9.

Reactions of Alcohols Because the electronegativity of oxygen is greater than that of carbon and hydrogen, the oxygen atom polarizes the electrons of both the CO and the OH bonds of alcohols. The oxygen atom is a nucleophilic center while the neighboring carbon and hydrogen are weak electrophilic centers.

Most of alcohols reactions involve the heterolytic cleavage of O-H bond, C-O bond, or both. 9.1. Reactions involving O-H cleavage 9.1.1. Acidity of alcohols Due to the presence of electrophilic hydrogen, alcohols can act as very weak acids. They are weaker acids than water. The alcohol alkyl groups are electronreleasing group and increase the electron density on oxygen tending to decrease the polarity of O-H bond. Only a strong base such sodamide (NaNH2) or sodium hydride (NaH) can deprotonate an alcohol to yield an alkoxide ion (RO). Metallic sodium (Na) or potassium (K) is often used to form an alkoxide by reducing the proton to hydrogen gas. The nucleophilicity of the oxygen in alcohols are enhanced by conversion to its conjugate base (an alkoxide). Alkoxides can be useful reagents as nucleophiles and bases.

The acidic strength of alcohols decreases while going from primary to secondary to tertiary alcohols because the +I effect of the alkyl groups not only inhibits the polarity of the O-H group but also destabilize the ions of the conjugate bases of acids (alkoxides).The acidic strength of compounds decreases in the following order:

-The relative stability of conjugate bases of acids OH- > CH3-O- > R-CH2-O- > R2-CH-O- > R3-C-O- > R-C=C9.1.2. Alcohols as nucleophile Due to the presence of the nucleophilic oxygen, alcohols can act both as weak bases and weak nucleophiles. 9.1.2.1. Formation of alkyl ester Alcohols react with inorganic acids, carboxylic acids in the presence of inorganic catalyst, acyl chlorides (acid chlorides) or acid anhydrides to give alkyl esters. 9.1.2.1.1. Formation of inorganic esters. Alcohols react with inorganic acids such as nitric acid , sulfuric acid or phosphoric acid to form inorganic esters (Alkyl nitrate , alkyl sulfate or alkyl phosphate respectively) .For examples:

The best known nitrate ester is nitroglycerine ( glyceryl trinitarte ) which results from the reaction of glycerol (1,2,3-propanetriol) with three molecules of nitric acid . Although Nitroglycerine is a highly explosive substance, it is used in treatment of angina pectoris.

9.1.2.1.2. Formation of organic esters 9.1.2.1.2.1. Reactions of alcohols with carboxylic acids: Fischer esterification reactions Alcohols react with carboxylic acids (R-COOH) in the presence of acid catalyst usually H2SO4 or HCl gas to form esters .The reaction is a reversible process and is known as Fischer esterification reaction. For example.

The acid catalyst protonates the carbonyl oxygen to enhance the electrophilicity of carbonyl carbon.The reaction mechanism involves nucleophilic substitution of the carboxylic acid hydroxyl group as water molecule by the alkoxy group of the alcohol.

9.1.2.1.2.2. Reaction of alcohols with acid halides or acid anhydride Alcohol such as ethanol reacts with acid halides such as benzoyl chloride or acid anhydrides such as acetic anhydride to form esters. This reaction is irreversible process. For example :

The reaction mechanism involves nucleophilic substitution of the chloride ion from the acid chloride or the carboxylate ion from the anhydride by the alkoxy group of the alcohol.The reaction goes through nucleophilic addition of the alkoxy group of the alcohol at the electrophilic carbonyl carbon of the acid halide or anhydride followed by elimination of the leaving group ( chloride ion or carboxylate ion) , and formation of the ester.

9.1.2.1.2.3. Reactions of alcohols with sulfonyl chlorides: Synthesis of mesylates and tosylates Alcohols reacts with sulfonyl chlorides to give alkyl sulfonate esters. Two common examples of alkyl sulfonates are mesylates and tosylates. They are prepared from the reaction of alcohols with methanesulfonyl chloride (mesyl chloride) and ptoluenesulfonyl chloride (tosyl chloride) respectively in the presence of organic base such as pyridine or triethylamine.

