Alkyl Aryl Research Articles

Design, Synthesis and Application of a Robust d3‐Methylthiolating Reagent†

Comprehensive SummaryA deuterated methylthiolating reagent with a broad spectrum, designated as DMTP, has been ingeniously formulated. This new reagent can be produced with high efficiency through the simple combination of commercially available methyl 3‐thiopropanoate and CD3I. This novel SCD3 reagent exhibits excellent reactivity with electrophiles such as alkyl iodides, benzyl chlorides, aryl halides (I, Br) and aryl triflates, resulting in high levels of deuterium content (99% D). Representative deuterated methylthiolated biomolecules, such as Sulfoxaflor, have been synthesized for use in pharmaceutical discovery and development.

Reaction of 4-Bpin-o-Carborane with Ketones: Sequential Carbon Vertex Alkylation and B-B Bond Activation.

Diboron compounds are important reagents in a series of transition metal catalyzed or metal-free borylation reactions. We describe herein a unique reactivity of 4-Bpin-o-carborane with ketones under basic conditions, leading to sequential cage carbon alkylation, B-B bond activation and unexpected O-migration. The reaction was compatible with a good substrate scope including dialkyl or alkyl aryl ketones. The reaction mechanism is also proposed, involving cage CH deprotonation, nucleophilic attack of ketone, and O-migration along with B-B bond cleavage.

Organophosphate esters in rural wastewater along the Yangtze river Basin: Occurrence, removal efficiency and environmental implications

Organophosphate esters (OPEs) discharged from rural domestic wastewater were one of the important sources of OPEs in receiving water bodies, which has posed a potential threat to the ecological environment. However, very little information on the characteristics of OPEs in the rural domestic wastewater is available. Herein, the occurrence, removal efficiency and environmental implication of OPEs in rural domestic wastewater treatment facilities (RD-WWTFs) along the Yangtze River Basin were investigated. Results indicated that the median concentrations of ΣAlkyl-OPEs, ΣHalogenated-OPEs, ΣAryl-OPEs and the total OPE (ΣOPEs) in influents were 28.28, 99.25, 10.22 and 136.84 ng/L, while the median concentrations of them in effluents were 25.80, 141.86, 7.98 and 173.31 ng/L, respectively. Undoubtedly, halogenated OPEs were the most abundant in both influent and effluent, followed by alkyl and aryl OPEs, and they accounted for average proportions of 69.50%, 19.96%and 10.54% for influents, and 78.16%, 16.14%and 5.71% for effluents, respectively. Specifically, tris(2-chloroisopropyl) phosphate (TCPP, median: 55.17 ng/L in influents and 85.75 ng/L in effluents) was the dominant contributor to the ΣOPEs concentrations with average proportions of 37.75% and 47.33% for influents and effluents, respectively. Moreover, the concentration ranks for most OPEs except for aryl OPEs from high to low were upper reaches > lower reaches > middle reaches. However, negative values of tris(2-chloroethyl)phosphate (TCEP, −32.4%), TCPP (−55.4%) and tris(1,3-dichloroisopropyl) phosphate (TDCPP, −26.3%) were observed. The removal rates of alkyl OPEs (10–20%) and aryl OPEs (20–30%) were also not sufficient. Ecological risk values of ΣOPEs showed that there were 2.44% of high risk, 31.7% of moderate risk and 41.5% of low risk for effluents; while 0.00%, 48.8% and 46.3% were exhibited in high, moderate and low risk for influents, indicating that very slight reduction in risk was achieved by the RD-WWTFs.

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.

Electroreductive Desulfurative Transformations with Thioethers as Alkyl Radical Precursors.

