Alcohols, Phenols, Ethers, Epoxides, Thiols, &Sulfides

I.    Alcohols & Phenols
The functional group present in an alcohol or phenol is the hydroxyl group (-OH).    An alcohol can be understood as an alkylated water, that is a carbon chain (R-) is substituted for a hydrogen atom on water.    A phenol substitutes an aromatic ring (Ar-) for one hydrogen atom on water.
Water Alcohol Methanol Ethanol Phenol
H-OH R-OH CH3-OH CH3-CH2-OH Ar-OH

Naming Alcohols and Phenols
Alcohols are classified depending upon the number of organic groups (R-) bonded to the hydroxyl bearing carbon.
Type of Alcohol No. of R- groups General Formula Example
Primary (1o) 1 CH3CH2-OH
Ethanol
Secondary (2o) 2
2-Propanol
Tertiary (3o) 3
2-Methyl-2-butanol

IUPAC rules for naming alcohols
1.  Identify the longest continuous chain of carbons in which the hydroxyl group is attached to one of the carbons in the chain.
2.  Number the chain so that the hydroxyl group is attached to the lowest numbered carbons. (i.e., the OH has priority even over halo groups.)
3.  Identify and locate the other branches on the chain so that they are named alphabetically and their carbon number is hyphenated onto the front of the name. If more than one of the same group is present use the Greek prefix attached to the branch name. (2 = di, 3 = tri, etc.)
4.  After all the branches have been named and located then attach the carbon number that is attached to the hydroxyl group onto the alkane name associated with the number of carbons found in the continuous chain in step 1.
5.  Drop the "e" on the alkane, alkene, or alkyne name and attach the characteristic IUPAC ending "ol" to the rest of the alkane, alkene, or alkyne name.
6.  For polyhydroxy alcohols, locate two or more carbons bearing the hydroxyl groups and hyphenate those carbon numbers to the front of the alkane name and attach "diol" if two are involved, "triol" if three hydroxyl groups are involved, etc.
7.  If an alkene and an alkyne also contains the -OH group, the name is expressed as:
    (alkene)     ___-en ___ol   [first blank gives position of double bond, second blank the position of -OH group]
    (alkyne)     ___-yn ___ol  [first blank gives position of triple bond, second blank the position of -OH group]
 
methanol   CH3-OH 2-propanol 
2-methyl-1-butanol  2-methyl-2-butanol 
2-phenylethanol  cyclohexanol 
2-propen-1-ol  3-butyn-2-ol 

The common names for alcohols are derived from the alkyl group corresponding to the parent compound.
Isopropyl alcohol = 2-Propanol
Ethyl alcohol = Ethanol
CH3CH2OH
Ethylene glycol = 1,2-Ethanediol

Nomenclature of Phenols
If the hydroxyl group of a phenol is the principal group, it is given the number 1, and the compound is named as a substituted phenol. Phenols containing one substituent other than the OH group can be named by either ortho, meta, para system or by number.  Phenols containing more than one substituent are named by number.

Carboxyl and acyl groups have priority over the phenolic hydroxyl group.

Properties of Alcohols and Phenols
An alcohol molecule can be compared to a water molecule.   In an alcohol molecule, the hydroxyl oxygen and the two atoms bonded to it are all in the same plane and have a bond angle of approximately 104o.   The bond angle in alcohols is approximately the tetrahedral value of 109o.   The oxygen is sp3 hybridized.  The oxygyen-hydrogen bond of an alcohol is the same as the oxygen-hydrogen bond length of water.

The hydroxyl group is polar.    There is a partial negative charge (d-) on the oxygen atom and a partial positive charge (d+) on the hydrogen of the hydroxyl group.

The ability of the hydroxyl group to hydrogen bond explains the higher boiling point of the alcohol when compared to its alkane parent or the analogous chloroalkane.  The intermolecular attraction is higher in the alcohol so that the temperature must be raised to boil the substance.   Other factors being equal, hydrogen-bonded molecules have higher boiling points than molecules that are not.

Recall that a hydrogen bond is an intermolecular attraction in which a hydrogen atom bonded to a small electronegative atom (normally N, O, or F) is attracted to an unshared electron pair on another small electronegative atom.
 

