STUDIES OF THE ABNORMAL REIMER-TIEMANN REACTION

136 Pages·05.001 MB·English

by  WEBB, WILLIAM PAUL

STUDIES OP THE
ABNORMAL REIMER-TIEMANN REACTION
A Thesis
Submitted to the Graduate Faculty
of the
University of Minnesota
by
William P. Webb
In Partial Fulfillment of the Requirements
for the Degree of
Doctor of Philosophy
October 1951
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ACKNOWLEDGMENT
The author wishes to express his sincere appreci­
ation to Dr. Raymond M. Dodson for his advice and
encouragement during the course of this work. He
would also like to thank the United States Government
for help received under the Servicemen's Readjustment
Act, Public Law #3lj.6j and the Research Corporation for
granting a fellowship for the years 19^9-19^1.
William P. Webb
ii
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TABLE OP CONTENTS
Page
INTRODUCTION .................................. 1
HISTORICAL . . . ...................... 5
The Abnormal Reimer-Tiemann Reaction • . • • 5
Use of the Reimer-Tiemann Reaction • • • » • 12
Alkylation . . . .......... . . . . . . . . 17
The Hydrolysis of Vinyl Chlorides by
Sulfuric Acid ......... 22
DISCUSSION OF RESULTS....................... 27
The Preparation of 1-Substituted-2-
naphthols; The Reimer-Tiemann Reaction
with 1-Substituted-2-naphthols • • • • • • • 27
Other Attempts to Synthesize Compounds
Possessing a Quaternary Carbon Atom
from 2-Naphthol • • • • • ............. 4-1
Rearrangement of the Reimer-Tiemann
Product • • . . . . ...................... 5k
EXPERIMENTAL............................... 7^
1 -Methyl -2 -naphthol ................... 75
1-Methyl-l-dichloromethyl-2-keto-l,2-
dihydronaphthalene ................ 7°
1.1-Dimethyl-2-tetralol ........... 77
1.1-Dimethyl-2-tetralone ................... 79
1.1-Dimethyl-2-tetralone Oxime . . . . . . . 79
2-Tetralone ........................ 80
1.1-Dimethyl-2-tetralone ............. 81
1.1-Dimethyl-2-tetralone Oxime . . . . . . . 82
ili
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iv
Page
l-Allyl-2-naphthol ....................... 83
l-(3-Chloro-2-butenyl)-2-naphthol . • • • • 85
l-Allyl-l-dichloromethyl-2-keto-l,2-
dihydronaphthalene •• 86
1-Dic.fciorome thyl-1- (3-chloro-2-butenyl) -
2-keto-l,2-dihydronaphthalene • • • • • • • 87
Reaction of l-Dlchloromethyl-l-(3*"Chloro-
2-butenyl)-2-keto-l,2-dihydronaphthalene
with Sulfuric Acid • • • • • • • • • • • • • 88
Reaction of l-(3-Chloro-2-butenyl)-2-
naphthol with Sulfuric A c i d ............. 89
Reaction of 2-Naphthol with Dimethyl-
chloroethylamine under Reimer-Tiemann
Conditions « • • • • • 89
Reaction of 2-Naphthol with Dimethyl-^ -
chioroethylamlne under C-Alkylating
Conditions • • • • • • • • • • 90
l-Bromo-2-methoxynaphthalene ........ 91
Reaction of l-Bromo-2-methoxynaphthalene
with Dimethyl-0 -chloroethylamine under
Wurtz-Fittig Conditions• • • • • • • • • • 91
n-Butyl Lithium...................... 93
l-Bromo-2-naphthol 94
1-(2*-Dimethylaminoethyl)-2-naphthol • • • • 94
Reaction of l-Methyl-2-naphthol with
Acrylonltrile . • • • 95
2-Naphthyl Benzoate ..................... 9&
2-Naphthyl Acetate • • • • • 97
1-Methyl-2-naphthyl Acetate ............. 97
Fries Rearrangement......... 98
Reaction of 1-Methyl-2-naphthol with
Allyl Alcohol........... 99
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V
Page
9-Ethyl-l,2,7,8-dibenzxanthene . . . . . . . 100
Reaction of 2-Naphthol and Acetone • • • » • 101
1,2,7,8-Dlbenzxanthone • • • • . • . . . . • 101
2-Methyl-l,2-dihydronaphtho(2,l-b)furan . • 102
Reaction of l-Methyl-2-naphthol with
Aldehydes.............................. 103
Reaction of 1-Methyl-2-naphthol with
A lly l Alcohol • • • • < • • « • • • « . . lOlj.
*
Reactions Using p-Toluenesulfonic Acid
as the Catalyst............... . 105
1-Methyl-1-dlehloromethyl-2-tetralone • • • 107
l-Methyl-3,lf-dlhydro-3-naphthole Acid . . . 108
1-Me thy 1-3-naphthoic A c i d ..................109
The Reaction of 1-Methyl-1-dlohloromethyl-
2-keto-l,2-dihydronaphthalene with Base • • 110
lr( oc-Methyl- £-chlorovinyl)-hydrooin-
