Note: Descriptions are shown in the official language in which they were submitted.
39,3~5
4-PHENYLTHIOALKANESULFONANILIDES
AND DERIVATIVES THEREOF
This invention relates to alkanesulfonanilides sub-
stituted in the para position by a phenylthio, phenylsulfinyl
or phenylsulfonyl group, and additionally substituted by halo-
gen and/or trifluoromethyl, and to agriculturally acceptablesalts thereof. The compounds of the invention are active
herbicidal agents and plant growth modifying agents. The in-
vention also relates to herbicidal formulations containing
said compounds and to the use of the compounds to regulate
and control the growth of higher plants.
More particularly, the invention relates to com-
pounds of the formula
HNSO R
A ~ 2
B ~
5(0)~
o
wherein R is an alkyl group containing from l to 4 carbon
atoms or monohalomethyl~chloromethyl, bromomethyl, fluoro-
methyl or iodomethyl), A is halogen or CF3, B is hydrogen or
halogen and n is 0-2, provided that when A iS CF3 and B is
hydrogen, R cannot be methyl, and agriculturally acceptable
. : ~ : . : . ~ . :. .
3~8~
-- 2
salts thereof, to compositions for killing and modifying the
growth of higher plants consisting essentially of a compound
of the invention dispersed in an extending medium, to the use
of the compounds of the invention to modify the growth of
higher plants and to kill higher plants,and to processes for
~he preparation of the compounds of the invention.
The compounds of formula I, above, can form salts,
i.e~ compounds of ~he above formula wherein H is replaced by
an agriculturally acceptable cation~ These are generally
metal, ammonium and organic amine salts and can be prepared
by trea~ing the acid-form compound with an appropriate base
under mild conditions. Among the metal salts of the invention :
are alkali metal (e.g. barium, calcium and magnesium) and
heavy metal (eOg. zinc and iron) salts as well as other metal
salts such as aluminum. Appropriate bases for use in pre-
paring the metal salts include metal oxides, hydro~ides, car-
bonates, bicarbonates and alkoxides. Some salts are also
prepared by cation exchange reaction (by reacting a salt of
the invention with an organic or inorganic salt in a cation
exchange reaction). The organic amine salts include the
salts of aliphatic (e.g. alkyl), aromatic and heterocyclic
amines, as well as those having a mixture of these types of
structures. The amines useful in preparing the salts of the
invention can be primary, secondary or tertiary and prefer-
ably contain not more than 20 carbon atoms. Such amines in-
clude, for example,morpholine, methyl cyclohexylamine, glu~
cosamine, amines derived rom fatty acids~ etc. The amine
and ammonium salts can be prepared by reacting the acid form
. .
.
~ ~3~3~ ~
with the appropriate organic base or ammonium hydroxide.
Any of the salts of the types set out above are agricultural-
ly acceptable, the one chosen depending upon the particular
use and upon the economics of the situation. Of particular
utility are the alkali metal, alkaline earth, ammonium and
amine salts.
The salts of the invention are frequently formed
by reacting the precursors in aqueous solution. This solu-
tion can be evaporated to obtain the salt of the compound,
usually as a dry powder. In some cases, it may be more con-
venient to use a non-aqueous solvent such as alcohols, ace-
tone, etc. The resulting solution is then treated to remove
the solvent, for example, by evaporation under reduced pres-
sure.
lS The compounds of the invention can be prepared ac-
cording to the reaction sequences outlined in Methods l and
2 below.
Method l
NO2 NO2 NH2
B
Cl S - ~ ~3
NHSO2R NHSO2R N(SO2R)2
20 B ~ (5) ~ 1~(4) B
S()n~) S--~ S~3
.
