Demethylation examples

Microbial biomethylation, antimony, 12, 644 Microbial dealkylation, examples, 12, 610 Microbial demethylation, examples, 12, 610 Micro-emulsion techniques, for molecular precursor transformations, 12, 46 Microencapsulation... 

Another important use of BCl is as a Ftiedel-Crafts catalyst ia various polymerisation, alkylation, and acylation reactions, and ia other organic syntheses (see Friedel-Crafts reaction). Examples include conversion of cyclophosphasenes to polymers (81,82) polymerisation of olefins such as ethylene (75,83—88) graft polymerisation of vinyl chloride and isobutylene (89) stereospecific polymerisation of propylene (90) copolymerisation of isobutylene and styrene (91,92), and other unsaturated aromatics with maleic anhydride (93) polymerisation of norhornene (94), butadiene (95) preparation of electrically conducting epoxy resins (96), and polymers containing B and N (97) and selective demethylation of methoxy groups ortho to OH groups (98). 

Halide ions may attack 5-substituted thiiranium ions at three sites the sulfur atom (Section 5.06.3.4.5), a ring carbon atom or an 5-alkyl carbon atom. In the highly sterically hindered salt (46) attack occurs only on sulfur (Scheme 62) or the S-methyl group (Scheme 89). The demethylation of (46) by bromide and chloride ion is the only example of attack on the carbon atom of the sulfur substituent in any thiiranium salt (78CC630). Iodide and fluoride ion (the latter in the presence of a crown ether) prefer to attack the sulfur atom of (46). cis-l-Methyl-2,3-di-t-butylthiiranium fluorosulfonate, despite being somewhat hindered, nevertheless is attacked at a ring carbon atom by chloride and bromide ions. The trans isomer could not be prepared its behavior to nucleophiles is therefore unknown (74JA3146). 

In the example below, Bhardwaj and coworkers synthesized tetramethoxyflavone 36 this flavonol was believed to be the structure of a compound isolated from Artemisia annua Methyl ketone 37 and aldehyde 38 were smoothly condensed to afford chalcone 39 in 73% yield. 39 was then converted to 40 under slightly modified AFO conditions in low yield. Selective demethylation of 40 gave 36. However, spectral data and melting point data of 36 did not match up with the compound isolated from the plant. Hence, the original structure was misassigned and was not flavonol 36. 

Scheme 5.1-4 Two examples of aryl demethylation reactions followed by cyclization.

Another instructive example is provided by a series of a-phenyl-a,P-dibromo-phosphonates 170, 171, 172. While the phosphonate dianion 170 fragments instantaneously at room temperature with formation of the POf ion (see also Sect. 4.1.3), the analogous reaction of the phosphonic monoester anion 171 leading to methyl metaphosphate 151 requires more drastic conditions and is at least 1000 times slower the diester 172 is essentially stable under the reaction conditions described for 171 addition of triethylamine leads to slow demethylation H0). The behavior of 171 contrasts with that of simple (3-haloalkylphosphonic monoesters which merely eliminate HHal on treatment with bases94. Thus it is the possibility of formation of a phenyl-conjugated double bond which supports the fragmentation of 171 to olefin + 151. 

Two new polycyclic pyridoacridine alkaloids, arnoamine B, 289, and its demethylated analogue, arnoamine A, have been isolated from the ascidian Cystodytes sp. These new compounds are the first known examples of pyrroles fused to pyridoacridines, have antifungal properties, and are cytotoxic in several human tumor cell lines <1998JOC1657>. Both these compounds have been synthesized, starting from the hydrazone 290 with a Fischer indole synthesis (Scheme 73) <2000JOC5476>. 

Selective de-ethylation of 2-ethoxyanisole is observed using KOtBu as the reagent in the presence of 18-crown-6 as the phase transfer agent (PTA). With the addition of ethylene glycol (E.G.), the selectivity is reversed and demethylation occurs (Eq. (33) and Tab. 3.13). If the involvement of microwaves is favorable in both examples, the second reaction should be more strongly accelerated than the first [87]. 

The microwave-specific effect is more apparent in the case of demethylation (Sn2). The microwave acceleration clearly is more pronounced with the difficulty of the reaction, thus constituting a clear example of an increased microwave effect with a more difficult reaction, indicative of a later TS position along the reaction coordinate. The microwave effect may also be connected to the more localized charge in the Sn2 transition state (three centers) when compared to that of p-E2 (charge developed over five centers). 

