Cyclohexanone

{{chembox

|Watchedfields = changed

|verifiedrevid = 443547421

|Reference={{Cite web |title=ICSC 0425 – CYCLOHEXANONE |url=https://inchem.org/documents/icsc/icsc/eics0425.htm |access-date=2022-08-24 |website=inchem.org}}{{Cite web |title=CDC – NIOSH Pocket Guide to Chemical Hazards – Cyclohexanone |url=https://www.cdc.gov/niosh/npg/npgd0166.html |access-date=August 24, 2022|publisher=Centers for Disease Control and Prevention (CDC)}}

|Name = Cyclohexanone

|ImageFileL1_Ref = {{chemboximage|correct|??}}

|ImageFileL1 = Cyclohexanone.svg

|ImageNameL1 = Skeletal formula of cyclohexanone

|ImageSizeL1 = 80px

|ImageFileR1 = Cyclohexanone-from-xtal-top-view-3D-bs-17.png

|ImageNameR1 = Ball-and-stick model of cyclohexanone

|ImageSizeR1 = 125px

|ImageFileL2 = Cyclohexanone-conformation-2D-skeletal.png

|ImageNameL2 = Skeletal formula viewed side-on, showing the non-planar conformation

|ImageSizeL2 = 125px

|ImageFileR2 = Cyclohexanone-from-xtal-side-view-3D-bs-17.png

|ImageNameR2 = Ball-and-stick model of cyclohexanone viewed side-on, showing the non-planar conformation

|ImageSizeR2 = 125px

|PIN = Cyclohexanone

|OtherNames= oxocyclohexane, pimelic ketone, ketohexamethylene, cyclohexyl ketone, ketocyclohexane, hexanon, Hydrol-O, Sextone, K, Anone

|Section1={{Chembox Identifiers

|DrugBank_Ref = {{drugbankcite|correct|drugbank}}

|DrugBank = DB02060

|ChEBI_Ref = {{ebicite|correct|EBI}}

|ChEBI = 17854

|SMILES = C1CCC(=O)CC1

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|ChemSpiderID = 7679

|PubChem = 7967

|UNII_Ref = {{fdacite|correct|FDA}}

|UNII = 5QOR3YM052

|KEGG_Ref = {{keggcite|correct|kegg}}

|KEGG = C00414

|InChI = 1/C6H10O/c7-6-4-2-1-3-5-6/h1-5H2

|InChIKey = JHIVVAPYMSGYDF-UHFFFAOYAY

|ChEMBL_Ref = {{ebicite|correct|EBI}}

|ChEMBL = 18850

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChI = 1S/C6H10O/c7-6-4-2-1-3-5-6/h1-5H2

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = JHIVVAPYMSGYDF-UHFFFAOYSA-N

|CASNo_Ref = {{cascite|correct|CAS}}

|CASNo = 108-94-1

|EC_number = 203-631-1

}}

|Section2={{Chembox Properties

|Formula = C₆H₁₀O

|MolarMass = 98.15 g/mol

|Appearance = Colorless liquid

|Odor = Peppermint or acetone-like

|Density = 0.9478 g/mL, liquid

|Solubility = 8.6 g/100 mL (20 °C)

|Solvent = all organic solvents

|SolubleOther = Miscible

|LogP = 0.81

|MeltingPtC = −47

|MeltingPt_ref = {{cite web|url=http://www.sigmaaldrich.com/catalog/product/SIAL/398241|publisher=Sigma-Aldrich|title=Cyclohexanone}}

|BoilingPtC = 155.65

|Viscosity = 2.02 cP at 25 °C{{cite book |author=Ch. Wohlfarth |chapter=Viscosity of cyclohexanone |editor=M.D. Lechner |title=Viscosity of Pure Organic Liquids and Binary Liquid Mixtures · Supplement to IV/18 |doi=10.1007/978-3-540-75486-2_192 |publisher=Springer-Verlag}}

|RefractIndex = 1.447

|VaporPressure = 5 mmHg (20 °C)

|MagSus = −62.04·10⁻⁶ cm³/mol

}}

|Section3={{Chembox Thermochemistry

|DeltaHf = −270.7 kJ·mol⁻¹

|DeltaHc = −3519.3 kJ·mol⁻¹

|Entropy = +229.03 J·K⁻¹·mol⁻¹

}}

|Section4={{Chembox Hazards

|FlashPtC = 44

|AutoignitionPtC = 420

|ExploLimits = 1.1–9.4%

|NFPA-H = 1

|NFPA-F = 2

|NFPA-R = 0

|GHSPictograms = {{GHS02}}{{GHS05}}{{GHS07}}

|GHSSignalWord = Danger{{Sigma-Aldrich|Sial|id=398241|name=Cyclohexanone|access-date=2022-03-17}}

