Steric effects on o-(N,N-disubstitutedamino)-thiophenols [pt. I] Synthesis of
1,1-dimethyl-2,3-dimethylenecyclopropane from delta-3-carene [pt. II]
by Steven Wayne Miller
A thesis submitted to the Graduate Faculty in partial fulfillment of the Requirements for the degree of
DOCTOR OF PHILOSOPHY in Chemistry
Montana State University
© Copyright by Steven Wayne Miller (1972)
Abstract:
The product obtained from the alkaline hydrolysis of the quaternary salt,
2-methyl-3-ethylbenzothiazolium iodide, was determined to have the structure shown below. This
product, o-(N-ethyl-N- acetylamino)-thiophenol, gave rise to a complex nmr spectrum. The methylene
protons of the ethyl proup appeared to be nonequivalent giving rise to two sets of equal multiplets. If
the methylene protons were equivalent, then they should give a quartet. Because of this
nonequivalence, several related compounds, with differing steric interactions, were prepared and from
these compounds the steric requirements for restricted rotation around the aryl to nitrogen bond were
determined.
The nmr spectrum, uv spectrum and the mass spectrum of the product of the pyrolysis of
l,l-dimethyl-2,3-bis-(dimethylamino-methyl)-cyclopropane dimethohydroxide indicated that
1,1-dimethyl-2,3-dimethylenecyclopropane had been prepared. The dimethohydr oxide was
synthesized from delta-3-carene. Catalytic hydrogenation of the dimethylene offered further proof for
the proposed structure of the diene. The spectral data on the hydrogenated product indicated that it was
1,1,2,3-tetramethylcyclopropane.
(Formula not captured by OCR) (Formula not captured by OCR) I,
I^ ,
/ /
STERIC' EFFECTS IN o - ( N ,N-DISUBSTITUTEmEENO) -T HI0PHEN0LS
SYNTHESIS OF I , Ir-DIMETHYL-2? 3-EIMETHYLENECYCLQPROPANE FROM
DELTA-3-CARENE
by
-
■ STEVEN >JAYNE MILLER
A t h e s e s s u b m itte d t o t h e G ra d u a te F a c u l t y i n p a r t i a l
f u l f i l l m e n t p f t h e R e q u i r e m e n ts f o r t h e .d e g r e e
of
■ DOCTOR OF PHILOSOPHY
C h e m i s tr y
A p p ro v e d :
C h a ir m a n , E x a m in in g O o z m itte e
G r a d u a t e D e an
MONTANA {STATE UNIVERSITY
B ozem an, M o n ta n a
A
M arch,, 19,72
Ji
AL
-iv -
ACKNOWLEDQMENIS
I w o u ld l i k e t o e x p r e s s my g r a t i t u d e t o my m a j o r P r o f e s s o r ,
A rn o ld C . C r a ig , f o r h i s g u id a n c e an d a s s i s t a n c e d u r in g t h e c o u r s e
o f g r a d u a t e s t u d y a t M o n ta n a S t a t e U n i v e r s i t y , My w i f e , H e le n ,
w as a c o n s t a n t i n s p i r a t i o n d u r i n g t h e m any r o u g h m o m en ts o f my
g ra d u a te s t u d i e s .
I n a d d i t i o n I w o u ld l i k e t o t h a n k my p a r e n t s ,
who s t o o d b e h i n d me f o s t e r i n g t h e d e s i r e t o a t t e m p t a n d c o m p le te
su ch an u n d e r ta k in g .
S p e c i a l t h a n k s g o e s t o B r a d f o r d P . M undy f o r t h e e q u ip m e n t
lo a n e d an d h i s p a t i e n t g u id a n c e 5 an d t o R od O tz e rib e rg e r, f o r th e
c o n s t r u c t i o n o f g l a s s w a r e a n d t h e m any h o u r s o f c o m p a n io n s h ip .
T h a n k s a l s o go t o J e r r y H u r l e y f o r h i s a s s i s t a n c e i n r u n n i n g t h e
m ass s p e c tr o m e t e r ,I
I w o u ld a l s o l i k e t o e x p r e s s my a p p r e c i a t i o n t o t h e D e p a r tm e n t
o f C h e m is tr y f o r p r o v id in g a G ra d u a te T e a c h in g A s s i s t a n t s h i p o r a
G r a d u a t e T u i t i o n A s s i s t a n t s h i p d u r i n g a m a jo r p o r t i o n o f t h e ti m e
a t t e n d i n g M o n ta n a S t a t e U n i v e r s i t y .
TABLE OF CONTENTS
page
V I T A« e o * c e o o e « > e » * ® e « i > * o f t e o 0 ® e * o O 6 O e o e e © o e e © o e e © O B O B » o « © e e © o o o e © c
3 -3 -
ACKNO-WIEDaMENT 3 e * e e e ®» * # ©» » o ®e ®e o » * 0 <, »©e®0 O»e ®i®p 6 » e e®e 6 e » e e e e e e
3-^T
LIST OF TABLES «#©#@*****»@0 * 0 ^®*®®®»*©»©©*©©*»®©©®®*®®®©©®©#®®©
V3-
LIST OF F IG U R E S .........................................................©__________
v ii
ABSTRACT _________________ ' ...................................................©©©................................ ..
Tiii
PART I — S t e r i c e f f e c t s i n o - (N 5N ^ d i s u b s t i t n t e d ) . t h i o p h e n o l s . ..............................
I - I 48
2
INTRODUCTION . . . . . . . . . . . . . . . . .
RESULTS AND DISCUSSION . . . . . .
e e ® # e o « e e
0 0 • ©e ©0
CONCLUSION .................. ..
EXPERIMENTAL . . .
' C o e e e o e o e
9
29
9 0 0 0
0 0 0 9 1
@009*00®
REFERENCES . . . .
30
U5
PART I I - - S y n t h e s i s p f I , l - d i m e t h y l - 2 5 3 - d i m e t h y l e n e ■ c y c lo p ro p a n e fro m d e l t a - 3- c a r e n e . . . . . . . . . . . . . . . . . . . . .
1 -6 5
INTRODUCTION . . . . . . . . . . . . , . , . 1* . * . . . . . . . . . . . . . . . . . . . . . . . . . .
2
RESULTS AND DISCUSSION ........................................... ........................................ .. .
12
CONCLUSION .................... . ............................................................... ........................
Ul
EXPERIMENTAL............................ .. ........................................ ......................................
U2
R EFE R EN C ES................................... .. . . . ........ ................................................. ..............
6O
-v i-
L IS T OF TABLES
PART I
TABLE I
TABLE I I
page
NMR ASSIGNMENTS FOR SUBSTITUTED
THIOPHENOLS
1 2 ,1 6
NMR ASSIGNMENTS FOR SUBSTITUTED
THIOANISOLES
1 7 ,1 8
PART I I
TABLE I
OZONOLTSIS OF D ELTA -3-0ARENE
23
TABLE I I
UV SPECTRUM OF I , l-D IM ETH Y L-2, 3-DIMETHYLENECYCLOPROPANE AND RELATED COMPOUNDS
31
NMR SPECTRUM OF I , l-D IM E T H IL -2 , 3 -DIMETHYLENECYCLOPROPANE AND RELATED COMPOUNDS
32
MASS SPECTRUM OF I , l-D IM E T H Y L -2, 3 -DIMETHYLENECYCLOPROPANE AND RELATED COMPOUNDS
33
MASS SPECTRUM OF 1 , 1 , 2 , 3^TETRAMETHYL~
CYCLOPROPANE AND RELATED COMPOUNDS
UO
TABLE I I I
TABLE IV
TABLE V
“ V ii—
LIST ' OF FIGURES
page
PART I
FIGURE I
FORMATION OF THE "METHYLENE BASE"
7
FIGURE 2
DECOMPOSITION OF 2 , 3 -DIMETHYLBENZOTHIAZOLIUM
IODIDE
8
FIGURE 3
PREPARATION OF THE STYRYL DIE
10
FIGURE k
DECOMPOSITION OF BENZOTHIAZOLIUM SALTS
12
FIGURE 3
DECOMPOSITION OF 3 -ALKYLBENZOTHEAZOLIUM
COMPOUNDS
13
FIGURE 6
METHYLATI ON OF THE THIOPHENOLS
Ik
FIGURE 7
Z AND E FORMS OF ANILIDES
22
FIGURE 8
PREFERRED CONFORMATION OF N-SUBSTITUTED
ANILIDES
2k
ENANTIOMERS OF N -E T H Y L -(o rth o -T H IO )ACETANILIDE
25
FIGURE 9
.
PART I I
FIGURE I
SCHEME I
" CONFORMATIONS OF DELTA-3 -C ARENE
SYNTHESIS OF I , l-L IM E T H Y L -2, 3 -DIMETHYLENECYCLQPR OPAEE
3
13
ABSTRACT
T h e p r o d u c t o b t a i n e d fr o m t h e a l k a l i n e h y d r o l y s i s o f t h e q u a ­
t e r n a r y s a l t , 2 - m e t h y l ~ 3 - e t h y l b e n z o t h i a z o l i u m i o d i d e , w as d e t e r m i n e d
t o h a v e t h e s t r u c t u r e show n b e l o w . T h i s p r o d u c t , o - ( N - e t h y l - N -
a c e t y l a m i n o ) - t h i o p h e n o l , g a v e r i s e t o a c o m p le x nm r s p e c t r u m . T h e
m e th y le n e p r o to n s o f t h e e t h y l p ro u p a p p e a re d t o b e n o n e q u iv a le n t
g i v i n g r i s e t o tw o s e t s o f e q u a l m u l t i p l e ! s . I f t h e m e th y le n e
p r o t o n s w e re e q u i v a l e n t , t h e n t h e y s h o u l d g i v e a q u a r t e t . B e c a u s e
o f t h i s n o n e q u i v a l e n c e , s e v e r a l r e l a t e d c o m p o u n d s, w i t h d i f f e r i n g
s t e r i c i n t e r a c t i o n s , w e re p r e p a r e d a n d fr o m t h e s e co m p o u n d s t h e s t e r i c
re q u ire m e n ts f o r r e s t r i c t e d r o t a t i o n aro u n d th e a r y l t o n itr o g e n bon d
w e re d e t e r m i n e d .
T h e nm r s p e c t r u m , u v s p e c t r u m a n d t h e m ass s p e c t r u m o f t h e
p r o d u c t o f t h e p y r o l y s i s o f I , l - d i m e t h y l - 2 , 3 - b i s - ( d i m e t h y l a m in o m e th y l) - c y c lo p r o p a n e d im e th o h y d ro x id e i n d i c a t e d t h a t I , 1 - d im e th y l2 , 3 - d i m e t h y l e n e c y c l o p r o p a n e h a d b e e n p r e p a r e d . T h e d im e th o h y d r o x i d e
w as s y n t h e s i z e d f r o m d e l t a - 3 - c a r e n e .
C a t a l y t i c h y d ro g e n a tio n o f
t h e d im e th y le n e o f f e r e d f u r t h e r p r o o f f o r t h e p ro p o s e d s t r u c t u r e
o f th e d ie n e .
The s p e c t r a l d a t a on th e h y d ro g e n a te d p ro d u c t i n ­
d i c a t e d t h a t i t w as I , I , 2 , 3 - t e t r a m e t h y l c y c l o p r o p a n e .
PART I
STERIC EFFECTS IN o-.(M,N-DISUBSTITUTEDAMIWO)-THIOPHEMOLS
-2 -
INTR ODUCTI ON
D u r i n g t h e i n v e s t i g a t i o n o f t h e ' h y d r o l y s i s o f c e r t a i n c y a n in e
dyes and q u a te rn a ry s a l t s
i t w as n o t e d t h a t c e r t a i n o f t h e p r o d u c t s
h a d u n u s u a l nm r s p e c t r a .
A f u r th e r and s y s te m a tic in v e s t i g a t i o n
in to th e o r ig in s o f th e s e u n u su a l s p e c tr a i s th e fo c u s o f t h i s
p o rtio n o f th e t h e s i s .
tro s c o p y i s
B ec a u se n u c l e a r m a g n e tic r e s o n a n c e s p e c ­
su ch a p o w e rfu l t o o l t o th e o rg a n ic c h e m is t and b e ­
c a u se i t p la y s a c e n t r a l r o l e i n th e re m a in d e r o f t h i s t h e s i s i t
is
a p p ro p ria te to
su m m a riz e t h e s a l i e n t f e a t u r e s
w h ic h a p p l y t o t h i s
o f t h e m e th o d
d is c u s s io n .
N u c le a r m a g n e tic re s p n ^ n c e s p e c tr o s c o p y h a s d e v e lo p e d i n t o
p o w e rfu l to o l f o r th e
o rg a n ic c h e m is t.
a
N o t o n l y i s nm r s p e c t r o s ­
c o p y o n e o f t h e c h e m i s t 's m o s t v a l u a b l e t o o l s f o r p r o b i n g t h e s t r u c ­
tu re
a n d s t e r e o c h e m i s t r y o f c o m p le x m o l e c u l e s , b u t i t
a ls o p ro v id e s
h im w i t h a m ean s o f s t u d y i n g i n t r a m o l e c u l a r m o v em en ts w i t h a c t i v a ­
t i o n e n e r g i e s o f 5> t o
2 5 k c a l . / m o le .
^
F o r e x a m p le , i t
i s w e ll
know n t h a t e q u a t o r i a l a n d a x i a l p r o t o n s o f c y c lo h e x a n e h a v e c o n s i d e r a b l y d i f f e r e n t c h e m ic a l s h i f t s .
a tu re ,
( 2)
H o w e v e r, a t ro o m t e m p e r ­
a l l t h e p r o t o n s o f c y c lo h e x a n e a p p e a r a s a s i n g l e n a r r o w
p e a k , due t o th e i n v e r s i o n o f th e r i n g .
When t h e t e m p e r a t u r e i s
s u f f i c i e n t l y l o w e r e d , s o t h a t t h e i n v e r s i o n c a n b e s e e n o n t h e nm r
-3 -
tim e s c a l e ,
s e p a r a t e p e a k s a r e s e e n f o r t h e a x i a l and t h e e q u a t o - -
‘
r i a l p ro to n s ,
(3)
^
I n o th e r w o rd s,
a t n o rm a l te m p e r a tu r e s , th e i n ­
v e rs io n o r f lip p in g
o f t h e c y p lo h e x a n e r i n g i s
t h e ranr t i m e s c a l e ,
and w hat i s
o b serv ed i s
fa s t,
a c c o rd in g t o
an av e rag e o f th e p ro to n s
N u c le a r m a g n e tic re s o n a n c e s p e c tr o s c o p y i s
a l s o o f g r e a t im ­
p o r ta n c e t o t h e o r g a n ic c h e m is t i n t h e d e t e c t i o n o f h in d e r e d r o t a ­
tio n about a bond in
in
a m o le c u le .
^
The r o t a t i o n
a m o le c u le c a n b e a f f e c t e d b y e l e c t r o n i c
aro u n d a bond
and s t e r i c
fa c to rs .
T h e m o s t o b v io u s e l e c t r o n i c f a c t o r w o u ld b e t h a t o f a d o u b l e b o n d
i n an a lk e n e .
A m o re s u b t l e e l e c t r o n i c f a c t o r w o u ld b e p a r t i a l
d o u b l e b o n d c h a r a c t e r a s i n a n a m id e .
The fo r e g o in g i s
re a d ily
s e e n i n t h e nm r s p e c t r u m o f d im et h y l f o r m a m i d e o r d i m e t h y l a c e t a m i d e
h3C\
/f
N -C (
H3 C
H
,
h
3
c
H izC
W
d "
XH
—U”
i n w hich, t h e gem d i m e t h y l g r o u p s i n e i t h e r c a s e a r e n o t e q u i v a l e n t .
( d)
a b o u t a b o n d .5 t h a t o f s t e r i c
The se c o n d r e a s o n a f f e c t i n g r o t a t i o n
h i n d r a n c e ; c a n b e s e e n i n t h e w e ll- k n o w n e x a m p le s o f t h e b i p h e n y l
d e r iv a tiv e s .'
T h is s t e p i c h in d ra n c e h a s a ls o b ee n o b se rv e d
in th e r o ta tio n ab o u t th e
b e n z a m id e s ( ^ 37 - 1 ).)
to n itro g e n bond in
a ry l to
ca rb o p y l bond in s u b s titu te d
benzophepones
a n ilin e s
N -a ry l p y rrp le s
and a ls o i n th e
ary l
5 n i t r o s o a n i l i n e s ^ ^ 3^ 3 ) ^
^ ^
and a n i l i d e s .
T h i s l a t t e r e x a m p le ^
t h a t o f s t e r i c h in d ra n c e i n th e r o t a t i o n
aro u n d th e a r y l to n itr o g e n
b o n d i n N ,N - d is u b s titu te d o -a m in o th io p h e n o ls ( N - s u b s t i t u t e d a c e t ­
a n ilid e s
) , w i l l b e t h e m a in c o n c e r n o f P a r t J o f t h i s t h e s i s .
H o w e v e r, t h i s
s tu d y o f s t e r i c a l l y h in d e re d r o t a t i o n i n
a n ilid e s
w as n o t a n o r i g i n a l a im o f t h e r e s e a r c h , b u t , i t a r o s e f r o m t h e
re s u lts
o b t a i n e d d u r i n g t h e c o u r s e o f tf o r k o n t h e o r i g i n a l p r o j e c t .
In itia lly ,
ly tic
th e r e s e a r c h p r o je c t in v o lv e d th e h y d r o ly tic
d e c o m p o s itio n o f r e p r e s e n t a t i v e c y a n in e d y e s .
w as o f i n t e r e s t ,
ic
T h is p r o je c t
a s t h e c y a n i n e d y e s a r e e m p lo y e d i n m any p h o t o g r a p h -
and b ip -m e d ic a l a p p lic a tio n s
a v a ila b le
(1 2 1 3 )
5
, b u t t h e r e w as n o i n f o r m a t i o n
a s t o t h e i r mode o f d e c o m p o s i t i o n i n s o l u t i o n ,
o r i n l i v i n g s y s te m s .
S in c e t h e r e i s
b e o f im p o rta n c e t o
on s u r f a c e s
c o n s id e r a b le i n t e r e s t and
i n v e s t i g a t i o n o f t h e c y a n in e s i n t h e b io - m e d ic a l f i e l d ,
to
and p h o to -
i t w o u ld
g a i n k n o w le d g e o f t h e i r h y d r o l y t i c r e a c t i o n s
a id in in te r p r e tin g
a n d u n d e r s t a n d i n g p o s s i b l e m odes o f a c t i o n .
r?
-5 -
I t c o u ld b e t h a t th e
o b serv ed b io lo g ic a l a c t i v i t y
o f som e o f t h e
c y a n in e d y e s a r o s e fro m a h y d r o l y s i s p r o d u c t o r p r o d u c ts r a t h e r
th a n th e i n t a c t dye m o le c u le .
Two r e p r e s e n t a t i v e c y a n i n e d y e s w e re s u b j e c t e d t o n e u t r a l a n d
a lk a lin e h y d ro ly s is .
The r e a c t i o n m ix tu r e o f t h e
a lk a lin e h y d ro ly s is
o f t h e d y e s c o n t a i n e d s e v e r a l p r o d u c t s , w h ic h w e re v e r y d i f f i c u l t
to
s e p a r a t e b y c o lu m n c h r o m a t o g r a p h y .
B ecause o f t h i s
i n s e p a r a t i o n , i t w as d e c i d e d t o l o o k i n t o t h e
o f th e q u a te rn a ry s a l t ,
d iffic u lty
a l k a l i n e d e c o m p o s itio n
2- m e t h y l - 3 - e t h y l b e n z o t h i a z o l i u m i o d i d e ,
w h ic h w a s a s t a r t i n g m a t e r i a l i n t h e p r e p a r a t i o n o f t h e c y a n in e d y e s
used.
The b e h a v io r o f b e n z o th ia z o liu m s a l t s to w a rd s a l k a l i h a s b e e n
know n s i n c e 1 9 2 3 , w h en M i l l s , C l a r k a n d A e s c h le m a n n c h a r a c t e r i z e d
t h e p r o d u c t o b t a i n e d f r o m t h e b a s i c h y d r o l y s i s o f 3- m e t h y l b e n z o t h i a z o liu m i o d i d e .
^
T h i s r e a c t i o n w as show n t o b e r e v e r s i b l e
b y a l m o s t c o m p l e t e r e c o v e r y o f 3 - m e t h y l b e n z o t h i a z o li u m i o d i d e u p o n
a d d itio n o f h y d ro g e n io d id e .
S in c e 1923 s e v e r a l a r t i c l e s h ave
-6 a p p e a r e d o n t h e s u b j e c t o f b e n z o t h i a z o l i u m com p o u n d s r e a c t i n g w i t h
a lk a li.
^^
I n 1925» C l a r k r e p o r t e d t h a t t h i s
sam e t y p e o f
r e a c t i o n t o o k p l a c e w i t h b e n z o t h i a z o l i u m com p o u n d s t h a t w e re a l s o
s u b s titu te d in th e 2 p o s itio n .
He a l s o r e p o r t e d t h a t t h i s
r e a c t i o n , w ith an a l k y l s u b s t i t u e n t i n th e
th ia z o liu m r in g ,
2 p o s itio n o f th e b en zo -
p r o c e e d e d t h r o u g h a " m e th y le n e b a s e " .
1939» Mumm p r e d i c t e d t h a t t h e
(1 7 )
" m e th y le n e b a s e " c o n s i s t e d o f a d im e r
. (18)
w h o se s t r u c t u r e w a s :
H o w e v e r, i n 1 9 6 1 , L a r i v e a n d D e n n i l a u l e r p r e d i c t e d t h a t t h e d i m e r ,
b a s e d on i t s
c h e m ic a l r e a c t i o n s
h ad th e fo llo w in g s t r u c t u r e :
( 22)
(2 3 )
,
and l a t e r on i t s
nm r s p e c tr u m ,
-7 -
ch3
H C =
CH-z
CH3
T h i s " m e th y le n e b a s e " c a n b e c o l l e c t e d a n d p u r i f i e d a n d s u b j e c t e d
to
fu r th e r re a c tio n s .
(21 2 2 )
>
T h e s u s p e c t e d mode o f f o r m a t i o n o f t h e
g iv e n i n f ig u r e I .
FIGURE I
^
" m e th y le n e b a s e " i s
I f th e b a s e u s e d i s th e h y d ro x id e io n ,
— FORMATION OF THE "METHYLENE BASE"
(23)
-8 t h e n t h e p r o d u c t o b t a i n e d d e p e n d s u p o n w h e th e r d i l u t e
t r a t e d h y d ro x id e i s u s e d a s c a n b e s e e n i n f i g u r e
2.
o r concen(2 5 )
FIGURE 2 — DECOMPOSITION 0F 2 , 3 -DIMETHYLBENZOTHIAZOLIUM IODIDE
( 2$ )
U pon r e a c t i o n o f c e r t a i n b e n z o t h i a z o l i u m q u a t e r n a r y s a l t s w i t h
d i l u t e h y d ro x id e io n , th e p r o d u c ts o b ta in e d gave r i s e t o
n u c l e a r m a g n e tic re s o n a n c e s p e c t r a .
c o m p le x
T h i s c o m p l e x i t y r e s u l t e d fr o m
t h e a p p a r e n t n o n e q u iv a le n c e o f m e th y le n e p r o to n s and c a n b e r a t i o n ­
a l i z e d b y a r g u m e n ts c o n c e r n i n g t h e
s t e r i c h in d ra n c e i n th e r o t a t i o n
a b o u t t h e a r y l t o n i t r o g e n b o n d i n t h e s e c o m p o u n d s.
~9~
RESULTS AND DISCUSSION
I.
HYDROLYTIC AND PHOTOLYTIC DECOMPOSITION OF CYANINE DYES
A lt h o u g h t h i s i s n o t t h e m a in a s p e c t o f P a r t I
of th is th e s is ,
i t w as t h o u g h t t h a t t h e w o rk d o n e s h o u l d b e b r i e f l y i n c l u d e d .
Two
o f t h e c y a n i n e d y e s t h a t w e re c o n s i d e r e d w e re co m p o u n d s I a n d 2
sh o w n b e l o w .
