NJ»-
the c3351

It

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AI-”
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me 7

ABSTRACT

STEREOCHEMICAL STUDIES OF NITROSAMINES, OXIMES
AND N-SUBSTITUTED HYDRAZONES BY NUCLEAR
MAGNETIC RESONANCE SPECTROSCOPY

by Robert Arthur Taller

Nuclear magnetic resonance Spectroscopy was used to study
the configurations and conformations of N-nitrosamines, oximes,
N-methylhydrazones, N,N—dimethylhydrazones, and phenylhydra-
zones.

It was observed that whereas ormethyl, ormethylene, and
B—methyl protons of the nitrosamines resonate at higher mag-
netic fields when gi§_than when trans to the nitroso oxygen,
aamethine protons resonate at lower fields. This difference
is attributed to the greater stability of I, whereby the
methine proton eclipses the nitrogen-nitrogen bond. The nature

of the association between benzene and nitrosamine was deduced
6.
N/ N/0

b?
‘ H H R H
N A
/ _‘ ' N \ N
R + “‘-CH3 Rk/+\R2 R‘ ”’j/+\R
CH3

/0

I II III

 

 

A .. fi Fa
. i. ‘ i
L.» #t w;

my“ WW .7“ .w. «~«~ .‘AA “1L
5 L; .t R v. ML b.
D +t 8 WI
a L.» e 1
flu a la "V e 1.... S
.\a S .hu .1 .n a 5
.NJ .6 L» t st FL «G

 

 

and sol.

.

'h
‘tey
‘

 

Robert Arthur Taller

by observing the proton resonance shifts of groups R; and R2
as a function of benzene concentration. These studies showed
that the benzene molecule interacts with the partially posi-
tive nitrogen atom in a way that places the ring closer to
the trans than to the gig protons (II). Changes in the chemi—
cal shifts of the trans isomers are consistent with the
assumption that the minimum energy conformations are those in
which the nitrogen-nitrogen bond is eclipsed with a substituent
on the tetrahedral carbon (III).

The spin-Spin coupling interactions between H; and Ha

of aldoximes (IV) were studied as functions of temperature

 

and solvent. The data were interpreted in terms of rotamers
N///OH
Ha J
R
IV V VI

where a single bond eclipses the carbon-nitrogen double bond
(IV and V). In all cases IV is stabler than V. The effect
of benzene on the chemical shifts was interpreted in terms of
VI, whereby the benzene molecule interacts with the sp2
hybridized carbon of the oxime and is situated §p£i_to the
hydroxyl group.

The stable conformations about the nitrogen-nitrogen

single bond of aldehyde and ketone N—methylhydrazones was found

 

 

"V‘
(12....

.
"“flv‘
‘

nAVM-

Robert Arthur Taller

/®’CH3 3 X“
‘N

VII VIII IX

to be VII. That of aldehyde N N—dimethylhydrazones was the
analogous conformation VIII. As a result of nonbonded inter-
actions ketone N,N-dimethylhydrazones assume conformation IX.
The effect of solvent on the chemical shifts of phenyl-
hydrazones led to the conclusion that extensive self-associ-
ation and hydrogen bonding between phenylhydrazone and solvent
exists. Plausible structures of these hydrogen—bonded com-

plexes are suggested.

STEREOCHEMICAL STUDIES OF NITROSAMINES, OXIMES
AND N-SUBSTITUTED HYDRAZONES BY NUCLEAR

MAGNETIC RESONANCE SPECTROSCOPY

BY

Robert Arthur Taller

A THESIS

Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of

DOCTOR OF PHILOSOPHY

Department of Chemistry

1966

To

Carol Ann

ii

3,.
r.

nL

A

-.
p“

\A‘

Stan

g

eauca

0'-
k

ACKNOWLEDGMENTS

The author wishes to express his sincere appreciation to
Professor G. J. Karabatsos for his guidance, encouragement,
and friendship during the course of this investigation.

Financial assistance from the United States Atomic
Energy Commission is gratefully acknowledged.

Appreciation is extended to his parents for their under-

standing and financial assistance during the years of his
education.

iii

 

INTRODCC

; PAR

TABLE OF CONTENTS

INTRODUCTION . . . . . . . . .
PART A--N-NITROSAMINES. .

Results. . . . . . .
Discussion . . . . .
Solvent Effects
Conformations .

syn/anti Isomers.

PART B-~OXIMES. . . . . .

Results. . . . . . .
Discussion . . . . .

Conformations of the syn Isomers. . .
Conformations of the anti Isomers . .

Chemical Shifts
Solvent Effects

syn/anti Isomers.

 

PART C--N,N-DIMETHYLHYDRAZONES AND N-METHYL-

HYDRAZONES. . . .

Results. . . . . . .
Discussion . . . . .

O O O O

Conformations of the syn Isomers. . .
The Effect of Conformations about the
Nitrogen-Nitrogen Single Bond on

Chemical Shifts and Long Range Spin
Spin Coupling Constants
StereOSpecificity

Spin Coupling

Chemical Shifts

Solvent Effects

PART D--PHENYLHYDRAZONES.

Results. . . . . . .
Discussion . . . . .

iv

of'Long

Range

Spin-

Page

15
15
20
24

26

27
45
45
52
52
56
59

6O
61

78
78

85
88
89
89
96

97
101

TABLE OF

EXPERIME

l
r
I
(

 

LITERAT

TABLE OF CONTENTS - Continued Page

EXPERIMENTAL . . . . . . . . . . . . . . . . . . . . 110
A. Preparation of N-Nitrosamines. . . . . . . . 111
Preparation of tert-Butylformamide . . . . 111
Preparation of Methyl-tert—butylamine
hydrochloride. . . . . . . . . . . . . 115
Preparation of N- -nitrosomethyl- -tert- -butyl-
amine. . . . . . . . . . . . . . . . . . 114
Preparation of Benzylacetamide . . . . . . 114
Preparation of N-Ethylbenzylamine. . . . . 115
Preparation N-nitroso-N-ethylbenzylamine . 115
B. Preparation of Aldoximes and Ketoximes . . . 116
Preparation of Cyclohexanecarboxaldehyde
oxime. . . . . . . . . . . . . . . . . . 116
Preparation of 5,5-Dimethylbutyraldehyde
oxime. . . . . . . . . . . . . . . . . . 119

C. Preparation of N-Methylhydrazones and N,N-

Dimethylhydrazones . . . . . . . . . . . . 119
Preparation of 5,5-Dimethylbutyraldehyde-
N,N-dimethylhydrazone. . . . . . . . . . 119
Preparation of Cyclohexanecarboxaldehyde-
N-methylhydrazone. . . . . . . . . . . . 122
D. Preparation of Phenylhydrazones. . . . . . . 122
E. Solvents . . . . . . . . . . . . . . . . . . 125
F. Spectra. . . . . . . . . . . . . . . . . . . 125
LITERATURE CITED . . . . . . . . . . . . . . . . . . 124

 

A:

TABLE

1.

2.

10.

11.

12.

15.

14.

LIST OF TABLES

 

Chemical Shifts (T-Values)of Nitrosamines. . .
Ao(5 cis - 6 trans) Values, in p.p.m., of Nitros-
amines . . . . . . . . . . . . . . . . . . . . .
AWN”V in benzene - W in carbon tetrachloride)

Values in c.p.s., of Nitrosamines. . . . . .

Solvent Effects on the Chemical Shifts of Methyl
Ethyl Nitrosamine. . . . . . . . . . . . . . . .

Partial Ultraviolet Spectra of Nitrosamines in
Cyclohexane. . . . . . . . . . . . . . . . . .

Chemical Shifts (T- Values) of Aldoximes and
Ketoximes. . . . . . . . . . . . . . . . . . .

Aé(é cis - é trans) Values, in p.p.m., of
Aldoximes. . . . . . . . . . . . . . . . . .

 

Aé(é cis - 6 trans) Values, in p.p.m., of
Ketoximes. . . . . . . . . . . . . . . . . . . .

AW(W in benzene - V neat) Values, in c.p.s., of
Aldoximes. . . . . . . . . . . . . . . . . . . .

A”"('V in benzene - W in carbon tetrachloride or
Neat) Values, in c.p.s., of Ketoximes. . . . . .
syn/anti Ratios and AFZOO Values for syn —%-anti
of Aldoximes . . . . . . . . . . . . . . . . .

 

syn/anti Ratios and AFZOO Values for syn —+'anti

of Ketoximes . . . . ... . . . . . . . . . . . .

Spin-S in Coupling Constants of Aldoximes (syn
isomer? at Various Temperatures. . . . . . . .

The Effect of Solvent Polarity on the Spin-Spin
Coupling Constants of Aldoximes (syn isomer) . .

vi

Page

12

14

18

19

25

52

55

56

57

58

59

4O

41

42

A5
A I

Su

a J
r/_

 

If:
nc

:0

«NO
nC

3d
9;

LIST OF TABLES - Continued

TABLE

15.
16.

17.

18.

19.

20.

21.

22.

25.

24.

25.

26.

27.

28.

29.

Rotamer Population of Aldoximes (syn isomer). .
AHO Values Obtained from Plots of log K y§ 1/T.

Spin-Spin Coupling Constants of Aldoximes (anti
isomer) at Various Temperatures . . . . . . .

The Effect of Solvent Polarity on the Spin-Spin
Coupling Constants of Aldoximes (anti isomer)

Chemical Shifts (T- Values) of Aldehyde and
Ketone N,N-Dimethylhydrazones . . . . . . . .

Chemical Shifts (T- Values) of Aldehyde and
Ketone N-methylhydrazones . . . . . . . . . .

Aé(6 gig - 6 trans) Values, in p.p.m., of

Ketone N,N-Dimethylhydrazones . . . . . . . . .
A6(6 gi§_- 6 trans) Values, in p.p.m., of alde-
hyde and Ketone N-Methylhydrazones. . . . . . .

AV(V in benzene - V in carbon tetrachloride)
Values, in c.p.s., of Aldehyde and Ketone N,N-
Dimethylhydrazones. . . . . . . . . . . . . . .

AV('v in benzene - W in carbon tetrachloride)
Values, in c.p.s., of Aldehyde and Ketone N-
Methylhydrazones. . . . . . . . . . . . . . . .

Spin~Spin Coupling Constants and Half Widths of
Aldehyde N-Methylhydrazones . . . . . . . . . .

syn/anti Ratios of Aldehyde and Ketone N-Methyl-
hydrazones. . . . . . . . . . . . . . . . . . .

 

Spin-Spin Coupling Constants of Aldehyde N,N—
Dimethylhydrazones (syn isomer) at Various
Temperatures. . . . . . . . . . . . . . . . .

The Effect of Solvent Polarity on the Spin-Spin
Coupling Constants and Half Widths of Aldehyde
N,N-Dimethylhydrazones (syn isomer) . . . . . .

Spin- Spin Coupling Constants of Aldehyde N-

Methylhydrazones (5 fly isomer) at Various
Temperatures. . . . . . . . . . . . .

vii

Page
45

44

48

49

67

69

71

72

75

74

75

75

76

76

77

LIST

mi.

25
25

IV
2v

 

 

LIST OF TABLES — Continued

TABLE

50.

51.

52.

55.

54.

55.

56.

57.

58.

59.

40.
41.
42.

45.

The Effect of Solvent Polarity on the Spin- Spin
Coupling Constants of Aldehyde N-Methylhydra-
zones (5 syn isomer). . . . . . . . . . . . .

Rotamer Population of N,N-Dimethylhydrazones
(syn isomer). . . . . . . . . . . . . . . . .

AHO Values Obtained from Plots of Log K.y§ 1/T.

Rotamer Populations of N-Methylhydrazones (fiyg
isomer) . . . . . . . . . . . . . . . . . . . .

AHO Values Obtained from Plots of log K‘yg 1/T.

Ultraviolet Spectral Values of Aldehyde and
Ketone N,N-Dimethylhydrazones . . . . . . . . .

Ultraviolet Spectral Values of Aldehyde and
Ketone N-Methylhydrazones . . . . . . . . . .

AVVV in benzene - N in carbon tetrachloride)
Values, in c.p.s., of Phenylhydrazones. . . .

Solvent Effects on the Chemical Shifts of
Butanone Phenylhydrazone. . . . . . . . . . .

Boiling Points and Melting Points of N-Nitros-
amines. . . . . . . . . . . . . . . . . . . . .

Boiling Points and Melting Points of Aldoximes.
Boiling Points and Melting Points of Ketoximes.
Boiling Points of N-Methylhydrazones. . . . .

