JP2001058977A - Production of ketenimine - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a ketenimine in a high yield under a mild condition without causing the environmental pollution problem by reacting a thioamide compound with a haloiminium salt. SOLUTION: The objective compound of formula III (e.g. N- benzylphenylketenimine) is obtained by desulfhydrating reaction of a compound of formula I (R1 and R2 are each H, an alkyl or an aryl; R3 is an alkyl or an aryl with proviso that the case of R1, R2 and R3 of all an aryl is omitted), e.g. phenylacetic acid thioanilide with a compound of formula II (R4 and R5 are each a lower alkyl; X is a halogen; Y is a counter anion; n is 0 or 1), e.g. 2-chloro-1,3-dimethylimidazolinium chloride. The above reaction is preferably carried out in a reactive solvent (e.g. methylene chloride) in the presence of a base (e.g. triethylamine or the like).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing a ketene imine compound. More specifically, the present invention relates to a method for producing a ketenimine compound from a thioamide compound under mild conditions using a haloiminium salt.

[0002]

2. Description of the Related Art Ketenimine compounds easily react with nucleophiles such as amines and alcohols to give amidines (J. Org. Chem., 30 , 3718 (1965)) and imidoyl esters (J. Am. Chem. Soc., 75 , 657 (1953)) is an important intermediate in organic synthesis because it can be easily converted to compounds. In addition, ketene imine compounds are constructed with heterocycles via cycloaddition reactions (eg, Angew. Chem., 83 ,
171 (1971))
It is also an important synthetic intermediate for pharmaceuticals and pesticides. further,
Ketenimine compounds are used as condensing agents for producing peptides (J. Am. Chem. Soc., 80 , 4069 (195
It is an industrially important compound such as 8)). On the other hand, conventionally used methods for producing ketene imine compounds include a method of synthesizing amides by dehydration with phosphorus pentachloride (J. Org. Chem., 29 , 34 (1964)), and a method of preparing imino chlorides. Synthesis by dehydrochlorination (J. Am. Chem.
Soc., 76 , 4398 (1958)), a method of synthesizing from α-haloamides (J. Am. Chem. Soc., 75 , 657 (1953)), and a method of condensing ketene and phosphorus imine (J. Org). . Che
m., 39 , 3780 (1974)), a method of synthesizing thioamides with mercury salts using hydrogen sulfide (Bull. Chem. Soc.
Jpn., 43 , 1874 (1970)) and the like.

[0003]

However, there have been various problems in the conventionally used method for producing ketene imine compounds. That is, the method of synthesizing amides by dehydration with phosphorus pentachloride requires a high temperature for the reaction, and after the reaction, it is necessary to remove by-product phosphorus compounds. In a method for synthesizing imino chlorides by dehydrochlorination, phosphorus oxychloride generated in a process for producing imino chloride must be removed. Since the method of synthesis from haloamides uses bromine, which is corrosive to metals such as iron, care must be taken when handling. In the method using phosphorus imines, an unstable ketene must be synthesized, and after the reaction is completed, a large amount of triphenylphosphine oxide is by-produced, which must be separated after the reaction. The method using mercury salts has a problem of environmental pollution by heavy metals. Accordingly, it is an object of the present invention to provide a method for industrially producing a ketene imine compound which does not have the above-mentioned drawbacks and does not require complicated operations or special conditions. It is.

[0004]

[Means for Solving the Problems] Under these circumstances, the present inventors have conducted intensive studies on a method for producing a ketene imine compound. As a result, if a thioamide compound is reacted with a haloiminium salt as a hydrogen desulfurizing agent, mild conditions are obtained. The present inventors have found that a ketenimine compound can be obtained under a high yield in a low yield, and based on this finding, have completed the present invention.

