W. Asker

Reactions with 1(2H)-phthalazinones, 4,5-dihydro-3(2H)-pyridazinones and 3-pyrazolin-5-ones

Abstract The condensation of 1(2H)-phthalazinones (Ia-c), 4,5-dihydro-6-phenyl-3(2H)-pyridazinone (IIIa), and 4-arylidene-4,5-dihydro-6-phenylpyridazinones (IVa-b) with secondary amines and formaldehyde yields the corresponding N-Mannich-bases (Id, IIIc-d, and IVi-j, respectively). Similarly, reaction with acrylonitrile, affords the cyanoethylated products (Ig, IIIf, and IVk-1, respectively). The Mannich-bases (Id) are also obtained by reaction of the appropriate amines with the corresponding chloromethyl- (If), or hydroxymethylphthalazinone derivatives (Ie); and by treatment of the hydroxymethyl derivative of IIIa with the same reagents. In the presence of ethyl-amine, the condensation of la-c with formaldehyde yields the corresponding bis-derivatives (II). The reaction of 3-methyl-2-phenyl-3-pyrazolin-5-one (Va) with formaldehyde and piperidine or morpholine involves the hydrogen atom on C 4 with formation of the Mannich-bases (Vd-e). In addition, the synthesis of some of the corresponding bis-derivati es (VI) are reported. The IR spectra of the reaction products are discussed. Interaction of Vd with aromatic thiols leads to the formation of 4-arylthiomethyl-3-methyl-2-phenyl-3-pyrozolin-5-ones (IVf-i). The latter compounds react with ethereal diazomethane yielding products believed to have structures similar to VII. Treatment of 2-N-piperidinomethyl-4-phenyl-1(2H)-phthalazinone (cf. Id), and 2-N-piperidino-methyl-6-phenyl-4,5-dihydro-3(2H)-pyridazinone (IIIe) with phenylmagnesium bromide, followed by hydrolysis, gives 1,4-diphenylphthalazine and 3,6-diphenylpyridazine (VIII), respectively. The latter has also been obtained by the action of the same reagent on IIIa and/or 6-phenyl-3(2H)-pyridazinone.

Reactivity of unsaturated centres in heterocycles and chalkones toward diazoalkanes

Abstract Treatment of 4-arylidene derivatives of five-membered heterocycles with diazomethane results in cyclopropane formation; C-alkylation has been observed in the case of 4-ethylidene-2-phenyl-5-(4H)-oxazolone. Δ2-Pyrazolines have been obtained via the action of diazomethane on a number of newly prepared chalkones; cyclopropane formation is proved in the case of piperonylidene-5-acetoacenaphthene. Methylation of 4-arylazo derivatives of a number of five-membered heterocycles is discussed.

Synthesis of substituted linear furano[2,3-g][1]benzopyrones and [3,2-b]thianaphtenopyrones

Abstract The synthesis of the linear foranopyrones: 2,3-diphenyl-8-hydroxy-6H-furano[2,3=g][1]-benzopyran-6-one (I) and 2,3-diphenyl-6-methy;-8H-furano[2,3-g][1]benzopyran-8-one (II) is described. Hetero-oxygen-ring opening in 4-hydroxy-2-oxo-2H-pyrano[3,2-b]thianaphthene (IVa) has been accomplished by the action of aromatic amines. Treatment of the new 3-acyl-4-hydroxy-2-oxo-2H-pyrano[3,2-b]thianaphthenes (IVb–d) with amines yielded the corresponding amino or imino compounds (VIIa–f). Synthesis of the new 2-aryl-4-oxo-4H-pyrano[3,2-b]thianaphthenes (Xa–c) is described. The β-sulfides (XIa–k) have been obtained via the addition of the appropriate thiols to the chalcones (IXa–f). 2-Cinnamoyl-3-hydroxythianaphthene 1,1-dioxides (XIIa–b) form labile adducts with thiols.

