substrate Selective Amide Coupling driven by Encapsulation of a Coupling Agent within a Self-Assembled Hexameric Capsule Sonia Giust, a Giorgio La Sorella, a Laura Sperni, a Giorgio Strukul, a Alessandro Scarso a Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca Foscari di Venezia, Calle Larga S. Marta 2137, 123, Venezia (ITALY) Reagents and Materials. General 1 H NMR were recorded at 298 K, unless otherwise stated, on a Bruker AVANCE spectrometer operating at.1 MHz. δ values in ppm are relative to SiMe4. GC analysis were performed on HP SERIES II 89 equipped with a HP column ( m, I. D.. m, film. μm) using He as gas carrier and FID. GC-MS analyses were performed on a GC Trace GC equipped with a HP-MS column ( m, I.D.. mm, film. m) using He gas carrier and coupled with a quadrupole MS Thermo Finnigan Trace MS with Full Scan method. Solvents and reactants were used as received; otherwise they were purified as reported in the literature. 1 TLC analysis were performed on TLC Polygram Sil G/UV4 of. mm thickness and flash-chromatography separations were performed on silica gel Merk 6, 2- mesh. 2 Substrates and capsule All carboxylic acids 3 and amines 4 as well as the coupling agent 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride 2 are all commercially available products (Aldrich) and were used as received without any further purification. Resorcin[4]arene 1 was prepared as reported in the literature. 3 Amide products were determined by GC-MS analysis. Catalytic Studies Catalytic reactions of amide coupling between acids 3 with amines 4 mediated by the carbodiimide 2 in the presence of the capsule 1 6 8H 2 Water saturated solvent was prepared by shaking chloroform-d with bidistilled water at room temperature in a separation funnel. Resorcin[4]arene 1 (6.6 equivalents, 81.4 mm) was placed in a screw-capped vial equipped with silicone septum and dissolved in the water saturated chloroform-d (1 ml) stirring for few minutes. To this solution, 1-ethyl-3-(-3- dimethylaminopropyl) carbodiimide hydrochloride 2 (1 equivalent, 13.2 mm) was added, followed after few minutes stirring, by octane, decane, dodecane, tetradecane, or docosane as GC-MS standard (3.3 mm), a series of carboxylic acids (. equivalents each, 6.7 mm) and a series of amines (. equivalents each, 6.7 mm). The reaction was then left at 6 C under vigorous stirring for 2 days and the reaction progress was monitored by GC-MS analysis by periodically sampling directly from the reaction mixtures. Conversion, product assignment and distribution were determined by direct GC-MS analysis of the reaction mixture as the average of three experiments. GC-MS analyses were performed on a GC Trace GC coupled with a quadrupole MS Thermo Finnigan Trace MS with Full Scan method. Experimental conditions are reported in the following table.
Experimental conditions for GC-MS analysis Capillary column: HP-MS m,. mm x. m Initial T, C: 8 C for min Rate, C/min: C/min Final T, C: 28 C for min Injector T (split), C: 28 C Gas carrier flow, ml/min..8 ml/min Injected volume, L.8-1 L Solvent delay, min. 4 min. Mass range, amu: - amu Detector voltage, V: V Interface T, C 28 C Source T, C: C Figure S1. 1 H NMR spectra in water saturated chloroform-d: A) 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride 2 (26. mm), B) 2 (26. mm) and 1 6 8H 2 (26. mm) after mixing; C) 2 (26. mm) and 1 6 8H 2 (26. mm) after 1 min; D) 2 (26. mm) and 1 6 8H 2 (26. mm) after min; E) 2 (26. mm) and 1 6 8H 2 (26. mm) after 2 h; F) 2 (26. mm) and 1 6 8H 2 (26. mm) after 3 days; G) 2 (26. mm) and 1 6 8H 2 (26. mm) after 11 days.
Figure S2. 1 H NMR spectra in water saturated chloroform-d: A) 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride 2 (26. mm), B) 2 (26. mm) and 1 6 8H 2 (26. mm) C) 2 (26. mm) and 1 6 8H 2 (26. mm) and tetraethylammonium tetrafluoroborate 6 (26.3 mm); D) 2 (26. mm) and 1 6 8H 2 (26. mm) and tetraethylammonium tetrafluoroborate 6 (26.3 mm) after 3 days; E) Hexameric capsule 1 6 8H 2 (13. mm). Figure S3. 1 H NMR spectra in water saturated chloroform-d: A) Hexameric capsule 1 6 8H 2 (13. mm); B) 1 6 8H 2 (13. mm) with.2 eq. of hexanoic acid; C) 1 6 8H 2 (13. mm) with.4 eq. of hexanoic acid; D) 1 6 8H 2 (13. mm) with.6 eq. of hexanoic acid; E) 1 6 8H 2 (13. mm) with.8 eq. of hexanoic acid; F) 1 6 8H 2 (13. mm) with 1. eq. of hexanoic acid; G)
1 6 8H 2 (13. mm) with 1.2 eq. of hexanoic acid; H) 1 6 8H 2 (13. mm) with 1.6 eq. of hexanoic acid; I) 1 6 8H 2 (13. mm) with 2. eq. of hexanoic acid. Figure S4. 1 H NMR spectra in water saturated chloroform-d: A) Hexameric capsule 1 6 8H 2 (13. mm); B) Hexameric capsule 1 6 8H 2 (13. mm) and.2 eq. of butylamine; C) Hexameric capsule 1 6 8H 2 (13. mm) and.4 eq. of butylamine; D) Hexameric capsule 1 6 8H 2 (13. mm) and.6 eq. of butylamine; E) Hexameric capsule 1 6 8H 2 (13. mm) and.8 eq. of butylamine; F) Hexameric capsule 1 6 8H 2 (13. mm) and 1. eq. of butylamine; G) Hexameric capsule 1 6 8H 2 (13. mm) and 1.2 eq. of butylamine; H) Hexameric capsule 1 6 8H 2 (13. mm) and 1.6 eq. of butylamine; I) Hexameric capsule 1 6 8H 2 (13. mm) and 2. eq. of butylamine. encapsulated n-butylammonium cation.
