From‐Core and From‐End Direct CH Arylations: A Step‐Saving New Synthetic Route to Thieno[3,4‐c]pyrrole‐4,6‐dione (TPD)‐Incorporated D‐‐π–A–π–D Functional Oligoaryls

In contrast to the traditional multistep synthesis, herein an efficient and fewer‐steps new synthetic strategy is demonstrated for the facile preparation of organic‐electronically important D–π–A–π–D‐type oligoaryls through sequential direct C?H arylations. This methodology has shown that the synthesis of thieno[3,4‐c]pyrrole‐4,6‐dione (TPD)‐ or furano[3,4‐c]pyrrole‐4,6‐dione (FPD)‐centred target molecules could be accessed step‐economically either from the core structure (acceptor) or from the end structure (donor), which supplied a more flexible and succinct new synthetic alternative to the preparation of the π‐functional small‐molecule semiconducting materials. In addition, optical and electrochemical properties of the synthesized oligoaryls were examined.     

A Mild Approach to the Synthesis of sn‐Glycerol 1,2‐Di‐γ‐linolenate 3‐Palmitate

A synthetic approach comprising several studied modifications was applied to the preparation of sn‐glycerol 1,2‐di‐γ‐linolenate 3‐palmitate ( 4 ). Thereby, a convenient and mild synthetic method was elaborated, affording 4 from 1,2‐O‐isopropylidene‐sn‐glycerol ( 1 ) in an average yield of 65 – 75% and analytically acceptable purity.     

Study of the Reaction of 5‐Aryl‐7‐hydrazino‐2‐phenylpyra‐zolo[1,5‐c]pyrimidines with 1,3‐Dicarbonyl Compounds

A novel synthetic method for the preparation of 5‐aryl‐7‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐2‐phenylpyrazolo[1,5‐c]‐pyrimidines and 1‐(5‐aryl‐2‐phenylpyrazolo[1,5‐c]pyrimidin‐7‐yl)‐3‐methyl‐1H‐pyrazol‐5‐ols is provided by condensative cyclization of 5‐aryl‐7‐hydrazino‐2‐phenylpyrazolo[1,5‐c]pyrimidines with 1,3‐dicarbonyl compounds. The study of the more reactive position for electrophilic substitusion reactions on such ring system was also achieved.     

Stereoselective Synthesis of α‐3‐Deoxy‐D‐manno‐oct‐2‐ulosonic Acid (α‐Kdo) Glycosides Using 5,7‐O‐Di‐tert‐butylsilylene‐Protected Kdo Ethyl Thioglycoside Donors

An efficient methodology for the synthesis of α‐Kdo glycosidic bonds has been developed with 5,7‐O‐di‐tert‐butylsilylene (DTBS) protected Kdo ethyl thioglycosides as glycosyl donors. The approach permits a wide scope of acceptors to be used, thus affording biologically significant Kdo glycosides in good to excellent chemical yields with complete α‐selectivity. The synthetic utility of an orthogonally protected Kdo donor has been demonstrated by concise preparation of two α‐Kdo‐containing oligosaccharides.     

Synthesis of Poly(2‐oxazoline)‐Based Hydrogels with Tailor‐Made Swelling Degrees Capable of Stimuli‐Triggered Compound Release

A 32‐membered library of poly(2‐oxazoline)‐based hydrogels of the composition p EtOx _m‐p PhOx _n‐p PBO _q (m/n = 150/0, 100/50, 50/100, and 0/150; q = 1.5–30) was prepared from 2‐ethyl‐ ( EtOx ), 2‐phenyl‐2‐oxazoline ( PhOx ), and phenylene‐1,3‐bis‐(2‐oxazoline) ( PBO ). The polymerizations were performed from ground monomer mixtures at 140 °C in a single‐mode microwave reactor in reaction times as short as 1 h. Purified hydrogels, containing no residual monomers, were obtained in yields of 95% or higher. Acid‐mediated hydrolysis rates as well as swelling degrees of the hydrogels were adjustable over a broad range; swelling degrees in water/ethanol/dichloromethane ranged from 0 to 13.8/11.7/20.0. The hydrogels could incorporate organic molecules according to in situ or post‐synthetic routines. Post‐synthetic routines enabled for the preparation of hydrogels from which the incorporated compounds were only released through diffusion processes if the solvent was changed or through hydrogel degradation if the pH was lowered.     

