Reactions of alcohols

Alcohols are important organic compounds because the hydroxyl group is easily converted to almost any other functional group. In Chapter 10, we studied reactions that form alcohols. In this chapter, we seek to understand how alcohols react and which reagents are best for converting them to other kinds of compounds. Table 11-1 summarizes the types of reactions alcohols undergo and the products that result. 

Oxidation States of Alcohols and Related Functional Groups 

Oxidation of alcohols leads to ketones, aldehydes, and carboxylic acids. These functional groups, in turn, undergo a wide variety of additional reactions. For these reasons, alcohol oxidations are some of the most common organic reactions. 

NEITHER addition or loss of H , H2O, HX, etc. is neither an oxidation nor a reduction. 

Oxidation states of alcohols. An alcohol is more oxidized than an alkane, yet less oxidized than carbonyl compounds such as ketones, aldehydes, and acids. Oxidation of a primary alcohol leads to an aldehyde, and further oxidation leads to an acid. Secondary alcohols are oxidized to ketones. Tertiary alcohols cannot be oxidized without breaking carbon-carbon bonds. 

Alcohols undergo reactions in which several different bonds can break, depending on experimental conditions. In some reactions, the O—H bond breaks in others, the C—O bond breaks. The C—H bond on the carbon atom bearing the hydroxyl group or the C—H bond on the carbon atom adjacent to that carbon atom bearing the OH group also react under some conditions. We will divide our discussion of the reactions of alcohols into four classes based on the bonds that break. We wiU discuss the first three classes of reactions in this chapter. We will discuss the fourth in Chapter 15 when we expand our treatment of alcohol reactions and synthesis. 

The oxygen-hydrogen bond breaks in an acid-base reaction. 

The carbon-oxygen bond breaks in a nucleophilic substimtion reaction. 

Starting from an ester, the only possibility is addition of methylmagnesiiim bromide to an ester of butanoic acid, such as methyl butanoate. 

Problem 17.9 Show the products obtained from addition of methylmagnesiiim bromide to the following compounds  

Problem 17.11 Use the reaction of a Grignard reagent with a carbonyl compound to syntnesize the 

Interactive to use a web-based palette to predict products from a variety of reactions involving alcohols. 

We ve already seen sev eral reactions of alcohols—their conversion into alkvl halides and tosylates in Section L0.6 and their dehydration to give alkenes in Section 7.1—although without mechanistic details. Let s now look at tho.se details. 

Problem 17.10 Use a Grignard reaction to jjrepare the following alcohols  

Thomson v Click Organic WeVe already seen several reactions of alcohols—their conversion into alkyl 

25° C (see text section 10-11C) and therefore has AG 0. This makes the question of kinetics academic—a reaction that cannot proceed must be uselessly slow. 

A5 0 since one molecule is converted to two therefore,-TA5 0. At low temperature (25° C), A// dominates because T is so small, so AG 0. At a high enough temperature, the -TA5 term will begin to overwhelm A//, and AG will become negative. For the reaction in question, this must be the case at 300° C. 

Understand that other choices are legitimate for example, Swem oxidation works about as well as PCC in the preparation of aldehydes, and Collins reagent or PCC will oxidize a 2° alcohol to a ketone as well as chromic acid. If you have a question about the appropriateness of a reagent you choose, consult the table in the text before Problem 11-2. 

11-7 A chronic alcoholic has induced more ADH enzyme to be present to handle large amounts of imbibed ethanol, so requires more ethanol antidote molecules to act as a competitive inhibitor to tie up the extra enzyme molecules. 

1) chromic acid—distinguishes 3° alcohol from either 1° or 2° 

We ve already seen one general reaction of alcohols—their conversion to alkyl halides (Section 12.3). Tertiary alcohols react with HGl and HBr by an SnI mechanism through a carhocation intermediate. Primary and secondary alcohols react with SOCI2 and PBra by an Sn2 mechanism through backside attack on a chlorosulfite or dibromophosphite intermediate. 

A second important reaction of alcohols, both in the laboratory and in biological pathways, is their dehydration to give alkenes. One method that works particularly well for tertiary alcohols is the acid-catalyzed reaction, which 

O Two electrons from the oxygen atom bond to H, yielding a protonated alcohol intermediate. 

ACTIVE FIGURE 13.4 MECHANISM Mechanism of the acid-catalyzed dehydration of a tertiary alcohol to yield an alkene. The process is an El reaction and involves a carbocation intermediate. Co to this book s student companion site at www.cengage.com/chemistry/ mcmurry to explore an interactive version of this figure. 

CHAPTER 13 ALCOHOLS, PHENOLS, AND THIOLS ETHERS AND SULFIDES 

Predict the products of the reactions of alcohols with oxidants, hydrohalic acids, dehydrating agents, and alkali metals. 

