Condensation Of 2a Research Articles

Design, synthesis, DNA assessment and molecular docking study of novel 2-(pyridin-2-ylimino)thiazolidin-4-one derivatives as potent antifungal agents

A series of novel 2-imino-4-thiazolidinone derivatives 4a,b was synthesized through reaction of unsymmetrical thioureas 3a,b with chloroacetic acid. Condensation of 4a,b with aromatic aldehydes 5a-eyielded the corresponding 5-arylidene derivatives 6a-j. In addition, the reaction of 4a,b with 4-arylazo-3-hydroxybenzaldehydes 8a-c furnished the respective mono-arylazo-4-thiazolidinones10a-f. All the newly synthesized compounds were confirmed by their elemental analysis and spectral data. The antifungal activity of the newly synthesized compounds was assessed and the compounds 6d, 6e, 6i, 6j, 9a,b and 10a-frevealedhigher antifungal activity towards Alternaria solani than to the standard Ridomil gold plus. Moreover, the DNA toxicity of 4-thiazolidinone derivatives 6d, 9a, 10b, 10c and 10f on the nucleic acid of Alternaria solani (KT354939) was performed and the results showed qualitatively more than 70% cleavage. Also, compounds 6i, 6j, 9b, 10c and 10f were docked inside the active site of 1ZOYenzyme and suitable binding with the active site of amino acids, were displayed according to their bond lengths, angles and conformational energy.

-Oxo anilides in Heterocyclic Synthesis: Novel Synthesis of Pyridazinones, Pyrazolopyridazines, and Cinnolines

Compound 1 coupled smoothly with aromatic diazonium salts to yield the corresponding arylhydrazones 2a-d. Compounds 2a-d condensed with DMF-DMA in refluxing xylene to yield the pyridazinones 3a-d. Compounds 3a-d were also established based on its further reaction with some active methylene reagents and some nucleophilic reagents. So, reactions of 3a, b with malononitrile in refluxing ethanolic piperidine afforded arylidinemalononitrile 4a,b. The pyridazinone derivatives 3a, b reacted with hydrazine hydrate to afford the hydrazine derivatives 5a, b. When 3a,b were fused with hydrazine hydrate without solvent, the pyrazolo[4,3-c]-pyridazines 6a,b were obtained. Compounds 6a, b were also obtained when compounds 5a, b melt over melting point for short time. Condensation of 2a, b with ethyl cyanoacetate yield 7a, b. Similarly, reactions of 2a,b with 1 mole of malononitrile afforded the pyridazine derivatives 8a,b. While, when 2 moles of malononitrile reacted with 2a, b in the same experimental conditions to yield the cinnoline derivative (9a, b). Reactions of pyridazine 8a,b with 1 mole of malononitrile afforded 9. Compound 2b was reacted with a mixture of arylidinemalononitrile and acrylonitrile to yield product formulated as triazole moieties 12a, b. Similarly, compound 2b was reacted with a mixture of maleic anhydride and acrylonitrile in the same above experimental conditions to give 13. Also, reactions of 2b with hydroxylamine hydrochloride yield 14.

Synthesis of some novel pyrazolo[1,5-a]quinazolines and their fused derivatives

ABSTRACTNew pyrazolo[1,5-a]quinazoline-3-carbonitriles 4a,b were obtained via cyclocondensation of 5-amino-3-cyanomethyl-1H-pyrazole-4-carbonitrile (1) with enaminones of 1,3-cyclohexanedione derivatives 2a,b in refluxing glacial acetic acid. Condensation of compounds 4a,b with various aromatic aldehydes furnished the corresponding arylidene derivatives 6a–j. On the other hand, condensation of 4a,b with o-hydroxybenzaldehydes yielded the polyheterocyclic compounds 10a–h. Coupling of compounds 4a,b with aryldiazonium chlorides led to formation of 2-arylhydrazono derivatives 12a–h. Also, reaction of compounds 4a,b with phenyl isothiocyanate, followed by addition of ethyl chloroacetate and chloroacetonitrile, afforded the polyheterocyclic compounds based on pyrazolo[1,5-a]quinazoline core. The reaction of compounds 4a,b with phenyl isothiocyanate and elemental sulfur gave the thiazole-2-thione derivatives 25a,b. The reaction of enamines of compounds 4a,b with each of hydrazine hydrate and guanidine hydrochloride afforded pyrazolo[4″,3″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-a]quinazolin-8-ones 30a,b and pyrimido[5″,4″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-a]quinazolin-9(10H)-ones 33a,b, respectively. The structures of all the newly synthesized compounds were elucidated by elemental analyses and spectral data. The plausible mechanisms have been postulated to account for their formation.

