NMR spectra were recorded on Bruker DRX 500 (500.1 MHz for 1H, 125.7 MHz for 13C), AM 400 or DRX 400 (400.1 MHz for 1H, 100.6 MHz or 13C), DPX 250 or AC 250 (250.1 MHz for 1H, 62.9 MHz for 13C) instruments. Chemical shifts are quoted in parts per million with respect to TMS. Mass spectra were recorded on Kratos MS-50 (FAB), VG BioQ (ES), Kratos MS890 (FAB, EI), Kratos Kompact MALDI IV, Bruker BioApex II (ES), Micromass Quattro (ES) and Micromass Q-TOF (ES) instruments. Solution and solid state infrared spectra were recorded on a Perkin Elmer Paragon 1000 FTIR spectrometer at 4cm-1 resolution or better.
Reflection - adsorption infrared spectra were recorded at ThermoUnicam (Cambridge) on a Mattson Infinity Series FTIR spectrometer with an external sample module fitted with a liquid nitrogen cooled MCT detector and SpectraTech variable angle reflection accessory set to 83°. 2048 scans were recorded at a resolution of 4 cm-1.
X-ray photoelectron spectroscopy was performed with a VG ESCALAB 200D instrument at ICI Runcorn Heath. Unmonochromated Mg Ka radiation was used with a photoelectron takeoff angle of 90°. Binding energies were calibrated to the Au 4f7/2 peak at 83.98 eV. Spectral acquisition and processing was controlled with the Eclipse software. Alternatively spectra were recorded on a Scienta ESCA300 spectrometer at Daresbury Laboratory.
Contact mode atomic force microscopy was carried out with either a Digital Instruments (DI) Nanoscope III or East Coast Scientific microscope. Oxide sharpened silicon nitride cantilevers (DI) with a nominal force constant of 0.12 Nm-1 were used to acquire the images of appendix 4.
Scanning tunnelling microscopy was performed with an Omicron Micro H/LH microscope with SCALA control system and software at the School of Physics and Astronomy, University of Birmingham. A mechanically cut Pt/Ir tip was used. The gold on mica sample was affixed to the steel sample plate by spot welding with Ta foil. Imaging at above room temperature was performed in a vacuum chamber at a pressure of < 5 ´ 10-7 mbar.
Contact angles and electrochemical measurements were carried out at the Laboratory of Supramolecular Chemistry and Technology, University of Twente.
Advancing and receding water contact angles were recorded with a Krüss contact angle goniometer using the sessile drop method. Angles were calculated by the G40 software (Krüss) by automatic analysis of images of the drop as it was slowly advanced or receded on the sample.
Electrochemistry was carried out in a 3 electrode cell in which the gold sample comprised the working electrode with a geometric area of 0.44 cm2. A Pt disc was used as a counter electrode with a Hg/Hg2SO4 reference electrode with KCl salt bridge solution (Radiometer). Potentials are quoted with respect to this electrode. Experiments were controlled by an Autolab potentiostat and frequency response analyser (EcoChemie BV) interfaced to a computer running the GPES 4.5 and FRA software. The differential double layer capacitance was measured by cyclic voltammetry in 0.1 M NaClO4 aqueous solution, scanning over the range -0.3 - –0.4 V at rates of 0.1, 0.2 and 0.5 Vs-1. The capacitance was calculated as the sum of the current at –0.35 V in both scan directions divided by 2 ´ scan rate ´ geometric electrode area. Heterogeneous electron transfer between the modified electrodes and the external redox couple Fe(CN)63-/4- was measured by cyclic voltammetry in a solution 1 mM in both K3Fe(CN)6 and K4Fe(CN)6 and 0.1 M in K2SO4 scanning over the range 0 - –7 V at 0.1 Vs-1. The solution was purged with N2 prior to measurement. Faradaic impedance spectra were recorded using the same electrolyte solution. A sinusoidal excitation of 5 mV was applied to the open cell potential of –0.2 V. Impedance was measured at 40 frequencies between 0.1 Hz and 10 kHz. The spectra were analysed with the program Equivalent Circuit (B. A. Boukamp, University of Twente).
All glassware and glass slides used for preparation of monolayer were cleaned by one of two procedures. Procedure 1) Rinsing in acetone, sonication for 45 min in a 2 % solution of Decon 75, extensive rinsing with distilled water, sonication (45 min) in HPLC grade isopropanol, followed by sonication in ultrapure water for a further 45 min then drying under a stream of nitrogen or 2) Immersion in freshly prepared piranha solution (conc. H2SO4/30 % H2O2, 7/3) (caution - reacts violently with organic material. Contact with metals may cause rapid decomposition) followed by rinsing extensively with distilled water and finally with ultrapure water.
Preparation of gold substrates
Gold (99.99 %) was supplied by Birmingham Metals or Goodfellow Ltd.
(i) For RAIRS and microcontact printing. Substrates for reflection adsorption IR spectroscopy were prepared by Mr. R. Nelson by thermal evaporation of ~50 Å Cr and ~1000 Å of gold onto glass microscope slides using an Edwards evaporator. Substrates for microcontact printing were prepared in the same way, except using a silicon wafer instead of glass slides. The wafer was cleaved with a diamond stylus after evaporation of the gold.
(ii) For XPS. Gold substrates were prepared using a Balzers evaporator. Freshly cleaved mica was preheated to 300 °C for 20 h in vacuo. 1000 Å Au was evaporated at a rate of 10 Ås-1 onto the heated mica, which was annealed for 6 h at 300 °C followed by cooling in vacuo. The pressure in the chamber prior to evaporation was typically ~1 ´ 10-7 mbar. Substrates for STM were prepared similarly but using a home built evaporator.
(iii) For contact angle and electrochemical measurements. Gold substrates prepared by electron beam evaporation of Ti (5 nm) and Au (200 nm) onto 25 mm diameter glass discs were supplied by H. Krabbe (University of Twente). These were stored under nitrogen in Fluoroware containers and cleaned prior to use by treatment with oxygen plasma for 5 min followed by soaking in EtOH for 10 min.462
Typical monolayer preparations. Freshly evaporated or plasma cleaned gold substrates were immersed into a solution of thiol or disulfide at a concentration of 0.1 - 1 mM for ~12 h at room temperature. THF was used as a solvent for porphyrins. EtOH was used for non-porphyrin compounds. Care was taken to minimize exposure of the porphyrin solutions to light. After incubation samples were rinsed extensively with the same solvents before blowing dry with a stream of nitrogen.
Microcontact printing was carried out using a PDMS stamp prepared by Dr. W. T. S. Huck. After application of a 10 mM solution of mercaptoundecanoic acid in EtOH to the stamp using a filter paper, followed by blowing dry with nitrogen, the stamp was placed in contact with a gold substrate for several seconds. After removal of the stamp the sample was immersed into a solution of another thiol/disulfide (1 mM) for 4 min, before rinsing and blowing dry.
UV/visible titrations. For measurement of binding constants of sulfur/selenium ligands to 118, a 3.0 mL aliquot of a 4 mM solution of 118·MeOH in DCM/MeOH (200 mL MeOH per 100 mL of solvent) at 25 °C was titrated with 10 mL aliquots of a 75 mM solution of ligand in the same solvent mixture. The cuvette was magnetically stirred for ~30 s prior to recording each spectrum. Spectra were analysed with the program Specfit.257
1H NMR titrations. Typically a solution of 118·MeOH (4 mg) in CDCl3 (600 mL) was titrated with 5 mL aliquots of a solution of ligand in CDCl3 at a concentration of 72 mM. Spectra were acquired at room temperature. CDCl3 was stored over anhydrous K2CO3 in a refrigerator.
Prior to binding studies, EtSH, Me2S and Me2Se2 were filtered through neutral alumina, DMSO was filtered through CaH2 then neutral alumina, Ph2S and Ph2SO were distilled with a Kugelrohr apparatus.
X-ray crystallography. Diffraction data were collected on a Rigaku R-Axis IIc or Nonius Kappa CCD device. Data for small crystal were collected at the Daresbury SRS, Station 9.8 using a Bruker AXS SMART CCD area-detector, or at the ESRF (Grenoble). Structures were solved with either SHELXS-97 or SIR92.463-465 Refinement was carried out with SHELXL-97.463
THF, hexane, EA and Et2O were distilled before use. When stated as anhydrous, solvents were distilled from an appropriate drying agent immediately prior to use. Et3N was freshly distilled from CaH2, or stored over KOH pellets. 3-Picoline was distilled from KOH pellets under N2. Technical grade thionyl chloride was purified by distillation from triphenyl phosphite. Ultrapure water was obtained from a Millipore or Elgastat water purification system. Melting points were determined on a Gallenkamp melting point apparatus and are uncorrected.
Merck or Fluorochem 60 mesh silica gel was used for column chromatography. Merck silica was used for preparations involving rhodium porphyrins unless stated otherwise.
Benzyl-5-methyl-4-hexyl-3-methyl-pyrrole-2-carboxylate, trimethylsilyl-acetylene, 3,5-diiodobenzyl alcohol and 4-pyridyl-trimethyl-stannane were provided by Mr. C. Sporikou. 3-Trimethylsilylethynyl-benzaldehyde and 3,5-di-tert-butyl-benzaldehyde were provided by Dr. S. L. Darling. All other chemicals were purchased as reagent grade or better and used without further purification unless specified otherwise.
General procedure for porphyrin synthesis
The general porphyrin synthesis procedure is illustrated for 117. Other symmetrical porphyrins were prepared by substituting an alternative aldehyde for benzaldehyde. Unsymmetrical porphyrins were prepared by a statistical reaction using an equimolar mixture of two aldehydes. The purification of each compound is described separately.
116 (1.00 g, 1.64 mmol) and Pd/C (10 %, 0.10 g) were mixed then THF (50 mL) and Et3N (2 mL) added. The mixture was degassed then stirred under an atmosphere of H2 for 1 h. After filtration through celite, the solvents were removed and the grey solid (5,5'-carboxy-3,3'-dihexyl-4,4'-dimethyl-2,2'-dihydropyrrin) dried in vacuo. To this was added by cannula cold (~0 °C) degassed TFA (20 mL). After stirring for 10 min at 0 °C and 30 min at rt, with periodic exposure to vacuum to remove evolved CO2, the yellow solution was cooled to -20 °C. A degassed solution of benzaldehyde (166 mL, 1.63 mmol) in THF (50 mL) was added and the solution stirred under N2 for 3 h allowing the temperature to increase from -20 °C to -10 °C. DDQ (0.48 g, 2.11 mmol) was added and the green solution stirred for 15 min at rt. Et3N (40 mL) was added cautiously, followed by CHCl3 (200 mL). The brown solution was washed with water (100 mL portions) until the aqueous washings were colourless, the organic phase dried (MgSO4), and evaporated. The resulting dark coloured solids were dried in vacuo.
General procedure for Zn metallation of porphyrins
Zn metallation was carried out by boiling a solution of free-base porphyrin in chloroform and ~5 % MeOH with excess Zn(OAc)2·2H2O or Zn(OAc)2 for several minutes. The solution was filtered, washed with water, dried (MgSO4) and evaporated.
General procedure for Ni metallation of porphyrins
The free-base porphyrin in mixed CHCl3/MeOH solvent was refluxed under N2 with excess (>5 eq) Ni(OAc)2·4H2O overnight. After cooling the solution was filtered, washed with water, dried (MgSO4) and evaporated.
5-Acetoxymethyl-4-hexyl-3-methyl-1H-pyrrole-2-carboxylic acid benzyl ester (115)228
Pb(OAc)4 (28.35 g, 64 mmol) was added gradually with stirring over a 15 min period to a solution of benzyl-5-methyl-4-hexyl-3-methyl-pyrrole-2-carboxylate (20 g, 64 mmol) in glacial acetic acid (200 mL). After stirring for 2 h at rt under argon, the solvent was evaporated to produce an orange solid. The solids were extracted with CHCl3 (250 mL), filtered to remove undissolved material, the solution was washed with water (5 ´ 100 mL), dried (MgSO4), and evaporated to a brown solid. Recrystallization from MeOH afforded the pure product as a white solid (10.2 g, 43 %). Rf 0.7 (hexane/EA, 3/1).
1H NMR (250 MHz, CDCl3): d 9.02 (br s, 1H, NH), 7.44 - 7.28 (m, 5H, Ar), 5.30 (s, 2H, CH2Ph), 5.00 (s, 2H, CH2OAc), 2.41 (t, J = 7 Hz, 2H, hex H1), 2.27 (s, 3H, O2CCH3), 2.05 (s, 3H, CH3), 1.44 - 1.28 (m, 8H, hex H2-5), 0.87 (t, J = 7 Hz, 3H, hex H6); Anal. Calcd for C22H29NO4: C 71.13, H 7.87, N 3.77. Found: C 71.28, H 7.89, N 3.92.
5,5'-Dibenzyloxycarbonyl-3,3'-dihexyl-4,4'-dimethyl-2,2'-dihydropyrrin (116)228
Conc. HCl (4 mL) was added to a solution of 115 (10.24 g, 27 mmol) in warm MeOH (70 mL) and refluxed under argon for 3 h. After cooling to rt, water (70 mL) was added and the solution extracted with DCM (3 ´ 120 mL). The combined organic extracts were washed with satd. Na2CO3 (50 mL), dried (MgSO4) and evaporated to an orange solid. Recrystallization twice from MeOH yielded the pure product as pale yellow needles (6.77 g, 40 %). Rf 0.55 (hexane/EA, 3/1).
1H NMR (250 MHz, CDCl3): d 8.99 (s, 2H, NH), 7.35 - 7.23 (m, 10H, Ar), 5.22 (s, 4H, CO2CH2), 3.79 (s, 2H, CH2), 2.35 (t, J = 7 Hz, 4H, hex H1), 2.26 (s, 6H, CH3), 1.35 - 1.25 (m, 16H, hex H2-5), 0.87 (t, J = 7 Hz, 6H, hex H6); Anal. Calcd for C39H50N2O4: C 76.69, H 8.25, N. 4.59. Found: C 76.72, H 8.30, N 4.74.
2,8,12,18-Tetrahexyl-3,7,13,17-tetramethyl-5,15-diphenyl-porphyrin (117)
Purified by passing through a short silica column, eluted with hexane/EA (10/1), followed by recrystallization twice from CHCl3 layered with MeOH. Purple needles (489 mg, 70 %). Rf 0.75 (hexane/EA, 5/1).
Crystals were for structure determination were grown from toluene solution layered with MeOH, or from CHCl3 layered with a solution of 4-bromophenol in MeOH.
