Activator-alkyl mechanism

Variations of this mechanism included the suggestion of a partially bonded alkene molecule,299 the participation of a titanium-aluminum ion pair,300 and a concerted alkene insertion.301 The development of the activator-alkyl mechanism was probably strongly influenced by the Aufbau reaction, studied originally by Ziegle.102 He observed that Group I—III alkyl compounds such as Et3Al catalyzed the oligomerization of ethylene to terminal alkenes. Additional evidence of such mechanism comes from the fact that alkylaluminum compounds exist in dimeric... 

The antitumor activity displayed by the mitosanes and many synthetic aziridines stems from their ability to act as alkylating agents which chemically modify (crosslink) DNA. For this reason, a large number have been screened for antitumor activity, the mechanism of which has been the subject of considerable research effort <75CJC289l). An excellent account of the broad spectrum of biological properties of a multitude of compounds containing the aziridinyl moiety has been published [Pg.93]

A possible mechanism proposed by Kuivila was based on the fact that retardation by hydroquinone has been observed 72) (see however 73)) and that optically active alkyl halides RX have been transformed into racemic RD 72). 

Another class of DNA alkylating agents, the Mitomycins, proved to be most promising in clinical trials. Among these, mitomycin C, shown in Fig. 6.1, exhibits significant anti-tumor activity. Its mechanism of activation consists of a complex bioreductive process. The first step is the reduction to hydroquinone, followed by a loss of methanol. This reaction fa-... 

Only scant information is available about the influence of coke formation on the alkylation mechanism. It has been proposed that, similar to the conjunct polymers in liquid acids, heavy unsaturated molecules participate in hydride transfer reactions. However, no direct evidence was given for this proposition (69). In another study, the hydride transfer from unsaturated cyclic hydrocarbons was deduced from an initiation period in the activity of NaHY zeolites complete conversion of butene was achieved only after sufficient formation of such compounds (73). 

Now let us have a fresh look at and 8, 2 mechanisms by taking examples of optically active alkyl halides. 

In case of optically active alkyl halides, the product formed as a result of Sn2 mechanism has the inverted configuration as compared to the reactant. This is because the nucleophile attaches itself on the side opposite to the one where the halogen atom is present. When (-)-2-bromooctane is allowed to react with sodium hydroxide. (+)-octan-2-ol is formed with the -OH group occupying the position opposite to what bromide had occupied. 

Scheme 6 Loss of stereoinformation during the Bi(OTf)3-catalyzed Friedel-Crafts-alkylation implies a carbocationic intermediate. Mechanism A TfOH generated in situ from Bi(OTf)3 is thought to be the catalytic active species. Mechanism B Bismuth(III) acts as a Lewis acid. TfOH only regenerates Bi(OTf)3 from its less reactive monohydroxide...

Catalyses of HY and HL are not controlled by sterlc circumstances of pore and channel. HY and HL have enough spaces for transition state to allow the formation of all IPBP Isomers. Product distribution changes markedly by increasing reaction temperature. Catalysis at low temperatures is determined by the reactivity of each position of biphenyl molecule to yield 2- and 4-IPBP as principal isomers. However, the selectivity of 3-IPBP increases extensively with decrease of 2-IPBP with rising temperature, and an equimolar mixture of 3-and 4-IPBP is produced at high temperatures. These changes in product distribution are ascribed to the isomerization of 2-IPBP to the more stable 3-IPBP by a de-alkylatlon and alkylation mechanism. Catalysis of HZSM-5 at 300°C is nonselective with low activity. The reaction occurs at external surface because the pore is too small to allow the entrance of biphenyl molecule. 

In Studying asymmetric oxidation of methyl p-tolyl sulfide, employing Ti(OPr-/)4 as catalyst and optically active alkyl hydroperoxides as oxidants, Adam and coworkers collected experimental evidence on the occurrence of the coordination of the sulfoxide to the metal center. Therefore, also in this case the incursion of the nucleophilic oxygen transfer as a mechanism can be invoked. The authors also used thianthrene 5-oxide as a mechanistic probe to prove the nucleophilic character of the oxidant. 

The mechanism of Friedel-Crafts alkylation with alkyl halides involves initial formation of the active alkylating agent, which then reacts with the aromatic ring. Depending on the catalyst, the solvent, the reaction conditions, and the alkyl halide, the formation of a polarized donor-acceptor complex or real carbocations (as either an ion pair or a free entity) may take place ... 

Carbocations contain sp hybridized orbitals and thus have planar structures. S 1 mechanisms proceed via a carbocation intermediate, so a nucleophile attack is equally possible from either side of the plane. Therefore, a pure, optically active alkyl halide undergoing an S 1 substitution reaction will generate a racemic mixture as a product, as shown in Figure 3-6. 

Among the halides that react through this process are unactivated aromatic and heteroaromatic halides, vinyl halides, activated alkyl halides [nitroalkyl, nitroallyl, nitro-benzyl and other benzylic halides substituted with electron-withdrawing groups (EWG) as well as the heterocyclic analogues of these benzylic systems] and non-activated alkyl halides that have proved to be unreactive or poorly reactive towards polar mechanisms (bicycloalkyl, neopentyl and cycloalkyl halides and perfluoroalkyl iodides). 

Br or I by NMR, conductometric, stereochemical, and kinetic studies (256). In particular, it was demonstrated that silylation of optically active alkyl thiophosphonate with a stoichiometric amount of Me3SiBr leads to racemic silyl esters and the rate of optical rotation decay is equal to the rate of silyl ester formation (256) in spite of the fact that no bond to phosphorus was cleaved. Thus, the reaction must involve an achiral transient species [Eq. (58)]. This result is also proof of fast exchange of silyl groups between the complex and the silane, which occurs via the dissociation-recombination mechanism. 

Latent forms of MMPs can be activated by mechanisms which cause the dissociation of the intramolecular complex between a particular cysteine residue and the required zinc metal ligand (a complex that blocks the active site) [47], This occurs because the cysteine of the latent enzyme is coordinated to the active site in a particular way that blocks the MMP active site. Collectively, the activation of MMPs occurs through a process which has been termed the cysteine-switch . Activators of the MMPs include proteases (e.g. plasmin), conformational perturbants (SDS, NaSCN), heavy metals and organomercurials (e.g. Au(I) compounds, Hg(II)), oxidants (e.g. OC1-), disulfide compounds (e.g. GSSG) and sulfhydryl alkylating agents (e.g. V-ethylmaleimide) [47 and refs, therein]. 

Mechanistic studies have been carried out on the oxidative addition of alkyl halides to Sn[CH(SiMe3)2]2 (79, 80). Radical intermediates were observed by spin trapping, and when an optically active alkyl halide was used racemization occurred. The evidence obtained led to the proposed mechanism shown in Eq. (40). 

Holmberg showed that optically active alkyl halides are racemized in solution at rates which are second-order mixed with respect to halide ion and alkyl halide. By using 2-octyl iodide, Hughes and coworkcrs showed that the rate of exchange with radioactive 1 in acetone solution is precisely equal to the rate of inversion, both rates being mixed second-order. This, of course, is quite reasonable on the assumption that both reactions proceed by Sn2 mechanisms with inversion of configuration ... 

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