CHAPTER 17ALCOHOLS & PHENOLS:

Generalizations:

  • Alcohols and phenols may be thought of as organic derivatives of water (H-O-H). If one H is replaced by an alkyl group (R-), the compound is an alcohol (R-OH) and if the H of water is replaced by an aromatic group (Ar-), the compound is a phenol (Ar-OH). Although alcohols and phenols have the same functional group (a hydroxyl group), their physical properties are very different.

Alcohols:

  • Alcohols are classified as 1, 2, or 3 depending upon the number of carbon atoms bonded to the -carbon, i.e., the carbon bearing the functional group (-OH in this case).

Sec. 17.1Naming Alcohols:

  • Common names are derived by naming the alkyl group attached to the -OH group and then, after leaving a space, name the -OH group as 'alcohol'. They are literally ‘alkyl alcohols’.
  • IUPAC names are derived by replacing the terminal '-e' in the alkane with '-ol' giving an ‘alkanol’, written as a single word.
  1. As with alkenes and alkynes, choose the longest carbon chain containing the
    - carbon atom, i.e., the carbon that bears the hydroxyl (-OH) group.
  1. Number the chain to give -OH the lowest number.
  1. List the substituents on the chain alphabetically.

CH3OHCH3CH2OHCH3CH2CH2OH

cmethyl alcohol (carbinol)ethyl alcoholn-propyl alcohol

Imethanolethanol1-propanol

cisopropyl alcoholn-butyl alcoholsec-butyl alcohol

I2-propanol1-butanol2-butanol

ct-butyl alcoholn-pentyl alcohol------

n-amyl alcohol

I2-methyl-2-propanol1-pentanol2-pentanol

cisopentyl alcohol ------t-pentyl alcohol

isoamyl alcoholt-amyl alcohol

I3-methyl-1-butanol 3-pentanol 2-methyl-2-butanol

cbenzyl alcoholcyclopentyl alcohol ------

Iphenylmethanolcyclopentanol trans-2-bromocyclohexanol

Note that in cyclic alcohols, the -OH group is automatically on carbon # 1.

callyl alcoholethylene glycol glycerol

glycerin

I2-propen-1-ol1,2-ethanediol 1,2,3-propanetriol

c ------neopentyl alcohol ------

I 2-ethylcyclobutanol 2,2-dimethyl-1-propanol 3-phenyl-2-butanol

Nomenclature of Phenols:

Phenols are usually named as derivatives of the parent compound, phenol. Note that phenol is both a specific compound and a class of compounds. In addition, methyl substituted phenols are called cresols while benzene diols have names based on their historical uses rather than their structures.

ccarbolic acid -naphthol-naphthol

Iphenol 1-naphthol2-naphthol

cp-cresolm-cresolo-cresol

I4-methylphenol3-methylphenol2-methylphenol

ccatecholresorcinol hydroquinone

I1,2-benzenediol1,3-benzenediol1,4-benzenediol

Ibiphenyl2-methyl-4-(1-methylethyl)phenol4-bromo-2-methylphenol

4-isopropyl-2-methylphenol

Do problems 17.1 & 17.2
Sec. 17.1Sources and Uses of Simple Alcohols:

  1. Methanol (methyl hydrate, methyl alcohol, wood alcohol, carbinol) was formerly produced by pyrolysis (destructive distillation) of wood. It is commonly used as ‘gas line antifreeze’. Methanol is toxic by ingestion, causing blindness in small amounts (15 mL) and death in larger amounts.

Methanol is produced commercially by catalytic reduction of CO. The catalyst is ZnO/CrO3.

400 ºC

CO + 2 H2  CH3OH

ZnO / CrO3

  1. Ethanol (ethyl alcohol, alcohol, grain alcohol) has been produced for several thousand years by fermentation of grains and sugars. Currently, most (~95%) of the ethanol produced industrially is by acid-catalyzed hydration of ethylene.
  1. Phenol occur widely in nature. Phenol itself is a general disinfectant found in coal tar; methyl salicylate is a flavoring in oil of wintergreen; urushiols are allergens in poison oak and poison ivy.