T h e s e tw o d y e s w e re s u b j e c t e d t o n e u t r a l a n d a l k a l i n e
2 -p-DIMETHYLAMINOSTYRYL-3-ETHYLBENZ0IHIAZOLIUM IODIDE
( r e f e r r e d t o a s "STYRYL" d y e )
3 -E T H Y L -2 -( 3 -(3-ETHYL-2-BENZOTH IAZ0LINYLIDENE) PROPENYL) BENZCTHIAZOLIUM
IODIDE
( r e f e r r e d t o a s "THC" d y e )
-1 0 -
h y d ro ly s is .
I n b o t h c a s e s t h e d y e s w e re u n a f f e c t e d b y n e u t r a l
h y d r o l y s i s , b u t w e re c o m p l e t e l y d e g r a d e d t o o t h e r co m p o u n d s b y
a lk a lin e h y d ro ly s is .
T h e p r o g r e s s o f t h e h y d r o l y s i s w as f o l l o w e d
b y o b s e r v in g t h e i r r e s p e c t i v e u l t r a v i o l e t - v i s i b l e
s p e c tr a and i t
w as n o t e d t h a t d y e I r e a c t e d m uch f a s t e r t h a n d y e 2.
I n b o th c a s e s ,
t h i n l a y e r c h ro m a to g ra p h y o f t h e r e a c t i o n m ix tu r e r e v e a l e d s e v e r a l
s p o t s t h a t w e re c l o s e t o g e t h e r ,
c o lu m n c h r o m a t o g r a p h y .
and v e r y d i f f i c u l t t o
H o w e v e r, i n t h e c a s e o f d y e I ,
s e p a ra te by
th e le a d in g
f r a c t i o n w as s e p a r a t e d a n d d e t e r m i n e d t o b e com pound 3 , p - d i m e t h y l a m in o b e n z a ld e h y d e ( b y t h i n l a y e r c h r o m a t o g r a p h y , g a s c h r o m a to g r a p h y
and b y i t s
nm r ) .
As c a n b e s e e n i n f i g u r e
H
0
8
3 , t h e s t y r y l dye i s
3
FIGURE 3 — PREPARATION OF STYRYL DYE
-1 1 -
p r e p a r e d b y t h e r e a c t i o n of- 2 - m e t h y l - 3 - e t h y l b e n z o t h i a z o l i u m i o d i d e
w i t h p - d i m e t h y l a m i n o b e n z a ld e h y d e i n t h e p r e s e n c e o f p i p e r i d i n e „
F ro m t h i s
it
a p p e a r s t h a t d y e I m i g h t b e d e c o m p o se d a s i t w as fo rm e d ,,
h o w e v e r n o o t h e r p r o d u c t s fr o m t h e o r i g i n a l r e a c t i o n m i x t u r e w e re
c h a ra c te riz e d .
A l s o n o p r o d u c t s w e re c h a r a c t e r i z e d f r o m t h e a l k a l i n e
h y d r o ly s is o f dye 2 .
B o th c y a n i n e d y e s w e re a l s o s u b j e c t e d t o p h o t o l y t i c d e c o m p o s i­
t i o n , how ever a g a in th e p ro d u c ts c o u ld n o t be i d e n t i f i e d .
T h e m a in
d i f f i c u l t y se e m e d t o b e t h e s o l u b i b i t y o f t h e c y a n i n e d y e s i n t h e
s o lv e n ts u se d .
T h e i o d i d e d y e s w e re c o n v e r t e d t o t h e c h l o r i d e d y e s ,
w h ic h g i v e s a t e n f o l d i n c r e a s e i n t h e i r s o l u b i l i t y , b u t s t i l l no
p r o d u c t's c o u l d b e c h a r a c t e r i z e d .
The q u a te rn a ry s a l t ,
2 -m e th y l-3 -
e th y lb e n z o th ia z o liu m io d id e ,w a s a l s o s u b je c te d t o p h o t o l y t i c d e ­
c o m p o s itio n .
T h e m a jo r p r o d u c t o b t a i n e d i n t h i s
c a s e w as t h e sam e
as th e h y d r o ly s is o f th e q u a te r n a ry s a l t i n an a lk a lin e s o lu tio n
( t h i s w as sh o w n b y t h i n l a y e r c h r o m a t o g r a p h y , g a s c h r o m a to g r a p h y
and b y i t s
II,
nm r s p e p t r u m ) .
ALKALINE DECOMPOSITION OF BENZOTHIAZOLIUM SALTS
F i g u r e I4 d e m o n s t r a t e s t h e r e a c t i o n o f c e r t a i n b e n z o t h i a z o l i u m
s a l t s w ith a l k a l i .
M ie n t h e r e i s
a m e t h y l g ro u p i n t h e 2 p o s i t i o n
o f th e b e n z o th ia z o liu m r i n g , th e p ro d u c t o b ta in e d d ep en d s upon th e
-1 2 -
10
R =C H 3
IL
R-CH2CH3
R
12
R=CH2 (|)
SHP
\±
R=CH2CH3
15
R=CH2 (J)
SH0
N Z 0 x CH3O
R
J3_ R=CH3
FIGURE b — DECOMPOSITION OF BENZOTHIAZOLIUM SALTS
c o n c e n t r a t i o n o f th e h y d ro x id e io n a s s h o rn b e f o r e i n f i g u r e
2.
I n t h e c a s e o f 2 - m e t h y l - 3 - b e n z y l b e n z o t h i a z o l i u m . b r o m id e a n d 2 m e t h y l - 3- e t h y l b e n z o t h i a z o l i u m i o d i d e
R - CH^ a n d R t = 0 ^ - 0
w as p r e p a r e d i n
tu re s
o f th e
( re fe rrin g to
a n d CHgCH^ r e s p e c t i v e l y ) t h e
a d d itio n to th e r in g
fig u re U —
" m e th y le n e b a s e "
o p e n e d co m p o u n d .
The s t r u c ­
" m e th y le n e b a s e s " a r e sh o w n b e lo w a n d t h e i r mode o f
f o r m a t i o n w as show n b e f o r e i n f i g u r e I .
When t h e r e i s
no a lk y l s u b s t i t u t e n t i n th e 2 p o s i t i o n o f th e
-1 3 -
17
16
b e n z o t h i a z o l i u m r i n g , t h e r e i s n o f o r m a t i o n o f a " m e th y le n e b a s e "
and th e s u s p e c te d ro u te t o th e r in g
fig u re
o p e n e d com pound i s
g iv e n i n
^ ° '>
FIGURE 5 — DECOMPOSITION OF 3-ALKYL BENZOTHIAZOLIUM COMPOUNDS
-I llT a b le I
sh o w s t h e r e s u l t s
s a l t s w ith a l k a l i ,
i n c l u d i n g t h e n u c l e a r m a g n e tic r e s o n a n c e a s s i g n ­
m e n ts f o r t h e p r o d u c t s .
m e th y la tio n o f th e
o f t h e r e a c t i o n o f b e n z o th ia z o liu m
T a b l e I I r e p r e s e n t s t h e r e s u l t s fr o m t h e
a b o v e p r o d u c t s a s show n i n f i g u r e 6 .
J8_ R =
R1= CH3
19 R-CH3 i Rt-CH2CH3
2 0 R=H ,R1=CH2CH3
21 R=H
,R - CH3
2 2 R=H
,R=CH2 O
FIGURE 6 — METHYLATION OF THE THIOPHENOLS
A ls o , fo llo w in g th e r e s u l t s i n T a b le s I
illu s tra tiv e
and I I ,
n u c l e a r m a g n e tic re s o n a n c e s p e c t r a .
th e re
are
T h ese in c lu d e
b o t h com p o u n d s t h a t e x h i b i t e d c o m p le x s p e c t r a a n d t h o s e t h a t e x ­
h i b i t e d n o rm a l s p e c tr a .
As p r e v i o u s l y s t a t e d , c e r t a i n b e n z o t h i a z o l i u m c o m p o u n d s, s u b ­
s t i t u t e d i n th e 2 and 3 p o s i t i o n s , r e a c t e d w ith a l k a l i t o y i e l d
a n i l i d e s t h a t e x h i b i t e d c o m p le x n u c l e a r m a g n e t i c r e s o n a n c e s p e c t r a .
S in c e t h i s
ab o u t th e
c o m p l e x i t y a p p e a r e d t o r e s u l t fr o m h i n d e r e d r o t a t i o n
a ry l to n itro g e n bond, i t
is
p e r tin e n t to d is c u s s th e
-1 5 table
STARTING
COMPOUNDS
PRODUCTS
i
nm r ASSIGNMENTS FOR THE
PRODUCTS (DELTA U N ITS)*
<t>
7 .2 0 (M)
NCH3
3.1 7 (S) E
CHtz
J 0 CH3
_£L
L
7 .9 8 (S)
<t>
7 .4 0 (M)
NCH2 CH3
3 . CO(Cl)E
NCHoCH-i
1.15(7)
Eh
8 .0 5 (S )
//SH
-G-
W L y /C H
7 . 10 (S)
CH2
CH2
NCH? $
4 . 8 0 (S)
0
0
O
Ii
CH
8 .0 3 (S )
6_
J2_
S = SINGLET, D = DOUBLET, T = TRIPLET, Q=QUARTE t , M= MULTI PLET
E = EQUIVALENT,
NE = NONEQUIVALENT
- 16 -
TABLE I
4)
7 . 4 0 (M)
NCH3
3 . 2 5 (S) E
S?CCH3
I.S O ( S )
<D
7.40(M )
NCHpCH3
4 . 1O(M) NE
3 .4 0 ( M )
NCHpCH-x
1 . 2 0 (T)
ft
1.7 5 (S)
^
CCH3
7.30(M )
5.50(D )
4 . 3 0 ( D ) NE
1 . 9 0 (S)
ft
7 .3 0 ( M )
I
NCH2 CH3
3 .7 0 (0 ) E
N CH2CH3
I. IO(T)
ft
1. 7 5 ( S )
CCH3
-1 7 table
II
METHYLATION PRODUCTS
20
nm r ASSIGNMENTS FOR THE
PRODUCTS (DELTA UNITS)
d>
7 . 2 0 (M)
NCH
3 . 2 0 (S)
SCH3
2 . 4 0 (S)
9
CCHx
1 . 8 0 (S)
<D
7 . 3 0 (M)
N CH^CH3
4 . 1 0 (M) kjc
3 . 2 0 (M) N t
NCH2 CH3
1 . 1 0 ( T)
SCH3
2 . 4 5 (S)
9
CCH3
1 . 7 0 (S)
<t)
7 . 3 0 (M)
NCH2 CH3
3 . 7 0 (Q) E
NCH2 CH3
M O (T)
SCH3
2 . 4 0 (S)
9
8 . 0 0 (S)
E
- 18 TABLE I I
7.15 (M)
3 .1 2 (S)
E
2 . 3 8 (S)
7 . 9 5 (S)
7 . 1 0 (M)
4 . 8 0 (S) E
2 . 3 I (S)
8 . 0 3 (S)
22
-X 9 —
SPECTRUM OF o-(N-ETHYL-N-ACETYLAM INO)-THIOM ISOLE,19
N-C ^CH3
SPECTRUM OF o -(N -B E N Z Y L -N -A C E T Y L A H N O )-T H IO P H E N O L ,l5
-20-
SPECTRUM OF o - (N-METHYL-N-ACETYLAMINO) -T HIOPHENOL,
SPECTRUM OF o -(N -E T H T L -N -A C E T Y L A H N O ) -T H I OPHENOL^lU
-2 1 -
SPECTRUM OF o - (N-METHH j-N-ACETYLAMINO)-THIOAMISOLE,l 8
SPECTRUM OF o - (N-ETHYL-N-FORMYLAMNO) -THIOPHENOL, 1 1
-2 2 c o n fo rm a tio n o f an a n i l i d e .
is
I t i s w e l l know n t h a t t h e
p la n a r , o r n e a r ly so
g iv in g r i s e
a z n id o -g ro u p
t o tw o f o r m s o r c o n f o r -
A
B
FIGURE 7 — Z AND E FORMS OF ANILIDES
m a tio n s o f th e a n i l i d e s .
F o rm A, c a l l e d t h e Z , e n d o o r c i s fo r m ,
h a s th e oxygen o f th e c a rb o n y l c i s t o th e b en zen e r i n g
a n d fo rm B ,
c a l l e d t h e E , e x o o r t r a n s fo r m , h a s t h e o x y g e n o f t h e c a r b o n y l
tr a n s to th e benzene r in g .
(^ ,U U - ^ O )
^ ie n R
Ri
a s i n t h e c a s e o f f o r m a n il i d e , t h e p re d o m in a te is o m e r i s
fo rm .
h y d ro g e n s,
th e B
H o w e v e r, b o t h t h e A a n d B fo r m c a n b e s e e n i n t h e n u c l e a r
m a g n e t i c r e s o n a n c e s p e c tr u m o f f o r m a n i l i d e . ^
^
fo rm a n ilid e ,
i n th e p la n e
th e
p la n e
o f th e
a m id o -g ro u p l i e s
M o st l i k e l y w i t h
o f th e
-2 3 -
benzene rin g ,
^^ z
t h u s g i v i n g m aximum d e l o c a l i z a t i o n o f e l e c t r o n s
H o w e v er t h i s w o u ld n o t b e t h e c a s e i f t h e r e w e re s t e r i c h i n d r a n c e
in v o lv e d i n t h i s
ed fo r m a n ilid e .
c o p la n a r a rra n g e m e n t,
^
'
T hen th e d i h e d r a l a n g le ( . i . e .
b e tw e e n t h e p la n e o f t h e
rin g
a s w ith a n o rth o s u b s t i t u t t h e a n g le
a m id o - g r o u p a n d t h e p l a n e o f t h e b e n z e n e
) w o u ld n o l o n g e r b e z e r o .
T he c o n fo rm a tio n e x p r e s s e d b y fo rm A i s
fo rm w hen R i s
a ls o th e p r e f e r r e d
a lk y l, b u t R ' i s h y d ro g e n .
H o w e v e r,
p r e s e n c e o f a n a l k y l s u b s t i t u t e n t o n t h e a n i l i d e n i t r o g e n ato m
c o m p l e t e l y r e v e r s e s t h e c o n f o r m a t i o n a l p r e f e r e n c e o f t h e m o le ­
c u le .
)
I n o t h e r w o rd s w hen R ' i s
an a l k y l g ro u p an d R i s
a h y d ro g e n o r an a l k y l g ro u p , th e p r e f e r r e d c o n fo rm a tio n i s th e
B fo rm w i t h t h e o x y g en o f t h e c a r b o n y l g ro u p t r a n s t o t h e b e n z e n e
rin g ,
rin g .
a n d th e . p l a n e o f t h e a m id o - g r o u p o r t h o g o n a l t o t h e b e n z e n e
An o r t h o s u b s t i t u t e n t i n t h e
t h e c o p l a n a r a r ra m g e m e n t o f t h e
a n ilid e rin g
a ls o h in d e rs
a m id o - g r o u p a n d t h e b e n z e n e r i n g
(31)
c a u s in g t h e d i h e d r a l a n g le t o b e g r e a t e r t h a n 0 d e g r e e s . w
d ia g ra m o f t h i s p r e f e r r e d c o n f o rm a tio n i s
th is
phown i n f i g u r e 8 .
A
A g a in
c o n fo rm a tio n i s p r e f e r r e d f o r a n i l i d e s t h a t h av e an a lk y l
g ro u p i n s t e a d o f a h y d ro g e n f o r R g .
o f t h e co m p o u n d s l i s t e d i n T a b l e s I
As t h i s i s th e ease fo r a l l
and I I ,
fig u re 8 re p re s e n ts
t h e p r e f e r r e d c o n f o r m a t i o n f o r t h e s e c o m p o u n d s.
D e p e n d in g u p o n t h e s i z e s
o f t h e g r o u p s R ^ , R ^ a n d R_ i n f i g u r e
-2 k-
FIGURE 8 — PREFERRED CONFGRMA.TION OF N-SUBST I T UTED ANILIDES
8, t h e r e ca n b e h in d e re d r o t a t i o n aro u n d th e a r y l t o n itr o g e n bon d .
C om pounds 1 0 , IR. a n d lU i n T a b l e s I
and I I g iv e r i s e
to
c o m p le x
n u c l e a r m a g n e tic re s o n a n c e s p e c t r a t h a t c a n b e r a t i o n a l i z e d on th e
b a s is
o f h in d e re d r o ta t i o n
about th e
a r y l to n itro g e n bond.
In
p a r t i c u l a r , tw o e n a n t i o m e r i c f o r m s c a n b e w r i t t e n f o r com pound
1 0 a s sh o w n i n f i g u r e 9 .
As l o n g a s t h e r e
i s h in d e re d r o ta tio n
a b o u t t h e a r y l t o n i t r o g e n b o n d , t h e m i r r o r i m a g e s , IOA a n d IO B,
a r e n o n s u p e rim p o s a b le .
o r IO B , i t
If
a m o d e l i s m ade o f e i t h e r com pound IQA
can be seen th a t th e re i s
ab o u t th e e th y l to n itro g e n bond.
Hg a r e d i a s t e r e o m e r i c ; t h a t i s w hen
r e l a t i v e l y u n h in d e re d r o t a t i o n
H o w e v e r, t h e h y d r o g e n s
is
-SH g r o u p o n t h e a c e t a n i l i d e , Hg i s n o t ,
and
i n th e p ro x im ity o f th e
and v ic e v e r s a .
T he t e r m
-2 5 -
f ig u r e
9 — ENANTIOMERS OF N-ETHYL-(ORTHO-THIO)-ACETANILIDE
" d ia s te r e o t o p i c " h a s b e e n s u g g e s te d t o d e s c r ib e th e above n o n e q u i v a l e n t m e th y le n e p r o to n s b y H is lo w an d R a b a n .
(5 2 )
T hey s t a t e
t h a t g r o u p s a r e d i a s t e r e o t o p i c i f t h e y h a v e t h e sam e c o n s t i t u t i o n ,
r e s i d e i n d ia s t e r e o m e r i c e n v iro n m e n ts , an d c a n n o t b e in te r c h a n g e d
b y a n y sy m m e try o p e r a t i o n .
T h e p r o t o n s , H^ a n d Hg i n f i g u r e 9 a r e n o t m a g n e t i c a l l y e q u i v ­
a le n t.
T hey c a n o n ly b e m a g n e tic a lly e q u iv a le n t i f t h e r e i s u n ­
h in d e re d r o t a t i o n
a b o u t t h e a r y l t o n i t r o g e n b o n d o r i f t h e tw o
-2 6 o r t h o p o s i t i o n s o n t h e a c e t a n i l i d e c o n t a i n t h e sam e g r o u p i n g .
S i d d a l l and P ro a s k a h av e d e m o n s tra te d t h i s
s e c o n d m e th o d b y o b s e r v ­
i n g e q u i v a l e n t m e t h y l e n e p r o t o n s i n t h e com pound show n b e lo w . ^
In t h i s case th e re i s
th e
a p l a n e o f sy m m e try w h ic h i s
i n th e p la n e o f
a m id o - g r o u p a n d p e r p e n d i c u l a r t o t h e p l a n e o f t h e b e n z e n e r i n g .
H o w e v e r, i n t h e c a s e o f com pound 1 0 , t h e m o l e c u l e h a s n o sy m m etry
e le m e n t.
N - e t h y l a c e t a n i l i d e , com pound 12 i n T a b l e I ,
a l s o show s
e q u iv a le n c e o f t h e m e th y le n e p r o t o n s o f t h e e t h y l g ro u p .
p r o b a b ly due t o th e u n h in d e re d r o t a t i o n
bond.
T h is i s
ab o u t th e a r y l to n itro g e n
E v e n i f t h e r e w e re s t e r i c h i n d r a n c e t o r o t a t i o n
about th is
b o n d , t h e r e w o u ld s t i l l b e a p l a n e o f sy m m e try a n d t h e m e th y le n e
p r o t o n s w o u ld b e e q u i v a l e n t .
T h i s m e th o d o f e x p l a i n i n g n o n e q u i v a l e n t m e t h y l e n e p r o t o n s
b e c a u se o f h in d e re d r o t a t i o n
a b o u t an a r y l t o n itr o g e n bo n d i n an
-2 7 -
o r t h o s u b s t i t u t e d a c e t a n i l i d e h a s b e e n u s e d b e f o r e . ( - ^ j 3.7 j 20 , 21 .)
T h is i s t h e f i r s t tim e t h a t t h e
o r t h o - s u b s t i t u t e n t h a s b e e n a -SH
o r -SCH^ g r o u p . '
It
is
a ls o
o f i n t e r e s t to ' n o te f o r a l l o f th e
d e r i v a t i v e s i n T a b le p I
and I I
( i.e .
a c e ta n ilid e
com p o u n d s 9 - l U
) th a t th e ir
n u c l e a r m a g n e tic re s o n a n c e s p e c t r a d i d n o t in c lu d e a d d i t i o n a l s p l i t ­
tin g
d u e t o t h e tw o i s o m e r s t h a t c a n b e w r i t t e n f o r a m id e s ( fo r m s
A and B i n f ig u r e
7 ) »
H o w ev er t h e d e r i v a t i v e s o f f o r m a n i l i d e
( co m p o u n d s 6 - 8 , 1 5 - 1 7 ) d i d s h o w . a d d i t i o n a l s p l i t t i n g .
have b een o b se rv e d b e fo re ,
( l 6 , 21 , 2 U)
T hese f a c t s
one i n s t a n c e ,
even
a t lo w t e m p e r a t u r e , n o s e c o n d s e t s o f nm r s i g n a l s w e re o b s e r v a b l e
f o r th e a c e ta n ilid e s under in v e s tig a tio n .
d i s u b s t i t u t e d a m id e s c a n e x i s t i n
The f a c t t h a t a c y c lic
a Z a n d E fo r m i s w e ll - k n o w n .
f 3)
T h e a b s e n c e o f o b s e r v a b l e a m id e i s o m e r i s m i n co m p o u n d s 9 - l U c o u l d
d e p e n d o n e i t h e r o f tw o e x p l a n a t i o n s
t h e a m id e b o n d i s
^
^ : (l)
ro ta tio n
aro u n d
to o r a p id , th u s n o t a llo w in g s u f f i c i e n t l i f e t i m e s
o f t h e tw o f o r m s o n t h e n u c l e a r m a g n e t i c r e s o n a n c e t i m e s c a l e t o
b e o b s e r v a b l e j o r ( 2 ) th e rm o d y n a m ic a l l y ,
o n e a m id e i s o m e r i s
so
m uch m o re s t a b l e t h a n t h e o t h e r t h a t t h e p o p u l a t i o n o f t h e l e s s
s t a b l e is o m e r i s
t o o lo w t o p e r m i t i t s
d i r e c t o b s e rv a tio n , i . e .
l e s s t h a n a b o u t 1 %.
One e x p e r i m e n t t h a t s h o u l d b e ru n - o n com p o u n d s .1 0 , 1 1 a n d lU
i n T a b le s I
and I I i s
a v a r i a b l e te m p e r a tu r e n u c l e a r m a g n e tic
-2 8 -
re s o n a n c e s p e c tr u m .
I f t h e t e m p e r a t u r e a t w h ic h t h e tw o s e t s o f
m u l t i p l e t s i n com pounds. 1 0 , 11 a n d lU c o a l e s c e c a n - b e d e t e r m i n e d ,
th e n t h e b a r r i e r h e i g h t s ( i n k i l o c a l o r i e s p e r m o le .) t o r e s t r i c t e d
r o t a t i o n .c a n b e c a l c u l a t e d f o r t h e s e c o m p o u n d s .
(2 0 21 23 2 ii)
^ ^ 5
T h is
f u r t h e r i n v e s t i g a t i o n w as n o t p u r s u e d d u e t o t h e l a c k o f a v a r i a b l e
t e m p e r a t u r e a c c e s s o r y f o r t h e V a r i a n A -6 0 s p e c t r o m e t e r .
