CuAAC and RuAAC with Alkyne-functionalised Dihydroazulene Photoswitches and Determination of Hammett σ-Constants for Triazoles

Dihydroazulene (DHA)–vinylheptafulvene (VHF) photoswitches have attracted attention as potentially useful components in molecular electronics. The π-conjugated dihydroazulene system is a rigid structure and can be strategically functionalised to place handles for further elaboration. Here we show that alkyne-functionalised dihydroazulenes can be subjected to copper and ruthenium catalysed azide–alkyne cycloadditions (CuAAC and RuAAC) with tolylazide, furnishing 1,4- and 1,5-disubstituted triazoles. The rates of ring-closure of the corresponding vinylheptafulvenes were compared with those of reference systems, which allowed determination of Hammett substituent constants (meta and para) for N-tolyl-substituted 1,2,3-triazoles.

Reaction of N-Acyloxy-N-alkoxyamides with Biological Thiol Groups

Mutagenic N-acyloxy-N-alkoxyamides 1 react with thiols by an SN2 process at nitrogen with displacement of carboxylate. They react with glutathione 4 in [D6]DMSO/D2O and methyl and ethyl esters of cysteine hydrochloride, 11 and 12, in [D4]methanol but the intermediate N-alkoxy-N-(alkylthio)amides undergo a rapid substitution reaction at sulfur by a second thiol molecule to give hydroxamic esters and disulfides. Arrhenius activation energies and entropies of activation obtained for a series of different N-benzyloxy-N-(4-substitutedbenzoyloxy)benzamides 13–17 were similar to those found for the SN2 reaction of the same series with N-methylaniline. Entropies of activation were strongly negative in keeping with polar separation and attendant solvation in the transition state, and in keeping with this, bimolecular reaction rate constants at 298 K correlated with Hammett σ constants with a positive ρ-value of 1.1. The structure of model N-methoxy-N-(methylthio)acetamide has been computed at the B3LYP/6–31G(d) level and exhibits properties atypical of other anomeric amides with more electronegative atoms at nitrogen. Relative to N,N-bisoxyl substitution, the combination of a sulfur and an oxygen atom at the amide nitrogen results in a relatively small reduction in amide resonance.

Lower Bounds to Hammett σ Constants for meta and para Normal Substituents

Twenty-four pairs of meta and para Hammett σ constants recommended by IUPAC for normal substituents, i.e. dipolar groups without a lone pair of electrons (and with a full octet) in the atom next to the aromatic ring, were analysed with respect to their meta-para interrelationship. In terms of a previous hyperbolic model, the para/meta ratio of the universal electric effect is found to be 0.964 with a standard error of 0.028 estimated by Monte Carlo simulation. This value for benzoic acid derivatives supports the view that the universal electric effect, which is proposed to be termed the Electra effect, is transmitted through space. For normal substituents, it is demonstrated that the hyperbolic model predicts lower bounding values of σm and σp constants. It is proposed that organometallic substituents in which a metallic atom is bounded to the α carbon should not be considered as normal substituents. It is asserted that no normal substituent should exist for which either σm is less than -0.1 or σp is less than -0.3 in the Hammett σ scale.

Polarographic Determination of 4'-Substituted Derivatives of 3-Carboxy-4-hydroxy-6-acetylaminoazobenzene

Tast polarography, differential pulse polarography and cyclic voltammetry were applied to the examination of 7 derivatives of 3-carboxy-4-hydroxy-6-acetylaminoazobenzene with H, CH3, OCH3, Cl, COCH3, NO2 and NHCOCH3 substituents in position 4'. A general reduction mechanism was suggested for the substances. The half-wave potentials obtained from tast polarographic measurements were correlated with the Hammett σ constants of the substituents in the para-position. The plot of this dependence is linear, which suggests that the reduction mechanism is identical within the entire series. The optimum conditions for quantitation of the substances were found within the concentration regions of 1 .10-4 to 1 .10-6 mol l-1 for tast polarography and 1 .10-4 to 1 .10-7 mol l-1 for differential pulse polarography.

