Note: Descriptions are shown in the official language in which they were submitted.
,~F/5-20775/A CA 02246424 1998-07-31
PYRIMIDIN-4-ONE DERIVATIVES AS PESTICIDE
The present invention relates to novel pyrimidin-4-one derivatives of formula 1, which have
pesticidal activity, in particular fungicidal activity,
R3 ~ ~ N ~ R~
wherein
R1 = C,-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, each of which is unsubstituted
or substituted by halogen;
R2 = OR5;
R3 and R4 are each independently of the other hydrogen, halogen;
Rs is C1-C6alkyl or C3-C6cycloalkyl each unsubstituted or halogen-substituted; and
A = thienyl.
The invention also relates to the preparation of these compounds, to agrochemical
compositions comprising as active ingredient at least one of these compounds, as well as to
the use of the active ingredients or compositions for pest control, in particular as fungicides,
in agriculture and horticulture.
The compounds I and, optionally, their tautomers may be obtained in the form of their salts.
Because the compounds I have at least one basic centre they can, for example, form acid
addition salts. Said acid addition salts are, for example, formed with mineral acids, typically
sulfuric acid, a phosphoric acid or a hydrogen halide, with organic carboxylic acid~s, typically
acetic acid, oxalic acid, malonic acid, maleic acid, fumaric acid or phthalic acid, with
hydroxycarboxylic acids, typically ascorbic acid, lactic acid, malic acid, tartaric acid or citric
acid, or with benzoic acid, or with organic sulfonic acids, typically methane acid or
p-toluenesulfonic acid.
Together with at least one acidic group, the compounds of formula I can also form salts with
bases. Suitable salts with bases are, for example, metal salts, typically alkali metal salts or
CA 02246424 1998-07-31
alkaline earth metal salts, e.g. sodium salts, potassium salts or magnesiumsalts, or salts
with ammonia or an organic amine, e.g. morpholine, piperidine, pyrrolidine, a mono-, di- or
trialkylamine, typically ethylamine, diethylamine, triethylamine or dimethylpropylamine, or a
mono-, di- or trihydroxyalkylamine, typically mono-, di- or triethanolamine. Where appropri-
ate, the formation of corresponding internal salts is also possible. Within the scope of this
invention, agrochemically acceptable salts are preferred.
Where asymmetrical carbon atoms are present in the compounds of formula 1, these com-
pounds are in optically active form. Owing to the presence of double bonds, the compounds
can be obtained in the [E] and/or [Z] form. Atropisomerism can also occur. The invention
relates to the pure isomers, such as enantiomers and diastereomers, as well as to all
possible mixtures of isomers, e.g. mixtures of diastereomers, racemates or mixtures of
racemates.
The general terms used hereinabove and hereinbelow have the following meanings, unless
otherwise defined:
Alkyl groups are, in accordance with the number of carbon atoms, straight-chain or
branched and will typically be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl,
tert-butyl, n-amyl, tert-amyl, 1-hexyl or 3-hexyl.
Alkenyl will be understood as meaning straight-chain or branched alkenyl such as allyl,
methallyl, 1-methylvinyl or but-2-en-1-yl. Preferred alkenyl radicals contain 3 to 4 carbon
atoms in the chain.
Alkynyl can likewise, in accordance with the number of carbon atoms, be straight-chain or
branched and is typically propargyl, but-1-yn-1-yl or but-1-yn-3-yl. The preferred meaning is
propargyl.
Halogen and halo substituents will be understood generally as meaning fluoro, chloro,
bromo or iodo. Fluoro, chloro or bromo are preferred meanings.
AMENDED Slt~ET
,, CA 02246424 1998-07-31
- 3 -
Haloalkyl can contain identical or different halogen atoms, typically fluoromethyl, difluoro-
methyl, difluorochloromethyl, trifluoromethyl, chloro methyl, dichloromethyl, trichloromethyl,
2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2,2,2-trichloroethyl, 3,3,3-trifluoropropyl.
Cycloalkyl is, depending on the ring size, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or
cycloheptyl .
A is thienyl, including all 3 isomers.
A special group within the scope is that of the compounds of formula 1, wherein
R1 = C3-C6alkyl, cyclopropyl, cyclobutyl;
R2 = ORs;
R3 and R4 are each independently of the other hydrogen, chloro, bromo, iodo;
Rs C2-C6alkyl, cyclopropyl or cyclobutyl (subgroup D).
A preferred group within the scope of subgroup D is that of the compounds of the formula 1,
wherein
A = thienyl[2.3-d],
R1 = C3-C6alkyl,
- R2 = ORs,
R3 and R4 are each independently of the other hydrogen, chloro, bromo, iodo and
Rs = C2-C6alkyl (subgroup E).
The most preferred compounds of the invention disclosed herein are the following ones:
6-Chloro-2-propoxy-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.41),
6-Chloro-2-propoxy-3-isobutyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.42),
6-Chloro-2-isobutoxy-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.83),
6-Chloro-2-propoxy-3-butyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.106), '
6-Bromo-2-propoxy-3-butyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.107),
6-Chloro-2-butoxy-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.112),
6-Bromo-2-butoxy-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.113),
6-Chloro-2-butoxy-3-butyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.129),
6-Bromo-2-butoxy-3-butyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.130),
AMEN~)E~ SH-tET
CA 02246424 1998-07-31
6-Chloro-2-butoxy-3-isobutyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.131),
6-Bromo-2-butoxy-3-isobutyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.132),
6-Bromo-2-propoxy-3-isobutyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.133),
6-Chloro-2-ethoxy-3-isobutyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.134),
6-Bromo-2-ethoxy-3-isobutyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.135),
6-Bromo-2-isobutoxy-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one (No. 2.136).
The compounds of formula I can be prepared as follows:
Scheme 1
/ 1 b) R 1--NCS/DM F or alcohols/75-1 60~C \~
R3~ 2 1a) CSC12 R NCS (~NHcN
R4 COOR ~ 2) H2NR1
I l ~ ;COOR
R COO R _ R4
R =H, C1- C6alkyl 4 111 IV
R4~ R2 ~ ~S--R
R2 = OR5 la V
AMENDED SH~T
CA 02246424 1998-07-31
The compounds of formula I are preferably prepared starting from a-amino-~-carboalkoxy-
heterocycles or a-amino-,~-carbocyclic acid heterocycles, some of which, where Het =
thienyl, are commercially available (2 isomers). The methyi thiophene-2-amino-3-carboxylate can be prepared, for example, in accordance with Acta Pharm. Suecica 1968,
Vol. 5, p.563, according to S.Gronowitz et al. Other heterocycles can be prepared according
to instructions in the literature. The synthesis of, for example, ethyl 5-aminothiazole-4-
carboxylate and ethyl 5-amino-2-methylthiazole-4-carboxylate is described by Golankiewicz
et al. in Tetrahedron 1985, 41, 5989. The reaction of the a-amino-~-
carboalkoxyheterocycles or a-amino-~-carbocyclic acid heterocycles with thiophosgene
(step 1 a in scheme 1 ) is conveniently carried out in the presence of a base, such as NaOH,
KOH, CaCO3, Na2CO3, K2CO3, NaHCO3, N(Et)3, pyridine, and others, in solvents, such as
CH2CI2, CHCI3, ether, tetrahydrofuran and others, possibly in a 2 phase mixture consisting
of CHCI3/water or CH2CI2/water, or toluene/water in the temperature range from 0~C to
reflux temperature. The resulting isothiocyanates are then converted with primary amines,
such as n-butylamine, n-propylamine, isopropylamine, allylamine, propargylamine,cyclopropylamine, and others, in a soivent (ether, tetrahydrofuran, CH 2CI2, CHCI3, benzene,
toluene, dimethylformamide, dimethylsulfoxide) at 0~C to reflux temperature into the
thioureaheterocycies IV (step 2 in scheme 1), which can also be prepared via reaction of
the heterocyclic amines ll with isothiocyanatoalkanes such as 1-isothiocyanatopropane, 1-
isothiocyanatobutane and others in ethanol, n-propanol, n-butanol, dimethylformamide or
dimethylsulfoxide as solvents at temperatures between 50~C and reflux temperature (step
1b in scheme 1). The thioureaheterocycles IV, in most cases, cyclise immediately (step 3 in
scheme 1). In some cases, the cyclysation is carried out in the presence of stronger bases,
such as potassium tert-butylate, sodium hydride or potassium hydride in solvents such as
tetrahydrofuran, dimethylfomamide or dimethylsulfoxide in the temperature range from 20~-
1 40~C. The 2-thioxopyrimidin-4-one derivatives are then deprotonised (using bases such as
NaOH, NaH, KH, n-BuLi, Na2CO3, K2CO3 etc.) and are then S-alkylated by the addition of
alkyihalides (halo = Br, I) (step 4 in scheme 1). The reaction with methyliodide results in the
2-methylsulfanylpyrimidin-4-one derivative which is an important intermediate for the
synthesis of alkoxy-substituted and aminoalkyl-substituted pyrimidin-4-ones. Thereplacement of the thiomethyl group (step 5 in scheme 1 ) with alkoxy is most preferably
carried out by reaction with metal alkoxides, such as NaOMe, NaOEt, NaO-propyl, in the
AMENDED S~T
CA 02246424 1998-07-31
~ ;
. .
