JP4553104B2 - Process for producing carboxyphenylphosphonic acid monoester compound - Google Patents

Description

  The present invention relates to a carboxyphenylphosphonic acid ester compound and a method for producing the same.

  Dicarboxyphenylphosphonic acid compounds are phosphorus compounds with high polymerization reactivity, and are known to be incorporated in polyamides or polyesters to impart flame retardancy and heat resistance to these polymers (Patent Document 1: Special). (See Kaihei 11-106495, Patent Document 2: JP-A-11-286545). Further, as a production method thereof, a method of hydrolyzing a dialkyl compound of bis (alkoxycarbonyl) phenylphosphonate is known (see Patent Document 3: JP-A-11-193292).

  In recent years, various phosphorus compounds have been required to cope with the diversifying flame retardant and heat resistant polymer materials or other organic materials. In the carboxyphenylphosphonic acid ester compound, a carboxyphenylphosphonic acid dialkyl compound, a carboxyphenylphosphonic acid monoalkyl compound and an alkoxycarbonylphenylphosphonic acid monoalkyl compound are used as monomers for flame-retardant and heat-resistant polymer materials or other organic materials. Can be used as.

  Until now, as a method for producing a phenylphosphonic acid ester compound, a carboxyphenylphosphonic acid monoaryl ester compound (Non-patent Document 1: Journal of the Chemical Society, Perkin Transactions (J. Chem. Soc., Perkin Transactions), Vol. 1, No. 21, p. 2796-2803, 2001) and substituted phenylphosphonic acid monoalkyl ester compounds (Non-Patent Document 2: Journal of Heterocyclic Chemistry (J. Heterocyclic) Chem.,), Vol. 29, No. 4, p. 867-875 (1992)).

  However, methods for producing a dialkyl compound of carboxyphenylphosphonic acid, a monoalkyl compound of carboxyphenylphosphonic acid and a monoalkyl compound of alkoxycarbonylphenylphosphonic acid are not known.

Japanese Patent Laid-Open No. 11-106495 JP-A-11-286545 JP-A-11-286545 Journal of the Chemical Society, J. Chem. Soc., Perkin Transactions, Volume 1, No. 21, p. 2796-2803, 2001 Journal of Heterocyclic Chem., Vol. 29, No. 4, p. 867-875, 1992

  The present invention has been made in view of such circumstances, and is useful as a monomer for a flame-retardant and heat-resistant polymer material or as a raw material for other organic materials. It is an object of the present invention to provide an alkyl compound, an alkoxycarbonylphenylphosphonic acid monoalkyl compound, and a production method thereof.

（式中、Ｒ^１は炭素数１〜２０のアルキル基を表し、ｎは１〜２の整数を表す。）
で表されるカルボキシフェニルホスホン酸ジアルキルエステル化合物。
２． 式［２］

（式中、Ｒ^１は炭素数１〜２０のアルキル基を表し、ｎは１〜２の整数を表す。）
で表されるカルボキシフェニルホスホン酸モノアルキルエステル化合物。
３．式［３］

（式中、Ｒ^１及びＲ^３は炭素数１〜２０のアルキル基を表し、ｎは１〜２の整数を表す。）で表されるアルコキシカルボニルフェニルホスホン酸モノアルキルエステル化合物。
４．式［４］

（式中、Ｒ^１は炭素数１〜２０のアルキル基を表す。）
で表される１記載のジカルボキシフェニルホスホン酸ジアルキルエステル化合物。
５．式［５］

（式中、Ｒ^１は炭素数１〜２０のアルキル基を表す。）
で表される２記載のジカルボキシフェニルホスホン酸モノアルキルエステル化合物。
６．式［６］

（式中、Ｒ^１及びＲ^３は炭素数１〜２０のアルキル基を表す。）
で表される３記載のビス（アルコキシカルボニル）フェニルホスホン酸モノアルキルエステル化合物。
７．式［７］

（式中、Ｒ^１及びＲ^２は炭素数１〜２０のアルキル基を表し、ｎは１〜２の整数を表す。）で表されるアルコキシカルボニルフェニルホスホン酸ジアルキルエステル化合物を、アルカリ金属炭酸塩化合物、アルカリ金属リン酸塩化合物、アルカリ土金属炭酸塩化合物、アルカリ土金属水酸化物、アルカリ土金属リン酸塩化合物及び有機塩基の一種以上を用いて加水分解することを特徴とする式［１］

