Rapid Ti(Oi-Pr)4 facilitated synthesis of α,α,α-trisubstituted primary amines by the addition of Grignard reagents to nitriles under microwave heating conditions

A series of carbinamines (α,α,α-trisubstituted amines) have been prepared in a simple and efficient one-pot procedure by the addition of Grignard reagents to a series of aliphatic, aromatic and heteroaromatic nitriles. The resulting magnesium imines are subsequently converted to the desired amine after treatment with Ti(Oi-Pr)₄ and additional microwave heating. Key to this procedure is the use of microwave heating for both steps of the reaction protocol, which significantly improves both reaction yields and reduces reaction times. In general, the Grignard addition reaction is complete within 5-10 min at 100 °C followed by conversion with Ti(Oi-Pr)₄ and additional microwave heating to give the target amines in good yields.     

Free Radical Synthetic Protocol for Benzothiazoles via Ring Opening of Benzotriazole: A Two‐step Organic Chemistry Experiment for Undergraduate and Postgraduate Students

The utility and advantages of benzotriazole methodology have been described for the practical synthesis of benzothiazoles. The two‐step synthetic procedure includes nucleophilic acyl substitution followed by benzotriazole ring cleavage under the free radical condition and subsequent cyclization via elimination of molecular nitrogen (N₂). This protocol requires cheap and readily available reagents, and moreover easy to handle, thus can be used to teach undergraduate and postgraduate students about the importance of benzotriazole moiety in organic synthesis, ring cleavage chemistry, cyclization reactions, and use of industrial waste in free radical reactions. Students can also learn some important and common techniques useful in organic chemistry such as monitoring of organic reaction using thin‐layer chromatography and UV, microwave (MW) technique for the synthesis, and column chromatography for the product isolation and structure determination through NMR, MS, and IR spectral analysis of the pure compounds.     

Acetamide/SO2Cl2 as an efficient reagent for Friedel–Craft’s acylation of aromatic compounds under ultrasonic and microwave conditions

Acetamide/SO₂Cl₂ reagent has been developed for effective Friedel–Craft’s acylation of aromatic compounds. Acylation of aromatic compounds with acetamide/SO₂Cl₂ was much more effective and faster than analogous (acetamide/SOCl₂) and (acetamide/POCl₃) reagents even under conventional conditions. However, microwave and ultrasonic assisted reactions afforded high yields of products in very short reaction times (30–40 min under sonication and 3–4 min under microwave assisted conditions).     

Microwave assisted solid additive effects in simple dry chlorination reactions with n-chlorosuccinimide

Solid additives participate in the dry microwave assisted chlorination reaction of N-chlorosuccinimide with the xylenes affecting both yields and chemoselectivities. Total yields can be increased up to nine times for simple alkylaromatics and chemoselectivities can be altered according to the desired ring or α-side chlorination product by choosing the appropriate additive. We believe that in these reactions the solid additives play a very important role by increasing yields and affecting chemoselectivities, as well as behaving as microwave energy absorbers that consequently aid the transfer of heat to the active reagents.     

Iron-Catalyzed Cross-Coupling Reactions of Alkyl Grignards with Aryl Chlorobenzenesulfonates

Aryl sulfonate esters are versatile synthetic intermediates in organic chemistry as well as attractive architectures due to their bioactive properties. Herein, we report the synthesis of alkyl-substituted benzenesulfonate esters by iron-catalyzed C(sp²)–C(sp³) cross-coupling of Grignard reagents with aryl chlorides. The method operates using an environmentally benign and sustainable iron catalytic system, employing benign urea ligands. A broad range of chlorobenzenesulfonates as well as challenging alkyl organometallics containing β-hydrogens are compatible with these conditions, affording alkylated products in high to excellent yields. The study reveals that aryl sulfonate esters are the most reactive activating groups for iron-catalyzed alkylative C(sp²)–C(sp³) cross-coupling of aryl chlorides with Grignard reagents.     

