Synthesis and Acaricidal Activity of Novel 2 ... - ACS Publications

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Downloaded by NORTH CAROLINA STATE UNIV on September 7, 2012 | http://pubs.acs.org Publication Date: November 23, 2004 | doi: 10.1021/bk-2005-0892.ch029

Synthesis and Acaricidal Activity of Novel 2-Substituted-3-trifluoromethylquinoxalines 1

1

1

1

Yoshitaka Fukushima, Naoki Ishii , Tetsuya Imai , Makio Usui , and Noriharu Ken Umetsu 2

1

Naruto Research Center, Otsuka Chemical Company, Ltd., Naruto, Tokushima 772-8601, Japan Otsuka Chemical Holdings Company, Ltd, Osaka 554-0021, Japan

2

Recently fluorine-containing compounds have attained importance as a target for useful agrochemicals. The 2substituted-3-trifluoromethylquinoxalines are a novel type of fluorine containing compounds designed and synthesized by our group, which exhibit excellent acaricidal and insecticidal activities. The reaction of o-phenylenediamine with ethyl trifluoropyruvate as afluorinesource, followed by chlorination leads to a common starting material for the aimed fluorine -containing chemicals. The reaction of the starting material with different types of nucleophiles such as amines gave a wide variety of 2-substituted-3-trifluoromethylquinoxalines. Some of the compounds synthesized showed excellent acaricidal activity against two-spotted spider mites (Tetranychus urticae), and some other compounds, in turn exhibited insecticidal activity.

Recentlyfluorine-containingcompounds have gained importance as a source for useful agrochemicals. Of them, trifluoromethyl (CF )-containing compounds were major target in obtaining new molecules, and a large number of compounds possessing C F moiety in the aryl ring were designed and commercialized as useful agrochemicals. On the other hand, limited number of CF -containing heterocyclic compounds have been so far designed and commercialized. 3

3

3

304

© 2005 American Chemical Society In New Discoveries in Agrochemicals; Clark, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.

305

ο (F^r^OEt Ο

Flufenacet (Herbcide)

Ο

_ /

Br Thifluzamide (Fungicide)

Ο

ο


N ^ N MeO^J^OMe "OEt

0

NyO

OEt

CF source 3

Chlrofenapyr (Insecticide)

Fluacrypyrim (Acaricide)

Design

Ethyl trifluoropyruvate Novel CF source 3

Heterocyctes Novel CF -contalnlng hetrocyclic compond

3-irifIuoromethylquinoxaline

3

Acarlcidal activity

Figure 1. Design of novel CF containinig heterocyclic compounds r

As shown in Figure 1, flufenacet (herbicide) possessing trifluoromethyl moiety in the thiadiazole ring, thifluzamide (fungicide) having trifluoromethyl moiety in the thiazole ring, fluacrypyrim (acaricide) possessing trifluoromethyl moiety in the pyrimidine ring, and chlorfenapyr (insecticide) having trifluoromethyl moiety in the pyrrole ring are a few examples for the C F containing heterocyclic agrochemicals (IS). These compounds are usually prepared from trifluoroacetate, trifluoroacetic anhydride or trifluoroacetoacetate as a trifluoromethyl source. In order to create novel class of agrochemicals, which contain CF moiety in the heterocyclic ring, we have designed and synthesized a series of 2-substituted-3-trifluoromethylquinoxalines (3-TFQ) by utilizing ethyl utilizing ethyl trifluoropyruvate. The pyruvate is considered to be a novel C F source for heterocyclic ring. The compounds thus synthesized possess unique structure in the molecule among various CF -containing heterocyclic compounds, and proved to be acaricidal active. 3

3

3

Synthesis The 2-substituted-3«TFQ were prepared according to the synthesis scheme shown in Figure 2. The first step is to react ethyl trifluoropyruvate I with a variety In New Discoveries in Agrochemicals; Clark, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.

r

306 of 0-phenylenediamines II in the presence of /?-toluenesulfonic acid monohydrate (p-TsOH) in toluene to obtain 3-TFQ-2-one III, which in turn was treated with phosphorus oxychloride to give 2-chloro-3-TFQ IV. The compound IV was then reacted with different types of nucleophiles such as amines in the presence of potassium carbonate in N, N-dimethylformamide (DMF) to give the aimed product 2-substituted-3-TFQ V.

V • 6-Cland7-Cl 3 3 26 6-F and 7-F 2 2 27 6~CF and 7-CF3 1 1 28 6-N0 and7-N0 1 1 6-PhCOand7-PhCO 29 Ό Activity index; 3: mortality 100%, 2: mortality 99-50%, 1 : mortality 49-0% Mixture of isomers


Compound

Λ

—

2

2

b)

b)

b

b)

b)

3

b )

2

a

b

2

2

Table IV. Effect of Substitution at R position of 6,7-Cl -3-TFQ on Acaricidal Activity (Comparison with Unsubstituted Compound on the benzene ring) 2

Activity (ppm)

0

Compd.

