Synthesis of some ethoxyphthalimide derivatives of pyrazoloisoxazoles and pyrazolopyrimidines and their antimicrobial and anticancer screening

Synthesis of 4-arylidene-5-methyl-2,4-dihydro-3H-pyrazol-3-one (IIIa-d) has been achieved by the condensation reaction between 5-methyl-2,4-dihydro-3H-pyrazol-3-one (I) and 4-substituted benzaldehydes (IIa-d). Ethyl acetoacetate and hydrazine hydrate in absolute alcohol undergo cyclization reaction to give (I). 4-Arylidene-5-methyl-2,4-dihydro-3H-pyrazol-3-ones (IIIa-d) have been converted to corresponding ethoxyphthalimide derivatives (IVa-d) by treatment with phthalimidoxyethyl bromide (A). 1-N-Ethoxyphthalimido-3-methyl-4-(4-substituted benzylidene) pyrazol-5-one (IVa-d) has been reacted with hydroxylamine hydrochloride and guanidine nitrate separately to yield ethoxyphthalimide substituted pyrazolo[3,4-c]isoxazoles (Va-d) and pyrazolo[3,4-d]pyrimidines (VIa-d) respectively. All the compounds have been characterized by elemental and spectral analysis mainly IR, 1H NMR and mass spectroscopy. Synthesized compounds have also been screened for various biological activities viz. antibacterial, antifungal, antiviral and anticancer

Synthesis of some ethoxyphthalimide derivatives of pyrazoloisoxazoles and pyrazolopyrimidines and their antimicrobial and anticancer screening

723-731Synthesis of 4-arylidene-5-methyl-2,4-dihydro-3H-pyrazol-3-one (IIIa-d) has been achieved by the condensation reaction between 5-methyl-2,4-dihydro-3H-pyrazol-3-one (I) and 4-substituted benzaldehydes (IIa-d). Ethyl acetoacetate and hydrazine hydrate in absolute alcohol undergo cyclization reaction to give (I). 4-Arylidene-5-methyl-2,4-dihydro-3Hpyrazol- 3-ones (IIIa-d) have been converted to corresponding ethoxyphthalimide derivatives (IVa-d) by treatment with phthalimidoxyethyl bromide (A). 1-N-Ethoxyphthalimido-3-methyl-4-(4-substituted benzylidene) pyrazol-5-one (IVa-d) has been reacted with hydroxylamine hydrochloride and guanidine nitrate separately to yield ethoxyphthalimide substituted pyrazolo[3,4-c]isoxazoles (Va-d) and pyrazolo[3,4-d]pyrimidines (VIa-d) respectively. All the compounds have been characterized by elemental and spectral analysis mainly IR, 1H NMR and mass spectroscopy. Synthesized compounds have also been screened for various biological activities viz. antibacterial, antifungal, antiviral and anticancer

Synthesis and antibacterial evaluation of some theophylline derivatives

2166-2170Some novel antiasthmatic theophylline derivatives have been synthesized and evaluated for biological activity. Oxygen substituted hydroxylamine compounds have been found to possess versatile pharmacological activities. Theophylline N-alkoxy­arylbiguanides 8a-d have been prepared by condensing corres­ponding N-alkoxyamine salt 6a-c with substituted aryldicyan­diamide 7, which in turn is prepared by Gabriel hydrolysis of corresponding alkoxyphthalimides 5a-c. Theophylline is converted to its sodium salt using sodium hydride and treated with bromoalkoxy phthalimide in DMF media. In an another attempt N-allyl theophylline 9 is brominated and condensed with double mole ratio of N-hydroxyphthalimide to obtain 2,3-bis-oxyphthalimido-1-theophylline propane 11. Majority of these compounds have been screened for their antimicrobial activity

Facile synthesis of alkoxyphthalimide derivatized benzimidazole assembled pyrazoles, pyrimidines and isoxazoles, via common intermediate chalcone

