• TABLE OF CONTENTS
HIDE
 Title Page
 Dedication
 Table of Contents
 Acknowledgement
 List of Tables
 Abstract
 Reactions of t-Butyl Isonitril...
 Evidence for the structure and...
 4, 5-Dinohydro-1H-1, 4-benzodiazepines...
 5-Imino-2-oxo-1, 2, 3-oxathiazolidines...
 Experimental
 Appendix
 Bibliography
 Biographical sketch














Title: Hetero-syntheses with isocyanides, by James C. Gill
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 Material Information
Title: Hetero-syntheses with isocyanides, by James C. Gill
Physical Description: xi, 227 leaves. : ; 28 cm.
Language: English
Creator: Gill, James Charles, 1944-
Publication Date: 1972
Copyright Date: 1972
 Subjects
Subject: Isocyanides   ( lcsh )
Chemistry thesis Ph. D
Dissertations, Academic -- Chemistry -- UF
Genre: bibliography   ( marcgt )
non-fiction   ( marcgt )
 Notes
Thesis: Thesis -- University of Florida.
Bibliography: Bibliography: leaves 217-226.
General Note: Typescript.
General Note: Vita.
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Bibliographic ID: UF00099537
Volume ID: VID00001
Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: All rights reserved by the source institution and holding location.
Resource Identifier: alephbibnum - 000577287
oclc - 13956255
notis - ADA4982

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Table of Contents
    Title Page
        Page i
        Page ii
    Dedication
        Page iii
    Table of Contents
        Page v
        Page vi
        Page vii
        Page viii
    Acknowledgement
        Page iv
    List of Tables
        Page ix
    Abstract
        Page x
        Page xi
    Reactions of t-Butyl Isonitrile
        Page 1
        Page 2
        Page 3
        Page 4
        Page 5
        Page 6
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    Evidence for the structure and conformation of conjugated drimines
        Page 52
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    4, 5-Dinohydro-1H-1, 4-benzodiazepines (118)
        Page 99
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        Page 126
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    5-Imino-2-oxo-1, 2, 3-oxathiazolidines (160)
        Page 128
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    Experimental
        Page 142
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    Appendix
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    Bibliography
        Page 217
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    Biographical sketch
        Page 227
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Full Text













HETERO-SYNTHESES WITH ISOCYANIDES


By



JAMES C. GILL












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
1972


































Copyright by

James C. Gill

1972
































It is with great pleasure, the author proudly dedicates

this dissertation to his parents and brother whose unselfish

sacrifices, experience, and encouragement helped make this

goal a reality.














TABLE OF CONTENTS


Page

ACKNOWLEDGEMENTS...................................... iv

LIST OF TABLES........................................ ix

ABSTRACT.............................................. x

CHAPTER I Reactions of t-Butyl Isonitrile............ 1

Introduction .... ............................ 1
Discussion................................... 7
Conclusions with Comments for Further
Research ....................... .......... 42

II Evidence for the Structure and Conformation
Conjugated Diimines.................. ...... 52

Introduction. .............................. 52
Discussion................................... 53
Conclusion ........................... .... .. 92

III 4,5-Dihydro-lH-l,4-benzodiazepines (118)... 99

Introduction............................... 99
Discussion.................................. 107
Conclusion ................................. 123

IV 5-Imino-2-oxo-l,2,3-oxathiazolidines (160). 128

Introduction............................... 128
Discussion .............................. 130
Conclusion ................................. 140

V Experimental ............................... 142

t-Butyl Isonitrile (5) ..................... 143
p-Nitrobenzylidene-t-butylamine (18a) ....... 143
Reaction of p-Nitrobenzylidene-t-butylamine
(18a) with t-Butyl Isonitrile............ 143
a-Cyano-4-Nitrophenylglyoxylidenedi-t-butyl-
amine (20a)............................... 146
l-t-Butyl-5-cyano-4-(4-nitrophenyl)imidazole
21a) .................................... 146









Table of Contents (continued)


Page

a-(N-t-Butylacetamidc)-B-t-butylanino-4-
nitrocinnamonitrile (26a ) ............... 147
General Procedure for the Preparation of
p-Nitrobenzylidene-2,6-dialkylaniline... 148
Reaction of p-Nitrobenzylidene-2,6-di-
methylaniline (18b) with t-Butyl
Isonitrile .............................. 148
a-Cyano-4-nitrophenylglyoxylidene-a-(t-
butylamine)-B-(2,6-dimethylaniline)
(20b) ................................. 150
1-(2,6-Dimethylphenyl)-4-cyano-5-(4-nitro-
phenyl)imidazole (22b) .................. 151
The Attempted 1,4-Cycloaddition of a-Cyano-
4-nitrophenylglyoxylidene-a-(t-butylamine)-
S-(2,6-dimethylaniline) (20b) with p-
Benzoquinone............................... 152
The Attempted 1,4-Cycloaddition of a-Cyano-
4-nitrophenylglyoxylidene-a-(t-butyl-
amine)-B-(2,6-dimethylanilineT (20b)
with Ketene Diethylacetal. The Prepara-
tion of 4-t-Butyl-3-cyano-4,5-dihydro-9-
methyl-2-(4-nitrophenyl)-1H-1,4-benzo-
diazepine (35) .......................... 152
4-t-Butyl-4,5-dihydro-9-methyl-2-(4-nitro-
phenyl)-3H-1,4-benzodiazepin-3-one (39). 153
p-Nitrobenzylidenemethylamine (18c)....... 153
Reaction of p-Nitrobenzylidenemethylamine
(18c) with t-Butyl Isonitrile............ 153
a-Cyano-4-nitrophenylglyoxylidene-a-(t-
butylamine)-6-(methylamine) (20c)....... 154
4-Cyano-l-methyl-5-(4-nitrophenyl)imidazole
(22c) and l-t-butyl-5-cyano-4-(4-nitro-
phenyl)imidazole (21a).................. 155
4-Cyano-1,2-dimethyl-5-(4-nitrophenyl)-
imidazole (27c)......................... 156
p-Nitrobenzylidenebenzylamine (18d)....... 157
Reaction of p-Nitrobenzylidenebenzylamine
(18d) with t-Butyl Isonitrile............ 157
p-Nitrophenylglyoxal Hydrate (22)......... 159
p-Nitrophenylglyoxylidene-a-t-butylamine
(23) ...................... ............. 159
p-Nitrophenylglyoxylidenedi-t-butylamine
(24a) .......... .... ................... 160
a,B-Di-t-butylamino-4-nitrocinnamonitrile
(19aT .................................. 161
Phenylgloxal Hydrate (63) ................. 162
Phenylglyoxylidene-a-t-butylamine4 (64).. 162
Phenylglyoxylidene-a, -di-t-butylamin -(65) 162









Table of Contents (continued)


Page

a-Cyano-phenylglyoxylidenedi-t-butyl-
amine (68) ............................ 162
4-Nitrophenylglyoxylidene-bis(2,6-dimethyl-
aniline) (144).......................... 163
a-Cyano-4-nitrophenylglyoxylidene-c,8-bis-
(2,6-dimethylaniline (107) .............. 164
Benzilylidene-di-t-butylammne (93) ........ 165
4,5-Diphenylglyoxalone .................... 166
4,4'-Dinitrobenzil....... .................. 166
4,4'-Dinitrobenzilylidenedi-t-butylamine
(94) .............. ...................... 166
Benzophenone-t-butylimine (84)............. 167
p-Nitroacetophenone-t-butylimine.......... 167
Phenanthrenequinonedi-t-butylimine (95)... 168
Glyoxylidenedi-t-butylamine (82).......... 169
Reaction of Glyoxylidenedi-t-butylamine
with Acetone Cyanohydrin................ 169
c-Cyanoglyoxylidenedi-t-butylamine (87)... 170
1,2-Di-t-butylamino-l,2-dicyanoethylene... 171
a,B-Dicyanoglyoxylidenedi-t-butylamine.... 172
Glyoxylidenedi-o-toluidine (148).......... 172
2,3-Di-o-toluidinoacrylonitrile (149)...... 173
a-Cyanoglyoxylidenedi-o-toluidine- 09)... 174
a, -Dicyanoglyoxylidenedi-o-toluidine (109) 174
Benzylideneaniline.... .................. 175
2-Anilino-2-phenylacetonitrile (110)...... 176
N-Phenylbenzimidyl Cyanide (111) .......... 176
N-t-Butyl-N'-o-tolylethylenediamine (165). 177
Glyoxylidene-t-butylamine-o-toluidine
(166) .................. ................ 178
N-t-Butyl-2-chloro-2-phenylacetamide (172) 178
N-t-Butyl-2-(N'-o-tolyl)-2-phenylacetamide
T173)........ ............................. 179
1-N-t-butyl-2-(N'o-tolyl)-2-phenylethyl-
enediamine (174 ......................... 180
Reaction of l-N-t-Butyl-2-(N'-o-tolyl)-2-
phenylethylenediamine (174) with Acti-
vated Manganese Dioxide.... ............ 181
General Procedure for Preparation of
1H-1,4-Benzodiazepines .................. 181
2-Chloroacetamides........................ 182
2-Chloroacet-o-toluidide.................. 182
General Procedure for Preparation of
2-Aminoacetamides........................ 184
General Procedure for Preparation of 5-
Imino-2-oxo-1,2,3-oxathiazolidines (195) 184
Reaction of a-Cyano-4-nitrophenylglyoxyl--
denedi-t-butylamine (20a) with m-Chloro-
perbenzoic Acid......................... 185









Table of Contents (continued)


Page

APPENDIX.............................................. 189

BIBLIOGRAPHY AND NOTES................................. 217

BIOGRAPHICAL SKETCH................................. .. 227


viii














ACKNOWLEDGMENTS


The author wishes to express his deepest appreciation to

his Chairman, Dr. James A. Deyrup, whose guidance, encour-

agement, criticism, and ideas during the execution of this

research program were of unestimable value. Although there

were good and bad times he will always think of his Chairman

as not only a research director but as a friend.

The author wishes to thank the faculty and staff of

the University of Florida, his Supervisory Committee, and

fellow graduate students for their aid and guidance during

his stay. Special thanks are due to Mr. Carl Strohmenger

for his generous technical assistance.

The author also thanks Mrs. Judi G. Nielsen for her

patience and endurance in typing this dissertation and to

Mr. William A. Szabo for his generous help with the drawings

in the dissertation.

Last, but not least, the author wishes to thank his

parents for their support, encouragement and advice through-

out the course of his college education.














LIST OF TABLES


Table Page

I Preliminary Reactions............................ 8

II Variations on Experiment F..................... 9

III Chemical Shifts of H-4 and H-6.................. 41

IV NMR Spectra of the Diimines.................... 95

V Optimization Reaction for 35.................... 109

VI Reaction Parameters for the Preparation of
1H-1,4-Benzodiazepines......................... 125

VII Spectral Properties of 2-Aminoacetamides........ 133

VIII Spectral Properties of 5-Imino-2-oxo-l,2,3-
oxathiazolidines............................... 135

IX Physical Parameters for Several p-Nitrobenzyli-
dene-2,6-dialkylanilines ...................... 149

X Physical Parameters for 2-Chloroacetamides..... 183

XI Physical Parameters for 2-Aminoacetamides...... 186

XII Physical Parameters for 5-Imino-l,2,3-oxathiazo-
lidines....................................... 187









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



HETERO-SYNTHESES WITH ISOCYANIDES

By

James C. Gill

December, 1972

Chairman: James A. Deyrup
Major Department: Chemistry

As part of the continued study of the reactions of

t-butyl isonitrile, it was found that two equivalents of

t-butyl isonitrile added in the presence of an acid catalyst

to 2-nitrobenzylidenealkyl- or arylamines which lacked aryl

electrons available for cyclization. The product was assigned

the structure of an a,6-diamino-p-nitrocinnamonitrile deri-

vative based on spectral evidence and analytical data as

well as an independent synthesis. The a,S-diamino-p-nitro-

cinnamonitrile derivatives were found to be useful precursors

to diimines, and heterocyclic rings difficultly obtained by

other synthetic methods.

