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27th April 2012 @ 08:07
START: 27/04/12
FINISH:

Increasing reagent concentration (decreasing rxn volume).
Scheme%20KAB25-2.png

Hazard and Risk Assessment
As for KAB25-2 here:
Hazard and Risk Assessment KAB25-2


Previous Experiments
Yb(OTf)3 catalysed PS to give 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB25-1)
Lewis acid-catalyst screen for the PS reaction to give KAB21 and KAB24

Following Experiments
Yb(OTf)3 catalysed PS reaction to give 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB21-9)

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.


Procedure
(All glassware was ovendried prior to use.)
26/04/12. Yb(OTf)3 (120 mg, 0.194 mmol) was added to a 3-necked flask containing well dried 3Å powdered MS under a nitrogen atmosphere. Dry toluene (5 mL) was before the sequential addition of benzaldehyde (0.10 mL, 0.97 mmol) and 3,4-dimethoxyphenethylamine (0.16 mL, 0.97 mmol). The reaction mixture was reflux heated to 110 °C from 17:10.
Reaction mixture (5 min)
Reaction mixture (20 min)
Reaction mixture (63 h)


Monitoring the Reaction Progress by TLC
All TLCs were eluted with 15%, MeOH/DCM, v/v and stained with ninhydrin. Lane 19-2 corresponds to the isolatable imine intermediate and 25-3 corresponds to the reaction mixture. Co = cospot.
TLC of reaction mixture (10 min)


Unsure of TLC at 0820 30/04/12
- 0.5 mL of reaction mixture was extracted then worked up. 2 mL sat NaHCO3. EtOAc 2 × 2 mL. MgSO4.

After 3 days, the reaction mixture was removed from heat and allowed to cool. After dilution with EtOAc (20 mL), the mixture was quenched with saturated sodium bicarbonate solution (20 mL). The organic fraction was isolated and the basic aqueous fraction was extracted with EtOAc (3 × 20 mL). The organic fractions were combined, dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give crude KAB25-3 as thick yellow oil (291 mg, 111%).

Summary and Conclusion


References
[1] K. Manabe, D. Nobutou, S. Kobayashi, Bioorg. Med. Chem. 2005, 13, 5154-5158.
[2] M. J. V. Eynden, K. Kunchithapatham, J. P. Stambuli, Journal of Organic Chemistry 2010, 75, 8542-8549.


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NOTES 30/04/12
- Still unable to upload files. Hence missing TLC photos.
- Flask: 47.1254
- Crude product smelled faintly like benzaldehyde
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Attached Files
Reaction mixture (63 h)
Reaction mixture (5 min)
Reaction mixture (20 min)
TLC of reaction mixture (10 min)
TLC of reaction mixture (25 min)