Trifluoroacetic acid: Difference between revisions

{{use dmy dates |date=December 2021}}

|Verifiedfields = changed

|Watchedfields = changed

|verifiedrevid = 411555727

|Name = Trifluoroacetic acid

|ImageFileL1 = Trifluoroacetic acid.svg

|ImageFileR1 = Trifluoroacetic-acid-3D-vdW.png

|ImageFile2 = Trifluoroacetic-acid-elpot.png<!-- what is this? -->

|ImageSize2 = 120px

|ImageFile3 = Trifluoro acetic acid 1ml.jpg

|PIN = Trifluoroacetic acid <!-- the locant ‘2’ for acetic acid is not cited, see P-14.3.4.6 of Nomenclature of Organic Chemistry – IUPAC Recommendations and Preferred Names 2013 (Blue Book) -->

|OtherNames = 2,2,2-Trifluoroacetic acid<br />2,2,2-Trifluoroethanoic acid<br />Perfluoroacetic acid<br />Trifluoroethanoic acid<br />TFA

|Section1 = {{Chembox Identifiers

|CASNo = 76-05-1

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

|Beilstein = 742035

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

|ChEBI = 45892

|SMILES = FC(F)(F)C(=O)O

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

|ChemSpiderID = 10239201

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

|UNII = E5R8Z4G708

|PubChem = 6422

|InChI = 1/C2HF3O2/c3-2(4,5)1(6)7/h(H,6,7)

|InChIKey = DTQVDTLACAAQTR-UHFFFAOYAP

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

|ChEMBL = 506259

|Gmelin = 2729

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

|StdInChI = 1S/C2HF3O2/c3-2(4,5)1(6)7/h(H,6,7)

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

|StdInChIKey = DTQVDTLACAAQTR-UHFFFAOYSA-N

|RTECS = AJ9625000

}}

|Section2 = {{Chembox Properties

|Formula = C₂HF₃O₂

|C=2 | H = 1 | F = 3 | O = 2 <!-- MolarMass is calculated -->

|Appearance = colorless liquid

|Density = 1.489 g/cm³, 20&nbsp;°C

|Solubility = miscible

|MeltingPtC = -15.4

|Odor = Pungent/Vinegar

|BoilingPtC = 72.4

|VaporPressure = {{convert|0.0117|bar|kPa|abbr=on}} at 20&nbsp;°C<ref name="Welcome to the NIST WebBook">{{cite journal | title=Trifluoroacetic acid | website=Welcome to the NIST WebBook | year=1962 | volume=10 | issue=11–12 | pages=629–633 | url=https://webbook.nist.gov/cgi/cbook.cgi?ID=C76051&Mask=4&Type=ANTOINE&Plot=on | access-date=2020-03-01| last1=Kreglewski | first1=A. }}</ref>

|pKa = 0.52 <ref> {{cite book |editor3=Thomas J. Bruno |editor1=W. M. Haynes. |editor2=David R. Lide |title=[[CRC Handbook of Chemistry and Physics]] |date=2016–2017 |pages=954–963 |publisher=CRC Press |isbn=978-1-4987-5429-3}}</ref>

|ConjugateBase = [[trifluoroacetate]]

|MagSus = -43.3·10⁻⁶ cm³/mol

}}

|Section3 = {{Chembox Hazards

|ExternalSDS = [http://hazard.com/msds/mf/baker/baker/files/t5525.htm External MSDS]

|MainHazards = Highly corrosive

|NFPA-H = 3

|NFPA-R = 1

|NFPA-F = 1

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

|GHSSignalWord = Danger

|HPhrases = {{H-phrases|314|332|412}}

|PPhrases = {{P-phrases|260|261|264|271|273|280|301+330+331|303+361+353|304+312|304+340|305+351+338|310|312|321|363|405|501}}

}}

|Section4 = {{Chembox Related

|OtherFunction = [[Heptafluorobutyric acid]]<br />[[Perfluorooctanoic acid]]<br />[[Perfluorononanoic acid]]

|OtherFunction_label = perfluorinated acids

|OtherCompounds = [[Acetic acid]]<br />[[Trichloroacetic acid]]

}}

'''Trifluoroacetic acid''' ('''TFA''') is an [[organofluorine]] compound with the [[chemical formula]] CF₃CO₂H. It is a [[haloacetic acid]], with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms. It is a colorless liquid with a [[vinegar]]-like odor. TFA is a stronger acid than acetic acid, having an [[acid ionisation constant]], ''K''_a, that is approximately 34,000 times higher,<ref>'''Note:''' Calculated from the ratio of the [[acid dissociation constant|''K''_a]] values for TFA (p''K''_a&nbsp;=&nbsp;0.23) and acetic acid (p''K''_a&nbsp;=&nbsp;4.76)</ref> as the highly [[electronegative]] fluorine atoms and consequent [[Electron-withdrawing functional group|electron-withdrawing nature]] of the [[trifluoromethyl]] group weakens the oxygen-hydrogen bond (allowing for greater acidity) and stabilises the [[anion]]ic [[conjugate base]]. TFA is widely used in [[organic chemistry]] for various purposes.

