Cross‐Coupling of Secondary Amides with Tertiary Amides: The Use of Tertiary Amides as Surrogates of Alkyl Carbanions for Ketone Synthesis

In recent years, exciting progress has been made in the field of direct transformation of amides, nevertheless, the condensation between two amides remains rare and restricted to homo‐coupling reactions. Herein, we report the cross‐coupling of secondary amides with tertiary amides, which provides a synthesis of ketones under mild conditions, and features the use of tertiary amides as surrogates of alkyl carbanions. The method relies on the coupling of enamines, generated from tertiary amides by catalytic partial reduction of tertiary amides with Vaska's catalyst, with nitrilium ions, formed in situ from secondary amides via activation with trifluoromethanesulfonic anhydride, and on the subsequent deformylation.     

Self-assembly driven by an aromatic primary amide motif

Primary amides are unique supramolecular synthons possessing two hydrogen donors and two hydrogen acceptors. By interacting in a complementary fashion, primary amides reliably generate two-dimensional hydrogen bonded networks that differ from conventional hydrogen bonded structures such as carboxylic acid dimers or one-dimensional secondary amide chains. This feature permits the design of sophisticated supramolecular assemblies based on primary amides (especially aromatic amides). Several interesting crystal structures have been constructed utilizing primary amides, although such structures have been applied only in the field of crystal engineering because the networks strongly favor crystallization. Expansion of the applications of primary amides to liquid crystals and self-assembly in solution requires an appropriate balance between primary amide-based hydrogen bonding and other noncovalent interactions. This perspective article reviews the key hydrogen bonding properties of primary amides determined from crystal structure studies, and a variety of supramolecular assemblies involving primary amides are discussed. A new strategy for overcoming crystallinity and solubility issues is proposed, involving introduction of a trifluoromethyl group at the ortho position of the aromatic primary amide. Such substitutions produce highly processable primary amides, while maintaining the two-dimensional hydrogen bonded network. Examples of self-assembly using 2-trifluoromethylbenzamide demonstrate its usefulness in self-assembly.     

Electrospray ionization mass spectra of monoimidazole/polyamine conjugates

Imidazole/polyamine amides are biologically important molecules due to their specific DNA binding activity, and much attention has been attracted to the synthesis of their derivatives or analogues. In the present studies, the fragmentation of a series of synthetic monoimidazole/polyamine amides was investigated using electrospray ionization mass spectrometry (ESI-MS) combined with tandem mass spectrometry (ESI-MS/MS). All of the monoimidazole/polyamine amides produced the fragment ion m/z 183 except for the monoimidazole/ethyldiamine amide. The diamine amides produced this ion after the elimination of an alkene, the triamine amides produced it via their corresponding diamine amide fragments, and the tetraamine amide via its triamine and then diamine amide fragments. The characterization of the mass spectra for the different polyamine amides allowed identification of a specific product from the N-acylation of spermidine, and should assist further study of the polyamine amides in DNA binding action.     

酰胺水化作用的富里埃红外光谱研究及其SCFPPP计算

本文用富里埃红外光谱仪研究了酰胺水化作用引起的红外光谱变化。用SCFPPP方法对五种酰胺进行了计算。含水酰胺的羰基伸缩振动频率向低波数的位移与酰胺和水分子间的氢键强度成正比。其氢键强度与羰基上氧原子的净电荷密度成正比,与酰胺分子的HOMO轨道能量成反比。     

Metal Amides as the Simplest Acid/Base Catalysts for Stereoselective Carbon–Carbon Bond‐Forming Reactions

In this paper, new possibilities for metal amides are described. Although typical metal amides are recognized as strong stoichiometric bases for deprotonation of inert or less acidic hydrogen atoms, transition‐metal amides, namely silver and copper amides, show interesting abilities as one of the simplest acid/base catalysts in stereoselective carbon–carbon bond‐forming reactions.     

Product Control using Substrate Design: Ruthenium‐Catalysed Oxidative C−H Olefinations of Cyclic Weinreb Amides

A new class of Weinreb amides has been developed as directing groups for the ruthenium‐catalysed regioselective oxidative C?H olefination. The new Weinreb amides successfully inhibit the N?O bond reductive cleavage usually associated with the cationic ruthenium system, thereby keeping intact the synthetic utility of Weinreb amides. Mechanistic studies reveal interesting aspects of the directing group capabilities of Weinreb amides when compared to simple amides of similar structures.     

Rapid structural determination of amides in Piper longum by high-performance liquid chromatography combined with ion trap mass spectrometry

A reversed-phase liquid chromatography/tandem multistage mass spectrometry (MS/MS) method was developed for the characterization of amides from the extracts of Piper longum. The characteristic fragmentations of the amides found in P. longum showed diagnostic structural information. Extracted ion chromatography (EIC) and constant neutral losses were used to guide the search for the amides of interest. Amides of known structures that contain four subtypes of amides were rapidly determined, and novel amides were also identified for this plant. Forty-two amides were rapidly identified, of which 22 were found in this plant for the first time and 9 were new compounds. The method is convenient and sensitive, especially for minor components in the unpurified, complex mixture; the structures of unknown constituents could be determined, in the absence of authentic sample, by comparison of the fragmentation patterns with those of homologous compounds.     