namlc Acid • • . • • . • • • • • • • • • • • Ill
0-Carboxyhydroclnnamic A c i d ................112
2-C hi or o - 3 -me thyl ,5> -b ©nz tr op one . . . • • 113
-1+
Oxidation of 2-Chloro-3-methyl-l(.,f?-benz-
tropone to Phthallc Acid • • . . . . . • • • 115>
1-Methyl-2,3-benztropolon e . • ll£
BIBLIOGRAPHY .. 1 17
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INTRODUCTION
Besides yielding the expected aldehydes, the Reiner
Tiemann reaction with ortho- or para-alkylated phenols
also yields cyclic hexadienones containing a dichloro-
methyl group on the alkylated carbon atom. This is
known as the abnormal Reimer-Tiemann reaction, and is
a useful method for obtaining compounds containing a
Quaternary carbon atom.
CHi r- ^HC12
•f CHCI3
0
The ratio of abnormal product to normal product varies
with the nature and number of substituents, and with
the type of phenol being alkylated.
The resulting ketones upon reduction give com-
pounds containing a gem-dimethyl group. Therefore, the
reaction provides an ingenious way in which to intro­
duce angular methyl groups into a molecule. The
ketones resulting from ortho substitution give mainly
acidic products when hydrolyzed by base, and these
compounds have proved useful In the synthesis of certain
1
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2
natural products* For example* -terpinene was obtained
<A
through the following series of reactions*
CH3 .CH
CH
CHC12 4- H-Mgl >
Cl 0
HOOC CH3
KOH
CHC12
+
HOOC
KOH
CH3 CH3
The purpose of the present investigation was three*
fold: first, to study the synthesis of cyclic ketones
containing a quaternary carbon atom by means of the
abnormal Reimer-Tiemann reaction with l-substituted-2-
naphthols; second to study the basic hydrolysis of the
compounds obtained in this manner; and third to inves­
tigate other methods of synthesising, from 2-naphthol,
compounds containing a quaternary carbon atom* The
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3
ultimate goal was the preparation of a tricyclic com­
pound containing an angular methyl group. One attempted
synthesis Is outlined in the following equations.
ONa Cl
I
-(- C1-CH2*CHsC-CH3
I II
Cl Cl
I I
CHG12 CH2-CH«G-SH3 CH2-CH«G-CH3
" ^ s0 .OH
r 1
; cNaoH
1 CHCI3
III
HO
VI
The resulting product (VI), which has many characteris­
tics of a sterol— the phenanthrene type ring structure,
a hydroxyl group at C-3, and an angular methyl group at
0—10—-would be a useful intermediate in the total syn­
thesis of steroids from easily obtainable starting
materials*
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In order to carry out the objectives of the re-
fiiearch, it was necessary to study the nuclear alkylation
of 2-naphthols by alkenyl halides, to investigate the
abnormal Reimer-Tiemann reaction with these oompounds,
and to examine the sulfuric acid hydrolysis of vinyl
chlorides*
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HISTORICAL
The Abnormal Re lmer-Tienann Reaction.
The Reimer-Tiemann reaction (1) has long been a
standard method for the preparation of ortho-hydroxy
aromatic aldehydes from phenols by the action of chloro­
form In a basic solution. In attempting to use this
procedure to effect the synthesis of 2,3,5-trlmethyl-
6-hydroxybensaldehyde (VII) from pseudo-cumenol (VIII)
von Auwers (2), obtained the expected aldehyde in only
*>$£ yield, whereas a neutral compound (IX) was found in
1 yield. The analysis of this abnormal product
<°H>Hl2°l2<»* indicated that one carbon atom and two
chlorine atoms had been added to the molecule. Simi­
larly (3, If) as-ortho-xylenol (X), para-cresol (XI),
mesitol (XII), and as-meta-xylenol (XIII), all gave
varying amounts of the abnormal, chlorinated products
(XIV, XV, XVI, XVII), along with some of the expected
aldehydes-. Although phenols such as picric acid (XVIII)
or tribromophenol (XIX) gave no abnormal product,
dlbromo-pseudocumenol (XX) reacted smoothly to give
good yields of a dichlorinated compound (XXI).
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