2. Neucleophile
As electron pair donors, nucleophiles must
either contain an electron pair that is easily
available because it is nonbonding or they
must contain a bonding electron pair that
can be donated from the bond involved and
thus be made available to the reaction
partner.
From this it follows that nucleophiles are
usually anions or neutral species but not
cations.
3. Good and Poor Nucleophiles
Within a group of nucleophiles that
attack at the electrophile with the same
atom, the nucleophilicity decreases with
decreasing basicity of the nucleophile
Nucleophilicity is a measure of how
readily a compound (a nucleophile) is
able to attack an electron-deficient atom.
7. The nucleophilicity of a given nucleophilic center is
increased by attached heteroatoms that possess
free electron pairs (-effect)
8. Nucleophilic Aliphatic
substitution
To ensure that reaction occurs in homogeneous solution, solvents are
chosen that dissolve both the alkyl halide and the ionic salt. The alkyl
halide substrates are soluble in organic solvents, but the salts often are
not. Inorganic salts are soluble in water, but alkyl halides are not. Mixed
solvents such as ethanol–water mixtures that can dissolve enough of
both the substrate and the nucleophile to give fairly concentrated
solutions are frequently used. Many salts, as well as most alkyl halides,
possess significant solubility in dimethyl sulfoxide (DMSO), which makes
this a good medium for carrying out nucleophilic substitution reactions.
10. The SN2 Mechanism
a single step process
Involves no intermediates
Involves only one transition state, which is of
low polarity
Follows second order (bimolecular) kinetics.
That is, rate=k[substrate][nucleophile]
backside attack
16. The Effect of the Solvent
In a protic solvent, is the smallest atom the poorest
nucleophile even though it is the strongest base.
Protic solvents are hydrogen bond donors.
The interaction between the ion and the dipole of the
protic solvent is called an ion–dipole interaction.
Because the solvent shields the nucleophile, at least
one of the ion–dipole interactions must be broken
before the nucleophile can participate in a SN2
reaction.
Weak bases interact weakly with protic
solvents, whereas strong bases interact more
strongly because they are better at sharing their
electrons.
20. AN ENZYME-CATALYZED
NUCLEOPHILIC SUBSTITUTION
OF AN ALKYL HALIDE
Enzymes that catalyze these reactions are
known as haloalkane dehalogenases.
The haloalkane dehydrogenase is believed to
act by using one of its side-chain carboxylates
to displace chloride by an SN2 mechanism
21.
22. THE SN1 NUCLEOPHILIC
SUBSTITUTION
Hughes and Ingold observed that the
hydrolysis of tert-butyl bromide, which
occurs readily, is characterized by a
first-order rate law:
25. Experimental Evidence
1. The rate law shows that the rate of the reaction
depends only on the concentration of the alkyl halide. This
means that we must be observing a reaction whose rate-
determining step involves only the alkyl halide.
2. When the methyl groups of tert-butyl bromide are
successively replaced by hydrogens, the rate of the
SN1reaction decreases progressively . This is opposite to
the order of reactivity exhibited by alkyl halides in SN2
reactions.
3. The reaction of an alkyl halide in which the halogen is
bonded to an asymmetric carbon forms two
stereoisomers: one with the same relative configuration at
the asymmetric carbon as the reacting alkyl halide, the
other with the inverted configuration.
27. Factors Affecting SN1 Reactions
The Leaving Group
The Solvent
Carbocation Rearrangements
28. The Leaving Group
two factors affect the rate of an reaction:
the ease with which the leaving group
dissociates from the carbon
the stability of the carbocation that is formed.
The weaker the base, the less tightly it is
bonded to the carbon and the easier it is to
break the carbon–halogen bond.
As a result, an alkyl iodide is the most
reactive and an alkyl fluoride is the least
reactive of the alkyl halides
29. The Solvent
The major effect of the solvent is on the rate of
nucleophilic substitution, not on what the
products are.
The higher the dielectric constant of solvent
(polar) , the better the medium is able to
support separated positively and negatively
charged species.
The rate of solvolysis of tert-butyl chloride
increases dramatically as the dielectric
constant of the solvent increases.
Aprotic solvents, lack OH groups and do not
solvate anions very strongly, leaving them
much more able to express their nucleophilic
character.
40. Reference
Advanced Organic Chemistry Reaction
Mechanisms Elsevier, 2002
ORGANIC CHEMISTRY Francis A.
Carey University of Virginia
MARCH’S ADVANCED ORGANIC
CHEMISTRY
REACTIONS, MECHANISMS, AND
STRUCTURE, SIXTH EDITION Michael
B. Smith, Jerry March
ORGANIC CHEMISTRY , PAULA
YURKANIS BRUICE, 4th edition
