Note: Descriptions are shown in the official language in which they were submitted.
495;~Z
l-THIADIAZOLY -6-ACYLOXYTETRAHYDROPYRIMIDINONES
Specification
This invention relates to new compositions of
matter and more specifically relates to new chemical compounds
of the formula 3 --
O - R - :
N - t~
~ C~l- C
P~ - C C ~ N C~
\ / \ / '
S C - N
1~ 12 tl)
wherein ~1 is select~d fro~ the group consistin~ of alkyl,
alkenyl, haloal~yl, alkoxy, alkylthio, alkylsulfonyl, alkyl-
sul~inyl and cycloalkyl; R2 is selected from the group consi.sting
o~ alkyl, alkenyl, haloalkyl and
R4 ~ :
:; :
- C - C _ CH ~ ::
wherein R4 and RS are each se].ected from the group consisting
of hydrogen and alkyl; and R3 is selected from the group con-
sisting of hydrogen and
O
11 ~6
wherein R6 is selected from the group consisting o~ alkyl,
haloalkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl and
Xn . 1-
~ (CH2 ~ m ~ . ; ~
H~5-n) - ~-
wherein X.is selected from the group consisting of alkyl, halo~en,
haloalkyl~ nitro, cyano and alkoxy, and m and n are each integers
~rom O to 3
,~ ,
. ' ~ , ''' ~',' ' '"
,
_ _ . . . ~ _ , . . .
52~ ::
In a preferred embodiment of the present invention
R is selected from the group consisting of lower alkyl, lower
alkenyl, lower chloroalkyl, lower bromoalkyl, trifluoromethyl,
lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkyl-
sulfinyl and cycloalkyl of from 3 to 7 carbon atoms; R2 is
selected from the group consisting of lower alkyl, lower alkenyl,
lower chloroalkyl, lower bromoalkyl and
R4
~ ~ C _ CH
R
wherein R4 and R5 are each se].ected from the group consisting ~ -
of hydrogen and lower alkyl; and R3 is selected from the group
consisting of hydrogen and
O
'- C - R6 " , ,.
wherein R6 is selected from the group consisting of lower al~yl,
lower chloroalkyl, lower bromoaikyl, lower alkenyl, lower alkynyl,
lower alkoxyalkyl, cycloalkyl of from 3 to 7 carbon atoms and
n
(CH2)m ~
H(5-n) -
wherein X is selected from the group consisting of lower alkyl,
lower alkoxy, halogen and lower haloalkyl, and m and n are each
integers from 0 to 3.
~he term "lower" as used herein designates a straight
or branched carbon chain of up to six carbon atoms~ .
The compaunds of tha present invention are unexpectedly
useful as herbicides
The compounds o~ this invention wherein R3 is
. o
,~, , , ' ' .
.
",'" '. , ~ '' `,
3L~4~5'~Z
and R6 is as heretofor~ described, can be prepared by reacting
a corresponding compound of this invention, wherein R3 is
hydrogen, of the formula
011
N N
11 11 ~C~I--C~
R - C C - N Cll
\ S / C / 2
Il I .
O R- (II)
wherein Rl and R2 are as heretofore described, with an acid
anhydride O r the formula
O O ., ,' '
R6 _ C - - 11 - R6 (III)
wherein R6 is as heretofore described, in the presence of a
catalyLic amount of ~oluenesulfonic acid. This reaction can
be effected by combining the reactants and the catalyst at room
temperature in an inert organic reaction medium and then heating
the réaction mixture on a steam bath at a temperature o~ from.
S0 to 90C with stirring for a period of from 1/2 to 4 hours.
After this time the reaction mixture can be cooled and the desired
product can be recovered by filtration if ~ormed as a precipitate ~:
or upon evaporation of the organic reaction medium if soluble
therein. In some instances the acid anhydride can be used as
.a solvent for the compound of ormula II, obviating the use
of an inert solvent as the reaction medium. When lower alkanoic
anhydrides are used, water can be added to the reaction mixture
to precipitate the desired product upon completion o the
~reaction. The product can then be purified by conventional
~ means such as recrystallization ana the like.
~he compound of this invention wherein R3 is .
.
. o C - R ~ ~ ;
'
. '
~95ZZ
can also be prepared by reacting the compound of formula II with
an acid halide of the formula
Cl - ~ - R6 (IV)
wherein R6 is as heretofore described, in the presence of an
acid acceptor such as a *ertiary amine. The preparational
method can be utilized when the desired anhydride of formula III
is not available. This reaction can be effected by slowly adding
the acid chloride of formula IV, with stirring, to a solution
of an about equimolar amount of the compound of formula II in
an inert organic solvent, in the presence of an acid acceptor,
at a temperature of abou-t 10 to 30C. After the addition is
completed, the reaction mixture can be heated at a temperature
ranging up to the reflux temperature of the mixture to ensure
completion of the reaction. The desired product can th~n be
recovered by first filtering the reaction mixture to remove
acid acceptor chloride, followed by stripping off the solvent
i~ the product is soluble therein, or , if ~ormed as a precipitate,
by filtration and subsequent washing and purification.
The compounds of this invention wherein R is hydrogen
can be prepared by heating aaompound of the formula
N N
.. Il 11 oR7
R~ C - N ~ C - N ~ CH2 - CH2 - CH
~ / H R2 ~R8 (V)
wherein Rl and R2 are as heretofore described and R7 and R8
are methyl or ethyl, in a dilute 3 aqueous, acidic reaction
medium for a period of about 10 to about 60 minutes. Tempera-
tures of from about 70C to ~he reflux temperature of the reaction
mixture can be utilized. The reaction medium can comprise a
dilute aqueous inorganic acid such as hydrochloric acid at a
concentration of from about 0.5 to about 5 percent. Upon com
pletion of the reaction the desired product can be recovered
~4~35ZZ
as a precipitate by cooling the reaction mix-ture. This product
can be used as such or can be further purified by conventional
means such as recrystallization and the like.
The compounds of formula IV can be prepared by reacting -
a molar amount of an isocyanate dimer of the formula
N N
¦ 0 = C = N _ C I -
2 (VI)
wherein R-l is as heretofore described, with about two molar ~
amounts of an acetal of the formula --
oR7
H - N - CH2 - CH2 - CH
R2 oR8 (VII)
wherein R2, R7 and R8 are as heretofore described. This reaction
can be effected by heating a mixture of the isocyanate dimer
and the acetal in an inert organic reaction medium such as henzene
at the reflux temperature of the reaction mixture. Heating at
reflux can be continued for a period of form about 2 to about
30 mi~utes to ensure completion of the reac~ion. After this
time the desired product can be recovered upon evaporatîon
of the reaction medium and can be used as such or can be further
purified by standard techniques in the art.
'~he isocyanate dimer of formula VI can be prepared
by reacting a thiadiazole of the formula
~ N
R~ _ ~\ /C - NH2'
S (VIII)
wherein Rl is as`heretofore described, with phosgene. This
reaction can be effected by adding a slurry or solution of the
thiadiaæole, in a suitable organic solvent such as ethyl acetate,
to a saturated solution of phosgene in an organic solvent such
~4952;~
as ethyl acetate. The resulting mixture can be stirred at
ambient temperatures for a period of ~rom about 4 to about 24
hours. The reaction mix-ture can then be purged with nitrogen
gas to remove unreacted phosgene. The desired product can then
be recovere~ by filtration if formed as a precipitate or upon
evaporation of the organic solvent used if soluble therein.
This product can be used as such or can be further purified
if desired.
