Alcohols

The organic compounds containing one or more than one hydroxyl group(s) attached to sp3 hybridised carbon atom(s) are called alcohol. Alcohols are bent molecules. In alcohols, the carbon atom linked with ‘O’ atom of –OH group is sp3 hybridised. The central ‘O’ atom is also sp3 hybridised and the bond angle is 105°.

Compounds in which the hydroxyl group is attached directly to a sp2 hybridised carbon atom are known as enols or phenols (in case of aromatic compounds).

For example,

Classification

Alcohols are classified as mono, di and trihydric alcohols accordingly as they contain one, two or three hydroxyl groups. Alcohols which contains four or more hydroxyl groups attached to the sp3 hybridised carbon atoms are called polyhydric alcohols.

Again we can classify monohydric alcohols according to the kind of carbon that bears the –OH group. For example,

Nomenclature

For certain alcohols, common names are used extensively with respect to their IUPAC names. The common names are derived by adding the suffix alcohol to the name of alkyl group. Common names of few alcohols are as follows.

The IUPAC naming rules of alcohols are as follows:

(a) Select as the parent structure, the longest continuous carbon chain that contains the –OH group, then consider the compound to have been derived from this structure by replacement of hydrogen by various groups.

The parent structure is known as ethanol, propanol, butanol, etc., depending upon the number of carbon atoms. Each name is derived by replacing the terminal –e of the corresponding alkane name by –ol.

(b) Indicate by a number, the position of the –OH group in the parent chain, generally using the lowest possible number for this purpose.

(c) Indicate by numbers, the positions of other groups attached to the parent chain.

Alcohols containing two hydroxyl groups are called diols or glycols. They have both common names and IUPAC names. Common names are given in parenthesis.

Illustration 1:

Give the systematic (IUPAC) name for the following alcohol.

Solution:

The longest chain contains six carbon atoms, but it does not contain the carbon bonded to the hydroxyl group. The longest chain containing the carbon bonded to the –OH group is the one indicated by the box, containing 5 carbon atoms.

The chain is numbered from right to left so as to give the hydroxyl bearing carbon atom the lowest possible number.

The correct name for the compound is 3-iodomethyl-2-isopropyl-1-pentanol

Methods of Preparation

Alcohols are prepared by the following methods:

(1) Hydrolysis of Alkyl Halides:

Alkyl halides react with aqueous sodium hydroxide to form alcohols.

(2) Hydration of Alkenes: Alkenes react with sulphuric acid to produce alkyl hydrogen sulphates (Markovnikov rule is followed). Alkyl hydrogen sulphates on hydrolysis give alcohols. For example,

The overall result of the above reactions appears to be Markovnikov addition of H2O (Hydration) to a double bond.

It is not possible to make primary alcohols by this method (ethyl alcohol is the only exception).

(3) Hydroboration-Oxidation of Alkenes: Alkenes react with diborane, B2H6 to form trialkylboranes. Diborane adds as borane, BH3. The positive part of BH3 is the boron, the negative part is hydrogen. For example,

Tri alkylboranes are used for making primary alcohols by reaction with alkaline aqueous solution of hydrogen peroxide.

The overall result of the above reactions appears to be anti-Markovnikov addition of H2O to a double bond.

Hydroxylation

Synthesis of 1, 2 diols from alkene:

Example

Organometallic Reagents

Organometallic compounds contain covalent bonds between carbon atom and metals. Organometallic reagents are useful because they have nucleophilic carbon atoms, in contrast to the electrophilic carbon atoms of alkyl halides. Most metals (M) are more electropositive than carbon and the C–M bond is polarized with a partial +ve charge on the metal and partial negative charge on the carbon atom:

Grignard Reagents

Organometallic compounds of lithium and magnesium are most frequently used for synthesis of alcohols. The organometallic halides of empirical formula R – Mg – X, are called Grignard reagents in honour of the French Chemist Victor Grignard, who discovered this utility around 1905 and received the Nobel Prize in chemistry in 1912. Grignard reagents result from the reaction of an alkyl halide with magnesium metal.

This reaction is always carried out in an ether solvent, which is needed to solvate and stabilize the Grignard reagent as it forms. Although we write the Grignard reagents as R – Mg – X, the actual species in solution usually contains two, three, or four of these units associated together with several molecules of the ether solvent. Diethyl ether, CH3CH2–O–CH2CH3, is the most common solvent for these reactions although other ethers are also used:

$\overset{δ +}{R} - \overset{δ -}{X} + M g \overset{C H_{3} C H_{2} - O - C H_{2} C H_{3}}{\to} \overset{δ -}{R} - \overset{δ +}{M g} - X$

organometallic halide (Grignard reagent)

(X = Cl, Br or I)

Grignard reagents may be made from primary, secondary and tertiary alkyl halides as well as from vinyl and aryl halides. Alkyl iodides are the most reactive halides followed by bromides and chlorides. Alkyl fluorides generally do not react.

