2-Alkoxy-4-hydroazinopyrimidine compounds and their use in the preparation of 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds

5-Alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2 (3H)-thione compounds, such as 5-ethoxy-8-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione, were prepared by treatment of a 5-alkoxy-1,2,4-triazolo-[4,3-c]pyrimidine-3(2H)-thione compound, such as 5-ethoxy-8-fluoro-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione, with an alkali metal alkoxide in an alcohol solvent selected so that the 5-alkoxy group, the alkoxide, and the alcohol all have the same alkyl group. The trialkylammonium salts of the 5-alkoxy-1,2,4-triazolo [4,3-c]pyrimidine-3(2H)-thione compounds were converted to 3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo-[4,3-c]pyrimidine compounds by reaction with a hydrocarbyl halide, such as benzyl chloride. The products are useful intermediates in the preparation of 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide herbicides.

BACKGROUND OF THE INVENTION 
The present invention relates to 
5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds and to 
their use in the preparation of 
5-alkoxy[1,2,4]-triazolo[1,5-c]pyrimidine-2(3H)-thione compounds and 
3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compounds. It 
further relates to the use of 
3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compounds for 
the preparation of 
2-hydrocarbylthio-5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine compounds. 
5-Alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide compounds that are 
potent herbicides are described in U.S. Pat. No. 5,163,995 and are 
disclosed to be prepared in a multistep process that utilizes 
appropriately substituted 
2-hydrocarbylthio-5-alkylthio-1,2,4-triazolo[4,3-c]pyrimidine compounds as 
intermediates. The preparation requires a substitution reaction wherein 
the alkylthio moiety is replaced with an alkoxy moiety in the presence of 
an ethylenically unsubstituted compound capable of reacting with and 
removing the displaced alkanethiol. This process is lengthy, produces the 
desired products in only moderate yield, and results in a alkylthioethyl 
moiety-containing compound by-product which must be disposed of as waste. 
Improved methods of preparing herbicidal 
5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide compounds, 
including improved methods for preparing intermediates that are useful in 
their preparation, would be of considerable value as would the 
intermediates that would be required to implement the improved methods. 
Neither 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds nor 
5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione compounds have been 
described in the art. 
3-Hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compounds are 
also novel. 
SUMMARY OF THE INVENTION 
5-Alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds have now 
been prepared and found to be useful in the preparation of 
5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione compounds by 
rearrangement and, as a result, can be used as intermediates in the 
preparation of N-(substituted 
phenyl)-5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide herbicides. 
The resulting process allows for the preparation of N-(substituted 
phenyl)-5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide herbicides 
in a more economical and more readily carried out manner than the 
previously described process. 
The invention includes 
5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds of Formula 
I: 
##STR1## 
wherein one of Y and Z represents F, Cl, Br, R', or OR' and the other 
represents H; and 
R and R' each independently represents CH.sub.3 or C.sub.2 H.sub.5 
and their trialkylammonium salts, which salts are adducts of said compounds 
and a trialkylamine compound having a pKa of about 9.4 to about 11.4. 
Compounds of Formula I wherein one of Y and Z represents F, Cl, or Br and 
the other represents H are generally preferred. The fluorinated compounds 
are usually more preferred, but the chlorinated compounds are sometimes 
more preferred. Trialkylammonium salts wherein the trialkylamine involved 
is a compound of Formula II: 
##STR2## 
wherein R.sup.1, R.sup.2, and R.sup.3 each independently represents 
C.sub.1 -C.sub.4 alkyl or benzyl or two of R.sup.1, R.sup.2, and R.sup.3 
together represent a moiety of the formula --(CH.sub.2).sub.4 --, 
--(CH.sub.2).sub.5 --, O(C.sub.2 H.sub.4 --).sub.2, or CH.sub.3 N(C.sub.2 
H.sub.4 --).sub.2 or all three of R.sup.1, R.sup.2, and R.sup.3 together 
represent a moiety of the formula N(C.sub.2 H.sub.4 --).sub.3 are 
preferred salts; triethylammonium salts are specifically preferred. 
The invention further includes a method of use of 
5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds of Formula 
I: 
##STR3## 
wherein one of Y and z represents F, Cl, Br, R', or OR' and the other 
represents H; and 
R and R' each independently represents CH.sub.3 or C.sub.2 H.sub.5 
which method comprises treating said compound with at least about one molar 
equivalent of an alkali metal alkoxide of the formula ROM wherein R 
represents CH.sub.3 or C.sub.2 H.sub.5 and M represents an alkali metal in 
a medium containing an alcohol of the formula ROM wherein R represents 
CH.sub.3 or C.sub.2 H.sub.5, the alkali metal alkoxide and the alcohol 
selected so that R is the same in the alkali metal alkoxide, the alcohol, 
and the 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compound, at 
a temperature of about -10.degree. C. to about 40.degree. C., and 
thereafter acidifying the mixture to obtain a 
5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione compound of Formula 
III: 
##STR4## 
wherein R, Y, and Z are as defined before. 
Compounds of Formula III wherein one of Y and Z represents F, Cl, or Br and 
the other represents H are preferred. Those wherein one of Y and Z 
represents F and the other represents H are usually more preferred and 
those wherein one of Y and Z represents Cl and the other represents H are 
sometimes more preferred. 
The invention still further includes a method of use of trialkylammonium 
salts of 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds, 
which salts are adducts of a compound of Formula I: 
##STR5## 
wherein one of Y and Z represents F, Cl, Br, R', or OR' and the other 
represents H; and 
R and R' each independently represents CH.sub.3 or C.sub.2 H.sub.5 
and a trialkylamine compound having a pKa of about 9.4 to about 11.4, which 
method comprises treating said salt with at least about an equimolar 
amount of a benzyl halide or a C.sub.2 -C.sub.4 alkyl halide in an inert 
solvent and obtaining a 
3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compound of 
Formula IV: 
##STR6## 
wherein X, Y, and R are defined as before and R.sup.4 represents benzyl or 
C.sub.2 -C.sub.4 alkyl. 
Compounds of Formula IV wherein one of Y and Z represents F, Cl, or Br and 
the other represents H are usually preferred. Those wherein one of Y and Z 
represents F and the other represents H are usually more preferred and 
those wherein one of Y and z represents C.sub.1 and the other represents H 
are sometimes more preferred. Compounds wherein R.sup.4 represents benzyl 
are typically preferred. 
3-Hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compounds of 
Formula IV can be converted to corresponding 
2-hydrocarbylthio-5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine compounds of 
Formula V: 
##STR7## 
by treatment with an alkali metal alkoxide of the formula ROM wherein R 
represents CH.sub.3 or C.sub.2 H.sub.5 in a medium containing an alcohol 
of the formula ROH wherein R represents CH.sub.3 or C.sub.2 H.sub.3 ; the 
alkali metal alkoxide and the alcohol selected so that R is the same in 
the alkali metal alkoxide, the alcohol, and the 
3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compound. 
DETAILED DESCRIPTION OF THE INVENTION 
The compounds of the present invention can be characterized as 
5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds wherein 
the alkoxy group is methoxy or ethoxy and wherein there is a single 
halogen, alkyl, or alkoxy substituent in the 7- or 8-position and the 
reaction products of these compounds with trialkylamine compounds. They 
include 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds of 
Formula I: 
##STR8## 
wherein R represents methyl or ethyl and one of Y and Z represents 
fluorine, chlorine, bromine, methyl, ethyl, methoxy, or ethoxy and the 
other represents hydrogen and their trialkylammonium salts. 5-Alkoxy-(7- 
or 8-fluoro, chloro, or 
bromo)-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds are often 
preferred. The fluorinated compounds are typically more preferred but the 
chlorinated compounds are sometimes more preferred. 
