Formation and Properties of Cyclo[6]pyrrole and Cyclo[7]pyrrole. Thomas Köhler, Daniel Seidel, Vincent Lynch, Forrest O. Arp, Zhongping Ou, Karl M. Kadish, * and Jonathan L. Sessler *. Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, The University of Texas, 1 University Station A5430, Austin, TX, 78712-0165. Department of Chemistry, The University of Houston, Houston, TX, 77204-5003. Supporting Information I Synthetic Experimental, including relevant UV-visible spectra. II X-ray Experimental III Cyclovoltammetric Experimental I Synthetic Experimental: All solvents and chemicals were obtained commercially and used as received. The bipyrrolic precursor was prepared as described previously ( J. L. Sessler, and M. C. Hoehner, Synlett 1994, 211). Proton and 13 C-NMR spectra were measured at 25 ºC a Varian Unity Innova at 500 MHz. UV-vis spectra were recorded on a BECKMAN DU 640B spectrophotometer. High resolution CI mass spectra were obtained on a VG ZAB2-E mass spectrometer. S 1
A 1 L round bottom flask was charged with a stir bar, 500 ml of dichloromethane, and a solution of 2.7 goffecl 3 6H 2 O (10 mmol) in 100 ml of 1 M hydrochloric acid. The resulting biphasic mixture was stirred at 300 RPM, while the bipyrrole 2 (S 1, 1 mmol), dissolved in 50 ml of dichloromethane, was added slowly via syringe pump over a period of 14 hours, with the needle submerged into the organic phase. For slow continuous additions, a Sage syringe pump (model M365) was employed. After completion of the addition, the reaction mixture was stirred for 5 more hours. The phases were not dried over sodium sulfate but the solvent immediately removed in vacuo. The crude dark green product was purified via column chromatography on silica gel using dichloromethane containing 0.5% methanol as the eluent to yield a hazelnut brown band of cyclo[6]pyrrole 3. Increasing the polarity of the solvent system to 2% methanol yielded a yellow brown band of cyclo[8]pyrrole 1. Further increasing the polarity to 7.5% methanol in dichloromethane afforded a grass green band consisting of cyclo[7]pyrrole 4. The solvent was removed in vacuo and the residues recrystallized from dichloromethane/hexanes to yield the corresponding bis hydrochloride salts of 1, 3, and4 as dark microcrystalline powders. 2,3,6,7,10,11,14,15,18,19,22,23-Dodecaethyl[22]hexaphyrin(0.0.0.0.0.0) (3) 15% yield; 1 H-NMR (500 MHz, CDCl 3 ) δ [ppm] -1.34 (s, 6H, NH), 1.93 (t, J HH = 7.5 Hz, 36H, CH 2 CH 3 ), 4.24 (q, J HH = 7.5 Hz, 24H, CH 2 CH 3 ); 13 C-NMR (125 MHz, CDCl 3 ) δ [ppm] 17.92, 21.86, 126.82, 134.49; HRMS (CI): m/z 726.5351 ((M-HCl 2 )+H + ), calcd for C 48 H 66 N 6 726.5349. UV-vis (CH 2 Cl 2 ) λmax [nm] (ε in mol -1 cm -1 ) 397 (122 600), 708, 792 (206 400). 2,3,6,7,10,11,14,15,18,19,22,23,26,27-Tetradecaethyl[26]heptaphyrin(0.0.0.0.0.0.0) (4) 5% yield; 1 H-NMR (500 MHz, CDCl 3 ) δ [ppm] -2.12 (s, 7H, NH), 1.80 (t, J HH = 7.5 Hz, 42H, CH 2 CH 3 ), 4.26 (q, J HH = 7.5 Hz, 28H, CH 2 CH 3 ); 13 C-NMR (125 MHz, CDCl 3 ) δ [ppm] 16.78, 21.63, 126.17, 131.37; HRMS (CI): m/z 883.6003 ((M- Cl)+H + ), calcd for C 56 H 78 N 7 Cl 883.6007. UV-vis (CH 2 Cl 2 ) λmax [nm] (ε in mol -1 cm -1 ) 429 (44 300), 936 (66700). 2,3,6,7,10,11,14,15,18,19,22,23,26,27,30,31-Hexadecaethyl[30]octaphyrin(0.0.0.0.0.0.0.0) (1) 25% yield; 1 H- NMR (500 MHz, CDCl 3 ) δ [ppm] -0.38 (s, 8H, NH), 1.60 (t, J HH = 7.5 Hz, 48H, CH 2 CH 3 ), 4.00 (bs, 32H, CH 2 CH 3 ); 13 C-NMR (125 MHz, CDCl 3 ) δ [ppm] 15.82, 21.20, 126.32, 128.77; HRMS (CI): m/z 969.7220 ((M- Cl 2 )+H + ), calcd for C 64 H 89 N 8 969.7210. UV-vis (CH 2 Cl 2 ) λmax [nm] (ε in mol -1 cm -1 ) 429 (65 100), 976, 1098 (87 600) [estimate only since this max lies near the spectrophotometer limit value due close to the window limit]. To obtain the free base species of cyclo[n]pyrroles 1, 3, and 4, respectively: The acid salts are dissolved in methylene chloride and washed three times with 1M NaOH. S 2
