Aryl Hydrazines Research Articles

Microwave-assisted synthesis of pyrano[2,3-c]-pyrazole derivatives and their anti-microbial, anti-malarial, anti-tubercular, and anti-cancer activities

We have described solvent-free preparation of new pyrano[2,3-c]-pyrazole-5-carbonitriles (1-10) from the reaction of 1,3-diketo ester, aryl hydrazine, aromatic aldehyde, and malononitrile catalyzed by Zinc triflate (which was recycled and reused up to five times) under microwave irradiation (MWI) at 80–120 °C. An augmented yield with shorter reaction times is the added advantage of the present work. All synthesized molecules were screened for anti-malarial, anti-microbial, anti-tuberculosis, and anti-cancer activities. Most of the tested compounds exhibited prominent anti-bacterial and anti-malarial activity, and some analogs showed anti-cancer activity.

Synthesis and X-ray Crystal Structure of New Substituted 3-4′-Bipyrazole Derivatives. Hirshfeld Analysis, DFT and NBO Studies

A new compounds named 3-4′-bipyrazoles 2 and 3 were synthesized in high chemical yield from a reaction of pyran-2,4-diketone 1 with aryl hydrazines under thermal conditions in MeOH. Compound 2 was unambiguously confirmed by single-crystal X-ray analysis. It crystalizes in a triclinic crystal system and space group P-1. Its crystal structure was found to be in good agreement with the spectral characterizations. With the aid of Hirshfeld calculations, the H…H (54.8–55.3%) and H…C (28.3–29.2%) intermolecular contacts are the most dominant, while the O…H (5.8–6.5%), N…H (3.8–4.6%) and C…C (3.0–4.9%) are less dominant. The compound has a polar nature with a net dipole moment of 6.388 Debye. The BD(2)C31-C32→BD*(2)N4-C34 (27.10 kcal/mol), LP(1)N5→BD*(2)C31-C32 (36.90 kcal/mol), BD(1)C32-C34→BD*(1)C18-C31 (6.78 kcal/mol) and LP(1)N4→BD*(1)N5-C31 (7.25 kcal/mol) are the strongest π→π*, n→π*, σ-σ* and n→σ* intramolecular charge transfer processes, respectively.

Palladium-Catalyzed Domino Aminocarbonylation of Alkynols: Direct and Selective Synthesis of Itaconimides.

The first direct and selective synthesis of substituted itaconimdes by palladium-catalyzed aminocarbonylation of alkynols is reported. Key to the success of this transformation is the use of a novel catalyst system involving ligand L11 and appropriate reaction conditions. In the protocol here presented, easily available propargylic alcohols react with N-nucleophiles including aryl- and alkylamines as well as aryl hydrazines to provide a broad variety of interesting heterocycles with high catalyst activity and excellent selectivity. The synthetic utility of the protocol is demonstrated in the synthesis of natural product 11 with aminocarbonylation as the key step. Mechanistic studies and control experiments reveal the crucial role of the hydroxyl group in the substrate for the control of selectivity.

STUDY ON SYNTHESIS AND STRUCTURE OF SOME HYDRAZONES FROM 3,4-DIMETHOXY-2-NITROBENZALDEHYDE

Three new hydrazones were synthesized by condensation reaction between 3,4-dimethoxy-2-nitrobenzaldehyde and aryl hydrazine hydrochlorides. 3,4-Dimethoxy-2-nitrobenzaldehyde needed for the Schiff base-imine condensation reaction was synthesized from vanillin through esterification, nitration, hydrolysis, and methylation reactions. All products were purified by re-crystallization in a suitable solvent. The structures of three new hydrazones were determined by 1H NMR, 13C NMR, and MS.

