JPS5829947B2 - Method for producing 1-acyl-2-substituted-4-mercaptocyclopentane - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula (wherein R and R1 are alkyl or aryl groups, and is a group, X,
Y and Z cannot be hydrogen at the same time.

) The present invention relates to a method for producing 1-acyl-2-substituted-4-mercaptocyclopentane represented by:

More specifically, the present invention applies the general formula (wherein R and R1 are an alkyl group or an aryl group) under basic conditions.

1-acyl-4-mercaptocyclopentene represented by the general formula (wherein, X, Y and Z are hydrogen, an alkyl group, an aryl group, a carboxyl group, a carbonyl group, or a cyano group; cannot be hydrogen at the same time.

) The present invention relates to a method for producing I-acyl-2-substituted-4-mercaptocyclopentane represented by the general formula (I) by reacting it with an active methylene compound represented by the formula (I).

Many compounds with five-membered carbon rings exist in nature.

Examples include prostaglandin, jasmone, jasmonic acid, iridoids, which are generic names for cyclopentanopyrans, and hydroazulenes.

These compounds are known to be useful as physiologically active compounds or fragrances.

Products according to the invention are useful as intermediates for the synthesis of these compounds.

That is, the sulfur functional group can be substituted with another functional group, for example, the -SR group of the compound of general formula (I) can be replaced with -
By converting it into an OH group, it can become a precursor that can easily lead to the above five-membered carbon ring natural product.

The general formula (■
1-acyl-4-mercaptocyclopentene represented by ) can be easily formed by the method developed by the present inventors.

That is, the raw material (II ) can be formed [Fujisawa et al.
4th Annual Meeting of Chemicals, Lecture Proceedings 3FO3 (1976)].

Further, the active methylene compound represented by the general formula (III), which is one of the raw material compounds, is a compound that can be easily obtained industrially.

The method of the present invention requires that the compound of the general formula (II) and the compound of the general formula (III) be reacted in the presence of a base.

As the base, alkali metal hydroxides and alkoxides such as sodium hydroxide, potassium hydroxide, sodium alkoxide, and potassium alkoxide can be suitably used.

The amount of these bases to be used is 10% by weight based on the base H(III).

Further, in carrying out the reaction, it is preferable to use a solvent, and for example, water, ether, tetrahydrofuran, dimethoxyethane, benzene, toluene, alcohol, etc. can be suitably used.

The reaction proceeds smoothly at room temperature without using any special heating or cooling means.

In the present invention, especially in the case of ethyl acetoacetate and acetylacetone, which are easily enolized as active methylene compounds, the target compounds tend to form stable bicyclic compounds with further reaction, but these reactions are also applicable to the present invention. This is one aspect.

For example, when ace-1-ethyl acetate is reacted with 1-acetyl-4-phenylthi-1-cyclopentene in ethanol, 2-ethoxycarbonyl-5-hydroxy-5-methyl-8-phenylthio expressed by the following formula is produced. Bicyclo [4.3.0
1°6] Nonan-3-one was obtained, and this structure was confirmed by leading to an aromatic cyclized indane derivative through a dehydration reaction.

The present invention will be explained in more detail with reference to Examples below.

Example 1 55% oily sodium hydride 0.0181 (0.41 m
mole) and absolute ethanol2. Diethyl malonate 0.650'? C4, 1 mmole) in absolute ethanol (4, □m ~ solution, then 1-acetyl 4
-phenylthio-l-cyclopentene 0.4371 (
A solution of 2.0 mmole) of ethanol (2.0 mA) was added, and the mixture was stirred at room temperature for 25 hours.

Thereafter, the reaction solution was neutralized by adding IN hydrochloric acid, and then extracted with ether.

The ether layer was washed with saturated brine, dried over MgSO4, the ether was distilled off, and the residue was purified by column chromatography to obtain 1-acetyl-2-jethoxycarbonylmethyl-4-phenylthiocyclopentane as an oily substance. .534
I got f.

Yield 70%.

NMR (CCI4): δ1.23 (6H, t, J=
8.0Hz), 2.08 (3H,s), 4.09
(4H1dd, J=7.3Hz), 7.23 (5H
, bs).

MS (70eV): m/e 378 (M+, 4
8%).

Example 2 55% oily sodium hydride 0.018P (0.4mm
ole, l in anhydrous THF (20 m
0.0, then malononitrile 0.265 f.
t (4,0 mmole, l THF (5,0 m
0 solution was added.

In this, 1-acetyl-4-phenylthio-1-cyclopentene 0.4341 [2.0 mmole, 1 of TH
F solution was added and stirred at room temperature for 2 hours.

The reaction solution was neutralized by adding IN hydrochloric acid and then extracted with ether.

