Heteroaromatic Aldehydes Research Articles

Synthesis and antimycobacterial evaluation of pyridinyl- and pyrazinylhydrazone derivatives

Bioisosteric replacements are often tried goaling to affect the lipophilicity, polarity, and aqueous solubility of the substances, as a way to obtain therapeutically improved medicines. Also, hydrazonyl compounds are described with a wide range of pharmacological activities, having also recognized activities in antimycobacterial field. In this study, twenty-seven pyrimidinyl and pyrazinyl derivatives have been synthesized and evaluated for their antimycobacterial activity against M. tuberculosis ATTC 27294. The componds were obtained by the reaction of 2-hydrazinylpyridine, 4-hydrazinylpyridine, or 2-hydrazinylpyrazine with appropriated aromatic or heteroaromatic aldehydes. Antimycobacterial activity of the compounds was determined according to MTT assay. The most active compound, a 2-hydroxyl-5-nitrophenyl-4-pyridinylhydrazone derivative, showed good biodisponibility and nonmutagenic or tumorigenic profiles in preliminaries in silico studies, and exceptional in vitro activity, being compared with the reference drug ethambutol. This study supports that pyrimidinyl and pyrazinyl derivatives may be used for the development of new tuberculostatic agents.

Decarboxylative Formylation of Aryl Halides with Glyoxylic Acid by Palladium Catalysis under Oxygen

A new free radical/palladium cooperative catalyzed formylation of aryl halides with glyoxylic acid as the formyl source under oxygen conditions has been developed. Various aromatic and heteroaromatic aldehydes were produced in medium to good yields.

Antinociceptive and Antimicrobial Activity of Products from Reactions of Pyrrolobenzoxazinetriones with Thiosemicarbazones of Aromatic and Heteroaromatic Aldehydes

Previously, a series of hetareno[e]pyrrole-2,3-diones was found to include compounds with high antimicrobial and antinociceptive activity and low toxicity, so that new hetareno[e]pyrrole-2,3-dione derivatives were expected to have these types of activity. The reactions of pyrrolobenzoxazinetriones with a series of aromatic aldehyde thiosemicarbazones and nicotinic aldehyde thiosemicarbazone are reported. Results from studies of the antinociceptive (hot-plate test) and antimicrobial activity (Staphylococcus aureus No. 906, Escherichia coli No. 1257) are given. The most active compounds were effective on the level of the reference drugs. The target of the antinociceptive activity of the tested compounds was considered nerve endings because signs of central action were not observed in the behavior of animals under the influence of the compounds. The selective antimicrobial activity against Gram-positive bacteria S. aureus was presumably associated with disruption of the cytoplasmic membrane permeability and bacterial RNA synthesis.

Selective PdII‐Catalyzed Acylation of Pyrrole with Aldehydes. Application to the Synthesis of Celastramycin Analogues and Tolmetin

The PdII‐catalyzed C‐2 acylation of pyrrole with aldehydes in the presence of TBHP as oxidant has been studied for the synthesis of di(hetero)aryl ketones. The use of 2‐pyrimidine as directing group leads to 2‐acylpyrroles in moderate to good yields, although 2,5‐diacylpyrroles are obtained as by products. This side‐reaction could be avoided using 3‐methy‐2‐pyridine as directing group, obtaining selectively 2‐acylpyrroles. The reaction has been extended to a series of aromatic and heteroaromatic aldehydes, obtaining the best results with electron rich aromatic aldehydes. The methodology has been applied in the synthesis of pyrrolomycin alkaloid Celastramycin analogues and for an improved synthesis of Tolmetin, a nonsteroidal anti‐inflammatory drug.

