JPH0892151A - Production of allylquinone - Google Patents

Abstract

PURPOSE: To regioselectively and efficiently obtain the compound, concerned in electron transport, etc., in living bodies, having diverse physiological activities and useful as medicines, etc., without requiring the protection of carbonyl group by reacting an allyltrifluorosilane with a quinone. CONSTITUTION: This method for producing an allylquinone of formula III (R<1> to R<5> are each H, an alkyl, an aryl, an alkenyl, an alkoxy, cyano or a halogen; R<1> and R<2> , R<3> and R<4> , R<2> and R<5> or R<1> and R<3> , together with C to which they are respectively bound, may form a ring; R<6> to R<8> are each H, an alkyl, an aryl, an alkenyl, an alkynyl, an alkoxy, OH or R<6> and R<7> , together with C to which they are respectively bound, may form a ring) [e.g. 2-(3-methyl-2- butenyl)-1,4-benzoquinone] is to react an allyltrifluorosilane of formula I [e.g. (E)-2-butenyltrifluorosilane] with a p-quinone of formula II (X is H or a halogen) (e.g. 1,4-benzoquinone), preferably in the coexistence of an oxidizing agent.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention has the following general formula [III]

[Chemical 4] (In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a hydrogen atom, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, an alkoxy group, a cyano group or a halogen atom. ¹ and R ² , R ³ and R ⁴ , R ² and R ^5, or R ¹ and R ³ may be combined with the carbon atom to which they are bonded to form a ring, and R ⁶ , R ⁷ and R ⁸ are Each of them is independently a hydrogen atom, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, an alkoxy group or a hydroxyl group, and R ⁶ and R ⁷ can form a ring together with the carbon atom to which they are bonded. )
Relates to a method for producing allylquinone represented by:

[0002]

2. Description of the Related Art Allylquinones are known to be involved in electron transfer in vivo, oxidative phosphorylation or photosynthesis in plants, and exhibit various physiological activities such as blood coagulation ["The Chemistry of Quinoid Compound"
s ”Part.2, p683, Wiley, NewYork (197)
4)]. Particularly, physiologically active allylquinones such as vitamin K, coenzyme Q, and plastoquinone are useful as medicines.

As a conventional synthetic method of the allylquinone represented by the general formula [III], (1) a method of reacting an allyltin compound with a quinone in the presence of a trifluoroborane diethyl ether complex [J. Am. Chem. Soc. , 10
2, 3774 (1980); Org. Chem. , 45,
4097 (1980)], (2) a method of reacting a bisallylnickel complex with quinone [J. Am. Chem. Soc. , 1
00,3461 (1978))], (3) a method of reacting an allyl halide with quinone using zinc dust [Chem.
Lett. , 901 (1977)], (4) a method of reacting allyltrimethylsilane with quinone in the presence of titanium tetrachloride [Tetrahedron Lett. , 4041 (197)
7)], (5) A method of reacting allyl alcohol or allyl halide with quinone in the presence of an acid catalyst [J. Am. Che
m. Soc. , 61, 2559 (1939); Ibid. , 6
1, 3467 (1939); Ibid. , 62, 1982
(1940)], (6) A method in which a hydroxyquinone-protected hydroquinone is reacted with an allyl nickel compound and then oxidized [J. C. S. Perkin, 2289 (1973)].

However, all of these methods have the following drawbacks. That is, the method (1) requires the addition of a trifluoroborane diethyl ether complex and uses a toxic allyltin compound, and thus is not suitable as a method for synthesizing a drug. The method (2) has a drawback that the selectivity of the reaction is low and that an excessive amount of heavy metal complex is required. The method (3) has a low regioselectivity of the reaction and gives a plurality of products which are difficult to separate. The method (4) uses an allylsilicon compound as in the present invention, but uses titanium tetrachloride in a stoichiometric amount or more and has low reactivity of allyltrimethylsilane to be used for the synthesis of physiologically active quinone. It is not possible to introduce the required 3-methyl-2-butenyl group into the quinone. (Refer to Reference Example 1 below) In the method (5), since allyl alcohol and allyl halide are unstable, a side reaction occurs, the yield is low, and a large number of by-products are provided. In the method (6), hydroquinone having a protected hydroxyl group must be used for the purpose of protecting the carbonyl group of quinone, and the synthesis process is complicated.