Kinetics of the reduction of nicotinonitrile cations by 1,4-dihydronicotinamides

The rates of reduction of a series of 1-(Z-benzyl)nicotinonitrile cations by a series of 1-(X-benzyl)-1,4-dihydronicotinamides have been studied at 25 °C in 20% CH3CN – 80% H2O (pH 7.0 (5 mM phosphate), ionic strength 1.0 (KCl)). Spectral studies indicate the formation of 1,4-dihydronicotinonitrile products, without the formation of the isomeric 1,2-dihydro- or 1,6-dihydro-nicotinamide intermediates. Second-order rate constants (k2) for these reductions are closely correlated with the Hammett σ constants for X and Z. Thus, for X = H, log k2 = 0.63σz − 1.05, while for Z = 4-CN, log k2 = −0.64σx − 0.65. The close correspondence between these ρx and ρz values indicates that charge neutralization on the nicotinonitrile cation exactly balances charge generation on the nicotinamide cation product in the rate-determining transition state. Thus the migrating hydrogen species is electrically neutral in the rate-determining transition state, which contrasts with the hydridic transition states previously reported in the reduction of isoquinolinium cations by 1,4-dihydronicotinamides. When 1-benzyl-4,4-dideuterio-1,4-dihydronicotinamide is used as the reductant, primary kinetic isotope effects of 3.0 and 2.7 are observed for the reduction of the 1-methylnicotinonitrile and 1-(4-cyanobenzyl)-nicotinonitrile cations, respectively. These data are evaluated in terms of the various mechanistic possibilities for hydride transfer.

Linear Free Energy Relationship Involving the Properties of Prevulcanization Inhibitors

The utilization of σ* constants for substituted phenyl groups converted from the known Hammett σ constants of the phenyl substituents is useful in assessing the linear free energy relationship (LFER) of the properties of various inhibitors. The inhibitors include thioketals, sulfenamides and N,N′thiobis(substituted formanilides). In the LFER of the rate of reaction between thioketals with 2-mercaptobenzothiazole, the rate is fastest when the thio group of the thioketal is attached to a substituted phenyl with the highest positive σ constant. The σ constant of alkyl groups is negative, and an alkylthio group gives a thioketal with a slower reaction rate. The LFER applies to the 13C NMR shift of the quaternary carbon of the thioketals with alkylthio groups. The slope of the linear relation is positive. However, changes in the 13C NMR shift of the arylthio derivatives are relatively small in spite of a wide variation in σ* constant. The LFER applies to the scorch delaying activities of all structural types of inhibitors in stocks accelerated by various benzothiazoles. In the linear relationship of scorch delay versus σ* constant in each type of inhibitor, the slope is negative. Variables with negative σ* constants give longer delay and those with more positive σ* constants give shorter delay. An exception is in the very fast curing MSSM/DPG stock where the thioketals from acetoacetanilide with arylthio groups give longer delay than the alkylthio compounds. In the TBBS-accelerated stock, the slopes of the linear relation of the carbamate sulfenamides, N,N′-thiobisformanilides and thioketals of cyanoacetanilides are about equal. However, the level of scorch delay obtained with the sulfenamides is significantly higher than the other two, which are equal in inhibition level. The inhibition action of N,N′-thiobisformanilides without alkylthio or arylthio groups is probably due to the formation of labile formanilide polysulfide intermediates.

Oxidation of (1-hydroxybenzyl)ferrocene and its derivatives substituted in phenyl ring with bis(triphenylsilyl) chromate

Kinetics have been studied of oxidation of (1-hydroxybenzyl)ferrocenes substituted in phenyl ring with bis(triphenylsilyl) chromate in benzene solutions as well as protonation of these alcohols in sulphuric acid medium. Logarithms of the oxidation rate constants (kobs, 20-40 °C) and those of the protonation equilibrium constants (KR+, 25 °C) show linear dependence on the Hammett σ constants, the ρ constant values being -0.86 to -0.40 and -2.50, respectively. These negative values suggest that the both processes are influenced by the same effects and confirm the mechanism proposed earlier for oxidation of alcohols with ferrocenyl substituent by action of bis(triphenylsilyl) chromate in aprotic solvents.