Note: Descriptions are shown in the official language in which they were submitted.
lZ~iiZ~i8
01 -1- 61936-1612
HER~3ICI DAL 5-AMINO-3-OXO-4--t ~;IJ13~;TITUTED-PHENYL)-
2, 3-DIHYDROFURAN AND DERIVATIVES TIIERI~:OF' _
05
ACKGROUND OF THE INVEN'rION
This invention relates to 5-amino-3-oxo-4-
~substituted-phenyl)-2,3-dihydro~uran derivatives and to
the use of such compounds as herbicides and plant growth
regulators.
Chemiker-Zeitung 10~ (1980) No. 10,
Pages 302-303, is an academic paper disclosing the ring
closure of l-(dimethylamino)-2,4-diphenyl-1-buten-3,4-
dione to yield 5-dimethylamino-2,4-diphenyl-2,3-dihydro-
furan. British Patent No. 1,521,092, discloses certain
3-phenyl-5-substituted-4(1H)-pyrid-ones or -thiones as
herbicides. Japanese Patent Application 13,710/69
(Chemical Abstracts 71:61195e) discloses the generLc
formula for 5-amino-3-oxo-4-~phenyl and halophenyl)-2,3-
dihydrofuran and specifically discloses 5-amino-3-oxo-4-
(phenyl and 4-chlorophenyl)-2,3-dihydro~urans. Japanese
Patent No. 19090 (Chernical Abstracts 69P10352e) discloses
certain 2,3-dihydrothiophenes as phanmaceuticals.
Helvetica Chemica Acta, Volume 56, Pages 362-378 (1383)
discloses 5-N-cyclopropyl-4-phenyl-2-methoxycarbonyl-
methylene-3-furanone as part of an academic chemical
synthesis discussion. U.S. Patent No. 4,441,910 discloses
herbicidal ureidosulfonylfurans and ureidosulfonylthio-
phenes.
SUMtlARY OE THE INVENTION
The uresent invention provides compounds having
both pre-emergence and post-emergence herbicidal activity
and having especially good pre-emergence activity ayainst
a broad spectrum of both broad-leaf weeds and grassy
weeds. At lower application rates the compounds also
exhibit plant growth regulatiny properties.
~,~
.
~z~
-2- 61936-1612
The compounds of the present invent.ion can be re-
presented by the following formula:
Y ~\ , O
1/
(I)
wherein R is lower alkyl having l through 4 carbon
atoms; cycloalkyl having 3 through 7 carbon atoms, lower
alkenyl; haloalkyl having l through 4 carbon atoms and l
through 3 halo atoms independently selected from the group
of fluoro, chloro, bromo or iodo; haloalkenyl having 2
through 4 carbon atoms and l through 3 halo atoms inde-
pendently selected from the group of fluoro, chloro,
bromo, or iodo; lower alkoxyalkyl wherein the alkoxy and
alkyl moiety thereof independently have l through 3 carbon
atoms; lower alkylthioalkyl wherein the alkyl moieties
independently have l through 3 carbon atoms; phenyl,
naphth-l-yl, inden-l-yl; 4-fluorophenyl; arylalkylene
having l through 3 carbon atoms in the alkylene moiety and
wherein said aryl moiety is phenyl, naphth-l-yl or inden-
l-yl; or substituted aryl or arylalkylene selected from
the group having the formulas:
R~ R5 R4 R5
-(R3) ~ ; (R ). ~
R7 R6 R9 ~ - R ; or
,~
. ,~, .
~S;~4~t3
01 -3- 61g36-1612
R4 RS
05
-(R3)
~R6
R8 \R7
wherein one, two or three of R4, R5, R6,
R7, R8, and R9 are independently selected from
the group of lower alkyl, lower alkoxy, halo,
nitro, or haloalkyl having 1 through 3 carbon
atoms and 1 through 3 of the same or different
halo atoms, and the remainder are hydrogen; and
R3 is a single bond or an alkylene having 1
through 3 carbon atoms;
Rl is hydrogen or alkyl having 1 through 4
carbon atoms;
R2 is hydroyen, allcyl having 1 through 4 carbon
atoms, alkenyl having 3 or 4 carbon atoms, alkoxy-
carbonylalkyl having from 1 through 4 carbon atoms in
the alkoxy moiety and from 1 through 4.carbon atoms
in the alkyl moiety all<oxyalkyl wherein the alkoxy
and alkyl moieties independently have 1 through 3
carbon atoms or alkylthioalkyl wherein the alkyl
moieties independently have 1 through 3 carbon atoms;
or
Rl and R2 toyether with the nitrogen to which
they are joined for~.a saturated or unsaturated
- nitroyen heterocycle haviny from 4 through 6 ring
atoms one of which is nitrogen and the remainder of
which are carbon atoms;
X is hydroyen, lower alkyl, lower alkoxy, halo,
or trifluoromethyl and can be at any available posi-
tion on the phenyl ring; and Y is lower alkyl, lower
alkoxy; halo; lower haloalkyl having 1 through 4
~2~
01 -4-
carbon atoms and 1 to 3 of the same or different halo
atoms; lower haloalkoxy having 1 through 4 carbon
05 atoms and 1 through 3 of the same or different halo
atoms; or lower haloalkylthio having 1 through 4
carbon atoms and 1 through 3 of the same or different
halo atoms; with the proviso that when Y is halo then
R, Rl and R2 are not all hydrogen and the further
proviso that when Y is other than trifluoromethyl and
X is other than hydrogen, and Rl is hydroyen and R2
is hydrogen then R is methyl, ethyl, propyl, 2-halo-
phenyl, 2-lower alkylphenyl or 4-fluorophenyl.
The invention also comprises compatible salts of
the compound oE Formula (I), for example salts obtained
via replacement of the amino hydrogen ~i.e., Rl and R2 is
hydrogen) with a compatible cation or enolation of the 3-
oxo group following replacement of the amino hydrogen.
The compounds of Formula (I) exist as keto <_>
enol isomers. The compounds also have an asymmetric
carbon atom and can also exist as optical isomers. In
some instances the compounds also exist as geometric
isomers. The above formula is intended to encompass the
respective individual isomers as well as mixtures thereof
and the respective isomers as well as mixtures thereof are
encompassed within the invention.
It has also been discovered that the presence o~
a 3-trifluoromethyl substituent on the 4-phenyl group of
the compounds of the present invention gen0rally very
substantially enhances herbicidal activity.
In a further aspect the inven-tion provides a
herbicidal composition comprising a compatible carrier and
a herbicidally effective amount of the compounds of
Formula (I), or compatible salts thereof, or mixtures
thereof.
The present invention also provides a method for
preventing or controlling the growth of unwanted vegeta-
tion, which comprises treating the growth medium and/or
lZ~ k~3
01 -5-
the foliage of such veyetation with a herbicidally effec-
tive amount of the compound(s) of Formula (I) and/or
05 compatible salts thereof.
In another aspect, the present invention pro-
vides a plant growth regulating composition comprising a
compatible carrier and a plant growth regulating amount of
the compound of Formula (I), compatible salts of
Formula (I), or mixtures thereof, effective to alter the
normal growth pattern of said plants~
The present invention also provides a method for
regulating plant growth which comprises treating ths
growth medium and/or the foliage of such vegetation with a
plant yrowth regulating effective amount of the com-
pound(s) of Formula (I) and/or compatible salts thereof,
! effective to alter the normal growth pattern of said
plants.
The present invention also provides chemical
intermediates and processes for preparing the compounds of
Formula (I).
The invention will be ~urther described herein-
below.
FURTH~R DESCXIPTION OF THE
INVENTION AND THE PREFERRED EMBODIME~TS
Illustrations of typical compounds of
Formula (I) of the prasent invention can be had by refer-
ence to Examples 2, 3, 6-10 set forth hereinbelow on Pages
24-30 and 33-51. In terms of substituents, the preferred
compounds are those wherein R is lower alkyl, aryl or
substituted aryl, more preferably methyl, ethyl, propyl,
phenyl or substituted phenyl, and especially phenyl,
monomethylphenyl or monohalophenyl, more especially
methyl, ethyl, n-propyl, 2-halophenyl, 2-lower
alkylphenyl, or 4-fluorophenyl; Rl and R2 are inde-
pendently hydrogen, methyl, ethyl or n-propyl, and more
preferably one of Rl or R2 is hydrogen and the other is
hydrogen, methyl, ethyl or n-propyl, preferably hydrogen~
methyl or ethyl, especially methyl; X is hydrogen and/or Y
is 3-trifluoromethyl or 3-halo, especially 3-
i8
01 -6-
trifluoromethyl. Most preferably the compounds contain a
combination of two or more preferred substituents.
05 The compounds of Formula (I) wherein Rl and R2
are each hydrogen and R is aryl or substituted aryl can be
conveniently prepared by the following schematically
represented process:
X X
Y CHCCH2Z' > Y , ~
CN H2N o Z'
(A) (I')
wherein X and Y are as defined hereinabove;
and Z' is aryl, or substituted aryl.
Rearrangement of Compound (A) to Compound (I')
can be conveniently effected by contacting Compound (~)
with a halogen, preferably bromine, and a liquid carboxy-
lic acid in the presence of an inert organic solvent.
Typically, this process is conducted at tempera-
tures in the range of about from 0 to 1~0C, preferably
about from 20 to 30C, for about from 4 to 36 hours,
preferably about from 18 to 24 hours, using about from 1.0
to 10.0, preferably 1.0 to 1.1 moles of halogen per mole
of Compound (A). Suitable liquid carboxylic acids which
can be used include, for example, acetic acid, propionic
acid, butyric acid, formic acid, and the like. By using
excess carboxylic acid, the excess can serve as solvent or
liquid carrier for this reaction system. Other organic
solvents which can be used include, for example, liquid
halogenated alkanes, for example, methylene chloride,
carbon tetrachloride, chloroform, 1,2-dichloroethane;
liquid aromatics, for example, benzene, toluene; liquid
alkyl ethers, for example, diethylether, dimethyl,
sulfoxide, dimethylforamide, and the like, and compatible
mixtures thereof.
s~
01 ~7~
Best results are obtained using bromine as the
halogen, although chlorine and iodine could also be used.