新型有机镁试剂的研究进展

介绍了双格氏试剂、镁杂碳环化合物和含有多官能团的格氏试剂的制备、反应化学及在有机合成中的应用等。     

Nano-Co3O4-catalyzed microwave-assisted one-pot synthesis of some seleno [2 , 3-b ] pyridine/quinoline derivatives

For the efficient synthesis of transition-metal cobalt oxide nanoparticles (Co₃O₄ NPs) without using any costly and toxic solvent or complicated equipment, the co-precipitation method was used in this work. Using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), UV–Vis spectrophotometry, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), the prepared Co₃O₄ NPs were characterized and identified. The influence of prepared Co₃O₄ NPs on the developmental synthesis of some selenopyridine/quinoline derivatives under different microwave irradiation powers and irradiation times was investigated via click (reaction) chemistry. The reusable Co₃O₄ nanoparticles have high catalytic activity under microwave irradiation for the synthesis of organoselenium compounds with higher yields (>?90%), milder reaction conditions and shorter time without significantly decreasing the reaction rates and yields.

     

Catalytic Asymmetric Syntheses of Alkylidenecyclopropanes from Allenoates with Donor-Acceptor and Diacceptor Diazo Reagents

The first diastereo- and enantioselective cyclopropanation reactions of electron-deficient allenes with donor-acceptor and diacceptor diazo reagents are described. The desired enantioenriched alkylidenecyclopropanes (ACPs) were obtained in high yields with high diastereo- and enantioselectivities in the presence of Rh₂((S)-TCPTAD)₄ or Rh₂((R)-BTPCP)₄ catalysts (up to 95 % yield, >95 : 5 d.r. and 99 : 1 e.r.). This methodology gave a direct access to ACPs bearing multiple electron-deficient substituents and allows to further expand the availability of ACPs chemistry. Interestingly, during the examination of the scope of this reaction, the asymmetric intramolecular C−H insertion reaction into tert-butyl group was observed as a side reaction with up to 94 : 6 e.r.     

Reaction of bromine with 4,5-dimethyl-1,4-cyclohexadiene-1,2-dicarboxylic acid: a green chemistry puzzle for organic chemistry students

Abstract

Bromination of an alkene is a typical addition reaction covered in an introductory organic chemistry course and laboratory. In this undergraduate organic chemistry laboratory exercise, students studied the bromination of a 4,5-dimethyl-1,4-cyclohexadiene-1,2-dicarboxylic acid. The reaction has an unexpected outcome as bromination yields the aromatic product, 4,5-dimethylphthalic acid. Green chemistry modification involves application of a “bromide/peroxide reaction” with NaBr/H₂O₂ in an acidic medium as an in situ source of bromine. The experiment was carried out as a two-day exercise and the students integrated molecular modeling, interpretation of mass spectra, knowledge of stability of organic compounds, and knowledge of the reaction mechanisms of addition and elimination to explain the experimental outcome.     

Convenient Preparation of Pyrano Benzopyranes in Aqueous Media

The three‐component reaction of aldehyde, malononitrile, and 4‐hydroxy coumarin has been efficiently performed in aqueous K₂CO₃ using a simple, clean, environmentally benign, novel procedure employing microwave irradiation. The observed yields and enhancement in reaction rates can be attributed to the uniform heating effect of microwave. The microwave‐accelerated reaction technique not only eliminates the use of external base and organic solvents but also requires only water in both the reaction step and workup, thus rendering the whole procedure into a truly ecofriendly protocol.     

Di- and triazidation of 3-chlorotetrafluoropyridine

3-Chlorotetrafluoropyridine and pentafluoropyridine readily react with an excess of sodium azide in dimethylsulfoxide at room temperature to give corresponding 2,4,6-triazido-3-chloro-5-fluoropyridine and 2,4,6-triazido-3,5-difluoropyridine in high yields. The reaction of asymmetric 3-chlorotetrafluoropyridine with two equimolar amounts of sodium azide under similar reaction conditions occurs regioselectively to give 2,4-diazido-5-chloro-3,6-difluoropyridine as a sole product. ¹⁹F, ¹³C and ¹⁵N NMR spectral characteristics of the triazides suggest that these compounds can be of interest as cross-linking reagents for polymer chemistry and as starting materials for organic synthesis.     

