Carbonyl group reaction with nitrogen bases

Tire nitrogen atom in the pyridine ring is planar and trigonal with the lone pair in the plane of the ring. This makes it an imine. Most of the imines you have met before (in Chapter 14, for example), have been unstable intermediates in carbonyl group reactions, but in pyridine we have a stable imine—stable because of its aromaticity. All imines are more weakly basic than saturated amines and pyridine is a weak base with a pK of 5.5. This means that the pyridinium ion as about as strong an acid as a carboxylic acid. 

The enrichment in nitrogen of humic substances extracted in EDA (Table 5) suggests that solvents containing this compound, or any other primary amine, would not be appropriate for use with humic substances. EDA readily reacts with carbonyl groups to form Schiff base structures. Such reactions are rapid when the protonated carbonyl group reacts with the nonpro-tonated amine. Thus the maximum reaction rate occurs when the product of the concentrations of the protonated carbonyl groups and free amines is maximum. The reaction continues, but at a rate which decreases in an exponential manner, as the pH is raised or lowered from the optimum value for the reaction. 

Both carbonyl groups of terephthaldehyde are reported to react with the exocyclic nitrogen of 2-aminothiazole yielding 1.4-phenylene bis(2-methyleneamino)thiazole. The same report describes the reactions of 2-amino-4-phenylthiazole with terephth aldehyde and salicylaldehyde as yielding 64 and 65, respectively (Scheme 45) (215), whose structures are based on ultraviolet and infrared spectra. 

De Bruin and van der Plas (79) also used hydroxylamine in an attempt to identify carbonyl groups. It is not stated whether this reagent was used as free base or as a salt. The considerable nitrogen uptake was very nearly the same as on reaction with ammonia in methanol. Perhaps ammonium salts had been formed in both reactions. The same authors found a pronounced reduction with TiClj which exceeded by far the extent of all other reactions. The TiClj reaction gave easily reproducible results. 

Several therapeutic agents are based on phthalazinone nuclei, in which the hydrazide carbonyl group persists in unmodified form. Reaction of keto-acid (69-1) with hydrazine leads to the phthalazinone (69-2). Alkylation of the hydrazide nitrogen with 2-(chloroethyl)-A-methylpyrrolidine (69-3) surprisingly leads to the incorporation of a seven-membered azepine ring rather than the expected ethylpyrroldine. This can be explained by keeping in mind that it is likely that the... 

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