Efficient Regioselective Synthesis Research Articles

Efficient Regioselective Synthesis of Novel Ensembles of Organylselanyl-Functionalized Divinyl Sulfides and 1,3-Thiaselenoles under Phase Transfer Catalysis Conditions

Efficient regioselective synthesis of novel ensembles of organylselanyl-functionalized 1,3-thiaselenoles and divinyl sulfides in high yields under phase transfer catalysis conditions was developed. The methodology is based on the generation of sodium [(Z)-2-(vinylsulfanyl)ethenyl]selenolate and 1,3-thiaselenol-2-ylmethylselenolate, which were involved in a nucleophilic addition reaction with activated alkenes such as acrylonitrile, acrylamide, methyl vinyl ketone, methyl, and ethyl acrylates. In the case of methyl vinyl ketone, the reaction was accompanied by the hydrogenation of the carbonyl group. Methylene chloride was involved in the nucleophilic substitution reaction with sodium [(Z)-2-(vinylsulfanyl)ethenyl]selenolate and 1,3-thiaselenol-2-ylmethylselenolate to afford new polyunsaturated compounds with several sulfur and selenium atoms.

Novel MCM-41 Supported Dicationic Imidazolium Ionic Liquids Catalyzed Greener and Efficient Regioselective Synthesis of 2-Oxazolidinones from Aziridines and Carbon Dioxide.

A type of MCM-41 supported dicationic imidazolium ionic liquid nanocatalyst has been synthesized and found to be competent for the synthesis of 2-oxazolidinones through the sustainable chemical conversion of CO2 with aziridines. It was shown that the highest efficiency was achieved in the cycloaddition of a series of aziridines and CO2 in the presence of a catalytic amount of the solid catalyst MCM-41@ILLaCl4 under mild conditions. Merits of this meticulously designed protocol are the use of a novel supported ionic liquid catalyst, the easy work-up process, good to excellent yields, a short reaction time, and purification without column chromatography. Overall, the present protocol of synthesizing 2-oxazolidinones under cocatalyst- and solvent-free conditions using MCM-41@ILLaCl4 is promising for industrial applications.

Visible Light Organo‐Photocatalytic Synthesis of 3‐Imidazolines

AbstractAn efficient regioselective synthesis of tetrasubstituted 3‐imidazolines under organo‐photocatalytic conditions has been developed through formal [3+2]‐cycloaddition between 2H‐azirines and N‐tosyl benzylidene imines. The products were isolated in high yields and as a separable mixture of diastereoisomers in most of the cases. The mild reaction conditions employing an organic dye as photocatalyst, excellent functional group tolerance, and high regioselectivity are notable features of the current protocol.

Ag2O-Induced Regioselective Huisgen Cycloaddition for the Synthesis of Fully Substituted Pyrazoles as Potential Anticancer Agents.

Efficient regioselective synthesis of novel fully substituted pyrazoles has been achieved through Huisgen cycloaddition reaction of δ-acetoxy allenoates with hydrazonoyl chlorides by the addition of Ag2O. The present approach offers the advantages of simpleness, high efficiency, mild conditions, wide substrate scope, and good-to-excellent regioselectivities. The strategy could be performed on a large-scale pattern to allow access to structurally versatile pyrazoles, of which a key intermediate of lonazolac (303), a nonsteroidal anti-inflammatory drug, could be synthesized efficiently. Moreover, several pyrazoles show obvious growth-inhibitory activity of Huh-7 cells, expected as potential anticancer agents.

Transition Metal‐ and Oxidant‐Free Regioselective Synthesis of 3,4,5‐Trisubstituted Pyrazoles by Means of [3+2] Cycloaddition Reactions

AbstractA highly efficient regioselective synthesis of 3,4,5‐trisubstituted pyrazoles via transition metal‐ and oxidant‐free, three component [3+2] cycloaddition with thiazolidinedione chalcones, benzaldehydes and N‐tosylhydrazine is described. The reaction proceeds through C−C and C−N bond formations under mild reaction conditions to produce structurally diverse polysubstituted pyrazoles in moderate to good yields.

