The synthesis of spiro and bridged aziridines, by Emmett S. McCaskill

MISSING IMAGE

Material Information

Title:
The synthesis of spiro and bridged aziridines, by Emmett S. McCaskill
Physical Description:
Book
Creator:
McCaskill, Emmett Scott
Publication Date:

Record Information

Rights Management:
All applicable rights reserved by the source institution and holding location.
Resource Identifier:
aleph - 22776910
oclc - 14081705
System ID:
AA00022475:00001

Table of Contents
    Title Page
        Page i
        Page ii
    Acknowledgement
        Page iii
    Table of Contents
        Page iv
        Page v
        Page vi
        Page vii
    List of Tables
        Page viii
    Abstract
        Page ix
    Chapter 1. Attempted synthesis of a 1-azabicyclo-[1.1.0]-butane-2-one
        Page 1
        Page 2
        Page 3
        Page 4
        Page 5
        Page 6
        Page 7
        Page 8
        Page 9
        Page 10
        Page 11
        Page 12
        Page 13
        Page 14
        Page 15
        Page 16
        Page 17
        Page 18
        Page 19
        Page 20
        Page 21
        Page 22
        Page 23
        Page 24
        Page 25
        Page 26
        Page 27
        Page 28
        Page 29
        Page 30
        Page 31
        Page 32
        Page 33
        Page 34
        Page 35
        Page 36
        Page 37
        Page 38
        Page 39
        Page 40
        Page 41
    Chapter 2. Attempted synthesis of a benzo-2-azirine
        Page 42
        Page 43
        Page 44
        Page 45
        Page 46
        Page 47
        Page 48
        Page 49
        Page 50
        Page 51
        Page 52
        Page 53
        Page 54
        Page 55
        Page 56
        Page 57
        Page 58
        Page 59
        Page 60
        Page 61
        Page 62
        Page 63
        Page 64
        Page 65
        Page 66
        Page 67
        Page 68
        Page 69
        Page 70
        Page 71
        Page 72
        Page 73
        Page 74
        Page 75
        Page 76
        Page 77
    Chapter 3. Experimental
        Page 78
        Page 79
        Page 80
        Page 81
        Page 82
        Page 83
        Page 84
        Page 85
        Page 86
        Page 87
        Page 88
        Page 89
        Page 90
        Page 91
        Page 92
        Page 93
        Page 94
        Page 95
        Page 96
        Page 97
        Page 98
        Page 99
        Page 100
        Page 101
        Page 102
        Page 103
        Page 104
        Page 105
        Page 106
        Page 107
        Page 108
        Page 109
        Page 110
        Page 111
        Page 112
        Page 113
    Appendix. Spectra
        Page 114
        Page 115
        Page 116
        Page 117
        Page 118
        Page 119
        Page 120
        Page 121
        Page 122
        Page 123
        Page 124
    Bibliography
        Page 125
        Page 126
        Page 127
        Page 128
    Biographical sketch
        Page 129
        Page 130
        Page 131
        Page 132
Full Text











THE SYNTHESIS OF SPIRO AND BRIDGED AZIRIDINES


BY



Emmett S. McCaskill, Jr.














A DISSERTATION PRESENTED TO THE GRADUATE
COUNCIL OF THE UNIVERSITY OF FLORIDA IN PARTIAL
FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY





UNIVERSITY OF FLORIDA
1974

































Copyright by

Emmett S. McCaskill, Jr.

1974














ACKNOWLEDGEMENTS


Several people made significant contributions at appropriate

stages of this study. Working with Dr. James A. Deyrup was a

stimulating intellectual experience. Jim Gill, Bill Szabo and

George Kuta are thanked for their assistance and contributions

of ideas. My graduate committee members, Drs. Butler, Dolbier,

Weltner and Baers were an immense help in their critique of this

research. The several versions of this dissertation were effi-

ciently and insightfully typed by Gerda Covell.

The gestation period of this doctoral study was quite a

sacrifice for my family. I am grateful to my children who, young

as they are, tried to understand it all. I would be remiss if

I did not thank my wife's parents, George and Evelyn Brown and

my parents, Emmett and Rosie McCaskill, for their concern and

support. I am grateful for my wife's understanding throughout

these years. For this, it is a pleasure to be able, at last, to

dedicate this dissertation to all members of my family.










TABLE OF CONTENTS


Page

ACKNOWLEDGEMENTS ............................................... i i i

LIST OF TABLES ................................................. vii i

ABSTRACT ....................................................... ix

CHAPTER I Attempted Synthesis of a l-azabicyclo-[l.l.O]-
butane-2-one ..................................

Introduction ...................................... 1
Discussion ........................................ 5
Conclusion ........................................ 38

II Attempted Synthesis of a Benzo-2-Azirine .......... 42

Introduction ...................................... 42
Proposed Plan ..................................... 45
Discussion ....................................... 50
Summary and Conclusions ........................... 77

III Experimental ...................................... 78

General ........................................... 78
Ethyl c-hydroxy-a-(9-fluorenyl acetate) (22.)....... 79
Ethyl fluorenylidene acetate (2]).................. 80
Ethyl azidoformate ................................ 80
Attempted synthesis of 1,2-dicarbothoxy-3-spiro- 80
(fluorenyl) aziridine ..........................
Ethyl a-bromo-a-(9-bromofluorenyl) acetate 42) .... 80
Reaction of ethyl a-bromo-c-(9-bromof l uorenyl)
acetate with ammonia ......................... 81
a-Bromofluorenylideneacetate (z5) ................. 81
Attempted reaction of a-bromofluorenyl ideneacetate
with ammonia ................................. 81
Ethyl c&-bromo-ca-(9-isocyanatofluorenyl) acetate(26) 81
Ethyl -a-bromo-a-(9-carbethoxyaminof l uorenyl)
acetate (2) .................................... 82
Ethyl-f[-ethoxy-5-spi ro-(9-fluorenyl) oxazolin e]
acetate (31) ................................... 82









Page


4-Carbethoxy-5-spiro-(9-fluorenyl)-2-oxazol done (32) .... 83
Reaction of Ethyl-[2-ethoxy-5-spiro-(9-fluorenyl)-
oxazoline acetate with hydrobromic acid ............... 83
4-Methyl-5-spiro-(9-f1uorenyl)-2-oxazolidone (36) ........ 84
9-Aminofluorene (40) .................................... 84
9-Carbethoxyiminofluorene (37) ........................... 85
9-Carbethoxyaminofluorene (41) ........................... 86
9-Carbethoxyiminofluorene (37) ........................... 86
Fluorenylideneimine (42) ................................. 86
Methyl a-bromo-o-(9-carbethoxyaminofluorenyl) acetate (29) 86
Reaction of Methyl a-bromo-a-(9-carbethoxyamino-
fluorenyl) acetate with alcoholic potassium
hydroxide ............................................. 87
Reaction of 9-Carbethoxyiminofluorene with alcoholic
potassium hydroxide .................................. 87
Attempted Reaction of 9-Carbethoxyiminofluorene
with Benzoyl Peroxide ................................ 87
Attempted Reaction of 9-Carbethoxyiminofluorene
with Ditertbutyl Peroxide ............................ 88
Ethyl a-bromo-o-(9-aminofluorenyl) acetate (44) .......... 88
Ethyl 2-spiro-(9-fluorenyl) aziridine carboxylate (20) ... 88
Sodium 2-spiro-(9-fluorenyl)-aziridinecarboxylate (j6) ... 89
Reaction of Sodium 2-spiro-(9-fluorenyl) aziridine
carboxylate with Thionvl Chloride (Attempted) ........ 90
Anthracene-9, 10-endo-c, p-succinic anhydride (65) ...... 90
Disodium 9, 10-endo-a, p-succinate (67) .................. 90
Anthracene-9, 10-endo-a, p-succinic acid (68) ............ 91
Electrolytic Bisdecarboxylation (General Method).......... 91
Bisdecarboxylation with Lead Tetraacetate (General) ...... 92
Electrolytic Bisdecarboxylation of anthracene-9, 10-
endo-a, p-succinic anhydride .......................... 93
Electrolytic Bisdecarboxylation of disodium 9, 10-
endo-a, p3-succinate ................................... 93
Electrolytic Bisdecarboxylation of 9, 10-endo-a,
p-succinic acid ....................................... 93
Bisdecarboxylation of 9, 10-endo-a, p-succinic acid
with Lead Tetraacetate ................................ 94
R-Methoxyphenylazide (70) ................................ 94
l-(p-Methoxyphenyl)-9, 10-ethanoanthracene Z\2
triazoline (71) ....................................... 95
N-(p-Methoxyphenyl)-9, 10-ethanoanthracene aziridine (72) 95
9, lO-dihydro-9, 10-ethenoanthracene-i1l, 12-di-
carboxylic acid (74) .................................. 95








Page


Dimethyl 9, lO-dihydro-9, 10-ethenoanthracene 11
12-dicarboxylate (73).............................. 96
9, lO-dihydro-9, lO-ethenoanthracene carboxylic
anhydride (75) ..................................... 96
4, 5-[9, 10-anthrylene]-cyclohexene-cis-l, 2-di-
carboxylic anhydride (63).......................... 97
Attempted Electrolytic Bisdecarboxylation of 4,
5-[9, 10-anthrylene]-cyclohexene-cis-l, 2-di-
carboxyl ic anhydride ............................... 97
Attempted Electrolytic Bisdecarboxylation of 4,
5-[9, 10-anthrylene]-cyclohexene-cis-l, 2-di-
sodium carboxylate ................................. 97
Attempted Synthesis of 4, 5-[9, 10-anthrylene]-
cyclohexene-cis-l, 2-dicarboxylic acid ............. 98
Attempted Electrolytic Bisdecarboxylation of 4,
5-[9, 10-anthrylene-cyclohexene-cis-l, 2-di-
carboxylic anhydride with Lead Tetraacetate ........ 99
Meso-2, 3-[9, 10-anthrylene]-l, 4-butanediol (81)...... 99
Meso-2, 3-[9, 10-anthrylene]-l, 4-butane-di-p-
toluene-sulfonate (82) ............................ 100
11, 12 Dimethyl-9, lO-dihydro-9, 10-ethanoanthracene .. 100
1, 2-[9, l0-anthrylene]-cyclohexene-cis-4, 5-di-
carboxylic anhydride (79) ......................... 102
1, 2-[9, 10-anthrylene]-cyclohexene-cis-4, 5-di-
carboxylic acid (80) ............................... 102
Electrolytic Bisdecarboxylation of 1, 2-[9, 10-
anthrylenel-cyclohexene-cis-4, 5-dicarboxylic
anhydride .......................................... 103
Electrolytic Bisdecarboxylation of I, 2-[9, 10-
anthrylene]-cyclohexene-cis-4, 5-dicarboxylic acid 103
Triptycene [9, 10-0-Benzenoanthracene (85) ............ 104
Oxidative Bisdecarboxylation of 1, 2-[9, lO-anthry-
lenel-cyclohexene-cis-4, 5-dicarboxylate anhydride
with lead tetraacetate ............................. 104
4, 5-Dimethyl-[1,2,4,5-(9,10-anthrylene)-cyclo-
hexadiene] dicarboxylate (a2 ) ..................... 104
4, 5-Dimethyl-[4, 5-(9, 10-anthrylene)-cyclohexane-l,
2-1-(p-methoxyphenyl-AZ2-triazoline] dicarboxylate(_77) 105
4, 5-Dimethyl-[9, 10-O-Benzenoanthracene] di-
carboxylate (89) ................................... 106
4, 5-Dimethyl-[4, 5-(9, 10-anthrylene)-cyclohexene-
N-(p-methoxyphenyl)-l, 2-aziridine] dicarboxylate (91)106