Some specifically preferred compounds of Formula I include 
5-ethoxy-7-(fluoro or chloro)-1,2,4-triazolo 
[4,3-c]pyrimidine-3(2H)-thione, 5-methoxy-7-(fluoro or 
chloro)-1,2,4-triazolo[4,3-c]-pyrimidine-3 (2H)-thione, 5-ethoxy-8-(fluoro 
or chloro)-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione, and 
5-methoxy-8-(fluoro or 
chloro)-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione. 
The compounds of Formula I are named and depicted herein as 3(2H)-thione 
compounds. They could equally well have been named and depicted as 3-thiol 
compounds since the two structures are keto-enol type isomers and are in 
dynamic equilibrium. The keto and enol isomers of the compounds of Formula 
I are shown below: 
##STR9## 
The trialkylammonium salts of the compounds of Formula I can be looked upon 
as adducts of these compounds and a trialkylamine compound having a pKa of 
about 9.4 to about 11.4, such as a trialkylamine compound of Formula II: 
##STR10## 
wherein R.sup.1, R.sup.2, and R.sup.3 each independently represents alkyl 
of 1 to 4 carbon atoms or benzyl or two of R.sup.1, R.sup.2, and R.sup.3 
together, taken with the nitrogen atom, represent pyrrolidine, piperidine, 
morpholine, or N-methylpiperazine or all three of R.sup.1, R.sup.2, and 
R.sup.3 together, taken with the nitrogen atom, represent 
1,4-diazabicyclo[2,2,21octane. The triethylammonium salts are preferred 
salts. 
The 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds of 
Formula I are not very stable and tend to decompose on standing, even in 
the solid state. It is preferred to utilize these compounds as 
intermediates in the synthesis of other, more stable compounds, soon after 
preparing them. 
The 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds of the 
present invention can be employed in a process for the preparation of 
5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione compounds of Formula 
III: 
##STR11## 
wherein R represents methyl or ethyl and one of Y and Z represents fluoro, 
chloro, bromo, methyl, ethyl, methoxy, or ethoxy and the other represents 
hydrogen. These compounds can be characterized as 
1,2,4-triazolo[1,5-c]-pyrimidine-2(3H)-thione compounds having a methoxy 
or an ethoxy substituent in the 5-position and a halo, alkyl, or alkoxy 
substituent in the 7- or 8-position. The process involved in the method of 
use is preferably employed to prepare compounds of Formula III wherein one 
of Y and Z represents fluoro, chloro, or bromo and the other represents 
hydrogen. It is of special interest for the preparation of compounds of 
Formula III wherein one of Y and Z represents fluoro and the other 
represents hydrogen and is of considerable interest for compounds wherein 
one of Y and Z represents chloro and the other represents hydrogen. 
Some specifically preferred compounds of Formula III that can be prepared 
include 8-fluoro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione, 
5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione, 
8-chloro-5-methoxy[1,2,4,]triazolo[1,5-c]pyrimidine- 2(3H)-thione, and 
7-chloro-5-ethoxy[1,2,4 ]triazolo[1,5-c]pyrimidine-2 (3H) -thione. 
The compounds of Formula III are named and depicted herein as 2(3H)-thione 
compounds. They could equally well have been named and depicted as 2-thiol 
compounds since the two structures are keto-enol type isomers and are in 
dynamic equilibrium. The keto and enol isomers of the compounds of Formula 
III are shown below: 
##STR12## 
The process by which compounds of Formula I are converted to compounds of 
Formula III involves combining a 
5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compound of Formula 
I: 
##STR13## 
wherein R represents methyl or ethyl and one of Y and z represents fluoro, 
chloro, bromo, methyl, ethyl, methoxy, or ethoxy and the other represents 
hydrogen with at least about one molar equivalent of an alkali metal 
methoxide or ethoxide in an medium containing methanol or ethanol as the 
solvent or one of the solvents. The alkali metal alkoxide and the alcohol 
must be selected so that the 5-alkoxy group of the compound of Formula I, 
the alkoxide, and the alcohol all have the same alkyl group (methyl or 
ethyl). If the reagents are not so matched, exchange reactions take place 
which significantly reduce yields and complicate the recovery procedure. 
The alkali metal alkoxides that are employed in the process are the 
lithium, sodium, and potassium derivatives of methanol and ethanol. At 
least about one molar equivalent of the alkali metal alkoxide is employed. 
Ratios of alkali metal alkoxide to the compound of Formula I of between 
about 1 and about 2 are typical. Ratios of about 1.03 to about 1.3 are 
generally preferred. Higher concentrations of alkali metal alkoxide are 
deleterious to the process. 
The reaction medium of the process must contain the appropriate alcohol and 
may also contain other compatible solvents. Such solvents should be 
miscible with the alcohol involved, should not cause excessive 
precipitation of the alkali metal alkoxide, and should not be reactive 
with any of the reagents or products. Such compatible solvents include 
acetonitrile, 1,2-dimethoxyethane, N,N-dimethylformamide, dimethyl 
sulfoxide, and the like. It is preferred that the reaction medium contain 
less than about 2 percent water. It is more preferred that it contains 
less than 0.2 percent. The presence of water is responsible for side 
reactions that destroy the starting material, the product, or both. It is 
often preferred to use as little reaction medium as possible; complete 
solubility of the compounds of Formulas I and III in the medium is not 
required. 
The isomerization proceeds well at ambient temperatures and is generally 
carried out at temperatures of about -10.degree. C. to about 40.degree. C. 
Temperatures of about 0.degree. C. to about 30.degree. C. are often 
preferred. The starting materials and products tend to decompose at higher 
temperatures. The fact that the process can be carried out at such low and 
convenient temperatures is an important feature of the process. 
The process can be carried out in conventional vessels. The reaction 
mixture is typically agitated to ensure good mixing. 
The rearrangement reaction takes place over the course of a few minutes to 
a few hours and a mixture containing an alkali metal salt of a compound of 
Formula III is initially obtained. It is preferred that this mixture not 
be allowed to stand for extensive periods of time because the salts of the 
desired compound of Formula III are not completely stable. The compounds 
of Formula III, themselves, are obtained by adding sufficient acid to 
neutralize the medium. 
Essentially any organic or inorganic protic acid can be used for the 
acidification. Typically, a cheap and readily available acid having a pKa 
of less than 8, such as hydrochloric acid, sulfuric acid, or acetic acid 
is used. Hydrochloric acid is preferred. Typically, an amount of acid in 
excess of that required for exact neutralization is added. 
The desired compound of Formula III can be recovered by collecting the 
precipitate that forms upon acidification. Water is typically added after 
acidification and before the collection to ensure complete precipitation. 
The recovered product can be collected by filtration or centrifugation and 
can be dried by conventional means, if desired, provided that excessive 
heat is avoided. These compounds can be further purified by conventional 
means, such as by recrystallization, liquid chromatography, and the like. 
They are not very stable, however, and tend to decompose on standing, even 
in the solid state. It is preferred to utilize these compounds as 
intermediates in the synthesis of other, more stable compounds soon after 
preparing them. 
