Showing papers on "Piperidine published in 2011"

Cerium Ammonium Nitrate-Catalyzed Multicomponent Reaction for Efficient Synthesis of Functionalized Tetrahydropyridines

Abstract: A highly atom-economic one-pot synthesis of functionalized tetrahydropyridines by a multicomponent condensation reaction of β-keto ester, two equivalents of aromatic aldehyde, and two equivalents of amine in the presence of a catalytic amount of cerium ammonium nitrate (CAN) is reported. In this way, a series of pharmacologically interesting substituted piperidine derivatives were obtained in moderate to good yields at room temperature.

Piperidine derivatives and compositions for the inhibition of nicotinamide phosphoribosyltransferase (nampt)

Abstract: The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below: Formula (I)

Mannich–Michael versus formal aza-Diels–Alder approaches to piperidine derivatives

Abstract: A review into the aza-Diels–Alder reaction, mainly concentrating on literature examples that form piperidin-4-ones from the reaction of imines and electron rich dienes or enones, either through a Lewis acidic/Bronsted acid approach or through the use of an organocatalyst This review questions whether the mechanism of the aza-Diels–Alder reaction is step wise as opposed to concerted when using oxygenated dienes

Well-defined N-heterocyclic carbene silver halides of 1-cyclohexyl-3-arylmethylimidazolylidenes: synthesis, structure and catalysis in A3-reaction of aldehydes, amines and alkynes

Abstract: Structurally well-defined N-heterocyclic carbene silver chlorides and bromides supported by 1-cyclohexyl-3-benzylimidazolylidene (CyBn-NHC) or 1-cyclohexyl-3-naphthalen-2-ylmethylimidazolylidene (CyNaph-NHC) were synthesized by reaction of the corresponding imidazolium halides with silver(I) oxide while cationic bis(CyBn-NHC) silver nitrate was isolated under similar conditions using imidazolium iodide in the presence of sodium nitrate. Single-crystal X-ray diffraction revealed a dimeric structure through a nonpolar weak-hydrogen-bond supported Ag–Ag bond for 1-cyclohexyl-3-benzylimidazolylidene silver halides [(CyBn-NHC)AgX]2 (X = Cl, 1; Br, 2) but a monomeric structure for N-heterocyclic carbene silver halides with the more sterically demanding 1-cyclohexyl-3-naphthalen-2-ylmethylimidazolylidene ligand (CyNaph-NHC)AgX (X = Cl, 4; Br, 5). Cationic biscarbene silver nitrate [(CyBn-NHC)2Ag]+NO3−3 assumed a cis orientation with respect to the two carbene ligands. The monomeric complexes (CyNaph-NHC)AgX 4 and 5 showed higher catalytic activity than the dimeric [(CyBn-NHC)AgX]21 and 2 as well as the cationic biscarbene silver nitrate 3 in the model three component reaction of 3-phenylpropionaldehyde, phenylacetylene and piperidine with chloride 4 performing best and giving product in almost quantitative yield within 2 h at 100 °C. An explanation for the structure–activity relationship in N-heterocyclic carbene silver halide catalyzed three component reaction is given based on a slightly modified mechanism from the one in literature.

An FTIR spectroscopic study on the effect of molecular structural variations on the CO2 absorption characteristics of heterocyclic amines.

