Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-05-13
2003-08-05
Owens, Amelia (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C549S466000
Reexamination Certificate
active
06603025
ABSTRACT:
The present invention relates to a novel process for preparing known benzofuranone oximes, and to a novel process for preparing known benzofuranyl alkanoates which are used as intermediates in the synthesis sequence.
It is already known that benzofuranone oximes of the formula (D) can be obtained by the following synthesis sequence:
In the first step of the synthesis, a salicylic acid derivative of the formula (A) (compare, for example, J. Chem. Soc. 1932, 1380; Chem. Ber. 33, 1398, (1900); Chem. Ber. 46, 3370, (1913)) is heated with acetic anhydride and sodium acetate, if appropriate in the presence of glacial acetic acid (compare, for example, Adv. Het. Chem. 18, 434 and J. Chem. Soc. Perkin Trans, I, 1984, 1605-1612). The disadvantages of the described processes are firstly the unsatisfactory yields of the corresponding benzofuranyl acetate of the formula (B) and, in particular, the by-product of the formula (E) which is formed in the reaction:
This by-product, which is formed in amounts of up to 10%, is very difficult to separate from the desired product and is thus very particularly disadvantageous for the known processes for preparing benzofuranyl acetates of the formula (B).
In the next step, the benzofuranyl acetates of the formula (B) are hydrolyzed to the benzofuranones of the formula (C) (compare, for example, J. Chem. Soc. Perkin Trans, I, 1984, 1609). This step likewise gives only unsatisfactory yields. Furthermore, the benzofuranones of the formula (C) are chemically unstable and cannot be stored (compare, for example, The Chemistry of Heterocyclic Compounds, 29, 226).
The synthesis of the benzofuranone oximes of the formula (D) from the benzofuranones of the formula (C) and appropriate hydroxylamine derivatives has likewise been described (compare, for example, Chem. Ber. 33, 3178 (1900) and EP-A 846691). This process step has the disadvantage that the unstable benzofuranones are used as starting materials.
It has now been found that
a) Benzofuranone oximes of the formula (I),
in which
R
1
represents hydrogen or alkyl and
R
2
, R
3
, R
4
and R
5
are identical or different and independently of one another each represents hydrogen, alkyl, alkoxy, halogenoalkyl or halogen
are obtained when benzofuranyl alkanoates of the general formula (II),
in which
R
2
, R
3
, R
4
and R
5
are each as defined above and
R
6
represents alkyl, are hydrolyzed using an acid, if appropriate in the presence of a diluent, and the resulting benzofuranone of the formula (III),
in which
R
2
, R
3
, R
4
and R
5
are each as defined above, is reacted without work-up with a hydroxylamine derivative of the formula (IV),
H
2
N—O—R
1
(IV)
in which
R
1
is as defined above,
or an acid addition complex thereof, if appropriate in the presence of a diluent and if appropriate in the presence of a buffer medium.
The formula (II) provides a general definition of the benzofuranyl alkanoates required as starting materials for carrying out the process according to the invention. Preference is given to using compounds of the formula (II), in which
R
2
, R
3
, R
4
and R
5
are identical or different and independently of one another each represents hydrogen, alkyl or alkoxy having in each case 1 to 4 carbon atoms, halogenomethyl or halogen and
R
6
represents alkyl.
Particular preference is given to preparing benzofuranyl alkanoates of the formula (II), in which
R
2
, R
3
, R
4
and R
5
are identical or different and independently of one another each represents hydrogen, methyl, methoxy, t-butyl, trifluoromethyl, fluorine, chlorine or bromine, where very particularly preferably at least three of the substituents R
2
to R
5
represent hydrogen, and
R
6
represents methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl.
R
6
generally particularly preferably represents methyl or ethyl.
The benzofuranyl alkanoates of the formula (II) are known and can be prepared by known methods (compare, for example, Adv. Het. Chem. 18, 434 and J. Chem. Soc. Perkin Trans, I, 1984, 1605-1612).
It is extremely surprising that the benzofuranone formed as intermediate in the reaction mixture does not suffer partial decomposition in the form of oxidation or polymerization, as described in the literature, but reacts immediately with the hydroxylamine derivative of the formula (IV) to give the desired end product in very high purity.
The process a) according to the invention has a number of advantages. Thus, benzofuranoneamines can be prepared in high yields and purities from easily obtainable starting materials under technically simple conditions.
The formula (IV) provides a general definition of the hydroxylamine derivatives and their acid addition complexes furthermore required as starting materials for carrying out the process a) according to the invention. In this formula (IV), R
1
represents hydrogen or methyl. Preferred acid addition complexes of compounds of the formula (IV) are the hydrochlorides or hydrogen sulphates or sulphates.
The preferred compound of the formula (IV) is O-methylhydroxylamine. Particular preference is given to hydroxylamine or its acid addition complexes.
The hydroxylamine derivatives of the formula (IV) and their acid addition complexes are known chemicals for synthesis.
It has furthermore been found that
b) benzofuranyl alkanoates of the general formula (II) are obtained when salicylic acid derivatives of the formula (V),
in which
R
2
, R
3
, R
4
, R
5
are each as defined above
are reacted with aliphatic acid anhydrides of the formula (VI)
in which
R
6
is as defined above or aliphatic acyl chlorides of the formula (VII),
in which
R
6
is as defined above in the presence of a catalyst.
It is extremely surprising that the formation of the by-product described in the literature, which is troublesome and difficult to remove, is suppressed virtually completely.
The process b) according to the invention has a number of advantages. Thus, benzofuranyl alkanoates can be obtained in high yields and purities from easily obtainable starting materials under technically very simple conditions.
The formula (V) provides a general definition of the salicylic acid derivatives required as starting materials for carrying out the process b) according to the invention. In this formula (V), R
2
, R
3
, R
4
and R
5
each preferably or in particular have those meanings which have already been mentioned in connection with the description of the compounds of the formula (II) as being preferred or as being particularly preferred for R
2
, R
3
, R
4
and R
5
.
The salicylic acid derivatives of the general formula (V) are known and can be prepared by known methods (compare, for example, J.Chem. Soc. 1932, 1380; Chem. Ber. 33, 1398, (1900); Chem. Ber. 46, 3370, (1913)).
The formula (VI) provides a general definition of the carboxylic anhydrides furthermore required as starting materials for carrying out the process b) according to the invention. In this formula (VI), R
6
preferably or in particular has that meaning which has already been mentioned in connection with the description of the compounds of the formula (IV) as being preferred or as being particularly preferred for R
6
.
The formula (VII) provides a general definition of the carbonyl chlorides furthermore alternatively required as starting materials for carrying out the process b) according to the invention. In this formula (VII), R
6
preferably or in particular has that meaning which has already been mentioned in connection with the description of the compounds of the formula (II) as being preferred or as being particularly preferred for R
6
.
The carboxylic anhydrides of the formula (VI) and the carbonyl chlorides of the formula (VII) are known chemicals for synthesis.
Suitable diluents for carrying out the first and the second step of the process a) according to the invention are inert organic solvents. By way of example and by way of preference, these include ethers, such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyeth
Decker Matthias
Gallenkamp Bernd
Gayer Herbert
Gerdes Peter
Hübsch Walter
Harmuth Raymond J.
Henderson Richard E. L.
Owens Amelia
LandOfFree
Method of production of benzofuranone oximes does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of production of benzofuranone oximes, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of production of benzofuranone oximes will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3126220