JPS596316B2 - Substituted imidazo[1,5-d]-as-triazin-4(3H)-ones and thiones and their production method - Google Patents

Description

[Detailed description of the invention] The present invention relates to a novel organic compound.

Specifically, a novel substituted imidazo[1.5-d]-As-triazine-4(3H)- represented by the following formula (1)
It concerns ions and thiones. X here
is divalent z-ring or divalent sulfur; R1 is hydrogen, alkyl C
1-C3, bromine, chlorine, iodine, or bromoethyl; R
2 is hydrogen, alkyl C1-C4, cycloalkyl C3-
C6, methoxymethyl, bromine, benzyl, naphthyl, or phenyl (the phenyl is optionally substituted by chlorine, methyl, alkoxyC1-C, amino, dimethylamino or nitro); R3 is hydrogen,
alkyl C1-C3, allyl, or propargyl; and R4 is hydrogen or alkyl C1-C.

★G wing B day) HZ Ona r Irenotokame' eyes Lk66I
…÷YutoLzeY6Z monovalent oxygen; R, is methyl, bromine or chlorine; R, is cycloalkyl C3-C6, phenyl or m-tolyl; and both R3 and R4 are hydrogen (1 ) is a compound represented by the structural formula.
The present invention further relates to a novel organic compound which is an intermediate for producing the above-mentioned compound, and more specifically to a novel substituted 3-(4-imidazolylmethylene)carbazic acid [3-( 4-1mid residence 01y
1methylene) Carbazicacid] and esters of dithiocarbazic acid. R in the formula
1 and R2 are the same groups as above; R5 is the following or * R6 in the above formula is alkyl having up to 3 carbon atoms.

The novel intermediates exist in two tautomeric forms, which are equivalent for the purposes of the present invention: The novel compounds and novel intermediates of the present invention are generally white to yellow in color. It is obtained as a crystalline material with a characteristic melting point and absorption spectrum and is purified by recrystallization from common organic solvents such as methanol, ethanol, dimethylformamide, chloroform and the like.

They are fairly soluble in nonpolar organic solvents such as diphenyl ether and carbon tetrachloride, but relatively insoluble in water. R3 and R4 are both hydrogen (1
) compounds are easily produced by the following reaction method.

However, R is alkyl C1-C3, and R1 and R2 are the same as defined above. Oxidation of appropriately substituted 4-imidazole methanol () with concentrated nitric acid according to the above reaction scheme yields the corresponding 4-imidazole carboxaldehyde (). This oxidation is conveniently carried out by suspending or dissolving the starting material in about 1 ml to about 7 ml of concentrated nitric acid per 1f7 of starting material and heating the reaction mixture to steam bath temperature for 2 to 3 hours. Alternatively, the reaction mixture is first left at room temperature for 8-16 hours and then heated briefly (15-30 minutes) on a steam bath. Preferably, the reaction solution obtained is first diluted with water and then neutralized with any base such as caustic alkali, soda ash or concentrated aqueous ammonia. Trivial? The resulting product () is purified by separation, washing with water and recrystallization from common organic solvents such as ethyl acetate, ethanol and the like. Alternatively, 4-imidazole methanol ()
was oxidized with activated manganese dioxide in chloroform or tetrahydrofuran at room temperature to reflux temperature for 4 to 6 hours.
-Imidazole carboxaldehyde () can also be obtained. 4-imidazolecarboxaldehyde () can be treated with methyl or ethyl dithiocarbazate or 3-(4-imidazolylmethylene)dithiocarbazate () or by treatment with methyl or ethyl carbazate, respectively. It is easily converted to 3-(4-imidazolylmethylene)carbazate (V).

This condensation is conveniently carried out in a lower alkanol solvent containing a few drops of glacial acetic acid at temperatures between 25°C and 75°C, whereby the product () or (V) is formed almost instantaneously. f
Can be separated by filtration. 3-(4-imidazolylmethylene)dithiocarbazate () and 3-(4-
The cyclization of imidazolyl methylene)carbazate (V) is easily carried out by heating to 175°C to 275°C for 15 to 30 minutes in a nonpolar high-boiling organic solvent such as diphenyl ether, and the corresponding imidazolyl [1・5-
d]-As-triazine-4-(3H)-thiones ()
and imidazo[1,5-d]-As-triazine-4
(3H)-ones are obtained.

Compounds () in which R1 is chlorine or bromine are produced by chlorination or bromination of the corresponding compounds () in which R1 is hydrogen.

The halogenation is carried out by treating the starting material with chlorine or bromine in an inert solvent such as chloroform or carbon tetrachloride at steam bath temperature. Oxo compound (
) is converted to the thio compound ( ) by treatment with phosphorus pentasulfide in an inert solvent such as pyridine at reflux temperature. This method is particularly convenient when R is halogen.
The compound () in which R1 is iodo is prepared as follows: the aldehyde () in which R1 is hydrogen is converted to dimethyl acetal in methanol/hydrochloric acid, and the dimethyl acetal is hydrolyzed after iodization to form the corresponding iodoaldehyde ( a)
is obtained.

The iodoaldehyde (a) thus obtained is then converted into the desired compound () in which R1 is iodine according to the scheme described above.

Introduction of the R4 substituent into the imidaso A8-triazinone ring is accomplished by treatment of the aldehyde () with alkyl (C1-C3) magnesium bromide followed by the JOnes oxidation method.

The JOne4 conversion method was described by JOnes et al. C. S. (
1946) p. 39 and J. C. S. (1953), pages 457, 2548, and 3019. Upon oxidation of the secondary alcohol, ketone 01 is obtained. These reactions are explained below: where X is oxygen and R
The remaining synthetic steps to obtain the compound of formula (1), where 3 is hydrogen, involve carrying out the above method via cyclization of the carbazic acid ester of the ketone of formula () in diphenyl ether or the more suitable solvent 0-dichlorobenzene. It is achieved by doing so.

2(1) imidaso-As-triazinone compound (R
Alkylation of the 3-N position (3 is hydrogen) is carried out using conventional alkylating agents.

Another excellent method for the 3-N methylation of the specific imidaso-As-triazinone, namely 8-methyl-6-phenylimidazo[1,5-DlS-As-triazin-4(3H)-one, is to convert the latter triazinone into benzene. Alternatively, it is reacted with dimethylformamide, dimethyl acetal in an inert solvent such as toluene at a temperature of about 80°C to 90°C. The novel compounds of the present invention remain active as broad-spectrum herbicides, and some of them have antihypertensive activity at non-toxic doses and are useful as antihypertensive agents.

The present invention will be explained in more detail with reference to the following examples.

Reference example 1 5-methyl-2-phenyl-4-imidazole methanol benzamidine hydrochloride 100? at room temperature with a minimum amount of water (3
501!1I1).

Addition of freshly distilled 67r 2,3-butanedione results in a yellow solution. Adjusting the pH to 6-7 with 2N caustic soda produces a solid which, after standing at 0° C. for 2 hours, is collected, pressed dry and washed with 100 ml of acetone.

While stirring this material, add 855d of concentrated hydrochloric acid and 243d of
It dissolves when heated for 4 hours on a steam bath with 7 ml of water. = Leave overnight to cool to room temperature, and then cool to 0°C to obtain a solid, which is collected and air-dried. This solid is 35
Dissolved in 0 d of ethanol, passed through ▲, and cooled to form a gel. After 250 d of water, the gel was dissolved in water at ~60°C, adjusted to pH 5.5 with concentrated caustic soda, and then adjusted to pH 5.5 with solid KHCO3.
is set to 7-8. The mixture is cooled to 0° C. and the product is collected, washed with water, and air-dried. Recrystallization of the product from 1' methanol gives the final product with a melting point of 197-199°C. Instead of the above, this product can be prepared by the method of Im-Ch et al. (Bull
．． SOc. Chim. France, l97l, 105
(page 2).

Reference Example 2 2-Phenyl-4-imidazolemethanol This compound was prepared by the method of DziurOn and Schunax:k (Arch
．． P-Rm. , Vol. 306, p. 347 (1973) and Vol. 307, p. 46 (1974)).

Reference example 3 2'n-propyl-4-imidazole methanol 180
1,3-dihydroxyacetone dimer of y, butyramidine hydrochloride of 245f and liquid ammonia of 11 were added to 6
Warm in a bomb to 0°C for 5 hours.

The mixture is evaporated to dryness, the residue is stirred with 600 ml of 2-propanol, filtered, and the liquid is concentrated in vacuo. 600m
Add 1 part of 50% saturated sodium carbonate solution to each part of the mixture.
Extract three times with 50 ml of tetrahydrofuran.

The organic layers are combined and washed with 330 ml of saturated aqueous sodium carbonate solution. The organic layer is dried over anhydrous sodium sulfate and evaporated to dryness. The residue was recrystallized twice from acetone to a melting point of 9.
The title compound is obtained at a temperature of 5-101°C. Reference Example 4 2.5-Dimethyl-4-imidazolemethanol hydrochloride This compound is prepared by the method of Imbach et al. (see Reference Example 1).

Reference Example 5 2-Methyl-4-imidazole methanol When 189 V of acetamidine hydrochloride and 180 T of 1,3-dihydroxyacetone are combined with 11 of liquid ammonia as described in Reference Example 3, the melting point is 115 and ~117.5°C. The title compound is obtained.

Reference example 64,5-dimethyl-2-n-propyl-2-
Imidazoline-4,5-diol hydrochloride 112.7y of butyramidine hydrochloride is dissolved in 200d of water.

Add 107f7 of freshly distilled diacetyl and stir the mixture.

