The reactions of 2-benzal-1,3-indanediones and the cyano-containing benzalmalononitriles, ethyl benzalcyanoacetates. be~lzalcyanoacetamides, and benzalcyanoacetanilldes with 12-butanethiol at 25 "C in 20%kthanol-80% pH 7 buffer attain equlibrium at a rate too fast to measure by standard methods.The equilibrium constants have been calculated and these in turn related to Hammett o and Taft o* constants. The differences in the reactions of these and other gem difunctional systems which react virtually completely with 12-butanethiol under the same experimental conditions and at a measurable rate, are attributed to participation of the functional group cis to the phenyl group in the reverse reaction. It is shown that 12-butanethiol adds to cinnamalacetophenone by a 1,4-mechanism and the reactions of this nucleophile with similar compounds having extended conjugated systems are discussed.

A series of 107 1,4-naphthoquinones and related products has been synthesized to study their mode of action in bacterial growth inhibition. The itz vitro reactions of a number of these with aniline, 11-butylamine, sodium methoxide, and an 11-buthanethiol -triethylamine mixture have been examined. A series of epoxides of C-2 monosubstituted and C-2,C-3 disubstituted 1,4-naphthoquinones has been synthesized and their reactions with amines, thiols, and halogen acids have been studied. The ultraviolet absorption maxima of many of these quinoncs are also tabulated.Canadian Journal of Chemistry, 46, 1859 (19GS) A number of 1,4-naphthoquinones were synthesized to determine their growth inhibitory activities against Stuphylococcus aureus (1) and also the relation of these activities to their partition coefficients in cyclohexane-water (2) and to their polarographic half-wave potentials (3). The inhibitory activities were independent of partition coefficients1 but exhibited a direct relationship to their polarographic half-wave potentials. The logarithms of the growth inhibitory activities for 1,4-naphthoquinones with unreactive groups at C-2 and C-3, when plotted against their half-wave potentials, gave two maxima, oile at -0.23 V and a less pronounced maximum at -0.36 V. The 1,4-naphthoquinones with a free position or a reactive group at C-2 or C-3 gave similar results when the logarithms of the growth inhibitory activities were plotted against the polarographic half-wave potentials of their C-2 or C-3 n-butylthio analogues. This was not true when their C-2 or C-3 amine analogues were used.These results (1) support the postulate (6) that 1,4-naphthoquinones or compounds such as 1,4,4a,9a-tetrahydroanthraquinone (7) which are readily converted to 1,4-naphthoquinones, function as bacterial growth inhibitors by functioning competitively in electron transport with the endogenous vitamin K or ubiquinone, thus decreasing the effectiveness of the latter as oxidative phosphorylating agents. For 1,4-naphthoquinones with unreactive groups at C-2 or C-3 to be effective growth inhibitors, this requires that their half-wave potentials lie between -0.163 to -0.307 V or -0.314 to -0.536 V (6) and that maximum effectiveiless should be intermediate between these limits. The 1,4-naphthoquinones with a free position or a reactive group at C-2 or C-3 may react with a bacterial protein-thiol or protein-amine prior to f~lnc-tioning as growth inhibitors, in which case the half-wave potentials of the derived 1,4-naphthoquinones must lie between these limits with maximum effectiveness intermediate between these limits. This paper reports the synthesis of a number of 1,4-naphthoquinones along with model 11-butylthio-, phenylthio-, n-butylamino-, and anilinoderivatives. The reactions leading to the model protein analogues were also used to classify substituents at C-2 and/or C-3, at least, in vitro, as reactive or unreactive and to demonstrate where these reactions did not follow the normal course.Anilino derivatives of the 1,4-naphthoquinone...

A series of 326 3-benzal-2,4-pentanediones, 2-benzal-1,3-indanediones, ethyl benzalaceto-acetates, diethyl benzalmalonates, ethyl benzalcyanoacetates, benzalmalononitriles, benzalcyanoacetamides, benzalcyanoacetanilides, benzalmalonamides, β-nitrostyrenes, β-nitropropenylbenzenes, β-nitrobutenylbenzenes, and derivatives of a number of cinnamic acids have been synthesized and their geometric configuration discussed. Aniline, p-toluidine, and n-butanethiol have been added to some of these compounds. The aniline adducts have also been prepared from benzylideneaniline and the active methylene compounds. The aniline adducts of those containing a cyano group are not stable and lose aniline at room temperature. The structure of the compound prepared from benzylideneaniline and ethyl cyanoacetate and melting at 140 °C has been established.

The concept of additive constants to predict the partition coefficient of a compound has been developed and applied to 244 compounds. Some of the limitations of such a concept are discussed.

The nuclear magnetic resonance spectra of a series of substituted benzaln~alo~lonitriles were examined in various solvents. The chemical shifts for the olefinic protons are susceptible t o large solvent effects which are interpreted as arising from association of a solvent molecule with the olefinic proton (acetone) or a site in its vicinity (benzene). With acetone this leads to a downfield shift from values observed in chloroform.