Showing papers on "Morpholine published in 1992"

1,2,3-Trisubstituted cyclopropanes as conformationally restricted peptide isosteres : application to the design and synthesis of novel renin inhibitors

Abstract: The 1,2,3-trisubstituted cyclopropanes 6 and 7 are the first members of a novel class of isosteric replacements for peptide linkages that are more generally represented by the dipeptide mimics 2 and 3. These unique peptide surrogates are specifically designed to lock a section of a peptide backbone in an extended beta-strand conformation (phi-angle restriction) while simultaneously enforcing one of two specifically defined orientations for the amino acid side chain (chi 1-angle restriction). Methods were first developed for the stereoselective, asymmetric synthesis of the trisubstituted cyclopropanes 15a-d, 18a-d, 22a-d, and 23a-d (Scheme II), by an efficient approach featuring the Rh2(S-MEPY)4 (11) and Rh2(R-MEPY)4 (20) catalyzed cyclization of the allylic diazoacetates 10a-d to give the optically active lactones 12a-d and 21a-d, respectively, in up to greater than or equal to 94% enantiomeric excess. Nucleophilic opening of the lactone ring of 12a-d gave the corresponding morpholine amides 14a-d. By exploiting tactics that allowed for selective epimerization of one of the two functionalized side chains on the cyclopropane nucleus, 14a-d were transformed into the two series of diastereoisomeric morpholine amide carboxylic acids 15a-d and 18a-d. Epimerization of the morpholine amide group on 14a-d followed by Jones oxidation of the intermediate alcohols gave 15a-d. Alternatively, initial oxidation of the primary alcohol groups in 14a-d followed by selective, base-catalyzed inversion alpha to the aldehyde function and then Jones oxidation gave the diastereomeric dicarboxylic acid derivatives 18a-d. In a similar fashion, the enantiomeric lactones 21a-d were converted into the two corresponding enantiomeric series of dicarboxylic acid derivatives 22a-d and 23a-d. Inhibitors of aspartic proteinases, of which renin is a typical example, are known to bind to the enzyme active site cleft in an extended conformation. Thus, in order to evaluate the efficacy of 1,2,3-trisubstituted cyclopropanes as rigid replacements of beta-strand secondary structure in pseudopeptidic ligands, 15a-d, 18a-d, 22a-d, and 23a-d were incorporated at the P3 subsite of the potential renin inhibitors 24a-h and 25a-h by coupling with the tripeptide replacement 8. A significant number of substances inhibited renin at nanomolar concentrations. On the basis of this preliminary test, 1,2,3-trisubstituted cyclopropanes do appear to constitute a viable new class of peptide mimics. Since the stereochemistry at each carbon on the cyclopropane ring may be altered, these novel replacements may also function as stereochemical probes to establish the conformation of pseudopeptide ligands bound to their macromolecular targets.

New naphthalimides, toners containing these and the use of the new naphthalimides as additives for toners

Abstract: New naphthalimides, useful as additives in toners for controlling the charge and conductivity, of the formula ##STR1## in which R represents C 1 - to C 22 -alkyl, R 1 and R 2 independently of one another in each case represent C 1 - to C 4 -alkyl, or R 1 and R 2 , together with the nitrogen atom in between, form a pyrrolidine, piperidine or morpholine ring, n represents 2 or 3 and Xsup⊖ represent one equivalent of a benzoate or naphthoate, which is optionally substituted by chlorine, bromine, methyl, methoxy, hydroxyl, cyano and/or hydroxycarbonyl, of a benzenesulphonate which is substituted by hydroxyl, amino or nitro, of a naphthalenesulphonate which is optionally substituted by hydroxyl, amino or a sulphonic acid group, or of a fluorine-substituted anion of a C 4 - to C 18 -alkanecarboxylic or -alkanesulphonic acid

Process of making regenerated cellulose articles

Abstract: Aqueous solutions of an amine N-oxide such as N-methyl morpholine N-oxide used in the manufacture of regenerated cellulose can be purified by passage through a strongly basic anion-exchange resin. The resin is regenerated by treatment with (1) an aqueous solution of a strong inorganic acid such as hydrochloric or sulphuric acid and (2) an aqueous solution of sodium hydroxide.

