JPH0558608B2 - - Google Patents

Description

[Detailed description of the invention]

(Field of Industrial Application) The present invention provides a novel method for producing amide compounds useful as medicines and agricultural chemicals, or raw materials and intermediates thereof. (Prior Art and Problems to be Solved by the Invention) The present inventors have been conducting research on the synthesis of N-substituted amide compounds using Schiff's base compounds as raw materials and their physiological activities. For example, the present inventors published the general formula in Japanese Patent Application Laid-Open No. 60-4148, (However, E is a halogen atom, an alkoxy group, or an alkylthio group, and G ₁ , G _{2 ,} and G ₃ are the same or different hydrogen atoms, halogen atoms, alkyl groups, alkoxy groups, or alkylthio groups, respectively.) It was proposed that the N-substituted chloroacetanilide represented by is extremely useful as a herbicide. The N-substituted chloroacetanilide is generally synthesized using a Schiff base compound as a raw material through a reduction step and a chloroacetylation step as shown in the following formula. That is, if Schiff's base is used as a raw material, a two-step reaction must be carried out to reach the desired product, and in some cases, expensive and difficult-to-handle compounds such as lithium aluminum hydride must be used for reduction. Industrial technical issues remained. (Means and Effects for Solving the Problems) The present inventors have conducted intensive research on the method for synthesizing the above-mentioned amide compound. As a result, they surprisingly discovered that an amide compound can be easily synthesized in one step by reacting a Schiff base compound, a silane compound, and a carboxylic acid derivative, leading to the completion of the present invention. That is, the present invention provides (a) general formula () (In the formula, R ₁ represents a substituted or unsubstituted aryl group or a substituted or unsubstituted heteroaryl group, and R ₂ and R ₃ are the same or different hydrogen atoms or carbon atoms of 1 to 6 represents an alkyl group, R ₂ and R ₃ may be interconnected to form a cyclic alkylene group, and R ₄ is a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 8 carbon atoms; represents a group, or a substituted or unsubstituted aryl group,
R ₅ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, A represents an oxygen atom or a sulfur atom, and n represents 0 or 1. However, when R ₅ is a hydrogen atom, n is 0. ) A Schiff base compound represented by (b) a silane compound represented by the general formula ( ) HSiXYZ (wherein X, Y, and Z are the same or different hydrogen atoms or halogen atoms), and (c) General formula () R ₆ COM (wherein R ₆ is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group, M is a halogen atom or

