Fischer reagent

Karl Fischer reagent A mixture ofU and SO2 dissolved in pyridine - MeOH used as a titrant for water with which HI is liberated and the pH determined with a meter. 

Another important example of a redox titration for inorganic analytes, which is important in industrial labs, is the determination of water in nonaqueous solvents. The titrant for this analysis is known as the Karl Fischer reagent and consists of a mixture of iodine, sulfur dioxide, pyridine, and methanol. The concentration of pyridine is sufficiently large so that b and SO2 are complexed with the pyridine (py) as py b and py SO2. When added to a sample containing water, b is reduced to U, and SO2 is oxidized to SO3. 

Methanol is included to prevent the further reaction of py SO3 with water. The titration s end point is signaled when the solution changes from the yellow color of the products to the brown color of the Karl Fischer reagent. 

There is no specific color or other reaction by which methyl chloride can be detected or identified. QuaUty testing of methyl chloride for appearance, water content, acidity, nonvolatile residue, residual odor, methanol, and acetone is routinely done by production laboratories. Water content is determined with Kad Fischer reagent using the apparatus by Kieselbach (55). Acidity is determined by titration with alcohoHc sodium hydroxide solution. The nonvolatile residue, consisting of oil or waxy material, is determined by evaporating a sample of the methyl chloride at room temperature. The residue is examined after evaporation for the presence of odor. Methanol and acetone content are determined by gas chromatography. 

The stability of the reagent is much improved by replacing MeOH with Me0CH2CH20H, and this forms the basis of the present-day Karl Fischer reagent. 

DETERMINATION OF WATER WITH THE KARL FISCHER REAGENT 16.35... 

The end point of the reaction is conveniently determined electrometrically using the dead-stop end point procedure. If a small e.m.f. is applied across two platinum electrodes immersed in the reaction mixture a current will flow as long as free iodine is present, to remove hydrogen and depolarise the cathode. When the last trace of iodine has reacted the current will decrease to zero or very close to zero. Conversely, the technique may be combined with a direct titration of the sample with the Karl Fischer reagent here the current in the electrode circuit suddenly increases at the first appearance of unused iodine in the solution. 

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. 

Compounds which can be regarded as forming water with the components of the Karl Fischer reagent, for example ... 

The Karl Fischer procedure was applied to the determination of water present in hydrated salts or adsorbed on the surface of solids. The procedure, where applicable, was more rapid and direct than the commonly used drying process. A sample of the finely powdered solid, containing 5-10 millimoles (90-180 mg) of water, was dissolved or suspended in 25 mL of dry methanol in a 250-mL glass-stoppered graduated flask. The mixture was titrated with standard Karl Fischer reagent to the usual electrometric end point. A blank titration was also carried out on a 25 mL sample of the methanol used to determine what correction (if any) needed to be applied to the titre obtained with the salt. 

Wash solutions for precipitates, 426 Washing of precipitates 118, 426 by decantation. 119 solubility losses in, 119, 427 Washing soda D. of sodium carbonate in, 295 Water absorbents for, 477 ammonia-free, 679 deionised, 90 D. of hardness, 332 D. of total cation concentration, 210 D. with Karl Fischer reagent 637 distilled, 90 high purity, 91 ionic product of, 36 types and standards for, (T) 90 volume of 1 g at various temperatures, (T)87... 

In a search for an accurate method of measuring moisture in foods, one cannot overlook the essential requirements of convenience, speed, and precision. Many currently used methods meet these requirements without necessarily yielding accurate results under the conditions used. Probably most important are the electrical methods (IS, 24, 26, 36), the air- and vacuum-oven methods (/, 2, 6, 18, 25, 28, 36), distillation with organic solvents (1, 3, 7, 12, 13, 26, 35), and the Karl Fischer reagent method (9, 11, 26, 31, 32). Without discussing the relative merits of these methods, it can be assumed that accurate results could be obtained with each method by calibration against some accurate reference method. 

Because of their wide applicability, emphasis is laid on the distillation methods, the Karl Fischer reagent method and particularly the vacuum-oven method. The principal assumptions are as follows ... 

