Ethers, protonated cleavage

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)]. 

Fig. 7-12. Reactions of phenolic /8-aryl ether and a-ether structures (1) during neutral sulfite pulping (Gierer, 1970). R = H, alkyl, or aryl group. The quinone methide intermediate (2) is sulfonated to structure (3). The negative charge of the a-sulfonic acid group facilitates the nucleophilic attack of the sulfite ion, resulting in /8-aryl ether bond cleavage and sulfonation. Structure (4) reacts further with elimination of the sulfonic acid group from a-position to form intermediate (5) which finally after abstraction of proton from /8-position is stabilized to a styrene-/8-sulfonic acid structure (6). Note that only the free phenolic structures are cleaved, whereas the nonphenolic units remain essentially unaffected.

Enantioselective protonation. Cleavage of enol silyl ethers and ketene bis(tri-alkylsilyl) acetals by the complex leads to chiral ketones and esters. 

Reactions of ethers with a mobile proton Cleavage of ketones, rearrangement to alcohols s. 16, 763 ... 

Reactions of ethers with a mobile proton Cleavage to ketones... 

Selective ether cleavage comes about during the substitution step, which obeys an Sn2 mechanism. Therefore, selective cleavage requires selective attack by Y on one of the electrophilic carbons in the protonated ether. Determine if selective attack is likely by examining the shape of the lowest-unoccupied molecular orbital (LUMO) in protonated ethyl propyl ether. Is this orbital larger near one carbon than the other If so, what product combination will result What other atom(s) contribute to the LUMO What would happen if 1 attacked this atom(s) ... 

Repeat this analysis for the reaction of phenyl methyl ether with HI leading to phenol and methyl iodide or methanol and phenyl iodide and involving protonated phenyl methyl ether as an intermediate. (Note In this case, the appropriate empty molecular orbital is LUMO+2 the LUMO is concentrated primarily on the CO bond.) Which reaction, with ethyl propyl ether or phenyl methyl ether, appears to be more likely to give selective ether cleavage ... 

Acidic ether cleavages are typical nucleophilic substitution reactions, either SN1 or Sn2 depending on the structure of the substrate. Ethers with only primary and secondary alkyl groups react by an S 2 mechanism, in which or Br attacks the protonated ether at the less hindered site. This usually results in a selective cleavage into a single alcohol and a single alkyl halide. For example, ethyl isopropyl ether yields exclusively isopropyl alcohol and iodoethane on cleavage by HI because nucleophilic attack by iodide ion occurs at the less hindered primary site rather than at the more hindered secondary site. 

Epoxides are cleaved by treatment with acid just as other ethers are, but under much milder conditions because of ring strain. As we saw in Section 7.8, dilute aqueous acid at room temperature is sufficient to cause the hydrolysis of epoxides to 1,2-diols, also called vicinal glycols. (The word vicinal means "adjacent/ and a glycol is a diol.) The epoxide cleavage takes place by SK2-like backside attack of a nucleophile on the protonated epoxide, giving a trans- 1,2-dio) as product. 

The inertness of phenols and phenoxy phenols toward Na/liq. NH3 can be attributed to the fact that phenols are powerful proton-donors in this system, and resistance of the resultant anions toward reduction is believed to result from stabilization by resonance (10). While alkylation of low-rank coals before treatment with Na/liq. NH3 therefore offers means for establishing the presence of phenoxy phenol ethers in them, an alternative is afforded by the observation that some phenols can be reduced by concentrated solutions of lithium (11). If this latter reaction also reduces phenoxy phenols in coal, a second treatment should then cause ether-cleavage. 

The hydrolysis of diphenhydramine and analogues (11.24, Fig. 11.2) has been studied extensively [46 - 48], These compounds are essentially inert toward base-catalyzed hydrolysis, but do undergo proton-catalyzed hydrolysis, the mechanism of which is shown in Fig. 11.2. The reaction begins with protonation of the ether O-atom and continues with the irreversible heterolytic cleavage of the C-0 bond to produce the benzhydryl cation. This reaction is greatly facilitated by the weakening effect of the benzhydryl moiety on the adjacent C-0 bond. The benzhydryl cation itself is stabilized by resonance, which also explains why the reaction is facilitated. The last step is the for-... 

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