TFA is prepared industrially by the [[electrofluorination]] of [[acetyl chloride]] or [[acetic anhydride]], followed by hydrolysis of the resulting trifluoroacetyl fluoride:<ref name=Ullmann>{{Ullmann |author=G. Siegemund |author2=W. Schwertfeger |author3=A. Feiring |author4=B. Smart |author5=F. Behr |author6=H. Vogel |author7=B. McKusick | title = Fluorine Compounds, Organic | doi = 10.1002/14356007.a11_349}}</ref>

:{{chem|CH|3|COCl}} + 4 {{chem|HF}} → {{chem|CF|3|COF}} + 3 {{chem|H|2}} + {{chem|HCl}}

:{{chem|CF|3|COF}} + {{chem|H|2|O}} → {{chem|CF|3|COOH}} + {{chem|HF}}

Where desired, this compound may be dried by addition of [[trifluoroacetic anhydride]].<ref>{{cite book | doi = 10.1016/B978-1-85617-567-8.50012-3 | chapter = Chapter 4 - Purification of Organic Chemicals | title = Purification of Laboratory Chemicals | edition = 6th |author1=Wilfred L.F. Armarego |author2=Christina Li Lin Chai | year = 2009 | pages = 88–444 | isbn = 978-1-85617-567-8 |name-list-style=amp }}</ref>

An older route to TFA proceeds via the oxidation of 1,1,1-trifluoro-2,3,3-trichloropropene with [[potassium permanganate]]. The trifluorotrichloropropene can be prepared by [[Swarts fluorination]] of [[hexachloropropene]].<ref>{{cite book|url=https://library.sciencemadness.org/library/books/gergel_isopropyl_bromide.pdf|title=Excuse me sir, would you like to buy a kilo of isopropyl bromide?|first=Max&nbsp;G.|last=Gergel|author-link=Max Gergel|date=March 1977|publisher=Pierce Chemical|pages=88–90}}</ref>

[[File:Trifluoroacetic acid in a beaker.jpg|thumb|left|Trifluoroacetic acid in a beaker]]

TFA is the precursor to many other fluorinated compounds such as [[trifluoroacetic anhydride]], [[trifluoroperacetic acid]], and [[2,2,2-trifluoroethanol]].<ref name = Ullmann/> It is a [[reagent]] used in [[organic synthesis]] because of a combination of convenient properties: volatility, solubility in organic solvents, and its strength as an acid.<ref>{{cite encyclopedia|year=2004|encyclopedia=Encyclopedia of Reagents for Organic Synthesis|publisher=J. Wiley & Sons|location=New York|editor=L. Paquette|doi=10.1002/047084289X.rt236.pub2|isbn=978-0-471-93623-7|author2=Nichols, P. J.|author1=Eidman, K. F.|chapter=Trifluoroacetic Acid|hdl=10261/236866|hdl-access=free}}</ref> TFA is also less oxidizing than [[sulfuric acid]] but more readily available in anhydrous form than many other acids. One complication to its use is that TFA forms an [[azeotrope]] with water (b. p.&nbsp;105&nbsp;°C).

TFA is popularly used as a strong acid to remove [[protecting group]]s such as [[t-butoxycarbonyl|Boc]] used in organic chemistry and [[peptide synthesis]].<ref>{{cite journal | doi = 10.1111/j.1399-3011.1978.tb02896.x | title = Removal of t-Butyl and t-Butoxycarbonyl Protecting Groups with Trifluoroacetic acid | year = 1978 | last1 = Lundt | first1 = Behrend F. | last2 = Johansen | first2 = Nils L. | last3 = Vølund | first3 = Aage | last4 = Markussen | first4 = Jan | journal = International Journal of Peptide and Protein Research | volume = 12 | issue = 5 | pages = 258–268 | pmid = 744685}}</ref><ref>{{cite book | doi = 10.1002/9783527631827.ch1 | chapter = 1. Protection Reactions | author = Andrew B. Hughes |editor1=Vommina V. Sureshbabu |editor2=Narasimhamurthy Narendra | volume = 4 | title = Amino Acids, Peptides and Proteins in Organic Chemistry: Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis| year = 2011 | pages = 1–97 | isbn = 978-3-527-63182-7}}</ref>