In order to unequivocally determine the structures of

the diimines prepared from the a,8-diamino-p-nitrocinnamo-

nitrile derivatives, other diimines were prepared by alter-

native routes. Each of these compounds displayed a tempera-

ture dependent nmr spectrum which was explained in terms of

an equilibrium of two conformations. The "normal" nmr

pattern was explained in terms of a completely planar









Z-s-trans-E conformer and the "abnormal" nmr pattern was

explained in terms of a planar E-s-trans-E diimine system

with a skew aryl group on the 8-imine carbon atom. Other

spectral properties of these diimines were also discussed.

Since the diimines displayed anomalous spectral

properties, further chemical support was sought. It was

thought that a Diels-Alder adduct of one of the diimines

might clarify some of the problems. All attempts to react

a-cyano-4-nitrophenylglyoxylidene-a-(t-butylamine)-B-(2,6-

dimethylaniline) with various dienophiles met with failure.

However, a-cyano-4-nitrophenylglyoxylidene-a-(t-butyhamine)-

>-(2,6-dimethylaniline) did cyclize in base to yield 4-t-

butyl-3-cyano-4,5-dihydro-9-methyl-2-(4-nitrophenyl)-lH-1,4-

benzodiazepine. This compound was transformed further with

sodium hypochlorite to 4-t-butyl-4,5-dihydro-9-methyl-2-

(4-nitrophenyl)-31-1,4-benzodiazepin-3-one. The potential

biological utility of the benzodiazepines made it important

to determine the generality of the base catalyzed cycliza-

tions. For this purpose, a series of unsymmetrically N-sub-

stituted diimines were needed. It was thought that they

could be prepared from a-aminoimidoyl chlorides. A series

of aryl and aliphatic substituted 2-aminoacetamides were

prepared and reacted with thionyl chloride followed by base

to give not the desired imidoyl chloride, but instead-

5-imino-2-oxo-l,2,3-oxathiazolidines in good yield. This

structure was assigned on the basis of analytical, chemical,

and spectral data. Further reactions of the novel ring

system were discussed.













CHAPTER I

Reactions of t-Butyl Isonitrile


Introduction

Compounds of the general structure

for facile molecular reorganization,1-4

Scheme I


X X
'SC=77- Z

//
Y


(1) have the potential

Scheme I.


X
Y'

Y


Recently the iminoaziridines (2 and 3) were prepared by

Quast and Schmitt from the corresponding 2-bromoamidine in

high yield.5 At room temperature they isolated a 50:50

mixture of 2 and 3 and found that 2 started to decompose

at 500C to yield 4 and 5 (half life about 17 hours at 600C)

while 3 on the other hand only decomposes above 120C

into 6 and 7. All attempts to observe the isomerization

(213) either directly or by identification of the isomeric

thermolysis products failed, Scheme II.

Scheme I type isomerizations were observed with imino-

diaziridines. Quast and Schmitt found that when N,N'-di-t-

















I-Bu


Scheme II


t-Bu-C=N-CH3 + t-BuN-C
/ 4 \ 5
t -Bu N CH5


--N N-
CH3 t-Bu t-Bu

2 H 3


t-Bu-C=N-t-Bu
6


+ CH3N=C
7


butyl-N"-methylguanidine was treated with t-butyl hypochlorite
an 83% yield was obtained of a mixture of the isomeric imino-
diaziridines 8a) and (b) in a ratio of 3:2.6 Whereas, 8a and
8b remained unchanged at -200C, at 60-90C either 8a or 8b
led to an equilibrium mixture of the two with less than 2%
thermal decomposition, Scheme IIL This represented the first
Scheme III


II
A
N--N
t-B t-Bu
t-Bu t-Bu


N t-Bu
II

A
N--N
t-Bu CH3








reversible isomerization of a hetero analog of methylene-

cyclopropane. In 1964, Sheehan and Lengyel reported the

thermal decomposition of the spiro-a-lactam (9b).7 This

compound decomposed quantitatively within 10 minutes at

75C to give cyclohexanone and t-butyl isonitrile as major

products, Scheme IV.
Scheme IV


CH2)n

N
I- u


A
-a-


9a n=4
b n 5
c n 7


(CH2)n C=O


Ila n 4
b n=5
C n 7


(CHa2)n 7N-t-Bu

0


/ 10a n= 4
b n=5
c n=7

+ t-BuN=C

5


The results of the thermolyses of 2, 3 and 9 suggested

that heteromethylenecyclopropanes (1) might be generated by

the reverse of this dissociation if suitable acceptors and

conditions were chosen. With this in mind, the isomerization

sequence depicted in Scheme V was attempted under various

conditions.8'9 Although these attempts did not produce

additional examples of the isomerization illustrated in

Scheme V, a number of new and potentially useful reactions








Scheme V


H H
+ N R3
RI-N=C + R2-C=N-R3 R N-3


\'R


+ H
R3-N-C + R2-C=N-RI


H -N-R3


R2


between imines and isonitriles were discovered. It was
found, for example, that benzylidene-N-arylamines reacted
with t-butyl isonitrile to afford a 1:1 adduct (3-t-butyl-
amino-2-phenylindole) and/or a 1:2 adduct [2,3-bis(t-butyl-
amino)azetidine],8'9 Scheme VI. Other systems have formed
Scheme VI


+
+ t-BuN-C-
5


R1
CH-
65
p-NO2C6H4-
C 6H5 -
p-NO2C6H4-
CH3-


+ H,
N-t-Bu
x J\
1 N R


14a
b





5


similar 1:2 adducts with isonitriles. At about the same time,

other workers observed that l,l-ditrifluoromethyl-2,2-dicyano-

ethylene reacts with two equivalents of t-butyl isonitrile

to yield the 1,2-diiminocyclobutane derivative'l and a variety

of aldehydes and ketones react with isonitriles in a ratio

of 1:2 to form 2,3-diiminooxetanes.'1

In spite of these publications,12a coherent picture of

predictive value had not emerged at the inception of this

work. Thus Saegusa et al.13 found that alkyl isonitriles

reacted with two equivalents of benzylidene-N-alkylamines in

the presence of AlCl3, SnC14 or BF3 etherate to produce an

imidazolidine derivative, Scheme VII. However, when cyclo-

hexyl isonitrile was allowed to react with N-arylimine (12a)

Scheme VII

R

+ 1) AIC3 H N
R-N C + C=P =N
H R' 2) H20 R N H R



15
a R=C H R'=CH3

b R=C H R'=C2H5

c R=t-Bu, R'=CH3

in the presence of AC13 they obtained an acyclic product,

N,N'-diphenyl-l-phenyl-2-cyclohexylimino-ethylenediamine (17),

instead of the indole (14a) obtained by Deyrup et al.,8,9

Scheme VIII.







Scheme VIII



Q AICI3
NC + CZN C
16 N12a H
\ H-NH N
H\ C-C
N-0 N

N

H 17


Further work in these laboratories also had revealed the
complexity of isonitrile-imine chemistry. Yun9 reacted
t-butyl isonitrile with p-nitrobenzylidenealkylamines in a
variety of solvents. Instead of the imidazolidine deriva-
tives13 she obtained a,3-diamine-p-nitrocinnamonitriles.9
However, her results varied rather drastically with a change
in solvent. As a result products were obtained for which no
structure had been assigned.
The purpose of this research was to react t-butyl
isonitrile with g-nitrobenzylidenealkyl- and arylamines in
a specific set of reaction conditions in order to obtain
definitive results. The cyclic and acyclic products were
isolated and identified. The interesting chemical aspects
of these products were also surveyed.









Discussion

At the inception of this research no trend could be

discerned among the maze of reactions between t-butyl

isonitrile and imines, except in the case of the work cited

earlier (ref. 8). Some of the reactions were conducted in

carbon tetrachloride in sealed tubes, while others were

conducted in chloroform or methylene chloride, with or without

hydrogen chloride and at or above room temperature. Every

alteration of the reaction conditions produced a different

set of adducts. Even a given set of reaction conditions gave

irreproducible results. Many of the structures could only

be tentatively assigned, if at all. In order to obtain a

coherent set of results of predictive value, a set of reaction

conditions had to be established which would give consistent

results. Initial efforts concentrated on three imines, which

lacked N-aryl electrons available for cyclization (Scheme VI).

Yun had determined that the sealed tube reaction between

p-nitrobenzylidene-t-butylamine (18a) and t-butyl isonitrile

in carbon tetrachloride gave a,3-di-t-butylamino-4-nitrocin-

namonitrile (18a) in a 7% yield.9 Since the yield was not

satisfactory, this system was examined first.

Hydrogen chloride and possibly water were believed

necessary for the reaction between the imine and t-butyl

isonitrile. Thus a preliminary series of reactions was con-

ducted whereby 1.5 mmol of p-nitrobenzylidene-t-butylamine

(18a) were reacted with 4.5 mmol of t-butyl isonitrile in

50 ml of wet solvent"1 which had been saturated with









Table I

Preliminary Reactions


02N




C=N
H t-Bu


Reaction
Letter


+ t-BuN=C-

5


N-EC


bp 760 HCla H20b
mm Hg g/l min%


Solvent


A CHC13

B CCI4

C C6H6

D C 12

E C6H5CH3




F C6H5C1


G 1,3,5-(CH3)3C6H3


,N-t-Bu
H


Results


61 19.45 0.02 No 19a


77 6.76


---- Some 19a


80 16.43 0.02 Some 19a

81 5.11 0.001 No reaction

111 16.61 0.02 Better than
B or C, but
still a low
yield of 19a

132 10.95 0.02 High yield
of 19a

164 11 0.02 Decom-
position


aH. Stephen and T. Stephen, Ed. "Solubilities of Inorganic
and Organic Compounds" Vol. 1, part 2, The Macmillan Company,
New York, New York, 1963, p. 994.
bThe water analysis listed on the labels of the reagents
was considered the minimum precent water contained in
these samples.'1









hydrogen chloride vapor. Each system was refluxed for 24

hours, washed with 10% sodium carbonate, dried, and the

solvent removed by evaporation. The resulting oil was

examined by nmr spectroscopy. Table I lists the details

and results of these reactions.

These results show that the reaction conducted in

chlorobenzene (reaction F) gave the highest estimated yield

of 19a. However one question was still left unanswered:

was water also necessary? Three more preliminary experiments

were conducted in the same way as described for Table I

except that these reactions were conducted in a nitrogen

atmosphere and the moisture content was varied. Table II

lists the variations and results of these experiments as

determined by nmr spectroscopy.

The results indicated that the moisture content of these

reactions was important. Experiment F-l indicated that

Table II

Variations on Experiment F

Experiment Variation Results
No.

F-l The chlorobenzene was dried Very low yield
with anhydrous MgSO4 and of 19a. Almost
saturated with dry vapor, no reaction.

F-2 Used the same conditions as Same result as
described in Table I except experiment F.
that the t-butyl isonitrile
was added in two equal portions
in 12 hour intervals.

F-3 Added 4 ml of conc. hydro- Entirely different
chloric acid,then saturated results.
the solvent with HC1 vapor.








moisture was necessary for the reaction, but experiment F-3

indicated that too much water was also detrimental to the

success of the reaction. The solvent had to be wet, but

not to the point of having droplets of water suspended in

the system.

