Showing papers on "Morpholine published in 2008"

Morpholine-based immonium and halogenoamidinium salts as coupling reagents in Peptide synthesis1.

Abstract: Here we describe a new family of N-form immonium-type coupling reagents that differ in their carbocation skeleton structure. The N-methylpiperazine derivative failed to form immonium salts, while the thiomorpholine derivative did not give better results than the coupling reagents currently used. The presence of the morpholine had a marked influence on the solubility and stability as well as the reactivity of the reagent. Finally, the fluoroamidinium salt performed extremely well in the presence of only 1 equiv of base, thereby confirming the effect of the proton acceptor in the reaction.

RAFT Homo- and Copolymerization of N-Acryloyl-morpholine, Piperidine, and Azocane and Their Self-Assembled Structures

Abstract: We present new polymeric amphiphiles derived from N-acryloyl derivatives of the cyclic secondary amines: morpholine, piperidine, and azocane polymerized by reversible addition−fragmentation transfer (RAFT) polymerization. Both homopolymerization and block copolymerization of N-acryloylmorpholine (AM), N-acryloylpiperidine (AP), and N-acryloylazocane (AH) were carried out. The block copolymeric amphiphiles, poly[(N-acryloylmorpholine)-block-(N-acryloylpiperidine)] (PAM-PAP) and poly[(N-acryloylmorpholine)-block-(N-acryloylazocane)] (PAM-PAH) were investigated, PAM being a hydrophile, and PAP and PAH being hydrophobes. Moreover, to compare PAM as a hydrophilic block with poly(ethylene glycol) (PEG), poly[(ethylene glycol)-block-(N-acryloylpiperidine)] (PEG-PAP) was also formed. In all cases, the degree of polymerization was well-controlled and polymers were obtained in monomodal distributions. The macroamphiphile aggregates in water were reproducibly well-formed by dialysis with a size range between 10 and...

Asymmetric hydroamination of acrylonitrile derivatives catalyzed by Ni(II)-complexes

Abstract: Chiral ferrocenyl tridentate phosphine ligands were synthesized and used in asymmetric hydroamination reactions catalyzed by Ni(II)-complexes. Compounds of the type [Ni(PPP)L]2+, where L is a chloride, solvent molecule or a coordinated substrate, were isolated. The efficiency of these complexes in asymmetric catalysis was high when aliphatic or aromatic amines were reacted with electron-poor olefins, especially with acrylonitrile derivatives. This hydroamination reaction affords up to 95% enantioselectivity at −80 °C for the addition of morpholine to methacrylonitrile (69% ee at room temperature).

1H, 13C, and 15N solid-state NMR studies of imidazole- and morpholine-based model compounds possessing halogen and hydrogen bonding capabilities

Abstract: The halogen and hydrogen bonding interactions present in solid 1-(2,3,3-triiodoallyl)imidazole (1), morpholinium iodide (2), the 1:1 cocrystal 1-(2,3,3-triiodoallyl)imidazole·morpholinium iodide (3), morpholine (4), imidazole (5), and 1-(3-iodopropargyl)imidazole (6) have been investigated by solid-state 1H, 13C, and 15N NMR spectroscopies. Comparison of the 15N CP MAS NMR spectrum of 3 with that of 2 indicates that protonated morpholine is present in solid 3, but this conclusion must be taken with caution as GIPAW calculations predict a 15N chemical shift for morpholine similar to that of the morpholinium cation. Conclusive evidence for the presence of a morpholinium cation in crystalline 3 was obtained by recording the static 15N NMR spectrum of this host−guest complex and comparing the morpholinium/morpholine part of the spectrum with the static spectra of 3 and 4 as obtained from ab initio calculations of NMR parameters based on the X-ray structures of these compounds. Concerning the imidazolyl group,...

Synthesis of medicinally interesting polyfluoro ketones via perfluoroalkyl lithium reagents.

Abstract: The addition of (pentafluoroethyl)- and (heptafluoropropyl)lithium to various acyl derivatives was studied. Weinreb and morpholine amides led to polyfluoro ketones in high to quantitative yields in short reaction times. Derivatives of 2-fluorocarboxylic acids may produce 1,1,1,2,2,4-hexafluoro ketones and 1,1,1,2,2,3,3,5-octafluoro ketones. The methodology can provide inhibitors for various lipolytic enzymes, including phospholipase A2.

Synthesis and biological activity of functionalized indole-2-carboxylates, triazino- and pyridazino-indoles.