Exemplary thiadiazoles of formula VIII useful for
preparing the compounds of the present invention are 5-methyl-
2-amino-lg3,4-thiadiazole, 5-ethyl-2-amino-1,3,4-thiadiazole,
5-propyl-2-amino-113,4-thiadiazole, 5-allyl-2-amino-1,3,4 `
thiadiazole, 5-pent-3enyl~2-amino-1,3,4-thiadiazole, 5-chloro-
methyl-2-amino-1,3,4-thiadiazole, 5-0-chloroethyl-2-amino-
1,3,4-thiadiazole, 5-~-chloropropyl-2-amino-1~3,4-thiadiazole,
5-trichloromethyl-2-amino-1,3,4-thiadiazole, 5-methoxy-2 amino-
1,3,4-thiadiazole, 5-ethoxy-2-amino-1,3,4-thiadiazole, 5-
propoxy-2-amino-1,3,4-thiadiazole, 5-butyloxy-2-amino-1,3,4-
thiadiazole, 5-hexyloxy-2-amino-1,3,4-thiadiazole, 5-methylthio-
2-amino-1,3,4~thiadiazole, 5-ethylthio-2-amino-1,3,4-thiadiazole,
5-propylthio-2-amino-1,3 7 4-thiadiazole, S-butylthio-2-amino-
1,3,~_thiadiazole, 5-methylsulfonyl-2-amino-1,3,4-thiadiazole,
S-ehtylsulfonyl-2-amino~1,3,4-thiadiazole, 5-butylsulfonyl-2-
amino-1,314-thiadiazole, 5-methylsulfinyl-2- amino-1,3,4-thiadia-
zole, 5-ethylsulfinyl-2-amino-1,3,4-thiadiazole, 5-propylsulfinyl-
2-amino-1,3,4-thiadiazole, 5-t-butyl-2-amino-1,3,4-thiadiazole,
5-trifluoromethyl-2-amino-1,394-thiadiazole, 5-cyclopropyl-2- ;
amino-1,3,4-thiadiazole, 5-cyclobutyl-2-amino-1~3-~4-thiadiazole,
5-cyclopentyl-2-amino-1,3,4-thiadiazole, 5~cyclohexyl-2-amino-
1~3,4-thiadiazole, 5-cycloheptyl-2-amino-1,3,4-thiadiazole and
the like.
~0~95ZZ
The acetal of formula VII when not readily available
can be prepared by reacting an amine of the formula
- N - H
12 (IX)
wherein R2 is as heretofore described with the dimethyl or
diethyl acetal of~ -bromopropionaldehyde. This reaction can
be effected by combining from about 1 to about 2 molar amounts
of the amine of formula IX with one molar amount of the acetal
of ~-bromopropionaldehyde in about equimolar proportions in
an inert organic reaction medium such as methanol. The reaction
mixture can then be heated at reflux for a period of from about
4 to about 8 hours. After this time the reaction mixture can
be cooled to room temperature and an alkali metal hydroxide
or carbonate can be added in an amount sufficient to neutralize
the reaction mixture. Stirring can be continued at room tem-
perature for a period of up to about 24 hours to ensure comple-
tion of the reaction. After this time the reaction mixture
can be filtered and the filtrate distllled under reduced pressure
to yield the desired product.
Exemplary compounds cf formula IX are methylamine,
ethylaminey propylamine, isopropylamine, n-butylamine, t-butyl-
amine, pentylamine, hexylamine, allylamine, proparagylamine,
2-butenylamine, 3-butenylamine, 3-pentenylamine, 4-pentenylamine,
5-hexenylamine, 1-methyl-2-propynylamine, 1,l_dimethyl-2-propynyl-
amine, 1-ethyl-2-propynylamine, 1,1-diethyl-2-propynylamine,
l_propyl-2-propynylamine, 1,1-dipropyl-2-propynylamine, 1-
chloroàllylamine, l-bromoallylamine, 4-chloro-2-butenylamine,
6-chloro-4-hexenylamine and the like.
Exemplary suitable acid anhydrides of formula III are
acetic anhydride, propionic anhydride, butanoic anhydride,
pentanoic anhydride, hexanoic anhydride, acrylic anhydride,
butenoic anhydride, pentenoic anhydride, chloroacetic anhydride,
495Z~2
bromo~cetic anhydrid~ chlorobutanoic anhydride, cyclohexyl
carboxylic anhydride, benzoic anhydride, toluic anhydride, 4-
chloroben~oic anhydride, 3-bromobenzoic anhydride, ~-~luorobenzoic
anhydride, 4-methoxybenzoic anhydride, 4-ethoxybenzoic anhydride,
4-chloromethylbenzoic anhydride, 4-trifluoromethylbenzoic anhy-
dride, 3,4,5-trichlorobenzoic anhydride, phenylacetic anhydride, ~ -
4-methylphenylacetic anhydride, ~-phenylpropionic anhydride,
~-phenylbutanoic anhydride, propynoic anhydride, butynoic anhy-
dride, methoxyacetic anhydride, ~-methoxypropionic anhydride,
~-ethoxybutanoic anhydride and the like.
Exemplary suitable acid chlorides o~ formula IV
useful for preparing the compounds of the present invention
are the acid halides of the same acids as set forth above
in the examples of acid anhydrides. '
The manner in which the compounds of the present
invention can be prepared is more specifically illustrated ,~
in the ~ollowing examples.
E~ple 1
Preparation of 5-Methyl-
1,3,4-thiadiazol-2-yl ~socyanate Dimer
A saturated solution of phosgene in ethyl acetate
tlOOml) is charged into a glass reaction vessel equipped with
a mechanical stirrer. A slurry of 5-methyl_2-amino-1,3,4-
thiadiazole (40grams) in ethyl acetate (300ml) is added to
the reaction vessel and the resulting mixture is s~irred for
a period of about 16 hours, resulting in the formation of a
precipitate. The reaction mixture is then purged with nitrogen
gas to remove unreacted phosgene. Ths purged mixture is then
filtered to recover the precipitate. The precipitate is then
recrystallized to yield the desired product 5-methyl-1,3,4-
thiadiazol~2-yl isocyanate dimer.
- 8
5Z~i'
Example _
Preparation of the Dimethyl Acetal
of 3-Methylaminopro~ionaldehyde
Methylamine (1.0 mole), the dimethyl acetal of 3-
bromopropionaldehyde (0.5 mole) and methanol (100 ml) are charged
into a glass reaction vessel equipped with a mechanical stirrer,
thermometer and reflux condenser. The reaction mixture is heated
at reflux, with stirring, for a period of about 4 hours. After
this time the reaction mixture is cooled to room temperature
and sodium hydroxide (20 grams) is added. The reaction mixture
is then stirred for an additional period of about 8 hours. The
reaction mixture is then filtered and the filtrate is distilled
under reduced pressure to yield the desired product the dimethyl
acetal of 3-methylaminopropionaldehyde.