Page


Attempted allylic Bromination of 4, 5-dimethyl-
[4, 5-(9, 10-anthrylene) cyclohexene-N-(p-
methoxyphenyl)-1, 2-aziridine] dicarboxylate ........ 107
4-Ethyl -([9, 10-anthrylene)-cycl ohexadiene]
carboxylate (95) ................................... 107
Attempted addition of p-mniethoxy azide to 4-Ethyl-
[1,2,4,5-(9, lO-anthrylene) cyclohexadiene]
carboxylate ........................................ 108
4-Carbethoxy-triptycene (98) ........................... 109
1, 2-(9, 10-anthrylene)-cyclohexane-1-p-methoxy-
phenylA2 triazoline-cis-4, 5-dicarboxylic
anhydride (99) ...................................... 109
Photolysis of 1, 2-(9, 10-anthrylene)-cyclohexane-
1-p-methoxyphenyl-A2' triazoline-cis-4, 5-
dicarboxylic anhydride .............................. 110
4, 5-Dimethyl-[(9, 10-anthrylene)-cyclohexane-l,
2-1'(p-methoxyphenyl)A2' triazoline] di-
carboxylate (103) ................................... 110
4, 5-Dimethyl-[1, 2-(9, 10-anthrylene)-cyclo-
hexene] dicarboxylate (102) ........................ 111I
4, 5-Dimethyl-[9, 10-anthrylene-cyclohexane-N-
(p-methoxyphenyl)-1, 2-aziridine] dicarboxylate (104) 112
Disodium [9, 10-anthrylenecyclohexene-N-(p-methoxy-
phenyl)-!, 2-aziridine] dicarboxylate (105) ......... 112
Attempted esterification of disodium [9, 10-anthry-
lenecyclohexene-N-(p-methoxyphenyl)-1, 2-aziri-
dine] dicarboxylate ................................. 113
Electrolytic Bisdecarboxylation of disodium [9, 10-
anthylenecyclohexene-N-(p-methoxyphenyl)-1,
2-aziridine] dicarboxylate .......................... 113

APPENDIX ........................................................ 114

BIBLIOGRAPHY .................................................... 125

BIOGRAPHICAL SKETCH ............................................. 129













LIST OF TABLES


Table Page

I Ring Strain in Three-Membered Rings ..................... 6

II Substituent Reactions of a-Bromo Carbamates ............. 33


viii











Abstract of Dissertation Presented to the Graduate Council
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Doctor of Philosophy


THE SYNTHESIS OF SPIRO AND BRIDGED AZIRIDINES

By

Emmett S. McCaskill, Jr.

December, 1974

Chairman: James A. Deyrup
Major Department: Chemistry

Attempts were made to synthesize a stable I-azabicyclo-[l.l.O]-

butane-2-one system, and confirm this proposed intermediate in the

aziridine-azetidinone ring expansion. Although the 1-azabicyclo-

([l.l.0]-butane-2-one system was not synthesized, this research re-

sulted in corroboration of the oxazoline-oxazolidone interconversion,

a new cyclization of 3-halo-carbamates and the synthesis of a spiro-

(9-fluorenyl)-aziridine. An explanation of these results is pre-

sented.

Attempts were also made to synthesize a benzo-2-aziridine system

by a Retro-Diels-Alder reaction. This involved the synthesis of a

N-aziridinyl-(9, 10-anthrylene)-cyclohexa-3, 5-diene derivative.

Realizing the importance of synthesizing this compound, the synthesis

of bridged aziridines was pursued initially. We were successful in

obtaining three precursors. The results of this work are discussed.












CHAPTER I


ATTEMPTED SYNTHESIS OF A I-AZABICYCLO-[I.i.O]-BUTANE-2-ONE


INTRODUCTION

A previous investigation by Deyrup and Clough led to the dis-

covery that certain aziridine derivatives undergo ring expansion to

3-chloro-2-azet i dinone (J).








"R
C10













Their work began when an attempt to synthesize a 2-aziridine-carbonyl

chloride (2) resulted in a new path to the 3-halo-2-azetidinone system,

Scheme I. Thus, when the lithium or sodium salt of 1-tert-butyl-2-

aziridine carboxylate (3) was treated with thionyl chloride or oxalyl

chloride in the presence of excess sodium hydride, the resultant pro-

duct was 1-tert-butyl-3-chloro-2-azetidinone (4) in 33% yield. Struct-

ure proof of this azetidinone 4 was based on ir and nmr spectroscopy,

elemental and mass spectral analysis. Further proof of the structure


- 1 -




-2-


Scheme I


0
&0-ONa
V-7
I
1-Bu
3


SOC!2


c-c'

N
it-Bu
2






4tBu
4


was obtained by reduction of the azetidinone 4 with zinc to give

l-tert-butyl-2-azetidinone (5) in 41% yield. Azetidinone 5 was

synthesized from 3-tert-butylaminopropronic acid (6), and thionyl

chloride, Scheme II.

Scheme I I


Zn
4
EtOH


- SOC12 H
-Bu N(CH2)2COOH

5 t-Bu 6




- 3 -


The ring expansion was of both mechanistic and synthetic inter-

est. The similar behavior of thionyl chloride and oxalyl chloride

with the aziridinium salts suggested that in both reactions a common

intermediate is present and opposes intermediates such as 1 or 8.


0
cT^ ^oo

C1 30 C1 0


1 0,
t Bu t-Bu
t-B U tB

7 8


A symmetrical carbonium-type intermediate can also be overruled

since the reaction was found to be stereospecific, Scheme III.

Scheme I II


(CO C12)2


R = CH3;

R H;


R = H
R, = CH3


R = CH ;

R = H;


R = H

R = CH




-4--


An appropriate mechanism, Scheme IV, capable of explaining these

results is the initial formation of the 2-aziridinecarbonyl chloride

(). Interaction of the unshared electron pair on the annular nitro-

gen and the carbonyl carbon results in the formation of a 1-azabicyclo-

[l.1.0]-butane-2-one cation (10). This strained bicyclic ion 10

proposed as the intermediate for this reaction gave 1-tert-butyl-3-

chloro-2-azetidone (4) by a stereospecific attack by chloride ion.

Scheme IV





0
It
C-ONa


1 9B
I _.C_-
t-Bu
0
3 9







I-Bu 0



CF t-Bu




- 5 -


The purpose of this study was to synthesize a stable 1-aza-

bicyclo-[l.l.0]-butane-2-one, establish the intermediate of this

reaction and to investigate the chemistry of this new system.


DISCUSSION

In an effort to select a derivative of a l-azabicyclo-[l.l.0]-

butane-2-one system (Il) that would be stable, strain energies and





R24

II



synthetic routes for stable azabicyclobutanes, aziridines and aziri-

dinones were considered. The stability of the azabicyclobutane ring

2
has been recently demonstrated by Hortman and coworkers. They syn-

thesized and isolated 3-phenyl-l-azabicyclo-[l.1.0]-butane. An estim-

ation of the increase in strain energy for introducing a carbonyl

group into the l-azabicyclo-[1.1.0]O-butane ring system seemed reason-

able. The corresponding values of strain energies for cyclopropane

and the aziridine ring are similar (26.9 and 27.5 kcal/mole3). Wiberg4

has shown that the introduction of a trigonal carbon into a three-

membered ring results in approximately 13 kcal/mole additional strain

energy (Table 1).




-6-


Table 1

Ring Strain in Three-Membered Rings


Compound Strain Energy (kcal/mole)

Cyclopropane 27.5
Methylenecyclopropane 41.0
Cyclopropene 55.0


An equivalent or greater increase in the strain energy of the azabi-

cyclo-[l.l.0]-butane-2-one system was expected but perhaps not to the

extent that it would make the synthesis impossible or greater than

the isolated cyclopropene (55.1 kcal/mole).

In order to stabilize the strained ring system, appropriate R

and R2 groups on the azabicyclo-[1.1.0]-butane-2-one system were

sought. Many ring opening reactions of aziridine may be formulated

as substitutions involving attack of a nucleophile at the aziridine

carbon atom. It seemed reasonable that steric protection of this

carbon atom with large groups would aid in the stabilization of this

ring system. In other highly strained systems such as a-lactones5
6
and a-lactams, tertiary butyl groups have been used with great

success and were considered here. Selection of R and R groups

which would destabilize positive charge at this carbon should inhibit

ring opening. The fluorenyl group seemed to suit these criteria.

Its derivative, l-azabicyclo-[l.l.O]-butane-2-one 12 was chosen

for synthesis.




-7-


NY
0
12


Ring closures from precursors 13, 14 and 15 were considered for
the synthesis of 12, Scheme V.


Scheme V


HN ?R
C=0
x
13


0x0
HN R
X
0
14


X R
00?
HN 0r
15


Base


YHN
0
12




-8-


The first precursor 13 would require synthesis of the spiro-

aziridine and ring closure of the a-lactam ring under appropriate

reaction conditions. The second precursor 14 would necessitate

synthesis of a P-lactam with a suitable leaving group in the 3-posi-

tion followed by elimination of HX to give the bicyclic product 12.

The third precursor 15 would require preparation of an Q-lactam

followed by ring closure of the aziridine to give the product 12.

Precursor 15 was eliminated on the basis of work by Lengyel and

Sheehan who have shown that the greater the steric requirements of

the substituents on N and on C-3, the easier the preparation and

purification of the a-lactam. This has been attributed to greater

thermal stability and lower reactivity towards nucleophiles. N-un-

substituted a-lactams have not been synthesized to date. If the

sodium or lithium salts of 1_6 could be synthesized, Scheme VI,

reaction with thionyl chloride might produce the desired product 12.

