S-dealkylation

Complexes of alkyl-linked o-benzenedithiolates eliminate ethylene to give benzenedithiolato complexes (Eq. 27) (275-277). This reaction is the reverse of the known addition of alkenes to bis(dithiolene) complexes (278-281). Photolysis of the S-benzylated dithiolenes M(PhCH2S2C2Ph2)2 (M = Ni, Pd, Pt) results in S-dealkylation with elimination of benzyl radicals (282). In general, however, the properties of S-alkylated dithiolenes have not been 

4-Dithiin derivatives (dithiabenzenes) have long been known to react with metal carbonyls to give dithiolenes (285). A recent illustration is provided by the finding that treatment CpCo(CO)2 with 2-nitro-3,5-diphenyl-l,4-dithiin affords CpCoS2C2(Ph)H (286). 

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A specific feature of the coordinated (heavier) chalcogenoethers is their ability to undergo E-C bond cleavage under certain conditions. For sulfur this process (S-dealkylation) has been known for many years,1 however, Se/Te-dealkylation also occurs.134,140 Relatively few systems have been characterized... 

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). 

Although UGTs catalyze only glucuronic acid conjugation, CYPs catalyze a variety of oxidative reactions. Oxidative biotransformations include aromatic and side chain hydroxylation, N-, O-, S-dealkylation, N-oxidation, sulfoxidation, N-hydroxylation, deamination, dehalogenation and desulfation. The majority of these reactions require the formation of radical species this is usually the rate-determining step for the reactivity process [28]. Hence, reactivity contributions are computed for CYPs, but a different computation is performed with the UGT enzyme (as described in Section 12.4.2). 

N-,0-,S-dealkylation N-, 0- or S-alkyl derivatives Flavine monooxygenases thiol compounds N-oxides... 

As was already shown in Scheme 11, benzothiazine ylides have a nucleophilic nitrogen that was protonated with loss of the A-alkyl group even when heated in dimethyl sulfoxide (DMSO). Reacting the ylides 84, 183, and 184 with acid results in the same transformation (Equation 4) <1982J(P1)831>. Compound 114 and the 4-chlorophenyl derivative 185 could also be protonated with perchloric acid but in this case S-dealkylation did not occur and a salt was obtained (Equation 5) <1986LA1648>. 

Similarly to the benzothiazine ylides, the salt 210 unndergoes S-dealkylation upon heating (Equation 15) <1985S688>. 

The thermal S-dealkylation of benzothiazine ylides was shown in Scheme 11 and the dealkylation of a sulfonium salt in Scheme 37. All other reported reactions involve N-substituents. 

Oxidation Carbon-Sulfur Systems. The most common metabolic process that affects a C-S system is S-oxidation. The S atom is oxidized to a sulfoxide. In the case of thioketones, the C=S double bond is converted to a C=0 bond. For thioethers, oxidative S-dealkylation is a possibility. 

R = Et) yields, by the familiar Hugershoff cyclization,114 the substituted benzthiazole 128 and not the thiadiazolidine 129. In 1,5-dialkyl-aryl group suitable for benzthiazole formation, oxidation by iodine or bromine causes mainly S-dealkylation and subsequent formation of cyclic disulfides (126)137 in two cases, however, the formation of thiadiazolines (129 R = PhCH2, R = Me, R" = Me or Et and R = CH2=CHCH2, R=p-C6H4Me, R" = Me)137-138 as additional products in undisclosed yields, has been observed. 

Dealkylation 0-, N-, and S-Dealkylation. Probably the best known example of O-dealkylation is the demethylation of p-nitroanisole. Due to the ease with which the product, /t-nilrophcnol, can be measured, it is a frequently used substrate for the demonstration of CYP activity. The reaction likely proceeds through formation of an unstable methylol intermediate (Figure 7.5). 

Finally, cytochromes P-450 catalyze the oxidation of heteroatom-con-taining molecules, leading to products that derive either from the transfer of an oxygen atom to the heteroatom (N-or S-oxygenation) or from the oxidative cleavage of a carbon-heteroatom bond (N- or S-dealkylation) [46],... 

Many xenobiotics contain alkyl groups, such as the methyl (-CH3) group, attached to atoms of O, N, and S. An important step in the metabolism of many of these compounds is replacement of alkyl groups by H, as shown in Figure 7.6. These reactions are carried out by mixed-function oxidase enzyme systems. Examples of these kinds of reactions with xenobiotics include O-dealky-lation of methoxychlor insecticides, N-dealkylation of carbary 1 insecticide, and S-dealkylation of dimethyl mercaptan. Organophosphate esters (see Chapter 18) also undergo hydrolysis, as shown in Reaction 7.3.12 for the plant systemic insecticide demeton ... 

The reactions of [WF6] with binary fluorides may be explained by the disproportionation of this ion to WF6 and WF4 followed, in some instances, by the complex-ing of the WF4 with the fluoroanion.431" WC16 or WC15 react with an excess of a dialkyl sulphide, R2S (R = Me or Et), via an S-dealkylation sequence to produce (R3S)2[WC16] 4316 Synthetic procedures suitable for the preparation of WOX2 (X = Cl or Br) have been described432 and thermochemical data have been obtained for WSF2.352... 

Whereas complexes of ethylenedithiolate H2C2S212 are typically prepared by the reductive S-dealkylation of c -H2C2(SCH2Ph)2 (Section II.B), a viable alternative route involves base hydrolysis of l,3-dithiol-2-one, H2C2S2(CO).The parent H2C2S2CO can in turn be prepared on a multigram scale from chloroacetal-dehyde (82). This l,3-dithiol-2-one can be functionalized via deprotonation followed by C-alkylation (72), thus opening the way to a variety of functional dithiolenes (Eq. 7). 

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