Abstract: Condensation of aryl hydrazines with ethyl pyruvate gave the respective hydrazones 4-6; Fischer indolization led to substituted-1H-indole-2-carboxylic acid ethyl esters 7-9. The Mannich reaction of these compounds with formaldehyde and morpholine yielded ethyl 3-(morpholinomethyl)-substituted-1H-indole-2-carboxylates 10-12. The 5,7-dichloro-1H-indole-2-carbohydrazide 13 was cyclized with methyl orthoformate in DMF to give 6,8-dichloro[1,2,4]triazino[4,5-a]indol-1(2H)-one 14. Vilsmeier-Haack formylation of 7-9 gave ethyl 3-formyl-substituted-1H-indole-2-carboxylates 15-17 whose 2,2'-((5-chloro-2-(ethoxycarbonyl)-1H-indol-3-yl)methylene)bis-(sulfanediyl) diacetic acid 18 was prepared. The reaction of 15 and 16 with substituted anilines by conventional and microwave methods gave ethyl 3-(N-aryliminomethyl)-5-halo-1H-indole-2-carboxylates 19-29. In a cyclocondensation reaction of 19-25 with thiolactic acid or thioglycolic acid substituted indolylthiazolidinones 30-33 were prepared. Reaction of hydrazine hydrate with 15-17 did not give the respective hydrazones but directly led to the cyclized products substituted-3H-pyridazino[4,5-b]indol-4(5H)-ones 34-36, while a reaction with 2,4-dichlorophenylhydrazine yielded the uncyclized hydrazones. The chlorination of 35 and 36 with POCl3 gave pyridazino[4,5-b]indoles 39 and 40, respectively; reaction of the latter compounds with morpholine gave 4-(substituted-5H-pyridazino[4,5-b]indol-4-yl)morpholine 41 and 42. Mannich reaction of 34 with formaldehyde and N-ethylpiperazine gave 8-chloro-3-((4-ethylpiperazin-1-yl)methyl)-3H-pyridazino[4,5-b]indol-4(5H)-one 43. The microwave assistance of selected reactions has a profound effect on the reaction speed. The structures of the new compounds were confirmed by both analytical and spectral data. Some compounds were subjected to investigations concerning their antimicrobial, tranquilizing, and anticonvulsant activities.

Electrochemical Oxidation of Dopamine in the Presence of Secondary Amine. An Alternative Way for Quantitative Dopamine Determination at a Gold Electrode

Abstract: Electrooxidation of dopamine in the absence and presence of morpholine as a nucleophile was investigated on a gold electrode in phosphate buffer, pH 7. The results have shown that electrochemically produced dopaminoquinone undergoes an attack by morpholine via 1,4-Michael addition. The reaction products have been identified by electrospray ionization mass spectrometry (ESI-MS). The procedure used is suitable for quantitative dopamine determination in the presence of the ascorbic acid excess at a unmodified gold electrode.

Bis-morpholine-Substituted Perylene Bisimides: Impact of Isomeric Arrangement on Electrochemical and Spectroelectrochemical Properties

Abstract: The synthesis and separation of the 1,6- and 1,7- isomers of N,N′-bis(n-butyl)dimorpholino-3,4:9,10-perylenetetracarboxylic acid bisimide are reported. Investigations of the electrochemical and spectroscopic, in particular, spectroelectrochemical, properties of the two isomers reveal a sequence of electrochemically and chemically reversible redox processes for both isomers. Importantly, the 1,7-isomer of N,N′-bis(n-butyl)dimorpholino-3,4:9,10-perylenetetracarboxylic acid bisimide was observed to undergo a two-electron oxidation process, which contrasts with the behavior of both the corresponding 1,6-isomer and other related amino-substituted perylene bis-imide species.

New stimuli-responsive polymers derived from morpholine and pyrrolidine

Abstract: The preparation of three new ionizable monomers: N-ethyl morpholine metacrylate (EMM), N-ethyl morpholine methacrylamide (EMA) and N-ethyl pyrrolidine metacrylamide (EPA) and their respective homopolymers poly-EMM, poly-EMA and poly-EPA prepared by radical polymerization in solution, is described. The systems have been characterized by NMR and FTIR spectroscopic techniques, determined their glass transition temperatures by DSC and their respective pKs. Moreover, crosslinked samples were prepared by bulk polymerization using N,N-methylene bisacrylamide (BAam) and the trifunctional 1,3,5-triacryloylhexa-hydro-1,3,5-triazine (135-T) as crosslinkers. The studies of swelling kinetics were carried out in different pH buffer solutions (2, 7.4 and 10) in a thermostatic bath at 37 °C showing hydration degrees that go from 2,600% to about 200% depending on the pH and on the crosslinker used. The systems seem to be suitable for the preparation of smart hydrogels for drug delivery and Tissue Engineering.

