Development in Synthesis,Electrochemistry, LB Moieties of Phenothiazine Based Units

A convenient and higher yielding synthetic route to N‐alkyl‐bis(thiophene)phenothiazine derivatives is reported and their aggregation, electrochemical properties and polymerization are characterized. The key step in the synthesis of this group of compounds has been the Stille type coupling reaction between the N‐alkyldibromophenothiazine and tin derivatives of thiophene as the best way for preparation of conjugated N‐alkylphenothiazine derivatives. For this group of compounds we also present an electrochemical polymerization effect and widely adopted approach to prepare structurally ordered thin, electroconducting films by Langmuir–Blodgett technique.     

High regioselectivity in electrochemical α-methoxylation of N-protected cyclic amines

N-Protecting groups of α-substituted cyclic amines strongly affected the regioselectivity in electrochemical methoxylation of these compounds. Namely, N-acyl derivatives were transformed into α′-methoxylated compounds, while N-cyano derivatives changed into α-methoxylated derivatives. Furthermore, Lewis acid catalyzed nucleophilic substitution of the α-methoxylated compounds protected with cyano group afforded α,α-disubstituted cyclic amines.     

π-Olefin-Iridium-Komplexe XVI. Bis(η4-cyclohexa-1,3-dien)iridium-2-furyl-, -2-thienyl- und -2-N-methylpyrrolyl-Verbindungen

The reactions of (chd)₂IrCl (chd = η⁴-cyclohexa-1,3-diene) with the 2-lithio derivatives of furane, thiophene, and N-methylpyrrole in ether give the corresponding (chd)₂Ir-2-furyl, -2-thienyl-, and -2-N-methylpyrrolyl complexes, respectively. The new compounds have been characterized by elemental analysis, mass and NMR spectroscopy.     

Crystal structure and reactivity of 2-chloro-3,5-dinitrothiophene and of 2-phenylsulphonyl-3,5-dinitrothiophene with nucleophiles

The geometry obtained by a crystal structure determination of the title compounds, as compared with that of the analogous benzene derivatives, along with results of ab initio calculations, is used to interpret the different S_NAr reactivities in some thiophene and benzene compounds. The smaller rotation of the nitro groups with respect to the aromatic rings observed in thiophene derivatives should be considered a relevant factor in the higher reactivity in the thiophene series.     

Intramolecular cyclisation of functionalised heteroaryllithiums. Synthesis of novel indolizinone-based compounds

The intramolecular cyclisation of heteroaryllithiums derived from N-heteroarylmethylpyrrole-2-carboxamides takes place smoothly at low temperature when N-methoxy-N-methyl and morpholine amides are used as internal electrophiles. Halogen-lithium exchange using n-BuLi is the method of choice to achieve metalation on the quinoline and pyridine derivatives, while directed lithiation (LDA) works better for furan. In the case of thiophene both methodologies can be applied. These metalation-cyclisation sequences provide a useful entry to several types of indolizidine based compounds (pyrrolo[1,2-b]acridinones, pyrrolo[1,2-g]quinolones, thieno and furo[3,2-f]indolizinones).     

Fluoroketenes VIII. Adducts of perfluoromethacryloyl fluoride with unsaturated molecules. N-alkyl-bis(trifluoromethyl)ketenimines

Perfluoromethacryloyl fluoride has been found to yield predominantly 1,4 cyclo-adducts with olefins, isocyanates, nitriles and ketenes. With olefins and isocyanates, 1,2 cyclo-adducts and open-chain adducts are also formed, and evidence is presented to indicate that such adducts are obtained via dipolar intermediates. A new synthesis of N-alkyl-bis(trifluoromethyl)ketenimines is also reported.     

Synthesis and intramolecular cyclization of novel β,β-bis-(benzo[b]thienyl)dehydroalanine derivatives

The methyl ester of tert-butyloxycarbonyl-β,β-dibromodehydroalanine was obtained in a one-pot procedure from bis-(N-tert-butyloxycarbonyl)dehydroalanine. The former was reacted with several boronic benzo[b]thiophene acids under Suzuki cross coupling conditions, to give new β,β-bis-(benzo[b]thienyl)dehydroalanines in high yields. These compounds were cyclized to pyrrole derivatives by treatment with Pd(OAc)₂ and Cu(OAc)₂ in DMF.     

