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 polarographic half-wave potentials of a number of 8-nitrostyrenes, p-nitropropenylbenzenes, and p-nitrobutenylbenze~les havc been determined in aqueous ethanolic solution a t an apparent pH of 6.54. A linear relationship exists between these values and Ilammett sigma constants, but not with their ultraviolet absorption maxima or with their dipole moments.The polarographic wave of 11 diethyl benzaln~alonates, under the same conditions, was masked by the hydrogen wave.Nitro groups are reducible a t the dropping-mercury cathode, and their half-\\rave depend upon the solvent%nd upon ~vhether it is a n isolated or an aro~natic llitro group. Holleck and Ja~lllalcoudalcis (2) state that the nitro group of ,&nitrostyrene sho\vs some properties characteristic of the above tn-o classes.In an acid rnediunl nitroalkanes exhibit 011ly one polarographic wave, which varies little with PI-I (-0.75 to -0.89 V over a range of 3 pIH units) ; a t PI-I 4.3 a second \\rave starts a t -1.5 V which is obscured by the hydrogen wave (1). In an alkaline medium the diffusion current of the nitroallcanes falls with time because of equilibration with the non-reducible aci-form (1). Reduction of the nitro group a t the dropping-mercury electrode is an irreversible, four-electron process which leads to the respective hydroxylamine. The second wave, a t more negative potentials, involves the reduction of the alkylhydroxylammonium ion to the al1;ylamnlonium ion and is a t\vo-electron process (I).Aromatic nitro compounds, except for the o-and p-nitroanilines, the o-and p-nitrophenols, and the o-and 9-dinitrobenzenes, behave siinilarly, except that the half-wave changes linearly with pH over a t least part of the pH scale. At pH < 5 nitrobenzene gives two waves involving four electrons and two electrons to give the respective -phenylhydroxyla~~~ine and The exceptions noted above are abnormal, because the resulting phenylhydroxylamine can lose water t o give a reducible quinonoid structure (1, 3). Illtroduction of one or two methyl groups into the benzene ring has little effect upon the half-wave potential of the nitrobenzene unless the two methyl groups are both ortho to the nitro group (see Table 11); when the half-\\rave potential is shifted to lllore negative values (I). Such effects are noted when the functional group, such as nitro, can -undergo a marlied meso~llerisn~ with the aromatic ring, and \\rhen both the functional group and the ortho substitrlents are bulky (1,4). The nitro group then should, and does, behave more like an aliphatic nitro group toward polarographic reduction (I). I t has been stated (4) that differences in the half-wave potentials of ortho-and para-substituted ~nembers of this series give an insight into the nature and extent of certain types of ortho 'Issued as Szifield Teclmical Paper No. 319,

Partition coefficients in cyclohexane-water were determined for 160 conjugated heteroenoid compounds and were used to calculate n constants for several component groupings of molecules.