Note: Descriptions are shown in the official language in which they were submitted.
gZ
5- 12064/MAC 1742 /=
~gent and method for influencing plant growth containing
phosphonous acid peptides
The present invention relates to a novel agent for
influencing plant growth, in particular to a herbicidal
and plant growth regulating agent, and to a process ~or
inhibiting and suppressing plant growth in monocotyledonous
and dicotyledonous plants, especially grasses, cereal
crops, soya, tobacco and ornamental plants.
According to the present invention, there is provided
an agent for influencing plant growth, in particular a herbicide
and plant growth inhibiting agent comprising, in addition
. , . : -~
.. .
, ' ' ,~' ~ ."' ,, "',
81~f~
to carriers and/or other additives, at least one compound of formula
13 ~ 2_co ~ NH~C - P - H (I)
n R OH
or the oorresponding zwitterion form in which R and Rl may be the same
or different and each can be hydrogen, deuterium or a lower alkyl group,
lower alkenyl, lower aLkynyl, C3-C7 cycloalkyl, phenyl or by a 5-membered,
nitrogen containing ring containing one or mDre oxygen, nitrogen or
sulphur atoms and which may be fused to an aromatic ring, a lower alkyl
group substituted by a C3-C7 cycloalkyl radical, a lower alkyl group
substituted by a phenyl radical, a lower alkyl group substituted by a
5 me~bered, nitrcgen oontaining ring as defined above, or R and Rl
together form a polymethylene chain optionally interrupted by an oxygen,
nitrogen or sulphur atoms, or ~ represents, together with the C(R) -N
residue to which it is attached, the atoms required to cc~plete a 5
nembered nitrogen containing ring and R2 and R3 may be the same or
different and each can be hydrogen, lower alkyl, C3-C7 cycloalkyl, phenyl
or lower alkyl substituted by a C3-C7 cycloalkyl radical, lower alkyl
substituted by a heterocyclic radical oontaining one or mDre nitrogen
atcms; a 5-membered ring containing one or more nitrogen atcms; or R2
and R3, independently, together with the C(H)-N residue to which each
is attached, may each repre æ nt the atoms required to co~plete a 5
membered nitrogen containing ring and N is 0, 1, 2, or 3; as well as the
esters and salts thereof with the physiologically ac oe ptable alcohols or
acids or ba æ s respectively and all optical isomers thereof. The ~-amino
acid residues or esters occurring in the peptides defined above may have
the P,Lr L- or D- configuration.
2 -
.
.
'` .: ~, , , ,:
. . :, .
:.
., . . . . .....
The term "lower" referred to above and hereinafter in connection
with organic radicals or compounds respectively, defines such with up
to 6, preferably up to 3 carbon atoms.
me above listed radicals R, Rl, R2 and R3 optionally may be
substibuted by one or m~re functionalgroups, as for example, free or
etherified hydroxy or mercapto groups, optionally converted carboxyl
groups, S-substituted dithio groups, optionally substituted amino groups
iNR4R5- in which R4 and R5 may be the same or different and can be hydrogen
or lower aIkyl or optionally substituted guanidino and~or
: :: . , ,
. . ...
8~Z
option~lly substituted aryl groups or heterocyclic residues.
~ loreover R and Rl as lower alkyl group, aryl group
or heterocyclic radical or an aryl group or heterocyclic radical
as substituent of R or Rl as lower alkyl group may be substituted
by one or more halogen atoms, -NR4R5 groups in which R4 and R5
together form a polymethylene chain containing up to 6 carbon
atoms which may optionally be interrupted by oxygen or nitrogen
or an aryloxy group optionally substituted by hydroxy or an
halogen atom as for example iodine.
The substituénts ~, Rl, R2 and R3 as lower alkyl group
may be a straight or branched chain alkyl group of 1 to 6 carbon
atoms and may be for example, methyl, ethyl, n-propyl, iso-
propyl, n-butyl, isobutyl, secondary butyl, tertiary butyl,
n-amyl, isoamyl or n-hex~l. Preferred are lower alkyl groups
of 1 to 3 carbon atoms as for example methyl, ethyl, n-propyl
or isopropyl.
When R, Rl, R2 or R3 is a cycloalkvl group this may
be a cycloalkyl group with 3 to 7 carbon atoms as for example
a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclo-
heptyl group.
LS~
-5-
A lower alkyl group substituted by a cycloalkyl
radical may be for example cyclopropyl-methyl, cyclopropyl-ethyl,l
cyclopropyl-n-propyl, cyclobutyl-methyl, cyclobutyl-ethyl, ~.
cyclobutyl-n-p~opyl, cyclopentyl-methyl, cyclopentyl-ethyl,
cyclopentyl-n-propyl, cyclohexyl-methyl, cyclohexyl-ethyl,
cyclohexyl-n-propyl, cycloheptyl-methyl, cycloheptyl-ethyl j.
or cycloheptyl-n-propyl.
The term aryl preferably comprises mononuclear groups
such as phenyl, which may be substituted in one or more
positions by substituents such as lower alkyl, hydroxy,
lower alkoxy or halogen.
Moreover in addition to the meaning above when R
:and Rl or the substituent of a lower alkyl group thereof
is an aryl group, this aryl group comprises 6 to 10 carbon
atoms and may be for example as mononuclear group a phenyl,
tolyl, xylyl, ethylphenyl, propylphenyl, isopropylphenyl,
butylphenyl, isobutylphenyl, sec;-butylphenyl,.tert.-butyl-
phenyl or naphthyl group.
If the substituents Rl, R2 or R3 can also repre~ent
together with the C(R)-N~ resldue, or CH-N< residue respecti~ely,
a heterocyclic. radical, it is preferably a 5-membered nitrogen-
containing ring such as pyrrolidine in proline and 4-hydroxy-
pyrrolidine in hydroxy-proline, and pyroglutamic acid.
. . :. , .
: ~ ' : .'' , ':;, : ' ,
..
-6- llS~
A h~terocyclic residue as substituent of an optional
substituted radical R, Rl, R2 and R3 may be a mono- or bicyciic,
a monoaza or diazacyclic radical of aromatic character such
as imidazolyl, as for example 4-imidazolyl, or indolyl, as
for example 3-indolyl radical.
.