Boiling Points:

  • Alcohols and phenols have similar geometry to HOH. The R-O-H bond angle is approximately tetrahedral (109) and the ‘O’ atom is sp3 hybridized.
  • Because of the presence of the hydroxyl group, alcohols (and phenols) have significantly higher boiling points than their constitutional (structural) isomers, the ethers. For example, ethyl alcohol and dimethyl ether are constitutional isomers having the same molecular weight (46). The bp of ethanol is 78 C and the bp of dimethyl ether is -24C, a difference of 102 C! The hydroxyl groups of alcohols and phenols form intermolecular hydrogen bonds. The attractive force of hydrogen bonds must be overcome when molecules in the liquid separate into the gaseous state during boiling.
  • The bp of ethers are similar to those of alkanes of equivalent MW. For example, diethyl ether (‘Quick Start’) with MW = 44, has a bp of 35 C and n-pentane (MW = 44) is also 35 C.
  • Similarly, phenols have higher bp’s than aromatic ethers and aromatic hydrocarbons for the same reasons as discussed above. Phenol has a mp of 43 C and toluene has a mp of -95 C.

Do problem 17.3
Solubility:

The hydroxyl group of alcohols is the first functional group we have encountered that has a large effect on water-solubility of the organic compound. In general, alkanes, alkenes, alkynes, arenes and their halogen derivatives (alkyl halides, etc.) are insoluble in water.

The presence of the -OH group makes alcohols with up to 3 carbons miscible (infinitely soluble) in water. As the carbon chain becomes longer, the solubility decreases; as it becomes more branched, the solubility increases somewhat.

Hydrocarbon Solubility in Water

Compound / H2O Solubility (g/100 mL, 25 C)
n-pentane / 0.05
carbon tetrachloride / 0.08
n-butyl bromide / 0.06
1,5-hexadiene / 0.10

Alcohol and Ether Solubility in Water

Compound / H2O Solubility (g/100 mL, 20 C)
n-butyl alcohol / 9
sec-butyl alcohol / 12
isobutyl alcohol / 10
tert-butyl alcohol / miscible
n-pentyl alcohol / 2.7
n-hexyl alcohol / 0.6
1-heptanol / 0.2
phenol / 6.7
1-octanol / 0.05
1,4-butanediol / miscible
3-chloro-1-butanol / insoluble
dimethyl ether / very soluble
diethyl ether / 7
diisopropyl ether / insoluble

Note that the addition of an extra hydroxyl group in diols (vs. alcohols) increases solubility but the halogen atom has the opposite effect.

A compound is considered ‘soluble’ if its solubility exceeds 3 parts of compound per 100 parts of solvent, i.e., 3%.

Ethers of low MW have some solubility in water because the O-atom of an ether carries a partial negative charge and is therefore a H-bond acceptor.

SEC. 17.3 PROPERTIES OF ALCOHOLS/PHENOLS: ACIDITY & BASICITY

Like water, alcohols and phenols are both weakly basic and weakly acidic, i.e., amphiprotic.

  • As bases, they are reversibly protonated by strong acids to yield oxonium ions, ROH2+
  • As acids, they dissociate to a slight extent in dilute aqueous solution by donating a proton to water, generating H3O+ and an alkoxide ion, RO-, or a phenoxide ion, ArO-.

The acidity constants of some alcohols are listed and compared with water ...

Alcohol / pKa
(CH3)3COH / 18.00
CH3CH2OH / 16.00
HOH / 15.74
CH3OH / 15.54
CF3CH2OH / 12.43
(CF3)3COH / 5.4
p-aminophenol / 10.5
phenol / 9.9
p-nitrophenol / 7.2
2,4,6-trinitrophenol / 0.60
  • Simple alcohols, like methanol and ethanol have acidity similar to water.
  • t-butyl alcohol is less acidic because its alkoxide anion is bulky and not easily solvated by water
  • 2,2,2-trifluoroethanol is more acidic than ethanol because the highly electronegative F-atoms inductively withdraw electron density from the alkoxide anion thus stabilizing the anion
  • nonafluoro-tert-butyl alcohol is quite acidic because of its 9 highly electronegative F-atoms.

Because alcohols are only weakly acidic, they don't react with weak bases such as bicarbonates, ammonia, or amines and they only react to a very slight extent with metal hydroxides, e.g., NaOH. Prove this to yourself by calculating (pKeq) for several alcohols and these bases.

