JPS6019769A - Synthesis of imidazole dithiocarboxylic acid ester compound - Google Patents

Abstract

PURPOSE:To produce the titled compound useful as an intermediate of agricultural chemicals and pharmaceuticals, from an easily available raw material, in high yield, by condensing an imidazole-dithiocarboxylic acid compound with an alkylating agent. CONSTITUTION:The compound of formula II is produced by the condensation reaction of (A) the imidazoledithiocarboxylic acid compound of formula I (R2 is H, methyl, ethyl, undecyl, heptadecyl or phenyl; R4 is H or methyl) with the alkylating agent of formula R5-Z (R5 is methyl, ethyl, propyl, butyl, lauryl or benzyl; Z is halogen or 1/2SO4 group) (e.g. methyl iodide, propyl chloride, etc.) preferably removing the hydrogen halide or monoalkyl sulfate from the system with the acceptor of hydrogen halide or monoalkyl sulfate. The starting compound of formula I is synthesized from the corresponding imidazole compound and carbon disulfide.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for synthesizing an imidazole dithiocarboxylic acid ester compound, and is characterized by carrying out a condensation reaction with an alkylating agent represented by the imidazole dithiocarboxylic acid compound shown in detail. This invention relates to a method for synthesizing an imidazole ditheocarboxylic acid ester compound represented by the general formula.

The imidazole dithiocarboxylic acid compound and its alkali gold Jg salt, which are the starting materials for the method of the present invention, are
As shown in Japanese Patent No. 17696, it can be easily obtained in high yield from the corresponding parent imidazole and carbon disulfide.

When the starting material imidazole ditheocarboxylic acid is subjected to a condensation reaction with an alkylating agent, a hydrogen halide salt or monoalkyl sulfate of a nuclear dithiocarboxylic acid ester is first produced, and then the hydrogen halide or When a monoalkyl sulfate is reacted with a hydrogen halide acceptor or a monoalkyl sulfate acceptor, the desired dithiocarboxylic acid ester is obtained.

1 In addition, when the starting material imidazole dithiocarboxylic acid and an alkylating agent are subjected to a condensation reaction in the presence of a hydrogen halide acceptor or a monoalkyl sulfate acceptor, the target dithiocarboxylic acid varnish 6-R is produced according to the following reaction formula. When the alkali metal salt of ibadazole dithiocarboxylic acid is subjected to a condensation reaction with an algylating agent, the desired dithiocarboxylic acid ester is similarly obtained according to the reaction formula shown below.

The alkali metal salts of imidazole dithiocarboxylic acids are primarily the sodium and potassium salts. When imidazole and carbon disulfide are reacted in the presence of an alkali hydroxide to synthesize imidazole dithiocarboxylic acid, the ditheocarboxylic acid ar-7-alkali metal 1 is first produced, so the imidazole dithiocarboxylic acid ester is directly synthesized as it is. starting materials and 11. It can be used as

Since the dithiocarboxylic acid easily forms with the basic ion BQ to give the dithiocarboxylic acid B as shown in the reaction formula shown below, the dithiocarboxylic acid B can also be used as a starting material.

The basic ion BΦ used is 1.1Φ, N
ae, KΦ, Oa”e%IlaΦ0, MgeΦ, znΦ
Φ, 0uee%MnΦΦ, coΦΦΦ, NJ"■, I"
86: IΦΦ Hgefil, SnΦΦ, PbΦΦ, N
ITs, organic ammonium oxides, ions, etc.

As mentioned above, the dithiocarboxylic acid easily forms salts with various metal ions to form various bases, but the use of these metal salts as starting materials is more difficult than the use of sodium and potassium salts. From an economic standpoint, I can't think of a separate establishment.9. do not have.

The hydrogen halide or monoalkyl sulfate acceptor used in the present invention is of the very general type, which reacts with the hydrogen halide or monoalkyl sulfate to give a neutralized salt. You can use whatever you have. They are as shown below.

NHs, NH4OH, LLOH, NaOH, KOH
,Oa(OH)mushroom,na(oH)m,Mg(oH
)m, LICOs, Nag COx, Kjoos
.

Oac! Os, B a C! Os%Mg,C!
Os s OHs Co ON a, OHs OO
O%Fit; tertiary amines such as iN and pyridines,
Quaternary ammonium hydroxide (e.g. 'l'rlton
B e ) Go.

The alkylating agents used in the present invention are alkyl halides, benzyl halides, and dialkyl sulfates, and alkyl groups with various carbon numbers can be used, from lower alkyl groups to higher alkyl groups. Regarding the type of halogen atom, any of chlorine atom, bromine atom and iodine atom can be used.

9- Representative alkylating agents are shown below.

