Chem 334 - Fall 2001
Organic Chemistry I
Dr. Carl C. Wamser

Chapter 4 Notes: Alcohols and Alkyl Halides

Functional groups

alkyl halide: R-X (X = halogen atom)

alcohol: R-O-H (hydroxyl group)

Functional Group Classification

• based on the carbon the X or OH group is attached to:
  1° , 2° , 3°
• ethyl alcohol
  CH3CH2OH (1°)
• isopropyl chloride
  (CH3)2CHCl (2°)
• t-butyl alcohol
  (CH3)3COH (3°)

Alkyl Halide Nomenclature

• halogen substituents are indicated by the prefixes fluoro-, chloro-, bromo-, and iodo- and listed in alphabetical order with other substituents
• common names - name the alkyl group followed by the name of the halide
  e.g., methyl chloride or chloromethane
• several polyhaloalkanes are common solvents and are generally referred to by their common names
  e.g., chloroform or trichloromethane, Freon 12 or dichlorodifluoromethane
• hydrocarbons in which all hydrogens are replaced by halogens are commonly named as perhaloalkanes
  e.g., perfluoroethane or 1,1,1,2,2,2-hexafluoroethane

Alcohol Nomenclature

• common name: alkyl alcohol
• IUPAC: alkanol
• OH group takes priority over substituents
  - it must be in the parent chain
  - the direction of numbering gives it the lower possible number (regardless of substituents)
• use -ol suffix with number designation
• name other substituents as prefixes as usual
• more than one alcohol named as a -diol, -triol, etc.

Alcohol Examples

cyclohexyl alcohol or cyclohexanol

trans-4-methylcyclohexanol

Structure of Alcohols

• sp3 O with two covalent bonds and two lone pairs
• The bond angle about oxygen is about 105°, explained as greater repulsions of the lone pairs towards the bonding pairs

Boiling Points of Alkyl Halides

• among constitutional isomers, branched isomers have a more compact shape, decreased area of contact, decreased van der Waals attractive forces between neighbors, and lower boiling points
  • 1-bromobutane (n-butyl bromide) bp = 100°
  • 2-bromo-2-methylpropane (t-butyl bromide) bp = 72°
• for an alkane and an alkyl halide of comparable size and shape, the alkyl halide has the higher boiling point
  the difference is due almost entirely to the greater polarizability of the three unshared pairs of electrons on halogen compared with the polarizability of shared electron pairs of the hydrocarbon
  • ethane bp = -89°
  • bromomethane bp = 4°
• boiling points of alkyl fluorides are lower than those of hydrocarbons of comparable molecular weight
  the difference is due to the small size of fluorine, the tightness with which its electrons are held, and their particularly low polarizability
  • 2-methylpropane bp = - 1°
  • 2-fluoropropane bp = - 11°

Polarity of Alkyl Halides

• dipole moment of RX depends on:
  the sizes of the partial charges,
  the distance between them, and
  the polarizability of the unshared electrons on halogen
• dipole moments of all the haloalkanes are comparable

Hydrogen Bonding

• attraction between the positive end of one dipole (an H bonded to F, O, or N - atoms of high electronegativity) and the negative end of a dipole, usually a lone pair on F, O, or N
• in alcohols, O lone pairs interact with polar H bonds
• covalent O-H bond strength ~ 100 kcal/mole
• O...H (H-bond) strength ~ 5 kcal/mole

Effects of H-Bonding

• alcohols have higher boiling points than alkanes (nonpolar) or alkyl halides (polar, but no H-bonds)
• ethers are polar but have no H-bonds
  (pentane and diethyl ether both boil at about 35°, but 1-butanol has a bp of 117°)
• H-bonds hold together the strands of DNA ("Velcro" effect)
• H-bonding increases water solubility

Review of Acid-Base Reactions

Bronsted-Lowry Acid/Base

• acid - donates H+
• base - accepts H+
  NH3 + H2O <==> NH4+ + OH-
  base + acid <==> acid + base
• note conjugate acid-base pairs
  (differ by H+)

Acidity Constant (Ka)

• HA + H2O <==> H3O+ + A-

usually simplified to
HA <==> H+ + A-

• Ka = [H+] [A-] / [HA]

Acid Strength (pKa)

• stronger acids have higher Ka
  for HCl, Ka = 10E7
  for CH3COOH, Ka = 10E-5
  (acetic acid, found in vinegar)
  
• pKa = - log Ka
• stronger acids have a lower pKa
  for HCl, pKa = -7
  for CH3COOH, pKa = 5

pH and pKa

• Ka = [H+][A-]/[HA]
• pKa = pH - log([A-]/[HA])
• for pH = pKa, [A- ] = [HA]
• for pH < pKa, HA predominates
• for pH > pKa, A- predominates
  e.g., for acetic acid at pH = 7
  [CH3COO-] > [CH3COOH]

Structural Effects on Acid Strength

• electronegativity
  HF > H2O > NH3 > CH4
• weaker bond to H
  HI > HBr > HCl > HF
• inductive effects - electron withdrawal
  H2SO4 > H2SO3
  Cl-CH2-COOH > CH3-COOH
• hybridization with greater s-character
  sp C-H > sp2 C-H > sp3 C-H
• delocalization
  RCOOH > ROH

Acid-Base Reactions

CH3COOH + OH- <==> CH3COO- + H2O
acid (pKa = 5) + base <==> base + acid (pKa = 15.7)
reaction favored for stronger acid

reaction favored to the right

Lewis Acids

• acid - accepts an electron pair
• base - donates an electron pair
  (making a new covalent bond)

