Note: Descriptions are shown in the official language in which they were submitted.
-1- 21489-G852E
This is a divisional application of the application
Serial No. 496,211 filed November 26, 1985.
The parent application relates to novel 3-cyano-4-
phenyl-pyrroline derivatives having microbi.cidal activity, to
~ompositions containing ~hese active substances as active
components, ancl to ~he use of the active substances or of
compositions containing them for controlling harmful micro-
organisms, particularly phytopathogenic fungi and bacteria. The
parent application relates also to the production of these novel
compounds. This applicakion relates to novel compounds of the
formula ~II)
~ N R
J ~ ~H ~ a CH - N\ (II),
n H - NO R2
useful as intermediates for the synthesis of the compounds o~
formula (I).
The novel compounds o the parent application correspond
to the general formula (I)
~ 3 CN , I),
wherein
R is halogen, Cl-C6-alkyl or Cl-C6-haloalkyl, and n is 0~ 1 or 2.
By the term `alkyl' itself or alkyl or as constituent of
haloalkyl are meant for example the following straight-chain or
branched-chain groups: methyl, e~hyl, propyl, butyl, pentyl or
hexyl, as well as isomers thereof, for example isopropyl, iso-
butyl, sec-butyl, tert-butyl, isopentyl, neopentyl and isopentyl.
6~ i9
Halo as a part of the substituent haloalkyl denotes
the single or multiple occurrence of fluorine, chlorine,
bromine or iodine, preferably fluorine, chlorine or
bromine, in the alkyl group. Such halogenated alkyl groups
are for example: CH2Cl, CH2F, CHC12, CHF2, CH2CH2Br,
C2C15, CH2Br or CHBrCl, preferably CF3.
Preferred compounds of the formula I are those in
which R is chlorine, bromine or methyl, and n is 1 or 2.
Particularly preferred compounds of the formula I
are those in which R is chlorine or methyl, and n is 2.
A preferred individual compound is 3-cyano-4-
(2',3'-dichloropllenyl)- ~2-pyrroline.
The compo~lnds of ~he ~ormulcl I are procluced according
to the invention ~y reducing compounds of the formula II
RX , / 8H2--NO2 N/R (II)
to compounds of the formula III
, Rn n 8H2 -- NHz N~z (III)
in which Rl and R2 independently of one another are each
Cl-C4-alkyl, preferably methyl, or together with the
adjacent nitrogen atom are pyrrolidinyl or piperidinyl,
or with an additional oxygen atom are morpholinyl, .
and Rn has the meaning defined under the formula I;
and subsequently cyclising the products obtained to
compounds of the Eormula I.
The reduction is effected in organic solvents at
elevated temperature, under hydrogen pressure, in the
presence of a catalyst.
&8~
-- 3
Elevated temperatures and optionally the presence
of a weakly acld ~edium are required for the ring
closure reaction.
The reaction medium can be selected from the group
comprising the following solvents: aliphatic and aromatic
hydrocarbons, for example benzene, toluene, the xylenes
or petroleum ether; esters, such as ethyl acetate, propyl
acetate or butyl acetate; ethers and ethereal compounds,
for example dialkyl ether, such as diethyl ether,
diisopropyl ether, tert-butylmethyl ether or, for example,
anisole and in particular cyclic etllers, such as dioxane
or tetrahydrofura~; and al.collols, for exarnple allcanol~;,
5uch as methanol flncl ethanol. ~lso sLIitable are mLxture~
o~ ~uch solven~s.
The process according to the invention is performed
at a temperature of between 0 and 150C. The preferred
range for the reduction reaction is between 15 and 110C.
The ring closure reaction is carried out preferably at
a temperature of between 50 and 150C.
The reduction reaction is generally performed by
catalytic methods. Catalysts suitable for this purpose
are for example platinum, palladium, rhodium, cobalt
polysulfide or Raney nickel. Preferred catalysts are those
formed from platinum/ac~ive charcoal and cobalt
polysulfide.
The hydrogen pressures used for the reduction process
are in general between 1 and 150 bar initial pressure,
measured at room temperature. Hydrogen pressures of
between 2 and 120 bar are preferred for the reduction. ~
It is advantageous in the process described in the
foregoing for producing compounds of the formula I when
~5~
the reduction of the compounds of the formula II and the
cyclisation of the reduced compounds of the formula III
are carried out in one single reaction step. This reaction
procedure constitutes a preferred embodiment of the
process according to the invention. The reaction
temperatures are in this case between 15 and 150~.
The compounds of the formula II used as intermediates
for the synthesis according to the invention are novel.
They are produced by reacting, at elevated temperature and
in inert solvents, compounds of the formula IV
r~X ~' - Cll= C~l- N0z (IV)
with compounds of the formula V
Rl
NC - CH = CH - N~ (V)
R2
in which Rl and R2 independently of one another are each
Cl~C4-alkyl, preferably methyl, or together with the
adjacent nitrogen atom are pyrrolidinyl or piperidinyl
or with an additional 0 atom are morpholinyl, and R and n
have the meanings defined under the formula I.