Moreover in addition when R or Rl or the substituent
of a lower alkyl group thereof is a heterocyclic ring containing
one or more oxy~en, nitrogen or sulphur atoms this may be, for
example, aziridine, oxetane, thiopkene, furan, pyridine, aze-
pine, isox~zole, thiazole, pyrimidine, dia~epine, thiadiazol,
triazol, tria ine, or imidazole or indole as mentioned abo~e.
When R or Rl is a lower alkenyl group this may be
a straight or branched chain alkenyl group with 2 to 6 carbon
atoms, and may be, for exa~ple, an ethenyl, allyl, crotyl,
methallyl, pentenyl or hexenyl group.
Uhen R or Rl represents a lower alkynyl group this
may be straight or branched chain alkynyl group with 2 to
6 carbon atoms, and may be, for example, an ethynyl, propynyl,
butynyl, pentynyl or hexynyl group.
When R and Rl together form a polymethylene chain,
comprising a residue of 2 to 7 carbon atoms, this ~2y be
`~ for example -(CH2)2-, -(CH2)3~. -(cH2)4 ( 2 5 2 6
2 7 ( 2)2cHcH3(cH2)2- or -(CH2)2NH(CH2)2-
,
..
-
.
~L1S813~
_, _
The term etherified hydroxy is prefer~bly lower
alkoxy, such ~s methoxy, ethoxy, n-propyloxy, isopropyloxy
or n-butyloxy and etherified mercapto is preferably lower
alkylthio as for example methylthio, ethylthio, propylthio
or isopropylthio.
T~e compounds containing S-substituted dithio groups are
symmetrical or unsymmetrical residues of a compound of
formula I bound to the other residue of a compound of formula I
by a S-S-bridge, i.e. ~
A ^ S - S - B
wherein A and B are the same or different and each is
a residue of a compound of formula I formed by the loss
of a hydrogen atom from a carbon atom in one of the substituents :
R~ Rl, R2 or R3-
Examples of such compounds are those ha~ing the formulae
Ia and Ib
H2N CHCO t NH - CHC ~ NH - C - P - H
ICH2 I oL
s
R3 / IR2 ~ . I H2 0
H2N CHCO t NHCHCO t NH C- P H
\ / n Rl OH
.. . . . .. . . . . ..
~....................... . .. ~. .. . . . .
, , - , , . ,: ~. .. .~.
. .
--8--
t 1 2 ~ Rl o
CH2 R OH
I ~
I H t R2 ) Rl o
n R OH
.
Functionatly modified carboxy is, e.g. esterified
carbosy, especially lower alkoxycarbonyl, also phenyl-lower-
alkoxycarbonyl or carbamoyl.
i
When R, Rl, R2 or R3 is a group substituted by
~ R5, in which one or both the R4 and R5 groups are lower~
alkyl, these ~roups may be lower alkyl groups as defined
above. The -NR4R5 group including the different meanings
enumerated above may be for example, methylamino, dimethyl-
amino, methyl-ethylamino, ethyla~ino, diethylamino, propyl
amino, isopropylamino, dipropylamino or diisopropyl~mir.o.
The -NR4R5 groups in which R4 and R5 together form
a polymethylene chain containing up to 6 carbon atoms which
may optionally be interrupted by oxygen or nitrogen as for
instance as substituent of R and Ri and are preferably the
morpholino or piperidino group.
. . - , ,, ,. : :
~ . . : . ~ . . :
_g_
Furthermore when R or Rl is a group substituted by
aryloxy, the aryloxy group may be phenoxy, tolyloxy,
xylyloxy, diiodo-hydroxy phenoxy.
The term halogen may be bromine or iodine but is
preferably fluorine or chlorine.
Esters of the compounds of formula I are preferably
the esters of the compounds of formula I with low aIkyl
alcohols e.g. methanol, ethanol, n-propanol and n-butanol,
aralkyl alcohols e.g. benzyl alcohol and phenols e.g. phenol.
Other alcohols which may be used to form the corresponding
ester of the compound of formula I are alkanoyloxymethanols
e.g. acétoxymethanol or pivaloyloxymethanol; amino-lower-
alkanoyloxymethanols e.g. ~-amino-lower-alkanoyloxymethanols
such as glycyloxy-methanol, L-valyloxymethanol or L-leucyl-
oxymethanol; and also 3-hydroxy-phthalide and 5-indanol.
Salts of the compounds of formula I are salts with
either strong monobasic or polybasic or with inorganic or
organlc bases. Strong aclds include all those strong
acids e.g. hydrogen halide acids or allphatlc or aromatic
carboxyl~c and sulphonic acids which are capable of forming
salts with the amino group of the molecule and which are
physiologically acceptable to plants. Inorganic and organic
bases are those bases e.g. alkali metal and alkaline earth
metal hydroxides or alkylamines which are capable of forming
salts with the acidic hydroxyl group of the molecule and which
are physiologically acceptable to plants.
.,
', '
: ' , . .
~1~i&~
--10--
Particularly useful are compounds of formula I
wherei~ R and R1 may be the same or different and each is
hydrogen, deuterium, optionally substituted lower alkyl,or lower
alkyl substituted by cycloalkyl, aryl or by a mono- or bicyclic
monoaza-or diazacyclic radicals, optionally substituted
by one to three hydro~y or lower alkoxy groups; or Rl
represents, together with the -CR-N< residue to which it is
attached, the atoms required to complete a 2-pyrrolidinyl group;
R2 and R3 may be the same-or different and each is hydrogen,
optionally substituted lower alkyl, or lower alkyl substituted
by cycloalkyl, aryl, or by a mono- or bicylic monoaza or
diazacylic radical optionally substituted by one to three
hydro~y or lower alko~y groups or R2 or R3 each represents
to~ether with the -CH-N< residue to which it is attached, the
atoms required to complete the 2-pyrrolidinyl group;
and n is 0, 1, 2 or 3; as well as the esters and salts
with physiolog~callY acceptable alcohols, or acids or
bases, respecti~ely; and all optical isomers ther~of.
