Saturated Amides Research Articles

Nickel Boride as Hydride Source in Nickel Catalyzed Chemoselective Reduction of α,β‐Unsaturated Amides

AbstractA facile and highly efficient chemoselective reduction of α,β‐unsaturated amides leading to saturated amide has been described. In situ generated nickel boride was found to act as an efficient reagent for the conjugate reduction. The reaction proceeds smoothly under an inert atmosphere at ambient temperature with a moderate to good yield. Both aliphatic and aromatic α,β‐unsaturated amides were found to be compatible with the reaction protocol.

Cobalt-Catalyzed Enantioselective Hydrogenation of Trisubstituted Carbocyclic Olefins: An Access to Chiral Cyclic Amides.

The enantioselective hydrogenation of cyclic enamides has been achieved using an earth-abundant cobalt-bisphosphine catalyst. Using CoCl2 /(S,S)-Ph-BPE, several trisubstituted carbocyclic enamides were reduced with high activity and excellent enantioselectivity (up to 99 %) to the corresponding saturated amides. The methodology can be extended to the synthesis of chiral amines by base hydrolysis of the hydrogenation products. Preliminary mechanistic investigations reveal the presence of a high spin cobalt (II) species in the catalytic cycle. We propose that the hydrogenation of the carbon-carbon double bond proceeds via a sigma-bond-metathesis pathway.

Migrative Carbofluorination of Saturated Amides Enabled by Pd-Based Dyotropic Rearrangement

Directly editing an all-carbon quaternary carbon itself of nonstrained acyclic molecules remains underexploited despite the recent advances in the fields of both C-H and C-C bond activation. Herein, we report a palladium-catalyzed migrative carbofluorination of saturated amides enabled by the activation of both the C(sp3)-H and the Cquaternary-Cσ bonds. In this transformation, the α-quaternary carbon of Weinreb amides is converted to α-tertiary fluoride with concurrent migration of an aryl or an amido group from the α- to β-carbon. DFT calculations indicate that the dyotropic rearrangement proceeds through an unusual anti-selective [2.1.0] bicyclic transition state. The reaction, compatible with a broad range of functional groups, is stereospecific and is applicable to the synthesis of enantioenriched products.

Synthesis and antitumor activity of novel gibberellin derivatives with tetracyclic diterpenoid skeletons

Gibberellic acid (GA3) is a tetracyclic diterpene compound which displays interesting bioactivities. Recently, its potential use for preparing antitumor drug leads has been highlighted, and various modification methods of GA3 have been reported. Aiming at investigating GA3 derivatives with potential antitumor activities, ring distortion of GA3 under different conditions was carried out, and this was followed with amidation or substitution, yielding four series of derivatives. The chemical structure of these compounds were analyzed by 1H-NMR, 13C-NMR, HRMS, FTIR and polarimetry, and SXRD was employed to further confirm the spatial configurations of derivatives 3c and 7d. The antitumor activities of three series of derivatives were evaluated by using MTT assay and ELISA. Results shows that, among amide derivatives, compounds with a saturated linear amide showed better activity than those with an aromatic amide. Among ester derivatives, compounds with a meta-substituted benzyl group showed better activities than those with a para-substituted benzyl group. The antitumor activity of ester derivatives might possibly be linked with the inhibition of FGFR1 activation and KDR activation. Overall, this study discussed how the antitumor activity of GA3 was formed, thereby assisting the future design of more effective active GA3 derivatives.

Radical α,β-Dehydrogenation of Saturated Amides via α-Oxidation with TEMPO under Transition Metal-Free Conditions.

A transition metal-free radical process for the selective α,β-dehydrogenation of saturated amides under mild conditions is developed. Utilizing radical activation strategy, the challenging issue associated with the low α-acidity of amides is resolved. For the first time, α,β-unsaturated Weinreb amides and acrylamides could be efficiently prepared directly from corresponding saturated amides. Mechanistic studies confirm the radical nature of this transformation. Two gram scale α,β-dehydrogenation have also been performed to demonstrate the utility of this method.

