JPS6147450A - O-allylphenyl ester derivative - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (X is halogen; R is lower alkyl; R' is H or RCO). EXAMPLE:3-Acetoxy-2-allyl-4,6-dichloroacetanilide. USE:A synthetic intermediate for 4-hydroxyindole useful as a synthetic raw material for medicines, dyes and agricultural chemicals. PREPARATION:A compound expressed by formula II is acylated, and reacted with a halogen to give a novel compound expressed by formula III (R is other than Me), which is then reacted with an allyl halide to afford a novel compound expressed by formula IV. The resultant compound expressed by formula IV and a novel compound expressed by formula V are heated in the presence of an acylating agent, e.g. acetic anhydride, in a solvent, e.g. N,N-dethylaniline, at >=170 deg.C to give the aimed compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to an 0-allylphenyl ester derivative which is a precursor of 4-hydroxyindole and is useful as a raw material for the synthesis of pharmaceuticals, dyes and agricultural chemicals.

(Prior art) Tit, 4-1r, 1-d[L/T, etc., for the production of 2-allyl-3-aminophenol derivatives necessary for the synthesis of diindoles, etc. ,Δ
m.

Chem, 3 oc, vol. 64, p. 1023 (19
42)) According to (VII) (■) (X) Formula (13) However, only a small amount of compound (■) is obtained in this reaction,
Furthermore, fraction #1 from compound (IX) is also difficult. Therefore, the synthesis method for supported 4-hydroxyindole is based on
A method of converting 2,-diton-6-hydroxytol J-one obtained through several steps from
ahe(iron l, etl:,, vol. 24.

4561 pages (1983), also published by TA JP-A No. 7-99
No. 568), or a method using very expensive m-21-0 furanol as the starting material (JP-A No. 56-115'
771), a method using cyclohexyl-1,3-dione and expensive bromopyruvate (Ber,
, Vol. 101, p. 2605 (1968) or Japanese Unexamined Patent Application Publication No. 1997-1997).

As mentioned above, these methods have many problems as an industrial manufacturing method.

(Object of the Invention) The present invention does not have the drawbacks mentioned above, can be produced industrially advantageously, and is a precursor of 4-hydroxyindole.
The object of the present invention is to provide allyl phenyl ester derivatives.

(Structure of the Invention) Basically, the method shown in the above formula 1) is the most excellent for the synthesis of 2-allyl-3-aminophenol derivatives. Therefore, the present inventors developed a new formula that does not include the problem of regioselectivity in formula (B). -A! J)t7
:cyu), □neej)IyN conductor synthesis 6. The present invention was completed by determining that this product is a useful precursor of 4-hydroxyindole.

Specifically, the present invention is directed to O- represented by the following general formula (A>)
There are 9 arylphinyl T sprue derivatives.

COR I R' (wherein X represents a halogen atom, R represents a lower alkyl group, and R' represents a hydrogen atom or RCO.

The compound of the present invention (denoted as AI, A2) can be expressed by the following formula (
It is manufactured as shown in C).

(I), (I),,,
(II) (A2) (Vl)
Formula (C) In formula (C), the halogen atoms represented by x and x' may be the same or different, and chlorine and bromine atoms are preferred. R is a lower alkyl group having 1 to 5 carbon atoms (e.g., methyl, ethyl.

n-pentyl group, etc.). Furthermore, in the above formula (C), (IN
) (other than R=Me), (V), and (Vl) are new compounds.

Note that some acyl group exchange occurs during the acylation process, so
It is difficult to synthesize compounds in which the acyl groups in (A1.) and (A2) are different from each other.

These reaction steps will be explained in detail below.

A step of producing compound (I) by acylating compound (I).

