Nehal M. Elwan

Synthesis of [1,2,4]triazolo[3,4-a]isoquinolines and pyrrolo[2,1-a]isoquinolines using α-keto hydrazonoyl halides

Abstract Treatment of α-keto hydrazonoyl halides 1 with 3,4-dihydro-6,7-dimethoxyisoquinoline 3 and its 1-methyl derivative 4 in the presence of triethylamine in tetrahydrofuran at reflux afforded the corresponding cycloadducts 6 and 9 , respectively. The same halides 1 react with 1-cyanomethyl-3,4-dihydro-6,7-dimethoxyisoquinoline 5 and afforded pyrrolo[2,1-a]isoquinoline derivatives 12 in high yield.

Synthesis and Reactivity of 2-(6,7-Diethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile towards Hydrazonoyl Halides

The synthesis of 2-(6,7-diethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile (1) has been performed by ring closure of the corresponding amide according to the Bischler-Napieralski method (Scheme 1). Based on spectroscopic data, the tautomeric 2-(tetrahydroisoquinolin-1-ylidene)acetonitrile is the actual compound. The reactions of 1 with alpha-oxohydrazonoyl halides 4 in the presence of Et3N led to 2-(aryldiazenyl)pyrrolo[2,1-a]isoquinoline derivatives 8 (Scheme 2), whereas with C-(ethoxycarbonyl)hydrazonoyl chlorides 14, 2-(arylhydrazono)pyrrolo[2,1-a]isoquinoline-1-carbonitriles 16 were formed (Scheme 4). The structures of the products were established from their analytical and spectroscopic data and, in the case of 8b, by X-ray crystallography.

NOVEL SYNTHESIS OF 4,5-DIHYDROSPIROPYRAZOLE- 5,2′-INDANE-1′,3′-DIONES

ABSTRACT A novel synthesis of 4,5-dihydrospiropyrazole-5,2′-indane- 1′,3′-diones 7a–n, 8a–c,e,f and 12a–f via the treatment of hydrazonoyl halides 1–3 with 2-arylidene indane-1,3-diones 6a–e respectively, is reported.

New Routes to Fused Isoquinolines

Treatment of 6,7-diethoxy-3,4-dihydroisoquinoline (8) and its 1-methyl derivative 12 with hydrazonoyl halides 10 in the presence of Et3N in THF under reflux afforded the corresponding 5,6-dihydro-1,2,4-triazolo[3,4-a]isoquinolines 11 and 13, respectively, in high yield (Schemes 2 and 3). The products are formed via regioselective 1,3-dipolar cycloaddition of the intermediate nitrilimines 9 with the isoquinoline C=N bond. Reaction of 6,7-diethoxy-3,4-dihydroisoquinoline-1-acetonitrile (4a) with ethyl alpha-cyanocinnamates 15 in the presence of piperidine in refluxing MeCN yielded benzo[a]quinolizin-4-ones 16 (Scheme 4). Under the same conditions, 12 and arylidene malononitriles 19 reacted to give benzo[a]quinolizin-4-imines 20 (Scheme 5). Instead of 15 and 19, mixtures of an aromatic aldehyde, and ethyl cyanoacetate or malononitrile, respectively, can be used in a one-pot reaction.

Synthesis of 3,3‘-bipyrazole, 5,5‘-bi-1,3,4-thiadiazole and fused azole systems via bishydrazonoyl chlorides

A number of novel 3,3′-bi-pyrazole, 5,5′-bi-1,3,4-thiadiazole and azolothiazole derivatives were synthesised via cycloadditions of bis-hydrazonoyl chlorides with olefin, active methylene, and thioacetanilide synthons.

Synthesis of C-(2-furyl)-N-(4-nitrophenyl)methanohydrazonyl bromide. Reactions with nucleophiles and active methylene compounds

Synthesis of C-(2-furyl)-N-(4-nitrophenyl)methanohydrazonyl bromide2 is described. Treatment of2 with nucleophiles affords the corresponding substitution products3–7. Also, compound2 reacts with selenocyanate anion and thiocyanate anion and give the corresponding selenadiazoline and thiadiazoline8 and9, respectively. Moreover, reaction of2 with enolates of various active methylene compounds afforded the pyrazole derivatives17–20.

Synthesis and cycloaddition reactions of N-phenyl-C-styrylmethanohydrazonyl bromide

N-Phenyl-C-styrylnitrilimine (I) reacts with arylidenesulphonylacetonitriles or arylidenemalononitriles to give exclusively 5-cyanopyrazoles. On the other hand cycloaddition of ethyl arylidenecyanoacetate, α-cyanoarylideneacetophenones and benzylidene α-cynoacetanilide with I yields 2-pyrazoline derivatives. Also, nitrilimine I reacts with N-arylmaleimides to give the corresponding pyrrolopyrazoles

Regioselective synthesis of [1]benzopyrano[4,3-c]pyrazol-4-(1H)-one and [1]benzopyrano[3,4-c]pyrazol-4(3H)-one derivatives

The cycloaddition reaction of N-phenyl-C-cinnamonitrilimine4 to coumarin leads to the formation of 3-styrylbenzopyrano[4,3-c]pyrazole derivative6, whereas 3-phenylsulfonylcoumarin 0163 0181 V 39 or 3-bromocoumarin10 or 3-cyanocoumarin11 gives 1-styrylbenzopyrano[3,4-c]pyrazole derivative7. Also, the cycloaddition of4 to 3-acetylcoumarin15 and 3-benzoylcoumarin16 gives the corresponding dihydropyrano[3,4-c]pyrazole adducts17 and18 respectively. Oxidation of17 and18 gives7.

Synthesis and cycloaddition reactions of C-(2-Naphthoyl)-N-arylmethanohydrazonoylpyridinium bromides

Coupling of naphthacylpyridinium bromide2 [1-(2-naphthyl) ethanone-2-pyridinium bromide] with N-nitrosoacetarylamides afforded C-(2-naphthoyl)-N-arylmetha-nohydrazonoylpyridinium bromides3A-C. Treatment of3A-C with base afforded the corresponding tetrazines6A-C. Cycloaddition of nitrilimines5A-C to N-arylmaleimides, acrylonitrile, ethyl acrylate, acrylamide, fumaronitrile, α-cyanocinnamonitriles, ethyl α-cyanop-nitrocinnamates and α-cyano-p-nitrocinnamamide afforded the corresponding cycloadducts7–14, respectively. The cycloadducts11–14 undergo a facile thermal elimination of hydrogen cyanide to give the corresponding pyrazoles18–21, respectively.

Kinetics and Mechanism of Dehydrochlorination ofN-Aryl 2-Oxo-2-phenylaminoethanehydrazonoyl Chloridesand their Mass Spectra

The dehydrochlorination mechanism of the titlecompounds in solution and inside a mass spectrometer isstudied.