Influences of ammonium and phosphate stimulation on metalworking fluid biofilm reactor development and performance

In this study, the effects of common wastewater stimulants, namely NH4Cl and KH2PO4, on the development and performance of metalworking fluid biofilm bioreactors are presented. It is shown that biofilms flourished only when one of these components was present in limiting quantities. Biofilm yields significantly declined when both of the components were withheld from the bioreactors or when both components were provided in excess. Stimulations to the reactors using NH4Cl significantly reduced the total carbon removal performance, while stimulations using KH2PO4 resulted in significant increases in performance. Chromatographic analyses showed that the NH4Cl stimulation enhanced the removal of saturated fatty amides and diethylene glycol butyl ether from the metalworking fluid, but inhibited the removal of diisoproponolamine. Furthermore, NH4Cl additions inhibited the oil/water separation carbon removal mechanism and resulted in the re-dispersion of recalcitrant organic material. The results from this study show that metalworking fluid practitioners should take care in choosing the nutrients used for stimulating bioreactor performance and microbe development. Incorrect stimulations with NH4Cl may result in negative treatment performances due to the inhibition of amine utilisation and enhancing emulsion stability.

NMR solution structure study of one saturated sulphur-containing amides from Glycosmis lucida

One sulphur-containing amide (N-[2-(4-Hydroxyphenyl)-ethyl]-3-methanesulfonyl-N-methyl-propionamide) which was isolated from Glycosmis lucida Wall ex Huang had a different NMR profile with this kind of compounds’ normal case. Based on the information obtained by nuclear magnetic resonance pectroscopy (NMR) and mass spectrometry (MS), its configurations in solution were investigated. The results indicated that the compound would have two stable configurations in solution as the double bond switched between C–N and C–O in an appropriate rate. This phenomenon was clearly exposed by the one dimension selective NOE (1D-NOE) experiments. This conclusion would play an active role in the structure analysis work of this kind of compounds.

Antileishmanial activity of amides from Piper amalago and synthetic analogs

Two natural amides isolated from the chloroform extract of Piper amalago L., Piperaceae, leaves, a hydrogenated derivative and seven synthetic analogs were tested against the promastigote and intracellular amastigote forms of Leishmania amazonensis. The antileishmanial activity was evaluated in terms of growth inhibitory concentration for 50% of protozoa (IC50). The cytotoxicity toward the J774A1 macrophages was evaluated in terms of the cytotoxic concentrations for 50% of macrophages (CC50). The ability to induce nitric oxide production was also investigated for all compounds. The saturated amide 7-(1,3-benzodioxol-5-yl)-1-(1-pyrrolidinyl)- 1-heptanone was obtained by hydrogenation of the natural compound N-[7-(3’,4’- methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl]pyrrolidine. Synthetic amides were prepared by addition of the appropriate amine to the corresponding acyl chloride. The natural compound, N-[7-(3’,4’-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine, was the most active of all tested compounds against the promastigote and intracellular amastigote forms with IC50 values of 15μM and 14.5μM, respectively. None of the compounds modulated the production of nitric oxide.

Amide proton transfer imaging of 9L gliosarcoma and human glioblastoma xenografts

Amide proton transfer (APT) imaging is a variant of magnetization transfer (MT) imaging, in which the contrast is determined by a change in water intensity due to chemical exchange with saturated amide protons of endogenous mobile proteins and peptides. In this study, eight Fisher 344 rats implanted with 9L gliosarcoma cells and six nude rats implanted with human glioblastoma cells were imaged at 4.7 T. There were increased signal intensities in tumors in the APT-weighted images. The contrast of APT imaging between the tumor and contralateral brain tissue was about 3.9% in water intensity (1.49 +/- 0.66% vs -2.36 +/- 0.19%) for the more uniformly hypercellular 9L brain tumors, and it was reduced to 1.6% (-1.18 +/- 0.60% vs -2.77 +/- 0.42%) for the human glioblastoma xenografts that contained hypocellular zones of necrosis. The preliminary results show that the APT technique at the protein level may provide a unique MRI contrast for the characterization of brain tumors.

