Chapter 18
Amidrazones: A New Class of Coleopteran Insecticides
Downloaded by PENNSYLVANIA STATE UNIV on June 18, 2012 | http://pubs.acs.org Publication Date: May 14, 1998 | doi: 10.1021/bk-1998-0686.ch018
J.A.Furch,D.G.Kuhn, DavidA.Hunt,M.Asselin,S.P.Baffic, R. E. Diehl, Y.L.Palmer, andS.H.Trotto Cyanamid Agricultural Research Center, American Cyanamid Corporation, P.O. Box 400, Princeton,NJ08543-0400
The goal of modern crop protection is becoming increasingly focused on finding agents that control specific agricultural pests while leaving non-target organisms unaffected. At Cyanamid's Agricultural Research Center in Princeton, NJ our search for such agrochemicals has recently uncovered a novel class of amidrazone-based insecticides. More importantly, these novel insecticidally-active compounds appear to target specifically certain coleopteran insects, and in particular the southern corn rootworm Diabrotica undecimpunctata while being relatively non toxic to lepidoptera and other insects as well as to acarina, fish, and birds. These compounds also exhibit low toxicity towards mice. A structure-activity profile of these compounds was developed and the details of this work are discussed.
At Princeton our biologists screen a large variety of chemical compounds against a diverse number of insect orders and acarina in order to uncover new agrochemical leads. In that screen the amidrazone 1 (Figure 1) was found to be highly toxic towards the southern com rootworm Diabrotica undecimpunctata with an L C value of 0.06 ppm, which is equivalent to current commercially applied compounds such as Counter™ (Compound 2, Figure 1).
2
ι 0.06 ppm
Counter® 0.05 ppm
Figure 1 Southern Com Rootworm L C {Diabrotica undecimpunctata) 50
178
©1998 American Chemical Society
In Synthesis and Chemistry of Agrochemicals V; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1998.
50
179 More importantly however was that no toxicity was noted when this compound was administered to other insects (i.e. lepidoptera) or acarina. While the amidrazone class of chemistry is well known (7), until our discovery their insecticidal properties were not. Because of this potential opportunity to control specifically an important agricultural pest, an analog program was initiated to define further the biological activity of this novel group of compounds. Synthesis
Downloaded by PENNSYLVANIA STATE UNIV on June 18, 2012 | http://pubs.acs.org Publication Date: May 14, 1998 | doi: 10.1021/bk-1998-0686.ch018
Owing to their ease of synthesis as well as the large variety and availability of starting materials, an extensive library of amidrazones was conveniently and rapidly prepared by the route shown in Figure 2.
Figure 2. General Synthesis of Amidrazones The procedure involved reacting a substituted phenylhydrazine 3 with an acyl halide plus base under S chotten-Bauman conditions to generate the hydrazide 4 in greater than 95% yield. Compound 4 was then treated with 2 or more equivalents of thionyl chloride in toluene under reflux for several hours, then the solvent was removed under vacuum to yield the hydrazonyl halide 5 which was used generally without further purification. The reaction of 5 with either two or more equivalents of a nucleophilic amine or one equivalent of such amine plus one or more equivalents of triethylamine in a solvent such as diethyl ether quantitatively yielded the amidrazone 6. Biological activity We quickly discovered that even minor changes to the amidrazone molecule had profound effects on southern com rootworm ( SCR) LC data. 50
Effect of Phenyl substitution. Biological activity was especially sensitive to the presence and position of certain functional groups on the phenyl ring. The general trends observed was that compounds containing electron withdrawing groups in the ortho and para positions of the phenyl ring were more active while meta substituents as well as electron-donating groups were less active or inactive. Table I is a summary of the biological data and it is evident that the most active
In Synthesis and Chemistry of Agrochemicals V; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1998.
180 compounds always contained a CF group in the para position of the phenyl ring with either 2,6 dichloro or 2-chloro-6-nitro in the remaining positions (1, 7). 3
Table I. Effects of Phenyl Substitution on SCR L C ^ Data W
H H N ^
Downloaded by PENNSYLVANIA STATE UNIV on June 18, 2012 | http://pubs.acs.org Publication Date: May 14, 1998 | doi: 10.1021/bk-1998-0686.ch018
Y W
X
10
CI CI Br CI CI
CF CF CF CF CF
11
CI
12
Compound Number
Y
Ζ Cl N0 Br H H
Cl
H H H H N0 H
CI
H
13
H
CF
14
H
CF
15
H H
H
CF
16
H
H
17
Cl
H
CF
1 7 8 9
3 3
3
3
3
2
SCR LC25
CH C H C H C H CH CH=CH
0.50 0.06 0.46 7 0.04
2
8
SCR LC
