JPH0529027B2 - - Google Patents

Description

[Detailed description of the invention]

(Industrial Application Field) The present invention relates to a method for producing a heteroaromatic glyogyzalylic acid halide by reacting a heteroaromatic compound with oxalyl halide. (Prior Art and Problems to be Solved by the Invention) Heteroaromatic glyogyzalic acid halide is a compound useful as an agricultural pharmaceutical intermediate or an organic synthesis reagent. However, despite its usefulness, there have been very few synthesis examples. As one of the few examples, Belgian Patent No. 896054 shows a synthetic example of the following formula. [However, Y is S, Se, O, >N-R'' (However, R'' is an alkyl group or an aryl group.)
R ₃ , R ₄ and R ₅ are a hydrogen atom, an alkyl group, an aryl group or a halogen atom. ] However, since this synthesis method does not use a catalyst, the yield of heteroaromatic glyogyzalic acid halide is relatively high when the reaction is carried out under reflux conditions, but when the reaction is carried out at a low temperature below room temperature, especially below 15°C, the yield will be increased as described below. As is clear from the comparative example
It is only about 0.3%. Therefore, the present inventors have conducted intensive research to develop a new method for producing heteroaromatic glyogyzalic acid halide that is simple and can be applied over a wide range of areas. discovered that heteroaromatic glyogyzalic acid halide can be obtained in high yield by
Already suggested. (Patent Application No. 58-244345) As a result of further research, the present inventors found that
By initiating the reaction between the heteroaromatic compound and oxalyl halide after or while introducing hydrogen halide into the liquid phase, the reaction can be performed both under reflux conditions and at low temperatures. The inventors also discovered that heteroaromatic glyogyzalic acid halide can be obtained in high yield, leading them to propose the present invention. (Means for Solving the Problems) The present invention provides a method for reacting a heteroaromatic compound represented by the general formula (1) or (2) described later with oxalyl halide, and then reacting the compound represented by the general formula (3) or ( In the method for producing the heteroaromatic glyogyzalylic acid halide represented by 4), the reaction between the heteroaromatic compound and ogizalyl halide is started after or while introducing hydrogen halide into the liquid phase. This is a method for producing a heteroaromatic glyogyzalic acid halide represented by the general formula (3) or (4). Specific examples of typical heteroaromatic compounds generally suitably used in the present invention are as follows. That is, the general formula, or [However, Y ₁ , Y ₂ , Y ₃ , Y ₄ , Y ₅ and Y ₆ are the same or different hydrogen atoms, halogen atoms, nitrotro groups, cyano groups, hydrocarbon residues, halogen-containing hydrocarbon residues, Indicates an oxygen-containing hydrocarbon residue, a sulfur-containing hydrocarbon residue, or a nitrogen-containing hydrocarbon residue, where Z is an oxygen atom, a sulfur atom, or N-R (wherein, R is a hydrogen atom,
Alkyl group, unsubstituted or substituted phenyl group,
or a phenyl alkyl group. ) is shown. ] This is a compound represented by The halogen atoms for Y ₁ to _{Y 6} in the above general formulas (1) and (2) are chlorine atoms, bromine atoms, iodine atoms,
Fluorine atoms can be used without particular limitation. In addition, as the hydrocarbon residue, an alkyl group or an alkenyl group can be used without particular restriction, and generally has 1 to 12 carbon atoms.
In particular, 1 to 6 linear, branched or cyclic saturated or unsaturated groups are suitable. More specific examples of particularly preferably used groups include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t
-butyl group, n-pentyl group, n-hexyl group,
Allyl group, 3-butenyl group, 2-hexenyl group,
Examples include cyclohexenyl group, ethynyl group, and cyclopropylmethyl group. Furthermore, halogen-containing hydrocarbon residues such as halogenoalkyl groups or halogenoalkenyl groups can also be used without particular restriction, and generally have 1 to 12 carbon atoms.
, preferably 1 to 6 linear, branched or cyclic saturated or unsaturated halogen-containing hydrocarbon residues. As the halogen atom, those to which chlorine, bromine, iodine, or fluorine are bonded can be used. More specific examples of halogen-containing hydrocarbon residues that are preferably used include chloromethyl group,
Bromomethyl group, 1-chloroethyl group, 2-chloroethyl group, 4-bromobutyl group, trifluoromethyl group, 2-chlorovinyl group, 2-chloro-
Examples include 1,2-difluorovinyl group. In addition, oxygen-containing hydrocarbon residues such as alkoxy groups, alkoxyalkyl groups, and alkoxycarbonylalkyl groups can also be used without particular restriction, and are generally straight-chain carbon atoms having 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms,
Branched or cyclic saturated or unsaturated oxygenated hydrocarbon residues are preferred. More specific examples of oxygen-containing hydrocarbon residues that are preferably used include methoxy group, ethoxy group, n-propoxy group, t-
Alkoxy groups such as butoxy group, n-pentoxy group, n-hexoxy group, allyloxy group, cyclopropylmethoxy group; methoxymethyl group, ethoxymethyl group, t-butoxymethyl group, allyloxymethyl group, methoxyethyl group, ethoxyethyl group An alkoxyalkyl group such as a group, isopropoxyethyl group, diethoxymethyl group, epoxymethyl group, or tetrahydrofurfuryloxymethyl group is preferably used. In addition, methoxycarbonylmethyl group (-CH ₂ COOCH ₃ ), ethoxycarbonylmethyl group (-CH ₂ COOC ₂ H ₅ ), propoxycarbonylethyl group (-CH ₂ CH ₂ COOC ₃ H ₇ ),

