JPS58103328A - P-prenylstyrene and its preparation - Google Patents

Abstract

NEW MATERIAL:p-Prenylstyrene[synonym: 1-(3-methyl-2-butenyl)-4-ethenylbenzene]. USE:Intermediate of 2-(p-prenylphenyl)propionic acid and its salt (antiphlogistic and analgesic agent having extremely low effect to cause digestive tract disorders). PROCESS:p-Prenylstyrene can be prepared by reacting (A) a Grignard reagent derived from the compound of formula (Z<1> is prenyl or vinyl; X<1> is halogen) and metallic magnesium with (B) the compound of formula Z<2>-X<2> (where Z<1> is prenyl, Z<2> is vinyl, and when Z<1> is vinyl, Z<2> is prenyl; X<2> is halogen), if necessary in the presence of (C) a catalyst comprising a compound of the VIII-group metal of the periodic table.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to p-prenylstyrene and a method for producing the same.

p-prenylstyrene [also known as 1] provided by the present invention
-(3-Methyl-2-butenyl)-Mato-ethynylbenzene] is a new compound that has not been described in any known literature.2-( It is useful as an intermediate for the production of p-phrenylphenyl)furopionic acid and its att-.

Conventional* 2-(p-prenylphenyl)furopionic acid has been produced using a ketal of p-haloacetophenone as a starting material and a six-step process (41 Kai 1@
54-1ff3545) is known, but
This method requires expensive raw materials and long steps, and is not necessarily suitable for industrial implementation.

The present inventors have conducted intensive studies on a method for producing 2-(P-prenylphenyl)furopionic acid using a short reaction process using raw materials that can be obtained industrially, and have found that p-prenylphenyl styrene is industrially easy to produce. The present inventors have discovered that scales can be obtained from available raw materials in a short reaction process and lead to 11JIK2-(P-prenylphenyl)furopionic acid, and have completed the present invention.

That is, according to the present invention, the following method +1), tt
+ and 611) p-grenylsterene can be produced.

Method (1) D. A Grignard reagent obtained from a compound represented by the general formula % (1) (in the formula *Z"Fi prenyl group or vinyl group f: %X1 represents a halogen atom tube) and metallic magnesium. tube, if necessary, in the presence of a metal compound catalyst of Recommended Group 1 of the Periodic Table, to convert the general formula 2 (%) (in the formula, z3 is Ktj when the above z1 is a prenyl group
It represents a vinyl group, and when the above z1 is a vinyl group, it represents a prenyl group, and X3 represents a halogen atom. ) A method of reacting with a compound shown in

Method (il) General formula %formula% () (In the formula, one of 11 and RIFi represents a hydroxyl group.

The other represents a water bulk atom. ) Method O (lii) of dehydrating the compound shown in
) General formula % Formula % (1) (In the formula, one of XI and X4Fi is a 7'' halogen atom.

It represents an arylsulfonyl group or an alkyl group, and the other represents a hydrogen atom. ) Salt to the compound shown by! ! Method O (1)
) Among the compounds represented by the general formula (1) used in P + 7% losterene, P
A method of reacting a Grignard compound obtained from p-bromochlorobenzene and metallic magnesium with vinyl chloride in the presence of a nickel salt catalyst (K, Tamao a
tal, Bull@tin of th@Ch@m
1ca18ociety of Japan, Vol.
, 49(7)*1Q58-1969 (1976)] etc. 011 p-I
V Nylhalobenzene tL IIJL Ha.

The two halogen atoms of bhp-dihalobenzene are either the same or different from each other. , W, bromine atom, chlorine atom, or fluorine atom, but from the viewpoint of industrial availability, bromine atom or chlorine atom is preferable as metal madanesium #i, Grignard Preferably, a piece of magnesium is used for the reaction, but powdered or granular magnesium, or active magnesium prepared from magnesium chloride and potassium metal may also be used. Prenyl halides include prenyl chloride and prenyl bromide. Preferably 0 It is preferable to use a solvent in carrying out this reaction.

In particular, tetrahydrofuran, tetrahydrofuran, diethyl ether, diisopropyl ether.

