JPS61291566A - Production of heterocyclic aromatic glyoxalic acid halogenide - Google Patents

Abstract

PURPOSE:To obtain in a short time in high yield the titled compound useful as an intermediate for agricultural chemicals and drugs and a reagent for organic syntheses, by starting a reaction between a heterocyclic aromatic compound and an oxalyl halogenide after or while introducing a hydrogen chloride to a liquid phase. CONSTITUTION:After or while a hydrogen halogenide (preferably hydrogen chloride) is introduced into a liquid phase, a reaction between a heterocyclic aromatic compound (e.g., 3-methylthiophene, etc.) and an oxalyl halogenide (e.g., oxalyl chloride) is started and the reaction is carried out to give a heterocyclic aromatic glyoxalic acid halogenide (e.g., 3-methylthiophene glyoxalic acid chloride, etc.). The reaction provides high yield both at low temperature or under reflux condition by this method.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for producing a heteroaromatic glyogideric acid halide by reacting a heteroaromatic compound with ogizalylnolognide.

(Prior Art and Problems to be Solved by the Invention) Heteroaromatic glyogideric acid no.10gnide is a metal compound useful as an agricultural drug 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 synthesis example of the following formula.

[However, Y is S I Se l Ol) N-R" (However, W' is an alkyl group or an aryl group.) R3, R4, and R5 are a hydrogen atom, an alkyl group, an aryl group, or a halodane group. However, since this synthesis method does not use a catalyst, the yield of heteroaromatic glyogideric acid halodanide is relatively high in the reaction under reflux conditions.
In the case of a reaction at a low temperature of .degree. C. or lower, the reaction rate is only about 0.3 degrees, as is clear from the comparative examples described later.

Therefore, the present inventors have conducted extensive research to develop a new method for producing heteroaromatic glyogidelic acid 10r nide that is simple and can be applied over a wide range of applications. We have already proposed that the heteroaromatic glyogideric acid halogedate can be obtained in high yield by using it as a compound. (Special application 1982-2443
No. 45) As a result of further research, the present inventors found that
By initiating the reaction between the heteroaromatic compound and the ogideryl no. The present inventors have discovered that heteroaromatic glyogideric acid halogenide can be obtained in high yield even when the compound is used, and the present invention has been proposed.

(Means for Solving the Problems) The present invention provides a method for producing heteroaromatic glyogidelic acid halide by reacting a heteroaromatic compound with ogideryl halide, in which hydrogen halide is brought into a liquid phase. This is a method for producing a heteroaromatic glyogideryl halide, which comprises starting a reaction between a heteroaromatic compound and ogideryl halide after or while introducing the heteroaromatic compound.

The following are specific examples of typical heteroaromatic compounds that are generally suitably used in the present invention.

That is, the general formula, ! 5 [However, Yl e Y2 + Y3 r Y4 , Y5
and Y6 are the same or different hydrogen atoms, respectively,)) a rogone atom, a nitro group, a cyano group, a hydrocarbon residue, a rhodane-containing hydrocarbon residue, an oxygen-containing hydrocarbon residue, a sulfur-containing hydrocarbon residue, Represents a nitrogen-containing hydrocarbon residue, and 2 represents an oxygen atom, a sulfur atom, or N-R (wherein R is a hydrogen atom, an alkyl group, an unsubstituted or substituted phenyl group, or a phenylalkyl group). . ] This is a compound represented by

The halodane atoms for Y and ~Y6 in the above general formulas (1) and (2) are chlorine atom, bromine atom, iodine atom, fluorine atom,
Elementary atoms can be used without particular limitations. In addition, the hydrocarbon residue can be an alkyl group or an alkenyl group without particular restriction, and is generally a linear, branched or cyclic saturated or unsaturated group having 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms. groups are preferred.

Examples of particularly preferably used groups include methyl group, ethyl group, n-propyl group, isobutyl group, n-
-butyl group, isobutyl group, t-butyl group, n-pentyl group, n-heΦyl group, allyl group, 3-putenyl group,
2-hexenyl group, cyclohexenyl group, ethynyl group,
Examples include cyclopropylmethyl group.

Further, halogen-containing hydrocarbon residues such as halodane alkyl groups or halo-alkenyl groups can also be used without particular limitation, and generally have 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms.
A linear, branched or cyclic saturated or unsaturated halogen-containing hydrocarbon residue is preferred. As the halodane atom, those to which chlorine, bromine, iodine, or fluorine are bonded can be used. The preferably used halodane-containing hydrocarbon residue is
More specific examples include chloromethyl group, bromomethyl group, 1-chloroethyl group, 2-chloroethyl group, 4-chloroethyl group,
Examples thereof include a bromobutyl group, a trifluoromethyl group, a 2-10 rubinyl group, a 2-/col-1,2-difluorovinyl group, and the like.