1, 1’-Sulfinyldiethylammonium Bis (Hydrogen Sulfate) as a Recyclable Dicationic Ionic Liquid Catalyst for the Efficient Solvent-free Synthesis of 3, 4-Dihydropyrimidin-2(1H)-ones via Biginelli Reaction

A facile and efficient method for synthesis of 3, 4-dihydropyrimidin-2(1H)-ones via Biginelli reaction catalyzed by a novel dicationic Brönsted acidic ionic liquid, [(EtNH2)2SO][HSO4]2, has been successfully developed. 3, 4-Dihydropyrimidin-2(1H)-ones were synthesized through one-pot condensation of aromatic aldehydes, ethyl acetoacetate, and urea under solvent-free conditions using [(EtNH2)2SO][HSO4]2 as a novel catalyst. The progress of the reaction was monitored by thin-layer chromatography (ethyl acetate / n-hexane = 1 / 5). The products have been characterized by IR, 1H NMR, 13C NMR, and also by their melting points. In this research, a library of dihydropyrimidinone derivatives was synthesized via Biginelli reaction under solvent-free conditions at 120oC using [(EtNH2)2SO][HSO4]2 as a catalyst. Various aromatic aldehydes, as well as heteroaromatic aldehydes, were employed, affording good to high yields of the corresponding products and illustrating the substrate generality of the present method. In addition, the prepared dicationic Brönsted acidic ionic liquid can be easily recovered and reused. 1, 1'-Sulfinyldiethylammonium bis (hydrogen sulfate), as a novel dicationic ionic liquid, can act as a highly efficient catalyst for the synthesis of 3, 4-dihydropyrimidin-2(1H)-ones under solvent-free conditions.

α-Chymotrypsin-Induced Acetalization of Aldehydes and Ketones with Alcohols

This is the first report of a simple and general method for acetalization­ of aldehydes via an α-chymotrypsin-induced reaction under mild conditions. A broad range of aromatic and heteroaromatic aldehydes have been acetalized under neutral conditions in good yields using a catalytic amount of chymotrypsin.

Non‐Enzymatic Hybrid Catalysis for Stereoconversion of l‐Amino Acid Derivatives to d‐Isomers

AbstractA catalytic transformation of N‐unprotected l‐amino esters to N‐protected d‐amino esters was developed. The combined use of a heteroaromatic aldehyde, Lewis acid, palladium complex, and chiral Brønsted acid was a key factor for the successful operation of this catalytic system. The synergistic cooperation of an appropriate aldehyde and Lewis acid was crucial for promoting an efficient racemization of l‐amino esters, while the combination of a palladium complex and chiral phosphoric acid enabled dynamic kinetic resolution through asymmetric N‐allylation, providing N‐protected d‐amino esters in good yields with up to 97 : 3 er. Following appropriate deprotection processes, d‐amino acids were obtained without loss of enantiomeric purity.

A one-pot three-step multicomponent synthesis of functionalized allyl dithiocarbamates using Baylis–Hillman reaction

A one-pot, pseudo five-component, highly diastereoselective, and mild procedure for the synthesis of functionalized allyl dithiocarbamates is developed. The Baylis–Hillman (BH) reaction of aromatic (heteroaromatic) aldehydes and activated alkenes using DABCO, followed by acetylation of BH adducts with acetic anhydride in the presence of a catalytic amount of DMAP, and nucleophilic substitution reaction by in situ prepared dithiocarbamates from amines and CS2 are three steps of this protocol.

A Facile, Efficient and Solvent-Free Titanium (IV) Ethoxide Catalysed Knoevenagel Condensation of Aldehydes and Active Methylenes

