KR850000924B1 - Process for preparing epoxides from unsaturated hydrocarbons by regioselective expoxidations - Google Patents

Abstract

Epoxy compound is prepared from unsaturated hydrocarbons (I) and nitrobenzene sulfonyl chloride by means of reaction with peroxide (II) of which formula is RO2 in the presence of organic solvent such as acetonitrile under -20 - -35≰C temperature below the melting point; where R = sodium or potassium. (I) is 1,8-p-mentadiene, p- menta-6,8-diene-2-on, 4-(2,6,6-trimethyl-2cyclohexenyl)-butyn-2-on, 4-(2,6,6-trimethyl-1-cyclohexenyl)butyn-2-on, 5-vinyl-2-norborene, 1,1-diphenyl ethylene, 1,2-diphenyl ethylene, or benzal acetophenone.

Description

Selective Epoxide Preparation of Unsaturated Hydrocarbons

The present invention relates to a new and advanced process for producing epoxy compounds by reacting unsaturated hydrocarbon compounds with peroxides selectively. More particularly, the present invention relates to a method for preparing an epoxy compound by adding nitro benzenesulfonyl chloride to a superoxide in an unsaturated hydrocarbon compound. Epoxidation is the synthesis of various epoxides, which are important intermediates for the synthesis of pharmaceuticals, pesticides, and other natural products. Therefore, much research has been conducted to manufacture such epoxides more easily and at a lower cost. However, in particular, since epoxides used in high-grade natural product synthesis are compounds containing many other functional groups, there is an urgent need for a reaction system that selectively oxidizes only the desired double bonds and converts them into epoxides without damaging such highly reactive functional groups. come. The present invention is a mild reaction system capable of meeting these demands, which is represented by the following reaction.

R ₁ in the formula (I) represents a nitro (—NO ₂ ) group located at ortho, para, or meta of the benzene ring, and R in the formula (II) represents sodium or potassium, and the formulas (III) and ( ⅳ) R and R ₁ are the same as R of formula (I) R ₁ and the following structural formula (ⅱ) of at. The biochemical, physical, and chemical properties of superoxides (RO ₂ ), called "superoxides," have been studied in the past for about 20 years, but few are used for organic synthesis. In recent years, however, studies on the reactivity with simple organic compounds have been actively conducted. The present invention provides a new interesting reaction system using intermediates such as II under particularly mild reaction conditions using the radical nature and basicity of such superoxide. I think. Compounds having a double bond epoxidized by the above method are as follows. First, benzal acetophenone (chalcone), 1,2-diphenylethylene, 1,1-diphenylethylene, P-menta-6,8-diene-2-silver (1-carvone), 1.8-P-mentadiene ( limonene), 5-vinyl-2-norbornene, 4- (2,6,6-trimethyl-2-cyclohexenyl) butyn-2-one (α-Ionone). And 4- (2,6,6-trimethyl-1-cyclohexenyl) -butyn-2-one ((beta) -Ionone) etc. can be applied also to the compound which has a simple double bond.

Other methods used to oxidize one or more compounds having one or more double bonds to their corresponding epoxides are as follows.

end. Epoxidation Method Using Hydrogen Peroxide

This method is a common generalized epoxidation method using potassium hydroxide and sodium hydroxide as bases. However, the limitation of this method is mainly used to oxidize unsaturated ketones in the α, β-position, so when epoxidizing a compound having a normal isolated double bond, a mixture of monoepoxide and diepoxide is formed. Even more disadvantageous. Therefore, when epoxidizing only a double bond at a certain position, the yield is low and there is difficulty in separation, which is not a preferable manufacturing process.

I. Epoxidation Method Using Peroxy-acid

Peracetic acid, metachloroperbenzoic acid (MCPBA), etc. are commonly used as peroxide acid, and the temperature condition is 0 ℃ or higher or higher. It is difficult to use in the compound.

