Dealkylation of esters

Dealkylation of esters,1 The combination of an aluminium halide and a dialkyl sulfide is more potent than the aluminum halide ethanethiol system. Dealkylation of higher esters is possible with the newer system. The order of activity of sulfides is tetrahydrothiophene > (CH3)2S > (C2H5)2S. 

Dealkylation of esters.1 NaHSe, generated in situ from Se and NaBH4 in DMF, is effective for cleavage of esters. C6H5SeNa also effects this reaction (11, 475), but this reagent is more difficult to prepare and handle. 

Dealkylation of esters cleavage of lactones. The combination of AICI3 or AlBr3 and a thiol as the nucleophile can cleave esters in high yield under mild conditions (equation 1). The reaction is not subject to steric hindrance. Debenzylation of benzyl esters is also possible. 

We next investigated the dealkylation of S-b-tBM with TMSI. Unlike the reaction with S-b-MM, it required only 4 hr at room temperature to completely cleave the t-butyl ester. Work-up under acidic conditions gave S-b-MA which was virtually identical by NMR, IR, GPC, and titration with that just described above. Likewise, neutralization with KOH resulted in quantitative conversion to S-b-MA.K. Although the initially formed product of the reaction of alkyl esters with TMSI is presumably the trimethylsilyl ester (1 7 ), we were not able to isolate or characterize this copolymer. It is known that trimethysilyl methacrylate and its polymers spontaneously hydrolyze even in moist air (19). Any traces of water in the methanol used to precipitate the reaction mixture would thus preclude isolation of the intermediate trimethylsislyl ester. 

FIGURE 4.66 P450-catalyzed oxidative O-dealkylation of an ester. 

As in carboxylic esters it is possible to substitute alkoxy groups of Fischer-type carbene complexes by non-carbon nucleophiles, such as other alcohols [73,214,218], enols [219], aliphatic amines [43,64,66,220-224], aniline [79], imines [225], or pyrroles [226]. Strong nucleophiles can also lead to a dealkylation of methoxy-substituted carbene complexes (5 2 at the methyl group, [227]), in the same way as methyl esters can be cleaved by nucleophiles such as iodide. Carbon... 

By treatment with NaBH4 in aqueous NaOH in the presence of dithienyl ditelluride, a-phenylseleno carboxylic esters and malonates, as well as a-phenylseleno carboxylic acids, are deselenylated to the corresponding seleno-lree acids in good yields. The selective removal of the seleno group without dealkylation of the ester moiety is achieved by the methods depicted in the scheme. 

Thus the postulate that a-amino nitrite esters could form and fragment to nitrosamines has provided a useful construct for explaining some aspects of the nitrosative dealkylation of tertiary amines and their derivatives. 

The concave acids 38 and the esters 39 could be interconverted. Reaction of the acids 38 with diazomethane led to the methyl esters 39. 8 2 dealkylation of the esters 39 by lithium iodide in pyridine gave the acids 38 [27]. 

When l,l-dimethoxy-4-propyl-2,6-diphenyl-A5-phosphorin (53) is transformed into its 4-carbenium tetrafluoroborate (54) and treated with a base the 4-(l-propenyl) derivative (55) is formed. This, by a two phase oxidation with KMn04, gives the aldehyde (56) which can be further transformed, e.g. into the nitrile (57 equation 34) (75AG(E)lll). An Arbusov type dealkylation of the cation salts (49) (or 54) with LiBr gives the phosphinic ester (58 equation (35)). 

The condensation of an aldehyde, benzyl carbamate, and triphenyl phosphite, first described by Oleksyszyn et al., 25,26 affords a direct route to a-aminoalkylphosphonates 4 that are conveniently protected for subsequent reactions (Scheme 4). Since dealkylation of the quaternary phosphonium intermediate 3 is not possible in this case, formation of the pen-tavalent product 4 presumably involves activation of the solvent and formation of phenyl acetate. This method is useful for the synthesis of aliphatic and aromatic amino acid analogues. However, monomers with more elaborate side chains are often incompatible with the reaction conditions. The free amine can be liberated by treatment with HBr/AcOH or by hydrogenolysis after removal of the phenyl esters. The phosphonate moiety can be manipulated by ready exchange of the phenyl esters in alkaline MeOH and activation as described in Section 10.10.2.1.1. Related condensations with other trivalent phosphite derivatives have been reported. 27-30 ... 

Several classes of synthesized calixarenes bearing several moieties (ether, ester, and amide derivatives), were tested for the extraction of strontium picrates (from aqueous solutions into dichloromethane).128 Only a few of them show appreciable extraction levels. The p-i-butyl calix[6]arene hexa(di-/V-ethyl)amide (CA4) shows a very high extraction level of alkaline earth cations with respect to alkali metal cations. Moreover, dealkylation of the calix[6]arene hcxa(di-/V-cthyl)amidc (CA5) decreases the extraction of both sodium and strontium. As this decrease is much more important for sodium than for strontium, the Sr/Na selectivity, which increases from 3.12 to 9.4, is better than that achieved for DC18 derivative under the same conditions (8.7). These results were confirmed by extraction of strontium (5 x 10 4 M) from 1 M HN03 solutions, where it was found that p-t-butyl calix[4]arene tetra(di-N-ethyl) amide (CA2) (10 2 M in NPOE) extracts only sodium (DNa = 12.3, DSl < 0.001). 

The O -dealkylation of organophosphorus triesters differs from that of p-nitroanisole in that it involves the dealkylation of an ester rather than an ether. The reaction was... 

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 ... 

Methyl esters 333 that are activated toward decarboxylation by a C-2-ethoxycarbonyl group and tethered by an alkyl chain to an acrylate Michael-acceptor undergo chemoselective S] [2-dealkylation of the methyl ester, decarboxylation and cyclization upon exposure to lithium chloride in DMEU, affording tetrahydropyrans in excellent yield and diastereoselectivity (Equation 142) <1998JOC144>. 

The O-dealkylation of organophosphorus triesters differs from the above reactions in that it involves the dealkylation of an ester rather than an ether. The reaction was first described for the insecticide chlorfenvinphos (Figure 10.2B), but is now known to occur with a wide variety of vinyl, phenyl, phenylvinyl, and naphthyl phosphates and the thionophosphate triesters. At least one phosphonate, O-ethyl O-p-nitrophenyl phenylphosphonate (EPNO), is also metabolized by this mechanism. 

O-Dealkylation O-Dealkylation of alkyl groups of the ester or ether structures of insecticides occurs frequently, but it also involves an unstable a-hydroxy intermediate as found in N-dealkylation. For example, methoxychlor is O-demethylated by the system (Figure 8.6). O-Dealkylation is known to occur with a wide variety of organophosphates, including certain dimethyl triesters. O-Dealkylation results in detoxification. 

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