Abdel Hamid Harhash

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.

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.

Cleavage of azoles—I: Synthesis of some triazolyloxazolines and triazolylbenzoxazones

Abstract Treatment of glycine, and o-aminobenzoic acid with 4-arylhydrazono-2-phenyl-2-oxazolin-5-ones effected the formation of the N-(1,5-diaryl-1H-1,2,4-triazolyl-3-carbonyl) derivatives of the amino acids. The triazolylcarbonylglycines were azlactonised with aromatic aldehydes to 4-arylidene-2-triazolyl-2-oxazolin-5-ones, which behaved similar to the 2-phenyl analogues towards the action of ammonia and amines. Cyclisation of the triazolylcarbonylanthranilic acids with acetic anhydride afforded 2-triazolyl-4H-3,1-benzoxazin-4-ones.

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).

Synthesis of Ethyl α-Phenylthiocarbamylglyoxalate Arylhydrazones and their Reactions with Hydrazines

Treatment of ethyl α-phenylthiocarbamylacetoacetate (1) with aromatic diazonium salts effects acetyl cleavage with the formation of ethyl α-phenylthiocarbamylglyoxalate arylhydrazones derivatives (2 a-e) which afford the anilinopyrazolones (5) and (7) on treatment with hydrazine or phenylhydrazine. The pyrazolones 5 a-e undergo aminoalkylation with formaldehyde and piperidine to give the N-Mannich bases 7 a-e, also obtained by treating the N-hydroxymethyl derivatives (9 a-e) with piperidine.

Synthesis of 2-Methyl-l-phenylthiocarbamoylglyoxal Arylhydrazones and Diethyl(arylazo)(phenylthiocarbamoyl)malonate and their Reactions with Hydrazines

Abstract Treatment of a-phenylthiocarbamoyl acetyl acetone (1) with aromatic diazonium salts effects acetyl cleavage with the formation of 2-methyl-I-phenylthiocarbamoylglyoxal arylhydrazones (2a-c), which afford the anilinopyrazoles (5a-c) and the phenylimino-2- pyrazolines (6a-c) on treatment with hydrazine or phenyl hydrazine respectively. Treatment of diethyl a-phenylthiocarbamoyl malonate with aryl diazonium salts gave diethyl (arylazo)(phenylthiocarbamoyl) malonate which afford the 7-phenyl-5-(arylazo)- 2,3,7-triazabicyclo[3,2,0]hept-I-ene-4,6-dione (9a, b) and its 3-phenyl derivatives (9c, d) with hydrazines and phenyl hydrazine respectively

A Reinvestigation of the Reaction of Salicylideneaniline with Potassium Cyanide

Treatment of salicylidene-anils with potassium cyanide in acetic acid affords 1:1 adducts shown to be the hydrocyano derivatives. When the reaction is conducted in alcohol, salicylidene derivatives of 2-amino-3-arylaminobenzofurans or α-arylamino-o-hydroxyphenylacetamides are formed depending on the molar ratio of the reactants. The formation of the products and the previously reported structures are discussed.