Boiling Points of N,N-Dimethylhydrazones. . .

viii

Page

77

79

79

8O
8O

86

87

100

106

112
117
118
120

121

 

 

H
A—l

R

vv

G ,

U

T
as

F

t I _: e t t T t f. me. 3 SE S. f C I f 3 J f C J .2 L f t. E 3
.nee hmm "mm NED ...i ECSI EC( EC( Tb Es N»...
T. K «D .u . . a

.. . . . ~/. 30 Cu NO ,I ../~

n6 5 1%. :v no Is 1‘ A.‘

 

 

 

LIST OF FIGURES

FIGURE Page

1. Neat n.m.r. spectra of dimethyl nitrosamine (A),
methyl ethyl nitrosamine (B), methyl isopropyl
nitrosamine (C), and methyl tfbutyl nitrosamine
(D). . . . . . . . . . . . . . . . . . . . . . . 11

2. The upfield shift of the proton resonances of
methyl ethyl nitrosamine on dilution with
benzene. . . . . . . . . . . . . . . . . . . . . 16

5. The upfield shift of the proton resonances of
methyl ethyl nitrosamine and methyl tfbutyl
nitrosamine on dilution with benzene . . . . . . 17

4. N.m.r. spectra of Acetone (A, 10% in carbon
tetrachloride) and 2-butanone (B, neat) oxime. . 50

5. N.m.r. spectra of isopropyl methyl ketone (A,
neat) and methyl t-butyl ketone (B, 10% in car-
bon tetrachloride) oxime . . . . . . . . . . . . 51

6. AOH plot for 2-methylbutyraldehyde oxime (syn_
isomer). . . . . . . . . . . . . . . . . . . . . 50

7. Effect of solvent polarity on the Spin-Spin
coupling constant of acetaldehyde oxime (J

syn isomer). . . . . . . . . . . . . . . .HEHQ . 55
8. Effect of solvent dilution on the Spin-Spin

coupling constant of propionaldehyde oxime

(J , syn isomer). . . . . . . . . . . . . . . 54

HlHQ

9. Effect of solvent dilution on the Spin-Spin

coupling constant of isobutyraldehyde oxime

(JHiHQ/ gyn isomer). . . . . . . . . . . . . . . 55
10. The effect of benzene on the chemical shifts of

butanone oxime . . . . . . . . . . . . . . . . . 57
11. Effect of benzene dilution on the Ngfi_chemical

shift of ethyl methyl ketoxime . . . . . . . . . 58
12. Neat n.m.r. spectra of acetone (A) and 2—buta-

none (B) N,N-dimethylhydrazone . . . . . . . . . 65

ix

LIST

2O

I».
;.

E o
4 .

«WV

.45
A I

:u
;.

«J
nC

 

CL

9L
«.5

2v
AC

1.:
AC

:v
n/~

A».
A:

A:

LIST OF FIGURES - Continued

FIGURE

15. Neat n.m.r. spectrum of isopropyl methyl ketone
N,N-dimethylhydrazone . . . . . . . . . . . . .

14. Neat n.m.r. Spectra of acetone (A) and 2-
butanone N—methylhydrazone. . . . . . . . . . .

15. Neat n.m.r. Spectra of isopropyl methyl ketone
(A) and methyl tfbutyl N-methylhydrazone. . . .

16. AH0 plot for isobutyraldehyde N,N-dimethylhydra-
zone (syn isomer) . .t. . . . . . . . . . . . .

17. AH0 plot for cyclohexanecarboxaldehyde N—methyl-
hydrazone (syn isomer). . . . . . . . . . . . .

18. Effect of benzene on the chemical shifts of
acetaldehyde N-methylhydrazone. . . . . . .

19. Effect of benzene on NE and Ngfig resonances of
acetaldehyde N—methylhydrazone. . . . . . . .

20. Effect of benzene on the chemical shifts of iso-
butyraldehyde N-methylhydrazone . . . . . . . .

21. Effect of benzene on NE and Nggg resonances of
isobutyraldehyde N-methylhydrazone. . . . . .

22. Effect of benzene on the chemical shifts of
2-butanone N-methylhydrazone. . . . . . .

25. Effect of benzene on NE and Ngflg resonances of
2-butanone N—methylhydrazone. . . . . . .

24. Nuclear magnetic resonance Spectrum of 2-
butanone phenylhydrazone: A, neat; B, 5 mole
percent in benZene: C, 5 mole percent in carbon
tetrachloride . . . . . . . . . . . . . . . .

25. Effect of dilution on the chemical shifts of
butanone phenylhydrazone. . . . . . . . . .

26. Effect of dilution on the chemical shifts of
butanone phenylhydrazone. . . . . . . . . . .

27. Effect of dilution on the chemical shifts of

methyl tfbutyl ketone phenylhydrazone

Page

64

65

66

81

82

90

91

92

95

94

95

99

102

105

104

INTRODUCTION

Geometrical or configurational isomers arising from
restricted rotation about double bonds (1,2,5) and partial
double bonds (4,5,6,7) can be effectively studied by nuclear
magnetic resonance Spectroscopy (n.m.r.). A proton in group
R1 as well as in group R2, for example, may resonate at
different magnetic fields when Z is gig (I) or trans (II) to
it. AS a result of this magnetic nonequivalence two R1 Sig—

nals may be observed, one for each geometrical isomer.

Z Z
Y//’ ‘\\Y
H H
X X
R2"/ \‘R1 R2/ \R1
I (cis) II (trans)

 

The relative field position of these two Signals will vary
with X (carbon, nitrogen), Y (nitrogen, oxygen) or Z
(hydrogen, oxygen, substituted nitrogen). For example,
whereas in one particular compound R1 may resonate at a higher
field (Shielded) when gig (I) than when Egagg (II) to Z, in
another the reverse might be true (8).

Conformational isomers can be studied by observing dis-
crete changes in Spin—Spin coupling constants (9,10) and in
chemical Shifts (11). For example, the important conforma-
tions of a tetrahedral carbon bonded to a trigonal carbon may
be determined by measuring changes in the Spin—Spin coupling

constant, J with temperature and solvent. Assuming

HlHa’

Jt>Jg I12), where J is the trans coupling (dihedral angle

t
A’1800) and J9 is the gauche coupling (dihedral angle Av600),

Z Z Z
Y/ y/ Y/

\/\ , , - \‘\u
’,' H1 " ' H1 ' - 1
HOL"/ '
H
R

III IV V

the averaged coupling Should be temperature independent if
III, IV and V are energetically equivalent. If V is more
stable than III or IV, the coupling Should increase with
increase in temperature, and if it is less stable, the coupling
Should decrease (10). In the absence of Spin-Spin coupling
between protons in group R1 with protons in group R2 (I)
conformational data may be obtained from chemical Shifts.
Although this requires knowledge of the anisotropic effects of
the carbon-nitrogen and the nitrogen-nitrogen double bonds,
intelligent guesses can be made by comparison of these with
other isoelectronic groups (11,15).

Additional information regarding configurational and
conformational isomers may be obtained from the variations
of chemical Shifts (8,14,15,16,17) and to a smaller extent
coupling constants (18,19) with solvent. These variations
are generally attributed to changes in the dielectric con-
stant of the solvent (20) or to solvent association with
substrate. With respect to association two distinct inter—
actions leading to chemical shift changes can occur. One
type of interaction leads to the ”hydrogen bond shift,“

whereby the hydroxyl proton signals of alcohols (21) and

 

 

it
H.
(1’
,1
rr

C]

carboxylic acids (22) appear at lower fields when these com-
pounds are associated than when they are unassociated. This
is an example of an nfdonor association, that is, hydrogen

bonding between the lone pair electrons of the donor species

with the protons of the acceptor molecule (VI). The chemical
Shift of the unassociated species can be obtained by dilution
with an inert solvent. A second type of interaction arises
from association of a proton (15) or polar molecule (17 22 25)
with an aromatic nucleus. For example, when chloroform is
diluted with benzene (VII), the proton signal progressively
shifts toward high field as the benzene concentration in-

creases. This high field Shift can be attributed to the large

C]. O\ C /H Ti)
3 H C
c1—-—c-——c1 H/\ \c / \‘CH3
H CH3 \/ CH3 C/q
CH/K/ cs.3
VII VIII IX

induced diamagnetism resulting from circulation of the
_flfielectrons of the aromatic ring. Association between benzene
and N,N-dimethylformamide (VIII) and between benzene and

Inesityl oxide (IX) lead to similar results (22 25). These

 

.

US$215?

r. E T. . . -
. . . w L. E . . - .. .
we MW. 3 3 E q, M.» ca .5 8 TI t.
f . 1: WA. ‘1 ‘ . . ,
.B U S 1.. .1 S I t n r d O r C .4 .F. O S
i .l f .. c I S .l 3 .e n. S Q I 3. t r
a D A o .I d d n... C .w a .1 Dr 8. G O O. A

 

interactions lead to the fy-donor association shifts,” which
in most cases are upfield Shifts.
In order to understand the factors that influence:

(a) syn—anti isomerism about double bonds and partial double

 

bonds; (b) the relative stability of the conformations of a
tetrahedral carbon bonded to a trigonal carbon; (c) the
anisotropic effects of hetero-atoms bonded to a carbon-
nitrogen or nitrogen-nitrogen double bond; and (d) the effect
of solvents on chemical shifts and coupling constants, the

following systems were studied.

A. Nitrosamines. A preliminary study of three nitros-

 

amines by the author (24) showed that the previously reported
assignments (7) were incorrect. To further elucidate
nitrosamine-solvent association and to assess the important
conformations of these compounds, ten additional nitrosamines

were studied.

B. Oximes. Phillips (1) assigned structures to the_§ynl
and §n£i_forms of several oximes and concluded that the only
isolable form of aldoximes is the an£i_form. Lustig (2) re—
ported that isomers of ketoximes could only be observed in
aromatic solvents. He also postulated that magnetic non—
equivalence was due to the oxygen atom. Saita (25). on the
other hand, attributed the anisotropy of the hydroxylamino
group to the lone pair electrons of the nitrogen atom.

.A series of aldoximes and ketoximes were prepared in order

t4
.

._J

 

.wx. -4“
-
-C".

paw-Iv“, 1“.“
SUIT.

\rv‘

A.
r.
‘—
a“
C

v I
e
f

v.
nu.

we?
(X) .

V

r.

#C

(L

to understand the anisotropic contributions of the hydroxyl-
amino group and to elucidate the conformations of these
compounds. The effect of solvents on the chemical shifts and

Spin-spin coupling constants were also studied.

C. N-Methylhydrazones and N,N—Dimethylhydrazones. These
compounds were prepared in order to understand the factors

controlling syn—anti isomerism and to determine conformational

 

preference about the nitrogen-nitrogen single bond.

D. Phenylhydrazones. Although syn and anti assignments

 

were previously reported (24), the effect of solvents
(aromatic and aliphatic) on the chemical shifts that could
possibly reveal the degree and type of association in solution
was not examined.

The following conventions will be used throughout this
thesis: The 222 isomer has Z gi§_to the smaller alkyl group
(X). For example, the syn_isomer of butanone oxime has the
methyl and hydroxylamino groups gg§_to each other. The nota-
tion used to distinguish the various protons is Shown in XI,

each proton being referred to as £i§_or traps with reSpect to Z.

(Z Z
a 5
Y Y
H H
/X\ /X\
R2 R1 CHB— CHQ HI

X X I

PART A- -N-NITRO SAMINES

Results

Figure 1 Shows the n.m.r. Spectra of dimethyl, methyl
ethyl, methyl isopropyl and methyl t—butyl nitrosamines.

Table 1 summarizes the chemical shifts and syn/Anti ratios of

 

several nitrosamines. The chemical Shifts are accurate to

i 0.05 p.p.m. The accuracy in chemical shift differences
between gig and EEEEE protons is 4.0.01 p.p.m. The syn/anti
ratios were determined by integration of peak areas and are
accurate to 1.5%. The syn/gag; assignments are based on the
assumption that the ratio Ia/IIa increases as R changes from

ethyl to isopropyl to t—butyl.

6 6
Ia IIa

Two observations are pertinent to the ensuing discussion
on conformations: (a) In R(CH3)NNO the resonance of the
trangeB—methyl of the R group shifts to lower fields as R
changes from ethyl (T = 8.62) to isopropyl (T = 8.58) to
tfbutyl (T = 8.46). In R[CH(CH3)2]NNO the resonance of the

trans-armethine Shifts to higher fields by 0.5-0.4 p.p.m. as

 

R changes from methyl (T = 5.15) to benzyl (T = 5.45) to
isopropyl (T = 5.74).
Table 2 contains the differences in chemical shifts of

.gi§_and trans protons. A positive (+) A5 means that gig

bk 1'.

{58.

Y.”

 

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1.
.n
6
a

,c.

