PRODUCTS

MORPHOLINE

CAS Number: 110-91-8
IUPAC name: Morpholine
Chemical formula: C4H9NO
EC Number: 203-815-1

Morpholine is an organic chemical compound having the chemical formula O(CH2CH2)2NH.
This heterocycle features both amine and ether functional groups.
Because of the amine, morpholine is a base; its conjugate acid is called morpholinium.
For example, treating morpholine with hydrochloric acid makes the salt morpholinium chloride.
Morpholine is a colorless liquid with a weak, ammonia- or fish-like odor.
The naming of morpholine is attributed to Ludwig Knorr, who incorrectly believed it to be part of the structure of morphine.

Morpholine is often produced industrially by the dehydration of diethanolamine with sulfuric acid.

Industrial applications
Morpholine is a common additive, in parts per million concentrations, for pH adjustment in both fossil fuel and nuclear power plant steam systems.
Morpholine is used because its volatility is about the same as water, so once it is added to the water, its concentration becomes distributed rather evenly in both the water and steam phases.

Morpholine's pH-adjusting qualities then become distributed throughout the steam plant to provide corrosion protection.
Morpholine is often used in conjunction with low concentrations of hydrazine or ammonia to provide a comprehensive all-volatile treatment chemistry for corrosion protection for the steam systems of such plants.
Morpholine decomposes reasonably slowly in the absence of oxygen at the high temperatures and pressures in these steam systems.

Organic synthesis of Morpholine:
Morpholine undergoes most chemical reactions typical for other secondary amines, though the presence of the ether oxygen withdraws electron density from the nitrogen, rendering it less nucleophilic (and less basic) than structurally similar secondary amines such as piperidine. For this reason, it forms a stable chloramine.

Morpholine is commonly used to generate enamines.

Morpholine is widely used in organic synthesis.
For example, it is a building block in the preparation of the antibiotic linezolid, the anticancer agent gefitinib (Iressa) and the analgesic dextromoramide.

In research and in industry, the low cost and polarity of morpholine lead to its common use as a solvent for chemical reactions.

Agriculture
As a fruit coating
Morpholine is used as a chemical emulsifier in the process of waxing fruit.
Naturally, fruits make waxes to protect against insects and fungal contamination, but this can be lost as the fruit is cleaned.
A small amount of new wax is applied to replace it.
Morpholine is used as an emulsifier and solubility aid for shellac, which is used as a wax for fruit coating.
The European Union has forbidden the use of morpholine in fruit coating.

Consumer Uses
Morpholine is used in the following products: adhesives and sealants, coating products, inks and toners, anti-freeze products, biocides (e.g. disinfectants, pest control products), fuels, photo-chemicals, polishes and waxes, washing & cleaning products and paper chemicals and dyes.
Other release to the environment of Morpholine is likely to occur from: indoor use (e.g. machine wash liquids/detergents, automotive care products, paints and coating or adhesives, fragrances and air fresheners) and outdoor use.

Article service life
Other release to the environment of Morpholine is likely to occur from: outdoor use in long-life materials with low release rate (e.g. metal, wooden and plastic construction and building materials), outdoor use in long-life materials with high release rate (e.g. tyres, treated wooden products, treated textile and fabric, brake pads in trucks or cars, sanding of buildings (bridges, facades) or vehicles (ships)), indoor use in long-life materials with low release rate (e.g. flooring, furniture, toys, construction materials, curtains, foot-wear, leather products, paper and cardboard products, electronic equipment) and indoor use in long-life materials with high release rate (e.g. release from fabrics, textiles during washing, removal of indoor paints).

Morpholine can be found in complex articles, with no release intended: Vehicles (e.g. personal vehicles, delivery vans, boats, trains, metro or planes)), machinery, mechanical appliances and electrical/electronic products e.g. refrigerators, washing machines, vacuum cleaners, computers, telephones, drills, saws, smoke detectors, thermostats, radiators, large-scale stationary industrial tools), vehicles and machinery, mechanical appliances and electrical/electronic products (e.g. computers, cameras, lamps, refrigerators, washing machines). Morpholine can be found in products with material based on: metal (e.g. cutlery, pots, toys, jewellery), metal used for large surface area articles (e.g. construction and building materials used for roof sheets, pipes), metal used for packaging (excluding food packaging), metal used for furniture & furnishings (e.g. outdoor furniture, benches, tables), wood used for large surface area articles (e.g. construction and building materials for floors, claddings), wood used for furniture & furnishings and wood.