Ethers such as dimethoxyethane! Use of solvents is recommended. Try Grignard! Generally speaking, the reaction temperature during production can be arbitrarily selected within the range of about -20°C to about 160°C, but it is easier to control the reaction temperature by refluxing the solvent. It is preferable because there is. Magnesium metal is usually used preferably in an amount of about 1 to 1.5 atomic amounts relative to p-dihalobenzene. The reaction temperature in the reaction of the Grignard reagent with the prenyl halide can range anywhere from about -30°C to about 100°C.

The reaction can also be accelerated by the addition of a zero steel catalyst, a nickel catalyst, etc., preferably at a temperature of about 0.degree. C. to about 30.degree.

The amount of prenyl halide to be used is approximately 2 moles per ftp-dihalobenzene used when preparing the Grignard reagent.
In the method (:) where p-halostyrene is used as the compound represented by the general formula (1) and prenyl halide is used as the compound represented by the general formula (1), Ktj,
Preparation of a Grignard reagent from p-halostyrene and metallic magnesium and reaction between the scissors Grignard reagent and prenyl halide Fi, when preparing a Grignard reagent from the above-mentioned p-dihalobenzene and metallic magnesium and reacting it with prenyl halide This can be done using the same operations and conditions as . As p-no10 styrene, p-chlorostyrene and p-bromstyrene are preferred.

In method (11), using p-prenylhalobenzene as the compound represented by general formula (1), general formula (II)
Even when vinyl rogenide is used as the compound represented by..., the reaction is preferably carried out in the presence of a FiS medium, particularly in the presence of an ether solvent such as tetrahydrofuran, tetrahydropyran, diethyl ether, diisopropyl ether, dimethoxyethane, etc. It is preferable to use Reaction temperature KFi for preparing Grignard reagent II from p-prenylno-lobenzene and metallic magnesium: from about 0°C to about 16°C
Although the temperature can vary arbitrarily within the range up to 0°C, it is preferable to reflux sm to control the reaction IL [f: 0 because the operation is simple.To start the reaction, a small amount of iodine, ethyl bromide, It is effective to activate magnesium by adding dicared ethylene, etc.

The amount of magnesium metal to be used is preferably about 1 to 4 J1 per p-greel halobenzene.The reaction between the Grignard reagent and vinyl 10genide is carried out using a metal compound from Group I of the periodic table. carried out in the presence of It is preferable to use Fi, vinyl chloride, or vinyl bromide as the vinyl halide, and the amount used is generally about 7 molar to about 3 times the mole of p-prenyl/10 benzene used in preparing the Grignard reagent. Examples of effective examples of metal compounds of group Ⅰ of the periodic table used as catalysts include nickel compounds, iron compounds, badge ram compounds, etc.
Specific examples include NiC15 and NiBr5.

N1 (aaac% (aeae represents an acetylacetonate group).

Ni ((Cs)b)a P )+C1m, Ni
[(Cakh)I P(CI&)*P(C5Hs
)1] CIs.

etc. The happy group metal compound catalyst #i, which takes 0, depends on the type 111tc4, but generally, it is about 0.0014 l to about It is used in amounts within the range of lθ molar. The reaction temperature is about -60℃60
40° C. to about .° C., preferably about −30° C. to about .

The compound represented by general formula (1) used in method (11) (Sh 1-Cp-brenylphenyl) ethanol is purified by p-ethanol according to a method previously discovered by some of the present inventors and their co-researchers. j6 (41111856-1
34778 and 56-134779), and 2-(p-brenylphenyl)ethanol can be easily prepared by reacting ethylene oxide with a Grignard reagent obtained from p-prenylhalobenzene and metallic magnesium. These x-Cp-
Frenyl) Phenylethanol! It is possible to obtain tp-prenylstyrene by subjecting H2-(II-prenylphenyl)ethanol to dehydration xt. This dehydration reaction converts the 1111 or secondary alcohol into the corresponding olefinic compound. Dehydration reaction methods and conditions known to be useful for the conversion can be used. For example, Keokalu v view (Ch@m1
cal Revi@w) Volume 45 No. 347-383
(1949) can be used. However, in order to avoid undesirable rigid reactions such as double bond migration or polymerization reactions, it is preferable to carry out the dehydration reaction under as mild conditions as possible. The alcohol is mixed with about 0.1 to 50% by weight of acidic potassium sulfate to the alcohol in an inert solvent such as hexane, benzene, toluene, etc., at a temperature of about 0°C to about 200°C. A heating method is particularly suitable.