-
29-
GONOLUSION
B e n z o th ia z o liu m s a l t s
rin g
opened p ro d u c ts .
do r e a c t , w ith , h y d ro x id e i o n t o y i e l d
D e p e n d in g u p o n t h e s u b s t i t u t e n t s i n t h e
2 a n d 3 p o s i t i o n s o f t h e b e n z o t h i a z o l i u m r i n g , t h e co m p o u n d s t h a t
a r i s e fro m r i n g c le a v a g e c a n g iv e r i s e
re so n an ce s p e c tr a .
to
c o m p le x n u c l e a r m a g n e t i c
T he c o m p le x s p e c t r a r e s u l t fr o m n o n e q u i v a l e n t
m e th y le n e p r o to n s i n t h e r i n g
opened p ro d u c ts .
In th is
s itu a tio n
t h e n o n e q u i v a l e n t m e th y le n e p r o t o n s a r e c a l l e d d i a s t e r e o t o p i c ,
w h ic h m ean s t h a t a l t h o u g h t h e y r e s i d e
th e y a ls o r e s id e
o n t h e sam e c a r b o n a to m ,
i n d ia s te r e o m e r ic e n v iro n m e n ts .
T h ese p ro to n s
a r e n o t m a g n e t i c a ll y e q u i v a l e n t and g iv e r i s e t o d i f f e r e n t c h e m ic a l
s h ifts .
The above h o ld s t r u e
o n l y w h en t h e r e i p h i n d e r e d r o t a t i o n
aro u n d th e a r y l t o n itr o g e n bond i n th e r i n g opened p r o d u c ts .
i s t h e c a s e i n f i g u r e 8 w hen
a n e t h y l g ro u p a n d R ^ i s
is
a -SH g ro u p , R^ i s
a t l e a s t a m e th y l g ro u p .
T h is
a t le a s t
M hen e i t h e r t h e
R ^ o r Rg g r o u p s a r e s m a l l e r , t h e n a n o r m a l s p e c tr u m i s
o b serv ed .
-3 0 -
EZPERIMEMTAt,
M e l t i n g p o i n t s w e re d e t e r m i n e d o n a F i s h e r J o h n s m e l t i n g p o i n t
a p p a r a tu s b e tw e e n g l a s s d i s c s o r i n u n s e a le d c a p i l l a r y tu b e s i n a
T h i e l e t u b e f i l l e d w i t h Dow C o r n in g 5 5 0 s i l i c o n e f l u i d
and a l l a re
u n c o r re c te d .
T h e p h o t o l y t i c d e c o m p o s i t i o n s w e re a c c o m p lis h e d - b y u s i n g a
H a n o v ia h i g h p r e s s u r e q u a r t z m e r c u r y v a p o r la m p ( l £ 0 v o l t s 5 1|3>0
w a t t s 1 7 , 3 i n c h e s a r c l e n g t h ; p r i n c i p l e w a v e l e n g t h s i n A n g s tr o m s :
3660, 5L61, 2780 ) .
T h e n u c l e a r m a g n e t i c r e s o n a n c e s p e c t r a w e re o b t a i n e d o n a
V a r i a n A s s o c i a t e s , I n c . , M o d e l A -6 0 s p e c t r o m e t e r .
T h e com pounds
w e re r u n i n e i t h e r c a r b o n t e t r a c h l o r i d e w i t h TMS a s a n i n t e r n a l
s t a n d a r d o r i n S il a n o r - G . ( CDCl^ w i t h 1% TMS ) „
The u l t r a v i o l e t - v i s i b l e
s p e c t r a w e re t a k e n i n
a b s o l u t e m e th a n o l
o r i n 90% m e t h a n o l ( w a t e r ) o n e i t h e r a B eckm an M o d e l DK-2 s p e c t r o ­
p h o t o m e t e r o r o n a G a ry M o d el lU s p e c t r o p h o t o m e t e r .
E l e m e n t a l a n a l y s e s w e re p e r f o r m e d b y G a l b r a i t h L a b o r a t o r i e s ,
I n c . , K n o x v ille , T e n n e sse e ,
**31™
I.
HYDROLITIG AMD PHOTOLITJC DECOMPOSITION OF CIAMlME DIES
HIDROLITIO CONDITIONS
1)
M e n tra l c o n d i t i o n s :
I n a t y p i c a l e x p e r i m e n t y .2 1 0 g ra m s ( .0 0 0 ^ 3 m o le s ) o f THCj
d y e 2 , w as p u t i n
a f l a s k w i t h e i t h e r k $0 m l a b s o l u t e m e t h a n o l
p l u s 5>0 m l d i s t i l l e d w a t e r o r $00 m l a b s o l u t e m e t h a n o l .
T he s o l u ­
t i o n w as c o v e r e d a n d m a g n e t i c a l l y s t i r r e d u n d e r n o r m a l a n d c o n s t a n t
ro o m i l l u m i n a t i o r j . ( f l u o r e s c e n t l i g h t s
no change i n th e u l t r a v i o l e t - v i s i b l e
2)
).
A f t e r o n e w e ek t h e r e w as
s p e c tr u m .
B a s ic c o n d i t i o n s :
D e c o m p o s it i o n o f d y e I :
I n a t y p i c a l e x p e r i m e n t 5 l .f ? g ra m s ( .0031). m o le s ) o f t h e
S t y r y l d y e , d y e I , w as d i s s o l v e d i n
75>0 m l o f a b s o l u t e m e t h a n o l .
T o t h i s w as a d d e d 32 m l o f a IM s o d iu m h y d r o x i d e s o l u t i o n ,
m i x t u r e w as c o v e r e d a n d s t i r r e d m a g n e t i c a l l y .
and t h i s
A f t e r one d ay th e
dye h a d decom posed.
D e c o m p o s it i o n o f d y e 2 :
In
a t y p i c a l e x p e rim e n t,
.1 3 3 g ra m s ( .0 0 0 2 7 m o le s ) o f THC,
d y e 2 , w as d i s s o l v e d i n 3 6 0 m l o f a b s o l u t e m e t h a n o l .
T o t h i s w as
-3 2 -
ad.ded I4O m l o f a .IM s o d iu m h y d r o x i d e s o l u t i o n ,
r e d m a g n e tic a lly f o r e ig h t d a y s.
a n d t h i s w as s t i r ­
T h e -u l t r a v i o l e t - v i s i b l e
s p e c tr u m
i n d i c a t e d t h a t t h e dye h a d decom posed.
I n b o th o f th e
t e m p t w as m ade t o
above c a s e s w ith a l k a l i n e h y d r o l y s i s ,
s e p a r a t e t h e d e c o m p o s i t i o n p r o d u c t s b y co lu m n
c h ro m a to g ra p h y , u s i n g A d s o r b o s il- 2
In c .
an a t ­
( A p p lie d S c ie n c e L a b o r a to r ie s ,
) as th e a b s o rb e n t and a v a r i e t y o f s o lv e n ts .
H o w e v e r, o n l y
o n e p r o d u c t fr o m t h e d e c o m p o s i t i o n o f d y e I w as a b l e t o b e c h a r a c t e r ­
iz e d ,
a n d n o p r o d u c t s fr o m t h e d e c o m p o s i t i o n o f d y e 2.
T h e one
p r o d u c t i d e n t i f i e d f r o m t h e d e c o m p o s i t i o n o f d y e I w as d e t e r m i n e d
t o b e p - d i m e t h y l a m i n o b e n z a ld e h y d e ( 3 ) b y i t s
nm r s p e c t r u m , i t s
g a s c h r o m a t o g r a p h a n d t h i n l a y e r c h r o m a to g ra m w i t h a n a u t h e n t i c
s a m p le .
PHOTOLTTIC CONDITIONS
B o th t h e i o d i d e s a n d t h e c h l o r i d e s o f d y e s I
j e c t e d t o p h o t o l y t i c d e c o m p o s itio n .
a n d 2 w e re s u b ­
A lth o u g h d e c o m p o s itio n d id
o c c u r , n o p r o d u c t s w e re c h a r a c t e r i z e d f r o m t h e r e a c t i o n m i x t u r e .
-3 3 -
D e c o m p o s it i o n o f d y e I ;
I n a t y p i c a l e x p e r i m e n t 5 .25U g ra m s ( .0 0 6 Ij. m o le s ) o f t h e
c h lo rid e
o f dye I i n
m l a b s o l u t e m e t h a n o l w as s u b j e c t e d t o
t h e H a n o v ia la m p r a d i a t i o n .
T h e la m p w a s c o o l e d i n
a q u a r tz w e ll.
A f t e r 3^g d a y s t h e s a m p le h a d t u r n e d c o l o r l e s s .
D e c o m p o s it i o n o f 2 - m e t h y l - 3 - e t h y l b e n z o t h i a z o l i u m i o d i d e
(8 ):
3 . 0 g ra m s ( .016 m o le s ) o f 2 - m e t h y l - 3 - e t h y l b e n z o t h i a z o lin m
io d id e
( 8 ) i n 1 3 0 m l w a t e r w as s u b j e c t e d t o t h e H a n o v ia lam p r a ­
d i a t i o n f o r tw o d a y s .
The c o l o r l e s s s o l u t i o n h a d t u r n e d p u r p le .
A lth o u g h t h e dye fo rm e d c o u ld n o t b e c h a r a c t e r i z e d ,
t o g r a p h y ( a lu m in u m o x i d e a n d c h l o r o f o r m
c o lu m n c h ro m a ­
) o f t h e r e a c t i o n m ix tu re
r e v e a l e d a co m pound w h o se nm r s p e c t r u m w as i d e n t i c a l w i t h t h a t o f
o - ( N - e t h y l - N - a c e t y l a m in o )- t h i o p h e n o l ( l U ) .
a ls o p re p a re d b y th e
th ia z o liu m io d id e
T h i s p r o d u c t w as
a l k a l i n e h y d r o l y s i s o f 2-m e th y l-3 - re th y lb e n z o -
(8 ).
P r e p a r a t i o n o f S t y r y l dye I :
8 . 0 g ra m s (
io d id e
.0 2 6 m o le s ) o f 2 - m e t h y l - 3 - e t h y l b e n z o t h i a z o l i u m
( 8 ) w as m ix e d w i t h 3 « 8 6 g ra m s (
.039 m o le s ) o f p - d i m e t h y l -
a m in o b e n z a ld e h y d e ( 3 ) i n 30 m l o f a b s o l u t e e t h a n o l .
a d d e d 2 . 3 g ra m s ( .0 2 6 m o le s ) o f p i p e r i d i n e
T o t h i s w as
a n d t h e m i x t u r e w as
a llo w e d t o r e f l u x f o r one h o u r , t h e n c o o le d and t h e s o l i d c o l l e c t e d .
-3ka f f o r d i n g 7 . 3 g ra in s (6%%) o f a c r y s t a l l i n e p r o d u c t .
fr o m 9$% e t h a n o l .
mp
Re c r y s t a l l i z e d
2 5 6 -2 3 7 ” C
P r e p a r a t i o n o f THC, d y e 2 :
1 0 .0
io d id e
g ra m s ( .0 3 3 m o le s ) o f 2 - m e t h y l - 3 ~ e t h y l b e n z o t h i a z o l i u m
( 8 ) w as m ix e d w i t h 9 . 7 g ra m s ( .0 6 6 m o le s ) o f t r i e t h y l -
o rth o fo rm a te i n 80 m l o f p y r id in e .
( .0 3 3 m o le s ) o f t r i e t h y l a m i n e
r e f l u x f o r tw o h o u r s .
T o t h i s w as a d d e d 3 . 3 g ram s
a n d t h e m i x t u r e w as a l l o w e d t o
T h e m i x t u r e w as t h e n c o o l e d a n d f i l t e r e d .
T h e r e r e m a i n e d 7 . 0 g ra m s ( 8 7 $ ) o f a c r y s t a l l i n e p r o d u c t .
t a l l i z e d fro m 95$ e t h a n o l .
mp
C o n v e rs io n o f th e io d id e o f dye
T o U.O g ra m s ( .0 0 9 3 m o le s
R ecry s­
2 6 9 -2 7 0 ”0
I
) of
to i t s
c h lo rid e :
dye I i n 100 m l
o f a b s o lu te
m e t h a n o l w as a d d e d U .3 g ra m s ( .0 3 m o le s ) o f f r e s h l y p r e p a r e d
s i l v e r c h lo rid e .
T h i s m i x t u r e w as s t i r r e d
h o u rs a n d - th e n f i l t e r e d .
U pon r e m o v a l o f s o l v e n t t h e r e r e m a in e d
2 . 7 g ra m s ( 8 5 $ ) o f a c r y s t a l l i n e p r o d u c t .
l i z e d fro m 95$ e t h a n o l .
and r e f lu x e d f o r e ig h t
mp
T h e d y e w as r e c r y s t a l ­
2 5 6 -2 5 7 ”C
C o n v e rs io n o f th e io d id e o f dye
2t o
i t s c h lo rid e :
T o 7 . 0 g ra m s ( .0 lU 2 m o le s
)of
d y e 2 (THC) i n 1 0 0
ml o f
a b s o l u t e m e t h a n o l w as a d d e d 8 . 0 g ra m s ( .0 5 6 m o le s ) o f f r e s h l y
-3 5 -
p re p a re d s ilv e r c h lo rid e .
T h i s m i x t u r e w as s t i r r e d
f o r 11 h o u rs and th e n f i l t e r e d .
and re flu x e d
U pon r e m o v a l o f s o l v e n t t h e r e
r e m a i n e d 1 , 9 g ra m s {33%) o f a c r y s t a l l i n e p r o d u c t .
fr o m 9$% e t h a n o l .
II.
mp
2 1 5 -2 1 9 * 0
R e c ry s ta lliz e d
.
ALKALINE DECOMPOSITION OF BENZOIHIAZOLIUM SALTS
P re p a ra tio n o f N -e th y la c e ta n ilid e :
1 . 0 g ra m ( .0 0 8 3 m o le s ) o f N - e t h y l a n i l i n e w as m ix e d w i t h 1 . 0
g ra m ( .0 0 9 8 m o le s ) o f a c e t i c
5 m in u te s .
a n h y d rid e and a llo w e d t o
s ta n d f o r
T h e r e a c t i o n m i x t u r e w as c o o l e d i n a n i c e b a t h a n d
d i s t i l l e d w a t e r w as a d d e d .
T h e r e a c t i o n m i x t u r e w as f i l t e r e d t o
y i e l d 1 . 0 g ra m { 1h%>) o f a c o l o r l e s s s o l i d .
mp
51 - 53 " C
P r e p a r a t i o n o f 3 - m e t h y l b e n z o t h i a z o l i u m i o d i d e , I;.;
1 0 . 0 g ra m s ( .07U m o le s ) o f b e n z o t h i a z o l e w e re m ix e d w i t h 2 0 . 0
g ra m s ( . l U m o le s ) o f m e t h y l i o d i d e
r e f lu x e d o v e r n ig h t.
to n e .
mp
a n d t h e r e a c t i o n m i x t u r e w as
T h e m i x t u r e w as f i l t e r e d
and w ash ed w ith a c e ­
T h e r e r e m a i n e d 1 0 .8 g ra m s (53% ) o f a c o l o r l e s s s o l i d .
2 0 5 - 2 0 7 ”C
P r e p a r a t i o n o f o - ( W - m e th y l- M ^ f o r m y la tm - n o ) - th io p h e n o l, 1 0 :
5>.6 g ra m s ( .0 2 m o le s ) o f 3 - m e t h y l b e n z o t h i a z o l i u m i o d i d e
(L ) w e r e d i s s o l v e d i n 2 ^ 0 m l o f w a t e r .
( . 3 1 m o le s ) o f p y r i d i n e
fo r 2 h o u rs.
T o t h i s w as a d d e d 25> m l
a n d t h e m i x t u r e w as a l l o w e d t o r e f l u x
T h e m i x t u r e w as e x t r a c t e d w i t h c h l o r o f o r m
( 3 X 75 m l )
a n d t h e c o m b in e d f r a c t i o n s w e re w a s h e d w i t h 1 0 $ h y d r o c h l o r i c a c i d
( 2 X 5 0 m l )„
A f t e r e v a p o r a tio n q f s o l v e n t t h e r e re m a in e d 2 ,5
g ra m s ( 7 5 # ) o f a c o l o r l e s s s o l i d .
met h a n o l .
mp
R e c r y s t a l l i z e d fro m a b s o lu te
1 1 0 - 1 1 2 °C
P r e p a r a t i o n o f o - ( H - m e t h y l - N - f o rm y la m in o ) - t h i o a n i s o l e / 2 1 :
1 .0
.
g ra m ( .0 0 6 m o le s ) o f o - ( N - m e th y l- N ~ f o rm y la m in o ) - t h i o -
p h e n o l , IO 5 w as d i s s o l v e d i n 2 0 m l o f 5 $ s o d iu m h y d r o x i d e „
g ra m s ( .0 2 2 m o le s
3 .1
) o f m e t h y l i o d i d e w e re a d d e d a n d t h e r e s u l t i n g
m i x t u r e w as m a g n e t i c a l l y s t i r r e d
o v e rn ig h t.
T h e m i x t u r e w as t h e n
e x t r a c t e d w ith c h lo ro fo rm an d u p o n e v a p o r a tio n o f th e s o lv e n t t h e r e
r e m a i n e d 0 . 9 g ra m s ( 83 $ ) o f a n o i l .
P r e p a r a t i o n o f 3 ^ -e th y lb e n z o th la z o liu m i o d i d e , 5 ;
lU .O g ra m s ( .IOlj. m o le s ) o f b e n z o t h i a z o l e w e re m ix e d w i t h
1 6 . 5 g ra m s ( .1 0 6 m o le s ) o f e t h y l i o d i d e .
w as f i l t e r e d
and th e r e s u l t i n g
( 3 X 1 0 m l ) and a llo w e d t o
T h i s r e a c t i o n m ix tu re
s o l i d w as w a s h e d w i t h c o l d a c e t o n e
d ry in
a ir.
T h e r e r e m a i n e d 1 6 . 3 g ra m s
-
(5>1$) o f a c o l o r l e s s s o l i d .
37-
mp
130° C
■P r e p a r a t i o n o f o - ( M - e t h y l " N ~ f o r m y l a m n o ) - t h i o p h e n o l , 1 1 :
T h i s com pound w as p r e p a r e d i n tw o w a y s :
1 . ■ 3 . 0 g ra m s ( .0 1 7 2 m o le s ) o f 3 - e t h y l b e n z o t h i a z o l i u m i o d i d e ? Jpj
w e re d i s s o l v e d i n lj.0 m l o f d i s t i l l e d w a t e r .
h y d ro x id e s o l u t i o n
a llo w e d t o
30 m l o f a
( ,0 6 2 m o le s ) w e re a d d e d a n d t h i s
s ta n d f o r 2 d ay s.
s o d iu m
s o l u t i o n w as
T h e r e a c t i o n m i x t u r e w as f i l t e r e d - t o
y i e l d 1 . 6 g ra m s ( 3 l $ ) o f a c o l o r l e s s s o l i d .
mp
1 1 3 - 1 1 6 'C
A n a l y s i s f o r C qH1 1 MOS
2.
C a lc u la te d
C - & . 6 h$ H -6 .1 2 % M -7.73/& S - 1 7 , 69 %
Found
G - 3 9 .3 3 ^ H - 6 . 00 ^ N - 7 .6 8 $ S - 1 7 . 83 ^
"
3 . 0 g ra m s ( .0 1 7 2 m o le s ) o f 3 - e t h y l b e n z o t h i a z o l i u m i o d i d e ,
w e re d i s s o lv e d i n 80 m l o f d i s t i l l e d w a te r .
20 m l o f a s a t u r a ­
t e d s o d iu m b i c a r b o n a t e s o l u t i o n w e re a d d e d a n d a l l o w e d t o
n ig h t.
s t i r o v e r­
T h e r e a c t i o n m i x t u r e w as f i l t e r e d t o y i e l d 2 . 0 g ra m s ( 6 3 $ )
o f a c o lo rle s s s o lid .
mp
1 1 3 -1 1 6 ° C
' P r e p a r a t i o n o f 0 - ( M - e t h y l- M - f o rm y la m in o ) - t h i o a n j s o l e , 2 0 :
1 .0
g ra m ( .0 0 3 3 m o le s ) o f 0 - ( N - e t h y l - M - f o rm y la m in o ) - t h i o -
p h e n o l , 1 1 , w as a d d e d t o
20 m l o f 3 $ s o d iu m h y d r o x i d e „
ad d ed u n t i l a l l t h e s o l i d d is s o lv e d ,,
E t h a n o l w as
3 , 1 g ra m s ( .0 2 2 m o le s ) o f
-3 8 -
m e t h y l i o d i d e w e re a d d e d a n d t h e r e s u l t i n g
m a g n e tic a lly f o r 2 h o u rs .
s o l u t i o n w as s t i r r e d
I c e w a t e r w as a d d e d ( 3 0 m l) a n d t h e
r e s u l t i n g s o l u t i o n w as e x t r a c t e d w i t h c h l o r o f o r m .
U pon e v a p o r a t i o n
o f t h e s o l v e n t 0 . 8 3 g ra m s ( 79%) o f a n o i l r e m a i n e d .
P r e p a r a t i o n o f 3 - b e n z y lb e n z o th ia z o liu m b ro m id e , 6 :
1 0 . 0 g ra m s ( ,OJk m o le s ) o f b e n z o t h i g z o l e w e re m ix e d w i t h
1 2 . 7 g ra m s ( .0 7 U m o le s ) o f b e n z y l b r o m id e i n 3 0 m l o f c h l o r o f o r m
and a llo w e d t o r e f l u x f o r 3 d a y s .
m i x t u r e w as f i l t e r e d
U pon c o o l i n g , t h e r e a c t i o n
an d w ash ed w ith c o ld a c e to n e ( 3 X 10 m l )
t o y i e l d 1 7 . 2 g ra m s ( 76%) o f a c o l o r l e s s . s o l i d ,
mp
1 8 3 -1 8 7 °C
P r e p a r a t i o n o f 0 - ( N - b e n z y l - N - f o r m y la m in o ) - t h i o p h e n o l , 1 2 :
6 . 0 g ra m s (
.0 2 m o le s ) o f 3 - b e n z y l b e n z o t h i a z o l i u m b r o m id e , 6 ,
w e re d i s s o l v e d i n 1 0 0 m l o f w a te r .
To t h i s
s tirre d
s o l u t i o n w as
a d d e d d r o p w i s e 30 m l o f ,a s a t u r a t e d s o d iu m b i c a r b o n a t e s o l u t i o n .
A f t e r f i n a l a d d i t i o n o f t h e s o d iu m b i c a r b o n a t e s o l u t i o n t h e r e ­
s u ltin g
s o lid .
s o l i d w a s. f i l t e r e d t o y i e l d IfvO g ra m s (82%) o f a c o l o r l e s s
•
mp
120°C
P r e p a r a t i o n o f 0- ( N - b e n z y l - N - f o r m y l a m i n o ) - t h i o a n i s o l e , ' 2 2 :
l f .0 g ra m s ( .0 1 6 3 m o le s ) o f o - ( N ^ b e n z y l - N - f o r m y l a m i n o ) - t h i o -
-
39-
p h e n o l ( 1 2 ) w e re m ix e d w i t h 1 0 0 m l o f
g ra m s (
s o d ira n h y d r o x i d e „
1 0 .0
.0 7 m o le s )• o f m e t h y l i o d i d e w e re a d d e d a n d t h e r e s u l t i n g
m ix tu r e w a s .m a g n e tic a lly s t i r r e d
o v e rn ig h t.
U pon . e x t r a c t i o n w i t h
c h l o r o f o r m , t h e r e r e m a i n e d 2 .9 g ra m s (69%) o f a n o i l .
P r e p a r a tio n o f 2 , 3 -d im e th y lb e n z o th ia z o liu m iq d id e ,
7-
7 . 3 g ra m s ( . OI4.9 m o le s ) o f 2 - m e t h y l b e n z o t h i a z p l e w e re m ix e d
w i t h 28 g ra m s ( - . 1 9 7 m o le s ) o f m e t h y l i o d i d e .
t u r e w as a l l o w e d t o r e f l u x o v e r n i g h t .
m i x t u r e w as f i l t e r e d
T he r e a c t i o n m ix ­
U pon c o o l i n g t h e r e a c t i o n
a n d t h e s o l i d w as w a s h e d w i t h c o l d a c e t o n e
( 3 X 1 0 m l ) and a llo w e d t o d r y i n a i r .
