9 Alcohols, Ethers, and Epoxides 9.1 Introduction 9.2 Structure and bonding 9.3 Nomenclature 9.4 Physical properties 9.5 Interesting alcohols, ethers, and epoxides 9.6 Preparation of alcohols, ethers, and epoxides 9.7 General features— Reactions of alcohols, ethers, and epoxides 9.8 Dehydration of alcohols to alkenes 9.9 Carbocation rearrangements 9.10 Dehydration using POCl3 and pyridine 9.11 Conversion of alcohols to alkyl halides with HX 9.12 Conversion of alcohols to alkyl halides with SOCl2 and PBr3 9.13 Tosylate—Another good leaving group 9.14 Reaction of ethers with strong acid 9.15 Reactions of epoxides 9.16 Application: Epoxides, leukotrienes, and asthma 9.17 Application: Benzo[a]pyrene, epoxides, and cancer Palytoxin (C129H223N3O54), fi rst isolated from marine soft corals of the genus Palythoa, is a potent poison that contains several hydroxy (OH) groups. Historically used by ancient Hawai- ians to poison their spears, palytoxin was isolated in 1971 at the University of Hawai‘i at Ma–noa, and its structure determined simultaneously by two different research groups in 1981. Its many functional groups and stereogenic centers made it a formidable synthetic target, but in 1994, Harvard chemists synthesized palytoxin in the laboratory. In Chapter 9 we learn about the properties of alcohols like palytoxin, as well as related oxygen-containing functional groups. 312 smi75625_312-357ch09.indd 312 10/27/09 3:03:44 PM 9.1 Introduction 313 In Chapter 9, we take the principles learned in Chapters 7 and 8 about leaving groups, nucleo- philes, and bases, and apply them to alcohols, ethers, and epoxides, three new functional groups that contain polar C – O bonds. In the process, you will discover that all of the reactions in Chap- ter 9 follow one of the four mechanisms introduced in Chapters 7 and 8—SN1, SN2, E1, or E2— so there are no new general mechanisms to learn. Although alcohols, ethers, and epoxides share many characteristics, each functional group has its own distinct reactivity, making each unique and different from the alkyl halides studied in Chapters 7 and 8. Appreciate the similarities but pay attention to the differences. 9.1 Introduction Alcohols, ethers, and epoxides are three functional groups that contain carbon–oxygen σ bonds. O ROH ROR alcohol ether epoxide Alcohols contain a hydroxy group (OH group) bonded to an sp3 hybridized carbon atom. Alco- hols are classifi ed as primary (1°), secondary (2°), or tertiary (3°) based on the number of carbon atoms bonded to the carbon with the OH group. Alcohol Classification of alcohols H R R COH hydroxy R C OH R C OH R C OH group H H R ° ° ° sp3 hybridized C 1 2 3 (one R group) (two R groups) (three R groups) Compounds having a hydroxy group on an sp2 hybridized carbon atom—enols and phenols— undergo different reactions than alcohols and are discussed in Chapters 11 and 19, respectively. Enols have an OH group on a carbon of a C – C double bond. Phenols have an OH group on a benzene ring. sp 2 hybridized C OH OH enol phenol Ethers have two alkyl groups bonded to an oxygen atom. An ether is symmetrical if the two alkyl groups are the same, and unsymmetrical if they are different. Both alcohols and ethers are organic derivatives of H2O, formed by replacing one or both of the hydrogens on the oxygen atom by R groups, respectively. Ether CH3CH2 O CH2CH3 CH3 O CH2CH3 symmetrical ether unsymmetrical ether ROR R groups are the same. R groups are different. Epoxides are ethers having the oxygen atom in a three-membered ring. Epoxides are also called oxiranes. O epoxide or oxirane Problem 9.1 Draw all constitutional isomers having molecular formula C4H10O. Classify each compound as a 1°, 2°, or 3° alcohol, or a symmetrical or unsymmetrical ether. smi75625_312-357ch09.indd 313 10/27/09 3:03:46 PM 314 Chapter 9 Alcohols, Ethers, and Epoxides Figure 9.1 δ– δ– δ– Electrostatic potential maps δ+ δ+ δ+ δ+ for a simple alcohol, ether, and epoxide δ+ δ+ O CH OH CH OCH CC 3 3 3 H H H H • Electron-rich regions are shown by the red around the O atoms. Problem 9.2 Classify each OH group in cortisol as 1°, 2°, or 3°. Cortisol is a hormone produced by the adrenal gland that increases blood pressure and blood glucose levels, and acts as an anti-infl ammatory agent. O OH HO OH H H H O cortisol 9.2 Structure and Bonding Alcohols, ethers, and epoxides each contain an oxygen atom surrounded by two atoms and two nonbonded electron pairs, making the O atom tetrahedral and sp3 hybridized. Because only two of the four groups around O are atoms, alcohols and ethers have a bent shape like H2O. sp3 hybridized sp3 hybridized O ==O CH3 H CH3 CH3 109° 111° The bond angle around the O atom in an alcohol or ether is similar to the tetrahedral bond angle of 109.5°. In contrast, the C – O – C bond angle of an epoxide must be 60°, a considerable devia- tion from the tetrahedral bond angle. For this reason, epoxides have angle strain, making them much more reactive than other ethers. 