Aldehydes 2a Research Articles

Stereoselective Synthesis of (Z)-1-Benzhydryl-4-cinnamylpiperazines via the Wittig Reaction

A synthetic method of producing (E)- and (Z)-isomers of 1-benzhydryl-4-cinnamylpiperazines in a specific ratio from corresponding benzhydrylpiperazine is described. Of the three compounds synthesized (5a–c), the ratio of E/Z-isomers remained around 15:85. The key intermediates, 1-benzhydryl-4-(2,2-dimethoxyethyl)piperazine derivatives (3a–c), were prepared by nucleophilic substitution reaction of benzhydrylpiperazines (2a–c) with chloroacetaldehyde dimethylacetal in good yield (up to 88%). Hydrolysis of 3a–c gave the corresponding aldehydes 4a–c, which when subjected to the Wittig reaction followed by column purification to afford 1a–c (E-isomers) and 6a–c (Z-isomers) in pure form. The isolated compounds were characterized by NMR and mass spectral analysis. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

Water mediated synthesis, spectral and structural studies of ethyl 6-amino-4-aryl-5-cyano-2-propyl-4H-pyran-3-carboxylates: Single crystal X-ray structure of ethyl 6-amino-4-(2-chlorophenyl)-5-cyano-2-propyl-4H-pyran-3-carboxylate

An efficient and multifunctional three component synthetic protocol was developed to synthesize ethyl 6-amino-4-aryl-5-cyano-2-propyl-4H-pyran-3-carboxylates from ethyl 3-oxohexanoate, malononitrile and corresponding aldehydes (1a–11a) using K2CO3 as a catalyst under water solvent in good yields. The derived compounds have been analyzed by IR and NMR (1D and 2D) spectra. Single crystal X-ray structural analysis of 2a, evidences the flattened-boat conformation of pyran ring and the phenyl group is nearly perpendicular to the pyran ring.

A practical procedure of low valent tin mediated Barbier allylation of aldehydes in wet solvent

Use of aluminium as the reducing metal in spontaneous bimetal redox reaction has been elegantly exploited for allylation/crotylation of aldehydes in wet solvent. Here, low valent tin was prepared in situ by reduction of SnCl2·2H2O with aluminium in THF/water. The resulting low valent tin acted as an efficient mediator for allylation and crotylation of aldehydes (3a–q) producing the corresponding homoallylic alcohols. The efficacy of this procedure was due to its operational simplicity, practical viability, inexpensiveness, good yields of the products and short reaction time.

Expeditious synthesis of bicyclic pyrrolidine/pyrrolizidine/thiazolidine grafted macrocycles through intramolecular 1,3-dipolar cycloaddition of azomethine ylides

Stereoselective synthesis of bicyclic pyrrolidine and pyrrolizidine grafted macrocycles has been accomplished through intramolecular 1,3-dipolar cycloaddition (1,3-DC) reaction. Alkenyl aldehydes 4a–b derived from salicylaldehyde have been reacted with secondary aminoacids to generate azomethine ylides which in turn were trapped intramolecularly by suitably placed dipolarophiles to give the corresponding macrocycle in moderate yield. The structures were assigned by 2D NMR spectra and the regio- and stereochemical outcome of the cycloadducts was established by a single crystal X-ray analysis of one of the products.

New route for synthesis, spectroscopy, and X-ray studies of 2-[aryl-(6′-hydroxy-4′,4′-dimethyl-2′-oxocyclohex-6′-enyl)methyl]-3-hydroxy-5,5-dimethylcyclohex-2-enone and 1,8-dioxo-octahydroxanthenes and antitumor evaluation

Treatment of 1-(benzothiazol-2-yl-thio)-acetonitrile 1 with 5,5-dimethyl-1,3-cyclohexanedione-(dimedone) 2 and aromatic aldehyde 3a, b in refluxing ethanol containing a catalytic amount of piperidine lead to bisdimedone derivatives 5a and b in short periods of times with excellent yields and not 4H-chromen-5(6H)-one derivatives 8. The compound 5a was then cyclized to 1,8-dioxo-octahydroxanthene derivative 6. The structures of the synthesized compounds were elucidated by elemental analysis 1H NMR and 13C NMR spectra, COSY, HSQC, HMBC, MS, and X-ray crystallographic investigations. The cytotoxicity of the synthesized compounds 5a, b, and 6 were studied and evaluated. Three human tumor and three normal cell lines, namely as breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268), human fibroblast (WI-38), normal prostate epithelial cells, and normal colon mucosal, NCM 460 cells, respectively. The tested compounds were found to exhibit higher inhibitory effects toward the tumor and normal cell lines than the reference drug, doxorubicin.

