JPS61277646A - Phenol derivative - Google Patents

Abstract

NEW MATERIAL:1-(2-Hydroxyphenyl)-7-methyl-1,6-octadien-3-one of formula I. USE:A synthetic intermediate for a compound having pharmaceutical action. Although the decomposition of the compound takes place by leaving at room temperature, the compound can be stored stably at <=0 deg.C. It can be used as a synthetic raw material of 2-quinonyl-4-(4-methyl-3-pentenyl) furan of formula II having antibacterial activity and useful as a medicinal drug. PREPARATION:The objective compound of formula I can be produced in the form of yellow crystal, by reacting diketene with 2-methyl-3-buten-2-ol in the presence of a catalyst such as triethylamine, heating the product in N2 stream to effect the decarbonation and rearrangement reaction, and carrying out the aldol condensation reaction of the resultant 6-methyl-5-hepten-2-one with salicyl- aldehyde in a solvent in the presence of a basic catalyst such as NaOH. The obtained compound of formula I can be converted to the compound of formula II by reacting with the compound of formula III in the presence of a tertiary amine, etc., and oxidizing with the compound of formula IV.

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 echinoalan, which has 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 [Pharmaceutical Society of Japan 99th Annual Abstracts Collection No. Page (197
9)).

[Problem that the invention seeks to solve]

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

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 novel compound, 1-(2-hydroxyphenyl)-7-methyl-1,6-octalenin-3-one, which is represented by the following formula (1).

The compound of formula (1) of the present invention can be synthesized, for example, by aldol condensation of 6-methyl-5-hebuten-2-one and salicylaldehyde, each of which is a known metal compound, in the presence of a basic catalyst. I can do it.

The basic catalyst used may be one commonly used for aldol condensation, such as an aqueous sodium hydroxide solution. In this reaction, the higher the alkali concentration, the higher the yield of the target compound of formula H. For example, the molar specific power of salicylaldehyde to 6-methyl-5-hebuten-2-one is 2.
0. When the reaction is carried out at 15°C in a water-ethanol (1:1) solvent under conditions where the molar ratio of NaOH to salicylaldehyde is 5.0, the reaction time is Although the yield of compound 2 was only 41% in 10 days, the yield at a concentration of 30% by weight improved to 61% even after a reaction time of 6 days.

The compound of formula (1) was obtained as yellow crystals, and analysis of its nuclear magnetic resonance spectrum revealed that the double bond at position 1 was only in the E configuration.

Therefore, the compound of formula (1) is useful as an intermediate for the synthesis of medicinally effective compounds. For example, in the compound 2), dimethylsulfonium methylide 0Hs=S (OEsh 'c,
Preferably, when the reaction is carried out in the presence of a tertiary amine, 2-(2-hydroxyphenyl)-4-(4
-methyl-3-pentenyl) -2,5-dihydro7rane is obtained in a yield of around 60%.

Next, the compound of formula I is oxidized with potassium nitrosodisulfone (KOsS)*N-+O (hereinafter referred to as Flemy's salt) to form 2-quinoyl-4-(4-)5- represented by the following formula (■): -3-pentenyl)-furan is obtained. This compound of formula ■ is
It has antibacterial activity and is useful as a medicine. In addition,
Compound 2 is a bright yellow solid; like the compound of formula I, it gradually decomposes and turns reddish-brown when left at room temperature; however, it can be stored stably in nitrogen at temperatures below 0°C. I found out.

Furthermore, 6- which is a raw material for the synthesis of the compound of formula (1) of the present invention
Methyl-5-hebuten-2-one is produced by reacting diketene and 2-methyl-3-buten-2-ol, preferably in the presence of a catalyst with low nucleophilic force such as triethylamine. , 1-dimethyl-2-propenyl) acetoacetyla, followed by heating under a nitrogen stream,
It can be obtained by allowing decarboxylation and rearrangement reactions to proceed and purifying the product by distillation.

In addition, dimethylsulfonium methylide, which is a reactant used in the synthesis of compound 2H, is added to dimethylsulfoxide with N
It is obtained by reacting with aHf and then reacting with trimethylsulfonium iodide.

〔Example〕

Hereinafter, more specific Ka
BA, but the present invention is not limited thereto.

Example 1 500 equipped with stirrer, thermometer, dropping funnel, and cooler
Wt4 turophras = + 30% NaOH aqueous solution 100f
In addition, salicylaldehyde 20f (α164 mol) was added dropwise at 20°C.

