Synthesis of New Amphiphilic Dendrons Bearing Aliphatic Hydrocarbon Surface Sectors and a Monocarboxylic or Dicarboxylic Acid Focal Point (original) (raw)
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Supplementary Information Chem. Commun. 2012 D'Errico et al
All the reagents were obtained from commercial sources (Sigma-Aldrich) and were used without further purification. 1 H and 13 C-NMR spectra were acquired on a Varian Mercury Plus 400 MHz and on a Varian Unit Inova 700 MHz in CD 3 OD or CDCl 3 . Chemical shifts are reported in parts per million (δ) relative to the residual solvent signals: CD 2 HOD 3.31 and CHCl 3 7.27 for 1 H-NMR; CD 2 HOD 49.0 and CHCl 3 77.0 for 13 C-NMR. 1 H-NMR chemical shifts were assigned by 2D NMR experiments. The abbreviations s, bs, d, dd and m stand for singlet, broad singlet, doublet, doublet of doublets and multiplet, respectively. HPLC analyses and purifications were carried out on a Jasco UP-2075 Plus pump equipped with a Jasco UV-2075 Plus UV detector using a 4.60 x 150 mm LUNA (Phenomenex) silica column (particle size 5 µm) eluted with a linear gradient of MeOH in AcOEt (from 0 to 5% in 15 min, flow 1.0 mL min -1 , system A), with a linear gradient of AcOEt in n-hexane (from 0 to 100% in 30 min, flow 1.0 mL min -1 , system B) or using a 4.8 x 150 mm C-18 reverse-phase column (particle size 5 µm) eluted with a linear gradient of MeOH in H 2 O (from 0 to 100% in 30 min, flow 1.3 mL min -1 , system C). UV spectra were recorded on a Jasco V-530 UV spectrophotometer. High Resolution MS spectra were recorded on a Bruker APEX II FT-ICR mass spectrometer using electrospray ionization (ESI) technique in positive mode. Elemental analyses were performed on a Thermo Finnigan Flash EA 1112 CHN analyser. IR spectra were recorded on a Jasco FT-IR 430 spectrophotometer. Optical rotations were determined on a Jasco polarimeter using a 1 dm cell at 25 °C; concentrations are in g/100 mL. Preparative PLC chromatography was performed using F254 silica gel plates (0.5 mm thick, Merck). Analytical TLC analyses were performed using F254 silica gel plates (0.2 mm thick, Merck). TLC spots were detected under UV light (254 nm). For MTS assays the UV absorbance at 490 nm was read using a Beckman Anthos 96 well Microplate Reader.
Supporting Information Part I. Chemical Synthesis and Characterization General Procedures
All reagents were purchased from Sigma-Aldrich (St Louis, MO, USA) or Macrocyclics (Dallas, TX, USA) unless stated otherwise. Solvents were freshly distilled on appropriate driers and reactions run under an inert Argon atmosphere (CH 2 Cl 2 was distilled over P 2 O 5 , THF was distilled over sodium). All compounds apart from those containing Gd were fully characterized by 1 H (400 Hz) NMR, 13 C (400 Hz) (Bruker AMX-400 spectrometer) and the final products with Gd were characterized by mass spectrometry (EIMS and HRMS). Chemical shifts are expressed in δ ppm. All photophysical experiments were carried out using spectroscopic-grade solvents. Column chromatography was performed either over Silica Gel 60 (70-230 mesh) or neutral Alumina (Brockmann grade III, 50 mesh). UV-visible spectra were recorded on Varian Cary 50 Bio UV-visible spectrophotometer using CH 2 Cl 2 as solvent unless otherwise specified. Fluorescence spectra were recorded on a Varian Cary Eclipse fluorescence spectrophotometer with an excitation wavelength in the "Soret" band region between 410 and 425 nm.