Preferred are compounds Or formula I wherein R and Rl
may be the same or different and each is hydrogen deuterium.
methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,
secondary butyl, tert~ary butyl, optionally substituted
by imidazolyl, indolyl, benzyl groups optionally substituted
by one to three hydroxy groups, lower aLkoxy, lower alkylthio,
amino or carboxy groups or Rl represents
'
.:
together with the -C~R)-N< residue to which it is attached,
the atoms required to complete a 2-pyrrolidinyl group;
R2 and R3 may be the same or different and e~ch can be
hydrogen, methyl, isopropyl, isobutyl, benzyl, aminobutyl,
hydroxymethyl, l-hydroxyethyl, 2-methylthioethyl, imidazoly-
methyl, or indolylmethyl, or R2 or R3, respecti~ely,
together with the -CH~< ~ residue to which it is attached,
represents the atoms required to complete a 2-pysroli~inyl
group; and n is 0,1,2 or 3; as well as the esters and
salts with pharmaceutically acceptable alcohols, or acids
or bases, re~poctively; and all optical isomers thereof.
Especially valuable and suitable for said utility
are compounds of formula ~, wherein R is hydrogen;
Rl is methyl; R2 and R3 may be the same or different
and each is hydrogen, methyl, lsopropyl, isobutyl,
aminobutyl, hydroxymethyl, l-hydroxyethyl, 2-methylthioethyl,
imidazolylmethyl or indolylmethyl, benzyl or R2 or R3
respectively together wlth the -CR-N or -CH-N resldue
to whlch lt ls attached represents the atoms requlred to
complete a 2-pyrrolidinyl group; and n is 0, 1, 2 or
3; and the esters and salts thereof with physiolcgically
acceptable alcohols or acids or bases, respectively;
and all optical isomers thereof.
: - . I -.,: : ~ .
., , ~ .
.. . - . ,. . , . , - ..
. . .
-
The production of the compounds of formula I is fully described
in Canadian application Serial No. 316,450 (United States Patent No.
4,213,969).
The agents according to the invention are prepared in a manner
which is in itself know by intimate muxing and grinding of active comEounds
of the formula I with suitable carriers, if desired with addition of
disEersing agents or solvents which are inert bowards the active compounds.
The active compounds may exist, and be used, in the follcwing processing
forms:
Solid processing forms: dusting agents, sprinkling agents,
granules, coated granules, impregnated granules and homogeneous granules;
Active compound concentrates which are dispersible in water:
wettable powders, pastes and emulsions:
Liquid processing forms: solutions.
In order to prepare solid processing fonms (dusting agents,
sprinkling agents and granules), the active compounds
- 12 -
-13-
are mixed with solid carriers. Ex~mples of carriers which
can be used are kaolin, talc, bolus, loess, chalk, limestone,
lime grits, attapulgite, dolomite, diatomaceous earth, preci-
pitated silica, alkaline earth metal silicates, sodium and
potassium aluminosilicates (feldspars and micas), calcium and
magnesium sulphates, magnesium oxide, ground plastics, ferti-
lisers, such as ammonium sulphate, ammonium phosphate,
ammonium nitrate and urea, ground vegetable products, such
as cereal flour, bark flour, wood flour, nutshell flour,
cellulose powder, plant extract residues, active charcoal and
the like, in each case on their own or as mixtures with one
another.
Granules ca~ be prepared by, for example, dissolving
the active compounds in an org~nic solvent,
applying the solution thus obtained to a granulated material,
for example attapulgite, SiO2, granicalcium or bentonite, and
then again evaporating the organic solvent.
- It is also possible to prepare polymer granules by,
for example, impregnating finished, porous polymer granules
such as urea/formaldehyde polymers, polyacrylonitrile and
polyesters, having a spx~iic surface area and an advantageous
predetermined absorption/desorption ratio,with the active
compounds, for example in the form of their solutions (in a
low-boiling solvent) and removing the solvent. Such
polymer granules can be applied in the form of micro-granules
with bulk densities of, preferably, 300 g/litre to 600 g/litre,
also with the aid of atomisers. Atomising can be effected
.: ... - . . : .
' '
~14~
over extensive treatment areas by means of aircraft.
~ ranules can also be obtained by compacting the carrier
with the active compounds and additives and then comminuting
the mixture.
Furthermore, it is possible to add to these agents
additives which stabilise the active compound and/or non-
ionic, anionic and cationic materials which, for example,
improve the adhesion of the active compounds to plants and parts
of plants (adhesives and glues) and/or ensure better wetta-
bility (wetting agents) and dispersibility (dispersing agents).
It ~s possible to use, for example, the following materi~ls
as adhesi~es: olein/lime mixture, cellulose derivati~es
(methylcellulose and carboxymethylcellulose), hydroxyethylene
glycol ethers of monoalkylphenols and dialkylphenols having
5 to 15 ethylene oxide residues per molecule and 8 to 9 carbon
atoms in the alkyl radical, ligninsulphonic acid, its aIkali
metal salts and alkaline earth metal salts, polyethylene gly-
col ethers (Carbowaxes), fatty alcohol polyglycol ethers
ha~ing 5 to 20 ethylene oxide residues per molecule and 8 to
18 carbon atoms in the fatty alcohol part, condensation
products of ethylene oxide and propylene oxide, polyvinyl-
pyrrolidonesj poly~inyl alcohols, condensation products of
urea/formaldehyde and latex products.
Water-dispersible active compound concentrates, i.e.
wettable powders, pastes and emulsion concentrates, are agents
which can be diluted with water to any desired concentration.
~heyconsist of active compound, carrier if desired additives
.
~ .
.
' . . ~ ~. .
. .
-15-
which stabilise the active compound, surface-active substances
and anti-foaming agents and, if desired, solvents.
The wettable powders and pastes are obtained by
mixing and grinding the active compounds with dispersing agents
and pulverulent carriers in suitable devices until homogeneity
is achieved. Examples of carriers are those mentioned above
for the solid processing forms. In some cases it is
advantageous to use mixtures of different carriers.
Examples of dispersing agents which can be used are: conden-
sation products of sulphonated naphthalene and sulphonated
naphthalene derivatives with formaldehyde, condensation pro-
ducts of naphthalene or of naphthalenesulphonic acids with
phenol and formaldehyde, and alkali met~l salts, ammonium
salts and alkaline earth metal salts of ligninsulphonic acid,
as well as alkylarylsulphonates, aIkali metal salts and alka-
line earth metal salts of dibutyln~phthalenesulphonic acid,
fatty alcohol sulphates, such as salts of sulphated hexa-
decanols and heptadecanols, and salts of sulphated fatty
a7cohol polyethylene glycol ethers, the sodium salt of oleyl
methyl tauride, di-tertiary acetylere glycols, diaIkyldilauryl-
ammonium chloride and alkali metal salts and alkaline earth
metal salts of fatty acids.
