--KEY--Chemistry 108B Exam# 1-Winter 2015--KEY-After recovering from your Ketones 'R' Us disaster, you reorganize as Sniffin' Ethers,

Inc. Your first task is to synthesize

O18-radiolabelled methoxy-(1-methylcyclohexyl) ether from O18 radiolabelled 1-methyl- cyclohexanol. You propose
two syntheses; create a stepwise mechanism for each pathway and use your mechanisms as part of your
explanation of which, if either, of your proposed syntheses will work. If a synthesis WON'T work, use your mechanism
to show what product WILL form and explain WHY the synthesis won't work. Pay attention to the O18!

A frighteningly large majority of you not only completely IGNORED the whole point of the
question, which was CAN YOU PUT THE RADIOLABELLED 18O where the problem requires it
to be, but did not even mention the 18O in any part of your answer: PLEASE READ
CAREFULLY!!
18O

H
H C

H(+)

H3C

: :

: :

H3C

OH , H(+)

OCH3

H3C

18OH

H3C

- H218O

- H(+)
H

18OH

H
H C

- H218O

: :

H3C

H3C

OH

H3C

CH3

Great mechanism, Gar', except that you LOST your 18O radio label1 There is NO way to
synthesize the radiolabelled ether with the 18O still attached to the cyclohexane ring using an
acid-catalyzed SN1 reaction. Thus, the ether formed is the unlabelled analog of the desired
product....and, yes, I expect you to remember from 108A that the reaction conditions
overwhelmingly favor an SN1 pathway over an SN1 pathway.
18O

(1) NaH

:H(-)

H
(2) H C
H

: :

: :

H3C

I:

H3C 18OCH3

10 = Mechs 3@; Expl 2@

H
18O :

: :

: :

H3C

I:

H3C

18OCH

An even greater mechanism because it works!! Deprotonation of the ROH with the powerful
base NaH (pKa of H2 = 35) creates the highly nucleophilic R18O(-) AND preserves the 18O radio
label on the ring. The subsequent SN2 reaction with Iodomethane gives the desired ether with no
E2 side-products and NO loss of the 18O radio label. Oh, and by the way, the two additional
neutrons in the nucleus of the 18O contribute absolutely NOTHING to the size of the 18O; if you
made this mistake, then you'd better review your Chem 1C nuclear chemistry notes and your
Chem 1A notes about the size of the nucleus vs. the overall size of an atom.