The reaction mechanism involves nucleophilic substitution of the chloride ion of the sulfonyl chloride by the alkoxy group of the alcohol. The base serves to mop up the HCl which is formed to avoid the revirsability of the reaction.

Mesylates and tosylates groups convert the hydroxyl group of an alcohol from a poor leaving group into a very good leaving group. Therefore, the alkyl mesylate or alkyl tosylates, like alkyl halides, undergo readily nucleophilic substitution reaction, in which wide variety of nucleophiles replace the mesylate or tosylate groups. They form less basic and stable anions in which the negative charge is delocalized over three electronegative oxygen atoms.

9.1.2.3. Formation of ethers: Williamson ether synthesis Unlike alcohol itself, 1o, 2o or 3o alkoxide acts as a strong nucleophile and reacts with 1o alkyl halide (R-CH2-X) to form dialkyl ether (R-O-R1). The reaction involves SN2 process. This reaction is called Williamson ether synthesis. When the alkyl halide is not primary, alkoxides act as bases and elimination (dehydrohalogenation) reaction takes place to give alkene.

9.2. Reactions involving C-O bond cleavage Although the carbon atom bearing the OH group of the alcohols is electrophilic, direct nucleophilic substitution of the hydroxyl group does not occur because the strongly basic hydroxide ion is a poor leaving group. However, An alcohols CO bond can be split if the hydroxyl group is converted into a better leaving group. 9.2.1. Conversion of alcohols into alkyl halides. Alcohols are converted to alkyl halides using a number of methods. All methods involve the conversion of the OH group into a better leaving groups by using one of the following reagents: Hydrohalic acids (HX), phosphorus trihalides (PCl3 or PBr3) or thionyl chloride (SOCl2). 9.2.1.1. Reaction of alcohols with hydrohalic acids (HX) Alcohols react with hydrogen halides to give alkyl halides and water.

In acidic medium, protonation of the oxygen of the hydroxyl group converts the hydroxyl group into less basic better leaving group (water molecule) which is displaced with the halide ion through nucleophilic substitution reaction.
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-While 1o alcohols react with HX by SN2 reaction, 3o alcohols react by SN1, the reaction of 2o alcohols with HX proceed via either SN2 or SN1 mechanisms. SN2 reaction mechanism

SN1 reaction mechanism

The order of reactivity of hydrohalic acids (HX) in this reaction is: HI > HBr > HCl. Chloride ion is a weaker nucleophile than bromide ion because it is smaller and less polarizable. An additional Lewis acid such as zinc chloride ( ZnCl2) is necessary to promote the reaction of HCl with 1o and 2o alcohols. Zinc chloride coordinates with the oxygen of alcohol in the same way a proton does, except that zinc chloride coordinate more strongly.

9.2.1.2. Lucas test: Distinction between 1o, 2o and 3o alcohols Alcohols forms insoluble alkyl chloride with Lucas reagent (a mixture of concentrated HCl and zinc chloride). The difference in the rate of reaction of the three classes of alcohols (1o, 2o, and 3 ) with Lucas reagent at room temperature is used for identification of the class of the alcohol. - 3o alcohols react immediately with Lucas reagent and form white turbidity 3 o alkyl chloride at once. - 2o alcohols react with Lucas reagent in about five minutes and form white turbidity of 2o alkyl chloride. - 1o alcohols dont react at room temperature with Lucas reagent and the solution remains clear.
o

9.2.1.3. Reaction of alcohols with phosphorus trihalide The OH group of alcohols is converted into a neutral better leaving group (HOPX2) by an initial SN2 reaction of alcohol at phosphorus of PX3. Then, the produced halide ion replaces the neutral leaving group (HOPX2) the alcohol molecule either via SN1 in case of tertiary alcohols or SN2 in case of 1o alcohols.

9.2.1.4. Reaction of alcohols with thionyl chloride (SOCl2) Alcohols react with thionyl chloride (SOCl2) in the presence of a nitrogen base (e.g. triethylamine or pyridine) to give alkyl chlorides. The OH group of alcohols is converted into a neutral better leaving group (OSOCl) by nucleophilic attack of ROH on the sulfur atom of thionyl chloride. An intermediate alkyl chlorosulfite (ROSOCl) is formed. Then, the produced chloride ion displaces the OSOCl (leaving group) either via SN1 or SN2 mechanism depending on the alcohol structure. The organic base (triethylamine or pyridine) is used to mob up the HCl formed during the reaction. The reaction is also helped by the fact that one of the products (SO 2) is lost as a gas, thus driving the reaction to completion.