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A

we ‘1'

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AK;

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G

a .

a.
w A
Cu

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m I a
. m. L
,J

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I

l

the

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~

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C

F c

@1128}
I)

.0 t

protons resonate at higher fields than Egang; a negative re-
verse. The important points are: (a) Whereas oemethyl and
ormethylene protons resonate at higher fields when gig than
when Egan§_to the nitroso oxygen, osmethine protons resonate
at lower fields (negative A6). (b) While positive A6 values
are smaller in benzene than in carbon tetrachloride-—with di-
isopropyl nitrosamine the notable exception-~negative A6
values are larger in benzene. (c) The A5 values for armethyl,
unmethylene and B-methyl vary over small ranges, while those
for onmethine vary over larger ranges.

Table 5 summarizes AV (v in benzene -N in carbon tetra-
chloride) values obtained from the data in Table 1. The
important points are: (a) AW values are higher for the Egans
than for the gis protons, except for the B—methyl of diiso-
propyl nitrosamine which is smaller. Nitrosamines thus behave
similarly to amides (16,22,26,27,28), but opposite to compounds
having the structure R1R2C==NNHX (see Parts C and D). (b) AS
the size of R1 and R2 of dialkylnitrosamines increases the AV
values for gishdsmethine are very small and decrease as the
R of RCCH(CH3)2]NNO increases in size.

Table 4 shows the effect of various solvent on the chemical
shifts of methyl ethyl nitrosamine. Figure 2 shows the varia-
tion of the chemical Shifts of methyl ethyl nitrosamine with
ibenzene as the solvent. Figure 5 compares the effect of dilu~
‘tion on the chemical Shifts of methyl ethyl and methyl-tfibutyl

Ilitrosamine. When carbon tetrachloride or dimethyl sulfoxide

are used

 

the chemi

spectral

 

 

10

are used as solvents, dilution has practically no effect on
the chemical shifts. Table 5 contains the ultraviolet

spectral values of several nitrosamines in cyclohexane.

11

 

\
OI

 

 

 

 

 

 

 

 

 

 

 

 

 

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_ It I

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5.0 6.0 7.0 8.0 9.0 10.0 (TMS)

Eugure 1. Neat n. m. r. Spectra of dimethyl nitrosamine (A),
ethyl ethyl nitrosamine (B), methyl isopropyl nitrosamine
(C), and methyl t—butyl nitrosamine (D)-

 

 

 

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15
Discussion

Solvent Effects--The greater upfield shift of the trans
over the gig proton resonances when the solvent is changed
from carbon tetrachloride to benzene suggests stereospecific
association between benzene and the nitrosamine. Structure

IIIa, whereby the benzene is attracted by the positive charge

IIIa

on the nitrogen and repelled by the negative charge on the
oxygen, is the most attractive formulation of this associa-
tion. All the data support IIIa. For example: (a) Figure 2
shows that on dilution with benzene the ££3g§_proton shifts
upfield more rapidly than the gig, (b) Table 5 shows that
the A” values of alkyl methyl nitrosamines decrease as the
alkyl group is changed from methyl to tfbutyl. The increase
in the size of R should decrease the equilibrium constant

for ;, Figure 3 also supports structure IIIa in that the

 

RlCHgNNO + CeHe 7" RICHgNNO'CeHS 1

resonances of ethyl methyl nitrosamine shift upfield more
rapidly than those of methyl Efbutyl nitrosamine. Further

support for structure IIIa is shown in Table 4. Alkyl

16

 

 

p.p.m.

I

A0

 

 

 

 

 

O\ N\
C /
0.2— OWCHZ + CH5
‘13\.
0.0 I l l 1
10 30 50 7O 9O

Mole % EtMeNNO

Figure 2. The upfield shift of the proton resonances
of methyl ethyl nitrosamine on dilution with benzene.

 

40000000

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17

 

 

 

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A0
9
l.

01/5

H
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(C H3)3C + CH3

 

 

 

 

10 30 50 7O 90
Mole % Nitrosamine
Figure 5. The upfield shifts of the proton resonances of

methyl ethyl nitrosamine and methyl t—butyl nitrosamine on
dilution with benzene.

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substitu‘
orotons ‘

steric ij

 

Con,

 

couple t
R1 and R

tion OP t

 

simplify

of this

 

groups h
From the
samines g
that the
tatiVely
that the
to the r

CUSSiQn

20

substituted benzenesdo not shift the resonances of the trans
protons to as high fields as benzene does. On the basis of
steric interactions this trend is anticipated.

Conformations--Since the protons of R1 and R2 do not

 

couple to a measurable extent, the important conformation of
R1 and R2 must be deduced from chemical shift data. Informa-
tion on the anisotropic contribution of the NNO group could
simplify conformational assignments. However, in the absence
of this information, a comparison of the NNO group with other
groups having similar anisotropic characteristics is necessary.
From the similar behavior of the chemical shifts of the nitro—
samines and the R1R2C==NZ compounds it is reasonable to assume
that the anisotropic effects of the two groups are quali-
tatively similar. Previous work in this laboratory (24) showed
that the region in the C==NZ plane is deshielded with respect
to the region above and below the plane. The ensuing dis-
cussion of conformations will be based on the assumption that
the region in the NNO plane is also deshielded with reSpect
to the region above and below the plane.

Pertinent conformations of the gig groups can be deduced.
with some certainty, only from the isopropyl group. Of the

two conformations IVa and Va only the eclipsing structure IVa

o 6
N/ N/
H H H E CH3
/N /N x
R + ~~ ,CH R +
3
H3 CH3

on

0.00

‘?

U1

21

is consistent with the results. Conformation IVa explains
the fact that a0methine protons, compared to akmethyl and
QPmethylene, resonate at lower fields when gi§_than when trans
to the oxygen. Conformation IVa also explains the small A’V
values for the gig-armethine, because the methine is farthest
away from the associated benzene and should experience a
smaller anisotropic effect.

To deduce the conformations of the trans group two assump-
tions must be made: Firstly, that the group R eclipses the

nitrogen-nitrogen double bond VIa and secondly that region A

6 6
N/0 H/ N/
(A) H ll H \/
| N N
N \/+\R +\
./ Rig” "
R CH3

VIa VIIa VIIIa

in the plane of the NNO group is deshielded with reSpect to
region B. The first assumption is based on evidence regarding
rotational isomerism about spa-Sp3 carbon-carbon bonds (29)°
On the basis of these assumptions it will be shown that when

R is methyl VIIa is more stable than VIIIa, and that the ratio
VIIa/VIIIa decreases as R changes from methyl to isopropyl.
Considering the conformation of methyl tfbutyl nitrosamine,
IXa, of methyl isopropyl nitrosamine, Xa, XIa' and XIa", and
of methyl ethyl nitrosamine, XIIa', XIIa" and XIIIa, if Xa

is energetically comparable to XIa and XIIa to XIIIa then in

CH4]

CH3

CHO] CH3

Xa

XIIa'

22

o
N /
/"N
CH3 ’ +\CH3
CH3
IXa
6'
N/
CH3 N
’ +\CH3
H,
CH3
XIa'
'6
N /

6'
N/
003 H
N\
,4 + CH3
CH1;
H
XI I I
a
'6
N/
00. H

XIIIa

all three compounds the methyl groups should spend one-third

of the time at region A and two-thirds of the time at region B.

Therefore, the trans-B-methyls of all these compounds should

resonate at approximately the same field.

over XIa and XIIa over XIIIa,

If Xa is favored

then the methyl groups should

Spend one-third of the time at region A in the tfbutyl com-

pound IXa and progressively less than one-third in the isopropyl

and ethyl compounds.

In this case the tfibutyl should be at

25

lower field than the isopropyl and the isopropyl at lower
field than the ethyl. The data (Figure 1) adequately support
the last hypothesis.

The important conformers of the diisopropyl nitrosamine

are XIVa and XVa. Due to severe methyl interactions in XIVa

N/6 N /6
H '1le CH3 ‘N. H
CHé’)/+ \“CHa H + \““‘CH3
CH3 CH3 CH3 CH3
XIVa XVa

the ratio XVa/XIVa should be larger than the ratio XIa/Xa.
Comparison of the chemical shifts of diisopropyl nitrosamine
and methyl isopropyl nitrosamine supports this conclusion.
(a) The trans-armethine of diisopropyl nitrosamine should be
shifted upfield with respect to that of the methyl isopropyl
nitrosamine (in carbon tetrachloride the shift is 0.59 p.pom.
Table 1). The trgggrB-methyl should be shifted downfield

(in carbon tetrachloride the shift is -O.1O p.p.m.). (c) The
AV value for trangrohmethine should be larger for diisopropyl
than for methyl isopropyl nitrosamine. Table 5 shows that
the A” value for gigrarmethine decreased from 9.0 to 2.4
c.p.s. due to a decrease in complex stability, whereas the
,Egggg-armethine increased from 27.0 to 50.6 c.p.s. (d) The

AV value of the trans-fi-methyl should decrease more rapidly

24

than that of the corresponding gigffi-methyl in going from
methyl isopropyl to diisopropyl nitrosamine. Table 5 shows
that the corresponding decreases are 12.8 and 9.0 c.p.s.

The change of the transeB-methyl is large enough to result in
AV gig (21.0 c.p.s.) > A” trans (20.4 c.p.s.) for diisopropyl
nitrosamine.

Syn/anti Isomers--The syn/anti isomer ratios of nitros-
amines are comparable to those of R1R2C==NZ compounds (3).
Table 1 shows that the ethyl, benzyl and nfbutyl groups have
the same effective size. The phenyl group, on the other hand,
has a large effective size. In isomer XVIIa the loss of over-
lap is large enough to shift the equilibrium in favor of XVIa.

When R is methyl only the cis-methyl isomer is observed.

 

5 o
NI/ 7?
N :9“ N
./+\R ‘ ©/+\R
XVIa XVIIa

The possibility of rapid isomer interconversion is excluded
by the fact that both isomers are observed when R is ethyl
or isopropyl. The ultraviolet spectra (Table 5) show a de-
crease of Amax from 275 mu (R = CH3, CH2CH3) to 250 mu (R =
isopropyl). Apparently when R is isopropyl the interactions
between phenyl and isopropyl in XVIa are sufficiently large
to cause loss of overlap between phenyl and the NNO group.
The 224 mu band (R = isopropyl) could be the absorption of

isomer XVIIIa.

25

 

 

 

Table 53. Partial Ultraviolet Spectra of Nitrosamines in
Cyclohexanea

RlRlRZNNORe hmax(mu) 0 x 103
CH3 CH3 252 5.87
CH3 ‘CHECHg 255 5.79
(CH3)2CH (CH3)2CH 255 6.25
CH3 CSHS 274 7.02
CH3CH2 C6H5 275 6.77
(CH3)2CH CSHS 250 5.55

224 7.69

 

aIn 95% ethanol a hypsochromic shift occurs of about 5-5 mu.

PART B--OXIMES

26

27
Results

The n.m.r. spectra of acetone, 2-butanone, methyl iso-
propyl ketone and methyl tfbutyl ketone oximes are shown in
Figures 4 and 5. Table 6 contains the chemical shifts, which
are accurate to.i 0.05 p.p.m., of aldoximes and ketoximes.

The differences between the chemical shifts of gi§_and Egagg
protons are summarized in Tables 7 and 8. A6 Values were
obtained from the chemical shift data in Table 6. A positive
(+) A6 value means that protons resonate at higher field when
“gig than when trans to the hydroxyl group. A negative (-)
value denotes the reverse. The interesting points are:

(a) H1 resonates at lower field when gig to the hydroxyl group
than when trans. The A6 value is approximately -O.7 p.p.m.

(b) In contrast to H1,Igi§eahmethyl protons, in neat liquid or
in carbon tetrachloride solution, resonate at slightly lower
fields than or at the same field as the traps-QPmethyl protons.
The A0 value is approximately 0 to -0.05 p.p.m. The notable
exception is acetophenone, which has a A6 of -O.22 p.p.m.

(c) thethylene and ormethine protons also have negative A0
values. Generally aamethine A6 values, -O.9O p.p.m., are larger
than H1 A6 values, which are -O.7O p.p.m. (d) In every case,
Exxcept for acetophenone, A0 values are more negative in benzene
tilan in the neat liquid or carbon tetrachloride solution.

(63) B-Methyls, with the exception of di-tfbutyl ketone oxime.

lurve very small A6 values.

