Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
1~3~
BIOLOCICALLY ACTIVE AMIDE DERIVATIVES
_
This application is a division of Serial No. 397,435
filed March 2, 1982.
This invention relates to substituted benzamide
derivatives useful as herbicides and fungicides, to
processes of combatting weeds and fungal infestations and
to herbicidal and fungicidal compositions.
Substituted benzamide derivatives have previously been
proposed for use as herbicides, by way of example, the
compounds disclosed in UK Patent Specifications No.1209608
and 1395802 may be mentioned.
According to the present invention, there are provided
amide derivatives of the formula (I)
Rl- C - N - CH -XR3
~2 E
(I)
wherein Rl is an optionally substituted alkyl, alkenyl,
aryl, heterocyclyl, benzyl, or heterocyclylmethyi
radical;
R2 is hydrogen, or an optionally substituted alkyl,
alkenyl, benzyl, or heterocyclylmethyl, radical,
X is oxygen, sulphur, or an -NH- group'
R3 is an optionally substituted alkyl or alkenyl
radical when X is oxygen or sulphur, or is an optionally
substituted alkanoyl radical when X is -NH-,
and E is a -CN, -CONH2, -CSNH2, or -CoNR4R5
group wherein each R4 and R5 is hydrogen or an
optionally substituted alkyl or alkenyl group.
..a
2 ~L23~a~
~ len the group R1 is an optionally substituted alkyl
or alkenyl radical, it may be for example Cl 5 alkyl or
C3_5 alkenyl radical. Examples of substituents include
C1-C4 alkoxy, Cl-C4 alkylthio and halogen (i.e.
fluorine, chlorine, bromine or iodine).
~ en Rl is a benzyl radical optionally substituted
in the phenyl ring, examples of substituents include
halogen (fluorine, chlorine, bromine or iodine), Cl-C4
alkoxy, Cl C4 alkylthio, nitro, cyano, Cl-C4
haloalkyl (e.g. CF3), and Cl-C4 alkyl (e.g. CH3).
There may be from one to five substituents, which may be
the same or dif~erent.
When Rl is an optionally substituted aryl group it
may be a phenyl or naphthyl radical. Examples of
substituents which may be present include fluorine,
chlorine, bromine, iodine, Cl-C4 alkoxy,
methylenedioxy and ethylenedioxy, Cl-C4 alkyl, Cl-
C4 alkylthiot Cl-C4 haloalkyl (e.g. CF3) nitro and
cyano. There may be from one to three or more substituents
which may be the same or different. When Rl is a
substituted phenyl radical the substituents are preferably
in the 3, 4, or 5 positions. ~hen a methylenedioxy or
ethylenedioxy substituent is present, it preferably is
attached to the 3 and 4 positions of .he phenyl ring. A
halo~en substituent (e.g. Cl or Br) may also be present in
the 4- or S-position, or both, in such compounds.
~ en Rl is an optionally substituted heterocyclyl
radical, it may for example be a furyl, benzfuryl, thienyl,
pyridyl, thiazolyl, or benzthiazolyl radical. E~amples of
substituents which may be present include those listed above
for the case when Rl is a substituted phenyl radical.
There may be from one to three or more substituents which
may be the same or different.
~ihen Rl is an optionally substituted
heterocyclylmethyl radical, the heterocyclyl qroup may be
3 12~
for example a furyl, thienyl, pyridyl, thiazolyl or
ben~thiazolyl group. Examples of substituents w~ich may be
present in the heterocyclyl group include those described
above for the case when Rl is a substituted phenyl
radical.
R2 is preferably hydrogen but when it is not, then it
may be an optionally substituted alkyl group, for example an
Cl-C4 alkyl group. Examples of substituents which may be
present include fluorine, chlorine, bromine, iodine, and
Cl-C4 alkoxy~ When R~ is an optionally substituted
alkenyl group it may be for example an alkenyl group of from
3-5 carbon atoms. Examples of substituents which may be
present include those listed above for the case when R2 is
an alkyl group.
~7hen R2 is an optionally substituted benzyl group,
the substituents may include those described above for the
case when Rl is substituted benzyl.
When R2 is an optionally substituted heterocyclyl
methyl group, the heterocyclyl ring may be for example a
furyl, thienyl, pyridyl, thiazolyl, or benzothiazolyl
ring. Substituents which may be present include those
described above for the case where Rl is a substituted
phenyl radical.
When R3 is an optionally substituted alkyl or
alkenyl radical it may have any of the values described
above for the group R2.
When R3 is an alkanoyl group (i.e. when X is NH) it
may for example have from 1 to 4 carbon ato~s (e.g. it may
be a formyl, acetyl, or propionyl group).
-
//
el,
4 1~3~8~4
R4 an~ R5 are preferably hydrogen, but when they arenot, they may be optionally substituted alkyl or alkenyl
group it may have any of the values defined above for the
group R2 when it is an optionally substituted alkyl or
alkenyl radical.
Within the above definition, one sub-class of
compounds according to the invention comprises those
compounds whexein R2 is hydrogen. ~ithin this sub-class,
a further sub-class comprises those compounds in which E
is a cyano group, X is O or S, and ~3 is Cl-C~ alkyl
A group within the latter sub-class includes those
compounds in which R1 is phenyl or heterocyclyl. Within
the latter group, a sub-group includes compounds in which
the heterocyclyl or phenyl group is substituted, for example
by alkyl, alkoxy, methylenedioxy, or halogen, for example
fluorine or chlorine. In such compounds the groups or atoms
are preferably located in the 3, 4 or 5 positions of
the phenyl ring.
The structural formula (I) given above is believed
to be the one which best represents the structure of the
compounds. For some compounds within the scope of the
formula (I) it may be possible in principle for tautomeric
forms of the compound to exist, in which a hydrogen atom is
transposed to another part of the molecule and the chemical
bonds between the atoms of the molecule are consequently re-
arranged; thus, where ~1 is hydrogen, it is possible in
principle for the molecule to exist in the alternative form
(II)
Y R2
~ C N C -- ~R3
~/" I I
OH CN
(II)
r) J~d~
~ le structura] formula (I) is intended to represent
and include such tautomeric forms, insofar as they may
exist. The structural formula (I) is also intenc~ed to
include any physically clistinguishable modifications of
the compounds which rnay arise, for example, from different
ways in which the molecules are arranged in a crystal
lattice, or Erom the inability of parts of the molecules
to rotate freely in relation to other parts, or from
geometrical and or optical isomerism, or from intra-
molecular or inter-molecu].ar boncling, or otherwise.
Particular examples of compounds according to the
invention are listed in Tab ~ _ -
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~OTES
The abbreviations used in Table I are standard chemical
symbols. Thus the symbols Me, Et, Pr and Ph stand for
metnyl, et~yl, prop~l, and rhenyl groups respectively, and
the symbols F5.C6. and 3-C1-5-~02.CGH3. r for
example, stand for pentafluorophenyl and 3-chloro-5~nitxo-
phenyl respectively.
Melting points are given ~or most compounds in the table~
~ere the compound is an oil, a refractive index
measurement or nuclear magnetic resonance ~NMR) data are
given in the ~otes below. In the NMR information, the
symbols have the following meanings:-
s singlet
t triplet
-- q quartet
m multiplet
d doublet
Chemical shi~ts(S) are quote~ relative to tetramethyl-
silane. The solvent used was deuterochloroform.
Notes for individual compounds follow:~
21
(a) Refractive index nD = 1.5233
21
(b) Refractive inde~ nO = 1.5197
(c) NMR data: S=1.3 (3H,t), 3.45 (3H,s), 3.7 (2H,q),
5.95 (H,S, broad), ca 7.5 (4H,m)
(d) ~R data: ~=1.5 (6H,d), 2.35 (3H,s), 3.3 (3H,s),
4.1 (lH,m), 5.5 (lH,s), ca. 7.2 (aH,m).
