Overview of Agrochemical Development - ACS Publications

Chapter 1 Overview of Agrochemical Development 1

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Don R. Baker , Joseph G. Fenyes , William K. Moberg , and Barrington Cross 4

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ICI Americas Inc., 1200 South 47th Street, Richmond, CA 94804 Buckman Laboratories, 1256 North McLean Boulevard, Memphis, TN 38108 Agricultural Products Department, E. I. du Pont de Nemours & Co., Experimental Station, Building 402, Wilmington, DE 19898 Agricultural Research Division, American Cyanamid Company, P.O. Box 400, Princeton, NJ 08540 2

Downloaded by UNIV OF SUSSEX on May 9, 2016 | http://pubs.acs.org Publication Date: November 3, 1987 | doi: 10.1021/bk-1987-0355.ch001

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Since the earliest of recorded time, man has fought with the environment in tilling his f i e l d s . At f i r s t largely by hand, then with the hoe, and later the plow. First with the aid of animals, later with machinery. Chemicals too, gradually found a place in providing a suitable environment. The Romans used salt to remove unwanted vegetation, and sulfur was used to control a variety of pests. The dawn of the twentieth century saw many inorganic compounds being used as agrochemicals. Then, the 1940's saw the coming of the f i r s t generation of synthetic organic agrochemicals including DDT (1), 2,4-D (2), and parathion (3). As technology advances, each step brings certain blessings and often unexpected problems. Such was the case with the f i r s t generation of organic agrochemicals. The farmer's yields were greater and costs were lower. But the f i r s t generation compounds did not solve a l l of the problems. DDT was too persistent and had an adverse effect on some species of wildlife (4-5). There was accumulation in the food chain, thin eggshells, and genetic effects in some species. Because of these various health and environmental concerns, DDT became embroiled in controversy (67). Parathion was too toxic for the average home gardener, indeed, it was too toxic for the average farmer. Even a fine herbicide like 2,4-D had its limitations. It is primarily active on broadleaf plants. This makes it fine for some weeds in small grains and grasses, but useless for broadleaf crops. Here was a need for later generations of herbicides. As 2,4-D controlled the broadleaf weeds, the resistant weeds such as wild oats (Avena fatua), Johnsongrass (Sorghum halepense), and 0097-6156/87/0355-0001$06.00/0 © 1987 American Chemical Society

Baker et al.; Synthesis and Chemistry of Agrochemicals ACS Symposium Series; American Chemical Society: Washington, DC, 1987.


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SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS

