Subject thallium

Concentrations of thallium in the blood or urine of unexposed subjects are usually less than 0.01 iLig/ml. Clinical symptoms of intoxication are associated with blood concentrations of about 0.1 iLig/ml values of 8 to 10 LLg/ml have been reported. Urinary concentrations of up to 20 LLg/ml may be seen in exposed subjects. Thallium salts are highly toxic and doses of about 12 mg/kg of a soluble salt may be fatal. 

The reaction is a sensitive one, but is subject to a number of interferences. The solution must be free from large amounts of lead, thallium (I), copper, tin, arsenic, antimony, gold, silver, platinum, and palladium, and from elements in sufficient quantity to colour the solution, e.g. nickel. Metals giving insoluble iodides must be absent, or present in amounts not yielding a precipitate. Substances which liberate iodine from potassium iodide interfere, for example iron(III) the latter should be reduced with sulphurous acid and the excess of gas boiled off, or by a 30 per cent solution of hypophosphorous acid. Chloride ion reduces the intensity of the bismuth colour. Separation of bismuth from copper can be effected by extraction of the bismuth as dithizonate by treatment in ammoniacal potassium cyanide solution with a 0.1 per cent solution of dithizone in chloroform if lead is present, shaking of the chloroform solution of lead and bismuth dithizonates with a buffer solution of pH 3.4 results in the lead alone passing into the aqueous phase. The bismuth complex is soluble in a pentan-l-ol-ethyl acetate mixture, and this fact can be utilised for the determination in the presence of coloured ions, such as nickel, cobalt, chromium, and uranium. 

In analogous reactions arylmetal compounds of thallium (ArTICl, addition of Tl-Na alloy, Nesmeyanov and Makarova, 1952), of tin (Ar2SnCl2, addition of Sn, Nesmeyanov et al., 1936), of lead (Ar4Pb, Pb-Na alloy, Nesmeyanov and Makarova, 1954 Nesmeyanov et al., 1954) were obtained (yields up to 80% with Hg, 10-40% with the other metals). Tetravalent metal salts often react to give a mixture of partially arylated metal chlorides (ArwMCl4 , n = 1 to 3). Waters (1939) was one of the few chemists outside Nesmeyanov s school who worked on that subject (arylation of lead). 

With the ArH ArTlX2 Arl reaction sequence available as a rapid and reliable probe for aromatic thallation, a detailed study was undertaken of the various factors affecting orientation in this electrophilic metallation process (153). The results, which are summarized below, demonstrate that aromatic thallation is subject to an almost unprecedented degree of orientation control coupled with the ease with which thallium can then be displaced by other substitutent groups (this aspect of the synthetic exploitation of aromatic thallation is discussed in detail below), the sequential processes of thallation followed by displacement represent a new and versatile method for aromatic substitution which both rivals and complements the classic Sandmeyer reaction. 

One of the most famous applications in forensic science is the analysis of Napoleon s hair by ICP-MS after mineralization in concentrated nitric acid whereby an arsenic concentration about 40 times higher than normal (about 40p,gg 1) was measured (see Section 9.5). Ingested arsenic is known to be stored in sulfydryl rich tissue, like hair, nails or skin. ETV-ICP-MS combined with isotope dilution has been employed to measure thallium in human scalp hair from a person poisoned by thallium compared to control subjects, whereby several longitudinal concentration gradients for the analyzed segments (length 10 mm) were obtained.28... 

The isotope 203Pb is produced by bombardment of thallium with protons in a cyclotron. The radioactive half-life is 52 h and decay is by electron capture. The associated 279-keV gamma ray enables the activity in the lung and other organs of volunteer subjects to be detected by external gamma ray spectrometers (Chamberlain etal., 1975). 

Yamamura and coworkers [158] developed an oxidative cyclization method to construct biphenyl ether bonds by thallium trinitrate (TTN) oxidation of the corresponding O,0 -dihalophenols followed by zinc reduction. The antibiotic piperazinomycin 266) was synthesized using this method as a key cyclization step [159]. As shown in Scheme 89, the diketopiperazine 263 was subjected to TTN oxidation in MeOH to afford an inseparable mixture containing plausible intermediate 264, which was directly reduced with zinc powder in AcOH-THF to give rise to the strained 14-membered biphenyl ether 265 in 19% yield together with two other isomers. 

The reactions of aromatic substrates with thallium reagents is a fascinating subject which has been reviewed by McKillop and Taylor,two of the prime contributors to this field of chemistry. Two types of reaction are possible, both of which are important for the introduction of oxygen functionality. Tlie fu t is electrophilic aromatic thallation, whilst the second involves one-electron oxidation. 

Later, this cycloaddition reaction was improved by the pretreatment of the enamide ester with an equimoler amount of trialkylsilyl trifluoromethanesul-fonate and triethylamine at ambient temperature. The synthesis of tyro-phorine (119) was achieved by the above improved method (Scheme 55). The enamide ester 441 was subjected to annulation using t-butyldimethylsilyl triflate and triethylamine at 15°C to produce the bicyclic lactam 442 in 68% yield. Oxidation of 442 with thallium(III) trifluoroacetate and boron triflu-oroetherate in a mixture of dichloromethane and trifluoroacetic acid at 4°C produced (83%) the pentacyclic compound 443. Hydrolysis of 443, followed by decarboxylation of the resultant acid, gave the pentacyclic lactam 444. Reduction of 444 with sodium bis(2-methoxyethoxy)aluminum hydride in refluxing dioxane afforded tyrophorine (119) (85CC1159). 

The nature of the bonding in the metal cyclopentadienyls and their derivatives is still the subject of much discussion, although the compounds have been known for some years. It is now quite certain that in the saltlike alkali, alkaline earth, and rare-earth metal cyclopentadienyls the bonding between the ring and the metal is essentially ionic. Compounds such as dicyclopentadienyl vanadium and chromium also show hydrolytic cleavage. On the other hand, however, cyclopentadienyl thallium, for which the recent investigations of Cotton and Reynolds (20) suggest an ionic bond, may be sublimed and is precipitated from an aqueous medium... 

The reaction between the acid chloride of chromone-2-carboxylic acid and ethyl ethoxymagnesioacetoacetate probably leads to the expected fi-diketone which enolizes and cyclizes spontaneously to spirofuranone(52).127 A different approach was made by Hungarian workers in their synthesis of tachrosin (53), an unusual kind of flavone isolated from Tephrosia poly-stachyoides and one of the earliest natural furanones to be isolated. They subjected an unsaturated ketone (Scheme 32) to oxidative rearrangement by thallium(III) salts, a reaction well known in chalcone chemistry, and eliminated methanol from the product to obtain the necessary starting material.128... 

Thallinm(ni) °, particnlarly as its triflnoroacetate salt , has been successfully used for the synthesis of phenols. This method can be carried out in a single step and is subject to isomer orientation control" . The aromatic compound to be hydroxylated is first thallated with thallium trifluoroacetate (TTFA)" and, by treatment with lead tetraacetate followed by triphenylphosphine and then dilute NaOH, it is converted to the corresponding phenol (equation 57). Table 1 shows some examples of these transformations . ... 

---