Propose mechanisms to explain alcohol reactions such as dehydration and oxidation. 

Plan multistep syntheses using alcohols as starting materials and intermediates. 

STRATEGY AND ANSWER We recognize that synthesis by path (a) would require a Markovnikov addition of water to the alkene. So, we could use either acid-catalyzed hydration or oxymercuration-demercuration. 

Synthesis by path (b) requires an anti-Markovnikov addition, so we would choose hydroboration-oxidation. 

The following reaction does not produce the product shown. 

The reactions of alcohols have mainly to do with the following  

Our understanding of the reactions of alcohols will be aided by an initial examination of the electron distribution in the alcohol functional group and of how this distribution affects its reactivity. The oxygen atom of an alcohol polarizes both the C—O bond and the O—H bond of an alcohol  

Tertiary alcohols react with either HCl or HBr at 0 °C by an SnI mechanism through a carbocation intermediate. Primary and secondary alcohols are much more resistant to acid, however, and are best converted into halides by treatment with either SOCI2 or PBrs through an Sn2 mechanism. 

The reaction of a tertiary alcohol with HX takes place by an SnI mechanism when acid protonates the hydroxyl oxygen atom, water is expelled to generate a carbocation, and the cation reacts with nucleophilic halide ion to give the alkyl halide product. 

Alcohols react with p-toluenesulfonyl chloride (tosyl chloride, p-TosCl) in pyridine solution to yield alkyl tosylates, ROTos (Section 11.1). Only the O-H bond of the alcohol is broken in this reaction the C O bond remains intact, so no change of configuration occurs if the oxygen is attached to a chirality center. 

The resultant alkyl tosylates behave much like alkyl halides, undergoing both S jl and Sn2 substitution reactions. 

Amongst the new deactivated chromium(VI) reagents which have been described are 3- and 4-carboxypyridinium dichromate, derived from nicotinic and isonicotinlc acid respectively, which oxidize benzylic and allylic alcohols, and a pyridinium chlorochromate- 

Primary and secondary alcohols are efficiently oxidized to aldehydes or ketones under solid-liquid phase-transfer conditions using 

Fremy s salt will oxidize benzylic and furyl alcohols under 

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Another method for the hydrogenoiysis of aryl bromides and iodides is to use MeONa[696], The removal of chlorine and bromine from benzene rings is possible with MeOH under basic conditions by use of dippp as a ligand[697]. The reduction is explained by the formation of the phenylpalladium methoxide 812, which undergoes elimination of /i-hydrogen to form benzene, and MeOH is oxidized to formaldehyde. Based on this mechanistic consideration, reaction of alcohols with aryl halides has another application. For example, cyclohex-anol (813) is oxidized smoothly to cyclohexanone with bromobenzene under basic conditions[698]. 

Mechanism of the Reaction of Alcohols with Hydrogen Halides... 

MECHANISM OF THE REACTION OF ALCOHOLS WITH HYDROGEN HALIDES... 

One important experimental fact is that the rate of reaction of alcohols with hydro gen halides increases m the order methyl < primary < secondary < tertiary This reac tivity order parallels the carbocation stability order and is readily accommodated by the mechanism we have outlined... 

Reactions of alcohols with hydrogen halides (Section... 

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... 

Zaitsev s rule as applied to the acid catalyzed dehydration of alcohols is now more often expressed in a different way elimination reactions of alcohols yield the most highly substituted alkene as the major product Because as was discussed in Section 5 6 the most highly substituted alkene is also normally the most stable one Zaitsev s rule is sometimes expressed as a preference for predominant formation of the most stable alkene that could arise by elimination... 

The dehydration of alcohols resembles the reaction of alcohols with hydrogen halides (Section 4 7) m two important ways... 

These common features suggest that carbocations are key intermediates m alcohol dehydra tions just as they are m the reaction of alcohols with hydrogen halides Figure 5 6 portrays a three step mechanism for the acid catalyzed dehydration of tert butyl alcohol Steps 1 and 2 describe the generation of tert butyl cation by a process similar to that which led to its for matron as an intermediate m the reaction of tert butyl alcohol with hydrogen chloride... 

Preparation of Alkenes by Elimination Reactions of Alcohols and Alkyl Halides... 

We have seen this situation before m the reaction of alcohols with hydrogen halides (8ection 4 11) m the acid catalyzed dehydration of alcohols (8ection 5 12) and m the conversion of alkyl halides to alkenes by the El mechanism (8ection 5 17) As m these other reactions an electronic effect specifically the stabilization of the carbocation intermediate by alkyl substituents is the decisive factor The more stable the carbo cation the faster it is formed... 

