JPS6042788B2 - Novel substituted cyclohexene derivatives and their production method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel substituted cyclohexene derivatives and processes for their production.

The following formula S(O)R^ [wherein R^ represents a substituted or unsubstituted alkyl, aryl, alkylaryl or aralkyl group, n represents a number of 0, 1 or 2, and the dotted line is indicated by this Indicates the presence of a double bond at one of the positions]
The compound represented by is known and is useful, for example, as a synthetic intermediate for deoxytrisboron, which has the effect of promoting the production of carotenes in microbiological or lotine production methods (Japanese Patent Application Laid-open No. 133252/1983). , same 5
2-937, etc.).

The present invention provides a novel substituted cyclohexene derivative in which one mel group at the 6-position of the cyclohexene ring is modified with a functional group in the compound represented by the above formula, thereby imparting value as an intermediate for the synthesis of trisborone and trisboronic acids. The compound according to the present invention is represented by the following formula (1).

In formula (1), R1 and R2 may be the same or different and each represents a phenyl group which may be substituted with a methyl group, etc., n represents O or the number of 1,
A dotted line represents the presence of a double bond at one of the indicated positions. The compounds of the present invention represented by formula (1) include sulfide (n=0) and sulfoxide (n=1) depending on n of the S(0)NR2 group modifying the methyl group.

The methyl group modified with this S(0)NR2 group can be converted into a formyl group, which is important for deriving the compound into the final substance. For example, 2●6-dimethyl-6-phenylthiomethyl-1-phenylsulfonylmethylcyclohexene-1 [in the formula, Ph means a phenyl group] is,
After reacting with sulfuryl chloride in refluxing carbon tetrachloride,
When refluxed in a 98% acetone aqueous solution in the presence of cupric chloride and cupric oxide, 2,6-dimethyl-6-formyl-1
-Phenylsulfonylmethylcyclohexene-1.

This formyl compound can be led to trisboronic acids through the following synthetic route. [R1 and R2 in formula (■)
has the same meaning as in formula (1)] in the presence of an acidic catalyst, and if desired, the thio group (-S-) in the product is oxidized to a sulfinyl group (↑).
-q- Manufactured by.

The compound of formula (■) is obtained by halogenating the hydroxygeranyl compound represented by the following formula (■) with the action of a halogenating agent such as phosphorus tribromide or hydrogen chloride, and then subjecting the resulting halide to alkali metal hydroxide. In the presence of the formula R2
SH [in the formula, R2 has the same meaning as in formula (1)]
It can be prepared by reacting with the thiophenols shown below.

The ring-closing reaction of the compound of formula (■) can be carried out using acidic catalysts such as protonic acids such as formic acid, sulfuric acid, trichloroacetic acid, hydrochloric acid, p-toluenesulfonic acid, and phosphoric acid, boron trifluoride, boron trifluoride etherate, and iron chloride. This can be carried out by a method known per se using a Lewis acid such as zinc chloride or zinc bromide. Two or more types of acidic catalysts may be used in combination; for example, when sulfuric acid is used in combination with acetic acid, better reaction results can be obtained than when sulfuric acid is used alone. The amount of acidic catalyst used is approximately 0.01 per mole of the compound of formula (■)
It is preferred to have a mole or more, especially about 0.05 mole or more. The acidic catalyst may be used in a large amount, but from the viewpoint of reaction operation and waste liquid treatment, it is preferably about 120 mol or less, especially about 10 mol or less, per 1 mol of the compound of formula (■). The ring-closing reaction is preferably carried out in the presence of a solvent, and suitable solvents include benzene, toluene, xylene, pentane, hexane, heptane, chloroform, carbon tetrachloride, methylene chloride, dioxane, tetrahydrofuran, diethyl ether, diethylene glycol, dimethyl ether, Mention may be made of aromatic hydrocarbons such as nitromethane, aliphatic hydrocarbons, halogenated hydrocarbons, nitrated hydrocarbons, ethers. Usable reaction temperatures range from as low as -70°C to as high as 150°C. The ring-closing reaction product has the following formula [wherein R1
. can be oxidized to a sulfinyl group. The ring-closing reaction product of the compound of formula (■) and its oxide often contain both of the following isomers (α-integral and β-integral) regarding the double bond at the position indicated by the dotted line in formula (1).

The production ratio of α-unit and β-unit changes depending on the temperature, type of acidic catalyst, and type of solvent in the ring-closing reaction of the compound of formula (■), and by appropriately selecting these conditions, one isomer can be It is also possible to selectively generate only the body.

The isomer mixture can be easily separated into each component (a) by crystallizing α, and the isomer mixture thus separated or the isomer mixture can be subjected to an isomerization reaction. It is also possible to achieve an increased yield of the desired isomer by applying For example, by heating an α-unit in the presence of p-toluenesulfonic acid, it is possible to isomerize it into a β-unit. Note that the present invention does not specify any stereoisomers based on the conformation of the compound of formula (1). Next, the present invention will be specifically explained with reference to Examples.

Example 1 (1) 20 mg (
stomach). 50 mol) of sodium hydroxide was weighed out, and after purging with nitrogen, 2 mL of ethanol was added, and 0.05 mt (0.49 mmol) of thiophenol was slowly added dropwise to this while stirring in an ice bath.

