Some Reactions of Alcohols

Reactions of alcohols can be divided for convenience into two groups—those that occur at the C-0 bond and those that occur at the 0-H bond  

Let s begin looking at reactions of both types by reviewing some of the alcohol reactions seen in previous chapters. 

One of the most valuable C-O bond reactions of alcohols is dehydration to give alkenes. The C-0 bond and a neighboring C-H are broken, and an alkene it bond is formed  

Because of the usefulness of the reaction, a number of ways have bea devised for canying out dehydrations. One method that works particu arl well for tertiary alcohols is the acid-catalyzed reaction discussed in Sectionj 7.1. For example, treatment of 1-methylcyclohexanoI with warm aqueou sulfuric acid in a solvent such as tetrahydrofuran results in loss of wat and formation of 1-methylcyciohexene. 

Acid-catalyzed dehydrations usually follow Zaitsev s rule (Section 11.1 and yield the more highly substituted alkene as the major product. Thus, 2-methyl-2-butanol gives primarily 2-methyl-2-butene (trisubstituted double bond) rather than 2-methyl-l-butene (disubstituted double bond). 

In this reaction the alcohol is oxidised (each molecule loses two atoms of hydrogen), and the product is called an aldehyde. For ethanol, the aldehyde is called ethanal, ethan because it has two carbon atoms and -al because it contains an aldehyde group (CHO) as part of the carbon chain. The names of all aldehydes end in al . It is the ethanal that causes the wine to smell of sour apples when it begins to go sour in the air to form ethanoic acid. 

It is the ethanoic acid that causes the wine to go off and taste sour and smell of vinegar if the bottle is left open to the air. 

primary alcohols oxidise to aldehydes secondary alcohols oxidise to ketones tertiary alcohols are not oxidised. 

Unlike aldehydes, ketones are resistant to further oxidation. They cannot usually be oxidised by the air but can be oxidised with powerful reagents like potassium dichromate(VI) mixed with concentrated sulfuric acid, with the breaking of the carbon-riarbon chain. 

One way to tell the difference between primary, secondary and tertiary alcohols is to test to see which are oxidised, and then test the products for the presence of aldehydes and ketones. Tertiary alcohols will not be oxidised careful oxidation of primary alcohols gives an aldehyde (if oxidised too strongly a carboxylic acid is formed) and secondary alcohols form ketones. 

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Some reactions of alcohols 104 with isocyanates (93T6849) have been reported, as have reactions of acyl halides with 104 (R = SMe), 105 (93T6849), and 106 (93CC417). In turn, alcohols of type 104 and 105 have been prepared by lithium aluminium hydride reduction of the corresponding ketones or through deprotection of their O-rm-butyldiphenylsilyl derivatives (91TL6033 93T6849). 

We recall that in some reactions of alcohols in which either the C—O or the O—H bond breaks, a C—H bond also breaks. If this bond is on the carbon atom adjacent to the carbon atom bearing the hydroxyl group, the reaction is a 3-elimination. The corresponding reaction of the N—H and C—H bonds of amines is relatively unimportant. 

Propargylic (or 2-alkynyl) compounds are derivatives of alkynes. However, Pd-catalyzed reactions of propargylic derivatives, particularly esters and halides, are very different mechanistically from those of simple alkynes, except in a few cases. Therefore, the reactions of propargylic esters and halides are treated in this section separately from those of other alkynes. However, some reactions of propargylic alcohols, which behave similarly to simple alkynes, are treated in Section 6. 

Reaction of alcohols with phosphorus tribromide (Section 4 13) As an alternative to converting alco hols to alkyl bromides with hydrogen bromide the inorganic reagent phosphorus tribromide is some times used... 

The mechanisms of the Fischer esterification and the reactions of alcohols with acyl chlorides and acid anhydrides will be discussed m detail m Chapters 19 and 20 after some fundamental principles of carbonyl group reactivity have been developed For the present it is sufficient to point out that most of the reactions that convert alcohols to esters leave the C—O bond of the alcohol intact... 

In this section, we have started looking at reactions of alcohols. So far in this section, we have focused on the details of familiar reactions (substitution and elimination). Before we leam some new reactions, let s practice the ones that we just reviewed ... 

The reaction of alcohols with CO was catalyzed by Pd compounds, iodides and/or bromides, and amides (or thioamides). Thus, MeOH was carbonylated in the presence of Pd acetate, NiCl2, tV-methylpyrrolidone, Mel, and Lil to give HOAc. AcOH is prepared by the reaction of MeOH with CO in the presence of a catalyst system comprising a Pd compound, an ionic Br or I compound other than HBr or HI, a sulfone or sulfoxide, and, in some cases, a Ni compound and a phosphine oxide or a phosphinic acid.60 Palladium(II) salts catalyze the carbonylation of methyl iodide in methanol to methyl acetate in the presence of an excess of iodide, even without amine or phosphine co-ligands platinum(II) salts are less effective.61 A novel Pd11 complex (13) is a highly efficient catalyst for the carbonylation of organic alcohols and alkenes to carboxylic acids/esters.62... 

Table 6.6 lists some reactions of the electron in water, ammonia, and alcohols. These are not exhaustive, but have been chosen for the sake of analyzing reaction mechanisms. Only three alcohols—methanol, ethanol, and 2-propanol—are included where intercomparison can be effected. On the theoretical side, Marcus (1965a, b) applied his electron transfer concept (Marcus, 1964) to reactions of es. The Russian school simultaneously pursued the topic vigorously (Levich, 1966 Dogonadze et al, 1969 Dogonadze, 1971 Vorotyntsev et al, 1970 see also Schmidt, 1973). Kestner and Logan (1972) pointed out the similarity between the Marcus theory and the theories of the Russian school. The experimental features of eh reactions have been detailed by Hart and Anbar (1970), and a review of various es reactions has been presented by Matheson (1975). Bolton and Freeman (1976) have discussed solvent effects on es reaction rates in water and in alcohols. 