?~
~e~ data: ~ =L.5 (6H,d), 2.35 (3E~s~, 3.3 (3H,s),
4.1 (l~,m), S.S (lH,s), ca.7.2 (4E~,m)
f) NMR data: ~=1.3 (3H,t), 2.4 (3~,s), 3.7 (2H,q),
5.95 (lH,s,broad), ca. 7~3 (4H,m)
g) N~R data: ~2.4 (3H,s), 3.1 (3H,s), 3.4 (3EI,s),
ca. 6.1 (lH,s,very broad~, ca. 7.3 (4H,m)
h) NMR data~ 3.1 (3His)/ 3.4 (3H,s), 6.1 ~s,v~ry broad),
ca. 7.2 (4H,m).
i) MMR data: S=3.4 (3H,s), 4.75 (2H,s), 5.g (lH,s),
ca. 7.3 (9H,m).
j) NMR data: ~=1.2 (3H,t), 3.55 (2H,q), 4.7 (2~,d),
5.95 (lH,broad), ca. 7.2 (8H,m).
X) NMR data: ~=3.35 (3H,s), 4.75 (2H,s1, 5.9 (lH,s,broad),
ca. 7.2 (9H,m)
1) ~MR data^ ~=2.3 (6H,s), 3.3 (3H,s), 4.75 (2H,s)
5.9 (lH,s,broad), 7.0-7.4 (8H,m).
m) NMR data: ~=3.4 (3H,s), 4.75 (2H,s), 5.9 (lH,s,broad),
ca. 6.8-7~3 (8H,m)
,,.,~
/
23
In another aspect the invention provid~s a process of
inhibiting the growth of unwanted plants, which comprises
applying to the plants, or to the locus thereof, a phyto-
toxic amount of a compound of the formula (I) as
hereinb~fore defined. The amount of the compound may vary,
depending upon the identity of the particular compound
chosen and the plant species whose growth i5 to be
inhibited, but in general a~ounts of from 0.01 to 5.0
kilograms per hectare will be suitable: usually the amount
will be from 0.2 to 1.O kilograms per hectare. The skilled
worker in the herbicide art will readily be able to
establish ~ppropriate application rates by standard
procedures without undue experimentation.
The compounds of the invention are xelatively less
toxlc towards certain crop plants than they are towards
other plant species; accordingly, there is the possibility
of using the compounds for selective weed control in these
crops. Examples of such crops include cvtton, sugar beet,
rape, lettuce, peas; the compounds may be useful in a
number of crops of tl-e families Compositae and
Leguminosae.
The compounds used in the process of the invention are
preferably applied in the form of a composi~ion, in which
the active ingredient is mixed with a carrier comprising a
solid or liquid diluent. In another aspect, therefore, the
invention provides a herbicidal composition, comprising as
an active ingredient a compound of the formula (I) as
hereinbefore defined, in admixture with a solid or liquid
diluent. Preferably the composition also comprises a
surface-active agent.
The solid compositions of the invention may be for
example, in the ~orm of dusting powders, or may take the
form of granules. Suitable solid diluents include, for
example, kaolin, bentonite, kieselguhr, dolomite, calcium
carbonate, talc, powdered magnesia, and Fuller's Earth.
X
24 ~ 3.~
Solid cornposltions ~ay also be in the form of
dispersible powders or grains comprising in additlon to
the active ingredient, a wetting agent to facilitate the
dispersion of the powder or grains in llquids. Such
powders or ~rains may include fillers, suspending agents
and the like.
Liquid compositions include aqueous solutions,
dispersions and emulsions containing the active ingredient
preferably in the presence of one or more surface active
agents. ~1ater or organic liquids may be used to prepare
~olutions, dispersions, or emulsions ~f the active
ingredient. The liquid composition~ o the ~nventio~ may
also contain one or more corrosion inhibitors for example
lauryl isoquinoliniwm bromide.
Sur~ace active agents may be of the cationic, anionic
or non-ionic type. Suitable agents of the cationic type
include for example quaternary a~monium compounds, for
example cetyltrimethyl ammonium bromide. Suitable agents
of the anionic type~nclude for example soaps, salts of
aliphatic mono-esters of ~ulphurlc acid, for example
sodium lauryl sulphate: and salts of sulphonated aromatic
compounds, for example dodecyl~enzenesulphonate, sodium,
calcium and ammonium lignosulphonate, butylnaphthalene
sulphonate, and a m~xture of the sodium salts of diiso-
propyl- and triisopropyl-naphthalenesulphonic acid.
Suitable agents of the non-ionic type include, for
example, the condensation products of ethylene oxida with
fatty alcohols SUCll as oleyl alcohol and cetyl alcohol, or
with al~yl pllenols 3uch as octyl-phenol, nonylphenol, and
octylcresol. Other non-ionic agents arc the partial esters
derived from long chain fatty acids and hexitol
anhydrides, for example sorbitol monolaurate the
condensation products of the said partial esters witn
ethylene oxide and the lecithins-
2 S ~ h ~
The co~positions which are to be used in the form ofaqueous solutions, dispersions or e~uls~ons are generally
supplied in the for~ of a concentrate contalnin~ a h~gh
proportion of the act~ve ingredient, the concentrate being
diluted with water before use. These concentrates are
usually required to with3tana storage for prolonged
periods and ater such stora~e to be capable of dilution
with water in order to form aqueous preparatlons whlch
remain homogenous for a sufficient time to enable them to
be applied by conventional spray equip~ent.
The compositions of the lnvent~on may contain, in
addition to carriers and surfac~-actlve agents, variou~
other constituents to increa~e their u~efulness. They may
contain~ for example, buffer~ng salt~ to maintain the pH
of the co~position with~n a aesired range: antlfreeze
agents, for example urea or propylene glycol: adjuvants,
for example oils and humectants: ana sequestrants, for
example citric acid and ethylenediam~netetracetic acid,
which help to pre~ent the formatlon of insoluble
precipitates when th~ co~po~itions are diluted with hard
water. Aqueous dispersion~ may conta~n anti-settling
agents and anti-caking agent~. The composi;tion~ may in
general contain a dye or pigment to impart a
characteristic colour. Agents for increa~ing viscosity may
2S be added to reduce the for~ation of fine droplet~ during
spraying, and thereby reduce spray drift. Other additives
useful for particular purposes will be known t~ those
skilled in the formulation art.
In general concentrates may conveniently contain from
30 10 to 85% and preferably fro~ 25 to 60% by weight of
active ingredient. Dilute preparations ready for use ~ay
contain varying amounts of the active ingredient,
depending upon the purpose for which they are to be used;
however, dilute preparations suitable for ~any uses
35 contain between 0.01~ and 10~ and preferably between 0.1
and 1~ by weisht of the active ingredient.
~!
2G ~.~3;~
The invention Eurt71er ~rov~des Frocess~s ~or prepar~ng
compo~n~s oE Eormula ~I) above. Thus~ compounds ~Iherein
R2 ~5 hyclrogen may be prepared, for example, by the
proces~ of Scheme A below ~-
Scheme A
(a) Rlcocl + NH2CH2CN --~ RlCoNHc~2c~T
~r
(b3 (III) ~ brominating ag~nt ~ RlCONHC~CO~IH2
(IY~
XR3
(c) ~IV) ~ ~3XH , ~ RlCONHCH
\ CO~t2
~V)
(d) (V~ + dehydrating agent > RlCl~N~I--CII
\
CN
tVI)
. ;.
. ~ ~
~ ~3;~
The process outlined in Scheme ~ begins with step (a),
in whicll an acid chloride Rlcocl is reacted with amino-
acetonitrile by a convent~onal procedure to obtain the
acylamir,oacetonitrile der~vative (III). Thi3 is then
reacted in step (b) w~th a brominating agent (for example
bromine in glacial acetic acid) t~ gi~e the brominated
derivative (IV). This brom1nation procedure also
simultaneously hydrates the cyano group to a carbamoyl
group -CONH2, and necessitates treatment with a
dehydrating agent at a later stage to convert the
carbamoyl group back into a cyano groupO It may be
possible to avoid the undes;red converslon of the cyano
group to carbamoyl by uYe of a different solvent or
brominating agent and thereby shorten the process by
mak~ng step (d) unnecessary.
In step (c), the bromo compound (IV3 i8 reacted with
an appropriate alcvhol, th~ol, or amlde of formula R3XH
to obtain the carbamoyl compound (V). Preferably the
reaction i5 carried out in a solvent; the solvent should
be an aprotic solvent to avoid reaction of the solvent
with the bromo-compound (IV). Preferably an acid acceptor
i8 present in at least a 3toichiometric proportion.