Recent advances in the synthesis of benzo[b]thiophene fused polycyclic derivatives: Strategies and reactions

Benzo[b]thiophene fused compounds with a unique active heterocyclic skeleton have wide applications in the fields of medicinal chemistry, organic synthesis, and organic functional materials, which resulted in rapid development of many efficient methods for the construction of benzo[b]thiophene-fused heterocycles in recent years. Among these methods, the domino reaction of benzo[b]thiophene derivatives is a practical and powerful synthetic route to access benzo[b]thiophene-fused heterocycles by virtue of the particularity of sulfur atom. This review summarizes the latest developments in the construction of benzo[b]thiophene-fused heterocycles by ring formation at the C2-C3-position of benzo[b]thiophene derivatives in the past decade. Additionally, this review is divided into four parts according to the four kinds of benzo[b]thiophene derivatives used, including thioaurone, thioisatin, substituted benzo[b]thiophene, and azadiene.     

Synthesis of novel thienonorbornylpurine derivatives

The synthesis and antiviral evaluation of 6-amino- and 6-chloro-9-(exo-bicyclo[2.2.1]hept-2yl)-9H-purine derivatives with thiophene and tetrahydrothiophenes annelated to a norbornane moiety are described. The key step in the synthesis of derivatives with the symmetrically annelated thiophene was the Mitsunobu reaction of endo-4-thiatricyclo[5.2.1.0^2,6]deca-2,5-dien-8-ol with 6-chloropurine. The key alcohol was obtained by DDQ mediated aromatization of the corresponding tetrahydro derivatives, which were used for the preparation of the target tetrahydrothieno analogs. The key intermediate for the synthesis of derivatives with the asymmetrically annelated thiophene was 8-exo-azido-3-thiatricyclo[5.2.1.0^2,6]deca-2(6),4-diene, which was prepared from 5-exo-azido[2.2.1]heptan-2-one by aldol condensation with O-ethyl S-(2-oxoethyl) carbonodithioate, deprotection and cyclization. The target compounds were obtained by the construction of the purine base on an amine, which was obtained by LAH reduction of the key azide. The synthesized compounds were evaluated for antiviral and cytostatic activity.     

Electrochemically mediated decarboxylative acylation of N-nitrosoanilines with α-oxocarboxylic acids

An efficient palladium-catalyzed electrooxidation C–H acylation reaction of N-nitrosoanilines with α-oxocarboxylic acids was developed. The anodic oxidation of the Pd(Ⅱ) intermediate was found to be the key to complete the reaction. In this case, the N-nitroso group was observed to be an effective directing group for C–H activation reaction. Moreover, the synthetic transformation of derivatives of natural products(L-menthol, dehydroepiandrosterone, and pregnenolone) was successfully realized. Fi...     

Optical and electrochemical properties of novel fused tricyclic thiophene–15-crown-5 systems and their complexes with Mg and Ba ions

New polycyclic aromatic derivatives annulated both with thiophene and with 15-crown-5 ether moieties, crown naphthothiophenes, were synthesized via the Mallory photocyclization with the use of iodine as the mild oxidizer, while two isomeric products were readily separated by column chromatography. Their complexation with Ba²⁺ and Mg²⁺ cations was examined by both optical and electrochemical methods. Spectroelectrochemical studies indicate that the obtained compounds, depending on their structure, can be chemically stable in the oxidized state     

Synthesis of functionalized core-modified sapphyrins and covalently linked porphyrin–sapphyrin dyads

We adopted simple synthetic strategy to synthesize mono-functionalized thiasapphyrins containing functionalized aryl group in the meso-position at thiophene side. The thiasapphyrin building block containing iodophenyl functional group was coupled with three different porphyrin building blocks with N₄, N₃S and N₂S₂ cores containing meso-ethynylphenyl functional group under mild Pd(0) coupling conditions to synthesize three covalently linked diphenyl ethyne bridged porphyrin–thiasapphyrin dyads. The porphyrin–thiasapphyrin dyads were characterized by mass, NMR, absorption, electrochemical and fluorescence techniques. The NMR, absorption and electrochemical studies indicated that the two components in dyads interact weakly and retain their individual identities. The steady state fluorescence studies indicated that the porphyrin fluorescence is reduced to a significant extent because of energy and/or electron transfer to the thiasapphyrin unit. The protonation studies indicated that N₄ porphyrin unit is more basic, whereas N₃S and N₂S₂ porphyrin units are less basic compared to thiasapphyrin unit in respective dyads. We explored the potential of dyads as fluorescent anion sensors and showed that two out of three dyads can be used as fluorescent anion sensors.     

