JPS6056711B2 - Synthesis method of imidazole dithiocarboxylic acid benzyl ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for synthesizing imidazole dithiocarboxylic acid benzyl ester, and specifically has the structural formula 3R4 total-SHN/NHsR.

[However, R in the formula.

A hydrogen atom or a residue selected from the group consisting of a methyl group, an ethyl group, an undecyl group, a heptadecyl group and a phenyl group, R, represents a hydrogen atom or a methyl group. It is characterized by causing a condensation reaction between the imidazoledithiocarboxylic acid shown in ] and a benzyl halide.

Structural formula R4 -s-℃H2O [However, in the formula, R2 and R4 are the same as above.

] This relates to a method for synthesizing benzyl imidazole dithiocarboxylic acid ester. It is known that imidazole dithiocarboxylic acid and its alkali metal salt, which are the starting materials for the method of the present invention, can be easily obtained in high yield from the corresponding parent imidazole and carbon disulfide, as shown in the following reaction formula. This has already been discovered by the present inventors. (Refer to JP-A-57-176965) When the starting material imidazoledithiocarboxylic acid and benzyl halide are subjected to a condensation reaction, the benzyl dithiocarboxylic acid ester hydrogen halide salt is first produced according to the following reaction formula 1. Then, the desired benzyl ester is obtained by reacting the hydrogen halide salt with a hydrogen halide acceptor. Further, when the starting material imidazoledithiocarboxylic acid and the benzyl halide are subjected to a condensation reaction in the presence of a hydrogen halide acceptor, the target benzyl ester is obtained according to the reaction formula shown below.

Further, when the starting material, an alkali metal salt of imidazole dithiocarboxylic acid, is subjected to a condensation reaction with a benzyl halide, the target benzyl ester can be obtained according to the following reaction formula.

The starting imidazoledithiocarboxylic acid alkali salts are primarily sodium and potassium salts.

When imidazole dithiocarboxylic acid is synthesized by reacting imidazole and carbon disulfide in the presence of alkali hydroxide, the alkali metal salt of the dithiocarboxylic acid is first produced.
It can be used as it is as a starting material for benzyl ester synthesis. Since the dithiocarboxylic acid easily forms a salt with the basic ion B4 to give the dithiocarboxylic acid B salt as shown in the following reaction formula, the B salt can also be used as a starting material.

The basic ion B1 used is Lil, Na.
4, K4, Cal4, Ball, Mgll, Znll,
Cull, Mnll, COllll, Nill, Fel4
4, Hgll, Sn44, Pb44, NH48, organic ammonium ions, etc.

As mentioned above, the dithiocarboxylic acid easily forms various salts with various metal ions, but the use of these metal salts as starting materials is economically disadvantageous compared to the use of sodium and potassium salts. I can't think of any particular advantage.

The hydrogen halide acceptor used in the present invention is of a very general type, and any acceptor can be used as long as it reacts with hydrogen halide to give a neutralized salt.

They are as shown below. NH3, NH4OH,
LiOH, NaOH, KOH, Ca(0H)2, Ba(
0H)2, Mg(0H)2, Li2C0,,1(2C0
39cac039Bac039Mgc039CH3C0
Tertiary amines such as 0Na, CH3C00K, Et3N and pyridines, quaternary ammonium hydroxides (eg TritOnB9) and the like.

The benzyl halides used in the present invention include benzyl chloride, benzyl bromide, and benzyl iodide, but benzyl iodide is considered to be too expensive and less practical than the former two.

Considering the reaction between the active hydrogen in the solvent and the benzyl halide, theoretically it would be desirable for the solvent used in the reaction to have no active hydrogen, but experimental results do not necessarily suggest that such a prediction is accurate. It has been found that solvents such as water and alcohol can also be used satisfactorily.

Therefore, restrictions regarding solvents are not considered to have much significance. Representative solvents suitable for the practice of this invention include water, methyl alcohol, ethyl alcohol, disimethylformamide, dimethyl sulfoxide, acetonitrile, pyridine, acetic acid, acetone, and the like. The reaction of the present invention is exothermic.

Therefore, cooling is required at the start of the reaction, and after the reaction has progressed to a certain extent, the heat generation weakens, so heating is required.
This is a method of temperature control when shortening the reaction time is taken into consideration. In this case, the reaction temperature may be maintained between room temperature and 80°C. The reaction in this case is completed within about 2 hours. A reaction temperature of 8 crc or higher is not particularly required.

8 (generations) or less is sufficient.

In order to slow down the heat generation, it is desirable to drop a benzyl halide into the reaction system. It is of course possible to carry out the reaction for a long time under ice cooling or at room temperature unless shortening the reaction time is taken into account. The reaction apparatus must be equipped with a stirrer and a reflux condenser, but since these reactions proceed at normal pressure, there is no need to apply additional pressure.

Regarding the molar equivalent relationship of imidazole dithiocarboxylic acid or its alkali metal salt, benzyl halide, and hydrogen halide acceptor, 1 molar equivalent or more than 1 molar equivalent per 1 molar equivalent of the starting material dithiocarboxylic acid or its salt. A benzyl halide and a receptor may be used.

However, it is uneconomical and meaningless to use them in gross excess. Isolation and purification of the target product is carried out according to conventional methods.

Specific aspects thereof will be described later in Examples. Various imidazoledicarboxylic acid benzyl esters obtained by the method of the present invention are useful as epoxy resin curing agents, curing accelerators, agricultural chemical intermediates, and pharmaceutical intermediates. Next, the properties of the starting material and the target product will be illustrated.

1 Imidazole dithiocarboxylic acid sodium salt [Both have high melting points and it is difficult to indicate the melting point based on normal melting point measurement.