Widespread uses by professional workers
Morpholine is used in the following products: washing & cleaning products.
Morpholine is used in the following areas: building & construction work.
Morpholine is used for the manufacture of: chemicals and fabricated metal products.
Other release to the environment of Morpholine is likely to occur from: indoor use (e.g. machine wash liquids/detergents, automotive care products, paints and coating or adhesives, fragrances and air fresheners) and outdoor use.

Formulation or re-packing
Morpholine is used in the following products: adhesives and sealants, coating products, fillers, putties, plasters, modelling clay, finger paints, metal surface treatment products, non-metal-surface treatment products and inks and toners.

Release to the environment of Morpholine can occur from industrial use: formulation of mixtures, formulation in materials, in processing aids at industrial sites, in the production of articles, as processing aid and of substances in closed systems with minimal release.

Uses at industrial sites
Morpholine is used in the following products: washing & cleaning products, pH regulators and water treatment products and polymers.
Morpholine has an industrial use resulting in manufacture of another substance (use of intermediates).
Morpholine is used in the following areas: building & construction work.

Morpholine is used for the manufacture of: chemicals and fabricated metal products.
Release to the environment of Morpholine can occur from industrial use: in processing aids at industrial sites, in the production of articles, of substances in closed systems with minimal release and as an intermediate step in further manufacturing of another substance (use of intermediates).

Morpholine is an organic heteromonocyclic compound whose six-membered ring contains four carbon atoms and one nitrogen atom and one oxygen atom that lies opposite to each other; the parent compound of the morpholine family.
Morpholine is a saturated organic heteromonocyclic parent and a member of morpholines.
Morpholine is a conjugate base of a morpholinium.

Morpholine appears as a colorless liquid with a fishlike odor.
Corrosive to tissue. Less dense than water and soluble in water.
Vapors heavier than air. Used to make other chemicals, as a corrosion inhibitor, and in detergents.

Molecular Weight: 87.12
XLogP3: -0.9|
Hydrogen Bond Donor Count: 1
Hydrogen Bond Acceptor Count: 2

Rotatable Bond Count: 0
Exact Mass: 87.068413911
Monoisotopic Mass: 87.068413911
Topological Polar Surface Area: 21.3 Å²

Heavy Atom Count: 6
Complexity: 34.5
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0

Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1

Appearance: Colorless liquid
Odor: Weak ammonia-like or fish-like
Density: 1.007 g/cm3
Melting point: −5 °C
Boiling point: 129 °C

Morpholine is a colorless organic compound with the chemical formula O(CH2CH2)2NH, which has heterocycle features of both amine and ether functional groups.
Morpholine and its derivatives have been used as rubber additives, corrosion inhibitors, solvents, optical brighteners, antioxidants, and in manufacturing a range of drugs and herbicides.
Morpholine is a versatile intermediate with a weak, ammonia- or fish-like odor and various applications.

Morpholine is used as an essential building block mainly in rubber, water treatment, optical brighteners, pharma, agro-industry, and solvent for the fiber industry.
Morpholine is a highly versatile chemical used extensively as a corrosion inhibitor in steam boiler systems and as an intermediate in manufacturing products used as optical brighteners, textile lubricants, softening agents, adjuvants, antioxidants, plasticizers, and viscosity improvers.

Morpholine and derivatives may be used as an accelerator/catalyst in epoxy formulations or as catalyst/initiator in UV-curable acrylic-based systems for coatings and adhesives.
Morpholine is a Solvent with good solubility power, high polarity, and low molecular weight.

Morpholine is used in steam-generating-boiler systems plants to prevent internal corrosion of condensate return lines.

Replacement costs for underground steam/condensate systems are high.
A high cost is associated with reduced efficiency while systems are corroding.
Neutralizing amine morpholine plays a significant role in the curtailment of condensate corrosion.
Morpholine is a neutralizing amine to give the most economical and effective results in different systems.

Neutralizing Amine Chemistry
Several different neutralizing amine components are typically used in the treatment of boiler feedwater and/or condensate.
Neutralizing amines have different chemical properties, and it is essential to understand the differences to apply the correct components.
Neutralizing amines typically applied in power plant systems are cyclohexylamine (CHA), methoxypropylamine (MPA), monoethanolamine (ETA), and morpholine.