Lone pairs on N, O, and F.


Hydrogen bonding between water molecules.

Hydrogen bonding between alcohol molecules.

Hydrogen bonding network in methanol.

Solubility Rule of Thumb:  An organic compound is generally miscible with water if the carbon to oxygen ratio in the compound does not exceed 4:1.  Methanol, CH3OH, is completely miscible, while 1-decanol, CH3(CH2)8CH2OH, is immiscible.

Acidity and Basicity of Alcohols and Phenols
Alcohols are amphoteric (amphiprotic) that is they can act as a weak base or as a weak acid.  Alcohols accept protons from stong acids to yield an oxonium ion, ROH2+.   Alcohols undergo a slight dissociation in dilute aqueous solution by donating  a proton to water to yield an alkoxide ion, RO-.

Simple alcohols are about as acidic as water.  The pKa values of most alcohols are of the order of  18 (Ka = 10-18).  Water has a pKa value of about 16 (Ka = 10-16).  Recall that as pKa values decrease (Ka values increase) the acidity increases.  Substituent groups can have a significant effect.
 
Relative Acidity
MeOH > H2O > ROH > RC=CH > H2 > NH3 > RH
Except for methanol, most alcohols are slightly less acidic than water.

Alcohols are much weaker acids than carboxylic acids or mineral acids and do not react with weak bases (e.g., amines or bicarbonate ion , and react only slightly with strong bases (e.g., NaOH).

Water reacts with alkali metals to produce alkali metal hydroxide and hydrogen.
2 H-OH + 2 Na ----> 2 NaOH + H2

Alcohols react with alkali metals to produce alkali metal alkoxide and hydrogen.
2 R-OH + 2 Na ----> 2 NaOR + H2

Alcohols also react with strong bases such as sodium hydride (NaH), sodium amide (NaNH2), and Grignard reagents (RMgX).
R-OH + NaH ----> Na1+ OR1- + H2
R-OH + RMgX ----> R-H + RO-MgX

Alkoxides are strong bases and are oftern used as reagents in organic synthesis.

The most characteristic property of phenols is their acidity.  Phenols are weak acids but are about a million times more acidic than alcohols.  For example, phenol has a pKa value of about 10 (Ka = 1 x 10-10 ) and ethanol has a pKa value of about 16 (Ka = 1 x 10-16 ).  Due to there acidity, phenols are soluble in dilute aqueous NaOH.

The phenoxide ion is stabilized by delocalization of the negative charge on the oxygen to the ring.


Alkyl substitution of phenols produces  negligible changes in acidity.  Only when the substituent is an electron-withdrawing groups (i.e., nitor groups) is a substantial change in acidity noted.

Synthesis of Alcohols
A.  Synthesis of alcohols from alkenes:

A1.   Acid catalyzed hydration of alkenes
     (Reversible, rearrangement products, Markovnikov, limited to industrial prod.)
                                    (Markovnikov's rule = "Them that has, get's!")

A2.   Hydroboration of alkenes (syn stereochemistry, non-Markovnikov)

A3.  Oxymercuration of alkenes ( regioselective - Markovnikov)

A4.  Hydroxylation of alkenes to yield 1,2-diols (syn stereochemistry)

A5.  Hydroxylation of alkenes to yield 1,2-diols (anti stereochemistry)

B.  Synthesis of alcohols from reduction of carbonyl compounds
B1.  Reduction of aldehydes and ketones
Aldehydes are reduced to 1o alcohols and ketones to 2o alcohols.

[H] = Sodium borohydride: (1) NaBH4/ethanol (2) H3O+  or  Lithium aluminum hydride: (1) LiAlH4/ether (2) H3O+
 Lithium aluminum hydride >>> reactive than Sodium borohydride

B2.  Reduction of carboxylic acids and esters
    Sodium borohydride reacts very slowly with esters and not at all with acids.
    Lithium aluminum hydride: (1) LiAlH4/ether (2) H3O+, is the reagent of choice.
    Carboxylic acids and esters are reduced to give primary alcohols.

