Showing papers on "Morpholine published in 2004"
TL;DR: A series of cationic ruthenium(VI) nitrido species containing the cyclohexyl-bridged salen ligand (L) and its derivatives, [RuVI(N)(L)]+, have been prepared by treatment of [NBun4][Ru VI(N)Cl4] with H2L in methanol.
Abstract: A series of cationic ruthenium(VI) nitrido species containing the cyclohexyl-bridged salen ligand (L) and its derivatives, [RuVI(N)(L)]+, have been prepared by treatment of [NBun4][RuVI(N)Cl4] with H2L in methanol. The structure of [RuVI(N)(L)](ClO4) (1a) has been determined by X-ray crystallography, d(Ru⋮N) = 1.592 A. In solvents such as DMF or DMSO, [RuVI(N)(L)]+ undergoes a facile N···N coupling reaction at room temperature to produce N2 and [RuIII(L)(S)2]+ (S = solvent). 1a reacts rapidly with secondary amines to produce diamagnetic RuIV−hydrazido(1−) species, [RuIV(N(H)NR2)(L)(HNR2)]+. The reaction with morpholine is first order in RuVI and second order in morpholine with k(CH3CN, 25 °C) = 2.08 × 106 M-2 s-1. This rate constant is over 4 orders of magnitude larger than that of the corresponding reaction of the electrophilic osmium nitride, trans-[OsVI(N)(tpy)(Cl)2]+, with morpholine. The structure of [Ru(NHNC4H8)(L)(NHC4H8)](PF6)2 has been determined by X-ray crystallography, the Ru−N(hydrazido) dist...
95 citations
TL;DR: Topological analyses show that the crystal structures of piperazine, piperidine and morpholine are closely related to that of cyclohexane-II, which can be described in terms of a pseudo-cubic close-packed array of molecules in a familiar ABC layered arrangement.
Abstract: The crystal structures of piperazine, piperidine and morpholine have been determined at 150 K. All three structures are characterized by the formation of NH⋯N hydrogen-bonded chains. In piperazine these are linked to form sheets, but the chains are shifted so that the molecules interleave. In morpholine there are in addition weak CH⋯O interactions. Topological analyses show that these three structures are closely related to that of cyclohexane-II, which can be described in terms of a pseudo-cubic close-packed array of molecules in a familiar ABC layered arrangement. While the positions of the molecules within each layer are similar, hydrogen bonding occurs between the ABC layers and in order to accommodate this the molecules are rotated relative to those in cyclohexane-II. Piperidine and morpholine also adopt layered structures, with hydrogen-bonding or CH⋯O interactions between the layers. In these cases, however, the layering more resembles a hexagonal close-packed arrangement.
89 citations
TL;DR: A 3D-QSAR analysis using the GRID/GOLPE methodology was performed to get a better understanding of the relationship between chemical structure and biological activity, and found that the size of the morpholine or 1,4-oxazepane ring seems to be important for affinity.
Abstract: Since the identification of the dopamine D4 receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D4 ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthesis of a new series of 2,4-disubstituted morpholines and 2,4-disubstituted 1,4-oxazepanes with selectivity for the dopamine D4 receptor. A 3D-QSAR analysis using the GRID/GOLPE methodology was performed with the purpose to get a better understanding of the relationship between chemical structure and biological activity. Inspection of the coefficient plots allowed us to identify that regions which are important for affinity are situated around the two benzene ring systems, a p-chlorobenzyl group, and the aliphatic amine belonging to the morpholine or 1,4-oxazepane system. In addition, the size of the morpholine or 1,4-oxazepane ring seems to be important for affinity.
79 citations
TL;DR: In this paper, the biological relevance of C-substituted morpholines, their synthesis and important applications in other syntheses are discussed, and a review of morpholine synthesis is presented.
