Iron-catalysed reactions

Beller, M. (2008) From Palladium to Iron-Catalysed Reactions for the Synthesis of Pharmaceuticals and Fine Chemicals, 26th SCI Process Development Symposium, 10-12 December 2008, Cambridge. 

Systems containing Sulphur as the only Heteroatom. - A variety of sulphur-containing cyclophanes were synthesized by the dilution principle, using an improved apparatus. The equipment will prove valuable in the preparation of many macrocyclic systems. The iron-catalysed reaction between bis-(2,4-dimethoxyphenyl) sulphide and S2CI2 gave four macrocyclic systems, including (47). The formation of (47) occurs by the unusual electrophilic cleavage of C-aryl-S bonds. 

Reaction (16) is a Fenton-type reaction (Fenton, 1894 Croft et al., 1992). There is still controversy as to whether the reaction of Cu+ and H2O2 leads to the formation of (HO) or even a Cu + species (Bielski and Cabelli, 1991). As for iron-catalysed reactions, Fenton chemistry probably involves (oxygen)iron(2-i-) [FeO] + intermediates, which are strong oxidants as well. The reaction of Fe +(chelate) -1- H2O2 could yield (O2), but is reported to be rather slow (Halliwell and Gutteridge, 1989, 1992 Chiueh et al., 1992). In vivo formation of (HO) is determined by measurement of hy-droxylated salicylic acid (Van Steveninck et al.,... 

Scheme 13.14 The iron-catalysed reaction between alkenes and Grignard reagents.

The iron-catalysed reaction of heteroarenes, including indoles, pyrroles, thiophene, and furan, with 3-methyl-2-quinonyl boronic acids allows the formation of alkylated products, such as (68), rather than the more usual alkenylated products. The unusual alkylation, at the 5-position, of oxindoles to give products such as (69) has been reported using the acid-catalysed reaction with benzylic alcohols in nitromethane. Silylation of indole, at the 3-position, to give (70) has been achieved using a cationic ruthenium(II) sulfide complex as a catalyst. A sulfur-stabilized silicon electrophile is formed resulting in a Wheland intermediate which is deprotonated by sulfur atom. ... 

NADH, which enters the Krebs cycle. However, during cerebral ischaemia, metabolism becomes anaerobic, which results in a precipitous decrease in tissue pH to below 6.2 (Smith etal., 1986 Vonhanweh etal., 1986). Tissue acidosis can now promote iron-catalysed free-radical reactions via the decompartmentalization of protein-bound iron (Rehncrona etal., 1989). Superoxide anion radical also has the ability to increase the low molecular weight iron pool by releasing iron from ferritin reductively (Thomas etal., 1985). Low molecular weight iron species have been detected in the brain in response to cardiac arrest. The increase in iron coincided with an increase in malondialdehyde (MDA) and conjugated dienes during the recirculation period (Krause et al., 1985 Nayini et al., 1985). 

The feature of xanthine oxidase which is no doubt of the greatest chemical interest, is the presence of several non-protein components. Much effort has been expended in attempting to elucidate the respective roles of iron, flavin and molybdenum in the various enzyme catalysed reactions. Numerous studies of the iron constituent have been made of late (45, 46, 47, 48, 49, 50), it having been found to be of the iron-sulphur (51 a, 51 b) type. Neither iron (19) nor molybdenum (31) can be removed reversibly from the enzyme, though the FAD can be (52, see below). 

Benzyl alcohol contaminated with 1.4% of hydrogen bromide and 1.1% of dissolved iron(II) polymerises exothermally above 100°C. Bases inhibit the polymerisation reaction. In a laboratory test, alcohol containing 1% of HBr and 0.04% of Fe polymerised at about 150° with an exotherm to 240° C. Formation and iron-catalysed poly-condensation of benzyl bromide seems to have been implicated. See Benzyl bromide Molecular sieve, or Catalytic impurities See Other BENZYL COMPOUNDS, POLYCONDENSATION REACTION INCIDENTS... 

The successive step in sample preparation is graphitization. Several different reactions can be used. The most well known is probably the iron-catalysed reduction of the collected C02 by reaction with hydrogen [71]... 

One of the characteristic features of the metal-catalysed reaction of acetylene with hydrogen is that, in addition to ethylene and ethane, hydrocarbons containing more than two carbon atoms are frequently observed in appreciable yields. The hydropolymerisation of acetylene over nickel—pumice catalysts was investigated in some detail by Sheridan [169] who found that, between 200 and 250°C, extensive polymerisation to yield predominantly C4 - and C6 -polymers occurred, although small amounts of all polymers up to Cn, where n > 31, were also observed. It was also shown that the polymeric products were aliphatic hydrocarbons, although subsequent studies with nickel—alumina [176] revealed that, whilst the main products were aliphatic hydrocarbons, small amounts of cyclohexene, cyclohexane and aromatic hydrocarbons were also formed. The extent of polymerisation appears to be greater with the first row metals, iron, cobalt, nickel and copper, where up to 60% of the acetylene may polymerise, than with the second and third row noble Group VIII metals. With alumina-supported noble metals, the polymerisation prod-... 

There are several modes of protection from the activity of available iron or copper in vivo. (Antioxidant action is discussed in more detail in Chapter 4). Apotransferrin binds iron(III) for transport and delivery to cells. It is its capacity as an iron-binding protein which renders it also able to function as an antioxidant by making iron(III) unavailable for participation in iron-catalysed radical reactions. Only about 30% of the iron-binding sites on the transferrin in human plasma are normally occupied in vivo (transferrin concentration 1.2-2.0mg/ml). The copper-containing protein caeruloplasmin (0.2-0.4 mg/ml) is... 

Clearly, in the normal individual, iron levels are under extremely tight control and there is little opportunity for iron-catalysed free radical generating reactions to occur. However, there are situations when the iron status can change, either locally, as in ischaemic tissue, or systematically, as with idiopathic haemochromatosis or transfusion-induced iron overload. In such circumstances, abnormal levels of iron can induce toxic symptoms. 

At present it is difficult to distinguish between the different oxygen-radical generating systems in relation to ischaemia/reperfusion-induced tissue injury. It is likely that the formation of oxygen radicals occurs as a result of metabolic processes and that redox-active metal catalysed reactions and the beneficial effects of iron chelators are due to both chelation of the metal and their radicalscavenging properties. 

From the known chemical properties of superoxide free radicals and hydrogen peroxide, it is unlikely that these two species will react directly with the range of biomolecules found in synovial fluid. It is more likely, particularly for superoxide radicals, that they will instead participate in redox reactions with complexes of metal ions such as iron and copper, although reaction with phenolic compounds cannot be excluded. It has been proposed therefore that synovial fluid, in particular hyaluronic acid, can be degraded in vivo through an iron-catalysed Haber-Weiss reaction. 

Fluxes of superoxide radical ions produced in vivo or in vitro in the presence of transition-metal complexes of copper(II) and iron(II) or iron(III) may lead to the formation of the highly reactive hydroxyl radical via metal-catalysed reactions such as described above (Reactions 1, 2). The efficiency of hydroxyl-radical... 

---