Gouki Fukata

The mechanism of imine–enamine tautomerism of 2- and 4-phenacylquinolines

Isomerisations of 2- and 4-phenacylquinolines to their enaminone tautomers via 1,3 or 1,5 carbon–nitrogen hydrogen shifts occur by stepwise acid- or base-catalysed pathways similar to those for the enolisation of ketones. The reactions are observed as relaxations of the unstable to stable tautomers by stopped-flow spectrophotometry or, where the aromatic imine is the stable form, by trapping the enaminone with iodine in the reverse reaction. Evidence of mechanism comes from observations of general acid and general base catalysis, agreement between kinetically determined pKa values and independently measured values, and comparisons between rate and equilibrium constants for protonation of the enaminone tautomers and their N-methyl derivatives. The reactions show a primary isotope effect and yield normal Bronsted plots with αca. 0.5. The kinetically determined pKa values indicate N- rather than O-protonation of phenacylquinolines but for the enaminones O-protonation competes kinetically with the thermodynamically preferred C-protonation. Combination of pKa values for C-, N-, and O-protonation leads to equilibrium constants KT for enamine–imine and (protonated) keto–enol tautomerisation. The effect of 2- and 4-N-protonation (proton activating factors) upon rates and equilibria for ionisation of hydrogen from the methylene carbons is discussed and evidence of ‘imbalance’ in charge development on the carbon base in the transition state is noted. A concerted intramolecular 1,3-proton transfer is predicted but not observed.

Enamine–imine tautomerism of benzyl- and phenacyl-quinolines

Measurements of tautomeric constants KT for enamine–imine equilibria of 2-benzyl-, 2-phenacyl-, and 4-phenacyl quinolines give values of log KT of 8.7, –1.1, and 1.8 respectively, which may be compared with values for the corresponding 2- and 4-pyridines. For the stable enamine of 2-phenacylquinoline a test of the assumptions on which evaluations of KT are usually based, that N-methyl and N-H enamines have the same pKa values and extinction coefficients, shows differences of two units in pKa values and 30% in extinction coefficients. For the N-methyl enamine, however, the n.m.r. spectrum points to a trans-arrangement of nitrogen and carbonyl group rather than the hydrogen-bonded cis conformation likely for the N-H compound. Interference with nitrogen-carbonyl conjugation through interaction of the N-methyl group with a hydrogen at the 8-position of the remote quinolyl ring is suggested as destabilising the cis-conformation in the N-methyl case.

Preparation of all the possible ring-deuteriated benzoic acids by reductive dehalogenation of the corresponding halogenobenzoic acids with raney alloys in an alkaline deuterium oxide solution

All the possible undeuteriated benzoic acids were prepared mainly by treatment of the corresponding bromobenzoic acid with Raney Cu–Al alloy in 10% NaOD–D2O solution. [2,3,4,5,6-2H5] Benzoic acid was obtained from pentafluorobenzoic acid by a similar reaction. However, only [2,3,4,5-2H4] benzoic acid was prepared by decarboxylation of [2,3,4,5-2H4] phthalic acid.

Regioselectivity of Friedel-Crafts Acylation of Aromatic Compounds With Several Cyclic Anhydrides

The Friedel-Crafts acylations of various aromatic compounds with cyclic anhydrides such as 2-(p-substituted phenyl)butanedioic, 3-phenylpentanedioic and homophathlic anhydrides were carried out under various conditions in order to obtain informations about the regioselectivity of the ring opening of the cyclic anhydrides and about the possible reaction pathways in the acylations.

Reduction of 1-(2-hydroxy-3,5-di-t-butylphenyl)pyridinium halides and their zwitterions. Formation of di- and tetra-hydropyrido[2,1-b]benzoxazoles

Reduction of 1-(2-hydroxy-3,5-di-t-butylphenyl)pyridinium halides (1a–d) and/or their zwitterions (2a–d) with Raney Ni–Al alloy, Raney Ni (W2) and NaBH4 were investigated. When (1) was treated with Ni-Al alloy in a mixture of methanol and 30% aqueous KOH, novel cyclization products, 1,2,3,4-tetrahydro-(5a–d) and 3,4-dihydro-pyrido[2,1-b]benzoxazoles (6a) and (6b) were obtained. Raney Ni catalyzed hydrogenation of (1a), (1b), (2a), (2b), and (2d) gave (5) and/or 2-piperidinophenols (4). Reduction of (1b) and (1d) with NaBH4 was re-examined and 1,2-dihydro-(7) and 1,4-dihydro-pyrido[2,1 -b]benzoxazole (8) were isolated, respectively, as byproducts.

