Note: Descriptions are shown in the official language in which they were submitted.
~23~
-- 1 --
HERBICIDAL l-ARYL ~ ,4-TRIAZOLIN-5-ONES
The invention described in this application per-
tains to weed control in agriculture, horticulture, or
other fields where there is a desire to control unwanted
plant growth. More specifically, the present applica-
tion describes a series of novel herbicidal 1-aryl-
_1,2,4-triazolin-5-ones and 5-thiones, herbicidal
compositions of them, methods of preparing them, and
methods for preventing or destroying undesired plant
growth by preemergence or postemergence application of
the herbicidal compositions to the locus where control
is desired. The present compounds may be used to
effectively control a variety of both grassy and broad-
leaf plant species. The present invention is particu-
larly use~ul in agriculture, as a number of the novel
aryltriaæolinones descrihed herein show a selectivit~
favorable to soybean, corn, cotton, wheat, rice, sun-
flower, or other crops at application levels which
inhibit the growth of or destroy a variety of weeds.
Various herbicidal 1-aryl-~2-1,2,4-triazolin-5-
ones are known in the art. U.S. Patent No. 4,318t731
and corresponding British Patent No. 2,056,971 disclose
herbicidal aryltriazolinones of the formula
Cl ~ ~ R
X
wherein Rl is alkyl, R2 is hydrogen, alkyl, or alkenyl,
and X is hydroxy, alkyl, alkoxy, alkoxyalkoxy, alkenyl~
: ~k
6~
-- 2 --
oxy, or alkyloxycarbonylalkyloxy.
British Patent No. 2,090,250, a continuation-in-
part of the above British patent, adds to the above
genus compounds wherein R2 is alkynyl, halomethyl, or
haloethyl, and X is alkoxy, alkenyloxy, alkynyloxy,
alkoxyalkoxy, hydroxy, halomethyloxy, or haloethyloxy.
European Patent Application Publication No. 55,105
discloses a series of herbicidal aryltriazolinones of
the formula
10F O
XJ~ ~ Cl
wherein R is alkyl, alkenyl, or cycloalkyl, X is ch:lo-
rine or bromine, and Y is hydrogen or alkoxy.
Japanese Kokai 81-32,468 discloses herbicidal
aryltriazolinones of the formula
20~ N ~ N - R
Cl
E~
wherein R is hydrogen, alkyl~ or 2-propenyl, and R1 is
methyl or alkoxy.
South African Patent Application No. 78/3182
discloses herbicidal aryltriazolinones of the formula
30O
R~ ~ ~ ~ Rl
wherein Rn is hydrogen or represents 1 to 4 same or
different radicals selected from halogen, nitro, cyano,
.,
~2~6~
-- 3 --
optionally halosubstituted alkyl, alkoxy, or alkylthio,
and optionally substituted phenyl or phenoxy, and R
is alkyl, alkoxyalkyl, dialkoxyethyl, dialkylaminoethyl,
or cycloalkyl.
U.S. Patent No. 4,315,767 discloses herbicidal
bicyclic compounds of the following formula
Y Q
~ ~(CH2 ) n~z
X~ (CH2)m~
V
wherein V is hydrogen, halogen, methyl, or alkoxy, X is
hydro~en, halogen, cyano, methyl, methoxy, or nitro, Y
is hydrogen, halogen, or methyl, m and n are O to 4 ~m
plus n is 2 to 4), ~ is oxygen or sulfur, and Z is
oxygen, S(O)p, or NR1 wherein p is 0-2 and R1 is alkyl,
provided that when m plus n is 2 or 4 then Y and X are
other than hydrogen, and when Z is S(O)p then n is 1
to 4.
Additional herbicidal bicyclic compounds based on
aryltriazolinones are disclosed in U.S. Patent No.
4,213,773 and have the following structural formula
Q
~ CH2)n
V (CH3)m
wherein V is hydrogen, halogen, hydroxy, alkyl, or -OR ;
R1 is optionally substituted alkyl, cycloalkyl, cyclo-
alkylalkyl, optionally substituted alkenyl, alkynyl,
optionally substituted benzyl, alkylaminocarbonyl,
~alkyl) ~methyl or methoxy)aminocarbonyl, acyl; alkoxy-
carbonyl, or -CHR7R8 wherein R is hydrogen or alkyl
and R8 is cyano, acetyl, hydroxycarbonyl, alkoxycar~
bonyl, hydroxymethyl, alkoxymethyl, alkylcarbonyloxy-
methyl, hydroxycarbonylethenyl, alkoxycarbonylethenyl,
or a group -CO-~R11R12 wherein Rll is hydrogen, alkyl,
alkenyl, or alkoxy, and R12 is hydrogen or alkyl; X is
halogen, cyano, methyl, methoxy,. or nitro; Y is hydro-
gen, halogen, or methyl; Z is hydrogen or halogen; n is
3-5; m is 0-2; and Q is oxygen or sulfur, with certain
10 provisos-
A class of ~ -1,2,4-triazolin-5-ones is disclosed
as fungicides in U.S. 4,098,896. The disclosed genus
has the for~ula
Rl s--T N
N ~ sR2
wherein R is alkyl, alkenyL, alkynyl, cycloalkyl, or
optionally substituted phenyl or arylalkyl, R1 is
haloalkyl or haloalkenyl, and R2 is optionally substi-
tuted alkyl~ alkenyl, or alkynyl, or optionally substi
tuted aryl, arylalkyl, or alkylaryl.
The present application describes a novel class of
herbicidal 1-ary.l-~ -1,2,4-triazolin-5-ones and 5-
thiones characterized primarily in that the l-aryl
moiety is a 2,4,5-trisubstituted-phenyl group in which
the C-5 substituent is a group -OR wherein R is an
oxygen-, sulfur- or nitrogen-containing heterocycle or
an alkyl group substituted therewith.
L~3
-- 5 --
Any alkyl, alkenyl, or alkynyl group herein or the
alkyl, alkenyl, or alkynyl portion of any group may
be a straight chain or branched chain radical. Thus,
1-methylethyl, methylcyclopropyl, 2-methyl-2-propenyl,
and 1-methyl-2-propynyl are branched chain examples of
alkyl, cyclic alkyl, alkenyl, and alkynyl radicals
respectively. Any halogen may be fluorine, chlorine, or
bromine. Haloalkyl, haloalkenyl, and haloalkynyl
radicals may have one or more same or different halogen
atoms. Any aryl group or the aryl portion of any group
may be a hydrocarbyl group such as phenyl or it may
contain one or more heteroatoms such as in thienyl or
furyl. Any aryl may be substituted, for example, with
halogen or alkyl of 1 to 4 carbon atoms.
The compounds of this invention have the formula
xl q~
x2 ~ R2
R
in which X1 and x2 are independently selected from
halogen, haloalkyl, and alkyl;
W is oxygen or sulfur;
R is a three- to eight-membered ring heterocyclic
group of one or two, same or different, ring heteroatoms
selected from oXygenr sulfur, and nitrogen, or an alkyl
radical substituted with said heterocyclic group;
R1 is alkyl, haloalkyl, ~yanoalkyl, alkenyl,
alkynyl, or a group of the formula -alkyl-Y-R ;
3.~3~ 3~
-- 6
R2 is halogen, alkyl, cyanoalkyl, haloalkyl,
arylalkyl, or a group of the formula -alkyl-Y-R ;
~3 is alkyl, alkenyl, or alkynyl; and Y is oxygen
or S(O) in which r is 0 to 2.
5The R substituent heterocyclic group may be sat-
urated, unsaturated, or aromatic. It may be subs~ituted
with halogen, alkyl, or haloalkyl, or it may be adjoined
to a benzene ring at two adjacent ring carbon atoms to
form a benzoheterocycle bicyclic group, the two adjacent
ring carbon atoms being common to both the heterocyclic
ring and the benzene ring. In sulfur-containing hetero-
cycles, the sulfur may be present in divalent form or as
the S-oxide or S-dioxide.
One aspect of the present invention comprises the
compounds of formula I above wherein R is an optionally
substituted and optionally benzene adjoined nitrogen-con-
tainin~ heterocycle or an alkyl radical of l to S carbon
atoms substituted with said heterocycle. Preferably, the
R substituent for this group of compounds is a non-aro-
matic heterocycle, preferably containing only one nitro-
gen atom and no other heteroatoms, the nitrogen atom
preferably being substituted with an alkyl group of 1 to
5 carbon atoms, particularly a methyl group. This aspect
of the invention is exemplified herein by compounds 29
and 31 below wherein R is l-methyl-3-pyrrolidinyl.
A second aspect of the present invention comprises
the compounds of formula I above wherein R is an aro-
matic, optionally substituted and optionally benzene-
adjoined, oxygen- or sulfur-containing heterocycle or an
alkyl group of 1 to 5 carbon atoms substituted therewith.
Preferably, R is an optionally substituted furanyl,
furanylalkyl, thienyl, or thienylalkyl radical. In the
exemplary compounds 10 and 11 below, K is furfuryl and
2-thienylmethyl respective~y.
35A further aspect of the present invention comprises
the cornpounds of formula I above wherein R is a non-aro-
~23~
-- 7
matic, optionally substituted and optionally benzene~
adjoined, oxygen- or sulfur-containing heterocycle or an
alkyl group of 1 to 5 carbon atoms substituted therewith.
This group of compounds represents a preferred embodiment
of the present invention. The R substitLlent heterocycle
is preferably saturated, but may be unsaturated, and is
preferably unsubstituted or substituted with alkyl
of 1 to 5 carbon atoms, particularly methyl, or it may
be substituted with halogen such as fluorine, chlorine,
or bromine or haloalkyl of 1 to 5 carbon atoms, for
example, chlorodifluoromethyl. Where the R heterocycle
contains two ring heteroatoms, they may be the same or
different, oxygen or sulfur, preferably the same, and
are separated from each other in the ring by at least
one carbon atom. In sulfur-containing heterocycles,
the sulfur may be present in divalent form or as the
S-oxide or S-dioxide. The R substituent heterocycle for
these compounds of the invention will be recognized as
being a cyclic ether or thioether or an S-oxide or
S-dioxide derivative of a cyclic thioether. Examples
of ~ groups for this subgenus are 3-tetrahydrofuranyl,
tetrahydrofurfuryl, tetrahydropyran-2-ylmethyl, 1,3-di-
oxolan-2-ylmethyl, 2-(1,3-dioxolan-2-yl)ethyl, 2,2-di-
methyl-1,3-dioxolan-4-ylmethyl, 3-(2-methyl-1,3-dioxo-
lan-2-yl)propyl, 1,3-dioxan-4-ylmethyl, 1,4-benzodioxan-
2-ylmethyl, tetrahydro-4H-pyran-4-yl, 5,6-dihydro-2H-
pyran-3-ylmethyl, 2,2-dimethyl-1,3-dithiolan-4-yl-
methyl, tetrahydro-4H-thiopyran-4-yl, tetrahydrothien-
3~yl, 1-oxotetrahydrothien-3-yl, 1,1-dioxotetrahydro-
thien-3-yl, 2,2-dimethyl-1,1,3,3-tetraoxo-1,3-dithiolan-
4-ylmethyl, and 1,1-dioxotetrahydro-4H-thiopyran-4-yl.
Additional examples include 1,4-dithiacycloheptan-6-yl,
1,4-dithiacyclohept-5-ene-6-yl, tetrahydro-4H-pyran-3-
yl, glycidyl, 2,3-epithiopropyl, and 2,2-bis(chlorodi-
fluoromethyl)-1,3-dioxolan-4-ylmethyl.
Of especial interest is the genus comprising the
~236~3
compounds of formula I above in which X and X are
independently selected from halogen, haloalkyl of 1 to 3
carbon atoms, and alkyl of 1 to 5 carbon atoms;
W is sulfur or, preferably~ oxygen;
5R is 1~methyl-3-pyrrolidinyl, furfuryl or 2-thien-
ylmethyl, or preferably 3-tetrahydrofuranyl, tetrahydro-
furfuryl, tetrahydropyran-2-ylmethyl, 1,3-dioxolan-2-yl-
ethyl, 2-(1,3 dioxolan-2-yl)ethyl, 2,2-dimethyl-1,3-di-
oxolan-4-ylmethyl, 3-(2-methyl-1,3-dioxolan-2-yl)propyl,
1,3-dioxan-4-ylmethyl, 1,4-benzodioxan-2-ylmethyl,
tetrahy~ro-4H-pyran-4-yl, 5j6-dihyd~o-2~-pyran-3-yl-
methyl, 2,2-dimethyl-1,3-dithiolan-4-ylmethyl, tetrahy-
dro-~H-thiopyran-4-yl, tetrahydrothien-3-yl, 1-oxotetra-
hydrothien-3-~l, 1,1-dioxotetrahydrothien-3-yl, 2,2-di-
15 meth~l-1,1,3,3-tetraoxo-1,3-dithiolan-~-ylmethyl, 1,~-
dithiacycloheptan-6-yl, 1,4-dithiacyclohept-5-ene-6-yl,
tetrahydro-4H-pyran-3-yl, glycidyl, 2,3-epithiopropyl,
2,2-bis(chlorodifluoromethyl)-1,3-dioxolan-4-ylmethyl,
or 1,1-dioxotetrahydro-4H-thiopyran-4-yl;
20R is alkyl, haloalkyl, or cyanoalkyl of 1 to 5
alkyl carbon atoms, alkenyl or alkynyl of 2 to 5 carbon
atoms, or a group (CH2)n-Y-R wherein n is 1 to 5;
R2 is halogen, alkyl, haloalkyl, cyanoalkyl, or
arylalkyl wherein each alkyl is of 1 to 5 carbon atoms,
25 or a group (CH2)n-Y-R wherei~ n is 1 to 5;
R is alkyl of 1 to 5 carbon atoms or alkenyl or
alkynyl of 2 to 5 carbon atoms; and
Y is oxygen or S()r in which r is 0 to 2.
The substituents X and X may be the same,
and in such instances each will usually be a fluorine,
chlorine, or bromine atom (preferably chlorine); less
fre~uently, a methyl group. ~hen X1 and x2 are dif-
ferent, X will advantageously be fluorine or chlorine,
preferably fluorine, and x2 will frequently be select-
ed from among chlorine, bromine, haloalk~l such as
~23~ 3
g
difluoromethyl~ and alkyl such as methyl. x2 is pre-
ferably chlorine.
The R1 substituent is preferably a haloalkyl radi-
cal of 1 to 3 carbon atoms and having one or more in-
dependently selected halogen atoms, preferably selectedfrom fluorine and chlorinej more preferably, a fluoro-
alkyl radical such as 3-fluoropropyl or, especially,
difluoromethyl. Other R substituents of particular
interest include alkyl of 1 to 5 (preferably 1 to 3)
carbon atoms such as n-propyl, cyanoalkyl of 1 to 3
alkyl carbon atoms such as cyanomethyl, alkenyl of 2 to
(preferably 3 to 5) carbon atoms especially 2-pro-
penyl, alkynyl of 2 to 5 (preferably 3 to 5) carbon
atoms such as 2-propynyl, or a group -(CH2)2-Y-R in
which Y ~s oxygen or sulfur and R3 is alkyl of l to
(especially 1 or 2) c~rbon atoms such as Inethyl
Frequently R1 will be selected from n-propyl difluoro-
~ethyl, 3-fluoropropyl, cyanomethyl, and 2-propenyl.
