Reductive Dealkylation

Aryl and alkyl hydroxylations, epoxide formation, oxidative dealkylation of heteroatoms, reduction, dehalogenation, desulfuration, deamination, aryl N-oxygenation, oxidation of sulfur Oxidation of nucleophilic nitrogen and sulfur, oxidative desulfurization Oxidation of aromatic hydrocarbons, phenols, amines, and sulfides oxidative dealkylation, reduction of N-oxides Alcohol oxidation reduction of ketones Oxidative deamination... 

Reductive Dealkylation Reductive dealkylation involves replacement of an alkyl group on a heteroatom by hydrogen. The reaction is considered to be mainly biologically mediated and usually is important in the subsurface for transformation of agrochemicals. 

Disposition in the Body. Readily absorbed after oral administration. Metabolised by A-dealkylation, reduction, deamination, and A-hydroxylation primarily to active metabolites keto-reduction is stereoselective resulting in the formation of threo-hydroxylated metabolites glucuronide formation also occurs along with the formation of hippuric and mandelic acids. About 80 to 90% of a dose is excreted in the urine the amount excreted in the urine is reduced when the urine is alkaline of the urinary excreted material, A-ethylaminopropiophenone, norephedrine (phenylpropanolamine), and hippuric acid are the main metabolites together with small amounts of unchanged drug, amino-propiophenone, A-diethylnorephedrine, and A-ethylnor-ephedrine. 

Several mechanisms are involved in degradation, among them, dealkylation, reduction, oxidation, hydrolysis and combinations of these. Degradation products do not accumulate in the soil, and none of the degradation products are to be found in quantities greater than 4% of the total herbicide initially applied. Nonextract-able, so-called soil-bound degradation products located in the fulvic acid and humic acid fractions of the soil are formed in substantial quantities. 

Probst et al. (1966) conclude from their experiments that trifluralin is not metabolised in soybean and cotton. The same authors, as well as Golab et al. (1967), observed in carrots dealkylation, reduction and the oxidation of the trifluoromethyl group into carboxyl, though the major part of trifluralin remained unchanged. Hamilton and Biswas (1967) found in sweet potato and peanut 87% degradation 72 hours after treatment with trifluralin, and in peanut 99% metabolisation. 

The first catalyst used by Ziegler et al. [5,82] for the polymerization of ethene was a mixture of TiCU and A1(C2H5)3, each of which is soluble in hydrocarbons. In combination they form an olive-colored insoluble complex that is very unstable. Its behavior is very sensitive to a number of experimental parameters, such as Al/Ti ratio, temperature and time of mixing of all components, and absolute and relative concentrations of reactants [83]. After complexation, TiC is reduced by a very specific reduction process. This reduction involves alkylation of TiC with aluminum alkyl molecules followed by a dealkylation reduction to a trivalent state ... 

It has already been mentioned that the degradation of s-triazine herbicides such as atrazinc in soil can be described by two reaction types only, hydrolysis and reductive dealkylation (see Figure 10.3-8). Application oF these two reaction types to a specific s-triazinc compound such as atrazinc provides the reaction network shown in Figure 10,3-12. This can also be vcriFicd by running this example on h ttp //www2,chemie,uni-erlangen.de/semces/eros/,... 

Biotransformation reactions can be classified as phase 1 and phase 11. In phase 1 reactions, dmgs are converted to product by processes of functionalization, including oxidation, reduction, dealkylation, and hydrolysis. Phase 11 or synthetic reactions involve coupling the dmg or its polar metaboHte to endogenous substrates and include methylation, acetylation, and glucuronidation (Table 1). 

A study of the degradation of two azo disperse dyes. Disperse Orange 5 [6232-56-0] (1) Cl 11100) and Disperse Red 5 [3769-57-1] Cl 11215) showed reduction of the azo linkage into aromatic amines and further dealkylation to -phenylene-diamine [106-50-3] (2) (255). 

Fenoldopam (76) is an antihypertensive renal vasodilator apparently operating through the dopamine system. It is conceptually similar to trepipam. Fenoldopam is superior to dopamine itself because of its oral activity and selectivity for dopamine D-1 receptors (D-2 receptors are as.sociated with emesis). It is synthesized by reduction of 3,4-dimethoxyphenylacetonitrile (70) to dimethoxyphenethylamine (71). Attack of diis last on 4-methoxystyrene oxide (72) leads to the product of attack on the epoxide on the less hindered side (73). Ring closure with strong acid leads to substituted benzazepine 74. O-Dealkylation is accomplished with boron tribromide and the catechol moiety is oxidized to the ortho-quinone 75. Treatment with 9NHC1 results in conjugate (1,6) chloride addition and the formation of fenoldopam (76) [20,21]. 

