Pivalic acid explained

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)₃CCO₂HSuch 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 carbonation of the Grignard reagent formed from tert-butyl chloride and by oxidation of pinacolone.

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.

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.^{[4] [5]}

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.^[6]

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.^{[7] [8] [9] [10]}

See also

• Methyl pivalate

Notes and References

1. Book: 10.1002/14356007.a05_235.pub2 . Carboxylic Acids, Aliphatic . Ullmann's Encyclopedia of Industrial Chemistry . 2014 . Kubitschke . Jens . Lange . Horst . Strutz . Heinz . 1–18 . 9783527306732 .
2. 10.1002/cber.18730060154 . A. Henninger, aus Paris 10. Februar 1873 . Berichte der Deutschen Chemischen Gesellschaft . 1873 . 6 . 144–147 .
3. Butlerow, Ann. 165, 322 (1873).
4. 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. 10.1021/ja067144j. 0002-7863. 17177387.
5. 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. 10.1002/chem.200802001. 19115287 . 0947-6539. free.
6. 10.1021/jo01322a026 . 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 . The Journal of Organic Chemistry . 44 . 8 . 1317–22 . 1979 . Robins . Morris J. . Hawrelak . S. D. . Kanai . Tadashi . Siefert . Jan Marcus . Mengel . Rudolf.
7. 10.1016/S0040-4039(01)95462-0 . Synthesis of glucosylphosphatidylglycerol via a phosphotriester intermediate . Tetrahedron Letters . 20 . 37 . 3561–4 . 1979 . Van Boeckel . C.A.A. . Van Boom . J.H..
8. 10.1016/0040-4020(68)88015-9 . 5637486 . The Synthesis of oligoribonucleotides—IV . Tetrahedron . 24 . 2 . 639–62 . 1968 . Griffin . B.E. . Jarman . M. . Reese . C.B..
9. 10.1016/S0040-4039(01)95650-3 . Use of the tert-butyldimethylsilyl group for protecting the hydroxyl functions of nucleosides . Tetrahedron Letters . 14 . 4 . 317–9 . 1973 . Ogilvie . Kelvin K. . Iwacha . Donald J..
10. 10.1021/ja974010k . . 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 . 1998 . Paquette . Leo A. . Collado . Iván . Purdie . Mark.