Example 3
Preparation of the Dimethyl Acetal of 3-~1-Methyl_
3-(5-methyL~1,3,4-thiadiazol-2-yl)ureido~propionaldehyde
A mixture of 5-methyl-1,3'~4~hiadiazol-2-yl isocyanate
dimer tO.05 mole), the dimethyl aceta:L of 3-methylaminopropion-
aldehyde (0.1 mole) and benzene (60 mL) are charged into a glass
reaction vessel equipped with a mechanical stirrer and reflux
condenser. The reaction mixture is heated at reflux for a period
of about 15 minutes. After this time the mixture is stripped
of benzene under reduced pressure to yiedl a solid product as
the residue. The residue is then rec~ystallized to yield the
desîred product the dimethyl acetal of 3-~1-methyl-3-(5-methyl-
1,3,4-thiadiazol-2-yl)ureido~ propionaldehyde. ~ i
Example 4
Preparation of Tetrahydr~-1-(5-methyl-1,3,4-
thiadiaxol-2-yl)-3-methyl-6-hydroxy-2~1H ? -pyrimidinone
.:
The dimethyl acetal of 3-~1-methyl-3-(5-methyl-1,3,4-
thiadiazol-2-yl)ureido~propionaldehyde (15 grams), water (400 ml)
and hydrochloric acid (4 ml) are charged into a glass reaction
vessel equipped wi-th a mechanical stirrer, thermometer and reflux
',: ' ::
, . . .:
~ ~.. 04952Z
condenser. The reac-tion mixture is heated at reflux for a period
of about 15 minutes. The reaction mixture is then filtered
while hot and the filtrate i5 cooled to form a precipitate.
The precipitate is recovered by filtration, i~ dried and is
recrystallized to yield the desired product tetrahydro-1-(5-
methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6_hydroxy-2(lH)-pyrimi-
dinone.
Example 5
Preparation of Tetrahydro-1-(5-methyl-1,3,4-
thiadiazol- ?-Yl)- 3 methyl-6-acetyloxy- ~ idinone
Tetrahydro-l-(S-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-
6-hydroxy-2(1H)-pyrimidinone (0.1 mole), ace-tic anhydride (0.11
, mole), toluenesulfonic acid (0.05 gram) and benzens (100 ml)
are charg~d into a glass reaction vessel equipped wi-th a mechani- -
cal stirrer and thermometer. The reaction mixture is heated
. .
on a steam bath with stirring for a period of about 2 hours.
After this time the reaction mixture is cooled to room tempera-
ture and isstripped o~ solvent under reduced pressure leaving
a residue. The residue is recrystallized to yield the desired
~,20 product tetrahydro-1-(5-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-
6-acetyloxy~2(lH)-pyrimidinone.
Example 6
` Preparation of S-Methoxy-1,3,4-
thiadiazol-2-yl Isocyanate Dimer
~` A saturated solution of phosgene in ethyl acetate
(100 ml) is charged into a glass reaction vessel equipped with
` a mechanical stirrer. A slurry of 5-methoxy-2-amino-1,3,4-
;~ thiadiazole t40 grams) in ethyl acetate (300 ml) is added to
, :
the reaction vessel and the resulting mixture is s*irred for
~30 a period of abou-t 16 hours~ resulting in the formation of a
,' precipitate. The reaction mixture is then purged with nitrogen
,` gas to remove unreacted phosgene. The purged mixture is then
~' filtered to recover the precipitate. The precipitate is -then
~,
' ~ 10 - .
' :
.' .
.. . , ~ , ::
1049~D2Z
recrystallized to yield the desired produc-t 5-methoxy-1,3,4-
~!; thiadiazol-2-yl isocyanate dimer-.
. Exam~le 7
~ Preparation of the Dimethyl Ace-tal
- of 3-Eth~aminopropionaldehyde
Ethylamine (2.0 mole), the dimethyl acetal of 3-bromo-
propionaldehyde tl.0 mole) and methanol (100 ml) are charged
into a glass reaction vessel equipped with a mechanical stirrer,
~ thermometer and reflux condenser. The reaction mixture is heated
10 at reflux, with stirring, for a period of about 5 hours. After
this time the reaction mixture is cooled to room temperature
and sodium hydroxide (20 grams) is added. The reaction mixture
is then stirred for an additional period of about 12 hours. The
s~ reaction mixture is then filtered and the filtrate is distilled
under reduced pressure to yield the desired product the dimethyl
acetal of 3-ethylaminopropionaldehyde.
` Example~8
Preparation of the Dimethyl Acetal of 3~ (Et~yl-
3-(5-methoxy-1~3,4-thiadiaæol-2-yl3ureido~propionaldehyde
A mixture of 5-methoxy-1,3,4-thiadiazol-2-yl isocyanate
` dimer (0.05 mole), the dimethyl acetal of 3-ethylaminopropion-
.
aldehyde (0.1 moYle) and benzene (60 ml) are charged into a glass
reaction vessel equipped with a mechanical stirrer and reflux
condenser. The reaction mixture is heated at reflux for a period
:;.,.
of about 15 minutes. After t~is ~ime the mixture is stripped
i of benzene under reduced pressure to yield a solid product as
.~;
the residue. The residue is then recrystallized to yield the
.; .
desired product the dimethyl acetal of 3-Ll-ethyl-3-(5-methoxy-
7 3,4-thiadiazol-2-yl)ureido~propionaldehyde.
E_ample 9
. " . Preparation of Tetrahydro-1-(5-methoxy-1,3,4-
thiadiazol-2-yl)-3-ethyl-6-hydroxy-2(lH)~y imidinone
~; The dimethyl acetal of 3-Cl-ethyl-3-~5-methoxy-1,3,4-
!,'.':
thiadiazol-2-yl)ureido~propionaldehyde (15 grams), water (400 ml)
,`
.':
.,
.. . . . .
, ., : , :: . . ~ ... :
.
104~SZZ
and hydrochloric acid (4 ml) are charged into a glass reaction
vessel equipped with a mechanical stirrer, thermometer and reflux
condenser. The reaction mixture is heated at reflux for a period
of about 15 minutes. The reaction mixture is then filtered while
hot and the filtrate is cooled to form a precipitate. The pre-
cipitate is recovered by filtration, is dried and is recrystal-
lized to yield the desired product tetrahydro-1-(5-methoxy-1,3,4-
thiadiazol-2-yl~-3-ethyl-6-hydroxy-2(lH)-pyrimidinone.
`. ~ : ''
Preparation of Tetrahydro-1-(5-methoxy-1,3,4-
;- thiadiazol-2-yl)-3-eth~l-6-propionyloxy-2~lH)-pyrimidinone
Tetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-
.:,
6-hydroxy-2(1H)-pyrimidinone (0.1 mole), propionic anhydride
; (0.11 mole), to~uenesulfonic acid (0.05 gr-am) and benzene (100 ml)
are charged into a glass reaction vessel equipped with a mechani-
cal stirrer and thermometer. The reaction mixture is heated on
.:,
a steam bath with stirring for a period of about 2 hours. After
this time the reaction mixture is cooled to room temperature
r" and is stripped of solvent under reduced pressure leaving a
,~ 20 residue. The residue is recrystallized to yield the desired
product tetrahydro-l-tS-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-
6-propionyloxy-2(lH)-pyrimidinone.
Example 11
,~., !
~, Preparation of 5-Methylthio-
3 ? 4-thiadiazol-2-yl Isoc~anate Dimer
. .. .
A saturated solution of phosgene in ethylacetate
tlOO ml) is charged into a glass reaction vessel equipped with
.,.j ~,
a mechanical stirrer. A slurry of 5-methylthio-2-amino-1,-3,4-
thiadiazole t~45 grams) in ethyl acetate t300 ml) is added to
the reaction vessel and the resulting mixture is stirred for a
period of about 16 hours, resulting in the formation of a pre-
cipitate. The reaction mixture is then purged with nitrogen
gas to remove unreacted phosgene. The purged mixture is then
- 12 -
j:, .
, ~
.. . . .
, . , ' ' . ' .; '
: i - . . - . , ~
.. ~ , .
~349S~Z
filtered to recover the precipitate. The precipitate is then
recrystallized to yield the desired product 5-methylthio-1,3,4-
thiadiazol-2-yl isocyana-te dimer.
