Acid-Catalyzed Elimination of Water

However, when acid-catalyzed elimination of water occurs, and in contrast to reactions of alkyl halides, it is far more common to find (a) Saytzeff (Chapter 7, 

4 TRANSITION STATE FOR ELIMINATION l AV TRANSITION STATE FOR SUBSTITUTION 

Section G, 2), that is, more highly substituted, rather than Hofmann (Chapter 7, Section G, 2), that is, less highly substituted, alkene products and (b) that carbocation rearrangements have occurred. 

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Instead of reducing the ketone function, a lithium organic reagent, e.g. phenyllithium, can be added followed by an acid-catalyzed elimination of water to give product 3.85 This procedure allows the introduction of various substituents. By this method 3-[2-(dimethylamino)ethoxy]-... 

Thus, in contrast to benzothiepins, dibenzo compounds can be synthesized by direct acid-catalyzed elimination of water from hydroxy derivatives, or of amines from amino derivatives, at elevated temperatures due to their thermal stability. As in the case of benzothiepins, dibenzo derivatives can also be prepared by base-catalyzed elimination from the corresponding halo derivatives however, the yields are somewhat lower compared to the acid-catalyzed reactions. As a special case, an aziridine derivative was deaminated by palladium-catalyzed hydrogenation to afford the corresponding dibenzothiepin.69... 

Clearly, the list can be enlarged by introducing additional steps, whereas the steps leading to the reactive species at the beginning (such as the acid-catalyzed elimination of water from an alcohol to form a carbocation) are not counted. 

In the currently accepted mechanistic pathway outlined in Scheme 7, the key step in the Biginelli sequence involves the acid-catalyzed formation of an Wacyliminium ion intermediate of type 719 from the aldehyde and urea precursors <1997JOC7201, 2000ACR879, 20040R1>. Interception of the iminium ion 719 by the CH-acidic carbonyl component 715, presumably through its enol tautomer, produces an open-chain ureide 720, which subsequently cyclizes to hexahydropyrimidine 721. Acid-catalyzed elimination of water from 721 ultimately leads to the... 

The process begins with complete ring closure to compound 13b, since acid-catalyzed elimination of water to the dihydropyridone shills the equilibrium between compounds 13a and 13b. 

In the conversion that gave its name to this reaction, the acid-catalyzed elimination of water from pinacol give s r-butyl methyl ketone. 

Addition of CHsMgBr to cyclohexanone followed by protonation forms an alcohol in Step [3]. Acid-catalyzed elimination of water in Step [4] forms a mixture of alkenes, with the desired trisubstituted alkene as the major product. 

Example 3.9. In an acid-catalyzed elimination of water from an alcohol, water is the leaving group. 

The more nucleophilic nitrogen of the hydrazine reacts at the electrophilic carbon of the carbonyl group. Loss of a proton, facilitated by base ( OAc) is followed by acid-catalyzed elimination of water. 

Kato and his coworkers constructed the aryl-Cs unit by DEPC [(Et0)2P(0)CN)] mediated C-acylation of /-butyl cyanoacetate with phenylpropanoic acid leading, as the key intermediate, to the acetalized beta-ketoaldehyde 148 (114). Addition of 2-phenylethyI magnesium bromide followed by deprotection of die carbonyl group completed the synthesis of the racemic P-ketol 6. Acid catalyzed elimination of water from 6 finally provided the enone 28. 

Hydrogenation of 25 was accomplished using Pearlman s catalyst to provide amino-ester 28 as a 10 1 mixture of diastereoisomers favoring the desired cis isomer.Excess acid (>1 equiv of p-toluensulfonic or sulfuric acid) was necessary to facilitate the hydrogenation by promoting relatively rapid nitrile reduction to protonated amine 26. This protocol prevents catalyst deactivation. Acid also catalyzes the subsequent benzylic alcohol dehydration and the final reduction to 28. The observed increase in diastereoselectivity during the hydrogenation is consistent with acid-catalyzed elimination of water to form intermediate indene 27 followed by reduction from the least hindered face of 27 to afford the cis isomer of 28 as the major product. We did not observe elimination of water prior to nitrile reduction. ... 

Acid-catalyzed elimination of water from 6-hydroxy-2-phenyl-5,6-dihydrothiazolo[2,3-Z>][l,2,4]triazole (144) forms 2-phenylthiazolo[3,2-Z>][l,2,4]triazole (52) <87AP(330)528>. 

The proposed pathway for the conversion is outlined in Eq. 2. The acid-catalyzed elimination of water from the alcohols 1 affording the carbenium ion is followed by a migration of one trimethylsilyl group from the central silicon atom to the neighboring carbon atom and attack of X", the conjugate base of the acid used as the catalyst, at the electrophilic silicon. The hydrolysis of the intermediates 4 gives the silanols 3 [2]. 

The mechanism for acetal formation involves acid-catalyzed formation of the hemiacetal, then an acid-catalyzed elimination of water, followed by a second addition of the alcohol and loss of a proton. 

Ethyl esters are formed by acid-catalyzed elimination of water from a carboxylic acid with ethanol... 

Scheme 8.65. A representation of the acid-catalyzed elimination of water from cis- or (Z)-2-phenylcyclohexanol showing that there is a minimum amount of rearrangement and suggesting that the elimination is largely anticoplanar.

The same research group applied the above methodology for the synthesis of valuable 4//-chromenes 43 in good yields and with excellent enantioselectivities. The approach consists of a dual light and Br0nsted acid mediated isomerization-cyclization reaction starting from enones 41 to yield 27f-chromen-2-ol intermediates A. The subsequent Brpnsted acid catalyzed elimination of water leads to an... 

The silylenol ether formed from (47) and trimethylchlorosilane was cyclized in situ, and the reaction mixture was worked up under acidic conditions to give the ketone (558). This was subjected to reduction with sodium borohydride, acid-catalyzed elimination of water, and oxidation with dichlorodicyanobenzoquinone (DDQ) to give the bicyclic ester (560). Introduction of a methoxy substituent into the retinoid structure (560) was likewise effected via the ketone (558). When this ketone was ketalized with methyl o-formate, methanol was eliminated and the product was oxidized, its six-membered ring system undergoing aromatization to form a substituted phenyl group. 

Sorbitol, a hygroscopic alcohol, is approximately half as sweet as sucrose. It is used as a sweetener for diabetics and in food canning. Sorbitol can be produced on a commercial scale by catalytic hydrogenation of glucose. Acid-catalyzed elimination of water yields a mixture of 1,4-sorbitan (85%, I) and 3,6-sorbitan (15%, II). Under more drastic conditions (action of concentrated acids), I,4 3,6-dianhydrosorbitol (isosorbid III) is formed (Formula 19.2). 

Addition of MeLi to ketocalix[n]arenes (n = 4,5,6 protected as methyl ethers) proceeds in non-stereoselective fashion affording mixtures of stereoisomeric products. Multifold acid-catalyzed elimination of water affords the calixradialenes 24, i.e., calixarenes possessing exocyclic double bonds at the bridges (Eq. 4.17)... 

In synthesis, the most common use of this process is the acid-catalyzed elimination of water from an alcohol to give an alkene. We have already seen a number of syntheses of alcohols we will meet many more in later chapters. Some examples are shown in Figure 10.28 notice that in most cases, there was only one plausible elimination, and an acid with a nonnucleophilic counterion was used. Try writing the mechanisms for each of these reactions—this is always a good practice. 

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