Abstract: C-Functionalized morpholines are found in a variety of natural products and biologically active compounds, but have also for other reasons been applied in organic synthesis. This review deals with the biological relevance of C-substituted morpholines, their synthesis and important applications in other syntheses. 1 Introduction 2 Biological Relevance of Morpholines 2.1 Naturally Occurring Morpholines 2.2 Bioactive Morpholines 2.2.1 Antidepressants 2.2.2 Appetite Suppressants 2.2.3 Antitumor Activity 2.2.4 Antioxidants 2.2.5 Miscellaneous 3 Morpholine Synthesis 3.1 Synthesis from Amino Alcohols 3.2 Synthesis from Epoxides 3.3 Synthesis via Organometallic Reactions 3.4 Synthesis from Olefins 3.5 Synthesis from Carboxylic Acid Derivatives 3.6 Miscellaneous 4 Morpholines as Synthetic Tools 4.1 The Williams Chiral Auxiliary 4.2 Chiral Auxiliaries 5 Conclusions.
70 citations
TL;DR: Enantio- and diastereoselective syntheses of trans-2,5-disubstituted morpholine derivatives are described, addressing the problem of regioselectives hydroxyl activation-ring closure of the resulting amino diol adducts for (amino alcohol-derived) alkyl substituents of different steric demands.
64 citations
TL;DR: In this article, a new Mannich base, N-(1-morpholinobenzyl) semicarbazide (MBS), formed by the condensation of morpholine, semicarazide and benzaldehyde, and its Cu(II, Ni(II), Co(II) and Zn-II complexes have been synthesized.
Abstract: A new Mannich base, N-(1-morpholinobenzyl) semicarbazide (MBS), formed by the condensation of morpholine, semicarbazide and benzaldehyde, and its Cu(II), Ni(II), Co(II) and Zn(II) complexes have been synthesized. Their structures have been elucidated on the basis of analytical, magnetic, electrical conductivity and spectral study as well as elemental analyses. The complexes exhibit square-planar geometry. The monomeric and non-electrolytic nature of the complexes is evidenced by their magnetic susceptibility and low conductance data. The electrochemical property of the ligand and its complexes in acetonitrile solution was studied by cyclic voltammetry. The X-band ESR spectra of the Cu(II) complex in DMSO at 300 and 77 K were recorded and their salient features are reported
61 citations
TL;DR: The Schiff bases and their ruthenium(II) complexes have been tested in vitro to evaluate their activity against bacteria, viz., Staphylococcus aureus (209p) and E. coli (ESS 2231), which indicate that the Ru-N bonds present in the complexes containing heterocyclic nitrogen bases are stronger than theRu-P.
53 citations
TL;DR: In vitro antitumor activity has been screened towards human adenocarcinoma cell lines and showed significant inhibition even at very low concentration.
46 citations
TL;DR: N-Alkyl- and N-fluoroalkyl-substituted oxazolidinium- and morpholinium-based quaternary salts and ionic liquids have been synthesized and characterized and are thermally stable with long liquid ranges as determined by thermal gravimetric analyses.
Abstract: N-Alkyl- and N-fluoroalkyl-substituted oxazolidinium- and morpholinium-based quaternary salts and ionic liquids have been synthesized and characterized. Reactions of N-methyloxazolidine (1) or N-methylmorpholine (2) with 3-fluoropropyl bromide or iodopropane in THF at 25 °C gave the quaternary salts (3a,b, 4a,b). These salts were metathesized with various metal salts to yield the corresponding ionic liquids (5a−h, 6a−i). N-Alkoxyethyl- and N-(fluoroalkoxy)ethyl-substituted morpholines (8−11) were prepared and quaternized with methyl iodide (8a−11a). Their corresponding ionic liquids (12−18) were obtained by anion exchange and characterized. For both series of compounds, nitrate, hexafluorophosphate, perchlorate, triflate, and bis(trifluoromethanesulfonyl)amide were utilized. Most of the final products are liquids at 25 °C and are thermally stable with long liquid ranges as determined by thermal gravimetric analyses. For compounds 12, 16, and 18, thermal stabilities of ≥400 °C were observed. All the new co...
46 citations
TL;DR: Trans-3,5-Bis(benzyl/tert-butyldiphenylsilyloxymethyl)morpholines, promising candidates for the C(2)-symmetric class of chiral reagents, were prepared with excellent optical purity and extended to the synthesis of potentially useful chiral building block.