Neutralizing amines are weak bases that are typically classified in terms of their "neutralizing capacity," "basicity," and "distribution ratio."
The neutralizing capacity measures how much amine it takes to neutralize a given acid.

Usually, it is expressed as the ppm of CO2 (or carbonic acid) neutralized per ppm of neutralizing amine.
Once the acid has been neutralized, each amine has a different ability to boost pH, which is accomplished by the hydrolysis of the amine to form hydroxyl (OH-) ions.

The distribution ratio refers to the volatility of the amine, which is one factor that helps determine how each amine component will partition between the liquid and steam phases. The distribution ratio of a particular amine also influences how much amine is recycled throughout the system, and how many amines will be lost from the system via boiler blowdown and steam venting.

While neutralizing amine chemistry may appear relatively straightforward, it is pretty complex. For example, the distribution ratio for a given amine is a function of pressure, temperature, and pH. This means if you feed more or less neutralizing amine in a given system and affect the pH, the distribution of the amine between the liquid and steam phases will change as well.

In addition, neutralization chemistry is based on the equilibrium chemistry of weak acids and weak bases.
Multiple neutralizing amine and acid components are present in many cases, so it becomes even more challenging to predict the amine distribution and pH profile across the system without using sophisticated computerized modeling techniques or performing extensive empirical in-plant analyses.

The thermal stability of the neutralizing amine must also be considered when designing a treatment program to control FAC. Most amines degrade to some degree in an aqueous, alkaline, high-temperature environment to form carbon dioxide, organic acids, and ammonia. Morpholine, CHA, ETA, and MPA are the most thermally stable amines routinely employed in high-pressure power plant applications.

Morpholine is a neutralizing amine that prevents carbonic acid corrosion in plant or refinery steam condensate systems.

Morpholine is an organic chemical compound with the formula O(CH2CH2)2NH.
This heterocycle features both amine and ether functional groups. Because of the amine, morpholine is a base; its conjugate acid is called morpholinium.
For example, neutralizing morpholine with hydrochloric acid makes the salt morpholinium chloride.

Applications
Rubber Chemicals
The effective use of morpholine is an intermediate in producing delayed-action rubber accelerators.
Accelerators are added to rubber before fabrication to increase the rate of vulcanization.
Morpholine-based delayed-action accelerators are usually made by reacting morpholine with 2-mercaptobenzothiazole.

Corrosion Inhibitors
Morpholine is widely used as a neutralizing amine in combating carbonic acid corrosion in condensate return lines of steam boiler systems.
Morpholine volatilizes with the steam from the boiler.
Morpholine condenses when the steam does, thereby protecting the lines, which otherwise would be subjected to corrosion by the carbonic acid in the steam condensate. Morpholine vapors protect silver and other metals against corrosion and tarnish by acid fumes, such as sulfur dioxide and hydrogen sulfide.

Morpholine is a component of a corrosion inhibitor system that prevents the decomposition of a chlorinated hydrocarbon in a composition containing the chlorinated hydrocarbon and a large amount of water.
Using low levels of morpholine can avoid the corrosion of metal aerosol containers and valves.

Catalysts
Morpholine has been employed as a catalyst for condensing aldehydes and ketones, which contain active methyl or methylene groups. The condensates may be hydrogenated to polyhydroxy compounds, which can be sulfated to form surface-active agents.
Morpholine has also been used as a gelling agent in preparing alumina catalysts to treat hydrocarbons.
Catalysts of a fine particle size suitable for solid fluidized techniques result from this procedure.

Separating Agents
Morpholine's physical and chemical properties make it useful in various purification procedures.
Marked differences in the solubility of the methyl amines in morpholine have led to a convenient extractive method for separating these volatile amines.
Adding morpholine to styrene-containing hydrocarbon mixtures makes isolating substantially pure styrene by azeotropic distillation possible.
Morpholine is the preferred amine in an oil-amine mixture for scrubbing organic sulfur compounds from fuel gas.
Morpholine is also used in the purification of acetylene and certain olefins.

Optical Brighteners
Morpholine is an essential intermediate in the manufacture of optical brighteners.
Optical brighteners are employed by the soap and detergent industry in compounding detergents.
The diamino stilbene triazine type brightener with morpholine as a substituent on one of the triazine rings is particularly effective on cellulosic.
Having more excellent stability to chlorine bleaches than other brighteners, they are particularly suitable for home laundry detergents.

