Hydrazones 3a Research Articles

Synthesis, antimicrobial, analgesic activity, and molecular docking studies of novel 1-(5,7-dichloro-1,3-benzoxazol-2-yl)-3-phenyl-1H-pyrazole-4-carbaldehyde derivatives

Condensation of 5,7-dichloro-2-hydrazino-1,3-benzoxazole 3 with different aromatic acetophenones in methanol using catalytic amount of glacial acetic acid afforded the corresponding 1-phenylethanone(5,7-dichloro-1,3-benzoxazol-2-yl)hydrazones 5a–e in good yield. The compounds 5a–e, when subjected to Vilsmeier–Haack reaction with POCl3 in DMF yielded (5,7-dichloro-1,3-benzoxazol-2-yl)-3-phenyl-1H-pyrazole-4-carbaldehyde derivatives 6a–e. The structural assignments of the compounds 6a–e are based on their spectral data and elemental analysis. The obtained compounds were tested for antimicrobial and analgesic activities, and subjected to molecular docking studies with respect to antimicrobial activity. The compound 6b showed pronounced antimicrobial and analgesic activity and exhibited an interesting binding profile with very high receptor affinity.

Synthesis, characterization and antimicrobial evaluation of novel derivatives of isoniazid

In the present investigation, a series of new Mannich bases were prepared by the reaction of 2-ethoxybenzaldehyde with isoniazid to form acid hydrazone (3a). Further, C-Mannich bases of the above acid hydrazone were prepared by aminomethylation with formaldehyde and substituted secondary amines (3b–3k). The structures of newly synthesized compounds were evaluated by elemental analyses and spectral (IR, 1H NMR, 13C NMR) studies. All the synthesized compounds were evaluated for their antimicrobial activity. Amoxicillin was used as a standard drug for antibacterial activity while Nystatin was used as a standard drug for antifungal activity. Preliminary pharmacological evaluation revealed that the compound (3f, 3i, 3j, 3k) showed better performance against Bacillus subtilis,Staphylococcus aureus,Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Candida gabrata. The result demonstrates the potential and importance of developing new mannich bases which would be effective against resistant bacterial and fungal strain.

Ring-Closure Reactions of 1,2-Diaza-4,5-benzoheptatrienyl Metal Compounds: Experiment and Theory

2-Alkenylbenzylidene hydrazones 5a-m, which are accessible in good to excellent yields in a four-step synthesis, are converted into 1,2-diaza-4,5-benzoheptatrienyl metal compounds 1a-m by treatment with KO-t-Bu as base. These metal compounds undergo the various types of reactions in good yields and exclusively depending on the nature of substituents R(1) and R(3). Thus, metal compounds 1a-c carrying alkyl substituents R(1) and R(3) form 3H-benzodiazepines 6a-c after electrophilic quench of the intermediate cyclic anion 7 in a 7-endo-trig electrocyclic reaction with a möbius aromatic transition structure 1(-)-TS. Similarly, a benzothienyl derivative 5n is converted into diazepine 6d. Potassium compounds 1d-h, which are N-methyl and aryl substituted at R(3), form 1,2-dihydrophthalazines 8a-e in a predominantly charge-controlled 6-exo-trig cyclization reaction. In contrast, aryl-aryl-substituted systems 5i-m did not lead to cyclic products upon deprotonation, but the intermediate open-chain metal compounds 1i-m were trapped by acid chlorides at N1 to yield the hydrazides 10a-e. We interpret thermodynamics and kinetics of these reactions in the context of the Baldwin rules on the basis of quantum chemical calculations and discuss the transition structures considering the results of NICS and NBO-charge calculations. Examples of the products 6, 8, and 10 could be characterized by X-ray diffraction.