R2 is preferably alkyl of 1 to 5 (more preferably
1 to 3) carbon atoms, especially methyl; haloalkyl of 1
to 3 carbon atoms, particularly a fluoroalkyl such as
fluoromethyl or difluoromethyl; cyanoalkyl of I to 3
alkyl carbon atoms, for example, cyanorlethyl; benzyl; or
a group -(CH2)n-Y-R in which n is 1 or 2, Y is oxygen
or sulfur, and R is alkyl o~ 1 to 5 carbon atoms such
as methyl or ethyl. R2 will frequently and advanta-
geously be fluoromethyl, difluoror~lethyl, or, especially,
unsubstituted methyl.
Compounds in which the R substituent is 3-tetrahy-
drofuranyl, tetrahydrofurfuryl, or 1,1-dioxotetrahydro-
thien-3-yl, particularly 3-tetrahydrofuranyl, generally
show very high herbicidal activity, especially where
preferred groups are selected for the other substitu-
ents. Other preferred radicals ~or R include: tetra-
hydropyran-~-ylmethyl, 1,3-dioxolan-2-ylmethyl, 2-(1,3-
dioxolan-2-yl)ethyl, 2,2-dimethyl-1,3-dioxolan-4-yl-
~ .
- 10 -
methyl, 1,3-dioxan-4-ylmethyl~ tetrahydro-4H-pyran-4-yl,
tetrahydrothien-3-yl, and 1-oxotetrahydrothien-3-yl.
Also of particular interest are compounds wherein R is
3-(2-methyl-1,3-dioxolan-2-yl)propyl, 5,6-dihydro-2H-
pyran-3-ylmethyl, 2,2-dimethyl-1,3-dithiolan-4-ylmethyl,
or tetrahydro-4H-thiopyran-4-yl.
The present compounds may generally be prepared by
reaction of an appropriately substituted 5-hydroxyphenyl-
triazolinone (01a) or the thione analog (Olb) with R-X,
wherein X is a good leaving groupl in the presence of a
base as illustrated in the following equation.
l5 ~ ~ ~ - Rl~ R X base~> ~ ~ ~ R
N I I _~ I
OH R2 x2 ~ N ~R2
OR
l Ia
Satisfactory results have been obtained with sodium
hydride base in dimethylforma~lide for reactions in which
the leaving group X is 4-methylphenylsulfonyloxy, bromine,
or chlorine~
The present compounds containing a sulfinyl or a
sulfonyl yroup in R, R1, or R2 may be prepared by
oxidation of the corresponding thio compound, generally
with hydrogen peroxide, as described in detail in Ex-
amples 25, 26, 27, and 34 below for certain R groups.
The aryltriazolin-5-thiones (W is sulfur) may
be prepared by methods within the skill of the art; for
example, by treating an appropriately substituted
aryltriazolin-5-one with phosphorous pentasul~ide in
~3Ç~3
toluene under reflux conditions. The C=O to C=S conver-
sion step may be conducted prior to subsequent to the
addition of the R substituent to the heterocyclic
ring.
The intermediates R-X and 01a are ei-the:r known in
the art and, therefore, are available by known methods,
or may be prepared by methods analogous or similar to
known methods or by methods within the skill of the art.
For example, U.S. Patent No. 4,318,731 and British
Patent No. 2,090,250 disclose preparation of a number of
the present hydroxyphenyl intermediates 01a wherein X
and x2 are chlorine atoms by dealkylation of the
corresponding allcyloxyphenyl or alkenyloxyphenyl com~
pound. Many oE the hydroxyphenyl intermediates 01a
Eor -the present exemplary compounds were prepared by
dealkylation of the corresponding isopropoxy or methoxy
compound in the presence of concentrated sulfuric acid,
a mixture of hydrobromic and acetic acids, or boron
tribromide.
Further methods for preparing intermediate com-
pounds are illustrated in the following chemical equa-
tions in which steps A and B are analogous to the method
of U.S. Patent 3,290,327, issued December 6, 1966.
(A) R2COCl -~ H2NCO2C2H5 ~ R CoNHco2c2~l5
;~) 02 + X ~
OCH3 OCH3
03 04
' !
'`/' .' .
-- 12 --
xl S
(C) 04 p2S5 X2~_~J N H
- toluene ~ N~ 2
3 05 R
Rl-X/base 2 / < _N R
(D) 05 (x=leaVing group) ~ X ~ N~ 2
OCH3 06 R
(E) 06 CH2 2 ~ ~2
1_
Phenylhydrazines (03~ use:Eul in step B above
may be prepared by the method shown in the following
chemical equations in which step F itself represents
a 5-step conversion and is analogous to the metod o~
E. Nagano et al., European Patent Application 6~,855.
xl xl
(F) x2 ~ > X ~ ~ NH2
OH OCH3
07 ~ 08
, . .
.
~., : '`
~23~631
- 13 -
(l) NaNO~/HCl ~
(G) (2) SnCl2-H2O/HC~ ~ ~ NHNH2
-5 to OC OC~3
_03
Alternatively, where X and X are halogen such as
chlorine, such substituents may be added to the ~olecule
later in the reaction sequence, 3-methoxyphenylhydrazine
being used in step B. For example compound 06 in which
X1=X2=H may be treated with sulfuryl chloride to g:ive
the corresponding compound in which X =X =Cl.
15 An alternative method for producing the aryltria
zolinone 04 from the phenylhydrazine 03 is shown in the
following chemical equations.
/ ' R2
2 C2H5OH ~NHN ~CO H
OCH 3
09
(I) 09 + ( 6H5)2P()N3 Tolu5 3 ~ 04
reflux
The preparation, properties, and herbicidal acti-
vity of representative herbicidal compounds of this
invention are illustrated further.in the examples below.
35 All temperatures shown are in degrees Celsius, and all
pressures are in mm Hg.
,.::'.
~316~
Representative compounds of the invention are
identified by chemical structure in the following table
wherein the compound numbers correspond to Example
numbers.
Table 1
Represent~ Com~ounds
xl
t~N~N~R
x2 ~ ~ R2
Cpd~ ~ aR 2
No X X R R R W
_ _ __
1Cl Cl~ J CF2H CH3 0
2 Cl ClCH ~ ~ CF2H CH3 0
3 Cl ClCH2 ~ ~ CH2CH-CH2 CH3 0
4 Cl ClCH ~ CF2H 3
S Cl ClCH ~ CH2CH= Q 2CH3 0
6 Cl ClCH ~ ~ CF2H CH3 0
7 Cl Cl CH2CH ~ ~ CF2H C~3 0
8 Cl C1CH2-lr--~ CF2H CH3 0
CH3~H3
(CH2) ~ CF2H CH3 0
10 Cl ClCH ~ .J ~ CF2H CH3 0
11 Cl ClCH2- ~ CF2H CH3 0
12 Cl ClCH2 - ~ ~ CF2H CH3 0
13 Cl ClCH ~ o ~ CF2H CH3 0
14 Cl Cl~ CF2~ CH3 0
15 Cl C1CH2 ~ CF2H CH3 0
16 Cl ClCH2.roJ CH2CH=CH2CH3 0
17 Cl Cl~ CH2CH=CH2CH3 0
~2~ 3
- 15 -
No. X X R Rl - R2_ W
18 Cl Cl ~ n~C3H7 C~3 0
19 Cl Cl CH ~ n~C3H7 CH3 0
Cl ClCH2 ~ S ~ CH3 CF2l~ CH3 0
21 Cl Cl ~ CF2H CH3 0
22 Rr Br ~ CF2H C~3 0
23 Br Br CH2 ~ CF2H CH3 0
24 Cl Cl ~ CF'2H CH3
Cl Cl ~ SO CF2H CH3 0
26 Cl Cl ~ ~2 C~2H CH3 0
SO~
27 Cl ClCH2 ~ ~ CH3 CF2H CH3 0
23 Cl CH3 ~ CF2H CH3 0
29 Br Br ~ CF2H C~13 0
Br CH3 ~ ~13 CF2H CH3 0
31 Cl Cl ~ CF2H CH3 0
32 Cl CH3 ~ CF2H CH3 0
33 Cl OEl ~ CF2H CH3 0
3CH ~ OJ
34 Cl Cl ~ 2 CF2H CH3 0
Cl Cl ~ CH2CH=CH2 Cl 0
36 Cl Cl 'J CF2H C2H5 0
37 Cl Cl ~J CF2H C(CH3)3 0
38 F Cl ~ J CF2H C~13 0
39 F Cl CH ~ CF2H CH3 0
F Cl ~SJ CF2H CH3 0
- 16 -
Cpdo 1 2 R R ~_~____ R2 W
41 F Cl ~ CF2H CH3 0
42 F ClCH2 ~ ~ CF2H C~3 0
43 Cl F ~ CF2~ CH3 0
44 F F ~ CF2H CH3 0
F Cl { ~ CF2H Ch3
46 F Cl CH2 ~ CF2H C~3 0
47 F Cl CH2 ~ CF2H CH3 0
CH2 r~H CF2H CH3 0
49 F Cl - ~ CF2H CH3 0
F Cl ~ ~ CF2H C~33 0
51 F Cl ~ CFH2 C~]3 0
52 E' Cl ~ (CH2)3F C~33 0
53 F ~oJ CH C-CH CH3 0
54 F Cl ~ (CH2)2OCH3 CH3 0
F Cl ~J CF2H 2 6 5
56 F Cl 'J CF2H CH2OCH3 0
57 F Cl ~ CF2H CH2SCH3 0
58 F Cl ~ ' CF2H C2H5 0
59 F CH3 ~ CF2H CH3 0
F CFH2 ~ CF2H CH3 0
61 Cl CFH2 ~ CF2H C~3 0
62 F Cl ~ CF2H CH2CN 0
63 F Cl CH2 - rO ~ F2Cl CF28 CH3 0
CF2Cl
. .
~23~
- 17 -
No ~ X 1 X2 R - Rl R2~ W
64 F Cl ~J CF2H CF;;~H 0
F Cl ~ CF2H ., CH2(N
66 F Cl ~ CF2CHClF CH3 0
67 F Cl ~J CH2C~ CH3 0
68 F Cl ~ CH3 (~i3 0
69 F Cl ~ ( 2 ) 2 3 CH3 0
F Cl ~ CF2H CH3 S
71 F ClCHz~--~ CF2H Cf~3 S
72 Cl Cl ~ CF2H C~13 S
73 F Cl ~ (C~12)2S(O)CH3 C1~13 0
74 F Cl ~ (CH2)2S(O)CH3 CH3 S
F Cl ~ (CH2)2S~0)2CH3 C~13 0
76 F Cl ~J CF2H CH2S(O)CH3 0
77 F Cl ~J CF2H CH2S (O) 2CH3 0
78 F Cl ~o) (CH2)20CH2CH=CH2 CH3
79 F Cl ~J (CH2)20 H2C~CH CH3
Cl Cl CH2~ CH2CN CE13 0
81 F Cl ~J ~ CH2CN CF2H 0
82 F Cl ~ J CFH2 C 2H 0
83 Cl Cl ~ CF~2 C~3
84 F CFH2 ~] CH2CN CH3 0
Cl Cl ~ (CH2)3F CH3 0
86 F F ~ (CH2)3F CH3 0
87 F Cl ~ ~F2H CFH2 0
~3~3
- 18 -
Example 1
1-[2,4-DICHLORO-5-(3-TETRAHYDROFURA~YLOXY)P~ENYL]-
3-METHYL-4-DIFLUOROMETHYL-~ 1,2,4 1'RIAZOLIN-5-ONE
Step 1: 3-Tetrahydrofuranyl 4-methylphenylsulfonate
A stirred solution of 10.0 g (O. 11 mole~ of 3-hy-
droxytetrahydrofuran in 36.0 g (0.46 mole) of pyridine
was cooled in an ice bath and 22.0 g (0.12 mole) of
4-methylphenylsulfonyl chloride was added. Upon com
plete addition, the reaction mixture was stirred at
ambient temperature for 60 hours. The reaction mixture
was poured into ice-water, and the mixture extracted
with diethyl ether. The combined ether extracts were
washed several times with water. The organic layer was
dried with magnesium sulfate, filtered, and the filtrate
concentrated under reduced pressure to give 2t.4 g of
lS 3-tetrahydrofuranyl ~-methylphenylsulfonate.
The nmr spectrum was consistent with the proposed
structure.
Step 2: 1-[2,4-Dichloro-5~(3-tetrahydrofuranyloxy)-
phenyl]-3-methyl-4-difluoromethyl- Q2_1,2,4-triazolin-5-
one
To a stirred mixture of 1.0 g ~0.003 mole) of
1-(2,4-dichloro-5-hydroxyphenyl)-3-methyl-4-difluoro-
methyl- Q2_1,2,4-triazolin-5~one and 0.08 g (0.003 mole~
of sodium hydride (0.16 g o~ 50% dispersion in mineral
25 oil) in dimethylformamide was added 008 g (0.003 mole)
of 3-tetrahydrofuranyl 4-methylphenylsulfonate. Upon
complete addition, the reaction mixture was heated to
reflux and stirred for 16 hours. The reaction mixture
was concentrated under reduced pressure to give a residue
which was dissolved in diethyl ether and washed with
aqueous tO% sodium hydroxide. The organic layer was
dried wi~h magnesium sulfate, filtered, and the filtrate
concentrated under reduced pressure to give a residual
oil. The oil was stirred with petroleum ether until a
solid formed. The solid was collected by filtration to
- ~23~3
_ 19 _
give 0.78 g of 1-[2,4-dichloro-5-(3-tetrahydrofuranyl-
oxy)phenyl]-3-methyl-4-difluoromethyl- ~2 1~2~4~tri-
azolin-5-one; mp 113-116C.
The nmr spectrum was consistent with the proposed
structure.
