Samuel Lamdan

1,2-Diaryl-2-imidazolines. A structure–basicity relationship: application of the Hammett equation

The pKa values of sixteen 1,2-diaryl-2-imidazolines have been determined and the influence of substituents at N-1 and C-2 upon basicity have been studied. The experimental data have been successfully correlated with the Hammett equation, the imidazoline ring being considered a substituent of the benzene ring. Comparisons with aniline and amidine systems have also been made.

Synthesis and properties of 1,2-diaryl-4,5,6,7-tetrahydro-1H-1,3-diazepines and 1,2-diaryl-1,4,5,6,7,8-hexahydro-1,3-diazocines. Comparison with the five- and six-membered homologues

The cyclization of N-aroyl-N′-aryl-tetra- and -penta-methylenediamines with ethyl polyphosphate afforded 1,2-diaryl derivatives of 4,5,6,7-tetrahydro-1H-1,3-diazepines and 1,4,5,6,7,8-hexahydro-1,3-diazocines respectively. To compare the basicity of these compounds with that of the five- and six-membered homologues, their pKa values were determined. The pKa values decrease in the order: tetrahydropyrimidines > tetrahydrodiazepines > hexahydrodiazocines > imidazolines. Rate constants for the hydrolysis of a series of homologues were determined in boiling alkaline 95% ethanol. It was observed that stability to alkaline hydrolysis increases in the order: imidazolines < tetrahydropyrimidines tetrahydrodiazepines < hexahydrodiazocines. With these and other data, some conformational aspects were analysed.

Semiempirical CNDO/2 calculation of the electronic structure of the DNA molecule I. Ground state potential curves; Tunneling and tautomeric equilibrium in the NHN and OHN bonds of the adenine-thymine base pair

Abstract The ground electronic state structure of the double hydrogen bond in the adenine-thymine nucleotide base pair has been investigated in the semi-empirical CNDO/2 approximation. Potential curves are obtained for several nuclear configurations characterizing both, single and simultaneous tautomeric rearrangements of the NHN and NHO bonds. The results indicate two relative minima corresponding to the normal and tautomeric forms for the coupled motion of the two protons. For the single displacement, the bond energy analysis shows that W A-T (R, r) is repulsive in such a way that W A−T (R, r) + W A−H (R, r) -I- W T−H (R, r) shows only one minimum. These results are in agreement with earlier studies on the hydrogen bond in the guanine-cytosine base pair utilizing ab initio techniques. The atom-atom bond index curves for several pairs of atoms are given and some molecular orbitals have been correlated in the normal and tautomeric forms. Estimates are made within the WKB approximation of the tunneling rate and tunneling probability. The magnitude of the equilibrium distribution between the normal and tautomeric proton positions of minimum energy is consistent with the idea that simultaneous double proton tunneling in the ground state is not significant, thus ruling out a possibility for an error mechanism in the genetic code.

Alkaline hydrolysis of 1,2,3-trisubstituted cyclic amidinium salts. Kinetic study of N → N′ acyl migration in alkaline solution in an ethylenediamine derivative

The alkaline hydrolysis of 1,2-diphenyl-3-methylimidazolinium iodide (1) affords N-benzoyl-N-phenyl-N′-methylethylenediamine (2). An intermediate of the reaction, probably 1,2-diphenyl-2-hydroxy-3-methylimidazolidine (8), was isolated by thick layer chromatography. Compound (2) in neutral or alkaline media undergoes intramolecular aminolysis affording N-benzoyl-N-methyl-N′-phenylethylenediamine (3) by benzoyl transfer. Kinetic studies were performed on this reaction over the pH range 11.65–12.80. Compound (2) appears to rearrange by a mechanism which involves the formation and catalysed decomposition of a tetrahedral addition intermediate. This intermediate is the same as that isolated by alkaline hydrolysis of (1). Pseudo-first-order rate constants show a first-order dependence on hydroxide ion activity all over the pH range studied indicating that the contribution of the anionic species of the intermediate is negligible under the experimental conditions. The alkaline hydrolysis of the 1,2-diphenyl-1,4,5,6-tetrahydropyrimidinium iodide (9) allowed the isolation of only the rearranged product N-benzoyl-N-methyl-N′-phenyltrimethylenediamine (10).

Molecular orbital theory of the electronic structure of organic compounds—II: Transannular interactions in dioxodiazacycloalkanes

Abstract The CNDO/2 MO and INDO MO methods were used to study the molecular electronic structure of the bicyclic molecules derived by transannular interaction of the amide groups in two isomeric dioxodiazacyclo-decanes. A physical model based on the invariance of the MOs with respect to linear transformation of the basis set allowed to determine a functional relation between the bond atomic population M C-N and r C-N (transannular) in a set of closely related lactams (dioxodiazacycloalkanes). Further, the stabilities of a set of cyclopeptides as determined by Shemyakin et al. allowed to calculate a minimum value of M C-N and a maximum transannular distance r C-N beyond which is not possible the transannular interaction between the amide groups in this kind of molecules. These approaches were used together to provide quantitative results which enable to account for the different behaviour of 6,10-dioxo-l,5-diazacyclodecane and 4,10-dioxo-1,5-diazacyclodecane towards ring contraction reactions.

Reaction of an asymmetric imidazolinium compound with nucleophiles

1-Methyl-3-(p-nitrophenyl)-2-phenylimidazolinium iodide (2) reacts easily with nucleophiles to give addition products of various stabilities. In sodium hydroxide or a silver oxide suspension compound (2) reacted to give N-benzoyl-N-methyl-N′-(p-nitrophenyl)ethylenediamine (4), the structure of which was confirmed by synthesis from N-(2-bromoethyl)-N-methylbenzamide and p-nitroaniline. Treatment of compound (2) with IRA-400 resin (OH–) afforded the imidazolinium hydroxide which rearranged to (4). Reaction of (2) with sodium methoxide in anhydrous methanol afforded 2-methoxy-1-methyl-3-(p-nitrophenyl)-2-phenylimidazolidine which was hydrolysed readily to (4). Sodium borohydride reduces (2) to 1-methyl-3-(p-nitrophenyl)-2-phenylimidazolidine.

Molecular Orbital Theory of the Electronic Structure of Organic Compounds I. Dioxodiazacycloalkanes

Abstract The stability of some heterocyclic compounds derived from the condensation of succinic and glutaric anhydrides with aliphatic diamines is compared using calculated values for the total energies. Further, some results derived from the electronic population analysis and the available experimental data are used to give information about the corresponding electronic structure. The CNDO/2 and INDO methods have been used for the calculations.

Basicity and alkaline hydrolysis of 1,2-diaryl-1,4,5,6-tetrahydropyrimidines. Application of the Hammett equation

The pKa values of nine 1,2-diaryl-1,4,5,6-tetrahydropyrimidines have been determined spectrophotometrically. The influence of substituents at N-1 and C-2 upon basicity has been studied. When the tetrahydropyrimidine ring is considered to be a substituent of the benzene ring at N-1, a good correlation with the Hammett equation is found. The stability of these compounds to hydrolysis in boiling alkaline 95% ethanol was studied. Reaction rates were enhanced by electron-releasing phenyl substituents at N-1 and reduced by electron-withdrawing groups. Agreement with the Hammett equation allowed calculation of rate constants. The observed and calculated rate constants of hydrolysis are nearly equal. An equation relating the rate constants with the ionization constants of tetrahydropyrimidinium ions is given.