23328-69-0

Basic information

• Product Name: 4-chloromorpholine
• Synonyms: 4-chloromorpholine;N-Chloromorpholine;Einecs 245-588-1;Morpholine, 4-chloro-
• CAS NO: 23328-69-0
• Molecular Formula: C₄H₈ClNO
• Molecular Weight: 121.56542
• EINECS: 245-588-1
• Mol File: 23328-69-0.mol

Chemical Properties

• Boiling Point: 161.2 °C at 760 mmHg
• Flash Point: 51.3 °C
• Appearance: /
• Density: 1.21 g/cm³
• Vapor Pressure: 2.3mmHg at 25°C
• Refractive Index: 1.488
• CAS DataBase Reference: 4-chloromorpholine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-chloromorpholine(23328-69-0)
• EPA Substance Registry System: 4-chloromorpholine(23328-69-0)

Safety Data

• Hazardous Substances Data: 23328-69-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-chloromorpholine is used as a building block for the synthesis of various pharmaceuticals, contributing to the development of new drugs and improving the efficacy of existing ones.
Used in Agrochemical Industry:
4-chloromorpholine is used as a building block for the synthesis of agrochemicals, aiding in the creation of effective pesticides and other agricultural products.
Used as a Catalyst or Reagent in Chemical Reactions:
4-chloromorpholine is utilized as a catalyst or reagent in various chemical reactions, facilitating specific transformations and improving the overall efficiency of the processes.

InChI:InChI=1/C4H8ClNO/c5-6-1-3-7-4-2-6/h1-4H2

Upstream product

• 110-91-8 morpholine 
• 5625-90-1 4-(morpholinomethyl)morpholine 
• 777851-20-4 N-chloro-p-nitrobenzenesulfonamide 
• 10024-89-2 morpholin hydrochloride 
• 7681-52-9 sodium hypochlorite 
• 4856-95-5 morpholine-borane 
• 80584-36-7 morpholine-borane-d3 

Downstream Products

• 102-77-2 4-(benzothiazole-2-sulfenyl)-morpholine 
• 24171-17-3 N-(N,N-dimethylthiocarbamoyldithioyl)morpholine 
• 1530-89-8 N-cyanomorpholine 
• 4837-31-4 4-Phenylsulfanyl-morpholine 
• 2244-48-6 N-morpholinyl-2-pyridinesulfenamide 
• 6339-26-0 4-tosylmorpholine 
• 649-15-0 N,N-diethyl-4-methylbenzenesulfonamide 
• 98-59-9 p-toluenesulfonyl chloride 
• 78488-61-6 N-(phenyldichloroseleno)morpholine 
• 127878-11-9 4-Benzylselanyl-morpholine 
• 7257-55-8 4-morpholinyl benzyl sulfide 
• 98525-54-3 trans-2-chlorocyclohexyl 4-morpholinesulfonate 
• 2158-02-3 morpholine-4-carboxylic acid amide 
• 92-53-5 4-Phenylmorpholine 

Relevant articles and documents

Haloamines as Bifunctional Reagents for Oxidative Aminohalogenation of Maleimides

An unprecedented copper-catalyzed oxidative aminohalogenation of electron-deficient maleimides with secondary amines and NXS (X = Cl, Br, I) was developed, in which the N-X bonds generated in situ were used as difunctionalized reagents. The distinctive features of this multicomponent reaction include a simple green catalytic system, a spectral substrate range, and the late-stage modification of drug molecules. Most importantly, this umpolung radical cascade strategy exploits the in situ formation of N-iodoamines that enable efficient alkene aminoiodination.

Two-step continuous flow synthesis of amide via oxidative amidation of methylarene

A green and efficient method for the synthesis of amides has been developed through oxidative amidation between methylarenes with amines in a two-step continuous flow system. This method integrates methylarene oxidation and amide formation into a single operation which is usually accomplished separately. Oxidation with tert-butyl hydroperoxide (TBHP) as “green” oxidant, the synthesis of amides under mild reaction conditions in continuous flow system and the utilization of methylarenes as starting material make this methodology novel and environment friendly. The practical value of this method is highlighted through the synthesis of high-profile pharmaceutical agents, acetylprocainamide.

Synthesis of aromatic sulfonamides through a copper-catalyzed coupling of aryldiazonium tetrafluoroborates, DABCO·(SO2)2, and N-Chloroamines

A copper-catalyzed aminosulfonylation of aryldiazonium tetrafluoroborates, DABCO·(SO2)2, and N-chloroamines is described. This coupling reaction provides an efficient and simple approach to a wide range of sulfonamides in moderate to good yields under mild conditions. Mechanistic investigation suggests that a radical process and transition-metal catalysis are merged in this tandem reaction.