Methyl iodide, ethyl iodide, propyl chloride, -propyl, propyl iodide, butyl chloride, butyl bromide, butyl iodide, lauryl t3, lauryl bromide, benzyl chloride, benzyl bromide, benzyl iodide, dimethyl Sulfuric acid, diethyl sulfate, etc.

Considering the reaction between the active hydrogen of the solvent and the alkylating agent, J
η (Theoretically, it is thought that the solvent used in the 11 reaction should be one that does not have active hydrogen [7], but experimental results always show that 17 such a prediction is not accurate, and water and alcohol are preferred. It has been found that solvents can also be used satisfactorily.Therefore, restrictions regarding solvents are considered to have no significant meaning.

Representative solvents suitable for the practice of this invention include water, methyl alcohol, ethyl alcohol, dimethylformamide,
These include dimethyl sulfoxide, 7'cetonitrile, acetone, acetic acid, and pyridine.

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 once the reaction has progressed, the heat generation weakens, so heating is required under counter pressure. This is a method of temperature control when shortening the reaction time is taken into consideration. The reaction temperature in this case 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°C is sufficient. In order to slow down the heat generation, it is desirable to gradually add the alkylating agent to the reaction system. It is of course possible to conduct the reaction for a long time under water 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 for separate pressurization.

Regarding the molar equivalent relationship of imidazole dithiocarboxylic acid or its alkali metal base, alkylating agent, and hydrogen halide acceptor or monoalkyl sulfate acceptor, 1 molar equivalent of the starting material dithiocarboxylic acid or its base is 1
Molar equivalents or 1-11-molar amounts of alkylating agent and acceptor 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.

Ru.

Various imidazole dithiocarboxylic acid 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 ethyl ester Physical propertiesOrange crystals,) Neutral. m, p, 140-145'C (acetone).

Soluble in methanol, ethanol, acetone, acetic acid, chloroform, toluene and DMEIO. Poorly soluble in water. T.L.
O(Silica G% 0HO)s/MeOH=10
/1 volume ratio, 3 colors): Rfo, 55-0.43°,:! r: 105B (Th1 absorption, vc-s).

NMR (OFSOOO) (): δB, 76, d, 1
)T (proton at 2nd position); 8.02, (1, IH (proton at 4th position); 3.50, q, 2H (methylene proton of ethyl group).

Mass: m/e 172 (M"), 144
(M" 0Ht(Jb+I(), 1 f 1 (M"-
BOH Mushroom CjH 謬).

Imidazole-4-dithiocarboxylic acid benzyl ester Physical properties Orange crystals. neutral. m I) 144-146℃ (acetone) methanol, ethanol, acetone, acetic acid, chlorine
- Soluble in loloform and benzene. Poorly soluble in water.

TI, (l supra): RrO, 30~0.40°C2Ba
r: Tomiro 46 (first absorption, vc -8).

NMR (aFscoo++): J8.79, a, I
H (2KL proton); e, n 3.8, I H
(Proton at 4th position); Otsu 56, day, 5H (phenyl proton); 4.67, a, 2H (methylene proton of benzyl).

Mas8: m/e 2! S4 (M”), 20t
(v+-5H), 145 (M◆-01h -Ph)
, + 11 (M” 80Ht Ph1), 91.77
゜2-Methylimidazole-4-diteocarboxylic acid ethyl ester Physical properties Red-orange crystals. neutral. In, T1. +15~117'O(
acetone).

Methanol, ethanol, acetone, acetic acid, chloroform, toluene and (jDMS OKtW solution. Dissolved in water.

TLO (supra): Rfo, 45-0.55°ν2: 1072 (first absorption, c-8).

NMR (CPs 000)T): δ7.87.8.1
E (4-position proton); 3,47.4%2]H (methylene proton of ethyl group); 2.78, B, 3H (2-position methyl proton); 1.44, t, 3FT (methyl of ethyl group); proton).

Maas: m/e 186 (M"), 15B (M"-
C City OHs +H), 125 (M” BOH*(jI
h).

2-Methylimidazole-4-dithiocarboxylic acid butyl ester Physical properties: Orange crystals. neutral. mp, 107-110℃ (acetone)
.

Methanol, ethanol, acetone, acetic acid, ri-15- Roloform, toluene and D14S OKb1 solution.

Poorly soluble in water. TTJO (mentioned above): Rfo, 40-0.50
゜p, :! r: 1075 (No. 21115/, b
pc = s 1°NMR (OFI 0OOH1: J
Otsu 85, s, In (4th proton); 3.49, t, 2
n (butyl group α-methV7); 2-78, s
, 3H (2-position methyl proton); 1,97-1.53,
m, 4H (β-gamma-methylene proton of butyl group);
1°On, t, 311 (terminal methyl pro-I of butyl group
·hmm).

