Removal of tin residues

Phenacyl esters of various N-a-Boc- N-a-Cbz- or tyN-dimethylamino-protected amino adds and dipeptides can be cleaved to the corresponding carboxylic acids on heating with bis(tributyltin)oxide in aprotic solvents [Scheme 6.72],23 There is no racemisation of the amino acid and peptide products. However there are some limitations to the method removal of tin residues from the product can diminish the yield and the Cbz group (but not a Boc) may undergo competitive cleavage. 

A number of demercurations of RHgX or RHgOR use tributyltin, or triphenyltin hydride,but complete removal of tin residues can sometimes be difficult NaBH4 reduction is then preferred. De-oxymercuration has also been observed during demercuration. The presence of anhydrous sodium acetate avoided this side reaction with PhsSnH, and the use of tributyltin hydride instead of NaBH4/NaOH in the demercuration of peroxymercurials led to much improved yields of peroxides (Scheme 33). 

Tin Chemistry Fundamentals, Frontiers and Appiications 5.5.2 Removal of Tin Residues by Partition between Two Phases... 

Chlorobenzaldehyde(2-nitrophenyl)hydrazone (3 g, 10.9 mmol) was heated under reflux with granulated tin (10 g) and coned hydrochloric acid (60 mL) for 1 h upon which an orange, clear solution was obtained, which became colorless on further heating. After the removal of tin, the solution was evaporated, almost to dryness, on a water bath to give a colorless, shiny, crystalline residue which was recrystallized (dil hydrochloric acid) to provide the hydrochloride mp 285 C. The free base was obtained as a colorless, crystalline mass after addition of NH3 to an aqueous solution of the hydrochloride, and was recrystallized (EtOH) to give shiny colorless plates mp 217-218 C. 

Load the oily product directly onto the top of the column. Remove the tin residues from the material by eluting with 500 mL of petroleum ether. The product can then be eluted using a 9 1 mixture of petroleum ether (40-60)/ethyl acetate. 

Clive and Wang have introduced a water-soluble variant of triphenyltin hydride that can be used for the Barton-McCombie reaction. Work-up involves basic or acidic work-up by washing the reaction products with an H2O/THF solution of LiOH or TsOH, respectively, to remove all tin residues. 

Reduction of a nitro compound to a primary amine. In a 50 ml. round-bottomed or conical flask fitted with a reflux condenser, place 1 g. of the nitro compound and 2 g. of granulated tin. Measure out 10 ml. of concentrated hydrochloric acid and add it in three equal portions to the mixtiue shake thoroughly after each addition. When the vigorous reaction subsides, heat under reflux on a water bath until the nitro compound has completely reacted (20-30 minutes). Shake the reaction mixture from time to time if the nitro compound appears to be very insoluble, add 5 ml. of alcohol. Cool the reaction mixture, and add 20-40 per cent, sodium hydroxide solution imtil the precipitate of tin hydroxide dissolves. Extract the resulting amine from the cooled solution with ether, and remove the ether by distillation. Examine the residue with regard to its solubility in 5 per cent, hydrochloric acid and its reaction with acetyl chloride or benzene-sulphonyl chloride. 

After the corrosion products had been removed from the surface of the metal to be analysed, a weighed sample was treated with moderately concentrated nitric acid and the reaction mixture was allowed to stand overnight... the supernatant liquid was poured off and saved, and any undissolved metal or insoluble residue again treated with nitric acid... If tin was present as shown by the continued presence of a residue insoluble in nitric acid, this was collected on filter paper... (this) was simply dried in an oven and weighed... a parallel control experiment was made with a known weight of pure tin. It was found from this that 100 parts of dried residue contained 71 parts metallic tin, in other words the gravimetric factor was 0.71. 

To 5.7 g (0.0527 mol) of p-benzoquinone is added 10 g (approximately 0.072 mol) of tin amalgam and 50 ml of glacial acetic acid. The mixture is heated on a steam bath. After 3 minutes green crystals of quinhydrone precipitate but soon dissolve to give a Ught yellow solution. After 0.5 hour the solution is filtered, the solvent is removed in vacuo, and the residue is recrystallized from benzene-acetone to give 5.0g (88%) of hydroquinone, m.p. 169-190°. 

Tin-based reagents are not always snitable owing to the toxicity of organotin derivatives and the difficulties often encountered in removing tin residues from the final product. Therefore, the same authors have carried out additional experiments with 17d and several different alkyl halides under tin-free conditions. The treatment of 16d with tert-butyldiphenylsilyl chloride (TBDPSCl) and triethylamine in the presence of silver triflate in CH2CI2 affords the bis(silyloxy)enamine 17d in 92% yield (Scheme 17). When the radical reaction was carried out with ethyl iodoacetate in the presence of 2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70) as the initiator in CH2CI2, the oxime ether 19 was obtained in 83% yield (Scheme 17). 

To a solution of 41 (448 mg) (Eq. (17)] in toluene (10 mL) was added TBTH (3 mmol) and a trace amount of AIBN. The solution was then heated under argon for 2.5 h at 110°C. After evaporation of the solvent, the residual foam was dissolved in acetonitrile (30 mL), and the solution was extracted three times with hexanes to remove several tin compounds. The acetonitrile was evaporated, and the residue was purified by chromatography over silica gel (40 g) to yield 165 mg (83%) of 42. 

Method A. 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 tin(n) chloride (Section 4.2.73, p. 465) and 200 ml of anhydrous ether. Pass in dry hydrogen chloride gas (Section 4.2.38, p. 438) until the mixture is saturated and separates into two layers the lower viscous layer consists of tin(n) chloride dissolved in ethereal hydrogen chloride. Set the stirrer in motion and add 19.4g (0.2 mol) of hexanenitrile (Expt 5.160) through the separatory funnel. Separation of the crystalline aldimine hydrochloride commences after a few minutes continue the stirring for 15 minutes. Filter off 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 calcium sulphate or magnesium sulphate and remove the ether slowly by distillation through a short fractionating column. Finally, distil the residue and collect the hexanal at 127-129 °C. The yield is 19 g (95%). 

A key step in tin-based reductions on the solid phase is the washing procedure, which is used for the removal of residual tin salts. To be on the safe side, numerous washes with a very broad spectrum of solvents are recommended. In our experience good results are obtained with polystyrene-based resins when washes with warm DMF/water (1 1) are included. 

It has been reported that low concentrations of tributyltin fluoride were readily transformed to tributyltin chloride in sea water (Strand 1983). Tributyltin has been shown to undergo slow photolysis (Maguire et al. 1983). The half-life of the photolysis reaction was estimated to be greater than 89 days. The direct photolysis of tributyltin in water initiates a sequential removal of the butyl groups, leading to inorganic tin as a residual. The reaction was much faster in the presence of fulvic acid (a major component of soil organic matter). 

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