Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Statutory Invention Registration
1997-01-09
2001-12-04
Poon, Peter M. (Department: 3641)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
C544S359000, C544S363000, C544S366000, C544S369000, C544S372000, C544S373000, C544S376000, C544S391000, C544S398000, C544S402000, C544S410000
Statutory Invention Registration
active
H0002007
ABSTRACT:
The present invention relates to methods for controlling insects. In particular, it relates to control by application of certain N-heterocyclylalkyl- or N-[(polycyclyl)alkyl]N′-substituted piperazine derivatives to locus where insect control is needed. While not all compounds of the class are novel, the use of the compounds of the invention as insecticides is heretofore unknown.
It has now been found that compounds of the following structure and their agriculturally acceptable salts are active as insecticides:
where:
A and B are independently selected from lower alkyl;
U is selected from lower alkyl, lower alkenyl, CH—Z, where Z is independently selected from hydrogen, lower alkyl, lower cycloalkyl, and phenyl;
R is selected from phenyl, optionally substituted with halogen, lower alkyl, lower alkoxy, phenyl, or phenoxy, and from polycyclyl, optionally substituted with halogen, lower alkyl, or lower alkoxy, where polycyclyl is a dibenzocyclo(C
5-8
)alkyl; and
where R
3
and R
4
are independently selected from phenyl, optionally substituted with halogen, lower alky, lower haloalkyl, lower alkoxy, lower haloalkoxy, lower alkenyl, or phenyl;
R
1
is phenyl, naphthyl, tetrazolylphenyl, phenylcyclopropyl, phenoxyphenyl, benzyloxyphenyl, pyridylphenyl, pyridyloxyphenyl, thiadiazolyloxyphenyl, benzothienyl, benzimidazolyl, indolyl, pyrrolyl, or quinolyl, each optionally substituted with halogen, cyano, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy, amino, lower dialkylamino, nitro, lower haloalkylsulfonyloxy, lower alkylcarbonyloxy, lower alkylcarbonylamino, lower alkoxycarbonyl, lower alkoxyalkoxycarbonyl, lower cycloalkylalkoxycarbonyl, lower alkoxyalkylalkoxycarbonyl, lower alkoxycarbonylamino, alkoxythiocarbonylamino, lower alkyldithiocarbonylamino, lower dialkyldioxolylalkoxycarbonylamino, or halophenylamino; or lower alkyl substituted with any one of the foregoing cyclic R
1
groups; or 3-R
2
, where R
2
is
where D, E, and G are independently selected from hydrogen, halogen, cyano, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy, nitro, lower haloalkylsulfonyloxy, lower alkylcarbonyloxy, lower alkylcarbonylamino, arylcarbonylamino, lower alkylcarbonyl, lower alkoxycarbonyl, or D and E taken together may form the group —O(CH
2
)O—, and J is hydrogen or lower alkyl;
m is 2 or 3 and n is 1, 2, or 3; and
halogen is chlorine, fluorine, or bromine, lower means having from 1 to 6 carbon atoms and any aliphatic chain of three or more carbons may be straight or branched.
Preferred compounds are those in which
U is CH
2
;
R is
where R
3
and R
4
are independently selected from chlorophenyl, fluorophenyl, methylphenyl, trifluoromethylphenyl, methoxyphenyl, and trifluoromethoxyphenyl;
R
1
is phenyl, tetrazolylphenyl, pyridylphenyl, pyridyloxyphenyl; each optionally substituted with halogen, cyano, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy, amino, lower dialkylamino, lower alkylcarbonyloxy, lower alkylcarbonylamino, lower alkoxycarbonyl, lower alkoxyalkoxycarbonyl, lower cycloalkylalkoxycarbonyl, lower alkoxyalkylalkoxycarbonyl, or lower alkoxycarbonylamino; or lower alkyl substituted with any one of the foregoing cyclic R
1
groups; or 3-R
2
, where R
2
is
where D is hydrogen, hydroxy, chloro, fluoro, methyl, methoxy, or phenylcarbonylamino; E and G are independently selected from hydrogen, chloro, fluoro, methyl, and methoxy, with the proviso that when R
1
is lower dialkylaminophenyl, R
3
and R
4
are each trifluoromethoxyphenyl;
m and n are 2; and
halogen is chlorine or fluorine, for aliphatic groups lower means having from 1 to 3 carbon atoms and for alicyclic groups lower means having 3 to 6 carbons.
