JPH07206810A - Bis(carbamoylethyl) trisulfide derivative and its production - Google Patents

Abstract

PURPOSE:To obtain a new bis(carbamoylethyl) trisulfide derivative having the property of reducing agent and useful in the field of pharmaceuticals, dyes, perfumes and waste treatments. CONSTITUTION:This bis(carbamoylethy) trisulfide derivative is a compound of formula I (R1 and R2 each is H or an aliphatic hydrocarbon group), e.g. bis(methylcarbamoylethyl) trisulfide. The compound can be produced by reacting a compound of formula II (R3 is a carboxylic acid ester residue) with a compound of formula HNR1R2. The compound of formula II is easily producible by reacting a 3-mercaptopropionate of formula III with an oxidizing agent in a solvent. The compound of formula I is especially effective for quickly decomposing industrial disinfectants which are resistant to decomposition by activated sludge process in sewage treatment.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel bis (carbamoylethyl) trisulfide derivative and a method for producing the same.

[0002]

2. Description of the Related Art Conventionally, trisulfide group (-SSS-)
The compound having the formula (1) is said to be useful in various fields such as medicines, dyes, and fragrances. For example, in JP-A-60-258157, R ₁ -SSS-R ₂ (wherein R ₁ and R ₂ are ether Group, a carboxyl group, a ketone group, an ester group, a phenyl group, and the like, which represents a cyclic or acyclic alkyl group or alkenyl group having 1 to 12 carbon atoms, are disclosed. In addition, derivatives of bis (carbamoylethyl) trisulfide which are particularly useful as medicines include Chemical Pharmaceutical Bulletin, No. 22
Vol., Pp. 2987-2990 (1974), bis (beta-cyclohexylcarbemoylethyl) trisulfide, bis (beta-chlorophenylcarbamoylethyl) trisulfide, bis (beta-benzylcarbamoylethyl) trisulfide are bioorganic.
Chemistry, Volume 9, pp. 253-260 (1980)
), Bis (2-acetamidoethyl) trisulfide is disclosed.

[0003]

However, all of the above-mentioned bis (carbamoylethyl) trisulfide derivatives contain cyclic compounds such as cycloalkyl and aryl, and are thus used as aliphatic bis (carbamoylethyl) trisulfide derivatives. A compound having a hydrocarbon group has not been obtained yet. Further, these conventional production methods are ones in which a disulfide compound is reacted with an amine and a sulfur compound, or one in which a hydrogen disulfide is reacted with a thiol sulfinate, and in the former, the temperature is high and the reaction time is very long. In addition, the latter has a problem that it is difficult to synthesize hydrosulfide.

[0004]

DISCLOSURE OF THE INVENTION In view of the above problems, the inventors of the present invention have earnestly studied to obtain a compound having an aliphatic hydrocarbon group as a derivative of bis (carbamoylethyl) trisulfide, and as a result, bis (carboxyethyl) ) It was found that a compound having an aliphatic hydrocarbon group can be easily obtained as a derivative of bis (carbamoylethyl) trisulfide by amidating a disulfide body,
The present invention has been completed. That is, the present invention has the general formula

[Chemical 5] (In the formula, R ₁ and R ₂ are the same or different and each represents hydrogen or an aliphatic hydrocarbon group.) as well as,
General formula (II)

[Chemical 6] (Wherein R ₃ represents a carboxylic acid ester residue) and the compound represented by the general formula (III)

[Chemical 7] (Wherein R ₁ and R ₂ are the same or different and each represents hydrogen or an aliphatic hydrocarbon group), and the compound represented by the formula (I) is reacted.

[Chemical 8] (Wherein R ₁ and R ₂ have the same meanings as described above).

In the formula of the compound of the present invention, R ₁ and R ₂ are the same or different and each represents hydrogen or an aliphatic hydrocarbon group.
The aliphatic hydrocarbon group may be a linear or branched alkyl group, which may partially contain an unsaturated bond. Examples of the alkyl group include methyl, ethyl, n-propyl, n-butyl, tert-butyl, iso-butyl, pentyl, hexyl, 2-ethylhexyl, heptyl, octyl, nonyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl and the like. And an alkyl group having 1 to 15 carbon atoms. Examples of the partial unsaturated bond include alkenyl groups such as vinyl, allyl, isopropenyl and methallyl, alkynyl groups such as ethynyl, propynyl and octenyl. Preferred examples of the aliphatic hydrocarbon group, a lower alkyl group having 1 to 4 carbon atoms, and as a preferred embodiment of R _1, R _2, either R ₁ and R _2, the other is hydrogen, carbon atoms 1 to 4 lower alkyl groups can be mentioned. The compound (I) of the present invention has, for example, the general formula (II)

[Chemical 9] (Wherein R ₃ represents a carboxylic acid ester residue) and the compound represented by the general formula (III)

[Chemical 10] (In the formula, R ₁ and R ₂ are the same or different and each represents hydrogen or an aliphatic hydrocarbon group.).

