Synthesis of N-alkyl-N′-aryl-piperazines via copper-catalyzed C–N bond formation

An efficient copper-catalyzed tandem synthesis of N-alkyl-N′-aryl-piperazines from 1,4-diaza-bicyclo[2.2.2]octane, alkyl halides, and aryl halides in the presence of copper(I) iodide and potassium tert-butoxide in DMSO is described.     

Polyethylene Glycols as Solvents for Anionic Activation: Synthesis of Thioacetates by Means of Potassium Thioacetate in Polyethylene Glycol 400

Recently, polyethylene glycols (PEGS) of various molecular weights have been proposed as solvent promoters for various reactions ^{1, 2}. We wish to report on the use of PEG 400 as solvent for the anionic activation of potassium thioacetate, which could be used for the preparation of alkyl and benzyl thioacetates from the corresponding halides or alcohol derivatives. The method can be synthetically significant, since from thioacetates the corresponding thiols can be easily prepared under a variety of mild conditions ³.     

Synthesis, characterization and thermal properties of small R2R2NX-type quaternary ammonium halides

Twenty-one R₂R^′₂N⁺X⁻ -type (R=methyl or ethyl, R^′=alkyl, X=Br or I) quaternary ammonium (QA) halides have been prepared by using a novel one-pot synthetic route in which a formamide (dimethyl-, diethylformamide, etc.) is treated with alkyl halide in the presence of sodium or potassium carbonate. The formation of QA halides was verified with ¹H-NMR, ¹³C-NMR, MS and elemental analysis. The crystal structures of four QA halides (two bromide and two iodide) were determined using X-ray single crystal diffraction, and the powder diffraction method was used to study the structural similarities between the single crystal and microcrystalline bulk material. The thermal properties of all compounds were studied using TG/DTA and DSC methods. The smallest compounds decomposed during or before melting. The decreasing trend of melting points was observed when the alkyl chain length was increased. The liquid ranges of 120-180 °C were observed for compounds with 5-6 carbon atoms in the alkyl chain. The low melting points and wide liquid ranges suggest potential applicability of these compounds for example as ionic liquids precursors.     

Alkali Metal and Trimethylsilyl Carbamoselenothioates – Synthesis,Structure, and some Reactions

This paper describes the synthesis and some reactions of potassium, rubidium, cesium and trimethylsilyl carbamoselenothioates. The potassium salts were synthesized in 70–80 % yields by reacting the corresponding thiocarbamoyl chlorides with potassium selenide in acetonitrile. Furthermore, the rubidium and cesium salts were obtained in good yields by treating the trimethylsilyl esters with the corresponding metal fluorides. The crystal structure of acetonitrile‐solvated potassium N,N‐dimethylcarbamoselenothioate consisted of dimeric units, featuring μ‐carbamoselenothioate anions associated with potassium cations that are located on the upper and lower sides of a plane involving two opposing carbamoselenothioate groups. These heavier alkali metal salts readily reacted with alkyl halides to give both S‐ and Se‐alkyl esters. The reaction of the potassium salts with trimethylsilyl chlorides forms S‐ and Se‐trimethylsilyl carbamoselenothioates which are in equilibrium. The reaction of the salts and silyl esters with organo Group‐14 and ‐15 elements halides gave exclusively the corresponding Se‐substituted products in good yields.     

Cocatalysis in phase-transfer catalyzed fluorination of alkyl halides and sulfonates

Phase-transfer catalyzed (PTC) fluorination of alkyl halides and sulfonates with solid KF proceeds efficiently when cocatalyst triphenyltin fluoride is used. The cocatalytic action of the tin compound consists in continuous formation of difluorotriphenylstannate anion that as the tetraalkyloammonium salt enter the solution where it reacts with alkyl halides to produce alkyl fluorides. The cocatalytic system was used to synthesis of 1,1-difluoroalkanes in two steps from aldehydes. A new kind of PTC was elaborated in which Ph₃SnF acts as phase transfer catalyst via continuous formation of potassium salts of diflurotriphenylstannate anions soluble in dipolar aprotic solvents. A new, simple and general method of synthesis of tetraalkylammonium and potassium salts of difluorotriorgano-tin, silicon and germanium anions is reported.     

SN2 reactions in the gas phase. Structure of the transition state

The alkylhalide-halide association ions, [RX₂]^? that are observed in the negative chemical ionization mass spectra of alkyl halides appear to be directly related to the corresponding S_N2 transition states in solution. ‘Frontside’ association of halide ions with bridgehead alkyl halides does not occur in our system. The Change in heats and entropies of association for the chloromethane series is consistent with delocalization in the [RX]₂^? ions.     