Example 12
Preparation of the Dimethyl Acetal
of 3-Propylaminopropionaldehyde
Propylamine ~2.0 mole), the dimethyl acetal of 3-
bromopropionaldehyde (1.0 mole) and methanol (100 ml) are charged
into a glass react1~on vessel equipped with a mechanical stirrer,
thermometer and reflux condenser. The reaction mixture is
heated at reflux~ with stirring, for a period of about 3 hours.
After this time the reaction mixture is cooled to room tempera-
ture and sodium hydroxide t20 grams) is added. The reaction
mixture is then stirred for an additional period of about 6
hours. The reaction mixture is then filtered and the filtrate
is distilled under reduced pressure to yield the desired product
",
~ the dimethyl acetal of 3-propylaminopropionaldehyde.
".
- Example 13
Preparation of the Dimethyl Acetal of 3- ~-Propyl-3-
(5-methylthio~ ,4-thiadiazol-2-yl)ureido~ropionaldehyde
A mixture of 5-methylthio-1,3,4-thiadiazol-2-yl iso-
cyanate dimer (0.05 mol~), the dimethyl acetal of 3-propylamino-
; propionaldehyde (0.1 mole) and benzene (60 ml) are charged into
a glass reaction ~essel equipped with a mechanical stirrer and
reflux condenser. The reaction mixture is heated at reflux for
;~ a period of about 15 minutes. After this time the mixture is -
~ stripped of benzene under reduced pressure to yield a solid
i; ~ :
product as the residue. The residue is then recrystallized
to yield the desired product the dimethyl acetal of 3-Cl-propyl- -~
30 3-(5-methylthio-1,3,4-thiadiazol-2-yl)ure~do~propionaldehyde.
' ! Example 14~-
Preparation of Tetrahydro-1-(5-methylthio-1,3,4-
; thiadiazol-2-yl)-3-pro~yl-6-hydroxy-2(lH)-pyrimidinone
;~: :'
The dimethyl acetal of 3-~1-propyl-3-(5-methylthio-
.:~
, ' ~ :.
" . . .
~9szz
1,3,4-thiadiazol-2-yl)ureido propionaldehyde (15 grams), water
(400 ml) and hydrochloric acid (4 ml) are charged into a glass
reaction vessel equipped with a mechanical stirrer 7 thermometer
and reflux condenser. The reaction mixture is heated at reflux
for a period of about 15 minutes. The reaction mixture is then
filtered while hot and the filtrate is cooled to form a precipi-
tate. The precipitate is recovered by filtration, is dried and
is recrystallized to yield the desired product tetrahydro-l-
~ t5-methylthio-1,3,4-thiadiazol-2-yl)-3-propyl-6-hydroxy-2(1H)-
pyrimidinone.
Exam~le 15 ~-
.
Preparation of Tetrahydro-l-tS-methylthio-1,3,4-
thiadiazol-2-yl)-3-propyl-6-butanoyl~y-2 (lH)-pyrimidinone
Tetrahydro-1-(5-methylthio-1,3,4-thiadiazol-2-yl)-
3-propyl-6-hydroxy-2(1H)-pyrimidinone (0.1 mole), butanoic
`~ anhydride (0.11 mole), toluenesulfonic acid (0.05 gram)Oand
benzene (100 ml) are charged into a glass reaction vessel
- equipped with a mechanical stirrer and thermometer. The reaction
mixture is heated on a steam bath with stirring for a period
~ 20 of about 2 hours. After this time the reaction mixture is cooled
,~ to room temperature and is stripped of solvent under reduced
pressure lea~ing a residue. The residue is recrystall~;zed to
i~.` yield the desired product tetrahydro-l-(5-methylthio-1,3,4-
thiadiazol-2-yl)-3-propyl-6-butanoyloxy-2tlH)-pyrimidinone.
Example 16
Preparation of 5-Methylsulfonyl-
1,3,4-~thiadiazol-2-yl Isocyanate Dimer
A saturated solution of phosgene in ethyl acetate
:
`~, (100 ml) is charged into a glass reaction vessel equipped with
a mechanical stirrer. A slurry of 5 methylsu~fonyl-2-amino-
1,3,4-thiadiazole (50 grams) in ethyl acetate (300 ml) is added
to the reaction vessel and the resulting mixture is stirred for
a period of about 16 hours, resulting in the formation of a
- 14
.~
''~' .
~ ~495ZZ
precipitate. The reaction mixt~re is then purged with nitrogen
gas to remove unreacted pho~gene. The purged mixture ls then
filtered to recover the precipitate. The precipitat~ is then
recrystallized to yield the desired product 5-methylsulfonyl-
1,3,4-thiadiazol~2-yl isoeyanate dimer.
Example 17
Preparation of the Dimethyl Acetal
of 3~Allylamino~ropionaldehyde
Allylamine (1.0 mole), the dimethyl acetal of 3 bromo-
propionaldehyde (O.S mole) and methanol (lOO ml) are charged
into a glass reaction vessel equipped with a mechanical stirrer,
thermometer and reflux condenser. The reaction mixture is
heated at reflux, with stirring, for a period of about 8 hours.
After this time the reaction mixture is cooled to room tempera-
ture and sodium hydroxide (20 grams) is added. The reaction
mixture is then stirred for an additional period of about 14
hours. The reaction mixture is then filtered and the filtrate
is distilled under reduced pressure to yield the desired product
the dimethyl acetal of 3-allylaminopripionaldehyde.
Examp~e 18
Preparation of the Dimethyl Acetal of 3-~l-Allyl-3-(5-
methylsulf~yl-1~3~4-thiadiazol-2-yl)ureido~propionaldehyde
A mixture of 5-methylsulfonyl-1,3,4-thiadiazol-2-yl
isocyanate dimer (0.05 mole), the dimethyl acetal of 3-allylamino-
propionaldehyde (0.1 mole) and benzene (60 ml) are charged into
a glass reaction vessel equipped with a mechanical stirrer and
reflux condenser. The reaction mixture is heated at reflux for
a period of about 15 minutes. After this time the mixture is
stripped of benzene under reduced pressure to yield a solid - ~
30 product as the residue. The residue is then recrystallized ~ ~ -
to yield the desired product the dimethyl acetal of 3-El-allYl~
3-tS-methylsulfonyl-1,3,4-thiadiazol-2 yl)ureido]propionaldehyde.
.
~ - 15
.
~95ZZ
Example 19
Preparation of Tetrahydro-1-(5-methylsulfonyl-1,3,4-
thiadiazol-2-yl)-3-allyl-6-hydroxy-2(lH)-pyrimidinone
The dimethyl acetal of 3-~1-methyl-3-(5-methylsulfonyl-
1,3,4-thiadiazol-2-yl)ureido~ propionaldehyde (15 grams), water
(400 ml) and hydrochloric acid (4 ml) are charged into a glass
reaction vessel equipped with a mechanical stirrer, thermometer
and reflux condenser. The reaction mixture is heated at reflux
for a period of about 15 minutes. The reaction is then filtered
while hot and the filtrate is cooled to form a precipitate.
The precipitate is recovered by filtration, i3 dried and is
recrystallized to yield the desired product tetrahydro-l-(5-
methylsulfonyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-hydroxy-2(1H)-
pyrimidinone.
