Primary Amides Research Articles

NaHBEt3-catalyzed HBpin hydroboration and deoxygenation of primary, secondary, and tertiary amides

Herein, we used alkali metal to catalyze the hydroboration of amides, and hence provide a new route for the reduction of the amides. And we conducted a study of the mechanism of the reduction of primary amide by carrying out control experimental reactions.

Synthesis of quinazolinones via Cp*Co(III)-catalyzed C-H functionalization of primary amides with oxadiazolones.

Multi-heteroatom heterocycle synthesis through direct C-H bond activation is methodologically appealing but synthetically challenging. An efficient double C-N bond formation sequence to prepare quinazolinones utilizing primary amides and oxadiazolones in a catalytic redox-neutral [CoCp*(CO)I2]/AgSbF6 system, where oxadiazolone could function as an internal oxidant to maintain the catalytic cycle, is reported. Amide-directed C-H bond activation and oxadiazolone decarboxylation are key to the success of this traceless, atom- and step-economic, and cascade approach for the construction of the quinazolinone skeleton.

New boro amino amide organocatalysts for asymmetric cross aldol reaction of ketones with carbonyl compounds.

Distinct types of new boron fused primary amino amide organocatalysts were designed and synthesized from commercially available amino acids. Their catalytic activities were investigated in asymmetric crossed aldol reaction of ketones with aromatic aldehydes to afford the corresponding chiral anti-aldol adducts with good chemical yields, moderate diastereoselectivity and good to excellent enantioselectivities (up to 94% yields, up to 90 : 10 dr, up to 94% ee).

Novel Cholinesterase Inhibitors: Synthesis, in silico and in vitro Studies

The synthesis of new functionalized linear diaza and triaza phenothiazine and phenoxazines and their in silico and in vitro anti-Alzheimer activity is reported. Fifteen new amide derivatives (8-11 & 13-24) were synthesized by the reactions of phenothiazines/phenoxazine (6 or 12) and various aliphatic and aromatic primary amides (7) in the presence of nickel catalyst and anhydrous potassium carbonate under nitrogen atmosphere. The FTIR, 1H NMR, 13C NMR and HR-MS spectra of the synthesized compounds were in agreement with the assigned structures. All the 15 new derivatives were screened for their in silico and in vitro anti-Alzheimer’s activity using the inhibition of acetylcholinesterase and butyrylcholinesterase. The results of the in silico experiment showed that most of the synthesized derivatives had good binding energies, binding interaction and bond distances. The most active derivatives in the in silico studies was compounds 18 (-12.5 and -11.5 kcal/mol) against acetylcholinesterase and butyrylcholinesterase, respectively. In addition, compound 18 had the best in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase (99.37% and 82.35%). The results of in silico experiment were greatly in agreement with the results of in vitro studies. The structure-activity relationship studies revealed that the phenothiazine derivatives had better in silico and in vitro activities. Furthermore, 2-substitutted phenothiazines had better activity than the unsubstituted phenothiazines. The synthesized compounds showed promising in silico and in vitro activities against acetylcholinesterase and butyrylcholinesterase and as such could be further developed for the treatment of Alzheimer’s disease.

Potential precursors for terminal ytterbium(II) imide complexes bearing the hydrotris(3-tert-butyl-5-methylpyrazolyl)borato ligand.

