Nitrogen Atom Reactions

Kinetics of Oxygen and Nitrogen Atom Reactions. The products of the photolysis of N20 are mainly nitrogen, oxygen, and nitric oxide.76 76 It is, therefore, necessary to consider reactions of atoms with N20 and with these products. The known rates of reaction of oxygen and nitrogen atoms with these molecules are listed in Table X. 

N-Methylation of pyridine-type nitrogen atoms (reaction 4, Fig. 13.15) seems to be of greater in vivo pharmacological significance than reactions 2 and 3 for two reasons. First, the resulting metabolites, being quaternary amines, are more stable than tertiary or secondary amines toward N-demethylation. And second these metabolites are also more polar... 

Nitrogen atom reactions with various olefins... 

This ligand polarization favors electrophilic attack on the terminal nitrogen atom. Reactions that activate dinitrogen are of interest as the basis for the fixation of nitrogen as ammonia. 

In the case of the ammonia-oxygen flame the addition of nitrogen atom reactions to the system brings in the possibility of a rapid bimolecular recombination step which reduces the number of free valencies (Sugden, 1965b). 

The strongly electronegative (p. 49) chlorine atom becomes a chloride ion, the proton accepting the electron pair donated by the nitrogen atom. A similar reaction occurs when ammonia is passed into water, but to a much lesser extent as oxygen in water is a poorer donor of the electron pair ... 

Thus, the values calculated for effective polarizability at the nitrogen atom for a series of 49 amines carrying only alkyl groups was correlated directly with their proton affinities, a reaction that introduces a positive charge on the nitrogen atom by protonation (Figure 7-7) [40. ... 

Figure 10.3-40. The rating for the disconnection strategy carbon-heteroatom bonds is illustrated, Please focus on the nitrogen atom of the tertiary amino group. It is surrounded by three strategic bonds with different values. The low value of 9 for one ofthese bonds arises because this bond leads to a chiral center. Since its formation requires a stereospecific reaction the strategic weight of this bond has been devalued. In contrast to that, the value of the bond connecting the exocyclic rest has been increased to 85, which may be compared with its basic value as an amine bond.

In spite of the diverse nature of alkaloid structures, two structural units, i.e. fused pyrrolidine and piperidine rings in different oxidation states, appear as rather common denominators. We therefore chose to give several examples for four types of synthetic reactions which have frequently been used in alkaloid total synthesis and which provide generally useful routes to polycyclic compounds with five- or six-membered rings containing one nitrogen atom. These are ... 

The nucleophilicity of the nitrogen atom survives in many different functional groups, although its basicity may be lost. Reactions of non-basic, but nucleophilic urea nitrogens provide, for example, an easy entry to sleeping-pills (barbiturates) as well as to stimulants (caffeine). The nitrogen atoms of imidazoles and indole anions are also nucleophilic and the NH protons can be easily substituted. 

Other interesting regioselective reactions are carried out within the synthesis of nitrofurantoin. Benzaidehyde semicarbazone substitutes chlorine in chloroacetic ester with the most nucleophilic hydrazone nitrogen atom. Transamidation of the ester occurs with the di-protic outer nitrogen atom. Only one nucleophilic nitrogen atom remains in the cyclization product and reacts exclusively with carbonyl compounds. 

Introduction of substituents on the carbocyclic ring relies primarily on electrophilic substitution and on organometallic reactions. The former reactions are not under strong regiochcmical control. The nitrogen atom can stabilize any of the C-nng o-complexes and both pyrrole and benzo ring substituents can influence the substitution pattern, so that the position of substitution tends to be dependent on the specific substitution pattern (Scheme 14.1). 

When the substituent on the nitrogen atom is -CH-C-R, R = H, Me, Rj = Ph. Me. two types of reactions can occur, according to the nature of the medium in which the base is allowed to react ... 

The interesting reactions where a free mercapto group is linked to the nitrogen atom of the thiazole (63), after the cleavage of a fused ring, is another illustration of the additive properties of the carbocation (Scheme 40). 

The quatemization of the nitrogen atom of the thiazole ring (the Menschutkin s reaction) by alkyl halide or methyl tosylate can be used to measure the reactivity of this atom and thus to evaluate steric and electronic effects of ring substituents. 

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