Effect of the Nucleophile  Author: Dr. Robert D. Craig,
This is                     Doug Henning!He performed his first show at the age of 14 at the birthday party of a friend  a...
He won The Tony Award   Debuting in December 1975, Doug    Hennings World of Magic captured    the attention of more than...
Hughes and Sir Christopher           IngoldIn 1935, Edward D. Hughes and  Sir Christopher Ingold studied  nucleophilic sub...
Are just as spectacular!!!!!The two main mechanisms are the SN 1 reaction and the SN2 reaction.The “S” stands for chemical...
Sir Christopher Ingold   Known for Organic reaction    mechanisms      “Cahn-Ingold-Prelog” rules !He received the Longs...
Just like Paul Macartney!!!
Sir Christopher Ingold Is one bad dude!!!!!
This is how he got down!!!A graph showing the relative reactivities of the different     alkyl halides towards SN1 and SN2...
the SN1 reaction
the SN2 reaction
Effect of the Nucleophile   The nucleophile takes part in the    slow step (the only step) of the SN2    reaction but not...
Effect of the Nucleophile   Weak nucleophiles fail to promote    the SN2 reaction; therefore, reactions    with weak nucl...
Effect of the Nucleophile   SN1:  Nucleophile strength is    unimportant (usually weak).
Effect of the Nucleophile   SN2:   Strong nucleophiles are    required.
Effect of the Substrate   The structure of the substrate (the    alkyl halide) is an important factor in    determining w...
Effect of the Substrate   Methyl halides and primary halides    cannot easily ionize and undergo SN1    substitution beca...
Tert-butyl-chloride-3D   Tertiary halides are too hindered to    undergo SN2 displacement, but they    can ionize to form...
Tert-butyl-chloride-3Dwill exhibit Steric hinderance
SN2 substrates   SN2 substrates:CH3X > 1° > 2°   (3° is not suitable
SN1 substrates   SN1 substrates:    3° > 2°(1° and CH3X are unlikely)
silver nitrate (AgNO3)   If silver nitrate (AgNO3) is added to    an alkyl halide in a good ionizing    solvent, it remov...
Effect of the Solvent   The slow step of the SN1 reaction    involves formation of two ions.    Solvation of these ions i...
Effect of the Solvent   Less charge separation is generated    in the transition state of the SN2    reaction.   Strong ...
Effect of the Solvent   Thus, the SN2 reaction often goes    faster in less polar solvents if the    nucleophile will dis...
Effect of the SolventThe slow step of the SN1 reaction involves formation of two ions. Solvation of these ions is crucial ...
Effect of the Solvent   The solvent may be heated to reflux    (boiling) to provide the energy    needed for ionization
This is . . .   .
The same as this . . .
the transition state   Less charge separation is generated in the    transition state of the SN2 reaction. Strong    solv...
the transition state
the transition state   .
aprotic solvents:   Common characteristics of aprotic    solvents:   Examples are dimethyl sulfoxide,    dimethylformami...
dimethyl sulfoxideYou might see this later
dimethyl sulfoxide   .
tetrahydrofuran   .
tetrahydrofuran    You will definitely need this later.   .
Effect of the Solvent   Polar Protic Solvents   Lets start with the meaning of the adjective    protic. In the context u...
Effect of the Solvent   The large difference in electronegativities of the    oxygen and the hydrogen atom, combined with...
   http://myphlip.pearsoncmg.com/altprod
The slow step   The slow step of the SN1 reaction    involves formation of two ions.    Solvation of these ions is crucia...
The slow step   The solvent may be heated to reflux    (boiling) to provide the energy    needed for ionization.
The slow step   Less charge separation is generated in the    transition state of the SN2 reaction.    Strong solvation m...
less polar solvents   Thus, the SN2 reaction often goes    faster in less polar solvents if the    nucleophile will disso...
SN1   SN1: Good ionizing solvent required.
SN2   SN2: May go faster in a less polar    solvent
Kinetics   The rate of the SN1 reaction is    proportional to the concentration of    the alkyl halide but not the    con...
Kinetics   The rate of the SN2 reaction is    proportional to the concentrations of    both the alkyl halide [R—X] and th...
