Synthesis and Chemistry of Agrochemicals

479 Pages·1987·5.65 MB·English

by  Don R. Baker

Synthesis and Chemistry
of Agrochemical

ACS SYMPOSIUM SERIES 355
Synthesis and Chemistry
of Agrochemicals
Don R. Baker, EDITOR
ICI Americas Inc.
Joseph G. Fenyes, EDITOR
Buckman Laboratories, Inc.
William K. Moberg, EDITOR
E. I. du Pont de Nemours & Co.
Barrington Cross, EDITOR
American Cyanamid Company
American Chemical Society, Washington, DC 1987

Foreword
The ACS SYMPOSIU
medium for publishing symposia quickly in book form. The
format of the Series parallels that of the continuing ADVANCES
IN CHEMISTRY SERIES except that, in order to save time, the
papers are not typeset but are reproduced as they are submitted
by the authors in camera-ready form. Papers are reviewed under
the supervision of the Editors with the assistance of the Series
Advisory Board and are selected to maintain the integrity of the
symposia; however, verbatim reproductions of previously pub
lished papers are not accepted. Both reviews and reports of
research are acceptable, because symposia may embrace both
types of presentation.
Preface
^REVOLUTIONARY CHANGES have linked chemistry with agriculture during
this century. Agricultural chemicals, properly chosen and applied, offer
great benefit to food and fiber producers and consumers alike. The need for
new agrochemicals has not abated. Indeed, the growing demand for safe
and effective agricultural chemicals has spurred major research effort for
new products. The prime goal of researchers is discovering materials that
will economically control plant pathogens insect pests and weeds and at
the same time be of minima
general.
The challenge for scientists who seek to discover and develop new crop
protection chemicals has escalated dramatically. It is becoming increasingly
more difficult to satisfy the many safety requirements of the various
regulatory agencies. The costs associated with development of a new
agrochemical are escalating. Until recently, the challenge has been
compounded by the lack of regular scientific interchange among those
chemists involved in the discovery process. With the ever-increasing world
population, the assistance that these new compounds bring to food
production is critical. We hope that the work reported here will be useful
to those who accept this challenge.
We have organized a series of symposia at each national meeting of the
American Chemical Society, beginning with the St. Louis meeting in 1984.
The aim of these symposia has been to provide a forum for presenting the
synthesis and chemistry of new agrochemical agents. In addition, chemists
have seized their opportunity to discuss the biological properties of the new
materials. These symposia are providing a focus for agricultural chemists.
In a similar vein, we hope that this book will provide a view of the
current synthetic effort in the agrochemical field. In this volume, a variety
of topics has been assembled, ranging from that first symposium to the
recent one held in Anaheim in 1986. The chapters in this collection show
varied approaches to the discovery process in the agrochemical field, and
they represent the current status of these synthetic efforts. The information
has been updated to convey the current state of the endeavor.
In the past, publication of new synthetic chemistry and the structures
of novel agrochemicals has been largely in the patent literature because
most of the major advances come from the agrochemical industry. Many
xi
interesting discoveries have not been made accessible because the
compounds lacked commercial potential. The agrochemical synthesis
symposia have provided at least a parallel avenue for synthesis chemists to
make their discoveries public. Furthermore, these symposia provide a
unique forum for this assemblage of pesticide chemistry.
Because most of the synthetic effort in the U.S. agrochemical industry
is devoted to the development of new herbicides and insecticides, much of
the information found in this book is devoted to these two major fields. An
effort was also made to give representation to the other important areas of
agrochemical synthesis. We particularly appreciate the efforts of those who
provided these extraordinary chapters.
We express appreciation to the authors for sharing this large amount
of useful chemistry and, most importantly, for sharing their practical insight
into the workings of biologically active molecules. We thank the companies
and organizations that hav
hope that by providing a
available for agrochemical discovery and by sharing viewpoints of many
scientists, this volume can contribute to continuing the successful partner
ship of chemistry and agriculture.
DON R. BAKER
ICI Americas Inc.
Richmond, CA 94804
JOSEPH G. FENYES
Buckman Laboratories, Inc.
Memphis, TN 38108
WILLIAM K. MOBERG
Agricultural Products Department
E. I. du Pont de Nemours & Co.
Wilmington, DE 19898
BARRINGTON CROSS
Agricultural Research Division
American Cyanamid Company
Princeton, NJ 08540
June 9, 1987
xii
Chapter 1
Overview of Agrochemical Development
Don R. Baker 1, Joseph G. Fenyes 2, William K. Moberg3, and
Barrington Cross4
1ICI Americas Inc., 1200 South 47th Street, Richmond, CA 94804
2Buckman Laboratories, 1256 North McLean Boulevard, Memphis,
TN 38108
3Agricultural Products Department, E. I. du Pont de Nemours & Co.,
Experimental Station, Building 402, Wilmington, DE 19898
4Agricultural Research Division American Cyanamid Company P.O Box
400
Since the earliest of recorded time, man has fought with
the environment in tilling his fields. At first 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 first 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
first generation of organic agrochemicals. The farmer's
yields were greater and costs were lower. But the first
generation compounds did not solve all 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 environ
mental concerns, DDT became embroiled in controversy (6-
7). 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
2 SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS
foxtails (Setaria sp.) became problems in the United
States. In Europe the problem weeds were the cleavers
(Galium sp .) , chickweed (Ste11 aria sp,), blackgrass
(Alopecurus myosuroides), and wild oats. Wild oats
became such a problem in Europe that control of this
single weed was incentive enough to develop herbicides
solely for i t s control. Compounds such as diclofop-
methyl (ji ) , difenzoquat (90 » and flamprop (10.) were
developed to meet this need.
The metallic fungicides used in the first half of the
twentieth century were largely replaced by the protective
fungicides such as captan (11-12) and later the new
systemics such as benomyl (13).
Gradually the unwanted side effects of these first
generation agrochemicals made i t apparent that a
successful agrochemical t hav th environ
mental, toxicological
addition to i t s basi
general requirements has several criteria that must be
satisfied before a particular compound is commercialized
(]A_) . Tens of thousands of compounds must be prepared and
tested before one is found that has a suitable combination
of properties that will warrant commercial development.
Since the cost of generating any new product is stagger
ing, only products targeted toward markets which have a
high potential for profit are developed. A negative side
effect of this process is that chemicals for minor crop
markets are often ignored. Therefore, any process that can
lessen the number of compounds prepared and tested before
a commercial product is found is of major importance.
The question is often asked, "How do you discover a new
agrochemical?" The random synthesis and screening method
gave us the first generation of agrochemicals. As we have
seen, however, these compounds were not without their
problems. The next successful approach is exemplified by
the organophosphate insecticides. Here the dimethyl or
diethyl dithiophosphate group was attached to just about
any type of available building block. This approach was
later extended to include the phosphonate analogs.
Through a comparison of the insecticidal and toxicological
data, structure-activity theories were developed which
provided a means for the synthesis of safer compounds. A
similar approach was used in the 2,4-D area. A l l manner
of substituted phenoxy and benzoic acids and their
derivatives were prepared. As a result, much was learned
about the structural relationships for the auxin type
action. This analog synthesis procedure has often been
called "me too chemistry". The patent literature abounds
with examples of such a strategy tried on almost every
thing that has shown a modicum of biological activity.
Just as 2,4-D i s a mimic of natural auxin, most critical
natural products peculiarly associated with plants,
insects or microorganisms have been studiea with a wide
variety of mimics, and analogs. Now i t is a common