•A safe and convenient decarboxylative nitration method for cinnamic acids.•Chlorotrimethylsilane-Cu(NO3)2·3H2O is an efficient nitrating system.•Decarboxylative nitration is stereoselective.•Bromotrimethylsilane-Cu(NO3)2·3H2O is an efficient brominating system.•The nitration and bromination methods are versatile for a variety of cinnamic acids.Further synthetic potential of halotrimethylsilane-nitrate salt mixture is revealed. A mixture of TMSX-Cu(NO3)2·3H2O system is found to be an efficient reagent system for both the decarboxylative nitration (ipso-nitration) when X = Cl, and dibromination of cinnamic acids, with X = Br, under mild conditions. The reactions are safe and simple, affording the corresponding products (E)-β-nitrostyrenes, and anti-2,3-dibromo-3-phenylpropanoic acids in high yields with high selectivity in a relatively short time. Use of hazardous and toxic nitrating systems such as acetyl nitrate and brominating agents such as molecular bromine can be avoided.Download high-res image (55KB)Download full-size image

•Direct one-pot synthesis of 2-/3-(trifluoromethyl)thiochroman-4-ones is achieved.•2-/3-(Trifluoromethyl)acrylic acid is used as an effective CF3 motif.•Reaction occurs by superacid induced tandem S-alkylation-cyclic acylation.•A reactive superelectrophilic dicationic species is proposed as the key intermediate.Incorporation of fluorinated heterocyclic framework into organic molecules results in profound changes in their physical, chemical and biological properties. Realizing that the fluorinated thiochroman-4-ones are important scaffolds in medicinal chemistry and are rare in the chemical literature, one-pot synthesis of 2-/3-(trifluoromethyl)thiochroman-4-ones was attempted. Direct access to 2-/3-(trifluoromethyl)thiochroman-4-ones was achieved by a tandem alkylation-cyclic acylation process promoted by superelectrophilic activation of 2-/3-(trifluoromethyl)acrylic acid in superacidic trifluoromethanesulfonic acid under microwave-assisted Friedel-Crafts alkylation of benzenethiols followed by cyclization (via intramolecular acylation). Synthesis of a series of 2-/3-(trifluoromethyl)thiochroman-4-ones from protosolvated 2-/3-(trifluoromethyl)acrylic acid intermediates and benzenethiols is described.Download high-res image (71KB)Download full-size imageDirect one-pot synthesis of 2-/3-(trifluoromethyl)thiochroman-4-ones is achieved by a superacid induced tandem S-alkylation-cyclic acylation.

Benzodiazines (diazonaphthalenes with both nitrogens in the same ring) – cinnolines (1,2-benzodiazine), quinazolines (1,3-benzodiazine), phthalazines (2,3-benzodiazine) and quinoxalines (1,4-benzodiazine) – are important class of compounds with broad biological properties and wide application in pharmaceutical as well as agrochemical arenas. These diazaheterocycles are present in a wide variety of bioactive natural products as well as synthetic molecules that are good drug candidates constituting key structural units responsible for their pronounced therapeutic activities. Their rapidly growing uses and applications in medicinal and agrochemical arenas prompt the researchers for further studies on this important group of compounds. In this review, we hope to provide a brief overview of the important general methodologies and recent developments towards their synthesis and open the door for further progress in this area.

Boron trifluoride monohydrate is an excellent Brønsted acid catalyst system for a wide range of reactions. It is a non-oxidizing acid catalyst prepared easily by bubbling BF3 into water. We have found boron trifluoride monohydrate/sodium azide combination to be an efficient reagent system for aromatic electrophilic amination. The present method avoids the use of expensive superacids such as trifluoromethanesulfonic acid and provides a facile access to aromatic amines directly from aromatics.

Friedel–Crafts type aromatic nitration has served as an indispensable reaction within both industrial and academic applications. However, growing concern over the use of copious amounts of strong acids has prompted the search for more environmentally friendly alternatives. Polymer-bound Brønsted acids, on the other hand, have been shown useful as convenient alternatives to liquid acids. Nitric acid and sulfuric acids have, therefore, been combined, both individually and as a mixture, with poly(4-vinylpyridine). The new solid acid systems have been used to nitrate both activated and deactivated arenes under mild conditions and proved to be effective nitrating agent.