The numerous biotransformations catalyzed by cytochrome P450 enzymes include aromatic and aliphatic hydroxylations, epoxidations of olefinic and aromatic structures, oxidations and oxidative dealkylations of heteroatoms and as well as some reductive reactions. Cytochromes P450 of higher animals may be classified into two broad categories depending on whether their substrates are primarily endogenous or xenobiotic substances. Thus, CYP enzymes of families 1-3 catalyze... 

Owing to its low water solubility and high octanol/water partition coefficients, dinitroaniline herbicides adsorb and bind to soil macromolecules and show minimal leaching potential. Dinitroanilines herbicides show good soil residue activities with soil half-lives ranging from 30 days for benfluralin and oryzalin to 6-7 months for trifluralin. Al-Dealkylation (aerobic conditions) and reduction of the nitro group to an amino moiety (anaerobic conditions) have been reported as major soil degradation pathways. 

Dinitroaniline herbicides show minimal plant systematic translocation properties with the majority of the absorbed residues in the root tissues. Metabolites identified include traces of Al-dealkylation, alkyl and aryl hydroxylation and nitro reduction products. Low levels of dinitroaniline herbicide residues have been reported in raw agricultural commodities according to Good Agricultural Practice. 

The fate of the dinitroaniline herbicides in soil is extremely complex and many metabolites have been identified. Golab and Althaus reported 28 metabolites identified in a degradation study of trifluralin in soil. Major degradation products of dinitroaniline herbicides were formed by nitro reduction, A-dealkylation (mono-dealkylated and completely dealkylated) and the ring formation of benzimidazole. 

In the former case, the dibromo- or dichloro-substituted arene is reacted with cuprous or sodium thiolates to give vicinal thioethers, which can be reductively dealkylated, for example with Na/NH3, to give the dithiols.63 Alternatively, benzenethiol is reacted with ra-BuLi, and the resulting lithiated product is made to react with elemental sulfur to give the 1,2-dithiolate salt. 

Smith and Rosazza have suggested that microbial transformation experiments could best be carried out by using a series of perhaps 10 metabolitically prodigious microorganisms as microbial models. Microorganisms for such work may be selected on the basis of considerable literature precedence for their abilities to catalyze the desired biotransformation reaction (i.e., O-dealkylation, N-dealkylation, aromatic hydroxylation, and reductions). The alkaloid substrate... 

While the cytochrome P-450 monooxygenase reaction described in Eq. (1) often involves hydroxylation of carbon, many other reactions are catalyzed by these enzyme systems. These reactions include oxidation of nitrogen and sulfur, epoxidation, dehalogenation, oxidative deamination and desulfuration, oxidative N-, O-, and S-dealkylation, and peroxidative reactions (56). Under anaerobic conditions, the enzyme system will also catalyze reduction of azo, nitro, N-oxide, and epoxide functional groups, and these reductive reactions have been recently reviewed (56, 57). Furthermore, the NADPH-cytochrome P-450 reductase is capable of catalyzing reduction of quinones, quinonimines, nitro-aromatics, azoaromatics, bipyridyliums, and tetrazoliums (58). 

Unsymmetrical secondary aliphatic amines have been prepared by reaction of alkyl halides with benzylidene amines and subsequent hydrolysis 814 by reaction of alkyl halides with alkyl amines 5 by reduction of amine-aldehyde adducts 8-8 and by dealkylation of tertiary amines with dibenzoyl peroxide. ... 

Aromatics are typically included in gasolines to increase octane number. However, high aromatic content increases engine-out hydrocarbons and NOx emissions.16 Moreover, aromatics are the main precursors of exhaust benzene, a known carcinogenic, via dealkylation of substituted aromatics.17 Therefore, reduction of total aromatic content, together with olefin content, is an important part of California phase III reformulated gasoline specifications,18 with respect to the current allowed concentrations of benzene and total aromatics of 0.8 and 25 percent of volume, respectively. 

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