Organic Letters Synthesis of Oxygen-Free [2]Rotaxanes: Recognition of Diarylguanidinium Ions by Tetraazacyclophanes Yu-Hsuan Chang, Yong-Jay Lee, Chien-Chen Lai, Yi-Hung Liu, Shie-Ming Peng, and Sheng-Hsien Chiu* Supplementary Material Data Page Number Experimental procedures and characterization data for new compounds... S2 S10 1 H and 13 C NMR spectra of the cyclophane 1, 5, 10 and 13... S11 S18 1 H and 13 C NMR spectra of the dibromide 6 and 15... S19 S22 1 H and 13 C NMR spectra of the salt 9-, 16 and 22 TFPB... S23 S28 1 H and 13 C NMR spectra of the compound S1-S5... S29 S38 1 H and 13 C NMR spectra of the [2]rotaxane (18-21) TFPB... S39 S46 1 H and 13 C NMR spectra of the [2]rotaxane 23 TFPB and 24 TFPB... S47 S50 ITC titration isotherms and thermodynamic data for the complexation of 9 TFPB with the cyclophanes in CHCl 3... S51 S56 Dilution isotherm for the cyclophanes and 9 TFPB in CDCl3... S57 S58 Competition experiment of the cyclophane 1 and 5 with 9 TFPB in CDCl 3... S59 Competition experiment of the cyclophane 10 and 13 with 9 TFPB in CDCl 3... S60 1 H NMR spectra for assembly of [2]rotaxanes from 16 TFPB, cyclophane 1, and aldehyde 17... S61 NOESY spectra for the equimolar mixtures of 9 TFPB and the cyclophanes (20 mm)... S62 S65 ESI-MS spectra of the [2]rotaxane 18-21 TFPB and 23-24 TFPB... S66 S71 S1
General All glassware, stirrer bars, syringes, and needles were either oven- or heat gun-dried prior to use. All reagents were obtained from commercial sources unless otherwise indicated. Reactions were conducted under Ar or N 2 atmospheres. Thin layer chromatography (TLC) was performed on Merck 0.25 mm silica gel (Merck Art. 5715). Column chromatography was performed using Kieselgel 60 (Merck, 70 230 mesh) and Chromatorex NH series / DIOL series (Fuji Silysia, MB100-40/75). Melting points were determined by Fargo MP-2D melting point apparatus. For NMR spectroscopy, the deuterated solvent was used as the lock, and the solvent s residual protons were employed as the internal standard. Cyclophane 1: A CHCl 3 solution mixture (149 ml) of 1,3-phenylenedimethanamine (3) (406 mg, 395 μl, 2.98 mmol) and isophthalaldehyde (2) (400 mg, 2.98 mmol) was stirred at 50 C for 48 h and slowly added to a MeOH solution (298 ml) of NaBH 4 (4.51 g, 119 mmol). The organic solvents were evaporated under reduced pressure and the residue was partitioned between H 2 O (150 ml) and CH 2 Cl 2 (2 150 ml). The combined organic phases were dried (MgSO 4 ), concentrated and purified chromatographically (NH-silica gel; CH 2 Cl 2 /hexanes, 1:1) to afford cyclophane 1 as a white solid (432 mg, 61%); M.p. = 156 157 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 3.78 (s, 16H), 7.19 (d, J = 8.0 Hz, 8H), 7.22 7.28 (m, 10H); 13 C NMR (100 MHz, CDCl 3 ): δ = 53.6, 127.1, 127.8, 128.4, 140.3; HR-MS (ESI): calcd for [1 + Na] + C 32 H 36 N 4 Na + : m/z 499.2832; found 499.2827. Dibromide 6: NaH (60%; 1.45 g, 36.3 mmol) was added to a THF solution (72.4 ml) of 1,3-benzenedimethanol (8) (1 g, 7.24 mmol) and the solution mixture was stirred at room temperature for 30 min. The solution mixture was then added 1,3-bis(bromomethyl)benzene (7.64 g, 28.9 mmol) and heated to reflux for 16 h. After cooled to room temperature, the solution mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified chromatographically (SiO 2 ; EtOAc/hexanes, 1:9) to afford dibromide 6 as a light brown oil (1.47 g, 40%).; 1 H NMR (400 MHz, CDCl 3 ): δ = 4.48 (s, 4H), 4.54 (s, 4H), 4.56 (s, 4H), 7.26 7.32 (m, 8H), 7.32 7.40 (m, 4H); 13 C NMR (100 MHz, CDCl 3 ): δ = 33.4, 71.8, 72.3, 127.2, 127.8, 128.3, 128.3, 128.6, 128.9, 138.0, 138.3, 139.0 (one signal is missing, possibly because of signal overlap); HR-MS (ESI): calcd for [6 + Na] + C 24 H 24 Br 2 O 2 Na + : m/z 525.0035; found 525.0034. Cyclophane 5: A THF solution mixture (32.4 ml) of the dibromide 6 (816 mg, 1.62 mmol) and 1,3-benzenedimethanol (8) (224 mg, 1.62 mmol) was added to a S2
suspension of THF solution suspension (129.4 ml) of NaH (60%; 324 mg, 8.10 mmol) and the solution mixture was heated to reflux for 7 days. After cooled to room temperature, the solution mixture was filtered through Celite and the filtrate was concentrated under reduced pressure. The residue was purified chromatographically (SiO 2 ; EtOAc/hexanes, 1:9) to afford cyclophane 5 as a white solid (362 mg, 47%); M.p. = 144 145 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 4.52 (s, 16H), 7.21 7.34 (m, 16H); 13 C NMR (100 MHz, CDCl 3 ): δ = 72.1, 127.2, 127.4, 128.4, 138.4; HR-MS (ESI): calcd for [5 + Na] + C 32 H 32 NaO + 4 : m/z 503.2193; found 503.2182. Guanidinium Salt 9 TFPB: HCl (aq) (3N, 297 μl) was added to a CH 3 CN solution (17.8 ml) of 1,3-di-p-tolylguanidine [a] (213 mg, 0.890 mmol) and the solution mixture was stirred at room temperature for 10 min before the addition of NaTFPB (789 mg, 0.890 mmol). The solution mixture was stirred at room temperature for 10 min and the organic solvent was removed under reduced pressure. The residue was