Chloride, stannous

Stannous Chloride.—The kinetics of the insertion of SnCl2 into the M—M bond of [Co2(CO)6 P(OPh)3 a] have been studied over the temperature range 35—55 in 

The activation enthalpy and entropy are 24.7 0.4 kcal moh and 2.4 1.3 cal K mol respectively. The observed rate constants increase with increasing SnCla concentration, which may be explained by considering that the mechanism is a two-step process, but no definite conclusions could be reached. 

Current Radiopharmaceutical Synthesis. The aqueous chemistry of technetium is dominated by the oxidizing power of soluble TcO , and the thermodynamic stability of insoluble TcOa. All technetium-99m radiopharmaceuticals, except pertechnetate itself, are prepared by the aqueous reduction of pertechnetate in the presence of a potential ligand to prevent Tc02 deposition (2). The most commonly employed reductant is stannous chloride, although many other reductants can, and have, been used (1,2). 

While widely used, this procedure is subject to several difficulties and limitations, (a) It allows introduction of only one type of ligand, or one distribution of ligands, into the technetium radiopharmaceuticaL (b) It does not allow specific control over the final oxidation state, coordination number, coordination geometry, etc. of the technetium in the Tc-L product, (c) The reductant, especially Sn, is often incorporated into the final product (1,6). (d) The excess reductant is injected into the patient tindl) has a long biological half-life (7) and causes several deleterious side effects (8). 

In addition, it is very unlikely for the general redox procedure described by eq. 1 to yield a single, well-defined product complex. Since 

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

Synthesis by Substitution Routes. Many of the limitations inherent in the redox route described above can be avoided by preparation of technetium-99m radiopharmaeeutieals by a substitution route, i.e. the classical substitution of ligands onto a pre-reduced and isolated technetium center. Substitution routes allow control over the oxidation state and ligand environment of the technetium product, and permit the synthesis of complexes containing different ligands. By substitution routes it should be possible to prepare series of complexes in which some ligands are held fixed while others are varied in a systematic fashion to affect biological specificity. 

This salt can be prepared by the action of hydrochloric acid upon metallic tin, but since the action is exceedingly slow, it is hastened by the addition of a very small quantity of nitric acid, which oxidizes the tin. Nitric acid is ordinarily reduced only to the oxide NO by its action upon a metal but in the course of this preparation no red fumes of oxides of nitrogen are found to escape, because, under the influence of tin and stannous chloride, the reduction does not stop at nitric oxide, but continues to the lowest possible step, which is ammonia or in this case its salt, ammonium chloride. Stannous salts are oxidized quite readily to stannic by the oxygen of the air to prevent this happening during the evaporation of the solution, an excess of metallic tin is kept in the liquid. 

Apparatus shredded asbestos suspended in water, suction filter and trap bottle. 

8-inch porcelain dish, iron ring and ring stand. 

Explain why during this preparation no red oxides of nitrogen are seen to escape in consequence of the reduction of nitric acid by the metal. If nitric acid is reduced to NH3, show how many more equivalents of oxygen it will yield for the oxidation of the tin than if it were reduced only to NO. 

To test for the presence of ammonium salt in the product, take about 1 gram of the crystals dissolve in 10 cc. of water in a small beaker. Add sodium hydroxide solution until the precipitate first formed redissolves. Place over the beaker a watch glass, on the under side of which is stuck a piece of moistened red litmus paper. Place some cold water in the hollow of the watch glass, and warm the solution in the beaker very gently. What observation will indicate the presence of ammonium salt, and why  

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Tin(ll) chloride, SnCl2, stannous chloride. M.p. 247 - C. While solid (Sn plus gaseous HCl), forms hydrates (SnCl2,2H20 is tin salt) from Sn and aqueous HCl. Acts as acceptor in complexes and forms complexes with transition metals. Used as a mordant. 

Both aliphatic and aromatic nitro-compounds can be readily reduced in acid solution to the corresponding primary amine. Thus when a mixture of nitrobenzene and tin is treated with hydrochloric acid, the tin dissolves to give stannous chloride, SnCh, which in these circumstances then reacts with more acid to give stannic chloride, SnCl, and the nascent hydrogen produced from... 