Principles of organic chemistry
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General Details: All reactions were performed in oven-dried (120 o C) or flame-dried glass apparatus under dry N 2 or argon atmosphere. The solvents were dried and distilled from the indicated drying agents: CH 2 Cl 2 and CHCl 3 from P 2 O 5 ; THF and Et 2 O from sodium/benzophenone; toluene, benzene and hexanes from sodium; DMSO and DMF from CaH 2 . Sodium hydride (NaH) (55% in oil) and n-butyl lithium (1.6 M in hexanes) were obtained from Aldrich. Vanillin was obtained from Spectrochem (India). Tetrabutylammonium fluoride trihydrate and tetrabutylammonium chloride were obtained from Fluka. Compounds 5a,b, 6a,b, 7a-c, 11, [3] Pd(dba) 2 , [Pd(allyl)Cl] 2 , 4-acetamidoiodobenzene [6] and 1-iodo-2-methoxy-4-methylbenzene [6] were prepared following the literature procedures. Iodobenzene, 4iodoanisole, 1-iodonaphthalene, 4-iodotoluene were obtained from Lancaster. 1 H NMR and 13 C NMR spectra were recorded on a Bruker 200 MHz/500 MHz spectrometers. Spectra were referenced to residual chloroform (δ 7.25 ppm., 1 H; 77.00 ppm, 13 C). Chemical shifts are reported in ppm (δ); multiplicities are indicated by s (singlet), d (doublet), t (triplet), q (quartet), quint (pentet), m (multiplet) and br (broad). Coupling constants, J, are reported in Hertz. Mass spectra were recorded on a Fisons VG Quatro II mass spectrometer (EI 70 V; CI 30 V; ESI 3.5 KV). Infrared spectra (IR) were recorded on a Nicolet Impact 410 FT IR spectrophotometer in NaCl cells or in KBr discs. Peaks are reported in cm -1 . Melting points (m.p.) were determined on a Fischer John's melting point apparatus and are uncorrected. Analytical thin-layer chromatography was performed using home made silica gel plates (0.5 mm). 4-Benzyloxy-3-methoxybenzaldehyde (13): A mixture of vanillin (15 g, 98.68 mmol, 1 equiv), benzyl bromide (12.2 mL, 101.97 mmol, 1.03 equiv), tetrabutylammonium iodide (4.9 g, 13.16 mmol, 0.133 equiv) and anhydrous K 2 CO 3 (18.4 g, 131.24 mmol, 1.33 equiv) in DMF (132 mL) was stirred at 47 ºC under argon atmosphere. After 24 h, the reaction mixture was diluted with cold water and extracted with ether. The extract was washed with water and brine, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography followed by crystallization (hexane-EtOAc) to give product 13 [7] (32 g, 87%). M.p. 72-73 ºC; R f = 0.53 (hexane/EtOAc, 80:20). IR (CHCl 3 ): ν = 3019, 2939, 2835, 1683 (C=O), 1587, 1508 cm -1 . 1 H NMR (200 MHz, CDCl 3 ): δ = 3.95 (s, 3 H, MeOAr), 5.25 (s, 2 H, PhCH 2 O-), 6.98 (d, ppm. 4-Benzyloxy-3-methoxybenzoic acid (14) and 4-benzyloxy-3-methoxybenzylalcohol (15): A solution of aldehyde 13 (30 g, 123.97 mmol, 1 equiv) and KOH (21 g, 374.35 mmol, 3 equiv) in methanol (33 mL) was heated with stirring at 90 ºC for 3 hrs. The reaction was cooled to room temperature and the resulting cake was dissolved in KOH (2 M, 90 mL). The reaction mixture was extracted with 1/1 benzene-ether and the combined organic extract was washed with dilute KOH solution (0.5 M), dried over anhydrous K 2 CO 3 and evaporated. The residue was crystallized (benzene-petroleum ether) to give alcohol 15 [8] (13.6 g, 45%). The combined aqueous portion was cooled in ice-water bath, acidified with HCl and extracted with ethyl acetate. The combined organic extract was washed with water, dried (MgSO 4 ) and evaporated. The residue was crystallized (EtOAc) to give the acid 14 [9] (14 g, 44%). Data for 4-benyloxy-3-methoxybenzoic acid (14): M.p. 172-174 ºC. R f = 0.2 (hexane/EtOAc, 50:50). 1 H NMR (200 MHz, CDCl 3 ): δ = 3.95 (s, 3 H, MeOAr), 5.24 (s, 2 H, PhCH 2 O-), 6.92 (d,
Reactive trityl derivatives: stabilised carbocation mass-tags for life sciences applications
Organic & Biomolecular Chemistry, 2008
Instrumentation. 500 MHz 1 H and 125.7 MHz 13 C NMR spectra were recorded on a Bruker DRX-500 spectrometer and referenced to CDCl 3 (7.25 ppm) and DMSO-d 6 (2.50 ppm). 1 H-13 C gradient-selected HMQC and HMBC spectra were obtained by using 2048 (t 2 )×256 (t 1 ) complex point data sets, zero filled to 2048 (F 2 )×1024 (F 1 ) points. The spectral widths were 13 ppm and 200 ppm for 1 H and 13 C dimensions, respectively. HMBC spectra were measured with 50 ms delay for evolution of long-range couplings. (MA)LDI-TOF mass spectra were obtained using a Voyager Elite Biospectrometry Research Station (PerSeptive Biosystems, Vestec Mass Spectrometry Products) in a positive ion mode. EI-TOF HRMS and ESI-TOF HRMS spectra in positive ion mode were obtained using Micromass LCT reflection TOF mass spectrometer. Analytical thin-layer chromatography was performed on the Kieselgel 60 F 254 precoated aluminium plates (Merck), spots were visualised under UV light (254 nm). Column chromatography was performed on silica gel (Merck Kieselgel 60 0.040-0.063 mm). Reagents and solvents. Reagents obtained from commercial suppliers were used as received. 4-Hydroxy-4′-methoxybenzophenone (3), [1] Pd(PPh 3 ) 4 , tert-butyl 6-bromohexanoate, were prepared as described. Solvents were mainly HPLC grade and used without further purification unless otherwise noted. DCM was always used freshly distilled over CaH 2 . THF was distilled over powdered LiAlH 4 or over sodium benzophenone ketyl and stored over 4Å molecular sieves under nitrogen. DMF was freshly distilled under reduced pressure. OH O O O O O Cl(CH 2 ) 3 CO 2 Bu t MeONa / HMPA 75%