JPS6056713B2 - Synthesis method of imidazole dithiocarboxylic acid phenacyl ester compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for synthesizing an imidazole dithiocarboxylic acid phenacyl ester compound, and more specifically, a compound having the structural formula ゛'<0 [However, in the formula, R.

is a hydrogen atom or a residue R selected from the group consisting of a methyl group, an ethyl group, an undecyl group, a heptadecyl group, and a phenyl group. represents a hydrogen atom or a methyl group. [However, in the formula, R2 and R are the same as above.

] This relates to a method for synthesizing the imidazole dithiocarboxylic acid phenacyl ester compound. It is known that the imidazole dithiocarboxylic acid compound and its alkali metal salt, which are the starting materials of 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 imidazole dithiocarboxylic acid and phenacyl halide are subjected to a condensation reaction, the dithiocarboxylic acid phenacyl ester hydrogen halide salt is first produced according to the following reaction formula. ,
Then, the hydrogen halide salt is reacted with a hydrogen halide acceptor to obtain the target phenacyl ester. Further, when the starting material imidazoledithiocarboxylic acid and phenacyl halide are subjected to a condensation reaction in the presence of a hydrogen halide acceptor, the target phenacyl ester is obtained according to the reaction formula shown below. Further, when the starting material alkali metal salt of imidazole dithiocarboxylic acid and phenacyl halide are subjected to a condensation reaction, the target phenacyl ester can be similarly obtained according to the following reaction formula.

The starting alkali metal salts of imidazole dithiocarboxylic acids are primarily sodium and potassium salts.

When imidazole and carbon disulfide are reacted in the presence of an alkali hydroxide to synthesize imidazole dithiocarboxylic acid, the alkali metal salt of the dithiocarboxylic acid is first produced, so it can be directly used in the synthesis of imidazole dithiocarboxylic acid phenacyl ester. It can be used as a starting material. The dithiocarboxylic acid easily forms a salt with the basic ion B4, and as shown in the reaction formula below, the dithiocarboxylic acid B
Since it gives a salt, the B salt can also be used as a starting material.

The basic ions used as B4 are Ll8, Na
l, K1, Ca4l, Ba84, Mg8l, Znl4,
Cu44, Mnl4, CO4ll, Ni44, Fe44
4, Hg44, Snl4, Pbl4, NH4l, 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 more economical than the use of sodium and potassium salts. I don't think it's a good idea.

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, sNaOH, . KOH,. Ca(0H)2
Ba(0H)2, Mg(0H)2, Li2CO3, Na
2CO,. K2CO3, CacO2, BacO3, Mg
Tertiary amines such as CO3, CH3COONaCH3COOKl pyridine and Et3Ns, quaternary ammonium hydroxides (eg TritOnB9) and the like.

The phenacyl halides used in the present invention are phenacyl chloride, phenacyl bromide, and phenacyl iodide, but phenacyl aoidide is too expensive and judged to be less practical than the former two. .

Considering the reaction between active hydrogen in the solvent and phenacyl halide, theoretically it would be desirable for the solvent used in the reaction to have no active hydrogen, but experimental results show that such a prediction is not necessarily accurate. It has also 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, dimethyl formamide, dimethyl sulfoxide, acetonitrile, acetone, acetic acid, pyridine, etc.

The reaction of the present invention is exothermic. Therefore, in the case of large-scale synthesis, cooling is required at the start of the reaction, but in the case of small-scale synthesis, no special cooling is necessary. After the reaction has progressed to a certain extent, the heat generation weakens and heating becomes necessary. This is a method of temperature control when shortening the reaction time is taken into account. In this case, the reaction temperature may be maintained between room temperature and about 90°C. The reaction in this case is completed within about 5 hours.
A reaction temperature of 90'C or higher is not particularly required.

9 (generations) or less is sufficient.

In order to slow down the heat generation, it is desirable to gradually add phenacyl halide to the reaction system. It is of course possible to conduct 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 under normal pressure, there is no need to apply additional pressure.

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

However, it is uneconomical and unnecessary to use them in excessive quantities. It has no taste. Isolation and purification of the target product is carried out according to conventional methods.

