Sulphur dioxide/pyridine

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. 

A method of estimating small amounts of water in organic liquids (and also in some inorganic salts) is that of Karl Fischer. The substance is titrated with a mixture of iodine, sulphur dioxide and pyridine dissolved in methyl alcohol. The essential reaction is ... 

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 ... 

The Karl Fischer procedure has now been simplified and the accuracy improved by modification to a coulometric method (Chapter 14). In this procedure the sample under test is added to a pyridine-methanol solution containing sulphur dioxide and a soluble iodide. Upon electrolysis, iodine is liberated at the anode and reactions (a) and (b) then follow the end point is detected by a pair of electrodes which function as a biamperometric detection system and indicate the presence of free iodine. Since one mole of iodine reacts with one mole of water it follows that 1 mg of water is equivalent to 10.71 coulombs. 

Another group of Japanese workers91 found that the sulphoxonium salt, 7, was reducible to sulphoxides with either alkyllithiums or lithium dialkylcuprates, the exact reaction pathway being complicated by halide ions originating from the preparation of the metal alkyls. However, good yields of methyl phenyl sulphoxide were obtained by reduction of 7 with sulphur dioxide or a thiol in pyridine (equation 37). 

Verhoef and co-workers suggested omitting the foul smelling pyridine completely and proposed a modified reagent, consisting of a methanolic solution of sulphur dioxide (0.5 M) and sodium acetate (1M) as the solvent for the analyte, and a solution of iodine (0.1 M) in methanol as the titrant the titration proceeds much faster and the end-point can be detected preferably bipoten-tiometrically (constant current of 2 pA), but also biamperometrically (AE about 100 mV) and even visually as only a little of the yellow sulphur dioxide-iodide complex S02r is formed (for the coulometric method see Section 3.5). 

One mole of iodine will consume 2 x 96 485 coulombs of electricity. The Karl Fischer titration is widely used for the determination of water in pharmaceuticals. Quantitation in this case is not based on the total amount of current which flows through the solution but the reduction of iodine is simply used to indicate the endpoint of the titration. The reagent consists of mixture of anhydrous methanol, anhydrous pyridine, iodine and sulphur dioxide. The equation for the reaction of water with the reagent looks complicated (see below)... 

Ferrous chloride in acid solution is partially oxidised by sulphur dioxide to the ferric salt, sulphur being deposited.2 Solutions of ferrous chloride in various solvents such as water, alcohol, ethylacetate, pyridine, etc., absorb nitric oxide, the extent of absorption depending upon the concentration of the iron salt, the temperature, gaseous pressure, and the nature of the solvent. The limit of absorption is reached with one molecule of NO to one atom of iron. Presumably the compound FeCl2.NO exists in solution, most probably combined with the solvent.3 It has not as yet been isolated.4... 

Of these, water is perhaps by far the substance most determined in foods by biamperometric titration. The determination of water is perhaps worthy of a more complete coverage. The determination is based on the titrimetric procedure developed by Fischer [87] in 1935. His procedure involved the preparation of a titrating reagent consisting of a mixture of iodine, sulphur dioxide and pyridine in methanol. The titration reaction with water involves a two-stage reaction ... 

Several physical and chemical procedures have been elaborated for the determination of small amounts of water in solvents [Ha 72, Mi 61], but in most cases the Karl Fischer titrimetric method [Fi 35] has proved the most suitable. The essence of the method is that, in methanolic solution containing pyridine as proton binder, the reaction between sulphur dioxide and iodine in the presence of water takes place quantitatively in accordance with the equation... 

Accordingly, one molecule of water ensures the oxidation of one molecule of sulphur dioxide by one molecule of iodine. As the reaction is quantitative, it can be utilized for the determination of the water content of the system. If a solution containing moisture is titrated with a methanolic Karl Fischer titrant solution containing sulphur dioxide, iodine and pyridine, the iodine will be reduced in... 

The water content of polyols can be determined by the Karl Fischer method which is based on the reduction of iodine by sulphur dioxide in the presence of water. The reaction occurs quantitatively only in the presence of pyridine and methanol, which both take part in the reaction. Standard Karl Fischer reagent consisting of iodine, pyridine and sulphur dioxide in ethylene glycol monomethyl ether is available commercially and it is recommended that this be used. The polyol is mixed with anhydrous methanol and the dissolved water titrated with the Karl Fischer reagent. The colour change from yellow to brown is not easy to determine accurately and potentio-metric titrations are common. 