The compounds of Formula III can be converted to 
2-hydrocarbylthio-5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine compounds of 
Formula V: 
##STR14## 
wherein R represents methyl or ethyl; one of X and Y represents fluoro, 
chloro, bromo, methyl, ethyl, methoxy, or ethoxy and the other represents 
hydrogen; and R.sup.4 represents benzyl or C.sub.2 -C.sub.4 alkyl. The 
conversion is effected by treating the compound of Formula III with a 
base, such as a triethylamine compound, sodium ethoxide, or potassium 
methoxide, and a benzyl halide or a C.sub.2 -C.sub.4 alkyl halide, such as 
benzyl chloride or ethyl bromide, or a substantial equivalent thereof 
under mild reaction conditions. The reaction is typically carried out in 
methanol or ethanol solvent at ambient temperature or at a temperature up 
to about 50.degree. C. with agitation to ensure mixing. Methanol and an 
alkali metal methoxide are preferably employed as the solvent and base, 
respectively, when the R of Formula III represents methyl and ethanol and 
an alkali metal alkoxide are, preferably, employed when R represents 
ethyl. Sodium alkoxides are preferred alkali metal alkoxides. The reaction 
conditions are essentially the same as those of similar alkylation 
reactions well-known in the art. 
It is often convenient to convert the alkali metal salt of a compound of 
Formula III that is initially obtained in the method of use of compounds 
of Formula I process of the present invention into a compound of Formula V 
by adding a benzyl halide or a C.sub.2 -C.sub.4 alkyl halide, such as 
benzyl chloride or ethyl bromide, or a substantial equivalent thereof to 
the reaction mixture rather than acidifying. The alkylation reaction can 
be carried out under the same reaction conditions already established in 
the reaction vessel or can be altered within the guidelines given above 
for optimum results. The compounds of Formula V obtained can be recovered 
by conventional means. 
The trialkylammonium salts of 
5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds that are 
adducts of a compound of Formula I: 
##STR15## 
wherein R represents methyl or ethyl and one of Y and Z represents fluoro, 
chloro, bromo, methyl, ethyl, methoxy, or ethoxy and the other represents 
hydrogen and a trialkylamine compound having a pKa of about 9.4 to about 
11.4 such as, but not limited to, a compound of Formula II: 
##STR16## 
wherein R.sup.1, R.sup.2, and R.sup.3 each independently represents 
C.sub.1 -C.sub.4 alkyl or benzyl or two of R.sup.1, R.sup.2, and R.sup.3 
together along with the nitrogen atom represent pyrrolidine, piperidine, 
morpholine, or N-methylpiperazine or all three of R.sup.1, R.sup.2, and 
R.sup.3 together along with the nitrogen atom represent 
1,4-diazabicyclo[2,2,21]octane can be employed for the preparation of a 
3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine derivative 
compounds of Formula IV: 
##STR17## 
wherein X, Y, and R are defined as before and R.sup.4 represents benzyl or 
C.sub.2 -C.sub.4 alkyl. The use of trialkylammonium salts of compounds of 
Formula I wherein one of Y and Z represents fluoro, chloro or bromo and 
the other represents hydrogen are preferred. The use of such compounds 
wherein one of Y and z represents fluoro and the other represents hydrogen 
are usually more preferred and those wherein one of Y and z represents 
chloro and the other represents hydrogen are sometimes more preferred. The 
trialkylammonium salts derived from compounds of Formula II are usually 
preferred and triethylammonium salts (R.sup.1, R.sup.2, and R.sup.3 each 
represent ethyl) are normally employed. The conversion of the salts to 
3-benzylthio compounds (R.sup.4 in Formula IV represents benzyl) is 
generally preferred. 
The method is accomplished by combining a trialkylammonium salt of a 
compound of Formula I with a benzyl halide or a 2 to 4 carbon alkyl 
halide, such as benzyl chloride or ethyl bromide, or-a substantial 
equivalent thereof in a solvent in which the salt is at least partially 
soluble, such as acetonitrile/water, methanol, or ethanol, and allowing 
the mixture to stand at ambient temperature or heating it to about 
40.degree. C. to about 80.degree. C. Excessive heating and large excesses 
of trialkylamine compound lead to undesirable side reactions. The reaction 
conditions are essentially the same as those known in the art for related 
alkylation reactions. The resulting compounds of Formula IV can be 
recovered by conventional means, such as by filtration or by evaporation 
of the solvents, and can be purified readily by conventional means, such 
as by liquid chromatography, recrystallization from a solvent, or 
extraction. 
The trialkylammonium salt compounds employed in this method of use can be 
obtained by the reaction of a 2-alkoxy-4-hydrazinopyrimidine compound, 
carbon disulfide, and hydrogen peroxide in the presence of a trialkylamine 
compound as described hereinbelow. These compounds can also be obtained by 
the reaction of a compound of Formula I with a trialkylamine compound, 
such as a compound of Formula II. This preparation can be accomplished 
readily by dissolving a compound of Formula I in an organic solvent, such 
as acetonitrile, and adding at least about one mole of the trialkylamine 
compound. If a solvent in which the compound of Formula I is soluble but 
the trialkylammonium salt is insoluble is selected, the salt precipitates 
and can be recovered by filtration or centrifugation. The recovered salts 
can be dried by conventional means. If a solvent in which the salt is 
soluble, such as a 1:1 mixture of acetonitrile and water, is selected, the 
salt remains in solution and can be utilized in that form. 
The 3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compounds of 
Formula IV can be converted into 
2-hydrocarbylthio-5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine compounds of 
Formula V: 
##STR18## 
wherein R represents methyl or ethyl and one of Y and Z represents fluoro, 
chloro, bromo, methyl, ethyl, methoxy, or ethoxy and the other represents 
hydrogen by treatment with an alkali metal alkoxide under reaction 
conditions similar to those described hereinabove for the conversion of a 
compound of Formula I into a compound of Formula III except that less that 
an equimolar amount of the alkali metal alkoxide is required and the 
product is not a salt and does not require neutralization with an acid 
before recovery. Mole ratios of alkali metal alkoxide to compound of 
Formula IV of about 1:100 to about 1:1 are generally employed. Mole ratios 
of about 1:50 to about 1:4 are usually preferred. The isomerization is 
typically carried out in a medium containing an alcohol solvent. It is 
important that any alcohol in the medium, the alkali metal alkoxide, and 
the R of the compound of Formula IV all have the same alkyl group. Thus, 
when R represents methyl, an alkali metal methoxide and methanol are 
employed and when R represents ethyl an alkali metal ethoxide and ethanol 
are employed. Temperatures between about 0.degree. C. and about 60.degree. 
C. are typical; temperatures between about 10.degree. C. and about 
50.degree. C. are usually preferred. The mixture is typically agitated 
during the reaction period to ensure good mixing. The compounds of Formula 
V can be recovered by conventional means, such as by adding water to 
ensure complete precipitation and subsequent filtration or centrifugation. 
The compounds of Formula V are known from U.S. Pat. Nos. 5,163,995 and 
5,177,206, the appropriate portions of which are hereby incorporated by 
reference, to be useful for the preparation of herbicidal 
5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide compounds. The 
compounds of Formula V can be converted to the corresponding 
2-chlorosulfonyl compounds by treatment with chlorine in an aqueous medium 
and the 2-chlorosulfonyl compounds can be coupled with an appropriately 
substituted aniline or N-trialkylsilylaniline compound in an inert 
solvent, such as acetonitrile, in the presence of a tertiary amine and/or 
a catalytic amount of dimethyl sulfoxide. The compounds of Formula III can 
be converted directly into herbicidal 
5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide compounds in a 
similar manner. 
