Heterocyclic compounds-II Nucleophilic ring opening reactions of aziridines Three Membered Heterocyclic Compounds with One Hetero Atom, Chemical Properties Mechanism, Ring-Opening Reactions, azacyclopropane, Aziridine has often been called azacyclopropane or more common derivative of a parent alkene, ethylenimine.

1. HETEROCYCLIC COMPOUNDS
Nucleophilic ring opening
reactions of aziridines
Mr. Harshad R. Sonawane

2. Three Membered Heterocyclic Compounds with One Hetero Atom
1. AZIRIDINES
 Aziridines are the dihydro derivatives of parent azirines.
 Aziridine is a saturated heterocyclic compound containing two carbons and one nitrogen atoms in a three-
membered ring.
 Aziridines, as a class are of interest as biological alkylating and anti-cancer agents.
AZIRIDINES

3.  Besides, aziridine and its derivatives are produced commercially and are employed in plastic, coating and in
the textile industries. The chemistry of these compounds has been extensively investigated in recent years.
 Aziridine has often been called azacyclopropane or more common derivative of a parent alkene,
ethylenimine. Its derivatives, for instance, compounds (2) and (3) are named N-methylpropylenimine and
cyclopentenimine, respectively. In the Chemical Abstracts, however, the name ethylenimine is used for the
parent compound while its derivatives are indexed as aziridine, i.e., structure (2) is also called 1, 2-
dimethylaziridine. and (3) 6-azabicyclo [3.1.0) hexane.
CH3
H3C

4. Aziridines and derivatives are potent pharmacological agents. The tox effects of aziridine itself causes irritation
of eyes, skin, and internal inflammation. Besides the ability of aziridine as an alkylating agent importance in
industry and biology and this property has resulted in an of industrial applications of aziridines. Certain
antibiotics and anti-cancer agents possess the aziridine ring.
Chemical Properties
One of the most important reactions of small ring compounds is the ring opening. These rings are strained and
relief of strain makes ring-opening more facile. The aziridine ring is readily opened in the presence of several
reagents to provide a wide variety of derivatives. The most readily cleaved bond is between carbon and nitrogen.
1. Ring-Opening Reactions : The earlier methods for the preparation of ethylenimine included ring closure of a
β-halogenated alkylamine in the presence of a base. This reaction could, however, be reversed in the presence of a
mineral acid. Aziridine, thus yields β -chloroethylamine hydrochloride on treatment with HCl, equation (2.3) by
C-N bond cleavage.
HCl
NaOH
β -chloroethylamine
Aziridine

5. Aziridine
β -chloroethylamine
The reaction is first order and the mechanism involves an initial protonation of the ring nitrogen atom followed
by nucleophilic attack by the halide ion in a rate-limiting step.

6.  2-Phenylaziridine similarly forms the corresponding salt, as shown in following reaction-
C6H5
HCl
2-Phenylaziridine
 Acid chloride similarly opens the ring to an acetamide derivative N (2-chloroethyl) acetamide, as shown in
following reaction-
Aziridine
Aziridine

7.  Ring opening of an aziridine is also affected by nucleophilic reagents like water, alcohols and amines. With
water, aziridine yields β -hydroxyethylamine, as shown in following reaction-
Aziridine
β -hydroxyethylamine
 Ring opening also takes place with sodiomalonic ester leading to 3carbo-ethoxypyrrolidinone as the final
product.
Aziridine sodiomalonic ester

8.  Protonated aziridines or aziridinium salts are exceptionally reactive to nucleophilic attack because of the
release of strain energy inherent in a small ring. These reactions also proceed with extensive, if not complete
inversion of configuration at the site of attack. When unsymmetrical are involved ring opening can occur in
either of two directions. the nucleophile tends to attack the less hindered carbon atom with the result that
ring opening in one direction is predominant. The ratio of the products is however, affected by the nature of
solvent and reagents. Most aziridines which undergo direct nucleophilic ring opening carry electron-
withdrawing groups at the nitrogen atom. Those which do not bear such groups require vigorous conditions.