Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
~s;~t7
-1- 61936-1665
~IERBICIDAL 2-(OXA OR THIA IIETEROCYCLE)5-AMINO-
3-OX0-4-~SUBSTITUTED-PHENYL)-2,3-DIHYDROFURANS
BACKGROUND OF THE INVENTInN
This invention relates to 2-(oxa and thia hetero-
cycle) 5-amino-3-oxo-4-(substituted-phenyl)-2,3-dihydrofurans and
derivatives thereof and to the use o-f such compounds as herbi-
cides and plant growth regulators.
Chemiker-Zeitung 104 (1980) No. 10, Pages 302-303,
is an academic paper disclosing the ring closure of l-(dimethyl-
amino)-2,4-diphenyl-1-buten-3,4-dione to yield 5-dimethylamino-
2,4-diphenyl-2,3-dihydrofuran. British Patent No. 1,521,092,
discloses certain 3-phenyl-5-substituted-4(1H)-pyrid-ones or
-~hiones as herbicides. Japanese Patent Application 13,710/69
(Chemical Abstracts 71:61195e) discloses 5-amino-3-oxo-4-(phenyl
or 4-chlorophenyl)-2,3-dihydrofurans. Japanese Patent No.
19090 (Chemical Abstracts 69P10352e) discloses certain 2,3-
~; dihydrothiophenes as pharmaceuticals. Helvetica Chemica Acta,
Volume 66, Pages 362-378 (1983) discloses 5-N-cyclopropyl-4-
phenyl-2-methoxycarbonyl-methylene-3-furanone as part of an
academic chemical synthesis discussion.
In my Belgian Pa~ent No. 899,931 issued
December 17, 1984, I disclosed certain 2-aryl 5-amino-3-oxo-4-
(substituted phenyl)-2,3-dihydrofuran derivatives and their
use as herbicides.
SUMMARY OF THE INVENTION
The present invention provides compounds having both
pre-emergence and post-emergence herbicidal activity and having
`~ especially good pre-emergence activity against a broad spectrum
of both broad-leaf weeds and grassy weeds. At lower application
rates the compounds also exhibit plant growth regulating
properties.
The compounds of the present invention can be re-
presented by the following formula:
,':;, ~ :' :
01 --2~
R3
05 R4 J~D
R ~ ~
~I)
wherein Rl and R2 are independen~ly hydrogen,
lower alkyl, having 1 through 4 carbon atoms, or
alkenyl having 3 through 6 carbon atoms;
R3 is hydrogen, lower alkyl, lower alkoxy, halo,
or trifluoromethyl; R4 is lower alkyl, lower alkoxy,
halo, or trifluoromethyl;
Z is a saturated or unsaturated heterocycle
radical having five or six ring atoms includiny one
or two oxygen or sulfur atoms and the remainder are
carbon atoms.
The invention also comprises compatible salts of the com-
pound of Formula (I~.
The compounds exist as keto-enol tautomer
isomers with respect to the 3-keto group shown in Formula
I. Also, where tne compounds of Formula (I) have an asym-
metric carbon atom they can exist as optical isomers. The
above formula is intended to encompass both the respective
tautomers and optical and geometric isomers where they
exist 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 of
a 3-trifluoromethyl substituent on the 4-phenyl group of
the compounds of the present invention generally very
substantially enhances herbicidal activity.
~ In a further aspect the invention provides a
`~ herbicidal composition comprising a compatible carrier and
a herbicidally effective amount of the compounds of
~0
L ?~
~1 -3-
Formula (I~, or oanpatible sal~s thereof, or mixtures
thereof.
05 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
the foliaye of such vegetation with a herbicidally effec-
tive amount of the compound(s) of Formula ~1) and/or com-
patible 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 in~ention also provides a method for
regulating plant growth ~hich comprises treating the
growth medium and/or ~he foliage of such vegetation with a
plant growth regulating effective amount o~ the com-
pound(s) of Formula (I) and/or compatible salts thereof,
effective to alter ~he normal growth pattern of said
plants.
The present invention al50 provides chemical
intermediates and processes for prsparing the compounds of
Formula ~I).
The invention will be further described herein-
below.
~ FURTHER DESC~IPTION OF THE
-~ Illustrations of typical compounds of
Formula (I) of the present invention can be had by refer-
encs to Examples 3-7 s~t forth hereinbelow on Pages 14~23.
In terms of substituents, the preferred compounds are
those wherein Rl and R2 are independently hydrogen,
methyl, ethyl or n-propyl, and more preferably one of Rl
;~ or R2 is hydrogen and the other i5 hydrogen, methyl, ethyl
or n-propyl, preferably methyl or ethyl. Preferably, R3
is hydrogen and R4 is trifluoromethyl or halo,
0
~; .
`:
~ .
3~
Ol _4_
especially trifluoromethyl~ When Rl and/or R~ is alkenyl,
preferably the alkenyl group has 3 or 4 carbon atoms.
The Z heterocycle group can be represented by
the formulas:
X~Xl X..,X
~ J and ~ ~
wherein one or two of X, Xl, x2 or X3 are indepen-
dently sulfur (divalent sulfur) or oxygen and the remain-
der is carbon atoms and the inner ring dotted lines
indicate that the ring can be saturated, unsaturated or
partially saturated. The preferred Z heterocyclic groups
are thiophene, furan, pyran and thiopyran.
The compounds of the invention wherein Rl and R2
are each hydrogen can be prepared by the following schema-
tically represented process:
~)
R3
-CH2CN + Z-C-C-ORS - > R ~ + RSOH
R4 H ~2N
wherein R3, R4, and Z are as defined herein-
above; and R5 i5 lower alkyl, aryl (e.g., phenyl) or
arylalkylene (e.g., benzyl).
This process can be conveniently effected by
contacting Compound (B) with Compound (~), and a strong
base (e.g., sodium methoxide, sodium ethoxide), preferably
in an iner~ 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 fr~m 5 to 3S hours, preferably 18 to
24 hours, using about from 1 to 10, preferably 1 to
1.2 moles of Compound ~A) per mole of Compound (B).
