Lilian C. Monahan

3-Hydroxypyrroles and 1H-pyrrol-3(2H)-ones. Part 2. Scope and limitations of the synthesis of pyrrol-3-ones by pyrolysis of aminomethylene Meldrum's acid derivatives

Flash vacuum pyrolysis of N,N-disubstituted aminomethylene Meldrums acid derivatives provides a route to 4,5-unsubstituted 1H-pyrrol-3(2H)-ones by a hydrogen-transfer–cyclisation sequence. Alkyl and aryl 1-substituted, 1,2-disubstituted, and 1,2,2-trisubstituted pyrrolones can be obtained. In competitive cases, there is little selectivity between hydrogen transfer from primary, secondary, or tertiary sites, although benzyl hydrogen atoms proved particularly reactive, giving a general synthesis of 2-phenyl-1H-pyrrol-3(2H)-ones.

3-Hydroxypyrroles and 1H-pyrrol-3(2H)-ones. Part 8. Reactions of 1-isopropyl-2,2-dimethyl-1H-pyrrol-3(2H)-one with electrophiles

Reaction of the pyrrolone (2) with N-, C-, and halogen-electrophiles takes place at the 4-position to give the azo compounds (3)–(5), the ‘methylene Meldrum’s′ derivative (12) and the halogeno derivatives (16)–(18). Reductive cleavage of the azo compound (5) gives a convenient route to the 4-aminopyrrolone (7), which may be diazotised and coupled with 2-naphthol. Decomposition of the Meldrums derivative (12) with base leads to the malonates (13) and (14) and acrylate (15). Deuterium exchange at the 5-position takes place when the halogeno compounds (16)–(18) are treated with [2H3]methoxide in [2H4]methanol: the 5-anion is thought to be an intermediate. Protodehalogenation of the 4-bromo- and 4-iodo-derivatives (17) and (18) occurs on treatment with triphenylphosphine.

Variable-temperature NMR and X-ray crystallographic studies of 5-dimethylaminomethylene-, 5-dimethylaminopropenylidene-, and 5-(5-dimethylaminopenta-2,4-dienylidene)-derivatives of Meldrum's acid and related dimethyl malonate derivatives

Variable-temperature 1H and 13C NMR studies of the title Meldrums acid derivatives and the corresponding malonates show in most cases coalescence phenomena due to C–N and CC rotation effects. The trends in free energies of activation for these processes are examined with respect to the X-ray crystal structures of the Meldrums acid derivatives which show effects of electron delocalisation in the conjugated system.

3-Hydroxypyrroles [pyrrol-3(2H)-ones]

Simple 3-hydroxypyrroles are obtained by pyrolysis of appropriate aminomethylene Meldrums acid derivatives: the unusual reactions of these compounds with acids, bases, and electrophiles is discussed.

3-Hydroxypyrroles and 1H-pyrrol-3(2H)-ones. Part 13. Reactions of methoxymethylene Meldrum's acid with 3-hydroxypyrroles, with 3-methoxypyrroles and with other active substrates, and pyrolytic heterocyclisations of the products

Methoxymethylene Meldrums acid 2 in acetonitrile solution acts as a useful C-electrophile for active substrates such as pyrrole, indole or tertiary enaminones to give substitution products (e.g.5, 6 or 12, respectively). Primary enaminones react exclusively at the nitrogen atom under these conditions. The effect of ring substituents on the regiochemistry of electrophilic substitution of 3-hydroxypyrroles and 3-methoxypyrroles was studied using methoxymethylene Meldrums acid as the electrophile. Flash vacuum pyrolysis of the Meldrums acid derivatives obtained in many of these reactions gave access to a range of heterocyclic systems, including the pyridone 48, quinolinedione 43, benzazepinedione 41 and fused pyrones 50, 52and 54.

Azepinones. Part 4. Electrocyclic and cycloaddition reactions of simple 1H-azepin-3(2H)-ones

Photolysis of the azepinone (2) gives the bicyclic photoproduct (5) in 64% yield; this compound reverts cleanly to the starting material (2) on thermolysis in toluene. Cycloaddition reactions of the azepinones (1) or (2) with maleic anhydride generate the endo adducts (7) or (8), respectively, whereas treatment of (1) with acetylenic dienophiles gives rise to benzenoid compounds after cleavage of the three-atom bridge.

Azepinones. Part 1. Formation of simple 1H-azepin-3(2H)-ones by gas-phase pyrolysis: crystal and molecular structure of 1-phenyl-1H-azepin-3(2H)-one

Flash vacuum pyrolysis of the Meldrums acid derivatives (4)–(6) at 500 °C (10–3 Torr) gives good yields of the 1H-azepin-3(2H)-ones (7)–(9) respectively. X-Ray crystallography of the 1-phenylazepinone (8) shows that the dienaminone conjugated system is approximately planar though the seven-membered ring as a whole is markedly non-planar. The coalescence temperature for ring-inversion of the 2,2-dimethyl derivative (9) is –96 °C, corresponding to a ΔG‡ of 36.4 kJ mol–1.

3-Hydroxypyrroles and 1H-pyrrol-3(2H)-ones. Part 3. Pyrrolones from pyrolyses of aminomethylene Meldrum's acid derivatives: loss of chirality at the site of hydrogen transfer

Pyrolyses of the diastereoisomeric Meldrums acid derivatives (4) and (5), or of the chiral derivatives (6), (7), and (9), gives 2,2-disubstituted 1H-pyrrol-3(2H)-ones in which there is loss of configuration at the reaction site [e.g.(15) obtained from (9)]. The extent of configuration loss is greater if the reaction site is part of a ring. These results are explained by a two-step, hydrogen-transfer–cyclisation mechanism, following initial generation of a methyleneketene.

3-Hydroxypyrroles and 1H-pyrrol-3(2H)-ones. Part 7. Protonation and O-alkylation of simple 1H-pyrrol-3(2H)-ones: crystal and molecular structure of 3-hydroxy-1-t-butyl-1,2-dihydropyrrolium picrate

O-Protonation of 1H-pyrrol-3(2H)-ones gives cations which are stable indefinitely in solution, and can be isolated as picrate salts. An X-ray crystal structure of the 1-t-butyl derivative confirms charge delocalisation in these cations, which can be regarded as the Wheland intermediates for protonation of 3-hydroxypyrrols. Deuterium exchange at the 2- and 4-position under acidic conditions takes place via the hydroxypyrrole and pyrrolone tautomers, respectively, of the free base. 2,2-Disubstituted 1H-pyrrol-3(2H)-ones are found to give O-alkylated salts on treatment with Meerweins reagent.

On the mechanism of thermal cyclisation of dialkylaminomethyleneketenes to give 1H-pyrrol-3(2H)-one derivatives

The observed loss of optical activity in the pyrrolones (7), (8), and (10) formed by flash vacuum pyrolysis of the chiral substrates (5), (6), and (9) requires that a discrete intermediate is involved in the hydrogen transfer-cyclisation steps which lead to these products.