Specific aspects thereof will be described later in Examples. Further, the implementation mode of this reaction will also be described later in Examples. Various imidazole dithiocarboxylic acid phenacyl ester compounds obtained by the method of the present invention are useful as 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 η°C (silica GNEtOH) is displayed. ]Imidazole-4-dithiocarboxylic acid Na salt R
f: 0.0 (derived from Na, B.T.B), 0.45 to 0
．． 60 (visual observation) 2-methylimidazole-4-dithiocarboxylic acid Na salt Rf: 0.0 (derived from Na, B.T.B.
), 0.50 to 0.60 (visual observation) 2-ethylimidazole-4-dithiocarboxylic acid Na salt Rf: 0.0 (derived from Na, B.T.B), 0.63 to 0.77 (visual observation) 2 −
Undecylimidazole-4-dithiocarboxylic acid Na salt Rf: 0.0 (derived from Na, B.T.B), 0.57~
0.70 (visual observation) 2-heptadecyl imidazole-4-dithiocarboxylic acid Na salt Rf: 0.0 (derived from Na, B
．． T. B), 0.63 to 0.75 (visual observation) 2-phenylimidazole-4-dithiocarboxylic acid Na salt Rf: 0.
0 (derived from Na, B.T.B), 0.52-0.66 (
Visual observation) 4-methylimidazole-5-dithiocarboxylic acid Na salt Rf: 0.0 (derived from Na, B.T.B), 0.
44-0.58 (visual observation) 2,4-dimethylimidazole-5-dithiocarboxylic acid Na salt Rf: 0.0 (derived from Na, B.T.B), 0.55-0.68 (visual observation) 2-ethyl 4-methylimidazole-5-dithiocarboxylic acid Na salt Rf: 0.0 (derived from Na, B.T.B), 0.
60-0.73 (visual observation) 2-phenyl-4-methylimidazole-5-dithiocarboxylic acid Na salt Rf: 0.0 (
Derived from Na, B. T. B), 0.62 to 0.74 (visual observation) Each of the above Na salts is 950 to 1030c1-1
shows strong νc=s absorption.

2 Imidazole dithiocarboxylic acid imidazo-4-dithiocarboxylic acid Reddish brown crystals.

neutral. M. p. l57-15 (1jC0 Slightly soluble in water, methanol, chloroform, acetone and acetic acid. DMF, .
Easily soluble in DMSO and NaOH aqueous solutions. TlC (Silica G
、． EtOHl (visual): RfO. 45-0.60. ν8
& Sn, 1438 (second absorption), 1025 (first absorption).

NMR (DMSO-D6) δ8.80, D,. lH:
7.7&DllHOMass: m/El44 (M, 1
11 (M+-SH) 68 (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. DMF1 Easily soluble in DMSO and NaOH aqueous solutions. TLC (supra): RfO. 5O~0.60. νU′
．． 1:1607 (third absorption), 1210 (first absorption),
1040 (second absorption). NMR (DMF-D7): δ7
．． 7.SllH; 2.67, S. ．． 3HOMass:m
/El58 (M+), 125 (M+1SH), 817e
IS44 (:C=S).

2-ethylimidazole-4-dithiocarboxylic acid reddish brown crystals. neutral. M. p. 137-139'CO Sparingly soluble in water, chloroform and acetic acid. Methanol, DMSO and Na
Easily soluble in OH aqueous solution.

TLC (supra): RfO. 64-0.77. νU′. 1
: 1605 (second absorption), 1045 (first absorption).

NMR (DMSO-D6) δ7.70, SllH; 2
．． 87, q1? ;1.24,T,. 3FIOMass:
m/El72 (M, 139 (M+-SH), 9 Mi9\
4 is also 2-undecylimidazole-4-dithiocarboxylic acid brown crystals.

neutral. M. p. ll6-119°C. Slightly soluble in water, chloroform and cold acetic acid. Soluble in methanol, acetone, and hot acetic acid. DMSO. ．． Easily soluble in DMF' and NaOH aqueous solutions. TW (supra): RfO. 7O~0.81. νU′. 1
:1602 (4th absorption), 1205 (3rd absorption), 10
42 (first absorption). NMR (CF2COOH) δ7
．． 98, SllH3. lO, T. ．． 2H; 1.88, M
．． ．． 2H; 1.30, Mll6H; 0.87, M. ．． 3
HOMaSS: m/E298 (M, 265 (M+-S
H), 233s22\44.

