Process for the production of 1,2,4-triazin-5-one derivatives

1,2,4-triazin-5-one compounds of the general formula (I) ##STR1## where R is ##STR2## are prepared by reacting a compound of general formula (II) ##STR3## in which R is defined above with either (a) a tertiary alcohol of general formula (III) EQU HO--R' (III) PA0 in which R' is a t-alkyl group having 4 to 18 carbon atoms, especially t-amyl or t-octyl or preferably t-butyl or PA0 (b) an alkene of general formula (IV) ##STR4## in which R.sub.1 and R.sub.2 are the same or different and are hydrogen or an alkyl group and R.sub.3 and R.sub.4 are the same or different and wherein the alkyl groups in each case can be 1 to 15 carbon atoms and wherein preferably R.sub.1 and R.sub.2 are hydrogen and R.sub.3 and R.sub.4 each are methyl to form an .alpha.-ketocarboxylic acid amide of general formula (V) ##STR5## and this, in a given case after previous saponification to the free acid, condensed with thiocarbohydrazide ##STR6## to form a 1,2,4-triazin-5-one compound of general formula (VI) ##STR7## and then the mercapto group is methylated.

BACKGROUND OF THE INVENTION 
The object of the invention is to develop a new process for the production 
of 3-methylmercapto-4-amino-6-t-butyl-1,2,4-triazin-5-one, which is a 
known herbicide, and for the production of 
3-methylmercapto-4-amino-6-(1-methyl-cyclopropyl)-1,2,4-triazin-5-one 
which has not previously been described and likewise is effective as a 
selective herbicide. The above-mentioned 6-(1-methyl-cyclopropyl) compound 
can be used in the same way and against the same plants as the known 
6-t-butyl compound also mentioned above. 
The 3-methylmercapto-4-amino-6-t-butyl-1,2,4-triazin-5-one can be produced 
for example according to the process described in German OS No. 2,165,554 
by reaction of pivaloyl chloride with an isonitrile, the imidchloride 
formed hydrolyzed to an .alpha.-ketocarboxylic acid amide and the amide 
further reacted with thiocarbohydrazide in a polar solvent, in a given 
case in the presence of an acid catalyst. The disadvantage of this process 
is that it goes circuitously by way of the very ill-smelling and very 
expensive isonitriles. Besides the 3-mercapto compound can only be 
obtained in yield of 60% to 79%. 
The 1-methyl-cyclopropyl compound set forth above can be used as a 
herbicide in the manner taught in German OS No. 2,165,554. 
SUMMARY OF THE INVENTION 
It has now been found that 1,2,4-triazin-5-one compounds of the general 
formula (I) 
##STR8## 
where R is 
##STR9## 
are prepared by reacting a compound of general formula (II) 
##STR10## 
in which R is as defined above with either 
(a) a tertiary alcohol of general formula (III) 
EQU HO--R' (III) 
in which R' is a t-alkyl group having 4 to 18 carbon atoms, especially 
t-amyl or t-octyl or preferably t-butyl or 
(b) an alkene of general formula (IV) 
##STR11## 
in which R.sub.1 and R.sub.2 are the same or different and are hydrogen or 
an alkyl group and R.sub.3 and R.sub.4 are the same or different and 
wherein the alkyl groups in each case can be 1 to 15 carbon atoms and 
wherein preferably R.sub.1 and R.sub.2 are hydrogen and R.sub.3 and 
R.sub.4 each are methyl to form an .alpha.-ketocarboxylic acid amide of 
general formula (V) 
##STR12## 
and this, in a given case after previous saponification to the free acid, 
condensed with thiocarbohydrazide 
##STR13## 
to form a 1,2,4-triazin-5-one compound of general formula (VI) 
##STR14## 
and then the mercapto group is methylated. This procedure avoids the 
disadvantages of the procedure of German OS No. 2,165,554. 
