JPH02311471A - Gamma-alkyl-gamma-phenylsulfonyl-alpha,beta-unsaturated butyrolactone - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [R1 and R2 are H, alkyl or aryl; R3 is alkyl (including allyl)]. EXAMPLE:3,4-Dimethyl-4-phenylsulfonyl-2-buten-4-olide. USE:A synthetic intermediate for natural flavors, insect pheromones and antitumor substances. PREPARATION:A compound expressed by formula II is reacted with a compound expressed by formula III (X is halogen) in the presence of a base, such as an alkali metal salt of a secondary amine, such as lithium diisopropylamide, or an alkyl-alkali metal, in a solvent, such as tetrahydrofuran, to selectively and economically afford the compound expressed by formula I in high yield.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a novel γ-alkyl-γ-phenylsulfonyl-α,β-unsaturated cutyrolactone. More specifically, the present invention relates to γ-alkyl-γ-phenyl represented by the general formula [1] where R1 and R2 are a hydrogen atom, an alkyl group, or an aryl group, and R1 is an alkyl group (including an allyl group). It is related to sulfonyl-α,β-unsaturated petyrolactone, and this compound is important as an intermediate in the synthesis of natural flavors, insect pheromones, and antitumor substances.

[Prior Art] One of the fields of application of the present invention is the use as a raw material for the synthesis of γ-alkyl-a, β-unsaturated butyrolactone.
Previously, the method for producing this type of compound was described in German patent 1.
072.629 is known, in which γ-alkyl-α,β-unsaturated butyrolactone is produced by reacting an alkyl-substituted maleic anhydride with a Grignard reagent and then hydrolyzing the product. It has been pointed out that the drawback is that a large amount of by-products are produced. [G.

PATTENDEN: Fortsch, chew
, Org, Naturstoffe Volume 35, 16
Pages 6 to 167, published in J, 1976. In addition to the above, 1-yn-3-ol is synthesized by reacting a carbonyl compound with an alkyl group to be introduced into the γ-position of butyrolactone with sodium acetylide in a solution. A departing
, Nobuhara et al.'s method [Agr, Biol,
chem, 34.1745 (197ON, Method starting from phenylthioacetic acid [K, Iwai et al chem
istry Letters, P, 385 (19
74 N, P, 1237 (1974), Method using α-phenylthioketone [P, Brownbri
dge et al., J.C.S.Chem.Comm.
P, 465 (1977), Perkin, J.C.S.
P, 2751 (1981) l, etc. are known, but
Each method has problems such as expensive raw materials, complicated processes, large amounts of by-products, and low yields.

[Problems to be Solved by the Invention] An object of the present invention is to produce γ-alkyl-α, β-unsaturated butyrolactone, which is a synthetic intermediate of the compound, in a selective reaction and in a high yield. -Phenylsulfonyl-α,β-unsaturated unsaturated cutyrolactone The object of the present invention is to provide an industrially advantageous production method.

[Means and effects for solving the problem] The present inventors
As a result of extensive research into an economically superior method that is selective in the reaction and capable of producing γ-alkyl-α,β-unsaturated butyrolactone in high yield, we found that γ-alkyl-γ-phenylsulfonyl-α,β-unsaturated They succeeded in synthesizing saturated unsaturated cutyrolactone and found that the desired effect can be obtained when this compound is used as a raw material, leading to the completion of the present invention.

The present invention also relates to general formula E, where R, R, is a hydrogen atom, an alkyl group, or an aryl group, and R3 is an alkyl group (including an allyl group)]
γ-alkyl-γ-phenylsulfonyl-
The present invention relates to a method for producing α,β-unsaturated cutyrolactone.

In the definition of the above general formula, the alkyl groups for R and R2 include methyl group, ethyl group, n-propyl group, isopropyl group, lobutyl group, 5ec-butyl group, tert
-Lower alkyl groups such as butyl, aryl groups include phenyl, tolyl, etc., and R1 alkyl groups include methyl, butyl, octyl, allyl,
Examples include methallyl group, prenyl group, and geranyl group.

The present invention will be explained in detail below.

γ-alkyl-γ-phenylsulfonyl-〇 of the present invention,
β-Unsaturated cutyrolactone 1 is produced, for example, by the following method.

Bases such as diisopropylamine, hexamethyl [In the above reaction formula, R8 is an alkyl group (including allyl group)]
where X is a halogen atom, R3 and R2 are a hydrogen atom, an alkyl group or an aryl group. ] Further, examples of the solvent to be used include ether solvents such as tetrahydrofuran and diethyl ether.

Note that α-phenylsulfonyl-α,β-unsaturated butyrolactone of the general formula is preferably produced by the method described in Japanese Patent Application No. 1-39465 [Title of the invention: Process for producing functionalized butenolide 1] by the present inventors. .

That is, it can be obtained by reacting 4-halogeno-2-butene-4- of the following general formula with sodium phenylsulfinate or the like.

[Example j] Examples of the present invention will be shown below to specifically explain the present invention.

Last JL example.”

Dry tetrahydrofuran 5raR was placed in a 50 ml eggplant-shaped flask, and after the flask was purged with nitrogen, 0.163 g (1,61 mmof') of diisopropylamine was added dropwise. After that, the liquid temperature was cooled to 0°C, and 0.9 mR (1,39 mmoi') of n-hexane solution of n-butyllithium was prepared.
was added dropwise and stirred for 1 hour to prepare lithium diisopropylamide.

