Pestic. Sci. 1982, 13, 407-414

Insecticidal Activity of the Pyrethrins and Related Compounds. Part XII:. a-Substituted-3-Phenoxybenzyl Esters Michael Elliott, Andrew W. Farnham, Norman F. Janes and Bhupinder P. S . Khambay

Department of Insecticides and Fungicides, Rothamsted Experimental Station, Harpenden, Hertfordshire AL5 2JQ

(Revised manuscript received 14 September 1981)

Seventy-three a-substituted 3-phenoxybenzyl esters were synthesised, mostly using one of two general routes, based on the Grignard and related reactions. Esters with simpler (smaller and more polar) a-substituents were generally more insecticidally active; correlations based on substituent volume and substituent polarity parameters were about equally significant.

1. Introduction

One of the more striking advances in pyrethroid structure-activity relationships1 followed the introduction of an a-substituent, particularly cyano, into 3-phenoxybenzyl esters.2, As yet, few other a-substituents have been examined.4-7 A wide range of such esters (Figure 1) has now been synthesised and tested. The use of constant bioassay procedures allowed direct comparison and has led to a recognition, reported here, of the influence that some features of the a-substituent have on insecticidal activity.

2. Experimental>ethods 2.1. General Methods for the determination of mass spectra, and 1H and I3C nuclear magnetic resonance (n.m.r.) spectra, have been described previous1y.s Insecticidal activities against adult Musca domestica L. (houseflies) and Phaedon cochleariue Fab. (mustard beetles) were assessed by topical application of measured drops of solutions of the compounds in acetone as described el~ewhere.~

For substituent dimensions, measurements were taken directly from Stuart models (1 cm= 1 A) in the direction of the bond to C-a (L) and in the two directions orthogonal to it, Wi and Wz, giving the largest value to WI. Volume ( V ) is calculated as L x W1 x WZ. For substituent polarity, x constants were taken from a published set of data.lO

2.2. Alcohols made by Method A 3-Phenoxybenzaldehyde (10 mmol), in diethyl ether (10 ml) or tetrahydrofuran (10 ml), was added with stirring to a solution of the Grignard reagent at - 78°C prepared conventionally from alkyl halide (12 mmol) in diethyl ether (50 ml), or vinyl halide (12 mmol) in tetrahydrofuran (50 ml). Alkyl acetylenes were converted to their lithio derivatives using butyl-lithium, and treated similarly. After stirring for 1 h while the mixture warmed to 20°C, saturated ammonium chloride solution (50 ml) was added gradually. The organic layer, combined with a diethyl ether extract of the residue, was washed with 2~~hydrochloric acid and saturated sodium chloride, dried with anhydrous sodium sulphate and the solvent removed by evaporation. The resulting alcohol was examined

a Part XI: Pesric. Sci. 1978, 9, 112-116.

0031-613X/82/0800-0407 $02.00 0 1982 Society of Chemical Industry

407

408 M. Elliott et a/.

R I Figure 1. General structure of the esters synthesised

for the study. The acid moiety (R1) was either (1R)- trans chrysanthemic acid (Acid A), or (1R) cis-3-(2,2- dtbromovinyl) - 2,2 - dirnethylcyclopropanecarboxylic acid (Acid B). These esters of the alcohols I1 (Figure 2) with Acid A or Acid B are referred to as IIA and

uonCH-O-R'

\ \

(1) IIB, respectively.

spectroscopically and, when necessary, purified by distillation or preparative thin-layer chromato- graphy (t.1.c.) on silica, using appropriate mixtures of diethyl ether and hexane.