Cleavage reactions with 4-substituted isoxazolin-5-ones

Abstract The exocyclic double bond in 4-arylidene-3-methylisoxazolin-5-ones (IV) undergoes addition reactions with Grignard reagents and with aromatic hydrocarbons in the presence of aluminium chloride. The behaviour of the hetero-ring in 4-substituted 3-methylisoxazolin-5-ones towards the action of hydrazines has been investigated. Whereas, the corresponding pyrazolines (X) are obtained in the case of hydrazine hydrate, the intermediate hydrazides (XI) have been successfully isolated in the case of phenylhydrazine. The hydrazides are readily cyclized under different experimental conditions to yield different products.

Behaviour of the hetero-ring in substituted 2-phenylimino-4-thiazolidinones towards the action of organomagnesium compounds

Abstract Treatment of 5-arylidene derivatives of 2-phenylimino-4-thiazolidinones with Grignard reagents does not open the hetero-ring, the double bond of the lateral chain, the CC bond and the CN bond of Ic, enter into reaction, yielding colourless products, believed to have structure III. On the other hand, 5-benzylidene-3-phenyl-2-phenylimino-4-thiazolidinone (Id) on treatment with Ph Mg Br undergoes addition to the CC bond of the lateral chain with the formation of 5-diphenylmethyl-3-phenyl-2-phenylimino-4-thiazolidinone (IIc). Whereas, the Grignard reagents do not attack the carbonyl group of the thiazolidine ring in Ic and Id, the carbonyl group in 5-methyl-2-phenylimino-4-thiazolidinone undergoes 1,2-addition with Ph Mg Br, followed by loss of water upon hydrolysis of the reaction mixture to yield Va. Elucidation of the structure of the latter has been proved by an independent synthesis. Hetero-ring opening by the action of Ph Mg Br in the thiazolidine system, has been found upon treatment of 5-methyl-3-phenyl-2-phenylimino-4-thiazolidinone with the same reagent, yielding N,N′-diphenylbenzamidine. The discrepancy in the melting points of the 5-arylidene derivatives of 2-phenylimino-4-thiazolidinone and of 3-phenyl-2-phenylimino-4-thiazolidinone is discussed.

Reactions with 4-substituted isoxazolin-5-ones—II☆

Abstract The exocyclic double bond in 4-arylidene-3-substituted-isoxazolin-5-one (I) undergoes addition reactions with Grignard reagents and with benzene in the presence of aluminium chloride. Treatment of 4-arylazo derivatives of 3-substituted-isoxazolin-5-ones (III) with Grignard reagents does not effect hetero-ring opening and only the carbonyl group of III enters into reaction, followed by elimination of the elements of water on acidifcation, yielding 3-substituted-4-arylazo-5-arylisoxazoles (IV). Deacylation of 4-acetyl-3-phenylisoxazoline-5-one (VI) is achieved by the action of organomagnesium compounds, magnesium-magnesium iodide mixture, and/or lithium aluminium hydride. 3,4-Disubstituted-5-methoxyisoxazoles (X) are readily obtained upon treatment of II with diazomethane. 2-Methyl-3,4-disubstituted-isoxazolin-5-one (XI) are produced via the action of methyl iodide on the silver salt of II and/or via the action of dimethyl sulphate on IIa directly.

Reactions with 1,2,3-trione-2-arylhydrazones

Abstract Whereas, the pentan-2,3,4-trione-3-arylhydrazones (IVa–d) and 1-phenylbutan-1,2,3-trione-2-arylhydrazones (Va–d) undergo the Mannich reaction with formaldehyde and piperdine, 1,3-diphenylpropan-1,2,3-trione-2-arylhydrazones (VIa–d) are recovered unchanged. The ease of cleavage of the acetyl group during the reaction is stressed. A number of the Mannich-bases (VII) react with aromatic thiols to yield the corresponding sulphur analogues (VIII). The arylhydrazones of the triones (IV–VI) undergo 1,2-addition of the Grignard reagent, to the acetyl carbonyl group in IV and V and to the benzoyl carbonyl group in VI, to yield Za–k. Acetophenone is obtained upon chromic acid oxidation of Xa–b; on the otherhand, benzophenone is obtained in the case of Xd. Treatment of Xh and Xj with hydrazine hydrate eliminates the tertiary carbinol moiety with the formation of the hydrazones of the corresponding phenylglyoxal arylhydrazones (XIa–b).