Organic Chemistry

ELEVENTH EDITION

Solomons • Fryhle • Snyder

Chapter 11

Alcohols and Ethers

Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Only used to avoid carbocation rearrangements

Need to use Hg(OAc) 2 to make this work without rearrangement

H 2 O and ROH order reversed for R = CH 3

HO – and RO – order reversed for R = CH 3

Secondary carbocation rearranges before bromide adds

Turning OH into a Leaving Group Without C

+

Rearrangements

• Thionyl chloride replaces Cl for OH without carbocation rearrangements • Mechanism ultimately involves S N 2 reaction, so inversion of configuration results • Can also use PCl 3 to achieve the same result

• Phosphorus tribromide replaces Br for OH without carbocation rearrangements • Mechanism ultimately involves S N 2 reaction, so inversion of configuration results • Can also use thionyl bromide to achieve same result

• Alkanesulfonyl chlorides turn OH groups into leaving groups which can be replaced by ANY nucleophile (not just Br or Cl) • No carbocations are involved; no rearrangements occur • Ultimate substitution involves S N 2 reaction so inversion stereochemistry results

• If necessary mercury can be used to add ROH across a double bond without carbocation rearrangements.

• If double bond is not symmetric, pseudopolarize it and polarize the alcohol with H(+) and RO(-) to figure out the correct product

• TBS will replace H of an alcohol to act as a protecting group for the alcohol • Polarize H(+) and RO(-) in the alcohol and TBS(+) and Cl(-) in TBSCl • Si loves F even more than O and will grab F – break off the TBS protecting group and spit out RO – when you need to

Regeneration of the original alcohol by breaking off the TBS protecting group after doing some chemical reactions on the R group

• Normally only HBr, HI, and H 2 SO 4 are acidic enough to cleave ethers • In this case, however, the stability of tertiary carbocation which results from H – shifting and substituting for CH 3 OH makes this reaction work with HCl • If tertiary carbocations can be formed then HCl is strong enough to cleave ethers

• In acid the nucleophile attacks the carbon which would support the most stable carbocation (unconventional S N 2 reaction - driven by charge on C rather than steric accessibility) • This carbon only develops a partial + charge; remains bonded to O until this bond broken by nucleophile • Therefore no carbocation rearrangements occur (O bridge prevents them like in Hg case) • Also product has nucleophile and OH group oriented as if they did an ANTI addition to a double bond (like in Br 2 or Cl 2 addition to a double bond)

• In base the nucleophile attacks the less hindered carbon (conventional S N 2) • Orientation of nucleophile and OH are low symmetry like in acid case

• For product analysis polarize the less hindered C(+) and the epoxide O(–) • Polarize the nucleophile in the normal manner, break the correct C-O epoxide bond, and add the + fragment from the nucleophile to the – epoxide O; add the – fragment from the nucleophile to the + carbon of the epoxide ring

• Under acidic conditions the C which supports the most + charge gets the + polarization • Polarize everything else in the usual fashion and swap partners as usual with polar reactions • The correct bond to break in the epoxide is the one which connects the negatively polarized O to the carbon which you polarized positive

• In this case the products are low-symmetry • Because the three groups on one chiral carbon are the same as the three groups on the other chiral carbon the high-symmetry product would be meso • Since the reactant is high-symmetry (cis) and the reaction produces the same product as a low-symmetry (anti) addition to a double bond the product symmetry is low

In this case a low-symmetry reactant (trans) multiplied by a low-symmetry reaction (effective anti addition) calculates a high-symmetry product (meso)

• In these cases the actual calculation goes as follows: • Start with a high- or low-symmetry alkene (+ or -) • Multiply by a high-symmetry reaction (+) to make the cis epoxide • Multiply by a low-symmetry reaction (S N 2 inversion, – symmetry) to make the final product

Crown Ethers

Make ionic compounds soluble in nonpolar solvents and make anionic nucleophiles very reactive