[0005]

An object of the present invention is to provide an efficient process for producing allylquinone represented by the above general formula [III], which does not have such drawbacks.

[0006]

Means for Solving the Problems The present inventors have conducted investigations on a method for producing allylquinone, and as a result, by reacting allyltrifluorosilane with quinone, allylquinone represented by the general formula [III] is The present invention has been completed by finding that it can be obtained regioselectively without the need to protect the carbonyl group.

That is, the present invention has the following general formula [I]

[0008]

[Chemical 5]

(In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a hydrogen atom, an alkyl group, an aryl group, an alkenyl group, an alkoxy group, a cyano group or a halogen atom. ¹ and R ² , R ³ and R ⁴ , R ² and R ⁵ or R ¹ and R ³
Each may form a ring together with the carbon atom to which it is attached. ) The allyltrifluorosilane represented by the following general formula [II]

[0010]

[Chemical 6]

(Wherein R ⁶ , R ⁷ and R ⁸ are each independently a hydrogen atom, an alkyl group, an aryl group, an alkenyl group,
An alkynyl group, an alkoxy group, and a hydroxyl group. R ⁶ and R ⁷
Each may form a ring together with the carbon atom to which it is attached. X represents a hydrogen atom or a halogen atom. ), And a method for producing allylquinone represented by the above general formula [III], which comprises reacting p-quinone represented by

The allyltrifluorosilane represented by the above general formula [I] used in the present invention is an allyltrichlorosilane [J. Organomet. Chem. , 96, C1 (197
5)] is easily fluorinated with antimony trifluoride [Organometaliics, 5, 1490 (1
986)].

As allyltrifluorosilane, for example, (E) -2-butenyltrifluorosilane, (Z)
-2-butenyltrifluorosilane, (3-methyl-2
-Butenyl) trifluorosilane, [(E) -3-phenyl-2-propenyl] trifluorosilane, (2-methyl-2-propenyl) trifluorosilane, (1-methyl-2-butenyl) trifluorosilane, [(E)-
3-fluoro-2-propenyl] trifluorosilane,
[(E) -3-Methoxy-2-propenyl] trifluorosilane, [(E) -3-Cyano-2-propenyl] trifluorosilane, (2-phenyl-2-butenyl) trifluorosilane, [(E ) -3-Methoxy-2-propenyl] trifluorosilane, [(E) -3-chloro-
2-propenyl] trifluorosilane, geranyltrifluorosilane, farnesyltrifluorosilane, phytyltrifluorosilane, 2,4-pentadienyltrifluorosilane, cyclohexen-2-ylmethyltrifluorosilane, 2- (cyclopentyl Ridene) ethyltrifluorosilane, 1-methylcyclohexen-3-yltrifluorosilane and the like can be used.

The other raw material, p-quinone represented by the above general formula [II], is a compound that can be easily synthesized and is industrially easily available. In the formula of the general formula [II], R ⁶ , R ⁷ , and R
⁸ includes a hydrogen atom, an alkyl group, an alkenyl group,
An alkynyl group, an aryl group, an alkoxy group and a hydroxyl group can be used. Specifically, for example, 1,4-benzoquinone, 2,3-dimethyl-1,4-benzoquinone,
2,5-dimethyl-1,4-benzoquinone, 2,3-diethyl-1,4-benzoquinone, 2-methyl-3-hexyl-1,4-benzoquinone, 2-methyl-1,4-benzoquinone, 2- Octyl-1,4-benzoquinone, 2,3,
6-trimethyl-1,4-benzoquinone, 2-hydroxy-6-methyl-1,4-benzoquinone, 2-hydroxy-5-methyl-1,4-benzoquinone, 2-ethoxy-1,4-benzoquinone, 3- Decanoxy-1,4-benzoquinone, 2,3-dimethoxy-6-methyl-1,4-benzoquinone, 5-bromo-2,3-dimethoxy-6-methyl-1,4-benzoquinone, 2,3-dimethoxy- 1,
4-benzoquinone, 2-pentyloxy-6-methoxy-1,4-benzoquinone, 2-phenyl-1,4-benzoquinone, 2- (4-methylphenyl) -1,4-benzoquinone, 2- (3-chlorophenyl ) -1,4-Benzoquinone, 2-ethynyl-1,4-benzoquinone, 2-phytyl-1,4-benzoquinone, 2-geranyl-1,4-
Benzoquinone, 1,4-naphthoquinone, 2-methyl-1,
4-naphthoquinone, 2-methyl-3-bromo-1,4-
Naphthoquinone, 2-bromo-1,4-naphthoquinone, 2
-Methyl-3-chloro-1,4-naphthoquinone, 2-methyl-3-iodo-1,4-naphthoquinone, 2-methoxy-1,4-naphthoquinone, 2-ethenyl-1,4-naphthoquinone, 2-phenyl -1,4-naphthoquinone, 2-
Hydroxy-1,4-naphthoquinone, 7,8,9,10
-Tetrahydro-1,4-naphthoquinone and the like can be used.

