Acetophenone

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Acetophenone
Skeletal formula of the acetophenone molecule
Ball-and-stick model of the acetophenone molecule
Space-filling model of the acetophenone molecule
sample of Acetophenone
Names
Preferred IUPAC name
1-Phenylethan-1-one[1]
Other names
Acetophenone
Phenylethanone
Phenylacetone
Methyl phenyl ketone
Identifiers
3D model (JSmol)
Abbreviations ACP
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.002.462 Edit this at Wikidata
EC Number
  • 202-708-7
KEGG
RTECS number
  • AM5250000
UNII
UN number 1993
  • InChI=1S/C8H8O/c1-7(9)8-5-3-2-4-6-8/h2-6H,1H3 checkY
    Key: KWOLFJPFCHCOCG-UHFFFAOYSA-N checkY
  • InChI=1/C8H8O/c1-7(9)8-5-3-2-4-6-8/h2-6H,1H3
    Key: KWOLFJPFCHCOCG-UHFFFAOYAT
  • O=C(c1ccccc1)C
  • CC(=O)c1ccccc1
Properties
C8H8O
Molar mass 120.151 g·mol−1
Density 1.028 g/cm3
Melting point 19–20 °C (66–68 °F; 292–293 K)
Boiling point 202 °C (396 °F; 475 K)
5.5 g/L at 25 °C
12.2 g/L at 80 °C
-72.05·10−6 cm3/mol
Hazards
GHS labelling:
GHS07: Exclamation mark
Warning
H302, H319
P264, P270, P280, P301+P312, P305+P351+P338, P330, P337+P313, P501
NFPA 704 (fire diamond)
1
2
0
Flash point 77 °C (171 °F; 350 K)
Safety data sheet (SDS) MSDS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Acetophenone is the organic compound with the formula C6H5C(O)CH3 (also represented by the pseudoelement symbols PhAc or BzMe). It is the simplest aromatic ketone. This colorless, viscous liquid is a precursor to useful resins and fragrances.[2]

Production[edit]

Acetophenone is formed as a byproduct of the cumene process, the industrial route for the synthesis of phenol and acetone. In the Hock rearrangement of isopropylbenzene hydroperoxide, migration of a methyl group rather than the phenyl group gives acetophenone and methanol as a result of an alternate rearrangement of the intermediate:

C6H5C(CH3)2O2H → C6H5C(O)CH3 + CH3OH

The cumene process is conducted on such a large scale that even the small amount of acetophenone by-product can be recovered in commercially useful quantities.[2]

Acetophenone is also generated from ethylbenzene hydroperoxide. Ethylbenzene hydroperoxide is primarily converted to 1-phenylethanol (α-methylbenzyl alcohol) in the process with a small amount of by-product acetophenone. Acetophenone is recovered or hydrogenated to 1-phenylethanol which is then dehydrated to produce styrene.[2]

Uses[edit]

Precursor to resins[edit]

Commercially significant resins are produced from treatment of acetophenone with formaldehyde and a base. The resulting copolymers are conventionally described with the formula [(C6H5COCH)x(CH2)x]n, resulting from aldol condensation. These substances are components of coatings and inks. Modified acetophenone-formaldehyde resins are produced by the hydrogenation of the aforementioned ketone-containing resins. The resulting polyol can be further crosslinked with diisocyanates.[2] The modified resins are found in coatings, inks and adhesives.

Niche uses[edit]

Acetophenone is an ingredient in fragrances that resemble almond, cherry, honeysuckle, jasmine, and strawberry. It is used in chewing gum.[3] It is also listed as an approved excipient by the U.S. FDA.[4]

Laboratory reagent[edit]

In instructional laboratories,[5] acetophenone is converted to styrene in a two-step process that illustrates the reduction of carbonyls using hydride and the dehydration of alcohols:

4 C6H5C(O)CH3 + NaBH4 + 4 H2O → 4 C6H5CH(OH)CH3 + NaOH + B(OH)3 → C6H5CH=CH2

A similar two-step process is used industrially, but reduction step is performed by hydrogenation over a copper catalyst.[2]

C6H5C(O)CH3 + H2 → C6H5CH(OH)CH3

Being prochiral, acetophenone is also a popular test substrate for asymmetric hydrogenation experiments.