Adjust the pH to 6.5-7.0 with 2N NaOH and cool the solution.

The product is collected to give the title compound as a solid, mp 104-107°C. Reference Example 7 5-Methyl-2-n-propyl-4-imidazolemethanol The product of Reference Example 6 was mixed with 900 ml of water and 350 ml of water.
ml of concentrated hydrochloric acid, heated on a steam bath for 5 hours, and then cooled.

Concentrate the solution in vacuo, add a mixture of 100 ml of acetone and 100 ml of ethanol, and filter. The f solution is evaporated and the residue is dissolved in 50 ml of water and neutralized with a concentrated solution of K2CO3 until no bubbles are formed. Separate the upper layer and 5rn1
When mixed with methanol and left to stand, a precipitate will form. Collect the solid and dilute the liquid with acetone to form a second precipitate, which is also collected. The combined solids are recrystallized from acetone to give the title compound. Melting point 134°C to 136°C. Reference Example 85-Methyl-4-imidazolemethanol This compound was prepared by the method of Ewins [J. Chem. SOc. 9th
9, p. 2052 (1911)].

Reference Example 9 2-(0-propoxyphenyl)-4-imidazole methanol 130? of salicylamide is reacted with 52.4f of sodium methoxide and 164.9r of 1-iodopropane at reflux temperature.

The mixture is cooled and precipitated in 1500 ml of water and the solid is recrystallized from hot ethanol to yield o-propoxybenzamide. The above compound 109f7 was added to 500 ml of chloroform and refluxed for 3 hours with 49.4 ml of methyl fluorosulfonate.

After cooling, the mixture is concentrated to obtain an oil. When ether is added to this, crystals are formed and o-propoxybenzimic acid (
0-PrOpOxyberQimidicacid) methyl ester fluorosulfonate is obtained.

This last compound 180f and 55.0t of 1,3-dihydroxyacetone are combined into 11? When the compound is reacted in liquid ammonia as in Reference Example 3, the title compound having a melting point of 90° C. to 92° C. is obtained.

Reference example 10 2-benzyl-4-imidazole methanol 352f7
of benzyl cyanide, 750 ml of diethyl ether and 300 ml of dry ethanol are placed in 21 three-necked flasks.

The flask is equipped with a magnetic stirrer, a drying tube and a quick change gas inlet. Hydrogen chloride gas is bubbled through the mixture for 1 hour while stirring in an ice bath. After the mixture was placed in the cooling room overnight, the ether of 11 was added and the mixture was cooled. The precipitate is collected and washed with ether to obtain ethyliminophenyl acetate hydrochloride. When the above compound of 272r and 1,3-dihydroxyacetone of 126f7 are reacted in liquid ammonia of 11 as in Reference Example 3, the melting point is 1.
The title compound is obtained at 34°C to 135°C.

Reference example 11 2-methoxymethyl-4-imidazole methanol 30
7.2r ethyl 2-methoxyacetimidate (Et
hyl2-MethO Ccetimidate sulfate [Rule: J. Chem. SOc. 113, p. 9 (1918)] and 180 t of 1,3-dihydroxyacetone are reacted in 11 parts of liquid ammonia as in Reference Example 3 to obtain the title compound as an oil.

Heating this oily product in water with picric acid yields crystalline picrate (melting point 175-178°C). Reference example 12 2-t-butyl-4-imidazole methanol 326t
2,2-dimethylpropionamidine hydrochloride and 193
．． 5t of 1,3-dihydroxyacetone 2f! The title compound is obtained by reacting in liquid ammonia as in Reference Example 3.

Melting point: 212~221°C. Reference Example 13 2-t-Butyl-5-methyl-4-imidazolemethanol 200y of trimethylacetonitrile, 250TILI of methanol and 500ml of diethyl ether in a 2' three-loaf flask (with magnetic stirrer, drying tube and gas inlet tube) Put in.

After introducing hydrogen chloride gas into the solution for 2 hours with stirring, the mixture is transferred to a beaker, ether is added, the beaker is covered and stored in a cold room overnight. Add 500 mj of ether, filter the solid, and wash with ether to obtain white crystals of 2,2-dimethylpropionamidine hydrochloride.

The above substance 75f was prepared by the method of BrOwn and Evans (
J. Chem. SOc. 1962, 4039) to 2,2-dimethylpropionic acid amidine hydrochloride.

The latter compound is dissolved with warming in 50 ml of water and cooled to room temperature.

Reference example 6 by adding freshly distilled diacetyl 38.3f7
Continuing the reaction in the same manner as in step 7 yields the title compound with a melting point of 1
Obtained as white gun crystals at a temperature of 95.5°C to 196.5°C. Reference Example 14 α-phenylacetamidine hydrochloride of 2-benzyl-5-methyl-4-imidazolemethanol 109.6P [
Luckenbach,. Chem. Ber. l7,1
423 (1884)] in 50 μl of water and 55.4 μl of freshly distilled diacetyl are added to this solution.

Stir the mixture, collect the precipitate, grind it in small portions with 200 ml of acetone, and air dry to obtain 2-benzyl-4.
5-dimethyl-4,5-dihydroxyimidazolidine is obtained. This latter compound 106f is reacted with 170 ml of concentrated hydrochloric acid and 170 ml of water as described in Reference Example 7 to give the title compound.

Melting point: 134-138℃. Reference Example 15 2-Phenyl-4-imidazolecarboxaldehyde 17.4 tons of 2-phenyl-4-imidazole methanol and 13.4 WL1 of concentrated nitric acid are heated on a steam bath for 2 and a half hours.

Start the reaction by adding 3 drops of sulfuric nitric acid.

The pH is adjusted to 8 using concentrated Na2cO3 solution and the mixture is cooled to 0.degree. C. overnight. The solid was collected, washed with water, and recrystallized from a mixture of 70 ml of ethyl acetate and 20 ml of petroleum ether to give a yellow solid. Treatment of the mother liquor with petroleum ether yields a sticky substance, which is triturated with isopropanol to yield a second solid. These two solids are recrystallized in hot isoprobanol to obtain a yellow solid. Recrystallization of this solid from ethanol:water (1:1) gives yellow crystals of the title compound, melting point 169-171.5°C. Reference Example 16 2-n-propyl-4-imidazolecarboxaldehyde When a solution of 108.6f of 2-n-propyl-4-imidazole methanol dissolved in 107d of concentrated nitric acid is reacted in the same manner as in Reference Example 15, the melting point 103.5 cases to 10
The title compound is obtained at 5.5°C.

Reference Example 17 2-n-Butyl-4-imidazolecarboxaldehyde Following the general procedure of Reference Example 15, 2-n
-Butyl-4-imidazole methanol is converted to 2-n-butyl-4-imidazole carboxaldehyde.

Reference Example 18 5-Methyl-2-phenyl-4-imidazolecarboxaldehyde 102.1y of 5-methyl-2-phenyl-4-imidazole methanol is dissolved in 765d of concentrated nitric acid.

The solution is cooled in an ice bath and left for 16 hours.

The solution is heated on a steam bath for 30 minutes, diluted with 2.31 g of water and neutralized with 50% NaOH while cooling in an ice bath.
The solid matter was collected, dried, recrystallized from 200ml of ethanol, and then 11! Recrystallization from ethanol:water (1:2) gives the title compound, melting point 102-115°C.
In place of the above, the present compounds include Diels and Sdllei
ch method (Chem. Ber. 49, 1711 (19
16)).

Reference Example 19 5-Ethyl-2-phenyl-4-imidazole carboxaldehyde 5- used in the procedure of Reference Example 18
When the same procedure was repeated using an equimolar amount of 5-ethyl-2-phenyl-4-imidazole methanol in place of methyl-2-phenyl-4-imidazole methanol, the title compound was obtained in a similar good yield. It will be done.

Reference example 2,5-dimethyl-4- of 20205-dimethyl-4-imidazole carboxaldehyde 42.2r
Mix the imidazole methanol and 44.8 mi of concentrated nitric acid, and when the initial reaction has subsided, heat the solution on a steam bath for 1 hour.

After neutralizing the reaction mixture with concentrated aqueous sodium carbonate solution, it is concentrated in vacuo. After extracting the residue several times with 150 ml of hot ethanol, the combined organic solutions are concentrated in vacuo. The residual oil is subjected to silica gel chromatography to obtain a solid.
Recrystallization of this from isopropanol monoethyl acetate gives the title compound having a melting point of 164.5-166°C. Reference Example 215-Methyl-4-imidazolecarboxaldehyde This compound is prepared by the method of Hubball and Pyman (J. Chem. SOc, 1928, 21).

Reference Example 22 2-0-Propoxyphenyl-4-imidazolecarboxaldehyde 44f of 2-(0-propoxyphenyl)-4-imidazole methanol was mixed with 500TILI of chloroform and 100f of manganese dioxide in a 2' round bottom flask. insert.

The reaction mixture is refluxed with stirring for 5.5 hours. The reaction mixture is filtered hot. ≦U Manganese dioxide is triturated with 500 ml of hot chloroform and filtered.

The two F filtrates were combined and evaporated, and the residue was recrystallized using 200 ml of hot ethyl acetate and activated carbon to give an acid with a melting point of 104 to 1.
The title compound is obtained at 05°C. Reference example 23 2-methyl-4-imidazole carboxaldehyde 1
Divide 43.0t of concentrated nitric acid into 2 parts of 119.2f7.
-Methyl-4-imidazole Add to methanol.