05 The starting materials OL Formula (A) can be
prepared by the following schematically represented
process:
r~
CH2CN + Z'-CH2-C-ORl - > (A)
(C)
wherein Rl is lower alkyl, aryl (e.g. phenyl) or
arylalkylene (e.g. benzyl), and Z', Y and X are as
defined hereinabove.
This process can be conveniently effected by
contacting Compound (B) with Compound (C), and a strong
base, preferably in an inert organic solvent.
Typically, this process is conducted at tempera-
tures in the range of about from 0 to 100C, preferably
75 to 85C, for about from 5 to 36 hours, preferably 18 to
24 hours, using about from 1.0 to 10.0, preferably 1.0 to
1.2 moles of Compound (C) per mole of Compound (s).
Typically, about from 1.0 to 10.0 moles of base are used
per mole of Compound (C).
Suitable strong bases which can be used include,
for example, alkali metal alkanolates, for example, sodium
methoxide, sodium ethoxide, potassium ethoxide, sodium
hydride, potassium hydride, and the like. The s~rong base
should preferably be one which does not yield water as a
by-product in this reaction system.
Suitable inert solvents which can be used
include, for example, lower alkanols (for axample,
methanol, ethanol, and propanol) tetrahydrofuran,
dimethoxyethane, dioxane, and the like, and compatible
mixtures thereof. Conveniently, the alkali metal
alkanolate is prepared in situ by reacting an alkali metal
'l'h~
01 -8- 61936-1612
with excess alkanol which in turn serves as solvent for
the above reaction.
05 The starting materials of Formulas (8) and tC)
are generally known materials and can be prepared by known
procedures, or obvious modifications thereof (i.e.,
substitution of appropriate startin~ materials), The
preparation of Compound (B) is for example described in
Org. Syn. Coll., Volume l, 107 (1941), and the preparation
of Compound (C) is described in Ory. Syn. Coll., Volume l,
270 (1941).
The compounds of Formula ~I) wherein Rl and R2
are each hydrogen can be prepared via the general process
schematically represented by the followin~ overall
reaction e~uation:
r :H2CN + R-C-C-OR5 - > ~ ~ + R5OH
~B) (E) t
wherein R, and X and Y are as defined
hereinabove; and R5 is lower alkyl, aryl (e.g.
phenyl) or arylalkylene te.g. hen~yl).
This process can be conveniently effected by
contacting Compound (B) with Compound (E), and a strony
base (e.g. sodium methoxide, sodium ethoxide), preferably
in an inert organic solvent.
Typically, this process is conducted at ~empera-
tures in the ranye of about from 0 to 100C, preEerably 75
to 85C for about from 5 to 3G hours, preferably 18 to
2~ hours, using about from 1.0 to 10.0, preferably l.0 to
l.2 moles of Compound (E) per mole of Compound (B~.
Suitable inert organic solvents which can be used include,
~or example, lower allcanols (e.g. methanol, ethanol,
~0
9 1 ~
propanol, etc.); tetrahydrofuran; dimethoxyethane, dioxane; and
the like, and compatible mixtures thereof.
Suitable bases which can be used for this process
include those bases previously described with respect to the
reaction of Compound (B) with Compound (C).
The hydroxy esters of formula (E) are generally known
compounds and can be prepared by known procedures or by obvious
modi~ications thereof (e.g., by using appropriately substituted
starting materials).
The compounds of Formula I wherein Rl and R2 are
hydrogen and R is alkyl, cycloalkyl, alkoxy, alkoxyalkyl,
alkylthioalkyl, arylalkylene, substituted arylalkylene or
alkenylalkyl (e.g., _CH2CH=CH) can also be conveniently
prepared by the following schematically represented process:
/~CHC-CHR' ' ' ~ cyclizing agent -~
y CN OR ~
O
H2N R'~
(I''')
wherein R''' is alkyl, cycloalkyl, alkoxyalkyl, alkoxy,
alkylthioalkyl, arylalkylene, substituted arylalkylene or
alkenyl and R10 is lower alkyl, preferably methyl.
This process can be conveniently effected by contact-
ing Compound (A') with a cyclizing agent, under reactiveconditions, preferably in an inert organic solvent.
01 -10~
Typically, this process is conducted at tempera-
tures in the range of about from 0 to 200C, preferably
05 about from 115 to 120C, for about from 10 to 120 minutes,
preferably about from 10 to 30 minutes, using about from 1
to 10, preferably 1 to 2, moles of cyclizing agent per
mole of Compound (A'). Suitable cyclizing agents which
can be used include, for example, strong anhydrous acids,
for example, sulfuric acid, hydrogen chloride, hydrogen
bromide, trifluoroacetic acid, methane sulfonic acid, and
the like. Best results are typically obtained using
anhydrous sulfuric acid. Suitable inert organic solvents
which can be used include, for example, acetic acid,
propionic acid, butyric acid, toluene, xylene, and the
like, and compati~le mixtures thereof.
The starting materials of formula (A') can be
prepared via the following schematically represented
process:
X X
CHCH2OR10 _ > Ç ~ C - C-CH2R10
CN CN O
y y
(B' ) / (B' ' )
/
X L /
~ eM+ ~
C - C - CH - OR10 R~X~ ~ (A')
_/ I e~M '
C N
(B' ' ' )
wherein R''' and R10 are as defined hereinabove;
X' is chloro, bromo or iodo and M and M' are
independently sodium or lithium.
~ Z~ i8
0 1
Although this process is schematically shown as
three steps, the steps are typically and conveniently
o5 conducted in situ. Also as is conventional with such
reactions the reactions are preferably conducted under
substantially anhydrous condition under an inert gas
(e.g., nitrogen).
In the first step of this process compound (B')
is contacted with a non-nucleophilic base, preferably in
an inert organic solvent. This step is typically
conducted at temperatures in the range of about from
0-25C for about from 1/2 to 3 hours using about from 1 to
2, preferably 1 to 1.3, mole e~uivalents of non-nucleo-
philic base per mole of compound (B'). Suitable non-
nucleophilic bases which can be used include, for example,
alkali metal hydrides, e.g., sodium hydride, potassium
hydride, etc.; alkali metal amides, e.g., lithium
bis(trimethylsilyl)amide; sodium bis(trimethylsilyl)amide;
potassium bis(trimethylsilyl)amide; lithium diethylamide,
lithium diisopropyl amide; sodium dimethylamide, and the
like. Sodium hydride is generally preferred as it has
given very good results and is readily commercially
available. The alkali metal amides, and also of course
the alkali metal hydrides, are generally known compounds
and can be prepared by known procedures, or obvious
modifications thereof. For example, the alkali metal
amides can be prepared by the reaction of a secondary
amine with an alkyl alkali metal.
Suitable inert organic solvents, which can be
used, include, for example, tetrahydrofuran, dioxane,
dimethoxyethane, diethyl ether, diisopropyl ether, and the
like and compatible mixtures thereof.
The second step can be effected by contacting
compound (B'') with an alkyl base preferably in an inert
organic solvent. As before noted, this process step is
preferably conducted in situ with the reaction product
mixture of the first step. Typically the second step is
conducted at temperature ranges of about from -78 to 0C
for about from 1 to 4 hours using about from 1 to 2,
01 -12-
preferably 1 to 1.3 mole equivalents of alkyl base per
mole o~ compound (B''). Suitable alkyl bases which can be
05 used include for example alkyl-alkali metals, alkyl
Grignard reagents, and the like. Preferably n-butyl-
lithium is used as it gives good results and is readily
commercially available. Suitable solvents which can be
used include those listed above with respect to the first
step and the like.
The third step can be effected by contacting
compound (B''') with the appropriate R''' halide having
the desired R' ' ' group, preferably in an inert organic
solvent. The third step is also typically conducted ln
situ with the reaction product mixture of the second step.
The third step of this process is typically
conducted at temperatures in the range of about from -30
to 30C, preferably 22 to 25C for about from 1 to 18
hours, preferably 1 to 5 hours using about from 1 to 10
moles, preferably 1 to 1.5 moles of R' ' 'X' per mole o~
B'''. Suitable inert organic solvents include those given
above with respect to the first step of this process, and
the like. The R' ' 'X' halides are generally known com-
pounds and can be prepared by known procedures or obvious
modifications thereof (e.g., substitution of appropriate
reactants and solvents).
The starting materials of Formula (B') can be
prepared by the following schematically represented
process:
X
~ CH2CN + RllOCCH2OR10 > (B')
(B) (C')
wherein Rll is lower alkyl (preferably methyl)
and R10, Y and X are as defined hereinabove.
This process can be conveniently effected by
~;~s~
01 -13-
contacting Compound (B) with Compound (C'), and a strong
base under reactive conditions, preferably in an inert
05 organic solvent.
Typically, this process is conducted using the
same conditions as described hereinabove with respect to
the preparation of Compound (A) save that reactant C' is
used in place of reactant C. The reactants of Formula C'
are simple alkyl alkoxyacetate esters, for example,~methyl
methoxyacetate. The preparation of such compounds is well
known to the art.
The compound of Formula (I) wherein one or both
of Rl and R2 are substituted can be pr~pared by alkylation
of the amino group of the corresponding compounds for
formula I'':
X X
~ ~ R2 z,. > ~ O
H\NJ~ Rl ,~
25(I ") (I''')
wherein R, Rl, X and Y are as defined here-
inabove; and R2 is as defined for R2 but is not
hydrogen; and R2 z~ is an alkylation agent having
the appropriate R2 or appropriate Rl group if
dialkylation is desired.
This process can be effected by contacting
Compound (I'') with a suitable alkylation agent capable of
alkylating primary or secondary amino groups.
