STUDIES OF THE REIMER-TIEMANN REACTION ON 1-SUBSTITUTED-2-NAPHTHOLS

111 Pages·3.623 MB·English

by  KRESPAN, CARL GEORGE

STUDIES OP THE
REIMER - TIEMANN REACTION
ON l-SUBSTITUTED-2-NAPHTHOLS
A Thesis
Subm itted to the Graduate Faculty
of the
U niversity of M innesota
by
Carl 0. Krespan
In P a rtia l F ulfillm ent of the Requirements
fo r the Degree of
Doctor of Philosophy
August 1952
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I'
1
To my wife
ii
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ACKNOWLEDGEMENT
The author wishes to express h is deep ap­
p reciatio n to Drs. C. P. Koelsch and R. M. Dodson
fo r guidance and encouragement received through­
out the course of th is work. G ratitude is also
due the U nited S tates Government and the American
Cyanamid Company fo r fin a n cial aid received dur­
ing the research.
Carl G. Krespan
iii
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TABLE OF CONTENTS
Page
INTRODUCTION ........................................ 1
HISTORICAL ............................................. 4
The Abnormal Reimer-Tiemann R eaction ................ 4
Reactions of Abnormal Reimer-Tiemann Products 14
C -A lkylation of 2-Naphthol ......................................... 19
Reductive C yclization ..................................................... 20
DISCUSSION OF RESULTS ............................................. 32
P reparation of 1-Substituted~2«naphthols ... 32
The Reimer-Tiemann R eaction on 1-S ubstituted-
2-naphthols .................................................................. 37
Reduction of the Abnormal Reimer-Tiemann
Products ......................................................................... 41
P reparation and Reactions of 1-D iehlorom ethyl-
1- (0 -carb oxyethyl) - 2- ket o-1, 2-dihydro-
naphthalene .................................................................. 54
P reparation and Attempted Hydrolyses of
2-Chioro-3-m ethyl-4 ,5-benzotropone . . . . 57
EXPERIMENTAL ........................................................................................ 63
4-Diethylam Inobutanone-2 .............................................. 64
4-Dimethylaminobutanone-2 ........................................... 64
l-(#-K etobutyl)-2-naphthol ......................................... 65
Reimer-Tiemann Reaction on 1 -(tf-K etobutyl)-
2-naphthol .................................................................... 67
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Page
Reductions of the N eutral Product from the
Reimer-Tiemann R eaction on 1-
(#-K etobutyl)-2-naphthol ................. 69
1- (ft - Cyanoethyl)-2-naphthol ...................................... 71
1-D ichlorom ethyl-l- (^ - cyanoethyl)-2-keto-
1 .2- dihydronaphthalene ...................................... 72
Two Raceraic 4a-D iehlorom ethyl-1,2 ,3 ,4 ,4 a ,7,8,
8a-octahydro-5,6-benzoquinoline
H ydrochlorides (A and B) ................................. 74
D erivatives of the 4a-D iehlorom ethy1-
1, 2,3 ,4,4a,7,8,8a-octahydro-5,6-
benzoquinolines ........................................................ 76
Other Reductions of 1 -D iehlorom ethyl-
1- (^-cyanoethyl)-2-k e to -l,2-
dihydronaphthalene ................................................ 80
Clemmensen Reductions of the 4a-D ichlorom ethyl-
1, 2 ,3 ,4 ,4a, 7 ,8, 8a-octahydro-5, 6-
benzoquinoline H ydrochlorides ....................... 81
A rom atization Experiments .............................................. 86
1-D ichlorom ethyl-l- -carboxyethyl)-2-keto-
1. 2-dihydronaphthalene ......................................... 87
The A ction of Permanganate on 1-D ichlorom ethyl-
1- (f - carb oxyethyl)-2-ket o-1, 2-dihydr o-
naphthalene ......................... 88
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Page
1-Diehl or oinethy 1-1- (^-carboxyethyl)-3,4-
dibrom o-2- te tr alone .............................................. 89
1-D ichlor om ethyl-1- (f - carboxyethyl) - 2-
tetra lo n e ....................................................................... 90
Clemraensen Reduction of 1-D ichlorom ethyl-
