Alkylation, mechanism

The bulk solvent effect on the reaction energy, described by the lower portion of Scheme 2.3, significantly modifies the relative importance of the uncatalyzed and water-assisted alkylation mechanism by o-QM in comparison to the gas phase. 

Depending on the nature of surface chain growth species, on the other hand, one is confronted mainly with the alkyl mechanism,6 based on the insertion of a methylene species C CHj) into the metal-alkyl bond, or with the alkenyl mechanism,2 wherein a surface vinyl species ( CH=CH2) reacts with a surface methylene ( CII2) to form an allyl species ( CH2CH=CH2). 

In the present work the unassisted CO dissociation version of the carbide theory has been adopted to describe CO conversion, while the alkyl mechanism has been adopted for describing the chain growth process. Accordingly, as proposed in our previous work,10 the FT reaction pattern has been detailed as follows ... 

A complete kinetic model of FTS over a state-of-the-art Co catalyst has been derived on the basis of the carbide theory and of CH2 insertion alkyl mechanism. 

Fig. 24 Reductive alkylation mechanism of interaction of kinamycin C with DNA as originally proposed [67], Nucleophilic (DNA) attack can occur on the Michael acceptor 32 through pathway a or b. The same mechanism should be applicable with the revised diazo structures...

Since the discovery of alkylation, the elucidation of its mechanism has attracted great interest. The early findings are associated with Schmerling (17-19), who successfully applied a carbenium ion mechanism with a set of consecutive and simultaneous reaction steps to describe the observed reaction kinetics. Later, most of the mechanistic information about sulfuric acid-catalyzed processes was provided by Albright. Much less information is available about hydrofluoric acid as catalyst. In the following, a consolidated view of the alkylation mechanism is presented. Similarities and dissimilarities between zeolites as representatives of solid acid alkylation catalysts and HF and H2S04 as liquid catalysts are highlighted. Experimental results are compared with quantum-chemical calculations of the individual reaction steps in various media. 

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). 

Fig. 7. Self-alkylation mechanism, depicted with 2-butene as the feed alkene.

Fig. 8. Concerted alkylation mechanism including alkylation, self-alkylation , cracking, dimerization, and hydride transfer via isobutane and via conjunct polymers.

The foregoing review of the alkylation mechanism and the influence of the catalyst type and reaction conditions show that, in essence, the chemistry is identical with all the examined acid catalysts, liquid and solid. Differences in the importance of individual reaction steps originate from the variety of possible structures and distributions of acid sites of solid catalysts. Changing process parameters induces similar effects with each of the catalysts however, the sensitivity to a particular parameter depends strongly on the catalyst. All the acids deactivate by the formation of unsaturated polymers, which are strongly bound to the acid. 

The intramolecular cyclization of propenyl or allylphosphonium salts [e.g. (109)] to phosphinolinium or isophosphinolinium salts [e.g. (110)] by polyphosphoric acid (PPA) has been shown109 to proceed via a cation-alkylation mechanism, as suggested in the original report.110... 

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. 

A new mechanism to interpret alkene formation in Fischer-Tropsch synthesis has been presented 499-501 There is a general agreement that hydrocarbon formation proceeds according to the modified carbene mechanism. Specifically, CO decomposes to form surface carbide and then undergoes hydrogenation to form surface methine (=CH), methylene (=CH2), methyl and, finally, methane. Linear hydrocarbons are formed in a stepwise polymerization of methylene species. When chain growth is terminated by p-hydride elimination [Eq. (3.61)], 1-alkenes may be formed,502 which is also called the alkyl mechanism ... 

However, there are certain anomalies with respect to the alkyl mechanism, namely, the relatively small amounts of C2 hydrocarbons in the Anderson-... 

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 observed effects of structure on rate and on orientation, confirmed by the Brown selectivity relationship, show that there is no basic difference between heterogeneous catalytic alkylation of aromatic compounds and homogeneous electrophilic aromatic substitution, cf. nitration, sul-phonation etc. This agreement allows the formulation of the alkylation mechanism as an electrophilic attack by carbonium ion-like species formed on the surface from the alkene on Br0nsted acidic sites. The state of the aromatic compound attacked is not clear it may react directly from the gas phase (Rideal mechanism ) [348] or be adsorbed weakly on the surface [359]. 

The intermediate tertiary carbinol could not be detected (with the exception of bis(trifluoromethyl)(hydroxyphenyl)carbinol from hexafluoro-acetone and phenol [395]) and reacts readily with another molecule of phenol this second stage of the reaction is, in fact, an alkylation of phenol by the tertiary carbinol, or by the carbonium ion formed from it, by a common carbonium ion alkylation mechanism (Sect. 3.3). 

Bizelesin (6.e) is a minor groove binding bis-alkylator. Like almost all DNA alkylators, bizelesin alkylates through a reactive intermediate and not through a simple, one-step SN2 pathway. Propose an alkylation mechanism for bizelesin. (Hint Consider adozelesin (6.44).) (Pitot, H. C., Reid, J. M., Sloan, J. A., Ames, M. M., Adjei, A. A., Rubin, J., et al. A Phase I Study of Bizelesin [NSC 615291] in Patients with Advanced Solid Tumors. Clin. Cancer Res. 2002, 8, 712-717.)... 

Eder E, Henschler D, Neudecker T. 1982. Mutagenic Properties of allylic and a,(3-unsaturated compounds consideration of alkylating mechanisms. Xenobiotica 12 831-848. 

Chloroxymorphamine (/3-COA), 191 (R = Me), on the other hand, produced irreversible agonist responses(307) also, presumably by an alkylating mechanism. Alkylation probably occurs from attack by a receptor nucleophilic group upon a mediating aziridinium ion. The mutagenic nature of compounds capable of generating aziridinium ions is likely to render compounds of this sort unacceptable for human therapy. 

The two most relevant mechanisms of chain growth via "Ci" species that we compare are the Brady-Pettit alkyl mechanism (34,35) and the Gaube-Maitlis alkylidene/alkenyl (36,37) chain-growth mechanism. 

Since alkylate compositions from the four butene isomers are basically similar, the butenes are thought to isomerize considerably, approaching equilibrium composition prior to isobutane alkylation. Such a postulation is at variance v/ith previously published alkylation mechanisms. The Isomerization step yields predominantly isobutene which then polymerizes and forms a 2,2,4-trimethylpentyl carbonium ion, a precursor of 2,2,4-trimethylpentane, the principal end product. The 2,2,4-trimethylpentyl ion is also capable of isomerization to other trimethylpentyl ions and thus yields other trimethylpentanes, principally 2,3,4-trimethyl-pentane and 2, 3, 3-trimethylpentane. 

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