Suitable solvents are aliphatic and aromatic
hydrocarbons, for example benzene~ toluene, the xylenes
or petroleum ether, preferably toluene; also ethers, such
as dioxane or tetrahydrofuran, especially tetrahydrofuran;
and also alcohols, for example methanol or ethanol,
particularly ethanol. Also applicable are mixtures of
such solvents with one another, as well as mixtures of
the solvents with water.
~4
~ 2 5 ~
The process for producing compounds of the formula II
is performed at temperatures of between 0 and 200C,
preferably between 40 and 130C.
The compound of the formula IV serving as starting
material for the reaction described in the foregoing is
likewise novel. It can be produced by reacting compounds
of the formula VI
RX.n./ CH0 (VI),
in which R and n have the meanings clefined under the
formula I, witll nitromethane in t~le presence o~ ammotlium
acetate in glacial acetic acLd~ at a temperclture of
l~e~ween 70 and 130C.
The benzaldehydes of the formula VI are generally
known and can be produced by known methods.
The novel compounds of the formula II
H - ~ = CH - ~ (II)
I n H2 - Mo2 ~R2
in which Rl and R2 independently of one another are each
Cl-C4-alkyl, preferably methyl, or together with the
adjacent nitrogen atom are pyrrolidinyl or piperidinyl,
or with an additional oxygen atom are morpholinyl,
are valuable intermediates for the production according
to the invention of the novel microbicidally active
compounds of the formula I and hence form a part of the
present inventlon.
Further subject matter of the present invention relates
to the production of compounds of the formula VII
~5~ ''3
-- 6 --
CN
Rn~ (VII),
!
in which Rn has the meanings defined under the formula I,
which are obtainable by oxidation of the novel compounds
of the formula I. The oxidation process is performed
by means of bromine, or in the presence of a catalyst
acting as the oxidising medium, in an inert solvent at
a temperature oE ~etween 0 and 250C. Wi~h the use o~
bromine, temperatures of 0 to 80C are preferred, and
witll the use of a catalyst ~he pre~erred temperaturec. are
150 to 250C. rr~e catalys~ used are those whic~l ale
suitable for oxidising reactions (hydrogen trans~er),
palladium/active charcoal being preferred.
Suitable as catalysts are also polyvalent metal cations.
Technically very advantageous cations are Cu+~ and
particularly Fe++~. Preferred salts are especially FeC13
and FeBr3~
In the oxidation process, air or oxygen is passed
through the reaction mixture, or is introduced under
pressure (e.g. 2 to 120 bar) in an autoclave~ Suitable
solvents are water or aqueous solvent mixtures with
alcohols (methanol, ethanol, isopropanoL, and so forth);
dioxane or tetrahydrofuran, dimethyl sulfoxide; dimethyl
formamide~ or other solvents miscible with water. The
temperature range for oxidation by air in the presence of
metal salts is as a rule 0 to 90C, preferably 5 to 80C.
Some compounds of the formula VII are known~ for
example from the German Offenlegungsschrift No. 2,927,480.
~L25~816~
-- 7 ~
It is stated therein that they have phytofungicidal
properties.
The novel pyrroline derivatives of the formula I
according to the present invention constitute a valuable
enlargement of the prior art, for it has been established
that the compounds of the formula I surprisingly exhibit
a microbicidal spectrum against phytopathogenic fungi and
bacteria which is very favourable for agricultural
requirements. They not only can be used in arable farming
or in similar ields o application for controlling harmful
microorganisms on cultivated plants, but can be additionally
used, in the pro~ection o~ stocks, or preserving perishable
goods. Compouncls o~ tlle ormula I have very advanta~eous
curatlve, ~yst~mic and in p~r~icular preven~ive prope~r~l~s,
and can be used for the protection of numerous, especially
arable, crops. The microorganisms occurring on plants or on
parts of plants (fruit, blossom, foliage, stalks, tubers
or roots) of various cultivated crops can be inhibited or
destroyed with the active substances of the formula I, and
also parts of plants subsequently growing remain preserved
from such microorganisms.
The active substances are eective for example against
the phytopathogenic fungi belonging to the following
classes: Ascomycetes, for example Erysiphe, Sclerotinia,
Fusarium, Monilinia and Helminthosporium; Basidiomycetes,
or example Puccinia, Tilletia and Rhizoctonia; and also
against the Oomycetes belonging to the Phytomycetes class,
such as Phytophthora. As plant protective agents, the
compounds of the formula I can be applied with a particularly
high degree of success against important harmful fungi from
the Fungi imperfecti family, for example against Cercospora or
Piricularia, and especially against Botrytis. Botrytis spp.
~;~56
-- 8 --
(B. cinera, B. allii) constitute with botrytis disease
on grapevines, strawberries, apples, onions and other fruit
and vegetable varieties a significant economic loss
factor. Furthermore, some compounds of the formula I
can be successfully used for protecting perishable goods
of vegetable or animal origin. They combat mould fungi,
such as Penicillium, Aspergillus, Rhizopus, Fusarium,
Helminthosporium, Nigrospora and Alternaria, as well as
bacteria, such as butyric acid bacteria, and yeasts,
such as Candida.