: Titanium ethoxide has been employed as a novel and efficient reagent for the Knoevenagel condensation of aldehydes with active methylenes such as diethyl malonate and ethyl cyanoacetate under solvent free conditions to afford substituted olefins in high to excellent yields. The reaction is suitable for a variety of aromatic, aliphatic and heteroaromatic aldehydes with various active methylenes. Parallel to this, microwave irradiation has been utilized to achieve improved reaction rates and enhanced yields. Herein, we illustrated a convenient method for the preparation of α,β-unsaturated compounds using both conventional and microwave irradiation methods. An efficient and solvent free Knoevenagel condensation between aldehydes and active methylenes was developed using titanium ethoxide. The procedure proved to be successful with a wide range of substrates such as aromatic, aliphatic and heterocyclic aldehydes and various active methylenes to afford substituted olefins. The reaction was also carried out under microwave irradiation to accomplish the corresponding olefins with improved reaction rates, yields and cleaner reaction profiles.We have developed an efficient and novel methodology for the synthesis of olefinic compounds by Knoevenagel condensation under solvent-free conditions using titanium ethoxide, for the first time, as a reagent as well as a solvent. This method is appropriate for the synthesis of a variety of aromatic aldehydes containing various electron-donating and withdrawing groups, aliphatic and heteroaromatic aldehydes. The significant advantages offered by this methodology could be applied to various active methylenes in order to offer the corresponding Knoevenagel products. Thus, we believe that this method delivers high conversions, cleaner reaction profiles under solvent-free reaction conditions and shorter reaction times, all of which make it a very useful and attractive approach for the preparation of a wide range of substituted olefins.

A Brief Synthesis of 2,2'-Arylmethylene Bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1- one) Catalyzed by TEAOH in Various Solvents.

2,2'-Arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) having four carbonyl functionalities along with their tautomeric keto-enol forms, is an important biologically active compound and important synthetic intermediate in the synthesis of xanthenes. This study was conducted in order to develop a new and concise method of synthesis of 2,2'-arylmethylene bis (3-hydroxy-5,5-dimethyl-2- cyclohexene-1-one) derivatives. TEAOH (20 mol %) was fond to be as a simple and efficient catalyst for the preparation of 2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) derivatives by the Knoevenagel condensation/Michael addition tandem reactions. A concise and practical method was developed for one-pot synthesis of 2,2'-arylmethylene bis(3- hydroxy-5,5-dimethyl-2-cyclohexene-1-one) derivatives catalyzed by TEAOH at room temperature in various solvents. This strategy provides several advantages over the traditional synthetic method, and is applicable to a wide variety of aromatic and heteroaromatic aldehydes at room temperature in various solvents.

Construction of Chiral 2,3-Allenols through a Copper(I)-Catalyzed Asymmetric Direct Alkynylogous Aldol Reaction.

Chiral 2,3-allenols were constructed through copper(I)-catalyzed asymmetric direct alkynylogous aldol reaction. With aromatic and heteroaromatic aldehydes, the alkynylogous aldol reaction with (R)-DTBM-SEGPHOS as the ligand proceeded smoothly to furnish the products in excellent regioselectivity with good to high diastereoselectivity and excellent enantioselectivity. In the cases of aliphatic aldehydes, esters of but-2-yn-1-ol as the substrates and (R,R)-Ph-BPE as the ligand were found to be crucial to get good to high regio- and diastereoselectivity. The produced chiral 2,3-allenols are easily transformed into synthetically useful 2-furanones through cyclization. Finally, the developed method was successfully applied in the rapid synthesis of two chiral intermediates toward the synthesis of two pharmaceutically active compounds that have been proposed for the treatment of neurological disorders.

Herbicidal Activity of Flavokawains and Related trans-Chalcones against Amaranthus tricolor L. and Echinochloa crus-galli (L.) Beauv.

Flavokawains have a broad spectrum of biological activities; however, the herbicidal activity of these naturally occurring chalcones has been less investigated. Flavokawains and their analogues were prepared by the Claisen–Schmidt condensation reaction between xanthoxyline (or aromatic ketones) and a variety of aromatic and heteroaromatic aldehydes. These compounds were then evaluated for their inhibitory effect against representative dicot and monocot plants. Among 45 synthetic chalcones, derivatives containing phenoxyacetic acid, 4-(N,N-dimethylamino)phenyl, N-methylpyrrole, or thiophenyl groups inhibited the germination and growth of Chinese amaranth (Amaranthus tricolor L.) with moderate to high degrees compared to commercial butachlor. For barnyardgrass (Echinochloa crus-galli (L.) Beauv.), most of the thiophenyl chalcones interrupted shoot and root emergence. This finding highlighted the importance of functional groups on the herbicidal activity of chalcones. The level of inhibition also depended on the applied concentrations, plant species, and plant organs. (E)-2-(2-(3-Oxo-3-(thiophen-2-yl)prop-1-enyl)phenoxy)acetic acid (14f) was the most active compound among 45 derivatives. This chalcone could be a promising structure for controlling the germination and growth of weeds. The structure–activity relationship results provide useful information about the development of active chalconoids as novel natural product-like herbicides.