Mass: m/e 214 (M”), 181
(M+-8-■), 158 (M"-CIlsCH fable 01
1xO11a+H), 125(M”-BCH amount CI 鵞C
Hs OHj ), 44 (:a-s).

2-Methylimidazole-4-diteocarboxylic acid lauryl ester physical orange crystal. neutral. m, p, 104-10 B'C (acetone).

Methanol, ethanol, acetone, acetic acid, chloroform, toluene and DMSOKtiT solution. Insoluble in water. T.L.
C (mentioned above): RfO, 5 (1 to 0.60° i=r: 1
ots8(4th absorption, νCC60°NMR((!Fs
coo) T): J Otsu 85.8.1■ (4-position proton); 3.49, t, 2H (α-methylene proton of lauryl group); '2-74% 8,! i H (2-position methyl proton); 1.86, m, 2H (β of lauryl group)
-methylene proton); 1.34% m s 1
8n (intermediate methylene proton of lauryl group); 0, 89
, m -3III (terminal methyl proton of lauryl group).

Mass: m/e 526 (M'), 295 (
M+-8-■), 158(M”-OHm (C1h
)+@OH* +H), 125(M” SOH*(OH
j) se OHj ), 44 (:0-8).

2-Ethylimidazole-4-dithiocarboxylic acid ethyl ester 17- Physical properties Orange crystals. neutral. m, p, IO8-110″C (acetone.

Soluble in methanol, ethanol, acetone, acetic acid, chloroform, ;-luene and UDM 80K. Poorly soluble in water. T
I, O (mentioned above): RfO, 50~0.60°p, :!
r: 1084 or rj, 1104B (114 absorption, pc-
s).

NMR (OFs 0OOH): J 7.8B, 6.
1H (4-position proton); 3.4B, q, 2H (methylene proton of mercaptoethyl group); 3.14, q, 2H
(Methylene proton of 2-position ethyl group) = 1.4 q
, t, 3) ((methyl proton of mercaptoethyl group)
; 1.44, t, 5H (methyl proton of 2-position ethyl group).

uass: m/e 200 (M'), 172
(M”-OHm OFIm ++r), +39 (M
” -8OTTs 0)1i)1.a,a (:a-
s).

18- 2-Undecylimidazole-4-dithiocarboxylic acid ether ester structural formula% Formula% (Orange crystals. Neutral. m, p, 80-85'C (acetone)
.

Soluble in methanol, ethanol, acetone, acetic acid, chloroform, toluene and DM 80K. Insoluble in water. T1
10 (mentioned above): ufo, 70-0.80°νsr: 10
6B (third absorption, van-s).

NME (OFs Coon): J7.85, Sun.
1■ (4-position proton); 5.46, q, 2H (methylene proton of ethyl group); 3.09, t, 2B (α-methyV7 proton of 2-position Kundecyl group); 1.9o, m,
2'H (β-methylene proton of undecyl group at 2-position);
1.4B, t, sH (methyl proton of ethyl group); 1
．． 32, m, 16B (intermediate methylene proton of undecyl group at 2-position); 0.88, m, 3H-19- (terminal methyl proton of undecyl group at 2-position).

Mass: m/e 326 (M'''), 298 (
M” CjIh CHs ), 297 (M” OHm
OH heavy 10H), 293 (M"-8-H), 265 (
M”BGHgCTb), 114(:0-8).

2-Hebutadecyl-4-dithiocarboxylic acid ethyl ester Physical properties Yellow-orange crystals. neutral. m, p, 90-95°C (acetone)
.

Soluble in methanol, ethanol, acetone, acetic acid, chloroform, toluene and DMSO. Insoluble in water. T L
O (mentioned above): pfO, 75-a85゜shi: IQ7
2 (third absorption, C-8).

NMR(OFsOOOH): J7.85.6.
1H (4-position proton); 3.4S, 4% 2H (methylene proton of ethyl group); 3.09, t, 2n (α-methylene proton of 2-position heptadecyl group); 1.9[), m
, 2a (β-methylene proton of heptadecyl group at 2-position)
; 1.44, t% AH (methyl proto7 of ethyl group);
1.52, In, 281 ((intermediate methylene proton of heptadecyl group at 2-position); 0.8B, m, 5H (terminal methyl proton of heptadecyl group at 2-position).

Mass: m/e 410 (M◆), 582 (
M" CL OHs 10H), !181 (M◆-CH
I OHs), 549 (M” 5OFb OHs
).

2-phenylimidazole-4-dithiocarboxylic acid benzyl ester Physical properties Orange crystals. neutral. m, p149-151”C (acemethanol, ethanol, acetone, acetic acid and DIN S
Soluble in O. Poorly soluble in water. Tll0 (mentioned above): Rf 0.
65-0.75.