corresponding alcohol, tetrahydrofurane or dimethylsulfoxide as solvent in the temperature
range from 20~-1 50~C.
The above synthesis route is the first disclosure of how to prepare 3H-thieno[2.3-d]-
pyrimidin-4-one derivatives within the structural pattern of formula I herein.
The invention also relates to the intermediates of the formula IV and V, and especially to
those wherein A represents thienyl[2.3-d].
The introduction of further substituents into the 5-ring of the thienopyrimidin-4-ones may
also conveniently be carried out using metallorganic methodology. Thieno[3.2-d]-pyrimidin-
4-ones and thieno[2.3-d]pyrimidin-4-ones, for example, can be deprotonised selectively in
6-position. Particularly suitable bases for this purpose are lithium diisopropylamide (LDA),
lithium cyclohexylisopropylamide (LICA), secondary butyl lithium/TMEDA. A great number of
the radicals R3 indicated above can be introduced by reacting the resulting anions with
electrophilics (step 1 in scheme 2), typically Br2, NBS, F2, ICI, Cl2, F+ reagents.
,
Scheme 2: Synthesis of special heterocycles
~N l Rz E1 E ~ ~N~l R E2 E ~ :~ l N l R
X = S
E~1 2 = NBS (N-Bromsuccinimide), NCS (N-Chlorsuccinimide), Cl2, Br, FCI, F+ reagents.
AMENDED SH~t~T
CA 02246424 1998-07-31
Scheme 3: Synthesis of special thienopyrimidin-4-ones (special methods for the intro-
duction of halogen into the thiophene ring)
a) Thieno~2.3-dl~yrimidin-4-ones:
O N-halosuccinimide O
~ ,Rl (or Cl 2 Or Br 2 ) ~ ~N,R1
a1) [~ ~l pyridine/ 0~C - reflux Hai~N R2
1-3 molar equivalents of N-bromosuccinimide or N-chlorosuccinimide (or Cl z gas or Br2) are
used for halogenation. The solvent used is, for example, pyridine in the temperature range
from 0~C to reflux. The reaction time is 1 to 24 hours.
a2) "Pure" chlorinating method:
O , O
J~ ,Rl 1-3 equiv, So2cl2 ~ ~ ,R,
CHCI3 or CH2C12 CIJ~N'lR2
-20~C to +50~C
b) Thieno~3.4-d~pyridin-4-ones:
O O
b1)S~N,R1 N-halosuccinimideS/~N'R~ (12)
N~lR pyridine/ 0~C - reflux H I N~
(see method a1)) a
A~,ENGED Sr~l
CA 02246424 1998-07-31
- 8 -
b2)
s~N' ' 1) LDA/-78~C s~N
N R 2) ClSiMe3 N R2
halog. agent (Br2,
C12,NCS,NBS)
base
solv . (CHCI 3, CH 2C12
pyridine, etc.)
0~C - reflux
o F (KF,CsF or SiMe O
I l tetrabutyl- 1 3 1 l
s~ ,R1 ammonium fluoride)~l Hal1 = Cl,Br
N R THF / 0~C- N
Hal1 2 reflux Hal1 R2
halog. agent (Br2,
C12,NCS or NBS)
Hal2 0
S/~
>=~ --1 Hal2= Cl,Br
Hall R2
Mixed halogenised compounds (hal, different from hal2) can likewise be prepared in the
manner indicated in b2).
AMENDED SltEET
CA 02246424 1998-07-31
g
Another interesting aspect of this application is the use of metallorganic methodology for
the preparation of thieno[3.4-d]pyrimidin-4-ones substituted in 5-position:
Scheme 4
N~ E+ ~ ~N~ E+ ) ~N~
E1 and E2 are as defined in scheme 2.
The described reactions are carried out in per se known manner, e.g. in the presence or
absence of a suitable solvent or diluent or of a mixture thereof, if appropriate with cooling,
at room temperature or with heating, e.g. in the temperature range from about -20~C to the
boiling temperature of the reaction medium, preferably in the range from about -20~C to
about +150~C and, if required, in a closed vessel, under pressure, in an inert gas
atmosphere and/or under anhydrous conditions.
Illustrative examples of such solvents or diluents are: aromatic, aliphatic and alicyclic hydro-
carbons and halogenated hydrocarbons, typically benzene, toluene, xylene, chlorobenzene,
bromobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane,
dichloroethane or trichloroethane; ethers, typically diethyl ether, tert-butylmethyl ether,
tetrahydrofuran or dioxane; ketones, typically acetone or methyl ethylketone; alcohols,
typically methanol, ethanol, propanol, butanol, ethylene glycol or glycerol; esters, typically
ethyl acetate or butyl acetate; amides, typically N,N-dimethylformamide, N,N-
dimethylacetamide, N-methylpyrrolidone or hexamethylphosphoric acid triamide; nitriles,
typically acetonitrile; and sulfoxides, typically dimethylsulfoxide. Bases used in excess, such
as triethylamine, pyridine, N-methylmorpholine or N,N-diethylaniline, can also be-used as
solvents or diluents.
Suitable bases are, for example, alkali metal hydroxide or alkaline earth metal hydroxide,
alkali metal hydride or alkaline earth metal hydride, alkali metal amide or alkaline earth
metal amide, alkali metal alkanolate or alkaline earth metal alkanolate, alkali metal carbo-
nate or alkaline earth metal carbonate, alkali metal dialkylamide or alkaline earth metal
dialkylamide, or alkali metal alkylsilylamide or alkaline earth metal alkylsilylamide, alkyl-
AMEND~n ~HF~T
~ CA 02246424 1998-07-31 - -~
~ ' . .
- 10 -
amines, alkylenediamines, optionally N-alkylated, optionally unsaturated cycloalkylamines,
basic heterocycles, ammonium hydroxides and carbocyclic amines. Examples meriting
mention are sod!um hydroxide, sodium hydride, sodium amide, sodium methanolate,
sodium carbonate, potassiumtert-butanolate, potassium carbonate, lithium diisopropyl-
amide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, triethylenedi-
amine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-
(N,N-dimethylamino)pyridine, N-methylmorpholine, benzyltrimethylammoniumhydroxide, and
1,8-diazabicyclo[5.4.0]undec-5-ene (DBU).