1- (p-carboxyethyl)-2-k e to -l, 2-
dihydronaphthalene ......................................... 91
B is- (2-hydroxy-l-naphthyl)-m ethane ..................... 93
1-M ethyl-2-naphthol .......................................................... 94
1-M ethyl-1- di chi or om ethyl- 2-ket o-1 f 2-
dihydronaphthalene ............................................... 95
1-(o<-M ethyl-^-chlorovlnyl)-cis-cinnainlc acid . 96
2-0hloro-3-m ethyl-4,5-benzotropone ..................... 96
Displacement of C hlorine In 2-Chloro-3-
m ethyl-4,5-benzotropone ................................ 97
BIBLIOGRAPHY ......................................................................................... 99
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INTRODUCTION
When an ortho- or para-alkylated phenol Is subjected
to the conditions of the Reimer-Tiemann reactio n , among
the products formed is a n eu tral substance resu ltin g from
the Introduction of a dichlorom ethyl group in to the rin g
at the alkylated carbon.
CHC1
NaOH
These cyclohexadienones arise from what is known as the
abnormal Reimer-Tiemann reactio n .
R ecently i t has been discovered th at 1 -su b stitu ted -
2-naphthols w ill also undergo the abnormal Reimer-Tiemann
reactio n . Since dechlorination of the products leads to
compounds having a m ethyl group attached to a quaternary
carbon atom, the method showed promise as a route to com­
pounds containing an angular methyl group. The purpose
of the present work, then, was to study the abnormal
Reimer-Tiemann reactio n on l-su b stltu ted -2 -n ap h th o ls w ith
the eventual synthesis of polycyclic compounds having an
angular methyl group as the goal.
A ttention was concentrated upon l-(|3-cyanoethyl)-2-
naphthol and l-(£ -k e to b u ty l)-2-naphthol as sta rtin g ma­
te r ia ls . The follow ing schemes in d icate the routes by
which it was hoped the syntheats could be accom plished.
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2
gh2oh2cn ch ci2 ch2ch2cn
CHOI
0 V
ch2ch2(!ch3 GHClg CH2GH2GGH3 *
OH
CHC1,
Sequence B would give a product having many of the
stru c tu ra l featu res of a ste ro l. A phenanthrene skeleton,
hydroxyl, group at C-3, and angular methyl group a t C-10
are a ll present. If successful, th is route could be em­
ployed w ith an appropriately su b stitu ted 2-naphthol as
the s ta rt of a to ta l ste ro l synthesis from read ily av ail­
able sta rtin g m aterials.
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The p o ssib ility of an in te re stin g benzotropolone
synthesis involving use of the abnormal Reimer-Tiemann
reactio n also ex isted . Conversion of l-m ethyl-2-naphthol
to 2-chlor0- 5-m ethyl-4,5-benzotropone was recently ac­
com plished. H ydrolysis of th is tropone, which could lead
d ire c tly to a tropolone, was th erefo re of synthetic in ­
terest.
In keeping w ith these aim s, three l-su b stitu te d -2 -
naphthols were prepared and the Reimer-Tiemann reactio n
on each Investigated. A study of the reactions of the
abnormal su b stitu tio n products, p a rtic u la rly reduction,
was also carried out. F in ally , the fe a s ib ility of the
benzotropolone preparation was Investigated.
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HISTORICAL
The Abnormal Reimer-Tiemann R eaction
O rdinarily the Reimer-Tiemann reactio n (1) is consid­
ered as a method of synthesis of ortho-Hydroxy aldehydes.
When von Auwers (2) used th is reactio n to prepare 2 ,3 ,5 -
triraeth y l-6-hydroxybenzaldehyde (I) from pseudocumenol
(II), however, the expected aldehyde was obtained in only
y ield . The major product (III) was a n e u tral, chlo­
rine-containing compound. A nalysis showed a com position
Ci^HigClgO, in d icatin g the addition of one carbon and two
chlorine atoms to a m olecule of sta rtin g phenol.
NaOH
Subsequent experim ents (3, 4) w ith a number of alky­
la te d phenols, including para-cresol (IV ), a ll gave some
of the abnormal product. When bromoform was employed (5),
the Reimer-Tiemann reactio n on para-alkyl phenols led to
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