As plant protective agents, the compoun~s of tlle
formula I exhibit, for practical application in
agriculture, a very favourable spectrum of activity for
protecting cultivated plants, without disadvantageously
aEecting these by undesirable side e~ects.
T~e compounds can also be used as clressing age~ts for
the treatment o~ seed (i:ruits, tubers or grain), and of
plant cuttings to protect them from fungus infections,
and also against phytopathogenic fungi occurring in the soil.
The invention thus relates also to microbicidal
compositions, and to the use of the compounds of the
formula I for controlling phytopathogenic microorganisms,
especially fungi which damage plants, and for preventing
an infestation on plants and on provisions of vegetable
or animal origin.
In addition, the present invention embraces also the
production of agrochemical compositions, whereby the
active ingredient is intimately mixed with one or more
substances or groups of subs~ances described herein. Also
included is a process for treating plants or stored
provisions, which process comprises the application of the
:L25~
compounds of the formula I, or of the novel compositions,
to the plants or parts of plants, or to the locus or the
substrate thereof.
Within the scope of this invention, target crops ~or
plant protection are for example the following varieties
of plants: cereals (wheat, barley, rye, oats, rice,
sorghum and related cereals); beet ~sugar beet and fodder
beet); pomaceous fruit, stone fruit and soft fruit
~apples, pears, plums, peaches, almonds, cherries,
strawberries, raspberries and blackberries); legumes
(beans, lentils, peas and soya-beans); oil plants (rape,
mustclrd, poppy, olives, sun~lowers, coco, castor-oil plants,
cocoa and groundnuts); Curcurbitacea (pumplcins, cucumbers
~n~l melons); ~ibre plants (cotton, ~lax) hemp and jute);
citrus fruits (oranges, lemons, grapefruit and manclarins);
varieties of vegetables (spinach, lettuce, asparagus,
varieties of cabbage, carrots, onions, tomatoes, potatoes
and paprika); laurel plants (avocada, cinnamon and
camphor); or plants such as maize, tobacco, nuts, coffee,
sugar cane, tea, grapevines, hops, bananas and natural
rubber plants; and also ornamental plants (composites).
As protective agents for stored products, the compounds
of the ~ormula I are used either in an unmodified form
or preferably together with auxiliaries customarily
employed in formulation practice, and are thus processed,
in a known manner, for example into the form of emulsion
concentrates, brushable pastes, directly sprayable or
dilutable solutions, diluted emulsions, wettable powders,
soluble powders, dusts or granulates, and also encapsu-
lations in for example polymeric substances. The application
processes, such as spraying, scattering, brushing or
pouring, and likewise the type of composition, are selected
1~5~869
- 10 -
to suit the objectives to be achieved and the prevailing
conditions. Favourable applied amounts are in general
0.01 to at most 2 kg of active ingredient per 100 kg of
substr~te to be protected; the amounts depend however
quite considerably on the nature (extent of surface area,
consistency, and moisture content) of the substrate and on
environmental influences thereon.
Within the scope of the present invention, stored
stocks and provisions are vegetable and/or animal natural
materials and products from further processing, for example
the plants which are listed in the following and which
have been taken out from the natural life cycle, and parts
of these ~lants (stalks, leaves, tubers, seeds, frwits and
grains), the m~teri~l.s bein~ h~ ~reshly llarves~ecl
condi~ion or in tlle forlll resulting Erom further processing
(pre-dried, moistened, crushed, ground or roasted). The
following productive materials may be given as examples,
which however have no limiting character with respect to the
scope of this invention: cereals (such as wheat, barley,
rye, oats, rice, sorghum and related cereals); beet (such
as carrots, sugar beet and fodder beet); pomaceous fruit,
stone fruit and soft fruit (such as apples, pears, plums,
peaches, almonds, cherries, strawberries, raspberries and
blackberries); legumes (such as beans, lentils, peas ancl
soya-bean); oil plants (such as rape, mustard, poppy,
olives, sunflowers, coco, castor-oil plants, cocoa and
groundnuts); Cucurbitacea (such as pumpkins, cucumbers and
melons); fibre plants (such as cotton, flax, hemp, jute
and nettles); citrus fruits; varieties of vegetables (such
as spinach, lettuce, asparagus and varieties of cabbage,
onions, tomatoes, potatoes and paprika); laurel plants
(such as avocada, cinnamon and camphor); or plants such as
maize, tobacco, nuts, coffee, sugar cane, tea, grapevines,
~2~ 369
- 11 -
chestnuts, hops, bananas, grass and hay.
Natural products of animal origin which may be mentioned
are in particular dried processed meat and fish products,
such as dried meat, dried fish, meat concentrates, bone
meal, fish meal and dried animal feed.
By treatment with compounds of the formula I, the
treated stored products are lastingly protected against
infestation by mould fungi and other undesirable micro-
organisms. Consequently, the formation of toxic and
in part carcinogenic mould fungi (aflatoxines and
ochratoxines) is prevented, the material is kept from
decomposing, and the quality thereof is main~ained hLgh
~or a prolonged perlod o~ tlme. The process accordi~lg
to the invention can be applied to all dry and moist
provisions and stored goods which are susceptible to
microorganisms, such as yeasts, bacteria and especially
mould fungi.
