Nucleophilic Substitution Reactions
at the Saturated C Atom 2
2.1 Nucleophiles and
Electrophiles; Leaving Groups
Stated with some exaggeration, organic chemistry is comparatively simple to learn be-
B
cause most organic chemical reactions follow a single pattern. This pattern is
valence
nucleophile + product(s)
electron pair
electrophile
shift(s)
A nucleophile is a species that attacks the reaction partner by making a pair of
elec- trons available to it; it is thus an electron pair donor. An electrophile is a
species that reacts by accepting a pair of electrons from the reaction partner so that
it can be shared between them. An electrophile is thus an electron pair acceptor.
As electron pair donors, nucleophiles must either contain an electron pair that is Electrophiles and
easily available because it is nonbonding or they must contain a bonding electron Nucleophiles
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 neu-
tral species but not cations. In this book nucleophile is abbreviated as “Nu ,” re-
gardless of charge.
According to the definition, electrophiles are electron pair acceptors. They there-
fore contain either a deficiency in the valence electron shell of one of the atoms
they consist of or they are indeed valence-saturated but contain an atom from which
a bonding electron pair can be removed as part of a leaving group. Concomitantly
this atom accepts the electron pair of the nucleophile. Electrophiles are therefore,
as a rule, cations or neutral compounds but not anions. In this book electrophile is
abbreviated as “E ,” regardless of charge.
For most organic chemical reactions, the pattern just specified can thus be
written more briefly as follows:
Nu + E Nu E (+ by-products)
In this chapter we deal with nucleophilic substitution reactions at the saturated,
that is, the sp3-hybridized C atom (abbreviated “SN reactions”). In these reactions,
,alkyl groups are transferred to the nucleophiles. Organic electrophiles of this
type are re- ferred to as alkylating agents. They have the structure 1R3 n Hn2 Csp ¬X.
3
The group X is displaced by the nucleophile according to the equation
,44 2 Nucleophilic Substitution Reactions at the Saturated C Atom
k
Nu + Csp3 X Nu C sp3 + X
as X . Consequently, both the bound group X and the departing entity X are
called leaving groups. Some uncharged and a few positively charged three-
membered heterocycles also react as alkylating agents. Instead of simple alkyl
groups, they transfer alkyl groups with a heteroatom in the b position. The most
important hete- rocyclic alkylating agents of this type are the epoxides. When
there are no Brønsted or Lewis acids present, epoxides act as b-hydroxy
alkylating agents with respect to nucleophiles:
O k O aqueous
Nu + Nu Nu
workup
OH
Rx Rx Rx
According to this equation, the product is indeed produced by an SN reaction
be- cause the nucleophile displaces an oxyanion as a leaving group from the
attacked C atom. Nonetheless this oxyanion is still a part of the reaction product.
In this respect this reaction can also be considered to be an addition reaction. An
intermolecular ad- dition reaction is one that involves the combination of two
molecules to form one new molecule. An intramolecular addition reaction is one
that involves the combination of two moieties within a molecule to form one
new molecule.
2.2 Good and Poor Nucleophiles
Which nucleophiles can be alkylated rapidly and are thus called “good
B
nucleophiles”? Or, in other words, which nucleophiles have “high nucleophilicity”?
And which nucle- ophiles can be alkylated only slowly and are thus called “poor
nucleophiles”? Or, in other words, which nucleophiles have “low
nucleophilicity”? Or let us ask from the point of view of the alkylating agent:
Which alkylating agents react rapidly in SN re- actions and thus are “good
alkylating agents” (good electrophiles)? Which alkylating agents react slowly in
SN reactions and thus are “poor alkylating agents” (poor elec- trophiles)? As
emerges from these definitions, good and poor nucleophiles, high and low
nucleophilicity, good and poor alkylating agents, good and poor electrophiles, and
high and low electrophilicity are kinetically determined concepts.
Answers to all these questions are obtained via pairs of SN reactions, which are
car- ried out as competition experiments. In a competition experiment two
, reagents react simultaneously with one substrate (or two substrates react
simultaneously with one reagent). Two reaction products can then be produced.