Quinazolinone derivatives having fungicidal properties are known from W0-94/26722 or
EP -A-276825 .
Surprisingly, it has now been found that the novel compounds of formula I have, for
practical purposes, a very advantageous spectrum of activities for protecting piants against
diseases that are caused by fungi as well as by bacteria and viruses.
The compounds of formula I can be used in the agricultural sector and related fields as
active ingredients for controlling piant pests. The novel compounds are distinguished by
excellent activity at iow rates of application, by being well tolerated by plants and by being
environmentally safe. They have very useful curative, preventive and systemic properties
and are used for protecting numerous cultivated plants. The compounds of formula I can be
used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms,
leaves, stems, tubers, roots) of different crops of useful plants, while at the same time
protecting also those parts of the plants that grow later e.g. from phytopathogenic micro-
organisms.
It is also possible to use compounds of formula I as dressing agents for the treatment of
plant propagation material, in particular of seeds (fruit, tubers, grains) and plant cuttings
(e.g rice), for the protection against fungal infections as well as against phytopatii'ogenic
fungi occurring in the soil.
The compounds I are, for example, effective against the phytopathogenic fungi of the
following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium,
Septoria, Cercospora and Alternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia,
Puccinia). Additionally, they are also effective against the Ascomycetes classes (e.g. Ven-
AMENDED SHEl~
CA 02246424 1998-07-31
turia and Erysiphe, Podosphaera, Monilinia, Uncinula) and of the Oomycetes classes (e.g.
Phytophthora, Pythium, Plasmopara). Furthermore, the novel compounds of formula I are
effective against phytopathogenic bacteria and viruses (e.g. against Xanthomonas spp,
Pseudomonas spp, Erwinia amylovora as well as against the tobacco mosaic virus).
Within the scope of this invention, target crops to be protected typically comprise the
following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related
species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears,
plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous
plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers,
coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucum-
bers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit,
mandarins); vegetables (spinache, lettuce, asparagus, cabbages, carrots, onions, tomatoes,
potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco,
nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber
plants, as well as ornamentals.
The compounds of formula I are normally used in the form of compositions and can be
applied to the crop area or plant to be treated, simultaneously or in succession with further
compounds. These further compounds can be e.g. fertilisers or micronutrient donors or
other preparations which influence the growth of plants. They can also be selective herbici-
des as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures
of several of these preparations, if desired together with further carriers, surfactants or
application promoting adjuvants customarily empioyed in the art of formulation.
The compounds of formula I can be mixed with other fungicides, resulting in some cases in
unexpected synergistic activities.
Mixing components which are particularly preferred are azoles such as propicon~zole,
difenoconazole, cyproconazole, epoxiconazole, tebuconazole, tetraconazole, fenbucon-
azole, metconazole, bromuconazole; and also fenpropidine, fenpropimorph, cyprodinile,
pyrimethanile, S-methyl benzo-1,2,3-thiadiazole-7-thiocarboxylate; and strobilurines such as
azoxystrobine and cresoximemethyl.
AMEND~D SHE~F
CA 02246424 1998-07-31
Suitable carriers and adjuvants can be solid or liquid and are substances useful in formula-
tion technology, e.g. natural or regenerated mineral substances, solvents; dispersants,
wetting agents, tackifiers, thickeners, binders or fertilisers.
A preferred method of applying a compound of formula 1, or an agrochemical composition
which contains at least one of said compounds, is foliar application. The frequency of
application and the rate of application will depend on the risk of infestation by the corre-
sponding pathogen. However, the compounds of formula I can also penetrate the plant
through the roots via the soil (systemic action) by drenching the locus of the plant with a
liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular
form (soil application). In crops of water rice such granulates can be applied to the flooded
rice field. The compounds of formula I may also be applied to seeds (coating) by impregna-
ting the seeds or tubers either with a liquid formulation of the fungicide or coating them with
a solid formulation.
The compounds of formula I are used in unmodified form or, preferably, together with the
adjuvants conventionally employed in the art of formulation. To this end they are conve-
niently formulated in known manner to emulsifiable concentrates, coatable pastes, directly
sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders,
dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of
the compositions, the methods of application, such as spraying, atomising, dusting, scatter-
ing, coating or pouring, are chosen in accordance with the intended objectives and the pre-
vailing circumstances.
Advantageous rates of application are normally from 5 g to 2 kg of active ingredient (a.i.)
per hectare (ha), preferably from 10 9 to 1 kg a.i./ha, most preferably from 20 g to 600 g
a.i./ha. When used as seed drenching agent, convenient dosages are from 10 mg to 1 g of
active substance per kg of seeds.
The formulation, i.e. the compositions containing the compound of formula I and, if desired,
a solid or liquid adjuvant, are prepared in knwon manner, typically by intimately mixing
and/or grinding the compound with extenders, e.g. solvents, solid carriers and, optionally,
surface active compounds (surfactants).
AMEND~D SH~ET
CA 02246424 1998-07-31
- 13 -
Suitable solvents may typically be: aromatic hydrocarbons, preferably the fractions con-
taining 8 to 12 carbon atoms such as xylene mixtures or substituted naphthalenes; phtha-
lates such as dibutyl or dioctyl phthalate; aliphatic hydrocarbons such as cyclohexane or
paraffins; alcohols and glycols and their ethers and esters such as ethanol, diethylene
glycol, 2-methoxyethanol or 2-ethoxyethanol; ketones such as cyclohexanone; strongly
polar solvents such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethyl formamide; as
well as vegetable oils or epoxidised vegetable oils such as epoxidised coconut oil or
soybean oil; and water.
The solid carriers typically used for dusts and dispersible powders are usually natural
mineral fillers such as calcite, talcum, kaolin, montmorillonite or attapulgite. To improve the
physical properties it is also possible to add highly dispersed silicic acid or highly dispersed
absorbent polymers. Suitable granulated adsorptive carriers are porous types, including
pumice, broken brick, sepiolite or bentonite; and suitable nonsorbent carriers are materials
such as calcite or sand. In addition, innumerable pregranulated materials of inorganic or
organic origin may be used, typically especially dolomite or pulverised plant residues.
Depending on the compound of formula I to be formulated, suitable surfactants are non-
ionic, cationic and/or anionic surfactants having good emulsifying, dispersing and wetting
properties. Surfactants will also be understood to include surfactant mixtures.
Suitable anionic surfactants may be so-called water-soluble soaps as well as water-soluble
synthetic surface-active compounds.
Illustrative examples of nonionic surfactants are nonylphenol polyethoxyethanols, castor oil
polyglycol ether, polyadducts of polypropylene and polyethylene oxide, tributylphenoxy
polyethoxyethanol, polyethylene glycol and octylphenoxy polyethoxyethanol.
Fatty acid esters of polyoxyethylene sorbitan, such as polyoxyethylene sorbitan ti'ioleate,
are also suitable.
The cationic surfactants are preferably quarternary ammonium salts carrying, as N-sub-
stituent, at least one C8-C22 alkyl radical and, as further substituents, optionally halogenated
lower alkyl, benzyl or hydroxy-lower alkyl radicals.
AMEND~D SH~T
-
CA 02246424 1998-07-31
: .
- 14-
Further surfactants customarily employed in the art of formulation are known to the expert
or can be found in the relevant literature.
The agrochemical formulations will usually contain from 0.1 to 99 % by weight, preferably
from 0.1 to 95 % by weight, of the compound of formula 1, 99.9 to 1 % by weight, preferably
99.8 to 5 % by weight, of a solid or liquid adjuvant, and from 0 to 25 % by weight, preferably
from 0.1 to 25 % by weight, of a surfactant.
Whereas it is preferred to formuiate commercial products as concentrates, the end user will
normally use dilute formulations.