Example 20
Preparation of Tetrahydro-l-
(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-
3-allyl-6-cyclohexylcarbonyloxy-2(lH)-pyrimidinone
Tetrahydro-1-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-
- 20 3-allyl-6-hydroxy-2(1H)-pyrimidinone (0.1 mole), cyclohexane
carboxylic anhydride (0.11 mole), toluenesulfonic acid (0.05
gram) and benzene (100 ml) are charged into a glass reaction
vessel equipped with a mechanical stirrer and thermometer. The
reaction mixture is heated on asteam bath with stirrin~ for
a period of about 2 hours. After this time the reaction m~xture
is cooled to room temperature and is stripped of solvent under
reduced pressure leaving a residue. The residue is recrystallized
to yield the desired product tetrahydro-l-(5-methylsulfonyl-
1,3,4-thiadiazol-2-yl)-3-allyl-6-cyclohexylcarbonyloxy-2(1H)-
pyrimidinone.
ExamRle 21
Preparation of 5-Cyclopropyl-
- 153,4-thiadiazol-2-yl Isocyanate Dimer
A saturated solution of phosgene in ethyl acetate
- 16
~'
~o~s~
(100 ml) i5 charged into a glass reaction yessel equipped with
a mechanical stirrer. A slurry of 5-cyclopropyl-2-amino-1,3,4-
thiadiazole (50 grams) in ethyl acetate (300 ml) is added to t
the reaction vessel and the resulting mixture is stirred Por
a period of about 16 hours, resulting in the forma~ion of a
precipitate. The reaction mixture is then purged with nitrogen
gas to remove unreacted phosgene. The purged mixture is then
filtered to recover the precipitate. The precipitate is then
recrystallized to yield the desired product 5-cyclopropyl-1,3,~-
10 thiadiazol_2-yl isocyanate dimer.
Example 22
Preparation of the Dimethyl Acetal
of 3-Propargylaminopropionaldehyde
Proparg~lamine (2.0 mole), the dimethyl acetal of ;~
3-bromopràpionaldehyde (1.0 mole) and methanol (100 ml) are
charged nnto a glass reaction vessel equipped withd mechanical
stirrer, thermometer and reflux condenser. The reaction mixture
is heated at reflux, with stirring, for a period of about 6
hours. After t~is time the reaction mixture is cooled to room
20 temperature and sodium hydroxide (20 grams) is added. The -
reaction mixture is then s~rred for an additional period of
about 18 hours. The reaction mixture is then filtered and the
filtrate is distilled under reduced pressure to yield the desired
product the dimethyl acetal of 3-propargylaminopropionaldehyde.
Example 23
Preparation of the Dimethyl Acetal
of 3~ Propargyl-3-(5-cyclopropyl-
1?3,4-thiadiazol-2-~l)ureidolpropionaldehyde
A mixture of 5-cyclopropyl-1,3,4-thiadiazol-2-yl iso-
30 cyanate dimer (0.05 mole), the dimethyl acetal of 3-propargyl-
aminopropionaldehyde (0.1 mole) and benzene (60 ml) are charged
into a glass reaction vessel equipped with a mechanical stirrer
and reflux condenser. The reaction mixture is heat-ed at reflux
for a period of about 15 minutes. After this time the mixture
~1~45~5Zz
is stripped of benzene under reduced pressure to yield a solid
product as the residue. The residue is then recrystallized to
yield the desired product the dimethyl acetal of 3-~1-propargyl-
3-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)ureido~propionaldehyde.
Example 24
Preparation of Tetrahydro-1-(5-cyclopropyl_1,3,4-
thiadiazol-2-yl)-3-propargyl-6-hydroxy-2(lH)-pyrimidinone
The dimethyl acetal of 3~ propargyl-3-(5-cyclopropyl-
1,3,4-thiadiazol-2-yl)ureido~propionaldehyde (15 grms), water
(400 ml) and hydrochloric acid (4 ml) are charged into a glass
reaction vessel equipped witha mechanical stirrer, thermometer
and reflux condenser. The reaction mixture is heated at reflux
for a period of about 15 minutes. The reaction mixture is then
filtered while hot and the filtrate is cooled to form a precipi-
tate. The precipitate is recovered by filtration, is dried and
is recrystallized to yield the desired product tetrahydro-1-
(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-3~propargyl-6-hydroxy-
2(1H)-pyrimidinone.
Example 25 ~ ~
Preparation of Tetrahydro-1-{5-cyclopropyl-1,3,4- -
; thiadiazol-2-yl)-3-~ropargyl-6-benzoyloxy-2(1H)-~rimidinone
Tetrahydro-1-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-
; 3-propargyl-6-hydroxy-2(1H)-pyrimidinone (0.1 mole), benzoic
~` anhydride (0.11 mole), toluenesulfonic acid~0.05 gram) and
benzene (100 ml) are charged into a glass reaction vessel
equipped witha!mechanical stirrer and thermometer. The reaction
mixture is heated on a steam bath with stirring for a period
of about 2 hours. After this time the reaction mixture is cooled
to room temper~ture and is stripped of solvent under reduced
pressure leaving a residue. The residue is recrystallized to
yield the desired product tetrahydro-1-(5-cyclopropyl-1,3,4-
thiadiazol-2-yl)-3-propargyl-6-benzoyloxy-2(lH)-pyrimidinone.
'
-~ - 18 -
.,
...... . . . ....... ..
.,.~....
~(~451i5Z2
_ample 26
Preparation of 5-Trifluoromethyl-
1,3,4-thiadiazol-2-yl Isocyanate Dimer
A saturated solution of phosgene in ethyl acetate
(100 ml) was charged into a glass reaction vessel equipped with
a mechanical stirrer. A slurry of 5-trifluoromethyl-2-amino-
1,3,4-thiadiazole (45 grams) in ethyl acetate (300 ml) was added
to the reaction vessel and the resulting mixture was stirred
for a period of about 16 hours resulting in the formation of
a precipitate. The reaction mixture was then purged with nitrogen
gas to removP unreacted phosgene. The purged mixture was filtered
` to recover 48 grams of a white solid. This sol4d was recrystal-
lized from dimethyl fo~mamide to yield the desired product 5- ~ -
trifluoromethyl-1,3,4-thiadiazol-2-yl isocyanate dimer.
Example 27
Preparation of the Dimethyl Acetal
of 3~ Methyl-3-(5-trifluoromethyl-
' 1,3,4~thiadiazol-?-yl)ureido~pro ~ naldehyde :
A mixture of 5-trifluoromethyl-1,3,4-thiadiazol 2-yl
isocyanate dimer (9.5 grams), the dimethyl acetal of 3-methyl-
aminopropionaldehyde (5.8 grams) and benzene (60 ml) are charged
into a glass reaction vessel equipped with a mechanical stirrer
and reflux condenser. The reaction mixture is heated at reflux
for a period of about 15 minutes. After this time the mixture
is stripped of benzene under reduced pressure to~yield a colid
product as the residue. This product is recrystaliized to yield
the desired product the dimethyl acetal of 3~ methyl-3-(S-
trifluoromethyl-1,3,4-thiadiazol-2-yl)ureido~propionaldehyde.
Example 28
Preparation of Tetrahydro-1-(5-trifluoromethyl-1,3,4-
thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone
The dimethyl acetal of 3-~1-methyl-3-(5-trifluoromethyl-
. 1,3,4-thiadiazol-2-yl)ureidolpropionaldehyde (15 grams), water
(400 ml) and hydrochloric acid (4 ml) are charged into a glass
:'! -- 19
. ' '. . . ' , ', ' : . , . ' . ' ' '': .,.'.
:, . ' ~ . . . . . .
,,
495Z~
reaction vessel equipped with a mechanical stirrer, thermometer
and reflux condenser. The reaction mixture is heated at reflux
for a period of about 15 minutes. The reaction mixture is then
filtered while hot and the filtrate is cooled resulting in the
formation of a precipitate. The precipitate is recovered by
filtration, is dried and îs recrystallized to yield the desired
product tetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-
3-methyl-6-hydroxy-2(lH)-pyrimidinone.
