Pictet-Spengler route to Praziquantel

 

2. step for the preparation of 1,1-Binaphthyl-2,2-disulfonate – a strong achiral Brønstedt-acid, intended for determination and optimization of the reaction conditions for the acid-catalyzed Pictet-Spengler reaction [1,2]

1. step: preparation of the starting material -> see MW45-1



Hazard and Risk Assessment:
Reaction Class: 2
Hazards: T toxic
Risk rating: U = Unlikely

Start time: 1:00 PM 03/08/2010
End time: 2:20 PM 03/08/2010

Procedure: [2]
MW45-1 (500 mg, 1.09 mmol) was placed in a roundbottom flask and heated in a heating mantle to 250°C for 80 min. The dark brown solid was dissolved in chloroform and purified by column chromatography (silica gel, CHCl3; 100%).

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.

See following experiment:

Preparation of 1,1’-Binaphthalene-2,2’-disulfonic acid (MW45-3)

Procedure from the reference:

[2]
(R)-3,3'-Bis[3,5-bis(trifluoromethyl)phenyl]-1,1'-binaphthyl-2,2'-diyl-S,S'-bis(N,N-dimethylthiocarbamate) (13):
O-Thiocarbamate 12 (2.31 g, 2.61 mmol) was placed into a dram glass vial under argon and heated in a metal block to 250 °C for 80
min. The resulting crude product was purified by column chromatography using hexanes/ethyl acetate (95/5) as eluent to afford 13 (2.19 g, 95% yield).