7.11 Chiral Molecules with Two Chirality Centers

1
Alkynes
2
Alkynes

• Hydrocarbons with a carboncarbon triple bond are
  alkynes. Noncyclic alkynes have the molecular
  formula CnH2n-2.
• Acetylene (HC?CH) is the simplest alkyne.
• Compounds with the triple bond at the end of a
  carbon
• chain (RC?CH) are monosubstituted, or terminal,
  alkynes.
• Disubstituted alkynes (RC?CR') have internal
  triple bonds.

3
Sources of Alkynes

• In the late 19th century calcium carbide was
  formed by heating coke and limestone.

The calcium carbide was hydrolysed to form
acetylene.
4
Sources of Alkynes

• One alternative synthesis is the dehydration of
  ethylene.
• The endothermic reaction favors acetylene at high
  temperature.

Enzymes known as acetylenases catalyze this
reactionin nature.
5
Naturally Occurring Alkynes

• Some bacteria produce dynemicin A which has
  been shown to cleave DNA.

Diacetylene has been identified asa component of
the atmospheresof Uranus, Neptune and Pluto.
Some fatty acids contain an alkyne, e.g.
stearolic acid.
6
Naming Alkynes

• Replace the suffix ane for the corresponding
  alkane with yne.

7
Naming Alkynes

• Compounds that contain both an alkene and an
  alkyneare numbered to give the first multiple
  bond the lowest number and are named as an
  enynes.

hept-1-en-5-yne
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Physical Properties of Alkynes

• Alkynes resemble alkanes and alkenes in physical
  properties.Low density and low water
  solubility.Boiling points similar to the
  corresponding alkane.

9
Structure of Alkynes

• Acetylene is linear.

Cyclononane, the smallest stable cycloalkyne is
strainedas the C-C?C-C unit is clearly bent.
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Bonding in Alkynes

• The C?C has two p-bonds and one s-bond. The
  s-bond is formed by overlap of sp orbitals. The
  p-bonds areformed by overlap of p orbitals. The
  p-bonds are
• orthogonal to each other shown in (b) and (c).

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Bonding in Alkynes

• The electrostatic potential maps shows the high
  electron density (red) associated with the
  p-bonds.

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Bonding in Alkanes, Alkenes and Alkynes
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Bonding in Alkanes, Alkenes and Alkynes
For the series ethane ? ethylene ? acetylene the
general trends are 1. The geometry at carbon
changes from tetrahedral ? trigonal planar
? linear. 2. The C-C and C-H bonds become
shorter and stronger. 3. The acidity of the C-H
bonds increases.
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C-H Bond Lengths

• C-H bond lengths are shortest for hydrogens
  bonded toa sp C. The sp orbital has higher s
  character than sp2 orbitals so it is closer to
  the carbon atom.

15
Acidity of Alkanes, Alkenes and Alkynes

• C-H bonds of alkanes, alkenes and alkynes are
  very weak acids. The pKa of methane is estimated
  to be 60.

Because it is derived from a very weak acid the
conjugate base, a carbanion, is a very strong
base.
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Acidity Trend

• The effective electronegativity of carbon
  increases with increasing s-character
  (sp3gtsp2gtsp) therefore the pKa decreases in the
  same order.

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Acidity of Alkynes
Terminal alkynes RC?CH are similar to acetylene
in acidity.

• After deprotonation the acetylide electron pair
  is in a sp orbital.

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Acid-Base Reactions of Alkynes

• In order to form the acetylide anion the base
  must bestrong enough. The conjugate acid of the
  base should have pKa greater than the pKa of the
  alkyne.Hydroxide is too weak and the
  equilibrium lies to the left.

Amide is strong enough and the equilibrium lies
to the right.
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Preparation of Alkynes by Alkylation of
Acetylene and Terminal Alkynes
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Acetylide Anions as Nucleophiles

• Acetylide anions react with methyl and primary
  alkyl halides to form substituted alkynes.

This is an SN2 type of reaction.
21
Acetylide Anions as Nucleophiles
Examples include
The reagents are listed above and below the
reaction arrow in the order they are used. So,
in the first reaction,acetylene is first
deprotonated with sodium amide in ammonia and
then reacted with ethyl bromide.
22
Elimination Reactions with Acetylide Anions

• Acetylide anions are very basic so they act as
  bases if the alkyl halide is secondary or
  tertiary.

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Preparation of Alkynes by Elimination

• Alkynes can be prepared by double
  dehydrohalogenation of either geminal dihalides
  or vicinal dihalides.

