Epoxides (Functional Group)

Epoxides - nomenclature, chemical reactions, physical and chemical properties, mechanisms

1. University of Guyana Division of Natural Sciences ORGANIC CHEMISTRY ( CHM 2201) EPOXIDES LECTURER: …………….. GROUP MEMBERS ………………………………..

2. OBJECTIVES Definition Structure Physical Properties Nomenclature Reactivity Preparation

3. DEFINITION An epoxide  is a cyclic ether with a three-atom ring (heterocyclic system). This ring is similar to an equilateral triangle, which makes it strained (unstable), and hence highly reactive, more so than other ethers. 

4. STRUCTURE

5. PHYSICAL PROPERTIES Similar to analogous ethers Low molecular weight Colourless Nonpolar Often volatile

6. NOMENCLATURE There are two methods for naming epoxides Alkene oxide style (As the oxide of the corresponding alkene) The root name is for the corresponding alkene (think of removing the oxygen and adding a C=C at that location). Add the suffix oxide.  This is common for very simple epoxides .

7. Epoxy style (Using the prefix epoxy- to indicate the epoxide as a substituent) The root name is based on the longest chain with the two C-O bonds attached. The chain is numbered so as to give the epoxide unit the lowest possible locant (again like alkenes ) The epoxide prefix is inserted prior to the root name along with both locants e.g. 1,2-epoxypropane. Both locants are included since this method is also used for naming other cyclic ethers.

8. Examples Alkene oxide style : Functional group is an epoxide, therefore suffix = - ene oxide The longest continuous chain is C3 therefore root = prop Location of "alkene" is unambiguous, so no locant needed. propene oxide

9. Examples Epoxy style : The longest continuous chain is C3 therefore root = prop The epoxide is a substituent therefore prefix = epoxy Number to give epoxide (only group present) the lowest locants = 1,2- 1,2-epoxypropane

10. Examples Alkene oxide style : Functional group is an epoxide, therefore suffix = - ene oxide The longest continuous chain is C6 therefore root = hex The system is cyclic therefore prefix = cyclo Location of "alkene" is unambiguous, so no locant needed. cyclohexene oxide

11. Examples Epoxy style : The longest continuous chain is C6 therefore root = hex The root system is cyclic therefore prefix = cyclo The epoxide is a substituent therefore prefix = epoxy Number to give epoxide (only group present) the lowest locants = 1,2- 1,2-epoxycyclohexane

12. Examples Alkene oxide style : Functional group is an epoxide, therefore suffix = - ene oxide The longest continuous chain is C3 therefore root = prop There is a C3 halide substituent = chloro The halide group locant = 3- Location of "alkene" is unambiguous, so no locant needed. 3 – chloro propene oxide

13. Examples Epoxy style : The longest continuous chain is C3 therefore root = prop There is a C3 halide substituent = chloro The halide group locant = 3- The epoxide is a substituent therefore prefix = epoxy Number to give epoxide (only group present) the lowest locants = 1,2- 3- chloro-1,2-epoxypropane

14. Examples Alkene oxide style : Functional group is an epoxide, therefore suffix = - ene oxide The longest continuous chain is C6 therefore root = hex There is a C1 alkyl substituent = methyl The first point of difference rule requires numbering from the right as drawn to make the "alkene" locant = 2- Hence the methyl group locant = 5- 5-methyl-2-hexene oxide

15. Examples Epoxy style : The longest continuous chain is C6 therefore root = hex There is a C1 alkyl substituent = methyl The first point of difference rule requires numbering from the right as drawn The epoxide is a substituent therefore prefix = epoxy Number to give epoxide (only group present) the lowest locants = 2,3- 2,3-epoxy-5-methylhexane

16. REACTIVITY Epoxides are significantly more reactive than simple ethers. The small ring system has high ring strain that can be relieved by opening the ring. Nucleophiles attack the C of the C-O bond causing the C-O bond to break, resulting in ring opening.