After the first addition, the mixture is cooled and reacted in the same manner as described in Reference Example 15 to obtain the title compound. Melting point 170 to 176°C.
Alternatively, the present compounds can be prepared by the method of Streith et al. (Bull.
SOO. Chim. FranCe, 4l59 (1971
)) and (the method of Abush et al. (J.Org.C
hem. 4O3376 (1975)) VC.

Reference Example 24 2-Benzyl-4-imidazole carboxaldehyde 125?Same as Reference Example 22? of 2-benzyl-4-imidazole methanol and 500f7 of manganese dioxide.
When reacted in chloroform of 1, the melting point is 1302-13
The title compound is obtained at 6°C.

Reference example 252-(methoxymethyl)-4-imidazole carboxaldehyde Same as Reference example 15 145.9
2-methoxymethyl-4-imidazole methanol (r) and concentrated nitric acid (137d) are reacted.

After adjusting the pH to 7.0 with a concentrated aqueous sodium carbonate solution, the solution is concentrated in vacuo. After extracting the residue three times with hot ethanol,
The extracts are combined and concentrated to give a yellow gum. This is chromatographed on silica gel to combine the 7-lactones 7-15, then recrystallized from 120 ml of isopropanol and treated with charcoal to give the title compound.
Melting point 100~130°C. Reference example 26 2-benzyl-5-methyl- of 2-benzyl-5-methyl-4-imidazolecarboxaldehyde 8.79P
A mixture of 4-imidazole methanol and 55.7 ml of concentrated nitric acid is left overnight at room temperature.

The solution is heated on a steam bath for 45 minutes, cooled and then made alkaline with aqueous sodium carbonate solution. The mixture is heated on a steam bath and then cooled to collect the solids. Recrystallization twice from ethanol gives the title compound, melting point 171-173°C. Reference Example 27 2-benzyl-5-n-propyl-4-imidazolecarboxaldehyde 2-benzyl-5-methyl-4-imidazole in Reference Example 26 instead of 2-benzyl-5-n-propyl-4- If the same procedure is carried out using imidazole methanol, the present compound is obtained.

Reference example 5-methyl-2 of 285-methyl-2-n-propyl-4-imidazole carboxaldehyde 80y
-n-propyl-4-imidazole methanol at 67.
Oxidize with 3d concentrated nitric acid.

A second portion 101.4y of the above compound is oxidized with 77 ml of concentrated nitric acid. Combine the reaction mixture and stir.Reference Example 25
Treatment in the same manner gives the title compound.

Melting point 126-129°C. Reference Example 29 2-t-Butyl-4-imidazolecarboxaldehyde 7.7r of 2-t-butyl-4-imidazole methanol is added to 100a of chloroform and 100d of tetrahydrofuran and heated gently.

25r of manganese dioxide is added and the mixture is treated as described in Reference Example 22 to give the title compound as white crystals.

Melting point 194 and ~195°C. Reference Example 30 2-t-Butyl-5-methyl-4-imidazole carboxaldehyde 19.76r 2-t-butyl-5 as in Reference Example 25
-Methyl-4-imidazole methanol and 16.511
Reaction of L1 with concentrated nitric acid gives the title compound having a melting point of 1967-198°C.

Reference Example 31 2-isobutyl-5-isopropyl-4-imidazolecarboxaldehyde 2-t-butyl-5-methyl-4-imidazole in Reference Example 30 was replaced with an equimolar amount of 2-isobutyl-5-isopropyl- The same procedure was performed using 4-imidazole methanol.

The title compound is obtained with approximately equal good yields. Reference Example 32 Imidazole-4-carboxaldehyde (PymBn.J.Chem.SOc
．． 19l6, 186) in 200aQ hot ethanol.

Methyl dithiocarbazate of 24.4f [Audrieth et al.; J. Or-G. Chem. ↓Dan 733 (1954)] dissolved in 50 d of ethanol is added.

A precipitate immediately forms and the mixture is heated and stirred for about 10 minutes. Cool the mixture to 0°C. When the precipitate is collected, the melting point is 259 degrees ~
Yellow crystals at 261°C are obtained. Reference Example 33 35 t of 3-(2-phenyl-4-imidazolylmethylene)dithiocarbazic acid methyl ester of 2-phenyl-4-imidazolecarboxaldehyde was added to 250 ml of 2-phenyl-4-imidazolecarboxaldehyde,
Take in hot ethanol.

40! A solution of 22.8 r of methyl dithiocarbazate in nl of hot ethanol is added and treated according to the procedure of Reference Example 32 to give the title compound.

Melting point 166~170℃. Reference Example 34 3-[(5-Methyl-2-phenyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester As described in Reference Example 32, 60 tons of 5-methyl-2-phenyl-4-imidazole carboxylic acid Aldehyde and 36.8P
When reacting with methyl dithiocarbazate, the melting point was 180.
The title compound is obtained at ~185°C.

Reference Example 35 3-[(5-Ethyl-2-phenyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester 5-ethyl-2-phenyl-4-imidazole carboxyl following the general procedure of Reference Example 34 aldehy, do 3- [(5
-ethyl-2-phenyl-4-imidazolyl)methylene]dithiocarbazate methyl ester.

Reference example 36 3-(2-n-propyl-4-imidazolylmethylene)
Methyl dithiocarbazate When 60y of 2-n-propyl-4-imidazolecarboxaldehyde and 53.7r of methyl dithiocarbazate are reacted according to the method of Reference Example 32, the title compound having a melting point of 95-104°C is obtained. get.

Reference example 2 of 373-(2-methyl-4-imidazolyl-methylene)dithiocarbazate methyl ester 33t
-Methyl-4-imidazole carboxaldehyde and 4
0.3y of methyl dithiocarbazate is reacted as described in Reference Example 32 to give the title compound having a melting point of 274°C to 279°C.

Reference Example 383-(5-Methyl-4-imidazolylmethylene)dithiocarbazic acid methyl ester 16r 5-methyl-4-imidazolecarboxaldehyde and 19.5r methyl dithiocarbazate were reacted by the method of Reference Example 32. Melting point: 180℃ (decomposition), re-solidification
The title compound is obtained at 300-260°C.

Reference Example 39 3-[(2,5-dimethyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester By the method of Reference Example 32, 20t of 2,5-dimethyl-4-imidazolecarboxaldehyde and 20.8f7 of Reaction with methyl dithiocarbazate gives the title compound having a melting point of 279°C to 281°C.

Reference Example 403 {[2-(methoxymethyl)-4-imidazolyl]methylene}dithiocarbazic acid methyl ester 40f7 of 2-(methoxymethyl)-4-imidazolecarboxaldehyde and 38 by the method of Reference Example 32
．． Reaction of 4f7 with methyl dithiocarbazate gives the title compound, melting point 1500-154°C.

Reference Example 41 3-[(5-Methyl-2-n-propyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester 20y of 5-methyl-2-n-propyl-4-imidazolecarboxylate was prepared by the method of Reference Example 32. Kuzualdehyde and 17.
7t of methyl dithiocarbazate yields the compound of title Z4 having a melting point of 175°C to 179°C.

Reference Example 42 3-[(2-benzyl-5-n-propyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester 5-methyl-2-n-propyl-4-imidazole carboxy in the method of Reference Example 41 2 instead of aldehyde
-Benzyl-5-n-propyl-4-imidazole The same procedure using carboxaldehyde gives the title compound.

Reference example 433-[(2,5-dimethyl-4-imidazolyl)methylene]carbazic acid ethyl ester Reference example 3
When 6.2f 2,5-dimethyl-4-imidazole carboxaldehyde and 6.24y ethyl carbazate are reacted by method 2, the melting point is 207.5 to 210°C.
The title compound (resolidification point 248-252°C) is obtained.

Reference example 44 3-(2-n-propyl-4-imidazolylmethylene)
7 by the method of Carbazic Acid Ethyl Ester Reference Example 32
．． 8f7 2-n-propyl-4-imidazole carboxaldehyde and 6.24? Reaction of ethyl carbazate gives the title compound having a melting point of 1800-182°C.

Reference Example 453-(2-phenyl-4-imidazolylmethylene)carbazate ethyl ester When 8.16r of 2-phenyl-4-imidazolecarboxaldehyde and 5.52f of ethyl carbazate are reacted by the method of Reference Example 32, The title compound is obtained, melting point 196f-200°C.

Reference example 463-[(5-methyl-2-phenyl-4-
(imidazolyl)methylene]carbazic acid ethyl ester 10.25r of 5-methyl-2-phenyl-4-imidazolecarboxaldehyde and 5.72f7 of ethyl carbazate are mixed in 30ml of ethanol containing 1 drop of acetic acid. Boil for 30 minutes.

The mixture is cooled to 0° C. and compressed under a stream of air over a steam bath. 50 d of carbon tetrachloride are added and the mixture is cooled to 0° C. overnight.

Collecting the solid gives the title compound, mp 209-211°C. Reference example 47 3-[(2-0-propoxyphenyl-4-imidazolyl)methylene]carbazic acid ethyl ester Reference example 32
4.3t of 2-0-proboxyphenyl-4-imidazolecarboxaldehyde and 1.98f7
When ethyl carbazate is reacted, the melting point is 129f~1
The title compound is obtained at 32°C.

Reference example 48 3-[(2-benzyl-4-imidazolyl)methylene]
Carbazic acid ethyl ester in 200ml of ethanol 37.2? To the 2-benzyl-4-imidazole carboxaldehyde is added 20.8 f7 of ethyl carbazate and a few drops of concentrated acetic acid.

