JPS6141912B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for synthesizing an imidazole dithiocarboxylic acid cyanoethyl ester compound, and specifically relates to a method for synthesizing an imidazole dithiocarboxylic acid cyanoethyl ester compound, and specifically,

[Formula] [In the formula, R ₂ represents 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, and R ₄ represents a hydrogen atom or a methyl group. ] A structural formula characterized by an addition reaction between an imidazole dithiocarboxylic acid compound and acrylonitrile represented by [However, in the formula, R ₂ and R ₄ are the same as above. ] This relates to a method for synthesizing the imidazole dithiocarboxylic acid cyanoethyl ester compound shown below. The imidazole dithiocarboxylic acid compound, which is the starting material 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 JP-A-57-176965. When the starting material imidazoledithiocarboxylic acid and acrylonitrile are subjected to an addition reaction, the desired product cyanoethyl ester is obtained according to the reaction formula shown below. Since the reaction of the present invention proceeds without a solvent, there is no need to use a separate solvent, but if control of the reaction temperature is taken into consideration, an aprotic solvent such as dimethylformamide can also be used. The reaction of the present invention is exothermic. Therefore, in the case of large-scale synthesis, cooling is required at the beginning of the reaction, but
In the case of small-scale reactions, there is no need for additional cooling. After the reaction has progressed to a certain extent, the heat generation weakens, so heating is necessary. 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 about 80°C. The reaction in this case is completed within about 5 hours.
A reaction temperature of 80°C or higher is not particularly required. A temperature below 80℃ is sufficient. To slow down fever,
It is desirable to gradually add acrylonitrile to 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 consideration. 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 between imidazoledithiocarboxylic acid and acrylonitrile, 1 molar equivalent or more than 1 molar equivalent of acrylonitrile may be used per 1 molar equivalent of the starting material dithiocarboxylic acid. However, it is uneconomical and meaningless to use them in excessive quantities. 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 cyanoethyl ester compounds obtained by the method of the present invention are useful as agricultural chemical intermediates and pharmaceutical intermediates. Next, the properties of the target product synthesized by the method of the present invention will be illustrated. Imidazole-4-dithiocarboxylic acid cyanoethyl ester structural formula Physical propertiesOrange crystal. neutral. mp164-166℃ (acetone). Methanol, ethanol, acetone, acetic acid and
Soluble in DMSO. Poorly soluble in water. TLC (Silica G,
_CHCl3 /MeOH=10/1vol. ratio, _I2 color development):
Rf0.30~0.40. ν ^KBr cm ₋₁ : 2240 (νc≡N), 1067 (νc=S)
. NMR (CF ₃ COOH); δ8.86, d 1H (proton at 2nd position); 8.15, d, 1H (proton at 4th position); 3.85, t, 2H (α- of cyanoethyl group)
methylene proton); 3.03, t, 2H (β-methylene proton of cyanoethyl group). Mass: m/e197 (M ⁺ ), 144 (M ⁺ -
CH ₂ CH ₂ CN + H), 111 (M ⁺ -SCH ₂ CH ₂ CN). 2-Methylimidazole-4-dithiocarboxylic acid cyanoethyl ester structural formula Physical propertiesOrange crystal. neutral. mp140-142℃ (EtOH). Soluble in methanol, ethanol, acetone and acetic acid. Poorly soluble in water. TLC (mentioned above): Rf0.35~
0.40. ν ^KBr cm ₋₁ : 2250 (νc≡N), 1075 (first absorption,
