Page 173 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

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Heterocyclic Chemistry 329

anomeric effect). The anomeric effect is a guiding princi- Again, this nucleophilic behavior is easier when Z carries
ple in predicting the conformation of numerous carbohy- a negative charge.
drates. 3. The tendency of heterocycles to revert to their initial
degree of unsaturation if disturbed. Usually this means
HO
O
HO rearomatization.
HO
OH
H O
O
O
OH B. Nucleophilic Attack
sucrose HO
OH
Electron displacement toward the nitrogen atom often al-
lows nucleophilic reagents to attack alpha to a nitrogen
Sucrose (“sugar”) is an important example of these
heterocycle, such as in the Chichibabin reaction, in which
stereoelectronic effects. There is little doubt that confor-
alkali-metal amides induce amination.
mation is crucial to the function of many heterocycles
found in nature. X + _ HX
H H
N α _ Nu N _ Nu N Nu N Nu
nucleophilic addition-elimination at Cα of pyridine
III. CHEMICAL PROPERTIES
This type of reactivity is observed in benzenoid chem-
istry only when electron-withdrawing substituents are
A. Chemical Reactivity
present. However, a powerful nucleophile is needed to
All chemical reactions involve the making and breaking form appreciable quantities of the anionic nitrogen spe-
of a bond or bonds. For each bond broken, one new one is cies, which is of high energy, having been formed by
made. A bond can be formed or broken in a reaction step dearomatization of the initial heterocycle. In the case of
that is either (1) ionic, (2) free radical, or (3) electrocyclic. heterocyclic cations, nucleophilic attack is much easier,
Ionic mechanisms involve the transfer of two electrons chiefly because of the resulting neutralization of opposite
(depicted by a curved arrow) from either a lone pair or a charges.
multiple bond to another atom:
CH=CH-CH=CHNu
+ _ N + N N
A B A B
_ H Nu
+ _ Nu
D A B D A B nucleophilic attack resulting in ring opening
In many cases subsequent ring-closure occurs, to give
In a free-radical step, each atom contributes one electron
a new heterocyclic ring. In certain cases, such as the
(depicted by one single-headed arrow) to form a new bond:
Dimroth rearrangement of N-alkylated (or arylated) het-
erocycles to the corresponding alkylamine (or arylamine)
A B A B
heterocycles, the nature of the heterocyclic ring is not al-
In electrocyclic reactions, several bonds are formed and tered.
broken as part of a ring: N NaOH N
+
CHO CHO N NH 2 N NHMe
Me I _
Dimroth rearrangement
In heterocyclic chemistry, three patterns of reactivity C. Electrophilic Attack
are especially important: Electrophilic attack of pi-deficient heterocycles such as
1. The ability of a multiply bonded heteroatom to accept pyridine usually requires forcing conditions. Thus, nitra-
electrons at the site alpha to the heteroatom (Z): tion of pyridine at 300 C yields 3-nitropyridine in only
◦
poor yield.
Nu C Z or Nu C Z +
NO 2
300 °C
+ H 2 SO 4 /KNO 3 /SO 3
The attack is easier when Z carries a positive charge.
N N
2. The ability of a heteroatom attached to multiply
bonded carbon to donate a pair of electrons: As with nucleophilic attack, the site of electrophilic
attack can be rationalized, and is often predicted, by con-
C C or C C
Z _ Z sidering the relative stability of the structure formed prior