The compositions may also contain further adjuvants such as stabilisers, antifoams,
viscosity regulators, binders or tackifiers as well as fertilisers, micronutrient donors or other
formulations for obtaining special effects.
The following non-iimitative Examples illustrate the above-described invention in more
detail. Temperatures are given in degrees Celsius. The following abbreviations are used: Et
= ethyl; i-propyl = isopropyl; Me = methyl; m.p.= melting point. "NMR" means nuclear
magnetic resonance spectrum. MS = mass spectrum. "%" is percent by weight, unless
corresponding concentrations are indicated in other units.
Preparation Examples:
Example P-1 3-Propyl-2-thioxo-2,3-dihydro-1 H-thieno[3.2-d]pyrimidin-4-one
H
~3~ CH2CH2CH3
In a sulfonation flask, 1.7 g (0.028 mol) of n-propylamine are added dropwise to 30 ml of
tetrahydrofuran and 5.2 g (0.026 mol) of methyl 3-isothiocyanatothiophene-2-carboxylate,
dissolved in 30 ml of tetrahydrofuran, such that the internal temperature does not rise above
35~C. The reaction mixture is then stirred for 16 hours at reflux temperature and the tetra-
hydrofuran is then removed in a waterjet vacuum. The residue is taken up in ethyl acetate
and extracted three times with water. The organic phase is then dried over sodium sulfate
AM~NDED S~l~
CA 02246424 1998-07-31
- 15 -
and the solvent is removed in the water-jet vacuum, giving the 3-propyl-2-thioxo-2,3-di-
hydro-1 H-thieno[3.2-d]pyrimidin-4-one crude product which can be purified by digestion in
tert-butylmethyl ether. The slightly brownish powder (5.3 g) has a melting point of >230~C.
Example P-2 2-Methylsulfanyl-3-propyl-3H-thieno[3.2-d]pyrimidin-4-one
~; CH2CH CH3
In a sulfonation flask, 0.84 g (0.021 mol) of a -60% sodium hydride dispersion is added to
20 ml of absolute tetrahydrofuran, and then 4.8 g (0.021 mol) of 3-propyl-2-thioxo-2,3-
dihydro-1 H-thieno-[3.2-d]pyrimidin-4-one, dissolved in 80 ml of tetrahydrofuran, are added
dropwise such that the internal temperature remains constant at about 25~C. The mixture is
stirred for 1 hour at room temperature and then 4.3 g (0.03 mol) of methyl iodide are added
all at once. The mixture is refluxed for 4 hours and then the tetrahydrofuran is removed in a
waterjet vacuum. The residue is taken up in ethyl acetate and the organic phase is
extracted three times with water. The organic phase is dried over sodium sulfate and the
solvent is removed in the waterjet vacuum, giving the crude product which is purified by
column chromatography over silica gel (eluant: ethyl acetate/hexane 1:3). 2-Methylsulfanyl-
3-propyi-3H-thieno[3.2-d]pyrimidin-4-one is obtained in virtually quantitative yield and having
a melting point of 142-1 44~C.
Example P-3 6-Bromo-2-methylsulfanyl-3-propyl-3H-thieno[3.2-d]pyrimidin-4-one
N~,S--CH3
~ N [cmpd 1.4]
Br S~ CHzCH2CH3
o
In a sulfonation flask, 9.6 g (0.04 mol) of 2-methylsulfanyl-3-propyl-3H-thieno[3.2-d]-pyri-
midin-4-one are added to 200 ml of absolute tetrahydrofuran. Subsequently, 4.07 g
(0.042 mol) of lithium diisopropylamide, dissolved in 50 ml of absolute tetrahydrofuran, are
added dropwise under N2 such that the internal temperature remains constant at about
-78~C. The mixture is stirred for 1 hour at -78~C and then a solution of 8.5 g (0.048 mol) of
N-bromosuccinimide in 40 ml of absolute tetrahydrofuran is added dropwise such that the
AMENDE~ S~ T
CA 02246424 1998-07-31
- 16 -
internal temperature remains constant at about -78~C. The condenser is then removed and
the mixture is slowly warmed to room temperature. The tetrahydrofuran is removed in a
waterjet vacuum and the residue is dissolved in ethyl acetate. The organic phase is
washed with water, dried over sodium sulfate and the ethyl acetate is then removed in the
waterjet vacuum. The crude product is purified by column chromatography over silica gel
(eluant: ethyl acetate/hexane = 1 :5), giving 3.8 9 of 6-bromo-2-methylsulfanyl-3-propyi-3H-
thieno[3.2-d]pyrimidin-4-one in the form of a yellow powder having a melting point of 138-
141~C.
Example P-4 2-Propoxy-3-propyl-3H-thieno[3.2-d]pyrimidin-4-one
N ~ O--CH2CH2CH3
[~ N~ [cmpd 1.40]
S 1~ CH2CH2cH3
o
In a sulfonation flask,1.66 9 (0.02 mol) of sodium propylate and 1.5 g (0.00625 mol) of 2-
methylsulfanyl-3-propyl-3H-thieno-[3.2-d]pyrimidin-4-one are stirred in 50 ml of absolute n-
propanol for 3 hours under N 2 at reflux temperature. The n-propanol is then removed in a
waterjet vacuum and the residue is taken up in ethyl acetate/water and extracted three
times with water. The organic phase is dried over sodium sulfate and the solvent is removed
in the waterjet vacuum, giving the crude product which is then purified by column chroma-
tography over silica gel (eluant: ethyl acetate/hexane 1 :3).1.22 g of 2-propoxy-3-propyl-3H-
thieno[3.2-d]pyrimidin-4-one are obtained in the form of a beige powder having a melting
point of 42-45~C.
Example P-5 7-Chloro-2-propoxy-3-propylthieno[3.4-d]pyrimidin-4-one
,~11~ ,CH2CH2CH3
S>~ l~ [cmpd 3.46] .
Cl N OCH2CH2CH3
In a sulfonation flask, 2.02 g (0.008 mol) of 2-propoxy-3-propylthieno[3.2-d]pyrimidin-
4-one are added, with stirring, to 10 ml of absolute pyridine. The internal temperature is
then raised to 70~C and then 1.60 g (0.012 mol) of N-chlorosuccinimide (NCS) are added
over about 5 min in smallish portions. After stirring for 1 hour at 70-75~C, the pyridine is
AMENDED S~t~T
CA 02246424 1998-07-31
,
- 17-
removed in a waterjet vacuum and the residue is taken up in ethyl acetate. The mixture is
washed repeatedly with dilute aqueous hydrochloric acid, dried over sodium sulfate and
then the solvent is removed in the waterjet vacuum. The crude product so obtained is
purified by column chromatography over silica gel (eluant: n-hexane/ethyl acetate = 9:1),
giving 2.2 g of 7-chloro-2-propoxy-3-propylthieno[3.4-d]pyrimidin-4-one in the form of a
green powder having a melting point of 93-95~C.
Example P-6 Methyl 2-isothiocyanatothiophene-3-carboxyiate
[~~~
S NCS
In a sulfonation flask, 50.2 g (0.32 mol) of methyl 2-aminothiophene-3-carboxylate are
added to 480 ml of chloroform and 320 ml of water. Then 40.5 g (0.35 mol) of thiophosgene
and 1000 ml of saturated aqueous sodium bicarbonate solution are added simultaneously in
40 minutes under stirring. The stirring continued for 1 h at room temperature and then the
organic phase is separated. The water phase is extracted twice with chloroform and the
organic phase dried over sodium sulfate. After removal of the chloroform in the water-jet
vacuum 61.3 g of a dark oil is obtained, which is further purified by column chromatography
over silica gel (eluant: ethyl acetate/hexane_1:5). 41.5 g of methyl 2-
isothiocyanatothiophene-3-carboxylate are obtained in the form of a brown powder having a
melting point of 63-65~C.