νc=S). NMR (CF ₃ COOH): δ7.97, S, 1H (4-position proton); 3.81, t, 2H (α-methylene proton of cyanoethyl group); 3.01, t, 2H
(β-methylene proton of cyanoethyl group);
2.82, s, 3H (methyl proton at 2nd position). Mass: m/e211 (M ⁺ ), 158 (M ⁺ -
CH ₂ CH ₂ CN + H), 125 (M ⁺ -SCH ₂ CH ₂ CN). 2-ethylimidazole-4-dithiocarboxylic acid cyanoethyl ester structural formula Physical propertiesOrange crystal. neutral. mp70~102℃ (acetone). Methanol, ethanol, acetone, acetic acid, chloroform, acetonitrile, DMSO,
Soluble in DMF, hot toluene and hot water. Slightly soluble in cold toluene and cold water. TLC (mentioned above):
Rf0.46~0.56. ν ^KBr cm ₋₁ : 2255 (νc≡N), 1045 (first absorption,
νc=s). NMR (CF ₃ COOH): δ7.99,
s, 1H (4-position proton); 3.81t, 2H (α-methylene proton of cyanoethyl group); 3.15,
q, 2H (methylene proton of 2-position ethyl group); 3.00, t, 2H (β- of cyanoethyl group)
methylene proton); 1.50, t, 3H (methylene proton of the 2-position ethyl group). Mass: m/e225
(M ⁺ ), 172 (M ⁺ - CH ₂ CH ₂ CN + H), 139 (M ⁺
-SCH ₂ CH ₂ CN). 2-Undecylimidazole-4-dithiocarboxylic acid cyanoethyl ester structural formula Physical properties Yellow-orange crystal. neutral. mp92~95℃ (acetone). Soluble in methanol, ethanol, acetone, acetic acid, chloroform, toluene, DMSO and DMF. Insoluble in water. TLC (mentioned above): Rf0.65~0.75. ν ^KBr cm ₋₁ : 2255 (νc≡N), 1060 (second absorption,
νc=S). NMR (CF ₃ COOH): δ8.00,
S, 1H (4-position proton); 3.82, t, 2H (α-methylene proton of cyanoethyl group);
3.13, t, 2H (α-methylene proton of undecyl group at 2-position); 3.01, t, 2H (β-methylene proton of cyanoethyl group); 1.90, m,
2H (β-methylene proton of undecyl group at 2-position); 1.33, m, 16H (intermediate methylene proton of undecyl group at 2-position); 0.89, m, 3H (terminal methyl proton of undecyl group at 2-position). Mass: m/e351 (M ⁺ ), 298 (M ⁺ -
CH ₂ CH ₂ CN + H), 297 (M ⁺ - CH ₂ CH ₂ CN),
265 (M ⁺ _—SOH2CH2CN ) _. 2-heptadecyl imidazole-4-dithiocarboxylic acid cyanoethyl ester structural formula Physical properties Yellow-orange crystal. neutral. mp101~104℃. Soluble in methanol, ethanol, acetone, acetic acid, chloroform, toluene and DMSO. Insoluble in water. TLC (mentioned above): Rf0.67~0.77. ν ^KBr cm ₋₁ : 2255 (νc≡N), 1066 (νc=S)
.
NMR (CF ₃ COOH): δ8.01, S, 1H (4-position proton); 3.82, t, 2H (α-methylene proton of cyanoethyl group); 3.14, t, 2H
(α-methylene proton of heptadecyl group at 2-position); 3.01, t, 2H (β- of cyanoethyl group)
methylene proton); 1.93m, 2H (β-methylene proton of heptadecyl group at 2-position); 1.33,
m, 28H (intermediate methylene proton of heptadecyl group at 2-position); 0.89, m, 3H (terminal methyl proton of heptadecyl group at 2-position). Mass: m/e435 (M ⁺ ), 381 (M ⁺ -
CH ₂ CH ₂ CN), 349 (M ⁺ -SCH ₂ CH ₂ CN). 2-phenylimidazole-4-dithiocarboxylic acid cyanoethyl ester structural formula Physical propertiesOrange crystal. neutral. mp119-121℃. Soluble in methanol, ethanol, acetone, acetic acid, chloroform, toluene, DMSO and DMF. Poorly soluble in water. TLC (mentioned above): Rf0.56~0.66. ν ^KBr cm ₋₁ ; 2250 (νc≡N), 1066 (first absorption,
νc=S). NMR (CF ₃ COOH): δ8.16,
S, 1H (4th position proton); 8.03-7.63, m,
5H (2nd position phenyl proton); 3.84, t, 2H
(α-methylene proton of cyanoethyl group);
3.03, t, 2H (β-methylene proton of cyanoethyl group). Mass: m/e273 (M ⁺ ), 220 (M ⁺ -
CH ₂ CH ₂ CN + H), 187 (M ⁺ -SCH ₂ CH ₂ CN),
104 (Ph-C=NH), 77 (Ph・). 4-Methylimidazole-5-dithiocarboxylic acid cyanoethyl ester structural formula Physical propertiesOrange crystal. neutral. mp145-147℃ (acetone). methanol, ethanol, acetone, acetic acid,
Soluble in DMSO, DMF, hot toluene and hot water.