This reaction involves compound (I) (m-aminophenol), carboxylic acids (e.g. formic acid, acetic acid, butyric acid, caproic acid),
This is carried out by the action of acid anhydrides (eg, acetic anhydride, propionic anhydride) or acid halides (eg, acetyl chloride, acetyl bromide, Yropionyl chloride). The ratio of acid anhydrides or acid halides to compound (I) is not particularly limited, but usually 1 to 1.5 moles of these reagents are used per 1 mole of compound (I), preferably 1 to 1.1 moles.
Use moles. Furthermore, when using acid halide, it is preferable to coexist a base in the reaction system in order to capture the generated hydrogen halide. Examples of such bases include pyridine, sodium hydrogen carbonate, sodium carbonate, and carbonate. Examples include potassium, sodium acetate, etc., and are usually used in an amount of 1 mol or more per 1 mol of compound (■).

The solvent for this reaction is water, alcohols (e.g. methanol, ethanol, isopropanol), carboxylic acids (e.g. formic acid, acetic acid, butyric acid), esters (e.g. ethyl formate, ethyl acetate), hydrocarbons (e.g. For example, benzene, toluene, heptane), halogenated hydrocarbons (for example, chloroform, carbon tetrachloride), pyridine, etc. may be selected from a wide range, but methods using carboxylic acids as reagents and solvents, or hydrocarbons or halogenated A method using acid anhydrides in a hydrocarbon solvent is most preferred.The reaction temperature is not particularly limited, but is usually carried out at 0 to 150°C or around the boiling point of the solvent, and is completed at about 0.5 to ZWi. .

○ One culm in which compound (■) is produced by reacting halogen with compound (I).

As the halogen used in this reaction, chlorine and small atoms are preferred. Compound (I) and iodine do not react under normal conditions and require a special tk reagent such as -iodine chloride, which is economically undesirable.

The ratio of compound (i) and halogen used is usually 2 to 2.5 mol, preferably 2 to 2.1 mol of the latter per 1 mol of the former. Solvents for this reaction include water, alcohols (e.g. methanol, ethanol, isopropanol), carboxylic acids (e.g.!!! acid, acetic acid, butyric acid), halogenated hydrocarbons (e.g. chloroform, carbon tetrachloride), You can choose from a wide range of options, such as dimethylborumamide, but
Particularly preferred are carboxylic acids and halogenated hydrocarbons. In addition, when producing compound (■), carboxylic acid is used as a solvent and I
When used in J, it is most convenient to halogenate compound (I) from compound (,T) using the same reaction setup without isolation. Depending on the reaction conditions, it may be necessary to neutralize the hydrogen halide produced.

One such neutralizing agent is sodium hydroxide.

Examples include potassium carbonate, sodium acetate, and sodium phosphate.

The reaction temperature of this reaction is not particularly limited, but it is usually carried out at 60°C or higher in the case of chlorine and 20 to 60°C in the case of bromine. The reaction proceeds quickly, and when carboxylic acids are used,
The treatment is completed within 0.5 to 1 hour after the appropriate introduction of 1 gen. Furthermore, when halogenated hydrocarbons are used, it is preferable to complete the reaction by refluxing.

A step of producing compound (V) by reacting compound (IV) with O compound (Iff).

The allyl halide represented by the general formula (]V) is preferably allyl chloride or allyl bromide. The solvent used in this reaction and the base coexisting can be appropriately selected within a wide range. Such solvents include water, alcohols (eg methanol).

ethanol, isopropanol, butanol), amides (e.g. dimethylformamide, dimethylacetamide, N-methyl-2-piperidone), ketones (e.g. acetone, methyl J, tilketone) and mixed solvents thereof; Sodium hydroxide, potassium hydroxide.

Examples include calcium hydroxide, anhydrous potassium carbonate, anhydrous sodium carbonate, pyridine, and triethylamine. Compound (■) in this reaction.

The ratio of compound (IV) and base used is not particularly limited, but usually compound (IJ7) is used in a ratio of 1 to 1.5 mol, preferably 1 to 1.2 mol, per 1 mol of compound (■).
It is preferable to use the base in a proportion of 1 mol or more, preferably 1.5 to 2 mol. This reaction is usually carried out near the boiling point of the solvent or at 10
It is carried out at around 0° C. and generally takes about 3 to 5 hours to complete.

O Compound (V) and Compound (Vl) were heated in the presence of an acylating agent for 1 min to form Compound (A1) and Compound (A2), respectively.
The process of manufacturing.