The mixture is reacted according to the method of Reference Example 32 to obtain the title compound having a melting point of 184 to 185°C. Reference example 493-(2
-t-butyl-4-imidazolylmethylene)carbazic acid ethyl ester 7.6t of 2
Reaction of -t-butyl-4-imidazolecarboxaldehyde and 5.2r ethyl carbazate in 100 ml of ethanol gives the title compound, melting point 1941-197°C.

Reference Example 50 3-(2-n-butyl-4-imidazolylmethylene)carbazic acid ethyl ester In the method of Reference Example 49,
If an equimolar amount of 2-n-butyl-4-imidazolecarboxaldehyde is used in place of 2-t-butyl-4-imidazolecarboxaldehyde, the title compound is obtained with equally good yields.

Reference Example 51 3-(2-Methyl-4-imidazolylmethylene)carbazic acid ethyl ester 16. A solution of 68 f7 of ethyl carbazate dissolved in 50 ml of hot ethanol was dissolved in 16.
50? 2-Methyl-4-imidazolecarboxaldehyde is dissolved in 100a of hot ethanol and added to a solution of 2 drops of acetic acid.

When the reaction is carried out as described in Reference Example 32, the melting point is 210.
．． Example 5 The title compound is obtained at 211.5°C. Reference example 5
2 Aυ 3-(5-methyl-4-imidazolylmethylene)carbazic acid ethyl ester 7.0 by the method of Reference Example 32
Reaction of t 5-methyl-4-imidazolecarboxaldehyde with 7.3r ethyl carbazate gives the title compound, melting point 195°-203°C.

Reference Example 533-[2-(methoxymethyl)-4-imidazolyl]methylenecarbazic acid ethyl ester By the method of Reference Example 32, 19.60f7 of 2-(methoxymethyl)-4-imidazolecarboxaldehyde and 16.
When 02y is reacted with ethyl carbazate, the melting point is 186.
The title compound is obtained at y~190<0>C.

Reference Example 54 3-[(2-benzyl-5-methyl-4-imidazolyl)methylene]carbazic acid ethyl ester 4.08t of 2-benzyl-5-methyl-4 was prepared by the method of Reference Example 32.
- When imidazole carboxaldehyde is reacted with 2,29t ethyl carbazate, the melting point is 190t~191
．． The title compound is obtained at 5°C.

Reference example 55 3-[(2-t-butyl-5-methyl-4-imidazolyl)methylene]carbazic acid ethyl ester Reference example 32
6.17t of 2-t-butyl-5-methyl-4-imidazolecarboxaldehyde and 4.20t of
When reacting with ethyl carbazate, the melting point is 226t~2
The title compound is obtained at 28.5°C.

Reference Example 56 3-[(2-isobutyl-5-iso-propyl-4-imidazolyl)methylene]carbazic acid ethyl ester 2-isobutyl-5-isopropyl-4-imidazolecarboxylate according to the general method of Reference Example 55 Cusaldehyde is converted to the title compound with equally good yields.

Reference Example 57 3-[(5-Methyl-2-n-propyl-4-imidazolyl)methylene]carbazic acid ethyl ester Zt 5-Methyl-2-n- of 12r by the method of Reference Example 32
Propyl-4-imidazole carboxaldehyde and 9
．． When ethyl carbazate of 06r is reacted, the melting point is 18
The title compound is obtained from 4r to 188°C.

Example 1 Imidazo[1.5-d]-As-triazine-4 (3H
)-thione 1.21 in diphenyl ether 164.5
The suspension of 3-(4-imidazolylmethylene)dithiocarbazic acid methyl ester of r is stirred and heated to 175°C until the generation of methyl mercaptan ends (20 minutes).

The precipitate obtained after cooling to room temperature is collected and washed successively with petroleum ether and then with acetone. If the precipitate is slurried in boiling methanol at 1.21 °C and heated at F.
The title compound is obtained at °C. Example 2 8-Methyl-imidazo[1.5-d]-A8-triazine-4(3H)-thione 14.39r of 3-(5-methyl-4-imidazolylmethylene)dithio in 100d of diphenyl ether When a suspension of carbazic acid methyl ester is reacted as described in Example 1, a melting point of 262
The title compound is obtained as yellow crystals at ~268°C.

Example 36-phenylimidazo[1.5-d]-A
s-triazine-4(3H)-thione 7.05t of 3-(2-phenyl-4) in 100d of diphenyl ether
A suspension of dithiocarbazic acid methyl ester (imidazolylmethylene) is reacted as described in Example 1 to give the title compound having a melting point of 210°C.

Example 4 6-n-propylimidazo[1.5-d]-As-triazine-4(3H)-thione 102.2r of 3-(2-n-propyl-4) in 500d of diphenyl ether
-Imidazolylmethylene) dithiocarbazic acid methyl ester is reacted in the same manner as in Example 1, and the melting point is 201.5.
to obtain the title compound as a white solid at ~203.5°C.

Example 5 8-methyl-6-phenylimidazo[1.5-d]-
As-triazine-4(3H)-thione 73.4y 3
-[(5-methyl-2-phenyl-4-imidazolyl)
methylene]dithiocarbazic acid methyl ester and 5
00 ml of diphenyl ether are reacted as described in Example 1 to give the title compound as purple crystals with a melting point of 237.5°C to 239°C.

Example 6 3-[(
2,5-dimethyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester and 125! A mixture of nl diphenyl ethers is reacted as described in Example 1 to give the title compound, melting point 287.5-290°C.

Example 7 6-benzyl-8-methyl-imidazo[1.
5-d]-As-triazine-4(3H)-thione2.
04? 2-benzyl-5-methyl-4-imidazole carboxaldehyde is dissolved in 20 RI of ethanol containing 2 drops of acetic acid.

1.34? of methyl dithiocarbazate is added and the mixture is boiled for 30 minutes and then cooled to 0° C. overnight.

Evaporation of the mixture yields 3-[(2-benzyl-5-methylimidazolyl)methylene]dithiocarbazic acid methyl ester as an oil. Dissolve 3.40f7 of the above product in 30a diphenyl ether 1947-20
Heat to 7°C for 9 minutes.

The mixture is cooled to room temperature and diluted with hexane. The solid is recrystallized from 150 ml of methanol and treated with charcoal to give the title compound, melting point 207.degree.-209.5.degree. Example 8 8-Methyl-6-n-propyl imidazo[1.5-d
]-As-triazine-4-(3H) monothione 32.1
When the 3-[(5-methyl-2-n-propyl-4-imidazolyl)methylene]dithiocarbazate methyl ester of 2r and the diphenyl ether of 200d are reacted as described in Example 1, the melting point is 183 m.p. The title compound is obtained at 186°C.

Example 9 6-Methyl-imidazo[1.5-d]-As triazine-4(3H)-thione 53.9? 3-(2-methyl-
4-Imidazolylmethylene)dithiocarbazic acid methyl ester and diphenyl ether of 200 WLI are reacted as described in Example 1 to give a melting point of 280.5 m-28
The title compound is obtained at 4°C.

Example 10 6-methoxymethyl-imidazo[1.5-d]-As-
Triazine-4(3H)-thione 62.4f 3-[2
-(Methoxymethyl)-4-imidazolyl]methylene dithiocarbazate methyl ester and 250 ml of diphenyl ether are reacted as described in Example 1 to give the title compound with a melting point of 219.5°C to 223°C.

Example 116-0-propoxyphenylimidazo [
1,5-d]-As-triazin-4(3H)-one 1
0.5f of 3-[(2-0-propoxyphenyl-4-
Add imidazolyl)methylene]carbazic acid ethyl ester to 100ml of diphenyl ether and add 255 to ~
Heat with stirring on an oil bath at 265° C. until foaming stops.

The mixture is cooled to room temperature and petroleum ether is added to form a solid. The solid is collected and recrystallized from methanol with the aid of charcoal to give the title compound as a light yellow solid, mp 197-200°C. Example 12 6-benzylimidazo[1,5-d]-Astriazin-4(3H)-one 7.0f in diphenyl ether of 501/31[(2-benzyl-4-imidazolyl)
Methylene]carbazic acid ethyl ester is reacted as described in Example 11 to give the title compound as white crystals with a melting point of 215-217°C.

Example 13 6-Phenylimidazo[1,5-d]-As-triazin-4(3H)-one 7.76f of 3-(2-phenyl-4-imidazolylmethylene)carbazic acid ethyl ester In addition to enyl ether Example 1
When reacted as described in 1, the melting point is 245 to 248.
The title compound is obtained at °C.

Example 14 8-Methyl-6-phenylimidazo[1.5-d]-
As-triazin-4(3H)-one 8.33y 3-
[(5-Methyl-2-phenyl 4-imidazolyl)methylene]carbazic acid ethyl ester is added to 60TIL1 of diphenyl ether and heated on an oil bath to 2150-230°C for 20 minutes.

The reaction mixture was diluted to 400 TILI with petroleum ether and the precipitate was collected and recrystallized from 350 TILI of benzene to give the title compound having a melting point of 1823-184.5°C. Example 15 6-n-propylimidazo[1.5-d]-As-triazin-4(3H)-one 8.75y of 3-(2-n
-Propyl-4-imidazolylmethylene)carbazic acid ethyl ester 50! When added to diphenyl ether of FIl and reacted as described in Example 11, the melting point was 15.
The title compound is obtained at 9°C to 162,5°C.

Example 16 6,8-dimethyl-imidazo[1,5-d]-As-triazin-4(3H)-one 7.37y of 3-[(2
・When a mixture of 5-dimethyl-4-imidazolyl)methylene]carbazic acid ethyl ester and 50 ml of diphenyl ether is reacted in the same manner as in Example 11, the melting point is 263.
The title compound is obtained at ~263.5°C.

