Sintesis de 2-Fenilindol
Sintesis de 2-Fenilindol
Adapted by Modi, Monarch, Perriello, Pohland, and Minard (PSU '92) from A.I. Vogel's Elementary Practical Organic Chemistry, Longman Group Ltd., London (1966).
Revised 4/9/01
Introduction:
Indoles are a very important class of heterocyclic compounds that play a major role in cell
physiology. The parent structure and three examples are:
H
CO2H
N H2
5 4
6 7
N H2
HO
CH3
H
Indole:
the parent heterocycle
H
L-Tryptophan:
an essential amino acid
N
Skatole: H
Responsible for the
unpleasant odor of feces.
H
Serotonin:
a potent vasoconstrictor
Indoles with various substituents in the 2 and 3 position can be synthesized via the Fisher indole
synthesis which involves two steps and utilizes a phenylhydrazine and an aliphatic or aromatic
aldehyde or ketone as starting materials. The synthesis of the 2-phenyl derivative prepared in this
experiment involves the reaction of phenylhydrazine with the ketone acetophenone to produce a
phenylhydrazone as shown in step 1 below. Cyclization with subsequent loss of one of the
nitrogens as ammonia is catalyzed by the addition of a strong acid as shown in step 2.
CH3
+
* N H2
CH3
N
H
O
acetophenone
phenylhydrazine
CH3
* N
N
H
acetophenone
phenylhydrazone
methanesulfonic
N
*
N
H
acetophenone
phenylhydrazone
acid
*
N
N H3
step 1
step 2
H
2-phenylindole
mp 188-189
Various acid catalysts, such as zinc chloride, sulfuric acid, boron trifluoride and polyphosphoric acid
have been used to catalyze the second reaction. However, a group of four Chem 36 honors
students (see citation above) tried methanesulfonic acid and found this to be an easy-to-handle
and quite effective acid catalyst.
Although Emil Fisher reported the discovery of this type of indole synthesis in 1883, it was not until
1943 that Allen and Wilson answered the fascinating mechanistic question: Which nitrogen in the
phenylhydrazone intermediate is spit out as ammonia? This was done by labeling the a nitrogen
of the phenylhydrazine with the stable isotope,15N, then carrying out the reaction and examining
the products for the presence of the 15N isotope. The result is shown above, i.e. the labeled
nitrogen (marked with an *) shows up in the indole product, so it is the b nitrogen that is expelled
as ammonia.
Date, Name, Desk #, Experiment # & Title(abbreviated after 1st pg), Section & TA
Name
Summary
Goals
14
14
16
12
12
PreLab Questions
12
Missed
Points
100
Total Points:
Name, Date, Experiment Title (abbreviated after 1st page) and every page numbered
12
12
Missed
Points
8
16
24
See Lab Guide Chapter 3, Section 3.4 for guidelines in annotating spectra and
Ch 11 for help with interpretation.
POSTLAB QUESTIONS
TOTAL POINTS
16
100
Total Points:
Exp't 15