Examples of anti-foaming agents which can be used are
silicones.
The active compounds are mixed, ground, sieved and
strained with the abovementioned additives, in such a way that
the particle size of the solid component does not exceed 0.02
, , ,
.; . , , ~ , :
.. . . ..
', ' '' : ' . :
-16-
to 0.04 mm in the case of wettable powders and 0.03 mm in the
case of pastes. To prepare emulsion concentrates and
pastes, dispersing agents, such as have been listed in the
preceding sections, organic solvents and water are used.
Examples of suitable solvents are the following: alcohols,
benzene, xylenes, toluene, dimethylsulphoxide, N,N-dialky-
lated amides and trialkylamines. me solvents must be
virtually odourless and inert towards the active compounds
and s~l1dnotbe readily combustible.
Furthermore, the agents according to the invention
can be used in the form of solutions. For this purpose,
the active compound or several active compounds of the formula
I is/are dissolved in suitable organic solvents, solvent m~r
water -or mixtures of organic solvents with water.
The content of active compound in the agents described
above is between 0.1 and 95%, preferably between 1 and 80%.
Use forms can be diluted down to 0.001%. me
amounts used are as a rule 0.1 to 10 kg of active substance/
hectare, preferably 0.25 to 5 kg of active substance/hectare.
m e active compounds of the formula I can be formulated, for
example, as follows (parts are parts by weight):
Dustin~ a~ents:
m e following substances are used for the preparation
of a) a 5% strength dusting agent and b) a 2% strength
, .
-17
dusting agent
a) 5 parts o~ (l-RS)-l-(L-alanylamino)ethanephosphonous
acid and 95 p~rts o~ talc,
b) 2 parts of (1-RS)-l-(L-alanylamino)-2-methylpropane-
phosphonous acid
1 part o~ highly disp~rse silica and
97 parts of talc.
The actlve compounds are mixed and ground wYth the
carriers.
Granules:
-
The following substances are used ~or the preparationof 5% strength granules:
5 parts of (l-R)-l-(L-alanyl-L-alanyl-L-alanylamino)-
ethanephosphonous acid,
0.25 part of epichlorohydrin,
0.25 part of cetylpolyethylene glycol ether containing
8 mols of ethylene oxide,
- 3,50 parts of polyethylene glycol and
91 parts of kaolin (particle size 0.3 to 0.8mm).
The active substance is mixed with the epichlorohydrin
and dissolved in -cetone, , after which polyethylene
glycol and cetyl polyethylene glycol ether are added. ' The
solution ,thus obtained is sprayed onto kaolin and the acetone
is subsequently evaporated off in vacuo.
Wettable ~owders:
The following constituents are used for the prepara-
tion of a) a 50% strength wettable powder, b) a 25% strength
wettable powder and c) a 10% strength wettable powder:
,~
`, ~
-18~
a) 50 parts of (l-RS)-l-(L-valylamino)-ethanephosphonous
acid,
5 parts of sodium dibutylnaphthylsulphonate,
3 parts of a naphthalenesulphonic acids/phenol-
sulphonic acids/formaldehyde condensate, 3:2:1,
20 parts of kaolin and
22 parts of Champagne chalk;
b) 25 parts of the diethanolamine salt of the above
active compound,
5 parts of the sodium sal~ of oleyl methyltauride,
2 5 parts of a naphthalenesulphonic acids/form~lde-
hyde condensate,
O.5 part of carboxymethylcellulose,
5 parts of neutral potassium aluminium silicate
and
62 parts of kaolin;
c) 10 par~s Gf (l-R)-l-(L-alanylamino)-ethanephosphonous acid~
3 parts of a mixture of the sodium salts of
saturated fatty alcohol sulphates,
5 parts of a naphthalenesulphonic acids/formal-
dehyde condensate and
82 parts of kaolin.
The active compound indicated is absorbed onto the
appropriate carriers (kaolin and chalk) and is then mixed and
ground. Wettable powders of excellent wettability and
suspensibility are obtained. Suspensions of any desired
active compound concentration can be obtained from such wetta~le
~,
powders by dilution with water Suspensions of this type
, .. .. .
, - . . ~. ,
~ & ~
--19--
are used for combatting weeds and wild grasses in crops
of plants by the pre-emergence process, and for the treatment
of 1AWnS .
Paste:
The follo.wing substances are used for the prep~ation
of a 45% strength paste:
45 parts of (l-R)-l-(L-alanyl-L-alanyl-L-alanyl-L-
alanylamino)-ethanephosphonous acid
5 parts of sodium aluminium'silicate,
14 parts of cetyl polyethylene glycol ether containing
8 mols o~ ethylene oxide,
1 part of oleyl polyethylene glycol ether containing
5 mols of ethylene oxide,
2 parts of spindle oil,
23 parts of water and
10 parts of polyethylene glycol.
The active compound is intimately mixed and ground
with the additivesin apparatus ~ which i8'~ suitable for this
purpose. A paste is obtained, from which suspensions of any
desired concentration can be prepared by dilution with water.
me suspensions are suitable for the treatment of lawns.
Emulsion concentrate:
~ ,or the preparation of a 25% strength emulsion concen-
trate.
' ' . ~
-20-
25 parts of (l-R)-l-(L-alanyl-L-alanylamino)-ethane-
phosphonous acid,
5 parts of a mixture of nonylphenol polyoxyethylene
and calcium dodecylbenzenesulphonate,
35 parts of 3,~,5-trimethyl-2-cyclohexen-1-one and
35 parts o~ almethylformamide
are mixed with one another. This concentrate can be diluted
wi~hwat#rto @ve emulsions of suitable concentrations.
Instead of the particular active compound indicated
in the above formulation examples, it is also possible to use
other compounds from amongst those included in the formula I.
m e active compounds contained in the agents accord-
ing to the invention influence the plant growth in various
ways. m us they inhibit, delay or suppress, in parti-
cular, the growt_ and germination. They there~he have a post-
emergent herbicidal action as well as a growth ~nh~biting
action.
