1. Alkyl Halides Preparation and Reactions
ORGANIC CHEMISTRY- 1
Alkyl Halides Preparation and Reactions BY
Dr. Sulaiman
Assistant Professor
UNIVERSITY OF NIZWA

2. RX = Alkyl halide INTRODUCTION
Alkyl halides, halogen-substituted alkanes are named systematically as Haloalkanes .
They are also known as Organohalides, compounds that contain one or more halogen atoms. Alkyl halides are widespread in nature, and over 5000 organohalides have been found in algae and various other marine organisms.
RX = Alkyl halide

3. Nomenclature

4. Alkyl Halides
Alkyl halides are organic molecules containing a halogen atom bonded to an sp3 hybridized carbon atom.
Alkyl halides are classified as primary (1°), secondary (2°), or tertiary (3°), depending on the number of carbons bonded to the carbon with the halogen atom.
The halogen atom in halides is often denoted by the symbol “X”.

5. Alkyl Halides
There are other types of organic halides. These include vinyl halides, aryl halides, allylic halides and benzylic halides.
Vinyl halides have a halogen atom (X) bonded to a C—C double bond (C=C-X).
Aryl halides have a halogen atom bonded to a benzene ring. (Ar-X).
Allylic halides have X bonded to the carbon atom adjacent to a C—C double bond. (C=C-C-X)
Benzylic halides have X bonded to the carbon atom adjacent to a benzene ring (Ar-C-X).

6. Preparation
1. Halogenation

7. Preparation

8. Preparation
2- Reaction with HX
HX is obtained from NaX + conc. H2SO4

9. Preparation
3- From alcohol 3 3

10. Preparation From alcohol – cont. ROH + HX  RX + H2O
ROH SOCl  RCl SO HCl
Pyridine (as solvent)
(This product is most easily purified)

11. Preparation
4- Diazonium coupling
From diazonium salt, you can make the following aryl halide:

12. Physical Properties
It has a little higher boiling point than corresponding alkane of comparable molecular mass. This is due to the dipole-dipole attraction between the molecules as they are polar.
CH3Cl, CH3Br and C2H5Cl are gases in room temperature while other members are liquids. Chlorobenzene is colourless liquid. All alkyl and aryl halides are insoluble in water due to the inability to form extensive H-bond with water molecules.

13. Chemical Properties
Hydrolysis – For phenol – industrial process

14. Chemical Properties Hydrolysis – cont.
Side product : alkene (From dehydrohalogenation)

15. Chemical Properties Formation of amine
If RX is in excess, further reaction is expected since RNH2 is an even stronger nucleophile.

16. Chemical Properties Formation of amine (cont.) RX + RNH2  R2NH + HX
RX + R2NH  R3N + HX
RX + R3N  R4N+ X-
Quarternary ammonium salt

17. Chemical Properties Formation of amine (cont.) Uunder normal condition
aryl halide is very difficult to have
nucleophilic substitution rx

18. Chemical Properties
Formation of nitrile

19. Chemical Properties
Formation of ether (Williamson’s synthesis)

20. Chemical Properties Formation of ester RX + R’COO- Ag+  R’COOR + AgX
Hydrolysis reaction (alcohol formation)

21. Chemical properties
Formation of Grignard Reagent
excess

22. Chemical properties
Wurtz Reaction
Wurtz – Fittig Reaction

23. Chemical properties Reaction with Grignard reagent alkane
What kind of reaction is this ?
How do you prepare :

24. Electronegativity
Electronegativity: the ability of an atom in a bond to pull on the electron. (Linus Pauling)
When electrons are shared by two atoms a covalent bond is formed.
When the atoms are the same they pull on the electrons equally. Example, H-H.
When the atoms are different, the atoms pull on the electrons unevenly. Example, HCl

25. Electronegativities of Some Elements
Element Pauling scale F
Cl 3.0 O N S C H
Na 0.9
Cs 0.7
Most electronegative element is F which is (EN 4.0).
Least electronegative stable element is Cs (EN 0.7).

