Meerwein Arylation Reaction Research Articles

Meerwein Arylation of Aryl(alkyl)idenemalononitriles and Diazonium Salts for the Synthesis of 2-(Aryl(alkyl)/arylmethylene)malononitrile Derivatives.

A metal-free Meerwein arylation reaction from aryl(alkyl)idenemalononitriles and diazonium salts for the synthesis of 2-(aryl(alkyl)/arylmethylene)malononitrile derivatives under mild conditions was well developed. Different from the general addition reactions between alkenes and diazonium salts, this study performed the traditional coupling reaction for the formation of C(sp2)-C(sp2) bond arylation products. The radical reaction mechanism was well verified in the control experiments. The other advantages of the approach are broad-scope substrates and good group tolerance. Moreover, the obtained products can be readily converted into high-value asymmetric ketones and hydrogenation reactions.

Preparation and properties of a novel fluorinated epoxy resin/DGEBA blend for application in electronic materials

A novel epoxy monomer 4-trifluoromethyl phenylhydroquinone epoxy resin (4-TFMEP) was synthesized via a multistep procedure including the Meerwein arylation reaction and followed by nucleophilic reaction. The chemical structure of 4-TFMEP was confirmed by proton nuclear magnetic resonance and Fourier-transform infrared spectrum. Then a mixed system (DGEBA/4-TFMEP x%) composed of diglycidyl ether of bisphenol A (DGEBA) and 4-TFMEP was prepared by a melting method without any solvent. After curing, the properties of this series of mixed epoxy resins were measured and compared with the neat DGEBA. As a result, the blend resins exhibited good thermal stability, excellent hydrophobic and low dielectric properties with 4-TFMEP content increasing. Furthermore, the material of DGEBA/4-TFMEP 40% achieves higher glass transition temperature of 104°C and char yield 33% than DGEBA (char yield = 22%) possessed. In the contact angle testing, DGEBA/4-TFMEP 40% shows 127.2° satisfied the standard of hydrophobic material. In addition, by the test of dielectric properties, DGEBA/4-TFMEP x% materials show lower than DGEBA/boron trifluoride ethylamine (BF3MEA) material, because of the introduced side group of fluorine content into the material improves the electronegativity of epoxy material and reduced the polarizability of molecules efficient. Herein, we believe the novel mixed epoxy system (DGEBA/4-TFMEP x%) has a potential application in electronic industries.

Study of the reaction of iodoarylation of phenylacetylene by benzenediazonium tetrafluoroborate

Anion-arylation reaction, as well as its partial case – Meerwein arylation reaction, is a valuable tool for construction of practically important compounds. Such reactions are mainly catalyzed by transition metals. In the same time, iodo-arylation is self-catalyzed reaction and does not require utilization of eco-unfriendly heavy-metal containing catalysts. However, there are only several reports concerning to this topic. In order to shed more light on the nature and distributions of products of this reaction, herein we thoroughly investigated iodoarylation reaction of phenylacetylene by benezenediazonium tetrafluoroborate in the presence of lithium iodide. Reaction has been performed at 0‑5°C in DMF. For analysis of reaction products and its ratio GC‑MS analysis have been applied. Seven main products of this reaction have been found. In the reaction mixture typical product of Sandmeyer reaction – iodobenzene (33.9 %) has been identified. Although in course of the reaction formation of dimethylaminobenzene (6.5 %) take place. Probably, formation of last is a result of benzene radical attack on the solvent (DMF). In the same time, formation of diiodostyrene (10.2 %) in reaction mixture was predictable, because it is well known that iodine anion easily can be oxidized by arenediazonium salts to elemental iodine, which further reacts with starting phenylacetylene. Further, orto- and para-iodobiphenyls (8.7 and 4.1 %, respectively) have been identified in the reaction mixture. Formation of such products was unexpected, however can be explained as subsequent arylation by Gomberg-Bachmann-Hey type reaction of formed iodobenzene. Finally, desired E- and Z-iodostilbenes have been formed in 36.6 % total yield with E/Z ratio close to 3:1. In conclusion, products of iodo-mediated reaction of benzenediazonium tetrafluoroborate with phenylacetylene in presence of lithium iodide have been investigated by GC‑MS analysis. Possible ways of formation of all identified compounds have been suggested. Key words : iodo-arylation, iodostilbenes, arenenediazonium salts, phenylacetylene, chromato-mass spectrometry.