As the halogen atom represented by X,
Chlorine atom, bromine atom or iodine atom can be preferably used.

The method of the present invention is preferably carried out in a solvent from the viewpoint of reaction efficiency. For example, formamide, N, N-dimethylformamide, N, N-dimethylacetamide,
An amide solvent such as N, N-dimethylimidazolidinone and hexamethylphosphoric triamide, dimethyl sulfoxide, tetrahydrofuran (THF), dioxane, acetonitrile, diethyl ether and the like can be used alone or in combination. The reaction can be carried out in the range of 0 to 120 ° C., but from the viewpoint of reaction efficiency, it is room temperature to 10 ° C.
It is desirable to carry out at 0 ° C.

In the present invention, X is a hydrogen atom,
Since hydroquinone is by-produced when an oxidizing agent does not coexist, it is preferable to use p-quinone in an amount twice that of allyltrifluorosilane.

Particularly when X is a hydrogen atom, when the method of the present invention is carried out in the presence of an oxidant, the production of by-product hydroquinone is suppressed, resulting in an improvement in reaction efficiency and a product allylquinone. The yield of sucrose is significantly increased [see Examples 7 and 8]. As the oxidizing agent that can be used, an oxidizing agent that can oxidize hydroquinone can be used, and examples thereof include ferric chloride and silver oxide. The oxidizing agent is preferably used in an equimolar amount or more with respect to p-quinone and used in an amount of 2 equivalents or more.

[0019]

EXAMPLES The present invention will be described in more detail with reference to Examples and Reference Examples. However, the present invention is not limited to them.

Example 1

[0021]

[Chemical 7]

1,4-benzoquinone (32.7 mg,
0.30 mmol) and (3-methyl-2-butenyl) trifluorosilane (23.1 mg, 0.15 mm
ol) in formamide solution (1.0 ml, distilled from sodium sulfate, the same applies below) at room temperature in an argon atmosphere.
It was stirred for 68 hours. Water was added to the reaction solution and extracted with ether. After the organic layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure, and the crude product obtained was purified by column chromatography (ethyl acetate: hexane = 1: 2) to give 2- (3-methyl-2). -Butenyl) -1,4
-14.3 mg of benzoquinone was obtained (0.081 mmo
1, yield 54%, yield depending on the amount of silane used).

¹ H-NMR (CDCl ₃ ): δ1.64
(S, 3H), 1.77 (s, 3H), 3.12 (d,
J = 7.1 Hz, 2H), 5.15 (t, J = 7.1H
z, 2H), 6.54 (q, J = 2.0Hz, 1H),
6.65-6.80 (m, 2H) IR (neat): 1
655, 1607, 1300, 900 cm ^-1

Example 2

[0025]

Embedded image

1,4-benzoquinone (32.7 mg,
0.30 mmol) and [(E) -2-butenyl)]
Formamide solution (1.0 ml) of trifluorosilane (21 mg, 0.15 mmol) in an argon atmosphere,
Stir at room temperature for 68 hours. Water was added to the reaction solution and extracted with ether. The organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product, which was subjected to column chromatography (ethyl acetate: hexane = 1: 2).
2-[(E) -2-butenyl)]-
10.4 mg of 1,4-benzoquinone was obtained (0.062
mmol, yield 41%, yield depends on the amount of silane used).