Recent advancements in palladium-catalyzed reactions involving molecular oxygen

Oxidation reactions have significant value in organic chemistry, having been in focus continuously due to the high efficiency in building up molecular complexity. In the past few decades, transition metal-catalyzed oxidation reactions have been significantly explored and have played important roles in organic synthesis. Compared to the widely-used oxidants, such as inorganic salts, peroxides, hypervalent iodine reagents and quinones, molecular oxygen (O₂), which is natural, inexpensive, and environmentally friendly, is a highly appealing oxidant in academic and industry area for green and sustainable chemistry. Recently, significant advances have been made in palladium-catalyzed reactions using O₂ as the oxidant. This critical review highlights some of the recent developments in molecular oxygen-involved Pd-catalyzed oxidation reactions with a focus on mechanistic strategies and new reaction developments.     

A Green Chemical Approach for Iodination of Pyrimidine Derivatives by Mechanical Grinding under Solvent-Free Conditions

The iodination of pyrimidines is usually carried out by using toxic reagents under acidic conditions, such as with sulfuric acid and nitric acid. To avoid toxic reagents, we developed a simple and eco-friendly approach for the iodination of pyrimidine derivatives under solvent-free conditions using solid iodine and AgNO₃ as an electrophilic iodinating reagent. The advantages of this method are the relatively short reaction time (20–30 min), simple set-up procedure, high yields (70–98%), and environmentally friendly reaction conditions. Our novel approach for the iodination of pyrimidines, as well as a variety of their derivatives, will contribute to the development of nucleobase-related drug candidates.     

Evolution of microwave irradiation and its application in green chemistry and biosciences

Microwave-assisted organic reactions have been applied as an effective technique in organic synthesis. Microwave irradiation often leads to shorter reaction times, increased yields, easier workup, matches with green chemistry protocols, and can enhance the region and stereo selectivity of reactions. In fact, the high usefulness of microwave-assisted synthesis encouraged us to increase the efficiency of several organic transformations and synthesis. High-speed microwave-assisted chemistry has attracted a considerable amount of attention in recent years and has been applied successfully in various fields of synthetic organic chemistry, proteins, peptides, drug discovery, and green chemistry. The various roles of microwave-assisted organic chemistry in green and sustainable chemistry are discussed, beginning with the strategies, technologies, and methods that were employed routinely at the time of the first reports of microwave applications. Microwave processing has several advantages over conventional sintering/heating, such as the reduction in cycle time, energy efficiency, eco-friendliness, and providing finer microstructures, leading to improved mechanical properties. Herein, we also describe the evolution of the microwave and some early applications of microwave assistance in the biomolecular sciences and treatment of solid malignant tumors.     

Microwave fluorination: a novel, rapid approach to fluorination with Selectfluor

Fluorination of electron rich aromatic systems with electrophilic fluorination reagents such as Selectfluor^® and Accufluor^® is a well-established process. Herein we report results from investigations into the use of such procedures to perform rapid, small-scale fluorinations under microwave irradiation. We have investigated the transformation with a range of different substrates and discuss the effects of two key factors, namely reaction time and choice of fluorination reagent. The use of Selectfluor^® in acetonitrile at 150 °C with microwave heating for 10 min affords products in comparable yields to those obtained by prolonged heating in acetonitrile at its reflux temperature.     