( 80%) o f a c o l o r l e s s s o l i d ,
mp
T h e r e r e m a i n e d 1 1 . 5 g ra m s
22 ^ - 225*0
P r e p a r a tio n o f o - ( M - m e th y l- N -a c e ty la m in o )-th io p h e n o l, 1 3 •
I.
5 . 0 g ra m s ( .0 1 7 2 m o le s ) o f 2 , 3 - d i m e t h y l b e n z o t h i a z o l i u m i o d i d e
( 7 ) w e re d i s s o l v e d i n lj.0 m l o f d i s t i l l e d w a t e r .
h y d ro x id e
( .0 6 2 m o le s ) w e re a d d e d a n d t h i s
t o s ta n d f o r I w eek.
£ 0 m l o f 5% s o d iu m
s o l u t i o n w as a llo w e d
T he r e a c t i o n m i x t u r e w as f i l t e r e d t o y i e l d
2 . 4 g ra m s ( 77%) o f a c o l o r l e s s s o l i d .
mp
1 7 9 -1 8 1 °C
A n a l y s i s f o r C gE^N O S « 2 / 3 H2 0
C a lc u la te d
C - 5 6 .0 % H -6 .U % N - 7 .3 % S - 1 6 .6 %
Found
0 -5 6 .1 8 % H -6 .1 0 % N -7 .1 7 % 6 -1 6 .5 4 %
-Ij1O 2.
o - ( N - m e t h y l - N - a c e t y l a m i n o ) - t h i o p h e n o l , 1 3 , w as a l s o p r e p a r e d
b y r e a c t i o n o f o -(N -m e th y la m in o )-th io p h e n o l w ith a c e t i c
a n h y d r id e .
T h e o - ( N - m e t h y l a m i h o ) ~ t h i o p h e n o l w as p r e p a r e d a s f o l l o w s :
O
g ra m s ( .0 3 m o le s ) o f 3 - m e t h y l - 2 - b e n z o t h i a z o l i n o n e w e re d i s s o l v e d
i n 16 m l o f h o t e t h a n o l .
T o t h i s w as a i d e d 7 . 1 g ra m s o f 85% e t h a n o l .
T h e r e a c t i o n m i x t u r e w as a l l o w e d t o r e f l u x f o r tw o h o u r s a n d t h e n
w as v a c u u m d i s t i l l e d t o y i e l d 3 « 0 g ra m s' (71% ) o f a c o l o r l e s s l i q u i d ,
bp
1 0 5 - 1 1 0 '0
1 ,0
(1U mm Hg)
g ra m (
.0072 m o le s ) o f o - ( N - m e th y la m in o ) - t h i o p h e n o l , a s
p r e p a r e d a b o v e , w as m ix e d w i t h 1 . 0 g rq m (
.0 0 9 8 m o le s ) o f a c e t i c
a n h y d r id e an d a llo w e d t o s t a n d f o r f i v e m in u te s .
The r e a c t i o n
m i x t u r e w as c o o l e d i n a n i c e b a t h a n d d i s t i l l e d w a t e r w as a d d e d .
T h e r e s u l t i n g s o l i d w as f i l t e r e d t o y i e l d 1 . 0 g ra m (77% ) o f a
c o lo rle s s s o lid .
mp
1 7 7 -1 7 8 °C
E q u a l a m o u n ts o f t h e o - ( N - m e t h y l - N - a c e t y l a m i n o ) - t h i o p h e n o l ,
1 3 , p r e p a r e d fr o m o - (N - m e th y la m in o ) - t h i o p h e n o l a n d f r o m 2 , 3 - d i m e t h y l b e n z o t h i a z o l i u m i o d i d e w e re m ix e d p u d a m e l t i n g p p i n t w as t a k e n o n
th e m ix tu re .
fro m b e n z o th ia z o liu m s a l t
179-181' C
fr o m t h i o p h e n o l
177-
178'C
m ix tu re
178-
179'G
P r e p a r a tio n o f o -( N -n ie th y l-M -a c e ty la m in o )-th io a x iis o le , 1 8 :
1 . 0 g r a m ■( .0 0 ^ 5 m o le s ) o f o - ( N - m e t h y l - N - a c e t y l a m i n o ) - t h i o p h e n o l , 13^ w as a d d e d t o 2 0 m l o f
s o d iu m h y d r o x i d e „
w as a d d e d u n t i l a l l t h e s o l i d d i s s o l v e d .
3 . 1 g ra m s (
E th a n o l
.0 2 2 m o le s )
o f m e t h y l i o d i d e w e r e a d d e d a n d t h e r e s u l t i n g s o l u t i o n w as s t i r r e d
m a g n e t i c a l l y f o r tw o h o u r s .
I c e w a t e r w as a d d e d ( 3 0 m l) a n d t h e
r e s u l t i n g p r e c i p i t a t e w as f i l t e r e d t o y i e l d 0 . 8 g ra m s ( 7h%) o f a
c o lo rle s s s o lid .
mp
8 0 -8 0 .3 ° 0
A n a ly s is f o r C ^K ^N O S
C a lc u la te d
C -6l.50% H -6 .71% N - ? .17%
Found
0 -6 0 .3 7 % H - 6 . 72% N - 7.01%
P r e p a r a t i o n o f 2 - m e t h y l - 3 - e t h y lb e n z o t h i a z o liu m i o d i d e ,
8:
l k '9 g ra m s ( . 1 m o le ) o f 2 - m e t h y l b e n z o t h i a z o l e w e r e m ix e d
w i t h 3 1 . 2 g ra m s ( .2 m o le s ) o f e t h y l i o d i d e .
t u r e w as a l l o w e d t o r e f l u x o v e r n i g h t .
m ix tu r e w as f i l t e r e d
a c e to n e
2 0 .0
T h e r e a c t i o n m ix ­
U pon c o o l i n g t h e r e a c t i o n
a n d t h e r e m a i n i n g s o l i d w as w a s h e d w i t h c o l d
( 3 X 10 m l ) and a llo w e d t o
d ry i n
g ra m s (63% ) o f a c o l o r l e s s s o l i d .
a ir.
mp
T h e p e r e m a in e d
1 8 6 -1 8 8 ” C (d )
P r e p a r a t i o n o f o - ( N - e t h y l - N - a c e t y l a m i n o ) - t h i o p h e n o l , l l j .:
3 . 0 g ra m s ( . 016 ^' m o le s ) o f 2 - m e t h y l - 3 - e t h y l b e n z o t h i a z o l i u m
io d id e ,
8 , w e re d i s s o l v e d i n 1*0 m l o f d i s t i l l e d w a t e r .
30 m l o f a
-Lt 2 -
%% s o d iu m h y d r o x i d e s o l u t i o n ( .0 6 2 m o le s ) w e re a d d e d a n d t h i s
s o l u t i o n w as - a llo w e d t o
s ta n d f o r I d ay .
T he r e a c t i o n m ix tu re
w as f i l t e r e d t o y i e l d 1 . 5 g ra m s ( h 7%) o f a c o l o r l e s s s o l i d ,
mp
1 0 0 -1 0 1 °C
A n a l y s i s f o r C ^ I l^ N O S
C a lc u la te d
Found
C - 6 l . £ l # H - 6 .6 ? ^ N - ? . , W
S - 1 6 .W
C- 6 1 . ?1 # H -6 ,1 C # N - ? . 09% S - 1 6 . 5 1 #
P re p a ra tio n o f o -(N -e th y l-N -a c e ty la m in o )-th io a n is o le , 1 9 :
1 . 0 g ra m ( .0 0 5 m o le s ) o f o - ( N - e t h y l - N - a c e t y l a m i n o ) - t h i o p h e n o l 3 IU 3 w as a d d e d t o 2 0 m l o f a 5% s o d iu m h y d r o x i d e s o l u t i o n .
E t h a n o l w as a d d e d u n t i l a l l t h e s o l i d w as d i s s o l v e d .
3 . 0 g ram s
( .0 2 1 m o le s ) o f m e t h y l i o d i d e w e re a d d e d a n d t h e r e s u l t i n g m ix ­
t u r e w as s t i r r e d m a g n e t i c a l l y f o r tw o h o u r s .
I c e w a t e r w as a d d e d
(3 0 m l) a n d t h e r e s u l t i n g s o l u t i o n w as e x t r a c t e d w i t h c h l o r o f o r m .
U pon e v a p o r a t i o n o f t h e s o l v e n t t h e r e r e m a i n e d 0 . ? g ra m s (65% )
o f an o i l .
P r e p a r a t i o n o f 2 - m e th y l- 3 - b e :n z y I b e n z o th ia z o liu m b ro m id e , 9 =
2 0 . 0 g ra m s ( .13U m o le s ) o f 2 - m e t h y l b e n z o t h i a z o l e w e re m ix e d
w i t h 2 3 . 0 g ra m s ( .13U m o le s ) - o f b e n z y l b r o m i d e .
m i x t u r e w as a l l o w e d t o r e f l u x f o r 5 5 h o u r s .
r e a c t i o n m i x t u r e w as f i l t e r e d
The r e a c t i o n
U pon c o o l i n g t h e
an d t h e re m a in in g s o l i d w ash ed w ith
-USc o ld a c e to n e
( 3 X 10 m l ) and a llo w e d t o
d ry in a i r .
e d 3 3 * 3 g ra m s ( 82%) o f a c o l o r l e s s s o l i d .
mp
T h e re re m a in ­
O lO eC
P r e p a r a tio n o f o -( N -b e n z y l-M -a c e ty la m in o )-th io p h e n o l, 1 3 =
3 - 0 g ra m s ( .0 1 3 6 m o le s ) o f 2 ~ m e t h y l ~ 3 - b e n z y l b e n z o t h i a z o liu m
b r o m i d e , 9S w e re d i s s o l v e d i n UO m l o f w a t e r .
h y d ro x id e s o l u t i o n
f o r one w eek.
SO m l o f $% so d iu m
( .0 6 2 m o le s ) w e re a d d e d a n d t h e m i x t u r e s t o o d
T h e r e s u l t i n g m i x t u r e w as e x t r a c t e d w i t h c h l o r o f o r m
a n d u p o n e v a p o r a t i o n o f t h e s o l v e n t t h e r e r e m a i n e d 0 . 2 0 g ra m s ($%>)
o f an o i l .
P re p a ra tio n o f th e
" m e th y le n e b a s e " fr o m 2 - m e t h y l - 3 - e t h y l b e n z o t h i a -
z o liu m i o d i d e :
3 .0
g ra m s ( . 0 1 m o le s ) o f 2 - m e t h y l - 3 - e t h y l b e n z o t h i a z o l i u m
i o d i d e , 8 , w e re d i s s o l v e d i n $0 m l o f d i s t i l l e d w a t e r .
10 ml o f
a 30 % s o d iu m h y d r o x i d e s o l u t i o n w e re a d d e d a l l a t o n c e ,
and th e
r e s u l t i n g p r e c i p i t a t e w as f i l t e r e d i m m e d i a t e l y .
" m e th y le n e
b a s e " w as q u i t e r e a c t i v e ,
a n u c l e a r m a g n e t i c r e s o n a n c e s p e c tr u m
w as t a k e n a s s o o n a s p o s s i b l e
nm r o f t h e
As t h e
a fte r f iltr a tio n .
" m e th y l e n e b a s e " i n CDCl^ ( d e l t a u n i t s
c e n te r e d a t 1 .2
a n d 1 .3 5
tw o t r i p l e t s
a d o u b l e t c e n t e r e d a t I . 75 tw o q u a r t e t s
c e n t e r e d a t 3 . 1 3 a n d 3 » 7 3 ; tw o s i n g l e t s
p ro to n s c e n te re d a t 6 .8 .
):
a t 2 . 6 a n d 1|..U3; a r o m a t ic
P re p a ra tio n o f th e
" m e th y le n e b a s e " f r o m 2 - m e t h y l - 3 - b e n z y l b e n z o -
th ia z o lin m b ro m id e :
3 .0
g ra m s ( .0 0 9 ^ m o le s ) o f 2 - m e t h y l - 3 - " b e n z y l b e n z o t h i a z o lin m
b r o m i d e , 9 , w e re d i s s o l v e d i n $0 m l o f d i s t i l l e d w a t e r „
a 5>0% s o d in m h y d r o x i d e s o l u t i o n w e re a d d e d a l l a t o n c e ,
s u l t i n g p r e c i p i t a t e w as f i l t e r e d i m m e d i a t e l y .
10 ml o f
and th e r e ­
A nm r s p e c t r u m w as
ru n as so o n a s p o s s ib le a f t e r f i l t r a t i o n .
nm r o f t h e
" m e th y le n e b a s e " i n CDCl^ ( d e l t a u n i t s
1 . 6 j a d o u b l e t c e n t e r e d a t In 3 J a s i n g l e t a t
).:
a s in g le t a t
a s in g le t a t
Ij..85$ a r o m a t i c p r o t o n s w e re a p p r o x i m a t e l y c e n t e r e d a t 7 . 0 .
REFERENCES
1.
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PART I I
SYNTHESIS OF I , I-DIM ETHYI--P, S-DIMETHYimEGYCLOPROPAKE
EROM DELTA-3-CAREME
-2 -
INTRODUCTI ON
T he b i c y c l i c m o n o te rp e n e ^ d e l t a - 3 - c a r e n e ,
o c c u rs f a i r l y f r e ­
q u e n t l y i n n a t u r e a s a c o n s t i t u t e n t o f a num ber o f t u r p e n t i n e o i l s .
It
o c c u rs la r g e ly i n th e
d e te c te d .
(+ )• fo r m b u t t h e
The s t r u c t u r e
(.-) fo r m h a s a l s o b e e n
o f th e u n s a tu r a te d h y d ro c a rb o n i s
g iv e n b e lo w .
h3
D . e l t a - 3 - c a r e n e w as f i r s t i s o l a t e d fr o m I n d i a n t u r p e n t i n e o i l
i n 1 9 2 0 b y S im o n s e n .
(
2 )'
D e s p ite th e e a r l y i s o l a t i o n
o f t h i s h y d ro ­
c a r b o n , d e l t a - 3 - c a r e n e h a d b e e n t h e s u b j e c t o f r e l a t i v e l y fe w
c h e m i c a l r e a c t i o n s u p t o t h e m id 1 9 6 0 's .
F o r e x a m p le , J . V e r g h e s e
re v ie w e d t h e c h e m is tr y o f d e l t a - 3 - c a r e n e i n 1 9 6 $ .
(3 )
T h i s w as
t h e f i r s t r e v ie w t h a t d e a l t s o l e l y w ith d e l t a - 3 - c a r e n e . tim e ,
S in c e t h a t
d e l t a - 3 - c a r e n e h a s b e e n t h e s u b j e c t o f a c o n s i d e r a b l e num­
b e r o f c h e m ic a l i n v e s t i g a t i o n s .
C o c k e r h a s r e c e n t l y r e v i e w e d som e
-3 -
o f th e s e in v e s tig a tio n s o f th e c h e m is try o f d e lta - 3 - c a r e n e .
I n i t i a l l y t h e r e w as d i f f i c u l t y p r e p a r i n g q u a n t i t i e s o f d e l t a - 3 c a re n e , how ever i f
is
now a v a i l a b l e i n l a r g e q u a n t i t i e s .
The s o le
know n s o u r c e o f d e l t a - 3 - c a r e n e i n t h e U n i t e d S t a t e s a n d C a n a d a
i s , i n th e b y -p ro d u c t tu r p e n tin e p ro d u c e d b y f iv e w e s te rn K ra ft
p u lp m i l l s .
CO
3 -c a re n e p e r day.
T h ese m ills p ro d u c e ab o u t 1000 g a llo n s o f d e l t a (3 )
D e l t a - 3 - c a r e n e c a n e x i s t i n tw o c o n f o r m a t i o n s , t h e b o a t fo r m
(la )
o r t h e i n v e r t e d b o a t fo rm ( l b ) ,
sh o w n b e l o w .
U pon i n i t i a l
FIGURE I — CONFORMATIONS OF DELTA-3- CARENE
o b s e r v a t i o n o f t h e s e fo r m s i t w o u ld a p p e a r t h a t f o r m l a i s m ore
c ro w d e d a n d h e n c e u n f a v o r a b l e . • H o w e v e r, A c h a r y a h a s sh o w n t h a t
t h e b o a t fo rm l a i s t h e p r e f e r r e d c o n f o rm a tio n . ^
T h e m a in p i e c e
o f e v i d e n c e f o r t h i s i s t h e nm r s p e c t r u m o f d e l t a - 3 - c a r e n e , w h ic h
sh o w s d i a m a g n e t i c s h i e l d i n g b y t h e d o u b l e b o n d o n t h e 8 -m e th y I
p r o t o n s . ( 0 .7 6 d e l t a
)
D e l t a - 3 - c a r e n e h a s f o u n d som e a p p l i c a t i o n i n t h e s y n t h e s i s
o f th e
a c i d i c c o m p o n e n ts c o n t a i n e d i n t h e n a t u r a l l y o c c u r i n g
(?)
in s e c tic id e
''P y r e t h r i n " .
b e lo w , a r e ,
c in e rin I
j a s m o lin I I
(2 d ), p y re th r in I
T h e s i x a c t i v e P y r e t h r i n s , show n
(2 a ), c in e rin I I
(2 e ),
(2 b ),
j a s m o lin I
and p y r e th r in I I
(2 c ),
(2 f).
^^
R i
R2
_2_
THE "PYRETHRINS"
( 2 a ) R1 =R2 =Me
( 2 d ) R1 = E t ; Rg= -COgMe
( 2 b ) R1 = M e; R p = -COgMe
( 2 e ) R1 = -CH=CH2 ; Rg= Me
( 2 c ) R1 = E t ; Rg= Me
( 2 f ) R1 = -CH=CH2 ; Rg= -CH=CHg
B ecause o f th e h ig h i n s e c t i c i d a l a c t i v i t y
o f th e P y r e th r in s , s y n th e tic ro u te s to
c h r y s a n th e m ic a c id ( 3 ) , h av e d e v e lo p e d .
a n d lo w m a m m alian t o x i c i t y
a key p a re n t a c id ,
^^
(+ ) t r a n s -
I n 1967 , M a t s u i a n d
-Ip c o w o rk e rs s y n th e s iz e d o p t i c a l l y p u re
( 3 ) fr o m ( + ) d e l t a - 3 - c a r e n e
(+ ) t r a n s - c h r y s a n th e m ic a c id
a s show n b e l o w .
A ls o , i n 1969,
SEVERAL
STEPS
COOH
CIS-CHRYSANTHEMIC
ACID
S a s a k i and c o w o rk e rs s y n t h e s iz e d c is -h o m o c h ry s a n th e m ic a c id ( W
fr o m d e l t a - 3 - c a r e n e
a s show n b e l o w .
Y
CHoCOOH
SEVERAL
ST E P S
D e lta -3 -c a re n e h a s a ls o b e e n u t i l i z e d i n th e s y n th e s is o f
d ip e n te n e
(3 )
and c a r v e s tr e n e
(6).
(l2 )
C om pounds 3 a n d 6 a r e
-6 -
1 7 0 -2 4 0
u s e f u l i n t h e m a n u f a c t u r e o f t e r p e n e r e s i n s f o r p e r f u m e s , c h e w in g
gums a n d p r e s s u r e s e n s i t i v e
a d h e s iv e s .
( 12)
H o w e v er , o t h e r t h a n
t h e s y n t h e s i s o f t h e c h r y s a n th e m ic a c i d s a n d p r o d u c t i o n o f d i p e n t e n e
(5 ) and c a rv e s tr e n e
( 6 ) , d e l t a - 3 - c a r e n e h a s fo u n d l i t t l e
a p p lic a tio n
i n c h e m ic a l s y n t h e s i s .
I n i t i a l l y , t h e d e l t a - 3 - c a r e n e p r o j e c t w as i n t e n d e d t o i n v o l v e
its
s te p - w is e d e g r a d a tio n , lo o k in g c a r e f u l l y a t th e s te r e o c h e m is tr y
o f th e p ro d u c ts .
T h e re a p p e a re d t o b e a m b ig u ity i n t h e c o n f ig u r a -
t i o n a l a s s i g n m e n t s f o r som e o f t h e s e d e g r a d a t i o n p r o d u c t s .
( I S—1 7 )
H o w e v er , i n 1 9 6 ? t h e s e a m b i g u i t i e s w e re r e s o l v e d , m a i n l y b y
K ro p p
and o th e r w o rk e rs .
T h e n i t w as d e c i d e d t o
2 l)
a tte m p t th e s y n th e s is o f th e h ig h ly
s t r a i n e d h y d ro c a rb o n I , l- d i m e t h y l - 2 , 3 -d im e th y le n e c y c lo p ro p a n e ( ? ) .
-7 -
SEVERAL
STEPS
A t t h e b e g i n n i n g o f t h e p r o j e c t , t h e p a r e n t co m p o n n d , I , 2 - d i m e th y le n e c y c lo p r o p a n e , h a d n o t b e e n s y n t h e s i z e d , b u t s e v e r a l d e r i v - '
a tiv e s
o f I , 2 - d i m e t h y l e n e c y c l o p r o p a n e ( 9 ) w e re know n a n d h a d a t -
t r a c t e d c o n s id e ra b le i n t e r e s t .
(
2 2 —2 6 I
T h e s e d im e th y le n e c y c lo p r o ­
p a n e s a r e h i g h l y s t r a i n e d a s tw o o f t h e c a r b o n s i n t h e c y c lo p r o p a n e
rin g
are sp
2
in an a lk e n e .
60 d e g r e e s ,
h y b r i d i z e d , w h ic h m ean s a n o r m a l a n g l e o f 1 2 0 d e g r e e s
H ow ever t h e a n g le s i n
an e q u i l a t e r a l t r i a n g l e
are
T h e r e f o r e t h e s e s y s te m s c o u ld b e v e r y r e a c t i v e b e c a u s e
o f t h i s h ig h d e g re e o f a n g le s t r a i n .
R e c e n t l y t h e p a r e n t com pound
w as s y n t h e s i z e d b y B l o c h , L e P e r c h e c a n d C o n i a , b y h e a t i n g v i n y l i d e n e
c y c lo p ro p a n e (8 ) t o
g i v e 1 , 2 - d i m e t h y l e n e c y c l o p r o p a n e ;(_9) i n 3Q&
y i e l d a s sh o w n b e l o w .
(27)
T h e y r e p o r t e d t h e m a ss s p e c t r u m , t h e
i n f r a r e d s p e c tr u m , t h e u l t r a v i o l e t s p e c tru m an d t h e n u c l e a r m a g n e tic ,
r e s o n a n c e s p e c tr u m o f t h i s h i g h l y v o l a t i l e
b u t th e y d id n o t p re p a re a d e r iv a tiv e
and u n s ta b le s p e c ie s ,
o f I , 2 -d im e th y le n e c y c lo p ro -
-8 -
320°
3 MIN
>
+ 8_ + POLYMERS
s^CH2
8
9
p an e (j? ).
T h e a b o v e m e th o d h a s b e e n u s e d b e f o r e t o p r e p a r e s u b s t i t u t e d
d i m e t h y l e n e c y c l o p r o p a n e s , a s sh o w n b e l o w .
(2 6 ,2 8 )
15%
-9 -
A l s o , i n 1 9 9 9 ? B l o in q u i s t a n d L o n g o n e p r e p a r e d p r e c u r s o r s f o r
t h e p r e p a r a t i o n o f d im e th y le n e c y c lo p ro p a n e and tr i m e t h y l e n e c y c l o ­
p ro p a n e .