If nucleophilic attack by Cl occurs prior to deprotonation, the

Scheme VI



Q Q 0OC1 0 Q

HN HN H PCl
COONa
0 0
16 17 18




12




- 9 -


result should be 18. Proper treatment of 18 with a strong non-

nucleophilic base should give the desired product 12.

In an attempt to synthesize precursor 13, two spiroaziridines,

19 and 20, were chosen. Either one of these spiroaziridines could


EtO-C-N eiP
0 Et
19


O0

C-,
"0 Et
20


oe treated with strong base to produce the desired precursor 16,

Scheme VII.

Scheme VII


NaOH 0


C-ONa


129






20




- 10 -


Seemingly the most feasible way to obtain N-substituted spiro-
aziridines 19 would be to react ethyl azidoformate with ethyl
fluorenylidene acetate (2l), Scheme VIII. Huisgen, Szeimier and

Scheme VIII


~bEt


0
+ N3-C-OEt -- TrEazoIrw


21


hu Or
A


DOc
0I 00Et
EtC Q- 0
11j


8
Mbbius have studied the addition reaction of aryl azides to G, 3-un-
saturated esters and nitriles. Aryl azides could not be used here due
to the difficult removal of aryl group. The reaction of ethyl azido-
9
format with alkenes has been studied by Lwowski and Mattingly. Even
though no examples of a, P-unsaturated esters were given, success with
other azides warranted investigation.




- 11 -


The synthesis of precursor 19 began with the preparation of

ethyl fluorenylidene acetate (21) according to the procedure of
10
Sieglitz and Jossay. Ethyl a-hydroxy-cQ-(9-fluorenyl) acetate (22)

was prepared from 9-fluorenone (_3) and ethyl bromoacetate in a Re-

formatsky reaction, Scheme IX. The product was not isolated but

Scheme IX





0 HO0 CH2
+ ZnBrCH2C OEf A v
0^

23 "0 'Et
22


HOTs Q
C6H6
HA K COOEt
21




dehydrated by a catalytic amount of toluensulfonic acid to give ethyl

fluorenylidene acetate (21) in an overall yield of 91%.

Ethyl azidoformate was allowed to react with ethyl fluorenylidene

acetate (21) in methylene chloride, Scheme X.




- 12 -


Scheme X


0
+ N3-C-OEt CH2CI2
R.T.
I yr.


No Reaction


The reaction was monitored with infrared spectroscopy at one-,three-,

sixjqnd twelve-month intervals. After one-year reaction time, only

starting materials were recovered. The reaction was terminated. The

unreactivity of this alkene may be attributed to the deactivation of

the double bond by the ester group.

Bromination of the unsaturated ester 21_ according to the published
11
procedures of Gilchrist and Rees gave ethyl Q-bromo-a-(9-bromo-

fluorenyl) acetate (24), Scheme XI.

Scheme XI


CCl4
-. Br2 CC1
R.T.


H COOEt


00
Br COOEt
24


H/ COOEt




- 13 -


Synthesis of the unsubstituted spiroaziridine 20 was attempted
by the reaction of ammonia with a, f-dibromo ester 24, Scheme XII.
This approach was patterned after a series of papers by Cromwell and
Scheme XII


BO B H + NH3 0
Br <
Br Br COOEt

24


% 0
HN _
COOEt
20


12 -
coworkers which dealt with the reaction of a, p-dibromo ketones with
ammonia, primary and secondary amines, Scheme XIII.
Scheme XIII


0
R-CH-CH- C-R +
Br Br
Br Br


R'-NH2 ..




- 14 -


The reaction has been shown to proceed not by initial displacement

but by elimination to give the O-bromo-a-p-unsaturated ketone,

Scheme XIV. The ac-amino-p-bromo ketone obtained by the Michael

Scheme XIV


~~NH3 .
R-CH-CH-C-R 3 R-CH=C- C-R
I I "I
Br Br Br




NxNH3

\-v -b
0
II
0 R C-R
II / ^ --7
R-CH-CH-C-R-----\
NH2 Br N
H






addition of the nitrogeneous base with a-bromo-a-p-unsaturated ketone,

cyclizes to the aziridine. Dibrcmides of a, p-unsaturated acids and

their derivatives were shown to follow the same course of reaction.

Reactions of dibromo ester 24 with liquid ammonia for eight

hours did not give the expected aziridine 20. Instead, ethyl

a-bromofluorenylidene acetate (25) was isolated, Scheme XV. This

product had physical and spectral properties identical to those of a




- 15 -


Scheme XV


NH3


Br H
Br COOEt

24


compound prepared by Gilchrist and Rees.'

with ammnonia was unsuccessful, Scheme XVI.

Scheme XVI


Br CdOOEt

25


NH3
//,>


COOEt
20







Br COOEt

25



Further reaction of 25

It is evident in this


HN O
COOEt


20




- Ib -


case, that ammonia is strong as a base to form the intermediate, but

not nucleophilic enough to give ring closure to the aziridine.

Another synthetic approach to the aziridine precursor 19 en-

tails the nucleophilic displacement of a bromide by cyanate to give

the Dromo-isocyanate, Scheme XVII. This bromo-isocyanate can react

Scheme XVII


I I
Br-9- Br-
Br Br


I I
+ OCN -C C-
I
N Br
II
C
I)
0


ROH


Base


NH Br
C=0
00
6
R


W
C=O
0
R


with alcohol to give a bromo-carbamate. Subsequent cyclization with

a base can give the N-substituted aziridine. The dibromo ester 24

was then treated with silver cyanate, Scheme XVIII. The product 26

was isolated as deep yellow oil in yields that varied from 70 85%




- 17 -


Scheme XVIII


0^I'~ +
Br H
Br COOEt

24


Et2
AgNCO E0 ,H
R.T.H
O=C=N I^
gr COOEf
Br

26


(depending on the quality of silver cyanate). As expected, 26 was

not the only product. Since both bromines could be displaced by cy-

anate ion, it was speculated that the other isomer 27 would also

be present. There was no advantage in separating these isomers be-





Br H
(COOEt


27



cause ring closure of either isomer would give the same desired aziri-

dine precursor. One other product, ethyl fluorenylidine acetate (21)

was present in the reaction mixture. Even though the ester 21 was

not isolated, the nmr spectrum showed a vinyl proton at 6.63cf and an

aromatic proton at 8.92tef situated in the deshielding cone of the









carbonyl group of the ester.

The major product 26 was characterized by conversion to the

carbamate, Scheme XIX. Warming the isocyanate 26 in the presence

Scheme XIX




=0 EtOH *r
00
0=-C=N \XX / >
r COOEt Br COOEt

26 28









of ethanol for a few minutes gave ethyl Q'-bromo-a-(9-carbethoxy amino-

fluorenyl) acetate (28) in excellent yield. The carbamate 28 was

characterized by elementary analysis, nmr and ir spectroscopy and

mass spectral analysis. The structure of isomer 26 is supported

by both chemical and mass spectral data. As demonstrated earlier,

a bromine atom substituted on the beta position of dibromo ester 24

should dehydrohalogenate quite easily. Thus, if the major product

is 28, this isomer should not dehydrohalogenate under these condi-

tions. The carbamate 28 was treated with triethyl amine in benzene,

Scheme XX.


- la -




- 19 -


Scheme XX


0 0

EtOC. COOEt N(Et)3


28



Only starting material was recovered.


No Reaction


9H 9H
Me0- C-N" R Z
MeBr COOEt

29






A high resolution mass spectrum of methoxy derivative 29 showed at
base peak at 238 (m/e calculated C5 H 12NO = 238.0867; found 238.0879).

Structure 30 may be assigned to this fragment. Since there are




- 20 -


+NH
C=0
I
OMe

30


no peaks between 405 and 238 mass units, this fragment probably was

formed as depicted in Scheme XXI.

Scheme XXI


00-
10 H \ H
Me O-C-N^ r, I.CO
Me Br C OOEt



29





m/e =405


+NH
I
C=0
I
OMe

30





m/e = 238


Ring closures of 26 and 28 to the aziridine with ethoxide

in ethanol were attempted. The expected aziridine 19 was not ob-




- LI -


stained, but a 2-oxazoline 31 was isolated in 80% yield, Scheme XXII.
Scheme XXII


Br COOEB


Et O.IV0 C OQB


EtO
EtOH


O- 00
11 H
Et O-C-NC
Br COOE
28


00
Et O-( -N
0 COOE1




- 22 -


It has been shown that cyclization of N-(2-substituted alkyl)-carboxy-

amide may proceed by two pathways, Scheme XXIII. The first pathway

Scheme XXIII


L
I I
i) -y-9-
HN-COOR






L
I I
2) -c C-
I I
H-N
CC=0
6
R


Strong
Base







'I


v
c=O
OR





F--\
N "Y0
V
0
R


yields a 1-acyl aziridine and the second leads to the formation of
oxazolines.

Instances in which aziridines are formed rather than oxazolines
have been attributed mainly to two factors.13 Decreased resonance

stabilization of the anion resulting from the removal of a proton




- 23 -


from the mono-N-substituted urethan apparently favors three-membered

ring formation. The second factor relates to leaving groups effect-

iveness. The formation of aziridines are facilitated by very effect-

ive leaving groups such as tosylate and mesylate. The examples

studied also involved trans groups on six-membered rings. The dis-

tinguishing factors between the two pathways may be more complicated

and need further investigation.

14
Katchalsky and Ben Ishai have shown that P-halocarbamates

may be converted to 2-oxazolidones by pyrolysis at 120 to 200 C,

Scheme XXIV.

