POTASSIUM
FLUORIDE
A S A BASE IN O R G A N I C
S O L U B I L I Z E D BY
A
REACTIONS
18-CROWN-6
THESIS
Presented
to
The F a c u l t y of
the
D i v i s i o n of G r a d u a t e
Studies
by
T h o m a s Ray
In P a r t i a l
Henson
Fulfillment
of the R e q u i r e m e n t s
M a s t e r of Science
Georgia
for the
in
I n s t i t u t e of
March,
1975
Degree
Chemistry
Technology
POTASSIUM
FLUORIDE
AS A B A S E IN O R G A N I C
S O L U B I L I Z E D BY
REACTIONS
18-CROWN-6
Approved:
Charles Liotta,
Chairman
in^/ G r o v e n s t e i n
D a t e a p p r o v e d by C h a i r m a n
£ UJgyuly 11*75
ACKNOWLEDGMENTS
The author w i s h e s
to e x p r e s s his a p p r e c i a t i o n
to his
r e s e a r c h d i r e c t o r , D r . C. L. L i o t t a , for the s u g g e s t i o n
this r e s e a r c h p r o b l e m and for his g u i d a n c e and
throughout
of
encouragement
the course of this w o r k .
The author a l s o w i s h e s
Drs. E. Grovenstein
to e x p r e s s his a p p r e c i a t i o n
and L. Zalkow for r e a d i n g this
The D e p a r t m e n t
of C h e m i s t r y
is g r a t e f u l l y
for f i n a n c i a l s u p p o r t , as w e l l a s . D r . C. L.
Finally,
the author e x p r e s s e s
m a d e this w o r k
possible.
and
thesis.
acknowledged
Liotta.
a s p e c i a l word
to his w i f e , Sandy, w h o s e u n d e r s t a n d i n g
to
of
thanks
encouragement
iii
T A B L E OF
CONTENTS
Page
ACKNOWLEDGMENTS
ii
L I S T OF T A B L E S
iv
L I S T OF I L L U S T R A T I O N S
SUMMARY
Chapter
I.
v
vi
INTRODUCTION
1
Condensation Reactions
P o t a s s i u m F l u o r i d e as a Base
Crown E t h e r s
II.
EXPERIMENTAL
13
Chemicals
18-Crown-6 S y n t h e s i s
Michael Condensations
Alkylations
18-Crown-6 Complexes
III.
RESULTS AND DISCUSSIONS
47
Michael Condensations
Knoevenagel Condensations
Alkylations
18-Crown-6 C o m p l e x e s
IV.
V.
CONCLUSIONS
66
RECOMMENDATIONS
67
BIBLIOGRAPHY
68
iv
LIST OF
TABLES
Table
Page
1.
Solubility
2.
M i c h a e l C o n d e n s a t i o n s Initiated by P o t a s s i u m
in the P r e s e n c e and A b s e n c e of 18-Crown-6
3.
4.
5.
6.
of KF by
18-Crown-6
at 2 5 ° C
Solubility of KF in A n h y d r o u s E t h a n o l s
per m o l e of e t h a n o l
48
Fluoride
49
(moles of
salt
54
K n o e v e n a g e l C o n d e n s a t i o n s Initiated by P o t a s s i u m
F l u o r i d e in the P r e s e n c e and A b s e n c e of 1 8 - C r o w n - 6 .
A l k y l a t i o n s Initiated by P o t a s s i u m F l u o r i d e
P r e s e n c e and A b s e n c e of 18-Crown-6
E l e m e n t a l A n a l y s i s of
18-Crown-6 C o m p l e x e s
in
. 56
the
59
62
LIST
OF
ILLUSTRATIONS
gure
O v e r v i e w of C y a n o g e n B r o m i d e / 1 8 - C r o w n - 6
Complex
S i d e v i e w of C y a n o g e n B r o m i d e / 1 8 - C r o w n - 6
Complex
vi
SUMMARY
Heterogeneous
r e a c t i o n s w e r e carried out in w h i c h
tassium
fluoride was solubilized
in the p o l a r and
aprotic
s o l v e n t s , a c e t o n i t r i l e and b e n z e n e , in the
and a b s e n c e of 1 8 - c r o w n - 6 , a s o l u b i l i z i n g
sium s a l t s .
The r e a c t i o n s
ants w i t h a c r y l o n i t r i l e
nonpolar
presence
for p o t a s ­
studied w e r e selected
K n o e v e n a g e l , and a l k y l a t i o n r e a c t i o n s .
tions e t h y l c y a n o a c e t a t e
agent
Michael,
In the M i c h a e l
and d i e t h y l m a l o n a t e w e r e the
and e t h y l a c r y l a t e
In the K n o e v e n a g e l r e a c t i o n s
the
the same r e a c t a n t s
reac­
react-
substrates.
as the
Michael
r e a c t i o n s w e r e used w i t h the i n c l u s i o n of m a l o n o n i t r i l e
benzaldehyde
as the s u b s t r a t e .
as a s u b s t r a t e
reactant
for one
reaction.
out w i t h d i e t h y l m a l o n a t e
crown-6 present
W i t h only c a t a l y t i c q u a n t i t i e s
the r e a c t i v i t y
base was enhanced.
of the f l u o r i d e
The r e a c t i o n
tions w i t h no 1 8 - c r o w n - 6 .
the
to r e a c ­
The p r o d u c t y i e l d s w e r e a l s o
com­
synthetic methods.
Three unique complexes with 18-crown-6 were also
C y a n o g e n b r o m i d e , m a l o n o n i t r i l e , and
w a s found to form two to one
io­
of 1 8 -
times w e r e s h o r t e r and
to y i e l d s o b t a i n e d by other
the
anion as a
p r o d u c t y i e l d s w e r e b e t t e r or at least e q u i v a l e n t
lated.
as
and b e n z y l b r o m i d e , b e n z y l c h l o r i d e , and m e t h y l
d i d e as s u b s t r a t e s .
parable
and
C y c l o h e x a n o n e w a s a l s o used
in the K n o e v e n a g e l r e a c t i o n s
T h e a l k y l a t i o n s w e r e carried
po­
iso­
succinonitrile
(nitrile to 1 8 - c r o w n - 6
molar
vii
ratio)
complexes.
Of t h e s e ,
t h e m a l o n o n i t r i l e and
n i t r i l e c o m p l e x e s were t h e most s t a b l e m e l t i n g a t
and 8 3 - 8 4 ° C , r e s p e c t i v e l y .
Small s h i f t s
succino129-130°C
in the infrared
g i o n of t h e n i t r i l e m o i e t y was n o t e d w i t h c o m p l e x a t i o n ,
re­
as
1 o
well a s , small s h i f t s
t r i l e moieties with
in the
J
C-NMR f o r 1 8 - c r o w n - 6 and n i ­
complexation.
CHAPTER
I
INTRODUCTION
Condensation
Reactions
The K n o e v e n a g e l c o n d e n s a t i o n w a s i n i t i a l l y
concerned
w i t h the r e a c t i o n of f o r m a l d e h y d e w i t h a c t i v e m e t h y l e n e
nucle­
ophiles
in the p r e s e n c e of b a s i c c a t a l y s t s y i e l d i n g b i s
prod­
u c t s as
(I).!
In 1896 K n o e v e n a g e l r e p o r t e d e t h y l
acetoace-
,CH(COOEt)
CH 0 + 2CH (COOEt)
2
2
)
2
CH
(1)
2
^^CH(COOEt)
(I)
tate and b e n z a l d e h y d e
at low t e m p e r a t u r e s
condensed
to yield
in the p r e s e n c e of
ethyl
piperdine
benzylideneacetoacetate
2
(II)
.
The scope and u t i l i t y of the K n o e v e n a g e l
condensation
C H C H O + C H (COCH ) COOEt — > C ^ (H) C=C (COCH ) COOEt + H 0
6
5
2
3
3
(2)
2
(ID
has since been
expanded.
The K n o e v e n a g e l c o n d e n s a t i o n
tion of a c t i v e m e t h y l e n e
brought
pounds
drawing groups, usually
as the
compound w i t h k e t o n e s or
about by b a s i c c a t a l y s i s .
are c h a r a c t e r i z e d
is d e f i n e d
aldehydes
The active m e t h y l e n e
by the p r e s e n c e of
two.
reac­
com­
electron-with­
The m o s t common
activating
2
g r o u p s arc the c y a n o , n i t r o , a c y l , and c a r b o a l k o x y .
g r o u p s are n e c e s s a r y
to i n c r e a s e the a c i d i t y of the
g r o u p by p r o v i d i n g r e s o n a n c e
jugate b a s e .
These
methylene
s t a b i l i z a t i o n of the a n i o n i c
T h e p r i m a r y p r o d u c t of the c o n d e n s a t i o n
ally an u n s a t u r a t e d
compound, although
con­
is u s u ­
in some c a s e s a M i c h a e l
c o n d e n s a t i o n can o c c u r w i t h an a d d i t i o n a l m o l e of a c t i v e m e t h ­
ylene compound
to y i e l d a b i s c o m p o u n d
A consistent mechanism
condensations
as ( 1 ) .
for the w i d e r a n g e of
in a s i n g l e u n i f i e d m e c h a n i s m seems
Knoevenagel
impossible.
T h e r e is e v i d e n c e for the e x i s t e n c e of t w o m e c h a n i s m s
ing on the type of b a s e u s e d .
The intermediacy
Schiff b a s e s w i t h the u s e of p r i m a r y
depend­
of i m i n e s
a m i n e s and a m m o n i a
and
is
3—6
favored.
H o w e v e r , in p o l a r
mechanism
s o l v e n t s t h e H a n n and
Lapworth
is f a v o r e d , w h e r e i n the b a s e r e m o v e s a p r o t o n
the a c t i v e m e t h y l e n e c o m p o u n d .
The resonance
from
stabilized
a n i o n then adds to the c a r b o n y l forming an i n t e r m e d i a t e
droxy 1
compound.7-10
Cope
'
found t h a t a m i n e salts of o r g a n i c a c i d s
the p r e s e n c e of a c e t i c acid w e r e b e t t e r c a t a l y s t s t h a n
bases.
hy­
T h e c o n t i n u o u s r e m o v a l of w a t e r from the
w a s a l s o s h o w n to i n c r e a s e the y i e l d s .
a m o u n t s of acid to b e p r e s e n t d u r i n g
been substantiated.-^
free
condensation
The n e e d for
the c o n d e n s a t i o n
The temperature
in
and c h o i c e of
small
has
catalyst
n e e d e d t o carry o u t the c o n d e n s a t i o n d e p e n d s o n the n a t u r e
the r e a c t a n t s .
The m o s t c o m m o n l y used c a t a l y s t s in the
Knoevenagel
of
3
condensation have been pyridine, piperdine, and ammoniu
amine acetates. Other catalysts employed besides these
amino acides, basic resins, sodium hydroxide, acetic
dride, zinc chloride, titanium tetrachloride and potass
fluoride.
The Michael condensation, unlike the Knoevenagel
densation for carbon-carbon double bond formation, is
cess for alkylation of a carbon-carbon double bond.
densation is the nucleophilic addition of an anion,
resonance stabilized, to a carbon-carbon double bond
a, 3-unsaturated aldehyde, ketone, nitrile, or carbo
acid derivatives. These unsaturated compounds are gene
referred to as Michael acceptors, characterized by t
ence of an electron-withdrawing group capable of stab
a carbanionic intermediate of the reaction. The con
takes place under the influence of basic reagents.15
acrylonitrile is the Michael acceptor, the process
ly known as cyanoethylation.^
The mechanism of the Michael condensation has
established.17-21 general representation of the reaction
is as follows, where L-^, L , L3 represent labilizin
L^—CH2"-1^ ^
A
2
(3)
(4)
(III)
4
L -C!H-CH -CH-L
1
L^, L
2
2
or — C H O
2
2
+ BH
-
or b o t h may be — C O O R ,
—S0 R,
—N0 ,
3
or — S 0 R .
2
and L
3
*
L -CH-CH -CH -L
1
—COR,
2
—CN,
may be — C O O R ,
anism three conclusions
can be r e a c h e d :
+ B
—CONH ,
—COR,
(5)
—N0 ,
2
2
—CN,
—CONH ,
2
(4) is
The carbanionic
(III) is r e s o n a n c e s t a b i l i z e d by L^.
generating
3
T h e r a t e - l i m i t i n g r e a c t i o n step
f o r m a t i o n of a n e w c a r b o n - c a r b o n b o n d .
mediate
2
inter­
F r o m the m e c h ­
1) the b a s e
for
the a n i o n is r e g e n e r a t e d , t h e r e f o r e o n l y a c a t a ­
lytic a m o u n t of b a s e is r e q u i r e d , 2) the M i c h a e l p r o c e s s
r e v e r s i b l e r e q u i r i n g an e x c e s s of a c t i v e m e t h y l e n e
and 3) d u e to the r e v e r s i b i l i t y
banionic
the
intermediate
is
compound,
and s t a b i l i z a t i o n of the c a r ­
(III) side r e a c t i o n s are p o s s i b l e .
s e q u e n t l y , the M i c h a e l c o n d e n s a t i o n
is e f f e c t e d u s i n g
Con­
the
m i l d e s t p o s s i b l e c o n d i t i o n s , w e a k b a s i c c a t a l y s t , low t e m p e r ­
a t u r e , and s h o r t r e a c t i o n t i m e s .
T h e c a t a l y s t s m o s t c o m m o n l y used
in the M i c h a e l
con­
densation have been piperidine, pyridine, triethylamine. p o ­
tassium hydroxide, benzyltrimethylammonium
B),
hydroxide
sodium hydroxide, sodium ethoxide, potassium
s o d i u m h y d r i d e , or o t h e r m e t a l a m i d e s .
(triton
t-butoxide,
Besides these, other
less f r e q u e n t l y used c a t a l y s t s h a v e b e e n a c i d i c
catalysts
such as b o r o n t r i f l u o r i d e , zinc c h l o r i d e , and s u l f u r
as w e l l a s , the b a s i c c a t a l y s t s c a l c i u m h y d r i d e ,
dioxide,
sodium
cyanide, potassium carbonate, sodium triphenylmethide,
and
5
potassium
1
fluoride. -*
P o t a s s i u m F l u o r i d e as a B a s e
T h e use of f l u o r i d e as a b a s i c c a t a l y s t in o r g a n i c r e ­
a c t i o n s is only a r e l a t i v e l y r e c e n t d e v e l o p m e n t .
The
ability
of f l u o r i d e ions to a c t as a b a s e can be r a t i o n a l i z e d .
f l u o r i d e ion is m u c h s m a l l e r than o t h e r h a l i d e i o n s ,
fore, increasing
The result
t h i s e f f e c t m e a n s f l u o r i d e w o u l d h a v e an i n c r e a s e d
fluoride
there­
the c h a r g e to v o l u m e r a t i o , l e a d i n g to a
g r e a t e r e f f e c t at c e n t e r s of p o s i t i v e c h a r g e .
for a p r o t o n .
The
T h i s f a c t is e s t a b l i s h e d
from d a t a
affinity
showing
i o n s , or b o n d e d f l u o r i n e , f o r m i n g s t r o n g e r
b o n d s than o t h e r i o n s . ^ 3 / 2 4
b e e n used as a f l o u r i n a t i n g
Nesmeyanov^
Potassium fluoride has
a g e n t in o r g a n i c
found t h a t u p o n h e a t i n g
hydrogen
mainly
chemistry.^5
trichloroacetic
acid in n i t r o b e n z e n e w i t h dry p o t a s s i u m f l o u r i d e , a g a s
volved
and c h l o r o f o r m formed in 7 0 % y i e l d
pected trifluroacetic
acid.
Other carboxylic acids were
and c y c l o h e x a n o n e , r e s p e c t i v e l y .
c a r b o n y l a t i o n of c h l o r a l w a s a l s o found to o c c u r
ly in r e f l u x i n g , a b s o l u t e e t h a n o l .
yield­
The d e -
showed
of a d i p i c acid
with
f l u o r i d e to b e the r e m o v a l of the acid p r o t o n
f l u o r i d e f o r m i n g the m o n o c a r b o x y l a t e
carboxylates
anion.
also
spontaneous­
Rand, et al.,^?
the i n i t i a l step in the d e c a r b o x y l a t i o n
potassium
e-
i n s t e a d of the e x ­
found to d e c a r b o x y l a t e , w i t h a d i p i c and p i m e l i c a c i d s
ing c y c l o p e n t a n o n e
of
by
This anion d e -
f o r m i n g a c a r b a n i o n w h i c h then c y c l i z e s and
elim-
6
inates
hydroxide.
Rand, et a l . , ^ 8 , 2 9
zene u n d e r g o e s
potassium
]
that N - c h l o r o b e n z a m i d e
rearrangement
phenyl isocyanate
in the p r e s e n c e of
The m e c h a n i s m
fluoride removing
a Hoffmann-type
of the starting
6
5
of p o t a s s i u m
>
by
The
N-chlorobenzamide
the N - b e n z o y l - N * - p h e n y l u r e a
+ KF
con­
giving phenyl isocyanate.
f l u o r i d e , two
in
high
dependent
equivalents
amide to one e q u i v a l e n t of p o t a s s i u m
C H -$-NH
anhydrous
the amide p r o t o n , followed
The y i e l d of the p r o d u c t w a s found to be
upon the c o n c e n t r a t i o n
in b e n ­
for the r e a c t i o n w a s
then adds one m o l e of the
with hydrolysis yielding
yields.
o u n c
a Hofmann reaction
fluoride.
sistent w i t h
f
fluoride.
[ C H - § - N - C l ] ~ + HF
(6)
C H -N=C=0
(7)
6
5
CI
[C H -1!-N-C1] "
6
Aoyama
a base
>
5
3 0 - 3 3
5
+ CI"
has used a n h y d r o u s p o t a s s i u m
in the K n o e v e n a g e l
conditions.
6
condensation
The m o s t commonly
under a variety
used s o l v e n t s w e r e
e t h e r or e t h a n o l and in m a n y c a s e s n o s o l v e n t .
densed ethylcyanoacetate with various aromatic
ethylacetoacetate
with aliphatic ketones.
and
of
Aoyama
con­
aldehydes,
alde­
ethylcyanoacetate
M a l o n i c e s t e r s and a c e t o a c e t i c
to react w i t h the a l i p h a t i c k e t o n e s under these
ditions.
3/
as
diethyl
and d i e t h y l m a l o n a t e w i t h a l i p h a t i c
hydes, acetone with ethylcyanoacetate,
failed
fluoride
ester
con­
H o w e v e r , S a k w e a i * w a s able to c o n d e n s e e t h y l m a -
7
lonate and e t h y l a c e t o a c e t a t e w i t h a l i p h a t i c a l d e h y d e s .
y i e l d s of the r e a c t i o n s ranged
required external
Rand^5/36
catalyst
from 20 to 8 0 % and
usually
heating.
showed p o t a s s i u m
f l u o r i d e to a c t as a b a s i c
in the K n o e v e n a g e l c o n d e n s a t i o n
of b e n z a l d e h y d e
cyclohexanone with malononitrile, ethyl cyanoacetate,
diethyl malonate.
yl cyanoacetate
T h e k i n e t i c s of the c y c l o h e x a n o n e
condensation
photometrically.
in e t h a n o l w a s s t u d i e d
The kinetics
indicated
t i o n , f i r s t o r d e r in the f l u o r i d e .