CgH,N,Cl -h zSnCl, + 4HCI = CeHjNH NH, HCl + zSnCI when treated with an acid solution of stannous chloride (e.g., a solution in hydrochloric acid) but the yields are not as high as those obtained by the above sulphonate method. 

A similar reaction occurs when an aqueous solution of a diazonium compound is made strongly alkaline and then warmed with an alkaline solution of stannous chloride. This reaction, however, involves the intermediate formation of the... 

Required Benzeneazo-naphthol from above experiment methylated spirit, 100 ml. stannous chloride, 22 g. hydrochloric acid, 60 ml. 

Absolute diethyl ether. The chief impurities in commercial ether (sp. gr. 0- 720) are water, ethyl alcohol, and, in samples which have been exposed to the air and light for some time, ethyl peroxide. The presence of peroxides may be detected either by the liberation of iodine (brown colouration or blue colouration with starch solution) when a small sample is shaken with an equal volume of 2 per cent, potassium iodide solution and a few drops of dilute hydrochloric acid, or by carrying out the perchromio acid test of inorganic analysis with potassium dichromate solution acidified with dilute sulphuric acid. The peroxides may be removed by shaking with a concentrated solution of a ferrous salt, say, 6-10 g. of ferrous salt (s 10-20 ml. of the prepared concentrated solution) to 1 litre of ether. The concentrated solution of ferrous salt is prepared either from 60 g. of crystallised ferrous sulphate, 6 ml. of concentrated sulphuric acid and 110 ml. of water or from 100 g. of crystallised ferrous chloride, 42 ml. of concentrated hydiochloric acid and 85 ml. of water. Peroxides may also be removed by shaking with an aqueous solution of sodium sulphite (for the removal with stannous chloride, see Section VI,12). 

It is recommended that the tsopropanol be tested for peroxides and, if present, removed by refluxing with solid stannous chloride (for details, see concluding paragraph of Section VI,12)... 

Dioxan develops appreciable quantities of peroxides upon exposure to air or upon keeping. These can be eliminated by refluxing over anhydrous stannous chloride (compare Section VI, 12) or by filtration through a column of activated alumina. 

Anhydrous stannous chloride. Crystalline stannous chloride, SnCl2.2HjO, is heated for one hour in an oil bath at 195-200°, the cooled melt is powdered, and kept in a desiccator or in a tightly stoppered bottle. 

CAUTION. Ethers that have been stored for long periods, particularly in partly-filled bottles, frequently contain small quantities of highly explosive peroxides. The presence of peroxides may be detected either by the per-chromic acid test of qualitative inorganic analysis (addition of an acidified solution of potassium dichromate) or by the liberation of iodine from acidified potassium iodide solution (compare Section 11,47,7). The peroxides are nonvolatile and may accumulate in the flask during the distillation of the ether the residue is explosive and may detonate, when distilled, with sufficient violence to shatter the apparatus and cause serious personal injury. If peroxides are found, they must first be removed by treatment with acidified ferrous sulphate solution (Section 11,47,7) or with sodium sulphite solution or with stannous chloride solution (Section VI, 12). The common extraction solvents diethyl ether and di-tso-propyl ether are particularly prone to the formation of peroxides. 

From nitriles by treatment with anhydrous Stannous chloride dissolved in ether saturated with hydrogen chloride the resulting crystaUine aldimine stannichloride, [(RCH=NHj)2] SnCl, or (RCH=NH,HCl)2SnCl4, is hydrolysed by warm water, and the aldehyde is isolated by distillation with steam or by extraction with a solvent (Stephen reaction), for example, for R = CH3(CH2)4, i.e., n-amyl ... 

Into a 500 ml. three-necked flask, provided with a mechanical stirrer, a gas inlet tube and a reflux condenser, place 57 g. of anhydrous stannous chloride (Section 11,50,11) and 200 ml. of anhydrous ether. Pass in dry hydrogen chloride gas (Section 11,48,1) until the mixture is saturated and separates into two layers the lower viscous layer consists of stannous chloride dissolved in ethereal hydrogen chloride. Set the stirrer in motion and add 19 5 g. of n-amyl cyanide (Sections III,112 and III,113) through the separatory funnel. Separation of the crystalline aldimine hydrochloride commences after a few minutes continue the stirring for 15 minutes. Filter oflF the crystalline solid, suspend it in about 50 ml. of water and heat under reflux until it is completely hydrolysed. Allow to cool and extract with ether dry the ethereal extract with anhydrous magnesium or calcium sulphate and remove the ether slowly (Fig. II, 13, 4, but with the distilling flask replaced by a Claisen flask with fractionating side arm). Finally, distil the residue and collect the n-hexaldehyde at 127-129°. The yield is 19 g. 