¹ H-NMR (CDCl ₃ ): δ1.71
(D, J = 6.1 Hz, 3H), 3.10 (d, J =
6.4 Hz, 2H, 5.47 (dt, J = 15.2,
6.4 Hz, 1 H), 5.56 (dq, J = 15.2,
6.1 Hz, 1 H), 6.57 (q, J = 2.1 Hz,
1H), 6.66-6.77 (m, 2H) IR (neat): cm ^-1

Example 3

[0029]

[Chemical 9]

2,3-dimethoxy-5-methyl-1,4-
Benzoquinone (165 mg, 0.91 mmol) and (3-methyl-2-butenyl) trifluorosilane (7
1 mg, 0.46 mmol) formamide solution (2.
(0 ml) was stirred for 68 hours at room temperature in an argon atmosphere. Water was added to the reaction solution and extracted with ether. The organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product, which was purified by column chromatography (ethyl acetate: hexane = 1: 2).
(3-Methyl-2-butenyl) -2,3-dimethoxy-
6-methyl-1,4-benzoquinone (coenzyme Q) 31.
6 mg was obtained (0.126 mmol, yield 28%, yield depends on the amount of silane used).

¹ H-NMR (CDCl ₃ ): δ1.68
(S, 3H), 1.74 (s, 3H), 2.02 (s,
2H), 3.18 (d, J = 7.1Hz, 2H), 3.
98 (s, 3H), 4.00 (s, 3H), 4.94
(T, J = 7.1 Hz, 1 H) IR (neat): 2950, 1660, 1650, 1
615,1265 cm ^-1

Example 4

[0033]

[Chemical 10]

2,3-Dimethyl-1,4-benzoquinone (40.8 mg, 0.30 mmol) and (3-methyl-2-butenyl) trifluorosilane (23.1 m)
g, 0.15 mmol) in formamide solution (1.0 m
l) was stirred at room temperature in an argon atmosphere for 68 hours.
Water was added to the reaction solution and extracted with ether. The organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product, which was purified by column chromatography (ethyl acetate: hexane = 1: 10).
-Methyl-2-butenyl) -2,3-dimethyl-1,4-
16.3 mg of benzoquinone (plastoquinone) was obtained (0.080 mmol, yield 53%, yield depends on the amount of silane used).

¹ H-NMR (CDCl ₃ ): δ1.37
(S, 3H), 1.75 (s, 3H), 2.01 (s,
3H), 2.03 (s, 3H), 3.11 (d, J =
7.3 Hz, 2 H), 5.15 (t, J = 7.3 Hz,
1H), 6.47 (s, 1H) IR (neat): 2980, 2940, 2875, 1
730, 1650, 1620, 1450, 1380, 1
320, 1300, 1265, 1240, 1100cm
^-1

Example 5

[0037]

[Chemical 11]

2-Bromo-3-methyl-1,4-naphthoquinone (25.1 mg, 0.10 mmol) and (3
-Methyl-2-butenyl) trifluorosilane (77m
g, 0.50 mmol) with formamide (1.0 ml)
In a mixed solvent of / tetrahydrofuran (0.2 ml), the mixture was stirred at 80 ° C under an argon atmosphere for 62 hours. Water was added to the reaction solution and extracted with ether. The organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product, which was subjected to column chromatography (ethyl acetate:
When purified with hexane = 1: 4), 3-methyl-2-
13.0 mg of (3-methyl-2-butenyl) -1,4-naphthoquinone (vitamin K ₁ ) was obtained (0.054 mm
ol, yield 54%, yield depending on the amount of naphthoquinone used).

¹ H-NMR (CDCl ₃ ): δ 1.69
(S, 3H), 1.80 (s, 3H), 2.20 (s,
3H), 3.36 (d, J = 7.0Hz, 2H), 5.
01 (t, J = 7.0 Hz, 1H), 7.63-7.7
2 (m, 2H), 8.02 to 8.13 (m, 2H) IR (neat): 2975, 2940, 2875, 1
730, 1660, 1600, 1380, 1300, 1
290,720 cm ^-1

Example 6

[0041]

[Chemical 12]

1,4-naphthoquinone (47.8 mg,
0.30 mmol) and (3-methyl-2-butenyl) trifluorosilane (23 mg, 0.15 mmo
l) was stirred in a formamide (1.0 ml) solvent under an argon atmosphere at room temperature for 12 hours. Water was added to the reaction solution and extracted with ether. The organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product, which was subjected to column chromatography (ethyl acetate: hexane =
When purified by 1: 2), 18.6 mg of 2- (3-methyl-2-butenyl) -1,4-naphthoquinone was obtained (0.082 mmol, yield 55%, yield depends on the amount of silane used). .