Slightly soluble in cold toluene and cold water. TLC (mentioned above): Rf0.30~0.40. ν ^KBr cm ₋₁ : 2255 (νc≡N), 1052 (first absorption,
νc=S). NMR (CF ₃ COOH): δ8.66,
S, 1H (2-position proton); 3.86, t, 2H (α-methylene proton of cyanoethyl group);
3.05, t, 2H (β-methylene proton of cyanoethyl group); 2.90, S, 3H (methyl proton at 4-position). Mass: m/e211 (M ⁺ ), 158 (M ⁺ -
CH ₂ CH ₂ CN + H), 125 (M ⁺ -SCH ₂ CH ₂ CN). 2,4-dimethylimidazole-5-dithiocarboxylic acid cyanoethyl ester structural formula Physical propertiesOrange crystal. neutral. mp156-158℃ (acetone). Soluble in methanol, ethanol, acetone, acetic acid, chloroform, DMSO, DMF, hot toluene and hot water. Slightly soluble in cold toluene and cold water.
TLC (mentioned above): Rf0.38~0.48. ν ^KBr cm ₋₁ : 2255 (νc≡N), 1062 (second absorption,
νc=S). NMR (CF ₃ COOH): δ3.84,
t, 2H (α-methylene proton of cyanoethyl group); 3.03, t, 2H (β-methylene proton of cyanoethyl group);
-methylene proton); 2.83, S, 3H (methyl proton at 2nd position); 2.75, S, 3H (methyl proton at 4th position). Mass: m/e225 (M ⁺ ), 172 (M ⁺ -
CH ₂ CH ₂ CN + H), 139 (M ⁺ - CH ₂ CH ₂ CN +
H) 139 (M ⁺ - SCH ₂ CH ₂ CN). 2-Ethyl-4-methylimidazole-5-dithiocarboxylic acid cyanoethyl ester structural formula Physical propertiesOrange crystal. Neutral, mp163-165℃ (EtOH). Soluble in methanol, ethanol, acetone, acetic acid, chloroform, benzene, DMSO and DMF. Poorly soluble in water. TLC (mentioned above): Rf0.45~0.55. ν ^KBr cm ₋₁ : 2255 (νc≡N), 1045 (second absorption,
νc=S). NMR (CDCl ₃ ): δ3.58, t, 2H (α-methylene proton of cyanoethyl group); 2.80, t,
2H (α-methylene proton of cyanoethyl group); 2.80, t, 2H (β-methylene proton of cyanoethyl group)
methylene proton); 2.71, q, 2H (methylene proton at 2-position ethyl group); 2.60, S, 3H
(4-position methyl proton); 1.30, t, 3H (2-position ethyl group methyl proton). Mass: m/e239 (M ⁺ ), 186 (M ⁺ -
CH ₂ CH ₂ CN + H), 153 (M ⁺ -SCH ₂ CH ₂ CN). 2-phenyl-4-methylimidazole-5-dithiocarboxylic acid cyanoethyl ester structural formula Physical propertiesOrange crystal. neutral. mp153-156℃ (EtOH). Soluble in methanol, ethanol, acetone, acetic acid, chloroform, toluene, DMSO and DMF. Poorly soluble in water. TLC (mentioned above): Rf0.60~0.70. ν ^KBr cm ₋₁ : 2250 (νc≡N), 1054 (fourth absorption,
νc=S). NMR (CF ₃ COOH): δ8.01~7.63, m, 5H
(2-position phenyl proton); 3.89, t, 2H (α-methylene proton of cyanoethyl group);
3.07, t, 2H (β-methylene proton of cyanoethyl group); 2.93, S, 3H (methyl proton at 4-position). Mass: m/e287 (M ⁺ ), 234 (M ⁺ -
CH ₂ CH ₂ CN + H), 201 (M ⁺ -SCH ₂ CH ₂ CN),
104 (Ph-C=NH), 77 (Ph・) Example 1 A reaction vessel equipped with a reflux condenser was placed on a magnetic stirring hot plate, and 0.03 mol (4.3 g) of imidazole-4-dithiocarboxylic acid, Prepare 15 ml of DMF and 0.06 mol (3.2 g) of acrylonitrile for 3 hours.