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.

C4-Substituted Isoquinolines: Synthesis and Cytotoxic Action

A facile synthesis of the C4-substituted isoquinolines 5a-c and 6a-c is described. Commercially available 4-bromoisoquinoline is converted to the α,β-unsaturated esters 8 and 10 on treatment with the appropriate acrylate ester under Heck reaction conditions. The saturated amides 5a-c were obtained from the reaction of ester 9 with the requisite primary amine. Similarly the unsaturated analogues 6a-c were prepared by reacting ester 10 with the appropriate amine. The cytotoxicity of the target molecules was evaluated in two tumour cell lines in vitro. Two compounds, 6b and 6c, showed sufficient activity in the human non-small cell lung cancer line NSCLC-N16-L16 to be worthy of further study.

Tris(2,4,6-Trimethoxyphenyl)phosphine: Base Catalyst in the Transformation of α,β-Unsaturated Aldehydes to Saturated Carboxylic-Acid Derivatives

We have focused on the basicity of Tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP) in organic synthesis. To extend the utility of TTMPP, we examined the reaction of α,β-unsaturated aldehydes with trimethylsilyl cyanide in the presence of TTMPP. Furthermore, to clarify the basic character of TTMPP, we measured 31P NMR of TTMPP and related compounds. First, the reaction of cinnamaldehydes with trimethylsilyl cyanide in the presence of a catalytic amount of TTMPP afforded the corresponding saturated carboxylic acids after hydrolysis with 1M HCl. Treatment of the reaction mixture with alcohols or amines instead of 1M HCl gave the corresponding saturated esters and amides, respectively. As a result of studies of the reaction mechanism, it was revealed that the reaction proceeded via silylcyanation of α,β-unsaturated aldehydes with trimethylsilyl cyanide to produce trimethylsilyl ethers of cyanohydrin and subsequent isomerization that formed α-trimethylsiloxy vinyl cyanides, which were hydrolyzed to give saturated carboxylic acids.

Superacidic Activation of α,β‐Unsaturated Amides and Their Electrophilic Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Superacidic Activation of α,β‐Unsaturated Amides and Their Electrophilic Reactions

AbstractThe electrophilic reactivity of α,β‐unsaturated amides towards weak nucleophiles such as arenes and cyclohexane, initiated either with triflic acid (CF3SO3H) or with excess AlCl3, has been studied. The amides generally condense readily with aromatics in the presence of AlCl3 to give 3‐arylpropionamides and related compounds in excellent yields, while some amides also undergo selective ionic hydrogenation with cyclohexane to give saturated amides. The proposed mechanism of these reactions involves dicationic intermediates (superelectrophiles). The direct observation of a dicationic species (by low‐temperature NMR) is reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Zur Synthese von (Z)‐ und (E)‐3‐(1H‐Imidazol‐4‐yl)‐2‐propenamin und einigen 3‐(1H‐Imidazol‐4‐yl)propanaminen

Synthesis of (Z)‐ and (E)‐3‐(1H‐imidazol‐4‐yl)‐2‐propenamine and Some 3‐(1H‐imidazol‐4‐yl)propanamines3‐(1H‐Imidazol‐4‐yl)propanamine (6, homohistamine), an essential intermediate for the synthesis of potent impromidine‐type histamine H2 receptor agonists, is efficiently prepared from trans‐urocanic acid (1) by reduction of the methyl ester 2 and conversion to the saturated amide 4. Dehydration with thionyl chloride yields the nitrile 5 which is subsequently reduced to 6. Side‐chain methylated 3‐(1H‐imidazol‐4‐yl)propanamines 12 are available from 1H‐imidazole‐4‐carbaldehyde (7) and 1‐(1H‐imidazol‐4‐yl)ethanone (8), respectively, via unsaturated nitriles 10 and stepwise reduction. Cyclization of the appropriate 4‐bromo‐5‐oxohexanenitriles 14α with formamidine in liquid ammonia and reduction of the obtained nitriles 15 furnishes ring‐methylated amines 16. (E)‐3‐(1H‐Imidazol‐4‐yl)‐2‐propenamine [(E)‐23] is obtained in six steps from the trans‐ester 2 while (Z)‐23 is accessible by treating 7 with triphenyl(2‐phthalimidoethyl)phosphonium bromide (17) and final deprotection. These primary amines are valuable intermediates for the synthesis of impromidine analogues.

