Process for the preparation of 4-haloalkylnicotinonitriles

Details Process for the preparation of 4-haloalkylnicotinonitriles Process for the preparation of 4-haloalkylnicotinonitriles

2001-12-13

2003-04-01

Rotman, Alan L. (Department: 1625)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C546S250000, C546S251000, C546S318000

Reexamination Certificate

active

06541640

ABSTRACT:

CROSS-REFERENCE TO PRIORITY APPLICATIONS
This application claims priority under 35 U.S.C. §119 of DE 1006,967.3, filed Dec. 13, 2000, DE 10120819.7, filed Apr. 27, 2001 and DE 10144411.7, filed Sep. 11, 2001, all of which are incorporated by reference herein in their entireties and relied upon.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a process for the preparation of 4-haloalkyl-3-pyridinecarbonitriles (4-haloalkylnicotinonitriles) and their further reaction to give 4-haloalkylnicotinic acid derivatives having insecticidal activity.
2. Background Art
4-Haloalkylnicotinamides are useful starting substances for the preparation of pesticides, such as are described, for example, in WO-A 98/57969, EP-A 0580374 and DE-A 10014006.
These compounds can be prepared in two stages from 4-haloalkylnicotinic acids, whose synthesis is described, for example, in EP-A 0744400.
SUMMARY OF THE INVENTION
A simple process has surprisingly now been found for the preparation of 4-haloalkylnicotinonitriles having formula (I) below, from which 4-haloalkylnicotinic acids can be obtained in one step by hydrolysis.
The invention therefore relates to a process for the preparation of 4-haloalkylnicotinonitriles, having the formula (I):
wherein R
F
is (C
1
-C
4
)-haloalkyl, preferably CF
3
, said process comprising:
(a) reacting a 3-amino-1-haloalkyl-2-propen-1-one having the formula (II):
R
f
—C(O)—CH═CH—NH
2
  (III)
 wherein R
F
is defined as above, in a condensation reaction with at least one compound having a formula selected from the group consisting of (III), (IV), (V), (VI) and (VII):
(R
1
Z)CH═CH—CN  (III)
(R
1
Z)
2
CH—CH
2
—CN  (IV)
Hal-CH═CH—CN  (V)
Hal
2
CH—CH
2
CN  (VI)
HC≡C—CN  (VII)
 wherein R
1
is alkyl, Hal is Cl or Br and Z, which is identical or different, is O, S, NR
1
or OCO;
 to afford at least one compound selected from the group consisting of (VIII), (IX) and (X):
R
F
—C(O)—CH═CH—NH—CH═CH—CN  (VIII)
R
F
—C(O)—CH═CH—NH—CH(ZR
1
)—CH
2
—CN  (IX)
R
F
—C(O)—CH═CH—NH—CH(Hal)—CH
2
—CN  (X)
 wherein R
F
, R
1
, Z and Hal are as defined above; and
(b) subjecting the reaction product of (a) to a ring closure reaction.
DETAILED DESCRIPTION OF THE INVENTION
Preferably, the symbols in the formulae (I)-(X) have the following meanings:
R
F
is preferably CH
2
F, CFCl
2
, CF
2
Cl, CF
3
or C
2
F
5
, particularly preferably CF
3
;
R
1
is preferably (C
1
-C
4
)-alkyl, such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, particularly preferably methyl or ethyl, very particularly preferably methyl;
Z is preferably O or NR
1
; and
halo is F, Cl, Br, or I, or preferably F or Cl.
The invention also relates to the use of 4-haloalkylnicotinonitriles as intermediates for the preparation of plant protection agents, in particular pesticides, such as insecticides.
The invention furthermore relates to a process for the preparation of 4-haloalkylnicotinamides having the formula (XI):
wherein R
F
is as defined above and wherein the 4-haloalkylnicotinonitrile having the formula (I):
obtained according to the above process is hydrolyzed.
A particular economic advantage compared with the known synthesis from the acid lies in the fact that by the process according to the invention no activated acid derivative, such as, for example, an acid chloride, is necessary and no reaction with ammonia has to be carried out.
The invention furthermore relates to compounds of the formulae (VIII), (IX) and (X) and their salts:
R
F
—C(O)—CH═CH—NH—CH═CH—CN  (VIII)
R
F
—C(O)—CH═CH—NH—CH(OR
2
)—CH
2
—CN  (IX)
R
F
—C(O)—CH═CH—NH—CH(Hal)—CH
2
—CN  (X)
wherein R
F
, Z and Hal have the meanings indicated above and R
2
