Alcohol

In chemistry, alcohol (from Arabic al-kukhūl &#1575;&#1604;&#1603;&#1581;&#1608;&#1604; = "the spirit", "the chemical") is any organic compound in which a hydroxyl group (-OH) is bound to a carbon atom, which in turn is bound to other hydrogen and/or carbon atoms. The general formula for a simple acyclic alcohol is CnH2n+1OH.

In general usage, alcohol refers almost always to ethanol, also known as grain alcohol, and often to any beverage that contains ethanol (see alcoholic beverage). This sense underlies the term alcoholism (addiction to alcohol). As a drug, ethanol is known to have a depressing effect that decreases the responses of the central nervous system (see effects of alcohol on the body). Other forms of alcohol are usually described with a clarifying adjective, as in isopropyl alcohol or by the suffix -ol, as in isopropanol.

Structure


The functional group of an alcohol is a hydroxyl group bonded to an sp³ hybridized carbon. It can therefore be regarded as a derivative of water, with an alkyl group replacing one of the hydrogens. If an aryl group is present rather than an alkyl, the compound is generally called a phenol rather than an alcohol. Also, if the hydroxyl group is bonded to one of the sp² hybridized carbons of an alkenyl group, the compound is referred to as an enol. The oxygen in an alcohol has a bond angle of around 109&deg; (c.f. 104.5&deg; in water), and two nonbonded electron pairs. The O-H bond in methanol (CH3OH) is around 96 picometres long.

Primary, secondary, and tertiary alcohols
There are three major subsets of alcohols- 'primary' (1°), 'secondary' (2°) and 'tertiary' (3°), based upon the number of carbons the C-OH carbon (shown in red) is bonded to. Methanol is the simplest 'primary' alcohol. The simplest secondary alcohol is isopropanol (propan-2-ol), and a simple tertiary alcohol is tert-butanol (2-methylpropan-2-ol).



Methanol & ethanol
The simplest and most commonly used alcohols are methanol and ethanol (common names methyl alcohol and ethyl alcohol, respectively), which have the structures shown above.

Methanol was formerly obtained by the distillation of wood, and was called "wood alcohol". It is now a cheap commodity chemical produced by the high pressure reaction of carbon monoxide with hydrogen. In common usage, "alcohol" often refers simply to ethanol or "grain alcohol". Methylated spirits ("Meths"), also called "surgical spirits", is a form of ethanol rendered undrinkable by the addition of methanol. Aside from its major use in alcoholic beverages, ethanol is also used (though highly controlled) as an industrial solvent and raw material.

Uses
Alcohols are in wide use in industry and science as reagents, solvents, and fuels. Ethanol and methanol can be made to burn more cleanly than gasoline or diesel. Because of its low toxicity and ability to dissolve non-polar substances, ethanol is often used as a solvent in medical drugs, perfumes, and vegetable essences such as vanilla. In organic synthesis, alcohols frequently serve as versatile intermediates.

Ethanol is also commonly used in beverages after fermentation to promote flavor or induce a euphoric intoxication commonly known as "drunkenness" or "being drunk". The use of ethanol for this purpose is illegal in some jurisdictions. In such instances of consumption, alcohol is a drug, with immediate potential for overdose, toxic poisoning, and physiological dependency (known as alcoholism). Alcoholism has become one of the most common drug addictions (if not second to caffeine) in the world. The physiological dependency caused by alcoholism means that the user experiences physical withdrawal (in the form of a headache known as a "hangover," extremely high anxiety known as "the shakes," and restlessness or trouble sleeping) upon cessation or decrease of use. For the full article on this topic see effects of alcohol on the body.

Systematic names
In the IUPAC system, the name of the alkane chain loses the terminal "e" and adds "ol", e.g. "methanol" and "ethanol". When necessary, the position of the hydroxyl group is indicated by a number between the alkane name and the "ol": propan-1-ol for CH3CH2CH2OH, propan-2-ol for CH3CH(OH)CH3. Sometimes, the position number is written before the IUPAC name: 1-propanol and 2-propanol. If a higher priority group is present (such as an aldehyde, ketone or carboxylic acid), then it is necessary to use the prefix "hydroxy", for example: 1-hydroxy-2-propanone (CH3COCH2OH).

Some examples of simple alcohols and how to name them:



Common names for alcohols usually take the name of the corresponding alkyl group and add the word "alcohol", e.g. methyl alcohol, ethyl alcohol or tert-butyl alcohol. Propyl alcohol may be n-propyl alcohol or isopropyl alcohol depending on whether the hydroxyl group is bonded to the 1st or 2nd carbon on the propane chain. Isopropyl alcohol is also occasionally called sec-propyl alcohol.