Example P-7 (method 1 ) Methyl 2-(3-propylthioureido)thiophene-3-carboxylate
~0~ .
[cmpd 9.1]
S~N
In a sulfonation flask, 13.5 g (0.023 mol) of n-propylamine are added dropwise to 350 ml of
tetrahydrofurane and 41.3 g (0.021 mol) of methyl 2-isothiocyanatothiophene-3-carboxylate,
AMENDED SH~ET
CA 02246424 1998-07-31
such that the internal temperature does not arise above 40~C. The reaction mixture is then
stirred for 4 hours at reflux temperature and then the tetrahydrofurane is removéd in a
waterjet vacuum. The residue is taken up in ethyi acetate and extracted three times with
water. The organic phase is then dried over sodium sulfate and the solvent is removed in
the waterjet vacuum, giving the crude product, which is purified by column chromatography
over silica gel (eluant: ethyl acetate/hexane=1 :3). 32.4 g of methyl 2-(3-propylthioureido)-
thiophene-3-carboxylate are obtained in the form of a beige powder having a melting point
of 123-126~C.
Example P-7 (method 2) Methyl 2-(3-propylthioureido)thiophene-3-carboxylate
In a sulfonation flask, 2.02 g (0.02 mol) of 1-isothiocynatopropane are added dropwise to 30
ml dimethylformamide and 3.0 g (0.019 mol) of methyl 2-aminothiophene-3-carboxylate.
The reaction mixture is then stirred at 130-135~C for 12 hours and after cooling added to
120 ml of water. The resulting mixture is then extracted three times with ethylacetate and
the separeted organic phase dried over sodium sulfate. The solvent is then removed in a
waterjet vacuum, giving the crude product as a dark oil, which is purified by column
chromatography over silica gel (eluant: tert.butylmethylether/hexane=2:3). 2.0 g of methyl 2-
(3-propylthioureido)thiophene-3-carboxylate are obtained in the form of a yellow powder
having a melting point of 122-124~C.
Example P-8 3-Butyl-2-thioxo-2,3-dihydro-1 H-thieno[2.3-d]pyrimidin-4-one
~N [cmpd 10.4]
S N S
H
In a sulfonation flask, 0.2 g (0.0049 mol) of a ca. 60% sodium hydride dispersion;~is added
to 20 ml absolute tetrahydrofurane. Then 1.29 g (0.0047 mol) of methyl 2-(3-butylthio-
ureido)thiophene-3-carboxylate, dissolved in 10 ml absolute tetrahydrofurane are added
dropwise, such that the internal temperature remains constant at about 25~C. The mixture is
stirred at reflux temperature for 3 hours and then the solvent is removed in a waterjet
vacuum and the residue taken up in ethylacetate/water. After addition of acetic acid the
mixture is extracted three times with ethylacetate and the organic phase dried over sodium
AMENGED ~1 !~T
CA 02246424 1998-07-31
~ ..
.
, . . .
- 19 -
sulfate. After removal of the solvent in a water-jet vacuum, 1.06 9 of 3-butyl-2-thioxo-2,3-
dihydro-1 H-thieno[2.3-d]pyrimidin-4-one are obtained in the form of a brown powder having
a melting point of 200-203~C.
Example P-9 2-Methylsulfanyl-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one
o
~'
In a sulfonation flask, 2.9 g (0.072 mol) of a ca. 60% sodium hydride dispersion is added to
50 ml of absolute tetrahydrofurane. Then 17.7 g (0.069 mol) of methyl 2-(3-
propylthioureido)thiophene-3-carboxylate, dissolved in 100 ml of absolute tetrahydrofurane,
are added dropwise, such that the internal temperature remains constant at about 25~C.
The mixture is stirred at reflux temperature for 5 hours and after cooling to room
temperature 10.9 g (0.077 mol) of methyliodide, dissolved in 10 ml of tetrahydrofurane, are
added dropwise. Then the mixture is stirred another 2 hours at reflux temperature. After
completion of the reaction, the tetrahydrofurane is removed in the waterjet vacuum and the
residue taken up in ethyl acetate. The organic layer is washed twice with water and then
dried over sodium sulfate. After removal of the solvent in the water-jet vacuum, the crude
product is obtained, which is purified by digestion in n-hexane. 15.1 g of 2-methylsulfanyl-3-
propyl-3H-thieno[2.3-d]pyrimidin-4-one are obtained in the form of a slightly yellowish
powder having a melting point of 94-96~C.
Example P-10 2-Propoxy-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one
o
~N ~ [cmpd 2.40] ''
In a sulfonation flask, 12.5 g (0.15 mol) of sodium propylate and 12.0 g (0.05 mol) 2-
methylsulfanyl-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one are stirred in 120 ml of absolute
A','..~ !D~3 S~!ET
CA 02246424 1998-07-31 . ~ ~A
- 20 -
n-propanol for 4 hours under nitrogen at reflux temperature. The n-propanol is then
removed in a waterjet vacuum and the residue taken up in ethyl acetate/water and the
organic phase is extracted twice with water. The organic phase is dried over sodium sulfate
and the solvent removed in the waterjet vacuum, giving the crude product, which is then
purified by column chromatography over silica gel (eluant: ethyl acetate/hexane=1:3).
6.7 g of 2-propoxy-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one are obtained in the form of a
brown resin ('H-NMR-data see table 11).
Example P-1 1 6-Chloro-2-propoxy-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one
o
Cl~ IN~ O [cmpd 2.41]
In a sulfonation flask, 10.1 g (0.04 mol) of 2-propoxy-3-propyl-3H-thieno[2.3-d]pyrimidin-4-
one are added with stirring to 50 ml of absolute pyridine. The internal temperature is then
raised to 70-75~C and 9.0 g (0.07 mol) of N-chlorosuccinimid (NCS) are added over about
10 minutes in smallish portions. After stirring for 2 hours at 70-75~C, the pyridine is removed
in a waterjet vacuum and the residue taken up in ethyl acetate. After washing twice with
cold dilute aqueous hydrochloric acid, drying over sodium sulfate and removing the solvent
in a waterjet vacuum, the crude product is obtained. The purification of the crude product is
accomplished by column chromatography over silica gel (eluant: ethyl acetate/hexane=1:5),
giving 7.8 g 6-chloro-2-propoxy-3-propyl-3H-thieno[2.3-d]pyrimidin-4-one in the form of a
white powder having a melting point of 62-65~C.
The compounds of the following Table can also be prepared in analogous manner or by
another method corresponding to those indicated above:
A~.F'~jDE3 ~H~
CA 02246424 1998-07-31
';;
- 21 -
Table 1
R3 s ~/ R
cmpd R2 Rl R3 R4 phys.