Example 17 3-(2-t-
Butyl-4-imidazolylmethylene)carbazic acid ethyl ester is added to 40 ml of diphenyl ether and reacted as described in Example 11, with a melting point of 186 m.p.
The title compound is obtained at 8°C.

Example 18 6-Methyl-imidazo[1,5-d]-Astriazin-4(3H)-one 2.7.2V of 3-(2-methyl-
Example 1 Adding 4-imidazolylmethylene) carbazic acid ethyl ester to 200 WLI of diphenyl ether
Reaction in the same manner as in 1 gives the title compound having a melting point of 303 to 305.5°C.

Example 19 8-Methyl-imidazo[1,5-d]-As triazin-4(3H)-one 3-(5-methyl-4-imidazolylmethylene)carbazate ethyl ester of 10.26f7 and diphenyl of 1007n1 Example 1 of ether
Reaction as in 1 gives the title compound having a melting point of 276-282°C.

Example 20 6-benzyl-8-methyl-imidazo[1.5-d]-
As-triazin-4(3H)-one 4.89y 3-
Reaction of [(2-benzyl-5-methyl-4-imidazolyl)methylene]carbazic acid ethyl ester and 50 ml of diphenyl ether as in Example 11 gives the title compound with a melting point of 244 °C to 247 °C.

Example 21 6-t-butyl-8-methyl-imidazo [1.5-d]
-As-triazin-4(3H)-one 5.111-3
-[(2-t-butyl-5-methyl-4-imidazolyl)methylene]carbazic acid ethyl ester and 507n1
The diphenyl ether of is reacted as in Example 11 to give the title compound, melting point 198-200°C.

Example 22 8-Methyl-6-n-propyl imidazo[1.5-d
]-As-triazin-4(3H)-one 14.50V
3-[(5-methyl-2-n-propyl-4-imidazolyl)methylene]carbazic acid ethyl ester and 10
Diphenyl ether of 0W11 is reacted in the same manner as in Example 11 to obtain the title compound having a melting point of 129.5°C to 131.5°C.

Example 236-Methoxymethyl-imidazo[1,5-
d]-As-triazin-4(3H)-one 25.9f
7 of 3-[2-(methoxymethyl)-4-imidazolyl]methylenecarbazate ethyl ester and 1257 fL
The diphenyl ether of Example 1 is reacted as in Example 11 to give the title compound having a melting point of 2000-205°C.

Example 24 8-bromo-6-phenylimidazo[1.5-d]-
As-triazin-4(3H)-one 3.0y of 6-phenylimidazo[1.5-d]As-triazine-4
(3H)-one is stirred with 100 ml of chloroform.

The mixture was heated slightly and 17n in 10ml of chloroform was added.
The bromine solution of 1 is added dropwise into the reaction mixture. The mixture is heated under reflux for 1 hour, then cooled to room temperature and filtered. Na2cO3 aqueous solution and chloroform were added to the obtained solid, and the mixture was shaken in a separatory funnel. The residual solid and organic phase are combined and evaporated on a steam bath. Add methanol and 2-propanol and treat the mixture twice with charcoal. Melting point: 192 when cooled
The title compound is obtained at 194°C. Example 258-Chloro-6-phenylimidazo[1.5-d]-As-triazin-4(3H)-one 5.0? 6-phenylimidazo[1,5-d]As-triazine-4(3H)-
100Ir11 of chloroform and bubbled chlorine gas into the mixture on a steam bath.

Add 25W11 methanol and pass chlorine gas through for another 10 to 15 minutes.

Cool the mixture to room temperature, transfer to a separatory funnel, and add Na2cO3.
Wash with aqueous solution, NaHSO3 aqueous solution and finally water. The mixture is evaporated on a steam bath to 75 mi and filtered after cooling. ▲If the liquid is evaporated overnight, a solid will remain. This solid is 3
Dissolve in 0ml of hot chloroform and filter. ▲ Treating the liquid with charcoal and adding 2-propanol gives the title compound with a melting point of 201 and ~203°C. Example 26 8-methyl-6-phenylimidazo[1.5d]-A
8-Methyl-6-phenylimidazo[1.5-d]-As- of s-triazine-4(3H)-thione 4.5V
57 phosphorus pentasulfide is added to a solution of triazin-4(3H)one in 100 TfLj of pyridine.

The reaction mixture is heated to 100° C. for 8 hours and then poured into dilute hydrochloric acid. The precipitated title compound is separated ▲, washed with water, and then dried. Example 27 8-chloro-6-phenylimidazo[1.51d]-
As-triazin-4(3H)-one When 5-chloro-2-phenyl-4-imidazole carboxaldehyde and ethyl carbazate are used in the method of Reference Example 46, 3-[(5-chloro-2-phenyl-4 -imidazolyl)methylene]carbazic acid ethyl ester is obtained,
When this is heated in diphenyl ether in the same manner as in Example 11, it is converted to the title compound.

Reference Example 58 5-Methyl-2-m-tolyl-4-imidazole methanol cis and trans-4,5-dimethyl-21m-
Tolyl-2-imidazoline-4,5-diol hydrochloride (
9.07, 0.035 mol) and 3N hydrochloric acid (135W11
) The mixture was stirred on a steam bath for 2.5 hours. *After stirring and heating, the mixture was further stirred at 0 to 5°C for 0.75 hours.

The reaction mixture was filtered to give 7,47 (0.031 mol) of a white solid. Treatment of this solid with base provides the title compound. Melting point 1900-192°C (decomposed). Analysis: C
Calculated value of l2Hl4N2O; C7l. 26;H6.98
; Nl3.85; Actual value: C7O, 94:H7. O7;
Nl3.92.

Other imidazole methanol compounds prepared by the above method are shown in Table 3 below.

Reference Example 59 Preparation of 2-monosubstituted 5-methyl-4-imidazolecarboxaldehyde Method A 5-Methyl-2-m-tolyl-4-imidazolecarboxaldehyde 5-methyl-2-m-tolyl-4- Imidazole methanol (13.0t10.064mol),
Activated manganese dioxide (65y) and methylene chloride (
The mixture of 200w11) is stirred at room temperature for 20 hours.

Next, the reaction mixture was filtered and the solvent was removed in vacuo, resulting in 9.1r
(0.045 mol) of a pink solid is obtained. Method B 5-Methyl-2-(p-nitrophenyl)-4imidazole carboxaldehyde-imidazole methanol (2.9f
、． 0.012 mol) and 70% nitric acid (20 WL0 to 50
Stir for 3 hours at ℃, then dilute with water and neutralize with base.

When the precipitated yellow solid is collected by f, 2.4f (0.01
1 mol) of the title compound is obtained. Decomposes above 270°C.

Analysis: Calculated for CllH, N3O3: C, 57.
1a; Hl3.92; Nll8. l7; Actual value: Cl5
6.69; Hl3.96; Nll8. O8OC method 2-
Preparation of alkyl(cycloalkyl)-5-methylimidazole-4-canoleboxanoledehyde 2-alkyl(cycloalkyl)-5-methyl-4-imidazole methanol (0.1 mol), activated dioxide Manganese (0
．． 5 mol) and chloroform (500r111) at 2
Stir and reflux for an hour and then stir at room temperature overnight (about 15-16 hours).

After filtering the mixture through a bed of filter aid, the solution is evaporated to dryness and the residue is recrystallized from a suitable solvent. Many 2-substituted 5-methyl-4-imidazole carboxaldehydes are produced by any of the above production methods.

The compounds, their preparation methods, melting points and analytical results are shown in Table 4 below. Reference Example 60 α-Methyl-2-phenyl-4-imidazole Methanol 2-phenyl-4-imidazole carboxaldehyde (3.0 V, .0.017
mol) solution of methylmagnesium bromide (15.3
m1, a 2.5 molar solution in ether) is added dropwise.

Meanwhile, the reaction mixture is cooled and kept at 25°C. 2 of the mixture
After stirring for a while, a large amount of water is added dropwise to cause decomposition. The mixture was extracted with ether (3 x 75ml) and the ether extract was partially evaporated to give a white precipitate. Crystalline alcohol, melting point 197-198°C o Analysis: Calculated as CllHl2N2O: C, 70.19; H, 6.43; N, 14.
88; Actual value: Cl7O. lO; Hl6.68; Nll
4.9OOα-5-Dimethyl-2-phenyl-4-imidazolemethanol The title compound ( 3
8.4795.5%) is obtained as a white crystalline solid.

Melting point: 189-190°C. Reference Example 62 Preparation of methyl 2-phenyl-4-imidazolyl ketone To a solution of methyl-2-phenyl-4-imidazole methanol (3.0 t, .0.016 mol) in acetone (25 ml), JOnes reagent [5 ml; Chromium oxide (1
0.3y) with sulfuric acid (8.7!!11) and water (30ml)
[solution added into the mixture] at a temperature of 00-5°C over a period of 1 hour.

The temperature was raised to 20°C for 30 minutes, then water (-150°C
Add m1). Ru. The solids are treated with 2N hydrochloric acid (15 mO), stirred for 5 minutes and then neutralized with 10% caustic soda.
The aqueous mixture was extracted with methylene chloride (75 ml x 3) and the methylene chloride was removed from the extract, the melting point was 158 ~ 15
The title ketone is obtained as a white crystalline solid (1.737) at 8.5°C. Analysis: Calculated values as C,, Hl2N2O:
C, 70.95; Hl5.4l; Nll5. O4; Actual value: Cl7O. 34; Hl5.52; Nll5. O8.

