Preparations of Alcohols

SECTION 32 ALCOHOLS AND THIOLS FROM ACID DERIVATIVES 

The following reaction types are included in this section  

Coupling of Aldehydes to form Diols is found in Section 323 (Alcohol-Alcohol). 

toluene-hexane, rt 5% 2-azanorbornyl-oxazolidine catalyst 

Lombardo. M. Girotti, R. Morganti, S. Tromhini. C. Chem. Commun., 2001, 2310. 

The mass spectra of alcohols may not always show strong molecular ions. The reason is that the M+ ions readily fragment by a cleavage. The fragment ions are relatively stable and are the gaseous counterparts of protonated aldehydes and ketones  

Many of the common laboratory methods for the preparation of alcohols have been discussed in previous chapters or will be considered later thus to avoid undue repetition we shall not consider them in detail at this time. Included among these methods are hydration (Section 10-3E) and hydroboration (Section 11-6D), addition of hypohalous acids to alkenes (Section 10-4B), SN1 and Sn2 hydrolysis of alkyl halides (Sections 8-4 to 8-7) and of allylic and benzylic halides (Sections 14-3B and 14-3C), addition of Grignard reagents to carbonyl compounds (Section 14-12), and the reduction of carbonyl compounds (Sections 16-4E and 16-5). These methods are summarized in Table 15-2. 

Some of the reactions we have mentioned are used for large-scale industrial production. For example, ethanol is made in quantity by the hydration of ethene, using an excess of steam under pressure at temperatures around 300° in the presence of phosphoric acid  

A dilute solution of ethanol is obtained, which can be concentrated by distillation to a constant-boiling point mixture that contains 95.6% ethanol by weight. Dehydration of the remaining few percent of water to give absolute alcohol is achieved either by chemical means or by distillation with benzene, which results in preferential separation of the water. Ethanol also is made in large quantities by fermentation, but this route is not competitive for industrial uses with the hydration of ethene. Isopropyl alcohol and tert-butyl alcohol also are manufactured by hydration of the corresponding alkenes. 

Reaction of organometallic compounds with carbonyl compounds a. primary alcohols from methanal (formaldehyde) 

The user should bear in mind that the pairs of functional groups alcohol, ester carboxylic acids, ester amine, amide and carboxylic acid, amide can be interconverted by simpie reactions. Compounds of the type RCH(0Ac)CH20Ac (ester-ester) would thus be of interest to anyone preparing the diol RCH(OH)CH20H (alcohol-alcohol). 

SECTION 5 ALKYNES FROM ALKYLS, METHYLENES AND ARYLS 

SECTION 9 ALKYNES FROM ETHERS, EPOXIDES AND THIOETHERS 

For examples of the reaction RC CH - RCsC-CsCRl, see section 300 (Alkyne-Alkyne). 

Iwamura. M. Ishikawa, T. Koyama, Y. Sakuma, K. Iwamura, H. Tetrahedron Lett., 1987, 28, 679. 

With these caveats in mind, let s see how to use these substitution reactions to prepare a variety of functional groups. 

Alcohols are widely available from a number of reactions that are described in subsequent chapters. For this reason they are often the starting materials for the preparation of other functional groups using substitution reactions. However, they can be prepared from alkyl halides, when necessary, by using either water or hydroxide ion as the nucleophile. A general equation for the reaction using hydroxide ion as the nucleophile is 

Hydroxide ion, the conjugate base of water, is a strong base and a strong nucleophile and reacts by the SN2 mechanism. As illustrated in the following example, hydroxide ion gives good yields of alcohols with primary alkyl halides  

Yields are also acceptable for reactions of hydroxide ion with secondary alkyl halides if the compound is especially favorable for SN2 reactions (halides that are allylic, ben-zylic, or adjacent to a carbonyl group), as shown in the following example  

Hydroxide ion is seldom used as a nucleophile with unactivated secondary halides and never with tertiary halides because of competing E2 elimination reactions. For such compounds, replacement of the halide with OH can be accomplished by using water as a nucleophile and SN1 conditions  

For many years, most efforts directed towards the development of solid-phase preparations of alcohols had been limited to the synthesis of biopolymers, such as oligonucleotides and oligosaccharides. Interest in the preparation and chemical transformation of all types of alcohol on insoluble supports only began to grow rapidly in the early 1990s, when chemists realized the potential of parallel solid-phase synthesis for high-throughput compound production. 

