Showing papers on "Morpholine published in 1996"

Kinetics of S-nitrosation of thiols in nitric oxide solutions.

Abstract: The S-nitroso adducts of nitric oxide (NO) may serve as carriers of NO and play a role in cell signaling and/or cytotoxicity. A quantitative understanding of the kinetics of S-nitrosothiol formation in solutions containing NO and O2 is important for understanding these roles of S-nitroso compounds in vivo. Rates of S-nitrosation in aqueous solutions were investigated for three thiols: glutathione, N-acetylcysteine, and N-acetylpenicillamine. Nitrous anhydride (N2O3), an intermediate in the formation of nitrite from NO and O2, is the most likely NO donor for N-nitrosation of amines as well as for S-nitrosation of thiols, at physiological pH. This motivated the use of a competitive kinetics approach, in which the rates of thiol nitrosation were compared with that of a secondary amine, morpholine. The kinetic studies were carried out with known amounts of NO and O2 in solutions containing one thiol (400 microM) and morpholine (200-5700 microM) in 0.01 M phosphate buffer at pH 7.4 and 23 degrees C. It was found that disulfide formation, transnitrosation reactions, and decomposition of the S-nitrosothiols was expressed as k7[N2O3][RSH], where RSH represents the thiol. The rate constant for S-nitrosation relative to that for N2O3 hydrolysis (k4) was found to be k7/k4 = (4.15 +/- 0.28) x 10(4), (2.11 +/- 0.11) x 10(4), and (0.48 +/- 0.04) x 10(4) M-1 for glutathione, N-acetylcysteine, and N-acetylpenicillamine, respectively. The overall (observed) rates of nitrosothiol formation reflect the fact that [N2O3] varies [NO]2[O2] and that [N2O3] also depends on [RSH] and the concentration of phosphate. Using a detailed kinetic model to account for these effects, the present results could be reconciled with apparently dissimilar findings reported previously by others.

Synthesis and Biological Activity of 3- and 5-Amino Derivatives of Pyridine-2-carboxaldehyde Thiosemicarbazone

Abstract: A series of 3- and 5-alkylamino derivatives, as well as other structurally modified analogues of pyridine-2-carboxaldehyde thiosemicarbazone, have been synthesized and evaluated as inhibitors of CDP reductase activity and for their cytotoxicity in vitro and antineoplastic activity in vivo against the L1210 leukemia. Alkylation of 3- and 5-amino-2-(1,3-dioxolan-2-yl)pyridines (1, 2) resulted in corresponding 3-methylamino, 5-methylamino, 3-allylamino, 5-ethylamino, 5-allylamino, 5-propylamino, and 5-butylamino derivatives (5, 6, and 11-15), which were then condensed with thiosemicarbazide to yield the respective thiosemicarbazones (7, 8, and 16-20). Oxidation of 3,5-dinitro-2-methylpyridine (21) with selenium dioxide, followed by treatment with ethylene glycol and p-toluenesulfonic acid, produced the cyclic ethylene acetal, 23. Oxidation of 2-(1,3-dioxolan-2-yl)-4-methyl-5-nitropyridine (26) with selenium dioxide, followed by sequential treatment with sodium borohydride, methanesulfonyl chloride, and morpholine afforded the morpholinomethyl derivative 30. Catalytic hydrogenation of 23 and 30 with Pd/C yielded the corresponding amino derivatives 24 and 31. Catalytic hydrogenation of 5-cyano-2-methylpyridine (33) with Raney nickel, followed by treatment with acetic anhydride, gave the amide derivative 35. N-Oxidation of 35, followed by rearrangement with acetic anhydride, produced the acetate derivative, 5-[(acetylamino)methyl]-2-(acetoxymethyl)pyridine (37). Repetition of the N-oxidation and rearrangement procedures with compound 37 yielded the diacetate derivative 39. Condensation of compounds 24, 31, and 39 with thiosemicarbazide afforded the respective 3,5-diaminopyridine-, 4-(4-morpholinylmethyl)-5-aminopyridine-, and 5-(aminomethyl)pyridine-2-carboxaldehyde thiosemicarbazones (25, 32, and 40). The most biologically active compounds synthesized were the 5-(methylamino)-, 5-(ethylamino)-, and 5-(allylamino)pyridine-2-carboxaldehyde thiosemicarbazones (8, 17, and 18), which were potent inhibitors of ribonucleotide reductase activity with corresponding IC50 values of 1.3, 1.0, and 1.4 microM and which produced significant prolongation of the survival time of L1210 leukemia-bearing mice, with corresponding optimum % T/C values of 223, 204, and 215 being obtained when administered twice daily for six consecutive days at dosages of 60, 80, and 80 mg/kg, respectively.