1096-1107In the present investigation, synthesis of 2-(3-aryl-2-phenyl-3,4-dihydropyrazol-5-yl)-1-N-alkoxyphthalimidobenzimidazole 9a-h, 4-(1-N-alkoxyphthalimidobenzimidazol-2-yl)-6-arylpyrimidin-2-amine 10a-h and 2-(5-aryl-4,5-dihydroisoxazol-3-yl)-1-N-alkoxyphthalimidobenzimidazole 11a-h are described. Mild dichromate oxidation of 1-benzimidazol-2-yl-ethanol 1 gives 1-benzimidazol-2-yl-ethanone 2 which on Clasien condensation with various aromatic aldehydes yields the corresponding 3-aryl-1-(benzimidazol-2-yl)-prop-2-en-1-one 3a-d derivatives. Compound 3a-d act as key intermediates for all the three series of final compounds. In one pathway 3a-d is converted to its alkoxyphthalimide derivatives 5a-h by condensation with ω-bromoalkoxyphthalimides 4a-b, which cyclize with PhNHNH2/pyridine, guanidine nitrate/10% NaOH and hydroxylamine hydrochloride/CH₃COOH to give 9a-h, 10a-h and 11a-h respectively. In an alternative route, reaction of 3a-d with all the three reagents affords 2-(3-aryl-2-phenyl-3,4-dihydropyrazol-5-yl)benzimidazole 6a-d, 4-(benzimidazol-2-yl)-6-arylpyrimidin-2-amine 7a-d and 2-(5-aryl-4,5-dihydroisoxazol-3-yl)benzimidazole 8a-d which on condensation with ω-bromoalkoxyphthalimides 4a-b give the final compounds 9a-h, 10a-h and 11a-h. Structure elucidations of all the compounds have been accomplished by elemental analysis, IR, ¹H NMR and mass spectral data

Synthesis of alkoxyphthalimide derivatized oxoimidazolidinyl oxazolo/thiazolo dihydropyrimidine and oxoimidazolidinyl tetrahydropyrimidine <i style="mso-bidi-font-style:normal">via</i> common Schiff base intermediate and evaluation of their antibacterial activity

117-127Synthesis of N-(2-(4-substituted phenyl)-3-(2-(1,3-dioxoisoindolin-2-yloxy)ethyl)-5-oxoimidazolidin-1-yl)-3-(2-(1,3-dioxoisoindolin-2-yloxy)ethyl)-6-methyl-2-oxo/thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamides and N-(2-(4-substituted phenyl)-3-(2-(1,3-dioxo-2,3-dihydro-1H-inden-2-yloxy)ethyl)-5-oxoimidazolidin-1-yl)-7-methyl-3-oxo-5-phenyl-3,5-dihydro-2H-oxazolo/thiazolo[3,2-a]pyrimidine-6-carboxamides are described in the present investigation by multistep reactions via common intermediate. 6-methyl-2-oxo/thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate have been prepared by three component Beginelli reaction between benzaldeyde, urea/thiourea and ethyl acetoacetate which is further converted to carbohydrazide derivatives by treating it with hydrazine hydrate. Condensation of with various araldehydes produces the key intermediate N-(4-substituted benzylidene)-6-methyl-2-oxo/thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbohydrazides. Reactions towards route (A) have been carried out by treating it with glycine to afford its imidazolidinone derivatives. Condensation of two replaceable hydrogens with bromoethoxyphthalimide gives the final products. Route (B) have been propagated by reaction of with chloroacetic acid which yields substituted benzylidene)-7-methyl-3-oxo/thioxo-5-phenyl-3,5-dihydro-2<i style="mso-bidi-font-style: normal">H-oxazolo/thiozolo [3,2-a]pyrimidine-6-carbohydrazides. Cyclisation of this with glycine produces imidazolidenone ring derivatives N-(2-(4-substituted phenyl)-5-oxoimidazolidin-1-yl)-7-methyl-3-oxo/thioxo-5-phenyl-3,5-dihydro-2H-oxazolo[3,2-<i style="mso-bidi-font-style: normal">a]pyrimidine-6-carboxamides. Acidic hydrogen of this ring is replaced by ethoxyphthalimide group to give targeted compounds. Structures of synthesized compounds have been confirmed on the basis of chemical tests and spectral studies. Eight compounds have been screened for antibacterial evaluation

Synthesis and characterization of some alkoxyphthalimide derivatives of benzotriazolylthiadiazoles and benzotriazolylthiazolidinones

860-865In the present investigation newer and simple synthetic methods of 5-(1,2,3-benzotriazol-1-yl-methyl)-N-alkoxyphthalimido-1,3,4-thiadiazol-2-amines 5a-b and 2-[(1,2,3-benzotriazolyl)acetohydrazido]-3-N-alkoxyphthalimido-5-arylidene-1,3-thiazolidin-4-ones 9a-h are described. Benzotriazole 1 is converted to carbothioamide 3 by the reaction with ethylchloroacetate followed by thiosemicarbazide. Compound 3 has acted as key intermediate for both series of the final compounds. In one pathway, 3 is converted to corresponding thiadiazole 4 by treatment with Conc. H₂SO₄ and NH₃, which on condensation with ω-bromoalkoxyphthalimide 10a-b gives 5a-b. In an alternative route reaction of 3 with chloroacetic acid and aromatic aldehydes 7a-d has afforded the formation of 2-[(1,2,3-benzotriazolyl)acetohydrazido]-5-arylidene-1,3-thiazolidin-4-ones 8a-d, which are further treated with 10a-b to furnish the final compounds 9a-h. Structural elucidation is accomplished by IR, ¹H NMR and mass spectral data of the synthesized compounds