Thioethers are highly prevalent functional groups in organic compounds of natural and synthetic origin but remain remarkably underexplored as starting materials in desulfurative transformations. As such, new synthetic methods are highly desirable to unlock the potential of the compound class. In this vein, electrochemistry is an ideal tool to enable new reactivity and selectivity under mild conditions. Herein, we demonstrate the efficient use of aryl alkyl thioethers as alkyl radical precursors in electroreductive transformations, along with mechanistic details. The transformations proceed with complete selectivity for C(sp3 )-S bond cleavage, orthogonal to that of established transition metal-catalyzed two-electron routes. We showcase a hydrodesulfurization protocol with broad functional group tolerance, the first example of desulfurative C(sp3 )-C(sp3 ) bond formation in Giese-type cross-coupling and the first protocol for electrocarboxylation of synthetic relevance with thioethers as starting materials. Finally, the compound class is shown to outcompete their well-established sulfone analogues as alkyl radical precursors, demonstrating their synthetic potential for future desulfurative transformations in a one-electron manifold.

Electroreductive Desulfurative Transformations with Thioethers as Alkyl Radical Precursors**

AbstractThioethers are highly prevalent functional groups in organic compounds of natural and synthetic origin but remain remarkably underexplored as starting materials in desulfurative transformations. As such, new synthetic methods are highly desirable to unlock the potential of the compound class. In this vein, electrochemistry is an ideal tool to enable new reactivity and selectivity under mild conditions. Herein, we demonstrate the efficient use of aryl alkyl thioethers as alkyl radical precursors in electroreductive transformations, along with mechanistic details. The transformations proceed with complete selectivity for C(sp3)−S bond cleavage, orthogonal to that of established transition metal‐catalyzed two‐electron routes. We showcase a hydrodesulfurization protocol with broad functional group tolerance, the first example of desulfurative C(sp3)−C(sp3) bond formation in Giese‐type cross‐coupling and the first protocol for electrocarboxylation of synthetic relevance with thioethers as starting materials. Finally, the compound class is shown to outcompete their well‐established sulfone analogues as alkyl radical precursors, demonstrating their synthetic potential for future desulfurative transformations in a one‐electron manifold.

A Thiol-Free Route to Alkyl Aryl Thioethers.

Most existing methods for the synthesis of alkyl aryl thioethers require the use of mercaptans as the starting materials, which comes with practical limitations. Reactions of diaryliodonium salts with xanthate salts, easily prepared from the corresponding alcohols and CS2, under the developed conditions represent an operationally simple, thiol-free method for the synthesis of these valuable compounds. The protocol features high functional group tolerance and can be applied to the late-stage C-H functionalization and for the introduction of a CD3S group.

Tandem Cycloaddition of Azides to 3,3-Diaminoacrylonitriles (2-Cyanoacetamidines) and Cornforth-Type Rearrangement as an Approach to 5-Amino-1,2,3-triazole-4-N-substituted Imidamides.

An efficient base-catalyzed, metal-free method for the synthesis of 5-amino-1,2,3-triazole-4-N-sulfonyl- and arylimidamides, directed by the structure of the amidine group, has been developed. It is based on a previously unknown tandem process involving cycloaddition reaction to 3,3-diaminoacrylonitriles (2-cyanoacetamidines) with aryl(alkyl)sulfonyl or aryl azides and Cornforth-type rearrangement. During the reaction optimization, different factors were found to facilitate the title reaction, which include the use of a strong base and N-mono- or N,N'-disubstituted 3,3-diaminoacrylonitriles. The reaction is tolerant to variously N-monosubstituted and N,N'-disubstituted 3,3-diaminoacrylonitriles and to various aryl- and aryl/alkyl sulfonyl azides. The developed method has a broad scope and can be applied to obtain a variety of 5-amino-1,2,3-triazole-4-carbimidamides bearing at the N1 position alkyl, allyl, propargyl, benzyl, cycloalkyl, and heteroaryl substituents and sulfonyl and aryl substituents at the amidine group. Post-cyclization reactions of prepared 5-amino-1,2,3-triazoles with DMF-DMA DMA-DMF leads to 1,2,3-triazolo[4,5-d]pyrimidines, 8-aza purine analogues demonstrating the applicability of the prepared compounds in organic synthesis.

