JP2920212B1 - Method for producing 1,3-dioxolan-4-one compound - Google Patents

Abstract

An industrially advantageous method for producing a 1,3-dioxolan-4-one compound is provided. SOLUTION: The following general formula (1): (Wherein, R ¹ and R ² represent hydrogen or an organic group, Ar ¹ and Ar ^{2 each} represent an aryl group, and Ar ¹ and Ar ² may be bonded to each other) Dioxolan-4-
A method for producing an on-compound, the method comprising subjecting an α-hydroxycarboxylic acid compound and an arylthioketone compound to a desulfurization condensation reaction in the presence of a desulfurizing agent and a base.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a 1,3-dioxolan-4-one compound and a 1,3-dioxolan-4-one compound obtained by the method.

[0002]

2. Description of the Related Art Bull. Soc. Chem. Fr. , 1
970, 332, and 338 show compounds represented by the following formula (5).

Embedded image This compound is synthesized by reacting hydroxycarboxylic acid with diazoalkane (Ph) ₂ CN = N under light irradiation. However, in this method, synthesis of diazoalkane used as a reaction raw material is difficult. There is
Since the reaction conditions are severe and the yield of the target product is not good, it is unsatisfactory as an industrial method.

[0003]

SUMMARY OF THE INVENTION The present invention provides an industrially advantageous method for producing a 1,3-dioxolan-4-one compound and a novel 1,3-dioxolan-4-one obtained by the method. An object of the present invention is to provide a dioxolan-4-one compound.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have completed the present invention. That is, according to the present invention, the following general formula (1)

Embedded image (In the formula, R ¹ and R ² may be hydrogen, or may have a substituent.
Good alkyl, cycloalkyl, aryl, ant
Alkyl, pyridyl, thienyl, or furyl groups
An organic group selected from Ar ¹ and Ar ² represents an aryl group, and Ar ¹ and Ar ² may be bonded to each other) to produce a 1,3-dioxolan-4-one compound represented by the following formula: In the method, the following general formula (2)

Embedded image (Wherein R ¹ and R ² have the same meanings as described above) and the following general formula (3)

Embedded image (Wherein, Ar ¹ and Ar ² have the same meanings as described above), wherein the arylthioketone compound is subjected to a desulfurization condensation reaction in the presence of a desulfurizing agent and a base. You. Further, according to the present invention, the following general formula (1)

Embedded image (In the formula, R ¹ and R ² may be hydrogen, or may have a substituent.
Good alkyl, cycloalkyl, aryl, ant
Alkyl, pyridyl, thienyl, or furyl groups
And Ar ¹ and Ar ² represent an aryl group, and Ar ¹ and Ar ² may be bonded to each other.) Is done.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION In the above-mentioned general formula (1) showing a 1,3-dioxolan-4-one compound which is a target compound of the present invention, R ¹ and R ² represent hydrogen or an organic group. The organic group in such a case includes an aliphatic group, an aromatic group, and a heterocyclic group. The aliphatic group includes an alkyl group and a cycloalkyl group. The alkyl group has 1 to 1 carbon atoms.
2, preferably 1 to 6. These alkyl group and cycloalkyl group may have a substituent such as a halogen atom, an alkoxy group, a dialkylamino group, an acyl group, and an alkoxycarbonyl group. The alkyl group in these substituents can be a lower alkyl group having 1 to 6 carbon atoms. Illustrative examples of the aliphatic group include methyl, ethyl, propyl, butyl, hexyl, octyl,
Dodecyl, cyclohexyl, ethoxyethyl, dimethylaminoethyl, acetylethyl, methoxycarbonylethyl and the like. The aromatic group includes an aryl group and an arylalkyl group. These aryl group and arylalkyl group may have a substituent such as a halogen atom, an alkoxy group, a nitro group, an acyl group, a dialkylamino group, and an alkoxycarbonyl group. Specific examples of the aromatic group include phenyl, tolyl, xylyl, naphthyl, benzyl, phenethyl, naphthylmethyl, and their nucleus-substituted products. Examples of the heterocyclic group include a pyridyl group, a thienyl group, and a furyl group. These heterocyclic groups also include an alkyl group, a halogen atom,
It may have a substituent such as an alkoxy group, a nitro group, a dialkylamino group, an acyl group and an alkoxycarbonyl group. Ar ¹ and Ar ² in the general formula (1) each represent an aryl group. Examples of the aryl group include phenyl, tolyl, xylyl, naphthyl, and biphenyl. These aryl groups may have a substituent such as a halogen atom, an alkoxy group, a nitro group, a dialkylamino group, an acyl group, and an alkoxycarbonyl group. Ar ¹ and Ar ² may be bonded to each other via one atom or atomic group. In this case, a bonded body of Ar ¹ and Ar ² is represented by the following general formula (4). Condensed polycyclic groups.