Instead, Rf at L°C (Silica G, .EtOH) is displayed. ] Imidazole-4-dithiocarboxylic acid Na salt Rf: 0.0 (derived from Na, B.T.B), 0.45~
0.60 (visual observation) 2-methylimidazole-4-dithiocarboxylic acid Na salt Rf: 0.0 (derived from Na, B.T.
B color), 0.50 to 0.60 (visual observation) 2-ethylimidazole-4-dithiocarboxylic acid Na salt Rf: 0.0 (B
．． T. B), 0.63-0.77 (visual observation) 2-undecylimidazole-4-dithiocarboxylic acid Na salt Rf: 0
．． 0 (B.T.B), 0.57 to 0.70 (visual) 2-
Sodium heptadecyl imidazole-4-dithiocarboxylate
Salt Rf: 0.0 (B.T.B), 0.63 to 0.75 (
Visual observation) 2-phenylimidazole-4-dithiocarboxylic acid Na salt Rf: 0.0 (B.T.B), 0.52 to 0.
66 (visual observation) 4-methylimidazole-5-dithiocarboxylic acid Na salt Rf: 0.0 (B.T.B), 0.44~
0.58 (visual observation) 2.4-dimethylimidazole-5-dithiocarboxylic acid Na salt Rf: 0.0 (B.T.B),
0.55-0.68 (visual observation) 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid Na salt Rf: 0.0
(B.T.B), 0.60-0.73 (visual observation) 2-undecyl-4-methylimidazole-5-dithiocarboxylic acid Na salt Rf: 0.0 (B.T.B), 0.78-0.
90 (visual observation) 2-phenyl-4-methylimidazole-5-dithiocarboxylic acid Na salt Rf: 0.0 (B.T.B
), 0.62 to 0.74 (visual observation) Each of the above Na salts exhibits strong νc=s absorption at 950 to 103h-1.

Imidazole dithiocarboxylic acid Imidazole-4-dithiocarboxylic acid: Reddish brown crystals.

neutral. M. p. 157-15 (1jC0 dissolved in water, methanol, chloroform, acetone, acetic acid.

D ■ TDMSOI easily soluble in NaOH aqueous solution.

Rf: 0.45-0.60 (visual observation). νU′. 1:14
38 (second absorption), 1025 (first absorption).

NMR (DMSO-D6): δ8.8D,. lH;7
．． 78, DllHMass:m/El44(M+), 1
11 (M-SH), Seki (imidazole), 44 (:C=
S) 2-methylimidazole-4-dithiocarboxylic acid:
Reddish-brown crystals.

neutral. M. p. 187-188°C.

Slightly soluble in water, methanol, chloroform, acetone, acetic acid, acetonitrile, and pyridine. DMSO,. DMF'.
．． Easily soluble in NaOH aqueous solution. Rf:0.50-0.60(
Visually). νU′. 1:1607 (3rd absorption), 1210
(first absorption), 1040 (third absorption). NMR (DMF
-D7): δ7.75, SllH; 2.67, S. ．． 3
HMass: m/El58 (M+), 125 (M+-S
H), 81, 7fK44 (:C=S) 2-ethylimidazole-4-dithiocarboxylic acid: reddish brown crystals.

neutral. M. p. 137~13CfC0 Slightly soluble in water, chloroform, and acetic acid.

Methanol, DMSO, . Easily soluble in NaOH aqueous solution. Rf
:0.64-0.77 (visual observation). νUr. l:1605
(second absorption), 1045 (first absorption). NMR (DMS)
O-D6): δ7.70ss11H: 2.87, Q, .
2H; 1.2 tons T,. 3HOMass:m/El72(
M, 139 (M+-SH), 96s95s442-undecylimidazole-4-dithiocarboxylic acid: brown crystals.

neutral. M. p. ll6-119.

Slightly soluble in C0 water, chloroform, and cold acetic acid. Soluble in methanol, acetone and hot acetic acid. DMSO. ．． Easily soluble in NaOH aqueous solution. Rf: 0.70 to 0.81 (visual observation). νU
Al: 1602 (4th absorption), 1205 (3rd absorption),
1042 (first absorption). NMR (CF3COOH)
δ7.98, SllH3. lO, T. ．． 2H; 1.88
,M,. 2H; 1.30, M, 16H; 0.87, M,
．． 3HOMass: m/E298 (M two, 265 (M+
-SH), 2,223s442-heptadecyl imidazole-4-dithiocarboxylic acid: brown crystals. neutral. M.
p. 1O7~1177C0 Slightly soluble in water, chloroform, and cold acetic acid.

Soluble in DMSO. Rf: 0.63 to 0.75 (visual observation).
νu1: 1600 (first absorption), 1525 (third absorption)
, 1040 (second absorption). NMR (DMSO-D6):
δ7.70, SllH; 2.80, M,. 2H; 1.6
5, m1? ;1.22, Ml28H;0.8\M. ．． 3
HOMass: m/EM+ does not appear, 348 (M+-H
2S), 33tons 317, 307, 30dens 442-phenylimidazole-4-dithiocarboxylic acid: brown crystals. Mild acidity. M. p. 154-157°C.

Slightly soluble in water, methanol, chloroform, acetic acid, and acetone. Easily soluble in DMSO1NaOH aqueous solution. Rf: 0.52~
0.66 (visual). νU'-1: 1615 (second absorption)
, 1215 (first absorption), 1040 (first absorption). N.M.
R (DMSO-D8): δ8.33s to 7.92, M.
．． 2H; 7.92, SllH; M. to 7.76-7.3.
．． 3HOMass: m/E22O(M+), 187(M
+-SH), 14 Table 10t77. 4-Methylimidazole-5-dithiocarboxylic acid: Reddish brown crystals.

neutral. M. p. 159-161°C.

Slightly soluble in water, methanol, chloroform, and acetic acid. DMSO
Easily soluble in NaOH aqueous solution. Rf: 0.47-0.60 (
Visually). νUr. l:1590, 1440, 1375,
1265, (2nd absorption), 1120s1020s92 飄86 to 80 to 720. M interpretation (DMSO-D6): δ&6
0, SllH; 2.62, S1 aim. Mass:m/El
58 (M, 125 (M+-SH), 81, 7ePS4
42.4-Dimethylimidazole-5-dithiocarboxylic acid: Red crystals.

