A General Approach to Substituted Benzimidazoles and Benzoxazoles via Heterogeneous Palladium‐Catalyzed Hydrogen‐Transfer with Primary Amines

The synthesis of benzimidazoles starting from o‐phenylenediamines and amines in the presence of palladium on charcoal as catalyst is reported. Under microwave dielectric heating it is possible to use a tertiary, a secondary, and even a primary amine as the substrate for a palladium‐mediated process to get 2‐substituted or 1,2‐disubstituted benzimidazoles, depending on the nature of the o‐phenylenediamine employed. Primary amines are the most suitable reagents for the atom economy of the overall process that resulted to be general as several different substituted benzimidazoles were obtained in good yield. Benzoxazoles can be also prepared starting from primary amines and o‐aminophenol. The reaction is also highly selective as no (poly)‐alkylated phenylenediamines or cross‐contaminated benzimidazoles are obtained starting from N‐monoalkylphenylenediamines. This behavior was interpreted as a scarce aptitude to dehydrogenation of the methylene bonded to the aromatic NH of N‐alkylarylamines. The experiments carried out consent to draw an almost complete picture of the reaction pathways occurring during the process. The catalyst can be recycled several times and, although far from optimal performances, catalyst TON=90 is encouraging for further large‐scale optimization protocols. In addition, the palladium on charcoal‐catalyzed microwave‐assisted reaction of o‐phenylenediamine gives de‐alkylation of tertiary amines and transformation into the secondary ones.     

Kinetics of o‐Xylene Combustion over a Pt/Alumina Catalyst

o‐Xylene combustion in air over a Pt/γ‐Al₂O₃ catalyst was investigated in a laboratory reactor at low concentrations typical for depollution applications. The results evidenced a slightly negative influence of o‐xylene concentration on combustion rate. A kinetic model of the combustion process was developed by using the Langmuir‐Hinshelwood mechanism, assuming the surface reaction between adsorbed oxygen atoms and adsorbed o‐xylene molecules as controlling step. The rate expression includes the influences of o‐xylene and water adsorption on the active centers of the catalyst. The estimation of rate expression parameters is based on o‐xylene conversion measurements obtained under conditions free of influences of physical steps.     

Asymmetric,Regioselective Bromohydroxylation of 2‐Aryl‐2‐propen‐1‐ols Catalyzed by Quinine‐Derived Catalysts

The asymmetric bromohydroxylation of 2‐aryl‐2‐propen‐1‐ols catalyzed by quinine‐derived bifunctional catalyst has been developed. The regioselectivity was controlled by employing a boronate ester as tether which was formed in situ and enantioselectivity was introduced by taking advantage of a quinine‐derived bifunctional catalyst which activated the boronate ester and N‐bromosuccinimide (NBS) at the same time. Chiral bromohydrin, which is a useful feedstock in organic synthesis, was produced in moderate to excellent enantioselectivity in a two‐step reaction sequence.     

Cutting Long Syntheses Short: Access to Non‐Natural Tyrosine Derivatives Employing an Engineered Tyrosine Phenol Lyase

The chemical synthesis of 3‐substituted tyrosine derivatives requires a minimum of four steps to access optically enriched material starting from commercial precursors. Attempting to short‐cut the cumbersome chemical synthesis of 3‐substituted tyrosine derivatives, a single step biocatalytic approach was identified employing the tyrosine phenol lyase from Citrobacter freundii. The enzyme catalyses the hydrolysis of tyrosine to phenol, pyruvate and ammonium as well as the reverse reaction, thus the formation of tyrosine from phenol, pyruvate and ammonium. Since the wild‐type enzyme possessed a very narrow substrate spectrum, structure‐guided, site‐directed mutagenesis was required to change the substrate specificity of this C C bond forming enzyme. The best variant M379V transformed, for example, o‐cresol, o‐methoxyphenol and o‐chlorophenol efficiently to the corresponding tyrosine derivatives without any detectable side‐product. In contrast, all three phenol compounds were non‐substrates for the wild‐type enzyme. Employing the mutant, various L ‐tyrosine derivatives (3‐Me, 3‐OMe, 3‐F, 3‐Cl) were obtained with complete conversion and excellent enantiomeric excess (>97%) in just a single ‘green’ step starting from pyruvate and commercially available phenol derivatives.     