1H NMR (400 MHz, CDCl3): d 10.23 (s, 2H meso), 7.57 (d, J = 7 Hz, 4H, Ar), 7.81-7.71 (m, 6H, Ar), 3.97 (t, J = 8 Hz, 8H, hex H1), 2.48 (s, 12H, CH3), 2.18 (m, 8H, hex H2), 1.72 (m, 8H, hex H3), 1.48 (m, 8H, hex H4), 1.34 (m, 8H, hex H5), 0.89 (t, J = 7 Hz, 12H, hex H6), -2.40 (s, 2H, NH); 13C NMR (100.6 MHz, CDCl3): d 145.1, 143.3, 142.4, 141.4, 136.2, 133.0, 128.2, 127.6, 117.9, 96.9, 33.3, 32.0, 30.0, 26.8, 22.8, 14.6, 14.1; UV/vis (DCM): lmax 400, 506, 540, 574, 626 nm; FAB MS: m/z [M+H]+ calcd 855.6299, found 855.6302; IR (CCl4): nmax 2957 (s), 2929 (s), 1467 (m), 1444 (m) cm–1; Anal. Calcd for C60H78N4: C 84.26, H 9.19, N 6.55. Found C 84.04, H 9.17, N 6.45.
2,8,12,18-Tetrahexyl-3,7,13,17-tetramethyl-5,15-diphenyl-porphyrinato rhodium(III) iodide (118)
117 (200 mg, 0.23 mmol) and anhydrous NaOAc (96 mg, 1.17 mmol) were dissolved in DCM (anhydrous, 50 mL). The solution was degassed, and to this was added a solution of Rh2(CO)4Cl2 (160 mg, 4.12 mmol) in degassed DCM (20 mL) dropwise over 80 min. After stirring for 150 min at rt under N2, iodine (147 mg, 0.58 mmol) was added and stirring continued for a further 30 min. The solution was washed with aqueous KI (30 mL), and water (100 mL portions) until the washings were colourless. The organic phase was dried (MgSO4) and evaporated to a brown solid. Column chromatography (hexane/DCM, 1/1) afforded the product as a deep orange solid (225 mg, 89 %). Rf 0.6 (hexane/DCM, 1/1)
The product could be obtained as black crystals of the MeOH complex by recrystallization from DCM or CHCl3 layered with MeOH. Crystals of 118·MeOH for structure determination were obtained from a DCM solution layered with MeOH. Crystals of unsolvated 118 were obtained from a solution of 118 in DCM layered with ethylene glycol.
1H NMR (400 MHz, CDCl3): d 10.29 (s, 2H, meso), 8.13 (d, J = 7 Hz, 2H, Ar), 7.94 (d, J = 7 Hz, 2H, Ar), 7.80 - 7.67 (m, 6H, Ar), 4.04 (m, 4H, hex H1), 3.87 (m, 4H, hex H1), 2.47 (s, 12H, CH3), 2.17 (m, 8H, hex H2), 1.73 (m, 8H, hex H3), 1.48 (m, 8H, hex H4), 1.38 (m, 8H, hex H5), 0.90 (t, J = 7 Hz, 12H, hex H6); 13C NMR (100.6 MHz, CDCl3): d 144.4, 142.5, 141.5, 141.3, 138.9, 133.2, 133.0, 128.4, 127.7, 127.4, 121.2, 100.7, 33.1, 32.0, 30.0, 26.9, 22.8, 15.5, 14.1; UV/vis (DCM): lmax 402, 548, 522 nm; FIB MS: m/z [M+H]+ calcd 1105.4062, found 1105.4150; IR (CCl4): nmax 2930 (m), 2930 (m) cm–1. Anal. Calcd for C60H76N4RhI·CH3OH: C 65.70, H 7.23, N 5.02. Found: C 65.23, H 7.19, N 5.02.
118 · NH3 complex (119)
Method 1
The compound was prepared unintentionally by the use of Fluorochem silica during the purification of 118. A mixture of 118 and 119 was obtained which could be converted to solely 119 by warming with a slurry of Fluorochem silica in CHCl3. After filtration and evaporation of the solvent pure 5 was obtained as an orange solid.
Method 2
A solution of 118 (5 mg, 4.6 mmol) in DCM (1 mL) was treated with vapour from aqueous NH3 solution for 30 min at rt. The solvent was evaporated by blowing with N2, and the product obtained quantitatively after drying in vacuo.
Crystals for structure determination were obtained from a toluene solution layered with MeOH.
1H NMR (400 MHz, CDCl3): d 10.23 (s, 2H, meso), 8.14 (d, J = 7 Hz, 2H, Ar), 7.98 (d, J = 7 Hz, 2H, Ar), 7.78 - 7.68 (m, 6H, Ar), 4.00 (m, 4H, hex H1), 3.89 (m, 4H, hex H1), 2.45 (s, 12H, CH3), 2.22 (m, 8H, hex H2), 1.80 (m, 8H, hex H3), 1.55 (m, 8H, hex H4), 1.43 (m, 8H, hex H5), 0.95 (t, J = 7 Hz, 12H, hex H6), -5.77 (s, 3H, NH3); 13C NMR (100.6 MHz, CDCl3): d 144.1, 142.8, 140.5, 140.1, 138.6, 134.0, 132.8, 128.3, 127.8, 127.2, 119.3, 98.8, 33.4, 32.0, 30.3, 27.1, 22.8, 15.6, 14.2; UV/vis (DCM): lmax 360, 420, 532, 562 nm; MALDI MS: m/z [M - NH3]+ 1084; IR (CCl4): nmax 3381 (w), 2957 (s), 2930 (s), 2858 (m) cm–1; Anal. Calcd for C60H79IN5Rh: C 65.51, H 7.24, N 6.37. Found: C 65.70, H 7.43, N 6.03.
Rh meso oxoporphyrin (120)
120 was isolated in small (~1 mg) quantities during chromatography of 119 prepared inadvertently by method 1. 120 is visible as a fast moving bright yellow band on the column. Crystals for structure determination were obtained from a CDCl3 solution layered with MeOH.
1H NMR (400 MHz, CDCl3): d 7.35 (m, 6H, Ar), 7.15 (m, 2H, Ar), 5.02 (s, 1H, meso), 1.82 (m, 4H), 1.74 (m, 4H), 1.42 (s), 1.43 (s), 1.26 - 1.13 (br m), 0.89 - 0.80 (m), 0.68 (s, 6H), 0.49 (s, 6H); 13C NMR (100.6 MHz, CDCl3): d 154.2, 150.2, 146.9, 146.6, 146.2, 144.7, 140.4, 136.2, 135.1, 129.2, 128.2, 31.5, 31.4, 30.6, 29.7, 29.4, 29.2, 29.0, 24.0, 23.9, 22.5, 14.1, 14.0, 13.2, 12.1; UV/vis (DCM): lmax262, 280, 400, 484 nm; MALDI MS: m/z [M - 2I]+ 972.5.
(118)2 · 4,4'-Bipyridine complex (121)
To a stirred solution of 4,4'-bipyridine (50 mg, 0.32 mmol) in THF (0.5 mL) was added 118 (40 mg, 0.037 mmol) in THF (1 mL). After stirring for 3 h at room temperature, the solvent was evaporated and the residue chromatographed on silica eluted with DCM/hexane (1/1) to afford the product as an orange solid (32 mg, 75 %). Rf 0.33 (hexane/DCM, 1/1).
Crystals for structure determination were obtained from a mixed DCM/CHCl3 solution layered with MeOH.
1H NMR (400 MHz, CDCl3): d 9.97 (s, 4H, meso), 7.92 (d, J = 8 Hz, 4H, Ar), 7.70 (m, 8H, Ar), 7.60 (m, 8H, Ar), 4.11 (d, J = 7 Hz, 4H, bpy Hb), 3.76 (m, 16H, hex H1), 2.30 (s, 24H, CH3), 1.99 (m, 16H, hex H2), 1.59 (m, 16H, hex H3), 1.37 (m, 16H, hex H4), 1.25 (m, 16H, hex H5), 0.79 (t, J = 7 Hz, 24 H, hex H6), 0.39 (d, J = 7 Hz, 4H, bpy Ha); 13C NMR (100.6 MHz, CDCl3): d 144.6, 143.9, 142.6, 140.4, 139.6, 138.4, 133.8, 132.7, 128.2, 127.7, 127.0, 119.1, 117.5, 98.6, 33.2, 31.9, 30.0, 26.9, 22.7, 15.4, 14.1; UV/vis (DCM): lmax 358, 420, 532, 560 nm; Anal. Calcd for C130H160N10Rh2I2 C 67.23, H 6.94, N 6.03. Found: C 67.12, H 6.89, N 5.92.
5,15-Bis(4-methoxycarbonyl-phenyl)-2,8,12,18-tetrahexyl-3,7,13,17-tetramethyl porphyrinato rhodium(III) iodide (122)
5,15-Bis(4-methoxycarbonyl-phenyl)-2,8,12,18-tetrahexyl-3,7,13,17-tetramethyl porphyrin, obtained as a symmetrical side product from the preparation of unsymmetrical porphyrins, was metallated using an analogous procedure to the synthesis of 118. The product was obtained as an orange solid (144 mg, 58 %) after chromatography on Merck silica eluted with DCM. A sample for analysis was recrystallized from DCM layered with MeOH. Rf 0.46 (DCM).
1H NMR (400 MHz, CDCl3): d 10.30 (s, 2H, meso), 8.46 (m, 2H, Ar), 8.39 (m, 2H, Ar), 8.28 (m, 2H, Ar), 8.05 (m, 2H, Ar), 4.13 (s, 6H, OCH3), 4.02 (m, 4H, hex H1), 3.87 (m, 4H, hex H1), 2.46 (s, 12H, CH3), 2.15 (m, 8H, hex H2), 1.74 (m, 8H, hex H3), 1.48 (m, 8H, hex H4), 1.39 (m, 8H, hex H5), 0.91 (t, J = 7 Hz, 12H, hex H6); 13C NMR (100.6 MHz, CDCl3): d 167.3, 147.5, 144.8, 141.2, 140.7, 138. 4, 133.5, 133.2, 130.2, 128.8, 128.6, 119.5, 100.5, 52.4, 33.1, 31.9, 30.0, 26.9, 22.7, 15.9, 14.1; UV/vis (DCM): lmax 404, 522, 550 nm; MALDI MS: m/z [M-I]+ 1072; IR (CCl4): nmax 1728 (s) cm–1; Anal. Calcd for C64H80O4N4RhI ·CH3OH: C 63.41, H 6.88, N 4.55. Found: C 62.99, H 6.87, N 4.38.
2,8,12,18-Tetrahexyl-3,7,13,17-tetramethyl-5,15-diphenyl-porphyrinato rhodium(III) methyl (123)
To a degassed solution of 121 (10 mg, 4.3 mmol) in dry THF (2 mL) was added MeLi (0.5 mL, 1.6 M in Et2O). After stirring for several seconds EA (0.5 mL) was added. The solvent was evaporated and the residues chromatographed on silica gel eluted with hexane/DCM (4/1). The product was obtained as an air stable orange solid (7.1 mg, 85 %). Rf 0.44 (hexane/DCM, 4/1).
Crystals for structure determination were obtained from a DCM solution layered with MeOH.
1H NMR (250 MHz, CDCl3): d 10.04 (s, 2H, meso), 8.08 (d, J = 7 Hz, 2H, Ar), 7.97 (d, J = 6 Hz, 2H, Ar), 7.73 (m, 6H, Ar), 3.86 (m, 8H, hex H1), 2.38 (s, 12H, CH3), 2.15 (m, 8H, hex H2), 1.72 (m, 8H, hex H3), 1.51 - 1.29 (m, 16H, hex H4,5), 0.90 (t, J = 7 Hz, 12H, hex H1), -6.06 (d, J = 3 Hz, 3H, CH3); 13C NMR (100.6 MHz, CDCl3): d 143.0, 142.9, 140.6, 140.2, 137.3, 2 ´ 133.3, 128.1, 127.4, 120.2, 99.4, 33.1, 32.0, 30.0, 26.7, 22.7, 15.3, 14.1; UV/vis (DCM): lmax 402, 516, 548 nm; FIB MS: m/z [M]+ 973.7; IR (CCl4): nmax 2958 (s), 2930 (s), 2859 (s), 1467 (m), 1445 (m) cm–1.
118 · Pyridine complex (124)
To a stirred solution of 118 (20 mg, 0.018 mmol) in CHCl3 (1 mL) was added pyridine (50 ml). After several minutes the solvent and excess pyridine were removed under reduced pressure to afford the product as an orange solid in quantitative yield.
Crystals for structure determination were obtained from a toluene solution layered with MeOH.
1H NMR (400 MHz, CDCl3): d 10.18 (s, 2H, meso), 8.03 (t, J = 8 Hz, 4H, Ar), 7.78 (m, 2H, Ar), 7.70 (m, 4H, Ar), 5.93 (tt, J = 7, 1 Hz, 1H, pyr Hg), 4.98 (t, J = 7 Hz, 2H, pyr Hb), 3.92 (m, 8H, hex H1), 2.45 (s, 12H, CH3), 2.17 (m, 8H, hex H2), 1.71 (m, 8H, hex H3), 1.48 (m, 8H hex H4), 1.37 (m, 8H, hex H5), 0.89 (t, J = 7 Hz, 12H, hex H6), 0.81 (d, J = 6 Hz, 2H, pyr Ha); 13C NMR (100.6 MHz, CDCl3): d 144.5, 144.0, 143.0, 140.1, 139.8, 138.4, 134.3, 133.9, 133.1, 128.2, 127.7, 127.1, 121.2, 119.2, 98.8, 33.2, 32.0, 30.1, 27.0, 22.8, 15.6, 14.1; UV/vis (DCM): lmax 358, 422, 532, 560 nm; Anal. Calcd for C65H81N5RhI: C 67.18, H 7.02, N 6.03. Found: C 66.56, H 6.91, N 5.57.
4,4'-Bipyrimidine (125)262
A solution of BuLi (2 mL, 1.6 M in hexane) was added dropwise to a solution of 2,2,6,6-tetramethylpiperidine (0.55 mL, 3.24 mmol) in THF (20 mL) at -30 °C. After stirring at 0 °C for 30 min, followed by cooling to -79 °C, to this was added dropwise pyrimidine (220 mL, 2.79 mmol) in THF (5 mL). Stirring was continued at -79 °C for 1 h, after which HCl (5 mL, saturated in THF/EtOH, 1/1) was added dropwise to form a brown precipitate. After warming to rt, satd. NaHCO (25 mL) was added to dissolve the solids. The solution was extracted with DCM (3 ´ 50 mL) and the combined organic extracts dried (MgSO4) and evaporated to a cream solid. Column chromatography on silica eluted with EA/DCM (3/2) afforded the product as a white solid (109 mg, 49 %). Rf 0.33 (EA/DCM, 3/2).
