Insecticides-Pyramidines

2. PYRIMIDINES
Presented by:
Ch. Naga Satyasri
BAM-14-28

3. • Pyrimidine is an aromatic heterocyclic
organic compound.
• Six-membered heterocyclic ring with
two nitrogen atoms at positions 1 and 3.
• All pyrimidine fungicides active against
powdery mildew fungi.
• Chemical structure:

4. • Six pyrimidine fungicides have been
developed. These are fall in to two distinct
groups.
• First group:
Triarimol
Fenarimol
Nuarimol
• Second group:
Ethirimol
Dimethirimol
Buperimate

5. Triarimol
• The code number EL-273 by Eli Lilly &Co. Of
the U.S.A.
• α-(2,4-dichlorophenyl)-α-phenyl-5-pyrimidine
methanol

6. • It was a broad spectrum fungicide being
highly effective against apple and pear scab,
powdery mildew of furits, cereals and roses
and yellow rust of wheat.
• In the initial stages it showed very promising
results, but in late 1972 the development of
this fungicide was suspended due to
undesirable toxicological effects on the
laboratory test animals. Since the
compound is not being developed.

7. Fenarimol
α-(2-chlorophenyl)-
α-(4-chlorophenyl)-
5-pyrimidinemethanol
C17H12Cl2N2O
Nuarimol
C17H12Cl FN2O
α-(2-chlorophenyl)-
α-(4-fluorophenyl)-
5-pyrimidinemethanol.

8. Fenarimol Nuarimol
Trade name Rubigon, Bloc Trimidal
Code number EL-222 EL-228 by Eli Lilly& Co.
Molecular weight 331.2 314.7
Colour White crysatlline solid White crysatlline solid
Melting point 117o to 119 oC 1240c to 1250c
Solubility soluble in most organic
solvents. In water it is
13.7ppm soluble at 25 oC and
pH7.
It is soluble in most organic
solvents. In warer it is 26ppm
soluble at 250c and pH 7.
Acute oral LD50 2500 mg/kg 1250mg/kg
Formulations 50% W.P., 1 lb/gal E.C and 1
lb/gal aqueous suspension
0.75 lb/gal E.C., 1 lb/gal
aqueous suspension, and 5
percent solution seed coating,
formulations

9. Fenarimol
• Diseases controlled:
• It is evaluated against powdery
mildew of grapes, powdery mildew,
scab and rust of apple, dollar spot,
large brown patch, fusarium blight,
and snow mould of turf and powdery
mildew of roses.

10. • Mode of Action:
• It is a broad spectrum fungicide.
• In vitro some genera in Ascomycetes,
Basidiomycetes and in Deuteromycetes are highly
sensitive.
• In sensitive fungi the spore germination is not
inhibited but germ tube elongation is restricted.
• Germ tubes are thickened and malformed.
• It shows volatile and acropetal systemic action. In
seedlings through leaf application (spot or band
treatment) or through seed treatment it gets
accumulated in leaf tips.

11. • It is supposed to act through inhibition of the
ergosterol biosynthesis in the sensitive fungi.
• As seed treatment at 2g/kg seed it was
phytotoxic to wheat but lower rates ineffective
against stripe rust (Puccinia striiformis) disease.
• Application of fenarimol 12.5 E in late season
(mid-April) on pear trees at 30ml/100 l
concentration at 10 litres per tree rate
significantly reduced the ascospore production by
Venturia pirina.

12. • When these fungicides used as curative
treatment under poor conditions (like low
temperature about 5oC) for absorption a
number of applications are required to
maintain suppression of latent lesions. It is
effective against powdery mildew and apple
scab.

13. • Resistant strians:
• In Aspergillus nidulans mutants resistance to
fenarimol was related to reduced uptake of
the fungicide, the resistant mutants have
reduced fitness due to increased excretion of
fungal metabolites.
• Pencillium italicum strain resistant to
fenarimol was cross resistant to bitertanol,
etaconazole, fenapanil and imazalil but had
negatively correlated cross-resistance to
fenpropimorph.

14. • Accumulation of fenarimol by several fungi is
assumed to be the result of non-mediated
diffusion into mycelium (influx) and active
transport from mycelium (efflux).
• The force of fenarimol efflux may be the
proton motive force over the cell membranes
generated by membrane ATPase.

15. Nuarimol
• Mode of Action:
• It provides protectant, curative and eradicant
activity against certain diseases.
• Trimidal is being evaluated for control of
disease of trees, vines, peanuts and
vegetables, and as a seed treatment for
cereals.

16. • In vitro nuarimol effectively inhibits the
growth of cochliobolus sativus.
• As seed treatment it controls barley seedling
infection from seed to airborne Cochliobolus
sativus inoculum.
• In case of spring wheat seed treatment (1 to
1.5 a.i./kg) resulted in shorter subcrown
internodes, more coleoptiles-node
tillers/(CNT) and more CNTs producing fertile
tillers and resulting in reduced intensity and
common root rot and slight yield increase.