10% chiral amino acid ligand hexane. 4°C. 1 d 

chiral Cr/Mn - allyl bromide complex, 2 TMSC1 2. TBAF 

Superchi, S. Giorgio, E. Scafato, P. Rosini. C. Tetrahedron Asymmetry 2002,13, 1385. 

Malhotra. S.V. Tetrahedron Asymmetry 2003,14,1763. phono Et2Zn, toluene, chiral diamine 

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PREPARATION OF ALCOHOLS BY REDUCTION OF CARBOXYLIC ACIDS AND ESTERS... 

Much of the chemistry of diols—compounds that bear two hydroxyl groups—is analo gous to that of alcohols Diols may be prepared for example from compounds that con tain two carbonyl groups using the same reducing agents employed m the preparation of alcohols The following example shows the conversion of a dialdehyde to a diol by... 

Preparation of Alcohols by Reduction of Carbonyl Functional Groups... 

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

Dehydration. Dehydration of amyl alcohols is important for the preparation of specialty olefins and where it may produce unwanted by-products under acidic reaction conditions. Olefin formation is especially facile with secondary or tertiary amyl alcohols under acidic conditions. The reverse reaction, hydration of olefins, is commonly used for the preparation of alcohols. 

Organolithium and organomagnesium compounds find their- chief use in the preparation of alcohols by reaction with aldehydes and ketones. Before discussing these reactions, let us first exanine the reactions of these organometallic compounds with proton donors. 

This compound can disproportionate, generating silane (SiH4) which is liable to be pyrophoric. Presumably other alkoxy silanes can do likewise [ 1 ]. Its use as a reducing agent for the preparation of alcohols from esters is considered safer in air than under... 

The Henry reaction of nitroalkanes followed by denitration is a good method for the preparation of alcohols. This methodology has been applied in carbohydrate chemistry. For... 

Sugars from a wide variety of sources can be used in the preparation of alcoholic beverages. 

Preparation of enantiomerically pare secondary amines by catalytic asymmetric hydrogenation or hydrosilylation of imines is as important as the preparation of alcohols from ketones. However, asymmetric hydrogenation of prochiral ON double bonds has received relatively less attention despite the obvious preparative potential of this process.98... 

Another method, in particular for the preparation of alcohols from ketones involves the transfer of hydrogen from a hydrogen donor. The classic example is the commercially applied Meerwein-Ponndorff-Verley reaction, which uses stoichiometric amounts of Al(O Pr)3 to produce acetone and the alkoxides of the alcohols desired [31], The catalytic version of this reaction, employing... 

Both older methods for the reduction of esters to alcohols, catalytic hydrogenation and reduction with sodium, have given way to reductions with hydrides and complex hydrides which have revolutionized the laboratory preparation of alcohols from esters. 

The method of photosensitized oxygenation was successfully applied in the preparation of alcohols 265-270 from sylvestrene (264),207 and seems to be the most simple and successful method for the preparation of optically active rose oxides (272,273) from (+)- or (—)-citronellol C271).177 It may also be used for the preparation of certain organo-metallic hydroperoxides. Thus, the triphenyl-tin derivative of tri-methylethylene (274) undergoes a photosensitized oxygenation reaction with a rate similar to that of tetramethylethylene, giving rise to the hydroperoxides 275 and 276 219... 

Oxymercuration-reduction of alkenes preparation of alcohols Addition of water to alkenes by oxymercuration-reduction produces alcohols via Markovnikov addition. This addition is similar to the acid-catalysed addition of water. Oxymercuration is regiospecific and auft -stereospecific. In the addition reaction, Hg(OAc) bonds to the less substituted carbon, and the OH to the more substituted carbon of the double bond. For example, propene reacts with mercuric acetate in the presence of an aqueous THF to give a hydroxy-mercurial compound, followed by reduction with sodium borohydride (NaBH4) to yield 2-propanol. 

Addition of sulphuric acid to alkenes preparation of alcohols... 

Preparation of alcohols Ethylene oxide can be easily cleaved by HBr to give bromoethanol. The oxygen is protonated to form a protonated ethylene oxide, which, being attacked by the halide, gives bromoethanol. 

Preparation of alcohols Organometallic reagents (RMgX, RLi) are powerful nucleophiles. They attack epoxides at the least hindered carhon, and generate alcohols. For example, propylene oxide is an unsymmetrical epoxide, which reacts with methyl magnesium bromide to produce 2-butanol, after the acidic work-up. 

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