Page 178 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

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Encyclopedia of Physical Science and Technology EN007F-314 July 6, 2001 16:59

334 Heterocyclic Chemistry

2. Properties and Importance Epoxides (oxiranes) are frequently used as synthetic
intermediates and are usually prepared from alkenes by
The reactivity of three- and four-membered heterocycles
treatment with peracids or metal–hydroperoxide systems
is dominated by ring strain, which facilitates ring opening.
(see Section V.A.1 above). Epichlorohydrin has been used
Four-membered rings often cleave to two two-membered
to prepare glycerol commercially. The strain of the small
fragments. Cationic three- and four-membered rings un-
ring leads to ready attack of epoxides by a wide variety of
dergo nucleophilic attack when undergoing ring opening.
nucleophiles.
Propiolactone undergoes ring opening, with the product
being dependent on nucleophile and acidity of the reac- OH
O
tion medium. Cl NaOH HO OH
O O O epichlorohydrin glycerol
A B
HO Nu A Nu OH
O _
B Nu O
RMgX
HO
ring opening reactions R
Anions of small heterocycles are uncommon. Extrusion
HO
of small gaseous fragments (e.g., N 2 ,CO 2 ) is very com- O RNH 2
mon for small, neutral heterocycles. Cis–trans isomeriza- H H NHR
tions via 1,3-diradicals are often observed when three-
membered heterocycles are heated or irradiated. An useful procedure for inverting of alkene geometry
involves stereospecific epoxidation and ring opening.
H H
N ∆ N
H H H H H H
R R R R
H Me 3 SiK
H + O _ SiMe 3
O K
H H
N N
H R H R
R H R H RCO 3 H
cis-trans isomerization of aziridines
Ring valence isomerizations of small rings are known.
Ring expansion of vinyl heterocycles is well known. In
trans-3-hexene cis-3-hexene

NMe
Me Cl O OCONH 2
N H
N O H 2 N OCH 3
P N
valence isomerization of an aziridine N NH
O
Cl O
many reactions of this form, especially when a three-
cyclophosphamide mitomycin C
membered heterocycle reacts inter molecularly with an
olefin, the heterocycle acts as a 1,3-dipole, by a formal ring Azetidine, the four-membered analog of aziridine, is
opening. Other ring expansions include the formation of a colorless liquid, stable at room temperature and less
reactive than aziridine. Interest in the cyclic amide aze-
∆
N tidinone rose rapidly in 1943, when it was correctly sug-
N
H gested that penicillins contained this heterocyclic ring.
formation of pyrrole by ring expansion The fused azetidinone ring is the key to the reactivity of
the two related series of antibioties, the penicillins and the
indole from 3-phenyl-1-azirine. Such ring expansions are
cephalosporins.
typical of three- and four-membered heterocycles, chiefly
because of relief of ring strain. O
H H
Ph HN S
∆
N
N
N O
H COOH
3-phenyl-1-azirine indole benzylpenicillin