partitioned between DI water (30 ml) and CH 2 Cl 2 (2 30 ml) and the combined organic layers were dried (MgSO 4 ) and concentrated. The residue was purified chromatographically (SiO 2 gel; CH 2 Cl 2 ) and the product was precipitated from hexanes to afford guanidinium salt 9 TFPB as a pale yellow solid (879 mg, 89%); M.p. = 175 176 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 2.33 (s, 6H), 5.44 (br, 2H), 7.02 (d, J = 7.8 Hz, 4H), 7.16 (br, 2H), 7.23 (d, J = 7.8 Hz, 4H), 7.49 (s, 4H), 7.68 (s, 8H); 13 C NMR (100 MHz, CDCl 3 ): δ =20.9, 117.4 117.8 (m), 124.5 (q, 1 J CF = 271 Hz), 126.3, 127.7, 128.4 129.6 (m), 131.8, 134.8, 141.7, 155.1, 161.7 (q, 1 J CB = 49 Hz); HR-MS (ESI): calcd for [9] + C 15 H 18 N + 3 : m/z 240.1495; found 240.1511. Cyclophane 10: A CH 2 Cl 2 solution mixture (242 ml) of 1,4-phenylenedimethanamine (11) (330 mg, 2.42 mmol) and isophthalaldehyde (2) (325 mg, 2.42 mmol) was stirred at 50 C for 4 d and cooled to 0 o C before the addition of a solution mixture of MeOH/THF/toluene (200 ml/30 ml/30 ml) and NaBH 4 (3.70 g, 97.8 mmol). The solution mixture was stirred at 0 o C for 1 h and the organic solvents were removed under reduced pressure. The residue was partitioned between H 2 O (250 ml) and CH 2 Cl 2 (2 250 ml) and the combined organic layers were dried (MgSO 4 ), concentrated, and purified chromatographically (NH-silica gel; CH 2 Cl 2 /hexanes, 1:1) to afford syslophane 10 as a white solid (301 mg, 52%); M.p. = 133 134 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 3.77 (s, 8H), 3.80 (s, 8H), 7.18 7.22 (m, 4H), 7.26 7.31 (m, 2H), 7.32 (s, 8H), 7.44 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = 52.3, 52.5, 126.9, 127.4, 128.3, 128.4, 139.0, 140.5; HR-MS (ESI): calcd for [10 + Na] + C 32 H 36 N 4 Na + : m/z 499.2832; found 499.2839. S3
Dibromide 15: NaH (60%; 1.45 g, 36.3 mmol) was added to a THF solution (72.4 ml) of 1,3-benzenedimethanol (8) (1 g, 7.24 mmol) and the solution mixture was stirred at room temperature for 30 min. The solution mixture was then added 1,4-bis(bromomethyl)benzene (7.64 g, 28.9 mmol) and heated to reflux for 16 h. After cooled to room temperature, the mixture was filtered through Celite and the filtrate was concentrated. The residue was purified chromatographically (SiO 2 ; EtOAc/hexanes, 1:15) to afford dibromide 15 as a light brown oil (1.75 g, 48%).; 1 H NMR (400 MHz, CDCl 3 ): δ = 4.48 (s, 4H), 4.53 (s, 4H), 4.55 (s, 4H), 7.25 7.29 (m, 2H), 7.29 7.34 (m, 5H), 7.34 7.38 (m, 5H); 13 C NMR (100 MHz, CDCl 3 ): δ = 33.3, 71.7, 72.2, 127.0, 127.1, 128.1, 128.5, 129.1, 137.1, 138.4, 138.6; HR-MS (ESI): calcd for [15 + Na] + C 24 H 24 Br 2 NaO + 2 : m/z 525.0035; found 525.0042. Cyclophane 13: A THF solution (23.8 ml) of the dibromide 15 (600 mg, 1.19 mmol) and 1,3-benzenedimethanol (8) (164 mg, 1.19 mmol) was added to a THF solution suspension (95.2 ml) of NaH (60%; 240 mg, 6.00 mmol) and the solution mixture was heated to reflux for 7 days. After cooled to room temperature, the mixture was filtered through Celite and the filtrate was concentrated. The residue was purified chromatographically (SiO 2 ; EtOAc/hexanes, 1:5) to afford cyclophane 13 as a white solid (68 mg, 12%); M.p. = 184 185 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 4.55 (s, 8H), 4.57 (s, 8H), 7.25 (d, J = 7.5 Hz, 4H), 7.30 7.36 (m, 2H), 7.39 (s, 8H), 7.57 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = 71.4, 71.5, 127.0, 127.0, 127.9, 128.3, 137.7, 138.6; HR-MS (ESI): calcd for [13 + Na] + C 32 H 32 NaO + 4 : m/z 503.2193; found 503.2185. S4
Thiourea S1: 1,3-di-tert-butyl-5-isothiocyanatobenzene (1.58 g, 6.39 mmol) and tert-butyl 4-aminobenzylcarbamate (945 mg, 4.25 mmol) were added to a 10 ml ball-mill jar and the solid mixture was ball-milled at room temperature for 24 h (a 30 min break was taken every 2 h to avoid overheating of the ball-miller). The solid mixture was purified chromatographically (SiO 2 ; CH 2 Cl 2 /hexanes, 2:8) to afford thiourea S1 as a brown oil (1.29 g, 65%); M.p. = 87 88 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.30 (s, 18H), 1.43 (s, 9H), 4.28 (d, J = 4.6 Hz, 2H), 4.84 (br, 1H), 7.16 (s, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.34 (s, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.71 (s, 1H), 7.80 (s, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ = 28.4, 31.3, 35.0, 44.1, 79.6, 119.6, 121.3, 125.1, 128.2, 136.0, 136.7, 137.4, 152.8, 155.9, 179.7 ; HR-MS (ESI): calcd for [S1 + Na] + C 27 H 39 N 3 O 2 SNa + : m/z 492.2655; found 492.2673. Guanidine S2. A DMF solution (2.02 ml) of thiourea S1 (94.8 mg; 0.202 mmol) was cooled to 0 o C and sequentially added NH 4 OH (aq) (35%; 40.4 mg, 45.9 μl, 0.404 mmol), triethylamine (81.8 mg, 113 μl,0.808 mmol) and HgCl 2 (110 mg, 0.405 mmol). The solution mixture was stirred virgrously at 0 o C. After the color turned black, the solution mixture was slowly warmed to room temperature and stirred for 1 h. The solution suspension was then added CH 2 Cl 2 (20 ml) and filtered through Celite. The