[Formula] −CH= CH ₂ COOC ₂ H ₅ ,

Alkoxycarbonylalkyl groups such as [Formula] are preferred. Furthermore, sulfur-containing hydrocarbon residues can also be used without particular limitation. In general, a linear, branched or cyclic saturated or unsaturated sulfur-containing hydrocarbon residue having 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms, may be used. Particularly preferably used sulfur-containing hydrocarbon residues are alkylthio groups or alkenylthio groups such as methylthio, ethylthio, and allylthio groups. Furthermore, nitrogen-containing hydrocarbon residues can also be used without particular limitation, and are generally linear, branched, or cyclic saturated or unsaturated nitrogen-containing residues having 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms. Hydrocarbon residues are preferably used. More specific examples of nitrogen-containing hydrocarbon residues that are particularly preferably used include, for example, -
_CH2CN ,

[Formula] −CH ₂ CH ₂ CN,

[Formula] Cyanoalkyl group such as -CH=CHCN; dimethylaminomethyl group (-CH ₂ N
(CH ₃ ) ₂ ), dimethylaminoethyl group (-
Examples include dialkylaminoalkyl groups such as _CH2CH2N ( _{CH3 ) 2} ) and _{diethylaminoethyl} group ( _-CH2CH2N ( _C2H5 ) _{2 )} . Furthermore, even if the hydrocarbon residue, halogen-containing hydrocarbon residue, oxygen-containing hydrocarbon residue, sulfur-containing hydrocarbon residue, and nitrogen-containing hydrocarbon residue have an aromatic hydrocarbon residue, good. Examples of the above-mentioned groups having an aromatic hydrocarbon residue preferably used in the present invention are as follows. For example, phenyl group, phenyl alkyl group,
Phenyloxy group, phenylthio group, phenylalkyloxy group, phenyloxyalkyl group, phenylalkyloxyalkyl group, or phenylthioalkyl group, or an alkyl group, halogenoalkyl group, or alkoxy group in the benzene ring of each of these groups. , an alkoxycarbonyl group, a halogen atom, a nitro group, a cyano group, and the like. To give a more specific example,