（式中、Ｒ^１は炭素数１〜２０のアルキル基を表し、ｎは１〜２の整数を表す。）
で表されるカルボキシフェニルホスホン酸ジアルキルエステル化合物の製造法。
８．式［７］

（式中、Ｒ^１及びＲ^２は炭素数１〜２０のアルキル基を表し、ｎは１〜２の整数を表す。）で表されるアルコキシカルボニルフェニルホスホン酸ジアルキルエステル化合物を、アルカリ金属水酸化物で加水分解することを特徴とする式［２］

（式中、Ｒ^１は炭素数１〜１０のアルキルを表し、ｎは１〜２の整数を表す。）
で表されるカルボキシフェニルホスホン酸モノアルキルエステル化合物の製造法。
９．式［２］

（式中、Ｒ^１は炭素数１〜１０のアルキル基を表し、ｎは１〜２の整数を表す。）
で表されるカルボキシフェニルホスホン酸モノアルキルエステル化合物を、式［８］

（式中、Ｒ^３は炭素数１〜２０のアルキル基を表す。）
で表されるアルキルアルコールと酸触媒下反応させることを特徴とする、式［３］

（式中、Ｒ^１及びＲ^３は炭素数１〜２０のアルキル基を表し、ｎは１〜２の整数を表す。）で表されるアルコキシカルボニルフェニルホスホン酸モノアルキルエステル化合物の製造法。 The inventors of the present invention have completed the present invention as a result of intensive studies in order to achieve the above object.
That is, the present invention
1. Formula [1]

(In the formula, R ¹ represents an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2).
A carboxyphenylphosphonic acid dialkyl ester compound represented by:
2. Formula [2]

(In the formula, R ¹ represents an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2).
A carboxyphenylphosphonic acid monoalkyl ester compound represented by:
3. Formula [3]

(Wherein, R ¹ and R ³ represents an alkyl group having 1 to 20 carbon atoms, n is an integer of 1-2.) Alkoxycarbonyl phenylphosphonic acid represented by the monoalkyl ester compound.
4). Formula [4]

(In the formula, R ¹ represents an alkyl group having 1 to 20 carbon atoms.)
The dicarboxyphenylphosphonic acid dialkyl ester compound according to 1, which is represented by:
5). Formula [5]

(In the formula, R ¹ represents an alkyl group having 1 to 20 carbon atoms.)
The dicarboxyphenylphosphonic acid monoalkyl ester compound of 2 represented by these.
6). Formula [6]

(In the formula, R ¹ and R ³ represent an alkyl group having 1 to 20 carbon atoms.)
3. The bis (alkoxycarbonyl) phenylphosphonic acid monoalkyl ester compound according to 3, represented by:
7). Formula [7]

(Wherein R ¹ and R ² represent an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2), an alkoxycarbonylphenylphosphonic acid dialkyl ester compound represented by an alkali metal carbonate Hydrolysis using one or more of compounds, alkali metal phosphate compounds, alkaline earth metal carbonate compounds, alkaline earth metal hydroxides, alkaline earth metal phosphate compounds and organic bases [1 ]

(In the formula, R ¹ represents an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2).
The manufacturing method of the carboxyphenylphosphonic acid dialkyl ester compound represented by these.
8). Formula [7]

(Wherein R ¹ and R ² represent an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2), an alkoxycarbonylphenylphosphonic acid dialkyl ester compound represented by alkali metal hydroxide Formula [2] characterized by hydrolysis with a product

(In the formula, R ¹ represents an alkyl having 1 to 10 carbon atoms, and n represents an integer of 1 to 2).
The manufacturing method of the carboxyphenylphosphonic acid monoalkylester compound represented by these.
9. Formula [2]

(In the formula, R ¹ represents an alkyl group having 1 to 10 carbon atoms, and n represents an integer of 1 to 2).
A carboxyphenylphosphonic acid monoalkyl ester compound represented by the formula:

(In the formula, R ³ represents an alkyl group having 1 to 20 carbon atoms.)
The reaction is carried out in the presence of an acid catalyst with an alkyl alcohol represented by the formula [3]

(Wherein R ¹ and R ³ represent an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2). A method for producing an alkoxycarbonylphenylphosphonic acid monoalkyl ester compound represented by

The dialkyl compound of carboxyphenylphosphonic acid, the monoalkyl compound of carboxyphenylphosphonic acid and the monoalkyl compound of alkoxycarbonylphenylphosphonic acid of the present invention are made of a polymer material such as flame retardant and heat resistant polyester, polyamide, and epoxy thermosetting resin. It is useful as a raw material for monomers and other organic materials.
Further, by using the production method of the present invention, a carboxyphenylphosphonic acid dialkyl compound, a carboxyphenylphosphonic acid monoalkyl compound and an alkoxycarbonylphenylphosphonic acid monoalkyl compound can be obtained in high yield.

