Acid-catalyzed dehydration, pathways

In the acid catalyzed dehydration of 2 methyl 1 propanol what carbocation would be formed if a hydride shift accompanied cleavage of the carbon-oxygen bond in the alkyloxonium lon" What ion would be formed as a result of a methyl shift" Which pathway do you think will predominate a hydnde shift or a methyl shift" ... 

An important principle, called microscopic reversibility, connects the mechanisms of the forward and reverse reactions. It states that in any equilibrium, the sequence of intermediates and transition states encountered as reactants proceed to products in one direction must also be encountered, and in precisely the reverse order, in the opposite direction. Just as the reaction is reversible with respect to reactants and products, so each tiny increment of progress along the mechanistic pathway is reversible. Once we know the mechanism for the forward reaction, we also know the intermediates and transition states for its reverse. In particular, the three-step mechanism for the acid-catalyzed hydration of 2-methylpropene shown in Mechanism 6.3 is the reverse of that for the acid-catalyzed dehydration of tert-huiy alcohol in Mechanism 5.1. 

The concerted E2 process in Figure 10.44 seems not to apply to benzylic or 3° (alkyl) alcohols, which can react by an El pathway, but the situation for 2° alcohols in aqueous solution is less certain. Lomas studied the acid-catalyzed dehydration of l,l -diadamantylethanol (25) to l,l-bis(l-adamantyl)ethene (26) in anhydrous acetic acid solution. ° Dehydration of the trideuterio-methyl analog produced a deuterium kinetic isotope effect, with ku/ku equal to 1.32. This result is not consistent with a mechanism in which the /S-proton is lost in the rate-limiting step, but it is consistent with rate-limiting formation of the carbocation intermediate (with the h/ d ratio reflecting a secondary kinetic isotope effect), as shown in equation 10.54. 

Whereas the C2—C4 alcohols are not carboxylated under the usual Koch-Haaf conditions, carboxylation can be achieved in the HF-SbF5 superacid system under extremely mild conditions.400 Moreover, Olah and co-workers401 have shown that even methyl alcohol and dimethyl ether can be carboxylated with the superacidic HF-BF3 system to form methyl acetate and acetic acid. In the carboxylation of methyl alcohol the quantity of acetic acid increased at the expense of methyl acetate with increase in reaction time and temperature. The quantity of the byproduct dimethyl ether, in turn, decreased. Dimethyl ether gave the desired products in about 90% yield at 250°C (90% conversion, catalyst/substrate ratio =1 1, 6h). On the basis of experimental observations, first methyl alcohol is dehydrated to dimethyl ether. Protonated dimethyl ether then reacts with CO to yield methyl acetate [Eq. (5.154)]. The most probable pathway suggested to explain the formation of acetic acid involves the intermediate formation of acetic anhydride through acid-catalyzed ester cleavage without the intervention of CO followed by cleavage with HF [Eq. (5.155)]. 

The spectral nature for the transients formed in the OH reaction with -hydroxybenzaldehyde (Fig. 8) was found to be different from those recorded with its ortho- and meta-isomcrs. In addition to a single peak around 370-410 nm observed with the latter, a more intense peak at 325 nm by four folds was seen. Furthermore, this peak decayed faster with a first-order rate constant k = 5.5 x 10 s"h This decay was found to be acid-catalyzed. In the reaction of OH radical with hydroxybenzaldehydes, the time resolved spectral changes are interpreted in terms of the formation of phenoxyl radical via intermediate radical cation in the case of ortho- and /rm-isomers whereas phenoxyl radical formation by dehydration seems to be the predominant reaction pathway for the w/Jt/r-isomer. 

This chapter focuses on the catalytic transformations that result in the cyclic biosynthesis and breakdown of fatty acids. These metabolic pathways will serve as a paradigm for three classes of chemical reactions carbon-carbon bond formation and cleavage, oxidation and reduction, and hydration—dehydration. The most extensively studied reactions are those involved in microbial fatty acid biosynthesis (Type II fatty acid synthase (FAS-II)) and mammalian fatty acid /3-oxidation. In both pathways, the reactions are catalyzed by separate enzymes that have been cloned and overexpressed, thus providing a ready source of material for structural and mechanistic studies. In contrast, mammalian fatty acid biosynthesis and microbial fatty acid breakdown are catalyzed by multifunctional enzymes (MFEs) that have historically been less amenable to analysis. 

While trying to use allylic alcohols as nucleophiles in Au-catalyzed reactions, electrophilic reactivity was unexpectedly observed and the potential for a variety of mechanistic pathways responsible for this reactivity was intriguing. Au-complexes are typically reported as soft, carbophiUc 7t-acids, but for the observed reaction, it seemed more reasonable that a cationic mechanism whereby the Au-complex functioned as a more traditional oxophilic Lewis acid ° was operative. This piqued our interest, and we decided to change the goals of the project to see where it would take us. Fortunately, pursuing these Au-catalyzed dehydrative transformations developed from a single observation into a research program (vide infra). 

The Knoevenagel reaction is usually catalyzed by bases in concerted acid-base condensation-dehydration pathways similar to the ones depicted in Scheme 4 and 5 for carbonyl compounds. However, the exact nature of the catalyst required for the Knoevenagel condensation depends on the ability of the electron-withdrawing substituent to activate the C—H bond. 

As illustrated in Equations 10.6-10.8, each of the steps along the reaction pathway is reversible, so an alkene may undergo acid-catalyzed hydration to form an alcohol. In practice, reversal of the dehydration may be avoided by removing the alkene, whose boiling point is always lower than the parent alcohol, from the reaction... 

Purpose, This experiment illustrates the variety of pathways that are available to acid-catalyzed elimination reactions of secondary (2°) alcohols via car-bocation intermediates. The dehydration of 2-butanol forms a mixture of gaseous alkene products. The alkenes formed in this reaction are separated and identified by using one of the most powerful instrumental techniques available to the modem research chemist for the separation of complex mixtures gas chromatography (GC). 

The fact that primary carbenium ions are unstable suggests that the exchange with solvent is an Sn2 process with primary alcohols. If true, then are primary carbenium ions ever intermediates in dehydration reactions Studies have shown that it depends upon the case. Neopentyl alcohol does form a primary carbenium ion, whereas 1-propanol does not. Acid-catalyzed elimination of 1-propanol to form propene occurs by a concerted E2 reaction (Eq. 10.90). Similarly, whether a secondary alcohol eliminates in acid via an El or E2 pathway depends on the case. 

A second important reaction of alcohols, both in the laboratory and in biological pathways, is their dehydration to give alkenes. One method that works particularly well for tertiary alcohols is the acid-catalyzed reaction, which... 

Fig. 21. The pathways for acid-catalyzed hydrolysis and dehydration of inulin to 5-HMF.

Antilla and coworkers [64] reported in 2010 the first Bronsted acid-catalyzed true pinacol rearrangement, in which the chiral phosphoric acid diester 34 was the best catalyst for the rearrangement of a series of indolyl diols (Scheme 40.54). A plausible mechanistic pathway for this transformation begins with the acid-induced dehydration of the starting indolyl diol to an intermediate iminium ion, followed by a 1,2-aryl shift (Scheme 40.55). 

---