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Alcohols can behave as weak acids, undergoing deprotonation. The deprotonation reaction to produce an alkoxide salt is either performed with a strong base such as sodium hydride or n-butyllithium, or with sodium or potassium metal.
2 R-OH + 2 NaH ? 2 R-O-Na+ + H2?
2 R-OH + 2Na ? 2R-O-Na + H2
E.g. 2 CH3CH2-OH + 2 Na ? 2 CH3-CH2-O-Na + H2
Water is similar in pKa to many alcohols, so with sodium hydroxide there is an equilibrium set up which usually lies to the left:
R-OH + NaOH <=> R-O-Na+ + H2O (equilibrium to the left)
It should be noted, though, that the bases used to deprotonate alcohols are strong themselves. The bases used and the alkoxides created are both highly moisture sensitive chemical reagents.
The acidity of alcohols is also affected by the overall stability of the alkoxide ion. Electron-withdrawing groups attached to the carbon containing the hydroxyl group will serve to stabilize the alkoxide when formed, thus resulting in greater acidity. On the other hand, the presence of electron-donating group will result in a less stable alkoxide ion formed. This will result in a scenario whereby the unstable alkoxide ion formed will tend to accept a proton to reform the original alcohol.
With alkyl halides alkoxides give rise to ethers in the Williamson ether synthesis.
The OH group is not a good leaving group in nucleophilic substitution reactions, so neutral alcohols do not react in such reactions. However if the oxygen is first protonated to give R-OH2+, the leaving group (water) is much more stable, and nucleophilic substitution can take place. For instance, tertiary alcohols react with hydrochloric acid to produce tertiary alkyl halides, where the hydroxyl group is replaced by a chlorine atom. If primary or secondary alcohols are to be reacted with hydrochloric acid, an activator such as zinc chloride is needed. Alternatively the conversion may be performed directly using thionyl chloride.
Alcohols may likewise be converted to alkyl bromides using hydrobromic acid or phosphorus tribromide, for example:
3 R-OH + PBr3 ? 3 RBr + H3PO3
In the Barton-McCombie deoxygenation an alcohol is deoxygenated to an alkane with tributyltin hydride or a trimethylborane-water complex in a radical substitution reaction.
Alcohols are themselves nucleophilic, so R-OH2+ can react with ROH to produce ethers and water in a dehydration reaction, although this reaction is rarely used except in the manufacture of diethyl ether.
More useful is the E1 elimination reaction of alcohols to produce alkenes. The reaction generally obeys Zaitsev's Rule, which states that the most stable (usually the most substituted) alkene is formed. Tertiary alcohols eliminate easily at just above room temperature, but primary alcohols require a higher temperature.
This is a diagram of acid catalysed dehydration of ethanol to produce ethene.
A more controlled elimination reaction is the Chugaev elimination with carbon disulfide and iodomethane.
To form an ester from an alcohol and a carboxylic acid the reaction, known as Fischer esterification, is usually performed at reflux with a catalyst of concentrated sulfuric acid:
R-OH + R'-COOH ? R'-COOR + H2O
In order to drive the equilibrium to the right and produce a good yield of ester, water is usually removed, either by an excess of H2SO4 or by using a Dean-Stark apparatus. Esters may also be prepared by reaction of the alcohol with an acid chloride in the presence of a base such as pyridine.
Other types of ester are prepared similarly- for example tosyl (tosylate) esters are made by reaction of the alcohol with p-toluenesulfonyl chloride in pyridine.
Primary alcohols (R-CH2-OH) can be oxidized either to aldehydes (R-CHO) or to carboxylic acids (R-CO2H), while the oxidation of secondary alcohols (R1R2CH-OH) normally terminates at the ketone (R1R2C=O) stage. Tertiary alcohols (R1R2R3C-OH) are resistant to oxidation.
The direct oxidation of primary alcohols to carboxylic acids normally proceeds via the corresponding aldehyde, which is transformed via an aldehyde hydrate (R-CH(OH)2) by reaction with water before it can be further oxidized to the carboxylic acid.
Often it is possible to interrupt the oxidation of a primary alcohol at the aldehyde level by performing the reaction in absence of water, so that no aldehyde hydrate can be formed.
Reagents useful for the transformation of primary alcohols to aldehydes are normally also suitable for the oxidation of secondary alcohols to ketones. These include:
* Chromium-based reagents, such as Collins reagent (CrO3·Py2), PDC or PCC.
* Activated DMSO, resulting from reaction of DMSO with electrophiles, such us oxalyl chloride (Swern oxidation), a carbodiimide (Pfitzner-Moffatt oxidation) or the complex SO3·Py (Parikh-Doering oxidation).
* Hypervalent iodine compounds, such as Dess-Martin periodinane or IBX.
* Catalytic TPAP in presence of excess of NMO (Ley oxidation).
* Catalytic TEMPO in presence of excess bleach (NaOCl) (Anelli’s oxidation).
Allylic and benzylic alcohols can be oxidized in presence of other alcohols using certain selective oxidants such as manganese dioxide (MnO2).
Reagents useful for the oxidation of secondary alcohols to ketones, but normally inefficient for oxidation of primary alcohols to aldehydes, include chromium trioxide (CrO3) in a mixture of sulfuric acid and acetone (Jones oxidation) and certain ketones, such as cyclohexanone, in the presence of aluminium isopropoxide (Oppenauer oxidation).
The direct oxidation of primary alcohols to carboxylic acids can be carried out using:
* Potassium permanganate (KMnO4).
* Jones oxidation.
* PDC in DMF.
* Heyns oxidation.
* Ruthenium tetroxide (RuO4).
Alcohols possessing two hydroxy groups located on adjacent carbons —that is, 1,2-diols— suffer oxidative breakage at a carbon-carbon bond with some oxidants such as sodium periodate (NaIO4) or lead tetraacetate (Pb(OAc)4), resulting in generation of two carbonyl groups.
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