Sulfur-functionalized N-heterocyclic carbenes and their transition metal complexes

Donor group functionalized N-heterocyclic carbenes (NHC) are an important class of ligands used in transition metal complex chemistry. Herein, the growing field of sulfur-functionalized NHC compounds and their respective transition metal complexes are described comprehensively. The sulfur-functionalized NHC compounds are categorized by functional groups such as thiolate, thioether, sulfoxide, thiophene, sulfonate and sulfonamide. Chiral compounds and the hemilabile behaviour of sulfur-functionalized NHC compounds are reported.     

New B-substituted derivatives of m-carborane, p-carborane, and cobalt bis(1,2-dicarbollide) anion

The Pd-catalyzed cross-coupling reactions of B-I bond in m- and p-carboranes and cobalt bis(1,2-dicarbollide) anion with organomagnesium and organozinc compounds were studied. Carboranyl derivatives of furan, thiophene, indole, pyridine and quinoline were synthesized. 2-Pyridylethynyl and 3-quinolylethynyl derivatives of p-carborane were prepared by Pd-catalyzed cross-coupling reactions using corresponding alkynes or their magnesium derivatives.     

Reactions of enaminones and related compounds with N,N-dimethylacetamide dimethyl acetal. A simple one-pot metal-free synthesis of polysubstituted benzene derivatives

Herein a simple one-pot metal-free synthesis of alkyl-, aryl-, heteroaryl- and alkoxycarbonyl substituted 1,3-bis(dimethylamino)benzene derivatives is described. The products were prepared from the corresponding methyl ketones or compounds with an α-methylene group in regard to the carbonyl group, using N,N-dimethylacetamide dimethyl acetal (DMADMA) as the reagent.     

Synthesis of conjugated 2 and 2,5-(ethenyl) and (ethynyl)phenylethynyl thiophenes: fluorescence properties

Nano conjugated thienylethenyl and thienylethynyl compounds with controlled structure and dimensions have been efficiently prepared, by heterocoupling reaction between 1,4-(thienylethynyl)phenylacetylene (or thienylethenyl)phenylacetylene and 2- or 2,5-dihalothiophene. Conjugated 1,4-di(2-thienylethynylphenyl)- (or 2-thienylethenylphenyl)-1,3-butadiyne were obtained by the homocoupling of the terminal acetylenes in excellent yield. The end-capped (N,N-dimethylaminophenyl)- and [3,5-di(trimethylsilylethynyl)-1-ethynyl]-2,5-di(phenylethynyl)_nthiophene were obtained by the heterocoupling between the corresponding terminal acetylene and 2,5-di(iodo)thiophene, catalyzed by the bis(triphenylphosphine)palladium and cuprous iodide system in excellent yield.     

Zinc-Chelating Compounds as Inhibitors of Human and Bacterial Zinc Metalloproteases

Inhibition of bacterial virulence is believed to be a new treatment option for bacterial infections. In the present study, we tested dipicolylamine (DPA), tripicolylamine (TPA), tris pyridine ethylene diamine (TPED), pyridine and thiophene derivatives as putative inhibitors of the bacterial virulence factors thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) and the human zinc metalloproteases, matrix metalloprotease-9 (MMP-9) and matrix metalloprotease-14 (MMP-14). These compounds have nitrogen or sulfur as putative donor atoms for zinc chelation. In general, the compounds showed stronger inhibition of MMP-14 and PLN than of the other enzymes, with K_i values in the lower μM range. Except for DPA, none of the compounds showed significantly stronger inhibition of the virulence factors than of the human zinc metalloproteases. TPA and Zn230 were the only compounds that inhibited all five zinc metalloproteinases with a K_i value in the lower μM range. The thiophene compounds gave weak or no inhibition. Docking indicated that some of the compounds coordinated zinc by one oxygen atom from a hydroxyl or carbonyl group, or by oxygen atoms both from a hydroxyl group and a carbonyl group, and not by pyridine nitrogen as in DPA and TPA.     