No. data
m.p. ~C
1.1 SMe Et H H
1.2 SMe n-propyl H H 142-144
1.3 SMe n-propyl Cl H 118-121
1.4 SMe n-propyl Br H 138-141
1.12 SMe i-propyl H H oil,
' H-NMR
1.13 SMe i-propyl Cl H 91 -93
1.14 SMe i-propyl Br H 93-96
1.19 OMe Et H H
1.20 OMe n-propyl H H
1.21 OMe n-propyl Cl H
1.22 OMe n-propyl Br H
1.23 OMe n-propyl SMe H
1.28 OCF2H n-propyl H H
1.29 OCF2H n-propyl Cl H
1.30 OCF2H n-propyl Br H
1.31 OEt n-propyl H H
1.32 OEt n-propyl Cl H
1.33 OEt n-propyl Br H
1.37 OEt n-propyl F H
1.40 O-n-propyl n-propyl H H 42-45
1.41 O-n-propyl n-propyl Cl H 84-86
1.42 O-n-propyl n-propyl Br H 82
A~ENDEI~ S~E~T
CA 02246424 l998-07-3l
- 22 -
1.50 O-n-propyl i-propyl H H oil,
1H,NMR
1.51 O-n-propyl i-propyl Cl H oil,
' H-NMR
1.52 O-n-propyl i-propyl Br H oil,
1H-NMR
1.58 O-i-propyl n-propyl H H
1.59 O-i-propyl n-propyl Cl H
1.60 O-i-propyl n-propyl Br H
1.61 O-n-propyl n-butyl H H
1.62 O-n-butyl n-butyl H H
1.63 O-n-hexyl n-propyl H H
1.71 SMe CH2CH=CH2 H H
1.72 SMe CH2CH=CH2 Cl H
1.73 SMe CH2CH=CH2 Br H
1.74 SMe CH2C CH H H
1.75 SMe CH2C CH Cl H
1.76 SMe CH2C CH Br H
1.77 SMe cyclopropyl H H
1.78 SMe cyclopropyl Cl H
1.79 SMe cyclopropyl Br H
1.83 O-n-propyl n-propyl I H
1.84 O-n-propyl CH2CH=CH2 H H
1.85 O-n-propyl CH2CH=CH2 Cl
1.86 O-n-propyl CH2CH=CH2 Br H
1.87 O-n-propyl CH2C_CH H H
1.88 O-n-propyl CH2C_CH Cl H
1.89 O-n-propyl CHzC--CH Br H
~M~NDED SHE~T
CA 02246424 1998-07-31
; ~ '
- 23 -
1.90 O-n-propyl cyclopropyl H H
1.91 O-n-propyl cyclopropyl Cl Br
1.92 O-n-propyl cyclopropyl Br H
1.96 O-n-propyl n-butyi Cl H
1.97 O-n-butyl n-butyl Cl H oil
1.98 O-n-propyl n-pentyl H H
1.99 O-n-propyl n-pentyl Cl H
1.100 O-n-butyl n-pentyl H H
1.101 O-n-butyl n-pentyl Br H
AMENDED St~
CA 02246424 1998-07-31
' . .; .' '.
- 24 -
Table 2
~ N ~
cmpd R2 R1 R3 R4 phys.
No. data
m.p. ~C
... . ...... ....... .................. ... .
2.1 SMe Et H H
2.2 SMe n-propyl H H
2.3 SMe n-propyl Cl H
2.4 SMe n-propyl Br H
2.12 SMe i-propyl H H
2.13 SMe i-propyl Cl H
2.14 SMe i-propyl Br H
2.19 OMe Et H H
2.20 OMe n-propyl H H oil,
' H-NMR
2.21 OMe n-propyl Cl H 87-89
2.22 OMe n-propyl Br H
2.28 OCF2H n-propyl H H
2.29 OCF2H n-propyl Cl H
2.30 OCF2H n-propyl Br H
2.31 OEt n-propyl H H oil,
1 H-NMR
2.32 OEt n-propyl Cl H 68-71
2.33 OEt n-propyl Br H 1o3-1o7
2.37 OEt n-propyl F H
2.40 O-n-propyl n-propyl H H resin,
'H-NMR
2.41 O-n-propyl n-propyl Cl H 62-65
2.42 O-n-propyl i-butyl Cl H oil
AMEND~D SH~
CA 02246424 l998-07-3l
- 25 -
2.50 O-n-propyl i-propyl H H oil,
~ 'H-NMR
2.51 O-n-propyl i-propyl Cl H 76-78
2.52 O-n-propyl i-propyl Br H
2.58 O-i-propyl n-propyl H H
2.59 '~:)-i-propyl n-propyl Cl H
2.60 O-i-propyl n-propyl Br H
2.61 O-n-propyl n-butyl H H oil,
' H-NM R
2.62 O-n-butyl n-butyl H H oil,
1H-NMR
2.63 O-n-hexyl n-propyl H H
2.71 SMe CH2CH=CH2 H H
2.72 SMe CH2CH=CH2 Cl H
2.73 SMe CH2CH=CH2 Br H
2.74 SMe CH2C CH H H
2.75 SMe CH2C CH Cl H
2.76 SMe CH2C CH Br H
2.77 SMe cyclopropyl H H
2.78 SMe cyclopropyl Cl H
2.79 SMe cyclopropyl Br H
2.83 O-i-butyl n-propyl Cl H
2.84 O-n-propyl CH2CH=CH2 H H
2.85 O-n-propyl CH2CH=CH2 Cl H
2.86 O-n-propyl CH2CH=CH2 Br H
2.87 O-n-propyl CH2C--CH H H
2.88 O-n-propyl CH2C--CH Cl H
2.89 O-n-propyl CH2C--CH Br H
2.90 O-n-propyl cyclopropyl H H 73-75
v~ !L~ ~
CA 02246424 1998-07-31
- 26 -
2.91 O-n-propyl cyclopropyi Cl Br
2.92 O-n-propyl cyclopropyl Br H 128-130
2.96 OMe . n-propyl F H
2.97 OMe n-butyl H H
2.98 OMe n-butyl Cl H
2.99 OMe i-propyl H H oil
2.100 OEt n-propyl I H
2.101 OEt n-butyl H H oil,
1 H-NMR
2.102 OEt n-butyl Cl H oil,
' H-NMR
2.103 OEt n-pentyl H H
2.104 OEt n-pentyl Br H
2.105 O-n-propyl n-propyl I H 93-95
2.106 O-n-propyl n-butyl Cl H 82-84
2.107 O-n-propyl n-butyl Br H 68-70
2.108 O-n-propyl n-butyl I H 80-82
2.111 O-n-butyl n-propyl H H oil,
' H-NM R
2.112 O-n-butyl n-propyl Cl H 49-51
2.113 O-n-butyl n-propyl Br H 59-64
2.118 SMe n-butyl H H oil,
' H-NMR
2.129 O-n-butyl n-butyl Cl H oil
2.130 O-n-butyl n-butyl Br H oii
2.131 O-n-butyl i-butyl Cl H
2.132 O-n-butyl i-butyl Br H
2.133 O-n-propyl i-butyl Br H
2.134 O-ethyl i-butyl Cl H
2.135 O-ethyl i-butyl Br H
2.136 O-i-butyl n-propyl Br H
2.137 O-n-propyl i-butyl Cl H oil
2.138 O-n-propyl i-butyl Br H oil
CA 02246424 l998-07-3l '~ '
- 27 -
Table 3
R4
~ N~, 2
R)~N~R1
3 O
cmpd R2 R1 R3 R4 phys.
No. data
m.p. ~C
3.1 SMe Et H ~ H
3.2 SMe n-propyl H H 130-133
3.3 SMe i-propyl H H
3.4 SMe n-butyl H H
3.5 SMe n-propyl Cl Cl
3.6 SMe n-propyl Br Br
3.7 OMe n-propyl H H
3.8 OMe n-propyl Cl Cl
3.9 OMe n-propyl Br Br
3.10 OEt n-propyl H H
3.11 OEt n-propyl Cl Cl
3.12 O-n-propyl n-propyl H H oil,
1H-NMR
3.13 O-n-propyl i-propyl H H
3.14 O-n-propyl n-propyl Cl Cl
3.15 O-n-propyl n-propyl Br Br 90-93
3.16 O-n-propyl i-propyl Cl Cl oil
3.17 O-n-propyl n-propyl F F
3.18 O-n-propyl n-butyl H H
3.19 O-i-propyl n-propyl H H
3.20 O-i-propyl n-propyl Cl Cl
3.21 O-i-propyl n-propyl Br Br
AMEN~ED SH~
CA 02246424 l998-07-3l
- 28 -
3.22 O-n-butyl n-propyl H H
3.23 O-n-butyl i-propyl H H
3.26 SMe . Cl Cl H
3.27 SMe Br Br H
3.28 SMe CH2CH=CH2 H H
3.29 SMe CH2CH=CH2 Br H
3.30 SMe CH2C_ CH H H
3.31 SMe CH2C--CH Br H
3.32 SMe H H H
3.33 SMe Cl Cl H
3.36 O-n-propyl n-propyi Cl H
3.37 O-n-propyl n-propyl Br H
3.38 O-n-propyl CH2CH=CH2 H H
3~39 O-n-propyl CHzCH=CH2 Br H
3.40 O-n-propyl CH2C_ CH H H
341 O-n-propyl CH2C--CH Br H
3.42 O-n-propyl cyclopropyl H H
3.43 O-n-propyl cyclopropyl Cl H
3.46 O-n-propyl n-propyl H Cl 93-95
3.47 O-n-propyl n-propyl H Br 91-93
3.51 O-n-butyl n-propyl H H 70-71
3.52 O-n-butyl n-propyl H Br
3.53 O-n-butyl n-butyl H H
3.54 O-n-butyl n-butyl H Cl
A.'~.1EN~E~ SHE~T
CA 02246424 l998-07-3l ~ .