[Formula] is a group. ), characterized in that it is reacted with a carboxylic acid derivative represented by the general formula () (In the formula, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , A and n
is the same as above. ) The present invention relates to a method for producing an amide compound represented by The Schiff base represented by the general formula () used as one of the raw materials of the present invention is a novel compound synthesized for the first time by the present inventors. In the general formula (), R ₁ is substituted. or an unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group. Examples of unsubstituted aryl groups include phenyl group, naphthyl group, anthranyl group,
and a phenanthrenyl group are preferred. In addition, examples of the unsubstituted heteroaryl group include a heteroaryl group containing an oxygen atom, a sulfur atom, and a nitrogen atom;
For example, furyl group, thienyl group, pyrrolyl group, benzofuryl group, benzothienyl group, pyrazolyl group,
An imidazolyl group, a thiazolyl group, etc. are suitable. Further, the above aryl group and heteroaryl group may be substituted, and the substituent is not particularly limited, and any known substitutable group may be employed. Specific examples are as follows. That is, an alkyl group having 1 to 6 carbon atoms; a halogen atom such as a chlorine atom, a bromine atom, an iodine atom, and a fluorine atom; an alkoxy group having 1 to 6 carbon atoms; a haloalkyl group having 1 to 6 carbon atoms; 1-6 alkylthio group; 1 carbon atom
an alkyl group and/or a chlorine atom consisting of ~6,
A phenoxy group substituted or unsubstituted with a halogen atom selected from the group consisting of a bromine atom, an iodine atom, and a fluorine atom; an alkyl group consisting of 1 to 6 carbon atoms and/or a chlorine atom, a bromine atom,
These include phenyl groups substituted or unsubstituted with halogen atoms selected from the group consisting of iodine atoms and fluorine atoms. More specific examples of the most preferred substituted aryl groups and heteroaryl groups are as follows. That is, substituted aryl groups include alkylphenyl groups such as methylphenyl, dimethylphenyl, ethylphenyl, diethyl phenyl, propylphenyl, butylphenyl, pentylphenyl, methylethylphenyl, and methylpropylphenyl; fluorophenyl, difluorophenyl; Halophenyl groups such as enyl, chlorophenyl, dichlorophenyl, trichlorophenyl, bromophenyl, and iodophenyl; alkoxyphenyl groups such as methoxyphenyl, dimethoxyphenyl, ethoxyphenyl, propoxyphenyl, and butoxyphenyl; (chloromethyl) phenyl,
(Haloalkyl)phenyl groups such as (chloroethyl)phenyl, (chloropropyl)phenyl, (bromoethyl)phenyl, (fluoroethyl)phenyl, and (trifluoromethyl)phenyl; methylthiophenyl, ethylthiophenyl, and propylthiophenyl Alkylthiophenyl groups such as enyl; phenoxyphenyl, (methylphenoxy)phenyl, (ethylphenoxy)phenyl, (chlorophenoxy)phenyl, (bromophenoxy)phenyl, (fluorophenoxy)phenyl, and [chloro(methyl)phenoxy] ] Phenoxyphenyl group such as phenyl; (methylphenyl) phenyl,
Phenylphenyl groups such as (ethylphenyl)phenyl, (propylphenyl)phenyl, (chlorophenyl)phenyl, and (fluorophenyl)phenyl; chloro(methyl)phenyl, chloro(ethoxy)phenyl, and methyl(methoxy)
Substituted phenyl groups such as phenyl; methylnaphthyl,
Dimethylnaphthyl, ethylnaphthyl, chloronaphthyl, bromonaphthyl, dichloronaphthyl, methoxynaphthyl, (trifluoromethyl)naphthyl,
Examples include substituted aryl groups such as methylthionaphthyl, phenoxynaphthyl, phenylnaphthyl, methylanthranyl, chloroanthranyl, methoxyanthranyl, and methylphenanthryl. Substituted heteroaryl groups include methylfuryl, dimethylfuryl, ethylfuryl, propylphylfuryl, chlorofuryl, bromofuryl, methoxyfuryl, ethoxyfuryl, propoxyfuryl,
Substituted furyls such as (trifluoromethyl)furyl, methylthiofuryl, ethylthiofuryl, phenoxyfuryl, and phenylfuryl; methylthienyl, dimethylthienyl, ethylthienyl, propylthienyl, butylthienyl, fluorothienyl, chlorothienyl, bromothienyl, methoxythienyl, Substituted thienyl groups such as ethoxythienyl, propoxythienyl, (chloroethyl)thienyl, (trifluoromethyl)thienyl, methylthiothienyl, ethylthiothienyl, dibromothienyl, dimethoxythienyl, phenoxythienyl, and phenylthienyl; N-methylpyrrolyl, N
-ethylpyrrolyl, methyl-N-methylpyrrolyl, chloro-N-ethylpyrrolyl, methoxy-N
- Substituted pyrrolyl groups such as methylpyrrolyl, methylthio-N-methylpyrrolyl, and phenoxy-N-methylpyrrolyl; substituted benzofuryls such as methylbenzofuryl, chlorobenzofuryl, ethoxybenzofuryl, (trifluoromethyl)benzofuryl, and phenoxybenzofuryl Groups; Substituted benzothienyl groups such as ethylbenzothienyl, fluorobenzothienyl, methoxybenzothienyl, and phenylbenzothienyl; methylpyrazolyl group, dimethylpyrazolyl group, phenylpyrazolyl group, methoxyimidazolyl group, phenylimidazolyl group, and methylthiazolyl group Examples include groups. R ₂ and R ₃ in the general formula () are the same or different hydrogen atoms or alkyl groups having 1 to 6 carbon atoms, and R ₂ and R ₃ are interconnected to form a cyclic alkylene group. may be formed. The alkyl group may be a linear or branched alkyl group, and specific examples include a methyl group, an ethyl group,
n-propyl group, iso-propyl group, n-butyl group, iso-butyl group, n-pentyl group, and n-
Hexyl group, etc. Further, when R ₂ and R ₃ are interconnected to form a cyclic alkylene group, the alkylene group is an ethylene group, trimethylene group, tetramethylene group, pentamethylene group, hexamethylene group, heptamethylene group. , and octamethylene groups are preferred. R ₄ shown in the above general formula () is a hydrogen atom,
It is a substituted or unsubstituted alkyl group having 1 to 8 carbon atoms, or a substituted or unsubstituted aryl group. The unsubstituted alkyl group is
Those specifically exemplified as R ₂ and R ₃ are preferable,