A preferred process for applying the active substance
comprises spraying or wetting the substrate with a liquid
preparation, or mixing the substrate with a solid
preparation of the active substance. The described
conservation process forms a part of the present invention.
Active substances oE the formula I are customarily
used in the form of compositions, and can be applied,
simultaneously or successively, with further active
substances to the area or plants to be treated. These
further active substances can be fertilisers, trace-
element agents or other preparations influencing plant
growth. They can however also be selective herbicides,
insecticides, fungicides, bactericides, nematicides or
molluscicides, or mixtures of several of these prep-
arations~ optionally together with carriers commonly
~J
- 12 -
used in formulation practice, tensides or other
additives facilitating application.
Suitable carriers and additives can be solid or liquid
and they correspond to the substances customarily employed
in formulation practice, for example: natural or regenerated
mineral substances, solvents, dispersing agents, wetting
agents, adhesives, thickeners, binders or fertilisers.
A preferred method of applying an active substance
of the formula I, or an agrocllemical composition
containing at least one of these active substances,
is application to the foliage (leaf application). The
number of applications and the amounts applied are
governed by the e~tent of infesta~ion wlth respect to
the pathogen (Eun~us ~enus) concerrled. The active
substances oE the formula I can however be fed into the
plant through the soil and then by way of the root system
(systemic action), this being achieved by the locus of the
plant being soaked with a liquid preparation, or by the
substances being introduced in solid form into the soil,
for example in the form of a granulate (soil application).
The compounds of the formula I can also be applied to the
seed grains (coating), the grains being for this purpose
either soaked with a liquid preparation of the active
substance or coated with a solid preparation. Further
forms of application are possible in special cases, for
example the specific treatment of the stalks or buds
of the plants.
TLIe compounds of the formula I are used either in an
unmodified form or preferably together with auxiliaries
customarily employed in formulation practice, and are
thus processed, in a known manner, for example into the form
of emulsion concentrates, brushable pastes, directly
- J
1~568~i~
- 13 -
sprayable or dilutable solutions, diluted emulsions,
wettable powders, soluble powders, dusts or granulates,
and also encapsulations in for example polymeric sub-
stances. The application processes, such as spraying,
atomising, dust~^ng, scattering, brushing or pouring,
and likewise the type of composition, are selected to
suit the objectives to be achieved and the given conditions.
Favourable applied amounts are in general between 50 g
and 5 kg of active substance (AS) per hectare, preferably
between 10~ g and 2 kg of AS per hectare, and in particular
between 200 g and 60o g of AS per hectare.
The formulations, that is to say, the compositions
or prepara~ions containing the active substance of the
formula I and optionally a solid or liquid addi.tive, are
produced in a known manner, for example by the intimate
mixing and/or grinding of the active ingredient with
extendersg such as with solvents, solid carriers and
optionally surface-active compounds (tensides).
Suitable solvents are: aromatic hydrocarbons, prefer-
ably the fractions C8 to C12 J such as xylene mix~ures or
substituted naphthalenes, phthalic esters, such as dibutyl-
or dioctylphthalate~ aliphatic hydrocarbons, such as
cyclohexane or paraffins, alcohols and glycols, as well as
ethers and esters thereof, such as ethanol, ethylene glycol,
ethylene glycol monomethyl or -ethyl ethers, ketones
such as cyclohexanone, strongly polar solvents, such
as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethyl-
formamide, as well as optionally epoxidised vegetable
oils, such as epoxidised coconut oil or soybean oil;
or water.
The solid carriers used, for example for dusts and
dispersi.ble powders, are as a rule natural mineral fillers,
1~68
- 14 -
such as calcite, talcum, kaolin, montmorillonite or
attapulgite. In order to improve the physical properties,
it is possi~le to also add highly dispersed silicic acid or
highly dispersed absorbent polymers. Suitable granulated
adsorptive carriers are porous types, for example pumice,
ground brick, sepiolite or bentonite; and suitable
nonsorbent carriers are materials such as calcite or sand.
There can also be used a great number of pre-granulated
materials of inorganic or organic nature, such as in
particular dolomite or ground plant residues.
Particularly advantageous additives facilitating
application and rendering possible a marked reduct~.on in
the amount of active substance applied are moreover
na~ural ~anim~l o~ ve~c~able) or synthe~ic phospholipldes
~rom the class comprising the cephalins and lecithins,
for example phosphatidylethanolamine, phosphatidylserine,
phosphatidyl glycerol, lysolecithin, plasmalogenes or
cardiolipin, which can be obtained for example from animal
or plant cells, especially from the brain, heart, liver,
egg yokes or soya beans. Applicable commercial mixtures
are for example phosphatidylcholine mixtures. Synthetic
phospholipides are for example dioctanoylphosphatidyl-
choline and dipalmitoylphosphatidylcholine.
Depending on the nature of the active ingredient of
the formula I to be formulated, suitable surace-active
compounds are nonionic, cationic and/or anionic tensides
having good emulsifying, dispersing and wetting properties.
By 'tensides' are also meant mixtures of tensides.
Suitable anionic tensides are both so-called water-
soluble soaps as well as water-soluble, synthetic,
surface-active compounds.