The compound represented by the general formula (P/) used in method (iiD) is a compound represented by the general formula (P/), a halogenating agent such as phosphorus halide, thionyl chloride, arylsulfonyl ha2)'-! It can be easily obtained by combining &H alkanesul with nylhatenyl halide. General formula (P
When Xst or X4 represents a halogen atom, the /%Q gen atom is preferably a chlorine atom or a bromine atom. It was. When Xt or X4 represents an arylsulfonyloxy group.

The arylsulfonyloxy group is preferably a benzenesulfonyloxy &, P-)luenesulfonyloxy group,
α-mata is a β-naphthalenesulfonyloxy group, etc. Furthermore, when Xl or FiX 4 represents an alkanesulfonyloxy group, the alkanesulfonyloxy group is preferably a methanesulfonyl group, an ethanesulfonyl group, or an ethanesulfonyl group. It is a lower alkanesulfonyloxy group such as.

As described above, it is difficult to obtain p-prenylstyrene by reacting the compound represented by the general formula (P/) with a base. Bases include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, calcium oxide, sodium methoxide, sodium chloride, etc.
Rium et go sit.

Organic bases such as alkali metals such as potassium t-butyl, etc. can be used, and the amount used is according to the general formula CD
The amount is preferably about the same mole to about twice the mole of the compound represented by I). This reaction may be carried out in an inert solvent such as benzene, toluene, silane, hedPt, diethyl ether, diisopropyl ether, ethanol, methanol, etc. at temperatures ranging from about -30°C to about 120″cli degrees. Preferred. Also, by using a phase transfer catalyst, the reaction can be carried out in a two-phase system of an aqueous phase and an organic phase. According to this method (110K), p-prenyl It has the advantage of being able to obtain styrene.

For example, p-prenylstyrene, which is a compound of the present invention, can be produced as described above.

Reacts with carbon monoxide and hydrogen in the presence of a rhodium catalyst (
Hydrophorolation reaction) to form -a-(p-prenylphenyl)flopionaldehyde, which is then easily oxidized with silver oxide or other suitable oxidizing agent to form 2-CP-prenylphenyl). The acid that leads to propionic acid is produced.

Hereinafter, the present invention will be explained in more detail using examples.

Example 1 Turned magnesium 8.2 into a flask through nitric gas
ts Tetrahydrofuran 15- and 2 prime pieces (approximately 209) were added, and while stirring, 0.5-ethyl bromide was added.
When WLlt was added, the coloring caused by yamweed disappeared. Under stirring,
While heating and keeping at 110-120°C, a solution of 20f of p-prenylchlorobenzene in 11% tetrahydrofuranz was added dropwise.After the addition was completed, the mixture was further stirred at 120°C for 1 hour, and then cooled to a moderate temperature. Tetrahuman E27 Tun 7
Added 9.3 t of vinyl tetrahydrofuran 50WdbA to another 7:7 sco.

Ni((CsHs), P(CH*), P(C@Hs)
j) Ch O, 12f @insert.

At 10 to 20°C, Grignard solution prepared from the above p-grainyl tetrabenzene was added dropwise. After the dropwise addition was completed, the mixture was further stirred at the same temperature for 1 hour. Then, 13,011 liters of a 10% ammonium chloride aqueous solution was added to separate the organic layer and the aqueous layer, and the aqueous layer was extracted with 50% diethyl ether.
The diethyl ether layer was combined with the organic layer, washed with water, dried, and concentrated, and then 0.5' of 3,5-tert-butyl-4-hydroxytoluene (BHT) was added.
Jilt L? p −7' v nilx f y (
b, p, 68-70'C10,2mHf) l 2
．． 5 Get t. There are six constant magnetic resonance spectra for this substance as follows.

"HNMR (CDCIg): J 1.57-1.7
21 (m, 6H).

3.25 (d, J = 7Hz, 2H).

&O~5.4 (rn, 2H).

5.6 ('s J=18Hz t i ”) *6
．． 62(dd, 1IHz and 18I(!.

IM), 7.0 to 7.35 (mt 4H) ppm.