17. Preparation of epoxides Epoxides are most commonly prepared by either of two ways: Epoxidation of Alkenes Synthesis from halohydrins

18. Epoxidation of alkenes Reaction type: Electrophilic Addition Start at the C=C as the nucleophile , make a bond to the slightly electrophilic O. Break the weak O-O bond and form a C=O . B reak the original C=O to make a new O-H bond. b reak the original O-H to form the new C-O bond

19. General mechanism N.B. epoxidation of alkenes usually produce a carboxylic acid as an end product 1 2 3 4

20. Epoxidation of cyclohexene mechanism +

21. SYNTHESIS FROM HALOHYDRIN Reaction type: Electrophilic Addition then Nucleophilic Substitution Step 1: An acid/base reaction. The base deprotonates the alcohol forming an alkoxide intermediate that has enhanced nucleophilicity . Step 2: An intramolecular S N 2 reaction where the alkoxide nucleophile attacks the electrophilic C displacing the leaving group, the halide ion. The nucleophile has to attack anti to the C-X bond.

22. General mechanism X X X X, H 2 O Na + OH - - H H Formation of halohydrin step 1 3 2 H H H H

23. Synthesis of cyclohexene oxide via halohydrin Cl 2 , H 2 Na + OH - - Acts as the base 1 2 3

24. Reactions involving epoxides The most common reactions involving epoxides are the ring opening reactions. The ring opening reactions of epoxides can take place under basic conditions or acidic conditions

25. Ring opening reactions Acidic conditions epoxides open in a “ sn1 like” fashion The nucleophile will attack the most substituted carbon weak nucleophile required Basic conditions epoxides open in a “ sn2 like” fashion The nucleophile will attack the least substituted carbon Strong nucleophile required

26. acidic conditions (sn1): general mechanism

27. acidic conditions (sn1): example ((1,2 epoxy-1- methyl cyclohexane)) , 1 2 3 Ethanol (CH3CH2OH) is the nucleophile (weak) in this reaction

28. Basic conditions (sn2): general mechanism

29. Basic conditions (sn2): example (1,2 epoxy-1- methyl cyclohexane) - - 1 2 Ethoxide ion (CH3CH2O-) is the nucleophile (strong) in this reaction

30. Basic conditions (sn2): example (USING GRIGNARD REAGENT) - Grignard reagent acting as the nucleophile Carbon is more electronegative than Mg, thus gaining the electrons 1 2

31. Stereochemistry Compound 1 Compound 2 enantiomers R & S CONFIGURATION In terms of cis & trans isomerism These epoxides would fall under trans isomerism, since their bulky groups are on opposite sides, which is also highlighted in the alkene (alternate sides of the double bond)

32. Compound 1 1 2 1 2 Considering C1 Considering C2 R – Configuration S – Configuration X In terms of C2 the lowest priority atom (H) is not in the back, therefore we assign using the normal rules backwards . i.e. 1-2-3 anticlockwise is R and not S R – Configuration 1 3 2 4 1 2 4 3 (R) 1-Chloro-1,2-epoxy-2-methylethane

33. Compound 2 1 2 Considering C1 Considering C2 1 2 1 2 1 2 S – Configuration R – Configuration X S – Configuration In terms of C1 the lowest priority atom (H) is not in the back, therefore we assign configuration using the normal rules backwards. i.e. 1-2-3 clockwise is S and not R 1 2 3 4 1 2 3 4 (S) 1-Chloro-1,2-epoxy-2-methylethane

34. CIS – TRANS ISOMERISM Cis - trans isomerism has to do with the arrangement of the atoms in space. When two like groups are on the same side of the epoxy substituent, it is said to be a cis - isomer, whereas when the two groups are on opposite sides, it is said to be trans isomer.

35. Summary An epoxide is a cyclic ether with a three membered ring Epoxides are commonly named by either of two styles - Alkene oxide style - Epoxy Style Epoxides are most commonly prepared by - Epoxidation of Alkene - Synthesis from halohydrin

36. SUMMARY Due to epoxides being a three membered ring chain and its structure is somewhat of a triangle, it undergoes high ring strain. Due to its high ring strain, epoxides commonly undergo ring opening reactions. Ring opening reactions that epoxides undergo can occur under both basic and acidic conditions depending on the strength of the nucleophile.

37. SUMMARY The structure of epoxides can also be looked at in terms of stereochemistry; R & S configuration, cis -trans isomerism

38. Reference

39. Well that’s not all any questions????