Ring-opening Reaction of 6,8-Di-t-butyl-1,2,3,4-tetrahydro-9aH-pyrido [2,1-b] benzoxazole

Treatment of 6, 8-di-t-butyl-1, 2, 3, 4-tetrahydro-9aH-pyrido [2, 1-b]benzoxazole (3a) with conc, hydrochloric acid gave 2,4-di-t-butyl-6-piperidino-phenol (4) and 2,4-di-t-butyl-6-(2-oxopiperidino)phenol (5) in 26 and 25% yields. Reaction of 3a with acetic anhydride afforded 2,4-di-t-butyl-6-[1-(1, 2, 3, 4-tetrahydro-5-acetylpyridyl)] phenyl acetate (6) and 6, 8-di-t-butyl-1-acetyl-2, 3, 4, 4a-tetrahydropyrido [2, 1-b] benzoxazole (7) in 41 and 25% yields. Hofmann degradation of the quarternary salts of 3a with methyl and ethyl iodide gave the expected ring-opend [1, 4] oxazonines, 10a and 10b, in 43 and 10% yields, respectively.

Cyclodienones. Part 8. Hydrolysis of 5-oxo-2,4-di-t-butylcyclopenta-1,3-dienecarbonitrile

The acid-catalysed hydrolysis of 5-oxo-2,4-di-t-butylcyclopenta-1,3-dienecarbonitrile (2) gave the novel products 3,3a,6,6a-tetrahydro-3,3,3a-trimethyl-5-t-butyl-1H-cyclopenta[c]furan-1,6-dione (5), 4,5-dimethyl-7-t-butylbicyclo[3.3.0]octa-3,6-diene-2,8-dione (6), and 2-carbamoyl-5-isopropylidene-3-methylcyclopent-2-enone (7), but not the expected carboxylic acid (3). Treatment of compound (5) with 10% NaOH followed by acidification with 10% HCl gave, in 88% yield, the unexpected 2-methyl-5-oxo-4-t-butylcyclopent-1-enecarboxylic acid (8) which, on thermolysis, gave 3-methyl-5-t-butylcyclopent-2-enone (9) and 4-methyl-2-t-butylcyclopent-3-enone (10) in 51 and 36% yields, respectively.The base catalysed hydrolysis of compound (2) has also been attempted.

Cyclodienones. Part 6. Preparation of 4-azido-2,4,6-tri-t-butyl-cyclohexa-2,5-dienone and its thermal, photo-, and acid-catalyzed decomposition

Preparation of 4-azido-2,4,6-tri-t-butylcyclohexa-2,5-dienone (3) from 4-bromo-2,4,6-tri-t-butylcyclohexa-2,5-dienone (1) and sodium azide is described. Treatment of (3) with concentrated sulphuric acid afforded 2,6-di-t-butyl-p-benzoquinone (7) in 75% yield, while the reaction at –10 °C in chloroform solution gave a tri-t-butylazepinone (5) and 3,5-di-t-butyl-o-benzoquinone (8). Photolysis of (3) in benzene afforded 2,4-di-t-butylcyclopenta-2,4-dienone (11), which was isolated as the dimer (12). Thermolysis of (3) in boiling toluene gave 6-amino-2,4-di-t-butylphenol (17), 2,4,6,8-tetra-t-butyl-1H-phenoxazin-1-one (21), and 2-cyano-9,9a-dihydro-3,5,7,9a-tetra-t-butylcyclopenta[b][1,4]benzoxazin-1(3aH)-one (22) in 15,15 and 48% yields, respectively. When the thermolysis was carried out with very low reagent concentrations, 5-cyano-2,4-di-t-butylcyclopenta-2,4-dienone (23), in addition to the phenol (17), was obtained. The compound (23) was also obtained by thermolysis of (3) in boiling acetic anhydride and in boiling toluene containing acetic anhydride. The reaction pathway for the formation of compounds (17), (22), and (23) on thermolysis of the azide (3) is also discussed.