The geometry of N-hydroxymethyl compounds. Part 2: Crystal structures of 1-(4-carbethoxyphenyl)-3-hydroxymethyl-3-methyltriazene, N-hydroxymethylpentamethylmelamine and N-hydroxymethylbenzamide.
Of the three N-hydroxymethyl compounds in the title, the first two have pronounced antineoplastic activity while the latter is biologically inactive. Crystals of the triazene have monoclinic symmetry with a = 8.540(1), b = 6.346(4), c = 22.460(5)A, beta = 98.75(2) degrees, and space group P21/c. The melamine forms disordered crystals of orthorhombic symmetry with a = 11.957(3), b = 17.267(3), c = 5.769(3)A. Of the symmetry elements in the observed space group Pnma, a mirror plane bisects the average molecule, implying that the hydroxymethyl group has equal probability of lying either side of this plane. Crystals of the benzamide show orthorhombic symmetry with a = 10.045(6), b = 7.763(3), c = 19.409(8)A, and space group Pbca. All three compounds are intermediates along biochemical demethylation pathways. The observed N-CH2OH distances, which are 1.469(5), 1.452(4), and 1.438(4)A respectively for the three compounds, correlate with the stability of this bond as measured by half-life. It is suggested that the correct degree of lability is important for biological activity, short strong bonds being too unreactive and excessively long ones being too unstable.
D006585:Altretamine / Q000031:analogs & derivatives; D000970:Antineoplastic Agents; D001549:Benzamides; D008968:Molecular Conformation; D014226:Triazenes; D014227:Triazines
D000970:Antineoplastic Agents; D001549:Benzamides; D014226:Triazenes; D014227:Triazines; C024065:pentamethylmonomethylolmelamine; C037309:N-hydroxymethylbenzamide; C056957:1-(4-carbethoxyphenyl)-3-hydroxymethyl-3-methyltriazene; D006585:Altretamine