Scheme XXIV




H 0
R- C R
I __ A_6
HN H------- ____
C=0

R 0








Heating the carbamate 2_ at 200C for five minutes gave the

expected 2-oxazolidone 32, Scheme XXV. The by-product, ethyl

bromide,could be detected when the reaction was conducted in a Carius




- 24 -


Scheme XXV


0C 0 2000C
EtOOC-0 I
Br COOEt


0 pCOO E
0


29


tube Hasnerandcowoker15
tube. H1assner and coworkers have shown that the pyrolysis of methyl
N-(trans-2-iodocyclohexyl) carbamate (33) gives a 2-oxazolidone 34
melting at 55 56C, Scheme XXVI. The reported melting point for
Scheme XXVI



N-CO Me

x N O e ,,.-N
A ,,.._0
v '. ...""""0X




- 25 -


cis-cyclo-hexano[b]-2-oxazolidone (34) is 55 C; the isomeric trans-

cyclohexano[b]-2-oxazolidone melts at 110 C 5. This reaction

establishes the fact that an inversion of the iodine-bearing

carbon is involved in the pyrolytic conversion of iodo-carbamate

to 2-oxazolidones and with this evidence Hassner proposed the follow-

ing mechanism, Scheme XXVII. If this mechanism is correct, it

Scheme XXVII


HH
cx ~N-COMeQ N
N 0e



33 35
/



aH
Q=0 + Mel


34



should be possible to convert a 2-oxazoline to a 2-oxazolidone with
the addition of HBr under anhydrous conditions, Scheme XXVIII. This
conversion was then carried out with 2-oxazoline 31 in ether pre-




- 26 -


Scheme XXVIII


HBr


NOCH3
OCH3


HN^ o

0'CH3

Br


----0
v HN O

0


+ CH3Br





viously saturated with dry HBr. The isolated product was the 2-oxa-

zolidone 32, Scheme XXXIX. These results support the reaction inter-

Scheme XXXIX


HBr .
EtOH


0HN OCCOOEt
00


32


mediate 35 proposed by Hassner and coworkers.
16
Hassner and other workers have synthesized a large number of

aziridines by cyclization of iodocarbamates with a base, Scheme XXX.




- 27 -


Scheme XXX


H
cX N COOMe NaOH


QNH


Treatment of carbamate 28 under similar conditions did not give
the expected aziridine 20. Instead, 2-oxazolidone 36 and 9-
fluorenone 2? were isolated, each in 20% yield, Scheme XXXI.
Scheme XXXI


10a
H H
EtOON COOE
Br COQEt


q NaOH ,o
A HN ".H
0CH3
^0


36


This reaction was quite unique in that the total process involved the
formation of a carbon-carbon bond on a carbon which contains a nitrogen
atom. Since this reaction has potential synthetic utility, attempts


+ 23




- 28 -


were made to investigate in detail its mechanism. Anionic and cationic
rearrangements were considered but do not reasonably explain these re-
sults. As a working model a radical mechanism was proposed because
alkyloxy radicals are stable intermediates and account for the pro-
ducts, Scheme XXXII.
Scheme XXXII


00OH
H H
EtOOCN X
Br COOEt
28




OoD




RH


36


~H
+ C -COOEt
r^BrI
N
C=O
6
Et
37

R-


0 + RH
N
I .
C-O-C HCH3
!1
0

38




- 29 -


In this proposed mechanism, hydroxide ion first abstracts the proton

from the amide nitrogen to give 9-carbethoxyiminofluorene (37). The

resulting anion is probably destroyed under reaction conditions.

The intermediate 37 reacts further in an oxidative or radical chain

process to give radical 38 which cyclizes to 39 and subsequent

hydrogen abstraction gives the product 36. Because the reaction

conditions were strongly basic, radical scavengers could not be used

to confirm the radical process. In order to investigate the mechanism

of this reaction 9-carbethoxyiminofluorene 3J was synthesized and

subjected to free radical initiators.

9-Carbethoxyiminofluorene 37 was synthesized by two methods.

The first method was the synthesis of 9-(carbethoxyamino) fluorene 41,

Scheme XXXIII, by the reaction of 9-aminofluorene 40 with ethyl chloro-

Scheme XXXIII







0Y: + Ci-COOEt C 6H6
NH2 NH
I
CkO
40 I
OEt

41




- 30 -


17
format utilizing the published procedure of Neish. Oxidation of

41 _with activated MnO according to the procedure of Deyrup and Gill18

gave 9-carbethoxyiminofluorene (37) in acceptable yield, Scheme XXXIV.

Scheme XXXIV


HN
C=0O
OEt

41


MnO2
C6H6


N
CO=0
OEt


37


In a second method, 9-iminofluorene (42) was synthesized from

ammonia and 9-fluorene (23) at 165 C, Scheme XXXV. Subsequent re-

Scheme XXXV



No 15H CICOOEt 37


0 N


action of imine 42 with ethyl chloroformate gave the desired 9-carbo-

thoxyiminofluorene 37.




- 31 -


The reaction of 9-carbethoxyfluorene 37 under the above con-

ditions did not give the desired 2-oxazolidone 36. The only product

isolated was 9-fluorenone (23) in 20% yield, Scheme XXXVI.

Scheme XXXVI


aq. NaOH


c=O
I
OEt

37


a 0
0

23


19
Urry and coworkers19 have studied the free radical reactions of

alcohols with alkenes. The radical chain process involved the formation


-- CH2=CHR


t-BuO)2 .


OH
I
R-C-CH2CH2R
H


of alkyoxy radicals and subsequent attack on the alkene by the radical.


OH
IS
RCH2OH + CH2:CHR R-CH-CH2CHR


RCH2OH




- 32 -


It was found that displacement was on the hydrogen attached to the

carbon bearing the primary and secondary alcohols. Ethers have also
20
been shown to react with alkenes under radical conditions, Scheme

XXXVII.

Scheme XXXVII


Bz202


0

CH2(OCH3)2 + 0

0


H 0
(CH3 O)2C


0


The reaction of 9-carbethoxyiminofluorene (37) with benzoyl peroxide

and tert-butyl peroxides under similar reaction conditions were un-

successful and only starting material was recovered, Scheme XXXVIII.

Scheme XXXVIII


Bz202
t-BuO)2 v


No Reaction


0:0
N
I
C=0
I
OEt
37










In a final effort to explore the mechanism, some substituent

reactions were investigated. These data are summarized in Table II.

Table II

Substituent Reactions of o-Bromo Carbamates







Solvent
H I NaOH Q
ROC HN
() Br COOEt L0o
0










R Solvent Yield (%)
Et EtOH 20 20
Me EtOH 20 20
Me MeOH 0 2


As shown earlier, the 2-oxazolidone and fluorene are produced in equal

amounts. Substituting a methoxy in the carbamate portion of the

molecule using ethanol as the solvent produced no change in the yield

of products. This showed that transesterification was quite rapid.

However, changing the solvent to methanol did not give the expected

product 43, but instead gave only 9-fluorenone (23), Scheme XXXIX.


- ->J ~




- 34 -


ORP
HN -
0-
43


Scheme XXXIX


9H H H
MeQOON BrCOl
Br C -~


0r;0
0


29


Since the carbamate 28 did not give ring closure to the desired
aziridine 19, hydrolysis of the isocyanate to the amine was attempted.
Treatment with an appropriate base could possibly cause ring closure
of a-amino-p-bromo derivative to the spiroaziridine 20. Hydrolysis