It is advisable to test a small portion of the filtrate for platinum by acidifying with hydrochloric acid and adding a few drops of stannous chloride solution a yellow or brown colour develops according to the quantity of platinum pVesent. The yellow colour is soluble in ether, thus rendering the t t more sensitive. If platinum is found, treat the filtrate with excess of formaldehyde and sodium iQrdroxide solution and heat,- platinum black septarates on standing and may be filtered and worked up with other platinum residues (see Method 3). 

Sn + 2HC1 —> SnCli + 2H stannous chloride is itself an excellent reducing agent ... 

It is interesting to note that azo dyestuffs may be conveniently reduced either by a solution of stannous chloride in hydrochloric acid or by sodium hyposulphite. Thus phenyl-azo-p-naphthol 3delds both aniline and a-amino-p-naphthol (see formula above), and methyl orange gives p-aminodimethylaniline and sulphanilic acid ... 

Reduction of methyl orange to />-aminodimethylaniline. Method 1. Dissolve 2 0 g. of methyl orange in the minimum volume of hot water and to the hot solution add a solution of 8 g. of stannous chloride in 20 ml. of concentrated hydrochloric acid until decolourisation takes place gentle boiling may be necessary. Cool the resulting solution in ice a crystalline precipitate consisting of sulphanilic acid and some p-aminodimethylaniline hydrochloride separates out. In order to separate the free base, add 10 per cent, sodium hydroxide solution until the precipitate of tin hydroxide redisaolves. Extract the cold solution with three or four 20 ml. portions of ether, dry the extract... 

It may also be prepared by the reduction of phenyldiazonium chloride with the calculated amount of a solution of stannous chloride in hydrochloric acid, but the yield is not so high as that obtained by the above sulphite method ... 

Compounds containing two primary amino groups attached to a benzene ring can be prepared by the reduction of dinitro compounds and of nitroanilines, usually with tin or stannous chloride and hydrochloric acid or with iron and very dilute hydrochloric acid. / ara-diamines may also be obtained by the reduction of aromatic amino-azo compounds (e.g., p-aminodimethylanihne from methyl orange, see Section IV,78). p-Phenylenediamine may also be prepared from p-nitroacetanilide reduction with iron and acid yields p-amino-acetaniUde,.which may be hydrolysed to the diamine. 

The crude o-phenylenediamine may be converted into the dihydrocliloride and the salt purified in the following manner. Dissolve it in 60 ml. of concentrated hydrochloric acid and 40 ml. of water containing 2 g. of stannous chloride, and treat the hot solution with 2-3 g. of decolourising carbon. Filter, add 100 ml. of concentrated hydrochloric acid to the hot colourless filtrate, and cool in a freezing mixture of ice and salt. Collect the colourless crystals of the dihydrochloride on a Buchner or sintered glass funnel, wash with a small volume of concentrated hydrochloric acid, and dry in a vacuum desiccator over sodium hydroxide. The yield is 61 g. 

Recovery of the wopropyl alcohol. It is not usually economical to recover the isopropyl alcohol because of its lo v cost. However, if the alcohol is to be recovered, great care must be exercised particularly if it has been allowed to stand for several days peroxides are readily formed in the impure acetone - isopropyl alcohol mixtures. Test first for peroxides by adding 0-6 ml. of the isopropyl alcohol to 1 ml. of 10 per cent, potassium iodide solution acidified with 0-6 ml. of dilute (1 5) hydrochloric acid and mixed with a few drops of starch solution if a blue (or blue-black) coloration appears in one minute, the test is positive. One convenient method of removing the peroxides is to reflux each one litre of recovered isopropyl alcohol with 10-15 g. of solid stannous chloride for half an hour. Test for peroxides with a portion of the cooled solution if iodine is liberated, add further 5 g. portions of stannous chloride followed by refluxing for half-hour periods until the test is negative. Then add about 200 g. of quicklime, reflux for 4 hours, and distil (Fig. II, 47, 2) discard the first portion of the distillate until the test for acetone is negative (Crotyl Alcohol, Note 1). Peroxides generally redevelop in tliis purified isopropyl alcohol in several days. 

