pivalic acid
{{chembox
| Watchedfields = changed
| verifiedrevid = 477511917
| ImageFileL1 = Pivalic acid.svg
| ImageFileR1 = Pivalic-acid-3D-balls.png
| PIN = 2,2-Dimethylpropanoic acid
| OtherNames = Pivalic acid
Dimethylpropanoic acid
Neopentanoic acid
Neovaleric acid
Trimethylacetic acid
| Section1 = {{Chembox Identifiers
|CASNo =75-98-9
|CASNo_Ref = {{cascite|correct|CAS}}
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = 813RE8BX41
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 322719
|PubChem = 6417
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID = 6177
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI = 45133
|SMILES = O=C(O)C(C)(C)C
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C5H10O2/c1-5(2,3)4(6)7/h1-3H3,(H,6,7)
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = IUGYQRQAERSCNH-UHFFFAOYSA-N
}}
| Section2 = {{Chembox Properties
|C=5
|H=10
|O=2
|Density = 0.905 g/cm3
|MeltingPtC = 35
|BoilingPtC = 163.7
|pKa = 5.03
}}
| Section4 = {{Chembox Related
|OtherFunction_label = alcohols
|OtherCompounds = neopentyl alcohol
neopentane
Pivalamide
Pivaldehyde
}}
}}
Pivalic acid is a carboxylic acid with a molecular formula of (CH3)3CCO2H. This colourless, odiferous organic compound is solid at room temperature. Two abbreviations for pivalic acid are t-BuC(O)OH and PivOH. The pivalyl or pivaloyl group is abbreviated t-BuC(O).
Pivalic acid is an isomer of valeric acid, the other two isomers of it are 2-Methylbutanoic acid and 3-Methylbutanoic acid.
Preparation
Pivalic acid is prepared on a commercial scale by hydrocarboxylation of isobutene via the Koch reaction:
:(CH3)2C=CH2 + CO + H2O → (CH3)3CCO2H
Such reactions require an acid catalyst such as hydrogen fluoride. tert-Butyl alcohol and isobutyl alcohol can also be used in place of isobutene. Globally, several million kilograms are produced annually.{{cite book |doi=10.1002/14356007.a05_235.pub2 |chapter=Carboxylic Acids, Aliphatic |title=Ullmann's Encyclopedia of Industrial Chemistry |date=2014 |last1=Kubitschke |first1=Jens |last2=Lange |first2=Horst |last3=Strutz |first3=Heinz |pages=1–18 |isbn=9783527306732 }} Pivalic acid is also economically recovered as a byproduct from the production of semisynthetic penicillins like ampicillin and amoxycillin.
It was originally prepared by the oxidation of pinacolone with chromic acid.{{cite journal|doi=10.1002/cber.18730060154 |title=A. Henninger, aus Paris 10. Februar 1873 |journal=Berichte der Deutschen Chemischen Gesellschaft |date=1873 |volume=6 |pages=144–147 }} Alternative oxidative route uses aqueous bromine.and by oxidation of pinacolone.{{OrgSynth |title= Trimethylacetic acid from Pinacolone |author1=S. V. Puntambeker |author2=E. W. Zoellner |volume= 8 |page= 104 |year= 1928 |doi=10.15227/orgsyn.008.0104}}
:File:Acetone2pinacolone (cropped).svg
The hydrolysis of tert-butyl cyanide has also been described.Butlerow, Ann. 165, 322 (1873).{{full citation needed|date=June 2017}} Another laboratory route involves carbonation of the Grignard reagent formed from tert-butyl chloride{{OrgSynth |title= Trimethylacetic acid from tert-Butyl Chloride |author1= S. V. Puntambeker |author2=E. A. Zoellner |author3=L. T. Sandborn |author4=E. W. Bousquet |collvol= 1 |collvolpages= 524 |year= 1941 |prep= cv1p0524 |doi=10.15227/orgsyn.008.0104}}
Applications
Relative to esters of most carboxylic acids, esters of pivalic acid are unusually resistant to hydrolysis. Some applications result from this thermal stability. Polymers derived from pivalate esters of vinyl alcohol are highly reflective lacquers.{{cn|date=October 2023}}