The reaction of the acyl cyanide of general formula (II) with the tertiary 
alcohol of general formula (III) or the alkene of general formula (IV) 
takes place under the conditions of the so-called "Ritter Reaction" of 
"Graf Ritter Reaction" (J.A.C.S. Volume 70, pages 4045 et seq. (1948); 
J.A.C.S. Volume 70, pages 4048 et seq. (1948); Methodicum Chemicum, Volume 
6 (1974)) page 710. It is completely surprising that the quite unstable 
acyl cyanides are able to carry over this reaction since it was much more 
to be expected that as a result of the acid treatment there would be a 
splitting off of hydrocyanic acid. 
The reaction can be carried out in the absence of a solvent, but is 
suitably undertaken in the presence of an organic solvent. Glacial acetic 
acid and dichloromethane are particularly suitable. Other useful solvents 
include, for example, higher ethers such as dibutyl ether, diisopropyl 
ether, dipropyl ether or diamyl ether or acetic anhydride. 
The reaction temperature can be varied within wide limits. The preferred 
temperatures are between -20.degree. C. and +50.degree. C. 
Suitable the reactants are added in such amounts that for each mole of acyl 
cyanide there is employed an overstoichiometrical amount of alcohol or 
alkene. For example, there can be used per mole of acyl cyanide 1 to 20 
moles, preferably 1.5 to 2 moles, of alcohol or alkene. 
The acid is also suitably used in a slight excess amount. For example, 
there can be used per mole of acyl cyanide 1 to 10 moles, preferably 1.1 
to 1.5 moles, of acid. 
As acid there is preferably used sulfuric acid. However, there can be used 
other sulfonic acids, e.g., organic sulfonic acids such as benzenesulfonic 
acid, p-toluene sulfonic acid, methanesulfonic acid, ethanesulfonic acid, 
etc. 
As alcohols of formula III, there can be used for example t-butanol, 
t-octanol, t-octadecanol, t-dodecanol, t-pentanol, t-hexanol, etc. 
As alkenes of formula IV, there can be used particularly 2-methylbutene-2 
and diisobutylene and preferably isobutylene. Other alkenes which can be 
used include 2-methyl-heptadecene-1, 2-ethyl-hexene-1, 3-methyl-hexene-2, 
2-methyl-heptene-2, etc. 
After the hydrolysis of the reaction mixture, the ketocarboxylic acid amide 
can be intermediately isolated by known procedures, for example, by 
crystallization or extraction with subsequent crystallization or 
distillation. 
The acyl cyanide of formula II can be prepared in known manner from the 
corresponding carboxylic acid halide by reaction with a metal cyanide, 
e.g., cuprous cyanide (Hurd J.A.C.S. Volume 66, pages 2013-2014 (1944), 
German patent application No. P 27 08 183.0 and related Klenk U.S. 
application Ser. No. 802,944, filed June 2, 1977 and now U.S. Pat. No. 
4,108,877, German patent application No. P 27 08 182.9 and related Klenk 
U.S. application Ser. No. 802,942, filed June 2, 1977 and now U.S. Pat. 
No. 4,108,875. The entire disclosure of Hurd and the two Klenk U.S. 
applications are hereby incorporated by reference and relied upon.) 
The .alpha.-ketocarboxylic acid-t-alkylamide of formula V recovered in the 
first step of the process of the invention can be supplied as such 
directly to the further reaction with thiocarbohydrazide in the presence 
of a polar solvent such as an alcohol, e.g., methyl alcohol, ethyl 
alcohol, isopropyl alcohol or butyl alcohol, water, dimethyl sulfoxide, 
dimethyl formamide, etc., or mixtures of these solvents and, in a given 
case, in the presence of an acid catalyst, particularly hydrochloric acid 
or sulfuric acid, in an amount which is at least equivalent to the amide. 
Thus, the thiocarbohydrazide can be used in an amount of 1 to 2 moles per 
mole of the .alpha.-ketocarboxylic acid-t-alkylamide. In this reaction, 
the temperature can be held between 0.degree. C. and the boiling point of 
the solvent. 
