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27th February 2011 @ 00:08
Hydrolysis of racemic praziquantel (PZQ) was undertaken in order to isolate racemic praziquanamine (PZQ amine). Racemic PZQ was subjected to 0.5 M, 1 M, and 2 M HCl conditions, respectively, in ethanol under a 23 hour reflux.

PZQ Hydrolysis BM 1-1


Start Time: 13:15 17/02/11
End Time: 18:00 18/02/11

0.5 M HCl
To a mixture of 30 mL 0.5 M HCl and 7.5 mL anhydrous ethanol was added PZQ (1.0102 g, 3.23 mmol; M.W. = 312.41 g/mol). The mixture was then stirred and heated to reflux for 23 hours.

Work-up:
The reaction was allowed to cool to room temperature, upon which it was washed with 10 mL of EtOAc. Upon cooling in an ice bath, the solution was treated with 6N NaOH until the pH of the solution was determined to be 12 (using pH paper). The solution was then extracted twice with 15 mL of methylene dichloride and the combined organic layers were subsequently washed with brine (pH 12). The organic layers were then dried with anhydrous sodium sulfate, upon which the solvent was evaporated off using a rotary evaporator.

The reaction yielded a clear, colorless oil. The oil solidified after approximately 45 minutes to yield a solid, yellowish-white powder.

Oil Yield: 0.9716 g (4.80 mmol; 149%)
(Solid yield not determined because a substantial amount of the product was immediately utilized in the next experiment involving PZQ amine resolution before the product solidified)

TLC (Silica; 1:1 Hexanes : EtOAc): 2 spots; Rf1 = 0.31, Rf2 = 0.69
IR (KBr pellet): 3319.93 cm-1, 3052.72 cm-1, ~2900 cm-1, 1635.34 cm-1, 1496.75 cm-1, 1440.69 cm-1, 1252.94 cm-1, 1063.47 cm-1
1H NMR (300 MHz, CDCl3): (δ 7.2 ppm), (δ 5.3 ppm), (δ 4.9 ppm), (δ 4.1 ppm), (δ 3.7 ppm), (δ 3.6 ppm), (δ 2.9 ppm), (δ 2.0 ppm), (δ 1.7 ppm), (δ 1.1 ppm), (δ 0.0 ppm)


1 M HCl
To a mixture of 30 mL 1 M HCl and 7.5 mL anhydrous ethanol was added PZQ (1.0069 g, 3.22 mmol; M.W. = 312.41 g/mol). The mixture was then stirred and heated to reflux for 23 hours.

Work-up:
The reaction was allowed to cool to room temperature, upon which it was washed with 10 mL of EtOAc. Upon cooling in an ice bath, the solution was treated with 6N NaOH until the pH of the solution was determined to be 12 (using pH paper). The solution was then extracted twice with 15 mL of methylene dichloride and the combined organic layers were subsequently washed with brine (pH 12). The organic layers were then dried with anhydrous sodium sulfate, upon which the solvent was evaporated off using a rotary evaporator.

The reaction yielded a clear, colorless oil. The oil solidified after approximately 45 minutes to yield a solid, yellowish-white powder.

Oil Yield: 0.7940 g (3.92 mmol; 122%)
(Solid yield not determined because a substantial amount of the product was immediately utilized in the next experiment involving PZQ amine resolution before the product solidified)

TLC (Silica; 1:1 Hexanes : EtOAc): 1 spot; Rf = 0.70
IR (KBr pellet): 3314.18 cm-1, 3052.74 cm-1, ~2900 cm-1, 1635.24 cm-1, 1496.98 cm-1, 1440.31 cm-1, 1253.05 cm-1, 1063.12 cm-1
1H NMR (300 MHz, CDCl3): (δ 7.2 ppm), (δ 5.3 ppm), (δ 4.8 ppm), (δ 4.1 ppm), (δ 3.7 ppm), (δ 3.5 ppm), (δ 2.9 ppm), (δ 2.0 ppm), (δ 1.8 ppm), (δ 1.1 ppm), (δ 0.0 ppm)


2 M HCl
To a mixture of 30 mL 2 M HCl and 7.5 mL anhydrous ethanol was added PZQ (1.0012 g, 3.21 mmol; M.W. = 312.41 g/mol). The mixture was then stirred and heated to reflux for 23 hours.

Work-up:
The reaction was allowed to cool to room temperature, upon which it was washed with 10 mL of EtOAc. Upon cooling in an ice bath, the solution was treated with 6N NaOH until the pH of the solution was determined to be 12 (using pH paper). The solution was then extracted twice with 15 mL of methylene dichloride and the combined organic layers were subsequently washed with brine (pH 12). The organic layers were then dried with anhydrous sodium sulfate, upon which the solvent was evaporated off using a rotary evaporator.

The reaction yielded a clear, colorless oil. The oil solidified after approximately 45 minutes to yield a solid, yellowish-white powder.

Oil Yield: 0.6761 g (3.92 mmol; 104%)
(Solid yield not determined because a substantial amount of the product was immediately utilized in the next experiment involving PZQ amine resolution before the product solidified)

TLC (Silica; 1:1 Hexanes : EtOAc): 1 spot; Rf = 0.74
IR (Thin Film): 3310.70 cm-1, 3049.68 cm-1, ~2900 cm-1, 1735.49 cm-1, 1638.21 cm-1, 1459.31 cm-1, 1439.15 cm-1, 1248.91 cm-1, 1047.04 cm-1
1H NMR (300 MHz, CDCl3): (δ 7.2 ppm), (δ 5.3 ppm), (δ 4.8 ppm), (δ 4.1 ppm), (δ 3.7 ppm), (δ 3.6 ppm), (δ 2.9 ppm), (δ 2.0 ppm), (δ 1.7 ppm), (δ 1.2 ppm), (δ 0.0 ppm)

References:
(1) Woelfe, M. et al. "The Resolution of Praziquantel". 2011. http://openwetware.org/wiki/Todd:PZQ_Resolution
Attached Files
PZQ Hydrolysis BM 1-1
Comments
Re: Hydrolysis of Racemic Praziquantel (PZQ) at Varying HCl Concentrations (BM 1-1) by Matthew Todd
3rd March 2011 @ 22:46
Interesting that the crude product masses decrease the stronger the acid you used. Any idea what the extra mass is?
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Re: Hydrolysis of Racemic Praziquantel (PZQ) at Varying HCl Concentrations (BM 1-1) by Bojan Milic
1st April 2011 @ 03:11
Dr. Todd,

I apologize for not responding for so long, but I did not notice that there was actually a comment here until now.

The extra mass is almost certainly unevaporated solvent (DCM).

Regards,

Bojan Milic
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