JPH04297452A - Production of thiocyanic acid esters - Google Patents

Abstract

PURPOSE:To simply obtain isothiocyanic acid esters in high yield by thermally isomerizing thiocyanic acid esters in the presence of a specific catalyst. CONSTITUTION:A compound expressed by the formula R-SCN (R is 1-18C alkyl, aralkyl, cycloalkyl, alkenyl, alkynyl or hetero ring) at 20-250 deg.C, preferably 50-170 deg.C in the presence of a catalyst consisting of a compound (e.g. tetraethylammonium bromide) expressed by formula I (R1 to R3 are lower alkyl; R4 is lower alkyl or aralkyl; X is halogen) or a compound (e.g. tetraethylphosphonium bromide) expressed by formula II to provide isothiocyanic acid esters expressed by the formula R-NCS.

Description

[Detailed description of the invention]

0001

[Industrial Application Field] The present invention relates to a method for producing isothiocyanate esters, and more particularly, isothiocyanate esters useful as raw materials for the synthesis of various chemical products, including medicines and agrochemicals, can be obtained easily and in high yield. This provides a new manufacturing method.

0002

BACKGROUND OF THE INVENTION There have been several reports on methods for synthesizing isothiocyanate esters. For example, (1) a method of decomposing dithiocarbamates in the presence of heavy metal salts (
Ber. 1, 170 (1868), Org. Sy
nth. , I, 447 (1941)) RNH-C(=S)-SNa +Pb(NO3)2
+NaOH→[RSCN]→RNCS+PbS +2N
aNO3...(Formula 1) (2) Method of reacting dithiocarbamate and chloroformate (Org.Synth
．． , III, 599 (1955)) RNH-C (
=S)-SNa +Cl-C(=O)-OC2H5→R
NCS+Nacl+C2H5OH+COS......(Formula 2) (3) Method of reacting primary amine and thiophosgene (Acta.Chem.Scand., 11 129
8 (1957), J. Am. Chem. Soc. 54
, 781 (1962)) R-NH2 +CSCl2 →RNCS+2HCl
………………………………………………(Formula 3) (4)
Method for reacting dithiocarbamic acid and cyanamide (JP-A-56-172371) RNH-C(=S)-SH+NH2CN →RNC
S+(NH2)2CS……………………………………(Formula 4) However, in these methods, in (1),
Since heavy metal salts are used, it is not advantageous from an economic point of view, as it requires reliable treatment to recover metals from waste liquid and prevent pollution. In (2), chloroformate is relatively expensive, and the COS produced by the reaction with it is
is toxic and requires safety precautions;
Method 3) has drawbacks such as the use of expensive and highly toxic thiophosgene. In (4), cyanamide is hygroscopic and therefore difficult to handle, and is difficult to obtain as a high-grade industrial raw material.

On the other hand, the following method (5) is known in which a halogen compound and a metal thiocyanate are heated and isomerized to obtain an isothiocyanate ester. This method is commonly used. (5) Method using thiocyanate metal salt and halogen compound (J. Am. Chem. Soc. 59, 201
2 (1937), JP-A-1-172371, JP-A-2-
221255) NaSCN (or KSCN) +RX→RNCS+
NaX (or KX) …………………………………(Formula 5)
Among these methods for producing isothiocyanate esters, the method of producing isothiocyanate esters by thermal isomerization of thiocyanate esters is the simplest method, but a six-membered ring intermediate structure such as allyl thiocyanate is possible. In some cases, high yields can be obtained under mild conditions, but in general high-temperature reactions are required, the isomerization rate is slow, and the isothiocyanate ester once formed is thermally degraded, resulting in lower yields. There are low drawbacks. The key to improvement is how to speed up the isomerization and how to increase the reaction rate, but preferred conditions have not been achieved with conventional methods. For example, JP-A-2-2212
In 55, as a method for producing alkenyl isothiocyanate, 5-bromo-1-pentene and sodium thiocyanate are reacted, and the obtained 4-pentenyl thiocyanate is reacted with a base or an alkali metal iodide in an aprotic polar solvent. A method of producing 4-pentenyl isothiocyanate by adding and thermally isomerizing is known. However, this method requires a large amount of alkali metal, such as potassium iodide, and has economical problems such as a low total yield of 12 to 24%, so it cannot be said to be an industrially advantageous method. It's tough.

0004

[Problems to be Solved by the Invention] In view of the above circumstances, the present inventors have conducted intensive research on the thermal isomerization reaction of thiocyanate esters in order to solve the problems of the conventional technology. Discovered a simple, high-yield, and industrially advantageous method for producing isothiocyanate esters,
The present invention has now been completed.