C:,! r: 1070 (second absorption, ν cm).

NMR (OFs CoOH): '8.03%
as I H (proton at 4th position); a, no ~7.50
, m, 5H (2-position phenyl proton); 7.34, s,
5M (phenyl proton of benzyl group); 4. tS8,
s12'H (methylene proton of benzyl group).

Masa: m/e 3111 (M"), 277
(M”-BH), 219 (M”-OH heavy ph), 187
Oc-aag* ph), 104.91.77.4
4゜4-Methylimidazole-5-dithiocarboxylic acid methyl ester physical properties 22- Orange crystals. neutral. m-T), 194-196°C (acetone).

Methanol, ethanol, acetone, acetic acid, chloroform, toluene and DMSO! lc soluble. Poorly soluble in water. TTJO (mentioned above): ufo, 36~0.46°ν,:
”!r: 105B (first absorption, C-θ].

NMR ((31Fs C00H): δ8.5B, s, 1
H (2-position proton); 2.9 L s, 3H (methyl proton of mercaptomethyl group); 2.87, s,
3H (4-position methyl proton).

Mass: m/e 172 (M”), 157
(M"-0Hs), 125 (M+-EIO) 1m
).

4-Methylimidazole-5-dithiocarboxylic acid ethyl ester Physical properties Red-orange crystals. neutral. m, pla 5~1 sy'c
(Amethanol, ethanol, acetone, acetic acid, chloroform, toluene and chloride) MEI OK Soluble. Tei II dissolved in water. TLC (mentioned above): FlfO, 40-0.50
゜v 2=, '106' (k 1 absorption, vc-
s).

NMRrOFs oooH): δ861, o, 1x ((
2-position proton); 3.5M, q, 211 (methylene proton of ethyl group); 2-87.8.3) T (methyl proton 4-position); 1.49.1:, 5H (methyl proton of ethyl group ).

Mass: m/e 1136 (M”), 15
B (M" OTh 0Hs-H), 125 (M'
SCH*OHs), /14(:0-8).

2.4-dimethylimidazole-5-dithiocarboxylic acid propyl ester Physical properties Orange crystals. neutral. m, p, 127-129'0 (acetone).

Soluble in methanol, ethanol, acetone, acetic acid, chloroform, toluene and DMsoK. Poorly soluble in water. T TJ
O (mentioned above): Rfo, 42~0.52゜νgor: 10
s5(vc-6).

NMR (OFjOOOH): δ3.47, t, 2a (
α-methylene proton of propyl group); 2.79, s,
5H (2-position methyl proton); 2.71.8, Am (4
position methyl proton); 1.83, m, 2a (β-methylene proton of propyl group); 1.10, t, AB (methyl proton of propyl group).

Mass: m/a 214 (M”), 172 (M
”-OH Kura OH 禦CHI 11 (), 139 (M” S
O'&OHs (jHs), 44 (:c-s).

2-Ethyl-4-methylimidazole-5-dithiocarboxylic acid ethyl ester Physical properties 25- Orange crystals. neutral. mp, 1!5Q to 132°C (acetone).

Methanol, ethanol, acetone, acetic acid, chloroform, toluene, benzene and DMSO
K-town style. Poorly soluble in water. Tll0 (mentioned above): nfr), 5
6~0.66゜p, :! r: 1055 (vcw-a).

NMR (ODOJ-): a 3.55.4%21T
(Methylene proton of mercaptoethyl group); 2.70
, q, 2H (methylene proton of 2-position ethyl group); 2.
59.8.3■ (4-position methyl proton); 1.56, t
llH (methyl proton of mercaptoethyl group); 1.
27, t, 5H (methyl proton of 2-position ethyl group).

Mass = m/e 214 (M◆), 1(36(
M” OHm OSs +H), 181 (M+-5-
i), 153 (M” 80Hj OHs 1゜2-
Ether-4-methylimidazole-5-dithiocarboxylic acid benzyl ester structural formula Yellow-orange crystals. neutral. m, p, 109-110°C (acetone).

Soluble in methanol, ethanol, acetone, acetic acid, chloroform, carbon tetrachloride, benzene and toluene. Poorly soluble in water.

TLO (mentioned above): Rfo, 60~0.70° C2! r:
to4o or 1020 (second absorption, νC=8).

NMR (0DOji): a 7.30, m, 5
m (7! = le proton); 4.57, s, 2H (methylene proton of benzyl group); 2.69, cl, 2H (
methylene proton of 2-position ethyl group); 2.5B, s, 5
H (4-position methyl proton 3; 1.29, t13■ (2-position ethyl group methyl proton).

