Dealkylation reactions

The design of these distillation systems and the operating conditions used depend on the physical properties of the alkylphenols involved and on the product requirements. Essentially all alkylphenol distillation systems operate under vacuum, but the actual pressures maintained vary considerably. Vacuum operation allows reasonable reboder temperatures (200—350°C) so that thermal dealkylation reactions of the alkylphenols are slow. 

Deall lation. Chloroformates such as vinyl chloroformates (40) are used to dealkylate tertiary amines. Chloroformates are superior to the typical Von Braun reagent, cyanogen bromide, because of increased selectivity producing cleaner products. Other chloroformates such as aHyl, methyl, phenyl, and trichloroethyl have also been used in dealkylation reactions. Although the dealkylation reaction using chloroformates is mostiy carried out on tertiary amines, dealkylation of oxygen or sulfur centers, ie, ethers or thioethers, can also be achieved. a-Chloroethyl chloroformate [50893-53-3] (ACE-Cl) (41,42) is superior to all previously used chloroformates for the dealkylation reaction. ACE-Cl has the advantage that the conditions requked for ACE... 

In an attempt to study the behavior and chemistry of coal in ionic liquids, 1,2-diphenylethane was chosen as a model compound and its reaction in acidic pyri-dinium chloroaluminate(III) melts ([PyHjCl/AlCb was investigated [69]. At 40 °C, 1,2-diphenylethane undergoes a series of alkylation and dealkylation reactions to give a mixture of products. Some of the products are shown in Scheme 5.1-40. Newman also investigated the reactions of 1,2-diphenylethane with acylating agents such as acetyl chloride or acetic anhydride in the pyridinium ionic liquid [70] and with alcohols such as isopropanol [71]. 

It is also well known that alkyl groups can be tran.sferred intramolecularly from one position to another on the same ring and intermoiccularly from one aromatic ring to another through dealkylation reactions catalyzed by Lewis acid. The intramolecular alkyl-transfer is called reorientation or isomerization and the intermolecular alkyl transfer is referred to as disproportionation. Reorientation processes arc normally faster than disproportionation. 

During a study of these complexes, Treichel and Hess 145, 147) heated [Pt(PPh3)2(CNCH3)Cl]Cl, expecting to obtain Pt(PPh3)(CNCHj)Cl2 instead a novel dealkylation reaction occurred. This was extended to other related species [Eq. (36)]. Remarkably, very few examples of such reactions... 

Upon recrystallization, [Ni(tpzlmtacn)]2+ affords [Ni(L)(MeCN)]2+ (L = l,4-bis(pyrazol-l-ylmethyl)-l,4,7-triazacyclononane) via a N-dealkylation reaction and loss of a pendent arm.1420 More rational routes to Ni complexes of tacn ligands with only one or two pendent arms have been developed.1431,1432 In [Ni(L)(X) ]x (e.g., L= l-(3-aminopropyl)-l,4,7-triazacyclononane (n = 2) or l-(l-methylimidazol-2-ylmethyl)-l,4,7-triazacyclononane (n = 2) or l,4-bis(l-methyl-imidazol-2-ylmethyl)-l,4,7-triazacyclononane (n = 1), the coordination sphere is completed by additional ligands that bind either terminal (X = C1 , H20) or bridge two metal ions (X = N3 , OH, oxalate). The Ni11 complex of l,4-bis(2-pyridylmethyl)-l,4,7-triazacyclononane has been shown to be extremely inert to ligand dissociation in aqueous solution.1433 In (562), the tacn ligand provides a single bidentate arm.1434... 

We found that dichloro diorgano silanes are suitable reagents for the synthesis of diorgano bis(0-alkyl)phosphonates. A different reactivity of both chlorine atoms of the silanes is observed in the dealkylation reaction of dialkylphosphonates in contrast to Me3SiBr [2]. 

Debenzylation of 165 (R = Bn) was carried out by treatment with A1G13 affording 165 (R = H) in 80% yield <2002JME3337>. Other dealkylation reactions were carried out in the presence of sulfuric acid <1997PHA279, 2004JME2659> or triflic acid <2002TL1005, 2003JOC489>. 

The product distribution determined for the reactions performed over a broad temperature range (from -176 to 199 °C) under microwave heating was always more or less different from that obtained by conventional method. Thus, a vigorous formation of isobutene under reflux using microwave heating indicates superheating of the catalyst to a higher temperature. This facilitates the dealkylation reaction, which is promoted by elevated temperature. 

