Ann. appl. Biol. (I972), 70, 233-243

Printed in &eat Britain 23 3

Investigations on fungicides : XIV. Fungitoxicity of N-(2,2,2 -trichloro -1 -methoxyethyl) -

formamide and related compounds

BY G . A. CARTER, L. A. SUMMERS" AND R. L. WAIN Agricultural Research Council, Plant Growth Substance and

Systemic Fungicide Unit, Wye College ( University of London), Ashford, Kent

(Accepted 18 February 1972)

SUMMARY

From a study of forty compounds related to the systemic fungicide N,N'-bis(~-formamido-z,~,~-trichloroethyl)-piper~ine, known as triforine (CELA W524), it was found that a new compound, N-(z,z,z-trichloro-I- methoxyethy1)-formamide, controls Erysiphegraminis on wheat when applied to the roots in sand. A number of N-(z,z,2-trichloro-1-aryloxyethyl)-form- amides and alkyl N-(2,2,z-trichloro-1-arylaminoethyl)-carbamates protect broad beans against Uromyces fabae and wheat against Erysiphe graminis ; some of these formamides show slight activity when applied to plant roots.

I N T R O D U C T I O N

A number of synthetic organic compounds have recently been discovered which possess systemic fungicidal activity against plant pathogens and some are now used commercially. Many earlier compounds, known to be systemic, were of a low level of activity and generally disappointing in field conditions (Summers, 1968). The types of molecule now known to possess fungicidal properties provide an opportunity to study chemical structurelactivity relationships in order to attempt to rationalize systemic fungitoxicity in terms of chemical properties.

Among the more important of recent discoveries are the oxathiins, carboxin (I; X = S) and oxycarboxin (I; X = SO,) (von Schmeling & Kulka, 1966) which are effective chemotherapeutants for many smut and rust diseases. Study of structure/ activity relationships (Edgington, Walton & Miller, 1966 ; Edgington & Barron, 1967; Snel, von Schmeling & Edgington, 1970; Hardison, 1971 a) revealed that some varia- tions of the oxathiin and phenyl moieties did not substantially diminish the in vitro fungitoxicity and the chemotherapeutic activity. The amide or peptide linkage, -NH . CO-, however, appears to be essential (von Schmeling & Kulka, 1966). This was confirmed, for example, by the discovery of systemic fungicidal properties in the pyran (I; X = CH,) (Tank & Grossmann, 1971). The benzimidazoles, thiabendazole (Staron & Allard, 1964; Staron et al. 1966; Weinke, Lauber, Greenwald & Preiser, 1969), furidazole and benomyl (Catling, 1969), have attracted considerable interest as

* On sabbatical leave from University of Newcastle 2308, New South Wales, Australia.

234 G. A. CARTER, L. A. SUMMERS AND R. L. WAIN

I

CCI3.CH .NH.COR I

N H I

IV

CCl3.CH.NH.CHO I R

I

CCI3.CH.NH.COOEt

V

CCI,. CH. NH . COR I

CCI,. CH .NH .COR

111

CCI,. CH.NH. CHO I P

VI

CC1,. CH . NH. CO. R I

O R

VIII

R I CClp. CH. NH . CHO

VII

systemic fungicides. Structure/activity relationships in these compounds have been investigated (Gilpatrick, 1969; Solel, 1970; Fuchs, Homans & de Vries, 1970; Edgington, Khew & Barron, 1971) and evidence has been obtained that benomyl(I1; R = CO.NH.Bu) readily breaks down in aqueous solution to the stable, equally toxic methyl benzimidazol-z-yl carbamate (I1 ; R = H) which probably is the actual toxicant (Clemons & Sisler, 1969; Peterson & Edgington, 1970; Maxwell & Brody, 1971). It is of interest that another systemic fungicide methyl thiophanate is readily transformed into (11; R = H) in aqueous solution and it would appear that the activity of both methyl thiophanate and benomyl is due to this breakdown product (Selling, Vonk & Sijpesteijn, 1970; Vonk & Sijpesteijn, 1971).