A Facile and One‐pot Synthetic Route to Functionalized Ethyl 3‐(Alkanoyl)‐2‐(alkyl imino)‐2,3‐dihydrothiazole‐4‐carboxylate Derivatives under Mild,Solventand Catalyst‐free Conditions

A new one‐pot, four‐component synthetic rout is reported for the preparation of functionalized N‐acyl‐2alkylimino‐2,3‐dihydrothiazole derivatives from the reaction between acid chlorides, ammonium thiocyanate, primary alkylamines, and ethyl bromopyruvate under mild, solvent‐ and catalyst‐free conditions at room temperature. This completely green and efficient straight forward procedure led to the desired products in good to high yields without any need to catalyst or solvent assistance and no by product was observed in all the reactions     

Synthesis of Functionalized Hemi‐1,2,4‐triazinyl‐[2,2′]‐bipyridines via Telescoped Condensation of [2,2′]‐bipyridinyl‐6‐carbonitrile

Partitioning of neutron‐poisoning lanthanides from minor actinides in used nuclear fuel using liquid–liquid separation techniques with moderately soft Lewis basic heterocyclic scaffolds is an area of intense research focus. Nitrogen heterocycles have demonstrated potential for the selective separation of Am³⁺ from Eu³⁺ in separations processes. Improved synthetic strategies are required to access more diversified complexant scaffolds for further study. The present work describes an efficient synthetic strategy for the preparation of functionalized [2,2′]‐bipyridinyl scaffolds using Pd catalysis to prepare the requisite starting material and telescoped condensation to afford direct access to hemi‐1,2,4‐triazinyl‐[2,2′]‐bipyridines with aliphatic character and potentially greater solubility in less polar diluents. Synthetic method development, optimization, and substrate scope are reported herein.     

Chemoselective Synthesis of Z‐Olefins through Rh‐Catalyzed Formate‐Mediated 1,6‐Reduction

Z‐olefins are important functional units in synthetic chemistry; their preparation has thus received considerable attention. Many prevailing methods for cis‐olefination are complicated by the presence of multiple unsaturated units or electrophilic functional groups. In this study, Z‐olefins are delivered through selective reduction of activated dienes using formic acid. The reaction proceeds with high regio‐ and stereoselectivity (typically >90:10 and >95:5, respectively) and preserves other alkenyl, alkynyl, protic, and electrophilic groups.     

Enantioselective γ‐Addition of Pyrazole and Imidazole Heterocycles to Allenoates Catalyzed by Chiral Phosphine

Chiral phosphines were found to catalyze the enantioselective asymmetric γ‐addition of heteroaromatic compounds to allenoates in good yields with high enantiomeric ratios and regioselectivity in the presence of (S)‐BINOL. Both pyrazole and imidazole could be employed in this process. The synthetic value of these γ‐addition products was demonstrated by the preparation of biologically relevant molecules and structural scaffolds. Remarkably, the synthetic utility of this strategy was demonstrated through a two‐step synthesis of a Janus kinase (JAK) inhibitor.     

Synthesis of 2,3‐Disubstituted 5‐Iodo‐1H‐Pyrrolo[2,3‐b]pyridines via Fischer Cyclization

A simple and convenient procedure for the preparation of some unknown 2,3‐disubstituted 5‐iodo‐1H‐pyrrolo[2,3‐b ]pyridines from readily available starting materials by Fischer indole cyclization in polyphosphoric acid is described. The present methodology provides an alternative synthetic approach to the synthesis of 5‐iodo‐7‐azaindole scaffold. All synthesized compounds were characterized by IR, MS, ¹H and ¹³C NMR, and elemental analysis.     

New and Practical Synthesis of N‐(3‐Cyano‐7‐ethoxy‐4‐oxo‐1,4‐dihydroquinolin‐6‐yl)acetamide

New and practical synthetic route of N‐(3‐cyano‐7‐ethoxy‐4‐oxo‐1,4‐dihydroquinolin‐6‐yl)acetamide ( 1 ) is described, through the cyclization of 2‐aminophenyl‐ethanone ( 12 ) with N,N‐dimethylformamide dimethylacetal. The overall yield of 1 obtained from this process is 46% (five steps) with a purity of >99% (HPLC).     

