P-Cresol
{{Short description|Chemical compound}}
{{DISPLAYTITLE:p-Cresol}}
{{use dmy dates|date=November 2022}}
{{chembox
| verifiedrevid = 477506207
| Name = p-Cresol
| ImageFile = Para-cresol-horizontal-2D-skeletal.png
| ImageName = Skeletal formula of p-cresol
| ImageFile1 = p-cresol-spaceFilling.png
| ImageSize1 = 150px
| ImageName1 = 3D model of p-cresol
| ImageFile2 = P-Cresol.jpg
| PIN = 4-Methylphenol
| SystematicName = 4-Methylbenzenol
| OtherNames = 4-Cresol
p-Cresol
4-Hydroxytoluene
p-Cresylic acid
1-Hydroxy-4-methylbenzene
| Section1 = {{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 106-44-5
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 16645
| RTECS = GO6475000
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01688
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 1MXY2UM8NV
| SMILES = Cc1ccc(O)cc1
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17847
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C01468
| ChemSpiderID = 13839082
| PubChem = 2879
| EC_number = 203-398-6
| Beilstein = 1305151
| Gmelin = 2779
| InChI = 1/C7H8O/c1-6-2-4-7(8)5-3-6/h2-5,8H,1H3
| InChIKey = IWDCLRJOBJJRNH-UHFFFAOYAN
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C7H8O/c1-6-2-4-7(8)5-3-6/h2-5,8H,1H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IWDCLRJOBJJRNH-UHFFFAOYSA-N
}}
| Section2 = {{Chembox Properties
| Appearance = colorless prismatic crystals
| Formula = C7H8O
| MolarMass = 108.13
| BoilingPtC = 201.8
| MeltingPtC = 35.5
| Density = 1.0347 g/ml
| RefractIndex = 1.5395
| Solubility = 2.4 g/100 ml at 40 °C
5.3 g/100 ml at 100 °C
| Solubility1 = miscible
| Solvent1 = ethanol
| Solubility2 = miscible
| Solvent2 = diethyl ether
| VaporPressure = 0.11 mmHg (25 °C)
| MagSus = {{val|-72.1e-6|u=cm3/mol}}
}}
| Section7 = {{Chembox Hazards
| ExternalSDS = [https://web.archive.org/web/20221104172905/https://www.emdmillipore.com/US/en/product/msds/MDA_CHEM-805223 External MSDS]
| FlashPtC = 86.1
| MainHazards = May be fatal if swallowed, inhaled, or absorbed through skin.
| NFPA-H = 3
| NFPA-F = 1
| NFPA-R = 0
| GHSPictograms = {{GHS05}}{{GHS06}}{{GHS08}}
| GHSSignalWord = Danger
| HPhrases = {{H-phrases|201|311|314|351|370|372|373|401|412}}
| PPhrases = {{P-phrases|201|202|260|264|270|273|280|281|301+310|301+330+331|302+352|303+361+353|304+340|305+351+338|307+311|308+313|310|312|314|321|322|330|361|363|405|501}}
| PEL = TWA 5 ppm (22 mg/m3) [skin]{{PGCH|0156}}
| LD50 = 207 mg/kg (oral, rat, 1969)
1800 mg/kg (oral, rat, 1944)
344 mg/kg (oral, mouse){{IDLH|cresol|Cresol (o, m, p isomers)}}
| REL = TWA 2.3 ppm (10 mg/m3)
}}
| Section8 = {{Chembox Related
| OtherFunction_label = phenols
| OtherFunction = o-cresol, m-cresol, phenol
}}
}}
para-Cresol, also 4-methylphenol, is an organic compound with the formula CH3C6H4(OH). It is a colourless solid that is widely used intermediate in the production of other chemicals. It is a derivative of phenol and is an isomer of o-cresol and m-cresol.{{Ullmann|doi=10.1002/14356007.a08_025 |title=Cresols and Xylenols |year=2000 |last1=Fiege |first1=Helmut | name-list-style = vanc |isbn=3-527-30673-0}}
Production
Together with many other compounds, p-cresol is conventionally extracted from coal tar, the volatilized materials obtained in the roasting of coal to produce coke. This residue contains a few percent by weight of phenol and cresols. Industrially, p-cresol is currently prepared mainly by a two-step route beginning with the sulfonation of toluene:{{cite journal|doi=10.15227/orgsyn.003.0037|title=p-Cresol|journal=Organic Syntheses|volume=3|pages=37|year=1923|author=W. W. Hartman}}
:CH3C6H5 + H2SO4 → CH3C6H4SO3H + H2O
Basic hydrolysis of the sulfonate salt gives the sodium salt of the cresol:
:CH3C6H4SO3H + 2 NaOH → CH3C6H4OH + Na2SO3 + H2O
Other methods for the production of p-cresol include chlorination of toluene followed by hydrolysis. In the cymene-cresol process, toluene is alkylated with propene to give p-cymene, which can be oxidatively dealkylated in a manner similar to the cumene process.
