Alkene Synthesis by Dehydration of Alcohols

Dehydration of alcohols is a common method for making alkenes. The word dehydrtition literally means removal of water.  

Dehydration is reversible, and in most cases the equilibrium constant is not large. In fact, the reverse reaction (hydration) is a method for converting alkenes to alcohols (see Section 8-4). Dehydration can be forced to completion by removing the products 

Concentrated sulfuric acid and/or concentrated phosphoric acid are often used as reagents for dehydration because these acids act both as acidic catalysts and as dehydrating agents. Hydration of these acids is highly exothermic. The overall reaction (using sulfuric acid) is 

Hydration and dehydration reactions are common in many biological pathways. The enzyme fumarase catalyzes the reversible addition of water to the double bond of fu-marate to form malate. In contrast to the harsh conditions used in the chemical reaction, the enzymatic reaction takes place at neutral pH and at 37 C. 

Alcohol dehydrations usually involve El elimination of the protonated alcohol. 

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Dehydrogenation of alkanes is not a practical laboratory synthesis for the vast majority of alkenes The principal methods by which alkenes are prepared m the labo ratory are two other (3 eliminations the dehydration of alcohols and the dehydrohalo genation of alkyl halides A discussion of these two methods makes up the remainder of this chapter... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Ethers are prepared from alkyl halides by the treatment of metal alkoxide. This is known as Williamson ether synthesis (see Sections 4.3.6 and 5.5.2). Williamson ether synthesis is an important laboratory method for the preparation of both symmetrical and unsymmetrical ethers. Symmetrical ethers are prepared by dehydration of two molecules of primary alcohols and H2SO4 (see Sections 4.3.7 and 5.5.3). Ethers are also obtained from alkenes either by acid-catalysed addition of alcohols or alkoxymercuration-reduction (see Section 5.3.1). 

The Wittig alkenation has found widespread application in synthetic organic chemistry, and numerous papers and reviews have detailed the progress of the Wittig reaction. A principal advantage of alkene synthesis by the Wittig reaction is that the location of the double bond is absolutely fixed in contrast to the mixture often produced by alcohol dehydration. With simple substituted ylides Z-alkenes are favoured. 

Dehydration of alcohols over solid catalysts can yield alkenes by intramolecular dehydration, whereas ethers are the product of an intermolecular process. The catalysts used can be acidic or basic solids or bifunctional acid-base materials. Although selective synthesis of any desired product is possible, complications can arise as a result of side-reactions-dehydrogenation and decomposition of the starting alcohol, decomposition and consecutive transformations of intermediates and products (j9-cleavage of carbocations, oligomerization of alkenes). 

When monohydric alcohols undergo dehydration, isomeric alkenes can be formed by the loss of water by f (or 1,2-) elimination. Selective synthesis of certain alkenes can, however, be accomplished-when primary alcohols are treated with appropriate solid catalysts terminal alkenes are formed. In contrast, either 1- or 2-alkenes can be produced by dehydration of secondary 2-alkanols. The reactivity of alcohols follows the sequence tertiary > secondary > primary. 

Important information about the stereochemistry of dehydration has been obtained by studying the transformation of cyclic alcohols many of these reactions have proved suitable for the selective synthesis of alkenes [2]. The dehydration of menthol (5) and neomenthol (6) illustrates the usefulness of such processes (Scheme 3 axial hydrogens participating in water loss to form the major menthene isomers are shown) [55]. The regioselectivity observed points to an anti elimination mechanism. Isomer 6, with a trans OH/H configuration in the most stable conformation, reacts faster than compound 5. 

In Summary The carbocation formed by addition of a proton to an alkene may be trapped by water to give an alcohol, the reverse of alkene synthesis by alcohol dehydration. Reversible protonation equilibrates alkenes in the presence of acid, thereby forming a thermodynamically controlled mixture of isomers. 

One of the most general reaction sequences for the transformation of ketones into alkenes is reduction of the ketone to the corresponding alcohol followed by dehydration. While this method has been widely used, it often suffers from a lack of both stereo- and regio-chemical control in the formation of the double bond. Since the reduction of ketones and the subsequent dehydration of the resultant alcohols are covered in depth in other sections (this volume, Chapter 1.1 and Volume 6, Chapter 5.1), we present here only a few representative examples and divert the reader to these other sections for a detailed analysis of this area. In the total synthesis of (+)-occidentalol (Scheme 4), 1,2-reduction of the enone moiety gave... 

No doubt joining the alkyne to the alkene could also have been done by a coupling reaction in the coordination sphere of a metal but an alternative is to imagine the alkene as coming from the dehydration of an alcohol 251. This allows disconnection to the known lactone 250. The synthesis of the alkyne uses DIBAL for partial reduction and the differential protection of the two OH groups by more or less hindered silyl groups. 

This involves a complex mechanistic reaction sequence. First, the alkene is acylated to produce the cationic intermediate 29, followed by deprotonation to the enol 30. Renewed acylation furnishes the cationic 1,5-dicarbonyl system 31 which, by dehydration, is transformed into 28. Formation of the product can be controlled by the use of Lewis acid. The use of alcohols or halogen compounds for the in situ generation of alkenes is a preparatively important variation of the Balaban synthesis [6]. 

While special cases might be imagined where dehydration could favor one alkene rather than another, the situation depicted for cyclohexanone in Scheme 9.74 is typical. Aldehydes generally behave similarly with the potential for dehydration of the alcohol generated by the addition routinely realized. However, utilizing P-acyloxysulfones (the Julia synthesis) regioselective double bond introduction is possible. 

The resurgent interest in the synthetic utility of 1-nitro-alkenes is evidenced by the variety of recent reports concerning their preparation. " Thus, the dehydration of 2-nitro-alcohols with sodium hydride or dicyclohexylcarbo-di-imide, the dehydrohalogenation of a-halogeno-oximes, and the nitro-selenylation of alkenes followed by oxidative deselenylation all provide 1-nitro-alkenes in moderate to excellent yield. In particular, these methods are all applicable to the synthesis of conjugated cyclic nitro-alkenes and complement those procedures previously reported for the preparation of both cyclic and acyclic nitro-alkenes (Vol. 3, p. 175 Vol. 4, p. 183 Vol. 5, p. 196 Vol. 6, p. 208). 

Bimolecular dehydration is generally used for the synthesis of symmetrical ethers from unhindered 1° alcohols. Industrially, diethyl ether is obtained by heating ethanol at 140 °C in the presence of H2SO4. In this reaction, ethanol is protonated in the presence of an acid, which is then attacked hy another molecule of ethanol to give diethyl ether. This is an acid-catalysed Sn2 reaction. If the temperature is too high, alkene is formed via elimination. 

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