- 35 -


of bromo-isocyanate 26 with 47% hydroiodic acid gave the desired

bromo-amine 44 in 50% yield, Scheme XL. This bromo-amine 44 isolated
Scheme XL




~~~HI HN
o^ }-( HI i -f
Acetone H N

O=C=N HXOE "N"I
Br COOEt Br COOEt

26 44







as a colorless oil. The structure is supported by ir and nmr spectro-

scopy.

The cyclization of the a-amino-a-(9-bromofluorenyl) acetate (44)

was finally accomplished. The reaction of 44 with triethyl amine at

room temperature using ethanol as the solvent gave ethyl-2-spiro-

(9-fluorenyl) aziridine carboxylate (20) as white crystals in 98%

yield, Scheme XLI. This structure is supported by ir, nmr, and mass

spectral analysis. The nmr spectrum was interesting and merits some

comment. The N-H proton appeared at 2.58cf as a broad doublet

(J=9Hz). The proton on C-3 appeared at 3.43c" also as a broad doublet




- 50 -


Scheme XLI






N(Et)3
0 'EtOH
H2N H 3Days HN
Br COOEt COOEt


44 20









(J=9Hz). On addition of D 0 the 2.58J resonance disappeared and the

doublet at 3.43JC collapsed to a singlet. This last result elegantly

supports the assigned structure of the spiroaziridine 20.

Following the synthesis of the spiroaziridine 20 as discussed

above, an attempt was made to convert 20 to the sodium salt according

to the reaction conditions of Deyrup and Clough with the intent of

obtaining the l-azabicyclo-[l.l.O]-butane-2-one following subsequent

reaction with thionyl chloride.

Ethyl 2-spiro-(9-fluorenyl)-aziridine carboxylate (20) was

refluxed in aqueous alcoholic sodium hydroxide for one hour. The

sodium salt 1_6 was isolated as a white powder in quantitative yield,




- 37 -


Scheme XLII. This structure is supported from spectral analysis.

Scheme XLII


HN
COOEt


NaOH


HN
COONa


20


Sodium 2-spiro-(9-fluorenyl) aziridine (16) was treated with

thionyl chloride following the procedure of Deyrup and dClough. On

work-up no products could be identified by nmr spectroscopy. It

appeared that thionyl chloride had caused total destruction of the

molecule. The use of alternative reaction conditions at low temper-

atures using different proton scavengers were without success.
21
Tomalia studied the reaction of some N-unsubstituted aziri-

dines with thionyl chloride, Scheme XLIII. He found that by react-

ing equimolar amounts of aziridines and triethyl amine with thionyl




- 38 -


Scheme XLIII




S 02CI2 I
V + Et3N 1,50C > -S-C J
N
H CCI4




25 CI CH2CHI N;S40
250C




chloride at reduced temperatures it was possible to trap and character-

ize the new class of aziridine derivatives, l-(aziridine) sulfinyl

chlorides. When these compounds stood at room temperature for several

hours, 2-chloro-N-sulfinyl ethylamine was isolated. Although none of

these derivatives were isolated, this doas suggest that there is

probably an attack of the thionyl chloride on the nitrogen which

changed the reaction path.

CONCLUSION

Although the l-azabicyclo-[.l.O]-butane-2-one was not syn-

thesized there are at least two approaches which might warrant future

study. The first is the ring closure of the a-lactam ring. Since

the synthesis of this ring involves the formation of a N-C bond and

removal of an OH group in 16, this is closely related to the syn-

thesis of peptide with carbodiimide derivatives, Scheme XLIV. Since




- 39 -


Scheme XLIV


RCOOH -6 RNH2 + R N=C=N R


0 H
R-C- N-R

+

H 0 H
R N-C-N R


aziridines are unstable to acid, the free acid derivative of 16 can

not be generated. If, however, the carbodiimide could be activated

so that the first step is no longer acid dependent, a similar reaction

may occur with the aziridinium salt 16. An ideal reagent would be

a methylated carbodiimide 45. If the methylated carbodiimide 4.




CH
1 3
R-N= C=N-R
x"

45





is allowed to react with 16, the desired product 12, sodium salt

of the anion and a methylated urea 46 should be formed, Scheme XLV.




- 40 -


Scheme XLV


C+
OO*
H
COONa
16


CH3
R N=C=NR
+
X-

45


N P
0
12
+
CH3 0 1
R N- C-NR
46


Syntheses of methylated carbodiimide are presently being investigated.
The second approach utilizes precursor 14, the synthesis of 3-lactam.
This is an attractive route in that the amine 44 has been synthesized.
Thus, base hydrolysis followed by acidification to give the P-amino
Scheme XLVI


0I ) OH" 0,(T
2) H2 v
H2N B H H2N" H
Br COOEt Br COOH


41


cc,

0
H _Brr
0
48


41




41 -






acid 4_ and treatment with a carbodiimide under appropriate reaction

conditions should give the 3-bromo-azetidinone 48. Subsequent treat-

ment of 43 with a strong base, but poor nucleophile, might give the

1-azabicyclo-[1.1.0]-butane-2-one system 12, Scheme XLVI.












CHAPTER II


ATTEMPTED SYNTHESIS OF A BENZO-2-AZIRINE


INTRODUCTION

Considerable attention has been given to the chemistry of small

strained heterocyclic ring systems. The 2-azirine ring system 49

is one that has received considerable attention. A large number of


VH
XN

H
49



22
recent attempts have been directed toward its synthesis, but the

system has neither been isolated nor trapped. This ring system is of

theoretical interest since, if planar, it is a cyclic conjugated
23
structure containing 4TT electrons. Huckel's rule23 predicts anti-

aromatic character. Since 1-azirines are well known, it does not

seem reasonable to attribute the non-existence of 2-azirines ex-

clusively to strain energy. The instability of the 2-azirine system

could probably be attributed to an unfavorable electronic property


- 42 -




-43,-


that exists within this molecule. The aim of this research was to

synthesize the related benzo-2-azirine system (50).



C |N-R


50



The strategy selected was to synthesize a benzo-2-azirine (50)

via a Retro-Diels-Alder reaction, Scheme XLVII.

Scheme XLV I


A


NR 52
50 52


A derivative of N-aziridinyl-(9, 10-anthrylene)-cyclohexa-3, 5-diene

(51) was selected so that formation of benzo-2-azirine (0) would

also yield anthracene (52) as a by-product and thus provide the

driving force in this synthesis.




-44-


Benzopropene (53), which results from fusion of cyclopropene







53




to a benzene ring is the parent and most highly strained member of

the benzocycloalkene series. 4 The strain energy has been estimated
25
to be at least 45.5 kcal/mole greater than cyclopropane.25 Nonphoto-

chemical synthesis of benzocyclopropenes resulted from the work of

Vogel, Grimme and Korte.26 Pyrolysis of 1:1 adducts 54 of 1, 6-

methano[lO]-annulene with dimethyl acetylenedicarboxylate gave benzene-

cyclopropene (53) in 45% yield, Scheme XLVIII.

Scheme XLVIII


O400C


MeOOC-


r+ j'>COOMe
Kj--C 0ACOOMe


53


54




- 45 -


While this work was in progress, a related Retro-Diels-Alder
1 27
approach was published. Klarner and Vogel attempted to prepare an

antiaromatic benzo-2-oxirene (56) which resulted in the isolation of

a rearrangement product 5Z, Scheme XLIX. They concluded that isomeri-

zation of 55 to 51 constituted a suprafacial 1, 5-sigatropic shift

which is symmetry allowed.

Scheme XLIX






56

50-100C

N C 00
NC% < 0

NCC
55NC%


57



PROPOSED PLAN

The precursor 1, 2, 4, 5-(9, lO-anthrylene)-cycluhexadiene (58)

was chosen to initiate the synthesis of the derivative of N-aziridinyl-

(1, 0lO-anthrylene)-cyclohexa-3, 5-diene (51). If 58 could be syn-

thesized, selective addition of azide to the more strained double

bond could give the bridged triazoline 59, Scheme L.





















Scheme L









N3R Q


58 59




Whereas unactivated olefins are sluggish toward aryl-azides, strained

bicyclic systems, on the contrary, are particularly reactive.28 The

triazoline 59 could easily be converted to the bridged aziridine 60

either thermally or photochemically, Scheme LI.










Scheme LI











R N-R
N lhv or




59 60




The bridged aziridine 60 could then be brominated to give the di-

bromo-addition product 61 or could be treated with N-bromosuccinimide

(NBS) to give the allylic brominated product 62, Scheme LII.

Scheme LI I


60


- 47 -




- 48 -


Bromination of unsaturated aziridines has been accomplished at low

temperature by Paquetteand Kuhla.29 Successful synthesis of 61J or

62 and subsequent treatment with base might give the desired pro-

duct 51, Scheme LIII.

Scheme LIIIl





61


N-R

61 Base .Tv



6 2>51














The synthesis of precursor 58 from the anhydride 63 was planned

by either electrolytic or oxidative bisdecarboxylation of 6. or the

diacid 64, Scheme LIV. Bisdecarboxylation and azide addition are two

key steps in this proposed synthesis. A model compound was chosen to




- 49 -


Scheme LIV















Elect. or

Pb(OAc)4


58


64


investigate the problems involved and to find appropriate reaction

conditions by which precursor 58 and bridged aziridine 60 might be

synthesized. The model compound chosen was anthracene 9, 10-U, P-

succinic anhydride (65.).


63




- 50 -


65


DISCUSSION

Anhydride 65 was synthesized according to the published pro-

cedure of Bachmann and Kioetzel, Scheme LV, by the reaction of

Scheme LV


52


0 0
+uio


0
66


A
C6H6


65




- 51 -


anthracene (52) and maleic anhydride (66). The anhydride 65 was

then converted to the disodium salt 67 and dicarboxylic acid 68.

Electrolytic bisdecarboxylation of 665, 67 and 68 gave 11, 12-

etheno-9, 10-dihydroanthracene (69) in 25 30% yield. Oxidative bis-

decarboxylation with lead tetraacetate of 65 and 68 gave approximately

the same results, Scheme LVI. Isolated products obtained from the

Scheme LVI


Elect, or

Pb(OAc)4


68




- 52 -


electrolytic method were cleaner and did not require further puri-

fication. Of significance in the oxidative method is lactone forma-

tion in bridged compounds containing proximate double bonds, Scheme LVII.

Scheme LVII









COOH Pb(OAC)4
COOH O 0
O 0







It is reported that in the oxidative bisdecarboxylation, lactones are

formed. 3 The electrolytic method is usually favored for bridged bi-

cyclic ring systems.

Following the successful bisdecarboxylation of 6 and its deri-

vatives 67 and 68, the 1, 3-dipolar cycloaddition reaction of a-

methoxyphenyl azide (70) warranted investigation. The selection of

azide 70 was based on the following factors: 1, 3-dipolar cyclo-

addition reaction of aryl azides has been characterized and its
32
mechanism confirmed by Huisgen ; the methoxy group in an nmr spectrum





- 53 -


identifies the azide additions, and; the reactivity of azides with

deactivated alkenes has been shown to increase with electron donating
33
groups. The addition of p-methoxyphenyl azide to II, 12-etheno-9,