Applications
p-Cresol is consumed mainly in the production of antioxidants, such as butylated hydroxytoluene (BHT). The monoalkylated derivatives undergo coupling to give an extensive family of diphenol antioxidants. These antioxidants are valued because they are relatively low in toxicity and nonstaining.{{Cite web |date=April 2005 |title=meta- and para-Cresols |url=https://inchem.org/documents/sids/sids/m-p-cresols.pdf |url-status=dead |archive-url=https://web.archive.org/web/20171208161609/https://inchem.org/documents/sids/sids/m-p-cresols.pdf |archive-date=2017-12-08 |access-date=2022-11-04 |website=International Programme on Chemical Safety (IPCS INCHEM)}}{{Cite web |title=p-Cresol - Hazardous Agents |url=https://haz-map.com/Agents/16387?#:~:text=used,materials |access-date=2022-11-04 |website=Haz-Map: Information on Hazardous Chemicals and Occupational Diseases}}
Natural occurrences
= In humans =
p-Cresol is produced by bacterial fermentation of protein in the human large intestine. It is excreted in feces and urine,{{cite journal | vauthors = Hamer HM, De Preter V, Windey K, Verbeke K | title = Functional analysis of colonic bacterial metabolism: relevant to health? | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 302 | issue = 1 | pages = G1-9 | date = January 2012 | pmid = 22016433 | pmc = 3345969 | doi = 10.1152/ajpgi.00048.2011}} and is a component of human sweat that attracts female mosquitoes.{{cite journal | vauthors = Hallem EA, Nicole Fox A, Zwiebel LJ, Carlson JR | title = Olfaction: mosquito receptor for human-sweat odorant | journal = Nature | volume = 427 | issue = 6971 | pages = 212–213 | date = January 2004 | pmid = 14724626 | doi = 10.1038/427212a | bibcode = 2004Natur.427..212H| s2cid = 4419658 }}{{cite journal | vauthors = Linley JR | title = Laboratory tests of the effects of p-cresol and 4-methylcyclohexanol on oviposition by three species of Toxorhynchites mosquitoes | journal = Medical and Veterinary Entomology | volume = 3 | issue = 4 | pages = 347–52 | date = October 1989 | pmid = 2577519 | doi = 10.1111/j.1365-2915.1989.tb00241.x| s2cid = 1641506 }}
p-Cresol is a constituent of tobacco smoke.{{cite journal | vauthors = Talhout R, Schulz T, Florek E, van Benthem J, Wester P, Opperhuizen A | title = Hazardous compounds in tobacco smoke | journal = International Journal of Environmental Research and Public Health | volume = 8 | issue = 2 | pages = 613–28 | date = February 2011 | pmid = 21556207 | pmc = 3084482 | doi = 10.3390/ijerph8020613| doi-access = free }}
= In other species =
p-Cresol is a major component in pig odor.{{Cite web | first = Brendan | last = Borrell | date = 5 March 2009 | url = http://www.sciam.com/article.cfm?id=why-study-pig-odor | title = Why study pig odor? | work = Scientific American | access-date = 9 March 2009 | archive-date = 20 March 2021 | archive-url = https://web.archive.org/web/20210320042122/https://www.scientificamerican.com/article/why-study-pig-odor/ | url-status = live }} Temporal glands secretion examination showed the presence of phenol and p-cresol during musth in male elephants.{{cite journal | vauthors = Rasmussen LE, Perrin TE | title = Physiological correlates of musth: lipid metabolites and chemical composition of exudates | journal = Physiology & Behavior | volume = 67 | issue = 4 | pages = 539–49 | date = October 1999 | pmid = 10549891 | doi = 10.1016/S0031-9384(99)00114-6| s2cid = 21368454 }}{{cite journal |title=Musth in elephants |first1=Deepa |last1=Ananth | name-list-style = vanc|journal=Zoos' Print Journal |volume=15 |issue=5 |pages=259–62 |doi=10.11609/jott.zpj.14.4.259-62|date=May 2000 |doi-access=free}} It is one of the very few compounds to attract the orchid bee Euglossa cyanura and has been used to capture and study the species.{{cite journal |vauthors=Williams NH, Whitten WM |date=June 1983 |title=Orchid Floral Fragrances and Male Euglossine Bees: Methods and Advances in the Last Sesquidecade |journal=Biological Bulletin |volume=164 |issue=3 |pages=355–95 |jstor=1541248 |doi=10.2307/1541248 |url=https://www.biodiversitylibrary.org/part/35261 |access-date=2021-11-10 |archive-date=2020-06-05 |archive-url=https://web.archive.org/web/20200605121541/https://www.biodiversitylibrary.org/part/35261 |url-status=live }} p-Cresol is a component found in horse urine during estrus that can elicit the Flehmen response.{{cite journal | vauthors = Būda V, Mozūraitis R, Kutra J, Borg-Karlson AK | title = p-Cresol: a sex pheromone component identified from the estrous urine of mares | journal = Journal of Chemical Ecology | volume = 38 | issue = 7 | pages = 811–3 | date = July 2012 | pmid = 22592336 | doi = 10.1007/s10886-012-0138-2| s2cid = 14558317 }}