1H NMR (250 MHz, CDCl3): d 9.35 (d, J = 1 Hz, 2H, H3), 8.96 (d, J = 5 Hz, 2H, H6), 8.43 (dd, J = 5, 1 Hz, 2H, H5); Anal. Calcd for C8H6N4: C 60.75, H 3.82, N 35.42. Found: C 60.17, H 3.70, N 34.78.
(118)2 · 4,4'-Bipyrimidine (126)
This was prepared in an identical manner to 121, using 125 instead of 4,4'-bipyridine. Purified by column chromatography on silica eluting with hexane/DCM (4/3 gradient to 1/1). Orange solid (33 mg, 77 %). Rf 0.47 (hexane/DCM, 1/1).
Crystals for structure determination were obtained from CHCl3/DCM solution layered with MeOH.
1H NMR (400 MHz, CDCl3): d 9.99 (s, 4H, meso), 7.90 (d, J = 7 Hz, 4H, Ar), 7.74 (m, 8H, Ar), 7.61 (m, 8H, Ar), 4.98 (dd, 2H, J = 6, 1 Hz, bpm H6), 3.82 (m, 8H, hex H1), 3.71 (m, 8H, hex H1), 2.31 (s, 24H, CH3), 2.00 (m, 16H, hex H2), 1.57 (m, 16H, hex H3), 1.37 (m, 16H, hex H4), 1.25 (m, 16H, hex H5), 1.07 (s, 2H, bpm H3), 0.79 (t, J = 7 Hz, 24H, hex H6), 0.67 (d, J = 6 Hz, 2H, bpm H5); 13C NMR (100.6 MHz, CDCl3): d 155.2, 152.7, 144.1, 142.4, 139.9, 139.6, 138.6, 133.8, 132.8, 128.3, 127.8, 127.1, 119.2, 113.9, 33.1, 31.9, 30.0, 26.9, 22.7, 15.4, 14.0; UV/vis (DCM): lmax 358, 418, 530, 560 nm; Anal. Calcd for C128H158N12Rh2I2: C 66.14, H 6.85, N 7.23. Found: C 65.94, H 6.80, N 7.08.
4,4'-Bipyrimidine rhenium tricarbonyl chloride (127)266
Re(CO)5Cl (181 mg, 0.50 mmol) and 125 (79 mg, 0.50 mmol) were refluxed in degassed toluene (25 mL) under N2 for 2 h. After cooling to room temperature the brown precipitate was collected and washed with Et2O (10 mL). The Et2O washings were discarded and the residues washed with CHCl3 (100 mL). Hexane was added to the filtrate to precipitate the product as an orange solid (51 mg, 22 %).
1H NMR (250 MHz, DMSO-d6): 9.79 (d, 2H, J = 1 Hz, H2), 9.44 (d, J = 5 Hz, 2H, H6), 8.99 (dd, J = 5, 1 Hz, 2H, H5); 13C NMR (62.9 MHz, DMSO-d6): 196.6, 161.5, 161.0, 160.7, 121.0; FAB MS: m/z [M]+ 464.1; Anal. Calcd for C11H6O3N4ReCl: C 28.48, H 1.30, N 12.08. Found: C 28.74, H 1.35, N 11.63.
4,4'-Bipyrimidine molybdenum tetracarbonyl (128)265
Mo(CO)6 (0.33 g, 1.2 mmol) and 125 (50 mg, 0.32 mmol) were refluxed in degassed THF (5 mL) under Ar for 24 h. The solution turned from yellow to green then deep blue over several minutes. After filtration through celite the solvent was evaporated to afford a dark purple solid which was recrystallized from CHCl3/hexane then chromatographed on a short silica column eluted with hexane/DCM (7/3) to afford the product as a black solid (32 mg, 28 %). Rf 0.31 (DCM/EA, 7/3).
1H NMR (250 MHz, Acetone-d6): 9.76 (d, J = 1 Hz, 2H, H2), 9.22 (d, J = 5 Hz, 2H, H6), 8.77 (dd, J = 5, 1 Hz, 2H, H5); Anal. Calcd for C12H6O4N4Mo: C 39.36, H 1.65, N 15.30. Found: C 39.56, H 1.77, N 15.10.
N,N'-Dimethyl-1,4,5,8-naphthalenetetracarboxylic diimide (129)268
Methylamine (100 mL, 40 % aq) was added to naphthalene tetracarboxylic acid hydrate (31.0 g, 0.10 mol). The solution was warmed to boiling and sonicated briefly, then evaporated under reduced pressure to afford a brown solid. To this was added N-methyl pyrrolidinone (500 mL) and heated to 150 °C for 2 h. After cooling to 80 °C the solution was filtered to collect the product which was washed with MeOH until the washings were colourless. After drying the product was used without further purification. Pink needles (16.1 g, 54 %).
Anal. Calcd for C16H10N2O4: C 65.31, H 3.43, N 9.52. Found: C 64.94, H 3.46, N 9.65.
1,3,6,8-Tetrahydro-2,7-dimethyl-2,7-diazapyrene (130)271
LiAlH4 (14.7 g, 0.39 mol) was added to a solution of AlCl3 (17.2 g, 0.13 mol) in THF (300 mL) at 0 °C. To this was added 129 (16.1 g, 55 mmol) in portions over several minutes. The green solution was stirred at rt for 30 min, then refluxed for 4 h. After cooling the solution was poured into a mixture of THF (500 mL) and ice (100 mL). The resulting slurry was filtered, and the brown filtrate concentrated to 50 mL to produce a brown precipitate of 130 which was collected. The residues were washed with THF (3 ´ 100 mL) and after concentration, further 130 precipitated. The residues were further extracted with boiling CHCl3 (4 ´ 500 mL). After evaporation of the solvent a further portion of 130 was obtained as a yellow solid (combined mass 8.89 g, 68 %).
1H NMR (400 MHz, CDCl3): 7.12 (s, 4H, Ar), 3.88 (s, 8H, CH2N), 2.57 (s, 6H, CH3).
2,7-Diazapyrene (131)269
Pd/C (2.0 g, 10 % Pd) and 130 (2.0 g, 8.4 mmol) were ground together and packed into a Schlenk tube which was evacuated then placed under N2. The tube was heated to ~300 °C for 1 h, with periodic exposure to vacuum. After cooling to rt, HCl (20 mL, 3 N) was added and the solids removed by filtration through celite. The green filtrate was basified by addition of NaOH (10 %) to produce a brown precipitate, which was filtered, washed with water and dried in vacuo. The product was purified by passage through a column of basic alumina (toluene/DCM 1/1, 3 % Et3N), followed by sublimation (140 °C, 0.05 mmHg), then chromatography on silica (CHCl3/MeOH, 20/1). Pale yellow solid (32 mg, 2 %). Rf 0.33 (CHCl3/MeOH, 20/1).
1H NMR (400 MHz, CDCl3): d 9.51 (s, 4H, H2), 9.21 (s, 4H, H3).
(118)2 · Diazapyrene complex (132)
118 (21 mg, 19 mmol) and 131 (2.0 mg, 9.8 mmol) were mixed and CDCl3 (1.0 mL) added (to allow for acquisition of the NMR spectrum of the reaction mixture). After stirring for 3 h the solvent was evaporated and the residue purified by chromatography on silica gel (hexane/DCM,1/1 gradient to DCM) to afford an orange solid (10 mg, 44 %). Rf 0.30 (hexane/DCM, 1/1).
Crystals for structure determination were grown from a CHCl3 solution layered with hexane.
1H NMR (400 MHz, CDCl3): d 10.04 (s, 4H, meso), 7.98 (d, J = 7 Hz, 4H, Ar), 7.65 (m, 12H, Ar), 7.52 (m, 4H, Ar), 5.64 (s, 4H, dap H3), 3.86 (m, 8H, hex H1), 3.71 (m, 8H, hex H1), 2.30 (s, 24H, CH3), 2.01 (m, 16H, hex H2), 1.57 (m, 16H, hex H3), 1.33 (m, 16H, hex H4), 1.21 (m, 16H, hex H5), 1.08 (s, 4H, dap H2), 0.76 (t, J = 7 Hz, 24H, hex H6); 13C NMR (100.6 MHz, CDCl3): d 143.9, 142.6, 2 ´ 140.0, 139.7, 138.4, 133.8, 132.6, 128.2, 127.7, 127.0, 124.2, 122.0, 121.6, 119.2, 98.7, 33.1, 31.8, 29.9, 26.8, 22.6, 15.4, 14.0; UV/vis (DCM): lmax 342, 420, 532, 560 nm; Anal. Calcd for C134H160N10Rh2I2: C 67.90, H 6.80, N 5.91. Found: C 67.98, H 6.28, N 5.50.
5,5'-Dimethyl-2,2'-bipyridine (133)274,275
NiAl alloy (71 g) was added portionwise over several minutes to a stirred solution of NaOH (90.7 g, 2.3 mol) in ice cold water (340 mL) (cautionfoaming). After the addition was complete the suspension was heated on a steam bath for 30 min. An additional portion of water (340 mL) was added and the supernatant liquid decanted off. The grey solids were washed with water (5 ´ 300 mL) then dried in vacuo by heating with a steam bath for 90 min. After cooling to rt, the activated Ni catalyst was placed under N2. 3-Picoline (90 mL, 0.92 mol) was added dropwise to the catalyst ensuring air did not enter the apparatus until the addition was complete. The picoline was refluxed over the catalyst under dry air for 48 h, after which the catalyst was removed by filtration and rinsed with toluene (100 mL). The filtrate was evaporated to a brown solid which was extracted with boiling 60/80 petroleum ether (250 mL). The extracts were filtered hot, then a further portion of 60/80 petroleum ether (750 mL) added. After swirling with activated charcoal for 5 min, and filtration through celite, the solution was evaporated to yellow solids which were recrystallized from boiling EtOH to afford the product as pale yellow crystals (18.1 g, 21 %).
1H NMR (250 MHz, CDCl3): d 8.47 (d, J = 2 Hz, 2H, H6), 8.22 (d, J = 8 Hz, 2H, H3), 7.59 (dd, J = 8, 2 Hz, 2H, H4), 2.36 (s, 6H, CH3); Anal. Calcd for C12H12N2: C 78.23, H 6.56, N 15.21. Found: C 78.15, H 6.56, N 15.23.
5,5'-Dicarboxy-2,2'-bipyridine (134)276
133 (10.54 g, 57 mmol) was added portionwise to stirred conc. H2SO4 (125 mL) maintaining the temperature in the range 5 - 10 °C. To the cooled solution (ice bath) was added finely divided CrO3 (32.8 g, 0.33 mol) portionwise over 90 min. The solution was allowed to warm to rt over 150 min, after which conc. H2SO4 (50 mL) was added followed by heating to 56 °C for 18 h. Water (300 mL) was added (caution exothermic) and the resulting slurry poured into iced water (700 mL). After allowing the solids to settle, the green supernatant was decanted and celite (20 g) and water (500 mL) added to the remaining suspension. The solids were filtered onto a pad of celite, which was washed with water (200 mL). The celite was resuspended in water (1 L) and the pH adjusted to 8.5 using NaOH (10 % aq) and HCl (3 N). After filtration the yellow filtrate was acidified to pH 2 with HCl (3 N) to form a white precipitate which was collected and washed with water (50 mL), acetone (50 mL) and Et2O (50 mL). After drying overnight in an oven (70 °C) the product was obtained as a white powder (12.2 g, 87 %) and used without further purification.
5,5'-Dicarboxyethyl-2,2'-bipyridine (135)277
134 (4.0 g, 16 mmol) was refluxed in EtOH (200 mL) and conc. H2SO4 (70 mL) for 21 h. After cooling to room temperature the solution was poured into water (1 L) to form a white precipitate. The pH was adjusted to 8 by addition of conc. NH3 and the precipitates collected by filtration and washed with water. After drying in vacuo and recrystallization from EtOH the product was obtained as almost colourless needles (2.66 g, 54 %).
1H NMR (400 MHz, CDCl3): d 9.29 (dd, J = 2, 1 Hz, 2H, H6), 8.57 (dd, J = 8, 1 Hz, 2H, H3), 8.43 (dd, J = 8, 2 Hz, 2H, H4), 4.15 (q, J = 7 Hz, 4H, CH2O), 1.44 (t, J = 7 Hz, 6H, CH3); Anal. Calcd for C16H16N2O4: C 63.99, H 5.37, N 9.33. Found: C 63.65, H 5.32, N 9.29.
5,5'-Dicarboxamide-2,2'-bipyridine (136)273
A solution of 135 (2.66 g, 8.86 mmol) in EtOH (90 mL) and ethylene glycol (90 mL) was saturated with NH3 and stirred at 95 °C under an NH3 atmosphere for 2 d. The gelatinous white precipitate was collected by filtration and washed with ethylene glycol (20 mL) and hot EtOH (20 mL). The filtrate was retained. The solids were resuspended in EtOH (30 mL), filtered and dried in an oven. As 1H NMR indicated the presence of starting material the solids were recombined with the filtrate from the initial filtration. An additional portion of EtOH (40 mL) was added, the mixture was saturated with NH3 and refluxed for 1 d under NH3. After cooling to rt the precipitate was filtered, washed with EtOH and dried in an oven (80 °C) to obtain the product as a white powder (1.16 g, 54 %) which was used without purification.
5,5'-Dicyano-2,2'-bipyridine (137)278
A mixture of 136 (0.20 g, 0.83 mmol) and P4O10 (0.5 g) was heated in a sublimator under vacuum. The white hygroscopic solids that sublimed were mixed with P4O10 (0.5 g) and sublimed again to obtain a small quantity (17 mg) of product which was further purified by passage through a short silica plug eluted with CHCl3 to afford the product as a white solid (8 mg, 5 %).
1H NMR (400 MHz, CDCl3): d 8.96 (dd, J = 2, 1 Hz, 2H, H6), 8.63 (dd, J = 8, 1 Hz, 2H, H3), 8.14 (dd, J = 8, 2 Hz, 2H, H4); 13C NMR (100.6 MHz, CDCl3): d 156.9, 152.1, 140.5, 121.6, 116.5, 110.7.
(118)2 · DABCO (139)
Prepared by titration of a solution of 118 (3.95 mg, 3.5 mmol) in CDCl3 (600 mL) with DABCO in CDCl3. After titration the sample was loaded onto a silica column and eluted with hexane/DCM (1/1). The porphyrin containing eluent was evaporated, redissolved in DCM and layered with MeOH to obtain crystals of 139 for structure determination.
1H NMR (400 MHz, CDCl3): d 9.70 (s, 4H, meso), 7.75 (m, 8H, Ar), 7.66 (t, J = 7 Hz, 4H, Ar), 7.59 (t, J = 7 Hz, 4H, Ar), 7.37 (d, J = 7 Hz, 4H, Ar), 3.67 (m, 16H, hex H1), 2.21 (s, 24H, CH3), 1.82 (m, 16H, hex H2), 1.57 (m, 16H, hex H3), 1.43 (m, 32H, hex H4,5), 0.93 (t, J = 7 Hz, 24H, hex H6), -6.05 (s, 12H, NCH2).
