4-Amino-6-(2'carboxyethyl)-3-methylthio-1,2,4-triazin-5(4H)-one is prepared by reaction of methylthiocarbonohydrazide iodide with .alpha.-ketoglutaric acid for use as a previously unknown compound in structure-activity relationship studies of herbicides and plant growth regulators and as an intermediate in the preparation of new 1,2,4-triazin-5(4H)-ones.

BACKGROUND 
6-Alkyl- and aryl-4-amino-3-methylthio-1,2,4-triazin-5(4H)-ones are known 
(Dornow, Chem. Ber. 1964, 2173; U.S. Pat. Nos. 3,671,523; 3,961,936; 
3,966,715; and 4,113,767) and one member of the class; i.e., the 
6-tert.-butyl compound, is the widely used herbicide, metribuzin (Merck 
Index No. 6027). A variety of substituted types are known which possess 
herbicidal activity. 6-Carboxy and 
6-(.delta.-carboxyalkyl)-3-mercapto-4-amino-1,2,4-triazin-5(4H)-ones are 
described in my copending application Ser. No. 06/238,480 filed 02/26/81. 
These 6-carboxyalkyl types are advantageously obtained from .alpha.-keto 
dicarboxylic acids thus avoiding the costly economic and environmental 
problems encountered in the manufacture of the 6-tert.-butyl derivative, 
metribuzin. These problems have been stated in detail in U.S. Pat. No. 
4,113,767, which describes a sulfur dichloride chlorination process for 
the preparation of trimethylpyruvic acid, the primary starting material - 
a process which is a source of contaminating possibilities such as the 
chlorinated by-products resulting from sulfur dichloride chlorination of 
the tert.-butyl group. .alpha.-Ketoglutaric acid, the starting material 
for the preparation of the 6-(2'-carboxyethyl)-triazinone of the present 
invention is available from environmentally acceptable and economically 
advantageous fermentation processes (U.S. Pat. Nos. 2,443,919; 2,841,616). 
3-Methylthio-triazin-5(4H)-ones have been previously and customarily 
prepared by reaction of a strongly alkaline solution of the 
6-mercaptotriazinone with methyl iodide (U.S. Pat. Nos. 4,113,767; 
4,036,622). There is no known previous reference to the use of 
S-methylthiocarbonohydrazide iodide, the preparation which is given in J. 
Org. Chem. 19, 1231 (1954), for the preparation of 
3-methylthio-4-amino-6-substituted-1,2,4-triazin-5(4H)-ones of any type.

Description of the Invention 
4-Amino-6-(2'-carboxyethyl)-3-methylthio-1,2,4-triazin-5(4H)-one is 
prepared from S-methylthiocarbonohydrazide and .alpha.-ketoglutaric acid. 
The S-methylthiocarbonohydrazide in the form of a quaternary salt is 
dissolved in a suitable solvent at slightly elevated temperature and mixed 
at once with an approximately equivalent amount of the .alpha.-keto 
dicarboxylic acid to form a warm solution from which the product 
precipitates in good yield and in essentially pure format once or on 
standing and cooling. The S-methylthiocarbonohydrazide is used in the form 
of its iodide salt prepared as described in J. Org. Chem. 19, 1231 (1954). 
The solvent used in the reaction is water or alcohol-water. The use of 
water alcohol mixtures increases the yield by decreasing the solubility of 
the product and facilitating its isolation. The amount of alcohol used is 
selected as less than that at which ready solution of the reactants can be 
obtained. 
The reaction is run at temperatures of 50.degree.-100.degree. C. preferably 
at 60.degree.-70.degree. C. At lower temperatures the reactants are not 
readily soluble and thus are less available for complete and prompt 
reaction. At higher temperature the .alpha.-keto acid undergoes slight 
decarboxylation with resultant lowering of the yield of product. The 
reaction at 60.degree.-70.degree. C. is rapid and immediately on or within 
minutes after mixing the product begins to precipitate. Additional time is 
allowed for completion of the reaction. The order of mixing of the 
reactants is not critical but it is advantageous to first dissolve the 
S-methylthiocarbonohydrazide and then dissolve the acid thus minimizing 
loss of acid through decarboxylation. 