The alcohols made by Method A were as follows, and are given in the form: R in structure I1 (Figure 2), followed by the and the partial lH-n.m.r. spectrum from Ccr-H and from the a-

Method \ I

Figure 2. Methods of synthesis used to prepare the alcohols 11. The reagents employed are given in sections 2.2, 2.3 and 2.4 of the text.

substituent: CH3 (cf. reference 4), 1.5792; 4.4(q, 7 Hz), 1.4(d,3H); C2H.5, 1.5815, not determined; CH2==CH- (cf. reference 4), 1.5881, 5.3(m), 6.0(ddd, 1H), 5.0(m,2H); CH=C- (cf. reference 5),

2.2(t), I.5(m), l.O(t); CH3-(CH2)3-C-C -, 1.5689, 5.4, 2.2(t), 1.1-1.7(m), 0.9(m); Ph-C-C--, 1.6300, 5.7, under 6.9-7.7(m); CH2=CH-C-C--, 1.6010, ~ 5 . 8 , 5.5-6.l(m,3H); Ph-, 1.6180, 5.7,7.4(~,5H); 4-Cl-ceH4--, not determined; 3-CI--C&--, 1.6075, 5.6, under 6.7-7.6(m);p-tolyl, 1.6045, 5.6, 2.3(S,3H), under 6.8-7.6(m); m-tolyl, 1.5982, 5.6, 2.3(s,3H), under 6.8-7.6(m); 4-CH30-C6H4--, 1 S995, 5.6, 3.7(s,3H), under 6.6-7.5(m); 3-cH30-C&C-, 1.601 5, 5.7, 3.8(s,3H), under 6.6-7.6(m); Ph-CH2-, 1.5984, 4.7(t, 7 Hz), 2.9(d,2H), under 6.8-7.6(m).

1.6015, 5.3(d, 2 Hz), 2.5(d); CH3-C-C-, 1.5830, 5.4, 1.9; CH~-(CHZ)Z-C-C--, 1.5750, 5.4,

2.3. Alcohols made by Method B The acetylenic alcohol (5 mmol), in pyridine (50 ml) containing palladium on barium sulphate (lo%, 200 mg), was shaken in a hydrogenation apparatus until the hydrogen uptake decreased to less than 5 ml min-l, then filtered, diluted with diethyl ether and processed as described in Method A to give the corresponding cis-olefin. Alternatively, the acetylenic alcohols were reduced with 1.3 molar equivalents of aluminium lithium hydride in tetrahydrofuran by refluxing them together for 3 h. Addition of saturated ammonium chloride and processing as described in Method A gave the corresponding trans-olefin.

Insecticidal activity of a-substituted-3-phenoxybenzyl esters 409

The alcohols made by Method B were as follows (data as in section 2.2): cis-CHs-CH-CH--, 1.5796, 5.3-5.8(m,3H), 1.7(d,3H, 6 Hz); mm-CH3-CH=CH--, 1.5845, 5.6-5.9(m,2H), 5.l(d), 1.7(d,3H, 6 Hz); cis-Ph-CH=CH--, 1.5970, 25.6, 6.5 (d, 11 Hz), x5.8, under 6.8-7.6(m); trans-Ph-CH=CH--, 1.6270, 5.3(d, 7 Hz), 6.1-7.6(m).

2.4. Alcohols made by Method C The Grignard reagent from 3-bromophenyl phenyl ether11 (5 mmol) and magnesium ( 5 mmol) in diethyl ether (40 ml) was cooled to -78°C and treated gradually with a solution of the aldehyde (4.5 mmol) in diethyl ether (10 ml), followed by stirring for 1 h without cooling. Processing as described in section 2.2 gave the required alcohol.

The alcohols made by Method C were as follows (data as in section 2.2): tvans,trans-CHs-CH= CH-CH=CH--, not determined, 5. I-6.5(m,5H), 1.8(d,3H, 6 Hz); 4-CN-csH4-, 1.6041, 5.8, under 6.9-7.8(m); 3-CN-C&-, 1.6042,5.7, under 6.8-7.8(m); 3-PhO-C&-, 1.5450,5.9, under 6.8-7.7(m); CeF5, 1.5361, 6.2; 2-furyl, 1.591 1, 5.7, 6.l(m), 6.3(m), under 6.9-7.6(m); 3-fury1, 1.5869, 5.6, 6.3(s), under 6.8-7.7(m); 2-thieny1, 1.621 5 , 5.9, under 6.8-7.9(m); 2-pyridyl, m.p. 99-10O0C, 5.8, under 6.9-8.8(m); 3-pyridy1, 1.5688, 5.9, under 6.9-8.7(m); 4-pyridyl, m.p. 105-106"C, 5.8, under 6.9-7.6(m), 8.5(m,2H).