Reference example 63 methyl-5-methyl-2-phenyl-4-
Production of imidazolyl ketone By the method of Reference Example 62, α・
The title compound is obtained from 5-dimethyl-2phenyl-4-imidazole methanol (12.0y.0.059 mol).

The product is a pale yellow crystalline solid with a melting point of 188°C to 190°C (
6.887, 58.3%). Analysis: C,2Hl2
Calculated for N2O: C, 71.98; Hl6. O4
;Nll3.99;Actual value:Cl7l. 3O; Hl6.
29; Nll3,4OO Reference example 642-phenyl-5
- Preparation of imidazole carboxaldehyde dimethyl acetal 2-phenyl-5 imidazole carboxaldehyde (6.107,0 ml) in methanol (200 ml)
．． After cooling the solution of 0.35 mol) in an ice bath, it is saturated with hydrogen chloride.

The reaction mixture was stirred overnight (approximately 15-16 hours) and then cooled to 6
Slowly pour into N caustic soda (200rf11). After neutralizing the solution with concentrated hydrochloric acid, collect the precipitate by filtration (7.56V.0
．． 035 mol). Recrystallization from chloroform gives white needles. Melting point 158~160℃ o Analysis: Cl2H
,4N2O2: C, 66.03; Hl6
．． 48; Nll2.83; Actual value: Cl65.38; H
, 7.01; N, 12.630 Reference example 65 Production of 4-iodo-2-phenyl-5-imidazole carboxaldehyde dimethyl acetal and 4-iodo-2-phenyl-5-imidazole carboxaldehyde Methanol (200 m0, water (20111) and 2-phenyl-5-imidazole carboxaldehyde dimethyl acetal (7.
Iodine (10.25 y
10.0404 mol) solution is added.

The reaction mixture is stirred for 5 hours and then concentrated in vacuo to a volume of about 75 ml. 4- precipitated by adding water (200w11)
Iodo-2-phenyl-5-imidazole carboxaldehyde dimethyl acetal (2.82t10.008
2 moles) are collected. Melting point 144-148.5°C (decomposed). The aqueous solution was acidified with concentrated hydrochloric acid to precipitate 4-iodo-2-phenyl-5-imidazocarboxaldehyde (
5.51f10.018 moles) are collected.

Melting point 208-210°C (decomposed). Recrystallization of 4-iodo-2-phenyl-5-imidazolecarboxaldehyde dimethyl acetal from methylcyclohexane gives white crystals with a melting point of 152-153.5°C.

Analysis: Calculated value as Cl2Hl3N2Ol: Cl4l
．． 88; Hl3.82; Nl8. l4; Actual value: C, 4
l. 82; Hl4. l9; Nl8.34O4-iodo-
When 2-phenyl-5-imidazolecarboxaldehyde is recrystallized from ethyl acetate, the melting point is 211.5-212.
．． Obtain white crystals at 5°C.

Analysis: Calculated as ClOH7N2Ol: Cl4O.
29; Hl2.37; Nl9.39; Actual value: Cl4O
．． 19; Hl 2.37; Nl 9.34. Reference example 663
-Production method of [(2-monosubstituted-5-methyl-4-imidazolyl)methylene]carbazic acid methyl ester A. 3-[
(5-Methyl-2-m-tolyl-4imidazolyl)methylene]-carbazic acid, methyl ester 5-methyl-2
-m-Tolyl-4-imidazolecarboxaldehyde (6.97, 0.034 mol), methyl carbazate (
3.17, 0.034 mol), methylene chloride (70W1
A mixture of 0 and acetic acid (1 drop) is refluxed for 1 hour.

When the precipitated white solid was collected by filtration, the yield was 7.1V (0.
026 mol), melting point 162 DEG -164 DEG C. Several diaryl analogs of the above compounds are prepared by the above method.

These compounds, their melting points and analytical values are shown in Table 5 below. B. 3-[(2-alkyl or cycloalkyl 5-
methyl-4-imidazolyl)methylene]rubadic acid,
Production of methyl ester 2-alkyl (cycloalkyl)
A mixture of -5-methylimidazole-4-carboxaldehyde (0.1 mol), methyl carbazate (0.1 mol), toluene (60 ml) and acetic acid (0.5 ml) is refluxed for 2 hours.

The reaction mixture is cooled and the solid is filtered and recrystallized from a suitable solvent. The 2-alkyl and cycloalkyl compounds prepared by the above procedure are shown in Table 5 below. Reference example
673-[1-(5-iodo-2-phenyl-4-imidazolyl)ethylidene]carbazic acid, preparation of methyl ester methanol (50d), toluene (250d),
Acetic acid (1 ml) and methyl carbazate (1.73
4-iodo-2-phenyl-5-imidazole carboxaldehyde (5.t, 0.019 mol) in a mixture of
21r, 0.017 mol) is refluxed for 24.5 hours.

The solution was then heated for another hour and the solvent (100!FLl
) is removed by distillation. Collect remaining solvent in vacuo. The solids were extracted with methylene chloride (3001 Ll) and the extract was washed with water (200 dX three times). At this point, the product crystallizes and is overcollected with f (2.16?, 0.0056 mol). When the F solution is evaporated, more products (3.44f,0
．． 0093 mol) is obtained. When recrystallized from methanol and methylene chloride, the melting point is 145-147°C (decomposition).
Obtain white crystals. Reference example 68 3-[5-methyl-2-phenyl-4-imidazolyl)
Production of ethylidene]carbazic acid, methyl ester 5-
Methyl-2-phenyl-4-imidazolyl ketone (4.
5f, 0.023 mol) to methyl carbazate (2.4
f7, 0.023 mol) together with toluene (1121LI
) for 5 hours.

Toluene was removed and the solid was washed with water (50ml x 3 times) and then recrystallized from methanol to give a product (title compound) (1.28r, 20.9%) with a melting point of 199X-201°C. Analysis: Calculated value as Cl4H,6N4O2: C,6
l. 75; H, 5.92; N, 2O. 57; Actual value: C
, 6O. O5; H, 6.25; Nll9.96. Reference example 693-[1-(2-phenyl-4-imidazolyl)
Preparation of ethylidene]carbazic acid, methyl ester According to the method of Reference Example 68, the title compound is obtained from 2-phenyl-4-imidazolyl ketone and methyl carbazate in a yield of 91%.

Melting point: 226.5-227°C. Analysis: Cl3H,4N,O
, calculated value as: C, 60.46; H, 5.46; N
, 2l. 69; Actual value: Cl6O. 59; H, 5.6O
;N, 2l. 89.

Example 28A Preparation of 8-methyl-6-m-tolyl-imidazo[1,5-d]-As-triazin-4(3H)-one 3-[(5-methyl-2-m-tolyl-4-imidazolyl )-methylene]carbazic acid methyl ester (
5,17,0.019 mol) and o-dichlorobenzene (
A mixture of 757 fL1) was gradually heated (45 minutes) to reflux temperature, refluxed for 1.5 hours, and then left at room temperature overnight (approximately 15-16
time) Stir.

Filter the reaction mixture to obtain 3.9f (0.016 mol) of the title compound. Recrystallization from o-dichlorobenzene gives a partially solvated product. Example 28B 8-Methyl-6-(p-nitrophenyl)-imidazo [
1,5-d]-As-triazin4(3H)-one, 1
Preparation of hydrate 3-{[2-(p-nitrophenyl)-5-methyl-4
-Imidazolyl]methylene}carbazic acid methyl ester (2.5y, 0.0082 mol) is immersed in diphenyl ether (25m0) at 240°C for 20 minutes and then stirred in an ice bath for 1 hour.

When the reaction mixture was diluted with ether and filtered, the reaction mixture was 2.27 (
0.008 mol) of the title compound are obtained. When this product is extracted with acetone sox, it has a melting point of 295~2.
A yellow solid at 97° C. is obtained. Example 28C Preparation of 6-alkyl(cycloalkyl)-8-methylimidazo[1,5-d]-As-triazine 4(3H)-one The title compound is produced in the same manner as in Method A above, except that 2 −
The difference is that the mixture of alkyl(cycloalkyl)-5-methylimidazole-4-carboxaldehyde methylcarbazone and o-dichlorobenzene is heated until a boiling point of 180°C is obtained.

The solvent is evaporated off and the residue is recrystallized from a suitable solvent.
Method A. Compounds produced in the same manner as B and C, their melting points and analysis results are shown in Table 6 below.

Example 29 6-phenyl-8-iodoimidazo[1.51d]-
Preparation of As-triazin-4(3H)-one 3-[1-
(5-Iodo-2-phenyl-4-imidazolyl)alkylidene]carbazic acid methyl ester (1.01y,
0.0027 mol) to o-dichlorobenzene (150 mol)
1) and methanol (15a), heat the solution to the boiling point, and then boil for 20 minutes to evaporate a portion of the solvent.

The reaction mixture was chromatographed on a silica gel column and eluted with a hexane-ethyl acetate (2:1) mixture to give the title compound (0.63f70.0019 mol). Recrystallization from ethyl acetate-hexane gives the product as yellow needles with a melting point of 170°C to 189°C. Example 30 6-(p-aminophenyl)-8-methyl-imidazo [
Preparation of 1,5-d]-As-triazin-4(3H)-one 8-Methyl-6-(p-
Nitrophenyl)-imidazo[1,51d]-AB-triazin-4(3H)-one monohydrate (1.3r,0.
0048 mol) is catalytically reduced with hydrogen.