Similar preliminary reactions were conducted between

t-butyl isonitrile and p-nitrobenzylidene-2,6-dimethylaniline

(18b) and p-nitrobenzylidenemethylamine (18c) in order to find

an appropriate solvent and reaction conditions to optimize

the yields of 19b and 19c respectively. From these results

preparative reactions were conducted in a wet solvent sat-

urated with hydrogen chloride vapor. The major productsis

and their yields are depicted in Scheme IX. A mechanism

Scheme IX



02N


Q N NN-R

C=N + t-BuN--C-
H R 5 N=-C N-t-Bu
18 H
19
a R=t-Bu a R=t-Bu 23%

b R=2,6-(CH3)2C6H3 b R=2,6-(CH3)2C6H3 27%

c R=CH3 c R=CH3 17%



is proposed to account for the major product of these

reactions in Scheme X.








Scheme X


02N


44
C=N + t-BuN=C-
/ \
H R


02N




H++
C=N +
H R"

C=-N-t- Bu


N-R


t-B uN=-C


02N N-R
N-R

N=C N-t-Bu
I -


t-BuNN
v








The nmr spectra of 19 show characteristic similarities.

When the B-nitrogen is bonded to an alkyl group the t-butyl

group bonded to the a-nitrogen appears at 1.206, but at

about 1.376 when the B-nitrogen is attached to an aryl group.

The a-N-H group appears at 1.80-2.006. The B-N-H group,

which appeared as a quartet in the case of 19c, appears

at about 6.006 when R=alkyl and at about 7.006 when R=aryl,

and the p-nitrophenyl group appears as an AB quartet with

JiB=8.5 Hz, 1 1-3 = 2-4 | = 41 Hz,16 and AAB =40.1 Hz.16

The infrared spectra of 19 shows an N-H band at 3.091,

and a nitrile band at 4.60. The mass spectra exhibit

molecular ions consistent with the expected molecular weights.

Compound 19a had been prepared before as an orange solid.9

This modification was also obtained in the present work and

the spectral results were identical to those previously

reported.9 However, a yellow modification was obtained

which had nmr and mass spectra which were identical to the

orange modification. The melting point was considerably

higher and the infrared spectrum was slightly different in

the "finger print" region. Whether the two modifications

were due to two geometrical isomers or to two crystalline

modifications could not be determined unequivocally without

further physical data, i.e. x-ray analysis. It was found,

however, that the modifications were interconvertible simply

by seeding a solution of 19a with a crystal of the desired

modification. The yellow modification was easier to isolate.









The structure of 19a was also established by preparing

it by an alternative route. Kornblum et al. had shown that

dimethylsulfoxide oxidized p-nitrophenacylbromide (21) to

g-nitrophenylglyoxal hydrate (22).'7 It was found that the

crude hydrate (22) would react with t-butylamine under mild

conditions to give an a-mono-imine (23). In order to force

the B-carbonyl to react more stringent conditions were

required. When 23 was reacted with t-butylamine and titanium

(IV) chloride,18 the diimine 24a was obtained.

It has been shown that imines react with hydrogen

cyanide.19 The aldimine, since it is a derivative of an

aldehydic carbonyl, was expected to be more reactive towards

addition reactions than the ketimine. Thus the diimine (24a)

reacted with one equivalent of acetone cyanohydrin to yield

19a in good yield, Scheme XI. Apparently tautomerism of 25

is faster than the reaction with a second equivalent of

acetone cyanohydrin since no diaddition products were observed.

The material was obtained as the yellow modification.

A second product was isolated from the reaction of

p-nitrobenzylidene-t-butylamine. This compound, 20a, was

isolated in a low yield as white needles. This product is

believed to have resulted from air oxidation of the crude

solution of 19a during the purification procedure.20 Its

structure proved elusive because of its anomalous spectra.

These spectral properties will be discussed in Chapter 2.

A third product was isolated in low yield from the same

isonitrile reaction and was identified as an imidazole (21a







Scheme XI


0
I) DMSO OH
SBr2 C
2) H20 I OH
02N 22


02N
S N-t-Bu

H N-t-Bu
24a


(CH3)2S + HBr


I t-BuNH2
S-2 H20

02N

t-BuNH2 / 0

TiCI4 H N-t-Bu
23


SN-t-Bu

H


H
,N-t-Bu


02N









or 22a) from its nmr, ir, and mass spectra. Without further

evidence, it was not possible to distinguish between alterna-

tive structures l-t-butyl-5-cyano-4-(4-nitrophenyl)imidazole

(21a) or l-t-butyl-4-cyano-5-(4-nitrophenyl)imidazole (22a).

Subsequent fortuitous results (to be discussed later) allowed

assignment of structure 21a. The product is believed to

have resulted from the condensation of 19a with a protonated

molecule of t-butyl isonitrile with the subsequent loss of

t-butylamine and a t-butyl group. However, it is also

possible that t-butyl isonitrile which has hydrolyzed to

N-t-butylformamide could also condense with 19a to give 21a

with the loss of water, t-butylamine, and a t-butyl group,

Scheme XII.

The minor products obtained from the reaction of 18a

with t-butyl isonitrile stimulated ideas for further chemical

reactions of 19. An attempt was made to convert 19a to 20a

by oxidizing the former. After several unsatisfactory pro-

cedures were tried, it was found that 19a reacted spontaneously

with sodium hypochlorite (Clorox) at room temperature to yield

20a in good yield. Similarly 19b and 19c reacted with Clorox

to form 20b and 20c respectively in good yields, Scheme XIII.

It seems probable that an intermediate N-C1 derivative under-

goes base induced elimination to 20.21 However, the system

can also be treated as an enamine allowing a different

mechanism to be written22 (Scheme XIV).

It was thought that the diamines 19 might be precursors

to the imidazoles. It has been shown that a convenient







Scheme XII


02N.


H
N-t-Bu
H-CE=N-t-Bu
"N-t-Bu
H


02N H+ t-Bu
N ,NH-t-Bu

NEC N H
t-Bu







02N t-Bu
-/
N N I NH2-t-Bu

NEC "N H
t-Bu


02N H
N-t-Bu
SC=N-t-Bu
NEC /N' lH+
H- t-Bu







o2N H.
S N-t-But-Bu
SC6=N
N-C N H H
t-Bu







02N
\. -H

N N
t-Bu







Scheme XII (continued)


N-t-Bu H

NEC N-t-Bu HN
H t-Bu


N=EC


02N f H
N-t-Bu
H

t-Bu
H


02N t-Bu
I


N N OH2
t-Bu


02N ,,


N--C"N
NE-C N
t-Bu


N=C


.t-Bu








Scheme XIII


H
,N-R


a R=t-Bu
b R=2,6-(CH3)2C H3
c R=CH3


H
N-R


'N-t-Bu


02N"

NoOCI N-R

CH30H N-C C N-t-Bu

20


a R=t-Bu
b R=2,6-(CH3) 2C6H3
c R=CH3


Scheme XIV


--OH
02N H
N-R
HOCI

NEC N-t-Bu
,1-
c02



02N









method for preparing benzimidazoles is realized by reacting

o-phenylenediamine with triethylorthoformate.23 However,

in order for the imidazole ring to become aromatic,either

the R group or the t-butyl group would have to be expelled.

Since an imidazole ring was obtained during the preparation

of 19a it was hoped that the same imidazole could be obtained

from the reaction of 19a with triethylorthoformate. This

reaction did yield an imidazole whose spectral properties and

melting point were identical to the compound obtained earlier.

Since both nitrogen substituents were L-butyl groups, no

unequivocal structure assignment could be made between 21a

and 22a. However a reaction of 19c with triethylortho-

formate would allow a distinction between 21a and 22a. If

the methyl group were displaced during the reaction, the

imidazole 21a would be obtained. It seemed just as likely

that the t-butyl group would be lost and the methylimidazole

(22c) would be obtained. Fortunately both imidazoles were

isolated and 21a was identical to the imidazole obtained

from 19a. The diamine 19b also yielded an imidazole, Scheme

XV. A mechanism to account for these products is suggested

in Scheme XVI.

The structures of 19 were supported by further chemical

evidence. Acetylation of 19a and 19b in refluxing acetic

anhydride in the presence of sodium acetate yielded mono-

acetylated products 26a and 26b respectively, Scheme XVII.

Compound 26b had been prepared and identified earlier.9







Scheme XV


02N H
I NC-t-Bu

NMC N-t-Bu

19a



02N CH

N
CH3
N-C N-t-Bu
I
H
19b


C(OE


02N ,
t)3 N
H
NEC N
t-Bu


21a 39%




02N C

HC(OEt)3 N CH3
C- NH
NEC N

22b 47%


02N CH3

HC(OEt)3 N

N=C N
+ 22c 18%


02N
N
H t
-NC
N 21a
t-Bu


13%







Scheme XVI



02N H02N H
HH
N-R .OEt N-REt
HC-OEt -~- OEt
N -C N-t-Bu OEt N -CC NH
i H "F t-Bu



02N R 02N ] H
(---;, ROEt
-H -- 1 ,H
N-C N NEC NH
t-Bu

02N

H
N N
NEC N
t-Bu

Scheme XVII

02N H O 02N N
N-R (CH320 N-R

NEC N-t-Bu CH3CONa N=C N-t-Bu
H
19H3
26
a R=t-Bu a R=t-Bu 66%


b R=2,6-(CH 3)2 c H


b R=2,6-(CH 3)2 c H 75%









Structure 26b showed a carbonyl absorption in the infrared

spectrum at 5.98u indicative of an amide. In the nmr spectrum

the t-butyl groups had shifted from 1.326 in the starting

material to about 1.676 in 26b due to the electron with-

drawing effect of the acetyl group. The nmr spectrum also

indicated an N-H group at 6.426 which is the B-N-H group in

the starting material and a singlet at 2.376 which was

assigned to the acetyl-methyl group.9

Similarly,26a showed a carbonyl absorption in the

infrared spectrum at 5.98p indicative of an amide. Again the

nmr spectrum showed that a t-butyl group has shifted from

1.206 in the starting material to 1.556 in 26a. The nmr

spectrum also shows a N-H peak at 5.106 which is the 8-N-H

group in the starting material and a peak at 2.206 which was

assigned to the acetyl-methyl group. Neither 26a nor 26b

gave a fragmentation pattern in the mass spectra which

unequivocally determined the position of the acetyl group.

When 19c was refluxed in acetic anhydride with sodium

acetate, 26c was not obtained, but instead an imidazole 27c

was obtained, Scheme XVIII. The produce 27c may have formed

from the initial formation of 26c followed by cyclization.

The product gave a molecular ion m/e 242. The acetate

derivative would have demanded m/e 316. The infrared spectrum

indicated no N-H or carbonyl groups. The nmr spectrum showed

two methyl groups. The one at 2.496 is characteristic of a

methyl group attached to a carbon atom in an aromatic ring.