Alternately, and usually preferably, the compounds of Formula III can be 
converted into herbicidal 
5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide compounds by 
oxidation with hydrogen peroxide to obtain a 
2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine) intermediate 
compound of Formula VI: 
##STR19## 
wherein R, Y, and Z are as defined before. These intermediates can be 
subsequently chloroxidized with chlorine in an aqueous medium to obtain 
the 2-chlorosulfonyl intermediates noted above. The oxidation is generally 
carried out by adding slightly in excess of 0.5 mole (1 equivalent) of 
hydrogen peroxide to the compound of Formula III in an aqueous solvent, 
such as aqueous acetonitrile, at ambient temperatures. The compound of 
Formula VI, which typically precipitates from the medium, can be 
recovered. It can be converted to a 2-chlorosulfonyl intermediate by 
treatment with chlorine in an aqueous medium, such as aqueous methylene 
chloride, at ambient temperatures or below. The 2-chlorosulfonyl 
intermediates can be converted to the desired herbicides by the methods 
described in the prior art cited above. 
The 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds of 
Formula I can be prepared by combining a 2-alkoxy-4-hydrazinopyrimidine 
compound of Formula VII: 
##STR20## 
wherein R represents methyl or ethyl and one of Y and Z represents fluoro, 
chloro, bromo, methyl, ethyl, methoxy, or ethoxy and the other represents 
hydrogen with at least about one mole of carbon disulfide and, optionally, 
a trialkylamine compound having a pKa of about 9.4 to about 11.4, such as 
a compound of Formula II: 
##STR21## 
wherein R.sup.1, R.sup.2, and R.sup.3 each independently represents 
C.sub.1 -C.sub.4 alkyl or benzyl or two of R.sup.1, R.sup.2, and R.sup.3 
together represent a moiety of the formula --(CH.sub.2).sub.4 --, 
--(CH.sub.2).sub.5 --, O(C.sub.2 H.sub.4 --).sub.2, or CH.sub.3 N(C.sub.2 
H.sub.4 --).sub.2 or all three of R.sup.1, R.sup.2, and R.sup.3 together 
represent a moiety of the formula N(C.sub.2 H.sub.4 --).sub.3. The 
reagents are combined in a suitable inert liquid medium, such as aqueous 
acetonitrile, and at least about one mole of an oxidizing agent, such as 
hydrogen peroxide, is added at a temperature of about 0.degree. C. to 
about 40.degree. C. The mixture is typically agitated to assure good 
mixing. The reaction proceeds quickly with the formation the desired 
5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compound of Formula 
I or, if a trialkylamine compound is added, a trialkylammonium salt 
thereof. If a trialkylammonium salt is obtained, it can be converted into 
a compound of Formula I by adding at least one mole of a strong acid, such 
as hydrochloric acid. The compounds of Formula I obtained can be recovered 
by adding water to ensure complete precipitation and collecting the 
precipitate by filtration or centrifugation. The by-product elemental 
sulfur can be removed by conventional means. The differences in solubility 
between sulfur and the compounds of Formula I in aqueous bases (compound 
of Formula I soluble and sulfur insoluble) and in carbon disulfide (the 
opposite) are typically exploited. 
The 2-alkoxy-5-substituted-4-hydrazinopyrimidine starting materials of 
Formula VII can be prepared from 2,4-dialkoxy-5-substituted-pyrimidine 
compounds by treatment with hydrazine and triethylamine. Similarly, the 
2-alkoxy-6-substituted-4-hydrazinopyrimidine compounds can be prepared 
from the corresponding 2-alkoxy-4-halo-6-substituted-pyrimidine compounds 
by treatment with hydrazine and triethylamine. The reactions are best 
carried out in water or in a solvent, such as acetonitrile, at a 
temperature of between about 0.degree. C. about 40.degree. C., using about 
one mole of triethylamine and slightly in excess of one mole of hydrazine 
hydrate. The desired 2-alkoxy-(5 or 6)-substituted-4-hydrazinopyrimidine 
compounds of Formula VII can be recovered by adding water to promote 
precipitation and recovering the precipitate by filtration, 
centrifugation, or extraction. These compounds can, however, often be 
employed as intermediates without recovery and/or purification.

The following examples are presented to illustrate the invention. They 
should not be construed as limitations on the claims. 
EXAMPLES 
1. Preparation of 5-Fluoro-4-hydrazino-2-methoxyprimidine 
5-Fluoro-2,4-dimethoxypyridine (158 g (grams), 1.00 mol), 150 g (3.00 mol) 
of hydrazine hydrate, and 237 g of methanol were placed in a 1 L (liter) 
flask and heated to reflux (about 70.degree. C.) for 3.5 hours with 
stirring. The mixture, which became homogeneous and then heterogeneous 
again, was then cooled to 0.degree.-5.degree. C. and the solids present 
were recovered by vacuum filtration, washed with 150 mL (milliliters) of 
cold methanol, and dried to constant weight. The title compound, which was 
obtained as colorless needles melting at 188.degree.-189.degree. C., 
amounted to 151.5 g (98 percent of theory). 
NMR data (DMSO-d6) .delta.: .sup.1 H: 3.77 (s, 3H), 4.38 (2H), 7.83 
(d(J=3.6 Hz), 1H), 8.87 (1H); .sup.13 C: 54.2,137.9 (d(J.sub.CF =19.6 Hz 
)), 141.5 (d(J.sub.CF =244.8 Hz )), 154.3 (d(J.sub.CF =13.7 Hz )), 160.6. 
2. Preparation of 2ethoxy-4-fluoro-6-hydrazinopyrimidine 
A mixture of 100 g of 94 percent purity (0.59 mol) 
2-ethoxy-4,6-difluoropyrimidine, 275 mL of acetonitrile, and 107 g of 
water was prepared and cooled to 10.degree. C. To this was added 68 g 
(0.67 mol) of triethylamine and then 34 g (0.68 mol) of hydrazine hydrate, 
slowly with stirring and cooling (at 5.degree. to 10.degree. C.). When all 
of the hydrazine had been added, the mixture was stirred another 15 min 
with cooling and was then allowed to warm. After a total of 1 hour, the 
solids that formed were recovered by vacuum filtration and were washed 
twice with 100 mL portions of water and then with 50 mL of ethanol. The 
title compound, which was obtained as a white solid melting at 
141.degree.-143.degree. C., amounted to 79.7 g (80 percent of theory). 
Elemental Analysis for C.sub.6 H.sub.9 FN.sub.4 O: Calc.: %C, 41.9; %H, 
5.27; %N, 32.5 Found: %C, 42.2; %H, 5.12; %N, 32.6 
3. Preparation of 5-Chloro-4.-hydrazino-2-methoxypyrimidine 
A solution containing 0.35 g (2.0 mmol) of 5-chloro-2,4-dimethoxypyrimidine 
and 0.35 g (7.0 mmol) of hydrazine hydrate in 2.9 g of methanol was heated 
at reflux with stirring for 8 hours. The mixture was then cooled causing a 
precipitate to form. Water was added until the precipitation appeared to 
be complete and the precipitate was then recovered by vacuum filtration 
and allowed to air dry overnight to obtain 0.23 g (66 percent of theory) 
of the title compound as a white solid. The product melted at 
172.degree.-173.degree. C. after changing crystalline form from needles to 
cube-like shapes in a phenomenon that appeared to involve sublimation. 
NMR data (DMSO-d6) .delta.: .sup.1 H: 3.85 (s, 3H), 4.50 (2H), 7.97 (s, 
1H), 8.7 (1H); .sup.13 C: 54.17, 105.40, 152.77, 159.39, and 163.39. 