In addition to these, for example, alkyl groups having 7.8 carbon atoms such as heptyl group and octyl group are suitable. Further, the alkyl group may be substituted, and the substituents are not particularly limited, but the following are examples of generally industrially preferred ones. That is, an alkoxy group having 1 to 6 carbon atoms; an alkylthio group having 1 to 6 carbon atoms; an alkylcarbonyl group having 1 to 6 carbon atoms; an alkyl group having 1 to 6 carbon atoms; an alkoxy group, or a halogen atom-substituted or unsubstituted phenoxy group;
Alkyl group having 1 to 6 carbon atoms, 1 to 6 carbon atoms
6 alkoxy group, or a halogen atom-substituted or unsubstituted phenyl group. Specific examples of suitable substituted alkyl groups are as follows. For example, alkoxyalkyl groups such as methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxybutyl, butoxyethyl, butoxypropyl, and pentoxyethyl; methylthiomethyl , methylthioethyl,
Alkylthioalkyl groups such as methylthiopropyl, methylthiobutyl, methylthiopentyl, ethylthioethyl, propylthiomethyl, propylthiopropyl, and butylthiomethyl; methylcarbonylmethyl, methylcarbonylethyl, methylcarbonylpropyl, methylcarbonylbutyl,
Alkylcarbonylalkyl groups such as methylcarbonylpentyl, methylcarbonylhexyl, ethylcarbonylethyl, ethylcarbonylpropyl, ethylcarbonylhexyl, propylcarbonylmethyl, propylcarbonylpropyl, butylcarbonylethyl, pentylcarbonylpropyl, and hexylcarbonylbutyl; phenoxymethyl, phenoxyethyl , phenoxypropyl,
Phenoxybutyl, (methylphenoxy)ethyl,
(ethylphenoxy)methyl, (propylphenoxy)ethyl, (methoxyphenoxy)propyl,
(ethoxyphenoxy)butyl, (propoxyphenoxy)ethyl, (chlorophenoxy)methyl,
Phenoxyalkyl groups such as (bromophenoxy)ethyl, (fluorophenoxy)propyl, and [(chloro)methylphenoxy]ethyl; phenylmethyl, phenylethyl, phenylpropyl,
Phenylalkyls such as (methylphenyl)ethyl, (ethylphenyl)propyl, (propylphenyl)methyl, (methoxyphenyl)methyl, (methoxyphenyl)propyl, (ethoxyphenyl)ethyl, and (propoxyphenyl)ethyl. Examples include groups. The substituted or unsubstituted aryl group in R ₄ is preferably the same as the substituted or unsubstituted aryl group exemplified in R ₁ above. R ₅ in the general formula () is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. The alkyl group is preferably the same as the alkyl group for R ₂ and R ₅ above. In the general formula (), A is an oxygen atom or a sulfur atom. Moreover, n is 0 or. However, _R5
When is a hydrogen atom, n is 0. In many cases, various positional isomers exist in the compounds having the groups specifically exemplified above, but they can be used in the present invention without being particularly limited. The structure of the compound represented by the general formula () of the present invention can be confirmed by the following means. (b) By measuring the infrared absorption spectrum (IR), it is possible to observe absorption based on CH bonds in the vicinity of 3050 cm ^-1 to 2800 cm ^-1 and strong absorption based on C=H- bonds in the vicinity of 1630 cm ^-1 . I can do it. (b) By measuring the mass spectrum (mS) and calculating the composition formula corresponding to each peak observed (generally the mass number expressed as m/e, which is the ion molecular weight m divided by the ion mass number e). It is possible to know the molecular weight of the compound subjected to measurement and the bonding mode of each atomic group within the molecule. In other words, the sample subjected to measurement is expressed by the general formula When expressed as , a molecular ion peak (hereinafter abbreviated as M) is generally observed, and the molecular weight of the compound subjected to measurement can be determined. Further, for the compound of the present invention represented by the above general formula, characteristic peaks corresponding to M - (A) _o --R ₅ etc. are observed, and the bonding mode within the molecule can be known. (c) By measuring ¹ H-nuclear magnetic resonance spectrum ( ¹ H-nmr), it is possible to know the bonding state of hydrogen atoms present in the compound of the present invention represented by the above general formula. Compound ¹ H-nmr (δ, ppm: based on tetramethylsilane, representative example of deuterated chloroform solvent) of the compound represented by the general formula () The analysis results of the following compound are as follows. That is, a triplet of 3 protons based on the methyl group (f) at 1.28ppm, a doublet of 6 protons based on the methyl group (c) at 1.78ppm, and a doublet of 6 protons based on the methyl group (a) at 2.30ppm. Single line of 3 protons,
Quadruple line of two protons based on methylene group (e) at 4.20ppm, benzene ring at 6.80ppm to 7.33ppm
(b) and a multiplet of five protons based on methine group (d) were observed. (d) Determine the weight percentages of carbon, hydrogen, nitrogen, and halogen (and sulfur if sulfur is included) by elemental analysis, and further subtract the sum of the weight percentages of each recognized element from 100. The weight percent of oxygen can be calculated, and therefore the compositional formula of the compound can be determined. The Schiff base compound of the present invention has the general formula:
Although the properties vary somewhat depending on the types of R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , A, and n and the degree of purification, they are generally colorless to yellow liquids or solids at room temperature and normal pressure. . The compound of the present invention is soluble in common organic solvents such as benzene, ether, alcohol, chloroform, acetonitrile, dimethylformamide, and dimethyl sulfoxide, but is sparingly soluble in water. The method for producing the compound represented by the general formula () of the present invention is not particularly limited. A typical manufacturing method is described below. general formula [In the formula, R ₁ , R ₂ , and R ₃ are the same as above,
J is a hydrogen atom or a (trialkyl)silyl group. ] The imine compound represented by and the general formula (In the formula, R ₄ , R ₅ , A, and n are the same as above, and Y and Z are a hydrogen atom or an alkyl group.
However, if n is 0,