f o x t a i l s ( S e t a r i a s p . ) became p r o b l e m s i n t h e U n i t e d States. I n E u r o p e t h e p r o b l e m weeds were t h e c l e a v e r s ( G a l i u m sp .) , c h i c k w e e d ( S t e 1 1 a r i a s p , ) , b l a c k g r a s s ( A l o p e c u r u s m y o s u r o i d e s ) , and w i l d o a t s . Wild oats became such a p r o b l e m i n E u r o p e t h a t c o n t r o l of t h i s s i n g l e weed was i n c e n t i v e e n o u g h t o d e v e l o p h e r b i c i d e s solely for i t s control. Compounds s u c h as d i c l o f o p m e t h y l ( j i ) , d i f e n z o q u a t ( 9 0 » a n d f l a m p r o p (10.) w e r e d e v e l o p e d t o meet t h i s n e e d . The m e t a l l i c f u n g i c i d e s u s e d i n t h e f i r s t h a l f o f t h e t w e n t i e t h c e n t u r y w e r e l a r g e l y r e p l a c e d by t h e p r o t e c t i v e f u n g i c i d e s s u c h a s c a p t a n ( 1 1 - 1 2 ) a n d l a t e r t h e new s y s t e m i c s such as benomyl ( 1 3 ) . G r a d u a l l y the unwanted side e f f e c t s of t h e s e f i r s t g e n e r a t i o n a g r o c h e m i c a l s made i t a p p a r e n t t h a t a s u c c e s s f u l a g r o c h e m i c a l must have t h e p r o p e r e n v i r o n m e n t a l , t o x i c o l o g i c a l , and c o s t c h a r a c t e r i s t i c s i n addition to i t s basic useful a c t i o n . Each of t h e s e g e n e r a l r e q u i r e m e n t s h a s s e v e r a l c r i t e r i a t h a t m u s t be s a t i s f i e d b e f o r e a p a r t i c u l a r compound i s c o m m e r c i a l i z e d (]A_) . T e n s o f t h o u s a n d s o f c o m p o u n d s m u s t be p r e p a r e d a n d t e s t e d b e f o r e one i s f o u n d t h a t has a s u i t a b l e c o m b i n a t i o n of p r o p e r t i e s t h a t w i l l w a r r a n t c o m m e r c i a l development. S i n c e t h e c o s t o f g e n e r a t i n g a n y new p r o d u c t i s s t a g g e r ing, o n l y p r o d u c t s t a r g e t e d t o w a r d m a r k e t s w h i c h have a high p o t e n t i a l f o r p r o f i t are developed. A negative side e f f e c t of t h i s process i s that chemicals f o r minor crop m a r k e t s a r e o f t e n i g n o r e d . T h e r e f o r e , any p r o c e s s t h a t c a n l e s s e n t h e number o f compounds p r e p a r e d and t e s t e d b e f o r e a commercial product i s found i s of major importance. The q u e s t i o n i s o f t e n a s k e d , "How do y o u d i s c o v e r a new agrochemical?" The r a n d o m s y n t h e s i s and s c r e e n i n g m e t h o d gave us t h e f i r s t g e n e r a t i o n o f a g r o c h e m i c a l s . As we h a v e s e e n , however, t h e s e compounds were not w i t h o u t t h e i r problems. The n e x t s u c c e s s f u l a p p r o a c h i s e x e m p l i f i e d by the organophosphate insecticides. Here t h e d i m e t h y l o r d i e t h y l d i t h i o p h o s p h a t e g r o u p was a t t a c h e d t o j u s t a b o u t any t y p e o f a v a i l a b l e b u i l d i n g b l o c k . This approach was l a t e r extended t o i n c l u d e the phosphonate analogs. T h r o u g h a c o m p a r i s o n o f t h e i n s e c t i c i d a l and toxicological d a t a , s t r u c t u r e - a c t i v i t y t h e o r i e s were d e v e l o p e d which p r o v i d e d a means f o r t h e s y n t h e s i s o f s a f e r c o m p o u n d s . A s i m i l a r a p p r o a c h was u s e d i n t h e 2,4-D area. A l l manner of s u b s t i t u t e d phenoxy and b e n z o i c a c i d s and t h e i r d e r i v a t i v e s were p r e p a r e d . As a r e s u l t , m u c h was l e a r n e d about t h e s t r u c t u r a l r e l a t i o n s h i p s f o r t h e a u x i n t y p e action. T h i s a n a l o g s y n t h e s i s p r o c e d u r e has o f t e n been c a l l e d "me t o o c h e m i s t r y " . The p a t e n t l i t e r a t u r e a b o u n d s w i t h e x a m p l e s o f s u c h a s t r a t e g y t r i e d on a l m o s t e v e r y t h i n g t h a t has shown a m o d i c u m o f b i o l o g i c a l a c t i v i t y . J u s t a s 2,4-D i s a mimic of n a t u r a l a u x i n , most c r i t i c a l natural products p e c u l i a r l y associated with plants, i n s e c t s o r m i c r o o r g a n i s m s have been s t u d i e a w i t h a wide v a r i e t y o f m i m i c s , and a n a l o g s . Now i t i s a common