- - -
3~3~ :
- 4 -
Step (1) of Method 1 is carried out by heating
equimolar amounts of a substituted 4-chloronitrobenzene and
benzenethiol in a suitable solvent in the presence of an
equimolar amount of base. The solvent is one in which the
reactants are soluble such as a lower alkanol (e.g. ethanol
or methanol), di~ethyl sulfoxide or dimethyl formamide. The
base is an organic or inorganic base. Suitable organic bases
are tertiary amines such as N,N-dimethylaniline, triethyl-
amine, pyridine, alkoxides such as sodium ethoxide and the
like. Suitable inorganic bases are alkali metal hydroxides
such as sodium and potassium hydroxide, calcium hydride and
th2 like. The product is isolated by conventional methods.
The reaction of step (2~ is a reduction of the ni-
tro group of the intermediate substituted 4-phenylthionitro-
benzene. Chemical or catalytic methods well known to theart are successful. Raney nickel is one suitable catalyst
for the reduction. Product is isolated by conventional meth-
ods.
The reaction of step (3) is the sulfonylation of
the intermediate substituted 4-phenylthioaniline with a sul-
~onyl chloride in the presence of base. If one to two equiv-
alents of sulfonyl chloride are used, a mixture of mono- and
bis-(sulonylated) product can be obtained which may be used
in step (4). More of the bis(sulfonylated) product can be
25 formed if two or more equivalents of sulfonyl chloride are ~;
reacted in the presence of a strong base.
Suitable bases for the reaction of step (3) are or
ganic and inorganic bases such as pyridine, triethylamine,
- , . .... ~., . :,
. . . . , - ~ ~. -:: - :
. . :
~ ~ ~3~3~
-- 5
dimethylcyclohexylamine, and substituted pyridines, and the
like. Liquid bases in excess can be used to eliminate the
need for a solvent. Stronger bases promote the formation of
bis(sulfonylated) product over mono(sulfonylation).
Step (4) is partial hydrolysis of the intermediate
bis(sulfonyl) compounds. This is a high yield reaction.
Basic hydrolysis using a strong base, such as potassium hy-
droxide in ethanol is u~ed. Alternatively, the precursor of
step (3) can be converted directly to the product of step ~4)
by means of a mono(sulfonylation~ reaction using one or more
equivalents of sulfonyl chloride and one or more equivalents
of base~ This reaction is favored by a base weaker than pyr-
idine, such as 3-bromopyridine.
Step (5) is carried out using conventional oxida-
tion methods such as hydrogen peroxide in acetic acid, sodium
metaperiodate and the like. The sulfoxide compound (n=l) is
produced when equimolar amounts of the oxidizing agent and
the reactant are utilized, whereas the sulfone (n=2) is pre-
pared directly utilizing 2 moles (or a slight excess) of the
20 oxidizing agent per mole of the reactant.
Method 2
(l) ~ (2) d
SCN S
:
The reaction of step (l~ of ~ethod 2 involves the
formation of the substituted 4-thiocyanoaniline from the cor-
..,
~3~3~5
- 6 -
responding aniline, generally by conventional means.
The reactions of step (2~ involves the formation of
the substituted 4-phenylthioaniline directly from the corres-
ponding 4-thiocyanoaniline. This reaction involves the for- 't',
mation of a sodium mercaptide from the thiocyano moiety by
reacting it with sodium sulfide in aqueous dimethylformamide
followed by its arylation (i.e. by heating the aqueous di-
methylformamide solution with cuprous oxide and an aryl ha-
like, preferably iodobenzene). This product is identical to
the precursor of step (3) of Method 1, and can be~converted
to the compounds of the invention in identical fashion.
The herbicidal activi~y of the compounds of the in-
vention has been determined using screening tests against
greenhouse plantings~ Both pre- and post-emergence activity
are determined in a direct screen against seIected weed
species. The f~llowing weeds are examples of weeds which are
used for these tests.