The main product is the com- pound that results from the more reactive
(synonymous with “faster reacting”) reac- tion partner.
at the Saturated C Atom 2
2.1 Nucleophiles and
Electrophiles; Leaving Groups
Stated with some exaggeration, organic chemistry is comparatively simple to learn be-
B
cause most organic chemical reactions follow a single pattern. This pattern is
valence
nucleophile + product(s)
electron pair
electrophile
shift(s)
A nucleophile is a species that attacks the reaction partner by making a pair of
elec- trons available to it; it is thus an electron pair donor. An electrophile is a
species that reacts by accepting a pair of electrons from the reaction partner so that
it can be shared between them. An electrophile is thus an electron pair acceptor.
As electron pair donors, nucleophiles must either contain an electron pair that is Electrophiles and
easily available because it is nonbonding or they must contain a bonding electron Nucleophiles
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 neu-
tral species but not cations. In this book nucleophile is abbreviated as “Nu ,” re-
gardless of charge.
According to the definition, electrophiles are electron pair acceptors. They there-
fore contain either a deficiency in the valence electron shell of one of the atoms
they consist of or they are indeed valence-saturated but contain an atom from which
a bonding electron pair can be removed as part of a leaving group. Concomitantly
this atom accepts the electron pair of the nucleophile. Electrophiles are therefore,
as a rule, cations or neutral compounds but not anions. In this book electrophile is
abbreviated as “E ,” regardless of charge.
For most organic chemical reactions, the pattern just specified can thus be
written more briefly as follows:
Nu + E Nu E (+ by-products)
In this chapter we deal with nucleophilic substitution reactions at the saturated,
that is, the sp3-hybridized C atom (abbreviated “SN reactions”). In these reactions,
,alkyl groups are transferred to the nucleophiles. Organic electrophiles of this
type are re- ferred to as alkylating agents. They have the structure 1R3 n Hn2 Csp ¬X.
3
The group X is displaced by the nucleophile according to the equation
,44 2 Nucleophilic Substitution Reactions at the Saturated C Atom
k
Nu + Csp3 X Nu C sp3 + X
as X . Consequently, both the bound group X and the departing entity X are
called leaving groups. Some uncharged and a few positively charged three-
membered heterocycles also react as alkylating agents. Instead of simple alkyl
groups, they transfer alkyl groups with a heteroatom in the b position. The most
important hete- rocyclic alkylating agents of this type are the epoxides. When
there are no Brønsted or Lewis acids present, epoxides act as b-hydroxy
alkylating agents with respect to nucleophiles:
O k O aqueous
Nu + Nu Nu
workup
OH
Rx Rx Rx
According to this equation, the product is indeed produced by an SN reaction
be- cause the nucleophile displaces an oxyanion as a leaving group from the
attacked C atom. Nonetheless this oxyanion is still a part of the reaction product.
In this respect this reaction can also be considered to be an addition reaction. An
intermolecular ad- dition reaction is one that involves the combination of two
molecules to form one new molecule. An intramolecular addition reaction is one
that involves the combination of two moieties within a molecule to form one
new molecule.
2.2 Good and Poor Nucleophiles
Which nucleophiles can be alkylated rapidly and are thus called “good
B
nucleophiles”? Or, in other words, which nucleophiles have “high nucleophilicity”?
And which nucle- ophiles can be alkylated only slowly and are thus called “poor
nucleophiles”? Or, in other words, which nucleophiles have “low
nucleophilicity”? Or let us ask from the point of view of the alkylating agent:
Which alkylating agents react rapidly in SN re- actions and thus are “good
alkylating agents” (good electrophiles)? Which alkylating agents react slowly in
SN reactions and thus are “poor alkylating agents” (poor elec- trophiles)? As
emerges from these definitions, good and poor nucleophiles, high and low
nucleophilicity, good and poor alkylating agents, good and poor electrophiles, and
high and low electrophilicity are kinetically determined concepts.
Answers to all these questions are obtained via pairs of SN reactions, which are
car- ried out as competition experiments. In a competition experiment two
, reagents react simultaneously with one substrate (or two substrates react
simultaneously with one reagent). Two reaction products can then be produced.
The main product is the com- pound that results from the more reactive
(synonymous with “faster reacting”) reac- tion partner.
