1. Unit 4 Nomenclature and Properties of Alkyl Halides Synthesis of Alkyl Halides Reactions of Alkyl Halides Mechanisms of S N 1, S N 2, E1, and E2 Reactions Substrate, Nucleophilicity, and Leaving Group Effects

2. Alkyl Halides Alkyl halide: a compound with a halogen atom bonded to one of the sp 3 hybrid carbon atoms of an alkyl group Two types of names: IUPAC system Common names

3. Nomenclature IUPAC System: Alkyl halides are named as an alkane with a halo-substituent: Review the rules for naming alkanes covered in Unit 2 1-chloropropanebromocyclohexane

4. Nomenclature Common Names: alkyl group name + halide n-propyl chlorideCyclohexyl bromide

5. Nomenclature Special common names: CH 2 X 2 = methylene halide CHX 3 = haloform CX 4 = carbon tetrahalide CH 2 Cl 2 CHCl 3 CCl 4 chloroform trichloromethane Methylene chloride dichloromethane Carbon tetrachloride tetrachloromethane

6. Types of Alkyl Halides Alkyl halides can be classified by the type of carbon atom the halogen is bonded to: primary halide (1 o ): halogen attached to a 1 o carbon secondary halide (2 o ): halogen attached to a 2 o carbon tertiary halide (3 o ): halogen attached to a 3 o carbon

7. Types of Alkyl Halides Geminal dihalide: 2 halogens bonded to the same carbon atom Vicinal dihalide: 2 halogens bonded to adjacent carbon atoms

8. Other Organic Halides Aryl halide: halogen is attached directly to an aromatic ring Benzylic halide halogen is attached to a carbon that is attached to a benzene ring thyroxine benzylic carbon benzylic chloride

9. Other Organic Halides Allylic halide: halogen is attached to a carbon that is attached to a C=C Allylic carbon Allylic chloride

10. Other Organic Halides Vinyl Halide: halogen attached to a carbon that is part of a C=C Monomer for PVC Monomer for teflon

11. Uses of Alkyl Halides Anesthetics: Chloroform (CHCl 3 ) toxic carcinogenic (causes cancer) Solvents: CCl 4 formerly used in dry cleaning CH 2 Cl 2 formerly used to decaffeinate coffee liquid CO 2 used now

12. Uses of Alkyl Halides Freons: Freon-12: CF 2 Cl 2 Freon-22: CHClF 2 Freon-134a: Pesticides: DDT Chlordane (termites)

13. Physical Properties Boiling Point: Compounds with higher MW’s and greater surface area (more linear) tend to have higher BP. BP increases as size of halogen increases F < Cl < Br < I BP decreases as branching increases

14. Physical Properties Density: Alkyl chlorides are common solvents for organic reactions. CH 2 Cl 2 CHCl 3 CCl 4 More dense than water

15. Preparation of Alkyl Halides Alkyl halides can be prepared from a variety of starting materials including alkanes, alkenes, alkynes, alcohols, and other alkyl halides. You are responsible for knowing and applying the synthesis of R-X by: free radical halogenation reactions free radical allylic bromination reactions

16. Preparation of Alkyl Halides Free Radical Halogenation of Alkanes alkane + X 2 alkyl halide(s) + HX Limited utility due to generally poor selectivity and yield. Useful when only one type of reactive hydrogen is present Bromination is more selective and gives the product formed from the most stable free radical. h  or 

17. Preparation of Alkyl Halides Useful Examples: hh hh 50 % 90 %

18. Preparation of Alkyl Halides Free Radical Allylic Bromination: where NBS = N-bromosuccinimide hh NBS

19. Preparation of Alkyl Halides Allylic bromination more selective allylic free radical is resonance stabilized Addition of Br 2 to the double bond is a competing reaction use low levels of Br 2 by generating it “in situ” using NBS

20. Preparation of Alkyl Halides Examples: hh hh

21. Reactions of RX Most reactions of alkyl halides involve breaking the C-X bond. Nucleophilic substitution Elimination The halogen serves as a leaving group in these reactions: nucleophile can attack the carbon bearing the  + the halogen can leave as X -, taking the bonding electrons with it ++ --