Synthesis of Benzimidazole‐Substituted Arylboronic Acids via Aerobic Oxidation of 1,2‐Arylenediamines and Formyl‐Substituted Aryl MIDA Boronates using Potassium Iodide as a Catalyst

A highly efficient protocol for the synthesis of benzimidazole‐substituted arylboronic acids was developed via aerobic oxidative cyclization of 1,2‐aryldiamines and formyl‐substituted aryl MIDA (N‐methyliminodiacetic acid) boronates using potassium iodide as a nucleophilic catalyst. Furthermore, a one‐pot protocol for the synthesis of benzimidazole‐substituted arylboronic acids from 1,2‐phenylenediamines and formyl‐substituted arylboronic acids was developed without the isolation of any intermediates. The resulting boronic acids were further subjected to Suzuki–Miyaura coupling reactions without isolation, leading to diaryl‐substituted benzimidazoles with only one separation step.

     

Fully Enzymatic Resolution of Chiral Amines: Acylation and Deacylation in the Presence of Candida antarctica Lipase B

A fully enzymatic methodology for the resolution of chiral amines has been demonstrated. Candida antarctica lipase B (CaLB)‐catalyzed acylation with N‐methyl‐ and N‐phenylglycine, as well as analogues having the general formula R¹ X CH₂CO₂R² (R¹=Me, Ph; X=O, S) afforded the corresponding enantioenriched amides, which were subsequently enzymatically hydrolyzed. Surprisingly, CaLB also proved to be the catalyst of choice for this latter step. The heteroatom in the acyl donor profoundly influences both the enzymatic acylation and deacylation; the O‐substituted reagents performed best with regard to enantioselectivity as well as reaction rate in synthesis and hydrolysis.     

An Efficient Method for the Selective Iridium‐Catalyzed Monoalkylation of (Hetero)aromatic Amines with Primary Alcohols

An efficient multi‐gram scale synthesis protocol of a variety of P,N ligands is described. The synthesis is achieved in a two‐step reaction. First, the amine is deprotonated and subsequently the chlorophosphine is added to yield the corresponding P,N ligand. Deprotonation of the amine is normally achieved with n‐BuLi at low temperature, but for the preparation of ligands with a 2,2′‐dipyridylamino backbone and phosphines with a high steric demand KH has to be employed in combination with reaction temperatures of 110 °C for the salt metathesis step. The reaction of two equivalents of a selected P,N ligand with one equivalent of the iridium complex [IrCl(cod)]₂ (cod=1,5‐cyclooctadiene) affords P,N ligand‐coordinated iridium complexes in quantitative yield. X‐Ray single crystal structure analysis of one of these complexes reveals a monomeric five‐coordinated structure in the solid state. The iridium complexes were used to form catalysts for the N‐alkylation of aromatic amines with alcohols. The catalyst system was optimized by studying 8 different P,N ligands, 9 different solvents and 14 different bases. Systematic variation of the substrate to base and the amine to alcohol ratios as well as the catalyst loading led to optimized catalytic reaction conditions. The substrate scope of the developed catalytic protocol was shown by synthesizing 20 different amines of which 12 could be obtained in isolated yields higher than 90%. A new efficient catalyst system for the selective monoalkylation of primary aromatic and heteroaromatic amines with primary aromatic, heteroaromatic as well as aliphatic alcohols has been established. The reaction proceeds with rather moderate catalyst loadings.     

Three‐Step One‐Pot Synthesis of Imidazo[2,1‐b]chalcogenazoles via Intramolecular Cyclization of N‐Alkynylimidazoles

Imidazo‐chalcogenazoles are easily accessible from the corresponding N‐alkynylimidazoles by a three‐step, one‐pot chalcogenation reaction. The generality of this reaction has been established with various substituted N‐alkynylimidazoles as well as elemental chalcogens. By accessing the key intermediate 2‐chalcogenolate‐N‐alkynylimidazole it was also possible to prepare dichalcogenide derivatives.     

