Synthesis and cycloaddition reactions of 4,4-dimethyl-2,6-dioxocyclohexane-thiocarboxamides with nitrilimines

Hamdi M Hassaneen,Fatma M Saleh,Ahmad S Shawali,Tayseer A Abdallah

doi:10.3998/ark.5550190.p008.855

Hamdi M Hassaneen, Fatma M Saleh + Show 2 more

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https://doi.org/10.3998/ark.5550190.p008.855

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Abstract

A new series of 4,4-dimethyl-2,6-dioxocyclohexane-thiocarboxamides were prepared by reaction of aryl isothiocyanate with dimedone. Reaction of N-aryl-4,4-dimethyl-2,6-dioxocyclohexane- thiocarboxamides with hydrazonoyl halides led to th e formation of the corresponding thiadiazoles. Treatment of 2-(5-acetyl-3-phenyl-1,3 ,4-thiadiazol-2(3 H)-ylidene)-5,5- dimethylcyclohexane-1,3-dione with dimethylformamide dimethylacetal (DMF-DMA) in refluxing dioxane afforded (E)-2-(5-(3-(dimethylamino)acryloyl)-3-phenyl-1,3,4-t hiadiazol- 2(3H)-ylidene)-5,5-dimethylcyclohexane-1,3-dione. Reaction of the latter enaminone with hydrazonoyl halides yielded the corresponding 2-(1- aryl-3-substituted-pyrazol-4-carbonyl)-5-(3- phenyl-5-(5,5-dimethylcyclohexane-1,3-dione)-(1,3,4)-thiadiazole) derivatives. The structures of the new compounds were elucidated on the basis of t heir elemental analyses and spectral data.

Highlights

In the light of these activities and in continuation of our work dealing with chemistry of hydrazonoyl halides,1-20 it was thought interesting to synthesize new functionalized 1,3,4-thiadiazole derivatives and evaluate their pharmaceutical activities
The synthetic strategy adopted for the target compounds is based on reactions of hydrazonoyl halides with 4,4-dimethyl-2,6-dioxocyclohexane-thiocarboxamides 3 (Scheme 1)
Such reactions have not been reported hitherto. Our interest in such a study is to shed some light on the site selectivity in the target cycloaddition reactions of nitrilimines to 3 as the latter compounds contain three dipolarophilic sites namely C=O, C=C and C=S groups

Summary

Introduction

A literature survey revealed that many substituted 1,3,4-thiadiazole derivatives exhibit wide range of biological activities such as antimicrobial, antituberculosis, antiviral, anti-inflammatory, anticancer, antidiabetic and anticonvulsant activities. In the light of these activities and in continuation of our work dealing with chemistry of hydrazonoyl halides, it was thought interesting to synthesize new functionalized 1,3,4-thiadiazole derivatives and evaluate their pharmaceutical activities. In the light of these activities and in continuation of our work dealing with chemistry of hydrazonoyl halides, it was thought interesting to synthesize new functionalized 1,3,4-thiadiazole derivatives and evaluate their pharmaceutical activities. The synthetic strategy adopted for the target compounds is based on reactions of hydrazonoyl halides with 4,4-dimethyl-2,6-dioxocyclohexane-thiocarboxamides 3 (Scheme 1). Such reactions have not been reported hitherto. Our interest in such a study is to shed some light on the site selectivity in the target cycloaddition reactions of nitrilimines to 3 as the latter compounds contain three dipolarophilic sites namely C=O, C=C and C=S groups

Results and Discussion

Me Me

Experimental Section