1 (226)

Prévia do material em texto

180 Chapter 9 FURTHER REACTIONS OF ALCOHOLS AND THE CHEMISTRY OF ETHERS 51. The problem requests that we figure out how to carry out the following change: CH₂CH₂CH₂OH turn and into OH We begin by identifying in detail exactly what we are being asked to do: (1) make a new carbon-carbon bond. (2) change a ketone into a tertiary alcohol. and (3) get rid of a carbon-halogen bond in the process. At this stage we don't have a lot of carbon-carbon bond-forming reactions to choose from, and we can settle on some form of addition of an organometallic reagent. derived from the brominated compound. to the ketone carbonyl carbon atom (Section 8-8). For the organometallic a Grignard reagent of the struc- ture comes to mind. But we recall (Sections 8-7 and 8-9, and see also Problem 42 in Chapter 8) that alcohol functions and Grignards are incompatible with one another, because the acidity of the 0-H group is enough to destroy a C-Mg or C-Li bond by protonation of the carbon atom (which is strongly basic in this type of compound) in a very favorable acid-base M⁻. To do this synthesis. therefore. we cannot have the bond present during the formation or use of the organometallic species. The chemistry we have seen in Chapter 9 (Section 9-8 in particular) gives us ways to solve this problem. Ethers are unreactive toward organometallics. and tertiary ethers can be readily formed from alcohols and. later. hydrolyzed by acid to give back alcohols. They make good protecting groups for alcohols in situations such as this. Our solution. therefore. is to begin by converting the -OH group of the 3-bromopropanol into a tertiary ether: The -OH function is gone and we can proceed with the Grignard process: CH₂CH₂CH₂OC(CH₃)₃ CH₂CH₂CH₂OH OH Notice that the aqueous acid necessary in the Grignard synthesis to protonate the initially formed alkoxide and convert it into the target tertiary alcohol. is also sufficient to hydrolyze the tertiary ether protecting group. releasing the primary alcohol at the end of the three-carbon chain. 52. The leaving group in a hypothetical nucleophilic displacement reaction to cleave any acyclic ether would be an alkoxide. Alkoxides are strong bases. Strong bases are poor leaving groups. Nuc:- Poor leaving group The exception is the SN2 displacement reaction to cleave an oxacyclopropane. The release of bond-angle strain upon opening the three-membered ring overcomes the unfavorable energetics associated with producing a poor leaving group. 53. (a) Ethyloxacyclopropane (racemic): (b) (c) (2R.5S)-2-(chloromethyl)- 5-methoxyoxacyclopentane [common name: (d) 4-oxacy- clohexanol: (e) oxacycloheptane: (f) 2.2-dimethyl-1.3-dioxacycloheptane.