For example, 1,8-P-mentadiene was reacted for 30 minutes at 125 ° C. using peraceic acid or metachloroperbenzoic acid to obtain an epoxide. Not fair at fair (See US Pat. No. 3,655,698 (1963), 3,924,894 (1975)). As another example, 4- (2,6,6-trimethyl-1-cyclohexenyl) -butyn-2-one (β-Ionone) is reacted with per-phthalic acid at 0 ° C. and corresponding epoxy Sides were obtained, yielding 60% and by-products of diepoxide, which is also not good for manufacturing (see Helv. Chim. Acta., 29, 1829 (19 46)).

However, the present invention has a great advantage that the reaction conditions, such as a temperature of -20 ° C. to -35 ° C., are gentle, unlike the known manufacturing methods, and the reaction time is very short, and only the desired epoxide can be selectively obtained and the yield is also high. It is highly suitable for the epoxidation of compounds with complex structures, and the post-reaction treatment is simple for easy product separation. That is, the product is obtained by adding water, followed by extraction with chloroform or ether and then removing the solvent.

The present invention will be described in more detail when 1 mole of nitrobenzene sulfonyl chloride (Ia) represented by Structural Formula (I) is reacted at -20 ° C. to -35 ° C. under acetonitrile solvent with RO ₂ , which is a 3 mole excess oxide. Within 6 hours, the nitro benzene sulfonate represented by the formula (IV) together with the product epoxide is obtained quantitatively. By the way, it is presumed that intermediates in the form of structural formula (III) form during the reaction, and the intermediates play a role in attacking double bonds and converting them into epoxides. With superoxide used as described above as well as KO ₂ N _a O ₂ can also be used, nitrobenzene sulfonyl chloride in the ortho-addition to using the nitrobenzene sulfonyl chloride, p-nitrobenzene sulfonyl Chloride, meta-nitrobenzene sulfonyl chloride may also be used. In terms of yield, however, the ortho position was superior to the para or meta position in terms of yield. For example, when the benzal acetophenone (chalcone) is used as the olefin, the result is 84% for ortho, 75% for para and 60% for meta, which is better for ortho. In the case of l-carvone or limonene, ortho-nitrobenzenesulfonyl chloride also has better results than para-nitrobenzene sulfonyl chloride, so that the nitro group is substituted at the ortho position. In this case, it is assumed that the peroxide intermediate of the structural formula (IV) is more stable than para- or meta-substituted.

In particular, according to this method, 1,8-P-methadiene (1), P-menta-6,8-dien-2-one (2), 4- (2,6,6-trimethyl-2 cyclohexyl Yl) -butyn-2-one (3), 4- (2,6,6-trimethyl-1-cyclohexenyl) -butyn-2-one (4), and 5-vinyl-2-norbornene ( In the compound having two double bonds such as 5), the effect is greatly utilized to selectively epoxidize one double bond.

In the case of the compound having a double bond as described above, it can be seen that the double bond on the ring is oxidized to be an epoxide, and the other double bond is not oxidized, and the compound having a keto group unsaturated at the α, β-position. The double bond remains intact, and only the other double bond is oxidized, so that the peroxide intermediate represented by the formula (III) does not have the nature of anion and the Michael type addition reaction does not occur. It is assumed that an electron-responsive attack occurs and the reaction proceeds.

The following examples will illustrate the invention in more detail, but are not intended to limit the scope of the invention.

Example 1

Preparation of 1,2-epoxy-1,8-P-mentadiene (1 ').

A solution of ortho-nitrobenzenesulfonyl chloride (221 mg, 1.0 mmol) dissolved in acetonitrile (2.5 ml) in potassium superoxide (KO ₂ ) (220 mg, 3.0 mmol) was slowly added at -35 ° C., followed by 1 , 8-P-mentadiene (1) (81.7mg, 0.6mmole) was added and stirred for 4,5 hours. The reaction mixture was filtered, extracted with chloroform, and then the solvent was removed to prepare 71.1 mg (yield 87%) of 1,2-epoxy-1,8-P-mentadiene.