1. BAKER ETAL.

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Overview of Agrochemical Development


p r a c t i c e f o r r e s e a r c h o r g a n i z a t i o n s t o do t h e i r own "me too c h e m i s t r y " on t h e i r p r o m i s i n g compounds. The " * r p o s e of t h i s a p p r o a c h i s t o f u l l y u n d e r s t a n d t h e s t r u c t u r e a c t i v i t y r e l a t i o n s h i p s o f t h o s e new compounds b e f o r e t h e s c i e n t i f i c community a t l a r g e becomes aware o f t h e i r s i g n i f i c a n c e , p r i m a r i l y t o s o l i d i f y and d e f e n d p r i m a r y patent p o s i t i o n s . A n o t h e r i n t e r e s t i n g a p p r o a c h i s t h e d e s i g n o f new compounds t h a t i n t e r a c t w i t h a c r i t i c a l enzyme o f interest. T h i s s t r a t e g y has been f r u i t f u l i n pharmaceuti c a l r e s e a r c h , r e s u l t i n g i n major compounds such a s cimetidine. Some have l a b e l e d t h i s s t r a t e g y as b i o c h e m i cal design. The same s t r a t e g y i s i n d e e d p o s s i b l e i n t h e agrochemical area. As y e t we know o f no c o m m e r c i a l a g r o c h e m i c a l s t h a t have come by t h i s r o u t e ; b u t , t h i s i s none the l e s s a f l o u r i s h i n g a r e a f o r c u r r e n t r e s e a r c h (.150 • A c u r r e n t example i s t h e u s e o f b i o i s o s t e r e s • Agrochemical d i s c o v e r y g r o u p s a l s o employ t e c h n i q u e s such as q u a n t i t a t i v e s t r u c t u r e - a c t i v i t y r e l a t i o n s h i p s (QSAR) as e x e m p l i f i e d by t h e s t r a t e g y o f C o r w i n Hansch ( 1 6 ) . Related t o t h i s approach i s t h e use of m o l e c u l a r modeling and computer a i d e d s y n t h e t i c d e s i g n (1.7.) • T h e s e new t o o l s p r o m i s e t o y i e l d i n t e r e s t i n g new compounds w h i c h may someday f i n d c o m m e r c i a l u s e . To d a t e , t h e g r e a t e s t d e g r e e o f s u c c e s s has come as a consequence of o p p o r t u n i t y . Some, f o r want o f a b e t t e r l a b e l , have c a l l e d i t s e r e n d i p i t y (.18) . However, i n a r e a l sense i t i s much more t h a n l u c k . Usually t h i s takes the f o r m o f someone r e c o g n i z i n g an u n u s u a l r e s u l t . Many i n d i v i d u a l s s e e i n g t h e same e v e n t may not have t h e r e q u i r ed i n s i g h t . The u n e x p e c t e d r e s u l t may be one compound out o f a group o f compounds, which f o r some unknown r e a s o n , has u n u s u a l p r o p e r t i e s o r c h a r a c t e r i s t i c s when compared with others i n the group. I t may be a compound t h a t has c h e m i c a l l y o r m e t a b o l i c a l l y changed i n t o a n o t h e r compound which i s strangely a c t i v e . I t may be an i m p u r i t y i n an o t h e r w i s e i n a c t i v e compound. I t may be an i n t e r m e d i a t e on the path t o p r e p a r a t i o n o f a n o t h e r m a t e r i a l . I t may be t h a t a c r e a t i v e new s c r e e n i n g t e s t shows a c t i v i t y f o r a seamingly i n a c t i v e m a t e r i a l . I t c e r t a i n l y pays t o keep alert. B e n j a m i n F r a n k l i n p e r h a p s s a i d i t b e s t when he r e m a r k e d , "The h a r d e r I work, t h e l u c k i e r I get. " 1