M. p. 187-189zoC0 Slightly soluble in water, methanol, ethanol, chloroform, and acetone.

Soluble in acetic acid. DMF. ．． Easily soluble in DMSO. Rf: 0.5
7 to 0.70 (visual). νUr. l: 1615 (second absorption), 1025 and 990 (first absorption).

NMR (CF3COOH) δ2.77, S1 aim; 2.
70,. s. ．． 3H0Mass:m/El72(M+)
, 139 (M+-SH), 9\422-ethyl-4-methylimidazole-5-dithiocarboxylic acid: reddish-purple crystals.

neutral. M. p. l77~17CfC0 water, methanol,
Slightly soluble in ethanol and acetone. Soluble in acetic acid. DMF,.
Easily soluble in DMSO. Rf: 0.60 to 0.70 (visual observation).
νU′. 1:1615 (second absorption), 1013 (first absorption).

NMR (DMSO-D6): δ2.80. q. 2H:2
．． 60, S. s3H:1.2\T. ．． 3HOMass:
m/El86 (M, 153 (M+-SH), 1 bird, 1
092-Undecyl-4-methylimidazole-5-dithiocarboxylic acid, red solid.

basic. M. p. Unable to measure due to high moisture absorption. water, methanol,
Soluble in ethanol. Rf: 0.70-0.80 (visual observation)
. νU′. 1:1512 (first absorption), 1378 (second absorption)
absorption), 1000 (third absorption). Mass: m/E3l
2 (M, 279 (M+-SH), 247 (N'-HS
2) 23602-phenyl-4-methylimidazole-5-dithiocarboxylic acid: reddish brown crystals. M. p. l65～
168℃. Slightly soluble in water, methanol, ethanol, acetone, chloroform, t-butanol, and benzene. acetic acid,
Soluble in methyl cellosolve. DMF. ．． DMSO. ．． Na
Soluble in OH aqueous solution.

Rf: 0.65-0.780νU'. 1:1625 (third absorption), 1603, 1540, 1485, 1215 (
2nd absorption), 1040 (1st absorption).

NMR (CF3COOH) δ8.00, ~7.50,
m1 station; 2.89, S,. 3HOMass:m/E23
4 (M, 201 (M+-SH), 1 Seki, 10 tons 77.
Target product Benzyl ester f midazole-4-dithiocarboxylic acid-benzyl ``Stell i'' Physical properties: Orange crystals.

neutral. M. p. 144-146°C (acetone). Insoluble in ice. Soluble in methanol, ethanol, acetone, acetic acid, chloroform, and benzene.・L℃(Silica G..EtO
H): RfO. 6O to 0.70 (12 colors). ●ν day R
．． l:1046 (νC=S1 first absorption) ●NMR (CF
3COOH): δ&79sS11H (proton at 2nd position);
8.03, SllH (4th position proton) 7.3eKS,.
5H (phenyl proton); 4.67, Sl2H (methylene proton of benzyl).

・Mass: m/E234 (M, 201 (M+-SH
), 143 (Im+CS2), 111 (Im+CS),
91, 77.

2-Methylimidazole-4-dithiocarboxylic acid monobenzyl ester Structural formula Physical properties Orange crystals.

neutral. M. p. l34-136 BoC (acetone), poorly soluble in water. Soluble in methanol, ethanol, acetone, acetic acid, chloroform, and benzene. ●TLC (Silica G,.E
tOH,. l2): RfO. 6O~0.70νUr. l
:1075 and 1063 (νC: S1 first absorption).・N
MR (CF3COOH): δ7.85. s11H (4th position proton); 7.33, S, . 5H (phenyl proton); S. to 4.7. ．． 2H (methylene proton of benzyl); 2.7 minS. ．． 3H (methyl).

●Mass: m/E248 (M, 215 (M+-SH
), 157 (Im+CS2), 125 (Im+CS),
91, 44 (:C=S).

2-ethylimidazole-4-dithiocarboxylic acid benzyl ester Structural formula Physical properties Orange crystals.

neutral. M. p. 134-136°C (acetate). Poorly soluble in water. Soluble in methanol, ethanol, acetone, acetic acid, chloroform, and benzene. ●TLC (Silica G, .EtO
H,. l2): RfO. 68-0.78・v duck R. l:
1047 (νC=S1 first absorption).

・NMR (CF3COOH) δ7.89, SllH
(4th place); 7.32, S,. 5H (phenyl); 4.6
4, Sl2H (methylene); 3.13sq,. 2H (methylene of ethyl); 1.4&St. ．． 3H (methyl).
●Mass: m/E262 (M, 229 (M+-SH
), 171 (Im+CS2) 139 (Im+CS), 9
1,77, female 2-undecylimidazole-4-dithiocarboxylic acid benzyl ester Structural formula Physical properties Orange crystals.

neutral. M. p. 55-Kan (acetone). Poorly soluble in water. Soluble in methanol, ethanol, acetone, chloroform, acetic acid, toluene, and benzene.・TLC (Silica G.
．． EtOH,. l2): RfO. 75~0.8s0●i
distribution: 1059 (νC=S1 first absorption).

●NMR (CF3COOH) δ7.86, SllH
(4th place): 7.32, SN5H (phenyl): 4.64
, Sl, 2H (benzyl methylene); Tl2 to 3.1
H (α-methylene); 1.88, M, . 2H (β-methylene); 1.30, Mll6H (intermediate polymethylene);
0.87, M. ．． 3H (terminal methyl).・Mass: m
/E388(M, 355(M+-SH), 297)(
Im+CS2), 265 (Im+CS), 91, female 2-heptadecyl imidazole dithiocarboxylic acid benzyl ester Structural formula Physical properties Orange crystal.

neutral. M. p. 63-7C) C (acetone). Poorly soluble in water. Soluble in methanol, ethanol, acetone, acetic acid, chloroform, and benzene.・TLC (Silica G, .EtO
H. ．． l2): RfO. 77~0.88・νduck′. 1:
1057 (first absorption).