Mass: m/r 276 (M◆), 243 (M
◆-8M), 185-27-1c-cutph), 15!5 (M'-80H1p
h), 91° 2-Undecyl-4-methylimidazole-5-diteocarboxylic benzyl ester Physical properties Red viscous liquid. neutral.

Soluble in methanol, ethanol, Flt+acid, chlorophoric benzene and toluene. Insoluble in water. TLC (mentioned above)
:Rfo, 70~0.80゜p, :! r:1050 (
vc'-e).

NMR (0'Fs Coon): a 7.56, day, 5xr (phenyl proton) i4.69, θ, 2n (
methylene proton of benzyl group); 3.07, t, 2
H (α-methylene proton of undecyl group at 2-position); 2.
77, s, 3H (4-position methyl proton); 1.87,
m, 2H (β-methylene proton of undecyl group at 2-position)
11.32, m, 16u (intermediate methylene proton of undecyl group at 2-position); 0.89, m% 5H (terminal methyl proton of undecyl group at 2-position).

Mass: m/e 402 (M dispute), 369
(uo-Fl-H),! + 11(vr -OHmP
h 1.279 (M”-8OH snow ph), 91.44
゜2-Phenyl-4-methylimidazole-5-dithiocarboxylic acid ethyl ester orange crystals. neutral. m, p, 162~165”O(Fi
tO)I).

Soluble in methanol, ethanol, acetone, acetic acid, chloroform, toluene and DMsO. Insoluble in water. T110
(mentioned above): Rfo, 65~0.75°v:,! r:
1068 (second absorption, pc-s).

N14R(O12aooH): 87.97-7.60,
m, sn (phenyl proton); 3.54, (1% 2
H (methylene proton 1 of ethyl group -29=; 2.91, θ, 51 (methyl proton at 4th position); 1.50, t, 3H (methicib 01-one of ethyl group).

Mass: m/e2620P1.234 (M”OH
s CI(s +H1,201(M”80Iis n
US), 104.77.44゜Example 1 A reaction vessel equipped with a reflux condenser was placed on a magnetic stirring hot plate, and 0.03 mol of imidazole-4-dithiocarboxylic acid (4-3gr1, hydroxylated) Calcium 0.015 mol (1
, 1g) and 20 liters of water, then 0.03 mol (4.7 g) of ethyl iodide was added at once to the entire room temperature while stirring, and the system was maintained at 60-70''C for 2 hours before precipitation. Separate the crystals, re-crystallize the crystals with acetone, and obtain the crude target product (m, p, IS 0-140°C; TLO (silica G1 chloroform/methanol-10/1 volume ratio, 1 snow color development) Rfo, 35- 0.44]!!, 8g (yield based on dithiocarboxylic acid: 73.6%) was obtained.

Example 2 The hot acetone solution of the crude target product of Example 1 was treated with activated carbon 30-30%, and the crystals precipitated from the furnace liquid when cold were added.
The addend crystal was re-solidified twice with acetone, and the identified sample (m
, p, 140-143°C).

Example 3 Imidazole-4-dithiocarboxylic acid 0.05 mol (4
-5g), ethanol 12s/and Hensyl Bromide 0,0
A system consisting of 3 moles (5.1 g) of 3 strands was heated for 2 hours at 75 ~
After keeping the temperature at 80°C, a small amount of precipitated crystals was separated, the furnace solution was made basic with aqueous ammonia, and then dried under reduced pressure. , 140~
145°C; Tll0 (1ufO130 to 0.40 as mentioned above)
) was obtained (yield 79.0% based on ditheocarboxylic acid).

Example 4 The crude target product of Example 3 was treated as in Example 2 to obtain the identified sample (m, p, 144-146°C).

Example 5 2-methylimidazole-4-dithiocarboxylic acid 0.0
3 mol (4.7 g), potassium carbonate 0.015 mol (2.1 g), water 20 m and ethyl iodide 0.0-70
'After maintaining the CIC, remove the water layer from the gradient to create a candy-like substance.
The candy-like substance was reconstituted with acetone 17, and the crude target substance (m, p, 1
[1y ~ 11 s'C; T LO (mentioned above) Rt
0-45 to 0.55) was obtained (yield 68.1% based on dithiocarboxylic acid). Example 6 The heated acetone solution of the crude target product of Example 5 was treated with activated carbon. The crystals precipitated when cold are counted, the crystals are reconsolidated with acetone, and the identified sample (m, p, 115
~111G) was obtained.