Figure S6. 1 H NMR spectra in water saturated chloroform-d: A) Hexameric capsule 1 6 8H 2 (13. mm) and.1 eq. of butylamine and.1 eq. of hexanoic acid; B) Hexameric capsule 1 6 8H 2 (13. mm) and.2 eq. of butylamine and.2 eq. of hexanoic acid; C) Hexameric capsule 1 6 8H 2 (13. mm) and.4 eq. of butylamine and.4 eq. of hexanoic acid; D) Hexameric capsule 1 6 8H 2 (13. mm) and.6 eq. of butylamine and.6 eq. of hexanoic acid; E) Hexameric capsule 1 6 8H 2 (13. mm) and.8 eq. of butylamine and.8 eq. of hexanoic acid; F) Hexameric capsule 1 6 8H 2 (13. mm) and 1. eq. of butylamine and 1. eq. of hexanoic acid; G) Hexameric capsule 1 6 8H 2 (13. mm) and 1. eq. of butylamine and 1. eq. of hexanoic acid; H) Hexameric capsule 1 6 8H 2 (13. mm) and 2. eq. of butylamine and 2. eq. of hexanoic acid. encapsulated new species. Figure S7. 1 H NMR spectra in water saturated chloroform-d for the reaction at C monitored every 1h (from bottom to top) for the hexameric capsule 1 6 8H 2 (13. mm) octylamine (6.7 mm) hexanoic acid (6.7 mm) and 2 (13.2 mm).
GC-MS spectra of amide products Reagents RT Product PM C3CH + C42 CCH + C42 C3CH + C82 CCH + C82 CCH + C12 C11CH + C42 C11CH + C82 C12CH + C82 CCH + C162 C11CH + C162 9.7 1.63 11.1 12.27 12.97 12.99 14.31 14.72 1.21.66 Internal Standard 143 ctane 171 Decane 199 Dodecane 227 Tetradecane Tetradecane ctane 311 Docosane 3 Docosane 339 Docosane 423 Tetradecane Sonia-exp7B_714 #9 RT: 9.7 AV: 1 NL: 2.4E T: {;} + c EI det=. Full ms [.-.] 71.21 9 9 8 8 7 7 6 6 4 1 1 43.29 44.28 41.28 73.21 39.27 7. 8.24 88.21 86.19. 11..23 6.23 114.19 4.28 4.23 7.22 74.23 68.22 84.14 12.19 116.22 77.1 89.21 98.19 129.24 142.21 144. 11.16 1.19 11.22 16.9 16.34 17.26 6 7 8 9 11 1 1 1 1 16 17 11.22 Figure S1. GC-MS of aa. C3CH + C42 128.22 M + 143 143.24
Sonia-expB_29714 #14 RT: 1.63 AV: 1 NL: 4.E T: {;} + c EI det=. Full ms [.-.] 9 9 8 8 7 7 6 6 4 1 1 41.29 43.29 44.28 7.27 71.26 73.22 86.21 99.21 11.21.23 6.24 116.22 128.21 87.21 142.23 74. 129.23 16.24 4.28 7.24 84.17 98.22 11.21 171.28 67.23 117.24 1. 143.26 17.26 173. 181. 193. 7.16 6 7 8 9 11 1 1 1 1 16 17 18 19 21 Figure S2. GC-MS of ba. CCH + C42 M + 171 Esca-Exp2B-2gg_714 #1166 RT: 11.1 AV: 1 NL: 3.64E T: {;} + c EI det=. Full ms [.-.] 43.3 71.2 9 9 8 8 7 7 6 6 4 1 1 41.3 44.3 7.3.2 73.2.2 11.2 8.2 114.2 88.2 86.2 6 7 8 9 11 1 1 1 1 16 17 18 19 21 128.2 142.2 69.2 199.3 11.2 129.2 184.3 9.2 17.3 4.3 84.2 12.2 17.3 67.2 46.3 74.2 89.2 98.2 116.2 1.2 143.2 18.3 172.2 18.3 198.3.3 11.2 14.2 7.1 21.8 Figure S3. GC-MS of ab. C3CH + C82 16.2 M + 199