Tetraarylphosphonium salt-catalyzed formal [3+2] cycloaddition between epoxides and trichloroacetonitrile for the synthesis of β-amino alcohol derivatives.

Efficient regioselective synthesis of β-amino alcohol derivatives, including enantioenriched ones, by a tetraarylphosphonium salt-catalyzed coupling reaction of epoxides with trichloroacetonitrile is described. Formal [3+2] cycloaddition, followed by hydrolysis, proceeded smoothly to afford N-protected β-amino alcohols in good yields.

Facile generation of bridged medium-sized polycyclic systems by rhodium-catalysed intramolecular (3+2) dipolar cycloadditions

Bridged medium-sized bicyclo[m.n.2] ring systems are common in natural products and potent pharmaceuticals, and pose a great synthetic challenge. Chemistry for making bicyclo[m.n.2] ring systems remains underdeveloped. Currently, there are no general reactions available for the single-step synthesis of various bridged bicyclo[m.n.2] ring systems from acyclic precursors. Here, we report an unusual type II intramolecular (3+2) dipolar cycloaddition strategy for the syntheses of various bridged bicyclo[m.n.2] ring systems. This rhodium-catalysed cascade reaction provides a relatively general strategy for the direct and efficient regioselective and diastereoselective synthesis of highly functionalized and synthetically challenging bridged medium-sized polycyclic systems. Asymmetric total synthesis of nakafuran-8 was accomplished using this method as a key step. Quantum mechanical calculations demonstrate the mechanism of this transformation and the origins of its multiple selectivities. This reaction will inspire the design of the strategies to make complex bioactive molecules with bridged medium-sized polycyclic systems.

Efficient Regioselective Synthesis of Novel Condensed Sulfur-Nitrogen Heterocyclic Compounds Based on Annulation Reactions of 2-Quinolinesulfenyl Halides with Alkenes and Cycloalkenes.

The preparation of novel reagents 2-quinolinesulfenyl chloride and bromide based on available 2-mercaptoquinoline has been described. This approach opens up opportunities for the introduction of 2-quinolinesulfenyl chloride and bromide into organic synthesis. Regioselective synthesis of novel 1,2-dihydro[1,3]thiazolo[3,2-a]quinolin-10-ium derivatives in high yields has been developed by annulation reactions of 2-quinolinesulfenyl chloride and bromide with alkenes. Condensed tetracyclic products have been obtained by the reactions of 2-quinolinesulfenyl chloride and bromide with cycloalkenes. The opposite regiochemistry in the reactions with styrene, isoeugenol and 1-alkenes was discussed.

Ionic Liquid Catalyzed Efficient Regioselective Synthesis of 1,4-Disubstituted 1,2,3-Triazoles Under Metal and Solvent Free Conditions

Background: Catalyzed organic reactions avoiding the use of metal salts, metal complexes and organometallic compounds have tremendous applications especially within sensitive biological systems. The current work is an effort towards metal and solvent-free organo-catalyzed reactions. Objective: Unprecedented, one-pot regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles through azide-aldehyde (3+2) organo-click cycloaddition under metal and solvent-free conditions is described. Methods: The method presents a convenient approach towards the synthesis of functionally versatile 1,4-disubstituted 1,2,3-triazoles from easily accessible substrates using recyclable 1,8-diazabicyclo[ 5.4.0]undec-7-ene (DBU)-based ionic liquids as catalysts. Results: 1,4-disubstituted 1,2,3-triazoles were obtained in moderate to excellent yield using azidealdehyde (3+2) organo-click cycloaddition under metal and solvent-free conditions. Conclusion: The procedure reported herein for the synthesis of 1,4-disubstituted 1,2,3-triazoles is straightforward, greener, devoid of tedious workups and chromatographic separation.

Fast and efficient regioselective synthesis of a novel eight membered ring system, 5H-benzo[f]pyrimido[4,5-b][1,5]oxazocine

An efficient two-steps strategy for the regioselective synthesis of the benzo[f]pyrimido[4,5-b][1,5]oxazocine as a novel tricyclic system has been developed via inter- and intramolecular heterocyclization of 2,4-dichloro-5-(chloromethyl)-6-methylpyrimidine and 2-aminobenzylalcohol in room temperature and short reaction times under mild conditions, followed amination with some secondary amines. 2D-NOESY and HMBC NMR spectroscopy was performed to gain the true regioisomer of the reaction, as well.