・NMR (CF3COOH) δ7.88, SllH
(4th place); 7.33. S11H (phenyl); 467,
S... 2H (benzyl methylene); 3.11, T, .
2H (α-methylene); 1.90, M. ．． 2H (β-methylene); 1.32, Ml28H (intermediate polymethylene)
:0.89, M,. 3H (terminal methyl). ●Mass:
m/E472 (M, 439 (M+-SH), 381 (
Im+CS2), 349(Im+CS), 91.

2-phenylimidazoledithiocarboxylic acid benzyl ester Structural formula Physical properties Orange crystal.

neutral. M. p. 149-151°C (acetone). Poorly soluble in water. Methanol, ethanol, acetone, acetic acid, DMS
Soluble in O. ●TLC (Silica G,.EtOH..l2)
:RfO. 65～0.750●ν鵠R. l:1510S
76\720 to 1481, 107.

●NMR (CF3COOH) δ&03, SllH(
4th place), &00-7.80, Ms2H (phenyl): 7
．． 80~7.50sm,. 3H (phenyl); 7.34
sS15H (benzyl phenyl): 4.68, S. ．．
2H (benzyl methylene). ●Mass: m/E3l
O(M, 277(M+-SH), 219(Im+CS)
2), 187 (Im+CS), 104s91, 77, 4
44-methylimidazole dithiocarboxylic acid benzyl ester Structural formula Physical properties Orange crystals.

neutral. M. p. 144-147°C (acetone). Poorly soluble in water. Soluble in methanol, ethanol, acetone, acetic acid, chloroform, and benzene. ．． TLC (Silica GSEtO
Hl■2): RfO. 56-0.67·νUr. l:1
050 (first absorption).・NMR (CF3COOH)
δ & 0, SllH (2nd place); 7.37, S, . 5H (phenyl); 4.71, Sl2H (benzylamethylene)
;2.84sS,,3H (methyl).

●Mass: m/E248 (M, 215 (M+-SH
), 157 (Im+CS2), 125 (Im+CS),
91,4402.4-Dimethylimidazole dithiocarboxylic acid benzyl ester Structural formula Physical properties Orange crystals.

neutral. M. p. 152-154°C (acetone). Poorly soluble in water. Soluble in methanol, ethanol, acetone, acetic acid, chloroform, and benzene. ●TLC (Silica G,.Et
OH,. l2): RfO. 65-0.750●ν duck R.
l:159 to 1521, 1375, 105λ1020 (
1st absorption), 6890●NMR (CF3
COOH): δ7. Otori S1 cane (phenyl); 4.67,
S. ．． 2H (benzyl methylene); 2.76, S. ．．
3l ((2nd methyl); 2.72, Sl3H (4th methyl).

●Mass: m/E262 (M, 299 (M+-SH
), 171 (Im+CS2), 139 (Im+CS),
91,4402-Ethyl-4-methylimidazoledithiocarnoboxylic acid benzyl ester Structural formula Physical properties Yellow-orange crystals.

neutral. M. p. lO9-111°C (acetone). Poorly soluble in water. Soluble in methanol, ethanol, acetone, acetic acid, chloroform, carbon tetrachloride, benzene, and toluene. ●T
LC (Silica GlEtOH..l2): RfO. 68~
0.78・νUr. l:158 to 1523 ((first absorption), 1390s1040 (second absorption), 838.703
．． -NMR (CDCl3): δ7.30, M. ．． 5H (
phenyl); 4.57, S. ．． 2H (benzyl methylene) 2.6 gsq,. 2H (α-methylene); 2. Seki,
S1 target (4-position methyl); 1.29,t,3H (terminal ethyl).

・Mass: m/E276 (M+), 243 (M+-S
H), 185 (Im+CS2), 153 (Im+CS)
, 91. 2-Undecyl-4-methylimidazole dithiocarboxylic acid benzyl ester Structural formula Physical properties Red viscous liquid.

Neutral, poorly soluble in water. Soluble in methanol, ethanol, chloroform, acetic acid, benzene, and toluene. ●TLC (Silica G1 chloroform to methanol volume ratio 1 (7) 1):
RfO. 7O~0.80.

・ν distribution: 1520.1390.1050 (second absorption).・NMR (CF3COOH) δ7.36sS,
．． 5H (phenyl): 469sS,. 2H (benzyl methylene); 3.07, T. ．． 2H (α-methylene);
2.77, S1 target (4th methyl); 1.87, M, . 2
H (β-methylene): 1.32, Mll6H (intermediate polymethylene) 0.89. m. ．． 3H (terminal methyl).・M
ass: m/E4O2 (M, 369 (M+-SH),
311 (Im+CS2), 2790m+CS), 91,
4402-Phenyl-4-methylimidazole dithiocarboxylic acid benzyl ester HCl salt Structural formula Physical properties Red-orange crystal.

Acidic. M. p. 88-95°C (acetic acid). water, acetone,
Poorly soluble in toluene. Soluble in methanol, ethanol, acetic acid, and chloroform. ●TLC (Silica G..EtOH..
l2): RfO. 7l~0.80vU'. 11055(
1st absorption) NMR (CF, COOH): δ8.10-7
．． M to 8. 2H (phenyl); M to 7.80-7.5
．． ．． 3H (phenyl); 7.37, S, . 5H (phenyl); 4.72, S, . 2H (benzyl methylene)
;2.9 to S. ．． 3H (methyl).

・Mass: m/E324 (M, 291 (M+-SH
), 233 (Im+CS2), 201 (Im+CS),
10 Table 91, 77, Imperial Rescript, Example 1 A reaction vessel equipped with a reflux condenser was mounted on a magnetic stirring hot plate, and 2 ml of DMFL and 0.03 mol (4
．． 32'), added 0.03 mol (3.8 V) of benzyl chloride at room temperature, and heated at 40-45°C for 1 hour.
The reaction was carried out at 5 to 80°C for 1 hour, and the contents were concentrated under reduced pressure to obtain a candy-like residue.