Example 2 Tetrahydrofuran 70+ in a flask through nitrogen gas
aj and Ni((C1Hs), P(C)h%
P(Csm), ) C150, 12ft-Insert this? The temperature was cooled to 30°C, and vinyl chloride was supplied through a glass tube into the tetrahydro 7 run liquid, and about 1% of the vinyl chloride was added.
5ft - collected ft.

p-prenylchlorobenzene 201 was added to this solution.

After the dropping was completed, the mixture was stirred at the same temperature for 1 hour, and then treated in the same manner as in Example 1. After distillation, 10.1 ft of p-brenyl styrene was obtained.
Obtained.

Example 3 Magnesium shavings 3.2 in flask through nitrogen gas
t, tetrahydrofuran 5011j and sulfur prime pieces (
About 20 cm) of ethyl bromide was added, and while stirring, 0.
When 5- was added, the coloring caused by sulfuric acid disappeared. While stirring, do not reflux the melt and add Cp-prenylbromobenzene 25.
．． A solution of 9 F in Na2-hydrofuran 3011 was added dropwise. After the addition was completed, the mixture was further stirred at the same temperature for 1 hour, and then cooled to room temperature.

Add 2 5 ml of tetrahydrofuric acid to another flask by passing nitrogen gas through it.
0 N1 ((CsHi), P(CHa), P(CaH
i), ) C1* 0. 1 2 f t-put.

The Grignard solution prepared from p-prenylbromobenzene above was added dropwise at 1O~20°C. After the addition was completed, the mixture was further stirred at the same temperature for 1 hour. Then, it was treated in the same manner as in Example 1 and after distillation. p-prenylstyrene 13. I got lf.

Examples 4-13 *N1 ((Csm), p(c turtle) in 11alFH
,, P (Ca picture), Cl2O, 11th instead of 12F
The Group I metal compound of the periodic table described in No. 1 is used in the amount described in No. 111, and mNx. ! ：Prepared from p-prenylchlorobenzene and magnesium in the same procedure 11, and reacted with a large Grignard reagent and vinyl bromide to produce p-prenylstyrene. The amount of a in p-prenylstyrene was as shown in Table 1.

Table 1 (Note) In the table, aeac represents an acetylacetonate group, Ph represents a phenyl group, and 1M represents a methyl group.

Example 14 Magnesium shavings 19F, Tetokuhydro 7Tsun 30s+j and Soda prime pieces (approximately 10
11If), and while stirring, add 0.0% of ethyl bromide.
After addition of 2-, the coloring caused by the other element disappeared. Then p-
Chlorstyrene 10.9f (Df trahydrofuran 20
The d@ solution was added dropwise at a rate that kept the reaction temperature at 45-55°C. After the dropwise addition was completed, the mixture was further stirred for 1 hour at the same temperature, then cooled to room temperature (approximately 20°C), and a solution of 8.2 g of prenyl chloride in 1 l of tetrahydrofuran was added to 20 to 25 g of a solution of 8.2 g of prenyl chloride in 1 liter of tetrahydrofuran.
The solution was added dropwise at ℃, and after the addition was completed, it was left at room temperature overnight. Add 80 wJ of a 10 weight ammonium chloride aqueous solution, separate the organic layer and the water layer, extract the aqueous layer with 40 d of diethyl ether, wash the diethyl ether layer with the above organic layer, wash with water, dry, concentrate, and distill. This gave 8.61 hp-prenylstyrene.

Example 15 A Grignard solution of p-bromustyrene was prepared in the same manner as in Example 14 using 14.4 F of p-bromous styrene and 1.9 F of magnesium. It was reacted with 8.2f of prenyl chloride and then treated in the same manner as in Example 14 to yield 8.9ftl of p-7'renylstyrene.