filtrate was concentrated and the residue was partitioned between H 2 O (20 ml) and CH 2 Cl 2 (2 20 ml). The combined organic layers were dried (MgSO 4 ), concentrated, and purified chromatographically (NH-silica gel; EtOAc/hexanes, 4:6) to afford guanidine S2 as a pale yellow solid (68.1 mg, 75%); M.p. = 85 86 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.24 (s, 18H), 1.44 (s, 9H), 4.22 (s, 2H), 4.92 (br, 1H), 5.03 (br, 2H), 6.93 (d, J = 1.5 Hz, 2H), 7.02 (d, J = 7.6 Hz, 2H),7.09 (s, 1H), 7.15 (d, J = 7.6 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = 28.4, 31.4, 34.8, 44.3, 79.4, 117.7, 117.9, 123.2, 133.0, 141.3, 144.8, 150.2, 152.0, 155.9; HR-MS (ESI): calcd for [S2 + H] + C 27 H 41 N 4 O + 2 : m/z 453.3224; found 453.3234. Guanidine S3. A THF solution (3.92 ml) of guanidine S2 (177 mg, 0.391 mmol) was added HCl (12 N, 980 μl) and stirred for 2 h. The organic solvent was removed under reduced pressure and the residue was partitioned between NaOH (aq) (10%, 40 ml) and CH 2 Cl 2 (2 40 ml). The combined organic layers were dried (MgSO 4 ), concentrated and purified chromatographically (NH-silica gel; MeOH/CH 2 Cl 2, 4:96) to afford guanidine S3 as a pale yellow solid (128 mg, 93%).; M.p. = 90 91 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.22 (s, 18H), 3.72 (s, 2H), 6.92 (s, 2H), 7.02 7.08 (m, 3H), 7.14 (d, J = 8.1 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = 31.3, 34.7, 45.9, 117.6, 117.7, 123.2, 128.0, 137.5, 141.9, 143.7, 150.5, 151.7; HR-MS (ESI): calcd for [S3 + H] + C 22 H 33 N + 4 : m/z 353.2700; found 353.2704. S5
Guanidinium Salt 16 TFPB: A CH 3 CN solution (8.00 ml) of guanidine S3 (141 mg, 0.400 mmol) was added HCl (aq) (3N, 133 μl) and stirred at room temperature for 10 min. The solution mixture was then added NaTFPB (354 mg, 0.399 mmol) and stirred for another 10 min. The organic solvent was removed under reduced pressure and the residue was partitioned between DI water (20 ml) and CH 2 Cl 2 (2 20 ml). The combined organic layers were dried (MgSO 4 ) and concentrated. The residue was purified chromatographically (Diol-silica gel, MeOH/CH 2 Cl 2, 1:99) to afford guanidinium salt 16 TFPB as a pale yellow solid (444 mg, 91%); M.p. = 75 76 C; 1 H NMR (400 MHz, CD 2 Cl 2 ): δ = 1.32 (s, 18H), 3.79 (s, 2H), 7.06 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 1.6 Hz, 2H), 7.27 (d, J = 8.3 Hz, 2H), 7.58 (s, 4H), 7.60 (t, J = 1.6 Hz, 1H), 7.76 (t, J = 2.1 Hz, 8H); 13 C NMR (100 MHz, CD 2 Cl 2 ): δ = 31.4, 35.7, 45.6, 118.0 118.4 (m), 121.4, 125.2, 125.4 (q, 1 J CF = 271 Hz), 127.7, 129.0 130.2 (m), 130.3, 132.0, 132.0, 135.6, 143.0, 155.3, 155.9, 162.5 (q, 1 J CB = 50 Hz); HR-MS (ESI): calcd for [16 TFPB + H] + C 54 H 46 BF 24 N + 4 : m/z 1217.3427; found 1217.3423. [2]Rotaxane 18 TFPB: 1,3-di-tert-butylbenzaldehyde (9.11 mg, 41.7 μmol) was added to a CHCl 3 solution mixture (2.09 ml) of guanidinium salt 16 TFPB (50.7 mg, 41.7 μmol) and cyclophane 1 (19.9 mg, 41.7 μmol) and the solution mixture was stirred at 50 C for 16 h. The solution mixture was then slowly added to a MeOH solution (4.17 ml) of NaBH 4 (31.6 mg, 835 μmol) and the organic solvents were removed under reduced pressure. The residue was partitioned between DI water (10 ml) and CH 2 Cl 2 (2 10 ml) and the combined organic layers were dried (MgSO 4 ) and concentrated. The residue was purified chromatographically (Diol-silica gel; CH 2 Cl 2 /hexanes, 1:1) to afford [2]rotaxane 18 TFPB as a colorless oil (43.6 mg, 55%).; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.22 (s, 18H), 1.33 (s, 18H), 3.63 3.81 (m, 20H), 6.45 (d, J = 8.0 Hz, 2H), 6.76 (s, 2H), 6.91 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 7.4 Hz, 8H), 7.17 (s, 2H), 7.20 7.26 (m, 4H), 7.32 (s, 4H), 7.36 (s, 1H), 7.41 (s, 1H), 7.49 (s, 4H), 7.71 (s, 8H); 13 C NMR (100 MHz, CDCl 3 ): δ = 31.1, 31.5, 34.8, 35.0, 52.4, 54.2, 54.6, 117.2 117.6 (m), 119.8, 121.4, 123.1, 124.6 (q, 1 J CF = 271 Hz), 125.8, 128.1, 128.2, 128.3 129.4 (m), 129.1, 129.4, 132.1, 133.1, 134.8, 138.7, 139.3, 140.9, 151.1, 153.9, 154.5, 161.7 (q, 1 J CB = 50 Hz); HR-MS (ESI): calcd for [18] + C 69 H 91 N + 8 : m/z 1031.7361; found 1031.7362. [2]Rotaxane 19 TFPB: 1,3-di-tert-butylbenzaldehyde (2.05 mg, 9.39 μmol) was added to a CHCl 3 solution mixture (471 μl) of the threadlike salt 16 TFPB (11.4 mg, 9.37 μmol) and the cyclophane 5 (4.51 mg, 9.38 μmol) and the solution mixture was stirred at 50 C for 16 h. The solution mixture was then slowly added to a MeOH S6