2-Heptadecyl imidazole-4-dithiocarboxylic acid brown crystals.

neutral. M. p. lO7-112°C. Slightly soluble in water, chloroform and cold acetic acid. Soluble in DMSO. TLC (mentioned above): R
fO. 63-0.750 νU'-1: 1600 (first absorption), 1525 (third absorption), 1040 (second absorption).
NMR (DMSO-D6) δ7.70, SllH;
2.80, M. ．． 2H; 1.65, M,. Sha 11.22
, Ml28H; 0.8 mm. ．． 3HOMass:m/E
M+ does not appear, 348 (M+-H2S), 33 tables 317
, 307, 30e) S4 is also 2-phenylimidazole-4-dithiocarboxylic acid brown crystals.

Mild acidity. M. P. l54~15rC0 water, methanol,
Slightly soluble in chloroform, acetic acid and acetone. Easily soluble in DMSO and NaOH aqueous solutions. L°C (mentioned above): RfO. 52～
0.660νU′. , :1618 (second absorption), 121
5 (third absorption), 1040 (first absorption).

NMR (DMSO-D6) δ&33~7.92, m
1? ;7.92,SllH;7.76~7.30sm,
．． 3H0MasS: m/E22O (M two, 187 (M+
-SH), . 14 tons 10 tons 77.

4-Methylimidazole-5-dithiocarboxylic acid reddish brown crystals.

neutral. M. p. 159-161°C. Slightly soluble in water, methanol, chloroform and acetic acid. Easily soluble in DMSO and NaOH aqueous solutions.

TLC (supra): RfO. 47-0.60. νUr. l
: 1590, 1440, 1375, 1265 (second absorption), 1120 (third absorption) 1020 (fourth absorption), 92
\860 ((first absorption), 800s720.

NMR (DMSO-D6) δ&60, SllH;2
．． 62, S. ．． 3HOMass:m/El58(M+)
, 125 (M+-SH), 81, 7 Mi 4402,4-dimethylimidazole-5-dithiocarboxylic acid red crystals.

M. p. 187-189'CO Sparingly soluble in water, methanol, ethanol, chloroform and acetone.

Soluble in acetic acid. Easily soluble in DMF' and DMSO. TLC (supra): RfO. 57 to 0.700 νu, 1615 (second absorption), 1025 and 990 (first absorption). NMR (
CF3COOH) δ2.77, S. ．． 3H2.7 to S. ．． 3HOMass: m/El72 (M two, 139 (
M+-SH), 95.4202-Ethyl-4-methylimidazole-5-dithiocarboxylic acid red-purple crystals.

neutral. M. p. l77-179'CO water, methanol,
Slightly soluble in ethanol and acetone. Soluble in acetic acid. Easily soluble in DMF and DMSO. TLC (supra): RfO. 6O~0
．． 700ν611: 1615 (second absorption), 1013 (
1st absorption).

NMR (DMSO-D6) δ2.80, Qs2H;
2.60ss. ．． 3H; 1.2λt1? HOMass:
m/El86 (M, 153 (M+-SH), 1 Otori 10
902-Phenyl-4-methylimidazole-5-dithiocarboxylic acid reddish brown crystals.

M. p. 165-168°C. Slightly soluble in water, methanol, ethanol, acetone, chloroform, t-butanol and benzene.

Soluble in acetic acid and methyl cellosolve. DMF,,DMSO
and soluble in NaOH aqueous solution.

L°C (mentioned above): RfO. 65~0.780νR. ll
625 (third absorption), 1603, 1540, 1485,
1215 (second absorption) 1040 (first absorption).

NMR (CF3COOH) δ8.00-7.50,
m1■; 2.8λS1 General Mass: m/E234 (M, 201 (M+-SH), 1 Seki, 10 Table 77.

3 Target Imidazole-4-dithiocarboxylic acid phenacyl ester Structural formula Physical properties Orange crystal.

neutral. M. p. 173-176°C (EtOH). acetic acid,
Soluble in DMSO and DMF. methanol, ethanol,
Slightly soluble in acetone and toluene. Insoluble in water. TLC (Silica G, CHCl3/MeOH=10/1v01. ratio,
12 colors): RfO. 3O~0.400ν torsion, 167
5 (first absorption), νc=0), 1057 (third absorption, ν
c=s).

NMR (DMSO-D6): δ8.14-7.40sm
1 station (phenyl proton); 7.99 S11H (2nd position proton); 7.8 飄SllHl (4th position proton); 5.
0 to S. ．． 2H (methylene proton of phenacyl group).