The present invention will be described in detail below.
The compound of the present invention is represented by the above formulas [1] to [6]. Here, n is 1 to 2, and n is preferably 2 in consideration of application of the polymer material to the monomer and other organic materials. Further, preferably, those represented by the above formulas [4], [5] and [6].

In each of the above formulas, the alkyl group having 1 to 20 carbon atoms may be linear, branched or cyclic. For example, methyl, ethyl, n-propyl, i-propyl, c-propyl, n-butyl , I-butyl, t-butyl, c-butyl, s-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n -Tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, 2-ethylpropyl, 2,2-dimethylpropyl, 1,2-dimethylpropyl, 1,1,2-trimethylpropyl 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylbutyl, 1,2 -Dimethylbutyl, 1,3-dimethylbutyl, 2,2- Methylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, c-hexyl, 1- Examples include methyl-c-pentyl, 1-ethyl-c-butyl and 1,2-dimethyl-c-butyl.
In the above, n represents normal, i represents iso, s represents secondary, c represents cyclo, and t represents tertiary.

  The production method of the compound of the present invention is represented by the following three reaction schemes as described above.

^(Wherein, _R 1, ^{R 2} and ^{R 3} represents an alkyl group having 1 to 20 carbon atoms, n is an integer of 1-2.)
Here, although not particularly limited, a case where n is 2 and the substituent of the benzene ring is in the 3rd and 5th positions will be described.

This will be described in order from scheme (1) below.
First, a method for producing a 3,5-bis (alkoxycarbonyl) phenylphosphonic acid dialkyl ester compound as a raw material is represented by the following reaction scheme described in JP-A-11-193292.

(In the formula, R ¹ and R ² represent an alkyl group having 1 to 20 carbon atoms.)
That is, the desired product can be obtained in high yield from 3,5-bis (alkoxycarbonyl) phenyl bromide and trialkyl phosphite using a metal catalyst.

Specifically, dimethyl 3,5-bis (methoxycarbonyl) phenylphosphonate, diethyl 3,5-bis (methoxycarbonyl) phenylphosphonate, dipropyl 3,5-bis (methoxycarbonyl) phenylphosphonate, 3,5 -Dibutyl bis (methoxycarbonyl) phenylphosphonate, didecyl 3,5-bis (methoxycarbonyl) phenylphosphonate, dieicosyl 3,5-bis (methoxycarbonyl) phenylphosphonate, 3,5-bis (ethoxycarbonyl) phenylphosphone Dimethyl 3,5-bis (ethoxycarbonyl) phenylphosphonate, dipropyl 3,5-bis (ethoxycarbonyl) phenylphosphonate, dibutyl 3,5-bis (ethoxycarbonyl) phenylphosphonate, 3,5-bis (Ethoxycal Nyl) didecyl phenylphosphonate, dieicosyl 3,5-bis (ethoxycarbonyl) phenylphosphonate, dimethyl 3,5-bis (propoxycarbonyl) phenylphosphonate, diethyl 3,5-bis (propoxycarbonyl) phenylphosphonate, 3, , 5-bis (propoxycarbonyl) phenylphosphonate dipropyl, 3,5-bis (propoxycarbonyl) phenylphosphonate dibutyl, 3,5-bis (propoxycarbonyl) phenylphosphonate didecyl, 3,5-bis (propoxycarbonyl) Diaecosyl phenylphosphonate, dimethyl 3,5-bis (butoxycarbonyl) phenylphosphonate, diethyl 3,5-bis (butoxycarbonyl) phenylphosphonate, 3,5-bis (butoxycarbonyl) phenylphosphone Dipropyl, 3,5-bis (butoxycarbonyl) phenylphosphonate dibutyl, 3,5-bis (butoxycarbonyl) phenylphosphonate didecyl, 3,5-bis (butoxycarbonyl) phenylphosphonate dieicosyl, 3,5-bis ( Dimethyl butoxycarbonyl) phenylphosphonate, diethyl 3,5-bis (butoxycarbonyl) phenylphosphonate, diprotyl 3,5-bis (butoxycarbonyl) phenylphosphonate, dibutyl 3,5-bis (butoxycarbonyl) phenylphosphonate, Didecyl 3,5-bis (butoxycarbonyl) phenylphosphonate, dieicosyl 3,5-bis (butoxycarbonyl) phenylphosphonate, dimethyl 3,5-bis (decaoxycarbonyl) phenylphosphonate, 3,5-bis (decaoxy) Dicarbonyl) phenylphosphonate, 3,5-bis (decaoxycarbonyl) phenyl phosphonate dipropyl, 3,5-bis (decaoxycarbonyl) phenylphosphonate dibutyl, 3,5-bis (decaoxycarbonyl) phenylphosphone Didecyl acid, dieicosyl 3,5-bis (decaoxycarbonyl) phenylphosphonate, dimethyl 3,5-bis (eicosyloxycarbonyl) phenylphosphonate, diethyl 3,5-bis (docosaoxycarbonyl) phenylphosphonate, 3, , 5-bis (eicosyloxycarbonyl) phenylphosphonate dipropyl, 3,5-bis (eicosyloxycarbonyl) phenylphosphonate dibutyl, 3,5-bis (eicosyloxycarbonyl) phenylphosphonate didecyl, 3,5 -Screw ( Icosyl oxycarbonyl) dieicosyl and phenyl phosphonic acid. From the standpoint of availability of raw materials and reactivity, compounds in which R ¹ and R ² are methyl groups or ethyl groups are preferred.