Methanol was added to the residue to remove insoluble materials, and the liquid was made ammoniacal and concentrated under reduced pressure. The resulting residue was boiled with water, cooled, and the aqueous layer was decanted (water-soluble components was removed by water extraction) to give a candy-like residue. This solidified by standing. A hot acetone solution of the solidified product was treated with activated carbon to remove crystals that precipitated from the solution when cold, and then the crystals were reconsolidated twice with acetone to obtain M.I. p. l44~14
1.2f of imidazole-4-dithiocarboxylic acid monobenzyl ester at 6°C was obtained and used as an identification sample. Example 2 12 wLt of ethanol and 0.03 mol (4.32') of imidazole-4-dithiocarboxylic acid were added to the reactor of Example 1.
) and 0.03 mol (5.13 f) of benzyl bromide.
was added, the reaction was carried out for 2 hours in the same manner as in Example 1, the contents were cooled and filtered, and the liquid was made basic with aqueous ammonia and then concentrated under reduced pressure to form a solid residue.
After recrystallization with water in Step 1, recondensation with acetone was performed to obtain crude imidazole-4-dithiocarboxylic acid benzyl ester [M. p
．． l4O~145°C: T pressure (Silica G, chloroform to methanol volume ratio 10:1, 12) RfO. 3O~0.
40; 5.6y (79% yield based on dithiocarboxylic acid) was obtained.

Example 3 2-methylimidazole-4-dithiocarboxylic acid 0.0
3 mol (4.74y), benzyl chloride 0.03 mol (3
．． 8y) and dimethylformamide (DMF') 12m
1 were reacted in the same manner as in Example 1, and the crystals precipitated by cooling were collected from the system, washed with 20 ml of acetone, and further reconsolidated twice with ethanol to obtain crystals 3.9y. .

Next, the methanol solution of the crystals was made basic with aqueous ammonia and then dried under reduced pressure. The dried product was boiled with water, cooled, and the aqueous layer was decanted to obtain a candy-like residue. This solidified by standing and was reconsolidated twice with acetone to obtain M. p
．． 2-Methylimidazole-4-dithiocarboxylic acid benzyl ester 21f at a temperature of 34 to 136°C was obtained and used as an identification sample.

Example 4 0.03 mol of 2-methylimidazole dithiocarboxylic acid, 0.03 mol of benzyl chloride, 1.82y of 28% ammonia water (0.03 mol in terms of ammonia), and 12ml of water.
4 were reacted in the same manner as in Example 1, the system was cooled, the aqueous layer was decanted, 30 ml of water was added to the residue, boiled and cooled, the aqueous layer was decanted again and a candy-like residue was obtained. And so.

The residue was reconsolidated with ethanol to obtain crude 2-methylimidazole dithiocarboxylic acid benzyl ester [M. p. l2
O~1300C; TLC (same as Example 2) RfO. 4
2-0.52, 0.75-0.80 (light) 3.7'
(50% based on dithiocarboxylic acid)] was obtained. Example 52 - 0.03 mol of methylimidazole dithiocarboxylic acid, 0.03 mol of benzyl chloride, 0.015 mol of potassium carbonate, and 12 ml of water are reacted in the same manner as in Example 1, and precipitated from the reaction system when cold. Take the crystals and store them in 50m1
After boiling with water, cooling and removing the aqueous layer, the residue was reconsolidated with acetone to obtain crude 2-methylimidazole dithiocarboxylic acid benzyl ester [M. p. l28~132℃; TL
C (same as Example 2) RfO. 45-0.55; 5.1
y (yield of tin relative to dithiocarboxylic acid %)] was obtained.

Example 6 2-methylimidazole dithiocarboxylic acid 0.03 mol, benzyl chloride 0.03 mol Sodium acetate trihydrate 0
．． 03 mol (4.1y) and 20 ml of water were reacted in the same manner as in the above example, the aqueous layer was removed when cooled, acetone was added to the residue, it was filtered, an acetone solution was collected, and it was dried under reduced pressure. The solidified and dried product was reconsolidated with acetone to obtain 2-methylimidazole dithiocarboxylic acid monobenzyl ester [M. p.
123-130'C; L°C (same as Example 2) RfO.
45-0.55, 0.77-0.80 (very thin);
3.9V [yield of 52% based on dithiocarboxylic acid] was obtained.

Example 7 0.03 mol of 2-methylimidazole dithiocarboxylic acid, 0.03 mol of benzyl chloride, 12 ml of acetonitrile
The three components were reacted in the same manner as in the previous example, and the crystals precipitated when cold were filtered out, dissolved in 40 ml of water, filtered once, the resulting solution was made sufficiently basic with potassium carbonate, and the aqueous layer was decanted to remove the remaining residue. The product was reconsolidated with acetone to obtain crude 2-methylimidazole dithiocarboxylic acid benzyl ester [M. p. l28-13
3'C; TLC (same as Example 2) RfO. 45-0.
55:2.8y (yield G% relative to dithiocarboxylic acid)].

Example 8 0.03 mol of 2-methylimidazole dithiocarboxylic acid, 0.03 mol of benzyl chloride, and 2 ml of DMF1 were reacted in the same manner as in the previous example, and the crystals precipitated from the cold system were collected and washed with acetone. Ethanol recondensation yields the target hydrochloride salt, which is dissolved in methanol and sufficient aqueous ammonia is added. The methanol solution is dried under reduced pressure. It was extracted and removed in the same manner, and the extraction residue was reconsolidated with acetone to give crude 2-methylimidazole dithiocarboxylic acid benzyl ester [M. p
．． l34-13 (generation); TLC (same as Example 2) Rf
O. 45-0.55:3.3f (44% yield based on dithiocarboxylic acid)].

Example 9 2-ethylimidazole-4-dithiocarboxylic acid 0.03 mol (5.16 V), benzyl chloride 0.03
Mol (3.80 g) and 2 ml of DMF1 were reacted in the same manner as in the previous example, the contents were dried under reduced pressure, the dried product was washed with acetone, and then recrystallized twice with ethanol to obtain the crystals. Dissolved in hot ethanol and treated with activated carbon,
4.4 fI of crystals precipitated from the resin solution during cooling were collected.