Examples of acid acceptors include tertiary amines, for
example triethylamine and pyr~dine. The reaction takes
place readily even at ambient temperatures but may be
accelerated if deRired by heating for example to lOO~C or
above.
The intermediate compounds of formula IV and V are
novel and constitute a further aspect of the present
invention.
~ le final step (d) of Scheme ~ is the treatment of the
carbamoyl compound (V) with a dehydrating agent to convert
it to the corresponding cyano compound. The dehydrating
agent may be, for example, a bi-molar amount of p-toluene
3S sulphonyl chloride in pyridine as solvent and acid
acceptor, or another dehydrating agent, for example
2~
phosphorus o~ychloride-climethylformamide. The reac~ion
with p-toluenesulphonyl chloride proceeds readily at
ambient temperature. Scheme A has been described in
terms of brominated compounds; however, the scheme could
equally he carried out using a chlorinating agent (e.g.
gaseous chlorine) in place of a brominating agent, to
produce the chlorinated compound corresponding to compound
(IV), this could then be used in step (c) in place of
compound (IV). This rou~e cannot be used where Rl is
readily attacked by elemental bromine or chlorine.
A further process for making compounds of the
invention in which R2 is hydrogen is ou~lined in Scheme
B :-
Scheme B
(a) RlCONH2 + HCO-C02R6-~ RlCONH-CH(OH)C02R6
(VII)
(b) (VII) + SOC12~ RlcONHcH(cl~c02R6
(VIII)
/ XR3
(c) (VIII) + R3XH - -~ RlCONHCH
\ CO2R6 (R3)
(IX)
(d) (IX) + ~3 ~ (V)
29 1 ~3~R~
In step (a) of Scheme B, an amide RlCONH2 is
condensed with a glyoxylic ester HCO-C02R6 to give the
hydroxy intermediate (VII). The group R6 is an ester
radical, for example an alkyl group of 1 to 4 carbon atoms
(e.g. a methyl group). In step (b), the hydroxy
intermediate (VII) is treated with a chlorinatina aaent
(e.g. thionyl chloride) to convert it to the chloro-
derivative (VIII). This is in turn reacted in step (c)
with the appropriate alcohol, thiol, or amine R3XH to
give the ester (IX)o Treatment of this with ammonia in
step (c) gives the carbamoyl derivative (V) which may then
be converted to the cyano compound of the invention by the
method of step (d) of Scheme A.
An alternative process for preparing the amide
derivatives of the invention when X=0 in formula I is a
variation of the Scheme B process above. This Scheme B
variation is outlined below :
OH
(a) RlCONH2 ~ HCOCOOR6__~ RlCONH~CHCOOR6
(VII)
OH
(b) RlCONH-CHCOOR6
(VII) ~ HXR3
¦ (H2S04 present as
/ catalyst)
X~3
~G//
RlCONHCH
\ (IX)
COOR6
XR3 XR3
(c) RlCONHCH + NH3~ RlCONHCH
\ COOR6 COMH2
(V)
) NH3
R3
RlCONHCH
CN
(VI)
In this modified Scheme B procedure it can be seen
that one can proceed directl~r from the hydroxy
intermediate (VII) to the ester (IX~ in one step. The
ester ~IX) is then treated with ammonia, as in step d, to
S produce the carbamoyl derivative ~V) which in turn is
converted to the cyano compound of the Invention (VI) by
means of the final step ~step d) of the process of Scheme
A.
i
,,// , .
~ ~ ................. _ ,
.
31 ~33~
A further process for preparirlg compounds of the
invention in which the group XR3 is an -N~-COZ group
where Z is an alkyl or alkylene radical is outlined
in Scheme C below.
Scheme C
. . ~
NHCOZ
(a) RlCONHCH(Br)CONH2 ~ ZCN AcetiC Rl~ON~CH
acid,
H2SO4 CQNH2
(IV) (X)
/ NHCOZ
(b~ (X) dehydrating ~ Rl- CONHCH
agent
CN
(XI)
According to Scheme C the bromo-amide (IV) (prepared
as in Scheme A) is reacted with the appropriate nitrile
ZCN in acetic acid under the conditions of the Ritter
reaction to give the amide (X). This is then treated with
a dehydrating agent (e.g. trifluoroacetic anhydride in
pyridine) to give the requirecl nitrile (XI).
A further method of preparing the nitriles (XI) is
shown in Scheme D below .
3~
32
Scheme D
OH NHCO~
.
(a) RlCONHCH ~ ZCN acet~c aCidJRlCONHCH
\ H2SO4
C02R6 C02R6
(VII) (XII)
(b) ~XII) ~ NH3 - ~ (X) dehydrating~ (XI)
agent
.
In Scheme D~ the hydroxy-ester (VII) prepared as in
Scheme B is reacted with the appropriate nitrile ZCN in
the pre~ence of acetic acid and sulphuric acid (Ritter
reaction~ to give the amide (XII). This may then be
reacted with ammonia to give the amide (X) already
prepared in Scheme C. As in Scheme C the amide ~X) may
then be dehydrated to give the required nitrile (XI). The
conversion of (XII) to (X) may be troublesome because the
esters (XII) tend to be highly insoluble.
A further method of preparing compounds of the
invention is outlined in Scheme E.
Scheme E
-
XR3
(a) RlCONHR2 (i)NaH RlCON -CH
(ii)R3X~CH~Br)C02R6
R2 C02R6
~XIII)
.. .
~3~
33
XR3
(b) (XIII) + NH3 . ~ RlCON CH
12 \
R CONH2
(XIV)
XR3
(c) (XIV) ~ d ~ RlCO~ - CH
agent 12
R CN
~XV)
According to Scheme E, an amide RlCONHR2 i5 first
treated with sod ium hydride and the an~on so generated is
then reacted with an alpha bromo ester R3X-CH~Br)CO2R6
to give the ester (XIII). Thi5 is then reacted with ammonia
to give the amide (XIV), and finally (XIV~ is treated with
a dehydrating agent to give the ni~rile (XV).
Thi8 method may ~onveniently be used to prepare
compound6 in which R2 is other than hydrogen,
particularly when either Rl or R2 is susceptible to
reaction with bromine or sulphuryl chloride, which are used
as reagents in certain other routes described herein.
A further method for preparing compounds of the
invention is outlined in Scheme F.
Scheme F
(a~ R2NH2 + HOCH2CN ~ R2NHCH2CN
(b) R2NHCH2CN + RlCOCl------~ RlCONCH2CN
¦ (XVI~
R2
'X!
3~
(c) (XVI) + 502C12 ~ CON- Cil
(or Br2~ L 12 \ C~
(XVII)
XR3
(d) (XVII) + HX~ _ ~ RlCOUCH
Base ¦ \
12 \
R CN
(XV)
According to Scheme F, an amine R2NH2 is condensed
with formaldehyde cyanhydrin to give the substituted amino-
acetonitrile R2NHCH2CN. This is then acylated by theappropriate acid chloride RlCOCl tc, give the amide
derivative (XVI).
This in turn is chlorina~ed ~e.g. with 502C12) or
brominated (e.g. with Br2) to give the highly reactive
bromo- or chloro-derivative (XVII~. This is treated with
the appropriate alcohol, thiol or amlde ~3XH in the
presence of base to give the required nitrile (XV).
T~le chloro- or hromo- nitriles (XVII) are too unstable
to be isolated and characterised, and are used within a
sllort time after they are prepared. The final stage (d) of
the scheme may conveniently be carried out by using an
excess of the alcohol, thiol, or amide ~3XH as solvent,
and anhydrous potassium carbonate as the base.
Triethylamine or other tertiary amines may also be used as
the base.
~1 ~3~
The cyanoamides (XVI~ may also be prepared by methods
other than that described above. Thu9, the R2 substituent
may be introduced by alkylation as ~hown below :-
RlCONHCH2CN (i) N~ RlCONCH2CN (XVI)
~ R Br
R2
Another alternative is shown below :-
RlCoNHR2 (i) NaH RlCONCH CN (XVI)
( i i ) ClCH2CN
R2
Compounds of the invention in which the group E i8 a
thiocarbamoyl radical may be prepared according to Scheme Gbelow :-
Scheme G
XR3 XR3
RlCON--CH H2S ~ RlCON__CH
¦ ~ Pyridine/Et3N 1~ \
R2 R CNH2
(XVIII)
The reaction is conveniently carried out by passinggaseous H2S through a solution of the nitrile in pyridine
containing a little triethylamine as catalyst. Usually the
solution is externally cooled to 0-10. If the product does
not separate from the solution, it may be isolated by
removal of the solvent.