Isonicotinic acid undecyl ester (140)
Isonicotinic acid (0.50 g, 4.1 mmol), SOCl2 (280 mL) and pyridine (0.67 g) were heated to 100 °C under N2 for 1 h. 1-Undecanol (0.75 mL, 3.6 mmol) was added and the mixture stirred at 100 °C for a further 3 h after which water (10 mL) was added and the mixture basified by addition of NaOH (10 % aq). The red solution was extracted with Et2O (3 ´ 30 mL), dried (MgSO4) and evaporated to a red oil. The product was precipitated as a salt from Et2O solution by addition of conc. H2SO4. The yellow solids were filtered and washed with Et2O, placed in a separating funnel and shaken with a mixture of CHCl3 (30 mL), water (10 mL) and satd. Na2CO3 (10 mL) until all the solids had dissolved. The organic phase was dried (MgSO4) and evaporated to a red oil which was eluted through a silica gel plug with hexane/EA (3/1) to afford the product as a colourless oil after removal of the solvent. (0.69 g, 69 %). Rf 0.40 (hexane/EA, 3/1).
1H NMR (250 MHz, CDCl3): d 8.72 (d, J = 5.0 Hz, 2H, pyr H2,6), 7.78 (dd, J = 5, 2 Hz, 2H, pyr H3,5), 4.29 (t, J = 7 Hz, 2H, OCH2), 1.72 (m, 2H, CH2), 1.60 - 1.21 (m, 16H, (CH2)8), 0.82 (t, J = 7 Hz, 3H, CH3); 13C NMR (62.9 MHz, CDCl3): d 165.1, 150.6, 137.6, 122.8, 65.9, 31.9, 2 ´ 29.5, 29.3, 29.2, 28.5, 25.9, 22.6, 14.1; FAB MS: m/z [M+H]+ calcd 278.2120, found 278.2125; IR (CCl4): nmax 2956 (m), 2927 (s), 2855 (m), 1732 (s), 1279 (s) cm–1; Anal. Calcd for C17H27O2N: C 73.61, H 9.81, N 5.05. Found: C 73.96, H 9.80, N 5.06.
2,8,12,18-Tetrahexyl-3,7,13,17-tetramethyl-5,15-diphenyl-porphyrinato tin(IV) dichloride (142)
SnCl2 (0.10 g, 0.53 mmol) and 117 (80 mg, 94 mmol) were refluxed in pyridine (5 mL) under air for 7 h. and allowed to cool to rt. Water (20 mL) was added and the red precipitate filtered onto celite and washed with MeOH (50 mL). The porphyrin was extracted from the celite with CHCl3 (70 mL), and the organic solution washed with HCl (3 N, 2 ´ 20 mL) and water (2 ´ 20 mL), dried (Na2SO4) and evaporated to a red solid which was used without further purification (95 mg, 97 %).
1H NMR (400 MHz, CDCl3): d 10.60 (s, 2H, meso), 8.16 (m, 4H, Ar), 7.86 (m, 2H, Ar), 7.80 (m, 4H, Ar), 4.06 (t, J = 8 Hz, 8H, hex H1), 2.57 (s, 12H, CH3), 2.30 (m, 8H, hex H2), 1.85 (m, 8H, hex H3), 1.58 (m, 8H, hex H4), 1.44 (m, 8H, hex H5), 0.97 (t, J = 7 Hz, 12H, hex H6); 13C NMR (100.6 MHz, CDCl3): d 144.4, 143.8, 142.8, 141.5, 139.6, 133.3, 129.1, 128.0, 119.4, 96.9, 33.1, 31.9, 30.2, 27.0, 22.7, 15.2, 14.1; UV/vis (DCM): lmax 418, 548, 582 nm; Anal. Calcd for C60H76N4SnCl2: C 69.10, H 7.35, N 5.37. Found C 69.09, H 7.36, N 5.20.
2,8,12,18-Tetrahexyl-3,7,13,17-tetramethyl-5,15-diphenyl-porphyrinato tin(IV) dihydroxide (143)
Activity I basic alumina (10 g) was shaken with water (2 mL) until homogenous. To this was added 142 (91 mg, 73 mmol) in CHCl3 (10 mL). Light was excluded and the suspension stirred for 1 d at rt. The suspension was filtered through celite which was washed with CHCl3 (100 mL) to remove all porphyrin. The filtrate was evaporated to afford the product as a purple solid which was used without further purification (89 mg, 100 %).
1H NMR (500 MHz, CDCl3): d 10.51 (s, 2H, meso), 8.17 (m, 4H, Ar), 7.85 (m, 2H, Ar), 7.78 (t, J = 7 Hz, 4H, Ar), 4.03 (t, J = 8 Hz, 8H, hex H1), 2.52 (s, 12H, CH3), 2.28 (m, 8H, hex H2), 1.83 (m, 8H, hex H3), 1.55 (m, 8H, hex H4), 1.44 (m, 8H, hex H5), 0.96 (t, J = 7 Hz, 12H, hex H6), -7.84 (s, 2H, OH); 13C NMR (100.6 MHz, CDCl3): d 2 ´ 144.2, 143.1, 142.3, 139.3, 133.3, 128.8, 127.9, 119.4, 97.2, 33.2, 31.9, 30.1, 29.7, 26.9, 22.8, 15.1, 14.2; UV/vis (DCM): lmax 416, 548 nm; MALDI MS: m/z [M-OH]+ 989; IR (CCl4): nmax 3644 (w), 2958 (s), 2930 (s), 2858 (s) cm–1; Anal. Calcd for C60H78N4SnO2: C 71.64, H 7.81, N 5.57. Found: C 71.18, H 7.90, N 5.39.
5-(4-Methoxycarbonyl-phenyl)-15-(4-pyridyl)-2,8,12,18-tetrahexyl-3,7,13,17-tetramethyl porphyrin (147)
Prepared using the standard porphyrin synthesis procedure from 4-formyl-pyridine and 4-formyl-methyl-benzoate. After purification by column chromatography on silica eluted with DCM/EA (10/1) the product was obtained as a dark purple solid (67 mg, 7 %). Rf 0.52 (DCM/EA, 10/1).
1H NMR (500 MHz, CDCl3): d 10.26 (s, 2H, meso), 9.02 (d, J = 5 Hz, 2H, pyr Ha), 8.44 (d, J = 8 Hz, 2H, Ar), 8.18 (d, J = 8 Hz, 2H, Ar), 8.06 (d, J = 5 Hz, 2H, pyr Hb), 4.14 (s, 3H, OCH3), 3.97 (m, 8H, hex H1), 2.51 (s, 6H, CH3), 2.46 (s, 6H, CH3), 2.18 (m, 8H, hex H2), 1.73 (m, 8H, hex H3), 1.47 (m, 8H, hex H4), 1.37 (m, 8H, hex H5), 0.90 (t, J = 7 Hz, 12H, hex H6), -2.39 (br s, 2H, NH); 13C NMR (100.6 MHz, CDCl3): d 167.3, 150.8, 149.0, 147.3, 144.7, 2 ´ 144.0, 143.8, 141.7, 141.5, 136.0, 135.3, 133.1, 130.2, 128.8, 128.5, 117.0, 114.5, 97.4, 52.4, 2 ´ 33.3, 32.0, 2 ´ 30.0, 26.8, 22.7, 15.0, 14.8, 14.1; UV/vis (DCM): lmax 408, 506, 574, 626 nm; ES MS: m/z [M+H]+ calcd 914.6312, found 914.6320; IR (CCl4): nmax 2956 (s), 2930 (s) 2858 (m), 1728 (s) cm–1.
5-(4-Carboxy-phenyl)-15-(4-pyridyl)-2,8,12,18-tetrahexyl-3,7,13,17-tetramethyl porphyrin (148)
A solution of 147 (40 mg, 44 mmol) and KOH (100 mg, 1.8 mmol) in a mixture of THF (13.5 mL) and water (125 mL) was heated to 40 °C for 1 d. Tlc indicated the presence of starting material. KOH (38 mg) and water (100 mL) were added and stirring was continued at the same temperature overnight. Addition of a further portion of water (100 mL) and heating at reflux for 1 h was required to complete the reaction. After cooling to rt, HCl (3 N, 50 mL) was added and the solution extracted with CHCl3 (2 ´ 50 mL). The green organic layer was washed with water (3 ´ 100 mL), dried (MgSO4) and evaporated to a brown solid. Column chromatography on silica eluted with DCM/EA (10/1) gradient to DCM/MeOH (10/1) afforded the product as a purple solid (27 mg, 69 %).
1H NMR (500 MHz, CD3OD + CDCl3): d 10.21 (s, 2H, meso), 8.90 (br d, 2H, pyr Ha), 8.40 (d, 2H, J = 8 Hz, Ar), 8.11 (d, 2H, J = 8 Hz, Ar), 8.07 (d, J =5 Hz, 2H, pyr Hb), 3.91 (br, 8H, hex H1), 2.44 (s, 6H, CH3), 2.40 (s, 6H, CH3), 2.12 (m, 8H, hex H2), 1.67 (m, 8H, hex H3), 1.41 (m, 8H, hex H4), 1.31 (m, 8H, hex H5), 0.84 (t, J = 7 Hz, 12H, hex H6); 13C NMR (100.6 MHz, CD3OD + CDCl3): d 168.9, 151.5, 148.4, 147.0, 144.6, 144.1, 143.8, 143.7, 141.7, 141.4, 136.1, 135.1, 133.0, 130.5, 129.1, 128.8, 117.3, 114.0, 97.4, 2 ´ 33.2, 31.9, 29.9, 26.7, 22.6, 14.9, 14.7, 14.0; UV/vis (DCM): lmax 408, 506, 540, 574 nm; ES MS: m/z [M+H]+ calcd 900.6156, found 900.6166.
4-Trimethylsilylethynyl-benzaldehyde (152)466
A mixture of 4-bromobenzaldehyde (5.0 g, 27 mmol), Pd(OAc)2 (0.36 g, 1.6 mmol), PPh3 (0.56 g, 2.1 mmol), trimethylsilylacetylene (5.8 mL, 41 mmol) and Et3N (dry, 50 mL) was degassed and refluxed under Ar for 6 h. After cooling overnight the black solution was poured into water (300 mL) and extracted with DCM (4 ´ 100 mL). The combined organic extracts were dried (MgSO4), and evaporated to a brown oil. Column chromatography on silica gel eluting with hexane/EA (10/1) followed by recrystallization from cold (-79 °C) hexane afforded the product as pale yellow crystals (3.12 g, 57 %). Rf 0.43 (hexane/EA, 10/1).
1H NMR (250 MHz, CDCl3): d 9.99 (s, 1H, CHO), 7.81 (d, J = 8 Hz, 2H, Ar), 7.59 (d, J = 8 Hz, 2H, Ar), 0.26 (s, 9H, SiCH3); Anal. Calcd for C12H14OSi: C 71.24, H 6.97. Found: C 71.24, H 6.99.
3,5-Diiodobenzaldehyde (153)467
To a solution of 3,5-diiodobenzyl alcohol (2.7 g, 7.5 mmol) in THF (10 mL) and DCM (5 mL) was added PCC (3.0 g, 13.9 mmol) suspended in DCM (10 mL). The solution was stirred for 2 h at rt, after which Et2O (75 mL) was added. The brown precipitate was removed by filtration through celite, which was washed with a portion of Et2O (50 mL). The combined filtrates were evaporated to a yellow solid, which was redissolved in hexane/EA mixture and evaporated onto silica gel. The silica was loaded onto a short column and eluted with hexane/EA (20/1) to afford the product as yellow crystals. (2.1 g, 78 %).
1H NMR (500 MHz, CDCl3): d 9.83 (s, 1H, CHO), 8.29 (s, 1H, H4), 8.14 (s, 2H, H2,6).
5-(4-Trimethylsilylethynyl-phenyl)-15-(4-pyridyl)-2,8,12,18-tetrahexyl-3,7,13,17-tetramethyl porphyrin (154)
Synthesized according to the standard procedure, and isolated by chromatography on silica, eluted with DCM/EA (15/1 gradient to 10/1). Further purification was carried out using a second column eluted with DCM/EA (15/1) and recrystallization from CHCl3 layered with MeOH. Deep red crystals (0.31 g, 13 %). Rf 0.35 (DCM/EA, 15/1).
1H NMR (400 MHz, CDCl3): d 10.25 (s, 2H, meso), 9.02 (d, J = 6 Hz, 2H, pyr Ha), 8.07 (d, J = 6 Hz, 2H, pyr Hb), 8.02 (d, J = 8 Hz, 2H, Ar), 7.87 (d, J = 8 Hz, 2H, Ar), 3.97 (m, 8H, hex H1), 2.51 (s, 6H, CH3), 2.50 (s, 6H, CH3), 2.18 (m, 8H, hex H2), 1.73 (m, 8H, hex H3), 1.48 (m, 8H, hex H4), 1.37 (m, 8H, hex H5), 0.90 (t, J = 7 Hz, 12 H, hex H6), -2.42 (s, 2H, NH).
5-(4-Ethynyl-phenyl)-15-(4-pyridyl)-2,8,12,18-tetrahexyl-3,7,13,17-tetramethyl porphyrin (155)468
To a solution of 154 (250 mg, 0.26 mmol) in THF (10 mL) and water (100 mL) was added TBAF (1 M in THF, 290 mL, 0.29 mmol). After stirring for 50 min at rt a precipitate had formed. After this time water (50 mL) was added and the suspension extracted with CHCl3 (2 ´ 50 mL). The combined organic phase was washed with water and dried (MgSO4). The solvent was evaporated and the resulting solids recrystallized from CHCl3 layered with MeOH to afford the product as purple fibres (214 mg, 93 %).
1H NMR (400 MHz, CDCl3): d 10.25 (s, 2H, meso), 9.03 (d, J = 4 Hz, 2H, pyr Ha), 8.08 (d, J = 4 Hz, 2H, pyr Hb), 8.05 (d, J = 8 Hz, 2H, Ar), 7.90 (d, J = 8 Hz, 2H, Ar), 3.98 (t, J = 8 Hz, 8H, hex H1), 3.34 (s, 1H, CCH), 2.52 (s, 6H, CH3), 2.51 (s, 6H, CH3), 2.19 (m, 8H, hex H2), 1.73 (m, 8H, hex H3), 1.47 (m, 8H, hex H4), 1.36 (m, 8H, hex H5), 0.90 (t, J = 7 Hz, 12H, hex H6), -2.42 (s, 2H, NH).
