Alkylation proton transfer reaction

Sn2 reactions can be thought of as alkyl transfer reactions, and Sn2 characteristics can be anticipated by examining analogous proton transfer reactions. 

Quantum chemical DFT calculations at the B3LYP/6-31G(d) level have been used to study the enantioselective lithiation/deprotonation of O -alkyl and O-alk-2-enyl carbamates in the presence of (—)-sparteine and (—)-(f )-isosparteine.7 Complete geometry optimization of the precomplexes consisting of the carbamate, the chiral ligand, and the base (/-PrLi), for the transition states of the proton-transfer reaction, and for the resulting lithio carbamates have been performed in order to quantify activation barriers and reaction energies. 

Metal enolate solutions consist of molecular aggregates (6) such as dimers, trimers and tetramers in equilibrium with monomeric covalently bonded species (7), contact ion pairs (8) and solvent-separated ion pairs (9), as shown in Scheme 1. The nature of the metal cation, the solvent and, to a degree, the structure of the enolate anion itself may significantly influence the extent of association between the anion and the metal cation. In general, the factors that favor loose association, e.g. solvent-separated ion pairs, lead to an increase in the nucleophilicity of the enolate toward alkylating agents and also its ability to function as a base, i.e. to participate in proton transfer reactions. 

Enolate equilibration and di- and poly-alkylation are the major side reactions, which lead to reduced yields of desired products in ketone alkylations. These processes occur as a result of equilibration of the starting enolate (or enolate mixture) with the neutral monoalkylation product(s) via proton transfer reactions. Polyalkylation may also occur when bases, in addition to the starting enolate, which are capable of deprotonating the monoalkylated ketone are present in the medium. With symmetrical ketones, e.g. cyclopentanone and cyclohexanone, the problem of regioselectivity does not arise. However, except under special conditions, polyalkylation occurs to a significant extent during enolate alkylations of more kinetically acidic ketones such as cyclobutanone, cyclopentanone and acyclic ketones, particularly methyl ketones. Polyalkylation is also a troublesome side reaction with less acidic ketones such as cyclohexanone. 

R,2S)-Ephedrine has found most application, e.g., as a catalyst in photochemical proton transfer reactions (Section D.2.1.). and as its lithium salt in enantioselective deprotonations (Section D.2.1.). The amino function readily forms chiral amides with carboxylic acids and enamines with carbonyl compounds these reagents perform stereoselective carbanionic reactions, such as Michael additions (Sections D.1.5.2.1. and D. 1.5.2.4.), and alkylations (Section D.1.1.1.3.1.). They have also been used to obtain chiral alkenes for [1 +2] cycloadditions (Section D. 1.6.1.5.). 

When isobutane was alkylated with 1- or 2-butene in the presence of aluminum chloride monomethanolate, very little or no n-butane was formed despite the fact that appreciable amounts of 2,2,4-trimethylpentane were produced (Schmerling, 14d). Similarly, no n-butane or n-pentane, respectively, was obtained by the alkylation of isobutane with 2-butenc and with 2-pentene in the presence of sulfuric acid although trimethylpentanes were formed in both cases (McAllister et al., 12 cf. Marschner and Carmody, 24). This apparent discrepancy in the alkylation mechanism may be explained readily. The n-alkylcne is converted not into n-alkane, but into isoalkane. The resulting isobutane cannot, of course, be differentiated from that charged the resulting isopentane, on the other hand, can be and was actually found in substantial yield. In other words, the proton transfer reaction is accompanied by rearrangement of the carbon skeleton of the carbonium ion. 

The substitution of the alkyl groups in amines by silyl groups decreases their proton affinity [6] and, as a result, the proton transfer reactions from the methyl cation are less competitive with condensation. Indeed, the probability of proton transfer decreases in going from diisobutylamine to isobutylaminotrimethylsilane. However, in the case of hexamethyldisilazane this rule is broken. 

When ethyl bromide reacts with ammonia, for example, the ethylaminium bromide that is produced initially can react with ammonia to liberate ethylamine. Ethylamine can then compete with ammonia and react with ethyl bromide to give diethylaminium bromide. Repetitions of alkylation and proton transfer reactions ultimately produce some tertiary amines and even some quaternary ammonium salts if the alkyl halide is present in excess. 

