The crystal and molecular structure of the antifolate drug trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine). A neutron diffraction study

1:1 Molecular complex of trimethoprim and sulfametrole

“…formation of the TMP cation, since the corresponding angle in unprotonated TMP is 115.5 ° (Koetzle & Williams, 1976).…”

2,4-Diaminopteridine monohydrate

“…These changes can be rationalized by invoking the resonance structures in which the exo-+ cyclic amino groups donate electrons to the ring, and the bond order at N(8) decreases. Both exocyclic C--N bonds are 0.015 (3)A shorter than those in the diaminopyrimidine derivative trimethoprim (Koetzle & Williams, 1976), presumably owing to the presence of two extra N atoms fused into the ring system. The pteridine ring atoms are coplanar within 0.04 (1)/k, but amino N atoms N(2) and N(4) are displaced by 0.10 (1) and 0.12 (1)/~,, respectively, to opposite sides of the ring.…”

“…Molecules associate efficiently ( (Koetzle & Williams, 1976). The other amino group finds a proton acceptor in the pyrazine moiety of another centrosymmetrically related molecule, forming an unusual cyclic dimer with N(4)...N(5) distance 3.066(3)A.…”

7-Benzyloxy-1,4-dihydro-6-methoxyisocoumarin

“…The dihydropyran ring is in the boat conformation (see Table 2); the asymmetry parameter C s (C 1) = 1.07 (Duax, Weeks & Rohrer, 1976) [115.2(1) °] (Sheldrick, Akrigg & Geddes, 198.0;Koetzle & Williams, 1976). The shortened distance C(7)-O(11) 1.367 (2)/k and angle C(7)-O(11)-C(12) 117.1 (1) ° are, perhaps, indicative of some sp 2 character of the atom O(11) (Durant, Bufkens, Lefeore, Evrard & Michel, 1985).…”