Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
~ V 516734
The present invention relates to new and valuable
morpholine derivatives and their salts and molecular compounds
and adducts, having a good fungicidal actionl Eungicides
containing these compounds, and processes for combatting
fungi with these compounds.
The use of N-tridecyl-2,6-dimethylmorpholine and
its salts, molecular compounds and adducts as fungicides has
been disclosed (German 1,164,152, German 1,173,722, German -
Laid-Open Application DOS 2,461,513).
We have now found that morpholine derivatives of the ~ :
formula R3 Rl
CH -C ~ CH2-CH-CH2-N O
R2 :.
where Rl, R2, R3 and R4 denote hydrogen, methyl or ethyl, and
their salts, moleeular compounds and~adduets have a good
fungieidal aetion which is superior to the aetion o prior art
morpholine derivatives.
~ Examples of salts are those wi~th inorganic or organic
aeids, e.g., ehlorides, fluorides, bromides, iodides, sulfates,
nitrates, phosphates, aeetates, propionates~and fumarates.
Moleeular eompounds and adduc~ts are formed for i-nstanee with
aeids o~f surfaetants, e.g., dodecylbenzenesulfonie acid.
.. . .. ,, ': .
I~ the~new~eompounds are 2,6-dimethyl derivatives, they
may ~e isolated as Ci6 and trans isomers.
The morpholine derivatives of the invention are
. .
prepared by reaeting 3-p-tert-butylphenyl-2-methylpropanal of
the formula~
~ CH3 CH3 ~ O
~ ~ ; CH3-C ~ CH2-CH-C
CH3 ~ H
:: : ; - 1 - .::
`: :,'
734
is reacted with a morpholine of the Eormula
R Rl
~/
H - N b
R2 ~ R4
whère Rl, R , R3 and R4 have the above meanings, in ~he presence
of formic acid, with or without a diIuent, at temperatures of
from 50 to 110C.
The preparation of the new compounds is illustrated
by the following examples. ~-~
EXAMPLE 1
Synthesis of N-(3-p-tert-butylphenvl-2-methyl-1-propyl)-cis-
2,6-dimethvlmorpholine
~ , .
2,6-Dimethylmorpholine which has been obtained by
suIfuric acid-catalyzed cyclization of diisopropanolamine is
separated into the cis and trans forms by fractlonal
distillation in a column packed with steel mesh coils. About
75 wt% of~the 2,6-dimethylmorpholine is in the cis
configuration, the remainder in the trans form. The isomers are
separated by fractional distillatlon i.n a column having about 40
theoretical plates. The cis form dis~ils as a 99~ product at
80 to 81C and a pressure of 100 mm Hg. ~The trans-form of
2,6-dimethylmorpholine may be obtained under the same
conditions at 88 to 89C/100 mm Hg as~ a more than 95~ product.
575 g of 98% formic acid is placed in a stirred
apparatu8 equipped with reflux condenser, thermometer and dropping
funnel.~ While stirring and cooling 345 g of 99% 2,6-cis-
; dimethylmorpholine is then dripped in. ~he~mix*ure issubsequently slowly heated on a water bath to 70C. Over a
~period of~4~ho~urs,~ 612 g of 3-p-tert-butylphenyl-2-methylpropanal
30~ ~ is dripped lnto the reaction mixture, a temperature of approx. -
100C being~maintained. Condensation proceeds with marked
;~evolu~tion of~CO2. Upon conclusion of the reactlon the mixture
: : L~ :: : 2 -
.~. .~,.: :. : . :
: . . . .
6734
.
is kep~ for 2 hours at 100C while s~irriny.
.
The excess formic acid is then d.istilled o~f undex
reduced pressure. Substantial separation of the formic acid
~is achieved under a water pump vacuum at 100C.
'
. . .
: .
.
' ~ . : ' ~ ' .,
' ' ' ' ' "'
:-.
.
. ~ ~ '.,'; "' ' "
:
,. ~ ~ : ~ - . . ' ' -,: '
:
, :. : : . ,
:, : .: ~ ' ' .