Kinetics   SN1 rate = kr[R—X]   SN2 rate = kr[R—X][Nuc: −]
Stereochemistry   The SN1 reaction involves a flat    carbocation intermediate that can be    attacked from either face. ...
Stereochemistry   The SN2 reaction takes place    through a back-side attack, which    inverts the stereochemistry of the...
Stereochemistry   SN1 stereochemistry:   Mixture of retention and inversion;    racemization.
Stereochemistry   SN2 stereochemistry   Complete inversion
Rearrangements   The SN1 reaction involves a    carbocation intermediate. This    intermediate can rearrange, usually    ...
Rearrangements   The SN2 reaction takes place in one    step with no intermediates.   No rearrangement is    possible in...
rearrangement reaction
An example of a reaction taking place with   an SN1 reaction mechanism is thehydrolysis of tert-butyl bromide with water  ...
a tert-butyl carbocation   Formation of a tert-butyl carbocation    by separation of a leaving group (a    bromide anion)...
http://en.wikipedia.org/wiki/SN1_re               action
The hydride shift   The mechanism for hydride shift    occurs in multiple steps that includes    various intermediates an...
The hydride shift
The hydride shift
rearrangement reaction   A rearrangement reaction is a broad    class of organic reactions where the    carbon skeleton o...
Rearrangements   SN1: Rearrangements are common.
Rearrangements   SN2: Rearrangements are impossible
Nucleophillic substitutions                     SN1:                    SN2:Promoting factors    weak nucleophiles are str...
the nucleophile competes . . .   In both reactions, the nucleophile competes with    the leaving group. Because of this, ...
good leaving groups   Very good leaving groups, such as    triflate, tosylate and mesylate,    stabilize an incipient neg...
good leaving groups   Very good leaving groups, such as    triflate, tosylate and mesylate,    stabilize an incipient neg...
good leaving groups
good leaving groups   Hydroxide and alkoxide ions are not    good leaving groups; however, they    can be activated by me...
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Ppt0000015 feed the flame[1]this one (2)

  1. 1. Effect of the Nucleophile Author: Dr. Robert D. Craig,
  2. 2. This is Doug Henning!He performed his first show at the age of 14 at the birthday party of a friend and was inspired by his audiences spellbound reaction
  3. 3. He won The Tony Award Debuting in December 1975, Doug Hennings World of Magic captured the attention of more than 50 million viewers!
  4. 4. Hughes and Sir Christopher IngoldIn 1935, Edward D. Hughes and Sir Christopher Ingold studied nucleophilic substitution reactions of alkyl halides and related compounds.They proposed that there were two main mechanisms at work, both of them competing with each other.
  5. 5. Are just as spectacular!!!!!The two main mechanisms are the SN 1 reaction and the SN2 reaction.The “S” stands for chemical substitution,And the “N” stands for nucleophilic, and the number represents the kinetic order of the reaction.
  6. 6. Sir Christopher Ingold Known for Organic reaction mechanisms “Cahn-Ingold-Prelog” rules !He received the Longstaff Medal of the Royal Society of Chemistry in 1951, the Royal Medal of the Royal Society in 1952, and was knighted in 1958
  7. 7. Just like Paul Macartney!!!
  8. 8. Sir Christopher Ingold Is one bad dude!!!!!
  9. 9. This is how he got down!!!A graph showing the relative reactivities of the different alkyl halides towards SN1 and SN2 reactions
  10. 10. the SN1 reaction
  11. 11. the SN2 reaction
  12. 12. Effect of the Nucleophile The nucleophile takes part in the slow step (the only step) of the SN2 reaction but not in the slow step of the SN1. Therefore, a strong nucleophile promotes the SN2 but not the SN1.
  13. 13. Effect of the Nucleophile Weak nucleophiles fail to promote the SN2 reaction; therefore, reactions with weak nucleophiles often go by the SN1 mechanism if the substrate is secondary or tertiary
  14. 14. Effect of the Nucleophile SN1: Nucleophile strength is unimportant (usually weak).
  15. 15. Effect of the Nucleophile SN2: Strong nucleophiles are required.
  16. 16. Effect of the Substrate The structure of the substrate (the alkyl halide) is an important factor in determining which of these substitution mechanisms might operate.