Agents according to the lnvention, which contain at
least one compound of the formula I as the active component,
are suitable, in particular, for i~hibiting and suppressing
p~ant growth in monocotyledonous and dicotyledonous plants by
post-emergent treatment of the sown areas or of the plants,
such as shrubs, trees, leguminous crops, sugar cane, onion and
potato tubers, fruit trees and vines and, in particular,grasses,
cereal crops, tobacco, soya and ornamental plants.
.. . .
; ; , . -
.. . .~ . .. .
-21-
The action achieved, in particular, by the active com-
pounds of the formula I is the desired reduction in plant
size, especially the height of growth. In general, a certain
change in the form of the plant is associated with this.
In direct association with the reduction of the height of
growth, the plant is strengthened. The leaves and stem
develop more strongly. me resistance to kinking of mono-
cotyledonous plants is increased by shortening the internodaldistances. Crop losses due to a thunderstorm, continuous
rain and the like, which usually lead to lodging of cereal
crops and leguminous crops, can be largely prevented in this
manner and harvesting can thus be made easier. As a side
effect, reduced height of growth of useful plants leads to a
sa~ing of fertilisers. This also applies, in the same way,
to ornamental plants, ornamental lawns, sports fields or other
grassed areas.
However, one of the most important problems of pure
grass plantings is the actual cutting of the grass, whether in
public parks in urban areas, on industrial sites, on playing
fields or alongside motor-roads, aircraft landing strips,
railway emb~nkments or the sloping banks of waterways. In
all these cases lt is necessary to mow the lawn ox cut the
growth of grass periodically. This is not only very expen-
sive in terms of labour and machinery, but, in the transport
sector, also in~ol~es considerable dangers for the personnel
concerned and for the occupants of ~ehicles.
.
.
.
': .
.
-22- ~ 8~ ~
There is therefore, particularly in areas with large
traffic networks, an urgent need on the one hand to maintain
and care for the greensward which is necessary to strengthen
road verges and embankments on traffic routes and, on the
other hand, to keep it at a medium height of growth during
the whole vegetation period, using simple measures. This
need is met in a very favourable mAnner by applying active
compounds of the formula I.
By treating trees, shrubs and hedges, in particular
in urban and industrial areas, with compounds of the fonmula L
thelabaur-inb~E~e wingwD~kcznbe reduoedin an analogous manner. -
T~e growth of shoots and/or the fertilityof fruit trees and vines can also be advantageously influenced
by using the active compounds of the formula I.
Ornamental plants with pronounced longitudinal growth
can be grown as compact pot plants by treatment with the active
compounds mentioned.
The active compounds of the formula I are also used
for inhibiting the growth of undesired side shoots, for example
in tobacco and ornamental plants, whereby the labour-intensive
m~nual breaking off of these shoots is avoided, and furthermore
for the inhibition of sprouting in the case of stored tubers,
for e*ample in the case of tubers of ornamental plants and in
the case of onions and potatoes, and finally for increasing the
yield in the case of crop plants having an intense vegetative
growth, such as soya and sugar cane, by accelerating the trans-
ition from the vegetative growth phase to the generative growth
phase through application of active compounds of the
formula I.
.. ..
.. ~ . . , . ~.. ;. ,
. .
.. . . , . -
8`~Z
-23-
The active compounds of the formula I are preferably
employed for inhibiting the growth of weeds, including
perennial weeds, grasses, especially perennial grasses,
such as Cyperus species and the like, and of cereal crops,
tobacco, soya and ornamental plants.
~ he amounts used vary and depend on the time
of appllcation. In general, they are between 0.1 and 5 kg of
active compound per hectare for the treatment of existlng
crops, preferably up to 4 kg per hectare.
The action of the active compounds according to the
definition is directed towards the germinating seed(pre-
emergent action) but is preferably directed towards the parts of
the plant which are above ground ( contact action) in particular
the leaves.
The action as a powerful growth inhibitor is shown
by the fact that most of the species of plants treated in a
post-emergent manner stop growing after an experimental period
of three weeks, the partsof the plant treated assuming a dark-
green coloration. However, the lea~es do not fall.
In the case of some spec~es of plants, this growth
inhibition already occurs at a dosage of 0.5 kg/hectare and
less and wlthin several days after treatment.
Since not all species of plants are equally
powerfully inhibited, it is possible to use the active com-
pounds selectively when a particular low dosage is chosen.
. .
, . . .
Z
-24-
The active compounds of the formula I are also
interestLng combination partners for a number of herbicides
of the diphenyl ether, phenylurea and triazine series for use
on cereal crops, maize and sugar cane 2nd in fruit growLng and
viticulture.
In areas with an increased danger of erosion, the
active compounds of the formula I can be used as growth inhi-
bitors on the most diverse crops.
In thls case, the weed co~er is not removed but only
nh~bited to such an extent that it can no longer compete with
the crop plants.
._ ., . . . . .. __ ... . . .. . .
The following Examples further illustrate the
present inventlon.
Use Examples 1 and 2
The following test methods were used to demonstrate
the usefulness of the actlve compounds as herblcides
(post-emergent) and as growth inhibitors:
Post-emergent herbicidal action (contact herbicide)
The plants of 7 weeds and crop plants, both
monocotyledonous and dicotyledonous, ~ere sprayed after
emergence ( in the 4-leaf to 6-leaf stage) with an
aqueous actlve co~pound emulsion in a dosage of
4 kg of actlve substance per hectare, and the plants
were kept at 24- 26C and a relative atmospheric humidity
of 45-60%. The test was evaluated 5 days and 15
days after treatment and the result is given ln the
.~ following Table I.
...
. . . . .
. : ,. . .
~1~)88~32
- 25 -
TABLE 1 - POST EMERGENT HERBICIDAL ACTION
CH3 CH3 CH3 CIH3 3
compound H2N-CH-CONHCHP(OH)2 H2NCHCO[NHCHCO]2NHCHP(OH)2
L R L L R
plant -
Avena sa~iva . 4 5
Setania
Italica 2 3
Lolium
perenne 3 4
Solanum
lycopersicum 3 2
Sinapis
alba 2 2
Stellaria
media 2 4
Phaseolus
vulgaris _
9 = plant(s) undamaged (as untreated control) --
8-2 = intermediate stages of damage
The results demonstrate that the compounds according to
the present invention which were tested exhibited a pronounced
contact herbicidal action on some plants and, as a symptom of
the growth inhibiting properties, halted the growth of many
plants.
.