OI Ci
reve

shif

(17

NY

28

Tables 9 and 10 summarize AV(V in benzene - V in carbon
tetrachloride or neat) values of aldoximes and ketoximes
respectively. A positive (+) AV value means that protons
resonate at higher field in benzene than in the neat liquid
or carbon tetrachloride solution. A negative value means the
reverse. The important points are: (a) In most cases benzene
shifts both gig and trans—H1 upfield; the trans protons,
however, show a greater upfield shift than the corresponding
.gig protons. The exceptions are cyclopentanecarboxaldehyde
oxime where the gisle shifts downfield (AV = -1.2 c.p.s.),
and the Eléin of Efbutylacetaldehyde oxime (AV = 0.0 c.p.s.).
(b) The gig and trans dfimethyl protons are shifted upfield.
(c) amMethylenes have positive A” values, with tfbutylacetal-
dehyde being the notable exception, for both gig and trans
protons. trans-ahMethines have positive A'v values, whereas
.gig-armethines have negative. The gig-abmethine of isopropyl
tfbutyl ketone oxime, whose A” is +22.2 c.p.s., is the notable
exception. (e) Both the gi§_and trans B-methyl protons are
shifted upfield, except the gig-B-methyl of isopropyl_tfbutyl
ketone oxime and the trans-B-methyl of di-tfbutyl ketone oxime.

Tables 11 and 12 summarize the syn/anti isomer ratios
and the free energy differences between the two isomers-Of
aldoximes and ketoximes. There seems to be little correlation
between group size and isomer stability. In acetaldehyde oxime
the supposedly sterically unfavorable apt; isomer predominates.

Table 15 summarizes the effect of temperature on the spin-

Spin coupling constants (J

) of oxime isomers in which the
HiHa

hvdrcxy;
r 7 ‘3‘
p.ec.51_

11 can

:1";

r(j

with ace
pentanec

-33° to J

 

increase

Of tempeJ

Cf the a}

29

hydroxyl is gig to the aldehydic proton (gyn_isomer). The
precision from several measurements is about i 0.03 c.p.s.

All coupling constants decrease with increase in temperature,
with acetaldehyde oxime showing the smallest change. Cyclo—
pentanecarboxaldehyde oxime shows the largest decrease from
—300 to +900C. Table 14 shows the decrease in coupling with
increase of solvent polarity. Figures 7, 8 and 9 show the
effect of dilution on the spin-spin coupling constants of

the syn isomers of acetaldehyde, propionaldehyde and isobutyr-
aldehyde oxime respectively. Table 15 summarizes the effect
of temperature on the Spin-spin coupling constants, JHlHa’
of the §n£i_isomers i,§,, those in which the hydroxyl is

trans to the aldehydic proton. The notable differences between
JHiHa (anti) and JHchz (syn) are: (a) JHin (gag) increases
abruptly in changing from a monosubstituted to a disubstituted
acetaldehyde oxime. (b) Whereas JfllHa‘EEEE) of the disubsti-
tuted derivatives decrease with increase in temperature, those
of the monosubstituted derivatives behave erratically. (c) As
evidenced from Table 16 JHlHQ (anti) increases with increasing

solvent polarity.

50

 

 

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Table 14. The Effect of Solvent Polarity on the Spin-Spin
Coupling Constants of Aldoximes (£12 isomer).
H1 —N/9H /. ---------- JHjHa(C p.s ) '''''''''' ‘\
RlR2CH::>h Neat Cyclohexane Acetonitrile
R1 R2 (400) (40°)a (40°)a
H H 5.94 5.91 5.91
H CH3 5.85 5.79 5.74
H CH2CH3 6.10 6.11 6.09
H CH(CH3)2 6.42 6.45 6.44
H C(CH3)3 7.10 7.08 6.95
H CeHs 6.49 b 6.41
CH3 CH3 6.55 6.02 6.01
CH3 CH2CH3 7.19 6.96 6.85
CH3 (CH2)2CH3 7.58 7.15 7.05
CH3CH2 CH2CH3 8.08 7.74 7.75
CH3CH2 (CH2)3CH3 8.15 7.92 7.85
(CH3)2CH CH(CH3)2 8.42 8.18 8.08
<::7 7.12 6.86 6.89
Q 6.15 5.71 5.95

 

a10% solutions.

b

Sample insoluble in

cyclohexane.

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44

Table 16. The Effect of Solvent Polarity on the Spin-Spin
Coupling Constants of Aldoximes (anti isomer).

 

 

 

 

H1\ f- ----------- JHlHa(c.p.s.) ------------ 1
R1R2CH//-N\OH Neat Cyclogeiane Acetogitrile
(R; R2 (40°) (40°) (40°)

H H 5.51 5.55 5.68
H CH3 5.49 5.51 5.52
H CH2CH3 5.47 5.57 5.59
H CH(CH3)2 5.52 5.67 5.61
H C(CH3)3 5.82 5.82 5.95
H C6H5 5.45 b 5.56
CH3 CH3 7.55 7.22 7.24
CH3 CH2CH3 7.80 7.68 7.77
CH3 (CH2)2CH3 7.85 7.78 7.86
CH3CH2 CHgCHg 8.22 8.20 8.54
CH3CH2 (CH2)3CH3 8.51 8.26 8.56
(CH3)2CH CH(CH3)2 8.69 8.55 8.72

<::7 7.20 6.96 7.29

<:::> 7.27 7.21 7.58

 

a10% solutions.

bSample insoluble in cyclohexane.

 

oft
tati

ten}

whe:

45

Discussion

Conformations of the gyn Isomers--The relative stability

of the rotamers of the syn isomers of aldoximes can be quali-

tatively assessed from the dependence of J

(Ib) on

temperature, provided the following two assumptions are correct.

OH
N /
RZCHa/U\H1
Ib

(a) The minimum energy conformations are IIb, IIIb and IVb, Vb,

whereby a single bond eclipses the double bond. Several

OH
N /
H1 ‘
“-4 H
Hé’
R
IIb
OH
N/
H
H; H
R2
IVb

Ilb'

Vb

N,//OH
R I
I"’ H
H2
IIIb
OH
N/
R2
0" H
R1
V I

 

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sp3 to
true (9
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IIIb a:
indeper
should
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the m:
eclipg
1
be det

of ace

46

studies on rotational isomerism about single bonds joining
sp3 to a spa hybridized carbon atoms have shown this to be
true (9,10,29,50). (b) Jt > Jg (12), where Jt is the Egagg
coupling (dihedral angle = 180°) and J9 the gauche (dihedral
angle = 600). On the basis of these assumptions, if IIb and

IIIb are energetically equivalent, J should be temperature

HlHa
independent. If 11b is more stable than IIIb, this coupling
should decrease with increase in temperature; and if less
stable, it should increase. Similarly, if IVb and Vb are
energetically equivalent the coupling should be temperature
independent. If IVb is more stable than Vb, the coupling
should decrease with increase in temperature; and if less
stable, it should increase. For all the gyn isomers examined,
the most stable rotamer is the one in which the hydrogen
eclipses the double bond.

The enthalpy differences between the various rotamers may

be determined as follows. Equation_;_expresses the coupling

of acetaldehyde oxime (VIb) in terms of Jt and J9. Equation 2_

OH

 

VIb VIIb

eXpresses the couplings of the monosubstituted oximes, where X

is the fractional population of IIb and (1 - x) that of IIIb.

 

 

Equatic
where )
of Vb.
oxime c
calcul

then b

plots

Stitut
the L3
tion

(51,31
Pound

Subst

which

10g K

more

47

Jobs. = 1/5(Jt + 2J9) _1
Jobs. = x(Jt + Jg)/2 + (1 - X)Jg .2
Jobs. = XJt + (1 - x)Jg _5

Equation 5 expresses the couplings of the disubstituted oximes,
where X is the fractional population of IVb and (1 - X) that
of Vb. If it is assumed that at -5o° tfbutylacetaldehyde

t

calculated from equations_1_and_43 Rotamer populations can

oxime exists solely in conformation VIIb, J and Jg can be

then be calculated from equations_g and_§, and AH0 values from

J = 1/2(Jt + Jg) 4

obs.(tfbutyl)

plots of log K.y§ 1/T.

Use of the same Jt and J9 for monosubstituted and disub-
stituted acetaldehyde oximes would introduce some error in
the AH0 values. To minimize this error a 0.4 c.p.s. correc-
tion should be applied for each alkyl or aryl substituent
(51,52). Thus the observed coupling of monosubstituted com-
pounds should be increased by 0.4 c.p.s. and that of the di-
substituted by 0.8 c.p.s. This procedure gives Jt = 13.0
c.p.s. and J9 = 2.4 c.p.s.

Table 17 contains the rotamer populations calculated
from equations 2 and 3. Table 18 summarizes the ABC values,
which are probably reliable to.i 30%, obtained from plots of
log K.y§ 1/T (Figure 6).

The AHO values in both cyclic and acyclic series become

more positive as the alkyl group R increases in size. This

 

48

 

 

 

 

mm 00 Nd 00 00 00 AHHUV
m0 m0 om mm mm mm m V

00 mm 00 00 mm 00n00000 0000n000

mm mm 00 mm mm mm 000000000 000000

mm mm o0 00 mm 00 n00000 000n00

om am mm 00 mm 00 000000000 000

>0 00 00 00 on 00 mm mm 00 000000 000
00 00 00 00 00 mw 000 000

mm 00 mm mm mm 0000 0

mm mm mm mm 000 0000000 0

mm mm mm mm 00 00n00000 0

00 no no on 00 mm 000000 0

00 00 00 mm 00 mm 000 0
oom0 .6000 6000 hood oO0 com com oow oo oom- 00 H0
0 000000

R m 1--- Z&
r uuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuu \
J. . .. .
moxx
.0008000 cxmv 0060xo000 0o 0000005000 00E00o0 .00 00009

49

Table 18. AH0 Values Obtained from Plots of log K.y§ l/T.

 

 

 

R iRgCHCH= NOH

 

 

R1 R2 AHO (cal/mole)
H CH3 +720
H CH2CH3 +750
H CH(CH3)2 +520
H C(CH3)3 +5900
H ceHs +740
CH3 CH3 +550
CH3 CH2CH3 +510
CH3 (CH2)2CH3 +670
CH3CH2 CH2CH3 +720
CH3CH2 (CH2)3CH3 +710
(CH3)2CH CH(CH3)2 +460

0 +700
<:::> +460

 

50

.0005000 :N0v 0E0xo 00%:00000w0500mn00EIN 000 0000 000 .0 005000
maoaxa\0
m.m
_

0.0 0.0
0 _

 

 

_
10¢.OI

|

¢¢.OI

l

o0.o-

l
N
N)
O

I

l

0N.OI

10m.o-

 

 

 

51

trend parallels that observed with aldehydes (10a). The more
positive AHO value of cyclopentanecarboxaldehyde oxime over
cyclohexanecarboxaldehyde oxime may be rationalized as follows.
In the cyclopentyl case, because of less puckering of the ring
the nitrogen is closer to H2 (VIIIb) than it is in the cyclo-
hexyl case (IXb). The difference in interaction energies is

H
H

/
~':N/\ OH

 

VIIIb IXb

apparently large enough to lead to the observed result.

The decrease of the observed coupling constants on dilu-
tion with either polar or nonpolar solvents is probably caused
by the decrease in the strong intermolecular hydrogen bonding
(55,54) that exists in the neat liquid. Strong hydrogen bond-

ing should favor Xb over XIb. As the intermolecular hydrogen

_ H H
“N\ \o . >fl\ \o\

H-
0/ H\“~ / ‘OXime O/ ‘ x /

Xb XIb

bonding is decreased by dilution with solvent, the decrease in

52

the ratio Xb/XIb decreases the coupling. The effect of solvent
dilution on coupling is shown in Figures 7, 8 and 9.

Conformations of the anti Isomers--From the effect of

4.—

 

temperature on the coupling constants of the §g£i_isomers it
is evident that no quantitative conclusions regarding rotamer
stability can be drawn. A few qualitative trends, however,
are worth pointing out. For example, the abrupt increase in
coupling in going from monosubstituted to disubstituted oximes
suggests that XIIb is the most stable rotamer of the disubsti—

tuted oximes. The erratic behavior of the coupling of the

 

HO \
N HO\
N
H H\\ H
.a’” H ‘ H
H R
R
XIIb XIIIb XIVb

monosubstituted oximes indicates that in addition to XIIIb
rotamer XIVb might be present in large quantities.