Synthesis of Biologically Active [4‐(4‐Bromophenyl)‐2‐thiazolyl]hydrazones and their D‐Galactose Derivatives

AbstractBenzaldehyde [4‐(4‐bromophenyl)thiazol‐2‐yl]hydrazones 5a–5d were prepared by reacting the thiosemicarbazones 2a–2d with 2,4′‐dibromoacetophenone (1) in absolute ethanol. Acetylation of 5a and 5b with Ac2O/Py at room temperature gave the N‐acetyl derivatives 6a and 6b. 4‐Methyl‐2‐pentanone/cyclopentanone [4‐(4‐bromo‐phenyl)thiazol‐2‐yl]hydrazones (8a) and (8b) were similarly obtained from the reaction of 1 with the thiosemicarbazones 7a and 7b, respectively. Cyclization of D‐galactose thiosemicarbazone (9) and its tautomers 10 and 11 with 1 afforded an equilibrium mixture of the acyclic 2‐thiazolylhydrazone 12, together with its respective cyclic galactosyl derivatives 13 and 14, whose structures were studied by using 1H and 13C NMR spectra. The antimicrobial activity of the synthesized thiazole derivatives was evaluated in vitro by using an agar diffusion technique, and some of these compounds showed potential activity against Candida albicans.

Preparation, Thermolysis, and Photolysis of Some New Thiophosphoramidates Derived from 3-Methyl-2-Benzothiazolinone Hydrazone

3-Methyl-2-benzothiazolinone hydrazone (1) reacts with dialkyl phosphorothiochloridates 2a,b in the presence of a base, to give the respective dialkylthiophosphorylated hydrazones 3a,b. Upon thermolysis, compound 3b yields bi(3-methylbenzothiazole-2-iminyl) (4). Exposure of 3b to sunlight in methanol results in the formation of 3-methyl-2-benzothiazolinone (5). When the same experiment was carried on the starting hydrazone 1, bis(3-methyl- benzothiazole-2-iminyl)diazine (6) was formed. Elemental analyses and spectroscopic details are presented for the new compounds. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Synthesis of some new Indeno[1,2-e]pyrazolo[5,1-c]-1,2,4-triazin-6-one and Indeno[2,1-c]pyridazine-4-carbonitrile Derivatives

Diazonium chlorides of 5-amino-3-methypyrazole 1a and 5-amino-4-phenylpyrazole 1b coupled with 1,3-indanedione 2 and led to the formation of acyclic hydrazone 3a and a cyclic product indenopyrazolotriazine 4b respectively. Cyclization of the hydrazone 3a by boiling in acetic acid afforded the corresponding 4a. The hydrazone 3a reacted with malononitrile in boiling ethanol in the presence of piperidine and gave indeno[2,1-c]pyridazine-4-carbonitrile derivatives 5a,b. Also, coupling of 6 with aryl diazonium chlorides gave the corresponding indenopyridazine derivatives 8a-e. Acetylation, benzoylation and hydrolysis of compound 8a afforded the corresponding substitution products 10-12, respectively. The structures of the newly synthesized compounds were established on the basis of chemical and spectral evidences.

A New One‐Step Synthesis of 1,2,4‐Triazino[2,3‐c]quinazolines.

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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.

A New One-Step Synthesis of 1,2,4-Triazino[2,3-c]quinazolines

A new and efficient one-step protocol for the synthesis of 3-substituted 2H-l,2,4-triazino[2,3-c]quinazolin-2-ones (5) was developed starting from 4-hydrazinoquinazoline (1) and α-ketocarboxylic acids and their esters. Corresponding hydrazones (2a,c and 3a,c,e) were isolated as intermediate products. Further cyclocondensation followed by acid-catalyzed Dimroth rearrangement resulted in the title derivatives 5.

Reactions of 5-Arylidene-2-thiohydantoins with Halogenated Compounds and Anthranilic Acid

5-arylidene-2-thiohydantoins 1a–c react with ethyl α -chloroacetate 2 and monochloroacetone to give the respective 2-imidazolinones 3a–c and 2-acetonylmercaptohydantoins 9a–c . Compounds 3a–c react with benzenediazonium chloride to afford hydrazones 5a–c . The reaction of 1a–c with ethylene bromide and with α,α -dichloroacetone gives the respective alkyl mercapto-derivatives 13a–c and 14a–c . The reaction of polyphosphoric acid with 3a–c , 9a–c , 13a–c and 14a–c yields the respective thiazolones 7a–c , imidazothioles 10a–c , imidazo-thiazoles 15a–c and imidazothiazines 16a–c . The mercapto-hydantoins 17a–d react with anthranilic acid to give quinazolin-3,5-diones 19a,b and/or 21a , b . Structural elucidation for the new products are based on compatible elementary and spectroscopic evidences.