UV/Vis/NIR spectrum of Cyclo{6}pyrrole 3 0,9 0,8 0,7 0,6 Absorbance 0,5 0,4 0,3 Cyclo[6] bis HCl-salt Cyclo[6] Free Base 0,2 0,1 0 350 450 550 650 750 850 950 1050 Wavelength (nm) N N H HN *2HCl N H N N n 3: n=1 Fig. 1 : UV/Vis spectra of 3 and its free base. S 3
UV/Vis/NIR Spectrum of Cyclo[7]pyrrole 4 0.6 0.5 0.4 Absorbance 0.3 Cyclo[7]pyrrole Bis HCl-salt Cyclo[7]pyrrole Free Base 0.2 0.1 0 350 450 550 650 750 850 950 1050 Wavelength (nm) N N H HN * 2 HCl N H N N n 4: n = 2 Fig. 2 : UV/Vis spectra of 4 and its free base. S 4
II X-ray Experimental Data: X-ray Experimental for C 48 H 66 N 6-2C 2 F 3 O 2, 3a: Crystals grew as very dark plates and prisms by vapor diffusion of hexanes into a methylene chloride solution of the macrocycle in the presence of trifluoroacetic acid. The data crystal was cut from a larger crystal and had approximate dimensions; 0.31 x 0.26 x 0.14 mm. The data were collected on a Nonius Kappa CCD diffractometer using a graphite monochromator with MoK radiation ( = 0.71073 Å). A total of 478 frames of data were collected using -scans with a scan range of 1 and a counting time of 110 seconds per frame. The data were collected at 153 K using an Oxford Cryostream low temperature device. Details of crystal data, data collection and structure refinement are listed in Table 1. Data reduction were performed using DENZO-SMN. 1 The structure was solved by direct methods using SIR92 2 and refined by full-matrix least-squares on F 2 with anisotropic displacement parameters for the non-h atoms using SHELXL-97. 3 The hydrogen atoms on carbon were calculated in ideal positions with isotropic displacement parameters set to 1.2xUeq of the attached atom (1.5xUeq for methyl hydrogen atoms). The hydrogen atom positions on the pyrrole nitrogen atoms were observed in a F map and refined with isotropic displacement parameters. The function, w( F o 2 - F c 2 ) 2, was minimized, where w = 1/[( (F o )) 2 + (0.0437*P) 2 + (0.5418*P)] and P = ( F o 2 + 2 F c 2 )/3. R w (F 2 ) refined to 0.121, with R(F) equal to 0.0506 and a goodness of fit, S, = 1.04. Definitions used for calculating R(F), R w (F 2 ) and the goodness of fit, S, are given below. 4 The data were corrected for secondary extinction effects. The correction takes the form: F corr = kf c /[1 + (3.2(3)x10-5 )* F c 2 3 /(sin2 )] 0.25 where k is the overall scale factor. Neutral atom scattering factors and values used to calculate the linear absorption coefficient are from the International Tables for X-ray Crystallography (1992). 5 All figures were generated using SHELXTL/PC. 6. S 5
References 1) Otwinowski Z.;Minor W. In DENZO-SMN., Methods in Enzymology, 276: Macromolecular Crystallography, part A, 307 326, C. W. Carter, Jr. and R. M. Sweet, Eds.; Academic Press 1997. 2) Altomare, A.; Cascarano, G.; Giacovazzo, C; Guagliardi, A. SIR92. A program for crystal structure solution. J. Appl. Cryst. 26, 1993, 343-350. 3) Sheldrick, G. M. SHELXL97 Program for the Refinement of Crystal Structures; 1994; University of Göttingen, Germany. 