Example 2
1-(2~4-nIcHLoRo-5-TETRAHyDRoFuRFuRyLoxypHE~yL)-3
METHYL-4-DIFLUOROMETHYL-~2-1 t 2,4-TRIAZOLIN-5-ONE
A stirred mixture of 0.75 g (0.0024 mole) of 1-(2,4-
dichloro-5-hydroxyphenyl)-3-methyl-4-difluoromethyl-
~ -1,2,4-triazolin-5-one and 0.059 9 (0.0024 mole) of
sodium hydride ~0.12 g of 50~ dispersion in mineral oil)
in 8 mL of dimethylformamide was warmed to 105C. The
mixture was cooled to 70C, and 0.40 g (0.0024 mole) of
tetrahydrofurfuryl bromide was added. Upon complete
addition, the reaction mixture was heated at 75-80C for
30 minutes, then allowed to cool to ambient temperakure
and was stirred for 16 hours. The reaction mixture
was warmed to 125-145C and stirred for 3.5 hours. An
additional 3-4 drops of tetrahydrofurfuryl bromide was
added, and the reaction mixture was stirred at 125-145C
for an additional 1.5 hours. The mixture was cooled and
concentrated under reduced pressure to give a residual
oil which was partitioned between diethyl ether and
water. The ether layer was washed with water, aqueous
10~ hydrochloric acid, water, aqueous 10~ sodiu~ hydrox-
ide, and finally two portions of water. The organic
layer was dried over magnesium sulfate, filtered, and
the filtrate concentrated under reduced pressure to give
a residual oil. The oil was stirred with cold petroleum
ether until a solid formed. The solid was collected by
filtration to give 0.25 g of 1-(2,4-dichloro-5-tetrahy-
drofurfuryloxyphenyl)-3-methyl-4-difluoromethyl- ~2_
1,2,4-triazolin-5-one. A sample was recrystallized from
ethanol/water for analytical purposes; mp 95-9705Co
~3~ 3
- 20 -
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C15H15C12F2N3O3: C 45.70; H 3. 84:
~ 10.65;
Found: C 45.68; H 4.05;
N 10.35
Exam~le 3
1-(2,4-DICHLORO-5-TETRAHYDROFU~FURYLOXYPHENYL)-3-
METHYL-4-(2-PROPENYL)-~ -1,2,4-TRIAZOLIN-5-ONE
. _
In the manner of Example 1, treatment of 0.75 g
(0.0025 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-3-
methyl-4-(2-propenyl)- Q -1,2,4-triazolin-5-one with
0.41 g (0.0025 mole) of tetrahyd~rofurfuryl bromide in the
presence of 0.06 g (0.0025 mole) of sodium hydride and
dimethylformamide at room temperature for 16 hours, then
15 at reflux for 2 hours gave 0.45 g of product as an
oil.
The nmr spectrum was consistent with the proposed
structure.
Example 4
1-[2,4-~ICHLORO-S-(TETRAHYDROPYRAN-2-YLMETHOXY)-
PHENYL]-3-METHYL-4-DIFLUOROMETHYL- ~ -1,2,4-TRI-
AZOLIN-5-ONE
.
A mixture of 1.0 g ~0.0032 mole) of 1-(2,4-dichloro-
5-hydroxyphenyl)-3-methyl-4-difluoromethyl-~ -1,2,4-
triazolin-5-one and 0.078 g t0.0033 mole) of sodium
hydride in 12 mL of dimethylformamide was heated to
reflux, then cooled to room temperature. Tetrahydropy-
ran-2-ylmethyl bromide (0.58 g, 0.0032 mole) was added
dropwise over one minute, and the reaction mixture was
heated with stirring at reflux temperature for 2 hours.
The mixture was allowed to cool to room temperature and
was stirred for about 64 hours, then heated again at
reflux temperature for 2 hours. An additional 0.2 g
(0.0011 mole) of tetrahydropyran-2-ylmethyl bron~ide was
- 21 -
added and refluxina was resumed for an additional 2
hours.
The reaction mixture was cooled and concentrated to
dryness to give an oily black residue which was parti-
tioned between diethyl ether and water. The ether layerwas washed sequentially with 10% hydrochloric acid,
water, 10~ aqueous solution of sodium hydroxide, water~
and brine. The ether layer was dried over magnesium
sulfate, filtered, and the filtrate concentrated to give
0.82 g of a viscous yellow oil. The oil crystallized
upon treatment with petroleum ether to give 0.46 g
of product, mp 101-102C.
The nmr spectrum was consistent with the proposed
structure.
15 Analysis calcd for C16H17Cl2F2N3O3: C 47.08; H 4.20;
N 10.30;
Found: C 46.79; H 4.137
N 10.39.
Example 5
1-[2,4-DICHLORO-5-(TETRAHYDROPYRAN-2-YLMETMOXY)-
Pl1ENYL]-3-METHYL-4-(2-PROPENYL)- ~ -1,2,4-TRI-
AZOLIN-5-ONE _ _
In the manner of Example 4, 0.89 g (0.005 mole) of
tetrahydropyran-2-ylmethyl bromide was added at room
temperature to a previously h~eated then cooled mixture of
1.5 g (0.005 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-3-
methyl-4-(2-propenyl)- ~ -1,2,4-triazolin-5-one and 0.13
g (0.0055 mole) of sodium hydride in 10 mL of dimethyl-
formamide. The mixture was stirred at reflux temperature
for 1.5 hours, then at room temperature for 16 hours, and
finally at reflux temperature for an additional 2
hours. The mixture was diluted with water, extracted
with diethyl ether, and the ether layer treated as in
Example 4 to give 0.81 9 of product as an oil.
The nmr spectrum was consistent with the proposed
~%3~
- 22 -
structureO
Example_6
1-[2,4-DICHLORO-5-(1,3-DIOXOLAN-2-Yl.METHOXY)PHENYL]-
3-METHYL-4-DIFLUOROMETHYL- ~ -1,2,4-TRIAZOLIN-
5-ONE _ _
In the manner of Example 4, 0.44 9 (0.0026 mole) of
1,3-dioxolan-2-ylmethyl bromide was added to a previously
heated (110C) then cooled (25C) mixture of 0.75 g
(0.0024 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-3-
methyl-4-difluoromethyl- ~2_1,2,4-triazolin-5-one and
0.07 g (0~0029 mole) of sodium hydride in dimethylform-
amide, and the mixture was heated at reflux temperature
for 3 hours to give 0.62 9 of~ product, mp 117-123~C.
The nmr spectrum was consistent with the proposed
structure.
Ex ~
1-{2,4-DICHI.ORO-5-[2-(1,3-DIOXOLAN-2-YL)ErrHOXYJ-
PHENYL} -3 METHYL-4-DIFL~OROMETHYL-~2-1,2,4-TRI~-
AZOLIN-5-ONE
In the ~anner of Example 4, treatment of 0.75 g
(0.0024 mole) o~ 1-(2,4-dichloro-5-hydroxyphenyl)-3-
methyl-4-difluoromethyl~ 1,2,4-triazolin-5-one with
0.44 9 (0.0026 mole) of 2-(1~3-dioxolan-2-yl)ethyl
bromide in the presence of 0.065 ~ (0.0027 mole) of
sodium hydride and dimethylformamide at reflux tempera-
ture for 3 hours gave 0.6 9 of product, mp 106-109C.
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C15H15Cl2F2N3O4: C 43.92; H 3.69;
N 10.24;
Found: C 46.29; H 4.18;
N 9.66.
Example 8
1-~2,4-DICHLORO-5-(2,2-DIMETHYL-1,3-DIOXOLA~-4-
YLMETHOXY)PHENYL]-3-METHYL-4-DIFLUOROMETHYL- ~2
-1,2~4-TRIAZOLIN-5-ONE _ _
~23~3
- 23 -
In the manner of Example 4, 0.687 g (0.0024 mole) of
2,2-dimethyl-1,3-dioxolan-4-ylmethyl 4-methylphenylsul-
fonate was added to a mixture of 0.75 g (0.0024 mole) of
1-~2,4-dichloro-5-hydroxyphenyl)-3-methyl-4-difluoro-
5 methyl- ~2-1,2,4-triazolin-5 one and 0.072 g 10.003
mole) of sodium hydride in 8 mL of dimethylformamide and
the whole was heated to about 120C over about 2 hours to
give 0.4 g of semi-solid product.
The nmr spectrum was consistent with the proposed
l0 structure.
Example 9
1- {2,4-DICHLORO-5-[3-(2-METHYL-1,3-DIOXOLAN-2
YL)PROPQXY]PHENYL}-3-METHYL-4-DIFLUOROMETHYL- ~2
-1,2,4-TRIAZOLIN-5-ONF
15In the manner of Example 4, the reaction of 0.9 g
(0.003 mole) of 1-(2 t 4-dichloro-5-hydroxyphenyl)-3-methyl-
4-difluoromethyl- ~2-1,2,4-triazolin-S-one with 0.07 g
(0.003 mole) of sodium hydride and 0.48 g (0.003 mole) oE
3-(2-methyl-1,3-dioxolan-2-yl)propyl chloride in the
20 presence of dimethylformamide gave 0.86 g of product, mp
109-1 11 C.
The nmr spectrum was consistent with the proposed
structure.
Example 10
1-(2,4-DICHLORO-S-FURFURYLOXYPHENYL)-3-METHYL-4-
DIFLUOROMETHYL-~_-1,2,4_TRIAZOLIN-5-ONE
Furfuryl bromide was prepared by the method of
Example 21 of U.S. Patent No. 4,282,219 as follows. A
stirred solution of 2.0 g (0.02 mole) of furfuryl alcohol
in 20 mL of diethyl ether was cooled to 5~C, and a
solution of 2.0 g (0.007 mole) of phosphorus tribromide
in 6 mL of diethyl ether was added dropwise over 30
minutes. Upon complete addition, the reaction mixture
was stirred an additional 15 minutes at 5DCo The clear
diethyl ether solution was then decanted from a dark
~36~31
-- 24 --
residue. The clear solution was stirred at 5-SC with
0.5 g of anhydrous potassium carbonate for 10 minutes.
~he solution was decanted away from the potassium car-
bonate and kept cold~ The unstable product, furfuryl
5 bromide, was used as such without delay in the following
reaction.
To a slurry of 1.55 g (0.005 mole) 1-(2,4-dichloro-
5-hydroxyphenyl)-3-methyl-4-difluoromethyl- ~2_1,2,4-
triazolin-5-one and 0.48 g (0.0035 mole~ of potassium
l0 carbonate in 25 mL of acetone, previously cooled to about
8-9C, was added portion wise over about 0.5 hour about 10
mL of the solution of crude furfuryl bromide in diethyl
ether prepared above. The reaction mixture was heated to
about 40C over 3-5 hours, then the remainder of the
15 ether solution of furfuryl bromide was added and heating
at about 40C was continued for about 16 hours. The
reaction mixture was Eiltered, and the Eiltrate washed
sequentially with water, 10% hydrochloric acid, water,
twice with a 10% aqueous solution of sodium hydroxide,
20 and twice with water. The organic layer was dried over
magnesium sulfate, filtered, and the filtrate concen-
trated to give 1.6 g of a dark oily-solid residue. The
residue crystallized upon treatment with petroleum ether,
wgt. 0.91 g, mp 134-135C. A sample for analysis
25 was prepared by recrystall~ization from ethanol, m.p.
135-137C.
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C15Hl 1Cl2F2N3O3: C 46.17; H 2.84;
30N 10.77;
Found: C 46.11; H 2.74;
N 10.11.
Example 11
1- [2, 4-DICHLORO-5- ( 2-THIENYLMETHOXY)PHENYL] -3-
35METHYL-4-DIFLUOROMETHYL-~2-1 ,2 ,4-TRIAZOLIN-5-ONE
- 25 -
In the manner of Example t, the reaction of 0.75 g
(0.0024 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-3-
methyl-4-difluoromethyl- ~2_1,2,4-triazolin-5-one, 0.42
g (0.0024 mole) of 2-thenyl bromide, and 0.1 g (0.004
mole) of sodium hydride in 20 mL of dimethylformamide
5 gave 0.53 g of product, mp 154-155C.
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C15H11Cl2F2N3O3: C 44.35; H 2.73;
N 10~34;
Found: C 44.36; H 2.81;
N 10.02.
Example 12
1-[2,4-~ICHLORO-5-(1,3-DIOXAN-4-YLMETHOXY)PHENYL]-
3-METHYL-4-DIFLUOROMETHYI.- ~ -1,2,4-TRIAZOLIN-
15 5-ONE
In the manner of Example 4, the addition of 0.68 g
(0.005 mole) of 1,3-dioxan-4-ylmethyl chloride to a
previously heated then cooled mixture of 0.75 g (0.0025
mole~ of 1-(2,4-dichloro-5-hydroxyphenyl)-3-methyl-4-di-
20 fluoromethyl- ~2-1,2,4-triazolin-5-one and 0.072 g
(0.003 mole) of sodium hydride in dimethylformamide gave,
after heating at reflux for about 2 hours, 0.2 g of
product as an oil.
The nmr spectrum was consistent with the proposed
25 structure.
Example 13
1-[2,4-DICHLORO-5-(1,4-BENZODIOXAN-2-YLMETHOXY)-
PHENYL~-3-METHYL-4-DIFLUOROMETHYL- ~ -1,2,4-TRI-
AZOLIN-5-ONE
To a solution of 5 g (0.03 mole) of 1,4-benzodi-
oxan-2-methanol in 125 mL of pyridine was added at 0C
6.29 g (0.033 mole) of 4-methylphenylsulfonyl chloride,
and the mixture was stirred for 3 hoursr The reaction
mixture was poured into ice water, and the whole was
- 26 -
e~trac~ed with chloroform. The chloroform layer was
dried over magnesium sulfate, filtered, and the filtrate
concentrated to give an oily residue which solidified
when stirred with water~ The solid product, 1,4-benzo-
dioxan-2-ylmethyl 4-methylphenylsulfonate, was collected
on a filter paper and air dried, mp 73-75C~
In the manner of Example 4, a mixture of 0.5 g
(0.0017 n~ole) of 1-(2,4-dichloro-5-hydroxyphenyl)-3-
methyl-4-difluoromethyl- A2-1,2,4-triazolin-5-one and
l0 0.045 g (0.0019 mole) of sodium hydride in 10 mL of
dimethylformamide was stirred at room temperature for 20
minutes; 0.54 g (0.0017 mole) of 1,4-benzodioxan-2-yl-
methyl 4-methylphenylsulfonate ~as added and the mixture
stirred first at room temperature for 1 hour then at
15 100C for 2 hours to give 0.33 g of product as an oil.
The nmr spectrum was consistent with the proposed
structure.
Example 14
1-[2,4-DICHLORO-5-(TETRAHYDRO-4H-PYRAN-4-YLOXY)-
PHENYL]~3-METHYL-4-DIFLUOROMETHYL- ~ -1,2,4-TRI-
AZOLIN-5-ONE
To a chilled solution of 1.0 g 10.0098 mole) of
tetrahydro-4H-pyran-4-ol in 10 mL of pyridine was added
1.91 g ~0.01 mole) of 4-methylphenylsulfonyl chloride
over 3-5 minutes. The rea~tion mixture was stirred at
about -4C for 15 minutes, then was allowed to stand with
cooling for 16 hours. The reaction mixture was mixed
- with ice-water, and the solid product, tetrahydro-4H-
pyran-4-yl 4-methylphenylsulfonate, collected on a filter
paper, wgt. 1.6 g, mp 56-57C.
