Add-catalyzed dehydration

Problem 18.2 Why do you suppose only symmetrical ethers are prepared by the sulfuric add-catalyzed dehydration procedure What product(s) would you expect if ethanol and 1-propanol were allowed to react together In what ratio would the products be formed if the two alcohols were of equal reactivity ... 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the thiol group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and add-catalyzed dehydration would then lead to the thiazolidine and lactam rings. The stereochemistry at the carboxylic add a-... 

Add-catalyzed dehydration, lignin model compounds, 130-131 Activating fragments, definition, 54... 

FIGURE 5.6 The mechanism for the add-catalyzed dehydration of tert-butyl alcohol. 

This reaction illustrates identical reactivity at two equivalent sites in a molecule. Both alcohol functions are tertiary and benzylic and undergo add-catalyzed dehydration readily. 

The second half begins like an add-catalyzed dehydration, but then another alcohol adds. 

An example of a reaction leading to gaseous products that can use this collection technique is the add-catalyzed dehydration of 2-butanol described in Experiment [9], The products of this reaction are a mixture of aUcenes 1-butene, trans-2-hutene, and cis-2-butene, which boil at —6.3,0.9, and 3.7°C respectively and s c-butyl ether (2,2 -oxybisbutane) which boils at 123 °C. While all four compounds are formed in the reaction mixture, the setup is designed to collect the gases and thus the three alkenes. 

An alcohol can be converted to an alkene by dehydration (i.e by the elimination of a molecule of water from adjacent carbon atoms). Dehydration is most often brought about by heating the alcohol with either 85% phosphoric acid or concentrated sulfuric acid. Primary alcohols are the most difficult to dehydrate and generally require heating in concentrated sulfuric acid at temperatures as high as 180°C. Secondary alcohols undergo acid-catalyzed dehydration at somewhat lower temperatures. Add-catalyzed dehydration of tertiary alcohols often requires temperatures only slightly above room temperature. 

Thus, the ease of add-catalyzed dehydration of alcohols is in this order 1° alcohol < 2° alcohol < 3° alcohol... 

As an illustration of the principle of microscopic reversibility, notice that the mechanism presented in this section for the add-catalyzed dehydration of 2-butanol to give 2-butene is exactly the reverse of that presented in Section 6.3B for the acid-catalyzed hydration of 2-bufene fo g ive 2-butanol. 

Cyclohexanol can undergo add-catalyzed dehydration to form cyclohexene. 

The initial reaction is probably the add-catalyzed hydration of the triple bond, followed by dehydration of the 17-hydroxyl group 105... 

Furan-2,5-dicarboxylic add also has tremendous industrial potential, because it could replace oil-derived diadds such as adipic or terephthalic acid as monomers for polyesters and polyamides [98, 99]. This diadd can be synthesized by Pt-catalyzed oxidation with 02 of 5-hydroxymethylfurfural the latter is obtained by acid-catalyzed dehydration of D-frudose or frudosans (inulin) the latter, however, are too expensive as starting materials, and yields from glucose-based waste raw materials are no higher than 40%. Therefore, the potential attractive option of furan-2,5-dicarboxylic acid will develop only after an effident generation of 5-hydroxymethylfurfural from forestry waste materials has been developed. The same compound is also the starting material for the synthesis of other interesting chemicals obtained by oxidative processes, such as 5-hydroxymethylfuroic add, 5-formylfuran-2-carboxylic add and the 1,6-dialdehyde. 

Treatment of an alkene with a strong acid, such as sulfuric acid, that has a relatively nonnucleophilic conjugate base results in the addition of the elements of water (H and OH) to the double bond. This reaction has many similarities to the addition of the halogen acids described in Section 11.2. First H+ adds to produce a carbocation and then water acts as the nucleophile. The reaction follows Markovnikov s rule and the stereochemistry is that expected for a reaction that involves a carbocation—loss of stereochemistry. Some examples are provided in the following equations. Note that the mechanism is the exact reverse of the El mechanism for acid-catalyzed dehydration of alcohols described in Section 10.13. 

Scheme 3. Preparation of tetraphenyl-Cp by condensation of phenylacetophenone (des-oxybenzoin) and formaldehyde in a base-catalyzed reaction followed by reductive cyclization of the 1,5-diketone with zinc in acetic add and dehydration of the 1,2-diols (32,33,43). The yield is 60%. The bromide synthesis is based on Ref. (44) (yield 70%).

In Section 4.5, we saw that an alkene is hydrated (adds water) in the presence of an acid catalyst, thereby forming an alcohol. The hydration of an alkene is the reverse of the acid-catalyzed dehydration of an alcohol. 

In a number of other studies, GC-MS of DMOX derivatives has been utilized to determine the CLA isomer distribution from a variety of sources. The structures of pure isomers of 9c,llt-18 2 and 10f,12c-18 2, isolated by crystallization of a CLA mixture prepared by alkali-isomerization of linoleate, were confirmed (67). The presence of 9c,llt-18 2 was established in chocolate (49). In conjunction with GC-FTIR, all possible geometrical isomers of 9,11-18 2 (c,i > t,t > c,c and t,c) were detected in human adipose tissue (10). In dehydrated castor oil, although the 9,11 isomers (c/i, c,c and t,t) appeared to be the most abundant, 7,9- and 8,10-18 2 (c/t and but not c,c) were also detected with the aid of SPA (46). The presence of It, 9c-18 2 (as well as lower levels of 7c,9c-, lt,9t- and possibly 7c,9f-18 2) was confirmed in cow s milk, cheese, beef, and human milk and adipose tissue (9). Together with silver-ion HPLC, the isomer distribution in different tissues of pigs fed commercial CLA was determined (2). The CLA content of lactic acid bacteria (44), and the nature of the CLA isomers formed as a result of add-catalyzed methylation of allylic hydroxy oleates (secondary hpid autoxidation products) (47) were also established. 

In the oxazole system, the structural element of a bridged 2-aza-l,3-diene is present. Therefore, oxazoles are enabled to undergo Diels-Alder reactions with activated alkenes and alkynes. For example, acryhc acid (as an unsymmetrical activated dienophile) adds to the oxazole 13 to give the product 14 of a (4 + 2)-cycloaddition regioselectively. The Diels-Alder adduct 14 can be transformed to the pyridine derivative 15 by acid-catalyzed dehydration. 

In a synthesis of flavanones [330], saUcylaldoxime (21) is converted to the hydrox-amic add chloride 22 by reaction with NCS. The nitrile oxide, formed from 22 on treatment with KHCO3, undergoes regioselective cycloaddition to styrene to afford the 3,5-diaryhsoxazohne 23. Catalytic hydrogenation of 23 leads to the fS-hydroxyketone 25, which after acid-catalyzed dehydration cydizes to the flavanone 24. 

Polymerization initiated by phosphoric or metaphosphoric add, or their alkylammonium salts, in the absence of water, proceeds probably through a hydrolytic mechanism. Indeed, phosphoric acid at the polymerization temperatures rmdetgoes dehydration and the lactam amide group is then hydrolyzed. The resultant diphosphoric add catalyzes both hydrolysis and propagation. 

In Summary Carboxylic acids react with alcohols to form esters, as long as a mineral acid catalyst is present. This reaction is only shghtly exothermic, and its equilibrium may be shifted in either direction by the choice of reaction conditions. The reverse of ester formation is ester hydrolysis. The mechanism of esterification is add-catalyzed addition of alcohol to the carbonyl group followed by acid-catalyzed dehydration. Intramolecular ester formation results in lactones, favored only when five- or six-manbered rings are produced. 

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