4. Preparation of 
8-Fluoro-5-methoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione 
5-Fluoro-4-hydrazino-2-methoxypyrimidine (15.81 g, 0.100 mol), 47 g of 
methanol, 10.2 g (0,100 mol) of triethylamine, and 11.4 g (0.15 mol) of 
carbon disulfide were combined in a 250 mL flask under nitrogen at ambient 
temperature with stirring to obtain a yellow, heterogeneous mixture. The 
mixture was cooled to 15.degree. C. with an ice bath. Hydrogen peroxide 
(12.5 g of 30 percent aqueous, 0.11 mol) was then added by means of a 
syringe pump, the syringe of which was inserted into the flask through a 
septum. The addition was made over a 1-hour period with stirring and 
cooling to maintain the temperature at about 15.degree. C. The mixture was 
allowed to react and warm for 1 hour and the resulting heterogeneous 
orange mixture was vacuum filtered to remove the solid sulfur. The 
filtrate was cooled in an ice bath and acidified with 17.6 mL (0.11 mol) 
of 6.25N hydrochloric acid diluted with 125 mL of water. The resulting 
precipitate was recovered by vacuum filtration and dried under reduced 
pressure to obtain 18.81 g (94 percent of theory) of the title compound as 
an off-white solid melting at 166.degree. C. with decomposition. 
NMR data (DMSO-d6) .delta.: .sup.1 H: 4.01 (s, 3H), 7.64 (d(J=2.8 Hz), 1H), 
14.5 (brs, 1H); .sup.13 C: 56.00, 125.6 (d(J.sub.CF =22.0 Hz)), 141.6, 
141.7 (d(J.sub.CF =41.7 Hz)), 146.0 (d(J.sub.CF =191.0 Hz)), and 161.2. 
5. Preparation Of 5-Ethoxy-7-fluoro-2,4-triazolo[4,3-c 
]pyrimidine-3(2H)-thione 
Procedure A: A mixture containing approximately 5.2 g (30 mmol) of 
2-ethoxy-4-fluoro-6-hydrazinopyrimidine in a solvent composed of 50 mL of 
acetonitrile and 15 mL of water was prepared and to this was added 6.4 mL 
(107 mmol) of carbon disulfide at ambient temperature with stirring. The 
heterogeneous white mixture became a pale yellow solution after about 10 
min and then 3.8 mL of 30 percent aqueous hydrogen peroxide (37 mmol) and 
3.2 mL of water were added over a 30-min period with stirring and cooling 
to hold the temperature at about 25.degree. C. The mixture was allowed to 
react another 10 min and then 3.22 g (32 mmol) of triethylamine was added 
and the resulting mixture was filtered to remove sulfur. The filtrate was 
acidified with 10 mL of 3.75N hydrochloric acid (38 mmol) and the 
resulting mixture was filtered to recover the precipitate that formed. 
This was washed with water and dried to obtain 4.4 g (66 percent of 
theory) of the title compound of 97 percent purity as a light beige solid 
melting at 170.degree. C. Considerable product remained in the filtrate. 
Elemental Analysis for C.sub.7 H.sub.7 FN.sub.4 OS: Calc.: %C, 39.2; %H, 
3.29; %N, 26.2 Found: %C, 39.3; %H, 3.07; %N, 25.9 
Procedure B: A mixture containing 32.6 g (0,186 mol) of 
2-ethoxy-4-fluoro-6-hydrazinopyrimidine and 21.1 g (0.277 mol) of carbon 
disulfide in a solvent composed of 83.7 mL of acetonitrile and 33.3 mL of 
water was prepared under nitrogen in a 500 mL flask equipped with a 
condensor and an opening covered by a septum through which the syringe of 
a syringe pump was inserted. The mixture was allowed to react with 
stirring at ambient temperature for 15 min and then 22.2 g of 30 percent 
aqueous hydrogen peroxide (0.196 mol) was added over a 1-hour period by 
means of the syringe with stirring and cooling to hold the temperature at 
about 25.degree. C. The mixture was allowed to react for another hour and 
then was cooled to about 0.degree. C. The precipitated product and sulfur 
by-product were recovered by vacuum filtration and washed with 150 mL of 
water, 150 mL of a 1:1 mixture of water and acetonitrile, and finally with 
two 75 mL portions of acetonitrile and were then air dried to obtain 45.1 
g of a light beige product that was 74.8 percent the title compound (85 
percent of theory yield), 13.9 percent sulfur, and 0.5 percent water. 
6. Preparation of 5-Ethoxy-7-fluoro-1,2, 
4-triazolo[4,3-c]pyrimidine-3(2H)-thione From 
2-ethoxy-4,6-difluoropyrimidine 
A mixture consisting of 1.42 parts of acetonitrile, 2.66 parts of water, 
1.60 parts of 2-ethoxy-4,6-difluoropyrimidine, and 1.06 parts of 
triethylamine is prepared and cooled to 5.degree. C. Hydrazine hydrate 
(0.526 parts is added with cooling and stirring under nitrogen at a rate 
such that the temperature does not rise above 10.degree. C. When the 
addition is complete, the mixture is allowed to warm to ambient 
temperature and stir until the reaction is complete. Carbon disulfide 
(1.14 parts) is then added with stirring and the mixture is allowed to 
react for 15 min. Hydrogen peroxide as a 30 percent solution in water 
(1.20 parts) is then added with stirring and cooling to maintain the 
temperature between 25.degree. and 30.degree. C. and the mixture is 
allowed to react for an additional hour at 25.degree. C. The mixture is 
cooled to 0.degree. C. and filtered in a reduced pressure apparatus to 
recover the insoluble material. This material is washed sequentially with 
3.20 parts of water and 4.00 parts of cold acetonitrile to obtain the 
title compound mixed with by-product sulfur and containing up to 2 percent 
water and some acetonitrile. 
7. Preparation of 7-Chloro-5-ethoxy-1,2,4-triazolo[4,3-C 
]pyrimidine-3(2H)-thione 
A mixture containing 20 g of 93 percent purity (99 mmol) 
4-chloro-2-ethoxy-6-hydrazinopyrimidine in a solvent composed of 90 mL of 
acetonitrile and 26 mL of water was prepared under nitrogen in a 500 mL 
flask equipped with a condensor and an opening covered by a septum through 
which the syringe of a syringe pump was inserted. To this was added 11.3 g 
(148 mmol) of carbon disulfide and, after a 15-min reaction period, 16.7 g 
of 30 percent aqueous hydrogen peroxide (147 mmol) was added over a 15-min 
period by means of the syringe with stirring and cooling to hold the 
temperature at about 25.degree. C. The mixture was allowed to react for 
another 4 hours and then was cooled to about 0.degree. C. The precipitated 
product and sulfur by-product were recovered by vacuum filtration and 
washed with water, a 1:1 mixture of water and acetonitrile, and finally 
acetonitrile. The wet cake was slurried in 1 L of water at 70.degree. C. 
and about 600 mL of acetonitrile was added to dissolve the solid. The 
resulting mixture was gravity filtered and the filtrate was allowed to 
cool over the weekend. The mixture was further cooled in a refrigerator 
and the crystals that formed were recovered by vacuum filtration, washed 
with acetonitrile, and dried to constant weight to obtain 14.1 g (62 
percent of theory) of the title compound as an amber solid which 
decomposed on heating above 187.degree. C. 