Acid-Base Reactions of Alcohols

• remember analogy with water
• reactions as bases:
  H2O + H+ <==> H3O+
  ROH + H+ <==> ROH2+ (an oxonium ion)
• reactions as acids:
  H2O + B- <==> B-H + OH-
  ROH + B- <==> B-H + RO- (an alkoxide ion)

Mechanism of Proton Transfer - Potential energy diagram

• potential energy (delta H or delta G) vs reaction progress (or reaction coordinate)
• features of a typical potential energy diagram: transition state, delta H, Ea

Acidity of Alcohols

• alcohols about as acidic as water
  MeOH more acidic, EtOH less acidic
  3° alcohols much weaker acids
• pKa values: 3° > 2° > 1° > MeOH
  18 , 17, 16, 15.5 (compare H2O: pKa = 15.7)
• tBuOH + NaOH ---> unfavorable

Substitution Reactions with HX - SN1 Mechanism

• halide substitution by a three-step (SN1) mechanism
  tBuOH + HBr --> tBuOH2+ --> tBu+ --> tBuBr
• acid-base reaction sets up H2O as a good leaving group
• carbocation (3°) intermediate
• Br- as a nucleophile
• potential energy diagram
• rate-determining step is formation of the carbocation

Carbocations

• structure: trivalent sp2 C with only 6 electrons (electron-deficient)
• stability order: favored by electron donation by substituents
  3° > 2° > 1°

Reactivity

• alcohol reactivity parallels carbocation stability: 3° > 2° > 1°
• more stable intermediate (carbocation) implies a lower Ea (more stable transition state)

Hammond's Postulate

• What does a transition state look like?
  • a transition state looks like something between reactants and products
    but closer in structure to whichever it is closer in energy to
• Hammond's Postulate: the structure of the transition state
  for an exothermic reaction looks more like the reactants of that step
  for an endothermic reaction looks more like the products of that step
• for the SN1 substitution, the rate-determining step is formation of the carbocation (endothermic)
• transition states look mainly like a carbocation (and are more stable if the carbocation is more stable)

Substitution Reactions with HX - SN2 Mechanism

• 1° and methyl alcohols don't form stable carbocations, don't do SN1 well
  MeOH + HBr --> MeOH2+ Br- --> MeBr + H2O
  concerted displacement of H2O by Br- (bimolecular)

Halogen Substitution with Other Reagents

• PBr3 + alcohol gives alkyl bromide, with less rearrangement than with HBr
• SOCl2 + alcohol gives alkyl chloride, also with less rearrangement

Halogenation of Alkanes

Free Radicals

• radical: any chemical species that contains one or more unpaired electrons
• radicals are formed by homolytic cleavage of a bond
• a barbed curved (fishhook) arrow is used to show the change in position of a single electron
• the order of stability of alkyl radicals is 3° > 2° > 1° > CH3
• radical initiators like peroxides (ROOR) have weak bonds, eaily broken

Mechanism - Chain initiation

• a step in a radical chain reaction characterized by formation of radicals from nonradical compounds
  • Cl2 --> 2 Cl.

Mechanism - Chain propagation

• a step in a radical chain reaction characterized by reaction of a radical and a molecule to form a new radical
  • Cl. + CH3CH3 --> CH3CH2. + HCl
  • CH3CH2. + Cl2 --> CH3CH2Cl + Cl.
• notice that the radicals recycle
• chain length, n: the number of times the cycle of chain propagation steps repeats in a chain reaction

Mechanism - Chain termination

• a step in a radical chain reaction that involves destruction of radicals
  • 2 Cl. --> Cl2
  • CH3CH2. + Cl. --> CH3CH2Cl
  • 2 CH3CH2. --> CH3CH2CH2CH3

Energetics

• using BDE data, calculate the heat of reaction, delta H°, for the halogenation of an alkane
• delta H = sum of bonds broken - sum of bonds made

Halogenation of Larger Alkanes

• regioselectivity of 2° hydrogen over a 1° hydrogen is high for bromination
  • propane + Br2 --> 1-bromopropane (8%) + 2-bromopropane (92%)
• regioselectivity is not as high for chlorination
  • propane + Cl2 --> 1-chloropropane (43%) + 2-chloropropane (57%)
• regioselectivity is 3° > 2° > 1°
  for bromination - approximately 1600:80:1
  for chlorination - approximately 5:4:1
• predict products based on regioselectivity (energetic factor) x statistical factor (number of H's)
• example: draw all monobromination products for isobutane and predict the % of each for a given reaction

Regioselectivity

• the regioselectivity of chlorination and bromination
  can be accounted for in terms of the
  relative stabilities of alkyl radicals (3° > 2° > 1° > methyl)
• how do we account for the greater regioselectivity of
  bromination (1600:80:1) compared with chlorination (5:4:1)?

Hammond's Postulate

• in halogenation of an alkane, the rate-limiting step is hydrogen abstraction
  this step is exothermic for chlorination and endothermic for bromination
• because hydrogen abstraction for chlorination is exothermic,
  the transition state resembles the alkane and a chlorine atom,
  there is little radical character on carbon in the transition state, and
  regioselectivity is only slightly influenced by radical stability
• because hydrogen abstraction for bromination is endothermic,
  the transition state resembles an alkyl radical and HBr,
  there is significant radical character on carbon in the transition state, and
  regioselectivity is greatly influenced by radical stability.

Radical stability

• 3° > 2° > 1° > methyl
  • 3° C-H bond 91 kca/mol
  • 2° C-H bond 95 kca/mol
  • 1° C-H bond 98 kca/mol
• regioselectivity is in the same order
• the order is like carbocation stability and for a similar reason -
  the radical center is electron-deficient and needs electron donation