Monomeric, divalent ytterbium primary amides TptBu,MeYb(NHR)(thf)x (R = C6H3iPr2-2,6 = AriPr = Dipp, C6H3(CF3)2-3,5 = ArCF3, SiPh3) supported by the bulky hydrotris(3-tBu-5-Me-pyrazolyl)borato scorpionate ligand are synthesized acccording to salt metathesis and protonolysis protocols, respectively. Yb(II) precursors comprise YbI2(thf)2, Yb[N(SiMe3)2]2(thf)2 and TptBu,MeYb[N(SiMe3)2]. Complexes TptBu,MeYb(NHR)(thf)x readily engage in donor (thf) exchange with nitrogen donors like DMAP (4-dimethylaminopyridine) and pyridine. Treatment of TptBu,MeYb(NHArCF3)(thf)2 with the Lewis acids AlMe3 and GaMe3 results in the heterobimetallic complexes TptBu,MeYb(NHArCF3)(MMe3) (M = Al, Ga). Reactions of TptBu,MeYb(NHR)(thf)x (R = AriPr, ArCF3) with the halogenating agents C2Cl6 and TeBr4 give access to trivalent complexes [TptBu,MeYb(NHR)(X)] (X = Cl, Br). The ytterbium(II) complexes under study display 171Yb NMR chemical shifts in the range 582 ppm for TptBu,MeYb(NHArCF3)(GaMe3) to 954 ppm for TptBu,MeYb(NHSiPh3)(dmap). The salt-metathesis route is also applicable for the synthesis of complexes TptBu,MeLn(NHAriPr)(thf) (Ln = Sm, Eu) and TptBu,MeYb(NHArMe) (ArMe = C6H3Me2-2,6).

Solvent-controlled amidation of acid chlorides at room temperature: new route to access aromatic primary amides and imides amenable for late-stage functionalization.

Herein, we report a solvent-controlled highly selective amidation and imidation of aroyl chlorides using an alkali-metal silyl-amide reagent (LiHMDS), which serves as a nitrogen source at room temperature. A unique feature of this method lies in the sequential silyl amidation of aryol chlorides and nitrogen-silicon bond cleavage of the corresponding N,N-bis(trimethylsilyl)benzamide in a one-pot method in a very short reaction time. This effective strategy was extended to late-stage functionalization.

Structures of nickel chloride and thiolate complexes supported by PCN and POCOP pincer ligands and catalytic reactivity of the chloride complexes.

Nickel chloride and thiolate complexes supported by benzene-pyridine-based nonsymmetrical PCN pincer ligands, [2-(tBu2PO)-6-(2-pyrindinyl-4-R)-C6H3]NiX (R = H, CH3, CF3; X = Cl, SH, SPh), were synthesized and fully characterized. The structures of these complexes and the catalytic reactivity of the chloride complexes were investigated along with the related POCOP counterparts [2,6-(tBu2PO)2C6H3]NiX (X = Cl, SH). It was found that the composition and substitution of the pincer backbone evidently influence the structures and catalytic reactivity. The Ni-P and Ni-Cipso bond lengths in the PCN complexes are significantly shorter than those in the POCOP complex. The Ni-Cl and Ni-S bond lengths in the PCN complexes are longer than those in the POCOP complexes. An electron rich pyrindinyl ring in the PCN complexes makes the Ni-Cl bond longer. The Ni-N bond length is more sensitive to the auxiliary ligand compared with the Ni-P bond length in the PCN complexes. The PCN chloride complexes were found to be active catalysts for selective hydration of nitriles to primary amides in the presence of NaOH at 80 °C and the catalytic activity increases with the increase of electron richness of the pyridinyl ring. However, the corresponding POCOP counterpart is inactive under the same conditions.

The copper-catalyzed oxidative radical process of site selective C–N bond cleavage in twisted amides: batch and continuous-flow chemistry

Copper-superoxo radical activation in twisted amides which mediates the aerobic oxidative process to produce primary amides by selective C–N bond cleavage in batch and continuous-flow method.

An electrochemical Hofmann rearrangement on acrylamide copolymers

Constant current electrolysis of acrylamide copolymers promotes a mild and efficient electrochemical Hofmann rearrangement transforming the primary amide side-chains into O-methyl carbamate side-chains in methanol.

Catalytic fate of structurally characterized manganese(iii)–salen complexes towards efficient transformation of primary amides to amines or nitriles using hydrosilane

Simple salen-based manganese(iii) complexes show excellent catalytic activity towards the hydrosilylative transformation of primary amides to their corresponding primary amines under mild reaction conditions.