_ample 29
Preparation of Tetrahydro-l (5-trifluoromethyl-1,3,4-
thiadiazol-2-yl)-3-methyl-6-acetyloxy-2(lH)-pyrimidinone
Tetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)- --~
3-methyl-6-hydroxy-2(1H)-pyr~midinone (0.1 mole), acetic anhydride
; (0.11 mole), toluenesulfonic acid (0.05 gr~m~ and~-benzene (~lQOsml)
are charged into a glass reaction vessel equipped with a mechani-
cal stirrer and thermometer. The reaction mixture is heated
on a steam bath with stirring for a period of about 2 hours.
After this time the reaction mixture is cooled to room -tempera-
ture and is stripped of solvent under reduced pressure leaving
a residue. The residue is recrystallized to yield the desired
product tetrahydro-l-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-
3-methyl-6-acetyloxy-2(1H)-pyrimidinone.
Example 30 ;~
Preparation of 5-t-Butyl-
1,3,4-thiadiazol-2-yl Isocyanate Dimer
A saturated solution of phosgene in ethyl acetate
(100 ml) was charged into a glass reaction vessel equipped with
a mechanical stirrer. A slurry of 5-t-butyl-2-amino-1,3,4-
thiadia~ole (10 grams) in ethyl acetate (300 ml) was added to
the reaction vessel and the resulting mixture was stirred for
a period o~ about 16 hours resulting in the formation of a pre-
cipitate. The reaction mixture was then purged with nitrogen
gas to remove unreacted phosgene. The purged mixture was then
.'
- 20
---`` ~!L(~495,~2
filtered to recover the desired product S-t-butyl-1,3,4-thiadiazol-
2-yl isocyanate dimer as a solld having a melting point of 261
to 263C.
Example 31
Preparation of the Dimethyl Acetal of 3-1-Methyl-3-
(5-t-butyl-1,3~4-thiadiazol-2-yl)ureido~propionaldehyde
A mixture of 5-t-butyl-1,3,4-thiadiazol-2-yl isocyanate
" dimer (6 grams), the dimethyl acetal of 3-methylaminopropion-
; aldehyde (4.0 ~rams) and benzene (S0 ml) are charged into a glass
reaction flask equipped with a mechanical stirrer and reflux
condenser. The reaction mixture is heated at reflux, with
stirring, for a period of about 5 minutes. After this time the
; reaction mixture is stripped of benzene to yield a residue.
The residue is then recrystalliæed to yield the desired product
the dimethyl acetal of 3-¦1-methyl-3-(5-_-butyl-1,3,4-thiadiazol-
2-yl)ureido~propionaldehyde.
` Ex_mple 32
` Preparation of Tetrahydro-1-(5-t-butyl-1,3,4-
thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone
The dimethyl acetal of 3-~1-methyl-3-(5-t-butyl-
:~ .
1,3,4-thiadiazol-2-yl)ureido~propionaldehyde (16 grams), con- - ~
~. ,
- centrated hydrochloric ~cid (10 ml) and water t500 ml~ are
charged into a glass reaction vessel e~uipped with a mechanical
stirrer, thermometer and reflux condenser. The reaction mixture
is filtered while hot and the filtrate is then cooled, resulting
. ~ , .
in the formation of a precipitate. The precipitate is recovered
by filtration, dried and is recrystallized to yield and the desired
product tetrahydro-l-t5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-
6-hydroxy-2(lH)-pyrimidinone.
Example 33 `
~ Preparation of Tetrahydro-1-(5-t-butyl'1,3,4-
; thiadiazol-2-yl)-3-methyl-6-acetyloxy-2(lH)-pyrimidinone
Tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-
6-hydroxy-2(1H)-pyrimidinone (0.1 mole), acetic anhydride (0.11
.
- 21
.
.,. ~
"
r-~
1~4~5'~'~
mole), toluenesulfonic acid (0.05 gram) and benzene (100 ml)
are charged into a glass reaction vessel equipped with a mechani-
-- cal stirrer and thermometer. The reaction mix-ture is heated
on a steam bath with stirring for a period of about 2 hours.
After this time the reaction mixture is cooled to room tempera-
ture and is ~tripped of solvent under reduced pressure leaving
,; a residue. The residue is recrystallized to yield the desired
product tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-
6-acetyloxy-2(lH)-pyrimidinone.
Example 34
Preparation of Tetrahydro-l-
(5-tri~luoromethyl-1,3,4-thiadiazol-2-yl)-
; 3-methyl-6-benzoyloxy-?~lH)-Pyrimidinone
Tetrahydro l-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl~
3-methyl-6-hydroxy-2(lH)-pyrimidinone (0.05 mole), triethylamine
(0.06 mole) and 'benzene (50 ml) are charged into a glass reaction
vessel equipped with amechanical stirrer, thermometer and reflux
condenser. Benzoyl chloride (0.05 mole) is then added dropwise -
with stirring. After the addition is completed, the reaction
mi~ture is heated at reflux with continued stirring for a period
of about 30 minutes. A~ter this time the reaction mixture is
filtered and the filtrate is stripped of solvent under reduced
' pressure to yield a solid residue. The residue is recrystallized
to yield the desired product tetrahydro-1-(5-trifluoromethyl-
1,3,4-thiadiazol-2-yl)-3-methyl-6-benzoyloxy-2(lH)-pyrimidinone.
Example 35
^ Pr~paration of Tetrahydro-l!'
(S-~-butyl-1,3,4-thi~ad~azol-2-yl)
3-methyl-6-benzoyloxy-2(lH)-~yrimidinone
Tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol_2_yl)-3-methyl-
i 6-hydroxy-2(lH)-pyrimidinone (0.05 mole), triethylamine (0.06
mole~ and benzene (50 ml) are charged into a glass reaction
.
vessel equipped withalmechanical stirrer, thermometer and reflux
condenxer. Benzoyl chloride (0.05 mole) is then added dropwise
.',
_ 22 -
:' -
5Z;Z
with stirring. After the addition is completed, the reaction
mixture is heated at reflux with continued stirring for a period
of about 30 minutes. Af-ter this time the reaction mixture is
; filtered and the filtrate i5 stripped of solvent under reduced
pressure to yield a solid residue. The residue is recrystallized
- to yield the desired product tetrahydro-1-(5-t-butyl-1,3,4-
thiadiazol-2-yl)-3-methyl-6-benæoyloxy-2(1H)-pyrimidinone.
