JPS61277676A - Production of quinoylfuran - Google Patents

Abstract

PURPOSE:To obtain the titled compound, containing a novel compound of the same system as the naturally occurring compound and having antimicrobial activity in a large amount by the chemical synthetic method in one stage, by oxidizing 2-(2-hydroxyphenyl)-2,5-dihydrofuran with a specific oxidizing agent. CONSTITUTION:A 2-(2-hydroxyphenyl)-2,5-dihydrofuran (in which 4-methyl substitution product thereof is a well-known compound) is reacted with n-butyl lithium and converted into a metal salt, e.g. lithium salt, to increase the solubility in water. The resultant metal salt then oxidized with an oxidizing agent, e.g. an aqueous solution of potassium nitrosodisulfonate (called Fremy's salt) to afford the aimed compound, capable of existing stably at <=0 deg.C in N2 though decomposed by allowing to stand at room temperature and useful as a medicine, e.g. 2-quinoyl-4-(4-methyl-3-pentenyl)furan, particularly a 2-quinoyl-4-substituted furan. EFFECT:The raw material can also be readily synthesized.

Description

Detailed Description of the Invention [Industrial Field of Application] The present invention provides 2-quinoylfurans, particularly 2-quinoyl-
The present invention relates to a novel method for producing 4-substituted furans.

[Conventional technology]

Conventionally, a substance called echinofuran, which is represented by the following formula I, has been isolated as a pigment component from a chloroform extract of tissue cultured cells of a plant belonging to the family Murasaceae [Japanese Society 99th Anniversary Lecture Abstracts Collection, p. 206 ( 197
9)].

However, the above-mentioned echinofuran is only contained in trace amounts (approximately 3%) in natural purple violet and its tissue culture cells, and is an unstable substance, so it is inconvenient to conduct research on its pharmacological effects. I failed.

On the other hand, as a conventional method for synthesizing 2-quinoyl-5-methylfuran, p-quinone and 2-methylfuran are reacted to obtain 2-(2,5-dihydroxyphenyl)-5-methylfuran. A method of obtaining 2-quinoyl-5-methylfuran by t-R reaction is known [Herpetica chimica acta (He1v, C!him, Acta,
), page 1974 (1966)].

[One point while the invention is trying to solve the problem]

However, the above synthesis method is not satisfactory because the synthesis of methylfurans is troublesome, and when 3-substituted furan is used as a raw material, there is a risk that substituted products at the 3- and 4-positions of 2-quinoylfuran will be produced. It cannot be said that it is a suitable synthesis method.

A first object of the present invention is to provide a novel method for producing 2-quinoylfurans. A second object is to provide a method for producing a novel compound of the same family as echinofuran represented by the above formula I.

[Means for solving problems]

To summarize the present invention, the present invention provides 2-quinoylfuran k
The invention relates to a method for producing m, and is characterized in that 2-(2-hydroxyphenyl)-2,5-dihydrofuran is oxidized with potassium nitrosodisulfonate.

- If the reaction in the present invention is shown by a structural formula using 2-quinoylfuran as an example, it is as follows.

4 of the dihydrofurans as raw materials in the method of the present invention
The -methyl substituted product is a known compound [Journal Op the Chemical Society, Chemical Communication (J.

C! ham, Soa, Oh, em Oomm,)
See WJ p. 458 (1979)]. Other compounds were prepared by adding dimethylsulfonium methylide cH*=5( aH
3) can be synthesized by reacting, preferably in the presence of a tertiary amine. Furthermore, the compound of the general formula (■) is obtained by aldol condensation of a compound represented by the general formula (H,0-O0-R (in the formula, R has the same meaning as the formula (■)) and salicylaldehyde in the presence of a basic catalyst. It can be synthesized by

Potassium nitrosodisulfonate, which is an oxidizing agent used in the method of the present invention, is a compound known as the 7-Remy salt that oxidizes phenol to quinone [Chem, Rev., Vol. 71]. 229
(1971)] However, when the reaction conditions of the method of the present invention were examined, it was found that even though the starting material dihydrofuran was used in its free form, it was changed to a metal salt to increase its solubility in water.
It has been found that the reaction rate and yield are increased by reacting with an aqueous solution of 7 Remy salt. Examples of metal salts include lithium salts obtained by reaction with n-butyllithium.