Chemical Shifts--The A6 values summarized in Tables 7 and

 

8 show that protons gig to the hydroxyl group are generally
deshielded with reSpect to those that are trans. SaitS and
Nukada (25) attributed these differences to the anisotropic
effect of the lone electron pair on the nitrogen. In view of
the finding (55,56), which is consistent with other work on
similar systems (57), that XVb is the conformation of formal-

doxime, it is conceivable that the anisotropy of the lone

55

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CGSOQEOU R mESHo>

 

 

 

 

 

 

 

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mgxoflsm assumed. « :/=\:u
mcmxmsoHomu nu onz
mHHuuflsoumum O

 

 

 

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54

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(’S'd’D) p

55

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56

XVb

electron pairs on the oxygen, that are close to the gig group
protons, rather than that of the nitrogen lone pair causes
these differences. Regardless of the cause of these differ—
ences, the observed variations in A6 values, 2,3,, about zero,
-O.2 p.p.m. and -1.0 p.p.m. for ormethyl, damethylene and
armethine protons respectively, are not surprising. As pointed
out in the section on conformations, the average time spent by
each proton in various positions greatly depends on the degree
of substitution at the arcarbon.

Solvent Effects-~Tables 9 and 10, and Figure 10, show that
trans protons undergo a larger upfield shift than the corres-
ponding gig protons on dilution with benzene. Association

between benzene and oxime as in XVIb, whereby the benzene is
H H

\O \3 H\

o

N/ N/

(H) R R (H) H3C CH3 H
CH3

XVIb XVIIb XVIIIb

57

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_

 

 

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.mEonumx

ahsumfi Hmnum mo uwflfim HMUHEmLU moz map so COHuDHHU mammcmfl mo pommmm .fia musmflm

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G
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°m‘d°d

 

 

59

attracted by the positive charge on the Sp2 hybridized carbon
and repelled by the hydroxyl lone electron pairs (25), ade-
quately rationalizes this fact. The deshielding, Figure 11,
rather than the expected shielding of the hydroxyl proton,

as well as the deshielding of gigrormethine protons, XVIIb,
and gigeormethylene protons of tfbutylacetaldehyde oxime,
XVIIIb, are in good agreement with this formulation.

syn/anti Isomers-—The greater stability of XIXb over XXb

and the almost equal distribution of isomers XXIb and XXIIb

H H H
J \o o/
\N N / \N
ch/U\H ch/U\H C5H5H2C /U\H
61% 39% 45%
XIXb XXb XXIb
H
\N/
C 3H5H2C /1\H
55%
XXIIb

indicate that the attractive forces of the nonbonded inter-
actions are quite important in these, as well as in other (58),

cases .

PART C--N,N-DIMETHYLHYDRAZONES AND N-METHYLHYDRAZONES

6O

61

Results

The chemical shifts of N,N-dimethylhydrazones and N-methyl-
hydrazones are found in Tables 19 and 20, respectively. The
most apparent difference between the two is the absence of
.tgags isomers in the aldehyde N,N-dimethylhydrazone series.

The n.m.r. spectra of acetone, 2-butanone and methyl isopropyl
ketone N,N-dimethylhydrazones, are shown in Figures 12 and 15;
those of acetone, Z-butanone, methyl isopropyl ketone and
methyl t—butyl ketone N-methylhydrazones in Figures 14 and 15.
Tables 21 and 22 summarize the differences between the chemical
shifts of gig and Egagg protons of N,N-dimethylhydrazones and
N-methylhydrazones, respectively. A positive A5 value means
that protons gig to the N,N-dimethylamino or N-methylamino
group resonate at higher field than trans; a negative value
denotes the reverse, Whereas the deethyl groups of N-methyl-
hydrazones have positive A5 values, those of N,N-dimethylhydra-
zones have negative.

Tables 25 and 24 summarize the A"(N in benzene u N in
carbon tetrachloride) values of N,N-dimethylhydrazones and
N—methylhydrazones, respectively. Positive values mean that
protons resonate at higher field in benzene; negative values
denote the reverse. The important points are: (a) Av Values
are larger for N-methylhydrazones than for N,N-dimethylhydra-
zones. (b) For N-methylhydrazones the gi§_protons have con-
siderably larger AV values than the corresponding trans.

The EXB/EflEi ratios of the aldehyde and ketone N-methylhydra-

zones are summarized in Table 26.

62

Table 25 contains the spin-spin coupling constants and
half-widths of aldehyde N-methylhydrazones. The half-widths
of the app; isomers, where the N-methylamino group is trans
to the aldehydic proton, are considerably smaller than those
of the syg_isomers. The effect of temperature on the spin-

spin coupling constants, J of the syn aldehyde N,N-dim

HlHa'
methylhydrazones and N-methylhydrazones, are summarized in
Tables 27 and 29, respectively; and the effect of solvent
polarity in Tables 28 and 50. Decrease in temperature, or
increase in solvent polarity, increases these couplings.
All recorded Spin-Spin coupling values, whose precision is
about.i 0.05 c.p.s., are averages of at least three spectral
sweeps.

Tables 55 and 55 contain the ultraviolet spectral data
of N,N-dimethylhydrazones and N-methylhydrazones, respectively.
Whereas aldehyde and ketone N-methylhydrazones have similar
A and a values, aldehyde and ketone N,N-dimethylhydrazones

max

do not.

65

 

 

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Table 21.

71

Aé(6~cis - é trans)a Values, in p.p.m.,
N,N-Dimethylhydrazones

of Ketone

 

 

 

 

 

 

J
R1R2C==NN(CH3)2 cACHg) 48(CH3) N(CH3)2
R1 R2 Neat CeHe Neat CsHe Neat CsHe
CH3 CH3 -0.07 0.00 0.00 0.00
CH3 CH2CH3 -0.06 -0.03 0.00 +0.14 0.00 0.00
CH3 CH(CH3)2 -0.10 -0.06 +0.05 +0.16 0.00 0.00

 

aPositive Value means that the proton cis to the N(CH3)2 group
resonates at higher magnetic field than When trans; a negative
value denotes the reverse.

72

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Ammouzv $465 $30 Ammood Ammo? Hm Hmomzzflommam

 

 

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UCM mpmnmpHd mo ..m.m.0 CH .mmsHm> mampHCOHnomuumu COQHMU CH P I mCmNCmn CH PVPQ .wm mHQMB

75

 

 

 

 

 

 

Table 25. Spin-Spin Coupling Constant and Half Widths of
Aldehyde N-Methylhydrazones
H
Nn/NHCHs
R132CH
R1 R2 J(syn) Half width(syn) J(anti) Half Width(anti)
H H 5.58 1.55 5.67 1.05
H CH3 5.12 1.50 5.10 1.15
H C(CH3)3 6.20 1.80 5.50 1.50
CH3 CH3 5.21 1.50 5.00
CH3CH2 CH2CH3 6.50 1.50
5.00 1.45 5.50

O

 

aNeat Samples.

Table 26.

 

hydrazones

fi
—

 

—
—_

Syn/anti Ratios of Aldehyde and Ketone N-Methyl-

 

R1R2C==NNHCH3 Percent Percent
R1 R2 syn anti
H CH3 75 27
H CH2CH3 85 17
H CH2C(CH3)3 85 17
H CH(CH3)2 96 4
H CH(CH2CH3) 2 95 5
CH3 CH2CH3 85 17
CH3 CH(CH3) 2 96 4
CH3 C(CH3)3 100 0

—__

aNeat Samples.

76

Table 27. Spin-Spin Coupling Constants of Aldehyde N,N-Dimethyl-
hydrazones (syn isomer) at Various Temperatures

 

 

 

N(CH3)2 -
H1 a
:>:N JH H (c.p.s.)
R1R2CH 1 9
R1 R2 -50° 0° +440 +700
H H 5.55 5.51 5.52 5.26
H CH3 5.16 5.12 5.10 5.00
H C(CH3)2 6.24 6.24 6.22 6.11
CH3 CH3 5.55 5.25 5.12 5.08
CH3CH2 CH2CH3 6.82 6.52 6.55 6.10

< > 5.24 5.16 5.00 4.77

aNeat samples.

 

Table 28. The Effect of Solvent Polarity on the Spin-Spin Coupling
Constants and Half Widths of Aldehyde N,N-Dimethyl~
hydrazones (syn isomer)

 

 

 

H1 /N(CH3) 2
N JHlHa(C°p°S°)
R1R2CH
R1 R2 Neat- Cyclohexgne Acetonitgile Half Widthb’C
(44°) (440) (440) (c.p.s.)(440)

H H 5.52 5.50 5.57 1.79
H CH3 5.10 5.00 5.50 1.81
H C(CH3)3 6.22 6.10 6.25 1.76
CH3 CH3 5.12 4.96 5.50 1.89
CH3CH2 CH2CH3 6.55 6.24 6.80 1 .78

< > 5.00 4.80 5.50 1.90

 

a10% solutions; bNeat; CHalf width of tetramethylsilane = 0.40 c.p s.

77

 

 

 

Table 29. Spin-Spin Coupling Constants of Aldehyde N-Methyl—
hydrazones (syn isomer) at Various Temperatures
H1 NHCH3
::>=N/ JH H (c.p.s.)a
R1R2CH 1 9
R1 R2 -5o0 00 +450 +600 +600
H H 5.50 5.56 5.58 5.20
H CH3 5.55 5.15 5.12 5.10 5.05
H C(CH3)2b 6 25 6.20 6.20 6.16 6.06
CH3 CH3 5.54 5.25 5.21 5.06 4.98
CH3CH2 CH2CH3b 6.87 6.66 6.50 6.51 6.14
.b 5 20 5 15 5.00 4.95 4.88

 

aNeat samples.
Approximately 50% carbon tetrachloride.

 

 

 

 

Table 50. The Effect of Solvent Polarity on the Spin-Spin
Coupling Congtants of Aldehyde N-Methylhydrazones
(syn isomer) '
H1 NHCH3
::>=N’/ JH H (c.p.s.)
R1R2CH 1 a .
R1 R2 Neat Cyclohexage Acetonitrgle
(45°) (45°) (450)
H H 5.58 5.55 5.42
H CH3 5.12 5.06 5.24
H C(CH3)3 6.20 6.20 6.25
CH3 CH3 5.21 4.87 5.52
CH3CH2 CH2CH3 6.50 6.51 6.70
5.00 4.77 5.50

 

a
b

Spin-Spin coupling constant of acetaldehyde
10% solutions.

= 2.90

c.p.s.

78

Discussion

Conformations of the syn Isomers-~The relative stability

 

of rotamers Ic and IIc can be determined from the dependence

N CH H,CH N CH , H
/ ( 3)2( 3) / ( 3)2(H C 3)
N N

Ha \ R
," PI1 ’," H1
R H21
Ic IIc
of J on temperature, as discussed in the oxime section

HlHa
(Part B). The trans, dihedral angle = 1800, and gauche, di-

hedral angle = 600, Spin-spin coupling constants were calcu-
lated from the acetaldehyde and tfbutylacetaldehyde derivatives.

They are J = 10.6 c.p.s. and J9 = 2.7 c.p.s. for the N,N-di-

t
methylhydrazones, and J = 10.5 c.p.s. and Jg = 2.8 c.p.s.

t
for the N-methylhydrazones.

The rotamer populations of the N,N-dimethylhydrazones and
N-methylhydrazones are found in Tables 51 and 55, respectively.
The AHO values, which were obtained by plotting log K.y§ 1/T,
are listed in Tables 52 and 54. Representative plots are
shown in Figures 16 and 17. The trends in AHO values are
similar to those of the oximes. For example, aqdrdimethyl
derivatives have smaller AHO values and larger percentages of
alkyl eclipsed rotamers than the d,drdiethyl derivatives.
Similarly the AH0 values of cyclohexanecarboxaldehyde deriva-

tives are closer to those of dimethyl rather than diethyl d,dr

disubstituted derivatives.