Acylating agents used in this reaction include acid halobides (e.g. acetyl chloride, acetyl bromide, propionyl chloride), acid anhydrides (e.g. acetic anhydride, 70-pionic anhydride), I prefer the latter. Compound(
The ratio of the acylating agent to V) and (Vl) is not particularly limited, but the ratio of the acylating agent to 1 mol of compounds (V) and (■) is usually 1 to 5 mol, preferably 1.2 to 2 mol. used in As the solvent for this reaction, N,N-dimethylaniline and N,N-diethylaniline are most suitable, and if the solvent is used or no solvent is used, the yield will be extremely reduced. Furthermore, even when dialkylaniline is used, the yield will decrease if an acylating agent is not present. Lower acid anhydrides (eg, acetic anhydride) can also be used as reagents and solvents.

In this case, the reaction rate of ms water with a boiling point of 170°C or lower is slow and is not practical, but with acid anhydrides (e.g. caproic anhydride) with a boiling point of 170°C or higher, the compound (A2 ) is obtained. This reaction is usually carried out under a stream of inert gas such as nitrogen gas or argon gas near the boiling point of the solvent, and is generally completed in 6 to 11 hours.

Compound (V) and compound (AI) are heated in the presence of an acylating agent to form compound (Vl) and compound (A2), respectively.
T culm that produces.

Acylating agents used in this reaction include acid halogenides (e.g. acetyl chloride, acedel bromide, propionyl chloride) and acid anhydrides (e.g. acetic anhydride, butyric anhydride).
The latter is preferred. Compound (V) and (
The usage ratio of AI) and acylating agent is not particularly limited, but
Usually, the amount of the acylating agent is 1 to 10 mol, preferably 1.5 to 5 mol, per 1 mol of compounds (V) and (■). As mentioned above, this reaction is necessary when using i1 anhydrides with a boiling point of 170"C or lower, and if an acid anhydride with a boiling point of 170"C or higher is used, simply heating it to 170"C or higher will complete the reaction at once. Compound (A2) is produced from compound (V).Solvents for this reaction include ethers (such as "dio": san, diglyme), esters (such as Pudyl acetate, Pudyl).
ethyl pionate), hydrocarbons (e.g. toluene, xylene, heptane), halogenated hydrocarbons (e.g. I~
dichloroethane, tetrachloroedylene), dialkyl niline (e.g. N.

The acylating agent may be appropriately selected from inert solvents such as N-dimethylaniline, or the acylating agent itself may be used as the solvent. This reaction is usually carried out at a temperature of 100 DEG C. to around the boiling point of Ura-san using a carboxylic acid salt (for example, sodium salt, potassium salt) as a catalyst, but when dialkylaniline is used, it is preferable not to add salts. Generally, the urine reaction is completed in about 3 to 6 hours, but if no carvone* salts are added, a longer period of time is required.

Examples will be described below along with reference examples. In addition, all composition percentages in the examples are based on weight.

Reference Example 1 Synthesis of 3-acetylamino-4;6-dichlorophenol (compound Tl: X=CI, R=Me>.

280 m# of glacial acetic acid was added to 20 q of m-aminophenol, and the mixture was heated under reflux for 5 hours. Chlorine 1 was then liquefied outside the system.
81e was introduced into the reaction system at 60 to 70°C together with nitrogen □ gas. Yellow needle crystals precipitated near the end of ti L6 It'. The solvent was distilled off under reduced pressure, water was added to the residue, and 1
It was set to 1. After suction filtration of the crystals, washing with water, and drying, 3-
Acedylaminoni 4,6-dichloro[1phenol 34.
Got a 4*. Yield is 89.1%. This product was recrystallized from chloroborum, and the results were shown in figs 234.8 to 236.
It gave colorless acicular crystals at 6°C (literature value 233-236°C).
).

T R (N'ujol) cv-': 1682.1
608.15'47°1468,138O NMR (Atton-ds) δ: 2,06 (3) 1
, s), 7.37 (IH,S).