After keeping the temperature at 70-80℃, the contents were concentrated under reduced pressure, the residue was extracted with 60 ml of hot acetone, the extract was treated with activated carbon, the resulting liquid was concentrated under reduced pressure, and the acetone solution of the residue was poured into an activated clay layer. The passing liquid is dried and solidified.
The dried product was reconsolidated with acetone to obtain the crude target product [mp150~
160℃; TLC (Silica G, chloroform/methanol = 10/1 volume ratio, _I2 color development) Rf0.30-0.40,
0.64-0.74 (extremely thin)] (yield 13.5% based on dithiocarboxylic acid) was obtained. Example 2 The hot acetone solution of the crude target product in Example 1 was treated with activated carbon, and the crystals precipitated when cold were collected. ℃) was obtained. Example 3 A system consisting of 0.03 mol (4.7 g) of 2-methylimidazole-4-dithiocarboxylic acid, 20 ml of DMF, and 0.03 mol (1.6 g) of acrylonitrile was kept at 70 to 80°C for 2 hours, and then the contents were depressurized. Concentrate, extract the residue with 100 ml of hot acetone, treat the extract with activated carbon, concentrate the resulting solution under reduced pressure, pass the acetone solution of the residue through a layer of activated clay, dry the filtered liquid, and dry. The solid was reconsolidated with ethanol to obtain the crude target product [mp125-136℃; TLC (mentioned above) Rf0.35-0.45,
0.68-0.72 (extremely thin)] (yield 12.6% based on dithiocarboxylic acid) was obtained. Example 4 The hot ethanol solution of the crude target product of Example 3 was treated with activated carbon, and the crystals that precipitated when cold were collected from the solution, and the collected crystals were reconsolidated twice with ethanol.
The previously identified sample (mp 140-142°C) was obtained. Example 5 A system consisting of 0.03 mol (5.2 g) of 2-ethylimidazole-4-dithiocarboxylic acid and 0.03 mol (1.6 g) of acrylonitrile was heated at 70 to 80°C for 1 hour.
After maintaining the temperature, the contents were concentrated under reduced pressure to reduce the residue to 100
ml of hot acetone, the extract was treated with activated carbon, the resulting liquid was concentrated under reduced pressure, the acetone solution of the residue was passed through a layer of activated clay, the passed liquid was dried, and the dried solid was reconsolidated with ethanol. and coarse object [mp70~102
2.5 g (yield based on dithiocarboxylic acid: 37.0%) was obtained. Example 6 The crude target product of Example 5 was re-crystallized twice with ethanol and then twice with acetone to obtain the above-mentioned identified sample (mp 70-102°C). Example 7 0.015 mol (4.5 g) of 2-undecylimidazole-4-dithiocarboxylic acid and acrylonitrile
A system consisting of 0.03 mol (1.6 g) of two components was heated for 2 hours70
After keeping the temperature at ~80°C, the contents were concentrated under reduced pressure, the acetone solution of the residue was passed through a layer of activated clay, the passed liquid was treated with activated carbon, the resulting liquid was dried, and the dried substance was reconsolidated with acetone. , crude target [mp82~91℃; TLC
2.8 g (yield based on dithiocarboxylic acid: 53.2%) of Rf0.65-0.75] was obtained. Example 8 The crude target product of Example 7 was treated as in Example 2 to obtain the identified sample (mp 92-95°C). Example 9 A system consisting of 0.01 mol (3.8 g) of 2-heptadecyl imidazole-4-dithiocarboxylic acid and 0.04 mol (2.1 g) of acrylonitrile was heated for 2 hours.
