Pictet-Spengler route to Praziquantel

 

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Summary and Conclusion
The imine (KAB19-1) was facilely formed at room temperature upon addition of 3,4-dimethoxyphenethylamine to a concentrated mixture of benzaldehyde in diethyl ether.
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START: 13/03/12
FINISH: 15/03/12




Hazard and Risk Assessment


Following Experiments
Synthesis of 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB21-1)

Chemical Information
3,4-Dimethoxyphenethylamine (1) - SMILES: O(c1ccc(cc1OC)CCN)C, InChI: InChI=1S/C10H15NO2/c1-12-9-4-3-8(5-6-11)7-10(9)13-2/h3-4,7H,5-6,11H2,1-2H3, InChIKey: ANOUKFYBOAKOIR-UHFFFAOYSA-N.

Benzaldehyde (2)- SMILES: c1ccc(cc1)C=O, InChI: InChI=1S/C7H6O/c8-6-7-4-2-1-3-5-7/h1-6H, InChIKey: HUMNYLRZRPPJDN-UHFFFAOYSA-N.
N-[2-(3,4-Dimethoxyphenyl)ethyl]-1-phenylmethanimine (3, KAB19-1) SMILES: O(c1ccc(cc1OC)CC/N=C/c2ccccc2)C, InChI: InChI=1S/C17H19NO2/c1-19-16-9-8-14(12-17(16)20-2)10-11-18-13-15-6-4-3-5-7-15/h3-9,12-13H,10-11H2,1-2H3/b18-13+, InChIKey: HEYKSOUNCDDROU-QGOAFFKASA-N

Procedure
3,4-Dimethoxyphenethylamine (2 mL, 12 mmol, 1 eq) was added to stirring diethyl ether (4 mL) before benzaldehyde (1.2 mL, 12 mmol, 1 eq) was added slowly. The pale yellow solution turned a darker yellow and an miscible aqueous layer was visible in the bottom of the flask. After 20 minutes, the reaction mixture was dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give a yellow oil.

Proton NMR of the isolated product showed trace amounts of solvent and the benzaldehyde and 3,4-dimethoxyphenethylamine starting materials.

Summary and Conclusion
The imine (KAB19-1) was facilely formed at room temperature upon addition of 3,4-dimethoxyphenethylamine to a concentrated mixture of benzaldehyde in diethyl ether.

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NOTES 13/03/12
- Will need to repeat to acquire accurate yield for the procedure.
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