The crystals were dissolved in methanol and made basic with aqueous ammonia, then dried to dryness under reduced pressure, and the dried product was recrystallized with water to form crystals. The crystals are dissolved in hot acetone and treated with activated carbon, and the crystals that precipitate from the liquid are taken out when cold.
After reuniting, M. p. 1.8 f of 2-ethylimidazole-4-dithiocarboxylic acid benzyl ester at a temperature of 34 to 136°C was obtained and used as an identification sample. Example 10 2-methylimidazole-4-dithiocarboxylic acid 0.0
3 mol, benzyl chloride 0.03 mol and DMF'121
! The three components of Lt were reacted in the same manner as in the above example, the contents were dried to dryness under reduced pressure, and the dried product was washed with acetone and recondensed with ethanol to obtain the hydrochloride.

After dissolving this product in hot methanol and adding sufficient aqueous ammonia, the methanol solution was dried under reduced pressure, and the water-soluble components in the dried product were extracted and removed with 50 ml of water in the same manner as in Example 1. was reconstituted with acetone to obtain 2-methylimidazole-4-dithiocarboxylic acid-benzyl ester [M.
p. l34-136°C; TLC (same as Example 2) Rf
O. 56-0.66; 3.2f (40% yield based on dithiocarboxylic acid)].

Example 11 2-Undecylimidazole-4-dithiocarboxylic acid 0.03 mol (8.94y), benzyl chloride 0
．． 03 mol (3.8 f) and 2 ml of DMF1 were reacted in the same manner as in the previous example, and the reaction mixture was concentrated under reduced pressure to obtain a residue.

Methanol was added to the residue and filtered, and the residue was passed through a basic ion exchange resin layer (IRA-410) to remove the adsorbed matter.
Desorption was performed with Cl methanol, and the desorption solution was dried under reduced pressure. The dried product was dissolved in ethanol to make it basic with ammonia and dried under reduced pressure.The water-soluble components in the dried product were extracted with water in the same manner as in Example 1, and the acetone solution of the extraction residue was passed through a layer of activated clay. The first red solution was collected and concentrated to give a candy-like residue. When the candy-like residue is left to stand, it eventually solidifies and is reconstituted with acetone to give 0.6 fI of 2-undecylimidazole-4-dithiocarboxylic acid monobenzyl ester.
This was used as the identification sample. Example 12 2-undecylimidazole-4-dithiocarboxylic acid 0
．． 03 mol, benzyl chloride 0.03 mol, methanol 1
2r! Lt and NaOHO. 4 of O3 moles (1.2f)
The reaction mixture was concentrated in vacuo to give a residue.

After water-soluble components in the residue were removed by water extraction in the same manner as in Example 1, the extracted residue was dissolved in toluene, passed through a layer of activated clay, the effluent was dried, and the dried substance was reconsolidated with acetone to obtain a crude −
Undecylimidazole-4-dithiocarboxylic acid-benzyl ester [M. p. 5l-59boC; TLC (same as Example 2) RfO. 7O ~ 0.80, ~ 0.84 (very thin); 3.8f (yield 32% based on dithiocarboxylic acid)
)] was obtained. Example 13 2-heptadecylimidazole-4-dithiocarboxylic acid 0.01 mol (3.82f),
0.03 mol of benzyl chloride and 2 ml of DMF1 were reacted in the same manner as in the above example, and the reaction mixture was filtered in the cold.
The extract was dried under reduced pressure, and the dried product was dissolved in hot ethanol and treated with activated carbon.

The extract was dried under reduced pressure, and the dried product was reconstituted twice with ethanol.
The crystals were dissolved in methanol to make them ammoniacal and dried under reduced pressure.The water-soluble components in the dried product were removed by water extraction in the same manner as in Example 1 to obtain an extracted residue. This solidified substance was left to stand, and the solidified substance was dissolved in hot acetone and treated with activated carbon, the liquid was dried to dryness, and the crystals were reconsolidated with acetone. .1f was obtained and this was used as the identification sample. Example 14 2-undecylimidazole-4-dithiocarboxylic acid 0.01 mol, benzyl chloride 0.01
mol, 0.005 mol (0.5y) of calcium carbonate, and 2 ml of DMF1 were reacted in the same manner as in the previous example,
The reaction mixture was filtered when cold, the p liquid was dried under reduced pressure, the water-soluble components in the dried product were extracted and removed with 50 ml of water in the same manner as in Example 1, and the extracted residue was reconsolidated with acetone to obtain crude 2 -Undecylimidazole-4-dithiocarboxylic acid monobenzyl ester [M. p. 4O-55°C; TLC (same as Example 2) RfO. O8 ~ 0.01 (extremely thin), 0.77 ~
0.86, ~0.90 (extremely thin): 4.0' (yield % relative to dithiocarboxylic acid)].

Example 15 2-phenylimidazole-4-dithiocarboxylic acid 0.
03 mol (6.6f), benzyl chloride 0.03 mol and 2 ml of DMF1 were reacted in the same manner as in the above example,
Reaction contents after cooling? After filtration, the honeycomb solution was concentrated under reduced pressure to obtain a candy-like substance.

The candy-like substance was converted into a methanol solution with hydrochloric acid and concentrated under reduced pressure to obtain a candy-like residue. After several days, this solidified and was reconsolidated three times with ethanol. The crystals were dissolved in an ammoniacal methanol solution and concentrated under reduced pressure to obtain a residue. The water-soluble components in the residue were purified in the same manner as in Example 1. The extracted residue was dissolved in a hot acetone solution and treated with activated carbon, and the crystals precipitated from the solution were collected to obtain 2-phenylimidazole-4-dithiocarboxylic acid-benzyl ester.
7y was obtained and used as an identification sample. Example 16 2-phenylimidazole-4-dithiocarboxylic acid 0.
03 mol, benzyl chloride 0.03 mol, triethylamine 0.03 mol (3.04y) and ethanol 10 ml
The reaction mixture was concentrated under reduced pressure, the water-soluble components in the residue were extracted and removed with 50 ml of water in the same manner as in Example 1, and the extracted residue was reconsolidated with ethanol to obtain crude 2 -Phenylimidazole-4-dithiocarboxylic acid-benzyl ester [M. p. l35-145°C; T pressure (same as Example 2) RfO. 68-0.77, 0.80-0
．． 82 (extremely thin); 8.8y (yield 94% based on dithiocarboxylic acid)].