Arylnaphthoquinones. 8. Synthesis of 6-arylbenzo[a]phenazines

Quinonoid compounds widespread in wildlife are involved in many biological processes and are extremely important for almost every living organism. On the other hand, the features of the structure of quinones cause a wide range of their chemical transformations. They are active in many homolytic and heterolytic reactions capable of cycloaddition. A practically important group of reactions leading to the formation of heterocyclic compounds with nitrogen atoms in the cycle is the interaction between benzo- and naphthoquinones and aliphatic and aromatic diamines as well as their derivatives. However, among the condensed nitrogen-containing heterocycles there were found practically useful substances for which anticancer, antiparasitic, antimicrobial and other biological activities were recorded. For example, the main representatives of the group of arylamine dyes are derivatives of phenazine, phenothiazine and phenoxazine. Phenazines are also widely used in the field of organic electronics, in particular, they are integrated into solar cells and OLED devices. Possibility of preparation of angular heterocyclic systems based on 3-aryl-1,2-naphtho-quinones were investigated. The 3-aryl-1,2-naphthoquinones 1–6 (аryl = 4-ClC 6 H 4 (1), 4-BrC 6 H 4 (2), 3-NO 2 C 6 H 4 (3), 4-NO 2 C 6 H 4 (4), 2,5-Cl 2 C 6 H 3 (5), 3,4-Cl 2 C 6 H 3 (6)) were obtained by means of the reaction between arenediazonium salts and 1,2-naphthoquinone under Meerwein reactions conditions. The reactions were carried out in formic acid – water medium in the presence of sodium acetate and catalytic amounts of copper salts. The yields of arylnaphthoquinones 1–6 are in range of 20–50 %. The reaction of 3-aryl-1,2-naphthoquinones 1–6 with benzene-1,2-diamine led to the formation of fused angular heterocyclic systems of 6-arylbenzo[ a ]phenazines 7–12 in high yields. The structures of the synthesized compounds were verified by the 1 H NMR spectroscopy and element analysis data. Key words: 1,2-naphthoquinone, benzene-1,2-diamine, 3-aryl-1,2-naphthoquinones, Meerwein arylation reaction, benzo[ a ]phenazines.

Iron powder and tin/tin chloride as new reducing agents of Meerwein arylation reaction with unexpected recycling to anilines

Simple and rapid route for Meerwein arylation reaction using iron powder or a mixture of tin/tin chloride has been developed. In the presence of iron powder, different aryl diazonium salts reacted with methyl vinyl ketone, acrylates, and isopropenyl acetate. Production of oximes was detected as the main product with acrylates or in a mixture with β-aryl methyl ketones in the case of methyl vinyl ketone. The in situ produced HNO2 from an excess of NaNO2/HCl was trapped by alkyl aryl radical to form oximes in the E configuration form. The presence of tin/tin chloride mixture in the reaction of the aryl diazonium salts with methyl vinyl ketone produced Michael products along with β-aryl methyl ketones. The predicted α-aryl methyl ketones from the reaction of isopropenyl acetate with the diazotized anilines were obtained using iron or tin/tin chloride mixture.

Estrogenic activity research of a novel fluorinated bisphenol and preparation of an epoxy resin as alternative to bisphenol A epoxy resin

A low estrogenic activity bisphenol 3,5-bis(trifluoromethyl)phenylhydroquinone (BTFMHQ) and its corresponding epoxy resin (BTFMEP) were synthesized via a multi-step procedure including the Meerwein arylation reaction, and followed by nucleophilic reaction. The chemical structures of two monomers were confirmed by their 1H NMR spectra. After curing, the properties of this fluorinated epoxy resin were measured and compared with the commercial epoxy resin diglycidyl ether of bisphenol A (DGEBA). As the result, BTFMEP exhibited good dimensional stability, excellent hydrophobic and low dielectric properties. Furthermore, BTFMEP showed a high glass transition temperature of 142 °C and a lower coefficient thermal expansion (CTE = 55.03 ppm/°C) than that of DGEBA (CTE = 60.71 ppm/°C). Moreover, BTFMEP exhibited the contact angle of 99.6°, which satisfied the standard of hydrophobic material. In addition, BTFMEP showed lower dielectric properties than DGEBA, because the introduction of side groups with high fluorine content into the material improved the electronegativity of epoxy material and reduced the polarizability of molecules efficiently. Herein, we believe the novel epoxy resin (BTFMEP) has a wide application prospect as the alternative to DGEBA.

Facile synthetic route to benzo[c]chromenones and thieno[2,3-c]chromenones

ABSTRACTConvenient two-step procedure for the synthesis of fused chromenone derivatives was developed. Reduction of the obtained in the Meerwein arylation reaction aryl- and thienylquinones allowed to construct 6H-benzo[c]chromene-6-ones and 4H-thieno[2,3-c]chromen-4-one in a more cost- and time-effective manner in comparison with already known methods. The obtained products have provided a new entry to chromenone derivatives.

Synthesis and Larvicidal Activity of Novel Thenoylhydrazide Derivatives.