Mass: m/E262 (M, 229 (M+-S-H
), -157 (M+-Ph-CO), 143 (M+-P
hCOOH2), 111(M+-PhCOCH2S)1
05 (PhCO●) 77 (phenyl group), 44 (:C=
S). 2-Methylimidazole-4-dithiocarboxylic acid monophenacyl ester Structural formula Physical properties Yellow-orange crystals.

neutral. M. p. l7O~172℃. (EtOH). Soluble in acetic acid, DMSO and DMF'.

Slightly soluble in methanol, ethanol, acetone and toluene. Insoluble in water and chloroform. TLC (supra) RfO.
35~0.450νUr. l: 1679 (second absorption, ν
c=0), 1070 (third absorption, νc=S).

NMR (CF3COOH)゜δ&19~7.43, M,
．． 5H (phenyl group proton); &02, SllH (4
position proton); 5.11, S, . 2Hl (methylene proton of phenacyl group); 2.82, S. ．． 3H (methyl proton at 2nd position).

MaSS: m/E276 (M+), 243 (M+-S-
H), 171 (M+-PhCO), 157 (M+-Ph
COCH2), 125(M+-PhCOCH2S), 1
05 (PhCO●) 77 (phenyl group), 44 (:C=
S).

2-ethylimidazole-4-dithiocarboxylic acid phenacyl ester Structural formula Physical properties Yellow-orange crystals.

neutral. M. p. 157-159°C (EtOH). Methanol, ethanol, acetone, acetic acid, DMSO. ．． DM
Soluble in F' and toluene.

Insoluble in water. TLC (supra): RfO. 5O~0.600
νUr. l: 1676 (first absorption, νc=0), 104
8 (νc=S). NMR (CF3COOH) δ8.2
0-7.43, M. ．． 5l ((phenyl group proton):
8.0 Table SllH (4th position proton); 5.11, S, .
2H (methylene proton of phenacyl group); 3.15s
q. ．． 2H (methylene proton of 2-position ethyl group); 1.
50,. t. ．． 3H (methyl proton of 2-position ethyl group)
.

IS/1ass: m/E29O (M, 257 (M+-
S-H), 185 (M+-PhCO), 172 (M+-PhCOCH2+H), 139 (M+-PhCOCH2
S), 105 (PhCO●), 77 (phenyl group), 4
4 (:C=S).

2-Undecylimidazole-4-dithiocarboxylic acid phenacyl ester Structural formula Physical properties Yellow-orange crystals.

neutral. M. P. 135-13rC (acetone). Methanol, ethanol, acetone, acetic acid, DMSO1DMF
Soluble in toluene and chloroform.

Insoluble in water. TLC (supra): RfO. 7O~0.77.
ν6 anal,: 1683 (first absorption, νc=0), 1065
(νc=S).

NMR (CDCl2): δ8.13-7.40, M,.
5H (phenyl group proton); 7.78, MllH (4
position proton); 4.89, S, . 2H (methylene proton of phenacyl group); 2.72t, . 2H (α-methylene proton of undecyl group at 2-position); M. to 1.7. ．． 2H
(β-methylene proton of undecyl group at 2-position): 1.2
4, Mll6H (intermediate methylene proton of undecyl group at 2-position); 0.87, M,. 3H (terminal methyl proton of undecyl group at 2-position).

Mass: m/E4l6 (M, 384 (M+-S),
298-(M+-PhCOCH2+H), 297(M+
-PhCOCH2), 265(M+-PhCOCH2S
), 105 (PhCO●) 77 (phenyl group), 44 (
:C=S).

2-heptadecyl imidazole-4-dithiocal. Phenacyl ester structural formula Physical properties Yellow-orange crystal.

neutral. M. p. 125-12CfC (acetone). methanol, ethanol, acetone, acetic acid, chloroform,
DMSO1 Soluble in DMF and toluene.

Insoluble in water. TLC (supra): RfO. 7O~0.80.
νUr. l: 1678 (4th absorption, νc=0), 106
6 (νc=S). NMR (CDCl3): δ & 10~7
．． 43, M. ．． 5H (phenyl group proton); 7.77
, SllH (4-position proton); 4.88, SllH (4-position proton); ．． 2H(
methylene proton of phenacyl group); 2.71t. ．． 2
H (α-methylene proton of heptadecyl group at 2-position); 1
．． 75, Ml2H (β-methylene proton of heptadecyl group at 2-position); 1.24Nm128H (intermediate methylene proton of heptadecyl group at 2-position); 0.86, M. ．． 3H (
terminal methyl proton of the heptadecyl group at position 2).