Bis (carboxyethyl) disulfide compounds represented by the general formula (II) have been conventionally used for air oxidation (Heterocycles Vol.9 No.7 (1978)) and hydrogen peroxide oxidation (Journal of Heterocycle). It is known to be synthesized by Click Chemistry 8 (4) 571-580 (1971)) and the like. In addition, for example, the general formula (IV)

[Chemical 11] It can also be easily obtained by reacting 3-mercaptopropionate represented by the formula (R ₃ represents a carboxylic acid ester residue) in a solvent in the presence of an oxidizing agent. The carboxylic acid ester residue represented by R ₃ of the general formula (IV) may be any group as long as it is a group which is not easily eliminated by an oxidation reaction and can be easily eliminated by a subsequent amidation reaction, for example, methyl group. , Ethyl, n-propyl, n-butyl, te
alkyl groups such as rt-butyl, iso-butyl, benzyl, 1-
Phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, methylbenzyl, ethylbenzyl, isopropylbenzyl, t-
Examples thereof include aralkyl groups such as butylbenzyl. Preferred is lower alkyl having 1 to 4 carbon atoms. The reaction solvent is not particularly limited as long as it can dissolve the bis (carboxyethyl) disulfide body (II) and does not inhibit the reaction, and examples thereof include methanol, ethanol and n-propanol. Alcohol, iso-propanol, alcohols such as tert-butanol, acetone, ketones such as methyl ethyl ketone, ethyl ether, ethylene glycol dimethyl ether, dioxane, ethers such as tetrahydrofuran, methylene chloride, chloroform, Alkyl halides such as carbon tetrachloride, polar solvents such as acetonitrile, dimethylformamide, dimethylsulfoxide,
Examples include water. These may be used as a mixture of two or more kinds. Preference is given to using alcohols, particularly preferably methanol.

The oxidizing agent is not particularly limited as long as it has an oxidizing ability and does not inhibit the reaction. For example, halogens such as iodine, bromine and chlorine, for example, first and second Examples thereof include metal ions such as iron ions, copper ions, and cobalt ions, dimethyl sulfoxide, aliphatic dialkyl sulfoxides, and the like. Halogen is preferably used, and iodine is particularly preferably used. The reaction is usually 0 to 70 ° C, preferably 2 to 24 at 20 to 50 ° C.
React for hours. Moreover, it can be performed at room temperature or under pressure. The solvent and the oxidant are each 1 to 30 times by weight relative to 3-mercaptopropionate (IV),
It is used in a range of 0.1 to 10 equivalent times. General formula (II
In the formula (I), R ₁ and R _{2 which} are the same or different and each represent hydrogen or an aliphatic hydrocarbon group have the same meaning as R ₁ and R ₂ described above. Bis (carboxyethyl) disulfide (II)
The reaction between the amine compound (III) and the amine compound (III) is usually 0 to 70.
C., preferably 20 to 50.degree. C. for 1 to 5 hours.
The reaction can be carried out at room temperature or under pressure. Amine compound (III) is bis (carboxyethyl)
The disulfide compound (II) can be used in a range of 0.1 to 10 equivalent times, preferably 1 to 4 equivalent times. Further, it is desirable to carry out the reaction in a solvent, and the above-mentioned bis (carboxyethyl) disulfide body (II) is used as the solvent.
The solvent used for the synthesis of can be used. The amount used is 1 with respect to the bis (carboxyethyl) disulfide body (II).
-30 times by weight, preferably 5 to 10 times by weight. Bis (carbamoylethyl) formed after the reaction
The derivative (I) of trisulfide is a known separation and purification means,
For example, it can be isolated and purified by concentration, concentration under reduced pressure, solvent extraction, crystallization, recrystallization, phase transfer, chromatography and the like. The bis (carbamoylethyl) trisulfide derivative (I) of the present invention produced by such a production method can be obtained in a yield of about 10 to 60%.

