Bidentate Nucleophiles Research Articles

Bay-Substitution of Perylene Bisimides with Bidentate Nucleophiles: The Case of Aryloxide Anions.

In this study, we delve into the regioselectivity of nucleophilic reactions involving brominated perylene bisimides (PBIs) and various bidentate aryloxide anions, previously associated with an SRN1 mechanism. We present herein a new perspective, suggesting that a single-electron-transfer aromatic nucleophilic substitution (SeT-SNAr) mechanism is a more plausible scenario. Our study reveals the favorable impact of photostimulation on reaction yields, making our method a convenient approach for accessing O-arylated PBIs.

Facile Synthesis and Antioxidant Activity Screening of Some Novel 3-Substituted Indole Derivatives

The 2-cyano-3-(indol-3-yl)acryloyl chloride, a building block synthon prepared in good yield, was utilized for the synthesis of various indolylacrylamide and indole-based heterocycles. Thus, the aforementioned acid chloride was allowed to react with various oxygen, sulfur, and nitrogen nucleophiles, in addition to mono- and bidentate nucleophiles. The pyrazolidine derivatives were produced on interactions with phenylhydrazine and 2-cyanoethanohydrazide. The antioxidant activity of the synthesized compounds was assessed using the phosphomolybdenum technique and ascorbic acid as a standard. The findings displayed that indolyl-based azine, pyrazolidine, cyanoacetamide, and benzodiazepine derivatives were the most active antioxidants.

New Method for the Synthesis of Ferrocenylperfluoroalkyl 1,3-Diketones and Different Heterocycles on their Base

The Claisen condensation of acetylferrocene with perfluoroalkylcarboxylic acid esters in hexane in the presence of potassium tert-butoxide leads to the formation of potassium salts of ferrocenylperfluoroalkyl diketones. The resulting diketones are used as convenient precursors for the synthesis of various heterocyclic derivatives which have been isolated in high yields. It is shown that the [3+2]-dipolar cycloaddition with substituted azides as well as the reactions of the diketones with bidentate nucleophiles proceed regioselectively.

Synthesis and Antiproliferative Screening of Some Heterocycles Derived from 4-((5-Chloro-3-Methyl-1-Phenyl-1H-Pyrazol-4-yl)Methylene)-2-Phenyloxazol-5(4H)-One

A new series of pyrazole derivatives was synthesized starting from the pyrazole-based oxazolone derivative 3. The activity of compound 3 toward some mono- and bidentate nucleophiles was investigated. Some of the synthesized compounds were screened for their antiproliferative activity against colon and breast cancer cell lines. The results of the biological assay revealed that the triazinone derivative 13 was the most potent against the two HCT116 and MCF7 cell lines since it showed IC50 = 8.37 ± 0.5 µM and 3.81 ± 0.2 µM, respectively, as compared to the reference drug doxorubicin (IC50 = 5.23 ± 0.3 and 4.17 ± 0.2 µM, respectively).

The solvent-controlled regioselective synthesis of 3-amino-5-aryl-rhodanines as novel inhibitors of human carbonic anhydrase enzymes

The regioselective functionalization from C5-position instead of more nucleophilic NH2 of 3-NH2-Rh (1) via a green approach is representing a challenge. The primary goal of this study is to develop the solvent-promoted and -controlled regioselective bond alkylation reactions of 3-NH2-Rh (1) with NH2 free-rhodanine (1) under catalyst-free conditions. In the presence of water as the solvent, C5-addition arylation reactions of 3-NH2-Rh (1) with aldehydes efficiently gave C5-arylated-rhodanine (5-Ar-Rhs). On the other hand, using catalytic amounts of an acid catalyst in ethanol, the reaction of 3-NH2-Rh (1) and aldehydes resulted in the arylation of rhodanine at the NH-position. Water plays two roles in the reactions: converting the 3-NH2-Rh (1) into bidentate nucleophiles and activating the C-5 position of 3-NH2-Rh (1) to achieve the Knoevenagel condensation via hydrogen bond clusters. The 3-NH2-Rh (1) act as a C-nucleophile due to the H-bond clusters between water and the amino group of 3-NH2-Rh (1), whereas upon using catalytic amounts of CH3CO2H in pure ethanol the compounds act as an NH2-nucleophile. Moreover, the enzyme inhibition studies of novel 5-Ar-Rhs against cytosolic carbonic anhydrase (hCAs) I, and II isoforms was carried out. As a result of these biological studies, inhibition constants (Ki) for hCA I and hCA II were found in the range of 239.88 ± 79.31 to 610.24 ± 111.43 nM, and 262.69 ± 13.20 to 638.10 ± 127.73 nM, respectively.

