Etherification, acid catalyzed

Substitution Reactions on Side Chains. Because the benzyl carbon is the most reactive site on the propanoid side chain, many substitution reactions occur at this position. Typically, substitution reactions occur by attack of a nucleophilic reagent on a benzyl carbon present in the form of a carbonium ion or a methine group in a quinonemethide stmeture. In a reversal of the ether cleavage reactions described, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers by acid-catalyzed etherifications or transetherifications with alcohol or phenol. The conversion of a benzyl alcohol or ether to a sulfonic acid group is among the most important side chain modification reactions because it is essential to the solubilization of lignin in the sulfite pulping process (17). 

Symmetrical labile ethers such as cycloalkenyl ethers (15) or mixed acetals (16) can also be prepared from the 3-hydroxyl group by acid-catalyzed exchange etherification or by acid-catalyzed addition to cyclohexanone methyl enol ether. 

However, 17a,21-acetonides (103), as well as acetals of other ketones or aldehydes, can be easily prepared by acid-catalyzed exchange reaction with dimethoxypropane or other alkyl acetals in dimethylformamide or benzene. Enol etherification of the A -S-ketone also occurs with the former procedure. 

Formation of the methyl-rhodium complex is analogous to the formation of CH3-C(C0)4 from CH30H2 arid Co(C0K as proposed by Wender. The difference here is that the nature of the active rhodium species is not known. Under the present conditions,homologation does not occur because CO is not present however, addition of the methyl-rhodium species to benzaldehyde must occur as shown in (19), metal adds to the oxygen. The product in (19) is then subject to acid catalyzed etherification to obtain the methyl ether. 

Blocking the C-l OH of D-fructose and L-sorbose (Scheme 25) was effected in excellent yields through regioselective isopropylidene acetalation of the free ketoses, followed by etherification (benzylation or allylation) of the remaining primary alcohol. Acid-catalyzed hydrolysis of the isopropylidene groups and condensation with HSCN efficiently produced a sole fused bicyclic OZT. 

Etherification of glycerol with isobutene (2-methylpropene) is an acid-catalyzed reaction and produces five ethers two monoethers, two diethers and one triether (Fig. 10.2). The IUPAC names for the two monosubstituted ethers are 3-tertiary-butoxypropane-l,2-diol and 2-tertiary-butoxypropanc-1,3-diol, the two disubsti-... 

Acid-catalyzed glycerol etherification probably occurs via an SN1 mechanism, consisting of the consecutive formation of an oxonium and carbenium ion, and its electrophilic attack on a glycerol O atom (Scheme 11.3). 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

In a reversal of the ether cleavage reactions described above, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers via acid-catalyzed etherification or transetherification, respectively, by reaction with the appropriate alcohol or phenol (reaction R, Fig. 1.5). 

The synthesis of orthoesters from nitriles 12 is another example of acid-catalyzed etherification. In this reaction, a nitrile is treated with dry hydrogen chloride and an alcohol to form an iminoester hydrochloride. The dry iminoester hydrochloride is then allowed to react with an alcohol and an orthoester is produced. A possible mechanism for the reaction is the following ... 

Although the carbonium ion representation of aqueous acid-catalyzed etherification and cleavage is quite useful for correlating much important information, the actual course of the reaction must be more complex than it has been indicated here. The very fact that there is so great a difference in the rate at which ethers are hydrolyzed by the halogen acids (IICl HBr HI = 1 6 < ) is a clear indication that the function of the acid is not simply to provide protons for the reaction. 

The reaction undoubtedly proceeds through formation of the hemi-acetal, followed by acid-catalyzed etherification of the hemiacetal by excess alcohol. A possible mechanism is illustrated here. 

This linker was employed in the synthesis of a library of N-alkylated 5- and 6-alkyloxy-l,2,3,4-tetrahydroisoquinolines 77 involving the following steps Michael addition, acid-catalyzed removal of a THP group, Mitsunobu etherification, quaternization of the nitrogen, and Huenig s base-catalyzed elimination [86] (Scheme 36). 

Behr, A. L. Obendorf, L. Development of a process for the acid-catalyzed etherification of glycerine and isobutene forming tertiary butyl ethers. Eng. Life Sei. 2003, 2, 185-189. 

The Lewis acid-catalyzed reaction of carbonyls with MesSi ethers (or alcohols) and hydrosilanes is useful for the synthesis of unsymmetrical ethers [93b]. MesSil and (la) effectively catalyze the reductive etherification via an oxocarbenium ion intermediate. Although MesSiCl is less Lewis acidic, an excess amount of MesSiCl promotes reductive benzylation of alcohols with benzaldehydes and EtsSiH [95]. The (la)-catalyzed reaction of hydroxyketones with EtsSiH has been used for stereoselective construction of cyclic ethers in total synthesis of natural products... 

Another kinetic approach which has been employed for a large number of amides and oxygen bases involves comparison of the strengths of bases through their ability to retard an acid-catalyzed reaction. This has been applied to the p-toluenesulfonic acid catalyzed self-etherification of benzhydrol and the dehydration of terin butyl alcohol in benzene solution (280,281). 

Other experimental methods that have been applied to amide basicities are potentiometric titration (65,164,165) kinetic analysis of acid hydrolj is (100), rate retardation of acid catalyzed etherification of benzhydrol (280), and the Hammett indicator method using NMR (338) or Raman spectrometry (80) for measuring concentrations. 

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