An efficient microwave-assisted protocol for the synthesis of 2-/3-methylthiochroman-4-ones by superacid-catalyzed alkylation followed by cyclic acylation (cyclization via intramolecular acylation) is described. Using easily accessible benzenethiols and crotonic acid/methacrylic acid with triflic acid (as catalyst of choice for needed optimal acidity), the reaction was tuned toward the formation of the cyclized products in good selectivity and yield. A mechanism involving the formation of carbenium–carboxonium superelectrophilic species is suggested.

•Poly(4-vinylpyridine)-triflic acid complex, a solid triflic acid equivalent was prepared.•Friedel–Crafts hydroxyalkylation and acetylation of arenes were investigated.•Facile synthesis of diary acetic acid derivatives in high yields was achieved.The application of poly(4-vinylpyridine) supported trifluoromethanesulfonic acid (PVP-TfOH, 1:10) as a convenient solid superacid catalyst system in Friedel–Crafts reactions is described. In the presence of PVP-TfOH, one pot solvent-free synthesis of a wide variety of diarylacetic acid derivatives was achieved by Friedel–Crafts hydroxyalkylation reaction of glyoxylic acid with arenes under mild conditions. Acylation of both activated and deactivated aromatic compounds with acetyl chloride was also achieved using PVP-TfOH complex under solvent-free conditions at room temperature. As the polymer supported triflic acid was found to be a very efficient and an easy-to-handle solid acid, it can be a useful addition to environmentally more adaptable strong acid catalyst systems.PVP-TfOH, prepared from poly(4-vinylpyridine) and triflic acid, acts as a covenient solid equivalent of triflic acid and used efficiently as superacid catalyst in the Friedel–Crafts hydroxyalkylation and acetylation of arenes as well as Fries rearrangement. Direct synthesis of a wide variety of diarylacetic acid derivatives was achieved by the hydroxyalkylation of arenes with glyoxylic acid under mild conditions.

Complexes of poly(N-vinylpyrrolidone) (PVD) and poly(4-vinylpyridine) (PVP) with hydrogen peroxide have been prepared and their synthetic utility as solid H2O2 equivalents for the selective oxidation of sulfides to sulfoxides and ketones to gem-dihydroperoxides has been studied. These complexes are convenient and safe alternatives to H2O2 solutions and it is found that various symmetric as well as unsymmetrical sulfides undergo oxidation under mild conditions to provide the respective sulfoxides in high yields. A series of gem-dihydroperoxides were obtained from the corresponding ketones in good yields under ambient conditions.

Nitroso compounds are versatile reagents in synthetic organic chemistry. Herein, we disclose a feasible protocol for the ipso-nitrosation of aryl boronic acids using chlorotrimethylsilane–sodium nitrite unison as nitrosation reagent system.

Biginelli reaction is the most well-known and widely studied multicomponent reaction used for the direct synthesis of many biologically active 3,4-dihydropyrimidinones or thiones and their derivatives by reacting a β-keto ester/1,3-dicarbonyl compound, an aldehyde, and urea/thiourea. A new easily recoverable solid catalyst, Nafion-Ga (Gallium Nafionate, Ga(III) salt of Nafion-H, a solid polymeric perfluoroalkanesulfonic acid) was prepared from Nafion-K by metal exchange. Nafion-Ga is found to be an efficient and environmentally benign catalyst for the Biginelli reaction. A series of 3,4-dihydropyrimidinones and thiones were conveniently prepared by this green protocol using the catalyst under solvent free conditions. The wide scope of the catalyst for many other acid catalyzed organic transformations can be ascertained by further screening studies.