Herbicides The b a s i c i d e a b e h i n d t h e e a r l y h e r b i c i d e s was t h a t you s p r a y e d a group o f p l a n t s w i t h a compound and t h e weeds were k i l l e d l e a v i n g t h e c r o p unharmed. T h i s type of compound has come t o be known as a p o s t - e m e r g e n t herbicide. F a i r l y q u i c k l y , i t was f o u n d t h a t f o r c e r t a i n c r o p s such as c o r n , c o t t o n , and s o y b e a n s , i t was h a r d t o f i n d compounds t h a t k i l l e d t h e weeds w i t h o u t i n j u r y t o t h e



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crop. The s e c o n d g e n e r a t i o n o f h e r b i c i d e s i n c l u d e d t h o s e t h a t r e q u i r e d a p p l i c a t i o n t o t h e s o i l before t h e crop and weeds emerged. I n t h i s way many o f t h e t r o u b l e s o m e w e e d s c o u l d be e l i m i n a t e d i n s e l e c t i v e c r o p s . I n c l u d e d were compounds s u c h as t h e t r i f l u r a l i n , a t r a z i n e , and t h e chloracetamide herbicides. H e r e t h e f a r m e r had t o be convinced t o s p r a y h i s f i e l d b e f o r e t h e c r o p a n d weeds emerged. F o r some h e r b i c i d e s , maximum a c t i v i t y r e q u i r e d a v a r i a t i o n o f t h i s pre-emergent s u r f a c e a p p l i c a t i o n method. T r i f l u r a l i n s u f f e r s from l i g h t i n s t a b i l i t y and high volatility. I t was f o u n d t h a t s h a l l o w i n c o r p o r a t i o n i n the s o i l g r e a t l y a i d s i t s h e r b i c i d a l e f f e c t . Incorpora t i o n (_1S0 was a b s o l u t e l y e s s e n t i a l f o r t h e h e r b i c i d a l action of the thiolcarbamate (2j0) h e r b i c i d e s because of their volatile nature. W i t h t h e a d v e n t o f t h e s e s e c o n d g e n e r a t i o n c o m p o u n d s came t h e f i n d i n g t h a t many d i f f e r e n t s t e p s i n t h e p l a n t ' s biochemistry are susceptible to chemical e x p l o i t a t i o n (212 8). Those pathways t h a t a r e d i f f e r e n t from other forms o f l i f e a r e p r i m e t a r g e t s f o r a t t a c k i n t h e d e s i g n o f new a g r o c h e m i c a l s (J30). T o x i c o l o g i c a l l y s a f e r c o m p o u n d s a r e m o r e l i k e l y t o be f o u n d b y t h i s a p p r o a c h . The f i r s t c h a p t e r i n t h e h e r b i c i d e s e c t i o n i s d e v o t e d t o s y n t h e t i c e f f o r t s r e l a t e d t o t h e h e r b i c i d e Command, c u r r e n t l y b e i n g d e v e l o p e d b y FMC C o r p o r a t i o n . H e r e we s e e d e t a i l e d t h e v a r i o u s s y n t h e t i c ands t r u c t u r e - a c t i v i t y r e l a t i o n s h i p s o f t h i s i m p o r t a n t group o f compounds. These compounds e x e r t t h e i r p h y t o t o x i c e f f e c t by t h e i r bleaching a c t i o n on a w i d e v a r i e t y o f e c o n o m i c w e e d s . An important o b s e r v a t i o n was t h a t s o y b e a n s w e r e n o t a f f e c t e d a t n o r m a l use r a t e s . These compounds a c t upon t h e c a r o t e n e and chlorophyll biosynthesis of the plant. Here a r e a group of s y n t h e t i c pathways t h a t a r e p e c u l i a r t o p l a n t s and a few m i c r o o r g a n i s m s a n d a r e s u s c e p t i b l e t o c h e m i c a l attack. This spectacular bleaching e f f e c t i s discussed i n other c h a p t e r s o f t h i s work, such as t h e N - b e n z y l i d e n e a m i n o heterocycles of t h e S h e l l workers, the nicotinamides of S t a u f f e r , t h e p y r i d a z i n e s o f American Cyanamid and t h e furanones o f Chevron. Various aspects of carotenoid b i o s y n t h e s i s i n h i b i t i o n have been p r e s e n t e d i n other p l a c e s (27,31) » h o w e v e r , we s e e h e r e some o f t h e e x c i t i n g new c h e m i s t r y a s s o c i a t e d w i t h t h e s e p o w e r f u l compounds. The d i s c o v e r y p r o c e s s f o r Dow's T a n d e m h e r b i c i d e a n d t h e s y n t h e s i s d e t a i l s a s s o c i a t e d w i t h t h e h u n d r e d s o f new compounds p r e p a r e d d u r i n g t h e d i s c o v e r y p r o c e s s o f t h i s i n t e r e s t i n g new h e r b i c i d e a r e d e s c r i b e d i n a n o t h e r chapter. The f i n d i n g i n f i e l d t e s t s t h a t T r i d i p h a n e and A t r a z i n e were s y n e r g i s t i c i s an example o f o p p o r t u n i t y p r e s e n t i n g i t s e l f a n d an aware b i o l o g i s t r e c o g n i z i n g t h e s i g n i f i c a n c e o f t h e phenomenon.


