Other Free-Radical-Producing Agents

Many naturally occurring antioxidants are derivatives of phenol and hindered phenols, such as di-tert-butyl paracresol (Equation 15.14). It has the ability to act as a chain transfer agent forming a stable free radical that does not initiate chain radical degradation. However, the phenoxy free radical may react with other free radicals producing quinone derivatives. 

The agent responsible for autocatalytic behavior need not be the product of the reaction, it can be an intermediate. Low-temperature oxidation of methane provides an example [59,85], The key free radical turns out to be CH3-, produced from methane by initiation and giving rise to other free radicals. The propagation mechanism with six interlocking steps and chain branching is such that build-up of CH3- accelerates the rate (see Figure 9.4, previous page). 

Continuous chlorination of benzene at 30—50°C in the presence of a Lewis acid typically yields 85% monochlorobenzene. Temperatures in the range of 150—190°C favor production of the dichlorobenzene products. The para isomer is produced in a ratio of 2—3 to 1 of the ortho isomer. Other methods of aromatic ring chlorination include use of a mixture of hydrogen chloride and air in the presence of a copper—salt catalyst, or sulfuryl chloride in the presence of aluminum chloride at ambient temperatures. Free-radical chlorination of toluene successively yields benzyl chloride, benzal chloride, and benzotrichloride. Related chlorination agents include sulfuryl chloride, tert-huty hypochlorite, and /V-ch1orosuccinimide which yield benzyl chloride under the influence of light, heat, or radical initiators. 

This was also accomplished with BaRu(0)2(OH)3. The same type of conversion, with lower yields (20-30%), has been achieved with the Gif system There are several variations. One consists of pyridine-acetic acid, with H2O2 as oxidizing agent and tris(picolinato)iron(III) as catalyst. Other Gif systems use O2 as oxidizing agent and zinc as a reductant. The selectivity of the Gif systems toward alkyl carbons is CH2 > CH > CH3, which is unusual, and shows that a simple free-radical mechanism (see p. 899) is not involved. ° Another reagent that can oxidize the CH2 of an alkane is methyl(trifluoromethyl)dioxirane, but this produces CH—OH more often than C=0 (see 14-4). ... 

The free radical polymerization of HPMA in the presence of mercaptans involves two different initiation mechanisms (Scheme 2) [26]. One is the initiation by RS radicals from chain transfer agent the other appears to be the direct initiation by the primary isobutyronitrile (IBN) radicals formed by the decomposition of AIBN [27]. The RS are formed by either the free radical transfer reaction of alkyl mercaptans with the IBN radicals or the chain transfer reaction of an active polymer chain with the mercaptans. The initiation by the RS radicals produces the ST polymers with a functional group at one end of the polymer chain. The initiation by IBN radicals leads to nonfunctional polymer chains with an IBN end group. The presence of the polymers with IBN end groups effects the purity and the functionality of ST polymers. As expected, the production of nonfunctionalized polymer chains is affected by reaction conditions. The polymerization is mainly terminated by chain transfer reaction with the mercaptans, but other termination mechanisms, such as disproportionation and recombination, take place depending on the reaction conditions [26]. 

For treatment by the ZPU, a waste stream must be in the vapor phase at near-ambient pressure, at a temperature of less than 400°F, and relatively free of particulate matter. Each compound in the waste stream has unique requirements for destruction. Many compounds are destroyed with a low application of energy, while others require a stronger application. The dose required for a specific combination of contaminants must be determined experimentally. Moisture may either enhance or reduce system effectiveness depending on the mixture. Compounds that act as free-radical scavengers or reducing agents may diminish the process efficiency. Concentrations of vapors that produce temperatures above 400°F in the reaction chamber through exothermic reaction must be diluted to keep the temperature below 400°F. 

In this reaction (demonstrated in vitro), one of the two radicals is oxidizing while the other is reducing. In vivo, this reaction is catalyzed by one of several isoforms of an enzyme known as superoxide dismutase (SOD). As shown above, hydrogen peroxide may form as a result of the superoxide anion s dismutation reaction however, it may also be produced from a bivalent reduction of 02. The addition of the second electron leads to the formation of hydrogen peroxide, which is a powerful oxidizing agent. Due to the unpaired electrons in their outer shells, free radicals are favored to pair with other molecules during bimolecular collisions. 

Removable cation-stabilizing auxiliaries have been investigated for polyene cyclizations. For example, a silyl-assisted carbocation cyclization has been used in an efficient total synthesis of lanosterol. Other conditions for the cyclization of polyenes and of ene-ynes to steroids have been investigated. Oxidative free-radical cyclizations of polyenes produce steroid nuclei with exquisite stereocontrol Besides the aforementioned A-ring aromatic steroids and contraceptive agents, partial synthesis from steroid raw materials has also accounted for the vast majority of industrial-scale steroid synthesis. 

The main dose-limiting toxicity of all anthracyclines is myelosuppression, with neutropenia more commonly observed than thrombocytopenia. In some cases, mucositis is dose-limiting. Two forms of cardiotoxicity are observed. The acute form occurs within the first 2-3 days and presents as arrhythmias or conduction abnormalities, other electrocardiographic changes, pericarditis, and myocarditis. This form is usually transient and is asymptomatic in most cases. The chronic form results in a dose-dependent, dilated cardiomyopathy associated with heart failure. The chronic cardiac toxicity appears to result from increased production of free radicals within the myocardium. This effect is rarely seen at total doxorubicin dosages below 500-550 mg/m2. Use of lower weekly doses or continuous infusions of doxorubicin appear to reduce the incidence of cardiac toxicity. In addition, treatment with the iron-chelating agent dexrazoxane (ICRF-187) is currently approved to prevent or reduce anthracycline-induced cardiotoxicity in women with metastatic breast cancer who have received a total cumulative dose of doxorubicin of 300 mg/m2. All anthracyclines can produce "radiation recall reaction," with erythema and desquamation of the skin observed at sites of prior radiation therapy. 

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