Immediately after the addition, the contents were returned to room temperature and stirred to dissolve approximately 1 ml of ethanol.
45.1 mg (0.41 mol) of 8-promugelanyl phenyl sulfone was slowly added dropwise. Approximately 1 at room temperature after dropping
5! Stirred for f minutes. After the reaction, the reaction mixture was poured onto about 5 ml of ice water and about 5 ml of saturated sodium bicarbonate solution, and about 3 ml
The mixture was extracted with ether three times. The ether layer was washed twice with saturated brine, dried over anhydrous sodium sulfate, and then the solvent was distilled off using a rotary evaporator. By-product diphenyl disulfide was separated from the obtained crude product by silica gel column chromatography (developing solvent benzene) to obtain 156.2 m9 of 8-phenylthiogeranylphenyl sulfone as a yellowish brown oil (yield 99%). .

40 mg of 8-phenylthiogeranyl phenyl sulfone (4) in a 30 ml eggplant flask. 1 mmol) was weighed out, and 5 ml of acetic acid was added to dissolve it.

To this, 0.5 ml of sulfuric acid was slowly added drop by drop at room temperature and stirred vigorously. After about 2 hours, about 15 m
The reaction was stopped by adding t of ice water, and extracted three times with about 3n1 of benzene. The benzene layer was washed three times with saturated aqueous sodium bicarbonate and then twice with saturated brine, and then dried over anhydrous sodium sulfate. The crude product obtained by distilling off the solvent from the benzene layer using a rotary evaporator was purified by passing it through a short silica gel column (developing solvent: benzene ethyl diacetate 10:1). 32 m9 of -phenylsulfonylmethyl-3-phenylthiomethylcyclohexene was obtained (yield: 80%).
-This cyclohexene derivative is 9/1 of α-unit and β-unit.
They were mixtures, and could be separated by crystallizing the α-unit from n-hexane. M. p. l
Ol~107C ■R (NujOl) 3063, 1676, 1650,
1582, 1302 (SO2), 1081, 1021,
74巳684c7n-1NMR(δ,CDCl,)1.
03 (S,.3H..CH3) 1.12-1.36 (m1?, CH2) 1.49 (D..J=2Hz,.3H..CH3) 19
0-2.08 (M., 2H..qdan2-C=C) 2.4
2-2.62 (MllH,.CH) 2.80-3.40
(Dd..J=5Hz1J=15Hz..sha LCU2-
SO2-) 42.98(
S. , 2H. ．． C. JJ2-S-) 5.32 (ratio, 1H
、． CH=C) 7.12-8.02 (MllOH..shah) NMR (δ, CDCl3) 1.09 (S,.3H.
．． CH3) 1.17-1.48 (M..2H..CH2) 1.68
(D., J=1.5Hz., 3H..CH3) 1.84
-2.12 (M..2l(,C...2-C=C)2.16
-2.53(MllH..CH)2.88-3.50(
Dd,. J=5Hz,. J=15Hz12H1CU2-
SO2-)3.06 (S..2H,.CM2-S-)5
．． 36 (ratio, 1H,.C = C) 7.08-8.01 (MllOH..2Ph) NMR (
δ, CDCI3) 1.28 (S, .3F[, CH3) 1.36-1.63 (M, .4H..2CH2) 1.7
3 (S.3H..CH3) 1.95-2.22 (M..
2H,. CU2-C=C)3.15(S.s2ll,.
C...2-S-)3.93(Dd..J=14Hz..J
=19Hz. ．． 2H. ．． Cdan21SO2-)7.09-
8.01 (MllOH, .2Ph) IR of α-, α″- and β integral mixture (Neat) 3062, 2972,
2939s167011645, 1585, 1480,
1444, 1305 (SO2), 1146 (SO2),
1085, 102λ742, 688cT1-1 Example 2 1,3-dimethyl-2- prepared in the same manner as Example 1
Dissolve 0.1 mole of phenylsulfonylmethyl-3-phenylthiomethyl-1-cyclohexene in 10 times the mole of acetic acid, and dropwise add 0.1 mole of peracetic acid while maintaining the temperature at 0°C.
A time reaction was performed.

The reaction mixture was poured into water, extracted with ether, and the ether layer was washed and dried. After removing the solvent from the ether layer, it was purified using a silica gel column to obtain the corresponding sulfoxide. IR (Neat) 306\2980, 292\166 people 1648, 158
5, 1478, 144 Table 1305 (SO2), 1147
(SO2), 1083.1038 (SO), 74&6a-1 NMR (δ, CDCl3) 1.47 (S..3H..CH3) 1.44-1.88 (M..2H,.CH3) 1 .64
(D..J=1.5Hz,.31(,CH3)1.92
-2.20 (M..2H., CU2-C=C)2.

26-2.52 (MllH..CH) 2.68-. 36(M,.4H.,Cdan.-SO-&C
Dan.

-SO2-) 5.41 (ratio, 1H..C = C)

Claims (1)

[Claims] 1 Substituted cyclohexene derivative represented by the following formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ Substituted cyclohexene derivative represented by (I) [R^1 and R^2 in formula (I) are each substituted n represents a phenyl group, n represents 0 or 1, and a dotted line represents the presence of a double bond at one of the positions indicated by the dotted line]. 2 The compound represented by the following formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) is ring-closed in the presence of an acidic catalyst, and if desired, the thio group in the product is oxidized to a sulfinyl group. Characteristic formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ Process for producing substituted cyclohexene derivatives represented by (I) [R^1 and R^2 in formulas (I) and (II) are each unsubstituted] n represents an optional phenyl group, n represents 0 or 1, and a dotted line in formula (I) represents the presence of a double bond at one of the positions indicated by this.