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Preparation of Alkynes by Elimination

• Three equivalents of base are required if the
  alkyne is terminal since a terminal alkyne is
  deprotonated by the base as soon as it is
  formed. Protonation of the acetylide anion is
  then required as a second step.

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From Alkenes to Alkynes

• Vicinal dibromides are formed on bromination of
  an alkene so this gives us a way to transform an
  alkeneinto an alkyne.

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Reactions of Alkynes

• Reactions of alkynes are similar to reaction of
  alkeneshydrogenation, hydration, halogenation,
  ozonolysis.

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Hydrogenation of Alkynes

• Alkynes are reduced to alkanes using hydrogen and
  a transition metal catalyst.

For example
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Relative Stability of Alkynes

• The heat of hydrogenation of 1- and 2-butyne can
  be used to determine the relative stability of
  an internal and a terminal alkyne (both yield
  butane as product).

Less heat is released by 2-butyne so that is the
more stable isomer.
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Stereochemistry of Hydrogenation

• Metal catalyzed hydrogenation is a syn addition
  process.

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Hydrogenation with Lindlars Catalyst

• Lindlars catalyst is a partially deactivated
  catalyst that
• was developed for partial hydrogenation of
  alkynes to alkenes.

Disubstituted alkynes yield cis-alkenes.
31
Metal-Ammonia Reduction of Alkynes

• Group I metals in liquid ammonia reduce alkynes
  to trans alkenes exclusively.

The key intermediate is the vinyl radical which
prefers theless hindered trans conformation.
32
Mechanism of Metal-Ammonia Reduction
Sodium atoms dissolved in liquid ammonia
dissociate into sodium ions and electrons, both
solvated by ammonia. The solvated electrons are
represented in e(am).

• Step 1. Electron transfer.

Step 2. Proton transfer.
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Mechanism of Metal-Ammonia Reduction

• Step 3. Electron transfer.

Step 4. Proton transfer.
34
Addition of Hydrogen Halides

• Hydrogen halides add to alkynes to form alkenyl
  halides.

The reaction follows Markovkovs Rule (the proton
adds to the carbon that initially has the most
hydrogens).
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Mechanism of Addition to Alkynes

• Markovnikov addition suggests formation of a
  vinyl cation

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Mechanism of Addition to Alkynes

• Kinetics studies however suggest the involvement
  of two equivalents of HX rate
  kalkyneHX2
• A possible mechanism is

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Addition of HX to Alkynes

• Excess HX leads to geminal dihalides.

Since each addition of HX follows Markovnikovs
ruleboth protons are added to the same carbon.
38
Free Radical Addition of HBr

• Anti-Markovnikov addition of HBr is performed
  with peroxide initiation.

39
Hydration of Alkynes

• Hydration of alkynes yields a special alcohol
  an enol. The enol has an OH attached to an
  alkene carbon.

The enol rapidly isomerizes to the keto form.
This equilibration is keto-enol
tautomerism. Tautomers are constitutional
isomers that equilibrate bymigration of an atom
or group.
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Mechanism of Conversion of an Enol to a Ketone

• Step 1. Protonation.

Resonance forms
Step 2. Deprotonation.
41
Hydration of Alkynes

• In general the keto form is more stable so it
  will be drawnas the product of a hydration
  reaction.

The reaction follows Markovnikovs rule so
terminal alkynes yield methyl ketones not
aldehydes.
42
Addition of Halogens to Alkynes

• Two molecules of halogen react with one alkyne to
  yielda tetrahaloalkane.

43
Addition of Halogens to Alkynes

• An anti dihaloalkene can be isolated if exactly
  one equivalent of halogen is used.

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What Could be Made From Acetylene but Isnt

• We can write simple reactions to produce these
  usefulmonomers from acetylene.

In reality they are actually made from ethylene
because itis so much cheaper and easier to
prepare than acetylene!
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Ozonolysis of Alkynes

• Ozonolysis also cleaves alkynes. The alkyne
  carbons are tranformed into carboxylic acid
  carbons. The end carbon of a terminal alkyne
  becomes carbonic acid which dissociatesto CO2
  and H2O.

46
Alkynes in Synthesis and Retrosynthesis
47
Applications of Alkynes in Synthesis
Example Outline a synthesis of 1,2-epoxybutane
using ethyl bromide and acetylene as sources for
all the carbon atoms.
The epoxide may be formed from the corresponding
alkene
The alkene could be made from the corresponding
alkyne which could itself be prepared from an
acetylide anion
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Applications of Alkynes in Synthesis
Now list the reactions in the forward direction
starting from acetylene.