B~4
36
The amide derivatives of formula I, and compositions
containing them, are variously active against a wide range
of fungal diseases, particularly, for example, against:
Plasmopara viticola (downy mildew) on vines and
Phytophthora infestans (late blight) on pot~toes and
tomatoes and other species of Phytophthora
Phytophthora parasitica, Phytophthora cinnamomi,
Phytophthora ~ and Phyto~hthora capsici on a
range of commercially important crops
Peronospora tabacina on tobacco
Peronospora para~itica on cabbage
Peronospora destructor on onions
Bremia lactuca on lettuce
Pythium specie~ on a range of commercially importan~
crops
Other fungal di~eases, for example:
Venturia inaequalis (scab) on apples
Cercospora arachidicola on peanuts and other
Cercospora species.
A particularly valuable feature of the activity of the
amide derivatives i8 their systemic effect, i.e. their
ability to move in a plant to combat an infection or
infestation remote from the site of initial application.
Thus a derivative, or a composition containing it, may be
applied to the soil surrounding the roots of a plant or to
the seed or to other plant area~, e.g. leave~, and be taken
up by the plant through Its roots, or other areas, to
combat fungi locelly or elnewher~ _
// '
/
37
In another aspect, therefore, the invention provides a
process for combatt-ing fungi, especially of inhibiting the
growth of fungi on plants, which comprises applying to the
plant~, or the locus thereof, a fun~icidally effective
amount of a compound of the formula (I) as hereinbefore
defined. The amount of the compound may vary, depending
upon the identity of the particular compound chosen, the
fungal species whose growth is to be inhibited, and the
plant or locus involved.
The skilled worker in the fungicide art will readily be
able to establish appropriate application rates by
standard proeedure~ without undue experimentation.
Preferred compounds for use in the fungicidal
compositions of the invention and the process for
combatting fungi are those defined in detail above with
reference to formula I wherein R2 i9 hydrogen, Rl is
optionally-substituted phenyl, or heterocyclyl, for example
2-furyl, X is 0 or S (X is preferably 0) and R3 is
alkyl, alkenyl, or haloalkyl, and E is CN or CSNH2.
Preferred phenyl substitution, when Rl is phenyl, is
at the 3, 4 or 5 positions and is alkyl, alkoxy,
methylenedioxy or halogen. Preferred alkyl groups for R3
are Cl_4 alkyl. Allyl is also a preferred group for R3.
The compounds used in the process and compositions of
the invention are preferably applied in the form of a
composition, in which the active ingredient is mixed with a
carrier comprising a solid or liquid diluent. In another
aspect, therefore, the invention provides a fungicidal
composition, comprising as an active ingredient a compound
of the formula (I) as hereinbefore defined, in admixture
with a solid or liquid diluent. Preferably the composition
also comprises a surface-actlve agent. ~
-
~,
3~
The amide derivatives l~ay ~)e used as such for anti-
fungal purposes but are more conveniently formulated into
compositions for such usage.
The invention also provides fungicidal compositions
S comprising as active ingredient an amide derivative as
defined in any of the paragraphs above.
The amide derivatives and compositions containing them
can be used to combat plant fungi and treat plants or seeds
in a number of ways, for example -they can be applied,
formulated or unformulated, directly to the foliage of a
plant which is infected or likely to become infected, or
they can be applied also to bushes and trees, to soil or to
other medium in which plants, bushes or trees are growing
or to ba planted, or they can be sprayed on, dusted on or
applied as a cream or paste formulation. Application can
be to any part of the plant, bush or tree, for example to
the foliage, stems, branches, seeds or roots, or to the
soil surrounding the roots.
The terms "combatting" and "treatment" as used
herein embrace all the foregoing modes of ap~lication and
the term "plant" includes seedlings, bushes and trees.
Furthermore, the method of the invention includes
protectant, prophylactic and eradicant treatment.
The derivatives are preferably used for agricultural
and horticultural purposes in the form of compositions.
The type of composition used in any instance will depend
upon the particular purpose envisaged.
The compositions may be in the form of dustlng powders
or granules, for example ordinary grains or "slow release"
granules wherein the active ingredient is mixed with a
solid diluent or carrier, for example, kaolin, bentonite,
kieselguhr, dolomite, calcium carbondte, talc, powdered
magnesia, Fuller's earth, gypsum, Hewitt's earth,
diatomaceous earth and China clay.
39
Compositions Eor dressing seed ~ay, f~r example, comprise
an agent (for example a mineral oil) for assisting the
adhesion of the co~positlon to the seed.
The compositions may also be in the for~ of
S dispersible powders or grains comprising a wetting agent to
facilitate the dispersion in liquids af the powder or
grains which may contain also fillers and suspending
agents.
The aqueous dispersion of emulsions may be prepared by
dissolving the active ingredient~s~ in an orqanic solvent
which may contain wetting, dispersina or emulsifying
agent(s) and then addlng the mixture so obtained to water
which may also contain wetting, dispersing or em~lsifying
agent~s). Suitable organic solvents are ethylene
dichloride, isopropyl alcohol, propylene glycol, diacetone
alcohol, toluene, kerosene, methylnaphthalene, xylenes and
trichloroethylene.
The compositions for spraying may also be in the form
of aerosols wherein the formulation is held in a
propellant, e.g. fluorotrichloromethane or dichloro-
difluoromethane.
By including suitable additives, for exa~ple additives
for irnproving the distribution, adhesive power and
resistance to rain on treated surfaces, the different
cornpositions can be better adapted for various uti-lities.
The derivatives can be used in smoke generators and
also as mixtures with fertilisers (e.g. nitrogen- or
phosphorus- containing fertilisers). Compositions
comprising only granules oE fertiliser incorporating, for
example coated with, the derivative, are preferred.
The invention therefore also provides a fertiliser
cornDosition comprising the derivative and a fertiliser.
The compositions mav also be in the form of liquid
preparations for use as dips or sprays which are generally
aqueous dispersions or emulsions containing the active
ingredient in the presence of one or more surface
" ~a~3;3~2,~
active agent(s), dispersing agent(s), emulsifying agent(s)
or anionic or non-ionic agents. Suitable cationic aaents
are quaternary ammonium compounds for example,
cetyltrimethylammonium bromide.
Suitable anionic agents are soaps, salts of aliphatic
monoesters of sulphuric acid (for example sodium lauryl
sulphate), and salts of sulphonated aromatic compounds (for
example sodium dodecylbenzene-sulphonate, sodium, calcium
or ammonium lignosulphonate, butylnaphthalene ~ulphonate,
and a mixture of sodium di-isopropyl- and
triisopropylnaphthalene sulphonates).
Suitable non-ionic agents are the condensation
products of ethylene oxide with fatty alcohol~ such as
oleyl alcohol or cetyl alcohol, or with alkyl phenols such
as octylphenol, nonylphenol and octylcresol. Other non-
ionic agents are the partial esters derived from lony chain
fatty acids and hexitol anhydrides, the condensation
products of the said partial esters with ethylene ocide,
and the lecithins. Suitable suspending agents are
hydrophilic colloids (for example polyvinylpyrrolidone and
sodium carboxymethylcellulose), and the vegetable gums ~for
example gum acacia and gum tragacanth).
The compositions for use as aqueous dispersions or
emulsions are generally supplied in the form of a
concentrate containing a high proportion of the active
ingredient(s), the concentrate to ~e diluted with water
before use. These concentrates often should be able to
withstand storage for prolonged periods and after such form
aqueous preparations which remain homogenous for a
sufficient time to enable them to be applied by
conventional spray equipment. T~le concentrates may
conveniently contain 10-85%, generally 25-60~, by weight of
the active ingredient(s).
~7hen diluted to form aaueous preparations, such
preparations may contain varying amounts of the active
ingredient(s) depending upon the intended purpose, but an
aqueous preparation containing 0.0005% or 0.01~ to 10~ by
weight of active insredient(s) may be used.