Emulsion polymerization agent
Small quantities of morpholine are used in the emulsion polymerization of monomers, such as butadiene and isoprene, as well as their copolymerization with styrene, acrylonitrile, and the like.

Polymerization inhibitor

Morpholine has been used as a temperature-sensitive polymerization inhibitor.
Small amounts permit complete impregnation of porous materials with molten vinyl pyrrole-type monomers just above their melting points but still allow complete polymerization at slightly higher temperatures.

Agriculture
As a fruit coating
Morpholine is used as a chemical emulsifier in the process of waxing fruit.
Naturally, fruits make waxes to protect against insects and fungal contamination, but this can be lost as the fruit is cleaned.
A small amount of new wax is applied to replace it. Morpholine is used as an emulsifier and solubility aid for shellac and as a wax for fruit coating.
The European Union has forbidden the use of morpholine in fruit coating.

As a component in fungicides
Morpholine derivatives used as agricultural fungicides in cereals are known as ergosterol biosynthesis inhibitors.

Industrial applications
Morpholine is a common additive, in parts per million concentrations, for pH adjustment in fossil fuel and nuclear power plant steam systems.
Morpholine is used because its volatility is about the same as water. Once it is added to the water, its concentration becomes evenly distributed in both the water and steam phases.
Morpholines pH-adjusting qualities then become distributed throughout the steam plant to provide corrosion protection.

Morpholine is often used in conjunction with low concentrations of hydrazine or ammonia to provide a comprehensive all-volatile treatment chemistry for corrosion protection for the steam systems of such plants.
Morpholine decomposes reasonably slowly without oxygen at these steam systems' high temperatures and pressures.

Organic synthesis
Morpholine undergoes most chemical reactions typical for other secondary amines. However, the presence of the ether oxygen withdraws electron density from the nitrogen, rendering it less nucleophilic (and less basic) than structurally similar secondary amines such as piperidine. For this reason, it forms a stable chloramine.

Morpholine is commonly used to generate enamines.
Morpholine is widely used in organic synthesis.
For example, it is a building block in preparing the antibiotic linezolid, the anticancer agent gefitinib (Iressa), and the analgesic dextromoramide.
In research and industry, morpholine's low cost and polarity lead to its everyday use as a solvent for chemical reactions.

How Morpholine is manufactured:
Three methods of producing morpholine have been described:

Reductive ammoniation of diethylene glycol and hydrogen.
Possible catalysts include copper, nickel, cobalt, chromium, molybdenum, manganese, platinum, palladium, rhodium and ruthenium.
Morpholine is recovered by fractional distillation

Dehydration of diethanolamine with a strong acid such as oleum, concentrated sulfuric acid, or hydrochloric acid.
The acid is neutralized by adding an alkali to give the free base of morpholine.
Morpholine is recovered by extraction using an organic solvent or concentrated aqueous alkali followed by distillation.

Heating bis(chloroethyl)ether and anhydrous ammonia in a closed vessel.
After venting the excess ammonia, the product is filtered from ammonium chloride, and purified morpholine is obtained by distillation.

Morpholine is a heterocycle featured in numerous approved and experimental drugs as well as bioactive molecules.
Morpholine is often employed in the field of medicinal chemistry for its advantageous physicochemical, biological, and metabolic properties, as well as its facile synthetic routes.
The morpholine ring is a versatile and readily accessible synthetic building block, it is easily introduced as an amine reagent or can be built according to a variety of available synthetic methodologies.

This versatile scaffold, appropriately substituted, possesses a wide range of biological activities. There are many examples of molecular targets of morpholine bioactive in which the significant contribution of the morpholine moiety has been demonstrated; it is an integral component of the pharmacophore for certain enzyme active‐site inhibitors whereas it bestows selective affinity for a wide range of receptors.

A large body of in vivo studies has demonstrated morpholine's potential to not only increase potency but also provide compounds with desirable drug‐like properties and improved pharamacokinetics.
In this review we describe the medicinal chemistry/pharmacological activity of morpholine derivatives on various therapeutically related molecular targets, attempting to highlight the importance of the morpholine ring in drug design and development as well as to justify its classification as a privileged structure.

