Acylation Of Amines Research Articles

Immobilized lipase YlLip2-catalyzed resolution of (±)α-phenylethyl amine in a medium with organic cosolvent

In this paper, we studied the enantioselective aminolysis activity of an immobilized extracellular lipase LIP2 (YlLip2) from Yarrowia lipolytica by catalyzing enantioselective acylation of (±)α-phenylethyl amine with acetic ester in a medium containing cosolvent. The reaction parameters including cosolvent concentration, reaction temperature, amount of the immobilized lipase and the reaction time were optimized. When the reaction was carried out in hexane with the presence of 3% DMSO and six pieces of immobilized lipase at 45 °C for 6 days, the enantiomeric excess of product ( e.e.p) markedly increased from 0.35 (in neat hexane) to 0.96 and the enantiomeric ratio ( E) improved from 2.5 (in neat hexane) to 190. The immobilized lipase could be reused at least five consecutive batches at high E (≈190).

A one-pot, two-step microwave-assisted synthesis of highly functionalized benzoxazoles using solid-supported reagents (SSRs)

A one-pot, two-step protocol for the microwave-assisted solid-phase synthesis of substituted benzoxazoles has been developed starting from different polymer-bound esters we previously designed as solid-supported reagents (SSRs) for the acylation of amines, alcohols and phenols. The combination of a parallel synthesizer and a microwave reactor allowed to quickly prepare a collection of substituted benzoxaxoles in high purity and satisfactory yields. This protocol is amenable for automation and could be used for the preparation of combinatorial libraries in drug discovery programs.

SbCl3 as a Highly Efficient Catalyst for the Acetylation of Alcohols, Phenols, and Amines under Solvent‐Free Conditions

Antimony trichloride has been found to be an efficient and expedient catalyst for the acylation of alcohols, phenols, amines, and sugars with acetic anhydride in high yields and in a short reaction time under solvent‐free conditions at room temperature. Also, racemization of chiral alcohols and epimerization of sugars were not observed in any of the substrates.

Enzyme-Like Chemoselective Acylation of Alcohols in the Presence of Amines Catalyzed by a Tetranuclear Zinc Cluster

Acylation of alcohols and amines is one of the most fundamental reactions. Due to the greater nucleophilicity of the amino group compared to the hydroxyl group, complete N-acylation occurs. Only an enzymatic reaction can promote a highly selective O-acylation reaction, and there are no examples using an artificial catalyst. Here we report that the tetranuclear zinc cluster Zn4(OCOCF3)6O efficiently catalyzes highly chemoselective O-acylation in the presence of primary and secondary alkyl amines. Our results suggest the high potential of the zinc cluster as the core structure of an artificial enzyme to realize further enzyme-like chemoselective reactions.

ChemInform Abstract: SO42‐/SnO2: Efficient, Chemoselective, and Reusable Catalyst for Acylation of Alcohols, Phenols, and Amines at Room Temperature.

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A green, fully enzymatic procedure for amine resolution, using a lipase and a penicillin G acylase

A green procedure for the kinetic resolution of chiral amines via enzymatic acylation and deacylation has been demonstrated. The fully enzymatic approach obviates the common, waste-generating deacylation under strongly alkaline conditions. The acylating agent was (R)-phenylglycine propyl ester in combination with Candida antarctica lipase B as acylation catalyst. The enantiomerically enriched amides were subsequently deacylated in the presence of the penicillin G acylase from Alcaligenes faecalis. The degree of enantiomer recognition by CaLB in the acylation of aliphatic amines was unexpectedly modest, but a considerable further enantiomeric enrichment could be accomplished in the course of the subsequent enzymatic hydrolysis step.

Selective Acylation of Primary Amines in Peptides and Proteins

N-hydroxysuccinimide (NHS) esters are derivatizing agents that target primary amine groups. However, even a small molar excess of NHS may lead to acylation of hydroxyl-containing amino acids as a side reaction. We report a straightforward method for the selective removal of ester-linked acyl groups after NHS ester-mediated acylation of peptides and proteins. It is based on incubation in a boiling water bath and does not require a change in pH or the addition of chemicals. It is therefore particularly suited for proteomics samples that are often small in volume and contain low amounts of peptides. The method was optimized and evaluated with two peptides and one protein that were acetylated at a high excess of NHS-acetate. While the large molar excess resulted in complete acylation of all primary amines, hydroxyl-containing amino acids were shown to react as well. By incubating the peptide or protein solutions in a boiling water bath, acetyl-ester bonds were hydrolyzed, whereas acetyl-amide bonds remained stable. The reaction was also performed in 6 M guanidine-HCl, which prevented protein precipitation. In conclusion, the present method allows the selective acylation of primary amines by NHS esters and constitutes a valuable alternative to the treatment with hydroxylamine under alkaline conditions.