44 citations
TL;DR: The enaminones 1b,d,f react with 4-phenyl-3-methyl-5-pyrazoleamine 3a to yield the pyrazole derivatives 4a-c that cyclised readily on reflux in pyridine solution in presence of hydrochloric acid as mentioned in this paper.
TL;DR: The procedure cleanly affords acylsilanes in good yields and circumvents the use of stoichiometric copper(I) cyanide typically employed to synthesize these compounds from acid chlorides.
TL;DR: In this article, the crystal structures of H2L, and of two nickel(II) complexes 1 and 2 have been determined by single crystal X-ray diffraction using three different methods.
TL;DR: The preliminary mechanistic studies provided some insight regarding the key events in the proposed catalytic cycle, including beta-hydride elimination of an amido rhodium complex and carbometalation of the resulting imine.
Abstract: The development of a new chemical transformation, namely oxidative C-arylation of saturated (NH)-heterocycles, is described. This reaction combines dehydrogenation and arylation in one process, leading to cross-coupling of (NH)-heterocycles and haloarenes. Typical reaction conditions involve heating the reaction partners in anhydrous dioxane at 120−150 °C in the presence of RhCl(CO)[P(Fur)3]2 as the catalyst and Cs2CO3 as the base. Addition of tert-butylethylene as the hydrogen acceptor increases the chemical yield by diminishing the dehalogenation pathway. This method demonstrated a good substrate scope, allowing for cross-coupling of a variety of (NH)-heterocycles (e.g., pyrrolidine, piperidine, piperazine, morpholine) and halo(hetero)arenes to afford valuable heterocyclic products in one step. The preliminary mechanistic studies provided some insight regarding the key events in the proposed catalytic cycle, including β-hydride elimination of an amido rhodium complex and carbometalation of the resulting...
TL;DR: In this article, triphosphates of all four ribonucleoside derived morpholine subunits were synthesized and characterized by 1H and 31P NMR, UV and mass spectroscopy.
TL;DR: The methyl analogue of MRB has been radiolabeled with C-11 for studies of the NET system with positron emission tomography (PET) and used as precursors for radiosynthesis to prepare enantiomerically pure individual 11C-labeled MRB enantiomers for comparative PET studies in baboons.
TL;DR: In this article, a novel vic-dioxime, 1,2 dihydroxyimino-1-p-tolyl-3-aza-6-morpholine heptane (LH2) was prepared by reacting anti-ptolylschloroglyoxime with 4-(3-aminopropyl)morpholine in absolute THF.
Abstract: A novel vic-dioxime, 1,2 dihydroxyimino-1-p-tolyl-3-aza-6-morpholine heptane (LH2) was prepared by reacting anti-p-tolylchloroglyoxime with 4-(3-aminopropyl)morpholine in absolute THF. Mononuclear complexes with a metal–ligand ratio of 1:2 were prepared using CoII, CuII and NiII salts. The ligand and its complexes were characterized by elemental analyses, FT-IR, u.v.–vis., 1H- and 13C-n.m.r. spectra, magnetic susceptibility measurements, thermogravimetric analyses (t.g.a.), and by cyclic voltammetry.
TL;DR: In this article, the ECE mechanism of catechol in the presence of morpholine, dimethylamine, and diethylamine as nucleophile in aqueous solution was investigated.
Dissertation•
01 Jan 2004
TL;DR: A new series of 1-deoxy-1-[(6-(4-(substituted-aminosulfonyl)phenyl)amino)carbonylamino-9H-purin-9-yl]-N-ethyl-beta-D-ribofuranuronamides have been synthesized and tested at the human A3 adenosine receptor subtype, confirming that the p-sulfonamido moiety positively affected the activity of the molecules
Abstract: A new series of 1-deoxy-1-[(6-(4-(substituted-aminosulfonyl)phenyl)amino)carbonylamino-9H-purin-9-yl]-N-ethyl-β-d-ribofuranuronamides (83−102) have been synthesized and tested at the human A3 adenosine receptor subtype. All the derivatives described in this work displayed affinity versus this receptor in the nanomolar range and good selectivity versus A1 adenosine receptor subtype, confirming that the p-sulfonamido moiety positively affected the activity of the molecules. The best substituents at the sulfonamido nucleus were found to be small alkyl groups, like methyl, isopropyl, ethyl, or allyl moieties (compounds 96−100), whereas monosubstitution at the amino group led to a decrease in A3 affinity values. The selectivity versus A1 adenosine receptor subtype is increased when the amino group in the sulfonamido core is represented by a hydrogenated heterocyclic ring like piperidine, morpholine, or pyrroline. Bulky groups, like adamantane and alkyl chains with more than four carbon atoms, are detrimental f...
