ALCOHOL PREPARATION METHODS

Hydrolysis of Alkyl Halides

This is a nucleophilic  substitution reaction.

 R-X + KOHaq → R-OH

The method is not satisfactory as olefins are also formed as by-products. However better yields is obtained by using moist Ag2O or aqueous K2CO3. Tertiary butyl halides mainly gives alkene due to dehydrohalogenation. 

Hydration of Alkenes

This is electrophilic addition of H2O to alkenes.

  

Mechanism of Hydration of alkenes:

Protonation of alkene to form carbocation by electrophilic



Nucleophilic attack of water on carbocation.



Deprotonation to form an alcohol.



Except ethyl alcohol no other primary alcohol can be obtained by this method, however hydroboration of terminal alkenes give primary alcohols.

Oxymercuration and Demercuration of Alkanes

Alkenes react with mercuric acetate in presence of H2O and tetra hydrofuran to give alkyl mercury compounds.


Examples:



Hydroboration Oxidation



                                              

From Grignard Reagents

All the three types of monohydric alcohols (primary, secondary and tertiary alcohols) are obtained by the use of Grignard reagents and carbonyl compounds. The addition of RMgX on carbonyl compounds followed with hydrolysis yields alcohols.

   



The Grignard reagent : an organometallic compound

When a solution of an alkyl halide in dry ethyl ether, (C2H5)O, is allowed to stand over turnings of metallic magnesium a vigorous reaction takes place: the solution turns cloudy, begins to boil, and the magnesium metal gradually disappears. The resulting solution is known as a Grignard reagent, after Victor Grignard (of the University of Lyons) who received the Nobel prize in 1912 for its discovery. It is one of the most useful and versatile reagents known to the organic chemist.

CH3I + Mg   CH3MgI

H3CH2Br + Mg   CH3CH2MgBr

Ethyl bromide                Ethylmagnesium bromide

The Grignard reagent has the general formula R MgX, and the general name alkylmagnesium halide. The carbon-magnesium bond is covalent but highly polar, with carbon pulling electrons from electropositive magnesium; the magnesium halogen bond is essentially ionic. R-Mg+X

Since magnesium becomes bonded to the same carbon that previously held halogen, the alkyl group remains intact during the preparation of the reagent. Thus n-propyl chloride yields n­-propylmagnesium chloride, and isopropyl chloride yields isopropylmagnesium chloride.

CH3CH2CH2Cl + Mg    CH3CH2CH2MgCl

 n-Propyl chloride                     n-Propylmagnesium chloride

CH3CHClCH3 + Mg     CH3CHMgClCH3

 Isopropyl chloride               Isopropylmagnesium chloride

The Grignard reagent is the best-known member of a broad class of substances, called organometallic compounds, in which carbon is bonded to a metal: lithium potassium, sodium, zinc, mercury, lead, thallium-almost any metal known. Each kind of organometallic compound has, of course, its own set of properties, and its particular uses depend on these. But whatever the metal, it is less elctronegative than carbon, and the carbon-metal bond-like one in the Grignard reagent - is highly polar. Although the organic group is not a full-fledged carbanion–an anion in which carbon carries negative charge–it nevertheless has considerable carbanion character. As we shall see, organometallic compounds owe their enormous usefulness chiefly to one common quality: they can serve as a source from which carbon is readily transferred with its electrons.

The Grignard reagent is highly reactive. It reacts with numerous inorganic compounds including water, carbon dioxide, and oxygen, and with most kinds of organic compounds; in many of these cases the reaction provides the best way to make a particular class of organic compounds.

The reaction with water to form an alkane is typical of the behaviour of the Grignard reagent–and many of the more reactive organometallic compounds–toward acids. In view of the marked carbanion character of the alkyl group, we may consider the Grignard reagent to be the magnesium salt, R MgX, of the extremely weak acid,

R–H. The reaction 

R MgX + HOH   → R–H   +  Mg(OH)X

            Stronger       Weaker

                acid            acid

is simply the displacement of the weaker acid, R–H, from its salt by the stronger acid, HOH.

R MgX + NH3  →  R–H + Mg(NH2)X

           Stronger    Weaker

             acid        acid

An alkane is such a weak acid that it is displaced from the Grignard reagent by compounds that we might ordinarily consider to be very weak acids themselves, or possibly not acids at all. Any compound containing hydrogen attached to oxygen or nitrogen is tremendously more acidic than an alkane, and therefore can decompose the Grignard reagent: for example, ammonia or methyl alcohol.

RMgX + CH3OH  →  R–H + Mg(OCH3)X

            Stronger       Weaker

             acid            acid

Grignard Synthesis of Alcohols

The Grignard reagent, we recall, has the formula RMgX, and is prepared by the reaction of metallic magnesium with the appropriate organic halide. This halide can be alkyl (1o, 2o, 3o), allylic, aryl alkyl (e.g., benzyl), or aryl (phenyl) or substituted phenyl. The halogen may be –Cl, –Br or –I, (Arylmagnesium chlorides must be made in the cyclic ether tetrahydrofuran instead of ethyl ether.)

Aldehydes and ketones resemble each other closely in most of their reactions. Like the carbon-carbon double bond, the carbonyl group is unsaturated, and like the carbon-carbon bond, it undergoes addition. One of its typical reactions is addition of the Grignard reagent.