Abstract: Herein, the reaction between CO(2) and piperidine, as well as commercially available functionalised piperidine derivatives, for example, those with methyl-, hydroxyl- and hydroxyalkyl substituents, has been investigated. The chemical reactions between CO(2) and the functionalised piperidines were followed in situ by using attenuated total reflectance (ATR) FTIR spectroscopy. The effect of structural variations on CO(2) absorption was assessed in relation to the ionic reaction products identifiable by IR spectroscopy, that is, carbamate versus bicarbonate absorbance, CO(2) absorption capacity and the mass-transfer coefficient at zero loading. On absorption of CO(2) , the formation of the carbamate derivatives of the 3- and 4-hydroxyl-, 3- and 4-hydroxymethyl-, and 4-hydroxyethyl-substituted piperidines were found to be kinetically less favourable than the carbamate derivatives of piperidine and the 3- and 4-methyl-substituted piperidines. As the CO(2) loading of piperidine and the 3- and 4-methyl- and hydroxyalkyl-substituted piperidines exceeded 0.5 moles of CO(2) per mole of amine, the hydrolysis of the carbamate derivative of these amines was observed in the IR spectra collected. From the subset of amines analysed, the 2-alkyl- and 2-hydroxyalkyl-substituted piperidines were found to favour bicarbonate formation in the reaction with CO(2) . Based on IR spectral data, the ability of these amines to form the carbamate derivatives was also established. Computational calculations at the B3LYP/6-31+G** and MP2/6-31+G** levels of theory were also performed to investigate the electronic/steric effects of the substituents on the reactivity (CO(2) capture performance) of different amines, as well as their carbamate structures. The theoretical results obtained for the 2-alkyl- and 2-hydroxyalkyl-substituted piperidines suggest that a combination of both the electronic effect exerted by the substituent and a reduction in the exposed area of the nitrogen atom play a role in destabilising the carbamate derivative and increasing its susceptibility to hydrolysis. A theoretical investigation into the structure of the carbamate derivatives of these amines revealed shorter NC bond lengths and a less-delocalised electron distribution in the carboxylate moiety.

Palladium-catalyzed ring-contraction and ring-expansion reactions of cyclic allyl amines.

Abstract: The ring-contraction of seven- and eight-membered allylic amines provides pyrrolidine and piperidine derivatives.

Metal complexes of Co, Ni and Cu with the pincer ligand HN(CH2CH2PiPr2)2: preparation, characterization and electrochemistry

Abstract: A series of Co, Ni and Cu complexes with the ligand HN(CH2CH2PiPr2)2 (HNP2) has been isolated and their electrochemical behaviour investigated by cyclic voltammetry. The nickel complexes [(HNP2)NiOTf]OTf and [(HNP2)NiNCCH3](BF4)2 display reversible reductions, as does the related amide derivative (NP2)NiBr. The related copper(I) and cobalt(II) derivatives were also isolated and characterized. The addition of piperidine to [(HNP2)NiNCCH3](BF4)2 led to the formation of the new species [(HNP2)Ni(N(H)C(CH3)NC5H10)](BF4)2. The nucleophilic addition of piperidine to acetonitrile to produce HNC(CH3)NC5H10 was found to be catalyzed by [(HNP2)NiNCCH3](BF4)2.

Organocatalytic Conjugate Addition of Malononitrile to Conformationally Restricted Dienones

Abstract: Organocatalytic conjugate addition of malononitrile to conformationally restricted dienones has been studied. A series of chiral primary and tertiary amine catalysts were screened. A piperidine-based thiourea-tertiary amine was found to be the efficient catalyst. Chiral pyran derivatives were obtained in excellent yields and enantioselectivities via a cascade conjugate addition-intramolecular cyclization pathway. The reaction is remarkably different for the corresponding reaction of conformationally flexible dienones.

Copper(I) thiocyanate-amine networks: synthesis, structure, and luminescence behavior.

Abstract: A series of metal–organic networks of CuSCN were prepared by direct reactions with substituted pyridine and aliphatic amine ligands, L. Thiocyanate bridging is seen in all but 1 of 11 new X-ray structures. Structures are reported for (CuSCN)L sheets (L = 3-chloro- and 3-bromopyridine, N-methylmorpholine), ladders (L = 2-ethylpyridine, N-methylpiperidine), and chains (L = 2,4,6-collidine). X-ray structures of (CuSCN)L2 are chains (L = 4-ethyl- and 4-t-butylpyridine, piperidine, and morpholine). A unique N-thiocyanato monomer structure, (CuSCN)(3-ethylpyridine)3, is also reported. In most cases, amine ligands are thermally released at temperatures <100 °C. Strong yellow-to-green luminescence at ambient temperature is observed for the substituted pyridine complexes. High solid state quantum efficiencies are seen for many of the CuSCN-L complexes. Microsecond phosphorescence lifetimes seen for CuSCN-L are in direct contrast to the nanosecond-lifetime emission of CuSCN. MLCT associated with pyridine π* orbital...