For example, this can be effected by contacting
Compound (I'') with R2 iodide or bromide, preferably in an
inert organic solvent and preferably in the presence of a
scavenger base. Typically, this process is conducted at
temperatures in the range of about from 0 to 100C,
preferably 20 to 45C for about from 1.0 to 72.0,
01 -14-
preferably 2.0 to 18.0 hours. Where it i5 desired to
monoalkylate, then typically about from 1.0 to 1.1 moles
05 of R2 halide reactant is used per mole of Compound
(I''). Where it is desired to alkylate both amino
hydrogens, then typically about from 1.9 to ~.0 moles of
R2 halide are used per mole of Compound (I''). In the
case where it is desired to prepare the compound wherein
R2 is alkoxyalkyl or alkylthioalkyl, it is preferred to
use a large excess of R2 halide even where monoalkylation
is desired; for example 3 to 6 moles of R2 z~ per mole of
I''. Further alkylation can be effected in a second step
if desired. Also variation in Rl and R2 can be effected
by first alkylating only one of the two amino hydrogens
and then alkylating the second amino hydrogen with an
alkylating agent having a different R2 group. The
compounds wherein Rl and R2 together with the amino
nitrogen atoms form a saturated heterocycle can be
prepared by using the appropriate ~ (CH2)2_5-Z'',
wherein Z'' is Cl or Br alkylating agent. The RlR2N
unsaturated heterocycle can be prepared by using the
appropriate c1s-alkenyl dihalide, wherein one of the halo
atoms is on each of the terminal alkenyl carbon. ~uitable
inert organic so1vents which can be used, include, for
example, li~uid halogenated alkanes; for example,
methylene chloride, carbon tetrachloride, or dichloro-
ethane; also useful are tetrahydrofuran and the like.
Suitable scavenger bases which can be used include, for
example, the bases described hereinabove with respect to
the reaction of Compound (B) with Compound ~C).
The compounds of Formula (I "'~ wherein Rl is
lower alkyl (e.g. methyl) and R2 is hydrogen or lower
alkyl, are advantageously prepared using dialkyl sulfate
as the alkylating agent. This can be conveniently
effected by contacting the compound of Formula I wherein
one or both of Rl and/or R2 are hydrogen with the desired
lower alkyl sulEate in the presence of a strong base and
preferably in an inert organic solvent in the presence of
a phase transfer agent. Typically, this process is con-
~2~
01 -15-
ducted at temperatures in the range of about from 0 to
100C, preferably 20 to 45C, using about from 1.0 to
oS 4.0 moles of dialkyl sulfate per mole of Compound I. An
excess, typically about 2.5 mole of base is used. Prefer-
ably, this process is also conducted in an inert organic
solvent such as, for example, methylene chloride, carbon
tetrachloride, dichloroethane, tetrahydrofuran, and the
like.
Suitable strong bases which can be used include,
for example, sodium hydroxide, potassium hydroxide, sodium
ethoxide, sodium carbonate, potassium carbonate, and the
like. Suitable phase transfer agents are agents which
transfer hydrophilic ions into a lipophilic organic medium
and include, for example, benzyl triethylammonium
chloride, tetra-n-butylammonium chloride, methyltrioctyl-
ammonium chloride, and the like.
The compatible salts of Formula (I) can be
~o prepared by conventional procedures for example by
treating the compound of Formula (I) wherein Rl and/or R2
are hydrogen with a suitable strong base such as, for
example, n-butyllithium, sodium hydride, potassium
hydride, and the like, having the desired cation, by con-
~5 ventional procedures to yield the corresponding Rl and/orR2 cation salts. The enolate salts can be prepared by
treating the Rl and/or R2 cation salts with base via
conventional procedures. Additional variations in the
salt cation can also be effected via ion exchanye with an
ion exchange resin having the desired cation.
General Process Conditions
In the above-described processes, it is gener-
ally preferable to separate the respective products before
proceeding with the next step in the reaction sequence~
except where described as an in situ step or unless other-
wise expressly stated. These products can be recovered
from their respective reaction product mixtures by any
suitable separation and purification procedure, such as,
for example, recrystallization and chromatography.
Suitable separation and purification procedures are~ for
~ lZS2~
01 -16-
example, illustrated in the Examples set forth
hereinbelow.
05 Generally, the reactions described above are
conducted as liquid phase reaction and hence pressure is
generally not significant except as it affects temperature
(boiling point) where reactions are conducted at reflux.
Therefore, these reactions are generally conducted at
pressures of about from 300 to 3,000 mm of mercury and
conveniently are conducted at about atmospheric or ambient
- pressure.
It should also be appreciated that where typical
or preferred process conditions (e.g., reaction tempera-
tures, times, mole ratios of reactants, solvents, etc.)
have been given, that other process conditions could also
be used. Optimum reaction conditions (e.g., temperature,
reaction time, mol ratios, solvents, etc.) may vary with
the particular reagents or organic solvents used but can
be determined by routine optimization procedures.
Where optical isomer mixtures are obtained, the
respective optical isomers can be obtained by conventional
resolution procedures. Geometric isomers can be separated
by conventional separation procedures which depend upon
~S differences in physical properties between the geometric
lsomers .
Definitlons
As used herein the following terms have the
following meanings unless expressly stated to the
contrary:
The term "lower alkyl" refers to both straight-
and branched-chain alkyl groups having a total of from 1
through ~ carbon atoms and includes primary, secondary and
tertiary alkyl groups. Typical lower alkyls include, for
3S example, methyl, ethyl, n-propyl, isopropyl, n-butyl,
t-butyl.
The term "alkylene" refers to both straiyht
chained and branched chained alkylene groups and includes,
for example,
sz~
01 -17-
-CH2-; -CH2-CH2-, -CH~CH2- and the like.
05 The term "lower alkenyl" refers to alkenyl
groups having 2 through 6, preferably 2 through 4, carbon
atoms and includes, for example, vinyl, l-propenyl,
2-propenyl, 1-methylvinyl, l-butenyl, 2-methylprop-1-enyl
and the like.
The term "lower alkoxy" refers to the group -OR'
wherein R' is lower alkyl.
The term "lower alkylthiol' refers to the group
-SR' wherein R' is lower alkyl.
The term "lower alkoxyalkyl" refers to the group
R'OR''- wherein R' and R'' are independently straight
chain or branched chain alkyl groups haviny 1 through 3
carbon atoms~
The term "lower alkylthioalkyl" reEers to the
group R'SR"- wherein R' and R'' are independently
straight chain or branched chain alkyl groups having 1
through 3 carbon atoms.
The term "lower alkoxycarbonylalkyl" refers to
the group
O
R'OCR''-
wherein R' is lower alkyl and R'' is alkylene having 1
through 4 carbon atoms and can be straight or branched
chained. Typical alkoxycarbonylalkyl groups include for
example, -CH2C(O)OCH3; -CH(CH3)C(O)OC2H5, and the like.
The term "halo" refers to the group of fluoro,
chloro, bromo and iodo.
The term "lower haloalkyl" refers to haloalkyl
compounds ha~ing 1 through 4 carbon atoms and 1 through 3
halo atoms independently selected from the group of
fluoro, chloro, bromo and iodo. Preferably the lower
haloalkyl group has 1 or 2 carbon atoms.
The term "lower haloalkoxy" refers to "lower
~ ~Z~4~`~8
Ol -18- 61936-1612
alkoxy" groups having l throu(3h 3 halo atoms independently
selected from the group of fluoro, chloro, bromo or iodo.
oS The term "aryl" refers to aryl groups haviny 6
throuyh 10 carbon atoms and includes, for example, phenyl,
naphthyl, indenyl. Typically the aryl group will be
phenyl or naphthyl as compounds haviny such groups are
more readily available commercially than other aryl
; lO compounds.
The term "substituted aryl" refers to aryl
groups having 1 through 3 substituents independently
,~ : selected from the group of lower alkyl, lower alkoxy,
halonitro, or haloalkyl having 1 through 3 carbon atoms
lS and l through 3 halo atoms. Typical substituted aryl
groups include, for example, 2-fluorophenyl, 2-
chlorophenvl, 2,6-dimethylphenyl, 4-fluorophenyl,
2-methylphenyl, 2-chloro,3-chloromethylphenyl, 2-nitro,5-
methylphenyl, 2,6-dichlorophenyl, 3-trifluoromethylphenyl,
2-methoxyphenyl, 2-bromonaphth-1-yl, 3-methoxyinden-1-yl,
and the like.
The term "arylalkylene" refers to the group
ArR3- wherein Ar is aryl and R3 is alkylene having 1
through 3 carbon atoms and includes both straight-chained
and branched-chained alkylenes, for example, methylene,
ethyl, l-methylethyl, and pro~yl.
The term "(substituted aryl)alkylene" or
"ring-substituted arylalkylene" refers to the group Ar'R3-
wherein Ar' is substituted aryl and R3 is alkylene as
defined with respect to arylalkylene.
The term "saturated nitrogen heterocycle" as
used herein with respect to Rl and R~ of formula I refers
to the yroups having the formula:
~2c~ CH2
(CH2)n
wherein n is l, 2, or 3.
,~,.. .
01 -19- ~1936-1612
The term "unsaturated nitrogen heterocycle" as
used herein with respect to Rl and R2 of formula I refer
05 to the groups having the formulas:
I
N N N
~,~ L ~ ~
~ ~ ~ N~ ~
The term "compatible salts" refers to salts
which do not significantly alter the herbicidal properties
of the parent compound. Suitable salts include cation
salts such as, for example, the cation salts of lithium,
sodium, potassium, alkali earth metals, ammonia, quater-
nary ammoniu~ salts, and the like.
The term "room temperature" or "ambient
temperature" refers to about 20-25C.
Utility
The compounds of Formula (I) exhibit both
pre-emergence and post-emergence herbicidal activity and
exhibit especially good pre-emergence herbicidal activity.
Generally, for post-emergent applications, the
herbicidal compounds are applied directly to the foliage
or other plant parts. For pre-emergence applications, the
herbicidal compounds are applied to the growth medium, or
prospective growth medium, for the plant. The optimum
amount of the herbicidal compound or composition will vary
with the particular plant species, and the extent of plant
growth, if any, and the particular part of the plant which
is contacted and the extent of contact. The optimum
dosage can also vary with the general location, or
environment ~e.g., sheltered areas such as greenhouses
~ compared to exposed areas such as fields), and type and
degree of control desiredO Generally, Eor both pre- and
.~ ,.
~l -20-
post-emergent control, the present compounds are applied
at rates of about from 0.02 to 60 kg/ha, preferably about
OS from 0.02 to lO kg/ha.
Also, although in theory the compounds can be
applied undiluted, in actual practice they are generally
applied as a composition or formulation comprising an
effective amount of the compound(s) and an acceptable car-
rier. An acceptable or compatible carrier (agriculturallyacceptable carrier) is one which does not significantl~
adversely affect the desired biological effect achieved by
the active compounds, save to dilute it. Typically, the
composition contains about from 0.05 to 95~ by weight of
the compound of Formula (I) o mixtures thereof.