Work on systemic fungicides shows many to be active against powdery mildews. Such molecules often contain a nitrogen heterocycle to which is attached a lipid soluble grouping. For example, the pyrimidine dimethirimol (Elias, Shephard, Snell & Stubbs, 1968; Geoghegan, 1969) is effective against powdery mildew of cucumber while its analogue ethirimol controls powdery mildew on cereals (Bebbington, Brooks,

Studies on fungicides. X I V 235 Geoghegan & Snell, 1969). In this category too are the morpholines, cyclomorph (Kradel & Pommer, 1967) and tridemorph (Kradel, Pommer & Effland, 1969a,b; Pommer, Otto & Kradel, 1969; Pommer & Kradel, 1967) and another pyrimidine, triarimol (Arnold, Lade & Christensen, 1971 ; Gramlich, Schwer & Brown, 1969; Brown & Hall, 1971). A selective systemic fungicide for wheat rust, 4-n-butyl-1,2,4- triazole, also falls within this chemical type (von Meyer, Greenfield & Seidel, 1970).

Triforine, N,N'-bis-( 1-formamido-2,z,2-trichloroethyl)-piperazine (CELA W524) (111; R = R' = H) is also effective systemically against powdery mildews and other diseases (Schicke & Veen, 1969; Fuchs, Doma & Voros, 1971), and it is interesting to note that another chloral derivative, I ,I ,1-trichloro-~-nitro-2-propanol, first examined as a fungicide by Bates, Spencer & Wain (1963) shows systemic activity against smut fungi (Hardison, 1971 b) . Moreover, triforine is closely related to the mildew fungicide N-[~,~,~-trichloro-~-(~,~-dichloroanilino)ethyl]-formamide (IV; R = H, R' = 3x1, R' = 4-Cl) for which the common name chloraniformethan has been suggested (Vogeler, 1969). We have studied the effect on biological activity of certain modifications in the molecules of triforine (compound no. 39) and chloraniformethan (compound no. 40). These modifications include replacement of the formamido group -NHCHO, by carbamate -NH . COOR, a moiety present in benomyl and its breakdown product, and replacement of the piperazine ring system with other groupings.

MATERIALS

The chemicals are listed in Table I. Known compounds had melting points in agreement with literature values. The synthesis of new compounds is described by Summers (1972).

METHODS

The methods used for assessing inhibition of spore germination, evaluating protectant and eradicant activity and measuring activity in a leaf disk test are des- cribed by Lehtonen, Summers & Carter (1972) and only a brief outline of these tests will be given here.

Spore germination test The test chemicals were dissolved (or suspended) in acetone and measured volumes

pipetted into the depressions of microscope cavity slides. The solvent was evaporated and a standard volume of a suspension of spores of a test fungus added to each dry deposit. Germination andgerm tubegrowth were assessed after 16 h incubation at 25 "C.

Tests for protectant and eradicant activity Pre-germinated wheat seedlings (cv. Eclipse) were potted into compost and grown

until the first leaf was 10-12 cm long but still erect. Seeds of broad bean (cv. Sutton's Giant Windsor) were germinated in sand, potted into compost and grown until the lowest two pairs of leaflets were fully expanded.

Chemicals were applied formulated in 50% aqueous acetone, 10 ml of each treat- ment being sprayed on duplicate pots each containing one broad bean or five wheat seedlings. Protectant sprays were applied immediately prior to inoculation; eradicant

Com- pound no. I 2 3 4 5 6 7 8 9

I 0 I1 I2 I3 I4 I5 16 I7 I8 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39

40

236

Formula R IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV V V VI VI VI VI VI VI VI VI VI VI I11 I11 VII VII VIII VIII VIII VIII VIII I11

