JPS626543B2 - - Google Patents

Description

[Detailed Description of the Invention] The present invention relates to the general formula () (In the formula, R represents a hydrogen atom or a lower alkyl group having 1 to 2 carbon atoms, and X represents a carboxy group, a carbalkoxy group, or a cyano group.)

The compound represented by the general formula () is an anti-inflammatory agent,
Formula () with excellent activity as an analgesic It is a useful intermediate in the production of 1-oxo-2-{p-[(α-methyl)carboxymethyl]-phenyl}-isoindoline (indoprofen), which itself has anti-inflammatory properties. It is an industrially useful compound that has pharmacological effects such as analgesic effect.

The method for synthesizing the benzylidene derivative () of the present invention is expressed by the formula () O-phthalaldehyde acid represented by and the general formula () (In the formula, R and X represent the same meanings as above) and water, methanol,
Ethanol, tetrahydrofuran, dioxane,
The target compound can be obtained in good yield by reacting in a solvent such as benzene, toluene, xylene, diglyme (methanol and ethanol are particularly preferred) at room temperature or under heating.

The benzylidene derivative thus obtained is introduced into indoprofen and its derivatives represented by the formula () by using a reducing agent such as sodium borohydride or potassium borohydride in a solvent such as methanol or ethanol. I can do it.

Next, the present invention will be explained with reference to Examples, but the present invention is not limited thereto.

Example 1 1.5 g of O-phthalaldehydic acid and 1.3 g of P-aminobenzyl cyanide were added to 20 ml of ethanol, heated and dissolved, and then stirred at room temperature for 10 minutes to precipitate crystals. The formed crystals are collected, dried, and recrystallized with ethanol to form colorless prism crystals p-(o
2.6 g of -carboxybenzylidene)-amino-phenylacetonitrile were obtained.

The melting point, infrared absorption spectrum, mass spectrum, and elemental analysis values of this substance were as follows.

Melting point 208-209℃ Infrared absorption spectrum νc=0 1757cm ^-1 νcN 2240, 1522cm ^-1 Mass spectrum M ⁺ 264 Elemental analysis value C ₁₆ H ₁₂ N ₂ O ₂ theoretical value C: 72.71 H: 4.58 N: 10.60 Actual value C: 72.78 H: 4.52 N: 10.56 Example 2 1.5 g of O-phthalaldehydic acid and 1.5 g of p-aminophenyl acetic acid were added to 20 ml of methanol at room temperature.
After stirring for 30 minutes, the solvent was concentrated under reduced pressure. The precipitated crystals were collected and dried to obtain 2.7 g of colorless prismatic crystals of p-(o-carboxybenzylidene)-amino-phenylacetic acid.

The melting point, infrared absorption spectrum, mass spectrum, and elemental analysis values of this substance were as follows.

Melting point 214-215℃ Infrared absorption spectrum νc=0 1730, 1707cm ^-1 νcN 1524cm ^-1 Mass spectrum M ⁺ 283 Elemental analysis value C ₁₆ H ₁₃ NO ₄ Theoretical value C: 67.84 H: 4.63 N: 4.95 Actual value C: 67.93 H: 4.58 N: 5.03 Example 3 1.5 g of O-phthalaldehydic acid and p-amino-
(α-Methyl)-phenylacetic acid ethyl ester 1.9
After adding g to 20 ml of methanol and stirring at room temperature for 30 minutes, the solvent was concentrated under reduced pressure. When the precipitated crystals are collected and dried, colorless prism crystals p-(o
-Carboxybenzylidene)-amino(α-methyl)phenyl acetic acid ethyl ester (3.2 g) was obtained.

The melting point, infrared absorption spectrum, mass spectrum, and elemental analysis values of this substance were as follows.

Melting point 138-140℃ Infrared absorption spectrum νc=0 1745, 1725cm ^-1 νcN 1528cm ^-1 Mass spectrum M ⁺ 325 Elemental analysis value C ₁₉ H ₁₉ NO ₄ Theoretical value C: 70.14 H: 5.89 N: 4.31 Actual value C: 70.08 H: 5.94 N: 4.29 Example 4 1.5 g of O-phthalaldehydic acid and p-amino-
(α-methyl)phenylacetic acid 1.65g in methanol
After adding to 20 ml and stirring at room temperature for 30 minutes, the solvent was concentrated under reduced pressure. The precipitated crystals were collected and dried to obtain 2.9 g of colorless prismatic p-(o-carboxybenzylidene)-amino-(α-methyl)-phenylacetic acid.

The melting point, infrared absorption spectrum, mass spectrum, and elemental analysis values of this substance were as follows.

Melting point 185-187℃ Infrared absorption spectrum νc=0 1740, 1710cm ^-1 νcN 1522cm ^-1 Mass spectrum M ⁺ 297 Elemental analysis value C ₁₇ H ₁₅ NO ₄ Theoretical value C: 68.67 H: 5.08 N: 4.71 Actual value C: 68.52 H: 5.16 N: 4.87 Reference example p-(o-carboxybenzylidene)-amino-
(α-Methyl)-phenylacetic acid 1.5g in methanol
Suspend in 30 ml of sodium borohydride under ice cooling.
0.38g was added in several portions. Next, the mixture was returned to room temperature and stirred for 3 hours, and then the solvent was distilled off under reduced pressure. 50 ml of water was added to the residue, and a small amount of acetic acid was added to form an acidic solution. When the precipitated crystals are collected, dried, and recrystallized with ethanol, colorless crystals of 1-oxo-2-
1.3 g of {p-[(α-methyl)carboxymethyl]-phenyl}-isoindoline was obtained.

The melting point, infrared absorption spectrum, and mass spectrum of this substance were as follows.

Melting point 214-215℃ Infrared absorption spectrum νc=0 (KBr) 1683cm ^-1 Mass spectrum M ⁺ 281

Claims (1)

[Claims] 1. General formula A benzylidene derivative represented by the formula (wherein R represents a hydrogen atom or a lower alkyl group having 1 to 2 carbon atoms, and X represents a carboxyl group, a carbalkoxy group, or a cyano group).