W0232
Close H..H Contacts in
Derivatives of Antimycobacterial Amidrazones. C.H. Schwalbe, N.D.
Cox, D.L. Rathbone, K.J. Parker and N. Khan, Aston
Pharmacy School, Aston Univ., Birmingham B4 7ET, UK.
Our work on antimycobacterial
2-heteroarylcarboxyamidrazones of general structure (I) has recently been
extended to systems where a clash of hydrogen atoms can be expected, namely
positional isomers (class Ib) in the heteroaryl ring and derivatives (II)
bearing a hydrogen atom on N9.
The reasonably planar type (I)
molecules form sharply angled (ca. 100°) but unhindered N-H..N
interactions [1] from the amino group to the aryl N1 and N9 in the chain.
In class (Ib) C-H..H-N contacts are as low as 1.97 Å and always
less than the 2.40 Å expected from van der Waals radii. In (IIa,b,c) the
N-H..H-N clash between the amino group and N9 could be exacerbated by
electrostatic repulsion, but the H..H contacts are close:
Structure IIa IIb IIc(1)
IIc(2)
(N)H positions set by AFIX 1.98 1.89 1.78 1.79
Å
Freely refined with SHELXL97 1.84 1.94 2.18 2.30
Upon refinement IIa and IIb changed little, but the geometry
at N9 of both independent molecules of IIc became pyramidal with torsion angles
C7-N8-N9-H9 ca. ±60°. Ab initio molecular orbital
optimizations on IIb without its t-butyl group gave basis set dependent H..H
distances of 2.38 Å with 3-21G, 2.26 Å with 6-31G*, and (at present)
2.25 Å with 6-31G**.
[1] C.H. Schwalbe, D.C. Billington,
B. Gordon, D.L. Rathbone and P.R. Lowe (1998). J. Pharm. Pharmacol., 50(Suppl.),
245.