::L2~S~9
- 15 -
Soaps ~hich are applicable are for example the alkali
metal, alkaline-earth metal or optionally substituted
ammonium salts of higher fatty acids (C10 C22), for example
the Na or K salts of oleic or stearic acid, or of natural
fatty acid mixtures, which can be obtained for example from
coconut oil or tallow oil. Also to be mentioned are the
fatty acid-methyl-taurine salts.
So-called synthetic tensides are however more
frequently used, particularly fatty sulfonates, fatty
sulfates, sulfonated benzimidazole derivatives or
alkylarylsulfonates. The fatty sulfonates or sulfates
are as a rule in the ~orm oE alkali metal, alkali.ne-earth
metal or optionally substituted ammonium salts, and
contaill an alkyl group havin~ ~ to 22 C atoms, 'allcyl'
including also the alkyl moiety o acyl groups, for
example the Na or Ca salt of ligninsulfonic acid, of
dodecylsulfuric acid ester or of a fatty alcohol sulfate
mixture produced from natural fatty acids. Included among
these are also the salts of sulfuric acid esters and
sulfonic acids of fatty alcohol ethylene oxide adducts.
The sulfonated benzimidazole derivatives preferably contain
2 sulfonic acid groups and a fatty acid group having
8 - 22 C atoms. Alkylarylsulfonates are for example the
Na, Ca or triethanolamine salts oE dodecylbenzenesulonic
acid, of dibutylnaphthalenesulfonic acid or of a
naphthalenesulfonic acid-formaldehyde condensation product.
Also suitable are corresponding phosphates, for example
salts of the phosphoric ester of a p-nonylphenol-~4-14)-
ethylene oxide adduct.
Suitable nonionic tensides are in particular polyglycol
ether derivatives of aliphatic or cycloaliphatic alcohols,
saturated or unsaturated fatty acids and alkylphenols,
~56
- 16 -
which can contain 3 to 30 glycol ether groups and 8 to 20
carbon atoms in the (aliphatic) hydrocarbon radical and
6 to 18 carbon atoms in the alkyl moiety of the alkyl-
phenols.
Further suitable nonionic tensides are the water-
soluble polyethylene oxide adducts, which contain 20 to
250 ethylene glycol ether groups and 10 to 100 propylene
glycol ether groups, with polypropylene glycol, ethylene-
diaminopolypropylene glycol and alkylpolypropylene glycol
having 1 to 10 carbon atoms in the alkyl chain. ~he
compounds mentioned usually contain 1 to 5 ethylene
glycol units per propylene glycol unit. Examples o~
nonionic tcnsides which may be men~loned are: nonylpheno.L-
polyethoxy~thanols, cas~or oil poLy~lycol c~Llers,
polypropylene/polyethyleneoxy adducts, tributylphenoxy-
polyethoxyethanol, polyethylene glycol and octylphenoxy-
polyethoxyethanol. Suitable also are fatty acid esters
of polyoxyethylenesorbitan, such as polyoxyethylene-
sorbitan-trioleate.
In the case of the cationic tensides, they are in
particular quaternary ammonium salts which contain as
N-substituents at least one alkyl group having 8 to 22
carbon atoms and, as further substituents, lower,
optionally halogenated alkyl, benzyl or lower hydroxyalkyl
groups. The salts are preferably in the form of halides,
methyl sulfates or ethyl sulfates, for example stearyl-
trimethylammonium chloride or benzyldi(2-chloroethyl)-
ethylammonium bromide. In the storage sector,
the additives which are preferred are those
that are safe or human and animal ~oods tu~fs .
The tensides customarily used in formulation practice
125~i8~3
-17- 21489-6852E
are described, inter alia, in the following publications:
"Mc Cutcheon's Detergents and ~mulsifiers Annual"
MC Publishing Corp., Ridgewood, New Jersey, 1981; and
Dr. Helmut Stache "Tensid-Taschenbuch" (Tenside
Handbook)~
Carl Hanser Verlag, Munich/Vienna, 1981.
The agrochemical preparations contain as a rule 0.1 to
99%, particularly of 0.1 to 95%, of active ingredient of the
formula I, 99.9 to 1%, especially 99.8 to 5%, of a solid or liquid
additive, and 0 to 25%, in particular 0.1 to 25%, of a tenside.
Whereas commercial produats are preferably in the form
of concentrated compositlons, khe preparations employed by the
end-user are as a rule diluted.
The compositions can contain further additives, such as
stabilisers, antifoaming agents, viscosi~y regulators, binders and
adhesives, as well as fertilisers or other active ingredients for
obtaining special effects.
Agrochemical compositions of the types described herein
likewise form part of the present inventlon.
The invention of this divislonal application and of the
parent application are illustrated by the following non-limitlng
Examples.
_ ~J
1256869
- 18 -
Production Examples
Example 1:
Production of 1-(2',3'-dichlorophenyl)-2-nitroethylene
~1 ,Cl
Cl ~ Cl
! '! ~ CH3-NO2 ~ ! '!