2.5. a-Fluoro-3-phenoxybenzyl bromide 3-Phenoxybenzaldehyde (20 g) was treated with hydrazine hydrate (10 g) in water to give an almost quantitative yield of the hydrazone, b.p. 152-152"/0.2 mmHg, of which 5.0 g was oxidised with silver oxide (5.67 g) and anhydrous magnesium sulphate (1.9 g) in diethyl ether (80 ml) at 20°C for 16 h (cf. reference 12). A portion (1 g) in diethyl ether (5 ml) of the reddish oil [a crude sample of (3-phenoxyphenyl)diazomethane], obtained by filtering and evaporating the solvent, was added to a solution of hydrogen fluoride-pyridine complex (70%, I0 ml) in dry diethyl ether (40 ml) at OT, and stirred for 30 min before pouring the product into ice water. The ether extract was washed with sodium hydrogen carbonate, dried with anhydrous sodium sulphate, and evaporated to a residue, which was purified by t.l.c., using diethyl ether+ hexane (1 + 9 by volume) as solvent, to yield 3-phenoxybenzyl fluoride (34% yield from the hydrazone); n.m.r. peaks at 5.3(d, 49 Hz) and 6.7-7.7(m). This fluoride (0.5 g) and N-bromosuccinimide (0.53 g) in refluxing carbon tetrachloride (20 ml) were treated with small portions of benzoyl peroxide over a period of 6 h, and then filtered and the solvent evaporated to yield a-fluoro-3-phenoxybenzyl bromide, m 2 0 1.5819, n.m.r. peak at 7.l(d, 49 Hz).

2.6. a-Acetyl-3-phenoxybenzyl alcohol A mixture of mercury(1I) sulphate (0.67 g), concentrated sulphuric acid (0.45 ml) and water (6 ml) was stirred at 20°C for 5 min; a portion of the product (0.2 ml) was diluted with methanol (0.4 ml), and a-ethynyl-3-phenoxybenzyl alcohol ( I .04 g) was added. After refluxing the mixture for 4 h, it was cooled and extracted with diethyl ether. After drying the extract with potassium carbon- ate, the solvent was removed and the residue (0.9 g) purified by t.l.c., using diethyl ether + hexane (1 $ 4 by volume) as solvent, to give the product (0.65 9); ~ ~ 2 0 1.5595, n.m.r. peaks at 5.0(s) and 2.l(s,3H).

2.7. a-(2-Bromovinyl)-3-phenoxybenzyl alcohol Di-isobutylaluminium hydride (1 M) in hexane (2 ml) was added to a-ethynyl-3-phenoxybenzyl alcohol (0.6 g) in hexane (5 ml) while cooling below 40°C; the product was then maintained at 50°C for 2 h. The solvent was removed under vacuum; the residue in dry tetrahydrofuran (10 ml) was then cooled to -50°C and treated with bromine (0.42 g) in tetrahydrofuian (2 ml). After warming to 20°C, the mixture was gradually acidified with 20% sulphuric acid; it was then poured on to ice-water and extracted with pentane (3 x 10 ml); the extract was washed with aqueous sodium hydrogen carbonate solution and processed as usual to isolate or-(2-bromovinyl)-3-phenoxybenzy1 alcohol (0.6 g).

410 M. Elliott ct a/.

2.8. a, a-Disubstituted-3-phenoxybenzyl alcohols Methyl 3-phenoxybenzoate (1.5 g) in diethyl ether (5 ml) was added dropwise at O'C, over a period of 15 min with vigorous stirring, to methylmagnesium iodide prepared from iodomethane (2.5 g) and magnesium (0.48 g) in diethyl ether (30 ml); stirring was continued for 4 h at 20°C. After the addition of saturated ammonium chloride solution and shaking with diethyl ether, the ether layer was separated, washed, dried and evaporated to give cc,cc-dimethyl-3-phenoxybenzyl alcohol (1.4 g); m.p. 53-54"C, n.m.r. peak at 1.6.