The other methyl group appeared at 3.606 and is indicative








of a methyl group attached to a nitrogen in an imidazole
ring (see the nmr spectrum data for 22c).
The fact that o-phenylenediamine reacts with carboxylic
acids, acid anhydrides, esters, and amides to form benz-
imidazoles23 makes the formation of 27c somewhat expected.
What is difficult to reationalize is why 26a and 26b did not
cyclize to 27b respectively. Three possible explana-
tions are available: (1) When the group attached to the
s-nitrogen is bulky, for example a t-butyl group or 2,6-di-
methylphenyl group, cyclization cannot take place because
of steric interference. (2) Cyclization of 26a and 26b to
27a and 27b respectively could take place during longer
reaction times or 26c would be isolated in shorter reaction




CH3
N CH3 A
1 -I- No Reaction (I)
NH Xylene
NH2
28


H CH3
^.'CHS3 A N
CH3 X />-CH3 (2)
NH Xylene A N
L 30









times. (3) The last explanation is based on an article by

Roeder and Day.24 They found that 28 would not cyclize to

30 in refluxing anhydrous xylene, but that 29 did cyclize

very efficiently to 30. Obviously, steric problems cannot

explain the difference. They indicated that a hydrogen has

to come from each nitrogen to form the mole of water. More

aptly put, the amide group must be able to enolize. If

this is the case, cyclizations in the case of 26 to 27 may

depend on the ease of the loss of the a-6-butyl group to

form the acetamide moiety to allow enolization. In view of

the cyclizations to imidazoles 21 and 22 it would appear

that 26a would not cyclize to 27a because the a-t-butyl

group is not lost at all, but 26b should cyclize to 27b

because formation of 22b indicates fairly facile loss of

the e-t-butyl group. Similarly 26c would cyclize to 27c

for these reasons. Of the three possible explanations it

is believed that the third explanation may be the best and

could be verified by refluxing both 26a and 26b for longer

reaction times in an appropriate solvent.

Although Raman spectroscopy had confirmed the presence

of the nitrile group in 20, confirmatory conclusive chemical

evidence was desired. Usually nitriles will react in 75%

sulfuric acid to yield acids,25 but 20b completely disinte-

grated to a black tar in sulfuric acid.








Scheme XVIII



02-N H 2N H H
N-CH3 (CH3C)20 N-COH3

N1C N Bu CH3CONa NC N--Bu
I 0 -
19c H / 3 2
02N C-- x2-C


l />CH3
NEC N
270





Other possible reactions were then looked at. Compounds
19, 21, and 22 all showed a nitrile absorption in the infrared
and in each case a cinnamonitrile linkage was present in the
molecule. If by some method the double bond could be returned
to the carbons to give the cinnamonitrile linkage, then the
nitrile band ought to be a strong band in the infrared
spectrum again. A Diels-Alder reaction seemed like a good
candidate to accomplish such a transformation.
Yun had attempted to react 20b with dimethyl acetylene-
dicarboxylate. However, no Diels-Alder adduct formed.9
Tomimatsu26 had shown that di- (-N,N-dimethylaminoanil)-
glyoxal (31) reacted with p-benzoquinone to yield an adduct
32, Scheme XIX. When 20b was reacted with p--benzoquinone
under similar conditions no reaction took place, Scheme XX.








Scheme XIX


N(CH3)2







N(C(CHH))2
0 0

N N H



H N(C[13)2 -

31 N(0H3)2

32

An alternative approach was then turned to which employed

an electron rich dienophile to react with the electron

deficient diazabutadiene.27 Ketene diethylacetal was chosen

for this purpose. Instead of a Diels-Alder adduct, an isomer

of 20b was obtained. This isomer was assigned a 1H-1,4-benzo-

diazepine structure (35) Scheme XX. Subsequent experiments

revealed that potassium-t-butoxide, which was present to

stabilize the ketene diethylacetal, was necessary for cycli-

zation.

Structure 35 was a novel and unexpected product and

its structural assignment presented a few initial problems.

The nmr spectrum indicated a t-butyl group at 1.196, a

methyl group at 2.126, a CH2 group at 4.226, an N-H group

at 5.726, and aromatic protons due to a p-nitrophenyl group

and the three protons on the other ring. The mass spectrum








gave a molecular ion at m/e 362. Three structures would
tentatively fit the data (35, 36, 37).


02N

\ CH3 02N CH3

N H CHSNC N
N NI
t-Bu H NEC I

35 H 37
t-Bu 36


The infrared spectrum showed an N-H bond at 2.94p, a
strong nitrile band at 4.53y, and no C=N band. The lack of
a C=N band in the infrared spectrum rules out both 36 and
37. A mechanism to 35 is proposed in Scheme XXI.
Thus the hypothesis that if 20 could undergo some
reaction that would return the cinnamonitrile linkage to the
molecule, then the nitrile band would reappear in the infrared
spectrum was verified by this conversion. With the Raman
spectra, the fact that 20 results from the oxidation of 19
which has a nitrile group, and this cyclization reaction
which allowed the nitrile band to return in the infrared
spectrum, it is certain that the nitrile group is still
present in 20.







Scheme XX


0
II


II
0


02N
Et0 OEt E
+ II -/-
H H N:


20b


02N.


OEt
OEt
H
H


H
--H
OEt
OEt


\,








Scheme XXI


-Ot-Bu


A reaction was conducted with 35 and Clorox in an attempt

to constrict the seven-membered ring into a dihydroquinoline

structure fused to an aziridine ring (38). Instead a new

compound formed whose nmr spectrum showed a t-butyl group at

1.486, a methyl group at 2.156, an AB quartet for a CH2

group at 4.206, and seven aromatic protons. The infrared

spectrum indicated no NH or nitrile groups, but did indicate

a carbonyl bond at 6.08p. The compound was assigned structure

3 Scheme XXII. Thus the nitrile group had finally dis-

appeared both physically and spectrally.

An explanation is in order for the reason that the CH2

group in 35 is a singlet vs an AB quartet in 39. Inspection

of molecular models indicates that there are two possible













N CH3
Ar

/B
1


Ar
CH3





t- u H


conformations of 35. Either conformation allows both protons
to be in the same environment due to the fast inversion of
nitrogen. This brings about a singlet in the nmr spectrum.

02N 02N

S CH3 CH
N NaOCI 7 NC
N C / NECN-- N /
N/
t-Bu H t-Bu
35

02N CH3



N
N=-u 38C

t-Bu 38







Scheme XXII


02N '/, HO- N


CH3
NN

N
NH 02N
t-Bu H l O
35 K


NoOCI N-

02N N


N CH3
N= C

N
1-EBu


In structure 39, if one assumes that the nitrogen attached
to the t-butyl group has considerable sp2 character, and that
the double bond in the 1-position is in the same plane as the
carbonyl group, but not the benzene ring, there are again two
possible conformers. In either conformation the CH2 group
is held rigid. This allows one proton to be shielded by
the pair of electrons on the nitrogen and the other proton













Ar

Ar CH3CH3
-a t-_



t-Bu a
39


would be in a different environment. The two protons would

solit each other to form a doublet of doublets.
At this point it appeared that a set of reaction con-

ditions had been realized which gave consistent results.

When t-butyl isonitrile was reacted with p-nitrobenzy-

lidenealkyl- or arylamine, a derivative of 19 was obtained
as the major product. This would allow us not to be able
to predict the results of a reaction before it was attempted

in the laboratory. The theory was tested.
Based on our previous evidence, if p-nitrobenzylidene-

benzylamine (18d) was reacted with t-butyl isonitrile the ma-

jor product expected would be 19d. However, when the reaction

02N H


'N-t-Bu
I -
H
19d









was attempted, the nmr spectrum of the crude reaction product

indicated that 19d was present in a rather low yield as com-

pared to previous examples, but there also appeared to be

several other products present. Altogether four products

were isolated, Scheme XXIII. Compound 40 was isolated and

characterized earlier.28

Japp and Davidson29 found that when they reacted benzil

with two equivalents of benzylamine in ether at room tempera-

ture they obtained a gummy substance which they believed to

be the diimine (43). However, upon heating the mixture to

100C they obtained a compound with the empirical formula

C28H22N2. They wrote, this material was "formed according

to the equation,"


C14HI002 + 2 C6H5CH2NH2 --- C28H22N2 + 2 H20 +- H2

Compound C28H22N2 (44a) was identified as the C-l benzyl

derivative of lophine (2,4,5-triphenylimidazole). They

verified the structure by reacting lophine with benzylchloride

to obtain 46. Similarly, ethylamine reacted with benzil to

form similar products, Scheme XXIV.

They also repeated some work by Zincke30 who had reacted

phenanthraquinone with methylamine, but were unable to

identify the product obtained. Japp and Davidson proposed

an imidazole derivative 46 for their product, Scheme XXIV.

Similarly, Hinsberg31 had reacted o-phenylenediamine with

two equivalents of benzaldehyde and instead of the diimine

(47) obtained a benzimidazole derivative 48, Scheme XXIV.







Scheme XXIII


02N


lH N \
t--Bu 40 13%

02N-,'
N

NC N
t-Bu 41 5%

+ t-BuN--C
5


02N


N
HN
I H 42 1%


19d 0.4%








Scheme XXIV


+ 2 RCH2NH2


ref. 21


a R=C6H5

b R=CH3


+ 2 CH3NH2


ref. 21, 22








Scheme XXIV (continued)





NOcH N








S47


-N

CH2





48


Thus the transformations to bring about 40 and 41 via

19d are not without analogy. Unfortunately none of the

references cited offer a proposed mechanism to account for

their products.

In order to propose a mechanism to account for structures

40, 41, and 42 a problem is envisaged. The mechanism must

account for the loss of both hydrogens from the benzyl-CH2

group. This same problem, remember, was circumvented in

references 21-23 by writing loss of hydrogen. The same

solution could be used here; however loss of hydride ion and









a proton, or, assuming that oxygen inserted into a C-H bond,

loss of water would also seem reasonable. It has not been

substantiated, but it is believed that a large portion of

the cyclizations took place on the alumina column. The

basis for this is the estimated yield of 19d in the crude nmr

spectrum was much higher than that actually isolated. Oxida-

tion of 19d to 20d might be a facile process which could be

followed by an equally easy rearrangement to 41 and 42. A

mechanism is proposed to account for the products of the

reaction in Scheme XXV.

The structure of compound 40 was assigned from spectral

evidence.27 The nmr spectrum showed a t-butyl group at 1.486,

a phenyl group, a p-nitrophenyl group, and a single proton

at 7.566. The infrared spectrum showed no N-H, nitrile, or

C=N bands. The mass spectrum indicated a molecular ion at

m/e 321.32

The nmr spectrum of 38 showed a t-butyl group at 1.656,

a phenyl group and a p-nitrophenyl group. The infrared

spectrum showed no N-H or C=N bands, but did show a strong

nitrile band at 4.51. The mass spectrum of 41 showed a

molecular ion at m/e 346. It was therefore the nitrile

derivative of 40.

Compound 19d was identified with little trouble. Its

spectral properties were very similar to 19c.

Compound 42 requires a bit more scrutinizing of the

spectral data. The nmr spectrum indicates a t-butyl group at

1.456, an N-H group at 5.056, a phenyl group, a p-nitrophenyl







Scheme XXV


02N




H CH2

7


Enolization/


02N H H


C
II
N
t-Bu

02N H
N-C
HN- t- Bu
H N-t-Bu

02N i 7



H N-t-Bu
H


t-BuN=-=C-
H+


/ H


+~-tB


H H

N- t-Bu/
N-t-Bu Hydride
SShift
02N H H


H N-t-Bu







2 t-Bu
02N


N _
H



H N
t-Bu


09N







Scheme XXV (continued)


02N H H -H

2 N
H ~-
+ N -t-Bu
t-BuN C -


02N H [ii
HrN4


t-BuN:=-::C N-tV-Bu


02N H- H;
N-C

N=-C N-t-EBu
I 1
19d


02N


02N









group, and a single proton at 8.416. The mass spectrum gives

a molecular ion at m/e 348. The infrared spectrum indicated

an N-H band, but no nitrile band and no C=N band.