T h e com p o u n d s t h e y p r e p a r e d a r e show n b e l o w , a n d
CH^N(CHnj)£>
CH2 N(CH3 ) 2
t r a n s - 1 , 2 - b i s -(DIMET H IL AMINOMETHYL )-C YCLOPROPANE
s h o u ld e a s i l y g iv e th e
H2 N(CH3)2
^ C H 2 N(CH3)2
t r a n s - 2 , 3 - b i s -(DIMET HYLAHNOMETHIL ) -I-M ET HILENECICLOPROP ANE
am in e o x i d e o r t h e q u a t e r n a r y a m in e , w h ic h
s h o u ld g iv e d im e th y le n e c y c lo p ro p a n e o r tr im e th y le n e c y c lo p r o p a n e
upon p y r o ly s is .
T he t r a n s - 1 , 2 - b i s - ( d im e th y la m in o m e th y l)- c y c l o ­
p r o p a n e w as p r e p a r e d fr o m t r a n s - 1 , 2 - c y c l o p r o p a n e d i c a r b o x y l i c a c i d
an d t h e t r a n s - 1 , 2- b i s - ( d im e th y la m in o m e th y l)- l- m e th y le n e c y c lo p r o p a n e
w as p r e p a r e d f r o m F e i s t ' s
a c id ( t r a n s - 1 -m e th y le n e c y c lo p ro p a n e -
-1 0 -
2 ,3 -d ic a rb o x y lic
a c id ) .
H o w e v e r, t h e
a u th o rs d id n o t r e p o r t th e
s y n t h e s i s o f e i t h e r o f t h e n o v e l c o m p o u n d s, d i m e t h y l e n e c y c l o p r o p a n e
o r trim e th y le n e c y c lo p ro p a n e .
I n 1 9 6 5 a n d 1 9 6 6 , tw o l a b o r a t o r i e s i n d e p e n d e n t l y r e p o r t e d
th e s y n th e s is o f trim e th y le n e c y c lo p ro p a n e .
(3 0 ,3 1
D o rkco
o s y nn th
th e ­
s i z e d tr im e th y le n e c y c lo p r o p a n e i n t h e f o llo w in g m an n er:
h
2
c
= < ^
/COOH
LlAIHa ^ O H 9 .
ETHER ^ H2 O
CH2 OH
H2C = < \
^ C H 2 OH
^C O O H
PBr-,
PYRIDINE
(3 0 ,3 2 )
^C H 2
/ C H 2 Br
KOH
^ H2C -'
150°
^
H2C = < ]
^ C H 2 Br
x CH2
T h e co m pound w as c h a r a c t e r i z e d b y i t s m a ss s p e c t r u m , i n f r a r e d
s p e c tr u m , n u c l e a r m a g n e tic r e s o n a n c e s p e c tru m an d u l t r a v i o l e t
s p e c tr u m .
W a itk u s a n d c o w o r k e r s s y n t h e s i z e d t h e h y d r o c a r b o n i n tw o w ays
a s sh o w n b e l o w . KS> ’
T hey a ls o c a ta l y ti c a l l y re d u c e d th e u n -
-1 1 -
CH2 N(CH3 )3 , OH®
e
OH
(H3C)3NH2C
CH2 N(CH3 )3 ,OH9
s a t u r a t e d h y d ro c a rb o n t o c i s - 1 , 2 , 3 -tr± m e th y lc y c lo p ro p a n e , p r o v id ­
i n g m o re c o r r o b o r a t i v e c h e m i c a l e v i d e n c e .
-1 2 -
RESULTS
and d is c u s s io n
I n sch e m e I t h e s t e p s i n t h e s y n t h e s i s o f I , l - d i m e t h y l - 2 , 3 d im e th y le n e c y c lo p ro p a n e ( ? ) ,
show n.
I t is
c a re n e ( l )
s t a r t i n g fro m d e lta - 3 ~ c a r e n e ( l )
are
o f im p o rta n c e t h a t t h e r e a c t i o n s r u n on d e l t a - 3 -
a n d t h e coirrpounds t h e r e b y d e r i v e d d o n o t b r e a k t h e t h r e e
m em b ered r i n g .
T h e r e w e re tw o p o s s i b l e r o u t e s t o t h e com pound 3., 3 - d i m e t h y l 2 - ( 2 - o x o p r o p y l) e y e l o p r o p y l a c e t a ld e h y d e ( l 3 ) , r e f e r r e d t o
k e to -a ld e h y d e .
c a re n e ,
T h e se w e re : l )
as th e
th r o u g h t h e e p o x id e o f d e l t a - 3 -
o r 2) th ro u g h d i r e c t o z o n o ly s is o f d e l t a - 3 - c a r e n e w ith a
r e d u c t i v e w o rk u p o f t h e o z o n i d e .
T h e f i r s t m e th o d w i l l now b e
d is c u s s e d .
T h e r e w e re tw o p o s s i b l e e p o x i d e s t h a t c o u l d b e f o r m e d fro m
d e l t a - 3 - c a r e n e , «c-3, I i - e p o x y c a r a n e a n d ^ )- 3 , L - e p o x y c a r a n e .
I n th e
p a s t t h e r e h a d b e e n d i s a g r e e m e n t c o n c e r n i n g w h ic h nam e h a d w h ic h
s tru c tu re .
A rb u z o v a n d c o w o r k e r s c o n c l u d e d fr o m t h e n u c l e a r
m a g n e t i c r e s o n a n c e s p e c t r a o f t h e e p o x i d e s t h a t t h e e c -e p o x id e h a d
t h e c y c lo p r o p a n e r i n g
and t h e e p o x id e r i n g c i s t o
O th e r w o rk e rs h a d g iv e n t h e o p p o s ite a s s ig n m e n t.
a n d 1 9 6 7 K ro p p
(l8 )
one a n o th e r .
(
21)
I n 1966
(2 l)
^ a n d B row n a n d S u z u k i ^
p ro d u c e d f u r th e r
e v id e n c e f o r t h e l a t t e r a s s ig n m e n t an d i t
i s now a c c e p t e d t h a t
SCHEME I - SYNTHESIS OF l,l-DIMETHYl-2,3-DIMETHYLEMECYCLOPROPAME
(DCOOOH
NaBlO
NaOBr
OOH
OOH
CURT IUS
REACTION
5 % Pd on C
-!li­
t h e o c - 3 ,ll- e p o x y c a r a n e h a d t h e s t r u c t u r e 1 0 , i . e . w i t h t h e c y c l o ­
p ro p a n e r i n g t r a n s t o t h e e p o x id e r i n g ,
th e s tr u c tu r e 11.
a n d ^ ~ 3 ,U - e p o x y c a r a n e h a d
F u rth e r p ro o f f o r t h i s
a s s i g n m e n t cam e w hen
S u z u k i a n d c o w o r k e r s sh o w ed t h a t t h e m a j o r p r o d u c t s f r o m t h e h y d r o ­
g e n a t i o n o f t h e cc- a n d p - e p o x y c a r a n e w e re i s o c a r a n o l a n d n e o c a ranol re s p e c tiv e ly .
(1 9 )
T h o se s t r u c t u r e s
a r e show n b e l o w .
It
NEO-CARANOL
ISOC ARANOL
h a d b e e n e s t a b l i s h e d t h a t w hen R a n e y n i c k e l w as u s e d a s a c a t a l y s t ,
t h e r e w o u ld b e r e t e n t i o n o f c o n f i g u r a t i o n o f t h e e p o x i d e .
(1 9 )
I n a d d i t i o n A rb u z o v a n d c o w o r k e r s r e c e n t l y r e v e r s e d t h e i r i n i t i a l
a s s i g n m e n t s o f cc- a n d ^ - e p o x y c a r a n e .
In
(35>)
o r d e r t o e x p l a i n t h e n u c l e a r m a g n e tic re s o n a n c e s p e c t r a
o f t h e tw o d i f f e r e n t e p o x i d e s o f d e l t a - 3 - c a r e n e . B row n s u g g e s t e d
th a t th e
a n is o tro p ic d is tr ib u tio n
o f a n e p o x i d e r i n g w o u ld b e p a r a ­
m a g n e tic a ro u n d t h e oxy g en and d ia m a g n e tic a t th e n e ig h b o r in g c a rb o n
a to m s .
(2 l)
T h i s h a s b e e n sh o w n t o b e t h e
case in
e x p la in in g th e
-1 5 -
n u c l e a r m a g n e tic re s o n a n c e s p e c t r a o f o t h e r e p o x id e s .
W hen d e l t a - 3 - c a r e n e
( l ) w as r e a c t e d w i t h p e r b e n z o i c a c i d ,
OC- 3 , U - e p o x y c a r a n e ( l O ) r e s u l t e d .
i f one r e f e r r e d t o f ig u r e I
o f d e lta -3 -c a re n e
(la ).
( ^ ,2 l)
^ h i s w as p r e d i c t a b l e
and o b s e rv e d th e p r e f e r r e d c o n fo rm a tio n
T h e b o t t o m s i d e o f t h e m o l e c u l e w as o p e n
f o r a t t a c k , w h e r e a s t h e t o p s i d e w as h i n d e r e d , p r i m a r i l y b y t h e
8 -m e th y l g ro u p .
O nce t h e e p o x i d e w as f o r m e d , t h e r e w e re tw o c o n ­
f o r m a t i o n s i n w h ic h i t
c o u l d e x i s t a s show n b e l o w .
A rb u z o v and
CONFORMATIONS OF c c - 3 ,L-EPOXYCARANE
c o w o r k e r s h a v e s t a t e d t h a t t h e m o l e c u l e s o f oc-3, L - e p o x y c a r a n e e x i s t e d e q u a l l y i n t h e s e tw o c o n f o r m a t i o n s .
s u lts
(3 5 )
T hey b a se d t h e i r r e ­
o n t h e t e m p e r a t u r e d e p e n d e n c e o f t h e PMR s p e c t r u m o f a : - 3 , L -
e p o x y c a ra n e .
A c id h y d r o l y s i s o f c c - 3 ,L - e p o x y c a r a n e r e s u l t e d i n
a tra n s d io l
- 16 -
p r e d i e t e d a s e p o x id e s o f c y c lic
o l e f i n s n o rm a lly o pen w ith i n ­
v e r s io n o f c o n f ig u r a tio n a t th e m o st h ig h ly s u b s t i t u t e d c a rb o n
ZQZ X
o f t h e e p o x id e r i n g . ^
T he ^ -3 ,U -e p o x y c a r a n e ( l l )
c o u l d b e s y n t h e s i z e d i n tw o w a y s.
T h e f i r s t m e th o d i n v o l v e d t h e c o n v e r s i o n o f t h e g l y c o l ( l U ) t o
its
m o n o to s y la te and t h e n i t s
a s sh o w n b e l o w .
th is
r e a c t i o n w ith b a s e t o t h e ^ -e p o x id e
T h e s e c o n d m e th o d , a n d t h e m e th o d u s e d i n
l a b o r a t o r y , in v o lv e d th e r e a c t i o n o f d e l t a - 3 - c a r e n e w ith N-
b r o m o s u c u c c i n i m i d e (NBS) i n
h y d rin .
(3 7 )
T re a tm e n t o f t h e b ro m o h y d rin w ith p o ta s s iu m t - b u t o x i d e
gave ^ - 3 , U -e p o x y c a ra n e ( l l )
w as f o r m e d i t
tio n s .
a q u e o u s d i o x a n e t o p r o d u c e t h e b ro m o -
c o u ld a ls o ,
a s sh o w n b e l o w .
O nce t h e ^ - e p o x i d e
a s t h e o c - e p o x id e , e x i s t i n tw o c o n f o rm a ­
T h e s e tw o c o n f o r m a t i o n s a r e show n b e lo w a n d A rb u z o v a n d
c o w o rk e rs h av e s t a t e d t h a t t h e m o le c u le s o f jl- 3 ,b - e p o x y c a r a n e
-1 7 -
PYRIDINE
Aq. DIOXANE
Il
-1 8 -
CONFCRmTIONS OF ^ - 3 , U-EPOXICARANE
e x i s t e d 75% o f t h e t i m e i n c o n f o r m a t i o n ( l l a ) a n d 2$% i n
R e a c tio n o f ^ -3 ,U - e p o x y c a r a n e ( l l )
a s c a n b e s e e n i n sch e m e I .
w ith d i l u t e
(l i b ) .
a c id a ls o gave d io ls
T h is r e a c t i o n a p p e a re d t o b e s lo w e r
t h a n t h e a c i d h y d r o l y s i s o f <c-3} U - e p o x y c a r a n e ( 1 0 ) a n d h a s b e e n
sh o w n t o g i v e tw o d i o l s , com p o u n d s 1 2 a n d 1 3 .
The r e a c tio n
w as c a r r i e d o u t i n t h i s l a b o r a t o r y , b u t t h e p r o d u c t s w e r e n o t
c h a ra c te riz e d .
R e a c t i o n o f t h e d i o l lU , 3?, U < t - c a r a n e d i o l , w i t h s o d iu m b i s ­
m u th a t e (N aB iO ^) r e s u l t e d i n c l e a v a g e o f a c a r b o n - c a r b o n s i n g l e
bond and gave th e k e to -a ld e h y d e ( l £ )
a s show n b e l o w .
T h is r e a c tio n
g a v e q u i t e h i g h y i e l d s w h en s m a l l a m o u n ts o f m a t e r i a l w e re u s e d .
H o w e v e r, w h en l a r g e r q u a n t i t i e s o f m a t e r i a l w e re u s e d t h e y i e l d s
w e re d r a s t i c a l l y r e d u c e d .
T h i s m e th o d o f s y n t h e s i z i n g t h e k e t o -
-1 9 -
OH
N aB I
-------------- —
—
kH
OH
H
^
>
---------------
15
14
a l d e h y d e w as a b a n d o n e d i n f a v o r o f o z o n o l y s i s o f d e l t a - 3 - c a r e n e .
The se c o n d r o u te t o th e k e to - a ld e h y d e
o f d e lta -3 -c a re n e .
( l ^ ) in v o lv e d o z o n o ly s is
A c t u a l l y , r e d u c t i v e w o rk u p o f t h e
y ie ld e d th e k e to -a ld e h y d e
ed th e k e to -a c id ( l 6 ) .
( l 5 ) w h e r e a s o x i d a t i v e w o rk u p h a s y i e l d ­
D e lta -3 -c a re n e h as b ee n s u b je c te d to
n o l y s i s s e v e r a l tim e s , b e g in n in g i n 1927• ^ ^
p ro c e e d in g w ith th e
o z o n id e h a s
7 ,1 0 ,1 1 )
ozo­
Be f o r e
o z o n o ly s is o f d e lta - 3 - c a r e n e , th e p ro c e s s o f
o z o n o ly s is s h o u ld b e d is c u s s e d .
T h e m o s t r e c e n t r e v i e w o f o r g a n i c o z o n e c h e m i s t r y w as g i v e n
by B a ile y in 1958.
^
S in c e t h a t tim e t h e r e h av e b e e n s e v e r a l
p a p e r s t h a t h a v e come o u t o n t h e m e c h a n is m o f o z o n o l y s i s .
(th is l i s t
o f re fe re n c e s is
n o t in c lu s iv e )
r e v i e w e d t h e m e c h a n is m s o f o z o n o l y s i s .
on t h e
^
^
R e c e n t l y , M u rra y h a s
(^ ,1 * 8 )
New i n f o r m a t i o n
o z o n o ly s is r e a c tio n h a s in d ic a te d t h a t th e r e a c tio n has
p r o b a b l y p r o c e e d e d b y s e v e r a l d i f f e r e n t p a th w a y s d e p e n d in g u p o n
-2 0 a num ber o f r e a c t i o n c o n d i t i o n s .
I t h a d b e e n w e l l a c c e p t e d t h a t a p r i m a r y o z o n i d e w as fo rm e d
b e f o r e t h e n o rm a l o z o n id e .
H o w ev er t h e s t r u c t u r e
o f t h i s p rim a ry
o z o n i d e h a s b e e n i n q u e s t i o n a n d t h e tw o s t r u c t u r e s show n b e lo w
A
I
h av e b e e n d e b a te d .
S t r u c t u r e I w o u ld r e s u l t f r o m t h e 1 , 3 - c y c l o ­
a d d i t i o n o f o z o n e t o t h e d o u b l e b o n d ; w h e r e a s s t r u c t u r e I I w o u ld
r e s u l t fr o m I , 2 - c y c l o a d d i t i o n .
One p i e c e o f e v i d e n c e t h a t h a s
a p p e a r e d i n f a v o r o f s t r u c t u r e I w a s t h e lo w t e m p e r a t u r e nm r s p e c ­
t r u m o f t h e p r i m a r y o z o n i d e o f t r a n s - d i - t - b u t y l e t h y l e n e w h ic h i n d i c a t e d t h a t b o t h m e t h i n e p r o t o n s w e re e q u i v a l e n t . ( 5 $ )
o th e r r e c e n t d a ta a p p e a re d to be i n fa v o r o f s tr u c tu r e I I
H ow ever
( 5 1 ,5 2 )
T h e m o s t c o m p l e t e a n d m o s t w i d e l y a c c e p t e d m e c h a n is m f o r t h e
o z o n o l y s i s r e a c t i o n w as b y C r i e g e e a s show n b e l o w .
m e c h a n is m h a s b e e n u s e d i n e x p l a i n i n g m o s t o f t h e
p e rim e n ta l d a ta
(W
(U6)
T h is
a c c u m u la te d e x -
B ut r e c e n t e x p e rim e n ta l d a ta c o u ld n o t be
e x p l a i n e d b y t h e C r i e g e e m e c h a n ism
(51-5U)
T h e re fo re m o d ific a -
-2 1 -
R\ _
/ R
z C - Y O3- ^
R\ Ax / R
cv
RZ
xR
■>)c -o +
&
REACTIVE
SOLVENTS
1
,0 A
Vw
Z
xR
CRIEGEE
tio n s
of i t
h ere to
h av e b e e n m ade.
V
ck h *
m e c h a n is m
H o w e v e r, i t i s
o n ly im p o rta n t
s t a t e t h a t th e c o u rse o f o z o n o ly s is h as b e e n a f f e c te d b y
o l e f i n g e o m e try ,
tra tio n ,
or
s te ric
f a c t o r s , te m p e r a tu r e , s o l v e n t and c o n c e n ­
a n d t h a t t h e C r i e g e e m e c h a n is m n e e d s t o b e m o d i f i e d . ^ ^
I n 1 9 6 1 Y -R . N a v es a n d A -V . G r a m p o lo f f
s y n th e s iz e d c i s -
-2 2 c a ro n ic
a c i d f r o m d e l t a - 3 - c a r e n e , r e p e a t i n g t h e w o rk o f S em m ler
and v . S c h i l le r
(3 9 )
, a s show n b e lo w .
T h e i r i n t e r m e d i a t e com pound
KMnQ
COOH
COOH
KMnO4
COOH
COOH
KMnQ
(I? ),
I , l- d im e th y lc y c lo p r o p a n e - c is - 2 ,3 - d ia c e tic a c id , r e f e r r e d to
a s t h e d i a c i d , w as n e e d e d i n t h e s y n t h e s i s o f 7 , 1 , 1 - d i m e t h y l - 2 , 3 d im e th y le n e c y c lo p ro p a n e .
H o w ev er t r o u b l e
aro se i n u s in g t h e i r
e x p e r i m e n t a l p r o c e d u r e s f o r t h e w o rk u p o f t h e o z o n i d e s b e c a u s e
t h e p r o d u c t s o b t a i n e d w e re n e v e r p u r e , e v e n a f t e r r e p e a t e d d i s t i l ­
la tio n s .
T h e r e f o r e s e v e r a l d i f f e r e n t m e th o d s w e re e m p lo y e d t o
-
23-
w o rk u p t h e o z d n i d .e s . A .sum m ary o f th e m i s
g iv e n i n T a b le I .
TABLE I - OZPMOLYSIS OF DELTA-3-CAREEE
_C
S o lv e n t
M e th o d o f w o rk u p
P ro d u ct
■R e f .
I . A c e tic a c id
0
Z in c a n d A c e t i c a c i d
k e to -a ld e h y d e
3 9 ,1 0
2 . A c e tic a c id (5 $ )
0
H y d ro g e n p e r o x i d e
k e to -a c id
3 9 ,b 0
3 . E th y la c e ta te
0
Jones re a g e n t
k e to -a c id
36
D im e th y l s u l f i d e
k e to -a ld e h y d e
11,37
u . M e th a n o l
-7 8
3 . M e th a n o l
0
' no p ro d u c t
o b ta in e d
F o r m ic a c i d / H^Og
38
E v e r y m e th o d a t t e m p t e d t o w o rk u p t h e o z o n i d e s g a v e im p u r e p r o d u c t s .
T h e m e th o d o f c h o i c e se e m e d t o b e n u m b e r it i n T a b l e I ,
T h i s w o rk u p
o f t h e o z o n i d e a t lo w t e m p e r a t u r e w i t h d i m e t h y l s u l f i d e g a v e t h e
k e to -a ld e h y d e i n th e p u r e s t fo rm .
in
H o w e v e r5 o z o n o l y s i s o f a l k e n e s
a p r o t i c . s o l v e n t s u c h a s m e t h a n o l d i d n o t g i v e t h e n o r m a l o z o n i d e , .. .
I n s t e a d i t p r o d u c e d a m e th o x y h y d r o p e r o x i d e .
(L 2 )
I n th e case o f
t h e o z o n o l y s i s o f c y c lo h e x e n e i n m e t h a n o l a m i x t u r e o f p o l y m e r i c
p e r o x i d e s w e re f o r m e d a s show n b e l o w ,
F o rm A w o u ld b e t h e m a j o r
p r o d u c t i f t h e s o l v e n t w e re re m o v e d i m m e d i a t e l y .
I f th e m a te ria l
w e re a l l o w e d t o r e m a i n i n m e t h a n o l , t h e n fo r m B w o u ld b e t h e m a j o r
p e ro x id e .
P a p p a s a n d K e a v e n e y h a v e show n t h a t t h e s e p o l y m e r i c
p e r o x i d e s w e re r e d u c e d b y d i m e t h y l s u l f i d e
a t lo w t e m p e r a t u r e t o
-2h-
O
OCH3
H - C - (C
H
OCH3
0 - 0 - CH-C—(C
H
H
OCH3
C-( C H ^ - C-O OH
OH
H
OH
H
OCH3
Y
OGH3
A
OCH3
OCH3
^
H-CHC H ^ 4 - C-O-O-H C—fC H ^ ^ O -O -O K C- (CH ^ ) ^ C- O O H
OCH3
H
OCH3
H
OCH3
H
B
th e c o rre s p o n d in g a ld e h y d e s .
( 57)
Two o t h e r m e th o d s w e re a t t e m p t e d t o
a ld e h y d e ( l £ )
a s sh o w n b e lo w .
s y n th e s iz e th e k e to -
O x id a tio n o f d e l t a - 3 - c a r e n e w ith
P
+
(P)5 SiO-^r-OSr((I))3
15
-25>-
HlO4-KMnO4
15
O nce t h e k o t o - a l d e h y d e w as o b t a i n e d ,
it
c o u ld th e n be c o n v e r t-
e d t o t h e k e t o - a c i d ( l 6 ) b y r e a c t i o n w i t h p o t a s s i u m p e r m a n g a n a te
i n a c e t o n e a t 0 °C .
S a s a k i and c o w o rk e rs
h ave c la im e d t h a t
t h e y o b t a i n e d p u r e k e t o - a c i d b y t h i s m e th o d ( i . e . , f i r s t r e d u c ­
tio n
o f th e o s o n o ly s is p ro d u c t w ith d im e th y l s u l f i d e ,
t h a t p r o d u c t r e a c t e d w i t h p o t a s s i u m p e r m a n g a n a te ) .
w hen t h e i r e x a c t p r o c e d u r e w as f o l l o w e d ,
ed as th e k e to - a c id .
and th e n
H o w e v e r,
a l i g h t b ro w n o i l r e s u l t ­
A p u r e s a m p le o f t h e k e t o - a c i d w as n e v e r
o b ta in e d .
T he n e x t s t e p i n t h e s y n t h e s i s r e q u i r e d th e k e t o - a c i d t o be
o x id iz e d t o th e s y m m e tric a l d i a c i d
o x i d a t i o n o f a m e th y l k e to n e t o
r e a c t i o n a s show n b e lo w .
(1 7 ).
