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 Birch Reduction offers access to substituted 1,4-cyclohexadienes.

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.

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.

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.

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:

The [4+2]-cycloaddition of a conjugated diene and a dienophile (an alkene or alkyne), an electrocyclic reaction that involves the 4 ?-electrons of the diene and 2 ?-electrons of the dienophile. The driving force of the reaction is the formation of new ?-bonds, which are energetically more stable than the ?-bonds.

In the case of an alkynyl dienophile, the initial adduct can still react as a dienophile if not too sterically hindered. In addition, either the diene or the dienophile can be substituted with cumulated double bonds, such as substituted allenes.

With its broad scope and simplicity of operation, the Diels-Alder is the most powerful synthetic method for unsaturated six-membered rings.

A variant is the hetero-Diels-Alder, in which either the diene or the dienophile contains a heteroatom, most often nitrogen or oxygen. This alternative constitutes a powerful synthesis of six-membered ring heterocycles.

Overlap of the molecular orbitals (MOs) is required:

Overlap between the highest occupied MO of the diene (HOMO) and the lowest unoccupied MO of the dienophile (LUMO) is thermally allowed in the Diels Alder Reaction, provided the orbitals are of similar energy. The reaction is facilitated by electron-withdrawing groups on the dienophile, since this will lower the energy of the LUMO. Good dienophiles often bear one or two of the following substituents: CHO, COR, COOR, CN, C=C, Ph, or halogen. The diene component should be as electron-rich as possible.

There are ?inverse demand? Diels Alder Reactions that involve the overlap of the HOMO of the dienophile with the unoccupied MO of the diene. This alternative scenario for the reaction is favored by electron-donating groups on the dienophile and an electron-poor diene.

The reaction is diastereoselective.

Cyclic dienes give stereoisomeric products. The endo product is usually favored by kinetic control due to secondary orbital interactions.

The Lewis or Brønstedt acid-catalyzed esterification of carboxylic acids with alcohols to give esters is a typical reaction in which the products and reactants are in equilibrium.

The equilibrium may be influenced by either removing one product from the reaction mixture (for example, removal of the water by azeotropic distillation or absorption by molecular sieves) or by employing an excess of one reactant.

Addition of a proton (e.g.: p-TsOH, H₂SO₄) or a Lewis acid leads to a more reactive electrophile. Nucleophilic attack of the alcohol gives a tetrahedral intermediate in which there are two equivalent hydroxyl groups. One of these hydroxyl groups is eliminated after a proton shift (tautomerism) to give water and the ester.

The Grignard Reaction is the addition of an organomagnesium halide (Grignard reagent) to a ketone or aldehyde, to form a tertiary or secondary alcohol, respectively. The reaction with formaldehyde leads to a primary alcohol.

Grignard Reagents are also used in the following important reactions: The addition of an excess of a Grignard reagent to an ester or lactone gives a tertiary alcohol in which two alkyl groups are the same, and the addition of a Grignard reagent to a nitrile produces an unsymmetrical ketone via a metalloimine intermediate. (Some more reactions are depicted below)

While the reaction is generally thought to proceed through a nucleophilic addition mechanism, sterically hindered substrates may react according to an SET (single electron transfer) mechanism:

With sterically hindered ketones the following side products are received:

The Grignard reagent can act as base, with deprotonation yielding an enolate intermediate. After work up, the starting ketone is recovered.

A reduction can also take place, in which a hydride is delivered from the ?-carbon of the Grignard reagent to the carbonyl carbon via a cyclic six-membered transition state.

With carboxylic acid chlorides:

Esters are less reactive than the intermediate ketones, therefore the reaction is only suitable for synthesis of tertiary alcohols using an excess of Grignard Reagent:

With nitriles:

With CO₂ (by adding dry ice to the reaction mixture):

With oxiranes: