Pictet-Spengler route to Praziquantel

 

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Summary and Conclusion
Reaction does not proceed in neat methanesulfonic acid at room temperature (3 hours). Recovered starting material. Cleaner than KAB18-1 initially used, suggesting starting material is more robust than expected.

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START: 15/03/12
FINISH: 15/03/12




Hazard and Risk Assessment


Previous/Related Experiments
AgOTf catalysed synthesis of 1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB20-1)
Synthesis of N-benzylidene-N-phenethylamine (KAB18-1)

Following Experiments
Synthesis of 1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB20-3)

Chemical Information
N-Benzylidene-N-phenethylamine (1, KAB18-1) - SMILES: N(=C/c1ccccc1)\CCc2ccccc2, InChI: InChI=1S/C15H15N/c1-3-7-14(8-4-1)11-12-16-13-15-9-5-2-6-10-15/h1-10,13H,11-12H2/b16-13+, InChIKey: OOBAKFDIGIHHOM-DTQAZKPQSA-N
1-Phenyl-1,2,3,4-tetrahydroisoquinoline (2, KAB20-2) - SMILES: c1ccc3c(c1)C(c2ccccc2)NCC3, InChI: InChI=1S/C15H15N/c1-2-7-13(8-3-1)15-14-9-5-4-6-12(14)10-11-16-15/h1-9,15-16H,10-11H2, InChIKey: PRTRSEDVLBBFJZ-UHFFFAOYSA-N
Methanesulfonic acid - SMILES: O=S(=O)(O)C, InChI: InChI=1S/CH4O3S/c1-5(2,3)4/h1H3,(H,2,3,4), InChIKey: AFVFQIVMOAPDHO-UHFFFAOYSA-N


Procedure
KAB18-1 (1.03 g, 4.92 mmol, 1 eq) was added portionwise to methanesulfonic acid (6.0 mL, 93 mmol, 20 eq) at 0 °C. The yellow reaction mixture was gradually warmed to rt and stirred for 3 hours.

After 3 hours, the deep red reaction mixture was poured over ice and made alkaline with NaOH solution (5 M), which resulted in formation of a white precipitate. The solid was filtered out and dried under a high vacuum (1.59 g, 154%).


Proton NMR indicated the recovered solid was starting material.

1H-NMR (300 MHz; CDCl3): δ 8.20 (s, 1H), 7.74-7.22 (m, 10H), 3.89 (t, J = 7.5 Hz, 2H), 3.04 (t, J = 7.5 Hz, 2H).

Summary and Conclusion
Reaction does not proceed in neat methanesulfonic acid at room temperature (3 hours). Recovered starting material. Cleaner than KAB18-1 initially used, suggesting starting material is more robust than expected.


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NOTES 15/03/12
- Yield >>>100%. Wet? Large water peak (1.57 ppm) in proton NMR (CDCl₃).

NOTES 17/03/12
- Going over recorded NMR of the compound. Not so sure if it's starting material. Aromatic region is missing 2 protons. Total integration gives 13 protons. Starting material has 15.

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