The type of base required for hydrolysis is important in the present invention. Base 1 is an alkali metal carbonate compound, an alkaline earth metal carbonate compound, an alkaline earth metal hydroxide, an alkali metal phosphate compound, an alkaline earth metal phosphate compound, and an organic base.

Specific examples include lithium carbonate, sodium carbonate, potassium carbonate, magnesium carbonate, calcium carbonate, barium carbonate, lithium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, magnesium hydrogen carbonate, calcium hydrogen carbonate and barium hydrogen carbonate. Alkali metal carbonate compounds and alkaline earth metal carbonate compounds. Alkaline earth metal hydroxides typified by magnesium hydroxide, calcium hydroxide, strontium hydroxide and barium hydroxide. Lithium phosphate, sodium phosphate, potassium phosphate, magnesium phosphate, calcium phosphate, barium phosphate, lithium monohydrogen phosphate, sodium monohydrogen phosphate, potassium monohydrogen phosphate, magnesium monohydrogen phosphate, calcium monohydrogen phosphate, barium monohydrogen phosphate, dihydrogen phosphate Alkali metal phosphate compounds and alkaline earth metal phosphate compounds represented by lithium hydrogen, sodium dihydrogen phosphate, potassium dihydrogen phosphate, magnesium dihydrogen phosphate, calcium dihydrogen phosphate, barium dihydrogen phosphate, and the like;
Furthermore, organic bases such as aliphatic amines and aromatic amines represented by triethylamine, triethylamine, pyridine, 4- (dimethylamino) pyridine and the like can be mentioned.

Among these, sodium carbonate and potassium carbonate are preferred from the viewpoint of the yield and economical efficiency of the target product. These can also be used individually or in mixture of 2 or more types.
The amount used is preferably 2 to 5 equivalents relative to the substrate, and particularly 2 to 3 equivalents gives the desired product in high yield.

Moreover, water and alcohols are preferable as the solvent. The amount of water used is preferably 2 to 50 times, more preferably 2 to 5 times, the substrate. As the alcohol, an aliphatic chain primary or secondary alcohol having 1 to 10 carbon atoms is preferable. Specifically, it is preferable to use the same alkyl alcohol as the alkyl group of the phosphate group of the substrate. For example, when the substrate is dimethyl 3,5-bis (methoxycarbonyl) phenylphosphonate, methanol is preferable, and when the substrate is diethyl 3,5-bis (methoxycarbonyl) phenylphosphonate, ethanol is preferable. The amount used is preferably 2 to 50 times by mass, and particularly preferably 2 to 10 times by mass with respect to the substrate.

  The reaction temperature is preferably 0 to 200 ° C, and particularly preferably 50 to 150 ° C. The reaction time depends on the reaction temperature, but is usually completed in 2 to 24 hours.

