Efficient Transamidation Research Articles

Metal- and Hazardous Reagent-Free Transamidation Process: the NH2OH⦁HCl Promoted N-Formylation and N-Acylation Reaction under Solvent-Less Conditions

An efficient transamidation process has been described under solvent-less conditions. The transformation has been accomplished by employing NH2OH⦁HCl as a reagent and amines as substrates. The developed method is achieved in the absence of metals and hazardous reagents. A series of amines were explored to obtain the N-formylation and N-acylation reactions with excellent yields (81-96%) of products. The DFT analysis was also performed, which provides a clear understanding of the described N-formylation process. The postulated mechanism is well supported by the control experiments.

Design and Evolution of Enhanced Peptide-Peptide Ligation for Modular Transglutaminase Assembly.

Robust and precise tools are needed to enhance the functionality and resilience of synthetic nanoarchitectures. Here, we have employed directed evolution and rational design to build a fast-acting molecular superglue from a bacterial adhesion protein. We have generated the SnoopLigase2 coupling system, a genetically encoded route for efficient transamidation between SnoopTag2 and DogTag2 peptides. Each peptide was selected for rapid reaction by phage display screening. The optimized set allows more than 99% completion and is compatible with diverse buffers, pH values, and temperatures, accelerating the reaction over 1000-fold. SnoopLigase2 directs a specific reaction in the mammalian secretory pathway, allowing covalent display on the plasma membrane. Transglutaminase 2 (TG2) has a network of interactions and substrates amidst the mammalian cell surface and extracellular matrix. We expressed a modified TG2 with resistance to oxidative inactivation and minimal self-reactivity. SnoopLigase2 enables TG2 functionalization with transforming growth factor alpha (TGFα) in routes that would be impossible through genetic fusion. The TG2:TGFα conjugate retained transamidase activity, stably anchored TGFα for signal activation in the extracellular environment, and reprogrammed cell behavior. This modular toolbox should create new opportunities for molecular assembly, both for novel biomaterials and complex cellular environments.

Zinc-catalyzed transamidation and esterification of N-benzoyl cytosine via C-N bond cleavage.

We have utilized N-benzoyl cytosine for efficient transamidation and esterification via catalytic C-N bond cleavage. The one-pot strategy involves the reaction of secondary amide with various aliphatic or aromatic amines and alcohols in the presence of zinc triflate and DTBP, affording diverse amides and esters in excellent yields.

Solvent-free, Efficient Transamidation of Carboxamides with Amines Catalyzed by Recyclable Sulfated Polyborate Catalyst

Transamidation is a significant reaction in organic and medicinal chemistry. The amide is one of the most important functional groups used in organic transformations, and it is found in a wide vari...

Mesoporous silica nanoparticles in an efficient solvent-free transamidation of carboxamides with amines: an exhibition of a green recyclable nanocatalyst

A protocol is described for an efficient transamidation of amides with amines in the presence of mesoporous silica nanoparticles (MSNs). The latter is used as a green, heterogeneous, and recyclable nanocatalyst, under solvent-free conditions. Following this protocol, a wide range of aromatic, aliphatic, and cyclic/acyclic primary or secondary amines are used in synthesis of a series of amides with good to excellent yields (65–96%). MSNs is characterized by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), small-angle powder X-ray diffraction (XRD), nitrogen adsorption-desorption analysis, and FT-IR spectroscopy. The metal/solvent-free condition, easy work up, high purity of the products, recyclability, and environmentally-friendly nature of the catalyst are the attractive features of this methodology.

Guanidine Acetic Acid Functionalized Magnetic Nanoparticles: Recoverable Green Catalyst for Transamidation

AbstractIn the presence of a catalytic amount of Fe3O4‐Guanidine acetic acid (GAA) nanoparticles, efficient transamidation of several amides with various amines is described under solvent‐free conditions. Fe3O4‐Guanidine acetic acid nanoparticles provide the first example of a magnetically recoverable organocatalyst for transamidation in the highest catalytic activity. The catalyst could be simply recycled with the assistance of an external magnet and reused for six runs without significant loss of its catalytic activity.

High‐temperature copolyamides obtained by the efficient transamidation of crystalline–crystalline polyamide blends

ABSTRACTHigh‐performance thermoplastic composites based on semiaromatic polyamides are prime candidates for metal replacement in lightweight structural applications. However, the low ductility and toughness of semiaromatic polyamides remain major obstacles to their wider industrial application. In this study, we showed that novel random copolymers were formed by the unexpectedly efficient transamidation during the melt compounding of semicrystalline semiaromatic and aliphatic polyamides. Thus, homogeneous materials with a single glass transition and a high degree of crystalline order were obtained from blends of the semiaromatic poly(hexamethylene terephthalamide‐co‐isophthalamide) (PA6TI) with poly(hexamethylene adipamide) (PA66) or poly(hexamethylene sebacoamide) (PA610). By contrast, phase segregation and a less efficient transamidation was observed for cocompounded PA6TI and polylaurolactam (PA12). We attributed this to differences in the hydrogen‐bonding patterns of the two polyamides. This study opened the way for the preparation of novel high‐performance thermoplastic polyamides and composites through simple melt compounding. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44349.