New Potent SARS-CoV 3C-Like Protease Inhibitors Derived from Thieno[2,3-d]-pyrimidine Derivatives.

2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1) condensed with carbaldehydes 2a,b to give the respective thienopyrimidines (3a,b), which reacted with phosphoryl chloride and hydrazine hydrate to afford the respective pyrimidinohydrazines (4a,b). Compound 4a condensed with acetophenone under Vilsmeier conditions to afford the formylated pyrazolopyrimidine 6. Condensation of 4a with active methylenes produced the respective pyrazolopyrimidines (7-11). Besides, 4a condensed with succinic anhydride and with phthalic anhydride, yielding the pyrrolidine-2,5-dione 12 and the isoindoline-1,3-dione 13, respectively. Moreover, 4a reacted with isatin to afford the hydrazono-indolin-2-one 14. Structural elucidations for the new thienopyrimidines were based upon compatible analytical and spectroscopic results. Eleven of the new compounds were tested and found active against influenza A neuraminidase virus (H3N2). Compounds 12 and 13 were the most potent.

Synthesis of Benzoxazolylthiomethyl and Benzthiazolylthiomethyl Quinazolin-4(3h)-ones

GRAPHICAL ABSTRACT

ChemInform Abstract: Synthesis and Protonation Behavior of 26-Membered Oxaaza and Polyaza Macrocycles Containing Two Heteroaromatic Units of 3,5-Disubstituted Pyrazole or 1-Benzylpyrazole. A Potentiometric and 1H and 13C NMR Study.

The synthesis and acid−base behavior of two series of 26-membered dioxatetraamine and hexaamine heterocyclophanes containing two nuclei of either pyrazole (4a and 6a) or 1-benzylpyrazole (4b and 6b), respectively, are reported. Dipodal (2 + 2) condensations of 3,5-pyrazoledicarbaldehyde 2a or its 1-benzyl derivative 2b with 1,5-diamino-3-oxapentane afford in both cases the stable Schiff bases 3a,b in 90% yield, which after reduction with NaBH4 gave 4a,b in 75% and 84% yield, respectively. Condensation of 2a with diethylenetriamine leads to a complex mixture containing imidazolidine isomers, which was reduced in situ to afford 6a in 30% yield. Condensation of 2b with the same amine gave the stable diimidazolidine derivative 5b, which after crystallization was isolated as a pure compound in 80% yield and fully identified from analytical and 1H and 13C NMR data as a constitutional isomer with both imidazolidine rings located at the side of the pyrazole closer to the benzylic substituents. Reduction of 5b wit...