At a low concentration, TFA is used as an ion pairing agent in [[liquid chromatography]] (HPLC) of organic compounds, particularly [[peptide]]s and small [[protein]]s. TFA is a versatile solvent for [[NMR spectroscopy]] (for materials stable in acid). It is also used as a calibrant in mass spectrometry.<ref>{{cite journal | doi = 10.1021/ac00193a027 | title = Tuning and calibration in thermospray liquid chromatography/mass spectrometry using trifluoroacetic acid cluster ions | year = 1989 | last1 = Stout | first1 = Steven J. | last2 = Dacunha | first2 = Adrian R. | journal = Analytical Chemistry | volume = 61 | pages = 2126 | issue = 18}}</ref>

TFA is used to produce trifluoroacetate salts.<ref>{{cite journal |author1=O. Castano |author2=A. Cavallaro |author3=A. Palau |author4=J. C. Gonzalez |author5=M. Rossell |author6=T. Puig |author7=F. Sandiumenge |author8=N. Mestres |author9=S. Pinol |author10=A. Pomar |author11=X. Obradors |name-list-style=amp | title = High quality YBa₂Cu₃O₇ thin films grown by trifluoroacetates metal-organic deposition | journal = Superconductor Science and Technology | year = 2003 | volume = 16 | issue = 1 | pages = 45–53 | doi = 10.1088/0953-2048/16/1/309 | bibcode = 2003SuScT..16...45C |s2cid=250765145 }}</ref>

==Safety==

Trifluoroacetic acid is a corrosive strong acid<ref>{{cite journal |last1=Henne |first1=Albert L |last2=Fox |first2=Charles J |year=1951 |title=Ionization constants of fluorinated acids |url=http://rave.ohiolink.edu/etdc/view?acc_num=osu1486550192262315 |journal=[[Journal of the American Chemical Society]] |volume=73 |issue=5 |pages=2323–2325 |doi=10.1021/ja01149a122}}</ref> but it does not pose the hazards associated with [[Hydrofluoric acid#Health and safety|hydrofluoric acid]] because the [[carbon-fluorine bond]] is not [[lability|labile]]. TFA is harmful when inhaled, causes severe skin burns and is toxic for aquatic organisms even at low concentrations.

TFA's reaction with bases and metals, especially [[light metal]]s, is strongly exothermic. The reaction with [[lithium aluminium hydride]] (LAH) results in an explosion.<ref name="Merck">Safety data sheet for [http://www.emdmillipore.com/INTERSHOP/web/WFS/Merck-CH-Site/en_US/-/CHF/ShowDocument-File?ProductSKU=MDA_CHEM-808260&DocumentId=808260_SDS_EN_US.PDF&DocumentType=MSD&Language=EN&Country=US Trifluoroacetic acid] (PDF) from EMD Millipore, revision date 10/27/2014.</ref>

TFA is a metabolic breakdown product of the volatile anaesthetic agent [[halothane]]. It is thought to be responsible for halothane induced [[hepatitis]].<ref>{{Citation|title=Halothane|date=2012|url=http://www.ncbi.nlm.nih.gov/books/NBK548151/|work=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury|place=Bethesda (MD)|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|pmid=31643481|access-date=2021-07-15}}</ref>

==Environment==

No known natural processes generate trifluoroacetic acid.<ref>{{Cite journal |last1=Joudan |first1=Shira |last2=De Silva |first2=Amila O. |last3=Young |first3=Cora J. |date=2021 |title=Insufficient evidence for the existence of natural trifluoroacetic acid |journal=Environmental Science: Processes & Impacts |language=en |volume=23 |issue=11 |pages=1641–1649 |doi=10.1039/D1EM00306B |pmid=34693963 |issn=2050-7887|hdl=10315/40884 |s2cid=239768006 |hdl-access=free }}</ref> In the environment, trifluoroacetic acid may be formed by [[photooxidation]] of the commonly used [[refrigerant]] [[1,1,1,2-tetrafluoroethane]] (R-134a).{{cn|date=January 2024}} Moreover, it is formed as an atmospheric degradation product of almost all fourth-generation synthetic refrigerants, also called [[Hydrofluoroolefin|hydrofluoroolefins]] (HFO), such as [[2,3,3,3-tetrafluoropropene]].{{cn|date=January 2024}}