From kinetic
as the m e t a l f l u o r i d e ion p a i r a b s t r a c t i n g
+ ^CH
active methylene
2
v
compound
:.
H
+
fluoride
ranging
from
and
conduct­
from
CH
found s u c c e s s f u l . 3 7 - 4 2
The
the
(8)
Ethanol
was
temperatures
40°C to r e f l u x i n g e t h a n o l t e m p e r a t u r e .
ranged
the
condensations
some e x t e r n a l h e a t i n g , w i t h
for the c o n d e n s a t i o n s
reac­
postulated
a proton
+
eth­
spectro-
as a c a t a l y s t in
the c o m m o n s o l v e n t or n o s o l v e n t at a l l .
generally required
and
forming a carbanion.
T h e use of p o t a s s i u m
Michael condensation was
MF
or
and
a third-order
a n c e d a t a the first step of the c o n d e n s a t i o n w a s
MF
The
The
time
f r o m o n e h o u r t o , as m u c h a s ,
forty-eight hours giving yields
f r o m 40 t o 8 0 % .
W h e n d o n o r s of the M i c h a e l c o n d e n s a t i o n , such as e t h y l nitroacetate, nitroketones with a C H 2 N O 2
t r o a l k a n e s , are used w i t h p o t a s s i u m
double
g r o u p , and
fluoride
gem-dini-
as the b a s e , a
salt is f o r m e d , for e x a m p l e , g e m - d i n i t r o e t h a n e
formed
8
C^H .INT C> K„F .
2 4 2 4 2 2
The double
c o m p o u n d s w i t h a pKa
salts w e r e
less than
7.
found
to be formed
The d o u b l e
by
Y
salts a l s o
the n o r m a l M i c h a e l p r o d u c t w h e n an a c c e p t o r w a s p r e s e n t ,
cept
gave
ex­
for the n i t r o k e t o n e s w h i c h gave c o n d e n s a t i o n p r o d u c t s
acceptors reacting with nitromethane.
d o u b l e salts s u p p o r t s
tion w i t h p o t a s s i u m
the a s s u m p t i o n
The f o r m a t i o n of
that the M i c h a e l
fluoride p r o c e e d s via
of
such
reac­
f o r m a t i o n of a
carbanion.^3
Potassium
f l u o r i d e has also been used to
aldol c o n d e n s a t i o n s , ^ M i c h a e l - K n o e v e n a g e l
5
q u e n c e s , ' * ' ^ and p o l y f l u o r o a l k y l a t i o n . ^
f l u o r i d e s have a l s o been used
whereby
dehydration
to p r o v i d e a h o m o g e n o u s
in p o l a r , a p r o t i c
the t e t r a a l k y l a m m o n i u m
and h i g h e r t e m p e r a t u r e s
to e t h y l e n e , t r i e t h y l a m i n e
and h y d r o g e n
hexaoxatricyclo
dicyclohexyl-18-crown-6
increased
the a d d i t i o n of
the s o l u b i l i t y
of p o t a s s i u m
This increase
ride also accompanied
(4).
5 3
2,5,8,15,18,21-
for
(ethylene g l y c o l
in the s o l u b i l i t y
structure]
mono-n-butyl
of p o t a s s i u m
an i n c r e a s e in the r e a c t i v i t y
The g r e a t e s t r e a c t i v i t y w a s
termed
f l u o r i d e in a c e t o n i ­
f l u o r i d e as a base in the f o r m a t i o n of a c e t y l e n e
ture
un­
degrading
commonly
[see later d i s c u s s i o n
t r i l e , D M F , and b u t y l c e l l u l o s e
ether).
fluoride.
[20.4.0.0^'Hexacosane,
However,
found to be
stable at room t e m p e r a t u r e
found
system,
elimination
solvents.48-52
f l u o r i d e s h a v e been
N a s o and Ronzini
se­
Tetraalkylammonium
the f l u o r i d e acts as a b a s e , to e x p l o r e
reaction mechanisms
catalyze
found in
of
from
fluo­
the
struc­
acetonitrile
9
P-N0 C H,
2 6 4 ^
o
/
c
Br
C=C
(9)
(IV)
with
and
53 to 7 1 % c o n v e r s i o n
to a c e t y l e n e w i t h the crown
0% c o n v e r s i o n w i t h no crown p r e s e n t .
w a s found to occur
Less of an
in DMF and b u t y l c e l l u l o s e
Pedersen55-61
cyclic polyethers.
of the p o l y e t h e r s
first isolated
charged
to complex
interactions
the alkali m e t a l c a t i o n s
ability
and
Pedersen described
and a t t r i b u t e d
in
many
their f o r m a t i o n
are s y m m e t r i c a l l y
to
negatively
arranged
also gave these m a c r o c y l i c p o l y e t h e r s
trivial nomenclature
are a s s i g n e d
of
"crown" c o m p o u n d s .
on the following b a s i s :
of h y d r o c a r b o n r i n g s , if p r e s e n t ,
in the p o l y e t h e r
4) the number
placements
symmetrical
asym.
the m a c r o -
in
the
ring.
Pedersen
atoms
and d e s c r i b e d
b e t w e e n the c a t i o n and the
o x y g e n atoms w h i c h
polyether
present.^4
The m o s t n o t a b l e d i s c o v e r y w a s the
initial complexes
ion-dipole
great­
Ethers
some cases to form stable c o m p l e x e s .
of these
effect
although
er c o n v e r s i o n s w e r e o b t a i n e d w h e n the c r o w n w a s
Crown
present
ring,
the
The t r i v i a l
1) the number
and
2) the total number
3) the c l a s s n a m e , c r o w n ,
of o x y g e n atoms in the p o l y e t h e r
ring.
names
kind
of
and
The
of the h y d r o c a r b o n r i n g s and o x y g e n atoms are
as p o s s i b l e , and the e x c e p t i o n s
For e x a m p l e ,
structure
are i n d i c a t e d
(V) has the s y s t m a t i c name
as
by
2,5,
10
8 ,15 ,18 , 2 1 - h e x a o x a t r i c y c l o | 20 . 4 . 0 . 0^ ' ^] hoxacosano or d i cyclohexyl-18-crown-6
r e f e r r e d t o p r e v i o u s l y by t r i v i a l
V
nomenclature.
VI
Structure
(VI) has t h e s y s t e m a t i c name 1 , 4 , 7 ,
1 0 , 1 3 , 1 6 - h e x a o x a c y c l o o c t a d e c a n e or 18-crown-6 by t h e
nomenclature.
Structure
trivial
(VI) w i l l be r e f e r r e d t o as 18-crown-
6 t h r o u g h o u t t h e remainder of t h e t h e s i s .
New and improved s y n t h e s i s have r e c e n t l y been p u b l i s h e d
for v a r i o u s crown e t h e r s y s t e m s , ^ ' ^ i n c l u d i n g 18-crown-6^^
12-crown-4,
and 15-crown-5.
Besides t h e oxygenated crown
e t h e r s , crown e t h e r s c o n t a i n i n g o t h e r h e t e r o - a t o m s have been
fi fi — 7 1
synthesized for i n v e s t i g a t i o n .
Crown e t h e r s have a l s o
been p r e p a r e d i n polymeric form w i t h m o l e c u l a r w e i g h t s r a n g ­
ing from 30,000 t o 100,000 by r a d i c a l or a n i o n i c
initiation
reactions.72-75
The a b i l i t y of t h e crown e t h e r s t o complex a l k a l i
m e t a l c a t i o n s has d i r e c t e d much e f f o r t t o e x p l o r i n g t h e s e
interactions.
With t h e formation and i s o l a t i o n of s o l i d com­
p l e x e s , x - r a y c r y s t a l l o g r a p h y was used t o e l u c i d a t e
structures.
7 6 - 8 8
these
The s o l u t i o n chemistry of crown e t h e r s
11
i n t e r a c t i n g w i t h m e t a l c a t i o n s has been studied by
etry,
89—91
potentiometry,
92
distribution
equilibria,
94-96
ble and u l t r a v i o l e t
spectroscopy,
colorim93
visi-
97
ESR,
and p a p e r
chro-
98
matography.
Other complexes
of crown e t h e r s b e s i d e s
99-101
m e t a l c a t i o n c o m p l e x e s h a v e a l s o been
the
reported.
C r o w n e t h e r s have b e e n used as addends to
investigate
the i o n - p a i r p r o c e s s e s of f l u o r e n y l
salts in s o l u t i o n .
crown e t h e r s w e r e
ion-pair dissociation
found
to i n c r e a s e
The
in
a v a r i e t y of s o l v e n t s by c o n v e r t i n g c o n t a c t i o n - p a i r s to
s o l v e n t - s e p a r a t e d ion p a i r s . 1 0 2 - 1 1 4
B e c a u s e of this e f f e c t ,
crown e t h e r s h a v e a l s o b e e n used as a d d e n d s in e l i m i n a t i o n
reactions
as a d e f i n i t i v e m e a n s of d e t e r m i n i n g
base association
in these
Few synthetic
the e f f e c t
of
reactions.H5-119
applications
of the crown e t h e r s
have
120
been reported.
manganate
Sam and Simmons
solubilized
in b e n z e n e w i t h c o n c e n t r a t i o n s
Molar using dicyclohexyl-18-crown-6.
found c a p a b l e of o x i d i z i n g o r g a n i c
potassium
as high as
0.03
Such a s o l u t i o n
substrates
per­
was
as o l e f i n s , a l ­
c o h o l s , a l d e h y d e s , and a l k y l b e n z e n e s u n d e r mild
conditions
in
121
excellent yields.
18-crown-6
Sam and Simmons
dicyclohexyl-
to s o l u b i l i z e p o t a s s i u m b r o m i d e and i o d i d e in a c e ­
tone to carry out n u c l e o p h i l i c
late.
also used
substitutions
on n - b u t y l
P o t a s s i u m m e t h o x i d e w a s shown a l s o to i n c r e a s e
activity when dicyclohexyl-18-crown-6
was present.
brosy-
in r e ­
Liotta
122
and H a r r i s
in b e n z e n e and
solubilized
potassium
acetonitrile.
This
fluoride with
"naked"
18-crown-6
fluoride
showed
12
marked
activity
to act as a n u c l e o p h i l e
123
conditions.
potassium
Liotta
cyanide
in the p r e s e n c e of
and base under
124
'
a l s o found p o t a s s i u m a c e t a t e
to have increased
reactivity
in
18-crown-6.
thesis w a s to i n v e s t i g a t e
the ability of
"naked"
and b e n z e n e ,
consisted
n a g e l , and a l k y l a t i o n
of 18-crown-6
of r u n n i n g s e l e c t e d M i c h a e l ,
reaction
in the p r e s e n c e and
times and p r o d u c t s
The f o r m a t i o n of three n o v e l n o n - m e t a l l i c
is
discussed.
this
solvents,
in the p r e s e n c e of 1 8 - c r o w n - 6 .
reactions
comparing
in
fluoride
ions to act as a b a s e in polar and n o n p o l a r a p r o t i c
investigation
and
acetonitrile
T h e r e f o r e , the p u r p o s e of the w o r k p r e s e n t e d
acetonitrile
mild
18-crown-6
The
Knoeve­
absence
isolated.
complexes
13
CHAPTER
II
EXPERIMENTAL
A l l b o i l i n g p o i n t s and m e l t i n g p o i n t s reported
thesis are u n c o r r e c t e d
and recorded
Infrared
spectrum w e r e obtained
infrared
spectrophotometer
in d e g r e e s
films
237B
NMR d a t a w e r e
on a V a r i a n A 6 0 D or a V a r i a n T60 s p e c t r o m e t e r .
w e r e obtained
E l m e r RMV-7L
Foundation]
absorp­
spectra
Perkin-
[bought by funds p r o v i d e d by N a t i o n a l
Science
G l p c w o r k w a s carried out on a
V a r i a n M o d e l 90P G a s C h r o m a t o g r a p h w i t h t h e r m a l
detector
CCl^)
obtained
Mass
on e i t h e r a V a r i a n M 6 6 or a H i t a c h i
spectrometers.
grating
(neat or
or as p o t a s s i u m b r o m i d e p e l l e t s using the 1 6 0 1 . 4 cm~^
tion of p o l y s t y r e n e as a r e f e r e n c e .
this
centigrade.
on a P e r k i n - E l m e r
as thin liquid
in
and h e l i u m as c a r r i e r g a s .
was p e r f o r m e d by A t l a n t i c M i c r o l a b ,
Elemental
conductivity
microanalysis
Inc., A t l a n t a ,
Georgia.
Chemicals
Acetonitrile
(Fisher and A l d r i c h ) w a s used
further purification.
sodium
(2-5 g. per
tion 8 0 . 1 - 8 1 ° C .
Benzene
without
(Fisher) w a s d i s t i l l e d
liter) u n d e r n i t r o g e n collecting
Acrylonitrile
from
the
(Fisher) w a s p u r i f i e d by
frac­
the
125
method
without
of F i e s e r
and stored
further p u r i f i c a t i o n .
in a b r o w n b o t t l e and
Ethyl acrylate
d i s t i l l e d u n d e r reduced p r e s s u r e
(< 1 mm)
used
(Eastman)
and c o l l e c t e d
was
in a
14
round b o t t o m
stored
flask, immersed
in a dry i c e / a c e t o n e b a t h
in a b r o w n b o t t l e in the r e f r i g e r a t o r .
(Fisher) w a s d i s t i l l e d w i t h the c o l o r l e s s
b.p.
178-180°C
stored
(740 m m )
[lit.
in a b r o w n b o t t l e in r e f r i g e r a t o r .
(Eastman) w a s used w i t h o u t
Malonate
1 2 7
Ethyl
(Fisher) w a s d i s t i l l e d , b . p . 6 3 - 6 7 ° C
b.p. 223-224°C
[lit.
(760 mm)]
1 2 7
and
Cyanoacetate
Diethyl
Potassium
was dried
fluoride
and stored
(0.1 m m )
in a b r o w n
Diethyl ether
bottle
further
(Fisher) for e x ­
purification.
(ROC/RIC) used in these
in an o v e n at 120°C for 12 h o u r s .
f l u o r i d e w a s then finely p o w d e r e d
feree! to a h o t 500 m l . b e a k e r .
The
reactions
potassium
in a h o t m o r t a r and
The potassium
trans­
fluoride
to dry for 12 a d d i t i o n a l h o u r s b e f o r e u s a g e .
powdered potassium
Ma­
the m a t e r i a l s o l i d i f i e d , m . p .
m . p . 31.7°C"J.
t r a c t i o n s w a s used w i t h o u t
allowed
(760 mm)]
further p u r i f i c a t i o n .
in the r e f r i g e r a t o r , w h e r e b y
31°C
collected,
(Fisher) w a s used w i t h o u t f u r t h e r p u r i f i c a t i o n .
lononitrile
[lit.
Benzaldehyde
fraction
b . p . 179.1
and
was
The
f l u o r i d e w a s then s t o r e d in the o v e n
at
120°C at a l l t i m e s .
1,4,7,10,13,16-Hexaoxacyclooctadecane
(18-crown-6)
1 8 - c r o w n - 6 w a s p r e p a r e d by the m e t h o d of C r a m ,
Liotta,
64
et a l .
A f i v e - l i t e r , three n e c k e d
flask e q u i p p e d w i t h
m e c h a n i c a l s t i r r e r and w a t e r - c o o l e d b e a r i n g , a r e f l u x
con­
d e n s e r , and a 500 m l . d r o p p i n g f u n n e l , w a s c h a r g e d w i t h
of t r i e t h y l e n e g l y c o l
( M a t h e s o n , C o l e m a n and B e l l 1.5
a
230
moles)
g.
15
in 1000 m l . THF
(Fisher).
Potassium hydroxide
85% pellets) was dissolved
added
in w a t e r
(218 g.
Fisher,
(120 m l . d i s t i l l e d )
and
in one p o r t i o n to the stirred t r i e t h y l e n e g l y c o l m i x ­
ture.
After
30 m i n u t e s of s t i r r i n g at a m b i e n t
temperature
(solution slowly d a r k e n s ) , a s o l u t i o n of 280 g. of
dichloro-3,6-dioxaoctane
(Eastman p r a t i c a l , 1.5 m o l e s )
m l . THF w a s added in a thin s t r e a m to the stirred
mixture.
n o t e d to b e d i s c o l o r e d
orator.
A f t e r this t i m e , the s o l u t i o n
200
heated
was
and solid p o t a s s i u m c h l o r i d e w a s
T h e bulk of the s o l v e n t w a s r e m o v e d on a r o t a r y
pre­
evap­
T h e r e s i d u a l o i l and solid w a s t h e n s t i r r e d w i t h a
mechanical
s t i r r e r w i t h a liter of m e t h y l e n e c h l o r i d e ,
t e r e d , and d r i e d over M g S O ^ .
concentrated
vacuum.
in
reaction
W i t h the a d d i t i o n c o m p l e t e d , the m i x t u r e w a s
to r e f l u x for 15 h o u r s .
sent.
1,8-
This solution was filtered
on a rotary e v a p o r a t o r and d i s t i l l e d u n d e r
A f t e r an i n i t i a l f o r e r u n b o i l i n g
crude crown ether
(0.2 m m ) .
fil­
(140 g.,
128-150°C
t h r o u g h the a c e t o n i ­
T h e c r u d e c r o w n w a s p l a c e d in a 250 m l . E r l e n ­
m e y e r flask and 200 m l . of a c e t o n i t r i l e w a s a d d e d .
s u l t i n g s l u r r y w a s h e a t e d u n t i l all the m a t e r i a l
The re­
dissolved.
T h e n a m a g n e t i c s t i r r i n g b a r w a s added and the s o l u t i o n
stirred vigorously.
flask's top.
A drying tube
was
(Drierite) w a s p u t on
A s the s o l u t i o n c o o l e d to r o o m
the
temperature,
f i n e , w h i t e c r y s t a l s of the c r o w n e t h e r / a c e t o n i t r i l e
were formed.
a
(0.2 m m ) ,
35%) w a s c o l l e c t e d , b . p .
This material was purified
trile c o m p l e x .
25-127°C
and
T h e flask w a s f u r t h e r cooled in an
complex
ice/acetone
16
bath
to e f f e c t complete p r e c i p i t a t i o n .
n i t r i l e c o m p l e x was filtered
bottom
flask.
A magnetic
T h e crown
and t r a n s f e r e d
to a 240 m l . round
stirring b a r w a s added to the
which was also equipped with a vacuum take-off
mantle.
The p u r e crown e t h e r
ing and w a s sealed
pure 1 8 - c r o w n - 6
(66 g.,
ether m e l t e d
and ir a b s o r p t i o n s
(alkane C - H ) , and
1120 c m
- 1
Michael
Acrylonitrile
in the NMR
6 3
m l . round b o t t o m
6.25
g.
was
flask,
2.65 g.
s o l u t i o n w a s added
1.30 g.
and allowed
weighed
and
and
diluted
Into a
(0.05 m o l e s , 2.0
M)
diluted
(Fisher).