The final product from such a series of nucleophilic substitution and proton transfer reactions is a tetraalkylammonium halide. TTie relative proportions of the various alkylation products depend on the ratio of alkyl halide to ammonia in the reaction mixture. V atever the starting mixture, however, the product is almost invariably a mixture of alkylated products. For this reason, alkylation of ammonia or amines is not... 

The reaction corresponds to a proton transfer and not to a net formation of ions, and thus the AS is of minor importance in the whole series, especially for the two t-Bu derivatives. This last effect is believed to be due to a structure-promoting effect of the bulky alkyl groups in the disordered region outside the primary hydration sphere of the thiazolium ion (322). 

We can extend the general principles of electrophilic addition to acid catalyzed hydration In the first step of the mechanism shown m Figure 6 9 proton transfer to 2 methylpropene forms tert butyl cation This is followed m step 2 by reaction of the car bocation with a molecule of water acting as a nucleophile The aUcyloxomum ion formed m this step is simply the conjugate acid of tert butyl alcohol Deprotonation of the alkyl oxonium ion m step 3 yields the alcohol and regenerates the acid catalyst... 

One common kind of reaction involves proton transfer occurring as a rapid equilibrium preceding the rate-determining step, for example, in the reaction of an alcohol with hydrobromic acid to give an alkyl bromide ... 

The Zincke reaction is an overall amine exchange process that converts N- 2,A-dinitrophenyl)pyridinium salts (e.g, 1), known as Zincke salts, to iV-aryl or iV-alkyl pyridiniums 2 upon treatment with the appropriate aniline or alkyl amine. The Zincke salts are produced by reaction of pyridine or its derivatives with 2,4-dinitrochlorobenzene. This venerable reaction, first reported in 1904 and independently explored by Konig, proceeds via nucleophilic addition, ring opening, amine exchange, and electrocyclic reclosure, a sequence that also requires a series of proton transfers. By... 

A detailed mechanism of Goldschmidt s process has not been given two reaction paths are possible either proton transfer to the acid with the formation of RC(OH) (in which case the slow step would be an Aac2 Ingold mechanism) or nucleophilic attack of the carbonyl group of the acid on the protonated alcohol. The second mechanism would require an alkyl scission (A l). In more recent studies2501, it has been shown that scission in most cases is of the acyl type and particularly in the examples studied by Goldschmidt. 

A low ion pair yield of products resulting from hydride transfer reactions is also noted when the additive molecules are unsaturated. Table I indicates, however, that hydride transfer reactions between alkyl ions and olefins do occur to some extent. The reduced yield can be accounted for by the occurrence of two additional reactions between alkyl ions and unsaturated hydrocarbon molecules—namely, proton transfer and condensation reactions, both of which will be discussed later. The total reaction rate of an ion with an olefin is much higher than reaction with a saturated molecule of comparable size. For example, the propyl ion reacts with cyclopentene and cyclohexene at rates which are, respectively, 3.05 and 3.07 times greater than the rate of hydride transfer with cyclobutane. This observation can probably be accounted for by a higher collision cross-section and /or a transmission coefficient for reaction which is close to unity. 

The relative probabilities of Reactions 24, 25, and 26 were, respectively, 1.00, 0.25, and 0.12 at a hydrogen pressure of about 1 atmosphere (9). These numbers could be derived either by analyzing the stable alkanes formed in the unimolecular decompositions (Reactions 24-26) or from the products of the hydride transfer reactions between C5Hi2 and the alkyl ions. Elimination of H2 from protonated pentane may also occur, but it is difficult (although not impossible) to establish this reaction through neutral product analysis. 

The principles outlined above are, of course, important in electro-synthetic reactions. The pH of the electrolysis medium, however, also affects the occurrence and rate of proton transfers which follow the primary electron transfer and hence determine the stability of electrode intermediates to chemical reactions of further oxidation or reduction. These factors are well illustrated by the reduction at a mercury cathode of aryl alkyl ketones (Zuman et al., 1968). In acidic solution the ketone is protonated and reduces readily to a radical which may be reduced further only at more negative potentials. 

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