Systematic investigations on the reactivity of oxazolinium salts

Abstract: The termination reaction of the cationic polymerization of 2-phenyl- and 2-nonyl-2-oxazolines was examined by reacting the corresponding model oxazolinium salts having tosylate and trifluoromethansulfonate counterions with various nucleophiles. The reaction was monitored by 1 H NMR spectroscopy. Piperidine and KOH react with the oxazolinium salts very fast and quantitatively. In the case of piperidine, the use of a double molar amount of piperidine is necessary to achieve complete conversion. The addition of piperidine, pyridine, 4-dimethylaminopyridine and morpholine takes place in position 5 of the oxazolinium ring, whereas water and KOH add in position 2. The rate of the termination reaction depends on the electron density of the nucleophile which can be correlated with the pK a value. With CF 3 SO 3 - as counterion the addition of nucleophiles in position 5 is distinctly faster, whereas the addition of water in position 2 is much slower than with TsO - as counterion. The ring-opening of the nonyl oxazolinium ion is slower than that of the phenyl oxazolinium ion.

Further Studies on the Buffer-Catalyzed Cleavage and Isomerization of Uridyluridine. Medium and Ionic Strength Effects on Catalysis by Morpholine, Imidazole, and Acetate Buffers Help Clarify the Mechanisms Involved and Their Relationship to the Mechanism Used by the Enzyme Ribonuclease and by a Ribonuclease Mimic

Abstract: The cleavage and isomerization of 3‘,5‘-uridyluridine catalyzed by morpholine buffers and by imidazole buffers has been reinvestigated. The key evidence for a previously proposed partitioning mechanismin which the buffer acid BH+ converts the substrate to a phosphorane monoanion intermediate which then partitions either to the 2‘,5‘ isomer of the substrate or (with buffer base catalysis) to the cleavage productis confirmed. The negative catalytic effect of the buffer base on the isomerization reaction is not due to a medium effect. Indeed the medium effect on this reaction is in the opposite direction, strengthening the catalytic evidence. However, this branching mechanism with sequential bifunctional catalysis of the cleavage reaction is accompanied by an additional cleavage path using the buffer base only. This additional path, for which several alternative mechanisms are possible, is required by the results of improved studies on the imidazole catalysis. These show that the previously reported decrease...

Palladium-Catalyzed Double and Single Carbonylations of β-Amino Alcohols. Selective Synthesis of Morpholine-2,3-diones and Oxazolidin-2-ones and Applications for Synthesis of α-Oxo Carboxylic Acids

Abstract: Catalytic cross double carbonylation of secondary amines and alcohols proceeds in the presence of [PdCl2(MeCN)2] and CuI under carbon monoxide (80 atm) and oxygen (5 atm). Catalytic intramolecular double carbonylation of β-amino alcohols gives morpholine-2,3-diones, which are excellent protecting compounds of amino alcohols and important precursors for biologically active nitrogen compounds. In contrast, catalytic single carbonylation of β-amino alcohols under a mixture (1 : 1) of carbon monoxide and oxygen (1.0 atm) proceeds to give oxazolidin-2-ones selectively. The reaction can be explained by assuming a mechanism which includes intramolecular nucleophilic attack of the hydroxy group of (hydroxyethyl)aminocarbonyl ligands on the CO ligand of the carbamoylpalladium(II) complexes, followed by reductive elimination to give morpholine-2,3-diones. In contrast, direct nucleophilic attack of the hydroxy group to the carbamoyl group affords oxazolidin-2-ones. As a common intermediate for the double and single ...

N-oxides of morpholine derivatives and their use as therapeutic agents

Abstract: ##STR1## The present invention relates to morpholine derivatives of the formula (I) and pharmaceutically acceptable salts thereof wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9a , R 9b , X, Y, Z and Het are as defined in the specification; m is 0 or 1; and n is 0 or 1, where the sum total of n+m is 1 or 2. The compounds are of particular use in the treatment of pain, inflammation, migraine, emesis and postherpetic neuralgia.

Chemical origin of high activity in oxygenation of cyclohexane by H2O2 catalysed by dinuclear iron(III) complexes with amide-containing ligands