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BAKER ET AL.

Overview of Agrochemical Development

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The w o r k e r s a t A m e r i c a n C y a n a m i d p r e s e n t some o f the s y n t h e t i c and b i o l o g i c a l c h a r a c t e r i s t i c s o f t h e s u l f u r analogs of t h e i r i m i d a z o l i n e f a m i l y of h e r b i c i d e s . This i s an e x a m p l e o f r e p l a c i n g t h e c a r b o n y l o f t h e i m i d a z o l i n o n e w i t h an i s o s t e r i c m o i e t y . T h i s i s an i n t e r e s t i n g a c c o u n t of t h e s y n t h e s i s and s t r u c t u r e - a c t i v i t y r e l a t i o n s h i p s i n a v e r y a c t i v e s e r i e s of herbicides. O t h e r i n t e r e s t i n g new c h e m i s t r y u s i n g b i o i s o s t e r e s i s presented i n the benzylnitramines of American Cyanamid, the v i n y l o g o u s u r e a s of S t a u f f e r , the t e t r a h y d r o f u r a n e s of C h e v r o n , a n d t r i a z i n o n e s o f FMC. The n i t r a m i n e s of t h i s c u r r e n t e x a m p l e seem t o f u n c t i o n a s a b i o i s o s t e r e o f a carboxylic acid. The v i n y l o g o u s u r e a s a r e a n o t h e r e x a m p l e of a p o s s i b l e homologous b i o i s o s t e r e at work. And f i n a l l y , t h e t r i a z i n o n e s a p p e a r t o b e h a v e as i m i d e bioisosteres. These c e r t a i n l y are concepts which m e r i t wider attention. The s t u d i e s d e v o t e d t o t h e n a t u r a l herbicide, cyanobacterin, a n d t h e r i g i d p e p t i d e r e p o r t e d by t h e USDA w o r k e r s show h e r b i c i d a l e f f e c t s a n d g i v e i n s i g h t i n t o t h e p o t e n t i a l geometry or f i t f o r o t h e r a c t i v e compounds t h a t have t h e d e s i r e d s p a t i a l and e l e c t r o n i c c h a r a c t e r i s t i c s . Insecticides P r i o r t o t h e a d v e n t o f DDT and t h e o r g a n o p h o s p h a t e s , t h e n a t u r a l p y r e t h r i n s ( 3 2 , 3 3 ) f o u n d c o n s i d e r a b l e use but were l i m i t e d by t h e i r i n s t a b i l i t y . The d i s c o v e r y o f p e r m e t h r i n b y M i c h a e l E l l i o t (34^) p r o v e d a t u r n i n g p o i n t f o r t h e new synthetic pyrethroids. Here were v e r y a c t i v e compounds t h a t d i d not s u f f e r from the s t a b i l i t y problems of the n a t u r a l compounds. And e v e n now p y r e t h r o i d - l i k e compounds c o n t i n u e t o i n t e r e s t s y n t h e t i c c h e m i s t s due t o t h e i r h i g h i n s e c t i c i d a l a c t i v i t y and r e l a t i v e l y low mammalian toxicity. Y o u w o u l d t h i n k t h a t by now m o s t o f t h e v e r y a c t i v e compounds w o u l d have been f o u n d . B u t i t seems t h a t p e r s i s t e n c e a n d o r i g i n a l i t y pay o f f . W o r k e r s a t du P o n t and FMC d e t a i l the s t r u c t u r e - a c t i v i t y r e l a t i o n s h i p s f o r two g r o u p s o f new p y r e t h r o i d - l i k e compounds. Chemists at Dow r e v e a l some o f t h e i n t r i c a c i e s i n t h e s y n t h e s i s o f the cyclopropane carboxylate end o f t h e m o l e c u l e . C a r b a m a t e s a n d p h o s p h a t e s c o n t i n u e t o be made by c h e m i s t s the world over. Amazingly, they continue to f i n d very active materials. C h e m i s t s a t S h e l l and a t Ricerca describe t h e i r e f f o r t s with t h i s active area. Other i n t e r e s t i n g t y p e s of a c t i v e compounds such as the oxadiazoles and d i a z e n e c a r b o x a m i d e s a r e a l s o described. E v e n c o m p o u n d s r e l a t e d t o DDT (35) a r e of i n t e r e s t . Iowa S t a t e w o r k e r s d e s c r i b e some diphenylchloronitroalkane compounds and t h e i r s y n t h e s i s and b i o l o g i c a l p r o p e r t i e s .