TL;DR: The first 4-enamine-N-methyl-1,8-naphthalimides (amine = piperidine, pyrrolidine, morpholine, Prn2NH, Pri2NH) were reported in this article.
Abstract: The first 4-enamine-N-methyl-1,8-naphthalimides (amine = piperidine, pyrrolidine, morpholine, Prn2NH, Pri2NH) are reported. The X-ray crystal structure of the piperidine derivative confirmed the E-stereochemistry and showed strong Π–Π stacking in the unit cell. The enamines are strongly fluorescent and quantum yields do not vary with the pKb of the amine. The solvent dependence of λ abs and λ flu is consistent with significant charge separation in the excited state.
Patent•
15 Oct 2004
TL;DR: In this article, the authors defined a general formula (I) for a compound having general activity as specific inhibitors of glyt1 and/or glyt2 transporters, where R represents a hydrogen atom or a vinyl group; n represents 0, 1 or 2; X represents a groups having formula CH or a nitrogen atom; R1 represents a phenyl or naphthyl group, or a cyclohexyl group or a heteroaryl group; R2 represents a gas atom, or one or more substituents selected from among the halogen atoms and the
Abstract: The invention relates to a compound having general formula (I), wherein: R represents a hydrogen atom or a vinyl group; n represents 0, 1 or 2; X represents a groups having formula CH or a nitrogen atom; R1 represents a phenyl or naphthyl group, or a cyclohexyl group, or a heteroaryl group; R2 represents a hydrogen atom, or one or more substituents selected from among the halogen atoms and the trifluoromethyl, alkyl, alkoxy, thienyl, phenyloxy, hydroxy, mercapto, thioalkyl, cyano groups or a group having general formula -NR4R5, SO2NR4R5, -SO2-alkyl, -SO2-phenyl, -CONR4R5, -COOR7, -CO-alkyl, -CO-phenyl, -NHCOR8, -NHSO2-alkyl, -NHSO2-phenyl and -NHSO2NR4R5 or a divalent group having formula -OCF2O-; and R4 and R5 each represent a hydrogen atom or an alkyl group or R4 and R5, together with the nitrogen atom bearing same, form a pyrrolidine, piperidine or morpholine ring. Compounds having formula (I) have a unique activity as specific inhibitors of glyt1 and/or glyt2 transporters.
TL;DR: In this article, the parent naphthoquinone was combined with the charge transfer complex between iodine and morpholine for the synthesis of 2-hydroxy-3-iodo-1,4-naphthoequinone.
TL;DR: A new series of monocyclic pseudopeptide tachykinin NK-2 receptor antagonists has been derived from the lead compound MEN11558, endowed with high in vivo potency at very low doses and long duration of action in animal models of bronchoconstriction.
Abstract: A new series of monocyclic pseudopeptide tachykinin NK-2 receptor antagonists has been derived from the lead compound MEN11558. A synthesis for these molecules sharing the same intermediate was designed and performed. The replacement of the succinic moiety with an aspartic acid and the functionalization of its amino group with a wide variety of substituents led to very potent and selective NK-2 antagonists. Best results were obtained through the insertion in position 12 of an amino group with R configuration, linked by a short spacer to a saturated nitrogen heterocycle (morpholine, piperidine, or piperazine). The study led to compounds 54 and 57, endowed with high in vivo potency at very low doses and long duration of action in animal models of bronchoconstriction. In particular 54 and 57 completely inhibited NK-2 agonist induced bronchoconstriction in guinea pig after intratracheal administration at subnanomolar doses (ED50 = 0.27 nmol/kg and 0.15 nmol/kg, respectively).
