Donald Mackay

Decomposition and cycloaddition reactions of some bis(azodicarbonyl) compounds

During oxidation of 1,5-dibenzoylcarbonohydrazide and 1,6-dibenzoyloxalohydrazide with N-bromosuccinimide and pyridine evidence was obtained for the formation of the corresponding bisazo-compounds (4a and b). Both oxidations yielded the oxadiazolone (6), which was the main product in the former. The oxalohydrazide reaction also gave minor products, perhaps attributable to the intermediacy of benzoyldi-imide. Oxidation of 1,7-dibenzoylmalonohydrazide led to intractable mixtures.Oxidation of 1,8-dibenzoylsuccino- and 1,10-dibenzoyladipo-hydrazides and of the bisethoxycarbonyl and dipivaloyl derivatives of terephthalohydrazide gave the fairly stable bisazo-compounds (5a–d) which could be trapped as the meso- and racemic mixture of bisadducts with cyclopentadiene (7a–d). The stereochemical possibilities for the concerted rearrangement of such adducts to bis-1,3,4-oxadiazines are fully discussed. In the adducts (7a and b) only participation of the outer (benzoyl) group and in the ester adduct (7c) only participation of the inner (tetraphthaloyl) group was observed, a diastereomeric pair of structures being produced in each case. The dipivaloyl adduct (7d) showed all three possible modes of isomerisation, utilising both inner and outer acyl groups; one of the pair of diastereoisomers formed was isolated pure in each case.

Evidence for the reaction of nitrosocarbonyl compounds as heterodienes in the Diels–Alder reaction

Evidence is given that a nitrosocarbonyl compound can react with a cyclic diene to give a 5,6-dihydro-1,4,2-dioxazine, not only by isomerisation of an initially formed 2-acyl-3,6-dihydro-1,2-oxazine, but also by reacting as a heterodiene directly with a π-bond in the cyclic diene; the role of the ring oxygen in retarding the isomerisation of an oxazine to a dioxazine is discussed.

Diversity of reaction of azoalkenes in cycloadditions

Reactions of the azoalkenes (E,E)-4-methyl-N-phenyl-2,3-diazapenta-2,4-diene-5-carboxamide 2 and methyl (E,Z)-3-methyl-4-phenylcarbamoyl-1,2-diazabuta-1,3-diene-1-carboxylate 3, having respectively an electron-rich and an electron-poor group on nitrogen, are described. Compound 2, is a stable compound and its stereochemistry was established as E,Eby X-ray crystallography; compound 3 is much less stable and was assigned the E,Z stereochemistry on the basis of its 1H NMR spectrum and the crystal structure of a derivative 17.Of a wide variety of substrates, only azo esters react with 2, which behaves as a heterodiene. The 1,2,3,6-tetra hydro-1,2,3,4-tetrazine 7 obtained from 2 by reaction with dimethyl azodicarboxylate is unstable and on work up yields a 4,5-dihydro-1H-1,2,3-triazole 9a(whose structure was established by X-ray crystallography). This isomerisation is probably acid catalysed since, by inclusion of acid, 7 tautomerises to a 1,2,3,4-tetrahydro-1,2,3,4-tetrazine 8 which then ring contracts to 9a, followed by a decarboxylative elimination of methyl carbamate to yield the 1,2,3-triazole 10.The azoalkene 3 is unreactive to electron-poor substrates, but reacts with cyclopentadiene both as a heterodiene and as a dienophile (at CC) to give as Diels–Alder adducts the tetrahydro-1H-cyclopenta[c]pyridazine 16 and the bicyclo[2.2.1]hept-2-ene 17 respectively. With ethyl vinyl ether 3 gave the ethoxytetrahydropyridazine 18 which eliminated EtOH in acid to the dihydro tautomers 19 and 20 which on basic hydrolysis and oxidation give the pyridazine 21.

A new mode of addition of α-nitrosostyrenes

Treatment of the two known (oxazine)1,4-adducts of α-nitrosostyrene and either 2,5-dimethylfuran or cyclopentadiena with further nitrosostyrene give nitrones, products of 1,3-addition at the oximion CN.

Cyclopentadienone oxime dimers as precursors to cyclone equivalents

Monomerisation (110–150 °C) of the stereoisomeric mixture of the dioxime 6a, or its ethers or esters, 6b–e, gives the oximes 7 which can be trapped by a wide range of dienophiles to give good yields of the adducts 8–12; deoximation of these to the ketones can be effected by catalytic hydrogen transfer (Pd/C, cyclohexadiene) as a mild alternative to acid hydrolysis.

Pentacyclic cage formation in the intramolecular [3 + 2]addition of tricyclic nitrones

Despite their anti-configurations three tricyclic nitrones, on heating in toluene, undergo high-yield [3 + 2] intramolecular addition to give the corresponding pentacyclic cages; a co-product from heating two of the nitrones in tetrachloroehylene is the pyridyl ketone.