IV

OMe OMe OMe O M e O M e OMe OMe OMe OEt OEt OEt OEt OEt OEt OEt OEt OEt CHs 0 H 2-c1 3x1 4-c1 3-c1 2x1 2-Me 3-Me 4-Me 3-Me OMe OEt 0 NH H OEt

G. A. CARTER, L. A. SUMMERS AND R. L. WAIN

Table I . Chemicals related to triforine and chloraniformethan

R R Name H 2x1 3-Cl 4-c1 2-Me 3-Me 4-Me 3-Cl H 2-c1 3-Cl 4-Cl 2-Me 3-Me 4-Me 3x1 2-c1

H Methyl N-(z,z,z-trichloro-I-anilineothy1)-carbamate H Methyl N-[z,z,z-trichloro-~-(~-chloroanilino)ethyl]-carbamate H Methyl N-[~,~,~-tri~hlor~-~-(~-chloroanilino)ethyl]-carbamate H Methyl N-[z,z,~-trichloro-~-(~-chloroanilino)ethyl]-carbamate H Methyl N-[z,z,z-trichloro- I-(2-methylanilino)ethyl]-carbamate H Methyl N-[z,~,~-tri~hlor~-~-(~-methylanilino)ethyl]-carbamate H Methyl N-[z,z,z-trichloro-~-(~-methylanilino)ethyl]-carbamate 4-Cl Methyl N-[z,z,~-trichloro-~-(~,~-dichloroanilino)ethyl]-carbamate H Ethyl N-(z,z,z-trichloro-I-anilinoethy1)-carbamate H Ethyl N-[z,z,z-trichloro- 1-(2-~hloroanilino)ethyl]-carbamate H Ethyl N-[z,~,~-tri~hlor~-~-(~-chlor~anilin~)ethyl]-carbamate H Ethyl N-[z,z,n-trichloro-~-(~-chloroanilino)ethyl]-carbamate H Ethyl N-[z,z,z-trichloro-~-(~-methylanilino)ethyl]-carbamate H Ethyl N-[z,z,z-trichloro-~-(~-methylanilino)ethyl]-carbamate H Ethyl N-[z,z,z-trichloro-~-(~-methylanilino)ethylJ-carbamate 4x1 Ethyl N-[z,z,z-trichloro-~-(~,~-dichloroanilino)ethyl]-carbamate 4x1 Ethyl N-[z,z,z-trichloro-~-(z,~-dichloroanilino)ethyl]-carbamate

Ethyl N-(z,2,~-tri~hlor0-1-piperidin0ethyl)-carbamate - - - - H - H - H - H - 4x1 - 4-Cl - H - H - H - 5-Me - OMe - OEt - 0 NH - H - H - H -

-

NHZ N(Me)z H - H Me - H H -

Ethyl N-(z~z~z-trichloro-~-m~rpholinoethyl)-carbamate N-(z,z,z-trichloro-~ -phenoxyethyl)-formamide N-[z,z,z-trichloro-I -(z-chlorophenoxy)ethyl]-formamide N-[z,z,z-trichloro- I -(3-chlorophenoxy)ethyl]-formamide N-[z,z,z-trichloro-~-(~-chlorophenoxy)ethyl]-formamide N-[~,z,z-trichloro-~-(~,~-dichlorophenoxy)ethyl]-formamide N-[z,z,z-trichloro- I -(z,4-dichlorophenoxy)ethyl]-formamide N-[z,z,z-trichloro-~-(~-methylphenoxy)ethyl]-formamide N-[z,z,z-trichloro- I -(3-methylphenoxy)ethyl]-formamide N-[2,2,z-trichloro- I -(4-methylphenoxy)ethyl]-formamide N-[z,z,z-tri~hlor~-~-(~,~-dimethylphenoxy)ethyl]-formamide N,N'-bis( I -carbomethoxyamino-z,z,z-trichloroethyl)-piperazine N,N'-bis( ~-carboethoxyamino-z,z,~-trichloroethyl)-piper~ine 0.0'-bis( I-formamido-z,z,z-trichloroethy1)-hydroquinone N,N'-bis( I -formamido-~,~,~-trichloroethyl)-p-phenylenediamine N-(z,z,z-trichloro-I-hydroxyethy1)-formamide Ethyl N-(2,2,2-trichlor0-1-hydr0xyethyl)-carbamate N-(z,~,~-trichloro-~-hydroxyethyl)-urea N-(z,z,z-trichloro- I -hydroxyethyl)-N'N'-dimethylurea N-(z,z,z-trichloro-I-methoxyethy1)-formamide N,N'-bis( I -formamido-z,z,z-trichloroethy1)-piperazine, CELA WGZA (triforine)

