W. Brian Jennings

E–Z-isomerism in aldimines

A range of ortho-disubstituted C-aryl aldimines has been synthesized. N.m.r. spectroscopic analysis revealed a significant proportion of the Z-isomer at equilibrium in solution. The E–Z-isomer distribution is critically examined in terms of electronic, steric, and solvent effects. The effect of trace amounts of carboxylic acid on imine stereomutation is discussed.

Evaluation of the Bruker SMART X2S: crystallography for the nonspecialist?

An evaluation of the Bruker SMART X2S for the collection of crystallographic diffraction data, structure solution and refinement is carried out with a variety of materials with different electron densities, presenting some of the successes and challenges of automation in chemical crystallography.

Ring transformation of furfural into an unusual bicyclic system: Characterisation and dynamic stereochemistry of 6,7-diethoxycarbonyl-6,7-diaza-8-oxabicyclo[3,2,1]oct-3-en-2-one

Abstract 2-Formylthiophene and 3-formylindole react with diethyl azodicarboxylate to give simple products derived from reactions on the formyl group whereas 2-formylfuran reacts to give the unexpected bicyclic title compound. 1 H and 13 C NMR studies indicate that this compound undergoes a series of three dynamic conformational changes over the temperature range 50 to −90°C which are ascribed to slow rotation about the exocyclic carbamate bonds and hindered bridge inversion.

Equilibrium distribution of E–Z-ketimine isomers

The ratio of E–Z-imine isomers at equilibrium is dependent on resonance stabilization, non-bonding interactions, substitution, and solvent. Stereochemical assignments are based upon i.r. and n.m.r. data.

Topically resolved intramolecular CH-π interactions in phenylalanine derivatives

NMR spectra of imines and nitrones derived from benzophenone and phenylalanine or tyrosine show clear evidence of an aromatic edge-to-face interaction in solution. At low temperatures the two ortho protons of the edge interacting phenyl ring become topically resolved with the ortho proton NMR signal involved in the CH-pi interactions shifted well upfield (delta 5.4-5.8 at -88 degrees C) of the other ortho signal. Introduction of a para substituent into the phenylalanine ring has a modest effect on the upfield shift. The edge-to-face arrangement also manifests in the X-ray crystal structures of two of these compounds. Barriers to rotation around the syn phenyl-imino bond are also reported (10.5-11.1 kcal mol(-1)).

Dynamic stereochemistry of imines and derivatives. Part 11. Synthesis and stereochemistry of (E)- and (Z)-nitrones

A range of hindered nitrones [ArCR:N(O)R′; R = H or alkyl] has been synthesized and their stereochemistry has been assigned. The relative proportions of (E)- and (Z)-nitrone isomers at equilibrium were found to be both substituent- and solvent-dependent. The mechanism of the oxidation of imines to nitrones by peroxy-acid is discussed in relation to the reactant and product stereochemistry. The acidic hydrolysis of N-(pentamethylphenyl-methylene)alkylamine N-oxides has been used as a general synthesis of N-alkylhydroxylamines.

Dynamic stereochemistry of imines and derivatives. Part IX. The mechanism of E–Z isomerization in N-alkylimines

Rates of E–Z isomerization in N-alkylimines have been determined by direct thermal stereomutation and by dynamic n.m.r. spectroscopy. Thermal racemization rates of optically active para-disubstituted 2-t-butyl-3.3-diphenyloxaziridines have also been measured, and show a small but consistent correlation with Hammett σp. Comparison of the activation parameters for imine isomerization with data for nitrogen inversion in oxaziridines indicates that N-alkylimines isomerize by a planar inversion (lateral shift) mechanism. Barriers determined for an aldimine under optimal conditions are higher than previously reported for imines (ca. 30 kcal mol–1).

On the chirality of 2-hydroxy-NN-dialkythiobenzamides. Demonstration of three consecutive conformational processes

The geminal anisochronism observed in the 1H n.m.r. spectra of some of the title compounds has previously been ascribed to different causes. It has now been unequivocally shown that the geminal anisochronism is a consequence of the molecular chirality arising from slow rotation of the aryl ring with respect to the thioamide group. The free-energy barrier to this process has been found to lie in the range 11.2–13.4 kcal mol–1, increasing with the size of the N-alkyl groups. A lower energy process (ΔG‡= 8.6 kcal mol–1) in 2-hydroxy-NN-di-isobutylthiobenzamide has been identified as the exchage of the isobutyl groups between two anti-periplanar positions. The third process with the highest barrier in each case (ΔG‡= 13.4–15.6 kcal mol–1) is the E–Z exchange of the alkyl groups by rotation around the C(S)–N bond.

Dynamic stereochemistry of imines and derivatives. Part VI. Stereochemistry of the peroxyacid–imine route to oxaziridines

The stereochemistry of the peroxyacid oxidation of N-alkyl-aldimines and -ketimines to oxaziridines containing a stable nitrogen pyramid is considered over a range of reaction conditions. The possible relevance of reactant and product molecular geometry in distinguishing between the concerted and stepwise mechanisms is discussed. A comparison is made between rate constants of several peroxyacid oxidation reactions in different solvents. The concerted mechanism appears to be less attractive on the basis of stereochemical and solvent effect data.

Dynamic stereochemistry of imines and derivatives. Part VIII. Barriers to rotation around the carbon–nitrogen bond in imine N-oxides (nitrones)

Semiempirical molecular orbital calculations (CNDO/2 and INDO) are reported for methyleneamine N-oxide, N-(benzylidene)methylamine N-oxide, and diphenylmethyleneamine N-oxide. The calculated dipole moments and the energy difference between E- and Z-isomers are in good agreement with experimental data in solution. The calculated barriers to rotation around the CN bond are about twice the measured barriers to E–Z-interconversion in closely related nitrones. Experimental data for E–Z-isomerization in N-(9-anthrylmethylene)methylamine N-oxide shows the entropy of activation to be close to zero as expected for a rotational process.