10-dihydroanthracene gave the triazoline 71 in 57% yield. Photolysis

of the triazoline 71 with a sun lamp gave the expected aziridine 72

in 50% yield, Scheme LVIII.

Scheme LVIII



_OMe


H P
N H




OMe
69 70 71l




OMe



hv "
Acetone




- 54 -


Synthesis of the anhydride 63 began with the preparation of 11,

12-dicarbomethoxy-9, 10-dihydroanthracene (73) according to the pro-
34
cedure of Diels and Alder, Scheme LIX. Saponification followed by

Scheme LIX


COOMe


MeOOC

{J) + MeOOCC=CCOOMe c


52


neutralization to the diacid 74 and subsequent heating with acetic

anhydride gave the unsaturated anhydride 75 in quantitative yield,

Scheme LX. According to the published procedures of Diels and

Scheme LX


NaOH
HCI


Ac2O


74.


75




- 55 -


Friedrichsen35, anhydride 63 was synthesized and isolated in 95%

yield by reacting 75 with butadiene, Scheme LXI.

Scheme LXI


75


1O0C
C6H6


63


Bisdecarboxylation of anhydride 63 with both oxidative and electro-

lytic methods was not successful. Only starting material was recovered,

Scheme LXII. The anhydride 63 was then converted to the disodium

Scheme LXII


Elect, or Pb(OAc)4


63


No Reaction




- 56 -


salt 76. Acidification of the disodium salt 76 did not give the

expected dicarboxylic acid 64, but instead regenerated the anhydride

63. Electrolysis of the disodium salt 76, Scheme LXIII, also gave

Scheme LXIII


HCI


63 NaOH


Elect.


63


the anhydride rather than the expected diene 58. Tetramethyl succinic

anhydride 36(7Z) is formed by the hydrolysis of the diester with hydro-
37
bromic acid. Dialkyl maleic acids exist only in the form of their

anhydrides (78, R = methyl, ethyl, or phenyl) which are formed spon-




- 57 -


78


taneously upon acidification of aqueous solutions of the salts of the

acids.

An alternative approach to the synthesis of precursor 58 is to

synthesize the isomeric anhydride 79. Bisdecarboxylation of 79 or


79

its dicarboxylic acid 80, Scheme LXIV, might give the desired pre-

Scheme LXIV



COOH
HOOC I :\


Elect.


58




- 58 -


cursor 58.

The synthesis of anhydride 729 began with the preparation of

anthracene 9, 10-endo-a, p-succinic anhydride (a), and subsequent

reduction with lithium aluminum hydride in THF.38 The resulting

diol 81 was converted to the ditosylate 82, Scheme LXV, and

Scheme LXV


65 LAH


TsCI


82


thereafter, synthesized in good yield by the reaction of anthracene

(52) with cis-1, 4-dihydroxy-2-butene,39 Scheme LXVI. The ditosylate 82

Scheme LXVI


H20H 1850C


(CHOH


52





- 59 -


was then treated with 7% sodium hydroxide to give dimethylene-9,

10-ethanoanthracene (84) and a by-product ether 83, Scheme LXVII.

Scheme LXVII


82 7%NaOH


84


83


Separation of 84 from 83 by column chromatography and subsequent re-

action of 84 with maleic anhydride (66) illustrated in Scheme LXVIII

Scheme LXVIII


A


0

+ 0
0
66




- 60 -


40
gave the desired precursor 79 in 86% yield.

The diene 58 was unobtainable via bisdecarboxylation of an-

hydride 79 and triptycene (85) was isolated in low yield, Scheme

LXIX.

Scheme LXIX


58


79


Elect.


Bisdecarboxylation of the diacid was then investigated. The anhydride

79, Scheme LXX, was treated with aqueous sodium hydroxide and aci-

Scheme LXX


I) NaOH
2) HCI


80




- 61 -


fiction gave the dicarboxylic acid 80 in 92% yield.

Scheme LXXI shows oxidative and electrolytic bisdecarboxylation

Scheme LXXI







COOH
HOOC

Elect. or
Q Pb(OAc)4 Q


80 85







which gave triptycene (85) in low yield. Triptycene could have been

formed by one of two pathways: bisdecarboxylation to give the diene

58 and subsequent oxidation at the anode surface, or, stepwise de-

carboxylation of one carboxyl group to give a double bond conjugated

with the first, followed by decarboxylation of the second carboxyl

group to give 85.

In the hope that ester groups might stabilize the diene system,

compound 86 was chosen for synthesis. The Diels-Alder reaction of

dimethylacetylene dicarboxylate with 11, 12-dimethylene-9, lO-ethano-9,




- 62 -


MeOOC






86


1-dihydroanthracene (84), Scheme LXXII, gave 42% yield of 86. The

Scheme LXXII


+ MeOOCC^CCOOMe


diene derivative 86 was then treated with k-methoxyphenyl azide, in

a Carius tube for seven days at 80 0C. The resultant triazoline 87,

Scheme LXXIII, was isolated in 71% yield.


Z 40




- 63 -


Scheme LXXIII


MaOO
EtOAc
A .


At 100C products 88, 89, and anthracene (52) were separated using


Me lOK-N=N- _Ome

88 Q
89

column chromatography. The Retro-Diels-Alder by-product 20 was not

detected in the reaction mixture.


MeOOC
MeOOCa


0M
OMe
90


N3

+ 0
OMe

70


87




- 64 -


0
Photolysis of triazoline 87 with a sun lamp in acetone at 25 C

gave the desired aziridine 91, Scheme LXXIV, in 81% yield. The nmr

Scheme LXXIV


MeO


COOMe


hv
Acetone


spectra showed interesting changes of the diene 86 to the triazoline

87 and finally to the bridged aziridine 2j. The three absorptions

of interest were the aromatic protons, the bridgehead protons and ithe

methyl ester protons. In diene 86 the aromatic region showed a

symmetrical absorption of 8 protons, a singlet for the bridgehead

protons, and a singlet for the 6 protons of the two methyl ester

groups. In the triazoline 87 the aromatic region became quite complex




- 65 -


as it increased to 12 protons with the bridgehead and methyl esters

protons appearing as two very close singlets. On photolysis of the

isolated aziridine 91 the aromatic region separated into two por-

tions, an unsymmetric 7-proton multiple and a 4-proton A-B quartet

that was shielded. The bridgehead and the methyl ester protons

appeared as singlets with the bridgehead protons being slightly

more shielded with essentially no change in the ester groups.

Bromination reactions of aziridine 91 were then investigated.

The addition of bromine gave substitution products as depicted by

nmr and mass spectroscopy and was not further pursued. It is re-

ported that bromination of p-methoxytoluene with N-bromosuccimide

in carbon tetrachloride with benzoyl peroxide as the radical initia-
41
tor gave 65% yield of p-methoxybenzyl bromide, Scheme LXXV.

Scheme LXXV





CH3 CH2Br


f3 + NBS CC 4N
OH ABzW0P.
OCH3




- 66 -


Allylic bromination of 21 was then investigated. The reaction of 91

with N-bromosuccimide and benzoyl peroxide did not give the desired

product 92, Scheme LXXVI. Apparently, the two bromine atoms had

Scheme LXXVI


MeOOC


92


91 NBS, CC4
Bz2z0

MeOO0


1dOMe











Br2
e A'L-OMe


93


substituted on the aromatic ring, based on nmr and mass spectral

analysis. The exact substitution pattern was undetermined. It

appeared that the ester groups might have deactivated the allylic





- 67 -


position and that the most reactive site within the molecule 91

was the aromatic ring with the methoxy group substituent.

In an effort to facilitate allylic bromination, compound 94

was selected. The single conjugated ester group would probably

still stabilize the diene. Also, by having only one ester group,

one allylic position remains essentially unchanged. It is re-

ported that 1-carbethoxycyclohexene is brominated in the 3-position

rather than the 6-position, with N-bromosuccimide and benzoyl
42
peroxide. If aziridine 94 can be synthesized, allylic bromin-

ation may occur at the most active allylic position.




COOEt








94







The synthesis of 94 began with the isolation of 95 in 74% yield,

Scheme LXXVII, from the reaction of 11, 12-dimethylene-9, 10-etheno-

9, 10-dihydroanthracene (84) and ethyl propiolate. The nmr spectrum




- 68 -


Scheme LXXVII


94 + HC=C COOEt


of 25 showed no proton absorption in the vinyl region as expected.

The bridgehead protons appeared as two close singlets at 4.72 and

4.77. R-Methoxyphenyl azide (70) was then added to 95. The expected

triazoline isomers96 and 97 were shown to be present based on an nmr





CEOOEt -O- Me
EtOOC,_,_, vOMe -,4,


97


96




- 69 -


spectrum of the reaction mixture. The bridge protons region

changed from two singlets to a complex multiple. The methoxy

protons were also present in addition to some residual azide.

There was strong absorption in the vinyl region, suggestive of

bridgehead protons on triptycene derivatives. Since the triazoline

isomers give the same aziridine 94, photolysis of the reaction

mixture with subsequent separation by column chromatography was





COOEt








94





pursued. The desired product 94 was not obtained. Only the tripty-

cene derivative 98 and residual starting materials were isolated.

Characterization of 98 was accomplished by nmr and high resolution

mass spectroscopy. The product isolated from the reaction of 95

with NBS, Scheme LXVIII, showed identical spectral properties to 48.

A number of diene systems have been shown to aromatize with NBS.43
A number of diene systems have been shown to aromatize with NBS.




- 70 -


Scheme LXXVIII








COOEt COOEt



M NBS
Q O C C14
^ Bz202

95 98







An attempt was then made to add the azide 70 to anhydride 79.

If the triazoline 29 could have been formed and subsequent photolysis

gave the aziridine 100, oxidative or electrolytic bisdecarboxylation

might give the desired unsaturated aziridine 101, Scheme LXXIX.

Anhydride 79 and azide 70 were heated at 100C in a Carius tube for

seven days. Triazoline 99 was present according to nmr spectro-

scopy. The spectrum of the triazoline showed the methoxy protons

at 3.77 and two singlets for the bridgehead protons. Purification

and further characterization was quite difficult. Photolysis of the




- 71 -


Scheme LXXIX





N3

+ 0 1 A
OMe

70


99


, M e


hv


Elect.


100


crude triazoline 99 was successful as depicted by nmr spectroscopy,
but purification problems were again encountered. The separation of
the aziridine 100 from other components of the mixture was achieved
in a crude form by fractional crystallization. Hydrolysis of the




- 72 -


anhydride 100 was also noted during recrystallization. In order to

eliminate these problems, the diacid 80 was converted to diester

102, Scheme LXXX, in 91% yield. The diester 102 was treated with

Scheme LXXX


MeOO'


H H
MeOH


80


102


R-methoxyphenyl azide (70) in a Carius tube at 100 0C for four days,

Scheme LXXXI. Although other products were formed, the triazoline




- 73 -


Scheme LXXXI








COOMe O
N3 MeOOC a O3

102 + W EOAc 4

0 Me

70
-103













could be separated in good yield using column chromatography. It

was later found that a decrease in temperature from 100 0C to 80 0C,