4) Rw(F 2 ) = { w( Fo 2 - Fc 2 ) 2 / w( Fo ) 4 } 1/2 where w is the weight given each reflection. R(F) = ( Fo - Fc )/ Fo } for reflections with Fo > 4( (Fo)). S = [ w( Fo 2 - Fc 2 ) 2 /(n - p)] 1/2, where n is the number of reflections and p is the number of refined parameters 5) International Tables for X-ray Crystallography. Vol. C, Tables 4.2.6.8 and 6.1.1.4, A. J. C. Wilson, editor, Boston: Kluwer Academic Press 1992. 6) Sheldrick, G. M.; SHELXTL/PC (Version 5.03), 1994. Siemens Analytical X-ray Instruments, Inc., Madison, Wisconsin, USA. Crystal data and structure refinement for 3a: Empirical formula C52 H66 F6 N6 O4 Formula weight 953.11 Temperature 153(2) K Wavelength 0.71073 Å Crystal system Triclinic Space group P-1 Unit cell dimensions a = 10.9346(4) Å = 64.377(2). b = 11.0747(4) Å = 74.543(2). c = 11.5478(4) Å = 89.209(2). Volume 1206.97(7) Å 3 Z 1 Density (calculated) 1.311 g/cm 3 S 6
Absorption coefficient 0.099 mm -1 F(000) 506 Crystal size 0.31 x 0.26 x 0.14 mm Theta range for data collection 2.99 to 27.50. Index ranges -14<=h<=14, -14<=k<=14, -15<=l<=14 Reflections collected 9461 Independent reflections 5381 [R(int) = 0.0264] Completeness to theta = 27.50 97.0 % Absorption correction None Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 5381 / 0 / 320 Goodness-of-fit on F 2 1.039 Final R indices [I>2sigma(I)] R1 = 0.0506, wr2 = 0.1089 R indices (all data) R1 = 0.0747, wr2 = 0.1210 Extinction coefficient 3.2(3)x10-5 Largest diff. peak and hole 0.22 and -0.30 e.å -3 Fig. 3: View of 3a showing partial atom labeling scheme. Displacement ellipsoids are scaled to the 50% probability level. Most hydrogen atoms have been removed for clarity. Dashed lines are indicative of H-bonding interactions. The complex lies on a crystallographic inversion center at ½, ½, ½. Atoms with labels appended by are related by 1-x, 1-y, 1-z. S 7
Fig. 4: Unit cell packing diagram for 1. The view is approximately down the a axis. Dashed lines are indicative of H-bonding interactions. X-ray Experimental for [C 56 H 77 N 7 ] 2+ 2Cl - - H 2 O 2C 6 H 6, 4a: Crystals grew as dark green needles by vapor diffusion of hexanes into a benzene solution of the macrocycle. The data crystal was a long needle that had approximate dimensions; 0.39x0.06x0.05 mm. The data were collected on a Nonius Kappa CCD diffractometer using a graphite monochromator with MoK radiation ( = 0.71073 Å). A total of 299 frames of data S 8
were collected using -scans with a scan range of 1 and a counting time of 243 seconds per frame. The data were collected at 153 K using an Oxford Cryostream low temperature device. Details of crystal data, data collection and structure refinement are listed in Table 1. Data reduction were performed using DENZO-SMN. 1 The structure was solved by direct methods using SIR92 2 and refined by full-matrix least-squares on F 2 with anisotropic displacement parameters for the non-h atoms using SHELXL-97. 3 The hydrogen atoms on carbon were calculated in ideal positions with isotropic displacement parameters set to 1.2xUeq of the attached atom (1.5xUeq for methyl hydrogen atoms). The hydrogen atoms on the pyrrole nitrogen atoms were observed in a F map and refined with isotropic displacement parameters. The hydrogen atoms on the water molecule were also observed in a F map. Attempts to refine their positions and displacement parameters proved unsatisfactory. In the final refinement cycles, the O-H bond lengths were idealized to 0.80 Å by sliding the H atom along the O-H bond vector. The isotropic displacement parameters were set to 1.2xUeq for O1W. The function, w( Fo 2 - Fc 2 ) 2, was minimized, where w = 1/[( (Fo)) 2 + (0.0581*P) 2 + (1.9786*P)] and P = ( Fo 2 + 2 Fc 2 )/3. Rw(F 2 ) refined to 0.198, with R(F) equal to 0.0787 and a goodness of fit, S, = 1.00. Definitions used for calculating R(F),Rw(F 2 ) and the goodness of fit, S, are given below. 