Electron dealkylation

In the reactions characterized in the general sense above, phenyl and benzyl were the organic residues bound to phosphorus. It is not clear which of these groups is removed in the LAH dealkylation step. It should also be noted that as tetraquaternary phosphonium salts, these species do not qualify as crown analogs in the strictest sense because of the absence of lone pair electrons on phosphorus. Furthermore, the quaternary phosphorus can resist oxidation much better than secondary or tertiary phospho-... 

Toluene (methylbenzene) is similar to benzene as a mononuclear aromatic, but it is more active due to presence of tbe electron-donating metbyl group. However, toluene is much less useful than benzene because it produces more polysubstituted products. Most of tbe toluene extracted for cbemical use is converted to benzene via dealkylation or disproportionation. Tbe rest is used to produce a limited number of petro-cbemicals. Tbe main reactions related to tbe cbemical use of toluene (other than conversion to benzene) are the oxidation of the methyl substituent and the hydrogenation of the phenyl group. Electrophilic substitution is limited to the nitration of toluene for producing mono-nitrotoluene and dinitrotoluenes. These compounds are important synthetic intermediates. 

The dealkylative functionalization of tertiary amines 23 with electron deficient heteroaryl chlorides including triazinyl chloride 24 has been published <06TL2229>. Efficient and practical reaction conditions were determinated for a range of substrates. 

In the second example, N-dealkylation, oxidation of the carbon next to the nitrogen leads to a carbinolamine. This spontaneously leads to formaldehyde and an amine. The mechanism involves loss of a proton with electrons moving toward the electronegative nitrogen atom. The negative charge on the nitrogen is neutralized due to the addition of a proton from the environment. 

FIGURE 4.51 Mechanism for cytochrome P450-catalyzed N-dealkylation via an initial single electron pathway, SET, or via the hydrogen atom abstraction pathway, HAT. 

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. 

A similar mechanism was invoked by Ohshima and Kawabata (2) to account for their results in the nitrosation of tertiary amines and amine oxides. In applying these concepts to the nitrosative dealkylation of tetraalkyltetrazenes, Michejda al. 5) introduced an interesting variant by suggesting that immonium ions could be formed in two successive one-electron oxidation steps (for example by ferric ion oxidation of tertiary amine to the radical cation followed by radical abstraction of a hydrogen atom from the alpha position), rather than exclusively through the one-step removal of a hydride ion as nitroxyl. The resulting immonium ion was again considered to react directly with nitrite to produce the N-nitroso derivative. These reactions are summarized in Fig. 2b. 

Another series of reactions (Nos 8-15) show different possibilities for the addition of conjugated double bonds on a P(III) atom. Although this type of reaction has been stated to be a concerted six-electron dissociative process, and therefore stereoselective, its scope is limited by the fact that it cannot be generalized to all P(III) compounds as some of them are fairly unreactive, or yield phosphonium salts or may even be dealkylated. 

The proton adds to the aromatic ir electron complex of o-ethyl-toluene to form a charged structure that is the same for isomerization and dealkylation. The next step depends on whether the positive charge is stabilized on the ethyl group by nearby alumina sites in the micropore or if it is dispersed over the entire molecule. Stabilization of the ethyl car-bonium ion by a negative charge from a nearby alumina tetrahedron results in a stabilized transition state that favors dealkylation. 

Cross-linked polystyrene can be acylated with aliphatic and aromatic acyl halides in the presence of A1C13 (Friedel-Crafts acylation, Table 12.1). This reaction has mainly been used for the functionalization of polystyrene-based supports, and only rarely for the modification of support-bound substrates. Electron-rich arenes (Entry 3, Table 12.1) or heteroarenes, such as indoles (Entry 5, Table 15.7), undergo smooth Friedel-Crafts acylation without severe deterioration of the support. Suitable solvents for Friedel-Crafts acylations of cross-linked polystyrene are tetrachloroethene [1], DCE [2], CS2 [3,4], nitrobenzene [5,6], and CC14 [7]. As in the bromination of polystyrene, Friedel-Crafts acylations at high temperatures (e.g. DCE, 83 °C, 15 min [2]) can lead to partial dealkylation of phenyl groups and yield a soluble polymer. 

A reaction between methoxythioanisole and metallic sodium in HMPA results in the formation of an initial anion radical. This anion radical contains an unpaired electron at the thiomethyl group. Scission of the thiomethyl group is the next step of the reaction. The product obtained is reduced no further. Such selective dealkylation proceeds according to Scheme 3-1 ... 

Reaction of 9-chloroacridine with aryl sulfonyl hydrazides results in aminodechlo-rination to give the corresponding A-acridinylbenzenesulfonyl hydrazides kinetic studies in methanol and DMSO have been reported.44 Reaction of electron-deficient heteroaryl chlorides with tertiary amines may proceed by quaternization and dealkylation, as shown in Scheme 3. These reactions occur under mild conditions, e.g. acetonitrile solvent at room temperature, and in THF may be accelerated by the addition of lithium chloride.45... 

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