In the manner of Example 4, 0.615 g (0.0024 mole) of
tetrahydro-4H-pyran-4-yl 4-methylphenylsulfonate was
added to a previously heated (60C) then cooled (25C)
mixture of 0.75 g (0.0024 mole) of 1-(2,4-dichloro-5-hy-
droxyphenyl)-3-methyl-4-difluoromethyl- ~2-1,2r4-triazo-
~;~36~;3
- 27 -
lin-5-one and 0.065 g (0.0027 ~,ole) of sodium hydride in
8 mL of dimethylformamide, and the mixture was heated at
about 90C for 16 hours to give 0.42 g of product, mp
149-151C.
The nmr spectrum was consistent with the proposed
structure.
Example 15
1-[2,4-DICHLORO-5-(5,6-DIHYDRO--2H-PYRAN~3-YL-
METHOXY)PHENYL]-3-METHYI.-4-DIFLUOROMETHYL- ~2_1,2,4-
TRIAZOLIN-5-ONE
_t~ 5,6-Dihydro-3-hydroxymethyl-2H-pyran
This compound was prepared by the reduction of 14 g
(0.125 mole) of 5,6-dihydro-2H-pyran-3-carbaldehyde with
2.88 g (0.074 mole) of sodium borohydride in a 1:1
mixture of dioxane and water; wgt. 15 g.
Ste~ 2: 5,6-Dihydro-3-chloromethyl-2H-pyran
___ __
Reaction o~ 5 ~ (0,0438 mole) of 5,6-dihydro-3~hy-
droxymethyl-2H-pyran with 11.51 g (0.0448 mole) of
triphenyl phosphine in the presence of 20 mL of carbon
tetrachloride at room temperature for about 40 hours
produced this intermediate as a solid material.
Step 3: 1-[2,4-Dichloro-5-(5,6-dihydro-2H-pyran-3-
ylmethoxy)phenyl]-3-methyl-4-difluoromethyl- ~2-1,2,4-
triazolin-5-one
In the manner of Exampl~e 4, 0.3 g (0.0023 ~ole) of
5,6-dihydro-3-chloromethyl-2H-pyran was added dropwise to
a previously heated (75C) then cooled (25C) mixture of
0.7 g (0.0023 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-
3-methyl-4-difluoron,ethyl- Q2-1,2,4-triazolin-5-one and
0.055 g (0.0023 mole) of sodium hydride in 25 mL of
dimethylformamide, and the mixture was heated to 90C ~or
2 hours then stirred at room temperature for 16 hours and
finally heated at 110C for 1.5 hours to give 0.49 g of
product, mp 143-144C.
The nmr spectrum was consistent with the proposed
~. ~
6~3
- 28 -
structure.
Ex_mple 16
1-[2,4-DICHLO~0-5-(1,3-DIOXOLAN-2-YLMETHOXY)-
PHENYL]~3-METHYL-4-(2-PROPENYL)- ~2-1,2,4-TRI-
AZOLIN-5-ONE
___ _________ ______________ _
In the manner of Example 4, 0.44 g (0.0026 mole) of
1,3-dioxolan-2-ylmethyl bromide was added to a previously
heated (90C) then cooled (25~C) mixture of 0.75 g
(0.0025 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-3-
methyl-~-(2-propenyl)- ~2_1,2,4-triazolin-5-one and 0.07
g (0.0029 mole) of sodium hydride in 10 mL of dimethyl-
formamide, and the mixture was heated at reflux for 2.5
hours to give 0.45 g of product as a waxy solidO
The nmr spectrum was consistent with the proposed
lS structure.
Example 17
1-[2,4-DICHLORO-5-(3-TETRA~I~DROFURANYLOXY)P~ENYL]-
3-METHYL-4-(2-PROPENY~ 2-1,2,4-TRIAZOLIN-5-ONE
In the manner of Example 4, 0.61 g (0.0025 mole) of
3-tetrahydrofuranyl 4-methylphenylsulfonate was added to
a mixture of 0.75 g (0~0025 mole) of 1-(2,4-dichloro-5-
hydroxyphenyl)-3-methyl-4-(2-propenyl)- Q -1,2,4-tri-
azolin-5-one and 0.06 g (0.0025 mole) of sodium hydride
in 30 mL of dimethylformamide, and the mixture was heated
at reflux temperatures for 3~ hours then stirred at room
teMperature for about 64 hours to give 0.7 g of a solid
product. An nmr analysis of the prodwct showed the
reaction had not gone to completion. The crude product
was dissolved in a small amount of diethyl ether, the
solution fil,tered to remove insoluble impurities, and the
filtrate concentrated to give 0.4 g of a solid residue~
The 0.4 g residue was treated with an additional 0.012 g
(0.0005 mole) of sodium hydride and 0.15 g (0.0005 mole)
of 5-hydroxyphenyl compound in dimethylformamide, and the
35 mixture was heated at reflux temperature for 4 hours then
~2~6~
- 29 -
stirred at room temperature for 16 hours to give 0.36 9
of desired product as an oil.
The nmr spectrum was consistent with the proposed
structure.
Example 18
1-[2,4-DICHLORO-5-(3-TETRAHYDROFURANYLOXY)PHENYL]-
3-METHYL-4-n-PROPYL-~2_1,2,4-TRIAZOLIN-5-ONE
In the manner of Example 4, 0.80 g (0.0033 mole~ of
3-tetrahydrofuranyl 4-methylphenylsulfonate was addecl to
l0 a mixture of 1.0 g (0.0033 ~lole) of 1-t2,4-dichloro-5--hy-
droxyphenyl)-3-methyl-4-n-propyl- ~2_1,2,4-triazolin-5-
one and 0.08 g (0.0033 mole) of sodium hydride in di-
methylformamide, and the mixture was heated at 80-90C
for 2 hours, at reflux temperature for 6.5 hours, then
stirred at room temperature for 16 hours and finally
heated at reflux temperature for an additional 5 hours to
give 1.0 y of product as an oil which solidified upon
standing, mp 107-112C. A sample of the product was
recrystallized from ethyl acetate-hexane for analytical
20 purposes, m.p. 116-117C.
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C16H1gCl2N3O3 C 51.63; ~J 5.14;
N 11.29
Found: C 51.55; H 5.11;
N 11.02.
Example 19
1-(2,4-DICHLORO-5-TETRAHYDROFURFURYLOXYPHENYL)-
3-METHYL-4-n-PROPY~-a -1,2,4-TRIAZOLIN-5-ONE
___ __ __ _____ _____________
In the manner of Example 4, 0.49 9 (0.003 mole) of
tetrahydrofurfuryl bromide was added to a mixture of 0.90
9 (0.003 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-3-
methyl-4-n-propyl- ~2-1,2,4-triazolin-5-one and 0.075 9
(0.0031 mole) of sodium hydride in dimethylformamide, and
35 the mixture was heated at 80C for 45 minutes, then
~2~
~ 30 -
stirred at room temperature for 16 hoursr and again
heated (90-100C) for 1 hour. Analysis (TLC) of the
reaction mixture showed the reaction to be incomplete.
Powdered potassium carbonate (0.21 9, 0.0015 mole) and an
additional 0.49 g (0.003 mole) of tetrahydrofurfuryl
bromide were added, and the reaction mixture was heated
at 90-100~C for 2.5 hours, stirred at room temperature
for 16 hours, heated at reflux temperature for 6.5 hours,
stirred at room temperature for 16 hours, and, finally,
heated at reflux for 5 hours to give 0.97 g of product as
a viscous oil.
The nmr spectrum was consistent with the proposed
structure.
Example 20
l-[2~4-DIcHLoRo-5-(2~2-DIMETHyL-l~3~DITHIoLAN-4-yI~-
METHOXY)PHENYL]-3-METHYL-4-DIFLUOROMETHYL- ~ -1,2,4-
TRIAZOLIN-5-ONE
_ . _
Step 1: 2,2-Dimethyl-4-hydroxymethyl-1,3-dithiolan
To a mixture of 10.18 g (0.082 mole) of 2,3-dimer-
capto-1-propanol, 20 mL of cyclohexane, and 5.0 g (G.086
mole) of acetone was added 4 drops of concentrated
hydrochloric acid/ and the mixture was stirred at reflux
temperature for 3.5 hours to give, after fractional
distillation of the reaction mixture, 5.85 g of a color-
less oil, bp 96-106C/1.2-1.5 mm Hg, which solidified on
standing. Recrystallization from toluene-hexane gave
3.96 g of product, mp 45-50C.
Step 2: 4-Chloromethyl-2,2-dimethyl-1,3-dithiolan
To a solution of 3.46 g (0.021 mole) of 2,2-di-
Methyl-4-hydroxymethyl-1,3-dithiolan in 15 mL of toluene
was added dropwise 2.35 9 (0.020 mole) of thionyl chlo-
ride, and the mixture was heated gradually to 80-85C,
maintained at that temperature for 0.75 hour, then
s~irred at room temperature Eor 16 hours. The mixture
was filtered, and the filtrate concentrated to dryness at
~,.
l fii3
- 31 -
60Dc/100 mm Hg to give a residual oil. Distillation of
the oil gave 1.81 y of product, bp 75-78C/1.25-1.35 mm
Hg.
Step 3~ 2,4-Dichloro-5-(2,2-dimethyl-1,3-dithio-
lan-4-ylmethoxy)phenyl]-3-methyl-4-difluoromethyl- ~2_
1,2,4-triazolin-5-one
In the manner of Example 4, 0.493 g (0.0027 mole) of
4-chloromethyl-2,2-dimethyl-1,3-dithiolan was added to a
previously heated (65C) then cooled (25C) mixture of
0.75 g (0.0024 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-
3-methyl-4-difluoromethyl- ~2-1,2,4~triazolin-5-ore and
0.072 g (0.003 mole) of sodium hydride in 8 mL of di-
methylformamide, and the mixture was heated over 3~5
hours to about 100C to give 0.9 g of product as a waxy
solid. Crystallization in the presence of petroleum
ether gave 0.5 g of crystalline product, mp 108--110C.
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C16H~7Cl2F2N3O2S2: C 42.11; H 3.76;
N 9.21;
Found: C 41.89; H 3.62;
N 9.05.
xample 21
1-[2,4-DICHLORO-5-~TETRAHYDRO-4H-THIOPYRAN-4-YLOXY)-
PHENYL]-3-METHYL-4-DIFL~OROMETHYL- ~ -1,2,4-TRIAZO-
LIN-5-ONE
Step 1: Tetrahydro~4H-thiopyran~4-ol
To a stirred solution of 0.8 g (0.021 mole) of
sodiun, borohydride in 30 mL of 1:1 dioxane-water was
30 added a solution of 5.0 g (0.043 mole) of tetrahydro-4H-
thiopyran-4-one in 20 mL of dioxane, and the solution was
stirred at room temperature for 16 hours. The reaction
mixture was concentrated to give a residue which was
dissolved in chloroform and washed with water~ Concen-
35 tra~ion of the chloroform solution gave 4.5 g of product
as an oil which solidified upon standing.
~3~
- 32 -
Step 2: Tetrahydro-4H-thiopyran-4-yl 4-n,ethylphenyl-
sulfonate
To a solution of 4~1 9 (0.015 mole) of tetrahydro-
4H-thiopyran-4-ol in 40 mL of pyridine, cooled in an ice
bath, was added 2.90 9 (0.15 mole) of 4-methylphenylsul-
fonyl chloride, and the reaction mixture was stirred at
room temperature for 16 hours. The mixture was poured
into a mixture of ice and water, and the whole extracted
with diethyl ether. The organic phase was washed with
water then with a 10~ aqueous solution of sodium hydrox-
ide, dried, and concentrated to give 5.8 ~ of product as
an oil.
Step 3: 1-[2,4-Dichloro-5-~tetrahydro-4H-thiopyran-
4-yloxy)phenyl]-3-methyl-4-difluoromethyl- Q -1,2,4-tri-
azolin-5-one
In the manner of Example 4, the reaction of 0.75 9
(0.0024 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-3-
methyl-4-difluoromethyl- ~2-1,2,4-triazolin-5-one, 0.06
g ~0.0025 mole) of sodium hydride, and 0.66 g t0.0024
mole) of tetrahydro-4H-thiopyran-4-yl 4-methylphenylsul-
fonate in dimethylforman.ide gave 0.4 g of product as a
waxy solid.
The nmr spectrum was consistent with the proposed
structure.
Example 22
1-[2,4-DIBROMO-5-(3-TETRAhYDROFURANYLOXY)PHENYL-3-
METHYL-4-DIFLUOROMETHYL-~ -1,2,4-TRIAZOLIN-5-OME
Step 1: 3-Methoxyphenyl hydrazine
A stirred solution of 50.0 g (0.41 mole) of 3-
methoxyaniline in 60 mL of concentrated sulfuric acid and
100 mL, of water was cooled to -5C, and a solution of
28.0 g (0.41 mole) of sodium nitrite in water was added
slowly while maintaining the temperature of the reaction
mixture below 0C. The mixture was stirred at 0C for 1
hour, then added slowly to a chilled, stirred solution of
~6~ Ei;3
- 33 -
100 9 (0.44 mole) of stannous chloride dihydrate in 300
mL of concentrated hydrochloric acid. After complete
addition, the reaction mixture was allowed to warm to
ambient temperature and stand for 16 hours. The reaction
mixture was filtered and the filter cake made basic and
extracted with diethyl ether. The reaction mixture
filtrate was also made basic and extracted with diethyl
ether. The ether extracts were combined and dried with
magnesium sulfate. The mixture was filtered and the
filtrate concentrated under reduced pressure to give 49~1
g of product as an oil.
The nmr spectrum was consistent with the proposed
structure.
Step 2: Pyruvic acid, 3-methoxyphenyl hydrazone.
To a stirred solution of 45 g (0.33 mole) of 3-
methoxyphenyl hydrazine in 400 mL aqueous lN hydrochloric
acid and 400 mL of ethanol was added dropwise a solutio
of 31.5 ~ (0.36 mole) of pyruvic acid in 30 mL of water.
After complete addition, the reaction mixture was stirred
at ambient temperature for 3 hours, and 200 mL of water
was added. The mixture was filtered to give 56 g of
product; mp 113-114C.
The nmr spectrum was consistent with the proposed
structure.
Step 3: 1-(3-Methoxyph~enyl)-3 methyl- ~ -1,2,4-tri-
a~olin-5-one
To a stirred mixture of 55.5 g (0.27 mole) of
pyruvic acid, 3-methoxyphenyl hydrazone in 1500 mL of
toluene was added 27.0 g (0.27 mole) of triethylamine.
The mixture was warmed until a clear solution formed.
Diphenyl phosphoryl azide, 64.8 g (0.27 mole) was added
at 35C, and the reaction mixture was warmed to 75C and
stirred until evolution of nitrogen stopped. The re-
action mixture was heated to reflux temperature and
stirred for 16 hours. The mixture was extracted with
: L23~
- 3~ -
aqueous 10% sodium hydroxide. The extract was washed
with toluene and acidified. The resultant solid was
collected by filtration and air dried to give 36.0 g of
product; mp 143 146C.