Additional compounds within the scope of this invention
which can be prepared by the procedures of the foregoing examples
10 are tetrahydro-1-(5-ethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-
acryloyloxy-2(lH)-pyrimidinone, ~etrahydro-1-(5-propyl-1,3,4-
thiadiazol-2-yl)-3 butyl-6-but-3-enoyloxy-2(1H)-pyrimidi~one,
tetrahydro-1-(5-butyl-1,3,4-thiadizaol-2-yl)-3-pentyl-6-pent-3-
enoyloxy-2(lH)-pyrimidinone, tetrahydro-1-(5-pentyl~ 3,4-
thiadiazol-2-yl)-3-hexyl-6-hex-4-enoyloxy-2(1H)-pyrimidinone,
tetrahydro-1-(5-hexyl-1,3,4-thiadiazol-2-yl)-3-pent-3-anyl-6-
pentanoyloxy-2(lH)-pyrimidinone, tetrahydro-1-(5-cyclopropyl-
1,3,4-thiadiazol-2-yl)-3-hex-4-enyl-6-hexanoyloxy-2(1H)-pyrimidin-
one, tetrahydro-1-(5-cyclobutyl-1,3,4-thiadiazol-2-yl)-3-bromo-
,c 20 methyl-6-but~noyloxy-2(1H)-pyrimidinone, tetrahydro-1-(5-cyclo-
pentyl-1,3,4-thiadiazol-2-yl)-3-trichloromethyl-6-chloroacetyloxy-
2(1H)-pyrimidinone, tetrahydro-1-(5-cyclohexyl~1,3,4-thiadiazol-
2-yl)-3-~-chlorohexyl-6-bromoacetyloxy-2(1H)-pyrimidinone,
tetrahydro-1-(5-cycloheptyl-1,~,4-thiadiazol-2-yl)-3-~-bromoethyl-
6-~-chlorobutanoyloxy-2~1H)-pyrimidinone, tetrahydro-1-(5-allyl-
1,3,4-thiadiazol-2-yl)-3-(1,1-diethylprop-2-ynyl)-6-cyclopropyl-
carbonyloxy-2(lH)-pyrimidinone, tetrahydro-1-(5-but-3-enyl_
1,3,4-thiadiazol-2-yl)-3-(1,1-dipropylprop-2-ynyl)-6-cyclobutyl-
carbonyloxy-2(1H)-pyrimidinone, tetrahydro-1-(5-pent-4-enyl-
30 1,3,4-thiadiazol-2-yl)-3-methyl-6-cyclopentylcarbonyloxy-2(1H)-
pyrimidinone, tetrahydro-1-(5-hex-4-enyl-1,3,4-thiadiazol-2-yl)-
3-methyl-6-cyclohexylacarbonyloxy-2(1H)-pyrimidinone~ tetrahydro-
. i
;`. :
. .
,''
..~
1~4~5;~:Z
1-(5-chloromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-cycloheptyl-
carbonyloxy-2(1~l)-pyrimidinone, tetrahydro-1-(5-bromome-thyl-
1,3,4-thiadiazol-2-yl)-3-methyl-6-(4-methylthiobenzoyloxy)-2(1H)
pyrimidinone, tetrahydro-1-(5-trichloromethyl-1,3,4-thiadiazol
2-yl)-3-methyl-6-(4-ethylthiobenzoyloxy)-2(lH)-pyrimidinone,
tetrahydro-1-(5-~-chloroethyl-1,394-thiadiazol-2-yl)-3-methyl-
6-(3-propylthiobenzoyloxy)-2(lH)-pyrimidinone, tetrahydro-l-
(5-~-bromoethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(3-hexylthio-
benzoyloxy)-2(lH)-pyrimidinone, tetrahydro-1-(5-~-chlorohexyl-
1,3,4-thiadiazol-2-yl)-3-methyl-6-(3,4,5-trichlorobenzoyloxy)- -~
2(lH)-pyrimidinone, tetrahydro-1-(5-ethoxy-1,3,4-thiadiazol-2-yl)- :.
3-methyl-6-(3-ethylbenzoyloxy)-2(lH)-pyrimidinone, tetrahydro-
1-(5-propoxy-1,3,4 thiadiazol-2-yl)-3-methyl-6-(4-propylbenzoyl-
oxy)-2(lH)-pyrimidinone, tetrahydro-1-(5-butoxy-1,3,4_thiadiazol-
2-yl)-3-methyl-6_(4-butylbenzoyloxy)-2(1H)-pyrimidinone, tetra-
hydro-1-(5-hexyloxy-1,3,4-thiadiazol-2-yl)-3-methyl-6-(4-hexyl-
- benzoyloxy)-2(lH)-pyrimidinone, tetrahydro-1-(5-ethylthio-1,3,4-
thiadiazol-2-yl)-3-methyl-6-(4-bromobenzoyloxy-~ 2~lH)-pyrimidin-
one, tetrahydro-1-(5-propylthio-1,3,4-thiadiazol-2-yl)-3-methyl-
6-(4-iodobenzoyloxy)-2(1H)-pyrimidinone, tetrahydro-1-(5-hexyl-
' thio-1,34-thiadiazol_2-yl)--3-methyl-6-(4-fluorobenzoyloxy)-
: 2(1H)-pyrimidinone, tetrahydro-1-(5-ethylsulfonyl-1,3,4-thiadiazol-
2-yl)-3-methyl-6-(2-ethoxybenzoyloxy)-2(1H)-pyrimidinone, tet~a-
hydro-1-(5 propylsulfonyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-
(3-propoxybenzoyloxy)-2(1H)-pyrimidinone, tetrahydro-1-(5-
; butylsulfonyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(4_hexyloxy-
. benzoyloxy)-2(lH)-pyrimidinone, tetrahydro-1-(5-hexylsulfonyl-
1,3,4-thiadiazol-2-yl)-3-methyl-6-(3-chloromethylbenzoyloxy)-
. 2tlH)-pyrimidinone, tetrahydro-1~(5-ethylsulfinyl-1,3,4-thiadiazol-
2-yl)-3-methyl-6-(4-trifluoromethylbenzoyloxy)-2~1M)-pyrimidinone,
tetrahydro-1-(5-propylsulfinyl-1,3,4-thiadiazol-2-yl)-3-methyl-
6-(4-~-bromoethylbenzoyloxy)-2(1H)-pyrimidinone, tetrahydro-l-
: - 24 -
95Z2
(5-hexylsulfinyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-acetyloxy-
2(lH)-pyrimidinone, tetrahydro-l-(5-trifluoromethyl-1,3,4-
thiadiazol-2-yl)-3-methyl-6-bromoacetyloxy-2(lH)-pyrimidinone,
tetrahydro-1-(5-trifluoromethyl-1,3,4--thiadiazol-2-yl)-3-methyl-
6-~-chloropropanoyloxy-2(lH)-pyrimidinone, tetrahydro-l-(5-
trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-~-bromopentan-
oyloxy-2(lH)-pyrimidinone, tetrahydro-1-(5-trifluoromethyl- -
1,3,4-thiadiazol-2-yl)-3-methyl-6-~-chlorohexanoyloxy-2(1H)-
pyrimidinone, tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-
10 3-methyl-6-but-3-enoyloxy-2(1H)-pyrimidinone, tetrahydro-l-
(5-~-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-pent-4-enoyloxy-
2(lH)-pyrimidinone, tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-
2-yl)-3-methyl-6-hex-4-enoyloxy-2(1H)-pyrimidinone, tetrahydro-
1-(5-t butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-but-3-ynyloxy-
2(lH)-pyrimidinone, tetrahydro-l-(5-_-butyl-1,3,4-thiadiazol-
2-yl)-3-methyl-6-hex-4-ynoyloxy-2(1H)-pyrimidinone and the like.
For practical use as herbicides the compounds of this
invention are generally incorporated.iinto herbicidal compositions
which comprise an inert carrier and a herbicidally to~ic amount
~0 of such a compound. Such herbicidal compositions, which can
also be called formulations, enable the active compound to be
applied conveniently to the site of the weed infestation in
any desired quantity. These compositions can be solids such
as dusts, granules, or wettable powders; or they can be liquids
such as solutions, aerosols, or emulsifiable concentrates.
For example, dusts can be prepared by grinding and
blening the active compound with a soltd inert carrier such
as the talcs, clays, silicas, pyrophyllite, and the like. Granu-
lar formulations can be prepared by impregnating the compound,
usually dissolved in a suitable solvent, onto and into granulated
carriers such as the attapulgit~s or the vermiculitss, usually
of a particle size range of from about 0.3 to 1.5 mm. Wettable
powders, which can be dispersed in water or oil to any desired
~ ..
