JPS58201775A - Preparation of 3,4-dihydro-2h-benzopyran derivative - Google Patents

Abstract

PURPOSE:To obtain easily the titled compound useful as an intermediate for synthesizing optical active vitamin E and tocotrienol using inexpensively obtainable raw materials, by reacting hydroquinone (derivative) with a specific pyran derivative in the presence of a Lewis acid. CONSTITUTION:A compound shown by the formula I (R is H or protecting group; R<1> is H or alkyl; R<2> and R<3> are R<1>, alkoxy, or R<2> and R<3> are linked to form -CH=CH-CH=CH) is reacted with a 4-methyl-5,6-dihydro-2H-pyran shown by the formula II (one of X and Z is H and the other is linked to Y to form a bond) or 4-methylene-tetrahydropyran in the presence of a Lewis acid (e.g., aluminum chloride) in an amount to give 0.5-1.0 the molar quantity of the compound shown by the formula I at 0-100 deg.C, to give the desired compound shown by the formula III. USE:An organic acid ester of the desired compound is a stabilizer to the influence of light, heat and oxidizing agent for organic materials, especially synthetic resins.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a 3,4-dihydro-2H-benzobilane derivative represented by general formula (1).

In the above formula, R represents a hydrogen atom or a protective group.

As the protecting group, any commonly used protecting group may be used as long as it achieves the purpose of protecting a hydroxyl group, such as an acyl group such as an acetyl group, a propionyl group, a butyryl group, a methyl group, a t-butyl group, a tri-2- Examples include phenylmethyl group and benzyl group.

R1 represents a hydrogen atom or a lower alkyl group such as a methyl group, an ethyl group, a pro-, biyl, or butyl group. R2 and R3 are the same or different hydrogen atoms; methyl group, ethyl group,
It represents a lower alkyl group such as a propyl group or a butyl group; or a lower alkoxy group such as a methoxy group, an ethoxy group, a propoxy group, a butyl group, or a group such as R2 and a group 3.
Together they form a -CH=CH-CH=CH- group.

The 3,4-dihydro-2H-benzopyran derivatives represented by the general formula (1) are not only used as important synthetic intermediates for optically active vitamin E1 and optically active tocotriales by optically resolving them, but also for their organic Acid esters are useful as stabilizers for organic materials, especially synthetic resins, against the effects of light, heat, and oxidizing agents [Journal of the Society for Organic Synthesis and Chemistry 40, 268 (1982) and JP-A-14528-1983.
See Publication No. 3].

Conventionally, 3,4-dihydro-2H-benzobilane derivatives have been produced by reacting hydroquinone or its derivative with an alkenediol represented by the following formula or its monoether or monoester in the presence of a Lewis acid. (Unexamined Japanese Patent Publication No. 49-88876 and Japanese Unexamined Patent Publication No. 5
．． No. 6-145282! reference). However, the manufacturing cost of this method is not necessarily low, as the alkenediol and its derivatives used as raw materials are produced by Grignard reaction, and it is far from being an industrially advantageous method.

The present inventors conducted various studies in order to develop a method for producing 3,4-distal draw 2H-benzopyran derivatives using easily and inexpensively available raw materials, and found that 4-methyl-
3,4-dihydro-2H- using 5,6-dihydro-2H-pyran or 4-methylenetetrahydropyran as a raw material
discovered that benzopyran derivatives can be easily produced,
According to the present invention, it is represented by the general formula (II) OH [wherein R, R'', R2 and R8 have the same meanings as in the general formula (1)]. Hydroquinone or its derivatives and the general formula (
III) (In the formula, one of X and 2 is a hydrogen atom, and the other forms a bond together with Y.) is reacted with a pyran derivative represented by the following in the presence of a Lewis acid. -Possibly in one stage- 3,4- represented by the general formula (1)
- Dihydro-2H-benzopyran derivatives can be obtained.

4-Methyl-5,6-sihydro 2H used as raw material
-Pyran and 4-methylenetetrahydropyrane are produced in large amounts as by-products during the production of isoprene from isoptesy and formalin, and can also be synthesized by the reaction of tertiary-butanol with an aqueous formaldehyde solution in the presence of a non-acid catalyst. It can be easily and inexpensively obtained.

Examples of Lewis acids used in the present invention include boron trifluoride/ether complex, aluminum chloride, aluminum bromide, ferrous chloride, ferric chloride, stannous chloride, and ferric chloride.
Examples include tin, zinc chloride, sulfuric acid, and p-toluenesulfonic acid, but preferred are aluminum chloride and boron trifluoride/ether complex. The amount of Lewis acid used is 0.1 to 2 times, preferably 0.5 to 1.0 times, molar amount of the hydroquinone or its derivative represented by the general formula (II).

