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16th March 2012 @ 00:38
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Summary and Conclusion
No cyclisation was observed after reflux heating KAB18-1 at 60 °C for 68 hours. Crude product was starting material, KAB18-1, of which 86% was recovered.
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START: 16/03/12
FINISH: 19/03/12




Hazard and Risk Assessment
As for KAB20-2 (here).

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

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

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, KAB20-3) - 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
16/03/12. KAB18-1 (480 mg, 2.30 mmol, 1 eq) was added to stirring methanesulfonic acid (3 mL, 46.2 mmol, 20 eq) at 0 °C. The reaction mixture was then warmed to 60 °C and reflux heated from 12:00.
As the KAB18-1 granules began to dissolve, the reaction mixture turned yellow. Within 30 minutes, the mixture was a dark red colour.
Reaction mixture (0 h)
Reaction mixture (30 min)


19/03/12. After 68 hours, the reaction mixture was removed from heat and poured over an ice water slurry. The reaction mixture was basified using NaOH (5 M), which resulted in precipitation of a white solid. The basic aqueous solution was extracted with diethyl ether (3 × 30 mL). The organic fractions were combined, dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give crude KAB20-3 as a brown oil (412 mg, 86%).

1H-NMR of the crude product indicated the isolated material was the KAB18-1 starting material.
Raw H-NMR crude KAB20-3

The product was taken no further.

Summary and Conclusion
No cyclisation was observed after reflux heating KAB18-1 at 60 °C for 68 hours. Crude product was starting material, KAB18-1, of which 86% was recovered.

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NOTES 19/03/12
- Flask: 51.1456 g

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Linked Posts
Attached Files
Scheme KAB20-3
Reaction mixture (0 h)
Reaction mixture (30 min)
Raw H-NMR crude KAB20-3