Also, alkoxy group, alkoxyalkyl group, a) recoxycal? Oxygen-containing carboxylic residues such as nyl alkyl groups can also be used without particular limitation, and are generally linear, branched or cyclic saturated or unsaturated groups having 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms. Saturated oxygenated hydrocarbon residues are preferred. More specific examples of oxygen-containing hydrocarbon residues that are preferably used include methoxy group, ethoxy group, n-glopoxy group, 1-butoxy group, n-pentoxy group, n-
Alkoxy groups such as hexoxy group, allyloxy group, cyclopropylmethoxy group; methoxymethyl group, ethoxymethyl group, t-butoxymethyl group, allyloxymethyl group, methoxyethyl group, ethoxyethyl group, isopropoxyethyl group, jetoxymethyl group group, epoxymethyl group,
Alkoxyalkyl groups such as tetrahydrofur7lyloxymethyl group are preferably used. In addition, methoxyl is a nylmethyl group (-0M2COOCR,), ethoxyl is a nylmethyl group (-CH2COOC2H5), ProJ
j? It is preferred that the middle radical is a nylethylcarmenylalkyl group.

Furthermore, sulfur-containing hydrocarbon residues can also be used without particular limitation. Generally 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms
It is preferable to use linear, branched or cyclic saturated or unsaturated sulfur-containing hydrocarbon residues. 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 restriction, and are generally linear, branched, or cyclic saturated or unsaturated nitrogen-containing carbonated residues having 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms. Hydrogen residues are preferably used. More specific examples of nitrogen-containing hydrocarbon residues that are particularly preferably used include:
For example, -CH2CN, cyanoalkyl group; dimethylaminomethyl group < -CH2N(CH3)2), dimethylaminoethyl group (-aH2cH2N(CH3)2), diethylaminoethyl group (-CH2CH2N(C2) (5
)2) and other dialkylaminoalkyl groups.

Furthermore, the hydrocarbon residue, halogen-containing hydrocarbon residue, oxygen-containing hydrocarbon residue, sulfur-containing hydrocarbon residue, and nitrogen-containing hydrocarbon residue may 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.

Examples: Eva, phenyl group, phenylalkyl group, phenyloxy group, phenylthio group, phenylalkyloxy group,
A phenylthioalkyl group, a phenylalkyloxyalkyl group, a phenylthioalkyl group, or an alkyl group, a halogenoalkyl group, an alkoxy group, an alkoxycarbunyl group, a norodane atom, a nitro group, or a cyano group in the benzene ring of each of these groups. etc. are bonded groups. To give a more specific example, the alkyl group, unsubstituted or substituted phenyl group, and phenylalkyl group represented by R in the above general formulas (1) and (2) are the same as those mentioned above. Groups can be applied.

In the heteroaromatic compounds represented by the above general formulas (1) and (2), the substituents represented by Y and ~Y6 are hydrogen atoms, alkyl groups, alkoxy groups, alkoxyalkyl groups, or alkoxycargenyl alkyl groups. A certain compound is particularly preferably used in the present invention because the reaction with ogideryl halonide is very easily initiated by introducing hydrogen halide, and the effect of introducing hydrogen halide is large.

Another raw material used in the present invention is oxalyl halide. As the halodane atom of the oxalyl halonide, 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 heteroaromatic glyogyzalic acid halodanide according to the present invention is expressed by the following formula.

or (However, in the formulas (3) and (4) above, Y1 to Y6 and 2
is the same as the above general formulas (1) and (2), and X is a halogen atom. ) Once the reaction between the above-mentioned heteroaromatic compound and ogideryl halonide 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 target heteroaromatic glyogidelic acid halide can be produced in high yield. The present inventors have found that the following can be obtained.

Therefore, the greatest feature of the present invention is that the reaction of both of the above raw materials is started after or while hydrogen halide is introduced into the liquid phase.

As the hydrogen halide used in the present invention, any of hydrogen chloride, hydrogen bromide, hydrogen iodide, and hydrogen fluoride can be used. Among these, hydrogen chloride is most preferred.

Furthermore, 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, the molar ratio of hydrogen halide to the heteroaromatic compound is 0.001.
It is suitable to introduce it so that it exists in the liquid phase in the range of 0.01 to 10, preferably 0.01 to 10.