. ,. ~
~ 5-
;
Suitable strong bases which can be used include 7
for example, alkali metal alkanolates, for example, sodium
methoxide, sodium ethoxide, potassium ethoxide9 sodium
hydride, potassium hydride, and the like. The ~trong 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 alkanol~ (for example,
methanol, ethanol, and propanol) tetrahydr~furan,
dimethoxyethane, dioxane, and the like, and compatible
mixtures thereof. Conveniently, the alkali metal
alkanolate is prepared in situ by reacting an alkali metal
with excess alkanol which in turn serves as solvent for
the above reaction.
The starting materials of Formula tB) are
generally known materials and can be prepared by known
- procedures, or obvious modifications thereof (i.e., ~ub-
2Q stitution of appropriate starting materials). The pre-
paration of Compound (B) is for example described in
Org~ Syn. Coll., Volume l, 107 (194l).
; The hydroxy esters of Formula (A) are also
generally known compounds and can be prepared by known
;~ 25 procedures or by obvious modifications thereof (e.g., hy
using appropriately substituted starting materials). For
example, via the reaction of the corresponding hetero-
cycle-hydroxyacetonitrile with hydrogen chloride in
methanol to yield the corresponding (2-imino-2-methoxy-l-
hydroxyethyl)heterocycle hydrochloride salt which in turn
can be hydrolyzed to the corresponding ester of formula
~ A. The initial heterocycle-hydroxyacetonitrile starting
- material can be prepared via the reaction of the corre-
sponding formyl heterocycle with sodium cyanide.
The compound of Formula (I) wherein one or bo~h
of Rl and R2 are lower alkyl or lower alkenyl can be pre-
pared by alkylation ~or alkenylation) of the amino group:
:~ `
. ,~
L'7
91 6-
~f ~ R6X _ ~
(I') (I'')
wherein R3, R4 and Z are as defined hereinabove;
R6 is lower alkyl or lower alkenyl; R7 is hydrogen or
R6; and R6X' is an alkylàtion or alkenylation agent.
This process can be effected by contacting
Compound (I ' ) with a suitable alkylation or alkenylation
agent capable of alkylating or alkenyla~ing primary or
~-~ secondary amino groups,
;~ For example, this can be effected by contacting
20 Compound (I' ) with a lower alkyl iodide or lower alkenyl
iodide, preferably in an inert organic solvent and prefer-
ably 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
25 1.0 ~o 72.0, preferably 2.0 ~o 18.0 hours. Where it is
desired to alkylate or alkenylate only at R6, then typi-
cally about from 1~0 to 1~1 moles of R~I reactant is used
,~
per mole of CompGund (I'). Where it is desired to alkyl-
ate both amino hydrogens, then typically about from 1.9 to
~; 30 4.0 moles of R6l are used per mole of Compound (I'). Also
variation in R6 and R7 can be effected by first alkylation
of only one of ~he two amino hydrogens and then alkylating
the second amino hydrogen with an alkylating ayent havin~
a different R6 alkyl or alkenyl group. Suitable inert
35 organic solvents which can be used, include~ for example,
.,
liquid halogenated alkanes; for example, methylene
chloride, carbon tetrachloride, dichloroethane; tetra-
~ hydrofuran and the like. ~uitable scavenger bases
; includei for example, the bases described hereinabove with
4~ respect to the reaction of Compound ~A) with Compound (B).
, .. .
5~ 7
61936-16~5
The ~ompounds o~ Formula (I") ~7herein R is lower
alkyl ~e.g., methyl) ancl ~7 is hydrogen or lower alkyl, can be
advantageously prepared using dialkyl sulfate as the alkylating
agent. This can be conveniently effected by contacting the
compound of Formula (I') or II") with the desired lower alkyl
sulfates 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 conducted at temperatures in
the range of about frQm 0 to 100C, preferably 20 to 45C,
using about from 1.0 to 4.0 moles of dialkyl sulfate per mole
of Compound (I'). An excess, typically about 2.5 mole of base
is used. Preferablyr 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 carbona~e, and the like.
Suitable phase transfer agents are agents whi~h transfer
hydrophilic ions into a lipophilic oryanic medium and include,
for example, benzyl triethylammonium chloride, ~etra-n-
butylammonium chloride, methyltrioctylammoni.um chloride, and
;~ the like.
The compatible salts of Formula (I) can be prepared
by conventional procedures ky treating the compound of Formula
~I) wherein R1 andtor R2 is hydrogen with a suita~le strong
base such as, for example, n-butyllithium, sodium hydride,
potassium hydride, and the like, having the desired cation, by
: 30 conventiollal procedures to replace an amine hydrogen wi~h the
~ ` ~ fl 7
. ~, .
~55~:~7
61g36-1665
desired carbon. The -three-position enolate salts can be
prepared via further treatment of the amine salt with base.
Additional variati.ons in the salt cation can also be effected
via ion exchange with an ion exchange resin having the desired
cation.
General Process Conditions
In the above-described processes, it is generally
preferable to separate the respective products before
7a
,, ,~
~ . ~. /
. . ,
" '' ;
3:a7
Ol -8
proceeding with the next step in the reaction sequence,
cxcept where described as an in situ step or unless other-
05 wise expressly stated. These products can be recoveredfrom their respective reaction produet mixtures by any
suitable separation and purification procedure, such as,
for example, recrystallization and chromatography. Suit-
able ~eparation and purification procedures are, for exam-
~le, illu5tratsd in the Examples set forth hereinbelow.
Generally, the reactions described above areconducted as liquid phase reaction and hence pressure is
generally not significant except as it affects temperature
(boiling point) where reactions are conducted at reflux~
lS Therefore, these rcactions 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 reactant~, 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 scparated
by conventional separation procedures which depend upon
differences in physical properties between the geometric
isomers.