[0005]

[Means for Solving the Problems] That is, the present invention provides a general formula [1] R-SCN [1] (wherein R is an alkyl group in the range of C1 to C18, an aralkyl group, a cycloalkyl group, an alkenyl group) group, alkynyl group, and a heterocycle) as a catalyst, the general formula [2] R2-N+ (R1)(R3)-R4X- [2] (in the formula, R1, R2, R3 represents a lower alkyl group, R4 represents a lower alkyl group or an aralkyl group, and X represents a halogen atom),
Or, general formula [3] R2-P+ (R1)(R3)-R4X- [3] (wherein, R1, R2, R3 represent a lower alkyl group, R4 represents a lower alkyl group, an aralkyl group, and X is [4] R-NCS [4] (wherein R is the same as the above-mentioned group) The gist of this paper is a method for producing isothiocyanate esters. To explain the aspect of the present invention in more detail, the basic reaction to obtain the isothiocyanate ester is represented by (Formula 6). That is, (wherein R represents an alkyl group, an aralkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, and a heterocycle in the range of C1 to C18), and the general formula [1
The thiocyanate ester represented by ] can be obtained by a reaction between a corresponding halogen compound and a thiocyanate (J. Amer.
Chem. Soc. , 57 198 (1935), JP-A-61-143353, JP-A-2-221255), the thiocyanate ester obtained therein can be produced in a high yield in the presence of a solvent or in the absence of a solvent. ,
The isothiocyanate esters represented by the general formula [4] can be obtained in high yield by thermal isomerization under predetermined conditions in the presence of the catalysts represented by the general formulas [2] and [3]. . That is, among the R represented by the general formula [1], general formula [4], and (formula 6), the alkyl group is
For example, methyl group, ethyl group, propyl group, butyl group,
Examples include pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, lauryl group, hexadecyl group, stearyl group, etc. Substituted alkyl groups include, for example, 2-methoxyethyl group, chloroethyl group, bromoethyl group. , 3-triethoxysilylpropyl group, 6-methylthiohexyl group, and the like. Examples of the aralkyl group include a benzyl group, a benzyl group in which a benzene ring is substituted with a chloro, methoxy group, or a nitro group, and a phenethyl group. Examples of the cycloalkyl group include:
Examples include cyclobutyl group, cyclopentyl group, cyclohexyl group, and cycloheptyl group. Examples of the alkenyl group include allyl group, butenyl group, pentenyl group, and hexenyl group, and examples of the alkynyl group include propargyl group and butynyl group. Heterocycles may include saturated or unsaturated rings containing O, S and N atoms. Furthermore, R1 represented by the general formula [2] and general formula [3],
Among R2 and R3, the alkyl group is, for example,
Examples of R4 include a methyl group, an ethyl group, a propyl group, a butyl group, and examples of the alkyl group include a methyl group, an ethyl group, a propyl group, a butyl group, and examples of the aralkyl group include a benzyl group, Examples include phenethyl group. Examples of the halogen atom include chlorine, bromine, and iodine.

[0006] In carrying out the thermal isomerization in the present invention, no solvent may be used, and when a solvent is used, the amount is 0.05 mol or more, preferably 0.05 mol or more, based on the compound represented by the general formula [1]. 1 to 1.0 mol is used. The solvent used in the present invention may be any solvent as long as it can dissolve and react the compounds represented by the general formulas [1], [2], and [3], such as methanol and ethanol. Alcoholic solvents, esters such as methyl acetate and ethyl acetate, ethers such as ethyl ether, tetrahydrofuran and dioxane, acetonitrile, dimethylformamide, dimethyl sulfoxide, dimethylacetamide, N-methylpyrrolidone, sulfolane, 1.
Although aprotic polar solvents such as 3-dimethyl-2-imidazolidinone can be used, aprotic polar solvents with a high boiling point are particularly preferred. The temperature useful for the reaction of the present invention can be appropriately selected so as to obtain the best production rate of isothiocyanate ester, and is 20°C to 25°C.
A temperature of 0°C, preferably 50 to 170°C is suitable.

As described above, the purpose of the present invention is to provide an industrially advantageous method for producing isothiocyanate esters, and the most preferred embodiment is to prepare a thiocyanate ester represented by the general formula [1] with a suitable aprotic polarity. In a solvent, general formula [2
] Quaternary ammonium salt or general [3]
The isothiocyanic acid ester represented by the general formula [4] is obtained in high yield by thermal isomerization in a short time in the presence of a catalyst such as a phosphonium salt represented by the formula [4]. Next, Table 1 shows examples of the substantial effects of the catalyst according to the present invention.

[0008]

[Table 1]

When a quaternary ammonium salt or phosphonium salt is used as an isomerization catalyst, the effect of promoting the reaction is remarkable, compared to when a conventional catalyst is used under the same conditions.
It became possible to significantly shorten the reaction time, suppress thermal deterioration of the product by shortening the heating time, and obtain the desired product in high yield and quality.