When the hydrogen halide described above is liquid under the reaction conditions, the hydrogen halide can be introduced by dissolving it in the liquid phase. Also, in the case of gas,
By blowing hydrogen rhodanide into the liquid phase, a saturated concentration of hydrogen rhodanide can be introduced into the liquid phase.

In the present invention, it is sufficient that hydrogen rhodanide is present at the start of the reaction between the heteroaromatic compound and ogideryl halodanide. 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.

The order of addition of raw materials and hydrogen halides in the present invention is as follows:
Any order may be used as long as the raw materials start reacting with each other in the presence of hydrogen halide. for example,
If the reaction is started by mixing raw materials, the 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 dissolved in the solvent. Examples include a method in which 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 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 the ogideryl halide may be appropriately determined as necessary. Generally, ogideryl halodanide 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. The following examples are commonly used.

So, benzene, toluene, xylene, monochlorobenzene, dichlorobenzene, nitrobenzene, hexane,
Aliphatic or aromatic hydrocarbons or hydrogenated hydrocarbons such as hebutane, petroleum ether, chloroform, methylene chloride, ethylene chloride, and dibromotetrafluoroethane; ethers such as diethyl ether, dioxane, and tetrahydrofuran: Ketones such as acetone and methyl ethyl ketone; Nitriles such as acetonitrile: N, N
Amides such as -dimethylformamide and N-methylpyrrolidone; dimethylsulfoxide; 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, 10°C to 20°C, preferably 130°C to 12°C
It may be selected from the range of 0°C.

In particular, the effects of the present invention are noticeable at low temperatures below room temperature, for example below 15°C. 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 for the method for isolating and producing the target product of the present invention, that is, heteroaromatic glyogideric acid halide, known methods such as distillation, recrystallization, etc. can be applied.

However, if the heteroaromatic glyogyzalic acid halide produced is unstable, after the reaction is completed.

After removing low-boiling substances under reduced pressure, it is also possible to use the product as a raw material for the next reaction without purification.

The structure of the heteroaromatic glyogyzalic acid nide obtained in the present invention can be confirmed by the following means.

0) By measuring the infrared absorption spectrum (IR), it was found that the absorption based on CH bond is near 3100-2800 cm-1, and the carbinyl bond of acid halide is near 1760-1780 cm (however, if the halodane atom is a fluorine atom, the absorption based on CH bond is ~1880 cm-') and a characteristic absorption based on the carbinyl bond of the keto group at the α-position at 1650 to 1700 cm.

(b) Measure the mass spectrum (ms), and each peak observed (generally, the ion molecular weight m is expressed as the ion charge number 6
By calculating the corresponding composition formula (mass number expressed as m/e divided by . In other words, when a sample subjected to measurement is expressed by a general formula, the molecular ion peak (hereinafter abbreviated as -) is generally observed as an intensity ratio according to the isotope abundance ratio depending on the number of halodane atoms contained in the molecule. Therefore, the molecular weight of the compound subjected to measurement can be determined. Furthermore, for example, X represents a chlorine atom, Mo-COC2,
Characteristic strong peaks corresponding to Me-COCOCt and H-COCt'' were observed, allowing the binding mode of the molecules to be known.

(c) 1H-nuclear magnetic resonance spectrum ('H-nmr
) By measuring 6.
Substituent Y1. of the offene ring tends to show a characteristic peak at 3 to 8.0 ppm. Y2. Y3. Y4. When a proton is included in Y5 or Y6, a corresponding proton peak appears depending on its nature.

For example, ylt Y2# Y3. Y4. Y5 or Y
When 6 is an alkyl group, it exhibits 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, a characteristic peak appears around 2.2 to 2.6 ppm. shows.

(2) Heteroaromatic gliogidelic acid nitrides are extremely reactive and, for example, react readily with moisture in the air, making elemental analysis difficult. 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 reacted on the compound, the reaction proceeds easily and the corresponding ester compound or amide compound 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, H and C nuclear magnetic resonance spectra of these compounds. The compositional formula and structure of each of the above compounds can be determined.

The properties of the heteroaromatic glyogyzalic acid halodanide compound obtained by the present invention vary somewhat depending on the type of substituent, but it is generally a pale yellow or yellow viscous liquid or solid at room temperature and normal pressure, and has a high boiling point. It tends to decompose when the temperature exceeds a certain level. Furthermore, the compound is highly reactive and reacts very easily with water, alcohols, amines, etc., for example. Furthermore, the compound is soluble in inert solvents such as benzene, ether, chloroform, and carbon tetrachloride.

The heteroaromatic glyogideric acid halonide 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 glyogideric acid is obtained by reaction with water. In addition, by reacting with alcohols or phenols, heteroaromatic glyogideric acid ester A/ can be obtained. In addition, by reacting with amines, cyheteroaromatic glyogyzalic acid amide can be obtained.