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T h e s e new c o m p o u n d s o f f e r t h e p o s s i b i l i t y o f l e s s p e r s i s t a n c e t h a n DDT• Many a r e q u i t e a c t i v e . USDA c h e m i s t s have f o u n d t h a t p e r f l u o r i n a t e d s u l f o n a m i d e s s u l f o n a t e s h a v e a d e l a y e d a c t i o n on t h e f i r e a n t .

and

N a t u r a l p r o d u c t s s u c h as t h e a v e r m e c t i n s and milbemycin produce very a c t i v e i n s e c t i c i d e s . Chemistry i n t h i s area i s p r e s e n t e d i n one c h a p t e r . J u v e n i l e hormone a c t i v i t y ( 36 ) s t i l l i s o f i n t e r e s t , a n d c u r r e n t w o r k i s d e s c r i b e d in this f i e l d .


Fungicides A d v a n c e s i n f u n g i c i d e c h e m i s t r y were r e c e n t l y reviewed (3_7) • Recent f u n g i c i d e r e s e a r c h p o i n t s out a f a c t o r common t o a l l a r e a s « the growing problem of pest resistance (38-39). S i n c e b a c t e r i a a n d f u n g i c a n go through t h e i r l i f e c y c l e q u i t e r a p i d l y , r e s i s t a n c e to a c o n t r o l agent can d e v e l o p r a p i d l y . This i s p a r t i c u l a r l y t r u e i f t h e compound a f f e c t s o n l y one b i o c h e m i c a l t a r g e t s i t e i n the pest. T o d a y we a r e s e e i n g r e s i s t a n c e d e v e l o p t o many o f o u r m o s t u s e f u l f u n g i c i d e s , w h i c h a g a i n p o i n t s o u t t h e p r e s s i n g n e e d t o f i n d new products. F u n g i c i d e r e s e a r c h r e c e i v e s l e s s a t t e n t i o n by s y n t h e s i s c h e m i s t s i n t h e U n i t e d S t a t e s t h a n do t h e h e r b i c i d e a n d insecticide disciplines. O v e r s e a s c h e m i s t s f i n d a much g r e a t e r m a r k e t f o r f u n g i c i d e s t h a n do t h e i r A m e r i c a n counterparts. One o f t h e c h a p t e r s i n d i c a t e s t h e i n t e r e s t o f t h e J a p a n e s e i n f u n g i c i d e s . Two c h a p t e r s a t t e s t t o England's c o n t r i b u t i o n s t o f u n g i c i d e chemistry. These ergosterol biosynthesis i n h i b i t o r s continue to a t t r a c t e f f o r t f r o m a r o u n d t h e w o r l d as e v i d e n c e d by t h e s e workers and t h e r e p o r t s f r o m A m e r i c a n a u t h o r s . O r g a n o s i l i c o n c o m p o u n d s seem t o have f o u n d a n i c h e i n fungicides. I n t e r e s t i n g c h e m i s t r y and t h e b i o l o g i c a l r e s p o n s e t o i t i s d e s c r i b e d f o r a new o g a n o s i l i c o n fungicide. L a e t i s a r i c a c i d , a h y d r o x y l a t e d f a t t y a c i d i s o l a t e d from s o i l fungus, i s d e s c r i b e d . Its structure-activity r e l a t i o n s h i p s l e d t o t h e d e s i g n o f e v e n more a c t i v e and s i m p l e r compounds. T h i s example p r o v i d e s another i l l u s t r a t i o n o f t h e v a l u e o f n a t u r a l compounds and t h e v a l u a b l e i n f o r m a t i o n t h a t they p r o v i d e . Other