Abstract: The crystal structures of two dinuclear iron(III) complexes containing an oxo bridge, [Fe2OCl2L2][ClO4]2·2H2O 1[L =N,N-bis(2-pyridylmethyl)glycinamide] and [Fe2OCl2L2][ClO4]22(L =N-{2-[bis(2-pyridylmethyl)amino]ethyl}morpholine) were determined. Their structural features are quite similar to those of the corresponding linear dinuclear complex [Fe2OCl2(tpa)2][ClO4]2, where tpa is tris(2-pyridylmethyl)amine; the ligands act as tetradentate tripods, and the Fe–O (amide) and average Fe–N (morpholine) distances are 2.165(6) and 2.45(1)A, respectively. Complex 1 exhibited much higher activity for the hydroxylation of cyclohexane in the presence of H2O2, while the activities of the other two complexes are negligible. In contrast, all three complexes exhibited high activity for the decomposition of H2O2. These results indicate that the active species for oxygenation of cyclohexane, which may be an iron(III)–peroxide adduct (I), should be different from that for decomposition of H2O2, adduct II, and that these two species may exist in the solution of complex 1. It is postulated that adduct I may be a dinuclear iron(III)–η1-hydroperoxide species stabilized through hydrogen bonding between the hydroperoxide ion and the oxygen atom of the amide group. Extended-Huckel molecular orbital calculations showed that the hydrogen bonding may lead to induction of high ‘oxo-like’ activity in the peroxide adduct. In the cases of the tpa and morpholine complexes the formation of a η1-hydroperoxide adduct seems unfavourable because of both steric and electronic reasons; instead a (µ-η1:η1-peroxo)diiron(III) species, adduct II, is formed which induces high catalase-like activity.

Kinetics of Proton Transfer from 2-Nitro-4-X-phenylacetonitriles to Piperidine and Morpholine in Aqueous Me2SO. Solvent and Substituent Effects on Intrinsic Rate Constants. Transition State Imbalances

Abstract: Rate constants ( ) for the deprotonation of 2-nitro-4-X-phenylacetonitrile, 2-X (X = NO2, SO2CH3, CN, CF3, Br, and Cl) by piperidine and morpholine and for the reverse reaction ( ) have been determined in 90% Me2SO−10% water, 50% Me2SO−50% water, and water (X = NO2, SO2CH3, CN only). Bronsted βB values (dlog /dp ), Bronsted αCH values (dlog /dlog ), and intrinsic rate constants (log ko = log(k1/q) for p − p + log(p/q) = 0) were calculated from these data. αCH is smaller than βB, implying an imbalance which is consistent with a transition state in which delocalization of the negative charge into the 2-nitrophenyl moiety lags behind proton transfer. A consequence of this imbalance is that the intrinsic rate constant decreases with increasing electron withdrawing strength of X. For π-acceptor substituents (NO2, SO2CH3, CN) there is a further decrease in ko due to a lag in the delocalization of the charge into X. The intrinsic rate constants depend very little on the Me2SO content of the solvent which is show...

Enantioselective synthesis of (R)-and (S)-α-aminoacids using (6S)- and (6R)-6-methyl-morpholine-2,5-dione derivatives

Abstract: The alkylation of both 3 and 4 gives exclusively the trans derivatives 5 and 6 , respectively, with >98% diastereoselectivity. Cleavage of the morpholine-2,5-dione ring of 5 and 6 leads to enantiomerically pure ( S )- and ( R )-α-aminoacids, respectively. The configurations of stereogenic centers introduced on 3, 4, 5 and 6 have been assigned on the basis of the 1 H-NMR data, conformational analysis and nOe measurements.

Determination of aliphatic and alicyclic amines in water by gas and liquid chromatography after derivatization by chloroformates.

Abstract: Two new methods were developed for the analysis of aliphatic (n-propylamine, pentylamine, hexylamine, heptylamine, octylamine) and alicyclic (pyrrolidine, morpholine, piperidine, piperazine) amines in water samples after derivatization and liquid-liquid-extraction. The carbamate-derivatives formed were determined by GC/MS (trichloroethyl carbamates) as well as by HPLC/fluorescence detection (9-fluorenylmethyl carbamates) in a concentration range between 0.05 and 1.0 μg/l suitable for drinking water analysis. Applications to German rivers and sewage plants show that both new methods produce corresponding results in analysing aliphatic and alicyclic amines in surface waters as well as in waste water samples.

Some 3-hydrazono-2-indolinones and N-Mannich bases as potential anticonvulsants

Abstract: In this study a new series of 3-aryloxy/arylthioxyacetylhydrazono-2-indolinones obtained by condensation of isatin with aryloxy/arythioxyacetylhydrazines were treated with morpholine and formaldehyde to yield 1-morpholinomethyl-3-aryloxy/arylthioxyacetylhydrazono-2- indolinones. Structures of all the compounds were assigned on the basis of spectral data (UV, IR, 1H-NMR, EIMS) and elemental analyses. Anticonvulsant evaluation of the compounds revealed varying degrees of activity against pentylenentetrazole induced seizures.

Photochromism of spironaphthooxazines having electron-donor substituents

Abstract: Spectral and photochromic properties of spironaphthooxazines (SNOs) with piperidine and morpholine substituents have been studied at different temperatures in various solvents. It has been recognized that introduction of these substituents in naphthooxazine fragment leads to fluorescence of the initial form of SNO molecules at low temperatures, which disappears with temperature rise. The dependences of the photoinduced form in non-polar solvents. It is proposed that the coloured form of substituted SNOs has a bipolar structure with a positive charge on piperidine or morpholine nitrogen atom contrary to the quinonoic form of unsubstituted SNO.