22. Reactions of RX Nucleophilic substitution: reaction in which a nucleophile replaces a leaving group Nucleophile: electron pair donor Leaving group: an atom or group of atoms that are lost during a substitution or elimination reaction retains both electrons from the original bond

23. Reactions of RX General Equation for Nucleophilic Substitution Example: - + Br - - -

24. Reactions of RX Elimination Reaction: two substituents are lost from adjacent (usually) carbons, forming a new  bond Dehydrohalogenation: an elimination reaction in which H + and X - are lost, forming an alkene CH 3 O -

25. Reactions of RX There are two common types of nucleophilic substitution reactions: S N 1 reactions substitution, nucleophilic, unimolecular 3 o, allylic, benzylic halides weak nucleophiles S N 2 reactions substitution, nucleophilic, bimolecular methyl and 1 o halides strong nucleophiles

26. Reactions of RX

27. Common strong nucleophiles: hydroxide ion alkoxide ions many amines iodide and bromide ions cyanide ion Common weak nucleophiles: water alcohols fluoride ion

28. S N 2 Reactions The reaction between methyl iodide and hydroxide ion is a concerted reaction that takes places via an S N 2 mechanism - - nucleophile substrate product Leaving group Substrate: the compound attacked by a reagent (nucleophile)

29. S N 2 Reactions Concerted reaction: a reaction that takes place in a single step with bonds breaking and forming simultaneously S N 2: substitution, nucleophilic, bimolecular transition state of rate-determining step involves collision of 2 molecules 2nd order overall rate law Rate = k[RX][Nuc]

30. S N 2 Reactions S N 2 Mechanism: Nucleophile attacks the back side of the electrophilic carbon, donating an e - pair to form a new bond Since carbon can only have 8 valence electrons, the C-X bond begins to break as the C-Nuc bond begins to form -- -

31. S N 2 Reactions S N 2 Mechanism for the reaction of methyl iodide and hydroxide ion: - - + I -

32. S N 2 Reactions Reaction Energy Diagram: large E a due to 5-coordinate carbon atom in transition state no intermediates exothermic

33. S N 2 Reactions S N 2 reactions occur with inversion of configuration at the electrophilic carbon. The nucleophile attacks from the back side (the side opposite the leaving group). Back-side attack turns the tetrahedron of the carbon atom inside out.

34. S N 2 Reactions Inversion of configuration: a process in which the groups bonded to a chiral carbon are changed to the opposite spatial configuration: R S or S R

35. S N 2 Reactions Example: Predict the product formed by the S N 2 reaction between (S)-2-bromobutane and hydroxide ion. Draw the mechanism for the reaction.

36. S N 2 Reactions The S N 2 displacement reaction is a stereospecific reaction a reaction in which a specific stereoisomer reacts to give a specific diastereomer of the product + OH - + Br -

37. S N 2 Reactions S N 2 reactions occur under the following conditions Nucleophile: strong, unhindered nucleophile OH - not H 2 O CH 3 O - not CH 3 OH CH 3 CH 2 O - not (CH 3 ) 3 CO - Substrate: 1 o or methyl alkyl halide (most favored) 2 o alkyl halide (sometimes) 3 o alkyl halides NEVER react via S N 2

38. S N 2 Reactions The relative rate of reactivity of simple alkyl halides in S N 2 reactions is: methyl > 1 o > 2 o >>>3 o 3 o alkyl halides do not react at all via an SN2 mechanism due to steric hinderance. The back side of the electrophilic carbon becomes increasingly hindered as the number or size of its substituents increases

39. S N 2 Reactions Steric hinderance at the electrophilic carbon:

40. S N 2 Reactions S N 2 reactions can be used to convert alkyl halides to other functional groups: RX + I - R-I RX + OH - R-OH RX + R’O - R-OR’ RX + NH 3 R-NH 3 + X - RX + xs NH 3 R-NH 2 RX + CN - R-CN RX + HS - R-SH RX + R’S - R-SR’ RX + R’COO - R’CO 2 R KNOW THESE! Be able to apply these!

41. S N 2 Reactions Example: Predict the product of the following reactions:

42. S N 2 Reactions Example: What reagent would you use to do the following reactions: ? ?