In the case of the most reactive compounds, substitution at the carbon atom of diselenonium and ditelluronium dications is also a possible pathway. For example, formation of diselenide 117 from selenoxide 115 was explained by demethylation of intermediate dication 116 with trifluoroacetate anion.126 Dealkylation of salt 118, which is stable up to —20°C, leads to formation of nitrilium salt 119. The latter is transformed to amide 120 upon hydrolysis.64 Dealkylation of intermediate diselenonium dication 122 was suggested as the key step in the oxidative synthesis of 1,2,4-diselenazolidines 123 from eight-membered heterocycles 121 (Scheme 46).127... 

One of numerous examples of LOX-catalyzed cooxidation reactions is the oxidation and demethylation of amino derivatives of aromatic compounds. Oxidation of such compounds as 4-aminobiphenyl, a component of tobacco smoke, phenothiazine tranquillizers, and others is supposed to be the origin of their damaging effects including reproductive toxicity. Thus, LOX-catalyzed cooxidation of phenothiazine derivatives with hydrogen peroxide resulted in the formation of cation radicals [40]. Soybean LOX and human term placenta LOX catalyzed the free radical-mediated cooxidation of 4-aminobiphenyl to toxic intermediates [41]. It has been suggested that demethylation of aminopyrine by soybean LOX is mediated by the cation radicals and neutral radicals [42]. Similarly, soybean and human term placenta LOXs catalyzed N-demethylation of phenothiazines [43] and derivatives of A,A-dimethylaniline [44] and the formation of glutathione conjugate from ethacrynic acid and p-aminophenol [45,46],... 

And finally, additional research is needed on mercury accumulation and detoxification in comparatively pristine ecosystems. Key uncertainties in understanding the process of mercury uptake in aquatic ecosystems, for example, include relations between water chemistry and respiratory uptake, quantitative estimates of intestinal tract methylation and depuration, and degree of seasonal variability in mercury speciation and methylation-demethylation processes (Post et al. 1996). 

Many of the premetallised direct dyes are symmetrical structures in the form of bis-1 1 complexes with two copper(II) ions per disazo dye molecule. Scheme 5.12 illustrates conversion of the important unmetallised royal blue Cl Direct Blue 15 (5.43), derived from tetrazotised dianisidine coupled with two moles of H acid, to its much greener copper-complex Blue 218 (5.44) with demethylation of the methoxy groups as described above. Important symmetrical red disazo structures of high light fastness, such as Cl Direct Red 83 (5.45), contain two J acid residues linked via their imino groups. Unsymmetrical disazo blues derived from dianisidine often contain a J acid residue as one ligand and a different coupler as the other, such as Oxy Koch acid in Cl Direct Blue 77 (5.46), for example. 

N-demethylation at the three N-methyl sites. In this regard, the 3-N-demethylation of caffeine to generate paraxanthine can serve as a particularly good in vivo indicator of the presence and activity of CYP1A2 (Fig. 4.7). In the case of phenacetin, CYP1A2 catalyzes N-deethylation to generate acetaminophen. Not unexpectedly, 1 A2 s selectivity toward heterocyclic aromatic substrates carries over to inhibitors of the enzyme. Furafylline (Fig. 4.7) is an example of a particularly potent 1A2 mechanism-based inhibitor. 

Our next examples concern ring-substituted succinimides. 2-Phenylsuc-cinimide (4.185), the A-demethylated metabolite of the antiepileptic drug phensuximide, was found to be a better substrate of DHPase than succinimide itself. Two ring-opened metabolites are conceivable, 3-phenylsuccin-amic acid (4.186) and 2-phenylsuccinamic acid (4.187), but only the latter was formed enzymatically. 2-Phenylsuccinimide is chiral, and ring-opening... 

V-Subslilulion and 5,5-disubstitution prevent ring opening as demonstrated by various examples. Ethotoin (3-ethyl-5-phenylhydantoin, 4.230), in contrast to its /V-dcclhylalcd metabolite, was not detectably hydrolyzed by DHPase. No ring-opened metabolite was found for phenytoin (5,5-diphenyl-hydantoin, 4.231) or nirvanol (5-ethyl-5-phenylhydantoin, 4.232), which is the AT-demethylated metabolite of mephenytoin (4.233) [144],... 

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