Example 16 1. Potassium hydrogen sulfate was added to a benzene 5011j solution of 1-(P-prenylphenyl)ethanol and 7f. Example 17 Caricum tert-butylene styrene was washed with a 010 sodium hydroxide aqueous solution that was refluxed for 2 hours, washed with water, dried, concentrated, and then vacuumed to obtain 2.5 f of p-prenylstyrene. 2.2POt-butanol 20
1-chloro-1-(p-prenylphenyl) i in m solution
- In the evening, 3.9 t of t-butanol 10 m solution was added dropwise at room temperature, refluxed for 1.6 hours, concentrated the reaction solution, added 50 m of n-hexane, washed with water, dried**, and distilled off the solvent. Then, it was distilled under reduced pressure to obtain 2.4f of p-prenylstyrene. l! Example 18 Toluene 30d and potassium hydroxide 8. Add Of and heat to dissolve, 1-riao-x-(p-prenylphenyl)ethane 4.8FO) toluene 101111! Drop the liquid, 6
After washing the O reaction solution that had been refluxed for a period of time and drying it, the S rope was distilled off.
Distilled under reduced pressure to obtain 72.8f of p-grenyl styrene.

Example 19 To a Grignard solution prepared in the same manner as in Example 1 from 20 t of p-prenylchlorobenzene and 3.2 f of p-type magnesium, 301 L of a solution of ethylene oxide & Of in tetrahydrofuran was added dropwise at room temperature. 0 drops completed. After 1
After heating under reflux for an hour, cool it down with a power source.

Add ammonium chloride aqueous solution and extract with diethyl ether. Wash with water, dry, and transfer to ll1Iiii41.
Purified by silica gel column chromatography to produce 2-
(P-7'renylphenyl)-1-ethyl f1
I got 34.

Adding 5f of potassium hydroxide to 5f of 92-CP-prenylphenyl)-1-ethanol obtained by the above method,
After heating to 200°C, it was distilled under reduced pressure. By redistilling the obtained distillate, 1.3% of p-fluorstyrene was obtained.
f 48 ta.

Example 20 &2-(P-prenylphenyl)-t-ethanol obtained by the method of Example 19 in 5.0 ft-7
114, add pyridine 106f and dissolve 9(1,-1
1.80 f of phosphorus trichloride was added dropwise at 0°C to 0°C. After the addition, the organic layer was stirred for 1 hour, concentrated, and separated by adding n-hexane and water.
5.2 p-7”renylphenyl)-1-chloroethane
5 F obtained 0 2-(p-prenylphenyl)-1-chloroethane obtained by the above method 4.8 t woll
) Dehydrochlorination was carried out in the same manner as in LM18, and 2.4 t of p-prenylstyrene was obtained.

Reference Example 1 Magnesium shavings were placed in a flask through which nitrogen gas was passed.
3F, tetrahydrofuran 800- and one prime piece (
About 0.1 t) of ethyl bromide was added, and while stirring, ethyl bromide
When 11J is added, the coloring caused by iodine disappears, and the preservation of contents and objects increases. Tetrahydrofuran t-jltlL
While stirring, a solution of p-dichlorobenzene (29+f) in tetrahydro7ran (21) was added dropwise over about 4 hours. After the addition was completed, the mixture was stirred for a further 2 hours and then cooled to room temperature. Then, a tetrahydrofuran (800 resistance) solution of prenyl chloride (271,7f) was added dropwise at 15 to 20°C over about 4 hours. After completion of the dropwise addition, the mixture was left at room temperature overnight.

Then, 24 ml of ammonium chloride aqueous solution was added,
Separate the organic layer and aqueous layer, and add 30% of the aqueous layer to diethyl ether.
The diethyl ether layer was combined with the previous organic layer, washed with water, dried, concentrated and distilled to extract p-prenylchlorobenzene (b, p, 64-6 & 5℃ 10.38-HP
)222.3f was obtained. The nuclear magnetic resonance spectrum selected for this turtle was as follows.

'H-NMR (CDCl5): J 1.66 (6
H,-d, J-4,5Hz), 3.23(2H,
d, J=7.4Hz), 5.21(IH,t,J=
7.5Hz).

6.94-7.26 (4H, In) plPm.