~ CHO ~ CH2CH-NO2
28.0 g of 2,3-dichlorobenzaldehyde, 13.9 g of ammonium
acetate, 13.9 ml o n.itromethane and 120 ml oE glacial
acetic acid are re~luxed for 2 hours. ~ter coollng, thc
rcaction mixturc :Ls poured on~o ice alld s~irrcd ~or 30
minutes. The ormed preclpitate is then filtered o.Ef,
washed with water and dried in vacuo.to thus obtain the
product in the form of slightly yellowish crystals,
m.p. 89 - 91C. IR (CHC13) in cm 1 1650 (C=C); 1530 and
1350 (N02). NMR (CDC13) in ppm: 7.2-7.7 (m, 4H);
8.50 (d,J= 15 Hz, lH).
Example 2: Production of l-dimethylamino-2-cyano-3-(2',3'-
dichlorophenyl)-5-nitro-but-1-ene
,Cl ~1
~ Cl CH3 ~ Cl
! I 11 ~ NC-CH=CH- ~ -t t il
j ~-/ \cH=cH-No2 \CH3 ~ H-~CH- ~
I . H2-NO2 CH3
A solution of 109 g of 1-(2',3'-dichlorophenyl)-2-
nitroethylene, 49 g of 1-cyano-2-dimethylamino-ethylene
and 1.0 litre of abs. toluene are refluxed for 50 hours.
After the reaction mixture has cooled, the toluene is
12S68
- 19 -
evaporated off and the residue obtained is stirred up
with diethyl ether. The precipitate is subsequently
filtered off, and afterwards washed with a small amount
of diethyl ether to thus obtain the product in the form of
beige-coloured crystals, m.p. 114-115C. IR (CHC13) in cm 1
2180 (CN), 1635 (C=C), 1555 (N02). NMR (CDC13) in ppm:
3.08 (s, 6H); h.6-5.0 (ABX, 3H); 6.60 (s, lH); 7.2-7.45
(ABX, 3H).
xample 3: Production of l-morpholino-2~cyano-3-(2',3'-
dichlorophenyl)-4-nitro-but-1-ene
~1 ' .
Cl ~ NC-C~I~CII-N/ /0
Cll~cll-NO2
~1
~-\ /Cl
~,/ \8H_~ - cH - ~ /
,I Hz-NOz --
5.0 g of 1-(2',3'-dichlorophenyl)-2-nitroethylene,
3.18 g of 3-morpholinoacrylonitrile and 30 ml of
tetrahydrofuran (abs.) are refluxed for 24 hours, and the
reaction solution is subsequently concentrated by evapor-
ation. The resulting residue, dissolved in toluene/ethyl
acetate (2:1 V/V), is chromatographed through silica g$1,
and from the eluate is thus obtained the finished product,
m.p. 74-77C. IR (CHC13) in cm 1; 2200 (CN), 1630 (C=C),
1560 (N02). NMR (CDC13) in ppm: 4.5 (m, 4H); 4.7 (m, 4H);
4.8 (ABX, 3H); 6.60 (s, lH); 7.2-7.5 (m, 3H).
56!369
- 20 -
Example 4: Production oE 3-cyano-4-(2',3'-dichlorophenyl)-
pyrroline
a) '~ \ ~Cl ~\ /Cl
!~ I) ÇN CH3 H2 1 /11~ ~N CH3
ÇH -~= CH~ H-~CH- ~
~H2-NO2 CH3 ~Hz-N~l2 \CH3
. (~1
b) cyclisation j ~-~ /Cl
~ \ /CN
!,~'!
a) 6.28 g o~ 1-cllme~hylarnlno-2-cyano-3-(2',3'-dlcllloro-
phenyl)-4-nitrobut-1-ene are hyclrogenated in 100 ml oE
ethyl acetate at 35C and under 4 bar, in the presence of
1.2 g of a platinum/active charcoal catalyst (5%) until
the absorption of hydrogen has ceased (= 1313 ml o~ H2,
corresponding to 98% of theory). The mixture is subsequently
filtered off from the catalyst, and the solution obtained
is concentrated by evaporation.
b~ The residue of (a) is taken up in 45 ml of glacial acetic
acid, and the solution is stirred at 50C for 1 hour; it
is subsequently concentrated by evaporation, and the
residue is distributed between ethyl acetate and water; the
organic phase is dried over MgS04 and then concentrated by
evaporation. The residue obtained slowly crystallises
and is treated with diethyl ether. The resulting product
is in the form of a white powder, m.p. 150-151C.
IR (CHC13) in cm : 3450 (NH), 2200 (CN), 1605 (C=C~.
NMR (CDC13) in ppm: 3.4 (dxq, lH); 4.2 (m, 2H, of which ¢lH is
replaceable by means of D20); 4.8 ~q, lH); 7.2-7.4 (m, 4H). MG: 238.
- 21 -
Example 5-
.