As mentioned above alcohols are classified as primary (1°), secondary (2°) or tertiary (3°), and common names often indicate this in the alkyl group prefix. For example (CH3)3COH is a tertiary alcohol is commonly known as tert-butyl alcohol. This would be named 2-methylpropan-2-ol under IUPAC rules, indicating a propane chain with methyl and hydroxyl groups both attached to the middle (#2) carbon.

An alcohol with two hydroxyl groups is commonly called a "glycol", e.g. HO-CH2-CH2-OH is ethylene glycol. The IUPAC name is ethane-1,2-diol, "diol" indicating two hydroxyl groups, and 1,2 indicating their bonding positions. Geminal glycols (with the two hydroxyls on the same carbon atom), such as ethane-1,1-diol, are generally unstable. For three or four groups, "triol" and "tetraol" are used.

Etymology
The word "alcohol" almost certainly comes from the Arabic language (the "al-" prefix being the Arabic definite article); however, the precise origin is unclear. It was introduced into Europe, together with the art of distillation and the substance itself, around the 12th century by various European authors who translated and popularized the discoveries of Islamic alchemists.

A popular theory, found in many dictionaries, is that it comes from &#1575;&#1604;&#1603;&#1581;&#1604; = ALKHL = al-kuhul, originally the name of very finely powdered antimony sulfide Sb2S3 used as an antiseptic and eyeliner. The powder is prepared by sublimation of the natural mineral stibnite in a closed vessel. According to this theory, the meaning of alkuhul would have been first extended to distilled substances in general, and then narrowed to ethanol. This conjectured etymology has been circulating in England since 1672 at least (OED).

However, this derivation is suspicious since the current Arabic name for alcohol, &#1575;&#1604;&#1603;&#1581;&#1608;&#1604; = ALKHWL = al???, does not derive from al-kuhul. The Qur'an in verse 37:47 uses the word &#1575;&#1604;&#1594;&#1608;&#1604; = ALGhWL = al-ghawl &mdash; properly meaning "spirit" ("spiritual being") or "demon" &mdash; with the sense "the thing that gives the wine its headiness". The word al-ghawl also originated the English word "ghoul", and the name of the star Algol. This derivation would, of course, be consistent with the use of "spirit" or "spirit of wine" as synonymous of "alcohol" in most Western languages. (Incidentally, the etymology "alcohol" = "the devil" was used in the 1930s by the U.S. Temperance Movement for propaganda purposes.)

According to the second theory, the popular etymology and the spelling "alcohol" would not be due to generalization of the meaning of ALKHL, but rather to Western alchemists and authors confusing the two words ALKHL and ALGhWL, which have indeed been transliterated in many different and overlapping ways.

Physical and chemical properties
The hydroxyl group generally makes the alcohol molecule polar. Those groups can form hydrogen bonds to one another and to other compounds. Two opposing solubility trends in alcohols are: the tendency of the polar OH to promote solubility in water, and of the carbon chain to resist it. Thus, methanol, ethanol, and propanol are miscible in water because the hydroxyl group wins out over the short carbon chain. Butanol, with a four-carbon chain, is moderately soluble because of a balance between the two trends. Alcohols of five or more carbons (Pentanol and higher) are effectively insoluble because of the hydrocarbon chain's dominance.

Because of hydrogen bonding, alcohols tend to have higher boiling points than comparable hydrocarbons and ethers. All simple alcohols are miscible in organic solvents. This hydrogen bonding means that alcohols can be used as protic solvents.

The lone pairs of electrons on the oxygen of the hydroxyl group also makes alcohols nucleophiles.

Alcohols, like water, can show either acidic or basic properties at the O-H group. With a pKa of around 16-19 they are generally slightly weaker acids than water, but they are still able to react with strong bases such as sodium hydride or reactive metals such as sodium. The salts that result are called alkoxides, with the general formula RO- M+.

Alcohols conjugated to aromatic rings have a lower pKa (around 10). Electron-withdrawing groups also work to make alcohols more acidic. For example, Para-nitro phenol has a pKa of 7.15.

Meanwhile the oxygen atom has lone pairs of nonbonded electrons that render it weakly basic in the presence of strong acids such as sulfuric acid. For example, with methanol:



Alcohols can also undergo oxidation to give aldehydes, ketones or carboxylic acids, or they can be dehydrated to alkenes. They can react to form ester compounds, and they can (if activated first) undergo nucleophilic substitution reactions. For more details see the section below.