is an alkyl group. The formulae (VIII), (XI) and (X) in this case include all stereoisomers of the compounds, such as (Z) and (E) isomers on the double bonds, e.g. the (Z,Z), (Z,E), (E,Z) and (E,E) isomers of the compound (VIII) and in each case the (Z) and (E) isomers of the compounds (IX) and (X). R
2
is preferably a linear or branched alkyl group having 1 to 6 carbon atoms, for example methyl, ethyl, n-propyl, iso-propyl, n-butyl or tert-butyl; methyl and ethyl are preferred, and methyl is particularly preferred.
The invention likewise relates to the use of compounds of the formula (VIII), (IX) and/or (X) as intermediates for the preparation of plant protection agents, in particular pesticides, such as insecticides.
4-Amino-1,1,1-trifluoro-3-buten-2-one (II), as a preferred starting material, is known and can be prepared, for example, as described in EP-A 0744400, by reacting an acid halide of the formula (XII):
CF
3
—COX  (XII)
wherein X is a halogen atom,
with a compound of the formula (XIII):
CH
2
═CHOR
3
  (XIII)
wherein R
3
is an alkyl group,
to give a compound of the formula (XIV):
R
F
—C(O)—CH═CH(OR)  (XIV)
from which, by reaction with ammonia, compound (II) is obtained.
Compounds of the formulae (III) to (VII) are known. They are commercially obtainable or can be prepared by known methods familiar to the person skilled in the art, such as are described, for example, in
J. Chem. Soc
. 1969, 406-408
; Bull. Soc. Chim. Fr
. 1948, 594 and
J. Org. Chem
. 29, 1964, 1800-1808.
R
3
is preferably a linear or branched alkyl group having 1 to 6, preferably 1 to 4, carbon atoms, for example methyl, ethyl, n-propyl, iso-propyl, n-butyl or tert-butyl; methyl and ethyl are preferred, and methyl is particularly preferred.
According to the invention, compound (II) is reacted in a condensation reaction with one or more compounds of the formulae (III) to (VII) to give compound (VIII), (IX) and/or (X).
The condensation of compound (II) with one or more compounds (III) to (VII) and the subsequent ring closure reaction are shown in the following scheme:
The condensation of (II) with (III)-(VII) is preferably carried out under reduced pressure (particularly preferably at a pressure in the range of from about 5 to about 150 mbar, very particularly preferably from about 10 to about 100 mbar). At the same time, the preferably low-boiling components are distilled off from the reaction mixture and in the process allow complete reaction of both starting materials. The vacuum is advantageously selected such that the boiling point of the eliminated compound R
1
ZH, such as CH
3
OH, EtOH, BuOH, is below, preferably about 50 to 10° C. below, the reaction temperature, and the boiling point of the solvent is above, preferably about 50 to 150° C. above, the reaction temperature. As the same time, the formation of by-products is largely suppressed, and the reaction rate increases.
The ratio of the two components (II) and (III) to (VII) in the reactions can vary to a large extent, depending on the compounds employed and further reaction conditions. Customarily, the molar ratio of the components (II):(III) to (VII) is about 1.0-1.2:1, preferably about 1.02-1.06:1. Depending on the compound employed, the reaction temperature and the other reaction conditions can be varied within wide limits. In general, the reaction temperature is in the range from about −20° C. to about +100° C., preferably from about 0° C. to about +30° C. and the reaction time is customarily from about 0.5 to about 12 h, preferably from about 1 to about 6 h. The reaction conditions also vary, depending on which compound of the formula (III) to (VII) is employed.
For the reaction with compounds of the formula (III)/(V), the reaction temperature is preferably from about −10 to about +75° C. For efficient conversion, the reaction is expediently carried out in the presence of a base. Suitable bases are, for example, alkali metal hydrides, such as NaH or KH; alkyllithium compounds, such as n-butyllithium or t-butyllithium; alkali metals, such as sodium or potassium; alkali metal hydroxides, such as NaOH or KOH; alkoxides, such as Na methoxide, Na ethoxide, K

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