CA1049522A - 1-thiadiazolyl-6-acyloxytetrahydropyrimidinones - Google Patents

Abstract

Abstract of the Disclosure Disclosed are new compounds of the formula wherein R1 is selected from the group consisting of alkyl, alkenyl, haloalkyl, alkoxy, alkylthio, alkylsulfonyl, alkyl-sulfinyl and cycloalkyl; R2 is selected from the group consisting of alkyl, alkenyl, haloalkyl and wherein R4 and R5 are each selected from the group consisting of hydrogen and alkyl; and R3 is selected from the group con-sisting of hydrogen and wherein R6 is selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl and

Description

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 ~ ~ 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 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 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.

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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.

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 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 .~
''~' .

~ ~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 ~' ~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.

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~(~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 . ' '. . . ' , ', ' : . , . ' . ' ' '': .,.'.
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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 .' ---`` ~!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 .

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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 ;`. :
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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 -(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 .;.

,, ' ' ,.

~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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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 , .

. ~, . - . . .

~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 , .
.

. .., :

Claims (29)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A compound of the formula wherein R1 is selected from the group consisting of lower alkyl, lower alkenyl, lower chloroalkyl, trifluoromethyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkylsulfinyl and cyclo-alkyl of from 3 to 7 carbon atoms; R2 is selected from the group consisting of lower alkyl, lower alkenyl, lower chloroalkyl, lower bromoalkyl and wherein R4 and R5 are each selected from the group consisting of hydrogen and lower alkyl; and R3 is selected from the group con-sisting of hydrogen and wherein R6 is selected from the group consisting of lower alkyl, lower chloroalkyl, lower bromoalkyl, lower alkenyl, lower alkynyl, lower alkoxyalkyl, cycloalkyl of from 3 to 7 carbon atoms and wherein X is selected from the group consisting of lower alkyl, halogen, lower haloalkyl, nitro, cyano and lower alkoxy, and m and n are each integers from 0 to 3.

2. The compound of claim 1, tetrahydro-1-(5-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone.

3. The compound of claim 1, tetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-hydroxy-2(1H)-pyrimidinone.

4. The compound of claim 1, tetrahydro-1-(5-methyl-thio-1,3,4-thiadiazol-2-yl)-3-propyl-6-hydroxy-2(1H)-pyrimidinone.

5. The compound of claim 1, tetrahydro-1-(5-methylsulfonyl-1, 3,4-thiadiazol-2-yl)-3-alkyl-6-hydroxy-2(1H)-pyrimidinone.

6. The compound of claim 1, tetrahydro-1-(5-methylsulfinyl-1, 3,4-thiadiazol-2-yl)-3-propargyl-6-hydroxy-2(1H)-pyrimidinone.

7. The compound of claim 1, tetrahydro-1-(5-trifluoro-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone.

8. The compound of claim 1, tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone.

9. The compound of claim 1, which is tetrahydro-1-(5-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-acetyloxy-2(1H)-pyrimidinone.

10. The compound of claim 1, which is tetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-propionyloxy-2(1H)-pyrimidinone.

11. The compound of claim 1, which is tetrahydro-1-(5-methylthio-1,3,4-thiadiazol-2-yl)-3-propyl-6-butanoyloxy-2(1H)-pyrimidinone.

12. The compound of claim 1, which is tetrahydro-1-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-cyclohexyl-carbonyloxy-2(1H)-pyrimidinone.

13. The compound of claim 1, which is tetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-benzoyloxy-2(1H)-pyrimidinone.

14. The compound of claim 1, which is tetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-acetyloxy-2 (1H)-pyrimidinone.

15. The compound of claim 1, which is tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-acetyloxy-2(1H)-pyrimidinone.

16. The compound of claim 1, which is tetrahydro-1-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-acetyloxy-2(1H)-pyrimidinone.

17. The compound of claim 1, which is tetrahydro-1-(5-cyclobutyl-1,3,4-thiadiazol-2-yl)-3-ethyl-6-propionyloxy-2(1H)-pyrimidinone.

18. The compound of claim 1, which is tetrahydro-1-(5-cyclopentyl-1,3,4-thiadiazol-2-yl)-3-propyl-6-butanoyloxy-2(1H)-pyrimidinone.

19. The compound of claim 1, which is tetrahydro-1-(5-cyclohexyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-cyclohexylcarbonyl-oxy-2(1H)-pyrimidinone.

20. The compound of claim 1, which is tetrahydro-1-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-benzoyloxy-2(1H)-pyrimidinone.

21. The compound of claim 1, which is tetrahydro-1-(5-cycloheptyl-1,3,4-thiadiazol-2-yl)-3-methyl-6 acetyloxy-2(1H)-pyrimidinone.

22. The compound of claim 1, which is tetrahydro-1-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-benzoyloxy-2(1H)-pyrimidinone.

23. A method of controlling weeds which comprises contacting said weeds with a herbicidal composition comprising an inert carrier and, as an essential active ingredient, in a quantity toxic to weeds, a compound of claim 1.

24. A process for preparing a compound of the formula wherein R1 is selected from the group consisting of lower alkyl, lower alkenyl, lower chloroalkyl, trifluoromethyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkylsulfinyl 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 wherein R4 and R5 are each selected from the group consisting of hydrogen and lower alkyl, which comprises heating an acetal of the formula wherein R1 and R2 are as described above and R7 and R8 are methyl or ethyl, in a dilute aqueous acidic reaction medium.

25. The process of claim 24 wherein the acetal is heated at a temperature ranging from about 70°C to the reflux temperature of the reaction medium.

26. The process of claim 24 wherein the reaction medium comprises aqueous inorganic acid at a concentration of from about 0.5 to about 5 percent by weight.

27. The process defined in claim 24, including the step of reacting the product thus obtained with an anhydride of the formula wherein R6 is selected from the group consisting of alkyl, halo-alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl and wherein X is selected from the group consisting of alkyl, halogen, haloalkyl, nitro, cyano and alkoxy, and m and n are each integers from 0 to 3; in the presence of a catalytic amount of toluene-sulfonic acid at a temperature of from about 50° to about 90°C to produce a corresponding compound of the formula wherein R1, R2 and R6 are as heretofore dcscribed.

28. The process defined in claim 24, including the step of reacting the product thus obtained with an acid halide of the formula wherein R6 is selected from the group consisting of alkyl, halo-alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl and wherein X is selected from the group consisting of alkyl, halogen, haloalkyl, nitro, cyano and alkoxy, and m and n are each integers from 0 to 3; in the presence of an acid acceptor to produce a corresponding compound of the formula wherein R1, R2 and R6 are as heretofore described.

29. The process of claim 24 wherein the reaction is carried out in an inert organic reaction medium at a temperature of from about 10°to about 30°C.