26. Up to down Electronegativity decreases
Left to right Electronegativity increases

27. Substitution Reaction
The reaction in which one bond is broken and one bond is formed so that one group is substituted for another group. This is known as substantiation.
Nucleophilic Substitution Reaction
In which one nucleophile is substituted for another nucleophile.
Electrophilic Substitution Reaction
In which one electrophile is substituted for another electrophile

28. Nucleophilic Substitution Reactions
Nucleophilic Substitution (1896 by the German chemist
Paul Walden).
Halogen compounds are polar compounds. The
electron deficient carbon attach to the halogen is
susceptible to the attack of an electron rich
species (nucleophile) and undergo nucleophilic
substitution.

29. SN2 Reaction
SN2 reaction: It represents nucleophilic, bimolecular reaction, (Bimolecular means that two molecules i.e. nucleophile and alkyl halide, take part in the step whose kinetics are measured.)
Two species in the rate determine step
When Nu─ attacks on a substrate the breaking of old bond and formation of a new bond takes place simultaneously and the reaction proceed through the formation of transition state.
Transition state (T.S.) is a slow step and is called rate determing step.

30. The SN2 Reaction Methyl group is small
Sterically accessible compounds react by this mechanism!!
Methyl group is small
Mechanism - Bimolecular Nucleophilic Substitution [SN2] -
Transition state (trigonal bipyramidal)

31. Chemical Properties -
Transition state

32. Chemical Properties Bimolecular:
Molecularity refers to the number of species that are undergoing bond-making and/or bond-breaking process in the rate determining step.
Rate = k [alkyl halide]1 [OH-]1
Second order reaction
If concentration of any of the two species is doubled the rate of reaction will be doubled and if conc. of both the substrate and nucleophile is doubled the rate of reaction will increases four times.

33. SN2 Reaction: stereochemistry.. _ : 3 C B r H E t O ( S ) - e n a i o m .. H O C E t Br _ + 3
(R) enantiomer
For an SN2 Reaction:
Walden Inversion: Inversion of configuration S to R and R to S in SN2 reactions, observed by Paul Walden 1896.
Inversion of configuration

34. SN2 Reaction: substrate structure
Reactivity order---- fastest to slowest!

35. Inversion of configuration
Predicting the Stereochemistry of a Nucleophilic Substitution Reaction (Stereo specific reaction)
Inversion of configuration

36. The Substrate: Steric Effects in the SN2 Reaction
Hindered and bulky substrate prevent easy approach of the nucleophile, making bond formation difficult.
The transition state of a sterically hindered substrate, is higher in energy and forms more slowly than the corresponding transition state for a less hindered substrate.

37. The Nucleophile
Any species, either neutral or negatively charged, can act as a nucleophile as long as it has an unshared pair of electrons; that is, as long as it is a Lewis base.
Nucleophilicity” is usually taken as the affinity of a Lewis base for a carbon atom in the SN2 reaction and “basicity” is the affinity of a base for a proton. Thus a nucleophile attacks on carbon (C) while base attacks on proton (H+) in SN2 reactions.

38. leaving group
Since the leaving group is expelled with a negative charge in most SN2 reactions, the best leaving groups are those that best stabilize the negative charge in the transition state.
The greater the extent of charge stabilization by the leaving group, the lower the energy of the transition state and the more rapid the reaction.

39. In a reaction, the exact nucleophilicity of a species depends on the substrate, the solvent, and the reactant concentrations.
• Nucleophilicity usually increases going down a column of the periodic table. Thus, H2S is more nucleophilic than H2O, and the halide reactivity
order is I2> Br2> Cl2.

40. Down the periodic table, elements have their valence electrons less tightly held, and consequently more reactive. The nucleophilicity order can change depending on the solvent.
• Negatively (─ve) charged nucleophiles are usually more reactive than neutral ones. As a result, SN2 reactions are often carried out under basic
conditions rather than neutral or acidic conditions.

