Alcohols acid-catalyzed

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. 

For synthesis of an alcohol, acid-catalyzed hydration of an alkene is useful in all of the following instances except ... 

H NMR spectrum, 817 in mixed Claisen condensation, 836 2-Methyl-2-propanol, 138. See also tert-Butyl alcohol acid-catalyzed dehydration, 182 2-Methylpropene. See also Isobutene Isobutylene... 

C. SYNTHESIS OF ALCOHOLS Acid-Catalyzed Reaction Sample reaction 21-1... 

It is possible to shift ester hydrolyses away from the normal Aac2 or Bac2 mechanisms by structural changes in the substrate. When the ester is derived from a tertiary alcohol, acid-catalyzed hydrolysis often shifts to a mechanism involving alkyl-oxygen fission. This shift is due to the stability of the carbonium ion that can be formed by C-O heterolysis, and probably also to a decrease in the rate of nucleophilic attack at the carbonyl group because of steric factors. Alkenes, as well as alcohols, may be produced from the carbonium ion, since water can function either as a nucleophile or as a Br0nsted base. 

Three of the six reactions are well suited for the synthesis of alcohols acid-catalyzed hydration, oxymercuration (after reduction of the C-Hg bond by NaBHi), and hydroboration (by oxidation of the C-B bond by H2O2). Compare the alcohol from hydration (shown earlier) with that from demer-curation of the oxymercuration product ... 

Acid-catalyzed alkylation of aromatics with alcohols themselves is widely used. Whereas tertiary (and secondary) alcohols react with rel-... 

Synthesis of (A) started with the combination of 2,4,6-trimethylphenol and allyl bromide to give the or/Ao-allyl dienone. Acid-catalyzed rearrangement and oxidative bydroboration yielded the dienone with a propanol group in porlactone ring were irons in the product as expected (see p. 275). Treatment with aqueous potassium hydroxide gave the epoxy acid, which formed a crystalline salt with (R)-l-(or-naphthyl)ethylamine. This was recrystallized to constant rotation. 

Zaitsev s rule as applied to the acid catalyzed dehydration of alcohols is now more often expressed in a different way elimination reactions of alcohols yield the most highly substituted alkene as the major product Because as was discussed in Section 5 6 the most highly substituted alkene is also normally the most stable one Zaitsev s rule is sometimes expressed as a preference for predominant formation of the most stable alkene that could arise by elimination... 

These common features suggest that carbocations are key intermediates m alcohol dehydra tions just as they are m the reaction of alcohols with hydrogen halides Figure 5 6 portrays a three step mechanism for the acid catalyzed dehydration of tert butyl alcohol Steps 1 and 2 describe the generation of tert butyl cation by a process similar to that which led to its for matron as an intermediate m the reaction of tert butyl alcohol with hydrogen chloride... 

FIGURE 5 6 The El mecha nism for the acid catalyzed dehydration of tert butyl alcohol... 

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... 

You may have noticed that the acid catalyzed hydration of an alkene and the acid catalyzed dehydration of an alcohol are the reverse of each other... 

IS reversible with respect to reactants and products so each tiny increment of progress along the reaction coordinate is reversible Once we know the mechanism for the for ward phase of a particular reaction we also know what the intermediates and transition states must be for the reverse In particular the three step mechanism for the acid catalyzed hydration of 2 methylpropene m Figure 6 9 is the reverse of that for the acid catalyzed dehydration of tert butyl alcohol m Figure 5 6... 

Acid catalyzed hydration converts alkenes to alcohols with regioselectivity according to Markovnikov s rule Frequently however one needs an alcohol having a structure that corresponds to hydration of an alkene with a regioselectivity opposite to that of Markovnikov s rule The conversion of 1 decene to 1 decanol is an example of such a transformation... 

Oxidation of tridecylborane gives 1 decanol The net result is the conversion of an alkene to an alcohol with a regioselectivity opposite to that of acid catalyzed hydration... 

We now have a new problem Where does the necessary alkene come from Alkenes are prepared from alcohols by acid catalyzed dehydration (Section 5 9) or from alkyl halides by dehydrohalogenation (Section 5 14) Because our designated starting material is tert butyl alcohol we can combine its dehydration with bromohydrm formation to give the correct sequence of steps... 

Although 2 methylpropene undergoes acid catalyzed hydration m dilute sulfuric acid to form tert butyl alcohol (Section 6 10) a different reaction occurs m more concentrated solutions of sulfuric acid Rather than form the expected alkyl hydrogen sulfate (see Sec tion 6 9) 2 methylpropene is converted to a mixture of two isomeric C Hig alkenes... 

As a method for the preparation of alkenes a weakness in the acid catalyzed dehydration of alcohols IS that the initially formed alkene (or mixture of alkenes) sometimes isomenzes under the conditions of its formation Write a stepwise mechanism showing how 2 methyl 1 butene might isomenze to 2 methyl 2 butene in the presence of sulfuric acid... 

We have seen this situation before m the reaction of alcohols with hydrogen halides (8ection 4 11) m the acid catalyzed dehydration of alcohols (8ection 5 12) and m the conversion of alkyl halides to alkenes by the El mechanism (8ection 5 17) As m these other reactions an electronic effect specifically the stabilization of the carbocation intermediate by alkyl substituents is the decisive factor The more stable the carbo cation the faster it is formed... 

Acid catalyzed dehydration of benzyhc alcohols is a useful route to alkenylben zenes as is dehydrohalogenation under E2 conditions... 

Addition of phenylmagnesium bromide to 4 tert butylcyclohexanone gives two isomeric ter tiary alcohols as products Both alcohols yield the same alkene when subjected to acid catalyzed dehydration Suggest reasonable structures for these two alcohols... 

FIGURE 15 3 The mecha nism of acid catalyzed for mation of diethyl ether from ethyl alcohol... 

Acid catalyzed condensation of an alcohol and a carboxylic acid yields an ester and water and IS known as the Fischer esterification... 

Because they are widely used as solvents many simple dialkyl ethers are commercially available Diethyl ether and dibutyl ether for example are prepared by acid catalyzed condensation of the corresponding alcohols as described earlier m Section 15 7... 

Acid catalyzed addition of alcohols to alkenes is sometimes used Indeed before Its use as a gasoline additive was curtailed billions of pounds of tert butyl methyl ether (MTBE) was prepared by the reaction... 

Epoxidation of an alkene followed by lithium aluminum hydride reduction of the result mg epoxide gives the same alcohol that would be obtained by acid catalyzed hydration (Section 610) of the alkene... 

Steps 4-5 Conversion of hemiacetal to carbocation These steps are analogous to the formation of carbocations m acid catalyzed reactions of alcohols... 

Acryhc esters may be saponified, converted to other esters (particularly of higher alcohols by acid catalyzed alcohol interchange), or converted to amides by aminolysis. Transesterification is comphcated by the azeotropic behavior of lower acrylates and alcohols but is useful in preparation of higher alkyl acrylates. 

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