8.02 (Ill, S), 8,65 (1.br, s per month), 9.3m (11-1, br, s) Reference example 2 Synthesis of 3-acedelamino-4,6-dibromophenol (compound 11 [: X=Br, R=Me).

, l11-amino"7Jnor20!I I: Glacial acetic acid 2
00■p was added and the mixture was heated under reflux for 5 hours. The reaction solution was heated to 20°C.
The mixture was cooled to 200 ml, and 2nd bromine was added dropwise. The reaction temperature was raised to around 60° C. and stirred for an additional 30 minutes after the dropwise addition was completed. The solvent was distilled off under reduced pressure and the residue was poured into 500 IIll of water. After suction-filtering the crystals and washing them with water three times, they were dried and prepared as 3-i.
′! Thylamino-4,6-dipromophenol 54.6
9 was obtained (yield 96.4%). When this material is recrystallized from 10 form, the melting point is 242.3-242.9℃.
A colorless microscopic single crystal was obtained (literature value: 245°C).
.

11R(NlljOl) cm': 1675.1
600.1590°54O NMR (DMSO-ds) δ: 2.08 (
3H,s>, 7.44 (1t-I,S)
.

7.70 (ll-1,s), 9.2
3 (IH, br, s), 9.64 (IH, br, s) Reference Example 3 5.09 m-aminophenol was suspended in 45 C of carbon tetrachloride, and 4.4 C of acetic anhydride was added at once. In addition, 2 pieces
Stirred for 0 minutes 1/tc 0 After adding 19.5 parts of disodium phosphate anhydride A to the reaction solution, 5.011 parts of bromine was added dropwise. The temperature of the reaction solution was 40 to 60°C, and the reaction gradually slowed down. Dripping completed 4r21 hours) 7 times. After cooling with N1, the reaction solution was filtered, thoroughly washed with carbon tetrachloride, washed with 20 (1++5) water, and dried to obtain 12.8'j of 3-alinodylamino-4,6-dibromophenol.The yield was as follows: 90%. This product was compared with the specimen obtained in Reference Example 2 and identified.

Reference Example 4 Synthesis of 4.6-dibromo-3-caproylaminophenol (compound m: X=I3r, R=n -Cs
l・l++).

m ~ Amitsuno ■ Nor 20.09, Anhydrous Capron M4
2.6m/ 1t',)-Tchi)Ly7'min2.
(hO t-)Lt was suspended in 200 mff of hydrogen, heated under reflux for 1 hour to remove the IC6 solvent, and the residue was acetic acid]
- 10% hydrochloric acid dissolved in chill.

It was washed with saturated chlorine water and saturated brine and dried. The remaining 2.5t obtained by distilling off the solvent was dissolved in 1j) 1ρ of glacial acetic acid, and 1 bromine, 8. (When λ was added, the reaction solution became nR red, and after a while, green crystals were precipitated.)

The solvent was distilled off under reduced pressure, 300 ml of water was added to the residue, and the crystals were filtered. The crystals were washed with water, then thoroughly washed with benzene-to-sodan (1:2) and dried to obtain 4,6-dibromo-3.
-Caproylaminophenol 51,891! ? is(
yield 11.3%). When this product was recrystallized from isopropyl ether, it gave colorless nail-shaped crystals with a melting point of 201.2-202.5°C.

IR(NUjOI) cm-': 1670.16
02.1550°NMR (CDCI 3-CD30D)
δ20.70 ~ 2. M (11H,ra
>.

3.75 (2H, br, s).

7.62 (month-1,s), 7.93 (
'11-1. S) Elemental analysis (as Cut-13Br2NO2) CHN
Br Raccoon theory value (%) 39.48 4.14 3,84 4
3.78 Actual value (%) 39.70 /1.04
3.95 43.59 Reference example 5 (3-aceplamino-4,6-dichloro[1 phenyl)
Synthesis of allylneedle (compound V: X-C1, R=Me
).