0010

Effects of the Invention Among the various methods for producing isothiocyanate esters, the method of producing isothiocyanate esters by thermal isomerization of thiocyanate esters is the simplest method. Unless intermediate structures are possible, conventionally known cases often require rather harsh reaction conditions, and the isomerization rate is slow, resulting in secondary product formation due to prolonged heating. It was difficult to obtain a high yield due to deterioration, which was a major problem. On the other hand, the method of the present invention uses the general formula [
The isothiocyanate ester represented by formula [4] is isomerized by heating in an aprotic polar solvent in the presence of a quaternary ammonium salt or a phosphonium salt, and the isothiocyanate ester represented by general formula [4] can be easily and highly This is an innovative manufacturing method with high yield and economic efficiency.

[0011]

[Examples] Examples are shown below to explain the present invention in more detail, but these examples are not intended to limit the present invention. [Example 1. ] Synthesis of n-propyl isothiocyanate (compound No. 1) 40.6 g of n-propyl thiocyanate and 8.4 g of tetraethylammonium bromide were mixed with 1,3-dimethyl-
After dissolving in 75 ml of 2-imidazolidinone, 140-1
Stirred at 45°C for 2 hours. After the reaction is complete, add ethyl acetate 2
After extraction with 50 ml of water, aqueous solution and drying over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure, and the resulting oil was distilled to obtain compound No. 1 with a boiling point of 151-152°C. 1 37
．． 9 g (yield 75%) was obtained.

[Example 2. ]isothiocyanic acid sec
-Synthesis of Butyl (Compound No. 2) 66.4 g of sec-butyl thiocyanate and 8.5 g of tetraethylphosphonium bromide were combined with N-methyl-2
- After dissolving in 110ml of pyrrolidone, 140-145
Stirred at ℃ for 3 hours. After the reaction is complete, ethyl acetate 380
ml, washed with water, dried over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure, and the resulting oil was distilled.
Compound No. 1 with a boiling point of 159-160°C. 2 57.0
g (yield 82%) was obtained.

[Example 3. ] Synthesis of 5-hexenyl isothiocyanate (compound No. 6) After dissolving 34.0 g of 5-hexenyl thiocyanate and 6.4 g of tetrabutylammonium bromide in 50 ml of 1,3-dimethyl-2-imidazolidinone, 140 ~
The mixture was stirred at 145°C for 2 hours. After the reaction was completed, it was extracted with 150 ml of ethyl acetate, washed with water, dried over anhydrous magnesium sulfate, and the ethyl acetate was distilled off under reduced pressure. 6
27.0 g (yield 75%) was obtained.

[Example 4. ] Synthesis of 2-methoxyethyl isothiocyanate (compound No. 9) 50.0 g of 2-methoxyethyl thiocyanate and 9.7 g of tetraethylphosphonium bromide were mixed with sulfolane 6.
After dissolving in 0ml, it was stirred at 140-145°C for 2 hours. After the reaction was completed, it was extracted with 180 ml of ethyl acetate, washed with water, dried over anhydrous magnesium sulfate, and the ethyl acetate was distilled off under reduced pressure.
C/23 mmHg Compound No. 9 40.0 g (yield 80%) was obtained.

[Example 5. ] Synthesis of benzyl isothiocyanate (compound No. 11) 45.6 g of benzyl thiocyanate and 6.4 g of tetraethylammonium iodide were dissolved in 64 ml of N,N,-dimethylacetamide and stirred at 140 to 145°C for 1.5 hours. . After the reaction is complete, add 210 ethyl acetate
ml, washed with water, dried over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure, and the resulting oil was distilled.
Compound N with a boiling point of 105-106 °C/10 mmHg
o. 37.4 g (yield 74%) of 11 was obtained.

[Comparative Example] Synthesis of 5-hexenyl isothiocyanate (Compound No. 6) 34.0 g of 5-hexenyl thiocyanate and 20.0 g of potassium iodide were dissolved in 50 ml of 1,3-dimethyl-2-imidazolidinone. Afterwards, the mixture was stirred at 140-145°C for 2 hours. After the reaction was completed, it was extracted with 150 ml of ethyl acetate, washed with water, dried over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure, and the resulting oil was distilled.
Compound No. 2°C/7mmHg. 6 12.9g (yield 36%) was obtained. Table 2 shows various isothiocyanate esters synthesized by the method of the present invention.

[0017]

[Table 2]

Claims (1)

[Claims] Claim 1: General formula [1] R-SCN [1] (wherein R represents an alkyl group, an aralkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, or a heterocycle in the range of C1 to C18. ) Using a thiocyanate ester as a catalyst, the general formula [2] R2-N+ (R1)(R3)-R4X- [2] (wherein, R1, R2, R3 are lower alkyl groups, and R4 is a lower alkyl group) , represents an aralkyl group, and X represents a halogen atom),
Or, general formula [3] R2-P+ (R1)(R3)-R4X- [3] (wherein, R1, R2, R3 represent a lower alkyl group, R4 represents a lower alkyl group, an aralkyl group, and X is [4] R-NCS [4] (wherein R is the same as the above-mentioned group) A method for producing isothiocyanate esters.