Selective synthesis of 4,5-dihydroimidazo- and imidazo[1,5-a]quinoxalines via modified Pictet–Spengler reaction

An efficient tandem approach for the selective synthesis of 4,5-dihydroimidazo[1,5-a]quinoxalines 6a–g and imidazo[1,5-a]quinoxalines 7a–h by the reaction of 2-imidazolyl anilines 4a–c with aryl aldehydes 5a–k under mild reaction conditions is described. Introduction of electron releasing alkyl groups in substrates 4a–b was found to be instrumental for the success of the reaction.

Microwave Assisted Synthesis of Biologically Active α-Aminophosphonates Catalyzed by Nano-BF3·SiO2 under Solvent-Free Conditions

An efficient and high-yield synthesis of a class of new α-aminophosphonate derivatives as diethyl α-aryl/2-thienyl-α-[2-(phenylthio)phenylamino]methylphosphonates 6a–j in short reaction times from three component coupling reactions (Kabachnik-Fields reaction) of 2-aminodiphenylsulfide 3, substituted phenyl/heterocyclic aldehydes 4a–j, and diethyl phosphite 5 is reported. The reaction proceeds smoothly in the presence of the catalyst, nano-silica-supported boron trifluoride (BF3·SiO2) without using solvent under microwave irradiation. The title compounds were tested for in vitro antibacterial and antifungal activities at concentrations of 100 and 200 μg/disc. Minimum inhibitory concentrations (MICs) were also examined. Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures and tables.

Lipase-catalyzed preparation of optically active isomers of cyclamen aldehyde

Abstract The optically active isomers of cyclamen aldehyde 1a were synthesized from a chiral intermediate prepared by lipase-catalyzed enantioselective transesterification of a prochiral diol with vinyl acetate. The absolute configuration of the enantiomer of 1a with dextrorotatory in chloroform was determined to be ( S )-configuration. The results of an olfactory evaluation of the prepared isomers are also reported.

On Water: Silver-Catalyzed Domino Approach for the Synthesis of Benzoxazine/Oxazine-Fused Isoquinolines and Naphthyridines from o-Alkynyl Aldehydes

An operationally simple domino approach for the silver-catalyzed synthesis of oxazine/benzoxazine-fused isoquinolines 5a-q and naphthyridines 6a-v by the reaction of o-alkynyl aldehydes 3a-aa with amines having embedded nucleophiles 4a-d under mild reaction condition in water is described. The reaction shows selective C-N bond formation on the more electrophilic alkynyl carbon resulting in the formation of 6-endo-dig cyclized product. The competitive experiments show the viability of an intramolecular nucleophilic attack over an intermolecular attack of the external nucleophile. This methodology accommodates wide functional group variation, which proves to be useful for structural and biological assessment.

Intramolecular Cyclization of Arylalkynes with C‐O Bond Formation on Ruthenium Complexes

AbstractCyclization of terminal arylalkynes containing aldehyde (1a), ketone (1b‐c) or hydroxyl (6a‐c) functionality on the aryl ring induced by ruthenium complex is investigated. For the reaction of Cp(PPh3)2RuCl with o‐ethynyl benzaldehyde 1a, a vinylidene intermediate was formed which is followed by a carbonyl attack to give 2a. However, for 1b‐c, with a ketone replacing the aldehyde group, isobenzofuryl carbene complexes (4b‐c) were formed as the major products along with the isochromene carbene complexes (2b‐c) as the minor products. For three o‐enynyl phenol compounds 6a‐c with different substituents on the aryl ring, the reactions take place at the triple bond first giving vinylidene intermediates which undergo facile intramolecular cyclization to yield the cyclic oxocarbene complexes 7a‐c in excellent yields. Modification of various substituents at Cβ of the carbene ligand of 7 by the use of different alkyl halides can be readily achieved under mild condition. For the chromane ring derivatives 11, the two allyl groups underwent ring closing metathesis reaction in the presence of Grubb's catalyst and yielded the tricyclic product 12. These chemical reactions and their mechanisms are corroborated by structure determinations of two ruthenium complexes using single crystal X‐ray diffraction analysis.