Based on the molecular weight of 348, four structures

can be proposed: 20d, 42, 43, and 44. The nmr and ir spectra

rule out 20d, because no benzyl-CH2 group appears in the nmr

spectrum and the infrared spectrum shows no C=N, and nitrile

bands which are demanded for compound 20d. Even if one were

to invoke the spectral anomaly of the other derivatives of

20, i.e. weak nitrile bands in the infrared spectrum, compound

20d lacks an N-H group. For the same reasons 43 can also be

removed as a candidate. Compound 44 comes closer to meeting

the spectral demands for this compound; however 44 also falls

short. Compound 44 demands a nitrile band in the infrared

spectrum which is not present in the spectral data. Also the

imine-proton in 44 would not appear at 8.416, but at 7.00-

8.006. Compound 42 does fit the spectral data. The compound

would be expected to show no nitrile or C=N bands in the

infrared spectrum. Furthermore the proton in the 4- or 6-

position of a 2-phenylpyrimidine derivative should appear

approximately in the vicinity of 8.416. Table III lists a

few pyrimidine derivatives with protons in the 4- or 6-position.

It should be reiterated at this point that the reaction

of p-nitrobenzylidene-benzylamine with t-butyl isonitrile adds

another example to the set of consistent results established

in this research. This reaction helped to establish that 19

is the primary product of the reaction between p-nitrobenzy-








Table III

Chemical Shiftsa of H-4 and H-6


Structure


ClI ; SCH3

N
a


CklN- '\ U


H N
CH3,CN N/


HH


CIr N SCH3


Br H
Ha


6Ha



8.37






8.95





9.03







8.53






8.27


aSadtler Index, Sadler Research Laboratories, 3316 Spring
Garden Street, Philadelphia, Pa. 19104.









lidenealkyl- or arylamine and t-butyl isonitrile. However,

the stability of 19 is also important. In the case of 19a

oxidation to 20a takes place to some extent. However, in

the case of 19d oxidation not only takes place but the system

can cyclize. This is the extra variable which makes pre-

dicting the reaction a little more challenging.


Conclusions with Comments for Further Research

At the conclusion of this research a clear, concise

pattern can be envisaged for the reactions of imines with

t-butyl isonitrile. In the presence of an acid catalyst the

imine is first protonated, providing a driving force for

the attack of the first equivalent of t-butyl isonitrile.

Depending on the group attached to the nitrogen, the system

can either cyclize or can add a second equivalent of t-butyl

isonitrile. This system can then cyclize, or enolize and

lose a t-butyl group. Scheme XXVI and Scheme XXVII summarize

in detail the reactions of imines with t-butyl isonitrile

conducted in this laboratory. Reactions analogous to those

discovered by Killion33 (Scheme XXVI) were reported by

Gambaryan et al.,3 Scheme XXVIII.

This research also demonstrated the usefulness of the

diamines 19 as precursors to imidazoles and other hetero-

cyclic rings which would be difficult to obtain by other

synthetic methods.







Scheme XXVI


(H)R

R R
X


H+
t-BuN=_C
H----- >


(H) H
R R N
\ R'
N' X
t-Bu


S /
H R'

R NX

t-B jN C N -t-Bu





I
I R'
R N\\
x
N--C N-t-Bu
H


(19
H R'


-+ -- Bu





R'
RK
N l


t-Bu N
~ + 'i-Bu



R R'



R N
t-Bu t-Bu


t-Bu




R N


HN
t-Bu







Scheme XXVII


=N
H
12


t-euNEC-

H*


a X=H
b X=NO2
2


SN Bu


t-Bu
H


N
X -

HN
H I 14 a-b
t-su


ref. 8,9


t-BuNC


C~iN-t-6u


R R2
c C6H5 H
d -NO2C6 4 H
e CH3 CH







Scheme XXVII (continued)


+ N
t-BuN-C-








()2N

02NN


H R


a R~t-Bu
b R=2,G-(CH3)2C6H3
c R=CH3
d R=CH2 C 6f




02N

N1 N-R


t-BuN=-C N--t-Bu


RI HN/ a NO2
R2

t-Bu N+
NO .


R N
R2

N N
t-fBu t-Bu
13c-e

t-DuN-C-

H+


T- U


ref. 8,9








I H
--=N +
CH -
-C=N-t-Bu


02Ny H
Hi
N-R


'-'I
SCN-t-Bu
-C t-Bu


Present
work and
N-C N-t-Bu ref. 9
I -
H
19a-d







Scheme XXVII (continued)


X




H -R
51 0
X R
a NO2 C6H5

b H C H5
c H CH3
X H
S H ,-

N` o

t-Bu


C6H5
N
C61H5 /I
53
a R=C 611
b R=CH3




C6H5 r/H

C6H5 N R
IN O0
t-Bu


BF3/CH30H


X

N
SR ref. 33
HN 0
t-Bu 52a-c


t-BuN= C C6H5\ 1/
a =N +
BF3/CH30H CgH5) H
-C-N-1



C6H5 OJ

,N-t-Bu


C6H5

C6H5 N54
Nt 0
t-Bu 540


ref. 33


-b








Scheme XXVIII


F3C

)F3=N
F3C /-R
55 0

a R=C6H5

b R=OC2H5


N C

+S


F3C'


ref. 34


56a-b


Recently Honzl and Krivinka35 have reported novel results

from the reaction of t-butyl isonitrile and hydrogen chloride.

They isolated some cis-a,g-di-t-butylaminosuccinontrile

derivatives which resulted by a pathway similar to that

proposed in this research for imines and t-butyl isonitrile

in the presence of hydrogen chloride.

The reactions of imines with isonitriles produce some

very interesting results. These results have stimulated ideas

for further reactions to be attempted. Scheme XXIX lists

a few proposed reactions along with the expected product or

products based on the results shown in detail in Scheme XXVII.








Scheme XXIX is by no means a complete list of possibil-
ities, but representssome chemistry which still has not
been looked at. Also it is very doubtful that all the
products represented in Scheme XXIX are stable. In fact
many of these reactions may not even go in pathways analogous
to those proposed. Whatever pathway these reactions would
follow, it might lead to a very interesting product which
might serve mankind in some beneficial way. This is the
most anyone could hope for.
Scheme XXIX


R1 \

R2


H R RI N F NR 2 R2,N> NRI
+ 5 --- +
//-\ V--
N N N N
t-Bu t-Bu t-Bu t-Bu


H
+ 5


RI
=C=N
R2 R3


(CH2)n C=N + 5


n=2-6


RI

R2 N

N N
I I
t-Bu t-Bu


(CH2) ,R
N

N N
I I
t-Bu t-Bu


H+







Scheme XXIX (continued)


(C H.-)-
SC=N
RI N \
n= 1-5


R /H
=N-N
H R2





Rh =N--N R2

H R3


R)=N-NR
R2 R4


(CH2)n



N N
t-Bu t-Bu



+ 5 N I O
+ 5 -- 1- : 1 NO-
HN "
I
t- Bu


H+
+ 5






H'
- 5 --


+ 5


RI N-N-R2

N--C N-t-Bu
I -
H


y ,R2
RI N-N

NEC N-t-Bu
I
H


RI RI3
H' R2 NNR4

N N
t-Bu t-Bu







Scheme XXIX (continued)


R RI


/R NN /

t-Bu t-Bu t-Bu
+

RI


Nt -
t-u t-Bu


H+
+ 5


R '
R2 COR3


+ 5


H
R I N-OR2

N-=C N-t-Bu
I -
H


RI
R2 N,-0R


//-Bu -Bu
t-Bu t-Bu


RI H Ri H H H
SRI N-R3
RN/R3R 3 5 H' R2T
/ N +J
N F-N -
t-Bu R3


RI /N H
2=N-N
R/ R3


+ 5


R -

F1 'OR2







Scheme XXIX (continued)


H H
RI R2
R| )=N
H


H
H N-R2

+ R H
+ 5 +
HN N N=C N-t-Bu
t-Bu R2 H


+

H H
FZ 1\ 1 N-R2
H
N=C N-t-Bu
I -
H


H RN\
H R3 RI H R3
R /\ H0R '0 RN
=N 0 + 5 -

R2 N N N
I I I
t-Bu t-Bu t-B



R! RI H













CHAPTER II

Evidence for the Structure and Conformation of
Conjugated Diimines


Introduction

In Chapter I a series of compounds was described which

had been isolated from the oxidation of 19 and which had ab-

normal spectral properties. A similar compound had previously

been obtained by Yun,9 who prepared 20b from the reaction of





02N 02N .
N-R 0 N-R


N=C N-t-Bu NEC N-t-Bu

H 20
19

a R=t-Bu a R=t-Bu

b R=2,6-(CH) 2C6H3 b R=2,6-(CH3)2C6H3

c R=CH3 c R=CH3

19b with m-chloroperbenzoic acid. Although she proposed

structure 20b for the major product, this structure was dif-

ficult to reconcile with its anomalous temperature dependent

nmr spectra, the lack of a distinct nitrile band in its in-

frared spectrum, and the fact that it did not form a Diels-

Alder adduct with dimethyl acetylenedicarboxylate. For this








reason she

compound:


also considered three other structures for this

57, 58, and 59.



CH 0 CH3H
CH3 02N CH3


02N H3 02N CH3


CH3 C[H3
N'C-C N-t-Bu N
/1
20b N 59
t-Bu

The problem was ultimately left unresolved.

It is the purpose of this chapter to explain the anom-

alous nmr spectra for the compounds resulting from the oxida-

tion of 19, and to present further examples of compounds made

by other synthetic routes which show similar nmr spectral

results. The significance of the weak or absent nitrile bands

in the infrared spectra will also be discussed.

Discussion

In Chapter I, it was shown that the oxidation of 19 a-c

with sodium hypochlorite (Clorox) yielded 20 a-c. The fact









that the structures of 19 a-c were firmly established was




N-R NaON-R


N C N-t-Bu CH3H NE-C N-t-Bu

19 H 20
a R=t-Bu a R=t-Bu

b R=2,6-(CH3)2CH3 b R=2,6-(CH3)2C6H3

c R=CH3 c R=CH3

initially the most important piece of evidence for assigning

the structure of 20 a-c as derivatives of a-cyano-4-nitro-

phenylglyoxylidenediamines. Mass spectral evidence indicated

that 20 a-c had molecular weights two units less than their

respective starting materials, 19 a-c. In each case the

infrared spectrum showed a C=N- band and an extremely weak

nitrile band. The weakness of the band allowed the (erro-

neous) conclusion that no nitrile group was present. The

nmr spectra were equally unenlightening.

The nmr spectrum of 20a is shown in the Appendix NMR

No. 2. The two peaks at 1.176 and 1.326 were assigned to the

two t-butyl groups. The two peaks at 1.426 and 1.586 were in-

itially left unassigned. The protons attributable to the g-

nitrophenyl groups also seemed peculiar. A portion of the

aryl hydrogen region seemed to be shielded much more than ex-

pected. The two blips at 7.816 also caused some consternation.

The extra peaks could easily be attributed to impurities. Con-

siderable cut unsuccessful) effort was expended in an attempt









to remove these extra peaks by chromatography or recrystalli-

zation from several different solvents.

The nmr spectrum of 20b posed similar problems. Yun

alluded to this fact earlier.9 The nmr spectrum of 20b is

shown in the Appendix NMR No. 5. The two peaks at 1.296 and

1.506 which were very broad were assigned by integration to

the t-butyl group and the peak at 2.016 to the methyl groups.

The aromatic protons appeared in a region from 6.75-8.326.

Again it is evident that a portion of the aromatic region

attributed to the p-nitrophenyl group appears at a higher

field than usual.

