Reactivity of Organic Halides in Nucleophilic Substitution.

1. Reactivity of Organic Halides in Nucleophilic Substitution.

3. Organic Halides R � X is the general formula for organic halides. R = alkyl or aryl; X = F, Cl, Br & I Most of the organic halides are creatures of the laboratory. Only few of them have been isolated from natural products.

4. Organic Halides � Uses Organohalogen compounds are important for several reason: Versatile reagents in organic synthesis. Can be converted into alkenes by dehydrohalogenation. As solvents (CH2Cl2, CHCl3) Insecticides, herbicides, fire retardants. Refrigerants and Polymers.

5. Nucleophilic Substitution Ethyl bromide reacts with hydroxide ion to give ethanol. OH- is the nucleophile. Bromide ion is called leaving group. One covalent bond is broken and one new bond is formed

6. Nucleophilic Substitution Nucleophile is an electron rich species. Nucleophiles can be classified according to the kind of atom that forms a new covalent bond. 1. Oxygen nucleophile (HO-, CH3O- �) 2. Nitrogen nucleophiles (NH3, RNH2�) 3. Sulfur nucleophiles (HS-, RS- �) 4. Halogen nucleophiles (I- �)

7. Nucleophilic Substitution If the nucleophile and substrate are neutral, the product will be positively charged. If the nucleophile is a negative ion and substrate is neutral, the product will be neutral. The unshared pair of electron in the nucleophile can be used to make new covalent bond.

8. Nucleophilic Substitution

9. Nucleophilic Substitution In principle, these reactions may be reversible. Because the leaving group also has an unshared pair of electron and that can be used to make a new covalent bond.

10. Nucleophilic Substitution We use various method to force the reaction to go in forward direction. 1. Stronger nucleophile compared to the leaving group. 2. large excess of one of the reagent 3. Temperature

11. Nucleophilic Substitution There are some limitations: 1. What kind of hybridized carbon it is??? 2. What kind of nucleophile it is???

12. Nucleophilic Substitution

13. Nucleophilic Substitution

14. Nucleophilic Substitution

15. Mechanisms There are two nucleophilic substitution mechanism: SN1 and SN2. They depend on: structure of a nucleophile and alkyl halide; the solvent; the reaction temperature�

16. SN2 Mechanism It�s a one step process. The nucleophile attacks from the back side of C � L bond. Nucleophile and the leaving group partly bonded to the carbon at transition state. Departure of the leaving group.

17. SN2 Mechanism �S & N� stands for Nucleophilic Substitution. 2 indicates the reaction is bimolecular i.e. the nucleophile and the substrate are involved in the key step.

19. Factors influencing Rate of SN2 Reaction Concentration of the nucleophile and concentration of substrate increases the rate.

20. Factors influencing Rate of SN2 Reaction Reaction is fastest when the alkyl halide is primary; intermediate for secondary and slower for tertiary. Because the formation of the transition state is easy for primary compare to tertiary. 1? > 2? > 3?

21. It�s a two step mechanism. Formation of the carbocation is first step and which is slow. Second step is the fast i.e. the combination of carbocation with the nucleophile forms product. SN1 Mechanism

22. SN1 Mechanism �S & N� stands for Nucleophilic Substitution. 1 indicate that only one of the two reactant is involved in the rate determining step i.e. formation of carbocation.

23. SN1 Mechanism

24. Factors influencing Rate of SN1 Reaction Rate of the reaction does not depend on the concentration of the nucleophile. It depends only on the concentration of the substrate.

25. Factors influencing Rate of SN1 Reaction Reaction is fastest when the alkyl group of the substrate is tertiary and intermediate for secondary and slower for primary. Because formed carbocation is more stable in tertiary carbon compared to primary. 3? > 2? > 1?

26. SN1 and SN2 Comparison Polar protic solvents favor SN1 reaction e.g. H2O Polar aprotic solvent favor SN2 reaction e.g. Acetone, DMF, DMSO

27. SN1 and SN2 Comparison If the nucleophile is strong; then SN2 is favored. 1. HO- > HOH 2. HS- > HO- 3. NH3 > H2O > HF

28. SN1 and SN2 Comparison If the carbon bearing the leaving group is stereogenic: 1. SN1 reaction occurs with loss of optical activity (that is, with racemization) 2. SN2 reaction occurs with inversion of configuration.

29. Part 1 - Procedure Label seven small test tubes. Take 0.1 mL (1 ml = 20 drops) or 100 mg of each sample. Quickly add 1 mL of 18 % NaI and note the time. Put a stopper and shake it gently Again note the time of first appearance of any solid.

30. Part 1 - Procedure If there is no solid for 5 min. or more than 5 min. then keep the test tube on a water bath (~ 50 ?) and watch for any reaction. Empty the tubes and rinse it with alcohol.

31. Part 1 - Procedure Label seven small test tubes. Take 0.1 mL (1 ml = 20 drops) or 100 mg of each sample. Quickly add 1 mL of 1 % ethanolic silver nitrate solution and note the time. Put a stopper and shake it gently. Again note the time of first appearance of any solid.

32. Part 1 - Procedure If there is no solid for 5 min. or more than 5 min. then keep the test tube on a water bath (~ 50 ?) and watch for any reaction.

33. Effect of Solvent Take 0.1 mL of 2-chlorobutane in a small test tube Quickly add 1 mL of 1 % silver nitrate in water : alcohol (50:50) mixture, note time. Shake it gently. Note the time of first appearance of solid

34. Results Analyze the results by: 1. Nature of leaving group 2. Structure of the substrate. 3. Unhindered primary Vs hindered primary 4. Simple tertiary Vs Cage like tertiary. 5. Effect of polarity 6. Effect of temperature

35. Molecular Modeling

36. Introduction �HYPERCHEM� is an exceptional molecular modeling program and its well known for its: 1. Quality 2. Flexibilty 3. Easy to use

37. Introduction �HYPERCHEM� provides: 1. 3D visualization. 2. animation. 3. chemical calculations. 4. molecular mechanics. 5. drawing and database capabilities.

38. Part � II Make models of a simple organic compounds. Find its dihedral angle and energy for different conformations.

39. Notes Your test tube should be very, very dry. You do not need to weigh exactly 100 mg or 0.1 mL. One of the halides was prepared by you in the Experiment #7.

40. Criteria of the Lab Note Book Organization and format (see instructions in the lab manual). Table of contents. Pages numbered and dated. Data tables. Corrections. Neatness.