4 ~
The co~positions of this invention can co~prise also
other compound( 5 ) having bioloyical activity, e.g.
compounds having similar or complemen~axy fungicidal or
plant growth regulating activity or compounds ha~ing
herbicidal or insecticidal activity.
The other fungicidal co~pound can be for example one
which is capable o combating ear diseases of cereals (e.g.
wheat) such as Septoria, Gibberella and Relminthosporium
spp., seed and soil borne di.seases and downy and powdery
~ildews on grapes and powdery mildew and scab on apple etc.
These mixtures of fungicides can have a broader spectrum of
activity than the compound of general formula II) alone;
furt~er the other fungicide can have a synergistic effect
of the fungicidal actiYity of the compound of general
lS formula (I). Examples of the other fungicidal compound are
imazalil, benomyl, carbendazim (BCM), thiophanate-methyl,
captafol, captan, sulphur, dithiocarbamates, carbathiins,
copper oxychloride, triforine, dodemorph, tridemorph,
dithianon, pyrazophos, binapacryl, quinomethionate,
panoctine, furalaxyl, aluminium tris(ethylphosphonate~,
DPX3217* ethirimol, dimethirimol, b~pirimate,
chlorothalonil and metazanine.
Suitable insecticides are pirimorS croneton,
dimethoate, metasystox and formothion.
The other plant growth regulating compound can be one
which controls weeds or seedhead for~ation, improves the
level or longevity of the plant growth resulating activity
of the compounds of general formula ~I), selectively
controls the growth of the less desirable plants (e.g.
grasqes) or causes the compound of general for~ula (I) to
act faster or slower as a plant growth reaulating agent.
Some of these other agents wîll be herbicides. Examples of
suitable agents are the gibberellins (e.g. GA3, GA4 or
GA7), the auxins (e.g. indoleacetic acid, indolebutyric
acid, naphthoxyacetic acid or naphthylacetic acid), the
cytokinins (e.g. kinetin, diphenylurea, benzimidazole,
benzyladenine or BAP), phenoxyacetic acids (e.g. 2,4-D or
~Reg Trade Mark
,
4~. 3L~3~3~
MCPA), substituted benzoic acids (e.g. TIBA~, morphactins
(e.g. chlorfluorecol), maleic hydrazide, glyphosate,
glyphosine, long chain fatty alcohols and acids (e.g. Off
Shoot O*or Off Shoot ~ , dikegulac, Sustar* Embark*
substituted quaternary ammonium and phosphonium compounds
(e.g. CC~ or Phosfon-D~, Ethrel, carbetamide, Racuza, Alar,
asulam, abscissic acid, isopyrimol, RH531~, hydroxy-
benzonitriles (e.g. bromokynil), Avenge, Sufix or Lontrel.
Th~ invention is illustrated by the following Examples,
in which unless otherwise stated all parts are by weight
and temperatures in dPgrees Centigrade. The Examples that
describechemical syntheses give details in some cases o
the nuclear magnetic resonance ~NMR) spectra of the
compound~. The information given is the chemical shift (S)
for each peak in the spectrum together with a symbol to
indicate the nature of the peak, as follows :- s(singlet);
d(doublet); m(multiplet); c(quartet) J t(triplet). The
solvent used was fully deuterated dimethyl sulphoxide or
deuterochloroform (CDC13).
EXAMPLE
.
This Example illustrates the preparation of com~pound
no.4 of Table I by the process of Scheme A.
(a) Preparation of Benzoylamino(bromo)acetamide
To a suspension of benzoylaminoacetonitrile (5 g) in
stirred glacial acetic acid (50 ml) was added all at once
bromine (5.0 9). After a brief induction period, the
bromine colour was discharged and the product (5.8 g)
precipitated from the acetic acid. The product was filtered
off, washed with glacial acetic acid, and then with
~ anhydrous ether, and dried. A sample crystallised from
~lacial acetic acid had m.p. 157 (dec.).
... .~.
43
8,.."4
Found: C, 42.22; H, 3.7; N, 10.81 CgHgBrN202
reauires : C, 42.02; H, 3.5, N, 10.89~.
~b) Preparation of Benzoylamino~ethoxy)acetamide
The foregoing bromoamide (13.4 g) was suspended in
anhydrous ethanol (50 ml) and heated on a steam bath just
long enough for it to dissolve (ca. 5 min), whereupon the
solution was cooled. 'Fhe ethanol was removed under vacuum
and the residual heavy oil was dissolved in water (40 ml)
and neutralised by the cautious addition of solid sodium
bicarbonate. 'Fhe solution was then extracted with chloro-
form (200 ml) and the dried (~IgS04) extract evaporated to
yield a white solid. Crystallisation of this from dichloro-
methane-hexane gave the product (7.7 g), m.p. 148-150.
Found: C, 59.19; H, 6.27; N, 12.5 CllH14M203
requires : C, S9.45; H, 6.34; N, 12.6% ~(DMS0 d6): 1.15
(t, 3H), 3.55 (q, 2H), 5.55 (d, lH), 7.2~8.0 (m, 7H~, 9.0
(d, lH).
(c) Preparation of Benzoylamino(ethoxy)acetonitrile
(Compound No. 4)
A solution of the foregoing ethoxyamide (5.55 g) in
anhydrous pyridine (40 ml) containing p-toluenesulphonyl
chloride (4.78 g) was kept at room temperature for 72
hours. The reaction mixture was diluted with water (200
ml) and the precipitated solid filtered off, washed with
water and dried. Crystallisation of the soli~ from carbon
tetracnloride gave the product (2.5 g), m.p. 107-llG.
Found: C, 64.31, H, 6.3, N, 13.54 CllH12
4 'I o.~ ~3~
requires : C, 64.69; H, 5.92; N, 13.71~ S(C~CL3): 1.25
~t, 3H), 3.8 (q, 2H), 6.3 (d, lH), 7~a-8.0 (m, 6H).
EXP~IPLE 2
This Example illustrates the preparation of compound
no.38 of Table I by the process of Scheme B.
(a~
~hydroxy)] acetate
3-Methoxybenzamide (13.25 g) and methyl glyoxylate (7.72
g) in toluene ~150 ml) were heated under reflux in a ~ean-
Stark apparatus for 6 hours. On cooling the mixture the
product separated and was crystallised from toluene.
Yield, 12.0 g, m.p. 93-94.
Found: C, 55.45, H, 5.37 N, 6.3 CllH13~O5
requires : C, 55.23; H, 5.43; N, 5.85~.
(b) Preparation of ~-Methoxybenzoylamino(ethoxy)acetamide
The foregoing ester (5.0 g) and thionyl chloride (40 ml)
were stirred together for 2 hours., after which the excess
of thionyl chloride was removed under vacuum. The residue
was dissolved in ethanol (100 ml) and the solution .hen
ev~porated under vacuum. The residual oil was treated wiLh
aqueous ammonia (d 0.88) and the mixture allowed to stand.
The solid so formed was filtered off, dried, and
crystallised from chloroform-light petroleum to give the
product (1.8 g), m.p. 143-144.
round: C, 56.17; H, 6.49; ~`7~ 10.73 C12~16N2 4
,~5 ~L~23~
requires : C, 57.14, H, 6.35; N, 11.11% S(~MSo-d6):
1.3 (t, 3~), 3.7 (q, 2H), 4.0 (s, 3H), 5.7(d,1H), 7.2-7.8
(m, 6H), 9.15 (d, 1~).
(c) Preparation of 3-Methoxybenzoylamino(ethoxy)
acetonitrile
The foregoing ethoxyamide ~1.0 g), p-toluenesulphonyl
chlorlde (1.28 g) and pyridine (20 ml) were allowed to
stand at room temperature or 72 hrs. The reaction was
then worked up as described in paragraph (c) of Example 1.
The product (0~7 g) was crystaliised from chloroform-
light petroleum and had m.p. 72.
~(CDC13) : 1.2 (t, 3H), 3.7 (q, 2H), 3.8 (s, 3H), 6.2
(d, lH), 7-7.6 (m, SH).
EXAMPLE 3
This Examp:Le illustrates the preparation of compound
no. 53 of Table 1, using the process of Scheme F.