After completion of the reaction, the solvent is distilled off, water is added, and then an aqueous hydrochloric acid solution is added dropwise to make the solution acidic. The resulting crystals are filtered or made acidic and then extracted with ethyl acetate, methyl isobutyl ketone (MIBK) or the like. And then concentrating to obtain the desired product. Further, it can be purified by recrystallization if necessary.

  Next, a method for producing a 3,5-dicarboxyphenylphosphonic acid monoalkyl ester compound by hydrolysis of the 3,5-bis (alkoxycarbonyl) phenylphosphonic acid dialkyl ester compound of Scheme (2) will be described.

The base 2 is an alkali metal hydroxide, specifically, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, and the like. Particularly preferred are sodium hydroxide and potassium hydroxide.
The amount used is preferably 3 to 10 equivalents relative to the substrate, and particularly 3 to 6 equivalents gives the desired product in high yield.

Moreover, as a solvent, water and alcohol are preferable. The amount of water used is preferably 2 to 50 times, more preferably 2 to 5 times, the substrate. As the alcohol, an aliphatic chain primary or secondary alcohol having 1 to 10 carbon atoms is preferable. Specifically, it is preferable to use the same alkyl alcohol as the alkyl group of the phosphate group of the substrate. For example, when the substrate is dimethyl 3,5-bis (methoxycarbonyl) phenylphosphonate, methanol is preferable, and when the substrate is diethyl 3,5-bis (methoxycarbonyl) phenylphosphonate, ethanol is preferable. The amount used is preferably 2 to 50 times by mass, and particularly preferably 2 to 10 times by mass with respect to the substrate.

  The reaction temperature is preferably 0 to 200 ° C, and particularly preferably 50 to 150 ° C. The reaction time depends on the reaction temperature, but is usually completed in 2 to 24 hours.

After completion of the reaction, the solvent is distilled off, water is added and then an aqueous hydrochloric acid solution is added dropwise to make the solution acidic. The resulting crystals are filtered or made acidic and then ethyl acetate, methyl isobutyl ketone (MIBK) or the like. Extraction and concentration yields the desired product. Further, it can be purified by recrystallization if necessary.

Next, scheme 3 will be described.
The 3,5-dicarboxyphenylphosphonic acid monoalkyl ester obtained in Scheme 2 is esterified with an alkyl alcohol in the presence of an acid catalyst to give 3,5-bis (alkoxycarbonyl) phenylphosphonic acid monoalkyl ester. is there.

Examples of the alkyl alcohol include primary or secondary alkyl alcohols having 1 to 20 carbon atoms. Specific examples include primary or secondary alcohols such as methanol, ethanol, propanol, butanol, amyl alcohol, hexanol, heptanol, octanol, nonanol, decanol, and eicosanol. In particular, methanol and ethanol are preferable. The amount used is preferably 1 to 50 times by mass, and particularly preferably 2 to 10 times by mass with respect to the substrate.

As the acid catalyst, inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid are preferable, and sulfuric acid is particularly preferable. The amount used is preferably 0.01 to 50% by mass, particularly 1 to 30% by mass, based on the substrate.

The reaction temperature can be 0 ° C. to 200 ° C., but the reaction is particularly preferably carried out at the boiling point of alcohols of 50 to 180 ° C.
The reaction time can be determined from the analysis result of the reaction solution such as liquid chromatography, and can usually be completed in 1 to 30 hours.

After completion of the reaction, the residual alcohols are distilled off by concentration, and the residue is extracted with ethyl acetate, methyl isobutyl ketone (MIBK), toluene or the like and then concentrated to obtain the desired product. Further, it can be purified by recrystallization or column chromatography if necessary.
The reaction and purification of the present invention described above can be performed batchwise or continuously.
The reaction can be carried out at normal pressure or at elevated pressure.