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[Formula] etc. Furthermore, the same groups as those described above can be applied to the alkyl group, unsubstituted or substituted phenyl group, and phenylalkyl group represented by R in the general formulas (1) and (2). In the heteroaromatic compounds represented by the general formulas (1) and (2), the substituents represented by Y ₁ to Y ₆ are hydrogen atoms,
When a compound is an alkyl group, an alkoxy group, an alkoxyalkyl group, or an alkoxycarbonylalkyl group, the reaction with oxalyl halide starts extremely easily by introducing hydrogen halide, Since it has a large effect, it is particularly preferably used in the present invention. Another raw material used in the present invention is oxalyl halide. As the halogen atom of the oxalyl halide, chlorine, bromine, iodine, and fluorine atoms can be used without particular limitation, but chlorine, bromine, and fluorine atoms are particularly preferred. The method for producing the heteroaromatic glyogyzalic acid halide in the present invention is expressed by the following formula. or (However, in the above formulas (3) and (4), Y ₁ to Y ₆ and Z are the same as in the above general formulas (1) and (2), and X is a halogen atom.) The above-mentioned heteroaromatic compound Once the reaction between oxalyl and oxalyl halide starts, hydrogen halide is generated. However, apart from the hydrogen halide generated by the reaction of both of the above raw materials, by starting the reaction of both of the above raw materials in the presence of hydrogen halide, the desired heteroaromatic glyogyzalic acid halide can be produced. The present inventors have found that can be obtained in high yield. Therefore, the greatest feature of the present invention is that the reaction of both of the above raw materials is started after or while introducing hydrogen halide into the liquid phase. The hydrogen halide used in the present invention is
Any of hydrogen chloride, hydrogen bromide, hydrogen iodide, and hydrogen fluoride can be used. Among these, hydrogen chloride is most preferred. Further, hydrogen halide in either liquid or gaseous state can be used. The amount of hydrogen halide introduced into the liquid phase may be appropriately determined as necessary. Usually, it is preferable to introduce hydrogen halide so that it is present in the liquid phase in a molar ratio of 0.001 to 30, preferably 0.01 to 10, relative to the heteroaromatic compound. When the hydrogen halide mentioned above is liquid under the reaction conditions, it can be introduced by dissolving it in the liquid phase. In the case of a gas, hydrogen halide can be introduced into the liquid phase at a saturation concentration by blowing the hydrogen halide into the liquid phase. In the present invention, hydrogen halide only needs to be present at the start of the reaction between the heteroaromatic compound and oxalyl halide. Therefore, the reaction of both of the above raw materials may be started after introducing hydrogen halide into the liquid phase, or the reaction may be started while introducing hydrogen halide into the liquid phase. However, when the reaction is carried out at a high temperature, the hydrogen halide may volatilize, so in this case it is preferable to start the reaction while introducing the hydrogen halide into the liquid phase. In the present invention, the order of adding the raw materials and hydrogen halide may be any order as long as the raw materials start reacting with each other in the presence of hydrogen halide. For example, when the reaction is started by mixing raw materials, hydrogen halide may be dissolved in a solvent in advance and then the raw materials may be added, or one of the raw materials may be added to the solvent. Examples include a method in which one of the raw materials is dissolved, then hydrogen halide is introduced, and then the other raw material is added. Alternatively, it is also possible to adopt a method in which hydrogen halide is introduced after mixing the raw materials at such a low temperature that the reaction does not start even if the raw materials are mixed, and then the temperature is raised to the reaction temperature to start the reaction. The liquid phase into which the hydrogen halide is introduced is composed