General Organic Mechanisms Notes

Acids & Bases

Strengths of H-A are expressed on the pKa scale, where pKa = - log10 Ka. In order to have a unified scale for H-A and B strength, the acid strength of BH+ rather than base strength of B is usually listed. If required, the latter value is easily calculated from the former.

As acid strength increases, Ka increases, pKa decreases. As the base strength of B increases Kb increases and pKa (of BH+) increases.

Some pKa’s:

Factors Determining Acidity:

1. Weak A-H bond.
2. Electronegativity of A-H bond.
3. Stability of anion after H+ lost (drives equilibrium to the right), e.g. inductive or mesomeric stabilisation of the negative charge, or lower hybridisation. Also stereoelectronic effects, e.g. bridgeheads can prevent the molecule becoming planar.
4. Solvation effects.

Nucleophilic Substitution

Eliminations

Stereoelectronics of transition state:

E2 Reactions

Hoffmann / Saytzeff Ratio increases as:

1. Strength of B increases.
2. Electron withdrawal of L increases.
3. L- becomes a poorer leaving group.
4. Size of B increases.
5. Size of R or L increases.

E1 Reactions

If conditions are changed so that E2 is more favoured:

Other routes to alkenes include the Wittig Reaction (see Organoelements Notes) and the McMurray Coupling Reaction:

Also syn eliminations:

Note also that H-L does not have to be eliminated, can eliminate e.g. L-L:

Alkenes

Addition to C=C bonds can take a variety of pathways.

Stepwise addition via a non-bridged intermediate usually gives rise a mixture of syn and anti products, although the anti tends to dominate. HX and H-OH react by this pathway.

Bridged intermediates tend to be by X2 and HO-X, the halonium being formed in both cases. Anti addition then results.

Concerted addition is also known for a variety of reagents:

Hydroboration –

Mercuric Acetate –

Peroxyacids –

Osmium Tetroxide –

Ozone –

Alkynes

Alkynes can be synthesised from alkenes by first adding Br2 across the double bond, and then eliminating twice using NaNH2 in liquid NH3. Similarly, diketones can be converted to alkynes by adding hydrazine. This forms a diazo intermediate at each C=O bond, which rapidly eliminates 2N2 to leave an alkyne.

Their principle use is in carbon-carbon bond forming reactions, as the H is acidic due to the sp hybridised carbon, so metallation is easy. They can be subsequently reduced by Lindlar’s catalyst + H2, or Na in NH3 (methods give cis and trans respectively).

Alcohols

Chemistry of these is somewhat obvious. Particular reactions worth knowing are the methods of oxidation of 1,2-diols:

Carbonyls & Esters

Mechanisms for Ester Hydrolysis

There are actually 8 possible mechanisms for this. The terminology used is A/B for acid/base catalysed, then a subscript Ac/Al for acyl/alkyl bond cleavage respectively, and finally 1 or 2 for uni-/bi-molecular rate determining step. There are two unknown mechanisms of the 8, these are the AAl2 and BAc1. Some of the others are very uncommon as well.

BAC2 –

• Most common method for hydrolysis of simple alkyl esters (Me, Et, Ph, etc).
• 18O incorporation experiments show acyl-oxygen cleavage.
• OH- attack to form tetrahedral intermediate is rate determining.
• Carboxylic acid deprotonation renders reaction essentially irreversible.

BAL2 –

• Less common. Mechanism observed for Me esters and β-lactones.
• It requires a good nucleophile such as I- or PhSe-.
• Pyridine traps the CH3I as a salt to displace the equilibrium to the right.

AAc2 –

• Acid catalysed equivalent of BAC2 mechanism.
• Has been proven by 18O substitution and NMR studies.
• More commonly used in reverse in ester formation.

AAL1 –

• Mechanism observed for RCO2R’ where R’ can form a stable carbocation on alkyl-oxygen cleavage, e.g. R’ = tbutyl, CHPh2.
• Can be used in reverse for formation of these esters (e.g. RCO2H + 2-methylpropene + H+).

AAC1 –

• Occurs for RCO2R’ where R is bulky (i.e. a tetrahedral intermediate would be too hindered).
• Occurs via an acyl cation, and only in powerfully ionising solvents.

Meerwein-Ponndorf-Varley Reaction

Equilibrium reaction, so can be reversed – oxidising secondary alcohols to ketones by treatment with excess acetone (normally called Oppenhauer Oxidation).

Cannizzaro Reaction

Reformatsky Reaction

Stobbe Reaction

Darzen’s Reaction