18. • At 10μM it strongly inhibits in vitro growth of
take-all of wheat (Gaeumannomyces graminis
var.tritici).
• A 2.2 kg per hectare soil drench in autumn
suppressed the disease but yield increase was
not there. May be it is phytotoxic at that rate.

19. • Ethirimol, Dimethirimol and Buperimate
belong to other group of pyrimidine
fungicides.
• Both ethirimol and dimethirimol are
hydroxyamino pyrimidines with alkyl
substitutions in the nucleus.
• Both these compounds were developed by
Imperial Chemical Industries. Ltd., U.K.
• In these derivatives the presence of an oxygen
function (carbonyl or hydroxyl) at the 4-
position, and the 2-alkylamino group are
essential for their systemic fungicidal activity

20. Dimethirimol
5-butyl-2-(dimethylamino)-6-methyl-4(1H)-pyrimidinone
C11H19N3O

21. • It is developed under the code number PP-675.
• Molecular weight 209.28.
• Hydrochloride form has molecular weight of
245.7
• It is a white crystalline solid with no odour and is
stable to heat and in alkaline and acid solutions.
• At 25oc it has a solubility of 0.12 percent in
water, 6.5 percent in ethanol, 4.5 percent in
acetone, 120 percent in chloroform, and 36
percent in xylene.
• It is also soluble in aqueous solutions of strong
acids.

22. • It is not corrosive to metals.
• The liquid formulations available are highly
acidic (pH 2.0) and hence corrosive.
• It is available commercially as Milcurb as JF-
2405 a 1.25 percent, JF-2305 a 10 percent, or
JF-2587 a 12.5 percent liquid formulations as
aqueous solution of hydrochloride salt.
• It has an acute oral LD50 for rats of more than
4000mg/kg.

23. • Dimethirimol is active against Sphaerotheca
fuliginea on cucumber, melons, marrows and
squahes.
• It is also effective against Erysiphe
cichoracearum , Podosphaera leucotricha and
Sphaerotheca pannosa.
• It is not active against powdery mildew of vine
(Uncinula necator) and most other
phytopathogenic fungi.

24. • Uptake and Translocation:
• It is uptake by roots, moves through xylem tissues
to stems and leaves, and finally gets accumulated
at the margins of leaves.
• It is loosely bound on to moist soils, so that soil
acts as a source for continous absortption of the
chemical by the plant roots.
• As foliar spray it shows only limited movement.
On application to a leaf it moves across the leaf
towards the tip and from upper to the lower
surface but not to petiole or up to new growth. In
woody species it shows poor systemicity due to
limited translocation.

25. • Degradation:
• The persistence of deposits of dimethirimol in
or on leaf is relatively short.
• Its half-life in plants under certain conditions
is only three to four days.
• It is rapidly metabolised in the leaves of young
or fruit bearing cucumber plants.
• Loss of one N-methyl group occurs very quicky
forming a N-desmethyl derivatives, (5-n-butyl-
4-hydroxy-6-methyl-2-methylamino-
pyrimidine) which is a very active fungicide.

26. • The second N-methyl group is lost slowly,
finally giving a non-fungitoxic amino
compound, (2-amino-5-n-butyl-4-hydroxy-6-
methyl pyrimidine).
• In cucumber fruits the fungicide is
metabolised at a slower rate.

27. • Phytotoxicity:
• Normally it is not phytotoxic but an overdose
may become injurious.
• Lower doses may also cause phytotoxicty if
roots are confined to a pot or surface layer of
soil, liquid application has been made in very
dry soils, or roots are absorbing the fungicide
from nutrient solution.
• A well established cucumber plant could
tolerate up to 1 g a.i./plant while young
plants may be degraded by this rate.

28. • Development of Resistant strains:
• In Holland it was used on large scale in 1969 for
cucumber powdery mildew control under
greenhouse conditions.
• Within one year, reports of failure of fungicide due
to the development of tolerant strains of the
fungus (Sphaerotheca fuliginea) were made.
• Since then several cases of development of
resistant strains of the pathogen have been
reported in glasshouse crops in north-western
Europe.

29. • Dosage:
• It is recommended for application to the soil
• 3 to 10 litres of Milcurb per hectare for
cucumbers and 10 to 15 litres per hectare for
squashes.
• For foliar spray 500ml Milcurb in 250 liters water
per hectare is recommended.
• For cucumber in greenhouse the
recommendation is 20ml/plant at the base of the
stem according to the age of the plant.

30. • Mode of Action:
• Dimethirol is fungicidal within the host plant
leaves at concentration below 10-7 M and is
consequently believed to be non-competitive
enzyme inhibitor.
• The activity of ethirimol and dimethirimol is
antagonised by the presence of folicacid and
riboflavin and is reduced by adenine, thiamine
and uracil.
• Riboflavin due to photochemical reaction with
dimethirimol antagonises its toxicity.

31. • Experiments with powdery mildew spores
suggest that these fungicides inhibit purine
biosynthesis, the metabolism of orotic acid
and glycine, and possibly interfere with
several pyridoxal-dependent enzymes.

