Process for the preparation of arylamides of heteroaromatic...

Details Process for the preparation of arylamides of heteroaromatic... Process for the preparation of arylamides of heteroaromatic...

1997-03-28

2003-10-21

Vollano, Jean F. (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C546S301000, C546S302000, C544S329000, C544S406000

Reexamination Certificate

active

06635766

ABSTRACT:

SUMMARY DESCRIPTION OF THE INVENTION
The invention relates to a process for the preparation of arylamides of heteroaromatic carboxylic acids by the reaction of heteroaromatic halogen compounds with carbon monoxide and aromatic amines in the presence of a catalyst and a base. It further relates to a process for the preparation of arylamides of heteroaromatic carboxylic acids which carry an aryloxy or heteroaryloxy group as a substituent on the heteroaromatic ring, by the reaction of heteroaromatic dihalogen compounds with aromatic or heteroaromatic hydroxyl compounds to give (hetero)aryloxy-substituted heteroaromatic monohalogen compounds, and the further reaction of these compounds with carbon monoxide and aromatic amines in the presence of a catalyst and a base.
The amides which can be prepared according to the invention have the general formula:
in which:
A
1
is nitrogen or CR
1
,
A
2
is nitrogen or CR
2
,
A
3
is nitrogen or CR
3
,
A
4
is nitrogen or CR
4
, and
A
5
is nitrogen or CR
5
,
with the proviso that at least one of the ring members A
1
to A
5
is nitrogen and that two nitrogen atoms are not bonded directly to one another;
R
1
to R
5
, if present, independently of one another are hydrogen, C
1-4
-alkyl or aryl, one of the substituents R
1
to R
5
being a group of the formula —OR, in which R is an optionally substituted aromatic or heteroaromatic radical;
R
6
is hydrogen or C
1-4
-alkyl; and
R
7
is an optionally substituted aromatic or heteroaromatic radical.
Such amides include especially the arylamides of pyridine-, pyrimidine-, pyrazine- and 1,3,5-triazine-carboxylic acids.
BACKGROUND ART
Numerous compounds of the structure of Formula 1, especially those in which one of the substituents R
1
to R
5
is an aryloxy group (—OR) adjacent to a ring nitrogen atom, are important herbicides (WO-A 94/27974, European Published Patent Application No. 0,053,011, and European Published Patent Application No. 0,447,004). These known compounds are conventionally synthesized from the corresponding carboxylic acids or carboxylic acid derivatives (acid chlorides, esters, and nitriles), although these are often difficult to obtain and, consequently, expensive.
BROAD DESCRIPTION OF THE INVENTION
The main object of the invention is to provide an alternative process which is based on more readily obtainable educts. Other objects and advantages of the invention are set out herein or are obvious herefrom to one skilled in the art. The objects and advantages of the invention are achieved by the process of the invention.
The invention involves a process for the preparation of amides of the general formula:
in which
A
1
is nitrogen or CR
1
,
A
2
is nitrogen or CR
2
,
A
3
is nitrogen or CR
3
,
A
4
is nitrogen or CR
4
, and
A
5
is nitrogen or CR
5
,
with the proviso that at least one of the ring members A
1
to A
5
is nitrogen and that two nitrogen atoms are not bonded directly to one another;
R
1
to R
5
, if present, independently of one another are hydrogen, C
1-4
-alkyl or aryl, one of the substituents R
1
to R
5
being a group of the formula —OR, in which R is an optionally substituted aromatic or heteroaromatic radical;
R
6
is hydrogen or C
1-4
-alkyl; and
R
7
is an optionally substituted aromatic or heteroaromatic radical, comprising reacting a halogen compound of the general formula:
in which A
1
to A
5
are as defined above and X is chlorine, bromine or iodine, with carbon monoxide and an amine of the general formula:
R
6
—NH—R
7
  III,
in which R
6
and R7 are as defined above, in the presence of a complex of palladium with a diphosphine of the general formula:
R
8
R
9
P—[CH
2
]
n
—PR
10
R
11
  IV,
in which R
8
to R
11
independently of one another are phenyl or substituted phenyl and n is 3 or 4, and with a base.
Preferably, in Formulae I and II, A
2
