4.2 DESARROLLO DE LOS MERCADOS INTERNO Y EXTERNO
4.2.6 Actividades por realizar
(1 1 3 ) RCH CH„CHCH(OH)R'A (115) (1 1 6 ) (114)
S u b s e q u e n tly , M ih a ilo v ic o t o x id is e d many p rim a ry and se c o n d a ry a l i p h a t i c a lc o h o ls , and some o y c lo a lk a n o ls , to 1 ,4 -^ p o x id e s i n y i e l d s o f 41-55% ,
S im ila r c y c l i s a t i o n p ro c e s s e s have b een o b se rv e d i n th e r e a c t i o n b etw een le a d t e t r a a c e t a t e and ox im es^^, and b etw een a lc o h o ls and le a d t e t r a a c o t a t e - i o d i n o ( th e s o - c a lle d
* h y p o io d ite r e a c t i o n * ) , ^^ M echanism o f th e r e a c t i o n ,
The i n i t i a l s te p i n th e r e a c tio n i s b e lie v e d to be th e r e v e r s i b l e fo rm a tio n o f a le a d a lk o x id e (1 1 7 ) from th e a lc o h o l and le a d t e t r a a c e t a t e : -
ROH + Pb(OAc^$ RO-Pb(OA.c)g| + AcOH
(1 1 7 )
# h e a lk o x id e (1 1 7 ) th e n u n d erg o es h e m o ly tic f i s s i o n to g iv e th e oxy**radical (1 1 8 ) w hich a b s t r a c t s a h y d ro g en atom from a d -c a rb o n fo rm in g th e r a d i c a l p a i r (1 1 9 ): -
« X ^ I . « X #
-P b -0 C ÿ -Pb* 0 C _ HO C *Pb-
’ 1__________I “ ’ I_______ I ‘
- 101
Tho r a d i c a l p a i r th e n u n d erg o es a one e l e c t r o n t r a n s f e r p ro c e s s g iv in g th e io n p a i r (120) w hich c y c l i s e s by th e lo s s o f a p ro to n to th e te tr a h y d r o f u r a n (121) : - j + f> HO Ç 'P b - —^ H -0 C P b - - 0 C P%)(OA.c) * * 1 i l * I I 4- 2 I I + AcOH V
J
(119) (120) (121) I t i s a ls o p o s s ib le f o r th e 03cy r a d i c a l (1 1 8 ) to a b s t r a c t h y d ro g e n from th o a c a rb o n th u s fo rm in g a c a rb o n y l compound (122) : - Ô o.1 J
H (1 1 0 ) (1 2 3 )I t was hoped t h e r e f o r e , t h a t m eth y l 9 and 12-h y d ro3cy- s t e a r a t e s w ould c y c l i s e i n t h i s m anner to g iv e m ix tu re s o f l,4 -e p 0 3 c id o s , B ra n d t and D je r a s s i^ ^ h av e a lr e a d y shown t h a t th e 9-h y d ro2c y e s te r f u r n is h e s a m ix tu re o f th e 6 ,9 and 9 ,1 2 - e p o x id e s , b u t th e y g iv e no i n d i c a t i o n o f y i e l d s n o r o f any o th e r p ro d u c ts form ed i n th e r e a c t i o n . S in c e i t was e x p e c te d t h a t 0]c o -e s te rs w ould accompany th e c y c lic e t h e r s , th e t o t a l p ro d u c t was t r e a t e d w ith sodium b o r o - h y d rid e p r i o r to prep,T L C , f o r th e two ty p e s o f compound h av e s im ila r % aolarity on s i l i c a g e l . The r e a c tio n s o f two u n s a tu r a te d e s t e r s ( 1 8 :1 , 120H,9c^ and 90H,12jc) and o f m eth y l
102 -
9 ,12- d ih y d r o x y s te a r a te w ere a ls o exam ined,
C y lis a tio n s w ith m e ta l o x id e -h a lo g o n r e a g e n ts .