Role of Piperine As A Bioavailability Enhancer

Abstract: Piperine is an alkaloid responsible for the pungency of black pepper and long pepper, along with chavicine (an isomer of piperine). It has also been used in some forms of traditional medicine and as an insecticide. Long pepper (Piper longum) and Black pepper (Piper nigrum), the active compound in both Piper longum and Piper nigrum is piperine (1-piperoyl piperidine) which is responsible for bioenhancing effect. It is shown to possess bioavailability enhancing activity with various structurally and therapeutically diverse drugs. It has been found that piperine's bioavailability-enhancing property may be attributed to increased absorption, which may be due to alteration in membrane lipid dynamics and change in the conformation of enzymes in the intestine. Piperine has been demonstrated to increase the serum levels and lengthen the serum half lives of some nutritional substances, such as coenzyme Q10 and beta-carotene. The mechanism of this action is unknown. It is speculated that piperine may act as a so-called thermonutrient and increase the absorption of certain nutritional substances from the gastrointestinal tract by producing a local thermogenic action. The present review is an attempt to highlight the bioenhancing ability of piperine when it is given along with various drugs and nutrients.

SmI2-mediated radical cross-couplings of α-hydroxylated aza-hemiacetals and N,S-acetals with α,β-unsaturated compounds: asymmetric synthesis of (+)-hyacinthacine A2, (-)-uniflorine A, and (+)-7-epi-casuarine.

Abstract: The SmI2-mediated radical coupling reactions of β-hydroxylated pyrrolidine/piperidine aza-hemiacetals 8 and 9 and N,S-acetals 6 and 33 with α,β-unsaturated compounds are described. This method allows a rapid access to β-hydroxylated pyrrolidines, piperidines, pyrrolizidinones, and indolizidinones. Starting from N,S-acetal 33 and via a common intermediate 27, the alkaloids hyacinthacine A2 (2), uniflorine A (3, 6-epi-casuarine), and the unnatural epimer 7-epi-casuarine (37) have been synthesized in four and five steps with overall yields of 34%, 16%, and 13%, respectively. The radical mechanism of the coupling reactions has been confirmed by controlled experiments, which also allowed deducing the anionic mechanism in the coupling between N,S-acetal 6 and carbonyl compounds. This demonstrates that the mechanisms of these SmI2-mediated reactions are switchable from Barbier-type anionic to radical by cooperative action of BF3·OEt2 and t-BuOH.

One-pot Zn/CuI/TFA-catalyzed domino three-component-carbocyclization reaction involving biphenyl-2-carbaldehydes/alkynes/piperidine: allenes-mediated construction of phenanthrenes.

Abstract: A one-pot protocol involving Zn/CuI/TFA-catalyzed domino three-component and subsequent carbocyclization reactions is described. The reaction proceeds via formation of propargyl amines from biphenyl-2-carbaldehydes/terminal alkynes/piperidine followed by the elimination of piperidine and ring closure to furnish phenanthrene derivatives in good yields. The strategy involves C(sp)-H activation–CH functionalization with imine-alkyne activation–1,5 hydride shift−β-elimination of piperidine–allene formation–6π cycloaddition–isomerization domino sequence. Evidence for the involvement of allenes as an intermediate during carbocyclization is discussed.

Efficient total synthesis of (+)-dihydropinidine, (-)-epidihydropinidine, and (-)-pinidinone.

Abstract: The 2,6-disubstituted piperidine alkaloids (+)-dihydropinidine (1), (−)-epidihydropinidine (2) (as HCl salts), and (−)-pinidinone (3) were efficiently synthesized from (S)-epichlorohydrin (7) as common substrate using regioselective Wacker−Tsuji oxidation of alkenylazides 10 and 14 as well as a highly diastereoselective reduction of cyclic imine 11 as key steps. The protecting group free total syntheses represent the up to date shortest routes with highest overall yields for all three naturally occurring alkaloids (1−3). The first single-crystal X-ray analysis of (−)-epidihydropinidine hydrochloride (2·HCl) confirmed its proposed absolute configuration to be (2S,6S), corresponding to that of the isolated natural product.

Covalent inhibitors of fatty acid amide hydrolase: a rationale for the activity of piperidine and piperazine aryl ureas.