The
to a three necked
flask e q u i p p e d w i t h a m a g n e t i c
of 1 8 - c r o w n - 6 w a s added
1350
(0.055 m o l e s ,
(Fisher).
(Fisher) w a s d i r e c t l y w e i g h e d
solution,
TMS)
4
Condensation
flask,
g r o u n d g l a s s s t o p p e r , r u b b e r septum,
ethylcyanoacetate
39-40°],
Condensations
to the m a r k w i t h a d d i t i o n of a c e t o n i t r i l e
ethylcyanoacetate
m.p.
( C C 1 , internal
ethylcyanoacetate directly
of a c r y l o n i t r i l e
The
(alkane C - H ) , 1450 and
and E t h y l c y a n o a c e t a t e
25-ml. volumetric
on c o o l ­
2
to the m a r k w i t h a d d i t i o n of a c e t o n i t r i l e
second
(Ca.
flask u n d e r N »
[lit.
to
(ether C - O ) .
Into a 25-ml. volumetric
2.2 M ) of
(0.3
slight w a r m i n g
at 36-38°C
(neat) at 2875
flask
heating
45%) s o l i d i f i e d
in the round b o t t o m
showed only a s i n g l e t at 6 3.5
I.
and
T h e a c e t o n i t r i l e w a s removed u n d e r a v a c u u m
0.1 mm) o v e r a p e r i o d of six h o u r s w i t h
40°).
ether/aceto-
100-
stirring
and t h e r m o m e t e r .
To
bar,
the
(0.0049 m o l e s , 0.098 M)
to stir for five m i n u t e s .
17
Then
3.2 g.
added
(0.055 m o l e s ) of hot, dry p o t a s s i u m
to the o t h y c y a n o a c e t a t e
for five m i n u t e s .
solution and allowed
The a c r y l o n i t r i l e
to
was
stir
s o l u t i o n w a s slowly
ed by s y r i n g e over a f i v e - m i n u t e period
slowly heated
fluoride
and the
to 45°C d u r i n g this t i m e .
add­
reaction
The s o l u t i o n
was
o
cooled
in an i c e - w a t e r bath to a t e m p e r a t u r e
moved.
After
ten m i n u t e s of r e a c t i o n
reaction mixture was withdrawn
resonance
corresponding
NMR s p e c t r u m .
and its NMR r u n .
The r e a c t i o n m i x t u r e w a s stirred
solution during
found
this t i m e .
mixture was poured
300 m l . of d i e t h y l e t h e r .
The organic
dried over M g S O ^ ,
m a t e r i a l w a s removed
amounted
m.p.
36-37°C
g
(KBr) at 2250 cm""
NMR p e a k s
(86%) of
[lit.
1
The
The
extracted
layer
and
filtered
This
Only a low b o i l i n g
and the m a t e r i a l
The solid m a t e r i a l after s u b l i m a t i o n
to 9.4
1 2 8
'
1 2 9
the
the
and shown to be e t h y l c y a n o a c e t a t e
The pot m a t e r i a l w a s r e m o v e d
solidified.
in
reaction
and e t h e r removed by rotary e v a p o r a t o r .
left an o i l w h i c h could not be d i s t i l l e d .
the
hours
funnel.
and the aqueous p h a s e
re­
proton
and s t i r r e d .
into a s e p a r a t o r y
ether e x t r a c t s w e r e combined,
2 g.).
four
four h o u r s , the
into 250 m l . of w a t e r
layer w a s s e p a r a t e d
under v a c u u m ,
Vinyl
in the N M R s p e c t r u m of
After
a q u e o u s m i x t u r e was p o u r e d
twice w i t h
t i m e , a sample of
to a c r y l o n i t r i l e w a s not found
and no v i n y l p r o t o n s w e r e
organic
of 30 C and
(^
slowly
in v a c u o
y-carbethoxy-y-cyanopimelonitrile:
m . p . 38°C]; infrared
(nitrile -C=N) and
(CDCl^, i n t e r n a l TMS)
1740 c m "
at 6 4.40
absorption
1
(ester C=0) ;
(2H q u a r t e t .
18
—CH -Me),
at 6 2.8-1.8
2
1.36
(311 t r i p l e t , C H ^ - ) ;
ments
was
(8H m u l t i p l e t , N C - C H - C H - ) ,
2
and at 6
2
and m a s s s p e c t r u m m / e a b u n d a n t
1 7 4 , 1 0 7 , 6 8 , 5 4 , 4 1 , and
27.
No polymeric
frag­
material
found.
S i m i l a r l y , the same r e a c t i o n w a s r u n in the a b s e n c e
18-crown-6.
D u r i n g the i n i t i a l four h o u r s of the
N M R ' s of the r e a c t i o n m i x t u r e
a m o u n t of a c r y l o n i t r i l e
reaction,
showed a steady d e c l i n e in
in the m i x t u r e .
The mixture
the
was
stirred
four a d d i t i o n a l h o u r s .
8.8
(80%) of y - c a r b e t h o x y - y - c y a n o p i m e l o n i t r i l e w a s
g.
of
A f t e r the w o r k u p , as a b o v e ,
col­
lected.
II.
Into a 2 5 - m l . v o l u m e t r i c
f l a s k , 6.25
g.
(0.055 m o l e s ,
2.2 M ) of e t h y l c y a n o a c e t a t e w a s d i r e c t l y w e i g h e d
to the m a r k w i t h a d d i t i o n of a c e t o n i t r i l e .
25-ml. volumetric
f l a s k , 5.30 g.
lonitrile was directly weighed
acetonitrile.
three necked
and
Into a
diluted
second
(0.1 m o l e s , 4.0 M) of
and d i l u t e d
The e t h y c y a n o a c e t a t e
to the m a r k
acry­
with
s o l u t i o n w a s a d d e d to a
1 0 0 - m l . round b o t t o m flask e q u i p p e d w i t h a m a g ­
netic stirring b a r , ground glass stopper, rupper septum,
thermometer.
moles,
T o the e t h y l c y a n o a c e t a t e
solution
1.30
0.098 M ) of 1 8 - c r o w n - 6 w a s added and a l l o w e d
for five m i n u t e s .
Then
3.2 g.
g.
to
and
(0.0049
stir
(0.055 m o l e s ) of h o t , dry p o ­
t a s s i u m f l u o r i d e w a s added to the e t h y l c y a n o a c e t a t e
and a l ­
lowed
solution
to
stir for five m i n u t e s .
The acrylonitrile
w a s s l o w l y added by s y r i n g e over a s e v e n - m i n u t e p e r i o d
and
the r e a c t i o n
The
slowly h e a t e d
to 45° C d u r i n g this t i m e .
19
flask w a s immersed
in an i c e - w a t e r b a t h , cooled
ture of 30° C and r e m o v e d .
The t e m p e r a t u r e
again but then slowly d r o p p e d
to a
rose to 35° C
to 25° C after one half
The s o l u t i o n w a s also a slight y e l l o w in c o l o r .
m i n u t e s of r e a c t i o n
tempera­
hour.
After
t i m e , a sample of the r e a c t i o n
mixture
was withdrawn
and its N M R w a s t a k e n .
corresponding
to a c y l o n i t r i l e w a s not found in the N M R
trum.
Vinyl proton
The r e a c t i o n m i x t u r e w a s stirred
vinyl proton resonance was
solution during
this t i m e .
funnel.
arated
and the a q u e o u s p h a s e e x t r a c t e d
The o r g a n i c
The o r g a n i c
removed by rotary e v a p o r a t o r ,
left in the round b o t t o m
and
a vacuum take-off.
light, b r o w n w a x y
solid.
m.p.
36-37° C
[lit.
Similarly,
18-crown-6.
1 2 8
ether
rotare­
gave a
The solid after s u b l i m a t i o n
in
vacuo
y-carbethoxy-y-cyanopimelonitrile;
m.p. 38°, m.p. 37°
C
1
2
9
].
the same r e a c t i o n w a s run in the a b s e n c e
The d e c r e a s e
in a c r y l o n i t r i l e w a s
followed
in the m i x t u r e .
The m i x t u r e w a s stirred
of
by
N M R over a 40-hour p e r i o d w i t h a slow but steady d e c l i n e
acrylonitrile
oil
Complete
in v a c u o at ice b a t h t e m p e r a t u r e s
(83%) of
com­
The
for
m o v a l of s o l v e n t s
g.
sep­
300 m l . of
leaving a v i s c o u s o i l .
flask w h i c h w a s used
and e q u i p p e d w i t h
to 9.2
was
layer and ether e x t r a c t w e r e
b i n e d , dried over M g S O ^ , filtered u n d e r a vacuum,
amounted
poured
layer w a s
twice w i t h
no
the
The a q u e o u s m i x t u r e
into a s e p a r a t o r y
vaporation
spec­
for one h o u r and
The r e a c t i o n m i x t u r e w a s
poured
was
resonance
found in the N M R s p e c t r u m of
into 100 m l . of w a t e r and s t i r r e d .
diethyl ether.
ten
in
for
an
20
additional
three h o u r s .
After
the w o r k u p , as a b o v e , 9.6
(84%) of y - c a r b e t h o x y - y - c y a n o p i m e l o n i t r i l e
was
g.
(m.p. 35-36° C)
collected.
III.
moles,
Into a 2 5 - m l . v o l u m e t r i c
flask,
6.25
g.
(0.055
2.2 M) e t h y l c y a n o a c e t a t e w a s d i r e c t l y w e i g h e d
luted to the m a r k w i t h the a d d i t i o n of a c e t o n i t r i l e
over P 2 ^ 5
u n <
volumetric
^
e r
N
2
^
flask,
directly weighed
under N
by a c a n u l l a .
2
5.30 g.
under N
round b o t t o m
flask e q u i p p e d w i t h
Into a second
by a c a n u l l a .
A three n e c k e d
potassium
tum and
The
2
and
3.2 g.
flask u n d e r N
The a c r y l o n i t r i l e
to 40° C and the
bath u n t i l the t e m p e r a t u r e
solution was
removed
and p r o c e d u r e
lized b e l o w
35° C.
and its NMR
and
slowly
in an
The flask
spectrum taken.
icewas
stabi­
time, a
Vinyl pro­
to a c r y l o n i t r i l e w a s not
The r e a c t i o n m i x t u r e w a s stirred
was
temperature
followed u n t i l the t e m p e r a t u r e
corresponding
100 m l . of w a t e r .
The
A f t e r ten m i n u t e s of r e a c t i o n
sample w a s w i t h d r a w n
ton r e s o n a n c e
to 30° C.
sep­
solution
flask w a s immersed
dropped
dry
by c a n u l l a
2
of
(0.0049
(0.055 m o l e s ) h o t ,
added by s y r i n g e over a t e n - m i n u t e p e r i o d .
rose q u i c k l y
1.30 g.
The e t h y l c y a n o a c e t a t e
to the round b o t t o m
five m i n u t e s .
was
glass
flask w a s sealed w i t h a r u b b e r
flushed w i t h N «
transferred
stirred
18-crown-6
fluoride.
25-ml.
100-ml.
a s t i r r i n g b a r , ground
s t o p p e r , and rubber septum w a s charged w i t h
0.098 M)
(dried
to the mark w i t h the a d d i t i o n
acetonitrile
moles,
di­
(0.1 m o l e s , 4.0 M) a c r y l o n i t r i l e
and d i l u t e d
2
and
present.
four h o u r s and then added
The a q u e o u s m i x t u r e w a s p o u r e d
to
into a s e p -
21
aratory
funnel.
phase e x t r a c t e d
organic
MgSO^,
The o r g a n i c
twice w i t h
layer w a s s e p a r a t e d
300 m l .
tary e v a p o r a t o r
amounted
to 10 g.
The
dried
The oil solidified
The solid
(90%) of
aqueous
over
and the ether removed by
to give an o i l .
ing in the r e f r i g e r a t o r .
the
of d i e t h y l e t h e r .
layer and ether e x t r a c t s w e r e c o m b i n e d ,
filtered under a v a c u u m ,
and
ro­
upon
after s u b l i m a t i o n
cool­
in
vacuo
y-carbethoxy-y-cyanopimelonitrile
(m.p. 36° C ) .
Acrylonitrile
I.
and D i e t h y l m a l o n a t e
Into a 2 5 - m l . v o l u m e t r i c
Condensations
flask, 8.80 g.
(0.055 m o l e s ,
2.2 M) of d i e t h y l m a l o n a t e w a s d i r e c t l y w e i g h e d
and
to the m a r k w i t h the a d d i t i o n of a c e t o n i t r i l e .
Into a second
25-ml. volumetric
flask,
5.30 g.
lonitrile was directly weighed
acetonitrile.
three necked
moles,
(0.1 m o l e s , 4.0 M) of
and d i l u t e d
with
The d i e t h y l m a l o n a t e s o l u t i o n w a s added
to a
1 0 0 - m l . round b o t t o m
flask e q u i p p e d w i t h a m a g ­
stopper, rubber
T o the d i e t h y l m a l o n a t e
solution
0.098 M) of 18-crown-6 w a s added
for five m i n u t e s .
The 3.20 g.
septum
g.
(0.0049
and allowed
to
stir
(0.055 m o l e s ) of d r y , hot
f l u o r i d e w a s added to the d i e t h y l m a l o n a t e
to stir
for five m i n u t e s .
The a c r y l o n i t r i l e
added by s y r i n g e over a f i v e - m i n u t e period
action
slowly h e a t e d
of
to 41° C d u r i n g this t i m e .
in an i c e - w a t e r b a t h , cooled to a
30° C, and r e m o v e d .
The t e m p e r a t u r e
and
solution
slowly
immersed
and
1.30
tassium
was
acry­
to the m a r k
n e t i c s t i r r i n g b a r , ground g l a s s
thermometer.
diluted
po­
allowed
was
and the r e ­
The
flask
temperature
increased
again
to
22
38° C but slowly dropped over two hours to 25°
minutes of reaction time a sample of the mixture
and its NMR was taken. Vinyl proton resonance co
to acrylonitrile was found. The decrease in the
was followed by NMR over a three and one-half ho
which time no vinyl proton resonance was found.
was allowed to stir overnight an additional nine a
hours. The reaction mixture was poured into 100-ml
and stirred. The aqueous mixture was poured into
funnel. The organic layer was separated and the
was extracted twice with 300 ml. of diethyl ether
ganic layer and ether extracts were combined, dried
filtered under a vacuum, and the ether removed on
evaporator. This left an oily material which solidi
solid after sublimation in vacuo amounted to 10.8
130 131
of y, y-dicarbethoxypimelonitrile; m.p. 56-57° C [lit
m.p. 61° C;] infrared absorption (KBr) at 2250 cm
CSN) and 1730 cm" (ester C=0) ; NMR peaks (cf
at 6 4.05 (4H quartet, -CH-Me), at 6 2.2-1.8
NC-CH
-CH
-) and at 6 0.96 (6H triplet, CH~); an
trum, m/e abundant, fragments 221, 173, 154, 108,
Similarly, the same reaction was run in the
18-crown-6. The decrease in acrylonitrile was followed
NMR over a 121 hour period with a slow decrease
trile in the mixture. After passage of the 121
action time, the reaction mixture was poured into
1
2
2
2
2
23
w a t e r and s t i r r e d .
aratory
The a q u e o u s m i x t u r e w a s p o u r e d
f u n n e l and the o r g a n i c
layer s e p a r a t e d .
ing a q u e o u s p h a s e w a s e x t r a c t e d
ether.
The organic
into a sep-
The
remain­
twice w i t h 300 m l . of
layer and e t h e r e x t r a c t s w e r e
diethyl
combined,
dried over M g S O ^ , filtered u n d e r a v a c u u m , and the e t h e r r e ­
m o v e d by r o t a r y e v a p o r a t o r .
n o t s o l i d i f y on cooling
tillation yielded
in the f r e e z e r .
5.9 g.
m a l o n a t e and 2.1 g.
T h e r e r e m a i n e d an o i l w h i c h
(0.037) b . p . 40° C
1 3 2
b.p. 175-18-
frared a b s o r p t i o n ,
1735 c m "
4.23
1
(25 m m ) , b . p .
b . p . 96-100
1 3 3
( C C 1 ) at 2240 c m
- 1
(ester C = 0 ) ; N M R p e a k s
(0.1 m m )
(0.6 m m ) ] ; i n ­
(nitrile -C=N)
and
(III, T r i p l e t - C - H )
(4H, m u l t i p l e t C N - C H - C H - ) , and at <S 1.27
3
malonate)
3
2
let, C H ~ ) ;
diethyl
( C D C 1 , i n t e r n a l TMS) at 6
(4H q u a r t e t , - C H ~ M e ) , at 6 3.46
2.7-2.4
104-110
4
dis­
(0.1 m m ) of
( 5 4 % , b a s e d on r e c o v e r e d d i e t h y l
ethyl a-carbethoxy-y-cyanobutyrate;
[lit.
The oil after
did
2
2
and m a s s s p e c t r u m m / e 213
at 6
(6H, t r i p ­
+
( M ) and a b u n d a n t
frag­
m e n t s 1 6 8 , 1 3 3 , 1 1 5 , 1 0 1 , 9 6 , 8 8 , 5 4 , 4 3 , and 2 9 .
II.
Into a 2 5 - m l . V o l u m e t r i c
flask
8.81 g.
(0.055 m o l e s ,
2.2 M ) of d i e t h y l m a l o n a t e w a s d i r e c t l y w e i g h e d
to the m a r k w i t h the a d d i t i o n of a c e t r o n i t r i l e .
25-ml. volumetric
flask
2.65 g.
lonitrile was directly weighed
acetronitrile.
three necked
diluted
Into a second
(0.05 m o l e s , 2.0 M) of
and d i l u t e d to the m a r k
acry­
with
The d i e t h y l m a l o n a t e s o l u t i o n w a s added to a
100-ml. round-bottom
netic stirring b a r , ground-glass
thermometer.
and
flask e q u i p p e d w i t h a m a g ­
stopper, rubber septum,
T o the d i e t h y l m a l o n a t e s o l u t i o n 1.30 g.
and
(0.0049
24
moles,
0.098 M) of
for five m i n u t e s .
tassium
18-crown-6 w a s added and allowed
Then
3.20 g.
f l u o r i d e w a s added
and allowed
to
stir
(0.055 m o l e s ) of dry, hot
to the d i e t h y l m a l o n a t e
to stir five m i n u t e s .
po­
solution
The a c r y l o n i t r i l e
solution
w a s slowly added by syringe over a t h i r t y - f i v e - m i n u t e
period
to a l l o w the s o l u t i o n to heat slowly not e x c e e d i n g
40° C.
The
r e a c t i o n m i x t u r e w a s stirred u n t i l the t e m p e r a t u r e
dropped
to
25° C and remained
stable.
This required
The r e a c t i o n m i x t u r e w a s then poured
stirred.
extracted
twice w i t h
layer r e m o v e d .
This
[lit.
