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Racemization of PZQ and PZQamine
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23rd March 2011 @ 07:48
Racemization experiments on enantioenrichend S-(+)-PZQamine (MW49-13) with sodium naphthalide as a radical anion catalyst.

Scheme MW50-9.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)
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 MW50-9.pdf


Start time: 1:00 pm 24/03/2011
End time: 6:50 pm 24/03/2011

Preparation of sodium naphthalide (0.1 M solution in THF):
To a solution of naphthalene (128 mg, 1.00 mmol, M.W. = 128.2 g/mol) in THF (10 mL) was added sodium (23 mg, 1.00 mmol, M.W. = 23.0 g/mol) under a nitrogen atmosphere and stirred at r.t. -> no reaction, color should turn green
- added more sodium (23 mg, 1.00 mmol) -> shiny metal surface turned grey, after 2 h the metal surface began to turn greenish (moist solvent ?)
- after 5 h: solution turned green/brown
[M.W. sodium naphthalide 151.2 g/mol]

Start time: 6:50 pm 24/03/2011
End time: 10:00 pm 25/03/2011

Racemization of S-(+)-PZQamine (MW50-9):
To a solution of S-(+)-PZQamine (30 mg, 148 µmol, MW: 202.3 g/mol) in THF (3 mL) was added a solution of sodium naphthalide (297 µL of a 0.1 M solution, 29.7 µmol, 20 mol%) and stirred for 15 h at r.t.

Racemization of R-(-)-PZQ (MW55-5):
To a solution of R-(-)-PZQ (30 mg, 96.2 µmol, MW: 312 g/mol) in THF (3 mL) was added a solution of sodium naphthalide (192 µL of a 0.1 M solution, 19.2 µmol, 20 mol%) and stirred for 15 h at r.t.

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: 13.8 min.
HPLC MW55-5.jpg

-> no racemization

Results:
- no racemization or any reaction -> Na naphthalide already quenched before a reaction happend (?)

Repetition of the experiment:
Repetition: Racemization of S-(+)-PZQamine with sodium naphthalide (MW50-10)


References:
[1] Procedure for sodium naphthalide (Step C.): tert-BUTYL-tert-OCTYLAMINE, E. J. Corey and Andrew W. Gross, Organic Syntheses, Coll. Vol. 8, p.93 (1993); Vol. 65, p.166 (1987).

[2] Process for racemizing of optically active amines, T. Inoue and Y. Hirayama, United States Patent US005969186A, 1999.
Attached Files
Scheme MW50-9.png
HPLC MW55-5.jpg
HRAF MW50-9.pdf