Abstract: Recently, covalent drugs have attracted great interest in the drug discovery community, with successful examples that have demonstrated their therapeutic effects. Here, we focus on the covalent inhibition of the fatty acid amide hydrolase (FAAH), which is a promising strategy in the treatment of pain and inflammation. Among the most recent and potent FAAH inhibitors (FAAHi), there are the cyclic piperidine and piperazine aryl ureas. FAAH hydrolyzes efficiently the amide bond of these compounds, forming a covalent enzyme–inhibitor adduct. To rationalize this experimental evidence, we performed an extensive computational analysis centered on piperidine-based PF750 (1) and piperazine-based JNJ1661010 (2), two potent lead compounds used to generate covalent inhibitors as clinical candidates. We found that FAAH induces a distortion of the amide bond of the piperidine and piperazine aryl ureas. Quantum mechanics/molecular mechanics ΔELUMO–HOMO energies indicate that the observed enzyme-induced distortion of the...

Synthesis of new substituted chromen[4,3-c]pyrazol-4-ones and their antioxidant activities.

Abstract: A series of new coumarin derivatives 4 containing a 4-arylbut-3-en-2-one moiety were synthesized by condensation of 3-acetylcoumarin 1 with aryl aldehydes 2 in chloroform in the presence of piperidine. The interactions of 3-formyl-4-chlorocoumarin (3) with nitrogen-containg nucleophiles leading to the corresponding substituted chromen-[4,3-c]pyrazol-4-ones 5 are described. The structures of the obtained compounds were established on the basis of 1D NMR, 2D NMR and IR and further the compounds were evaluated for possible antioxidant activities. The coumarinic chalcone 4a has been found to be the most active (IC50 = 2.07 μM) in this study.

Friedländer Annulation in the Synthesis of Azaheterocyclic Compounds

Abstract: Publisher Summary Since 1882, when Friedlander reported the synthesis of quinolines from the condensation of o-aminoaryl carbonyl compounds and enolizable methylene groups, this method has become more and more popular in azaheterocyclic synthesis. This versatile method is used for the preparation of a large number of nitrogen-containing heterocyclic compounds, such as quinoline derivatives, pyridines, camptothecins, acridines, tacrine analogs, phenanthrolines, naphthyridines, anthyridines, and anthrazoline derivatives. This chapter discusses the application of Friedlander type methods in all these broad ranges of heterocyclic syntheses, highlighting old and recent research that has been carried out in this field. The simplest azaheterocycles that can be synthesized via the Friedlander mechanism are the quinolines. Classical Friedlander reactions are generally carried out by refluxing either an aqueous or an alcoholic solution of reactants in the presence of a base. Alternatively, the reaction is performed by heating a mixture of the reactants at temperatures ranging from 150 to 220C in the absence of a catalyst. Typical catalysts for the Friedlander reaction include bases, such as piperidine, sodium ethoxide, sodium tert-butoxide, KOH, NaOH, and MeONa.

Asymmetric synthesis of 1-deoxyazasugars from chiral aziridines

Abstract: A general and facile synthesis of enantiopure 1-deoxyazasugars was achieved from stereoselective dihydroxylation of a common synthetic intermediate, piperidine ring fused oxazolidin-2-one, originating from a commercially available starting substrate, chiral aziridine-2-carboxylate, in high yields.

Gold(I) catalysts with bifunctional P, N ligands.

Abstract: A series of phosphanes with imidazolyl substituents were prepared as hemilabile PN ligands. The corresponding gold(I) complexes were tested as bifunctional catalysts in the Markovnikov hydration of 1-octyne, as well as in the synthesis of propargylamines by the three component coupling reaction of piperidine, benzaldehyde, and phenylacetylene. While the activity in the hydration of 1-octyne was low, the complexes are potent catalysts for the three component coupling reaction. In homogeneous solution the conversions to the respective propargylamine were considerably higher than under aqueous biphasic conditions. The connectivity of the imidazolyl substituents to the phosphorus atom, their substitution pattern, as well as the number of heteroaromatic substituents have pronounced effects on the catalytic activity of the corresponding gold(I) complexes. Furthermore, formation of polymetallic species with Au2, Au3, and Au4 units has been observed and the solid-state structures of the compounds [(5)2Au3Cl2]Cl a...