Since the electrons of the carbonyl double bond hold together atoms of quite different electronegativity, we would not expect the electrons to be equally shared; in particular, the mobile p cloud should be pulled strongly towards the more electronegative atom, oxygen. Whatever the mechanism involved, addition of an unsymmetrical reagent is oriented so that the nucleophilic (basic) portion attaches itself to carbon, and the electrophilic (acidic) portion attaches itself to oxygen.

The carbon-magnesium bond of the Grignard reagent is a highly polar bond, carbon being negative relative to electropositive magnesium. It is not surprising, then, that in the addition to carbonyl compounds, the organic group becomes attached to carbon and magnesium to oxygen. The product is the magnesium



salt of the weakly acidic alcohol and is easily converted into the alcohol itself  by the addition of the stronger acid, water. Since the Mg(OH)X thus formed is a gelatinous material difficult to handle, dilute mineral acid (HCl, H2SO4) is commonly used instead of water, so that water-soluble magnesium salts are formed.

Products of the Grignard Synthesis

The class of alcohol that is obtained from a Grignard synthesis depends upon the type of carbonyl compoud used: formaldehyde, HCHO, yields primary alcohols; other aldehydes, RCHO, yield secondary alcohols; and ketones, R2CO, yield tertiary alcohols.

This relationship arises directly from our definitions of aldehydes and ketones, and our definitions of primary, secondary, and tertiary alcohols. The number of hydrogens attached to the carbonyl carbon defines the carbonyl compound as formaldehyde, higher aldehyde or ketone. The carbonyl carbon is the one that finally bears the –OH group in the product; here the number of hydrogen defines the alcohol as primary, secondary, or tertiary.

For example:



A related synthesis utilized ethylene oxide to make primary alcohols containing two more carbons than the Grignard reagent. 



Here, too, the organic group becomes attached to carbon and magnesium to oxygen, this time with the breaking of a carbon-oxygen s bond in the highly strained three-membered ring. For example:



Reduction of Carbonyl Compounds

Aldehydes can be reduced to primary alcohols, and ketones to secondary alcohols, either by catalytic hydrogenation or by use of chemical reducing agents like lithium aluminum hydride, LiAlH4. Such reduction is useful for the preparation of certain alcohols that are less available than the corresponding carbonyl compounds, in particular carbonyl compounds that can be obtained by the aldol condensation. For example



Reduction of ketones gives secondary alcohol.

Note : tertiary alcohols can be obtained by this method. 

Sodium borohydride, NaBH4, does not reduce carbon-carbon double bonds, not even those conjugated with carbonyl groups, and in thus useful for the reduction of such unsaturated carbonyl compounds to unsaturated alcohols.Let us look a little more closely at reduction by metal hydrides. Alcohols are formed from carbonyl compounds, smoothly and in high yield, by the action of such compounds as lithium aluminum hydride, LiAlH4. Here again, we see



Nucleophilic addition : this time the nucleophile is hydrogen transferred with a pair of electrons-as a hydride ion, H:-  –from the metal to carbonyl carbon:



Reduction of acids to alcohols: Lithium aluminum hydride, LiAlH4, is one of the few reagents that can reduce an acid to an alcohol; the inital product is an alkoxide from which the alcohol is liberated by hydrolysis:

4RCOOH + 3LiAlH4 → 4RCH2OH              1oalcohol

Because of the excellent yields it gives, LiAlH4 is widely used in the laboratory for the reduction of not only acids but many other classes of compounds. As an alternative to direct reduction, acids are often converted into alcohols by a two-step process: esterification, and reduction of the ester.

Reduction of esters: Like many organic compounds, esters can be reduced in two ways: (A) by catalytic hydrogenation using molecular hydrogen, or (B) chemical reduction. In either case, the ester is cleaved to yield (in addition to the alcohol or phenol from which it was derived) a primary alcohol corresponding to the acid portion of the ester.

RCOOR'    RCH2OH + R'OH

Ester                       1o alcohol

Hydrogenolysis (cleavage by hydrogen) of an ester requires more severe conditions than simple hydrogenation of (addition of hydrogen to) a carbon-carbon double bond. High pressures and elevated temperatures are required: the catalyst used most often is a mixture of oxides known as copper chromite, of approximately the composition CuO.CuCr2O4. For example:

CH3(CH2)10COOCH3    CH3(CH2)10CH2OH + CH3OH

(Methyl dodecanoate)                                (1-Dodecanol)

Chemical reduction is carried out by use of sodium metal and alcohol, or more usually by use of lithium aluminium hydride

By the reduction of acids and their derivatives :

RCOOH                    RCH2OH

(RCO2)O                       RCH2OH

RCOCI                               RCH2OH

RCOOR'                        RCH2OH + R'OH

Note : If C2H5OH + Na is used as reducing agent, the reduction is known as Bouveault-Blane reaction.

By the action of nitrous acid on primary amines :

R-NH2 + HNO2 → R-OH + N2 + H2O

However under similar conditions CH3NH2 gives CH3-O-N=O or CH3OCH3

CH3NH2 + 2HNO2 → CH3-O-N=O + 2H2O + N2

or  2CH3NH2 + 2HNO2 → CH3OCH3 + 2N2 + 3H2O 

Preparation of Methanol: Methanol can also be prepared as

  

Hydroxylation of Alkenes