- 29 -
Table 9
J~o~R
R S NH IV'
S~ NH
cmpd R R, R3 phys.
No. data
m.p. ~C
9.1 Me n-propyl H 123-126
9.2 Et n-propyl H
9.3 n-propyl n-propyl H
9.4 Me n-propyl Cl .
9.5 Me n-propyl Br
9.6 Me n-butyl H 109-1 11
9.7 Et n-butyl H
9.8 Me n-butyl Cl
9.9 Me n-butyl Br
9.10 Me n-pentyl H 80-82
9. 11 Me n-hexyl H
~ENOEO S~
CA 02246424 1998-07-31
- 30 -
Table 1 0
, ~ ~
R3 S N S
H
cmpd R, R3 phys. Data
No. m.p. ~C
10.1 n-propyl H 224-228
10.2 n-propyl Cl
10.3 n-propyl Br
10.4 n-butyl H 200-203
10.5 n-butyl Cl
10.6 n-butyl Br
10.7 n-pentyl H 195-198
10.8 n-hexyl H
A~E~DED Stt~T
.
CA 02246424 1998-07-31
Table 11
Ex. No. 'H-NMR data (ppm/multiplicity/number of protons); solvent CDCI3
1.12 1.47/d/6H; 4.06/s/3H; 5.48/m/1H; 6.96/d/1H; 7.34/d/1H
1.51 1.08/V3H; 1.48/d/6H; 1.86/m/2H; 4.38/m/2H; 5.48/m/1H; 6.94/s/1H
1.52 1.07/V3H; 1.48/d/6H; 1.86/m/2H; 4.48/m/2H; 5.49/m/1 H; 7.09/s/1 H
2.20 0.97/V3H; 1.69/m/2H; 4.03/V2H; 4.07/s/3H; 6.98/d/1 H; 7.36/d/1 H
2.31 0.96/V3H; 1.47/V3H; 1.69/m/2H; 4.04/V2H; 4.50/q/2H; 6.95/d/1 H; 7.34/d/1 H
2.40 0.97/V3H; 1.06/V3H; 1.70/m/2H; 1.85/m/2H; 4.04/V2H; 4.40/V2H; 6.96/d/1H;
7.34/d/1 H
2.61 0.96/V3H; 1.07/V3H; 1.39/m/2H; 1.70/m/2H; 1.85/m/2H; 4.10/V2H; 4.39/V3H;
7.12/d/1 H; 7.68/d/1 H
2.62 0.93-1.03/2xV6H; 1.37-1.83/ml8H; 4.07/V2H; 4.44/V2H; 6.95/d/1 H; 7.33/d/1 H
2.99 1.47/d/6H; 4.07/s/3H; 5.481sll H; 6.95/d/1 H; 7.34/d/1 H
2.101 0.96/V3H; 1.34-1.45/m/5H; 1.65/m/2H; 4.07/V2H; 4.48/q/2H; 6.95/d/1H;
7.34/d/1 H
2.102 0.95/V3H; 1.33-1.43/m/5H; 1.63/m/2H; 4.05/V2H; 4.47/q/2H; 7.16/s/1H
2.111 0.93-1.03/2xV6H; 1.44-1.831m/6H; 4.04/V2H; 4.44/V2H; 6.95/d/1 H; 7.34/d/1 H
2.118 0.98/V3H; 1.41 /m/2H; 1.75/m/2H; 2.62/s/2H; 4.12/V2H; 7.05/d/1 H; 7.38/d/1 H
3.12 0.96/V3H; 1.05/V3H; 1.68/q/2H; 1.83/q/2H; 3.99/V2H; 4.36/V3H; 7.15/d/1H;
8.17/d/1 H
A~/lE,''lOED St.'i-~T
CA 02246424 1998-07-31 . . .
~,. ~
- 32 -
Formulation Examples for compounds of formuia I
Example F-1.1 to F-1.3: Emulsifiable concentrates
Components F-1. 1 F-1 .2F-1.3
compound of Tables 1 to 3 25% 40% 50%
calcium dodecylbenzenesulfonate 5% 8% 6%
castor oil polyethylene glycol ether
(36 mol ethylenoxy units) 5%
tributylphenolpolyethylene glycol ether
(30 mol ethylenoxy units) - 12% 4%
cyclohexanone - 15% 20%
xylene mixture 65% 25% 20%
Emulsions of any desired concentration can be prepared by diluting such concentrates with
water.
Example F-2: Emulsifiable concentrate
Components F-2
compound of Tables 1 to 3 10%
octylphenolpolyethylene glycol ether
(4 to 5 mol ethylenoxy units) 3%
calcium dodecylbenzenesulfonate 3%
castor oil polyglycol ether
(36 mol ethylenoxy units) 4%
cyclohexanone 30%
xylene mixture 50%
~M'~DED ~ii l~T
CA 02246424 1998-07-31
- 33 -
Emulsions of any desired concentration can be prepared by diluting such concentrates with
water.
Examples F-3.1 to F-3.4: Solutions
Components F-3. 1 F-3.2 F-3.3 F-3.4
compound of Tables 1 to 3 80% 10% 5% 95~~0
propylene glycol monomethyl ether 20%
polyethylene glycol (relative molecular
mass: 400 atomic mass units) - 70%
N-methylpyrrolid-2-one - 20%
epoxidised coconut oil - - 1% 5%benzin (boiling range: 160-190~) - - 94%
The solutions are suitable for use in the form of microdrops.
Examcles F-4.1 to F-4.4: Granulates
Components F-4.1 F-4.2 F-4.3 F-4.4
compound of Tables 1 to 3 5% 10% 8% 21%
kaolin 94% - 79% 54%
highly dispersed silicic acid 1% - 13% 7%
attapulgite - 90% - 18%
The novel compound is dissolved in dichloromethane, the solution is sprayed onto the
carrier and the soivent is then removed by distillation under vacuum.
AMENDED S~ET
.
CA 02246424 1998-07-31
- 34 -
ExamPles F-5.1 and F-5.2: Dusts
Components F-5. 1 F-5.2
compound of Tables 1 to 3 2% 5%
highly dispersed silicic acid 1% 5%
talcum 97%
kaolin 90%
Ready for use dusts are obtained by intimately mixing all components.
Exampies F-6.1 to F-6.3: Wettable powders
Components F-6. 1 F-6.2 F-6.3
compound of Tables 1 to 3 25% 50% 75%
sodium lignin sulfonate 5% 5%
sodium lauryl sulfate 3% - 5%
sodium diisobutylnaphthalene sulfonate - 6% 10%
octylphenolpolyethylene glycol ether
(7 to 8 mol ethylenoxy units) - 2%
highly dispersed silicic acid 5% 10% 10%
kaolin 62% 27%
All components are mixed and the mixture is thoroughly ground in a suitable mill to give
wettable powders which can be diluted with water to suspensions of any desired
concentration .