C.  Synthesis of alcohols from carbonyl compounds reacting with Grignard reagents
    Formaldehyde + Grignard ----- > 1o alcohols

    Aldehydes + Grignard ----- > 2o alcohols

    Ketones + Grignard ----- > 3o alcohols

Esters  + 2 Grignard ---->  3o alcohol (two R substituents come from the Grignard reagent)

Carboxylic acids dont give addition products.  Grignards cannot be prepared from molecules containing -OH, -HN, -SH, -COOH functional groups.
    RCO2H + R'-MgX ------> R-CO21- 1+MgX + R'H

Reactions of Alcohols
A.    Alcohols react with alkali metals, sodium hydride (NaH), or sodium amide (NaNH2) to produce alkoxide ions.

Phenols react with sodium hydroxide to give the phenoxide ion.

Alkoxides and phenoxides are strong bases and are used as reagents.

B.    Dehydration of alcohols to yield alkenes
B1.     3o alcohol + H3O1+ ---> Alkene
     Order of dehydration reactivity: 3o > 2o > 1o

    Zaitsevs rule is followed and the more substituted alkene is preferred product.  (The poor get poorer.)

B2.    Phosphorus oxychloride (POCl3) in the basic amine solvent pyridine is less harsh and can effect
          dehydration  of secondary and tertiary at 0oC.

C.  Conversion alcohols into alkyl halides
C1.    Tertiary alcohol + HCl or HBr at 0oC ------> alkyl halide
           R-OH + HX---> R-X
    Reactivity of ROH: allyl, benzyl > 3o > 2o > 1o        Reactivity of HX: HI > HBr > HCl

C2.    Primary and secondary alcohols are best converted using SOCl2 or PBr3.

D.    Conversion of alcohols into tosylates and mesylates

Tosylates and mesylates are good leaving groups.
Nu:1- + RCH2-OTos ----> RCH2-Nu + -OTs1-

E.    Oxidation of Alcohols
In organic terminology:
        Oxidation [O] is:
                1. The addition of oxygen to a molecule.
                2. The removal of hydrogen from a molecule.
        Reduction [H] is:
                1. The removal of oxygen from a molecule.
                2. The addition of hydrogen to a molecule.
 
Oxidation of a primary alcohol yields an aldehyde or carboxylic acid.
[O]
1o alcohol ------> Aldehyde

[O] 
1o alcohol ------> Carboxylic acid

Oxidation of a secondary alcohol yields an ketone.
[O]
2o alcohol ------> Ketone
Tertiary alcohols do not undergo oxidation.
          [O]
3o alcohol ------> NR
[O] = KMnO4, CrO3, Na2Cr2O7   (These oxidize primary alcohols to carboxylic acids.)

Milder oxidation is accomplished by using pyridinium chlorochromate (PCC, C5H6NCrO3) in dichloromethane (CH2Cl2).

Secondary alcohols are oxidized to ketones using in Na2Cr2O7 in acetic acid.

Synthesis of Phenols
Phenols are rings with an -OH group directly bonded to an aromatic ring, ArOH.
Phenol is the name of both a specific compound and of a class of compounds.

A.  Alkali fusion of aromatic sulfonates (limited to alkyl-substituted phenols)
                            (1) SO3/H2SO4
        Toluene   ----------------------->  p-Methylphenol
                            (2) NaOH/300oC
                            (3) H3O1+

B.    Hydrolysis of arenediazonium salts
                                                  (1) HNO2/H2SO4
    2-Bromo-4-methylaniline  ---------------------------> 2-Bromo-4-methylphenol
                                                 (2)  H3O1+

Reactions of Phenols
A1.     Electrophilic Aromatic Substitution Rxns of Phenols
            The -OH group is a strongly activating, ortho- and para-directing substituent in EAS reactions.

B.    Oxidation of Phenols: Quinones
Treatment of a phenol with any of a number of oxidizing agents yields 2,5-cyclohexadiene-1,4-dione (benzoquinone).

 phenol + Fremy's salt [(KSO3)2NO] ---> Benzoquinone

Spectroscopy of Alcohols and Phenols
IR
O-H stretching absorption at 330-3600 cm-1

NMR
Carbon atoms bonded to electron-withdrawing OH groups are deshielded and absorb at a lower field in the C-13 NMR spectrum.   Most C-OH absorptions fall in the range of 50-80 d.