41. SN1 properties
Mechanism - Unimolecular Nucleophilic Substitution [SN1]
Unimolecular because in rate determining step, only one molecule is involved.
Rate = k [alkyl halide]1 [OH-]0
Rate = k [R-Br]1
Thus it follows first order (unimolecular) kinetics.

42. The SN1 Mechanism
carbocation

43. Chemical Properties
intermediate

44. SN1 Reaction: stereochemistry
With chiral R-X compounds, the product will be racemic (50% of each enantiomer).
Racemization
Racemization is the conversion of one enantiomer in a 50:50 mixture of the two enantiomers (+ and −, or R and S) of a substance.
Racemization is normally associated with the loss of optical activity over a period of time since 50:50 mixtures of enantiomers are optically inactive.

45. SN1 Reaction Racemization

46. Factors affecting choice of mechanism
Structure of alkyl halide
3ry ry ry CH3
SN SN2
Use of 3ry alkyl halide favour SN1 since:

47. Factors affecting choice of mechanism
Use of 3ry alkyl halide favour SN1 since:
Alkyl groups hinder the approach of a nucleophile
(OR steric crowding at T.S. would destabilise a bimolecular transition state, thus increase the EA.)
is less
stable than
Not favour SN2
Favour SN2

48. Factors affecting choice of mechanism
Solvent
Highly polar (ionising) solvent favour SN1 (because forming ion in 1st step)
Polar solvent: aqueous, THF
Less polar solvent: alcoholic

49. Chemical Properties Factors affecting choice of mechanism
Choice of nucleophile
Strong nucleophile in high conc. favour SN2 while weak nucleophile in dilute solution favour SN1.
Strong nucleophile Weak nucleophile
OH H2O
NH NH3
CN HCN
RO ROH
Presence of Ag+ ion favour SN1

50. Summary of SN reaction -
Unimolecular nucleophilic Substitution (SN1)
Bimolecular nucleophilic Substitution (SN2)
2 steps:
1 step:

51. Summary of SN reaction -
Unimolecular nucleophilic Substitution (SN1)
Bimolecular nucleophilic Substitution (SN2)
Rate = k [alkyl halide]
Rate = k [alkyl halide] [Nu-]
Carbonium ion formed as intermediate (stabilized by inductive effect)
No intermediate carbonium ions but only transition states are involved.
Usually occur with tertiary alkyl halide
Usually occur with primary alkyl halide
Energy profile: 2 peaks
Energy profile: 1 peak

52. Summary of SN reaction -
Unimolecular nucleophilic Substitution (SN1)
Bimolecular nucleophilic Substitution (SN2)
Because of the equal chance of attack from both sides of carbonium ions, a racemic mixture of enantiomers obtained, i.e. optically inactive.
Configuration of the carbon centre attacked inverted (inversion of configuration). If the original alkyl halide is optically active, optically active product will be obtained.
Rate of Rx: PhCH2X > RCH=CHCH2X > 3o > 2o > 1o
Rate of Rx: 1o > 2o > 3o

53. Vinyl and Phenyl Compounds

54. ALKYL HALIDES Predict SN1 and SN2
This is SN1 reaction because the substrate is secondary and benzylic, the nucleophile is weakly basic, and the solvent is protic.
(b) This is SN2 reaction because the substrate is primary, the nucleophile is a reasonably good one, and the solvent is polar aprotic.

55. SNi Mechanism Aliphatic Nucleophilic substitution reaction leading to
retention of configuration (Internal Nucleophilic substations).
The displacement of -OH by Cl- using thionyl chloride.
This substitution proceeds through SNi Mechanism, in
which there is retention of configuration.
The reaction follows Second order kinetic
Rate α [R3C-OH] [SOCl2]

57. Neighboring group Participation (NGP) (Retention of configuration)
In first step of the reaction the neighboring group acts as nucleophile pushing out the leaving group.
In the 2nd step external nucleophile pushing out the neighboring group.