solution (941 μl) of NaBH 4 (7.12 mg, 188 μmol) and the organic solvents were removed under reduced pressure. The residue was partitioned between DI water (10 ml) and CH 2 Cl 2 (2 10 ml) and the combined organic layers were dried (MgSO 4 ) and concentrated. The residue was purified chromatographically (Diol-silica gel; CH 2 Cl 2 /hexanes, 3:7) to afford [2]rotaxane 19 TFPB as a colorless oil (7.7 mg, 43%).; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.23 (s, 18H), 1.33 (s, 18H), 3.81 (s, 4H), 4.43 (d, J = 10.6 Hz, 8H), 4.46 (d, J = 10.6 Hz, 8H), 6.31 (s, 2H), 6.46 (d, J = 7.8 Hz, 2H), 6.68 (s, 1H), 7.02 7.13 (m, 12H), 7.13 7.21 (m, 9H), 7.34 (s, 1H), 7.36 (s, 1H), 7.49 (s, 4H), 7.70 (s, 8H); 13 C NMR (100 MHz, CDCl 3 ): δ = 31.2, 31.5, 34.8, 35.0, 52.5, 54.1, 73.9, 117.2 117.6 (m), 119.6, 121.3, 122.1, 123.0, 124.6 (q, 1 J CF = 271 Hz), 125.8, 128.5, 128.8, 128.9, 128.3 129.6 (m), 129.4, 130.5, 131.3, 134.8, 137.3, 138.9, 141.6, 151.0, 152.4, 153.2, 161.7 (q, 1 J CB = 50 Hz); HR-MS (ESI): calcd for [19] + C 69 H 87 N 4 O + 4 : m/z 1035.6722; found 1035.6745. [2]Rotaxane 20 TFPB: 1,3-di-tert-butylbenzaldehyde (79.1 mg, 0.362 mmol) was added to a CH 2 Cl 2 solution mixture (18.1 ml) of the guanidinium salt 16 TFPB (441 mg, 0.362 mmol) and cyclophane 10 (173 mg, 0.363 mmol) and the solution mixture was stirred at 50 C for 6 h. The solution mixture was then slowly added to a MeOH solution (36.2 ml) of NaBH 4 (274 mg, 7.24 mmol) and the organic solvents were evaporated under reduced pressure. The residue was partitioned between DI water (20 ml) and CH 2 Cl 2 (2 20 ml) and the combined organic layers were dried (MgSO 4 ) and concentrated. The residue was purified chromatographically (Diol-silica gel; CH 2 Cl 2 /hexanes, 7:3) to afford [2]rotaxane 20 TFPB as a colorless oil (60 mg, 9%).; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.34 (s, 36H), 3.61 (s, 2H), 3.65 (s, 8H), 3.68 3.74 (m, 6H), 3.77(d, J = 12.7 Hz, 4H), 6.14 (d, J = 8.1 Hz, 2H), 6.69 6.78 (br, 2H), 6.80 (s, 2H), 7.05 (m, 10H), 7.14 (d, J = 7.7 Hz, 4H), 7.17 (s, 2H), 7.20 7.25 (m, 2H), 7.37 (s, 1H), 7.47 (s, 1H), 7.49 (s, 4H), 7.69 (s, 8H); 13 C NMR (100 MHz, CDCl 3 ): δ = 31.2, 31.5, 34.9, 35.2, 52.3, 53.4, 53.7, 54.1, 117.2 117.6 (m), 119.4, 121.7, 122.2, 122.3, 123.1, 124.5 (q, 1 J CF = 271 Hz), 124.6, 127.7, 128.1, 128.8, 128.3 129.4 (m), 129.0, 129.1, 132.0, 133.0, 134.8, 138.4, 139.3, 151.2, 153.4, 154.2, 161.7 (q, 1 J CB = 50 Hz) (one signal was missing, possibly because of signal overlap); HR-MS (ESI): calcd for [20] + C 69 H 91 N + 8 : m/z 1031.7361; found 1031.7404. [2]Rotaxane 21 TFPB: 1,3-di-tert-butylbenzaldehyde (17.1 mg, 78.3 μmol) was added to a CHCl 3 solution mixture (3.92 ml) of the guanidinium salt 16 TFPB (95.4 mg, 78.4 μmol) and cyclophane 13 (37.7 mg, 78.4 μmol) and the solution mixture was stirred at 50 C for 16 h. The solution mixture was then slowly added to a MeOH solution (7.85 ml) of NaBH 4 (59.4 mg, 1.57 mmol) and the organic solvents were S7
removed under reduced pressure. The residue was partitioned between DI water (10 ml) and CH 2 Cl 2 (2 10 ml) and the combined organic layers were dried (MgSO 4 ) and concentrated. The residue was purified chromatographically (Diol-silica gel; CH 2 Cl 2 /hexanes, 6:4) to afford [2]rotaxane 21 TFPB as a colorless oil (20.1 mg, 13%).; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.27 (s, 18H), 1.32 (s, 18H), 3.84 (s, 2H), 3.86 (s, 2H), 4.00 (br, 2H), 4.39 (d, J = 10.1 Hz, 4H), 4.44 (d, J = 10.1 Hz, 4H), 4.48 (d, J = 10.6 Hz, 4H), 4.53 (d, J = 10.6 Hz, 4H), 6.38 (s, 2H), 6.44 (br, 2H), 6.49 (d, J = 7.9 Hz, 2H), 6.89 (s, 8H), 7.16 7.32 (m, 11H), 7.36 (s, 1H), 7.39 (s, 1H), 7.48 (s, 4H), 7.69 (s, 8H); 13 C NMR (100 MHz, CDCl 3 ): δ = 31.2, 31.5, 34.8, 35.1, 52.6, 54.2, 54.1, 73.5, 117.2 117.6 (m), 119.6, 121.3, 122.2, 123.3, 124.6 (q, 1 J CF = 271 Hz), 124.8, 127.5, 128.4, 128.3 129.4 (m), 129.0, 129.2, 129.7, 130.5, 131.3, 134.8, 137.3, 137.9, 138.9, 141.6, 151.1, 152.1, 153.8, 161.7 (q, 1 J CB = 50 Hz); HR-MS (ESI): calcd for [21] + C 69 H 87 N 4 O + 4 : m/z 1035.6722; found 1035.6771. Thiourea S4: 1,3-di-tert-butyl-5-isothiocyanatobenzene (50.2 mg, 0.203 mmol) was added to a THF solution (2.01 ml) of 3,5-di-tert-butylbenzylaniline (41.3 mg, 0.201 mmol) and the solution mixture was heated at 50 o C for 16 h. The organic solvent was removed under reduced pressure and the residue was purified chromatographically (SiO 2 ; CH 2 Cl 2 /hexanes, 4:6) to afford thiourea S4 as a pale yellow solid (55.0 mg, 60%).; M.p. = 89 90 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.30 (s, 36H), 7.22 (s, 4H), 7.29 (s, 2H), 7.91 (br, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = 31.3, 35.0, 119.0, 120.7, 136.5, 152.3, 179.1; HR-MS (ESI): calcd for [S4 + H] + C 29 H 45 N 2 S + : m/z 453.3298; found 453.3318. Guanidine S5: A DMF solution (6.41 ml) of thiourea S4 (301 mg; 0.665 mmol) was cooled to 0 o C and sequentially added (35%; 133 mg, 151 μl, 1.33 mmol), triethylamine (269 mg, 371 μl,2.66 mmol), and HgCl 2 (361 mg, 1.33 mmol). The solution mixture was stirred virgrously at 0 o C. After the color turned black, the S8