The nmr spectrum was consistent with the proposed
structure.
Step 4: 1-(3 Methoxyphenyl)-3 methyl-4-difluoro
methyl-~2-1,2,4-triazolin-5-one
To a stirred solution of 31.0 g (0.15 mole) of
1-(3-methox~phenyl)-3-methyl- ~ -1,2,4-triazolin-5-one,
31.0 9 (0.10 mole) of tetrabutylammoniunl bromide, 31.0 g
(0.77 mole) of sodium hydroxide in 1500 mL of cyclohexane
was added 62.0 g (0.72 mole) of gaseous chlorodifluoro-
methane. The addition caused the reaction mixture to
reflux. After complete addition, the reaction mixture
was cooled. The supernatant liquid was decanted and
washed sequentially with ayueous 10% hydrochloric acid,
water, and a~ueous 10% sodium hydroxide. The organic
layer was dried with magnesium sul~ate and filtered. The
filtrate was concentrated under reduced pressure to give
28.0 g of product as a solid.
The nmr spectrum was consistent with the proposed
structure.
Step 5: 1-(2,4-Dibromo-5-methoxyphenyl)-3-methyl-4-
25 difluoromethyl-~2-1,2,4-tria~olin-5-one
To a stirred solution of 12.0 g (0.047 mole) of
1-(3-methoxyphenyl)-3-methyl-4-difluoromethyl- Q -1,2,4-
triazolin-5-one in 75 mL of acetic acid was added drop-
wise 30.0 g (0.18 mole) of bromine. Upon complete
addition, the reaction mixture was heated at reflux for 6
hours. The reaction mixture was concentrated under
reduced pressure. The residue was dissolved in diethyl
ether and washed with aqueous 10~ sodium thiosulfate and
water. The organic layer was dried with magnesium
sulfate and filtered. The filtrate was concentrated
.~
~23~3
- 35 ~
under reduced pressure to give 17.4 g of product as a
solid~
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C11~gBr2F2N3O2: C 32.00; H 2.20;
N 10~17;
Found: C 31.21; H 1o81;
N 9.28.
Step 6: 1-(2,4-Dibromo-5-hydroxyphenyl)-3-methyl-4-
difluoromethyl-~2-1,2,4-triazolin-5-one
A solution of 17.2 g (0.042 mole) of 1-~2,4-dibromo-
5-methoxyphenyl)-3-methyl-4-difluoromethyl- Q -1,2,4-
triazolin-5-one in 100 mL of methylene chloride was added
dropwise with stirring to 50.6 g (0.20 mole) of boron
15 tribro~nide in methylene chloride. Upon complete addi-
tion, the reaction mixture was stirred at ambient t:emper-
ature for 18 hours. The reac~ion mixture was washe~ wikh
S0 mL of water. The organic layer was separated, dried
with magnesium sulfate, and filtered. The filtrate was
20 concentrated under reduced pressure to give 16.1 g
of product; mp 137-140C.
The nmr spectrum was consistent with the proposed
structure.
Step 7: 1-[2,4-Dibromo-5-(3-tetrahydrofuranyloxy)-
25 phenyl]-3-methyl-4-difluorome~thyl- ~ -1,2,4-trizaolin-5-
one
In the manner of Example 4, the reaction of 1.0 g
tO.0025 mole) of 1-(2,4-dibromo-5-hydroxyphenyl)-3-methyl-
4-difluoromethyl-~2-1,2,4-triazolin-5-one (which may be
30 prepared as described in steps 1-6 above), 0.06 g (0.0025
mole) of sodium hydride, and 0.61 g (0.0025 mole) of
3-tetrahydrofuranyl 4-methylphenylsulfonate (which may be
prepared as described in Example 1, step 1) in dimethyl-
formamide gave 0.95 g of crude product as a solid ma-
35 terial. Treatment with petroleum ether gave 0.83 g of
~3~3
36 -
crystalline product, mp 138-140C~
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C14Hl3Br2F2N3O3: C 35.85; H 2-79;
N 8.96;
Found: C 36.87; H 3O08;
N 9.13.
Example 23
1-(2,4-DIBROMO-5-TETRA8YDROFURFURYLOXYPHENYL~~3-
METHYL-4-DIFLUOROMETHYL-~ -1,2,4-TRIAZOLIN-5~0NE
_
In the manner of Example 4, the reaction of 1.0 g
(0.0025 mole) of 1-(2,4-dibromo-5-hydroxyphenyl)-3-
methyl-4-difluoromethyl- ~2-1,2,4-triazolin-5-one (see
Example 22, step 6), 0.06 g (0.0025 mole) of sodium
15 hydride, and 0.41 g (0.0025 mole) of tetrahydrofurfuryl
bromide in dimethylformamide gave 0.8 g of product as an
oil.
The nmr spectrum was consistent with the proposed
structure.
Example 24
1-[2,4-DICHLORO-5-(3-T~TRAHYDROTHIENYLOXY)PHENYL]-
3-METHYL-4-DIFLUOROMET~YL- ~ -1,2,4-TRIAZOLIN-5-
ONE
Step 1: 3-Tetrahydrothienyl 4-methylphenylsulfonate
To a chilled solution of 1.12 g (0.0098 mole) of
tetrahydrothiophene-3-ol in 15 mL of pyridine was added
1.91 g (0.01 mole) of 4-methylphenylsulfonyl chloride,
and the reaction mixture was stirred in the cold, about
16~C, for 1 hour then placed in a cold refrigerator for
16 hours. The reaction mixture was allowed to warm to
room temperature and was stirred for 1 hour. An addi-
tional 0.3 g (0.0016 mole~ of 4-methylphenylsulfon~l
chloride was added, and the reaction mixture was stirred
at room temperature for 64 hours. The reaction mixture
was poured into water, and the whole was extracted with
.
~23~i3
- 37 -
methylene chloride. The methylene chloride solution was
dried and concentrated to give 1.28 g of product as an
oil.
The nmr spectrum was consistent with the proposed
structure.
Step 2: 1-[2,4-Dichloro-5-(3-tetrahydrothienyloxy)-
phenyl]-3-methyl-4-difluoromethyl- A2-1l2,4-triazolin-5-
one
In the manner of Example 4, 0.644 g (0.0024 mole) of
3-tetrahydrothienyl 4-methylphenylsulfonate was added
to a previously heated (110C) then cooled (25C) mixture
of 0.75 g (0~0024 mole) 1-(2,4-dichloro-5-hydroxyphenyl)-
3-~ethyl-4-difluoromethyl- A -1,2,4-triazolin-S-one and
0.065 g (0.0027 mole) of sodium hydride in 10 mL of
dimethylformanlide, and the mixture was heated over 1.5
hours to 85C, then over 3.5 hours to 135C to give 0.58
g of product, mp 136-140C.
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C14H13Cl2F2N3O2S: C 42.44; ~ 3.31;
N 10.60;
Found: C 43.87; H 3.72;
N 10.08.
Example 25
1-[2,4-DICHLORO-5-(1-OXO-3-TETRAHY~RO-
THIEN~LOXY)PHENYL]-3-MET~YL-4-DIFLUORO-
METHYL-~ -1,2,4-TRIAZOLIN-S-ONE __ _
To a solution of 0.25 g ~0.00063 mole) of 1-[2,4-di-
chloro-5-~3-tetrahydrothienyloxy)phenyl]-3-methyl-4-di-
30 fluoromethyl-~2-1,2,4-triazolin-5-one (Example 24) in 4
mL of glacial acetic acid was added 0.06 mL (0.0007 mole)
of a 30% aqueous solution of hydrogen peroxide, and the
reaction mixture was stirred at room temperature for 16
hours. The reaction mixture was concentrated to a moist
solid residue which upon treatment with water gave 0.16 g
~36~3
- 38 -
of desired product, mp 183-186DC.
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C14H13Cl2F2N3O3S: C 40.7g; H 3-18;
N 10 19;
Found: C 41.77; H 3D50;
N 9.68.
Example 26
1-[2,4-DICHLORO-5-(1,1-DIOXO-3-TETRAHYDROTHIENYLOXY)-
PHENYL]-3-METHYL-4-DIFLUOROMETHYL-~2 1,2,4-
TRIAZOLIN-5-ONE
A mixture of 0.1 g t0.00025 mole) of 1-[2~4-dichloro-
5-(3-tetrahydrothienyloxy)phenyl]-3-methyl-4-diEluoro-
methyl- ~2-1,2,4-triazolin-5-one IExample 24), 0.10 mL
(0.00116 mole) of a 30~ aqueous solution of hydrogen
peroxide, and 2 mL of glacial acetic acid was heated at
56C for 3 ho~rs. l'he reaction mi~ture was concentrated
to a waxy solid which upon treatment with water gave 0.06
g of product, mp 201-203C.
Elemental and nmr analyses were conducted on samples
of the same product produced in a second run of this
reaction.
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C14H13Cl2F2N3O4S: C 39~27; H 3.06;
N 9.81;
Found: C 39.16; H 3.18;
N 9.66.
Example 27
1-[2,4-DICHLORO-5-(2,2-DIMETHYL-1,1,3,3-TETRAOXO-
- 1,3-DITHIOLAN-4-YLMETHOXY)PHENYL]-3-METHYL~4-
DIFLUOROMETHYL- ~ -1,2,4-TRIAZOLIN-5-ONE
____________ ____________________
To a solution of 0.18 g (0.0004 mole) of 1-[2,4-di-
chloro-5-(2,2-dimethyl-1,3-dithiolan-4-ylmethoxy)phenyl]-
3-methyl-4-difluoromethyl- ~2-1,2,4-triazolin-5-one
~6~
- 39 -
(Example 20) in 4 mL of glacial acetic acid was added
0.15 mL (0.0017 mole~ of a 30% aqueous sol~tion of
hydrogen peroxide, and tne reaction mixture was stirred
at roo~ temperature for 15 minutes, then heated at
5 reflux for 15 minutes, and finally stirred again at room
tempera-ture for 16 hours. An additional 0.10 mI, (0.0012
mole) of 30% hydrogen peroxide solution was added, and
the reaction mixture was heated to reflux for about 1
hour. The reaction mixture was diluted with water and
l0 the product was collected on a filter paper, 0.21 g, mp
>184C (cloudy).
The nmr spectrum was consistent with the proposed
structure.
Analysis calcd for C16H17Cl2F2N3O6S2: C 36.93; H 3 29;
N 8.08;
Found: C 35.38; H 3.24;
7.54.
xample 28
-
1-[2-CHLORO-4-METHYL-5-(TETRAHY~RO-4H-
T~IOPYRAN-4-YLOXY)PHENYL]-3-METHYL-4-
DIELuoRoMETHyL-Q2-1~2t4-TRIAz~LIN-5-oNE
Step 1. 4-Methyl-3-methoxyphenyl hydrazine.
The compound was prepared by a n,ethod analogous to
that of Example 22, Step 1. The reaction of 100 g (0.73
25 mole) of 4-methyl-3-methoxyan~iline and 50.5 g (0.73 mole)
of sodium nitrite in the presence of 330 g (1.46 moles)
of stannous chloride dihydrate, 1160 mL of concentrated
hydrochloric acid and 250 mL of water gave 58.0 g of
product as an oil.
The nmr spectrum was consistent with the proposed
structure.
Step 2- Pyruvic acid, 4-methyl-3-methoxyphenyl
hydrazone.
This compound was prepared by a method analogous to
35 that of Example 22, Step 2. The reaction of 57.6 g
,
,
~3~ 3
- 40 -
(0.378 mole) of 4-methyl-3-methoxyphenyl hydrazine and
33.3 g ~0.378 mole) of pyruvic acid in the presence of
400 mL of IN hydrochloric acid and 400 mL of ethanol gave
59.0 g of product as a solid.
The nmr spectrum was consistent with the proposed
structure.
Step 3: 1-(4-Methyl-3-methoxyphenyl)-3 methyl-
-1,2,4-triazolin-5-one.
This compound was prepared by a method analogous to
that of Fxan,ple 22, Step 3. The reaction of 56.8 y
(0.256 mole) of pyruvic acid, 4-methyl-3-methoxyphenyl
hydrazone and 70.3 g (0.256 mole) of diphenyl phosphoryl
azide in the presence of 25.9 g (0.256 mole) of trie~h-
ylamine in 1500 mL of toluene gave 75.0 g of damp pro(luct;
15 mp 165-168C.
The nmr spectrum was consistent with the proposed
structure.
Step 4: 1-(4-Methyl-3-methoxyphenyl)-3-methyl-4-di-
fluoromethyl-Q -1,2,4-triazolin-5-one.
This compound was prepared by a method analogous to
that of Example 22, Step 4. The reaction of 60.0 g
(0.276 mole~ of 1-(4-methyl-3-methoxyphenyl)-3-methyl-
a2-1,2,4-triazolin-5-one and 60.0 g (0.67 mole) of
chlorodifluoromethane in the presence of 60.0 g (1.5
25 moles) of sodium hydroxide~ and 60.0 g (0.186 mole)
tetrabutylammonium bromide in 2000 mL of cyclohexane gave
18.5 g of product as a solid.
The nmr spectrum was consistent with the proposed
structure.
Step 5: 1-(2-Chloro-4-methyl-5-methoxyphenyl)-3-
methyl-4-difluoromethyl-a2-1,2,4-tria2olin-5-one.
A solution of 15.0 g (0.056 mole) of 1-(4-methyl-3-
methoxyphenyl)-3-methyl-4-difluoromethyl- a 2_1~2,4_tri_
azolin-5-one and 7.5 g (0.056 mole) of sulfuryl chloride
in 100 mL of chloroform was stirred at ambient tempera-
~r
~2~ i3
- 41 -
ture for 2 hours. The reaction mixture was concentrated
under reduced pressure to give a residue. The residue
was dissolved in methylene chloride and washed with
aqueous 10~ sodium hydroxide. The organic layer was
dried with magnesium sulfate and Eiltered. The filtrate
was concentrated under reduced pressure to give 16.5 g of
product as a solid.
The nmr spectrum was consistent with the proposed
structure.
Step 6. 1-(2-Chloro-4-methyl-5-hydroxyphenyl~-3-
methyl-4-difluoromethyl-~ -1,2,4-triazolin-5-one.
This compound was prepared by a method analo~ous to
that of Example 22, Step 6. The reaction of 16.0 g
(0.053 mole) of 1-~2-chloro-4-methyl-5-methoxyphenyl)-3-
15 nlethyl-4-difluoromethyl-~2-1,2,4-triazolin-5-one and
39.6 g (0.158 mole) of boron tribromide in 100 nlL oP
methylene chloride gave 10.5 g of product as a solid.
The nmr spectrum was consistent with the proposed
structure.