Control

Methods

T h i s s e c t i o n of t h e book p r e s e n t s a v a r i e t y of s y n t h e t i c e x p e r i e n c e i n a wide a s s o r t m e n t of a g r o c h e m i c a l a p p l i c a t i o n s outside the standard areas. Included are s u c h a r e a s as s t r i g o l , p h e r o m o n e s , c h e m i c a l h y b r i d i z i n g a g e n t s , and p l a n t g r o w t h r e g u l a t o r s ( 4 0 ) .


a

1. BAKER ET AL.

Overview of Agrochemical Development 7

Conclusions The chapters of this book provide a look at the current synthesis rational employed in the agrochemical industry. We beleive this collection chronicles a significant proportion of the recent advances in the field. Only a very few compounds have those characteristics that encourage commercialization. The considerable body of knowledge reported here hopefully will aid those interested in the design of future active materials.


Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

16. 17. 18.

19.

Muller, P. Helv. Chim. Acta 1946, 29, 1560-80. Zimmerman, P. W.; Hitchcock, A. E. Contrib. Boyce Thompson Inst. 1942, 12, 321. Martin, H.; Shaw H. BIOS, Final Report 1946, No. 1095. Ware, G. W. Residue Reviews 1975, 59, 119-40. Benvenue, A. Residue Reviews 1976 , 61, 37-112. Beatty, R. G. The DDT Myth; John Day Co.: New York, 1973. Marco, G. J.; Hollingworth, R. M.; Durham, W., eds. Silent Spring Revisited; American Chemical Society: Washington, DC, 1986. Becker, W.; Langelueddeke, P.; Leditschke, H.; Nahm, H.; Schwerdtle, F. German Patent 2 223 864, 1973. Walworth, B. L.; Klingsberg, E. U. S. Patent 3 882 142, 1975. Jeffcoat, B.; Harries, W. N.; Thomas, D. B. Pesticide Sci. 1977, 8, 1-12. Kittleson, A. R. U. S. Patent 2 553 770, 1951. Kittleson, A. R. Science 1952, 115, 84-6. Delp, C. J.; Klopping, H. L. Plant D i s . Rep. 1968, 1 2 , 95. Ragsdale, N. N.; Kuhr, R. J., eds. Pesticides: Minimizing the Risks; ACS Symposium Series No. 336; American Chemical Society: Washington, DC, 1987. Magee, P. S.; Kohn, G. K.; Menn, J.J., eds. Pesticide Synthesis Through Rational Approaches; ACS Symposium Series No. 255; American Chemical Society: Washington, DC, 1984. Hansch, C.; Leo, A. Substituent Constants for Correlation Analysis in Chemistry and Biology; Wiley: New York, 1979. Olsen, E. C.; Christoffersen, R. E . ; eds. Computer Assisted Drug Design; ACS Symposium Series No. 112; American Chemical Society: Washington, DC, 1979. D'Amico, J. J. in Innovation and U. S. Research; Smith, W.N.; Arson, C. F . , ed.; ACS Symposium Series No. 129; American Chemical Society: Washington, DC, 1980, pp 143-6. Antoginini, J. J . Am. Sugar Beet Technologists, 1962, no. 2, 94-9.



