CHAPTER 9 Further Reactions of Alcohols and the Chemistry of Ethers

A variety of reaction modes are available to alcohols. 2

Reactions of Alcohols with Base: Alkoxides 9-1 Strong bases are needed to deprotonate alcohols completely. Base strength must be stronger than that of the alkoxide.

Alkali metals also deprotonate alcohols, but by reduction of H +. Less Vigorous: Relative reactivities: Vigorous: 4

Uses for alkoxides: Hindered alkoxides E 2 reactions with haloalkanes to form alkenes. Less hindered alkoxides S N2 reactions with haloalkanes to form ethers.

Reactions of Alcohols with Strong Acids: Alkyloxonium Ions in Substitution and Elimination Reactions of Alcohols 9-2 Water has a high pK a (15.7) which means that its conjugate base, OH - is an exceedingly poor leaving group. The –OH group of an alcohol must be converted into a better leaving group for alcohols to participate in substitution or elimination reactions. 6 Protonation of the hydroxy substituent of an alcohol to form an alkyloxonium ion converts the –OH from the poor leaving group, OH -, to the good leaving group, H 2 O.

Primary bromoalkanes and iodoalkanes can be prepared by the reaction with HBr and HI. Chloroalkanes cannot be prepared by this method because Cl - is too poor a nucleophile.

Secondary and tertiary alcohols undergo carbocation reactions with acids: S N 1 and E1. Primary alkyloxonium ions undergo only S N 2 reactions with acid. Their carbocation transition state energies are too high to allow S N 1 and E1 reactions under ordinary laboratory conditions. Secondary and tertiary alkyloxonium ions lose water when treated with acid to form a carbocation. 8

When good nucleophiles are present, the S N 1 mechanism predominates. Here the tertiary carbocation is generated at a relatively low temperature, which prevents the competing E 1 reaction. At higher temperatures, or in the absence of good nucleophiles, elimination becomes dominant.

Secondary alcohols show complex behavior when treated with HX, following S N 2, S N 1, and E1 pathways. Relatively hindered (compared to primary alcohols): Retarded S N 2 reactivity Slow to form carbocations (compared to tertiary alcohols): Retarded S N 1 reactivity. 10

E1 reactions of alcohols (dehydrations) result in the formation of alkenes. Non-nucleophilic acids, such as H 3 PO 4 or H 2 SO 4, are used in this case, rather than the nucleophilic acids, HBr and HI. Dehydrations of tertiary alcohols often occur just above room temperature.

Summary 12

Carbocation Rearrangements9-3 Hydride shifts give new S N 1 products. Treatment of substituted secondary alcohols produces unexpected results:

Rearrangement of an initial secondary carbocation to the more stable tertiary carbocation by a hydride shift results in a rearranged product. 14

Hydride shifts are very fast (faster than S N 1 or E1) which is partially due to hyperconjugation in the carbocation weakening the C-H bond):

1 o carbocations are too unstable to be formed by rearrangement. 2 o or 3 o carbocations equilibrate readily, leading to a mixture of products when trapped by a nucleophile. Carbocation rearrangement takes place regardless of the precursor leading to the carbocation. 16

Carbocation rearrangements also give new E1 products. Under conditions favoring elimination (elevated temperatures and non-nucleophilic media), carbocations can also rearrange to give rearranged products.

Other carbocation rearrangements are due to alkyl shifts. Alkyl shifts, rather than hydride shifts, can occur when a carbocation lacks a suitable secondary or tertiary hydrogen next to the positively charged carbon. 18

Alkyl and hydride shifts are faster when leading to a tertiary carbocation than when leading to a secondary carbocation. In the previous haloalkane rearrangement, movement of an ethyl group rather than a hydride would result in a secondary rather than a tertiary carbocation. Exceptions to this general rule can occur as a result of electronic stabilization or steric relief.

Primary alcohols may undergo rearrangement. Alkyl and hydride shifts to primary carbons bearing leaving groups can occur without the formation of primary carbocations. Steric hindrance interferes with direct attack by the bromide ion. Instead, water leaves at the same time as the methyl group migrates, bypassing the formation of a primary carbocation. 20

Organic and Inorganic Esters from Alcohols9-4 Organic esters are derivatives of carboxylic acids. Inorganic esters are the analogous derivatives of inorganic acids.

Organic and Inorganic Esters from Alcohols9-4 Alcohols react with carboxylic acids to give organic esters. Esterification is the reaction of alcohols with carboxylic acids in the presence of catalytic amounts of a strong inorganic acid (H 2 SO 4 or HCl) which yields esters and water. This is an equilibrium process which can be shifted in either direction. 22

Haloalkanes can be made from alcohols through inorganic esters. As an alternative to the acid-catalyzed conversions of alcohols into haloalkanes, a number of inorganic reagents can convert the alcoholic hydroxyl group into a good leaving group under milder conditions. Reaction of PBr 3 with a secondary alcohol yields a bromoalkane and phosphorous acid (all three bromine atoms can be utilized).

Iodoalkanes can be prepared using PI 3, which, because of its reactivity, is generated from red phosphorous and iodine in the reaction mixture itself. 24

Chloroalkanes are commonly prepared using thionyl chloride by warming an alcohol in its presence. An amine such as triethyl amine is usually added to consume the generated HCl.

Alkyl sulfonates are versatile substrates for substitution reactions. Alkyl sulfonates are often crystalline solids and can be isolated and purified before further reaction. Alkyl sulfonates are excellent leaving groups, generated by the reaction of an alcohol with sulfonyl chloride. Pyridine or a tertiary amine is used to remove the HCl formed. 26

The sulfonate group can be displaced by halide ions (particularly in primary and secondary systems). The sulfonate group can also be displaced by any good nucleophile, not just by halide ions as was the case for hydrogen, phosphorous, and thionyl halides.

Names and Physical Properties of Ethers9-5 In the IUPAC system, ethers are alkoxyalkanes. IUPAC: Ethers are alkanes bearing an alkoxy substituent. The larger substituent is the stem and the smaller substituent is the alkoxy group (methoxyethane). Common Names: The names of the two alkyl groups are followed by the word “ether” (ethylmethylether). 28

Except for strained cyclical derivatives, ethers are fairly unreactive and are often used as solvents in organic reactions. Cyclic ethers are members of cycloalkanes called heterocycles: one or more carbon atoms have been replaced by a heteroatom. Cyclic ethers’ names are based on the oxacycloalkane stem: Oxacyclopropane (oxiranes, epoxides, ethylene oxides) Oxacyclobutane, Oxacyclopentane (tetrahydrofurans) Oxacyclohexanes (tetrahydropyrans) Ring numbering starts on the oxygen atom.

Cyclic polyethers based on the 1,2-ethanediol unit are called crown ethers. The crown ether 18-crown-6 contains 18 total atoms and 6 oxygen atoms. Note that the inside of the ring is electron rich. 30

Simple alkoxyalkanes have the same molecular formula as the equivalent alkanols, C n H 2n+2 O, but have much lower boiling points due to the absence of hydrogen bonding. The smaller alkoxyalkanes are water soluble, however solubility decreases with increasing hydrocarbon size. Methoxymethane — completely water soluble Ethoxyethane — 10% aqueous solution

Polyethers solvate metal ions: crown ethers and ionophores. The size of the central cavity can be tailored to selectively bind cations of differing ionic radii. 32 Crown ethers can render salts soluble in organic solvents by chelating the metal cations. This allows reagents such as KMnO 4 to act as an oxidizing agent in the organic solvents.

Three-dimensional analogs of crown ethers are polyethers called cryptands. These are highly selective in alkali and other metal cation binding.