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.
The analytical methods used in the examples are as follows.
[1] [Gas chromatography (GC)]
Model: Shimadzu GC-17A, Column: Capillary column CBP1-W25-100 (25 mx 0.53 mm φx 1μm), Column temperature: 100 ℃ (holding 2 min.)-8 ℃ / min. (Raising rate) -290 ℃ (Holding 10 min.), Inlet temperature: 290 ° C, detector temperature: 290 ° C, carrier gas: helium, detection method: FID method.
[2] [Mass Spectrometry (MASS)]
Model: LX-1000 (JEOL Ltd.), Detection method: FAB method.
[3] [ ¹ H NMR]
Model: INOVA500 (VARIAN Corp.), Measuring solvent: DMSO-d ₆
[4] [ ¹³ C NMR]
Model: INOVA500 (VARIAN Corp.), Measuring solvent: DMSO-d ₆
[5] [Melting point (mp)]
Measuring instrument: Automatic melting point measuring device, FP62 (METTLER TOLEDO)
[6] [Liquid chromatography (LC)]
Model: Shimadzu LC-10A, Column: YMC-Pack ODS-AM (S-5μm, 120A, AM-303, AM12S05-2546WT) (250 mm x 4.6 mm φ), Column temperature: 40 ℃, Detector wavelength: UV 230 nm, eluent: H ₂ O / CH ₃ CN = 1/2, flow rate: 0.5 ml / min.

Example 1

In a 300 mL glass four-necked reaction flask, 16.50 g (50.0 mmol) of diethyl 3,5-bis (methoxycarbonyl) phenylphosphonate (DE3,5-BMPP), 116 g of ethanol, 17.3 g (125 mmol) of potassium carbonate and water 52 g was charged and refluxed at an internal temperature of 75 ° C. (oil bath 100 ° C.) for 7 hours. After concentration, ethyl acetate and water were added, hydrochloric acid was added dropwise to make the solution acidic, and the organic layer was separated. After further washing with water and concentration, 12.1 g (yield 80.1%) of white crystals were obtained. When this crystal was analyzed by LC, the raw material DE3,5-BMPP disappeared and a new single peak appeared.
This product was confirmed to be diethyl 3,5-dicarboxyphenylphosphonate (DE3,5-DCPP) from the following results.

^{MASS (FAB -, m / e} (%)): 301 ([MH] -, 100), 257 (36), 153 (40).
¹ H NMR (DMSO-d ₆ , δppm): 1.23 (t, J = 7.03Hz, 6H), 4.03-4.09 (m, 4H), 8.39 (dd, J ₁ = 1.83Hz, J ₂ = 13.19Hz, 2H ), 8.62 (d, J = 0.61Hz, 1H), 13.6 (brs, 2H).
¹³ C NMR (DMSO-d ₆ , δppm): 16.1472, 16.1929, 62.3323, 62.3858, 129.3401 (0.5), 130.8433 (0.5), 131.9344, 132.0488, 133.3994, 135.4671, 135.5511, 165.7282 (2) .
mp. (℃): 214-215

Examples 2-13

  A 50 mL glass four-necked reaction flask was charged with 0.99 g (3.0 mmol) of DE3,5-BMPP, 10 g of ethanol, 5 g of base and water, and refluxed at an internal temperature of 75 ° C. (oil bath 100 ° C.) for 7 hours. After concentration, ethyl acetate and water were added, hydrochloric acid was added dropwise to make the solution acidic, and the organic layer was separated. After further washing with water and concentration, white crystals were obtained. The purity of this crystal was measured by LC analysis, and the yield of DE3,5-DCPP was calculated. The results are shown below.

Table 1 Effect of base on DE3,5-DCPP production

Example 14

A 300 mL glass four-necked reaction flask was charged with 16.5 g (50 mmol) of diethyl DE3,5-BMPP, 83 g of ethanol, 9.0 g (225 mmol) of sodium hydroxide and 27 g of water, and an internal temperature of 75 ° C. (oil bath 100 ° C.). Refluxed for 18 hours. After concentration, ethyl acetate and water were added, and hydrochloric acid was added dropwise to make the solution acidic. The precipitated crystals were separated by filtration, washed with ethyl acetate and water, and dried to give 13.3 g of white crystals (yield 97.1). %)was gotten. When this crystal was analyzed by LC, the raw material DE3,5-BMPP disappeared and a new single peak appeared.
This product was confirmed to be ethyl 3,5-dicarboxyphenylphosphonate (E3,5-DCPP) from the following results.