Reactivity R – I > R – Br > R – Cl >> R – F

The following reactions show the formation of some typical Grignard reagents

$C H_{3} - I + M g \overset{e t h e r}{\to} C H_{3} - M g - I$

Organolithium Reagents

Like magnesium, lithium reacts with alkyl halides, vinyl halides, and aryl halides to form organometallic compounds. Ether is not necessary for this reaction; organo lithium reagents are made and used in a wide variety of solvents.

$R - X + 2 L i \overset{}{\to} L i^{+} X^{-} + R - L$

Organo lithium reacts like R–: Li+

Example

$C H_{3} C H_{2} C H_{2} C H_{2} - B r + 2 L i \overset{h e x a n e}{\to} C H_{3} C H_{2} C H_{2} C H_{2} + L i + L i B r$

n-butyl bromide n butyl lithium

$C H_{2} = C H - C l + 2 L i \overset{p e n \tan e}{\to} C H L_{2} = C H - L i + L i C$

vinyl chloride

Preparation of alcohols by Grignard’s reagents: addition of organometallic reagents to carbonyl compounds

Because the Grignard reagents resemble carbanions, Grignard and organolithium reagents are strong nucleophiles as well as strong bases. Their most useful nucleophilic reactions are addition to carbonyl ( >C=O) groups. The carbonyl group is polarized, with a partial +ve charge on carbon atom and a partial negative charge on oxygen. The positively charged carbon is electrophile; attack by a nucleophile places a negative charge on oxygen atom.

The product of this nucleophilic attack is an alkoxide ion, a strong base. The addition of water or a dilute acid protonates the alkoxide ion to give the alcohol.

Either a Grignard reagent or an organo metallic reagent can serve as the nucleophile in the addition to carboxyl group. The following discussions refer to Grignard reagents, but they also apply to organometallic reagents.

(i) Preparation of Primary Alcohols

(ii) Preparation of Secondary Alcohols

(iii) Preparation of Tertiary Alcohols

Addition of the first equivalent of the Grignard reagent produces an unstable intermediate that expels a chloride ion (in the acid chloride) or an alkoxide ion (in the ester), giving a ketone. The alkoxide ion is a suitable leaving group in this reaction because on leaving stabilizes a negatively charged intermediate in a strongly exothermic step.

Attack on an acid chloride

Attack on an ester

The ketone, thus produced reacts with a second equivalent of the Grignard reagent, forming the magnesium salt of a tertiary alkoxide. Protonation gives a tertiary alcohol with one of its alkyl groups derived from the acid chloride or ester, and the other two derived from the Grignard reagent.

(iv) Addition of Grignard Reagents to Ethylene Oxide

Grignard reagents usually do not react with ethers, but epoxides are usually reactive ethers because of their ring strain. Ethylene oxide reacts with Grignard’s reagents to give after protonation, primary alcohols with two additional carbon atoms.

The nucleophilic attack by Grignard reagents opens the ring and relieves the ring strain.

Reaction with Acidic compounds

Grignard and organolithium reagents react vigorously and irreversibly with water. Therefore, all reagents and solvents used in these reactions must be dry.

For example, consider the reaction of ethyl lithium with water.

The products are strongly favoured in the reaction. Ethane is a very weak acid (Ka of about 10–50). So the reverse reaction (abstraction of a proton from ethane by lithium hydroxide) is unlikely. When ethyl lithium is added to water ethane is instantly bubbled to the surface.

Why would we want to add an organometallic reagent to water? This is method for reducing an alkyl halide to an alkane.

The overall reaction is a reduction because it replaces the electronegative halogen atom with hydrogen atom. In particular, this reaction provides a way to “label” a compound with deuterium at any position where a halogen to present.

The Grignard reagent is a very powerful base as it contains a carbanion. Thus, it is not possible to prepare a Grignard reagent from an organic compound that contains an acidic hydrogen atom.

For example, prepare Grignard reagent from a compound containing an –OH group, an –NH – group, an –SH group, a –COOH group, or an –SO3H group. If we were to attempt to prepare a Grignard reagent from an organic alkyl halide containing any of these groups, the formation of the Grignard reagent would simply fail to take place because the Grignard reagent that would be produced on the 1st step, it would immediately react with an acidic group.

Since Grignard reagents are powerful nucleophiles, we cannot prepare a Grignard reagent from any organic halide that contains a carbonyl, epoxy, nitro or cyano (–CN) group. Compounds containing the following groups can not be used to prepare the Grignard reagent, –OH, –NH2, –NHR, –COOH, –SO3H, –SH, –C ≡ C – H,

Planning a Grignard Synthesis

By using Grignard synthesis skilfully one can synthesize almost any alcohol. In planning a Grignard synthesis we must simply choose the correct Grignard reagent and the correct aldehyde, ketone, ester or epoxide. We do this by examining the alcohol we wish to prepare and by special attention to the groups attached to the carbon atom bearing the –OH group. Many time there may be more than one way of carrying out the synthesis. In these cases our final choice will probably be dictated by the availability of starting compounds. Let us consider the following example.

Suppose we want to prepare the following compound.

This means we can synthesize this compound in several different ways.