Grasses:
Giant foxtail (Setaria faberi)
~ Barnyardgrass (EehinochZoa crus-gaZIi)
Crabgrass fDigitarie ischaemum)
Quackgrass (Agropyron repens)
Yellow nutsedge (cyyeYus escuZentus)
Broadleaves:
~5 Pigweed (Amaran~hus retrofZexus)
Purslane (PortuZaca oZeracea)
Wild mustard (Brassica kaber)
Field bindweed (ConvoZvuZus arvensis)
:
.. . ~ , .- . - ,, , ~ : .:
_ 7 ~3~
The test chemicals are dissolved in a smal] amount
of acetone or other suitable solvent and -then diluted with
water to give a concentration of 2000 ppm. From this concen-
tration aliquots are diluted to give a final concentration of
500 ppmO Eighty ml. of this solution are added to a 6-inch
pot containing the weed seeds to give a concentration e~uiva-
lent to 20 lb/acre. Use of 20 ml. of said solution gives a
concentration equal to 5 lh/acre. All subsequent waterings
are made from the bottom. Two pots are used per treatment.
Data are taken 2 to 3 weeks after treatment and recorded as
percent pre-emergence kill for each species compared to the
untreated controls.
To assess post-emergence activity, the same weed
mixtures are allowed to grow from two to three weeks until
the grasses are approximately 1 to 3 inches and the broad-
leaves 1 to 1-1/2 inches tall. They are sprayed for approxi-
~mately 10 seconds or until good wetting of the leaf surfaces
occurs with a 2000 ppm. solution as described above
Data are taken two to three weeks after treatment
and recorded as percent kill for each species compared to the
untreated controls.
The compounds of this invention are broadly active
as herbicides. The mechanism(s) by which this herbicidal ac-
tivity is effected is not presently known. However, the com
pounds of this invention also show various types of plant
growth modifying activity. Plant growth modi ication as de-
fined herein consists of all deviations from natural develop-
ment, for example, defoliation, stimulation, stunting, re-
tardation, desiccation, tillering, dwarfing, regulation and
`.`
- , - - ::. . ~. , " .......... .
'`~1 : . :.! , :. ` :
~3~
,,
the like. This plant growth modifying activity is generally
observed as the compounds of the invention begin to interfere
with certain processes within the plant. If these processes
are essential, the plant will die if treated with a suffi-
S cient dose of the compound. However, the type of growthmodifying activity observed varies among types of plants.
For application to plants, the compounds can be
finely divided and suspended in any of the usual a~ueous
mediaO In addition, spreading agents, wetting agen-ts, stick-
ing agents or other ad~uvants can be added as desired. Drypowders, as such or diluted wlth inert materials such as dia-
tomaceous earth, can likewise be used as dusts for this pur-
pose. The preparations are coated on the plants or the ground
is covered when pre-emergence control is desired. Applica-
tion is made with the usual sprayers, dust guns and the like.Application rates are at 0.5 to 20 lbs/acre in general, but
may be increased or reduced according to individual circum-
stances of use.
The compounds of the invention may be advantageously
combined with other known herbicides to broaden or maximize
the weed spectrum controlled by herbicidal compositions of
this invention or to better control a weed not well controlled
by specific compounds of the invention. Among these other
known herbicides are phenoxy herbicides, e.g. 2,4-D, 2,4,5-T,
silvex and the like, carbamate herbicides, thiocarbamate and
dithiocarbamate herbicides, substituted urea herbicides, e.g.
diuron, monuron and the like, triazine herbicides, eOg. sima-
zine and atrazine, chloroacetamide and chlorinated aliphatic
acid herbicides, chlorinated benzoic and phenylacetic acid
~,3~5
g
herbicides, paraquat, nitralin and the like. Furthermore,
herbicidal compositions containing compounds of the inven~
tion may contain, in addition, nematicides, fungicides, in-
secticides, fertilizers, trace metals, soil conditioners,
other plant growth regulators and the like. Such combina-
tions are clearly envisioned in this invention.
The following examples are given for the purpose
of further illustrating the present invention but are not in-
tended, in any way, to be limiting on the scope thereof. All
parts are given by weight unless otherwise specifically noted.