I . , H 3-Cl 4-Cl N-[z,z,z-trichloro-~-(~,~-dichloroanilino)ethyl]-formamide

(chloroaniformethan)

sprays against wheat mildew were applied when the developing infection was just visible to the naked eye.

Wheat seedlings were inoculated with dry conidia of Erysiphe graminis tritici shaken from infected piants. Broad bean seedlings were sprayed with a suspension of uredo- spores of Uromyces fabae followed by incubation under high humidity for 48 h. For both wheat and bean, disease development on each treated leaf was assessed on an arbitrary scale of 0-5.

M.p. ("C)

129 131

1.52

I03 I35 I77 88 107 76 I34 109 80

141 119 73

107 115

73

93 I 06 85 74 95 82 118 190 dec. 185 dec. 215 17odec.

107 15odec. 155 dec. 140

I 80 dec.

131

163

I22

I02

I20

I20

Studies on fungicides. XIV 237

Leaf disk test Disks of cucumber leaf tissue inoculated with either conidia of Sphaerotheca

fuliginea or a drop of a suspension of conidia of Colletotrichum lagenarium and disks of broad bean leaf tissue inoculated with dry uredospores of Uromyces fabae were floated, inoculated side uppermost, on solutions or suspensions of the test compounds at 500, 100, 20 and 4 ppm. The development of disease symptoms on each disk was assessed on an arbitrary scale of 0-5.

Root application test This test for systemic activity was performed as follows: seed of wheat (cv. Eclipse)

was germinated on moist filter paper at 22.5 "C in dim red light for 3 days until the coleoptiles were 2-3 cm high. Uniform seedlings were potted into plastic cups of approximately 80 cc capacity, five seedlings per pot, containing either air-dried sand or soil (EFF potting compost). 20 ml of a test solution was then applied as a drench. Sand-grown plants also received 2 ml of a concentrated mineral nutrient solution (Standard Solufeed : Plant Protection Ltd.).

The seedlings received a further 20 ml of test solution on the seventh day and were inoculated on the ninth day by shaking wheat plants heavily infected with Erysiphe graminis over them.

Mildew development was assessed on the first leaf of each seedling on an arbitrary scale of 0-5 based on the percentage leaf area infected. Phytotoxicity was assessed both at the time of inoculation and at disease assessment.

RESULTS

Activity in spore germination tests Compounds 1-40 were all tested for fungistatic activity in spore germination tests

against Alternaria brassicicola, Botrytis cinerea, Septoria nodorum and Uromyces fabae. Those compounds which completely inhibited spore germination of at least one test fungus below IOO ppm or which inhibited germ tube growth by 50% at concentrations below 50 ppm are listed in Table 2.

Protectant and eradicant activity All compounds were tested as protective fungicides against both U. fabae on broad

bean and E. graminis on wheat at IOO ppm. Apart from triforine (no. 39) only those which gave less than 25 % of control infection are given in Table 3. These same com- pounds were also tested as eradicants against E. graminis (Table 3).

Activity in leaf disk tests All compounds were included in this test against powdery mildew, Sphaerotheca

fuliginea and anthracnose, Collectotrichum lagenarium on cucumber, and the rust U. fabae on broad bean. Only the compounds in Table 4 showed significant activity.

238

Compound no.