Concentrates can also be made having high concentrations
designed for dilution prior -to application. The carrier
can be a solid, liquid, or aerosol. The actual composi-
tions can take the form of granules, powders, dusts,
solutions, emulsions, slurries, aerosols, and the like.
Suitable solid carriers which can be used
include, for example, natural clays (such as kaolin, atta-
pulgite, montmorillonite, etc.), talcs, pyrophyllite,
diatomaceous silica, synthetic fine silica, calcium
aluminosilicate, tricalcium phosphate, and the like.
Also, organic materials, such as, for example, walnut
shell flour, cotton-seed hulls, wheat flour, wood flour,
wood bark flour, and the like can also be used as
carriers. Suitable liquid diluents which can be used
include, for example, water, organic solvents (e.g.,
hydrocarbons such as benzene, toluene, dimethylsulfoxide,
kerosene, diesel fuel, fuel oil, petroleum naphtha, etc.),
and the like. Suitable aerosol carriers which can b0 used
include conventional aerosol carriers such as halogenated
alkanes, etc.
The composition can also contain various
promoters and surface-active agents which enhance the rate
of transpo~t of the active compound into the plant tissue
such as, for example, organic solvents, wetting agents and
01 -21-
oils, and in the case of compositions designed for pre-
emergence application agents which reduce the leachability
of the compound or otherwise enhance soil stability.
The composition can also contain various
compatible adjuvants, stabilizers, conditioners, insecti-
cides, fungicides, and if desired, other herbicidally
active compounds.
1~ At reduced dosages the compounds of the present
invention also exhibit plant growth regulatiny activity
and can be used to alter the normal growth pattern of
green plants.
The compounds of Formula (I) can be applied as
plant growth regulators in pure form, but more pragmatic-
ally, as in the case of herbicidal application, are
applied in combination with a carrier. The same types of
carriers as set forth hereinabove with respect to the
herbicidal compositions can also be used. Depending on
the d~sired application, the plant growth regulating com-
position can also contain, or be applied in combination
with other compatible ingredients such as desiccants,
defoliants, surface-active agents, adjuvants, fungicides,
and insecticides. Typically, the plant growth regulating
composition will contain a to~al of about from 0.005 to
90 wt. % of the compound(s) of Formula (I) depending on
whether the composition is intended to be applied directly
or diluted first.
A further understanding of the invention can be
had in the following non-limiting Preparation and
Examples. h'herein, unless expressly stated to th0 con-
trary, all temperatures and temperature ranges refer to
the Centigrade system and the term "ambient" or "room
temperature" refers to about 20-25C. The term "percent"
or "~" refers to weight percent and the term "mole" or
"moles" refers to gram moles. The term "equivalent"
refers to a quantity of reagent equal in moles, to the
moles of the preceding or succeeding reactant racited in
that example in terms of finite moles or finite weight or
volume. Where given, proton~magnetic resonance spectrum
Z~8
01 -22-
(p.m.r. or n.m.r.) were determined at 60 m~z, signals are
assigned as singlets ts), broad singlets (bs), doublets
05 (d), double doublets (dd), triplets (t), double triplets
(dt), quartets (q), and multiplets (m); and cps refers to
cycles per second. Also where necessary examples are
repeated to provide additional starting material for sub-
sequent examples.
EXAMP~ES
Example 1
(3-Trifluoromethylphenyl)-benzylcarbonyl-acetonitrile
In this example, 4.91 g of metallic sodium was
added to ~10 ml of anhydrous ethanol at room temperature
and stirred until all of the sodium dissolved. A mixture
containing 18.75 g of (3-trifluoromethylphenyl) aceto-
nitrile and 21.73 g of ethyl phenylacetate was then added
dropwise and the resulting mixture was stirred at reflux
~or about 18 hours. The mixture was then poured into
300 ml water and extracted three times with ethyl ather.
The pH of the extracted agueous layer was adjusted to a pE~
of about 1 with aqueous 10 wt. ~ hydrochloric acid and
again extracted three times with ethyl ether. The organic
layer was washed twice with saturated aqueous sodium
bicarbonate, dried over magnesium sulfate and evaporated
to dryness under vacuum affording 22.6 g of the title
compound.
Similarly, by adapting the above procedure using
the appropriately substituted-phenyl acetonitrile and
ethyl-substituted phenyl acetate starting materials, the
following compounds can be prepared:
(5-chloro-3-trifluoromethylphenyl)-
benzylcarbonyl-acetonitrile;
(4-chloro-3-trifluoromethylphenyl)-
benzylcarbonyl-acetonitrile;
(2-bromo-3-trifluorcmethylphenyl)-benzyl-
! carbonyl-acetonitrile;
(6-fluoro-3-trifluoromethylphenyl)-benzyl
carbonyl-acetonitrile;
(4-methyl-3-trifluoromethylphenyl)-benzyl-
carbonyl-acetonitrile;
~S~8
: -23-
01
(5-methoxy-3-trifluoromethylphenyl)-benzyl-
carbonyl-acetonitrile;
(6-methyl-3-trifluoromethylphenyl)-benzyl-
05 carbonyl-acetonitrile;
(3,5-di-trifluoromethylphenyl)-benzylcarbonyl-
acetonltrile;
(3-difluoromethoxyphenyl)-benzylcarbonyl-
acetonitrile;
(3-trifluoromethoxyphenyl)-benzylc~rbonyl-
acetonitrile;
(3-trifluoromethylphenyl)-(4-fluorobenzyl-
carbonyl)-acetonitrile;
(3-trifluoromethylphenyl)-1-naphthylmethylene-
acetonitrile;
~ (2-chloro-3-methylphenyl)-benzylcarbonyl-
: acetonitrile;
~4-ethyl-3-methylphenyl)-benzylcarbonyl-
acetonitrile;
(5-methoxy-3-chlorophenyl)-benzylcarbonyl-
acetonitrile;
(3-iodophenyl)-benzylcarbonyl-acetonitrile;
(3-difluorornethylthiophenyl)-benzylcarbonyl-
acetonitrile;
(3-trifluoromethylthiophenyl)-benzylcarbonyl-
acetonitrile;
(3,5-diethoxyphenyl)-benzylcarbonyl-aceto-
nitrile;
(3-bromophenyl)-(2-nitrobenzylcarbonyl)-aceto-
nitrile;
(2-chloro-3-methylphenyl)-benzylcarbonyl-
acetonitrile;
(3-brorno-2-ethylphenyl)-naphth-1-ylmethylene-
carbonyl-acetonitrile;
(2,3-dimethylphenyl)-beta-naphth-1-ylmethyl-
carbonyl-acetonitrile;
(3-chlorophenyl)-benzylcarbonyl-acetonitrile;
(3-methylphenyl)-benzylcarbonyl-acetonitrile;
(3-t-butoxyphenyl)-benzylcarbonyl-acetonitrile;
01 -24-
(3-propylphenyl)-benzylcarbonyl-acetonitrile;
(3-bromophenyl)-benæylcarbonyl-acetonitrile;
05 (3-iodophenyl)-(3-nitrobenzylcarbonyl)-
acetonitrile;
(3-trifluoromethylphenyl)-(2,3-dichlorobenzyl-
carbonyl)-acetonitrile;
(3-methoxyphenyl)-1-naphthylmethylenecarbonyl-
acetonitrile;
(3-trifluoromethyl)-(3-chloro-8-fluoronaphth-1-
ylmethylenecarbonyl)-acetonitrile;
(3-trifluoromethyl)-[(2-trifluoromethyl-3-
methyl-8-methoxy-napth-1-yl)methylenecarbonyl]-aceto-
nitrile;
(3-trifluoromethyl)-(inden-1-ylmethylene-
carbonyl)-acetonitrile; and
(3-trifluoromethyl)-(2-fluoroinden-1-yl-
methylenecarbonyl)-acetonitrile.
Example 2
2-Phenyl-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2,3-dihydrofuran
In this example a solution containing 21.8 g of
(3-trifluoromethylphenyl)-benzylcarbonyl-acetonitrile,
dissolved in 60 ml of acetic acid was treated dropwise
with a solution of 12.65 g of bromine in 20 ml of glacial
acetic acid. The reaction mixture was stirred for about
16 hours at room temperature. The reaction mixture was
poured into 250 ml of water and the resulting mixture was
extracted three times with ethyl ether. The organic
extracts were washed with saturated aqueous sodium bicar-
bonate, dried over magnesium sulfate and concentrated
in vacuo to yield 8,4 g of white solid which was dried
affording 7.0 g of the title compound.
Similarly, by adapting the above procedure to
the compounds listed in Example 1, the following compounds
can be prepared:
2-phenyl-3-oxo-4-(5-chloro-3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
1;2S~
01 -25-
2-phenyl-3-oxo-4-(4-chloro-3-tr.ifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
OS 2-phenyl-3-oxo-4-(2-bromo-3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(6-fluoro-3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(4-methyl-3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(5-methoxy-3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(6-methyl-3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-~3,5-di-trifluoromethylphenyl)-
5-amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-difluoromethoxyphenyl)-5-
amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-trifluoromethoxyphenyl)-5-
~o amino-2,3-dihydrofuran;
2-(4-fluorophenyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-~1-naphthyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(2-chloro 3-methylphenyl)-5-
amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(4-ethyl-3-methylphenyl)-5-
amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(5-methoxy-3-chlorophenyl)-5-
amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-iodo2henyl)-5-amino-2,3-
dihydrofuran;
2-phenyl-3-oxo-4-(3-difluoromethylthiophenyl)-5
amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-trifluoromethylthiophenyl)-
5-amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3,5-diethoxyphenyl)-5-amino-
2,3-dihydrofuran;
2-(2-nitrophenyl)-3-oxo-4-~3-bromophenyl)-5-
amino-2,3-dihydrofuran;
01 -26-
2-phenyl-3-oxo-4-(2 chloro-3-methylphenyl)-5-
amino-2,3-dihydrofuran;
05 2~ naphthyl)-3-oxo-4-(3-bromo-2-ethylphenyl)-
5-amino-2,3-dihydrofuran;
2-(1-naphthyl)-3-oxo-4-(2,3-dimethylphenyl)-5-
amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-chlorophenyl)-5-amino-2,3-
dihydrofuran;
2-phenyl-3-oxo-4-(3-methylphenyl)-5-amino-2,3-
dihydrofuran;
2-phenyl-3-oxo-4-(3-butoxyphenyl)-5-amino-2,3-
dihydro~uran;
2-phenyl-3-oxo-4-(3-propylphenyl)-5-amino-2,3-
dihydrofuran;
2-phenyl-3-oxo-4-(3-bromophenyl)-5-amino-2,3-
dihydrofuran;
2-(3-nitrophenyl)-3-oxo-~-(3-iodophenyl)-5-
amino-2,3-dihydrofuran;
2-(2,3-dichlorophenyl)-3-oxo-4-(3-trifluoro-
methylphenyl)~5-amino-2,3-dihydrofuran;
2-(1-naphthyl)-3-oxo-4-(3-methoxyphenyl)-5-
amino-2,3-dihydrofuran;
2-(3-chloro-8-fluoronaphth-1-yl)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(2-trifluoromethyl-3-methyl-8-methoxy-naphth-
l-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2,3-
dihydroEuran;
2-inden-1-yl-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2,3-dihydrofuran; and
2-(2-fluoroinden-1-yl) 3-oxo-4-(3-trifluoro-
methylphenyl)-5-amino-2,3-dihydrofuran.