Y,
1 3 0 , 1 3 1
(0.022 m o l e s ) , b . p . 40° C
The pot m a t e r i a l w a s r e m o v e d
solid­
distil­
(0.1 m m ) , of
and
solidified.
in v a c u o y i e l d e d
Y-dicarbethoxypimelonitrile;
5.18
g.
m . p . 54-56° C
m . p . 61° C ] .
Ethyl Acrylate
I.
MgSO^,
The m a t e r i a l after
The solid m a t e r i a l after s u b l i m a t i o n
(73%) of
dried over
organic
left a light y e l l o w o i l w h i c h did not
3.5 g.
diethyl malonate.
The
was
and the ether r e m o v e d on a rotary
ify after three days in a f r e e z e r .
lation y i e l d e d
and
separatory
The a q u e o u s p h a s e
layer and ether e x t r a c t s w e r e c o m b i n e d ,
evaporator.
into a
300 m l . of d i e t h y l e t h e r .
filtered u n d e r a v a c u u m ,
period.
i n t o 1 0 0 - m l . of w a t e r
The a q u e o u s m i x t u r e w a s p o u r e d
funnel and the o r g a n i c
a four-hour
and E t h y l C y a n o a c e t a t e
Into a 2 5 - m l . v o l u m e t r i c
Condensation
flask 6.22
g.
(0.055 m o l e s ,
2.2 M) e t h y l c y a n o a c e t a t e w a s d i r e c t l y w e i g h e d
the m a r k w i t h the a d d i t i o n of a c e t o n i t r i l e .
25-ml. volumetric
flask
10.0 g.
and d i l u t e d
to
Into a second
(0.1 m o l e s , 4.0 M) e t h y l
aery-
25
late w a s d i r e c t l y w e i g h e d
trile.
necked
and d i l u t e d
The ethyl c y a n o a c e t a t e
1 0 0 - m l . round b o t t o m
to the m a r k w i t h
s o l u t i o n w a s added
to a
moles,
T o the e h t y l c y a n o a c e t a t e
Then
f l u o r i d e w a s added
lowed
2.90 g.
to the e t h y l c y a n o a c e t a t e
The flask w a s immersed
rapidly
slowly but s t a b i l i z e d b e l o w
C over the next h o u r .
M
SE 3 0 , 5' x 1 / 4 ,
decreased
(0.0049
to
stir
potassium
s o l u t i o n and a l ­
The e t h y l a c r y l a t e
solution
The t e m p e r a t u r e
tem­
26°
of the
reac­
The a q u e o u s p h a s e w a s e x t r a c t e d
twice w i t h
layer
300 m l . of
layer and ether e x t r a c t s w e r e
filtered under a v a c u u m ,
on a rotary e v a p o r a t o r
in v a c u o y i e l d e d
After
poured
The a q u e o u s m i x t u r e
f u n n e l and the o r g a n i c
11.8 g.
was
separated.
diethyl
combined,
and the e t h e r
to give an o i l .
(3%
acrylate
t i m e , the r e a c t i o n m i x t u r e w a s
into a separatory
distillation
to
over the next twelve h o u r s .
i n t o 1 0 0 - m l . of w a t e r and s t i r r e d .
d r i e d over M g S O ^ ,
to a
increased
of e t h y l
the first ten m i n u t e s
constant
The o r g a n i c
time.
40° C and slowly d r o p p e d
58° C) for d i s a p p e a r a n c e
12.8 h o u r s of r e a c t i o n
this
The
The r e a c t i o n w a s m o n i t o r e d by glpc
rapidly d u r i n g
tion and r e m a i n e d
to 40° C d u r i n g
in an i c e - w a t e r b a t h , cooled
p e r a t u r e of 30° C, and r e m o v e d .
moved
g.
ther­
added by s y r i n g e over a f i v e - m i n u t e p e r i o d .
r e a c t i o n m i x t u r e heated
ether.
1.30
(0.05 m o l e s ) of d r y , hot
to stir for five m i n u t e s .
w a s slowly
poured
solution
and
0.098 M) of 18-crown-6 w a s added and a l l o w e d
five m i n u t e s .
three
flask e q u i p p e d w i t h a m a g n e t i c
s t i r r i n g b a r , ground glass s t o p p e r , r u b b e r septum,
mometer.
acetoni­
The oil
(75%) of d i e t h y l
re­
after
y-
26
carbethoxy-y-cyanopimelate;
228°
(20 m m ) ] ; infrared
C=0) ; N M R p e a k s
(CDC1
-CH - M e ) , at 6 2.7-1.9
2
at 6 1.30
b . p . 156
absorption
(0.15 m m )
(CC1 )
[lit.
1740 c m "
4
, i n t e r n a l T M S ) at 6 4.21
(6 H , q u a r t e t ,
2
^
(9 H, t r i p l e t , - C H ^ ) ; m a s s s p e c t r u m , m / e
and 2 8 ; C
1 3
nitrile,
-C=N).
M R peaks
(CDC1
lowed by g l p c
After
(1 C ,
T h e d e c r e a s e in e t h y l a e r y l a t e w a s
(3% SE 3 0 , 5' x 1 / 4 " , 58° C) o v e r a 12.8
2.9 h o u r s of r e a c t i o n t i m e the e t h y l
to 9 7 % at 12.8 h o u r s .
m i x t u r e a f t e r w o r k u p , as a b o v e , y i e l d e d
ethyl y-carbethoxy-y-cyanopimelate;
Into a 5 0 - m l . v o l u m e t r i c
1.77 M ) of e t h y l c y a n o a c e t a t e
flask
g.
aerylate
After
reaction
(0.08 m m ) .
(0.0089 m o l e s ,
0.179
and d i l u t e d to t h e m a r k
I n t o a second
to the m a r k w i t h
2 5 0 - m l . r o u n d b o t t o m flask e q u i p p e d w i t h m a g n e t i c
b a r , g r o u n d g l a s s s t o p p e r , r u b b e r s e p t e m , and
solution
hour
(0.0084 m o l e s ,
50-ml.
10.0 g.
vol­
acrylate
acetonitrile.
s o l u t i o n w a s added to a t h r e e
T o the e t h y l c y a n o a c e t a t e
fol­
(67%) of d i ­
(0.177 m o l e s , 3.54 M) of e t h y l
w a s d i r e c t l y w e i g h e d and d i l u t e d
The ethyl cyanoacetate
10.0
and 2.30 g.
w i t h t h e a d d i t i o n of a c e t o n i t r i l e .
17.7 g.
10.6 g.
b.p. 148-149° C
18-crown-6 was directly weighed
u m e t r i c flask
(M )
in the a b ­
the p a s s a g e of the 12.8 h o u r s of r e a c t i o n t i m e , the
M ) of
+
313
, i n t e r n a l T M S ) at - 1 1 7 . 9 4 4
had d e c r e a s e d by 9 0 % c o m p a r e d
II.
and
268, 222, 213, 194, 167, 108, 55,
S i m i l a r l y , the same r e a c t i o n w a s c o n d u c t e d
sence of 1 8 - c r o w n - 6 .
(ester
(8 H, m u l t i p l e t , -CH - C H ^ - C O O E t ) ,
and a b u n d a n t f r a g m e n t s m / e
period.
1
b.p.
necked
stirring
thermometer.
(0.172 m o l e s )
of
27
hot, dry p o t a s s i u m
15 m i n u t e s .
f l u o r i d e w a s added
The e t h y l a c r y l a t e
to 43°
C during
removed.
toward
fifteen m i n u t e s
the p o t a s s i u m
NMR
The flask w a s
to a t e m p e r a t u r e
The reaction mixture warmed
slowly d r o p p e d
C,
C,
and
but
A f t e r one h o u r and
the r e a c t i o n m i x t u r e w a s filtered
A sample w a s r e m o v e d
for v i n y l p r o t o n r e s o n a n c e
heated
immersed
of 2 0°
again t o 35°
room t e m p e r a t u r e .
fluoride.
added by
The r e a c t i o n m i x t u r e
this p e r i o d .
in an i c e - w a t e r b a t h , cooled
to stir for
s o l u t i o n w a s slowly
syringe over a ten-minute period.
rapidly
and allowed
corresponding
to r e m o v e
and e x a m i n e d
to e t h y l
by
acrylate.
N o v i n y l p r o t o n r e s o n a n c e w a s found and the sample w a s r e ­
turned
t o the r e a c t i o n m i x t u r e .
poured
into a separatory
The r e a c t i o n m i x t u r e w a s
funnel and 100
The m i x t u r e w a s shaken v i g o r o u s l y
arated.
combined,
The organic
4
on a rotary
after d i s t i l l a t i o n
evaporator
in v a c u o y i e l d e d
y-carbethoxy-y-cyanopimelate;
Similarly,
reaching
40°
1.5
300
under a vacuum,
b.p. 141-143°
ml.
were
and the
to give an o i l .
1 7 . 6 g. (63.4%)
sep­
The oil
of d i e t h y l
C (0.05 m m ) .
in the a b ­
A slow r i s e in t e m p e r a t u r e w a s n o t e d
C in thirty m i n u t e s .
an i c e - w a t e r b a t h , cooled
ter
layer
twice w i t h
the same r e a c t i o n w a s c o n d u c t e d
s e n c e of 1 8 - c r o w n - 6 .
added.
layer and e t h e r e x t r a c t s
dried over MgS0 , filtered
ether removed
moved.
and the o r g a n i c
The aqueous phase was extracted
of d i e t h y l e t h e r .
m l . of w a t e r
to a t e m p e r a t u r e
The reaction mixture warmed
h o u r s of r e a c t i o n
T h e flask w a s immersed
of 20°
C,
in
and r e ­
to room t e m p e r a t u r e .
Af­
t i m e , the m i x t u r e w a s filtered r e -
28
m o v i n g the p o t a s s i u m
fluoride.
A sample w a s r e m o v e d
and e x ­
amined by N M R for v i n y l p r o t o n r e s o n a n c e c o r r e s p o n d i n g
ethyl aerylate.
was returned
Vinyl proton resonance was found.
to the r e a c t i o n m i x t u r e .
a f t e r the w o r k u p , as a b o v e , y i e l d e d
y-carbethoxy-y-cyanopimelate;
III.
g.
flask 6.22
g.
sample
mixture
(36%) of
b.p. 138-140° C
Into a 25-ml. volumetric
The
The reaction
9.91
to
diethyl
(0.05mm).
(0.055 m o l e s ,
2.2 M ) e t h y l c y a n o a c e t a t e w a s d i r e c t l y w e i g h e d and d i l u t e d
the m a r k w i t h the a d d i t i o n of a c e t o n i t r i l e .
25-ml. volumetric
flask
5.0 g.
I n t o a second
(0.05 m o l e s , 2 M ) of e t h y l
late w a s d i r e c t l y w e i g h e d and d i l u t e d t o the m a r k w i t h
trile.
necked
The ethyl cyanoacetate
to
acry-
acetoni­
s o l u t i o n w a s added to a three
1 0 0 - m l . r o u n d b o t t o m flask e q u i p p e d w i t h a m a g n e t i c
s t i r r i n g b a r , g r o u n d g l a s s s t o p p e r , r u b b e r s e p t u m , and
mometer.
T o the e t h y l c y a n o a c e t a t e
solution
1.30
g.
(0.0049
m o l e s , 0.098 M) of 1 8 - c r o w n - 6 w a s added and a l l o w e d to
for five m i n u t e s .
T h e n 2.9 g.
ther­
stir
(0.05 m o l e s ) of d r y , h o t p o ­
t a s s i u m f l u o r i d e w a s added and a l l o w e d t o stir for five m i n ­
utes.
T h e e t h y l a c r y l a t e s o l u t i o n w a s slowly added by
syringe
o v e r a t w e n t y - m i n u t e p e r i o d w i t h the r e a c t i o n n o t h e a t i n g
35° C.
T h e r e a c t i o n w a s m o n i t o r e d by g l p c
58° C) for d i s a p p e a r a n c e
jection
(3% SE 3 0 . 5' x
of e t h y l a c r y l a t e .
peak size of the e t h y l a c r y l a t e w a s noted
to
1/4",
N o c h a n g e in the
from the i n i t i a l i n ­
(reaction time 25 m i n u t e s ) over t h e n e x t t h r e e h o u r s .
T h e r e a c t i o n m i x t u r e w a s s t i r r e d an a d d i t i o n a l n i n e h o u r s , at
w h i c h t i m e , the r e a c t i o n m i x t u r e w a s p o u r e d i n t o 100 m l . of
29
w a t e r and stirred.
aratory
The aqueous m i x t u r e w a s p o u r e d
funnel and the o r g a n i c
phase was extracted
organic
MgSO^,
twice w i t h
filtered
a n o a c e t a t e b . p . 40° C
cyanoacetate
148° C
(0.1 mm)
5.8 g.
and
ethyl
10.0 g.
Condensation
flask
1.30
the a d d i t i o n of a c e t o n i t r i l e .
g.
8.81 g.
(0.055 m o l e s ,
(0.0049 m o l e s , 0.19 M)
and d i l u t e d
Into a second
to the m a r k
25-ml.
ethyl malonate,
to the m a r k w i t h a c e t o n i t r i l e .
18-crown-6
ed 1 0 0 - m l . round b o t t o m
s o l u t i o n w a s added
to the d i e t h y l m a l o n a t e
to a three
over a s i x - m i n u t e p e r i o d .
over a t h i r t y - m i n u t e p e r i o d
Then
added
to stir for
s o l u t i o n w a s added by
in f o r t y - f i v e m i n u t e s .
slowly
The
five
syringe
The r e a c t i o n m i x t u r e h e a t e d
to 40° C, a f t e r w a r d s
neck­
bar,
fluoride was
s o l u t i o n and allowed
The e t h y l a c r y l a t e
ing to room t e m p e r a t u r e
The d i ­
and t h e r m o m e t e r .
(0.055 m o l e s ) of d r y , hot p o t a s s i u m
with
directly
flask e q u i p p e d w i t h a s t i r r i n g
s t o p p e r , r u b b e r septum,
of
volumetric
(0.1 m o l e s , 4 M) of e t h y l a c r y l a t e w a s
and d i l u t e d
minutes.
(64% based on
cy­
ycarbethoxy-y-cyanopimelate
and D i e t h y l M a l o n a t e
18-crown-6 were directly weighed
3.2 g.
distillation
(0.08 m m ) .
2.2 M) d i e t h y l m a l o n a t e
ground g l a s s
The oil after
and
Into a 2 5 - m l . v o l u m e t r i c
weighed
over
(0.021 m o l e s ) of r e c o v e r e d , e t h y l
r e a c t e d ) of d i e t h y l
Ethyl Acrylate
flask
dried
The
and the e t h e r r e m o v e d on a
to give an o i l .
2.4 g.
aqueous
300 m l . of d i e t h y l e t h e r .
under a v a c u u m ,
in v a c u o y i e l d e d
I.
The
layer and e t h e r e x t r a c t s w e r e combined,
rotary e v a p o r a t o r
b.p.
layer s e p a r a t e d .
into a s e p -
slowly
cool­
reaction
30
was m o n i t o r e d
by glpc
(3% SE 30, 5' x 1/4",
a p p e a r a n c e of ethyl a c r y l a t e .
58
C) for
dis­
A steady d e c l i n e w a s noted
ethyl acrylate concentration
for 2.9 h o u r s of r e a c t i o n
w h e r e b y , no further d e c r e a s e
in e t h y l a c r y l a t e w a s n o t e d .
ter t w e n t y - o n e h o u r s of r e a c t i o n
was poured
into 100 m l . of w a t e r and s t i r r e d .
m i x t u r e w a s poured
layer s e p a r a t e d .
into a s e p a r a t o r y
tracts w e r e c o m b i n e d ,
The o r g a n i c
mm)
[lit.
infrared
(CDC1 ,
3
1
1
7
i n t e r n a l TMS)
(8 H, s i n g l e t ,
CH^-);
214,
(CCl^)
1735 c m
6 4.2
2
(58%)
(0.05
(12 m m )
-CH Me),
(12 H,
peaks
in the
in the e t h y l
to stir over a four-day
the p a s s a g e of this t i m e , the r e a c t i o n
up, as a b o v e , y i e l d e d
ethyl malonate
32° C
5.29
g.
2.24
triplet,
late c o n c e n t r a t i o n over a t h r e e - h o u r m o n i t o r i n g p e r i o d .
After
] ;
29.
N o d e c r e a s e w a s noted
r e a c t i o n m i x t u r e w a s allowed
1 3 5
at 6
2
the same r e a c t i o n w a s c o n d u c t e d
sence of 1 8 - c r o w n - 6 .
10.5 g.
fragments, m/e 315, 260, 241,
1 9 5 , 1 8 6 , 153, 140, 1 2 7 , 55, and
Similarly,
an
(ester C = 0 ) ; N M R
and at 6 1.2
m a s s s p e c t r u m of a b u n d a n t
ex­
to give
b.p. 142-145° C
(8 H, q u a r t e t ,
-CH -CH -COOEt)
2
- 1
with
filtered u n d e r a v a c ­
b . p . 2 1 7 - 2 1 9 ° C/20 mm, b . p . 215° C
absorption
organic
layer and e t h e r
in v a c u o y i e l d e d
of d i e t h y l y, y - d i c a r b e t h o x y p i m e l a t e ;
Af­
aqueous
twice
on a rotary e v a p o r a t o r
The oil after d i s t i l l a t i o n
time,
mixture
funnel and the
dried over M g S O ^ ,
and the e t h e r removed
oil.
The
The a q u e o u s p h a s e w a s e x t r a c t e d
300 m l . of d i e t h y l e t h e r .
uum,
t i m e , the r e a c t i o n
in
acry­
The
period.
after the w o r k
(0.022 m o l e s ) of r e c o v e r e d
(0.08 m m ) , and 3.12 g
ab­
(36% based
di­
on r e -
31
covered
b.p.
diethyl malonate)
90° C
absorption
(0.05 mm)
(CC1 )
4
[lit.
1735 c m "
t e r n a l TMS) at 6 4.19
triplet, - C - H ) ,
and at 6 1.22
+
(M )
of d i e t h y l a - c a r b e t h o x y
and
1 3 5
1
b . p . 157-158
(ester C = 0 ) ; NMR p e a k s
2
(CDC1 ,
in­
3
at <S 3.46
(4 H, m u l t i p l e t ,
(9 H, t r i p l e t , C H ^ - ) ;
and a b u n d a n t
(12 m m ) ] ; infrared
(6 H q u a r t e t , C H M e ) ,
62.6-2.0
glutarate;
(1 H,
-CH -CH -COOEt),
2
2
m a s s spectrum,
m/e
260
fragments m / e 2 1 5 , 169, 1 3 3 , 115, 43, and
29.
II.
Into a 2 5 - m l . v o l u m e t r i c
flask
8.81 g.
(0.055 m o l e s ,
2.2 M ) of d i e t h y l m a l o n a t e w a s d i r e c t l y w e i g h e d
to the m a r k w i t h a c e t o n i t r i l e .
flask
5.0 g.
weighed
Into a second
and diluted
s o l u t i o n was added
ground glass
s t o p p e r , rubber septum,
diethyl malonate
solution
1.30
g.