Subsequently, the solvent was removed in vacuo to obtain the title compound (1.0t,
Recrystallization from dimethylformamide-water gives a mustard yellow solid with a melting point of 252°C to 254°C (decomposed). Example 318-bromo-6-(
m-aminophenyl)-imidazo[1.5-d]-As
-Production of triazin-4(3H)-one 8-Promo 6
-(m-nitrophenyl)imidazo[1.5-d]-A
s-triazin-4(3H)-one (2.0t, 0.0
0595 mol) and 11[′ − 1
ノ1h--8'R^ 8. List J-~4 Under a nitrogen atmosphere of r〒, add dimethylformamide (45rn1).

While vigorously shaking the flask containing the above mixture, hydrogen was introduced and absorbed (399 ml, 0.01785 mol). Next, separate the catalyst ▲ and wash with dimethylformamide. Evaporation of the liquid f in vacuo and recrystallization of the product from dimethyl ether gives the title compound, melting point 205° C. (decomposed). Example 328-Bromo-6-(m-dimethylaminophenyl)-imidazo[1.5-d]-As-triazine-4(
Preparation of 8-bromo-6-(m-aminoJ)-one
G-nyl) imidazo[1,5-d]-As-triazine-
4(3H)-one, formaldehyde aqueous solution (5mil
While stirring a solution of sodium cyanoborohydride (37%) in acetonitrile (11077!O)
．． 2, 0.019 mol) is added.

After stirring the reaction mixture for 15 minutes, acetic acid was added and the P
Adjust H to 7. The reaction mixture is stirred for 45 minutes, during which time the pH is maintained at 7 by adding acetic acid if necessary. The solvent was then evaporated in vacuo and the residual oil was dissolved in 2N caustic potash solution (150ml).
Add to crystallize. When the product is washed with water and recrystallized from acetone/water, its melting point is 206°C (decomposed). Example 33 6-(m-nitrophenyl)imidazo[1.51d]-
Preparation of A8-triazin-4(3H)-one A mixture of 90% fumed nitric acid (0.4 ml, δ=1.5, 0.0086 mol) and sulfuric acid (10 ml) was diluted with 6-phenyl at 5°C. Imidazo[1,5-d]-As-triazine-4(3H)
-one (2.12t.0.01mol) was added to sulfuric acid (50ml
) into the solution gradually.

The mixture is stirred at room temperature overnight (approximately 15-16 hours) and then poured onto ice. The mixture is made slightly alkaline, stirred with ethyl acetate and filtered. The separated solid is recrystallized from an aqueous dimethylformamide solution to obtain a pale yellow fluffy solid (32%) of 0.83f7. Melting point 294℃～
296°C (violent decomposition). analysis. Calculated value as CllH7N5O3: C, 51.36; H, 2.74; N, 2
7.23; Actual value: C, 5l. 28; Hl2.85; N
, 27. l7.

Example 348-bromo-6-(m-nitrophenyl)
imidazo[1,5-d]-As-triazine-4 (3H
)-one, preparation of compound with dimethylformamide 90
A mixture of 8-bromo-6-phenyl imidazo[1.5-d]- As-triazin-4(3H)-one (5.82 t, .0.02 mol) is slowly added to the solution in sulfuric acid.

The reaction mixture was stirred for 1 hour, poured onto ice, and the precipitate was dried separately to give a dark brown solid (6.58y, 98%). Melting point 244°C to 246°C (decomposition). Recrystallization from aqueous dimethylformamide gives the title compound as a pale yellow solid. Melting point 246°C to 248°C (decomposed). analysis.
Calculated value as CllH6BrN5O3.C3H7NO: C, 4l. O9; H, 3.2O; N, 2O. 54;B
r, l9.53; Actual value: C, 4O. 99; H, 3. l
5;N, 2O. 34; Br, 2O. 5O. Example 35
Preparation of 8-promoimidazo[1,5-d]-As-triazine-4(3H)-one A solution of bromine (8.0y, 0.05 mol) in acetic acid (10ml) was dissolved in imidazo[1,5-
d]-As-triazin-4(3H)-one (6.8f
7, 0.05 mol) and acetic acid (500 ml).

The reaction mixture was stirred for 1 hour, poured into water and extracted with chloroform. The aqueous layer is separated, made slightly alkaline, and extracted with ether. When chloroform and ether are removed by evaporation, 5
．． Obtain 0f solid (46.3%). Recrystallization of this solid gives the title compound as a cream colored solid with a melting point of 244°C to 245°C (decomposed). analysis. C, H3BrN
Calculated value as 4O: C, 27.8O:H, l. 4O;
N, 25.94; Br, 37. OO; Actual value: Cl28
．． 99; H, l. 36; N, 26.46; Br, 35.
9l. Example 36 6,8-dipromoimidazo[1,5-d]-As-triazine-4(3H)-oneimidazo[1,5-d]-
As-triazin-4(3H)-one (1.36?, 0
．． Bromine (1.5 ml, 0.03 mol) is added dropwise to a well-stirred mixture of 0.01 mol), sodium bicarbonate (2.52 f, 0.03 mol) and water (25 ml).

After stirring the mixture for 4 hours, the filtered solids were thoroughly washed with water and air-dried. The product (2.78r, 95%) was recrystallized from toluene-hexane (1:1) with a melting point of 210
A cream colored solid is obtained between 212°C and 212°C. Analysis: C5H
Calculated value as 2Br2N4O: C, 2O. 44;H,
O. 69;N, l9. lO; Br, 54.39; Actual value: C, l9. l6; H, O. 88;N, l8.8O;B
r, 54. l2. Example 37 8-bromoethyl-6-phenylimidazo[1,5-
d]-As-triazin-4(3H)-one production 8-
Methyl-6-phenylimidazo[1.11d]-As
-triazin-4(3H)-one (4.52f7, 0.
02 mol), N-promosuccinimide (3.92f7,
0.044 mol), benzoyl peroxide (0.24r, 0
．． 002 mol) and carbon tetrachloride (200 ml) is refluxed for 8 hours.

The reaction mixture is cooled and filtered, and the solid separated is washed with water and methylene chloride. Product (2.1?, 34.4%)
Recrystallization from nitromethane gives pale yellow crystals. Melting point 254°C to 256°C (decomposition). Analysis: Cl2H, Br
Calculated value as N4O: C, 47.24; H, 2.97
; N, l8.48; Br, 26.2O; Actual value: C, 4
7.5O; H, 3.2l; N, l8.48; Br, 25
．． 78; ▲ The combined washings are evaporated and the residue is recrystallized from nitromethane to further obtain the above product with a yield of 14.8%.

Example 38 3-Alkyl-8-methyl-6-phenylimidaso A
Preparation of s-[1,5-d]-triazine-4(8H)-one Method A 8-Methyl-6-phenylimidaso As-[1,5-
d] monotriazine-4(3H)-one (3.39f,0
．． Sodium methoxide (0.015 mol) to a solution of sodium methoxide (0.015 mol)
．． 81f, 0.015 mole) followed by the appropriate alkylating agent (ie, methyl iodide, allyl bromide, propargyl bromide, benzene chloride, dipropyl sulfate, and the like).

The reaction mixture was stirred at 20°C for 16 hours, heated to 40°C for 45 minutes, cooled and poured into a mixture of ice and dilute hydrochloric acid. The product is extracted from the above aqueous mixture with chloroform and the chloroform layer is evaporated to isolate the desired product. The product is purified by recrystallization from cyclohexane or cyclohexane-benzene or by silica gel column chromatography in chloroform.

Method B 3,8-dimethyl-6-phenylimidazo [manufactured by 1*
5-d]-As-triazin-4(3H)-one 8-methyl-6-phenylimidazo[1.51d]-As-triazin-4(3H)-one (1.13y, 0.005
dimethylformamide dimethyl acetal (0.73 ml) was slurried in benzene (25 ml).
1; δ=0.897, 0.005 mol) was gradually added.

The reaction mixture was stirred and refluxed for 24 hours, then cooled and filtered. ▲ Evaporate the liquid to obtain a 1.4f (100%) product. The yellow crystals obtained by recrystallization from methylcyclohexane were found to be exactly the same as the product obtained by method A (infrared, NMR). The compounds obtained by both the above procedures are shown in Table 7 below.

Preparation of [1,5-d]-As-triazine-4(3H) monothione 8-methyl-6-phenylimidazo[1,5
-d]-As-triazine-4(3H)-thione (3.
76y, 0.014 mol) in a sodium bicarbonate aqueous solution (125mj,
6.7%).

Dimethyl sulfate (1.85y, 0.0147mol) at room temperature
is added and the reaction mixture is stirred overnight (approximately 15-16 hours). The precipitated solid was filtered with F, thoroughly washed with water, and then dried (3
．． 84f7) is extracted with benzene. The benzene solution is evaporated to dryness and the remaining red solid is extracted with hexane. Evaporation of the hexane solution yields a tan solid (0.25f7). This yellowish brown solid is recrystallized from methanol 3* to obtain pale yellow crystals with a melting point of 194°C to 195°C. analysis:
Calculated value as Cl3Hl2N4S: C, 6O. 92;
H, 4.72, N, 2l. 86: Actual value: C, 6O. 3
l; H, 4.9O; N, 2l. 34 Reference Example 70 Preparation of Amidines Amidines used as starting materials for the production of imidaso-As-triazinones, prepared by known methods, are shown in Table 8 below.

Unless otherwise specified, it is in the form of hydrochloride. References are also shown in the table.

Reference Example 71 Cis and trans-4,5-dimethyl-2-m-tolyl-2-imidazoline-4,5-diol hydrochloride m-toluamidine hydrochloride (13.6 t, 0.0797 mol) in water (35 ml) Add 2,3-butanedione (7.3 ml, 0.084 mol) to the medium-cooled slurry and stir at room temperature for 15 minutes.