5-(4-Methoxycarbonyl-phenyl)-15-(3,5-diiodo-phenyl)-2,8,12,18-tetrahexyl-3,7,13,17-tetramethyl porphyrin (156)
Prepared according to the standard procedure from 153 and 4-formyl-methyl-benzoate. The product was isolated by chromatography on silica eluted with hexane/EA/CHCl3 (20/1/1) with a gradient to hexane/EA (10/1). Recrystallization from CHCl3 layered with MeOH afforded the product as purple crystals (0.45 g, 16 %). Rf 0.33 (hexane/CHCl3/EA, 20/1/1).
1H NMR (500 MHz, CDCl3): d 10.25 (s, 2H, meso), 8.53 (s, 1H, ArH4), 8.46 - 8.44 (m, 4H, Ar), 8.18 (d, J = 8 Hz, 2H, Ar), 4.14 (s, 3H, OCH3), 3.98 (m, 8H, hex H1), 2.59 (s, 6H, CH3), 2.46 (s, 6H, CH3), 2.19 (m, 8H, hex H2), 1.74 (m, 8H, hex H3), 1.48 (m, 8H, hex H4), 1.38 (m, 8H, hex H5), 0.91 (m, 12H, hex H6), -2.45 (s, 1H, NH), -2.48 (s, 1H, NH); 13C NMR (100.6 MHz, CDCl3): d 167.4, 147.3, 146.2, 145.0, 144.6, 144.5, 144.0, 143.8, 141.7, 141.6, 141.1, 136.0, 135.5, 133.1, 130.1, 128.8, 117.0, 114.3, 97.5, 93.8, 52.5, 2 ´ 33.3, 32.0, 30.1, 30.0, 2 ´ 26.8, 22.8, 22.7, 15.5, 14.9, 14.2, 14.1; UV/vis (DCM): lmax 410, 508, 542, 574, 626 nm; ES MS: m/z [M]+ 1165; IR (CCl4): nmax 2956 (s), 2930 (s), 2858 (s), 1728 (s) cm–1; Anal. Calcd for C62H78N4O2I2: C 63.80, H 6.74, N 4.80. Found: C 63.80, H 6.68, N 4.70.
5-(4-Methoxycarbonyl-phenyl)-15-(3,5-diiodo-phenyl)-2,8,12,18-tetrahexyl-3,7,13,17-tetramethyl porphyrinato nickel(II) (157)
156 was nickel metallated according to the standard procedure. The product was recrystallized from CHCl3 layered with MeOH. Fibrous red crystals (91 mg, 87 %).
1H NMR (500 MHz, CDCl3): d 9.46 (s, 2H, meso), 8.41 (m, 1H, ArH4), 8.33 (d, J = 8 Hz, 2H, ArCO2), 8.22 (d, J = 1 Hz, 2H, ArH2), 7.96 (d, J = 8 Hz, 2H, ArCO2), 4.08 (s, 3H, CO2CH3), 3.66 (m, 8H, hex H1), 2.33 (s, 6H, CH3), 2.20 (s, 6H, CH3), 2.00 (m, 8H, hex H2), 1.62 (m, 8H, hex H3), 1.45 (m, 8H, hex H4), 1.36 (m, 8H, hex H5), 1.82 (m, 12H, hex H6); 13C NMR (100.6 MHz, CDCl3): d 167.2, 146.3, 145.3, 2 ´ 144.7, 144.5, 141.2, 140.0, 139.8, 139.7, 139.6, 138.6, 138.1, 133.2, 130.0, 128.7, 115.6, 113.0, 96.8, 93.6, 52.3, 2 ´ 32.8, 31.9, 29.8, 29.7, 2 ´ 26.3, 2 ´ 22.7, 16.0, 15.5, 2 ´ 14.1; UV/vis (DCM): lmax 408, 528, 564 nm; LSI MS: m/z [M]+ 1225; IR (CCl4): nmax 2956 (s), 2930 (s), 2860 (m), 1728 (s), 1274 (s) cm–1; Anal. Calcd for C62H76N4O2I2Ni: C 60.95, H 6.27, N 4.59. Found: C 61.02, H 6.32, N 4.68.
Me ester fb wedge (158)
AsPh3 (26 mg, 85 mmol), Pd2(dba)3 (12 mg, 13 mmol), 155 (75 mg, 86 mmol) and 156 (50 mg, 43 mmol) were mixed and DCM (dry, 3 mL) and Et3N (dry, 3 mL) added. The mixture was degassed and stirred under Ar at rt for 36 h. DCM (50 mL) was added to the red suspension. The solution was washed with water (3 ´ 30 mL), dried (MgSO4) and evaporated to a red solid. After column chromatography on a short (10 cm) silica column eluted with CHCl3/MeOH (50/1) and precipitation from CHCl3 solution by addition of MeOH the product was obtained as a red solid (85 mg, 75 %). Rf 0.41 (CHCl3/MeOH, 50/1).
1H NMR (400 MHz, CDCl3): d 10.33 (s, 2H, meso), 10.26 (s, 4H, meso), 9.01 (d, J = 6 Hz, 4H, pyr Ha), 8.53 (s, 3H, Ar), 8.46 (d, J = 8 Hz, 2H, Ar), 8.21 (d, J = 8 Hz, 2H, Ar), 8.11 (d, J = 8 Hz, 4H, Ar), 8.06 - 8.02 (m, 8H, Ar), 4.15 - 3.98 (m, 27H, OCH3, hex H1), 2.87 (s, 6H, CH3), 2.57 (s, 12H, CH3), 2.51, 2.50 (both s, 18H, CH3), 2.35 - 2.14 (m, 24H, hex H2), 1.89 - 1.32 (m, 72H hex H3-5), 1.00 - 0.88 (m, 36H, hex H6), -2.29, -2.33, -2.40 (br s, total 6H, NH); 13C NMR (100.6 MHz, CDCl3): d 167.4, 150.8, 149.0, 147.4, 145.1, 145.0, 144.6, 144.0, 143.9, 143.8, 143.7, 143.3, 142.8, 141.8, 2 ´ 141.7, 141.5, 136.2, 2 ´ 135.9, 135.3, 134.6, 133.2, 133.1, 133.0, 131.1, 130.1, 128.8, 128.5, 123.3, 123.0, 117.4, 116.9, 115.9, 114.4, 97.4, 90.8, 89.8, 52.4, 33.4, 33.3, 32.1, 2 ´ 32.0, 30.1, 2 ´ 30.0, 26.9, 26.8, 2 ´ 22.8, 22.7; UV/vis (DCM): 412, 508, 542, 574, 626 nm; MALDI MS: m/z [M]+ 2670.
Acid fb wedge (159)
KOH (100 mg, 1.8 mmol) and 158 (36 mg, 13 mmol) were stirred in a mixture of THF (10 mL) and water (100 mL) at 40 °C for 32 h to form a red suspension. Additional portions of KOH (25 mg, 0.45 mmol), water (200 mL) and THF (10 mL) were added and the mixture refluxed for 18 h under N2. After cooling, water (30 mL) and CHCl3 (50 mL) were added and HCl (3 N) added until the organic layer became green. The organic phase was separated and washed with water (3 ´ 30 mL), dried (MgSO4) and evaporated to a red solid. Column chromatography on silica eluting with CHCl3 gradient to CHCl3/MeOH (20/1) followed by precipitation from CHCl3 solution by addition of hexane afforded the product as a deep purple solid (15 mg, 42 %). Rf 0.50 (CHCl3/MeOH, 10/1).
1H NMR (400 MHz, CDCl3): d 10.35 (s, 2H, inner meso), 10.26 (s, 4H, outer meso), 9.04 (d, J = 4 Hz, 4H, pyr Ha), 8.58 (d, J = 8 Hz, 2H, Ar), 8.53 (s, 3H, Ar), 8.28 (d, J = 8 Hz, 2H, Ar), 8.12 - 8.03 (m, 12H, Ar), 4.11, 3.99 (br m, 24H, hex H1), 2.87 (s, 6H, CH3), 2.57 (s, 12H, CH3), 2.54 (s, 6H, CH3), 2.51 (s, 12H, CH3), 2.35 - 2.14 (m, 24H, hex H2), 1.89 - 1.68 (m, 24H, hex H3), 1.62 (m, 48H, hex H4,5), 1.00 - 0.88 (m, 36H, hex H6), -2.33 (br, NH). 13C NMR (125.7 MHz, CDCl3): d 148.7, 145.0, 144.6, 144.0, 143.9, 143.8, 143.8, 142.8, 141.7, 141.5, 136.2, 135.9, 135.2, 133.3, 133.1, 131.1, 129.3, 128.5, 123.3, 122.9, 117.4, 114.2, 97.3, 90.7, 89.7, 33.2, 2 ´ 32.0, 31.9, 30.1, 29.9, 26.7, 22.8, 2 ´ 22.7, 15.6, 15.0, 14.9, 14.1 (2 peaks). UV/vis (DCM): 412, 508, 540, 574 nm; ES MS: m/z [M]+ 2657.
Me ester Ni/fb wedge (160)
Prepared analogously to 158 but substituting 156 with 157. The product was purified by silica gel chromatography eluting with DCM/EA (10/1), followed by a second column eluted with CHCl3/MeOH (50/1). The product was obtained as a red solid (99 mg, 89 %). Rf 0.34 (CHCl3/MeOH, 50/1).
1H NMR (400 MHz, CDCl3): d 10.27 (s, 4H, fb meso), 9.51 (s, 2H, Ni meso), 8.98 (d, J = 6 Hz, 4H, pyr Ha), 8.44 (d, J = 2 Hz, 1H, Ar), 8.36 (d, J = 8 Hz, 2H, Ar), 8.31 (d, J = 2 Hz, 2H, Ar), 8.08 (d, J = 8 Hz, 4H, Ar), 8.01 (m, 10H, Ar), 4.11 (s, 3H, OCH3), 3.99 (m, 16H, hex H1), 3.77 (t, J = 7 Hz, 4H, hex H1), 3.66 (t, J = 8 Hz, 4H, hex H1), 2.62 (s, 6H, CH3), 2.56 (s, 12H, CH3), 2.49 (s, 12H, CH3), 2.24 - 2.01 (m, 30H, CH3, hex H2), 1.79 - 1.34 (m, 72H, hex H3-5), 1.02 - 0.90 (m, 36H, hex H6), -2.39 (s, 4H, NH); 13C NMR (125.7 MHz, CDCl3): d 167.3, 150.7, 149.0, 146.4, 145.0, 144.5, 144.4, 143.9, 143.7, 142.8, 142.3, 141.7, 141.5, 140.4, 139.9, 2 ´ 139.7, 138.5, 136.2, 135.9, 135.2, 134.5, 133.2, 133.0, 131.0, 129.9, 128.6, 128.4, 123.1, 122.9, 117.4, 115.4, 114.6, 114.3, 97.3, 96.7, 90.7, 89.7, 52.3, 33.3, 33.0, 32.8, 2 ´ 31.9, 2 ´ 29.9, 29.8, 26.8, 26.4, 26.3, 22.8, 22.7, 16.2, 15.5, 14.9, 14.2, 14.1; UV/vis (DCM): 412, 508, 570 nm; MALDI MS: m/z [M]+ 2727.
Acid Ni/fb acid wedge (161)
A mixture of KOH (10 mL) and 160 (42 mg, 15 mmol) was refluxed in THF (10 mL) and water (500 mL) under N2 for 13 h. After cooling to rt, water (30 mL) was added to produce a red precipitate. DCM (50 mL) was added followed by dropwise addition of HCl (3 N) until the precipitate had been solubilized. The red organic layer was washed with water (3 ´ 30 mL), dried and evaporated to a red solid. After chromatography on a short (5 cm) silica column eluted with toluene/MeOH (100/1 gradient to 10/1) the product was obtained as a red solid (38 mg, 90 %). Rf 0.15 (toluene/MeOH, 10/1).
1H NMR (400 MHz, CDCl3): d 10.27 (s, 4H, fb meso), 9.54 (s, 2H, Ni meso), 9.04 (d, J = 4 Hz, 4H, pyr Ha), 8.43 (m, 3H, Ar), 8.30 (d, J = 1 Hz, 2H, Ar), 8.11 - 8.00 (m, 14H, Ar), 3.99 (br, 16H, fb hex H1), 3.79 (br, 4H, Ni hex H1), 3.70 (br, 4H, Ni hex H1), 2.61 (s, 6H, Ni CH3), 2.57 (s, 12H, fb CH3), 2.51 (s, 12H, fb CH3), 2.29 (s, 6H, Ni CH3), 2.19 (m, 16H, fb hex H2), 2.07 (m, 8H, Ni hex H2), 1.78 - 1.63 (m, 24H, hex H3), 1.57 - 1.33 (m, 48H, hex H4,5), 0.99 (t, J = 7 Hz, 6H, Ni hex H6), 0.95 (t, J = 7 Hz, 6H, Ni hex H6), 0.91 (t, J = 7Hz, 24H, fb hex H6), -2.3 (br, NH); 13C NMR (100.6 MHz, CDCl3): d 170.3, 151.4, 148.4, 146.6, 145.0, 144.6, 144.4, 144.0, 143.9, 143.7, 142.7, 142.5, 141.8, 141.5, 140.4, 140.0, 139.7, 138.6, 138.5, 136.2, 135.9, 135.2, 133.4, 133.0, 131.1, 129.2, 128.6, 123.2, 123.0, 117.5, 115.6, 114.6, 114.1, 97.4, 96.8, 90.8, 89.7, 33.4, 33.1, 32.9, 2 ´ 32.0, 30.0, 29.9, 29.7, 29.4, 26.8, 26.4, 22.9, 2 ´ 22.8, 16.3, 15.6, 15.0, 14.9, 14.3, 2 ´ 14.2. UV/vis (DCM): 412, 508, 570, 626 nm; MALDI MS: m/z [M]+ 2712.
(118)2 · NH2NH2 (166)
Hydrazine monohydrate (0.5 mL, 10 mmol) in water (10 mL) was added to a mixture of a solution of 118 (10 mg, 9.2 mmol) in DCM (1 mL) and water (5 mL). After 150 min at rt an additional portion of DCM (20 mL) was added and the organic layer separated, washed with water (2 ´ 30 mL) and dried (MgSO4). Evaporation of the solvent afforded the product as an orange solid (5 mg, 49 %).
Crystals of 166 for structure determination were obtained from a solution of 166 and 118 · N2H4 in toluene layered with MeOH.
1H NMR (400 MHz, CDCl3): d 9.37 (s, 4H, meso), 7.84 (m, 8H, Ar), 7.55 (m, 8H, Ar), 7.25 (m, Ar), 3.72 (m, 16H, hex H1), 2.24 (s, 24H, CH3), 2.04 (m, 16H, hex H2), 1.84 (m, 16H, hex H3), 1.63 (m, 16H, hex H4), 1.52 (m, 16H, hex H5), 1.05 (t, J = 7 Hz, 24H, hex H6), -11.03 (s, 4H, NH2); 13C NMR (100.6 MHz, CDCl3): d 143.5, 141.6, 138.6, 138.0, 137.8, 133.0, 132.9, 128.5, 127.6, 127.3, 118.3, 96.8, 33.4, 31.9, 30.5, 27.0, 22.9, 15.1, 14.2; UV/vis (DCM): lmax 360, 408, 528, 558 nm. IR (CCl4): nmax 3287 (w), 3230 (w), 3147 (w) 2957 (s), 2930 (s), 2858 (m), 1466 (m) cm–1.