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 such as cefoxime. can.

(Effects) By the method of the present invention, heteroaromatic glyogideric 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. In addition, 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 15°C or lower, where the reaction is difficult to proceed. Glyogideric acid halodanide 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 Examples will be given below to explain the present invention more specifically, but the present invention is not limited to these Examples.

Example 1 Synthesis of 3-methylthiophenegliogyzalic acid chloride In a 300d three-necked flask, chloroform 200I, 3-
9.81 I of methylthiophene was added, and while heating under reflux, hydrogen chloride gas was blown in at a rate of 150 d/min for 30 minutes. Next, this solution (hydrogen chloride is 3-methylthiophene 1
0.5 mol to mol) of ogideryl chloride 1
5 g was added, hydrogen chloride gas was blown into the solution, and the mixture was heated under reflux for 5 hours. After removing low-boiling substances from the reaction solution under reduced pressure at room temperature, residual 3-methylthiophene glyogyzalic acid chloride 17.6 F was obtained. (Yield: 93.4 cm, boiling point: 93°C
/ 0.1 wHg) Example 2 200I of chloroform in a 30QatJ flask
, 3-methylthiophene (9.81 g) was added thereto, and hydrogen chloride gas was blown in at a rate of 150 Wll/min for 10 minutes at 0°C. Next, in this solution (hydrogen chloride is present at 0.3 mol per 1 mol of 3-methylthiophene), 15 ogideryl chloride is added.
After adding J' and blowing in hydrogen chloride gas, it was heated to 24℃ at 0℃.
Allowed time to react.

The yield of 3-methylthio7-engliogyzalic acid chloride was 44.2%. . Note that the yield when the hydrogen chloride gas was not blown was 0.3%.

Example 3 15 g of benzene 8°Ol ogideryl chloride was placed in a 200 WL 13 flask, and hydrogen chloride gas was blown into the flask at a rate of 1501 d/min at room temperature for 30 minutes.

Next ° this solution (hydrogen chloride is 0 per mole of furan,
6.81 moles of furan was added to the solution (4 moles present) and reacted 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 8.41 of furangliogideryl chloride. (Yield: 53.0 cm, boiling point: 69°C/
0.15 mHg) The reaction was carried out under the same conditions except that hydrogen chloride gas was not blown into the reactor, but only the raw material was recovered.

Next, this obtained furangliogyzalic acid chloride 8.4
, F was dissolved in 200ml of chloroform and cooled with water.3.
4-Dichlorobenzylamine 9.2II,)! A solution of 5.31 J ethylamine dissolved in 39 d of chloroform was slowly added dropwise. After stirring at room temperature for 31 hours and heating under reflux for another 30 minutes, the mixture was transferred to a separatory funnel and diluted with 10% diluted hydrochloric acid.
01d, followed by washing with water Zoom, and drying the chloroform layer with Glauber's salt. By removing chloroform and recrystallizing with benzene, white crystals of fluorogylidelic acid were obtained.
13.9JF of 3,4-dichlorobenzylamide was obtained.

C melting point 133-135℃ Yield (furan standard) 46.6
%] Example 4 1.1.2 under water cooling in a 300d Teflon autoclave
-) dichloro-1,2,2-trifluoroethane 15
ON, 7 Hydrogen fluoride 0.8.9.2-Methylfuran 4.1
g and stirred for 10 minutes, then add oxalyl chloride 7
．． 5 II was added and stirred for 4 hours under water cooling.

Next, 7.2 g of 5-methylfurangliogyzalic acid chloride was obtained by removing low-boiling substances under reduced pressure at room temperature. (
Yield 83.5%, boiling point 77°C/0.2 wHg) Example 5 150 g of ether in 13 300 rn flasks.

15.9 g of ogideryl chloride was added and hydrogen chloride gas was blown in at room temperature for 30 minutes. Next, this solution (hydrogen chloride is 2-
3.7 mol per 1 mol of methylthiophene)
- 9.8 I of methylthiophene was added, 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°C/0.1 mHg) Example 6 The same operation as in Example 1 was performed except that 3-methoxythiophene 31I was used as the raw material, and low-boiling substances were removed under reduced pressure. 3-Methoxythiophenegliogidelic acid hydride 465y was obtained.

(Yield 83.6 cm) The infrared absorption spectrum of this material was measured.

It was confirmed that 1770 and 1660 K exhibited strong absorption based on the carzenyl bond of acid chloride and α-keto group, respectively.