:
' ' ~ ~ ' , ,,, :.
.
, . : .. ' ' :.:
2à -
-- .
~lO~ Ei734
~ O.Z. 32,325
The base is liberated from the formate by dripping in 500 g
o~ 40% aqueous caustic soda solutionO The caustic soda solution
is advantageously added at from 80 to 100C to facilitate ad-
mixture of the amine phase which forms with the caustic phase.
200 g of toluene is added to depress the viscosity. After
separation of the caustic phase, the organic phase is washed twice
with water, each time with 250 g.
For further purification, the amine is fractionally distil-
led at 0. 2 mm Hg in a distillation column having 5 trays. In
addition to a small amount of first runnings (up to 143C/0.2 mm Hg;
50 g), there is obtained 865 g of N-(3~tert-bu~ylphenyl)-2-methyl
1-propyl)-2~6-cis-dimethylmorpholineg which distils at 0.2 mm Hg
between 14~ and 146C. According to gas-chromatographic analysis~
the amine is more than 98% pure. With reference to aldehyde~ the
yield was 84.5%.
To convert the compound to the hydrochloride, 30 g of the
pure product is dissolved in 50 g of ethanol which has been
saturated with hydrogen chloride at room temperatureO After cooling,
there is obtained 23 g of the hydrochloride (m.p. 220C) in very
pure form.
EXAMPLE 2
Synthesis of N-(3-p-tert-butylphenyl-2-methyl-1-propyl )-?~-
trans-dimethylmorpholine
While cooling with ice, 29 g o~ 2,6-trans-dimethylmorpholine
is introduced into 70 g of 98% formic acîd, While stirring, 41 g
o~ 3-p-tert-butylphenyl-2-methylpropanal is then added. The
reaction mixture is heated for 6 hours at 100C. IJpon commencement
Or the reaction~ very strong C02 e~olution takes place which drops
noticeably a~er about an hour. Further working up is effected
:
as disclosed in more~detail in Example 1,
3 N-(3-p-tert-butylphenyl-2-methyl-1-propyl)-2,6-trans-di-
methylmorpholine dist~lls at 168-169C (5 mm Hg). The yield is
~ 3~
~ 734 o.z. 32,325
52 g (86% of theory, with reference to aldehyde). 11 g of the
amine is dissolved in 20 g o~ ethyl acetate which has been
saturated with anhydrous hydro~en chloride. The hydrochloride
crystallizes out upon cooling; m.p.: 165C.
The other compounds are obtained analogously.
Examples of compounds accordin~ to the invention are ~iven
below:
CH CH
3 , ~ CH2-CH-CH2-
CH3
Compound no.
1 R-N ~ b.p.: 123C/0.01 mm
2R-N ~ 0 ,H25C12 ~ m.p.: 108C
~~ ~ CH3
3 R-~ 0 ~b.p.: 143-146C/0.2 mm
\~
CH3
cis form
nT~
~ 3
4 R-~ 0 b.p.: 168-169Ci5 mm
CH3
trans form
F H3
R-N ~ .HCl m.p.: 220C
; cis ~orm
~ 3S73~
O.Z. 32,32
~ CH3
6 R-N O .HCl m.p.: 165C
CH
trans form 3
10R-N ~ b.p.: 128C/0.02 mm
I CH3
CH3
11R-N ~ b.p.: 133C/0.05 mm
3 .
CH ~
12R-N ~ ~ b.p.: 125C/0.02 mm
CH3
, . .
13 R-N~_~0 b.p.: 170C/5.0 mm
14 R-N ~ . HCl m.p.: 206C
H3C
15R-N O b.p.: 145C/0.3 mm
H3C . :
16R-N ~ O . HCl m.p.: 172C
2 5 .