Preparation of N-Methylbenzoylamino(methoxy)acetonitrile
,__.... .. .
To a cooled (5--10) and stirred solution of ~-methyl-
benzoylaminoacetonitrile (5.0 g) in anhydrous carbon
tetrachloride (75 ml) was added dropwise bromine (4.6 g).
Following the addltion the mixture was stirred for a
further 5 min. at room temperature, when methanol (2S ml)
was added all at once. After stirring the mixture for 2
further 5 min., triethylamine (5.81 g) was added to the
mixture. The solution was then washed with water and the
organic phase dried (MgS04) and evaporated. The residual
oil was chromatographed on a dry silica column usina
ether-hexane (7:3) as an eluen~. Separation o. the major
oand from the colu~n gave the product as a colourless oil
~1.0 g) n21 1.5233.
D
~6
123;~
~ (CDC13): 3.1 (s, 3H), 3.4 (s, 3H), 6.0 (very broad,
lH~, 7.4 (s, 5H).
EXAMPLE 4
_
This Example illustra~es the preparation of compound
no.40 of Table I, using the process of Scheme A.
(a) Preparation of 3-Chlorobenzoylamino(methylthio?-
acetamide
To a solution of 3-chlorob~nzoylamino(bromo)aceta~ide ~5.5
g) in anhydrous tetrahydrofuran ~100 ml) containing methyl
mercaptan (slight excess) W2S added 1 equivalent of
triethylamine and the mixture kept for 72 hrs. The
solution was filtered and the filtrate evaporated to give
an oll which solidified on treatment with ether.
Crystallisation of the solid from ethyl acetate gave the
product (0-67 g).
lS ~ (~MS0-d6): 2.06 (s, 3H), 5.6 (d, lH), 7.4-7.8 (m, 6H),
8.9 and 9.2 (two doublets, lH).
(b) Preparation of 3-chlorobenzoylamino(methylthio)-
acetonitrile (Compound No.40)
The foregoing amide (0.67 g) and 2 equivalents of p-
toluenesulphonyl chloride in pyridine (10 ml) were kept atroom temperature for 48 hrs. The mixture was then poured
into water (100 ml). The solid which separated was dried,
and crystallised from chloroform-light petroleum to give
the product (0.1 g), m.p. 115-117.
47
Found: C, 48.99; H, 3~71; N, 11.01 CloHgClN2OS
requires : C, 49.9; H, 3.77; N, 11.64~
5 (C~C13): 2.35 (s, 3H), 6.05 (d, lH~, 7.8-7.2 (m, 5H).
EXAMPLE 5
This Example illustrates the preparation of compound
no 158 of Table 1 by the process of Scheme C.
(a) Preparation of Acetylamino(3,5-dimethylbenzoylamino)
acetamide
To a suspension of 3,5-dimethylbenzoylaminoacetonitrile (1
g) in glacial a~etic acid (20 ml) was added all at once
bromine (0.85 g). After stirring the mixture at room
temperature for 15 min. the white solid was separated,
washed with anhydrous ether and then re-suspended in
glacial acetic acid (10 ml). To this was added
concentrated sulphuric acid (1.5 ml) and acetonitrile (8
ml). After 1 hour the mixture was poured intG water (30
ml) and extracted with chloroform (2 x 30 ml). The dried
(MgS043 extract was evaporated and the residue
crystallised frc)m aqueous ethanol to give the product
(Q.38 g) as a white solid (Compound No 154 of Table I),
20 m.p. 244-5 Q .
Found: C, 58.49, H, 6.42; M, 15.46 C13H17N3O3
requires : C, 59.13: H, 6.46; M, 15.g7%
~ (DMSO-d6): 1.9 (3H,s), 2.3 (6H,s), 5.8 (lH,dd), C2.
7.1-7.5 (5H,m), 8.3 (lH,d), 8.7 (lH,d).
(b) Preparation of Acetylamino (3,5-dime~hylbenzoylamino)
.
acetonltrile
The foregoing acetamide ( 1. O c ) w2s dissolved in anhydrous
~8
pyridine (25 ml) which was then cooled to -25.
Trifluoroacetic anhydride ~1.5 g) was added dropwise to
the cooled and stirred solution, and following the
addition the solution was allowed to come to 0 whereupon
it was poured into water (70 ml) and extracted with ether
(2 x 50 ml). Evaporation of the ethereal extracts and
crystallisation of the residue from ethyl acetate-hexane
gave the product (0.6 g) as a pale cream solid, mOp. 195-
7o.
Found: C, 62.51; H, 5.98; N, 17.16 C13H15N302
requires : C, 63.67; H, 6.12; N, 17.14%
~ (DMS0-d6) : 1.8 ~3H,s), 2.2 (6H,s), 6.2 (lH,dd~,
7.1 (l~,s), 7.4 (2H,s), 9.1 (lH,s), 9.5 (lH,s).
EXAMPL~ 6
This Example illustrates the preparation of compound
no.153 of Table I by ',he process of Scheme D.
(a) Preparation of Methyl Acetylamino (3,5-
dichlorobenzoylamino) acetate
.
A mixture of 3,5-dichlorobenzamide (19.0 g) and methyl
glyoxylate (8.8 g) in ethyl acetate (300 ml) was heated
under reflux for 8 hours. The solvent was removed and the
residual adduct was crystallised from chloroform-light
petroleum. A portion (4.0 g) of the adduct was dissolved
in a mixture of glacial acetic acid (30 ml) and
acetonitrile (10 ml) with stirring, and then concentrated
sulphuric acid (4 ml) was added. The mixture was kept at
room temperature overnight when water (100 ml) was added.
The precipitated solid was washed with water, dried, and
crystallised 'rom ethanol to give the product (2.45 g) as
a colourless crystalline solid, m.p. 235-237.
3 ~ L~
Found: C, 45.24; Il, 3-88, N, 8.84 C12H12C12N2O4
requires : C, 45.14; H, 3-76, N, 8.77~
S(~MSO-d6) : 1.95 13H,s), 3.7 (3H,s), 5-9 (lH,dd) t 7-95
(3H,m), 8.9 (lH,d), 9~75 (lH,d).
(b) Preparation of Acetvlamino (3,5~dichlorobenzoylamino)
acetamide
The foregoing ester (1.46 g~ was dissolved in
dimethylformamide (70 ml) which was then saturated with
ammonia (gas) and the mixture kept for 7 days. The solvent
was removed under reduced pressure and the residue
crystallised from aqueous dimethylformamide to give the
product (0~72 g), m.p. 267-268 (dec).
Found: C, 43.62; H, 3.72; N, 13.82 CllHllC12N303
requires : C, 43.42, H, 3.62; N, 13.82%
~ (~MSO-d6): 1.95 (3H,s), 5.9 (lH,dd), 7.3 (2H,d,broad)
7.6 (lH,m), 7.9 (2H,m), 8.35 (lH,d), 9.2 (lH,d).
(c) Preparation of Acetylamino (3,5-dichloroben~ovlamino)
acetonitrile
_
The foregoing acetamide (0.5 g~ in anhydrous pyridine (10
ml) at -25 was treated with trifluoroacetic anhydride as
described above. The product (0~18 g), crystallised from
aqueous dimethylformamide, had m.p. 227-228.
Found: C~ 45.95; H, 3.12; N, 14.43 Cl1HgC12N3O2
reauires : C, 46.15; H, 3.15; N, 14.68%
,~ ISO-d6): 1.95 (3H,s), 6.4 (lH,dd), 7.9 (3H,m), 9.35
(lH,d), 10.0 (lH,d).
5 (~ p ~ r~
EXA~PLE 7
This Example illustrates the preparation of compound
no.159 of Table I bv the process of Scheme E.
(a) N-Furfuryl-3,5-dichlorobenæamide
To a vigorously stirred solution of furfurylamine ~2.78 g)
in ethyl acetate (40 ml) was added sodium hydroxide (1.15
g) in water (45 ml), followed immediately by the addition
of a solution of 3,5-dichlorobenzoyl chloride (6.0 g) in
ethyl acetate (20 ml). Following the mild exothermic
reaction the ethyl acetate layer was removed, dried
(MgS04), and evaporated. Crystallisation of the residue
from cyclohexane gave the product ~6.6 g) as colourless
needles.