  17. 17. Effect of the Substrate Methyl halides and primary halides cannot easily ionize and undergo SN1 substitution because methyl and primary carbocations are high in energy. They are relatively unhindered, however, so they make good SN2 substrates.
  18. 18. Tert-butyl-chloride-3D Tertiary halides are too hindered to undergo SN2 displacement, but they can ionize to form tertiary carbocations. Tertiary halides undergo substitution exclusively through the SN1 mechanism. Secondary halides can undergo substitution by either mechanism, depending on the conditions
  19. 19. Tert-butyl-chloride-3Dwill exhibit Steric hinderance
  20. 20. SN2 substrates SN2 substrates:CH3X > 1° > 2° (3° is not suitable
  21. 21. SN1 substrates SN1 substrates: 3° > 2°(1° and CH3X are unlikely)
  22. 22. silver nitrate (AgNO3) If silver nitrate (AgNO3) is added to an alkyl halide in a good ionizing solvent, it removes the halide ion to give a carbocation. This technique can force some unlikely ionizations, often giving interesting rearrangements (see Problem 6-29.)
  23. 23. Effect of the Solvent The slow step of the SN1 reaction involves formation of two ions. Solvation of these ions is crucial to stabilizing them and lowering the activation energy for their formation. Very polar ionizing solvents such as water and alcohols are needed for the SN1. The solvent may be heated to reflux (boiling) to provide the energy needed for ionization
  24. 24. Effect of the Solvent Less charge separation is generated in the transition state of the SN2 reaction. Strong solvation may weaken the strength of the nucleophile because of the energy needed to strip off the solvent molecules.
  25. 25. Effect of the Solvent Thus, the SN2 reaction often goes faster in less polar solvents if the nucleophile will dissolve. Polar aprotic solvents may enhance the strength of weak nucleophiles
  26. 26. Effect of the SolventThe slow step of the SN1 reaction involves formation of two ions. Solvation of these ions is crucial to stabilizing them and lowering the activation energy for their formation. Very polar ionizing solvents such as water and alcohols are needed for the SN1.
  27. 27. Effect of the Solvent The solvent may be heated to reflux (boiling) to provide the energy needed for ionization
  28. 28. This is . . . .
  29. 29. The same as this . . .
  30. 30. the transition state Less charge separation is generated in the transition state of the SN2 reaction. Strong solvation may weaken the strength of the nucleophile because of the energy needed to strip off the solvent molecules. Thus, the SN2 reaction often goes faster in less polar solvents if the nucleophile will dissolve. Polar aprotic solvents may enhance the strength of weak nucleophiles
  31. 31. the transition state
  32. 32. the transition state .
  33. 33. aprotic solvents: Common characteristics of aprotic solvents: Examples are dimethyl sulfoxide, dimethylformamide, dioxane and hexamethylphosphorotriamide, tetrahydrofuran
  34. 34. dimethyl sulfoxideYou might see this later
  35. 35. dimethyl sulfoxide .
  36. 36. tetrahydrofuran .
  37. 37. tetrahydrofuran You will definitely need this later. .
  38. 38. Effect of the Solvent Polar Protic Solvents Lets start with the meaning of the adjective protic. In the context used here, protic refers to a hydrogen atom attached to an electronegative atom. For our purposes that electronegative atom is almost exclusively oxygen. In other words, polar protic solvents are compounds that can be represented by the general formula ROH. The polarity of the polar protic solvents stems from the bond dipole of the O-H bond.
  39. 39. Effect of the Solvent The large difference in electronegativities of the oxygen and the hydrogen atom, combined with the small size of the hydrogen atom, warrant separating molecules that contain an OH group from those polar compounds that do not. Examples of polar protic solvents are water (H2O), methanol (CH3OH), and acetic acid (CH3CO2H).
  40. 40.  http://myphlip.pearsoncmg.com/altprod
  41. 41. The slow step The slow step of the SN1 reaction involves formation of two ions. Solvation of these ions is crucial to stabilizing them and lowering the activation energy for their formation. Very polar ionizing solvents such as water and alcohols are needed for the SN1.
  42. 42. The slow step The solvent may be heated to reflux (boiling) to provide the energy needed for ionization.
