All Notebooks | Help | Support | About
Archives
Sections
Mnr
Sc
Tools
Show/Hide Keys
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
3rd August 2010 @ 09:28
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

Reaction Scheme


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).
Attached Files
2nd August 2010 @ 09:14
Intermediate 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]

Reaction Scheme MW45-1


Table1


Hazard and Risk Assessment:
Reaction Class: 2
Hazards: T toxic, X Irritant, C Corrosive, F Flammable
Risk rating: U = Unlikely

Start time: 4:30 AM 02/08/2010
End time: 6:30 PM 02/08/2010

Procedure: [1]
To an ice cooled solution of (+/-)-1,1’-bi(2-naphthol) (1.00g, 3.49 mmol) in dry DMF (10 mL) under argon was added sodium hydride (350 mg, 8.73 mmol, 2.5 eq.; 60% oil dispersion), warmed to room temperature and stirred for 10 min. The resulting yellow solid was slightly heated to obtain a yellow dispersion. To the dispersion N,N-dimethylthiocarbamoyl chloride (950 mg, 7.68 mmol, 2.2 eq.) was added at room temperature and heated to 85°C for 1.5 h.
Work-up:
The yellow-brown mixture was cooled to room temperature and poured into 1% aqueous KOH solution (30 mL). The pale brown solid was filtered off, washed with water and dissolved in DCM. The organic layer was separated from the remaining water, washed with brine and dried over sodium sulfate. After evaporation of the solvent a pale yellow solid was obtained.

Crude product:
1.83 g (3.98 mmol, 114%) pale yellow solid MW45-1,
1H/13C NMR showed a good purity of the product, but remaining DMF
Data: 1H NMR MW45-1 Data: 13C NMR MW45-1

- dissolved product in chloroform and washed 3 times with brine, dried over sodium sulfate and concentrated

Result:
1.50 g (3.26 mmol, 93%) pale yellow solid MW45-1,
1H NMR: DMF could be removed, minor impurities for hexane/mineral oil

-> no further purification for the following step MW45-2


Analytical data: [1]
1H NMR (CDCl3, 200 MHz): δ = 2.51 (s, 6H), 3.07 (s, 6H), 7.25-7.32 (m, 2H), 7.40-7.47 (m, 4H), 7.61 (d, J = 8.8 Hz, 2H), 7.87-8.01 (m, 4H).
Data: 1H NMR MW45-1a
13C NMR (CDCl3, 500 MHz): δ = 38.2 (2C), 42.9 (2C), 123.8 (2C), 124.1 (2C), 125.8 (2C), 126.5 (2C), 126.9 (2C), 127.9 (2C), 128.4 (2C), 131.6 (2C), 133.4 (2C), 149.6 (2C), 186.3 (2C).
Data: 13C NMR MW45-1
IR (neat): nu = 2924 cm-1, 2855, 1665, 1524, 1502, 1385, 1282, 1207, 1129, 1091, 812, 752.
Data: IR MW45-1a
C26H24N2O2S2 (460.6).


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: [1]
(R)-1,1’-Binaphthalene-2,2’-diyl-O,O’-bis(N,N-dimethylthiocarbamate)
(3):1,2 An ice cooled solution of (R)-BINOL (14.3 g, 50.0 mmol) in 100 mL of distilled DMF under N2 was treated under vigorously stirring with NaH (4.4 g, 110 mmol; 60% oil dispersion). To the resulting yellow solution was added N,N-dimethylthiocarbamoyl chloride (13.6 g, 110 mmol) at 0 °C, and the solution was warmed at 85 °C for 1 h by monitoring with the TLC. Then, the reaction mixture was cooled to room temperature and poured into 1% aqueous KOH (300 mL). The colorless precipitate was filtered, washed thoroughly with water, and dissolved in CH2Cl2.
The CH2Cl2 solution was dried over MgSO4 and evaporated to obtain a colorless solid that was recrystallized from CHCl3/hexane (20.2 g, 88% yield). 1H NMR (300 MHz, CDCl3) δ 2.52 (s, 6H), 3.08 (s, 6H), 7.30 (ddd, J = 8.4, 7.1, 0.9 Hz, 2H), 7.42-7.48 (m, 4H), 7.62 (d, J = 8.7 Hz, 2H), 7.91 (d, J = 8.7 Hz, 2H), 7.97 (d, J = 8.7 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 37.9 (2C), 42.6 (2C), 123.6 (2C), 123.8 (2C), 125.6 (2C), 126.2 (2C), 126.6 (2C), 127.6 (2C), 128.2 (2C), 131.3 (2C), 133.1 (2C), 149.3 (2C), 186.0 (2C). IR(KBr) 2934, 1537, 1394, 1286, 1213, 1136, 1119, 812, 751 cm–1. [α]D
22.8 = +156.1 (c 1.0, CHCl3). HRMS(FAB+) calcd for 26H24N2O2S2 [M]+ 460.1279, found 460.1276.

See following experiments:
Preparation of 1,1’-Binaphthalene-2,2’-diyl-S,S’-bis(N,N’-dimethylthiocarbamate) (MW45-2)
Preparation of 1,1’-Binaphthalene-2,2’-disulfonic acid (MW45-3)
Attached Files