JPS5970671A - Arylcarbostyryl derivative - Google Patents

Abstract

NEW MATERIAL:The compound of formula (R is H, alkyl or aralkyl; X is -O- or -NH-; n is 4-9; Ar is aromatic ring). EXAMPLE:1-Phyenyl-4-methyl-6-methoxy-3,4-dihydrocarbostyryl. USE:Raw material of pharmaceuticals, agricultural chemicals, dyes, additives, reducing agents, and fluorane compounds, and intermediate of antioxidants and photographic developers. PROCESS:The objective compound of formula can be prepared by reacting an alkoxydihydrocarbostyryl with an aryl halide, preferably iodide or bromide in the presence of a catalyst such as copper compound, Na2CO3, K2CO3, etc., if necessary in a polar solvent such as dimethylformamide, at 150-235 deg.C for 45min-32hr.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to carbostyryl derivatives, and in particular to arylcarbostyryl derivatives having an aryl group r at the l-position and a hydroxy group, alkoxy group, or alkylamino group r at the 6-position. Dihydrocarbostyril and its derivatives are compounds that have recently attracted attention for purposes such as medicines, agricultural chemicals, dyes, and additives.

For example, JP-A No. 5μm 70.112, same! Hirota o
, itJ issue, same j, t-33, 0/5' issue, J, Or
g, Chem,, tls 261! (/ri10), J
, Heterocyclic Chem, /7 /
Application examples are disclosed in US Pat. No. 32 or 100, etc.

The compounds of the present invention relate to derivatives of carbostyryl and dihydrocarbostyryl having an aryl group r at the l-position, and in addition to the above-mentioned uses, they can also be used as reducing agents, raw materials for fluoran compounds, antioxidants, and intermediates for photographic developers. , is a compound useful as various additives, etc. In particular, it has the advantage that it can be obtained in good yield with fewer steps from p-aminophenol or anisidine, which are major raw materials in the chemical industry.

It is known that carbostyril can be synthesized by various reactions such as the 2Knorr method, and the preparation of the corresponding dihydro compound by the reduction reaction of carbostyril has already been studied in detail.

The carbostyryl derivative according to the present invention has the following general formula (1
).

Ar is 6'r: sAr represents an aromatic ring.

Among the carbostyril derivatives represented by the above general formula (1), those represented by the following general formula (II)t or (I[) are preferred.

Ar In the above formula, R is a hydrogen atom, an alkyl group or an aralkyl group,
Is X 10- or -N-1Ar an aromatic ring? represent.

The compound of the present invention having an aryl group at the l-position and an oxy, alkoxy, or alkylamino group at the -position is synthesized by the following method. For dihydro compounds having an alkoxy group r at the mg-position, copper compounds, potassium carbonate, sodium carbonate, etc. can be added to the corresponding alkoxydihydrocarbostyryl. As a catalyst, an aryl halide, preferably an iodide or a bromide, is used, if necessary, in the presence of a polar solvent such as dimethylformamide or N-methylpyrrolidone. From OoC to λJj0C, Pi! It is synthesized by a gentle reaction for 3.2 minutes to 3.2 hours.

Further, at this time, the alkyl portion of the alkoxy group does not participate in this reaction at all. Therefore, in the present invention, the alkyl of the alkoxy group is not particularly limited, but includes groups having up to r carbon atoms, such as benzyl, coethylhexyl, cyclohexyl, 5ec-amyl, butyl, propyl, ethyl, and methyl groups. Ethyl, methyl groups, and the like are particularly advantageous in terms of ease of availability as industrial raw materials, raw material cost, and ease of handling due to the crystallinity of the resulting compound.

Are you familiar with the reaction between aryl halides and anilines? Is the halide compound unsubstituted or substituted, such as halogen, alkyl, alkoxy, nitro, etc.? It has been confirmed that the reaction proceeds smoothly even when there are multiple units. In particular, in the present invention, the amine group is in the form of an acylamino compound, which is activated for the reaction with the aryl halide, and it can be used under milder conditions than the usual reaction between aniline and aryl halide. It has the advantage that the reaction proceeds smoothly.

Therefore, the Ar group is not particularly limited, and any one of benzene ring, naphthalene ring, heterocycle, etc. can be used. Substituent? If it has, it has / or more of a halogen atom (particularly a chlorine atom), an alkyl group such as methyl, ethyl, or trifluoromethyl, an alkoxy group such as methoxy or ethoxy, a nitro group, or a dialkylamino group. Good too. Specific skeletons include λ, 6-dicalphenyl, +216-dichloro-methylphenyl,
J-)! J Fluoromethylphenyl, g-chlorophenyl, Hiro-ethylphenyl, Hiro-methoxyphenyl 1.2
, 41-') chlorphenyl, 3-nitrophenyl,
Examples include those containing benzene such as nitrophenyl. These bromides and iodides are known and the raw materials are easily available.

(2) The same synthesis method as described above is applied to methylcarbostyryl having an alkoxy group r at the 6-position.

