Pivalic acid is a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

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

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

is solid at room temperature. A common abbreviation for the pivalyl or pivaloyl group (''t''-BuC(O)) is Piv and for pivalic acid (''t''-BuC(O)OH) is PivOH.

Preparation

Industrial route

Pivalic acid is prepared by

hydrocarboxylation Carbonylation refers to reactions that introduce carbon monoxide into organic and inorganic substrates. Carbon monoxide is abundantly available and conveniently reactive, so it is widely used as a reactant in industrial chemistry. The term carbon ...

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 process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

such as

hydrogen fluoride Hydrogen fluoride (fluorane) is an inorganic compound with the chemical formula . This colorless gas or liquid is the principal industrial source of fluorine, often as an aqueous solution called hydrofluoric acid. It is an important feedstock i ...

. ''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 dire ...

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 and amoxycillin.

Laboratory methods

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 and has a slight peppermint- or camphor- odor. It is a precursor to triazolylpinacolone in the synthesis of the fungicide triadimefon and ...

with

chromic acid The term chromic acid is usually used for a mixture made by adding concentrated sulfuric acid to a dichromate, which may contain a variety of compounds, including solid chromium trioxide. This kind of chromic acid may be used as a cleaning mixtu ...

and by the hydrolysis of ''tert''-butyl cyanide. Convenient laboratory routes proceed via ''tert''-butyl chloride via carbonation of the

Grignard reagent A Grignard reagent or Grignard compound is a chemical compound 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 bromide ...

and by oxidation of pinacolone. : Acetone2pinacolone

Carboxylation of alkyl magnesium halides

Applications

Relative to esters of most carboxylic acids,

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

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), is the simplest enol. With the formula , it is a labile compound that converts to acetaldehyde. It is not a precursor to polyvinyl alcohol. Synthesis Vinyl alcohol can be formed by th ...

are highly reflective lacquers. 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 many ...

for

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

s in

organic synthesis Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...

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

NMR Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with ...

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 of the Palladium catalyzed C-H functionalization reaction.

Alcohol protection

The pivaloyl group is used as a

protecting 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 many ...

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

pyridine Pyridine is a basic 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, weakly alkaline, water-miscible liquid with a d ...

Alternatively, the esters can be prepared using pivaloic anhydride in the presence of

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

(Sc(OTf)₃) or

vanadyl triflate The vanadyl or oxovanadium(IV) cation, VO2+, is a functional group that is common in the coordination chemistry of vanadium. Complexes containing this functional group are characteristically blue and paramagnetic. A triple bond is proposed to ...

(VO(OTf)₂). Common deprotection methods involve hydrolysis with a base or other nucleophiles. PvProtection

References