Reactions of Alcohols Substitution and Elimination

Many phenols and their derivatives exhibit topical antifungal properties. These agents are believed to interfere with the cell membrane function of fungi. The following are just a few examples. 

These compounds, as well as many others, are used in the treatment of athlete s foot, jock itch, and ringworm. Tolnaftate is the active ingredient in Odor Eaters, and Desenex . 

As seen in Section 7.5, tertiary alcohols will undergo a substitution reaction when treated with 

We saw that this reaction proceeds via an Sjvjl mechanism. 

Recall that an Sjvjl mechanism has two core steps (loss of leaving group and nucleophilic attack). When the starting material is an alcohol, we saw that an additional step is required in order to protonate the hydroxyl group first. This reaction proceeds via a carbocation intermediate and is therefore most appropriate for tertiary alcohols. Secondary alcohols undergo S],jl more slowly, and primary alcohols will not undergo S],jl at an appreciable rate. When dealing with a primary alcohol, an Sj. 2 pathway is required in order to convert an alcohol into an alkyl halide. 

Now that we have seen how to make alcohols, we will focus our attention on reactions of alcohols. Let s start by reviewing reactions that we have already seen substitution and elimination. Let s begin our review with elimination reactions first. We have seen two types of elimination reactions El an E2. 

To eliminate an OH group under El conditions, we need acidic conditions  

In the last step, tert-butoxide was used to favor elimination over substitution (see Section 10.10). hi summary, we have seen that we can use either an El process or an E2 process to convert an alcohol into an alkene. 

If we want to perform a substitution reaction with an alcohol, we have the same issue that we had when we explored elimination reactions a few moments ago—the OH group is not a good leaving group. So, we must convert the OH into a better leaving group. There are several ways to do that for substitution reactions. We will look at four different ways  

1) Via an Si l process. With a tertiary alcohol, we can use an SnI process. We simply use an acid to protonate the OH group, converting it into an excellent leaving group. The first two steps of this reaction are identical to the El process that we just saw  

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Alkyl halides are encountered less frequently than their oxygen-containing relatives alcohols and ethers, but some of the kinds of reactions they undergo—nucleophilic substitutions and eliminations—are encountered frequently. Thus, alkyl halide chemistry acts as a relatively simple model for many mechanistically similar but structurally more complex reactions found in biornolecules. We ll begin in this chapter with a look at how to name and prepare alkyl halides, and we ll see several of their reactions. Then in the following chapter, we ll make a detailed study of the substitution and elimination reactions of alkyl halides—two of the most important and well-studied reaction types in organic chemistry. 

Part I. The Reactions of Alcohols, Enols, and Phenols Oxidation, Reduction, Substitution, Addition, Elimination, and Rearrangement Part II. Ethers... 

In Chapter 9, we introduced the basic principles of nucleophilic substitution and elimination reactions. We focused almost entirely upon the reactions of haloalkanes and alcohols. In this chapter, we will expand upon these reactions and consider a much wider range of nucleophiles, leaving groups, substrates, solvents, and their effects on nucleophilic substitution and elimination reactions. We will ask ... 

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 ... 

It was expected that values of ks/kp for partitioning of [1+] could be obtained from the yields of the products of acid-catalyzed reactions of [l]-OH and [2]. However, significantly different relative yields of these products are obtained from the perchloric acid-catalyzed reactions of [l]-OH and [2] in several mixed alcohol/water solvents.21 This demonstrates that the nucleophilic substitution and elimination reactions of these two substrates do not proceed through identical tertiary carbocation intermediates (Scheme 4). The observed... 

In this section, you were introduced to some of the main types of organic reactions addition, substitution, and elimination reactions oxidation and reduction and condensation and hydrolysis reactions. In the next section, you will take a close look at each type of reaction. You will find out how organic compounds, such as alcohols and carboxylic acids, can react in several different ways. 

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

We begin by bringing you up to speed on mechanisms and reminding you how to push electrons around with those curved arrows. We jog your memory with a discussion of substitution and elimination reactions and their mechanisms, in addition to free radical reactions. Next you review the structure, nomenclature, synthesis, and reactions of alcohols and ethers, and then you get to tackle conjugated unsaturated systems. Finally, we remind you of spectroscopic techniques, from the IR fingerprints to NMR shifts. The review in this part moves at a pretty fast pace, but we re sure you can keep up. 

The reaction occurs via a carbocation intermediate. Therefore, it is possible to form both substitution and elimination products. Secondary alcohols with branching on the [f-carbon give rearranged products. The temperature must be kept low to avoid the formation of El product. 

In acidic solution, an alcohol is in equilibrium with its protonated form Protonation converts the hydroxyl group from a poor leaving group (-OH) to a good leaving group (H20). Once the alcohol is protonated, all the usual substitution and elimination reactions are feasible, depending on the structure (1°, 2°, 3°) of the alcohol. 

The ability of fluoro-2 -phosphanes to transform silyl ethers into fluorides was first observed during a study of the reactions of phosphorus pentafluoride and its derivatives R PF5 (n = 1, 2, 3 R = hydrocarbon group) with trimethylsilyl ethers. Subsequently, this reaction was proposed as a new method for the preparation of C-F compounds from silyl ethers or silicic acid esters with fluoro-A -phosphanes. Pentafluorophenyl-substituted fluoro-A -phos-phanes were found to react similarily, Other workers found that tctrafluoro(phenyl)-A -phos-phane. which was chosen as the most convenient reagent with regard to reactivity and stability, gave considerable amounts of elimination products, especially with primary and cyclic alcohols. Good yields of fluorinated products are obtained when stable carbocations can be formed at the site of substitution, such as in tertiary alcohols, but 2-phcnylethanol. benzyl alcohol and diphcnylmethanol, on the other hand, give only poor yields of fluorinated products ethers and polymers are the main products. ... 

Betylates. Ammonioalkanesulfonate esters (1) have been given the trivial name betylates because they form betaines on substitution or elimination. They are prepared by reaction of alcohols with ethenesulfonyl chloride and trimethylamine and then with dimethylamine and CH3X. (equation I). ... 

Unlike many families of molecules, the reactions of alcohols do not fit neatly into a single reaction class. In Chapter 9, we discuss only the substitution and P elimination reactions of alcohols. Alcohols are also key starting materials in oxidation reactions (Chapter 12), and their polar O - H bond makes them more acidic than many other organic compounds, a feature we will explore in Chapter 19. 

Summary Nucleophilic substitution and p elimination reactions of alcohols... 

The reactions of carboxylic acids and substituted acids with the titanous-peroxide system have been studied by Dixon et al. (1964). The acids are less reactive than alcohols for example, whereas the. signals ascribed to the oxidizing radicals are eliminated by an approximately O 1m solution of methanol, acetic acid is required in about 2 m concentration the radicals resulting are -CHg. CO2H and, in lower concentration, CH3. The main lines in the spectrum from propionic acid are those of the radical formed by abstraction from the ]8-carbon atom. 

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