Subsequently, it was cooled to -78°C, and dried tetrahydrofuran 3
3-methyl-4-phenylsulfonyl 2 dissolved in ml
-butene-4-olide 0.232 g (0.96 mm
0.4 of methyl iodide dissolved in 3 tal of dry tetrahydrofuran was added dropwise to the reaction solution and stirred for 30 minutes.
81 g (3.39 mmoi') was added dropwise, and the reaction was continued for 2 hours with stirring. Thereafter, the temperature was raised to room temperature, and after stirring for 24 hours, a saturated aqueous solution of ammonium chloride was added to stop the reaction. Subsequently, water was added to dissolve the salt, and extraction was performed with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate.

After concentrating the dried organic layer, it was subjected to flash column chromatography packed with silica gel (developing agent: n-hexane ethyl diacetate = 4:1) to separate the components in the reaction solution, and 3,4-dimethyl-4 0.269 g of -phenylsulfonyl-2-butene-4-olide was obtained. Yield is 76%. The physical properties of the substance are as follows (
It is.

'H-NMR (d CDCj) 3) 1.85 (s, 3H), 2.35 (s, 3) 1),
5.84 (BS, IH).

7.30-8.10 (m, 5H) IR (cm-') 2900, 1780.1320 Nobu Udo Put dry tetrahydrofuran 3- into a 50 mB eggplant-shaped flask, and after purging with nitrogen, diisopropylamine 0.1
72 g (1,72 ma+oi') was added dropwise and dissolved in tetrahydrofuran. After cooling the concentrated liquid to 0°C, 0.9 ml of n-hexane solution of n-butyllithium (139 m
3-methyl-4-phenylsulfonyl-2-butene dissolved in dry tetrahydrofuran was added dropwise and stirred for 30 minutes to prepare lithium diisopropylamide. After cooling the liquid to -78°C, 3-methyl-4-phenylsulfonyl-2-butene- 0.300 g (1,27 am+oi') of 4-olide was added dropwise, and then 2 equivalents of hexamethylphosphoric acid triamide was added, and after stirring for 1 hour, 3 fl11 of dry tetrahydrofuran was added!
0.819 g of methallyl bromide (1,40
mmoi') was added dropwise, and the mixture was further stirred for 1 hour. The reaction solution was then heated to 0°C, a saturated aqueous solution of ammonium chloride was added to stop the reaction, water was added to dissolve the salt, extraction was performed with ethyl acetate, and the organic layer was washed with saturated brine. , dried over sodium sulfate, and then concentrated and subjected to flash column chromatography packed with silica gel (developing agent: n-hexane: ethyl acetate = 5:1) to separate the components in the reaction mixture.
0.260 g of 4-(2-methyl-2-propene)-4-7enylsulfonyl-2-butene-4-olide was obtained. Yield is 70%. The physical properties of the substance are as follows.

'H-NMR (dCDC) 1.65 (s, 3N), 2.35 (s, 3) 1),
2.90-3.20 (+n, 2H) 4, 6 (1-5.0
0 (m, 2 old, 5.85 (bs, IH).

7.30-8.00 (m, 5H) IR (cab-') 2900, 1780.1620.1450111 The same procedure as in Examples 1 and 2 was carried out. The contents are shown in the table below.

Fruit 11-eup 3-methyl-4-phenylsulfonyl-2-butene-4
-Production of 3-methyl-4-(3-methyl-2-butenyl)-4-phenylsulfonyl-2-butene-4-olide from olide Dry tetrahydrofuran 5a+1' was placed in a 50IIIP eggplant-shaped flask, and the atmosphere was replaced with nitrogen. , 0.107 g (1,06 mmol) of diisopropylamine was added dropwise and dissolved in tetrahydrofuran. After cooling the liquid temperature to 0°C, n-
Butyllithium n-hexane solution 0.6ml) (0,
91a+moi') was added dropwise and stirred for 30 minutes to prepare lithium diisopropylamide. Subsequently, after cooling the liquid to -78°C, 0.202 g of 3-methyl-4-phenylsulfonyl-2-butene-4-olide (0.84 mInof
') was added dropwise, and then hexamethyl phosphoric acid triamide 0
,2ffi! (1,00 mmoN) was added and stirred for 1 hour. Next, 0.170 g of prenylbromide (1,14 mo+o
After adding f) dropwise and stirring, the temperature was raised and when the temperature reached the liquid temperature and room temperature, a saturated aqueous solution of ammonium chloride was added to stop the reaction. Subsequently, water was added to dissolve the salt, extraction was performed with ethyl acetate, and the organic layer was washed with saturated brine, dried over dry sodium sulfate, concentrated, and subjected to flash column chromatography packed with silica gel (developing agent 20- 3-methyl-4-(3-methyl-2
-butenyl)74-phenylsulfonyl-2-butene-
0.215 g of 4-olide was obtained. Yield is 84%.

[Effect of the invention] γ-alkyl-γ-phenylsulfonyl-a of the present invention,
If β-unsaturated prorolactone is used, γ-alkyl-α
, β-unsaturated butyrolactone can be selectively obtained in high yield, and therefore the industrial significance of the present invention is extremely large.

Claims (2)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R_1 and R_2 are hydrogen atoms, alkyl groups or aryl groups, and R_3 is an alkyl group (including allyl group)] γ- Alkyl-γ-phenylsulfonyl-α,β-unsaturated butyrolactone. (2) Compounds represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R_1 and R_2 are hydrogen atoms, alkyl groups, or aryl groups] and the general formula R_3
-X[R_3 is an alkyl group (including allyl group),
X is a halogen atom. ],
A general formula consisting of a reaction in the presence of an alkali metal salt of a secondary amine such as lithium diisopropylamide or a base such as an alkyl alkali metal ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R_1, R_2, R_3 are γ-alkyl-γ-phenylsulfonyl-α,β represented by [same as above]
- A method for producing unsaturated butyrolactone.