The condensation reaction in the present invention is preferably carried out in a solvent, such as 1,2-dichloroethane, dichloromethane, chloroform, 1,1,2-)lychloroethene, tetramide carbon 1. Halogenated hydrocarbons such as chlorobenzene; Hydrocarbons such as benzene, toluene, xylene, 6-cyclohexane, n-hexane, and ligroin; Nitrogen-containing compounds such as tromethane, nitrobenzene, benzonitrile, and acetonitrile; Methyl ethyl ketone, acetic acid Oxygen-containing compounds such as ethyl, butyl acetate, or mixtures thereof can be used as solvents, with 1,2-dichloroethane being particularly preferred. The amount of the solvent to be used is about 2 to 100 times the weight of the hydroquinone or its derivative represented by the general formula (I[), preferably about 5 to 20 times the weight.
It's twice as heavy. This condensation reaction is usually carried out at -140℃-T15
In a preferred embodiment of the present invention, the reaction is carried out at 0°C, preferably 03 to 100°C, by dissolving or suspending hydroquinone or its derivative represented by general formula (Il) and a Lewis acid in a solvent. While stirring and heating in an active gas atmosphere, about 0.5 molar amount of the bilane derivative represented by the general formula (1) is added to the hydroquinone represented by the general formula (I[) or a derivative thereof in an equivalent molar amount to 1 to 2 times the molar amount. ~8
Add and react over time. After adding the biran derivative represented by the general formula (nl), stirring is continued for about 0.5 to 4 hours to contain the 3,4-dihydro-2H-benzobilane derivative represented by the general formula (1). A reaction mixture is obtained.

The 3,4-dihydro-2H-benzopyran derivative can be separated and recovered from this reaction mixture by a conventional method. For example, by adding water to the reaction mixture, then extracting with ether, etc., washing the extract with water, drying, distilling off the solvent, and then vacuum distillation, a colorless to pale yellow viscous product can be obtained. A 3,4-dihydro-2H-benzopyran derivative represented by (1) can be obtained.

EXAMPLES The present invention will be specifically explained below with reference to Examples.

Example 1 Trimethylhydroquinoy 30.4t under nitrogen atmosphere
A mixture of 24.6 slJ of boron trisulfide/ether complex and 200 d of dichloroethane was heated to reflux, then 4-
23.5 t of methyl-5,6-cyhydro-2H-bilane 8- was added dropwise. After the dropwise addition, the reaction mixture was further heated under reflux for 1 hour, then cooled, water was added thereto, and then extracted with ether. After washing the extract with water and drying, low-boiling substances were distilled off, and the resulting concentrate was distilled under reduced pressure to obtain 3,4-dihydro-2-hydroxyethyl-2, which has the following physical properties. 5゜7,8-tetramethyl-2H
40.7 t of -benzobilan-6-ol (yield 81.
4%) Obtained 0 boiling point: 154-163 °C / 0.09 m
He1.2 (1m, 3H), 1.6-2.3
(m, 13H), 2.57 (t, J=7Hz,
2H), 3.85 (t, J=6Hz, 2H), 4.0
(br,s,2H,)Example 2 1.52v of trimethylino-ido-quinone under nitrogen atmosphere
b A mixture of ethane 10- and 4-9-methyl-5,6-cyhydro-2H-bilane and an equal amount of 4-methylenetetrahydrobilane was heated to reflux.1. Ot was added dropwise. After the dropwise addition, the mixture was further heated under reflux for 1 hour, and then 1 ml of the mixture was cooled, ice was added thereto, and the mixture was extracted with ether. After washing the extract with water and drying, low-boiling substances were distilled off, and the resulting concentrated liquid was placed in a glass tube oven (manufactured by Shibata Kagaku Kikai Kogyo Co., Ltd., bath temperature: 150-180°C.
3.4-dihydro-2-hydroxyethyl-2,5,7,8-tetramethyl-2H-benzobilan-6-ol was distilled at 2.06 f(
Yield: 82.4%) Example 3: .

Trimethylhydroquinone 1.522 under nitrogen atmosphere,
Aluminum chloride 0.67? A mixture of 4'-methyl-51, 6-dihydro-2H-bilane 1. Of10
- Dropped. After the dropwise addition, the reaction mixture was further heated under reflux for 1 hour, then cooled, water was added thereto, and then extracted with ether. After washing the extract with water and drying, low-boiling substances were distilled off, and the resulting concentrated liquid was heated in a glass tube oven (manufactured by Shibata Kagaku Kikai Kogyo Co., Ltd., bath temperature: 150~B) to 3,4-dihydride. 1.75 t of cr-2-hydroxyethyl-2,5,7,8-tetramethyl-2H-benzopyran-6-ol (yield: 74.2%) was obtained.0 Examples 4 to 12 In Example 3 Aluminum chloride 0.67f and 1,
Instead of 2-dichloroethane 101/, the predetermined amount of Lewis acid shown in the first page and the predetermined solvent IQj! 3,4-dihydro-2-hydroxyethyl-2,5,7,8'-tetramethyl-2H-
Benzopyran-61ol was obtained. The results are shown in Table 1.