Catalytic dehydrative amide bond formation using aqueous ammonia: synthesis of primary amides utilizing diboronic acid anhydride catalysis.

Although aqueous ammonia is an inexpensive and readily available safe source of ammonia, there have been no successful studies on direct catalytic dehydrative amidations of carboxylic acids with aqueous ammonia. In this study, we report a catalytic methodology for the synthesis of primary amides through diboronic acid anhydride (DBAA)-catalyzed dehydrative condensation of carboxylic acids with aqueous ammonia as the amine substrate.

Bicyclic (alkyl)(amino)carbene (BICAAC) in a dual role: activation of primary amides and CO2 towards catalytic N-methylation.

Herein, we report the first catalytic methylation of primary amides using CO2 as a C1 source. A bicyclic (alkyl)(amino)carbene (BICAAC) exhibits dual role by activating both primary amide and CO2 to carry out this catalytic transformation which enables the formation of a new C-N bond in the presence of pinacolborane. This protocol was applicable to a wide range of substrate scopes, including aromatic, heteroaromatic, and aliphatic amides. We successfully used this procedure in the diversification of drug and bioactive molecules. Moreover, this method was explored for isotope labelling using 13CO2 for a few biologically important molecules. A detailed study of the mechanism was carried out with the help of spectroscopic studies and DFT calculations.

Synthesis and catalytic performance of nickel phosphinite pincer complexes in deoxygenative hydroboration of amides.

A series of imino-POCNR, amino-POCNR2, and bis(phosphinite) POCOP pincer complexes of Ni(II) were prepared and tested in catalytic deoxygenative hydroboration of amides with HBPin to the corresponding amines. In contrast to the deoxygenative hydrosilylation approach, primarily developed for tertiary amides, superior reactivity in Ni-catalyzed deoxygenative hydroboration was demonstrated for secondary carboxamides. The bis(phosphinite) hydride complex (POCOP)NiH proved the most active in these reactions, tolerating potentially reducible functionalities such as internal alkenes, esters, nitriles, heteroaromatic compounds, and tertiary amides. Preferable hydroboration of secondary amides was also demonstrated in the presence of primary amide functionalities. The reactions were conducted at 60-80 °C, representing a rare example of a base-metal catalytic system for selective deoxygenation of secondary amides to the corresponding amines under mild conditions. In contrast to secondary amides, deoxygenative hydroboration of primary amides was demonstrated using an iminophosphinite pre-catalyst (POCNDmp)Ni(CH2TMS) (Dmp = 2,6-Me2C6H3). Deoxygenation reactions were suggested to proceed via a direct C-O bond cleavage mechanism, which is triggered by dehydrogenative N-borylation to access more electrophilic N-borylamides amenable to the addition of HBPin to the carbonyl group.

N,N'-(2-aryl-2-oxoethane-1,1-diyl)diamides as convenient synthons for the preparation of 3-amido-2-arylbenzofurans

The general method for the synthesis of 2-arylbenzofuran containing amides was elaborated. The considered approach is based on interaction of various phenols with N,N'-(2-aryl-2-oxoethane-1,1-diyl)diamides, which can be obtained from arylglyoxals and primary amides. The employment of formic acid as a solvent is necessary condition for the presented protocol. The undoubted advantage of the developed method is the possibility of using a wide range of aromatic hydroxyl derivatives. The dignity of this synthesis is readily accessible starting materials, mild reaction conditions, atom economy and easy workup procedure, which can avoid chromatographic purification. The structure of one of the target benzofurans was established by X-ray diffraction.

Stereoselective Synthesis of Enamides through Palladium‐Catalyzed Oxidative Amidation of Conjugated Olefins with 2‐Pyridones

AbstractA palladium‐catalyzed oxidative amidation of conjugated olefin with 2‐pyridone is described. A series of E‐Enamides were synthesized in a highly stereocontrolled manner. The reaction also accommodates other cyclic and acyclic amides. Z‐Enamides were predominantly prepared for primary amides probably due to the presence of an intramolecular hydrogen bond. Gram‐scale synthesis of enamide and the following oxidative annulation with diphenylacetylene demonstrates the synthetic utility of this reaction.