Chau and coworkers133 investigated the bioaccumulation of alkyllead compounds from water and from contaminated sediments by freshwater mussels, Elliptio complanata. Higher levels of trimethyllead than triethyllead species were accumulated after the same exposure period. In vivo transformation of the trialkyllead species by a series of dealkylation reactions giving dialkyllead and inorganic lead(II) species appears to take place. Rates of accumulation are higher for the more contaminated sediments133. 

Reaction (F) represents one of the uses of methanol (reaction (C)), and is also an example in which reaction selectivity is an important issue. The reaction cannot be allowed to go to ultimate completion, since the complete oxidation of CH3OH would lead to C02 and HzO as products. Similarly, in reaction (D), benzene and other (unwanted) products are produced by dealkylation reactions. 

Scheme 23. O-Dealkylation reactions of apoiphines by Cunninghamella elegans ATCC 9245.

N-Dealkylation reactions are not restricted to tertiary amines. Secondary amines as well as primary amines can also be dealkylated although both types are less favored than tertiary amines. In the case of primary amines, the lone pair of electrons of the amino group can interact and complex with the Fe3+ of heme. Thus primary amines tend to be inhibitors of P450 activation and for that reason are generally poor substrates. Secondary amines have metabolic properties intermediary between those of tertiary amines and primary amines. They are less-effective inhibitors because of increased steric hindrance to complex formation but are also better substrates because they are less-effective inhibitors and thereby increase the effective concentration of enzyme. 

By analogy to N- and O-dealkylation reactions, one might expect esters and amides to be susceptible to P450-catalyzed oxidative attack at the a-carbon to oxygen (esters) or a to nitrogen (amides). This is indeed the case and was first established (132) by demonstration that the pyridine diester (Fig. 4.66) was oxidatively cleaved by rat-liver microsomes to yield the monoacid as shown. 

These and other interesting results allow quantitative insight into the rate of breakdown of N-(hydroxymethyl) compounds (i.e., carbinolamines (hemi-aminals)), the reaction mechanisms of which we examined in Sect. 8.7.3 (see, in particular, Fig. 8.20) [80 - 82], These carbinolamines, we recall, are major metabolic intermediates in oxidative N-dealkylation reactions resulting from cytochrome P450 catalyzed hydroxylation of the C-atom adjacent to the... 

In some applications, it is desirable to convert EB to benzene. Dealkylation reactions are described in the next section. 

Nitrosamine formation is not the only conceivable fragmentation mechanism for compounds of structure I. By analogy to the nitrosative dealkylation reactions discussed above, one might predict that such compounds could also undergo cis elimination of nitroxyl in amide-forming reactions. Such a transformation has possibly been observed (14). During an attempt to synthesize the nitrosamino aldehyde VIII from immonium ion IX, Hecht coworkers were able to isolate only 5-10% of the desired product. The major product proved to be N-methyl-2-pyrrolidone, as shown in Fig. 10. We interpret this as evidence that an intermediate such as li can fragment not only by the Fig. 1... 

A number of examples of the use of molten pyridinium chloride (mp 144 °C) in chemical synthesis are known, dating back to the 1940 s. Pyridinium chloride can act both as an acid and as a nucleophilic source of chloride. These properties are exploited in the dealkylation reactions of aromatic ethers [4]. An example involving the reaction of 2-methoxynaphthalene is given in Scheme 5.1-2 [16,18], and a mechanistic explanation in Scheme 5.1-3 [18]. 

Buspirone is rapidly absorbed orally but undergoes extensive first-pass metabolism via hydroxylation and dealkylation reactions to form several active metabolites. The major metabolite is l-(2-pyrimidyl)-piperazine (1-PP), which has K2-adrenoceptor-blocking actions and which enters the central nervous system to reach higher levels than the parent drug. It is not known what role (if any) 1-PP plays in the central actions of buspirone. The elimination half-life of buspirone is 2-4 hours, and liver dysfunction may slow its clearance. Rifampin, an inducer of cytochrome P450, decreases the half-life of buspirone inhibitors of CYP3A4 (eg, erythromycin, ketoconazole, grapefruit juice, nefazodone) can markedly increase its plasma levels. 

Benzodiazepines undergo extensive and complex metabolism. They are excreted mainly in the urine, largely in the form of several metabolites. Biotransformation processes include mainly hydroxylation and A-dealkylation reactions, whereas the end-products include both free and conjugated compounds (116). Chlordiazepoxide, for example, is metabolized to oxazepam and other metabolites and, depending on its dosage, urine may contain significant concentrations of oxazepam (117). 

Elguero and Espada29S have used this dealkylation reaction with quaternary salts of heterocyclic compounds. Another application is the preparation of tertiary amines functionalized in the <5 position.296 In these reactions, the ammonium salt 196 is both the catalyst and the reagent. 

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