Convenient synthesis of sulfonamides from amines and p‐toluene sulfonyl chloride mediated by crosslinked poly(4‐vinylpyridine)

A general, mild, and convenient method has been developed for the synthesis of various N‐substituted and N, N‐disubstituted sulfonamides, as a class of sulfa drugs, from the corresponding amines and p‐toluene sulfonyl chloride in the presence of readily available crosslinked poly(4‐vinylpyridine) as a catalyst, base or polymeric substrates. The use of polymeric catalyst simplifies routine sulfonylation of amines because it eliminates the traditional purification. The polymer can be removed quantitatively and it can be regenerated and reused for several cycles without losing its activity. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Copper‐Mediated One‐Pot Transformation of 2‐N‐Sulfonyl‐ aminoaryl Diselenides into Benzo[b][1,4]selenazines

A simple procedure for the one‐pot transformation of 2‐N‐tosylamino diselenides into benzo[b][1,4]selenazines has been established. The data collected indicate that the six‐membered heterocyclic ring is the result of a [4+2] cycloaddition reaction of a transient electron‐poor o‐iminoselenoquinone, acting as diene, with an electron‐rich alkene, performing as dienophile. The key step of the synthesis is a 1,4‐elimination at selenium of a selenolate ion, leading to the generation of the heterodiene, that requires catalytic amounts of copper(II) trifluoromethanesulfonate, for the activation of the selenium‐selenium bond.     

Synthesis of 3‐Arylindole‐2‐carboxylates via Copper‐Catalyzed Hydroarylation of o‐Nitrophenyl‐Substituted Alkynoates and Subsequent Cadogan Cyclization

A two‐step route to biologically important 3‐arylindole‐2‐carboxylic esters has been successfully established: o‐nitrophenyl‐substituted alkynoates underwent copper‐catalyzed hydroarylation in the presence of commercially available arylboronic acids to afford 3,3‐diarylacrylates, which were then converted to indolecarboxylates via a modified Cadogan cyclization using a molybdenum catalyst and triphenylphosphine.     

Copper‐Catalyzed Three‐Component Synthesis of 2‐Iminodihydrocoumarins and 2‐Iminocoumarins

An efficient synthesis of N‐sulfonyl‐substituted 2‐imino‐3,4‐dihydrocoumarins and 2‐iminocoumarins via a copper‐catalyzed multicomponent reaction of sulfonyl azides with terminal alkynes and β‐(ortho‐hydroxyphenyl)‐α,β‐unsaturated ketones or ortho‐hydroxyphenylpropiolates has been developed. The cascade process involves trapping the keteimine by a nucleophilic addition and an intramolecular Michael addition. This methodology could well be extended to the concise synthesis of the polysubstituted piperidine scaffold.     

A Rhodium‐Catalyzed Cascade Cyclization: Direct Synthesis of N‐Substituted Phthalimides from Isocyanates and Benzoic Acids

A rhodium(III)‐catalyzed amidation between benzoic acids and isocyanates via direct functionalization of an ortho C H bond followed by intramolecular cyclization is described. This cascade cyclization affords N‐substituted phthalimides in one step in 26–91% yields. The reaction is highly atom‐economical, since no theoretical waste except for water is generated in the reaction.

     

Enantioselective Organocatalytic Synthesis of Arylglycines via Friedel–Crafts Alkylation of Arenes with a Glyoxylate Imine

The enantioselective organocatalytic synthesis of arylglycines has been developed employing 1 mol% of an enantiopure N‐triflyl phosphoramide Brønsted acid as organocatalyst. Various differently substituted phenylglycine derivatives can be synthesized in good to excellent yields and enantiomeric excesses based on a Friedel–Crafts alkylation of electron‐rich arenes with a glyoxylate imine. A novel protocol for the deprotection of the N‐tert‐butylsulfonyl (Bus) group has also been developed.     

Synthesis of Natural Tea‐Saponin‐Based Succinic Acid Sulfonate as Anionic Foaming Agent

Tea saponin (TS) is a relatively inexpensive natural nonionic surfactant extracted from parts of tea plants, which can be modified into an anionic surfactant to achieve better surface activity. In this paper, the synthesis of TS‐based succinic acid sulfonate as an anionic foaming agent is described. TS used as the hydrophobic source was modified by maleic anhydride (MAH) and then reacted with sodium bisulfite. Orthogonal experiment of a 2‐step reaction was designed and performed, resulting in 9 kinds of succinic acid tea‐saponin sulfonate (STS). 4‐Dimethylaminopyridine and tetrabutylammonium bromide were, respectively, used as catalyst for the esterification with MAH and the sulfonation with sodium bisulfite. During the synthesis process, N,N‐dimethylformamide was employed as the solvent and ethyl acetate as the extractant. The molecular structure of STS was confirmed by infrared spectroscopy and mass spectrometry. The foaming property of STS was investigated through comparison with different kinds of common surfactants. The results show great prospects of these environmentally friendly anionic surfactants.     