A pair of chemical isomeric structures of novel N-tert-butylphenyl thenoylhydrazide compounds I and II were designed and synthesized. Their structures were characterized by MS, IR, 1H NMR, elemental analysis and X-ray single crystal diffraction. The regioselectivity of the Meerwein arylation reaction and the electrophilic substitution reaction of N-tert-butyl hydrazine were studied by density functional theory (DFT) quantum chemical method. The larvicidal tests revealed that some compounds I had excellent larvicidal activity against Culex pipiens pallens. As the candidates of insect growth regulators (IGRs), the larval growth inhibition and regulation against Culex pipiens pallens were examined for some compounds, especially I1 and I7. Compounds I1 and I7 were further indicated as an ecdysteroid agonist by reporter gene assay on the Spodoptera frugiperda cell line (Sf9 cells). Finally, a molecular docking study of compound I7 was conducted, which was not only beneficial to understand the structure-activity relationship, but also useful for development of new IGRs for the control of mosquitos.

Practical, Highly Convergent, Asymmetric Synthesis of a Selective PPARγ Modulator

A practical, highly convergent, asymmetric synthesis of a selective PPARγ modulator 1 is described. The inhibitor contains two key components, a 6-trifluoromethoxy-3-acylindole (6) and (R)-α-aryloxybutanoic acid derivative (10). Two methods were developed to overcome the regioselectivity issues encountered in the preparation of the 6-substituted indole. The first involved an intramolecular Heck reaction of an iodoaryl enamine. The second involved application of a catalytic Meerwein arylation reaction between 2-nitro-4-trifluoromethoxyaniline and isopropenyl acetate and subsequent reductive cyclization. The α-aryloxybutanoic acid was prepared via an asymmetric hydrogenation of the corresponding α-aryloxy-α,β-unsaturated acid. Tetrabutylammonium iodide-catalyzed coupling of the two fragments and ester hydrolysis completed the convergent synthesis. The described convergent synthesis was used to prepare >3 kg of drug substance 1 in 50% overall yield and with >99.5% ee.

Synthesis of 1-aryl-2-propanones

A new convenient synthesis of a series of 1-aryl-2-propanones using aromatic amines as precursors, via diazo-reaction and improved Meerwein arylation reaction under mild conditions, was achieved. In addition, 1-[3,5-bis(trifluoromethyl)phenyl]-2-propanone is a new compound among the synthesized compounds. This approach is an efficient synthetic method for the aryl-propanones with different substituting groups.

Facile Synthesis of 1‐Aryl‐2‐propanones from Aromatic Amine

A facile synthesis of aryl propanones using aromatic amines as precursors, via an improved Meerwein arylation reaction under mild conditions, is reported.

Synthese von 1,7‐Diazaperylen

Synthesis of 1.7-Diazaperylene The hitherto unknown 1,7-Diazaperylene (2) has been prepared in a five-step synthesis from 1,5-diaminoanthraquinone (3) by a Meerwein arylation reaction. Applications as a fluorescent dye are discussed.

Synthesis of the glivocarcin-M aglycone

The synthesis of the agylcone of the antibiotic Gilvocardin-M by a sequential Meerwein Diels-Alder route is reported. The D-ring of the agylcone is attached by a halogen atom directed Meerwein arylation reaction and the A-ring is attached by a halogen atom directed Diels-Alder reaction. In the key step the directing chlorine atom is removed by a new thiophenylation reduction sequence.

Synthesis and class III antiarrhythmic activity of (phenylbut-2-enyl)ammonium salts. Effect of conformation on activity.

The syntheses of seven 4-(substituted phenyl)but-2-en(or yn)yl quaternary ammonium salts and four related tertiary amines are described. The Meerwein arylation reaction was the preferred synthetic method for the required intermediate 1-aryl-4-halo-2-butenes (15a-c, 18). In the case of 18, the trans stereochemistry of the Meerwein adduct of 2,3-dimethylbutadiene was established unambiguously by 2D NMR and X-ray studies. The title compounds represent conformationally restricted analogues of the class III antiarrhythmic agent clofilium (1) and exhibit comparable potency and efficacy in the in vitro evaluation using isolated canine Purkinje fibers. These results suggest that the alkylene chain in 1 is extended in the active conformation. Computer-aided conformational analysis (MM2) supports this conclusion. Selective catalytic hydrogen conditions were developed for the conversion of the unsaturated analogue 2 to clofilium (1) with minimal hydrogenolysis of the allylic quaternary ammonium moiety, thus completing a novel and efficient synthesis of this substance.

Diels–Alder dimerization of 2-arylmaleimides. X-Ray crystal structure of the dimer of 2-p-tolylmaleimide

Dimers (4) and (7) were obtained during the course of the Meerwein arylation reaction; a Diels–Alder reaction is proposed for the mechanism of the dimerization, and the X-ray structure of (4) is reported.

Alkyl nitrite-metal halide deamination reactions. 3. Arylation of olefinic compounds in the deamination of arylamines by alkyl nitrites and copper(II) halides. A convenient and effective variation of the Meerwein arylation reaction

Alkyl nitrite-metal halide deamination reactions. 3. Arylation of olefinic compounds in the deamination of arylamines by alkyl nitrites and copper(II) halides. A convenient and effective variation of the Meerwein arylation reaction