and an increase in reaction time from four to seven days, increased

the yield of triazoline 103 and decreased the by-products previously

observed. Column chromatography was not required for isolation of

the triazoline. The triazoline 103 was then photolized to give the




- 74 -


desired aziridine 104 in 93% yield, Scheme LXXXII. The aziridine
Scheme LXXXII


Me004


103


vOrMe


hv
Acetone


104


was characterized by mass spectral analysis and its nmr spectrum

showed close similarity to 91.

Saponification of 104_ was finally accomplished, Scheme LXXXIII,

Scheme LXXXIII



COONa
NaOOy< K^sOMe

104 NaOH NaOOOMe
Diglyme


105





- 75 -


by the reaction of 10% sodium hydroxide in aqueous diglyme solution.

Infrared spectroscopy supported the disodium salt structure 105.

Further characterization of the salt 105 was difficult due to its

solubility properties and acid sensitive functions. Attempts were

made to esterify the disodium salt 105 by acidification at low

temperature with 5% perchloric acid, Scheme LXXXIV. Aziridines

Scheme LXXXIV


105


HC104 c
OOC


106










have been shown to be stable under these conditions. Esterification

of the diacid 106 with diazomethane gave a mixture of products

but not the expected diester 104, Scheme LXXXV. Ring opening





- 76 -


Scheme LXXXV


MeOOI


CH2N2 .
Et2 //


prior to the esterification would probably have justified these results.

Electrolytic bisdecarboxylation of the disodium salt 105, Scheme

LXXXVI, also resulted in a complex mixture. The desired diene 101

Scheme LXXXVI





Elect. _OM e

105 E c .


I01


106


104





- 77 -


was not obtained. These results could be attributed to the aziridine

being unstable under electrolytic conditions.


SUMMARY AND CONCLUSIONS

Diene 58 was chosen because it would have a minimum number of

functional groups after the azide addition, but attempted synthesis

resulted in aromatization to triptycene. Stabilization of diene 86

and 95 with ester groups was successful. Azide addition to diene

86 and subsequent photolysis of the resulting triazoline 87 gave

the desired aziridine 91. Azide addition of 95 resulted in aroma-

tization to the triptycene derivative 98. Aromatic substitution oc-

curred on allylic bromination of 9J.. Purification problems of azide

addition to the anhydride 79 were eliminated by converting the an-

hydride to the diester 102. Addition of the azide and subsequent

photolysis gave the aziridine 104. Saponification of 104 followed

by bisdecarboxylation of the disodium salt resulted in a complex

mixture. It is suggested that an aziridine such as 107 be synthe-

sized with a deactivated phenyl or alkyl as the R group. If the X

groups are removable by base, the diene 51 might be synthesized.


107














CHAPTER III


EXPERIMENTAL


General

Melting points were determined on a Thomas-Hoover Unimelt

Capillary melting point apparatus and are uncorrected.

Infrared spectra were recorded on a Perkin-Elmer 137 or Beck-

mann IR-IO spectrophotometer with absorptions reported in recipro-
-l
cal centimeters (cm ). All nuclear magnetic resonance spectra

(nmr) were obtained on a Varian A60-A spectrometer. Chemical

shifts of nmnr spectra run in organic solvents are reported in

ppmfW) downfield from internal standard tetramethylsilane. Low

resolution mass spectra were determined on a Hitachi model RMU-6E

mass spectrometer. High resolution accurate mass spectra were

determined on a AEI MS-30 double beam mass spectrometer. Micro-

analyses were obtained from Atlanta Microlab, Inc., Atlanta,

Georgia.

Separation by column chromatography was conducted using Fisher

Adsorption alumina (A-540, 80-200 mesh and Baker Silica Gel). De-

activated alumina were prepared by adding the desired amount of


- 78 -




- 79 -


water (by weight percent) to the alumina and shaking until no lumps

were visible. Silca gel was used directly and with no previous

treatment. Solvent evaporations were carried out using a Buchler

rotary evaporator in vacuo (water aspirator) and by using a Buchi

Rotaryvapor-R in vacuo (pumps).

Ethyl a-hydroxy-a-(9-fluorenyl acetate) (22)

Zinc metal (19.6 g., 0.300 g. atom) was placed in dried 1-liter

three-necked flask equipped with a dropping funnel, condenser, and

a mechanical stirrer. Fluorenone (50.0 g., 0.259 mole) and ethyl

bromoacetate (45.0 g., 0.269 mole) were added to the dropping funnel,

approximately one-third of the solution added and heated to reflux.

A few crystals of iodine were added to initiate the reaction and the

addition was continued at a rate to maintain reflux. After refluxing

for an additional hour, the reaction was terminated, cooled and poured

into cold 10% sulfuric acid. The benzene layer was separated, washed

with water and 5% sodium bicarbonate. The aqueous solution was ex-

tracted twice with benzene, the benzene layer washed with water,

5% sodium bicarbonate and combined with the first extract. The

solution was dried over anhydrous magnesium sulfate, filtered and

used directly in the next step. A small sample was taken for spectral
-I -l
determination; ir (neat) cm 3320 (OH); 1730 cm (C= 0, ester);

nmr (DCC13); 0.97 (t, 3, J = 7 Hz); 2.80 (s, 2); 3.95 (q, 2, J = 7 Hz);-,

4.22 (broad 5, 1); 7.28 7.58 (m, 8).




- 80 -


Ethyl fluorenylidene acetate ( )10

Toluensulfonic acid (1.00 g.) was added to the benzene solution

and refluxed until 4.6 ml. of water was collected (Dean-Stark trap).

The reaction was allowed to cool to room temperature and then evapor-

ated to a yellow solid. The yellow solid was crystallized from

ethanol (95%) to give ethyl fluorenylidene acetate (63.3 g., 91%)

long yellow needles; mp.76-77 C.

Ethyl azidoformate

The title compound was prepared according to the published pro-

44
cedure of Forster and Fierz.

Attempted synthesis of 1,2-dicarbothoxy-3-spiro-(9-fluorenyl) aziridine

Ethyl fluorenylideneacetate (1.00 g., 4.0 mmole) was dissolved

in methylene chloride. Ethyl azidoformate (0.559 g., 0.0049 mole)

was added, and the infrared spectrum taken. The reaction was allowed

to stand at room temperature. Infrared spectrum was taken after one

month, three months, six months, and one year but showed no change.

Only starting materials were recovered as determined by infrared and

nmr spectroscopy.

Ethyl a-bromo--(9-bromofluorenyl) acetate (24)

The title compound was prepared according to the procedure of

Gilchrist and Rees. i1




- 81 -


Reaction of ethyl a-bromo-a-(9-bromofluorenyl) acetate with ammonia

Ethyl a-bromo-ca-(9-bromofluorenyl) acetate (1.00 g., 2.44 mmoles)

was dissolved in 5 ml. of absolute ethanol. Concentrated aqueous

ammonia (5 ml.) was added and the reaction stirred for eight hours.

Distilled water (25 ml.) was then added, the resultant solution

extracted with ether and dried over anhydrous magnesium sulfate.

Filtration and evaporation gave a product identical in spectral

properties to that of a-bromofluorenylideneacetate as prepared by

Gilchrist and Rees.

-Bromofluorenylideneacetate (25)

The title compound was prepared according to the procedure of
11
Gilchrist and Rees.

Attempted reaction of a-bromofluorenylideneacetate with ammonia

cz-bromofluorenylideneacetate (100 mg., 0.304 mmole) was dissolved

in 6 ml. of absolute ethanol. Concentrated aqueous ammonia (10 ml.)

was added and the reaction stirred at room temperature for 5 days.

Distilled water (10 ml.) was added and the resultant solution extracted

with ether. The ether extract was dried over anhydrous magnesium

sulfate. Filtration and evaporation gave only starting material as

determined by nmr spectoscopy.

Ethyl a-bromo-a-(9-isocyanatofluorenyl) acetate (26)

Ethyl a-bromo-ca-(9-bromnofluorenyl) acetate (5.00 g., 0.0122 mole)

was dissolved in 100 ml. of anhydrous diethyl ether. Freshly prepared





- 82 -


4 5
silver cyanate45 (2.00 g., 0.0133 mole) was then added and the re-

action mixture stirred for twenty-four hours at room temperature.

The reaction mixture was filtered through Celite 540 to give a

yellow solution which was evaporated to dryness to give a deep
-l
yellow oil. (3.80 g., 83.7%); ir (neat) cm1 2247 (N = C = 0).

Ethyl-a-bromo-c-(9-carbethoxyaminofluorenyl) acetate (2B)

Ethyl o-bromo-Q-(9-isocyanatofluorenyl) acetate (3.72 g., 0.01

mole) was warmed with absolute ethanol and allowed to cool. The

white solid was filtered and recrystallized from ethanol (95%)

giving ethyl a-bromo-a-(9-carbethoxyaminofluorenyl) acetate: (3.96 g.,
0 -1
98%); mp. 112-114C; ir (K B2) cm 3300 (N-H); 1740 (C = 0); 1680

(C = 0); nmr (CC14)W 0.98 (q, 6, J = 8 Hz); 3.87 (q, 4, 5 = 8 Hz);

4.92 (s, 1); 5.90 (broad) (s, 1); 7.07-7.97 (m, 7).

Anal. Calcd for C20 H20 NO4 B C; 57.43; H, 4.82; N, 3.35
Found = C; 57.46; H, 4.85; N, 3.35

Ethyl-[2-ethoxy-5-spiro-(9-fluorenyl)-oxazoline] acetate (31)

Absolute ethanol (50 ml.) was placed in a 100-ml. dry round-

bottomed flask equipped with a reflux condenser and magnetic stirrer.

Sodium (0.090 g., 0.00391 g. atoms) was added and the reaction

mixture was allowed to stir at room temperature until all the sodium

had reacted. Ethyl a-bromo-a-(9-carbethoxyaminofluorenyl) acetate

(1.25 g., 0.00299 mole) was added and refluxed for six and one-half

hours. The resultant orange solution was evaporated to dryness,




- 83 -


water added, and extracted with ether. The ether extract was washed

with 10% sodium bicarbonate and dried over anhydrous magnesium sul-

fate. The ether extract was filtered and evaporated to give a deep

yellow oil. Recrystallization from petroleum ether (60-110) gave

colorless crystals of Ethyl-[2-ethoxy-(4-fluorenyl)-oxazoline] acetate

(0.806 g., 80%): mp.-88-90C; ir (KBr) cm- 1740 (C = 0); 1660 (C=N);

nmr (CCI4) )f 0.55 (t,3, J=6 Hz); 1.28 (t,3, J=6 Hz); 3.57 (q,2, J=6 Hz)-,

4.27 (q,2, J=6 Hz); 5.07 (s,l); 7.15-7.60 (m,8); mass spectrum; Found:

m/e 337.1329 (calcd. for C20H1904N: m/e 337.1313Y.

4-Carbethoxy-5-spiro-(9-fluorenyl )-2-oxazolidone (32)

Ethyl ca-bromo-c-(9-carbethoxyaminofluorenyl) acetate (1.02 g.,

0.00236 mole) was heated in a sealed tube at 200C for ten minutes.

The sample was cooled and recrystallized from benzene to give color-

less crystals of 4-carbethoxy-5-spiro-(9-fluorenyl)-2-oxazolidone

(0.757 g., 100%):mp.219-220C; ir (KBr) cm"1 3240(N-H) i1770 (C=O),

1750 (C=O); nmr (D6 MSO) f 0.60 (t,3,5 = 7Hz); 3.10 (broad s,l);

3.63 (q,2,J=7Hz); 5.37 (5,1); 7.28-7.90 (m,8).

m/e (calculated for C18H15 04N) = 309.1000

Found = 309.1042
Reaction of Ethyl -[2-ethoxy-5-spiro-(9-fluorenyl)-oxazoline acetate
with hydrobromic acid

Ethyl-[2-ethoxy-5-spiro-(9-fluorenyl)-oxazoline] acetate (60 mg.,