The principles developed in this chapter can be applied to a more detailed examination of the reaction of alcohols with hydrogen halides than was possible when this reaction was first introduced m Chapter 4... 

The reactions of alcohols with hydrogen halides to give alkyl halides (Chapter 4) are nucleophilic substitution reactions of alkyloxonium ions m which water is the leaving group Primary alcohols react by an 8 2 like displacement of water from the alkyloxonium ion by halide Sec ondary and tertiary alcohols give alkyloxonium ions which form carbo cations m an S l like process Rearrangements are possible with secondary alcohols and substitution takes place with predominant but not complete inversion of configuration... 

Alcohols are versatile starting materials for the preparation of a variety of organic func tional groups Several reactions of alcohols have already been seen m earlier chapters and are summarized m Table 15 2 The remaining sections of this chapter add to the list... 

Summary of Reactions of Alcohols Discussed in Earlier Chapters... 

Esters are also formed by the reaction of alcohols with acyl chlorides... 

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... 

The reaction of alcohols with acyl chlorides is analogous to their reaction with p toluenesulfonyl chloride described earlier (Section 8 14 and Table 15 2) In those reactions a p toluene sulfonate ester was formed by displacement of chloride from the sulfonyl group by the oxygen of the alcohol Carboxylic esters arise by displacement of chlonde from a carbonyl group by the alcohol oxygen... 

Although the term ester used without a modifier is normally taken to mean an ester of a carboxylic acid alcohols can react with inorganic acids m a process similar to the Fis cher esterification The products are esters of inorganic acids For example alkyl nitrates are esters formed by the reaction of alcohols with nitric acid... 

Section 15 6 Table 15 2 summarizes reactions of alcohols that were introduced m ear her chapters... 

Steps 4-5 Conversion of hemiacetal to carbocation These steps are analogous to the formation of carbocations m acid catalyzed reactions of alcohols... 

Chloroacetate esters are usually made by removing water from a mixture of chloroacetic acid and the corresponding alcohol. Reaction of alcohol with chloroacetyl chloride is an anhydrous process which Hberates HCl. Chloroacetic acid will react with olefins in the presence of a catalyst to yield chloroacetate esters. Dichloroacetic and trichloroacetic acid esters are also known. These esters are usehil in synthesis. They are more reactive than the parent acids. Ethyl chloroacetate can be converted to sodium fluoroacetate by reaction with potassium fluoride (see Fluorine compounds, organic). Both methyl and ethyl chloroacetate are used as agricultural and pharmaceutical intermediates, specialty solvents, flavors, and fragrances. Methyl chloroacetate and P ionone undergo a Dar2ens reaction to form an intermediate in the synthesis of Vitamin A. Reaction of methyl chloroacetate with ammonia produces chloroacetamide [79-07-2] C2H ClNO (53). 

DiaLkyl peroxides may be prepared by reaction of alcohols or alkyl trifluoromethanesulfonates with organomineral peroxides of siUcon, tin, and germanium (44,108), where Q = Sn and Ge ... 

Lower aHphatic amines can be prepared by a variety of methods, using many different types of raw materials. By far the largest commercial appHcations involve the reaction of alcohol with ammonia to form the corresponding amines. Other methods are employed depending on the particular amine desired, raw material availabiHty, plant economics, and the abiHty to seU co-products. The foUowing manufacturing methods are used commercially to produce the lower aLkylamines. Table 5 gives plant and capacity information for these methods. 

The amyl alcohols undergo the typical reactions of alcohols which are characterized by cleavage at either the oxygen—hydrogen or carbon—oxygen bonds. 

Alkyl carbamates (urethanes) ate formed from reaction of alcohols with isocyanic acid or urea (see Urettpane polymers). 

Reduction of Alcohols or Ketones. The reaction of alcohols and ketones with chlorine and base to give chloroform is well known (30). 

The most important discovery in dyeing cellulose with reactive dyes was the appHcation of Schotten-Baumaun principles. Reaction of alcohols proceeds more readily and completely in the presence of dilute alkali, and the cellulose anion (cell- O ) is considerably more nucleophilic than is the hydroxide ion. Thus the fixation reaction (eq. 1) competes favorably with hydrolysis of the dye (eq. 2). 

The reaction of alcohols and acid chlorides in the presence of magnesium has been described (68). With primary and secondary alcohols the reaction is very smooth, and affords high and sometimes quantitative yields. Difficulty esteritiable hydroxy compounds such as tertiary alcohols and phenols can be esteritied by this method. The reaction carried out in ether or benzene is usually very vigorous with evolution of hydrogen. 

Kinetic studies of the reaction of alcohols with acyl chlorides in polar solvents in the absence of basic catalysts generally reveal terms both first-order and second-order in alcohol. Transition states in which the second alcohol molecule acts as a proton acceptor have been proposed ... 

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