Among the objects of the method of the present invention are the above formulas! Also includes compounds of the same family as the compound represented by. Among them are the formulas ■
Similar to the compound described above, there are also compounds that are unstable when left at room temperature in a sudden atmosphere. However, some of these compounds, such as 2-quinoyl-4-(4-methyl-3-pentenyl)furan, can be separated in large quantities by thin layer chromatography using a silica gel carrier under a nitrogen atmosphere. Furthermore, they found that it can be stably stored in nitrogen at temperatures below 0°C.

〔Example〕

The present invention will be explained in more detail below using all Examples and Reference Examples, but the present invention is not limited to these Examples.

Example 1 2-(2-hydroxyphenyl)-4-methyl-2,5-dihydrofuran 500 m in SOtd branched ampoule tube
? (2,87 mmol) and tetrahydro7ran 10-
and cooled to -30°C in a dry ice-acetone bath. n-BuLi (15 thihexane solution) 1.8d (2
, 90 mmol) 1 and left at 0°C for 20 minutes. The lithium salt obtained by distilling off the solvent under vacuum is mixed with water at 30%
- dissolved in

Next, the 300 was equipped with a stirrer, thermometer, and dropping funnel.
d.Fremy salt 59F (146 mmol) and 200 sgt of a 1% NaHCO aqueous solution were added to a Mitsuro flask to form a homogeneous solution, and further n-hexane 100 was added. The aqueous solution of lithium salt prepared above was added dropwise into this solution for 20 minutes.
Stir vigorously for 2.0 hours at ℃. The reaction solution was separated, the aqueous layer was extracted twice with hexane, the hexane layers were combined, washed with water, and then dried over anhydrous MgSO4. Mg80. P was separated and hexane was distilled off under reduced pressure at a temperature of 0° C. or lower to obtain 121 mf of almost pure 2-quinoyl-4-methylfuran as yellow crystals (yield 22%).

N, M, R, (CD0L, )δppm: 2.08 (
5H, 8), &48(IH,Sun, 6.50(IH
,Day).

7.05 (IH, 8), 7.72 (2H, B).

X, R1(0HOz, )crn-1:2980, 29
50.167B, 1664.1645°1605, 1
578.1295.11 Do, 928.905゜Example 2 2-(2-human roxyphenyl)-4-C4-mef-3-pentenyl)-2,5- in a 20-Eggplant flask
Add 1.0 f (4.35 mmol) of dihydrofuran and 5 g of tetrahydrofuran, and add n-butyllithium hexa/solution (27 wt%) 1.139 (4,
79 mmol) was added and stirred for 5 minutes.

Thereafter, the solvent was distilled off to obtain a compatible lithium salt. Furthermore, it is equipped with a stirrer, a thermometer, and a cooler.
A solution of the above-mentioned lithium salt dissolved in 100-g of water was added to a Tulo flask, and then a solution of 5.0 f (1a 7 mmol) of Flemy's salt dissolved in 1% NaH 00 g was added at 18°C, and the mixture was further stirred at the same temperature for 40 hours. Just in case.

After sowing, extract twice with 100% ether and remove under reduced pressure.
Ether was distilled off at 0°C to obtain a brown solid of 1.02F. When the product was fractionated under a nitrogen stream using a solvent of hexane/acetone = 5/1 (volume ratio) and a silica gel disk (3 exposures), it was found that 2-quinoyl-4
-(4-methyl-3-pentenyl]furan is 109my
2-quinoyl-a-(a-
Methyl-3-pentenyl)-2,5-dihydrofuran f
70 mW was obtained. In addition, unreacted raw material i552mF was recovered. The above target compound is a bright yellow solid, and like the compound of formula I, it gradually decomposes and turns reddish-brown when left at room temperature, but it can be stably stored in nitrogen at temperatures below 0°C. I found it. Well, this compound has antibacterial activity and is useful as a medicine.