Synthesis and Structures of 6-Aryl-1,5-dimethoxycarbonyl-2-methyl-4-morpholino-1,3-cyclohexadienes and Related Compounds

Abstract: Reaction of benzaldehyde (1a) with methyl acetoacetate (2) in the presence of morpholine (or piperidine) and AcOH in refluxing C6H6 yielded a new condensation product, 1, 5-dimethoxycarbonyl-2-methyl-4-morpholino (or piperidino)-6-phenyl-1, 3-cyclohexadiene (3a or 10a), along with a usual product, benzylideneacetoacetate (4a). Under the conditions determined as optimum, 3a was prepared in 86% yield. However, reaction of 1a and 2 in the presence of morpholine (or piperidine) in EtOH solution yielded 4a, a poly-substituted cyclohexanone derivative (5a) and a cyclohexenone derivative (7a), while the production of 3a was not detected. Compound 3a (or 10a) was also prepared by an alternative procedure of condensation of 5a or 6a with morpholine (or piperidine) in the presence of TiCl4. Compound 6a was prepared by dehydration of 5a under acidic conditions. Acid hydrolysis of 3a afforded 6'a, which is the C-4 epimer of 6a. The configurations of 3a, 6a and 6'a were assigned on the basis of the proton nuclear magnetic resonance (1H-NMR) spectra. Mechanisms of the formation of 3a are discussed. Some of 3 and related compounds exhibited potent calcium channel-blocking activity.

Ring‐Transformation von Imidazolidin–2,4‐dionen ( = Hydantoinen) zu 4H‐Imidazolen bei der Umsetzung mit 3‐(Dimethylamino)‐2,2‐dimethyl‐2H ‐azirin

Abstract: Ring Transformation of Imidazolidine-2,4-diones ( = Hydantoins) to 4H-Imidazoles in the Reaction with 3-(Dimethylamino)-2,2-dimethyl-2H-azirines At ca. 70°, 3-(dimethylamino)-2,2-dimethyl-2H -azirine (1) and 5,5-disubstituted hydantoins 4 in MeCN or i-PrOH give 2-(1-aminoalkyl)-5-(dimethylamino)-4,4-dimethyl-4H -imidazoles 5 in good yield (Scheme 2). These products are decarboxylated 1:1 adducts of 1 and 4. A reaction mechanism is suggested in analogy to the previously reported reactions of 1 and NH-acidic heterocycles containing the CONHCONH moiety (Scheme 5). The formation of ureas 6 and 7 can be rationalized by trapping the intermediate isocyanate F by an amine. No reaction is observed between 1 and 1,5,5- or 3,5,5-trisubstituted hydantoins in refluxing MeCN or i-PrOH, but an N-isopropylation of 1,5,5-trimethylhydantoin (8b) occurs in the presence of morpholine (Scheme 3). The reaction of the bis(azirine)dibromozink complex 11 and hydantoines 4 in refluxing MeCN yields zink complexes 12 of the corresponding 2-(1-aminoalkyl)-4H -imidazoles 5 (Scheme 4).

Mechanisms and stereochemistry of amine substitution reactions at the carbon-nitrogen double bond

Abstract: The reaction of (Z)-O-methyl-nitrobenzohydroximoyl chloride [4-NO 2 C 6 H 4 C(CI)=NOCH 3 ] with morpholine, piperidine, pyrrolidine, and azetidine gives the corresponding (Z)-amidoximes (4-NO 2 C 6 H 4 C(NR 1 R 2 )=NOCH 3 ] The rate equations for these reactions in benzene solution contain both first-order and second-order terms in amine

Thermal stability of three amines in pressurized water reactor secondary systems. Laboratory and loop experiments

Abstract: Laboratory and loop tests have been carried out in order to investigate the thermal stability of the three amines, morpholine, AMP (aminomethylpropanol) and sarcosine in PWR secondary conditions. Laboratory experiments have been performed in a titanium autoclave at 300°C. The results pointed out high thermal decomposition rates of AMP and sarcosine. A decomposition mechanism is proposed for the 3 amines. Loop tests have been performed in order to compare steam cycle conditioning with ammonia, morpholine and AMP. The amine concentrations and the decomposition products such as acetate and formate have been followed around the secondary circuit of the ORION loop which reproduces the main physico-chemical characteristics of a PWR secondary circuit. These concentrations are reported together with the evolution of cationic conductivities. The influence of oxygen concentration on amine thermal stability has been observed. Results are expressed also in terms of decomposition rates and of relative volatility.

Enzymatic preparation of optically active fungicide intermediates in aqueous and in organic media

Abstract: Pure stereoisomers of two new triazole and morpholine fungicides were prepared starting from enzymatically synthesized chiral alcohols intermediates. Two resolution strategies were compared: lipase-catalyzed hydrolysis of corresponding acetates in water and lipase-catalyzed transesterification of alcohols in organic solvent. The antifungal activity of optically pure enantiomers of the synthesized fungicides were investigated In vftro and in vfvo against a variety of fungi, showing an activity ratio (R-form / S-form) UP to 400.

Palladium-catalysed direct amination of 2,3-dihydrofuran by morpholine

Abstract: The first palladium-catalysed condensation of an amine with an alkene has been observed on 2,3-dihydrofuran and morpholine with 45 turnovers.