SYNTHESIS OF NEW 4(3H)-QUINAZOLINONE DERIVATIVES OF POTENTIAL ANTIMICROBIAL ACTIVITY

A new series of quinazoline-4(3H)-one derivatives containing hydrazone, thiosemicarbazide, pyrazole moiety and 1,2,4triazolo[4,3-a]quinazolin-5-(4H)-one derivatives, were prepared in order to study the effect of such combinations on the expected antimicrobial activity. Synthesis of target compounds (3-8) has been achieved through an interaction of the starting 2a or 2b with different alkyl or aryl isothiocyanate. Condensation of 2a or 2b with various aromatic aldehydes or ketones afforded the corresponding hydrazones 9-12. 1-(4-Pyridinyl)-1,2-dihydro-4phenyl(allyl)-1,2,4-triazolo[4,3-a]quinazolin-5-(4H)-one deriva tives 13, 14 have been synthesized through reflux of compound 9 or 10 in glacial acetic acid. On the other hand, 1-(3-substituted-3,4dihydro-4-quinazolinon-2-yl)-3-(4-chlorophenyl) pyrazole-4-carbaldehyde 15 or 16 has also been synthesized through interaction of compounds 11 or 12 with Vilsmeier-Haack reagent1. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their in vitro antibacterial and antifungal activities. The tested compounds showed moderate antibacterial activity and weak or no antifungal activity.

Substituted Hydrazonals as Building Blocks in Heterocyclic Synthesis: A New Route to Arylhydrazonocinnolines

2-heteroylhydrazonopropanals 2a–e and 3-oxo-2-arylhydrazonopropanals 2f–k were prepared via coupling of enaminones 1 with aromatic diazonium salts. Compounds 2a–c condensed with hydrazine hydrate to yield the corresponding hydrazones 3a–c which afford on cyclisation the cinnoline derivatives 6a–c, while condensation of 2g, j with hydrazine hydrate directly yielded the pyrazole derivatives 4g–j. Condensation of 2a–c, f, g with phenyl hydrazine gave the corresponding phenyl hydrazone derivatives 7a–c, f, g. Structures of 2a, h and 3a were assessed by single crystal X-ray analyses.

Mononuclear and Heterodinuclear Metal Complexes of Nonsymmetric Ditertiary Phosphanes Derived from R2PCH2OH

AbstractThe new nonsymmetric ditertiary phosphanes, Ph2PCH2N(R)CH2PAd [3a: R = C6H5, 3b: R = C6H4(4‐CH3)] were prepared using a three‐step sequence of condensation reactions. Hence treatment of AdP‐H (AdP‐H = 1,3,5,7‐tetramethyl‐2,4,8‐trioxa‐6‐phosphaadamantane) with (CH2O)n at 110 °C gave the adamantane‐derived hydroxymethylphosphane 1, which upon condensation with C6H5NH2 or C6H4(4‐CH3)NH2 gave the secondary aminophosphanes HN(R)CH2PAd [2a: R = C6H5, 2b: R = C6H4(4‐CH3)]. Further condensation of 2a or 2b with Ph2PCH2OH gave 3a or 3b in high yields (ca. 85 %) containing the sterically encumbered adamantane cage. The coordination capabilities of 2a, 3a and 3b have been explored with various PdII, PtII, RuII, IrIII and AuI metal centres. Bridge cleavage of {Pd(κ2‐C,N‐C16H16N)Br}2 with 2 equiv. of 2a gave the neutral, mononuclear complex Pd(κ2‐C,N‐C16H16N)Br(2a) (4). Reaction of 3a/3b with MCl2(cod) (M = Pt, Pd) gave the corresponding κ2‐P,P′‐chelate complexes cis‐MCl2(3) [5a: M = Pt, R = C6H5, 5b: Pt, R = C6H4(4‐CH3), 5c: Pd, R = C6H5, 5d: Pd, R = C6H4(4‐CH3)]. In contrast, bridge cleavage of the dimers {RuCl2(η6‐p‐cym)}2 or {IrCl2(η5‐Cp*)}2 with 3a gave the κ1‐P‐monodentate complexes RuCl2(η6‐p‐cym)(3a) (6) and IrCl2(η5‐Cp*)(3a) (7), respectively, in which the –PAd group is noncoordinating. Reaction of 6 or 7 with AuCl(tht) (tht = tetrahydrothiophene) gave the mixed‐metal complexes κ2‐P,P′‐μ‐RuCl2(η6‐p‐cym){Ph2PCH2N(Ph)CH2PAd(AuCl)} (8) and κ2‐P,P′‐μ‐IrCl2(η5‐Cp*){Ph2PCH2N(Ph)CH2PAd(AuCl)} (9). All new compounds have been fully characterised by spectroscopic and analytical methods. Furthermore, the structures of 2a, 4, 5a, 5b and 6–9 have been elucidated by single‐crystal X‐ray crystallography. The X‐ray structures of 5a, 5b and 6–9 represent the first examples of crystallographically characterised nonsymmetric ditertiary phosphane complexes bearing one adamantane moiety. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Alternative synthetic route to chiral N‐substituted camphor‐derived β‐amino alcohols