Morpholine is used as a boiler water treatment additive in steam systems of power plants and refineries. Morpholine forms an even wax-like coating as morpholine oleate. Morpholine prevents the decomposition of a chlorinated hydrocarbon in a composition containing the chlorinated hydrocarbon and a large amount of water. Morpholine is often used in conjunction with low concentrations of hydrazine or ammonia to provide a comprehensive all-volatile boiler water treatment chemistry for corrosion protection for the steam systems of such plants. Morpholine decomposes reasonably slowly without oxygen at the high temperatures and pressures in these steam systems.

Because its volatility is the same as water, upon addition to water, its concentration becomes distributed relatively evenly in both the water and steam phases. Morpholines pH-adjusting qualities become more dispersed throughout the steam plant to provide corrosion protection.

Morpholine, an organic compound with both amine and ether groups, is obtained by dehydrating diethanolamine with sulphuric acid. Morpholine can be adapted to many different activities for many important applications. Some of its different adaptations can be seen in the following applications. Morpholine functions as an intermediate in the production of rubber chemicals, even as optical brighteners. Morpholine acts as an effective corrosion inhibitor in steam boiler systems. Morpholines can utilize as pharma chemicals and antioxidants for lubricating oils.
Morpholines can be used as emulsifiers in wax and polishes processing industries.

Morpholine is a very good pH adjuster and very effective for nuclear power plants. One more reason for it to be used is that it rates vaporization, which is quite similar to water; so what happens is when it is added to water, it disperses accordingly in water in both of its liquid and vapor phases. Morpholine can also be used as an ingredient in fungicides and bactericides.

Morpholine can be used as a buffer component in the separation of peptides and pathogenic lipopolysaccharides during on-line chromatographic preconcentration coupled to capillary zone electrophoresis–electrospray mass spectrometry analysis from colony isolates:

Morpholine is a simple heterocyclic compound that has great industrial importance and a wide range of applications.
Morpholine and its derivatives have been used as rubber additives, corrosion inhibitors, solvents, optical brighteners, antioxidants and in the manufacture of a range of drugs and herbicides. Consequently, morpholine can occur in a number of industrials effluents and can be disseminated in the environment.
Morpholine is subject to N-nitrosation by nitrites and this reaction gives the potent mutagen N-nitrosomorpholine.
These inconveniences can be avoided by elimination of morpholine from wastewater and effluents by biological treatments.

Other names:
110-91-8
1-Oxa-4-azacyclohexane
Tetrahydro-1,4-oxazine
Diethylene oximide
Diethylenimide oxide
Diethyleneimide oxide
Diethylene imidoxide
Drewamine
Tetrahydro-2H-1,4-oxazine
Tetrahydro-p-oxazine
p-Isoxazine, tetrahydro-
Tetrahydro-1,4-isoxazine
morpholin
BASF 238
Caswell No. 584
2H-1,4-Oxazine, tetrahydro-
4H-1,4-Oxazine, tetrahydro-
NSC 9376
138048-80-3
MFCD00005972
C4H9NO
Tetrahydro-4H-1-4-oxazine
8B2ZCK305O
CHEBI:34856
NSC-9376
DSSTox_CID_5688
DSSTox_RID_77880
DSSTox_GSID_25688
CAS-110-91-8
CCRIS 2482
HSDB 102
MORPHOLINE,REAG
Tetrahydro-p-isoxazine
MORPHOLINE, PRACT
EINECS 203-815-1
UN2054
BRN 0102549
morphline
UNII-8B2ZCK305O
morpho line
morpholine-
AI3-01231
6LR
4H-1, tetrahydro-
Morpholine on Rasta Resin
WLN: T6M DOTJ
EC 203-815-1
NCIMech_000154
Tetrahydro-1, 4-isoxazine
NCIOpen2_007748
Oprea1_317540
Tetryhydro-2H-1,4-oxazine
Tetrahydro-4H-1,4-Oxazine
BIDD:ER0297
Morpholine, analytical standard
CHEMBL276518
DTXSID2025688
NSC9376
AMY22834
BCP24054
STR00194
ZINC1699948
Tox21_202450
Tox21_303240
STL182843
AKOS000118829
DB13669
NA 2054
UN 2054
NCGC00249227-01
NCGC00256942-01
NCGC00259999-01
61791-40-0
DB-030063
FT-0628993
M0465
EN300-18064
Q410243
J-522715