It is difficult to estimate the magnitude of the error due to insufficiently low humidity when distillation methods are used with organic liquids such as toluene (6, 28), xylene (6, 28), or chloroform (12). With organic liquids essentially immiscible with water and of high boiling point the error is probably very small. When methanol is used as an extraction solvent, as in the Fischer reagent method, the amount of unextracted water is undoubtedly some function of the concentration of water in the alcohol, but the error might be small because of substitution of adsorbed water by adsorbed alcohol (23, 34). This seems to be borne out by experiments of Schroeder and Nair (31), who deliberately added water to the alcohol to form a 0.5% water solution and found that the results of their moisture determinations were essentially the same as with anhydrous methanol, which contained about 0.05% water. 

Figure 4. Moisture Determinations with Fischer Reagent as Function of Time of Soaking in Methanol at 60° C. (J J)...

Table IV. Comparison of Vacuum-Oven and Fischer Reagent Results for Dehydrated...

It is evident that the procedure to be used with the Fischer reagent can be established only in terms of some standard reference method. Schroeder and Nair (31) adopted a calibration method which involved titration with the Fischer reagent after a prolonged extraction of water from the sample in methanol at room temperature. It was assumed that the extraction at low temperature, and the avoidance of an excess of the reagent, would minimize the extent of side reactions. Two procedures were used. 

Table V. Calibration Data for Fischer Reagent Method...

Figure 10. Moisture Determinations with Fischer Reagent...

Some of the common factors that control the accuracy of these direct methods are incomplete removal of water, thermal decomposition, volatility of nonaqueous components, and certain side reactions, such as oxidation and nonspecificity of the Fischer reagent. 

Universal Titrimetric Micromethod for Determination of Water by Fischer Reagent . Inst-OrgKhimimZelinskogo 12, 2761-64 (1967)... 

A Fischer reagent had been made with pyridine, iodine, sulphur trioxide and formamide, instead of methanol. The bottle detonated after being stored for a couple of months. The authors put it down to the decomposition of formamide into ammonia and carbon oxide, which created the overpressure that caused the bottle to detonate. 

Redox titrants (mainly in acetic acid) are bromine, iodine monochloride, chlorine dioxide, iodine (for Karl Fischer reagent based on a methanolic solution of iodine and S02 with pyridine, and the alternatives, methyl-Cellosolve instead of methanol, or sodium acetate instead of pyridine (see pp. 204-205), and other oxidants, mostly compounds of metals of high valency such as potassium permanganate, chromic acid, lead(IV) or mercury(II) acetate or cerium(IV) salts reductants include sodium dithionate, pyrocatechol and oxalic acid, and compounds of metals at low valency such as iron(II) perchlorate, tin(II) chloride, vanadyl acetate, arsenic(IV) or titanium(III) chloride and chromium(II) chloride. 

Bottles containing a modified Karl Fischer reagent with formamide replacing methanol developed gas pressure during several months and burst. No reason was apparent, but slow formation of sulfuric acid, either by absorption of external water or by... 

Water IJ (Karl-Fischer reagent) amperometric organic solvents, petroleum products... 

Fischer titration cannot be used if the product reacts with iodine in the Karl Fischer reagent, or does not dissolve in methanol, or the moisture cannot be extracted by the methanol. 

In the volumetric method, the titrant can be a solution of iodine, methanol, sulfur dioxide, and an organic base, as described previously. Such a mixture is commonly known as the Karl Fischer reagent and can be purchased from any chemical vendor. It can also be a solution of iodine in methanol solvent. In that case, a Karl Fischer solvent containing the other required components is needed for the titration vessel. 

Conditioning the solvent means to eliminate all water in the solvent by titrating it with the Karl Fischer reagent. This is done to keep from measuring this water rather than the water in the sample. 

It refers to the determination of water content titrimetrically with Karl Fischer Reagent (KFR). This technique has been used exclusively for the determination of water content in a number of pharmaceutical substances listed below (see Part II G, Chapter 14) ... 

A plethora of chemical compounds for the determination of small amounts of water present in organic solids, pharmaceutical substances and organic solvents have been devised over a length of time. But unquestionably the most important of these is the one proposed by Karl Fischer (1935), which is considered to be relatively specific for water. It essentially makes use of the Karl Fischer reagent which is composed of iodine, sulphur dioxide, pyridine and methanol. 

Water present in the analyte reacts with the Karl Fischer reagent in a two-stage process as shown below ... 

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