Effect of Terminal Alkylation of Aryl and Heteroaryl Hydrazines in the Fischer Indole Synthesis

The effect of alkylation on the terminal position of aryl and heteroaryl hydrazines in the Fischer indole synthesis was examined. Compared to their unalkylated counterparts, reactions using alkylated hydrazines provided indole products with higher yields and faster rates. The reactions can be conducted at lower temperatures and are compatible with acid-sensitive functionality. The terminally alkylated hydrazines were readily prepared by a new two-step sequence and held as stable hydrazinium salts. The mild formation of the salts along with the favorable Fischer indole reaction conditions highlights the potential of this approach in later-stage synthetic use.

Continuous-Flow Nickel/Photocatalytic C–N Cross-Coupling of Aryl Halides and Hydrazine Nucleophiles

Key words nickel catalysis - iridium catalysis - photocatalysis - C–N coupling - hydrazine

One-pot, three-component Fischer indolisation-N-alkylation for rapid synthesis of 1,2,3-trisubstituted indoles.

A one-pot, three-component protocol for the synthesis of 1,2,3-trisubstituted indoles has been developed, based upon a Fischer indolisation-indole N-alkylation sequence. This procedure is very rapid (total reaction time under 30 minutes), operationally straightforward, generally high yielding and draws upon readily available building blocks (aryl hydrazines, ketones, alkyl halides) to generate densely substituted indole products. We have demonstrated the utility of this process in the synthesis of 23 indoles, benzoindoles and tetrahydrocarbazoles bearing varied and useful functionality.

An efficient (TBA)2S2O8 catalyzed regioselective solvent-free one-pot synthesis of fully substituted pyrazoles

An efficient tetra-n-butyl ammonium peroxydisulphate (TBA)2S2O8 catalyzed a direct one-pot synthesis of fully substituted pyrazoles in excellent yields with high regioselectivity has been described via a three-component cyclocondensation of aldehydes, aryl hydrazines with β-diketones or β-keto esters under solvent-free conditions. The structure of the target compound 4 m was confirmed by X-ray diffraction.

Palladium-Catalyzed Cross-Coupling of Aryl Halides and Hydrazine

Key words palladium catalysis - cross-coupling - hydrazine - aryl halides - amination

Organocatalytic Hantzsch Type Reaction Using Aryl Hydrazines, Propiolic Acid Esters and Enals: Enantioselective Synthesis of Paroxetine

AbstractAryl hydrazines, propiolic acid esters and enals serve as a viable substrate combination for an organocatalytic enantioselective Hantzsch type reaction. The method converts readily available starting materials into important chiral heterocycles with good to excellent yields and enantioselectivities, and has addressed the longstanding scope limitation of the classic Hantzsch reaction in the asymmetric synthesis of 2,6‐unsubstituted hydropyridines. The synthetic utility has been demonstrated by the concise enantioselective synthesis of paroxetine.magnified image

Cross-Coupling between Hydrazine and Aryl Halides with Hydroxide Base at Low Loadings of Palladium by Rate-Determining Deprotonation of Bound Hydrazine.

Reported here is the Pd-catalyzed C-N coupling of hydrazine with (hetero)aryl chlorides and bromides to form aryl hydrazines with catalyst loadings as low as 100 ppm of Pd and KOH as base. Mechanistic studies revealed two catalyst resting states: an arylpalladium(II) hydroxide and arylpalladium(II) chloride. These compounds are present in two interconnected catalytic cycles and react with hydrazine and base or hydrazine alone to give the product. The selectivity of the hydroxide complex with hydrazine to form aryl over diaryl hydrazine was lower than that of the chloride complex, as well as the catalytic reaction. In contrast, the selectivity of the chloride complex closely matched that of the catalytic reaction, indicating that the aryl hydrazine is derived from this complex. Kinetic studies showed that the coupling process occurs by rate-limiting deprotonation of a hydrazine-bound arylpalladium(II) chloride complex to give an arylpalladium(II) hydrazido complex.