Activity (ppm)

3

R

R

Compd.

a

200 200 100 1 5 (CH ) CH 1 30 3 (CH ) CH (CH ) CH 31 3 1 6 (CH ) CH 3 (CH ) CH 32 3 3 7 1 (CH ) CH (CH ) CH (CH ) CH 33 3 8 2 3 (CH )aCH (CH ) CH 34 3 3 9 3 (CH ) CH (CH ) CH 22 3 3 10 3 (CHi)ioCH 35 3 2 11 (CH )toCH 3 (CH )„CH (CH ) CH 36 2 1 12 2 (CH ) CH 37 1 1 13 ( C H ) C H 1 Activity index; 3: mortality 100%, 2: mortality 99-50%, 1 : mortality 49-0% 2

4

3

2

4

3

2

5

3

2

5

3

2

6

3

2

6

3

2

7

3

2

7

3

9

3

2

8

3

2

2

9

3

2

3

a

3

3

2

2

U

3

2

2

12

3

2

3

3

12

3

In New Discoveries in Agrochemicals; Clark, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.

310 2

Table V. Effect of Substitution at R Position of 6,7-CI -3-TFQ on Insecticidal Activity 2

I 1

R

2


h

Insecticidal activity " Acaricidal activity " (ppm) (ppm) Compound R TSM" WFT" SLW 100 200 200 200 30 1 1 1 1 (CH ) CH 31 3 3 3 (CH ) CH 3 32 3 (CH ) CH 3 3 2 1 33 3 3 3 (CH ) CH 1 34 3 (CH ) CH 3 2 22 1 3 (CH ) CH 3 1 35 1 2 3 (CH2)ioCH3 1 36 1 1 3 (CH )„CH 1 37 3 1 (CH ) CH 1 1 Activity index; 3: mortality 100%, 2: mortality 99-50%, 1: mortality 49-0% WET: westernflowerthrips (F. occidentalis) SLW: silver leaf whitefly (B. argentifolii) TSM: two-spotted spider mite (F. urticae) 2

C

2

4

2

5

3

2

6

3

2

7

3

2

8

3

2

9

3

2

2

a

b

c

d

3

3

12

3

Data for the insecticidal and acaricidal activities for the substituted compound of R position with N, JV-dialkylaminoalkyl, alkoxyalkyl, alkoxycarbonylalkyl or acyloxyalkyl are shown in Table VI. As already mentioned, the compound 31 possessing w-hexyl group as R showed excellent acaricidal and insecticidal activities. Therefore, the compound having alkylamino, JV, JV-dialkylaminoalkyl, alkoxyalkyl, alkoxycarbonylalkyl or acyloxyalkyl as R , length of chain being similar to w-hexyl, were synthesized and their insecticidal and acaricidal activities were determined. As shown in the table, diethylaminopropylamino substituted compond, i.e., compound 38 showed excellent acaricidal activity at 20 ppm. Ethoxypropylamino substituted compound (41) also showed excellent insecticidal and acaricidal activities, activity level being equal to the w-hexylamino substituted compound 31. 2

2

2

Conclusion In order to create a novel class of acaricide and insecticide, a series of 2substituted-3-TFQ were synthesized by utilizing ethyl trifluoropyruvate as a novel source for C F moiety, and acaricidal and insecticidal activity were determined. 3


311

2

Table VI. Effect of R Position of 6,7-Cl -3-TFQ on Acaricidal and Insecticidal Activities


2

H

Insecticidal activity" (ppm)

Comod iompa.

31

/ ^ ^ ^ V \

38

. - " ^ ^ N ^

39

• - ^

40

a

b

c

d

κ

V

- ^ N ' '

^s^N,

41

. ^ ^ 0 " ^

42

, y ^ O ^

4 4

S^çyK

Acaricidal activity" (ppm)

C

WFT"

SLW

TSM*

200

200

200

WO

20

3

3

3

3

1

J

3

3

3

1

3

2

2

3

3

2

3

3

3

3

3

2

1

2

3

3

3

1

3

1

Activity index; 3: mortality 100%, 2: mortality 99-50%, 1 ; mortality 49-0% WET: westernflowerthrips (F. occidentalis) SLW: silver leaf whitefly (B. argentifolii) TSM: two-spotted spider mite (F. urticae)


312 Many of the compounds prepared showed excellent acaricidal activity against two-spotted spider mites (F. urticae), and some of them also showed good insecticidal activity against western flower thrips (F. occidentalis) and silver leaf whitefly (B. argentifolii). From the structure-activity relationship study, the CF group at 3-position of quinoxaline structure proved to be decisive for the acaricidal activity against two-spotted spider mites. The 6,7-Cl substitution on benzene ring of quinoxaline structure enhanced the acaricidal activity. The best acaricidal activity of substituted quinoxaline at 2-position was found with diethylaminopropylamino group. When the 2-position of quinoxaline was substituted with w-hexyl group or ethoxypropylamino group, these compounds showed excellent insecticidal activity for both insects tested as well as acaricidal activity. 3


2

References 1. 2. 3. 4. 5.

Deege, R. BCPC-Weeds, 1991, 87. Bloomberg, J. R. Abst. WSSA, 1995, 5. O'Reilly, P. Brighton Crop Pro. Conf.-Pests and Diseases, 1992, 427. Kirstgen, R; Oberdorf, K; Schütz, F; Theobald, H; Harries, V . WO 9616047, 1996. Addor, R. W.; Babcock, T. J.; Black, B. C.; Brown, D. G.; Diehl, R. E.; Furch, J. Α.; Kameswarm, V.; Kamhi, V. M.; Kremer, Κ. Α.; Kuhn, D. G.; Lovell, J. B.; Lowen, G. T.; Wright, D. P.: "Synthesis and Chemistry of Agrochemicals III", American Chemical Society, 1992, pp 281.


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