AMENDED Sl'.~T
CA 02246424 1998-07-31
Biological Examples: Funqidical actions
B-1: Action against Puccinia qraminis on wheat
a) Residual-Protective action
6 days after sowing, wheat plants are sprayed to drip point with an aqueous spray mixture
(0.02% active ingredient) prepared from a wettable powder formulation of the test com-
pound and infected 24 hours later with a uredo spore suspension of the fungus. After an
incubation time of 48 hours (conditions: 95 to 100 % relative humidity at 20~C), the plants
are stood at 22~C in a greenhouse. Evaluation of fungal infestation is made 12 days after
infection .
b) Systemic action
Wheat plants are drenched 5 days after sowing with an aqueous spray mixture
(0.006% a.i., based on the volume of the soil) prepared from a wettable powder formulation
of the test compound. Care is taken that the spray mixture does not come into contact with
the growing parts of the plants. After 48 hours, the plants are infected with a uredospore
suspension of the fungus. After an incubation period of 48 hours (conditions: 95 to 100 %
relative humidity at 20~C), the plants are stood at 22~C in a greenhouse. Evaluation of the
fugal infestation is made 12 days after infection.
Compounds of Tables 1-3 show good activity.
ExamPle B-2: Action against Colletotrichum lagenarium on cucumbers
After a growth period of 2 weeks, cucumber plants are sprayed with an aqueous spray
mixture (concentration 0.002%) prepared from a wettable powder formulation of the test
compound and infected 2 days later with a spore suspension (1 .5x10 5 spores/ml) of the
fungus and incubated for 36 hours at 23~C and high humidity. Incubation is then continued
at normal humidity and c. 22~C. Evaluation of the fungal infestation is made 8 days after
infection .
The compounds of the Tables 1-3 show good activity.
Example B-3: Residual-Protective action against Venturia inaequalis on apPles
Apple cuttings with fresh shoots 10 to 20 cm long are sprayed to drip point with a spray
mixture (0.02% a.i.) prepared from a wettable powder formulation of the test compound.
The plants are infected 24 hours later with a conidia suspensionn of the fungus. The plants
0 S~
CA 02246424 1998-07-31
are then incubated for 5 days at 90 to 100 % relative humidity and stood in a greenhouse
for a further 10 days at 20 to 24~C. Evaluation of the fungal infestation is made 12 days
after infection.
Compounds of Tables 1-3 show good activity.
Example B-4: Action against ErysiPhe qraminis on barley
a) Residual-protective action
Barley plants about 8 cm in height are sprayed to drip point with a spray mixture (0.02% a.i.)
prepared from a wettable powder formulation of the test compound, and the treated plants
are dusted with conidia of the fungus 3 to 4 hours later. The infected plants are stood in a
greenhouse at 22~C. Evaluation of the fungal infection is made 12 days after infection.
b) Systemic action
Barley plants about 8 cm in height are drenched with an aqueous spray mixture
(0.002% a.i., based on the volume of the soil) prepared from a wettable powder formulation
of the test compound. Care is taken that the spray mixture does not come into contact with
the growing parts of the plants. The treated plants are dusted 48 hours later with conidia of
the fugus. The infected plants are then stood in a greenhouse at 22~C. Evaluation of the
fungal infestation is made 12 days after infection.
Compared with the control plants, infestation of the plants treated with compounds of
formula 1, for example the compounds 1.40,1.41,1.42,1.50,1.51,1.52,1.97,2.20, 2.21,
2.31, 2.32, 2.33, 2.40, 2.41, 2.42,2.50,2.51,2.61, 2.62, 2.83, 2.90, 2.92, 2.99, 2.101,
2.102, 2.105, 2.106, 2.107, 2.108, 2.111, 2.112, 2.113, 2.129, 2.130, 2.131, 2.132, 2.133,
2.134, 2.135, 2.136, 3.12, 3.15,3.16, 3.46,3.47 and 3.51, is 20 % or less. The following
compounds exhibit superior activities (no infestation at all): 2.41, 2.42, 2.83, 2.106, 2.107,
2.112, 2.113, 2.129, 2.130, 2.131, 2.132, 2.133, 2.134, 2.135, 2.136.
Example B-5: Action aqainst Podosphaera leucotricha on aPPle shoots
Apple cuttings with fresh shoots about 15cm long are sprayed with a spray mixture
(0.06% a.i.). The plants are infected 24 hours later with a conidia suspension of the fungus
and stood in a climatic chamber at 70% relative humidity and 20~C. Evaluation of the fugal
infestation is made 12 days after infection.
p~ENoE3 St'~t
CA 02246424 1998-07-31 ~.
;'
- 37 -
Compounds of Tables 1-3 show good activity. The following compounds exhibit especially
strong efficacy: 2.41, 2.42, 2.83, 2.106, 2.107, 2.112, 2.113, 2.129, 2.130, 2.131, 2.132,
2.133, 2.134, 2.135, 2.136 (0-5% infestation).
Example B-6: Action aqainst Plasmopara viticola on vines
a) Residual-preventive action: Vine cuttings of the Chasselas variety are raised in a
greenhouse. At the 10-leaf stage, 3 plants are sprayed with a spray mixture (200 ppm a.i.).
After the spray coating has dried, the plants are infected uniformly on the underside of the
leaves with a spore suspension of the fungus. The plants are then kept in a humidty
chamber for 8 days, after which time marked symptoms of disease are observed on the
control plants. The number and size of the infected areas on the untreated plants act as an
indicator of the efficacy of the tested compounds.
b) Curative action: Vine cuttings of the Chasselas variety are raised in a greenhouse and
sprayed at the 10-leaf stage on the underside of the leaves with a spore suspension of
Plasmopara viticola. After 24 hours in the humidity chamber, the plants are sprayed with a
spray mixture (200 ppm a.i.). The plants are then kept for another 7 days in the humidity
chamber. After this time the control plants exhibit symptoms of the disease. The number
and size of the infected areas on the untreated plants act as an indicator of the efficacy of
the tested compounds.
Compoundas of Tables 1-3 show good efficacy.
Example B-7: Action a~ainst Uncinula necator on vines
5 week old vine cuttings are sprayed with a spray mixture (200 ppm a.i.) prepared from a
wettable powder formulation of the test compound.The plants are infected 24 hours later by
conidias from strongly infested vine leafs that are shaken off over the test plants. The plants
are then incubated at 26~C and 60% relative humidity. The evaluation of the fungal
infestation is made ca. 14 days after infection.
Compared with the control plants, infestation of the piants treated with compounds of
formula 1, for example the compounds 1.40, 1.41, 1.42,1.50,1.51, 1.52,1.97, 2.20, 2.21,
2.31, 2.32, 2.33, 2.40, 2.41, 2.42, 2.44, 2.50, 2.51, 2.61, 2.62, 2.83, 2.90, 2.92, 2.99, 2.101,
2.102, 2.105, 2.106, 2.107, 2.108, 2.111, 2.112, 2.113, 2.129, 2.130, 2.131, 2.132, 2.133,
2.134, 2.135, 2.136, 3.12, 3.15, 3.16, 3.46, 3.47 and 3.51, is 20 % or less. The following
p~~~0~9 S~
~ _ .
CA 02246424 1998-07-31
compounds exhibit superior activities (no infestation at all): 2.41, 2.42, 2.83, 2.106, 2.107,
2.112, 2.113, 2.129, 2.130, 2.131, 2.132, 2.133, 2.134, 2.135, 2.136.
,N~) S'~c~