Example 17 4-methylimidazole-5-dithiocarboxylic acid 0.0
3 mol (4.74y), 0.03 mol of benzyl chloride and 2 ml of DMF1 were reacted in the same manner as in the above example,
The crystals precipitated from the reaction mixture when cold are taken off the coast, washed with acetone to obtain crystal 6.1f, the crystals are dissolved in a hot ethanol solution and treated with activated carbon, and precipitated from the resulting p liquid when cold. 3.9y of crystals were collected.

Next, the ammoniacal methanol solution of the crystals was dried under reduced pressure, the crystals were further recrystallized with water, the hot acetone solution of the crystals was treated with activated carbon, and the crystals precipitated when cold were collected from the resulting solution. This was further reconstituted with acetone to obtain 1.4y of 4-methylimidazole-5-dithiocarboxylic acid benzyl ester, which was used as an identification sample. Example 18 4-methylimidazole-5-dithiocarboxylic acid 0.0
3 mol, benzyl chloride 0.03 mol and pyridine 12 m
1 were reacted in the same manner as in Example 1, the reaction mixture was dried under reduced pressure, the water-soluble components in the dried product were extracted and removed with 50 ml of water in the same manner as in Example 1, and the extracted residue was re-extracted with acetone. The resulting crude 4-methylimidazole-5-dithiocarboxylic acid benzyl ester [M. p. l3l~138-C; TlC
(Same as Example 2) RfO. 4O~0.50s0.82
~0.85 (extremely thin); 4.7 g (yield based on dithiocarboxylic acid: 63%)] was obtained.

Example 19 0.03 mol (5.16f) of 2.4-dimethylimidazole-5-dithiocarboxylic acid, 0.03 mol of benzyl chloride and 2 ml of DMFL were reacted in the same manner as in the previous example, the system was cooled, and the precipitated crystals were collected. , washed with acetone to form crystals (7
．． 4g), which was further recrystallized twice with ethanol to obtain crystals 5.5y.

Next, the crystals were dissolved in an ammoniacal methanol solution and concentrated under reduced pressure, and the resulting residue was used in Example 1.
Water extraction was carried out in the same manner as above, and the extraction residue was diluted with acetone for 3 minutes.
Reconsolidation yielded 2.0y of 2.4-dimethylimidazole-5-dithiocarboxylic acid benzyl ester, which was used as an identification sample. Example 20 0.03 mol of 2.4-dimethylimidazole-5-dithiocarboxylic acid, 0.03 mol of benzyl chloride, 0.015 mol (1.11y) of calcium hydroxide, and 12 ml of methanol were added in the same manner as in the previous example. The reaction mixture was dried under reduced pressure, the water-soluble components in the dried product were extracted and removed with 50 ml of water in the same manner as in Example 1, and the extracted residue was reconsolidated with acetone to give crude 2,4-dimethylimidazole 1- 5-dithiocarboxylic acid-benzyl ester [M. p. l48-152
°C; TLC (same as Example 2) RfO. 48-0.58
;5.2y (yield 66% based on dithiocarboxylic acid)].

Example 21 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid 0.03 mol (5.58 da), benzyl chloride 0.
03 mol and 2 ml of DMF1 were reacted in the same manner as in the above example, and the crystals precipitated when cold were collected and washed with acetone to form crystals 7.7y, which were re-crystallized twice with ethanol. The crystal was made into a crystal of 5.3f.

The ammoniacal methanol solution of the crystals was then concentrated under reduced pressure, the residue was extracted with water in the same manner as in Example 1, and the extracted residue was reconsolidated with acetone to give 2-ethyl-4-methylimidazole-5-dithiocarphonic acid-benzyl ester. 1.
6f was obtained and used as an identification sample. Example 22 0.03 mol of 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid, 0.03 mol of benzyl chloride, 0.045 mol (1.8 f) of sodium hydroxide, and 12 m of water.
1 were reacted in the same manner as in the above example, the aqueous layer of the cold reaction mixture was decanted, the residue was extracted with acetone, the extract was dried under reduced pressure, and the dried product was reconsolidated with acetone to obtain a crude product. 2-Ethyl-4-methylimidazole-5-dithiocarboxylic acid-benzyl ester [M. p. 95-105°C: TLC (same as Example 2) RfO. 6O~0.70, 0.80~0
．． 82 (extremely thin); 3.29 (yield % relative to dithiocarboxylic acid)].

Example 23 0.03 mol (9.36y) of 2-undecyl-4-methylimidazole-5-dithiocarboxylic acid, 0.03 mol of benzyl chloride, and 2 ml of DMF1 were reacted in the same manner as in the previous example, and the system was concentrated under reduced pressure. A candy-like residue was obtained.

This product was dissolved in ethanol to make it ammoniacal, then concentrated under reduced pressure to dryness, the dried product was extracted with water in the same manner as in Example 1, and the toluene solution of the extraction residue was passed through a layer of activated clay. The first red solution was collected and concentrated under reduced pressure to obtain a viscous liquid. This liquid toluene solution was passed through the clay layer again and concentrated under reduced pressure to obtain a viscous residual liquid.
This was used as an identification sample of 2-undecyl-4-methylimidazole-5-dithiocarboxylic acid-benzyl ester.