Exam~le 1
2-Nitro~ henylthiobenzotr~fluoride.
A sQlution of 2-nitro 5-chlorobenzotrifluoride ~28.8
g., 0.15 mole), benzenethiol (16.6 g., 0.15 mole) and ethanol
(150 ml.) is heated to its reflux temperature under nitrogen.
To this solution is slowly added a solution of sodium hydrox-
ide (6 g., 0~15 mole) and water (7 ml.) at such a rate that
refluxing continues with no external heating. The solution
is then heated at its reflux temperature for an additional
~wo hours, filtered hot and the filtrate cooled. The re-
sulting precipitate is collected by filtration and recrys-
~tallized from hexane to afford a yellow solid, m.p. 65-67 C.
Analysis: ~C %H %N
Calculated for C13H~F3NO2S: 52~2; 2.7; 4.7
25 Found: 52.2; 296; 4.7.
The following compound can be prepared utilizing
the same general method:
2-chloro-4-phenylthionitrobenzene, a solid.
... .
3~31~;
Example 2
4-Phenylthio-2 trifluoromethylaniline.
2-Nitro 5-phenylthiobenæotrifluoride (25.6 g., 0.86
mole) in ethanol (500 ml.) is reduced over Raney nickel at
about 45 psi of hydrogen gas. After hydrogen uptake is com-
plete the mixture is deactivated with elemental sulfur, fil-
tered, and the filtrate evaporated under reduced pressure to
afford product as an oil. The infrared spectrum shows an ab-
sorption at 2.9~ (strong N~I band). The product crystallizes ~-
on standing to give a solid, m.p. 63-66.5 C.
The following compound can be prepared utilizing
the same general method:
2-chloro-4-phenylthioaniline, a solid.
Example 3
2-Bromo-4-phenylthloaniline.
A solution of 2-bromo-~-thiocyanoaniline (91.6 g.,
0.4 mole) and dimethylformamide is added dropwise to a solu-
tion of sodium sulfide (0~48 mole) and water, under nitrogen,
and the resulting solution is heated at 50 C. for one hour.
Cuprous oxide (34.33 g., 0.24 mole) and iodobenzene (97.9 g.,
0.48 mole) are added and the mixture is heated at a heating
bath temperature of 150 C. for 4.5 hours. The reaction is
quenched with water, methylene chloride is added and the re-
sulting mixture is filtered through filter aid to remove sus-
pended solids. The aqueous and organic layers are separated,and the aqueous layer is extracted three times with methylene
chloride. The methylene chloride extracts are combined,
washed with water and dried. Removal of the drying agent
,
:`" gL~3~L3135
-- 11 --
and methylene chloride gives the desired product, of which
a purified sample melts at 61-63 C.
Analysis: ~C ~H %N
Calculated for C12HlOBrNS: 51.44; 3.6; 5.0
5 Found: 51.9; 3.6; 5Ø
The following compounds cain be prepared utilizing
the same general procedure:
2-chloro-4 phenylthioaniline, a solid.
2-fluoro-4-phenylthioaniline, a solid.
2,3-dichloro-4-phenylthioaniline, a solid.
2,5-dichloro-4-phenylthioaniline, a solid.
Example 4
N-Chloromethylsulfonyl-4-phenylthio-2-trifluoromethylchloro-
methanesulfonanilide.
Chloromethanesulfonyl chloride (18.6 g., 0.125 mole)
is added dropwisa to a cold (0-5 C.), stirred solution of 4-
phenylthio-2-trifluoromethylaniline (13.5 g., 0.05 mole~ in
pyridine (20 g., 0.25 mole). The solution is stirred at room
temperature overnight, poured into ice water and 12 N hydro-
chloric acid with stirring to give N-chloromethylsulfonyl-4-
phenylthio-2-trifluoromethylchloromethanesulfonanilide as an
oil.