58. Neighboring group Participation (NGP)
The first step is the conversion of the OH to the corresponding alkoxide. This ion (alkoxide) act as nucleophile. It attacks the carbon carrying chlorine from the back side. This is an internal SN2 reaction and result in the inversion of configuration. Second SN2 inversion results in retention of configuration.
A classic example of NGP is the reaction of a sulfur or nitrogen mustard or (halide) with a nucleophile, the rate of reaction is much higher for the sulfur mustard and a nucleophile than it would be for a primary alkyl chloride without a heteroatom.
Cl-CH2-CH2-S-CH2-CH2

59. Substitution and Elimination
Two kinds of reactions can take place when a nucleophile
/Lewis base reacts with an alkyl halide.
The nucleophile can either substitute for the halide by reaction at carbon or can cause elimination of HX by reaction at a neighboring hydrogen.
Elimination reactions are more complex than substitution reactions.
Elimination reactions almost always give mixtures of alkene products, and we can usually predict which will be the major product.

60. Substitution and Elimination

61. Dehydrohalogenation Elimination
That is, dehydrohalogenation reaction when alkyl
halide is heated with a strong base using a
relative non-polar solvent.

62. Elimination: Dehydrohalogenation (cont.)
Note that both base and nucleophile are electron rich
species, hence both elimination and nucleophilic reaction
would occur at the same time unless the reaction conditions are carefully chosen.
Normally, elimination reaction
occurs at high temperature, alcoholic medium (relatively
non-polar) and the alkyl halide is highly branched (e.g.
tertiary or secondary).

63. Elimination Reactions
The reactions in which two groups or atoms are removed from molecule are called Elimination reaction. They result in the formation of unsaturated compounds.
Elimination reactions involve the loss of elements from the starting material to form a new  bond in the product.

64. Classification
The two leaving group’s may be removed from the two adjacent atom OR from the same carbon or On this bases elimination reaction are classified as,
1-2 OR β-Elimination
The reaction in which both the groups are removed from two adjacent atoms is called β-elimination or 1-2 elimination reaction. This results in the formation of double bond. The general β-elimination reaction can be represented as

65. 1-1 or α Elimination
The reaction in which elimination of two groups occur from the same carbon. The carbon to which the leaving group is attached is called α carbon. As the elimination only occurs from α carbon. Therefore the reaction is called α elimination and a carbene is formed.
carbene

66. E2 Mechanism
In E2 Mechanism both the groups get deposit simultaneously. Thus the rate of the reaction depends on both the concentration of substrate and base.

67. ORIENTATION IN E2 MECHANISM
There are some substrates on which more than one β carbon are available e.g. Let us consider the alkyl halide
Here in this case two β carbon are available so if base induced elimination of this molecule is taken in to consideration then two kinds of olefin will be possible so in this case we consider elimination reaction to be in two modes.

68. Hoffman Elimination
The elimination gives olefin carrying less number of alkyl groups. In this case the hydrogen is eliminated from that β carbon that carries maximum number of hydrogen atoms.
Zaitsev Elimination (Zaitsev’s rule)
The elimination gives olefin carrying greater number of alkyl group. In this case the hydrogen is eliminated from that β carbon that carries minimum number of hydrogen atoms.

69. (Zaitsev’s rule)

70. E1 Mechanism
It is a two steps process in the first step the substrate ionizes to form carbonium ion by losing the leaving group. In the second step, the carbonium ion loses hydrogen from the β carbon to from the product.

71. THREE POSSIBAL REACTIONS
II)
III)

72. E1cB Mechanism
We know that in E1 mechanism X leaves first and then hydrogen, In E2 mechanism X and H Leave simultaneously.
There is a 3rd possibility that H leaving 1st and then X. This is called E1cB mechanism.

73. E1cB Mechanism
Therefore in E1cB mechanism H leaves first leading to the
formation of carbanion (─ ive charge).
The carbanion loss X to form the end products. This reaction is therefore completed in two steps. This mechanism is called cabanion mechanism.