|HPhrases = {{H-phrases|226|302|305|312|332|315|318}}

|PPhrases = {{P-phrases|280|305+351+338}}

|PEL = TWA 50 ppm (200 mg/m³){{PGCH|0166}}

|IDLH = 700 ppm

|REL = TWA 25 ppm (100 mg/m³) [skin]

|LD50 = 1200 mg/kg (cat, orally); 2362 mg/kg (rat, orally)Cyclohexanone: toxicity for animals and humans

|LC50 = 8000 ppm (rat, 4 hr){{IDLH|108941|Cyclohexanone}}

|LCLo = 4706 ppm (mouse, 1.5 hr)

}}

|Section5={{Chembox Related

|OtherFunction_label = ketones

|OtherFunction = Cyclopentanone, cycloheptanone

|OtherCompounds = Cyclohexanol

}}

Cyclohexanone is the organic compound with the formula (CH₂)₅CO. The molecule consists of six-carbon cyclic molecule with a ketone functional group. This colorless oily liquid{{cite web|title=Cyclohexanone (CID 7967)|url=https://pubchem.ncbi.nlm.nih.gov/compound/7967#:~:text=is%20a%20colorless,%20liquid|website=PubChem}} has a sweet odor reminiscent of benzaldehyde. Over time, samples of cyclohexanone assume a pale yellow color.{{cite web|publisher=PubChem|title=Cyclohexanone (CID 7967)|url=https://pubchem.ncbi.nlm.nih.gov/compound/7967#:~:text=pale,liquid}}

Cyclohexanone is slightly soluble in water and miscible with common organic solvents. Millions of tonnes are produced annually, mainly as a precursor to nylon.{{cite book|last=Musser|first=Michael T.|chapter=Cyclohexanol and Cyclohexanone|date=October 15, 2011|chapter-url=https://onlinelibrary.wiley.com/doi/10.1002/14356007.a08_217.pub2|title=Ullmann's Encyclopedia of Industrial Chemistry|pages=|publisher=Wiley-VCH Verlag GmbH & Co. KgaA|location=Weinheim, Germany|doi=10.1002/14356007.a08_217.pub2 |oclc=46878292|isbn=978-3-527-30673-2|access-date=January 27, 2009}}

History and synthesis

The compound was discovered by {{Ill|Edmund Drechsel|de}} in 1888 among the products of AC electrolysis of slightly acidified water solutions of phenol. He named it hydrophenoketone and correctly suggested that phenol was first hydrogenated by electrolytic hydrogen to cyclohexanol, which he wasn't able to isolate, and then oxidized by electrolytic oxygen.{{Cite Q|Q56441554}}{{Cite journal |last=Perkin |first=William Henry |last2=Plant |first2=Sydney Glenn Preston |date=1921 |title=Derivatives of tetrahydrocarbazole |url=https://pubs.rsc.org/en/Content/ArticleLanding/1921/CT/CT9211901825 |journal=Journal of the Chemical Society, Transactions |language=en |volume=119 |issue=0 |pages=1825–1839 |doi=10.1039/CT9211901825 |issn=0368-1645}}

=Laboratory synthesis=

Cyclohexanone can be prepared from cyclohexanol by oxidation with chromium trioxide (Jones oxidation). An alternative method utilizes the safer and more readily available oxidant sodium hypochlorite.{{cite web |title=Oxidation of Cyclohexanol to Cyclohexanone |url=http://www2.volstate.edu/CHEM/2010/Labs/Cyclohexanone.html |archive-url=https://web.archive.org/web/20120426194932/http://www2.volstate.edu/CHEM/2010/Labs/Cyclohexanone.html |archive-date=2012-04-26 |access-date=2012-07-09}}{{cite journal |last1=Mohrig |first1=Jerry R. |last2=Nienhuis |first2=David M. |last3=Linck |first3=Catherine F. |last4=Van Zoeren |first4=Carol |last5=Fox |first5=Brian G. |last6=Mahaffy |first6=Peter G. |date=June 1985 |title=The design of laboratory experiments in the 1980's: A case study on the oxidation of alcohols with household bleach |journal=Journal of Chemical Education |volume=62 |issue=6 |pages=519 |doi=10.1021/ed062p519}}

= Industrial production =

Cyclohexanone is produced by the oxidation of cyclohexane in air, typically using cobalt catalysts:

:C₆H₁₂ + O₂ → (CH₂)₅CO + H₂O

This process forms cyclohexanol as a by-product, and this mixture, called "KA Oil" for ketone-alcohol oil, is the main feedstock for the production of adipic acid. The oxidation involves radicals and the hydroperoxide C₆H₁₁O₂H as an intermediate. In some cases, purified cyclohexanol, obtained by hydration of cyclohexene, is the precursor. Alternatively, cyclohexanone can be produced by the partial hydrogenation of phenol:

:C₆H₅OH + 2 H₂ → (CH₂)₅CO

This process can also be adjusted to favor the formation of cyclohexanol.

