Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-03-29
2001-01-30
Kight, John (Department: 1612)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06180801
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for manufacturing a 3-isochromanone useful as an intermediate of medicals or agricultural chemicals, and a method for manufacturing a cyano compound which can be used as a starting material in the manufacturing method of 3-isochromanones.
BACKGROUND OF THE INVENTION
For manufacturing a 3-isochromanone represented by the later described formula (II), some different methods have been proposed. For example, JP-A-9-67364 (the term “JP-A” as used herein means an “unexamined published Japanese patent application”) discloses a method of reacting &agr;,&agr;′-dihalogeno-o-xylene with carbon monoxide and water in the presence of a hydrogen halogenide scavenger and a-complex catalyst containing a metal such as palladium. Furthermore, A. Cowell et al have reported that 3-isochromanone is synthesized by reacting o-bromomethylbenzyl alcohol with carbon monoxide in the presence of a palladium complex catalyst (JACS., 102, 4191 (1980)).
Also, in some methods hitherto proposed, 3-isochromanone is synthesized by the Baeyer-Villiger oxidation reaction using 2-indanone as a starting material. More specifically, A. Chatterjee et al, P. Cottet et al and C. Kocch et al disclose a method of synthesizing 3-isochromanone by reacting 2-isodandne with a metachloroperbenzoic acid (see,
Synthesis,
818 (1981),
Synthesis,
497 (1987),
Synthetic Communication,
19, 829 (1989)). F. G. Mann et al disclose a method of synthesizing 3-isochromanone by reacting &agr;-methoxy-&agr;′-cyano-o-xylene in an aqueous sulfuric acid solution (see,
J. Chem. Soc.,
2819 (1954)). Furthermore, U. Azzena et al disclose a method of synthesizing 3-isochromanone by ring-opening phthalan with a metal lithium, reacting it with carbon dioxide and hydrolyzing the reaction product (see,
Tetrahedron Lett.,
36, 8123 (1995)).
However, these methods are not an industrially useful method because the starting materials are difficult to be synthesized and prevented from the industrial use for general purposes, an expensive reagent or catalyst is necessary to be used or the yield is low.
OBJECT OF THE INVENTION
The object of the present invention is to manufacture a 3-isochromanone represented by formula (II) by an industrially advantageous method in a high yield.
SUMMARY OF THE INVENTION
The present invention relates to a method for manufacturing a 3-isochromanone represented by formula (II):
(wherein R
2
, R
3
, R
4
and R
5
each independently represents a hydrogen atom, a halogen atom, an alkyl group or an alkoxy group (hereinafter, unless otherwise indicated, R
2
to R
5
have the same meanings)), said method comprising hydrolyzing a cyano compound represented by formula (I):
(wherein R
1
represents a hydrogen atom, an alkyl group or an aryl group (hereinafter, unless otherwise indicated, R
1
has the same meaning)) and subjecting the hydrolyzate to intramolecular cyclization.
In the present invention, the hydrolysis is preferably performed in the presence of an acid or an alkali and the intramolecular cyclization is preferably performed in the presence of an acid;
The hydrolysis is preferred to be performed in the presence of an acid.
Moreover, in the above formula (I), R
1
is preferably a hydrogen atom or an alkyl group having from 1 to 9 carbon atoms, and particularly a methyl group, an ethyl group or a 3-n-heptyl group. Further, in the formula (I), R
2
, R
3
, R
4
and R
5
each is preferably a hydrogen atom.
Further, in the present invention, it is preferred that the 3-isochromanone is separated by distillation from the reaction mixture of the intramolecular cyclization.
Still further, the present invention relates to a method for manufacturing a cyano compound represented by formula (I), comprising reacting a monoester compound represented by formula (III):
(X represents a halogen atom (hereinafter, unless otherwise indicated, X has the same meaning)) with a metal cyanide.
In the method for manufacturing a 3-isochromanone according to the present invention, it is particularly preferable that the cyano compound is manufactured by the method described above.