~efinitions
As used herein the following terms have the
following meanings unless expressly stated ~o the
contrary:
The term "lower alkyl" refers to both straight
and branched-chain alkyl groups having a total of from 1
through ~ r pre~erably 1 through 4, carbon atoms and
includes primary, secondary and tertiary alkyl groups.
;5~
61936-lG65
Typical lower alkyls include, for example, methyl, ethyl, n-
propyl, isopropyl, n-butyl, t-butyl.
The term "lower alkenyl" refers to alkenyl groups
having 2 through 6, preferably 2 through 4, carbon atoms and
includes, for example, vinyl, 1-propenyl, 2-propenyl,
1-methylvinyl, 1-butenyl, 2-methylprop-1-enyl and the like.
The term "halo" refers to the group of fluoro,
chloro, bromo and iodo.
The term "aryl" refers to aryl groups having 6
through 10 carbon atoms and includes, for example, phenyl,
naphthyl, indenyl, and the like.
The term "substituted aryl" refers to aryl groups
having 1 through 3 substituents independently selected from the
group of lower alkyl, lower alkoxy, halo, nitro, or haloalkyl
having 1 throuyh 3 carbon atoms and 1 through 3 halo atoms.
Typical substituted aryl groups include, for example, 2-fluoro-
phenyl, 2-chlorophenyl, 2,6-dimethylphenyl, 4-fluorophenyl,
2-methylphenyl, 2-chloro, 4-chloromethylphenyl, 2-nitro,5-
methylphenyl, 2,4-dichlorophenyl, 3-trifluoromethylphenyl,
2-methoxyphenyl, and the like.
The term "arylalkylene" or "arylalkyl" refers to the
group ArRS- wherein Ar is aryl and R5 is alkylene having 1
through 3 carbon atoms and includes both straight-chained and
branched-chained alkylenes, for example, methylene, ethyl, 1-
methylethyl, and propyl.
The term "~substituted aryl)alkylene" or "ring-
substituted arylalkylene" refers to the group Ar'R5- wherein
Ar' is substituted aryl and R5 is alkylene as defined with
respect to arylalkylene.
.
61936-1665
The term "compatible salts" refers to salts which do
not significantly alter the herbicidal properties of the parent
compound. Suitable salts include cation salts su~h as, for
example, the cation replacement salts of lithium, sodium,
potassium, alkali earth metals, ammonia, quaternary ammonium
salts, and the like.
9a
S3~7
01 --10-
The term ~room temperature" or ~ambient temper-
ature" refers to about 20-25C.
~5 ~
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
i environment (e.g., shelter~d areas such as greenhouses
~; 20 compared to exposed areas such as fields), and type and
~ degree of control desired. Generally, for both pre- and
;~ post-~mergen~ con~rol, the present compounds are applied
at rates of about from 0~02 to 60 kg/ha, preferably about
from 0.02 to lO kg/ha.
;~ 25 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 (agriculturally
acceptable carrier) is one which does not significantly
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) or mixtures thereof . Concen-
trates can also be made having high concentrations
designed for dilution prior to application, The carrier
can be a solid, liquid, or aerosol. The actual com~osi-
tions can take the form of granules, powders, dusts, solu-
tions, emulsions, slurries, aerosols, and the like.
5~7
0 1
Suitable solid carriers which can be used
include, for example, natural clays ~such a kaolin,
05 ~ttapulgite, montmorillonite, etc.), talcs, pyrophyllite,
diatomaceous silica, synthetic fine silica, calcium alumi-
nosilicate, 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, e~c.), and the like.
Suitable aerosol carriers which can be used include con-
ventional aerosol carriers such as halogenated alkanes,
etc.
The composition can also contain various promo-
ters and surface-active agents which enhance the rate of
transport of the active compound into the plant tissue
such as, for example, organic solvents, wetting agents and
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 com-
patible adjuvants, stabilizers, conditioners, insecti-
cides, fungicides, and if desired, other herbicidally
~; active compounds.
At reduced dosages the compounds of the present
invention also exhibit plant growth regulating 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 regula~ors 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 desired application, the plant growth re~ulating com-
;~ 40 position can also contain, or be applied in combination
~S~i3~
l2-
with other compatible ingredien~s such as desiccants,
defoliants, surace-active a~ents, adjuvants, fungicides,
05 and insecticides. Typically, the plant gr~wth regulating
composition will contain a total 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. Wherein, unless expressly stated to the con-
trary, all temperatures and temperature ranges refer to
the Centigrade system and the term Nambient" or Uroom
temperature" refers to about 20-25C. The term "percent"
or ~" refers to weight percent and the tenm "mole" or
moles~ refers to ~ram moles. ~he term "equivalent"
refers to a quantity of reayent equal in moles, to the
~ moles of the precedin~ or succeeding reactant rscited in
`~ 20 that example in terms of finite moles or finite weight or
volume. Where given, proton-magnetic resonance spectrum
;~ (p.m.r. or n.m.r.) were determined at 60 mHz, signals are
assigned as singlets (s), broad singlets (bs), doublets
(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.
EXA~PLES
3C Example l
. ~
In this example 25.0 y of 2-formylthiophene was
added to a stirred solution containing lO.93 9 of sodium
cyanide in 37 ml of water at room temperature. 63 ml of
3S aqueous satura~ed sodium acid sulfite was then slowly
added to the stirred mixture. During the addition of the
; sodium acid ~ulfite solution, small amounts (about 20 9)
of ice were periodically added The mixture was then
s~irred for another l~ minutes and extracted with ethyl
e~her. The ethyl ether extracts were combined, dried over
,
53~'7
01 -13-
magnesium sulfate and evaporated under vacuum affording
18.4 g of the title compound.
~xample 2
Methyl T ~
(a) In this example 6.8 9 of methanol was added
to a stirred solution of 26.9 9 of thienyl-2-yl-hydroxy-
acetonitrile in 100 ml ethyl ether at about 10C~ Hydro-
gen chloride was then bubbled through this mixture until
the formation of a salt precipitate was observed. The
mixture was then stirred for about 15 minutes at about
10C and then filtered. The filter cake was washed with
ethyl ether and then evaporated affording 18.2 g of the
chloride salt of 2-(2-imino-2-methoxy-1-hydroxyethyl)thio-
phene.