Synthesis of 4‐Hydroxy‐2‐pyridinone Derivatives and Evaluation of Their Antioxidant/Anticancer Activities

AbstractA simple approach was applied for the regioselective synthesis of various pyridine‐2‐one derivatives or annulated pyridine as novel heterocyclic systems from the reaction of dehydroacetic acid (DHA) with mono‐ or bidentate nucleophile as with benzylamine and/or phenylenediamines in dichloromethane followed by transformation with different halo‐compounds in refluxing 1,4‐dioxane has been achieved in moderate to excellent yields (48‐93 %). In addition, DFT studies of the key synthesized compounds were carried out for confirmed proposed mechanisms. The newly synthesized compounds were screened for their in‐vitro inhibition activities against mammary gland breast cancer (MCF‐7) and human prostate cancer (PC‐3) using the MTT colorimetric method. Also, the target synthesized compounds were evaluated as antioxidant agents.

Acryloyl isothiocyanate skeleton as a precursor for synthesis of some novel pyrimidine, triazole, triazepine, thiadiazolopyrimidine and acylthiourea derivatives as antioxidant agents

ABSTRACT The reactions of 2-cyano-3-pyrazolylpropenoyl isothiocyanate derivative 2 with some mono- and bidentate nucleophiles namely, dodecan-1-amine, 6-aminothiouracil, hydrazine, phenylhydrazine, phenylurea, semicarbazide, and thiosemicarbazide, in addition to some derivatives of hydrazides, have been investigated to obtain some valuable heterocyclic skeletons gathering with a pyrazole core, viz. pyrimidine, triazole, triazepine, thiadiazolopyrimidine as well as acylthiourea derivatives. Hydrazinolysis of 2 was found to provide a mixture of thiosemicarbazide, diheterylazine, and triazepine derivatives. Treatment of 2 with phenylhydrazine was mainly dependent on the reaction conditions to produce a mixture of pyrimidinethione and triazole derivatives at room temperature or the triazepine derivative at heating conditions. The antioxidant activity screening of these compounds disclosed that pyrimidinethione derivatives 9 and 13 exhibited the most potency.

Development of Chromone–Pyrazole-Based Anticancer Agents

Chemical reactivity of 4-((6-chloro-4-oxo-4H-chromen-3-yl)methylene)-2-phenyloxazol-5(4H)-one towards nitrogen and sulfur nucleophiles, as well as bidentate nucleophiles, has been studied under various conditions. The investigated nucleophilic reactions result in formation of heterocyclic systems, namely pyrazolyloxazolone, pyrazoldihydrotriazinone, chromonylimidazolone, chromonylimidazol, and chromonylbenzo[d]imidazole and chromonyloxathiazepine derivatives. All the synthesized products were screened for their anticancer activity against two cell lines, namely human colon (HCT-116) and mammary gland breast cancer (MCF-7) using the MTT assay. Some of the investigated compounds showed remarkable cytotoxic activities against HCT-116 (IC50 7.74‒82.49 µg/mL) and MCF-7 (IC50 4.98‒92.62 µg/mL) cells in comparison to the standard anticancer drug doxorubicin (IC50 5.23 and 4.17 µg/mL, respectively). Among the tested compounds, pyrazolbenzamide and pyrazoldihydrotriazinone derivatives were the most significant antiproliferative efficacy against the two cell lines. Our findings suggest that the designed compounds may be considered promising antiproliferative agents.

Synthesis of Emissive Heteroacene Derivatives via Nucleophilic Aromatic Substitution.

A synthetic approach for preparing a variety of heterocyclic tetrahydropentacene derivatives via nucleophilic aromatic substitution reactions of bidentate nucleophiles and tetrafluoroterephthalonitrile was developed. X-ray crystallography of several products revealed that the compounds containing oxygen and nitrogen heteroatoms are highly planar and engage in π-stacking, while the compounds containing sulfur are bent and do not stack as effectively. The compounds were also highly emissive, and the heteroatom had a significant impact on the emission and electrochemical properties.