Total Synthesis of (−)‐Tetrodotoxin and 11‐norTTX‐6(R)‐ol

The enantioselective total synthesis of (−)‐tetrodotoxin [(−)‐TTX] and 4,9‐anhydrotetrodotoxin, which are selective blockers of voltage‐gated sodium channels, was accomplished from the commercially available p ‐benzoquinone. This synthesis was based on efficient stereocontrol of the six contiguous stereogenic centers on the core cyclohexane ring through Ogasawara's method, [3,3]‐sigmatropic rearrangement of an allylic cyanate, and intramolecular 1,3‐dipolar cycloaddition of a nitrile oxide. Our synthetic route was applied to the synthesis of the tetrodotoxin congeners 11‐norTTX‐6(R )‐ol and 4,9‐anhydro‐11‐norTTX‐6(R )‐ol through late‐stage modification of the common intermediate. Neutral deprotection at the final step enabled easy purification of tetrodotoxin and 11‐norTTX‐6(R )‐ol without competing dehydration to their 4,9‐anhydro forms.     

Access to Pyrazolidin‐3,5‐diones through Anodic N–N Bond Formation

Pyrazolidin‐3,5‐diones are important motifs in heterocyclic chemistry and are of high interest for pharmaceutical applications. In classic organic synthesis, the hydrazinic moiety is installed through condensation using the corresponding hydrazine building blocks. However, most N,N′‐diaryl hydrazines are toxic and require upstream preparation owing to their low commercial availability. We present an alternative and sustainable synthetic approach to pyrazolidin‐3,5‐diones that employs readily accessible dianilides as precursors, which are anodically converted to furnish the N?N bond. The electroconversion is conducted in a simple undivided cell under constant‐current conditions.     

Copper‐Mediated Addition of Ethanolamine Affording 2‐Hydroxymethyl Naphtho[2,1‐d]oxazoles from 2‐Naphthols

A new and mild synthetic approach was presented for the synthesis of naphtho[2,1‐d]oxazoles. In the presence of copper (II)‐ethanolamine, 2‐hydroxymethyl naphtho[2,1‐d]oxazoles were one‐pot synthesized in moderate to good yields through copper‐mediated oxidation of 2‐naphthols followed with the addition of ethanolamine in acetonitrile.     

Convenient and Highly Efficient Routes to 2 H‐Chromene and 4‐Chromanone Derivatives: Iodine‐Promoted and p‐Toluenesulfonic Acid Catalyzed Cascade Cyclizations of Propynols

A convenient strategy is presented for the easy preparation of a series of 2 H‐chromenes under mild conditions through iodocyclization of readily accessible propynols. In addition, various 4‐chromanones can be synthesized through a p‐toluenesulfonic acid catalyzed cascade cyclization with high efficiency (yields up to 99 %). Our developed reaction systems are proven to have good functional‐group applicability and can be scaled up to gram quantities in satisfactory yields. These systems also provide a new synthetic strategy for two types of important flavonoid skeleton without using costly and toxic metal catalysts. Additionally, the resulting halides could be further exploited in subsequent palladium‐catalyzed coupling reactions, so these compounds could act as potential intermediates for the construction of some valuable drug molecules.     

Acid Catalyzed tert‐Butylation and Tritylation of 4‐Nitro‐1,2,3‐triazole: Selective Synthesis of 1‐Methyl‐5‐nitro‐1,2,3‐triazole via 1‐tert‐Butyl‐4‐nitro‐1,2,3‐triazole

4‐Nitro‐1,2,3‐triazole was found to react with tert‐butanol in concentrated sulfuric acid to yield 1‐tert‐butyl‐4‐nitro‐1,2,3‐triazole as the only reaction product, whereas tert‐butylation and tritylation of 4‐nitro‐1,2,3‐triazole in presence of catalytic amount of sulfuric acid in benzene was found to provide mixtures of isomeric 1‐ and 2‐alkyl‐4‐nitro‐1,2,3‐triazoles with predominance of N2‐alkylated products. A new methodology for preparation of 1‐alkyl‐5‐nitro‐1,2,3‐triazoles from 1‐tert‐butyl‐4‐nitro‐1,2,3‐triazole via exhaustive alkylation followed by removal of tert‐butyl group from intermediate triazolium salts was demonstrated by the example of preparation of 1‐methyl‐5‐nitro‐1,2,3‐triazole.     