Step 7: 1-[2-Chloro-4-methyl-5-(tetrahydro-4H-
thiopyran-4-yloxy)phenyl]-3-methyl-4-difluoromethyl-
-1,2,4-triazolin-5-one.
In the manner of Example 4, the reaction of 0.66 g
(0.0023 mole) of 1-(2-chloro-4-methyl-5-hyaroxyphenyl)-3-
methyl-~-difluoromethyl- ~ 2,4-triazolin-5-one ~which
may be prepared as described in steps 1-6 above), 0.055 g
(0.0023 mole) of so~ium hydride, and 0.55 g (0.0020 mole)
of tetrahydro-4H-thiopyran-4-yl 4-methylphenylsulfonate
in 25 mL of dimethylformamide gave 0.75 g of product as
an oil.
The nmr spectrum was consistent with the proposed
structure.
Example 29
1-[2,4-DIBROMO-5~ METHYL-3-PYRROLIDINYLOXY)PHENYL]-
3-METHYL-4-DIFLUOROMETHYL-~ -1,2,4-TRIAZOLIN-5-ONE
_
~,3~i3
Step 1: 1-Methy1-3-pyrrolidinyl 4-methylphenylsul-
fonate
To a mixture of 3.0 g (0.03 mole) of 3-hydroxy-1-
methylpyrrolidine, 3.1 g (0.03 mole) of triethylamine,
and 25 mL of methylene chloride was added 5.6 9 (0.03
n,ole) of 4-methylphenylsulfonyl chloride, and the reaction
mixture was stirred at room temperature for 3 hours. The
reaction mixture was concentrated to a residue. The
residue was dissolved in ether, the solution filtered,
and the filtrate concentrated to give 5.75 g of product
as an oil.
The nmr spectrum was consistent with the proposed
structure.
Step 2: 1-[2,4-Dibromo--5-(1-methyl-3-pyrrolidinyl-
lS oxy)phenyl]-3-methyl-4-difluoromethyl- ~2-1,2~-triazo-
lin-5-one
In the manner of Example 4, the reaction of 0~75 g
(0.0019 mole) of 1-(2,4-dibromo-S-hydroxyphenyl)-3-methyl-
4-difluoromethyl- Q2-1,2,4-triazolin-S-one (Example 22,
step 6), 0.05 g (0.0019 mole) of sodium hydride, and 0.48
g (0.0019 mole) of 1-methyl-3-pyrrolidinyl 4-methylphenyl-
sulfonate in 25 mL of dimethylformamide gave 0.58 g of
product as an oil.
The nmr spectrum was consistent with the proposed
structure.
Example 30
1-[2-BROMO-4-METHYL-5 (3-TETRAHYDROFURANYLOXY)-
PHENYL]-3-METHYL-4-DIPLUOROMF.THYL- Q -1,2,4-TRI-
AZOLIN-5-ONE _ _
Step 1: 1-(2-Bromo-4-methyl-5-methoxyphenyl)-3-
methyl-4-difluoromethyl-~2-1,2,4-triazolin-S-one
A solution of 2.0 g (0.007 mole) of 1-(4-methyl-3-
methoxyphenyl)-3-methyl-4-difluoromethyl- ~2-1,2,4-tri-
azolin-5-one (which may be prepared as described in
35 Example 28, step 4) and 1.5 9 (0.009 mole) of bromine in
~3~
-- 43 --
50 ml of acetic acid was stirre~ at ambient temperature
for 18 hours. The acetic acid was ren,oved under reduced
pressure, and the residue dissolved in methylene chloride
The solution was washed with aqueous 10~ sodium bisulfate
The organic layer was dried with magnesium sulfate and
filtered. The filtrate was concentrated under reduced
pressure to give 2.4 g of product as a solid; n,p 132-
134C.
The nmr spectrum was consistent with the proposed
structure.
Step 2: 1-(2-Bromo-4-methyl-5-hydroxyphenyl)-3-
methyl-4-difluoromethyl-~2-1,2,4-triazolin-5-one
To a stirred solution of 2.1 g (0.006 mole) of
1-(2-bromo-4-methyl-5-methoxyphenyl)-3-methyl-4-difluoro-
methyl- ~2-1,2,4-triazolin-S-one in 30 mL of methylene
chlorine at ambient temperature was added 4.4 9 (0.01~
mole) of boron tribromide. Upon complete addition, the
reaction mixture was stirred at ambient temperature for
18 hours. Water, 25 mL, was stirred into the reaction
mixture. The layers were separated, and the organic
layer dried with magnesium sulfate. The mixture was
filtered, and the filtrate concentrated to give 1.5 g of
product, mp 143-144C.
The nmr spectrum was consistent with the proposed
structure.
Step 3: 1-[2-Bromo-4-methyl-5-(3-tetrahydrofuranyl-
oxy)phenyl] -3-methyl-4-difluoromethyl- ~2-1,2,4-triazo-
lin-5-one
In the manner of Exan,ple 4, the reaction of 0.5 y
(0.0015 mole) of 1-(2-bromo-4-methyl-5-hydroxyphenyl)-3-
methyl-4-difluoromethyl- ~2 1,2,4-triazolin-5-one, 0.036
g (0.0015 mole) of sodium hydride, and 0.36 g (0.0015
mole) of 3-tetrahydrofuranyl 4-methylphenylsulfonate
(which may be prepared as described in Example 1,
35 step 1) in 20 mL of dimethylformamide gave 0.46 g of
~3~
- ~4 -
product as an oil.
The nmr spectrum was consistent with the proposed
structure.
~xample 31
1-[2,4-DICHLORO-5-(1-METHYL-3-~YRROLIDINYLOXY)-
PHENYL]-3-METHYL-4-DIFLUOROMETHYI.- ~ -1,2,4-TRI-
AZOLIN-5-ONE _ _
In the manner of Example 4, the reaction of 0.75 g
(0.00t9 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-3-
meth~l-4-difluoromethyl- a -1 ,2,4-triazolin-5-one, 0.046
g (0.0019 mole) of sodium hydride, and 0.49 g (0.0019
mole) of 1-methyl-3-pyrrolidinyl 4-methylphenylsulfonate
(Example 29, step 1) in 30 mL of dimethylformamide gave
0.4 g of product as an oil.
The nmr spectrum was consistent with the proposed
structure.
_xample 32
1-[2-CHLORO-4-METHYL-5-(3-TETR~HYDROFURANYLOXY)-
PHENYL]-3 METHYL-4-DIFLUOROME'rEJYL-~ -1,2,4-
TRIAZOLIN-5-ONE
In the manner of Example 4, the reaction of 0.8 g
t0.0028 mole) of 1-(2-chloro-4-methyl-5-hydroxyphenyl)-3-
methyl-4-difluoromethyl- ~2_1,2,4-triazolin-5-one (which
may be prepared as described in Example 28, steps 1-6),
0.07 g (0.002g mole) of sodium hydride,~and 0.67 g
(0.0028 mole) of 3-tetrahydrofuranyl 4-methylphenylsul-
fonate (which may be prepared as described in Example 1,
step 1) in dimethylformamide gave 0.75 g of product
as an oil.
The nmr spectrum was consistent with the proposed
structure.
Example 33
1-(2-CHLORO-4-METHYL-5-TETRAHY~ROFURFURYLOXYPHENYL)
3 METHYL-4-DIFLUOROMETHYL-~2-1,2,4-TRIAZOLIN-5-ONE
In the manner of Example 4, the reaction of 0.8 g
:,
~23~3
- ~5 -
(0.0028 mole) of 1-(2-chloro-4-methyl-5-hydroxyphenyl)-3-
methyl-4-difluoromethyl- ~ 2,4-triazolin-5-one (which
may be prepared as described in Example 28, steps 1-6)~
0.07 g (0.0029 mole) of sodium hydride, and 0.46 g
(0.0028 mole) of tetrahydrofurfuryl bromide in dimethyl-
formamide gave 0.47 g of product as an oiil.
The nmr spectrum was consistent with the proposed
structure.
Example 34
1-[2,4-DICHLVRO-5-(1,1-DIOXOTETRAHYDRO-4H-
THIOPYkAN-4-YLOXY)PHENYL]-3 MET~YL-4-
DIFL~OROMETHYL-
A mixture of 0.34 g (0.00083 mole) of 1-[2,4-di-
chloro-5-(tetrahydro-4H-thiopyran-4-yloxy)phenyl]-3-
methyl-4-difluoromethyl- a2-1,2r4-triazolin-5-one
(Example 21), 10 mL (0.116 mole) of a 30~ aqueous solu-
tion of hydrogen pero~ide~ and 25 mL oE glacial acekic
acid was heated at reflux tenlperature for 3 hours. ~'he
reaction mixture was concentrated to a residue. The
residue was dissolved in methylene chloride and washed
with a 10% aqueous solution of sodium hydroxide~ The
methylene chloride layer was dried and concentrated to
give 0.25 g of product as an oil.
The nmr spectrum was consistent with the pro~osed
structure.
Example 35
1-~2,4-DICHLORG-5-(3-TETRAHYDROFURANYL~XY)-
PHENYL]-3-CHLORO-4-(2-PROPENYL)- ~ -1,2,4-
TRIAZOLIN-5-ONE _
In the manner of Example 41 the reaction of 1.8 g
t0.0056 mole) of 1-(2 r 4-dichloro-5-hydroxyphenyl)-3-
chloro-4-(2-propenyl)- ~ -1,2,4-triazolin-5-one, 0.15 g
(0.0062 mole) of sodium hydride, and 1.49 g ~0.0062 mole)
of 3-tetrahydrofuranyl 4-methylphenylsulfonate (which may
35 be prepared as described in Example 1, step 1) in 11 mL
. =
~2~
- ~6 -
of dimethylformamide gave, after recrystallization from
heptane-ethyl acetate~ 1~1 g of product, mp 137 1 3a c.
The nmr spectrum was consistent with the proposed
structure~
Example 36
1-[2,4-DICHLORO-5-(3-TETRAHYDRO~U.RANYLOXY)-
PHENYL]-3-ETHYL-4-DIFLUOROMETHYL-~2-1,2,4-
TRIAZOLIN-5-ONE
_
This compound was prepared by a method similar to
that of Example 1. The reaction of 0.63 9 (0.0019 mole)
of 1-(2,4-dichloro-5-hydroxyphenyl)-3-ethyl-4-difluoro-
methyl- Q2-1,2,4-triazolin-5-one with 0.47 g (0.0019
mole) of 3-tetrahydrofuranyl 4-methylphenylsulfonate, in
the presence of 0.048 g (0.002 mole) of sodi~m hydride
and 5 mL of dimethylformamide gave 0.57 g of product mp
115-118~C.
The nmr spectrum wa~ consistent with the proposed
structure.
The intermediate 1-(2,4-dichloro-5-hydroxyphenyl)-
3-ethyl-4-difluoromethyl- ~2-1~2,4-triazolin-5-one may
be prepared by a method similar to that of Example 38
(steps 1-6) below starting with 2,4-dichlorophenol and
proceeding via the intermediates 2,4-dichloro-5-(1-
methylethoxy)aniline (step 1), 2,4-dichloro-5-~1-methyl-
ethoxy)phenylhydrazine (step 2), 2-ketobutyric acid
2,4-dichloro-5-~1-methylethoxy)phenylhydrazone (step 3~
- use 2-ketobutyric acid rath~r than pyruvic acid, 1-
[2,4-dichloro-5-(1-methylethox~)phenyll-3-ethyl - ~2_
1,2,4-triazolin-5-one (step 4), and 1-12,4-dichloro-5-
(1-methylethoxy)phenyl]-3-ethyl~4-difluoromethyl-
a -1 ,2,4-triazolin-5-one.
Example 37
1-[2,4-DICHLORO-5-(3-TETRAHYDROFURANYLOXY)-
PHENYL]-3-(l,l-DIMETHYLETHYL)-4-DIFLUORO-
METHYL-~2o1,2,4-TRIAZOLIN-5-ONE
6~
- 47 -
Step 1: 1 (3-Methoxyphenyl)-3-(1,1-dimethyl-
ethyl~ 1,2,4-triazolin 5-one
3-Methoxyphenylhydrazine, prepared from 10.0 g
~0.0573 mole) of the hydrochloride salt by treatment
with potassium carbonate in the presence of water and
xylene, was reacted with 10.4 g (0.06 mole) of ethyl
pivaloylcarbamate in the presence of 1.5 g of phos-
phorus pentoxide in xylene to give 3.84 g of product.
The nmr spectrum was consistent with the pro-
posed structure.
Step 2: 1-(3-Methoxyphenyl)-3-(1,1-dimethyl-
ethyl)-4-difluoromethyl-~ -1,2,4-triazolin-5-one
The reaction of 3.87 g (0.01565 mole) of 1-(3-
methoxyphenyl)-3-(1,1-dimethylethyl)-~ 1,2,4-trlazo-
lin-5-one wi-th an excess of chlorodifluoromethane in
-the presence oE 4 g oE sodium hyclroxide, 4 g oE tetra~
butylammonium bromide, 220 mL oE cyclohexane, and 10
mL of tetrahydrofuran gave 3.64 g of product as an oil.
The nmr spectrum was consistent with the proposed
structure.
Step 3: 1-(2,4-Dichloro-5-methoxyphenyl)-3-
(l,l-dimethylethyl)-4-difluoromethyl-~ -1,2,4-triazo-
lin-5-one
The 3~methoxyphenyl product from step 2 (3.21 g,
0.0108 mole) was treated with 10 mL of sulfuryl chlor-
ide to give 2.83 g of the 2,4~dichloro-5-methoxyphenyl
product, mp 129-132C.
The nmr spectrum was consistent with the proposed
structure.
Step 4: 1-(2,4-Dichloro-5-hydroxyphenyl)-3-
(l,l-dimethylethyl)-4-difluoromethyl-A -1,2,4-triazo-
lin-5-one
Trea-tment of 2.47 g (0.00675 mole) of 1-(2,4-di-
chloro-5-methoxyphenyl)-3-(1,1-dimethylethyl)-4-di-
fluoromethyl-~2-1,2,4-triazolin-5-one with 20 mL of a
1.0 molar solution of boron tribromide in methylene
~3~3
- 48 -
chloride (0.0202 mole of BBr3) yave 2.02 g of product,
mp 133-136C.
The nmr spectrum was consistent with the proposed
structure.
Step 5: 1-[2,4-Dichloro-5-(3 tetrahydrofuranyl-
oxy)phenyl]-3-(1,1-dimethylethyl)-4-difluoromethyl-~2-
1,2,4-triazolin-5-one
This compound was prepared by a method similar
to that of Example 1. The reaction of 0.5 g (0.0014
mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-3-(1,1-di-
methylethyl)-4-difluoromethyl-~2-1,2,4-t:riazolin-5-one
with 0.34 g (0.0014 mole) of 3-tetrahydrofuranyl 4-
methylphenylsulfonate in the presence of 0.036 g (0.0015
mole) of sodium hydride and 5 mL of dimethylformamide
gave 0.42 g of product as an oil.