4 The data were corrected for secondary extinction effects. The correction takes the form: Fcorr = kfc/[1 + (2.2(6)x10-6 )* Fc 2 3 /(sin2 )] 0.25 where k is the overall scale factor. Neutral atom scattering factors and values used to calculate the linear absorption coefficient are from the International Tables for X-ray Crystallography (1992). 5 All figures were generated using SHELXTL/PC. 6 References 1) Otwinowski Z.;Minor W. In DENZO-SMN., Methods in Enzymology, 276: Macromolecular Crystallography, part A, 307 326, C. W. Carter, Jr. and R. M. Sweet, Eds.; Academic Press 1997. S 9
2) Altomare, A.; Cascarano, G.; Giacovazzo, C; Guagliardi, A. SIR92. A program for crystal structure solution. J. Appl. Cryst. 26, 1993, 343-350. 3) Sheldrick, G. M. SHELXL97 Program for the Refinement of Crystal Structures; 1994; University of Göttingen, Germany. 4) Rw(F 2 ) = { w( Fo 2 - Fc 2 ) 2 / w( Fo ) 4 } 1/2 where w is the weight given each reflection. R(F) = ( Fo - Fc )/ Fo } for reflections with Fo > 4( (Fo)). S = [ w( Fo 2 - Fc 2 ) 2 /(n - p)] 1/2, where n is the number of reflections and p is the number of refined parameters 5) International Tables for X-ray Crystallography. Vol. C, Tables 4.2.6.8 and 6.1.1.4, A. J. C. Wilson, editor, Boston: Kluwer Academic Press 1992. 6) Sheldrick, G. M.; SHELXTL/PC (Version 5.03), 1994. Siemens Analytical X-ray Instruments, Inc., Madison, Wisconsin, USA. Crystal data and structure refinement for 4a. Empirical formula C68 H91 Cl2 N7 O Formula weight 1093.38 Temperature 153(2) K Wavelength 0.71073 Å Crystal system Triclinic Space group P-1 Unit cell dimensions a = 10.7430(4) Å = 99.666(2). b = 11.5435(5) Å = 98.104(2). c = 26.1232(12) Å = 104.904(2). Volume 3027.9(2) Å 3 Z 2 Density (calculated) 1.199 g/cm 3 Absorption coefficient 0.156 mm -1 F(000) 1180 Crystal size 0.39 x 0.06 x 0.05 mm Theta range for data collection 3.00 to 25.00. S 10
Index ranges -12<=h<=12, -12<=k<=13, -28<=l<=30 Reflections collected 16734 Independent reflections 10386 [R(int) = 0.0871] Completeness to theta = 25.00 97.5 % Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 10386 / 0 / 732 Goodness-of-fit on F 2 1.004 Final R indices [I>2sigma(I)] R1 = 0.0787, wr2 = 0.1499 R indices (all data) R1 = 0.2175, wr2 = 0.1980 Extinction coefficient 2.2(6)x10-6 Largest diff. peak and hole 0.484 and -0.410 e.å -3 Figure 5. View of 4a showing the atom labeling scheme. Displacement ellipsoids are scaled to the 50% probability level. Most hydrogen atoms have been removed for clarity. Dashed lines are indicative of H-bonding interactions. S 11
Fig. 6: Unit cell packing diagram for 4a. The view is approximately down the a axis. The benzene solvate molecules are shown in wireframe form. S 12
III Cyclic Voltammetric Experimental Cyclic voltammetry was carried out with an EG&G model 173 potentiostat. A threeelectrode system was used and consisted of a glassy carbon working electrode, a platinum wire counter electrode, and a saturated calomel reference electrode (SCE). The SCE was separated from the bulk of the solution by a fritted-glass bridge of low porosity which contained the solvent/supporting electrolyte mixture. a) Cyclo[6]pyrrole -0.48 0.95-0.35 b) Cyclo[7]pyrrole 1.56 0.67-0.18 1.10 c) Cyclo[8]pyrrole 0.77 0.52-0.08 1.30 1.14 Potential (V vs SCE) Figure 7: Cyclic voltammograms of cyclo[6]pyrrole 3, cyclo[7]pyrrole 4 and cyclo[8]pyrrole 1 in CH 2 Cl 2,0.1 M tetrabutylammonium perchlorate at a scan rate of 0.1 V/s. S 13