Cross‐Coupling between Hydrazine and Aryl Halides with Hydroxide Base at Low Loadings of Palladium by Rate‐Determining Deprotonation of Bound Hydrazine

AbstractReported here is the Pd‐catalyzed C–N coupling of hydrazine with (hetero)aryl chlorides and bromides to form aryl hydrazines with catalyst loadings as low as 100 ppm of Pd and KOH as base. Mechanistic studies revealed two catalyst resting states: an arylpalladium(II) hydroxide and arylpalladium(II) chloride. These compounds are present in two interconnected catalytic cycles and react with hydrazine and base or hydrazine alone to give the product. The selectivity of the hydroxide complex with hydrazine to form aryl over diaryl hydrazine was lower than that of the chloride complex, as well as the catalytic reaction. In contrast, the selectivity of the chloride complex closely matched that of the catalytic reaction, indicating that the aryl hydrazine is derived from this complex. Kinetic studies showed that the coupling process occurs by rate‐limiting deprotonation of a hydrazine‐bound arylpalladium(II) chloride complex to give an arylpalladium(II) hydrazido complex.

New Insights into Catechol Oxidation – Application of Ammonium Peroxydisulfate in the Presence of Arylhydrazines

AbstractThe oxidative polymerisation of catechols in the presence of amino groups is an important reaction leading to polymers or oligomers of great practical importance. We present here, the oxidative polymerisation in the presence of nitro‐substituted aryl hydrazines using ammonium peroxydisulfate (APS) as oxidizing reagent in the presence of Tris‐buffer. Mixtures of deeply coloured oligomers are formed and analysed by FTIR‐, NMR‐, ESR‐spectroscopy and, in particular, by HR‐ESI MS. The reaction occurred by C−C, C−O and C−N bond formation leading to aryl‐aryl, aryl‐O‐aryl, aryl‐N=N structural elements. In some cases, both N‐atoms of the starting aryl hydrazine have been lost during reaction. Remarkably, diaryl azo compounds as structurally similar with azo dyes were also formed. Their reaction with APS was investigated. These results provide new insight into the oxidative depletion of azo dyes with APS in industrial waste water treatment.

RЕACTION OF O-ARYL(METHYL)SULFONATES OF 1,4-QUINONE MONOOXIMES WITH HYDRAZINES

Aroylhydrazones contain the active pharmacophore group >C=N–NH–CO–. These compounds show antimicrobial, antibacterial, and even anticancer activity. In addition, aroylhydrazones are synthons in the synthesis of various heterocyclic compounds. The purpose of this work is to define the features of the reaction of aryl(benzoyl)hydrazines with O-sulfonates of 1,4-quinone monooxime and to synthesize the benzoquinone hydrazones based on them. In the result of reaction of 1,4-quinone monoxime O-sulfonates with phenylhydrazine the p-tolyl(methyl)sulfates of the corresponding aminophenols were obtained. Subsequent treatment of these sulfates with water and acidification led to sulfate destruction and formation of a mixture of the corresponding aminophenol and p-tolyl(methyl)sulfate acid. We did not obtain 1,4-benzoquinone hydrazones. Thus, in the reaction of 1,4-quinone monoxime O-sulfonates with phenylhydrazine, the first stage is the N–O bond break with reduction of quinoid ring, and this redox process is due to the high basicity of aryl hydrazines. The aroylhydrazones of 1,4-benzoquinone were obtained only in the reaction of aroylhydrazines with 1,4-quinone monoxime O-sulfonates, containing two alkyl substituents in the both orthopositions to the carbonyl group of the quinoid ring. The first step of this reaction is also the =N–O– bond breaking of the starting sulfonates and formation of corresponding quinone imines. 2,6-Disubstituted quinone monoimines have less redox potential, and aroylhydrazines are less basic than arylhydrazines, therefore, the formation of corresponding aroylhydrazones of 1,4-benzoquinone is possible. The variation of the substituent attached to the oxygen atom of the starting 1,4-quinone monooxime O-sulfonates (MeSO2 or Ts) does not affect the reaction route.

Generation of Aryl Radicals from Aryl Hydrazines via Catalytic Iodine in Air: Arylation of Substituted 1,4-Naphthoquinones.