solution mixture was slowly warmed to room temperature and stirred for 1 h. The solution suspension was then added CH 2 Cl 2 (40 ml) and filtered through Celite. The filtrate was concentrated and the residue was partitioned between H 2 O (40 ml) and CH 2 Cl 2 (2 40 ml). The combined organic layers were dried (MgSO 4 ), concentrated, and purified chromatographically (NH-silica gel; EtOAc/hexanes, 2:8) to afford guanidine S5 as a white solid (222 mg, 77%).; M.p. = 205 206 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.27 (s, 36H), 6.94 (d, J = 1.5 Hz, 4H), 7.10 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = 31.4, 34.8, 117.4, 118.0, 143.1, 150.4, 151.8; HR-MS (ESI): calcd for [S5 + H] + C 29 H 46 N + 3 : m/z 436.3686; found 436.3708. Guanidinium Salt 22 TFPB: A CH 3 CN solution (8.00 ml) of guanidine S5 (118 mg, 0.271 mmol) was added HCl (aq) (3N, 90.3 μl) and stirred at room temperature for 10 min. The solution mixture was then added NaTFPB (240 mg, 0.271 mmol) and stirred for another 10 min. The organic solvent was removed under reduced pressure and the residue was partitioned between DI water (20 ml) and CH 2 Cl 2 (2 20 ml). The combined organic layers were dried (MgSO 4 ) and concentrated. The residue was purified chromatographically (SiO 2, CH 2 Cl 2 /hexanes, 1:1) and the product was precipitated in hexanes to afford guanidinium salt 22 TFPB as a pale yellow solid (302 mg, 86%); M.p. = 71 72 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.31 (s, 36H), 5.56 (br, 2H), 7.13 (s, 4H), 7.29 (br, 2H), 7.56 (s, 4H) 7.61 (s, 2H), 7.76 (s, 8H); 13 C NMR (100 MHz, CDCl 3 ): δ = 31.0, 35.1, 117.4 117.8 (m), 120.5, 124.6 (q, 1 J CF = 271 Hz), 124.9, 128.4 129.6 (m), 130.5, 134.8, 155.0, 155.2, 161.8 (q, 1 J CB = 50 Hz); HR-MS (ESI): calcd for [22] + C 29 H 46 N + 3 : m/z 436.3686; found 436.3708. [2]Rotaxane 23 TFPB: A CHCl 3 solution mixture (442 μl) of the dumbbell-shaped salt 22 TFPB (11.5 mg, 8.85 μmol), 1,3-phenylenedimethanamine (3) (2.41 mg, 2.34 μl, 17.7 μmol) and isophthalaldehyde (2) (2.37 mg, 17.7 μmol) was stirred at 50 C for 10 d and the solution mixture was slowly added to a MeOH solution (1.77 ml) of NaBH 4 (13.4 mg, 354 μmol). The organic solvents were removed under reduced pressure and the residue was partitioned between DI water (10 ml) and CH 2 Cl 2 (2 10 ml). The combined organic layers were dried (MgSO 4 ), concentrated, and purified chromatographically (SiO 2 gel; CH 2 Cl 2 /hexanes, 7:3) to afford [2]rotaxane 23 TFPB as a white solid (12.6 mg, 80%).; M.p. = 185 186 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.15 (s, 36H), 3.72 (s, 16H), 6.69 (s, 4H), 7.14 (d, J = 7.1 Hz, 8H), 7.19 7.24 (m, 4H), 7.36 (s, 2H), 7.38 (s, 4H), 7.50 (s, 4H), 7.72 (s, 8H); 13 C NMR (100 MHz, CDCl 3 ): δ = 31.1, 35.0, 54.5, 117.2 117.6 (m), 119.4, 122.8, 124.6 (q, 1 J CF = 271 Hz), 128.1, 128.1, 128.3 129.4 (m), 129.2, 133.3, 134.8, 139.3, 153.6, 154.1, 161.7 (q, 1 J CB = 50 Hz); HR-MS (ESI): calcd for [23] + C 61 H 82 N + 7 : m/z 912.6626; S9
found 912.6627. [2]Rotaxane 24 TFPB: A CHCl 3 solution mixture (2.80 ml) of the dumbbell-shaped salt 22 TFPB (35.8 mg, 0.275 mmol), 1,4-phenylenedimethanamine (11) (7.50 mg, 0.551 mmol) and isophthalaldehyde (2) (7.39 mg, 0.551 mmol) was stirred at 50 C for 72 h and then slowly added to a MeOH solution (11.0 ml) of NaBH 4 (83.3 mg, 2.20 mmol). The organic solvents were removed under reduced pressure and the residue was partitioned between DI water (20 ml) and CH 2 Cl 2 (2 20 ml). The combined organic layers were dried (MgSO 4 ), concentrated and purified chromatographically (SiO 2 gel; CH 2 Cl 2 /hexanes, 8:2) to afford [2]rotaxane 24 TFPB as a white solid (27.6 mg, 56%).; M.p. = 193 194 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 1.26 (s, 36H), 3.65 (s, 8H), 3.73 (s, 8H), 6.49 (d, J = 1.3 Hz, 4H), 6.97 (s, 8H), 7.14 (s, 2H), 7.22 (d, J = 7.3 Hz, 4H), 7.27 7.33 (m, 3H), 7.41 (s, 2H), 7.50 (s, 4H), 7.70(s, 8H); 13 C NMR (100 MHz, CDCl 3 ): δ = 31.2, 35.1, 53.3, 53.6, 117.2 117.6 (m), 118.2, 122.7, 124.5 (q, 1 J CF = 271 Hz), 127.8, 127.9, 128.3 129.4 (m), 128.9, 129.1, 132.6, 134.8, 139.1, 139.5, 152.9, 153.8, 161.2 (q, 1 J CB = 49 Hz); HR-MS (ESI): calcd for [24] + C 61 H 82 N + 7 : m/z 912.6626; found 912.6641. Reference: [a] Xing, H.; Zhang, Y.; Lai, Y.; Jiang, Y.; Ma, D. J. Org. Chem., 2012, 77, 5449 5453 S10
7.269 7.254 7.249 7.240 7.232 7.197 7.177 3.778 9 8 7 6 5 4 3 2 1 ppm 8.074 10.266 S11 16.000
140.290 128.382 127.804 127.056 77.318 77.000 76.682 53.572 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S12
7.304 7.283 7.266 7.240 4.519 9 8 7 6 5 4 3 2 1 ppm 16.599 16.000 S13
138.368 128.414 127.364 127.200 77.318 77.000 76.682 72.112 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S14
7.438 7.324 7.303 7.287 7.283 7.266 7.240 7.210 7.208 7.191 3.797 3.769 9 8 7 6 5 4 3 2 1 ppm 2.000 7.985 2.393 4.126 8.156 8.034 S15
140.478 139.038 128.374 128.332 127.442 126.903 77.318 77.000 76.682 52.520 52.346 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S16
7.573 7.394 7.352 7.333 7.316 7.259 7.240 4.573 4.547 9 8 7 6 5 4 3 2 1 ppm 2.000 7.964 2.901 4.254 16.304 S17
138.595 137.671 128.304 127.920 127.005 126.963 77.317 77.000 76.683 71.524 71.383 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S18
7.382 7.363 7.347 7.332 7.316 7.305 7.291 7.288 7.280 7.268 7.240 4.563 4.543 4.475 9 8 7 6 5 4 3 2 1 ppm 4.101 7.800 4.123 4.048 4.000 S19