Mass: M+ does not appear. 468 (M+-S), 3
49 (M+-PhCOCH2S), 317 (M+-Ph
COCH3S-S), 105 (PhCO.), 77 (phenyl group), 44 (:C=S).

Sea-phenylimidazole - 4-dithiocarbonic phenacyl ester ξ-formulated orange crystal.

neutral. M. P. 17O-177C (EtOH). Soluble in toluene, acetic acid, DMSO and DMF. Slightly soluble in methanol, ethanol and acetone. Insoluble in water. TLC (supra): RfO. 62~0.720νU'. 1:1680 (
1st absorption, νc=0), 1073 (3rd absorption, νc=S
). NMR (DMSO-D6) δ8.20-7.3
7m110H (2 protons of phenyl group): &13s
s,. 1H (proton at 4th position): 5.03, S,. 2H (
methylene proton of phenacyl group).

Mass: 338 (M, 306 (M+-S) 305 (
M+-S-H), 233(M+-PhCO), 220(
M+-PhCOCH2+H), 219(M+-PhCO
CH2), 187 (M+-PhCOCH2S), 105
(PhCOOl77 (phenyl group), 44 (:C=S)
.

;-Methylimidazole-5-dithiocarboxylic acid phenacyl ester structural formula Physical properties Orange crystals.

neutral. M. p. 169-171°C (EtOH). acetic acid,
Soluble in DMSO and DMF. methanol, ethanol,
Slightly soluble in acetone and toluene. Insoluble in water and chloroform. TLC (supra): RfO. 35~0.450νUr
．． l: 1681 (second absorption, νc=0), 1052 (first absorption, νc=S).

NMR (CF3COOH): δ8.66, SllH (2
position proton); 8.22-7.47), m1, 5H (phenyl group proton); 5.18, S, . 2H (methylene proton of phenacyl group); 2.96, S. ．． 3H (4
methyl proton).

Mass: 276 (M, 243 (M+-S-H), 1
71 (M+-PhCO), 157 (M+-PhCOCH
2), 125(M+-PhCOCl(2S), 105(
PhCOOl77 (phenyl group), 44 (:C=S).

2,4-dimethylimidazole-5-dithiocarboxylic acid phenacyl ester Structural formula Physical properties Yellow-orange crystals.

neutral. M. P. 175-17rc (EtOH). acetic acid,
Soluble in DMSO and DMF.

Slightly soluble in methanol, ethanol, acetone and toluene. Insoluble in water. TLC (supra): RfO. 35-0.45
0v8! '． 11680 (first absorption, νc=0), 10
60 (νc=S).

NMR (CF3COOH): δ&20~7.45, M,
．． 5H (phenyl group proton); M Sl2H (methylene proton of phenacyl group); 2.87, Sl3H (2
position methyl proton): 2.75, S, . 3H (4-position methyl proton).

Mass: 290 (M, 257 (M+-S-H), 1
85 (M+-PhCO), 171 (M+PhCOCH2
), 139 (M4-PhCOCH2S), 105 (Ph
CO●) 77 (phenyl group), 44 (:C=S).

2-Ethyl-4-methylimidazole-5-dithiocarboxylic acid phenacyl ester Structural formula Physical properties Yellow crystals.

neutral. M. p. 176-178°C (EtOH). acetic acid,
Soluble in DMSO and DMF'. Slightly soluble in methanol, ethanol, acetone and toluene. Insoluble in water and chloroform. TLC (supra): RfO. 5O~0.60uPW
r. l: 1670 (second absorption, νc = 0), 1038 (
νc=S).

NMR (CF3COOH): δ8.23-7.47, m
1 station (phenyl group proton); 5.15ss, b2H (
Methylene proton of phenacyl group): 3.10, Ql2
H (methylene proton of 2-position ethyl group) 2.8 gss,
．． 3H (4-position methyl proton); 1.48, T. s3H
(Methyl proton of 2-position ethyl group).