The reaction of nitrosocarbonyl compounds with 2,5-disubstituted furans. Synthesis of 1,4,2-dioxazine and 1,4,2-dioxazole derivatives

Oxidation of hydroxamic acids at room temperature in the presence of 2,5-dimethylfuran gives cis-1,4,2-dioxazolylbutenones (5), the structures of which have been confirmed by the synthesis of the dihydro-derivative (12) from the reaction of benzonitrile oxide with hexane-2,5-dione. If the oxidation is carried out at 0 °C good yields of the unstable furo[1,4,2]dioxazines (7), the formal products of the addition of the furan to the nitrosocarbonyl-arene or -alkane, can be isolated. Compounds (7) are the precursors to (5) and this isomerisation in the oxidation medium is essentially quantitative. It is probably catalysed by an unidentified component, since when pre-isolated (7) is heated the reaction is solvent-dependent and sometimes complex, the amounts of (5) formed being very variable. Nitrosocarbonylbenzene adds to the unsymmetrical compound 2-methyl-5-phenylfuran only at the 2,3-bond, giving the dioxazine (17) and thence the dioxazole (15) exclusively. Secondary amines add readily to the β-carbon of the enone group in (5) while tertiary amines, or more efficiently iodine, convert (5) into the trans-isomers (11)The retro-reaction of (5c) at 80 °C to dimethylfuran and p-nitronitrosocarbonylbenzene has been demonstrated by trapping the latter, with 1,4-dimethyl-2,3-diphenylcyclopentadiene, as the adduct (21).

Competitive [4 + 2] and [3 + 2] cycloadditions of nitrosoalkenes to the imino bond of bicyclic 1,2-oxazines

The bicyclic 1,2-oxazines derived from the cycloaddition of α-nitrosostyrene to either 2,5-dimethyl-furan (11) or cyclopentadiene (15) react further with nitrosostyrene or other nitrosoalkenes. Only 3 + 2 addition is observed with (11) to give the tricyclic nitrones (12) and (13), shown by X-ray analysis of (12) to be cis-anti-cis fused, with a central boat conformation. The adduct (15) gives both nitrones (16)–(18) and the 4 + 2 cycloadducts of the 1,2,5 oxadiazines (21)–(23). The latter mode of addition is favoured by nitrosoalkenes with electron withdrawing α-substituents. The oxadiazine (23), derived from 3-nitrosobut-3-en-2-one is cis-syn-cis fused with a central chair conformation in the crystal state, but exists in solution in equilibrium with a small amount of the boat conformation.The requirements for addition to the imino bond are demanding, many other model systems related to (11) or (15) failing to react.

Anomalous shielding and hidden partner chemical exchange in the 1H NMR spectra of the bisurethane diazetidines, the 1,2-diaryl-3,5-dialkyl-6,7-dialkoxycarbonyl-4-oxo-6,7-diazabicyclo [3.2.0]hept-2-enes

The bicyclic diazetidines (3), (11), and (17), have trans-pyramidal nitrogens, the ester group on N(7) being sterically protected and very unreactive. Its alkyl group is close to the face of the aryl ring attached to C(1) and shows remarkable shielding effects in its 1H NMR spectrum, while the alkyl group of the N(6) ester shows a more normal resonance. In the methyl esters the OMe group of the N(7) ester is ca. 1 ppm upfield of the other ester OMe group and in each of the oxymethylene compounds one of the protons of the N(7) ester group is upfield of its (unshielded) diastereotopic partner by ca. 2 ppm.These shielded resonances are extremely broadened at room temperature, especially at high field. DNMR studies show that on cooling, the shielded absorption in each case broadens further and then sharpens into two peaks, an effect due to the interconversion of two major conformations with one or more of very low population, an example of ‘hidden partner exchange.’ The exchange processes responsible, which occur between protons in the N(7) ester group in very shielded (major conformations) and normal (minor) environments, must involve either N(7) inversion or N(7)–CO rotation.The di-methyl and -trichloroethyl compounds (3a) and (3c), were investigated in detail in CD2Cl2 and C7D8. In (3a) the N(7) ester OMe resonance of the minor partner was found at δ 3.65 (ca. 3%, 200 K, CD2Cl2), its identity being confirmed by low-temperature examination of the deuteriated isomers (20) and (21). In (3c) there are two minor conformations, ca. 2% each.Two major and at least one minor conformation were observed for the dibenzyl and dimethyl esters (3d) and (11); the latter also showed a very shielded Me in the ring C(5) ethyl group. The presence of a minor conformation was not conclusively detected in the diethyl ester (3b), but was inferred from the broadening of the upfield signals of its two major conformations. The acecylcone derived compound (17) showed three major conformations (46 : 36 : 18%), the second and third together (unresolved) being the most shielded in the N(7) group, though less so than in the other diazetidines.Rotation of the C(1) Ph ring has also been identified as a conformational process in all the diazetidines [except (17)] but is quite independent of the processes leading to anomalous shielding of the ester groups.

1,4,2-Dioxazole synthesis by the reaction of nitrosocarbonyl compounds with 2,5-dimethylfuran

Oxidation of hydroxamic acids in the presence of 2,5-dimethylfuran gives excellent yields of the 3-substituted-5-methyl-5-(cis-3-oxobutenyl)-1,4,2-dioxazoles (2); the reaction is reversible and probably occurs by way of an initially formed Diels–Alder adduct.