Phosphorus fluoride exchange: Multidimensional catalytic click chemistry from phosphorus connective hubs

Phosphorus Fluoride Exchange (PFEx) represents a cutting-edge advancement in catalytic click-reaction technology. Drawing inspiration from Nature's phosphate connectors, PFEx facilitates the reliable coupling of P(V)-F loaded hubs with aryl alcohols, alkyl alcohols, and amines to produce stable, multidimensional P(V)-O and P(V)-N linked products. The rate of P-F exchange is significantly enhanced by Lewis amine base catalysis, such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). PFEx substrates containing multiple P-F bonds are capable of selective, serial exchange reactions via judicious catalyst selection. In fewer than four synthetic steps, controlled projections can be deliberately incorporated along three of the four tetrahedral axes departing from the P(V) central hub, thus taking full advantage of the potential for generating three-dimensional diversity. Furthermore, late-stage functionalization of drugs and drug fragments can be achieved with the polyvalent PFEx hub, hexafluorocyclotriphosphazene (HFP), as has been demonstrated in prior research.

Preparation of multi band photothermal responsive bio-based superhydrophobic self-healing poly(siloxane-urethane) coating

In order to improve the poor hydrophobicity and single repair conditions of traditional self-healing polyurethane coatings, prepolymers were synthesized with bio-based polyol castor oil (CO), self-made alkyl aryl modified silicone polyols (Si-OH) and isophorone diisocyanate (IPDI), and 4,4'-dithiodianiline (ODD) was used as chain extender containing dynamic disulfide bond, 4-methylumbelliferone (4-MU), as a bio-based end capping agent with reversible ring structure, was polymerized step by step to prepare a photothermal responsive bio-based superhydrophobic self-healing poly(siloxane-urethane) coating (PUSi). In this paper, the effect of the amount of alkyl aryl modified silicone polyol (Si-OH) on the properties of PUSi was studied. The results showed that PUSi with different alkyl aryl modified silicone polyol additions could achieve self-healing under heating, UV irradiation and infrared light irradiation, and the maximum repair efficiency could reach 91% through optical microscope (OM), 3D profilometer and universal testing machine; The contact angle meter proved that the introduction of alkyl aryl modified silicone polyol greatly improved the hydrophobicity of PUSi, and the maximum water contact angle was 162°. The coating has broad application prospects in the fields of self-cleaning fabrics, super hydrophobic surfaces, special protective clothing and so on.

Nickel-Catalyzed Highly Selective Reductive Carbonylation Using Oxalyl Chloride as the Carbonyl Source

Nickel-catalyzed carbonylative cross-electrophile coupling which emerges as a powerful, efficient, and low-cost method for constructing challenging carbonyl derivatives has attracted increasing attention of organic chemists. To avoid the generation of a poisonous, volatile, and inert nickel carbonyl complex, it is critical to develop an efficient, cheap, and easily available CO surrogate. Oxalyl chloride, a cheap commercially available chemical, is one of the most versatile organic reagents used in chemical reactions. In this work, high chemoselectivity can be achieved with a 1:1:1 ratio of Ar–I to alkyl-I to oxalyl chloride. A wide range of alkyl aryl ketones which present an important class of molecules in synthetic and medicinal chemistry are accessed from alkyl halides, aryl iodides, under mild conditions. Primary and secondary alkyl iodides were suitable substrates. Various functional groups were well tolerated, affording up to 90% yields. This protocol was also used in the derivatization of natural products and drug molecules. Mechanistic investigation indicates that the reaction of Zn and oxalyl chloride under mild reaction conditions could release CO slowly. This knowledge should be useful for the further development of multicomponent carbonylative cross-coupling reactions.

Preparation of Vinylic Lithium Reagents from Silyl Enolates of Alkyl Aryl Ketones Using Lithium Arenide

AbstractThe preparation of vinylic lithium reagents from vinylic halides is a common practice in organic synthesis. However, the preparation of vinylic halides is not always straightforward. In this study, we propose the use of silyl enolates of alkyl aryl ketones as a readily available and efficient alternative for generating vinylic lithium species. Treatment of triisopropylsilyl enolates of alkyl aryl ketones with lithium naphthalenide or lithium 4,4’‐di‐t‐butylbiphenylide affords the corresponding vinylic lithium species. This preparation represents a reductive transformation of electron‐rich silyl enolates, which had remained unexplored. This process provides an alternative to the Shapiro reaction and has great potential for various applications in organic synthesis.