¹ H-NMR (CDCl ₃ ): δ1.67
(S, 3H), 1.79 (s, 3H), 3.28 (d,
J = 7.4Hz, 2H), 5.23 (t, J = 7.4H
z, 1H), 6.77 (t, J = 1.5Hz, 1H),
7.72 (d, J = 5.8 Hz, 1H), 7.73
(D, J = 5.8 Hz, 1H), 8.06 (dd, J =
5.8, 3.3 Hz, 1H), 8.10 (dd, J =
5.8, 3.3 Hz, 1H) IR (neat): 3080, 2930, 1730, 1
670, 1620, 1600, 1335, 1305, 1
670, 1270, 1250 cm ^-1

Example 7

[0045]

[Chemical 13]

1,4-naphthoquinone (46.3 mg,
0.29 mmol) and (3-methyl-2-butenyl) trifluorosilane (228 mg, 1.46 mmo
1) and ferric chloride hexahydrate (791 mg, 2.93)
(mmol) in a formamide (1.5 ml) solvent at room temperature under an argon atmosphere for 63 hours. Water was added to the reaction solution and extracted with ether. After the organic layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure, and the crude product obtained was purified by column chromatography (ethyl acetate: hexane = 1: 4) to give 2- (3-methyl-2).
63.0 mg of -butenyl) -1,4-naphthoquinone was obtained (0.278 mmol, yield 96%, yield depends on the amount of naphthoquinone used). The product spectrum is shown in Example 6.
In agreement with the one obtained in.

Example 8

[0048]

Embedded image

2,3-Dimethyl-1,4-benzoquinone (40.8 mg, 0.30 mmol) and (3-methyl-2-butenyl) trifluorosilane (114 mg,
0.73 mmol) formamide solution (1.5 ml)
And ferric chloride hexahydrate (161 mg, 0.60 mm
ol) was stirred at room temperature for 12 hours in an argon atmosphere. Water was added to the reaction solution and extracted with ether. The organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product, which was purified by column chromatography (ethyl acetate: hexane = 1: 10).
(3-methyl-2-butenyl) -2,3-dimethyl-1,
56.8 mg of 4-benzoquinone (plastoquinone) was obtained (0.279 mmol, yield 93%, yield depends on the amount of benzoquinone used). The product spectrum is shown in Example 4.
In agreement with the one obtained in.

Reference Example 1

[0051]

[Chemical 15]

Reference [Tetrahedron Lett. , 4041
(1980)], it was difficult to introduce a 3-methyl-2-butenyl group into quinone, and the following experiment was conducted. That is, according to the method described in the literature,
1,4-naphthoquinone (47.8 mg, 0.30 mmo
l) and (3-methyl-2-butenyl) trimethylsilane (23 mg, 0.15 mmol) in dichloromethane solvent titanium tetrachloride (57 mg, 0.30 mmol).
The reaction was carried out in the coexistence with the above from −78 ° C. to room temperature for 3 hours, but no product was obtained and the raw material quinone was recovered.

─────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] June 29, 1995

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0012

[Correction method] Change

[Correction content]

The allyltrifluorosilane represented by the above general formula [I] used in the present invention is an allyltrichlorosilane [J. Organomet. Chem. , 96, C1 (197
5)] are readily obtained by fluorination by the antimony trifluoride [Organometal l ics, 5,1490 (1
986)].

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication C07C 253/30 255/40

Claims (2)

[Claims] 1. The following general formula [I]: ^{(Wherein, R 1, R 2, R} 3, R 4 and R ⁵ each are independently hydrogen atom, an alkyl group, an aryl group, an alkenyl group, an alkoxy group, .R ¹ is a cyano group or a halogen atom
And R ² , R ³ and R ⁴ , R ² and R ^5, or R ¹ and R ³ may form a ring together with the carbon atom to which they are bonded. ) And allyltrifluorosilane represented by the following general formula [I
I] (In the formula, R ⁶ , R ⁷ and R ⁸ are each independently a hydrogen atom,
An alkyl group, an aryl group, an alkenyl group, an alkynyl group, an alkoxy group, and a hydroxyl group. R ⁶ and R ⁷ may together with the carbon atom to which they are bound form a ring. X represents a hydrogen atom or a halogen atom. ) Represented by the following general formula [III]: (In the formulae, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸
Represents the same meaning as above). 2. The method for producing allylquinone according to claim 1, which comprises reacting in the presence of an oxidizing agent.