Reactions of Alcohols, Ethers and Oxiranes

The most significant reactions in organic chemistry of the functional groups alcohols, ethers and oxiranes are described below.

reacciones de alcoholes eteres oxiranos epoxidos

Dehydration of alcohols

Alcohols in the presence of mineral acids suh as H2SO4 o H3PO4 they give alkenes by loss of a water molecule. The order of reactivity of alcohol is:

tertiary (3º) > secondary (2º) > primary (1º)

The process is regioselective on secondary and tertiary alcohols.

The reactions obey Zaitsev's rule which states "the more highly substituted alkene is the more likely product formed in an elimination reaction".

The explanation lies in the fact that this is the most thermodynamically stable alkene.

reacciones de alcoholes eteres oxiranos epoxidos deshidratacion de alcoholes regla de Zaitsev

Tertiary and secondary alcohols react by a E2 mechanism, whereas in primary alcohols it is of the E1 type, due to the instability of the hypothetical primary carbocation that would occur.

Sometimes alkenes are produced from the transposition of carbocations (as reaction intermediates). HX-type acids are not used in these reactions due to the nucleophilic character of the anion, thus avoiding substitution reactions.

Conversion of alcohols to ethers

Conversion of alcohols to ethers in acidic media

Primary alcohols are transformed into ethers by acid catalysis (heating).

reacciones de alcoholes eteres oxiranos epoxidos conversion de alcoholes en eteres en medio acido

Generally, sulfuric acid is used. The reaction starts by protonation of the hydroxyl of the alcohol.

reacciones de alcoholes eteres oxiranos epoxidos conversion de alcoholes en eteres en medio acido
It is limited to the preparation of symmetric ethers from primary alcohols.

Under these conditions secondary and tertiary alcohols preferentially give alkenes.

Conversion of alcohols to ethers by means of alkoxides (Williamson's synthesis)

Treatment of an alcohol with a suitable base generates an alkoxide which by nucleophilic displacement on an alkyl halide produces an ether. The base used with the alcohol is Nao.

The alcohol can be primary, secondary or even tertiary. However, the alkyl halide must be methyl or primary since the mechanism of this reaction is SN2 type

reacciones de alcoholes eteres oxiranos epoxidos conversion de alcoholes en eteres mediante alcoxidos sintesis de Williamson
In secondary and tertiary halides the elimination reaction predominates to give alkenes, so the procedure is not applicable.

If this reaction is performed intramolecularly, it gives rise to cyclic ethers, e.g., a halohydrin forms the corresponding epoxide.

reacciones de alcoholes eteres oxiranos epoxidos conversion de alcoholes en eteres mediante alcoxidos sintesis de Williamson

Conversion of alcohols to silyl ethers

The alcohols react with trialkylsilyl chlorides to give silyl esters, in the presence of a tertiary amine such as triethylamine, pyridine or imidazole which acts as a base and neutralizes the HCl released.

These compounds are stable under a wide variety of conditions, such as in the presence of oxidants, reductants, or acids and bases in aprotic media.

They are easily cleaved with fluoride ion in the form of tetralkyl ammonium salt. Silyl derivatives (TMSO-, TESO-, TIPSO- or TBDMSO-), are used as protective group of hydroxyls in many syntheses.

Conversion of alcohols to esters

Carboxylic acid esters (Fischer's esterification)

Alcohols with carboxylic acids react to give esters in the presence of a mineral acid.

reacciones de alcoholes eteres oxiranos epoxidos conversion de alcoholes en esteres esterificacion de Fischer

Esters of sulfonic acids

The reaction of an alcohol with sulfonic acids leads to the formation of a sulfonic ester.

reacciones de alcoholes eteres oxiranos epoxidos conversion de alcoholes en esteres de acidos sulfonicos

Conversion of alcohols to haloalkanes

Reactions of alcohols with HX

Alcohols react with HX to yield alkyl halides.

reacciones de alcoholes eteres oxiranos epoxidos conversion de alcoholes en haloalcanos

The order of reactivity for hydrogen halide is HI > HBr > HCl > HF, while for alcohols it is:

tertiary (3º) > secondary (2º) > primary (1º) > methyl

The reaction generally proceeds by an SN1-type mechanism, so that in some cases transpositions in the intermediate carbocations may occur.

For primary alcohols or methanol the reaction mechanism is of the SN2 type.

Primary and secondary alcohols do not react with HCl at the rate necessary to give good yields. Secondary alcohols (2º) that do not react with HCl, do react when a solution of ZnCl2 in HCl concentrate is used (reactivo de Lucas).

With HBr, in secondary alcohols acceptable or good yields are obtained if the temperature is raised. The best result is obtained with tertiary alcohols.

Reactions of alcohols with thionyl chloride (SOCl2)

Alcohols react with thionyl chloride (SOCl2) to give alkyl chlorides and as by-products, sulfur dioxide (SO2) and hydrogen chloride HCl.

reacciones de alcoholes eteres oxiranos epoxidos reacciones de alcoholes con cloruro de tionilo

Esta reacción se aplica, fundamentalmente, en alcoholes primarios y secundarios, y transcurre mediante un intermedio clorosulfito (R-O-SOCl).

