Table Of ContentC. Fest· K.-J. Schmidt The Chemistry of Organophosphorus Pesticides
C. Fest K.-J. Schmidt
The Chemistry of
Organophosphorus
Pesticides
Second Revised Edition
Springer-Verlag Berlin Heidelberg New York 1982
Dr. CHRISTA FEST
Dr. KARL-JULIUS SCHMIDTt
Bayer AG, Wissenschaftliches Laboratorium fOr Pflanzenschutz
0-5600 Wuppertal-Elberfeld
With 44 figures
ISBN -13 :978-3-642-68443-2 e-ISBN -13 :978-3-642-68441-8
DOl: 10.1007/978-3-642-68441-8
Library of Congress Cataloging in Publication Data
Fest, C. (Christa), The chemistry of organophosphorus pesticides.
Bibliography: p. Includes index.
1. Organophosphorus compounds. 2. Insecticides.
I. Schmidt, K.-J. (Karl-Julius), II. Title.
SB952.P5F47 1982632' . 95 82-813 AACR2
ISBN -13 :978-3-642-68443-2
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned,
specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying
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are made for other than private use, a fee is payable to Verwertungsgesellschaft Wort, Munich.
@ by Springer-Verlag Berlin Heidelberg 1973, 1982
Softcover reprint of the hardcover 2nd edition 1982
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a spe
cific statement, that such names are exempt from the relevant protective laws and regulations and therefore
free for general use.
215213140-543210
Dedicated to Dr. G. Schrader
Preface to the Second Edition
Rapid progress in the field of organophosphate compounds has made this new
edition necessary. Particular attention has been paid to new developments in
biologically active products as this is probably of greatest interest to practical
chemists. I have therefore updated the chapter on chemistry and, in connection
with this, rewritten the chapter on metabolism.
I should especially like to thank Professor Dr. HELLMUT HOFFMANN for his
constant encouragement and interest in my work and for many fruitful discus
sions.
The co-author to the 1st edition, Dr. KARL-JULIUS SCHMIDT, died suddenly on
November 21, 1980. I treasure the memory of a valued colleague of many years
standing.
Elberfeld, January 1982 CHRISTA FEST
VII
Preface to the First Edition
Our intention has been to provide a short introduction to the chemistry and
mode of action of insecticidal phosphoric acid compounds, with particular ref
erence to the relationship between structure and activity. The yearly produc
tion of these pesticides is now approaching 100,000 tons and thus offers an im
portant example of applied research. If, however, one examines the historical
development of these compounds, it is apparent that this was preceded by a
hundred years of pure chemistry of phosphorus. The utility of the phosphoric
acid pesticides is undisputed today - and furthermore it can be expected that
they will solve many of the world's nutritional problems, yet from this field of
applied research many paths are now leading back into basic research in chem
istry, biochemistry, biology and toxicology etc. This clearly illustrates the prob
lem of attempting to define pure and applied research.
Originally, this book was conceived for students of chemistry who, on comple
tion of their study, were uncertain about the place of applied research in indus
try but it was soon clear that such material, when supplemented with further
data, would serve as an introduction to the field of pesticidal phosphoric acid
compounds for many technicians, officials and scientists who, in various au
thorities in agriculture, in chemical and biological research, are concerned with
the problems of crop protection and more recently with questions of pollution
of the environment. We assume that anyone wishing to explore this whole field
more deeply will refer to specialized literature, for example, SCHRADER'S mono
graph or the Houben-Weyl handbook.
The existence of several names for the same product presents a special prob
lem. Industry is interested in using the registered name, while in scientific liter
ature the common name is preferred. We are of the opinion that anyone con
cerned with crop protection should have full command of both trade names
and common names. We have, therefore, made no special effort to distinguish
between either type of designation. We have, however, prepared two separate
tables collating these names. It is sufficient if, when using a name, one is aware
of its legal significance.
We are indebted to Professor R. WEGLER who prompted us to compile this
volume on Organophosphorus Pesticides. We are indebted also to many col
leagues for their co-operation and helpful criticism. We would like to thank Dr.
G. SCHRADER (Bayer AG) for his advice and encouragement, as well as Profes
sor G. UNTERSTENHOFER (Bayer AG) and particularly Mr. J. DIXON who has
translated this very difficult text into English. We are also grateful to Mr. J.
EDWARDS for the translation of the first pages of the chapter "Biochemistry",
and especially to Dr. H. MARTIN (London) for a final criticism and correction
of the manuscript.