When the precipitated product was filtered and washed with acetone, the melting point was 135°C.
Product 12.2f is obtained at ~137°C. Analysis: Calculated value as Cl2Hl7N2O2Cl: Cl
56. l4; H, 6.67; N, lO. 9l;Cl,l
3.8l. Actual value: C, 55.92; H, 6.66; N
, lO. 94; Cl, l4. O9. Other 2-substituted cis- and trans-4-
5-Dimethyl-imidazoline-4,5-diol hydrochloride, its melting point and the difference from the above method are shown in Table 9 below.

Claims (1)

[Claims] 1. A compound represented by the following general formula, ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Here, X is divalent oxygen or divalent sulfur; R_1 is hydrogen,
Methyl, chlorine, bromine, iodine or bromoethyl; R_2 is hydrogen, alkyl (C_1 to C_4), cycloalkyl (
C_3 to C_6), methoxymethyl, bromine, benzyl,
Naphthyl, phenyl or monosubstituted phenyl (where the substituents are chlorine, methyl, alkoxy (C_1-C_3),
amino, dimethylamino or nitro); R_3 is hydrogen,
Alkyl (C_1-C_3), allyl, propargyl;
And R_4 represents hydrogen or alkyl (C_1 to C_3). 2 X is oxygen; R_1 is methyl, bromine or chlorine; R_2
is cycloalkyl (C_3-C_6), phenyl or m
-Tolyl; and R_3 and R_4 both represent hydrogen. 3. The compound of claim 1, wherein X is sulfur and R_1 and R_2 are both hydrogen. 4. The compound of claim 1, wherein X is oxygen, R_1 is methyl and R_2 is phenyl. 5. The compound of claim 1, wherein X is sulfur, R_1 is methyl and R_2 is phenyl. 6. The compound of claim 1, wherein X is oxygen and R_1 and R_2 are both methyl. 7. The compound of claim 1, wherein X is sulfur and R_1 and R_2 are both methyl. 8. The compound of claim 1, wherein X is oxygen, R_1 is bromine, and R_2 is phenyl. 9. The compound of claim 1, wherein X is sulfur, R_1 is methyl, and R_2 is benzyl. 10. The compound of claim 1, wherein X is oxygen, R_1 is chlorine, and R_2 is phenyl. 11. The compound of claim 1, wherein X is oxygen, R_1 and R_3 are both methyl, and R_2 is phenyl. 12 X is oxygen, R_1 is methyl, and R_2
A compound according to claim 1, wherein is n-propyl. 13 X is oxygen, R_1 is methyl, and R_2 is t-
The compound of claim 1 which is butyl. 14. The compound of claim 1, wherein X is oxygen, R_1 is chlorine, and R_2 is p-chlorophenyl. 15 X is oxygen, R_1 is methyl, and R_2 is m-
The compound of claim 1 which is tolyl. 16. The compound of claim 1, wherein X is oxygen, R_1 is iodine, and R_2 is phenyl. 17 X is oxygen, R_1 is methyl, and R_2 is p-
A compound according to claim 1 which is aminophenyl. 18. The compound of claim 1, wherein X is oxygen, R_1 is bromine, and R_2 is m-dimethylaminophenyl. 19 X is oxygen, R_1 is methyl, and R_2 is 2-
The compound of claim 1 which is naphthyl. 20 X is sulfur, R_2 is n-propyl; and R_1
, R_3 and R_4 are all hydrogen. 21. The compound of claim 1, wherein X is sulfur; R_1 is methyl; R_2 is n-propyl; and R_3 and R_4 are both hydrogen. 22 X is sulfur, R_2 is methyl, and R_1
, R_3 and R_4 are all hydrogen. 23. The compound of claim 1, wherein X is oxygen, R_1 is methyl, R_2 is phenyl, and R_3 and R_4 are both hydrogen. 24. The compound of claim 1, wherein X is oxygen, R_2 is n-propyl, and R_1, R_3 and R_4 are all hydrogen. 25. The compound of claim 1, wherein X is oxygen, R_1 and R_2 are both methyl, and R_3 and R_4 are both hydrogen. 26 X is oxygen, R_1 is methyl, and R_2
, R_3 and R_4 are all hydrogen. 27 X is oxygen, R_1 is methyl, R_2 is t-
The compound of claim 1, wherein butyl and R_3 and R_4 are both hydrogen. 28 X is oxygen, R_1 is methyl, R_2 is n-
The compound of claim 1, wherein propyl and R_3 and R_4 are both hydrogen. 29 X is oxygen, R_1 is methyl, R_2 is p-
The compound of claim 1, wherein chlorphenyl and R_3 and R_4 are both hydrogen. 30. The compound of claim 1, wherein X is oxygen, R_1 is methyl, R_2 is n-butyl, and R_3 and R_4 are both hydrogen. 31. The compound of claim 1, wherein X is oxygen, R_1 is hydrogen, R_2 is cyclopropyl, and R_3 and R_4 are both hydrogen. 32. The compound of claim 1, wherein X is oxygen, R_1 is hydrogen, R_2 is cyclohexyl, and R_3 and R_4 are both hydrogen. 33. The compound of claim 1, wherein X is oxygen, R_1 is bromine, R_2 is m-anilino, and R_3 and R_4 are both hydrogen. 34 X is oxygen, R_2 is m-nitrophenyl,
The compound according to claim 1, wherein R_1, R_3 and R_4 are all hydrogen. 35. The compound of claim 1, wherein X is oxygen, R_1 and R_2 are both bromine, and R_3 and R_4 are both hydrogen. 36. The compound of claim 1, wherein X is oxygen, R_1 and R_3 are both methyl, R_2 is phenyl, and R_4 is hydrogen. 37 X is oxygen, R_1 is methyl, R_2 is phenyl,
The compound of claim 1, wherein R_3 is allyl and R_4 is hydrogen. 38 X is oxygen, R_1 is methyl, R_2 is phenyl,
The compound of claim 1, wherein R_3 is propargyl and R_4 is hydrogen. 39 X is oxygen, R_1 is methyl, R_2 is phenyl,
The compound of claim 1, wherein R_3 is n-propyl and R_4 is hydrogen. 40 The following formula ▲ There is a mathematical formula, chemical formula, table, etc. ▼ or ▲ There is a mathematical formula, chemical formula, table, etc. ▼ {Here R is methyl or ethyl, and R_1
is hydrogen, methyl, chlorine, bromine, iodine or bromoethyl; R_2 is hydrogen, alkyl (C_1 to C_4), cycloalkyl (C_3 to C_6), methoxymethyl, bromine,
Benzyl, naphthyl, phenyl or monosubstituted phenyl [where the substituents are chlorine, methyl, alkoxy (C_1-
C_3), amino, dimethylamino or nitro]; and R_4 shall represent hydrogen or alkyl (C_1 to C_3)} in a non-polar high-boiling organic solvent to a temperature of 175 to 275 °C. The following general formula ▲ includes mathematical formulas, chemical formulas, tables, etc. ▼ (where X is divalent oxygen or divalent sulfur, and R_3
is hydrogen, and R_1, R_2 and R_4 are as described above. ) The method for producing the compound represented by 41 The following general formula▲ Numerical formulas, chemical formulas, tables, etc.▼ [Here, X is divalent oxygen or divalent sulfur;
_3 to C_6), methoxymethyl, bromine, benzyl, naphthyl, phenyl or monosubstituted phenyl, where the substituent is chlorine, methyl, alkoxy (C_1 to C_3),
amino, dimethylamino, or nitro); R_4 represents hydrogen or alkyl (C_1 to C_3)] in an inert solvent at 60 to 90°C.
The following general formula ▲mathematical formula, chemical formula, table, etc. is characterized by treatment with chlorine or bromine at a temperature of ▼ (where R_1 is chlorine or bromine, R_3 is hydrogen,
R_2 and R_4 are as described above). 42 The following general formula▲ Numerical formulas, chemical formulas, tables, etc.▼ [Here, R_1 is hydrogen, methyl, chlorine, bromine, iodine, or bromoethyl; R_2 is hydrogen, alkyl
C_4), cycloalkyl (C_3-C_6), methoxymethyl, bromine, benzyl, naphthyl, phenyl or monosubstituted phenyl (where the substituents are chlorine, methyl, alkoxy (C_1-C_3), amino, dimethylamino or nitro); R_4 is hydrogen or alkyl (C_1~
The following general formula ▲ There are mathematical formulas, chemical formulas, tables, etc.▼ (wherein R_3 is hydrogen, R_1, R_2 and R_4 are as described above). 43 The following general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ {Here, X is divalent oxygen or divalent sulfur; R_1 is hydrogen, methyl, chlorine, bromine, iodine, or bromoethyl; R
_2 is hydrogen, alkyl (C_1 to C_4), cycloalkyl (C_3 to C_6), methoxymethyl, bromine, benzyl, naphthyl, phenyl or monosubstituted phenyl [where the substituent is chlorine, methyl, alkoxy (C_1 to C_3]
), amino, dimethylamino or nitro]; and R_
4 represents hydrogen or alkyl (C_1 to C_3)] is treated with an alkali metal lower alkoxide in an inert solvent, and then the compound represented by the following general formula R_3-halogen [where R_3 is alkyl ( C_1 to C_3), allyl, or propargyl, and the halogen is chlorine, bromine, or iodine] at 20° to 40°C.
The following general formula ▲ is characterized in that it is added at a temperature of
There are mathematical formulas, chemical formulas, tables, etc. ▼ (here X, R_1,
R_2, R_3 and R_4 are as described above).