ChemInform Abstract: Synthesis of Tetrahydro‐3‐benzazepines.

Abstract A synthetic route toward tetrahdro-3-benzazepines 1a – f starting with 2a and 2b in modest total yield is described. The facile route was carried by Henry reaction of aldehydes 3a – e with nitroalkanes and NH 4 OAc at reflux, reduction of the resulting nitroalkenes 4a – h with LAH at rt followed by protection with K 2 CO 3 and PhSO 2 Cl at rt, one-pot oxidative cleavage annulation of olefins 5a – h with the one-pot combination of OsO 4 /NaIO 4 at reflux, and hydrogenation of the corresponding enamines 6a – f . Aldehydes 3a – e was prepared from 2a and 2b in moderate yield of three-step.

Synthesis of some 2, 6-bis (1-coumarin-2-yl)-4-(4-substituted phenyl) pyridine derivatives as potent biological agents

A convenient one-pot, three-component synthesis of 2, 6-bis (1-coumarin-2-yl)-4-(4-substituted phenyl) pyridine derivatives (3a–k) by Chichibabin reaction has been reported. These compounds were synthesized by the reaction of 3-acetyl coumarin (1a) or 5-bromo 3-acetyl coumarin (1b) with substituted aromatic aldehydes (2a–k) and ammonium acetate under acidic conditions and the structure was confirmed by FT-IR, 1H NMR, 13C NMR and Mass spectroscopic methods. The newly synthesized compounds (3a–k) were evaluated for antimicrobial activity, DPPH free radical scavenging activity and ferrous ion-chelating ability. The mode of action of these active compounds was carried out by docking receptor GlcN6P synthase. Compounds 3a, 3b, 3c, and 3d have displayed potential antimicrobial activity and some of the compounds have shown promising antioxidant properties.

Two efficient methods for the synthesis of novel indole-based chalcone derivatives

Two powerful methods for the synthesis of indole-based chalcone derivatives, namely (E)-1-(2-chloro-1-(4-chlorobenzyl)-1H-indol-3-yl)-3-aryl(hetaryl)prop-2-en-1-ones (3a–l), are described, involving the ultrasound-assisted or solvent-free Claisen–Schmidt condensation reaction of 3-acetyl-2-chloro-1-(4-chlorobenzyl)indole (1) and various aromatic aldehydes (2a–l). The ultrasound-assisted Claisen–Schmidt condensation reaction was carried out using 1,4-dioxane as solvent and KOH as base at room temperature to give the corresponding products (3a–l) in yields ranging from 75 to 88 %. Alternatively, the Claisen–Schmidt condensation reaction could also be conducted under solvent-free conditions to obtain the products (3a–l) in comparable yields. The two procedures offer easy access to indole-based chalcone derivatives in short reaction times and good yields under mild conditions. Particularly, the advantageous aspect of the solvent-free method could avoid the use of environmentally hazardous and toxic solvents, and also reduced costs. The structures of all the newly synthesized indole-based chalcones 3a–l were confirmed by spectral data and elemental analyses.

Three-component synthesis of tetrazolo-pyrimidines annelated by C6 to C8 carbocycles

By treatment of 3-amino-4H-1,2,4-triazole and 5-amino-1H-tetrazole with -unsaturated ketones of cyclohexanone series, we have previously obtained linearly structured azoloquinazolines with an admixture of isomers with angular ring fusion [1]. Extension of this reaction to ylidenecyclohexanone analogs with a greater size of alicycle (C7, C8) was not appropriate due to their low yields. Bearing in mind the importance of substituted azolopyrimidines in the search for novel biologically active materials and the successful use of multicomponent reactions [2, 3] for heterocycle synthesis, we have studied the possibility of using three-component cyclocondensation for synthesis of tetrazolopyrimidines annelated by C6 to C8 carbocycles. The reactions were carried out by refluxing equimolar amounts of the 5-amino-1H-tetrazole, the aldehyde 1a,b (furfural, benzaldehyde), and ketone 2a-c (cyclohexanone, cycloheptanone, cyclooctanone). As a result, the partially reduced cyclanotetrazolopyrimidines 3a-f were obtained in 39-68% yields.

