Pivaloyl chloride

Chemical Properties

Colorless to yellow liquid

Uses

Widely used N-acylating agent for amines,1 Schiff bases,2 and pyrrolidinones3 as well as O-acylating agent for alcohols,4 lactones,5 and saccharides.6

Uses

Trimethylacetyl chloride is used as a precursor in the preparation of tert-butyl peroxypivalate, guttiferon A derivatives, which is potential for the treatment of malaria. It is used as a raw material in the production of synthetic acidamide medicament and phenol ester medicament. In addition to this, it is used for the synthesis of active pharmaceutical ingredients such as aminobenzylpenicilin, cephalexin, cefazolin, dipivefrin and dipivalyl epinephrine. It is also used in heavy polymerization, N-acylating agent for amines, Schiff bases, pyrrolidinones as well as an O-acylating agent for alcohols, lactones and saccharides.

Synthesis Reference(s)

Tetrahedron Letters, 29, p. 4569, 1988 DOI: 10.1016/S0040-4039(00)80549-3

General Description

Colorless fuming liquid with a pungent odor. Boiling point 105-106°F. Density 0.979 g / cm3. Flash point 48°F (8°C). Very toxic by inhalation, ingestion or skin absorption. Fumes irritate the eyes and mucous membranes. Corrosive to most metals and tissue.

Air & Water Reactions

Highly flammable. Fumes in air. Reacts vigorously and exothermically with water to form trimethylacetic acid and corrosive hydrochloric acid; both acids corrode metals and tissue [AAR 1991].

Reactivity Profile

Pivaloyl chloride is acidic. Incompatible with bases (including amines), strong oxidizing agents, and alcohols. May react vigorously or explosively if mixed with diisopropyl ether or other ethers in the presence of trace amounts of metal salts [J. Haz. Mat., 1981, 4, 291].

Health Hazard

May cause toxic effects if inhaled or ingested/swallowed. Contact with substance may cause severe burns to skin and eyes. Fire will produce irritating, corrosive and/or toxic gases. Vapors may cause dizziness or suffocation. Runoff from fire control or dilution water may cause pollution.

Fire Hazard

Flammable/combustible material. May be ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapor explosion hazard indoors, outdoors or in sewers. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water.

Flammability and Explosibility

Flammable

Safety Profile

A corrosive irritant to skin, eyes, and mucous membranes. The liquid is flammable when exposed to heat, flame, or oxiduers. When heated to decomposition it emits toxic fumes of Cl-.

Purification Methods

First check the IR to see if OH bands are present. If absent, or present in small amounts, then redistil it under a moderate vacuum. If present in large amounts then treat it with oxalyl chloride or thionyl chloride and reflux for 2-3hours, evaporate and distil the residue. Strongly LACHRYMATORY -work in a fumecupboard. Store it in sealed ampoules under N2. [Traynham & Battiste J Org Chem 22 1551 1957, Grignard reactions: Whitmore et al. J Am Chem Soc 63 647 1941, Beilstein 2 IV 912.]

Toxics Screening Level

The initial threshold screening level (ITSL) for pivaloyl chloride (also known as trimethylacetyl chloride) is 8 μg/m3 with annual averaging time.