Example 3
2-Methyl-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2,3-dihydrofuran,
A dry, 500-ml, three-neck, round-bottom flask
equipped with a mechanical stirrer, addition funnel and a
reflux condenser was charged with 100 ml of ethanol. To
the stirred solvent were added 3.5 g of sodium. After all
lZ~Z~;8
01 -27-
the metal had dissolved, a solution of 13.0 g of ethyl
L-(+)-lactate and 18.5 g of m-trifluoromethylphenyl-
05 acetonitrile in 30 ml of ethanol was added dropwise to the
reaction mixture. The mixture became a deep red and after
the addition was complete, the mixture was heated at
reflux o~ernight (about 18 hours). The mixture was then
cooled to room temperature and added to 300 ml of water
and the resulting mixture was acidified (pH about 1) with
10% hydrochloric acid. The mixture was then extracted
with ether (three times) and the organic extracts were
washed (two times) with saturated aqueous sodium bicar-
bonate, dried over magnesium sulfate and concentrated
in vacuo to yield a thick oil. This oil was taken up in a
mixture of ether/petroleum ether and the desired compound
crystallized as a yellow powder. Two crops of crystals
were collected to afford a total of 4.7 y of the title
compound.
Similarly, by adapting the above procedure usin~
the corresponding appropriately substituted starting
materials the Eollowiny compounds can be prepared:
2-ethyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
amino-2,3-dihydrofuran;
2-ethyl-3-oxo-4-(5-chloro-3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-cyclopentyl-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2,3-dihydrofuran;
2-vinyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
amino-2,3-dihydrofuran;
2-allyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
amino-2,3-dihydrofuran;
2-allyl-3-oxo-4-(2-methoxy-3-triEluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-trifluoromethyl-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-difluoromethoxyphenyl)-5-
amino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-trifluoromethoxyphenyl)-5-
amino-2,3-dihydrofuran;
01 -2~-
2-(2-chlorovinyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
052-(2-chlorovinyl)-3-oxo-4-(5-propoxy-3-tri-
fluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(2-methoxy-3-chlorophenyl)-5-
amino-2,3-dihydrofuran;
2-ethyl-3-oxo-4-(2-chloro-3-fluorophenyl)-5-
10amino-2,3-dihydrofuran;
2-vinyl-3-oxo-4-(3-methyl-4-methoxyphenyl)-5-
amino-2,3-dihydrofuran;
2-allyl-3-oxo-4-(3,6-dimethylphenyl)-5 amino-
2,3-dihydrofuran;
lS2-trifluoromethyl-3-oxo-4-(3-trifluoromethyl-4-
bromophenyl)-5-amino-2,3-dihydrofuran;
2-(2-chlorovinyl)-3~oxo-4-(3-nitro-4-
methylphenyl)-5-amino 2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-methoxyphenyl)-5-amino 2,3-
20dihydrofuran;
2-methyl-3-oxo-4-(3-difluoromethylthiophenyl)-5-
amino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-trifluoromethylthiophenyl)-
5-amino-2,3-dihydrofuran;
252-ethyl-3-oxo-4-(3-chlorophenyl)-5-amino-2,3-
dihydrofuran;
2-vinyl-3-oxo-4-(3-methylphenyl)-5-amino-2,3-
dihydrofuran;
2-allyl-3-oxo-4-~3,5 di(trifluoromethyl)-
30phenyl]-5-amino-2,3-dihydrofuran;
2-trifluoromethyl-3-oxo-4-(4-fluorophenyl)-5-
amino-2,3-dihydrofuran;
2-(2-chlorovinyl)-3-oxo-4-(2-bromophenyl)-3-oxo-
5-amino-2,3-dihydrofuran;
352-propyl-3-oxo-4-(2-methoxy-3-chlorophenyl)-5-
amino-2,3-dihydrofuran;
2-butyl-3-oxo-4-(2-chloro-3-fluorophenyl)-5-
amino-2,3-dihydrofuran;
2-vinyl-3-oxo-4-(3-chloro-4-methoxyphenyl)-5-
40amino-2,3-dihydrofuran;
S~ ;B
-29- 61g36-1612
2-allyl-3~oxo-4-(3,5-dimethylphenyl)-5-amino-2,3-
dihydrofuran;
2-(trifluoromethyl)-3-oxo-4-(3-tri-fluoromethyl-5-
bromophenyl)-5-amino-2,3-dihydrofuran;
2-(2-chlorovinyl)-3-oxo-4-(3-fluoro-4-methyl-
phenyl)-3~oxo-5-amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-methoxyphenyl)-5-amino-2,3-di-
hydrofuran;
2-methyl-3-oxo-4-(3,5-difluorophenyl)-5-amino-2,3-
dihydrofuran;
2-vinyl-3-oxo-4-(3,5-diethylphenyl)-5-amino-2,3-
dihydrofuran;
2-allyl-3-oxo-4-(3-propoxyphenyl)-5-amino-2,3-di-
hydrofuran;
2-trifluoromethyl-3-oxo-4-(3-fluorophenyl)-5-amino-
2,3-dihydrofuran;
2-propyl-3~oxo-4-(3-bromophenyl)-3-oxo-5-amino-2,3-
dihydrofuran;
2-phenyl-3-oxo-4-(2-iodo-3-fluorophenyl)-5-amino-
2,3-dihydrofuran;
2-benzyl-3-oxo-4-(2-isopropoxy-3-trifluoro-methyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-(3-chlorophenyl)-3-oxo-4-(2,3-dimethylphenyl)-
5-amino-2,3-dihydrofuran;
2-naphth-1-yl-3-oxo-4-(3-trifluoromethyl-4-bromo-
phenyl)-5-amino-2,3-dihydrofuran;
2-(3-methylphenyl)-3-oxo-4-(3-butyl-4-methylphenyl)-
3-oxo-5-amino-2,3-dihydrofuran;
2-(3-fluorophenyl)-3-oxo-4-(3-chlorophenyl)-5-amino-
2,3-dihydrofuran;
SZ ~i8
- 29a - 61936-1612
2-(2,3,5-trifluorophenyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-(3-methylnapth-1-yl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-(1-chlorovinyl)-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2,3-dihydrofuran;
2-fluoromethyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
amino-2,3-dihydrofuran;
~ ` lZS~4~3
-30- 61936-1612
2-methoxymethylene-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2,3-dihydrofuran;
2-propoxymethylene-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2,3-dihydrofuran;
2-ethoxymethylene-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2,3-dihydrofuran;
2-(2-methoxypropyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-methylthiomethylene-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran; and
2-(1-propylthioethyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran.
Example 4
(3-Trifluoromethylphenyl)-
methoxyacetyl-acetonitrile_
In this example 5.6 grams of metallic sodium was
added to 120 ml of anhydrous ethanol at room temperature under
a nitrogen atmosphere resulting in the evolution of hydroyen.
After evolution of hydrogen was completed a mixture containing
20 30 g of (3-trifluoromethylphenyl)-acetonitrile and 18.5 g of
methyl methoxyacetate in anhydrous ethanol was added and the
resulting mixture refluxed for 3 to 4 hours. The mixture was
then added to 300 ml of water and extracted three times with
petroleum ether. The remaining aqueous phase was acidified
with aqueous 10~ hydrochloric acid to about pH 1 and extracted
three times with ethyl ether. The ethyl ether extracts were
combined, washed twice with saturated aqueous sodium bi-
carbonate, dried over magnesium sulfate and concentrated by
evaporation. The concentrate was evaporated under high vacuum
affording an oil which was triturated with ethyl ether. This
mixture was -then filtered to remove solids and the filtrate
~!
s~
- 30a - 61936~1612
evaporated under vacuum affording 36.9 g of the title compound
as a brown solid.
Similarly, by adapting the above procedure but using
other (substituted and disubstituted phenyl) acetonitriles in
place of ~3-trifluoromethylphenyl)acetonitrile
~SZ~
01 -31-
the corresponding substituted and disubstituted phenyl
analogs of the title compound can be prepared.
05 Example 5
(3-Trifluoromethylphenyl)-
2-methoxvisovaleryl-acetonitrile
In this example 10 g o t3-trifluoromethyl-
phenyl)-methoxyacetyl-acetonitrile was added dropwise to a
slurry of 1.8~ g of sodium hydride in 20 ml of tetra-
hydrofuran at about 0C under a nitroyen atmosphere,
resulting in the evolution of hydrogen. After no further
evolution of hydroyen was observed, the mixture was cooled
to about -78C and 24.3 ml of 1.6M n-butyllithium in
hexane was added dropwise. The mixture was stirred for
1-1/2 hours at -78C and then stirred at about 0-4C for
twenty minutes. After this 3.9 ml (about 6.6~ g) of 2-
iodopropane was added dropwise and the mixture stirred
overnight (about 14-16 hours). The mixture was then added
to water, acidified with aqueous 10% hydrochloric acid and
extracted three times with ethyl ether. The ~xtracts were
combined, dried over magnesium sulfate and concentrated
under vacuum affording 11.4 g of the title compound as an
oil.