The nmr spectrum of 20c, which is reminiscent of 20a,

is shown in the Appendix NMR No. 8. The t-butyl group

appeared at 1.396 and the methyl group appeared at 3.356.

The peaks at 1.586 and 3.536 were initially left unassigned.

The aromatic region showed the same peculiarities as 20a.

Since infrared spectroscopy is an absorption phenomenon

whereby the resulting vibration causes a change in the dipole

moment of the molecule,36 and the Raman effect is a light

scattering phenomenon whereby the intensity of the Raman shift

depends on the polarizability of the molecule,37 frequencies

permitted in Raman spectroscopy may be forbidden in infrared

spectroscopy and vice versa. With this in mind it was hoped

that if the nitrile group was forbidden by infrared selection

rules, it might be revealed by Raman spectroscopy. Compounds

20a and 20b were submitted to Raman spectroscopy.38 The

presence of the nitrile group was confirmed by this spectral









technique. Thus structures 57, 58, and 59, which were

mentioned in the introduction to this chapter, were unequivo-

cally ruled out.

Compound 20b was found by Yun to give a temperature

dependent nmr spectrum.9 These results were repeated in the

present research and are shown in the Appendix NMR No. 6. At

133.50C the nmr spectrum resolved to a spectrum which indi-

cated a t-butyl group at 1.346, the methyl groups at 2.056, a

3 proton singlet at 6.886 due to the 2,6-dimethylphenyl group,

and a quartet due to a p-nitrophenyl group. In terms of the

expected nmr spectrum of 20b, this spectrum was more appealing.

The question at this point was: does 20a also give a

temperature dependent nmr spectrum? Thus 20a was heated in the

nmr probe and the results are shown in the Appendix NMR No. 3.

The peaks coalesced until at 128C an nmr was obtained which

seemed much more compatible with the nmr spectrum expected for

20a. It showed two peaks at 1.256 and 1.376 to account for

the t-butyl groups and a quartet for the p-nitrophenyl group.

In summary, the evidence presented here: resolution of

the nmr spectra, confirmation of the nitrile group by Raman

spectroscopy, the correct molecular weight, and correct

analysis, plus the chemical evidence presented in Chapter I,

provides ample proof for the strictures assigned to 20.

However, the anomalous temperature dependent nmr spectra still

required explanation in order to secure the structure. For

this reason a series of model compounds were prepared in a

manner similar to that shown in Scheme IX. For convenience

the discussion will be recapitulated here.








Kornblum et al.17 had shown that phenacylbromide and

4'-substituted-phenacylbromides were oxidized by dimethyl-

sulfoxide to the corresponding glyoxal hydrate. Schemes

XI, XXX and XXXI give examples of this reaction.

p-Nitrophenylglyoxal hydrate (22) reacted with one

equivalent of t-butylamine under mild conditions to give

p-nitrophenylmlyoxylidene-a-t-butylamine (23). The use of

titanium (IV) chloride'8 allowed the addition of a second

equivalent of t-butylamine to give the diimine 24a, Scheme

XXX.

The nmr spectrum of 24a is shown in the Appendix NMR No.

10. Note that the nmr spectrum shows four t-butyl groups,

two aldimine C-H groups, and two p-nitrophenyl groups. Each

pair of t-butyl groups was in approximately 45:55 ratio.

Proctor and Rehman39 had shown that phenylglyoxal reacted

with aromatic amines to give derivatives of 23. However, they

also isolated a second compound 60. It was necessary, there-

fore, to demonstrate that this nmr spectrum was not due to a

mixture of 24a and 61. The infrared spectrum confirmed the






R N N R
I I I
060

H H 60

absence of an N-H group and also did not reveal a carbonyl

group. The mass spectrum indicated a molecular ion at m/e

289 which corresponds to 24a and no peak was observed at








Scheme XXX





0 O
II 1) DMSO OH
~) CH2Br ) H20-- -OH
02^^^ NONH
2 21 22

(CH3)2S + HBr


t-BuH2
-2 H20

0)2 I 02N
Nl-t-u t!-BuNH2 <0

H N-t-Bu TiCI4 H N-t-Bu
24a 23



m/e 307 as would be expected for 61. The analysis for 24a
checked for C16H23N302. Therefore, these data coupled with
the fact that similar compounds give a temperature dependent
nmr spectrum, indicate that the nmr spectrum of 24a is a
mixture of isomers.
02N "



t-Bu-N N-t-Bu
HL H 61









The phenyl analogue was also prepared in analogous man-

ner.'4 Phenylglyoxal hydrate 63 was prepared'7 and reacted with

one equivalent of t-butylamine under mild conditions to give

64 which could not be purified further. Using titanium (IV)

chloride'8 a second equivalent of t-butylamine was added to

form 65. Compound 65 was not purified further,"4 Scheme XXI.

The nmr spectrum of 65 is shown in the Appendix NMR No.

11. This nmr spectrum resembles 24a (Appendix NMR No. 10).

Again the nmr spectrum shows four t-butyl groups, two al-

dimine C-H protons and two phenyl groups.

An opportunity was seen to obtain the phenyl deriva-

tives of 19a via the synthetic methods shown in Scheme XI.

Therefore 65 was reacted with one equivalent of acetone

cyanohydrin to give 67. The addition of hydrogen cyanide

probably formed 66 initially followed by enolization before

the addition of a second equivalent of hydrogen cyanide.

Compound 67 was isolated but lost during a second recrys-

tallization. The compound autooxidized to 68.

The nmr spectrum of 68 was no surprise. It was expected

to resemble the nmr spectrum of 20a and this is verified in

the Appendix NMR No. 13. The two peaks at 1.156 and 1.306

were assigned to the two t-butyl groups. The two peaks at

1.406 and 1.566 were temporarily left unassigned, but were

thought to be due to a second isomer of 68. The aromatic

region indicated the phenyl group plus aromatic protons due

to a minor isomer. It should be noted that the nitrile

band in the infrared spectrum for this compound is also

very weak in analogy to 20a.























M"N-t-Bu

N N-t-Bu


Scheme XXXI


I) DMSO
2) H20


t-BuNH2

T0iC[4


0
II |OH
OH

63

(CH3)2S + HBr


H N-t-Bu


LI .N-t-Bu
N -C
/ N-t-BuJ
H
66


N LN-t-Bu

N=C N-t-Bu
I -
/' H


'i /f


N-C N-t-Bu


/10]


0
II
0^ CH2Br


t-BuNH12
-2 H20









One trend that was definitely revealed by the nmr spectra

was that, as the group on the a-carbon increased from hydrogen

to cyanide, the minor isomer decreased in concentration. It

was thought that if the group at this position could be

steadily increased the effect would be to completely eliminate

the second isomer in the nmr spectra. For this reason

n-nitrophenyl-l,2-propanedione41 (73) was prepared from

p-nitro-a-acetamide-B-hydroxypropiophenone 2 (72), Scheme

XXXII. Unfortunately p-nitrophenyl-1,2-propanedione (73)

failed to yield the diimine (74) either in mild reaction

conditions or with titanium (IV) chloride.18 All that was

obtained was tar.

Once the structures of compounds 20 a-c, 24a, 65, and

68 were established as diimines, an explanation could be

proposed for their anomalous nmr spectra. This explanation

suggests that two conformations are populated at ambient

temperatures and that at this temperature a barrier exists

to their interconversion. Assignment of detailed structures

to these conformations will be made on the basis of (1) the

response of the relative proportions of the two conformations

to changes in steric size of the various substituents and (2)

an analysis of chemical shifts caused by anisotropic groups

in these molecules in comparison to suitable model compounds.

Close inspection of the aromatic region in the nmr

spectra of compounds 20 a-c, 24a, 65, and 68 (Appendix NMR

No. 2, 5, 8, 10 and 11) reveals that each spectrum has two

groups of peaks in the aromatic proton region. This is







Scheme XXXII'4 42



N.N
:H2Br + rN
N, ,N


02N


Ac20


H
>=0
H


CH3


0
CH20H

02N 7HN 0
72 i
CH3


02N Y


02N


HCOOH


CH-


73

t-BuNH2


'N-t-Bu








particularly noticeable in the p-nitrophenyl compounds, e.g.

20 a-c, and 24a. One group of protons ("normal") occurs at

7.836 and 8.226. The other group ("abnormal") appears at

7.256 and 8.226. The peaks at 7.836 and 7.256 correspond to

the protons ortho to the imine group.

Two model compounds, p-nitrobenzylidene-t-butylamine

(18a) and benzylidene-t-butylamine (75), are submitted in

the Appendix NMR No. 14 and 16 respectively as evidence for

a "normal" aromatic ring attached to an imine bond bearing


02N




NN
H -Bu H t-Bu

13a 75



an N-t-butyl substituent. Note that in the nmr spectrum of

18a the protons ortho to the nitro group appear as a doublet

at 8.206 and the protons ortho to the aldimine group appear

as a doublet at 7.896. Similarly, the nmr spectrum of 75

shows the protons in the 3,4 and 5-positions of the pehnyl

ring as a multiple at 7.27-7.506 and the protons ortho

to the aldimine group appear as a multiple at 7.67-7.886.

These aromatic rings are expected to be in the same plane"

as the imine double bond in order to achieve maximum i

overlap. The "normal" ortho protons thus lie in the deshield-

ing area of the imine group.








A model compound for an "abnormal" phenyl group is 2-

methyl-2-phenylpropiophenone oxime, (76).45 In the nmr spec-

trum the protons in the 3,4 and 5-positions of the phenyl

group attached to the oxime bond appear as an upfield multi-

plet at 7.10-7.556 and the protons ortho to the oxime bond

appear as a multiple at 6.53-6.826. In this case the protons

ortho to the oxime bond are shielded by approximately 0.70-

1.006. It is proposed that the aromatic ring is twisted out




OH


CH3 'CH




0 76


of plane due to non-bonded interactions and the ortho protons

thus lie in the shielding cone of the C-N double bond.

From this evidence the orientation of the aryl group in

both conformers of 20 a-c, 24a, 65, and 68 can now be proposed.

In the cases where the aromatic ring appears "normal" in the

nmr spectrum, the aromatic ring is coplanar with the attached

imine group (partial structures 77). In the cases where the

aromatic ring appears as "abnormal," the aromatic ring is

skew to the plane of the imine groups (partial structure 78).

Furthermore, in the case where the aromatic ring is coplanar

with imine bond (partial structure 77), it may be assumed for

steric reasons that the group attached to the imine nitrogen








is E with respect to the aromatic ring," c.f. 18d and 75.






AV /V
77 78

X=H R=t-Bu
X=NO2, R=t-Bu, 2,6-(CH3)2C6H3, CH3

The stereochemical nomenclature used in the rest of

this chapter requires definition. The terms "s-cis" and
"s-trans" have been proposed for the arrangement of groups
around a single bond.4" The two conformations of butadiene

serve as examples of this terminology. The E-Z system is


H
H H

H / H
H

s-trans


H H

H / H
H H


s-cis


used to define the configuration about the C-N double bond.4

The two substituents attached to the carbon linked by a


U Y
-=N


S=N
X Y


Sequence U>X








double bond nitrogen are arranged in the appropriate Cahn-

Ingold-Prelog sequence.50 Then, if the groups of higher

sequence (U and Y above) are on the same side, the configur-

ation is Z (from the German zusammen), if they are on opposite

sides, E (from the German entgegen).

