Morpholine

Morpholine^[1]
numbered skeletal formula of the morpholine molecule	perspective skeletal formula of the morpholine molecule
ball-and-stick model of the morpholine molecule	space-filling model of the morpholine molecule
Names
	Preferred IUPAC name Morpholine
	Other names Diethylenimide oxide; 1,4-Oxazinane; Tetrahydro-1,4-oxazine; Diethylene imidoxide; Diethylene oximide; Tetrahydro-p-oxazine
Identifiers
CAS Number	110-91-8 ;
3D model (JSmol)	Interactive image;
Beilstein Reference	102549
ChEBI	CHEBI:34856 ;
ChEMBL	ChEMBL276518 ;
ChemSpider	13837537 ;
ECHA InfoCard	100.003.469
EC Number	203-815-1;
Gmelin Reference	1803
KEGG	C14452 ;
PubChem CID	8083;
RTECS number	QD6475000;
UNII	8B2ZCK305O ;
UN number	2054
CompTox Dashboard (EPA)	DTXSID2025688;
	InChI InChI=1S/C4H9NO/c1-3-6-4-2-5-1/h5H,1-4H2 Key: YNAVUWVOSKDBBP-UHFFFAOYSA-N ; InChI=1/C4H9NO/c1-3-6-4-2-5-1/h5H,1-4H2 Key: YNAVUWVOSKDBBP-UHFFFAOYAU;
	SMILES C1CNCCO1;
Properties
Chemical formula	C4H9NO
Molar mass	87.122 g·mol−1
Appearance	Colorless liquid
Odor	Weak ammonia-like or fish-like
Density	1.007 g/cm3
Melting point	−5 °C (23 °F; 268 K)
Boiling point	129 °C (264 °F; 402 K)
Solubility in water	miscible
Vapor pressure	6 mmHg (20 °C)
Acidity (pKa)	8.36 (of conjugate acid)
Magnetic susceptibility (χ)	-55.0·10−6 cm3/mol
Hazards
	Occupational safety and health (OHS/OSH):
Main hazards	Flammable, Corrosive
	GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H226, H302, H312, H314, H332
Precautionary statements	P210, P233, P240, P241, P242, P243, P260, P261, P264, P270, P271, P280, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P312, P304+P340, P305+P351+P338, P310, P312, P321, P322, P330, P363, P370+P378, P403+P235, P405, P501
NFPA 704 (fire diamond)	3 3 0
Flash point	31 °C (88 °F; 304 K)
Autoignition; temperature	275 °C (527 °F; 548 K)
Explosive limits	1.4%–11.2%
	Lethal dose or concentration (LD, LC):
LD50 (median dose)	1220 mg/kg (mammal, oral); 525 mg/kg (mouse, oral); 1050 mg/kg (rat, oral)
LC50 (median concentration)	365 ppm (mouse, 2 hr)
	NIOSH (US health exposure limits):
PEL (Permissible)	TWA 20 ppm (70 mg/m3) [skin]
REL (Recommended)	TWA 20 ppm (70 mg/m3) ST 30 ppm (105 mg/m3) [skin]
IDLH (Immediate danger)	1400 ppm
Safety data sheet (SDS)	hazard.com
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Morpholine is an organic chemical compound having the chemical formula O(C H₂CH₂)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 generates the salt morpholinium chloride. It is a colorless liquid with a weak, ammonia- or fish-like odor.^[6] The naming of morpholine is attributed to Ludwig Knorr, who incorrectly believed it to be part of the structure of morphine.^[7]

Production

Morpholine is often produced industrially by the dehydration of diethanolamine with concentrated sulfuric acid.^[8] Alternatively, it can be made from bis(2-chloroethyl)ether in a reaction with ammonia, by which also ammonium chloride is formed.

Morpholine is also produced industrially from diethylene glycol and ammonia, under high temperature and pressure, in the presence of hydrogen and a suitable catalyst.^[9]

Uses

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. Its 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

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.^[10]

It is commonly used to generate enamines.^[11]

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 (brand name 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

In nature, fruits make waxes to protect against insects and fungal contamination, but this can be lost as the fruit is cleaned. Hence a small amount of new wax, made from shellac, is applied to replace it. Morpholine is sometimes used as an emulsifier and solubility aid for this new coating.^[12] The European Union has forbidden the use of morpholine in fruit coating.^[13]^[14]

As a component in fungicides

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

References

^ National Institute for Occupational Safety and Health (2000). "Morpholine". International Chemical Safety Cards. Retrieved 5 November 2005.
^ International Union of Pure and Applied Chemistry (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. The Royal Society of Chemistry. p. 142. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.
^ ^a ^b ^c ^d ^e ^f NIOSH Pocket Guide to Chemical Hazards. "#0437". National Institute for Occupational Safety and Health (NIOSH).
^ Hall, H. K. (1957). "Correlation of the Base Strengths of Amines1". J. Am. Chem. Soc. 79 (20): 5441–5444. doi:10.1021/ja01577a030.
^ ^a ^b "Morpholine". Immediately Dangerous to Life or Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
^ "CDC - NIOSH Pocket Guide to Chemical Hazards - Morpholine". www.cdc.gov. Retrieved 4 January 2022.
^ F. Silversmith, Ernest; Nickon, Alex (2013-10-22). Organic Chemistry : Modern Coined Terms and Their Origins. Elsevier Science. p. 313. ISBN 978-1483145235.
^ Weissermel, Klaus; Arpe, Hans-Jürgen; Lindley, Charlet R.; Hawkins, Stephen (2003). "Chapter 7. Oxidation Products of Ethylene". Industrial Organic Chemistry. Wiley-VCH. pp. 159–161. ISBN 3-527-30578-5.
^ U.S. Patent 3151112, "Process for the preparation of morpholines" van 29 september 1964 aan Jefferson Chemical Company.
^ Lindsay Smith, J. R.; McKeer, L. C.; Taylor, J. M. (1993). "4-Chlorination of Electron-Rich Benzenoid Compounds: 2,4-Dichloromethoxybenzene". Organic Syntheses; Collected Volumes, vol. 8, p. 167.
^ Noyori, R.; Yokoyama, K.; Hayakawa, Y. (1988). "Cyclopentenones from α,α′-Dibromoketones and Enamines: 2,5-Dimethyl-3-Phenyl-2-Cyclopenten-1-one". Organic Syntheses; Collected Volumes, vol. 6, p. 520.
^ McGuire, Raymond G.; Dimitroglou, Dimitrios A. (1999). "Evaluation of Shellac and Sucrose Ester Fruit Coating Formulations that Support Biological Control of Post-harvest Grapefruit Decay". Bio-control Science and Technology. 9 (1): 53–65. Bibcode:1999BioST...9...53M. doi:10.1080/09583159929901.
^ "Morpholine". Scientific Analysis Laboratories Ltd. Archived from the original on 2012-04-26.
^ "Morpholine Issues in the United Kingdom". Northwest Horticultural Council. September 28, 2010. Archived from the original on April 26, 2012.