Also, when the mass spectrum was measured, m/e 20
4.

Molecular ion peak Me at 206, M”- at m/e141
A peak corresponding to COO2 was shown.

Further, the H-nuclear magnetic resonance spectrum (δppm; in double chloroform solvent based on tetramethylsilane) was measured, and the results were as follows.

A single line for three 3.98ppmK protons is shown, (,
) corresponded to the methyl proton of the methoxy group.

6.96ppmK double line for one proton, 7.75p
A double line for one proton is shown at pm, and (b)
, corresponded to the proton of the thiophene ring corresponding to (0).

Based on the above results, it was confirmed that the obtained compound was 3-methoxythiophene glyogyzalic acid chloride.

Next, 3011 ethanol was slowly added to 4.5 J of the obtained 3-methoxythiophenegliogidelic acid chloride under water cooling, and after stirring at room temperature for 2 hours, the ethanol was removed under reduced pressure and the residue was distilled under reduced pressure. Ethyl 3-methoxythiophene glyogiderate 4,3I was obtained as a liquid that was pale yellow during distillation but soon turned reddish-purple. [Boiling point 144℃
/ 0.3 mHg yield (76.4% based on 3-methoxythiophene group) The infrared absorption spectra of this product were measured at 1730 ctn and 1630 cW1, respectively, indicating strong absorption based on the carbunyl bond of the ester group and α-keto group. It was confirmed that

In addition, when the mass spectrum was measured, m/e 214 molecules 4 y peak Me-m/@141 K PI”
A peak corresponding to -COOC2H5 was shown.

Further, the results of measurement of H-nuclear magnetic resonance spectrum (δ: ppm: 9-fold chloroform solvent based on tetramethylsilane) were as follows.

(b') Show the triplet line of 3 protons at 1.37 ppm a
’) corresponded to the methyl proton. A single line corresponding to 3 protons is shown at 3.95 ppm, and a quadruple line corresponding to 2 protons is shown at Pm (corresponding to the methyl protons of b methoxy groups. 4.361). It was equivalent to In addition, 6.91 pPm has two protons.
A double line corresponding to one proton is shown at 7.79 ppm, which corresponds to the proton of the thiophene ring corresponding to (d') and (e'), respectively.

The elemental analysis values were C50.20% and H4.78%, which agreed well with the calculated values for C, H1o04S (214,23), C50.46% and H4.71%.

From the above results, it was confirmed that the obtained compound was ethyl 3-methoxythiophene glyogyzalate.

Example 7 β-(
The reaction was carried out in the same manner as in Example 1 except that methyl 2-furyl)propionate was used, and a viscous liquid 5-2'-methoxycal was obtained as a product of 22.9 g of nylethyl 7-landariogideryl chloride. Yield 89.9%. The infrared absorption spectrum of this material was measured and 177
It was confirmed that the carbunyl bond of acid chloride exhibits strong absorption at 0α.

Next, the obtained 5-2/-methoxycargonylethylfurangliogyzalic acid chloride 22! Ethanol 100#I7 was slowly added to i under water cooling, and after stirring at room temperature for 3 hours, methanol was removed, and the residue was recrystallized from methanol to give pale yellow crystals 17.3 fi having the structure shown below.
I got it.

Melting point: 55-56°C Isolated yield (based on methyl β-(2-7lyl)propionate) 72.1% Elemental analysis values are C54,92%, H5,OOl and C11H4206 (240,22%) ), which was a calculated value of C55.00%, which agreed well with H5.04ch.

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'-methoxycardenylethylfurangliogidelic acid chloride.

Example 8 In a similar manner as described in detail in Example 1, a heteroaromatic compound and oxalyl halonide were prepared in the presence of hydrogen halide (hydrogen halide being the heteroaromatic compound 1).
0.01 to 10 mol), and the reaction was carried out 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 had a range of 1,760 to 1,780, and the acid fluoride had a range of 1,800 to 1,800.
Absorption based on carbonyl bond at 1880α and 1650
An absorption based on the carbonyl bond of the keto group at the α-position was observed at ~1700z. Based on this result and the mass spectrum measurement results, it was confirmed that the obtained compound was a heteroaromatic glyogideric 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.

Indicates the same halodane atom as X in .

Procedural amendment July 12, 1985. Day

Claims (1)

[Claims] In a method for producing heteroaromatic glyogyzalic acid halide by reacting a heteroaromatic compound and oxalyl halide, the heteroaromatic compound and oxalyl are reacted after or while introducing hydrogen halide into the liquid phase. A method for producing a heteroaromatic glyogyzalic acid halide, which comprises initiating a reaction with a halide.