I 0 I1 I 2 I3 I 4 15 18

23 24 25 26 27 28

29 40

22

G. A. CARTER, L. A. SUMMERS AND R. L. WAIN

Table 2. Spore germination tests" Conc. (ppm) required to inhibit germination

by 1ooy0 - Conc. (ppm) required to inhibit germ tube growth by 50 yo

* > A.b. U.f. A.b. B.c. S.n. U.f.

- - - - - - - I 0

25-50 10-25

25-50 25-50 25

10-25 5-10

-

2.5-5 5-10

2'5-5 25 25

I 0-2 5 25

10-25 10-25 10-25 25-50 25

25-50 25-50 25 5-10

* Results are only presented when compound at 100 ppm completely inhibited spore germination

A.b. = Alternaria brassicicola. S.n. = Septoria nodorum. B.c. = Botrytis cinerea. U.f. = Uromyces or inhibited germ tube length by 50 % at 50 ppm.

fabae. Table 3 . Protectant and eradicant activity of chemicals

related to triforine and chloraniformethan Protectant activity"

Compound no.

I

5 6 9

I 4 I5 22 23 24 25 26 27 28

29 39 40

Oxycarboxin Karathanet

I1

U.f. (100 PPm)

C D C A A A A B B C D D D D B D B A -

E.g. ( P P d

I00

A A A A A A A A A A A A A A A C A

A -

20

B C B A A A A C C A C D D C D D A

A -

4

D D D C C D D D D D D D D D D D A

A -

Eradicant activity" E.g.

( P P d - C D C D B C C D B D C D D D A D B D A D A D C D D D D D A D C D A A

A A

I 0 0 20

- -

* Infection grades as % of control on scale A = < 25 %, B = 25 - 50 %, C = 50-75 %, D = 75-

t Mixed ~,4-dinitro-6-0ctylphenyl crotonates and 4,6-dinitro-z-octylphenyl crotonates. i7.f. = Uromyces fabae. E.g. = Erysiphe graminis.

I00 %.

Tabl

e 4.

Act

ivity

of c

hem

icals

rela

ted

to tr

iforin

e an

d ch

lora

nifo

rmet

han

in le

af d

isk a

nd r

oot a

pplic

atio

n te

sts

Lea

f di

sk t

est

Roo

t app

licat

ion,

A

I

1

whe

at+

f ,

Bea

n*

, \

Com

- S

.f. (

PP

4

c.2. (P

Pd

U

.f. (

PP

4

Soil

Sand

po

und

, ,

I

>r

Cuc

umbe

r*

Ex

. (pp

m)

A

,

I

no.

500

IOO

20

4

500

IOO

20

4

500

IOO

20

4

50

0 IOO

500

IOO

2'3

5 --

5 5

--

5 5

-- I0

0

I00

roo+

IOO+

14

I00

I00

68

++

8

4+

+

20

0.6

5 5

--

1.7

4.7

- -

5 --

26

o+

+

3.6

- -

5+

+

5 - -

4'7+

5

- - l

oo++

I00

+++

76

++

40

++

loo+

28

2'5+

5 - -

38

0

45

5 -

41

5

5-

4

42

5 -

+++

84

f ++

+ o

+

39

0

0.5

0.9

3.2

42

s

55

0

1'4

4'3

5 O

+

32

o+

0

40

+++

of

+ 0

.1 0

.4

+++

5+

+

5 5

4+

42+

5 5

92

88

76+

+ 6

8

5 5

--

5+

5 -- 96

94

* D

isea

se g

rade

d on

sca

le 0

-5.

Tox

icit

y ex

pres

sed

on s

cale

+ to

+ +

+ (p

lant

kill

ed).

t In

fect

ion

grad

es a

sses

sed

as p

erce

ntag

es o

f co

ntro

l. T

oxic

ity

asse

ssed

+ to

+ + i-

(pla

nt k

illed

). S.

f. =

Sph

aero

thec

a ful

igin

ea.