Elberfeld, January 1973 The Authors
VIII
Table of Contents
1. Introduction . . . . . . . . . . . 1
1.1. Historical Development 12
2. General Section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20
2.1. Background .............................. 20
a) Electronic Structure, Types of Compounds .......... 20
b) Bond Properties ........................ 22
2.2. Reactivity ............ . 25
a) Hydrolysis, Alcoholysis . . . . 25
b) Alkylating Properties ..... 35
c) Phosphorylating Properties 38
2.3. Nomenclature .......... . 43
3. Chemical Section .............................. 50
3.1. Starting Materials . . . . . . . . . . . . . . . . . . . . . . . . . .. 50
a) Phosphorochlorido(thio)ates and Phosphonochlorido(thio)ates 52
b) Phosphoro and Phosphono(thioic) Acids . . . . . . . . . . .. 61
c) Di- and Trialkyl Phosphites and Phosphorothioites . . . . .. 66
3.2. Insecticides .............................. 80
a) Cyanidates and Fluoridates ................... 80
b) Anhydrides . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 83
c) O-Aryl Phosphor(n)o(thion)ates ........ 89
d) O-Aryl Phosphorothiolates and -dithioates . . . . 107
e) Heterocyclic Phosphor(n)o(thion)ates . . . . . . . 109
f) O-Phosphorylated Hydroxylamine Derivatives 122
g) S-Alkyl (subst.) Phosphoro(di)thioates ...... 123
h) Enolphosphates and -phosphorothioates .. . . . 149
i) Miscellaneous ....... . . . . . . . . . . 156
3.3. Other Compounds . . . . . . . . . . . . . . . . . . .. 158
a) Fungicides .............. . . . . . . . . .. 158
b) Herbicides .,. . . . . . . . . . . . .. 167
c) Chemosterilants . 177
4. Biochemistry 183
4.1. Mechanism of Action 183
a) Mechanism of Action in Mammals 183
b) Mechanism of Action in Arthropods ............. . 200
IX
4.2. Structure and Activity 206
4.3. Mixtures of Active Substances (Synergism, Antagonism) 217
4.4. Resistance . 221
4.5. Metabolism 243
a) Oxidation 246
b) Reduction 254
c) Isomerization 255
d) Hydrolysis . 257
e) Dealkylation and Dearylation 261
f) Degradation at the Carboxy Group 266
g) Conjugation .. 268
4.6. Toxic Action .... 272
4.7. Neurotoxic Action 282
5. Appendix 291
5.1. Trade Names and Common Names 293
5.2. Bibliography . . . . . . . . . . . . . 317
a) Chemistry of Phosphorus-Compounds 317
b) Insecticides (Activity, Biology, Metabolism) 317
c) Biochemistry and Enzyme Inhibition 318
d) Biochemistry of Insects 318
e) Statistical Analysis 318
5.3. References .. 319
5.4. Author Index 343
5.5. Subject Index 352
First Aid see page 282
x
1. Introduction
Crop protection by means of chemicals has become increasingly an object for
public discussion from about the time when RACHEL CARSON published her
book "Silent Spring". According to the understanding of the basic concepts in
volved in this difficult scientific field, two lines of argument follow which tend
to be ideological or of a more objective nature. One may regard chemical crop
protection simply as a profit-induced poisoning of the environment or one can
try to analyze the various factors that have compelled us to use chemical agents
in the production of food.
The deciding factor is the development of the world population to be expected
during the next decade (Fig. 1).
c 7
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4r--
3r--
21-
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0 I I I I I I I I
1000 1200 1400 1600 1800 2000
A.D.
Fig. 1. Numerical development of the world population in the period from 1000-2000 A. D.
Whether these figures are absolutely correct is of secondary importance, what
is quite certain is the expected development. The continuation of the curve
must remain open, for the growth of population will stabilize under the in
fluence of retarding factors. Otherwise the populated areas of Egypt would ac
cording to FUCKS [339] (see Table 1) possess a population density of more than
2000 people per square kilometer, which is equivalent to the density in the Eu
ropean capitals. Provision of food in the under-industrialized countries with a
high birth rate will become the most urgent problem of the next decades.
If curves such as that in Fig. 1 are expressed in kilocalories instead of number
of persons versus time and if a mean daily requirement per head of world pop-
Introduction
ulation is taken as 2420 cal, then, in 1970 9-10 thousand million kcal was pro
duced, in the year 2000 about 16 thousand million kcal will be produced and
by the year 2040 about 22 thousand million kcal. This does not, however, take
into consideration the protein content of food [339]. Food production must
therefore be doubled in the next three decades. This objective is technically
feasible if every agricultural possibility is exploited. CRAMER [234] cites the fol
lowing measures:
1) Expansion of cultivated areas
2) Improvement of soil cultivation
3) Mineral fertilization
4) Propagation of improved varieties
5) Improved irrigation
6) Improved agricultural structure
7) Modern crop protection.
In addition there will in future be the introduction of nonclassical techniques
which are independent of the soil, e.g. exploitation of the protein reserves of
the sea, hydroponic culture etc.
Table 1. Population density of various countries between 1950 and 2040 according to FUCKS
Country Inhabitants per square kilometer
1950 1963 1975 1995 2040
USA 19.9 20.2 25 30 35
Russia in Europe 27.0 30.4 35 40 45
Russia in Asia 2.6 3.0 3.5 4 4.5
USSR 8.6 10.0 11 13 15
China 56.45 74.9 100 160 270
Belgium 276.7 304.5 320 340 390
W.-Germany 189.5 223.5 240 260 290
United Kingdom 206.1 219.0 230 260 280
France 75.6 86.8 90 100 110
Italy 154.7 167.5 180 200 240
Netherlands 300.5 356.1 400 480 710
United Arab Republic 482.6 764 1050 1550 2350
Modern crop protection not only comprises the use of insecticides but also the
introduction of fungicides and herbicides which in mono-cultivation have con
siderable influence in determining the type and techniques of agriculture.
The second fact to be considered is that, since biblical times, the history of
agriculture has been a history of catastrophes. Here we follow CRAMER [234]
who to date has published the most comprehensive and careful estimate of
crop losses due to pests and pathogens. CRAMER cites numerous examples,
some of which have almost become classical, as for example the "turnip win
ter" of 1917 in Germany. Due to a severe attack of Phytophthora, practically the
entire potato crop was destroyed, so that" turnips became the basic source of
nutriment. This event demonstrates, as do many others, that such an occur
rence can have extensive political consequences.
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