不对称芳基取代的方酰胺和异方酰胺的合成

Ｎ－芳基氮氧方酸的活性羟基能够被芳伯胺取代。利用这一特性，可在方酸四碳环上引入另一不同的芳胺基，即可获得不对称芳基取代的方酰胺或异方酰胺。以乙醇等为介质，芳伯胺与７种Ｎ－芳基氮方酸反应，制得２５个不对称的方酰胺和２４个不对称的异方酰胺。该合成方法优点突出，反应简便有效，通用性强。     

Polyunsaturated alkyl amides from Echinacea: synthesis of diynes, enynes, and dienes

The synthesis of 20 alkyl amides, including 15 naturally occurring polyunsaturated alkyl amides previously identified from Echinacea spp. (1-13 and 62) or from Achilla sp. (55) and five previously unknown geometric isomers (23, 28, 67, 73, and 80), is described. Importantly, these amides include all of the major alkyl amides present in commercially used Echinacea extracts. The syntheses demonstrate methodology used for constructing alkyl amides containing conjugated diyne and isomerically pure enyne and diene moieties and may be adapted easily for the preparation of other alkyl amides present in Echinacea spp. Terminal-conjugated diynes were prepared by a Cadiot-Chodkiewitz coupling/deprotection sequence utilizing a protected bromoacetylene, and methyl-substituted diynes were made via a base-catalyzed rearrangement of terminal-skipped diynes. Conjugated dienes were prepared conveniently and with high stereoselectivity by the reduction of enynes or diynes with Rieke zinc. With the exception of 1-2 and 11-12, the alkyl amides are synthesized here for the first time, and their NMR data are consistent with that of the reported isolated natural compounds.     

Nematocidal activity of long alkyl chain amides, amines, and their derivatives on dog roundworm larvae.

The nematocidal activity of amides and amines having a long alkyl chain against the second-stage larva of dog roundworm, Toxocara canis, was examined. Long chain acyl amides with smaller substituents on the nitrogen showed stronger activity and the activity of cyclic amine amides was stronger than that of acyclic ones. In a series of homologous amides, the activity was dependent on the alkyl chain length: it reached a maximum at an optimal chain length and decreased in both shorter and longer homologues. The relationship between the activity and hydrophobicity of the homologues was analysed by the use of the bilinear model. The hydrophobicity of a compound, which gives a maximal activity, was similar for all neutral amides, but amides which have an additional amine group in the molecule had different values. Tertiary amines and their salts having a long alkyl chain also showed nematocidal activities comparable to those of the corresponding amides. The salts killed the larva at concentrations lower than their critical micell concentration, suggesting that they behave as a single molecule for the nematocidal action.     

A Photochemical Protocol for the Synthesis of Weinreb and Morpholine Amides from Carboxylic Acids

In recent years, the development of light-mediated methods for synthetic applications has attracted high interest, because such methods constitute alternative approaches for the production of valuable chemical products. We study herein a photochemical protocol for the synthesis of Weinreb amides and morpholine amides from carboxylic acids. Various carboxylic acids were directly coupled to N,O-dimethylhydroxylamine, upon irradiation with either LED 370 nm or sunlight in the presence of 4-dimethylaminopyridine and bromotrichloromethane, providing Weinreb amides in moderate to high yields. Similarly, morpholine amides were obtained in satisfactory to high yields under sunlight or LED 370 nm irradiation. Thus, the versatile building blocks Weinreb amides and morpholine amides may be efficiently synthesized directly from carboxylic acids by light-mediated approaches, without the need of coupling reagents or pre-activation of carboxylic acids.     

Palladium-catalyzed intermolecular alpha-arylation of zinc amide enolates under mild conditions

The intermolecular alpha-arylation and vinylation of amides by palladium-catalyzed coupling of aryl bromides and vinyl bromides with zinc enolates of amides is reported. Reactions of three different types of zinc enolates have been developed. The reactions of aryl halides occur in high yields with isolated Reformatsky reagents generated from alpha-bromo amides, with Reformatsky reagents generated in situ from alpha-bromo amides, and with zinc enolates generated by quenching lithium enolates of amides with zinc chloride. This use of zinc enolates, instead of alkali metal enolates, greatly expands the scope of amide arylation. The reactions occur at room temperature or 70 degrees C with bromoarenes containing cyano, nitro, ester, keto, fluoro, hydroxyl, or amino functionality and with bromopyridines. Moreover, the reaction has been developed with morpholine amides, the products of which are precursors to ketones and aldehydes. The arylation of zinc enolates of amides was conducted with catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) or the highly reactive, dimeric, Pd(I) complex [[P(t-Bu)3]PdBr]2.     