Mass; 304 (M+), 271 (M+-S-H),
199 (MiPhCO), 185 (MiPhCOCH2
), 153 (M+-PhCOCH2S), 105 (Ph
CO●) 77 (phenyl group), 44 (:C=S). 2-
Phenyl-4-methylimidazole-5-dithiocarboxylic acid phenacyl ester Structural formula Physical properties Yellow-orange crystals.

neutral. M. p. 194-197°C (EtOH). acetic acid,
Soluble in DMSO and DMF'.

Slightly soluble in methanol, EtOH, acetone and toluene.
Insoluble in water. TLC (supra): RfO. 6O~0.70.

νUr. l: 1666 (third absorption, νc=0), 104
7 (fourth absorption, νc=S). NMR (DMSO-D6)
: δ8.17-7.37, MllOH (2 protons of phenyl group); 4.92, S. ．． 2H (methylene proton of phenacyl group); 2. Kana, S,,3H (4-position methyl proton). r! 4ass: m/E352 (M, 31
9 (M+-S-H), 247 (M+-PhCO), 23
3 (M÷-PhCOCH2), 201 (M+-PhCO
CH2S), 105 (PhCO●), 77 (phenyl group), 44 (:C=S).

Example 1 A reaction vessel equipped with a reflux condenser was mounted on a magnetic stirring hot plate, and 0.02 mol (2.9y) of imidazole-4-dithiocarboxylic acid and 0.01 mol (0.7 y) of calcium hydroxide were added.
') and 20 ml of methanol were added, then 0.02 mol (4.0 y) of phenacyl bromide was added all at once at room temperature while stirring, and the system was heated under reflux for 2 hours (inner temperature 6 rC), and the precipitated crystals were collected at the door. The crystals were recrystallized with ethanol to obtain the crude target product [M. p. 173-176℃; TLC (silica G1 chloroform/methanol 10/1 volume ratio, 1
2 colors) RfO. 3O~0.40] was obtained in an amount of 4.0f (yield relative to dithiocarboxylic acid: 76%).

Example 2 The heated ethanol solution of the crude target product of Example 1 was treated with activated carbon, and the crystals precipitated when cold were collected from the furnace liquid obtained. I got it.

Example 3 2-methylimidazole-4-dithiocarboxylic acid 0.0
2 mol (3.2y), potassium carbonate 0.01 mol (1.
A system consisting of 4y) and 20 ml of water was heated to 50 to 6 (range), and while maintaining the same temperature, 0.02 mol (4.0 Da) of phenacyl bromide was added little by little over 1 hour. After keeping the temperature at 50 to 60°C for an additional hour, the crystals were taken off the coast, and the crystals were reconsolidated with ethanol to obtain the crude target product [M. p. l
7O-177C; TLC (corresponding to Example 1) RfO. 35
~0.45] to 4.6f (yield of dithiocarboxylic acid %
) got it.

Example 4 The crude target product of Example 3 was treated as in Example 2 to obtain the identified sample (M.p.17O-177C).

Example 5 2-methylimidazole-4-dithiocarboxylic acid 0.02 mol (3.2y), magnesium carbonate 1.
A system consisting of 0y1 and 20ml of water is heated to 50-60°C, and while maintaining the same temperature, 0.0ml of phenacylbromide is added.
Add 2 mol (4.0 f1) little by little over 1 hour,
After keeping the temperature at 50-60'C for an additional hour, the crystals were taken off the coast, and the crystals were recrystallized with ethanol to obtain the crude target product [M. p. l
69-177C; Published ℃ (supra) RfO. 35-0.45
] was obtained (yield 85% based on dithiocarboxylic acid).
Example 6 2-methylimidazole-4-dithiocarboxylic acid 0.
02 mol (3.2y), potassium hydroxide 0.02 mol (
1.1y), DMSO2Oml, and phenacyl chloride 0.02mol (3.1y) were kept at 50~6(s) for 2 hours, then the crystals were taken out and poured into 30ml of cold water. Wash with coarse target material [M. p. l68~1
71°C; 2.5 fI (yield 45% based on dithiocarboxylic acid) was obtained.