Table 1. Properties of the esters studied

R in structure I1

Number of unusual shifts in

13C-n.m r. spectrum

Ester LIA

CN- F- CH3- CZHS- CF3- CH3-CO- CHz=CH- Br<H=CH- cis-CH3-CH=CH- trans-CH3-CH=CH- cis-Ph-CH=CH- truns-Ph-CH=CH- truns,rrans-CH3-CH=CH-CH=CH- CHcC- CHs-CkC- CH~+CHZ)Z-GC- CH~-(CHZ)~-C=C- Ph-CkC- CHe=CH-C=C- Ph- 4-c1-C&4- 3 -CI-caH 4-

P-ToIYI- m-T~lyI- ~ - C H ~ O - C G H ~ - 3-CHsO-CeH4- 4-cN-CeH4- 3-cN-c~H4- 3-PhO-CeH4- c6FS- 2 - F ~ y l - 3 - F ~ ~ y l - 2-Thienyl 2-Pyridyl- 3-Pyridyl- 4-Pyridyl- Ph-CHa- CH3-, CHs CH-C-, CHGC- CHI-, CHSC-

Ref. 2 1 .5430 1 ,5420 1.5404 1.5072 1.5395 1.5500 1.5640 1.5506 1.5540 1.5605 1.5832 NM 1.5455 1.5518 1.5485 1.5435 1 S830 1.5615 1.5684 1.5700 1.5762 1.5695 1.5664 1.5668 1.5694 ss 1.5742 1.5730 ss 1.5572 1.5616 1.5773 1.5686 1.5628 NM ss NM NM 1.5498

6 4 0 0 5 3 1

10 0 0 0 0

2 0 0 0 0 0 0 0 0

0 0 0 2 2 0 4 0 0 0 3 3

0

-

-

-

- - 0

Ester IIB

Number of unusual shifts in

13C-n.m.r. spectrum

Ref. 3 1s 1.5792 1.5782 1.5502 1.5602 1 ,5674 NM 1.5817 1.5809 1.6025 1.6140 ss 1.5895 1.5857 1.5782 1.5750 1.6200 1.5868 1 ,6000 1.5908 1.6028 1.5920 1.5830 1.5884 1.5952 ss 1.5928 1.5880 ss 1.5830 1.5821 1.6100 1.5948 1.5780 1.5924 ss 1.5918 ss NM

6 4 0 0 4 2 0

0 0 0 0 1 1 0 0 0 1 2 0 0 0 0 0 0 0 2 3 0 3 0 0 0 0 1 2 0 7 4

-

-

NM =not made. SS = semi-solid. IS =insufficient sample.

Insecticidal activity of u-substituted-3-phenoxybenzyl esters 41 1

Similarly, addition of the same ester to excess ethynylmagnesium bromide in tetrahydrofuran gave a,a-diethynyl-3-phenoxybenzyl alcohol, which was purified by t.1.c.; n.m.r. peak at 2.6.

a-Ethynyl-3-phenoxybenzyl alcohol (0.7 g) in acetone (0.3 ml) was stirred at 0°C with a solution of chromium trioxide (0.2 g) in water (0.6 ml) and concentrated sulphuric acid (0.16 ml) for 1 h, to yield ethynyl 3-phenoxyphenyl ketone (0.66 g); nD2' 1.6039.

Addition of the ketone (0.5 g) to methylmagnesium iodide [prepared from iodomethane (0.32 g) in diethyl ether (10 ml)] gave a-ethynyl-a-methyl-3-phenoxybenzyl alcohol (0.5 g) ; n.m.r. peaks at 1.7(3H) and 2.5(1H).