The yield of product is enhanced by partial evaporation of the reaction 
mixture before or after separation of the initially precipitated product. 
The by-product hydrogen iodide can be recovered for reuse from the mother 
liquor--as methyl iodide. 
A remarkable feature of this invention is that it circumvents the usual 
procedure for the conversion of 3-mercaptotriazinones to their S-methyl 
derivatives. The usual and customary procedure utilizes the reaction of 
the mercaptotriazinone with methyl iodide in the presence of an equivalent 
amount of strong base; e.g., sodium methoxide or hydroxide in methanol or 
dimethylformamide. Such strongly alkaline conditions are inoperable for 
converting the mercapto-carboxy-triazinone to its S-methyl derivative. The 
acid must be neutralized to achieve the requisite alkalinity and the 
resultant carboxylate anion is readily decarboxylated or disruptive of the 
displacement reaction or has altered solubility characteristics making 
isolation of the product difficult. 
The product of the invention is isolated in an essentially pure form. It 
can, however, be further purified by washing with cold alcohol or ether, 
in which it is insoluble or by recrystallization from hot alcohol in which 
it is sparingly soluble or from hot alcohol with small amounts of added 
water. The product is acidic and can be titrated with standard base. 
Potentiometric titration shows a pronounced break at an equivalence point 
near pH 8.5 and a pH at half neutralization of about 5 indicating a 
pK.sub.a in the 5 range. 
The following examples illustrate the operation of the invention. 
EXAMPLE 1 
4-Amino-6-(2'-carboxyethyl)-3-methylthio-1,2,4-triazin-5(4H)-one. To 20 ml 
of water at 60.degree. C. is added 10.8 g (0.0435 moles) of 
S-methylthiocarbonohydrazide iodide. After stirring briefly to dissolve, 
6.0 g (0.04 moles) of .alpha.-ketoglutaric acid are added. The mixture is 
stirred to solution and warmed to 70.degree. C. within a few minutes and 
then allowed to cool. On standing, or more rapidly if seeded, at room 
temperature (or in an ice bath) crystals of the product separate. The 
crystals are collected, washed with cold water, then with cold ethanol, 
and dried to give 3.8 g of product, mp 203.degree.-204.degree. C. (dec.). 
The reaction mixture after filtration is diluted with an equal volume of 
ethanol to precipitate an additional 3 g of product. The total yield is 
74% of theory. The product is soluble in hot water, hot ethanol, hot 
methanol, and in 2 N sodium hyroxide. The analytical sample is dried at 
55.degree. C./0.5 mm. 
Anal. Calcd. for C.sub.7 H.sub.10 O.sub.3 N.sub.4 S: C, 36.52; H, 4.35; N, 
24.35; S, 13.91; neutr. equiv., 230. Found: C, 36.49; H, 4.60; N, 23.93; 
S, 13.88; neutr. equiv., 230.1 (potentiometric; to pH 8.5 at equivalence). 
EXAMPLE 2 
Example 1 is repeated using 1.25 N hydrochloric acid in place of the water. 
The product is obtained in low yield. 
EXAMPLE 3 
Example 1 is repeated with the temperature being raised to, at first 
90.degree. C., at which temperature gas evolution (CO.sub.2) is noted, and 
then to 95.degree. C. The yield of product is low and the product is 
contaminated with the carbohydrazone. 
The product of this invention is useful in further delineating the 
structure-activity relations amongst herbicides of the triazinone type and 
plant growth regulators of the auxin type. The product shows injury to 
several weed species in post-emergence tests. The product is also useful 
as an intermediate in the preparation of previously undesribed, novel 
herbicides and plant growth regulators via conversion of the carboxylic 
acid group.