[Formula] part is

[Formula] may also be used. ) The compound represented by the general formula () can be obtained by reacting with the compound represented by the above general formula (). The imine compound represented by the general formula () used as a raw material for this method may be obtained by any method. The general formula is formed by the reaction of a nitrile compound and an organomagnesium compound or an organolithium compound as shown in the following formula. It is obtained by treating the intermediate with a proton donor or (trialkyl)silyl compound. (In the formula, R ₁ , R ₂ , R ₃ , and J are the same as above, and Q is Li, MgCl, MgBr, or MgI.) The molar ratio of both compounds charged in the reaction is determined as necessary. Although it may be determined, it is common to use equimolar amounts or a slight excess of the compound of general formula (). Moreover, the order of addition of both compounds is not particularly limited. The reaction can be carried out in an organic solvent or without a solvent. When using an organic solvent, suitable examples include benzene, toluene, xylene,
Hexane, chloroform, methylene chloride, ethyl ether, dioxane, tetrahydrofuran, acetone, methyl ethyl ketone, acetonitrile,
Examples include ethyl acetate, N,N-dimethylformamide, hexamethylphosphoramide, and dimethyl oxide. The reaction temperature in the above reaction can be selected from a wide range, generally -50°C to 200°C, preferably -30°C.
It may be selected within the range of ℃ to 150℃. The reaction time varies depending on the raw materials and reaction temperature, but is usually 5 minutes to
The duration may be selected from 10 days, preferably from 30 minutes to 2 days. Further, it is preferable to stir the reaction mixture during the reaction. In addition, in order to promote the reaction, an acid such as hydrochloric acid, acetic acid, p-toluenesulfonic acid, etc.
Lewis acids such as _BF3・_Et2O , aluminum chloride,
Means of adding calcium hydride, molecular sieves, silica gel, alumina, etc. are often suitably used. desired product. That is, the method for isolating and purifying the Schiff base compound represented by the general formula () is not particularly limited, and any known method can be employed. For example, after performing the above reaction, reacting with a (trialkyl)silyl compound or reacting with a proton donor, distilling off the reaction solvent from the reaction solution, and then vacuum distilling the residue to obtain the desired product. be able to. Furthermore, when the reaction is carried out without a solvent, the desired product can be obtained by vacuum distilling the reaction solution. Furthermore, purification by chromatography or, if the product is a solid, production by recrystallization, etc., can also be employed. In addition, specific examples of the above proton donor include:
Specific examples of (trialkyl)silyl compounds such as water and acetic acid include trimethylsilyl chloride and triethylsilyl bromide. Another raw material of the present invention is a silane compound represented by the general formula (), that is, HSiXYZ.
In the general formula (), X, Y and Z may be the same or different hydrogen atoms or halogen atoms without particular limitation. As the halogen atom, each atom of chlorine, bromine, iodine or fluorine can be used without particular limitation, but chlorine atom and bromine atom are particularly preferred. Specific examples of the above-mentioned silane compounds that are particularly preferably used industrially include HSiCl ₃ ,
These are compounds such as HSiBr ₃ , H ₂ SiCl ₂ , H ₂ SiBr ₂ and H ₃ SiBr. Another raw material of the present invention is a carboxylic acid derivative represented by the general formula (), that is, R ₆ COM. R ₆ in the carboxylic acid derivative is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted allary group, or a substituted or unsubstituted heteroaryl group. In the above general formula (), M is a halogen atom or