Thiophene and pyridine antipsychotic agents

Abstract: Compounds of the general formula I ##STR1## wherein A is N; Ar is aryl, substituted aryl or benzofuranyl, wherein the substituents are selected from C 1 -C 8 alkoxy; B is CO or CH 2 and HET is selected from any of piperizine, piperidine, hexahydroazepine, morpholine, thiomorpholine or pyrrolidine, which may be substituted with one of more oxo groups are disclosed as novel antipsychotic agents. Pharmaceutical compositions and methods of treating convulsions employing such compounds of formula I are also disclosed.

Highly sterically hindered carbon acids: the intrinsic reactivity of 5,5′,5″-trimethyl- and 3,3′,3″,5,5′,5″-hexamethyl-2,2′,2″,4,4′,4″-hexanitrotriphenylmethanes

Abstract: Rate constants (kpB,k–pBH) for the reversible deprotonation of 5,5′,5″-trimethyl- and 3,3′,3″,5,5′,5″-hexamethyl-2,2′,2″,4,4′,4″-hexanitrotriphenylmethanes (2 and 3) by primary aliphatic amines, piperidine and morpholine as well as by phenoxide anions and hydroxide anion have been measured in H2O–Me2SO (20 : 80) at 25 °C. Comparison of the results obtained with those for 2,2′,2″,4,4′,4″-hexanitrotriphenylmethane (1a) shows that the introduction of methyl groups in positions adjacent to the nitro groups decreases markedly the thermodynamic acidity of the exocyclic CH group: ΔpKa1a2= 1.68; ΔpKa1a3= 6.48. It is suggested that these decreases are very likely the reflection of a twisting of the nitro groups out of their attached aromatic planes and therefore of a reduced resonance stabilization of the conjugated carbanions C-2 and C-3. Other important steric effects are operating in the ionization of 2 and 3. These arise from the accumulation of ortho-nitro groups in the triphenylmethane system which makes the approach of the base reagents from the exocyclic carbon of 2 and 3 very difficult. The finding of extremely low intrinsic reactivities for 2 and 3 and the observation of a much greater catalytic efficiency of primary amines than of secondary amines in assisting the proton transfers are the two most striking manifestations of these F-strain effects.

Formation of nitrosamines in alkaline conditions: a kinetic study of the nitrosation of linear and cyclic secondary amines by nitroalkanes

Abstract: A study has been made of the nitrosation of sixteen secondary amines, six alkylamines (dimethylamine, diethylamine, dipropylamine, diisopropylamine, dibutylamine, diisobutylamine) and ten cyclic secondary amines (2-methylaziridine, azetidine, pyrrolidine, piperidine, 2-methylpiperidine, homopiperidine, heptamethyleneimine, piperazine, 1-methylpiperazine and morpholine) by nitropropane and nitrobutane in a strongly basic medium ([OH–]= 0.1 mol dm–3). The nitrites were not formed in situ(i.e. in the actual bulk of the reaction medium) but rather were isolated, purified and used in pure form. The rate equation (i) was found. v=k2obs[amine][nitrite](i)The fitting of the experimental results to the Taft correlation points to a nucleophilic attack on nitrite esters by the amines. Analysis of the log k2/pKa and log k2/Ei(v) correlations indicates orbital control of the reactions studied. These results, together with the fact that the reactivity of the different amines diminishes ostensibly when the values of the 13C–H nuclear spin coupling constant in the series of corresponding cycloalkanes increase, show that the overall hybridization of the nitrogen atom in the cycle changes from sp2 in the triangular nucleophile methylaziridine to sp3 in larger cycles.The results obtained at different temperatures and with water–tetrahydrofuran media, together with a study of isotope effects suggest that these reactions occur through a highly ordered transition state and that the role of solvation should not be overlooked.

Synergistic combinations of 2-methyl-3-isothiazolone and certain commercial biocides

Abstract: Synergistic microbicidal compositions are disclosed, comprising 2-methyl-3-isothiazolone and one or more of sodium dichlorophene, bis-(2-hydroxy-5-chlorophenyl) sulfide, benzylbromoacetate, dodecylamine, 4-(2-nitrobutyl) morpholine and dipropylamine ether for more effective, and broader control of microorganisms in various systems.