of the raw material itself when no solvent is used, and when a solvent is used, it is composed of the solvent in which the raw material is dissolved or not dissolved. In the present invention, the molar ratio of the heteroaromatic compound and oxalyl halide to be charged may be appropriately determined as necessary. Generally, oxalyl halide is used in a slight excess molar amount per mole of the heteroaromatic compound. Although a solvent is not necessarily required for the reaction in the present invention, it is generally preferable to use an organic solvent. As the organic solvent, any solvent that is inert under the reaction conditions may be used without particular limitation. Examples of those generally suitably used are as follows. That is, aliphatic or aromatic hydrocarbons such as benzene, toluene, xylene, monochlorobenzene, dichlorobenzene, nitrobenzene, hexane, heptane, petroleum ether, chloroform, methylene chloride, ethylene chloride, dibromotetrafluoroethane, or halogens. Hydrocarbons; Ethers such as diethyl ether, dioxane, and tetrahydrofuran; Ketones such as acetone and methyl ethyl ketone; Nitriles such as acetonitrile; Amides such as N,N-dimethylformamide and N-methylpyrrolidone; Dimethyl sulfoxide; Nitromethane; carbon disulfide, etc. are preferably used. The reaction temperature in the present invention cannot be absolutely limited, but can generally be appropriately selected from a wide range. Generally, the temperature may be selected from the range of -70°C to 250°C, preferably -30°C to 120°C. especially,
At a low temperature below room temperature, for example below 15℃,
The effects of the present invention are noticeable. Although the reaction time varies depending on various conditions, it may be selected from the range of usually 5 minutes to 10 days, preferably 30 minutes to 5 days. Furthermore, it is preferable that the reaction yarn be stirred during the reaction. As a method for isolating and producing the target product of the present invention, that is, heteroaromatic glyogyzalic acid halide, known methods such as distillation, recrystallization, etc. can be applied. However, if the heteroaromatic glyogyzalic acid halide produced is unstable, it is possible to remove low-boiling substances under reduced pressure after the reaction and then use it as a raw material for the next reaction without purification. . The structure of the heteroaromatic glyogyzalic acid halide obtained in the present invention can be confirmed by the following means. (b) By measuring the infrared absorption spectrum (IR), it was found that the absorption based on CH bond is near 3100 to 2800 cm ^-1 and the carbonyl bond of acid halide is near 1760 to 1780 cm ^-1 (however, the halogen atom is a fluorine atom). , a characteristic absorption based on the keto group carbonyl bond at the α-position can be observed at 1650 ^{to 1700 cm -1 .} (b) Measure the mass spectrum (mS) and calculate 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 charge number e). According to
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 The molecular weight of can be determined. Furthermore, for example, if X is represented by a chlorine atom, M - COCl, M
-Characteristic strong peaks corresponding to COCOCl and COCl are observed, and the binding mode of the molecules can be known. (c) By measuring ¹ H-nuclear magnetic resonance spectrum ( ¹ H-nmr), it is possible to know the bonding mode of hydrogen atoms present in the heteroaromatic glyogyzalic acid halide. Summarizing the ¹ H-nmr characteristics of the compound, the protons of the furan ring, thiophene ring, benzofuran ring, or benzothiophene ring tend to show a characteristic peak at 6.3 to 8.0 ppm. Also, furan ring, thiophene ring, pyrrole ring,
When a proton is contained in the substituent Y ₁ , Y ₂ , Y ₃ , Y ₄ , Y ₅ or Y ₆ of the benzofuran ring, benzothiophene ring or indole ring, a corresponding proton peak will appear depending on its nature. . For example Y ₁ , Y ₂ , Y ₃ , Y ₄ , Y ₅ or Y ₆
When is an alkyl group, it shows a characteristic peak corresponding to the nature and number of protons contained in the alkyl group, for example, in the case of a methyl group,