Synthesis and Reactions of Some Heterocyclic Candidates Based on 2‐Amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene Moiety as Anti‐Arrhythmic Agents

In continuation of our previous work, a series of novel thiophene derivatives 4 , 5 , 6 , 8 , 9 , 9a , 9b , 9c , 9d , 9e , 10 , 10a , 10b , 10c , 10d , 10e , 11 , 12 , 13 , 14 , 15 , 16 were synthesized by the reaction of ethyl 2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carboxylate ( 1 ) or 2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carbonitrile ( 2 ) with different organic reagents. Fusion of 1 with ethylcyanoacetate or maleic anhydride afforded the corresponding thienooxazinone derivative 4 and N‐thienylmalimide derivative 5 , respectively. Acylation of 1 with chloroacetylchloride afforded the amide 6 , which was cyclized with ammonium thiocyanate to give the corresponding N‐theinylthiazole derivative 8 . On the other hand, reaction of 1 with substituted aroylisothiocyanate derivatives gave the corresponding thiourea derivatives 9a , 9b , 9c , 9d , 9e , which were cyclized by the action of sodium ethoxide to afford the corresponding N‐substituted thiopyrimidine derivatives 10a , 10b , 10c , 10d , 10e . Condensation of 2 with acid anhydrides in refluxing acetic acid afforded the corresponding imide carbonitrile derivatives 11 , 12 , 13 . Similarly, condensation of 1 with the previous acid anhydride yielded the corresponding imide ethyl ester derivatives 14 , 15 , 16 , respectively. The structures of newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, MS spectral data, and elemental analysis. The detailed synthesis, spectroscopic data, LD₅₀, and pharmacological activities of the synthesized compounds are reported.     

Uses of ethyl benzoyl acetate for the synthesis of thiophene,pyran, and pyridine derivatives with antitumor activities

The N-(arly)propanamide derivatives 3a,b were used for a series of heterocyclization reactions to give thiophene, pyran, and pyridine derivatives. Thus, these compounds underwent the Gewald's thiophene synthesis through their reactions with either malononitrile or ethyl cyanoacetate and elemental sulfur to afford compounds 6a-f , respectively. In addition, they were subjected through a series of multicomponent reactions (MCRs) to give pyran and fused derivatives. The reactions of 3a,b with either malononitrile or ethyl cyanoacetate gave pyridine derivatives 14a-d , respectively. The latter compounds afforded arylhydrazone derivatives 15a-m through their reactions with any of the aromatic diazonium salts 15a-c . The antitumor of the synthesized compounds against A549 (nonsmall cell lung cancer), H460 (human lung cancer), HT-29 (human colon cancer), and MKN-45 (human gastric cancer cancer) cancer cell lines together with foretinib as the positive control by a MTT assay was measured, and the results obtained showed that many compounds exhibited high potency against the six cancer cell lines.     

Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives

The novel 1,4-dihydropyridine derivatives containing the cationic pyridine moiety at the position 4, and the N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle were designed, synthesised, and assessed in biological tests. Among all the novel compounds, the 4-(N-dodecyl) pyridinium group-containing compounds 11 (without the N-propargyl group) and 12 (with the N-propargyl group) demonstrated the highest calcium antagonistic properties against neuroblastoma SH-SY5Y (IC₅₀ about 5–14 μM) and the vascular smooth muscle A7r5 cell (IC₅₀ – 0.6–0.7 μM) lines, indicating that they predominantly target the L-type calcium channels. These compounds showed a slight total antioxidant activity. At concentrations close to those of L-type calcium channel blocking ones, compound 12 did not affect mitochondrial functioning; also, no toxicity was obtained in vivo. The N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle did not essentially influence the compounds’ activity. The 4-(N-dodecyl) pyridinium moiety-containing compounds can be considered as prototype molecules for further chemical modifications and studies as cardioprotective/neuroprotective agents.