2..9. Esters (1R)-trans-chrysanthemates and (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxyl- ates were made from the alcohols (11) by the reaction with the acid chloride as previously described,* or from the bromide by the reaction with the silver salt in refluxing carbon tetrachloride. These esters are hereafter referred to generally as IIA or IIB, respectively (see Figures 1 and 2). All the esters were checked for structure and purity by lH and 13C n.m.r. spectroscopy, and no significant impurity was detected. lH-Spectra were as expected from the constitutive acids and alcohols, and 13C chemical shifts were consistent with previously observed trends,13 including a number of unusual shifts which could be explained by through-space interaction between the a-substituent and the acid part of the molecule (cf. references 8 and 13). Shifts (in the acid part only) were counted as unusual if they fell outside the following ranges (numberings of carbons as in reference 13) in (IIA) esters: C-I, 171.0-172.1 ; C-2, 34.3-35.1 ; C-3, 28.5-29.3; C-4, 20.3-20.5; C-5, 22.0-22.2; C-6, 32.6-33.1; C-7, 120.7-121.2; C-8, 135.3-135.8; C-9, 25.425.5; C-10, 18.418.5 parts per million, and in (IIB) esters: C-1, 169.2-170.1; C-2, 31.4-32.1; C-3, 27.4-27.8; C-4, 14.9-15.2; C-5, 28.0-28.4; C-6, 35.5-35.8; C-7, 133.1-133.5; C-8, 89.3-90.7 parts per million. Table 1 shows the nDZo values and the number of unusual shifts in the 13C n.m.r. spectra for the esters.

3. Results and discussion

3.1. Synthesis Almost all previously synthesised a-substituted 3-phenoxybenzyl alcohols had been made from 3-phenoxybenzaldehyde (Figure 2). This route (see section 2.2) was directly applicable for several of the alcohols required for the present work. For instance, substituted alkynyl groups were intro- duced in good yield, and could be hydrogenated to the corresponding cis or trans olefins with appropriate reagents (section 2.3). Heterocyclic and some substituted aromatic groups for which the required aldehydes were readily available were more conveniently introduced by the inverse method (section 2.4).

Special routes were used to four of the alcohols. Alcohol I1 (R= CF3) was prepared by the pre- viously described route.6 Alcohols I1 (R = -CH=CHBr) and I1 (R= -COCH3)4 were made from the ethynyl compound I1 (R= -C-CH)5 with di-isobutylaluminium hydride followed by bromine (cf. reference 14), and with mercury (11) oxide and sulphuric acid (cf. reference 15), respectively. For the a-fluoro alcohol, a reported method16 for analogous compounds failed, but a subsequent modification7 gave the required compound (11, R=F). In the present work, a diazomethyl com- pound was treated with hydrogen fluoride/pyridine (cf. reference 17), followed by a-bromination and selective reaction of the more active halogen (bromine) with a silver salt (see section 2.5).

a,=-Disubstituted esters were made by the reaction of a Grignard or sodium derivative with ethynyl 3-phenoxyphenyl ketone (made by oxidation of the ethynyl alcohol), or with the 3- phenoxybenzoic ester.

The alcohols were esterified with two acids, known1 to give highly active pyrethroid esters, (1R)-trans-chrysanthemic acid (Acid A) and (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethy~cyclopro- panecarboxylic acid (Acid B).

41 2 M. EUiott et al.

Table 2. Relative toxicities of or-substituted-3-phenoxybenzyl esters to Musca domestica and Phaedon cochleariae

R in structure I1

H- (references 21-23) CN- (references 2,3) F- (reference 7) CH3- CZH5- CF3- (reference 6) CH3-CO- (reference 4) CHz=CH- (reference 4) lrans-Br-CH=CH-

I ~ ~ ~ S - C H ~ - - C H = C H -

trans-Ph-CH=CH- trans,trans-CHs-CH=CH-CH=CH- CHGC- (reference 4; cf. reference 5 )

c~s-CH~-CH=CH-

Ck-Ph-CH=CH-

CHa--C=C- CH~-(CHZ)Z-C=C- CH~-(CHZ)S-CGC- Ph-CSC- CHz=CH-C=C- Ph- 4-cl-ceH4- 3-Cl-ceH4- p-TO1yl- m-TOlyl- 4-MeO-C&b- 3-MeO-CeH4- 4-CN-CeH4-- 3-CN-CeH- 3-PhO-CeH4- C0F5 2 - F ~ y l - 3 - F ~ ~ y l - 2-Thienyl 2-Pyridyl- 3 -Pyridyl- 4-Pyridyl- Ph-CH2- CH3-, CHEC- CH3-, CH3- CHrC-, CHGC-

