Pyramidal nitrogens

Adenine as an isolated molecule has no symmetry elements and therefore might mathematically be considered chiral however, as in the case of glycine (Section 1.2.1), this description is not useful in chemistry since the enantiomers differ only by inversion through the weakly pyramidal nitrogen atom of the amine functionality, the main body of the molecule being planar. The inversion corresponds to a low-frequency vibration and a low-energy barrier such that single enantiomers... 

Pyramidal nitrogen is favorable for slow inversion. In this case, two methyl groups in the SilV Bu fragment are nonequivalent, whereas two SiMej groups are, on the contrary, equivalent. However, any two identical substituents at the nitrogen atom become nonequivalent in the presence of the asymmetric center G attached to the C,C double bond. 

Both AMI calculations on A-acetoxy-A-methoxybenzamide38 and ab initio 6-31G calculations on A-formyloxy-A-methoxyformamide 405 45 predict a strongly pyramidal nitrogen. Its lowest energy conformation at HF/6-31G is depicted in Fig. 5a while structural data are provided in Table 1 together with that for A-methoxyformamide 41. 

While all strain effects in monoamines are basicity weakening, it is possible to find cases in di- and polyamines where strain is relieved upon protonation, leading to increased basicity. This phenomenon is observed in 1,4-diaminobutane derivatives where an almost linear N... H—(N+) hydrogen bond in the mono-protonated derivatives leads to a stable, seven-membered ring structure. Thus, for example, the measured PA of l,6-diazabicyclo[4.4.4]tetradecane (73) is 228.3 kcalmol-1, about 11 kcalmol-1 higher than its monoamine analog 75, despite the similar, inwardly pyramidalized, nitrogen conformation of both neutral amines. 

Such a substitution may involve substantial changes in the structure and disturb the cyclic electron delocalization. Thus, 1,4-dihydropyrazine (25), as judged from X-ray data on its N-substituted derivatives [83AG(E)171] as well as from the results of MNDO [84JMS( 109)277] and ab initio (6-31G) (88JOC2127) calculations, has a slightly bent boat structure with pyramidalized nitrogen atoms. 

Special cases of these involving transition states for rotation about single bonds, inversion of pyramidal nitrogen and phosphorus centers and ring inversion in cyclohexane, have been discussed in the previous chapter. The only difference is that these conformational processes are typically well described in terms of a simple motion, e.g., rotation about a single bond, whereas the motion involved in a chemical reaction is likely to be more complex. 

An alternative hypothesis for this preferential attack from the more hindered side has been presented and supported by calculations21. Thus, preferential exo solvation due to favorable electrostatic interaction between the lithium and the pyramidalized nitrogen blocks attack from this side. 

The stereochemistry of azacyclohexanes is complicated by the fact that there is a conformational change in the ring as well as inversion at the pyramidal nitrogen. Therefore it is difficult to say whether the axial-equatorial equilibrium of, for example, 1-methylazacyclohexane is achieved by ring inversion, or by nitrogen inversion, or both ... 

The enantiomeric forms 83a and 83b are related by the intermediate 84, in which rotation around both the N—M and the Si—N bonds may occur. Rotation around the Si—N bond is associated with an inversion at the pyramidal nitrogen atom. In a similar manner, in the chelates 46-48 the breaking of the O—M bond is accompanied by rotation around the respective bonds, and a very rapid transformation of one enantiomeric form (85a) into the other (85b) is observed [Eq. (35)] (65). 

Schurig, V., Biirkle, W., Zlatkis, A., and Poole C. F. (1979) Quantitative resolution of pyramidal nitrogen invertomers by complexation chromatography, Naturwissenschaften 66, 423. 

Inversion of the pyramidal nitrogen of azetidines is a major feature of these azaheterocycles. The Afor the inversion is at best only a few kcal (around lOkcalmol ) <1996CHEC-II(1B)507>. 

The electrostatic potential map for trimethylamine shows how the nonbonding electrons give rise to a red region (high negative potential) above the pyramidal nitrogen atom. 

If one of the ring junctions is a nitrogen atom, we might think that there is no question of stereochemistry because pyramidal nitrogen inverts rapidly. So it does, but if it is constrained in a small ring, it usually chooses one pyramidal conformation and sticks to it. The next case is rather like the last. 

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