The utilization of morpholine as a sole nitrogen source by Gram-negative bacteria

Abstract: The ability of Gram-negative bacteria to degrade morpholine when growing in pure culture is reported for the first time. Several bacterial strains were able to degrade morpholine and to utilize it as a sole nitrogen source but not as a sole carbon and energy source. The organisms studied were obtained from river water and activated sludge and could not be isolated directly on morpholine-containing media which always yielded growth of Gram-positive bacteria using morpholine as a carbon and energy source. The Gram-negative strains were isolated on the basis of their ability to grow on the structurally-related heterocyclic amines piperidine and pyrrolidine.

Cyanogen bromide-induced chemical ligation: Mechanism and optimization of the reaction conditions

Abstract: Chemical ligation induced by BrCN in the presence of N-substituted morpholine has been studied in details. It has also been shown that the phosphate activation by BrCN can be used for the synthesis of nucleotide derivatives in aqueous solutions.

Influence of Microwaves Irradiation on Modification of Oxetane Based Polymers with 4-(2-Amino-ethyl)morpholine

Abstract: Influence of Microwaves Irradiation on Modification of Oxetane Based Polymers with 4-(2-Amino-ethyl)morpholine

Water-based detergent composition

Abstract: PURPOSE: To obtain the subject composition efficiently removing dirts on the solid surfaces of precise part items or tools used for their assembling process without corroding metals or alloys contained in the material or the tools by including a carbonate of a specific amine-based compound. CONSTITUTION: This composition contains carbonate of an amine-based compound having an N-atom number of 1-5 and a molecular weight of 50-300 (preferably monoethanolamine, morpholine or diaminopropane, etc.) preferably in an amount of 0.1-50wt.%. Preferably, 10-70wt.% alkylene oxide compound selected from formulae I-III (R is a 1-8C hydrocarbon; R and R are each a 2-4C alkylene; X is H or a 1-4C alkyl, etc.; (m) is 1-7; (n) is 0-7; (p) and (q) are each 0-5) is further mixed in the composition to improve detergency. As the alkylene oxide compound, ethylene glycol dimethyl ether or propylene glycol diacetate, etc., is preferable.

Anti-Inflammatory Drugs. III. Salts of Diclofenac with N-(2-Hydroxyethyl)- piperidine, N-(2-Hydroxyethyl)morpholine and N-(2-Hydroxyethyl)piperazine

Abstract: The molecular and crystal structures of three salts of the same anion, N-(2-hydroxyethyl)piperidinium 2-(2,6-dichlorophenylamino)phenylacetate, C 7 H 16 NO + .C 14 H 10 Cl 2 NO 2 - , N-(2-hydroxyethyl)morpholinium 2-(2,6-dichlorophenylamino)phenylacetate, C 6 H 14 NO 2 + .C 14 H 10 Cl 2 NO 2 - , N-(2-hydroxyethyl)piperazinium 2-(2,6-dichlorophenylamino)phenylacetate, C 6 H 15 N 2 O + .C 14 H 10 Cl 2 NO 2 - , have been determined by X-ray diffraction. Strong anion-cation interactions via hydrogen bonds are the prime driving force for crystal self-assembly. Packing is determined by weak hydrogen-bonding interactions (C-H...O and C-H...Cl). The three compounds are isomorphous and are characterized by the same network of hydrogen bonds. Structural results are related to the different solubilities of the three salts.

3,4-Dimethoxy cinnamic acid tertiary amides: synthesis and evaluation of antiinflammatory and analgesic activities.

Abstract: In this study, eight compounds with cinnamoyl amide structure have been synthesized by dicyclohexylcarbodiimide/hydroxybenzotriazol method. The structures of the compounds were elucidated by UV, IR, 1H-NMR, mass spectroscopy and the elementary analysis. The antiinflammatory activities of the synthesized compounds were determined by carrageenan-induced hind paw edema test in mice and the most active compounds were found to be the dimethyl, diethyl and morpholine amide derivatives. Analgesic activities were determined by the modified "Koster" test; diisopentyl and morpholine amide derivatives have shown the highest activity.

Fungicidal mixtures of an oxime ether carboxylic acid amide with a morpholine or piperidine derivative

Abstract: The invention concerns a fungicidal mixture containing: a) an oxime ether carboxylic acid amide of formula (I), in which R stands for hydrogen or halogen; and b) a morpholine derivative (II) selected from the group comprising compounds (IIa), (IIb) and (IIc) [N=10,11,12 (60-70 %) or 13] in a synergistically active amount.