6 Pyrethroid-Like Esters of Cycloalkane Methanols and
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Some Reversed-Ester Pyrethroids M A L C O L M H. BLACK Wellcome Research Laboratories, High St., Berkhamsted, Hertfordshire, HP4 2DY, England
of
Two a s p e c t s of structure-activity s y n t h e t i c p y r e t h r o i d s are p r e s e n t e d
relationships in t h i s p a p e r .
P y r e t h r o i d - L i k e E s t e r s of Cycloalkane Methanols. A common f e a t u r e in t h e a l c o h o l i c components o f more effective pyrethroid esters (e.g. pyrethrin I , r e s m e t h r i n and p h e n o t h r i n ) is an u n s u b s t i t u t e d s i d e c h a i n s u p p o r t e d by a p l a n a r r i n g c o n t a i n i n g at l e a s t one olefinic bond. However, it has been c l a i m e d (1,2) t h a t an olefinic group can p l a y a similar r o l e t o the cyclic n u c l e u s ; f o r example
62
Elliott; Synthetic Pyrethroids ACS Symposium Series; American Chemical Society: Washington, DC, 1977.
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6.
B L A C K
Esters of Cycloalkane Methanols
63
1
as
II "frai 5 2 ; » II
O"^
II
PCS
β
«ο
o?
CUD
.Is
Elliott; Synthetic Pyrethroids ACS Symposium Series; American Chemical Society: Washington, DC, 1977.
β»
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64
SYNTHETIC PYRETHROIDS
4-aryl-trans-2-butene-1-yl chrysanthemates (I, R=R"=H, R'=Cl) have been shown t o be more effective against h o u s e f l i e s than allethrin (1). The c o r r e s p o n d i n g cis- b u t e n y l e s t e r s were not d e t e c t a b l y a c t i v e . It was, t h e r e f o r e , o f i n t e r e s t t o a s c e r t a i n whether the potency o f t h e t r a n s - b u t e n y l c h r y s a n t h e m a t e s c o u l d be r e t a i n e d w i t h o u t the olefinic bond, solely by p r o v i d i n g t h e a l c o h o l w i t h a rigid t r a n s arrangement o f b e n z y l and h y d r o x y m e t h y l g r o u p s . An indication t h a t such a result might be realised was s u g g e s t e d by a r e p o r t (3) t h a t the 4 - p h e n y l b u t y l c h r y s a n t h e m a t e , I I , was t w i c e as t o x i c t o h o u s e f l i e s as t h e 4 - p h e n y l - 2 - b u t e n y l chrysanthemate (I, R=R'=R"=H). Although surprising, such a result might be a t t r i b u t e d t o the p r e f e r e n c e o f t h e b u t y l e s t e r , I I , t o e x i s t in a transoid conformation. As t h e d e s i r e d s t r u c t u r a l f e a t u r e s are p r o v i d e d by s m a l l s a t u r a t e d c a r b o c y c l i c r i n g s , the c o r r e s p o n d i n g c i s and t r a n s - c y c l o p r o p y l , I I I a , b , and c y c l o b u t y l , I V a , b , analogues were examined. P r e p a r a t i o n o f Compounds. 4-Phenyl-2-butene~J~yl ( + ) - t r a n s - c h r y s a n t h e m a t e , I , was p r e p a r e d by t h e method of Sota e t a l . , ( . 1 ) , 4-phenyl-butyl (+)-trahis-chrysanthemate TlÎ]T"from t h e 4 - p h e n y l - b u t a n o l (4) and ( + ) - t r a n s c h r y s a n t h e m o y l c h l o r i d e and t h e c y c l o a l k y l m e t h y l ( + ) t r a n s - c h r y s a n t h e m a t e s I I I and IV as shown ( F i g u r e l ) . A n a l y t i c a l and s p e c t r a l d a t a were c o n s i s t e n t w i t h t h e proposed s t r u c t u r e s . R e s u l t s and D i s c u s s i o n . The a c t i v i t i e s f o r k i l l o f h o u s e f l i e s , a r e shown in T a b l e I. I n disagreement w i t h t h e r e p o r t (3,), t h e b u t y l e s t e r , I I , was o n l y one q u a r t e r as p o t e n t " a s t h e t r a n s - b u t e n y l e s t e r , I. T h i s r e s u l t c o u l d be a t t r i b u t e d t o d i f f e r e n t t e s t methods and s p e c i e s s u s c e p t i b i l i t y . Of t h e c y c l o a l k y l m e t h y l c h r y s a n t h e m a t e s , o n l y t h e t r a n s - c y c l o p r o p y l analogue, I l l b , showed d e t e c t a b l e a c t i v i t y , a p p r o x i m a t e l y h a l f t h a t o f t h e t r ans-buteny1 e s t e r , I , b u t s i g n i f i c a n t l y greater than the b u t y l e s t e r I I . I f the a c t i v i t y o f t h e t r a n s - c y c l o p r o p y l analogue depended upon t h e r i g i d t r a n s arrangement o f b e n z y l and h y d r o x y m e t h y l groups, t h e r e l a t e d t r a n s - c y c l o b u t y l analogue, IVb, would a l s o be e x p e c t e d t o be a c t i v e . S i n c e it was a c t u a l l y l e s s a c t i v e , t h e potency o f t h e t r a n s - c y c l o p r o p y l compound is p r o b a b l y a s s o c i a t e d w i t h t h e n a t u r e o f t h e c y c l o p r o p a n y l r i n g , t h e h y b r i d o r b i t a l s o f which, u n l i k e t h o s e o f c y c l o b u t a n e , can p r o v i d e it w i t h some o f t h e c h a r a c t e r i s t i c s o f an olefinic bond, a p p a r e n t l y necessary f o r u s e f u l a c t i v i t y w i t h i n t h i s s e r i e s o f
Elliott; Synthetic Pyrethroids ACS Symposium Series; American Chemical Society: Washington, DC, 1977.
6.
BLACK
Esters of
Cycloalkane
Methanoh
Table
chrys .O , C H -
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2
Compound
65
I.
X - CH 2
LD5O
X
γ/ο
Isomer Alone
I
-CH=CH
II
-CH2—
-
trans
CH2"
+P.B.(1:5)
Relative Potency Synergised
0.3
40
c.6.0
1.1
11
>6.0
>2.4
6.0
>2.4
6.0
>2.4