138.978 138.336 137.950 128.892 128.596 128.309 128.278 127.751 127.191 77.318 77.000 76.683 72.251 71.811 33.415 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S20
7.369 7.348 7.330 7.310 7.284 7.266 7.240 4.546 4.535 4.481 9 8 7 6 5 4 3 2 1 ppm 5.058 5.225 2.313 3.882 4.196 3.966 S21
138.645 138.367 137.136 129.117 128.545 128.072 127.078 127.046 77.318 77.000 76.682 72.157 71.713 33.291 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S22
7.688 7.496 7.240 7.220 7.164 7.031 7.011 5.438 2.332 9 8 7 6 5 4 3 2 1 ppm 8.000 3.911 4.645 1.257 4.010 1.658 5.962 S23
131.786 129.446 129.160 129.133 128.848 128.818 128.572 127.738 126.295 125.864 123.155 120.446 117.604 117.568 117.530 162.405 161.910 161.413 160.920 155.071 141.705 134.769 131.786 129.446 129.160 129.133 128.848 128.818 128.572 127.738 126.295 125.864 123.155 120.446 117.604 117.568 117.530 77.317 77.000 76.683 20.911 130 128 126 124 122 120 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S24
7.758 7.753 7.604 7.600 7.596 7.581 7.281 7.261 7.125 7.121 7.066 7.045 5.322 5.320 5.318 3.790 1.321 9 8 7 6 5 4 3 2 1 ppm 8.000 0.973 3.908 1.996 1.915 1.971 2.008 18.096 S25
130.278 130.127 129.840 129.812 129.783 129.758 129.498 129.471 129.416 129.158 127.737 126.707 125.238 124.000 121.442 121.293 118.225 118.187 163.275 162.780 162.284 161.789 155.866 155.304 143.033 135.555 131.970 131.951 130.278 130.127 129.840 129.812 129.783 129.758 129.498 129.471 129.416 129.158 127.737 126.707 125.238 124.000 121.442 121.293 118.225 118.187 54.541 54.270 54.000 53.730 53.459 45.574 35.715 31.440 132 130 128 126 124 122 120 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S26
7.761 7.608 7.560 7.293 7.240 7.125 5.559 1.306 9 8 7 6 5 4 3 2 1 ppm 8.000 2.010 3.992 1.677 3.933 1.893 35.978 S27
130.503 129.505 129.192 129.165 128.879 128.852 128.671 128.565 125.962 124.975 123.254 120.530 117.571 162.518 162.022 161.528 161.032 155.153 154.998 134.836 130.503 129.505 129.192 129.165 128.879 128.852 128.671 128.565 125.962 124.975 123.254 120.530 117.571 77.318 77.000 76.682 35.143 30.951 130 128 126 124 122 120 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S28
7.764 7.679 7.375 7.354 7.344 7.340 7.284 7.263 7.240 7.162 7.159 4.840 4.288 4.274 1.434 1.304 9 8 7 6 5 4 3 2 1 ppm 1.000 1.020 2.002 0.962 2.107 1.998 0.930 2.037 8.999 17.860 S29
179.728 155.855 152.758 137.448 136.722 135.995 128.174 125.101 121.324 119.591 79.623 77.317 77.000 76.683 44.098 35.003 31.299 28.355 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S30
7.240 7.160 7.141 7.093 7.033 7.014 6.927 6.923 5.032 4.923 4.215 1.437 1.243 9 8 7 6 5 4 3 2 1 ppm 1.916 1.099 1.974 1.969 1.379 0.784 2.040 9.000 18.243 S31
155.910 151.957 150.170 144.832 141.325 133.031 128.531 123.217 117.904 117.748 79.366 77.318 77.000 76.682 44.271 34.803 31.350 28.394 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S32
7.240 7.155 7.135 7.066 7.058 7.037 6.916 3.719 1.223 9 8 7 6 5 4 3 2 1 ppm 2.052 2.940 1.909 S33 2.000 18.001
151.738 150.523 143.726 141.862 137.512 127.950 123.183 117.725 117.564 77.318 77.000 76.682 45.910 34.691 31.281 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S34
7.906 7.285 7.240 7.224 1.295 9 8 7 6 5 4 3 2 1 ppm 1.645 2.000 4.004 36.143 S35
179.146 152.299 136.539 120.711 118.986 77.317 77.000 76.683 34.982 31.312 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S36
7.240 7.101 6.943 6.939 1.272 9 8 7 6 5 4 3 2 1 ppm 2.040 4.000 36.556 S37
151.783 150.427 143.084 118.013 117.399 151.783 150.427 143.084 118.013 117.399 77.318 77.000 76.683 34.803 31.411 155 150 145 140 135 130 125 120 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S38
7.708 7.495 7.411 7.361 7.322 7.251 7.240 7.232 7.214 7.168 7.135 7.117 6.924 6.904 6.758 6.461 6.441 3.755 3.727 3.687 1.331 1.224 9 8 7 6 5 4 3 2 1 ppm 8.000 4.033 1.068 1.109 3.944 4.677 2.124 7.886 1.958 1.882 1.911 19.876 17.936 18.224 S39
133.058 132.065 129.444 129.092 129.045 129.018 128.987 128.702 128.675 128.617 128.358 128.231 128.094 125.908 125.822 123.198 123.100 122.153 121.350 120.489 119.793 117.450 117.415 162.437 161.943 161.446 160.952 154.496 153.871 151.059 140.876 139.293 138.745 134.807 133.058 132.065 129.444 129.326 129.092 129.045 129.018 128.987 128.702 128.675 128.617 128.358 128.231 128.094 125.908 125.822 123.198 123.100 122.153 121.350 120.489 119.793 117.450 117.415 77.317 77.000 76.682 54.614 54.151 52.437 35.036 34.827 31.465 31.149 132 130 128 126 124 122 120 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S40
7.699 7.489 7.358 7.335 7.240 7.186 7.172 7.153 7.109 7.096 7.084 7.072 7.061 7.049 6.685 6.474 6.455 6.308 4.475 4.449 4.442 4.415 3.805 1.331 1.234 9 8 7 6 5 4 3 2 1 ppm 8.115 4.000 0.978 1.001 8.990 12.287 0.970 1.853 1.896 8.229 8.391 3.709 18.215 18.111 S41
131.326 130.463 129.439 128.918 128.826 128.713 128.475 125.912 125.775 123.204 123.014 122.142 121.291 120.496 119.605 117.415 162.442 161.947 161.452 160.957 153.247 152.393 151.034 141.552 138.934 137.308 134.812 131.326 130.463 129.439 128.918 128.826 128.713 128.475 125.912 125.775 123.204 123.014 122.142 121.291 120.496 119.605 117.415 77.318 77.000 76.683 73.881 54.050 52.530 34.981 34.834 31.474 31.175 130 128 126 124 122 120 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S42