Embedded image In the above formula, R ² and R ³ represent hydrogen or a substituent. In this case, the substituent may be any as long as it is inert to the reaction of the present invention. Such substituents include a chain or cyclic alkyl group, alkoxy group, dialkylamino group, acyl group, alkoxycarbonyl group, halogen atom, nitro group and the like. The alkyl group contained in these substituents usually has 1 to 6 carbon atoms. M and n are 1
And an integer of 1 to 4, usually an integer of 1 or 2. In the aforementioned-(X) t-, t represents 0 or 1. When t is 0,-(X) t- represents a mere joint (-), and when t is 1, it represents a divalent group -X-. In the divalent group X,
—O—, —S—, —N (R) — (R: alkyl group), lower alkylene group, lower alkenylene and the like are included. Specific examples of the condensed polycyclic group represented by the general formula (4) are shown below.

[0006]

Embedded image

According to the present invention, the 1,3-dioxolan-4-one compound is represented by the general formula (2):
It is produced by subjecting a hydroxy carboxylic acid compound and an aryl thioketone compound represented by the general formula (3) to a desulfurization condensation reaction. The desulfurization condensation reaction can proceed smoothly in the presence of a desulfurizing agent and a base. The desulfurizing agent may be any substance capable of forming a sulfide, and includes metals and metal compounds. Examples of the metal include Ag, Cu, Fe, Zn, and Pb. Examples of the metal compound include salts and oxides of metals such as Ag, Cu, Fe, Zn, and Pb, which easily form sulfides. The ratio of the desulfurizing agent used is the arylthioketone compound 1
The ratio is at least 1 equivalent, preferably 2 to 2.5 equivalents per equivalent. The base generates a carboxylate anion from the α-hydroxycarboxylic acid and acts as an acceptor for the cation H ⁺ generated as the reaction proceeds. As the base, any base can be used as long as it exhibits the above-mentioned action without hindering the above-mentioned desulfurization condensation reaction. Such substances include alkali metal salts, alkaline earth metal salts, tertiary amines, and the like, which are present in a liquid or solid state in the reaction system. As the alkali metal salt or alkaline earth metal salt,
Organic carboxylic acids, in particular, alkali metal salts and alkaline earth metal salts of hydroxycarboxylic acids are preferably used.
The proportion of the base used is α-hydroxycarboxylic acid compound 1
The ratio is at least 2 equivalents, preferably 3 to 4 equivalents per equivalent. The desulfurization condensation reaction is preferably carried out in the presence of a reaction solvent. In this case, examples of the reaction solvent include hydrocarbon solvents such as hexane, benzene, and toluene; chlorine solvents such as chloroform and dichloromethane;
Ethers such as HF and isopropyl ether, esters such as ethyl acetate, pyridine, acetonitrile, DMF
And other nitrogen-containing organic solvent systems. These organic solvents are used alone or in the form of a mixture.

In order to carry out the method of the present invention preferably, the arylthioketone compound 1 represented by the general formula (3)
The equivalent amount and about 1.2 equivalents of the α-hydroxycarboxylic acid compound represented by the general formula (2) are added to a reaction solvent and mixed to form a uniform solution. Next, a desulfurizing agent and a base are added to the solution, and stirring is continued at room temperature or under heating for several hours as necessary. The end of the reaction can be determined by using as a guide that the sulfide of the black metal usually precipitates and the reaction solution becomes transparent. Since the target substance is usually dissolved in a solution, an insoluble substance is separated by filtration and then poured into a large amount of water or a solvent is distilled off to obtain a crude product. The obtained crude product may be purified by recrystallization with an appropriate solvent such as isopropyl ether or ethyl acetate, or may be separated and purified by vacuum distillation, column chromatography or the like, if necessary.