Thermally reversible thickening agent

Abstract: PURPOSE:To provide a thermally reversible thickening agent having easily and continuously adjustable transition temperature, composed of a water-soluble vinyl polymer having reversible temperature-viscosity relationship and useful for the improvement of the temperature-viscosity relationship of various aqueous liquids, the gelatinization of the liquids at high temperature, etc. CONSTITUTION:The thickening agent is composed of a water-soluble vinyl polymer (having a molecular weight of preferably 10,000-2,000,000) containing >=50wt.% of a vinylcarboxylic acid ester of an alkylene oxide adduct of an active hydrogen compound having nitrogen-containing ring (preferably morpholine, 2-methylmorpholine, etc., having morpholine ring) as a constituent unit. The water-soluble vinyl polymer is preferably (meth)acrylic acid ester of a 1-20mol ethylene oxide and/or propylene oxide adduct of a (substituted) morpholine. The polymer has reversible temperature-viscosity relationship and increases the viscosity of an aqueous liquid above a specific transition temperature.

High Yield Room Temperature Synthesis And Spectral Studies Of Tri(Amino)Silanes: (R2n)3SIH

Abstract: Tri(amino)silanes were prepared by the condensation of trichlorosilane with secondary amines in 1:6 molar ratio. Reactions of trichlorosilane with pyrrolidine, piperidine, hexamethyleneimine, morpholine, N-methylpiperazine and diethylamine afford the tri(amino)silanes in nearly quantitative yields. Their physical and spectroscopic properties are discussed. All these compounds are highly sensitive to moisture and hydrolyse to silica and the respective amine with the evolution of hydrogen. The compounds have been characterised by IR, 1H NMR, [1H]29Si NMR spectroscopic methods and CHN elemental analysis.

Paper sizing using copolymers of long-chain olefins and maleic anhydride in the form of the semiamides with morpholine

Abstract: of the Disclosure: Copolymers of (a) C12 - to C24 -monoolefins and (b) maleic anhydride or itaconic anhydride, having molecular weights of from 800 to 100,000 g/mol, in the form of partially or completely neutralized semiamides with morpholine, in aqueous solution or dispersion, can be used as sizes for paper.

5-isoquinolinesulfonic acid amide derivative

Abstract: PURPOSE:To provide a new compound inhibiting a protein phosphorylation enzyme and exhibiting various pharcologic actions. CONSTITUTION:The compound of formula I (R is NHCH2CH2R , group of formula II, formula III, etc.; R is morpholin-1-yl, 2-chlorobenzylamino, etc.), e.g. 5-(2-morpholinoethylaminosulfonyl)isoquinoline. The compound of formula I can be produced by reacting a compound of formula IV with a compound of the formula R NH2 (R is group of formula V, etc.) in a solvent (e.g. dichloromethane) in the presence of an acid acceptor (e.g. triethylamine) at -30 to +100 deg.C. (2-Aminoethyl)morpholine is an example of the compound of the formula R NH2 and the amount of the compound is 1-5 equivalent based on the compound of formula IV.

Radical polymerization of isopropyl tert‐butyl fumarate and maleate, and characterization of the resulting polymers

Abstract: It was found that radical polymerization of isopropyl tert-butyl fumarate (iPtBF) with AIBN as initiator gave high molecular weight polymers in high yield. It was confirmed that iPtBF produced by in situ monomer isomerization of isopropyl tert-butyl maleate (iPTBM) homopolymerized to give a polymer. radical copolymerization of iPtBM with styrene in the presence or absence of morpholine as isomerization catatlyst was also performed and monomer reactivity ratios obtained and compared. It was revealed that the isomerization rate of iPtBM showed first-order dependence on the concentration of iPtBM and morpholine

Chemoenzymic synthesis and fungicidal activity of the four pure stereoisomers of a new morpholine derivative

Abstract: Four optically pure stereoisomers of 2,6-dimethyl-4-[2-methyl-3-[3-(cyclopropylmethoxy)phenyl]propyl]-morpholine (1), a new broad-spectrum morpholine fungicide, were prepared starting from the chiral precursor 2-methyl-3-[3-(benzyloxy)phenyl]-1-propanol (2). Optically active 2 was obtained by lipase-catalyzed kinetic resolution of (R, S)-2 and by stereoselective bakers' yeast reduction of 2-methyl-3-[3-(benzoyloxy)phenyl]propenal (4). The biological activity of the pure stereoisomers has been evaluated in vitro against a variety of fungi and in vivo against Erysiphe graminis on wheat and Helminthosporium teres on barley

Base Catalyzed Condensation of Thiobarbituric Acid with Some Aromatic Aldehydes

Abstract: In this paper the base catalyzed condensation reaction of 2-thiobarbituric acid with some aromatic aldehydes resulting in the formation of 5-arylidene-2-thiobarbituric acids is described. The condensation reaction of 2-thiobarbituric acid was carried out with 4-methoxybenzaldehyde, 4-ethoxybenzaldehyde, 4-benzyloxybenzaldehyde, and 1-naphthaldehyde using morpholine as a catalyst.