Construction of Chiral 2,3‐Allenols through a Copper(I)‐Catalyzed Asymmetric Direct Alkynylogous Aldol Reaction

AbstractChiral 2,3‐allenols were constructed through copper(I)‐catalyzed asymmetric direct alkynylogous aldol reaction. With aromatic and heteroaromatic aldehydes, the alkynylogous aldol reaction with (R)‐DTBM‐SEGPHOS as the ligand proceeded smoothly to furnish the products in excellent regioselectivity with good to high diastereoselectivity and excellent enantioselectivity. In the cases of aliphatic aldehydes, esters of but‐2‐yn‐1‐ol as the substrates and (R,R)‐Ph‐BPE as the ligand were found to be crucial to get good to high regio‐ and diastereoselectivity. The produced chiral 2,3‐allenols are easily transformed into synthetically useful 2‐furanones through cyclization. Finally, the developed method was successfully applied in the rapid synthesis of two chiral intermediates toward the synthesis of two pharmaceutically active compounds that have been proposed for the treatment of neurological disorders.

Efficient synthesis in water of mixed carbonates of cyanohydrins from aromatic aldehydes

An efficient preparation of cyanohydrin ethyl carbonates via cyanocarbonation of aromatic and hetero-aromatic aldehydes with sodium cyanide and ethyl chlorocarbonate using commercial surfactants (5 mol %) in aqueous media at low temperature afforded almost quantitative isolated yields (≥94%) in 30 min. Aromatic aldehydes bearing electron-donating as well as electron-withdrawing groups have been successfully employed without any significant changes. Centrifugation of the reaction mixture allows accessible purification without the need of solvent extraction. Reaction conditions can be readily upscaled to multigrams.

SYNTHESIS AND BIOLOGICAL EVALUATION OF BENZIMIDAZOLE DERIVATIVES AS ANTIMICROBIAL AGENTS

Objective: The present study aims to synthesize and biological evaluation of benzimidazole derivatives as antimicrobial agents.
 Methods: 2-Methylbenzimidazole react with ethyl-chloroacetate gives N1-Ethylacetate-2-methyl-benzimidazole (1), which on reaction with thiosemicarbazide gives N1-acetylthiosemicarbazide-2-methyl-benzimidazole (2). The compound (2) on dehydrative annulation by mineral acid gives N1-(2’-amino-5’-methylene)-1’,3’,4’-thiadiazole-2-methyl-benzimidazole(3), which on condensation with various aromatic and hetero aromatic aldehydes gives N1-(2-substituted-Benzylidene-imino-5’-methylene)-1’, 3’, 4’-Thiadiazole]-2-methyl-benzimidazole(4a-4l).
 Results: The reaction sequence involves microwave-induced preparation of N1-Ethylacetate-2-methyl-benzimidazole (1) from reaction of 2-methylbenzimidazole with ethyl-chloroacetate. Further reaction with thiosemicarbazide gives N1-acetylthiosemicarbazide-2-methyl-benzimidazole (2). The compound (2) on dehydrative annulation by sulfuric acid gives N1-(2’-amino-5’-methylene)-1’,3’,4’-thiadiazole-2-methyl-benzimidazole(3), which on condensation with various aromatic and hetero aromatic aldehydes gives N1-(2-substituted-Benzylidene-imino-5’-methylene)-1’, 3’, 4’-Thiadiazole]-2-methyl-benzimidazole(4a-4l). Which were characterized by IR and 1H NMR spectral data.
 Conclusion: All the synthesized compounds were screened for antimicrobial activity by cup plate method. Most of the derivatives showed good antimicrobial activity against Gram-Positive and Gram-negative bacteria.