Elemental Analysis for C.sub.7 H.sub.7 ClN.sub.4 OS: Calc.: %C, 36.4; %H, 
3.06; %N, 24.3 Found: %C, 36.4; %H, 2.79; %N, 24.1 
8. Preparation of 
8-Chloro-5-methoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione 
5-Chloro-4-hydrazino-2-methoxypyrimidine (17.45 g, 0.10 mol) and 25 g 
(0.033 mol) of carbon disulfide were combined in 120 mL of acetonitrile 
and 30 mL of water at ambient temperature with stirring and 11.4 g (0.10 
mol) of 30 percent hydrogen peroxide was added to the resulting mixture 
with stirring over a 2-hour period. The temperature rose from 20.degree. 
C. to 48.degree. C. Analysis of the mixture by high pressure liquid 
chromatography (HPLC) indicated that the reaction was complete. A 79.8 g 
(47.2 percent of the total) portion of the reaction mixture was diluted 
with 50 mL of water and the mixture was acidified with hydrochloric acid. 
The solids present were then recovered by vacuum filtration and dried to 
obtain 10.15 g of a mixture of the title compound and sulfur. The sulfur 
was then removed by extracting the solids with 45 g of carbon disulfide to 
obtain 8.08 g (80 percent of theory) of the title compound as a tan 
powder. This material was 92 percent pure by HPLC analysis; it decomposed 
on heating. 
NMR data (DMSO-d6) .delta.: .sup.1 H: 4.04 (s, 3H), 7.67 (s, 1H), 14.25 
(brs, 1H); .sup.13 C: 56.18, 110.08, 140.46, 145.76, 150.11, and 161.32. 
9. Preparation of 
3-Benzylthio-8-fluoro-5-methoxy-1,2,4-triazolo[4,3-c]pyrimidine and 
2-Benzylthio-8-fluoro-5-methoxyl[1,2,4]triazolo[1,5-c]pyrimidine 
5-Fluoro-4-hydrazino-2-methoxypyrimidine (29.7 g, 0.188 mol), 100 g of 
methanol, 19.2 g (0.188 mol) of triethylamine, and 28.9 g (0.38 mol) of 
carbon disulfide were combined in a 500 mL flask under nitrogen at ambient 
temperature. Hydrogen peroxide (27 g of 30 percent aqueous, 0.24 mol) was 
then added by means of a syringe pump, the syringe of which was inserted 
into the flask through a septum, with cooling to maintain the temperature 
at 17.degree. to 22.degree. C. and with stirring. The addition was made 
over a 1.6-hour period. The mixture was allowed to react for another 1.5 
hour and the resulting heterogeneous orange mixture was vacuum filtered to 
remove the solid sulfur. The solids were washed with 100 g of methanol and 
the filtrate (including the wash methanol), which contained the 
triethylammonium salt of 
8-fluoro-5-methoxy-1,2,4-triazolo[4,3-c]-pyrimidine-3(2H)-thione, was 
transferred to a reaction flask. Benzyl chloride (24.1 g, 0.19 mol) was 
added at 21.degree. C. with stirring. There was a mild exotherm which 
increased the temperature to 27.degree. C. and, after about 30 min, a 
precipitate began to form. After 1 hour, 130 g of methanol was removed by 
distillation under about 600 Pascals pressure and the heterogeneous 
residue was subsequently cooled to about 5.degree. C. and vacuum filtered 
to recover the insoluble solids. About 25 g of methanol was used to aid in 
the transfer of the mixture and to wash the precipitate. The wet cake 
obtained amounted to 55.8 g and contained approximately 42 g (0.14 mol, 
approximately 95 percent of theory) of 3-benzylthio-8-fluoro-5 
-methoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione. 
NMR data (CDCl.sub.3) .delta.: .sup.1 H: 4.11 (s, 3H), 4.61 (s, 2H), 7.3 
(m, 4H), and 7.4 (m, 2H); .sup.13 C: 36.7, 56.5, 123.3,123.6, 127.8, 
128.6, 129.3, 135.9, 142.3, 144.2, 144.5, 145.7, 145.8, and 146.2. 
The wet cake from above was diluted with 125 g of methanol and 2.9 g (0.013 
mol) of 25 percent by weight sodium methoxide in methanol was added with 
stirring at ambient temperature in several portions. The mixture 
thickened. After 1.5 hour a solution of 2.4 mL (.0.15 mol) of 6.25N 
aqueous hydrochloric acid in 125 mL of water was added with stirring and 
cooling by means of an ice bath. The mixture was cooled to about 5.degree. 
C., diluted with 80 g of water, vacuum filtered to recover the insoluble 
solids, and dried under reduced pressure to obtain 40.3 g (95 percent of 
theory) of the title compound as a colorless solid. This compound was 
identical spectroscopically and by quantitative HPLC with the compound 
reported in U.S. Pat. No. 5,163,995. 
NMR data (DMSO-d6) .delta.: .sup.1 H: 4.17 (s, 3H), 4.51 (s, 2H), 7.3 (m, 
3H), 7.45 (d(J=7.2 Hz), 2H), and 8.13 d(J=4.0 Hz), 1H; .sup.13 C: 34.8, 
56.4, 127.3,128.4, 128.6, 128.8, 136.7, 141.4, 144.7, 145.4, 147.1, 147.5, 
and 161.6. 
10. Preparation of 
8-Fluoro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione. 
A mixture of 10.01 g (0.050 mol) of 
8-fluoro-5-methoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione in 8.6 g 
of methanol was prepared and cooled with an ice water bath. Sodium 
methoxide in methanol (32.4 g of 25 percent, 0.15 mol) was added under 
nitrogen with stirring and cooling. After 2.5 hours, 25.6 mL of ice cold 
6.25N aqueous hydrochloric acid was added with stirring to the thick 
slurry obtained. The resulting mixture was diluted with a little water and 
the solids were recovered by vacuum filtration and dried under reduced 
pressure to obtain 8.26 g (83 percent of theory) of the title compound as 
a colorless powder. The compound melts at 155.degree.-160.degree. C. and 
then resolidifies and does not remelt up to 230.degree. C. 
NMR data (CD.sub.3 CN) .delta.: .sup.1 H: 2.5-3.5 (br s, 1H), 4.21 (s, 3H), 
7.92 (d(J=2.1 Hz), 1H); .sup.13 C: 57.4, 118.2, 129.2, 129.5, 43.0, 146.4, 
146.7, 148.7, 149.1, and 163.8. 
11. Preparation of 5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-2(3H) 
-thione 
A mixture of 5.8 g (26 mmol) of 
5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione in 50 mL of 
absolute ethanol was prepared and to this was added at 0.degree. C. with 
vigorous stirring and cooling 12.2 mL (33 mmol) of 21 weight percent 
sodium ethoxide in ethanol. A mildly exothermic reaction took place and 
the mixture changed from a suspension to a plum colored solution. The 
mixture was stirred at below 10.degree. C. for 2.25 hours to complete the 
reaction. It was then acidified with 25 mL of 1.25N hydrochloric acid, 
stirred at -10.degree. C. for 30 min, and filtered to recover the 
precipitate that formed. The precipitate was washed with 10 mL of cold 
water and dried to obtain 3.3 g (60 percent of theory) of the title 
compound of 98 percent purity. A second crop amounting to 1.7 g of 60 
percent purity material (19 percent of theory) was obtained from the 
filtrate. The title compound melts at 83.5.degree. C. to 86.5.degree. C. 
and is a white solid. 
