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20th January 2011 @ 06:30
Racemization experiments of enantioenrichend S-(+)-PZQamine, obtained from Multigram-scale racemic resolution of praziquanamine, with (-)-Dibenzoyl-L-tartaric acid (MW49-13), with Raney nickel

Scheme MW50-6.png


See also:
Racemization of S-(+)-PZQamine with Pd/C (MW50-1 to MW50-3)
Racemization of S-(+)-PZQamine with Pd/C (MW50-4)
Racemization of S-(+)-PZQamine with Pd/BaSO4 (MW50-5)
Thiyl radical-mediated racemization of S-(+)-PZQamine (MW50-8)

Hazard and Risk Assessment:
HRAF MW50.pdf


Start time: 6:00 PM 20/01/2011
End time: 24/01/2011

To a solution of S-(+)-PZQamine (20 mg, 98.9 µmol, MW: 202.3 g/mol) in ethanol (3 mL) was added Raney nickel (291 µg, 4.95 µmol, 0.05 eq.; 2.9 mg suspension of Raney nickel (Suspension in water ~0.1 g/mL), M.W. (Ni) 58.7 g/mol) and heated to 70°C for XX h.

Note:
Stirring bar can't be used, because the paramagnetic nickel adhere to the magnet

MW50-6:
under air -> almost no racemization after 1 day

MW50-7:
under hydrogen atmosphere (1 bar)
[α]D20 = +85° (c=1, DCM) -> slow racemization after 4 days



[1] "Heterogeneous Raney Nickel and Cobalt Catalysts for Racemization and Dynamic Kinetic Resolution of Amines", A. Parvulescu, P. Jacobs, D. De Vos, Adv. Synth. Catal. 2008, 350, 113-121.(DOI: 10.1002/adsc.200700336)
Attached Files
20th January 2011 @ 05:38
Racemization experiments of enantioenrichend S-(+)-PZQamine, obtained from Multigram-scale racemic resolution of praziquanamine, with (-)-Dibenzoyl-L-tartaric acid (MW49-13), with Pd supported on barium sulfate

Scheme MW50-5.png


See also:
Racemization of S-(+)-PZQamine with Pd/C (MW50-1 to MW50-3)
Racemization of S-(+)-PZQamine with Pd/C (MW50-4)
Racemization of S-(+)-PZQamine with Raney Nickel (MW50-6, MW50-7)
Thiyl radical-mediated racemization of S-(+)-PZQamine (MW50-8)

Hazard and Risk Assessment:
HRAF MW50.pdf


Start time: 5:00 PM 20/01/2011
End time: 5:00 PM 24/01/2011

To a solution of S-(+)-PZQamine (20 mg, 98.9 µmol, MW: 202.3 g/mol) in toluene (5 mL) was added Pd/BaSO4 (5.27 mg, 4.95 µmol, 0.05 eq.; 10% Pd on BaSO4, M.W. (Pd) 106.4 g/mol) and heated to 70°C for 4 days.

[α]D20 = -24.8° (c=1, DCM) -> racemization

Data: 1H NMR MW50-5.pdf: no more PZQamine - sompletely decomposed

[1] "Efficient dynamic kinetic resolution of secondary amines with Pd on alkaline earth salts and a lipase", Andrei Parvulescu, Dirk De Vos and P. Jacobs, Chem. Commun. 2005, 5307-5309. (DOI: 10.1039/B509747A)
Attached Files
18th January 2011 @ 04:47
Varying conditions of the previous experiment Racemization of S-(+)-PZQamine with Pd/C (MW50-1 to MW50-3)

Racemization experiments of enantioenrichend S-(+)-PZQamine with Pd/C obtained from Multigram-scale racemic resolution of praziquanamine with (-)-Dibenzoyl-L-tartaric acid (MW49-13)

Scheme MW50-1.png


See also:
Racemization of S-(+)-PZQamine with Pd/C (MW50-1 to MW50-3)
Racemization of S-(+)-PZQamine with Pd/BaSO4 (MW50-5)
Racemization of S-(+)-PZQamine with Raney Nickel (MW50-6, MW50-7)
Thiyl radical-mediated racemization of S-(+)-PZQamine (MW50-8)

Hazard and Risk Assessment:
HRAF MW50.pdf


Start time: 4:20 PM 18/01/2011
End time: 4:50 PM 19/01/2011

To a solution of S-(+)-PZQamine (50 mg, 248 µmol, MW: 202.3 g/mol) in toluene (5 mL) was added Pd/C (13.1 mg, 12.4 µmol, 0.05 eq.; 10% Pd on charcoal, M.W. (Pd) 106.4 g/mol) and heated to 90°C for 24 h.
The catalyst was filtered off by a filter paper and the solvent was evaporated.