Vardanyan [65,66] discovered the phenomenon of CL in the reaction of peroxyl radicals with the aminyl radical. In the process of liquid-phase oxidation, CL results from the disproportionation reactions of primary and secondary peroxyl radicals, giving rise to trip-let-excited carbonyl compounds (see Chapter 2). The addition of an inhibitor reduces the concentration of peroxyl radicals and, hence, the rate of R02 disproportionation and the intensity of CL. As the inhibitor is consumed in the oxidized hydrocarbon the initial level of CL is recovered. On the other hand, the addition of primary and secondary aromatic amines to chlorobenzene containing some amounts of alcohols, esters, ethers, or water enhances the CL by 1.5 to 7 times [66]. This effect is probably due to the reaction of peroxyl radicals with the aminyl radical, since the addition of phenol to the reaction mixture under these conditions must extinguish CL. Indeed, the fast exchange reaction... 

In addition to their importance in the chemical reactions of alcoholic fermentation, some inorganic components have a significant effect on the stability of wines. Problems frequently are associated with excesses rather than deficiencies of certain inorganic constituents. Generally, excessive levels produce undesirable effects by altering the color, appearance, or taste of the wines (48). An excessive level of inorganic constituents in wines may arise from many sources such as the inherent content in musts, winery equipment, cellars, and vineyard materials. 

This relationship was found to break down for some reactions of yeast alcohol dehydrogenase56 such that (kH/kT)obs > (kD/kT)326. This is unambiguous evidence for quantum mechanical tunneling of the hydrogen. The small mass of the H isotope makes it proportionately more susceptible to tunneling than D or T, and so the classical equation 2.80 underestimates the substitution. The behavior of hydrogen is poised between classical and quantum mechanics.57 58... 

Nicotinamide coenzymes act as intracellular electron carriers to transport reducing equivalents between metabolic intermediates. They are cosubstrates in most of the biological redox reactions of alcohols and carbonyl compounds and also act as cocatalysts with some enzymes. 

A remarkable number of palladium-catalyzed aerobic oxidation reactions of alcohols have been reported to date [15]. Unfortunately, although some progress has been made with heterogeneous Pd catalysts, such as Pd on activated carbon [16], Pd on pumice [17], Pd-hydrotalcite [18], Pd on Ti02 [19] and Pd/SBA-15 [20], most of these systems suffer from low catalytic activities and a limited substrate scope. 

Esterification. Without a doubt, the best known nucleophilic reaction of alcohols is the reaction with organic acids and some derivatives, like acid anhydrides and acid chlorides, to form esters (Reaction XII). 

The first two steps of this mechanism are the same as the elimination reaction. Both reactions are carried out under acidic conditions. The difference is that halide ion serve as good nucleophiles and are present in high concentration. The elimination reaction is carried out using concentrated sulphuric acid and only weak nucleophiles are present (i.e. water) in low concentration. Thus, some elimination may occur and although the reaction of alcohols with HX produces mainly alkyl halide, some alkene byproduct is usually present. 

Although some reactions of electrophilic animation of phosphorus-stabilized anions had already been reported in the literature [5a,d], the first example of such a stereoselective reaction opening access to optically active a-amino phosphonic acids was described in 1992 by Denmark and co-workers [45] and by Jommi and co-workers [46]. Both of these groups used chiral amino alcohols as auxiliaries for diastereo-selective induction in the animating process. Denmark and co-workers chose trisyl azide (2,4,6-triisopropylbenzenesulfonyl azide) as equivalent of NHJ , whereas Jommi and co-workers performed the reaction with DTBAD. 

Some Reactions of Organosilanes with Alcohols and Phenol Catalyzed by Cp2TiCl2/BuLi" ... 

Methylthiomethyl (MTM) ethers. These ethers (h, 109-lltY) ear he prepared by reaction of alcohols with dimethyl sulfide (8 equiv.) and dibenzoyl peroxide (4 equiv.) in CH3CN at 0° (75-90% yield). Excess dimethyl sulfide is required since some of the sulfide is oxidized to dimethyl sulfoxide. 

Many anhydrous metal halides will form alcoholates if the presence of water is avoided during the preparations. The reactions of alcohols with vanadium trichloride were originally thought,1 to produce hexaalcoholates, but subsequent work cast some doubt on this.23 In a recent publication4 it was established that the species formed in solution by treating vanadium trichloride with methanol, ethanol, n- and z-propyl alcohol (1- and 2-propanol), n-, i-, and s-butyl alcohol (1-butanol, 2-mothyl-l-propanol, and 2-butanol), and cyclohexanol are of the type [V(R0H)4C12]C1 in each ease. In some cases the species precipitated from the above solutions have the same structural type,... 

Owing to its powerful Lewis acidity, BF3 is an effective reagent in organic synthesis, for example, promoting the conversion of alcohols and acids to esters, the polymerization of olefins and olefin oxides, and acylations and alkylations (in a manner similar to Friedel-Crafts processes). Mechanistic studies of some reactions of the latter type, such as the ethylation of benzene by QH5F, have shown that the BF3 functions as a scavenger for HF via the formation of HBF4 and thus participates stoichiometrically rather than catalytically. 

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