18-crown-6 w a s added and allowed
(0.055 m o l e s )
and a l l o w e d
to stir
late s o l u t i o n w a s slowly
period.
To
the
to stir for five m i n u t e s .
fluoride
The e t h y l
added by s y r i n g e over a
was
acry­
five-minute
to stir for three h o u r s .
into 100 m l . of w a t e r
The a q u e o u s m i x t u r e w a s p o u r e d
layer s e p a r a t e d .
twice w i t h
bar,
(0.0049 m o l e s , 0.0098 M )
T h e n the r e a c t i o n m i x t u r e w a s p o u r e d
phase was extracted
100-ml.
and t h e r m o m e t e r .
for five m i n u t e s .
tory f u n n e l and the o r g a n i c
directly
stirring
of dry, hot p o t a s s i u m
The s o l u t i o n w a s allowed
and s t i r r e d .
volumetric
The d i ­
to a three n e c k e d
flask e q u i p p e d w i t h a m a g n e t i c
added
25-ml.
to the mark w i t h a c e t o n i t r i l e .
round b o t t o m
3.2 g.
diluted
(0.05 m o l e s , 2 M) of e t h y l a c r y l a t e w a s
ethyl m a l o n a t e
Then
and
into a
The
separa-
aqueous
300 m l . of d i e t h y l e t h e r .
The
32
organic layer and ether extracts were combined, dried
MgSO^, filtered under a vacuum, and the ether rem
rotary evaporator to five an oil. The oil after
in vacuo yielded 7.23 g. (62%) of diethyl a-carb
b.p. 97.5° C (0.08 mm) and 2.91 g. of pot
material was redistilled and yielded 1.32 g. (8%)
y, y-dicarbethoxypimelate b.p. 146° C (0.08 mm).
Ethyl Acrylate and Cyclohexanone Condensation
A three necked 100 ml. round bottom flask eq
a magnetic stirring bar, ground glass stopper, rubbe
and thermometer was charged with 10.11 g (0.103 mo
cyclohexanone and 2.70 g. (0.0102 moles) of 18-crow
ml. of acetonitrile. To this solution was added
moles) of dry, hot potassium fluoride and allowed
one hour. Then, 10.3 g. (0.103 moles) of ethyl
slowly added by syringe over a 45-minute period.
ture increase was noted at all. After two days
finitive change in the reaction mixture was noted.
a reflux condenser equipped with a drying tube of
chloride was added to the reaction vessel. The ma
refluxed for five days over which time the reaction
turned a dark brown. Refluxing was stopped and the
was poured into 150 ml. of water and stirred.
mixture was poured into a separatory funnel and the
layer separated. The aqueous phase was extracted tw
125 ml. of diethyl ether. The organic layer and
33
tracts w e r e combined,
dried
and the e t h e r removed
on a rotary e v a p o r a t o r
The oil after d i s t i l l a t i o n
over M g S 0 ,
4
in v a c u o y i e l d e d
m o l e s ) of c y c l o h e x a n o n e and
hexanepropionate;
C
(0.13 mm)
C=0) and
6 3.95
1735 c m
- 1
g.
-CH ~Me)
mm)
[lit.
(CC1 )
3
b . p . 145° C
1708 c m "
4
peaks
1 3 7
1
(ketone C=0) and
CH ~);
s p e c t r a , m / e 29 8
1728 c m "
1
and at 6 1.23
+
(M )
Knoevenagel
and B e n z a l d e h y d e
2.64 g.
weighed
g.
at
multiplet)
g.
(9%) d i ­
(0.15
absorption
(ester C = 0 ) ; NMR
(6 H,
CH ~Me),
2
triplet,
fragments
29.
A large
No
are
fur­
quantity
flask.
Condensations
Condensation
Into a 5 0 - m l . v o l u m e t r i c
and
1.99
and a b u n d a n t
in the d i s t i l l a t i o n
6.61
(ketone
(4 H, q u a r t e t ,
ther a t t e m p t s w e r e m a d e to improve y i e l d s .
of b e n z a l d e h y d e ,
1
96-100°
+
2 0 7 , 1 9 8 , 189, 165, 1 5 2 , 1 2 3 , 6 7 , 55, and
Malononitrile
b.p.
(13 H,
(0.05 m m ) ] ; infrared
(16 H, m u l t i p l e t )
of tar r e m a i n e d
1 3 6
( d i p r o p i o n a t e ) ; b . p . 155° C
at 6 2 . 7 - 1 . 5
253,
2-oxocyclo-
(internal, TMS)
and y i e l d e d
3
mass
lit.
(0.024
m a s s s p e c t r a , m / e 198 ( M ) .
( C D C 1 , i n t e r n a l TMS) at 6 4.14
3
2.1 g.
(CCl^) 1715 cm""
(3 H, t r i p l e t , - C H ) ;
2-oxocyclohexanebis
to give an o i l .
at 6 2.5-1.2
2
The pot m a t e r i a l w a s r e d i s t i l l e d
ethyl
(0.3 mm)
abosrptions
under a vacuum,
(8%) of e t h y l
(ester C = 0 ) ; NMR p e a k s
(2 H, q u a r t e t ,
and at 6 1.05
1.20
b.p. 104-109° C
; infrared
filtered
flask 10.6 g.
(0.1 m o l e s , 2 M) of
(0.1 m o l e s , 2 M )
malononitrile,
(0.01 m o l e s , 0.2 M ) of 18-crown-6 w e r e
and sealed w i t h a r u b b e r
septum.
Then dry
directly
benzene
34
w a s added
solution
to the v o l u m e t r i c by canulla
shaken until h o m o g e n e o u s .
round b o t t o m
to the m a r k and
A three necked
flask e q u i p p e d w i t h a m a g n e t i c
t h e r m o m e t e r , rubber septum,
the
100-ml.
stirring
bar,
and c o n d e n s e r w i t h a d r y i n g
tube
of c a l c i u m c h l o r i d e w a s charged w i t h the b e n z e n e
solution.
Then
fluoride
1.55 g.
added
(0.026 m o l e s ) of dry, hot p o t a s s i u m
to the b e n z e n e s o l u t i o n and stirred v i g o r o u s l y .
solution
immediately
a rise in t e m p e r a t u r e
68° C.
The
followed by glpc
the d i s a p p e a r a n c e
action
(3% S E C - 3 0 , 5
of b e n z a l d e h y d e .
time, a s u b s t a n t i a l d e c r e a s e
(comparing
1
x 1/4",
The
100° C)
in b e n z a l d e h y d e was
at a g i v e n
A f t e r one hour r e a c t i o n
the o r g a n i c
twice w i t h
layer s e p a r a t e d .
e t h e r e x t r a c t s w e r e combined,
a vacuum,
dried
The solid
potassium
funnel
The o r g a n i c
over M g S O ^ ,
(77%) of b e n z y l i d e n e m a l o n o n i t r i l e ;
and
extracted
layer
and
filtered
on a rotary e v a p o r a t o r
after s u b l i m a t i o n
reac­
stirred.
The a q u e o u s p h a s e w a s
and the ether removed
a red solid.
11.9 g.
into a s e p a r a t o r y
300 m l . of d i e t h y l e t h e r .
noted
t i m e , the
i n t o 100 m l . of w a t e r and
T h e a q u e o u s m i x t u r e w a s poured
for
reaction
time to the i n i t i a l peak area of b e n z a l d e h y d e b e f o r e
tion m i x t u r e w a s p o u r e d
reac­
A f t e r ten m i n u t e s of r e ­
the peak area of b e n z a l d e h y d e
fluoride w a s a d d e d ) .
by
formation
of a second p h a s e w h i c h was w a t e r was also n o t e d .
tion w a s
The
turned a d e e p red color a c c o m p a n i e d
to a p p r o x i m a t e l y
was
in_ v a c u o
under
to
yielded
m . p . 81-83° C
138
[lit.
m . p . 8 3 . 5 - 8 4 . 0 ° C ] ; infrared
(KBr) 2225 c m "
1
spectrum
(nitrile, C = N ) ; NMR p e a k s
absorption
(CDCl^,
internal
give
35
TMS) at 6 8.2-7.2
m/e,
154
+
(M )
Approximately
(6 H, m u l t i p l e t , p h e n y l — C H = ) ;
and abundant
fragments
left in the
m a t i o n a p p a r a t u s as a gum w h i c h could not be
by glpc
The d e c r e a s e
(3% S E C - 3 0 , 5' x 1/4",
whereby,
subli­
in the
in b e n z a l d e h y d e w a s
The
stirred
for nine days and after the w o r k u p , as
yielded
13.1 g.
(84%) b e n z y l i d e n e m a l o n o n i t r i l e ,
Into a 5 0 - m l . v o l u m e t r i c
of c y c l o h e x a n o n e ,
and
2.64 g.
weighed
6.61
g.
above,
m . p . 81-83°
C.
Condensation
flask 9.8
g.
(0.1 m o l e s , 2 M)
(0.1 m o l e s , 2 M) of
malononitrile,
(0.01 m o l e s , 0.2 M) of 18-crown-6 w e r e
and sealed w i t h a rubber
period
reaction
mixture
and C y c l o h e x a n o n e
ab­
followed
100° C) over a 16.8 hour
the b e n z a l d e h y d e had slowly d e c r e a s e d .
Malononitrile
32.
characterized.
the same r e a c t i o n w a s c o n d u c t e d
sence of 1 8 - c r o w n - 6 .
spectrum,
1 2 7 , 103, 76, 51, and
1.5 g. of solid m a t e r i a l w a s
Similarly,
mass
septum.
directly
Then dry b e n z e n e
was
added to the v o l u m e t r i c by c a n u l l a to the m a r k and the
solu­
tion s h a k e n u n t i l h o m o g e n e o u s .
round-
A three n e c k e d
bottom
flask e q u i p p e d w i t h a m a g n e t i c
rubber
septum,
(0.026 m o l e s ) of dry, hot p o t a s s i u m
benzene solution
diately
changed
in t e m p e r a t u r e
stirring bar,
and c o n d e n s e r w i t h a d r y i n g
c h l o r i d e w a s charged w i t h the b e n z e n e
tube of
solution.
color to a dark y e l l o w ,
followed by g l p c
calcium
Then
60° C.
The s o l u t i o n
accompanied
1.55
to
g.
the
imme­
by a rise
The f o r m a t i o n of a
second p h a s e , w h i c h w a s w a t e r , w a s also n o t e d .
was
thermometer,
f l u o r i d e w a s added
and stirred v i g o r o u s l y .
to a p p r o x i m a t e l y
100-ml.
(3% S E C - 3 0 , 5' x 1/4",
The
reaction
89° C) for
the
36
disappearance
decrease
of c y c l o h e x a n o n e .
After
ten m i n u t e s , a
in the c y c l o h e x a n o n e was noted
area of c y c l o h e x a n o n e
(comparing
at a given r e a c t i o n
large
the
time to the
peak area of c y c l o h e x a n o n e b e f o r e p o t a s s i u m
peak
initial
fluoride was
added).
A f t e r one h o u r of r e a c t i o n t i m e , the r e a c t i o n m i x t u r e w a s
tered
to r e m o v e a y e l l o w c r y s t a l l i n e m a t e r i a l , m . p .
124.5-129°
C, w h i c h w a s shown to be a n o v e l 1:2 c r o w n - m a l o n o n i t r i l e
plex
(to be d i s c u s s e d
later in further d e t a i l ) .
m i x t u r e w a s then p o u r e d
The a q u e o u s m i x t u r e w a s p o u r e d
the o r g a n i c
twice w i t h
layer s e p a r a t e d .
into a s e p a r a t o r y
300 m l . of d i e t h y l e t h e r .
der a v a c u u m ,
and the e t h e r removed
give an o i l .
The oil after d i s t i l l a t i o n
[lit.
1 3 9
b.p. 137-138° C
+
(M )
and
layer
and
filtered
un­
b.p. 69-70° C
(10 m m ) ] ; infrared
to
10.5
(0.5
absorption
-1
(neat) 2235 cm
tiplet)
extracted
in v a c u o y i e l d e d
-1
(nitrile, C=N) and
C = C ) : NMR p e a k s
and
on a rotary e v a p o r a t o r
(72%) of c y c l o h e x y l i d e n e m a l o n o n i t r i l e ;
mm)
reaction
funnel
The organic
dried o v e r M g S O ^ ,
com­
stirred.
The a q u e o u s p h a s e w a s
ether e x t r a c t s w e r e combined,
g.
The
into 1 0 0 - m l . of w a t e r and
fil­
1599 cm
(double
( C D C 1 , i n t e r n a l TMS) at 6 2.8-2.4
3
6 2.1-1.4
and a b u n d a n t
bond,
(4 H, m u l -
(6 H, m u l t i p l e t ) ; m a s s s p e c t r a , m / e
fragments
146
1 3 1 , 1 1 8 , 105, 9 2 , 8 1 , 6 9 , 55, and
41.
Similarly,
the same r e a c t i o n w a s c o n d u c t e d
sence of 1 8 - c r o w n - 6 .
lowed by glpc
The d e c r e a s e
in the
in c y c l o h e x a n o n e w a s
(3% S E C - 3 0 , 5' x 1/4, 89° C) over a one
period, whereby
the c y c l o h e x a n o n e had slowly d e c r e a s e d
ab­
fol­
hour
steadily.
37
The r e a c t i o n m i x t u r e w a s stopped
up, as a b o v e , y i e l d e d
trile, b.p. 67-68° C
Ethylcyanoacetate
9.9
g.
(68%) of
cyclohexylidenemalononi-
(0.5 m m ) .
and B e n z a l d e h y d e
Into a 5 0 - m l . v o l u m e t r i c
of b e n z a l d e h y d e ,
after one hour and the w o r k
11.3 g.
Condensation
flask
10.6 g.
(0.1 m o l e s , 2 M)
(0.1 m o l e s , 2 M) of e t h y l
cyanoacetate,
and 2.6 4 g.
(0.01 m o l e s , 0.2 M) of 18-crown-6 w e r e
directly
weighed
sealed w i t h a rubber
benzene
and
w a s added
to the v o l u m e t r i c
septum.
by c a n u l l a
lution shaken u n t i l h o m o g e n e o u s .
bottom
Then
1.55
added
g.
(0.026 m o l e s )
immediately
followed by glpc
disappearance
stirring bar,
of dry, hot p o t a s s i u m
solution
turned
a rise in t e m p e r a t u r e
was
and stirred
a deep
red
to a p p r o x i m a t e l y
of b e n z a l d e h y d e .
the o r g a n i c
phase was extracted
organic
The
filtered u n d e r a v a c u u m ,
rotary
evaporator
The
100° C) for
by
the
a
reac­
water
into a s e p a r a The
aqueous
300 m l . of d i e t h y l e t h e r .
layer and e t h e r e x t r a c t s w e r e c o m b i n e d ,
MgSO^,
was
reaction
into 100 m l . of
layer s e p a r a t e d .
twice w i t h
fluoride
A f t e r six h o u r s of
The a q u e o u s m i x t u r e w a s p o u r e d
funnel and
solution.
A f t e r twelve m i n u t e s only
tion, the r e a c t i o n m i x t u r e w a s poured
tory
round-
color a c c o m p a n i e d
60° C.
so­
thermometer,
vigorously.
(3% S E C - 3 0 , 5' x 1/4",
trace of b e n z a l d e h y d e w a s p r e s e n t .
and s t i r r e d .
100-ml.
stopper w a s charged w i t h the b e n z e n e
to the b e n z e n e
solution
to the m a r k and the
A three-necked
flask e q u i p p e d w i t h a m a g n e t
and g r o u n d - g l a s s
T h e n dry
dried
The
over
and the ether r e m o v e d on a
to give a solid.
The solid after
sublima-
38
tion in v a c u o y i e l d e d
16.3 g.
(81%) of e t h y l
benzylidene-
30
c y a n o a c e t a t e ; m . p . 48-49° C [lit.
absorptions
C=0),
and
(KBr) 2225 c m "
1615 c m
t e r n a l TMS)
multiplet,
- 1
1
m . p . 50-52
(nitrile, C = N ) , 1725 c m "
(double b o n d , C = C ) ; NMR p e a k s
at 6 8.28
phenyl-),
(1 H, s i n g l e t , H - C = C ) ,
6 4.4
(2 H, q u a r t e t ,
sence of
+
(M )
(5 H,
and
and
6
abundant
in the
The d e c r e a s e in b e n z a l d e h y d e w a s
by glpc
(3% S E C - 3 0 , 5' x 1/4",
whereby
the b e n z a l d e h y d e
1.33
51.
the same r e a c t i o n w a s c o n d u c t e d
18-crown-6.
(ester,
(CDCl^, i n ­
-CJ^Me),
at 2 0 0 , 1 7 2 , 156, 1 2 8 , 1 0 2 , 7 7 , and
Similarly,
1
6 8.1-7.3
(3 H, t r i p l e t , CH.,-); m a s s spectrum, m / e 201
fragments
C ] ; infrared
100° C) over a six-day
followed
period,
six
days
the r e a c t i o n m i x t u r e w a s w o r k e d u p , as a b o v e , and y i e l d e d
9.18
g.
had slowly d e c r e a s e d .
ab­
(46%) of e t h y l b e n z y l i d e n e c y a n o a c e t a t e , m . p . 48-49° C.
Diethyl Malonate
and B e n z a l d e h y d e
Into a 5 0 - m l . v o l u m e t r i c
of b e n z l a d e h y d e ,
and
After
2.6 4 g.
weighed
flask
10.6 g.
(0.1 m o l e s , 2 M)
(0.1 m o l e s , 2 M) of d i e t h y l
(0.01 m o l e s , 0.2M)
of 18-crown-6 w e r e
and sealed w i t h a rubber
w a s added
solution
16.0 g.
Condendation
septum.
malonate,
directly
T h e n dry
benzene
to the v o l u m e t r i c by c a n u l l a to the m a r k and
shaken u n t i l h o m o g e n e o u s .
round b o t t o m
A three necked
flask e q u i p p e d w i t h a m a g n e t i c
c h a r g e d w i t h the b e n z e n e
of d r y , hot p o t a s s i u m
solution.
Then
100-ml.
stirring
t h e r m o m e t e r , ground g l a s s s t o p p e r , and D e a n - S t a r k
1.55
g.
the
bar,
trap w a s
(0.026
f l u o r i d e w a s added to the b e n z e n e
tion and stirred v i g o r o u s l y .
The s o l u t i o n w a s heated
moles)
solu­
to r e -
30
fluxing w i t h
the
internal
t w e l v e h o u r s of r e a c t i o n
Stark trap.
and
After
temperature
reaching
92° C.
t i m e , w a t e r w a s noted
in the
w a s then stopped and poured
layer
separated.
The organic
1
6 7.74
(5 H, m u l t i p l e t ,
phenyl),
with
ex­
8.1 g.
(0.11 mm)
absorption
at
fragments
6 4.6-4.0
-CH^):
vacuum,
to g i v e an o i l .
(CC1 )
(33%)
[lit.
