Nucleophilic substitution alcohols

The only known example of the catalytic nucleophilic aromatic substitution involves the use of Rh(III) complexes (e.g., 40). The first demonstration was made in 1980 [99]. The metal center is so electrophilic that an internal alcohol nucleophile substitutes directly without an added base. 

Sodium/alcohol Nucleophilic substitution with strong nucleophiles Thioethers from halides... 

In stereoselective antitheses of chiral open-chain molecules transformations into cyclic precursors should be tried. The erythro-configurated acetylenic alcohol given below, for example, is disconnected into an acetylene monoanion and a symmetrical oxirane (M. A. Adams, 1979). Since nucleophilic substitution occurs with inversion of configuration this oxirane must be trens-conilgurated its precursor is commercially available trans-2-butene. 

Section 4 9 The potential energy diagrams for separate elementary steps can be merged into a diagram for the overall process The diagram for the reac tion of a secondary or tertiary alcohol with a hydrogen halide is charac terized by two intermediates and three transition states The reaction is classified as a ummolecular nucleophilic substitution, abbreviated as SnI... 

Recall that the term kinetics refers to how the rate of a reaction varies with changes m concentration Consider the nucleophilic substitution m which sodium hydroxide reacts with methyl bromide to form methyl alcohol and sodium bromide... 

Step 3 This step is a fast acid base reaction that follows the nucleophilic substitution Water acts as a base to remove a proton from the alkyloxonium ion to give the observed product of the reaction tert butyl alcohol... 

Additional evidence for carbocation intermediates in certain nucleophilic substitutions comes from observing rearrangements of the kind normally associated with such species For example hydrolysis of the secondary alkyl bromide 2 bromo 3 methylbutane yields the rearranged tertiary alcohol 2 methyl 2 butanol as the only substitution product... 

An advantage that sulfonate esters have over alkyl halides is that their prepara tion from alcohols does not involve any of the bonds to carbon The alcohol oxygen becomes the oxygen that connects the alkyl group to the sulfonyl group Thus the configuration of a sulfonate ester is exactly the same as that of the alcohol from which It was prepared If we wish to study the stereochemistry of nucleophilic substitution m an optically active substrate for example we know that a tosylate ester will have the same configuration and the same optical purity as the alcohol from which it was prepared... 

Section 8 14 Nucleophilic substitution can occur with leaving groups other than halide Alkyl p toluenesulfonates (tosylates) which are prepared from alcohols by reaction with p toulenesulfonyl chloride are often used... 

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... 

Illustrate the stereochemistry associated with unimolecular nucleophilic substitution by con structmg molecular models of cis 4 tert butylcyclohexyl bromide its derived carbocation and the alcohols formed from it by hydrolysis under S l conditions... 

Conversion to p toluenesulfonate es ters (Section 8 14) Alcohols react with p toluenesulfonyl chloride to give p toluenesulfonate esters Sulfo nate esters are reactive substrates for nucleophilic substitution and elimma tion reactions The p toluenesulfo nate group is often abbreviated —OTs... 

Nucleophilic Reactions. Useful nucleophilic substitutions of halothiophenes are readily achieved in copper-mediated reactions. Of particular note is the ready conversion of 3-bromoderivatives to the corresponding 3-chloroderivatives with copper(I)chloride in hot /V, /V- dim ethyl form am i de (26). High yields of alkoxythiophenes are obtained from bromo- and iodothiophenes on reaction with sodium alkoxide in the appropriate alcohol, and catalyzed by copper(II) oxide, a trace of potassium iodide, and in more recent years a phase-transfer catalyst (27). 

Sulfonate esters are especially useful substrates in nucleophilic substitution reactions used in synthesis. They have a high level of reactivity, and, unlike alkyl halides, they can be prepared from alcohols by reactions that do not directly involve bonds to the carbon atom imdeigoing substitution. The latter aspect is particularly important in cases in which the stereochemical and structural integrity of the reactant must be maintained. Sulfonate esters are usually prepared by reaction of an alcohol with a sulfonyl halide in the presence of pyridine ... 

A poor leaving group can be made more reactive by coordination to an electrophilic species. Hydroxide is a very poor leaving group. Normally, alcohols therefore do not undergo direct nucleophilic substitution. It has been estimated that the reaction... 

There are alternatives to the addition-elimination mechanism for nucleophilic substitution of acyl chlorides. Certain acyl chlorides are known to react with alcohols by a dissociative mechanism in which acylium ions are intermediates. This mechanism is observed with aroyl halides having electron-releasing substituents. Other acyl halides show reactivity indicative of mixed or borderline mechanisms. The existence of the SnI-like dissociative mechanism reflects the relative stability of acylium ions. 

We first encountered nucleophilic substitution in Chapter 4, in the reaction of alcohols with hydrogen halides to fonn alkyl halides. Now we ll see how alkyl halides can themselves be converted to other classes of organic compounds by nucleophilic substitution. 

Two kinds of starting materials have been examined in nucleophilic substitution reactions to this point. In Chapter 4 we saw that alcohols can be converted to alkyl halides by reaction with hydrogen halides and pointed out that this process is a nucleophilic substitution taking place on the protonated fonm of the alcohol, with water serving as the... 

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