Returning now to the nmr spectra of 20 a-c and 68 the

minor conformer has the planar moiety 77 and the major

conformer has non-planar moiety 78. However, in 24a and 65

this is reversed, i.e. the major conformer has the planar

moiety 77 and the minor conformer has the non-planar moiety

78. With this information a relationship can be invoked.

The more deshielded alkyl groups are associated with the

planar moiety 77 and vice versa the more shielded alkyl

groups are associated with the non-planar moiety 78.

Three possible conformations (79c, 79t, and 79s) can be

suggested for the conformer which contains the moiety 77.

The conformation of the a-imine was suggested to be E in

order to avoid steric interactions.




x R
/ R / R /'R

Y N N Y 'Y
t-Bu t-Bu t-Bu

Z-s-cis-E Z-s-trans-E Z-skew-E
79c 79t 79s

X=H, R=t-Bu

X=NO2, R=t-Bu, 2,6-(CH3)2C6H3, CH3








Overlap between adjacent p-orbitals allows r bonding

between the central carbon atoms (80). In such cases, the

energy is lowest in the planar conformations s-cis (cisoid)

and s-trans (transoid). However, the activation energy

required for rotation about the central bond is generally not

very high.s5 Steric factors and other electronic factors52





QQN




80

could swing the balance away from a planar minimum towards

a variety of skew conformations.

Careful considerations of the nmr spectral data indicate

that the diimine system does favor the planar conformation.

This argument is supported by the observation that as Y in-

creases in size from H to CHN the concentration of the con-

former 79 decreases. If the a-imine group of this conformer

(79s) were skew, the size of Y would be expected to have

little effect on the relative concentration of 79. The

Z-s-trans-E (79t) would be most responsive to the size of Y

and also would accommodate bulky R groups most easily.

Therefore the Z-s-trans-E (79t) conformer is proposed to

be the most favored conformer of 79.

Further evidence which is consistent with a planar

diimine configuration for 79c or 79t is seen in the resonance









line for the aldimine proton in the case of 24a and 65.

Comparison of the nmr resonance line of the aldimine proton

in 24a and 65 with 18a and 75 respectively, reveals that the

former pair is deshielded by 0.106, Schime XXXIII. Similarly

the t-butyl group attached to the --imine nitrogen in 24a and

65 is also shielded by 0.106 as compared to the t-butyl group

in 18a and 75, respectively. Compounds 18a and 75 contain

the planar moiety 77. Therefore the second imine group in



CXR


N 77

24a and 65 must cause the extra deshielding in the system.

Three more models, 81a,53 81b,5s and 82,55'56 are pre-

sented in Scheme XXXIII which support the proposed planarity.

The aldimine proton of an aliphatic t-butyl imine of known

conformation, 81, has a resonance line in the nmr spectra at

7.41-7.466. The conformation of 82 has recently been pro-

posed to be E-s-trans-E with some E-s-cis-E55'56 although

a non-planar species could explain their data.52 The aldimine

proton of 82 has its resonance line in the nmr spectrum at

7.886. These models establish that if the imine group in 79

were skew to the planar moiety 77 the aldimine proton would

be expected to appear in the vicinity of 7.40-7.906. The

fact that the aldimine proton in 79 appears at 8.32-8.396,

gives support that the system is completely conjugated and

therefore planar. Thus it is proposed that the deshielding







Scheme XXXIII


02N



1.306
8.296 H t-BU
18a



02N
.N 1.406
.-Bu

1.30 tB
1.305 t-Bu


i-Pr
N
= \ 1.156
7.465 H t-Bu

81a53


)=N 1.286
8.256 H t-Bu
75





N 1.376
H t- Bu

N 'H
1.326 t-Bu
65


t-Bu

\ 1.126
7.416 H t-Bu

81b"


t-Bu 1.226
7.886 H N


N H 7.886
1.226 t-Bu








anisotropic effects caused by the completely planar conforma-

tion of 79 causes the deshielding of the aldimine proton.

In summary the favored conformation of 79 is completely

planar because of (1) resonance arguments which invoke

some double bond character to the central bond of a diimine

system, (2) steric arguments which show a decrease in 79

with increase in the size of group Y, and (3) deshielding of

the aldimine protons due to anisotropic effects of a com-

pletely planar system. Furthermore, based on non-bonded

interactions, the most favored planar conformation of 79

is Z-s-trans-E (79t).

The discussion is now turned to the second conformer in

the nmr spectra of 20 a-c, 24a, 65 and 68 which has the

non-planar moiety 78. Comparison of the nmr spectrum of

x




N
/V
78

20c with 20a discloses that the t-butyl group attached to


02N 1.196 02N 3.35O
S t-Bu CH3
i.N IN


N C-N N CEN
1.336 t-BU 1.396 t-Bu


20a


20c








the B-imine nitrogen is the most shielded t-butyl group in

the nmr spectrum of 20a (Appendix NMR No. 2). This would

indicate that the t-butyl group attached to the B-imine

nitrogen is in the shielding cone of the aryl group. There-

fore the conformation of the 8-imine is Z with respect to

the aryl group, (83). This would also explain why the aryl

group in the non-planar moiety 78 or 83 is skew. It is


R
N


A/
83

physically impossible for the aryl group to remain in the

same plane as the imine double bond when the N-substituent

is Z with respect to the aryl group because of non-bonded

interactions.

A model compound, the t-butyl imine of benzophenone

(84),18 whose nmr spectrum is shown in the Appendix NMR No.

17, is presented for the chemical shift of a t-butyl imine

group interacting with the shielding cone of a benzene ring.

The chemical shift for the t-butyl group is 1.155 in 84 as

compared to the chemical shift of 1.196, 1.106, 1.106, and

1.166 for similar t-butyl groups in 20a, 24a, 65, and 68,

respectively.













GN /t-Bu
NX
II




84

It has been shown that in benzophenone each phenyl

group is twisted from coplanarity by 410.44 Therefore the

t-butyl group would have to interact with the shielding

cone of one of the benzene rings.

Similarly the methyl imine derivative of benzophenone

(85)18 should serve as a model for the chemical shift in the

nmr spectrum for a methyl imine interacting with the shielding

cone of a benzene ring. The chemical shift of the methyl

group in 85 was found to be 3.136 in carbon tetrachloride.

The corresponding methyl group in 20c appears at 3.356 in

deuterochloroform. The difference could possibly be due to

solvent effects.57-59

OCH3
N




85


As in conformer 79, the 8-imine of the conformer

containing the non-planar moiety 33 is suggested to have the








E conformation in order to avoid steric interactions of the

t-butyl groups with the lone pair of electrons on the 8-imine

nitrogen or the I cloud of the aryl group. Thus three con-

formations (86c, 86t, and 86s) can be proposed for the con-

former containing the non-planar moiety 83.


x x _x

N N N


Y N N Y N Y
t-Bu t-Bu t-

E-s-cis-E E-s-trans-E E-skew-E
86c 86t 86s


Of the three conformers of 86 the E-skew-E (86s) seems

least likely due to lack of stabilization due to resonance.

The E-s -is-E conformer (86s) also seems unfavorable due to

the severe electronic repulsions caused by the lone pair

of electrons on each imine nitrogen. The E-s-trans-E

conformer (86t) seems to be favored because it minimizes non-

bonded interactions and is stabilized due to the planar con-

figuration of the diimine system.

The aldimine proton in this conformer is 24a and 65

should show the nmr spectrum resonance line consistent with

the resonance line of the alkimine proton in 82. As was men-

tioned earlier the conformation of this compound is proposed

to be E-s-trans-E.55'56 The aldimine proton in this conforma-

tion in 24a gives an nmr resonance line at 7.936 and in 65 a







resonance line at 7.976 which is in good correlation with
the model. This also gives evidence that the aldimine proton
is s-trans to the aryl group because if it were s-cis the


02N


t-Bu
H N



t-tBu


24a


t-Bu

65


aldimine proton would be much closer to the shielding cone
of the aryl group and would therefore be expected to be more
shielded than the aldimine proton in 82.
Further predictions for this system can be made and
compared with observed data. If the t-butyl group in the
planar diimine 82 is used as a standard, one would expect
that the t-butyl group attached to the B-imine nitrogen in
conformer 86 to be shielded by no more than 0.15660 due to


02N



q-N
0NN 1.306
8.296 H t-B1

18a


/ \ 1.156
^ t-Bu


84


N N\ 1.286
8.256 H t-Bu

75


interaction with the shielding cone of the aryl group.








Inspection of the nmr spectra of 20a, 24a, 65, and 68

(Appendix NMR No. 2, 10, 11, and 13) confirms this result.

The shielding cone of the aryl group would be expected

to shield the t-butyl group attached to the a-imine nitrogen

when the diimine system is in the s-trans configuration.





/ I



? Y

I:- 3u
86t


However, this shielding would be expected to be weakened

because the t-butyl group is much further away from the aryl

groups and also because the t-butyl group is close to the

periphery of the shielding cone. Inspection of the nmr

spectra of 24a and 65 reveals that this prediction is also

correct. The t-butyl group on the a-imine nitrogen appears

at 1.156 and 1.136 in 24a and 65 respectively. Thus, compared

to 82 the t-butyl group is shielded by less than 0.106.

In order to discuss the t-butyl group attached to the

a-imine nitrogen in 20a and 20c another model is needed.

Compound 87 should serve as this model. In this model in the

3-position the t-butyl group on the imine nitrogen has a

chemical shift in the nmr spectrum similar to that found in

82. However in the 2-position the imine is conjugated with










02N 1.196 1.236 02N 3.356
t-Bu t- -u CH3

1\4 7.706 H N N


N C-N N C--N N CN

1.336 t-BU 1.426 t-BU 1.396 t-BU

20a 87 20c


a nitrile group. Due to resonance and inductive effects this

nitrile group deshieldsthe t-butyl group by about 0.206.

The t-butyl group attached to the a-imine nitrogen in

20a and 20c would be expected to appear around 1.426 if the

aryl group were not present in the molecule. However the

t-butyl group is interacting with the shielding cone of the

aryl group. The aryl group shields this t-butyl group by

about 0.106 or less, cf. 24a and 65. Therefore one would

expect this t-butyl group in 20a and 20c to appear in the

range 1.32-1.426. Inspection of the nmr spectra of 20a and

20c reveals that the predictions are in good agreement with

the results, i.e. the t-butyl group appears at 1.336 and 1.396

in 20a and 20c respectively.

Another trend which can be observed in the nmr spectra

of 20 a-c is that as the substituent on the 3-imine nitrogen

is varied in size from methyl to t-butyl to 2,6-dimethylphenyl

the concentration of 86t decreases while 79t increases. It

is proposed that as the substituent on the B-imine increases

in size the r cloud on the aryl group interacts with this









substituent to a greater and greater extent. When this

interaction becomes too great isc nerization of the 6-imine

nitrogen is favored to form conformer 79t in order to relieve

this non-bonded interaction.

In summary the conformation of 86 is proposed to be

E-s-trans-E with the aryl group skew to the plane of the

diimine system because (1) the protons ortho to the diimine

system in 86 are shielded because of their interaction with

the shielding cone of the C-N double bond, (2) based on

resonance argument the planar diimine system is of lower

energy and therefore more stable, and (3) it eliminates non-

bonded interaction more so than the s-cis conformation.

Furthermore the conformation of the B-imine nitrogen is E in

order to explain the forcing of the aryl groups out of plane

and thus this twisting limits non-bonded interactions.

The overall equilibrium which is observed in the nmr

spectra of 20 a-c, 24a, 65, and 68 is shown in Scheme XXXIV.