T h e e a s i e s t m e th o d f o r
a n a c i d w as b y u s e o f t h e h a l o f o r m
T h a t t h e s t r u c t u r e w as s t i l l
c i s w as
-2 6 -
COOH
COOH
i n d i c a t e d b y t h e n u c l e a r m a g n e t i c r e s o n a n c e s p e c tr u m o f t h e d i a c i d
i n w h ic h t h e gem d i m e t h y l p r o t o n s w e re n o t a s i n g l e t , b u t w e re
s p lit.
I f t h e s t r u c t u r e w e re t r a n s , t h e n o n e w o u ld e x p e c t t h e gem
d im e th y l p r o to n s t o b e e q u i v a l e n t .
w e re n e v e r v e r y h i g h , b u t t h i s
The y ie ld s
of th is
re a c tio n
c o u ld h av e b e e n a r e s u l t o f th e
im p u re s t a r t i n g m a t e r i a l .
Up t o t h i s p o i n t t h e y i e l d s
o f t h e r e a c t i o n s w e re v e r y p o o r .
B ut p o o r y ie ld s can be t o l e r a te d i f
on c a n o b t a i n p u r e s a m p l e s .
H o w ev er t h i s w as n o t t h e c a s e w i t h t h e k e t o - a c i d ( l 6 ) .
d is tilla tio n s ,
d e c o l o r i z i n g c h a r c o a l o r c h r o m a to g r a p h y w o u ld n o t
g i v e a p u r e co m p o u n d .
a t th e l e a s t .
w as a s o l i d ,
R e p e a te d
T h e r e a lw a y s r e m a i n e d a l i g h t b ro w n c o l o r ■
The d ia c id
and i t
( l ? ) d e r i v e d fr o m t h e k e t o - a c i d , h o w e v e r,
i n t u r n c o u ld b e r e c r y s t a l l i z e d t o
g iv e a p u re
co m p o u n d .
The d ia c id
( l ? ) w as t h e n c o n v e r t e d t o t h e d ia m in e
(1 8 ), 1 ,1 -
-2 7 -
d i m e t h y l - c i s - 2 , 3 - b i s - ( a m iin o m e th y l)- c y c l o p r o p a n e d i h y d r o c h l o r i d e
v i a a " d o u b le b a r r e l e d " S c h m id t t y p e r e a c t i o n .
I t w o u ld h a v e b e e n
i m p r a c t i c a l t o u s e t h e S c h m id t r e a c t i o n i t s e l f ,
as th e c o n c e n tra te d
s u lfu ric
a c i d r e q u i r e d w o u ld o p e n t h e t h r e e m em bered r i n g .
H ow ever
a m o d i f i e d C u r t i u s r e a c t i o n w as f o u n d i n w h ic h c i s - 2 - p h e n y l c y c l o p r o p y l am in e w as p r e p a r e d i n
77% y i e l d fr o m c i s - 2 - p h e n y l c y c l o p r o -
pane c a r b o x y lic a c id .
A s c a n b e s e e n b e lo w , t h e m e th o d i n -
' ’
0
D NE% , o*
' V 7 x^ /
H
17
C0 0 H
a Cl CO2 Etl 0"
^
0
S-O-C-OEt
-
28-
v o lv e d h e a tin g an a c id a z id e t o c a u s e l o s s
tio n
o f an is o c y a n a te .
o f n i t r o g e n an d fo rm a­
T h i s i s o c y a n a t e w as t h e n h y d r o l y z e d w i t h
20% h y d r o c h l o r i c a c i d t o g i v e t h e r e s u l t i n g am in e h y d r o c h l o r i d e „
When t h i s r e a c t i o n w as u s e d o n t h e d i a c i d
( 1 7 ) , t h e d ia m in e h y d r o ­
c h lo rid e
T h a t th e c i s
( l 8 ) w as o b t a i n e d i n 66% y i e l d .
s tru c tu re
r e m a i n e d was. a g a i n i n d i c a t e d b y t h e n u c l e a r m a g n e t i c r e s o n a n c e
s p e c t r u m i n w h ic h t h e gem d i m e t h y l p r o t o n s w e r e n o t a s i n g l e t ,
as
w o u ld h a v e b e e n e x p e c t e d f o r t h e t r a n s co m p o u n d .
E x h a u s tiv e m e t h y l a t i o n o f t h e d ia m in e h y d r o c h lo r id e
m e t h y l i o d i d e g a v e t h e d i q u a t e r n a r y ammonium i o d i d e
(19),
( l 8 ) w ith
l^ l-d i-
m e t h y l - c i s - 2 , 3 - b i s - ( d i m e t h y la m in o m e th y l ) - c y c l o p r o p a n e d i m e t h o i o d i d e ,
i n 90% y i e l d .
by i t s
T h a t t h e q u a t e r n a r y s a l t w as f o r m e d w as i n d i c a t e d
n u c l e a r m a g n e t i c r e s o n a n c e s p e c t r u m w h ic h g a v e a
ra tio
of
3 t o I f o r t h e m e th y l g ro u p s on t h e n i t r p g e n t o th e . m e th y l g ro u p s
on th e c y c lo p r o p a n e „
A ls o t h e r e w e re tw o s i n g l e t s f o r t h e gem
d i m e t h y l p r o t o n s , w h ic h i n d i c a t e d a c i s s t r u c t u r e .
e d t h e q u a t e r n a r y ammonium i o d i d e
H a v in g p r e p a r ­
( 1 9 ) , t h e n e x t s t e p w as t h e
H ofm ann e l i m i n a t i o n r e a c t i o n t o p r o d u c e t h e d i m e t h y le n e com pound.
I n i 960 C ope a n d T r u m b u ll r e v i e w e d t h e H ofm ann e l i m i n a t i o n
r e a c t i o n a n d t h e a m in e o x id e p y r o l y s i s .
'
^
T h e H ofm ann e l i m i n a ­
t i o n r e a c t i o n i n v o l v e d t h e d e c o m p o s i t i o n o f a q u a t e r n a r y ammonium
h y d ro x id e w ith th e
w a te r.
f o r m a tio n o f a t e r t i a r y
a m in e , a n o l e f i n ,
an d
T h e q u a t e r n a r y ' ammonium h y d r o x i d e w as e a s i l y p r e p a r e d b y
-
29-
r e a c t i o n o f t h e q u a t e r n a r y ammonium i o d i d e w i t h s i l v e r o x i d e .
In
m o s t c a s e s t h e m e c h a n is m o f t h e H ofm ann r e a c t i o n h a s i n v o l v e d a n
E -2 tr a n s e lim in a tio n .
t h i s w as n o t t h e c a s e .
H o w e v e rj, t h e r e w e re som e e x a m p le s w h e re
^ ^
C om pound 2 0 .w o u ld b e e x p e c t e d t o u n ­
d e rg o a n o rm a l E -2 t r a n s e l i m i n a t i o n .
I n 1 9 7 1 A r c h e r h a s show n t h a t t h e r e w as a n im p ro v e m e n t i n t h e
y i e l d d u r i n g H ofm ann e l i m i n a t i o n i f r e d u c e d p r e s s u r e w e r e u s e d .
^ ^
By u s i n g r e d u c e d p r e s s u r e t h e H ofm ann e l i m i n a t i o n c o u l d b e c a r r i e d
o u t a t a lo w e r te m p e r a tu r e t h a n n o r m a lly r e q u i r e d .
A rc h er h as s ta te d
t h a t c y c l o p r o p a n e c o u l d b e r e a d i l y p r e p a r e d b y t h i s m e th o d i n 30 -
$Ofo y i e l d s .
P y r o l y s i s o f t h e q u a t e r n a r y ammonium h y d r o x i d e ( 2 0 ) w as accom ­
p l i s h e d b y tw o m e t h o d s „
B o t h . o f t h e s e m e th o d s i n v o l v e d a n a p p a r -
( 33)
a t u s v e r y s i m i l a r t o t h a t u s e d b y W a itk u s a n d c o w o rk e rs ,,
T h e f i r s t m e th o d u s e d f o l l o w e d W a itk u s a n d c o w o r k e r s 1 p r o c e d u r e
i n t h e i r p r e p a r a tio n o f trim e th y le n e c y c lo p ro p a n e .
in v o lv e d i n j e c t i n g
d ro x id e i n t o
T h i s m e th o d
a 10% s o l u t i o n o f t h e q u a t e r n a r y ammonium h y ­
a f l a s k p re h e a te d to
I4..3 mm Hg ( n i t r o g e n
a c e to n e b a th .
(3 3 )
),
210°C a t a re d u c e d p r e s s u r e o f
T h e p r o d u c t s w e re c o l l e c t e d i n
a d ry i c e /
T h e s e c o n d m e th o d u s e d w as t h a t o f A r c h e r .
H is m e th o d i n v o l v e d t h e r e m o v a l ■o f w a t e r a t w a t e r pump p r e s s u r e
a n d U o 'C j l o w e r i n g t h e p r e s s u r e t o
a s lo w a s p o s s i b l e
( . I ^ mm H g ) ;
and t h e n s lo w ly r a i s i n g t h e te m p e r a tu r e u n t i l th e p y r o l y s i s to o k
-3 0 -
p la c e .
U s in g t h i s m e th o d t h e p y r o l y s i s a p p e a r e d t o t a k e p l a c e a t
a b o u t 15)0 C .
200°C .
H o w ev er t h e t e m p e r a t u r e w as r a i s e d t o
A g a in t h e p r o d u c t s w e re c o l l e c t e d i n
a m aximum o f
a d r y i c e / a c e to n e
b a th .
T he r e a c t i o n t h a t to o k p la c e d u rin g th e p y r o ly s is o f th e q u a­
t e r n a r y ammonium h y d r o x i d e ( 2 0 ) i s
show n b e l o w .
B e fo re th e d i f ­
f e r e n t s p e c t r a w e re t a k e n t h e s a m p le w a s w a sh e d w i t h d i l u t e h y d r o ­
c h lo ric
a c i d a t O'C t o re m o v e t h e t r i m e t h y l a m i n e .
s p e c t r a l d a t a a r e s u m m a riz e d i n t h e t a b l e s b e lo w .
The d if f e r e n t
The u l t r a -
_31—
TABLE I I
UY SPECTRUM OF ] ,l-DIMETHYL-2,3-DIMETHYLENECYCLOPROPANE AND RELATED
COMPOUNDS
C om pound
UV S p e c tr u m (nm )
XMAX
SHOULDER
SHOULDER
x MAX
SHOULDER
SHOULDER
x MAX
[ 2
—
2 :
ZZ
—
—
R e fe re n c e
227
236
220
232
225
240
27
250
67
x MAX =
248
x MAX =
x MAX -
249
240
7 0
-3 2 TABLE I I I
NMR SPECTRUM OF I , I-D IM ETH Y L-2,3-D IM ETHYLENECYCLOPROPANE AND RELATED
COMPOUNDS
Com pound
D e l t a V a lu e s
Ha
Ha
Hb
He
Ha
Hb
He
Ha
R efe re n c e
—
5 . 2 8 (S)
(4H)
5.1 7 (S)
=
I . I S ( S ) (6H)
—
5 .5 0 (M )
(2H)
—
5.27(M)
(2H)
1.5 6 (M)
(2H)
=
5 . 0 8 (S)
(2H)
—
4 . 6 0 (S)
(2H)
—
2 .5 5 (M )
(4H)
—
4.55(M )
(2H)
—
4.83(M )
(2H)
=
4 . 9 7 ( D ) (4H)
(J= 13 CYCLES)
—
2 7
72
72
Hb
Ha
73
-3 3 TABLE IV
MASS SPECTRUM OF 3., I-P IM E T HYL-2, 3-DIMETHYLENECYCLOPROPANE AND RELATED
C OMPOIINDSf-
X 27)
X]
C
m/e
Il
■A.
<
re la tiv e
in te n s ity
m/e
(3 0 )
re la tiv e
in te n s ity
m/e
re la tiv e
in te n s ity
9h
13
66
87
79
18
93
18
65
92
78
100
79
100
39
100
77
78
13
63
U5
12
77
73
52
82
65
IU
51
72
53
30
5o
50
52
21
39
U2
51
36
38
IU
5o
20
37
11
Ul
(b )
28
Uo
(b)
27
23
18
39
53
26
lU
36
(b )
32
(b)
28
(b)
27
(b )
(a )
i n c l u d i n g o n l y r e l a t i v e i n t e n s i t i e s above 10%
(b )
h ig h b a c k g ro u n d c o u n t
-3 b '”
v i o l e t s p e c tr u m i s
l i s t e d i n T a b le I I ,
n a n c e s p e c tr u m i n T a b le I I I ,
t h e n u c l e a r m a g n e tic r e s o ­
a n d t h e m a ss s p e c t r u m i n T a b l e IV .
The u l t r a v i o l e t s p e c tr u m o f t h i s p y r o l y s i s p r o d u c t l e f t l i t t l e
d o u b t t h a t i t in v o lv e d a c o n ju g a te d s y s te m .
The n u c l e a r m a g n e tic
r e s o n a n c e s p e c t r u m g a v e s i g n a l s a t 5 . 1 7 a n d 5 .2 8
in d ic a tin g ,
a le n t.
(d e lta u n its )
a s e x p e c t e d , t h a t t h e m e t h y l e n e p r o t o n s w e re n o t e q u i v ­
A ls o a s i n g l e t a t 1 .1 8 t h a t i n t e g r a t e d f o r 6 p r o t o n s i n ­
d i c a t e d t h e 'e q u i v a l e n t gem d i m e t h y l p r o t o n s .
T h e m a ss s p e c tr u m
o f t h e p y r o l y s i s p r o d u c t h a d a p a r e n t p e a k a t m /e Pb (18% ) a n d a
b a s e p e a k a t m /e 79 (100% ) w h ic h i n d i c a t e d ,
a m e th y l g ro u p t o
g iv e tw ic e an a l l y l i c
as e x p e c te d , lo s s o f
io n o r r a d ic a l.
A ll o f th e
above s p e c t r a l d a t a c o r r e l a t e d e x tr e m e ly w i l l w ith t h e p ro p o s e d
s tru c tu re
( 7) f o r th e p y r o ly s is p ro d u c t.
D e s p ite th e
a c c u m u la tio n o f c o n v in c in g s p e c t r a l e v id e n c e t h a t
I , l- d im e th y l- 2 ,3 - d im e th y le n e c y c lo p r o p a n e h a d b e e n s y n th e s iz e d , i t
w as f e l t t h a t a d e r i v a t i v e
s h o u ld b e a tte m p te d .
A lth o u g h t h e d ie n e
d e c o l o r i z e d b r o m in e i n c a r b o n t e t r a c h l o r i d e , t h e r e w as n o t e n o u g h
o f t h e b ro m in a tio n p ro d u c t t o b e c h a r a c te r i z e d .
p r o d u c t w as c o m b in e d w i t h m a l e i c a n h y d r i d e
A ls o t h e p y r o l y s i s
a s show n b e l o w .
The
r e a c t i o n w as r u n i n e t h e r a n d a f t e r a n h o u r a s o l i d h a d p r e c i p i t a t e d
o ut o f s o lu tio n .
ta tiv e
I n t h e e t h e r s o l u t i o n t h e r e re m a in e d a q u a n t i ­
am o u n t o f m a l e i c a n h y d r i d e .
T h at t h i s P ie ls -A ld e r r e a c tio n
w o u ld n o t go w as i n d i c a t e d b y t h e f a c t t h a t d i m e t h y l e n e c y c lo p r o p a n e
—3 5 ~
»
POLYMER
d id n o t g iv e an a d d u c t w ith te t r a c y a n o e th y l e n e .
+
( 27)
As a D i e l s - A l d e r a d d u c t c o u l d n o t b e p r e p a r e d , i t w as n e x t
d e c id e d t o
a tte m p t a c a t a l y t i c h y d ro g e n a tio n .
A r e c e n t book by
R y la n d e r h a s p r e s e n te d a d is c u s s io n o f th e d i f f e r e n t a s p e c ts o f
c a t a l y t i c h y d ro g e n a tio n o v e r p la tin u m m e ta ls and s h o u ld b e re a d
b e f o r e a tte m p tin g a h y d ro g e n a tio n .
5 $ P a l l a d i u m on c a r b o n a s i t
(6 5 0
T h e c a t I y s t c h o s e n w as
c a t a l y t i c a l l y r e d u c e d 3* 3 - d i m e t h y l -
c y c l o p r o p e n e t o I , 1 - d i m e t h y l c y c l o p r o p a n e i n 95$ y i e l d .
s in c e
a n a m in e w as p r o d u c e d b y t h e p y r o l y s i s r e a c t i o n ,
h a v e b e e n know n t o p o i s o n h y d r o g e n a t i o n s
a c e tic
a c i d w e re a d d e d t o t h e r e a c t i o n m i x t u r e .
( 66 )
A ls o
a n d a m in e s
tw o e q u i v a l e n t s o f
The h y d ro g e n a tio n ,
a s show n b e lo w , w as c a r r i e d o u t a t 0°C a n d w as b e l i e v e d t o
g iv e
-
a c is
s tru c tu re
36-
a s trim e th y le n e c y c lo p ro p a n e gave c i s - 1 , 2 ,3 - tr im e th y l-
(33)
c y c lo p r o p a n e u p o n c a t a l y t i c h y d r o g e n a t i o n . v
'
T he m a jo r p ro d u c t
o f th e h y d n o g e n o ly s is r e a c t i o n i n d i c a t e d t h a t th e d ie n e h a d a b s o rb ­
e d tw o m o le s o f h y d r o g e n b y i t s
m ass s p e c tr u m .
p a r e n t p e a k a t m /e 98 (19%) i n t h e
T h e o n l y s a t u r a t e d co m pound t h a t t h i s
a l l o w e d w as
1 , 1 , 2 , 3 - t e t r a m e t h y l c y c l o p r o p a n e ; . h o w e v e r t h e a b s o r p t i o n o f tw o
m o le s o f h y d r o g e n c o u l d a l s o b e e x p l a i n e d b y t h e p r o d u c t i o n o f a n
a lk e n e v i a a r i n g
ghow n b e l o w .
d e lta .
The p o s s ib le p ro d u c ts a re
T he n u c l e a r m a g n e tic r e s o n a n c e s p e c tr u m ' o f t h e h y d ro -
g e n o ly s is p ro d u c t,
o f th e r in g
o p e n in g r e a c t i o n .
a lth o u g h v e r y h a r d t o i n t e r p r e t ,
opened p o s s i b i l i t i e s
e lim in a te d a l l
a s t h e s i g n a l s w e re a b o v e 1 . 0
C l o s e r i n s p e c t i o n o f t h e nm r s p e c t r u m r e v e a l e d a s i n g l e t a t
1 . 0 d e l t a t h a t i n t e g r a t e d f o r 3' p r o t o n s a n d c o u l d b e d u e t o
t h e gem d i m e t h y l g r o u p s „
p ro to n s .
one o f
The r e s t o f th e p e a k s i n t e g r a t e d f o r 11
A q u a r t e t c o u l d b e p i c k e d - o u t t h a t w as c e n t e r e d a t 0.85
-3 7 -
cTh
S
CH^CHgrC-CH-CH2
CH3
^ 2
CH^- CH- C^C HgCH^
CH3
CH3
+
C Hg-C H-CH-C H -C Hg
CH 3
d e l t a a n d h a d J-=U c y c l e s .
T h is q u a r t e t c o u ld b e due t o th e r i n g
p r o to n s b e in g s p l i t b y t h e a d ja c e n t m e th y l g ro u p s .
a d o u b l e t c e n t e r e d a t 0 . 8 3 d e l t a a n d h a d J=U c y c l e s .
A l s o t h e r e w as
T h is d o u b le t ■
c o u ld b e due t o t h e m e th y l g ro u p s n e x t t o t h e r i n g p r o t o n s .
a ls o
It
a p p e a r e d t h a t t h e o t h e r gem d i m e t h y l g ro u p w as u n d e r t h e
d o u b le t.
T h e nm r s p e c tr u m a l s o w as c o n s i s t e n t w i t h t h e p r o d u c t
h a v i n g a c i s s t r u c t u r e 5 a s i f t h e p r o d u c t w e re t r a n s t h e gem d i m e t h y l
g r o u p s w o u ld b e e q u i v a l e n t ,
T he m ass s p e c tru m
o f th e h y d ro g e n a te d p ro d u c t a ls o
c o rre la te d
. -
38-
v e r y w e ll, w i t h t h e m ass s p e c t r a o f I , I 52 , 2 - te tr a m e th y lc y c lo p r o p a n e
a n d I 5I 5 2 - t r i m e t h y l c y c l o p r o p a n e 5 a s c a n b e s e e n i n T a b l e V .
T he i n f r a r e d s p e c tru m o f t h e h y d ro g e n a te d p r o d u c t h a d a b s o r p ­
t i o n s b e t w e e n 9 „ 6 - 9 „ 8 5 m i c r o n s a n d b e t w e e n 3 - 2 - 3 .- 3 m i c r o n s w h ic h
i n d i c a t e d , b u t w as n o t c o n c l u s i v e f o r ,
a c y c lo p r o p a n e r i n g .
T h e a b o v e c o m b in e d e v i d e n c e i n d i c a t e d v e r y s t r o n g l y t h a t t h e
s a t u r a t e d c y c lo p r o p a n e h a d b e e n m ade,
and t h a t in d e e d i t s
p re c u rso r,
I , l- d im e th y l- 2 ,3 - d im e th y le n e c y c lo p r o p a n e h a d b e e n s y n th e s iz e d b y
th e p y ro ly s is re a c tio n .
I n c o n c lu s io n , t h e r e f o r e ,
a l l o f t h e c o m b in e d e v i d e n c e i n d i ­
c a te d s tr o n g ly t h a t in d e e d th e s t r a i n e d h y d ro c a rb o n I , l-d d m e th y l2 , 3 -d im e th y le n e c y c lo p ro p a n e h a d b e e n s y n th e s iz e d , how ever i n v e r y
poor o v e ra ll y ie ld
( l e s s t h a n 1% ).
U pon l o o k i n g b a c k ,
a n o t h e r m e th o d
o f s y n t h e s i z i n g t h e d im e th y le n e com pound, p e rh a p s i n h i g h e r o v e r a l l
y i e l d , b e c a m e a p p a r e n t a s show n b e l o w .
J a r r e t t h a s show n t h a t
CH0OH
“39"
c is
in
a n d t r a n s c a n o n i c a c i d s c a n b e p r o d u c e d fr o m d e l t a - 3 - c a r e n e
7% y i e l d
and th e r e s t o f th e r e a c tio n s f a l l in to p la c e „
TABLE V
MASS SPECTRUM OF I 5I jl 2 , 3-TEIRAMETHTLCTCLOPROPANE AND RELATED
(a )
COMPOUNDS ^ '
re la tiv e '
in te n s ity
m/e
m/e
re la tiv e
in te n s ity
m/e
re la tiv e
in te n s ity
98
19
98
23
Qh
29
83
52
83
98
69
61
15
56
IU
10
12
55
100
55
U2
10
100
h3
23 .
ia
100
53
12
la
75
39
25
hh
26^
39
hh
27
18
29
IU
28
70
96-
#
k3
hi
■
' 90
ho
65
3 0 Cb )
39
U2
27
'
32
29
35(1)
28
65 (1)
27
5U(a)(b)
lgCb)
26
(a )
in c lu d in g o n ly r e l a t i v e i n t e n s i t i e s above 10%
(b)
h ig h background count
CONCLUSION
T h e - u l t r a v i o l e t s p e c t r u m , n u c l e a r m a g n e t i c r e s o n a n c e s p e c tr u m
a n d t h e m a ss s p e c t r u m i n d i c a t e t h a t I , l - d i m e t h y l - 2 , 3 - d i m e t h y l e n e c y c l o p r o p a n e w as s y n t h e s i z e d s t a r t i n g
ly tic
fro m d e l t a - 3 - c a r e n e .
C a ta ­
h y d r o g e n a tio n o f t h e d im e th y le n e c y c lo p ro p a n e o f f e r e d f u r t h e r
p ro o f.
The s p e c t r a l d a t a on t h e h y d ro g e n a te d p r o d u c t i n d i c a t e d
t h a t i t w as 1 , 1 , 2 , 3 - t e t r a m e t h y l c y c l o p r o p a n e .