However, it is also possible to first convert the .alpha.-ketocarboxylic 
acid-t-alkylamide of formula V to the free .alpha.-ketocarboxylic acid 
which procedure can take place by known methods, and then the ring closure 
with the thiocarbohydrazide carried out by the methods of A. Dornow (Ber. 
Volume 97, pages 2173-79 (1964)). 
In both cases, the methylation of the sulfur atom is then carried out in 
known manner, for example, by treating with a methylating agent such as 
methyl iodide, methyl bromide or dimethyl sulfate in an alkaline medium, 
e.g., using sodium hydroxide or potassium hydroxide. 
The process can comprise, consist essentially of or consist of the steps 
set forth with the materials set forth. 
Unless otherwise indicated, all parts and percentages are by weight.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
Example 1 
##STR15## 
111 grams (1.0 mole) of pivaloyl cyanide were added to a mixture of 148 
grams (2.0 moles) of t-butanol and 50 ml of methylene chloride. Then there 
were dropped in with stirring at 0.degree.-5.degree. C. 150 grams of 98% 
sulfuric acid and then the temperature increased to 20.degree. C. Stirring 
was continued for 4 hours, the mixture poured on 400 grams of ice and 
stirred for 30 minutes. Then the mixture was diluted with 300 ml of 
methylene chloride, the organic phase separated of and the methylene 
chloride solution evaporated. There remained a white, crystalline residue 
which was washed with about 500 ml of water on a suction filter. The 
residue was then dried. There remained 133 grams (72%) of trimethyl 
pyruvic acid-N-t-butylamide having a melting point of 
63.degree.-65.degree. C. 
Analysis Calc: C 64.38; H 10.34; N 7.56. Found: 64.59; 10.44; 7.32. 
##STR16## 
111 grams (1.0 mole) of pivaloyl cyanide were added to a mixture of 150 ml 
of glacial acetic acid and 150 grams of 100% sulfuric acid. Then there 
were led in with stirring at 5.degree.-10.degree. C. during 1 hour 112 
grams (2.0 moles) of isobutylene. Then the temperature was increased to 
20.degree. C. and stirring continued for 2 hours. Then there were dropped 
in with slight cooling an about 5 normal aqueous NaOH solution until a pH 
of 8 was reached. Stirring was continued for a further 30 minutes and the 
precipitated trimethyl pyruvic acid-N-t-butylamide was filtered off. There 
remained behind 172 grams (93% yield based on the acid cyanide added). The 
amide had a melting point of 63.degree.-65.degree. C. and is identical 
with the amide described in (a). 
##STR17## 
185 grams of trimethyl pyruvic acid-N-t-butylamide were heated in 1 liter 
of 5 normal HCl for 10 hours under reflux. After cooling the product was 
extracted by shaking with methylene chloride and then the methylene 
chloride phase was extracted with dilute aqueous NaOH solution. The 
alkaline aqueous solution was then adjusted to a pH of 1 with concentrated 
HCl and then extracted by shaking with ethyl acetate. The ethyl acetate 
extract was evaporated. There remained behind 97.5 grams (75% of theory) 
of trimethyl pyruvic acid as a light oil which after some time began to 
crystallize. 
##STR18## 
53 grams (0.5 mole) of thiocarbohydrazide in 600 ml of water were heated to 
boiling. Under stirring there were dropped in during about 2 hours 65 
grams (0.5 mole) of the trimethyl pyruvic acid obtained in (c) in ethanol. 
Then heating was continued for a further 4 hours under reflux. The mixture 
was allowed to cool and the crystals removed with suction. Thus there were 
isolated after drying 94 grams (94% of theory of 
3-mercapto-4-amino-6-t-butyl-1,2,4-triazin-5-one) (M.P. 
212.degree.-214.degree. C.). 