1 4 0
1730 c m
4
(1 H, singlet, H - C = C - ) ,
(6 H, sextet,
+
twice
(double bond, C = C ) ; NMR p e a k s
i n t e r n a l T M S ) at
and
in v a c u o y i e l d e d
b.p. 120-124° C
1630 cm""
( M ) , and a b u n d a n t
organic
4
(4 m m ) ] ; infrared
6 1.5-1.1
aqueous
dired over MgSC> , f i l t e r e d u n d e r a
The o i l after d i s t i l l a t i o n
and
reaction
layer and ether
and the e t h e r r e m o v e d on a r o t a r y e v a p o r a t o r
ethyl benzalmalonate;
black
The
funnel and the
The a q u e o u s p h a s e w a s e x t r a c t e d
tracts were combined,
t e r , C = 0 ) , and
The
into 100 m l . of w a t e r .
into a s e p a r a t o r y
300 m l . of d i e t h y l e t h e r .
140-142° C
Dean-
three d a y s , the s o l u t i o n had turned
0.7 m . of w a t e r w a s in the D e a n - S t a r k t r a p .
m i x u t r e w a s poured
After
at
(4 H, o c t e t ,
of
b.p.
- 1
(es­
(CDC1 ,
3
6 7.6-7.2
-CH -Me),
2
m a s s spectrum, m / e
248
203, 1 7 4 , 1 5 8 , 1 3 1 , 1 3 0 , 1 0 2 , 7 7 ,
29.
Similarly,
the same r e a c t i o n w a s c o n d u c t e d
sence of 1 8 - c r o w n - 6 .
t r a p and
diethyl
N o w a t e r w a s found
in the
in the
ab­
Dean-Stark
the w o r k u p , as a b o v e , y i e l d e d o n l y starting
material,
malonate.
Alkylations
Diethyl Malonate with Benzyl
Bromide
Into a 5 0 - m l . v o l u m e t r i c
flask 9.4
g.
(0.059 m o l e s .
40
1.18 M ) of d i e t h y l m a l o n a t e ,
b e n z y l b r o m i d e and
1.55 g.
were directly weighed
The acetonitrile
geneous.
(0.59 m o l e s , 1.18 M )
(0.0058 m o l e s , 0.12 M ) of
and d i l u t e d
to the m a r k w i t h
solution was thoroughly
A three necked
with a magnetic
10.0 g.
stirring
(0.23 m o l e s ) od d r y , hot p o t a s s i u m
to the a c e t o n i t r i l e
solution and
action was monitored
the d i s a p p e a r a n c e
by g l p c
to removed
solution.
After
the p o t a s s i u m
The
reaction
and
The solid m a t e r i a l
was
The a q u e o u s m i x t u r e w a s p o u r e d
twice with
diethyl ether.
The e t h e r e x t r a c t s w e r e c o m b i n e d ,
for
reac­
fluoride
f u n n e l and e x t r a c t e d
in­
300 m l . of
dried
over
f i l t e r e d u n d e r a v a c u u m , and the e t h e r r e m o v e d o n a
rotary evaporator
in v a c u o y i e l d e d
malonate
40° C
to g i v e an o i l .
1.1 g.
The oil a f t e r
(0.11 mm)
(0.11 m m ) and
[lit.
(CC1 )
4
1 4 1
9.14
b.p. 150-160° C
1735 c m "
6 7.2
1
distillation
(0.007 m o l e s ) of r e c o v e r e d
g.
diethyl
(63% based on
d i e t h y l m a l o n a t e ) of d i e t h y l b e n z y l m a l o n a t e ;
T M S ) at
added
The r e ­
41 h o u r s of
to a s e p a r a t o r y
tion
rub­
Then
fluoride was
be d e t e c t e d .
into 100 m l . of w a t e r .
washed with diethyl ether.
MgSO^,
equipped
(3% SE 3 0 , 5" x 1/4", 1 0 0 ° C)
tion t i m e , no b e n z y l b r o m i d e could
then p o u r e d
flask
homo­
stirred v i g o r o u s l y .
of b e n z y l b r o m i d e .
m i x t u r e w a s filtered
acetonitril
b a r , ground g l a s s s t o p p e r , and
ber septum w a s c h a r g e d w i t h the a c e t o n i t r i l e
13.5 g.
18-crown-
shaken u n t i l
1 0 0 - m l . round b o t t o m
of
recovered
b.p. 100-105° C
(7 m m ) ] ; infrared
(ester C = 0 ) ; NMR p e a k s
(5 H, singlet, A r H ) , at
6 4.1
(CDC1 ,
3
(4 H,
absorp­
internal
quartet.
41
-CH -Me), a t 6 3.68 (1 H, q u a r t e t , C-H), a t 6 3.20 (2 H, doub­
2
l e t , Ar-CH ~), and a t 5 1.1
2
(6 H, t r i p l e t , CII^-):
mass s p e c ­
+
trum, m/e 250 (M ) and abundant fragments 205, 176, 159, 148,
131, 103, 9 1 , 77, 5 1 , and 29.
There was 2.72 g. of p o t m a t e ­
r i a l remaining which was r e d i s t i l l e d t o g i v e 1.34 g.
(12.1%
based on r e c o v e r e d d i e t h y l malonate) of d i e t h y l d i b e n z y l m a l o n a t e ; b . p . 143-148° C (0.24 m) [ l i t .
infrared absorptions
cm
- 1
(CCI4)
1735 c m
- 1
(double bond, p h e n y l ) ; NMR peaks
1 4 2
234-5 (23 mm)];
( e s t e r , C=0) and 1601
(CDCI3,
i n t e r n a l TMS)
a t (S 7.2 (10 II, s i n g l e t . Aril), a t 6 4 . 1 (4 H, q u a r t e t , -CH -Me) ,
2
a t <S 3.24 (4 II, s i n g l e t , -CH ~) , and a t 6 1.1
2
CH3-);
+
(6 H, t r i p l e t ,
mass spectrum, m/e 340 (M ) and abundant
fragments
295, 249, 203, 192, 115, 9 1 , 6 5 , and 29.
S i m i l a r l y , t h e same r e a c t i o n was conducted i n t h e a b ­
sence of 18-crown-6.
No change i n benzyl bromide was noted
by g l p c (3% SE-30, 5' x 1/4",
100° C) and t h e work up, as
above, y i e l d e d only t h e s t a r t i n g m a t e r i a l d i e t h y l m a l o n a t e .
D i e t h y l Malonate with Benzyl C h l o r i d e
I n t o a 50-ml. v o l u m e t r i c f l a s k 9.4 g.
1.18 M) of d i e t h y l m a l o n a t e , 7.4 g.
benzyl c h l o r i d e and 1.58 g.
(0.059 moles,
(0.059 moles, 1.18 M) of
(0.006 m o l e s , 0.12 M) of 18-crown-6
were d i r e c t l y weighed and d i l u t e d t o t h e mark with a c e t o n i t r i l e .
The a c e t o n i t r i l e s o l u t i o n was t h o r o u g h l y shaken u n t i l homo­
geneous.
A t h r e e - n e c k e d 100-ml. round bottom f l a s k
equipped
with a magnetic s t i r r i n g b a r , ground g l a s s s t o p p e r , and r u b ­
b e r septum was charged with t h e a c e t o n i t r i l e s o l u t i o n .
Then
42
13.5 g.
(0.23 m o l e s ) of dry, hot p o t a s s i u m
to the a c e t o n i t r i l e
s o l u t i o n and stirred v i g o r o u s l y .
action w a s m o n i t o r e d
by glpc
for the d i s a p p e a r a n c e
(3% S E - 3 0 , 5' x 1/4",
of b e n z y l c h l o r i d e .
After
r e a c t i o n , only a trace of b e n z y l c h l o r i d e
The r e a c t i o n m i x t u r e w a s filtered
fluoride and then p o u r e d
300 m l . of d i e t h y l e t h e r .
dried over M g S O ^ ,
distillation
malonate
gave
40° C
covered
and
N o change
(3% S E - 3 0 , 5' x 1/4",
above, yielded
were directly weighed
105-110
in the
in b e n z y l c h l o r i d e w a s
ab­
noted
the w o r k u p , as
malonate.
Iodide
flask
2.50 M) of d i e t h y l m a l o n a t e , 9.2 g.
1.7 g.
diethyl
dibenzylmalonate.
100° C) and
Into a 2 5 - m l . v o l u m e t r i c
i o d i d e , and
upon
(10% b a s e d on r e ­
only the s t a r t i n g m a t e r i a l d i e t h y l
Diethyl Malonate with Methyl
methyl
1.00 g.
re­
recovered
the same r e a c t i o n w a s c o n d u c t e d
18-crown-6.
with
combined,
The oil
(56% based on
of d i e t h y l
mixture
and the ether
of d i e t h y l b e n z y l m a l o n a t e , b . p .
diethyl malonate)
sence of
8.1 g.
solid
twice
(0.008 m o l e s ) of r e c o v e r e d
T h e r e w a s a l s o isolated
Similarly,
by g l p c
g.
(0.1 mm)
diethyl malonate)
(0.15 m m ) .
1.25
The
The e h t e r e x t r a c t s w e r e
to give an o i l .
of
detected.
The a q u e o u s
filtered under a v a c u u m ,
re­
potassium
funnel and e x t r a c t e d
m o v e d on a rotary e v a p o r a t o r
The
186 h o u r s
into 100 m l . of w a t e r .
into a s e p a r a t o r y
added
100° C)
could be
to remove the
material was washed with diethyl ether.
w a s poured
fluoride was
10.0 g.
(0.0624 m o l e s ,
(0.0648 m o l e s , 2.59 M )
(0.0064 m o l e s , 0.26 M) of
and d i l u t e d
to the m a r k w i t h
of
18-crown-6
acetonitrile.
43
The a c e t o n i t r i l e
geneous.
s o l u t i o n was t h o r o u g h l y
The a c e t o n i t r i l e
round b o t t o m
flask,
w i t h a rubber
solution w a s poured
10.9 g.
sium f l u o r i d e w a s added,
and the round b o t t o m
After
, 90° C) for d i s a p p e a r a n c e
58 d a y s , the r e a c t i o n m i x t u r e
The r e a c t i o n m i x t u r e w a s poured
funnel and e x t r a c t e d
twice w i t h
e t h e r e x t r a c t s w e r e combined,
an o i l .
SE-30,
samples
stopped.
and
separatory
on a rotary e v a p o r a t o r
in v a c u o at 41°
g.
and
under
to give
(0.1 mm)
diethyl
3%
to c o n s i s t of 13%
(53.4% based
diethyl methylmalonate.
of p u r e m a t e r i a l w e r e used
C
The
internal standard,
the m i x t u r e
(0.797 g.) and 5.33
covered d i e t h y l m a l o n a t e )
that
300 m l . of d i e t h y l e t h e r .
(bromocyclohexane
5' x 1/4", 90° C) showed
diethyl malonate
glpc
diethyl
showed
into a
g. of a m i x t u r e of d i e t h y l m a l o n a t e
Glpc
by
dried over M g S O ^ , filtered
and the e h t e r removed
methylmalonate.
of
agi­
i n t o a 100 m l . of w a t e r
The oil after d i s t i l l a t i o n
gave 6.13
sealed
and the r e a c t i o n w a s
The a q u e o u s m i x t u r e w a s p o u r e d
a vacuum,
flask w a s
shaker and m o n i t o r e d
the d i e t h y l m a l o n a t e had d e c r e a s e d
stirred.
into a 5 0 - m l .
The r e a c t i o n m i x t u r e w a s
tated by m e a n s of a w r i s t - a c t i o n
malonate.
homo­
(0.188 m o l e s ) of dry, hot p o t a s ­
septum q u i c k l y .
(3% S E - 3 0 , 5' x 1/4"
shaken u n t i l
to identify
on r e ­
Actual
the above
com­
pounds.
Similarly,
the same r e a c t i o n was c o n d u c t e d
in the
sence of 1 8 - c r o w n - 6 .
A slower r e a c t i o n w a s noted and the
up, as a b o v e , y i e l d e d
4.21 g. of a m i x t u r e of d i e t h y l
and d i e t h y l m e t h y l m a l o n a t e .
Glpc
(bromocyclohexane
ab­
work
malonate
internal
44
standard,
3% S E - 3 0 ,
5' x 1/4", 9 0 ° C) showed
c o n s i s t of 46V. d i e t h y l m a l o n a t e
(1.95 g.)
the m i x t u r e
and
2.26 g.
based o n r e c o v e r e d d i e t h y l m a l o n a t e ) of d i e t h y l
18-Crown-6
Cyanogen Bromide/18-crown-6
I.
(26V.
methylmalonate.
Complexes
Complex
To a v i a l c o n t a i n i n g a p p r o x i m a t e l y
s e v e n m l . of
d i e t h y l e t h e r w a s added 1 8 - c r o w n - 6 u n t i l t h e
became difficult.
dry
solubilization
T h e n solid c r y s t a l s of c y a n o g e n
(Eastman K o d a k ) w e r e a d d e d to t h e e t h e r
bromide
s o l u t i o n and
solubi­
lized by c r u s h i n g the c r y s t a l s w i t h a s p a t u l a u n t i l a l l
solid d i s s o l v e d .
was placed
and the s o l u t i o n c o l l e c t e d .
in a v i a l and sealed u n d e r N 2
large monoclinic
The
The
solution
After a week a
crystal formed approximately
(nujol) 2160 cm
(ether, C - 0 ) ; N M R p e a k s
1
white
solution
5mm. b y
3mm.
T h e c o m p l e x had a m e l t i n g p o i n t a t 6 4 . 5 - 6 8 ° C; i n f r a r e d
sorptions
the
T h i s p r o c e d u r e w a s f o l l o w e d u n t i l fine
c r y s t a l s b e g a n to p r e c i p i t a t e from t h e s o l u t i o n .
was then filtered
to
(nitrile, C = N ) and 1 1 0 0 cm
( C D C 1 , internal TMS)
3
6 3.7
ab­
1
(crown
143
e t h e r ) ; crystal density,
c a l c . 1.529
g / m l , found
1.526
g/ml.
II.
To a vial containing
was added
f i v e m l . of c a r b o n
1 8 - c r o w n - 6 and the m i x t u r e w a s h e a t e d
18-crown-6.
tetrachloride
to
dissolve
This procedure was repeated until no more 1 8 -
crown-6 could be solubilized.
T h e n solid c y a n o g e n
bromide
(Eastman) w a s a d d e d to the h o t s o l u t i o n and d i s s o l v e d
by
45
crushing
milky
the solid w i t h a spatula until
in c o l o r .
lowed to cool
percipitated
Then the s o l u t i o n w a s heated
slowly
to room t e m p e r a t u r e .
from the s o l u t i o n .
in a v i a l .
of the
crystals
filtered
and
The d e n s i t y of the c r y s t a l s w a s m e a s u r e d
g/ml and 1.517
value.
Nice prism
in a g l o v e bag
2
in c a r b o n t e t r a c h l o r i d e and b e n z e n e .
1.514
turned
a g a i n and a l ­
The c r y s t a l s w e r e
from the c a r b o n t e t r a c h l o r i d e u n d e r N
sealed
the s o l u t i o n
g/ml compared
The v a l u e o b t a i n e d
to 1.529
g/ml,
was
calculated
The m . p . of these c r y s t a l s a g r e e d w i t h the a b o v e m . p .
complex.
Anal. Calcd.
for C
N, 5.89; Br, 3 3 . 5 7 .
1
2
H
Found;
2
4
0
6
(CNBr) *.
C,
2
3 5 . 3 1 ; H,
5.08;
C, 3 8 . 4 5 ; H, 5.81; N , 5.02;
Br,
28.39.
Malonitrile/18-Crown-6
Complex
To e i g h t m l . of dry b e n z e n e w a s added
moles)
18-crown-6
and 1.5
s o l u t i o n w a s heated
allowed
until
g.
solubilization was effected
and w a s c o l l e c t e d
rial was recrystallized
A white
from dry b e n z e n e and y i e l d e d
(CD CN,
3
glet, malononitrile)
frared
MR
absorption
(acetone-dg,
S 3.7
(nujol m u l l )
and
The m a t e ­
uniform
6 3.9
(4 H,
sin­
(24 H, s i n g l e t , c r o w n ) ;
2242 cm
i n t e r n a l TMS s t a n d a r d )
-1
at
then
complex; m . p . 1 2 7 -
i n t e r n a l TMS) at
and at
The
crystalline
by f i l t r a t i o n .
n e e d l e c r y s t a l s of m a l o n i t r i l e / 1 8 - c r o w n - 6
1 2 9 ° C; N M R p e a k s
(0.0076
(0.023 m o l e s ) m a l o n i t r i l e .
to c o o l to room t e m p e r a t u r e .
solid p r e c i p i t a t e d
2.0 g.
(nitrile, C = N ) ;
6 -70.742
in13
C
(methylene,
13
-CH -0);
0
C NMR
(acetonitirle-d-,,
i n t e r n a l TMS s t a n d a r d )
at
4 6
<S
- 1 1 2 . 7 9 0
( N I T R I L E ,
A N A L .
7 . 1 2 ;
N ,
- C = N )
C A L C U L A T E D
1 4 . 1 4 ;
0,
,
A L
C
F O R
2 4 . 2 1 .
«S
1
2
1
9 8 5
N
2 * 2
5 4 . 4 7 ;
H ,
1 4 ° 6
F O U N D ;
*
C ,
C
3
H
2
:
C
.
-CII -0)
( M E T H Y L E N E
2
5
'
4
7 . 1 4 ;
4
-
3
;
1
N ,
1
'
1 4 . 1 6 ;
2 4 . 2 3 .
0,
S U C C I N O N I T R I L E / 1 8 - C R O W N - 6
T O
E I G H T
C I N O N I T R I L E
M O L E S ) .
F E C T E D
T H E
M L .
( 0 . 0 0 2 5
T H E
A N D
O F
M O L E S )
S O L U T I O N
T H E N
S O L U T I O N
W A S
2 . 9
( 8
M U L L )
A T
6
- C H
2
,
A N
W H I T E ,
T M S )
S I N G L E T ,
2 2 2 1
C M "
- 1 1 8 . 1 2 9
1
T O
G I V E
3 . 7
6
S O L I D
( 2 4
( N I T R I L E ,
( N I T R I L E ,
C = N ) ;
C = N )
C
A N D
B A T H
1
T O
C R Y S T A L S
C ;
A T
6
E F ­
T H E N
P R E ­
A N D
O F
W A S
S U C -
N M R
S I N G L E T ,
M R
W A S
R E C R Y S T A L L I Z E D
I N F R A R E D
3
( 0 . 0 0 3 8
E F F E C T
P R E C I P I T A T E D
8 3 - 8 4 °
S U C C I N O N I T R I L E ) ;
S U C -
1 8 - C R O W N - 6
W A S
H ,
G .
T E M P E R A T U R E .
N E E D L E
M . P .