It shows a characteristic peak around 2.2 to 2.6 ppm. (d) Heteroaromatic glyogyzalic acid halogenides are extremely reactive, and some of them are difficult to perform elemental analysis on, for example, because they react immediately with moisture in the air. In such a case, the compound can be determined by using another stable compound and analyzing this stable compound. For example, when alcohols or amines are applied to the compound, the reaction easily proceeds,
The respective corresponding ester or amide compounds can be obtained. The compositional formula of the ester compound or amide compound can be determined by elemental analysis, and in conjunction with the measurement results of the infrared absorption spectrum, mass spectrum, ¹ H and ¹³ C nuclear magnetic resonance spectrum of these compounds. The compositional formula and structure of each of the above compounds can be determined. The properties of the heteroaromatic glyogyzalic acid halide compound obtained in the present invention vary depending on the type of substituent, but in general, it is a pale yellow or yellow viscous liquid or solid at room temperature and normal pressure, and has a high boiling point. Many of them tend to decompose when they reach a certain temperature or higher. Moreover, the compound is highly reactive and reacts very easily with water, alcohols, amines, etc., for example. The compound is also soluble in inert solvents such as benzene, ether, chloroform, and carbon tetrachloride. The heteroaromatic glyogyzalic acid halide produced in the present invention is an extremely excellent compound that can be widely used as an agricultural chemical intermediate or an organic synthesis reagent. For example, heteroaromatic glyogyzalic acid can be obtained by reacting with water. Further, by reacting with alcohols or phenols, heteroaromatic glyogysalic acid esters can be obtained. In addition, heteroaromatic glyogyzalic acid amide can be obtained by reacting with amines.
These obtained acids and esters can be used as fungicides, and amides can be used in a variety of ways as herbicides and antibacterial agents such as cephalosporins typified by cefuroxime. (Effects) According to the method of the present invention, heteroaromatic glyogyzalic acid halide, which is an important compound in the field of agricultural medicine or organic synthesis, can be obtained in a short time and in good yield. Moreover, the method of the present invention can be used not only when the reaction temperature is relatively high, such as below the reflux temperature of the liquid phase, but also at low temperatures, such as temperatures below 15°C, where the reaction is difficult to proceed. can be obtained in good yield. Therefore, the present invention is an extremely important and useful method in the field of agricultural medicine or organic synthesis. Examples are given below to further specifically explain the present invention, but the present invention is not limited to these Examples. Example 1 Synthesis of 3-methylthiophene glyogyzalic acid glolide In a 300 ml three-necked flask, 200 g of chloroform, 3
- 9.8 g of methylthiophene was added, and while heating under reflux, hydrogen chloride gas was blown in at a rate of 150 ml per minute for 30 minutes. Next, 15 g of oxalyl chloride was added to this solution (hydrogen chloride was present in an amount of 0.5 mol per 1 mol of 3-methylthiophene), and the solution was heated under reflux for 5 hours while blowing hydrogen chloride gas. After removing low-boiling substances from the reaction solution under reduced pressure at room temperature, 17.6 g of residual 3-methylthiophene glyogyzalic acid chloride was obtained. (Yield 93.4%, boiling point 93℃/0.1mmHg) Example 2 200g of chloroform in a 300ml 3-necked flask, 3
- 9.8 g of methylthiophene was added, and hydrogen chloride gas was blown in at a rate of 150 ml per minute for 10 minutes at 0°C.
Next, 15 g of oxalyl chloride was added to this solution (hydrogen chloride was present in an amount of 0.3 mol per 1 mol of 3-methylthiophene), and the mixture was reacted at 0° C. for 24 hours while blowing hydrogen chloride gas. The yield of 3-methylthiophene glyogyzalic acid chloride was 44.2%. Note that the yield when hydrogen chloride gas was not blown was 0.3%. Example 3 80 g of benzene and 15 g of oxalyl chloride were placed in a 200 ml three-necked flask, and hydrogen chloride gas was blown into the flask at a rate of 150 ml per minute at room temperature for 30 minutes. Next, 6.8 g of furan was added to this solution (hydrogen chloride present in an amount of 0.4 mol per 1 mol of furan), and the mixture was allowed to react for 2 days at room temperature while blowing hydrogen chloride gas. Next, low-boiling substances were removed under reduced pressure at room temperature to obtain 8.4 g of furangliogyzalic acid chloride. (Yield 53.0%, boiling point 69