:-
'~ ' . ` ~ .. . -. . :' . ". ~ . . ' .,
,
-26-
Growth inhibition in ~rasses
Seeds of the grasses Lolium pere~ne, Poa pratensis,
Festuca ovina and Dactylis glomerata were sown in plastic
bowls containing an earth/peat/sand mixture (6:3:1) and were
watered normally. Every week the emergent grasses were cut
back to a he-ight of 4 cm and, 40 days after being sown and 1
day after the last cutting, were sprayed with aqueous spray
liquors o* an acti~e compound of the formula I. The
amount of active compound corresponded to 5 kg of active
substance per hectare. The growth of the grasses was evalu-
ated 10 and 21 days after application.
Growth inhibition in cereals
,
Spring wheat tTriticum aestivum), spring barley
(Hordeum vulgare) and rye (Secale) were sown in sterilised
earth in plastic beakers and the plants were grown in a green-
house. 5 days after being sown, the cereal shoots were
treated with a spray liquor of the actlve compound. The
application to the leaves corresponded to 6 kg of active
compound per hectare. Evaluation is carried out after 21
days.
The compounds of Examples 3-6, 8, 17 and 18
caused a pronounced inhibition of growth of grasses, the
compounds of Examples 8, 13 and 4 were most active inhibi-
ting the growth of cereals.
' ',.~ '. '
. ' . ".' . '. '` . -
- 27 -
Inhibition of the growth of side shoots of tobacco plants.
Eight weeks after sowing, tobacco Nicotiana tabacum
(variety Xanthi) are transplanted to pots in a greenhouse,
normally watered and treated weekly with nutrient solution.
Two weeks after potting, there are chosen per treatment
three plants; of these plants one remains untopped and from
the two others the growth tip is removed five days before
treatment.
Per plant there is then sprayed, laterally from above
onto the leading shoot and the upper leaf axils, 10 ml of
liquor containing active substance (concentrations: 2.6;
1.3 and 0.6 % corresponding to 6.3 and 1.5 kg per hectare
in the open). A part of the liquor consequently runs down
the petioles and into the remaining lower leaf axils (con-
tact with side-shoot buds).
After setting up of the tests in the greenhouse and
watering, the tests are evaluated 4 and 14 days after
application of the test liquor.
-
Contact effect and systemic effect are evaluatedseparately.
Contact effect: Assessment of the 6 uppermost side
shoots;
Syternic effect: Assessment of the uppermost side
shoots.
Excellent results are obtained in these tests with the
active substances of the invention, such as in particular
with those of the Example 7.
.. ,
....
-28- ~ 2
Example 3
aj RS -l-Aminoethanephosphonous acid (8.25g., O.075M)
was dissolved in water (375 ml.) and ethanol (190 ml.)
and the solution was cooled tP 10. Sodium bicarbonate
(A.R. grade, 12.75g., O.L5M) was added portionwise with
stirring and the resulting solution was cooled to 0.
A solution of the N-hydroxysuccinimide ester of N-
benzyloxycarbonyl-L-alanine (24g., 0.075M) in hot ethanol
~260 ml.) was added over a period of lO minutes maintaining
the internal temperature at 0.
The heterogeneous mixture was stirred for 2 hours
at 0 and then 24 hours at room temperature. The clear
solution was evaporated at room temperature to give a ~hite
gummy solid. Treatment of this ~esidue with cold dilute
hydrochloric acid (2N., 150 ml.) gave a white powdery
solid which was allowed to stand 2 hours at room tempera~ure.
The mixture was di~uted with an equal volume of water and
allowed to stand 24 hQurs at ~. Filtration gave a
mixture of the l~S) and l~R)~-diastereomers of l-[(N-benzyI-
oxycarbonyl-L-alanyl)amino~-ethanephosphonous acid
~l2.2g., m.p. 175-6~, L~DO -45.P (2% in glacial acetic
2Ci~ .
. ~ :, , . . , :
.: , ,~: ,: ~
,, :, :;., . ``' '
:`. , ::" :,, :
8i~Z
-29-
b) This mixture of diastereomers of l-[(N-benzyloxy-
carbonyl-L-Alanyl)amin~-~hanephosphonous acid (12g.) was
added to a solution of hydrogen bromide in glacial acetic
acid (50 ml., 45% w/w) at 0 and the mixture was stirred
for thirty minutes. The solution was allowed to warm
up to room temperature and then evaporated to an oily
residue. This residue was dissolved in dry methanol
(60 ml.) and propylene oxide was carefully added ~ith
cooling. The mi;;ture was stirred for two hours at room
temperature and allowed to crystallise at 0. It gave
a mixture of diaste~eomers of l-(L-alanylam~no)-ethane-
phosphonous acid [m.p. 276 decomp., ~a~D -75.6 (2% in
water~ .
.
Example 4
The procedure described in Example 3a was repeated
using ~IR) -l-aminoethanephosph~nous acid i~stead of
RS -l-aminoethanephosphonous acid to give tIR) -1-
[N-benzyloxycarbonyl-L-alanyl)amino] -e~hanephosphonous
acid. m.p. 180-2 decomp., [~3D0 -60 (2% in glacial
acetic acid). [The (+)-~-methylbenzylamine salt of this
compound had m.p; 206-7 decomp. and [~ 20 _44.~ (2% in
methanol)~.
.
, . :
.
. .
". ., ~' ' ,
. :
- . . . .
. 1. ~ . -
-30-
By the same procedure described in Example 3b, this
compound was converted to (lR~ -l-(L-alanylamino)-
ethanephosphonous acid. m.p. 276 decomp., ~a~20 -80.1
(27~ in water).
Example S
a) ~ l-Aminoethanephosphonous acid (3.4g., 0.03LM)
was dissolved in water (15S ml.) and ethanol (186 ml.) and
the solution was cooled to 10. Sodium bicarbonate
(A.R.grade, 5.25g., 0.062M) was added portionwise with
stirring and the resulting solution was cooled to 0.
A solution of the N-hydroxysuccinimide ester of N-benzyloxy-
carbonyl-L-alanine (9.9g., 0.031M) in hot et~anol (44 ml.)
was added over a period of 10 minutes maintaining the
internal temperature of 0. This mixture was stirred ,or
2 hours at 0 and 24 hours at room temperature. Th~ cIear
solution was evaporated at r~om temperature to give a
gummy sol.id. This material ~Yas stirred with ethanol
(50 ml.) and the insoluble material was removed by filtration.