Hydroxyl hydrogens are also deshielded and occur in the range of 3.5-4.5 d.

D2O exchange will cause the OH absorption to disappear.



II.    Ethers, Epoxides, Thiols, Sulfides

An ether can be seen as a water molecule with both hydrogens substituted by some R group (e.g. R = alkyl or aryl).
H-O-H    R-O-R
Water     Ether
Ethers are generally unreactive and often used as solvents.

Thiols R-SH (sulfur analogs of alcohols)

Sulfides R-S-R  (sulfur analogs of ethers)

Ether Nomenclature
Two systems:
1.  Simple ethers with no other functional groups are named by identifying the two organic substituents and adding the word ether.
a.  symmetrical ethers have both groups identical.
    Methyl ether or dimethyl ether = CH3-O-CH3
    Phenyl ether = Ph-O-Ph
b.  unsymmetrical ethers have different groups
    Ethyl methyl ether = CH3-O-CH2-CH3
    Phenyl propyl ether = Ph-O-CH2-CH2-CH3
2.  If other functional groups are present or if one group has no simple name, the compound may be named as a alkoxy derivative (an alkoxy, RO-, is named as a substituent). These groups are never treated as principal groups. The principal chain is the longest continuous chain or, in case of chains of equal length, the most highly branched chain.
    1-Ethoxyhexane = CH3CH2-O-CH2CH2CH2CH2CH2CH3

Structure, Properties, and Sources of Ethers
Bond angle in alcohol is approximately tetrahedral value of (112o in dimethyl ether).    The oxygen is sp3 hybridized.     Ethers are slightly polar.

Synthesis of Ethers
A.  The Williamson Ether Synthesis
In the Williamson ether synthesis, metal alkoxides react with primary alkyl halides and tosylates by an SN2 pathway.
There are two variations of the Williamson ether
A1.    Alcohols are reacted with a strong base to produce the alkoxide ion, which then reacts with halide or tosylate.
                    (1)  NaH
     R-OH     ---------------------------------->   R-O-R'
                   (2)  R'X  (1o halide or tosylate)
 

                           (1)  NaH
    t-Bu-OH     ------------------>  t-Bu-O-CH3
                           (2)  CH3-I

A2.    Silver oxide, Ag2O, can be used instead of the strong base.  No need to generate metal alkoxide intermediate.
                                          Ag2O
    t-Bu-OH  +  CH3-I  ---------------->  t-Bu-O-CH3

B.    Alkoxymecuration of Alkenes
        (CF3CO2)2Hg        (Mercuric trifluoroacetate)
        Markovikov addition of the alcohol to the alkene.

                         1.  (CF3CO2)2Hg , Alcohol
        Alkene --------------------------------------> Ether
                         2. NaBH4

                                    1. (CF3CO2)2Hg , EtOH
        Cyclohexene -------------------------------------> Cyclohexyl ethyl ether
                                    2. NaBH4

Reactions of Ethers
A.    Acidic Cleavage
    Ether + HX -----> Alkyl halide + Alcohol
        HX = HI or HBr (HCl does not work.)
        Halide attacks at less hindered site to produce alkyl halide.
            Ethyl phenyl ether + HBr/Heat/Water ----> Phenol + Bromoethane
            Ethyl isopropyl ether + HI/Heat/Water -----> Isopropyl alcohol + Iodoethane

B.    Reactions of Ethers: Claisen Rearrangement
        Claisen rearrangement is specific to allyl aryl ethers, Ar-O-CH2-CH=CH2.
Treatment of phenoxide ion with 3-bromopropene (allyl bromide) results in a Williamson ether synthesis and production of an allyl phenyl ether.

                       1. NaH/THF
       Ar-OH --------------------------------> Ar-O-CH2-CH=CH2 (Allyl phenyl ether)
                       2.  Br-CH2-CH=CH2
Heating the allyl phenyl ether to 200-250oC then effects Claisen rearrangement, leading to an o-allylphenol.

Epoxides
Common cyclic ethers
THF (C4H8O) 1,4-Dioxane (C4H8O2)

Epoxides (oxiranes) are three-membered cyclic ethers.

