Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system
Reexamination Certificate
1999-01-29
2001-08-07
Fan, Jane (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Four or more ring nitrogens in the bicyclo ring system
C544S182000, C544S319000, C544S406000, C544S407000, C544S335000, C546S323000, C546S317000, C546S276100
Reexamination Certificate
active
06271372
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a process for the preparation of arylamides of heteroaromatic carboxylic acids by reacting heteroaromatic halogen compounds with carbon monoxide and aromatic amines in the presence of a catalyst and a base. The invention further relates to a novel halogenopyridine as a starting material for the preparation, according to the invention, of an arylamide.
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, but one of the substituents R
1
to R
5
is 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.
Said amides include especially the arylamides of pyridine-, pyrimidine-, pyrazine- and 1,3,5-triazinecarboxylic acids.
2. Background Art
Numerous compounds of the structure of formula I, 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 (International Published Patent Application No. 94/27974, European Published Patent Application No. 0,053,011 and European Published Patent Application No. 0,447,004). The synthesis of these known compounds is conventionally based on the corresponding carboxylic acids or carboxylic acid derivatives (acid chlorides, esters, nitrites), although these are often difficult to obtain and therefore expensive.
BROAD DESCRIPTION OF THE INVENTION
The main object of the invention was to provide an alternative process based on more easily 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 processes and compound 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 a good to almost quantitative yield of the desired products (I) when a complex of palladium with a triphenylphosphine of the general formula:
in which R
8
to R
10
independently of one another are C
1-4
-alkyl, C
1-4
-alkoxy, benzyloxy or fluorine, is present as a catalyst.
The presence of the substituents R
8
to R
10
in the 4-position (para position) of the phenyl groups has proved to be an essential feature here. The corresponding ortho-substituted and meta-substituted compounds, like the unsubstituted triphenylphosphine, give considerably poorer yields or no product at all.
DETAILED DESCRIPTION OF THE INVENTION
Herein, C
1-4
-alkyl is to be understood as meaning any linear or branched primary, secondary or tertiary alkyl groups having up to 4 carbon atoms. 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 quinolinyl. These 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 (alkanesulfanyl) or alkanesulfonyl groups such as methylthio or ethanesulfonyl. Substituted phenyl is to be understood as meaning especially groups such as fluorophenyl, methoxyphenyl, tolyl or trifluoromethyl, wherein the substituents are preferably in the para position.
The halogen compounds (II) used as starting materials are either known compounds or can be prepared analogously to known compounds. Numerous compounds of this type are published, for example, in U.S. Pat. No. 4,254,125 and European Published Patent Application No. 0,001,187. The compound 2-chloro-6-[1-methyl-3-(trifluoromethyl)pyrazol-5-yloxy]pyridine is novel and also forms a subject of the present invention.
The process according to the invention is preferentially suitable for the preparation of amides (I) in which A
2
is nitrogen and forms a pyridine ring with the remaining ring members.
Particularly preferred amides (I) are those in which R
1
is a group of the formula —OR, R being as defined above.
Other preferred amides (I) are those in which A
1
is nitrogen and forms a pyridine ring with the remaining ring members,
those in which A
1
and A
5
are nitrogen and form a pyrimidine ring with the remaining ring members,
those in which A
1
and A
4
are nitrogen and form a pyrazine ring with the remaining ring members,
and those in which A
1
, A
3
and A
5
are nitrogen and form a 1,3,5-triazine ring with the remaining ring members.
In the last four classes mentioned, particularly preferred amides are those in which R
2
is a group of the formula —OR, R being as defined above.
Other preferred amides (I) are those in which R is an optionally substituted phenyl group. This applies especially to the above mentioned amides with a pyridine, pyrimidine, pyrazine or 1,3,5-triazine ring in which R
1
or R
2
is a group of the formula —OR.
Other preferred amides are those in which R
6
is hydrogen and R
7
is an optionally substituted phenyl group.
Preferred halogen compounds (II) are the chlorine compounds (X is Cl).
Particularly preferred triphenylphosphines (IV) are those in which R
8
to R
10
are identical and are C
1-4
-alkoxy or benzyloxy groups.
The triphenylphosphine in which R
8
to R
10
are methoxy groups is very particularly preferred.
The catalytically active palladium phosphine complex is advantageously formed in situ by a process in which palladium in finely divided elemental form (e.g., palladium on activated charcoal), a Pd(II) salt (e.g., the chloride or the acetate) or a suitable Pd(II) complex [e.g., dichlorobis(triphenylphosphine)palladium(II)] is reacted with the phosphine. The particularly preferred palladium source is palladium(II) acetate. The palladium is preferably used in an amount of 0.02 to 0.2 mol percent of Pd(II) or 0.5 to 2 mol percent of Pd(0) (as Pd/C), based in each case on the halogen compound (II). The phosphine is advantageously used in excess (based on Pd), preferably in an amount of 0.2 to 5 mol percent, again based on the halogen compound (II).
The solvents used can be either relatively non-polar, for example, methylcyclohexane, toluene or xylene, or polar, for example, acetonitrile, tetrahydrofuran, pyridine, butyl acetate, N-methylpyrrolidone, methyl isobutyl ketone or N,N-dimethylacetamide. Particularly good results have been achieved with non-polar solvents, especially with methylcyclohexane or xylene.
The base used is preferably a relatively weak base. This does not need to be soluble in the solvent used. Examples of suitable bases are carbonates such as sodium or potassium carbonate, (hydrogen-) phosphates such as tripotassium phosphate, dipotassium hydrogen phosphate or disodium hydrogen phosphate, or acetates such as sodium acetate. Particularly good results have been achieved with sodium carbonate or dipotassium hydrogen phosphate.
The reaction temperature is preferably 800 to 250° C.
The carbon monoxide pressure is preferably 1 to 50 bar.
The halogen compounds (II) are advantageously prepared by reacting a dihalide of the general formula:
in which X is chlorine, bromine or iodine and 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 Z, Z being chlorine, bromine or io
Kalbermatten Georges
Roduit Jean-Paul
Fan Jane
Fisher Christen & Sabol
Lonza AG
LandOfFree
Process for the preparation of arylamides of heteroaromatic... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the preparation of arylamides of heteroaromatic..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of arylamides of heteroaromatic... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2511112