Arylated building blocks or heterocycles are key to myriad applications, including pharmaceutical drug discovery, materials sciences, and many more. Herein, we have reported a mild and efficient strategy for generation of aryl radicals by reacting appropriate aryl hydrazines with catalytic iodine in open air. The aryl radicals were quenched by diversely substituted 1,4-napthoquinones present in the reaction mixture to afford diversely substituted 2,3-napthoquinones in moderate to excellent yield. Control experiments provided insights into the putative reaction mechanism.

Iodine-Catalyzed Aerobic Diazenylation-Amination of Indole Derivatives.

A mild strategy for consecutive diazenylation and amination of indole moieties has been demonstrated. The functionalization occurs at C3 and C2 carbon atoms, respectively, at the indole scaffold in the presence of catalytic iodine and air at 40 °C in the 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) solvent. It is noteworthy that the aromatic amines are generated in situ by the reaction of aryl hydrazine with iodine. In general, bright red products are obtained in moderate to good yield. Control reactions are conducted to establish the reaction mechanism.

α-Diazoacetamides in Sc(OTf)3-Catalyzed Tiffeneau–Demjanov Ring Expansion: Application towards the Synthesis of Rare Bicyclic Pyrazoles

A novel Sc(OTf)3-catalyzed Tiffeneau–Demjanov ring expansion of six-membered cyclic ketones has been developed. The resulting seven-membered cyclic β-keto carboxamides were found to be versatile precursors to rare bicyclic pyrazoles obtained in modest to good yields via condensation with aryl hydrazines in the presence of Lawesson’s reagent.

The base-induced regioselective radical arylation of 3-aminochromone with aryl hydrazine.

A simple and efficient direct radical C-2 arylation of 3-aminochromone derivatives with aryl hydrazine is described. The aryl hydrazine acts as an initiator and source for the aryl radical via the cleavage of the C-N bond of aryl hydrazine. The reaction proceeds via a base-promoted single electron transfer (SET) pathway. The aryl radical abstracts a single electron from 3-aminochromone, which generates a C2-radical iminium ion to undergo a cross-coupling reaction with an aryl radical, and this process offers an array of regioselective 2-aryl substituted 3-aminochromones.

One-pot synthesis of imidazo[1,2-α]pyridine thioethers using imidazo[1,2-α]pyridines, arylsulfonyl chlorides and hydrazine

A one-pot reaction of making RS-substituted imidazo[1,2-α]pyridine derivatives by directly using aryl or alkylsulfonyl chloride and hydrazine was developed, selectively giving good yields of the expected products. Compared with previously reported methods of using ArSO2NHNH2 as a sulfur source, this method is much cheaper, more practical and convenient and enriches current methods to make thioether-containing compounds, providing a good example of green chemistry.

SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF SOME NOVEL 3,4-DISUBSTITUTED PYRAZOLE DERIVATIVES

Objective: The objective of the current work was to synthesize a series of 3,4-substituted pyrazoles from the cyclization of substituted aryl ethanone and hydrazine hydrate in a two-step process and screen the derivatives for their antimicrobial activity.
 Methods: The title compounds were derived from the condensation of ethanone intermediate with N, N-Dimethyl formamide-dimethyl acetal and hydrazine hydrate. Ethanone intermediate synthesized from substituted methyl phenylacetate in the presence of potassium t-butoxide with 6-methyl pyridine-2-carboxylic acid methyl ester.
 Results: The final products were characterized by detailed spectral analysis using Mass, Nuclear Magnetic Resonance, and Infra Red spectroscopy. All the compounds (4a-4j) showed significant antibacterial properties on both Gram-positive and Gram-negative bacteria. Interestingly, the selected microbes were found to be highly sensitive for compound 4a, 4c, 4d, 4h, and 4i. The molecules are also antifungal in nature, and they have a significant inhibitory effect on the growth of Candida albicans and Aspergillus niger.
 Conclusion: The results suggest that the developed derivatives bearing the pyrazole nucleus could be the lead structures for the development of antimicrobial agents for fatal infections.