0 . 2 0 2
S O L U B I L I Z A T I O N
R O O M
M A T E R I A L
C O M P L E X ;
A T
O F
I C E - W A T E R
T H E
T O
A D D E D
U N T I L
C R Y S T A L L I N E
T E T R A C H L O R I D E
I N T E R N A L
H ,
H E A T E D
I N
C I N O N I T R I L E / 1 8 - C R O W N - 6
3
G R A M
O N E
C O O L E D
F I L T R A T I O N .
( C D C 1
A N D
C O O L
C O L L E C T E D
C A R B O N
W A S
T O
A
F R O M
B E N Z E N E
A L L O W E D
W A S
B Y
C O M P L E X
D R Y
C I P I T A T I O N .
P E A K S
C R O W N )
A N D
A B S O R P T I O N
( C D C 1
3
,
I N T E R N A L
- 7 0 . 7 1 3
6
( N U J O L
T M S )
( M E T H Y L E N E ,
- 0 ) .
A N A L .
C A L C U L A T E D
F O R
C ,
1 2
7 . 6 0 ;
O ,
I
- 7 0 .
N ,
1 3 . 2 8 .
2 2 . 6 2 ;
O ,
1 3 . 2 0 .
O
A
1 4
F O U N D :
( C . H . N
c
6
C ,
4
4
5 7 . 0 6 ;
N
2
)
N
:
C ,
5 6 . 5 5 ;
H ,
N ,
2 1 . 9 8 ;
2
H ,
7 . 6 8 ;
47
CHAPTER
RESULTS AND
III
DISCUSSIONS
A s n o t e d e a r l i e r , t h e m a i n u s e of p o t a s s i u m
in o r g a n i c c h e m i s t r y h a s b e e n a s a f l u o r i n a t i n g
fluoride
agent, al­
t h o u g h r e p o r t s i n d i c a t e the a b i l i t y of f l u o r i d e i o n s to
act
22-45
as a base.
The major problem
in e i t h e r
in u s i n g p o t a s s i u m
system h a s b e e n t h e i n s o l u b i l i t y o f the m a t e r i a l
122
in o r g a n i c
markable
fluoride
solvents.
L i o t t a and H a r r i s
s u c c e s s in s o l u b i l i z i n g p o t a s s i u m
and n o n p o l a r , a p r o t i c
solvents
123
'
h a v e had r e ­
fluoride
in p o l a r
(acetonitrile and b e n z e n e )
with
the aid of 1 8 - c r o w n - 6 ; the r e s u l t i n g r e a g e n t w a s e f f e c t i v e
fluorination.
T h e c a p a b i l i t i e s o f t h e "naked" f l u o r i d e
to b e h a v e a s a b a s e w a s i n v e s t i g a t e d
in
ion
in t h e p r e s e n t w o r k .
S e l e c t e d M i c h a e l , K n o e v e n a g e l , and a l k y l a t i o n r e a c t i o n s
were
conducted
a t r o o m t e m p e r a t u r e w i t h the f o l l o w i n g g e n e r a l
clusion:
the r e a c t i o n s u s i n g
"naked" f l u o r i d e i o n s
con­
required
s h o r t e r r e a c t i o n s t i m e s and p r o d u c e d b e t t e r , o r a t l e a s t
a l e n t , y i e l d s of p r o d u c t s t h a n t h e r e a c t i o n s w i t h no
equiv­
18-crown-6.
A l l the r e a c t i o n s w e r e c a r r i e d o u t in a c e t o n i t r i l e ,
e x c e p t the K n o e v e n a g e l r e a c t i o n s w h i c h w e r e c a r r i e d o u t
benzene.
and
used
These solvents were used
i n e r t to the f l u o r i d e a n i o n .
since t h e y a r e l o w
122
Harris
boiling
The 18-crown-6 ether
in a l l c a s e s o n l y in c a t a l y t i c q u a n t i t i e s .
in
Liotta
was
and
123
'
measured
the s o l u b i l i t i e s o f p o t a s s i u m
fluoride
4 8
i n
t h o s e
s u m i n g
s o l v e n t s .
a
l i n e a r
c r o w n
a n d
r a n g e
o f
i n
t h e
T h e i r
r e l a t i o n s h i p
u s e d
i n
t h e
- 3
2
i n
x
o f
a r e
t a b u l a t e d
b e t w e e n
c o n c e n t r a t i o n
c o n c e n t r a t i o n s
s o l u t i o n ,
d a t a
o f
t h e
p r e s e n t
T a b l e
1 .
c o n c e n t r a t i o n
p o t a s s i u m
p o t a s s i u m
i n
f l u o r i d e ,
f l u o r i d e
o r
r e a c t i o n s
w a s
a n d
o f
t h e n
t h e
f l u o r i d e
M
t o
5 . 6
x
i o n
a p p r o x i m a t e l y
- 3
1 0
A s ­
- 3
1 0
M
i n
a c e t o n i t r i l e
K F
i n
P r e s e n c e
8 . 2
x
1 0
1 8 - C r o w n - 6
a t
M
b e n z e n e .
T a b l e
1 .
S o l u b i l i t y
o f
S o l v e n t
( 1 8 - C r o w n - 6 ) ,
o f
2 5 °
C
(KF)T~M
M
- 4
A c e t o n i t r i l e
3
x
1 0
3 . 5
x
1 0
5 . 2
x
1 0
1 . 4
x
1 0
0
- 3
0 . 1 6
- 2
B e n z e n e
1 . 0 1
0 . 3 4
M i c h a e l
T h e
l o n i t r i l e
a c e t a t e
M i c h a e l
a n d
a n d
s u b s t r a t e
d i e t h y l
m o l a r
f r o m
o f
r e a c t i o n s
t h e
o n e
E t h y l
l o n i t r i l e
a n d
p r o d u c t s ,
Y " "
t o
s u b s t r a t e s
m a l o n a t e
a s
r e a c t a n t s .
( r e f e r r e d
( 1 : 1 )
c
a
r
o f
i n
t o
t o
w i t h
a s
e a c h
g e n e r a t e
t h e
c y a n o ­
R / S
t o
r a t i o )
T h e
w a s
r e s u l t s
2 .
r e s p e c t i v e l y ,
H o w e v e r ,
a c r y ­
r e a c t a n t
( 1 : 2 ) .
s u b s t r a t e
t h e
k e t h o x y - y - c y a n o p i m e l o n i t r i l e
1 8 - c r o w n - 6 .
u s i n g
e t h y l
T h e
t w o
T a b l e
o u t
w i t h
f u r t h e r
o n e
r e a c t e d
a c r y l a t e ,
c a r b e t h o x y - y - c y a n o p i m e l a t e ,
a b s e n c e
t o
t o
t a b u l a t e d
c y a n o a c e t a t e
e t h y l
c a r r i e d
a s
o n e
a r e
w e r e
a c r y l a t e
r a t i o
v a r i e d
C o n d e n s a t i o n s
c o n d e n s a t i o n s
e t h y l
- 2
d i s u b s t i t u t e d
a n d
i n
r e a c t i o n
a c r y ­
t h e
d i e t h y l
p r e s e n c e
t i m e s
w e r e
y ~
a n d
d e -
Table 2.
Michael Condensations initiated by Potassium Fluoride in the Presence and Absence of 18-Crown-6
Product
Substrate
Cone.. (M)
Reactant
Cone. (M)
1..0
1,.0
2,.0
2,.0
2,.0
1.1
1.1
1.1
1.1
1.1
0..098
0
0.,098
0
0..098
ambient
Y,Y~dicarbethoxypimelonitrile
1..0
2,.0
1.1
1.1
0.,098
0.,098
ambient
ambient
ethyl a-carbethoxyY-cyanobutyrate
2..0
1.1
0
25°
diethyl Y~carbethoxyY-cyanopimelate
1,.0
2..0
2..0
1.1
1.1
1.1
0,.098
0,.098
0
diethyl a-carbethoxyglutarate
1,.0
2..0
1.1
1.1
diethyl
Y,Y~dicarbethoxypimelate
1..0
2..0
1.1
1.1
Y-carbethoxy-YcyanopimeIon i t irle
a :
b :
c :
d :
d*:
e :
Crown
Cone. (M)
Temperature
°C
e
Time
(hr)
% Yield
isolated
0.17
4
0.25
A3
0.25
86
80
83
84
90
a
a
a
a
a
73
82
b
b
121
84
b
ambient
ambient
ambient
3
0.17
13
64
75
67
c
c
c
0..098
0
ambient
25°
3
96
62
36
d*
d
0,.098
0..098
ambient
ambient
3
3
8
58
d*
d
ambient
25°
ambient
4
3.5
acrylonitrile as substrate with ethyl cyanoacetate as reactant
acrylonitrile as substrate with diethyl malonate as reactant
ethyl acrylate as substrate with ethyl cyanoacetate as reactant
ethyl acrylate as substrate with diethyl malonate as reactant
the same reaction
ambient refers to a temperature increase above room temperature for a period of time during
the reaction with eventual return to room temperature
to
50
p e n d e n t on the s u b s t r a t e
18-crown-6.
concentrations
Ethyl cyanoacetate
in the p r e s e n c e
reacted w i t h e q u a l facility w i t h
late w h e n
of
reaction
acrylonitrile
the R/S r a t i o w a s one to one
18-crown-6
the above r e a c t i o n s
times.
disubstituted
Even in dry
products, Y~
c a r
and the p r e s e n c e
of
of
18-crown-6
and e t h y l
(1:1).
In the
absence
all had c o n s i d e r a b l e
acetonitrile with
acry­
longer
18-crown-6
the
bethoxy-Y-cyanopimelonitrile,
was
isolated.
Aoyama
37
ethyl acrylate
fluoride
and K a n b e
ducts were obtained
The c o n d i t i o n s
synthetic
in e t h a n o l w i t h
in low y i e l d s of 3 2 % and
for the r e a c t i o n s
(R/S r a t i o
at 4 0 - 5 0 ° C for a c r y l o n i t r i l e
and
substituted
ethyl cyanoacetate
routes
potassium
39%,
1:1)
are b e t t e r
pro­
respectively.
required
and r e f l u x i n g
for e t h y l a c r y l a t e .
a c e t o n i t r i l e , as s o l v e n t ,
products
with
In each c a s e , the d i s u b s t i t u t e d
for three and o n e - h a l f h o u r s
18-crown-6
reacted
and a c r y l o n i t r i l e
as the b a s e .
seven h o u r s
39
However,
the y i e l d s
and compare
ethanol
with
of the d i ­
favorable
to
other
to these
products.
obtained
Y"Carbethoxy-Y-cyanopimelonitnle
129
Bruson
in a 9 8 % c r u d e y i e l d
anoacetate
C.
acrylonitrile
and e t h y l
(R/S r a t i o 2:1) in d i o x a n e w i t h T r i t o n B at
12 8
Similarly, Tenniswood
cyanopimelate
in an isolated
anoacetate with
1:1)
from r e a c t i n g
3-cyanoethyl
in e t h a n o l w i t h
obtained
86% y i e l d
diethyl
30-35°
Y^carbethoxy-y
from r e a c t i n g
toluene-p-sulphonate
s o d i u m at room t e m p e r a t u r e
Diethyl malonate
cy­
ethyl
(R/S
for
reacted w i t h each s u b s t r a t e ,
-
cy­
ratio
18 h o u r s .
aery-
51
lonitrile and e t h y l c y a n o a c e t a t e .
p r e s e n c e of
With acrylonitrile
1 8 - c r o w n - 6 , d i e t h y l m a l o n a t e yielded
tuted p r o d u c t y, y d i c a r b e t h o x y p i m e l o n i t r i l e
w h e r e the R/S r a t i o s w e r e one to one
(1:2).
(1:2),
disubsti­
in b o t h
cases
and the R/S
only the m o n s u b s t i t u t e d
a-carbethoxy-y-cyanobutyrate
w a s found.
product,
With ethyl
ratio
ethyl
acrylate
in the p r e s e n c e of 1 8 - c r o w n - 6 , d i e t h y l m a l o n a t e y i e l d e d
the m o n o and d i s u b s t i t u t e d
(1:1) the
product, diethyl a-carbethoxygluterate,
ydicarbethoxypimelate.
w a s isolated
as
Y, y d i c a r b e t h o x y g l u t e r a t e
crown-6 was present
the only p r o d u c t
was isolated.
isolated w a s d i e t h y l
for the r e a c t i o n s w i t h
actions containing
product,
However,
no
the
pro­
ratio
diethyl
if n o 1 8 -
and the R/S r a t i o w a s one to two
In each c a s e , a g a i n , the r e a c t i o n
shorter
W h e n the R/S
(1:2) only the d i s u b s t i t u t e d
ratio.
monosubstituted
m a j o r p r o d u c t with the m i n o r p r o d u c t , the d i s u b s t i t u t e d
w a s one to two
both
p r o d u c t s d e p e n d i n g on the R/S
W h e n the R/S r a t i o was one to one
d u c t , d i e t h y l y,
the
(1:1) and one to two
Yet, w h e n n o 18-crown-6 w a s p r e s e n t
w a s one to two
the
in
(1:2)
a-carbethoxygluterate.
times w e r e
considerably
18-crown-6 p r e s e n t
than the
re­
18-crown-6.
3 8 39
Kanbe
'
and a c r y l o n i t r i l e
base.
ratio
Kanbe
reacted d i e t h y l m a l o n a t e w i t h e t h y l
in e t h a n o l w i t h p o t a s s i u m
found d i e t h y l m a l o n a t e
1:1) y i e l d e d
fluxing
f l u o r i d e as
and e t h y l a c r y l a t e
only the m o n o s u b s t i t u t e d
a-carbethoxygluterate
acrylate
product,
the
(R/S
diethyl
w i t h an isolated y i e l d of 55% after
for f o u r t e e n h o u r s .
On the other h a n d , K a n b e
re­
found
52
diethyl malonate and acrylonitrile (R/S ratio 1:2)
only the disubstituted product, diethyl y, y-dicarbeth
nitrile with an isolated yield of 68% and required
seven hours at 50-60° C. However, the use of
conjunction with 18-crown-6 gave equivalent yields, as
above, with less stringent conditions. In fact, t
compare favorable to yields obtained by other synthet
Tenniswood obtained both ethyl a-carbethoxy-y-cyanopimelonitrile and y, y-dicarbethoxypimelonitrile in isolate
yields of 33% and 34%, respectively from reacting
malonate and $-cyanoethyl toluene-p-sulphonate (R/S ratio
in refluxing ethanol for eight hours with sodium.
R/S ratio was one to two (1:2), only y, y-dica
129
lonitrile was isolated in 80% yield. Bruson isolate
y-dicarbethoxypimelonitrile in 82% yield from the reactio
diethyl malonate and acrylonitrile (R/S ratio 1:2)
with Triton B as the base at room temperature fo
Bankertobtained diethyl a-carbethoxyglutarate and diethy
y, y-dicarbethoxypimelate in 21 and 18% isolated yie
spectively by reacting diethyl malonate and beta-propiol
(R/S ratio 1:1) in ethanol at 30° with sodium.
Attempted Michael condensation of cyclohexanone with
ethyl acrylate in the presence of 18-crown-6 yielded
small amounts of the mono and disubstituted products,
2-oxocylohexanepropionate and diethyl 2-oxocyclohexanebis
(dipropionate), respectively, even at reflux conditions.
12 8
641
r
low y i e l d s and
long r e a c t i o n
a b i l i t y of the f l u o r i d e
ing to the
in r e a c t i o n times of the M i c h a e l
two closely
pair a s s o c i a t i o n .
c e n t r a t i o n of p o t a s s i u m
centration
of
"naked"
condensa­
related p r o c e s s e s , s o l u b i l i t y
fluoride
lead­
can be e x p l a i n e d
In the p r e s e n c e of 1 8 - c r o w n - 6
lity of p o t a s s i u m
in­
enolate.
tions caused by the p r e s e n c e of 1 8 - c r o w n - 6
considering
to the
ions to remove the alpha p r o t o n
f o r m a t i o n of the
The decrease
time may be related
>3
increases.
fluoride
fluoride
the
and
ion-
solubi­
W i t h the i n c r e a s e d
con­
in s o l u t i o n , an increased
ion w a s e x p e c t e d
by
since
con­
18-crown-
102—119
6 has been
shown to i n c r e a s e
With a reduction
pected
ion-pair
in s o l v a t i o n
to show an increased
the
"naked" f l u o r i d e
reactivity
c r e a s e in the M i c h a e l d o n o r c a r b a n i o n
s h i f t i n g of the e q u i l i b r i u m s
w i t h shorter
dissocation.
should
lead to an
concentration
to the M i c h a e l adduct
r e a c t i o n times w h i c h are
ion w a s
and a
products
conducted Michael
condensations with potassium
fluoride
bility
in e t h a n o l w a s d e t e r m i n e d
fluoride
in­
noticed.
A s noted e a r l i e r , Kanbe and A o y a m a
of p o t a s s i u m
ex­
in a l c o h o l .
The
solu­
by
147
Germuth.
potassium
The d a t a is t a b u l a t e d
fluoride
temperatures
However,
than
is m o r e s o l u b l e
in T a b l e
3.
As noted,
in e t h a n o l at
the
corresponding
in a c e t o n i t r i l e even w i t h 1 8 - c r o w n - 6
present.
the r e a c t i o n c o n d i t i o n s used by Kanbe and A o y a m a
h a r s h e r and r e q u i r e d
longer t i m e s .
T h e longer t i m e s are
d o u b t l y d u e to s o l v a t i o n e f f e c t s , n a m e l y h y d r o g e n
and the d e c r e a s e of the s o l u b i l i t y of p o t a s s i u m
were
un148
bonding,
fluoride
at
54
T a b l e 3.
S o l u b i l i t y of KF in A n h y d r o u s E t h a n o l
per m o l e of e t h a n o l )
Temperature
salt
KF
20
0.00084
( 1.4x10
30
0.00076
(1.3xl0"
2
M)
40
0.00054
(9.0xl0"
3
M)
45
0.00039
50
0.00018
55
0.00008
higher temperatures.
and e t h o x i d e
(moles of
The e q u i l i b r i u m
M)
(10) b e t w e e n
in the p r e s e n c e of p o t a s s i u m
ethanol
fluoride appears
to
be
F~
+
EtOH
j
v
EtO~
+
HF
(10)
41
negligible.
