Pivalic acid is a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

with a molecular formula of (CH₃)₃CCO₂H. This colourless, odoriferous

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

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 In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

valeric acid Valeric acid or pentanoic acid is a straight-chain alkyl carboxylic acid with the chemical formula . Like other low-molecular-weight carboxylic acids, it has an unpleasant odor. It is found in the perennial flowering plant '' Valeriana offici ...

, the other two isomers of it are

2-methylbutanoic acid 2-Methylbutanoic acid, also known as 2-methylbutyric acid is a branched-chain alkyl carboxylic acid with the chemical formula CH3CH2CH(CH3)CO2H, classified as a short-chain fatty acid. It exists in two enantiomeric forms, (''R'')- and (''S'')-2-m ...

and

3-methylbutanoic acid Isovaleric acid, also known as 3-methylbutanoic acid or β-methylbutyric acid, is a branched-chain alkyl carboxylic acid with the chemical formula (CH3)2CHCH2CO2H. It is classified as a short-chain fatty acid. Like other low-molecular-weight car ...

Preparation

Pivalic acid is prepared on a commercial scale by

hydrocarboxylation In chemistry, carbonylation refers to reactions that introduce carbon monoxide (CO) into organic and inorganic substrates. Carbon monoxide is abundantly available and conveniently reactive, so it is widely used as a reactant in industrial chemis ...

isobutene Isobutylene (or 2-methylpropene) is a hydrocarbon with the chemical formula . It is a four-carbon branched alkene (olefin), one of the four isomers of butylene. It is a colorless flammable gas, and is of considerable industrial value. Productio ...

via the Koch reaction: :(CH₃)₂C=CH₂ + CO + H₂O → (CH₃)₃CCO₂H Such reactions require an acid

catalyst Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

such as

hydrogen fluoride Hydrogen fluoride (fluorane) is an Inorganic chemistry, inorganic compound with chemical formula . It is a very poisonous, colorless gas or liquid that dissolves in water to yield hydrofluoric acid. It is the principal industrial source of fluori ...

. ''tert''-Butyl alcohol and

isobutyl alcohol Isobutanol (IUPAC nomenclature: 2-methylpropan-1-ol) is an organic compound with the formula (CH3)2CHCH2OH (sometimes represented as ''i''-BuOH). This colorless, flammable liquid with a characteristic smell is mainly used as a solvent either dir ...

can also be used in place of isobutene. Globally, several million kilograms are produced annually. Pivalic acid is also economically recovered as a byproduct from the production of semisynthetic penicillins like

ampicillin Ampicillin is an antibiotic belonging to the aminopenicillin class of the penicillin family. The drug is used to prevent and treat several bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, s ...

and amoxycillin. It was originally prepared by the oxidation of

pinacolone Pinacolone (3,3-dimethyl-2-butanone) is an important ketone in organic chemistry. It is a colorless liquid with a slight peppermint or camphor odor. It is a precursor to triazolylpinacolone in the synthesis of the fungicide triadimefon and in sy ...

with

chromic acid Chromic acid is a chemical compound with the chemical formula . It is also a jargon for a solution formed by the addition of sulfuric acid to aqueous solutions of dichromate. It consists at least in part of chromium trioxide. The term "chromic ...

: : An alternative oxidative route uses aqueous bromine and proceeds by oxidation of pinacolone. The hydrolysis of ''tert''-butyl cyanide has also been described. Another laboratory route involves carbonation of the

Grignard reagent Grignard reagents or Grignard compounds are chemical compounds with the general formula , where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride and phenylmagnesium bromi ...

formed from ''tert''-butyl chloride Carboxylation of alkyl magnesium halides

Applications

Relative to esters of most carboxylic acids,

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

s of pivalic acid are unusually resistant to hydrolysis. Some applications result from this thermal stability. Polymers derived from pivalate esters of

vinyl alcohol Vinyl alcohol, also called ethenol (IUPAC name; not ethanol) or ethylenol, is the simplest enol. With the formula , it is a labile compound that converts to acetaldehyde immediately upon isolation near room temperature. It is not a practical prec ...

are highly reflective lacquers.

Use in the laboratory

Pivalic acid is sometimes used as an internal chemical shift standard for

NMR Nuclear magnetic resonance (NMR) is a physical phenomenon in which atomic nucleus, nuclei in a strong constant magnetic field are disturbed by a weak oscillating magnetic field (in the near and far field, near field) and respond by producing ...

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 Palladium is a chemical element; it has symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1802 by the English chemist William Hyde Wollaston. He named it after the asteroid Pallas (formally 2 Pallas), ...

-catalyzed C-H functionalization reactions.

Alcohol protection

The pivaloyl (abbreviated Piv or Pv) group is a

protective group A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In man ...

for

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

s in

organic synthesis Organic synthesis is a branch of chemical synthesis concerned with the construction of organic compounds. Organic compounds are molecules consisting of combinations of covalently-linked hydrogen, carbon, oxygen, and nitrogen atoms. Within the gen ...

. Common protection methods include treatment of the alcohol with pivaloyl chloride (PvCl) in the presence of

pyridine Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...

Alternatively, the esters can be prepared using pivaloic anhydride in the presence of Lewis acids such as

scandium triflate Scandium trifluoromethanesulfonate, commonly called scandium triflate, is a chemical compound with formula Sc(SO3CF3)3, a salt (chemistry), salt consisting of scandium cations Sc3+ and triflate anions. Scandium triflate is used as a reagent in ...

(Sc(OTf)₃). Common deprotection methods involve hydrolysis with a base or other nucleophiles. PvProtection

References

{{Reflist Alkanoic acids Tert-butyl compounds

Preparation

Applications

Use in the laboratory

Alcohol protection

See also

References