17R-N ~ b.p.: 148C/0.3 mm
C2 5
~ 2 5
18R- ~ O b~p.: 146-148C~0.3 mm
2 5
~ CH3
19R-N ~ .HBr m.p.: 228C
cis ~orm
~ CH3
R-N 0 .HOOC ~ CH m.p.: 174C
~ CH3 HC COOH
cis form
_ 5 -
, - - -- - .: - - . . .. -:
~ 34 ~). z. 32,~25
The active ingredients according to the invention and the
fungicides containing them are partlcularly suitable for combatting
plant diseases such as Erysiphe ~raminis in cereals, Erysiphe
cichoriacearum in Cucurbitaceae, Podosphaera leucotricha in apples,
Uncinula necator in grapes,Erysiphe ~olygoni in beans, Sphaerotheca
annosa in roses, r~icrosphaera querci in oaks, Botrytis cinerea
in strawberries and grapes,r~ycos~haerella musicola in bananas,
Puccinia species (rusts) in cereals, IJromyces appendiculatus and
U. phaseoli in beans, Hemileia vastatrix in coffee, and Rhizoctonia
solani. They have a systemic action; they are not only taken up by
- the roots but also absorbed by the leaves, and are translocated in
the plant tissue.
Application is effected for instance by watering, spra~ing,
dusting, or disinfecting the plants or treating the seed wlth the
active ingredients.
When the new active ingredients are used to protect plants
against fungus infec~ion, the application rates are from 0.025 to
5 kg of active in~redient per hectare. For the surface protection
of trees or fruit, the active ingredients may also be used in
combinatioh with plastics dispersions in amounts of from 0.25 to
5%, based on the weight of the dispersion. In general, the fungi-
cides contain from 0.1 to 95, preferably from 0.5 to 90, wt~ of
active ingredient.
The active ingredients may also be mixed with other, prior
art, fungicides. In many instances, the spectrum of fungicidal
action is increased; with a number of fungicidal compositions in
the weight ratio range of 1:10 to 10:1 synergistic effects also
occur, i.e.~ the fungicidal action of the combination product is
greater than the effect of the individual components added together.
Exam~les Or fungicides which may be combined with the compounds
of the invention are
dithiocarbamates and derivatives thereof, e.g1,
zinc dimethyldithiocarbamate
~''.
- 6 -
4 o.z. 32,325
manganese ethyleneb isdithiocarbamat
zinc ethylenebisdithiocarbamate
tetramethylthiuram disul~ide
ammonia co iex o~ zinc-(N,N'-ethylene-bisdithiocarbamate)
and
N,N'-polyethylene-bis-(thiocarbamoyl)-disul~ide
ammonia complex of zinc-(N,N'-propylene-bisdithiocarbamate)
and
N,N'-polypropylene-bis-(thiocarbamoyl)-disulfide
heterocyclic structures, such as
N-trichloromethylthiotetrahydrophthalimide
N-trichloromethylthiophthalimide
N-(1,1,2,2-tetrachloroethylthio)-tetrahydrophthalimide
methyl 1-(butylcarbamoyl)-2-benzimidazole carbamate
2-methoxycarbonylaminobenzImidazole . .
2,3-dihydro-5-carboxanilido-6-methyl-1~4-oxathiin-~,4-dioxide
2~3-dihydro-5-carboxanilido-6-methyl-194-oxathiin
5-butyl-2-dimethylamino-4-hydroxy-6-methylpyrimidine
1~2-bis-(3-ethoxycarbonyl-2-thioureido)-benzene
1,2-Ois-~3-methoxycarbonyl)-2-thioureido)-benzene
and various fungicides, such as
dodecylguanidine aoetate
N-dichlorofluoromethylthio-N'9N'-dimethyl-N-phenylsulfuric acid
diamide
2,5-dimethylfuran-3-carboxylic acid anilide
2,5-dimethylfuran-3-carboxylic acid cyclohexyl amide
2-iodobenzoic acid anilide
2-bromobenzoic acid anilide
3-nitroisophthalic acid diisopropyl ester
30 ~ 1,2~4-triazolyl-1') Ll- ( 4'-chloropheno~y)]-3,3-dimethyl-
butan-2-one
imidazolyl)-2-allylo~J-2-(2,4-dichlorophenyl)-ethane
.