Table 11-Example 13 1.94F of 4-acetoxy-2,3,5-)samethylphenol, 1.42F of boron trifluoride/ether complex and 10at of 1'',2-dichloroethane in a nitrogen atmosphere. 4-Methyl-5,6-sihydro-2H-pyran 1.Of was added dropwise to the mixture while heating to reflux. After the dropwise addition, the reaction mixture was further heated to reflux for 1 hour, then cooled, and water was added to it. , and then extracted with ether.The extract was washed with water and dried, and the low boiling point substances were distilled off, and the resulting concentrated solution was purified by silica gel column chromatography to obtain the following NMR spectrum. Suichi 6-ace!-jushi-3., 1 L 4-dihydro-2-hydroxyene-2.5.7.8
-Tetramethi-2H-benzopyrane2.1:M(
A yield of 76.613 was obtained.

1.22(s, 3)I); 1.46-2.13(m
, 13H) ;13-12-2.27(8,3H)i2.3-2.7(m,3H);
3-79 ('t, J' 7 H'z t 2 H)
Example 14 Except for using 4-benzyloxy-2,3,5-)limethylphenol 2,422 in place of 4-acetoxy-2,3,5-trimethylphenol 1.94F in Example 13, In the same manner as in Example 13, the following NM is obtained from □.
2.511% of 6-benzyloxy-3,4-dihydro-2-hydroxyethyl-2,5,7,8-tetra-methyl-2H-benzopyran with R spectrum (yield 7
Section 7.0) Obtained.

1.23. (a, 3H); 1.5.6-2.
7 (m, 16H>; 3.83 (t, J=7H
z, 2H) i4.66 (li, 2H) i7.
23-7.6 (m, 5H) 14- Example 15 A mixture of hydroquinone 1.10j', boron trifluoride/ether complex 1.42F and 1,2-dichloroethane 101111 was heated to reflux under a nitrogen atmosphere. 1.02 of 4-methyl-5,6-sihydro 2H-pilaf was added dropwise. After the dropwise addition, the reaction mixture was further heated under reflux for 1 hour, then cooled, water was added thereto, and then extracted with ether. After washing the extract with water and drying, low-boiling substances were distilled off, and the resulting concentrated liquid was distilled in an open glass tube to obtain 3,4-
dihydro-2-hydroxyethyl-2-methyl-2H-
Benzopyran-6-ol to 1.07F (yield 51.4
%)Obtained.

HMS.

NMR spectrum (9QMHz) δCD (Js'1.2
5 (s, 3H); 1.5-2.3 (m, 4H); 2.6
5 (t, J=7Hz, 2H); 3.6-4.0 (m,
2H); 4.4 (br, s, 2H); 6
．． 4 to 6.7 (mta:a) Example 16 Example 15 except that 2,3-dimethoxy-5-methyl-p-hydroquinone 1.84F was used instead of Hyde Mouth Non 1.1Of in Example 15. 3,4-dihydro-2- having the following NMR spectrum was obtained by performing the reaction and post-treatment in the same manner as above, and purifying the obtained concentrate by silica gel column chromatography.
Hydroxyethyl-7,8-dimethoxy-2,5-dimethyl-2H-benzopyran-6-ol with 1.46f (
Yield: 51.8%).

N M Rx He/Tok (90MHz) δHMS
.

CDα3゜1.27 (IS, 3) (); 1.5-2.3 (
m, 7H): 2.54 (t, J=7Hz, 2H)
i, a, a ~4. Q(m, 8H); 5.0(br
, s, 2H) Example 1r The reaction and post-treatment were carried out in the same manner as in Example 15, except that 2-methylnaphthoquinone 1.74F was used instead of hydroquinone 1.1Of, and the obtained concentrate was When purified by silica gel column chromatography, 3,4-dihydro-2-hydroxyethyl-2,5-dimethyl-2H-su7 (1,2-b
) biran-6-ol 1.28? (Yield 47.1 cm)
Obtained.

Patented wheat flour Kuraray Co., Ltd. Representative Patent Attorney Ken Honda 17-

Claims (1)

[Claims] (In the formula, R represents a hydrogen atom or a protective group, R1 represents a hydrogen atom or a lower alkyl group, R2 and R3 are the same as -
or differently represents a hydrogen atom, a lower alkyl group or a lower alkoxy group, or R2 and R3 together represent -C
Forms a H=CH-CH=CH- group. ). In the presence of a Lewis acid, hydroquinone or its derivative represented by the formula and a pyran derivative represented by A method for producing a 3,4-dihydro-2H-benzopyran derivative represented by the general formula (in the formula, R, R1, R2 and R3 are as defined above), which is characterized by carrying out the following reaction.