Synthesis of Epoxides
A.    Industrial ethylene oxide production:    Ethylene + Air/ Silver oxide ------ > Ethylene oxide

B.     Alkene + peroxyacid, RCO3H ---- > Epoxide.       [m-Chloroperoxybenzoic is the peroxyacid most commonly used.]

C.    Alkene + Cl2/H2O ---> Halohydrin + NaOH/H2O -----> Epoxide + Water + NaCl

Ring-Opening Reactions of Epoxides
A.  Acid-catalyzed
        Epoxide + HX/Ether -----> halohydrin    [X bonds at least hindered in carbon in 1o and 2o but most in 3o]

B.  Base-catalyzed
B1a.    Epoxide + Hydroxide -----> diol      [base attack at less hindered site]

B1b.    Epoxide + Alkoxide -----> alkoxyalcohol      [base attack at less hindered site]

B2.    Epoxide + Grignard -----> alcohol with extended carbon chain

Crown Ethers
Crown ethers are cyclic polyethers.

Formula x-crown-y where x = total number of atoms in the ring and y is the number of oxygen atoms.

Crown ethers solvate metal cations by sequestering the metal in the center of the polyether cavity.

Result is a "naked" anion which can be carried into organic solution in aprotic conditions.

Spectroscopy of Ethers
Ethers are difficult to distinguish by IR.

NMR of carbon and protons are shifted downfield.

Thiols and Sulfides
Thiols are sulfur analogs of alcohols. R-SH

Thiol Nomenclature
The rules for naming thiols are exactly like those for alcohols, except that the suffix -ol is replaced by -thiol. The SH group is itself is referred to as a mercapto group.

trans-2-Butene-1-thiol (North American skunk spray) 

Sulfides are sulfur analogs of ethers.      R-S-R
Sulfide Nomenclature
Sulfides are named by following the same rules used for ethers, with sulfide used in place of ether.
CH3-S-CH3                     CH3CH2-S-CH2CH2CH3
Dimethyl sulfide       Ethyl propyl sulfide

Thiol Synthesis
A.    Alkyl halide + hydrosulfide anion ------> Thiol
CH3-CH2-CH2-Br + NaSH ------->  1-propanethiol

B.    Best method is to treat an alkyl halide with thiourea and then follow with hydrolysis conditions.
                        (1)  Thiourea [CS(NH2)3]
Alkyl halide  ------------------------------------>  Thiol
                        (2)  NaOH, H2O

                                 (1)  Thiourea [CS(NH2)3]
CH3-CH2-CH2-Br ------------------------------------->  1-propanethiol
                                 (2)  NaOH, H2O

Thiol Reactions
Thiols are oxidized by bromine or iodine to yield disulfides, RSSR.

                    I2
2 R-SH ---------------> R-S-S-R
  thiol      Zn, H+         disulfide

Sulfide Synthesis
Thiols react with strong bases to give the corresponding thiolate anion, RS-.  These ions react with 1o or 2o halides to give sulfides.
             (1)  NaH
Thiol  --------------------------->  Sulfide
             (2)  1o or 2o Halide

                                (1)  NaH
     Ph-SH           ------------------->   Ph-S-CH3
Benzene Thiol      (2)  CH3I          Methyl phenyl sulfide

Sulfide Reactions
A.    Dialkyl sulfides react with 1o alkyl halides to produce trialkylsulfonium salts (R3S+).
                                         THF
CH3-S-CH3 +   CH3I  ------------->   (CH3-)3S+I-
                                                            Trimethylsulfonium iodide

B.    Sulfides can be oxidized to sulfoxides (R2SO) and sulfones (R2SO2).
                       H2O2 , H2O                                                               CH3O3H
Ph-S-CH3  ------------------------->      Ph-SO-CH3                     ------------------->   Ph-SO2-CH3
                                                       Methyl phenyl sulfoxide                                   Methyl phenly sulfone

Suggested problems
17.24, 17.25, 17.26, 17.27, 17.28, 17.29, 17.31, 17.32, 17.33, 17.34, 17.37, 17.38, 17.39, 17.47, 17.49,
17.54, 17.56, 17.57, 17.58, 17.59, 17.60, 17.61, 17.61, 17.62

18.25,  18.26,  18.27,  18.28,  18.29, 18.52, 18.53, 18.54