Nitrogen functional groups

Refer to previous sections for amides, lactams, carbamates, and imides. 

1 Amines. Most primary, secondary, and tertiary amines have pA values in the range of 7.5-11.5. Most aryl amines have pA values in the range of 4-6. The protonation state of amines is critical to an understanding of the degradation chemistry. Primary, secondary, and tertiary amines are nucleophilic and will react with electrophiles. Unprotonated amines are more easily oxidized and more volatile. 

Meropenem, a secondary amine, reacts with bicarbonate to reversibly form a CO2 adduct that exists in both the solid powder drug product and reconstituted solution [10]. 

Formaldehyde (HCOH) is a common impurity found from packaging material, resulting from reaction between carbohydrates and excipients. Since formaldehyde is a carbonyl, an API containing an amine is prone to reaction with this functionality (refer to Section A15.1.2.2). 

2 Imines and Enamines. Primary amines react with aldehydes and ketones to form the corresponding A-alkyl- or A-aryl-substituted imines (R— CO—R + R —NH2 R—C=(NR )—R + H2O). Imine formation is a 

---

Intramolecular nucleophilic additions by nitrogen functional groups onto pendant alkynes and allenes represent an important class of type la approaches to functionalized pyrroles. A platinum-catalyzed (PtCl4) cyclization of homopropargyl azides provided an entry to 2,5-disubstituted pyrroles and 4,5,6,7-tetrahydroindoles (fused pyrroles) <06OL5349>. 

But due to the importance of nitrogen functional groups, the addition reactions of selenium electrophiles to alkenes using nitrogen nucleophiles represent another synthetically relevant process. Nitriles have been used as versatile... 

Due to the important role of nitrogen functional groups, the addition reactions of an electrophilic selenium reagent and a nitrogen nucleophile to a carbon-carbon double bond represent a synthetically relevant process with potential practical applications. Among the reactions of this type which have been described already, perhaps the most important contribution is represented by the Ritter-type amide synthesis described by Toshimitsu and Uemura [48a, 48b]. The addition of a phenylselenyl and of an acylamino group to a mono or a 1,2-disubstituted olefin was accomplished by treating the olefin with PhSeCl in acetonitrile and water in the presence of trifluoromethanesulfonic acid. 

The following review covers especially the synthesis of aminocyclopropanes it deals with compounds in which a NR R moiety (R R heteroatom) is directly bonded to the three-membered ring. Cyclopropanes with other nitrogen functional groups are not included. Literature was considered until the end of 1984 the text was supplemented in October 1985. A very short review on aminocyclopropane chemistry appeared in 1974 by Gibson and DePuy Wasserman and coworkers surveyed some aminocyclopropane compounds derived from cyclopropanones. ... 

Thermolysis of pyrazolines was also used for aminocyclopropane synthesis. The corresponding starting materials were obtained from diazomethane and an alkene bearing a suitable nitrogen functional group, e.g. an amido or azido moiety. 

Oxidations of nitrogen compounds include oxidation at nitrogen as well as oxidations at carbons carrying the nitrogen functional groups. 

Raymundo-Pinero, E., Cazorla-Amoros, D., and Linares-Solano, A. (2003). The role of different nitrogen functional groups on the removal of SO2 from flue gases by N-doped activated carbon powders and fibres. Carbon, 41, 1925-32. 

The performance of a catalyst depends on the availability of suitable active sites, capable of chemisorbing the reactants and forming surface intermediates of adequate strength. Oxygen and nitrogen functional groups, which can be incorporated into the carbon materials by a variety of methods, play an important role in this context. The pertinent literature is discussed in this chapter, with particular emphasis on cases in which the active sites have been properly identified and useful activity correlations established. 

Of the many nitrogen functional groups in xenobiotics, only secondary and tertiary acyclic, cyclic, and arylamines as well as hydroxylamines and hydrazines are oxidized by FMO and excreted in the urine (Fig. 10.17). The tertiary amines form stable amine oxides, and secondary amines are sequentially oxidized to hydroxylamines, nitrones, and a complex mixture of products. Secondary N-alkylarylamines can be N-oxygenated to reactive N-hydroxylated metabolites, which are responsible for the toxic, mutagenic, and... 

---