Production of 3-cyano-4-(2',3'-dichlorophenyl)_ ~ 2 pyrroline
.~ \i/ C}13 H2 ~ Cl
~H2-NO2 N~CH3 ) !.~ ,'!, ~CN
31.4 g of 1-dimethylamino-2-cyano-3-t2',3'-dichloro-
phenyl)--4-nitrobut~l-ene are hyclrogenated in ~00 ml o~
diox~nc a~ 100C and 100 ~r i.nL~i~l pressure o~ hyclro~n,
in the presencc oE 6.2 g o~ cobal~ polysulfide, for 7 1/2
hours. After this period o~ time, the measurement at room
temperature indicates a hydrogen absorption of 6.39 litres
of H2 (corresponding to 95% of theory). The mixture is
subsequently filtered; the catalyst is washed with dioxane
and the filtrate is concentrated by evaporation. The
residue is chromatographed with toluene/ethyl acetate (2:1)
through silica gel to thus obtain the product in the form
of a white powder, m.p. 150C. IR (CHC13) in cm 1
3450 (NH), 2200 (CN), 1605 (C=C). NMR (CDC13) in ppm:
3.4 (dxq, lH); 4.2 (m, 2H, Of which lH is replaceable by means
of D20); 4.8 (q, lH); 7.2-7.4 (m, 4H). MG: 238.
Example 6:
Production of 3-cyano-4-(2',3'-dichlorophenyl)-pyrrole
Cl oxidation ~-~ /Cl
CN ~ /CN
!~i! il~!i
~L25~8~9
- 22 -
a) 1.0 g of 3-cyano-4-(2',3'-dichlorophenyl~-~2-pyrroline
is dissolved in 15 ml of CHC13, and to the solution is
added 0.67 g of bromine. After 15 minutes, no further
educt is detectable by thin-layer chromatography. 1.4 ml
of triethylamine are added to the reaction solution, and
stirring is maintained for 1 hour at 40Co The reaction
mixture is subsequently washed with water; the organic
phase is then dried over MgS04 and concentrated by
evaporation. The residue dissolved in toluene/ethyl
acetate (4:1 V/V) is chromatographed through silica gel,
and from the eluate is obtained the finished product,
m.p. 1~8-150C.
b) 5.2 g o;E 3-cyallo-~-(2~3~-diclllorophenyl)-~2~pyrroli.n~
are stirred in lO0 m~ of mesil:ylene~ in the presence of
0.5 g o a palladium/active charcoal catalyst, for 14
hours at 180-200C. The catalyst is subsequently filtered
off and the filtrate is concentrated by evaporation. The
residue dissolved in toluene/ethyl acetate (4:1 V/V) is
chromatographed through silica gel, and from the eluate
is obtained the finished product, m.p. 149-151C.
c) 0.5 g of 3-cyano-4-(2',3'-dichlorophenyl)-~2-pyrroline
is stirred with 1.0 g of FeC13 in a mixture of 12 ml of
water/ethanol (3:1) for 24 hours at room temperature with
the introduction of air. The reaction mixture is poured
into water and extracted three times with 10 ml of ethyl
acetate each time. The organic phase is washed with water,
dried over MgS04 and concentrated by evaporation. The
residue is crystallised by trituration with diethyl ether,
and the resulting product is in the form of beige-coloured
crystals, m.p. 150-151C.
It is shown by the individual reaction steps of the
production process according to the invention that the
~ 2 ~ 6
- 23 -
substituent Rn in the phenyl nucleus has negligible
effect on the course of the reaction. There can be
produced in the same manner ~or example also the following
compounds, which can be used as fungicides:
-3-cyano-4-~2-chlorophenyl)-~ 2-pyrroline,
-3-cyano-4-(2,5-dichlorophenyl)-~ -pyrroline,
-3-cyano-4-(2-trifluorophenyl)- ~2_pyrroline,
-3-cyano-4-(2-bromophenyl~- ~ 2-pyrroline,
-3-cyano-4-(3-bromophenyl)- ~2-pyrroline,
-3-cyano-4-(3-fluorophenyl)- ~2-pyrroline,
-3-cynno-4-(3-tolyl)- ~2-pyrroline,
-3-cyano-~-(4-chl.oropLlenyl)-~ 2-pyrroline,
-3-cyano-4-(3-chlorophenyl)-~ 2-pyrroline,
-3 cyano-4-(4-bromophenyl)- ~ -pyrroline,
-3-cyano-4-(4-fluorophenyl)- ~ 2-pyrroline,
-3-cyano-4-(4-tolyl)-~ 2-pyrroline, and
-3-cyano-4-(2,4-diclllorophenyl)- ~ 2-pyrroline.
There can be produced by oxidation irom such compounds
of the formula I corresponding pyrrole derivatives of the
formula VII.
Formulation Examples for active ingredients of the formula I
(% = per cent by wei~ht)
1. Emulsion concentrates a) b) c)
.
active ingredient from Examples 4/5 25% 40% 50%
or from the preceding Table
calcium dodecylbenzenesulfonate 5% 8% 6%
: castor oil-polyethylene glycol 5%
ether (36 mols of e~hylene oxide)
- ~256~3~9
- 24 ~ a) b) c)
tributylphenyl-polyethylene glycol - 12% 4%
ether (30 mols of ethylene oxide)
cyclohexanone - 15% 20%
xylene mixture 65% 25% 20%
Emulsions of any required concentration can be produced
from concentrates of this type by dilution with water.