Synthesis of N-Acylsulfenamides from Amides and N-Thiosuccinimides.

Herein is reported a robust and general method for the preparation of N-acylsulfenamides, important functionalities that have recently been utilized as central inputs for the asymmetric synthesis of high oxidation state sulfur compounds. This straightforward transformation proceeds by reaction of primary amides, carbamates, sulfonamides, sulfinamides, and ureas with stable N-thiosuccinimides or N-thiophthalimides, which in turn are prepared in a single step from commercial thiols. The use of stable N-thiosuccinimide and N-thiophthalimide reactants is desirable because it obviates the use of highly reactive sulfenyl chlorides.

Catalytic Efficiency of Primary α-Amino Amides as Multifunctional Organocatalysts in Recent Asymmetric Organic Transformations

Chiral primary α-amino amides, consisting of an adjacent enamine bonding site (Bronsted base site), a hydrogen bonding site (Bronsted acid site), and flexible bulky substituent groups to modify the steric factor, are proving to be extremely valuable bifunctional organocatalysts for a wide range of asymmetric organic transformations. Primary α-amino amides are less expensive alternatives to other primary amino organocatalysts, such as chiral diamines and cinchona-alkaloid-derived primary amines, as they are easy to synthesize, air-stable, and allow for the incorporation of a variety of functional groups. In recent years, we have demonstrated the catalytic use of simple primary α-amino amides and their derivatives as organocatalysts for the aldol reaction, Strecker reaction, Michael tandem reaction, allylation of aldehydes, reduction of N-Aryl mines, opening of epoxides, hydrosilylation, asymmetric hydrogen transfer, and N-specific nitrosobenzene reaction with aldehydes.

Practical povidone iodine catalyzed transamidation from primary amides and amines

Non-harmful Povidone iodine (PVP-I) was applied in the transamidation to gain N-substituted amides from various primary amides and amines. Diverse aromatic, heterocyclic and aliphatic primary amides/amines were applied in our developed method and more than 45 N-substituted amides were obtained with excellent yields in most cases. Several drugs such as Melatonin and Efaproxiral were successfully acquired with a better performance than those previous reported results.

Kinetic Analysis of Consecutive/Parallel Transformation of Furfural to Biomass-Based Primary Amide by Using a “Concentration–Time” Integral

Kinetic Analysis of Consecutive/Parallel Transformation of Furfural to Biomass-Based Primary Amide by Using a “Concentration–Time” Integral

Synthesis of Novel Cavitand Host Molecules via Palladium-Catalyzed Aryloxy- and Azidocarbonylation

Novel, elongated, resorcine[4]arene-based cavitands were synthesized via various consecutive reaction steps, including homogeneous catalytic aryloxy- and azidocarbonylation processes. The effects of carbon monoxide pressure and temperature on the conversion were examined in aryloxycarbonylation. It was revealed that a reaction temperature of 100 °C is required to achieve complete conversion both with monodentate (PPh3) and bidentate (Xantphos) phosphines at different carbon monoxide pressures (1-40 bar). Using ten different phenols as O-nucleophiles, partial hydrolysis of the esters to the corresponding carboxylic acids took place-i.e., 58-90% chemoselectivities toward esters were obtained. Moreover, the influences of temperature, reaction time and the catalyst ratio on the selectivity and conversion were described in the case of azidocarbonylation reaction. The formation of the acyl azide with high chemoselevtivity can be achieved at room temperature only. The higher reaction temperatures (50 °C) and higher catalyst loadings favor the formation of the primary amide. The characterization of the target compounds (esters and acyl azides) was carried out by IR and 1H and 13C NMR. The discussion of the influences of various parameters is based on in situ NMR investigations.