Table Of ContentTHE SYNTHESIS OF 4- SUBSTITUTED THIANAPHTHENES
A Thesis
Presented to
the Faculty of the Department of Chemistry
The University of Southern California
In Partial Fulfillment
of the Requirements for the Degree
Master of Science in Chemistry
by
David M. Frisch
December 1950
UMI Number: EP41586
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This thesis, written by
tlto ( _ W )
under the guidance of luf&dJFacuity Committee,
and approved by all its members, has been
presented to and accepted by the Council on
Graduate Study and Research in partial fulfill
ment of the requirements for the degree of
HARRY J. DEUEL, ^r.
TTean
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Chairman
TABLE OF CONTENTS
CHAPTER
I. INTRODUCTION . . ..............................
II. DISCUSSION OF RESULTS .......................
Synthesis of 4-keto-4*5,6,7-tetrahydrothia-
naphthene ................................
Grignard reaction.................... . . .
Reformatsky reaction .....................
Leuckart reaction .........................
Schroeter reaction .......................
Horning reaction .........................
Cyanohydrin reaction .....................
III. EXPERIMENTAL.......... .......................
Attempt to cyclicize Y-(2-thienyl)-n-
butyric acid using hydrogen fluoride . .
Reaction of 4-keto-4,5*6*7-tetrahydrothia-
naphthene with Grignard reagents . . . .
Reformatsky reaction of 4-keto-4*5,6*7-
tetrahydrothianaphthene with ethyl
bromacetate ..............................
Leuckart reaction with 4-keto-4*5*6*7-
tetrahydrothianaphthene .................
Attempt to prepare 4-aminothianaphthene
from the oxime of 4-keto-4,5*6*7-tetra-
hydrothianaphthene (XX) .................
iii
CHAPTER PAGE
Attempt to prepare 4-aminothianaphthene
from 4-keto-4,5,6,7-tetrahydrothia-
naphthene azine (XXII) ................. 20
Attempt to prepare 4-hydroxy-4-carboxy-4,
5,6,7-tetrahydrothianaphthene 21
IV. S U MM A RY...................................... 23
BIBLIOGRAPHY........................................ 24
ACKNOWLEDGMENT
The author is indebted to Dr. M. C. Kloetzel for
his long and patient guidance in this investigation.
CHAPTER I
INTRODUCTION
Although many substituted thianaphthenes have been
prepared, only two 4-substituted compounds, 4-hydroxythia-
naphthene (l) and 4-aminothianaphthene (2) have thus far j
been reported. With the synthesis of 4-keto-4,5>6,7-tetra- (
hydrothianaphthene (IV) by Fieser and Kennelly (l) easy j
access to the 4-position through the reactive carbonyl group:
is afforded. The work herein reported was undertaken with t
;the object of preparing a number of 4-substituted thianaph- 1
<
thenes which might possess some properties of biological
interest. For example, 5-aminothianaphthene has shown tuberi
i
culostatic activity (3) and it was thought that the testing
.of the 4-amino compound might prove to be of interest. Also!
4-thianaphthenylacetic acid might be comparable to indole-3-
acetic acid as a plant growth hormone. j
I
The reactions undertaken with 4-keto-4,5,6,7-tetra-
i
hydrothianaphthene were Grignard additions to prepare the ,
4-methyl and 4-phenyl derivatives, the Reformatsky reaction :
to prepare 4-thianaphthenylacetic acid, and finally the :
.Leuckart, Horning, and Schroeter reactions in attempts to 1
prepare 4-aminothianpahthene by a simpler method than that 1
reported by Fries (2). >
CHAPTER II
DISCUSSION OF RESULTS
Synthesis of 4-keto-4,5*6,7-tetrahydrothlanaphthene. >
The preparation of 4-keto-4,5,6,7-tetrahydrothianaphthene
(IV) was accomplished by the method of Fieser and Kennelly
U).
O + qSSt* i
C-O
^
O
W £nr.) o i ,
cm
The yields in the four reactions of the sequence were
:70, 50, 93 and 49 per cent, respectively, as compared with
>
54, 72, 90, and 90 per cent reported by Fieser and Kennelly.
Attempts to increase the yield of II by the application of
,the Martin modification (4) of the Clemmensen reduction fail
ed. Likewise, attempts to use anhydrous hydrogen fluoride
(5) for the direct cyclization of II only resulted In the
recovery of?f-(2-thienyl)-n-butric acid. ;
1
, Grignard reaction. The reaction of 4-keto-4,5,6,7-
tetrahydrothlanaphthene (IV) with Grignard reagents proceed-:
ed smoothly. The two hydroxy intermediates, 4-hydroxy-4- !
!
methyl-4,5,6,7-tetrahydrothianaphthene (V) and 4-hydroxy-4-
phenyl-4,5^6,7-tetrahydrothianaphthene (VI) were unstable i
3
and decomposed within one to three weeks on standing at room
temperature. Dehydration and dehydrogenation of the carbinols
with sulfur (6) produced 4-raethylthianaphthene (VII) and 4-
phenylthianaphthene (VIII) in yields of 8l and 80 per cent re
spectively. Conversion of 4-phenylthianaphthene to the sulfone
(12) (IX) in 79 per cent yield was effected by hydrogen peroxide.
-ir* JJj
0
Reformatsky reaction. In the Reformatsky reaction (15)
of 4-keto-4,5,6,7-tetrahydrothianaphthene (IV) with ethyl bro-
moacetate, the isolated material was not the hydroxy ester but
a mixture of unsaturated esters (X, XI). This loss of water has
been frequently reported in Reformatsky type reactions (15)*
1 J»*rcVM6r
<30 ,gO + <O
q
I
-
(20
cH*r CH-c©^
I7O tpC* ^
Cm)
1^
L ftce
g Q
m
4
No attempts were made to separate the two esters; but upon
saponification, followed by acidification, two acids, m.p.
186° -187° and 107° -109° respectively, were obtained.
1
Both showed the correct analysis for the composition C-^qH^q
O2S. Separation was effected by virtue of the greater
solubility of the lower melting compound in acetic acid.
Ozonolysis of the two isomeric acids would be expected to
proceed in the following manner.
However, ozonolysis of the higher melting compound yielded
no identifiable products. One of the potential ozonolysis
products is 4-keto-4,5,6,7-tetrahydrothianaphthene (IV), but
no trace of this compound or its oxime (XX) was found. The
lower melting compound was not obtained in quantity adequate
for ozonolysis studies.
Dehydrogenation (9) and subsequent saponification of
the mixture of esters (X) and (XI) obtained from the Re
formatsky reaction yielded only one compound, 4-thianaph
thenylacetic acid (XIV) which was easily converted to the
sulfone (12) (XV).