Potential N‐Heterocyclic Carbene Precursors in the Palladium‐Catalyzed Heck Reaction

A novel 1‐(cyclobutylmethyl)‐substi‐tuted imidazolidinium/benzimidazolium salts as N‐heterocyclic carbene (NHC) precursors were successfully synthesized and characterized by ¹H NMR, ¹³C NMR, IR, and elemental analysis techniques. These compounds were easily prepared from the reaction of N‐alkyl imidazoline/N‐alkyl benzimidazole with bromomethylcyclobutane in high yields. The in situ formed catalytic system derived from the NHC precursor and Pd(OAc)₂ was used in the Heck reaction between aryl halides and styrene with potassium hydroxide in water. The corresponding Heck products were obtained in good yields. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 24:77–83, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21065     

Rapid Synthesis of Alkyloxy Porphyrins Under Microwave Irradiation

Alkyloxy porphyrins have been prepared by direct coupling of 5-para-hydroxyphenyl-10,15,20-triphenylporphyrin and alkyl halides under microwave irradiation within several minutes. The length of the alkyl halides has no obvious effect on the yields and reaction time; however, the steric structure of the alkyl halides has a great impact on the reaction time. All the products were confirmed by ¹H NMR.     

Electrochemical NiH-Catalyzed C(sp3)−C(sp3) Coupling of Alkyl Halides and Alkyl Alkenes

Herein, an electrochemically driven NiH-catalyzed reductive coupling of alkyl halides and alkyl alkenes for the construction of Csp³−Csp³ bonds is firstly reported. Notably, alkyl halides serve dual function as coupling substrates and as hydrogen sources to generate NiH species under electrochemical conditions. The tunable nature of this reaction is realized by introducing an intramolecular coordinating group to the substrate, where the product can be easily adjusted to give the desired branched products. The method proceeds under mild conditions, exhibits a broad substrate scope, and affords moderate to excellent yields with over 70 examples, including late-stage modification of natural products and drug derivatives. Mechanistic insights offer evidence for an electrochemically driven coupling process. The sp³-carbon-halogen bonds can be activated through single electron transfer (SET) by the nickel catalyst in its low valence state, generated by cathodic reduction, and the generation of NiH species from alkyl halides is pivotal to this transformation.     

Theoretical Study on the Mechanism of Ni‐Catalyzed Alkyl–Alkyl Suzuki Cross‐Coupling

Ni‐catalyzed cross‐coupling of unactivated secondary alkyl halides with alkylboranes provides an efficient way to construct alkyl–alkyl bonds. The mechanism of this reaction with the Ni/ L1 ( L1 =trans‐N,N′‐dimethyl‐1,2‐cyclohexanediamine) system was examined for the first time by using theoretical calculations. The feasible mechanism was found to involve a Ni^I–Ni^III catalytic cycle with three main steps: transmetalation of [Ni^I( L1 )X] (X=Cl, Br) with 9‐borabicyclo[3.3.1]nonane (9‐BBN)R₁ to produce [Ni^I( L1 )(R₁)], oxidative addition of R₂X with [Ni^I( L1 )(R₁)] to produce [Ni^III( L1 )(R₁)(R₂)X] through a radical pathway, and C? C reductive elimination to generate the product and [Ni^I( L1 )X]. The transmetalation step is rate‐determining for both primary and secondary alkyl bromides. KOiBu decreases the activation barrier of the transmetalation step by forming a potassium alkyl boronate salt with alkyl borane. Tertiary alkyl halides are not reactive because the activation barrier of reductive elimination is too high (+34.7 kcal mol^?1). On the other hand, the cross‐coupling of alkyl chlorides can be catalyzed by Ni/ L2 ( L2 =trans‐N,N′‐dimethyl‐1,2‐diphenylethane‐1,2‐diamine) because the activation barrier of transmetalation with L2 is lower than that with L1 . Importantly, the Ni⁰–Ni^II catalytic cycle is not favored in the present systems because reductive elimination from both singlet and triplet [Ni^II( L1 )(R₁)(R₂)] is very difficult.     

Benzyl p-Toluenesulphonate as an 0-Benzylating Agent for the Protection of Phenols

Benzylation is a popular method of protecting phenolic groups during synthetic procedures. Benzyl ethers are stable to basic and mildly acidic conditions, but are cleaved readily by stronger acid, reduction, or most commonly by hydrogenolysis¹. Current methods of converting phenols into O-benzyl derivatives rely principally on the use of commercially available benzyl chloride or benzyl bromide and usually involve heating a mixture of the phenol and the halide with anhydrous potassium carbonate in dry acetone or DMF¹. To increase reactivity of the halide, potassium iodide may be added to the reaction mixture to generate benzyl iodide ‘in situ’. A major disadvantage of using alkyl halides in the preparation of phenolic ethers is the amount of simultaneous C-alkylation which can occur. Whilst C-alkylation is reduced by using polar aprotic solvents¹, it may still become an important side reaction during the alkylation of phenols containing phloroglucinol substitution patterns, yields of 0-alkyl derivatives decreasing markedly, and a complicated mixture of products generally ensues. In the cases of 0-methylation or -ethylation, such unwanted side-reactions can be minimised by employing dimethyl sulphate as the alkylating agents instead of the halides. No similar agents have been available for 0-benzylation reactions.     