Use in the laboratory
Pivalic acid is sometimes used as an internal chemical shift standard for NMR spectra of aqueous solutions. While DSS is more commonly used for this purpose, the minor peaks from protons on the three methylene bridges in DSS can be problematic. The 1H NMR spectrum at 25 °C and neutral pH is a singlet at 1.08 ppm.{{cn|date=January 2025}}
Pivalic acid is employed as co-catalyst in some palladium-catalyzed C-H functionalization reactions.{{Cite journal|last1=Lafrance|first1=Marc|last2=Fagnou|first2=Keith|date=2006-12-27|title=Palladium-catalyzed benzene arylation: incorporation of catalytic pivalic acid as a proton shuttle and a key element in catalyst design|url=https://www.ncbi.nlm.nih.gov/pubmed/17177387|journal=Journal of the American Chemical Society|volume=128|issue=51|pages=16496–16497|doi=10.1021/ja067144j|issn=0002-7863|pmid=17177387}}{{Cite journal|last1=Zhao|first1=Dongbing|last2=Wang|first2=Weida|last3=Lian|first3=Shuang|last4=Yang|first4=Fei|last5=Lan|first5=Jingbo|last6=You|first6=Jingsong|date=2009-01-26|title=Phosphine-Free, Palladium-Catalyzed Arylation of Heterocycles through C-H Bond Activation with Pivalic Acid as a Cocatalyst|url=https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.200802001|journal=Chemistry – A European Journal|volume=15|issue=6|pages=1337–1340|doi=10.1002/chem.200802001|pmid=19115287 |issn=0947-6539|doi-access=free}}
=Alcohol protection=
The pivaloyl (abbreviated Piv or Pv) group is a protective group for alcohols in organic synthesis. Common protection methods include treatment of alcohol with pivaloyl chloride (PvCl) in presence of pyridine.{{cite journal |doi=10.1021/jo01322a026 |title=Nucleic acid related compounds. 30. Transformations of adenosine to the first 2',3'-aziridine-fused nucleosides, 9-(2,3-epimino-2,3-dideoxy-.beta.-D-ribofuranosyl)adenine and 9-(2,3-epimino-2,3-dideoxy-.beta.-D-lyxofuranosyl)adenine |journal=The Journal of Organic Chemistry |volume=44 |issue=8 |pages=1317–22 |year=1979 |last1=Robins |first1=Morris J. |last2=Hawrelak |first2=S. D. |last3=Kanai |first3=Tadashi |last4=Siefert |first4=Jan Marcus |last5=Mengel |first5=Rudolf}}
Alternatively, the esters can be prepared using pivaloic anhydride in the presence of Lewis acids such as scandium triflate (Sc(OTf)3).
Common deprotection methods involve hydrolysis with a base or other nucleophiles.{{cite journal |doi=10.1016/S0040-4039(01)95462-0 |title=Synthesis of glucosylphosphatidylglycerol via a phosphotriester intermediate |journal=Tetrahedron Letters |volume=20 |issue=37 |pages=3561–4 |year=1979 |last1=Van Boeckel |first1=C.A.A. |last2=Van Boom |first2=J.H.}}{{cite journal |doi=10.1016/0040-4020(68)88015-9 |pmid=5637486 |title=The Synthesis of oligoribonucleotides—IV |journal=Tetrahedron |volume=24 |issue=2 |pages=639–62 |year=1968 |last1=Griffin |first1=B.E. |last2=Jarman |first2=M. |last3=Reese |first3=C.B.}}{{cite journal |doi=10.1016/S0040-4039(01)95650-3 |title=Use of the tert-butyldimethylsilyl group for protecting the hydroxyl functions of nucleosides |journal=Tetrahedron Letters |volume=14 |issue=4 |pages=317–9 |year=1973 |last1=Ogilvie |first1=Kelvin K. |last2=Iwacha |first2=Donald J.}}{{cite journal |doi=10.1021/ja974010k |id={{INIST|10388970}}|title=Total Synthesis of Spinosyn A. 2. Degradation Studies Involving the Pure Factor and Its Complete Reconstitution |journal=Journal of the American Chemical Society |volume=120 |issue=11 |pages=2553–62 |year=1998 |last1=Paquette |first1=Leo A. |last2=Collado |first2=Iván |last3=Purdie |first3=Mark}}
