Aldol Addition Reaction
'Aldol' is an abbreviation of aldehyde and alcohol. When the enolate of an aldehyde or a ketone reacts at the ?-carbon with the carbonyl of another molecule under basic or acidic conditions to obtain ?-hydroxy aldehyde or ketone, this reaction is called Aldol Reaction.
Mechanism
Under conditions of kinetic control, the mixed Aldol Addition can be used to prepare adducts that are otherwise difficult to obtain selectively. This process begins with the irreversible generation of the kinetic enolate, e.g. by employing a sterically hindered lithium amide base such as LDA (lithium diisopropylamide). With an unsymmetrically substituted ketone, such a non-nucleophilic, sterically-demanding, strong base will abstract a proton from the least hindered side. Proton transfer is avoided with lithium enolates at low temperatures in ethereal solvents, so that addition of a second carbonyl partner (ketone or aldehyde) will produce the desired aldol product.
Aldol Condensation
In some cases, the adducts obtained from the Aldol Addition can easily be converted (in situ) to ?,?-unsaturated carbonyl compounds, either thermally or under acidic or basic catalysis. The formation of the conjugated system is the driving force for this spontaneous dehydration. Under a variety of protocols, the condensation product can be obtained directly without isolation of the aldol.
The aldol condensation is the second step of the Robinson Annulation.
Mechanism
For the addition step see Aldol Addition.
Azo Coupling
Azo coupling is the most widely used industrial reaction in the production of dyes, lakes and pigments. Aromatic diazonium ions acts as electrophiles in coupling reactions with activated aromatics such as anilines or phenols. The substitution normally occurs at the para position, except when this position is already occupied, in which case ortho position is favoured. The pH of solution is quite important; it must be mildly acidic or neutral, since no reaction takes place if the pH is too low.
Mechanism
Balz-Schiemann Reaction
The conversion of aryl amines to aryl fluorides via diazotisation and subsequent thermal decomposition of the derived tetrafluoroborates or hexafluorophosphates. The decomposition may also be induced photochemically.
Mechanism
The mechanism of the Balz-Schiemann reaction remains obscure. A possible pathway is shown below:
Beckmann Rearrangement
An acid-induced rearrangement of oximes to give amides.
This reaction is related to the Hofmann and Schmidt reactions and the curtius rearrangement, in that an electropositive nitrogen is formed that initiates an alkyl migration.
Mechanism
Oximes generally have a high barrier to inversion, and accordingly this reaction is envisioned to proceed by protonation of the oxime hydroxyl, followed by migration of the alkyl substituent "trans" to nitrogen. The N-O bond is simultaneously cleaved with the expulsion of water, so that formation of a free nitrene is avoided.
Birch Reduction
The Birch Reduction offers access to substituted 1,4-cyclohexadienes.
Mechanism
The question of why the 1,3-diene is not formed, even though it would be more stable through conjugation, can be rationalized with a simple mnemonic. When viewed in valence bond terms, electron-electron repulsions in the radical anion will preferentially have the nonbonding electrons separated as much as possible, in a 1,4-relationship.
This question can also be answered by considering the mesomeric structures of the dienyl carbanion:
The numbers, which stand for the number of bonds, can be averaged and compared with the 1,3- and the 1,4-diene. The structure on the left is the average of all mesomers depicted above followed by 1,3 and 1,4-diene:
The difference between the dienyl carbanion and 1,3-diene in absolute numbers is 2, and between the dienyl carbanion and 1,4-diene is 4/3. The comparison with the least change in electron distribution will be preferred.
Reactions of arenes with +I- and +M-substituents lead to the products with the most highly substituted double bonds:
The effect of electron-withdrawing substituents on the Birch Reduction varies. For example, the reaction of benzoic acid leads to 2,5-cyclohexadienecarboxylic acid, which can be rationalized on the basis of the carboxylic acid stabilizing an adjacent anion:
Alkene double bonds are only reduced if they are conjugated with the arene, and occasionally isolated terminal alkenes will be reduced.
Cannizzaro Reaction
This redox disproportionation of non-enolizable aldehydes to carboxylic acids and alcohols is conducted in concentrated base.
?-Keto aldehydes give the product of an intramolecular disproportionation in excellent yields.
Mechanism
An interesting variant, the Crossed Cannizzaro Reaction, uses formaldehyde as reducing agent:
At the present time, various oxidizing and reducing agents can be used to carry out such conversions (with higher yields), so that today the Cannizzaro Reaction has limited synthetic utility except for the abovementioned conversion of ?-keto aldehydes.
The Cannizzaro Reaction should be kept in mind as a source of potential side products when aldehydes are treated under basic conditions.
Clemmensen Reduction
The Clemmensen Reduction allows the deoxygenation of aldehydes or ketones, to produce the corresponding hydrocarbon.
The substrate must be stable to strong acid. The Clemmensen Reduction is complementary to the Wolff-Kishner Reduction, which is run under strongly basic conditions. Acid-labile molecules should be reduced by the Wolff-Kishner protocol.
Mechanism
The reduction takes place at the surface of the zinc catalyst. In this reaction, alcohols are not postulated as intermediates, because subjection of the corresponding alcohols to these same reaction conditions does not lead to alkanes. The following proposal employs the intermediacy of zinc carbenoids to rationalize the mechanism of the Clemmensen Reduction:
Diazotisation
The nitrosation of primary aromatic amines with nitrous acid (generated in situ from sodium nitrite and a strong acid, such as hydrochloric acid, sulfuric acid, or HBF4) leads to diazonium salts, which can be isolated if the counterion is non-nucleophilic.
Diazonium salts are important intermediates for the preparation of halides (Sandmeyer Reaction, Schiemann Reaction), and azo compounds. Diazonium salts can react as pseudohalide-type electrophiles, and can therefore be used in specific protocols for the Heck Reaction or Suzuki Coupling. The intermediates resulting from the diazotization of primary, aliphatic amines are unstable; they are rapidly converted into carbocations after loss of nitrogen, and yield products derived from substitution, elimination or rearrangement processes.
Mechanism
more reactions coming in Part II,,,,,,,,,,,
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