Ionic liquids vs . microporous solids as reusable reaction media for the catalytic C-H functionalization of indole with alcohols

Ionic liquids vs. microporous solids as reusable reaction media for the catalytic C-H functionalization of indole with alcohols Francisco G. Cirujano*, Maxime Stalpaert and Dirk E. De Vos* Centre for Surface Chemistry and Catalysis, Department of Microbial and Molecular Systems (M2S), KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium * corresponding authors: francisco.garcia@kuleuven.be; dirk.devos@kuleuven.be


Synthesis of non-commercially available catalysts
HBr@Bu 4 PBr: The synthesis of HBr@Bu 4 PBr was adapted from the method reported. 1riefly, 10 μl HBr (48%) were added to 1 g of solid Bu 4 PBr.The partially melted HBr@Bu 4 PBr white solid was stirred at room temperature for 0.5 h and used as reaction media and catalyst.The same recipe was extended to other ionic liquids (see Table S2).The samples of ZnCl 2 @Bu 4 PBr, FeCl 3 @Bu 4 PBr, CrCl 3 @Bu 4 PBr, AlCl 3 @Bu 4 PBr and ZrCl 4 @Bu 4 PBr were prepared using the corresponding metal chlorides (1 wt.% respect to the amount of ionic liquid) instead of HBr and keeping the rest of the method the same.The (Zn)BDC, (Cr)BDC and (Zr)UiO-66 metal-organic frameworks were prepared following reported methods, [2][3][4] in order to establish comparisons with the rest of the transition metal containing catalysts.

Reaction conditions
The reactions were performed as follows: 1 mmol (117 mg) of indole, 1.2 mmol of alcohol (182 mg for 4-methoxy-α-methylbenzyl alcohol, 254 mg for benzoin, 168 mg for (3,4dimethoxy)benzyl alcohol) and n-tetradecane (198 mg, 1 mmol) as the internal standard for the analysis with gas chromatography (GC) coupled with a flame ion detector (FID), were added to a glass vessel containing 500 mg of MX n @Bu 4 PBr (containing 1 %wt. of MX n = HBr, ZnCl 2 , FeCl 3 , AlCl 3 , CrCl 3 , ZrCl 4 ) in the case of ionic liquids or 40 mg of porous solid.The vials were closed and transferred into an aluminum heating block preheated to 50 ⁰C or 70 ⁰C in order to obtain compounds 1, 3 (50 ⁰C) or 4 (70 ⁰C).The mixture was stirred (400 rpm) at this temperature and sample aliquots were taken at different reaction times.In the case of the MX n @Bu 4 PBr ionic liquid (solid at room temperature), its viscosity decreases upon heating above room temperature, obtaining a homogeneous reaction mixture (see Figure S6a).The reaction products were recovered by extraction with mesitylene (1,3,5-trimethylbenzene) and analyzed by GC/MS using a GC Shimadzu 2014 GC instrument equipped with a FID detector and a CP-Sil 5 CB column.Mass Spectra were obtained with a GC/MS Agilent 6890 gas chromatograph, equipped with a HP-5MS column, coupled to a 5973 MSD mass spectrometer with electron impact ionization.The ionic liquid was resused after washing (50 ⁰C, 5 min, 400 rpm) three times with mesitylene, separated by centrifugation and dried in a stream of nitrogen at room temperature.For the porous solids, the solvent-free suspension was stirred (300 rpm) at the desired temperature and sample aliquots were taken from the supernatant upon centrifugation (3000 rpm, 10 min) at different reaction times.The supernatant solution was analyzed with GC-FID.The solid was separated by centrifugation, washed with mesitylene, ethanol and subsequently dried in a stream of nitrogen at room temperature for a subsequent reuses.

Figure S3
. Batch reaction between indole and alcohols using ionic liquid or microporous solid to obtain indole derivatives.To have an idea of the costs, the price values of the compounds were obtained from sigma-aldrich and zeolyst international.HBr@Oct 4 PBr

Figure S1 N 2
Figure S1N 2 physisorption isotherm of the HY CBV720 commercial zeolite heterogeneous catalyst, performed at 77 K on a Micromeritics TriStar instrument.Before measurement, the sample was dried overnight at 573 K.

Figure S9 .
Figure S9.Reaction rate (r 0 ) for the synthesis of 1 from indole and 4-methoxy-α-methylbenzyl alcohol with (a) HY zeolites with increased Si/Al ratio (increased Lewis acid strength & hydrophobicity) and (b) Bu 4 PBr containing increased amounts of HBr.

Table S2 .
Conversion of indole and selectivity to 1 in different HBr @ Ionic liquids (1%wt.
P Br