Example 7 2-methylimidazole-4-dithiocarboxylic acid 0.0
3 mol (4.7 g'), sodium acetate 0.03 mol (
2,5G<), acetic acid 20s/and ethyl iodide 0°05
After keeping the system consisting of 4 moles (4.7 g) at 70°C for 3 hours, the precipitated crystals were separated, the furnace liquid was dried under reduced pressure, the dried product was washed with water, and then reconsolidated with acetone to obtain the crude target product. (m, p, 1
07-115°C; TIJO (mentioned above) Rfll, 45-0
．． 55) (1.7 g of dithiocarboxylic acid yield: 3064
%) Got.

Example 8 2-methylimidazole-4-dithiocarboxylic acid 0.0
3 mol (4.7 g), potassium hydroxide 0.05 mol (1
, 7g), 20 parts water, and 0.03 mol (4.1 g) of n-butyl bromide were heated at 75-80°C for 3 hours.
After maintaining the temperature at 109'C;T
LO (mentioned above) Rfo, 40-0, 50) was added to 4.5 g (
A yield of 70.0% for dithiocarboxylic acid was obtained.

- Example 9 The crude target product of Example 8 was treated as in Example 6 to obtain the identified sample (m, p, 107-110°C).

Example 10 2-methylimidazole-4-dithiocarboxylic acid 0.0
3 mol (4.7 g), sodium hydroxide 0.03 mol (
After heating under reflux (liquid temperature: 80°C) for 3 hours, the system was cooled to separate the precipitated crystals. The p-removal crystals were washed with water, and then reconsolidated with acetone to obtain the crude target product (m, p, 104-108°O
; 8.2 g (83.8% yield based on dithiocarboxylic acid) of T Tr O (previously described) Rfo, 50-0.60) was obtained.

Example 11 The original product of Example 10 was treated as in Example 6 to obtain the identified sample (m, p, 104-108°C).

Example 12 2-ethylimidazole-4-dithiocarboxylic acid 0.0
3 moles (5.2 g), magnesium carbonate 1.5 g 1 water 2
After a system consisting of 0d and 0.03 mol (4.7 g) of ethyl iodide was kept at 60 to 70°C for 2 hours, the aqueous layer was decanted to obtain a candy-like substance. was reconstituted with acetone to obtain the crude target product (m, p, 10!1~109℃; TLO
4.0 g (62.5% yield based on dithiocarboxylic acid) of (Info, so ~ 0.60) was obtained.

Example 15 The crude target product of Example 12 was treated as in Example 6 to obtain the identified sample (m, p, 108-110''C).

Example 14 2-undecylimidazole-4-dithiocarboxylic acid 0
．． 025 mol (7.5 g), sodium hydroxide 0.02
A system consisting of 5 mol (1.0 g), ethanol 20 s / and ethyl iodide 0.025 mol (!i, 9 g) was kept at 60 to 70 ° C. for 2 hours, and the contents were dried under reduced pressure.
After washing the dried product with water, it was reconstituted with acetone to obtain the crude target product (m,
p, 77-82°C; TLO (supra) Rfo, 70-0.
80) (yield 85.9% based on dithiocarboxylic acid)
) got it.

Example 15 The crude target product of Example 14 was treated as in Example 6 to obtain the identified sample (m, p, 80-B''r'C).

Example 16 2-heptadecyl imidazole-4-dithiocarboxylic acid 0.015 mol (5.7 g), calcium carbonate 0.00
75 mol (0.75 g), dimethylformamide 20s
After keeping the system consisting of 4 layers of Z and 0.015 mol (2°-35-3 g) of ethyl iodide at 65 to 70°C for 4 hours, the precipitate was separated from the furnace] 2. The p liquid was concentrated under reduced pressure and the remaining The ammoniacal methanol solution of the product was dried under reduced pressure, and the dried product was washed with water and reconsolidated with acetone to obtain the crude target product (m, p, 85~
90'(3; T LO (supra) Rf O.

60-0.75 (very thin), 0.75-0.85) (yield 91% based on dithiocarboxylic acid) was obtained.

Example 17 The crude target product of Example 16 was treated as in Example 6 to obtain the identification assay (m, p, 9 [1-93°C) described above.

Example 18 2-phenylimidazole-4-dithiocarboxylic acid 0.
0.03 mol (6.6 g), triethylamine 0.03 mol (3.0 g), ethanol 20 m and benzyl chloride 0.
, 03 mol (3.8 g) of 4 people was heated under reflux for 2 hours (liquid temperature 80°C), and the contents were dried under reduced pressure. Object (n
+, p, 155-145'C; T LC (mentioned above) Rf
0.68-0.77, 0.80-0.82 (extremely thin)] was obtained (88.8 g of dithiocarboxylic acid yield: 94%).

Example 19 The crude target product of Example 18 was treated as in Example 2 to obtain the identified sample (m, p, 149-151YE).