[0008]

INDUSTRIAL APPLICABILITY The derivative of bis (carbamoylethyl) trisulfide provided by the present invention has properties as a reducing agent and is usefully used in the fields of medicines, dyes, fragrances, and waste treatment. Industrial disinfectants that are not decomposed by the activated sludge method in the treatment can be quickly decomposed. Further, the production method of the present invention is easier to obtain the raw material, shorter in reaction time, and superior in workability as compared with the conventional production method of the derivative of bis (carbamoylethyl) trisulfide.

[0009]

EXAMPLES The present invention will be specifically described below with reference to reference examples and examples, but the present invention is not limited to these examples. Reference Example 1 (Synthesis of bis (methylcarboxylethyl) disulfide) 2.0 g (17 mmol) of methyl-3-mercaptopropionate was dissolved in 10 ml of methanol and iodine 2.
1 g (17 m atom) was added and reacted at a temperature of 40 ° C. for 12 hours. The obtained reaction solution was concentrated under reduced pressure, ethyl acetate was added, the mixture was washed with 5% aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtered, and the furnace solution was concentrated under reduced pressure and subjected to silica gel column chromatography (acetic acid. After purification with ethyl: n-hexane = 1: 2), oily bis (methylcarboxylethyl) disulfide (3.4 g, yield 86.0%) was obtained.

Example 1 (Synthesis I of bis (methylcarbamoylethyl) trisulfide I) Bis (methylcarboxylethyl) obtained in Reference Example 1
10 ml of disulfide 1.05 g (4.4 mmol)
Of methanol: water = 1: 1 v / v solution of 40% methylamine-methanol solution 2.0 g (25.8 mmo)
1) was added and reacted at 60 ° C. for 2 hours. The obtained reaction solution was concentrated under reduced pressure, chloroform was added, and the mixture was washed with water and saturated saline, dried over anhydrous sodium sulfate, filtered, and the furnace solution was concentrated under reduced pressure. Silica gel column chromatography (MeOH: CHCl3 = 1 : 30) and white crystals of bis (methylcarbamoylethyl) trisulfide (53
0 mg, yield 44.5%) was obtained. Melting point: 115-117 ° C IR (KBr) cm-1: 3303, 2915, 1645, 1560, 1H-N
MR (CDCl3: CD3OD = 1: 1) δ: 2.78 (s, 3H), 3.13 (t, 3)
H, J = 7.1Hz), 2.67 (s, 3H, J = 7.1Hz) MS m / e: 269,237,190 (M ++ 1) Elemental analysis: Calculated value: C: 35.80, H: 6.01, N : 10.4
4, S: 35.84 Actual value: C: 35.74, H: 5.92, N: 10.5
0, S: 35.61

Example 2 ((Synthesis II of bis (methylcarbamoylethyl) trisulfide II) Bis (methylcarboxylethyl) obtained in Reference Example 1
10 ml of disulfide 1.05 g (4.4 mmol)
Was dissolved in a 1: 1 methanol: water solution, and then 2.0 g (25.8 mmol) of a 40% methylamine-methanol solution was added and the mixture was reacted at 20 ° C for 2 hours. The obtained reaction solution was concentrated under reduced pressure, chloroform was added, and the mixture was washed with water and saturated saline,
Anhydrous sodium sulfate was added and dried, and after filtration, the furnace liquid was concentrated under reduced pressure and subjected to silica gel column chromatography (Me
After purification with OH: CHCl3 = 1: 30, white crystals of bis (methylcarbamoylethyl) trisulfide (120 m
g, yield 10.2%) was obtained. Melting point: 115-117 ° C IR (KBr) cm-1: 3305, 2915, 1645, 1561, 1H-NM
R (CDCl3: CD3OD = 1: 1) δ: 2.79 (s, 3H), 3.13 (t, 3H, J = 7.1
Hz), 2.67 (s, 3H, J = 7.1Hz) MS m / e: 269, 237, 190 (M ++ 1)

Claims (3)

[Claims] 1. A general formula: (In the formula, R ₁ and R ₂ are the same or different and each represents hydrogen or an aliphatic hydrocarbon group.) 2. A compound represented by the general formula (II): (Wherein R ₃ represents a carboxylic acid ester residue) and a compound represented by the general formula (III): (Wherein R ₁ and R ₂ are the same or different and each represents hydrogen or an aliphatic hydrocarbon group), and the compound represented by the general formula (I): (In the formula, R ₁ and R ₂ have the same meanings as described above.) A method for producing a compound represented by the formula. 3. The compound according to claim 1, wherein R ₁ and R ₂ are the same or different and each is hydrogen or lower alkyl.