A Convenient Synthesis of 1‐Alkoxy‐2‐alkyl‐1,2‐dihydroisoquinoline‐3,4‐diones Utilizing the Reaction of 2‐(Dialkoxymethyl)phenyllithiums with Dimethyl Oxalate

A new and convenient method for the preparation of 1,2‐dihydroisoquinoline‐3,4‐diones with alkoxy and alkyl groups at the 4‐ and 3‐positions, respectively, using an easily operated three‐step sequence starting from 2‐(dialkoxymethyl)phenyl bromides has been developed. Thus, the starting materials are treated with BuLi to generate 2‐(dialkoxymethyl)phenyllithiums, which are allowed to react with (COOMe)₂ to give methyl 2‐(dialkoxymethyl)phenyl‐2‐oxoacetates. These are then transformed into the corresponding secondary amides by the reaction with primary amines. Treatment of these keto amides with a catalytic amount of TsOH?H₂O affords the desired products. In order to demonstrate the synthetic utility of these products, transformation of one of them into the corresponding isoquinoline‐1,3,4(2H)‐trione derivative by the oxidation with PCC was achieved.     

5‐(2‐Mercaptoethyl)‐1H‐tetrazole: Facile Synthesis and Application for the Preparation of Water Soluble Nanocrystals and Their Gels

A facile method for the preparation of the novel capping ligand 5‐(2‐mercaptoethyl)‐1H‐tetrazole for the stabilization of water‐soluble nanocrystals was developed. This effective synthetic procedure is based on the cycloaddition of sodium azide to 3,3′‐dithiobis(propionitrile) followed by the reductive cleavage of a S?S bond with triphenylphosphine. The structure of the synthesized compound was confirmed by single‐crystal X‐ray analysis. A target tetrazole was successfully applied for the direct aqueous synthesis of CdTe and Au nanocrystals. CdTe nanocrystals capped with 5‐(2‐mercaptoethyl)‐1H‐tetrazole were found to reveal high photoluminescence efficiencies (up to 77 %). Nanocrystals capped with this tetrazole ligand are able to build 3D structures in a metal‐ion‐assisted gelation process in aqueous solution. Critical point drying of the as‐formed hydrogels allowed the preparation of the corresponding aerogels, while preserving the mesoporous structure.     

Synthesis of 2‐Mercaptobenzaldehyde, 2‐Mercaptocyclohex‐1‐enecarboxaldehydes and 3‐Mercaptoacrylaldehydes

A novel one‐pot approach for the preparation of 2‐mercaptobenzaldehyde, 2‐mercaptocyclohex‐1‐enecarboxaldehydes and 3‐mercaptoacrylaldehydes [(Z)‐3‐mercapto‐2‐methyl‐3‐phenylacrylaldehyde, 3‐mercapto‐3‐(o‐tolyl)acrylaldehyde)] starting from ortho‐bromobenzaldehyde, 2‐chlorocyclohex‐1‐enecarbaldehydes, (Z)‐3‐chloro‐2‐methyl‐3‐phenylacrylaldehyde and 3‐chloro‐3‐(o‐tolyl)acrylaldehyde is reported. The reaction of sulfur with the Grignard reagent of the acetal for the protection of the aldehyde group affords the title compounds through hydrolysis with dilute hydrochloric acid in high yields.     

Application of bromoacetate‐substituted β‐CD‐bonded silica particles as chiral stationary phase for HPLC

Bromoacetate‐substituted [3‐(2‐O‐β‐cyclodextrin)‐2‐hydroxypropoxy]propylsilyl‐appended silica particles (BACD‐HPS), an important and useful synthetic intermediate for preparation of novel types of macrocycles‐capped β‐CD‐bonded silica particles including crown ether/cyclam/calix[4]arene‐capped β‐CD‐bonded silica particles, have been prepared and used as chiral stationary phase for HPLC. This synthetic stationary phase is characterized by means of elemental analysis. For the first time, the chromatographic behavior of BACD‐HPS was systematically evaluated with several disubstituted benzenes and some chiral drug compounds under both normal and RP conditions in HPLC. The results show that BACD‐HPS has excellent selectivity for the separation of aromatic positional isomers and chiral isomers of some drug compounds when used as stationary phase in HPLC.