The following compound can be prepared utilizing
the same general method:
N-methylsulfonyl 2-chloro-4-phenylthiomethanesulfon-
anilide, a solid.
,,"~ ,"" , " ,",;"-~,,
- 12 - ~ ~3~3~
Example 5
, _ .
4-Phenylthio-2-trifluoromethylchloromethanesulfonanilide.
A solution of N-chloromethylsulfonyl-4-phenylthio-
2-trifluoromethylchloromethanesulfonanilide and 85 percent
potassium hydroxide (0.15 mole) in ethanol ~200 ml.) is
stirred overnight at room temperature. The solvent is re~
moved by filtration under reduced pressure, and the solid
product is taken up in hot Water~ filtered and then acidified
with dilute hydrochloric acid. The product is taken up in
methylene chloride and dried. Removal of the drying agent
and solvent gives an oil that crystallizes on standing. Re-
crystallization from methylene chloride-hexane gives a beige
solid, m~. 97-99 C
Analysis: ~C ~H ~N
Calculated for Cl~HllClF3NO2S2: 44.0; 2.9; 3-7
Found: 44.0; 2.9; 3.7.
- The following compound can be prepared utilizing
the same general method:
2~chloro-4-phenylthiomethanesulfonanilide, a solid.
Exam ~e 6
2-Bromo-4-thioc~anoaniline.
To a cold (0.5 C.), stirred solution of o-bromo-
aniline (20.6 g., 0.12 mole) and sodium thiocyanate (29.2 g.,
0.36 mole) in methanol (300 ml.) is added dropwise a solution
25 of bromine (19.5 g., 0.122 mole) in methanol (75 ml.) satu-
rated with sodium bromide. The solution is stirred -for one
hour following the addition of the bromine and then poured
into water (2 liters) and neutrali~ed with sodium carbonate.
.
,:
., . .: :.. - : .
,: , - ~
.
r - ~
; 13 -
The resulting solid is collected, washed with water and dried,
m.p. 74-79 C.
The following compounds are prepared using the same
general method:
2-chloro-4-thiocyanoaniline, m.p. 63-65 C~
2-fluoro-4-thiocyanoaniline, m.p. 34-35 C.
2,5-dichloro-4-thiocyanoaniline, m.p. 111-115 C,
2,3~dichloro-4-thiocyanoaniline, m.p. 132-137 C.
~ ~ -'.
10 2-Bromo-4-phenylthiomethanesulfonanilide.
Me~hanesulfonyl chloride t26.9 g., 0.23 mole) is
added dropwise to a cold (0-5 C.) solution of 2-bromo-4-
phenylthioaniline (52.5 g., 0.187 mole) in 3-chloropyridine
(163 g.), and the solution is warmed to room temperature and
stirred overnight. An additional ~uantity of methanesulfonyl
chloride (7 g.) is added, and the reaction mixture is heated
at 50 C. for 24 hours. The reaction mixture is mixed with
dilute hydrochloric acid and then extracted three times with
methylene chloride. The methylene chloride is washed three
times with water and dried. Removal of the drying agant and
methylene chloride leaves the desired product in crude form.
This product is leached with hexane, and the residue is
chromatographed on silica gel with methylene chloride eluant.
Removal of the methylene chloride eluant by evaporation gives
solid product that is recrystallized from hexane-methylene
chloride, m.p. 74.5-75 C.
Analysis: %C %H %N
Calculated for C13H12BrNO2S2: 43.58; 3.3~; 3-91
Found: 43.7; 3.4; 3O9
i
. ~ : :: . , .: -- .: ~ . .
- 14 ~3~$~
The following compounds are prepared using the same
general method:
2-chloro-4-phenylthiomethanesulfonanilide, m.p. 79.5-
~1 C.
2-fluoro-4~phenylthiomethanesulfonanilide, m.p. 125-
125~5 C.
