Internal hydrogen bridging

Many papers exist about these relations for external hydrogen bridges. For internal hydrogen bridges, however, few data are known. 

The 9-formyl- and 9-benzoyltetrahydro-47/-pyrido[l,2-a]pyrimidin-4-ones derivatives exist predominantly as the 1,6,7,8-tetrahydro tautomer stabilized by an internal hydrogen bridge between N(l) and the 9-carbonyl group [83JCS(P2)1153 85JHC593]. 

In some cases the observed alkylation on N-4 does not lessen the validity of the generalization that suggests preference for N-1. Thus 3-phenyl-5-ureido-1,2,4-triazole (55) is methylated or benzylated to give (56 Scheme 20) because the internal hydrogen bridge preempts the favoured N-1 site. 

One example of the relevance of this in pharmaceutical chemistry are the two isomers 2-fluoro (2-F-NE) and 6-fluoronorepinephrine (6-F-NE) [21]. The modes of binding of these two different fluorinated isomers to their receptor are, unexpectedly, fundamentally different - 6-F-NE has agonistic a-adrenergic activity whereas 2-F-NE acts as a /i-agonist. This can be explained by the stabilization of two different preferred conformations by internal hydrogen bridges between the aliphatic hydroxy group and the aromatic fluorine (Scheme 4.15). 

Fig. 14 Bisignate CD-curves within the a-band of 3 related oxygensubstituted decahydrophenanthrenes, and CD of a related glycol allowing internal hydrogen bridging.

All the known annulenones are either polyenynones (dehydroannulenones), often with fused cyclohexene rings, or have pairs of internal hydrogens replaced by monatomic bridges. They will be discussed in order of increasing ring size. 

In many cases such as in 0-chlorophenol where relatively weak intramolecular hydrogen bridges are formed, the two bands are present together the position of the equilibrium between the free and the internally banded form can be calculated from the intensities. 

As early as 1940 the American chemist F. Stitt demonstrated that in B2H0 the barrier hindering the internal rotation about the hypothetical B—B bond is much higher as compared to ethane. Then some more experimental data appeared to promote the hydrogen bridge structure. Dilthey s model was again taken up in the publications by B. V. Nekrasov, Ya. K. Syrkin, M. E. Dyatkina in the USSR, and some foreign chemists. 

The [12]annulene 124 has been prepared. In solution, 124 undergoes rapid conformational mobility (as do many other annulenes), and above — 150°C in this par-tiuclar case, all protons are magnetically equivalent. However, at — 170°C the mobility is greatly slowed and the three inner protons are found at 5 while the nine outer protons are at 6 8. Interaction of the internal hydrogens in annulene 124 leads to nonplanarity. Above —50°C, 124 is unstable and rearranges to 125. Several bridged... 

Another C10 perimeter which becomes feasible with suitable bridging is the structure 29 possesssing three trans double bonds. In this case the unfavourable steric interaction of the three internal hydrogen atoms... 

Figure 40 Gas storage in coordination polymers, (a) Chemical structures of the dicopper(II) paddlewheel secondary building block and 5,5 -(9,10-an racene yl)diisophthalate tetra-anion in the structure of the [/xg-5,5 -(9,10-anthracenediyl)diisophthalato]-diaqua-dicopper(n) dimethylformamide solvate, and (b) representation of the honeycomb array with internal orthogonal bridges. The solvent molecules are not shown and the water-bound hydrogen atoms were not located in the original study.

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