NMR data (CDCl.sub.3) .delta.: .sup.1 H: 1.58 (t, 3H), 4.52 (s, 2H), 4,75 
(q, 2H), 7.28 (m, 3H), 7.45 (d, 2H). 
The identity of the compound was further demonstrated by converting it into 
2-benzylthio-5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine, melting at 
78.degree.-82.degree. C., by treatment with benzyl chloride. 
12. Preparation of 
8-Chloro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione 
8-Chloro-5-methoxy-1,2,4-triazolo[4,3-c]-pyrimidine-3(2H)-thione (0.215 g, 
1.00 mmol) was mixed with 2.0 g of dry methanol and to this mixture was 
added, in increments with stirring at ambient temperature, 0.26 g (1.2 
mmol) of commercial 25 percent sodium methoxide in methanol. After a 
35-min reaction period, the mixture was acidified with aqueous 
hydrochloric acid and diluted with water. The precipitate that formed was 
recovered by filtration and dried to obtain 0.168 g of the title compound 
in 97 percent purity as determined by HPLC (76 percent of theory) as a 
cream colored solid. The compound can be recrystallized from a mixture of 
methanol and water; it decomposes, but does not melt up to 250.degree. C. 
NMR data (CDCl.sub.3) .delta.: .sup.1 H: 4.28 (s, 3H), 7.93 (s, 1H) over 14 
(not observed); .sup.13 C: 56.0, 112.0, 142.1, 148.0, 153.5, and 163.0. 
The identity of the product was further demonstrated by converting it into 
2-benzylthio-8-chloro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine, a 
compound known in U.S. Pat. No. 5,163,995, by treatment with benzyl 
chloride. 
13. Preparation of 
3-Benzylthio-5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-c]pyrimidine from 
2-Ethoxy-4-fluoro-6--hydrazinopyrimidine 
A 1.74 g (10 mmol) sample of 2-ethoxy-4-fluoro-6-hydrazinopyrimidine was 
dissolved in 20 mL of absolute ethanol and 2.84 g (37 mmol) of carbon 
disulfide and 3.20 g (10 mmol) of 21 percent by weight sodium ethoxide 
were added. The mixture was heated at reflux with stirring for 3 hours and 
then was cooled by adding 20 mL of ice water. The mixture was then 
acidified to a pH of about 2 by adding 2 mL of 6.25N hydrochloric acid 
diluted to 8 mL with water. The yellow precipitate that formed was 
recovered by filtration, washed with water, and dried to obtain 0.85 g (40 
percent of theory) of 
5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione. The proton 
and carbon NMR spectra of this material were consistent with its assigned 
structure. 
A 0.22 g portion of the product obtained above was dissoved in 2.5 g of 
absolute ethanol and 0.18 g of benzyl chloride and then 0,114 g of 
triethylamine were added with stirring at ambient temperature. When the 
starting material disappeared as determined by HPLC, the reaction mixture 
was added slowly to an excess of dilute aqueous hydrochloric acid. The 
beige crystals that formed were recovered by filtration, washed with 
water, and dried to obtain 0.27 g of 
3-benzylthio-5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-c]pyrimidine as a solid. 
The proton and carbon NMR spectra of this material were consistent with 
its assigned structure. 
14. Preparation of 
2-Benzylthio-5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine by 
Isomerization of 
3-benzylthio-5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-c]pyrimidine 
A solution of sodium ethoxide in ethanol was obtained by dissolving one 
drop (15 mg, 0.05 mmol) of 21 percent by weight sodium ethoxide in enough 
ethanol to make 0.17 g total. Ten drops of this were then added to 0.15 g 
of 3-benzylthio-5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-c]pyrimidine in 4 g 
of absolute ethanol. The cloudy mixture became clear and after 1 hour 
sufficient water was added to cause the product to precipitate. The 
precipitate was recovered by filtration, washed with water, and dried to 
obtain 0.14 g (93 percent of theory) of the title compound as a white 
solid melting at 83.5.degree.-84.degree. C. 
15. Preparation of 2,2'-Dithiobis(8-fluoro-5-methoxy[1,2,4]triazolo[1,5-c 
]pyrimidine) 
A heterogeneous mixture composed of 76.0 g (0.380 mol) of 
8-fluoro-5-methoxy[1,2,4]triazolo[1,5-c ]pyrimidine-2(3H)-thione and 400 g 
of methanol at 24.degree. C. was prepared and 45.3 g (0.400 mol) of ice 
cold 30 percent by weight hydrogen peroxide solution was added with 
stirring. An exothermic reaction took place raising the temperature to 
43.degree. C. The mixture was allowed to react for about 75 min and then 
another 13.0 g (0,115 mol) of ice cold 30 percent by weight hydrogen 
peroxide solution was added with stirring. The mixture was allowed to 
react for another 30 m in and then the solids present were recovered by 
vacuum filtration. These solids were dried and were then slurried with 
methanol. The slurry was heated to reflux, cooled to 35.degree.-45.degree. 
C., and filtered to recover the insoluble solids. The solids were dried 
under reduced pressure at 40.degree. C. to obtain 61.9 g of the title 
compound (80 percent of theory) as an off-white solid. The compound is a 
white powder melting at 201.degree.-208.degree. C. (dec.). 
NMR data (DMSO-d6) .delta.: .sup.1 H: 4.16 (s, 3H), 8.21 (d(J=2.1 Hz), 1H). 
16. Preparation of 
2,2'-Dithiobis(5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine) 
A solution of 2.9 g (13.5 mmol) of 
5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-2(3H) -thione in 30 mL 
of acetonitrile was prepared and 0.80 mL (7.8 mmol) of 30 percent hydrogen 
peroxide was added at ambient temperature with stirring under nitrogen. 
The temperature rose from 21.degree. to 34.degree. C. The mixture was 
allowed to react for about 1 hour and then 15 mL of water was added and 
the mixture was cooled to -5.degree. C. The precipitate that formed was 
recovered by vacuum filtration, washed with two 10 mL portions of a 1:1 
mixture of water and acetonitrile at 5.degree. C., and dried to obtain 2.7 
g (93 percent of theory) of the title compound as a light beige powder 
melting at 215.degree.-216.degree. C. 
Elemental Analysis for C.sub.14 H.sub.12 F.sub.2 N.sub.8 O.sub.2 S.sub.2 : 
Calc.: %C, 39.4; %H, 2.83; %N, 26.3 Found: %C, 39.6; %H, 2.75; %N, 25.9. 
17. Preparation of 
2,2'-Dithiobis(5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine) From 
5-Ethoxy-7-fluoro-1,2,4-triazolo[4,3-c]pyrimidine-3(2H-thione 
Procedure A: A mixture of 167 g (0.76 mol) of 
5-ethoxy-7-fluoro[1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione and 1.67 L 
of toluene denatured absolute ethanol was prepared and to this was added 
331 mL (0.887 mol) of 21 percent sodium ethoxide in ethanol at 0.degree. 
C. with vigorous stirring and cooling. The reaction proceeded with a small 
exotherm and the heterogeneous light beige mixture became a plum colored 
solution. This solution was maintained at a temperature of between 
5.degree. C. and 10.degree. C. for 2.25 hours and was then acidified with 
150 mL of 6.25N hydrochloric acid diluted with 685 mL of water. The 
resulting mixture was allowed to warm to ambient temperature (23.degree. 