Amidoselenation of Olefins Using p-Toluenesulfonamide as a Nitrogen Nucleophile

Abstract The reaction of olefins, benzeneselenenyl chloride, and p-toluenesulfonamide in the presence of zinc(II) chloride affords N-[2-(phenylseleno)alkyl]-p-toluenesulfonamides in good to excellent yields. When combined with alkylation on the carbon atom bearing the phenylseleno group thus introduced and subsequent oxidative or reductive removal of the selenium moiety, this reaction can be utilized in the preparation of a wide range of allylic or saturated amides.

ChemInform Abstract: Studies on the Synthesis of Antiulcer Agents. Part 5. Synthesis and Antiulcer Activity of Dihydrobenzofuranone Derivatives.

AbstractThe cinnamate (I) is hydrogenated, then hydrolyzed, and subsequently aminated to produce the saturated amides (IV).

Monometallic, homo- and hetero-bimetallic complexes based on redox active tris(3,5-dimethylpyrazolyl)borato molybdenum and tungsten nitrosyls. Part 6. Synthesis and electrochemistry of complexes containing saturated heterocyclic amide ligands. X-Ray crystal and molecular structure of [{Mo(NO)[HB(Me2pz)3]Cl}2(NC4H8N)

The co-ordinatively unsaturated complexes [M(NO){HB(Me2pz)3}Cl(Y)][M = Mo or W; Y = NC3H6–, NC4H8–, or NC5H10–; HB(Me2pz)3= hydrotris(3,5-dimethylpyrazolyl)borate] have been prepared and characterised. All exhibit reversible one-electron reduction processes in their cyclic voltammograms. The bimetallic species [{M(NO)[HB(Me2pz)3]Cl}2(NC4H8N)](M = Mo or W) were also prepared, and the molybdenum complex structurally characterised by an X-ray diffraction study which revealed a chair conformation for the bridging piperazine-1,4-diyl ligand (NC4H8N). The molybdenum atoms are oriented essentially equatorially with Mo ⋯ Mo separation 6.773(2)A. These bimetallic species appear to behave as ‘strongly interacting’ redox systems. In the case of M = Mo two one-electron reduction processes, separated by 560 mV, were observed by cyclic voltammetry.

Synthesis of new α-chloroacryl-amides, thioamides and amidines from saturated amides

Chorination of saturated amide-chlorides followed by hydrolysis, thiolysis, aminolysis and catalysed dehydrochlorination leads to α-chloro acrylamide derivatives in high yield. The reaction sequence is applied to lactames and can also be extended to the synthesis of α-chloro acrylthioamide and amidine.

Dehydro-enkephalins. IV. Discriminative recognition of delta and mu opiate receptors by enkephalin analogs

We have studied the receptor binding activities of C -terminal free and amidated enkephalins with and without the dehydrophenylalanine 4 residue. For the selective labeling of so-called δ and μ opiate receptors, specific tracers were used at low concentrations in rat brain membranes and neuroblastoma cells containing pure δ receptors. C -Terminal free enkephalins are five to eight times more potent in the assay for δ receptors than in μ assay, while the amides are almost equipotent in both assays. The presence of a C-terminal carboxyl group is a determining factor for selective activity. [D-Ala 2, ΔPhe 4, Met 5]-enkephalin amide is very potent in all of the binding assays examined, and, in particular, twice as active as the saturated amide and the C -terminal free enkephalin in the δ assay. We suggest that the steric arrangement of the dehydrophenylalanine residue in position 4 is very important to the enhanced interaction with the δ receptors.