(b) The above salt was then dissolved in water
and stirred at room tempera~ure for about 30 minutes and
then extracted three ~imes with ethyl ether.
The ethyl ether extracts were combined, dried
over magnesium sulfate and concentrated by evaporation
under vacuum, affording 8.3 9 of the title compound.
The filtrate from step (a) was allowed to stand
overnight (about 16-18 hours) at room temperature and was
then filtered. The filter cake was treated as before
affording an additional 11.7 g of chloride salt. This
salt was then hydrolyzed with water as described above
affording an additional 4~4 g of the title compound.
Similarly, by applying the procedures of
Examples 1 and 2 using the a~propriate heterocyclic-
hydroxyacetonitrile star~ing material~ in Example 1, the
following compounds can be prepared.
Methyl thien-3-yl-hydroxyacetate;
Methyl(2,3 dihydrothien 2-yl~-hydroxyacetat~
Methyl tetrahydrothien-3-yl-hydroxyacetate;
Methyl(2H-thiopyran-2-yl)-hydroxyacetate
Methyl fur-2-yl-hydroxyacetate;
Methyl fur-3-yl-hydroxyacetate;
Methyl(2,3-dihydrofur-2-yl)-hydroxyacetate;
Methyl tetrahydrofur-3-yl hydroxyacetate;
~X~
01 -14-
Methyl~4H-pyran-2-yl) hydroxyacetate;
Methyl(2H 3,4-dihydropyran-3 yl)-hydroxyacetate; and
05 Methyl(tetrahydropyran-2-yl)-hydroxyacetateO
Example 3
2-Thien-2-yl-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2 3-dihvdrofuran
A dry, 250-ml, three-neck, round-bottom flask
equipped with a mechanical stirrer, addition funnel and a
reflux condenser bearing a nitrogen inlet tube was charged
~ with 4.2 ~ of sodium and lO0 ml of absolute ethanol. To
i~ the resulting sodium ethoxide solution was added dropwise
~ a mixture of 21 o l g Of methyl thien-2-yl hydroxyacetate
;~ 15 and 22.7 g of m-trifluoromethylphenyl-acetonitrile in
20 ml of ethanol. The resulting mixture was heated at
reflux for 4-5 hours after which time it was added to
300-400 ml of water and extracted with petroleum ether.
The aqueous phase was acidified with aqueous lO weiyht
percent hydrochloric acid and extracted two times with
diethyl ether. The ether extracts were washed twice wi~h
~; saturated aqueous sodium bicarbonate, dried over magnesium
sulfate and concentrated in vacuo to yield a thick dark
oil~ This oil was triturated with 20-30~ ether/petroleum
ether which afforded 4.9 9 of the ~itle compound as a tan
powder.
Similarly, by applying the above-described pro-
cedure using the appropriate (substituted phenyl) aceto-
nitrile starting materials the following eompounds can
also be prepared:
2-(thien-2-yl)-3-oxo-4-~5-ehloro-3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4-chloro-3-~rifluoromethyl-
phenyl)-5-amino-2,3 dihydrofuran;
2-(thien-2-yl)~3-oxo-4-(2-bromo-3-trifluoromethyl-
~` phenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-[6-fluoro--3 trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4 methyl-3-trifluoromethyl-
phenyl)-5-amino 2,3 dihydrofuran;
.~
~53~7
01 -15-
2-(thien-2 yl)-3-oxo-4-(5-methoxy-3-trifluoromethyl-
phenyl)~5-amino-2,3 dihydrofuran;
05 2-(thien-2-yl)-3-oxo-4-(6-isopropyl-3-trifluoro-
methylphenyl)-5-amino-2,3-dihydrofuran
2-(thien-2-yl)-3-oxo-4-(3,5-di-trifluoromethylphenyl~-
5-amino-2,3-dihydrofuran;
2-(thien-2-yl) 3-oxo-4-(3-propylphenyl)-5-amino-2,3-
dihydrofuran;
2-~thien-2-yl)-3-oxo-4-(3-methylphenyl)-S-amino-2,3-
dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-fluorophenyl)-5-amino-2,3-
dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-methoxy~henyl)-5-amino-2,3-
dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-iodophenyl)-5-amino-2,3-
dihydrofuran; and
2-(thien-2-yl)-3-oxo-4-(2-chloro-3-methylphenyl)-5-
amino-2,3-dihydrofuran;
2-~thien-2-yl)-3-oxo-4-(4-ethyl-3-methylphenyl)-5-
amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-~5-methoxy-3-chlorophenyl)-5-
amino-2,3-~ihydrofuran;
2-(thien-2-yl)-3-oxo-4-(6-ethoxy-3-chlorophenyl)-5-
amino-2,3-dihydrofuran;
2-(thien-2-yl)-3~oxo~4-(3,5-diethoxyphenyl)-5-amino-
2,3-dihydrofuran;
~: 2-(thien-2-yl)-3-oxo-4-(3-brsmophenyl)-5-amino-2,3-
; 30 dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-chloro-4-methylphenyl)-S-
~ amino-2,3-dihydrofuran;
: 2-(thien-2-yl)-3-oxo-4-(3-bromo-2-ethylphenyl)-S-
amino-2,3-dihydrofuran;
2-~thien-2-yl)-3-oxo-4-(3,6-dimethylphenyl)-5-amino-
2,3--dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-iodo-4-methylphenyl)-5-
amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-chlorophenyl)-5-amino-2,3-
dihydrofuran;
.,,
~l~2S53~7
01 -16-
2-(thien-2-yl)-3-oxo-4-~3-butylphenyl)-5-amino-2,3-
dihydrofuran;
05 2-(thien-2-yl)-3-oxo-4-(3-butoxyphenyl)-5-amino-2,3-
dihydrofuran; and
2-~thien-2-yl)-3-oxo-4-(3-isvpropoxyphenyl)-5-amino-
2,3-dihydrofuran.