_ 25
~0~5~52Z
concentration of the active compound, can be prepared by incorpor-
ating wetting agents into concentrated dust compositions.
In some cases the active compounds are sufficiently
soluble in common organic solvents such as kerosene or xylene
so that they can be used directly as solu-tions in these solvents.
Frequently, solutions of herbicides can be dispersed under super-
atmospheric pressure as aerosols. However, preferred liquid
herbicidal compositions are emulsifiab],e concentrated, which
comprise an,~active compound according to this invention and
~ 10 as the inert carrier, a solvent and an emulsifier. Such emulsifi-
'~ able concentra-tes can be extended with water and/or oil to any
` desired concentra-tion of active compound for application as
sprays to the site of the weed infestation. The emulsifiers
~ most commonly used in these concentrate~ are nonionic or mixtures
', of nonionic with anionic surface-active agents. With the use
of some emulsifier systems an inverted emulsion (water in oil)
~' can be prepared for direct application to weed infestations.
' A typical herbicidal composition accordi~g to th~s
invention is illustrated by the following example, in which
20 the quantities are in parts by weight.
Example 36
Preparation of a Dust
', Product of Example 5 10
Powdered Talcc 90
The above ingredients are mixed in a mechanical
' grinder-blender and are ground until a homogeneous, free-flowing
dust of the desired particle size is obtained. This dust is
suitable for direct application to the site of -the weed infesta-
tion .
The compounds of this invention can be applied as
' herbicides in any manner recognized by the art. One method
~or the control o~ weeds comprises contacting the locus of said
.;.
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~049~Z2
weeds with a herbicidal composition comprising an inert carrier
and as an essential active ingredient, in a quantity which is
herbicidally toxic to said weeds, a compound o~ the present
invention. The concentration of the new compounds of this inven-
tion in the herbicidal compositions will vary greatly with the
type of formulation and the purpose ~or which it is designed,
but generally the herbicidal compositions will comprise from
about 0.05 to about 95 percent by weight of the active compounds
of this invention. In a preferred embodiment of this invention,
the herbicidal co~positions will comprise from about 5 to about
; 75 percent by weight o~ the active compound. The compositions
can also comprise such additional substances as other ~esticides,
such as insecticides, nematocides, fungicides, and the like;
stabilizers, spreaders, deactivators, adhesives, stickers, ferti-
lizers, activators, synergists, and the like.
The compounds of the present invention are also useful
, ~ , ,
when combined with other herbicides andtor defoliants, dessicants,
growth inhibitors, and the like in the herbicidal compositions
heretofore described. These other materials can comprise from
~ 20 abou~ 5% to about 95% of the active ingredients in the herbicidal
; compositions. Use of combinations of these other herbicides
and/or defoliants~ dessi~ants, etc. with the compounds of the
: pres~nt invention provide herbicidal compositions which are
more effective in controlling weeds and often provide results
unattainable with separate compositions of the indvidual herbi-
cides.
Weeds are undesirable plants growing where they are -
not wanted, having no economic value, and interfering with the
production of cultivated crops, with the growing of ornamental
plants,or with the welfare of livestock. Many types of weeds
are known, including annuals such as pigw~ed, lambsquarters,
;~ foxtail, crabgrass, wild mustard, field pennycress, ryegrass,
. ~ .
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52~
goose grass, ch.ickweed, wild oats, velvetleaf, purslane,
barnyard-grass, smartweed, knotweed, cocklebur, wild buckwheat,
kochia, medic, corn cockle, ragweed, sowthistle, coffeeweed,
croton, cuphea, dodder, fumitory, groundsel, hemp nettle,
knawel, spurge, spurry, emex, jungle rice, pondweed, dog fennel,
carpetweed, morningglory, bedstraw, ducksalad, naiad, cheatgrass,
fall panicum, jimsonweed, witchgrass, switchgrass, watergrass,
: teaweed, wild turnip and sprangletop; biennials such as wild
carrot, matricaria, wild barley, campi.on, chamomile, hurdock,
mullein, roundleaved mallow, bull thistle, hounds-tongue, moth
mullein and purple star thistle; or perennials such as white
cockle, perennial ryegrass, quackgrass, Johnsongrass, Canada
thistle, hedge bindweed, Bermuda grass, sheep sorrel, curly dock,
nutgrass, field chickweed, dandelion, campanula, field bindweed,
Russian knapweed, mesquite, toadflax, yarrow, aster, gromwell,
norsetail, ironweed, sesbania, bulrush, cattail, winter-cress,
horsenettle, nutsedge, milkweed and sicklepod.
Similarly, such weeds can be classified as broadleaf
or grassy weeds. It is economically desirable to control the
growth of such weeds without damaging beneficial plants or
livestock.
The new compounds of this invention are particularly
valuable for weed control because they are toxic to many species
: and groups of weeds while they are relatively non-toxic to many
beneficial plants. The exact amount of compound required will
depend on a variety of factors, including the hardiness of the
~ particular weed species, weather, type of soil, method of
: application, the kind of beneficial plants in the same area and
the like. Thus, while the application of up to only about one or
30 two ounces of active compound per acre may be sufficient for
good control of a light infestation of weeds growing under adverse
conditions, the application of ten pounds or more of an active
i 2~
~04~3)5'~2
; compound per acre may be required for good control of a dense
infestation of hardy perennial weeds growing under favorable
conditions.
The herbicidal toxicity of the new compounds of this
invention can be illustrated by many of the established testing
techniques known to the ar-t, such as pre_ and post-emergence
testing. -
The herbicidal activity of the compounds of this
invention was demonstrated by experiments carried out for the
; 10 pre-emergence control of a variety of weeds. In these experiments
small plastic greenhouse pots filled with dry soil were seeded
with the various weed seedsO Twenty-four hours or less after
seeding the pots were sprayed with water until the soil was wet
and the test compound formulated as an aqueous emulsion of an
acetone solution containing emulsifiers was sprayed at the
indicated concentration on the surface of the soil. ~ `
After spraying, the soil containers were placed in
the greenhouse and provided with supplementary heat as required
and daily or more frequent watering. The plants were maintained
under these conditions for a period of 21 days, at which time
the condition of the plants and the degree of injury to the plants
was rated on a scale of from 0 to 10, as follows: 0 ~ no injury,
1,2 _ slight injury, 3,4 = moderate injury, 5,6 = moderately
severe in~ury, 7,8.9 - severe injury and 10 = death. The effec-
tiveness of this compound is demonstrated by the data in Table I.
The herbicidal activity of the compounds of this
invention was also demonstrated by experiments carried out for
the post-emergence control of a variety of weeds. In these
experiments the compound to be tested was formulated as an
aqueous emulsion and sprayed at the indicated dosage on the
foliage of the weeds that had attained a prescribed size. After
spraying, the plants were placed in a greenhouse and watered
, .
- 29
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~04~5ZZ
daily or more frequently. Water was not applied -to the foliage
of the -treated plants. The severity of the injury was determined
14 days after treatment and was rated on the scale of form 0
to 10 heretofore described. The effectiveness of this compound
is demonstrated by the data in Table I.
TABLE I
INJURY RATING
Product of Example 29
at 10 lbs. per acre
10 Weed SpeciesPre-emergence Post-emergence
.
Yellow Nutsedge 8 8
Wild Oats 10 10
Jimsonweed 10 10
Velvetleaf 10 --
Johnsongrass 8 10
Pigweed 7 10
Mustard 10 10
Yellow Foxtail 10 10
Barnyardgrass 10 10
20 C~abgrass 9 10
Cheatgrass 10 --
Morningglory 10 10
Bindweed -- 9
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