Understanding the Reactivity of Group 6 Metal (M = Cr, W) Alkynyl Fischer Carbene Complexes with Multi‐Reactive Masked Dienes

Group 6 alkynyl Fischer carbene complexes behave as electrophiles with highly reactive masked dienes such as anthrone and 3‐hydroxy‐2‐pyrone, which also can react as bidentate nucleophiles. Both Cr0 and W0 alkynyl carbene complexes require tertiary amines to promote the formation of 1,4‐C‐addition products, but a marked dependence of the reactivity on the metal was observed. Although W0 complexes form exclusively the 1,4‐C‐adducts in the presence of a catalytic amount of base, Cr0 complexes lead to new anthrone‐derived bis‐carbene complexes, obtained by a sequential 1,4‐C‐ and 1,4‐O‐addition process with high diastereoselectivity and only in the presence of an excess of base. DFT computational studies show that the gap between the LUMO of the complex and the HOMO of the anthrone determines the differences in reactivity and that the stability of the intermediate metal allenyls formed after the initial 1,4‐addition is decisive for the outcome of the reaction.

ChemInform Abstract: Synthesis of New α‐Trifluoromethyl Substituted Formamidines Framework by Using N‐Nucleophiles and N,S Bidentate Nucleophiles.

Abstract An efficient and convenient method for the preparation of new trifluoromethylated benzimidazole, imidazole and benzothiazole derivatives in excellent yields via reaction of N -aryl-2,2,2-trifluoroacetimidoyl chlorides with benzimidazole or benzothiazole or imidazole derivatives in the presence of NaH or NEt 3 as a base in acetonitrile or THF without assistance of any catalyst has been reported. Also nucleophilic substitution of N -aryl-2,2,2-trifluoroacetimidoyl chlorides with unequal N and S bidentate nucleophiles occurred at N position. The FT-IR, 19 F NMR, 1 H NMR, 13 C NMR, UV spectra and elemental analysis confirm the structures of the products.

Synthesis of new α-trifluoromethyl substituted formamidines framework by using N-nucleophiles and N,S bidentate nucleophiles

An efficient and convenient method for the preparation of new trifluoromethylated benzimidazole, imidazole and benzothiazole derivatives in excellent yields via reaction of N-aryl-2,2,2-trifluoroacetimidoyl chlorides with benzimidazole or benzothiazole or imidazole derivatives in the presence of NaH or NEt3 as a base in acetonitrile or THF without assistance of any catalyst has been reported. Also nucleophilic substitution of N-aryl-2,2,2-trifluoroacetimidoyl chlorides with unequal N and S bidentate nucleophiles occurred at N position. The FT-IR, 19F NMR, 1H NMR, 13C NMR, UV spectra and elemental analysis confirm the structures of the products.

Organocatalyst-Induced Multicomponent Reaction: An Efficient Procedure for the Activation of Amides

An efficient organocatalytic route for the activation of amide derivatives is reported. In this transformation, amide derivatives were employed as a potential bidentate nucleophile in a reaction involving isoquinoline and propiolates using tetrabutylphosphonium acetate to form 1,2-dihydroisoquinoline skeletons.

Regiochemistry of nucleophilic substitution of pentachloropyridine with N and O bidentate nucleophiles

Anions derived from N-aryl formamides can be attacked to 4-position of pentachloropyridine via N or O site base on electron-withdrawing or electron-releasing groups attached to phenyl ring.

Dimethyl Carbonate as a Sacrificial Molecule for the Synthesis of 5‐Memebered N‐ and O‐Heterocycles

AbstractIn the last twenty years DMC has been employed as an efficient methylating and methoxycarbonylating agent with several monodentate and bidentate nucleophiles, showing great selectivity and unexpected results. In this short review we report on yet another application of DMC chemistry i.e. the synthesis of 5‐membered N‐ and O‐heterocycles. In these reactions DMC acts as a sacrificial molecule since it is not present in the final products, but only in the reaction intermediates as an halogen‐free leaving group. This DMC‐based synthesis of heterocycles resulted of general application, as it is effective for aliphatic and aromatic 1,4‐diols, incorporating several functionalities (primary, secondary, tertiary, allylic, phenolic), as well as, for bifunctional compounds i.e. 4‐amino‐1‐butanol. This synthetic procedure was also employed for industrially relevant compounds such as (‐)‐norlabdane oxide and isosorbide showing to maintain the chiral integrity of the substrate. In one case intramolecular cyclisation of isosorbide was also observed to achieve a strained tricyclic derivative. Comparing this reaction methodology with a chlorine based procedure, the DMC‐mediated pathway is quantitative, occurs in one step, does not require any chlorine‐based chemical or strong acid and does not produce any chlorinated waste material.

