Synthesis of Alcohols ROH

Alcohols are extremely versatile starting materials for organic synthesis, since they can be converted to a wide variety of functional groups. Many simple alcohols are commercially available, but this section will focus on the preparation of alcohols. These synthetic strategies will be useful not only for complex alcohol target molecules (TMs), but also for alcohols that may be intermediates within a larger synthesis. 

Introduction to Strategies for Organic Synthesis, First Edition. Laurie S. Starkey. 2012 John Wiley Sons, Inc. Published 2012 by John Wiley Sons, Inc. 

Alcohols can be prepared from a variety of other functional groups, including by reduction of a carbonyl, hydration of an alkene, or substitution of a leaving group. Remember, regiochemistry is a concern when starting with an alkene, and water can be added with either Markovnikov (oxymercuration-demercuration) or anti-Markovnikov (hydroboration-oxidation) orientation. 

recaU that Sn2 substitution with strongly basic hydroxide (HO ) is reasonable only if there is an unhindered, 1° leaving group, or possibly on a 2° carbon that is allylic (i.e., next to a pi bond) or benzylic (i.e., next to a benzene ring). Otherwise, E2 elimination is the more favorable mechanism. 

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Metal alkoxides and aryloxides, of the general formnla M(OR)x, can be considered as derived from the alcohol ROH by replacement of the hydroxylic hydrogen atom by the metal. These complexes have been known for many years Ti(OEt4) was prepared in 1924 by Bischoff and Adkins/ and the synthesis was attempted as early as 1875 by Demargay although pure product was apparently not obtained. Potential technological applications have resulted in increased activity in this area in recent years (see Sol-Gel Synthesis of Solids)... 

Ethers (ROR ) may be considered to be the anhydrides of alcohols which are formed by the elimination of water from two alcohols (ROH and R OH). Epoxides (oxiranes) are a sub-set of ethers and share many of their characteristics which are derived from the presence of the oxygen lone pairs. However, their much greater reactivity arising from the strained nature of the three membered ring and their wider use in synthesis means that they are best considered separately. 

The major demonstration that alcohols have the formula ROH and ethers R2O, rather than R2O.H2O and R2O respectively was provided by Williamscm himself in his synthesis of mixed ethers ROR (Phil, Mag, [3], 37, 35(W (1850)). On the earlier theory, the reagents potassium ethoxide ami methyl iodide were written C H O-K O and and could only femn two separate ethers,... 

Strictly related to catalytic reactions involving CO and H20 are reactions in which CO and alcohols, ROH, or CO and amines, R2NH, are used as building blocks. The catalytic addition of carbon monoxide and an alcohol to an olefin yields carboxylic esters (hydroesterification). Thus, the synthesis of methyl propionate from ethylene, CO, and methanol using a catalytic system composed of Ru3(CO)u and [PPh4]I (190°C, 20 bar C2H4, 45 bar CO, 2.5 hr, yield 74%, CT 1000) has been reported (323) ... 

Redox-catalyzed migratory insertion of CO into [FeMe(COXPPh3)Cp] rapidly gives a high yield of [Fe(COMeXCOXPPh3)Cp] (531). Synthesis of formic acid esters via oxidation of [FeH(CO)2Cpj by cerium(IV) or copper(II) in alcohols, ROH, also proceeds via initial one-electron oxidation the paramagnetic formyl [Fe(CHOXCO)(ROH)Cp]+ is implicated as an intermediate (532)2 (Section VII,E). 

On heating (150 °C, 10 h) [Fe(CNMe)6]Cl2 is converted to a mixture of cis- and trans-[FeCl2(CNMe)4]. Somewhat surprisingly, [H4Fe(CN)j] reacts with aliphatic alcohols to form [Fe(CN)2(CNR)4] and other complexes. Intermediate species formed during this reaction can polymerize with the evolution of hydrogen cyanide. Addition of HCN displaces isocyanide, however, and so constitutes a catalytic cycle for the synthesis of RNC from HCN and ROH. 

Silica is an attractive material for inorganic gel applications because it is non-toxic, non-flammable and easy to dispose of. Dry silica gels have a translucent, bluish appearance. For gel synthesis at lab-scale, a tetraalkoxysilane Si(OR)4, commonly tetramethoxysilane (TMOS) or tetraethoxysilane (TEOS), dissolved in the respective alcohol ROH, acts as the silica source. When water is added, two chemical reactions occur the first, hydrolysis. 

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