Catalyst Screening & TLC-MS for Reaction Analysis

Sarah Trice, Thorsten vom Stein, Michael Schulz

Introduction

Catalyst screening is an important prerequisite in organic synthesis. KitAlysis™ High-Throughput Screening Kits showcase the most widely used catalytic methods of synthetic chemists, translated into an off-the-shelf screening system to quickly and efficiently identify or optimize suitable catalytic reaction conditions.

To evaluate the screening an analysis tool is needed. Thin layer chromatography (TLC) allows for a fast and cost-effective determination of the reaction progress by parallel analysis of the samples on one plate. This setup perfectly fits to the parallel synthesis utilizing KitAlysis™.

This application note displays the use of the KitAlysis™ High-Throughput Buchwald-Hartwig Amination Reaction Screening Kit for the optimization of the coupling of aryl bromide and diphenylamine combined with an evaluation of the result with TLC-MS analysis.

Figure 1. Schematic reaction showing the coupling of aryl bromide (1) and diphenylamine (2) to form biphenyl-4-yl-di-p-tolyl-amine (3), where the product has a molecular weight of 349.468 g/Mol.

Results and Discussion

The two reactants, aryl bromide and diphenylamine, were applied in addition to the samples. The samples were clearly visible under UV-light, therefore no derivatization was necessary. Figures 2a, 2b and 2c show the developed plate under white light, at 254 nm and at 366 nm.

Good reaction progress was observed in tracks 1 – 5 and 8 – 12. Byproduct formation somewhat different in the lower Rf value region as well as amine educt amount (Rf 0.19). Significant concentrations of educts were observed in tracks 6 and 7 (MorDalPhos Pd G3, BINAP Pd G3).

Track	Samples / Catalysts KITALYSIS-CN	Concentration	Application volume	Rf of product and educts
1	BrettPhos Pd G3	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
2	CPhos Pd G3	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
3	DavePhos Pd G3	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
4	P(tBu3) Pd G2	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
5	J009 Pd G3	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
6	MorDalPhos Pd G3	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
7	BINAP Pd G3	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
8	RuPhos Pd G2	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
9	SPhos Pd G2	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
10	tBuXPhos Pd G3	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
11	XantPhos Pd G3	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
12	XPhos Pd G3	KitAlysis™ sample filled up with 1 ml THF	2.0 µL	0.50
13	amine educt	1 mg/mL	1.0 µL	0.19
14	Ar-Br educt	1 mg/mL	1.0 µL	0.77

Figure 2a. Developed plate under white light

Figure 2b. Developed plate at 254 nm

Figure 2c. Developed plate at 366 nm

Confirmation of reaction product by mass spectrometry: Formation of ACN adduct via radical ionization

Figure 3. Mass spectrum (ESI+) of product [M+ACN]

Biphenyl-4-yl-di-p-tolyl-amine (M=349.568 g/Mol)

Application Data

Chromatography	Plate	HPTLC Silica gel 60 F254 MS-grade
	Sample preparation	Fill up the KiTAlysis™ samples with 1mL tetrahydrofuran (THF) Educts: Dissolve 1 mg each in 1 mL THF
	Sample application	ATS 4 sample applicator (Camag), 6 mm bandwise
	Application volume	1.0 µl track 13-14 / 2.0 µL track 1-12
	Mobile phase	n-Heptane / dichloromethane 6/1 (v/v) + 0.1% trifluoroacetic acid
	Migration distance	5 cm
	Migration time	10-11 min
Extraction	Extraction equipment	Plate Express (Advion)
	Extraction solvent	Acetonitrile / water 95/5 (v/v) + 0.1 % formic acid
	Extraction flow	0.2 mL/min
Detection	Documentation equipment	TLC Visualizer (Camag)
	Wavelength	scan at white light, 254 nm, 366 nm
	Staining	-
	MS equipment	Single quadrupole mass spectrometer Expression CMS (Advion)
	MS detection	ESI(+) mode (m/z 50 - 1200)

Materials

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