Furthermore, 6-) If 5-hebuten-2-one 10t (α
079 mol) A solution dissolved in 200 parts of total methanol at 20°C.
Add dropwise to make a homogeneous solution. This reaction solution was heated to 25℃ for 14 hours.
Leave to stand for 4 hours to complete aldol condensation and concentrate hydrochloric acid 80? It was neutralized. The neutralized solution was extracted three times with 200% chloroform, washed with 100% water together with the chloroform NI gold, and dried over anhydrous magnesium sulfate. magnesium sulfate
After separation, chloroform was distilled off under reduced pressure to obtain a brown oily substance.

This oily substance was dissolved in 100% acetone and treated with activated carbon (white cedar A powder) at room temperature, and the acetone gold was distilled off under reduced pressure to obtain 152f pale yellow solid. This was crystallized from 500% hexane to obtain 11.2 F (49 moles of LO) of 1-(2-hydroxyphenyl)-7-methyl-1,6-octadien-3-one. Melting point 124℃~1
26°C N, M, R, (CD0L,) δppm: 1.65
(5HS,), 1.69 (5H8,), 2.40 (
2Hd, t, J=2.7Hz), 2.74(5Hd,
t, J==2°7Hz), 5.17(IHt,, T==
7Hz), &74~7.48(4E a,
&97(IH(1,,T==16H2).

7.94 (IHd, y=16az) Engineering, R, (011104) ff1-X:5560.
5000.2970.2910.1705°1670,
1650.1595.1450.1252°1152,
10B0.978.752 Reference Example 1 (Synthesis of compound of formula 1) 1t4 equipped with a stirrer, thermometer, dropping funnel, and condenser
Oily Nag 7.2 f (α15 mol) was placed in a Tulo flask, washed with 50 d' of n-hexane under a nitrogen stream, and after removing the xane layer, NaH'i was added under reduced pressure.
The shoes were dry. Then 150 d'i of dimethyl sulfoxide
In addition, the mixture was heated and stirred at 65°C for 1.0 hour, and the dimesyl anion solution was added thereto.

Triethylenediamine 179 ((L15 mol) at 25°C
A solution of 490° C. in tetrahydrofuran was added thereto, and the mixture was further cooled to -10°C. A solution of trimethylsulfonium iodide 50.6f (115 mol) dissolved in t-dimethylsulfoxide 120- was added dropwise at -10°C, stirred for 2 minutes, and then the compound of Example 1 ω) 11.
A solution of 51 (105 mol) dissolved in 50% of tetrahydrofuran was added, and the mixture was 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
Neutralize with 0- and extract twice with vinegar and ethyl 500-. The organic layers were combined and washed twice with 300ml 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 to give 2-(2-hydroxyphenyl)-4- as a pale yellow oil of 7.82 F.
(4-Methyl-5-pentenyl)-2,5-dihydrofuran was obtained (yield 64%).

Reference Example 2 (Synthesis of Compound 2) In a 20-Eggplant flask, compound 1. Of(4,5
5 mmol) and tetrahydrofuran 5-, and heated to 20°C.
n-butyllithium hexane solution (27% by weight) 1
．． 15 F (4.79 mmol) was added and stirred for 5 minutes.

Thereafter, the solvent was distilled off to obtain the lithium salt (1). Furthermore,
In a 9200 d4 flask equipped with a stirrer, thermometer, and condenser, add a solution of the above lithium salt dissolved in 100% water, and add Flemy salt5. Of (1a 7 mmol) f 14 A solution dissolved in NaHOO1 aqueous solution was added at 18°C, and then at the same temperature! I stirred for LO time.

After that, it was extracted twice with 100% of ether and 100% of it was extracted under reduced pressure.
Ether was distilled off at °C to obtain 1.02f of brown solid.

This brown solid was mixed with a solvent of hexane/acetone ==5/1 (volume ratio) and a silica gel disc (5 m).
When the product was separated under a nitrogen stream, it was found that 2-quinoyl-
4-(4-methyl-5-pentenyl)furan force 109m
f and 2-quinoyl-4-(4
-Methyl-3-pentenyl)-2,5-dihydrofuran at 70 mf. In addition, 552 mF of the raw material (■) was recovered.

〔Effect of the invention〕

As explained above, the compound of the present invention is useful as a ninth intermediate in the synthetic chemical development of medicinal compounds.

Claims (1)

[Claims] 1,1-(2-hydroxyphenyl)-7-methyl-1
,6-octagen-3-one.