proline catalyzed aldol reaction
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Proline Catalyzed Aldol Reaction(Organo-catalysis)
By :
Hemanta Sarmah(09MS001)
Soumalya Sinha(09MS006)
Debtanu Chakraborty(09MS031)
Aldol Reaction :
It is the type of reaction that produces a β-hydroxy carbonylcompound from a mixture to two or more carbonyl compounds , inpresence of a suitable catalyst.
The catalyst could be either of the following:
Base or Acid
Other organic catalysts ( If the reaction is organocatalytic )
The product formed is called an aldol.
(Aldol = Aldehyde + Alcohol)
An example : (of Aldol Condensation)
Enol/enolate ion + a carbonyl compound β- hydroxyaldehyde /
β-hydroxyketone
What’s Organo-catalysis ?
Organocatalysis (or metal –free catalysis ) uses small organic molecules predominantly composed of C, H, O, N, S and P to accelerate chemical reactions.
In simple words, Organocatalysis refers to a form of catalysis, whereby the rate of a chemical reaction is increased by an organic catalyst.
For Example :
CH3CHOCN—CN ----------------> CO(NH2)—CO(NH2)
H2O (rt)
: PROS and CONS :
Advantages :
It gives us enantio-selective product
A very little amount( equivalent) of catalyst is needed to carry the reaction
Low cost
Lack of sensitivity to moisture and oxygen
No metal contamination
Multiple stereocenter formation
Disadvantages :
It’s no CHEMICAL STUNT ! Requires Time and patience
Slower than metal catalyzed reactions
Enantio-selective ! But why ?
Different enantiomers or diastereomers of a molecule often have different biological activity
Synthesis of chiral drugs : $18 billion annually (growing @ 9% p.a)
Predicted that 75% of the drugs will be sold as single enantiomers in the coming years.
One day-to-day life example :
How many of you still take Cetirizine or Cetirizine Hypochlorite ?
Today we have the levorotary enantiomer of cetirizine, known as levocetirizine, that is far more effective and less damaging to the body.
Enzyme
recognition
Natural Epinephrin(adrenaline)
UnnaturalEpinephrin
Organo-catalysts are generally low molecular weight compounds.
Basically they can be classified as chiral and achiral ones. Here are few:
Organo-catalysts are generally low molecular weight compounds.
Basically they can be classified as chiral and achiral ones. Here are few:
Our Project :
Aldol condensation of Cyclohexanone and Nitro-
substituted benzaldehyde in presence of L-Proline.
Materials Used : 15ml Glass Vial (for carrying out the reactions)
Round Bottom Flask
Magnetic Bead and Stirrer
Rotavapour (for removing excess solvent from solution)
Testube , Capillary tube, TLC film, pencil and scale
UV lamp
Apparatus for Flash Chromatography
Reagents Used :
Acetone
DMSO
Ethyl Acetate
Here’s the reaction ingredients !!
Starting Compound(s) :
Cyclohexanone 98.150 g/mol
3-nitro benzaldehyde 151.12 g/mol
4-nitro benzaldehyde 151.12 g/mol
Organocatalyst :
L-proline 115.13 g/mol
Solvent :
PtsOH 190.22 g/mol
Procedure:
In a vial, we mixed 7.61mg of L-Proline, 12.57mg of PtsOH,0.6613mmol(100mg) of 3-Nitrobenzaldehyde and 300 mg of Cyclohexanone all together.
In another vial, 0.6613mmol(100mg) of 4-Nitrobenzaldehyde was taken while all the other ingredients (of vial 1) were repeated with the exact amounts.
Now, both the vials were stirred with the magnetic bar for 3 days.
The solution was then run on a TLC plate and it resulted in formation of at least 3 distinct bands for both the reactions when viewed in UV light chamber.
To purify the product, Flash Chromatography was undertaken. All the products were isolated, solidified using Rotavapour and sent for NMR Spectroscopy.
(1)
Reaction of Cyclohexanone with 4-nitrobenzaldehyde
O
NO2C
O
H
Reaction Mechanism :
(2)
Reaction of Cyclohexanone with 3-nitrobenzaldehyde
O
C
O
H
No2
`
Calculations :
Sl.No
Substrate Formula wt. Mass(gm)
No. of milimoles
No. of equivalents
1 3-nitro benzaldehyde
151.12 100 0.6613 1
2 4-nitrobenzaldehyde
151.12 100 0.6613
Analysis with Chromatography :
TLC analysis :
1H NMR spectra for 4-nitrobenzaldehyde:
OOH
N+
O
O-
2.27;2.17
1.81;1.78
1.85;1.75
1.88;1.63
2.68
7.45 8.12
8.127.45
4.72
2.0
1H NMR spectra for 3-nitrobenzaldehyde:
Acknowledgements :
We are extremely grateful to
Dr. Debasish Haldar and
Dr. Jyotirmayee Dash for
having allowed us this
wonderful opportunity as a
part of the lab course.
Acknowledgements :
We are extremely grateful to Mr.
Sushovan Paladhi (PhD student)
and Mr. Ganesh Midya (PhD
student) for their immense help
and support throughout the
semester and specially during the
project tenure.
Thank you !!
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