ONE-POT SYNTHESIS OF PHTHALAZIN-4-HETEROYL-4H-PYRAN DERIVATIVES IN [BMIM][OH

A [bmim][OH] mediated, green and efficient synthesis of phthalazines derivatives have been developed by condensing phthalic acid (1), ethyl cyanohydrazide (2), heteroaromatic aldehydes (3a-3f) and active methylene compounds (4) at 60-65 oC for 60-90 min. The importance of this method includes shorter reaction time and high yield.

SYNTHESIS, MOLECULAR AND CRYSTALLINE STRUCTURE OF 2-(ALKYLSULFANYL)-4-ARYL(HETARYL)-5,6,7,8-TETRAHYDROQUINOLINE-3-CARBONITRILES

The multicomponent reaction of aromatic and heteroaromatic aldehydes, malonodithioamide, 1-(cyclohex-1-en-1-yl)piperidine, and alkylating reagents was studied. A wide range of new 2-(alkylsulfanyl)-4-aryl(hetaryl)-5,6,7,8-tetrahydroquinoline-3-carbonitriles were synthesized, and their molecular and crystalline structures were studied by X-ray structural analysis.

Microwave-assisted Cannizzaro reaction—Optimisation of reaction conditions

The microwave-assisted Cannizzaro reaction was studied in order to develop fully reproducible synthetic protocols for transformation of aldehydes to carboxylic acid and alcohols. Optimised were the following process parameters: power, temperature, and time. Aromatic, heteroaromatic and aliphatic aldehydes were used in the studies. It was found that furfural, thiophene-2-carbaldehyde, pyridinecarboxaldehyde and aromatic aldehydes react under mild conditions, while 1-methyl-pyrrole-2-carboxaldehyde derivatives and aliphatic aldehydes require more drastic reaction conditions and a longer exposure time to microwave radiation.

An efficient, multicomponent, green protocol to access 4, 7-dihydrotetrazolo [1, 5-a] pyrimidines and 5,6,7,9-tetrahydrotetrazolo[5,1-b]quinazolin-8(4H)-ones using PEG-400 under microwave irradiation

A facile one-pot synthesis of ethyl 5-methyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine, 5-tert-butyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine, 6,6-dimethyl-5,6,7,9-tetrahydrotetrazolo[5,1-b]quinazolin-8(4H)-one and 5,6,7,9-tetrahydrotetrazolo[5,1-b]quinazolin-8(4H)-one derivatives were described via a three-component reaction of aldehyde, 5-aminotetrazole and diketones in PEG-400 under microwave irradiation at 110 °C for 30 min. A wide range of diketones such as ethylacetoacetate, tert-butyl acetoacetate, 5,5-dimethylcyclohexane-1,3-dione and 1,3-cyclohexanedione were utilized to carry out the synthesis of different dihydrotetrazolo[1,5-a]pyrimidines and tetrahydrotetrazolo[1,5-a]quinazolinones. This method has the advantage of green protocol, operational simplicity, high yields, recyclability of the solvent and involves isolation of the final product without column purification. The scope of this reaction tolerates with aromatic, heteroaromatic and alicyclic aldehydes.

Synthesis of Novel N,N′,N″-Tris[aryl(hetaryl)-methylideneamino]guanidine Derivatives as Efficient and Selective Colorimetric Sensors for Fluoride Ion

A series of N,N′,N″-tris[aryl(hetaryl)methylideneamino]guanidines have been synthesized in good yields by condensation of N,N′,N″-triaminoguanidine hydrochloride with aromatic and heteroaromatic aldehydes. All compounds have been characterized by 1H and 13C NMR and FT-IR spectra, and the molecular structure of one compound has been determined by single crystal X-ray diffraction. Study of the optical properties of the title compounds in the presence of fluoride ions has shown selective color change from colorless to yellow and purple due to red shift in their UV-Vis absorption spectra.