After keeping the temperature at 70-80°C, the contents were concentrated under reduced pressure, the hot acetone solution of the residue was treated with activated carbon, the resulting liquid was dried, and the dried product was reconsolidated with ethanol to obtain the crude target product [mp80-95 2.9 g (66.6% yield based on dithiocarboxylic acid) of Rf0.56-0.63 (thin), 0.67-0.77] was obtained. Example 10 The hot ethanol solution of the crude target product of Example 9 was treated with activated carbon, the resulting liquid was dried, the dried product was reconsolidated with ethanol, and then reconsolidated twice with acetone, resulting in crystals. Pass the acetone solution through the activated clay layer,
The passed liquid was dried and the identified sample (mp101~
104℃). Example 11 0.03 mol (6.6 g) of 2-phenylimidazole-4-dithiocarboxylic acid and 0.06 acrylonitrile
mol (3.2 g) of the system consisting of the two components for 2 hours at 70-80
After keeping at ℃, the contents were concentrated under reduced pressure, the hot acetone solution of the residue was treated with activated carbon, the resulting liquid was passed through a layer of activated clay, the passed liquid was dried, and the dried substance was reconsolidated with ethanol. Crude target product (adduct containing 1 molecule of ethanol) [mp50-82℃; TLC (see above)
Rf0.50-0.56 (thin), 0.56-0.66)] was obtained (34.5% yield based on dithiocarboxylic acid). Example 12 The hot ethanol solution of the crude target product in Example 11 was treated with activated carbon, and the crystals precipitated when cold were collected. It was dried under reduced pressure to obtain the above-mentioned identified sample (mp 119-121°C). Example 13 A system consisting of 0.03 mol (4.7 g) of 4-methylimidazole-5-dithiocarboxylic acid and 0.06 mol (3.2 g) of acrylonitrile was heated at 70 to 80°C for 4 hours.
After maintaining the temperature, the contents were concentrated under reduced pressure, and the residue was 60ml.
The extracted liquid was extracted with hot acetone, and the extracted liquid was treated with activated carbon.
2.3 g (yield 36.3% based on dithiocarboxylic acid) of Rf0.30-0.40] were obtained. Example 14 The crude target product of Example 13 was treated as in Example 2 to obtain the identified sample (mp 145-147°C). Example 15 A system consisting of 0.03 mol (5.2 g) of 2,4-dimethylimidazole-5-dithiocarboxylic acid and 0.06 mol (3.2 g) of acrylonitrile was heated for 5 hours.
After keeping the temperature at 70-80℃, the contents were dried under reduced pressure, and the dried product was reconsolidated with acetone to obtain the crude target product [mp146-151
°C; TLC (mentioned above) Rf0.38-0.48, 0.70-0.74 (extremely thin)
%) Got. Example 16 The crude target product of Example 15 was treated as in Example 2 to obtain the identified sample (mp 156-158°C). Example 17 A system consisting of 0.03 mol (5.6 g) of 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid, 12 ml of DMF, and 0.06 mol (3.2 g) of acrylonitrile was kept at 70 to 80°C for 2 hours. The contents were concentrated under reduced pressure, and the residue was reconsolidated with ethanol to obtain the crude target product [mp159-162℃; TLC (mentioned above) Rf0.45-0.55]
4.7g (yield based on dithiocarboxylic acid: 65.5%) was obtained. Example 18 The crude target product of Example 17 was treated as in Example 4 to obtain the identified sample (mp 163-165°C). Example 19 2-phenyl-4-methylimidazole-5-
After keeping the system consisting of 0.03 mol (7.0 g) of dithiocarboxylic acid and 0.06 mol (3.2 g) of acrylonitrile at 70-80°C for 2 hours, the contents were concentrated under reduced pressure and the residue was extracted with 60 ml of hot acetone. Then, the extract was treated with activated carbon, the resulting liquid was concentrated under reduced pressure, the acetone solution of the residue was passed through a layer of activated clay, the passed liquid was dried, and the dried solid was reconsolidated with ethanol to obtain the crude target product [mp143 ~152℃; TLC (mentioned above) Rf0.53~0.60
(very thin), 0.60-0.70] (26.7% yield based on dithiocarboxylic acid) was obtained. Example 20 The crude target product of Example 19 was treated as in Example 4 to obtain the identified sample (mp 153-156°C).

Claims (1)

[Claims] 1 General formula [Formula] [In the formula, R ₂ is 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, and R ₄ is a Represents a hydrogen atom or a methyl group. ] A general formula characterized by an addition reaction between an imidazole dithiocarboxylic acid compound and acrylonitrile represented by [However, in the formula, R ₂ and R ₄ are the same as above. ] A method for synthesizing an imidazole dithiocarboxylic acid cyanoethyl ester compound.