The ether layer was washed with saturated brine, dried over MgSO4,
Ether was distilled off, and excess malononitrile was further distilled off from the residue under vacuum to obtain 0.53 g of 1-acetyl-2-dicyanomethyl 4-phenylthiocyclopentane as an oil.
9? I got it.

Yield 95%. NMR (CDCI 3): δ1.98 (
3H, bs ), 7.27 (5H, bs ).

MS (70eV): m/e284 (M+ 18%).

Example 3 Similarly to Example 1, ethoxide (0,41amole
ethyl cyanoacetate/110.4 in 1 ethanol solution
An ethanol solution of 461 [4.1 mmole] and an ethanol solution of 0.435 ft (2.0 mmole) of 1-acetyl-4-phenylthio-1-cyclocyclopentene were added, and the mixture was stirred at room temperature for 41 hours.

Here, sodium hydride 0.017 f (0.40 mm
ole) was added and stirring was continued for an additional 53 hours.

Thereafter, the reaction solution was neutralized with IN hydrochloric acid and extracted with ether.

The ether layer was washed with saturated brine, dried over MgSO4, the ether was distilled off, and excess cyanoacetic acid was distilled off under vacuum to form a viscous oil, 1-acetyl-2-cyanoethoxycarbonylmethyl-4. -Phenylthiocyclopentane 0.573L? I got it.

Yield 87%. NMR (CC14): δ1.27 (3
H,t, , J=7.5Hz), 2.08(3H,s)
, 4.18 (2H, m), 7.18 (5H,, bs
).

MS (70eV) 2m/e 331 (M
+18%).

Example 4 Same as Example 1 55% oily sodium hydride 0.04
4 ft (1, OyrLmole), ethyl acetoacetate 1.30PC10mmole] and] 1-acetyl-4-phenylthio 1-cyclopentene 1.09f
(Reacted in ethanol using 5.0 mmole, l).

After 27 hours, white crystals precipitated were separated by filtration, and the filtrate was heated under reflux for 4 hours, then diluted with methylene chloride, washed with saturated brine, and dried over MgSO4.

After methylene chloride was distilled off and excess ethyl acetoacetate was distilled off under vacuum, it was isolated and purified using column chromatography (Sin2) to obtain 2-ethoxycarbonyl-5- as white crystals.
Hydroxy-5-methyl 8-phenylthiobicyclo[4
・3・01°6] Nonane-3-one total 0.781P
I got it.

Yield 45%.

Melting point: 158-161°C NMR (δ6-acetone): δ1.18 (3H1t),
1.30 (3H1S), 1.65 (IH, m),
1.92 (3H, m), 2.37 (IH, dlJ-1
4,5Hz), 2.64 (tH,d, J=14
．． 5Hz), 2.80 (IH, m), 3.32 (I
H.

d, J=12.3Hz), 3.92 (LH, m),
4.12 (2H, m), 7.33 (5H1m).

MS (70eV): m/e 348 (M+ 30%
).

Example 5 Same as Example 2 55% oily sodium hydride 0.01
8? (0.41 mmole), ethyl acetoacetate 0.521? (4,0 mmole) and 1-acetyl-4-phenylthio-1-cyclopentene 0.4
37? (2.0 mmole) was used to react in THF.

The crude product was isolated and purified by column chroma) (SiO□) to give 2-ethoxycarbonyl-5-hydroxy-5-methyl-8-phenylthiobicyclo[4.3] as white crystals.
・01°6] Nonane-3one 0.171 was obtained.

Yield 24%. Example 6 Same as Example 2 55% oily sodium hydride 0.06
21 (1.4 mmole), acetylacetone 1.
401f (14rrLmole) and 1-acetyl-4-phenylthio-1-cyclopentene 1.522f
! (7,0 mmole, :l) was reacted in TI(F).

The reaction solution was heated under reflux for 28 hours. The crude product was isolated and purified by column chromatography (SiO2) to give 2-acetyl-5-hydroxy-5-methyl-8-phenylthiobicyclo[4.3.01°6]nonan-3-one 0.3 as crystals.
26'i? I got it.

Yield 15%. NMR (δ6-acetone): δ1.30
(3H,s), 2.07 (3H,s), 3.51
(IH, d), 3.93 (IH, m), 7.27 (
5H, bs).

MS (70eV): m/e 318 (M+ 16%)
.

Claims (1)

[Scope of Claims] 1. A 1-acyl-4 pentene represented by the general formula % is reacted with an active methylene compound represented by the general formula % in the presence of a base. Method for producing 2-substituted-4-mercaptocyclopentane [wherein R and R1 are an alkyl group or an aryl group, and X, Y and Z are hydrogen, an alkyl group, an aryl group, a carboxyl group, a carbonyl group, or a cyano group, and X, Y and Z cannot be hydrogen at the same time. ].