Transformations of phenylhydrazones of dialkyl 2-oxo-propane-1,3-dicarboxylate and of ethyl acetoacetate in concentrated sulfuric acid

The hydrazones 3a,b, prepared from phenylhydrazine (1) and dialkyl 2-oxopropane-1,3-dicarboxylate (2a,b) were converted in concentrated sulfuric acid at −5 °C into a mixture of alkyl (3-carboxyindol-2-yl)acetates (5a,b), and ethyl (5-ethoxy-1-phenyl-1H-pyrazol-3-yl)acetate 6. The hydrazone 8, prepared from 1 and ethyl acetoacetate (7) was transformed under the same conditions into a mixture of five compounds: ethyl 2-methylindol-3-carboxylate (9), 2-methylindol-3-carboxylic acid (10), 2-methylindol (11), 5-ethoxy-3-methyl-1-phenyl-1H-pyrazole (12), and 3-methyl-1-phenyl-1H-pyrazol-5-one (13).

Formation of Novel Pyrido[3′,2′:4,5]Thieno [2,3-e][1,2,4]Triazolo[4,3-c] Pyrimidines and their Acyclic C-Nucleosides Analogues: Synthesis of 3-(Alditol-1-yl)Pyridothienotriazolopyrimidines

A series of the hydrazones were prepared by the reaction of 4-hydrazino-7,9-dimethylpyrido[3′,2′:4,5]thieno [2,3-d]pyrimidine (1) with monosaccharides, and their acetylation was studied. The oxidative cyclisation of the hydrazones 3a–c gave 3-(Alditol-1-yl)-pyridothienotriazolopyrimidenes 5a–c, whose acetylation was carried out. Also, oxidative cyclisation of arylidenes 7a,b gave the pyridothienotriazolopyrimidines 8a,b.

The Isoindazole Nucleus as a Donor in Fullerene‐Based Dyads. Evidence for Electron Transfer.

A series of isoindazole-C60 dyads 4a−c based on pyrazolino[60]fullerene have been prepared by 1,3-dipolar cycloadditions of the nitrile imines, generated in situ from hydrazones 3a−c, to C60. Molecular orbital calculations for 4b revealed that the electron distribution of the HOMO is located on the isoindazole moiety, while the electron distribution of the LUMO is located on the C60 moiety. Electrochemical properties of the new dyads 4a−c show a similar electron affinity with respect to C60. Charge-transfer interactions in the ground state between the isoindazole ring and the fullerene cage are predicted by the molecular orbital calculations and confirmed by electrochemical studies in 4a,b. Steady-state fluorescence emission spectra of dyads 4a−c show that fluorescence intensities in polar benzonitrile solvent decrease with increasing electron-donating ability of the substituent attached on the isoindazole group. This was confirmed by the shortening of fluorescence lifetimes, from which intramolecular cha...

Synthesis and Biological Activities of Novel 2‐(5′‐Substituted‐3′‐phenylindole‐2′‐yl)‐1,3,4‐oxadiazino[5,6‐b]indole and 3‐(5′‐Substituted‐3′‐phenylindole‐2′‐amido)spiro‐ (indol‐3′′,2‐thiazolidine)‐2′′,4‐diones.

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The isoindazole nucleus as a donor in fullerene-based dyads. Evidence for electron transfer.

A series of isoindazole-C(60) dyads 4a-c based on pyrazolino[60]fullerene have been prepared by 1,3-dipolar cycloadditions of the nitrile imines, generated in situ from hydrazones 3a-c, to C(60). Molecular orbital calculations for 4b revealed that the electron distribution of the HOMO is located on the isoindazole moiety, while the electron distribution of the LUMO is located on the C(60) moiety. Electrochemical properties of the new dyads 4a-c show a similar electron affinity with respect to C(60). Charge-transfer interactions in the ground state between the isoindazole ring and the fullerene cage are predicted by the molecular orbital calculations and confirmed by electrochemical studies in 4a,b. Steady-state fluorescence emission spectra of dyads 4a-c show that fluorescence intensities in polar benzonitrile solvent decrease with increasing electron-donating ability of the substituent attached on the isoindazole group. This was confirmed by the shortening of fluorescence lifetimes, from which intramolecular charge-separation rates and efficiencies via the excited singlet states of the fullerene moiety were evaluated. The yields of the triplet states in polar solvent decrease with the electron-donating ability, supporting the competitive formation of the charge-separated state with the intersystem crossing from the excited states. Thus, isoindazole[60]fullerene 4b can be considered a molecular switch with an AND logic gate.