A cousin to this reduction is one using stannous chloride (a.k.a. SnCb, a.k.a. Tin chloride) which is done exactly as the calcium one except that about lOOg of SnCb is used in place of the Mg or Ca and the addition occurs at room temperature and the solution is stirred for one hour rather than 15 minutes. Some very good reductions that operate almost exclusively at room temperature with no pressure and give almost 100% yields are to follow. The only reason Strike did not detail these methods is that some of the chemicals involved are a little less common than Strike is used to but all are available to the public. These alternatives include acetlylacetone and triethylamine [73], propanedithlol and trieth-ylamine [74], triphenylphosphine [75], NaBH4 with phase transfer catalyst [76], H2S and pyridine [77], and palladium hydrox-ide/carbon with hydrazine [78], stannous chloride dihydrate [85]. 

A sodium stannite solution was prepared by addition of aqueous sodium hydroxide (2.5 mol, lOOg) to aqueous stannous chloride (0.25 mol, 56g). The initially formed precipitate redissolved to form a clear solution. This solution was gradually added to a solution of 16.3g (0.1 mol) phenyl-2-nitropropene in THF at room temperature. A slightly exothermic reaction ensued, and the reaction mixture was stirred for 30 min, a saturated sodium chloride solution was added, and the solution was extracted with ether and the pooled extracts were evaporated under vacuum to give essentially pure P2P oxime in 80% yield. 

The Stephen s method allows the reduction of nitriles by stannous chloride in acid medium. If the amine chlorhydrate initially formed is hydrolyzed, the corresponding aldehyde is obtained (37, 91). Harington and Moggridge (37) have reduced 4-methyl-5-cyanothiazole by this method (Scheme 23). However, Robba and Le Guen (91) did not obtain the expected products with 4.5-dicyanothiazole and 2-methyl-4,5-dicyanothiazole. These compounds have been reduced with diisobutyl-aluminium hydride with very low yields (3 to 6%) (Scheme 24). In other conditions the reaction gives a thiazole nitrile aldehyde with the same yield as that of the dialdehyde. 

As mentioned previously, aldehydes can be prepared by Stephen s method of reduction of nitriles by stannous chloride (37, 91). Polaro-graphic reduction of thiazolecarboxylic acids and their derivatives gives lower yields of aldehydes (58). Ozonolysis of styrylthiazoles, for example, 2-styryl-4-methylthiazole, followed by catalytic reduction gives aldehyde with 47% yield of crude product (30). 

Stannous chloride, SnClj THjO—0.5N 56 g per liter. The water should be acid with HCl and some metallic tin should be kept in the bottle. 

The other important direct alkylation processes involve reaction of electron-rich olefinic compounds with either tin metal or stannous chloride (tin(II) chloride) in the presence of stoichiometric amounts of hydrogen chloride (22). Butyl acrylate (R = C Hg) was used commercially in this process to prepare the estertin or P-carboalkoxyethyltin chlorides as iHustrated in the foUowing. 

Many kits contain the indicated biologically active ingredient in a lyophilized form with stannous chloride. A Tc-labeled radiopharmaceutical, which can be used for six hours, is formed when mixed with Tc pertechnetate. Preparation of the agent is at room temperature, unless otherwise stated. Technetium-99m. Available Tc kits are Hsted below. 

The determination of tin in metals containing over 75 wt % tin (eg, ingot tin) requites a special procedure (17). A 5-g sample is dissolved in hydrochloric acid, reduced with nickel, and cooled in CO2. A calculated weight of pure potassium iodate (dried at 100°C) and an excess of potassium iodide (1 3) are dissolved in water and added to the reduced solution to oxidize 96—98 wt % of the stannous chloride present. The reaction is completed by titration with 0.1 Af KIO —KI solution to a blue color using starch as the indicator. 

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