# Morpholine

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Not to be confused with [morphine](/source/Morphine) or [morpholino](/source/Morpholino).

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[2] Other names Diethylenimide oxide 1,4-Oxazinane Tetrahydro-1,4-oxazine Diethylene imidoxide Diethylene oximide Tetrahydro-p-oxazine Identifiers CAS Number 110-91-8 Y 3D model (JSmol) Interactive image Beilstein Reference 102549 ChEBI CHEBI:34856 Y ChEMBL ChEMBL276518 Y ChemSpider 13837537 Y ECHA InfoCard 100.003.469 EC Number 203-815-1 Gmelin Reference 1803 KEGG C14452 Y PubChem CID 8083 RTECS number QD6475000 UNII 8B2ZCK305O Y UN number 2054 CompTox Dashboard (EPA) DTXSID2025688 InChI InChI=1S/C4H9NO/c1-3-6-4-2-5-1/h5H,1-4H2 Y Key: YNAVUWVOSKDBBP-UHFFFAOYSA-N Y 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[3] 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)[3] Acidity (pKa) 8.36[4] (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, 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%[3] Lethal dose or concentration (LD, LC): LD50 (median dose) 1220 mg/kg (mammal, oral) 525 mg/kg (mouse, oral) 1050 mg/kg (rat, oral)[5] LC50 (median concentration) 365 ppm (mouse, 2 hr)[5] NIOSH (US health exposure limits): PEL (Permissible) TWA 20 ppm (70 mg/m3) [skin][3] REL (Recommended) TWA 20 ppm (70 mg/m3) ST 30 ppm (105 mg/m3) [skin][3] IDLH (Immediate danger) 1400 ppm[3] 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). Y verify (what is YN ?) Infobox references

Chemical compound

**Morpholine** is an [organic](/source/Organic_compound) [chemical compound](/source/Chemical_compound) having the [chemical formula](/source/Chemical_formula) [O](/source/Oxygen)([C](/source/Carbon)[H](/source/Hydrogen)2CH2)2[N](/source/Nitrogen)H. This [heterocycle](/source/Heterocycle) features both [amine](/source/Amine) and [ether](/source/Ether) [functional groups](/source/Functional_group). Because of the amine, morpholine is a [base](/source/Base_(chemistry)); its [conjugate acid](/source/Conjugate_acid) is called morpholinium. For example, treating morpholine with [hydrochloric acid](/source/Hydrochloric_acid) generates the [salt](/source/Salt_(chemistry)) 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](/source/Ludwig_Knorr), who incorrectly believed it to be part of the structure of [morphine](/source/Morphine).[7]

## Production

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

Morpholine is also produced industrially from [diethylene glycol](/source/Diethylene_glycol) and [ammonia](/source/Ammonia), under high temperature and pressure, in the presence of [hydrogen](/source/Hydrogen) and a suitable catalyst.[9]

## Uses

### Industrial applications

Morpholine is a common additive, in parts per million [concentrations](/source/Concentration), for [pH](/source/PH) adjustment in both [fossil fuel](/source/Fossil_fuel_power_plant) and [nuclear power plant](/source/Nuclear_power_plant) [steam](/source/Steam) systems. Morpholine is used because its [volatility](/source/Volatility_(chemistry)) is about the same as [water](/source/Water_(molecule)), so once it is added to the water, its concentration becomes distributed rather evenly in both the water and steam [phases](/source/Phase_(matter)). Its pH-adjusting qualities then become distributed throughout the steam plant to provide [corrosion protection](/source/Corrosion#Protection_from_corrosion). Morpholine is often used in conjunction with low concentrations of [hydrazine](/source/Hydrazine) or [ammonia](/source/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](/source/Oxygen) at the high [temperatures](/source/Temperature) and [pressures](/source/Pressure) in these steam systems.

### Organic synthesis

Morpholine undergoes most [chemical reactions](/source/Chemical_reaction) typical for other secondary [amines](/source/Amine), 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](/source/Piperidine). For this reason, it forms a stable [chloramine](/source/Chloramine).[10]

It is commonly used to generate [enamines](/source/Enamine).[11]

Morpholine is widely used in [organic synthesis](/source/Organic_synthesis). For example, it is a building block in the preparation of the antibiotic [linezolid](/source/Linezolid), the anticancer agent [gefitinib](/source/Gefitinib) (brand name Iressa) and the analgesic [dextromoramide](/source/Dextromoramide).

In research and in industry, the low cost and [polarity](/source/Polarity_(chemistry)) of morpholine lead to its common use as a [solvent](/source/Solvent) for chemical reactions.[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*]

### Agriculture

#### As a fruit coating

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

#### As a component in fungicides

Morpholine derivatives used as agricultural [fungicides](/source/Fungicide) in cereals are known as [ergosterol biosynthesis inhibitors](https://en.wikipedia.org/w/index.php?title=Ergosterol_biosynthesis_inhibitor&action=edit&redlink=1).

- [Amorolfine](/source/Amorolfine)

- [Fenpropimorph](/source/Fenpropimorph)

- [Tridemorph](/source/Tridemorph)

## See also

- [Morpholino](/source/Morpholino)

- [Piperidine](/source/Piperidine)

## References

1. **[^](#cite_ref-1)** National Institute for Occupational Safety and Health (2000). ["Morpholine"](https://www.cdc.gov/niosh/ipcsneng/neng0302.html). *International Chemical Safety Cards*. Retrieved 5 November 2005.