3-acetylaminol 4.6-dichlorophenol 20
．． 09, allyl bromide 9.2@/! % anhydrous potassium chloride (26.09%) was suspended in 200 me of methyl ethyl ketone and heated under reflux for 4 hours. The solvent was distilled off under reduced pressure, and 200 μg of water was added to the residue. The crystals were filtered with suction, washed once with water and dried once in direct contact with each other, to give (3-aceplumino-4,6-dichronic lophenyl) allyl ether 23,49 at 18k (yield 9).
8.3%). When this product was recrystallized from a filter, colorless monomorphic crystals with a melting point of 123 and 6 to 125.4°C were obtained.

(R(N11.toI)cm”: 167
2, 1! i98, 1530.

1462, 14(1(I NMR (CI) Cl 3 ) δ: 2.22 (
3H, s), 4.62 (2H,
d, J.

! i,4t-1z), 5.15-6.56(
31-l, m), 7.33 (1N
.

s), 7.61 (IH, br,
s).

8.18' (IH,s) Elemental analysis (as Col-111CI2N02) HNCI value (%) 50.79 4.2B 5,38
27.26 Actual value (%) 50.82 4.32 5
．． 46 27.36 Reference Example 6.

Synthesis of (3-acetylamino-4,6-dibromophenyl)allyl ether (compound V: X=Br, R=Me
).

3-acetylamino-4,6-dipromophenol 54
．． 69, allyl bromide 17.2 p, anhydrous potassium carbonate 409 were suspended in 200 m12 of methyl ethyl ketone.
The solvent was distilled off under reduced pressure, and the residue was extracted with hot methylene chloride-methanol.
When the solvent was distilled off under reduced pressure, (3-acetylamino-4,6-dibromo7 and enyl)al
61.99 m of NorT-thyl was obtained (yield 96.7
%). When this product was recrystallized from benzene with ↑san, colorless nail-shaped crystals with a melting point of 151.0 to 153.0°C were obtained.

IR(NIJjoI) cm-”: 1655.15
70.1455°NMR (CI)Cl 3) δ:
2.23 (31-1,s), /1.58
(2H, d, J=5.41-12), 5.
14-6.20 (31-1, If), 7.55
(IH.

br,s), 7.66 (IH,s),
8.18 (Month 4.S) Elemental analysis ((as Cu Hu Br 2 N O2)
CI-IN Br Theoretical value (%) 37,85 3.18'4.01'
45.79 Actual value (%) 37.57 3.37
4.10 4! +, 50 Reference Example 7 Using the same method as Reference Examples 5 and 6, (4,6-dibu[]]mo 3-caproylaminophenyl del (Compound V: X"=FSr, R=n Strawberry c51"++) was synthesized.Number band 9o%, melting point: 92.
7-94, 6℃ (colorless fine IRtI-like crystals from hexadiene)
Elemental analysis (CI4) - 1yy 13r 2 as NO2) C H N Br theoretical value (%
) 42.99'4.38'3.58 40.86
Actual value (%) 43,16 4,52 3.36
40.68 Example 1 Synthesis of 3-acetoxy-2-allyl-4,6-dichloroacetanilide (compound Al:X=CI.

R=Me).

(3-acetylamino-4,6-dichlorophenyl)allyl ether 23.49 N. N-dimethylaniline 1
00. After adding 17.7 ml of acetic anhydride, the mixture was heated and centrifuged under a nitrogen stream for 11 hours. The solvent was distilled off under reduced pressure, and the residue was dissolved in 200 ml of ethyl acetate. This solution was diluted with 10% hydrochloric acid and saturated with water.

It was washed successively with saturated saline and dried. The solution was filtered and the solvent was distilled off to obtain 33.3 cJ of a crude product of 3-acetoxy-2-allyl-4,6-dic00acetanilide.

This product 11 was taken and purified by silica gel and chloroform-methanol chromatography to obtain 677 wq of pure 3-acetoxy 2-allyl-4,6-cycloacetoanilide (yield 83%). This thing beam 1
] When recrystallized from a chill, colorless needle crystals with a melting point of 174.2 to 175.0'C are obtained.

'IR' (NIIjOI) ell ""
: 1770, 1672. 1! '+16.

46O NMR (C'D'CI3)δ: 2.26
(31-1, S)', 2.34 < 3H
．． S'＞.