Thermal analysis of 2-oxocyclopentanedithiocarboxylato complexes of iron(iii), copper(ii) and zinc(ii) containing pyridine or morpholine as the second ligand

Abstract: A series of ternary complexes of the types M2L′2L″2;ML′2L″2 (M=Fe, Cu, Zn; L′=2-oxocyclopentane dithiocarboxylate; L″=pyridine, morpholine) and CuL′2H2O was prepared afresh. Except the iron complex, all are dimer and complexation is through the dithio moiety of the ligand L′. Their thermal decomposition was carried out in air at heating rate 10°C min−1 and it revealed that the dehydration of the aqua complex follows the same path as the carboxylates and the pyridine complexes have the tendency to follow one-step decomposition. The copper complexes are less thermally stable. The overall thermal stability of the 2-oxocyclopentanedithiocarboxylato complexes of the three metals with the volatile ligands was found to be in the order: (CuLmorph)2< CuL2H2O<(CuLpy)2<(ZnLmorph)2<(ZnLpy)2

Sampling and analytical methodology development for the determination of primary and secondary low molecular weight amines in ambient air.

Abstract: In this project, a sampling device and an analytical method have been developed to simultaneously analyse the most frequently found low molecular weight amines, including aliphatic, aromatic and alcohol amines. These amines are diethanolamine, ethanolamine, methylamine, isopropylamine, morpholine, dimethylamine, and aniline. A sampling device was developed using a 37 mm cassette with glass fibre filters impregnated with sulfuric acid. Immediately after sampling, the filter was transferred to vials containing a solution of dansyl chloride. Dansyl chloride was used for derivatisation because it forms aromatic sulfonamides that are fluorescent and easy to protonate for MS detection. The effect of using an internal standard made with the dansylated derivative of 1-(2-methoxyphenyl)piperazine (MOPIP) on the uncertainty and efficiency of the method was also evaluated. This internal standard was spiked directly onto filters. The coupling of HPLC/ESI-MS was used for the simultaneous analysis of all the derivatives. This method showed detection limits of about 0.03 microg mL(-1) to 0.3 microg mL(-1) of amine with an average expanded uncertainty of 3% to 6% depending on the amine. The methodology recoveries are close to 100% for all the amines, and the overall estimated expanded uncertainties vary between 10% and 13% depending on the amine. This new strategy will be useful in evaluating workplace air since a unique sampling system will be used, independent of the amine to be quantified.

o-Carboxybenzoylferrocene. Bioactivity and chemical Modifications

Abstract: The antitumor activity of o-carboxybenzoylferrocene sodium salt (1) was studied in vivo. Interaction between o-carboxybenzoylferrocene (2) and N,N′-carbonyldiimidazole in boiling methylene dichloride leads to 3-(N-imidazolyl)-3-ferrocenylisobenzofuran-1(3H)-one (5). The structure of compound 5 was established by X-ray analysis. Aminolysis of compound 5 in toluene gave rise to ferrocenoylbenzamides (6a–d)–derivatives of dimethylamine, piperidine, pyrrolidine and morpholine. Copyright © 2008 John Wiley & Sons, Ltd.

Synthesis of 4-alkyl(aryl, hetaryl)-2-thioxo-5,6,7,8-tetrahydroquinoline-3-carbonitriles and their derivatives by cross-recyclization of 4-alkyl(aryl, hetaryl)-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 4-(cyclohex-1-en-1-yl)-morpholine, alkyl halides, and cyclohexanone

Abstract: Cross recyclization of 4-substituted 2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 4-(cyclohex-1-en-1-yl)morpholine, alkyl halides, and cyclohexanone gave the corresponding substituted 2-thioxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonitriles, 2-alkylsulfanyl-5,6,7,8-tetrahydroquinoline-3-carbonitriles, 3-amino-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamides, and 4-oxo-2,2-pentamethylene-1,2,3,4,7,8,9,10-octahydropyrimido[4′,5′:4,5]thieno[2,3-b]quinolines. The structure of 3-(4-bromophenyl)-2,2-pentamethylene-11-(2-thienyl)-1,2,3,4,7,8,9,10-octahydropyrimido[4′,5′:4,5]thieno[2,3-b]quinoline was proved by X-ray analysis.