TL;DR: In this paper, nucleophilic reactions on cyanuric chloride were carried out under solvent free conditions to give 1,3,5 s-triazine derivatives with excellent yields, which were then used to obtain 1,5s triazine derivatives.
Abstract: Nucleophilic reactions on cyanuric chloride were carried out under solvent free conditions to give 1,3,5-s-triazine derivatives with excellent yields.
TL;DR: An efficient method for synthesis of oligonucleotide 2'-conjugates via amide bond formation on solid phase is described, well suited in principle for the preparation of peptide-oligonucleotide conjugates containing an amide linkage between the 2'-position of an oligon nucleotide and the N-terminus of a peptide.
Abstract: An efficient method for synthesis of oligonucleotide 2′-conjugates via amide bond formation on solid phase is described. Protected oligonucleotides containing a 2′-O-carboxymethyl group were obtained by use of a novel uridine 3′-phosphoramidite, where the carboxylic acid moiety was introduced as its allyl ester. This protecting group is stable to the conditions used in solid-phase oligonucleotide assembly, but easily removed by Pd(0) and morpholine treatment. 2′-O-Carboxymethylated oligonucleotides were then efficiently conjugated on a solid support under normal peptide coupling conditions to various amines or to the N-termini of small peptides to give products of high purity in good yield. The method is well suited in principle for the preparation of peptide–oligonucleotide conjugates containing an amide linkage between the 2′-position of an oligonucleotide and the N-terminus of a peptide.
TL;DR: In this article, the preparation of morpholine-2,3-diones and 2-hydroxymorpholin-3-ones from N-substituted β-amino alcohols is reported.
TL;DR: Some novel [1,2,4]triazolo[3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (ABG) compounds were prepared by heating 4-amino-5-aryl-1, 2, 4-triazole-3-thiones with different carboxylic acids in POCl3 as mentioned in this paper.
Abstract: Some novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazolylisoindole-1,3-dione 2a–c were prepared by heating 4-amino-5-aryl-1,2,4-triazole-3-thiones 1a–c with different (1,3-dioxo-1,3-dihydro-isoindol-2-yl) carboxylic acids in POCl3. Compounds 2a, b were hydrolyzed using HCl to yield [1,2,4]triazolo[3,4-b][1,3,4]thiadiazolyl-alkylamines 3a, b. Coupling 1a, c with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (ABG) afforded the corresponding S-glucosides 4a, b, which on oxidation with KMnO4 gave the corresponding sulfone 5. Treatment 1b, c with diphenyl diazomethane afforded benzhydrylsulfanyltriazolylamines 7a, b. 1,8-Bis-(4-chloro-phenyl)-bis[1,2,4]triazolo[3,4-c-,4′,3′-e][1,2,4,5]dithiadiazine 8 was formed by oxidation of 1b with lead tetracetate. Compound 1c reacted with morpholine in the presence of KI and I2 to give the triazolodisulfide 9 .
TL;DR: In this paper, a novel, stereoselective synthesis of the enantiomer of alcohol 5 is disclosed. The key steps of the synthesis include mercuric trifluoroacetate promoted regio-and stereose-lective hydration of an α,β-unsaturated ester, Frater-alkylation and use of morpholine derived amide for acylation.
TL;DR: The reaction of 4-hydroxycoumarin with some primary amines 2a-h and morpholine under microwave irradiation occurred without opening of the lactone ring to give N-substituted 4-aminocoumarins 3a-i in excellent yields.
Abstract: The reaction of 4-hydroxycoumarin (1) with some primary amines 2a-h and morpholine (2i) under microwave irradiation occurred without opening of the lactone ring to give N-substituted 4-aminocoumarins 3a-i in excellent yields. Under the same experimental conditions, 4-hydroxy-6-methyl-2-pyrone (4) reacted with benzylamine (2e) or 2-phenyl- ethylamine (2f) to give the corresponding N,N'-disubstituted 4-amino-6-methyl-2-pyridones 5e,f. The main advantages of this procedure are dramatically shortened reaction times, higher amine utilization and considerably improved yields.