A green, isocyanide-based three-component reaction approach for the synthesis of multisubstituted ureas and thioureas

A one-pot, isocyanide based multicomponent protocol was presented starting from secondary amines towards (thio)urea derivatives and utilized for the construction of a diverse 27-membered chemical library. Following a green compatible microwave assisted condition, the formed N,N′-multisubstituted (thio)ureas were obtained in up to 85% yield.

Aryne Trifunctionalization Enabled by 3-Silylaryne as a 1,2-Benzdiyne Equivalent

An unprecedented aryne 1,2,3-trifunctionalization protocol from 2,6-bis(silyl)aryl triflates was developed under transition-metal-free conditions. The reaction of generated 3-silylaryne with both pyridine N-oxide and N-hydroxylamide afforded o-silyl triflate/tosylate in a one-pot transformation, allowing the formation of 2,3-aryne precursors with various vicinal pyridinyl/amido substituents. These pyridinyl-substituted 2,3-aryne intermediates exhibit a broad scope of reactivity with diverse arynophiles in good yields and high selectivity.

Copper-catalyzed one-pot oxidative amidation between methylarenes and amines

A new method for the direct one-pot oxidative amidation between methylarenes and amines catalyzed by copper has been developed. This method integrates methylarene oxidation and amide bond formation, which are usually accomplished separately, into a single operation. In addition, the reaction provides a relatively high yield and has a wide substrate scope. Moreover, the starting reagents are abundant and available in a convenient way at a cheaper price.

Copper-catalyzed one-pot oxidative amidation of alcohol to amide via C-H activation

A one-pot oxidative amidation of both aliphatic and aromatic alcohols with N-chloramines, prepared in situ from many types of primary and secondary amines, was developed. This cross-coupling reaction integrates alcohol oxidation and amide bond formation, which are usually accomplished separately, into a single operation. And it was green, simple and convenient, which has a wide substrate scope and makes use of cheap, abundant, and easily available reagents. The practical value of this method is highlighted through the synthesis of a high-profile pharmaceutical agent, acetylprocainamide.

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

The continuous flow synthesis of a range of organic solutions of N,N-dialkyl-N-chloramines is described using either a bespoke meso-scale tubular reactor with static mixers or a continuous stirred tank reactor. Both reactors promote the efficient mixing of a biphasic solution of N,N-dialkylamine in organic solvent, and aqueous sodium hypochlorite to achieve near quantitative conversions, in 72-100% in situ yields, and useful productivities of around 0.05 mol/h with residence times from 3 to 20 minutes. Initial calorimetric studies have been carried out to inform on reaction exotherms, rates and safe operation. Amines which partition mainly in the organic phase require longer reaction times, provided by the CSTR, to compensate for low mass transfer rates in the biphasic system. The green metrics of the reaction have been assessed and compared to existing procedures and have shown the continuous process is improved over previous procedures. The organic solutions of N,N-dialkyl-N-chloramines produced continuously will enable their use in tandem flow reactions with a range of nucleophilic substrates.

Synthesis of ortho -haloaminoarenes by aryne insertion of nitrogen-halide Bonds

A rapid and general access to ortho-haloaminoarenes has been developed by aryne insertion into N-chloramine, N-bromoamine, and N-iodoamine bonds via two complementary protocols harnessing fluoride-promoted 1,2-elimination of ortho-trimethylsilyl aryltriflates. Typically, electron-deficient N-chloramines effectively react with aryne intermediates generated at elevated temperature with CsF, while less stable N-haloamines are found more efficient under milder, TBAF-mediated aryne formation at room temperature. Both protocols demonstrate a good level of regioselectivity and functional group tolerance. Efforts to elucidate the mechanism of N-X insertion are also discussed. The practical value of this transformation is highlighted by rapid synthesis of novel analogues of the antipsychotic cariprazine.

Transition-metal free umpolung carbon-nitrogen versus carbon-chlorine bond formation

The formation of carbon-nitrogen (C-N) bonds via an umpolung substitution reaction has been achieved at -78 °C without the need for catalysts, ligands, or additives. The scope is limited to aryl Grignard reagents with N-chloroamines. The findings in this manuscript serve as a reference point for all C-N bond formations involving N-chloroamines and organometallic reagents. Knowing the yields of uncatalyzed reactions will be useful when determining the success of future catalytic methods.