Nitrogen nonbasic

In contrast with amines, amides (RCONH ) are nonbasic. Amides don t undergo substantial protonation by aqueous acids, and they are poor nucleophiles. The main reason for this difference in basicity between amines and amides is that an amide is stabilized by delocalization of the nitrogen lone-pair electrons through orbital overlap with the carbonyl group. In resonance terms, amides are more stable and less reactive than amines because they are hybrids of two resonance forms. This amide resonance stabilization is lost when the nitrogen atom is protonated, so protonation is disfavored. Electrostatic potential maps show clearly the decreased electron density on the amide nitrogen. 

Indole has a nonbasic, pyrrole-like nitrogen and undergoes electrophilic substitution more easily than benzene. Substitution occurs at C3 of the electron-rich pyrrole ring, rather than on the benzene ring. 

Purine has three basic, pyridine-like nitrogens with lone-pair electrons in sp2 orbitals in the plane of the ring. The remaining purine nitrogen is nonbasic and pyrrole-like, with its lone-pair electrons as part of the aromatic i- electron system. 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

Palladium-catalyzed substitution can also be applied to nonbasic nitrogen heterocycles, such as indoles, in the absence of strong bases. 

Recently, Vayner and coworkers [239] have revisited the model proposed by Augustine et al. [34] which is based on the assumption that the QN can make a nucleophilic attack to an activated carbonyl. According to this model the two possible zwitterionic intermediates that can thus be formed have different energies, which leads to the selective formation of one of the two intermediates, and, therefore, to e.s. after hydrogenolysis by surface hydrogen. This model nevertheless does not explain the e.d. of nonbasic modifiers, such as the one reported by Marinas and coworkers [240], which have no quinuclidine moiety and no nitrogen atom, and thus no possibility to form zwitterionic intermediates. Furthermore, in situ spectroscopic evidence for hydrogen bond formation between the quinuclidine moiety of cinchonidine and the ketopantolactone has been provided recently [241], which supports the hypothesis of the role of weak bond formation rather than the formation of intermediates such as those proposed by Vayner and coworkers. 

In Sect. 7.3 and 7.4, we have emphasized that an amino group in an ester molecule contributes to increased water solubility and may, in some cases, facilitate enzymatic hydrolysis. In the present section, this argument is further illustrated and is extended to esters containing nonbasic nitrogenated pro-moieties, e.g., amidoalkyl or carbamoylalkyl substituents. Substituents liable to undergo fragmentation (i.e., pro-moieties that will break down during hydrolysis) will be discussed separately in Sect. 8.3. 

The other nitrogen compounds which are nonbasic, and are not extracted from hydrocarbons by dilute acid, have not been investigated in detail, though there are indications that they contain pyrroles. In addition, it is possible that some part of the nitrogen in this material is present in the form of amides, derived from primary or secondary amines and petroleum acids. 

Rearrangement of N-nitrosoamides. N-Nitrosamides (1), prepared by acetylation of primary amines followed by nitrosation, are known to decompose in nonpolar solvents at 80-100° to form alkyl acetates with elimination of nitrogen.9 The presumed diazoalkane intermediate (a) can be trapped as a rhodium carbene (b), which undergoes rearrangement to an alkene (equation I). The overall result is a mild, nonbasic version of the classical Hofmann degradation of amines. 

Basic nitrogen levels were measured by titration with perchloric acid in acetic acid (2). The acid titrant was standardized by titrating standard pyridine samples. Nonbasic nitrogen was calculated as the difference between total and basic nitrogen. 

Thus, the most likely survivors of fuel-rich, first-stage pyrolysis are unsubstituted and oxygen substituted aromatics and nonbasic nitrogen compounds. These are the precursors to soot and N0x formation during oxygen-rich, second-stage combustion. 

I Practice spotting basic and nonbasic I nitrogen atoms. Most nonbasic (pyrrole-like) nitrogens have three single bonds, and a lone pair in a I p orbital. Most basic (pyridine-like)... 

Show which of the nitrogen atoms in purine are basic, and which one is not basic. For the nonbasic nitrogen, explain why its nonbonding electrons are not easily available to become protonated. 

Methylation of normacrorine with dimethyl sulfate gave a 2 1 mixture of 116 and 117. On the basis of the negative inductive effect of the quinolyl substituent on the imidazole ring, one would expect on methylation in nonbasic medium isomacrorine to be the major product. The fact that, contrary to this expectation the main product is macrorine, can be explained by assuming a shielding of the most reactive imidazole nitrogen (N") by the quinolyl substitutent. 

All compounds that behave as narcotic analgesics characterized by the usual criteria contain a basic nitrogen center that either forms parts of an alicyclic ring system, as in morphine and pethidine, or terminates an acyclic chain, as in methadone, etonitazene, and the enkephalins. Nonbasic compounds of high activity in antinociceptive tests invariably fail to satisfy criteria for narcotic analgesics, such as reversal of effects by naloxone or nalorphine or evidence of binding to opioid receptors recent examples are the barbiturate... 

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