~ ~ ~ ~ 7 ~ ~ -
6,734
O.Z. 32,325
piperazine-1,4-diyl-bis-1-(2,2,2-trichloroethyl)-formamide
2~4,5,6-tetrachloroisophthalonitrile
1,2-dimethyl-3,5-diphenylpyrazoliniummethylsulfate.
Application may be effected for instance in the form of
directly sprayable solutions, powders, suspensions, dispersions,
emulsions, oil dispersionsS pastes, dusts, broadcasting agents, or
granules by spraying~atomizing, dusting, broadcasting or ~atering.
The rorms o~ application depend entirely on the purpose for which
the agents are being used; in any case they should ensure a fine
distribution of the active ingredient.
For the preparation of solutions, emulsions, pastes and
oil dispersions to be sprayed direct, mineral oil fractions of
medium to high boiling point, such as kerosene or diesel oil,
further coal-tar oils, etc. and oils of vegetable or animal
origin, aliphatic, oyclic and aromatic hydrocarbons such as
benzene, toluene, xylene, paraffin, tetrahydronaphthalene, alkyl-
ated naphthalenes and their derivatives such as methanol, ethanol,
propanol, butanol, chloroform, carbon tetrachloride, cyclohexanol,
cyclohexanone, chlorobenzene, isophorone, etc., and strongly polar
solvents such as dimethylformamide, dimethyl sulfoxide, N-methyl-
pyrrolidone, water, etc. are suitable.
A~ueous formulations may be prepared from emulsion con-
centrates, pastes, oil dispersions or wettable powders by adding
water. To prepare emulsions, past s and oil dispersions the
in~redients as sUch or dissolved in an oil or solvent may be
homo~enized in water by means of wetting or dispersing agents,
adherents or emulsifiers. Concentrates which are suitable ~or
dilution with water may be prepared from active ingredient,
wetting;agent, adherent, emulsifying~or dispersing agent and -~
possib~ly 901vent or oil. -
- 8 -
. .
:
~cF3~ 7 3 4
^ O.Z. 32,325
~xamples of surfactants are: allcali metal, alkaline earth
metal and ammonium salts Or ligninsulfonic acid, naphthalene-
sulfonic acids, phenolsulfonic acids~ alkylaryl sulfonates,
alkyl sulfates, and alkyl sulfonates3 alkali metal and alkaline
earth metal sal~s of dibutylnaphthalenesulfonic acid, lauryl
ether sulfate, fatty alcohol sulfates, alkali metal and alkaline
earth metal salts of ~atty acids, salts of sulfated hexadecanols,
heptadecanols, and octadecanols, salts of sulfated fatty alcohol
glycol ethers, condensation products of sul~onated naphthalene
and naphthalene derivatives with formaldehyde, condensation pro-
ducts o~ naphthalene or naphthalenesulfonic acids with phenol
and formaldehyde, polyoxyethylene octylphenol ethers, ethoxylated
isooctylphenol, ethoxylated octylphenol and ethoxylated nonyl-
phenol, alkylphenol polyglycol ethers, tributylphenol polyglycol
ethers, alkylaryl polyester alcohols, isotridecyl alcohols, fatty
alcohol ethylene oxide condensates, ethoxylated cas~or oil, poly-
oxyethylene alkyl ethers, ethoxylated polyoxypropylene, lauryl
alcobol polyglycol ether acetalg sorbitol esters, lignin, sulfite
waste liquors and methyl cellulose.
Powders, dusts and broadcasting agents may be prepared by
mixing or grinding the active ingredients with a solid carrier.
Granules, e.g., coated, impregnated or homogeneous granules,
may be prepared by bonding the active in~redients to solid carriers.
Examples of solid carriers are mineral earths such as silicic
acid, silica gels? silicates, talc, kaolin, Attaclay, limestone,
lime, chalk, bole, loess, clay, dolomite, diatomaceous earth,
calcium sulfate, magnesium sul~ate, magnesium oxide, ~round
plastics,~fertilizers such as ammonium sulfate, ammonium phos~
phate, ammonium nitrate, and ureas, and vegetable products such as
3 grain flours, bark meal, wood meal, and nutshell meal, cellulosic
powders, etc.