Palladium-catalyzed aminations of aryl halides with phosphine-functionalized imidazolium ligands

Abstract: A series of 1-(2-diphenylphosphinoferrocenyl)ethyl-3-substituted imidazolium iodides [3-substituent = methyl (1a); isopropyl (1b); tert-butyl (1c); 1-adenosyl (1d); cyclohexyl (1e); 2,6-dimethylphenyl (1f); 2,4,6-trimethylphenyl (1g); 2,6-diisopropylphenyl (1h)] have been prepared and evaluated as ligands in the palladium-catalyzed aminations of aryl halides with various amines. The scope of the coupling process was carried out for various aryl bromides and chlorides with the catalysts generated in situ from a mixture of Pd(OAc)2 and 1 in the presence of a base. NaOtBu was found the choice of base in combination with dioxane, toluene, or DME as solvent, although NaOH or Cs2CO3 promoted the coupling of 4-bromotoluene with morpholine in moderate conversion. The steric hindrance from the 3-substituent of imidazolium in the hybrid-bidentate chelating system was found to be only beneficial to the substrates without ortho-substituents. The more sterically hindered 1d or 1h promoted the coupling of bromobenzene with morpholine in nearly quantitative conversion with 0.2 mol% of palladium loading in the presence of NaOtBu at 110 °C, and 94% of conversion was afforded with the less sterical demanding 1a for a longer time. However, for the substrates with ortho-substituents, higher conversions were achieved with 1a. The Pd(OAc)2/1dcatalytic system was also active for deactivated aryl chloride, and 71% isolated yield for the desired product was realized for coupling of 4-chloroanisole with morpholine at 2 mol% of catalyst loading. The developed catalyst system has been applied successfully to the synthesis of a key building block for a type of functional polymers.

Michael reactions of titanium enolates of glycolic acid derivatives with the Weinreb and morpholine amides of acrylic acid.

Abstract: The conjugate additions of titanium enolates of glycolate-derived chiral oxazolidin-2-ones to various Michael acceptors have been evaluated as an entry to enantiopure 1,2,5-trioxygenated and related synthons α,β-unsaturated Weinreb and morpholine amides do react under suitable conditions and their adducts can be converted to diverse C1−C5 chiral fragments

Controlled photochemical reaction of 4-oxo(phenylacetyl)morpholine and 1-(phenylglyoxylyl)piperidine in solid supramolecular systems

Abstract: Six inclusion compounds containing a photoreactive guest molecule, 4-oxo(phenylacetyl)morpholine or 1-(phenylglyoxylyl)piperidine, with different host molecules have been crystallized. The guest molecules underwent photochemical reaction upon irradiation. Examining their structures suggests that γ-hydrogen abstraction by an oxygen, the first step in cyclization of α-oxoamides, should be possible in all cases. In four cases crystallinity was maintained during and at the end of the conversion process i.e. the process was a single-crystal to single-crystal transformation. The crystal structure of the product crystals revealed that in two of the inclusion compounds the product obtained is a result of enclosure to a four-membered ring while in the other two the product obtained results from enclosure to a five-membered ring. The morpholine molecules adopt two different conformations. The photochemical reaction may take different courses either as a result of the different conformation or as a result of the different shapes of the cavities provided by the host molecules.

Fungicidal composition and method for controlling noxious fungi

Abstract: A fungicidal composition is provided. A fungicidal composition comprising synergistically effective amounts of (a) a carboxylic acid amide derivative of the formula (I) or its salt: wherein B is a heterocyclic group which may be substituted; each of R1 and R2 which are independent of each other, is alkyl; X is halogen, alkyl or alkoxy; and n is an integer of from 0 to 5, and (b) at least one fungicidal compound selected from the group consisting of an azole compound, an anilinopyrimidine compound, a triazolopyrimidine compound, a strobilurin compound, an N-halogenothioalkyl compound, a pyridinamine compound, a bicarbonate, an inorganic sulfur compound, a dithiocarbamate compound, an organic chlorine compound, a dicarboxyimide compound, an amine compound, a phenylpyrrole compound, a benzophenone compound, a dinitrobenzene compound, a piperidine compound, a morpholine compound, etc.