(i) We can use a ketone with isopropyl group and methyl group (3-methyl 2 butanon) and allow to react with phenyl magnesium bromide.

(ii) We can use a ketone containing an propyl group and a phenyl group (propyl phenyl ketone) and allow it to react with methyl magnesium bromide

(iii) We can use an ester of benzoic acid and allow it to react with one equivalent of methyl magnesium bromide and one equivalent propyl magnesium bromide

Illustration 2:

Using an alcohol of no more than four carbon atoms as your only starting material, outline a synthesis of A:

Solution:

Synthesis

Illustration 3:

Starting with bromobenzene and any other needed reagents, outline a synthesis of the following ketone.

Solution:

Reaction of Grignard reagent to α, β unsaturated aldehydes and ketones

When Grignard reagents (RMgX) react $α - β$ unsaturated aldehydes and ketones, they do so in two ways. They may react by a simple addition that is one in which the nucleophile adds across the double bond of the carbonyl groups; or they may react by a conjugate addition. These two processes resemble the 1, 2 and the 1, 4 addition reaction of conjugated dienes.

When organolithium compounds made to undergo the afore-said reaction with conjugated aldehyde or ketone, they yield 1, 2 addition product in much higher percentage (almost exclusively) as compared with the Grignard reagents.

Alcohols by Reduction of Carbonyl Compounds

Primary and Secondary alcohols can be synthesized by reduction of variety of compounds that contain the carbonyl group several examples are shown here,

The two most useful hydride reagents, sodium borohydride (NaBH4) and Lithium aluminium hydride (LiAlH4) reduce carboxyl groups in excellent yields. These reagents are called complex hydrides because they do not have a simple hydride structure such as Na+ H– or Li+ H–. Instead, their hydrogen atoms, bearing partial negative charges, are covalently bonded to boron and aluminum atoms. This arrangement makes the hydride a better nucleophile while reducing its basicity.

Of these reducing agents, lithium aluminium hydride (LAH) is much stronger and more difficult to work with LAH as reacts explosively with water and alcohols, liberating hydrogen gas and sometimes initiates fires. Sodium boronhydride reacts slowly with alcohols and with water as long as the pH is high (basic). Sodium borohydride is a convenient and highly selective reducing agent.

(i) Uses of Sodium Borohydride

Sodium borohydride (NaBH4) reduces aldehydes to primary alcohols, and ketones to secondary alcohols. The reactions take place in a wide variety of solvent including alcohols, ethers, and water. The yields are generally excellent.

Sodium borohydride is selective; it usually does not react with carbonyl groups that are less reactive than ketones and aldehydes. For example, carboxylic acids and esters are unreactive towards borohydric reaction. Sodium borohydride can reduce a ketone or an aldehyde in the presence of an acid or ester.

(ii) Uses of Lithium Aluminium Hydride

Lithium aluminium hydride (LiAlH4, abbreviated as LAH) is a much stronger reagent than sodium borohydride. It easily reduces ketones and aldehydes and also the less reactive carboxyl groups e.g. those in acids, esters, and other acid derivatives.

LAH reduces ketones to secondary alcohols and aldehydes, acids and esters to primary alcohols.

LAH reduces both keto and ester group in a compound like;

Catalytic hydrogenation of ketones and aldehydes.

The conversion of acetone or an aldehyde to an alcohol involves adding two hydrogen atoms across the C = O group. This addition can be accomplished by catalytic hydrogenation commonly using Raney Nickel as the catalyst. If any unsaturation (double bond) present in addition to aldehyde or ketone will get reduced by this reagent.

From Amines

When 1° aliphatic amines are treated with nitrous acid, the –NH2 group gets converted into –OH group and alcohols are formed. Nitrous acid is very unstable and usually it is prepared by treating aqueous and dilute sodium nitrite solution with dilute acids, HCl, H2SO4, acetic acid etc.

$R - N H_{2} + H N O_{2} \overset{}{\to} R - O H + N_{2} ↑ + H_{2} O$

However, carbonium ions being the intermediates of the reaction, several side products and rearranged products are obtained as shown below.

Thus, in this reaction, isomeric alcohols are obtained through the nucleophilic attack by water on the carbonium ions; they may undergo the nucleophilic attack by the X– to form inorganic esters. Isomeric alkenes also form through the E1 reaction of the carbonium ions; alkenes and esters are the side products of the reaction. Besides these, a small amount of cycloalkene is also obtained.

Illustration 4:

Identify A, B and C

Solution:

Illustration 5:

Solution:

Addition EtMgBr will only be governed by the steric effects.

If the Et attack at 1-carbon atom, this will experience a smaller steric effects. Therefore product (1) will be major product.

Illustration 6:

Convert CHD2I into CHD2CH2OH. What alkenes would you expect to get by the acid catalyzed dehydration of the alcohol? Explain.

Solution:

Since deuterium shows a kinetic isotope effect therefore removal of deuterium occur more slowly. Thus (A) will be the major product and (B) will be the minor product.

Alcohol Ether Phenol

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