STUDIES ON SYNTHESIS OF THE ANTIBACTERIAL AGENT NM441 .2. SELECTION OF A SUITABLE BASE FOR ALKYLATION OF 1-SUBSTITUTED PIPERAZINE WITH 4-(BROMOMETHYL)-5-METHYL-1,3-DIOXOL-2-ONE
T. Fuji et al., STUDIES ON SYNTHESIS OF THE ANTIBACTERIAL AGENT NM441 .2. SELECTION OF A SUITABLE BASE FOR ALKYLATION OF 1-SUBSTITUTED PIPERAZINE WITH 4-(BROMOMETHYL)-5-METHYL-1,3-DIOXOL-2-ONE, Chemical and Pharmaceutical Bulletin, 43(11), 1995, pp. 1872-1877
Diisopropylamine (DIPA), N,N-diisopropylethylamine (DIPEA), tributylam
ine (TNBA) and 7-(1-piperazinyl)-4-quinolone-3-carboxylic acid (2) wer
e titrated in water-dimethylformamide (DMF) mixtures containing 45-98%
DMF, Apparent pK(a) values in anhydrous DMF (pK(DMF)) were calculated
by extrapolation from the variation in the half-neutralization pH val
ues in aqueous DMF, The validity of the relative basicity derived from
the pK(DMF)s was confirmed by examination of the kinetics of esterifi
cation of a derivative of 2 with 4-(bromomethyl)-5-methyl-1,3-dioxol-2
-one (DMDO-Br). Relative basicities in DMF were: the carboxylate anion
of 2 much greater than DIPA > DIPEA > TNBA > the amino group in the p
iperazinyl part of 2, This order is clearly different from that observ
ed in water, We concluded that DIPEA is a suitable agent to suppress t
he undesired esterification during the reaction to mask the amino grou
p of 2 with a DMDO group, because it does not remove a proton from the
carboxyl group, but only from the protonated amino group.