~ 9
' ~ .
:::
i734
O,Z. 32,325
There may be added to the CompoSitions or individual active
ingredients oils of various types, herbicides, f~glcides, nema-
tocides, insecticides, bactericides, trace elements~ fertilizers,
antifoams (e.g., silicones), growth regulators, antidotes and
other herbicidally effective compounds.
The the following experiments, the following prior art com-
pounds were used for comparison purposes:
Compound
no.
~~~\~ CH3
7 C13H27 N ~
C~3
(prior art)
~ CH3
8 C13~27 ~ .CH3COOH
CH3
(prior art)
9 C13H2 - ~ .C12~25 ~ 3
(prior art) 3
~.
EXAMPLES 3
Leaves of what seedlings o~ the "Jubilar" variety grown in
pots are treated with aqueous emulsions consisting of 80% (wt%) of
10 active ingredient and 20% emulsifier and dusted, after the sprayed-
on layer has dried, with spores of wheat mildew (Erysi~he graminis
~ar._tritici). The plants are then placed in a greenhouse at from
20 ~o 22C and 75 to 80% relative humidity. The extent the fungus
has spread is determined after 10 days.
- 10 -
.
''" ' '
, . . . . .. . .. .. .. ..
~ 11~6734
-:` 0,Z. 32,325
Active ingredient Leaf attack after spraying with liquors con-
taining active ingredients in amounts of
0 006%0.012% 0.025% 0.05%
1 1-2 1 0-1 0
2 1 0-1 0 0
3 0 0 0 0
4 1 0 0 0 ~-
0 0 0 0 :
6 1 0 0 0 ~ .
19 0 0 0 0 '. -
0 0 0 0
7 ) 3-4 3 2
8 ) prior art 4 4 2
9 ) 2 1 1 0
Control (untreated) 4 : ;
0 = no attack~ graduated down to 5 = surface of leaves completely
covered by fungus.
~ EXAMPLE 4
:
: .
Leaves of barley seedlings of the "Firlbecks Union" variety -~
grown in pots are tre~ated as described in Example 3, and dusted with ~-
spores of barley~mildew (Erysiphe Qraminis var. hordei). ~ : .
Active ingredient~; Leaf attack after spraying with :liquors con-
taining:active ingredient in amounts of
0:.o06% ~ 0.012% 0.025%
~O: O
2 ~ 0 0 0 ~ `.
:-,
~ o O
4 . :0 0 0
0 0 O
6 ~ ~ 0 0 0 :
19 ~ ~ ~ 0 ~ ~ ~ 0 O
:~20 ~ 0~ : 0 0
~ prior~art ~ 2~ ; 1 0-1
: Control::(untreated) _ _ 4 _ :
O~ no:~ attack3 ~gràduated down to 5 - surface of leaves completely
covered~:by~ungusO ~
r 1~3~734
O.Z. 32,325
EXAMPLE 5
Leaves of wheat plants grown in pots are artificially in-
fected with spores of lea~ rust (Puccinia recondita) and placed
for 48 hours in a steam-saturated chamber kept at 20 to 25C.
The plants are then sprayed with aqueous liquors containing a
mixture, dissolved or emulsified in water, of 80% o~ the active
ingredient and 20% o~ sodium lignin sulfonate, and placed in a
greenhouse at ~rom 20 to 22C and 75 to 80% relative humidity.
The extent the fungus has spread is assessed after 10 days.
Active ingredient Leaf attack after spraying with liquor con- -
taining active ingredient in amounts o~
0.025 0.05 0.1
... ... _ .
1 2-3 1-2 0
3 0 0 0
4 0 0 0
o o 0
6 0 0
19 O O O - '
7 ) 4 3 2
8 ) prior art 4 4 3
9 ) ll 3 3
Control untreated) 4
0 = no damage, graduated down to 5 = surface of leaves completely
covered by fungus.