Example 7 2-ethylimidazole-4-dithiocarboxylic acid 0.0
A system consisting of 2 mol (3.4 y), 20 ml of pyridine, and 0.02 mol (4.0 f) of phenacyl bromide was maintained at 50 to 60'C for 2 hours, and the contents were dried under reduced pressure. The dried product was washed with 30 Tnt of hot water and then cooled.
Crystals? The crystals were re-condensed with ethanol to obtain the crude target product [
M. p. l49-152°C; TLC (supra) RfO. 5
O ~ 0.60] to 3.5f (yield of dithiocarboxylic acid 6
0%) got it.

Example 8 A hot ethanol solution of the crude target product of Example 7 was treated with activated carbon, and the crystals precipitated when cold were collected from the Oki liquid. M.p.l5
7 to 15 (ages)).

Example 9 0.015 mol (4.5 f) of 2-undecylimidazole-4-dithiocarboxylic acid, 0.015 mol of sodium hydroxide. (stomach). 6y), ethanol 20ml
and phenacylbromide 0.015 mol (3.0y)
After keeping the system consisting of the four components at 50 to 60°C for 2 hours, the crystals were collected, washed with 30 TfL1 of cold water, and then reconsolidated with acetone to obtain the crude target product [M. p. l3O~134℃
; TLC (supra) RfO. 7O~0.77] to 4.4y
(70% yield relative to dithiocarboxylic acid).

Example 10 What are the crystals that precipitate when cold from the solution obtained by treating the hot acetone solution of the crude target product of Example 9 with activated carbon? The Okikiri crystals were reconsolidated with acetone, and the identified sample (M.p.l35~
13rC) was obtained.

Example 11 2-heptadecyl imidazole-4-dithiocarboxylic acid 0.01 mol (3.8y), sodium hydroxide 0.01
Mol (4). 4f), a system consisting of 25 ml of ethanol and 0.01 mol (1.6 g) of phenacyl chloride was kept at 50 to 60°C for 2 hours, and then the crystals were taken out of the oven, and the crystals were washed with 30 ml of cold water. Acetone was reconstituted to give the crude target product [M. p. l22-128℃ TLC (mentioned above) Rf
O. 7O~0.80] was obtained (3.4y (% yield relative to dithiocarboxylic acid)).

Example 12 The crude target product of Example 11 was treated as in Example 10 to obtain the identified sample (M.p.l 25-129'C).

Example 13 2-phenylimidazole-4-dithiocarboxylic acid 0.02 mol (4.4 V), triethylamine 0
．． A system consisting of 02 mol (20 y), 20 ml of ethanol, and 0.02 mol (4.0 y) of phenacyl bromide was kept at 50-60'C for 2 hours, and then the crystals were taken out and poured into 30 ml of cold water. Rinse and remove coarse object [M. p.
17O~172°C: TLC (supra) RfO. 62-0.
72] was obtained in an amount of 5.5 f (yield based on dithiocarboxylic acid: 81%).

Example 14 The crude target product of Example 13 was treated as in Example 8 to obtain the identified sample (M.p.17O-177C).

Example 15 2-phenylimidazole-4-dithiocarboxylic acid 0.02 mol (4.4y), sodium acetate 0.
After keeping the system consisting of 02 mol (1.6 f), acetic acid 20 ml, and phenacyl bromide 0.02 mol (4.0 After washing with ethanol and reconsolidating with ethanol, the crude target product [M. p. l67-171-C; TLC (mentioned above) Rf
O. 62-0.72] (yield 47% based on dithiocarboxylic acid). Example 16 4-methylimidazole-5-dithiocarboxylic acid 0.02 mol (3.2y), 2
8% ammonia water 0.02 mol (1.2y), water 20m
L and phenacylbromide 0.02 mol (4.0y)
After keeping the system consisting of the four members at 50-60℃ for 2 hours, the crystals are formed. The crystals were collected and recrystallized with ethanol to obtain the crude target product [M.
p. l67-170°C; TLC (supra) RfO. 35～
0.45] to 4.0y (yield 72% based on dithiocarboxylic acid)
) got it.

Example 17 The crude target product of Example 16 was treated as in Example 8 to obtain the identified sample (M.P.l 69-17rC).

Example 18 0.02 mol (3.4 g) of 2,4-dimethylimidazole-5-dithiocarboxylic acid, 0.01 mol (1.1 f1) of sodium carbonate, 20 mt of acetone and 0.02 mol (4.0 y) of phenacyl bromide. After the system consisting of the four components was heated under reflux for 5 hours (inner temperature 5rC), the crystals were collected, washed with 30 mL of cold water, and then reconsolidated with ethanol to obtain the crude target product [M. p. l75~17℃; TL
C (supra) RfO. 35-0.45] was obtained in an amount of 4.4y (yield 75% based on the dithiocarboxylic acid).