An alternative route from (1R)-(+)-camphor to chiral N-substituted camphor-derived beta-amino alcohol (4b-e) consists of four steps with a total yield of 28%. N-Alkylation of camphor-derived beta-amino alcohol (4a) involves condensation and hydride reduction in one pot without isolation of intermediates. Condensation of 4a with aldehydes or ketones generates a mixture of 1,3-oxazolidines (6) and imino-alcohols (7), which are reduced to 4b-e by NaBH(4).

Stereoselective synthesis of a new chiral synthon: a cyclic pseudodipeptide containing an aspartic acid derivative and l-valine

A simple stereoselective synthesis of cyclic synthons 4a, b and 10a, b, derived from an l-valine unit and an unnatural derivative of the aspartic acid, has been accomplished starting from the chiral synthon 1 and following the procedure already reported by us for the synthesis of similar compounds. These cyclic synthons are interesting substrates because they can behave as both electrophiles and nucleophiles and could be useful starting materials for the preparation of higher peptides such as, for instance, the unnatural tetrapeptides 15 and 18, through the condensation of 4a with 6a or 13 with 17, respectively.

Stereochemistry of Disilanylene-Containing Cyclic Compounds. Synthesis and Reactions of cis- and trans-3,4-Benzo-1,2-di(tert-butyl)-1,2-dimethyl-1,2- disilacyclobut-3-ene

The reaction of cis- and trans-3,4-benzo-1,2-di(tert-butyl)-1,2-dimethyl-1,2-disilacyclobut-3-ene (1a and 1b) with chlorine gas in carbon tetrachloride proceeded stereospecifically to give meso- and rac-1,2-bis[(tert-butyl)chloromethylsilyl]benzene (2a and 2b, respectively). The condensation of 2a and 2b with lithium and sodium produced a mixture of cis- and trans-benzodisilacyclobutene 1a and 1b, respectively. The reaction of 1a and 1b with molecular oxygen proceeded with high stereospecificity to give the respective cis- and trans-4,5-benzo-2-oxa-1,3-disilacyclopent-4-ene. The palladium-catalyzed reactions of 1a and 1b with phenylacetylene, 1-hexyne, tert-butylacetylene, phenyl-1-propyne, and diphenylacetylene proceeded in a stereospecific fashion to give the corresponding 5,6-benzo-1,4-disilacyclohexa-2,5-diene derivatives. Similar reactions of 1a and 1b with trimethylsilylacetylene, dimethylphenylsilylacetylene, and mesitylacetylene gave stereospecifically the erythro- and threo-1,2-bis(silyl)benzene derivatives. The structure of trans-5,6-benzo-1,4-di(tert-butyl)-1,4-dimethyl-2-phenyl-1,4-disilacyclohexa-2,5-diene was determined by single-crystal X-ray crystallography.

Sugar‐Modified Conjugated Diene Analogues of Adenosine and Uridine: Synthesis, Interaction with S‐Adenosyl‐L‐homocysteine Hydrolase, and Antiviral and Cytostatic Effects.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Sugar-modified conjugated diene analogues of adenosine and uridine: synthesis, interaction with S-adenosyl-L-homocysteine hydrolase, and antiviral and cytostatic effects.