3, 20-3.54 (21-1, 11).

'4.80~6.08 (31-1, If
).

7, 44 (11-1, br.s).

7, 55 (If-1, s) Elemental analysis (
CI3 I-1+3(] 2 NO3tLt')HNC
I fill value (%) 51.68 4.34 4.64
23.47 Actual value (%) 51.55 4.2
7 4,63 23.26 Example 2
゛” child-acetoxy 2-allyl-4.
6-”Synthesis of pro-acetanilide (compound A':
X=Br.

R=Me　　　　　.

As in Example 1, (3-7zetylamino-4,6-dibromophenyl)allyl ether 61.99 t1',l
t Water AT Ml 33. ! When nff is reacted in N,N-dimethylaniline 300*0 and post-treated, 3
70.99 of a crude product of 2-allyl-4,6-dibromoacetanilide was obtained. 1cJ later
was purified with silica gel and chloroform-methanol to obtain pure 3-Al'! 1-xy2-allyl-
4,6-dipromoa tr+~anilide 831 town was obtained.

(Yield 82%). When this substance is recrystallized from mebru ethyl ketone-isobrobyl ether, it has a melting point of 193.2~
Colorless 11-shaped crystals were obtained at 171.8°C.

I R (NIIjOl) cm-': 1763,
1664. 1! i13.

46O NMR (are]-ds) δ: 2,13 (
3+-1.

s), 2.35 (31-l, 3).

3,08~3.44' (2+-1, Ill)
.

/1.80-, 6.05 (3H
, III).

7, 87 (nl. s > elemental analysis (Cp3Ha3B r 2 N 02 and C
)(': 11 'N Br Sokuronsen (%) 39.93 3.3!i 3,!i8
/10.87 Actual value (%) 39,93 3.
2! i 3.60' 40.73 Example 3 5-nor7lyl A1 C 2,4-dibromoaniline N,
N-sia j? Synthesis of zalimide (compound ■: X=.Rr
,Igu==Me),.

(3-horn side-1 delamino-4.6-jib [IL
) J-nyl) allyl-[-thyl 1,08 9 and 0.1 tb of sodium acetate trihydrate in acetic anhydride. 'im/suspended (
] The mixture was heated under reflux for 4 hours. The solvent was distilled off under reduced pressure, 1 to 1 toluene was added, W1 was removed again under reduced pressure, benzene was added to the residue, the inorganic salt was filtered off with suction, and the filtrate was distilled off under reduced pressure to obtain the crude product 1. 46 g was obtained. This is silica gel, black [1
Purification by form-methanol column chromatography yielded 1,129 5-allyloxy-2,4-dizo1](aniline N.N-diacetylimide (yield 92.6%).

-23~ When this product was recrystallized from carbon tetrachloride-hexane, colorless needle crystals with a melting point of 98.0 to 101.5°C were obtained.

T R (Nll, iol) cm-': 1727
, 1709, 1590.

14/15, 137O NMR (CDCI3,) δ: 2.29 (
61-1. s), 4.59 (2)
-1, d, J=4, 2Hz), 5.0
8-6.32 (3H, m), 6.76
(IH.

s>, 7.86 (iH. S) Elemental analysis (as C10 1-1+3 Br 2 N O3) (, t-l' N Br immediate value %) 39.93 3,35 3,! '18
40.87 Actual value (%) 40.03 3, 52
3,6! i 40.67 Example 4 5-allyloxy-2,4-dichloroaniline N was prepared in the same manner as in Example 3. N-Diacetylimide (compound Vl
: X=CI, R=Me) was obtained.

Yield: 89% Melting point: 83.3-84.1°C (colorless needle crystals from hexane)
Toshi”rJ )0 11 N CI Theory 4Pi (%) !i1.68 4,34
4,64 7:(, 47 actual value (%)!i1.83
4,30 4. ! is 23,641 Example jj 3-7' tbi1-xy2-)noryl-4,6-dipI] Synthesis of moaniline N,N-diacebulimide (compound Δ2: X·-11r.R=fvle).