[Formula] is a group. When M is a halogen atom, R ₆ COM represents an acid halide, and the halogen atom includes a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom without particular limitation. Industrially, acid chlorides or acid bromides in which M is a chlorine atom or a bromine atom are particularly preferably used. Also, M

[Formula] Place expressed as a group If, that is,

[Formula] represents an acid anhydride. Specific examples of acid halides that are generally suitable for industrial use include:
Acetic acid chloride, acetic acid bromide, chloroacetic acid chloride, dichloroacetic acid chloride, bromoacetic acid bromide, iodoacetic acid chloride, dibromoacetic acid chloride, methoxyacetic acid chloride, cyanoacetic acid chloride, trifluoroacetic acid fluoride, propionic acid chloride, chloropropionic acid chloride, bromopropion acid bromide,
Butyric acid chloride, chlorobutyric acid chloride, valeric acid chloride, chlorovaleric acid chloride, hexanoic acid chloride, acrylic acid chloride, butenoic acid chloride, chlorobutenoic acid chloride, pentenoic acid chloride, chloropentenoic acid chloride,
Phenoxyacetic acid chloride, chlorophenoxyacetic acid chloride, phenylpropionic acid chloride,
Furyl acrylic acid chloride, benzoic acid chloride, benzoic acid bromide, methylbenzoic acid chloride, ethylbenzoic acid bromide, chlorobenzoic acid chloride, fluorobenzoic acid fluoride,
Methoxybenzoic acid chloride, chloro(methyl)
Benzoic acid chloride, cyanobenzoic acid chloride, phenylbenzoic acid chloride, nitrobenzoic acid chloride, furoyl chloride, thiophenecarboxylic acid chloride, indolecarboxylic acid chloride, picolinic acid chloride, etc. are suitable. In addition, acid anhydrides include acetic anhydride, propionic anhydride, trifluoroacetic anhydride, chloroacetic anhydride,
Benzoic anhydride and the like are preferably used. Although the reaction of the raw materials in the present invention can be carried out without a solvent, it is generally preferable to carry out the reaction in a solvent. The solvent can be used without limitation as long as it is an inert organic solvent that does not interact with coexisting raw materials such as silane compounds and carboxylic acid derivatives. Generally, benzene, toluene, chloroform, acetonitrile, etc. are preferably used. The molar ratio of the raw materials to be charged in this reaction is not particularly limited, but considering the increase in by-products and economical efficiency, 1 to 2 moles of the silane compound and 1 to 2 moles of the silane compound and the carboxylic acid and 1 mole of Schiff base, respectively, are not particularly limited. Preferably, the derivatives are used in a proportion of 1 to 1.2 mol.
In particular, when a large amount of carboxylic acid derivative is used, side reactions tend to occur more easily, so it is preferable to determine the molar ratio of the raw materials to be charged in advance. Note that the Schiffz base compound used as a raw material in the present invention does not necessarily have to be isolated or purified.
That is, a Schiff base compound may be synthesized by the method described above, and then the other raw materials used in the present invention, such as a silane compound and a carboxylic acid derivative, may be added and reacted. In addition, the reaction temperature in the above reaction is not particularly limited and can be selected within a wide temperature range, but the reaction temperature may be selected in a suitable temperature range taking into account the chemical reactivity of the raw materials and the stability of the amide compound that is the product. It is preferable to carry out this process, and generally the temperature may be selected from the range of -20°C to 150°C. Furthermore, the reaction time varies depending on the reaction temperature, but generally ranges from several minutes to several days, e.g.
You can choose between minutes and 10 days. The order in which the raw materials represented by the general formulas (), (), and () of the present invention are added is not particularly limited and may be selected as necessary. Generally, the silane compound and the carboxylic acid derivative may be added to the Schiff base compound at room temperature or under cooling. Further, a Schiff base compound may be added to a solution of a silane compound and a carboxylic acid derivative. In these cases, a solvent is generally used in many cases, and three components, a Schiff base compound, a silane compound, and a carboxylic acid derivative, may be added and reacted in the solvent, and each component is dissolved in the solvent, and then the solvent may be added and mixed to react. In the present invention, the amide compound can be easily obtained by reacting the raw materials represented by the above general formulas () to (). The method for purifying the amide compound obtained by the above reaction is not particularly limited. Generally, after completion of the reaction, distillation at normal pressure, reduced pressure or vacuum may be carried out, and purification methods such as washing, recrystallization or chromatography may also be used as required. In addition, when the amide compound has a high boiling point, after the completion of the reaction, remove low boiling point components such as the solvent, dissolve it again in the solvent, wash with water or a dilute aqueous alkaline solution, and then remove the solvent. It is also possible to easily remove unreacted silane compounds, carboxylic acid derivatives, by-product silane compounds, and the like to obtain a pure target amide compound. (Functions and Effects) The chemical formula of the reaction of the present invention is as follows. Although the reaction mechanism of the above reaction is not clear, it is inferred as follows. First, one reaction mechanism is that in the presence of a silane compound, a Schiff base compound and a carboxylic acid derivative interact, forming an immonium salt type compound as an intermediate.