I t h a s b een shown t h a t s t e r o i d a l a lc o h o ls can be co n v e r te d to 1, 4 -e p o x id e s by th e a c tio n o f e i t h e r m e rc u ric o x id e and i o d i n e o r s i l v e r ozcide and brom ine# I n th e s e m o le c u le s , th e r e a c t i v e c e n tr e s a r e f ix e d , b u t M ih ailo v ic^
95
e t a l , r e c e n t l y a p p lie d t h i s r e a c tio n to th e c y c l i s a t i o n o f open c h a in a lc o h o ls i n w hich th e above l i m i t a t i o n does n o t a p p ly . They o b ta in e d b e t t o r y i e l d s o f 1 , 4 -e p o x id e s th a n from th e c o rre s p o n d in g le a d t e t r a a c e t a t e r e a c t i o n s , and found t h a t th e o n ly o th e r p ro d u c t was th e c a rb o n y l com pound (122) .
Such o x id a tio n s w ere c a r r i e d o u t on th e two s a tu r a te d m onohydroxyooterc and on m eth y l 9 ,1 2 -d ih y d ro x j’^ s te a ra te
o n ly , s in c e i t was c o n s id e re d t h a t th o h a lo g e n w ould r e a c t w ith any o l e f i n i c c e n tr e i n th e m o le c u le .
DISCUSSION
M ethyl r i c i n o l e a t e and m eth y l 9 -h y d ro x y o c ta d e c - c l s - 12-e n o a te w ere p re p a re d a s d e s c rib e d p r e v io u s ly ( p ,4i) * The c o rre s p o n d in g s a tu r a t e d e s t e r s w ore o b ta in e d by h y d ro g e n a tio n o f th e o l e f i n i c com pounds. M ethyl # 9 ,12-d ih y d ro2cy' s t e a r a t e was p re p a re d by m é th y la tio n o f th o a c id (p , 1 3 9 ),
if 103 "i ,
R e a c tio n s w ith l e a d . t e t r a a c e t a t e , 1 . M ethyl 1 2 - h y d r o x y s te a r a te .
The h y d r o x y e s te r was r e f lu x e d f o r 20 h o u rs w ith le a d * t e t r a a c e t a t e i n b en zen e s o l u t i o n . The t o t a l r e a c t i o n p ro d u c t was exam ined on GLC ( t a b l e 33) and TLC,
TABLE 33, ECLs(DEGS) ECLs(ApL) 1 6 .3 1 3 .7 (5%) 2 0 .3 1 7 ,8 (3%) 2 1 .3 2 1 .6 1 8 .6 (72%) 2 1 ,9 2 4 .8 (o x o ) 1 9 ,3 (3%) 2 5 .9 (h y d ro x y ) 1 9 ,8 (17%) 2 7 .6 2 8 ,2
A f te r r e d u c tio n w ith sodium b o ro h y d rid e , prep.TLC o f th e p ro d u c t a f f o r d e d f o u r f r a c t i o n s : - A (7% ), B (59% ), C (17%) and D (17% ).
F r a c tio n D. (17%)
T h is f r a c t i o n gave no p eak s on GLC e i t h e r b e f o r e o r a f t e r t r i m e t h y l s i l y a t i o n . TLC e x a m in a tio n showed th r e e a p o ts o f low v a lu e . The m ix tu re was n o t i n v e s t i g a t e d f u r t h e r .
— 104 —
F r a c tio n C (17% ).
T h is band c o n s is te d o f m eth y l 1 2 - h y d ro x y s te a ra te (05% ), [ECLs (DEGS) o f 25*9 and 1 9 .6 b e f o re and a f t e r t r i m e t h y l s i l y l a t i o n ] . Of t h i s t o t a l , '%2% was due to u n ro a c te d s t a r t i n g m a te r ia l and 13% came from r e d u c tio n o f th e 12—o x o - e s te r . A lso p r e s e n t i n t h i s f r a c t i o n w ere th e com ponents o f ECLs
(DEGS) 2 7 .6 and 2 0 .2 (15% ), r e p r e s e n tin g p ro d u c ts w hich c o u ld n o t bo i s o l a t e d and i d e n t i f i e d .
F r a c tio n A (7% ).