Relative toxicitya

Ester IIA Ester IIB

M. domestica P. tochleariae M. domesticn P. cochleariae

- ~ - ~ _ _ _ _ _ _ - ~ - ~ ~

-~ ~ ._ _ _ _ _ . ~ -

- . ~ ~ ~ - _ _ _ _ - - ~ ~~

90 50 180 360 150 90 630 1200

4.6 I5 90 0.8 11 9 50 35 2 0.9 I 1 8 3 3 29 24 1.3 1.3 5.4 10

30 20 80 130 3 5 0.2 1 5 10 4 7 40 23

<0.1 1 0 . 1 0 6 1 1 1 6 5

2 2 40 60 110 500 13 18 120 180

1 1 7 7 0 .4 0.4 3 2.2 2 z 2 6 8

16 7 7 70 0.2 0.6 2 4

<O.l <0.1 0 . 5 " 1 <0.1 <0 .1 1 . 6 2.5 < o . 1 2 0 . 3 2 3

0 .4 1 5 3 <O.l <0.1 1 2 <0 .1 1 0 . 1 1 1 < o . I <0 .1 10 1.5 <0.1 < o . 1 " 1 1 <0.1 < o . I 1 1 < O . l <0.1 < O . l <0 .1

0.8 2 1 1 10 -0.5 8 20 16 0.5 1.5 5 8

"0.1 "0.5 2 7 "0.5 1 2 4

- 1.5 3.6 <0.1 <0 .1 <0.1 < O . l - - <0.1 <0.1

- < o 1 <0 .1 1 0 . 1 < o . I

- -

- -

-

-

- -

a Relative to the standard, bioresmethrin= 100. Topical application tests to Musca dornestica L. and Phaedon cochleariae Fab.

3.2. Insecticidal activity The results of bioassays against houseflies and mustard beetles (Table 2) show the wide range of activities of the compounds examined. Esters of Acid B were consistently more active than those of Acid A. In the 25 instances where direct comparison was possible, the log of the factor by which the two esters differed (averaged for houseflies and mustard beetles) was calculated and a mean and standard error computed. The result, 0.86 (k 0.058), corresponds on average to a 7.3-fold increase in potency on changing from Acid A to Acid B.

Insecticidal activity of a-substituted-3-phenoxybenzyl esters 413

Table 3. Correlation coefficients for linear regressions of log(re1ative activity) against substituent polarity (n) or

substituent volume (V)

Esters Test species ‘n r v __--___ - -. -

IIA Musca dornestica 0.74 0.66 Phaedon cochleariae 0.75 0.72

IIB Musca domestica 0.76 0.66 Phaedon cochleariae 0.68 0.60

Preliminary examination of the results in Table 2 shows that increasing the complexity of the substituents led to corresponding reductions in the insecticidal activity. Attempts to correlate this trend with either substituent volume, or with substituent polarity were about equally successful ; separate linear regressions for logarithms of each of the four sets of relative activities in Table 2 against V (substituent volume) and n (substituent polarity), in turn, all gave similar correlation coefficients (see Table 3), explaining about half of the variance. However, V and T were themselves too strongly correlated to distinguish between them. Variation from the best-fit line was particularly large at the high activity end, so while small or highly polar a-substituents may induce high activity, other factors, that are as yet not properly understood, appear to be operating, and therefore pre- diction cannot be made with confidence. This is emphasised by recent results (to be published) in which the cyano group enhances the activity of esters of 3-substituted benzyl alcohols, but suppresses it in the corresponding 4-substituted compounds. Nonetheless, the study does indicate the area where active compounds are most likely to be discovered.