Next, the compounds obtained by the present invention are shown below. (1) Compound (1)

Embedded image (2) Compound (2)

Embedded image (3) Compound (3)

Embedded image (4) Compound (4)

Embedded image

[0010]

Next, the present invention will be described in more detail by way of examples, but the present invention is not limited to these examples. In addition, 1, manufactured by the following example,
All 3-dioxolan-4-one compounds are novel compounds, and the results of elemental analysis, the results of nuclear magnetic resonance spectra of hydrogen and carbon, and the results of infrared absorption spectrum measurement were identified as main criteria. That is, from the nuclear magnetic resonance spectrum of the product, to determine the number of structures and hydrogen compounds from the integral value of the chemical shift and the signal in the infrared absorption spectrum, the hydroxy carboxylic acid of the raw material to 3000 cm ^-1 or more No absorption attributed to OH stretching vibration was observed, and strong absorption attributed to C ＝ O stretching vibration was observed around 1820 to 1780 cm ⁻¹ , confirming the skeleton structure.

Further, the produced compounds (1) to (4)
Corresponds to the compounds (1) to (4) shown above, and their physical property values represent the melting point (mp) and the solvent used for recrystallization in parentheses. Are shown in the order of nuclear magnetic resonance spectrum (H-NMR, C-NMR), infrared absorption spectrum (IR) and elemental analysis.

Example 1 Preparation of compound (1) Mandelic acid (dl-form) (182 mg) and 4,4'-bis (dimethylamino) thiobenzophenone (284 m
g) and a solution of triethylamine (360 mg) in acetonitrile (5 ml) were stirred while stirring and silver nitrate (420 mg) powder was added little by little. After stirring at room temperature for 3 hours, the reaction solution from which the insoluble silver sulfide was removed by filtration was developed on a silica gel column chromatography (developing solvent: a mixture of ethyl acetate and hexane at a ratio of 1: 1), and the desired product was collected. And recrystallized from isopropyl ether to obtain the compound (1). Yield 323 mg (80.5%); mp 108 ° C; H-N
MR (ppm) 2.97 (6H), 3.05 (6H),
5.21 (1H), 6.66-7.76 (13H); C
-NMR (ppm) 40.03, 72.65, 110.
61, 111.71, 111.88, 112.08, 1
26.00, 126.72, 127.19, 127.4
1,127.65,128.19,128.48,12
8.61,128.76,129.06,132.5
1,134.11, 138.36, 152.92; IR
(Cm ^-1 ) 1784,1603,1234,1176. C ₂₅ Elementary analysis as _{H 26 N 2 O 3 (%} ) measurements: C, 74.60; H, 6.51 ; N, 6.96. Calculated = C, 74.47; H, 6.50; N, 6.94.

Example 2 Preparation of Compound (2) α-Hydroxyisobutyric acid (125 mg) and xanthene-
When 9-thione (212 mg) was reacted in the same manner as in Example 1, compound (2) was obtained. Yield 247mg
(87.5%); mp114 ° C (isopropyl ether); H-NMR (ppm) 1.66 (6H), 7.2
7-7.65 (8H); C-NMR (ppm) 26.8
1,78.08,100.55,117.49,11
8.04, 120.73, 123.81, 123.9
8, 125.20, 125.81, 130.97, 13
4.91, 151.79, 176.07; IR (c
m- ¹ ) 2997, 1803, 1456, 1325, 11
82. Elementary analysis as _{C 17 H 14 O 4 (%} ) measurements = C, 72.33; H, 5.00 . Calculated: C, 72.25; H, 4.82.