ExxonMobil developed a process in which benzene is hydroalkylated to cyclohexylbenzene. This latter product is oxidized to a hydroperoxide and then cleaved into phenol and cyclohexanone.{{cite web |url=https://www.acs.org/content/acs/en/pressroom/cutting-edge-chemistry/what-s-new-in-phenol-production-.html |title=What's New in Phenol Production? |last=Plotkin |first=Jeffrey S. |publisher=American Chemical Society |date=2016-03-21 |access-date=2019-10-27 |archive-url=https://web.archive.org/web/20191027122212/https://www.acs.org/content/acs/en/pressroom/cutting-edge-chemistry/what-s-new-in-phenol-production-.html |archive-date=2019-10-27 }} Therefore, this newer process without producing the acetone by-product appears attractive and is similar to the cumene process as a hydroperoxide is formed and then decomposed to yield two key products.{{cite web |url=http://www.essentialchemicalindustry.org/chemicals/phenol.html |title=Phenol – The essential chemical industry online |date=2017-01-11 |access-date=2019-10-27}}

Uses

The great majority of cyclohexanone is consumed in the production of precursors to Nylon 6,6 and Nylon 6. About half of the world's supply is converted to adipic acid, one of two precursors for nylon 6,6. For this application, the KA oil (see above) is oxidized with nitric acid. The other half of the cyclohexanone supply is converted to cyclohexanone oxime. In the presence of sulfuric acid catalyst, the oxime rearranges to caprolactam, a precursor to nylon 6:

::340px

=Other reactions=

In addition to the large scale reactions conducted in service of the polymer industry, many reactions have been developed for cyclohexanone.

In the presence of light, it undergoes alpha-chlorination to give 2-chlorocyclohexanone.{{cite journal|title=2-chlorocyclohexanone |author=M. S. Newman |author2=M. D. Farbman |author3=H. Hipsher|journal=Org. Synth.|year=1945|volume=25|page=22|doi=10.15227/orgsyn.025.0022}} It forms a trimethylsilylenol ether upon treatment with trimethylsilylchloride in the presence of base.{{cite journal|title=Alkylations Using Hexacarbonyl(Propargylium)dicobalt Salts: 2-(1-methyl-2-propynyl)cyclohexanone |author=Valsamma Varghese |author2=Manasi Saha |author3=Kenneth M. Nicholas|journal=Org. Synth.|year=1989|volume=67|page=141|doi=10.15227/orgsyn.067.0141}}

It forms an enamine with pyrrolidine.{{cite journal|title=2,2-(Trimethylenedithio)cyclohexanone |author=R. B. Woodward |author2=I. J. Pachter |author3=M. L. Scheinbaum|journal=Org. Synth.|year=1974|volume=54|page=39|doi=10.15227/orgsyn.054.0039}}

Treatment with nitrosyl chloride and ethanol in sulfur dioxide gives the oximinecarboxylic ester:{{March6th|page=1736}}

:{{chem2|(CH2)5CO + C2H5OH + NOCl -> HON\dCH(CH2)4CO2C2H5 + HCl}}

=Illicit use=

Cyclohexanone has been used in the illicit production of phencyclidine and its analogs{{cite journal|last1=Shulgin|first1=A. T.|last2=MacLean|first2=D. E.|title=Illicit Synthesis of Phencyclidine (PCP) and Several of Its Analogs|journal=Clinical Toxicology|date=25 September 2008|volume=9|issue=4|pages=553–560|doi=10.3109/15563657608988157|pmid=975751 }} and is often subject to purchase restrictions, such as being listed on the Special Surveillance List in the US.{{cite web|url=http://www.deadiversion.usdoj.gov/chem_prog/advisories/surveillance.htm |title=Special Surveillance List of Chemicals, Products, Materials and Equipment Used in the Clandestine Production of Controlled Substances or Listed Chemicals |archive-url=https://web.archive.org/web/20110420054619/http://www.deadiversion.usdoj.gov/chem_prog/advisories/surveillance.htm |archive-date=April 20, 2011 }}

Safety

Like cyclohexanol, cyclohexanone is not carcinogenic and is moderately toxic, with a TLV of 25 ppm for the vapor. It is an irritant.

References

Category:IARC Group 3 carcinogens