Similarly, by adapting the same procedure but
using the appropriate alkyl, aryl or substituted aryl,
iodide, bromide, or chloride in place of iodopropane the
following compounds can be prepared:
(3-trifluoromethylphenyl)-(2~methoxy-3-
phenylpropionyl)acetonitrile7
(3-trifluoromethylphenyl)-~2-methoxy-3-(2-
fluorophenyl)propionyl]acetonitrile;
(3-trifluoromethylphenyl)~[2-methoxy-3-(3-
methylphenyl)propionyl]acetonitrile;
(3-trifluoromethylphenyl)-[2-methoxy-3-(2-
ethoxyphenyl)propionyllacetonltrile;
(3-trifluoromethylphenyl)-[2-methoxy-3-(3-
nitrophenyl)propionyl]acetonitrile;
(3-trifluoromethylphenyl)-[2-methoxy-3-(2-
trifluoromethylphenyl)propionyl]acetonitrile;
~zs;~
01 -32-
(3-trifluoromethylphenyl)-[2-methoxy-3-(2-
chloro-3-propylphenyl)propionyl]acetonitrile;
05 (3-trifluoromethylphenyl)-[2-methoxy-3-(2-nitro-
3-methoxyphenyl)propionyl]acetonitrile;
(3-trifluoromethylphenyl)-[2-methoxy-3-(2-
fluoro-3-2',2'-dichloroethylphenyl)propionyl]acetonitrile;
(3-trifluoromethylphenyl)-[2-methoxy-3-(2,3-
dichloro-6-methylphenyl)propionyl]acetonitrile;
(3-trifluoromethylphenyl)-(2-methoxy-4-
phenylbutyryl)acetonitrile;
(3-trifluoromethylphenyl)-[2-methoxy-5-(2-
bromophenyl)valeryl]acetonitrile;
(3-trifluoromethylphenyl)-(2-methoxy-3-methyl-4-
phenylbutyryl)acetonitrile;
(3-trifluoromethyl)~(2-methoxy-3-naphth-1-
ylpropionyl)acetonitrile;
(3-trifluoromethyl)-[2-methoxy-3-(2-
fluoronaphth-l-yl)propionyl]acetonitrile;
(3-trifluoromethyl)-[2-methoxy-3-~3-butylnaphth-
l-yl)propionyl]acetonitrile;
(3-trifluoromethyl)-[2-methoxy-3-(5-
methoxynaphth-l-yl)propionyl]acetonitrile;
(3-trifluoromethyl)-[2-methoxy-3-(6-nitronaphth-
l-yl)propionyl]acetonitrile;
(3-trifluoromethyl)-[2-methoxy-3-(7-trifluoro-
methylnaphth-l-yl)propionyl]acetonitrile;
(3-trifluoromethyl)-[2-methoxy-3-(2-chloro-8-
methylnaphth-l-yl)propionyl]acetonitrile;
(3-trifluoromethyl)-[2-methoxy-3-(3-methoxy-5-
nitro-7-fluoromethylnaphth-1-yl)propionyl]acetonitrile;
(3-trifluoromethyl)-(2-methoxy-4-naphth-1-
ylbutyryl)acetonitrile;
(3-trifluoromethyl)-[2-methoxy-5-(8-
fluoronaphth-l-yl)valeryl]acetonitrile;
(3-trifluoromethyl)-[2-methoxy-3-methyl-3-~7-
methoxynaphth-l-yl)propionyl]acetonitrile;
(3-trifluoromethylphenyl)-(2-methoxy-3-inden-1-
ylpropionyl)acetonitrile; and
4~
-33- 61936-1612
(3-trifluoromethylphenyl)-[2-methoxy-3-~2-fluoro-
inden-l-yl)propionyl]acetonitrile.
Similarly, by adapting the above procedure using
other (mono or disubstituted phenyl)-(methoxyacetyl)ace-to-
nitriles in place of (3-trifluoromethylphenyl)-(2-methoxy-
acetyl)acetonitrile the corresponding mono or disubstituted
phenyl derivatives of the above compounds can be prepared.
Example 6
2-Isopropyl-3-oxo-4-
(3-trifluoromethylphenyl)-5-amino-2,3-dihydrofuran
In this example, a mixture containing 11.4 g of (3-
trifluoromethylphenyl)-(2-methoxyisovaleryl)acetonitrile and
7.8 g of concentrated sulfuric acid in 50 ml of acetic acid was
warmed to reflux for 30 minutes and -then concentrated by
evaporation under vacuum. The concentrate was mixed with di-
ethylether, washed three times with lN aqueous sodium
hydroxide, dried over magnesium sulfate and concentrated by
evaporation affording an oil. The oil was triturated in 20%
(vol.) ethyl acetate:80% petroleum ether and allowed to stand
overnight (14-16 hours). The solids were collected by filtra-
tion and washed three times with 20% (vol.) ethyl acetate:80%
petroleum ethyl affording 2.9 g of the title compound.
Similarly, by adapting the above procedure using
3-trifluromethylphenyl-dimethoxyacetyl-acetonitrile, which can
be prepared via the procedure of Example 1, and the other
compound products indicated in Example 5 -the following
compounds can be prepared:
2-methoxy-5-oxo-4-(3-trifluoromethylphenyl~-5-amino-
2,3-dihydrofuran-2-benzyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
amino-2,3-dihydrofuran;
2-(2-fluorobenzyl)-3-oxo-4-(3-trifluoromethyl-
- 33a - 61936-1612
phenyl)-5-amino-2,3-dihydrofuran;
2-(3-methylbenzyl)-3-oxo-4-(3-trifluoromethyl-
: phenyl)-5-amino-2,3-dihydrofuran;
2-(2-ethoxybenzyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran,
2-(3-nitrobenzyl)-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2,3-dihydrofuran;
`` ~Z~ ;8
01 ~34~
2-(4-fluorobenzyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
05 2-(2-trifluoromethylbenzyl)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(2-chloro-3-propylphenyl)-3-oxo-4-(3-tri-
fluoromethylphenyl)-S-amino-2,3-dihydrofuran;
2-(2-nitro-3-methoxyphenyl)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(2-fluoro-3-2 7 ~ 2'-dichloroethylbenzyl)-3-oxo-
4-(3-trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(2,3-dichloro-6-methylbenzyl)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(beta-phenethyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-[3-(2-bromophenyl)propyl]-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-[1-methyl-2-(phenyl)ethyl]-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-naphth-1-ylmethylene-3-oxo-4-(3-trifluoro-
methylphenyl)-5-amino-2r3-dihydrofuran;
2-(2-fluoronaphth-1-ylmethylene)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(3-butylnaphth-1-ylmethylene)-3-oxo-4-(3-tri- .
fluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(5-methoxynaphth-1-ylmsthylene)-3-oxo-4-(3-
trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(6-nitronaphth-1-ylmethylene)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(7-trifluorometnylnaphth-1-ylmethylene)-3-oxo-
4-(3-trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(2-chloro-8-methylnaphth-1-ylmethylene)-3-oxo-
4-(3-trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(3-methoxy-5-nitro~7-fluoromethylnaphth-1-yl)-
3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2,3-dihydro-
furan;
2-(beta-naphth-1-ylethyl)-3-oxo-4-(3-trifluoro-
methylphenyl)-5-amino-2,3-dihydrofuran;
-`~ 12~
01 -35-
2-[beta-(8-fluoronaphth-1-yl)ethyl]-3-oxo-4-(3-
trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
05 2-[1-(7-methoxynaphth-1-yl)ethyl]-3-oxo-4-(3-
trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-inden-1-ylmethylene-3-oxo-4-(3-trifluoro-
methylphenyl)-5-amino-2,3-dihydrofuran; and
2-(2-fluoroinden-1-ylmethylene)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-amino-2,3-dihydrofuran.
Similarly, by adapting the above procedure using
the corresponding mono- and disubstituted analogs of the
starting material for the above compounds the corre-
sponding 4-(3-methylphenyl); 4-(3-beta-fluoroethoxy-
phenyl); 4-(3-diEluoromethylenethiophenyl~; 4-(3-
chlorophenyl); 4-(2-bromo-3-trifluoromethylphenyl)- and 4-
(2-methyl-3-difluoromethylenethiophenyl analogs of the
above compounds can be preparedO
Example 7
2-Phenyl-3 oxo-4-(-3-trifluoromethylphenyl)-
5-methylamino-2,3-dihydrofuran
In this example about 1 g of solid sodium
hydroxide in 4.0 ml of water was added to a mixture of 3 9
of 2 phenyl-3-oxo-4-(3-trirluoromethylphenyl)-5-amino-2,3-
dihydrofuran in 50 ml of methylene chloride at room
temperature followed by the addition of 1.19 9 of dimethyl
sulfate and 0.21 g oE benzyltriethyl ammonium chloride.
The resulting two-phase mixture was stirred at room tem-
perature for about two hours and then washed three times
with water, dried over magnesium sulfate and then concen-
trated by evaporatiGn under vacuum~ The residue was then
purified by chromatography over silica gel eluting with
mixtures of tetrahydrofuran and chloroform affording the
title compound.