The following compounds are also prepared using the
same general method except utilizing chloromethanesulfonyl
chloride or ethanesulfonyl chloride as appropriate:
2-bromo-4-phenylthiochloromethanesulfonanilide, m.p. 71-
72.5 C.
2-chloro-4-phenylthiochloromethanesulfonanilide, m.p. 73-
74 C.
2-fluoro-4-phenylthiochloromethanesulfonanilide, m.p.
~3-83.5Q C.
2,3-dichloro-4-phenylthiochloromethanesulfonanilide, m.p.
122-123.5 C.
2,5-dichloro-4-phenylthiochloromethanesulfonanilide, m.p.
144-144.~ C.
4-phenylthio-2-trifluoromethylethanesulfonanilide, a
solid.
Exam~le 8
4-Phen lsulfinyl-2-trifluoromethylchloromethanesulfonanilide.
.,.. , .Y .. . ~ . - - .. -' - - ;
To a stirred solution of 4-phenylthio-2-trifluoro-
2S methylchloromethanesulfonanilide (2.6 g., 0.0068 mole) in
glacial acetic acid (15 ml.) is added 30 percent hydrogen
peroxide tO.77 g., 0.0068 mole). The solution is stirred
overnight at room temperature, heated just to reflux then
~3'~3~
- 15
treated with water. The aqueous mixture if filtered, and the
tan solid is washed with water and dried, mOp. 146-150 C.
Analysis: ~C %H %N
Calculated for Cl~ 11 3 3 2
Found: 42.3; 3.0; 3.6.
The following compounds are prepared utilizing the
same general formula:
2-chloro-4-phenylsulfinylmethanesulfonanilide, m.p. 129-
129.5 C.
2-fluoro-4-phenylsulfinylmethanesulfonanilide, m.p. 121-
122.5 C.
2~bromo-4-phenylsulfinylmethanesulfonanilide, m.p. 138-
138.5 C.
2-fluoro-4-phenylsulfinylchloromethanesulfonanilide, m.p.
1~5-1~5.5 C.
2-bromo-4-phenylsulfinylchloromethanesulfonanilide, m.p. `~
123.5-124 C.
2-chloro-4-phenyIsulfinylchloromethanesulfonanilide, m.p.
142 143 C.
4-phenylsulfinyl-2-trifluoromethylethanesulfonanilide,
a solid.
Example 9
4-Phenylsulfonyl 2-trifluoromethylchloromethanesulfonanilide.
To a stirred solution of 4-phenylthio-2-trifluoro-
25 methylchloromethanesulfonanilide (2.6 g., 0.0068 mole) in
glacial acetic acid (lS ml.) is added 30 percent hydrogen
peroxide (3 g. r 0.0272 mole). The solution is heated at re-
flux for three hours, water is added, and the mixture is
~343~35
- 16 -
cooled. The resulting precipitate is collected by filtration,
washed with water and dried to gi~e a white solid, m.p. 93-
97 C.
Analysis: ~C %H ~iN
calculated for C14HllC1~3NgS2 40-6; 2-7; 3-4
Found: 40.6; 2.8; 3.5.
The following compounds are prepared utilizing the
same general method:
2-chloro-4-phenylsulfonylmethanesulfonanilide, a solid.
2-bromo-4-phenylsulfonylmethanesulfonanilide, m.p. 159-
160 C.
2-bromo~ phenylsulfonylchloromethanesulfonanilide, m.p.
136-136.5 C.
2-fluoro-4-phenylsulfonylmethanesulfonanilide, m.p.
127.5-128 C.
2-chloro-4-phenylsulfonylmethanesulfonanilide, m.p. 152-
156 C.
2-chloro-4-phenylsulfonylchloromethanesulfonanilide,
m.p. 142-142.5 C.
2-fluoro 4-phenylsulfonylchloromethanesulfonanilide,
m.p. 142-142.5 C.
4-phenylsulfonyl-2-trifluoromethylethanesulfonanilide,
a solid.
:: -.: : . :: . .