Moffatt oxidation of 2',3'-O-isopropylideneuridine (1a) and treatment of the crude 5'-aldehyde with formylmethylene-stabilized Wittig reagent gave the vinylogously extended 7'-aldehyde2a. Condensation of 2a with ethoxycarbonyl- or dibromomethylene phosphorane reagents gave the conjugated dienes 6a and 4a, respectively. Deacetonization gave diene ester 7a [5'(E),7'(E); with s-trans conformation] and dibromodiene 5a [5'(E)], respectively. Analogously, 2',3'-O-isopropylideneadenosine (1b) was Wittig-extended into the conjugated dibromodiene 5b [5'(E)] and dienoic ester 7b [5'(E),7'(E)]. Furthermore, palladium-catalyzed coupling of the vinyl 6'(E)-stannanes 14 with (E) and (Z) ethyl 3-iodoacrylate gave stereodefined access to dienoic esters 7 (E,E) and 16 (E,Z). Incubation of AdoHcy hydrolase with 100 microM of 5b resulted in partial inhibition of the enzyme without any apparent change in the enzyme's nicotinamide adenine dinucleoside (NAD(+)) content. In contrast, 7b and 16b produced time- and concentration-dependent inactivation of S-adenosyl-L-homocysteine (AdoHcy) hydrolase producing significant decreases in the enzyme's NAD(+) content. However, 7b and 16b upon incubation with AdoHcy hydrolase were not metabolized suggesting that these compounds are type I mechanism-based inhibitors. No specific antiviral activity was noted for 5a,b, 7a,b, and 16a,b against any of the viruses tested; dibromodiene 5b proved cytotoxic at a concentration > or =6.7 microM and cytostatic at > or =11 microM, while dienoic esters 16a,b showed activity against both varicella-zoster virus (at 10 microM, 16a) and cytomegalovirus (at 10 microM, 16a; 18 microM, 16b).

Synthesis and Protonation Behavior of 26-Membered Oxaaza and Polyaza Macrocycles Containing Two Heteroaromatic Units of 3,5-Disubstituted Pyrazole or 1-Benzylpyrazole. A Potentiometric and1H and13C NMR Study

The synthesis and acid−base behavior of two series of 26-membered dioxatetraamine and hexaamine heterocyclophanes containing two nuclei of either pyrazole (4a and 6a) or 1-benzylpyrazole (4b and 6b), respectively, are reported. Dipodal (2 + 2) condensations of 3,5-pyrazoledicarbaldehyde 2a or its 1-benzyl derivative 2b with 1,5-diamino-3-oxapentane afford in both cases the stable Schiff bases 3a,b in 90% yield, which after reduction with NaBH4 gave 4a,b in 75% and 84% yield, respectively. Condensation of 2a with diethylenetriamine leads to a complex mixture containing imidazolidine isomers, which was reduced in situ to afford 6a in 30% yield. Condensation of 2b with the same amine gave the stable diimidazolidine derivative 5b, which after crystallization was isolated as a pure compound in 80% yield and fully identified from analytical and 1H and 13C NMR data as a constitutional isomer with both imidazolidine rings located at the side of the pyrazole closer to the benzylic substituents. Reduction of 5b wit...

Total Synthesis of Two Prenylated Flavanonols From Maackia Tenuifolia

Abstract Two new prenylated flavanonols (1) and (2) isolated from the roots of Maackia tenuifolia were synthesized from resacetophenone (3). Prenylation of 3 with prenyl bromide in the presence of methanolic alkali gave 3-C-prenyl resacetophenone (4a), whereas in the presence of silver oxide catalyst, afforded mainly 5-C-prenyl resacetophenone (4b). Condensation of 4a and 4b with benzaldehyde yielded chalcones (5a and 5b) which were converted into racemic epoxides (7a and 7b) after methoxymethylation and epioxidation. Cyclization of epoxides (7a and 7b) resulted in formation of racemic flavanonols (8a and 8b).

Chemotherapeutic agents, XV. Synthesis of 4-amino-3-pyrazolo-1,2,4-triazoles as antimicrobial agents.