SO4 2−/SnO2: Efficient, Chemoselective, and Reusable Catalyst for Acylation of Alcohols, Phenols, and Amines at Room Temperature

SO4 2−/SnO2 was employed for the acylation of a variety of alcohols, phenols, and amines under solvent‐free conditions at room temperature. This method showed preferential selectivity for acetylation of the amino group in the presence of a hydroxyl group. The reported method is simple, mild, and environmentally viable, using several other acid anhydrides at room temperature.

A Simple and Mild Acylation of Alcohols, Phenols, Amines, and Thiols with a Reusable Heteropoly Acid Catalyst (H6P2W18O62·24 H2O)

The acylation of alcohols, phenols, thiols, and amines with varied substitution using acid anhydrides is efficiently catalyzed by Wells‐Dawson heteropoly acid (H6P2W18O62·24 H2O). Reactions proceed with very good to excellent yield in air at room temperature, using toluene as solvent (40 examples). The bulk catalyst was easily reused without appreciable loss of its activity.

Helical conformation of the copolymers of l-proline derivatives based propargylether and chiral N-propargylamide

The novel acetylene monomers, l-proline derivatives based propargylethers PR (PA, PC, and PL) were synthesized by alkylation of Boc-hydroxyproline with propargyl bromide and acylation of achiral amine. The homopolymers of the novel acetylene monomer exist in no regulated higher order structure in solvents because of the lack of hydrogen bond and the unique ring structure in the pendant. Consequently, the copolymerization of l-proline-derived chiral propargylether PR with the l-alanine-derived N-propargylamide (LA) was formed and the chiroptical properties of the formed copolymers were examined. We conclude that (1) N–H of the amide group at 2-position in proline play an important role in the formation of helical conformation of poly(LA88-co-PR12); (2) improving the amount of PC of poly(LA-co-PC) changes the conformation of the copolymer in CHCl3 and perturbs the leadership of LA; (3) the conformation of poly(LA75-co-PC25) remarkably changes with changing temperature and PC obtains the leadership in the competition on the conformation of poly(LA75-co-PC25) in CHCl3 with the improvement of temperature.

Sulphated zirconia catalyzed acylation of phenols, alcohols and amines under solvent free conditions

Sulphated zirconia prepared by the treatment of a high surface area zirconia (320 m 2 g −1) with 1 N H 2SO 4 shows a strong acidity after calcination at 893 K. It is comparable to that of zeolites, with an enthalpy of adsorption of NH 3 close to 130 kJ mol −1. The isotherm of N 2 adsorption at 77 K on the sulphated zirconia shows characteristic of mesoporous solid having surface area about 125 m 2 g −1, and pores of 4 nm as determined applying the BJH method. The sulphated zirconia obtained by sulphation has 14.5 wt.% S just after oven drying and 1.8 wt.% S after calcination at 893 K. The X-ray diffraction pattern of the calcined sample shows the presence of an intensive peak at 2 θ = 30 characteristic of the tetragonal structure. This solid acid has been applied to the acylation of a variety of phenols, alcohols and amines with acetic anhydride as an acylating agent under solvent free conditions. The yields reach about 95% in 10 min, and the catalyst can be recycled several times, so that this process could find useful applications.

Metal-triflate ionic liquid systems immobilized onto mesoporous MS41 materials as new and efficient catalysts for N-acylation

Two kinds of MS41-immobilized ionic liquids (ILs) based on dihydroimidazolium and pyridinium cation were prepared using a grafting method. The second immobilization of triflate salts on these materials led to the immobilization of metal-triflate complexes into ILs. The materials thus obtained were characterized by 1H NMR, XRD, N2-sorption measurements, TG–DTA, DRIFT, XPS, TEM, and ICP-AES. The catalysts were tested in acylation of amines and sulfonamides and proved highly active and selective. For both aromatic and aliphatic amines, acylation with carboxylic acids was possible. For sulfonamides, acylation was possible only with anhydrides. Recycling the catalysts was not accompanied by any leaching of ILs or metal triflate.

Application of N-halo reagents in organic synthesis

This review article summarizes published data on the application of N-halo reagents (such as N-halo amines, N-halo amides and/or imides, N-halo sulfonamides and/or imides, and etc.) in various organic functional group transformations such as: oxidation reactions, deprotection and protection of different functional groups, halogenation of saturated and unsaturated compounds, acylation of alcohols, phenols, amines or thiols, epoxidation of alkenes, aziridination and etc. The main purpose of writing this review is encouraging of active researchers interested to this field for the synthesis of new N-halo reagents specially with different halogens and applications of these new N-halo reagents in organic reactions or finding more and more applications of existing N-halo reagents in organic synthesis.