Ring Opening of Aziridines by Pendant Silanols Allows for Stereospecific Preparations of 1'-Amino-tetrahydrofurans.

We have developed a highly stereospecific cyclization of aziridine silanols into 1'-amino-tetrahydrofurans. Our protocol of stirring a substrate with 10 mol % Sc (OTf)3 and 1 equivalent of NaHCO3 in CH2Cl2 is mild and compatible with a range of activating aziridine N-substituents (including tosylates, mesylates, and carbamates) and functional groups on the alkyl chains (including substituted aryl rings, alkyl bromides, and alkyl ethers). In all cases examined, trans di-substituted aziridine silanols give products with an erythro configuration; conversely, cis di-substituted aziridine silanols give products with a threo configuration. While literature syntheses of 1'-amino-tetrahydrofurans exist, only one example, contemporaneous with our work, uses a similar cyclization for their construction. Control experiments demonstrate that, for this transformation, the silanol is not particularly privileged, and a variety of protecting groups on the alcohol (including other silicon protecting groups, benzyl ethers, and MOM ethers) are compatible with product formation.

Assessment of functional group in herbal formulation sathakuppai chooranam through fourier transform infrared spectroscopy

Background: The Sathakuppai chooranam is a single herbal medicine used in the treatment of Kumbavatham (Periarthritis). Objective: This study is aimed to evaluating the morphology and elemental charecterization of the Sathakuppai chooranam. Materials and methods: The ingredients were collected and purified and the drug was prepared as per Siddha literature Siddha Vaithiya Pathartha Guna vilakkam. It is subjected into characterisation through FT-IR analysis. Results: The FT-IR characterization showed the presence of functional groups like O-H stretching (carboxylic acid, alcohol molecule), N-H stretching (amine salt),C-H stretching (alkene), N-H stretching (amine salt), C-H stretching (alkene),C=C stretching (conjugate alkene, cyclic alkene,alpha beta unsaturated ketone), N=H bending (amine),O-H bending (carboxylic acid, alcohol),C-O stretching (alkyl aryl ether, primary alcohol), C-N stretching (amine), S=O stretching (sulfoxide), C=C bending (alkene), C-Br stretching (halo compund)which ensures the therapeutic effect of drug. Conclusion: The instrumental analysis FT-IR study for Sathakuppai chooranam shows the presence of functional groups through the stretch and bends which is responsible for its functional activity. The functional groups present in Sathakuppai Chooranam have analgesic, anti-inflammatory activities. This will ensure the efficacy and therapeutic effect of Sathakuppai Chooranam. This study forms the base for the pharmaceutical analysis of the Sathakuppai Chooranam.

Investigating the Mechanism of Ni-Catalyzed Coupling of Photoredox-Generated Alkyl Radicals and Aryl Bromides: A Computational Study.

Photoredox catalysis has emerged as an alternative to classical cross-coupling reactions, promoting new reactivities. Recently, the use of widely abundant alcohols and aryl bromides as coupling reagents was demonstrated to promote efficient coupling through the Ir/Ni dual photoredox catalytic cycle. However, the mechanism underlying this transformation is still unexplored, and here we report a comprehensive computational study of the catalytic cycle. We have shown that nickel catalysts can promote this reactivity very efficiently through DFT calculations. Two different mechanistic scenarios were explored, suggesting that two catalytic cycles operate simultaneously depending on the concentration of the alkyl radical.

Nickel‐catalyzed umpolung C[sbnd]S radical reductive cross coupling of S‐(trifluoromethyl)arylsulfonothioates with alkyl halides

A new cooperative nickel reductive catalysis and N,N-dimethylformamide-mediated strategy for umpolung CS radical reductive cross coupling of S-(trifluoromethyl)arylsulfonothioates with alkyl halides to produce alkyl aryl thioethers is described. This reaction features excellent selectivity, wide functionality tolerance, broad substrate scope, and facile late-stage modification of biologically relevant molecules. Mechanistic studies recognize initial generation of an amidyl radical anion via thermoinduced reduction of DMF with Sn, followed by umpolung reduction and single electron transfer of the nucleophilic sulfonyl moiety to form a sulphydryl radical and engage the Ni0/NiI/NiIII/NiI catalytic cycle.

