JPS61277674A - Phenolic derivative - Google Patents

Abstract

NEW MATERIAL:2-(2-Hydroxyphenyl)-4-(4-methyl-3-pentenyl)-2,5-dihydrofuran expressed by formula I. USE:A synthetic intermediate for compounds having drug effect, preservable stably at <=0 deg.C in N2 though decomposed by allowing to stand at room temperature, having antimicrobial activity and usable as a synthetic raw material for 2-quinoyl-4-(4-methyl-3-pentenyl)-furan expressed by formula III. PREPARATION:6-Methyl-5-hepten-2-ol and salicylaldehyde are subjected to aldol condensation in the presence of a basic catalyst to give 1-(2-hydroxyphenyl-7- methyl-1,6-cotadien-3-one expressed by formula III, which is then cyclized, preferably in the presence of a tertiary amine in a solvent to afford the aimed compound expressed by formula I which is a light yellow oily substance. The resultant compound expressed by formula I is oxidized with a compound expressed by formula V to afford the aimed compound expressed by formula II.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel compound useful as an intermediate for the synthesis of medicinally effective compounds.

[Conventional technology]

Conventionally, a substance called echinofuran, which is represented by the following formula (■), has been isolated as a pigment component from a chloroform extract of tissue cultured cells of a plant belonging to the family Murasaceae [Pharmaceutical Society of Japan 99th Annual Meeting Abstracts, page 206] (197
9)).

[Problem that the invention seeks to solve]

However, the above-mentioned echinofuran is only contained in trace amounts (approximately 3%) in natural purple violets and its tissue culture cells, and is an unstable substance, making it difficult to conduct research on its pharmacological effects. Inconvenient and dangerous.

The purpose of the present invention is to provide a novel compound that can be used as a synthetic intermediate, with the ultimate goal of synthetically obtaining a compound of the same type.

[Means for solving problems]

The present invention relates to a new compound, 2-(2-hydroxyphenyl)-4-(4
-Methyl-3-pentenyl)-2,5-dihydrofuran.

The compound of formula (1) of the present invention is, for example, 1-(2-hydroxyphenyl)-7-methyl-1,6 represented by the following formula I:
It can be synthesized by reacting -octarenin-3-one with dimethylsulfonium methylide 0H2=B(OHs)*i, preferably in the presence of a tertiary amine.

In the above cyclization reaction, addition of a tertiary amine improves yield and selectivity. Examples of suitable 6th amines include triethylenediamine (DAEOO) and N, N, N: y
''-tetramethylethylenediamine (TMKDA). For example, under the conditions that the molar ratio of the 5th amine to the compound of formula H is 50, and the molar ratio of dimethylsulfonium methylide to the compound of formula H is SO, tetrahydrofuran-dimethyl The reaction was carried out in sulfoxide at -5°C for 1.0 hour, and the results shown in Table 1 below were obtained.

Table 1 The compound of formula (■) of the present invention is obtained as a pale yellow oil,
It is useful as an intermediate in the synthesis of medicinal compounds. For example, a compound of formula ■? , potassium nitrosodisulfo/acid (
KOsS), N→0 (hereinafter referred to as Flemy salt), 2-quinoyl-4-(4-methyl-5-pentenyl)-furan represented by the following formula (2): υ is obtained. This compound of formula (1) has antibacterial activity and is useful as a medicine. The compound of formula (■) is a bright yellow solid, and like the compound of formula (■), it gradually decomposes and turns reddish-brown when left at room temperature, but it cannot be stored stably in nitrogen at temperatures below 0°C. I have discovered everything that can be done.

Furthermore, alternative compounds can be synthesized, for example, by aldol condensation of 6-methyl-5-hebuten-2-one and salicylaldehyde, each of which is a known compound, in the presence of a basic catalyst. .

In addition, dimethylsulfonium methylide, which is a reactant used in the synthesis of the compound of formula
It is obtained by reacting with aH1 and then reacting with trimethylsulfonium iodide gold.

〔Example〕

Hereinafter, the present invention will be explained in more detail with reference to Examples and Reference Examples, but the present invention is not limited thereto.

Example 1 1t4 equipped with stirrer, thermometer, dropping funnel, and cooler
Put 7,2t of oily NaH (α15 solu) into a tube flask, wash with 50ml of n-hexane under a nitrogen stream,
After removing the hexane layer, it was dried with NaHf under reduced pressure. Thereafter, 150 m@ of dimethyl sulfoxide was added, and the mixture was heated and stirred at 65°C for 1.0 hour to prepare a dimesyl anion solution.