Particularly preferred are those compounds in which
U is CH
2
;
R is
where R
3
and R
4
are independently selected from 4-chlorophenyl, 4-fluorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, and 4-trifluoromethoxyphenyl;
R
1
is phenyl substituted in the 4-position with lower dialkylamino, lower alkoxycarbonylamino, tetrazolyl, pyridyl, or pyridyloxy; each tetrazolyl or pyridyl group optionally substituted with halogen, cyano, lower alkyl, lower haloalkyl, or lower alkoxy; or 3-R
2
, where R
2
is
where D is hydrogen, 4-chloro, 4-fluoro, 4-hydroxy, or 4-phenylcarbonylamino; E is hydrogen, 5-chloro, 5-methyl, or 6-fluoro; G is hydrogen or 5-methoxy;
m and n are 2; and
halogen is chlorine or fluorine, for aliphatic groups lower means having from 1 to 3 carbon atoms and for alicyclic groups lower means having 3 to 6 carbons.
The N-heterocyclylalkyl- or N-[(polycyclyl)alkyl]-N′-substituted piperazine derivatives of the present invention were prepared by methods known to one skilled in the art. A number of synthesis routes were employed in obtaining the targeted compounds.
Synthesis of the piperazine starting materials are depicted in Schema 1. Various R group intermediates were prepared by first reacting an aryl Grignard reagent (A) with a substituted aldehyde (B), for example, 2,4-dichlorobenzaldehyde, to afford the corresponding (substituted diaryl)methanol (C), for example, (2-chlorophenyl)(4-chlorophenyl)methanol. C can also be prepared by reacting substituted benzophenones (D) with sodium borohydride. The diaryl methanol (C) is then treated with thionyl chloride affording a (substituted diaryl)methyl chloride (E), for example, (2-chlorophenyl)(4-chlorophenyl)methyl chloride. The so-prepared diaryl methyl chloride (E) can then be reacted with piperazine to form the N-[(substituted diaryl)methyl]piperazine (F). The piperazine (F) can be reacted with an appropriate halide (G), affording the targeted N-(substituted alkyl)-N′-[(substituted diaryl)methyl]piperazine (H), for example, N-(4-chloroindol-3-yl-methyl)-N′-[(4-chlorophenyl)(2-chlorophenyl)methyl)piperazine. Alternatively, a substituted indole (I) capable of undergoing a Mannich-type reaction is condensed with formaldehyde and the N-substituted piperazine in dioxane and acetic acid to afford the targeted N-(substituted alkyl)-N′-(R-substituted)-piperazine (J), for example, N-(benzo[&bgr;]ythien-3-ylmethyl)-N′-[bis(4-chlorophenyl)methyl]piperazine. Example 1 provides the detailed procedure for this route.
As depicted by Schema 2, those compounds in which Z is other than hydrogen are prepared by first reacting a substituted indole (I) with phosphorus oxychloride and N,N-dimethylformamide, affording the corresponding substituted aldehyde (K). K is in turn condensed with N-[(substituted diaryl)-methyl]piperazine (F) to form the imine and then reacted with the appropriate alkyl or aryl magnesium halide, for example, phenyl magnesium chloride, affording the targeted N-[(alkyl)(substituted indole)alkyl]- or N-[(aryl)(substituted heterocyclyl)alkyl]-N′-[(substituted diaryl)methyl]piperazine (L), for example, N-[(phenyl)(4-chloroindol-3-yl)methyl]-N′-[bis(4-chlorophenyl)-methyl]piperazine. The substituted indole (I) can also be reacted with an aldehyde and N-[(substituted diaryl)methyl]piperazine (F) under acidic conditions, affording the targeted N-[(alkyl)(substituted heterocyclyl)alkyl]- or N-[(aryl)(substituted heterocyclyl)alkyl]-N′-[(substituted diaryl)methyl]piperazine (L). Examples 2 and 4 provide detailed procedures for this route.
Compounds having the F structure are particularly useful intermediates. The compound with R
3
and R
4
each trifluoromethoxyphenyl, i.e., N-[bis(4-trifluoromethoxyphenyl)methyl]piperazine, is thought to be novel and has the following NMR spectrum, proton assignment in ppm in CDCl
3
: 2.41 (m, 4H); 2.54 (d of m, 2H); 2.98 (m, 2H); 3.39 (t, 1H); 7.15 (d, 4H); 7.40 (d 4H).
At this point an N-[(substituted diaryl)methyl]piperazine (F) can be reacted with an appropriately substituted aldehyde for example, 4-dimethylaminobenzaldehyde, under acidic conditions and at 100 ° C., affords the targeted N-(substituted alkyl)-N′-[(substitute
Ali Syed F.
Cohen Daniel H.
Cullen Thomas G.
Lyga John W.
Silverman Ian R.
Baker Aileen J.
Ertelt H. Robinson
FMC Corporation
Poon Peter M.
Silverman I. Robert
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