Example 24 The reaction was carried out under the same conditions as in Example 23, the system was concentrated under reduced pressure, the residue was dissolved in ethanol to make it ammoniacal, the solution was concentrated under reduced pressure, and the resulting residue was used in Example 1.
Extract with 50ml of water in the same manner as above, pass the toluene solution of the extraction residue through activated clay, and collect the effluent. Concentrate under reduced pressure to obtain crude 2-undecyl-4-methylimidazole-5-dithiocarboxylic acid benzyl ester [red liquid; L°C (corresponding to Example 2) RfO. 7O~0.80; 5.09 (yield 4
1%)].

Example 25 0.03 mol of 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid, 0.03 mol of benzyl chloride
1.5 mol of magnesium carbonate and 20 ml of water were reacted in the same manner as in the previous example, the aqueous layer of the reaction mixture was decanted, the residue was extracted with acetone, the extract was dried, and the dried solid was reconsolidated with acetone. Crude 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid-benzyl ester [M. p.
lO2~108°C; L°C (same as Example 2) RfO. 4
6-0.50 (extremely thin); 4.5y (yield %)].

Example 26 0.03 mol of 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid, 0.03 mol of benzyl chloride, and 12 ml of dimethyl sulfoxide were reacted in the same manner as in the previous example, and crystals precipitated from the reaction mixture when cold. and washed with acetone to obtain crude 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid monobenzyl ester hydrochloride [
M. p. 2O2-210°C: 7TLC (same as Example 2) RfO. 5O~0.60 (extremely thin), 0.60
~0.70; 5.7f (yield 61%)] was obtained.

Example 272-Phenyl-4-methylimidazole-5
0.03 mol (7.02 f) of -dithiocarboxylic acid, 0.03 mol (7.02 f) of benzyl chloride, and 2 ml of DMF were reacted in the same manner as in the previous example, and the system was concentrated under reduced pressure to obtain a candy-like substance, which was dissolved in methanol. Dissolved to make it ammoniacal. The solution was concentrated under reduced pressure, and the resulting residue was extracted with water in the same manner as in Example 1. Acetone was added to the extracted residue and filtered to dryness. A methanol solution of the product was treated with activated carbon to make the solution sufficiently acidic with HCl, and then dried to obtain a dry product.

The dried product was recrystallized three times with ethanol and then twice with acetic acid to obtain 1 g of 2-phenyl-4-methylimidazole-5-dithiocarboxylic acid benzyl ester, which was used as an identification sample. Example 28 0.03 mol of 2-phenyl-4-methylimidazole-5-dithiocarboxylic acid, 0.03 mol of benzyl chloride, 0.015 mol (1.6 f) of sodium carbonate, and 20 wLL of acetonitrile were added in the same manner as in the previous example. 50Tn of the residue obtained by concentrating the reaction mixture under reduced pressure.
The extracted residue was made into a chloroform solution, passed through a layer of activated clay, the effluent was dried, the dried product was dissolved in methanol and made sufficiently acidic with HCl, and the solution After drying, reconsolidate with methanol to obtain crude 2-
Phenyl-4-methylimidazole-5-dithiocarboxylic acid monobenzyl ester hydrochloride [M. p. lOO~11
0°C: L°C (same as Example 2) RfO. 6O~0.6
6 (very thin), 0.66-0.76; 4.0y (yield 37%)].

Example 29 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid sodium salt 0.03 mol (5.6 g
), benzyl chloride 0.03 mol and ethanol 12 ml
The three components were reacted in the same manner as in the above example, and when cold, the reaction mixture was filtered, the solution was dried, and the dried product was reconsolidated with acetone to obtain crude 2-ethyl-4-methylimidazole-5-dithiocarbon. Acid-benzyl ester [M. P. 95-105℃
; Publication °C (same as Example 2) RfO. 44~0.47 (extremely thin) 0.52~0.63s0.78~0.80)
(very thin); 4.9y (yield 59%)].

Example 30 0.03 mol (4.7 f) of 4-methylimidazole-5-dithiocarboxylic acid, 0.03 mol (4.1 f) of sodium acetate trihydrate, 12 ml of acetic acid and 0.03 mol (3.8 f) of benzyl chloride. ) was maintained at a temperature of 75 to 80°C for 2 hours, then cooled and filtered, the resulting liquid was concentrated under reduced pressure, and the residue was boiled with 30 ml of water, cooled, and the aqueous layer was tilted. The residue was recrystallized with acetone to give crude 4-methyl-5-dithiocarboxylic acid.
Benzyl ester [M. p. l38-145℃: TLC
(Same as Example 2) RfO. 38～0.48〕4.4y
(yield 59%).

Example 31 2.4-dimethylimidazole-5-dithiocarboxylic acid 0.03 mol (5.2f), sodium carbonate 0.015
A system consisting of 20 ml of acetone and 0.03 mol of benzyl chloride (3.8 fI) was refluxed for 3 hours (1.6 fI).
After cooling (inner temperature: 60°C), the filtered solution was dried under reduced pressure, and the dried product was reconsolidated with acetone to obtain benzyl 2.4 dimethylimidazole-5-dithiocarboxylate [M. P. l33
~14rC; published °C (same as Example 2) RfO. 47-0
．． 58, 0.78-0.80 (very thin)] 6.0y (
A yield of 76% was obtained.

Claims (1)

[Claims] 1 Structural formula ▲ Numerical formulas, chemical formulas, tables, etc. The residue R_4 represents a hydrogen atom or a methyl group. It is characterized by causing a condensation reaction between the imidazoledithiocarboxylic acid shown in ] and a benzyl halide. Structural formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [However, in the formula, R_2 and R_4 are the same as above. ] A method for synthesizing benzyl imidazole dithiocarboxylic acid ester. 2. The method for synthesizing benzyl imidazole dithiocarboxylic acid ester according to claim 1, wherein imidazole dithiocarboxylic acid and benzyl halide are subjected to a condensation reaction and dehydrohalogenation is performed using a hydrogen halide acceptor. 3. The method for synthesizing benzyl imidazoledithiocarboxylic acid ester according to claim 1, wherein a salt of imidazoledithiocarboxylic acid is formed and a benzyl halide is subjected to a condensation reaction with the salt.