That is, the present invention provides the following general formula (1)

Embedded image (In the formula, R ¹ and R ² represent a hydrogen atom, an alkyl group or an aryl group, and R ³ represents an alkyl group or an aryl group, except that all of R ¹ , R ² and R ³ are aryl groups.) In the method for producing a ketene imine compound represented by the following general formula (2):

Embedded image (Wherein R ^{1 to} R ³ have the same meaning as described above) to the thioamide compound represented by the following general formula (3)

Embedded image (Wherein R ⁴ and R ⁵ represent a lower alkyl group, X represents a halogen atom, Y represents a counter anion, and n represents 0 or 1)
A method for producing a ketenimine compound, characterized by reacting a haloiminium salt represented by the formula:

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The above-mentioned general formula (1) showing a ketenimine compound which is a production target compound of the present invention and the above-mentioned general formula (2) showing a thioamide compound which is a starting material thereof
In the above, R ¹ and R ² represent a hydrogen atom, an alkyl group or an aryl group, and R ³ represents an alkyl group or an aryl group, and the alkyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a benzyl group and the like. Examples of the aryl group include a phenyl group, a tolyl group, a xylyl group,
Examples include a naphthyl group and a buphenyl group. These aryl groups may have a substituent such as a halogen atom, an alkoxy group, a nitro group, a dialkylamino group, an acyl group or an alkoxycarbonyl group.

In the present invention, general formula (3) used as a dehydrosulfide agent

Embedded image (Wherein R ⁴ and R ⁵ represent a lower alkyl group, X represents a halogen atom, Y represents a counter anion, and n represents 0 or 1)
In the haloiminium salt represented by R ⁴ and R ⁵
Examples of the lower alkyl group represented by are a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, and the like. Examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among them, a chlorine atom is particularly desirable. The counter anion represented by Y ⁻ is Cl
⁻ , Br ⁻ , I ⁻ , BF ₄ ⁻ , FSO ₃ ^{− and the} like. Among them, Cl ^{− and} BF ₄ ⁻ are particularly desirable. Preferred specific examples of the haloiminium salt (3) include 2-chloro-1,3-dimethylimidazolinium chloride, 2-chloro-1,3-dimethyl-3,4,5,6-tetrahydropyrimidinium chloride. And the like.

In order to carry out the desulfurization reaction in the present invention, the presence of a base is necessary. In this case, the base may be a triethylamine, tripropylamine, tributylamine, dimethylaniline, pyridine, picoline or the like. Tertiary amines are exemplified.

[0009] The desulfurization reaction is preferably carried out in the presence of a reaction solvent. In this case, the reaction solvent may be a reaction of halogenated hydrocarbons, hydrocarbons, ethers, aromatic hydrocarbons, acetonitrile and the like. Solvents that do not participate in the reaction. These solvents may be used alone,
Two or more kinds may be used as a mixture.

The reaction temperature in the above-mentioned method for removing hydrogen sulfide can be carried out at a temperature of about -80 ° C to about 20 ° C. However, if the reaction temperature is too high, the decomposition reaction and side reactions increase. It is preferable to carry out within the range. The reaction time depends on the reaction temperature and cannot be determined unconditionally, but usually 30 minutes to 5 hours is sufficient.

The keteneimine compounds represented by the chemical formulas (a) to (e) were able to be produced by the following examples embodying the hydrogen sulfide reaction of the present invention.

Embedded image

The ketenimine compounds obtained by the method of the present invention are unstable and often difficult to isolate and purify. However, as an impurity, general formula (4)

Embedded image (Wherein R ⁴ and R ⁵ represent a lower alkyl group, and n represents 0 or 1), and a general formula (5)

Embedded image (Wherein R ⁴ and R ⁵ represent a lower alkyl group and n represents 0 or 1), and these compounds contain only a small amount of a cyclic thiourea compound which is inactive in a normal reaction. In a reaction using a ketenimine compound, the ketenimine compound can be used as a raw material without purification.

[0013]

The present invention will be described in more detail with reference to the following examples. The examples of the present invention are typical examples for easy understanding of the reaction. Is not limited to this. In addition, the physical properties of the compounds (a) to (e) produced according to the examples are shown.