In the present invention, the monoester compound represented by formula (III) is preferably manufactured by reacting an &agr;,&agr;′-dihalogeno-o-xylene compound represented by formula (IV):
with an alkali metal salt or alkaline earth metal salt (hereinafter, collectively called a “carboxylic acid alkali salt”) of a carboxylic acid represented by R
1
COOH (wherein R
1
represents a hydrogen atom, an alkyl group or an aryl group).
In the above, it is preferred that the &agr;,&agr;-dihalogeno-o-xylene compound is reacted in an amount of 2 equivalent or more to the carboxylic acid alkali salt.
Particularly, it is preferable that after the reaction of the &agr;,&agr;′-dihalogeno-o-xylene compound with the carboxylic acid alkali salt, the unreacted &agr;,&agr;′-dihalogeno-o-xylene compound is separated and recovered by distillation from the reaction mixture.
Still more, in the above method, it is preferred that an aprotic polar solvent is added to the reaction system of the &agr;,&agr;′-dihalogeno-o-xylene compound with the carboxylic acid alkali salt.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is described in detail below.
Manufacturing Method of 3-Isochromanones (II)
The cyano compound (I) is hydrolyzed with an alkali such as sodium hydroxide according to reaction scheme (a):
to synthesize a 2-(hydroxymethyl)phenylacetic acid compound (V). The 2-(hydroxymethyl)phenyl acetic acid compound produced is subjected to intramolecular cyclization in the presence of an acid such as hydrochloric acid according to reaction scheme (b):
to synthesize a 3-isochromanone (II). The intermediate product 2-(hydroxymethyl)phenylacetic acid compound (V) may be isolated, optionally purified and then used for the manufacturing of a 3-isochromanone. However, an acid such as hydrochloric acid may be added to the reaction mixture as it is after the hydrolysis to perform intramolecular cyclization according to reaction scheme (c):
Furthermore, the cyano compound (I) may be subjected to hydrolysis and intramolecular cyclization at the same time in the presence of an acid such as hydrochloric acid according to reaction scheme (d):
to synthesize a 3-isochromaonone (II).
The cyano compound (I) is represented by formula (I) and in the formula, R
1
represents a hydrogen atom, an alkyl group or an aryl group. The alkyl group may be either a linear or branched alkyl group. The alkyl group may also be substituted by a group substantially inert to the reaction, such as an aryl group or a halogen atom. The alkyl group is specifically an alkyl group having from 1 to 9 carbon atoms and specific examples thereof include a methyl group, an ethyl group, a n-propyl group, a heptyl group and a 3-n-heptyl group. Examples of the aryl group include a phenyl group and a naphthyl group. The aryl group also includes an aryl group having a substituent such as an alkyl group, an alkoxy group, a carboxyl group or a hydroxyl group. Among them, R
1
is preferably hydrogen atom or an alkyl group having 1 to 9 carbon atoms, particularly, methyl, ethyl or 3-n-heptyl. R
2
, R
3
, R
4
and R
5
each independently represents a hydrogen atom, a halogen atom, an alkyl group or an alkoxy group. Examples of the halogen atom include a fluorine atom, a chlorine atom and a bromine atom. The alkyl group may be either a linear or branched alkyl group. The alkoxy group may be either a linear or branched alkoxy group. Preferably, R
2
, R
3
, R
4
and R
5
each is a hydrogen atom. Specific preferred examples of the cyano compound (I) include [2-(cyanomethyl)phenyl]methyl acetate, [2-(cyanomethyl)phenyl]methyl propionate and [2-(cyanomethyl)phenyl]methyl 2-ethylhexanoate.
The hydrolysis is preferably performed in the presence of an acid or alkali.
In the case where the hydrolysis is performed in the presence of an alkali, the alkali used is sodium hydroxide, potassium hydroxide, calc
Miyata Hideo
Monzen Hiroyuki
Morikawa Kohei
Ooshiro Kimitaka
Covington Raymond
Kight John
Showa Denko Kabushiki Kaisha
Sughrue Mion Zinn Macpeak & Seas, PLLC
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