Obtained f. in Example 2. ．． :3. -acetoxy- 2~
70.9 q of crude/1 product of allyl-4,6-dipromo l=1 to anilide was dissolved in 200 ml of acetic anhydride ((), 5 ml of putrium acetate trihydrate was added, and the mixture was heated under reflux for 4 hours. The solvent was distilled off under reduced pressure, 30 d of toluton was added to the residue, and evaporated again under reduced Ff. 150 d of benzene was added to the residue, inorganic salts were removed by suction filtration, and the filtrate was concentrated under reduced pressure. 3-Al= l-xy-2-allyl-
A crude product 72.Og of 4,6-dipromoaniline N,N-diacenalimide was obtained. Take this one 1.01,
The product was purified using silicage J and chloro[]]form-methanol to obtain 690 pieces of pure imide (yield 64% in total from allyl gothyl (V)).

When this substance is recrystallized from methanol, its melting point is 87.0.
Colorless plate-like crystals were obtained at ~88.8°C.

T R (N11jol) c+n-': 1780.
1732.1712°1454,1376 NMI (CDCI3) δ: 2.27 (61-
l, s), 2.35 (3+-1, S)
.

3, (1! to i, 3.50. (21-1, l
).

4, /19 ~ 6.03 (3H, m)
.

7.88 (11-1,3) Elemental analysis (as Cs Has Br 2 NO4) C
11N Br Theoretical value (%) 39,93 3,35 3,58 4
0.87 actual measurement (%) 40.03 3.52 3.
65 40.67 Example 6 Synthesis of 3-allele-1cy-2-allyl-4,6-dipromoaniline N,N-diacetylimide (chemical
Compound A.: X=11r, R=M.).

According to Example 3 (3-acetylamino-4,6-di1
11]-phenyl)allyl-1-thyl 2.09 to 1q
5-Aryl O↑Sea 2,4-Jib ■-[, Arlin N
, N-thia 1f purimide crude product 2.479,
N-dimethylaniline 12.5w4! Dissolved in, add anhydrous acid resistant 1,2 + iff and heat under nitrogen stream for 6 hours]!
It flowed. The solvent was evaporated under reduced pressure, the residue was dissolved in acetic acid, and this solution was washed successively with 10% hydrochloric acid, saturated HCl, and saturated brine, and dried. Distill the solvent under reduced pressure 1 and 3
-Acetoxy-2-allyl-4,6-dipromoaniline N,N-Sial=Delimide Phase 1 product 2.71 was obtained. This product was purified by column chromatography using silica gel and chloroform-methanol to obtain 2.49 pure imide compounds (total yield 96.5% from the allyl ether compound). This product was compared with that obtained in Example 4 and identified.

Example 7 3-acetoxy-2-allyl-4,6-dichloroaniline N,N-diacetylimide (compound A2: X=CI) was prepared in the same manner as in Example 5.6.

R=MO) is the synthesis number 1. The yield is calculated from the allyl ether form, and is 64% for the route via compound A1, and the yield is 64% for the route via compound A1.
The rate was 77% for those who took the route.

Pale yellow oily substance.

IR (liquid film) cm-': 1778.1715.1
468.1460°NMR (CDCI3) δ:
2.28 (6H,S), 2.36, (31
-1,s).

3.07~3.43 (,2H,Ill)
.

4.81-6.14' (31-1, m).

7.57 < 11-1.3) to resolution MS theoretical value 301.9999, 303.9932 (M
+ -Ca Hs ) Actual value 301,9987, 303.9957 Example 8 Synthesis of 3-alethoxy 2-allyl 4,6-dipromoaniline N,N-diacetylimide (compound Δ2:
X=Br, R=Me”).

(3-acetylamino-4,6-dibromophenyl) allyl ether 10.09 and anhydrous vinegar 94.05 ■C N,
The solution was dissolved in 50μ of N-dimethylaniline and refluxed for 8 hours under a nitrogen gas stream. Furthermore, 13.5 ml+ of acetic anhydride was added, and the mixture was refluxed again for 8 hours under a nitrogen gas stream. The solvent was distilled off under reduced pressure, the residue was dissolved in 50 m# of ethyl acetate, washed with 10% hydrochloric acid and saturated brine, dried, filtered, and the solvent was distilled off. Arifurei 4.6-dibromoaniline N.