The application of the standard Kyodai nitration procedure for pyridine gives a mixture of 5- and 3, 5-nitropyridine in only 2-5% yield [34]. However, pyridine can be efficiently nitrated by N,0 in liquid sulphur dioxide to give 3-nitropyridine in 68% yield [35]. The role of sulphur dioxide in the process is evident from the following scheme [34] ... 

The method depends upon the reaction of the water to be determined with iodine and sulphur dioxide in pyridine-methanol solution. The pyridine prevents loss of sulphur dioxide from the reagent by forming an additive compound and also assists completion of the reaction with water by combining with the products of the reaction. The reaction between water and the reagent is complex and the stoichiometrical relationships are uncertain hence it is necessary to standardise the reagent empirically against weighed amounts of water. 

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. 

With sulphur trioxide in sulphur dioxide at —10°, pyridine, 2,6-lutidine and 2,6-di-isopropylpyridine give addition complexes (p. 162). In contrast,... 

The quaternization of pyridine in non-polar solvents has been studied as a means of clarifying the much debated nature of the displacement reaction under such circumstances . Swain and Eddy i deduced evidence for their theory of specific solvation from the reaction of pyridine and methyl bromide in benzene containing various hydroxylic solutes. Swain and Langs-dorf45ii> found the Hammett plot for the reaction of substituted benzyl bromides with pyridine in acetone to be markedly concave, and indeed to fall into two separate lines for meta- and / zm-substituents. The curvature and the division illustrate the effects of substituents upon reactions of intermediate character. Ingold and his co-workers from reactions in sulphur dioxide,... 

Acetyl- 8 benzoyl- " 489-90 nd various other acylpyridinium chlorides 86-8, 491-3 sometimes of doubtful purity (because of their very ready hydrolysis or of contamination with pyridinium chloride), have been described. Salts of benzoylpyridinium with complex metal anions are also known 94. Covalent structures, with the chlorine atom at C(2) or C(4) of the pyridine ring, have been suggested for the adducts from pyridine and the nitrobenzoyl chlorides , but the ionic character of 1-acetylpyridinium chloride is affirmed by measurements of its electrical conductivity in sulphur dioxide solution . 

The reaction using picolinic acid is catalysed by sulphur dioxide the effect may be produced either because ionization of the thionyl chloride is assisted or because of complexing of the sulphur dioxide with the pyridine nitrogen atom. ... 

Pyridine-2- and -4-sulphonyl chlorides are unstable compounds, which are said to decompose above 0° to give sulphur dioxide and the chloropyridines . Pyridine-3-sulphonyl chloride is stable as its hydrochloride . All three isomers readily give amides. 

Pyridine-3-sulphonyl chloride is reduced to the thiol by stannous chloride s and to the disulphide by sulphur dioxide and hydriodic acid s . With hydrazine hydrate in diethylene glycol, the pyridinesulphonyl chlorides give the disulphides S 2, and with zinc and water, pyridine-2-sulphonyl chlorides yield the sulphinic acids s ... 

Occasionally the curve of equivalent conductivity against concentration is found to pass through a minimum value. This behaviour is common for salts in pyridine, sulphur dioxide and the aliphatic amines, all solvents with dielectric constants around 10. It also occurs in aqueous solutions of lanthanum ferricyanide and of the colloidal electrolytes. 

Mix together in a 250 ml. flask carrying a reflux condenser and a calcium chloride drying tube 25 g. (32 ml.) of freshly-distilled acetaldehyde with a solution of 59-5 g. of dry, powdered malonic acid (Section 111,157) in 67 g. (68-5 ml.) of dry pyridine to which 0-5 ml. of piperidine has been added. Leave in an ice chest or refrigerator for 24 hours. Warm the mixture on a steam bath until the evolution of carbon dioxide ceases. Cool in ice, add 60 ml. of 1 1 sulphuric acid (by volume) and leave in the ice bath for 3-4 hours. Collect the crude crotonic acid (ca. 27 g.) which has separated by suction filtration. Extract the mother liquor with three 25 ml. portions of ether, dry the ethereal extract, and evaporate the ether the residual crude acid weighs 6 g. Recrystallise from light petroleum, b.p. 60-80° the yield of erude crotonic acid, m.p. 72°, is 20 g. 

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