In
a d d i t i o n t h e d i a c i d , com pound 1 7 i n
u se fu l i f i t s
y i e l d s c o u l d b e im p r o v e d .
sh o w n m uch u s e i n t h e f i e l d
o f a d ip ic
m ig h t be
D ic a rb o x y lic a c id s have
o f s y n t h e t i c p o ly m e r s s u c h a s t h e u s e
a c id i n p o ly a m id e s ( e . g , ,
p h t h a l a t e fro m t e r e p h t h a l i c
sch em e I ,
n y lo n ) ,
a c id i n p o ly e s te r s
and d im e th y l- te r e ( e.g.,
d a c ro n ) .
^
EXPERIMENTAL
M e l t i n g p o i n t s w e re d e t e r m i n e d o n a F i s h e r J o h n s m e l t i n g p o i n t
a p p a r a tu s b e tw e e n g l a s s d i s c s o r i n u n s e a le d c a p i l l a r y tu b e s i n a
T h i e l e t u b e f i l l e d w i t h Dow C o r n in g £$0 s i l i c o n e f l u i d
and a l l a re
u n c o rre c te d .
G as l i q u i d c h r o m a t o g r a p h i c ( g l c
) a n a l y s e s w e re c a r r i e d o u t
e i t h e r o n a n F&M M o d e l UOO o r A u t o p r e p A -7 0 0 g a s c h r o m a t o g r a p h «
T h e n u c l e a r m a g n e t i c r e s o n a n c e s p e c t r a w e re o b t a i n e d o n a
V a r i a n A s s o c i a t e s , I n c . , M o d e l A- 6 0 s p e c t r o m e t e r o p e r a t e d a t ro o m
te m p e ra tu re .
T h e com p o u n d s w e re r u n . i n c a r b o n t e t r a c h l o r i d e w i t h
TMB a s a n i n t e r n a l ' s t a n d a r d ,
o t i n S ila n o r-C
( C D C l^ w ith 1% TMS),
o r i n d e u te r iu m o x id e w ith no s t a n d a r d .
T h e u l t r a v i o l e t a b s o r p t i o n s p e c t r a w e re t a k e n i n h e x a n e on a
G a r y M o d e l II 4. s p e c t r o p h o t o m e t e r .
I n f r a r e d s p e c t r a w e re o b t a i n e d o n e i t h e r a B eckm an IR -^ A o r
a B eck m an I R - 2 0 s p e c t r o p h o t o m e t e r u s i n g p o l y s t y r e n e
as a s ta n d a rd .
M ass s p e c t r a w e re o b t a i n e d o n a V a r i a n M at CH $ s p e c t r o m e t e r .
T h e s a m p le s w e re i n t r o d u c e d q n t o t h e m a ss s p e c t r o m e t e r b y w ay o f a
V a r ia n A e ro g ra p h s e r i e s 1 7 0 0 g a s c h ro m a to g ra p h .
T h e o z o n o l y s i s r e a c t i o n w as c a r r i e d o u t u s i n g a W e ls b a c h
M odel T -2 3 l a b o r a t o r y o z o n a to r .
re p o r te d e ls e w h e re „
T he s o l v e n t s and c o n d itio n s
a re -
~k3~
T h e d e l t a - 3 " C a r e n e w as o b t a i n e d f r o m t h e D e p a r tm e n t o f C h e m ic a l
E n g i n e e r i n g , M o n ta n a S t a t e U n i v e r s i t y . i n g w i t h w a t e r (10% m e t h a n o l )
I t w as p u r i f i e d b y e x t r a c t ­
and th e n d i s t i l l a t i o n u n d e r n itr o g e n
u s i n g a T o d d c o lu m n ( g l a s s b e a d c o lu m n ) w i t h a 3 0 ‘1 r a t i o t i m e r .
The f r a c t i o n b o i l i n g
a t 166 - 167 ° C (6i|.2 mm Hg) w as c o l l e c t e d a n d
u s e d i n th e fo llo w in g e x p e rim e n ts .
A fte r d i s t i l l a t i o n th e d e lta -
3 - c a r e n e w as s t o r e d u n d e r n i t r o g e n a t 5 ° C .
(3 ? )
P r e p a r a t i o n o f R -3 iU -e p o x y c a ra n e , 1 1 : v '
D ry p o w d e re d c a l c i u m c a r b o n a t e ( 1 0 . 0 g ra m s ,
(5 9 m l) , p u r i f i e d d io x a n e
„1 m o l e ) , w a t e r
(1 0 0 m l) a n d N - b r o m o s u c c in im id e ( 3 5 . 0
g ra m s,
.2 m o le s ) w e re a d d e d i n t h a t o r d e r t o d e l t a - 3 - c a r e n e
g ra m s,
. 07 I4 m o l e s ) .
T h e m i x t u r e . w as s t i r r e d
( t e m p e r a t u r e r o s e t o lj.2° C ) .
(2 0 0 m l ) , f i l t e r e d ,
and th e f i l t r a t e
(1 0 .0
f o r a b o u t 2 .5 h o u rs
T h e m i x t u r e w as p o u r e d i n t o w a t e r
a n d t h e s o l i d r e s i d u e w as w a s h e d w i t h e t h e r ,
w as e x t r a c t e d w i t h e t h e r ( 3 X 1 5 0 m l ) .
The
c o m b in e d e x t r a c t w as f i r s t w a sh e d w i t h w a t e r ( 3 % 1 0 0 m l ) , t h e n
w a s h e d w i t h s o d iu m t h i o s u l p h a t e
(N a^S gO ^) (
100 m l ) .
T h e w a sh ­
e d e x t r a c t w a s s t r i p p e d o f s o l v e n t a n d 1 0 0 m l o f t - b u t y l a l c o h o l w as
added.
T o t h i s w as a d d e d f r e s h l y p r e p a r e d p o t a s s i u m t - b u t o x i d e
(6 g ra m s p o t a s s i u m p l u s 1 5 0 m l t - b u t y l a l c o h o l )
w as a l l o w e d t o
s ta n d f o r 3 h o u rs , p o u re d i n to
an d t h e m ix tu r e
200 m l o f w a te r and
"Ijil.e x tr a c te d w ith e th e r ( 3 X 100 m l ) .
s e v e r a l tim e s w ith w a te r .
T h e e t h e r l a y e r w as w a sh e d
U pon v ac u u m d i s t i l l a t i o n t h e r e r e m a in e d
3 .8 8 g ra m s (35% ) o f a . c o l o r l e s s l i q u i d .
P r e p a r a t i o n o f o c-3 , L - e p o x y c a r a n e , 1 0 :
bp
7U C ( l l mm Hg)
( 18)
A s o l u t i o n c o n t a i n i n g ' a p p r o x i m a t e l y 2k g ra m s (
.1 8 m o le s )
o f p e r b e n z o i c a c i d , p r e p a r e d b y t h e m e th o d o f G ilm a n a n d B l a t t
( 7 l)
,
i n 300 m l o f c h l o r o f o r m w as p u t i n a 5>00 m l 3 - n e c k f l a s k e q u i p p e d
w ith a th e rm o m e te r,
a c o n d e n se r,
and c o o le d b y an i c e b a th .
a d ro p p in g f u n n e l, m a g n e tic s t i r r e r
1 3 . 8 g ra m s (
. 1 m o le ) o f d e l t a - 3 - c a r e n e
w as a d d e d v i a t h e d r o p p i n g f u n n e l o v e r a p e r i o d o f 0 . 5 h o u r s d u r i n g
w h ic h t i m e t h e t e m p e r a t u r e w as m a i n t a i n e d b e tw e e n 1 5 -2 0 ° C .
s o l u t i o n w as t h e n a l l o w e d t o
p e ra tu re .
tio n
s tir
o v e r n ig h t ( l8 h o u rs )
T h is
a t ro o m te m ­
T i|e e x c e s s p e r b e n z o i c a c i d w a s d e s t r o y e d b y s l o w a d d i ­
o f 1 5 0 m l o f 10% s o d iu m t h i o s u l f a t e
w as p o u r e d i n t o
(NagSgO ) .
a s e p a ra to ry fu n n e l and th e
T h is s o lu tio n
a q u e o u s l a y e r re m o v e d .
T h e c h l o r o f o r m l a y e r w as w a s h e d w i t h 10% s o d iu m b i c a r b o n a t e
( 2 X
150 m l ) , th e n w ith a s a t u r a te d s a l t s o l u t i o n ( 3 X 100 m l ) and
t h e n d r i e d o v e r a n h y d r o u s s o d iu m s u l f a t e .
U pon e v a p o r a t i o n a n d
v a c u u m d i s t i l l a t i o n t h e r e w as o b t a i n e d 6 . 7 g ra m s (UU%) o f a c o l o r le s s liq u id .
bp
6 6 ° C ( . 8 mm Hg)
P re p a ra tio n o f 3 ^
5 . 0 g ra m s (
30 m l o f a , I M
l i C - c a r a n e d i o l , l l |. :
„033 m o le s ) o f cc -3 5li - e p o x y c a r a n e w as a d d e d t o
s u lfu ric
n e t i c a l l y f o r 2k h o u r s „
a c id s o lu tio n i n
a fla s k
a n d s t i r r e d m ag­
T h e a q u e o u s m i x t u r e w as e x t r a c t e d w i t h
c h l o r o f o r m '( 3 X 5>0 m l ) a n d w a s h e d w i t h 10% s o d iu m b i c a r b o n a t e a n d
th e n w ith a s a tu r a te d s a l t s o lu tio n .
d r i e d o v e r a n h y d r o u s s o d iu m s u l f a t e
T h e c h l o r o f o r m s o l u t i o n w as
and upon e v a p o ra tio n o f th e
s o l v e n t t h e r e r e m a i n e d 3 . 6 g ra m s (83% ) o f a c o l o r l e s s
mp
s o lid .
( p u r i f i e d b y s u b l i m a t i o n - 68 C - I . 3 mm H g)
8 8 °C
A c id c l e a v a g e o f g - 3 , U - e p o x y c a r a n e :
3 . 0 g ra m s (
o f a .IM
.0 2 m o le s ) o f p ~ 3 , l|.~ e p o x y c a ra n e w as a d d e d t o 30 m l
s u lfu ric
a c i d s o l u t i o n a n d w as s t i r r e d m a g n e t i c a l l y f o r
2k h o u r s 0 T h i s s o l u t i o n w as e x t r a c t e d w i t h c h l o r o f o r m ( 3 % 3 0 m l )
and th e
o r g a n i c l a y e r w as w a s h e d w i t h 10% s o d iu m b i c a r b o n a t e a n d t h e n
w ith a s a tu r a te d s a l t s o lu tio n .
o v e r a n h y d r o u s s o d iu m s u l f a t e
T h e c h l o r o f o r m l a y e r w as t h e n d r i e d
and upon e v a p o ra tio n o f s o lv e n t th e r e
r e m a i n e d ,83 g ra m s (23% ) o f a n o i l y s o l i d . T h e p r o d u c t s w e re n o t
f u r t h e r c h a r a c t e r i z e d i n t h i s l a b o r a t o r y , b u t h a v e b e e n b y K ro p p
P r e p a r a tio n o f th e k e to -a ld e h y d e , 1 3 =
2 . 0 g ra m s ( .0 1 2 m o le s ) o f t h e t r a n s d i o l ,
3 p , U c C - c a r a n e d io l,llj.,
w as m ix e d w i t h I).. 33 g ra m s (.0 1 3 3 m o le s ) o f s o d iu m b i s m u t h a t e (N aB iO ^)
8 m l w a te r,
m l o f 33% p h o s p h o r i c a c i d a n d 30 m l o f e t h e r i n a
ro u n d b o tto m e d f l a s k e q u ip p e d w ith a c o n d e n s e r .
T h e r e a c t i o n m ix ­
t u r e w as s t i r r e d m a g n e t i c a l l y u n t i l t h e c o l o r o f t h e s o d iu m b i s ­
m u th a t e h a d d i s a p p e a r e d ( a p p r o x . 18 h o u r s )
.
t h a t r e m a i n e d w as re m o v e d b y v ac u u m f i l t r a t i o n .
s y s t e m w as s e p a r a t e d a n d t h e
( 2 X '^O m l ) .
The w h ite s o l i d
T h e tw o p h a s e
a q u e o u s l a y e r w as e x t r a c t e d w i t h e t h e r
T h e c o m b in e d e t h e r f r a c t i o n s w e re d r i e d o v e r a n h y ­
d r o u s s o d iu m s u l f a t e .
V acuum d i s t i l l a t i o n
( 86 %) o f a p a l e y e l l o w l i q u i d .
bp
g a v e a y i e l d o f 1 .7 g ra m s
8 7 -8 8 ° C ( 1 .3 mm Hg)
CLEAVAGE OF DELTA-3-CIRENE
I.
S o d iu m p e r i o d a t e - p o t a s s i u m p e r m a n g a n a te o x i d a t i o n :
1 .0
g ra m s (
g ra m (
. OO7 I4 m o le s ) o f d e l t a - 3 - c a r e n e w as a d d e d t o
.0 2 2 m o le s ) o f p o t a s s i u m c a r b o n a t e i n 300 m l o f w a t e r .
T h e r e a c t i o n m i x t u r e w as s t i r r e d m a g n e t i c a l l y f o r 18 h o u r s d u r i n g
w h ic h t i m e t h e t e m p e r a t u r e r e m a i n e d b e t w e e n 1 3 - 2 0 ° G ,
m i x t u r e w as f i l t e r e d
The r e a c t i o n
and e x t r a c t e d w ith e t h e r ( 3 % 30 m l ) .
T he
c o m b in e d e t h e r f r a c t i o n s w e re d r i e d o v e r a n h y d r o u s s o d iu m s u l f a t e ,
s t r i p p e d o f s o l v e n t and vacuum d i s t i l l e d .
T h e r e w as r e c o v e r e d .3
g ra m s o f s t a r t i n g m a t e r i a l a n d ..1 3 g ra m s o f a f r a c t i o n t h a t b o i l e d
b e t w e e n 7 0 - 1 3 0 ° C (I+ .8 mm H g ) .
o f th e fla s k .
T h e r e m a i n d e r w as t a r i n t h e b o t t o m
3 -Oi+
~k7~
( *~>9)
2 . B i s - t r i p h e n y l s i l y l c h r o m a te o x i d a t i o n ;. K y
B i s - t r i p h e n y l s i l y l c h r o m a te w as p r e p a r e d b y t h e m e th o d o f B a k e r
and G a rric k .
1 5 .0
1 5 . 0 g ra m s ( .051+ m o le s ) o f t r i p h e n y l s i l a n o l ,
g ra m s ( .1 5 m o le s ) o f c h ro m iu m t r i o x i d e
a n d 5 . 0 g ra m s o f
a n h y d r o u s m a g n e siu m s u l f a t e w e re m ix e d i n 1+50 m l o f c a r b o n t e t r a ­
c h lo rid e .
T h e m i x t u r e w as p u t i n
a 500 m l l i g h t - t i g h t f la s k
w as s h a k e n i n a w r i s t - a c t i o n s h a k e r f o r 2 3 h o u r s .
m i x t u r e w as f i l t e r e d
and th e f i l t r a t e
and
The re d -o ra n g e
w as s t r i p p e d o f s o l v e n t .
R e c r y s t a l i i z a t i on o f t h e d a r k r e s i d u e fro m h o t h e p ta n e r e s u l t e d
i n 1 0 . 3 5 g ra m s ( 6 0 . 5 # ) o f a n o r a n g e s o l i d .
mp
l5 3 -l5 5 ° c
9 . 1 5 g ra m s ( .011+ m o le s ) o f b i s - t r i p h e n y l s i l y l c h r o m a te i n 75
m l o f c a r b o n t e t r a c h l o r i d e w as a d d e d t o
o f d e lta -3 -c a re n e .
2 . 0 g ra m s ( . Oil+ m o le s )
T h e m i x t u r e w as h e a t e d m i l d l y (1+ 0-50°C ) i n a
w a te r b a th f o r 15 h o u r s .
a n d w a t e r w e re a d d e d .
T h e s o l v e n t w as s t r i p p e d o f f a n d e t h e r
T h e r e a c t i o n m i x t u r e w as e x t r a c t e d 2 m ore
tim e s w ith 50 m l o f e t h e r .
a n h y d r o u s s o d iu m s u l f a t e
T h e c o m b in e d f r a c t i o n s w e re d r i e d o v e r
a n d v ac u u m d i s t i l l e d t o y i e l d 1 . 5 gram s
o f d e lta -3 -c a re n e .
T h i s m e th o d w as j u d g e d n o t t o b e f e a s i b l e b e c a u s e o f t h e am o u n t
o f s t a r t i n g m a t e r ia l re c o v e r e d and th e
am o u n t o f b i s - t r i p h e n y l s i l y l
c h r o m a te n e e d e d t o p e r f o r m t h e - o x i d a t i o n .
3 . O z o n o ly s is
A. P r e p a r a t i o n o f t h e k e t o - a c i d , 1 6 :
l)
"w ith h y d r o g e n p e r o x i d e w o rk u p o f t h e o z o n id e
5 1 .0
a c e tic
to
g ra m s (
.3 7 5 m o le s ) o f d e l t a - 3 - c a r e n e
a c i d w e re a d d e d t o t h e r e a c t i o n v e s s e l .
a W e ls b a c h o z o n a t o r f o r 7 . 5 h o u r s
th e o re tic a lly
in to
a fla s k
.91 m o le s o z o n e ) „
a n d 3 5 0 m l o f 5%
T h i s w as c o n n e c t e d
( 6 . 2 2 g ra m s o f o z o n e p e r h o u r ,
T h e r e a c t i o n m i x t u r e w as p o u r e d
a n d 1 0 m l o f 30% h y d r o g e n p e r o x i d e a n d 300 m l o f w a t e r
w e re a d d e d , a n d t h e m i x t u r e w as r e f l u x e d f o r 2 h o u r s .
The e x c e ss
h y d r o g e n p e r o x i d e w as d e s t r o y e d b y a d d i t i o n o f s o d iu m i o d i d e a n d
t h e l i b e r a t e d i o d i d e w as d e s t r o y e d w i t h s o d iu m t h i o s u l f a t e .
t h e r e a c t i o n m i x t u r e w as e x t r a c t e d w i t h e t h e r ( 3 I
T hen
10 0 m l ) and t h e
c o m b in e d e t h e r f r a c t i o n s w e re d r i e d o v e r a n h y d r o u s s o d iu m s u l f a t e .
V acuum d i s t i l l a t i o n y i e l d e d 7 . 0 g ra m s (10% ) o f a b ro w n l i q u i d ,
bp
1 3 0 -1 6 0 °C
2)
1 0 .0
( 1 . 3 mm Hg)
w ith J o n e s o x id a tio n o f th e
g ra m s (
o z o n id e
.0 7 5 m o le s ) o f d e l t a - 3 - c a r e n e i n 300 m l o f e t h y l
a c e t a t e w as o z o n i z e d i n a n i c e - s a l t b a t h .
g ra m s o f o z o n e p e r h o u r , t h e o r e t i c a l l y
s tr ip p e d o ff th e
A f t e r 2 . 5 h o u r s (lj..9
.2 6 m o le s ) t h e
o z o n i d e a n d 1 5 0 m l o f a c e t o n e w as a d d e d .
a c e t o n e s o l u t i o n o f t h e o z o n i d e w as t h e n t i t r a t e d
r e a g e n t u n t i l a b ro w n c o l o r p e r s i s t e d
re a g e n t).
s o l v e n t w as
T h e s o l u t i o n w as a l l o w e d t o
The
a t 0° C w i t h J o n e s
( r e q u i r e d 1 ^ .2 m l o f J o n e s
s ta n d f o r
.5 h o u rs and th e n
-b 9 ~
300 m l o f w a t e r w as a d d e d .
and th e
M o st o f t h e
- .
a c e t o n e w as s t r i p p e d o f f
a q u e o u s p o r t i o n w as e x t r a c t e d w i t h e t h e r ( 3 X 73 m l ) .
T h e e t h e r f r a c t i o n s w e re c o m b in e d a n d d r i e d o v e r a n h y d r o u s so d iu m
s u lfa te „
liq u id .
3)
V acuum d i s t i l l a t i o n y i e l d e d 3 . 0 g ra m s (22% ) o f a b ro w n
bp
1 3 0 -1 3 0 °C
( 0 . 3 mm H g)
w ith fo r m ic a c id and h y d ro g e n p e r o x id e o x id a tio n
1 0 . 0 g ra m s o f m a t e r i a l t h a t r e m a i n e d a f t e r o z o n o l y s i s o f d e l t a 3 - c a r e n e i n m e t h a n o l w as r e a c t e d w i t h f o r m i c a c i d a n d h y d r o g e n
p e r o x id e
a c c o rd in g t o th e p ro c e d u re o f B a ile y .
T he 1 0 .0
g ra m s o f p e r o x i d i c r e s i d u e w as d i s s o l v e d i n 33 m l o f 90 % f o r m i c
a c i d a n d 17 m l o f 30% h y d r o g e n p e r o x i d e w as a d d e d .
The s o lu tio n
w as h e a t e d g e n t l y a n d a s p o n t a n e o u s , r e a c t i o n t o o k p l a c e .
W hen t h e
r e a c t i o n h a d c e a s e d t h e r e a c t i o n m i x t u r e w as d i s s o l v e d i n e t h e r
a n d e x t r a c t e d s e v e r a l t i m e s w i t h w a t e r t o re m o v e t h e f o r m i c a c i d .
U pon s t r i p p i n g o f f t h e s o l v e n t t h e r e r e m a i n e d 1 . 3 g ra m s o f a m a t e r i a l
t h a t w as n o t s o l u b l e i n b a s e .
A p p a r e n t l y t h e r e p e a t e d w a s h in g s
w i t h w a t e r a l s o re m o v e d t h e d e s i r e d p r o d u c t .
B. P r e p a r a tio n o f th e k e to -a ld e h y d e , 1 3 :
l)
z in c and a c e t i c
1 0 0 . 0 g ra m s (
g la c ia l a c e tic
a c i d r e d u c t i o n o f t h e o z o n id e
.7 3 3 m o le s ) o f d e l t a - 3 - c a r e n e i n 300 m l o f
a c i d a n d 18 m l o f e t h y l a c e t a t e w as s u b j e c t e d t o
-5 0 -
o z o n o ly s is a t 0*0.
A f t e r 1 0 h o u r s ( 6 . 2 g ra m s o z o n e p e r h p u r , t h e o -
r e t i e a l l y 1 .3 m o le s ),
w e re ad d e d t o t h e
lo w e d t o
700 m l e t h e r , 1 ^ 0 i)il ■w a t e r a n d 75 g ra m s z i n c
o z o n id e i n
a c e tic
a c i d a n d t h i s m i x t u r e w as a l -
s t i r m a g n e tic a lly o v e r n ig h t.
U pon f i l t r a t i o n
o f th e z in c
s a l t s , v a c u u m d i s t i l l a t i o n y i e l d e d U 0 .7 g ra m s ( 3 3 $ ) o f a p a l e g r e e n
liq u id .
2)
bp
9 2 -9 ® C
( l . 3 mm Hg)
d im e th y l s u l f i d e r e d u c tio n
I n t h i s m e th o d , t h e p r o c e d u r e o f S a s a t i a n d c o w o r k e r s w as
used.
6 8 . 0 g ra m s ( , 5 m o le s ) o f f r e s h l y d i s t i l l e d
c a r e n e i n 300 m l o f a b s o l u t e m q t h a n o l w as s u b j e c t e d t o
o z o n o ly s is
u n d e r c o o lin g w ith a d ry ic e - m e th a n o l b a th f o r 15 h o u r s ,
t h e b r o m i n a t i o n t e s t w as f o u n d n e g a t i v e .
d e lta -3 -
or u n til
A f t e r t h e r e a c t i o n w as
o v e r , n i t r o g e n g a s w as b u b b l e d i n t o t h e r e a c t i o n m i x t u r e f o r 5
.in i n u t e s a t t h e sam e t e m p e r a t u r e .