Cold microwave chemistry: synthesis using pre-cooled reagents

A novel experimental procedure for chemical reactions has been devised that involves mixing and then freezing the reagents (organic solvent-free) to a sub-zero temperature such as −30 °C. This frozen mixture is exposed to microwave irradiation for a brief period of time. The use of pre-cooled reagents may give a single product not obtained by traditional microwave irradiation at room temperature. Interestingly, such a product may provide information about mechanisms by identifying the first step of a multiple step reaction.     

Heck-type reaction of aryldiazonium silica sulfates

Abstract  

Aryldiazonium silica sulfates were employed as new and efficient reagents for Heck-type arylation reactions with styrene and methyl acrylate. The reactions were carried out in an organic solvent, in the presence of Pd(OAc)₂ as precatalyst without use of base and free ligand. The trans isomers of desired products, methyl cinnamates and stilbenes, were obtained with full conversion. Use of a catalytic amount of Pd(OAc)₂ produced the corresponding products in short reaction times and excellent yields.     

Microwave-assisted synthesis of bipyrazolyls and pyrazolyl-substituted pyrimidines

We describe the preparation of 1,4′-bipyrazolyls and 4-pyrazolylpyrimidines by the reaction of 2-pyrazolyl-3-dimethylamino acrylate and acrylonitrile with double nucleophilic reagents such as hydrazines, urea and guanidine. Reactions were performed under microwave irradiation in 5-60 min. This is a useful procedure for the preparation of valuable compounds with applications in medicinal and coordination chemistry.     

Functionalization of Metal–Organic Frameworks through the Postsynthetic Transformation of Olefin Side Groups

For the first time, the adaptability of the C?C double bond as a versatile precursor for the postsynthetic modification (PSM) of microporous materials was extensively investigated and evaluated. Therefore, an olefin‐tagged 4,4′‐bipyridine linker was synthesized and successfully introduced as pillar linker within a 9,10‐triptycenedicarboxylate (TDC) zinc paddle‐wheel metal–organic framework (MOF) through microwave‐assisted synthesis. Different reactions, predominately used in organic chemistry, were tested, leading to the development of new postsynthetic reactions for the functionalization of solid materials. The postsynthetic oxidation of the olefin side groups applying osmium tetroxide (OsO₄) as a catalyst led to the formation of a microporous material with free vicinal diol functionalities. The epoxidation with dimethyldioxirane (DMDO) enabled the synthesis of epoxy‐functionalized MOFs. In addition to that, reaction procedures for a postsynthetic hydroboration with borane dimethyl sulfide as well as a photoinduced thiol–ene click reaction with ethyl mercaptan were developed. For all of these PSMs, yields of more than 90 % were obtained, entirely maintaining the crystallinity of the MOFs. Since the direct introduction of the corresponding groups by means of pre‐synthetic approaches is hardly possible, these new PSMs are useful tools for the functionalization of porous solids towards applications such as selective adsorption, separation, and catalysis.     

Iodination of vanillin and subsequent Suzuki-Miyaura coupling: two-step synthetic sequence teaching green chemistry principles

ABSTRACT

A two-step synthetic sequence was developed for the undergraduate organic chemistry laboratory using vanillin as the starting material. The multi-step synthesis was designed to replace two traditional experiments teaching electrophilic aromatic substitution and carbon–carbon bond forming chemistries with greener transformations. Vanillin is iodinated using Oxone® and potassium iodide in refluxing water, and students are tasked with determining the position of aromatic substitution using ¹H NMR spectroscopy. The tan, shiny, pleasant-smelling iodovanillin is subsequently used in an aqueous Suzuki-Miyaura reaction with para-methylphenylboronic acid; strategically chosen to afford a second instructive ¹H NMR spectrum. Both conventional heating and microwave conditions can be employed for the palladium-catalyzed reaction. This synthetic sequence, successfully performed over multiple semesters by hundreds of students, models green chemistry principles through the use of a potentially renewable feedstock and safer reagents, the choice of water as a safer reaction solvent, and the employment of a catalytic reaction. Additionally, the sequence minimizes waste in teaching labs through use of an intermediate product.