79

Table 51. Rotamer Population of Aldehyde N,N-Dimethyl—
hydrazones (syn isomer)

H N(CH3)2 /N(CH3)2
>‘-‘N/ H N

R1R2CH _;>’,,,JL\T{
R

 

 

R1 R2 -50° 0° +44° +70°
H CH3 75 72 71 69
H C(CH3)3 99.7 99.7 99.5 97
CH3 CH3 44 45 41 40
CH3CH2 CH2CH3 62 59 56 55

42 ' 41 59 56

 

Table 52. AH0 Values Obtained from Plots of log K y_s_ 1/T

 

 

RlRZCHCH==NN(CH3)2

 

 

R1 R2 AH°(cal/mole)
H CH3 + 290
H C(CHg) 3 +4600
CH3 CH3 + 280
CH3CH2 CH2CH3 + 650

 

80

 

 

 

Table 155. Rotamer Populations of Aldehyde N-Methylhydrazones
(syn isomer)
H NHCH NHCH3
3 N//
N H /H\ 70
RIRZCH -—"" H
R
R1 R2 -50° 00 +450 +60° +80O
H CH3 76 71 71 70 69
H C(CH3)3 100 99 99 98 96
CH3 CH3 45 42 42 40 59
CH3CH2 CH2CH3 65 60 58 56 54
42 41 39 58 37

 

 

 

 

 

 

Table 54” AH0 Values Obtained from Plots of log K.y§ 1/T
///NHCH3 ’/,NHCH3
H R N
____.\......u\ ——>— H ‘

R] H H

RlRLCHCH=NNHCIia

R1 R2 A H0 (cal/mole)

H CH3 +550

H C(CHs) 3 +3900

CH3 CH3 +290

CH3CH2 CH2CH3 +560

+550

 

81

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82

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83

The effect of solvent polarity on the coupling constants
further supports the assumption that the important minimum
energy conformations are eclipsed rather than bisecting. The
observed increase of these couplings with increase of solvent
polarity fits IIIc and IVc, but not Vc and VIc. Had Vc and

VIc been the important conformations, increase in solvent

N///N(CH3)2(H.CH3) N///N(CH3)2(H,CH3)
H 51
,x” H ’,x H
H’ H’
R H
IIIc IVc

polarity would increase the ratio Vc/VIc and lead to a de-

crease in coupling, as J1200 should be smaller than Jcis'

 

N(CH3)2(H,CH3) N(CH3)2(H,CH3)

//’ N,//
(R)H\ H R (R)H |

R H

Vc VIc

The Effect of Conformations about the Nitrogen-Nitrogen
Single Bond on Chemical Shifts and Long Range Spin-Spin Cou-
,pling Constants--As mentioned, whereas of aldehyde N-methyl—
hydrazones both the syn, VIIc, and the anti, VIIIc, isomers
are present in solution, only the gyn, IXc, isomer of aldehyde

N,N-dimethylhydrazones is detectable. Furthermore, the syn

84

NHCH H c H N CH
/ 3 3 N \ / ( 3)2
N N N
R/U\H R H R H
VIIc VIIIc IXc
/N(CH3)2(H.CH3) (H,CH3) (H3C)2N\
N F
R2/U\Rl R2/]\Rl
Xc XIc

KC, and the anti, XIc, isomers of both ketone N-methyl and
N,N-dimethylhydrazones are present in solution.‘ These facts
can be explained by steric interactions that result in con-
formational preferences about the nitrogen-nitrogen single
bond. The explanation and support of it are outlined below.
Whereas both syn, XIIc, and the anti, XIIIc, isomers of
N-methylhydrazones can exist in the depicted conformations,

where the unshared pair of electrons in both isomers are

’CH3 H3» MCI—13
N/®\H H /U\ N CH3
/U\ R

R H(R') H(R') R H

XIIc XIIIc XIVc

XVc

85

parallel to and overlap with the E-orbitals of the double bond,
only the syn, XIVc, isomer of N,N-dimethylhydrazones can assume
such conformations. In the aggi, XVc, isomer, because of strong
nonbonded interactions between R and methyl, rotation about
the nitrogen-nitrogen bond might force the compound to a-con-
formation where the unshared electrons are orthogonal to the
.E-orbitals of the double bond. The ensuing loss of overlap
energy would thus explain the greater stability of XIVc over
XVc. The above explanation can be tested by ultraviolet
spectroscopy, since it implies that aldehyde N,N-dimethylhydra-
zones will have conformation XIVc and ketone N,N—dimethyl-
hydrazones conformation XVc.

The ultraviolet Spectra of aldehyde and ketone N-methyl-

hydrazones (Table 36) are similar; eflg., A ax (95% ethanol) =

m
229 mu (8 = 5.0 x 103). Aldehyde N,N-dimethylhydrazones have

239 mu (8 = 5.7 x 103). These are the

xmax (95% ethanol)
fl;-+~flf transitions. The increase from 229 mu to 239 mu is
probably due to the inductive effect of the second methyl sub-
stituent in N,N-dimethylhydrazone. In the ketone N,N-dimethyl-

hydrazone, a lower energy transition appears, which has Kmax

(cyclohexane) = 274 mu (8 = 8.2 x 102); Kmax (95% ethanol)

268 mu (8 = 8.2 x 102); and km X (H20) = 255 mu (8 = 7.8 x 102).

a
From.its solvent dependence (39) it appears to be an §_—9'flf
transition. Apparently as the lone pair electrons of the N,N-
dimethylhydrazone becomes orthogonal with the fleorbitals of

'the double bond the 1-*'£f transition shifts to lower wave-

lengths and is masked by the absorption of the solvent.

86

Table 35. Ultraviolet Spectral Values of Aldehyde and Ketone
N,N-Dimethylhydrazones

 

 

 

:—

R1R2C= NN(CH3) a Solvent xmaxmm 8
R1 R2

H CH3 Cyc lohexane 240 .8 6 .8 x 10°
H CH3 95% Ethanol 239.0 5.7x103
H CH3 H20 231.0 1.2 X 103
CH3 CH3 Cyclohexane 266.0 6.0x102
CH3 CH3 95% Ethanol 265.0 7 .6 x 102
CH3 CH3 H20 256.0 3.9 X 102
CH3 CH2CH3 Cyclohexane 274.0 8.2x102
CH3 CH2CH3 95% Ethanol 268 .0 8 .2 x 102

CH3 CH2CH3 H20 253 .0 7 . 8 X 102

 

Table 36.

87

Ultraviolet Spectral Values of Aldehyde and Ketone
N-Methylhydrazones

 

ll

 

:1R2C==NNH§:3 Solvent xmax(mu) e

H CH3 Cyclohexane 250.0 4.5x103
H CH3 95% Ethanol 228.0 4.6x103
H CH2CH3 Cyclohexane 228.0 4.1x103
H CH2CH3 95% Ethanol 229.0 5.0x103
CH3 CH3 Cyclohexane 229.0 1.9x103
CH3 CH3 95% Ethanol 226.0 4.6x103
CH3 CH3 Acetonitrile 229.0 5.5x103
CH3 CH2CH3 Cyclohexane 228.0 1.4x103
CH3 CH2CH3 95% Ethanol 228.0 4.9x103

88

Stereospecificity of Long Range Spin-Spin Coupling-—
Acetone N,N-dimethylhydrazones, conformation XVIc, shows zero
coupling between the N-methyl and the dflmethyl protons, as
judged from signal half-widths of 0.50 c.p.s. These half-
widths are the same as those of tetramethylsilane under identi-
cal instrumental conditions. When the N,N-dimethylamine group
is in conformation XIVc, then coupling between such protons
is detectable. For example, the half-width of the afimethyl
signal of acetaldehyde N,N-dimethylhydrazone, XVIIc, is 1.01
c.p.s. Since in both ketone and aldehyde N-methylhydrazones
the N-methylamino group has the same conformations as in alde-
hyde N,N-dimethylhydrazones, similar coupling are anticipated.
The half-widths recorded in XVIIIc through XXc support this

deduction.

CH3 CH3 (0.52 c.p.s.)

\-;/" <31::I'CH3
N (1.07 c.p.s.)
n/6 N/ CH3

Hsc CH3 H3C H

(0.50 c.p.s.) (1°01 C-P-So) (1.79 c.p.s.)

XVIC XVIIC
/}:f“CH3 (1.26 c.p.s.) //X:£::CH3 (1°28 c.p.s.)
N \H A H
/U\ HBC H
HSC CH3
(1.15 c.p.s.) (1.03 c.p.s.)

89

H3Cmfi.94 c.p.s.)
H N

(0.82 c.p.s.)

XXc

Chemical Shifts--The above observations concerning differ-
ences in nitrogen-nitrogen single bond conformations are
further supported by the chemical shift data. For example,
whereas the ahmethyl protons of N-methylhydrazones resonate at
higher fields when gig than when trans to the N-methylamino
group (Table 22), those of N,N-dimethylhydrazones resonate at
lower fields (Table 21).

Solvent Effects--The larger upfield shift of the gig over
the t£§n§_protons of N-methylhydrazones on dilution with benzene
(Table 24) can be interpreted in terms of XXIc. Figures 18

through 23 show the effect of solvent dilution on ketone and

’CH3
N \H\

/\
R2 R; (H)
XXIc
aldehyde derivatives. The inability of N,N-dimethylhydrazones

to form such an association complex explains the relatively

small effect of benzene on their chemical shifts (Table 23).

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PART D - - PHENYLHYDRAZ ONE S

96

97

Results

Previous studies showed that both gi§_and t£3g§_hydrogens
of phenylhydrazones resonate at higher magnetic fields in
benzene than in aliphatic solvents (24). The upfield shift
of the gig—hydrogens is, however, three to six times larger
than the correSponding trans. A comparison of the Spectra of
2-butanone phenylhydrazone, neat, in benzene and in carbon
tetrachloride is shown in Figure 24. Table 57 summarizes AW
values (AV = N in benzene - N in carbon tetrachloride) obtained
from previous work (24). The effect of various solvents on
the chemical shifts of 2-butanone phenylhydrazone is shown
in Table 58. Note that methyl benzoate, nitrobenzene, pyridine,
and 2,4-dimethylpyridine behave as nonaromatic solvents.

Figure 25 shows the effect of dilution on the gig-armethyl
and gig-B-methyl hydrogens of 2-butanone phenylhydrazone.

The dilution curves indicate that the chemical shift of the
armethyl hydrogen is more sensitive to dilution than that of
the B-methyl. Also, whereas on dilution with benzene the
chemical shifts move upfield, on dilution with carbon tetra-
chloride and dimethyl sulfoxide they move downfield. Figure 26
shows the effect of dilution on the resonances of trans-or
methyl and trans-B-methyl hydrogens° These resonances are less
sensitive to dilution than those of the gis, In contrast to
the glgfhydrogens, trans-hydrogens resonate at lower magnetic
fields when diluted with benzene. Figure 27 shows the effect

of dilution on the chemical shifts of methyl tfbutyl ketone

98

phenylhydrazone. These shifts are less sensitive to dilution

than those of 2-butanone phenylhydrazone.

 

 

 

¢HN\~

CHS’LCHlCHS

(Jr—m}
A
u’”"¢ l
N’~H¢ aaiflfiflsr ¢HN\N

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M W

A

-'\

 

 

 

 

 

 

 

 

 

 

 

| I
T = 8.0 9.0 10JO (TMS)

Figure 24. Nuclear magnetic resonance Spectrum of 2%-
butanone phenylhydrazone: A, neat; B, 5 mole % in ben-
zene; C, 5 mole % in carbon tetrachloride.

 

 

 

nmolk Com mmsHm>m

 

100

 

 

 

 

 

 

 

 

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101

Discussion

Solvent Effects--The large difference between A” (gig)
and A” (trans) (Table 57) and the dependence of the chemical
shifts on the concentration of phenylhydrazone in benzene
(Figures 25, 26, 27), can be interpreted in terms of a stereo-
specific and reversible association between benzene and phenyl-
hydrazone. The data suggest a hydrogen bonded species, whereby
the benzene molecule associates with the anilino hydrogen (Id).
Evans (40), Bottini and Nash (41) and Wepster (42) have inde-

pendently shown that the trivalent nitrogen of aniline is

Id

pyrimidal. Complex Id is consistent with all the data. For
example, since R1 is closer than R2 to the aromatic ring
center, A” (gig) is greater than A” (trans); because of steric
interaction between benzene and R1,.gis-B-methyls will assume
conformations which places them farther away than EEEFHQ from
the ring. Hence, A'v (ginga) is greater than A” (Eiifflb)-
Conformation IId can be excluded for the following

reasons: Firstly, it is not favored because of unfavorable

interactions between the phenyl group and the protons.

p.p.m.

A6,

102

 

I ‘

+0.20

+0.10‘

 

 

 

 

 

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Mole 76 EtMeC= NNHCBHS

Figure 25. Effect of dilution on the chemical shifts of
butanone phenylhydrazone: I, gig-armethyl in benzene; II,
.gig-armethyl in carbon tetrachloride; III, gigeahmethyl in
dimethyl sulfoxide; IV, gigrB-methyl in benzene; V, gig-am
methyl in dimethyl sulfoxide.

103

 

 

-0.0S

1
\
H
(D

-0.05

-O.10,

 

 

 

1 l J 1 l

O 20 4O 60 80 100

 

Mole % EtMeC= NNHC 5H5

Figure 26. Effect of dilution on the chemical shifts of butanone
phenylhydrazone: I, trans-armethyl in benzene; II, trans-or
methyl in carbon tetrachloride; III, trans-ormethyl in dimethyl
sulfoxide; IV, trans-B-methyl in benzene; V, trans-B-methyl in
carbon tetrachloride; VI, trans-B-methyl in dimethyl sulfoxide.

104

 

+0.20

+0.10 b

p.p.m.