C.1

. = C

olle

totr

ichu

m la

gena

rium

. U.f

. = U

rom

yces

faba

e. E

.g. =

Ery

siph

e gr

amin

is.

N

w

\o

240 G. A. CARTER, L. A. SUMMERS AND R. L. WAIN

Activity in root application tests Compounds effective against cucumber mildew in leaf disk tests were examined by

root application in soil and sand against wheat mildew. Although inactive in the leaf disk tests, the bis derivatives (nos. 30, 31) were also included in the root application tests because of their close relationship to the systemic fungicide N,N'-bis( I -forma- mido-2,2,z-trichloroethyl)-piperazine (no. 39) : They were ineffective. The most active compounds (nos. 38 and 39) were re-tested at lower concentrations by root application against wheat mildew (Table 5).

Table 5. Systemic activity" of N-(2,2,2-trichloro-1 -methoxyethyl)-formamide (compound no. 38) and N,N'-bis( I-formamido-z,z,z-trichloroethy1)-piperazine (compound no. 39) against Erysiphe graminis of wheat when applied to soil and sand

Soil (ppm) Sand ( P P 4 I r >-

Compoundno. 500 250 125 62.5 zoo 100 50 25

o + + t o+ 18+ 70 o+ o+ 15+ 59 o * o o o - - - _ 38

39

* Infection grades expressed as percentage of control. 1. Toxicity at time of disease assessment expressed on a scale + -+ + + + . The toxicity of compound 38 showed as a yellowing and spotting of the apical portion of the first leaf

and sometimes of the second leaf also.

D I S C U S S I O N

The spore germination tests show that, as a group, compounds 1-40 are not highly active in inhibiting spore germination or germ tube growth of the test organisms A. brassicicola, B. cinerea, S . nodorum and U. fabae. The ethyl N-(z,z,z-trichloro- I-arylaminoethy1)-carbamates (nos. 9-17) are more fungistatic than the methyl analogues (nos. 1-8). Synthesis of higher alkyl esters will be undertaken to verify if this trend is maintained. The N-(z,z,z-trichloro-I-aryloxyethy1)-formamides (nos. 20-29) are among the more active fungistats, but compound 40, chloraniformethan, is the most effective substance examined in the in vitro tests. It is noteworthy that triforine (no. 39) and related bis derivatives (nos. 30-33) are poor fungistats against our test organisms although against other fungi, for example, Aspergillus niger and Clado- sporium cucumerinum, triforine has been found to have distinct fungitoxic activity (Fuchs et al. 1971).

In the protectant tests against bean rust and wheat mildew (Table 3) similar results were obtained. Good activity is confined to the alkyl N-(2,2,2-trichloro-1 -arylamino- ethyl)-carbamates (nos. I , 5,6,9,11,14,15) and the N-(2,2,z-trichloro-1-aryloxyethyl)- formamides (nos. 22-29) although none of these compounds was as active as chlorani- formethan (no. 40), which was also the most effective eradicant. In these tests triforine (no. 39) was a poor protectant at ~ o o p p m , the highest concentration examined, although the results of Schicke & Veen (1969) indicate that greater concentrations effectively control E. graminis on rye and Puccinia recondita on wheat. Lower rates are effective against barley and cucumber mildews (Fuchs et al. 1971). None of the bis derivatives (nos. 30-33) or the compounds 34-38 were found here to be useful pro- tectants at IOO ppm (Table 3).

Studies on fimgicides. XIV 241 The leaf disk and root application tests revealed some interesting results (Table 4).

With the exception of compound 14, which is a carbamate and which was only slightly active, all the compounds (nos. 20, 26, 28, 38, 39, 40) which showed activity are derivatives of formamide. Furthermore, small changes in chemical structure greatly affect activity in these tests. In the bis series (nos. 30, 31, 32, 33, 39) changing the formamido group to carbamate or altering the piperazine ring to a related diamine (no. 33) or hydroquinone (no. 32) completely removes activity. Likewise, with the aryloxyformamides (nos. 20-29) only the unsubstituted and two of the methyl substituted compounds are active (nos. 20, 26, 28). Moreover, by replacement of the methoxy group of compound 38 by hydroxyl (no. 34) systemic activity disappears.