Similarly by applying the above procedure using
the appropriate (substituted phenyl)acetonitrile and the
appropriate methyl heterocycle-hydroxyacetate compound of
the list given in Example 2 the corresponding 2~hetero-
cycle analogs of the a~ove compounds can also be prepared
for example:
;~ 2-~thien-3-yl)-3-oxo-4-(3-bromophenyl)-5-amino-2,3-
dihydrofuran;
2-(thien-3-yl)-3-oxo-4-t3-iodophenyl)-5 amino-2,3-
dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-propylphenyl)-5-amino-2,3-
2U dihydrofuran;
2-(thien~3-yl~-3-oxo-4-(3-methoxyphenyl) 5-amino-2,3-
dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-fluorophenyl)-5-amino-2,3-
dihydrofuran; and
~5 2-(thien-3-yl)-3-oxo-4-(3-propoxyphenyl)-5-amino-2,3-
dihydrofuran.
2-(thien-3-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-
amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-chlorophenyl)-5-amino-2,3-
~ 30 dihydrofuran;
- 2-(2,3-dihydrothien-2-yl)-3-oxo-4-(3-trifluoromethyl-
: phenyl)-5-amino-2,3-dihydrofuran;
2-(2,3-dihydrothien-2-yl)-3-oxo-4-(3,5-diethoxy-
~ phenyl)-5-amino-2,3-dihydrofuran;
~ 2-(tetrahydrothien-3-yl)-3-oxo-4-~3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-(?H-thiopyran-2-yl)-3-oxo-4-(3-bromophenyl)-5-
amino-2,3-dihydrofuran;
2-(2H-thiopyran-2-yl)-3-oxo-4-(2-chloro-3-trifluoro-
methylphenyl)-5-amino-2,3-dihydrofuran,
~S~3~'7
01 -17-
2-~fur-~-yl)-3 oxo-4-t3-trifluoromethyl-5-chloro-
phenyl)-5-amino-2,3-dihydrofuran;
05 2-(fur-2-yl)-3-oxo-4-(3-fluorophenyl)-5-amino-2,3-
dihydrofuran;
2-(fur-2-yl)-3~oxo-4-(3-bromophenyl)-5-amino-2,3-
dihydrofuran;
2-(fur-2-yl)-3-oxo-4-(3-chlorophenyl)-S-amino-2,3-
dihydrofuran;
2-(fur-2 yl)-3-oxo-4-(3-methylphenyl~-5-amino-2/3~
dihydrofuran;
2-(ur-2-yl)-3-oxo 4-(2-butoxy-3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
2-(fur-2-yl)~3-oxo-4-(3-trifluoromethylphenyl~-5-
amino-2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4-(3-iodophenyl)-5-amino-2,3-
dihydrofuran;
2-(fur-2-yl~-3-oxo-4-(3-pro~ylphenyl)-S-amino-2,3-
dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-oxo-4-(3-trifluoromethyl-
~ phenyl)-5-amino-2,3-dihydrofuran;
`~ 2-(2,3-dihydrofur-2-yl)-3-oxo-4-(2-bromo-3-trifluoro-
methylphenyl)-5-amino-2,3-dihydrofuran;
2-(tetrahydrofur-2-yl)-3-oxo-4-(3-trifluoromethyl-
. phenyl)-5-amino-2,3-dihydrofuran;
2-(tetrahydrofur-2-yl)-3-oxo-4-(4-me~hyl-3-tri~luoro-
methylphenyl)-5-amino-2,3-dihydrofuran;
~ 2-(fur-3-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-
:: 30 phenyl~5-amino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-fluorophenyl)-S-amino-2,3-
dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-bromophenyl)-5-amino-2/3-
dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-chlorophenyl)-S-amino-2,3-
dihydrofuran;
2~fur-3-yl)-3-oxo-4-(3-methylphenyl)-5-amino-2,3-
dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(2-butoxy-3-~rifluoromethyl-
p~enyl)-5-amino-2,3-dihydrofuran;
.,
~2~53~
~1 -18-
2-~ur-3-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-
amino-2,3-dihydrofuran;
05 2- ( f ur-3-yl)-3-oxo-4-(3-methoxyphenyl)-5-amino-2,3-
dihydrofuran;
2-lfur-3-yl)-3-oxo-4-(3-ethylphenyl)-5-amino-2,3-
dihydrofuran;
2-~2,3-dihydrofur-2-yll-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2r3-dihydrofuran;
2-~2,3-dihydrofur-2-yl)-3-oxo-4-(2-bromo-3-trifluoro-
methylphenyl)-5-amino-2,3-dihydrofuran;
2-(tetrahydrofur-3-yl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-amino-2,3-dihydrofuran;
~ 15 2-(tetrahydrofur-3-yl)-3-oxo-4-(4-methyl-3-trifluoro-
: methylphenyl)-5-amino-2,3-dihydrofuran;
2 (4H-pyran-2-yl)-3-oxo-4-(3-trifluoromethylphenyl)-
5-amino-2~3-dihydrofuran;
2-~4H-pyran-2-yl)-3-oxo-4-~3-fluorophenyl3-5-amino-
2,3-dihydrofuran;
2-~4H-pyran-2-yl)-3-oxo-4-(3-methylphenyl)-5-amino-
2,3-dihydrofuran;
2-(4H-pyran-2-yl)-3-oxo-4-(2-methyl-3-trifluoro-
methylphenyl)-5-amino-2,3-dihydrofuran;
2-(4H-pyran-2-yl)~3-oxo-4-(2-nitro-3-methylphenyl)-5-
amino-2 r3-dihydrofuran;
2-~2H-3,4-dihydropyran-3-yl)-3-oxo-4-(3-trifluoro-
methylphenyl)-5-amino-2,3-dihydrofuran;
2-~2H-3,4-dihydropyran-3-yl~-3-oxo-4-~2-chloro-3-
~: 30 trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-~-2H-3,4-dihydropyran-4-yl)-3-oxo-4-(3-fluoro-
phenyl) 5-amino-2,3-dihydrofuran;
2-~2H-3,4-dihydropyran-3-yl)-3-oxo-4-(2-chloro-3-
~: methylphenyl~-5-amino-2,3-dihydrofuran;
~ 2-(tetrahydropyran-2-yl)-3-oxo-4-(3-trifluoromethyl-
~ phenyl)-5-amino-2~3-dihydrofuran;
:~ 2 tetrahydropyran-2-yl-3-oxo-4-(3-chloro-5-methyl-
: phenyl)-5-amino-2,3-dihydrofuran;
2-( tetrahydropyran-2~yl ) -3 oxo-4- ( 3-fluorophenyl)-5-
~ amino-2,3-dihydrofuran; and
.~
~1936-1665
2-ltetrahydropyran-2-yl)-3-oxo-4-l3-ethylphenyl)-5-amino-
~,3-dihydrofuran.