(118)2 · NHMeNHMe (167)
A solution of 168 (10 mg, 8.7 mmol) in DCM/hexane (1/1) was passed through a silica column. The solvent was evaporated to afford the product as an orange solid (7.1 mg, 73 %).
Crystals for structure determination were obtained from a DCM solution layered with MeOH.
1H NMR (400 MHz, CDCl3): d 9.64 (s, 4H, meso), 7.79 (m, 12H, Ar), 7.53 (m, 8H, Ar), 4.17 (m, 4H, hex H1), 4.05 (m, 4H, hex H1), 3.79 (m, 8H, hex H1), 2.32 (s, 12H, CH3), 2.29 (s, 12H, CH3), 1.96 (m, 4H, hex H2), 1.85 (m, 12H, hex H2), 1.65 (m, 16H, hex H3), 1.47 - 1.33 (m, 32H, hex H4,5), 0.93, 0.90 (2 ´ t, J = 7 Hz, 24H, hex H6), -7.32 (d, J = 6 Hz, 6H, NHCH3), -9.40 (t, J = 6 Hz, 2H, NHCH3).
118 · NHMeNHMe (168)
To a solution of 118·MeOH (12.2 mg, 11 mmol) in DCM (20 mL) was added N,N'-dimethyl hydrazine dihydrochloride (17.3 mg, 0.13 mmol) in water (20 mL). NaOH (10 %, 2 drops) was added and the mixture shaken. The organic phase was separated, dried (MgSO4) and evaporated to an orange solid (10.6 mg, 85 %).
1H NMR (400 MHz, CDCl3): d 10.28 (s, 2H, meso), 8.10 (m, 2H, Ar), 8.04 (m, 2H, Ar), 7.76 (m, 6H, Ar), 4.03 (m, 4H, hex H1), 3.91 (m, 4H, hex H1), 2 ´ 2.48 (s, 12H, CH3), 2.21 (m, 8H, hex H2), 1.77 (m, 8H, hex H3), 1.52 (m, 8H, hex H4), 1.41 (m, 8H, hex H5), 2 ´ 0.92 (t, J = 7 Hz, hex H6), -0.66 (s, 3H, NHCH3), -3.27 (d, J = 6 Hz, 3H, RhNHCH3), -4.09 (s, 1H, NHCH3), -4.90 (q, J = 5 Hz, 1H, RhNHCH3); 13C NMR (100.6 MHz, CDCl3): d 2 ´ 144.3, 142.7, 140.5, 140.4, 140.1, 140.0, 138.8, 138.7, 133.8, 133.0, 128.3, 127.7, 127.3, 119.5, 98.9, 34.3, 33.8, 2 ´ 33.3, 32.0, 2 ´ 30.1, 2 ´ 27.0, 22.7, 15.5, 14.1.
(118)2 · NHMeNH2 (169)
Prepared by titration of a solution of 118·MeOH (4.2 mg, 3.8 mmol) with methyl hydrazine in CDCl3. After the titration the sample was eluted through a silica column with hexane/DCM (1/1) and evaporated to an orange solid. This was dissolved in DCM and layered with MeOH to obtain crystals for structure determination.
1H NMR (400 MHz, CDCl3): d 9.47 (s, 2H, meso), 9.43 (s, 2H, meso), 7.93 (d, J = 7 Hz, 2H, Ar), 7.82 (m, 8H, Ar), 7.52 (m, 8H, Ar), 7.33 (d, J = 4 Hz, 2H, Ar), 4.03 (m, 4H, hex H1), 3.89 (m, 4H, hex H1), 3.75 (m, 4H, hex H1), 3.66 (m, 4H, hex H1), 2.33 (s, 6H, CH3), 2 ´ 2.27 (2 ´ s, 18H, CH3), 2.17 - 1.34 (m, 64H, hex H2-5), 0.96 (m, 24H, hex H6), -7.79 (d, J = 6 Hz, 3H, NHCH3), -10.00 (d, J = 12 Hz, 2H, NH2), -10.34 (m, 1H, NHCH3).
(118)2 · NH2NMe2 (170)
Prepared by titration of a solution of 118·MeOH (4.0 mg, 3.6 mmol) with N,N-dimethyl hydrazine in CDCl3.
Material for crystal growth was prepared by passing a solution of 118 (5.2 mg, 4.8 mmol) and N,N-dimethyl hydrazine (1 mL, 13 mmol) in DCM (0.5 mL) and hexane (0.5 mL) through a silica column. Porphyrin was washed from the column with DCM/hexane (1/1) and the solvent evaporated. X-ray quality crystals were obtained from a DCM solution layered with MeOH.
1H NMR (400 MHz, CDCl3): d 9.77 (s, 2H, meso), 0.37 (s, 2H, meso), 7.80 (m, 12H, Ar), 7.62 (m, 6H, Ar), 7.37 (d, J = 7 Hz, 2H, Ar), 4.04 (m, 8H, hex H1), 3.76 (m, 8H, hex H1), 2.38 (s, 12H, CH3), 2.29 (s, 12H, CH3), 1.85 (m, 16H, hex H2), 1.63 (m, 16H, hex H3), 1.50 - 1.30 (m, 32H, hex H4,5), 0.93 (t, J = 7 Hz, 12H, hex H6), 0.88 (t, J = 7 Hz, 12H, hex H6), -7.83 (s, 6H, NCH3), -10.24 (s, 2H, NH2).
118 · EtSH (171)
To a solution of 118 (10 mg, 9.2 mmol) in CHCl3 (1 mL) was added EtSH (10 mL, 0.14 mmol). After stirring for several minutes the solvent was evaporated and the residues dried in vacuo to afford 171 as an orange solid in quantitative yield.
1H NMR (250 MHz, CDCl3): d 10.21 (s, 2H, meso), 8.04 (m, 4H, Ar), 7.72 (m, 6H, Ar), 3.95 (m, 8H, hex H1), 2.47 (s, 12H, CH3), 2.19 (m, 8H, hex H2), 1.76 (m, 8H, hex H3), 1.56 - 1.31 (m, 16H, hex H4,5), 0.91 (t, J = 7 Hz, 12H, hex H6), -1.29 (t, J = 7 Hz, 3H, CH3CH2S), -2.86 (m, 2H, CH2S), -4.29 (t, J = 7 Hz, 1H, SH).
118 · DMSO (172)
Prepared by titration of a solution of 118 in CDCl3 with DMSO in CDCl3.
Crystals for structure determination were grown by layering a solution of 118 in DCM with a mixture of DMSO and MeOH.
1H NMR (250 MHz, CDCl3): d 10.28 (s, 2H, meso), 8.12 (d, J = 7 Hz, 2H, Ar), 7.95 (d, J = 8 Hz, 2H, Ar), 7.73 (m, 6H, Ar), 3.95 (m, 8H, hex H1), 2.47 (s, 12H, CH3), 2.17 (m, 8H, hex H2), 1.75 (m, 8H, hex H3), 1.55 - 1.30 (m, 16H, hex H4,5), 0.90 (t, J = 7 Hz, 12H, hex H6), -2.23 (s, 6H, CH3S).
118 · Me2S (173)
To a solution of 118 (11 mg, 10 mmol) in DCM (1 mL) was added Me2S (10 mL). After stirring for 20 min, the solution was chromatographed on silica gel eluted with DCM. The orange eluent was collected and evaporated to afford 172 as an orange solid (1.3 mg, 11 %).
1H NMR (400 MHz, CDCl3): d 10.21 (s, 2H, meso), 8.10 (d, J = 7 Hz, 2H, Ar), 7.97 (d, J = 8 Hz, 2H, Ar), 7.78 (m, 2H, Ar), 7.70 (m, 4H, Ar), 3.99 (m, 4H, hex H1), 3.88 (m, 4H, hex H1), 2.45 (s, 12H, CH3), 2.17 (m, 8H, hex H2), 1.74 (m, 8H, hex H3), 1.49 (m, 8H, hex H4), 1.38 (m, 8H, hex H5), 0.89 (t, J = 7 Hz, 12H, hex H6), -3.12 (d, J = 1 Hz, 6H, CH3S).
Isonicotinic acid 11-bromo-undecyl ester (174)
Isonicotinic acid (0.50 g, 4.1 mmol) was refluxed in thionyl chloride (10 mL) under an argon atmosphere for 3 h. Excess thionyl chloride was removed by distillation and the resulting oil dried in vacuo. To this was added 11-bromo-1-undecanol (0.90 g, 3.6 mmol) in DCM (10 mL). The solution was refluxed for 1 h under argon. After cooling to room temperature, CHCl3 (20 mL) was added and the solution washed with satd. Na2CO3, dried (MgSO4) and the solvent evaporated. The crude product was dissolved in Et2O (30 mL), filtered to remove yellow insoluble material, and the filtrate was acidified by dropwise addition of conc. H2SO4. The resulting precipitates were filtered, washed repeatedly with Et2O, then shaken with CHCl3 (20 mL), water (5 mL) and satd. Na2CO3. The organic phase was separated, washed with dil. Na2CO3 (10 mL), dried (MgSO4) and evaporated to a cream solid (0.97 g, 76 %). Rf 0.30 (hexane/EA, 3/1).
1H NMR (250 MHz, CDCl3): d 8.75 (dd, J = 4, 2 Hz, 2H, pyr H2), 7.82 (dd, J = 4, 2 Hz, 2H, pyr H3), 4.33 (t, J = 7 Hz, 2H, OCH2), 3.38 (t, J = 7 Hz, 2H, CH2Br), 1.88 - 1.73 (m, 4H, CH2), 1.42 - 1.27 (m, 14H, CH2); 13C NMR (62.9 MHz, CDCl3):d 165.1, 150.6, 137.6, 122.8, 65.9, 39.94, 32.8, 2 ´ 29.4, 29.2, 28.7, 28.5, 28.1, 25.9; FAB MS: m/z [M+H]+ calcd 356.1225, found 356.1224; IR (CCl4): nmax 2930 (s), 2856 (s), 1732 (s), 1279 (s), 1121 (m) cm–1; Anal. Calcd for C17H26NO2Br: C 57.31, H 7.36, N 3.93. Found C 57.54, H 7.33, N 3.82.
Isonicotinic acid 11-thioacetyl-undecyl ester (175)
A solution of 174 (0.97 g, 2.7 mmol) and potassium thioacetate (0.34 g, 3.0 mmol) in PEG 400 (1.6 mL) was stirred at 50 °C under nitrogen for 3 h. To this was added water (10 mL) and CHCl3 (20 mL). The organic layer was separated and washed with water (10 mL), dried (MgSO4) and evaporated to a brown oil which solidified on standing. After column chromatography on silica eluted with hexane/EA (3/1) the product was obtained as a cream coloured solid (0.76 g, 79 %). Rf 0.25 (hexane/EA, 3/1).
1H NMR (250 MHz, CDCl3): d 8.74 (dd, J = 4, 2 Hz, 2H, pyr H2), 7.81 (dd, J = 4, 2 Hz, pyr H3), 4.32 (t, J = 6.7 Hz, 2H, OCH2), 2.82 (t, J = 7 Hz, 2H, SCH2), 2.28 (s, 3H, CH3), 1.74 (m, 2H, CH2), 1.53 (m, 2H, CH2), 1.39 - 1.25 (m, 14H, CH2); 13C NMR (100.6 MHz, CDCl3): d 196.0, 165.2, 150.6, 137.6, 122.8, 65.9, 30.6, 29.5, 29.4, 29.4, 29.2, 2 ´ 29.1, 28.8, 28.6, 25.9, 25.8; ES MS: m/z [M+H]+ 352; IR (CCl4): nmax 2928 (s), 2856 (m), 1732 (s), 1694 (s), 1279 (s) cm–1; Anal. Calcd for C19H29O3SN: C 64.92, H 8.32, N 3.98. Found: C 64.94, H 8.30, N 3.94; mp 47 - 49 °C.
Nicotinic acid 11-bromo-undecyl ester (176)
Prepared analogously to 174 except using nicotinic acid. Cream solid (0.82 g, 64 %). Rf 0.30 (hexane/EA, 3/1).
1H NMR (250 MHz, CDCl3): d 9.20 (dd, J = 2, 1 Hz, 1H, pyr H2), 8.75 (dd, J = 5, 2 Hz, 1H, pyr H6), 8.27 (dt, J = 8, 2 Hz, 1H, pyr H4), 7.36 (m, 1H, pyr H5), 4.32 (t, J = 7 Hz, 2H, OCH2), 3.37 (t, J = 7 Hz, 2H, CH2Br), 1.89 - 1.70 (m, 4H, CH2), 1.42 - 1.19 (m, 14H, CH2); 13C NMR (100.6 MHz, CDCl3): d 165.3, 153.3, 150.9, 137.0, 126.4, 123.3, 65.6, 34.2, 32.8, 29.4, 2 ´ 29.4, 29.2, 28.7, 28.6, 28.2, 26.0, 25.8; EI MS: m/z [M-Br]+ calcd 276.1963, found 276.1971; IR (CCl4): nmax 2930 (s), 2856 (s), 1727 (s), 1284 (s) cm–1; Anal. Calcd for C17H26NO2Br: C 57.31, H 7.36, N 3.93. Found C 57.46, H 7.41, N 3.89.
Nicotinic acid 11-thioacetyl-undecyl ester (177)
Prepared analogously to 175, except starting from 176.White crystalline solid (0.76 g, 73 %). Rf 0.25 (hexane/EA, 3/1).
1H NMR (250 MHz, CDCl3) d 9.21 (d, J = 1 Hz, 1H, pyr H2), 8.75 (dd, J = 5, 2 Hz, 1H, pyr H6), 8.28 (dt, J = 8, 2 Hz, 1H, pyr H4), 7.37 (m, 1H, pyr H5), 4.33 (t, J = 7 Hz, 2H, OCH2), 2.84 (t, J = 7 Hz, 2H, SCH2), 2.30 (s, 3H, CH3), 1.76 (m, 2H, CH2), 1.54 (m, 2H, CH2), 1.44 - 1.26 (m, 14H, CH2); 13C NMR (100.6 MHz, CDCl3): d 196.0, 165.4, 153.3, 150.9, 137.0, 126.4, 123.3, 65.6, 30.6, 29.5, 29.5, 29.4, 29.2, 29.1, 29.1, 28.8, 28.6, 26.0; ES MS: m/z [M+H]+ 352; IR (CCl4): nmax 2930 (s), 2856 (s), 1726 (s), 1694 (s) cm–1; Anal. Calcd for C19H29O3SN: C 64.92, H 8.32, N 3.98. Found: C 64.50, H 8.36, N 3.99; mp 42 - 43 °C.