The nmr spectrum was consistent wi-th the proposed
struckure.
F~
1-[4-CE-]LORO-2-FLUORO-5-(3-TETRAHYDROFURAN-
YLOXY)PHENYL]-3-METHYL-4-DIFLUOROMETHYL-A -
1,2,4-TRIAZOLIN-5-ONE
Step 1: 4-Chloro-2-fluoro-5-methoxyaniline
The intermediate 4-chloro-2-fluoro-5-methoxyaniline
was prepared from commercially available 2-chloro-4-fluor-
ophenol as detailed by E. Nagano, et al. in European Pat-
ent Application 69,855.
Step 2: 4-Chloro-2-fluoro-5-methoxyphenylhydra-
zine
A stirred solution of 48.0 g (0.27 mole) of 4-
chloro-2-fluoro-5-methoxyaniline in 500 mL of concen-
trated hydrochloric acid was cooled to -5C and 23.5 g
(0.34 mole) of sodium nitrite in 100 mL of water was
added dropwise. After complete addition, the reaction
mixture was stirred at 0C for one hour. A second
solution of 154.0 g (0.68 mole~ of stannous chloride in
~6~3
- 49 -
225 mL of concentra~ed hydrochloric acid was cooled to
0C, and the cold diazonium solution prepared above was
added to it slowly. After complete addition, the reac-
tion mixture was allowed to warm to ambient temperature.
The reaction mixture was filtered to collect a solid.
This solid was dissolved in an aqueous 50% sodium hy-
droxide solution, and the solution extracted with tolu-
ene. The toluene extract was dried with magnesium
sulfate and filtered. The filtrate was concentrated
under reduced pressure to yield 22.4 g of 4-chloro-2-
fluoro-5-methoxyphenylhydrazine as a solid.
The nmr spectrum was consistent with the proposed
structure.
Step 3: Pyruvic acid, 4-chloro-2-fluoro-5 meth-
oxyphenylhydrazone
~ stirred solution of 21.0 g ~0.11 mole) of 4-
chloro-2-fluoro-5-methoxyphenylhydrazine and lO0 mL of
aqueous 10% hydrochloric acid in 100 mL of ethanol was
warmed to 40C, and a solution of 10.0 g (0.114 mole) of
pyruvic acid in 20 mL of water was added. Upon comp~ete
addition, the reaction mixture was stirred for one hour.
An additional 50 mL of water was added and the reaction
mixture filtered to collect a solid. The solid was air
dried to yield 29.0 g of pyruvic acid, 4-chloro-2-fluoro~
25 5-methoxyphenylhydrazone; mp~166-196r'C.
The nmr spectrum was consistent with the proposed
structure.
Step 4: 1-(4-Chloro-2-fluoro-5-methoxyphenyl)-
3-methyl-A -1,2,4-triazolin-5-one
A stirred solution of 27.0 g (0.104 mole) of pyru-
vic acid, 4-chloro-2-fluoro-5-methoxyphenylhydrazone,
29.0 g (0.105 mole) of diphenylphosphoryl azide, and
11.0 g (0.108 mole) of triethylamine in 500 ~IL of toluene
was heated under reflux for four hours. The reaction
mixture was cooled to ambient temperature an~ extracted
with an a~ueous 10% sodium hydroxide solution. rrhe
~36~
- 50 -
extract was neutralized with gaseous carbon dioxide, and
a solid was collected by filtration. The solid was air
dried to yield 11.0 g of 1-(4-chloro-2-fluoro-5-~ethoxy-
phenyl)-3-methyl- ~ -1,2,4-triazolin-5-one, mp 193-
195C.
The nmr spectrum was consistent with the proposed
structure.
Step 5: 1-(4-Chloro-2-fluoro-5-methoxyphenyl-
3-methyl-4-difluoromethyl- ~ -1,2,4-triazolin-5-one
lO A stirred mixture of 10.0 g (0.039 mole) of 1-
(4-chloro-2-fluoro-5-methoxyphenyl)-3-methyl- ~2_1,2,4-
triazolin-5-one, 10.0 g (0.031 mole) of tetrabutyl-
ammonium bromide and 10.0 g (4.25 mole) of sodium hy-
droxide in 250 mL of cyclohexane was warmed to 60C~
C~llorodifluoromethane, 10.0 9 (0.12 mole) was bubbled
into the reaction mixture. After complete addition, the
reaction mixture was warmed to reflux and stirred for one
hour. The hot solution was decanted from a pot residue
and cooled to ambient temperature. Methylene chloride
was added to the cooled mixture to dissolve a solid
precipitate. The mixture was washed with 10~ hydro-
chloric acid, then with an aqueous 10% sodium hydroxide
solution. The organic layer was dried with anhydrous
magnesium sulfate and filtered. The filtrate was concen-
trated under reduced pressure to yield 5.0 g of 1-(4-
chloro-2-fluoro-5-methoxyphenyl)-3-methyl-4-difluoro-
methyl-Q2-1,2,4-triazolin-5-one; mp 86-88C.
- The nmr spectrum was consistent with the proposed
structure.
Step 6: 1-(4-Chloro-2-fluoro-5-hydroxyphenyl)-
3-methyl-4-difluoromethyl- ~ -1,2,4-triazolin-5-one
A stirred solution of 4.6 g (0.015 mole) of 1-(4-
chloro-2-fluoro 5-methoxyphenyl)-3-methyl-4-difluoro-
methyl- ~2-1,2,4-triazolin-5-one in 200 mL of methylene
chloride was cool~d to 10C, and a solution of 11.2 9
(0.045 mole) of boron tribromide in 45 mL of methylene
- 51 -
chloride was added. ~pon complete addition, the reaction
mixture was stirred for four hours as it warmed to
ambient temperature. After this time 100 mL of water was
added, and the reaction mixture continued to stir for an
additional 18 hours. The organic layer was separated,
dried with anhydrous magnesium sulfate, and filtered.
The filtrate was concentrated under reduced press~re to
yield 4.4 g of 1-(4-chloro-2-fluoro-5-hydroxyyhenyl)-4-
difluoromethyl-3-methyl-~2_1,2,4-triazolin-5-one; mp
147-152C.
The nmr spectrum was consistent with the proposed
structure.
Step 7: 1-[4-Chloro-2 fluoro-5-(3-tetrahydro-
furanyloxy)phenyl]-3-methyl-4-difluoromethyl- ~ -1,2,4-
triazolin-5-one
This compound was prepared by the method similar to
that of Example 1. The reaction of 0.7 g (0.00238 mole)
of 1-(4-chloro-2-fluoro-5-hydroxyphenyl)-3-methyl-4-di-
fluoromethyl- ~2-1,2,4-triazolin-5-one (which may be
prepared as described in steps 1-6 above) with 0.6 g
(0.00247 mole) of 3-tetrahydrofuranyl 4-methylphenyl-
sulfonate in the presence of 0.06 g (0.00247 mole) of
sodium hydride and 30 mL of dimet~ylformamide gave 0.54 g
of product as an oil.
The nmr spectrum was consistent with the proposed
structure.
Example 39
1-(4-CHLORO-2-FLUORO-5-TETRAHYDROFURFURYL-
OXYPHENYL)-3-METHYL-4-DIFLUOROMETHYL- a -
1,2,4-lR~A~oLlN 5 ON~ _
This compound was prepared by the reaction of 0.7 g
(0.00238 mole) of 1-(4-chloro-2-fluoro-5-hydroxyphenyl)-
3-methyl-4-difluoromethyl- ~2-1,2,4-triazolin-5-one
with 0.4 g (0.00242 mole) of tetrahydrofurfuryl bromide
35 in the presence of 0.06 9 (0.00247 mole) of sodium
hydride and 30 mL of dimethylformamide; yield, 0.25 g as
63
- 52 -
an oil.
The nmr spectrum was consistent with the proposed
structure.
HERBICIDAL ACTIVITY
The test species ~sed in demonstrating the herbi-
cidal activity of compounds of this invention include
cotton ~Gossypium hirsutum var. Stoneville), soybean
(Glycine max var. Williams), field corn (Zea mays var.
Agway 595S), rice (Oryza sativa var. Labelle), wheat
(Triticum aestiviwn var. Prodax), field bindweed (Convol-
vulus arvensis), morningglory (Ipomea lacuno _ or Ipomea
hederacea), velvetleaf (Abutilon theophrasti~, barnyard-
grass (Echinochloa crus galli), green foxtail (Setaria
viridis), johnsongrass (Sorghum halepense~, and yellow
nutsedge (Cyperus esculentus).
Procedure-
-
Two disposable fiber flats (8 cm x 15 cm x 25 cm)
for each rate of application for each candidate herbicide
for preemergence testin~ were filled to an approximate
aepth of 6.5 cm with steam sterilized sandy loam soil.
The soil was leveled and impressed with a template to
provide six evenly spaced furrows 13 cm long and 0.5 cm
deep in each flat. Seeds or tubers of cotton, soybean,
corn, rice, wheat, and yellow nutsedge were planted in
the furrows of the first flat, and seeds of bindweed,
morningglory, velvetleaf, barnyardgrass, green foxtail,
and johnsongrass were planted in the furrows of the
second flat. The six-row template was again employed to
firmly press the seeds or tubers into place. A topping
soil of equal portions of sand and sandy loam soil was
placed uniformly on top of each flat to a depth f
approximatel~ 0.5 cm~ Flats for postemergence testing
were prepared in the same manner.
The flats for the preemergence test were first
watered, then drenched with a solution of test compound
as described below. The flats were placed in a green
~36~
- 53 -
house and watered regularly at the soil surface for 21
days at which time phytotoxicity data were recorded.
The flats for the postemergence test were placed in
a greenhouse and watered for 8-10 days, then the foliage
of the emerged test plants was sprayed with a solution of
the test compound. ~fter spraying, the foliage was kept
dry for 24 hours, then watered regularly for 21 days, and
phytotoxicity data recorded.
In both preemergence and postemergence tests, the
candidate herbicides were applied as aqueous-acetone
solutions at rates equivalent to 8.0 kilograms/hectare
(kg/ha) and submultiples thereof, i.e., 4.0 kg~ha, 2.0
kg/ha, and so on. Preemergence applications were made as
soil drenches using 100 mL of test solution of appropriate
concentration for each of the two flats/cornpound.
Postemergence applications were ~ade as foliag~ sprays
using 5 mL of test solution for each o~ the two flats.
For flats of the size described above, an applica-
tion rate of 8.Q kg/ha of test compound is equivalent to
0.025 g/flat. A stock solution of 0.2 g of test compound
in 40 mL of acetone containing 0.5~ v/v of sorbitan
monolaurate emulsiier/solubilizer was prepared. For the
8.0 kg/ha preemergence test, 10 mL of the stock solution
was diluted with water to give 200 mL of test solution
for application as a soil d~rench to both flats for the
compound, 100 mL/flat. For the 8.0 kg/ha postemergence
test, 10 nlL of the stock solution was used undiluted as a
spray, 5 mL/flat. The remaining 20 mL of stock solution
was diluted with an equal volume of acetone-emulsifier to
give 40 mL of a second stock solution, containing 0.1 g
of test compound, and the process abo~e repeated, i.e.,
20 mL of the solution being used for the 4.0 kg/ha
application rate, and 20 mL for the preparation of lower
rate tes~ solutions by the same process.
Herbicidal data at selected application rates are
given for various compounds of the invention in the
~36~3
- 54 -
tables below. I'he test compounds are identified in the
tables below by numbers which correspond to those in
Table 1 above.
~3~ ii3
- 55 -
Table 2
Preemergence Herbicidal Activity [4 000 kg/haL
Compound No
% Xill at 40000 k~/ha
S~ecies 1 2 3 4 5 6
Cotton 100 50 0 70 20 100
Soybean 100 0 100 60 50 100
Field Corn 100 10G100 100 60 100
Rice 100 100 80 1OG O 100
Wheat 100 10G100 100 100 100
Field Bindweed100 100100 100 100 100
Morningglory 100 100100 90 100 100
Velvetleaf 100100'100 100 100 100
Barnyardgrass 100 lOO100 100 90 tOO
Green Foxtail 100 lOO100 100 100 lOO
Johnsongrass 100 100100 100 100 100
Yellow ~ut~edge 100 60 0 0 0 90
Species 7 8 9 10 11 12
Cotton 90 70 30 0 0 20
Soybean 100 100 0 0 0 100
Field Corn 100 100 30 0 30 100
Rice 70 ~70 40 20 0 100
Wheat 100 100 80 40 20 100
Field Bindweed100 100100 100 0 100
Morningglory 100 100 90 70 40 90
Velvetleaf lOO 100100 100 100 100
Barnyardgrass 100 100100 90 100 100
Green Foxtail 100 100100 100 100 100
Johnsongrass 100 100100 100 100 100
Yellow Nutsedge 70 20 0 0 0 30
- 56 -
Table 2
(Continued)
~ Id No
_ _ _ _
% Kill at 4.000 k~/ha __
Species __ _ 13 14 _15 16 17 18
Cotton 090 020 60 70
Soybean 0 100 60 60 100 lO0
Field Corn 0 100 100 100 10d 100
Rice 0 lO0 100 90 90 90
Wheat 0 100 100 100 lO0 100
Field Bindweed90 100 lO0 50 80 70
Morningglory 0 100 90 60 95 90
Velvetleaf 100 100 lO0 100 lO0 100
Barnyardgrass 0 lO0 100 lO0 lO0 lO0
Green Foxtail lO0 lO0 lO0 lO0 lO0 lO0
Johnsongrass 0lO0 100 lO0 lO0 lO0
Yellow Nutsedge 0 lO0 20 0 95 ~0
Species 19 20 21 22 23 _ 24
Cotton 0 60lO0 60 0 lO0
Soybean 0 80100 100 0 100
Field Corn 90 60lO0 lO0 lO0 100
Rice 20 ~0lO0 lO0 40 100
Wheat lO0lO0 100 100 95 100
Field Bindweed 0 lO0 lO0 80 0 lO0
Morningglory 20 lO0 lO0 90 0 lO0
Velvetleaf 100100 100 100 100 100
Barnyardgrass 50 100 lO0 100 100 100
Green Foxtail 90 lO0 100 lO0 100 100
Johnsongrass 30 100 100 100 100 tO0
Yellow Nutsedge 0 0 100 80 0 100
~3~3
- 57 -
Table 2
(Continued)
Compound No
~ Kill at 4.000 kg/ha
S ecies 25 26 27 28 29 30
Cotton 100 100 0 0 080
Soybean 100 100 0 0 0 0
Field Corn 100 100 0 100 0 100
Rice 100 100 0 10 0 100
Wheat 100 100 0 0 0 100
Field Bindweed100 100 0 70 0 100
Morningglory 100 100 0 0 0 60
Velvetleaf 100 100 ~100100 0 100
Barnyardgrass 100 lO0 0 90 40 100
Green Foxtail lO0 lO0lO0 100 95 100
Johnsongrass 100 lO0 0 90 S0 lO0
Yellow NutsedgelO0 lO0 0 0 0 90
S ecies 31 32 33 34 35
P _ _ __.
