Aldol reaction

Aldol Condensation

1. BY Dr . G.C.Wadhawa DEPARTMENT OF CHEMISTRY K. B. P . College,Vashi,Navimumbai Aldol Condensation

2. 1 . Aldol Condensation Aldehydes having α- hydrogen undergo self-condensation on warming with dilute or mild base to give β-hydroxy aldehydes, called aldols (aldehyde+alcohol). This reaction is known as aldol condensation.

3. The reagent such as dilute sodium hydroxide, aqueous alkali carbonate, alkali metal alkoxide, etc., may be used. Aldol condensation has broad scope. It can occur between two identical or different aldehydes. Two identical or different ketones. An aldehyde and a ketone . Aldehyde or Ketone may aromatic or aliphatic When the condensation is between two different carbonyl compounds, it is called as crossed aldol condensation.

4. Mechanism reactions as follows

5. Reagents: commonly a base such as NaOH or KOH is added to the aldehyde. The reaction involves an aldehyde enolate reacting with another molecule of the aldehyde. Remember enolates are good nucleophiles and carbonyl C are good electrophiles. Since the pKa of an aldehyde is close to that of NaOH, both enolate and aldehyde are present simultaneously. The products of these reactions are β- hydroxyaldehydes or aldehyde-alcohols = aldols .

6. Why formal aldehyde does not give aldol reaction in alkaline medium? For a carbonyl compound to undergo aldol condensation, the necessary condition is that it MUST possess at-least 1 "alpha-hydrogen" (an alpha-hydrogen is a hydrogen attached to an alpha-carbon, while an alpha carbon is the carbon attached DIRECTLY to the functional group) since formaldehyde(i-e HCHO) has only 1 carbon which is the carbonyl carbon (i-e the functional group) and there is no alpha-carbon present and hence no alpha-hydrogen, so formaldehyde doesn't undergo aldol condensation. e.g Acetaldehyde can undergo aldol condensation since it has alpha- hydrogens . - The 2 hydrogens present in the formaldehyde molecule are not alpha- hydrogens ; they are simply the hydrogens attached to the functional group.

7. What is an alpha hydrogen atom needed for aldol condensation reaction to occur? Due to the acidic nature of α-hydrogen of aldehydes and ketones, they undergo a number of reactions. This acidity is because of the strong electron withdrawing nature of the carbonyl groups and resonance stabilization of the conjugate base. - Because, the C-H proton is not acidic enough . Further, carbonyl group of aldehyde is highly electrophilic (hard electrophile) hence the base (hard nucleophile) prefers to attack the carbonyl carbon leading to alcohol & acid. - So, in-order to get the aldol product, the presence of alpha hydrogens is necessary. These hydrogens are more acidic than the hydrogen attached to the carbonyl group.

8. Formaldehyde O HCH formaldehyde cannot form an enolate formaldehyde is extremely reactive toward nucleophilic addition

9. Formaldehyde O HCH + (CH 3 ) 2 CHCH 2 CH O 3 2 (CH ) CHCHCH O CH 2 OH (52%) K 2 CO 3 wate r - ether

10. Aromatic Aldehydes CH 3 O CH O aromatic aldehydes cannot form an enolate

11. Aromatic Aldehydes CH 3 O CH O + CH 3 CCH 3 O NaOH, H 2 O 30°C CH 3 O CH CHCCH 3 O (83%)

12. What is the product? There are 4 possibilities because the reaction mixture contains the two aldehydes plus the enolate of each aldehyde. NaOH CH 3 CH O O + CH 3 CH 2 CH

13. Intramolecular Aldol Condensation Na 2 CO 3 , H 2 O heat O O O O (96%) via: OH

14. References: http://en.wikipedia.org/wiki/Aldol_condensation http://www.organic-chemistry.org/namedreactions/aldol-condensation.shtm http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch18/ch18-3-4.html http://www.usask.ca/chemistry/courses/255/laboratory/aldol.htm