T h e n $2. m l (1+3-5 g r a m s ,
.7 m o le s )
o f d i m e t h y l s u l f i d e w e re a d d e d w i t h s t i r r i n g u n d e r t h e n i t r o g e n
a tm o s p h e re .
T h e r e a c t i o n t e m p e r a t u r e w as a l l o w e d t o r i s e
g ra d u a lly
t o ro o m t e m p e r a t u r e f i r s t b y c o o l i n g i n
a n i c e - s a l t b a t h f o r one
h o u r; th e n i n
and f i n a l l y
an i c e b a th f o r one h o u r;
a t u r e f o r one h o u r .
a t ro o m t e m p e r ­
T h e m e t h a n o l s o l u t i o n w as c o n c e n t r a t e d t o
1 0 0 m l a n d 5 0 0 m l o f b e n z e n e w as a d d e d .
T h e b e n z e n e s o l u t i o n w as
w a s h e d s e v e r a l t i m e s w i t h w a t e r , t h e n d r i e d ( s o d iu m s u l f a t e ) ,
t h e r e s i d u e t h a t re m a in e d b y re m o v a l o f t h e
and
s o l v e n t w as d i s t i l l e d
t o y i e l d 2 1 .6 g ra m s ( 2 6 $ ) o f a l i g h t y e l l o w o i l .
bp
9 U -9 6 0C
(U mm Hg)
P r e p a r a t i o n o f k o t o - a c i d , 16^ f r o m k e t o - a l d e h y d e , l £ : (
2 6 .0
g ra m s (
.1 5 5 m o le s ) o f t h e k e t o - a l d e h y d e ^
w i t h 2.00 m l a c e t o n e a n d 5 0 m l w a t e r a n d c o o l e d t o
s a l t b a th .
O0C w i t h a n i c e -
a t a tim e w ith c o n t r o l o f t e m p e r a t u r e b e tw e e n 5 -
IO 0G w h i l e b e i n g s t i r r e d m a g n e t i c a l l y .
o v e r n i g h t t h e MhO^ w as f i l t e r e d
h y d ro c h lo r ic a c id .
th e
1 5 , w a s 'm ix e d
22 g ra m s ( . l U m o le s ) o f p o t a s s i u m p e r m a n g a n a te w as
added a l i t t l e
s tirre d
)
The f i l t r a t e
■
'A f t e r th® r e a c t i o n m i x t u r e
•
o f f a n d d i s s o l v e d i n 10$
w as a l l o w e d t o e v a p o r a t e t o re m o v e
a c e t o n e a n d w as a d d e d t o t h e h y d r o c h l o r i c a c i d s o l u t i o n .
E x t r a c t i o n o f t h e c o m b in e d a q u e o u s s o l u t i o n s w i t h e t h e r ( 3 X 1 0 0 m l)
f o l l o w e d b y d r y i n g o v e r a n h y d r o u s s o d iu m s u l f a t e
an d vacuum d i s t i l ­
l a t i o n y i e l d e d 2 . 0 g ra m s ( 7 $ ) o f a b ro w n l i q u i d ,
bp
1 U 0-150°C
( 0 . 8 mm Hg)
P re p a ra tio n o f th e d ia c id , 1 7 :
2 , 9 g ra m s (
.0 1 5 8 m o le s ) o f t h e k o t o - a c i d , 1 6 , w a s m ix e d w i t h
I . 0 g ra m o f s o d iu m h y d r o x i d e a n d 1 0 m l w a t e r a n d c o o l e d t o
S o d iu m h y p o b r o m i t e w as p r e p a r e d - b y t h e
h y d ro x id e
O0C .
a d d i t i o n o f 9 . 0 g ra m s s o d iu m
( t o t a l f o r t h e r e a c t i o n w as 1 0 . 0 g ra m s ,. .2 5 m o le s ) t o
I I . 5 g ra m s ( .0 7 2 m o l e s ) o f b r o m in e a n d 1 5 0 m l w a t e r a n d t h e s o l u t i o n
-5 2 -
w as c p o l e d t o 0 * 0 .
When t h e t e m p e r a t u r e r e a c h e d 0*0 t h e s o d iu m
h y p o b r o m i t e w as a d d e d a l l a t o n c e a n d t h e s o l u t i o n w a s s t i r r e d
m a g n e t i c a l l y f o r I h o u r a t 0 -1 0 ° C , a n d f o r a n o t h e r 2 h o u r s a t 1 0 ro o m te m p e ra tu re .
E x c e s s s o d iu m h y p o b r o m i t e w as d e s t r o y e d b y a d d i ­
t i o n o f s o d iu m b i s u l f i t e
to
c o lo rle s s
).
( a c o l o r c h a n g e w as a p p a r e n t - l i g h t g r e e n
T h e r e s u l t i n g s o l u t i o n wp.s e x t r a c t e d w i t h e t h e r
t o re m o v e t h e b ro m o fo rm a n d t h e n a c i d i f i e d w i t h c o n c e n t r a t e d s u l ­
fu r ic
a c id t o
a pH o f 3 . 0 ( pH H y d r i o n p a p e r ) .
w a s s a t u r a t e d w i t h ammonium s u l f a t e
125 m l ) .
The a c id s o l u t io n
and e x tr a c te d w ith e th e r ( '3 X
T h e c o m b in e d f r a c t i o n s w e re, d r i e d o v e r a n h y d r o u s so d iu m
P if L f a t e 5 a n d u p o n e v a p o r a t i o n o f t h e e t h e r t h e p e r e m a i n e d .8 g ra m s
o f c r u d e d i a c i d t h a t w o u ld n o t c r y s t a l l i z e .
T h e 0 . 8 g ra m s o f
c r u d e d i a c i d w as c h r o m a t o g r a p h e d u s i n g B i o - S i l A ( 1 0 0 - 2 0 0 m esh ) .
as a s u p p o rt and c h lo ro fo rm as a s o l v e n t .
g ra m s ( l . 6 $ )
mp
o f p u re d ia c id .
T h i s m e th o d y i e l d e d
.1 8
R e c r y s t a l l i z e d fr o m e t h e r / h e x a n e .
1 1 2 -1 1 3 °C
A t t e m p t e d S c h m id t r e a c t i o n o n t h e d i a c i d , 1 7 :
T h e h y d r a z o i c a c i d w as p r e p a r e d b y t h e m e th o d o f W o l f f .
^ ^
A p a s t e w as m ade w i t h 1 0 . 0 g ra m s (» l5 U m o le s ) o f s o d iu m a z i d e a n d 1 0
m l w arm w a t e r .
0 0 .
T h i s w as a d d e d t o 6 0 m l o f b e n z e n e a n d c o o l e d . t o
7 .SU g ra m s ( . 0 8 m o l e s ) o f c o n c e n t r a t e d s u l f u r i c a c i d w as a d d e d
d r o p w ip e w i t h c o n t r o l o f t e m p e r a t u r e , n o t e x c e e d i n g 5 0 .
The o r -
-5>3-
g a n i c l a y e r w as s e p a r a t e d a n d d r i e d o v e r s o d iu m s u l f a t e .
. 2 . 3 g ra m s ( .0 1 2 m o le s ) o f t h e d i a c i d w as d i s s o l v e d i n 1 0 0
m l o f b e n z e n e a n d 20 m l o f c o n c e n t r a t e d s u l f u r i c
a c i d w as a d d e d .
W h ile s t i r r i n g m a g n e t i c a l l y a l l o f t h e h y d r a z o i c a c i d m ade ab o v e
w as a d d e d d r o p w i s e ( t h e t e m p e r a t u r e r e m a i n e d a t 3 3 ° C ),
A fte r ad­
d i t i o n o f h y d r a z o i c a c i d t h e r e a c t i o n m i x t u r e w as s t i r r e d u n t i l
gas e v o lu tio n had ce a se d .
in to w a te r.
T h e a c i d l a y e r w as s e p a r a t e d a n d p o u r e d
A s n o c r y s t a l s cam e o u t,, t h e w a t e r s o l u t i o n w as made
b a s i c b y a d d i t i o n o f s o d iu m h y d r o x i d e a n d e x t r a c t e d w i t h e t h e r .
T h e e t h e r l a y e r w a s d r i e d o v e r a n h y d r o u s s o d iu m s u l f a t e
e v a p o ra tio n y ie ld e d
of th is
„3 g ra m s o f a n a m in e .
am in e s u g g e s t e d i t t o b e a n i l i n e
a m id e d e r i v a t i v e
).
and upon
F u rth e r in v e s tig a tio n
( mp a n d nm r s p e c t r u m o f
No o t h e r p r o d u c t s w e re r e c o v e r e d .
P r e p a r a t i o n o f t h e d ia m in e h y d r o c h l o r i d e , 1 8 :
l.h
g ra m s (.0 0 7 3 m o le s ) o f t h e d i a c i d , 1 7 , w as s u s p e n d e d i n
3 m l w a t e r a n d s u f f i c i e n t a c e t o n e w as a d d e d f o r s o l u t i o n .
s o l u t i o n w as c o o l e d t o O1C i n
T h is
a n i c e - s a l t b a t h a n d 1 . 7 6 g ram s
( . 017U m o le s ) o f t r i e t h y l a m i n e i n 6 3 m l o f a c e t o n e w as a d d e d .
W h ile m a i n t a i n i n g t h e t e m p e r a t u r e a t O0G, 2 . 8 3 g ra m s ( . 0 1 9 2 m o le s )
o f e t h y l c h l o r o f o r m a t e i n 1 3 m l o f a c e t o n e w as a d d e d s l o w l y .
U pon
f i n a l a d d itio n o f th e e t h y l c h lo ro fo rm a te s o lu tio n t h e r e a c tio n
w as s t i r r e d m a g n e t i c a l l y f o r a n a d d i t i o n a l 30 m i n u t e s .
I . 76 g ra m s
( . 0 2 7 m o l e s ) o f s o d iu m a z i d e i n 1 0 m l o f w a t e r w as a d d e d d r o p w i s e ,
m a i n t a i n i n g t h e t e m p e r a t u r e a t O 'C .
A f te r f i n a l a d d itio n o f th e
s o d iu m a z i d e t h e r e a c t i o n m i x t u r e w as s t i r r e d f o r a n a d d i t i o n a l
h o u r a t O0C .
T h e n t h e r e a c t i o n m i x t u r e w as p o u r e d i n t o i c e f j a t e r
( 500 m l ) and e x tr a c te d w ith to lu e n e
( 3 Z ^O m l ) . T h e t o l u e n e
l a y e r s w e re c o m b in e d , d r i e d o v e r a n h y d r o u s m a g n e siu m s u l f a t e ,
t h e n h e a t e d u n t i l n o m o re n i t r o g e n w as e v o l v e d ( 1 0 0 ° C ) .
w as re m o v e d b y t h e r o t a r y e v a p o r a t o r y i e l d i n g
and
The to lu e n e
a m o b i le y e l l o w o i l .
T h i s y e l l o w o i l w as t h e n r e f l u x e d w iijh lj.0 m l o f 20$ h y d r o c h l o r i c
a c i d f o r 17 h o u r s .
T h e r e s u l t i n g d a r k s o l u t i o n w as c o o l e d a n d
w ash ed w ith e t h e r .
T h e a q u e o u s p o r t i o n w as e v a p o r a t e d u n d e r r e d u c e d
p re s s u r e y ie ld in g a d ark s e m i-s o lid .
T h i s m a t e r i a l w as d i s s o l v e d
i n m e t h a n o l a n d e t h e r w as a d d e d u n t i l a s o l i d c r y s t a l l i z e d o u t o f
s o lu tio n .
mp
F i l t r a t i o n y i e l d e d 1 . 0 g ra m s ( 6 6 $ ) o f a c o l o r l e s s s o l i d ,
g r e a t e r t h a n 300 °C
n m r:
( r e c r y s t a l l i z e d fro m m e t h a n o l/e th e r )
a d o u b l e t c e n t e r e d a t 1 . 2 d e l t a (8 H ) ; a m u l t i p l e t c e n t e r ­
e d a t 3 . 1 3 (1 |H ). ( c i s h y d r o g e n s a r e u n d e r t h e d o u b l e t )
P r e p a r a t i o n o f t h e q u a t e r n a r y ammonium i o d i d e , 1 9 :
1 .0
g ra m (
.0 0 3 m o le s ) o f t h e
a m in e h y d r o c h l o r i d e , 1 8 , i n
1 0 0 m l o f m e t h a n o l w as a d d e d t o - 2 0 g ra m s ( .1 4 m o l e s ) o f m e t h y l
io d id e .
T h i s s o l u t i o n w as m a g n e t i c a l l y s t i r r e d i n
an ic e b a th
d u r i n g t h e d r o p w i s e a d d i t i o n o f . 3 g ra m s (.0 1 2 3 m o l e s ) o f s o d iu m
h y d ro x id e i n 30 m l o f m e th a n o l.
A f t e r f i n a l a d d i t i o n o f so d iu m
h y d r o x i d e , t h e r e a c t i o n m i x t i r e w as s t i r r e d
a t O6C .
a n a d d i t i o n a l It h o u r s
T h e n .3 g ra m s m o re s o d iu m h y d r o x i d e w as a d d e d a n d t h e
r e a c t i o n m i x t u r e w as r e f l u x e d o v e r n i g h t u s i n g a n e f f i c i e n t c o n d e n s e r .
As t h e r e a c t i o n m i x t u r e c o o l e d , c r y s t a l s
cam e o u t o f s o l u t i o n a n d
u p o n f i l t r a t i o n y i e l d e d 2 . 1 g ra m s ( 9 0 $ ) o f a c o l o r l e s s s o l i d ,
mp
2 8 5 ~ 2 8 7 6C
n m r:
( r e c r y s t a l l i z e d fr o m m e t h a n o l )
A d o u b l e t c e n t e r e d , a t 1 . 3 1 d e l t a (8 H ) j a s i n g l e t a t
3 .2 3
(l8 H ) j a m u l t i p l e t c e n te r e d a t 3*9
(I)H)
P r e p a r a tio n o f l,l- d im e th y i- 2 ,3 - d im e th y le n e c y c lo p r o p a n e ,
?:
Two m e th o d s i n v o l v i n g t h e H ofm ann e l i m i n a t i o n w e re u s e d i n t h e ■
p y r o i y s i s o f t h e q u a t e r n a r y ammonium h y d r o x i d e , 2 0 .
I.
F o l l o w i n g t h e p r o c e d u r e o f W a it k u s a n d c o w o r k e r s
(3 3 )
T o 2 . 0 g ra m s (.OOlfB m o le s ) o f t h e q u a t e r n a r y ammonium i o d i d e ,
19,
i n 15> m l o f w a t e r w as s l o w l y a d d e d s i l v e r o x i d e , 'f r e s h l y p r e ­
p a r e d fr o m 9 » U g ra m s ( .0 3 5 m o le s ) o f s i l v e r n i t r a t e
(.O lfB m o le s ) o f s o d iu m h y d r o x i d e .
a n d 1 . 7 1 g ra m s
A fte r f i n a l a d d itio n o f th e s i l v e r
o x i d e , t h e m i x t u r e w as s t i r r e d f o r a n a d d i t i o n a l I4. h o u r s a t ro o m
.te m p e r a tu r e .
T he r e s u l t i n g m ix tu r e w as f i l t e r e d
s o l u t i o n w as t h e n s l o w l y ( a p p r o x .
a n d t h e r e m a i n in g
.2 m l / , m in . ) a d d e d t h r o u g h a
s e p tu m o n a 3 - n e c k f l a s k p r e h e a t e d t o
2 1 0 °C ."
T h e s y s t e m w as u n d e r
-5 6 -
a r e d u c e d p r e s s u r e o f lj..5 mm Hg ( n i t r o g e n ) „
A fte r f i n a l a d d itio n ,
t h e f l a s k ' w as h e a t e d a t 210*0 f o r a n a d d i t i o n a l 1 0 m i n u t e s .
The
p y r o l y s i s p r o d u c t s w e re t r a p p e d w i t h a d r y i c e / a c e t o n e h a t h .
2.
F o llo w in g t h e p ro c e d u re o f A rc h e r
T o 2 . 0 g ra m s (.O O lf? m o l e s ) o f t h e q u a t e r n a r y ammonium i o d i d e ,
1 9 , i n 15 m l o f w a t e r w as s l o w l y a d d e d s i l v e r o x i d e , ' f r e s h l y p r e ­
p a r e d f r o m 9 - U g ra m s ( .0 5 5 m o le s ) o f s i l v e r n i t r a t e
(.0143 m o le s ) o f s o d iu m h y d r o x i d e .
A f te r f i n a l a d d itio n o f th e
s i l v e r o x i d e , t h e m i x t u r e w as s t i r r e d
a t ro o m t e m p e r a t u r e .
f o r a n a d d i t i o n a l I4 h o u r s
T h e r e s u l t i n g m i x t u r e w as f i l t e r e d
r e m a i n i n g s o l u t i o n w as e v a p o r a t e d t o
p re ssu re .
a n d 1 . 7 1 g ra m s
and th e
d r y n e s s a t UO0C / w a te r-p u m p
U pon r e m o v a l o f t h e w a t e r t h e p r e s s u r e w as r e d u c e d t o
.1 5 mm Hg b y u s i n g a L a n g d o n v ac u u m pum p, a n d t h e t e m p e r a t u r e w as
s lo w ly r a i s e d t o
2 0 0 °C ,
a d ry i c e / a c e to n e b a th .
T h e p y r o l y s i s p r o d u c t s w e re t r a p p e d w i t h
T h i s p r o c e d u r e w as f o u n d t o b e s u p e r i o r
t o m e th o d I .
T h e s p e c t r a l d a t a w e re t h e n t a k e n a s f o l l o w s .
N u c le a r m a g n e tic r e s o n a n c e s p e c t r a :
I m l o f S ila n o r-C
(CDCl^ w i t h
1% TMS) w as a d d e d t o t h e f l a s k c o n t a i n i n g t h e p y r o l y s i s p r o d u c t s .
T h i s s o l u t i o n w as t h e n w a s h e d 2 t i m e s w i t h c o l d d i l u t e h y d r o c h l o r i c
a c i d a t O0C .
An nm r s p e c t r u m w as i m m e d i a t e l y r u n .
( r e s u lts in
-5 7 T a b le I I I )
U l t r a v i o l e t s p e c tr u m :
5 m l o f - h e x a n e w as a d d e d t o t h e f l a s k c o n ­
t a i n i n g th e p y r o l y s i s p ro d u c ts s t i l l
a t d ry ic e /a c e to n e te m p e ra tu re „
T h i s w as w a s h e d w i t h c o l d d i l u t e h y d r o c h l o r i c a c i d 2 t i m e s a n d
t h e n a n u l t r a v i o l e t s p e c t r u m w as i m m e d i a t e l y r u n ,
( r e s u l t s i n T a b le
II)
M ass s p e c t r u m :
2 m l o f c h l o r o f o r m w as a d d e d t o t h e p y r o l y s i s p r o ­
d u c t s a n d w as i n j e c t e d i n t o
a tta c h e d to
a g a s c h ro m a to g ra p h ,
a m a ss s p e c t r o m e t e r .
o p e r a t e d a t 70 °C,
T h e c o lu m n u s e d w as a 6 1 x
2 0 / c a rb o w a x o n c h r o m a s o r b - P . ( r e s u l t s i n T a b l e IV )
A t t e m p t e d D i e l s - A l d e r r e a c t i o n o n l , l - d i m e t h y l ~ 2 , 3 - d ± m e t h y 'l e n e c y c l o ~
p r o p sin e, 7 =
T h e I 3l - d i m e t h y l - 2 , 3 - d i m e t h y l e n e c y c l o p r o p a n e ,
as b e f o re fo llo w in g p ro c e d u re 2 .
7 , w as p r e p a r e d
T h e p y r o l y s i s p r o d u c t s w e re
d i s s o l v e d i n 5 m l o f a n h y d r o u s ■e t h e r ,
and t o t h i s
s o lu tio n ,
s till
a t d r y i c e / a c e t o n e t e m p e r a t u r e , w as a d d e d „2 g ra m s o f m a l e i c a n ­
h y d rid e i n 20 m l o f an h y d ro u s e t h e r .
A f t e r r e m a i n i n g a t t h a t te m ­
p e r a t u r e f o r 0 . 5 h o u r s , t h e s o l u t i o n w as p l a c e d i n
I h o u r,
a f t e r w h ic h t h e s o l u t i o n h a d t u r n e d c l o u d y .
an i c e b a th f o r
I t w as t h e n w arm ­
e d t o ro o m t e m p e r a t u r e f o r 0 . 5 h o u r s a n d t h e n w as p l a c e d i n a
f r e e z e r (~ 1 0 ° C ) o v e r n i g h t .
A p re c ip ita te
s o l u t i o n ( .0 5 g ra m s ) a n d u p o n f i l t r a t i o n
cam e o u t o f t h e e t h e r
and e v a p o r a tio n o f th e
-5 8 -
e t h e r t h e r e r e m a i n e d „19 g ra m s o f a s o l i d m a t e r i a l t h a t h a d a nm r
s p e c tru m i d e n t i c a l w ith t h a t o f m a le ic a n h y d r id e ,
7 .0 d e l t a
( one s i n g l e t a t
)
P r e p a r a tio n o f 1 ,1 ,2 ,3 - te tr a m e th y lc y c lo p r o p a n e ,
21:
I , l - d i m e t h y l - 2 , 3 - d i m e t h y l e n e c y c l o p r o p a n e w as p r e p a r e d b y u s i n g
p r o c e d u r e 2 a s d e s c r i b e d p r e v i o u s l y s t a r t i n g w i t h 2 . 0 g ra m s (.OOlg.3
m o le s ) o f t h e q u a t e r n a r y ammonium i o d i d e , 1 9 .
A fte r th e p y ro ly s is r e a c tio n ,
i m m e d i a t e l y 1 . 0 g ra m o f a c e t i c
a c i d i n 5 m l o f a b s o l u t e e t h a n o l w as a d d e d t p t h e p y r o l y s i s f l a s k
s till
a t d ry i c e / a c e to n e te m p e r a tu r e .
T o t h i s w as a d d e d a p r e ­
r e d u c e d m i x t u r e o f $0 mg o f 5% P d o n C i n 2 m l o f a b s o l u t e e t h a n o l
a n d t h e h y d r o g e n o l y s i s w as b e g u n a t a t m o s p h e r i c p r e s s u r e
a n d O0C .
T h e m a t e r i a l w as a g i t a t e d f o r If? m i n u t e s a t 0°C a n d t h e n ' p l a c e d
in
a w r i s t - a c t i o n s h a k e r f o r I h o u r a t U0C . . T h e h y d r o g e n o l y s i s
m i x t u r e w as t h e n f i l t e r e d
a n d t h e C a t p l y s t a n d s u p p o r t w e r e w a sh e d
w i t h a fe w m l o f a b s o l u t e e t h a n o l .
A g a s c h r o m a to g r a p h ( u s i n g a 1 0 ' %
p o lu m n p a c k e d w i t h 2 0 /
c a rb o w a x o n 3 0 /6 0 F i r e b r i c k ; c o lu m n w as r u n a t 3 0 ' C a n d a f?l m l / s e c
flo w r a t e )
o f t h e r e a c t i o n m ix tu r e r e v e a l e d one m a jo r p r o d u c t
( r e t e n t i o n t i m e - 3 „3 m i n u t e s ) a n d a m in o r p r o d u c t ( r e t e n t i o n t i m e 2 . 0 m i n u t e s ) t h a t w as n o t i d e n t i f i e d .
l e c t e d u s in g th e
T h e m a j o r p r o d u c t w as c o l ­
a b o v e c o lu m n a n d t h e d i f f e r e n t s p e c t r a l d a t a w e re
-
ru n .
T hose r e s u l t s
29-
a r e r e p o r t e d e l s e w h e r e . ' T h e m a ss s p e c t r u m
w as r u n u s i n g t h e sam e c o lu m n a s d e s c r i b e d . p r e v i o u s l y i n t a k i n g
t h e m a ss s p e c t r u m o f l , l - d i m e t h y l ~ 2 , 3 - d i m e t h y l e n e c y c l o p r o p a n e 5 J .
\
—
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