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17th August 2010 @ 06:40
3. Step: Preparation of a strong achiral Brønstedt-acid, intended for determination and optimization of the reaction conditions for the acid-catalyzed Pictet-Spengler reaction [1,2]

See also:
1. Step: Preparation of the starting material -> see MW45-1
2. Step: Preparation of 1,1-Binaphthyl-2,2-disulfonate -> see MW45-2

Reaction Scheme


Table1


Hazard and Risk Assessment:
Reaction Class: 2
Hazards: C Corrosive, O Oxidizing agent
Risk rating: U = Unlikely
Note: Performic acid has a potential explosive hazard if it comes in contact with metals or their salts and is highly explosive in concentrated form!


MW45-3:
Start time: 7:00 PM 09/08/2010
End time: 10:10 PM 09/08/2010

Procedure: Modification of [2]
30% aq. H2O2 (700 µl) was added to formic acid (7.0 mL) and stirred for 1 h at room temperature. A solution of MW45-2 (50 mg, 109 µmol) in DCM (1 mL) was added dropwise to the formic acid solution and stirred for another 2 h.
Work-Up:
- quenched with 6 N HCl (5 mL), aqueous layer extracted with chloroform and ethyl acetate

-> 1H NMR: no or only traces of product
-> compound couldn’t extracted from the aqueous layer?


MW45-3a:
Repeated procedure of MW45-3:
- 30% aq. H2O2 (700 µl) was added to formic acid (7.0 mL) and stirred for 1 h at room temperature.
- added a solution of MW45-2 (50 mg, 109 µmol) in DCM (1 mL) dropwise and stirred for 2 h.
Work-Up:
- added water (3 mL) to the mixture: colorless solid precipitated
- the mixture was evaporated carefully under reduced pressure and the remaining water was removed by azeotropic distillation with toluene (3 times 5 mL).

-> 1H NMR: undefined aromatic signals
-> decomposition of the product due to a too long reaction time?


MW45-3b:
Start time: 4:10 PM 11/08/2010
End time: 5:40 PM 11/08/2010

Repeated procedure of MW45-3:
- 30% aq. H2O2 (700 µl) was added to formic acid (7.0 mL) and stirred for 1 h at room temperature.
- added a solution of MW45-2 (50 mg, 109 µmol) in DCM (1 mL) dropwise and stirred for 30 min.
Work-Up:
- added water (3 mL) to the mixture: colorless solid precipitated
- the mixture was evaporated carefully under reduced pressure and the remaining water was removed by azeotropic distillation with toluene (3 times 5 mL).

-> 1H NMR: product with impurities, signals match with the 1H NMR data of reference [1]
- large peak at 2.44 ppm (12 H) -> dimethyl ammonium salt as counter ion to the sulfonate?
-> use conditions for up-scaling reaction


MW45-3c:
Start time: 6:10 PM 13/08/2010
End time: 7:30 PM 13/08/2010

Up-scaled procedure of MW45-3:
- a solution of formic acid (20 mL) and 30 % aq. H2O2 (2.0 mL) was stirred for 1 h at room temperature
- added a solution of MW45-2 (434 mg, 109 µmol) in DCM (5 mL) was added dropwise and stirred for 20 min
- TLC (chloroform, 100%; stain: ceric ammonium molybdate) showed a complete consumption of the starting material after 15 min
- quenched with water (15 mL): pale yellow precipitate
- mixture was evaporated under reduced pressure and remaining water was removed by azeotropic distillation with toluene (3 times 5 mL).

-> yellow solid (448 mg)
-> 1H NMR showed a complete and selective conversion to the disulfonic acid / sulfonate, (1H NMR matches with date from reference [1]), but still one singulett peak at 2.55 pm (12H) – dimethyl ammonium something...

- small impurities of side products could removed by dissolving the residue in hot chloroform which obtained a pale yellow solid (407 mg), but still the deprotonated sulfonate with a ammonium counter ion
2. Work-up:
- using a Amberlite IR-120H ion exchange resin to protonate the sulfonate
- dissolved salt in MeOH/H2O (1:1) and passed it through a column of Amberlite IR-120H
- evaporate resulting solution and remove water by azeotropic distillation with toluene



References:
[1] “Pyridinium 1,1′-Binaphthyl-2,2′-disulfonates as Highly Effective Chiral Brønsted Acid−Base Combined Salt Catalysts for Enantioselective Mannich-Type Reaction”, M. Hatano, T. Maki, K. Moriyama, M. Arinobe and K. Ishihara, J. Am. Chem. Soc. 2008, 130, 16858–16860; DOI: 10.1021/ja806875c.

[2] “A Powerful Chiral Counteranion Motif for Asymmetric Catalysis”, P. García-García, F. Lay, P. García-García, C. Rabalakos, B. List, Angew. Chem. Int. Ed. 2009, 48, 4363 –4366; DOI: 10.1002/anie.200901768.

Procedure from the reference: [2]
(R)-3,3'-Bis[3,5-bis(trifluoromethyl)phenyl]-1,1'-binaphthyl-2,2'-disulfonic acid (3): A performic acid solution was prepared by mixing and stirring 30% H2O2 (7.01 mL, 69.6 mmol) and formic acid (70 mL) at room temperature for 1 h. To this solution S-thiocarbamte 13 (2.05 g, 2.32 mmol) in 35 mL dichloromethane was added dropwise. After stirring for 3 h, the solution was filtered over a pad of silica. The filtrate was concentrated in vacuo to furnish the crude product which was subjected to silica gel column chromatography using dichloromethane/methanol (20/1) as eluent.
The resulting Na-salt was dissolved in dichloromethane and washed with 6N HCl. Remaining water traces were removed by azeotropic distillation with toluene to yield 3 (1.57g, 81% yield).
Attached Files
Reaction Scheme
Table1