Aliphatic and Aromatic Nitrogen Compounds

This chapter covers both aliphatic and aromatic compounds that contain one or more nitrogen atoms in their structures. Only a small number of the nitrogen-containing compounds that could be considered will be reviewed here mainly based on their uses in industry. This is an update of a previous chapter and for each chemical, the first sentence will tell the reader whether there has been significant new information published in the literature and included or whether there has been little or no new information available for update and inclusion. Three-membered rings discussed are ethyleneimine, propyleneimine, and, one polyfunctional derivative, triethylenemelamine. Toxicologists, chemists, and biologists have always been interested in ethyleneimine and its derivatives because they are reactive, are useful at relatively low doses, and are moderately to highly toxic. Ethyleneimines are classic alkylating agents and have toxicological effects similar to nitrogen mustards. Monofunctional derivatives of ethyleneimine are less potent in producing the characteristic toxicity of the group than the derivatives that have two or more ethyleneimine groups. Finally, polymers of ethyleneimine and its derivatives have shown a relatively low order of toxicity. Six simple nitrogen mustards (β-chloroethylamines) are also covered in this chapter. They are all tertiary amines in which the halogen atom and the amine portion have reactivities similar to the alkyl halides and alkyl amines. They have no significant industrial uses in the United States, but they are used in medicine as “antineoplastic agents” and in treating some nonmalignant diseases. Representative nitrogen-containing chemicals that have five-membered rings (pyrrolidine, N-methyl-2-pyrrolidinone) and six-membered rings (piperidine, piperazine, morpholine, and hexamethylenetetramine) are also discussed in this chapter in some detail. Several representative aromatic nitrogen compounds are covered—pyrrole, aminotriazole, N-sulfenyl phthalimide fungicides, benzimidazole fungicides, and 1-H-benzotriazole. The data presented for compounds of this class that are used in agriculture include toxicology studies that have been published in the open literature as well as those available through company files to support governmental registration. In some cases, the high toxicity of the agent has been considered and is the reason for its inclusion here, rather than usage volume or industrial importance. Further, very little pharmacological information is presented because this is adequately covered in the pharmacological literature. We have tried to minimize hypotheses regarding the mechanism of action not because it is unimportant, but because the biochemistries are often very detailed, are almost always fairly speculative, and are presented comprehensively in other texts. Likewise, we resisted the temptation to employ structure–activity relationships because, although the database is very thorough for some chemicals, it did not contain enough analogous chemicals with known, comparable toxicity profiles. Keywords: aliphatic nitrogen compounds; aromatic nitrogen compounds; ethyleneimines; fungicides; mutagenicity