Basic strength amides

The choice of these derivatives, namely, those formed from amines of moderate strength, appears to be the best compromise for the synthesis to be effective. Although the susceptibility of phosphor-amidates to attack by nucleophiles increases with enhancement of the basic strength of the parent amine,279 280 the reverse trend is observed for the yields of nucleoside 5 -phosphoramidates when they are prepared from nucleoside 5 -phosphates by condensation with the appropriate amines through the action of N,N -dicyclohexylcarbodi-imide.279... 

Electronegativity influences the basic strength of the compound. If we compare the fluoride ion, hydroxide ion, amide ion and the methyl carbanion, then the order of basicity is as shown in the following figure ... 

The use of tertiary amines, amides, ethers, and thioethers also gives this kind of adduct. Because the stability of the complex varies directly with the basic strength of the ligand, it is found that the reactivity (which is determined by the ease with which sulfur trioxide is released from the complex) is inversely related to the stability of the complex and hence the basic strength of the ligand. It is found that the typical reactions of sulfur trioxide (e.g., sulfonation, sulfation, and sulfamation) are also reactions of the sulfur trioxide adducts, but coordination moderates the reactivity of the sulfur trioxide and usually makes it easier to control the reaction. 

In addition to the determination of total base, it is also possible to titrate mixtures. This can be done in two ways. One is to titrate mixtures based on the type of amines present. For example, one can distinguish between primary, secondary, and tertiary amines. This is done simply. Acetylate the primary and secondary amines in the mixture with acetic anhydride. They are converted to amides which are only weakly basic. Tertiary amines are not affected and titrate very well. A further differentiation can be made, however. The primary amine can be reacted with salicyl aldehyde to form a Schiff base. The secondary and tertiary amines are unaffected as far as basic strength is concerned, so that one can titrate the sum of secondary and tertiary amines. By these two titrations plus a determination of total amine, one can resolve the mixture. This approach works well for aliphatic amines, but not for aromatic amines. 

In some tertiary amines the proximity of electron withdrawing groups to the amine has an effect on basic strength. Thus diethazine has a pKa of 9.1 while lidocaine has a pKa of 7.9 (Fig. 3.8). In lidocaine the electron withdrawing amide group, separated by just one CH2 group from the amine, has a base weakening effect. 

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