The synthesis of various α-aminonitriles, precursors of α-amino acids has been carried out in moderate to high yields and high purity by the Strecker reaction from ketones, aliphatic/aromatic amines and TMSCN using a new “green” Lewis acid catalyst, Nafion–Fe (iron Nafionate, Fe(III) salt of Nafion–H, a solid polymeric perfluoroalkanesulfonic acid) under conventional thermal as well as microwave conditions. Microwave and solvent-free conditions applied in this method shorten the reaction times, improve the yields and diminishes the formation of side products. Strecker reaction occurs smoothly with secondary aliphatic amines also under these conditions which is not common under conventional conditions.

A palladium-catalyzed allylation reaction of PhSO2CH2CF3 (2) with a variety of allyl carbonates has been successfully developed for selective 2,2,2-trifluoroethylation under neutral conditions. With this method, the 1-phenylsulfonyl-2,2,2-trifluoroethyl moiety was efficiently transferred into organic compounds without the competing β-elimination of fluoride, to afford a range of mono-allylated and di-allylated compounds.

Superacid catalyzed electrophilic substitution of arenes using 4,4,4,-trifluoro/3-trifluoromethylcrotonic acids has been investigated. The direct synthesis of various trifluoromethylated dihydrochalcones, aryl vinyl ketones and indanones has been achieved by this methodology. It has been found that the position of the trifluoromethyl group has a profound effect on the nature of the reaction and the products. In the pharmaceutical industry, many fluoroorganics are shown to possess significant biological and therapeutic activities. Therefore, these novel compounds can be considered key intermediates for the preparation of potential biologically active molecules.Graphical abstractDirect synthesis of trifluoromethylated dihydrochalcones, aryl vinyl ketones, and indanones has been achieved by superelectrophilic activation of 4,4,4-trifluoro/3-(trifluoromethyl)crotonic acids followed by Friedel–Crafts alkylation/acylation/cyclalkylation in excess triflic acid.Highlights► Superacid catalyzed electrophilic substitution of arenes using 4,4,4,-trifluoro/3-trifluoromethylcrotonic acids has been investigated. ► Synthesis of various trifluoromethylated dihydrochalcones, aryl vinyl ketones and indanones has been achieved. ► Position of the trifluoromethyl group seems to have profound effect on the nature of the reaction and the products. ► Mechanistic aspects have been supported by ab initio calculations.

Nafion-H and Nafion SAC-13 are efficient solid Brønsted acid catalysts for the preparation of trifluoromethyl ketimines from benzylamines and trifluoromethylated ketones in high yields. A finely tuned benzylimine–benzaldimine rearrangement by facile 1,3-hydrogen shift has been achieved for the formation of fluorinated benzaldimines in high yields by careful optimization of reaction conditions including attempts under microwave conditions and a flow system. These α-trifluoromethylated benzaldimines are efficient precursors for pharmaceutically important α-trifluoromethylated benzylamines, accessed through their direct acid hydrolysis.

A mixture of chloro/bromotrimethylsilane and nitrate salt is found to be an effective reagent system for the α-chlorination/bromination of carbonyl compounds. The reaction occurs under mild conditions yielding the products in moderate to good yields.

Direct hydroamination of aldehydes and ketones provides one-step entry into desired α-aminoalkane derivatives which are important synthons for many biologically active molecules. The reductive amination of aldehydes in the presence of silanes has been effectively promoted by Ga(OTf)3 as a catalyst. Mild conditions, easy work-up and high purity of products with excellent yields are the major advantages of this method.

Benzodiazines (diazonaphthalenes with both nitrogens in the same ring) – cinnolines (1,2-benzodiazine), quinazolines (1,3-benzodiazine), phthalazines (2,3-benzodiazine) and quinoxalines (1,4-benzodiazine) – are important class of compounds with broad biological properties and wide application in pharmaceutical as well as agrochemical arenas. These diazaheterocycles are present in a wide variety of bioactive natural products as well as synthetic molecules that are good drug candidates constituting key structural units responsible for their pronounced therapeutic activities. Their rapidly growing uses and applications in medicinal and agrochemical arenas prompt the researchers for further studies on this important group of compounds. In this review, we hope to provide a brief overview of the important general methodologies and recent developments towards their synthesis and open the door for further progress in this area.