ChemInform Abstract: Synthesis of N‐Arylcarboxamides by the Efficient Transamidation of DMF and Derivatives with Anilines.

AbstractThe scalable reaction tolerates a broad range of functional groups.

Transamidation of primary carboxamides, phthalimide, urea and thiourea with amines using Fe(OH)3@Fe3O4 magnetic nanoparticles as an efficient recyclable catalyst

The highly efficient transamidation of primary amides, phthalimide, urea and thiourea with amines catalyzed by magnetic Fe3O4@Fe(OH)3 nanoparticles is described.

Synthesis of N-arylcarboxamides by the efficient transamidation of DMF and derivatives with anilines

A novel protocol for the transamidation of DMF and derivatives with weakly nucleophilic anilines has been developed, utilizing a catalytic amount of Pd(OAc)2 and 2,2′-bipyridine, and with PivOH and BF3·Et2O as additives. This methodology has a broad substrate scope, and various corresponding transamidation products were prepared in good to excellent yields from commercially available DMF derivatives and anilines. The synthetic utility of the reported protocol was further demonstrated with a gram-scale experiment. Control experiments suggested the efficient transformation of DMF and derivatives with anilines might owe to the synergistic effect of palladium complex, PivOH, and BF3·Et2O.

H-β-zeolite catalyzed transamidation of carboxamides, phthalimide, formamides and thioamides with amines under neat conditions

Efficient transamidation of unactivated carboxamides, phthalimides, formamides and thioamides with amines under solvent-free conditions using H-β-zeolite as a green and recyclable heterogeneous catalyst is described.

ChemInform Abstract: Transamidation of Carboxamides Catalyzed by Fe(III) and Water.

AbstractA highly efficient transamidation method is presented for several primary, secondary, and tertiary amides with aliphatic and aromatic amines (primary and secondary).

Transamidation of carboxamides catalyzed by Fe(III) and water.

The highly efficient transamidation of several primary, secondary, and tertiary amides with aliphatic and aromatic amines (primary and secondary) is described. The reaction is performed in the presence of a 5 mol % concentration of different hydrated salts of Fe(III), and the results show that the presence of water is crucial. The methodology was also applied to urea and phthalimide to demonstrate its versatility and wide substrate scope. An example of its use is an intramolecular application in the synthesis of 2,3-dihydro-5H-benzo[b]-1,4-thiazepin-4-one, which is the bicyclic core of diltiazem and structurally related drugs (Budriesi, R.; Cosimelli, B.; Ioan, P.; Carosati, E.; Ugenti, M. P.; Spisani, R. Curr. Med. Chem. 2007, 14, 279-287). A plausible mechanism that explains the role of water is proposed on the basis of experimental observations and previous mechanistic suggestions for transamidation reactions catalyzed by transition metals such as copper and aluminum. This methodology represents a significant improvement over other existing methods; it can be performed in air and with wet or technical grade solvents.

Hypervalent iodine catalyzed transamidation of carboxamides with amines

This protocol describes the catalytic use of diacetoxyiodobenzene (DIB) for the efficient transamidation of carboxamides with amines under mild conditions.

Efficient Transamidation of Primary Carboxamides by in situ Activation with N,N‐Dialkylformamide Dimethyl Acetals.

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.

Efficient Transamidation of Primary Carboxamides by in Situ Activation with N,N-Dialkylformamide Dimethyl Acetals

Two protocols for the transamidation of primary amides with primary and secondary amines, forming secondary and tertiary amides, respectively, are described. Both processes employ N,N-dialkylformamide dimethyl acetals for primary amide activation, producing N'-acyl-N,N-dialkylformamidines as intermediates, as widely documented in the literature. Although the latter intermediates react irreversibly with amines by amidinyl transfer, we show that in the presence of certain Lewis acid additives efficient acyl transfer occurs, providing new and useful methods for amide exchange. In one protocol for transamidation, the N'-acyl-N,N-dialkylformamidine intermediates are purified by flash-column chromatography and the purified intermediates are then treated with an amine (typically, 2.5 equiv) in the presence of scandium triflate (10 mol %) in ether to form in high yields the products of transamidation. In a second procedure, N'-acyl-N,N-dialkylformamidines are generated in situ and, without isolation, are subjected to transamidation in the presence of zirconium chloride (0.5 equiv) and an amine (typically 2 equiv). A variety of different primary amides and amines are found to undergo efficient transamidation using the methods described.

Synthesis and antifungal activity of 1,3,2-benzodithiazole S-oxides.

The preparation of 1,3,2-benzodithiazole S-oxide analogs exhibiting in vitro antifungal activity against several strains of Candida is described. For the preparation of derivatives bearing aromatic substituents, a novel electrophilic aromatic thiolation reaction was utilized which produced substituted aromatic 1,2-dithiol intermediates. The reactions of nucleophiles with the parent heterocyclic system have led to an efficient transamidation process which allows for the direct production of these analogs. The S-oxide bond exhibits poor stereochemical stability and has been found to epimerize under ambient conditions. The structure-activity data report that a side chain of greater than 10 carbons effects a loss in activity as does the placement of polar groups in this chain.