0.178 mmole) was added to diethyl ether (20 ml.) previously saturated





- 84 -


with HBr. The reaction was allowed to stir at room temperature for

one hour. Evaporation and recrystallization from benzene gave a

product (45 mg., 82%) showing identical physical and spectral pro-

perties to those of 4-carbethoxy-5-spiro-(9-f I uorenyl )-2oxazol done.

4-Methyl-5-spiro-(9-fluorenyl )-2-oxazol idone (36)

Ethyl-Gc-bromo-Q-(9-carbethoxyami nofluorenyl) acetate (1.00 g.,

2.39 mmoles) was refluxed for two and one-half hours in alcoholic

potassium hydroxide (5.0 g. in 50 ml. of 95% ethanol). The reaction

mixture was allowed to cool to room temperature and evaporated to

dryness. Water was then added and extracted with ether. The ether

layer was washed with water and dried over anhydrous magnesium sul-

fate. Filtration and removal of solvent (rotary evaporator) gave a

light yellow residue. Recrystallization from benzene and petroleum

ether (80-110 C) gave 4-methyl-5-spiro-(9-fluorenyl)-2-oxazolidone
o -l
(0.220 g., 37%) white crystals; mp. 160-161C. ir (KBr) cm 3325

(N-H; broad); 1735 (C=O, strong), nmr (DCCI ) c6 0.93 (d,3,J=7Hz);

4.98 (q,l,J=7Hz); 5.42 (s,l,broad); 7.27-7.73 (m,8);

m/e (calculated for C16H13 02N) = 251.0945

Found = 251.0926

9-Ami nof uorene (LOP)

9-Amninofluorene hydroxychloride (2.00 g., 9.22 mmoles) was

dissolved in 100 ml. of distilled water. Sodium hydroxide (15%)




- 85 -


was added until the solution was basic and then an additional 15 ml.

excess was added. A white precipitate formed and was extracted with

diethyl ether (150 ml.; 3 x 50 ml.). The ether extract was washed

twice with water and dried over anhydrous magnesium sulfate. After

filtering, evaporation of solvent gave 9-amino-fluorene (1.60 g., 96%)

a bright yellow solid; mp. 121 C. nmr (DCC1 ) c3 1.68(s,2); 4.72

(s,l); 7.15-7.83 (m,8).

9-Carbethoxyimni nof I uorene

This compound was prepared according to the method of Deyrup and
46
Gill. Into a 250-ml. round-bottomed flask equipped with a magnetic

stirrer, Dean-Stark trap and a reflux condenser was placed activated
47l
manganese dioxide (1.38 g., 0.0158 mole) in 100 ml. of benzene. The

mixture was refluxed for 12 hours. 9--Carbethoxyaminofluorene (0.500 g.,

0.00198 mole) was then added and the reaction mixture was then allowed

to cool to room temperature, filtered through Celite-545. The yellow

solution was evaporated to dryness to give a yellow oil. Re-

crystallization from petroleum ether (60-110) gave 9-carbethoxy-

iminofluorene (0.200 g., 40%) a bright yellow solid; mp. 70-72 C.
-1
ir (KBr) cmr 1700 (C=O); 1680 (C=N),

nmr (CC]4) cf 1.40 (t,3,5=7Hz); 4.37 (q,2,J=7Hz); 6.95-7.66 (m,8).

m/e (calculated for C16H13NO2) = 251.0945

Found = 251.0956





- 86 -


9-Carbethoxyaminofluorene (4W)

The title compound was prepared according to the procedure of

Neish.17

9-Carbethoxyiminofluorene (3J)

Fluorenylideneimine (0.500 g., 0.00279 mole) was dissolved in

dry benzene and triethyl amine (1.00 ml.) added. Ethyl chloroformate

(0.303 g., 0.00279 mole) was added slowly and the reaction stirred

at room temperature for twenty-four hours. The reaction was then

filtered and evaporated to dryness. Recrystallization from benzene

and petroleum ether (20-40) gave 9-carbethoxyiminofluorene (0.376, 54%)

of yellow crystals; mp. 70-71. Spectral properties were the same as

those synthesized in the first part.

Fluorenylideneimine (42)

The title compound was prepared by the procedure of Harris,

Harriman and Wheeler.48

Methyl c-bromo-o-(9-carbethoxyaminofluorenyl) acetate (29)

The title compound was prepared by the same procedure as ethyl

ca-bromo-&-(9-carbethoxyaminofluorenyl) acetate: mp. 127-128.5 C.
-1
ir (KBr) cm1 3300 (N-H); 1740 (C=O); 1690 (C=O);

nmr (CC4) cr 0.98 (t,3,J=7Hz); 3.50 (s,3); 3.92 (q,2,J=7Hz);

4.93 (s,l); 6.00 (s,l, broad); 7.17-7.97 (m,8).




- 87 -


Reaction of Methyl C-bromo-o-(9-carbethoxyaminofluorenyl) acetate
with alcoholic potassium hydroxide

Methyl o-bromno-a-(9-carbethoxyaminofluorenyl acetate was

treated under the same conditions and its ethyl derivative. Only

9-fluorenone, in 20% yield, was isolated from the reaction.

Reaction of 9-Carbethoxyiminofluorene with alcoholic potassium
hydroxide

9-Carbethoxyiminofluorene (0.200 g., 0.000797 mole) was added

to alcoholic solution (1.00 g., KOH in 10 ml. of 95% ethanol) and

refluxed for two and one-half hours. On cooling, the brown mixture

was evaporated to dryness, water added and extracted with ether.

The ether extract was washed with water and dried over anhydrous

magnesium sulfate. Filtration and removal of solvent left a deep

yellow oil. The nmr spectrum of this material was identical to

that of 9-fluorenone.

Attempted Reaction of 9-Carbethoxyiminofluorene with Benzoyl Peroxide

9-Carbethoxyiminofluorene (50 mg., 0.0199 mmole) and a catalytic

amount of benzoyl peroxide were added to a dry 25 ml. round-bottomed

flask equipped with a reflux condenser and a drying tube. The

apparatus was flushed with nitrogen and chlorobenzene (5 ml.) added.

The reaction was refluxed for two and one-half hours, cooled, and

evaporated. Only starting material was isolated from the reaction.




- 88 -


Attempted Reaction of 9-Carbethoxyiminofluorene with Ditertbutyl
Peroxide

9-Carbethoxyiminofluorene (50 mg., 0.199 mmole), chlorobenzene

(5.0 ml.) and tert-butyl peroxide (1.0 ml.) was placed in a Carius

tube and heated at 100 0C for thirty hours. The solution was cooled

and evaporated to give a yellow. residue. Only starting material

was isolated as determined by rnr spectroscopy.

Ethyl a-bromo-a-(9-aminofluorenyl) acetate (4)

Ethyl Q-bromo-a-(9-isocyanatofluorenyl) acetate (3.83 g.,

0.0129 mole) was dissolved in 25 ml. of acetone and 20 ml. of hydro-

iodic acid (48%) was added. The solution was allowed to stir for

four hours at room temperature. The dark solution was extracted

first with ether. The aqueous layer was made basic with 10% sodium

hydroxide and extracted three times with ether. On drying (anhydrous

magnesium sulfate), filtering and evaporating gave a light yellow oil

of ethyl a-bromo-a-(9-aminofluorenyl) acetate (2.57 g., 72%).
-l
ir (neat) cm1 3400 (N-H); 1720 (C=O);

nmr (CCI4) c 0.95 (t,3,J=7Hz); 2.25 (s,2); 3.92 (q,2,J=7Hz);

4.48 (s,l); 7.08-7.87 (m,8).

Ethyl 2-spiro-(9-fluorenyl) aziridine carboxylate (L0)

Ethyl a-bromo-o-(9-aminofluorenyl) acetate (5.85 g., 0.0169 mole)

was dissolved in 25 ml. of absolute ethanol. Triethyl amine (25 ml.)

was added and the reaction stirred at room temperature for three days.




- 89 -


The reaction mixture was evaporated to dryness to give a light yellow

solid. Water was then added and the aqueous mixture extracted with

ether. The ether extract was washed once with water and dried over

anhydrous magnesium sulfate. After filtering and removal of solvent

the residue, a light yellow oil, was recrystallized from 95% ethanol

to give white crystals of 2-carbethoxy-3-spiro-(9-fluorenyl) aziridine

(4.40 g., 98%); mp. 118-120C; ir (KBr) cm-1 3448 (N-H); 1739 (C=0);

nmr (DCCI3 ) c 1.08 (t,3,J=7Hz); 2.58 (broad) (d,l,J=9Hz); 3.43 (broad)

(d,l,J=9Hz); 4.13 (q,2,J=7Hz); 7.00-7.77 (m,8).

Anal. Calcd for C7 H 5NO : C, 76.96; H, 5.70; N, 5.28

Found: C, 76.82; H, 5.77; N, 5.25

Sodium 2-spiro-(9-fluorenyl)-aziridinecarboxylate (O6)

Ethyl 2-spiro-(9-fluorenyl)-aziridinecarboxylate (2.00 g.,

0.00755 moles) was dissolved in 50 ml. of 95% ethanol and sodium

hydroxide (8.0 ml. of 1.0 M, 0.0080 mole) was added. The reaction

was allowed to stir for one hour in which the salt precipitate, the

white solid was filtered, washed with ether and dried under vacuum

to give sodium 2-spiro-(9-fluorenyl)-aziridinecarboxylate (1.96 g.,

100%) as a white powder. A small amount of the sodium salt was re-

crystallized from water (mp. 154-156 decomposition turning red),

which was identified by spectral properties.




- 90 -


Reaction ot Sodium 2-spiro-(9-fluorenyl) aziridine carboxylate
with Thionyl Chloride (Attempted)

This procedure was patterned after that of Deyrup and Clough.

Into a dried three-necked flask equipped with a magnetic

stirrer, inlet and outlet tubes for a nitrogen atmosphere, and

a rubber septrum was added a 57% sodium hydride suspension (0.509 g.,

0.012 mole). The sodium hydride was washed three times and dry

tetrahydrofuran (10 ml.) was added to the reaction flask. Sodium

2-spiro-(9-fluorenyl)-aziridinecarboxylate (0.266 g., 0.0010 mole)

was added and then thionyl chloride (0.071 ml., 0.0010 mole). The

reaction turned yellow immediately and was stirred at room temper-

ature for one hour and twenty-five minutes. The reaction mixture

was filtered through Celite 540 and evaporated to give deep yellow

residue. Analysis of this residue by nmr showed no desired products

had been formed.

Anthracene-9, 10-endo-a, .P-succinic anhydride (5)

The title compound was prepared according to the procedure
49
of Bachmann and Kloetzel.

Disodium 9, 10-endo-c, p-succinate (L7)

Anthracene 9, 10-endo-a, P-succinic anhydride (2.09 g., 0.075

mole) and sodium hydroxide (4.0 g., 0.1 mole) was dissolved in 50%

ethanol and refluxed for two hours. The solution was cooled, evapor-

ated and then dried under vacuum to give a quantitative yield of di-




- 91 -


sodium 9, 10-endo-a, 3-succinate. The product was identified by ir

and nmr spectroscopy.

Anthracene-9, 10-endo-a, P-succinic acid (68)

Anthracene-9, 10-endo-a, p-succinic anhydride (5.00 g., 0.0181

mole) was refluxed in water (100 ml.) for two hours. White crystals

precipitated as the solution cooled. After filtration and drying

anthracene-9, 10-endo-a, p-succinic acid (4.92 g., 99%) was obtained.



Electrolytic Bisdecarboxylation (General Method)

The electrolysis was carried out by a procedure similar to that

50 51 52 53
used by Corey Plieninger Sims and Whitesides52 and Dauben53

The electrolysis apparatus was constructed from a 200 ml. tall-

form beaker that was water-jacketed, two electrodes of platinum gauze

and a mechanical stirrer. The coolant, water, circulated through

the reaction jacket through a copper coil immersed in an ice bath.

The temperature was maintained automatically at 20 C with a control

device composed of a thermometer, immersed into the constructed cell,

a relay and peristalic pump. A mechanical stirrer rotated the

cylindrical platinum gauze anode inside the cylindrical cathode,

both of which were inside the 200 ml. reaction vessel. A volta-

meter and ampmeter were added to the circuit to monitor the electrol-

ysis. Power was supplied by a Lambda (Model LA 20-05 BM-505) con-