[Formula] or its M adduct It is thought that the desired amide compound is produced by further reacting these compounds with the silane compound. Another reaction mechanism is that a Schiff base compound and a silane compound first react to form an N-silyl compound.

It is possible that [Formula] is formed and then an amidation reaction occurs. The amide compound obtained by the method of the present invention is useful, for example, as agrochemicals such as herbicides, insecticides, and fungicides, or as pharmaceuticals. It is also a useful substance as an intermediate raw material for these uses. As described above, the method of the present invention is an excellent method capable of synthesizing amide compounds useful for medicines and agrochemicals from the corresponding Schiff base compounds under mild conditions, in high yield, and in one step. . Furthermore, the product can be easily purified after the reaction is completed. Therefore, it can be said that the present invention is extremely excellent from an industrial perspective. (Examples) Examples and reference examples for specifically explaining the present invention are listed below, but the present invention is not limited to these examples and reference examples. Example 1 Reference example 1 was placed in a three-necked flask equipped with a dropping funnel.
N-ethoxymethylidene(1-m-tolyl-2,2dimethyl)ethenylamine (2.11
g), anhydrous benzene (15 ml), and while stirring under ice cooling, add chloroacetyl chloride (1.20 g) and trichlorosilane (1.80 g) from the dropping funnel.
A solution of anhydrous benzene (5 ml) was added dropwise. After the dropwise addition was completed, the temperature was returned to room temperature, and the mixture was stirred at room temperature for 1 hour. An aqueous potassium carbonate solution was added to the reaction solution to neutralize it, and the organic layer was extracted with ether. After drying the extract with sodium sulfate, the viscous liquid obtained by removing the solvent was purified using column chromatography (silica gel; eluted with benzene/acetone) to obtain a colorless viscous liquid (1.60 g). Obtained. When the infrared absorption spectrum of the compound was measured, absorption based on C-H bonds was observed at 3000 to 2850 cm ^-1 ;
Strong absorption based on the C=O bond of acid was observed at 1670 cm ^-1 . Also, when we measured the mass spectrum, we found that m/
Molecular ion peak (M) at e295, M at m/e260
- Peak corresponding to Cl, M at m/e250 -
Peak corresponding to OC ₂ H ₅ , M − at m/e236
Peak corresponding to CH ₂ OC ₂ H ₅ , M at m/e218
- Peaks corresponding to COCH ₂ Cl were shown. ¹ H-nuclear magnetic resonance spectrum (δ; ppm: tetramethylsilane standard, deuterated chloroform solvent) was measured. The analysis results are as follows. (a) 2.33ppm (s, 3H) (b) 7.08ppm (s, 4H) (c) 1.88ppm (s, 6H) (d) 4.13ppm (s, 2H) (e) 4.77ppm (d, d, 2H) (f) 3.62ppm (q, 2H) (g) 1.16ppm (t, 3H) Its elemental analysis values are C64.78%, H7.62%,
The N content was 4.76%, which was in good agreement with the calculated values of C64.97%, H7.50%, and N4.74% for the composition formula C ₁₆ H ₂₂ NClO ₂ (295.81). From the above results, it is clear that the isolated product is N-[1-(m-
The product was found to be tolyl-2,2-dimethylethenyl]-N-chloroacet-ethoxymethylamide. The yield was 56%. The compound No. of the compound is designated as 1. Example 2 N-ethylidene-(1-phenyl-
2,2-Dimethyl)ethenylamine (2.15 g) and acetonitrile (15 ml) were added, and while stirring at room temperature, a solution of chloroacetyl chloride (1.47 g) in acetonitrile (5 ml) was added dropwise from the dropping funnel, followed by trichlorosilane (2.17 g). g) was added dropwise. After the dropwise addition was completed, the mixture was heated and stirred on an oil bath (50°C) for 1 hour. After cooling to room temperature, the solvent and low-boiling components were distilled off under reduced pressure, the residue was neutralized with an aqueous sodium carbonate solution, and the organic layer was extracted with ether. The ether layer was dried with sodium sulfate, the ether was removed, and the resulting liquid was purified by column chromatography (silica gel; eluted with benzene/acetone) to obtain a pale yellow viscous liquid (1.84 g). . Instrumental analysis of the compound revealed that the product was a compound having the following structural formula.
The yield was 61%. This compound is referred to as Compound No. 2. Example 3 Various chloroacetamide compounds were synthesized in the same manner as in Examples 1 and 2. The number, structure, silane compound used, elemental analysis value, and yield of the synthesized compound are listed in Table 1. In addition, in the table
R ₁ , R ₂ , R ₃ , R ₄ , (-A) _o --R ₅ is R ₁ in the following formula,
R ₂ , R ₃ , R ₄ , (-A) _o --corresponds to R ₅ .