1. **[^](#cite_ref-2)** [International Union of Pure and Applied Chemistry](/source/International_Union_of_Pure_and_Applied_Chemistry) (2014). *Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013*. [The Royal Society of Chemistry](/source/Royal_Society_of_Chemistry). p. 142. [doi](/source/Doi_(identifier)):[10.1039/9781849733069](https://doi.org/10.1039%2F9781849733069). [ISBN](/source/ISBN_(identifier)) [978-0-85404-182-4](https://en.wikipedia.org/wiki/Special:BookSources/978-0-85404-182-4).

1. ^ [***a***](#cite_ref-PGCH_3-0) [***b***](#cite_ref-PGCH_3-1) [***c***](#cite_ref-PGCH_3-2) [***d***](#cite_ref-PGCH_3-3) [***e***](#cite_ref-PGCH_3-4) [***f***](#cite_ref-PGCH_3-5) NIOSH Pocket Guide to Chemical Hazards. ["#0437"](https://www.cdc.gov/niosh/npg/npgd0437.html). [National Institute for Occupational Safety and Health](/source/National_Institute_for_Occupational_Safety_and_Health) (NIOSH).

1. **[^](#cite_ref-4)** Hall, H. K. (1957). "Correlation of the Base Strengths of Amines1". *J. Am. Chem. Soc*. **79** (20): 5441–5444. [doi](/source/Doi_(identifier)):[10.1021/ja01577a030](https://doi.org/10.1021%2Fja01577a030).

1. ^ [***a***](#cite_ref-IDLH_5-0) [***b***](#cite_ref-IDLH_5-1) ["Morpholine"](https://www.cdc.gov/niosh/idlh/110918.html). *Immediately Dangerous to Life or Health Concentrations*. [National Institute for Occupational Safety and Health](/source/National_Institute_for_Occupational_Safety_and_Health).

1. **[^](#cite_ref-6)** ["CDC - NIOSH Pocket Guide to Chemical Hazards - Morpholine"](https://www.cdc.gov/niosh/npg/npgd0437.html). *www.cdc.gov*. Retrieved 4 January 2022.

1. **[^](#cite_ref-7)** F. Silversmith, Ernest; Nickon, Alex (2013-10-22). *Organic Chemistry : Modern Coined Terms and Their Origins*. Elsevier Science. p. 313. [ISBN](/source/ISBN_(identifier)) [978-1483145235](https://en.wikipedia.org/wiki/Special:BookSources/978-1483145235).

1. **[^](#cite_ref-weissermel_8-0)** Weissermel, Klaus; Arpe, Hans-Jürgen; Lindley, Charlet R.; Hawkins, Stephen (2003). "Chapter 7. Oxidation Products of Ethylene". *Industrial Organic Chemistry*. [Wiley-VCH](/source/Wiley-VCH). pp. 159–161. [ISBN](/source/ISBN_(identifier)) [3-527-30578-5](https://en.wikipedia.org/wiki/Special:BookSources/3-527-30578-5).

1. **[^](#cite_ref-9)** [U.S. Patent 3151112, "Process for the preparation of morpholines" van 29 september 1964 aan Jefferson Chemical Company.](https://patents.google.com/patent/US3151112)

1. **[^](#cite_ref-10)** Lindsay Smith, J. R.; McKeer, L. C.; Taylor, J. M. (1993). ["4-Chlorination of Electron-Rich Benzenoid Compounds: 2,4-Dichloromethoxybenzene"](https://www.orgsyn.org/demo.aspx?prep=CV8P0167). *[Organic Syntheses](/source/Organic_Syntheses)*; *Collected Volumes*, vol. 8, p. 167.

1. **[^](#cite_ref-11)** [Noyori, R.](/source/Ryoji_Noyori); Yokoyama, K.; Hayakawa, Y. (1988). ["Cyclopentenones from α,α′-Dibromoketones and Enamines: 2,5-Dimethyl-3-Phenyl-2-Cyclopenten-1-one"](https://www.orgsyn.org/demo.aspx?prep=CV6P0520). *[Organic Syntheses](/source/Organic_Syntheses)*; *Collected Volumes*, vol. 6, p. 520.

1. **[^](#cite_ref-12)** 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](/source/Bibcode_(identifier)):[1999BioST...9...53M](https://ui.adsabs.harvard.edu/abs/1999BioST...9...53M). [doi](/source/Doi_(identifier)):[10.1080/09583159929901](https://doi.org/10.1080%2F09583159929901).

1. **[^](#cite_ref-13)** ["Morpholine"](https://web.archive.org/web/20120426070141/http://www.salltd.co.uk/news_item.jsp?file=2010-09-29%20Morpholine%20residues%20detected%20in%20apples%20from%20Chile.html). Scientific Analysis Laboratories Ltd. Archived from [the original](http://www.salltd.co.uk/news_item.jsp?file=2010-09-29%20Morpholine%20residues%20detected%20in%20apples%20from%20Chile.html) on 2012-04-26.

1. **[^](#cite_ref-14)** ["Morpholine Issues in the United Kingdom"](https://web.archive.org/web/20120426070141/http://www.nwhort.org/UKCountryAlert.html). Northwest Horticultural Council. September 28, 2010. Archived from [the original](http://www.nwhort.org/UKCountryAlert.html) on April 26, 2012.

## External links

- Media related to [Morpholines](https://commons.wikimedia.org/wiki/Category:Morpholines) at Wikimedia Commons

Authority control databases: National Czech Republic

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Adapted from the Wikipedia article [Morpholine](https://en.wikipedia.org/wiki/Morpholine) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Morpholine?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.