4-Amino-3-hydrazino-5-H/methyl-1,2,4-triazole dihydrochlorides (2a,b) were obtained by cyclization of triamino-guanidine-HCl in formic and acetic acids, respectively. Condensation of 2a with pyrazol-4-carbaldehydes in ethanol yielded 3a,b. Cyclocondensation of 2a,b with dimethylmercaptocyanoacrylonitrile, methyl dimethylmercapto-cyanoacrylate, ethoxymethylenemalononitrile and ethyl ethoxymethylenecyanoacetate individually provided 4a-d and 5a-d, respectively. The hydrazones 6a,b were obtained by refluxing 4-amino-3-(5-amino-4-ethoxycarbonyl pyrazol-1-yl)-1,2,4-triazole (5b) with aryl aldehydes in ethanol. Interaction of 2a with acetylacetone and 2-ethoxycarbonylcyclopentanone separately yielded 7 and 8 while reaction with 2-ethoxycarbonylcyclohexanone provided the bicyclic compounds 9a,b. Some of the compounds were screened for antibacterial and antifungal activities but none of them showed any significant activity.

Pyridazines with heteroatom substituents in position 3 and 5. 3. 2‐aryl‐5‐hydroxypyridazin‐3(2H)‐ones as potential herbicides: Synthesis and some reactions

AbstractThe coupling of dimethyl acetonedicarboxylate 1 with a variety of aryldiazonium salts 2a‐i produces the hydrazones 3a‐i which can be cyclized in boiling dichlorobenzene to yield the pyridazone esters 4a‐i, or in sodium hydroxide solution to give the pyridazone acids 5a‐f,h,i, which can be decarboxylated at elevated temperatures. The hydroxy group in 4a,d can be acylated, sulfonated or alkylated yielding compounds 8a‐n. Condensation of 4a,d with magic malonates 9a‐d produces the pyronopyridazinones 10a‐f. The reaction of 4a with hydrazine yields the hydrazide 12 via the salt 11, and with ammonia the amide 14.

β‐Carbolines derived from β‐methyltryptophan and a stereoselective synthesis of (2RS,3SR)‐β‐methyltryptophan methyl ester

AbstractThe methyl ester of isomer A of β‐methyltryptophan (2SR,3RS; 2A) was stereoselectively prepared by an efficient modified method through the reaction of a‐methyl‐N‐(1‐Methylethyl)‐1H‐indole‐3‐methanamine (3) with methyl nitroacetate to give the desired nitro compound as a mixture of two racemates 5A, and 5B. During the recrystallization process epimerization occurred and only racemate 5A crystallized out. Catalytic hydrogenation of 5A in the presence of acid stereoselectively yielded the desired amino acid ester 2A. Pictet‐Spengler condensation of 2A with aldehydes under aprotic conditions followed by dehydrogenation gave excellent yields of β‐carbolines 7a‐i, (R = methyl, ethyl, acetyl, phenyl, pyridine‐2‐yl, furan‐2‐yl, quinoline‐2‐yl, styryl, phenethyl). Also β‐carbolines 7a,b,i were synthesized by the Pictet‐Spengler condensation of (3‐meth‐yltryptophan under acidic aqueous conditions followed by esterification and dehydrogenation.

Synthesis of new substituted pyrazolo[1,5-a]-pyrimidines and pyrazolo[1,5-a]1,3,5-triazines

5-Substituted 3-amino-1H-pyrazole-4-carbonitriles 2a-d react with appropriate biselectrophilic reagents in the presence of (TEA) to give the substitution products pyrazolo[1,5-a]pyrimidines 4a-d, 6a-d and pyrazolo[1,5-a ]1,3,5-triazines 8a-d. Compounds 6a and 8a react with secondary amines to 10a-c and 11a-c. Treatment of 2a with malonodinitrile results in the substituted pyrazolo-[1,5-a]pyrimidine 16. Condensation of 2a, 2c and 2d with ethyli-dene-malodintriles leads to racemic dihydro-pyrazolo[1,5-a] pyr-imidines 18a-e. Reaction of diene 20 with the heterodienophile 21 leads to formation of Diels-Alder adduct 22.