2. Solutions a) b) c) d)
active ingredient from Examples 4/5 80%10% 5% 95%
or from the preceding Table
ethylene glycol-monomethyl ether 20% - - -
polyethylene glycol (M.W. 400) - 70%
N-methyl-2-pyrrolidone - 20%
epoxidised coconut ol~ /o 5%
ligroln (boilin~ l~ml~s :160-190UC~ - - 9~%
(M.W. = molecular weight)
The solutions are suitable for application in the form
of very fine drops.
3. Granulates a) b)
active ingredient from Examples 4/5 5% 10%
or from the preceding Table
kaolin 94%
highly dispersed silicic acid 1%
attapulgite - 90V/o
The active ingredient is dissolved in methylene
chloride, the solution is sprayed onto the carrier, and
the solvent is subsequently evaporated off in vacuo.
4. Dusts a) b)
active ingredient from Examples 4/5 2% 5%
or from the preceding ~able
highly dispersed silicic acid 1% 5~/~
talcum 97%
kaolin - 90%
6~6~ ~
- 25 -
Ready-for-use dusts are obtained by the intimate
mixing together of the carriers with the active ingredient.
5. Wettable powders a) b) c)
active ingredient from Examples 4/5 25% 50% 75%
or from the preceding Table
sodium lignin sulfonate 5% 5%
sodium lauryl sulfate 3% ~ 5%
sodium diisobutylnaphthalene sulfonate - 6% 10%
octylphenolpolyethylene glycol ether -2%
(7-8 mols of ethylene oxide)
highly dispersed silicic acid 5% 10% 10%
kaolin 62% 27%
The active ingredient is well mixed with the additi.ves,
and the mixture is ~horoughly ground in a suitable m:ill.
Wettable powclers whicll can be dilu~ed with water to g:lve
suspensLons o~ the requlred concen~ratLon are obt.lined.
6. Emulsion concentrate
-
active ingredient from Examples ~/5 10%
or from the preceding Table
octylphenol polyethylene glycol ether 3%
(4-5 mols of ethylene oxide)
calcium dodecylbenzenesulfonate 3%
castor oil polyglycol ether 4V/o
(3S mols of ethylene oxide)
cyclohexanone 30%
xylene mixture 50%
Emulsions of the required concentration can be obtained
from this concentrate by dilution with water.
7. Dusts a) b)
.
active ingredient from Examples 4/5 5% ~%
or from the preceding Table
talcum 95%
kaolin - 92%
- 26 -
Dusts ready for use are obtained by mixing the active
ingredient with the carriers and grinding the mixture
in a suitable mill.
8. Extruder ~ranulate
active ingredient from Examples 4/5 10%
or from the preceding Table
sodium lignin sulfonate 2%
carboxymethylcellulose 1%
kaolin 87%
The active ingredient is mixed and ground with the
additives, and the mixture is moistened with water. This
mixture is extruded and subsequently dried in a stream
of air.
9. Coated ~ranulate
active ingredient ~rom I~xamples 4/5 3%
or from the precediny Table
polyethylene glycol (M.W. 200) 3%
kaolin 94%
(M.W. = molecular weight)
The finely ground active ingredient is evenly applied
in a mixer to the kaolin moistened with polyethylene
glycol. Dustfree coated granules are obtained in this
manner.
10. Suspension concentrate
active ingredient from Examples 4/5 40%
or from t~e preceding Table
ethylene glycol 10%
nonylphenolpolyethylene glycol ether 6%
(15 mols of ethylene oxide)
sodium lignin sulfonate 10%
carboxymethylcellulose 1%
37% aqueous formaldehyde solution 0.2%
- y
6869
- 27 -
silicone oil in the form of a 0.8%
75% aqueous emulsion
water 32%
The finely ground active ingredient is intimately
mixed with the additives. There is thus obtained a
suspension concentrate from which can be produced, by
dilution with water, suspensions of the concentration
required.
Biolo~ical Examples
Example 1: Action azainst Botrytis cinerea on bean plants
Residua:l-protective action
Bean plan~s a~out lO cm Ln hel~h~ are sprayed wlt~l
a spray liquor preparecl ~rom wet~able powder of the actlve
ingredient (0.002% oE active ingredient). The plants are
infested after 48 hours with a conidiospore suspension oE
the fungus. The extent of fungus in~ection is assessed
after incubation of the infested plants for 3 days at
21C with 95-100% relative humidity.
The compounds from the Tables greatly reduce fungus
infection not only in the above model test but also in
the field test. At a concentration of 0.002%, the compound
of Examples 4/5 for example proves fully effec-tive ~infection
O to 5%). Infection on infested but untreated bean plants
is however 100%.
Example 2: Action a~ainst Botrytis cinerea on apples
Artificially damaged apples are treated by applying
drops of spray liquor, prepared from wettable powder of
the active ingredient (0.002% of active ingredient), to the
damaged areas on the apples. The treated fruit is then
inoculated with a spore suspension of Botrytis cinerea,
~ 6
- 28 -
and is incubated for one week at about 20C with high
relative humidity.
For an assessment of the results, the decayed areas
of damage are counted, and from the number is deduced
the fungicidal action of the test substance. Amongst
other effective compounds, the compound of Examples 4/5
completely prevents fungus infection, whereas the level of
infection on untreated control fruit is lO0~.