The iltrate was evaporated to dryness, red~.ssolved in
absolute ethanol and made just acid with a solut~on of
hydrogen chloride in ethanol. The cloudy solution was
diluted with ether ~75 ml.) and a white solid was obtained
which was dissolved in 75 ml. ethanol and clarified with
.. . . ....
. : ...... ..
,. .. . ..
- . ., . ~ ";.
- , ~ . , . ,, - ..
- . . : . ...
-3~ 8~Z
filter-aid. Evaporation of the filtrate gave ~lS)
[(N-benzylox~carbonyl-L-a~anyl)amino] -e,hanephGsphonous
acid m.p. 143-5 decomp., t~20 + 33.8 (2% in glacial
acetic acid. CThe (+)-~-methylbenzylamine sal~ of this
compound had m.p. 205-6 decomp., and [~3D0 + 19.8
(2% in methanol)] .
b) By the same procedu~e described in Exampl~
this compound was converted to [l~S)~ -l-(L-alanylamino)-
ethanephosphonous acid m.p. 274 decomp., [~ 20 ~ 115
(2% in water).
Example 6.
a) The procedure described in Example 3a was repeated
to give a mixture of the lS_ and lR- - diastereome~s of
l~[(N-benzyloxycarbonyl-L-alanyl)amino]-ethanephosphonous
acid m.p. 175-6, [a]20 _45.7 (2% in glacial acetic acid);
(the filtration liqjuors from which it w~s obtained being
set aside for use in Example-6b). This solid was converted
to its (~ methylbenzylamine salt in ethanol so~vent and
recrysta~ised from ethanol to constant melting point and
constant specific rotation, identi~ to that described in
~' Example ~a, namely, m.p. 206-7 decomp., and [a]20 -44 7
(2% in methanol).
- . , ~ ~.
.
-l . -: ; . - ': .
., , . . . : . .
- . . , . - .
- ,:
.. . ., .
- . .
- : ;
- , .. .. ..
,, , , :
-32~ 8 8~
By the procedure described in Example 3b this salt
was converted to (~ l-(L-alanylamino)-ethanephosphonous
acid m.p. 27~ decomp., [~]D -80.1 (~% in water).
b) The filtration liquors obtained in Example 6a: were
evaporated to an oil which was dissolved in ethanol and the
splid which formed was collected by filtration. The
filtrate was evaporated to dryness and the oil so obtained
was stirred with acetone. The waxy solid which formed was
collected by filtration and the filtrate again evaporated
to dryness. The resultant oil was dissolved in water,
extracted successively with ether, propylene oxide, and
finally petroleum ether. Evaporation of the aqueous
portion gave an oil which on ~reatment with (~ -methyl-
benzylamine in isopropanol solvent gave the (+)-~-methyl-
benzylamine salt of (lS) -l-[(N-benzy~oxycarbonyl-L-alanylj-
amin~ -ethanephosphonous acid m.p. 205-6 decomp., [~ D~1~.5C
(2% in methanol), identical to that described in Example 3a.
By the procedure de~cribed in Example 3b this salt
was converted to ;~lS) -l-(L-a;anylamino)-ethanephosphonous
acid m.p. 275 decomp.,[~]D + 115 (2% in water) identical
t~ that obtained in Example 3b.
Exam~le 7
a) ~lR) -l-(L-alanylamino)-ethanephosphonous acid
(1 8g., O.OlM) was dissolved in 2 mixture of water (50 ml.)
rt ' ' '
,: . , , ' ' . .:~ ' " ' : ', ' ':
' ~ ' ` ` ,.. . ", ~ ' .. ,, , ., ., ' '
, ~', . ' '.'' ''' '''''' ".. ''.
--33--
~nd cth~nol (25 ml.) and the ~oiution uas cooled to
10 sodium bicarbonate (A.R. erade t.7g., 0.02M)
addcd portlon~i~e and the ~oluticn was cooled to 0-.
A solution Or the N-hydroxyRuccinimide eotcr o~ N-~enzyl-
oxycarbonyl-~-al~nine(3.2g., O.OlM3 ~n ~lOt ethanol(35 ml.)
was added over a por~od of 10 m~nutcs mainta~nln~ the
internal temperature at 0-. The he~erogeneous m~xture.
~as st~rred for 2 hours ~t 0- and then 24 hour~ at room
tcmperature. The resulting clear solut~on ~as evaporated
at roo~ temperature to give a w~te 6~mmY solid. Thi~
re~idue ~a~ stirred wit~ dilute l~ydrochlor~¢ acid(2~.25 m~
~or 2 ~ours at room temper~ture ~nd al;o~ed to crystall~se
at 0. Filtration gave ~lR) -l-L(N-benzyloxycar~onyl-L-
alanyl)-L-alanylamino~ -ethanephosphonous acid~
having melting point 221 , ~a] - 73.6 (1% glacial acetic
acid).
b) By the same procedure as described in ExamDle 3b
~ [(N-benzyloxycarbonyl-L-alanyl)-L-alanylamin~ -
ethanephosphonous acid was converted to Ll-(r~)~ l-(L-alanyl-
L-alanylamino)-ethanephosphonous acid~
having melting point 263-264, La~ DO _ 112.7(1% in water).
.
.
,
. .
, .
1~J~
-34-
Example 8
The pr~cedure described in Example7a was repeated
using (IR) -l-(L-alanyl-L-alanylamino)-ethanephosphonous
acid instead o~ (lR) -l-(L-alanylamino)-ethanephosphonous.
acid to give (lR) -1- (N-benzyloxycarbonyl-L-alanyl)-
(L-alanyl-L-alanyl~no)-ethanephosphonous acid, of melting
point 242 ~a7 20 -114.3 (1% in 2N NaOH).
By the same procedure described in Example 3b, this
compound was converted to (lR) ! -1- (L-~lanyl-L-alanyl-
L-alanylam~no)-ethanephosphonous acid, of melting point
67 [~ 20 _ 136.3 (1% in water).
Example g
The procedure described in Example 7a was repeated
usinq (lR) -l-(L-alanyl-L-alanyl-L-alanylamino)-ethane-
phosphonous acid instead of; (lR) -1-(L-alanylamino)-ethane-
phosphonous acid to give; 51~) -1- (N-benzyloxycarbonyl-L-
alanyl)-L-alanyl-L-alanyl-L-alanylamino -ethanephosphonous
acid, of melting point 274-275,~a~2 133tO 4~ in
2N NaOH).