(°C/0.15 mmHg) The reaction was carried out under the same conditions except that hydrogen chloride gas was not blown, but only the raw material was recovered. Next, 8.4 g of the obtained furanglioguizalic acid chloride was dissolved in 200 ml of chloroform, and 9.2 g of 3,4-dichlorobenzylamine and 5.3 g of triethylamine were dissolved in 30 ml of chloroform under ice cooling. dripped. After stirring at room temperature for 3 hours and heating under reflux for an additional 30 minutes, the mixture was transferred to a separatory funnel, washed with 100 ml of diluted hydrochloric acid and then with 100 ml of water, and the chloroform layer was dried with Glauber's salt. By removing chloroform and recrystallizing from benzene, 13.9 g of white crystals of furangliogyzalic acid-3,4-dichlorobenzylamide were obtained. [Melting point 133-135°C Yield (furan basis) 46.6%] Example 4 Placed in a 300ml Teflon autoclave under ice cooling for 1.
Add 150 g of 1,2-trichloro-1,2,2-trifluoroethane, 0.8 g of hydrogen fluoride, and 4.1 g of 2-methylfuran, stir for 10 minutes, then add 7.5 g of oxalyl chloride and cool on ice for 4 hours. Stirred. Then, by removing low-boiling substances under reduced pressure at room temperature, 5
- 7.2 g of methylfurangliogyzalic acid chloride was obtained. (Yield 83.5%, boiling point 77℃/0.2mmHg) Example 5 Put 150g of ether and 15g of oxalyl chloride into a 300ml three-necked flask and add hydrogen chloride gas at room temperature for 30 minutes.
It blew for a minute. Next, this solution (hydrogen chloride is 2-
3.7 mol per 1 mol of methylthiophene)
9.8 g of 2-methylthiophene was added to the solution, and the mixture was stirred for 2 days at room temperature while blowing hydrogen chloride gas. Next, low-boiling substances were removed under reduced pressure to obtain 12.6 g of 5-methylthiophene glyogyzalic acid chloride. Yield 66.8
%, boiling point 93℃/0.1mmHg) Example 6 The same operation as in Example 1 was performed except that 3g of 3-methoxythiophene was used as the raw material, and 3-methoxy 4.5 g of thiofenglyogyzalyl chloride was obtained. (Yield: 83.6%) The infrared absorption spectrum of this product was measured, and it was confirmed that it exhibited strong absorption at 1770 cm ^-1 and 1660 cm ^-1 based on the carbonyl bond of the acid chloride and the α-keto group, respectively. Also, when mass spectra were measured, m/
Molecular ion peaks M were shown at e204 and 206, and a peak corresponding to M-COCl was shown at m/e141. In addition, ¹ H-nuclear magnetic resonance spectrum (δppm; based on tetramethylsilane, in deuterium chloroform solvent)
The results of the measurements were as follows. A single line for 3 protons is shown at 3.98ppm, (a)
corresponded to the methyl proton of the methoxy group.
The double line for one proton is shown at 6.96ppm, and the double line for one proton is shown at 7.75ppm, (b) and (c), respectively.
It corresponded to the proton of the thiophene ring corresponding to . From the above results, it was confirmed that the obtained compound was 3-methoxythiophene glyogizalic acid chloride. Next, 4.5 g of the obtained 3-methoxythiophene glyogyzalic acid chloride was added with 30 g of ethanol under ice-cooling.
After stirring at room temperature for 2 hours, the ethanol was removed under reduced pressure and the residue was distilled under reduced pressure to obtain 3-methoxythiophene, which was a pale yellow liquid at the time of distillation, but quickly turned reddish-purple. 4.3 g of ethyl glyogyzalate was obtained. [Boiling point 144℃/0.3mmHg yield (3-
Methoxythiophene standard) 76.4%] The infrared absorption spectrum of this material was measured.
Ester group and α at 1730cm ^-1 and 1630cm ^-1 respectively
- It was confirmed that strong absorption was observed due to the carbonyl bond of the keto group. Also, when the mass spectrum was measured, m/e214