Triethylenediamine (DABOO) 17f at 25℃
A solution of (α15 mol) dissolved in 490°C of tetrahydrofuran was added, and the mixture was further cooled to -10°C. A solution of trimethylsulfonium iodide 5Q, 6f (115 mol) dissolved in 120-dimethyl sulfoxide was added to
It was added dropwise at 0°C, stirred for 2 minutes, and then compound 11.5f (105 mol) of Reference Example 1 was added to 5 mols of tetrahydrofuran.
A solution dissolved in 0- was added and stirred at -5°C for 1.0 hour.

After that, the temperature was returned to room temperature for 1.0 hour, and the 2N hydrochloric acid water bath solution was
The mixture was neutralized with 50% ethyl acetate and extracted twice with 500% ethyl acetate. The organic NI was washed twice with 300% saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 102 as a brown oil.

This was separated using a silica gel column to give 2-(2-hydroxy7enyl)-4-(4
-Methyl-3-pentenyl)-2,5-dihydrofuran was obtained (yield 64%).

N0M, R, (CD01s) δppm: 1.5
8 (5H13,), 1.67 ('5HE1.), 2
．． 10-2.18 (4Hm, ), 4.60 (IHS,
), 4.64(1)! S.).

5.06 (IHta, r near Hz), 5.60
(IHS,).

7.01 (IHbr, 8.), 465-7.20 (4
Hm,).

7.91 (IHbr, 8.) Engineering, R, (0T104), n-s.

5350, 5010.2980.2910.2870°1662.1620,1585,14L6,1240°1060, 1040.985.920.878.830
゜Reference Example 1 (Synthesis of substitute compound) 50 equipped with a stirrer, thermometer, dropping funnel, and condenser
100fi of 30% NaOH aqueous solution in 0d4 Tulo flask
In addition, salicylaldehyde 20f ((L 164 mol)) was added dropwise at 20°C.

Change VC6-)f-5-heften-2-on10f(1
Dissolve 079 mol) in methanol 200- and make 9 liquid t-20
It was added dropwise at ℃ to make a homogeneous solution.

This reaction g'i was allowed to stand at 25°C for 144 hours to carry out complete aldol condensation, and then neutralized with concentrated hydrochloric acid at 80F.

Extract the neutralized solution three times with 200ml of chloroform, wash the combined chloroform layers with 100ml of water, and dry over anhydrous magnesium sulfate. After dispensing with magnesium sulfate, chloroform was distilled off under reduced pressure to obtain a brown oily substance.

This oily substance was dissolved in 100% of acetone and treated with activated carbon (white gimme powder) 51% at room temperature, and the acetone was distilled off under reduced pressure to obtain a pale yellow solid 'il&2F. This was crystallized from hexane mood to obtain 11.2F (α049 mol) of 1-(2-hydroxyphenyl)-7-methyl-1,6-octarenin-3-one. Melting point 124℃~1
26°C Reference Example 2 (Synthesis of Compound of Formula 1) Compound 1 of Formula 1 was placed in a 20-Eggplant flask. Of(4,
55 mmol) and tetrahydrofuran 5-, and 20
n-Butyllithium hexane solution (27% by weight) at °C
1.15? (4.79 mmol) was added and stirred for 5 minutes.

Thereafter, the solvent was distilled off to obtain the lithium salt (1). Furthermore,
Into a 200 sd4 flask equipped with a stirrer, a thermometer, and a condenser, a solution of the above-mentioned lithium salt dissolved in 10 (]- of water was added, and then 5.0 r (1a7 mmol) of Fremy salt was dissolved in a 1% NaHCO3 aqueous solution. 18% of the solution
The mixture was added at ℃ and further stirred at the same temperature for 50 hours.

After that, it was extracted twice with 100% of ether and 100% of it was extracted under reduced pressure.
The ether was distilled off at °C to obtain 1.02 f of a brown solid. Using a solvent of hexane/acetone = 5/1 (volume ratio) and a silica gel disk (5w) t', the product was completely collected under a nitrogen stream, and 2-quinoyl-4-(4- Methyl-3-pentenyl)furan is 10
9m? 2-quinoyl-4- as the obtained and unconverted intermediate
70 mf of (4-methyl-3-pentenyl)-2,5-dihydrofuran was obtained. As a precaution, 552 mf of the raw material ■ was recovered.

〔Effect of the invention〕

As explained above, the compounds of the present invention are useful as intermediates for the synthetic chemical production of medicinal compounds.

Claims (1)

[Claims] 1,2-(2-hydroxyphenyl)-4-(4-methyl-3-pentenyl)-2,5-dihydrofuran.