By the same procedure described in Example 3b this
compounc was converted to (1~) -I-(L- alanyl-L-alanyl-~-alanyl-
L-alanylamino)ethanephosphonous acid, of melting polnt
288-289, ~a32 - 154.2 (0.6% in water).
~.:., - . ,
.~:
.,~,. ., . ~.. .~.. ..
~, . . 1 . ;~
li';:~8~13Z
- 35 -
Example 10
a) The procedure described in Example 3a was repeated using
-l-amino-2-methylpropanephosphonous acid instead of
-l-amino-ethanephosphonous acid to give a mixture of the
R_ and lS-diastereomers of l-[(N-benzyloxycarbonyl-L-ala-
nyl)amino]-2-methyl-propanephosphonous acid as a viscous
pale yellow oil, [a]D - 17 (2 % in ethanol).
b) By the same procedure described in Example 3b, this
product was converted to a mixture of the diastereomers
of l-(L-alanylamino)-2-methylpropanephosphonous acid,
m.p. 260 decomp., [a]D -40 (1 ~ in water).
Example 11
(a) The procedure described in Example 3a was repeated
using [l-(-)]-l-amino-2-methylpropanephosphonous acid
instead of RS-l-aminoethanephosphonous acid to give
[l-(-)-l-[(N-benzyloxycarbonyl-L-alanyl)-aminol-2-methyl-
propanephosphonous acid m.p. 174-5, [a]D -70, (1 % in
glacial acetic acid). [The (+)-a-methylbenzylamino salt
of this compound had m.p. 183-5 and [a]D -43.9 - 49.9
(2 % in methanol)
. ~,
; `:' ,'' ' :' '
- ~
~ 36-
,
-(b) By the same procedure as described in Example3~,
this conlpound was converted to [(l-(-)l-l-(L-alanylamino)-
2-methylpropanephosphonous acid m.p. 271-2 decomp., ~]D 54'
(1% in w~ter~
Example 12
(a)The procedure described in Example 5a~ was repeated
using tl-(+)]-l-amino-2-methylpropanephosphonous acid
instead of tl-(S)~ -l-aminoetkanephosphonous acid to give
[1-(+9 -1- [(N-benzyloxycarbonyl-L-alanyl)amin~ -2-methyl-
propanephosphonous acid as an oil. CThe (+)-~-methylbenzyl-
amine salt of this compound had m.p. 184-5 and [~]20 + 15.7
(2Z in methanol) ~
(b) By the same procedure as described in Exampl~e ~, this
compou~ was converted t~ rl-(+)~-l-(L-alanrlamino)-2-methyl-
propanephosphonous acid m.p. 2Ç3-4 decomp.[~ D0 ~ 79.6
(1% in water)
Example 13
.... .
a) The procedure described in Example 3a was repeated using the
N-hydroxysuccini~ide ester of N-benzyloxycarbonyl-L-valine instead
of the N-hydroxysuccinimide ester of N-benzyloxycarbonyl-L-al2nine.
A mixture of the ~S- and ~R- diastereomers of l- (N-benzyl-
oxycarbonyl-L-~alyl)amino; -ethanephosphonous acid, m.p. 202,
[~ 20 -38.5 (2% in glacial acetic acid) was obtained~
~" . .~ ,
- . ~ .
'' ' : ':
~ _37_ ~ Z
b) By the s2m2 procedure described in Example 3P this product was
con~erted to a mixture of diastereomers of l-(L-vzlyl~mino)ethane-
phosp'aonous acid, m.p. > 260, i~, 25 _30 ~1% in water).
xample 14
a) The procedure described in Example ~a was repeated using th~
hydroxysuccinimide ester of N-benzyloxycarbonyl-~-alanine instead
of the ~-hydroxysuccinimlde ester of N-benzyloxycarbonyl-L-alanine.
A mixture of the 1~ S)- and l-~R)-diastereomers or l-[(N-benzyl-
oxyc~rbonyl-D-alanyl)amino~ -ethanephosphonous acid, m.p. ~75-176,
, ~ 22 ~51.5 (2% in glacial ace~ic acid) was~obtained
b) By ~he same procedure described in Example3b this prod~ct
~as converted to a mixture of diastereomers of l-(D-alanylamino?-
e~h2nephosphonous acid, m.p. >260, L~J24 +65.5 (2% in water)
Example 15
a) The procedure described in Exam~le 3a was repeated using
he N-hydroxysuccir.imide ester of N-benzyloxycarbonylglycine
instead of the N-hydroxysuccinimide ester of N-benzyloxycarbonyl-
L-alanine. A racemic mixture of the S- and R-
enantiomers of l-(N-benzyloxycarbonylglycyl)-aminoethane-
phosphonous acid, m.p. 86-87 was obtained.
. .
:
' . ' :
S~2
- 38 -
b) sy the same procedure described in Example 3b this pro-
duct was converted to the racemate of l-glycylaminoethane-
phosphonous acid, m.p. 254-255.
Example l6
lRS-l-(L-alanylamino1-ethanephosphonous acid (1.8014g,
O.OlM) was dissolved in a solution of cold water (lO ml)
and sodium hydroxide (0.40g., O.OlM) and the mixture was
stirred for five minutes. The mixture was evaporated to
dryness, stirred with absolute ethanol, and filtered to give
the sodium salt of lRS-l-(L-alanylamino)-ethanephosphonous
acid.
Example 17
lRs-l-(L-alanylamino)-ethanephos~honous acid (lg.) was
d~ssolved in a solution of absolute ethanol saturated with
dry hydrogen chloride (50 ml). The mixture was evaporated
to dryness to glve the hydrochloride of lRS-l-tL-alanylamino)-
ethanephosphonous acid.
Example 18
-
In a way analogous to the foregoing examples, the
following compounds have been obtalned as well.
l-(glycylamino)-anisyl-phosphonous acid m.p.255
(decomposition)
l-(glycylamino)-2-methylpropanephosphonous acid,
m.p. 253
l-(L-phenylalanylamino)-ethanephosphonous acid,
m.p. 172
glycylaminomethylphosphonous acid.
. ..
:, , ` - ` ~ . :
.
