Dehydration reactions alkene synthesis

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. 

Nucleophilic additions to carbonyl groups lead to alcohols which on dehydration, furnish alkenes . This two-step protocol has been extremely useful for diene and polyene synthesis with wide variation in the carbonyl substrate and the nucleophilic addendum. Diene synthesis using aldol-type condensation as well as phenyl sulphonyl carbanion (the Julia reaction) are also discussed in this section. 

During the first total synthesis of taxol , R. Holton and co-workers installed an exo-methylene group on the C ring in order to set the stage for the D ring (oxetane) formation. The Burgess dehydration reaction was applied to a complex tricyclic tertiary alcohol intermediate (ABC rings) and the desired exocyclic alkene was isolated in 63% yield. 

Elimination teactions are the most important means for synthesizing alkenes. In this chapter we shall study two methods for alkene synthesis based on elimination reactions dehydrohalogenation of alkyl halides and dehydration of alcohols. 

Dehydration reactions are important for the synthesis of commodity ethers, such as tetrahydrofuran, which was synthesized from 1,4-butanediol at low yield in NCW. It is also important to note that the reverse reaction can be performed in NCW, although at a greatly reduced yield. For example, the conversion of alkenes to alcohols in NCW has been reported to proceed to < 10% equilibrium conversion. ... 

The biosynthesis of fatty acids is accomplished two carbons at a time by an enzyme complex called fatty acid synthetase. The biochemical reactions involved in fatty acid synthesis are described in Special Topic E WileyPLUS). Each of these biochemical reactions has a counterpart in synthetic reactions you have studied. Consider the biochemical reactions involved in adding each —CH2CH2— segment during fatty acid biosynthesis (those in Special Topic E that begin with acetyl-S-ACP and malonyl-S-ACP, and end with butyryl-S-ACP). Write laboratory synthetic reactions using reagents and conditions you have studied (not biosynthetic reactions) that would accomplish the same sequence of transformations (i.e., the condensation-decarboxylation, ketone reduction, dehydration, and alkene reduction steps). 

Alcohols undergo many reactions and can be converted into many other functional groups. They can be dehydrated to give alkenes by treatment with POCI3 and can be transformed into alkyl halides by treatment with PBr3 or SOCU- Furthermore, alcohols are weakly acidic (p/C, — 16-18) and react with strong bases and with alkali metals to form alkoxide anions, which are used frequently in organic synthesis. 

Problems of acyl anion equivalents met above in the synthesis of similar TMs disappear if (25) is made from the alkene (26), A Wittig is the obvious method to make (26) and reaction between (27) and PhgCO will probably give (26), An alternative is the dehydration of (28), made by Grignard addition to ester (20), Osmium tetroxide was used for the hydroxylation. 

The earliest reported Fxs were the result of the reaction of nitrous acid with naturally occurring alkenes being the identified intermediate a a-nitrooxime that suffers dehydration with cyclization. Apart from these conditions, the most recent Fxs synthesis descriptions have involved reactions between alkenes and dinitrogen trioxide (Fig. 3), nitroalkanes and aluminum trichlo-... 

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). 

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. 

In the synthesis we should not wish to make 21 as it would cyclise and, in any case, we d rather reduce nitrile, nitro and alkene all in the same step by catalytic hydrogenation. The very simple method used for the conjugate addition is possible only because of the slow aldol reaction of the hindered aldehyde 24. The aldol 25, also called a Henry reaction, needs a separate dehydration step but the three functional groups in 26 are reduced in one step in good yield.7... 

This bimolecular dehydration of alcohols is a type of condensation, a reaction that joins two (or more) molecules, often with the loss of a small molecule such as water. This method is used for the industrial synthesis of diethyl ether (CH3CH2—O—CH2CH3) and dimethyl ether (CH3—O—CH3). Under the acidic dehydration conditions, two reactions compete Elimination (dehydration to give an alkene) competes with substitution (condensation to give an ether). 

CHAPTER 7 CHAPTER 8 CHAPTER 10 CHAPTER 11 CHAPTER 15 CHAPTER 17 CHAPTER 18 Acid-Catalyzed Dehydration of an Alcohol 313 Electrophilic Addition to Alkenes 330 Grignard Reactions 443 The Williamson Ether Synthesis 500 The Diels-Alder Reaction 684 Electrophilic Aromatic Substitution 757 Nucleophilic Additions to Carbonyl Groups 841 Formation of Imines 851 Formation of Acetals 856... 

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... 

The synthesis of stereodefined acyclic alkenes via 3-elimination reactions—such as (1) dehydration of alcohols, (2) base-induced eliminations of alkyl halides or sulfonates (tosyl or mesyl esters), and (3) Hofmann eliminations of quaternary ammonium salts—often suffers from a lack of regio- and stereoselectivity, producing mixtures of isomeric alkenes. 

In the laboratory of T.-L. Ho, the total synthesis of the novel marine sesquiterpene (+)-isocyanoallopupukeanane was completed." In the endgame of the synthesis, it was necessary to install the isocyano group onto the tricyclic trisubstituted alkene substrate so that it will occupy the more substituted carbon atom (according to Markovnikov s rule). The Ritter reaction was chosen to form the required carbon-nitrogen bond. The alkene substrate was dissolved in glacial acetic acid and first excess sodium cyanide followed by concentrated sulfuric acid was added at 0 °C. The reaction mixture was stirred at ambient temperature for one day and then was subjected to aqueous work-up. The product A/-alkyl formamide was subsequently dehydrated with tosyl chloride in pyridine to give rise to the desired tertiary isocyanide which indeed was identical with the natural product. 

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