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[Table] Example 4 A solution of N-ethoxymethylidene-(1-phenyl-2,2-dimethyl)ethenylamine (2.10 g) in anhydrous toluene (15 ml) was placed in a flask.
Bromoacetyl bromide (2.30 g) was added to anhydrous toluene (5 ml) under nitrogen and stirring under ice-cooling.
The solution was added gradually. A solution of dichlorosilane (2.02 g) in anhydrous toluene (10 ml) was then added. After dropping, return to room temperature, and then heat in an oil bath (40°C).
The mixture was heated and stirred for 1 hour at 30°C. After the reaction was completed, low-boiling substances were removed under reduced pressure, and the resulting viscous liquid was purified using column chromatography to obtain a pale yellow viscous liquid (1.51 g). Analysis of the compound revealed that the product was a compound having the following structural formula. The yield was 46%. The compound number of this compound is 42. Example 5 In a flask, N-ethylidene-(1-phenyl-2,2-dimethyl)ethenylamine (2.05 g,
A solution of acetic anhydride (1.32 g) and trichlorosilane (2.03 g) in anhydrous acetonitrile (10 ml) was added dropwise under nitrogen with stirring at room temperature. After heating and stirring in an oil bath (50°C) for 1 hour, the mixture was cooled to room temperature. The viscous liquid obtained by removing low-boiling substances under reduced pressure was purified using column chromatography to obtain a colorless viscous liquid (1.36 g). Analysis of the compound revealed that the product was a compound having the following structural formula. The yield was 53%. The No. of this compound is 43. Example 6 Amide compounds were synthesized using various Schiff base compounds, various silane compounds, and various carboxylic acid derivatives. The product number, structure, silane compound used, and yield are listed in Table 2. R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , A, n,
M and HSiXYZ are a substituent and a compound represented by the following formula.

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[Table] Reference Example 1 In a flask, m-tolyl-isopropylketimine (10.10g) and ethyl orthoxate (10.34g) were added to a flask.
g) was added thereto, and the mixture was heated and stirred in an oil bath (110°C) for 3 hours. The process was carried out while removing the alcohol produced. After cooling, the reaction solution was distilled to obtain a pale yellow liquid (7.10 g). Boiling point is 92-94
It was ℃/0.6mmHg. When the infrared absorption spectrum of the compound was measured, absorption based on C-H bonds was observed at 3100 to 2850 cm ^-1 ;
Absorption based on C=C bond at 1650cm ^-1 , 1625cm
^-1 showed strong absorption based on -N=CH-. Also, when we measured the mass spectrum, we found that m/
Molecular ion peak (M) at e217, M at m/e188
−Peak corresponding to C ₂ H ₅ , M − at m/e172
Peak corresponding to OC ₂ H ₅ , at m/e145

