Rotation barrier amide

Figure 2-51. a) The rotational barrier in amides can only be explained by VB representation using two resonance structures, b) RAMSES accounts for the (albeit partial) conjugation between the carbonyl double bond and the lone pair on the nitrogen atom. 

Rotational barriers for bonds which have partly double bond character are significantly too low. This is especially a problem for the rotation around the C-N bond in amides, where values of 5-10 kcal/mol are obtained. A purely ad hoc fix has been made for amides by adding a force field rotational term to the C-N bond which raises the value to 20-25 kcal/mol, and brings it in line with experimental data. Similarly, the barrier for rotation around the central bond in butadiene is calculated to be only 0.5-2.0 kcal/mol, in contrast to the experimental value of 5.9 kcal/mol. 

Investigations of hydrogen bonding of several thioamides have been carried out by calculations and spectroscopy. Characterization, hydrolysis and cyclization of thioamides have been discussed by using the results of calculations and spectroscopy. Comparison of amides and thioamides has been investigated.81 86 Rotation barriers for a series of amides and thioamides have been calculated.87 93... 

Table 5.27. Methyl rotation barriers Ai+b for various H-bonded andprotonated acetamide X complexes (cf. Fig. 5.64), with comparison NRT bond orders bco and bcs and bond lengths Rco and Rq n of the amide moiety in each complex...

The intimate connection between methyl torsional stiffening and the variation in amide CO/CN bond orders is illustrated in Fig. 5.65. This plot shows that the methyl rotation barrier A /s,b varies roughly linearly with the difference Ab in CO/CN bond orders,... 

Figure 5.65 The dependence of the acetamide methyl-rotation barrier (AT ) on NRT bond-order differences in the amide group (Ab = bco - cn) for various H-bonded complexes of the pseudo-cA (occH(in) = 0°) rotamer (see Table 5.27).

Wiberg, K.B. (2000). Origin of the amide rotational barrier. In The Amide Linkage. Structural Significance in Chemistry, Biochemistry and Materials Science, Greenberg, A., Breneman, C.M. and Liebman, J.F. (eds), p. 33. John Wiley Sons, Inc., New York... 

Comparison of the Barriers to Rotation of Amides, Thioamides, and Selenoamides... 

In tolnene-rfg, below 217 K, the benzyl aromatic signal resolved into two and the ben-zylic protons became diastereotopic. The exchange process, which was characterized by 217 = 246 s and AG = 10.2 kcalmoU, is a complex process involving both rotation aronnd the O—N bond and inversion at nitrogen, bnt since barriers to the former process are small the barrier best reflects that for rotation away from the anomeric conformation (Fignre 13). The amide isomerization barrier is even lower and both energies are in accordance with theoretical calcnlations (10.7 and 7.7 kcalmoG, respectively, for A—O rotation and amide isomerism in A-chloro-A-methoxyformamide) . 

The conformational barriers in acyclic radicals are smaller than those in closed-shell acycles, with the barrier to rotation in the ethyl radical on the order of tenths of a kilocalorie per mole. The barriers increase for heteroatom-substituted radicals, such as the hydroxymethyl radical, which has a rotational barrier of 5 kcal/mol. Radicals that are conjugated with a n system, such as allyl, benzyl, and radicals adjacent to a carbonyl group, have barriers to rotation on the order of 10 kcal/mol. Such barriers can lead to rotational rate constants that are smaller than the rate constants of competing radical reactions, as was demonstrated with a-amide radicals, and this type of effect permits acyclic stereocontrol in some cases. "... 

A number of azabicyclic derivatives have also been investigated (7 ICC 1104) as model compounds to study the effect of increasing the nitrogen inversion barrier upon the amide rotational barrier. From the experimental results and simplified MO pictures of the inversion and rotational mechanism, the authors (71CC1104) conclude that changes in the amide rotational barrier do not necessarily correspond to enhancement of the nitrogen inversion barrier. 

The first synthesized concave bases, the concave pyridine bislactames 3 (Structures 1), possess two amide groups in each molecule. The rotational barrier for a carboxamide bond is ca. 75 kJ/mol [12b, 19]. Therefore at room temperature, E-and Z-forms are observed in the NMR spectra. Because each concave pyridine bislactame 3 contains two amide groups, diastereoisomeric conformers are observable (see Fig. 2). Structures 5 show the ZZ-, EZ- and -conformers for the concave pyridine 3c. 

The rotational barriers of A-nitroso-, A-formyl and A-(A,A-dimethylcarbamoyl)-azetidines, compared with those of analogous acyclic amides, suggest that amide conjugation is weaker when the nitrogen is part of an azetidine ring (87KGS912). 

Separate signals for N-alkyl groups syn or (Z) and anti or ( ) to the carbonyl oxygen are observed for N-N-dialkylamides (Table 4.35) [313-315] due to the amide resonance. But the rotational barrier of the CN partial double bond decreases with increasing size of the carboxylic acid residue R [315]. 

Another example where aromaticity plays an important role is the barrier to the rotation of amides (compound 18 is represented with N in the middle to indicate any azole) [31]. In classical amides, like dimethylformamide (15), the calculated barrier is 80.1-81.0 kJ mol1 (MP2/6-311++G ), which compares well with the experimental barriers of 91.2 (solution) and 85.8 kJ mol1 (gas-phase) [32], The cases of A-formylaziridine (16) and iV-formyl-2-azirine (17) are more complex due to the pyramidalization of the nitrogen atom and the presence of rotation and inversion barriers [32], The effect of the antiaromatic character of 2-azirine (four electrons) [18] on the barrier is difficult to assess due to changes in the ring strain. 

An understanding of the internal rotation about the amide bond is important because of its relevance to protein structure. Formamide is the simplest amide. The coplanarity and the remarkable rotational barrier about the C-N bond in formamide can be rationalized by resonance between the n electrons of the carbonyl group and the lone pair of the nitrogen atom [1, 50]. According to VB theory, the Jt electronic structure of formamide may be described by six resonance structures. 

Contribution from resonance structure 3, which contains a formal double bond between carbon and nitrogen, is considered to be primarily responsible for the coplanarity and the high rotational barrier about the amide bond [58], The introduction of resonance structure 3 also implies that there is significant charge-delocalization from the nitrogen lone pair to the carbonyl oxygen. 

This resonance representation correctly predicts a planar amide nitrogen atom that is sp2 hybridized to allow pi bonding with the carbonyl carbon atom. For example, formamide has a planar structure like an alkene. The C—N bond has partial double-bond character, with a rotational barrier of 75 kJ/mol (18 kcal/mol). 

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