Efficient Amidation from Carboxylic Acids and Azides via Selenocarboxylates: Application to the Coupling of Amino Acids and Peptides with Azides

A facile one-pot procedure for the coupling of carboxylic acid and azide via selenocarboxylate and selenatriazoline has been developed and successfully applied to the coupling of amino acids and peptides with azides. Selenocarboxylates are readily prepared by the reaction of the activated carboxylic acids with LiAlHSeH under mild conditions. The selenocarboxylates formed in situ are used to react directly with azides to form the corresponding amides via a selenatriazoline intermediate. Excellent yields were obtained for electron-deficient azides, and moderate to good yields were obtained for electron-rich azides. The selenocarboxylate/azide amidation reaction is clean and chemoselective. It provides an attractive alternative method to the conventional acylation of amines when an amide bond needs to be formed without going through an amine intermediate.

Supramolecular PEG−co-Oligo(p-benzamide)s Prepared on a Peptide Synthesizer

An automated synthesis protocol has been developed for the preparation of oligo(p-benzamide)s on solid support using a commercial peptide synthesizer employing a variation of standard Fmoc chemistry. Bis(trichloromethyl carbonate) in NMP was used to activate the aromatic carboxylic acids for acylation of secondary aromatic amines on solid support. N-Protected hepta(p-benzamide) was automatically prepared on solid support and manually converted to a solid supported block co-oligomer by attaching a poly(ethylene glycol) chain. Cleavage from the support could be achieved with minimal loss of the p-methoxybenzyl N-protective group. While the N-protected block co-oligomer was molecularly dissolved in nonpolar organic solvents, the N-deprotected block co-oligomer adopted a rod-coil conformation and showed strong aggregation as evidenced by gel permeation chromatography and transmission electron microscopy. Rigid rodlike aggregates could be observed in chloroform, toluene, as well as water.

Catalytic transesterification of crude rapeseed oil by liquid organic amine and co-catalyst in supercritical methanol

Liquid organic amines, Ethylenediamine (EDA), Diethylamine (DEA) or Triethylamine (TEA), could speed up the production of methyl ester from crude rapeseed oil in supercritical methanol. The order of the catalytic activity was EDA > DEA > TEA. Acyl amine appeared in the products when EDA or DEA was used as the catalyst; however, this phenomenon didn’t occur when TEA was used. With Propylene oxide as the co-catalyst, the catalytic activity of TEA was greatly improved. In 10 min, the yield of methyl ester could reach 89.5%, which was seven times faster than that without the co-catalyst. Optimum molar ratio of methanol to crude rapeseed oil should not be lower than 24:1.

Additive-Free Chemoselective Acylation of Amines and Thiols

Amines with different stereoelectronic nature were efficiently acylated at room temperature using acetic anhydride in the presence of no solvent or additive. Various thiols also react equally well under the same conditions. Chemoselective protection of amines in the presence of thiols, alcohols, and phenols and of thiols in the presence of alcohols, and phenols were achieved using competitive experiments.

1,3‐Dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐one.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Thiophene Backbone Amide Linkers, a New Class of Easily Prepared and Highly Acid-Labile Linkers for Solid-Phase Synthesis

Solid-phase synthesis is of tremendous importance for small-molecule and biopolymer synthesis. Linkers (handles) that release amide-containing products after completion of solid-phase synthesis are widely used. Here we present a new class of highly acid-labile backbone amide linkers (BAL handles) based on 3,4-ethylenedioxythiophene (EDOT), which we have termed T-BAL. These thiophene linkers are synthesized in three convenient steps from commercially available EDOT. In the linker design, the spacer was introduced to the EDOT core either via a carbon-carbon bond or via a thioether linkage. Introduction of the spacer via a C-C bond was performed by a chemoselective Negishi coupling without transient protection of the aldehyde group to provide the T-BAL1 handle. Introduction via a thioether linkage was performed by a facile nucleophilic aromatic substitution between the brominated EDOT aldehyde and unprotected mercapto acids to provide T-BAL2 and T-BAL3 handles. The minimal use of protecting groups gave the corresponding linker molecules in few synthetic steps and in good yields. After anchoring of the linker to a polymeric support, introduction of the first amino acid was achieved by reductive amination, giving a secondary amine. A following acylation of the secondary amine with a symmetrical amino acid anhydride resulted in a backbone amide linkage between the handle and the growing substrate (e.g., peptide chain). After solid-phase synthesis, the substrates could be released from the resin by either low acid conditions using 1% TFA in CH2Cl2 or high acid conditions such as 50% TFA in CH2Cl2. Peptide thioesters could be released from the T-BAL1 handle under very mild conditions using aqueous acetic acid. Tert-butyl based protecting groups, tert-butyl esters, tert-butyl ethers, and Boc groups, as well as dimethyl acetals were relatively stable to these mild conditions for release of the peptides.

Zeolite Catalyzed Acylation of Alcohols and Amines with Acetic Acid under Microwave Irradiation.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.