Example 1 Phenylacetic acid thioanilide 1 in 10 ml of methylene chloride
of 2-chloro-1,3-dimethylimidazolinium chloride in 5 ml of methylene chloride in an ice bath.
ol was slowly added dropwise. After the addition was completed, 4 mmol of triethylamine was added, and the mixture was stirred in an ice bath for 3 hours. The solvent was distilled off under reduced pressure, and hexane was added.
After cooling to 0 ° C., the solid was filtered off. Hexane was distilled off under reduced pressure to obtain ketenimine of the above compound (a) in a yield of 94%. Its ¹ H-NMR spectrum and IR spectrum are as follows. Since the compound (a) produced here is not a stable compound that can be isolated and purified, the yield was determined by NMR. ¹ H-NMR (δ, CDCl ₃ ) 5.26 (s, 1H), 7.09-7.39 (m, 1
0H). IR (ν _max , KBr) 2016 cm ⁻¹ .

Example 2 The same procedure as in Example 1 was carried out except that thiop-toluide phenylacetate was used instead of thioanilide phenylacetate. Of this one
^{The 1} H-NMR spectrum and IR spectrum are as follows. Since the compound (b) produced here is not a stable compound that can be isolated and purified, the yield was determined by NMR. ¹ H-NMR (δ, CDCl ₃ ) 2.36 (s, 3H), 5.23 (s, 1H),
7.07-7.29 (m, 9H). IR (ν _max , KBr) 2004 cm ⁻¹ .

Example 3 The same procedure as in Example 1 was carried out except that phenylacetic acid thio (p-methoxy) anilide was used in place of phenylacetic acid thioanilide to obtain the ketenimine of the compound (c) in a yield of 78%. Its ¹ H-NMR spectrum and IR spectrum are as follows. The compound (c) produced here is isolated and
Since the compound is not stable enough to be purified, the yield is N
Determined by MR. ¹ H-NMR (δ, CDCl ₃ ) 3.82 (s, 3H), 5.22 (s, 1H),
6.87 (d, 2H, J = 9.1Hz), 7.10-7.18 (m, 3H), 7.24-7.3
2 (m, 4H). IR (ν _max , KBr) 2004 cm ⁻¹ .

Example 4 Ketenimine of the above compound (d) was obtained in a yield of 86% using N-benzyldiphenylacetic acid thioamide in place of phenylacetic acid thioanilide in Example 1. Its ¹ H-NMR spectrum and IR spectrum are as follows. Since the compound (d) produced here is not stable enough to be isolated and purified, the yield is NM
Determined by R. ¹ H-NMR (δ, CDCl ₃ ) 4.77 (s, 2H), 7.14-7.35 (m, 1
5H). IR (ν _max , KBr) 2012 cm ⁻¹ .

Example 5 In Example 1, N-benzylphenylacetic acid thioamide was used in place of phenylacetic acid thioanilide to obtain the ketenimine of the compound (e) and the N-benzylphenylketenimine in a yield of 82%. . Its ¹ H-NMR spectrum and IR spectrum are as follows. Since the compound (e) produced here is not a stable compound that can be isolated and purified, the yield was determined by NMR. ¹ H-NMR (δ, CDCl ₃ ) 4.17 (d, 2H, J = 2.2 Hz), 4.82
(t, 1H, J = 2.2 Hz), 7.02-7.07 (m, 2H), 7.19-7.36
(m, 8H). IR (ν _max , KBr) 2022 cm ⁻¹ .

[0019]

According to the production method of the present invention, ketenimines can be industrially and efficiently produced from thioamides under mild conditions. In addition, since no heavy metal is used, there is an advantage that there is no problem of environmental pollution.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Yasuo Kama 1-1 Higashi 1-1, Tsukuba, Ibaraki Pref. F-term (Reference) 4H006 AA02 AC59 BD20

Claims (1)

[Claims] (1) The following general formula (1): (In the formula, R ¹ and R ² represent a hydrogen atom, an alkyl group or an aryl group, and R ³ represents an alkyl group or an aryl group, except that all of R ¹ , R ² and R ³ are aryl groups.) In a method for producing a ketene imine compound represented by the following general formula (2): (Wherein R ^{1 to} R ³ have the same meaning as described above) by converting the thioamide compound represented by the following general formula (3) (Wherein R ⁴ and R ⁵ represent a lower alkyl group, X represents a halogen atom, Y represents a counter anion, and n represents 0 or 1)
A method for producing a ketenimine compound, comprising subjecting a haloiminium salt represented by the formula to a hydrogen sulfide reaction.