A6,

 

 

 

l 1 l l l

l
0 20 40 60 80 100
Mole % Compound

 

Figure 27. Effect of dilution on the chemical shifts of methyl
t-butyl ketone phenylhydrazone: I, gig-ormethyl in benzene; II,
trans-B-methyl in carbon tetrachloride; III, gig-damethyl in
carbon tetrachloride; I',.gi§edrmethyl of butanone phenylhydra-
_zone in benzene; II', trans-B-methyl of butanone phenylhydrazone
in carbon tetrachloride; III', gighormethyl of butanone phenyl-
hydrazone in carbon tetrachloride.

105

R2 c\ J

IId

Secondly, if it was an important contributor, in all solvents
capable of hydrogen bonding with the anilino proton the ElfifHa
(methyl) and tran§7H0;(methyl) should be shielded by 0.5 p.p.m.
and 0.1 p.p.m., respectively (45,44). The other conformations
available by rotation about the nitrogen-nitrogen bond do not
accommodate the large A” (gi§)--AW (trans) values and are thus
discarded as important contributors.

When toluene, xylenes, or isodurene are substituted for
benzene the upfield shift of the gisfhydrogens progressively
decreases (Table 38). This can be explained as a decrease in
the stability of complex Id, i,g., the equilibrium for_1 is

greater than that for g. The data support this explanation.

R1R2=NNH¢ + CeHe ——->-E R1R2=NNH¢ - C536 1

R1R2==NNH¢ + isodurene -?-—+' R1R2==NNH¢ ; isodurene E_

For example, the resonance of the gigefia in a 1:1 (mole/mole)
mixture of benzene-isodurene (T = 8.74) is closer to that in
benzene (T = 8.77) than to that in isodurene (T = 8.65).

In solvents having two sites available for hydrogen bond-

ing with the anilino hydrogen competition is expected between

106

.H CH mum meHm> uuCooumm mHoE m COHumuquoCoum

 

 

 

 

 

 

 

>m.m mN.m ¢>.m A.E\.E .HuHV mCmHCUOmHImcmmcmm
«m.m mH.m mo.m Hw.m A.E\.E .Hqu owNConuqulmCmNCmm
em.m Ho.m mo.m ¢N.m A.E\.E .Huav mUonwHCm HanumEHQImcmNCmm
am.m am.m oa.m m«.m A.E\.e .auac mcfiwflusm-mcmucmm
mm.m mm.m A.E\.E.H"HV mCoumofiumCmNCmm
mm.m mm.m mH.m mm.m Aea\.E .H"vaCmNCmQOHOHCincmNCmm
dm.m ON.m mCoumud
mm.m OH.m mm.m mUHXOMHDm HmnumEHQ
Hm.m HH.m «o.m >m.m mCHUHumm
mm.m mm.m oo.m >H.® mCmNCmQOHUHZ
oo.o ¢H.m mo.m om.m mumoucmnamnuwm
mm.m mH.m NH.m ¢¢.m mCmNConuoHCUHQIE
mm.m ¢H.m ¢H.m mm.m waNCmQOUOH
mm.m mH.m mH.m mm.m mCmNConEOHm
mm.m 5H.m mH.m mm.m mCmNConuoHCU
mm.m ¢H.m dH.m mm.m mCmnchouosHm
mm.m ¢N.m mm.m ma.m mcHHHcmHmnmeHouz.z
mm.m mH.m mH.m mm.m mHomHCd
mm.m mH.m NN.® mm.m mCmHCUOmH
mm.m mm.m om.m o>.m mamasxum
Hm.m mm.m mm.m NH.m mamasxus
>m.m NN.m NN.m N>.m mCmHhxum
5m.m mm.m ON.m m>.m mCmCHOB
mm.m om.m om.m n>.m mCmNCmm
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.Illmmoumlll mmoto

mcommup>CchmCm mCOCmusm mo muMHCm HMUHEmCU mCu Co mmuowmum qu>Hom .mm mHQma

107

.E-donor and n—donor association. From the parallel behavior
of nitrobenzene, methyl benzoate, and pyridine to that of
acetone, dimethyl sulfoxide, and methanol (Table 38) it is
concluded that association occurs with the lone electron pairs
of the heteroatoms rather than with the grelectrons of the
rings. IIId and IVd predict no shielding of the gigfhydrogens

by the aromatic ring current.

CBHS CBHS
N/ N)
N/ \H\‘ N/ \m-

A \“N‘\ \) /U\ \“02NC6HS
R2 R1 / R2 R1

IIId IVd

Halobenzenes compete more effectively than benzene for
the anilino hydrogen, as judged by the fact that in a 1:1
(mole/mole) mixture of benzene-chlorobenzene the resonance of
.SléfHa_(T = 8.65) is closer to that in chlorobenzene (T = 8.55)
than to that in benzene (T = 8.77)° Thus hydrogen bond forma-
tion occurs at the halogen atom site rather than with the
.E—electrons of the ring. In contrast to pyridine and nitro-
benzene, the halobenzenes strongly shield the gig-hydrogens.
This difference is anticipated, as seen by comparing IIId and

IVd with Vd.

Vd

108

The strong solvent dependence of the gig: oz'resonance
in pure as well as in mixed solvents provided a measure of
the relative solvent basicity towards the anilino proton.
The relative strengths of these hydrogen bonds for the solvents
examined are: dimethyl sulfoxide > acetone > pyridine >
nitrobenzene > chlorobenzene > benzene > isodurene.

From the dilution results (Figures 25,26,27) and the above
discussion, VId is suggested as the general structure of

liquid phenylhydrazones. Structure VId explains the larger

VId

upfield shift of gi§_over transfhydrogens and of gig-Hq,over
gisfHB with increase in the concentration of phenylhydrazone
in aliphatic solvents. It also accommodates the unusual down-
field shift of Egaggrhydrogens in benzene, since the two phenyl
groups will exert a stronger shielding effect than a single
benzene ring (Id).

The shapes of the dilution curves indicate that whereas
hydrogen bonding between dimethyl sulfoxide and phenylhydra—

zone is stronger than phenylhydrazone self-association, hydrogen

109

bonding between carbon tetrachloride or benzene with the

phenylhydrazone is weaker. The sharper change in the chemi-

cal shift of Z-butanone phenylhydrazone as compared to that

of methyl tfbutyl ketone phenylhydrazone (Figure 27) implies

that increase in the size of R2 weakens self-association

(VId) and favor solvent competition for the anilino hydrogen.
Cyclic dimers and trimers that are alternative structures

to VId are not consistent with the data. For example, VIId

VIId VIIId

predicts that in aliphatic solvents increase in the concen-
tration of phenylhydrazone should lead to stronger shielding
of trans rather than gigehydrogens. Structure VIIId, which
has the same severe steric interactions as IId, is excluded

by the results from dilution studies.

EXPERIMENTAL

110

111

A. Preparation of N-Nitrosamines

Most of the nitrosamines were prepared from commercially
available amines. N-nitrosodimethylamine and N-nitroso—N-
phenylbenzylamine were purchased from Eastman Organic Chemi—
cals.

Amines were obtained from the following sources: methyl—
n—butylamine, diisopropylamine, N—isopropylaniline, N-methyl-
benzylamine, methylisopropylamine from K & K Laboratories,
Inc.; N-isopropylbenzylamine from Aldrich Chemical Co., Inc.;
methylethylamine hydrochloride, benzylamine from Eastman
Organic Chemicals; tert—butylamine, N-ethylaniline from
Matheson Coleman & Bell.

Methyl-tert-butylamine and N-ethylbenzylamine were pre—
pared by lithium aluminum hydride reduction of tert-butyl—
formamide and benzylacetamide. Since the nitrosamines were
prepared by well-known methods (45,46), only a limited

number of synthetic procedures are described. Table 39 con-

tains the boiling and melting points of the N-nitrosamines.

Preparation of tert-Butylformamide. To a 500-ml.,
three-necked, round-bottomed flask equipped with a Tru—bore
stirrer, reflux condenser and pressure equalized dropping
funnel was added 50 g. (0.41 mole) of tert-butylamine and 70
ml. of m-xylene. The flask was placed in an ice bath and
18 g. (0.58 mole) of formic acid (98%) was added dropwise
over a thirty minute period. When the addition was completed

the ice bath was replaced by a heating mantle and the material

112

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.mw mUCmemmu EOHM 05Hm> musumnmquQ

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oma .m.e .mmanama
odomumma

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m1.aa pasv mmfi

mmuem .m.s

1.52 m.ov 4m

A.ae H.ov m.mm
1.25 5.0HV wmum.mm
1.55 w.av m.~m-m.mm
1.25 m.ov «Hum.mH
1.85 H.ov m.mmumm
54.84 .m.&

1.55 m.ac mmuem
“.25 0.6V 56

1.25 o.mv mmum.mm
1.25 n.mv m.ma

mCHEmHmqunahCmnmlzIOmonuHClz
mCHEmHMNCmQH>QOHm0mHIzlomouuHClz
mCHEmHhquQHwaumlzlomouuHClz
mCHEmHmquthsumEuzIOmouuHClz
mCHHHCMammoumomHIZTOmouuHClz
mCHHHCmHmnumIZIOmouuHCuz
mCHHHCmHMCumEIzIomouuHClz
mCHEmawmonmomHHUOmouuHCIz
mCHEmHhuSQquwulahnumEOmouuHCIz
mCHEmHhuCQIClamnumEOmouuHClz
mCHEmHmmoumomHahsquOmouuHClz
wCHEmHhaumahnumEOmOHUHCIZ

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o o .uHa

mCHEmmOHUHClz

 

mmCHEmmOHUHan mo muCHom

mCHuHmE UCm muCHom mCHHHom .mm mHQma

115

was then heated to reflux. After overnight reflux the re-
action mixture was allowed to cool to room temperature.

A water trap was then inserted between the condenser and the
flask to collect the water carried over with the refluxing
xylene. When approximately 10 ml. of water was collected,
the remaining xylene and unreacted formic acid were removed
under vacuum. No attempt was made to purify the tert-butyl-
formamide. The yield of crude tert-butylformamide was 50.0

g. (80%); reported (45) b.p. 650 (1 mm.).

Preparation of Methyl-tert-butylamine hydrochloride.
Into a two liter, three-necked, round-bottomed flask fitted
with a reflux condenser, Tru-bore stirrer and pressure
equalized dropping funnel was placed 48.0 g. (1.25 mole) of
lithium aluminum hydride and 600 ml. of anhydrous ethyl ether.
The flask was then placed in an ice bath and a drying tube
was attached to the top of the condenser to eliminate moisture.
To the rapidly stirred mixture was added during a one hour
period, a solution of 50.0 g. (0.50 mole) of tert-butyl-
formamide in 100 ml. of anhydrous ethyl ether. After the ad-
dition was completed the grey suSpension was stirred overnight
at room temperature and then held at reflux for six hours.
Work-up consisted of adding 40 ml. of water, followed by 200
ml. of 2N sodium hydroxide to the cooled solution. The ether
layer was decanted from the white solid and dried over an-
hydrous magnesium sulfate. Anhydrous hydrogen chloride was

then bubbled through the dried ethyl ether extract until all

114

the amine hydrochloride precipitated (1 hour). The white solid
was filtered and dried under vacuum. The yield of methyl-tert-
butylamine hydrochloride was 29.5 g. (80%), m.p. 251°; reported

(45), m.p. 252-2540.

Preparation of N—nitrosomethyl-tert—butylamine. A solu-

 

tion of 29.5 g. (0.24 mole) of methyl-tert-butylamine hydro-
chloride, 25 ml. of glacial acetic acid and 53 ml. of water
was added to a 500-ml., three-necked, round—bottomed flask
fitted with a reflux condenser, Tru—bore stirrer and pressure
equilized dropping funnel. To the stirred reaction mixture
45.5 g. (0.66 mole) of sodium nitrite dissolved in 76 ml. of
water was added over a thirty minute period. During the ad-
dition the reaction mixture was maintained at 25-500. After
stirring at room temperature for thirty minutes, 90 ml. of
10 N sodium hydroxide was added to the cooled solution. The
material was extracted with five 10 ml. portions of ethyl
ether, dried over anhydrous magnesium sulfate and concen-
trated. Fractionation yielded a yellow liquid, b.p. 57—580

(1.5 mm.), 18.56 g. (67%); reported (45), b.p. 660 (5 mm.).

Preparation of Benzylacetamide. Freshly distilled benzyl—

 

amine (15.0 g., 0.14 mole) and reagent grade glacial acetic
acid were refluxed for four hours in a 100-ml. round—bottomed
flask fitted with a four inch air condenser wrapped with
asbestos tape. Distillation of the white semi-solid yielded
a white solid, b.p. 119-121 (0.6 mm.). m.p. 61—620, 7.42 g.

(56%): reported (47), m.p. 60.4—61.40.