Yield: 47 mg of a yellow solid reisolated
[α]D20 = +146° (c=1, DCM)

Starting material S-(+)-PZQamine
[α]D20 = +170° (c=1, DCM)

Results:
- slow racemization of S-(+)-PZQamine even with 5% Pd/C

-> Pd/C is not a suitable catalyst for the racemization of PZQamine
-> screening other catalysts like Pd/BaSO4, Pd/CaCO3, Raney nickel



References:
[1] "Fast racemization and dynamic kinetic resolution of primary benzyl amines", Y. Kim, J. Park and M.-J. Kim, Tetrahedron Letters 2010,51, 42, 5581-5584, (http://dx.doi.org/10.1016/j.tetlet.2010.08.050)
[2] "Lipase/Palladium-Catalyzed Asymmetric Transformations of Ketoximes to Optically Active Amines", Y. K. Choi, M. J. Kim, Y. Ahn, and M.-J. Kim, Org. Lett. 2001, 3, 25, 4099–4101;
DOI: 10.1021/ol0168622
17th January 2011 @ 03:59
Racemization experiments of enantioenrichend S-(+)-PZQamine with Pd/C obtained from Multigram-scale racemic resolution of praziquanamine with (-)-Dibenzoyl-L-tartaric acid (MW49-13)

Scheme MW50-1.png


See also:
Racemization of S-(+)-PZQamine with Pd/C (MW50-4)
Racemization of S-(+)-PZQamine with Pd/BaSO4 (MW50-5)
Racemization of S-(+)-PZQamine with Raney Nickel (MW50-6, MW50-7)
Thiyl radical-mediated racemization of S-(+)-PZQamine (MW50-8)

Hazard and Risk Assessment:
HRAF MW50.pdf


Start time: 3:50 PM 17/01/2011
End time: 1:40 PM 18/01/2011

To a solution of S-(+)-PZQamine (50 mg, 248 µmol, MW: 202.3 g/mol) in toluene (5 mL) was added Pd/C (for 1% Pd: 2.62 mg, 2.48 µmol; for 5% Pd: 13.1 mg, 12.4 µmol; 10% Pd on charcoal, M.W. (Pd) 106.4 g/mol) and heated to 70°C for 3 / 22 h.
The catalyst was filtered off by a filter paper and the solvent was evaporated.

Notes:
- almost complete amount of starting material was reisolated
- color of the starting material turned from pale yellow to yellow

Starting material S-(+)-PZQamine
[α]D20 = +170° (c=1, DCM)

MW50-1
1% Pd, 3 h
[α]D20 = +156° (c=1, DCM)

MW50-2
5% Pd, 3 h
[α]D20 = +131° (c=1, DCM)
Data: 1H NMR MW50-2.pdf
-> no decomposition / side reaction of the starting material

MW50-3
1% Pd, 2 h
[α]D20 = +152° (c=1, DCM)


Results:
- slow racemization of S-(+)-PZQamine with 1% Pd/C under the conditions stated above
-> increase of temperature and catalyst loading (5% Pd)

References:
[1] "Fast racemization and dynamic kinetic resolution of primary benzyl amines", Y. Kim, J. Park and M.-J. Kim, Tetrahedron Letters 2010,51, 42, 5581-5584, (http://dx.doi.org/10.1016/j.tetlet.2010.08.050)

[2] "Lipase/Palladium-Catalyzed Asymmetric Transformations of Ketoximes to Optically Active Amines", Y. K. Choi, M. J. Kim, Y. Ahn, and M.-J. Kim, Org. Lett. 2001, 3, 25, 4099–4101;
DOI: 10.1021/ol0168622
Attached Files