(e) Methylation of the 3-mercapto-4-amino-6-t-butyl-1,2,4-triazin-5-one 
100 grams of the compound obtained according to (d) were dissolved in a 
mixture of 250 ml of 2 normal NaOH and 250 ml of methanol and then treated 
with 75 grams of methyl iodide. Then the mixture was stirred for 4 more 
hours at 20.degree. C. The reaction product which crystallized out was 
filtered off with suction, dried and recrystallized from benzene. There 
were obtained 92 grams (80% of theory) of 
3-methylmercapto-4-amino-6-t-butyl-1,2,4-triazin-5-one having a melting 
point of 126.degree. C. 
Example 2 
##STR19## 
There were dropped into 53 grams (0.5 mole) of thiocarbohydrazide in 500 ml 
of 1 normal HCl with stirring and heating to reflux 92.5 grams (0.5 mole) 
of the trimethyl pyruvic acid-t-butylamide produced in accordance with 
Example 1(a) in 200 ml of ethanol. Then heating was continued for 8 hours. 
After cooling the mixture was diluted with 1 liter of water and the 
crystals removed with suction. There were isolated 72 grams (72% of 
theory) of the desired triazinone (M.P. 209.degree.-213.degree. C.). The 
methylation was carried out as described in Example 1(e). 
Example 3 
(a) Production of (1-Methyl-cyclopropyl)-glyoxyltert.-butylamide 
109 grams of (1-methyl-cyclopropyl)-carboxylic acid cyanide (1 mole) were 
added to a mixture of 130 grams of t-butanol and 130 ml of methylene 
chloride. Then there were dropped in with stirring at 0.degree. to 
5.degree. C. 100 grams of 98% sulfuric acid, the temperature increased to 
20.degree. C. and stirring continued for 4 hours. Then there were added 18 
ml of water and stirring carried out again for 30 minutes. The mixture was 
diluted with 500 ml of methylene chloride and adjusted with cooling with 
aqueous NaOH to a pH of 6. The methylene chloride solution was then 
evaporated. There remained 181 grams (98.9% of theory) of 
(1-methyl-cyclopropyl)-glyoxyl-tert.-butylamide, M.P. 80.degree. C. 
Analysis Calculated: C 65.5; H 9.3; N 7.65. Found: 65.2; 9.4; 7.45. 
(b) Production of 
4-Amino-6-(1-methyl-cyclopropyl)-3-mercapto-1,2,4-triazin-5-one 
183 grams of (1-methyl-cyclopropyl)-glyoxalic acid-tert.-butylamide and 112 
grams of thiocarbohydrazide were added to a mixture of 1 liter of 1 normal 
HCl and 1 liter of ethanol. The mixture was boiled under reflux for 8 
hours, cooled, diluted with 2 liters of water and the crystals filtered 
off with suction. There were obtained white crystals with a yellow luster 
which were dried. 
Amount: 152.6 grams (77.1% of theory) 
M.P. 137.degree. to 138.degree. C. 
Analysis Calculated: C 42.4; H 5.05; N 28.3; S 16.16. Found: 42.2; 5.1; 
28.1; 16.1. 
(c) Methylation of the 
4-Amino-6-(1-methyl-cyclopropyl)-3-methylthio-1,2,4-triazin-5-one 
198 grams of the compound obtained according to (b) were dissolved in 500 
ml of 2 normal NaOH and treated with 500 ml of methane and 150 grams of 
methyl iodide. The mixture was stirred for 6 hours at 20.degree. to 
30.degree. C. The crystals formed were filtered off with suction, washed 
and dried. There are obtained 174.5 grams of final product (dried in a 
vacuum at 40.degree. C.), white crystals, M.P. 115.degree. to 116.degree. 
C. 
Yield: 82.3% of theory. 
______________________________________ 
Analysis Calculated 
C 45.3 H 5.7 N 26.4 
S 15.1 
(Molecular 
Found 45.3 5.8 26.1 15.3 
weight 212) 
______________________________________