Download Mon Feb 15 lecture

Lecture outline
4. Friedel-Crafts reactions —
a. Alkylation
+
R
AlCl3
R–Cl
(+ HCl)
(catalyst)
(R = methyl, 1°, 2°, 3°;
R ≠ vinyl, aryl)
After initial complexation with the Lewis acid catalyst,... (add the charges!)
R—Cl
+
AlCl3
R—Cl—AlCl3
— 2° and 3° alkyl halides react via an SN1-type mechanism
(i.e. via 2° or 3° carbocation):
(add the lone pairs, charges, and curved arrows!!!)
H
R—Cl—AlCl3
– AlCl4 –
H
R
R
1. loss of
leaving group
2. addition of
nucleophile
etc
Cl—AlCl3
R
(+ HCl
+ AlCl3 )
— methyl and 1° alkyl halides react via an SN2-type mechanism
(i.e. direct displacement):
H
+
R—Cl—AlCl3
– AlCl4 –
H
R
etc
keep in mind that carbocations sometimes rearrange...
not
Cl
+
AlCl3
write the mechanism:
...and rearrangements are sometimes observed even with 1° halides —
in these cases, a hydride or alkyl shift is concerted with loss of the l.g.,
— this pathway avoids the intermediacy of a high-E 1° cation.
(This is frequently observed in carbocation chemistry; we've already seen a
similar concerted rearrangement and leaving group (water)
departure in the reaction of some 1° alcohols with strong acid.)
not
Cl
+
AlCl3
Add the curved arrows to show the concerted H shift and loss of the leaving group.
H
– AlCl4 –
Cl
AlCl3
CH3
usual EAS mech
H
CH2
How are the 2-step (via the 1° cation) and 1-step routes analogous to SN1 and SN2
mechanisms, respectively? What functions as the "nucleophile" in the concerted pathway?
Note that the reactions shown on p 692 of the text likely involve a competition between
SN2 mechanism to attach the 1° C directly to the aromatic ring and a concerted rearrangement
similar to the one shown above to produce a 2° (or 3°) cation directly. There is no compelling
experimental evidence that localized 1° cations are ever formed under these conditions.
The mechanism in the study guide for problem 17.14 (benzene + 1-chloropropane +
AlCl3 —> propylbenzene + isopropyl benzene) is almost certainly wrong. Let's write a more
reasonable mechanism for each pathway
— 2° and 3° cations can also be generated in other ways — what reagents might we use to
convert isobutylene and t-butyl alcohol to t-Bu cation? ...
EAS
OH
b. Acylation
+
R
O
AlCl3
C
(catalyst)
Cl
(an acyl chloride)
O
C
R
(+ HCl)
Complete the mechanism below by adding charges, lone pairs, and curvy arrows. Loss of the
leaving group generates an acylium ion, which is resonance stabilized, and thus has no tendency
to rearrange. Show both resonance structures, then show this cation attaching to benzene via the
usual EAS mechanism.
O
R
C
+
Cl
R
O
R
O
AlCl3
C
C
– AlCl4 –
Cl
AlCl3
AlCl3
Cl
dead end
Friedel-Crafts acylation provides a way to avoid rearrangements that often accompany FC alkylation. For example, benzene cannot be converted to isobutyl benzene directly by rxn
with iBu–Cl with AlCl3 (direct route below; another product is formed instead — what is it and
how is it formed? Hint: you just saw this 2 pages back!)
Cl
AlCl3
AlCl3
Cl
O
O
Zn(Hg), aq HCl
or
H2NNH2, HO –, H2O, !
This can be avoided by (see the lower 2-step route) F–C acylation followed by either (a)
Clemmensen reduction (zinc-amalgam and aqueous acid) or (b) Wolff-Kishner reduction
(hydrazine, base, protic solvent, and lots of heat) avoids the rearrangement problem. (We’ll
learn a bit more about these when we get to carbonyl chemistry.)
— F-C acylation is quite a general procedure; a variety of different acyl groups can be
introduced by this method. Here an a couple of other examples — draw the products formed
from the following reactions:
benzene
+
AlCl3
PhCOCl
O
AlCl3
Cl
5. H+ (D+) as the electrophile —
D
D
+
D2O (excess)
C6H6
D
D
D
D
D
C6D6
(an NMR solvent)
(desulfonation is another example of this — in that case, an H+ adds and an
SO3H+ is later lost)