Synthesis Of Morpholines Research Articles

Synthesis of Morpholine-, Piperidine-, and N-Substituted Piperazine-Coupled 2-(Benzimidazol-2-yl)-3-arylquinoxalines as Novel Potent Antitumor Agents.

A novel series of 2-(benzimidazol-2-yl)quinoxalines with three types of pharmacophore groups, namely, piperazine, piperidine, and morpholine moieties, which are part of known antitumor drugs, was designed and synthesized. The compounds have been characterized by NMR and IR spectroscopy, high- and low-resolution mass spectrometry, and X-ray crystallography. 2-(Benzimidazol-2-yl)quinoxalines with N-methylpiperazine substituents showed promising activity against a wide range of cancer lines, without causing hemolysis and showing little cytotoxicity against normal human Wi-38 cells (human fetal lung). A mixture of regioisomers 2-(benzimidazol-2-yl)-3-(4-fluorophenyl)-6(and 7)-(4-methylpiperazin-1-yl)quinoxalines (mri BIQ 13da/14da) showed a highly selective cytotoxic effect against human lung adenocarcinoma (cell line A549) with a half-maximal inhibitory concentration at the level of doxorubicin with a selectivity index of 12. The data obtained by flow cytometry, fluorescence microscopy, and multiparametric fluorescence analysis suggested that the mechanism of the cytotoxic effect of the mri BIQ 13da/14da on A549 cells may be associated with the stopping of the cell cycle in phase S and inhibition of DNA synthesis as well as with the induction of mithochondrial apoptosis. Thus, mri BIQ 13da/14da can be considered as a leading compound deserving further study, optimization, and development as a new anticancer agent.

Lewis Acid-Catalyzed Halonium Generation for Morpholine Synthesis and Claisen Rearrangement.

We disclose here practical strategies toward the synthesis of morpholines and Claisen rearrangement products based on the divergent reactivity of a common halonium intermediate. These reactions employ widely available alkenes in a Lewis acid-catalyzed halo-etherification process that can then transform them into the desired products with exceptional regioselectivity for both activated and unactivated olefins. Our mechanistic probe reveals an interesting regiochemical kinetic resolution process.

Morpholine As a Scaffold in Medicinal Chemistry: An Update on Synthetic Strategies.

Morpholine is a frequently used heterocycle in medicinal chemistry and a privileged structural component of bioactive molecules. This is mainly due to its contribution to a plethora of biological activities as well as to an improved pharmacokinetic profile of such bioactive molecules. The synthesis of morpholines is a subject of much study due to their biological and pharmacological importance, with the last such review being published in 2013. Here, an overview of the main approaches toward morpholine synthesis or functionalization is presented, emphasizing on novel work which has not been reviewed so far. This review is an update on synthetic strategies leading to easily accessible libraries of bioactives which are of interest for drug discovery projects.

Recent progress in the synthesis of morpholines

The morpholine (1,4-oxazinane) motif attracted significant attention due to its widespread availability in natural products and biologically relevant compounds. This review describes recent advances in the synthesis of morpholines and their carbonyl-containing analogs from 1,2-amino alcohols, aziridines, epoxides, and related compounds. Special attention is paid to the syntheses performed in a stereoselective manner and using transition metal catalysis. Selected works published since 2013 are covered.

Stereoselective Polymer-Supported Synthesis of Morpholines

Stereoselective Polymer-Supported Synthesis of Morpholines

Synthesis of Morpholines and Piperazines by an Ugi Multicomponent Reaction

Key words morpholines - piperazines - Ugi reaction - multicomponent reaction

Nitro Epoxide Based Synthesis of Morpholines and Benzoxazines

Nitro Epoxide Based Synthesis of Morpholines and Benzoxazines

ChemInform Abstract: General and Cost‐Effective Synthesis of 1‐Heteroaryl/Arylcycloalkylamines and Their Broad Applications.

AbstractThe new method to synthesize 1‐(hetero)arylsubstituted cycloalkylamines from readily available heteroarylacetate is reported.