(b) Preparation of N-Furfurvl-3,5-dichlorobenzoylamino
~ , . , _ _
(methoxy) acetonitrile
To a stirred suspension of sodium hydride (0.58 g) in
anhydrous tetrahydrofuran (40 ml) was added in portions
the foregoing a~ide (3.0 g). Following the addition and
cessation of hydrogen evolution was added with stirring
methyl 2-bromo-2-methoxy acetate (2.04 g) and the mixture
stirred for a further 2 hours at room temperature. Water
(100 ml) was then acded and the solution extracted with
methylene chloride (3 x 50 ml) and the extracts dried and
evaporated. The resultant crude oily ester was dissolved
in methanol (20 ml) which was then saturated with ammonia
gas and kept overnight. The solvent was removed under
reduced pressure and the residual oil triturated with
ether to give crude amide (1.91 g). The crude amide (1.75
g) was dissolved in anhvdrous pyridine (10 ml), cooled to
51 1~3~3~4
0~ with stirring and phosphorus oxychloride ~0.84 g) added
dropwise so that the temperature of the mixture did not
exceed 0. After 25 minu~es at 0, water (100 ml) was
added and the mixture was extracted with ether (40 ml).
The dried (MgS04) ether extract was chromatographed on
silica using diisopropyl ether as the eluent. Following
elution from the column and evaporation of th~ solvent the
product (1.24 g) was obtained as a colourless oil which
slowly crystallised, m.p. 89-90.
~ (CDC13): 3.4 (3H,s), 4.65 (2H,s), 6.1 (lH,s,broad)
6.3 (2H,m), 7.3-7.5 (4H,m).
~XAMPLE 8
This ~xample illustrates the preparation of compound
no.142 of Table I by the process of Scheme F.
Preparation of N-Benzyl-3,5-dimethylbenzoylamino(methoxy)
acetonitrile
To a stirred solution of glycollonitrile (25 g) in
methanol was added dropwise over 45 minutes benzylamine
(46.9 g) keeping the temperature of the reaction between
15-20. Following the addition the reaction mixture was
kept overnight at room temperature, and then distilled to
give benzylaminoacetonitrile (42.0 g) as a colourless oil,
b.p. 120/15 mm. Reaction of this (3.0 g) with 3,5-
dimethylbenzoyl chloride (3.46 g) as described above gave
crude N-benzyl-3,5-dimethylbenzovlaminoacetonitrile (5.81
g) as a colourless viscous oil which was used in the next
staae without further purification. To this crude amide
(2.0 g) in anhydrous methylene chloride (8 ml) was added
sulphuryl chloride (0.97 g). ~ollowing the cessation of
gas evolution (ca. 15 min.), anhyc-ous methanol (20 ml)
and finely powdered anhydrouc; potassi~l carborlate (1.95 g)
was added to ~he mixture which was then stirred for 30
minutes. Solids were removed from the solu-~ion which was
then evaporated and the residual oil chromatoaraphed on a
column of silica using methylene chloride as an eluent.
Following elution from the column and evaporation of the
solvent, the product (1.2 g) was obtained as a very pale-
yellow viscous oil.
Found~ C, 73.87, H, 6.67~ N, 9.22 ClgH20N202
requires : C, 74~Q2; H, 6.49, N, 9.09~
(CDC13j: 2~28 (6H,s), 3.25 [3H,s), 4.75 (2H,s), 5.85
(lH,s,broad), ca. 7.0-7.4 ~8H,m).
EXAMPLE 9
This E~ample illustrates the preparation of compound no.
84 of Table I ~y the process of Scheme C-.
Preparation of 3-chlorobenzovlamino(ethoxy)thioacetamide
Into a solution of 3- chlorobenzoylamino(ethoxy)
acetonitrile (1 g) in toluene (50 ml) containing
triethylamine (1 g) was passed hvdrogen sulphide gas. ~he
precipitated product (0.72 g) was collected and
crystallised from chloroform-light petroleum. m.p. 136-
137.
Found: C, 48.53; H, 4.8a; N, 10.19 CllHl~C1N202S
requires : C, 48.44; H, 4.80; N, 10.27%.
3 ~
EXA~PLE lO
This Example illustrates the herbicidal properties of
compounds of Table I. The compounds were submitted to
herbicide tests as described below.
~ach compound was formulated for test by mixing an
appropriate amount of it with 5 ml of an emulsion prepared
by diluting 160 ml of a solution containing 21.8 grams per
litre of Span 80 and 78.2 grams per litre of Tween 20 in
methylcyclohexanone to 500 ml with water. Span 80 is a
Trade Mark for a surface-active agent comprising sorbitan
monolaurate. Tween 20 is a Trade Mark for a surface-active
agent comprisina a condensate of 20 molar proportions of
ethylene oxide with sorbitan monolaurate. The mixture of
the compound and the emulsion was then shaken with glass
beads and diluted to 44 ml with water. The spray
composition so prepared was sprayed on to youna pot plants
(post-emergence test) of the species named in Tables 2 and
3 below, at a rate equivalent to lO00 litres er hectare.
~amaqe to plants was assessed 13 days after spraying by
comparison with untreated plants, on a scale of 0 to 5
where 0 is 0 to 20% damage and 5 is complete kill. In the
table of results, a dash (-) means no test was made.
A test was also carried out to detect pre-emergence
herbicidal activity. Seeds of the test species were placed-
on the surface of fibre trays of soil and were sprayed
with the compositions at the rate of lO00 litres per
hectare. The seeds were then covered with further soil. 20
days after spraying, the seedlings in the sprayed fibre
trays were compared with the seedlings in unsprayed
control trays, the damage being assessed on the sarne scale
Of 0 to 5-
The results of the tests are given in Tables 2 and 3
below.
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~-a~es of test plants in Ta~les 2 and 3
_ __ ___
Sb Suga.r beet
~ Rape
Ct Cotton
5 Sy Soya Bean
Mz Maize
~w llinter wheat
Rc Rice
Sn Senecio vulgaris
10 Ip Ipomoea purpurea
Am A~aranthus retroflexus
Pi Polygonum aviculare
Ca Chenopodium album
-
Po Portulaca oleracea
Xs and Xa Xanthiu~ spinosum
-
Ab Abutilon theophrastii
Cv Convolvulus arvensis
Ot/Av Oats tcultivated in pre-emergence test and
Avena fatua (wild oats) in post-emergence
test~ (Applies to Table 2; in Table 3 only
Avena fatua is used)
__
Dg Digitaria sanguinalis
Pu Poa annua
-
St Setaria viridis
25 Ec Echinochloa crus-galli
Sh Sorghum halepense
Ag Agropyron repens
Cn Cyperus rotund~s
Ga Galium aparine
30 Co Cassia obtusifolia
Al Alopecurus myosuroides
7 I
".X~E~L,E ll
This Exa~ple further illustra-tes the herbicid21
proper-ties of compo~lnds according to the in~ention. Tests
were carried out as clescriDed in Example 10, but using
different ranges of test plants. The pos.-emergence test
was slightly different from the one described in Exa~ple
10 in tha~ the seeds were sown in trays of soil and
covered with a few millimetres of soil before spraying the
test compound, whereas in the previous test the seeds were
sprayed directlyO
The compounds were formulated in a similar way to
that described in Example 10, but usina cyclohexanone
solution containing Synperonic NPE 1800*(a nonyl-phenol-
propylene oxide - ethylene oxide condensate~ and Tween 85*
~a condensate of sorbitan tri-oleate with 20 molar
~roportions of ethylene oxide~ instead of the
methylcyclohexanone solution of suxfac-tants described in
that Exa~ple. Tne da~age to the test plants was assessed
on a scale of 0 to 9 where 0 represents 0 to 10~ damase to
the plant and 9 is 90 to 100% damage. Assessments were
made 26 days after spraying the compounds. I~e results are
given in Tables 4 and 5 below. ~
"--
, .,
, ,,_
* Reg. 'l~rade Marks
-~ --- - -----
U~ ~D I ~ V
~:
G~ I` a~ o~
a~ ~* G~
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~ Z .