Example 4
2-Thien-2-yl-3-oxo-4-(3-trifluoromethylphenyl)-
_ _ 5-methylamino-2~3-dihydrofuran
In thi~ example about 0.36 g of ~olid sodium
hydroxide was dissolved in a small amount oE water and then
added to 100 ml of methylene ~hlorid~ containin~ 1.4 g of 2-
thien-2-yl-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2,3-
dihydrofuran. 0.20 g of benzyltriethylammonium ~hloride was
added and then a mixture containing O.B4 ml of dimethyl sulfate
in a~out 5.0 ml of methylene chloride was slowly added at room
temperature. The mixture was stirred at room temperature for
about one hour and then washed twice with water, twice with
N. aqueous hydrochloric acid, twice with sodium bicarbonate,
dried over magnesium sulfate and then concentra~ed by
evaporation under vacuum. The residue was then triturated in a
mixture of ethyl ekher and petroleum ether affording 1.4 g of
the title compound.
Similarly, by following the ~ame procedure usiny the
products listed ln Example 3 as starting materials, the
corresponding 5-methylamino homoloys thereof can be prepared,
for example:
2-(thien-2-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4-chloro-3-tri~luoromethyl-
phenyl)-5 methylamino-2,3-dihydrofuran;
2-l~hien-2-yl)-~-oxo-4-(2-bromo-3-triiluoromethylphenyl)-
5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-~6-fluoro-3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
~ 19
61936-1665
2-(~hien-2~yl)-3-oxo-4-(4-methyl~3-trifluoromethylphenyl)-
5-methylamino-2,3~dihydrofuran;
2-(thien-2-yl)-3-oxo-4(5-methoxy-3-trifluoromethylphenyl)-
5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(6-isopropyl-3-
trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
r l9a
~5~7
01 -20-
2-~thien-2-yl)-3-oxo-4-(3,5-di-trifluoromethyl-
phenyl)-S-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-propylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-methylphenyl)~5-
methylamino-2,3 dihydrofuran;
2-(thien-2-yl)~3-oxo-4-(3-fluorophenyl)-S-methyl-
amino-2,3-dihydrofuran;
2 (thien-2-yl)-3-oxo-4-(3-methoxyphenyl)-5-
methylam.ino-2~3-dihydrofuran;
2-(thien 2-yl)-3-oxo-4-(3-iodophenyl)-5-methylamino-
2,3-dihydrofuran; and
~ lS 2-(thien-2-yl)-3-oxo-4-(2-chloro-3-methylphenyl~-5-
: methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4-ethyl-3-methylphenyl)-S-
methylamino-2,3-dihydrofuran;
~ 2-~thien-2-yl)-3-oxo-4-(5-methoxy-3-ehlorophenyl)-S-
; 20 methylamino-2,3-dihydrofuran;
2 (thien-2-yl)-3-oxo-4-(6-ethoxy-3-chlorophenyl)-5-
methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3,5-diethoxyphenyl)-5-methyl-
- amino-2,3~dihydrofuran;
~5 2-tthien-2-yl)-3-oxo-4-(3-bromophenyl)-5 methylamino-
2 t 3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-chloro-4-methylphenyl~-S-
: methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-bromo-2-ethylphenyl)-S-
methylamino-2,3-dihydrofuran;
. 2-(thien-2-yl)-3-oxo-4-(3,6-dimethylphenyl)-5-methyl-
amino 2,3-dihydrofuran;
2-(thien-2-yl)-3~oxo 4-(3-iodo-4-msthylphenyl)-5-
methylamino-2,3-dihydrofuran;
2 (thien-2-yl)-3-oxo-4 (3-chlorophenyl~-5 methyl-
amino~2,3-dihydrofuran;
~-~thien-2-yl)~3~oxo-4-(3-butylphenyl)-5-methylamino-
2,3-dihydrofuran;
2-(thien-2-yl~-3-oxo-4-(3-butoxyphenyl)-5-methyl-
~ amino-2,3-dihydrofuran;
~Z55~
01 -21-
: 2-(thien-2-yl)-3-oxo-4-(3-isopropoxyphenylj-5-methyl-
amino-2,3-dihydrofuran;
05 2-(thien-3-yl)-3-oxo-4-~3-bromophenyl)-5-methylamino-
2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4 (3-iodophenyl)-5-methylamino-
2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(2-methylphenyl)-5-methyl-
amino-2,3-dihydrofuran;
2-(thien-3-yl~-3-oxo-4-(3-methoxyphenyl)-5-methyl-
amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-fluorophenyl)-5-methyl-
amino-2,3-dihydrofuran;
; lS 2-(thien-3-yl)-3-oxo-4-(3-propoxyphenyl)-5-methyl-
amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-chlorophenyl)-5-methyl-
amino-2,3-dihydrofuran;
2-(2,3-dihydrothien-2-yl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrothien-2-yl)-3-oxo-4~(3,5-diethoxy-
~ phenyl)-5-methylamino-2,3-dihydrofuran;
: 25 2-(tetrahydrothien-;3-yl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-(2H-thiopyran-2-yl)-3-oxo-4-(3-bromophenyl)-5-
~ methylamino-2,3-dihydrofuran;
- 2-(2H-thiopyran-2-yl)-3-oxo-4-(2~chloro-3-trifluoro-
methylphenyl)-5-methylamino-2,3-dihydrofuran;