Synthesis of amides through the Cannizzaro-type reaction catalyzed by lanthanide chlorides

Amidation of aldehydes with lithium amides through the LnCl₃-catalyzed Cannizzaro-type reactions afforded a variety of amides in high yields. The electronic and steric effects on the reaction were investigated. The features of the economical catalysts, high yields, tolerance of a wide range of lithium amides and aromatic aldehydes make this methodology an easy and valid contribution to the direct synthesis of amides from aldehydes.     

Restricted rotation in amides. VII—methods of resonance assignment in tertiary amides—an evaluation

Examination and evaluation of various methods for resonance assignments in amides reveals that only three of these are reliable: (a) the nuclear Overhauser effect, which leads to unequivocal results in tertiary amides; (b) the aromatic solvent induced shift, which is rapid and accurate for tertiary amides without polar substituents; (c) the lanthanide-induced shift, which although easy, can be applied only to tertiary amides with substituents that do not complex lanthanides.     

Conquering amide planarity: Structural distortion and its hidden reactivity

Amides are generally considered as a low-reactive chemical entity among the carbonyl group, and therefore fewer opportunities to be involved in catalytic transformations as substrates. The origin of the stable nature of amides is resonance stabilization in the planar structure, which has drawn considerable attention from organic and physical chemists, leading to the discovery of distorted amides that exhibit a substantially reactive nature. Recent focus in this field is on the catalytic transformation of designed amides with moderate distortion or reduced resonance stabilization. This digest reviews the brief history of the quest for highly distorted amides and introduces a collection of recent studies on catalytic transformations of designed amides.     

Catalytic Cleavage of Amide C−N Bond: Scandium,Manganese, and Zinc Catalysts for Esterification of Amides

Amide C?N bonds are thermodynamically stable and their fission, such as by hydrolysis and alcoholysis, is considered a long‐challenging organic reaction. In general, stoichiometric chemical transformations of amides into the corresponding esters and acids require harsh conditions, such as strong acids/bases at a high reaction temperature. Accordingly, the development of catalytic reactions that cleave not only primary and secondary amides, but also tertiary amides in mild conditions, is in high demand. Herein, we surveyed typical stoichiometric transformations of amides, and highlight our recent achievements in the catalytic esterification of amides using scandium, manganese, and zinc catalysts, together with some recent catalyst systems using late‐transition metal reported by other groups.     

Thermodynamic investigation of the adsorption of amides on graphite from their liquids and binary mixtures

We report a thermodynamic investigation of the adsorption of saturated and unsaturated (cis- and trans-) alkyl amides onto the surface of graphite from their pure liquids and from binary mixtures. We identify the formation of solid monolayers of the amides at temperatures when the bulk materials are liquid. The extent of this presolidification is much more extensive than other related materials, indicating that these amide layers are significantly more stable. The monolayer stability is found to be greatest for saturated amides. In addition, the stability of unsaturated amides is extremely sensitive to the location of the double bonds in the alkyl chain of the molecules, and trans isomers are found to be more stable than cis. We also address the preferential adsorption and mixing behavior of amide mixtures and amides mixed with other species coadsorbed onto graphite from binary solution. The results indicate that the amide molecules appear to be adsorbed with their principal axis parallel to the graphite surface and that amides are found to be strongly preferentially adsorbed with respect to alkanes. Interestingly the amides appear to mix rather better than might have been expected. There is also evidence of a number of other transitions in the adsorbates.     

Electrochemical studies of copper fatty amides complex in organic medium

The electrochemical behavior of complexes of fatty amides, synthesized from vegetable oil, with Cu(II) has been investigated. In this study, a platinum electrode was used in presence of DMSO as a medium. Reduction of Cu(II)/fatty amides complex was found with quasi-reversible reaction. The peak potential of voltammetric behavior of fatty amides is about ?0.77 V at a scan rate v = 0.1 V s^?1 versus Ag|Ag⁺ electrode. This study shows that Cu(II)-fatty amides complex is poorly adsorbed on the electrode surface. Additionally, the copper complex form of fatty amides has a more stable structure than pure fatty amides to form the electrochemical reduction of the complex.     

Nucleophilic Arylation of N,O‐Ketene Acetals with Triaryl Aluminum Reagents: Access to α‐Aryl Amides through an Umpolung Process

A novel approach for the umpolung α‐arylation of amides is presented. By the nucleophilic phenylation of O‐silyl N,O‐ketene acetals, generated in situ from N‐alkoxy amides, a phenyl group can be introduced onto the α‐carbon atom of amides through N−O bond cleavage in a two‐step, one‐pot process. The asymmetric synthesis of α‐aryl amides through the diastereoselective arylation of a chiral N,O‐ketene acetal is also described.     

Cu-catalyzed arylation of phosphinic amide facilitated by (±)-trans-cyclohexane-1,2-diamine

Cu-catalyzed cross coupling between phosphinic amides and aryl halides was accomplished for the first time by using(±)-trans- cyclohexane-1,2-diamine as the ligand.This reaction provided a novel approach for synthesizing arylated phosphinic amides.Both kinetic measurement and theoretical calculation indicated that phosphinic amides were much less reactive than amides by about 10 times in Cu-catalyzed cross coupling.