7.693 7.486 7.469 7.375 7.248 7.240 7.229 7.211 7.171 7.153 7.134 7.052 6.800 6.742 6.727 6.153 6.133 3.781 3.749 3.722 3.690 3.653 3.607 1.335 9 8 7 6 5 4 3 2 1 ppm 8.000 5.088 1.028 2.074 1.998 3.896 9.626 1.829 1.761 1.770 4.236 6.235 7.880 2.231 35.816 S43
132.958 131.997 129.292 129.079 128.978 128.829 128.695 128.665 128.638 128.606 128.380 128.114 127.725 125.897 124.566 123.188 123.139 122.329 122.211 121.709 120.479 119.386 162.423 161.929 161.433 160.938 154.202 153.350 151.244 139.314 138.432 134.792 132.958 129.292 129.079 128.978 128.829 128.695 128.665 128.638 128.606 128.380 128.114 127.725 125.897 124.566 123.188 123.139 122.329 122.211 121.709 120.479 119.386 117.461 117.426 117.388 77.318 77.000 76.682 54.076 53.657 53.442 52.251 35.167 34.857 31.468 31.238 132 130 128 126 124 122 120 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S44
7.691 7.483 7.392 7.355 7.312 7.290 7.276 7.261 7.240 7.220 7.199 6.894 6.499 6.479 6.444 6.376 4.545 4.519 4.489 4.462 4.448 4.422 4.407 4.382 4.000 3.856 3.835 1.319 1.267 9 8 7 6 5 4 3 2 1 ppm 8.000 3.963 1.115 1.093 8.632 3.727 7.961 1.986 0.718 1.901 4.014 3.791 3.790 4.263 1.539 1.808 1.897 18.000 18.469 S45
131.279 130.542 129.724 129.179 128.995 128.712 128.683 128.622 128.392 127.502 125.912 124.813 123.287 123.203 122.188 121.339 120.495 119.576 117.453 117.415 117.376 162.440 161.943 161.448 160.952 153.763 152.069 151.061 141.551 138.890 137.871 137.317 134.805 131.279 130.542 129.724 129.179 128.995 128.712 128.683 128.622 128.392 127.502 125.912 124.813 123.287 123.203 122.188 121.339 120.495 119.576 117.453 117.415 117.376 77.318 77.000 76.682 73.511 73.477 54.132 52.596 35.064 34.840 31.472 31.168 132 130 128 126 124 122 120 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S46
7.716 7.504 7.382 7.358 7.240 7.222 7.205 7.146 7.128 6.692 3.718 1.151 9 8 7 6 5 4 3 2 1 ppm 8.015 3.999 3.886 2.131 4.042 8.012 4.008 16.000 36.068 S47
129.319 129.169 129.033 129.006 128.722 128.692 128.629 128.405 128.137 128.052 125.921 123.212 122.783 120.503 119.405 117.461 117.422 117.383 162.458 161.959 161.466 160.969 154.125 153.566 139.332 134.818 133.299 129.319 129.169 129.033 129.006 128.722 128.692 128.629 128.405 128.137 128.052 125.921 123.212 122.783 120.503 119.405 117.461 117.422 117.383 77.318 77.000 76.683 54.533 34.966 31.089 132 130 128 126 124 122 120 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S48
7.704 7.497 7.406 7.320 7.302 7.299 7.282 7.240 7.227 7.209 7.135 6.968 6.497 6.493 3.730 3.650 1.257 9 8 7 6 5 4 3 2 1 ppm 8.278 4.100 2.060 2.084 4.174 2.100 7.984 3.957 S49 8.000 8.090 35.998
129.325 129.143 128.941 128.726 128.700 128.671 128.642 128.409 127.906 127.756 125.908 123.199 122.666 120.491 118.189 117.452 117.413 117.373 162.439 161.943 161.446 160.952 153.810 152.944 139.494 139.116 134.800 132.576 129.325 129.143 128.941 128.726 128.700 128.671 128.642 128.409 127.906 127.756 125.908 123.199 122.666 120.491 118.189 117.452 117.413 117.373 77.318 77.000 76.682 53.636 53.281 35.073 31.197 132 130 128 126 124 122 120 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm S50
ITC measurements were performed using a MicroCal MCS calorimeter interfaced with a microcomputer. All sample solutions were carefully degassed prior to titration using the equipment provided with the instrument. A solution of the cyclophane 1 or 5 (CHCl3) was titrated into a solution of the threadlike salt 9 TFPB (CHCl3) using a 280-μL syringe. Each titration consisted of a preliminary 10-μL injection followed by 27 subsequent additions of 10 μl. The entropy (ΔS o ) of the complexation was determined by subtracting the heat of dilution of each titration from the enthalpy (ΔH o ) of the titration. All the experiments were performed at 298 K. MicroCal LLC software was used to compute the thermodynamic parameters of the titration based on the one-site binding model. The Gibbs free energy (ΔG o ) was calculated from the binding constant using R = 1.987 cal*k -1 *mol -1. Aliquouts (10 μl, 10 mm) of CHCl3 solution of the macrocycle 1 were titrated into stirring CHCl3 solution of the 9 TFPB (1 mm) at 298 K. Host M + Entry N K (M -1 ) ΔH o (cal*mol -1 ) ΔS o (cal*k -1 *mol -1 ) ΔG o (kcal*mol -1 ) 1 0.907 ± 0.00777 1.09E4 ± 6.13E2-6803 ± 79.08-4.34-5.50 ± 0.03 Threadlike Cyclophane 1 2 0.910 ± 0.00899 9.31E3 ± 5.43E2-7241 ± 102.9-6.12-5.41 ± 0.04 Salt 3 0.900 ± 0.00561 1.05E4 ± 4.05E2-7367 ± 65.78-6.31-5.48 ± 0.02 9 TFPB Average 0.906 ± 0.00759 1.02E4 ± 5.27E2-7137 ± 84.00-5.59 ± 1.09-5.47 ± 0.03 Aliquouts (10 μl, 20 mm) of CHCl3 solution of the cyclophane 5 were titrated into stirring CHCl3 solution of the 9 TFPB (2 mm) at 298 K. Host M + Entry N K (M -1 ) ΔH o (cal*mol -1 ) ΔS o (cal*k -1 *mol -1 ) ΔG o (kcal*mol -1 ) 1 0.912 ± 0.0193 2.48E3 ± 2.40E2-3636 ± 111.3 3.34-4.63 ± 0.06 Threadlike Cyclophane 5 2 0.930 ± 0.022 3.13E3 ± 3.67E2-3862 ± 134.3 3.04-4.77 ± 0.07 Salt 3 0.902 ± 0.014 1.93E3 ± 1.02E2-4009 ± 96.14 1.59-4.48 ± 0.03 9 TFPB Average 0.915 ± 0.0187 2.51E3 ± 2.60E2-3836 ± 114.99 2.66 ± 0.94-4.64 ± 0.06 S51