~ 2-(fur-2-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-
;:` phenyl)-5-methylamino-2,3-dihydrofuran,
2-(fur-2-yl)-3-oxo-4-(3-fluorophenyl)-5-methylamino-
2,3-dihydrofuran;
2-(fur-2-yl3-3-oxo-4-(3-bromophenyl)-S-methylamino-
2,3-dihydrofuran;
2 (fur-2-yl)-3-oxo-4-(3-chlorophenyl)-5-methylamino-
2,3-dihydrofuran;
~-(fur-2-yl)-3-oxo-4-(3-m2thylphenyl)-5-methylamino-
~ 2,3-dihydrofuran;
SS3~7
~1 -22-
2-(fur-~-yl)-3-oxo-4-(2-butoxy-3-trifluorome~hyl-
phenyl)-5-methylamino-2,3-dihydrofur~n;
oS 2-(fur-2-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4-(3-iodophenyl)-5-methylamino-
2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4 13-propylphenyl)-5-methylamino-
2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-oxo-4-(3-trifluoromethyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-oxo-4-(2-bromo-3-trifluoro-
methylphenyl)-5-methylamino-2,3-dihydrofuran;
lS 2-(tetrahydrofur-2-yl~-3-oxo-4-(3-trifluoromethyl-
:` phenyl)-5-methylamino-2,3-dihydrofuran;
: 2-(tetrahydrofur-2-yl)-3-oxo-4-l4-methyl-3-trifluoro-
; methylphenyl)-5-methylamino~2,3-dihydrofuran;
~: 2-(fur-3-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-
~0 phenyl)-5-methylamino-2,3-dihydrofuran
2-(fur-3-yl)-3-oxo-4-l3-fluorophenyl)-5-methylamino-
2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-bromophenyl)-5-methylamino-
~; 2,3-dihydrofuran;
` 25 2-(fur-3-yl)-3-oxo-4~(3-chlorophenyl)-5-methylamino-
2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-methylphenyl)-5-methylamino-
:~ 2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(2-butoxy~3-trifluoromethyl-
phenyl)-5 methylamino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-trifluoromethylphenyl~-5-
methylamino-2,3-dihydrofuran;
2- ( f ur-3-yl)-3-oxo-4-(3-methoxyphenyl)-5-methylamino-
2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-ethylphenyl)-5-methylamino-
2,3-dihydrofuran;
2-~2~3-dihydrofur-2-yl~-3-oxo-4-(3-trifluoromethyl-
phenyl)~5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-vxo~4-l2-hromo-3-trifluoro-
methylphenyl)-5-methylamino-2,3-dlhydrofuran;
S3~7
01 -23~
2-~tetrahydrofur-3-yl)-3 oxo-4-(3-~rifluoromethyl~
phenyl)-5-methylamino-2,3-dihydrofuran;
05 2-~tetrahydrofur-3-yl)-3-oxo-4-(4-methyl-3-trifluoro-
; methylphenyl)-5-methylamino-2,3-dihydrofuran,
2-~4H-pyran-2-yl)-3-oxo-4-(3-trifluoromethylphenyl~-
5-methylamino-2,3-dihydrofuran;
2-~4H-pyran-2-yl)-3-oxo-4-(3-fluorophenyl)-5-methyl-
amino-2,3-dihydrofuran;
2~(4H-pyran-2-yl)-3-oxo-4-(3-methylphenyl)-5-methyl-
amino-2,3-dihydr3furan;
: 2-(4H-pyran-2-yl)~3-oxo-4-(2-methyl-3-trifluoro~
methylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(4H-pyran-2-yl)-3-oxo-4 (2-nitro-3-methylphenyl)-5-
methylamino-2,3-dihydrofuran;
2-(2H-3,4-dihydropyran-3-yl)-3-oxo-4-(3-trifluoro-
methylphenyll-5 methylamino-2,3-dihydrofuran;
2-(2H-3,4-dihydropyran-3-yl)-3-oxo-4-(2-chloro-3
trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(2H-3,4-dihydropyran-3-yl~-3-oxo-4-(3-fluoro-
:~ phenyl)-5-methylamino 2,3-dihydrofuran;
: 2-(2H-3,4-dihydropyran-4-yl)-3-oxo-4(3-methylphenyl)-
5-methylamino-2,3-dihydro~uran;
2-(tetrahydropyran-2-yl)-3-oxo-4-(3-~rifluoromethyl-
phenyl)-5-methylamino-213-dihydrofuran;
2-(tetrahydropyran-2-yl)-3-oxo-4-(3-chloro-5-methyl-
phenyl)-5-methylamino-2,3-dihydrofuran;
2-(tetrahydropyran-3-yl)-3-oxo-4-(3-fluoroyhenyl)-5-
methylamino-2,3-dihydrofuran; and
2-(tetrahydropyran-4-yl)-3-oxo-4-(3-ethylphenyl)-5-
methylamino-2,3-dihydrofuran.
Example 5
2-(Thien-2-yl)-3-oxo-4-(3-trifluoro-
methylp_~yl)-5-allylamino-2,3-dlhydrofuran
This example illustrates a preparation which can
be used to prepare the 5-allylamino substituted compounds
of the invention.
~S3;~'7
~1 -24-
One gram of sodium hydroxide in 4.0 ml of water
is added to a mixture of 1 mmol of 2-(thien 2-yll-3-oxo-4-
05 (3 trifluoromethylphenyl)-5-amino-2,3-dihydrofuran in 80
ml of methylene chloride at room temperature followed by
the addition of 1 mmol of allyl bromide and 0.27 9 of
benzyltriethylammonium chloride The resulting mixture is
stirred at room temperature for about 18 hours after which
time it can be washed three times with water, dried over
magnesium sulfate and concentrated in vacuo. The residue
can ~e purified by chromatography over silica gel to yield
the title compound.