Example 20 4-methylimidazole-5-dithiocarboxylic acid 0.0
3 moles (4-7 g), 0.03 moles of sodium hydroxide (
1.2 g), 20-20 g of water and 0.03 mol of methyl iodide (
After keeping the system consisting of 4.5 g) at 40°C for 2 hours, the precipitated crystals were separated, and the crystals were reconsolidated with acetone to obtain the crude target product (m, p, 185-192'C; TLO (previously). )
2.2 g (42.6% yield based on dithiocarboxylic acid) of Rfoj6-0.46) was obtained.

Example 21 The crude target product of Example 20 was treated as in Example 6 to obtain the identified sample (m, p, 194-191S'O).

Example 22 4-methylimidazole-5-dithiocarboxylic acid 0.0
3 moles (4-7 g), 20 g of acetone? After heating and refluxing the 37-system consisting of 0.05 mol (3.8 g) of dimethyl sulfate and 0.05 mol (3.8 g) of dimethyl sulfate for 5 hours (inner temperature 57°C), the contents were concentrated under reduced pressure, and the residue was extracted with methanol. After making it basic with aqueous ammonia, it was dried under reduced pressure, and the dried product was washed with water and reconsolidated with acetone to obtain the crude target product (m, p, 170
~182°C; TLO (mentioned above) Rfo, 05~0.10
(Extremely thin, 0.56-0°46) yield of 1.86 (yield based on dithiocarboxylic acid 34.9%).

Example 23 4-methylimidazole-5-dithiocarboxylic acid 0.0
A system consisting of 4 people consisting of 3 moles (4.7 g), 0.05 moles (2.0 g) of 25% aqueous ammonia, 20 gd of water, and 0.03 moles (4.7 g) of ethyl iodide was heated at 60 to 70 °C for 2 hours.
After maintaining the temperature at
0 (mentioned above) RfOj5-0.40 (extremely thin), 0.4
0 to 0.50) to i2g (yield of dithiocarboxylic acid: 5
7.3%).

Example 24 The crude target product of Example 23 was treated as in Example 6 to obtain the identified sample (m, p, 185-187''C).

Example 25 4-methylimidazole-5-dithiocarboxylic acid 0.0
After maintaining the system at 65 to 70°C for 3 hours, the contents were dried under reduced pressure. After washing the dried product with water, it was reconsolidated with acetone to obtain the crude target product (m, p, 175-185°C: TILO (previously mentioned) TI
fO45~0.40 (extremely thin), 0.40~O,S
3.2 g of O) (yield 57.3% based on dithiocarboxylic acid)
I got it.

Example 26 2.4-dimethylimidazole-5-dithiocarboxylic acid 0.03 mol (5.2 g), sodium carbonate 0.0
15 mol (1.6 g), methanol 20 w1 and geochemical n
- A system consisting of 0.03 mol (2.4 g) of propyl was kept at 60 to 65°C for 3 hours, and the precipitated crystals were separated by r.
The furnace liquid was dried under reduced pressure, and the dried product was reconsolidated with acetone to obtain the crude target product (m, p, 114-121'C; Tll0 (mentioned above) Ef
o, 05-0.10 (extremely thin) -59- 〇, 42-n, 52.1 was obtained in an amount of 2.0 g (yield 51.1% based on dithiocarboxylic acid).

Example 27 The hot acetone solution of the crude target product in Example 2 was treated with activated carbon, and the crystals precipitated from the gill 71 car f1 liquid when cold were counted.
The previously identified sample (m, p127-129°C) was obtained.

Example 28 0.057 2-ethyl-4-, methylimidazole-5-diteocarboxylic acid (5.6 g), 12 m dimethylformamide and 0.0 ethyl iodide! i mole (4.7 g
) was kept at 70°C for 2 hours, and the contents were dried under reduced pressure. 'C;TLO(
Previous) Rf (LOO (acidic substance), 0.56 to 0.66
) (yield 68.2% based on dithiocarboxylic acid)
I got it.

The ammoniacal methanol solution of the hydroiodide salt was dried under reduced pressure, and the dried product was washed with water and reconsolidated with acetone to obtain the crude target product (mp, 127-150°C; 'rL).

(mentioned above) Rf 0.56~0.66)! i, Og
(yield of 46.7% based on dithiocarboxylic acid).

Example 29 The crude target product of Example 28 was reconstituted twice with acetone to obtain the aforementioned identified sample (m, 1.13 D to 132''C).

Example 30 0.03 mol (6.5 g) of 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid sodium salt, 20 ml of ethanol and 0.03 mol (4.7 g) of ethyl iodide
) was kept at 65-70°C for 4 hours, the contents were dried under reduced pressure, the dried product was washed with water and recondensed with acetone to obtain the crude target product (m, p127-1'51 ℃；rIJ
4.2 g (yield 65.4% based on sodium ditheocarboxylate salt) of Rfo, 56-0, 66) was obtained.