The peaks etc. corresponding to [Formula] are shown. ¹ H-nuclear magnetic resonance spectrum (δ; ppm: tetramethylsilane standard, deuterated chloroform solvent) was measured. The analysis results are as follows. (a)...2.30ppm (s, 3H) (b), (d)...6.80-7.33ppm (m, 5H) (c)...1.78ppm (d, 6H) (e)...4.20ppm (q, 2H) (f)...1.28ppm (t, 3H) Its elemental analysis is C77.25%, H8.78%, N6.50
%, which agreed well with the calculated values for C 77.38%, H 8.81%, and H 6.45% for the composition formula C ₁₄ H ₁₉ NO (217.30). From the above results, the isolated product is N-ethoxymethylidene (1-m-tolyl-2,2-dimethyl).
It turned out to be ethenylamine. The yield was 52%. The compound number of this compound is 118. Reference Example 2 Potassium hydride (3.50 g) and ether (40 ml) were placed in a flask, and then phenyl-isopropyl ketimine (10.25 g) was added. Acetaldehyde (4.63 g) was gradually added dropwise while stirring at room temperature. Thereafter, the mixture was heated and stirred in an oil bath (50°C) for 3 hours. After cooling to room temperature, the solid is filtered, low-boiling components are removed from the filtrate, and the resulting liquid is distilled under reduced pressure to obtain a pale yellow liquid (5.20
g) was obtained. The boiling point was 60-63°C/0.4mmHg. When the infrared absorption spectrum of the compound was measured, absorption based on C-H bonds was observed at 3050 to 2850 cm ^-1 .
Absorption based on C=C bond at 1650cm ^-1 , 1620cm
^-1 shows absorption based on =C=H- bond. Also, when we measured the mass spectrum, we found that m/
Molecular ion peak (M) at e173, m/e131

The peaks etc. corresponding to [Formula] are shown. ¹ H-nuclear magnetic resonance spectrum (δ; ppm: tetramethylsilane standard, deuterium chloroform solvent) was measured and analyzed. The results are as follows. (a), (c)...7.40-6.82ppm (m, 6H) (b)...1.82ppm (d, 6H) (d)...1.93ppm (d, 3H) The elemental analysis value is C83.40%, H8.60%,
The N content was 8.16%, which was in good agreement with the calculated values of C83.19%, H8.73%, and N8.09% for the composition formula C ₁₂ H ₁₅ N (173.25). The above results revealed that the isolated product was N-ethylidene(1-phenyl-2,2-dimethyl)ethenylamine. The yield was 43%. The compound number of this compound is designated as 119. Reference Example 3 3-oxobutyraldehyde, dimethyl acetal (8.50 g), and phenyl-isopropyl ketimine (5.11 g) were placed in a flask, equipped with a methanol removal device, and heated and stirred in an oil bath (120°C) for 7 hours. . After cooling to room temperature, low-boiling components are removed and the resulting liquid is distilled under reduced pressure.
A yellow viscous liquid (4.77g) was obtained. Boiling point is 115-118
The temperature was ℃/0.5mmHg. Instrumental analysis of the isolated product revealed that it was the desired compound having the following structural formula. The yield was 64%. Compound No. of the compound
Set it to 120. Reference Example 4 Various oxygen-containing Schiff base compounds were synthesized in the same manner as in Reference Example 1. No. of the synthesized compound,
Structural aspects, boiling points, and yields are listed in Table 3.
In addition, R ₁ , R ₄ and R ₅ in the formula are R ₁ , R ₄ and R 5 in the following formula.
It corresponds to _R5 .

【table】

[Table] Reference Example 5 Various Schiff base compounds were synthesized in the same manner as in Reference Examples 1 to 3. The numbers, structures, and elemental analysis values of the synthesized compounds are listed in Table 4. In addition,
R ₁ , R ₂ , R ₃ , R ₄ , (-A) _o --R ₅ in the table are the following formulas
These correspond to R ₁ , R ₂ , R ₃ , R ₄ , (-A) _o --R ₅ .

【table】

【table】

【table】

【table】

【table】

【table】

【table】

【table】

【table】

【table】

【table】

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【table】

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【table】

Claims (1)

[Claims] 1 (a) General formula () (In the formula, R ₁ represents a substituted or unsubstituted aryl group or a substituted or unsubstituted heteroaryl group, and R ₂ and R ₃ are the same or different hydrogen atoms or carbon atoms of 1 to 6 represents an alkyl group, R ₂ and R ₃ may be interconnected to form a cyclic alkylene group, and R ₄ is a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 8 carbon atoms; represents a group, or a substituted or unsubstituted aryl group,
R ₅ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, A represents an oxygen atom or a sulfur atom, and n represents 0 or 1. However, when R ₅ is a hydrogen atom, n is 0. ) A Schiff base compound represented by (b) a silane compound represented by the general formula ( ) HSiXYZ (wherein X, Y, and Z are the same or different hydrogen atoms or halogen atoms), and (c) General formula () R ₆ COM (wherein R ₆ is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group, M is a halogen atom or a group [formula]. (In the formula, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , A, and n are the same as above.) A method for producing an amide compound represented by the following.