H
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~ 1 ~ ~ G C~ ~ ~ ~ ~ a~ ~ ~ ~ D~
P ~
_
O
H
~ U S ~ _l ~ ~ ~ ~ ~ ~ ~ ~ d~
~IX O ooooo ooooo
'_ . _
O O I ct~ ~
~ I ._. _ I
73
The na~es o~ the test plants in Table 4
~-lw ~inter wheat
Br Barley
Pe Peas
5 ~p Rape
Sb Sugar beet
Lt Lettuce
Av Avena fatua
Al Alopecurus myosuroides
10 Bt Bromus tectoru~
Ag Agropyron repens
Ga Galium aparine
S~ Stellaria edia
Ca Chenopodium album
15 Pi Polygonum viculare
Ma Matricaria inodora
Sp Sinapis alba /~'
~. ~
~ /
7 4
__ ~ _ __ _
C~ o o o o o
~ l l ~ U~
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~ ~ ~`
~ _. ~ o o
E~ X o ~ o ~ o
~ ~ ~ ~ ~ U~
~ 'u~ ~ ~ ~ ,1
~n ~ u~ ~ s~ c~
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.c ~ ~ ~ U~
E~ u:~ u~ ~ ~1 .
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V ~ ~ ~ ~
~r: r- o~ ~ ~ r
~: a~ r- o ~
,t o o o
D~ _
3 __
G Z 1~ _ ~ O N
3~
The names of test ~lants in Table_5
.
Mz Maize
Rc Rice
Sy Soya bean
Ct Cotton
To Tomato
Sg Sorghum
Eh Euphorbia heterophylla
Ip Ipomoea purpurea
10 Ab Abutilon theophrasti
Se Sesbania xaltata
Si Sida spinosa
Ds Datura stramonium
Xa Xanthium pensylvanicum
15 Ec Echinochloa crus-galli
Dg Digitaria sanguinalis
St Setaria viridis
Sh Sorghum hale~ense
Pm Panicum maximum
20 Cd Cyperus difformis
Cn Cyperus rotunius
,
, .
76
~f~
EXAMPI.E 12
This Example ill~strates a composltion according to
the invention w~ich comprises an e~ulsifiable concentrate.
The following ingredients were thoroushly mixed to give a
solution.
Compound No. 2 of Table I10%
Ethylene dichloride 40
Calcium dodecylbenzenesulphate 5~
"Lubrol" L 10%
"Aromasol" H 35%
EXP~PLE 13
A composition in the form of grains readily
dispersible in a liquid, e.g. water, was prepared by
grinding together the first three ingredients in the
presence of added water and then mixing in the sodiu~
acetate. The resultant mixture ~as dried and passed
through a British Standard r,~esh sieve, size 44-100, to
obtain the desired size of grains.
Compound Mo. 4 of Table I 50
"Dispersol" T 25~
"Lubrol" APN 5 1.5%
Sodium acetate 23.5
EXAI1PLE 14
The following ingredients were ground together
to produce a powder formulation readily dispersi~le in
liquids.
;:L~ 2~
CO~pour~ o. ~ of r~ T ~5Q
"Dispersol" T 5~,
"L.issapol" NX * 0-5%
"Cellofas" B600 2
Sodium acetate 47.5%
EXAMPLE 15
~ he active ingredient was dissolved in acetone and
the resultant liquid was sprayed on to the granules of
china clay, The solvent was then allowed to evaporate to
produce a granular composi~ion.
Compound No.18 of Table I 5%
China clay granules 95
EXAMPLE 16
A composition suitable for use as a seed dressing was
prepared by mi~ing the following three ingredients.
Compound No.2 of Table I 50%
Mineral oil ~%
China clay 48%
E~1PLE 17
A dusting powder was prepared by mi~ing the active
ingredient with -talc.
Compound No. ~ of Table I 5
Talc 95
* Reg. Trade Mark
~8 ~. R,~
~ Pr-r~ l~
A CoL formulation was prepared by b.~ r~illinc3 the
constituents set out below and then for~ing an aqueous
suspension OL the ground mixture with ~Jater.
Compound No. 8 of Table I 40%
"Dispersol" T 10%
"Lubrol" APN5 1~
Water 49%
EXAMPLE 19
A dispersible powder for~ulation was made by mixing
tosether the ingredients set out below and then grinding
the r~ix,ure until all were thoroughly mixed.
Co~pound No. 18 of Table I 25%
"Aerosol" OT/B* 2
"Dispersol" A~C. 5
China clay 28
Silica 40Q
EXAMPLE 20
This Example illustrates the prepara-tiorl of a
dispersible po~der formulation. The ingredients ~ere
~ixed and the mixture then ground in a comminution ~till.
Cor~pound No.20 of Table I 25
"PER~IINAL" BX* 1
"Dispersol" T 5~
Polyvinylpyrrolidone 10%
Silica 25~
C~ina clay 34%
* Re~. Trade Marks
7'3
F.,~MPL,E 21
The ingredients set out below were formulated into a
dispers~ble powcler by mixing then grinding the
i.ngredierlts .
Compound ~o. 2 of Table 1 25
"Aerosol" OT/B 2
"Dispersol" A* 5
China clay 68~
In Examples 1 to 10 the proportions of the
ingredients given are by weight and the Examples were all
repeated using, as active ingredient, the other compounds
of Table I.
There now follows an explanation of the composi.ions
or substances represented by the various Trade MarXs and
l'rade Names mentioned above.
15 L~BROL L : a condensate of nonyl phenol
(1 mole) with ethylene oxide
(1~ moles).
AROMASOL H : a solvent mi~ture of alkyl-
benzenes
20 DISPERSOL. T ~ND AC : a mixture of socium sul~hate
and a condensate of formalde-
hyde with sodium naphthalene
sul~honate
L~BROL APN 5 : a condensate o~ nonyl phenol
~5 (1 mole) with ethvlene oxide
(5.5 moles~
* Reg. Trade Mark
8~
CELLOFAS B600 : a sodium carboxymethyl
cellulose thickener.
EXAMPLE 22
The compounds were tested against a variety of foliar
fungal diseases of plants. The techniques employed were
as follows:
The plants were grown in John Innes Potting Compost (No.l
or 2) in 4 cm diameter mini-pots. A layer of fine sand
was placed at the bottom to facilitate uptake of test
compound by the roots. The test compounds were
formulated either by bead milling with aqueous
~ispersol T or as a solution in acetone or acetone/ethanol
which was diluted to the required concentration
immediately before use. For the foliage diseases
suspensions (100 ppm active ingredient) were sprayed on to
the foliage and applied to the roots of the same plant via
the soil. Exceptions ~ere the tests on Plasmopara viticola
_. .
and Venturia inaequalis in which the compound was sprayed
.
on to the foliage only. Sprays were applied to maximum
retention,and root drenches were applied to a final
concentration equivalent to approximately 40 ppm a.i./dry
soil. Tween 20, to give a final concentration of 0.05~ was
added when the sprays were applied to cereals.
E`or most of the tests the compound was applied to the
soil (roots) and to the foliage (by spraying) one or two
days before the plant was inoculated with the dlseases.
An exception was the test on Erysiphe graminis in which
the plants were inoculated 24 hours before treatment.
After inoculation, the plants were put into an
appropriate environment to allow infection to take place
and then incubated until the disease was ready for
- assessment.
81 ~ r~
The period between inoculation and assessment varied
fro~ four to fourteen days according to the disease and
environment.
The disease control was recorded by the -following
S grading:
4 = no disease
3 = trace - 5% of disease on untrea~ed plants
2 = 6-25~ of disease on untreated plants
1 = 26-59~ of disease on untreated plants
0 = 60-100% of disease on untreated plants
The results are shown in Table 6 below.
In the table below the following compounds have been
omitted for the reasons stated.
Compounds Nos. 5, 6, 7, 14, 16~ 21, 23, 25, 27, 29,
32, 40, 58, 88, 115, 123, 140 were not tested at the
standard primary screen rate.
Compounds Nos. 135, 136, 138, 142-145, 147, 148 and
160 were not tested.
A dash, thus "-", in the table in any column indicates
that the particular compound was not tested against that
particular disease.
An asterisk, thus "*" against the disease srading in
the column headed "BOTRYTIS CINEREA (TOMATO)" signifies
that the test plant material used in this instance were
grape l~erries. ~
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