Alcohols, like H2O, do react with alkali and alkaline earth metals (Na, Mg, etc.) and with very strong organic bases such as sodium hydride (NaH), sodium amide (NaNH2), alkyllithium reagents (RLi) such as methyl lithium (:CH3-Li+) and Grignard reagents (RMgX) such as methyl magnesium bromide (:CH3- +MgBr). Metal alkoxides themselves are strong bases that are frequently used in organic chemistry.

Phenols are ca. 106 times more acidic than alcohols. They are soluble in dilute aq. NaOH soln. The phenoxide anion is resonance stabilized (negative charge is delocalized over the o- and p-positions. Electron donating groups reduce the acidity of phenols but withdrawing groups increase phenolic

Do problems 17.4 and 17.5.

Sec. 17.4, 17.5 & 17.6Preparation of Alcohols:

Alcohols can be prepared from many compounds and are likewise used to prepare many compounds...

Methods of Preparation of Alcohols:

  1. Hydrolysis of Alkyl Halides: OH-, a strong base and a good nucleophile, can displace a halide from methyl and 1º alkyl halides (a nucleophilic substitution reaction) producing alcohols. The reaction does not apply to 2º and 3º alkyl halides because strong bases cause them to eliminate HX (an elimination reaction) forming alkenes.

Reflux means boiling the system without boiling anything over, i.e., recondensing above the distillation flask with a condenser.

  1. Hydration of Alkenes:

Acid catalyzed hydration follows Markovnikov’s rule and is subject to rearrangement via hydride or methide shifts, e.g., 1º C+  2º C+  3º C+.
Recall that Markovnikov alcohols can be produced by hydration of alkenes without rearrangement via oxymercuration-demercuration (1. Hg(OAc)2 in THF (aq.), 2. NaBH4)

Also recall that anti Markovnikov alcohols are produced from alkenes by hydroboration-oxidation (1. BH3 in THF, 2. H2O2, pH 8)

Do problem 17.6 a) & b)

  1. Reduction of Aldehydes and Ketones:

Sodium borohydride (NaBH4) is a safe, effective reducing agent for this reaction.
Aldehydes are reduced to 1 alcohols. Ketones are reduced to 2 alcohols. Carbon-to-carbon double bonds in both these compounds are not reduced.
Lithium aluminum hydride (LiAlH4) can also be used, giving higher yields, but it is explosive in water and when heated.

Mechanism:

The carbonyl carbon is electrophilic (+). Hydride is a strong base (pKb = -21) and is the most powerful of nucleophiles. As hydride bonds with the carbonyl carbon, the C-to-O  bond (the weakest bond) breaks (carbon can never have 5 bonds). The electronegative oxygen atom readily accepts the negative charge. In a second step, dilute aqueous acid is added. The hydronium ion protonates the alkoxide producing an alcohol and destroys any excess hydride reagent at the same time.


Note that hydrides do not reduce (saturate) alkenes since alkenes are also nucleophilic.

  1. Reduction of Carboxylic Acids and Esters:

These reactions require a stronger reductant than NaBH4, which reduces esters very slowly and does not reduce carboxylic acids. LiAlH4 is effective here, reducing both esters and carboxylic acids to 1 alcohols.

Note that 2 H's are added to a carboxylic acid from LiAlH4 and 1 H from H3O+.
Note that a total of 4 H's are added when esters are reduced and two 1º alcohols are formed.

Hydride is a strong base and so will first abstract an acidic hydrogen (proton) from the carboxylic acid. Hydride is such a strong nucleophile that it can attack even the negatively charged carboxylate anion (the carbonyl carbon in the carboxylate is only weakly electrophilic). The –- OAlH3 is a very poor leaving group (very reactive) and only leaves because H- is even more reactive. Note that aldehydes, esters and carboxylic acids all reduce to 1º alcohols with hydride. Only ketones are reduced to 2º alcohols.

Do problems 17.7 & 17.8.

  1. Reduction of Carbonyls with Grignard Reagents:

Grignards, RMgX, reduce carbonyl compounds to alcohols similar to LiAlH4

Grignard reagents: When Mg metal is added to alkyl halides, aryl halides, or vinylic halides in a solvent such as ether or tetrahydrofuran (THF), Mg is inserted between the -carbon and the halide; the carbon becomes strongly electronegative (and nucleophilic).

CH3-Br + Mg  CH3-MgBror in general ….