The diimine system remains planar and the a-imine keeps an E

conformation. However the B-imine nitrogen isomerizes from

Z to E and with this isomerization forces the aryl group out

of plane. When R becomes large the non-bonded interactions

of R with the i cloud of the skew aryl group become too great,

forcing the equilibrium back to 79t. When R is small the

equilibrium favors 86t. However when Y is small 79t is

favored but when Y is large 86t is favored.

Recently Kliegman and Barnes55'56'6'6'2 have reported

on the nmr and conformational studies of the diimines (88)








Scheme XXXIV


X -X


X R N

N Y N Y
t-8u t-8u
Z-s-trans-E E-s-trans-E
79t 86t

X=NO2, Y=C-N, R=t-Bu, 2,6-(CH3)2C6H3, CH3

X=H, Y=CN, R=t-Bu

X=NO2, Y=H, R=t-Bu

X=H, Y=H, R=t-Bu
of glyoxal. They "established" that the most stable confor-

mation of conjugated 1,2-diimines of glyoxal was E-s-trans-E

(88t), with a small amount of the E-s-cis-E conformer (88c).

This was accomplished by analysis of their nmr spectra and

by titration with 0.1N HC104 in acetic acid.



H N H N


N H- H 'N
R R
88t 88c




Their data do not "prove" that the most stable con-

formation of conjugated 1,2 diimines is E-s-trans-E. The








nmr spectral data argument for an E-s-trans-E conformation

was based on comparison with aliphatic imines with presumably

E conformations. Their nmr data can be said to be consistent

with but not proof for an E-E conformation for the diimines.

The conformation about the central C-C bond (s-trans, s-cis,

or skew) cannot be determined from these data. All the

chemical evidence established was that they could trap the

E-s-cis-E conformer (88c) irrespective of its stability in

solution.

Sheppard et al.63 reported that diiminosuccinonitrile

(89), on the basis of the proton nmr and dipole moment, was

primarily transoid in structure. The major conformer was

either 89a or 89b and the minor conformer was 89c.


H


OR H,- C
N CN)N C N N CEN
H H
E-s-trans-E Z-s-trans-Z E-s-trans-Z
89a 89b 89c

A dipole moment study was attempted on the conjugated

1,2-diimines of glyoxal.52 In general, the measurements were

not very precise because of association in solution, thus

making extrapolation to zero concentration difficult. Their

results could be interpreted in terms of a mixture of 88t

and 88c or as a non-planar conformer 88s. However, on the

basis of the results on 1,2-diketones they preferred the












N( 0=90-1400


R-N "- N-R

88s"2


latter 88s. However, is this consistent with the results

of 1,2-diketones?

It has been demonstrated that the effective (or average)

conformations of benzil (90, R=C6 s), furil (90, R=C4H30),

and biacetyl (90, R=CI3) in non-polar solvents are one in

which the ketonic groups, with their appropriate bonds, are

non-planar (as in 90) with azimuthal angles XO ca. 970, 118.50,

and 1600 respectively.64'65 The conformation of furfur-

aldehyde was found to be s-trans (91). The skew structure












benzil R=C6H5 X=97
X










furil R=CIH30 X=118.50
biacetyl R=CH3 X=1600

for the 1,2-diketones 90 was suggested to he caused by

non-bonded interactions between the R group and the carbonyl

oxygen. However the trend is evident. As R in 90 becomes








smaller the 1,2-diketone tends towards the s-trans conforma-

tion. Further extrapolation from this evidence, including

the fact that the most stable conformation of 91 is s-trans,

would suggest that glyoxal (92) ought to have an s-trans con-

formation,not the skew structure proposed by Kliegman and

H -O


O H
92
Exner.52 Therefore one would expect that the most stable

conformation of the conjugated 1,2-diimines of glyoxal to be

planar based on the resonance arguments (80) and the'evidence

presented above. Furthermore the dipole moment measurements

should be interpreted in terms of a mixture of 88c and 88t

instead of 88s.

In the present work two more diimines, the di-t-butyl-

imine derivative of benzil 93 and 4,4'-dinitrobenzil 94 were

prepared. The nmr spectra of 93 and 94 are shown in the

Appendix NMR Nos.18 and 19 respectively.

02N

N-t-Bu N-t-Bu
1.226 1.266

N-t-Bu N-t-Bu

02N
9366 9466

Perusal of the nmr spectrum of 93 and 94 indicates that

in each case only one t-butyl group and one aromatic multi-

plet is observed. Note that in 94 the E-nitrophenyl group is









exactly the same as that shown for p-nitrobenzylidene-t-butyl-

amine (18a) (Appendix NMR No. 14). In fact the nmr spectra

of 18a and 94 are identical if the aldimine proton is removed

from that of 18a. The same statement can be made for 93

and 75.

From the nmr spectra it is obvious that the aromatic

rings are in the same plane as the imine group to which it

is attached. Inspection of molecular models indicatesthat if

both imines are in an s-trans configuration, it is impossible

for both aryl groups to remain coplanar with the diimine

system. Similarly if both imines are in the s-cis configur-

ation, both aryl groups again cannot be coplanar with the

diimine system.

The explanation is very simple. It has been shown that

"the stable configuration of benzil in non-polar solvents is

one in which the ketonic groups, with their appropriate bonds,

are effectively situated in, or make rotational oscillations

of low amplitude about, two planes which are roughly mutually

perpendicular.""6'65 The same effect explains the nmr spectra

for the benzilylidenedi-t-butylamines 93 and 94, Scheme XXXV.

In other words, when Y is very large 79t is destabilized due

to non-bonded interactions. Furthermore a twofold loss of

overlap between the aryl and imine groups is not compensated

for by the overlap of the planar diimine system in 86t.

The discussion thus far has only indicated diimines in

a s-trans configuration or in a skew configuration. It was

interesting to determine if an s-cis diimine could be made.









For this purpose the di-t-butylimine derivative of phenan-

thenequinone (95) seemed like a good possibility. The di-

imine would be held by the rigidity of the system in a s-cis

configuration. Actually it really was expected that this

system couldn't be synthesized because of the severe steric

interactions.

If compound 95 could be prepared it seemed likely that

the system would exist in the Z-s-cis-E conformation. In-

spection of molecular models would verify this. The Z-s-cis-Z

conformer (95a) is physically impossible and the E-s-cis-E

conformer (95c) which according to Kliegman and Bar-

ness5'56'61'62 is the more stable conformation of some

diimines, would also seem to suffer because of steric inter-


i .B Bt-Bu



-Bu-Bu -Bu
t-Bu




Z-Z Z-E E-E

95a 95b 95c


actions of the t-butyl groups with the aromatic rings. Thus,

the Z-s-cis-E topomer67 (95b) seems to be most favored.

Phenanthrenequinone was reacted with two equivalents of

t-butylamine in the presence of titanium (IV) chloride.18

The nmr spectrum (Appendix NMR No. 20) showed two t-butyl

groups of equal intensity at 1.226 and 1.506.68 This result








Scheme XXXV

Observed Conformation


93 X=H
94 X=NO2
X=97'


Conformations Not Observed


N -
tB t-Bu



t-Bu
-79

79t


x t-Bu






t-Bu


86t


X=H

X=NO2









thus verifies that the Z-s-cis-E conformation (95b) is the

most favored in solution.

This system appears to have an interesting property.

Since the imines are held s-cis and the t-butyl groups are

held in the same plane topomerization becomes very difficult.

In order for the imine nitrogen in the E conformation to

invert the imine nitrogen in the Z conformation would also

have to invert in a synchronous fashion producing a "wind-

shield wiper effect." Another possibility would be that the

imine nitrogen in the E conformation would have to wait for

the imine nitrogen in the Z conformation to invert to the E

conformation and then rapidly, by nmr time scale, invert to

the Z conformation.

E-Z isomerization of N-alkyl or N-aryl imines usually

takes place rapidly in solution, but some imines have been

found to crystallize in one conformation.69 However, oximes

(97, Y=OH), oxime ethers (97, Y=OR), hydrazones, (97, Y=NR ),

azines (97, Y=N=CR ), and N-haloimines (97, Y=F or Cl) have

in some cases been found to be very resistant to isomerization

in a variety of conditions."9 Compound 95 may very well be

unique, in that the N-alkylimines in solution do not invert

because of the rigidity of the molecule and non-bonded inter-

actions which exist in the system.


N N ) -N
Y .
97


Y=OH, OR, NR2, N=CR2, F, and Cl








One other explanation for the abnormal nmr spectra in

20 a-c, 24a, 65 and 68 should be mentioned. It was thought

that these diimines might be undergoing a thermally allowed

conrotatory electrocyclic reaction," to a A3-1,2-diazetine

(98), Scheme XXXVI. The driving force for this cyclization

would be the formation of a 6r electron aromatic system.

Effenberger and Maier71 supposedly prepared the

Scheme XXXVI


x x
X X.-R X.

NAA

'-y' yNO N-..
N Y Y N Y t-Bu
t-Bu t-Bu

86t 86c 98


A3-1,2-diazetine system but only reported that "they did it."

No evidence was reported to allow the reader a chance to

evaluate the data himself. They did not appear to consider

the thermally allowed conrotatory electrocyclic opening of

this ring to a diimine system. Thus, this reference71 is

open to question.

About this time Beak and Miesel72 examined the photol-

ysis of 2,3-dihydropyrazine (99) systems. Based on previous

work73 they expected a photochemically allowed disrotatory

electrocyclic reaction would take place to yield a bicyclo-

[2.2.0] system (100). However, they obtained instead









imidazole derivatives (102), Scheme XXXVII. This evidence

seems to indicate that structures like 98 or 100 are dif-

Scheme XXXVII





R N R


y 99 100


RN R HN R N H


R N N R R N

101 H H CH2 102 CH3


ficult to obtain.

It seems very improbable for several reasons that 98

would replace 79t in the nmr spectra of 20 a-c, 24a, 65, and

68. The reasons are: (1) As Y is increased in size in 98

there is no explanation why 86t would then be favored since

steric interactions in 98 would also be minimal. (2) In 20c

where the concentration of 86t decreases and the supposed 98

increases the nitrile band in the solution infrared spectrum

should show a strong nitrile band due to the cinnamonitrile

linkage in 98 as was established by 19b, 22b, and 35. (It has

been established that 20b shows a very weak nitrile bond.)

(3) The nmr spectrum of 98 where Y=H would not be expected
















CH3


20b


t-Bu 35

to appear at 8.32-8.936 based on the model compounds 103
and 10473f unless there is a sizeable ring current.




SO _OR^R H
-/H OR


H -NN -H NN H-- N
6.73-6.786 R 6.40-6.506 R 6.56-6.706 R

103 104
Therefore it seems very unlikely that a A3-1,2-diazetine (98)
is being observed in the nmr spectrum of 20 a-c, 24a, 65
and 68 instead of 79t.
The mechanism by which the E-Z isomerization in imine nit-

rogens takes place in an inversion mechanism.51 The N-Y bond of
105 swings in the bond plane of the imine system from the Z
into the identical E position ("in plane" isomerization, c).








The bond angle of (C-N-Y) increases to 1800 in the transition

state. The C=N is, to a first approximation, unaffected.51


X X X.X XX
II II -I-- I

Y
105


XIX



C
It has been shown that there is a similarity of the

effect of the substituent Y on the E-Z isomerization in imines

(105) and on the inversion at tricoordinated nitrogen (e.g.

in aziridines).51 The isomerization rate increases very

rapidly as the substituent Y is varied in the order:

ROR2N carbon also increase the inversion rate in the following order:

quinone ring
thio
The fast inversion rate at nitrogen also explains why

carbodiimides (106) do not form stable isomers. Inversion at

the nitrog.-n is rapid by nmr time scale even at -1000C.1


R ,/R
N=CR N
R J




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