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30th October 2016 @ 17:06

Running Date of experiment 10-11/10/16

Synthesis of 2-(3-Bromo-phenyl)-[1,3]dioxolane from 3-bromobenzaldehyde

Week 3 Experiment 2:

 3-bromobenzaldehyde                       ethane-1,2-diol               2-(3-Bromo-phenyl)-[1,3]dioxolane    

Reagent

Equivalent

Molecular Weight

mmol

Quantity

3-Bromobenzaldehyde

185.02

10.8

2 g

ethane-1,2-diol

62.07

54

3.02 mL

toluene-4-sulfonic acid monohydrate

0.05 

190.22

0.54

93 mg

toluene

 

92.14

-

40 mL

saturated sodium bicarbonate

-

84.0066

-

-

ethyl acetate

-

81.11

-

-

brine

-

58.44

-

-

anhydrous magnesium sulfate

-

120.361

-

-

 Following the first weeks failed attempt to obtain the desired product it was decided to add a protecting group to the bromobenzaldehyde. This means that the overall reaction has 3 steps. This experiment is step 1.

The steps incude:

  1. Adding the protecting group to the bromobenzaldehyde.
  2. Coupling the protected bromobenzaldehyde with morpholine.
  3. Removing the protecting group from the product produced in step 2.

Experimental Procedure:

3-Bromobenzaldeyde (2 g, 10.8 mmol) was dissolved with ethane - 1,2 – diol (3.02 mL, 54 mmol) and tosylic acid (93 mg, 0.54 mmol) in toluene (40 mL). The solution was then refluxed overnight at 150 ° and TLC (Pet ether: ethyl acetate, 60: 40) was used to confirm the reaction had gone to completion.

The product was extracted using ethyl acetate and the organic layer was washed with brine. Next the organic layer was dried with anhydrous magnesium sulfate and this was followed by the product being evaporated in vacuo. An NMR was then taken of this crude product.

The NMR did produce a result however the yield was so small there was no possibility of the other 2 steps of the overall reaction being completed. So, it was decided that the same experiment would be carried out in a larger quantity using the cheaper staring material benzaldehyde.

Pic 6.png

Reference: Patent(EP1782811 A1, 2007, Page/ Page Column)

 

Attached Files
25th October 2016 @ 21:34

Running Date of experiment: 03-04/10/16

Synthesis of 3-(4-Morpholinyl)benzaldehyde from 3-Bromobenzaldehyde and Morpholine via Buchwald – Hartwig Coupling

Week 2 Experiment 1:

 

Reagent

Equivalent

Molecular Weight

mmol

Quantity

3-Bromobenzenaldehyde

1

185.02

1.08

0.2 g

Toluene

-

92.14

-

2 mL

Pd(dba)2

0.03

575

0.0341

19.6 mg

Morpholine

0.81

87.12

0.872

0.076 mL

(+-)-BINAP

0.04

622.67

0.0429

0.0267 g

NaO-t-Bu

1.5

96.1

1.62

0.156 g

 

Experimental Procedure

To 3-bromobenzaldehyde (0.2 g, 1.08 mmol) was added toluene (2 mL) and the solution degassed with N2 and an N2 atmosphere maintained. Morpholine (0.076 mL, 0.872 mmol) was then added followed by BINAP (0.0267 g, 0.0429 mmol) and Pd(dba)2 (19.6 mg, 0.0341 mmol). This mixture was then stirred for an hour at 70 °C and TLC (Pet ether: Ethyl acetate, 60:40) was used to monitor the progress of the reaction.

Pic 2.png

Pic 3.png

The TLC after an hour showed no evidence of the reaction taking place so the reaction was degassed again for 15 minutes and left to heat overnight. TLC anaysis was carried out in the morning and there was evidence a reaction had taken place so the reaction was diluted ethyl acetate and water. The layers were separated, the organic phase dried (MgSO4), filtered and the solvent removed in vacuo. Crude 1H NMR was collected on the product. 

Pic 4.png

The NMR did not produce the desired product, so it was decided a different root would be taken.

 References:

1. C. Fattorusso, G. Campiani, G. Kukreja, M. Persico, S. Butini, M. Romano, M. Altarelli, S. Ros, M. Brindisi, L. Savini, E. Novellino, V. Nacci, E. Fattorusso, S. Parapini, N. Basilico, D. Taramelli, V. Yardley, S. Croft, M. Borriello and S. Gemma, J. Med. Chem., 2008, 51, 1333-1343.

 

Attached Files