Second Trimester
Lesson 21 focuses on several important functional groups and reactions in organic chemistry: aldehydes, ketones, imines, enamines, and Wittig reactions.
Aldehydes and ketones are carbonyl-containing compounds where the carbonyl group (C=O) is bonded to hydrogen or carbon atoms. Aldehydes have at least one hydrogen atom attached to the carbonyl carbon, making them highly reactive and susceptible to oxidation and nucleophilic addition reactions. Ketones, on the other hand, have two carbon atoms attached to the carbonyl carbon, rendering them slightly less reactive than aldehydes. Both aldehydes and ketones play pivotal roles in various organic synthesis reactions due to their ability to undergo nucleophilic addition.
Imines and enamines are nitrogen-containing compounds derived from the reactions of aldehydes or ketones with amines. Imines (Schiff bases) are formed when a primary amine reacts with an aldehyde or ketone, resulting in the replacement of the carbonyl oxygen with a nitrogen atom double-bonded to the carbon (C=N). Enamines are formed from secondary amines reacting with aldehydes or ketones, resulting in a nitrogen atom bonded to an alkene (C=C-N). These compounds are valuable intermediates in organic synthesis, especially in the formation of carbon-nitrogen bonds.
The Wittig reaction is a prominent method for synthesizing alkenes by reacting a phosphonium ylide with an aldehyde or ketone. The reaction involves the formation of a four-membered ring intermediate, the oxaphosphetane, which subsequently breaks down to yield the desired alkene and a phosphine oxide byproduct.
Mechanism of the Wittig Reaction:
Formation of the Ylide: The Wittig reaction begins with the preparation of a phosphonium ylide. This is achieved by treating a triphenylphosphine (PPh3) with an alkyl halide (R-X), resulting in the formation of a phosphonium salt. The salt is then deprotonated by a strong base, such as butyllithium (BuLi) or sodium hydride (NaH), to generate the ylide. The general structure of an ylide is Ph3P=CHR, where R is an alkyl or aryl group.
Addition to the Carbonyl Compound: The phosphonium ylide reacts with an aldehyde or ketone. The nucleophilic carbon of the ylide attacks the electrophilic carbon of the carbonyl group, leading to the formation of a four-membered ring intermediate called an oxaphosphetane.
Formation of the Alkene and Phosphine Oxide: The oxaphosphetane intermediate undergoes a rearrangement, breaking down to form the desired alkene and triphenylphosphine oxide (Ph3P=O). This step involves the simultaneous breaking of the P-C and C-O bonds in the oxaphosphetane.
Advantages and Applications:
Stereoselectivity: The Wittig reaction can be highly stereoselective, producing predominantly (E)- or (Z)-alkenes depending on the nature of the ylide and reaction conditions.
Versatility: It is applicable to a wide range of aldehydes and ketones, including those with various functional groups.
Control over Product Geometry: By choosing the appropriate ylide (stabilized or unstabilized), chemists can exert control over the geometry of the resulting double bond.