Cotton 0 30 0 0 0
Soybean 0 60 60 50 lO0
Field Corn 100100 100 30 30
Rice 1001~00 80 0 100
Wheat 100lO0 100 100 100
Field Bindweed 80 100 20 0 80
Morningglory 20 100 90 0 100
Velvetleaf 100100 100 90 100
Barnyardgrass 100100 100 0 100
Green Foxtail 100100 100 95 100
Johnsongrass 100100 100 30 100
Yellow Nutsedge 0 100 0 0 50
~23~
- 58 -
I'able 3
Preemergence Herbicidal Activity [0.250 kg/ha~
Compound No
% Kill at 0.250 kg/ha
Species 1 2 3 4 5 6
_
Cotton 30 0 0 0 0 0
Soybean 30 0 0 0 0 0
Field Corn 100 100 0 35 0 0
Rice 90 0 - 20 Q 60
Wheat 100 10 - 30 0 80
Field Bindweed20 90 0 0 0 0
Morningglory 60 40 0 0 0 0
Velvetleaf 100 100 ' 20100 80100
Barnyardgrass100 100 0100 0 70
Green Foxtail100 lO0 0100 0lO0
JohnsongrasslO0 lO0 50 80 0lO0
Yellow Nutsedge 80 50 0 0 0 0
S ecies 7 8 9 10 11 12
P _ . _ _ _
Cotton 0 0 0 0 0 0
Soybean 0 0 0 0 0 0
Field Corn 80 95 30 0 0 30
Rice 10 ~ 0 0 0 0 30
Wheat 40 20 0 30 0 50
Field Bindweed0 10 0 0 0 0
Morningglory 0 20 0 0 0 0
Velvetleaf lO0 100 50 80 10100
Barnyardgrass100 80 0 0 0100
Green Foxtail100 100 95100 100100
Johnsongrass 95 70 20 0 70 90
Yellow Nutsedge 50 0 0 0 0 0
~2~ 3
- 59 -
Table 3
(Continued)
_ Com~ound No _ _
% Kill at 0.:250 kg/ha
_
S ecies 13 14 15 16 17 18
P
Cotton 0 0 0
Soybean 0 0
Field Corn 0 100 60 0 70 30
Rice 0 95 50 0 20 0
Wheat 0 lO0 90 0 95 90
Field Bindweed0 0 0 0 0 0
Morningglory 0 0 0 0 0 0
Velvetleaf 0 90 ' 30 0 90 100
Barnyardgrass 0 100 30 0 40 30
Green Foxtail100 90 100 10 40 0
Johnsongrass 0 100 80 20 40 60
Yellow Nutsedge 0 0 0 0 0 0
S ecies 19 20 21 22 23 24
p
Cotton 0 0 0 0 0 0
Soybean 0 0 20 0 0 0
Field Corn 0 .060 100 0 60
Rice 0 ~0 0 0 0 60
Wheat 0 0 0 0 0 30
Field Bindweed0 0 0 a 0 60
Morningglory 0 0 0 0 0 0
Velvetleaf 0 70 50 80 0 90
Barnyardgrass 0 0 20 100 50 20
Green Foxtail 0 40 g5 100 100 100
Johnsongrass 0 50 95 100 90 80
Yellow Nutsedge 0 0
~31&fl~3
- 60 -
Table 3
(Continued)
Com~ound No
% Kill at 0.250 kg/ha
Species 25 26 27 28 29 30
Cotton 0 0 0 0 0 0
Soybean 0 80 0 0 0 0
Field Corn 100 100 0 0 030
Rice 80 40 0 0 0 0
Wheat 90 95 0 0 0
Field Bindweed50100 0 0 0 0
Morningglory 0 70 0 0 0 0
Velvetleaf 90 100 0 0 070
Barnyardgrass8n 95 0 0 040
Green Foxtail95 100 050 090
Johnsongrass 30 95 0 0 050
Yellow Nutsedge 0 0 0 0 0 0
Species 31 32 _3 _ 34 35
Cotton 0
Soybean 0
Field Corn 0 60 60 0 0
Rice ~50 0
Wheat n 50 0 0 100
FieId Bindweed0 0 0 0 0
Morningglory 0 0 0 0 0
Velvetleaf 0 90 0 0 100
Barnyardgrass 0 100 20 0 100
Green Foxtail 0 100 0 0 90
Johnsongrass 0 100 40 0 95
Yellow Nutsedge 0 0 0 0 0
,. . .
~36~
- 61 -
Table 4
Preemergence Herbicidal Activity [2 000 kg/ha]
_ Compound No
% Kill at 2.000 k~/ha
Species 36 37 38 39
Cotton 0 0 100 80
Soybean 0 0 100 100
Field Corn 100 0 100 100
Rice 100 0 100 100
Wheat 100 0 100 100
Field Bindweed 100 0 100 100
Morningglory 90 0 100 100
Velvetleaf 100 0 100 100
Barnyardgrass 100 10 100 100
Green Foxtail lO0 lO0 100 100
Johnsongrass 100 20 lO0 lO0
Yellow Nutsedge 80 0 lO0 lQ0
. Table 5
Postemergence Herbicidal Activity [4.000 kg/ha]
Compound No
~ Kill at 4.000 kg/ha
Species 1 ~2 _ 3 4 5
Cotton lO080 90 lO0 20 60
Soybean 70 0 0 0 0 40
Field Corn 10030 0 0 0 50
Rice 10020 0 0 0 100
Wheat 10040 60 0 0 60
Field Bindweed10030 30 40 0 100
Morningglory 10090 40 20 3-0 90
Velvetleaf 100100 100 100 90 100
Barnyardgrass 10050 95 30 0 90
Green Foxtail 10060 20 30 30 100
Johnsongrass 10060 50 40 40 90
Yellow Nutsedge 80 0 0 0 0 40
.-
~36~
- ~2 -
Table 5
(Continued)
Compound No
% Kill at 4.000 kg/ha
S~ecies 7 8 9 10 17 12
'
Cotton 95 100100 10 60 100
Soybean 0 20 0 0 0 70
Field Corn 90 70 0 0 0 100
Rice 60 70 0 0 0 100
Wheat 70 80 0 0 0 95
Field Bindweed80 95 0 50 0 100
Morningglory100 100,50 40 0 100
Velvetleaf 100 100100 100 100 100
Barnyardgrass95 10020 0 0 100
Green Foxtail100 10070 50 30 100
Johnsongrass 70 95 40 0 0 100
Yellow Nutsedge 60 95 0 0 0 10
S ecies 13 14 15 16 17 18
P
Cotton 100 100100 100 80 80
Soybean 0 100 0 0 0 60
Field Corn 0 100100 60 100 100
Rice 0 10080 95 95 70
Wheat 0 100100 lO0 100 100
Field Bindweed100 10090 80 80 70
Morningglory 10 10090 100 100 80
Velvetleaf 100 100100 100 100 100
Barnyardgrass 0 100100 90 100 100
Green Foxtail100 100100 50 100 100
Johnsongrass 0 100100 95 100 100
Yellow Nutsedge 0 0 0 0 50 50
~36
- 63 -
Table 5
(Continued)
_ Compound No
~ Kill at 4.000 kg~ha
Species 19 20 ~1 22 23 24
Cotton 50 80 100 100 40100
Soybean 0 80 100 0 0 50
Field Corn 0 30 100 60 0100
Rice 0 0 100 90 10 80
Wheat 30 lO0 100 100 30 95
Field Bindweed 0 90 100 100 100 100
Morningglory 40 80 1 100 90 10100
Velvetleaf 90 100 100 100 90100
Barnyardgrass 40 0 100 100 10 90
G~a~ ~Y~a.~ ~ a~ ~oo ~oo so~ OO
Yei~ ~o~ ~;17u~ e
species z~ 27 28 2.. 30
~tt~n 100 2û ~0 70 8
Soybean 20 0 ~ ~ 0
Field Corn 1 00 0 0 O 0
Rice 90 0 ~) o 70
Wheat 1OO 0 80 0 20
Fleld Blndweed 1 t~0 n sn a 80
Morningglory 100 0 10 70 80
Velvetleaf 100 80 100 30 so
Barnyardgrass 100 0 0 0 95
Green Foxtail 100 80 100 95 100
Johnsongrass 100 0 70 0 100
Yellow Nutsedge 90 0 0 0 0
- 6~ -
Table 5
(Continued)
Compound No
% Kill at 4 000 ky/ha
Species 31 3233 _ 34 35
Cotton 100 10080 60 100
Soybean 30 20 0 0 0
Field Corn 0 100100 0 0
Rice 20 10020 0 0
Wheat 0 100100 40 100
Field Bindweed60 100100 80 0
~orningglory 40 100100 50 0
Velvetleaf 100 10.0100 100 100
Barnyardgrass 0 10095 0 100
Green Foxtail100 100100 0 90
Johnsongrass 0 100100 0 100
yellGw Nutsedge0 100 0 0 0
Table 6
Postemergence Herbicidal Act vity [2.000 kg/ha]
Com ound No
P
% Kill at 2.000 kg/ha
Species 36 37 38 39
Cotton 100 0 lOû 100
Soybean 0 0 90 90
Field Corn 60 0 100 100
Rice 95 Q 100 100
Wheat 100 0 100 100
Field Bindweed 90 70 100 100
M~rningglory 100 50 100 100
Velvetleaf 100 0 100 100
Barnyardgrass 90 Q 100 100
Green Foxtail 100 - 100 100
Johnsongrass 100 0 100 100
Yellow Nutsedge 0 0 100 100
~36~
- 65 -
It is clear that the generic class of aryltria-
zolinones and sulfur analoas thereof described and
illustrated herein is characterized by herbicidal acti-
vity, and that the degree of this activity varies among
specific compounds within this class and to some extent
among the species of plant to which these compounds may
be applied. Thus, selection of a specific herbicidal
compound for control of a specific plant may readily be
made.
For herbicidal applications, the active compounds
as above defined are formulated into herbicidal composi-
tions, by admixture, in herbicidally effective amounts,
with the adiuvants and carriers normally employed for
facilitating the dispersion of active ingredients for the
particular utility desired, recognizing the fact that the
~ormulation and mode of application of a toxicant may
affect the activity of the material in a given applica-
tion. Thus, these active herbicidal compounds may be
formulated as granules of relatively large particle size,
as water-soluble or water-dispersible granules, as
powdery dusts, as wettable powders, as emulsifiable
concentrates, as solutions or as any of several other
known types of formulations, depending on the desired
mode of application~
For preemergence a~plication these herbicidal
compositions are usually applied either as sprays,
dusts, or granules in the area in which suppression of
vegetation is deslred. For postemergence control of
established plant growth, sprays or dusts are most
commonly used. These formulations may contain as
little as 0.5% to as much as 95% or more by weight of
active ingredient.
Dusts are free flowing admixtures of the active
ingredient with finely divided solids such as talc,
natural clays, kieselguhr, flours such as walnut shell
and cottonseed flours, and other organic and inorganic
,
~236~
- 66 -
solids which act as dispersants and carriers for the
toxicant; these finely divided soli~s have an average
particle size of less than about 50 microns. A typical
dust formulation, useful herein, is one containing 1.0
5 part of the herbicidal compound and '39.0 parts of talc.
Wettable powders, also useful formulations for both
pre- and postemergence herbicides, are in the form of
finely divided particles which disperse readily in water
or other dispersant. The wettable powder is ultimately
10 applied to the soil either as a dry dust or as an
emulsion in water or other liquid. Typical carriers for
wettable powders include Fuller's earth, kaolin clays,
silicas, and other highly absorbent, readily wet inor-
ganic diluents. Wettable powders normally are prepared
15 to contain about 5-80% o~ active ingredient, depending
on the absorbency of the carrier, and usually also
contain a small amount o~ a wetting, dispersing or
emulsifying agent to facilitate dispersion. For exam-
ple, a useful wettable powder formulation contains 80.8
20 parts of the herbicidal compound, 17.9 parts of Palmetto
clay, and 1.0 part of sodium lignosulfonate and 0.3 part
of sulfonated aliphatic polyester as wetting agents.
Frequently, additional wetting agent and/or oil will be
added to the tank mix for postemergence application to
25 facilitate dispersion on t~e foliage and absorption by
the plant.
Other useful ~ormulations for herbicidal applica-
tions are emulsifiable concentrates, which are homo-
geneous liquid or paste compositions which are dispersi-
30 ble in water or other dispersant, and may consistentirely o~ the herbicidal compound and a liquid or solid
emulsifyin~ agent, o~ may also contain a liquid carrier,
such as xylene, heavy aromatic naphthas, isopharone, and
other non-volatile organic solvents. For herbicidal
35application these concentrates are dispersed in water or
other liquid carrier, and normally applied as a spray to
~2~
- 67 -
the area to be treated. Ihe percentage by weight bf the
essential active ingredient may vary according to the
manner in which the composition is to be applied, but in
general comprises 0.5 to 95~ of active ingredient by
weight of the herbicidal composition.
Typical wetting, dispersing or emulsifying agents
used in agricultural formulations include, for example,
the alkyl and alkylaryl sulfonates and sulfates and
their sodium salts; polyhydric alcohols; and other types
of surface active agents, many of which are available in
commerce. The surface active agent, when used, normally
comprises from 1~ to 15~ by weight of the herbicidal
composition.
Other useful formulations for herbicidal applica-
tions include simple solutions of the active ingredientin a dispersant in which it is completely soluble at the
desired concentration, such as acetone , alkylated
naphthalenes, xylene or other organic solvents. Granu-
lar formulations, wherein the toxicant is carried on
relatively coarse particles, are of particular utility
for aerial distribution or for penetration of cover crop
canopy. Pressurized sprays, typically aerosols wherein
the active ingredient is dispersed in finely divided
form as a result of vaporization of a low boiling dis-
persant sol~ent carrier, such as the Freons, may alsobe used. ~ater-soluble or water-dispersible granules are
also useful formulations for herbicidal application of
the present compounds. Such granular formulations are
free-flowing, non-dusty, and readily water-soluble or
water-miscible. The soluble or dispersible granular
formulations described in U.S. patent ~o. 3,920,442 are
useful herein with the present herbicidal compounds.
The active herbicidal compounds of this in~ention
may be formulated and/or applied with insecticides,
fungicides~ nematocides, plant growth regulators,
fertilizers, and other agricultural chemicals a~d may
~23~
- 6~ -
be used as effective soil sterilants as well as herbi-
cidally. In applying an active compound of this inven-
tion, whether formulated alone or with other agricul-
tural chemicals, an effective amount and concentration
of the compound is of course employed~