115

 

Preparation of N-Ethylbenzylamine. Into a 500—ml.,
three-necked, round—bottomed flask fitted with a reflux con—
denser, Tru—bore stirrer and pressure equilized dropping
funnel was placed 5.79 g. (0.10 mole) of lithium aluminum
hydride and 200 ml. of anhydrous ethyl ether. To the stirred
mixture, cooled in an ice bath, was added 7.40 g. (0.049 mole)
of benzylacetamide dissolved in 100 ml. of anhydrous ethyl
ether. After the addition was completed, the mixture was
refluxed for 16 hours. The reaction mixture was hydrolized
with 10 ml. of water followed by 50 ml. of 2 N sodium hydroxide.
The amine was extracted with ethyl ether and dried over ane
hydrous magnesium sulfate. Anhydrous hydrogen chloride was
bubbled through the anhydrous ether solution yielding a white

solid, m.p. 164°, 6.60 g. (88%); reported (48), m.p. 184°.

Preparation N-nitroso-N-ethylbenzylamine. A solution of
6.80 g. (0.04 mole) of N-ethylbenzylamine hydrochloride and
15 ml. of glacial acetic acid was added to a 100-ml., three-
necked, round-bottomed flask equipped with a Tru-bore stirrer,
reflux condenser and a pressure equalized dropping funnel.
To the stirred mixture was added 8.50 g. (0.12 mole) of
sodium nitrite dissolved in 20 ml. of water. The pot tempera—
ture was maintained below 100 during the addition. The mix-
ture was then stirred at room temperature for three hours,
cooled (ice bath), neutralized with 50 ml. of 10 N sodium
hydroxide, extracted with ethyl ether, and dried over an-
hydrous potassium carbonate. Fractionation yielded a yellow

liquid, b.p. 89.5 (0.7 mm.). 4.0 g. (67%).

116

B. Preparation of Aldoximes and Ketoximes

 

Oximes were prepared by reacting the freshly distilled
aldehyde or ketone with hydroxylamine hydrochloride and a
suitable base (50). A large number of aldehydes and ketones
were commercially available materials. 5-Methyl-2-isopropyl-
butyraldehyde, cyclopentane carboxaldehyde and 5,5-dimethyl-
butyraldehyde were prepared in this laboratory (51). F'
Acetaldehyde oxime and 2-butanone oxime were purchased from g
Matheson Coleman & Bell. Acetophenone, and 2-methylpropional-

dehyde oximes were purchased from Eastman Organic Chemicals.

 

2,4,4-Trimethyl-5-pentanone and 2,2,4,4-tetramethyl-5-pentanone
oximes were obtained from Merck Sharp & Dohme Research Lab.

Two oxime preparations are described below. Tables 40
and 41 summarize the melting and boiling points of the

aldoximes and ketoximes.

Preparation of Cyclohexanecarboxaldehyde oxime. Into

 

a 500-ml. round-bottomed flask equipped with a reflux con-
denser were placed 10.0 g. (0.14 mole) of hydroxylamine
hydrochloride, 40.0 g. (0.70 mole) of potassium hydroxide
pellets and 200 ml. of 95% ethanol. Cyclohexanecarboxaldehyde
(10.0 g., 0.08 mole) was then added dropwise via the con-
denser. The reaction mixture was heated and maintained at
reflux for 1.5 hours. The solution was then poured onto ,

250 ml. of water, extracted with ethyl ether and dried over

anhydrous potassium carbonate. Fractionation yielded a

117

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A.EE m.HV oblmw
A.EE w.HV mm
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A.EE owv omlmw
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mm.mm m.mmumm .m.E mpmnmUHmumomHhCmnm
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118

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119
colorless liquid, b.p. 69-75 (2.6 mm.), 7.47 g. (74%).

Preparation of 5,5-Dimethylbutyraldehyde oxime. Into a
50-ml. round-bottomed flask fitted with a reflux condenser
were placed 2.5 g. (0.059 mole) of hydroxylamine hydrochloride,
10 ml. of 10% sodium hydroxide and 1.0 9. (0.0096 mole) of
5,5—dimethylbutyraldehyde. The reaction mixture was refluxed
for 11 hours, cooled, saturated with sodium chloride, ex-
tracted with three 10 ml. portions of ethyl ether, and dried
over magnesium sulfate. Fractionation yielded a colorless
liquid, b.p. 60 (15 mm.), 0.71 g. (62%).

C. Preparation of N-Methylhydrazones and
N,N—Dimethylhydrazones

 

 

A modified procedure of Braddock and Willard (52) was
used to prepare the substituted hydrazones. When pure,
hydrazone derivatives are colorless pungent smelling liquids.
Analysis (n.m.r., u.v.) of the low molecular weight aldehyde
N-methylhydrazones must be completed immediately after their
preparation, since they turn yellow and then form crystals
on standing in the refrigerator. Aldehyde hydrazones are
known to dimerize at room temperature (55). Tables 42 and
45 summarize the boiling points of the N-methylhydrazones
and N,N—dimethylhydrazones. The two preparations given below

illustrate the procedure used.

Preparation of 5,5-Dimethylbutyraldehyde—N,N—dimethyl-

 

hydrazone. Into a 25-ml., two-necked, round—bottomed flask

 

 

120

Table 42. Boiling Points of N—Methylhydrazones

 

 

Carbonyl Compound Obs. b.p. ° C
Acetaldehyde 104
Propionaldehyde 110-111
5,5—Dimethylbutyraldehyde 70 (25 mm.)
2-Methylpropionaldehyde 150—151
2-Ethy1butyraldehyde 98 (50 mm.)
Cyclohexanecarboxaldehyde 70 (4 mm.)
Acetone 116
2-Butanone 129
5-Methyl-2-butanone 140

5,5—Dimethyl-2-butanone 50 (20 mm.)

 

 

121

Table 45. Boiling Points of N,N-Dimethylhydrazones

 

Carbonyl Compound Obs. b.p. O C
Acetaldehyde 91.5
Propionaldehyde 111—112
5,5—Dimethylbutyraldehyde 65 (50 mm.)
2—Methylpropionaldehydr 108
2-Ethylbutyraldehyde 148-152
Cyclohexanecarboxaldehyde 78 (6 mm.)
Acetone 79

2—Butanone 115

5—Methyl-2-butanone 65-68 (60 mm.)

 

122

with a reflux condenser, drying tube and rubber syringe cap
was added 5.0 g. (0.05 mole) of barium oxide, and a solution
of 1.0 g. (0.01 mole) of 5,5-dimethylbutyraldehyde in 10 ml.

of absolute ethanol. To the cooled solution 1.0 g. (0.016
mole) of dimethylhydrazine was added with a hypodermic syringe.
After the initial exothermic reaction subsided, the reaction
mixture was refluxed for one hour. The material was then
cooled, filtered, extracted with additional ethanol and dried
over anhydrous magnesium sulfate. Fractionation yielded a

colorless liquid, b.p. 65 (50 mm.), 0.80 g. (56%).

Preparation of Cyclohexanecarboxaldehyde-N-methylhydra-
.5933. Into a 25—ml., two-necked, round-bottomed flask fitted
with a reflux condenser, drying tube and a rubber syringe cap
was added 7.6 g. (0.05 mole) of barium oxide and a solution
of 0.92 g. (0.02 mole) of methylhydrazine in 5 ml. of anhydrous
ethyl ether. A solution of 1.96 g. (0.02 mole) of cyclohexane-
carboxaldehyde in 5 ml. of ethyl ether was added with a hypo-
dermic syringe. The reaction mixture was allowed to stand
overnight, filtered, extracted with ethyl ether and dried over
anhydrous magnesium sulfate. Distillation yielded a yellow

liquid, b.p. 70 (4 mm.), 1.2 g. (47%).

D. Preparation of Phenylhydrazones
2-Butanone phenylhydrazone, b.p. 106-107 (2.2 mm.) and
5,5-dimethyl—2-butanone phenylhydrazone, b.p. 96 (0.7 mm.)

were prepared according to well-known procedures (54.55).

125

E. Solvents

 

Benzene-d6 was purchased from Merck Sharp & Dohme of
Canada Limited. Carbon tetrachloride, benzene and cyclo-
hexane were purified by well-known procedures (54,55).
Acetonitrile and dimethylsulfoxide were dried over calcium
hydride and distilled. All purified solvents were stored

over molecular sieves in glass stoppered bottles.

F. Spectra

Nuclear magnetic resonance spectra were determined at
60 Mc. on a Varian Associates Model A—60 Analytical Spec-
trometer. Undegassed samples were run in thin walled glass
A-60 tubes using tetramethylsilane as the internal reference.
Coupling constants (J values) were recorded at 50 c.p.s.
sweep width. Recorded coupling constants are the average of
at least three Spectral sweeps taken from low to high field
strength and vice versa. Temperature studies were carried
out using a Varian Associates V—6040 Variable Temperature
Controller. Temperatures are accurate to i.2° C. Ultraviolet
Spectra were taken on a Cary 14 Recording Spectrophotometer

(Applied Physics Corporation).

LITERATURE C ITED

124

(1)
(2)
(5)

(4)
(5)

(6)

(7)

(8)

(9)
(10)

125

W. D. Phillips, Ann. N. Y. Acad. Sci., 70, 817 (1958).

 

E. Lustig, J. Phys. Chem., 65, 491 (1961).

G. J. Karabatsos, F. M. Vane, R. A. Taller and N. Hsi,
J. Am. Chem. Soc., 86, 5551 (1964).

W. D. Phillips, J. Chem. Phys., 25, 1565 (1955).

L. H. Piette, J. D. Ray and R. A. Ogg, Jr., J. Chem. Phys.,
26, 1541 (1957).

 

W. D. Phillips, C. E. Looney and C. P. Spaeth, J. Mol.
Spectry., 1, 55 (1957).

C. E. Looney, W. D. Phillips and E. L. Reilly, J. Am.
Chem. Soc., 79, 6156 (1957).

G. J. Karabatsos, R. A. Taller and F. M. Vane, J. Am.
Chem. Soc., 85, 2526 (1965).

 

R. J. Abraham and J. A. Pople, Mol. Phys., 5, 609 (1960).

a) G. J. Karabatsos and N. Hsi, J. Am. Chem. Soc.,
87. 2864 (1965).

b) S. Mizushima, T. Shimanouchi, T. Miyazawa, I. Ichishima,
K. Kuranti, I. Nakagawa, and N. Shido, J. Chem. Phys.,
21, 815 (1955). .

c) I. Nakagawa, I. Ichishima, K. Kuratani, T. Miyazawa,

T. Shimanouchi, and S. Mizushima, ibid., 20, 1720 (1952).

d) A. Miyake, I. Nakagawai T. Miyazawar I. Ichishima,

T. Shimanouchi, and S. Mizushima, Spectrochim. Acta,
15. 161 (1958).

e) S. Mizushima, T. Shimanouchi, I. Ichishima, T. Miyazawa,
I. Nakagawa, and T. Araki, J. Am. Chem. Soc., 78,

2058 (1956).

f) R. W. Kolb, C. C. Lin, and E. B. Wilson, Jr., J. Chem.
Phys., 26, 1695 (1957).

g) S. S. Butcher'and E. B. Wilson, Jr., ibid., 40, 1671
(1964).

h) K. M. Sinnot, ibid., 54, 851 (1961).

i) C. Romers and J. E. G. Creutzberg, Rec. trav. chim.,

75, 551 (1956).

j) L. S. Bartell, B. L. Carroll, and J. P. Guillory,
Tetrahedron Letters, 15, 705 (1964).

k) E. B. Whipple, J. H. Goldstein, and G. R. McClure,

J. Am. Chem. Soc., 82, 5811 (1960).

l) E. B. Whipple, J. Chem. Phys., 55, 1059 P1961).

m) A. A. Bothner-By and C. Naar-Colin, J. Am. Chem. Soc.,
85, 251 (1962).

n) D. R. Herschbach and L. C. Krishner, ipig,, 28, 728
(1958).

 

 

 

 

(11)

(12)

(15)

(14)

(15)

(16)

(17)

(18)

(19)

(20)
(21)
(22)

(25)

(24)

(25)
(26)

(27)

(28)
(29)

126

 

 

R. M. Hammaker and B. A. Gugler, J. Mol. Spectry.,
17. 556 (1965).

M. Karplus, J. Chem. Phys., 50, 11 (1959).

H. W. Brown and D. P. Hollis, J. Mol. Spectry.,

 

15. 505 (1964).

A. A. Bothner-By and R. E. Glick, J. Chem. Phy§,,

 

 

26. 1651 (1957).

L. W. Reeves and W. G. Schneider, Can. J. Chem.,
55, 251 (1957).

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