C.) and then 43.4 mL of 30 percent aqueous hydrogen peroxide (0.43 mole) 
was added with stirring. The temperature rose to 33.degree. C. and after 
30 min all of the thione starting material was consumed as determined by 
HPLC. The mixture was cooled to 20.degree. C. and the title compound, 
which precipitated, was recovered by filtration and washed at 5.degree. C. 
with two 600 mL portions of water and then 350 mL of 50 percent aqueous 
ethanol. The white solid obtained was dried under reduced pressure at 
35.degree. C. to obtain 154 g of the title compound of about 90 percent 
purity as estimated by HPLC (86 percent of theory). Procedure B: A solid 
mixture that is 68 percent pure by analysis and contains 1.89 parts of 
5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione along with 
sulfur, less than 2 percent water, and some acetonitrile is diluted with 
8.61 parts of absolute ethanol and the mixture is cooled to 10.degree. C. 
A 21 percent sodium ethoxide by weight in ethanol solution (3.21 parts) is 
added with stirring and, after a few minutes, the mixture is filtered to 
remove the sulfur, retaining the filtrate. The sulfur is washed with 0.484 
parts of absolute ethanol and the filtered wash ethanol is added to the 
filtrate. The filtrate mixture is allowed to react at 10.degree. C. until 
isomerization is complete. The mixture is then acidified with 1.16 parts 
of 37 percent aqueous hydrochloric acid with stirring and cooling to keep 
the temperature below 25.degree. C. A 30 percent by weight solution of 
hydrogen peroxide in water (0.602 parts) is added slowly with stirring and 
cooling to keep the temperature below 30.degree. C. and the mixture is 
stirred an additional 30 min after the addition is complete. The 
precipitate that forms is recovered by filtration in a reduced pressure 
apparatus and is washed with 3.40 parts of ethanol and 8.70 parts of water 
to obtain the title compound as a water-wet solid. 
18. Preparation of 
2,2'-Dithiobis(5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine) From 
4,6-Difluoro-2-ethoxypyrimidine 
A mixture consisting of 32.7 g (0.202 mol) of 
2-ethoxy-4,6-difluoroethoxypyrimidine, 59 g of acetonitrile, and 36 g of 
water was prepared in a reaction vessel and the mixture was stirred under 
nitrogen and cooled to about 5.degree. C. To this was added 21.3 g (0.208 
mol) of triethylamine and then 10.6 g (0.208 mol) of hydrazine monohydrate 
with stirring and cooling at a rate that maintained the reaction 
temperature at less than 15.degree. C. After all of the hydrazine 
monohydrate had been added and the exotherm had subsided, the mixture was 
allowed to warm to ambient temperature to complete the reaction. A 
solution containing about 32.7 g (0.202 mol) of 
2-ethoxy-4-fluoro-6-hydrazinopyrimidine in approximately 95 g of aqueous 
acetonitrile was obtained. 
The solution of 2-ethoxy-4-fluoro-6-hydrazinopyrimidine in aqueous 
acetonitrile obtained above was placed into a reaction vessel and 23.1 g 
(0.303 mol) of carbon disulfide was added with stirring under nitrogen. 
After about 15 min, 23.8 g (0.210 mol) of 30 percent by weight aqueous 
hydrogen peroxide was added with stirring and cooling to hold the 
temperature at about 25.degree.-30.degree. C. A precipitate formed. The 
mixture was allowed to react for about 1 hour and was then cooled to 
0.degree. C. It was then filtered to recover the precipitate. The 
precipitate was washed first with two 75 mL portions of cold water to 
remove impurities and then with two 50 mL portions of cold acetonitrile to 
remove water. The 48.7 g of solid material obtained was determined to be 
71 percent 5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione 
by HPLC (35 g, 80 percent of theory) and to contain less than 2 percent 
water by Karl Fischer titration. Elemental sulfur by-product was the major 
contaminant. 
The 48.7 g (0.16 mol) of 
5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione as a 71 
percent mixture with sulfur and acetonitrile obtained above was combined 
with 150 g of dry ethanol and the mixture was cooled to about 0.degree. C. 
To this was added 67.7 g (0.21 mol) of 21 percent sodium ethoxide in 
ethanol with cooling and stirring such that the temperature was maintained 
between 5.degree. and 15.degree. C. The pH of the mixture was about 12. 
The mixture was filtered to remove the solid, insoluble sulfur and it was 
washed with 20 g of dry ethanol. The filtrate (including the wash ethanol) 
was allowed to react at about 7.degree. C. for about another 2 hours and 
then 21.7 g (0.22 mol) of concentrated hydrochloric acid was added to 
obtain 5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione as a 
thin slurry of a light beige solid in ethanol. 
The mixture of 
5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione in ethanol 
obtained above was treated with 22.6 g (0.199 mol) of 30 percent hydrogen 
peroxide with stirring at ambient temperature. There was a mild exotherm. 
After a 40 min reaction period, the resulting mixture was filtered to 
recover the precipitate. This was washed with two 100 mL portions of 
ethanol and two 100 mL portions of water and dried at 37.degree. C. under 
reduced pressure to obtain 30.9 g (65 percent of theory from 
2-ethoxy-4,6-difluoropyrimidine) of the title compound as a light tan 
solid of 90 percent purity. 
19. Preparation of 
2-Chlorosulfonyl-5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine From 
2,2'-Dithiobis(5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine) 
A mixture containing 53.3 g of 88 percent purity (0.11 mol) of 
2,2'-dithiobis(5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine), 483 g 
of dichloromethane, and 12.0 g of water was prepared and cooled to about 
5.degree. C. Chlorine (42.5 g, 0.60 mol) was sparged into this mixture 
with cooling and stirring over a 2.5-hour period so that the temperature 
did not rise above about 15.degree. C. Another 37.1 g of water was added 
during the course of the chlorine addition. The solids originally present 
became thicker at first and then essentially everything went into 
solution. The resulting mixture was diluted with about 200 mL of water and 
the phases were separated. The gold colored organic phase was washed with 
three 400 mL portions of water, dried over magnesium sulfate, filtered, 
and concentrated by evaporation under reduced pressure with a bath 
temperature up to 38.degree. C. The title compound was contained in the 
residue, which amounted to 59.5 g (96 percent of theory) and was a waxy 
yellow-gold solid. A 12.66 g portion of this was purified by dissolving it 
in about 30 mL of dichloromethane, adding about 30 mL of hexane, and 
cooling. The precipitate that formed was recovered by filtration, dried to 
obtain 8.15 g of the title compound as a white solid. A 3.16 g second crop 
was also obtained. The product was identified spectroscopically to be the 
same compound as that reported in U.S. Pat. No. 5,163,995. 
20. Preparation of 
2-chlorosulfonyl-5-ethoxy-7-fluoro[2,4]triazolo[1,5-c]pyrimidine From 
5-Ethoxy-7-fluoro[ 1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione 
A mixture consisting of 3.7 g (17.3 mmol) of 
5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione, 45 mL of 
dichloromethane, and 15 mL of water was placed in a three necked flask 
equipped with a mechanical stirrer, an outlet tube connected to a caustic 
scrubber, a chlorine inlet sparge tube, and a cooling bath. Compete 
solution was not attained. Chlorine was sparged into the solution at 
0.degree. C. with stirring and cooling until 7.0 g, (99 mmol) was added. 
The solids all dissolved. The aqueous and organic layers were separated 
and the organic layer was dried over magnesium sulfate and concentrated by 
evaporation under reduced pressure to obtain the title compound as a 
residue. The recovered product, which was an orange solid of approximately 
88 percent purity, amounted to 3.6 g (75 percent of theory). The compound 
was identified spectroscopically to be the same as that reported in U.S. 
Pat. No. 5,163,995.