'Hnmr (CDCI ₃ ) (δ); 2,97 (1H, epoxide, 1.3 (3H, Me, epoxide), 1.92 (3H), 1.60 (3H, Me, = C-), 4.75 (2H, = C-)

Example 2

Preparation of 8,9-epoxy-P-6,8-dien-2-one (2 ')

A solution of ortho-nitrobenzene sulfonyl chloride (221 mg, 1.0 mmol) in potassium superoxide (KO ₂ ) (22 mg, 3.0 mmol) in acetonitrile (2.0 ml) was added at −35 ° C., and after about 5 minutes, P -Menta-6,8-dien-2-one (2) (90 mg, 0.6 mmole) is added and stirred for 3.0 hours. The reaction mixture was filtered, extracted with chloroform and the solvent removed to give 74.7 mg (83% yield) of 8,9-epoxy-P-menta-6,8-dien-2-one.

'H-nmr (CDCI ₃ ) (δ); 2,67 (2H, epoxide), 1.40 (3H, Me, epoxide), 6.7 (1H, = C-)

Example 3

Preparation of 4- (2,6,6-trimethyl-2,3-epoxy-2-cyclohexenyl) -butyn-2-one (3 ').

A solution of ortho-nitrobenzene sulfonyl chloride (221 mg, 1.0 mmol) in potassium superoxide (220 mg, 3.0 mmol) in acetonitrile (2.0 ml) was slowly added at -35 ° C and 4- (2,6,6- Trimethyl-2-cyclohexenyl) -butyn-2-one (3) (115 mg, 0.6 mmole) was added thereto, followed by stirring for 3.0 hours. The reaction mixture was filtered, extracted with chloroform and the solvent removed to give 97.7 mg (35% yield) of 4- (2,3-epoxy- (2,6,6-trimethyl-2-cyclohexenyl) -butyn-2- One was prepared.

○ UV: 225nm

'H-nmr (CDCI ₃ ) (δ); 3.0 (t, 1G, epoxide), 1.20 (3H, Me, epoxide), 1.0 (3H, Me, epoxyside), 1.0-2, 4 (5H), 0.9 (3H, Me), 1.0 (3H, Me), 2.2 (3H, Me) 5.92 (1H, -C = C-), 6.52 (1H, = C-CO-)

Example 4

Preparation of 4- (1,2-epoxy-2,6,6-trimethyl-1-cyclo hexenyl) -butyn-2-one (4 ')

A solution of ortho-nitrobenzene sulfonyl chloride (221 mg, 1.0 mmol) in acetonitrile (2.5 ml) in potassium excess product (KO ₂ ) (220 mg, 3.0 mmol) was added at -35 ° C, and 4- (2, 6,6-trimethyl-1-cyclohexenyl) -butyn-2-one (4) (115 mg, 0.6 mmole) was added thereto, followed by stirring for 2.5 hours.

The reaction mixture was filtered and extracted with chloroform, then the solvent was removed to give 96.6 mg (yield 84%) of 4- (1,2-epoxy-2,6,6-trimethyl-1-cyclohexenyl) -butyn-2- One was prepared.

○ UV: 228nm

'H-nmr (CDCI ₃ ) (δ); 1.0 (3H, Me, epoxide), 1.0-1.6 (6H), 2.17 (3H, Me, -CO-), 5.92 (1H, -C = C-), 6.52 (1H, = C-CO-)

Example 5

Preparation of 2,3-epoxy-5-vinyl norbornane (5 ').

A solution of ortho-nitrobenzene sulfonyl chloride (221 mg, 1.0 mmol) in acetonitrile (3.0 ml) was added to potassium superoxide (220 mg, 3.0 mmol), and 5-vinyl-2-norbornene (5) was added thereto. (72mg, 0.6mmole) is added and stirred for 5 hours. The reaction mixture was filtered, extracted with chloroform, and the solvent was removed to prepare 56.2 mg (yield 78%) of 2,3-epoxy-5-vinyl norbornane.

'H-nmr (CDCI ₃ ) (δ); 3.0 (2H, epoxyside), 0.75-1.80 (5H), 2.45 (2H), 4.85 (1H, -C = C-), 4.95 (1H, = C-CO-), 5.65 (1H, -C = C ―).

