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Racemization of PZQ and PZQamine
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1st March 2011 @ 08:22
Racemization experiments on (R)-(-)-PZQ (MW48-5)

Scheme MW55.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)

Hazard and Risk Assessment:
HRAF MW50.pdf


Start time: 7:30 PM 1/03/2011
End time: 10:30 PM 4/03/2011

MW55-1 (catalyst Pd/C)
To a solution of (R)-(-)-PZQ (24.5 mg, 78.4 µmol, MW: 312.4 g/mol) in toluene (2 mL) was added Pd/C (8.3 mg, 7.84 µmol, 0.1 eq.; 10% Pd on charcoal, M.W. (Pd) 106.4 g/mol) and heated to 70°C for 3 d.
[α]D20 = -129° (c=1, EtOH) [1]
- filtered and evaporated: yield 24 mg (98%)
Chiral HPLC [2] Data: MW55-1.jpg: (R)-PZQ / (S)-PZQ = 92:8
-> no /minor racemization

MW55-2 (catalyst Pd/BaSO4)
To a solution of (R)-(-)-PZQ (20.0 mg, 64.0 µmol) in toluene (2 mL) was added Pd/BaSO4 (6.8 mg, 6.4 µmol, 0.1 eq.; 10% Pd on BaSO4, M.W. (Pd) 106.4 g/mol) and heated to 70°C for 3 d.
- filtered and evaporated: yield 21 mg (105%)
[α]D20 = -122° (c=1, EtOH) [1]
Chiral HPLC [2] Data: MW55-2.jpg: (R)-PZQ / (S)-PZQ = 93:7
-> no /minor racemization

MW55-3 (catalyst Raney nickel)
To a solution of (R)-(-)-PZQ (20.7 mg, 66.3 µmol) in ethanol (2 mL) was added Raney nickel (389 µg, 66.3 µmol, 0.1 eq.; 3.9 mL suspension of Raney nickel (Suspension in water ~0.1 g/mL), M.W. (Ni) 58.7 g/mol) and heated to 70°C for 3 d.
- filtered and evaporated: yield 18 mg (87%)
[α]D20 = -84.0° (c=1, EtOH) [1]
Chiral HPLC [2]: Data: MW55-3.jpg: (R)-PZQ / (S)-PZQ = 85:15
-> minor racemization
1H NMR Data: 1H NMR MW55-3.pdf: PZQ and a little side product -> comp. (rac)-PZQ

TLC of all experiments showed less side products (Rf= , ethyl acetate: hexane = 1:1, stain potassium permanganate)

[1] it was assumend that no side reaction happend - for the concentration of the solution the amount of the starting material was used.
[2] Chiral HPLC: Chiralcel OD-H, hexane/iso-propanol/Et3N = 60/40/0.1, 0.7 ml/min flow rate, RT: (R)-PZQ = 11.5 min, (S)-PZQ =14.5 min.

Results:
no racemization with Pd/C and Pd/BaSO4
minor racemization with Raney Ni
Attached Files
Scheme MW55.png
MW55-1.jpg
MW55-2.jpg
MW55-3.jpg
1H NMR MW55-3.pdf