Magnesium 9.6 milled into a flask through nitrogen gas
f, 30 MI of tetrahydrofuran and a few pieces of sulfur prime (approximately 50 q) were added, and while stirring, ethyl bromide 2- was added, and the coloring caused by the polluting element disappeared. While stirring and maintaining the temperature at 110-120°C, 60 t of p-prenylchlorobenzene was added, and 2 t of tetrahydrofuran was added during the reaction.
After reacting for 4.5 hours, the mixture was cooled to room temperature, tetrahydro7ran 20011j was added, and a solution of acetaldehyde (22, Of) in tetrahydrofuran (30d) was added dropwise at 5 to 10°C over about 2 hours. After 0 drops, 1
Stir for 90 hours, then add 10% ammonium chloride aqueous solution (400ml) to separate the organic and aqueous layers, extract the aqueous layer with 30ml of diethyl ether, and combine the diethyl ether layer with the organic layer. 1-(p-prenylphenyl)ethanol (b,
p, los ~ 110°C, 10.5 ■ HP) 47.3f was obtained. The nine nuclear magnetic resonance spectra measured for this product were as follows.

H8MR (CDCIs): δ 1.36 (3H, d
, J=6Hz), 1.67 (6H, d, J=5Hz) 2.26 (IH, I) 3.25 (2H, d, J=7.4Hz) 4.73 (I
H* q+ J= 4.8) 1z ) 5.25 (I
H, t, J-7,6Hz) 7.0 to 7.3 (4H
1m) pPm.

Reference Example 2 Magnesium shavings 55% were placed in a flask through which nitrogen gas was passed.
IF, tetrahydrofuran 800d and several pieces of iodine (
about 0.1F), and while stirring, add ethyl bromide 2
When d was added, the coloration caused by iodine disappeared and the temperature of the inner spring material increased. Then, p-dipromobenzene (4462
) in tetrahydrofuran (2J) at a reaction temperature of approx.
It was added dropwise at a rate that maintained the temperature between 5 and 30°C. After the dropwise addition was completed, the mixture was further stirred for 1 hour and then cooled to room temperature. Then, a solution of prenyl chloride (256,8F) in tetrahydrofuran (800 wLl) was added dropwise at 15 to 20°C.

After completion of the dropwise addition, the apparatus was kept at room temperature (approximately 20° C.) overnight.

Add 2j of lO weight aqueous ammonium chloride solution, separate into an organic layer and an aqueous layer, and add 3001 L of diethyl ether to the aqueous layer.
Extract with #, wash the diethyl ether with the previous organic layer, wash with water, dry, concentrate * # Distill to give p-prenylbromobenzene (b, p, 7o~83℃ 70.3swm HP) 27
I got 0F. The magnetic resonance spectrum measured for this product was as follows.

"HNMR (CDCIm): δ1.70 (6)1.
d, J-5Hs) 3.22 (2H, d, J-BH
z) 5.22 (IH, t, J=7.6Hz) 6.98
(2H, d, J=9Hz) Bow -- 7,33 (2H, d, J=7I(x) Ppm.

Reference Example 3 RhH(CO) [P(CsHs) 8:]80.
Dissolve 25 mmol of triphenylphosphine and 5.0 mmol of triphenylphosphine and charge 200 HLl of a nine-benzene solution, fill the autoclave with nitrogen gas, then fully replace it with a mixed gas of hydrogen and carbon monoxide in equimolar proportions. The autoclave was maintained at 40 atm (absolute pressure) K with a molar mixed gas and heated until the internal temperature of the autoclave reached 80°C. Thereafter, p-prenylstyrene 745F (0262 mol) was introduced over 1 hour using a quantitative bomb 1 while stirring vigorously.

Note that the autoclave is connected to the external 7
Connect to a gas stopper (filled with gas of the same composition as the autoclave) to replenish the gas consumed by the reaction.

During the reaction, the pressure inside the autoclave was maintained at a constant level. After the general discussion of p-prenylstyrene was completed, stirring was continued for an additional hour. After a total reaction period of 2 hours, the autoclave was allowed to cool and the pressure was released, and the reaction mixture was analyzed by gas chromatography. It was found that the remaining amount of unreacted p-prenylstyrene was 0.0052 mol, and the conversion of p-prenylstyrene was 61 (conversion of p-prenylstyrene). The yield of α-(P-prenylphenyl)propionaldehyde was 0.226 mol (selectivity 488%). In addition, 0.0257 mol of β-(p-prenylphenyl)propionaldehyde was produced (selection 410).