60° O = H H HH a strained, three-membered ring Because oxygen is much more electronegative than carbon or hydrogen, the C – O and O – H bonds are all polar, with the O atom electron rich and the C and H atoms electron poor. The elec- trostatic potential maps in Figure 9.1 show these polar bonds for all three functional groups. 9.3 Nomenclature To name an alcohol, ether, or epoxide using the IUPAC system, we must learn how to name the functional group either as a substituent or by using a suffi x added to the parent name. 9.3A Naming Alcohols In the IUPAC system, alcohols are identifi ed by the suffi x -ol. smi75625_312-357ch09.indd 314 10/27/09 3:03:46 PM 9.3 Nomenclature 315 HOW TO Name an Alcohol Using the IUPAC System Example Give the IUPAC name of the following alcohol: CH3 OH CH3CHCH2CHCH2CH3 Step [1] Find the longest carbon chain containing the carbon bonded to the OH group. CH3 OH CH3CHCH2CHCH2CH3 • Change the -e ending of the parent alkane to the -ol. 6 C's in the longest chain suffi x 6 C's hexane hexanol Step [2] Number the carbon chain to give the OH group the lower number, and apply all other rules of nomenclature. a. Number the chain. b. Name and number the substituents. methyl at C5 CH3 OH CH3CHCH2CHCH2CH3 CH3 OH CH3CHCH2CHCH2CH3 6 54321 • Number the chain to put the 5 3 OH group at C3, not C4. Answer: 5-methyl-3-hexanol 3-hexanol When an OH group is bonded to a ring, the ring is numbered beginning with the OH group. CH3CH2CH2CH2OH is named Because the functional group is always at C1, the “1” is usually omitted from the name. The ring as 1-butanol using the 1979 is then numbered in a clockwise or counterclockwise fashion to give the next substituent the IUPAC recommendations and butan-1-ol using the 1993 lower number. Representative examples are given in Figure 9.2. IUPAC recommendations. The Common names are often used for simple alcohols. To assign a common name: fi rst convention is more widely used, so we follow it in this • Name all the carbon atoms of the molecule as a single alkyl group. text. • Add the word alcohol, separating the words with a space. H CH3 C OH alcohol isopropyl alcohol CH3 a common name isopropyl group Compounds with two hydroxy groups are called diols (using the IUPAC system) or glycols. Com- pounds with three hydroxy groups are called triols, and so forth. To name a diol, for example, the suffi x -diol is added to the name of the parent alkane, and numbers are used in the prefi x to indicate the location of the two OH groups. Figure 9.2 C2 CH3 Examples: Naming CH3 OH OH cyclic alcohols C3 C1 C1 CH3 CH3 3-methylcyclohexanol 2,5,5-trimethylcyclohexanol The OH group is at C1; the second substituent The OH group is at C1; the second substituent (CH3) gets the lower number. (CH3) gets the lower number. smi75625_312-357ch09.indd 315 10/27/09 3:03:47 PM 316 Chapter 9 Alcohols, Ethers, and Epoxides C1 H HO HOCH CH OH HOCH C CH OH C2 2 2 2 2 two OH groups OH ethylene glycol HO (1,2-ethanediol) glycerol trans-1,2-cyclopentanediol (1,2,3-propanetriol) Common names are usually used Numbers are needed to show for these simple compounds. the location of two OH groups. Problem 9.3 Give the IUPAC name for each compound. CH3 a. OH b. c. OH OH Problem 9.4 Give the structure corresponding to each name. a. 7,7-dimethyl-4-octanol c. 2-tert-butyl-3-methylcyclohexanol b. 5-methyl-4-propyl-3-heptanol d. trans-1,2-cyclohexanediol 9.3B Naming Ethers Simple ethers are usually assigned common names. To do so, name both alkyl groups bonded to the oxygen, arrange these names alphabetically, and add the word ether. For symmetrical ethers, name the alkyl group and add the prefi x di-. H CH3 OCCH2CH3 CH3CH2 OCH2CH3 CH methyl 3 ethyl ethyl sec-butyl diethyl ether sec-butyl methyl ether Alphabetize the b of butyl before the m of methyl. More complex ethers are named using the IUPAC system. One alkyl group is named as a hydro- carbon chain, and the other is named as part of a substituent bonded to that chain.