Similarly, by adapting the above procedure using
the products listed in Examples 2, 3 and 6 as starting
materials, the corresponding 5-methylamino homologs
thereof can be prepared, for example:
2-phenyl 3-oxo-4-l5-chloro-3-trifluoromethyl-
phenyl)-5-methylamino-2,3~dihydrofuran;
5Z~i8
01 -36-
2-phenyl-3-oxo-4-(4-chloro-3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
05 2-phenyl-3-oxo-4-(2-bromo-3-trifluoromethyl-
phenyl)-5~methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(6-fluoro-3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(4-methyl-3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(5-methoxy-3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(6-methyl-3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3,5-di-trifluoromethylphenyl)-
5-methylamino-2,3-dihydrofuran;
: 2-phenyl-3-oxo-4-(3-difluoromethoxyphenyl)-5-
; methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-trifluoromethoxyphenyl)-5-
methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-trifluoromethylthiophenyl)-
S-methylamino-2,3-dihydrofuran;
2-(4-fluorophenyl) 3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-(1-naphthyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(2-chloro-3-methylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(4-ethyl-3-methylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(5-methoxy-3-chlorophenyl)-5-
methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-iodophenyl)-5-methylamino-
2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-difluoromethylthiophenyl)-5-
methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-trifluoromethylthiophenyl)-
5-methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3l5-diethoxyphenyl)-5-
methylamino-2,3-dihydrofuran;
- 3LZ~ 8
01 ~37~
2-(2-nitrophenyl)-3-oxo-4-(3-bromophenyl)-5-
methylamino-2,3-dihydrofuran;
05 2-phenyl-3-oxo-4-(2-chloro-3-methylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-(1-naphthyl)-3-oxo-4-(3-bromo-2-ethylphenyl)-
5-methylamino-2,3-dihydrofuran,
2-(1-naphthyl)-3-oxo-4-(2,3-dimethylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-chlorophenyl)-5-methylamino-
2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-methylphenyl)-5-methylamino-
2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-butoxyphenyl)-5-methylamino-
2,3-dihydrofuran;
2-phenyl-3-oxo-4-(2-propylphenyl)-5-methylamino-
2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-bromophenyl)-5-methylamino-
2,3-dihy~rofuran;
2-~3-nitrophenyl)-3-oxo-4-(3-iodophenyl)-5-
methylamino-2,3-dihydrofuran;
2-(2,3-dichlorobenzyl)-3-oxo-4-(2-trifluoro-
methylphenyl)-5-methylamino-2,3-dihydrofuran~
2-(1-naphthyl)-3~oxo 4-(3-methoxyphenyl)-5-
methylamino-2,3-dihydrofuran;
2-(3-chloro-8-fluoronaphth-1-yl) 3-oxo-4-(3-
trifluoromethylphenyl)-S-methylamino-2,3-dihydrofuran;
2-(2-trifluoromethyl-3-methyl-8-methoxynaphth-1-
yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-methylamino-2,3-
dihydrofur,ln;
2-inden-1-yl-3-oxo-4-(3-trifluoromethylphenyl)-
5-methylamino-2,3-dihydrofuran;
2-(2-fluoroinden-1-yl)-3-oxo-4-(3-trifluoro-
methylphenyl)-5-methylamino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-ethyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
methylamino-2,3-dihydrofuran;
S~;B
01 -38-
2-ethyl-3-oxo-4-(5-chloro-3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
05 2-cyclopentyl-3-oxo-4-(3-trifluorome~hylphenyl)-
5-methylamino-2,3-dihydrofuran;
2-vinyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-allyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-allyl-3-oxo-4-(2-methoxy-3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-trifluoromethyl-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-difluoromethoxyphenyl)-5-
methylamino-2,3-dihydrofuran
2-methyl-3-oxo-4-(3-trifluoromethoxyphenyl)-5-
methylamino-2,3-dihydrofuran;
2-(2-chlorovinyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-(2-chlorovinyl)-3-oxo-4-(5-nitro-3-tri~luoro-
methylphenyl)-5-methylamino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(2-methoxy-3-chlorophenyl)-5-
methylamino-2,3-dihydrofuran;
2-ethyl-3-oxo-4-(2-chloro-3-fluorophenyl)-5-
methylamino-2,3-dihydrofuran;
2-vinyl-3-oxo-4-(3-methyl-4-methoxyphenyl)-5-
methylamino-2,3-dihydrofuran;
2-allyl-3~oxo-4-(3,6-dimethylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-trifluoromethyl-3-oxo-4-(3-trifluoromethyl-4-
bromophenyl)-5-methylamino-2,3-dihydrofuran;
2-(2-chloro~inyl)-3-oxo-4-(3-nitro-4-methyl-
phenyl)-3-oxo-5-methylamino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-methoxyphenyl)-5-methyl-
amino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-difluoromethylthiophenyl)-5-
methylamino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-trifluoromethylthiophenyl)-
5-methylamino-2,3, dihydrofuran;
~S~
01 -39~
2-ethyl-3-oxo-4-(3-chlorophenyl)-5-methylamino-
2,3-dihydrofuran;
05 2-vinyl-3-oxo-4-(3-methylphenyl~-5-methylamino-
2,3-dihydrofuran;
2-allyl-3-oxo-4-[3,5-di(trifluoro~.ethyl)phenyl]-
5-methylamino-2,3-dihydrofuran;
2-trifluoromethyl-3-oxo-4-(4-fluorophenyl)-5-
methylamino-2,3-dihydrofuran;
2-(2-chlorovinyl)-3-oxo-4-(2-bromophenyl)-3-oxo-
5-methylamino~2,3-dihydrofuran;
2-propyl-3-oxo-4-(2-methoxy-3-chlorophenyl)-5-
methylamino-2,3-dihydrofuran;
2-butyl-3-oxo-4-(2-chloro-3-fluorophenyl)-5-
methylamino-2,3-dihydrofuran;
2-vinyl-3-oxo-4-(3-chloro-4-methoxyphenyl)-5-
methylamino-2,3-dihydro~uran;
2-allyl-3-oxo-4-(3,6-dimethylphenyl)-5-
methylamino-2,3-dihydrofuran
2-trifluoromethyl-3-oxo-4-(3-trifluoromethyl-5-
bromophenyl)-5-methylamino-2,3-dihydrofuran;
2-(2-chlorovinyl)-3-oxo-4-(3-fluoro-4-methyl-
phenyl)-3-oxo-5-methylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-methoxyphenyl)-5-methyl-
amino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3,5-difluorophenyl)-5-
methylamino-2,3-dihydrofuran;
2-vinyl-3-oxo-4-(3,5-diethylphenyl)-5-methyl-
amino-2,3-dihydrofuran;
2-allyl-3-oxo-4-(3-propoxyphenyl)-S-msthylamino-
2,3-dihydrofuran;
2-tri~luoromethyl-3-oxo-4-(3-fluorophenyl)-5-
m~thylamino-2,3-dihydrofuran;
2 propyl-3-oxo-4-(2-bromophenyl)-3-oxo-5-methyl-
amino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(2-iodo-3-fluorophenyl)-5-
methylamino-2~3-dihydrofuran;
2-benzyl-3-oxo-4-(2-isopropoxy-3-trifluoro-
methylphenyl) 5-methylamino-2,3-dihydrofuran;
-~0- 6193~-1612
r
2-(3-chlorophenyl)-3-oxo-4-(2,3-dimethylphenyl)-
5-methylamino-2,3-dihydrofuran;
2-naphth-1-yl-3-oxo-4-(3-trifluoromethyl-4-bromo-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-(3-methylphenyl)-3-oxo-4-(3-butyl-4-methylphenyl)-
3~oxo-5-methylamino-2,3-dihydrofuran;
2-(3-fluorophenyl)-3-oxo-4-(3-chlorophenyl)-5-
methylamino-2,3-dihydrofuran;
2-(2,3,5-trifluorophenyl)-3-oxo-4-(3-trifluoro-
methylphenyl)-5-methylamino-2,3-dihydrofuran; and
2-(3-methylnaphth-1-yl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-(l-chlorovinyl)-3-oxo-4-(3-trifluoromethylphenyl)-5
-methylamino-2,3-dihydrofuran;
2-fluoromethyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-methoxymethylene-3-oxo-4-(3-trifluoromethylphenyl)-
5-methylamino-2,3-di.hy-lrofuran;
2-propoxymethylene-3-oxo-4-(3-trifluoromethylphenyl)-
5-methylamino-2,3-dihydrofuran;
2-ethoxymethylene-3-oxo-4-(3-trifluoromethylphenyl)-
5-methylamino-2,3-dihydrofuran;
2-(2-methoxypropyl)-3-oxo-4-(3-trifluorome-thyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-methylthiomethylene-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran; and
2-(1-propylthioethyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran.
2-benzyl-3-oxo-4-(3-trifluoromethylphenyl)-5-methyl-
amino-2,3-dihydrofuran;
- 40a - 61936-1612
2-(2-fluorobenzyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran,
2-(3-methylbenzyl)-3-oxo-4-(3-trifluoromethyl-
phenyl~-5-methylamino-2,3-dihydrofuran;
2-(2-ethoxybenzyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-(3-nitrobenzyl)-3-oxo-4-(3-trifluoromethylphenyl)-
5-methylamino-2,3-dihydrofuran;
1~S~ 8
01 -41-
2-(4-fluorobenzyl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
OS 2-(2-trifluoromethylbenzyl)-3-oxo-4-(3-tri-
fluoromethylphenyl1-5-methylamino-2,3-dihydrofuran;
2-(chloro-3-propylphenyl)-3-oxo-4-(3-trifluoro-
methylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(2-nitro-3-methoxyphenyl)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(2-fluoro-3-2',2'-dichloroethylbenzyl)-3-oxo-
4-(3-trifluoromethylphenyl)-5-methylamino-2,3-
dihydrofuran;
2-(2l3-dichloro-6-methylbenzyl)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(beta-phenethyl)-3-oxo-4-(3-trifluoromethyl-
phenyl~-5-methylamino-2,3-dihydrofuran;
2- E 3-~2-bromophenyl)propyl]-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
~0 2-[1-methyl 2-(phenyl)ethyll-3-oxo-~-~3-tri-
fluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-naphth-1-ylmethylene-3-oxo-4-(3-trifluoro-
methylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(2-fluoronaphth-1-ylmethylene)-3-oxo-4~(3-tri-
fluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(3-butylnaphth-1-ylmethylene)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(5-methoxynaphth-1-ylmethylane)-3-oxo-4-(3-
trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2 (6-nitronaphth-1-ylmethylene)-3-oxo-4-(3-tri-
fluoromethylphenyl)-5-methylaminc-2,3-dihydrofuran;
2-(7-trifluoromethylnaphth-1-ylmethylene)-3-oxo-
4-(3-trifluoromethylphenyl)-5 methylamino-2,3-
dihydrofuran;
2-(2-chloro-8-methylnaphth-l-ylmethylene)-3
4-(3-trifluoromethylphenyl)-5-methylamino-2,3
dihydrcfuran;
2-(3-methoxy-5-nitro-7-fluoromethylr.aphth-1-yl)-
3-oxo-4-(3-trifluoromethylphenyl)-5-methylamino-2,3-
dihydrofuran;
- ~2 - ~ 61936-161~
"
0l 2-methoxy-3-oxo-4-(3-trifluoromethylphenyl)-
5-methylamino-2,3-dih~drofuran;
2-(beta-nauhth-l-ylethyl)-3-oxo-4-(3-triEluoro-
methylphenyl)-5-methylamino-2,3-dihydrofuran;
05 2-[beta-(8-fluoronaphth-l-yl)ethyl]-3-oxo-4-t3-
trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-[l-(7-methoxynaphth-l-yl)ethyl]-3-oxo-4-~3-
trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-inden-l-ylmethylene-3-oxo-~ -trifluoro-
methylphenyl)-5-methylamino-2,3-dihydrofuran; and
2-(2-fluoroinden-l-ylmethylene)-3-oxo-4-(3-tri
fluoromethylphenyl~-5-methylamino-2,3-dihydrofuran.