32. Ethirimol
5-n-butyl-2-(ethylamino)-6-methyl-4(1H)-pyridimidinone
C11H19N3O

33. • Developed under the code number PP-149.
• Molecular weight: 209.3
• It is a white crystalline solid, stable to heat in
acid and alkaline solutions .It is almost
insoluble in water and acetone, very slightly
soluble in diacetone, alcohol and ethanol,
soluble in chloroform, trichloroethylene and
aqueous solutions of strong acids and bases.

34. • It is non-corrosive to metals, but the
hydrochloride salt formulation is corrosive to
galvanised containers.
• It is available under the trade name ‘Milstem’
as 8 percent D.P. for spray or as a seed dressing,
46.7 percent ‘Col’ (aqueous suspension) for
seed dressing or spray, a 20 percent aqueous
solution (acidic) and as granular formulations.
• The 80 percent D.P. formulation was stable for
six months at 370c.
• It has an acute oral LD50 for rats of 4000mg/kg
body weight.

35. • It is particularly effective against powdery
mildew (Erysiphe gramins hordei) of barley
controlling all mildew races on all varieties of
barley.
• It is also effective against powdery mildew of
wheat, oats, various grasses, and of some
dicots also. It has no activity against cereal
rusts.
• Ethirimol protected wheat and raya seedlings
for three weeks against powdery mildew.

36. • Seed treatment or granule application in soil
at 3 kg and 1kg per hectare gave complete
control of powdery mildew of cereals, in
protected plants vigour and root weight
increased.
• Uptake and Translocation:
• From soil or through seed treatment the
chemical is taken up by plant roots and is
translocated via transpiration stream to all
parts of the plant and can eradicate the
established infection as well as provide
prolonged protection.

37. • In spring barley ethirimol seed treatment
increased infection of Rhynchosporium secalis
significantly and reduced yields.
• When seed treatment with ethirimol
restricted the mycorrhizal development of
Endogone spp.

38. • Resistant strains:
• Erysiphe graminis strains resistant to ethirimol
have been reported.
• By continuous maintenance of Erysiphe graminis.
f.sp. hordei for 17 generations on barley plants
treated with sublethal dose the fungus adapted
to moderate concentrations of ethirimol but
tolerance was less stable. From treated barley
fields also less ethirimol sensitive E.graminis
isolates were obtained. The resistance in field
isolates of E.graminis hordei to ethirimol is
controlled by a complex heritable system and not
by one major gene.

39. • Degradation:
• It is fairly stable in soil.
• In barley and wheat plants it is rapidly (half
life of three days) metabolised by N-
dealkylation giving rise to a non-fungitoxic
amino compound. Water soluble metabolites
are also formed.
• Mild hydrolysis of the water soluble
metabolite fraction from ethirimol gives back
ethirimol, ethirimol glucoside, des-ethyl
ethirimol and a minor product in which
hydroxylation of the butyl group has occurred.

40. • Mode of Action:
• It inhibits appressoria formation during
primary infection of the Erysiphe graminis
f.sp.hordei, but other stages of mildew
development are also affected.
• Adenine and adenosine reduced ethirimol
fungitoxicity.
• Ethirimol inhibits RNA synthesis, it may
interfere with adenine metabolism at some
site subsequent to its synthesis.

41. Bupirimate
5-butyl-2-ethylamino-6-methylpyrimidin-4-yl-dimethylsulfamate
C13H24N4O3S

42. • Molecular weight: 316.4
• It is a pale tan waxy solid melting at 500 to 510 c.
• In water it is 22g per litre soluble.
• It is soluble in most organic solvents except
paraffin hydrocarbons.
• Acute oral LD50 is >4000mg/kg.
• It is harmful to fish.
• It is stable for at least two years in unopened
containers under normal storage conditions.

43. • It was developed under the code number PP-
588 by ICI Plant protection Division.
• Nirmod is the trade name for it which is
available as E.C (containing 250g per litre) or
W.P.(containing 250 g per kg) formulations.
• It is used for the control of powdery mildew of
fruits and ornamentals. It is commercially
introduced in the year 1975.

44. • On leaf application it is absorbed and shows
translaminar movement and also moves towards
leaf margins.
• It also shows vapour phase activity.
• Control of foliar infection through root drench
application to apple and cucumber seedlings was
quite poor.
• It breaks down to 5-butyl-2-ethylamino-4-
hydroxy-6-methyl pyrimidine in plants, water, soil
and on fruits. In soil half-life is of 6.5 to 7.5
weeks. It further breaks down to a number of
products some of which are non-fungicidal.

45. • It has both protectant and eradicant activity.
At 5 to 15 g a.i. per 100 litres rate, it gives
excellent control of apple powdery mildew.
• It is also effective against powdery mildew of
peach. Rose, cucurbits, vine, apricot, mango,
sugar beet, strawberry, chrysanthemum, pea
and pepper.