Microwave‐Assisted Rapid Synthesis of Novel 1,5‐Benzodiazepine Derivatives as Potent Antimicrobial Agent

A new series of highly functionalized 1,5‐benzodiazepine derivatives 5a–x have been synthesized from 3‐[(1E)‐N‐(2‐aminophenyl) ethanimidoyl]‐4‐hydroxyl‐2H‐chromen‐2‐one 3a–c and pyrazole aldehyde 4a–h using catalytic amount of triflouro acetic acid under microwave irradiation. The main significant of the present procedure is shorter reaction time, easy work up procedure, and excellent yield with high purity. The structures of all the compounds were established on the basis of their IR, NMR, and mass spectral data and have been screened for their antimicrobial activity and antifungal activity.

Synthesis of β-amino carbonyl derivatives of coumarin and benzofuran and evaluation of their biological activity

A series of β-amino carbonyl compounds containing coumarin (4a–h) and benzofuran (6a–i) moieties was synthesized by a three component Mannich reaction of 3-acetyl-2H-chromen-2-one (1) or 1-(1-benzofuran-2-yl) ethanone (5) with p-substituted aromatic aldehydes (2a–g) and aromatic amines (3a–b) in the presence of cerric ammonium nitrate as a catalyst. The newly synthesized compounds were screened for antimicrobial and antioxidant activities. Compounds 4b, 4e, 4f, 6f, 6g, and 6i showed microbial inhibition with minimal inhibition concentration ranging between 0.040 and 0.500 mg/mL, compounds 4b, 4c, 6c, 6e, and 6i showed promising free radical scavenging activity and compounds 4b, 4f, 6c, 6d, and 6h showed good chelating ability with Fe2+ ions. The synthesized compounds were studied for docking on the enzyme, glucosamine-6-phosphate synthase to predict the binding affinity and orientation at the active site of the receptor.

A simple and efficient procedure for synthesis of symmetrical bis(4-amino-4H-1,2,4-triazole-5-thiols)

Abstract A series of bis(1,2,4-triazole-3-thiols) 3a–d were prepared by condensation reactions of arylbis(carboxymethylthio)methanes 2a–d with thiocarbohydrazide. The starting diacids 2a–d were prepared by reactions of aromatic aldehydes 1a–d with thioglycolic acid. The structures of these newly synthesized compounds are characterized by elemental analysis, IR, and NMR spectroscopy.

Syntheses of some novel and symmetrical bis(4-amino-4H-1,2,4-triazole-3-thiols)

A series of bis(4-amino-4H-1,2,4-triazole-3-thiols) 3a–e were prepared by condensation reactions of 2,2′-(phenylmethylene)bis(sulfanediyl)diacetic acids 2a–e with thiocarbohydrazide. The starting diacid 2a–e was prepared by reactions of aromatic aldehydes 1a–e with 2-mercaptoacetic acid. The structures of these newly synthesized compounds are characterized by elemental analysis, and infrared and NMR spectroscopy.

Synthesis of tetrahydro-3-benzazepines

A synthetic route toward tetrahdro-3-benzazepines 1a–f starting with 2a and 2b in modest total yield is described. The facile route was carried by Henry reaction of aldehydes 3a–e with nitroalkanes and NH4OAc at reflux, reduction of the resulting nitroalkenes 4a–h with LAH at rt followed by protection with K2CO3 and PhSO2Cl at rt, one-pot oxidative cleavage annulation of olefins 5a–h with the one-pot combination of OsO4/NaIO4 at reflux, and hydrogenation of the corresponding enamines 6a–f. Aldehydes 3a–e was prepared from 2a and 2b in moderate yield of three-step.

Synthesis of β-ionone derived chalcones as potent antimicrobial agents

A series of chalcones (3a–v) have been synthesized by condensation of β-ionone (1) with a variety of aldehydes (2a–v). The synthesized compounds have been screened for their in vitro antimicrobial activity against five bacterial and five fungal strains, using disc diffusion assay. The evaluated compounds display a wide range of activities, from completely inactive to the highly active compounds. Some of the compounds are also active against methicillin resistant staphylococcus aureus (MRSA).