R-X + Mg  R-MgXwhere R = 1º, 2, or 3 alkyl, aryl, or vinylic

where X = Cl, Br, or I

Grignards are useful reducing agents. They react with formaldehyde, CH2=O, to give
1 alcohols. They react with higher aldehydes to give 2 alcohols, and with ketones and esters to give 3 alcohols.

Write a complete mechanism for Grignard reduction of an ester.

Carboxylic acids don’t give alcohols with Grignards because their acidic hydrogen reacts with the strongly basic Grignard to yield a hydrocarbon and a Mg-salt of the acid. A Grignard is not as strong a nucleophile as LiAlH4 and the carboxylate anion is not attacked by a Grignard as it is with the very powerful hydride nucleophile. Actually Grignards are sometimes used for precisely the purpose of converting an alkyl halide to an alkane via a Grignard reaction.

Grignards also add to other compounds that have an electropositive atom, i.e.,

Limitations of the Grignard Reaction: Grignards cannot be prepared when reactive groups are present along with the halide, e.g., acidic H’s in carboxylic acids.

  • Grignards are destroyed (protonated) by even weakly acidic functional groups All of the groups listed in the table below have a terminal H that is acidic enough to react with the strongly basic Grignard.

ArCOOH /

RCOOH

/ ArSH / RSH / ArOH / R-OH / amide / -CC-H / ArNH2 / RNH2
pKa / 4 / 5 / 7 / 10 / 10 / 16 / 17 / 25 / ~30 / 35

Assuming alkyl amines (pKa ~ 35) to be the weakest acid that would react with a Grignard, calculate the approximate pKb of a Grignard.

Do problems 17.9, 17.10 & 17.11

Sec.17.7Reactions of Alcohols:

Alcohols, like water, are amphoteric, i.e., they can act as both acids and bases. The pKa and pKb of simple alcohols are both in the range of 16-19. In alcohols, both the -C and the hydroxyl-H are + while the hydroxyl-O is  -. The lone pairs of electrons on the hydroxyl-O make it basic and nucleophilic. The + H makes it weakly acidic.

a)Strong bases can abstract the weakly acidic H from alcohols producing alkoxides

b)In the presence of strong acids, alcohols act as bases and accept protons. This is the same as what occurs when strong acids are dissolved in water, i.e., the hydroxyl-O accepts a proton from the acid and H3O+ forms.

c)Good nucleophiles, like HS-, CN-, I-, and Br-, may attack and bond with the -carbon causing the C-O bond to break, resulting in a substitution. The hydroxyl group, however, is a poor leaving group in substitution reactions for several reasons. First, the C-OH bond is very strong (>90 kcal/mol) and is difficult to break. Second, the hydroxyl group must leave as OH- and charge separation always requires high energy input. Substitution of the OH group is much easier if the hydroxyl group is first protonated as in reaction b) above. The leaving group is then a neutral molecule, i.e., H2O.

  1. Dehydration of Alcohols to Alkenes:

3 alcohols are dehydrated by warm (50 C) aqueous H2SO4 in THF. Elimination follows Zaitsev’s rule, producing the more highly substituted alkene.

2 and 1 alcohols require severe conditions (conc. H2SO4 & heat!). Recall the dehydration of cyclohexanol to cyclohexene. Under these conditions, product may be charred or rearrange (if more highly substituted carbocations can form).


A safer approach, to dehydrating 1º and 2º alcohols is to react them with phosphorus oxychloride (POCl3) in pyridine (C5H5N) - a basic amine solvent. The reaction will proceed even at 0 C. Pyridine (pKb = 5.3) is a basic solvent. The mechanism is E2 (no C+ forms and no rearrangements occur) .

This also works with 3 alcohols (E2) but the reagent is nasty and should be avoided if possible.

Do problem 17.12

  1. Conversion of Alcohols into Alkyl Halides (Sec. 17.7):

This is another C-O bond breaking reaction of alcohols. HI, HBr, or HCl react readily with
3 alcohols, moderately with 2 alcohols, and poorly with 1 alcohols. For example, t-butyl alcohol reacts rapidly with conc. HCl at 25 C forming t-butyl chloride. 1 and 2 alcohols are unreactive under these conditions but 2º alcohols will react if ZnCl2 catalyst is added.