Synthesis, antimicrobial and DNA cleavage studies of some 4-aryloxymethylcoumarins obtained by reaction of 4-bromomethylcoumarins with bidentate nucleophiles

Symmetrical bidentate nucleophiles such as resorcinol have been made to react with 4-bromomethylcoumarins in a cascaded manner to obtain mono and bis-4-aryloxymethylcoumarins by a room temperature allylic nucleophilic displacement. Unsymmetrical nucleophiles such as 3-acetylaminophenol and 3-diethylaminophenol have been used to generate 4-aryloxymethylcoumarins. All the compounds have been analyzed by spectral methods and subjected to preliminary antibacterial, antifungal and DNA cleavage studies. The results showed that the compounds bearing methoxy, chloro and bromo substituents at C6-position of coumarin showed higher activity. Symmetrical bidentate nucleophiles such as resorcinol, and unsymmetrical nucleophiles, 3-acetylaminophenol and 3-diethylaminophenol have been made to react with 4-bromomethylcoumarins in a cascaded manner to obtain corresponding 4-aryloxymethylcoumarins. All the compounds have been analyzed by spectral methods and subjected to preliminary antibacterial, antifungal and DNA cleavage studies.

Electrochemical synthesis of novel π-extended phenoxazine derivatives of porphyrincatecholes

Three new functionalized phenoxazine-catechol porphyrins 7a–c have been synthesized by a green one-pot method and structurally characterized by spectroscopic analysis. The electro-oxidation of 5,10,15,20-tetrakis(2,3-dihydroxyphenyl) porphyrins( 1a–c) with four catechol units in the presence of 2-aminophenol 8 as bidentate nucleophile has been done and phenoxazine rings have been formed by intermolecular and intramolecular Michael addition reactions. Spectroscopic characterization and voltammetry results have allowed us to propose four independent ECEC mechanisms for the electrochemical oxidation pathway. The functionalization of the porphyrins affected their photophysical properties. Expansion of the UV–vis spectrum range and the decrease of the fluorescence intensity of the products would support the energy transfer between the porphyrin core excited states to the four substitutions as the electron acceptor subunits. SEM images indicate that this method produces regularly shaped manganese porphyrin nano-particles 7c that possess a cubic nano structure.

Utility of 2-cyano-3-phenyl-2-propenoyl chloride as Michael’s acceptor in heterocyclic synthesis with mono- and bi-dentate nucleophiles

( E ) 2-Cyano-3-phenyl-2-propenoyl chloride reacts with nitrogen, oxygen and sulphur mono- and bi-dentate nucleophilic reagents to give the amide derivatives, the ester derivatives, as well as some heterocyclic systems, namely quinazolinone, pyridopyrimidine and benzothiazepine. Cyclization of some obtained amides affords the benzoxazinones, quinazolinone, whereas that of other amides yields oxadiazole and benzoxazole, respectively.

A promising green method in cyclization reaction. Oxidation of 3-methylcatechol in the presence of 1,10-phenanthroline

Abstract Electrochemical oxidation of 3-methylcatechol as a model compound has been studied in the presence of 1,10-phenanthroline as a bi-dentate nucleophile in water/acetonitrile (70/30, v/v) solution using cyclic voltammetry and controlled-potential coulometry. The results revealed that anodically generated 3-methylcyclohexa-3,5-diene-1,2-dione participates in inter and intramolecular Michael addition reactions with 1,10-phenanthroline and via an ECEC pathway converts to the corresponding heterocyclic compound. The present work has led to the development of a facile and one-pot method with high atom economy under ambient conditions and in an undivided cell using a carbon electrode.

Electrosynthesis of novel π-extended benzofuran derivatives of porphyrincatecholes

Two new functionalized π-extended benzofuran catechol porphyrins and nanostructured Mn-porphyrins have been synthesized by a green one-pot method and structurally characterized by spectroscopic analysis. The electro-oxidation of 5,10,15,20-tetrakis(2,3-dihydroxyphenyl) porphyrins( 1a-b) with four catechol units in the presence of 3-hydroxy-1H-phenalene-1-one ( 3) as bidentate nucleophile has been done and benzofuran rings have formed by the intermolecular and intramolecular Michel addition reactions. Coulometry and voltammetry results allowed us to propose four independent ECEC mechanisms for the electrochemical oxidation pathway. Functionalization of the porphyrins affected their photophysical properties such as the efficiency of the fluorescence that would support the energy transfer between the porphyrin core and the substituted subunits.