Post synthetic exchange enables orthogonal click chemistry in a metal organic framework

Post synthetic linker exchange can be combined with Cu-catalyzed alkyne/azide click chemistry to enable orthogonal modification of known metal organic frameworks.

Electronic Supplementary Material (ESI) for Dalton Transactions. This journal is © The Royal Society of Chemistry 2018

General details
All purchased chemicals were used without further purification except where otherwise stated.
Dimethylformamide used for synthesizing UiO-67 was pre-dried over 4 Å molecular sieves. Xray powder diffraction patterns were collected using a Siemens D5000 utilizing a monochromatic Cu Kα radiation source at 40 kV, 40 mA for Cu Kα, (λ = 1.5406 Å) with a scan speed of 0.10 sec/step from 5 to 40º at a step size of 0.02º. NMR spectra were obtained using a JEOL Eclipse+ 400 MHz spectrometer and chemical shifts reported vs. the residual NMR solvent peak. 1 Infrared spectra (IR) were collected on a PerkinElmer ATR-FT-IR spectrometer.
Scanning electron microscopy (SEM) was performed on a Zeiss 1550 with AZtec EDS equipped with InLens, SEII, and BSD detectors. The measurements were performed at 3 kV at working distances of 3.2 to 4.0 mm. The samples were sputtered prior to the measurements with a Polaron Sputter Coater (Au/Pd) for 40 seconds.
UiO-67 was synthesized according to known procedures. 2 In brief, 1 eq of [1,1'-biphenyl]-4,4'dicarboxylic acid, 1 eq of ZrCl4 and 33 eq of acetic acid were suspended in dry DMF (4 mL for 0.11 mmol ligand), placed in screw cap vials and heated at 120 °C for 24 hours. After cooling to room temperature, the clear supernatant was removed and the MOF crystals resuspended in fresh MeOH. The solvent was renewed after 24 hours with fresh solvent and this washing repeated three times, with the final MOF product stored in fresh MeOH.

Synthesis of methyl 3-bromo-4-iodobenzoate (1):
1 g 3-bromo-4-iodobenzoic acid (1 eq) was suspended in 30 mL of dichloromethane. 889 µl (4 eq) of SOCl2 was added dropwise and the reaction mixture stirred for 1 hour at room temperature. The mixture was cooled to 0 °C before 10 ml methanol was slowly added. After the addition was finished the reaction was warmed to room temperature and stirred overnight.
The volatile components were removed and the residue redissolved in dichloromethane and water, extracted with dichloromethane, dried over MgSO4 and the solvent removed under reduced pressure. 1.2 g of the product was isolated as brown solid (97% yield). 1

Synthesis of dimethyl 2-bromo-[1,1'-biphenyl]-4,4'-dicarboxylate (3):
(4-(methoxycarbonyl)phenyl)boronic acid (400 mg, 1 eq) and 1 (211 mg, 1 eq) were dissolved in 10 ml DMF. Na2CO3 (248 mg, 2 eq) and 2 ml of water were added and the resulting mixture was degassed by bubbling nitrogen through the solution for 10 minutes. Palladiumtetrakis(triphenylphosphine) (5 mol%) was added and the reaction mixture was heated at 80 °C for 6 hours. After cooling to room temperature, the mixture was diluted with water and extracted with dichloromethane. After removing the solvent under reduced pressure the crude product was purified by column chromatography
After cooling to room temperature the reaction was quenched with NH4Cl solution and extracted 3 times with dichloromethane. The organic fractions were combined and the solvent removed under reduced pressure. The crude product was purified by Kugelrohr distillation. At 80 °C triphenylphosphine oxide was removed before the temperature was increased to 150 °C to give the pure product as a waxy solid. 432 mg; 82% yield.

Synthesis of dimethyl 2-ethynyl-[1,1'-biphenyl]-4,4'-dicarboxylate ester (5):
4 (200 mg, 1 eq) was dissolved in dichloromethane and 5 eq of TBAF (1M, 500 µL, 5 eq) was added. The mixture was stirred for 1 hour at room temperature before the reaction was quenched with water and extracted with dichloromethane. The combined organic fractions were dried over MgSO4 and the solvent was removed under reduced pressure. The crude material was purified by flash chromatography and gave the pure product as off-white solid in 103 mg (64% yield).
The reaction was stirred for 2 hours before the mixture was acidified with HCl to a pH of 1.
Ethyl acetate was used for extraction. The combined organic fractions were washed with brine and dried over MgSO4 prior to the removal of solvent under reduced pressure. The product was obtained as light brown solid in above 90% yield.

Synthesis of dimethyl 2-nitro-[1,1'-biphenyl]-4,4'-dicarboxylate (8):
Method adapted from the literature. 3 Dimethyl-[1,1'-biphenyl]-4,4'-dicarboxylate (1.5 g, 1 eq) was dissolved in 20 mL of concentrated H2SO4 at room temperature before being cooled to -30 °C. 0.9 eq of 1/2 concentrated nitric acid in 2 mL H2SO4 was added drop wise under vigorous stirring at below -20°C. The mixture was kept at this temperature for two hours before the reaction mixture was poured onto crushed ice. Upon melting of the ice the precipitate was separated by filtration and washed thoroughly with water to remove residue acid. The crude product was purified by recrystallization from isopropanol to give 8 as white solid in 76% yield.
The combined organic phases were dried over MgSO4 before the solvent was removed under reduced pressure to give the product as yellow solid in quantitative yield.
The combined organic fractions were washed with brine and dried over MgSO4 before the solvent was carefully removed under reduced pressure without heating. The volatile product was used without further purification. Yield 295 mg; 74% as clear oil.

Synthesis of 1-ethynyl-4-(trifluoromethyl)benzene (15)
2 g Iodo-4-(trifluoromethyl)benzene (1 eq), bis(triphenylphosphine)palladium dichloride (340 mg, 4 mol%) and CuI (56 mg, 4 mol%) were suspended in 10 mL of distilled THF and 10 mL of Et3N. The mixture was degassed for 10 minutes by bubbling nitrogen through the solution. After this 1.25 mL TMS-acetylene was added, the reaction vessel was sealed and heated to 40 °C for 4 hours. After cooling to room temperature the reaction was quenched with NH4Cl and extracted with pentane. After removing the solvent under reduced pressure the product was purified by column chromatography using pentane as solvent to yield the product as off-white liquid in 69% yield (874 mg). Due to volatility the product was stored as TMS protected version and deprotected prior to use: 1 eq of trimethyl((4-(trifluoromethyl)phenyl)ethynyl)silane was dissolved in dichloromethane and 2 eq of TBAF (1M in DCM) was added. The mixture was stirred for 1 hour, quenched with water, dried over MgSO4 and the solvent was carefully removed with an air flow.         Powder X-ray diffraction patterns Figure S11. Powder X-ray diffraction patterns comparing native UiO-67 with MOF-N3/C≡C before (blue) and after (red) the two step click reactions.