Similarly, by approximately doubliny the amount
of dimethylsulfate and increasiny the reaction time, the
corresponding 5-dimethylamino homoloys oE the above
compounds can be prepared. Similarly, by using
diethylsulfate in place of dimethylsulphate the
corresponding 5-ethylamino and 5-diethylamino homologs of
the above compounds can be prepared.
Exam~le 8
2-~2-Fluorophenyl)-3-oxo-4-(3-triEluoro-
methylp3henyl)-5-allylamino-2~3-dihydrofuran
One gram o~ sodium hydroxide in 9.0 ml oE water
was added to a mixture of 4.0 g of 2-(2-fluorophen~ 3-
oxo-~-~3-trifluoromethylphenyl) 5-amino-2,3-dihydrouran
in 80 ml of methylene chloride at room temperature
oll~wed by the addition of l.'t'~ y oE allyl bromide and
0.~7 g o benzyltriethylammoniull chloride. Th~ re5ultincJ
two-phase mixture was stirred at room temperature Eor
about 18 hours after which time it was washed three times
with water, dried Gver maynesium sulfate and concentrated
in vacuo. The residue was purifie~ by chromatography over
silica gel eluting with chloroform to yield 2.5 g of the
title compound.
Similarly, by applying this procedure to the
products listed in Examples 2, 3 and 6, the correspQndiny
5-allylamino analogs thereof can be prepared. Similarly,
by approximately doubliny the amount of allyl bromide and
sodium hydroxide, the correspondiny 5-diallylamino analoys
thereoE can be prepared.
. _~
3~
i~J
1~2~
01 ~43~
In a like manner, by using ethyl bromide in
place of allyl bromide, the corresponding 5-ethylamino and
~5 5-diethylamino analogs can be prepared.
Similarly, by following the same procedure by
respectively using methoxymethyl bromide, ethylthiomethyl
bromide, methyl bromoacetate, methyl 2-bromobutyrate, 1,5-
dibromopentane, and cis-1,4-dibromobut-1,3-diene in place
- lG of alkyl bromide the corresponding 5-methoxymethylamino,
5-ethylthiomethylamino, 5~methoxycarbonylmethylamino, 5-
'l-methoxycarbonylpropylamino), 5-piperidin-1-yl and 5-
pyrrol-l-yl analo~s of the products listed in Examples 2,
3 and 6 can be prepared for example:
2-phenyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
msthoxymethylamino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
methoxymethylamino-2,3-dihydrofuran;
2-ethyl-3-oxo-4-(3-tri1uoromethylphenyl)-5-
methoxymethylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
ethylthiomethylamino-2,3-dihydrofuran;
2-methoxy-3--oxo-4-(3-trifluoromethylphenyl)-5-
ethylthiomethylamino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
et.hylthiomethylamino-2,3-dihydrofuran;
2-ethoxymethylene-3-oxo-~-(3-trifluoromethyl-
phenyl)-5-ethylthiomethylamino-2,3-dihydrofuran;
2-ethyl-3-oxo-4-(3-trifluoromethylphenyl)~5-
ethylthiomethylamino-2,3-dihydrofuran;
2-phenyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
methoxycarbonylmethylamino-2,3-dihydrofuran;
2-methyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
methoxycarbonylmethylamino-2,3-dihydrofuran;
2-methylthiomethylene-3-oxo-4-(3-trifluoro~
methylphenyl)-5-methoxycarbonylmethylamino-2,3-
dihydrofuran;
2-ethyl-3-oxo-4-(3-trifluoromethylphenyl)-S-
methoxycarbonylmethylamino-2,3-dihydrofuran;
~2S~
01 ~44~
2-phenyl 3-oxo-4-~3-trifluoromethylphenyl~-5-(l-
methoxycarbonylprop-l-yl)amino-2,3 dihydrofuran;
05 2-methyl-3-oxo-4-(3-trifluoromethylphenyl)-5-(1-
methoxycarbonylprop-l-yl)amino-2,3 dihydrofuran;
2-fluoro-3-oxo-4-(3-trifluoromethylphenyl)-5-(1-
methoxycarbonylprop-l-yl)amino-2,3-dihydrofuran;
2-ethyl-3-oxo-4-(3-trifluoromethylphenyl)-5-(1-
methoxycarbonylprop-1-yl)amino-2,3-dihydrofuran;
2-naphth-l-yl-3-oxo-4-(3-trifluoromethylphenyl)-
5~ methox~carbonylprop-1-yl)amino-2,3-dihydrofuran;
2-inden-1-yl-3-oxo-4-(3-trifluoromethylphenyl)-
5-(l-methoxycarbonylprop-1-yl)amino-2,3-dihydrofuran,
2-phenyl-3-oxo-4--(3-trifluoromethylphenyl)-5-
piperidin-l-yl-2,3-dihydrofuran; and
2-phenyl-3-oxo-4-(3-trifluoromethylphenyl)-5-
pyr~ol-l-yl-2,3-dihydrofuran, etc.
Similarly, by applying the above procedures
using the 5-methylamino products of Example 7 as starting
materials, the corresponding 5-(~-methyl-N-allylamino), 5-
(N-methyl-N-ethylamino), 5-(N-methyl-N-methoxymethyl-
amino), 5-(N-methyl-N-ethylthiomethylamino), 5-(N-methyl-
N-methoxycarbonylmethylamino), and 5-(N-methyl-N-l'-me-
thoxycarbonylpropylamino) analogs can be prepared.
Example 9
Lithium salt of 2-phenyl-3-oxo-
4-(3-trifluoromethylphenyl)-5-methylamino-
2,3-dihydrofuran (R =-CH3, R2--Li)
In this example, 5.4 ml of 1.6M n-butyllithium
in hexane was added dropwise to a stirred solution
containing 2~36 g of 2-phenyl-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran in 25 ml of tetrahydro-
furan at -30C. The resulting mixture was stirred for
20 minutes and then concentrated in vacuo affording 2.8 g
of the title compound as a light brown solid. Elemental
analysis: calculated, C-63.74, H-3.84, N-4.13; found,
C-61.82, H-4.90, ~-3.48.
~L~2S;~;8
01 ~45~
Similarly, by adapting the above procedure, the
- corresponding lithium salts of the compounds of
05 Examples 2-5 can also be prepared.
Example 10
The compounds listed in Table A hereinbelow were
prepared using the appropriate starting materials and the
appropriate procedures described in the Examples
hereinabove.
12S;~4~ !3
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01 ~54~
il
Example ~ ~A~p~ ID
~ In this example, the compounds of ~b~e-~ were
`~ 05 respectively tested using the procedures described herein-
below for pre-emergent and post-emergent activity against
a variety of grasses and broad-leaf plants including one
grain crop and one broad-leaf crop. The compounds tested
are identified by compound number in ~ ~ hereinabove.
Pre-Emergent Herbicide Test
Pre-emergence herbicidal activity was determined
in the following manner.
Test solutions of the respective compounds were
prepared as follows:
355.5 m9 of test compound was dissolved in 15 ml
of acetone. 2 ml of acetone containing llO mg of a non-
ionic surfactant was added to the solution. 12 ml of this
stock solution was then added to 47.7 ml of water which
contained the same nonionic surfactant at a concentration
of 625 mg/l.
Seeds of the test vegetation were planted in a
pot of soil and the test solution was sprayed uniformly
onto the soil surface either at a dose of
27.5 micrograms/cm2 or in some instances as indicated in
Table 1 hereinbelow, certain of the compounds were tested
at a lower dosage of l5.6 micrograms/cm2. The pot was
watered and placed in a greenhouse. The pot was watered
intermittently and observed for seedling emergence, health
of emerging seedlings, etcO, for a 3-week period. At the
end of this period, the herbicidal effectiveness of the
compound was rated based on the physiological obser-
vations. A 0-to-lO0 scale was used, 0 representing no
phytotoxicity, lO0 representing complete kill. The
results of these tests are summarized in Table 1.
Post-Emergent Herbicidal_Test
The test compound was formulated in the same
manner as described above ~or the pre-emergent test.
This formulation was uniformly sprayed on 2 similar pots
containing plants 2 to 3 inches tall (except wild oats,
soybean and watergrass which were 3 to 4 inches tall)
-~ 12S~
01 -55-
(approximately 15 to 25 plants per pot) at a dose of
27.5 microgram/cm2~ After the plants had dried, they were
05 placed in a greenhouse and then watered intermittently at
their bases as needed. The plants were observad
periodically for phytotoxic effects and physiological and
morphological responses to the treatment. After 3 weeks,
the herbicidal effectiveness of the compound was rated
based on these observations. A 0-to-100 scale was used,
0 representing no phytotoxicity, 100 representing complete
kill. The results of these tests are summarized in
Table 2.
4~
o o ~n o Ln o o o o o Ln Ln Ln o Ln Ln o o o o o Ln Ln Ln o
~ ~ o ~ ~ co o r~ o ~ ~ Ln a~ ~n co o cn Ln ~ r~1
.
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01 -66-
As can be seen from the above Table l, the
compounds of the invention generally exhibit a broad spec~
05 trum of excellent pre-emergence phytotoxic activity and
: especially so Compounds Nos. 2, 4, 7, 9, 12, 14, 16, 22~
Moreover, as shown by Table 2 the compounds also generally
exhibit post-emergence phytotoxic activity against broad-
leaf plants and in some instances also against grasses,
especially so Compound Nos. 7, 9, 12, 14, 16, 22 and 23.
Also, it can be seen that the corresponding Comparison
Compounds had much poorer activity than the corresponding
compounds of the present invention.
Obviously, many modifications and variations of
the invention described hereinabove and below can be made
without departiny from the essence and scope thereof.
