Tricyclic orthoamide

Very unusual reactivity has been observed (82-84) with the tricyclic orthoamides 122 and 123. This can be readily explained on the basis of the stereoelectronic effects due to the three nitrogen electron pairs. 

Although 1,4,7-triazacyclononane was first incorporated into linked macrocyclic systems around three decades ago [7], it was only in 1997 that the corresponding three-ring analogue 1 was synthesised and investigated. The synthesis of 1 [8] (Scheme 1) proceeds from the tricyclic orthoamide derivative of 1,4,7-triazacyclononane 2 [9] and involves reaction with l,3,5-tris(bromomethyl)benzene in acetonitrile in a 3 1 molar ratio followed by base hydrolytic work-up of the product. The addition of excess HBr to the reaction mixture led to isolation of 1 as its nonahydrobromide salt in 76% yield. 

Scheme 10.18. Monoalkylation of a tricyclic orthoamide derived from 1,4,7-triazacyclononane[81].

The contrasting behaviour of the tricyclic orthoamides [44] and [45] towards triphenylcarbenium tetrafluoroborate has also been rationalized in terms of the necessity of adduct formation in the removal of the tertiary hydrogen (Atkins, 1980 Erhardt and Wuest, 1980). The dominant con-former of [44] has C3v symmetry, so that the central C—H is antiperi-planar with respect to all three nitrogen lone pairs. This hydrogen shows... 

Seiler P, Weisman GR, Glendening ED, Weinhold F, Johnson VB, Dunitz JD (1987) Observation of an eclipsed Csp3-CH3 bond in a tricyclic orthoamide Experimental and theoretical evidence for C-H- O hydrogen bonds. Angew Chem Int Ed Engl 26 1175-1177... 

Another interesting example for a C-H -OH2 hydrogen bond is provided by the X-ray crystal structure reported for the trihydrate of the tricyclic orthoamide shown below [467] ... 

Figure 12.38 The effect of the adjacent lone pairs on the axial and equatorial 7ch vsJues in 1,3-di-tert-butyl-5-methyl-l, 3-diazacyclohexane and on the Jch value for the central C-H bond in rigid tricyclic orthoamides.

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