Drugs[edit]

Acetophenone is used for the synthesis of many pharmaceuticals.[6][7]

A Mannich reaction with dimethylamine and formaldehyde gives β-dimethylaminopropiophenone.[8] Using diethylamine instead gives the diethylamino analog.

Natural occurrence[edit]

Acetophenone occurs naturally in many foods including apple, cheese, apricot, banana, beef, and cauliflower. It is also a component of castoreum, the exudate from the castor sacs of the mature beaver.[9]

Pharmacology[edit]

In the late 19th and early 20th centuries, acetophenone was used in medicine.[10] It was marketed as a hypnotic and anticonvulsant under brand name Hypnone. The typical dosage was 0.12 to 0.3 milliliters.[11] It was considered to have superior sedative effects to both paraldehyde and chloral hydrate.[12] In humans, acetophenone is metabolized to benzoic acid, carbonic acid, and acetone.[13] Hippuric acid occurs as an indirect metabolite and its quantity in urine may be used to confirm acetophenone exposure,[14] although other substances, like toluene, also induce hippuric acid in urine.[15]

Toxicity[edit]

The LD50 is 815 mg/kg (oral, rats).[2] Acetophenone is currently listed as a Group D carcinogen indicating that there is no evidence at present that it causes cancer in humans.

References[edit]

  1. ^ Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 723. doi:10.1039/9781849733069-00648. ISBN 978-0-85404-182-4. The names acetophenone and benzophenone are retained only for general nomenclature, but no substitution is allowed.
  2. ^ a b c d e f Siegel, Hardo; Eggersdorfer, Manfred. "Ketones". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a15_077.
  3. ^ Burdock, George A. (2005), Fenaroli's Handbook of Flavor Ingredients (5th ed.), CRC Press, p. 15, ISBN 0-8493-3034-3, archived from the original on 2014-09-25
  4. ^ "Inactive Ingredient Search for Approved Drug Products". Archived from the original on 2013-05-04.
  5. ^ Wilen, Samuel H.; Kremer, Chester B.; Waltcher, Irving (1961). "Polystyrene—A multistep synthesis: For the undergraduate organic chemistry laboratory". J. Chem. Educ. 38 (6): 304–305. Bibcode:1961JChEd..38..304W. doi:10.1021/ed038p304.
  6. ^ Sittig, Marshall (1988). Pharmaceutical Manufacturing Encyclopedia. pp. 39, 177. ISBN 978-0-8155-1144-1.
  7. ^ Gadamasetti, Kumar; Tamim Braish (2007). Process Chemistry in the Pharmaceutical Industry, Volume 2. pp. 142–145. ISBN 978-0-8493-9051-7.
  8. ^ Maxwell, Charles E. (1943). "β-Dimethylaminopropiophenone Hydrochloride". Organic Syntheses. 23: 30.
  9. ^ Müller-Schwarze, D.; Houlihan, P. W. (April 1991). "Pheromonal activity of single castoreum constituents in beaver, Castor canadensis". Journal of Chemical Ecology. 17 (4): 715–34. doi:10.1007/BF00994195. PMID 24258917. S2CID 29937875.
  10. ^ Budavari, Susan, ed. (1996), The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (12th ed.), Merck, ISBN 0911910123
  11. ^ Bartholow, Roberts (1908). A Practical Treatise on Materia Medica and Therapeutics. Appleton & Co.
  12. ^ Norman, Conolly (1887). "Cases illustrating the sedative effects of aceto-phenone". Journal of Mental Science. 32: 519. doi:10.1192/bjp.32.140.519.
  13. ^ "Hypnone – The new hypnotic". Journal of the American Medical Association. 5 (23): 632. 1885. doi:10.1001/jama.1885.02391220016006.
  14. ^ CID 7410 from PubChem
  15. ^ "The Netherlands Center for Occupational Diseases (NCvB): toluene (Dutch)" (PDF). beroepsziekten.nl. Retrieved 19 April 2018.