Formal Cross-Coupling of Amines and Carboxylic Acids to Form sp3-sp2 Carbon-Carbon Bonds.

Amines and carboxylic acids are abundant synthetic building blocks that are classically united to form an amide bond. To access new pockets of chemical space, we are interested in the development of amine-acid coupling reactions that complement the amide coupling. In particular, the formation of carbon-carbon bonds by formal deamination and decarboxylation would be an impactful addition to the synthesis toolbox. Here, we report a formal cross-coupling of alkyl amines and aryl carboxylic acids to form C(sp3)-C(sp2) bonds following preactivation of the amine-acid building blocks as a pyridinium salt and N-acyl-glutarimide, respectively. Under nickel-catalyzed reductive cross-coupling conditions, a diversity of simple and complex substrates are united in good to excellent yield, and numerous pharmaceuticals are successfully diversified. High-throughput experimentation was leveraged in the development of the reaction and the discovery of performance-enhancing additives such as phthalimide, RuCl3, and GaCl3. Mechanistic investigations suggest phthalimide may play a role in stabilizing productive Ni complexes rather than being involved in oxidative addition of the N-acyl-imide and that RuCl3 supports the decarbonylation event, thereby improving reaction selectivity.

Sulfenate Anion Catalyzed Diastereoselective Synthesis of Aziridines.

Aziridines are highly valued synthetic targets in organic and medicinal chemistry. The organocatalytic synthesis of such structures with broad substrate scope and good diastereoselectivity, however, is rare. Herein, we report a broadly applicable and diastereoselective synthetic method for the synthesis of trans-aziridines from imines and benzylic or alkyl halides utilizing sulfenate anions (PhSO- ) as the catalyst. Substrates bearing heterocyclic aromatic groups, alkyl, and electron-rich and electron-poor aryl groups were shown to be compatible with this method (33 examples), giving good yields and high diastereoselectivities (trans : cis >20 : 1). Further functionalization of aziridines containing cyclopropyl or cyclobutyl groups was achieved through ring-opening reactions, with a cyclobutyl-substituted norephedrine derivative obtained through a four-step synthesis. We offer a mechanistic proposal involving reversible addition of the deprotonated benzyl sulfoxide to the imine to explain the high trans-diastereoselectivity.

Conversion of Racemic Alkyl Aryl Sulfoxides into Pure Enantiomers Using a Recycle Photoreactor: Tandem Use of Chromatography on Chiral Support and Photoracemization on Solid Support

Chiral sulfoxides are valuable in the fields of medicinal chemistry and organic synthesis. A recycle photoreactor utilizing the concept of deracemization, where a racemate is converted into a pure enantiomer, is developed and successfully applied in the syntheses of chiral alkyl aryl sulfoxides. The recycling system consists of rapid photoracemization using an immobilized photosensitizer and separation of the enantiomers via chiral high-performance liquid chromatography, and the desired pure chiral sulfoxides are obtained after 4-6 cycles. The key to the success of the system is the photoreactor site, wherein the photosensitizer 2,4,6-triphenylpyrylium is immobilized on the resin and irradiated (405 nm) to enable the rapid photoracemizations of the sulfoxides. As the green recycle photoreactor requires no chiral components, it should be a useful alternative system for application in producing chiral compounds.

Thioethers as Dichotomous Electrophiles for Site-Selective Silylation via C-S Bond Cleavage.

The development of aryl alkyl sulfides as dichotomous electrophiles for site-selective silylation via C-S bond cleavage has been achieved. Iron-catalyzed selective cleavage of C(aryl)-S bonds can occur in the presence of β-diketimine ligands, and the cleavage of C(alkyl)-S bonds can be achieved by t-BuONa without the use of transition metals, resulting in the corresponding silylated products in moderate to excellent yields. Mechanistic studies suggest that Fe-Si species may undergo metathesis reactions during the cleavage of C(aryl)-S bonds, while silyl radicals are involved during the cleavage of C(alkyl)-S bonds.