Synthesis and antitubercular activity of 4-(3-coumarinyl)-3-cyclohexyl-4-thiazolin-2-one benzylidenehydrazones

In this study, a new series of 4-(3-coumarinyl)-3-cyclohexyl-4-thiazoline-2-one benzylidene hydrazones ( 3a– p) were synthesized. Structures of the title compounds were determined by analytical and spectral methods. 3a– p were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv.

Crystallographic, NMR and ab initio calculation studies of tautomerism among substituted dihydrothiazol-2-ylhydrazones

The structures of (±)-dihydrothiazolyl hydrazones 3a,b have been fully characterized by combining crystallography, NMR measurements in solution, and computational methods. The thiazolidine structure of the heterocycle is confirmed both by crystallography and in solution. The stability of the endocyclic N3 tautomeric form is confirmed by energy calculation at the MP2/6-31+G(d) level. The anti-E conformation observed in the crystal structures is retained in solution, in agreement with stability prediction.

Palladium-catalyzed allylic alkylation using chiral hydrazones as ligands.

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (4) with a dimethyl malonate-BSA-LiOAc system and its derivatives has been successfully carried out in the presence of a new chiral hydrazone ligands such as 2-(diphenylphosphino)benzaldehyde SAMP hydrazone (DPPBA-SAMP) (3a) in high yields with high enantioselectives.

Asymmetric β-Aminoethylation of Ketones and Nitriles with Tosylaziridines Employing the SAMP-Hydrazone Method

The nucleophilic ring-opening of tosylaziridines with chiral aza-enolates is reported. The SAMP-/ RAMP-hydrazones 1a−h derived from aldehydes or ketones were reacted with tosylaziridine 2a to give the β-aminoethylated hydrazones 3a−h with good diastereoselectivity. Removal of the chiral auxiliary resulted in the formation of the γ-amino nitriles 4a−e or γ-amino ketones 6f−h in good yields and excellent enantiomeric excesses (ee ⩾ 98%). Ring-opening of the enantiopure, benzyl-substituted tosylaziridine 2b with aza-enolates was achieved selectively at the less-substituted ring-carbon atom, again with excellent diastereoselectivity. Subsequent cleavage of the chiral auxiliary yielded the γ-benzyl-substituted γ-amino nitrile 4j or γ-amino ketone 6i with de,ee ⩾ 98%, respectively. The relative and absolute configuration of the new stereogenic centre of the aminoethylated hydrazones 3a−j was determined by NOE measurements and confirmed by X-ray structure analysis on the Mosher amide of 6h.

Synthesis and antimycobacterial activity of some coupling products from 4-aminobenzoic acid hydrazones

Various 2,3,4-pentanetrione-3-[4-[[(5-nitro-2-furyl/pyridyl/substituted phenyl)methylene]hydrazinocarbonyl]phenyl]hydrazones 3a–j were synthesized by the reactions of acetylacetone with the diazonium salts of 4-aminobenzoic acid-[(5-nitro-2-furyl/pyridyl/substituted phenyl)methylene]hydrazides 2a–j at 0–5 °C. The structures of these compounds were determined using spectral data. All the synthesized compounds were evaluated for their antimycobacterial activity against Mycobacterium fortuitum ATCC 6841 and Mycobacterium tuberculosis H37Rv. Of the compounds screened, 2e, 2i, 3e and 3g were found to be active against M. fortuitum at an MIC value of 32 μg/mL. Compound 3a, which exhibited > 90% inhibition in the primary screen at 12.5 μg/mL against M. tuberculosis H37Rv, was the most promising derivative for antituberculosis activity. Results obtained from the level II screening showed that the actual MIC and IC 50 values of 3a were 3.13 and 0.32 μg/mL, respectively. The same compound was also tested against Mycobacterium avium, which was observed not to be susceptible to 3a.