Example 31 0.03 mol (5,6 g) of 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid, 12 s/d of dimethylformamide and 0.03 mol (4,6 g) of diethyl sulfate
After maintaining the three-part system at 50 to 7041-"C for 2 hours, the contents were concentrated under reduced pressure, the ammoniacal methanol solution of the residue was dried under reduced pressure, the dried product was washed with water, and then reconsolidated with acetone. and coarse target material (m, p125-150
'C; TTJO (mentioned above) Rf 0.56 to 0.66]
3.6 g (yield based on dithiocarboxylic acid: 56.1%) was obtained.

Example 32 2-ethyl-4-methylimidazole-5-dithiocarboxylic acid 0.05 mol (5,6 g>, dimethyl sulfoxide 12 s/l"lfi benzyl 0.05 mol (x, s
After maintaining the system consisting of 321 of g) at 75 to 80" CVC for 2 hours, the system was cooled, the precipitated crystals were separated, and the crystals were reconsolidated with acetone to obtain the target hydrochloride (m).

p, 202~210°C 1TLo (mentioned above) Rfo, 50~
0.60 (very thin 1), 0.60 to 0.70) to 5.
7 g (61% yield of dithiocarbon) was obtained. The ammoniacal methanol MM of the hydrochloride was dried under reduced pressure.

After washing the dried product with water, it was reconstituted with acetone to obtain the crude target product (m,
p, 105-109°C; TLO (mentioned above) 'Rf 0°60-0.70) was added to 3.4 g (ditheocarboxylic acid yield Example 35 The crude target product of Example 52 was treated as in Example 6, The previously identified sample (m, p, IO 9-111''o) was obtained.

Example 54 0.05 mol (9,4 g) of 2-cundecyl-4-methylimidazole-5-dithiocarboxylic acid, 0.03 mol (3,8 g) of dimethylformia and 0.03 mol (3,8 g) of benzyl chloride
After keeping the system consisting of the three components in g) at 70 to 80°C for 2 hours, the contents were concentrated under reduced pressure, the residue was dissolved in ethanol, made basic with aqueous ammonia, and the solution was concentrated under reduced pressure. The extracted residue was extracted with water, the toluene solution of the extracted residue was passed through a layer of activated clay, and the permeate was concentrated under reduced pressure to obtain the crude target product [red viscous liquid; TLO (mentioned above) R].
fo, 70-0.80) (yield 41% based on dithiocarboxylic acid) was obtained.

Example 35 A toluene solution of the crude target product of Example 34 was passed through a layer of activated clay, and the permeate was concentrated under reduced pressure to obtain the identified sample described above.

-43 Example 36 2-phenyl-4-methylimidazole-5-cythiocarboxylic acid 0.03 mol (7.0 g), sodium carbonate o
, ois mol (1.6 g), acetonitrile 20 g/and ethyl iodide 0.05 mol (4.7 g) was kept at 60 to 70°C for 3 hours, and the contents were dried under reduced pressure. After washing the dried product with water, it was reconsolidated with ethanol to obtain the crude target product (m, p, 150-158"C; TLO (mentioned above) R
fO147~0.57 (very thin), 0.65~0.7
5) (38.2% yield based on ditheocarboxylic acid)
I got it.

Example! i7 The heated ethanol solution of the crude target product of Example 36 was treated with activated carbon, the resulting furnace liquid was dried under reduced pressure, the dried product was reconsolidated twice with ethanol, and the a7ton solution of the crystals was dissolved in activated clay. The filtered liquid was dried under reduced pressure, and the dried product was reconsolidated with ethanol to obtain the identified samples (m, p).

162-165°C).

Claims (1)

[Scope of Claims] A method for synthesizing an imidazole dithiocarboxylic acid ester compound represented by the following formula 2, which comprises carrying out a condensation reaction with an alkylating agent represented by the formula 3. (2) The imidazole according to claim (1), in which the imidazole dithiocarboxylic acid compound and an alkylating agent are subjected to a condensation reaction, and dehydrohalogenation or monoalkyl sulfate is removed using a hydrogen halide acceptor or a monoalkyl sulfate acceptor. Method for synthesizing dithiocarboxylic acid ester compounds. (8) The method for synthesizing an imidazole dithiocarboxylic acid ester compound according to claim (1), in which an imidazole dithiocarboxylic acid compound and an alkylating agent are subjected to a condensation reaction in the presence of a hydrogen halide acceptor or a monoalkyl sulfate acceptor. . (4) A method for synthesizing a special carboxylic acid compound in which an alkali metal salt of an imidazoledithiocarboxylic acid compound and an alkylating agent are subjected to a condensation reaction.