^{MASS (FAB -, m / e} (%)): 273 ([MH] -, 100), 229 (54).
¹ H NMR (DMSO-d ₆ , δppm): 1.03 (t, J = 7.03Hz, 3H), 3.61-3.67 (m, 2H), 8.43 (s, 1H), 8.49 (dd, J ₁ = 1.53Hz, J ₂ = 11.61Hz, 2H), 13.60 (brs, 3H).
¹³ C NMR (DMSO-d ₆ , δppm): 16.5820 (for 0.5), 16.6354 (for 0.5), 59.0894, 130.5227 (for 1.5), 131.0110 (for 1), 131.1102 (for 1.5), 135.8180 , 135.8943, 166.8192 (for 2 bottles).
mp. (℃): 234-235

Examples 15-17

  A 50 mL glass four-necked reaction flask was charged with 0.99 g (3.0 mmol) of DE3,5-BMPP, 10 g of ethanol, 5 g of base and water, and refluxed at an internal temperature of 75 ° C. (oil bath 100 ° C.) for 7 hours. After concentration, ethyl acetate and water were added, hydrochloric acid was added dropwise to make the solution acidic, and the organic layer was separated. After further washing with water and concentration, white crystals were obtained. The purity of this crystal was measured by LC analysis, and the yield of E3,5-DCPP was calculated. The results are shown below.

Table 2 Effect of base on E3,5-DCPP formation

Example 18

A 300 mL glass four-necked reaction flask was charged with 11.4 g (41.5 mmol) of E3,5-DCPP, 93 g of ethanol and 2.0 g of 98% concentrated sulfuric acid, and refluxed at an internal temperature of 75 ° C. (oil bath 100 ° C.) for 30 hours. . After standing overnight at room temperature, insoluble crystals were filtered off, and the obtained filtrate was concentrated and dried to obtain white crystals. The residue was dissolved by adding ethyl acetate and water, and the organic layer was separated, further washed with water 4 times, and concentrated to give 12.2 g of white crystals having a single peak by LC (yield 89.1%). )was gotten. Further, after heating and dissolving in ethyl acetate / water = 1/1, when the solution is concentrated, crystals start to precipitate. After cooling with ice, the crystals are filtered and dried to yield 11.5 g of white crystals (yield 83.9 %)was gotten. This crystal was confirmed to be ethyl 3,5-bis (ethoxycarbonyl) phenylphosphonate (E3,5-BEPP) from the following results.

MASS (FAB ⁺ , m / e (%)): 331 ([M + H] ⁺ , 100), 303 (33).
¹ H NMR (DMSO-d ₆ , δppm): 1.35 (t, J = 7.03Hz, 3H), 1.44 (t, J = 7.18Hz, 6H), 4.14-4.20 (m, 2H), 4.44 (dd, J ₁ = 7.18Hz, J ₂ = 14.21Hz, 4H), 8.64 (dd, J ₁ = 1.53Hz, J ₂ = 13.75Hz, 2H), 8.82 (dd, J ₁ = 1.68Hz, J ₂ = 2.60Hz, 1H ), 12.27 (brs, 1H).
¹³ C NMR (DMSO-d ₆ , δppm): 14.1099 (for 2), 16.0022 (for 0.5), 16.0556 (for 0.5), 61.5999 (for 2), 62.5307 (for 0.5), 62.5765 (0.5) 130.8204, 131.1256, 131.2477, 133.9106, 136.0776, 136.5354, 164.6753, 168.6430.
mp. (℃): 111-112

Claims (2)

Formula [7]

(In the formula, R ¹ and R ² represent an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2).
A dialkyl ester compound represented by formula (2) is hydrolyzed with an alkali metal hydroxide at 50 to 150 ° C. [2]

(In the formula, R ¹ represents an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2).
The manufacturing method of the carboxyphenylphosphonic acid monoalkylester compound represented by these. Formula [7]

(In the formula, R ¹ and R ² represent an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2).
The alkoxycarbonylphenylphosphonic acid dialkyl ester compound represented by formula (2) is hydrolyzed with an alkali metal hydroxide at 50 to 150 ° C. , and the formula [2]

(In the formula, R ¹ represents an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2).
A carboxyphenylphosphonic acid monoalkyl ester compound represented by the formula [2] was obtained, and the resulting compound represented by the formula [2]

(In the formula, R ³ represents an alkyl group having 1 to 20 carbon atoms.)
The reaction is carried out in the presence of an acid catalyst with an alkyl alcohol represented by the formula [3]

(In the formula, R ¹ and R ³ represent an alkyl group having 1 to 20 carbon atoms, and n represents an integer of 1 to 2)
The manufacturing method of the alkoxycarbonylphenylphosphonic acid monoalkylester compound represented by these.