Depending on whether or not a base such as pyridine is used, the reaction proceeds with inversion or with retention of the configuration.

reacciones de alcoholes eteres oxiranos epoxidos reacciones de alcoholes con cloruro de tionilo

With base, a sufficient concentration of Cl (in the form of pyridinium chloride) is available for chlorosulfite displacement to occur by an SN2 mechanism. If there is no base, the reaction proceeds with retention of the configuration by an intramolecular process (syn).

Reaction of alcohols with phosphorus trichloride or tribromide

Los alcoholes se transforman en haluros de alquilo con tricloruro o tribromuro de fósforo. The reaction occurs preferentially in primary alcohols and the mechanism is SN2. In secondary alcohols SN1 competes and skeletal transposition products are obtained. One mole of PX3 reacts with three moles of alcohol.

reacciones de alcoholes eteres oxiranos epoxidos reacciones de alcoholes con tricloruro o tribromuro de fosforo

Reaction of alcohols with CX (Appel reaction).

The alcohols react with tetrahalomethanes (X = Cl or Br) and triphenylphosphine to give, in good yields, the corresponding alkyl halide with configuration inversion. The reaction conditions are mild and compatible with a multitude of functions.

reacciones de alcoholes eteres oxiranos epoxidos reaccion de appel

Table 1: Summary of the transformation of alcohols into halogenated derivatives.
SubstrateStereochemistry / mechanismReagent / reaction conditions
Alcohol 2º and mainly 3ºRacemization / SN1XH
Alcohol 1ºInversion of configuration / SN2PX3 / in the presence of base
Alcohol 1º and 2ºSOCl2 / in the presence of base
CX4 / PPh3
Retention of configuration / SNiSOCl2 / in the absence of base

Deoxygenation of alcohols (reduction)

By means of thiocarbonyl derivatives (Barton-McCombie reaction)

Normally, alcohols cannot be directly transformed into the corresponding saturated compounds. Generally, it is necessary to carry out the transformation in two steps.

In the first instance an alcohol derivative is obtained, and on this derivative the transformation into the saturated compound takes place.

In this deoxygenation method an alcohol is transformed into thiocarbonyl derivative, which subsequently reacts with tri-butyltin hydride (Bu3SnH) by a radical process.

reacciones de alcoholes eteres oxiranos epoxidos reaccion de barton-mccombie

Sulfonate-mediated reactions

The alcohol is first transformed into a sulfonate (tosylate or mesylate) which, by treatment with LiAlH4 is transformed into the saturated compound.

reacciones de alcoholes eteres oxiranos epoxidos reaccion mediante sulfonato

The reaction proceeds in good yields from primary (1º) and secondary (2º) alcohols.

Oxidation of alcohols

Alcohols can be oxidized by the reactions shown in the general scheme. For oxidation to occur, at least one hydrogen atom must be present on the carbon to be oxidized (1º primary or 2º secondary alcohol), so that a C=O double bond can be formed. Therefore, tertiary alcohols do not react.

Table 2: Reagents and solvents most commonly used in the oxidation of alcohols.
2º Alcohol → ketones and

1º Alcohol → aldehydes

Oxidant [O]Solvent
PCCCH2Cl2

Collins reagent (CrO3 2 pyridine)

Swern reagent ((ClCO)2 / DMSO)

CH2Cl2 or ethers
2º Alcohol → ketones and

1º Alcohol → carboxilic acids

Jones reagent (H2CrO4)

acetone / H2SO4
KMnO4 in a basic mediumH2O with a solvent mixture

Oxidation of 1,2-diols

The neighboring diols can be subjected to an oxidative cleavage process with periodic acid (HIO4) or with lead tetra-acetate to give two carbonyl compounds.

reacciones de alcoholes eteres oxiranos epoxidos oxidacion de 1,2-dioles

Ethers breaking

Ether cleavage with acids of the HX type occurs at room temperature when X = I. For Br it is necessary to increase the temperature to about 100 °C, whereas even higher temperatures are required for Cl.

reacciones de alcoholes eteres oxiranos epoxidos rotura de eteres

Ring-opening of oxiranes

Acid catalyzed

When an oxirane (epoxide, oxacyclopropane) is treated with a mineral acid, protonation of the oxygen atom occurs, which facilitates ring opening by attack of a nucleophile.

reacciones de alcoholes eteres oxiranos epoxidos apertura de oxiranos

In all cases, the attack of the nucleophile is regioselective, since it occurs on the most substituted carbon. The reaction mechanism is of the SN1-process type.

The main reactions are the three indicated in the scheme:

  • Ring opening in aqueous medium to obtain 1,2-glycols.
  • Ring opening in the presence of alcohols to obtain hydroxyethers.
  • Ring opening with hydrogen halides to yield halohydrins.

Nucleophilic

Nucleophiles can open oxiranes by attack on the least substituted carbon atom (regioselective reaction).

reacciones de alcoholes eteres oxiranos epoxidos apertura de oxiranos

In the case of two diastereomeric epoxides, when treated with the same nucleophile under the same reaction conditions, two diastereomers are obtained (diastereospecific reaction). It is a very versatile procedure because a wide variety of different nucleophiles can be used.

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