The results also indicate little correlation between in vitro or protectant activity and activity when applied to plant roots. Triforine (no. 39) is a poor protectant at IOO ppm against U. fubae on broad bean and E. gruminis on wheat and is a poor fungistat, but it is active in the leaf disk test against cucumber mildew and is very effective against wheat mildew on root application. Schicke & Veen (1969) also found it to be very active when applied through roots against rye powdery mildew and wheat leaf rust. On the other hand, compound 40, the best protectant, although showing high activity in the leaf disk test against S. fuligineu, was not very effective when applied through roots against wheat mildew, possibly because of poor translocation. Likewise, compound 38 has little activity as a fungistat and protectant yet it controls wheat mildew by root application to sand although phytotoxic. Its low activity in soil is presumably due to adsorption. Most of the other compounds in Table 4 also showed little activity when applied to the soil.

The marked systemic activity of the new compound 38 and of CELA W524 (compound 39) is shown by the results of a second test on wheat plants growing in soil and sand (Table 5 ) . Both molecules possess the chemical grouping CCl, . CH . NH . - CHO and this may well be the important active moiety. Related alkoxy and alkylthio derivatives are being investigated.

REFERENCES

ARNOLD, W. R., LADE, D. H. & CHRISTENSEN, C. D. (1971). Efficacy of triarimol (EL-273) against Venturia inaequalis and Podosphaera leucotricha. Phytopathology 61, 884.

BATES, A. N., SPENCER, D. M. & WAIN, R. L. (1963). Investigations on fungicides. VII. The antifungal activity of certain hydroxy nitro alkanes and related compounds. Ann. appl. Biol, 51, 153.

BEBBINGTON, R. M., BROOKS, D. H., GEOGHEGAN, M. J. & SNELL, B. K. (1969). Ethirimol: A new systemic fungicide for the control of cereal powdery mildews. Chkky Ind. p. 1512.

BROWN, I. F. & HALL, H. R. (1971). Studies on the activity of triarimol (EL-273) against certain powdery mildew fungi. Phytopathology 61, 886.

CATLING, W. S. (1969). Benomyl - a broad spectrum fungicide. Proc. 5th British Insecticides and Fungicides Conf. Brighton, p. 298.

CLEMONS, G. P. & SISLER, H. D. (1969). Formation of a fungitoxic derivative from Benlate. Phytopathology 59, 705.

EDGINGTON, L. V. & BARRON, G. L. (1967). Fungitoxic spectrum of oxathiin compounds. Phyto- pathology 57, 1256.

EDGINGTON, L. V., KHEW, K. L. & BARRON, G. L. (1971). Fungitoxic spectrum of benzimid- azole compounds. Phytopathology 61, 42.

EDGINGTON, L. V., WALTON, G. S. & MILLER, P. M. (1966). Fungicide selective for Basidio- mycetes. Science, N.Y. 153, 307.

16-2

242 G. A. CARTER, L. A. SUMMERS AND R. L. WAIN ELIAS, R. S., SHEPHARD, M. C., SNELL, B. K. & STUBBS, J. (1968). 5-n-Butyl-2-dimethyl- amino-4-hydroxy-6-methylpyrimidine: a systemic fungicide. Nature, Lond. 219, I 160.

FUCHS, A,, DOMA, S. & V~ROS, J. (1971). Laboratory and greenhouse evaluation of a new systemic fungicide, N,N'-bis-( I-formamido-z,a,z-trichloroethy1)-piperazine (CELA W524). Neth. J. Pl. Path. 77, 42.

FUCHS, A., HOMANS, A. L. & VRIES, F. W. de (1970). Systemic activity of Benomyl against Fusarium wilt of pea and tomato plants. Phytopath. Z . 69, 330.

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