11-Mercapto undecanol (178)351
A solution of 11-bromoundecanol (2.00 g, 7.96 mmol) and thiourea (0.73 g, 9.59 mmol) in EtOH (25 mL) was degassed then refluxed under N2 for 18 h. After cooling to rt, NaOH (10 % aq, 20 mL) was added, the solution degassed then refluxed for 2 h under N2. After cooling, HCl (3 N, 40 mL) was added and the solution extracted with DCM (4 ´ 30 mL). The combined extracts were washed with satd. NaHCO3 (20 mL), dried (MgSO4) and evaporated to afford the product as a white solid which was used without purification (1.49 g, 92 %). Rf 0.33 (hexane/EA, 5/1).
1H NMR (250 MHz, CDCl3): d 3.62 (t, J = 7 Hz, 2H, OCH2), 2.50 (t, J = 7 Hz, 2H, SCH2), 1.64 - 1.26 (m, 20H, (CH2)9, SH, OH).
Disulfanyl bis-(11-undecanol) (179)338,352
NaBO3·H2O (0.98 g, 9.8 mmol) and 178 (1.00 g, 4.9 mmol) were stirred in MeOH (15 mL) and water (2.5 mL) for 220 min at rt. The solvent was evaporated and water (50 mL) added. The suspension was extracted with CHCl3 (2 ´ 100 mL), the combined extracts washed with satd. Na2CO3 (20 mL), dried (MgSO4) and evaporated to yield the product as a white solid which did not require further purification (0.92 g, 92 %).
1H NMR (250 MHz, CDCl3): d 3.63 (br m, 4H, OCH2), 2.67 (t, J = 7 Hz, 4H, SCH2), 1.63 (m, 4H, CH2), 1.56 (m, 4H, CH2), 1.39 - 1.24 (m, 30H, (CH2)7, OH); Anal. Calcd for C22H46O2S2: C 64.97, H 11.40. Found: C 65.16, H 11.29.
Disulfanyl bis(11-undecyl-isonicotinate) (180)
Isonicotinic acid (0.91 g, 7.4 mmol), DMAP (60 mg, 0.50 mmol) and 179 (1.00 g, 2.5 mmol) were mixed and DCM (10 mL) added. To this suspension was added a solution of EDC (1.42 g, 7.4 mmol) in a mixture of DCM (10 mL) and DMF (10 mL) over 1 min. The suspension was stirred for 16 h at rt during which time it cleared. Further portions of EDC (0.47 g, 2.4 mmol) and isonicotinic acid (0.30 g, 2.4 mmol) were added. Stirring was continued for an additional 4 h, after which DCM (30 mL) was added and the solution washed with water (50 mL), satd. NaHCO3 (30 mL), dried (MgSO4) and evaporated onto silica gel which was loaded onto a silica column. Elution with hexane/EA (1/1) furnished the product as a white solid (1.25 g, 84 %). Rf 0.42 (hexane/EA, 1/1).
Crystals for structure determination were obtained from a DCM solution layered with MeOH.
1H NMR (500 MHz, CDCl3): d 8.76 (d, J = 5 Hz, 4H, pyr H2), 7.82 (d, J = 5 Hz, 4H, pyr H3), 4.33 (t, J = 6.7 Hz, 4H, OCH2), 2.66 (t, J = 7.3 Hz, 4H, SCH2), 1.76 (m, 4H, CH2), 1.65 (m, 4H, CH2), 1.43 - 1.27 (m, 28H, (CH2)7); 13C NMR (62.9 MHz, CDCl3): d 165.2, 150.6, 137.6, 122.8, 65.9, 39.1, 29.4, 29.2, 28.6, 28.5, 25.9; FAB MS: m/z [M+H]+ calcd 617.3447, found 617.3423; IR (CCl4): nmax 2928 (s), 2855 (m), 1732 (s), 1279 (s) cm–1; Anal. Calcd for C34H52N2O4S2: C 66.20, H 8.50, N 4.54. Found: C 66.29, H 8.54, N 4.61; mp 40 - 42 °C.
Disulfanyl bis(11-undecyl-nicotinate) (181)
Prepared analogously to 180 except using nicotinic acid. White solid (1.27 g, 84 %). Rf 0.49 (hexane/EA, 1/1).
1H NMR (250 MHz, CDCl3): d 9.21 (dd, J = 2, 1 Hz, 2H, pyr H2), 8.75 (dd, J = 5, 2 Hz, 2H, pyr H6), 8.27 (dt, J = 8, 2 Hz, 2H, pyr H4), 7.37 (ddd, J = 8, 5, 1 Hz, 2H, pyr H5), 4.33 (t, J = 7 Hz, 4H, OCH2), 2.65 (t, J = 7 Hz, 4H, CH2S), 1.78 (m, 4H, CH2), 1.67 (m, 4H, CH2), 1.40 - 1.27 (m, 28H, (CH2)7); 13C NMR (62.9 MHz, CDCl3): d 165.3, 153.3, 150.9, 137.0, 126.3, 123.2, 65.6, 39.1, 29.5, 29.2, 28.6, 28.5, 26.0; FAB MS: m/z [M+H]+ calcd 617.3447, found 617.3389; IR (CCl4): nmax 2927 (s), 2855 (s), 1727 (s), 1591 (m), 1284 (s), 1121 (m) cm–1; Anal. Calcd for C34H52N2O4S2: C 66.20, H 8.50, N 4.54. Found: C 66.16, H 8.52, N 4.50; mp 63 - 65 °C.
12-Thioacetyl-dodecanoic acid (182)
12-Bromododecanoic acid (1.50 g, 5.37 mmol) and KSCOCH3 (1.23 g, 10.8 mmol) were stirred in PEG 400 (10 mL) at 40 °C for 1 h under N2. Water (50 mL) was added and the yellow suspension extracted with Et2O (2 ´ 100 mL). The combined organic extracts were washed with brine (25 mL), dried (MgSO4) and evaporated to a cream solid. Recrystallization from boiling hexane afforded the product as a white powder (1.20 g, 81 %). Rf 0.37 (hexane/EA, 3/1).
1H NMR (250 MHz, CDCl3): d 2.85 (t, J = 7 Hz, 2H, SCH2), 2.33, 2.31 (t and s, J = 7 Hz, 5H, CH2CO2 and CH3), 1.64 - 1.49 (m, 4H, CH2), 1.25 (br m, 14H, (CH2)7); 13C NMR (62.9 MHz, CDCl3): d 196.1, 179.8, 34.0, 30.6, 29.5, 2 ´ 29.4, 29.3, 29.2, 2 ´ 29.1, 29.0, 28.8, 24.6; FAB MS: m/z [M+H]+ calcd 275.1681, found 275.1682. IR (CCl4): nmax 3028 (br m), 2928 (s), 2856 (m), 1710 (s), 1684 (s) cm–1; Anal. Calcd for C14H26O3S: C 61.28, H 9.55. Found: C 61.55, H 9.53.
rac-12-Thioacetyl-dodecanoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester (183)
To a solution of DMAP (63 mg, 0.52 mmol), EDC (1.18 g, 6.20 mmol) and 182 (1.40 g, 5.17 mmol) in DCM at 0 °C (anhydrous, 10 mL) was added racemic 3-quinuclidinol (789 mg, 6.20 mmol) in DCM (10 mL) dropwise over 4 min. The solution was stirred at rt for 14 h, then the solvent evaporated. Water (30 mL) was added and the solution extracted with EA (3 ´ 50 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4) and evaporated to a white paste. This was chromatographed on silica eluted with CHCl3/MeOH (9/1). The product fractions were redissolved in hexane, filtered and the solvent evaporated to yield a colourless oil which solidified on standing (1.04 g, 53 %). Rf 0.3 (CHCl3/MeOH, 9/1).
1H NMR (250 MHz, CDCl3): d 4.77 (m, 1H, OCH), 3.21 (m, 1H), 2.88 - 2.61 (m, 7H), 2.29 (m, 5H, CH2S, CH2CO2), 1.96 (m, 1H), 1.80 (m, 1H), 1.61 - 1.46 (m, 6H), 1.35 - 1.24 (m, 15H); 13C NMR (62.9 MHz, CDCl3):d 196.0, 173.6, 71.0, 55.6, 47.4, 46.5, 34.5, 30.6, 29.5, 29.4, 29.2, 2 ´ 29.1, 28.8, 25.2, 25.0, 24.6, 19.6; FAB MS: m/z [M+H]+ calcd 384.2572, found 384.2565; IR (CCl4): nmax 2929 (s), 2855 (m), 1732 (s), 1694 (s) cm–1; Anal. Calcd for C21H37NO3S: C 65.76, H 9.72, N 3.65. Found: C 65.96, H 9.76, N 3.89.
(R) (-) 12-Thioacetyl-dodecanoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester ((R)(-) 183)
Prepared using the same procedure as the racemic compound, but using (R) (-) 3-quinuclidinol. White solid (0.91 g, 46 %).
Anal. Calcd for C21H37NO3S: C 65.76, H 9.72, N 3.65. Found: C 65.49, H 9.78, N 3.66.
rac-12-Mercapto-dodecanoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester (184)
Sodium methoxide (217 mg, 3.10 mmol) and 183 were placed under N2 and degassed MeOH (10 mL) added by cannula. The solution was stirred at rt for 30 min. Satd. NH4Cl (5 mL) was added, followed by water (45 mL) to form an emulsion which was extracted with EA (3 ´ 50 mL). The combined extracts were washed with brine (20 mL), dried MgSO4 and evaporated to an oil which was purified by chromatography on silica eluted with CHCl3/MeOH (10/1). The resulting white solids were dissolved in hot hexane, filtered and the solvent removed to afford the product as a white solid (536 mg, 62 %). Rf 0.43 (CHCl3/MeOH, 10/1).
1H NMR (250 MHz, CDCl3): d 4.78 (m, 1H, OCH), 3.22 (m, 1H), 2.89 - 2.61 (m, 6H), 2.50 (q, J = 7 Hz, 2H, CH2S), 2.30 (t, J = 7 Hz, CH2CO2), 1.98 (m, 1H), 1.81 (m, 1H), 1.70 - 1.49 (m, 6H), 1.38 - 1.25 (br m, 16H); 13C NMR (62.9 MHz, CDCl3): d 173.6, 70.9, 55.5, 47.4, 46.5, 34.5, 34.0, 29.4, 29.2, 29.1, 29.0, 28.3, 25.2, 25.0, 24.6, 24.5, 19.5; FAB MS: m/z [M+H]+ calcd 342.2467, found 342.2472; IR (CDCl3): nmax 2930 (s), 2856 (s), 1721 (s) cm–1; Anal. Calcd for C19H35O2NS: C 66.81, H 10.33, N 4.10. Found: C 66.81, H 10.29, N 4.10.
(R) (-) 12-Mercapto-dodecanoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester ((R) (-) 184)
Prepared using the same method as the racemic compound, except using enantiomerically pure 183.
Anal. Calcd for C19H35O2NS: C 66.81, H 10.33, N 4.10. Found: C 66.68, H 10.37, N 4.13.
Nicotinic acid undecyl ester (185)
Prepared analogously to 140 but using nicotinic acid. Colourless oil (0.77 g, 75 %). Rf 0.40 (hexane/EA, 3/1).
1H NMR (250 MHz, CDCl3): d 9.13 (dd, J = 2, 1 Hz, 1H, pyr H2), 8.66 (dd, J = 5, 2 Hz, 1H, pyr H6), 8.18 (dt, J = 8, 2 Hz, 1H, pyr H4), 7.27 (ddd, J = 8, 5, 1 Hz, 1H, pyr H5), 4.24 (t, J = 7 Hz, 2H, OCH2), 1.67 (m, 2H, CH2), 1.36 - 1.16 (m, 16H, (CH2)8). 0.77 (t, J = 7 Hz, 3H, CH3); 13C NMR (62.9 MHz, CDCl3): d 165.3, 153.3, 150.9, 136.9, 126.3, 123.2, 65.5, 31.9, 2 ´ 29.5, 29.3, 29.2, 28.6, 26.0, 22.6, 14.1; FAB MS: m/z [M+H]+ calcd 278.2120, found 278.2104; IR (CCl4): nmax 2956 (m), 2927 (s), 2855 (m), 1727 (s), 1283 (s) cm–1; Anal. Calcd for C17H27O2N: C 73.61, H 9.81, N 5.05. Found: C 73.70, H 9.84, N 5.11.
rac-Dodecanoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester (186)
To a solution of racemic 3-quinuclidinol (200 mg, 1.57 mmol) and Et3N (0.25 mL) in DCM (anhydrous, 2 mL) was added decanoyl chloride (290 mL, 1.40 mmol). The solution was stirred for 4 h, during which time a white precipitate formed. The solution was washed with satd. NaHCO3 (2 ´ 10 mL), brine (10 mL) and evaporated to a yellow paste. The product was columned on silica eluted with CHCl3/MeOH (10/1) to afford an inhomogenous material which was dissolved in hexane, filtered, and the solvent evaporated to afford the product as a colourless oil (110 mg, 28 %). Rf 0.32 (CHCl3/MeOH, 10/1).
1H NMR (250 MHz, CDCl3): d 4.76 (m, 1H, OCH), 3.21 (m, 1H), 2.89 - 2.53 (m, 5H), 2.28 (t, J = 7 Hz, 2H, CH2CO2), 1.96 (m, 1H), 1.80 (m, 1H), 1.67 - 1.55 (m, 4H), 1.39 - 1.23 (br m, 13H), 0.85 (t, J = 7 Hz, 3H, CH3); 13C NMR (62.9 MHz, CDCl3): d 173.6, 70.9, 55.5, 47.3, 46.4, 34.5, 31.8, 29.4, 29.2, 29.1, 25.2, 25.0, 24.5, 22.6, 19.5, 14.1; ES MS: m/z [M+H]+ calcd 282.2428, found 282.2412; IR (CCl4): nmax 2954 (s), 2930 (s), 2872 (m), 2856 (m), 1732 (s) cm–1; Anal. Calcd for C17H31O2N: C 72.55, H 11.10, N 4.98. Found: C 72.48, H 11.00, N 5.01.