is nitrogen and part of a pyridine ring. Preferably, in Formulae I and II, R
1
is a group of the formula —OR.
Also preferably, in Formulae I and II, A
1
is nitrogen and part of a pyridine ring.
Also preferably, in Formulae I and II, A
1
and A
5
are nitrogen and part of a pyrimidine ring.
Also preferably, in Formulae I and II, A
1
and A
4
are nitrogen and part of a pyrazine ring.
Preferably, in Formulae I and II, A
1
, A
3
and A
5
are nitrogen.
In each of the last four preferable embodiments listed just above, preferably, in Formulae I and II, R
2
is a group of the formula —OR.
Preferably, in Formulae I and II, R is an optionally substituted phenyl group, in Formulae I and III, R
6
is hydrogen and R
7
is an optionally substituted phenyl group.
Preferably, in Formula II, X is chlorine.
Preferably, the diphosphine (IV) used is 1,3-bis(diphenylphosphino)propane or 1,4-bis(diphenylphosphino)butane.
The invention also involves a process for the preparation of amides of the general formula:
in which A
1
to A
5
, R
6
and R
7
are as defined above, comprising, in a first step, reacting a dihalide of the general formula:
in which A
1
to A
5
are as defined above with the proviso that one of the radicals R
1
to R
5
on a carbon atom adjacent to a ring nitrogen atom is replaced with Z, Z is chlorine, bromine or iodine and X independently thereof is chlorine, bromine or iodine, with an aromatic or heteroaromatic hydroxyl compound of the general formula:
R—OH  VI,
in which R is as defined above, to give a (hetero)aryloxy halogen compound of the general formula:
in which A
1
to A
5
, and X are as defined above, and, in a second step, reacting said product with carbon monoxide and an amine of the general formula:
R
6
—NH—R
7
  III,
in which R
6
and R
7
are as defined above, in the presence of a complex of palladium with a diphosphine of the general formula:
R
8
R
9
P—[CH
2
]
n
—PR
10
R
11
  IV
in which R
8
to R
11
and n are as defined above and with a base.
DETAILED DESCRIPTION OF THE INVENTION
It has been found that halogen compounds of the general formula:
in which A
1
to A
5
are as defined above and X is chlorine, bromine or iodine, react directly with carbon monoxide and a primary or secondary amine of the general formula:
R
6
—NH—R
7
  III,
in which R
6
and R
7
are as defined above, in the presence of a base, to give good to almost quantitative yields of the desired products (I) if a complex of palladium with a diphosphine of the general formula:
R
8
R
9
P—[CH
2
]
n
—PR
10
R
11
  IV
is present as a catalyst. In the general formula IV, R
8
to R
11
independently of one another are phenyl or substituted phenyl and n is 3 or 4.
Herein, C
1-4
-alkyl is to be understood as meaning any linear or branched primary, secondary or tertiary alkyl group having up to 4 carbon atoms e.g., methyl or ethyl. Herein, aromatic or heteroaromatic radicals are to be understood as meaning especially monocyclic or polycyclic systems, such as, phenyl, naphthyl, biphenylyl, anthracenyl, furyl, pyrrolyl, pyrazolyl, thiophenyl, pyridyl, indolyl or quinolinlyl. These radicals can carry one or more identical or different substituents, for example, lower alkyl groups such as methyl, halogenated alkyl groups such as trifluoromethyl, lower alkoxy groups such as methoxy, or lower alkylthio (alkanesulphanyl) or alkanesulphonyl groups such as methylthio or ethanesulphonyl. Substituted phenyl is understood as meaning especially groups such as (p-)fluorophenyl, (p-)tolyl or (p-)trifluoromethylphenyl.
The halogen compounds (II) used as starting materials are known compounds or can be prepared analogously to known compounds. Numerous compounds of this type have been published, for example, in U.S. Pat. No. 4,254,125 and European Published Patent Application No. 0,001,187.
The halogen compounds (II) in which the group of the formula —OR is bonded to a carbon atom adjacent to a ring nitrogen atom are advantageously prepared by a process in which a dihalide or the general formula:
in which A
1
to A
5
are as defined above, with the proviso that one of the radicals R
1
to R
5
on a carbon atom adjacent to a ring nitrogen atom is replaced

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