~ ~ EXAMPLE 6
90 parts by weight of compound 3 is mixed with 10 parts by
wei~ht o~ N-methyl~-pyrrolidone. A mixture is obtained which is
.
suitable for~application~in the form of very fine drops.
EXAMPLE 7
20 parts by weight of compound 4 is dissolved in a mixture
~consisting~of 80 parts by weight of xylene, 10 parts by weight
of the~adduct of 8 to 10 moles of ethylene oxide to 1 mole o~
12 -
~: :
.. . . ..... . ..
673~
~ .Z, 32,~25
oleic acid ~-monoethanolamide, 5 parts by weight of the calcium
salt of dodecylbenzenesulfonic acid, and 5 parts by weight o~
the adduct of 40 moles o~ ethylene oxide to 1 mole of castor
oil. By pouring the solution into 100,000 parts by weight of
water and uniformly distributing it therein, an aqueous dispersion
is obtained con~aining 0. 02% by wei~ht of the active ingredient.
EXAMPLE 8
20 parts by weight o~ compound 3.is dissolved in a mixture
consisting of 40 parts by weight of cyclohexanone, 30 parts by
weight o~ isobutanol, 20 parts by weight of the adduct of 7 moles
of ethylene oxide to 1 mole of isooctylphenol, and 10 parts by
weight of the adduct of 40 moles o~ ethylene oxide to 1 mole of
castor oil. By pouring the solution into 100,000 parts by weight
of water and uniformly distributing it therein, an aqueous dis
persion is obtained containing 0002% by weight of the active
ingredient.
EXAMPLE 9
20 parts by weight of compound 4 is dissolved in a mixture
consisting o~ 25 parts by weight of cyclohexanol, 65 parts by
weight of a mineral oil fraction having a boiling point between
210 and 280C, and 10 parts by weight of the adduct of 40 moles
of ethylene oxide to 1 mole of castor oil. By pouring the solution
into 100,000 parts by weight of water and uniformly distributing
it therein, an aqueous dispersion is obtained containing .?~ by :-~
weight o~ the active ingredient. ::
EXAMPLE 10
20 parts by weight of compound 5 is well mixed with 3 parts
by weight of the sodium salt of diisobutylnaphthalene-~,-sulfonic
acid, 17 parts by weight of the sodium salt of a ligninsulfonic
acid obtained from a sulfite waste liquor~ and 60 parts by weight .:
,, .
-- 13 --
~ , .
73~
o.z. 32,325
of powdered silica gel, and triturated,in a hammer mill. By
uniformly distributing the mixture in 20,000 partS by weight of
water, a spray liauid is obtained containing 0. l~o by weight of the
active ingredient.
EXAMPLE 11
3 parts by weight of compound 3 is intimately mixed with
97 parts by weight of particulate kaolin. A dust is obtained con-
taining 3% by weight o~ the active ingredient.
~XAMPLE 12 -
30 parts by weight of compound 4 is intimately mixed wikh a
mixture consisting of 92 parts by weight of powdered silica gel
and 8 parts by weight of paraffin oil which has been sprayed onto
the surface of this silica gel. A formulation of the active
ingredient is obtained having good adherence.
EXAMPLE 13
40 parts by weight of compound 3 is intimately mixed with
~0 parts of the sodium salt of a phenolsulfonic acid-urea-formalde
hyde condensatej 2 parts of silica gel and 48 parts of water to ',
give a stable aqueous dispersion. Dilution in 100,000 parts by
weight of water ~ives an aqueous dispersion containing 0.04 wt% of
active ingredient.
EXAMPLE 14
20 parts of compound 4 is intimately mixed with 2 parts of
the calcium salt of dodecylbenzenesulfonic acid, 8 parts of a
fatty aloohol polyglycol ~ether, 2 parts of the sodium salt of a
phenolsulfonic acid-urea-~ormaldehyde condensate and 68 parts of a
paraffinic mineral oil. A stable oily dispersion is obtained. '
. .
.
..
: '