  • These differences provide the basis of a qualitative test (Lucas test) to distinguish alcohols. Lucas reagent = ZnCl2 dissolved in conc. HCl. Formation of an alkyl chloride from an alcohol is indicated by the cloudiness that appears when the alkyl chloride separates from the aqueous solution. 3º, allyl and benzyl alcohols react in seconds (even without ZnCl2). 2º alcohols react in 1 to 5 minutes (only with ZnCl2). 1º alcohols require from 10 minutes to days to react unless heated. Note that alcohols must be soluble in Lucas reagent otherwise any alkyl halide produced will not appear as cloudiness but will simply dissolve in the organic (alcoholic) layer. Alcohols of not more than 6 carbons are soluble in the Lucas reagent.
  • As in the dehydration reaction studied in the last section, 1 and 2 alcohol reactivity can be improved by reacting with a reagent which makes the -OH group a better leaving group. Phosphorus tribromide (PBr3) and thionyl chloride (SOCl2) react quickly by SN2 mechanism. Whereas reaction with HX is reversible, these reactions proceed to completion.
  • 3 alcohols will also react quickly with PBr3 and SOCl2 but via an SN1 mechanism. Since SOCl2 and PBr3 are corrosive, we would normally choose a mineral acid (HCl, HBr or HI) to produce an alkyl halide from a 3º alcohol.


  1. Reaction of Alcohols as Acids: (a qualitative lab test for alcohols)

Active metals such as Na, Li, K, Ca, etc. are strong bases (as well as strong reducing agents) and will deprotonate alcohols. Alcohols act as acids in this case and form alkoxide salts.





Write an equation for the reaction of cyclohexanol and lithium. Name the product.

Elimination Often Competes with Substitution:

  • Strong dehydrating acids (H2SO4, H3PO4) favor elimination (dehydration) in alcohols. Because they are strong acids, they readily protonate the alcohol thereby converting a poor leaving group (OH-) into a better leaving group (HOH), however, the anions produced after protonation of the alcohol (HSO4- or H2PO4-) are very poor nucleophiles and can’t replace the leaving group, so elimination (dehydration) occurs.

CH3CH2-OH + H2SO4 (catalyst)  CH2=CH2 + H2O(elimination)

(CH3)2CH-OH + H2SO4 (catalyst) CH3CH=CH2 + H2O(elimination)

(CH3)3C-OH + H2SO4 (catalyst) (CH3)2C=CH2 + H2O(elimination)

  • Strong non-dehydrating acids (like HI, HBr and HCl) also readily protonate an alcohol creating a better leaving group (HOH) but with the difference that the resulting Nu:-’s (like I, Br-, and Cl), are better Nu:-’s and readily replace the leaving group which results in substitution instead of elimination.

CH3CH2-OH + HBr  CH3CH2-Br + H2O(substitution)

(CH3)2CH-OH + HBr  (CH3)2CH-Br + H2O(substitution)

(CH3)3C-OH + HBr  (CH3)3C-Br + H2O (substitution)

  1. Oxidation of Alcohols (Sec. 17.8):

This represents the opposite of reduction of carbonyls to alcohols.

  • 1 alcohols have 2 -hydrogens and can either lose one of them to yield aldehydes or lose both of them to form carboxylic acids (depending on the oxidant strength)
  • 2 alcohols can lose their only -hydrogen to yield ketones or under severe oxidation conditions, can be cleaved to carboxylic acids.
  • 3 alcohols don’t have any -hydrogens and so don’t normally oxidize except under severe oxidation conditions in which case they can dehydrate to alkenes which are subsequently oxidized and cleaved to carboxylic acids.
  • Oxidants include acidic or basic aq. KMnO4, Na2Cr2O7 in HAc, NaOCl in aq. HAc, CrO3 in aq. H2SO4 + acetone (Jones reagent), CrO3 in pyridine (Collins reagent), or PCC, i.e., pyridinium chlorochromate, (C5H5NCrO3Cl) in dichloromethane solvent.

a)1 alcohols are oxidized only to aldehydes by the anhydrous oxidants (Collins reagent or PCC) which are mild. The aqueous oxidants will oxidize 1 alcohols to carboxylic acids.

b)2 alcohols yield ketones using any of the above oxidants except the strongest (hot KMnO4, hot H2CrO4, or hot conc. HNO3) which dehydrate them to alkenes and subsequently cleave the alkenes to carbonyl compounds (See Ch. 7 on alkene cleavage)