An Efficient Regioselective Synthesis of 8-Formylhomoisoflavonoids with Neuroprotective Activity by Enhancing Autophagy.

6-Formylisoophiopogonone B (7a) and 8-formylophiopogonone B (7b), two natural products isolated from Ophiopogon japonicus, represent a subgroup of rare 6/8-formyl/methyl-homoisoflavonoid skeletons. Herein we report an efficient method for the synthesis of these formyl/methyl-homoisoflavonoids. The synthesized compounds were evaluated for their neuroprotective effects on the MPP+-induced SH-SY5Y cell injury model and showed marked activity. Exploration of the neuroprotective mechanisms of compound 7b led to an increased expression of autophagy marker LC3-II and down-regulation of autophagy substrate p62/SQSTM1. Molecular docking studies showed that 7b may prevent the inhibition of the classic PI3K-AKT-mTOR signaling pathway by interfering with the human HSP90AA1.

Efficient Regioselective Synthesis of Novel Water-Soluble 2H,3H-[1,4]thiazino[2,3,4-ij]quinolin-4-ium Derivatives by Annulation Reactions of 8-quinolinesulfenyl Halides.

Regioselective synthesis of novel 2H,3H-[1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives has been developed by annulation reactions of 8-quinolinesulfenyl halides with vinyl chalcogenides (vinyl ethers, divinyl sulfide, divinyl selenide and phenyl vinyl sulfide) and tetravinyl silane. The novel reagent 8-quinolinesulfenyl bromide was used in the annulation reactions. The influence of the substrate structure and the nature of heteroatoms on the direction of the reactions and on product yields has been studied. The opposite regiochemistry was observed in the reactions with vinyl chalcogenides and tetravinyl silane. The obtained condensed heterocycles are novel water-soluble functionalized compounds with promising biological activity.

An efficient regioselective synthesis of N-alkylated purine-triazole analogues

Nitrogen rich purine adduct (2) was prepared by reaction of 2,6-dichloro purine (1) with hydrazine hydrate was converted to hybrid purine-triazole ring (4) by a simple cyclisation process (con. HCl & methanol) on reaction with 3-phenoxy benzaldehyde. The regioselectivity of synthesized adducts was carried out by simple spectroscopic techniques i.e. IR, 1 H NMR & 13 C NMR spectra. These studies gave an idea regarding replacement of chlorine out of C-2 or C-6 position. Novelty was introduced by alkyl substation at N -9 position of imidazole ring and at –NH of triazole ring and a series of 4-chloro-5a , 6-dihydro-1 , 6-dialkylated-8-(3-phenoxyphenyl)-1H-[1 , 2 , 4]triazolo[3 , 4-e]purine (5a-5g) hybrids were synthesized.

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction.

The reaction of 2-(bromomethyl)-1,3-thiaselenole with potassium selenocyanate proceeded via a rearrangement with ring expansion, leading to a six-membered 2,3-dihydro-1,4-thiaselenin-2-yl selenocyanate (kinetic product) which in turn underwent rearrangement with ring contraction to a 1,3-thiaselenol-2-ylmethyl selenocyanate (thermodynamic product). These rearrangements occurred by a nucleophilic attack of the selenocyanate anion at two different carbon atoms of the seleniranium intermediate. The efficient regioselective synthesis of alkyl, allyl, 2-propynyl, benzyl, 4-fluorobenzyl, and 2-pyridinylmethyl 1,3-thiaselenol-2-ylmethyl selenides was developed based on the generation of sodium 1,3-thiaselenol-2-ylmethylselenolate from 1,3-thiaselenol-2-ylmethyl selenocyanate or bis(1,3-thiaselenol-2-ylmethyl) diselenide followed by nucleophilic substitution reactions. Sodium 1,3-thiaselenol-2-ylmethylselenolate underwent nucleophilic addition to alkyl propiolates in a regio- and stereoselective manner affording 1,3-thiaselenol-2-ylmethyl vinyl selenides in high yields predominantly with Z-configuration. Not a single representative of the 1,3-thiaselenol-2-ylmethyl selenide scaffold has been previously described in the literature.