S52
S53
ITC measurements were performed using a MicroCal MCS calorimeter interfaced with a microcomputer. All sample solutions were carefully degassed prior to titration using the equipment provided with the instrument. A solution of the cyclophane 10 or 13 (CHCl3) was titrated into a solution of the threadlike salt 9 TFPB (CHCl3) using a 280-μL syringe. Each titration consisted of a preliminary 10-μL injection followed by 27 subsequent additions of 10 μl. The entropy (ΔS o ) of the complexation was determined by subtracting the heat of dilution of each titration from the enthalpy (ΔH o ) of the titration. All the experiments were performed at 298 K. MicroCal LLC software was used to compute the thermodynamic parameters of the titration based on the one-site binding model. The Gibbs free energy (ΔG o ) was calculated from the binding constant using R = 1.987 cal*k -1 *mol -1. Aliquouts (10 μl, 12 mm) of CHCl3 solution of the cyclophane 10 were titrated into stirring CHCl3 solution of the 9 TFPB (0.8 mm) at 298 K. Host M + Entry N K (M -1 ) ΔH o (cal*mol -1 ) ΔS o (cal*k -1 *mol -1 ) ΔG o (kcal*mol -1 ) 1 0.915 ± 0.085 1.29E3 ± 1.64E2-6937 ± 839.7-9.03-4.24 ± 0.08 Threadlike Cyclophane 10 2 0.901 ± 0.0551 1.37E3 ± 1.17E2-7521 ± 597.8-10.9-4.28 ± 0.05 Salt 3 0.925 ± 0.108 1.41E3 ± 2.19E2-6795 ± 1023-8.38-4.29 ± 0.10 9 TFPB Average 0.914 ± 0.0855 1.36E3 ± 1.72E2-7084 ± 838.4-9.44 ± 1.31-4.27 ± 0.08 Aliquouts (10 μl, 18 mm) of CHCl3 solution of the cyclophane 13 were titrated into stirring CHCl3 solution of the 9 TFPB (1.2 mm) at 298 K. Host M + Entry N K (M -1 ) ΔH o (cal*mol -1 ) ΔS o (cal*k -1 *mol -1 ) ΔG o (kcal*mol -1 ) 1 1.00 ± 0.139 7.8E2 ± 1.4E2-1547 ± 279.7 8.04-3.94 ± 0.12 Threadlike Cyclophane 13 2 1.00 ± 0.183 5.94E2 ± 1.25E2-1700 ± 406.4 6.99-3.78 ± 0.14 Salt 3 0.949 ± 0.103 7.67E2 ± 9.85E1-1633 ± 226.6 7.72-3.93 ± 0.08 9 TFPB Average 0.983 ± 0.145 7.14E2 ± 1.22E2-1627 ± 313.4 7.58 ± 0.54-3.89 ± 0.11 S54
S55
S56
S57
S58
Competition experiment for the cyclophane 1 and 5 with threadlike salt 9 TFPB a) b) c) 1 H NMR spectra (400 MHz, CDCl 3, 298 K) of a) an equimolar mixture (10 mm) of 1 and 9 TFPB, b) an equimolar mixture of 1, 5, and 9 TFPB, c) an equimolar mixture of 5 and 9 TFPB Complexation ratio for b) Tetraaza-cyclophane 1: δ δ(free) δ(shift) 3.776 3.726 = = = 76% δ(max) D 0.0655 Tetraoxo-cyclophane 5: δ δ(free) δ(shift) 4.520 4.506 = = = 23% δ(max) D 0.0609 S59
Competition experiment for the cyclophane 10 and 13 with threadlike salt 9 TFPB a) b) c) 1 H NMR spectra (400 MHz, CDCl 3, 298 K) of a) an equimolar mixture (10 mm) of 10 and 9 TFPB, b) an equimolar mixture of 10, 13, and 9 TFPB, c) an equimolar mixture of 10 and 9 TFPB Complexation ratio for b) Tetraaza-cyclophane 10: δ δ(free) δ(shift) 3.771 3.716 = = = 62% δ(max) D 0.0887 Tetraoxo-cyclophane 13: δ δ(free) δ(shift) 4.542 4.518 = = = 37% δ(max) D 0.0646 S60
(a) O H (b) N Ar H Ar N H (c) D R D R (d) D R N R H H N D R (e) R N H Ar-CH 2 -N 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 1 H NMR spectra (400 MHz, CDCl 3, 298 K) of an equimolar mixture of the threadlike salt 16-TFPB, the tetraaza-cyclophane 1, and the aldehyde 17 that had been heated at 323 K for (a) 0, (b) 10, (c) 30, (d) 90, and (e) 540 min. D and R denote signals representing the dumbbell-shaped salt and the [2]rotaxane, respectively. S61
S62
S63
S64
S65
[18] + = C 69 H 91 N 8 + = 1031.7361 S66
+TOF MS: 9 MCA scans from Sample 1 of 170601-chiu-YHC-Rtx233-3.wiff a=3.56484909623412740e-004, t0=4.06299435126857130e+001 R; (Nanospray) Max. 2.5e4 counts. I n t e n s i t y, c o u n t s 2.4e4 2.2e4 2.0e4 1.8e4 1.6e4 1.4e4 1.2e4 1.0e4 8000.0 6000.0 4000.0 2000.0 1035.6745 1036.6789 1037.6914 [19] + = C 69 H 87 N 4 O 4 + = 1035.6722 1032 1034 1036 1038 1040 1042 1044 1046 1048 1050 m/z, Da S67
+TOF MS: 12 MCA scans from Sample 1 of 170830-chiu-YHC-pNrtx-3.wiff a=3.56444304890517110e-004, t0=4.40480890316976000e+001 R; (Nanospray) Max. 2.3e4 counts. In te n s ity, c o u n ts 2.3e4 2.2e4 2.1e4 2.0e4 1.9e4 1.8e4 1.7e4 1.6e4 1.5e4 1.4e4 1.3e4 1.2e4 1.1e4 1.0e4 9000.0 8000.0 7000.0 6000.0 5000.0 4000.0 3000.0 2000.0 1000.0 0.0 597.0287 [20] + = C 69 H 91 N 8 + = 1031.7361 1031.7348 1033.7480 600 650 700 750 800 850 900 950 1000 1050 1100 m/z, Da S68
+TOF MS: 13 MCA scans from Sample 1 of 170714-chiu-YJL-4074-2threasing-p-O-rtx-3.wiff a=3.56638477167076360e-004, t0=7.13464503634531870e+001 (Nanospray) Max. 1.4e4 counts. I n t e n s i t y, c o u n t s 1.4e4 1.3e4 1.2e4 1.1e4 1.0e4 9000.0 8000.0 7000.0 6000.0 5000.0 4000.0 3000.0 2000.0 1000.0 0.0 1035.6759 1036.6820 1037.6907 [21] + = C 69 H 87 N 4 O 4 + = 1035.6722 1030 1032 1034 1036 1038 1040 1042 1044 1046 m/z, Da S69
[23] + = C 61 H 82 N 7 + = 912.6626 S70
[24] + = C 61 H 82 N 7 + = 912.6626 S71