Example 6

Preparation of 1,2-epoxy-1,1-diphenylethane (6 ')

Slowly add a solution of ortho-nitrobenzenesulfonyl chloride (221 mg, 1.0 mmol) in acetonitrile (3.0 ml) to potassium superoxide (220 mg, 3.0 mmol) and add 1.1-diphenyl ethylene (7) (108 mg). , 0.6mmole) was added, followed by extraction with chloroform, and the solvent was removed to prepare 88.5 mg (yield 82%) of 1.2-epoxy-1,1-diphenylethane.

'H-nmr (CDCI ₃ ) (δ); 3.30 (2H, epoxide), 7.40 (10H, C ₆ H ₅ ―)

Example 7

Preparation of 1,2-epoxy-1,2-diphenylethane (7 ')

To a potassium superoxide (220 mg, 3.0 mmol) was added slowly a solution of ortho-nitrobenzenesulfonyl chloride (221 mg, 1.0 mmol) in acetonitrile (3.0 ml), and after about 5 minutes 1,2-diphenylethylene ( 6) (108mg, 0.6mmole) was added and stirred for 3 hours.

The reaction mixture was once filtered, extracted with chloroform and the solvent was removed to prepare 73.4 mg (yield 68%) of 1,2-epoxy-1,2-diphenylethane.

○ Melting Point: 65-66 ℃

'H-nmr (CDCI ₃ ) (δ); 3.80 (2H, epoxide), 7.30 (10H, C ₆ H ₅ ―)

Example 8

Preparation of Benzal Acetophenone Epoxide (8 ')

A solution of ortho-nitrobenzenesulfonyl chloride (221 mg, 1.0 mmol) in acetonitrile (3.0 ml) was slowly added to potassium superoxide (KO ₂ ) (220 mg, 3.0 mmol) and benzal acetophenone (8 mg) after about 5 minutes. ) (125mg, 0.6mmole) was added and stirred for 1.5 hours. Once the reaction mixture was filtered, extracted with chloroform and the solvent was removed to prepare 105 mg (84% yield) of Benzal acetophenone epoxide.

○ Melting Point: 88-89 ℃ C

'H-nmr (CDCI ₃ ) (δ); 4.0 (d, 1H), 4.10 (Cl 1H), 7.2-7.8 (10H, C6115-)

○ NaO ₂ (165mg, 3.0mmole)

Yield: 82% (101mg)

Example 9

Preparation of Benzal Acetophenone Epoxide (8 ')

A solution of ortho-nitrobenzenesulfonyl chloride (221 mg, 1.0 mmol) in acetonitrile (3.0 ml) was slowly added to sodium superoxide (NaO ₂ ) (165 mg, 3.0 mmol) and benzal acetophenone (8 mg) after about 5 minutes. ) (125mg, 0.6mmole) and stirred for 1.5 hours. Once the reaction mixture was filtered, extracted with chloroform and the solvent was removed to prepare 101 mg (yield 82%) of Benzal acetophenone epoxide.

○ Melting Point: 88-89 ℃

'H-nmr (CDCI ₃ ) (δ); 4.0 (d, 1H), 4,10 (Cl 1H), 7.2-7.8 (1H, C6115-)

○ NaO ₂ (165mg, 3.0mmole)

Yield: 82% (101mg)

Claims (3)

A process for preparing an epoxy compound by reacting an unsaturated hydrocarbon compound with nitrobenzenesulfonyl chloride and an excess oxide of formula (II) at a freezing point in the presence of an organic solvent. RO ₂ (Ⅱ) In the above, the unsaturated hydrocarbon compound refers to 1,8-P-mentadiene, P-menta-6,8-dien-2-one, 4- (2,6,6-trimethyl-2-cyclohexenyl) -butyne- 2-one, 4- (2,6,6-trimethyl-1-cyclohexenyl) -butyn-2-one, 5-vinyl-2-norbornene, 1,1-diphenylethylene, 1,2- Diphenylethylene or benzalacetophenone, wherein in formula (II) R is sodium or potassium. The method according to claim 1, wherein acetonitrile is used as the organic solvent. The method according to claim 1, wherein the reaction temperature is reacted at -20 ° C to -35 ° C.