Displacement nitrogen mustard

Nitrogen mustards such as 23 decompose to yield aziridinium ions 24 (Scheme 8.14). " As in the case of sulfur mustards, the reaction involves rate-limiting intramolecular displacement of p-chlorine by nitrogen. The resulting aziridinium ions... 

Very reactive nitrogen mustards and aziridine-containing molecules are usually too toxic for general therapeutic use, but find use in neoplastic disease. Benzodepa (182) is such an agent. Treatment of ethyl carbamate with phosphorous pentachloride leads to cyanate 180 which readily adds benzyl alcohol to produce carbamate 181. Displacement of the active... 

The nitrogen mustard compound mechlorethamine (Fig 6.10) was the first alkylating agent to be used (1942). The nitrogen atom is able to displace a chloride ion intra-molecularly to form the highly electrophilic aziridine ion. Alkylation of DNA can then take place. Since the process can be repeated, cross-linking between chains will occur. 

The mechanism of action of the nitrogen mustards (14) is depicted in Figure 42.1. In step 1, the lone pair of electrons on the un-ionized amino group conducts an intramolecular nucleophilic attack at the (3-carbon of the mustard, displacing chloride ion and forming the highly electrophilic aziridinium ion intermediate, a quaternary amine salt. The carbon atoms of this strained cyclic structure are highly electrophilic... 

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