Chlorbutol

Chlorbutol or Chlorobutanol has preservative as well as antibacterial and antifungal activity. Apart from other uses, it is used for treatment of impacted ear wax. As a long-term stabilizer of multi-ingredient preparations, chlorobutanol is normally used at a concentration of 0.5%. At this concentration, it also conserves its antimicrobial activity. It is used as is a preservative, sedative, hypnotic and weak local anesthetic.

Properties and General Specifications of Chlorbutol or Chlorobutanol or 1,1,1-Trichloro-2-methyl-2-propanol:
Appearance: Colorless to white crystals.
Assay: 99% minimum.
Odor: Camphor like odor.
Taste: Camphor like taste.
Melting point: 97 to 99C literature.
Boiling point: 167C literature.
Solubility: Soluble in water. Soluble in alcohol and glycerol, ether, chloroform.

Specifications of Chlorobutanol USP NF Grade:
C4H7Cl3O (anhydrous) --- 177.46
2-Propanol, 1,1,1-trichloro-2-methyl-.
1,1,1-Trichloro-2-methyl-2-propanol --- 57-15-8.
Hemihydrate --- 186.46 --- CAS 6001-64-5.

Chlorobutanol is anhydrous or contains not more than one-half molecule of water of hydration. It contains not less than 98.0 percent and not more than 100.5 percent of C4H7Cl3O, calculated on the anhydrous basis.
Packaging and storage: Preserve in tight containers.
Labeling: Label it to indicate whether it is anhydrous or hydrous.

Identification:
A: Infrared Absorption.
B: To 5 mL of a freshly prepared solution (1 in 200) add 1 mL of 1 N sodium hydroxide, then slowly add 3 mL of iodine: a yellow precipitate of iodoform, recognizable by its odor, appears.
Reaction: Shake thoroughly 0.5 g with 25 mL of water: the water remains neutral to litmus.
Water: not more than 1.0% (anhydrous form) and not more than 6.0% (hydrous form).
Chloride: To a solution of 0.50 g in a mixture of 25 mL of diluted alcohol and 1 mL of nitric acid add 2 mL of silver nitrate: any turbidity produced is not greater than that produced from a control solution containing 0.50 mL of 0.020 N hydrochloric acid in place of the Chlorobutanol (0.07%).
Assay:
Denatured alcohol: Dilute 100 mL of isopropyl alcohol to 1000 mL with alcohol.
Potassium hydroxide solution: Transfer 58 g of potassium hydroxide to a 1000-mL volumetric flask. Add 100 mL of water to dissolve, then cool the solution. Dilute with Denatured alcohol to volume, and mix. Prepare fresh just prior to use.
Procedure: Transfer about 100 mg of Chlorobutanol, accurately weighed, to a glass-stoppered, flat-bottomed boiling flask. Add 50 mL of Potassium hydroxide solution, attach the flask to a reflux condenser, and reflux for 1 hour. Allow the flask to cool while still attached to the condenser, then add 100 mL of water, using a portion of the water to rinse the condenser and its tip. Add 15 mL of nitric acid while stirring. Titrate with 0.1 N silver nitrate, determining the endpoint potentiometrically, using a silver-billet combination electrode, consisting of a metallic silver indicator electrode and a double junction reference electrode that allows use of a nonchloride filling solution (such as ammonium nitrate solution) for determining chloride, or equivalent. Perform a blank determination and make any necessary correction. Each mL of 0.1 N silver nitrate is equivalent to 5.915 mg of C4H7Cl3O.

Chlorobutanol Hemihydrate C4H7Cl3O-1/2H2O, CAS 6001-64-5 is generally prefered by the users

Chlorobutanol Hemihydrate BP Ph Eur Grade Specifications
C4H7Cl3O,½H2O --- 186.5 --- CAS 6001-64-5
Action and use: Disinfectant preservative.

DEFINITION
1,1,1-Trichloro-2-methylpropan-2-ol hemihydrate.
Content: 98.0 per cent to 101.0 per cent (anhydrous substance).

CHARACTERS
Appearance: White or almost white, crystalline powder or colourless crystals, sublimes readily.
Solubility: Slightly soluble in water, very soluble in ethanol (96 per cent), soluble in glycerol (85 per cent).
Melting point: About 78C (without previous drying).

IDENTIFICATION
A. Add about 20 mg to a mixture of 1 mL of pyridine and 2 mL of strong sodium hydroxide solution. Heat in a water-bath and shake. Allow to stand. The pyridine layer becomes red.
B. Add about 20 mg to 5 mL of ammoniacal silver nitrate solution and warm slightly. A black precipitate is formed.
C. To about 20 mg add 3 mL of 1 M sodium hydroxide and shake to dissolve. Add 5 mL of water and then, slowly, 2 mL of iodinated potassium iodide solution. A yellowish precipitate is formed.
D. Water (see Tests).

TESTS
Solution S: Dissolve 5 g in ethanol (96 per cent) and dilute to 10 mL with the same solvent.
Appearance of solution: Solution S is not more opalescent than reference suspension and not more intensely coloured than reference solution.
Acidity: To 4 mL of solution S add 15 mL of ethanol (96 per cent) and 0.1 mL of bromothymol blue solution. Not more than 1.0 mL of 0.01 M sodium hydroxide is required to change the colour of the indicator to blue.
Chlorides: Maximum 100 ppm.
Water: 4.5 per cent to 5.5 per cent, determined on 0.300 g.
Sulfated ash: Maximum 0.1 per cent, determined on 1.0 g.

ASSAY
Dissolve 0.100 g in 20 mL of ethanol (96 per cent). Add 10 mL of dilute sodium hydroxide solution, heat in a water-bath for 5 min and cool. Add 20 mL of dilute nitric acid, 25.0 mL of 0.1 M silver nitrate and 2 mL of dibutyl phthalate and shake vigorously. Add 2 mL of ferric ammonium sulfate solution and titrate with 0.1 M ammonium thiocyanate until an orange colour is obtained. 1 mL of 0.1 M silver nitrate is equivalent to 5.92 mg of C4H7Cl3O.

STORAGE
In an airtight container.

Chlorobutanol Hemihydrate EP is also manufactured.

Certifications :
We manufacture Bulk Drugs / API, Excipients, Pharmaceuticals (IP/BP/USP/NF/Ph. Eur, JP/ CP), Speciality Chemicals(Pure/AR/ACS), Mineral Fortifiers, Food Chemical Codex (FCC) and Flavour chemicals. Our manufacturing facility is cGMP, GLP, ISO 9001, ISO 14001, ISO 22000, ISO/IEC 17025, FSSC 22000, FSSAI, Kosher, HALAL, EXCiPACT, WC, COPP, WHO-GMP and WC certified. We are also REACH registered for export to European countries.