02-quinoyl-4-(4-methyl-5-pentenyl)
Furan N0M, R, (C!DO4,) δppm: 1.60 (
3HS, le 1゜70 (5HS, n, ≦:, 40~
2.60 (4Hm, ), 5.16 (IHt, J=7
Hz).

6.74 (1B,), &76 (IH8,), 7.0
2 (IH8,), 7.56 (2HS,) Engineering, R, (CHC43cm-”: 2960, 2920.2B60.1670.165B.

1640, 1600.1570.1456.1285°1o? o, 922.904.852゜maaa m/
e: zs6 (M+), 240, 190, 188, 187, 1
37°160, 69.42°O intermediate 2-quinoyl-4-(4-methyl-5-
pentenyl)-2,5-dihydrofuran N, M, R, (O
DO2x) δppm: 1.60 (5HS, ), 1
70 (5HS,), 2.40-2.60 (4Hm,),
4.60 (IH8,), 4.64 (IH8,).

5.05 (IHt++ J=7Hz), 5.49 (I
H8,).

5.61 (IHbr, B,), 6.69 (5HS,) I
, R, (0HC4) cm-”: 2990.2
920, 2850, 1662, 1600°1570.1
285,1058,922,850° Reference Example 1 IL4 equipped with a stirrer, thermometer, dropping funnel, and cooler
Oily NaH7,2S' (11,115 mol) was placed in a Tulo flask, and washed with 30% of n-hexane under a nitrogen stream. After removing the hexane layer, the flask was dried with NaHf under reduced pressure. Then add dimethyl sulfoxide 150-
The mixture was heated and stirred at 5°C for 1.0 hour to prepare a dimesyl anion solution.

25℃ Chidoriethylenediamine 17? (115 moles)
490 g of tetrahydrofuran dissolved in tetrahydrofuran were added thereto, and the mixture was further cooled to -10°C. A solution of trimethylsulfonium iodide 3α6t (α15 mol) dissolved in dimethylsulfoxide 120- was added dropwise at -10°C, stirred for 2 minutes, and then 1-(2-hydroxyphenyl)-7-methyl-1,6 -Octarenin-5-one 11.5F (105 mol) Tetrahydrofuran 5
A solution dissolved in Ogo was added and stirred at -5°C for 1.0 hour.

Thereafter, the temperature was returned to room temperature for 1.0 hour, and 2N hydrochloric acid aqueous solution 8
The mixture was neutralized with 50% ethyl acetate and extracted twice with 500% ethyl acetate. The organic layers were combined and washed twice with 300 g of saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 10 f of a brown oil.

This was separated on a gold silica gel column as a pale yellow oil of 782F, 2-(2-hydroxy7enyl)-4-(<
-Methyl-3-pentenyl)-2,5-dihydrofuran was obtained (yield: 464%).

Reference Example 2 By the same operation as described in Reference Example 1, 1-(2-hydroxyphenyl)-1-butene-3-
The reaction was carried out using 2443 (115 mol) of 2
-(2-hydroxyphenyl)-4-methyl-2,5-
Dihydrofuran 11,7f was obtained as a white solid (yield 46%).

Melting point: 65-67° C. [Effects of the Invention] As explained above, according to the method of the present invention, unlike the conventional two-stage method, it is possible to oxidize the hydroquinone nucleus and the dihydrofuran nucleus all at once.

Moreover, it is advantageous in that the raw materials can be easily synthesized. Furthermore, among the target compounds obtained by the method of the present invention, there is a new compound that is the same type as a natural compound! Although rare, it is useful in that it has antibacterial activity, and the present invention is also useful in that it has become possible to synthesize and chemically supply it in large quantities.

Claims (1)

[Claims] A method for producing 2-quinoylfurans, which comprises oxidizing 1,2-(2-hydroxyphenyl)-2,5-dihydrofurans with potassium nitrosodisulfonate.