1. Alkyl Halides Preparation and Reactions
ORGANIC CHEMISTRY- 1
Alkyl Halides Preparation and Reactions BY
Dr. Ghulam Abbas
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. Halogens increase in size going down the periodic table, so the lengths of carbon–halogen bonds increase accordingly. In addition, C -X bond strengths decrease going down the periodic table.
Such as for CH3F bond length 139 pm and bond strength is 460 kJ/mol while CH3Br bond length is 178 pm and bond strength 294 kJ/mol.

4. Nomenclature

5. 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”.

6. There are other types of organic 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).

7. Preparation
1. Halogenation

9. Preparation
Reaction with HX
HX is obtained from NaX + conc. H2SO4

10. Preparation
From alcohol 3 3

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

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

13. 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.

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

15. Chemical Properties
Hydrolysis – For phenol – industrial process

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

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

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

19. Chemical Properties
Formation of nitrile

20. Chemical Properties Formation of ether (Williamson’s synthesis)
But not:
(Why?)
RX is usually 1ry
alkyl halide should
NOT be 2ry and 3ry.
(Why?)

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

22. Chemical properties
Formation of Grignard Reagent
excess

23. Chemical properties
Wurtz Reaction
Wurtz – Fittig Reaction

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

25. Chemical Properties
Reduction

26. 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

27. 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.

28. 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.

29. 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)

30. Chemical Properties -
Transition state

31. 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.

32. 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

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

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

35. 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.

36. 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.

37. 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.

38. 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.

39. 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.

40. The SN1 Mechanism
carbocation

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. Chemical Properties
intermediate

43. 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.

44. SN1 Reaction Racemization

45. Chemical Properties
Stability of carbonium ion:
 SN SN2

46. Factors affecting choice of mechanism
Structure of alkyl halide
3ry ry ry CH3
SN SN2
Use of 3ry alkyl halide favour SN1 since:
Alkyl group is electron-donating which helps
to stablilise the carbonium ion, thus lower the EA.

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

55. Chemical Properties Effect of halogen:
Since the electronagativity of halogen decreased down the group, C-Cl bond is more polar than the others. Hence, the carbon join to Cl is the most electron deficient, so the carbon in R-Cl in most susceptible to the attack of nucleophile.
The bond strength is also important in determining the rate since bond strength decreased rapidly from C-Cl to C-I bond, the reaction rate decreases in the order :
R – I > R – Br > R – Cl