Research Letter - Evaluation of the antimicrobial activity of some novel alpha substituted hydroxylamine derivatives

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Synthesis of some novel ethoxyphthalimide derivatives of pyrazolo[3,4-c]pyrazoles

1892-1897The synthesis of 5-methyl-4-substituted benzylidene-2,4-dihydro-3H-pyrazol-3-one 3a-d is achieved by the condensation reaction of 5-methyl-2,4-dihydro-3H-pyrazol-3-one 1 with 4-substituted benzaldehydes 2a-d. Compound 1 is prepared by the cyclization reaction between ethylacetoacetate and hydrazine hydrate in absolute alcohol. Compounds 3a-d are converted into corresponding ethoxyphthalimide derivatives 5a-d by treatment with phthalimidoxyethyl bromide 4. 1-N-Ethoxyphthlimido-3-methyl-4-(4-substituted benzylidene)pyrazol-5-ones 5a-d are reacted with thiosemicarbazide/NaOH and isoniazid/AcONa/AcOH separately to yield 6-N-ethoxyphthalimido-4-methyl-3-(4-substituted phenyl)-2-thiocarbamoyl-3,3a-dihydro pyrazolo[3,4-c]pyrazoles 6a-d and 6-N-ethoxyphthalimido-2-isonicotinoyl-4-methyl-3-(4-substituted phenyl)-3,3a-dihydro pyrazolo[3,4-c]pyrazoles 7a-d respectively. Structures of the synthesized compounds have been elucidated by means of IR, 1H NMR and mass spectral data

Synthesis and antimicrobial evaluation of ethoxyphthalimide derivatized spiro [indole-3,5′-(1,3)thiazolo(4,5-<i style="">c</i>)isoxazol]-2(1<i style="">H</i>)-ones <i style="">via</i> ring closure metathesis

368-373The synthesis of 3′-{(4-substituted phenyl-1-N-ethoxy­phthali­mido-6′-pyridin-2-yl}-3,3a′-dihydro-6′H-spiro[indole-3,5′-[1,3]­thi­a­zolo­[4,5-c]­isoxazol]-2(1H)-ones 6a-d is carried out &nbsp;through a five step pathway starting from acid catalyzed condensation of 2-aminopyridine with isatin yielding 3-(pyridin-2-ylimino)-1,3-dihydro-2H-indol-2-one 1 which on reaction with thioacetic acid in the presence of anhydrous ZnCl2 give 3′-pyridin-2-yl-4′H-spiro[indole-3,2′-[1,3]­thiazolidine]-2,4′(1H)-dione 2. Reaction of 2 with various aralde­hydes 3a-d affords the corresponding 5′-[(4-substituted phenyl)­methylidene]-3′-pyridin-2-yl-4′H-spiro­[indole-3,2′-[1,3]­thiazoli­dine]-2,4′(1H)-diones 4a-d. These chal­cones are further cyclised with hydroxylamine hydrochloride to furnish 3′-(4-substituted phenyl)-6′-pyridin-2-yl-3,3a′-dihydro-6′H-spiro[indole-3,5′-[1,3]thia­zolo[4,5-c]isoxazol]-2(1H)-ones 5a-d which are subsequently condensed with ω-bromo­ethoxy­phthalimide to yield the targeted compounds 6a-d. Structural confirmation of the synthesized compounds has been accomplished by IR, 1H NMR, and mass spectral data. Final compounds have been screened for their antimicrobial activity.</b

Synthesis and biological evaluation of 7-N-(<i>n</i>-alkoxyphthalimido)-2-hydroxy-4- aryl-6-aryliminothiazolidino [2,3<i>-b</i>]<i> </i>pyrimidines and related compounds

1306-1313Substituted aryl thioureas 1a-c react with chloroacetic acid in the presence of anhydrous sodium acetate to furnish 2-aryliminothiazolidin-4-ones 2a-c. Condensation of ω-bromoalkoxyphthalimides 3a-c with 2a-c give the corresponding alkoxyphthalimide derivatives of 2-aryliminothiazolidin -4-ones 4a-i. These on condensation with araldehydes 5a-c yield 3-N-(alkoxyphthalimido) -5-arylidene-2-aryliminothiazolidin-4-ones 7a-aʹ. In an alternative route 5a-c react with 2a-c to give 6a-i, which could be cyclised with urea in the presence of sodium acetate to yield the corresponding thiazoli dinopyrimidine 8a-i. 7a-a' are also prepared from 6a-i with 3a-c, which give final compound 9a-a' on cyclisation. Alternatively, 8a-i when condensed with 3a-c also furnish the compounds 9a-a'. Evaluation of antimalarial and antibacterial activity is also reported