Halo-heterocyclization of butenyl(prenyl)thioethers of 4,5-diphenyl-1,2,4-triazol-3-thiole into triazolo[5,1-b] [1,3]thiazinium systems: experimental and theoretical evolution

A facile and highly efficient regioselective synthesis of partially saturated triazolo[5,1-b][1,3]thiazinium salts by the electrophilic heterocyclization of the butenyl thioethers of 4,5-diphenyl-1,2,4-triazol-3-thiol with halogens was developed. Under developed conditions, electrophilic cyclization reactions proceeded smoothly and cleanly and the corresponding fused products were obtained in high yields in all cases examined. Herein, we also report the studying of the regiochemistry of this process using computer simulation methods, XDR, and spectral investigations for explaining of electrophilic cyclization mechanism and solving of final products structure.

An efficient regioselective three-component synthesis of tetrazoloquinazolines using g-C3N4 covalently bonded sulfamic acid

A green and cost-effective protocol developed using covalently bonded sulfamic acid graphitic carbon nitride (g-C3N4/NHSO3H) for the synthesis of quinazoline derivatives using three-component condensation reaction of benzaldehyde, 2‐aminotetrazole and dimedone. The XRD, TEM, SEM, EDX and FT-IR techniques were used to identify the physical and chemical properties of g-C3N4/NHSO3H. The -NHSO3H solid catalyst, was reused eight times without significant decrease in activity. This catalyst acts as a benign acid catalyst, a green protocol of a one-pot due to having significant advantages such as active sites containing SO3H groups, reacting under mild conditions with high efficiency as well as the ability to recover and reuse without decreasing activity.

The use of enaminones and enamines as effective synthons for MSA-catalyzed regioselective synthesis of 1,3,4-tri- and 1,3,4,5-tetrasubstituted pyrazoles

In the present work, an efficient regioselective synthesis of 1,3,4-tri- and 1,3,4,5-tetrasubstituted pyrazoles via a methanesulfonic acid (MSA)-catalyzed reaction of hydrazones with enaminones or enamines is reported.

Synthesis of novel pyrazole incorporating a coumarin moiety (PC) for selective and sensitive Co2+detection

An efficient regioselective synthesis of a novel pyrazole derivative containing a coumarin moiety was achieved, which was electrodeposited as PC/Nafion/GCE sensor probe to detect the selective Co2+ions for the safety of environment and healthcare fields.

Reaction of CF3-ynones with methyl thioglycolate. Regioselective synthesis of 3-CF3-thiophene derivatives

Efficient regioselective synthesis of 3-CF3-substituted thiophene derivatives was elaborated using addition of methyl thioglycolate to CF3-ynones in the presence of sodium methoxide.

Benzo[b]carbazole and indole derivatives as emitters for non-doped deep-blue organic light emitting diodes

Derivatives of indole and benzo[b]carbazole were prepared by employing efficient regioselective acid-catalysed synthesis of 1H, 1-methyl and 1-naphthylindole with o-phthaldialdehyde. The synthesized compounds were characterized by NMR, IR and mass spectrometries. They form molecular glasses with glass transition temperatures ranging from 86 to 116 °C. Naphthyl-substituted derivatives showed high thermal stabilities with 5% weight loss temperatures of 409 and 413 °C, while their methyl-substituted counterparts exhibited by ca. 90 °C lower 5% weight loss temperatures. Their solutions exhibited blue emission with quantum yields of 67%. Ionization potentials of the compounds estimated by cyclic voltammetry are in the range of 5.49–5.65 eV, while the values obtained using photoelectron emission in air method are in the range of 5.16–5.28 eV. The layers of the compounds exhibited ambipolar charge transport with time-of-flight charge drift mobility values well exceeding 10−3 cm2/(Vs) at high electric fields. Non-doped naphthylindole and benzo[b]carbazole derivative based device emitted deep-blue light with the maximum intensity at 410 nm and CIE of (0.21, 0.16), and it exhibited a maximum external quantum efficiency of 3.4%.