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22nd March 2012 @ 06:01
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Summary and Conclusion
Moderate yield (68%) and low conversion (9%) for the cyclisation reaction in neat methanesulfonic acid (140 °C, 20 hours).
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START: 22/03/12
FINISH: 26/03/12




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

Following Experiments

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, KAB20-4) - 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
A mixture of KAB18-1 (194 mg, 0.93 mmol, 1 eq) and methanesulfonic acid (1.2 mL, 18.5 mmol, 20 eq) was reflux heated at 140 °C from 17:20.
After 19 hours the reaction mixture was poured over ice, then basified with NaOH (6 M), which turned the solution cloudy white. The precipitate was too fine to filter, so the aqueous layer was extracted with EtOAc (3 × 30 mL) and diethyl ether (30 mL). The organic layer were combined, dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give crude KAB20-4 as a dark brown oil (132 mg, 68%).

1H-NMR (300 MHz; CDCl3)
Raw H-NMR crude KAB20-4
H-NMR crude KAB20-4


Imine proton of KAB18-1 starting material: δ 8.20
Proton of cyclised THIQ at C1, KAB20-4: δ 5.14

Ratio of starting material to product ~ 1:0.10 = 9% conversion.

Summary and Conclusion
Moderate yield (68%) and low conversion (9%) for the cyclisation reaction in neat methanesulfonic acid (140 °C, 20 hours).

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NOTES 24/03/12
- Need to NMR sample
- Used the last of the KAB18-1 sample.

NOTES 23/03/12
- Some white crystals formed partway up the condensing tube. Will NMR in addition to crude sample.

NOTES 26/03/12
- POST YIELD!
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Linked Posts
Attached Files
Scheme KAB20-4
Raw H-NMR crude KAB20-4
Raw H-NMR crude KAB20-4
H-NMR crude KAB20-4