After removing benzene from the above reaction mixture, simple distillation was performed under reduced pressure to obtain a mixture of α-(p-prenylphenyl)propionaldehyde and β-(P-7'renylphenyl)propionaldehyde, which was further divided into nanometers. By distillation, α-(p-prenylphenyl)propionaldehy Y42. I got Of. The IH-NMR spectrum of the nine CDCIm solutions measured for this product was as follows. (I with hequinamethyldisiloxane as standard)
value) I & group α-(p-prenylphenyl) fropionaldehyde obtained by K as above 2. Of ethanol 400-
A 3.70 fO solution of silver nitrate in water was added to the solution, and while stirring at room temperature, a 0.5 N -NaOH aqueous solution 881
1E/ was slowly added dropwise over 2 hours, and stirring was continued for about 10 hours. After filtering the generated black precipitate, liquid F was concentrated and extracted with isopropyl ether, and the aqueous layer was acidified with hydrochloric acid to precipitate an oily substance. This was extracted with iso-10vinyl ether, washed with water, and the isopropyl ether was removed.
- Grail Fueni Af/) propionic acid was obtained. The NMR spectrum of this product completely matched that of a separately synthesized standard product.

Patent applicant Taisho jI11! Yakuhin Co., Ltd. Rira Co., Ltd. Representative Patent Attorney Ura Honda Continued from page 10 Inventor Manzo Shiono Kurashiki model Showa 2-2-2-340 Author Fujita Yoshiji Kurashiki model Showa 2-2-30 No. 0 Inventor Masuhiko Tamura 16, 961 Hirata Kurashiki Type Applicant Kuraray Co., Ltd. 1621 Sakazu, Kurashiki City Procedure Amendment-M (Voluntary) January 27, 1980 Haruki Shimada, Commissioner of the Patent Office 1, of the case Indication 1982 Patent Application @ 200661 2, Name of the invention p-prenylstyrene and its manufacturing method (2g1) Taisho Pharmaceutical Co., Ltd. ~ 11th position: Shoji Uehara (and 1 other person) 4, Representative: Kanji Hitokura Eyama 2045 No. 1 (] [llp I1g &) Kuraray Co., Ltd. Patent Department No. 1 East ME 03 (277) 31826, Contents of amendment (1) r 6H, d, J in line 17 of No. 24 of the specification
-4,5H 凰” is changed to IIH,l.

(2) Specification Prefecture 24j [Line 18 “J-7,4HzJ
is changed to rJ-7,5HzJ.

(3) [J-6HzJ on the bottom line of page 25 of the specification]
6,5ni”.

(4) raH, ti,, y-5 on page 26, line 1 of the specification
Change HzJ to "6H9l".

(6) 1-J-7, 4H on page 26, line 3 of the specification!
J is changed to "J-7,5HIJ.

(・) [J-t8HzJ on page 26, line 4 of the specification]
-6.5HJ.

(7n Specification Prefecture 26j [5th line (D f J-7, 6
Hz J is changed to [J-7,5HIK.

(8) rl, 7G (6H, d,
, L-5H+c)J is changed to ``1.66(6H,I)J.

(9) On page 27, line 10 of the specification, “J-9HKJ is changed to [J-7,5HIK.

1-J-7, 6H1 on the 27th purchase line 11 of the specification
Changed to J-7,5HKj.

CLI) 明11A'liM 27781.12 Line (1) l-J-9k (z J to "J-8,0) [1"
Changed to

(2) Specification Prefecture 273 [Line 13 (J-7H milk)]
0 changed to J-8,0ttZJ

Claims (1)

[Claims] (1) p-prenylstyrene. (2) General formula % formula % (in the formula, zl represents a prenyl group t or a vinyl group, and X
I represents a rogen atom ◇) Must be a Grignard reagent obtained from the compound shown by ◇) and metallic magnesium! According to the periodic table Group ■ metal compound catalyst #l is present, and the general formula % formula % (wherein zl represents a vinyl group when the above z1 is a prenyl group, and when the above z1 is a vinyl group In this case, it represents a prenyl group and XI Fi represents a halogen atom. One of which represents a hydroxyl group and the other represents a hydrogen atom.
- A method for producing prenylstyrene. (4) A base is added to a compound represented by the general formula (wherein, one of Xs and X4 represents a rogen atom, an arylsulfonyloxy group or an alkylsulfonyloxy group, and the other represents a hydrogen atom). A method for producing p-prenylstyrene by treating it with t* mold.