Sonia-exp3B_29714 #127 RT: 12.27 AV: 1 NL: 9.E T: {;} + c EI det=. Full ms [.-.] 43.3 9 9 8 8 7 7 6 6 4 1 1 41.3 44.3 7.3.2 8.2 71.2 69.2 73.2 86.2 99.2.2 114.2 87.2 128.2 129.2 6 8 1 1 16 18 2 2 26 16.2 171.3 184.3 11.2 198.3 116.2 142.2 17.3 227.3 17.2 18.3 74.2 1.2 172.3 4.3 67.2 98.2 199.3 81.2 112.2 143.2 212.3 226.3 228.3 46.3 96.2 117.2 1.2 18.3 173.3 186.3 2.2 3.2 267.3 Figure S4. GC-MS of bb. CCH + C82 M + 227 Sonia-exp1B_714 #1366 RT: 12.97 AV: 1 NL: 8.6E T: {;} + c EI det=. Full ms [.-.] 43.29 9 9 8 8 7 7 6 6 4 1 1 73.21 99.21 71.24 114.22 86.22.21 212.34 44.29.26 184.29 4. 87.22 7.27 16.26 128.23 199.32 8.26 69.22 129.23 11.21 142.24 116.22 17.26 226.36 8. 83.23 17.28 18. 213.34.42 98.19 143..33 112. 1.24 171.27 227.37 14. 168.28 186. 214.34 4. 6.43 281.22 6 8 1 1 16 18 2 2 26 28 Figure S. GC-MS of bc. CCH + C12 M +
Sonia-expB_29714 #1367 RT: 12.98 AV: 1 NL: 1.9E6 T: {;} + c EI det=. Full ms [.-.] 9 9 8 8 7 7 6 6 4 1 1 43.28 7.26 73.22. 11. 128.21. 86.21 72.23 116.21 183.29 87.21 142.23 17.26 8.24 212.33 16.26.41 4. 11.21 171.28.32 226. 2.38 1.23 7.42 281. 287.29 6 8 1 1 16 18 2 2 26 28 Figure S6. GC-MS of ca. C11CH + C42 M + Esca-Exp1B-2gg_714 #148 RT: 14. AV: 1 NL: 3.E T: {;} + c EI det=. Full ms [.-.] 9 9 8 8 7 7 6 6 4 1 1 43.29. 7.27 71. 69.24 73.21 86.22 87.22.21 114.22 128.23 1.27 16. 171.29 184. 226.37 8.24 198.31 4.41 268.4 311.4 98. 212.33 282.47 17.26 6 8 1 1 16 18 2 2 26 28 3 3 Figure S7. GC-MS of cb. 2.39 C11CH + C82 M + 311 283.46 31.3 312.6 327.28 343.33
Esca-Exp1B-2gg_714 #164 RT: 14.71 AV: 1 NL: 3.8E T: {;} + c EI det=. Full ms [.-.] 9 9 8 8 7 7 6 6 4 1 1 43.29. 7.28 71. 69.23 73.21 86.22.21 114.22 87.22 128.24 16.26 171.29 184.29 1.28 4.42 142.24 198.32 2. 226.37 8. 282.48 268.44 3.8 98.21 214. 296.1 17.28 297.1 324.7 326.8 6 8 1 1 16 18 2 2 26 28 3 3 Figure S8. GC-MS of db. C12CH + C82 M + 3 Sonia-exp6B_29714 #1671 RT: 1. AV: 1 NL: 3.3E T: {;} + c EI det=. Full ms [.-.] 43. 9 9 8 8 7 7 6 6 4 1 1 73.22 114.22 71. 99.22.26 86.22.21 16.27 129.23 69.23 142. 8.26 17.28 6 8 1 1 16 18 2 2 26 28 3 3 36 268.46 283.49 296.1 184. 198.32 31.4 212. 2.41 Figure S9. GC-MS of bc. CCH + C162 4.41 269.46 339.61 311.4 M + 339 3.61
Sonia-exp6B_29714 #2419 RT:.66 AV: 1 NL: 2.37E T: {;} + c EI det=. Full ms [.-.] 7.26 9 9 8 8 7 7 6 6 4 1 1 71. 73.21 86.22. 114.22 128.23 142.24 6 8 1 1 16 18 2 2 26 28 3 3 36 38 4 2. 268.4 296. 17.28 183. 4. 7.1 226.37 297.1 2.63 338.9 423.8 38.68 324.6 366.6 394.72 422.79 424.79 Figure S1. GC-MS of cc. C11CH + C162 M + 423 1 D.D. Perrin, W.L.F. Armarego, Purification of laboratory chemicals, 3rd edition,, Pergamon Press, 1993. 2 W. C. Still, M. Khan, A. Mitra J. rg. Chem. 1978, 43, 2923. 3 Y. Aoyama, Y. Tanaka, S. Sugahara, J. Am. Chem. Soc., 1989, 111, 397-4.