Chlorobutanol Chemical Properties

Melting point:

~78 °C

Boiling point:

173 °C

Density 

1.3170 (estimate)

Flash point:

>110°C

storage temp. 

Sealed in dry,Room Temperature

solubility 

Slightly soluble in water, very soluble in ethanol (96 per cent), soluble in glycerol (85 per cent).

pka

12.87±0.29(Predicted)

form 

Solid

color 

Hydrated crystals

Odor

camphor odor

Water Solubility 

8g/L(20 ºC)

Stability:

Stable. Generates toxic fumes on combustion.

LogP

2.030

CAS DataBase Reference

57-15-8(CAS DataBase Reference)

NIST Chemistry Reference

2-(Trichloromethyl)-2-propanol(57-15-8)

EPA Substance Registry System

1,1,1-Trichloro-2-methyl-2-propanol (57-15-8)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22-36/37/38

Safety Statements 

26-36/37/39

WGK Germany 

3

Hazardous Substances Data

57-15-8(Hazardous Substances Data)

Toxicity

MLD orally in dogs, rabbits (mg/kg): 238, 213 (Impens)

MSDS

• Language:English Provider:SigmaAldrich
• Language:English Provider:ALFA

Chlorobutanol Usage And Synthesis

Chemical Properties

White or almost white, crystalline powder or colourless crystals, sublimes readily

Chemical Properties

Volatile, colorless or white crystals with a musty, camphoraceous odor.

Originator

Chlorobutanol,Narchem

Uses

Chlorobutanol is used as a preservative and sedative. It has also been shown to exhibit antibacterial properties.

Uses

Plasticizer for cellulose esters and ethers, preservative for biological fluids and solutions, antimicrobial agent, anesthetic in dentistry.

Production Methods

Chlorobutanol is prepared by condensing acetone and chloroform in the presence of solid potassium hydroxide.

Definition

ChEBI: Chlorobutanol is a tertiary alcohol.

Manufacturing Process

33 g (0.59 mol) of powdered potassium hydroxide was added in small amounts to a solution of 50 g (0.86 mol) of acetone in 100 g (0.84 mol) of chloroform to form a reaction mixture containing approximately 0.7 mol of KOH per mol of chloroform. The mixture was chilled to a temperature below 0°C, thoroughly agitated, and than allowed to stand at temperature of about 0°C for 24 hours. The mixture was then filtered and the filtrate was distilled. The fraction boiling within the range of 165-175°C was poured into an equal amount of water to precipitate the 1,1,1-trichloro-tert-butyl alcohol. The precipitated 1,1,1-trichloro-tert-butyl alcohol was filtered and recrystallized from an ethanol-water mixture and air dried. The yield of 1,1,1-trichloro-tertbutyl alcohol was 6 g, that is, somewhat less than 4% of the theoretical yield based on chloroform charged. When calculated on the basis of chloroform consumed the yield was about 15%.

Therapeutic Function

Hypnotic, Anesthetic, Antiseptic, Pharmaceutic aid, Ophthalmologic

Synthesis Reference(s)

Journal of the American Chemical Society, 70, p. 1189, 1948 DOI: 10.1021/ja01183a092

Hazard

Action similar to chloral hydrate. Combustible.

Pharmaceutical Applications

Chlorobutanol is primarily used in ophthalmic or parenteral dosage forms as an antimicrobial preservative at concentrations up to 0.5% w/v. It is commonly used as an antibacterial agent for epinephrine solutions, posterior pituitary extract solutions, and ophthalmic preparations intended for the treatment of miosis. It is especially useful as an antibacterial agent in nonaqueous formulations. Chlorobutanol is also used as a preservative in cosmetics ; as a plasticizer for cellulose esters and ethers; and has been used therapeutically as a mild sedative and local analgesic in dentistry.

Safety Profile

Poison by ingestion. A narcotic. A skin and eye irritant. Mutation data reported. See also CHLORAL HYDRATE, whch acts similarly. Dangerous; can react with oxidizing materials. Combustible when exposed to heat or flame. When heated to decomposition it emits toxic fumes of Cl-. See also PHOSGENE.

Safety

Chlorobutanol is widely used as a preservative in a number of pharmaceutical formulations, particularly ophthalmic preparations. Although animal studies have suggested that chlorobutanol may be harmful to the eye, in practice the widespread use of chlorobutanol as a preservative in ophthalmic preparations has been associated with few reports of adverse reactions. A study of the irritation potential of a local anesthetic on the murine cornea indicated significant corneal surface damage in the presence of 0.5% w/v chlorobutanol, which may be related to the preservative’s effective concentration. Reported adverse reactions to chlorobutanol include: cardiovascular effects following intravenous administration of heparin sodium injection preserved with chlorobutanol; neurological effects following administration of a large dose of morphine infusion preserved with chlorobutanol; and hypersensitivity reactions, although these are regarded as rare.
The lethal human dose of chlorobutanol is estimated to be 50–500 mg/kg.
LD₅₀ (dog, oral): 0.24 g/kg
LD₅₀ (mouse, oral): 0.99 g/kg
LD₅₀ (rabbit, oral): 0.21 g/kg

storage

Chlorobutanol is volatile and readily sublimes. In aqueous solution, degradation to carbon monoxide, acetone and chloride ion is catalyzed by hydroxide ions. Stability is good at pH 3 but becomes progressively worse with increasing pH. The half-life at pH 7.5 for a chlorobutanol solution stored at 258℃ was determined to be approximately 3 months. In a 0.5% w/v aqueous chlorobutanol solution at room temperature, chlorobutanol is almost saturated and may crystallize out of solution if the temperature is reduced.
Losses of chlorobutanol also occur owing to its volatility, with appreciable amounts being lost during autoclaving; at pH 5 about 30% of chlorobutanol is lost. Porous containers result in losses from solutions, and polyethylene containers result in rapid loss. Losses of chlorobutanol during autoclaving in polyethylene containers may be reduced by pre-autoclaving the containers in a solution of chlorobutanol; the containers should then be used immediately. There is also appreciable loss of chlorobutanol through stoppers in parenteral vials.
The bulk material should be stored in an airtight container at a temperature of 8–158℃.

Incompatibilities

Owing to problems associated with sorption, chlorobutanol is incompatible with plastic vials, rubber stoppers, bentonite, magnesium trisilicate, polyethylene, and polyhydroxyethylmethacrylate, which has been used in soft contact lenses. To a lesser extent, carboxymethylcellulose and polysorbate 80 reduce antimicrobial activity by sorption or complex formation.

Regulatory Status

Included in the FDA Inactive Ingredients Database (IM, IV, and SC injection; inhalations; nasal, otic, ophthalmic, and topical preparations). Labeling must state ‘contains chlorobutanol up to 0.5%.’ Included in nonparenteral and parenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.
In the UK, the maximum concentration of chlorobutanol permitted for use in cosmetics, other than foams, is 0.5%. It is not suitable for use in aerosols.

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