Example 3 Preparation of Compound (3) When α-hydroxyisobutyric acid (125 mg) and thioxanthen-9-thione (228 mg) were reacted in the same manner as in Example 1, compound (3) was obtained. . Yield 250 mg (84%); mp 122 ° C. (methanol); H-NMR (ppm) 1.56 (6H), 7.2
6-7.84 (8H); C-NMR (ppm) 25.7
3,78.10,103.78,124.15,12
6.59, 127.27, 128.84, 133,2
8, 133.55, 175.40; IR (cm ^-1 ) 29
86, 1811, 1288, 1182. Elementary analysis as _{C 17 H 14 SO 3 (%} ) measurements: C, 68.44; H, 4.73 ; S, 10.75. Calculated: C, 68.61; H, 4.67; S, 10.96.

Example 4 Preparation of compound (4) (±) -2-hydroxyoctanoic acid (190 mg) and xanthene-9-thione (212 mg) were treated in the same manner as in Example 1 to obtain compound (4). Obtained. Yield 152 mg (45%); mp 88 ° C (isopropyl ether); H-NMR (ppm) 0.88 (3H);
1.31 to 1.56 (8H), 1.88 to 2.14 (2
H), 4.82 (0.5H), 4.85 (0.5H),
7.26 to 7.66 (8H); C-NMR (ppm) 1
3.90,22.39,25.23,28.69,3
1.41, 32.44, 75.40, 101.74, 1
17.05, 117.57, 119.18, 120.0
1,123.79,123.83,125.11,12
6.61, 131.15, 131.42, 151.1
2,151.77,173.02; IR (cm ^-1 ) 29
53, 2926, 1784, 1454, 1329, 12
34, 1204. Elemental analysis value (%) as C ₂₁ H ₂₂ O ₄ Measurement value: C, 74.72; H, 6.59. Calculated: C, 74.54; H, 6.56.

[0016]

The desulfurization-condensation reaction of the present invention proceeds very easily under mild conditions, and the 1,3-dioxolan-4-
The ON compound can be obtained with a high yield. Many α-hydroxycarboxylic acid compounds as raw materials used in the present invention are of biological origin. Therefore, according to the present invention, many optically active physiologically active compounds can be produced with high yield.
The compound of the present invention is also a compound having a structure in which the hydroxyl group and the carboxyl group of the α-hydroxycarboxylic acid compound are simultaneously protected, and by hydrolysis with an acid,
Return to the original α-hydroxycarboxylic acid compound. Therefore,
The compound of the present invention can be subjected to various reactions as a reaction raw material whose hydroxyl group and carboxyl group are simultaneously protected.

──────────────────────────────────────────────────続 き Continuation of front page (56) References Org. Chem. (1997), 62 (6), p. 1623-1629 (58) Fields investigated (Int. Cl. ⁶ , DB name) C07D 317/34 C07D 317/72 C07D 493/10 C07D 495/10 CAPLUS (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] [Claim 1] The following general formula (1) (In the formula, R ¹ and R ² may be hydrogen, or may have a substituent.
Good alkyl, cycloalkyl, aryl, ant
Alkyl, pyridyl, thienyl, or furyl groups
An organic group selected from Ar ¹ and Ar ² represents an aryl group, and Ar ¹ and Ar ² may be bonded to each other) to produce a 1,3-dioxolan-4-one compound represented by the following formula: In the method, the following general formula (2) is used. (Wherein R ¹ and R ² have the same meanings as described above) and the following general formula (3): (Wherein, Ar ¹ and Ar ² have the same meanings as described above), which is subjected to a desulfurization condensation reaction in the presence of a desulfurizing agent and a base. 2. The following general formula (1): (In the formula, R ¹ and R ² may be hydrogen, or may have a substituent.
Good alkyl, cycloalkyl, aryl, ant
Alkyl, pyridyl, thienyl, or furyl groups
Represents an organic group selected from Ar ¹ and Ar ² represents an aryl group, and Ar ¹ and Ar ² are bonded to each other.)
A 1,3-dioxolan-4-one compound represented by the formula: 3. The compound according to claim ² , wherein the conjugate of Ar ¹ and Ar ² is a condensed polycyclic group represented by the following general formula (4). Embedded image (Wherein R ² and R ³ represent hydrogen or a substituent, and m and p
Represents an integer of 1 to 4, and X represents -O-, -S-, -N (R)
-(R: alkyl group), lower alkylene group, lower alk
Represents a divalent group selected from nylene groups , and t is 0 or 1
Indicates)