  43. 43. The slow step Less charge separation is generated in the transition state of the SN2 reaction. Strong solvation may weaken the strength of the nucleophile because of the energy needed to strip off the solvent molecules.
  44. 44. less polar solvents Thus, the SN2 reaction often goes faster in less polar solvents if the nucleophile will dissolve. Polar aprotic solvents may enhance the strength of weak nucleophiles.
  45. 45. SN1 SN1: Good ionizing solvent required.
  46. 46. SN2 SN2: May go faster in a less polar solvent
  47. 47. Kinetics The rate of the SN1 reaction is proportional to the concentration of the alkyl halide but not the concentration of the nucleophile. It follows a first-order rate equation.
  48. 48. Kinetics The rate of the SN2 reaction is proportional to the concentrations of both the alkyl halide [R—X] and the nucleophile [Nuc: −]. It follows a second-order rate equation.
  49. 49. Kinetics SN1 rate = kr[R—X] SN2 rate = kr[R—X][Nuc: −]
  50. 50. Stereochemistry The SN1 reaction involves a flat carbocation intermediate that can be attacked from either face. Therefore, the SN1 usually gives a mixture of inversion and retention of configuration
  51. 51. Stereochemistry The SN2 reaction takes place through a back-side attack, which inverts the stereochemistry of the carbon atom. Complete inversion of configuration is the result.
  52. 52. Stereochemistry SN1 stereochemistry: Mixture of retention and inversion; racemization.
  53. 53. Stereochemistry SN2 stereochemistry Complete inversion
  54. 54. Rearrangements The SN1 reaction involves a carbocation intermediate. This intermediate can rearrange, usually by a hydride shift or an alkyl shift, to give a more stable carbocation.
  55. 55. Rearrangements The SN2 reaction takes place in one step with no intermediates. No rearrangement is possible in the SN2 reaction.
  56. 56. rearrangement reaction
  57. 57. An example of a reaction taking place with an SN1 reaction mechanism is thehydrolysis of tert-butyl bromide with water forming tert-butyl alcohol
  58. 58. a tert-butyl carbocation Formation of a tert-butyl carbocation by separation of a leaving group (a bromide anion) from the carbon atom: this step is slow and reversible!
  59. 59. http://en.wikipedia.org/wiki/SN1_re action
  60. 60. The hydride shift The mechanism for hydride shift occurs in multiple steps that includes various intermediates and transition states. Below is the mechanism for the given reaction above:
  61. 61. The hydride shift
  62. 62. The hydride shift
  63. 63. rearrangement reaction A rearrangement reaction is a broad class of organic reactions where the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule [1] . Often a substituent moves from one atom to another atom in the same molecule. In the example below the substituent R moves from carbon atom 1 to carbon atom 2
  64. 64. Rearrangements SN1: Rearrangements are common.
  65. 65. Rearrangements SN2: Rearrangements are impossible
  66. 66. Nucleophillic substitutions SN1: SN2:Promoting factors weak nucleophiles are strong nucleophile needed OKNucleophile 3° > 2° CH3X > 1° >3° >2°substrate (RX) good ionizing solvent wide variety of needed solventsSolvent good ionizing solvent wide variety of needed solventsleaving group good one required good one requiredOther ***AgNO3You will use this! force ionization!
  67. 67. the nucleophile competes . . . In both reactions, the nucleophile competes with the leaving group. Because of this, one must realize what properties a leaving group should have, and what constitutes a good nucleophile. For this reason, it is worthwhile to know which factors will determine whether a reaction follows an SN1 or SN2 pathway.
  68. 68. good leaving groups Very good leaving groups, such as triflate, tosylate and mesylate, stabilize an incipient negative charge. The delocalization of this charge is reflected in the fact that these ions are not considered to be nucleophilic
  69. 69. good leaving groups Very good leaving groups, such as triflate, tosylate and mesylate, stabilize an incipient negative charge. The delocalization of this charge is reflected in the fact that these ions are not considered to be nucleophilic
  70. 70. good leaving groups
  71. 71. good leaving groups Hydroxide and alkoxide ions are not good leaving groups; however, they can be activated by means of Lewis or Brønsted acids

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