GLC e x a m in a tio n o f t h i s f r a c t i o n in d ic a te d t h a t i t was a com plex m ix tu re o f s h o r t c h a in e s t e r s . The m ajo r com ponents h ad ECLs o f 1 6 .3 and 2 0 .3 (DEGS), and 1 3 ,7 and 1 7 .8 (ApL)
and w ere accom paniod by s e v e r a l m inor p r o d u c ts . T h is band th e r e f o r e c o n s is t s o f v a r io u s c le a v a g e p ro d u c ts and was n o t exam ined f u r t h e r .
F r a c tio n B (59% ).
As th e m ajo r p ro d u c t o f th e r e a c t i o n , f r a c t i o n B
a t t r a c t e d m ost a t t e n t i o n . I t was r e a d i l y shown by GLC and MS to b e a m ix tu re o f th e m ethyl 9 ,1 2 and 1 2 ,1 5 - e p o x y s te a r
a te s (1 2 3 ) and (1 2 4 ). F r a c tio n B had ECLs o f 2 1 .3 , 2 1 .6 and 2 1 .9 (DEGS), and gave a b ro a d p eak o f ECL 1 8 .6 (A pL). The m ass s p e c t r a l e v id e n c e in d ic a te d an a p p ro x im a te ly e q u a l m ix tu re o f th o two 1 ,4 -e p x o id e s and th e m ajo r p e a k s i n th o
s. a -3 2 b b -1 0 N ote, - 105 •!- TABLE 34, (CH ) CO CH » la 5 , n = 7; (123) 2, n 5= 1 0 X 1 2 4 ) 227 (3 0 ) 195 (3 1 ) 200 (5 ) 155 (7 5 ) 137 (7 ) 1 2 ,1 5 269 (2 1 ) 237 (1 0 ) 242 (7 ) 113 (5 4 ) 95 (1 0 0 ) The p re s e n c e o f th e same q u a n t i t i e s o f b o th th e 9 ,1 2 and 1 2 ,1 5 iso m e rs in d ic a te d t h a t t h e r e was no
p ro fe r e n c e f o r h y d ro g en a b s tr a c t i o n a t 0 (9 ) o r 0 (1 2 ) i n th e c h a in .
2 . M ethyl 0- h y d r o x y s te a r a te .
The p ro d u c t d e r iv e d from t h i s e s t e r y ie ld e d e s s e n t i a l l y th e same f r a c t i o n s a s th e 1 2 -h y d ro x y e s te r a f t e r r e d u c tio n and prep.T L C , T h ese w e r e :- A (8%, c le a v a g e p r o d u c ts ) ; B (60%, l,4 * -o p o K id es)J C (15%, m ethyl Q -h y d ro x y s to a ra to and unlm owns) and D (17%, p o la r m a t e r i a l ) .
F r a c tio n B (60% ).
C a r e f u l s e p a r a tio n o f B by p re p . TLC u s in g d o u b le d ev elo p m en t y ie ld e d two sub f r a c t i o n s ; B_ (47%) and
- 106 -*•
(53%)* Of t h e s e , th e l e s s p o la r hand was shown by GLC and MS to ho m eth y l 9 ,1 2 - e p o x y s te a r a te , Tho more p o la r f r a c t i o n a ls o h ad ECLs o f 2 1 .3 and 2 1 .7 (DEGS), and 1 8 ,^ (A pL), w h ils t th o m ass s p e c t r a l e v id e n c e i n d ic a te d t h a t i t was m eth y l 6 , 9 - e p o x y s te a r a te (1 2 5 ). The m a jo r p eak s i n th e m ass sp e c tru m o f a r e shown i n t a b l e 35.
(125)
a a -3 2 a -5 0 c b b -1 8
135 (100) 153 (7 7 ) 135 (2 3 ) 150 (5 8 ) 197 (5 0 ) 179 (9 ) The r e a c tio n s o f th e two s a tu r a te d h y d ro x y © ste rs th e r e f o r e gave th e e x p e c te d 1 ,4 -e p o x id e s (00%) and th e p ro d u c ts o b ta in e d from each a r e sum m arised i n t a b l e 36.
ta ble 36. P ro d u c t 1 8 :0 . 12QH 1 8 :0 , 90H