The Use of Rhodanine in Organic Synthesis and the Use of Aliphatic Diazo Compounds in Organic Synthesis

189 Pages·6.927 MB·English

by  Dijksman, Derek J

THESIS
submitted to
GLASGOW UNIVERSITY
in fulfilment of the requirements
for the Degree of
DOCTOR OP PHILOSOPHY
by
DEREK J. DIJKSMAH
September, 1951.
ProQuest Number: 13838420
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ACKNOWLEDGEMENTS
The author wishes to express his sincere thanks
to Professor P. S. Spring for his supervision and
interest. Thanks are also due to Dr. G. T. Newbold
for his unremitting guidance in many theoretical and
practical aspects of this work.
The author thanks Messrs. T. and H. Smith, Ltd.,
Edinburgh, for generous gifts of nareotine and
opianic acid.
PARTJC
THE USE OP RHODANINE IN ORGANIC SYNTHESIS
1i 2-Dihydro-1-keto-2-thiaaaphthalene s
SUMMARY. PART I.
The work described in Part I of this thesis resulted
from some exploratory studies leading towards the
synthesis of morphine.
The condensation of rhodanine with aromatic jo-carboxy-
aldehydes and with an £-carboxy-ketone has been studied.
a-Methyl opianate (I; R = R* = OMe, R,f = Me) was condensed
with rhodanine (II) to give 5-(2'-carbomethoxy-3'i4'-
dimethoxybenzylidene)-rhodanine (III; R = R* = OMe, R" =
Me). Similarly a-methyl phthalaldehydate (I; R = R' =
H, R" = Me) and phthalaldehydie acid (I; R = R' = RM = H)
condensed with rhodanine to give £-carbomethoxy- (III;
R = R' = H, R" = Me) and o-carboxybenzylidenerhodanine
(III; R = R' = R" = H) respectively. o-Carboxyaceto-
phenone (IV) on condensation with (II) gave p-carboxy-u-
methy1rhodanine (V). o-Carboxybenzylidenerhodanines
titrated as dibasic acids to phenolphthalein. It has
been shown that the imino-group of the rhodanine ring is
responsible for the second acidic function.
Treatment of £-carboxybenzylidenerhodanines with
sodium hydroxide gave 1:2-dihydro-l-keto-2-thianaphtha-
lene-3-carboxylic acids (VI). Thus (III; R = R' = OMe,
rm = jug) gave 1:2-dihydro-1-keto-7 :S-dimethoxy^-thia-
naphthalene -3-carboxylic acid (VI, R = R' = OMe, R" = H) .
Both o-carboxy and o-carbomethoxybenzylidenerhodanine
on treatment with alkali gave (VI; R = R* = R,f = H) j
similar treatment of (IV) gave 1:2-dihydro-1-ke to-4-
methyl-2-thianaphthalene-3-carboxylic acid (VI; R = R'
H, R" = Me).
TT
«> A / COtR'
V"
c---c^o
s
(II) (ill) s cs
^YCOxH
f
C.OtH
CO,CH3
-GO R
(IV) (v) tH>[___C^*H (VI)
The thianaphthalene acids could be decarboxylated
to give l:2-dihydro-1-keto-2-thianaphthalenes (VII).
The sulphur atom in these thianaphthalenes was readily
eliminated by ammonia and primary amines with the
•formation of 1 *2-dihydro-1-ketoisoquinoline derivatives
(VIII). Thus (VIj R = R' = Rn = H) on heating with
~ -3.- •mft.'tVw I
methyl amine gave 1:2 -dihydro -1 -ketcp-sojquinoline -3-
carboxylic acid (VIII; R = R‘ = H, R« = Me).
Treatment of 7:8-dimethoxy-, 4-methyl-, and unsub­
stitute d 1:2-dihydro-1-ke to-2-thianaphthalene-3-carboxylic
acid with Raney nickel gave respectively 6:7-dimethoxyindan
- iii -
1-one (IXj R = R1 = OMe, Ru = H), 3-methy1indan-1-one
(IX; R = R' = H, R" = Me), and indan-l-one (IXj R =
R' = RM = H). The latter compound was also obtained
by the action of Raney nickel on l:2-dihydro-l-keto-2-
thianaphthalene.
Treatment of 5-benzylidenerhodanine with Raney
nickel gave (a) an unidentified product m.p.l89°,
(b) N-methyl-hydroeinnamamide, and (c) hydrocinnamamide.
5-Benzylidene-3-methylrhodanine on similar treatment
gave a mixture of N-methyl-, and N-dimethylhydrocinnam-
amide. The product obtained from the action of Raney
nickel on 5-benzylidenerhodanine benzoate was not
identified.
An attempt to prepare substituted benzthiophenes by
the alkaline hydrolysis of ^-bromobenzylidenerhodanines
was unsuccessful.
(VII) (VIII) (IX)
CONTENTS
PART I. Page
Introduction........................... 1
Theoretical:
Introduction....................................
Condensation of ortho-Carbonyl Benzoic Acids
with Rhodanine................................... 20
Hydrolysis of o-Carboxybenzylidenerhodanines to
1:2-Bihydro-1-ke to-2-thianaphthalene-3-carboxylic
acids.......................... 27
Decarboxylation of 1:2-Dihydro-l-keto-2-thia­
naphthalene -3-carboxylic acids..................... 33
Conversion of 1:2-Dihydro-1-keto-2-thianaphthalene-
3-carboxylic acids to N-substituted isoQuinoline -
3-carboxylic acids............................... 37
Conversion of 1: 2-Dihydro-1-keto-2-thianaphthalenes
to Indan-l-ones.................................. 40
Condensation Products of Opianic Acid............ 48
Reduction of 1:2-Dihydro-1-keto-7:8-dimethoxy-
2-thianaphthalene-3-carboxylic acid with Lithium
Aluminium Hydride................................ 57
Condensation of Rhodanine with o-Halogeno-
benzaldehydes.................................... 59
Action of Raney nickel on 5-Benzylidenerhodanines 61
Experimental.................................... 65
Bibliography ............................... 136
PART II.
Introduction..................................... 141
Theoretical..................................... 148
Condensation of Diazoacetophenone and Ethyl
Diazoacetate with Amides......................... 148
Page
Condensation of Diazoacetophenone. and Ethyl
Diazoacetate with Ihioamides.................... 152
Experimental................................... 156
Bibliography................................... 169
INTBODUCTION