General and cost-effective synthesis of 1-heteroaryl/arylcycloalkylamines and their broad applications

A general and cost-effective route has been developed to synthesize 1-heteroarylsubstituted cycloalkylamines from readily available heteroarylacetate in good yields. This synthesis features a LHMDS promoted cyclization and one-pot hydrolysis/Curtius rearrangement. This route can be easily carried out on multi-gram scale and be also used to prepare 1-arylsubstituted cycloalkyl/cycloheteroalkylamines. 1-Heteroaryl/arylsubstituted cycloalkyl/cycloheteroalkylamines are versatile building blocks and their applications in organic and medicinal chemistry have been demonstrated in the synthesis of morpholine and N-methylpiperazine analogues and a known Rho kinase inhibitor compound 9.

ChemInform Abstract: Synthesis of Morpholine or Piperazine Derivatives Through Gold‐Catalyzed Cyclization Reactions of Alkynylamines or Alkynylalcohols.

A convenient and efficient synthetic method for the construction of morpholine and piperazine derivatives in moderate to good yields was established. The reaction proceeds smoothly with 1.0 mol% gold catalyst loading. A plausible mechanism involving the cascade cyclization and isomerizations to produce the six-membered ring was proposed and supported by deuterium labeling experiments.

Synthesis of morpholine or piperazine derivatives through gold-catalyzed cyclization reactions of alkynylamines or alkynylalcohols

A gold catalyzed reaction for the preparation of morpholine and piperazine derivatives from alkynylalcohols or alkynylamines was developed.

ChemInform Abstract: An Asymmetric Ugi Three‐Component Reaction Induced by Chiral Cyclic Imines: Synthesis of Morpholine— or Piperazine—Ketocarboxamide Derivatives.

AbstractTreatment of chiral cyclic imines like (I) and (VII) with acids and isocyanides allows an efficient and stereoselective access to novel morpholines.

A Modular Approach to the Synthesis of Morpholines

A Modular Approach to the Synthesis of Morpholines

Synthesis of Enantiopure 2‐Aryl(Alkyl)‐2‐trifluoromethyl‐Substituted Morpholines and Oxazepanes

AbstractThe synthesis of morpholines and oxazepanes derivatives containing a trifluoromethyl group on a quaternary carbon has been achieved from a common enantiopure O‐allyl amino ether precursor. Classic 6‐exo iodoamination provided the iodomorpholines, versatile synthetic intermediates, whereas a hydrozirconation/iodination sequence allowed the synthesis of oxazepanes by a 7‐endo cyclisation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Role of the support of the nickel catalyst in the synthesis of morpholine from diethylene glycol and ammonia

The strong effect of the support on the physical properties and catalytic activity and selectivity of high-loaded nickel catalysts (about 55 wt.% Ni) used in reductive amination of diethylene glycol (DEG) and diethylene glycol amine (DEGA) to form morpholine was confirmed. In DEG amination, catalytic activity was proportional to the dispersion of metallic nickel only, while in DEGA amination catalytic activity depended on the acidity of the catalysts.

ChemInform Abstract: Synthesis of Morpholines. Part 3. Application of an Oxymercuration‐ Demercuration Reaction to the Synthesis of 2‐Methylmorpholines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Morpholines-(III): Some Further Aspects of the Cyclodehydrohalogenation of ω -[N-(aryl)-N-(halogenoacyl)]-aminoacetophenones

The formation of a 2-oxo-azetidine from N-phenyl-N-chloroacetyl-4-fluoro-phenacylamine, and 3-oxo-morpholines from corresponding 4-bromo-derivatives 2 indicates the possibility of the existence of dπ-acceptor resonance between the aromatic ring and the bromo-substituent. H-NMR studies of some morpholines reported earlier 3 indicate a planar heterocyclic structure with a rapidly inverting N₋aryl substituent. Where the rotation of the N-aryl group is strongly hindered 16, the C2 methylene protons show a geminai coupling of -14.5 Hz4. The 2-oxo-azetidine (4) shows an ABX coupling pattern for its ring protons. Preliminary work attempting to extend the synthesis of morpholines to azepines has resulted instead in the formation of a pyrrolidone.

A New Synthesis of Morpholine

A New Synthesis of Morpholine