Pivalic acid

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Pivalic acid
Pivalic acid.svg
Pivalic-acid-3D-balls.png
Names
Preferred IUPAC name
2,2-Dimethylpropanoic acid
Other names
Pivalic acid
Dimethylpropanoic acid
Neopentanoic acid
Neovaleric acid
Trimethylacetic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.839 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C5H10O2/c1-5(2,3)4(6)7/h1-3H3,(H,6,7) Yes check.svgY
    Key: IUGYQRQAERSCNH-UHFFFAOYSA-N Yes check.svgY
  • O=C(O)C(C)(C)C
Properties
C5H10O2
Molar mass 102.133 g·mol−1
Density 0.905 g/cm3
Melting point 35 °C (95 °F; 308 K)
Boiling point 163.7 °C (326.7 °F; 436.8 K)
Related compounds
Related compounds
neopentyl alcohol
neopentane
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

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).

Contents

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. [1] 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 [2] and by the hydrolysis of tert-butyl cyanide. [3] Convenient laboratory routes proceed via tert-butyl chloride via carbonation of the Grignard reagent [4] and by oxidation of pinacolone. [5]

Pinacol rearrangement Acetone2pinacolone.svg
Pinacol rearrangement
t-Butylmagnesium bromide reacts with CO2 to form the pivalate salt. Addition of acid yields pivalic acid Carboxylation of alkyl magnesium halides.svg
t-Butylmagnesium bromide reacts with CO2 to form the pivalate salt. Addition of acid yields pivalic acid

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.[ citation needed ]

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.

Pivalic acid is employed as co-catalyst in some palladium-catalyzed C-H functionalization reactions. [6] [7]

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. [8]

PvProtectedAlcohol.png

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. [9] [10] [11] [12]

PvProtection.png

See also

Related Research Articles

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<span class="mw-page-title-main">Ester</span> Compound derived from an acid

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References

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  2. "A. Henninger, aus Paris 10. Februar 1873". Berichte der Deutschen Chemischen Gesellschaft. 6: 144–147. 1873. doi:10.1002/cber.18730060154.
  3. Butlerow, Ann. 165, 322 (1873).[ full citation needed ]
  4. S. V. Puntambeker; E. A. Zoellner; L. T. Sandborn; E. W. Bousquet (1941). "Trimethylacetic acid from tert.- Butyl Chloride". Organic Syntheses . doi:10.15227/orgsyn.008.0104 ; Collected Volumes, vol. 1, p. 524.
  5. L. T. Sandborn; E. W. Bousquet (1941). "Trimethylacetic acid from Pinacolone". Organic Syntheses . doi:10.15227/orgsyn.008.0104 ; Collected Volumes, vol. 1, p. 524.
  6. Lafrance, Marc; Fagnou, Keith (2006-12-27). "Palladium-catalyzed benzene arylation: incorporation of catalytic pivalic acid as a proton shuttle and a key element in catalyst design". Journal of the American Chemical Society. 128 (51): 16496–16497. doi:10.1021/ja067144j. ISSN   0002-7863. PMID   17177387.
  7. Zhao, Dongbing; Wang, Weida; Lian, Shuang; Yang, Fei; Lan, Jingbo; You, Jingsong (2009-01-26). "Phosphine-Free, Palladium-Catalyzed Arylation of Heterocycles through C-H Bond Activation with Pivalic Acid as a Cocatalyst". Chemistry – A European Journal. 15 (6): 1337–1340. doi: 10.1002/chem.200802001 . ISSN   0947-6539. PMID   19115287.
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  11. Ogilvie, Kelvin K.; Iwacha, Donald J. (1973). "Use of the tert-butyldimethylsilyl group for protecting the hydroxyl functions of nucleosides". Tetrahedron Letters. 14 (4): 317–9. doi:10.1016/S0040-4039(01)95650-3.
  12. Paquette, Leo A.; Collado, Iván; Purdie, Mark (1998). "Total Synthesis of Spinosyn A. 2. Degradation Studies Involving the Pure Factor and Its Complete Reconstitution". Journal of the American Chemical Society. 120 (11): 2553–62. doi:10.1021/ja974010k. INIST   10388970.