Stoichiometric Reductive C?N Bond Formation of Arylgold(III) Complexes with N‐Nucleophiles

The reductive formation of substituted anilines from amines and three well‐defined aryl‐ gold(III) complexes, i.e., dichloro(2,6‐lutidine)phen‐ ylgold(III) ( 2 ), dichloro(2,6‐lutidine)‐p‐tolylgold(III) ( 3 ), and chlorobis(triphenylphosphine)phenylgold(III) chloride ( 4 ) was studied. The reaction is stoichiometric in gold and represents a key step of a potential gold‐catalyzed intermolecular amination reaction of arenes. It proceeds smoothly with a broad range of N‐nucleophiles in the presence of sodium acetate (NaOAc) and enables the selective formation of N‐substituted anilines in good yields. A mechanistic pathway is proposed and discussed as well.     

Quinone‐Fused Pyrazoles through 1,3‐Dipolar Cycloadditions: Synthesis of Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma Cancer Cells

A novel and straightforward synthesis of highly substituted isoquinoline‐5,8‐dione fused tricyclic pyrazoles is reported. The key step of the synthetic sequence is a regioselective, Ag₂CO₃ promoted, 1,3‐dipolar cycloaddition of C‐heteroaryl‐N‐aryl nitrilimines and substituted isoquinoline‐5,8‐diones. The broad functional group tolerability and mild reaction conditions were found to be suitable for the preparation of a small library of compounds. These scaffolds were designed to interact with multiple biological residues, and two of them, after brief synthetic elaborations, were analyzed by molecular docking studies as potential anticancer drugs. In vitro studies confirmed the potent anticancer effects, showing promising IC₅₀ values as low as 2.5 μm against three different glioblastoma cell lines. Their cytotoxic activity was finally positively correlated to their ability to inhibit PI3K/mTOR kinases, which are responsible for the regulation of diverse cellular processes in human cancer cells.     

Direct polymer reaction of poly(styrene‐co‐maleic anhydride): Polymeric imidization

Using direct polymer reaction of poly(styrene‐co‐maleic anhydride) (SMA), a synthesis of copolymer of styrene and N‐aryl succinimide (SMI) has been investigated. SMI copolymers were synthesized from SMA copolymers by a concerted two‐step reaction, which consisted of the condensation reaction (step 1) of SMA with aromatic amine to prepare a precursor, succinamic acid, for imide formation and the cyclodehydration reaction (step 2) of succinamic acid. In this article, the application of Searle's preparation method of N‐aryl or N‐alkyl maleimide to the direct polymer reaction for SMI was attempted. Compared with synthesis of monomeric imides, the imide formation in polymeric condition appeared to be a little more sensitive to the reaction condition. The optimum condition for maximum conversion was examined in terms of time, temperature, and the amount of reactants. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 1187–1196, 1999     

Iron‐Catalyzed Amidation of Aldehydes with N‐Chloroamines

A new direct conversion of aldehydes to amides has been realized, in the presence of iron(III) chloride as a catalyst and using tert‐butyl hydroperoxide (TBHP) as an oxidant. Both aliphatic and aromatic aldehydes were successfully reacted with variously mono‐ and di‐substituted N‐chloroamines. The methodology has a wide substrate scope, uses cheap and easily available reagents and is characterized by short reaction times.     

Synthesis and characterization of a new diol‐functionalized s‐triazine‐based polymerizable hindered amine light stabilizer

A new diol‐functionalized triazine‐based polymerizable hindered amine light stabilizer (HALS) was synthesized in two steps. First, selective synthesis of an s‐triazine containing two HALS moieties as substituents was accomplished by using phase‐transfer catalysis. This step required the establishment of optimum reaction conditions (type of two‐phase system, best solvent, and catalyst). In the second step, the substituted triazine was treated with diethanolamine to introduce polymerizable diol functionality. The resulting product should act as a light stabilizer, since it contains two HALS moieties anchored to a thermally stable s‐triazine unit. Moreover, incorporation of the diol into a polymeric material might be expected to impart prolonged stability in weathering environments. Characterization of the diol was accomplished by using Fourier transform infrared spectroscopy (FTIR), 'H NMR, and mass spectrometry. J. VINYL ADDIT. TECHNOL., 18:204–208, 2012. © 2012 Society of Plastics Engineers