Trifluoroacetic acid [[Persistent organic pollutant|degrades very slowly]] in the environment, and has been found in increasing amounts as a contaminant in water, soil, food, and the human body.<ref>https://www.theguardian.com/environment/2024/may/01/rapidly-rising-levels-of-tfa-forever-chemical-alarm-experts</ref> Median concentrations of a few micrograms per liter have been found in beer and tea.<ref>{{Cite journal|last=Marco Scheurer, Karsten Nödler|date=2021|title=Ultrashort-chain perfluoroalkyl substance trifluoroacetate (TFA) in beer and tea – An unintended aqueous extraction|journal=Food Chemistry|volume=351|pages=129304|doi=10.1016/j.foodchem.2021.129304|pmid=33657499|s2cid=232115008|issn=0308-8146}}</ref> Sea water contains about 200 ng of TFA per liter.<ref>{{cite journal | pmid = 11811478 | volume=36 | issue=1 | title=Trifluoroacetate in ocean waters |date=January 2002 | journal=Environ. Sci. Technol. | pages=12–5|bibcode = 2002EnST...36...12P |doi = 10.1021/es0221659 | doi-access= | last1=Frank | first1=H. | last2=Christoph | first2=E. H. | last3=Holm-Hansen | first3=O. | last4=Bullister | first4=J. L. }}</ref><ref>{{cite journal | pmid = 16190212 | volume=39 | issue=17 | title=Trifluoroacetate profiles in the Arctic, Atlantic, and Pacific Oceans |date=September 2005 | journal=Environ. Sci. Technol. | pages=6555–60|bibcode = 2005EnST...39.6555S |doi = 10.1021/es047975u | last1=Scott | first1=B. F. | last2=MacDonald | first2=R. W. | last3=Kannan | first3=K. | last4=Fisk | first4=A. | last5=Witter | first5=A. | last6=Yamashita | first6=N. | last7=Durham | first7=L. | last8=Spencer | first8=C. | last9=Muir | first9=D. C. G. }}</ref><ref>{{Cite journal|last1=Frank|first1=Hartmut|last2=Christoph|first2=Eugen H.|last3=Holm-Hansen|first3=Osmund|last4=Bullister|first4=John L.|date=2002|title=Trifluoroacetate in Ocean Waters|journal=Environmental Science & Technology|volume=36|issue=1|pages=12–15|doi=10.1021/es0101532|pmid=11811478|bibcode=2002EnST...36...12F|issn=0013-936X}}</ref> No biodegradation mechanism for the compound is known in water,<ref name="LMU2014">{{cite news |date=2014 |title=Refreshingly cool, potentially toxic |url=http://www.en.uni-muenchen.de/news/newsarchiv/2014/kornath_refrigerant.html |access-date=26 July 2018 |work=Ludwig-Maximilians-Universität (LMU) Munich}}</ref> although [[biotransformation]] apparently [[decarboxylation|decarboxylates]] the acid to [[fluoroform]].<ref>Kirschner, E., Chemical and Engineering News 1994, 8.</ref>

Trifluoroacetic acid is mildly [[phytotoxic]].<ref>{{cite journal |last1=Boutonnet |first1=Jean Charles |last2=Bingham |first2=Pauline |last3=Calamari |first3=Davide |last4=Rooij |first4=Christ de |last5=Franklin |first5=James |last6=Kawano |first6=Toshihiko |last7=Libre |first7=Jean-Marie |last8=McCul-Loch |first8=Archie |last9=Malinverno |first9=Giuseppe |last10=Odom |first10=J Martin |last11=Rusch |first11=George M |last12=Smythe |first12=Katie |last13=Sobolev |first13=Igor |last14=Thompson |first14=Roy |last15=Tiedje |first15=James M |year=1999 |title=Environmental risk assessment of trifluoroacetic acid |journal=International Journal of Human and Ecological Risk Assessment |volume=5 |issue=1 |pages=59–124 |bibcode=1999HERA....5...59B |doi=10.1080/10807039991289644}}</ref>

==See also==

* [[Fluoroacetic acid]]{{snd}}highly toxic but naturally occurring [[rodenticide]] CH₂FCOOH

* [[Difluoroacetic acid]]

* [[Trichloroacetic acid]], the chlorinated analog

{{Authority control}}

[[Category:Perfluorocarboxylic acids]]

[[Category:Trifluoroacetates|*]]

[[Category:Organic compounds with 2 carbon atoms]]