N and C protonation

The C-protonation product 124, which may be chemically also obtained by N-protonation of the imines 122a and 122b, is lower in energy than 123, so that it is the thermodynamically favoured product. The calculated energy difference of 124 to the kinetically preferred 123 is 18.66 kcal mol-1 in the 6-31G basis. (The 6-31G value is 17.32 and the 3-21G value is 13.17 kcal mol-1, so that this difference clearly increases with improvement of basis sets.). 

The C-protonation energy of 115 of the type 118 in the 6-31G basis set is — 240.27 kcal mol-1 and the N-protonation energy of 122b related to 123 is —215.78 kcal mol-1. Both values are smaller than the 6-31G calculated value of —250.55 kcal mol-1 for -formamidine184 (137). For comparison, the 6-31G calculated protonation energy of methylamine184 is —228.20 kcal mol-1 and that for ammonia184 is —217.38 kcal mol-1. 

TABLE 8. Basis set dependence of calculated geometries of protonated vinylamine. N protonation = vinyl ammonium cation (123) C protonation = methyl iminium cation (124). Distances in A and angles in deg 

Nomenclature and numbering of atoms in molecules used for calculations in Tables 5 to 14 

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All this leads to the conclusion that the relative stabilities of the N- and C-protonated forms of enamines are not very different and that relatively minor structural differences or differences of medium favour one form over the other. 2-Alkyl substituents especially favour C-protonation (Hinman, 1968). They certainly greatly enhance the basicity of pyrroles which are C-protonated (see page 358). 

As noted in Sect. II, sym-tris(dialkylamino)benz ies interact with electrophilic reagents to generate triaminobenzenium ions (29). The ring hydrogens of these ions are listed in Table 17. The concurrence of the N- and C-protonation of triamino-benzenes is discussed in Sect. III.4. 

Nuclear Overhauser enhancement (NOE) spectroscopy has been used to measure the through-space interaction between protons at and the protons associated with the substituents at N (20). The method is also useful for distinguishing between isomers with different groups at and C. Reference 21 contains the chemical shifts and coupling constants of a considerable number of pyrazoles with substituents at N and C. NOE difference spectroscopy ( H) has been employed to differentiate between the two regioisomers [153076 5-0] (14) and [153076 6-1] (15) (22). N-nmr spectroscopy also has some utility in the field of pyrazoles and derivatives. 

Figure 4 Sequential assignment of the backbone atoms for the segment Pro-109 to Val-113 of inhibited sfSTR by 4-D HCANNH and 4-D HCA(CO)NNH. Four planes are shown from each spectrum. The assigned backbone atoms are indicated in (A). In (B) the upper four planes in solid lines are from the 4-D HCANNH and the lower four planes in dashed lines are from the 4-D HCA(CO)NNH. The chemical shifts for the four correlated nuclei in each case are shown. The correlations continue for the segment Pro-109 to Pro-129. As Pro lacks a protonated N, this residue serves as a "stop" signal. The correlation of 19 residues with Pro at the N- and C-terminal ends is unique for this segment in the sequence of sfSTR, therefore these backbone atoms are specifically assigned without having to further assign side chain atoms. (From Ref. 5.)...

These conclusions are reinforced by measurement of natural abundance 15N chemical shifts in piperidines and decahydroquinolines (77JA8406,78JA3882,78JA3889). Lack of correlation between 13C shifts of cyclohexanes and 1SN shifts of piperidines bearing the same methyl substituents are attributed to, among other factors, solvent effects and the difference between H-lone pair and H-H interactions. Protonation served to cancel these stereoelec-tronic effects. Correspondence between 1SN shifts in N- and C- methyl substituted piperidines and decahydroquinoline hydrochlorides and the analogous 13C values were, however, generally much closer than for saturated aliphatic amines. 

It has been shown experimentally that attack by strong nucleophiles also occurs regio-selectively at this C atom, stereo selectively from the face opposite to the metal [287]. Since the alkyl group a bonded to the metal is very carbanion-like, it is susceptible to protonation by acids, yielding an alkane. The overall reaction provides the mechanism for homogeneous hydrogenation of alkenes. It may be extended to hydrogenation of C=N and C=0 pi bonds. 

The characteristic structural features of two-coordinate low-valent germanium cation 276 are similar to those of the analogous Si cation 268 discussed above. The average C—N and C—C bond distances (1.348 A and 1.392 A, respectively) and the essentially planar ring indicate aromatic delocalization.691 In contrast, however, the y-CH proton (8 H 4.23) is more shielded. The aromatic substituents are perpendicular to the GeN2C3 plane. 

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