Mechanisms of organic reactions

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Mechanisms of organic reactions

• mirka.rovenska_at_lfmotol.cuni.cz

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Types of organic reactions

• Substitution an atom (group) of the molecule is
  replaced by another atom (group)
• Addition p-bond of a compound serves to create
  two new covalent bonds that join the two
  reactants together
• Elimination two atoms (groups) are removed from
  a molecule which is thus cleft into two products
• Rearrangement atoms and bonds are rearranged
  within the molecule thus, isomeric compound is
  formed

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Mechanism

• A reaction can proceed by
• homolytic mechanism each fragment possesses one
  of the bonding electrons thus, radicals are
  formed
• AB ? A B
• heterolytic mechanism one of the fragments
  retains both the bonding electrons thus, ions
  are formed
• AB ? A B

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Agents

• Radical possess an unpaired electron (Cl)
• Ionic
• A) nucleophilic possess an electron pair that
  can be introduced into an electron-deficient
  substrate
• i) anions (H, OH)
• ii) neutral molecules (NH3, HOH)
• B) electrophilic electron-deficient ? bind to
  substrate centres with a higher electron density
  
• i) cations (Br)
• ii) neutral molecules (for example Lewis acids
  AlCl3)

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Lewis acids and bases

• Lewis base acts as an electron-pair donor e.g.
  ammonia NH3
• Lewis acid can accept a pair of electrons e.g.
  AlCl3, FeCl3, ZnCl2. These compounds important
  catalysts generate ions that can initiate a
  reaction
• CH3Cl AlCl3 ? CH3 AlCl4-

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Radical substitution
- here lipid peroxidation

• 1. Initiation formation of radicals H2O ? OH
  H
• 2. Propagation radicals attack neutral
  molecules generating new molecules and new
  radicals
• CH3CH2R OH
  CH3CHR CH3COO
• 3. Termination radicals react with each other,
  forming stable products thus, the reaction is
  terminated (by depletion of radicals)

H
R
O2

H2O
fatty acid
CH3CH2R
CH3COOH
CH3CHR

H
R
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Electrophilic substitution

• An electron-deficient agent reacts with an
  electron-rich substrate the substrate retains
  the bonding electron pair, a cation (proton) is
  removed
• RX E ? RE X
• Typical of aromatic hydrocarbons
• chlorination
• nitration etc.

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Aromatic electrophilic substitution using Lewis
acids

• Halogenation
• Very often, electrophilic substitution is usedto
  attach an alkyl to the benzene ring(Friedel-Craft
  s alkylation)

benzene carbocation
bromobenzene
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Inductive effect

• Permanent shift of ?-bond electrons in the
  molecule composed of atoms with different
  electronegativity
• I effect is caused by atoms/groups with high
  electronegativity that withdraw electrons from
  the neighbouring atoms Cl, CO, NO2
• I effect is caused by atoms/groups with low
  electronegativity that increase electron density
  in their vicinity metals, alkyls

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Mesomeric effects

• Permanent shift of electron density along the
  ?-bonds (i.e. in compounds with unsaturated
  bonds, most often in aromatic hydrocarbons)
• Positive mesomeric effect (M) is caused by
  atoms/groups with lone electron pair(s) that
  donate p electrons to the system NH2, OH,
  halogens
• Negative mesomeric effect (M) is caused by
  atoms/groups that withdraw p electrons from the
  system NO2, SO3H, CO

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Activating/deactivating groups

• If inductive and mesomeric effects are
  contradictory, then the stronger one predominates
  
• Consequently, the group bound to the aromatic
  ring is
• activating donates electrons to the aromatic
  ring, thus facilitating the electrophilic
  substitution
• a) M gt I OH, NH2
• b) only Ialkyls
• deactivating withdraws electrons from the
  aromatic ring, thus making the electrophilic
  substitution slower
• a) M and I CO, NO2
• b) I gt Mhalogens

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Electrophilic substitution M, I-effects

• Substituents exhibiting the M or I effect
  (activating groups, halogens) attached to the
  benzene ring direct next substituent to the
  ortho, para positions
• Substituents exhibiting the M and I effect
  (CHO, NO2) direct the next substituent to the
  meta position

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Nucleophilic substitution

• Electron-rich nucleophile introduces an electron
  pair into the substrate the leaving atom/group
  retains the originally bonding electron pair
• Nu RY ? NuR Y
• This reaction is typical of haloalkanes
• Nucleophiles HS, HO, Cl

alcohol is produced
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Radical addition

• Again initiation (creation of radicals),
  propagation (radicals attack neutral molecules,
  producing more and more radicals), termination
  (radicals react with each other, forming a stable
  product the chain reaction is terminated)
• E.g. polymerization of ethylene using dibenzoyl
  peroxide as an initiator

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Electrophilic addition

• An electrophile forms a covalent bond by
  attacking an electron-rich unsaturated CC bond
• Typical of alkenes and alkynes
• Markovnikovs rule the more positive part of the
  agent (hydrogen in the example below) becomes
  attached to the carbon atom (of the double bond)
  with the greatest number of hydrogens

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Nucleophilic addition

• In compounds with polar unsaturated bonds, such
  as CO
• Nucleophiles water, alcohols, carbanions form
  a covalent bond with the carbon atom of the
  carbonyl group

carbon atom carries ?
used for synthesisof alcohols
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Hemiacetals

• Addition of alcohol to the carbonyl group yields
  hemiacetal
• As to biochemistry, hemiacetals are formed by
  monosaccharides

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Elimination

• In most cases, the two atoms/groups are removed
  from the neighbouring carbon atoms and a double
  bond is formed (?-elimination)
• Elimination of water dehydration used to
  prepare alkenes
• In biochemistry e.g. in glycolysis

H2O
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Rearrangement

• In biochemistry often migration of a hydrogen
  atom, changing the position of the double bond
• Keto-enol tautomerism of carbonyl compounds
  equilibrium between a keto form and an enol form
• E.g. isomerisation of monosaccharides occurs via
  enol form

dihydroxyaceton- phosphate
glyceraldehyd- 3-phosphate
enol form