Karl Fischer reagent preparation

The original Karl Fischer reagent prepared with an excess of methanol was somewhat unstable and required frequent standardisation. It was found that the stability was improved by replacing the methanol by 2-methoxyethanol. 

Commercially available Karl Fischer reagent is stabilized and can be obtained free of pyridine, which is toxic. It can also be prepared in the laboratory however, this requires the use ofS02, a poisonous, liquified gas. 

Standardization of Water Solution for Residual Titration Prepare a Water Solution by diluting 2 mL of pure water to 1000 mL with methanol or another suitable solvent. Standardize this solution by titrating 25.0 mL with the Karl Fischer Reagent, previously standardized as directed under Standardization of the Reagent. Calculate the water content, in milligrams per milliliter, of the Water Solution with the formula... 

Procedure Where the individual monograph specifies the water content is to be determined by Method lb, transfer 35 to 40 mL of methanol or other suitable solvent into the titration vessel, and titrate with the Karl Fischer Reagent to the electrometric or visual endpoint. Quickly add the Test Preparation, mix, and add an accurately measured excess of the Karl Fischer Reagent. Allow sufficient time for the reaction to reach completion, and titrate the unconsumed Karl Fischer Reagent with standardized Water Solution to the electrometric or visual endpoint. Calculate the water content of the specimen, in milligrams, with the formula... 

Karl Fischer reagent decomposes on standing. Because decomposition is particularly rapid immediately after preparation, it is common practice to prepare the reagent a day or two before it is to be used. Ordinarily, its strength must be established at least daily against a standard solution of water in methanol. A proprietary commercial Karl Fischer reagent reported to require only occasional restandardization is now available. 

Karl Fischer reagent. Dissolve 63 g of analytical-reagent grade iodine in 110 ml of dehydrated pyridine in a dry gas wash-bottle (of which the delivery tube is fitted with a screw-clip and the exit tube connected to an efficient drying tube) and weigh the bottle and its contents. Cool in ice-water and pass dry sulphur dioxide into the cold solution, stirring continuously, until the increase in weight is 32 g. Allow the mixture to stand for about thirty minutes and then dilute to 500 ml with dry methanol. When freshly prepared the solution will have a water equivalent of about 5 mg per ml but slowly decomposes. It should be allowed to stand for tw enty-four hours before standardisation. 

For the determination of small amounts of water, Karl Fischer (1935) proposed a reagent prepared by the action of sulphur dioxide upon a solution of iodine in a mixture of anhydrous pyridine and anhydrous methanol. Water reacts with this reagent in a two-stage process in which one molecule of iodine disappears for each molecule of water present ... 

All enthalpy of solution measurements were carried out with an LKB 8700-1 precision calorimetry system. The experimental procedure and tests of the calorimeter have been reported previously (3, 4, 5). The purification of the solvent DMF (Baker Analyzed Reagent) and of all solutes used has been described in the same papers. The solvent mixtures were prepared by weighing and the mole fraction of water in the DMF-water mixtures was corrected for the original water content of the amide as measured by Karl Fischer titration. 

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