3,3'-Dimethyl-4,4'-bipyridine (187)363
3-Picoline (9.7 mL, 0.16 mol) and chlorotrimethylsilane (12.5 mL, 0.10 mol) were added to THF (anhydrous, 50 mL). Sodium dispersion (30 wt % in toluene, 10 mL, + 25 mL THF) was added maintaining the temperature below 25 °C with an ice bath. After stirring for 6 h at rt under N2 the solvent was evaporated. The brown tar was extracted with boiling toluene (4 ´ 50 mL), and the extracts filtered. The toluene was evaporated and the residues dissolved in a mixture of acetone (75 mL) and water (75 mL). Solid KMnO4 was added portionwise until a purple colour persisted. A brown precipitate of MnO2 was filtered onto celite, and glucose was added to the filtrate to discharge the purple colour. The solution was filtered a further two times, the volume reduced by evaporation, then basified to pH 14 by addition of NaOH (10 % aq). The solution was extracted with CHCl3 (4 ´ 50 mL), the combined extracts dried (Na2SO4) and evaporated to a yellow oil. This was extracted with boiling hexane, then EA (several mL) added to the hexane extract. Concentration of this solution afforded the product as white crystals which were collected by filtration (930 mg, 6 %).
1H NMR (250 MHz, CDCl3): d 8.54 (s, 2H, H2), 8.49 (d, J = 5 Hz, 2H, H6), 7.00 (d, J = 5 Hz, 2H, H5), 2.05 (s, 6H, CH3).
4,4'-Bipyridine-3,3'-dicarboxylic acid (188)363
To a solution of 187 (914 mg, 4.96 mmol) in water (50 mL) at 90 °C was added KMnO4 (1.57 g, 9.94 mmol) portionwise over 20 min. The solution was stirred for 35 min at 90 °C, after which a further portion of KMnO4 (1.57 g, 9.94 mmol) was added over 15 min. The solution was stirred for 210 min at 90 °C, then KMnO4 (0.79 g, 5 mmol) added. After stirring for a further 4 h at 90 °C, the brown suspension was filtered through celite, and the residues washed with boiling water (150 mL). The filtrate was concentrated to 10 mL and the pH adjusted to 4 by dropwise addition of HCl (3 N) to afford a cloudy suspension. After standing in a refrigerator overnight the solid product was collected by filtration. An additional portion of product was obtained as colourless crystals by further concentration of the mother liquor and cooling to 0 °C for several hours. (346 mg, 29 %). The product was used without further purification.
Crystals suitable for structure determination were obtained from an aqueous solution.
4-Chloro-pyridine-3-carboxylic acid (189)368
4-chloropyridine was prepared by extraction of a solution of the hydrochloride salt (4.50 g, 0.03 mol) in satd. Na2CO3 (50 mL) with Et2O (4 ´ 50 mL). The combined Et2O layers were washed with brine (20 mL), dried (MgSO4) and concentrated to several mL.
LDA was prepared by addition of BuLi (15 % in hexane, 21 mL, ~34 mmol) to a solution of iPrNH2 (4.6 mL, 33 mL) in THF (anhydrous, 50 mL) at -79 °C under N2. The solution was stirred for 30 min, allowing to warm to 0 °C.
To a solution of the 4-chloropyridine in THF (300 mL) at -79 °C was added the LDA, also at -79 °C. After stirring for 20 min at -79 °C, CO2 was bubbled through the solution for 15 min, which was then allowed to warm to rt over 18 h. Several NaOH pellets were added, the THF evaporated and NaOH (2.5 M, 200 mL) added. The solution was extracted with DCM (2 ´ 50 mL), and the organic extracts discarded. The aqueous layer was acidified with conc. HCl, concentrated on the rotary evaporator until crystals formed. The crystals were filtered, and washed with water to afford the product as a cream powder (4.39 g, 93 %) which was used immediately.
4-Chloro-pyridine-3-carboxylic acid methyl ester (190)368
To a solution of 189 (4.38 g, 28 mmol), DMAP (0.50 g, 4.1 mmol), MeOH (5 mL) in DMF (40 mL) at 0 °C was added DCC (13.8 g, 67 mmol) in DMF (20 mL) over 5 min. The solution was stirred under N2 allowing to warm to rt over 4 h. A white precipitate was filtered off and the filtrate evaporated under reduced pressure. The residues were distilled (0.01 mmHg, 64 - 75 °C) to obtain a colourless solid which was further purified by chromatography on silica eluting with hexane/EA (3/1) to afford the product as a pale yellow solid (1.33 g, 28 %) which was stored at -20 °C. Rf 0.24 (hexane/EA, 3/1).
1H NMR (250 MHz, CDCl3): d 9.03 (s, 1H, H2), 8.57 (d, J = 5 Hz, 1H, H6), 7.40 (d, J = 5 Hz, 1H, H5), 3.96 (s, 3H, CH3); 13C NMR (62.9 MHz, CDCl3): d 164.3, 152.7, 152.3, 144.1, 125.9, 52.7; EI MS: m/z [M]+ calcd 171.0087, found 171.0084; IR (CDCl3): nmax 2955 (w), 1730 (s), 1295 (s), 1277 (s) cm–1.
4,4'-Bipyridine-3-carboxylic acid methyl ester (191)
A solution of 4-pyridyl-trimethyl-stannane (1.87 g, 7.73 mmol) and 190 (1.06 g, 6.18 mmol) in toluene (anhydrous, 100 mL) was added to LiCl (0.66 g, 16 mmol) and Pd(PPh3)4. The solution was degassed and heated at 110 °C under N2 in the dark for 42 h. After cooling and filtration the solution was evaporated to a yellow oil which solidified on standing. The product was chromatographed on silica eluted with EA, and recrystallized from boiling hexane to afford white needles (0.93 g, 70 %). NMR indicated a minor impurity which could not be removed by further recrystallization from water or hexane. Rf 0.19 (EA).
1H NMR (250 MHz, CDCl3): d 9.14 (s, 1H), 8.79 (d, J = 5 Hz, 1H), 8.68 (m, 2H), 7.26 - 7.22 (m, 3H), 3.73 (s, 3H, CH3); 13C NMR (62.9 MHz, CDCl3): d 166.1, 152.5, 151.4, 149.7, 147.8, 146.6, 125.4, 124.4, 122.7, 52.4; ES MS: m/z [M+H]+ calcd 215.0811, found 215.0821; Anal. Calcd for C12H10N2O2: C 67.28, H 4.70, N 13.08. Found C 66.76, H 4.66, N 12.76.
4,4'-Bipyridine-3-carboxylic acid (192)
NaOH (149 mg, 4.48 mmol) and 191 (900 mg, 4.21 mmol) were refluxed in water (2 mL) for 150 mL. After cooling to rt the pH was adjusted to 4 by addition of HCl (3 N) to form a white precipitate of product which was collected by filtration. Recrystallization from boiling MeOH afforded the product as a white powder (302 mg, 36 %).
1H NMR (400 MHz, CD3OD + CDCl3): d 9.14 (s, 1H, H2), 8.71 (d, J = 5 Hz, 1H, H6), 8.64 (dd, J = 5, 1 Hz, 2H, H2',6'), 7.53 (dd, J = 5, 1 Hz, 2H, H3',5'), 7.22 (dd, J = 5, 1 Hz, 1H, H5); 13C NMR (62.9 MHz, CD3OD + CDCl3): d 166.3, 152.7, 152.1, 151.6, 146.9, 144.7, 125.6, 124.9, 124.3.
4,4'-Bipyridyl-3-carboxylic acid 11-(11-hydroxy-undecyldisulfanyl)-undecyl ester (193)
Disulfanyl bis[11-undecyl-(4,4'-bipyridine-3-carboxylate)] (194)
A suspension of 192 (151 mg, 7.54 mmol), 179 (153 mg, 0.38 mmol), DMAP (9 mg, 0.07 mmol) and EDC (174 mg, 0.91 mmol) in DCM (4 mL) was stirred at rt for 2 d. After this time the suspension was evaporated on to silica gel and loaded on a column which was eluted with hexane/EA (1/1) to elute unreacted 179, followed by a gradient to EA then EA/MeOH (9/1) to elute the products.
Data for 193. White solid (60 mg). Rf 0.53 (EA).
1H NMR (250 MHz, CDCl3): d 9.13 (s, 1H, bpy H2), 8.78 (d, J = 5 Hz, 1H, bpy H6), 8.67 (m, 2H, bpy H2',6'), 7.64 (m, 3H, bpy H3',5', bpy H5), 4.11 (t, J = 7 Hz, 2H, CO2CH2), 3.63 (t, J = 7 Hz, 2H, OCH2), 2.66 (t, J = 7 Hz, 4H, SCH2), 1.71 - 1.22 (m, ~36H. CH2); ES MS: m/z [M+Na]+ calcd 611.3317, found 611.3358.
Data for 194. White solid (91 mg, 31 %) Rf 0.35 (EA).
1H NMR (250 MHz, CDCl3): d 9.11 (s, 2H, bpy H2), 8.76 (d, J = 5Hz, 2H, bpy H6), 8.66 (m, 4H, bpy H2',6'), 7.22 (m, 6H, bpy H3',5', bpy H5), 4.09 (t, 4H, J = 7 Hz, CO2CH2), 2.64 (t, J = 7 Hz, 4H, SCH2), 1.63 (m, 4H, CH2), 1.47 - 1.11 (m, 16H, CH2); 13C NMR (62.9 MHz, CDCl3): d 165.8, 152.4, 151.4, 149.7, 147.5, 146.8, 125.8, 124.3, 122.7, 65.8, 39.1, 29.4, 29.4, 29.2, 29.1, 28.5, 28.2, 25.8; ES MS: m/z [M+H]+ calcd 771.3978, found 771.4014.
Thioacetic acid S-(11-bromo-undecyl) ester (195)
To a solution of potassium thioacetate (0.72 g, 6.4 mmol) in PEG 400 (5 mL) was added 1,11-dibromo-undecane (1.5 mL, 6.4 mmol). The solution was stirred under dry air at room temperature for 4.5 h. CHCl3 (50 mL) was added and the solution washed with water (50 mL, 30 mL), dried (MgSO4) and evaporated to a two phase oil. The portion of this mixture soluble in hexane/Et2O (20/1) was loaded on to a silica column which was eluted with this solvent to yield the desired product as a colourless oil (0.61 g, 31 %). Rf 0.27 (hexane/Et2O, 5/1).
1H NMR (500 MHz, CDCl3): d 3.37 (t, J = 7 Hz, 2H, CH2Br), 2.83 (t, J = 7 Hz, 2H, SCH2), 2.28 (s, 3H, COCH3), 1.81 (m, 2H, CH2), 1.54 (m, 2H, CH2), 1.38 (m, 2H, CH2), 1.37 - 1.24 (m, 12H, (CH2)6); 13C NMR (62.9 MHz, CDCl3): d 195.8, 33.8, 32.7, 30.5, 2 ´ 29.3, 2 ´ 29.0, 28.7, 28.6, 28.1; FAB MS: m/z [M+H]+ calcd 309.0871, found 309.0888; IR (CCl4): nmax 2928 (s), 2885 (s), 1694 (s), 1465 (m), 1353 (m), 1135 (m) cm–1.
2,8,12,18-Tetrahexyl-5,15-bis(3-hydroxyphenyl)-3,7,13,17-tetramethyl porphyrin (196)
2,8,12,18-Tetrahexyl-5-(3-hydroxyphenyl)-15-phenyl-3,7,13,17-tetramethyl porphyrin (197)
Prepared according to the standard procedure, except MeOH was used as solvent for the 3-hydroxybenzaldehyde. The three porphyrin products were separated chromatographically on silica gel eluted with hexane/EA (5/1).
Crystals of 196 and 197 for structure determination were grown by hexane vapour diffusion into EA solutions.
Data for 196: Rf 0.15 (hexane/EA, 5/1)
1H NMR (400 MHz, CDCl3 + DMSO-d6): d 10.08 (s, 2H, meso), 8.94 (s, 2H, ArOH), 7.39 (m, 6H, Ar), 7.14 (m, 2H, Ar), 3.84 (t, J = 8 Hz, 8H, hex H1), 2.47 (s, 12H, CH3), 2.04 (m, 8H, hex H2), 1.59 (m, 8H, hex H3), 1.37 (m, 8H, hex H4), 1.22 (m, 8H, hex H5), 0.77 (t, J = 7 Hz, 12H, hex H6), -2.64 (s, 2H, NH); 13C NMR (100.6 MHz, THF-d8): d 158.4, 145.9, 144.4, 143.8, 142.2, 136.9, 129.4, 125.3, 121.5, 119.0, 116.1, 97.3, 34.4, 33.0, 30.94, 27.4, 23.7, 14.8, 14.5; UV/vis (DCM): lmax 408, 506, 538, 572 nm; FAB MS: m/z [M+H]+ calcd 887.6203, found 887.6274; IR (CCl4): nmax 3604 (m), 2957 (s), 2928 (s), 2858 (m), 1593 (m), 1467 (m), 1444 (m), 1154 (m) cm–1; Anal. Calcd for C60H78O2N4: C 81.22, H 8.86, N 6.31. Found C 80.62, H 8.96, N 6.21.
Data for 197: Rf 0.43 (hexane/EA, 5/1)
1H NMR (400 MHz, CDCl3): d 10.22 (s, 2H, meso), 8.06 (d, J = 7 Hz, 2H, Ar), 7.75 (m, 3H, Ar), 7.59 (d, 1H, J = 7 Hz, Ar), 7.52 (t, J = 8 Hz, 1H, Ar), 7.29 (d, J = 1 Hz, 1H, Ar), 7.15 (m, 1H, Ar), 5.3 (br s, OH), 3.96 (t, J = 8 Hz, 8H, hex H1), 2.51 (s, 6H, CH3), 2.47 (s, 6H, CH3), 2.15 (m, 8H, hex H2), 1.72 (m, 8H, hex H3), 1.47 (m, 8H, hex H4), 1.29 (m, 8H, hex H5), 0.90 (t, J = 7 Hz, 12H, CH3), -2.41 (br, NH); 13C NMR (100.6 MHz, CDCl3): d 154.9, 145.1, 144.9, 143.6, 143.3, 142.3, 141.4, 136.3, 136.1, 133.0, 128.7, 128.2, 127.6, 120.3, 118.0, 117.2, 115.1, 97.0, 33.3, 32.0, 30.0, 26.8, 22.8, 14.6, 14.5, 14.1; FAB MS: m/z [M+H]+ calcd 871.6254, found 871.6318.
3-(11-Hydroxy-undecyloxy)-benzaldehyde (198)
Typical procedure. 3-Hydroxybenzaldehyde (5.00 g, 41 mmol), 11-bromoundecanol (6.85 g, 27 mmol) and Cs2CO3 (14.4 g, 44 mmol) were stirred in DMF (anhydrous, 36 mL) under N2 for 3 d at rt. Water (50 mL) was added to the dark suspension, which was extracted with Et2O (2 ´ 100 mL). The combined extracts were washed with brine (30 mL), dried (MgSO4) and evaporated to an orange oil which was redissolved in EtOH (several mL). Water (200 mL) was added, fo