- Example 19 The crude target product of Example 18 was treated as in Example 2 to obtain the identified sample (M.P. 175-17rc).

Example 202-Ethyl-4-methylimidazole-5-
A system consisting of 0.02 mol (3.711) of di-thiocarboxylic acid, 15 ml of dimethylformamide and 0.02 mol (4.0 f) of phenacyl bromide was heated for 2 hours.
After keeping the content at 0 to 60°C, the contents were dried under reduced pressure, and the dried product was reconsolidated with ethanol to obtain crystalline ammoniacal meth)
The nol solution was dried under reduced pressure, and the dried product was washed with 30 ml of water and then reconsolidated with ethanol to obtain the crude target product [M. p. l76~
178°C; TLC (supra) RfO. 5O~0.60] (yield 74% based on dithiocarboxylic acid).

Example 21 The crude target product of Example 20 was reconsolidated with ethanol to obtain an identified sample (
M. p. 176-178°C).

Example N2-Ethyl-4-methylimidazole-5-dithiocarboxylic acid 0.02 mol (3.7 f), calcium carbonate 0.01 mol (1.0'), dimethylformamide 20 ml and phenacyl bromide 0.02 mol (4
．． The system consisting of the four components of 0f) was maintained at 80 to 9 CfC for 5 hours and then filtered, the lach was concentrated under reduced pressure, and the residue was reconsolidated with ethanol to obtain the crude target product [M. p. l6O~163℃;T
lC (supra) RfO. 5O~0.60] was obtained (yield 26% based on dithiocarboxylic acid).

Example 23 A system consisting of 0.02 mol (4.2 fI) of 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid sodium salt, 20 ml of ethanol, and 0.02 mol (3.1 f) of phenacyl chloride was heated for 1 hour. After keeping the temperature at 50 to 60°C, the crystals were collected, washed with 30 ml of cold water, and then reconsolidated with ethanol to obtain the crude target product [M. p. l73
~176°C; T(1) (supra) RfO. 5O~0.60
] was obtained by 5.1y (yield % of sodium dithiocarboxylic acid salt).

Example 24 2-phenyl-4-methylimidazole-5-dithiocarboxylic acid 0.02 mol (4.7y), sodium carbonate 0
．． After maintaining the system consisting of 01 mol (1.1 f), 20 ml of acetonitrile, and 0.02 mol (4.0 f) of phenacyl bromide at a temperature of 50 to 6 (generations) for 2 hours, the crystals were collected. was washed with 30 ml of cold water and then reconsolidated with ethanol to obtain the crude target material [M. P. 194-19rc: Published ℃
(Supra) RfO. 6O to 0.71 was obtained by 4.1f (% yield relative to dithiocarboxylic acid).

Example 25 The crude target product of Example 24 was treated as in Example 2 to obtain the identified sample (M.P. 194-19rc).

Claims (1)

[Claims] 1 Structural formula ▲ Numerical formulas, chemical formulas, tables, etc. The residue R_4 represents a hydrogen atom or a methyl group. ] A structural formula characterized by the condensation reaction of an imidazole dithiocarboxylic acid compound and phenacyl halide ▲ There are numerical formulas, chemical formulas, tables, etc. ▼ [However, in the formula, R_2 and R_4 are the same as above. ] A method for synthesizing an imidazole dithiocarboxylic acid phenacyl ester compound. 2 Condensation reaction of imidazole dithiocarboxylic acid compound and phenacyl halide,
A method for synthesizing an imidazole dithiocarboxylic acid phenacyl ester compound according to claim 1, wherein the compound is dehydrohalogenated using a hydrogen halide acceptor. 3. The method for synthesizing an imidazoledithiocarboxylic acid phenacyl ester compound according to claim 1, wherein the imidazoledithiocarboxylic acid compound and phenacyl halide are subjected to a condensation reaction in the presence of a hydrogen halide acceptor. 4. The method for synthesizing an imidazoledithiocarboxylic acid phenacyl ester compound according to claim 1, which comprises forming a salt of an imidazoledithiocarboxylic acid compound and subjecting the salt to a condensation reaction with phenacyl halide.