Toxicity
Alcohols often have an odor described as 'biting' that 'hangs' in the nasal passages. Ethanol in the form of alcoholic beverages has been consumed by humans since pre-historic times, for a variety of hygienic, dietary, medicinal, religious, and recreational reasons. While infrequent consumption of ethanol in small quantities may be harmless or even beneficial, larger doses result in a state known as drunkenness or intoxication and, depending on the dose and regularity of use, can cause acute respiratory failure or death and with chronic use has medical repercussions.

Other alcohols are substantially more poisonous than ethanol, partly because they take much longer to be metabolized, and often their metabolism produces even more toxic substances. Methanol, or wood alcohol, for instance, is oxidized by alcohol dehydrogenase enzymes in the liver to the poisonous formaldehyde, which can cause blindness or death.

An effective treatment to prevent formaldehyde toxicity after methanol ingestion is to administer ethanol. This will bind to alcohol dehydrogenase, preventing methanol from binding and thus acting as a substrate. Any formaldehyde will be converted to formic acid and excreted before it causes damage.

Laboratory
Several methods exist for the preparation of alcohols in the laboratory.
 * Primary Alkyl halides react with aqueous NaOH or KOH mainly to primary alcohols in nucleophilic aliphatic substitution. (Secondary and especially tertiary alkyl halides will give the elimination (alkene) product instead).
 * Aldehydes or ketones are reduced with sodium borohydride or lithium aluminium hydride. (after an acidic workup)
 * Alkenes engage in a acid catalysed hydration reaction using concentrated sulfuric acid as a catalyst which gives usually secondary or tertiary alcohols.
 * The hydroboration-oxidation and oxymercuration-reduction of alkenes are more reliable in organic synthesis.
 * Grignard reagents react with carbonyl groups to secondary and tertiary alcohols

The formation of a secondary alcohol via reduction and hydratation is shown:



Industrial
Industrially alcohols are produced in several ways.
 * by fermentation using glucose produced from sugar from the hydrolysis of starch, in the presence of yeast and temperature of less than 37°C to produce ethanol. For instance the conversion of invertase to glucose and fructose or the conversion of glucose to zymase and ethanol.
 * By direct hydration: using ethene or other alkenes from cracking of fractions of distilled crude oil. Uses a catalyst of phosphoric acid under high temperature and pressure.
 * Methanol is producted from water gas: It is manufactured from synthesis gas, where carbon monoxide and 2 equivalents of hydrogen gas are combined to produce methanol using a copper, zinc oxide and aluminium oxide catalyst at 250°C and a pressure of 50-100 atm.

Deprotonation
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 &rarr;  2 R-O-Na+  +  H2&uarr;


 * 2 R-OH + 2Na &rarr; 2R-O&minus;Na+


 * e.g. 2 CH3CH2-OH + 2 Na &rarr;  2 CH3-CH2-O&minus;Na+

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.

Nucleophilic substitution
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&minus;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.[1]



Alcohols may likewise be converted to alkyl bromides using hydrobromic acid or phosphorus tribromide, for example:


 * 3 R-OH +  PBr3  &rarr;  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.

Dehydration
Alcohols are themselves nucleophilic, so R&minus;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 requre a higher temperature.

This is a diagram of acid catalysed dehydration of ethanol to produce ethene:



Esterification
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  $$\Leftrightarrow$$  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.

Oxidation
Primary alcohols generally give aldehydes or carboxylic acids upon oxidation, while secondary alcohols give ketones. Traditionally strong oxidants such as the dichromate ion or potassium permanganate are used, under acidic conditions, for example:


 * 3 CH3-CH(-OH)-CH3 +  K2Cr2O7  +  4 H2SO4  &rarr;  3 CH3-C(=O)-CH3  +  Cr2(SO4)3  +  K2SO4  +  7 H2O

Frequently in aldehyde preparations these reagents cause a problem of over-oxidation to the carboxylic acid. To avoid this, other reagents such as PCC, Dess-Martin periodinane, 2-Iodoxybenzoic acid, TPAP or methods such as Swern oxidation are now preferred.

Alcohols with a methyl group attached to the alcohol carbon can also undergo a haloform reaction (such as the iodoform reaction) in the presence of the halogen and a base such as sodium hydroxide.

Tertiary alcohols resist oxidation, but can be oxidised by reagents such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.