Yasuda
found p r i m a r y and
acted e a s i l y w i t h a c r y l o n i t r i l e
in the p r e s e n c e of
c a t a l y s t s to form the c o r r e s p o n d i n g
ever, when ethanol was used
secondary alcohols
trile w a s o b t a i n e d .
t i v e s in their
in the p r e s e n c e of p o t a s s i u m
Kanbe and A o y a m a
studies.
alkaline
alkoxypropionitriles
o r i d e w i t h a c r y l o n i t r i l e , n e g l i g i b l e or no
re­
How­
flu­
ethoxypropropioni-
found no a l k o x y
deriva­
55
Knoevenagel
Condensations
The K n o e v e n a g e l c o n d e n s a t i o n s w e r e c a r r i e d out
benzaldehyde
and in one case c y c l o h e x a n o n e
ethylcyanoacetate,
actants.
as s u b s t r a t e s
d i e t h y l m a l o n a t e , and m a l o n o n i t r i l e
The R/S r a t i o w a s m a i n t a i n e d
at one to one
The r e s u l t s of these r e a c t i o n s are t a b u l a t e d
Examination
of T a b l e
4 indicated
out in the p r e s e n c e of 18-crown-6
case of d i e t h y l m a l o n a t e
In the
The low yield
only
any p r o d u c t e v e n w i t h
and h a r s h e r r e a c t i o n
for d i e t h y l m a l o n a t e may be related
,)
4.
have s h o r t e r t i m e s .
fluxing b e n z e n e .
n
in T a b l e
carried
18-crown-6 y i e l d e d
(t
as r e -
(1:1).
condensing with benzaldehyde,
c a r b o n y l or a slower s u b s e q u e n t
with
the r e a c t i o n s
the r e a c t i o n w i t h
The half-times
using
conditions
to slow attack on
the
step, the d e h y d r a t i o n
for the c o n d e n s a t i o n s w i t h
re-
step.
malononitrile
1/2
and e t h y l c y a n o a c e t a t e
crown-6
as r e a c t a n t s
in the p r e s e n c e
of 1 8 -
are all of the same o r d e r , o n e - h a l f m i n u t e .
v a l u e of h a l f - t i m e
for e t h y l c y a n o a c e t a t e
w i t h the h a l f - t i m e
(1.5 m i n . )
cyanoacetate
oride under
for the c o n d e n s a t i o n
and b e n z a l d e h y d e w i t h
a c e t i c acid as c a t a l y s t
compares
e-aminocaproic
in r e f l u x i n g b e n z e n e .
This
favorable
of
ethyl
acid
and
Potassium
s i m i l a r c o n d i t i o n s , as a b o v e , y i e l d e d
flu­
half-times
for the same r e a c t i o n of
10 m i n u t e s w i t h a c e t i c acid p r e s e n t
149
and 16 m i n u t e s w i t h no a c e t i c acid.
The expected product
form the c o n d e n s a t i o n of e t h y l c y a n o a c e t a t e and b e n z a l d e h y d e
w a s the trans p r o d u c t w i t h r e s p e c t
150
groups.•
L D U
to the a r y l and
carbethoxy
Table
4.
Knoevenagel
Absence
Product
Condensations
of
initiated
by
Potassium
Fluoride
in
the
Presence
Substrate
Reactant
Crown
Cone.
Cone.
Cone.
(M)
(M)
benzylidene-
Temperature
°C
(M)
0.2
ambient
0
25°
malononitrile
Time
(hr)
0.17
16.8
^1/2*
(min.)
%
Y
i
e
l d
isolated
0.5
77
9.1
84
cyclohexylidene-
2
0.2
ambient
0.17
0.5
71
malononitrile
2
0
ambient
1.0
7.5
68
0.2
ambient
0.2
0.5
0
25°
144
46
reflux
96
reflux
96
33
0
ethyl
benzylidene-
81
cyanoacetate
ethyl
0.2
0
benzylmalonate
a
:
benzaldehyde
b
:
cyclohexanone
c
:
benzaldehyde
as
substrate
with
ethyl
d
:
benzaldehyde
as
substrate
with
diethyl
*
:
time
for
and
18-Crown-6
as
as
i n i t i a l
substrate
substrate
base
peak
with malononitrile
as
with malononitrile
area t o
reactant
as
reactant
cyanoacetate
malonate
decrease
by
as
50%
as
reactant
reactant
57
Rand
conducted
similar r e a c t i o n s using p o t a s s i u m
oride as the b a s i c c a t a l y s t
tions r e q u i r e d
heating
four h o u r s e x c e p t
at 2 5 °
C.
in b e n z e n e .
H o w e v e r , the
condensed with
The r e a c t i o n of d i e t h y l m a l o n a t e w i t h
times for the r e a c t i o n s
benzaldehyde
The y i e l d s , t h o u g h , w h e n
comparable
18-crown-6
were
was
18-crown-6 w a s p r e s e n t
to the y e i l d s o b t a i n e d by Rand,
s y n t h e t i c routes except
products.
carried out by Rand
longer than the r a c t i o n times r e q u i r e d w h e n
present.
twenty-
benzaldehyde
at 6 0 ° C for t w e n t y - f o u r h o u r s y i e l d e d no i s o l a t e d
The r e a c t i o n
reac­
at 6 0 % C for p e r i o d s of six to
for m a l o n o n i t r i l e
flu­
are
as w e l l a s , by
for the d i e t h y l m a l o n a t e
other
condensation.
30
Aoyama
yield
obtained
from c o n d e n s i n g e t h y l c y a n o a c e t a t e
(R/S r a t i o 1:1)
sium
ethyl b e n z y l i d e n e c y a n o a c e t a t e
in r e f l u x i n g
f l u o r i d e as c a t a l y s t .
ethanol
Pratt
ing b e n z y l i d e n e m a l o n o n i t r i l e ,
ethyl
x
and
Pratt carried
r a t i o of one to one
has obtained
nonitrile
Cope
similarly
the i n c r e a s e
and
89%, re­
obtained
piperidine
from
cyclohexylidenemalo-
(R/S r a t i o 1:1) w i t h p i p e r i d i n e
and
cy­
as the b a s e .
in the K n o e v e n a g e l
18-crown-6 w a s u n d o u b t l y
in the s o l u b i l i t y
R/S
removing water
from c o n d e n s i n g m a l o n o n i t r i l e
in the p r e s e n c e of
follow­
out these r e a c t i o n s w i t h an
The s h o r t e r r e a c t i o n times noted
actions
72%,
(1:1) in r e f l u x i n g b e n z e n e w i t h
in 8 0 % y i e l d
clohexanone
the
benzylidenecyanoacetate,
and c a p r o i c acid p r e s e n t and c o n t i n u a l l y
] 39
the system.
benzaldehyde
for one h o u r w i t h p o t a s -
and e t h y l b e n z a l m a l o n a t e w i t h y i e l d s of 74%,
spectively.
75%
in
of p o t a s s i u m
fluoride
re­
related
and
ion
to
58
pair d i s s o c i a t i o n .
potassium
"naked"
With an increase
in the c o n c e n t r a t i o n
fluoride in s o l u t i o n , an increased
fluoride ions w a s e x p e c t e d
ion pair d i s s o c i a t i o n .
concentration
since
c o n c e n t r a t i o n of
18-crown-6
This i n c r e a s e in "naked"
can be expected
to i n c r e a s e the
should
increases
fluoride ion
concentration
of the c a r b a n i o n of the active m e t h y l e n e c o m p o u n d .
c r e a s e of the c a r b a n i o n c o n c e n t r a t i o n
of
This i n ­
shift the e q u i l i ­
b r i u m toward a d d i t i o n across the c a r b o n y l followed by d e h y d r a ­
tion to the d o u b l e bond
adduct.
Alkylations
The a l k y l a t i o n s w e r e carried out in a c e t o n i t r i l e
using
b e n z y l b r o m i d e , b e n z y l c h l o r i d e , and m e t h y l iodide as s u b ­
strates w i t h d i e t h y l m a l o n a t e
was maintained
in T a b l e
at o n e to one
as the r e a c t a n t .
(1:1).
T h e R/S r a t i o
T h e r e s u l t s are t a b u l a t e d
5.
E x a m i n a t i o n of T a b l e
5 reveals
ried out in the p r e s e n c e of 1 8 - c r o w n - 6
the r e a c t i o n s w i t h o u t
18-crown-6.
that the r e a c t i o n s
car­
has b e t t e r y i e l d s
than
The r e a c t i o n s
involving
the b e n z y l h a l i d e s y i e l d e d no isolated p r o d u c t s w h e n
w a s not p r e s e n t .
The h a l f - t i m e s
tions show the b r o m i d e
b a n i o n m o r e readily
o r d e r of leaving
(t.^^^) f °
r
these two r e a c ­
w a s d i s p l a c e d by d i e t h y l m a l o n a t e
than the c h l o r i d e .
group abilities.
the r e a c t i o n .
car­
T h i s w a s the e x p e c t e d
H o w e v e r , the d i s p l a c e m e n t
of iodide from m e t h y l iodide by the d i e t h y l m a l o n a t e
was extremely
18-crown-6
carbanion
slow as noted by the length of time r e q u i r e d
for
T h e r e is n o e x p e r i m e n t a l e v i d e n c e a v a i l a b l e , as
Table 5.
Alkylations Iniated by Potassium Fluoride in the Presence and Absence of 18-Crown-6
Product
Substrate
Cone. (M)
Reactant
Cone. (M)
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
0.12
0
0.12
0
25
25
25
25
41
41
186
186
diethyl
dibenzylmalonate
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
0.12
0
0.12
0
25
25
25
25
41
41
186
186
diethyl
methylmalonate
2.5
2.5
2.6
2.6
0.26
0
25
25
1392
1392
diethyl
benzylmalonate
a
b
c
Crown
Cone. (M)
Temperature
°C
Time
(hr)
benzyl bromide as substrate and diethyl malonate as reactant
benzyl chloride as substrate and diethyl malonate as reactant
methyl iodide as substrate and diethyl malonate as reactant
t
*
(min.)
% Yield
isolated
7.4
63
0
56
0
1 / 2
49.5
7.4
49.5
12
0
10
0
53
26
60
yet, to e x p l a i n
this a n o m a l y .
halide, monoalkylated
in similar y i e l d s .
monoalkylated
In both cases w i t h the
and d i a l k y l a t e d
products were
In the case of m e t h y l
benzyl
isolated
i o d i d e , only
the
p r o d u c t w a s isolated w i t h no e v i d e n c e of d i a l ­
kylated product.
p r o d u c t s compare
O v e r a l l , t h o u g h , the y i e l d s of the
favorably
to other s y n t h e t i c
alkylated
routes.
141
Sen
chloride
found d i e t h y l m a l o n a t e reacted w i t h
(R/S r a t i o n
sium c a r b o n a t e
product
1:1)
in dry e t h a n o l w i t h a n h y d r o u s
and p o t a s s i u m
isolated
to r e f l u x
c a r b o n a t e used
f l u o r i d e as the b a s e .
potas­
The
only
from the r e a c t i o n w a s the m o n o s u b s t i t u t e d
duct, diethyl benzylmalonate
heated
benzyl
(64%).
for e i g h t h o u r s .
The reaction mixture
The need
in the r e a c t i o n w a s not m a d e
for the
pro­
was
potassium
clear.
152
Leucks
isolated d i e t h y l b e n z y l m a l o n a t e
diethyl dibenzylmalonate
and b e n z y l c h l o r i d e
presence
of sodium.
benzylmalonate
(12%) from r e a c t i n g d i e t h y l
(R/S r a t i o 2:1)
Similarly, Marvel
in r e f l u x i n g
malonate
isolated
in
a b s o l u t e e t h a n o l w i t h sodium.
diethyl malonate
and m e t h y l iodide
absolute ethanol with
18-Crown-6
(R/S r a t i o
. .
154
Olivier
(80%) and some d i e t h y l
the
diethyl
(51-57%) and some d i e t h y l d i b e n z y l m a l o n a t e
diethyl methylmalonate
by r e a c t i n g
and
in a b s o l u t e e t h a n o l
153
r e a c t i n g d i e t h y l m a l o n a t e and b e n z y l c h l o r i d e
in r e f l u x i n g
(85%)
by
1:1)
isolated
dimethylmalonate
(R/S r a t i o
1:1)
sodium.
Complexes
In the c o u r s e of this r e s e a r c h
three n o v e l
non-metallic
51
18-crown-6
complexes were
plexes were
formed with
succinonitrile.
isolated,
see T a b l e
The c y a n o g e n b r o m i d e complex
for a two to one c o m p l e x
18-crown-6 m o l a r r a t i o ) .
trile and s u c c i n o n i t r i l e
point
complexes
the
to
calculated
(nitrile to 18-crown-6
point
bro­
molar
melting
for each
constituent
complexes.
Single c r y s t a l x-ray
analysis
1 8 - c r o w n - 6 has shown the c o m p l e x
as
as
for the m a l o n i -
Each c o m p l e x , h o w e v e r , did h a v e a h i g h e r
composing
decom­
(cyanogen b r o m i d e
agreed w i t h the
than the c o r r e s p o n d i n g m e l t i n g
complex
slowly
and
low n i t r o g e n and
The analytical data
for a two to one complex
ratio).
com­
the loss of c y a n o g e n b r o m i d e ,
noted b y the a n a l y t i c a l d a t a indicating
values
Those
cyanogen b r o m i d e , m a l o n o n i t r i l e ,
posed out of s o l u t i o n w i t h
mide content
6.
depicted
in F i g u r e s
of the c y a n o g e n
to d e f i n i t e l y
1 and
2.
be a two to one
F r o m the x-ray
t u r e , the c y a n o g e n b r o m i d e m o l e c u l e s w e r e
above and b e l o w the 18-crown-6
bromide/
found to be
struc­
located
ring w h i c h w a s p l a n a r .
The
c y a n o g e n b r o m i d e m o l e c u l e s w e r e o r i e n t e d w i t h the b r o m i d e m o i ­
ety aligned
toward
the center of the 18-crown-6
bromide moiety was directly
crown-6
inserted
ring u n l i k e the c o m p l e x e s
toluene-diazonium
ring.
in the h o l e of the 1 8 1
formed by C r a m ^
tetrafluoroborate
Neither
and
1
18-crown-6.
with
p-
Cram
+
postulated
the c o m p l e x e s
g r o u p into the hole of
involved
i n s e r t i o n of the linear
18-crown-6 based on PMR
Differential thermal analysis
metric analysis
(TGA)
w a s carried
(DTA) and
out on the
-N=N
shifts.
thermogravimalononitrile
Table 6.
Elemental Analysis of 18-Crown-6 Complexes
Complex
Complex Formula
Cyanogen bromide
C H 0 (CNBr)
Malononitrile
C
12 24°6 3 2 2 2
Succinonitrile
C
l2 24°6 4V2 2
a
b
:
:
calculated
experimental
l 2
2 g
H
6
( C
H
( C
H
N
2
)
)
MP(C°)
%C
Elemental Analysis
%H
%0
%N
%Br
64. 5~
68.0
35.61
38.45
5.08
5.81
5.89
5.02
20.15
22.33
33.57
28.39
127.0129.0
54.43
54.47
7.12
7.14
14.14
14.16
24.21
24.23
-
56.55
57.06
7.60
7.68
22.62
21.98
13.20
13.28
-
8384
Figure
1.
Overview
Oxygen
:
of
Cyanogen
Bromide/18-Crown-6
Compl
Figure
2.
Sideview
Oxygen
:
of
Cyanogen
Bromide/18-Crown-6
Complex
6 5
and s u c c i n o n i t r i l e
or e x o t h e r m i c
complexes.
endothermic
t r a n s i t i o n s w e r e found b e f o r e the e n d o t h e r m a s ­
sociated with melting.
weight
In both cases no
The D T A / T G A d a t a s h o w e d
negligible
losses over the t e m p e r a t u r e r a n g e to m e l t i n g .
The
t e m p e r a t u r e w h e r e m e l t i n g o c c u r r e d , o b t a i n e d by DTA for
malonitrile
and s u c c i n o n i t r i l e
complexes was
respectively, agreeing with capillary
1 3 0 ° C and 8 7 ° C ,
tube m e l t i n g p o i n t s .
T h e n i t r i l e a b s o r p t i o n in the i n f r a r e d
2250 c m
- 1
the
region
2200-
showed a shift to lower v a l u e s w h e n the n i t r i l e s w e r e
complexed.
Malononitrile
tion and s u c c i n o n i t r i l e
on c o m p l e x a t i o n .
shifted
shifted
from 2 2 5 1 c m
- 1
from 2226 c m
Such shifts i n d i c a t e
- 1
on
complexa­
to 2 2 2 1
some w e a k e n i n g
cm
- 1
in bond
s t r e n g t h of the n i t r i l e t r i p l e b o n d , a l t h o u g h the s h i f t s
are
1 o
small.
S m a l l s h i f t s w e r e a l s o noted in the
complexes
compared
for the 1 8 - c r o w n - 6
C-NMR
the
al­
for the c o m p l e x e s .
H o w e v e r , t h e s e c o m p l e x e s can be r e c r y s t a l l i z e d .
a s t r o n g a f f i n i t y b e t w e e n the 1 8 - c r o w n - 6
solvents.
The
obtained.
No bonding scheme has been established
in n o n - p o l a r
when
of the c o m p l e x e s .
some d e g r e e of a s s o c i a t i o n in s o l u t i o n
though no quantitive results were
tionality
for
c a r b o n s and n i t r i l e c a r b o n
to the i n d i v i d u a l c o n s t i t u e n t s
shifts i n d i c a t e d
X J
This
indicates
and the n i t r i l e
func­
66
CHAPTER
IV
CONCLUSIONS
When potassium
fluoride w a s s o l u b i l i z e d
in the p o l a r and n o n p o l a r a p p r o t i c
b e n z e n e , the
"naked"
fluoride
by
18-crown-6
solvents, acetonitrile
ions p r o v e d
to be e f f e c t i v e
a b a s e c a p a b l e of c a t a l y z i n g M i c h a e l , K n o e v e n a g e l , and
tion r e a c t i o n s .
quantities.
The
18-crown-6 w a s p r e s e n t only
The r e a c t i o n times
a t w o to one m o l a r complex w i t h
C and
8 3 - 8 4 ° C,
18-
to the
yields
methods.
Cyanogen bromide, malononitrile,
and s u c c i n o n i t r i l e
alkyla-
18-crown-6 w a s not p r e ­
The y i e l d s of p r o d u c t s w e r e c o m p a r a b l e
o b t a i n e d by o t h e r s t a n d a r d
as
catalytic
for the r e a c t i o n s w i t h
c r o w n - 6 p r e s e n t w e r e s h o r t e r than w h e n
sent.
in
and
and s u c c i n o n i t r i l e
18-crown-6.
The
c o m p l e x e s w e r e stable m e l t i n g
respectively.
form
malononitrile
at
127-129°
67
CHAPTER V
RECOMMENDATIONS
Further
base
in the
field of w e a k - b a s e - p r o m o t e d
interesting.
aprotic
studies in the use of the fluoride
In a s s o c i a t i o n w i t h
solvents
should
be
anion as a
reactions
should
these s t u d i e s , other
studied as p o s s i b l e
are DMF,
D M S O , or HMPA.
18-crown-6 m a y
the fluoride
X-ray
solubility
sideration
plexes with
and d e c r e a s e r e a c t i o n
crystallography
crown-6/nitrile
vide insight
These s o l v e n t s w i t h
complexes
into the r e a s o n
should be g i v e n
to attempts
the h a l i d e d e r i v a t i v e s
crystallographic
analysis
fails
time.
on the 1 8 and p r o ­
formation.
at forming the
of the n i t r i l e s
for the
increase
their s t r u c t u r e
for such c o m p l e x
Such
N-methylpyrrolidine,
should be c o n d u c t e d
to d e t e r m i n e
polar
solvents.
s o l v e n t s w h i c h w o u l d be of interest
prove
light atom
if
Con­
com­
x-ray
complexes.
68
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