9.3. Acid-catalyzed dehydration of alcohols Heating of 1o, 2o or 3o alcohols in the presence of acid catalyst such as H2SO4 or phosphoric acid (H3PO4) eliminates a molecule of water from adjacent carbon atoms and forms alkenes. Elimination of water from a molecule is called dehydration. Dehydration is favoured at higher temperature. The dehydration of alcohols follows Zaitsev's rule to form the more substituted alkenes as the major products.
OH H2SO4or H3PO4 1800 c Cyclohexanol cyclohexene

OH CH3CH2CHCH3 2-Butanol

85% H3PO4 heat

CH3CH=CHCH3 + CH3CH2CH=CH2 2-Butene ( major) 1-Butene ( minor) ( Comment)

Dehydration of alcohols in acid medium starts by protonation of the oxygen of the hydroxyl group in order to convert the hydroxyl group from a poor leaving group into less basic better leaving group (water molecule). The acid catalysed water elimination from alcohols (3o, 2o or 1o except ethanol) involves 2 step ionic reaction mechanism, termed E1 reaction mechanism. - The first step involves slow ionization and departure of water molecule from the protonated alcohol molecule leaving a carbocation intermediate. It is the rate determining step. - The second step is fast and involves the removal of the carbocation -hydrogen as a proton by a base (the conjugate base of the acid used). The electrons pair from the old C-H is used to form the new pi bond.

Acid catalyzed dehydration of ethanol involves E2 reaction mechanism because of the difficulty of formation a 1o carbocation. E2 reaction is a concerted one step process in which the pi bond is formed simultaneously with the departure of both the -hydrogen and water from the alcohol molecule.

9.4. Oxidation of alcohols: Distinction between 1o, 2o and 3o alcohols. The oxidation of alcohols is an extremely important reaction not only in organic synthesis but also as chemical test to distinguish the three classes (1o, 2o and 3o) of alcohols. While 1o alcohols are oxidized either to aldehydes or carboxylic acids depending on the reagent chosen, 2o alcohols are oxidized to ketones. 3o alcohols are resistant to oxidation. 9.4.1. Oxidation of 1o alcohols Chromic acid (H2CrO4) or basic aqueous potassium permanganate (KMnO4) oxidizes 1o alcohols to carboxylic acids. It is difficult to stop the oxidation at aldehyde state.

Pyridinium chlorochromate (PCC) solution in dichloromethane (CH2Cl2) oxidizes a 1o alcohol to an aldehyde only without further oxidation.

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PCC is prepared by dissolving CrO3 in aqueous HCl and adding pyridine to precipitate PCC as a solid. 9.4.2. Oxidation of 2o alcohols 2o Alcohols are easily oxidized to ketones by using chromic acid , potassium permanganate or PCC . For examples.

9.5. Haloform reactions: Identification test 1o and 2o Alcohols that contain a H3C-CHOH group or any adehyde or ketone that contains -COCH3 undergo haloform reaction with excess halogens (I2, Br2 or Cl2) in the presence of base such as aqueous sodium or potassium hydroxide. The reaction is called haloform reaction and leads to the formation of a trihalomethane and a salt of carboxylic acid.

The haloform reaction using iodine in aqueous sodium hydroxide is called iodofrom test because it is used as a laboratory test to determine the presence of either H3C-CHOH or -COCH3 group in organic molecules. A positive test is indicated by the formation of yellow precipitate of triiodomethane termed iodoform (m.p.119oC). The mechanism of haloform reaction involves three steps - The first step involves oxidation of alcohol molecule to methyl carbonyl compound (-COCH3).

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- The second step involves base-promoted replacement of the hydrogen of the methyl group by halogens in 3 consecutive steps. - The third step involves nucleophilic substitution whereby the hydroxide ion substitutes the trihalomethyl carbanion (-CX3, a good leaving group due to the three electron withdrawing halogen atoms) and formation of trihalomethane with carboxylic acid salt.

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