8


20. T i l l e s , H. J . Am. Chem. Soc. 1959, 81, 714-27. 21. Crafts, A. S. in Advances in Pest Control Research, vol. 1, Metcalf, R. L., ed.; Interscience: New York, 1957, pp 39-80. 22. Crafts, A. S. The Chemistry and Mode of Action of Herbicides; Interscience: New York, 1961. 23. Corbett, J . R.; Wright, K.; B a i l l i e , A. C. The Biochemical Mode of Action of Pesticides, 2nd ed.; Academic Press: London, 1984. 24. Audus, L. J., ed. Physiology and Biochemistry of Herbicides; Academic Press: London, 1964. 25. Ashton, F. M.; Crafts, A. S. Mode of Action of Herbicides; Wiley: New York, 1973. 26. Kearney, P. C.; Kaugmann, D. D. Herbicides: Chemistry, Degradation and Mode of Action; 2nd edition, v o l . 1-2; Dekker: New York, 1975. 27. Moreland, D. E.; St.John, J . B.; Hess, F. D . , eds. Biochemical Responses Induced by Herbicides; ACS Symposium Series No. 181; American Chemical Society: Washington, DC, 1982. 28. Fletcher, W. W.; Kirkwood, R. C. Herbicides and Plant Growth Regulators; Granada: London, 1982. 29. Heitz, J . R.; Downum, K. R., eds. Light-Activated Pesticides; ACS Symposium Series No. 339; American Chemical Society: Washington, DC, 1987. 30. Hedin, P. A . , ed. Bioregulators for Pest Control; ACS Symposium Series No. 276; American Chemical Society: Washington, DC, 1985. 31. Britton, G . ; Goodwin, T. W., eds. Carotenoid Chemistry and Biochemistry; Pergamon: Oxford, 1982. 32. Cassida, J . E. Pyrethrum: The Natural Insecticide; Academic Press: New York, London, 1973. 33. Jacobsen, M.; Crosby, D. G. Naturally Occurring Insecticides; Marcel Dekker: New York, 1971. 34. E l l i o t t , M . , ed. Synthetic Pyrethroids; ACS Symposium Series No. 42; American Chemical Society; Washington, DC, 1977. 35. Coats, J . R., ed. Insecticide Mode of Action; Academic Press: New York, London, 1982. 36. Menn. J . J.; Beroza, M., eds. Insect Juvenile Hormones: Chemistry and Action; Academic Press: New York, 1972. 37. Green, M. B.; Spilker, D. A . , eds. Fungicide Chemistry: Advances and Practical Applications; ACS Symposium Series No. 304; American Chemical Society: Washington, DC, 1986. 38. Georghiou, G. P.; Saito, T . , eds. Pest Resistance to Pesticides; Plenum Press: New York, London, 1983. 39. Glass, E. H . ; et. a l . Pesticide Resistance: Strategies and Tactics for Management; National Academic Press: Washington, DC, 1986. 40. Mandava, N. B . , ed. Plant Growth Substances; ACS Symposium Series No. 111; American Chemical Society: Washington, DC, 1979. RECEIVED June 9, 1987 Baker et al.; Synthesis and Chemistry of Agrochemicals ACS Symposium Series; American Chemical Society: Washington, DC, 1987.

Overview of Agrochemical Development - ACS Publications

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