Properties and Synthetic Utility of N-Substituted Benzotriazoles.

Carbohydrates as ligands: coordination equilibria and structure of the metal complexes

The rate constants for deprotonation of ethyl acetate by 3-substituted quinuclidines are correlated by β = 1.09 ± 0.05. The limits of kBH = 2−5 × 109 M-1 s-1 for the encounter-limited reaction of the simple oxygen ester enolate with protonated quinuclidine (pKBH = 11.5) were combined with kB = 2.4 × 10-5 M-1 s-1 for deprotonation of ethyl acetate by quinuclidine, to give pKaK = 25.6 ± 0.5 for ionization of ethyl acetate as a carbon acid in aqueous solution. A rate−equilibrium correlation for proton transfer from methyl and benzylic monocarbonyl compounds to hydroxide ion has been extended by 6 pK units in the thermodynamically unfavorable direction, and it is shown that the absence of curvature of this correlation is inconsistent with a constant Marcus intrinsic barrier for the enolization of simple carbonyl compounds.

Determination of the pKa of Ethyl Acetate: Brønsted Correlation for Deprotonation of a Simple Oxygen Ester in Aqueous Solution

6-[5-(4-Amidinophenyl)furan-2-yl]nicotinamidine (8a) was synthesized from 6-[5-(4-cyanophenyl)furan-2-yl]nicotinonitrile (4a), through the bis-O-acetoxyamidoxime followed by hydrogenation. Compound 4a was prepared via selective bromination of 6-(furan-2-yl)nicotinonitrile (2a) with N-bromosuccinimide, followed by Suzuki coupling with 4-cyanophenylboronic acid. In a similar way, diamidines 8b and 8c were prepared from the dicyano derivatives 4c and 4d, respectively. N-Methoxy-6-{5-[4-(N-methoxyamidino)phenyl]-furan-2-yl}-nicotinamidine (6a) was prepared via methylation of the respective diamidoxime 5a with dimethylsulfate. Prodrugs 6b and 6c were also prepared by methylation of the respective diamidoximes 5b and 5d. The symmetrical diamidines 14a,b were synthesized through the corresponding bis-O-acetoxyamidoxime followed by hydrogenation. The key compounds 11a,b were conveniently obtained by Stille coupling between 2,5-bis(tri-n-butylstannyl)furan and the corresponding heteroaryl halides. These compounds ...

Synthesis and antiprotozoal activity of aza-analogues of furamidine.

The syntheses of 12 new 2,5-bis[4-(N-alkylamidino)phenyl]furans are reported. The interaction of these dicationic furans with poly(dA-dT) and with the duplex oligomer d(CGCGAATTCGCG)2 was determine...

2,5-bis[4-(N-alkylamidino)phenyl]furans as anti-Pneumocystis carinii agents.

Absolute and relative electrophilicities of a carbonyl group and tertiary ammonium ions toward a simple enolate ion

The kinetic study of the aqueous reaction, between pH 10 and 14, of eight N-(hydroxymethyl)benzamide derivatives in water at 25 °C, I = 1.0 M (KCl), has been performed. In all cases, the reaction proceeds via a specific-base-catalyzed deprotonation of the hydroxyl group followed by rate-limiting breakdown of the alkoxide to form aldehyde and amidate (E1cB-like). Such a mechanism was supported by the lack of general buffer catalysis and the first-order dependence of the rate of reaction at low hydroxide concentrations and the transition to zero-order dependence on hydroxide at high concentration. A ρ-value of 0.67 was found for the Hammett correlation between the maximum rate for the hydroxide independent breakdown of the deprotonated carbinolamide (k1) and the substituent on the aromatic ring of the title compounds. Conversely, the substituents on the aromatic ring of the amide portion of the carbinolamide had only a small effect on the Ka of the hydroxyl group indicating that the amide group does not str...

Amidates as Leaving Groups: Structure/Reactivity Correlation of the Hydroxide-Dependent E1cB-like Breakdown of Carbinolamides in Aqueous Solution

Kinetic dependence of the aqueous reaction of N-(hydroxymethyl)benzamide derivatives upon addition of electron-withdrawing groups.

Nucleofugality of the benzotriazole group in solvolysis

The induction of strain in carbocycles, thereby increasing the amount of s-character in the C−H bonds and the acidity of these protons, has been probed with regard to its effect on the rate constan...

Determination of the pKa of cyclobutanone: Brønsted correlation of the general base-catalyzed enolization in aqueous solution and the effect of ring strain.

Richard W. Nagorski

Papers

Absolute and relative electrophilicities of a carbonyl group and tertiary ammonium ions toward a simple enolate ion

Amidates as Leaving Groups: Structure/Reactivity Correlation of the Hydroxide-Dependent E1cB-like Breakdown of Carbinolamides in Aqueous Solution

Kinetic dependence of the aqueous reaction of N-(hydroxymethyl)benzamide derivatives upon addition of electron-withdrawing groups.

Nucleofugality of the benzotriazole group in solvolysis

Determination of the pKa of cyclobutanone: Brønsted correlation of the general base-catalyzed enolization in aqueous solution and the effect of ring strain.