In addition, in this compound, the 6-negative ring portion containing the nitrogen atom is λ
- Oxypyridine derivatives are thought to give ethers. But the product? Analysis confirmed that the main reaction was proceeding on nitrogen atoms, contrary to expectations.

(3) Oxy group at the 6-position? The carbostyryl derivatives have the corresponding alkoxylated compounds, aluminum chloride,
Obtained by hydrolysis with boron halides, amines, etc.

(4) Alkylamino group at 6-position? The compound has 6
Oxy group at - position? It is synthesized by a substitution reaction of a compound with an amine compound. The conversion of phenolic hydroxyl groups into aminated compounds has been well known for a long time as the Bucherer reaction. It is also known that in the reaction of a compound having a phenol hydroxide group with an amine, a catalyst such as zinc chloride, disulfanilic acid sulfate, ursium chloride, or iodine may be used in combination, if necessary.

These conventionally known techniques can also be skillfully applied to the synthesis of the compounds of the present invention. As the alkyl group portion of the alkylamino group, a skeleton having the following number of carbon atoms as described in (1) above is effective.

The above-mentioned synthesis method is as shown in the following example: (1) Aryl Mk may be introduced after decomposition of a hydroxyl group-containing compound; Methods such as reduction with a catalyst such as iron, cobalt, or platinum to induce a dihydro form can also be applied.

In the above general formula, n represents μ or 6r, especially μm
Methyl carbostyril derivatives are preferred over 3-methyl carbostyryl derivatives because of ease of synthesis and ease of handling due to crystallinity.

Examples below? ≦' Example〃In a 2-screw tube equipped with a λ stirrer and a reflux condenser, Hiro-methyl-A-methoxy-3,4A-dihydrocarbostyryl/6v1 iodine benzene jrnl,)Re Kari13.
-ty and copper aQ, ≠2r. While stirring/
y117. ．． 23 o 0CK4tQrks'jhold RL,, it leaks when it's hot. F liquid? If left alone, l-phenyl-μm methyl-6-medoxy3. Hiro-dihydrocarbostyril precipitates as crystals. Melting point 2! ~6
°C (recrystallized from ligroin) molecular weight 2b72b7 (
, yield rj% Example 2 Inner volume -200 ml autoclave/-phenyl-
l-Methyl-6-medoxy 31μm dihydrocarbostyryl-ol-butylamine. mlk weighing/ζ. After replacing with nitrogen gas, it was kept at CORO 00 (:) for 75 hours while stirring.When it was allowed to cool to room temperature, crystals precipitated. Molecule i2jj (Ms) yield 60%, elemental analysis carbon hydrogen nitrogen calculated values 7. f, 17 j, 7 j, !2 actual measurements 7 j, Rihiro !, 16 !, from the results of J Nikorella 7-phenyl-Hiro-methyl-6-oxy-3,Hiro-
It was confirmed that dihydrocarbostyril was produced. This compound can also be synthesized by treating the corresponding alkoxy compound with boron tribromide as a busy solvent.

Example 3 From the reaction mixture obtained in Example 7, 7-phenyl-l-methyl-oxy-j,4(-dihydrocarphos f!
J LukP separated. The distillate was separated by chromatography using chloroform-acetone as a silica gel carrier, and the solvent was removed under reduced pressure to obtain M [melting point Pμ-2].
Crystals of 6,j″c (can be recrystallized from ethyl ether) were precipitated.Yield 7 Molecular weight 3or (MS) Elemental analysis value % Carbon Hydrogen Nitrogen Actual value 77,jta 7.Iuta,or calculated value
77.5'/ 7.16 ta, // These results and analysis used for NM method 〃) The product is l-phenyl-
This compound, which was found to be q-methyl-6-7'' thylamino-3,hiro-dihydrocarbostyryl, was produced by the reaction of the phenolic compound isolated in Example 1 with an amine. The thus obtained compounds with phenolic hydroxyl groups or active amine groups are highly reactive and contain alkyl, aralkyl or aryl hubrides, acid chlorides, epoxy compounds, diedine, ethylene carbonate, isocyanates, aromatic or aliphatic compounds. Easily reacts with group amines, etc. to form ethers, esters,
It can be derived into urethane, amine, amide, urea, etc.

Example 4 Reaction similar to Example 1? The test was carried out using Hiro-methyl-6-medoxycarbostyryl r. If reaction P is left to stand after completion, the whole will solidify.

When extraction is performed using an ethereal solvent, crystals will precipitate. Melting point: ioo 0c, molecular weight -6j (M8) Elemental analysis value: Carbon Hydrogen Nitrogen Calculated value: 76.96! , 70 t, ko is the measured value 'yt, ri r, ji s, 3゜ This compound is l-phenyl-μm methyl-6-medoxycarbostyryl and 4.6゜

Claims (1)

[Scope of Claims] Arylcarbostyryl derivative r represented by the following general formula (I) In the above formula, R is a hydrogen atom, an alkyl group or an aralkyl group,
X is 10-, fl-N-1n is μ or 4, A 1 is an aromatic ring, and O