Similarly, by applying this procedure to the
products listed in Examples 3 and 4, the corresporlding
5-allylamino analogs thereof can bs prepared. Similarly,
by approximately doubling the amount of allyl bromide and
sodium hydroxide, the corresponding 5-diallylamino analogs
thereof can be prepared.
In a like manner, by using ethyl bxomide in
place of allyl bromide, the corresponding 5-ethyl and
5-diethyl analogs can be prepared.
Similarlyl by using the 5-methylamino analogs of
Example 4 as starting materials, the corresponding 5-N-
methyl-N-allylamino and 5-N-methyl-N-ethyl analogs can be
prepared.
~ ~e~
Lithium salt of 2-thien 2-yl-3-oxo-
4-(3-trifluoromethylphenyl)- `
5-methylamino-2,3-dihydrofuran (R~ R2-Li)
This example illustrates a preparation which can
be used to prepare the lithium salts of the invention.
In this example, 5.4 ml of 1.6M n-butyllithium
in hexane i5 added dropwise to a stirred solution contain-
ing 2.al 9 of 2-thien-2-yl-3-oxo-4-(3-trifluoromethyl-
phenyl)-5 amino-2,3-dihydrofuran in 25 ml of tetrahydro-
furan at -30C. The mixture is stirred for 20 minutes and
can ~hen be concentrated by evaporation ln vacuo to yield
the title compound.
,
i! ;2~53~
01 ~-25-
Similarly, by following the same procedure, the
corresponding lithium salts of the compounds of
05 Examples 3-5 can bs prepared.
Example 7
The compounds listed in Table A hereinbelow were
prepared using the appropriate starting materials and pro-
cedures described in the Examples hereinabove.
`~ ~0
I
,
~: 35
:
~2S~3~L7
* #er
~ ~ ~ er
.~ C ~,
.,, o
, o ~o _, ~ Ul U~
a~ ~ ~ ~r
~: , ,, ~ ~ ,
:, ~c ~
r~
o .....
g ~ ~r er eP ~r
~ .
., ~,
Z _, ~ _, ~ _, ~
cn O ~
U~
¢ ~ ~
Z ~ ~ ~ ~ ~ ~ _,
~ ~ o . . . . .
o
~ ~ .
~ ~ Z ~C ~ O~n0~r~
c~
I ~ /Z~
/ ~ \ N r-lC O ~ ~ Lf') ~ CO
~ ~ Ln
~ t~ c~
.
f~
~ ~c s
a~
s ~c s s ~
J~
3 3 ~ ~ O
~ O
ol
Z I ~ ~
Ln O U- o Ul
o ~7 ~ _I ~ ~
~:
3L~S5~
~l -27-
~.
In this example, the compounds of Table A were
05 respecti~ely 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 Table A 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:
35515 mg of test compound was dissolved in 15 m~
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
~; 20 of 625 mg/l.
Seeds of the test veyetation were planted in a
pot of soil and the test solution was sprayed uniformly
onto the soil surface either at a dcse of 27.5 micro-
grams/cm2. The pot was watered and placed in a green-
house. The pot was watered intermittently and observed
for seedling emergence, health of emerging seedlings,
etc., for a 3-week periodO At the end of this period, the
herbicidal effectiveness of the compound was rated based
on the physiological observations~ A 0-to-lO0 scale was
used, 0 representing no phytotoxicity, lO0 representing
complete kill. The results of these tests are summarized
in Table l.
Post-Emergent Herbicidal Te~t
The test compound was formulated in the same
manner as described above for the pre-emergent ~est.
This formulation was uniformly sprayed on 2 similar pots
containing plants ~ to 3 inches tall (except wild oats,
soybean and watergrass which were 3 to 4 inches tall)
~approximately 15 to 25 plants per pot) at a dose of
27.5 microgram/cm~. After the plants had dried, they were
.
~2S~i3~7
01 -28-
placed in a greenhouse and then watered intermittsntly at
their bases as needed. The plants were observed periodic-
o~ ally for phytotoxic effects and physiological and morpho-
logical 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.
TABLE 1
Pre-Emergence Herbicidal Activity
Application Rate: 27.5 micrograms/cm2,
unless otherwise noted
Broad~Leaf Plants Grasses
Com-- % Ph~toxicity ~ 3~959~19~ ~
pound Lambs- Pig Soy Crab Water Wild
: No. _ 5~ Mustarù weed bean 9~ grass Oats Rice
1 , 100 100 100100 100 100 99 g7
2 100 100 100100 100 100 100 99
3 100 10~ 10090 100 100 100 100
4 100 100 100100 1~0 100 100 100
100 100 1009S 100 100 100 98
TA~LE 1
Application Rate: 27.5 micrograms/cm29
: 30 unless otherwise noted
Broad-Leaf Plants Grasses
Com- % Phytotoxicity_ % Phytotoxicity
~ pound Lambs- Pig Soy Crab Water Wild
: No. ~uart r Mustard weed bean ~rass 9~ Oats Rice
1 ~5 9g ~8 38 45 60 65 30
2 93 100 90 75 58 70 75 40
~:; 3 70 90 65 70 80 60 75 25
~ 4 Not Test0d
: 5 85 95 70 90 70 90 93 70
::~ 4~
~;~5S3~7
01 -29-
As can be seen from the above Table 1, the tes~
compounds of the invention exhibited a broad spectrum of
oS excellent pre-emergence phytotoxic activity. Moreover, as
shown by Table 2 the compounds also exhibit a broad spec-
trum of post-emergence phytotoxic activity and especially
so Compound No. 2.
: Obviously, many modifications and variations of
the invention described hereinabove and below can be made
without departing from the essence and scope thereof.
:: 2
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