Type III reactions

It is important not only that a multiplicity of compounds in the sample mixture may be selectively derivatized - as was shown for Type III reactions - but also that one racemate may be derivatized with a multiplicity of derivatizing agents (Fig. 7-17). Although this approach can be used to optimize the analogues of a compound [28, 29], it is of special interest when a compound is required to be separated on a preparative scale. 

In the oxygen-independent Type III reactions the excited/sensi-tized psoralen donates its excitation energy directly to, or reacts with, the target compound. This occurs if the substrate and the target compound (e.g., DNA) are already in close proximity or intercalated. The reactions will proceed very rapidly via the excited singlet state, and are, typically, cyclization reactions or electron-transfer between the sensitizer and the target. In addition, the psoralen can be ionized, either directly or via the excited state, and react with the target compound in the form of a radical cation. Furocoumarins are also employed in treatment of cutaneous T-cell lymphoma and some infections connected with AIDS, by so-called photopheresis processes [71, 74-76]. In this case, peripheral blood is exposed to, e.g., photoactivated (sensitized) 8-methoxypsoralen (8-MOP) in an extracorporeal flow system. This... 

Type III reactions are the result of antigen-antibody (IgG or IgM) complexes that accumulate in tissues or the circulation, activate macrophages and the complement system, and trigger the influx of granulocytes and lymphocytes (inflammation). Examples include an Arthrus reaction when soluble antigen is injected into the skin of a sensitized individual and serum sickness, which occurs 7 to 10 days following the administration... 

Intramolecular interactions have been classified as Norrish Type II and Type III reactions. 

Type III reaction involves intramolecular hydroge.i abstraction together with a-cleavage. 

Type III Reactions These reactions involve the presence of antigen-antibody complexes, particularly those formed as a result of the production of autoantibodies. These complexes deposit in various tissues and involve inflammatory cells as well as complement, resulting in tissue damage due to the production of proteolytic enzymes by polymorphonuclear leukocytes and macrophages. A number of autoimmune diseases result from these reactions. Some clinical examples include systemic lupus erythematosus, rheumatoid arthritis, immune complex glomerulonephritis, Arthus reaction and serum sickness. 

Type III reactions proceed by attack of a nucleophile at the central sp carbon of the allenyl system of the complexes 5. Reactions of soft carbon nucleophiles derived from active methylene compounds, such as /i-kcto esters or malonates, and oxygen nucleophiles belong to this type. The attack of the nucleophile generates the intermediates 9, which are regarded as the palladium-carbene complexes 10. The intermediates 9 pick up a proton from the active methylene compound and n-allylpalladium complexes 11 are formed, which undergo further reaction with the nucleophile, as expected, and hence the alkenes 12 are formed by the introduction of two nucleophiles. 

Type III reaction proceeds by an attack of a nucleophile at the central sp carbon of the allenylpalladium. Soft carbon nucleophiles such as / -keto esters and malonates react with propargylic carbonates under neutral conditions using DPPE as a ligand [35], The 2,3-disubstituted propenes 151 and 152 are obtained by the reaction of 2-propynyl carbonate (145) with two moles of malonate under neutral conditions in... 

Reverse of Type I and II reactions are Type III reactions. As stated in the introduction, abundant experimental data and mechanistic studies indicate that these catalytic disproportionation reactions proceed in accordance with a reaction scheme that can be pictured as follows ... 

Statistically, the rate of formation of new olefins for Type II reactions, except in some cases involving branched olefins, is twice the rate for Type I reactions both alignments of the double-bond isomers to form the transition state will result in products different from the reactants. For Type III reactions three situations can exist depending on the reactants, both, only one, or neither alignment of the olefins will form a four-center transition state that dissociates into new olefins. Cleavage of 2-butene with propylene will not form new olefines however, cleavage of 2-butene with ethylene will form propylene. 

Examples of the disproportionation of dissimilar olefins, Type III reactions, are shown in Table 8. Alpha olefins were produced by disproportionating... 

Table 8. Disproportionation of dissimilar olefins Type III reactions A+B ( 1 P+Q...

Immune complex A complex of antibody(ies) and antigen(s) that may lead to pathological consequences such as inflammation or blockage of a vessel (i.e., a type III reaction). 

Figure 24 illustrates the dependence of Type III selectivity on intraparticle and interphase diffusion effects by plotting the apparent overall selectivity from eqs 159, 167 and 168 for Bim/fa = 1, against the conversion of reactant Ai. From this figure, it appears that the influence of intraparticle diffusion may reduce the overall selectivity in Type III reactions by a factor of about two. Wheeler [113] reported that this degree of reduction is independent of the intrinsic selectivity factor AA . It may therefore serve as a general rule of thumb. 

Again, this was for isothermal conditions. In non-isothermal Type III reactions, a deviating temperature will also impose additional effects on selectivity, once the activation energies of the two reactions differ sig-... 

Figure 24. Variation of the apparent selectivity with conversion for a Type III reaction. Comparison of the results obtained under kinetic and diffusion control (isothermal conditions, intrinsic selectivity factor Ak = 4, equal Biot numbers Bim, — Bim2, initial concentration C2,o = 0).

Type III reactions are caused by tissue injury due to immune complexes. The antigen-antibody complexes are usually cleared by the immune system however, repeated contact with antigens can cause the complex to deposit in tissue and result in tissue injury. Serum sickness is the classic example of a Type III reaction. Medications associated with serum sickness include many antibiotics, phenytoin, salicylates, barbiturates, nonsteroidal antiinflammatory drugs, isoniazid, antisera, hydralazine, captopril, and sulfonamides. Procainamide-induced lupus, described in Chapter 16, is also considered a Type III reaction. 

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