Molecular ion peak M at m/e141, M − at m/e141
_A peak corresponding to _COOC2H5 was shown. In addition, ¹ H-nuclear magnetic resonance spectrum (δ; ppm:
Tetramethylsilane standard, deuterated chloroform solvent)
The results of the measurements were as follows. A triplet line corresponding to three protons was shown at 1.37 ppm, which corresponded to the methyl proton in (a'). A single line corresponding to three protons was shown at 3.95 ppm, which corresponded to the methyl proton of the methoxy group in (b'). A quadruple line of two protons was observed at 4.36 ppm, which corresponded to the methylene proton of (c'). Also, a double line corresponding to one proton was shown at 6.91 ppm, and a double line corresponding to one proton was shown at 7.79 ppm, which corresponded to the protons of the thiophene ring corresponding to (d') and (e'), respectively. In addition, its elemental analysis values are C50.20% and H4.78%, which are calculated values for C ₉ H ₁₀ O ₄ S (214.23).
It matched well with C50.46% and H4.71%. From the above results, it was confirmed that the obtained compound was ethyl 3-methoxythiophene glyogyzalate. Example 7 A reaction was carried out in the same manner as in Example 1 except that methyl β-(2-furyl)propionate was used in place of 3-methylthiophene in Example 1, and a viscous liquid 5 was obtained as a product. -2′-Methoxycarbonylethylfurangliogyzalic acid chloride 22
I got g. Yield 89.9%. The infrared absorption spectrum of this product was measured and it was confirmed that the carbonyl bond of the acid chloride exhibits strong absorption at 1770 cm ^-1 . Next, 100 ml of ethanol was slowly added to 22 g of the obtained 5-2'-methoxycarbonylethylfurangliogizalic acid chloride under ice cooling, and the mixture was heated at room temperature for 30 minutes.
After stirring for an hour, methanol was removed, and the residue was recrystallized from methanol to obtain 17.3 g of pale yellow crystals having the structure shown below. Melting point 55-56℃ Isolated yield (based on methyl β-(2-furyl)propionate) 72.1% Its elemental analysis values are C54.92%, H5.00%.
C55.00 which is the calculated value for C ₁₁ H ₁₂ O ₆ (240.22)
%, in good agreement with H5.04%. The results of other instrumental analyzes also indicated that the product had the above structure. From this result as well, it was confirmed that the compound before reacting with methanol was 5-2'-methoxycarbonylethylfurangliogyzalic acid chloride. Example 8 By a method similar to that described in detail in Example 1, a heteroaromatic compound and oxalyl halide were mixed in the presence of hydrogen halide (hydrogen halide was 0.01 to 1 mole of heteroaromatic compound). (10 mol) and reacted under various conditions. The results are shown in Table 1. As a result of measuring the obtained heteroaromatic glyogyzalic acid halide by infrared absorption spectrum, the acid chloride was 1760
~1780 cm ^-1 , acid fluoride has absorption based on carbonyl bond at 1800-1880 cm ^-1 and α at 1650-1700 cm ^-1
Absorption based on the carbonyl bond of the keto group at the - position was observed. Based on this result and the mass spectrum measurement results, it was confirmed that the obtained compound was a heteroaromatic glyogyzalic acid halide. Next, the same operation as in Example 1 was performed, and the yield of isolated ethyl ester is also shown in Table 1. Furthermore, in Table 1,

X of the group represented by [Formula] is oxalyl halide.

The same halo as X when expressed by [formula] Indicates a gen atom.

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[Claims]

1 After adding and mixing 5 to 50 parts by weight of maleic acid as a water removing agent to 100 parts by weight of monoammonium salt of maleic acid or maleic acid half amide,
A method for producing N-substituted maleimide, which comprises introducing superheated steam at 400°C.

Claims (1)

(In the formula, Y ₁ to _{Y 6} and Z are the same as the above general formulas (1) and (2), and X is a halogen atom.) The general formula is characterized in that the reaction between the heteroaromatic compound of general formula (1) or (2) and oxalyl halide is started after or while introducing hydrogen halide into the liquid phase. A method for producing the heteroaromatic glyogyzalic acid halide of (3) or (4).