A Convenient Synthesis of Thioacetates and Thiobenzoates Using Silica-Gel Supported Potassium Thioacetate

Abstract

A simple and efficient procedure has been developed for the synthesis of thioesters by a reaction of alkyl halides with silica-gel supported potassium thioacetate or thiobenzoate under mild conditions.     

Alkylation of Potassium 1-(N-Benzyloxycarbonylamino)alkylphosphonates and Phosphinates in the Presence of 18-Crown-6

During past several years we have been engaged in the synthesis of phosphono peptides, peptide analogues with phosphonic acid replacing C-terminal or N-terminal carboxylate moiety. These compounds are of interest not only because of their promise of direct practical applications^1,2 but also as a source of information about mechanisms of enzymatic reactions. ^1,3–5 Esters of N-blocked 1 -aminoalkylphosphonic and phosphinic acids are popularly used as starting substrates in multistep syntheses of phosphono peptides.^6–9 Although several methods for their preparation have been described ^6,10–13 the search for the new and useful methods of their synthesis is still in progress. In this paper we report that the use of complexes of potassium 1-(N- benzyloxycarbonylamiuo)alkylphosphonates and phosphates with 18-crown-6 as nucleophiles in the reaction with alkyl halides afforded the desired esters in good yields.     

Silafunctional Compounds in Organic Synthesis. XXXVII. Metalated (Allyl) Aminosilanes: Regioselective Coupling with Alkyl Halides to (E)-1-Alkenylsilanes with a Functional Group on Silicon

(E)-1-Alkenylsilanes with an amino or an alkoxy group on silicon can be conveniently synthesized by regioselective coupling of a potassium reagent derived from an allyl(amino)silane with alkyl halides.     

Photocatalyzed Aminomethylation of Alkyl Halides Enabled by Sterically Hindered N-Substituents

The catalytic C(sp³)−C(sp³) coupling of alkyl halides and tertiary amines offers a promising tool for the rapid decoration of amine skeletons. However, this approach has not been well established, partially due to the challenges in precisely distinguishing and controlling the reactivity of amine-coupling partners and their product homologues. Herein, we developed a metal-free photocatalytic system for the aminomethylation of alkyl halides through radical-involved C(sp³)−C(sp³) bond formation, allowing for the synthesis of sterically congested tertiary amines that are of interest in organic synthesis but not easily prepared by other methods. Mechanistic studies disclosed that sterically hindered N-substituents are key to activate the amine coupling partners by tuning their redox potentials to drive the reaction forward.     

Darstellung,Struktur und Reaktionsfähigkeit von Metallderivaten des 1-Propinphosphonsäure-diethylesters

Metallation of diethyl ester of 1-propynephosphonic acid (1-DEPP) is achieved by treatment with alkaline amides, calcium amid and calcium in liquid ammonia, with isopropylmagnesium chloride in ether or via metal exchange from the potassium derivative of 1-DEPP with copper(II) and cobalt(II) chloride resp.On the basis of IR-and¹H-NMR-spectra the calcium derivative appears as a mixture of an allene and its isomeric acetylene. The IR-spectrum of the lithium derivative is consistent with an analogous phenomenon while an acetylene structure is attributed only to the cobalt and copper derivatives. The alkylation of the potassium derivative with alkyl halides and the hydroxy-alkylation with benzaldehyde occur with low yield at the -position of the parent compound.

     

Practical synthesis of S-alkyl thiocarbamate herbicides by carbonylation of amines with carbon monoxide and sulfur

An industrial and economic carbonylation of amines with carbon monoxide and sulfur has been developed for the synthesis of S-alkyl thiocarbamate herbicides. In the presence of potassium carbonate and solvent DMSO, S-alkyl thiocarbamates, such as thiobencarb and orbencarb (herbicides) are synthesized in excellent yields from amines, carbon monoxide, sulfur, and alkyl halides under mild conditions (1 atm, 20 °C).     

A new type of phase-transfer catalysis via continuous transfer of fluoride anions to the organic phase in the form of potassium difluorotriphenylstannate

Fluorination of alkyl halides and sulfonates is efficiently executed in a liquid-solid phase-transfer catalysis system with Ph₃SnF as phase-transfer catalyst acting via continuous formation of lipophilic Ph₃SnF₂ anions entering the organic phase in the form of the potassium salt.     

Synthesis of S-Alkylisothiuronium Halides by Reaction of Thiourea with ω-(4-Hydroxyaryl)alkyl Halides

A number of new S-alkylisothiuronium salts were synthesized by reaction of -[4-hydroxy(methoxy)aryl]alkyl halides with thiourea. The resulting isothiuronium salts in aqueous solution react with sodium (potassium) halides to form halogen exchange products.     

Cyanogen Bromide Promoted Thiol Dimerization

The synthesis of alkyl thiocyanates by the reaction of thiols with cyanogen chloride has been known,¹ although it is generally supersede by the more convenient displacement of alkyl halides with alkali thio-cyanates.² We wish to describe the behavior of sodium thiolates toward cyanogen bromide.