A-monodealkylation

N - Benzyl- N -p icolinoylpiperazine (EGYT-475, 4.88), a compound with potential antidepressant activity, underwent similar hydrolysis. After intravenous administration, picolinic acid (4.89) was one of its major urinary metabolites in rats the other product, A-benzylpiperazine (4.90) was also detected, but at much lower levels, since it was further transformed by A-de-benzylation [55], Since the products of direct hydrolysis of these cyclic tertiary amides (i.e., the corresponding secondary amines) were found at substantial levels, it appears that oxidative A-monodealkylation is not an essential step for hydrolysis in these compounds, in contrast to the findings for A,A-diethylbenzamide. This contradicts the hypothesis [52] (see above) that the steric bulk of the tertiary amide group impedes direct hydrolysis. Here, although the degree of steric bulk is at least comparable, direct hydrolysis clearly takes place. 

On reaction with triflic anhydride, the mono oxides of 2,2 -bis(alkylthio)biphenyl are converted into a dithiadication (48) which spontaneously monodealkylates to give a thiasulfonium salt (49) <96TL667>. 

A study was designed to define the relative rates of dealkylation of selected triazine herbicides and two monodealkylated triazine degradation products in the unsaturated zone and in surface runoff. Atrazine and propazine degrade to DEA by deethylation and deisopropylation, respectively. Similarly, atrazine and simazine can both dealkylate to DIA by removal of an isopropyl and ethyl side chain, respectively (Figure 30.12). Differences in the concentration of the dealkylated degradation product from the two different sources should indicate any preferential removal of ethyl versus isopropyl side chain. Furthermore, because monodealkylated DEA and DIA have different side chains remaining, their relative rate of removal should provide additional information on the liability of the ethyl side chain versus an isopropyl side chain. 

This study showed that under field conditions, the removal of an ethyl side chain from atrazine occurred more readily than the removal of an isopropyl side chain. Furthermore, deethylation rates of atrazine and simazine were comparable, and approximately two to three times more rapid than the rates of deisopropylation from atrazine and propazine, regardless of parent triazine. Continued dealkylation of the monodealkylated degradation products at 1 m in the unsaturated zone also shows a preferential removal of ethyl side chains over isopropyl side chains. Therefore, the small concentrations of DIA commonly reported in the environment do not result purely from a smaller production of the degradation product, but from a rapid removal once produced. This substantial turnover rate or flux of DIA in the environment is evidence for the presence of a didealkylated degradation product in the unsaturated zone (Mills and Thurman, 1994 Thurman et al., 1994). 

Maturano, M. D., Bongibault, V., Klaebe, A., and Fournier, D. (1997) A chemical model for the enzymic monodealkylation of (methyl and ethyl) parathion by glutathione-S-transferase, Tetrahedron 53, 17241-... 

Dealkylation of phosphonates. Vigorous acid treatment is usually required for this reaction. To circumvent this difficulty, both bromo- and chloro-trimethylsilane have been used with limited success. lodotrimethylsilane is more selective the parent phosphonic acids can be obtained under very mild conditions without modification of a variety of other functional groups. However, monodealkylation is not practical with this reagent. Aryl esters are not cleaved hence selective dealkylation of alkyl aryl esters of phosphonic acids may be possible. 

Krawczyk, H., A convenient route for monodealkylation of diethyl phosphonates, Synth. Commun., 27, 3151, 1997. 

The ageing process consists of the monodealkylation of the AChE-nerve agent complex. The loss of an alkyl group produces a conformational change that results in the formation of a very stable agent-enzyme complex which is then resistant to spontaneous hydrolysis and reactivation by oximes. The rate of ageing is dependent... 

By contrast, 2,3,4-tris(2-ethylhexyloxy)benzaldehyde in 1,2-dichloroethane was monodealkylated selectively at the 2-position by the dropwise addition over 30 mins, of titanium tetrachloride at 8-12°C with continued stirring for a further 30 mins, and then at ambient temperature for 2 hours prior to quenching with dilute hydrochloric acid to afford 2-hydroxy-3,4-bis(2-ethylhexyloxy)benzaldehyde in 73% yield (ref.24). 

Rapid monodealkylation was observed during A"-Fmoc deprotection of methyl- and benzyl-protected phosphates by the customary piperidine-DMF solution treatment [103,108]. Although this side reaction does not seem to compromise peptide purity, it could be decreased but not completely suppressed by employing the nonnucleophilic base 1,8-diazabicy-... 

Oximes, which are valuable intermediates for the conversion of oxoalkyl phosphonic diesters into those of aminoalkylphosphonic acids (Chapter 4, Section IV.C. 1. d), are also readily available, although it is necessary to prepare them with some care. Nevertheless, the feature of interest here is their ready degradability, particularly under aqueous conditions, and which has been intensively investigated by Breuer and coworkers. The necessity for care in the preparation of oximes of acylphosphonic diesters, is illustrated by the synthesis of dimethyl [a-(hydroxyimino)benzyl]phosphonate this compound exists in the thermodynamically more stable ( ) form which, under the influence of acid is converted into the less stable (Z) form, and both forms have been separately characterized by X-ray crystallography. The geometric isomers of the oxime differ in their behaviour under basic conditions with NaOH-MeOH, the ( ) form undergoes monodealkylation, whereas the (Z) isomer decomposes to dimethyl phosphate and benzonitrile. In aqueous solution, ( )-[a-(hydroxyimino)benzyl]phosphonic acid also decomposes into benzonitrile together with phosphoric acid, in a manner which is pH dependent, and consistent with a dissociative mechanism that involves the early formation of monomeric metaphosphate. ... 

Dealcoholation 16, 945 Dealkylation (s. a. Elimination of alkyl groups. Monodealkylation)... 

Dealkylation (s. a. Elimination of alkyl groups. Monodealkylation, Replacement of alkyl groups by hydrogen) G-Dealkylation, quinoline ring with — 12, 948 N-Dealkylation (s. a. N-De-methylation) 14, 50, 54, 769 0-Dealkylation (s. a. Ethers, cleavage)... 

N-Dealkylation also plays a role in the metabolism and selectivity of 5-triazine herbicides such as atrazine," simazine, simetryn, and ter-butryn. In species in which this pathway was prominent, the major products identified were monodealkylated triazines, which retained phytotoxicity. However, in a study of atrazine metabolism in C. album, C. strictum, and Amaranthus ponelli, Khan et al. identified the bound residue from resistant biotypes as N-desethylatrazine and suggested that sequestration of ph3 otoxic metabolites contributed to tolerance to the herbicide. " ... 

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