The results in Table 2 refer to esters of resolved acids with racemic alcohols, which are therefore mixtures of two diastereomers. Whenever the two components have been separately examined,l*-20 insecticidal activity was almost completely due to one of the two isomers, the other having been shown to be almost inactive. Esters with two a-substituents (Table 2, last three entries) were not significantly active, an important result which established that, even when the substituent is one known to be effective in the monosubstituted series, for instance ethynyl, the enhancement of the activity by one substituent is completely outweighed by the destructive effect of the other. This result reinforces the interpretation that even the cyano group, which enhances when in the (S)-a position and diminishes activity in the ( R ) series,ls can only augment effectiveness from a sterically non-disruptive region of the molecule, and that any substituent in the disruptive region removes activity almost totally.

Acknowledgements The authors are grateful to ICI (UK) Ltd, and Mitchell-Cotts Co. Ltd, for gifts of valuable inter- mediates, to the National Research Development Corporation for financial support, and to S. C. Jenkinson and K. E. O’Dell for technical assistance. Constructive comments from referees led to modifications, especially of section 3.2.

References 1. 2. 3.

4.

5. 6. 7. 8. 9.

Elliott, M.; Janes, N. F. Chem. Soc. Rev. 1978, 7, 473-505. Ger. Offen. 2 231 312 (1973) to Sumitomo Chemical Co. Ltd. Elliott, M.; Farnham, A. W.; Janes, N. F.; Needham, P. H.; Pulman, D. A. Nature (London) 1974, 248,

Matsuo, T.; Itaya, N.; Mizutani, T.; Ohno, N.; Fujimoto, K.; Okuno, Y.; Yoshioka, H. Agric. B i d . Chem. 1976, 40, 247-249. Belgian Patent 738 112 (1969) to BASF AG. Ger. Offen. 2 804 284 (1978) to FMC Corporation. European Patent 1944 (1978) to Roussel-Uclaf. Elliott, M.; Farnham, A. W.; Janes, N. F.; Johnson, D. M.; Pulman, D. A. Pestic. Sci. 1980, 11, 513-525. Elliott, M.; Farnham, A. W.; Ford, M. G.; Janes, N. F.; Needham, P. H. Pestic. Sci. 1972, 3, 25-28.

710-7 11.

414 M. Elliott et al.

10.

11.

12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23.

Hansch, C. ; Leo, A. J. Substituent Constants for Correlation Analysis in Chemistry and Biology Wiley-lnter- science, New York, 1979. Elliott, M.; Janes, N. F.; Pulrnan, D. A.; Gaughan, L. C.; Unai, T.; Casida, J. E. J. Agric. Food Chem. 1976, 24,270-276. Mohrbacher, R. J.; Crornwell, N. H. J. Am. Chem. SOC. 1957, 79,401-408. Janes, N. F. J . Chem. SOC. Perkin 1 Trans. 1977, 1878-1881. Zweifel, G.; Steele, R. B. J. Am. Chem. SOC. 1967, 89. 2754-2755. Hennison, G. F.; Watson, E. J. J. Org. Chem. 1958, 23, 656-658. Cainelli, G. ; Manescalchi, F. Synthesis 1976, 472473 . Olah, G. A.; Welch, J. Synthesis 1974, 896-898. Elliott, M.; Farnham, A. W.; Janes, N. F.; Soderlund, D. M. Pestic. Sci. 1978,9, 112-116. Matsuo, T.; Nishioka, T.; Hirano, M.; Suzuki, Y.; Itaya, N.; Yoshioka, H. Pestic. Sci. 1980, 11, 202-218. Elliott, M.; Janes, N. F.; Kharnbay, B. P. S. Pestic. Sci. 1980, 11, 219-223. Elliott, M. Bull. W.H.O. 1971, 44, 315-324. Ger. Offen. 1 926433 (1969) to Sumitorno Chemical Co. Ltd (Chem. Abstr. 1970, 72, 66647). Elliott, M.; Farnham, A. W.; Janes, N. F.; Needharn, P. H.; Pulrnan, D. A. Pestic. Sci. 1975, 6, 537-542.