13.49 of a crude product of N-diacetylimide was obtained.

Analysis by high performance liquid chromatography (Silica-01) S
Using a column, elute with methanol-water (7:3))
As a result, the purity was 87.6%, so the pure product yield was 94. It was Ei%.

Example 9 Synthesis of 2-allyl-3-caproyl-1-4,6-dipromoaniline N,N-cicabroylimide (compound △2: X = li r , R = n C6H1
1) (4,6-dipromo-3-caproylaminophenyl)
Allyl ether 5.0g and anhydrous vinegar wIf thorium 0.5
1 was suspended in 25 g of anhydrous Capron M and heated in a 180° C. oil bath for 4 hours. Caproic anhydride was distilled off under reduced pressure, toluene was added to the residue, inorganic salts were filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 10-form-methanol column chromatography to obtain 2-allyl-
7.8 g of 3-caproyloxy-4,6-dipromoaniline N,N-cicabroyl imide (yield: 91
%). Yellow oily substance.

IR (liquid film) cm-': 2962, 2936,
1774, 1723.

NMR (CDCI3)δ: O,! i3~2.
82 (33H, m), 3.02-3, 33
(2H, rn),
4.80~5.99 (3+-1, m
>.

7, 86 (Month 1, s).

High resolution MS theoretical value 460.0115, 462.0095 (
M10-09 1415 0) Actual measurement value 460,0132, 462.0071 (
Effects of the Invention) Tree Invention (〇 -allylphenyl ester 'ER 7M compound represented by the general formula (Δ) by J is oxidized and reductively treated with ozone etc. in an organic solvent to obtain a phenolic acetaldehyde derivative. be able to.

COR COR(Δ) This reaction proceeds in good yield and uses a mild 7-element reagent for the reductive decomposition of the produced A cinide.

This phenylacetaldehyde derivative can be subjected to a hydrolysis reaction accompanied by a deacylation reaction to produce 4-human[1-xindole.

OCOR Ol-1X
Palladium and rhodium are used as I + -IOR 4- and droxiindole hydrolysis reagents.

Examples include metal catalysts such as platinum and nickel, hydrogen gas or hydrazine, and zinc and nickel-aluminum alloys in the presence of a base. Examples of bases (deacylating agents) to coexist in the reaction solution include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and diethylamine.

Triethylamine, hydrazine, etc. can be mentioned. In this case, hydrazine serves not only as a base but also as a hydrogen donor to the metal catalyst and as a protector for aldehyde groups.

This reaction is carried out in a solvent that is stable against alkali and catalytic hydrogenation, such as water, alcohols such as methanol, ethanol, propatool, isopropanol, 1-butanol, ether, tetrahydrofuran, dioxin, etc. -n. monoglyme etc.]-dels, such as monoglyme.

The 4-human 1]xindole produced in this way is extracted with a solvent. It can be easily separated from the reaction mixture and purified by conventional separation means such as S reduction, F1 reduction, distillation, washing, recrystallization, and chroma 1 filtration.

The 0-allylphenylnispur derivative of the present invention is extremely easy to synthesize and purify, and by using this derivative, 4-human[]xiindole can be produced from m-aminophenol at low cost and in high yield. IFJ can be prepared (the yield of 4-hydroxyindole when R=Me starting from IIl-amine phenol is about 30-60%). In the case of 1) using 2-ditro-6-hydroxyltoluene as the starting material in the conventional method, no bediazotization reaction is involved,
It is advantageous for the T industry because the yield is improved and expensive raw materials are not used. Also, since there is no need to use compounds that are difficult to handle, it is easy to clean the work surface. can.

Claims (1)

[Claims] (1) 0-allylphenyl ester derivative represented by the following general formula (A). ▲There are mathematical formulas, chemical formulas, tables, etc.▼(A) (In the formula, X represents a halogen atom, R represents a lower alkyl group, and R' represents hydrogen or RCO).