Abstract:
The invention relates to a process for the preparation of synthetic pyrethroid insecticides. The process involves coupling of carboxylic acid (IV) with an alcohol (V) in the presence of a catalyst
wherein R1, R2, R3 and Ar are defined in the specification.
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Notices, Deadlines & Correspondence
SYNGENTA CROP PROTECTION, MONTHEY SA, ROUTE DE I'LLE AU BOIS, 1870 MONTHEY, SWITZERLAND
Specification
PROCESSES FOR THE PREPARATION OF ESTERS
The present invention relates to a process for the preparation of certain pyrethroid compounds useful as insecticides, as well as a process for the preparation of intermediates useful in the synthesis of such compounds.
Synthetic pyrethroid insecticides of the formula (I) are disclosed in GB2000764
(Formula Removed)
wherein
one of R1 and R2 represents a group of formula: W~(CF2)m~ where W represents an atom of hydrogen, fluorine or chlorine and m has the value one or two, and the other of Rl and R2 represents an atom of fluorine, chlorine or bromine, and R3 represents an atom of hydrogen or the cyano or ethynyl group.
Synthetic pyrethroid insecticides of the formula (II) are disclosed in US4405640
(Formula Removed)
wherein
Rl and R2 are each selected from methyl, halomethyl, and halo; X is oxygen, sulphur, sulphonyl or a group NR4 where R4 represents hydrogen, lower alky] or lower carboxylic acyl; R3 is lower alkyl, lower alkenyl or benzyl; m has the value zero to one, and n has a value from one to four.
The present invention seeks to provide processes for the preparation of these and other pyrethroids.
It has now surprisingly been found that these compounds may advantageously obtained by coupling the corresponding alcohol and carboxylic acid in the presence of a catalyst, as described below.
The present invention provides a process for the preparation of compounds of formula (III)
(Formula Removed)
wherein
Rl is hydrogen, alkyl, haloalkyl, or halogen;
R2 is hydrogen, alkyl, haloalkyl, or halogen;
R3 is hydrogen, halogen, hydroxyl, nitro, cyano, optionally substituted alkyl, optionally
substituted alkenyl, or optionally substituted alkynyl;
Ar is an optionally substituted aryl groupcomprising reacting a carboxylic acid of formula (IV)
(Formula Removed)
with an alcohol of the formula (V)
(Formula Removed)
in the presence of a catalyst selected from zirconium containing catalysts, hafnium containing catalysts, iron containing catalysts, cobalt containing catalysts, tin containing catalysts, titanium containing catalysts, ammonium salt catalysts and boronic acid containing catalysts.
Preferably, Rl and R2 are independently selected from hydrogen, halogen, C1-C4 alkyl and C1-C4 haloalkyl.
Preferably, R3 is selected from hydrogen, halogen, hydroxyl, nitro, cyano, C1-C4 alkyl and C1-C4 haloalkyl, more preferably hydrogen, cyano or C3-C4 alkynyl.
Preferably Ar is phenyl substituted with one or more groups selected from hydrogen, halogen, hydroxyl, nitro, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and phenoxy.
Halo is fluoro, chloro or bromo.
Each alkyl moiety is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl or neo-pentyl. Preferred alkyl groups have from 1 to 6 carbon atoms.
Haloalkyl refers to an alkyl moiety as defined above wherein at least one hydrogen atom is substituted for a halo atom.
Aryl refers to a phenyl or napthyl group.
Heteroaryl refers to a mono- or bicyclic ring system wherein each ring comprises from 5 to 7 ring member atoms, and from 1 to 3 heteroatoms independently selected from O, N and S. Examples of heteroaryl groups are pyridine, pyrrole, furan, pyrazole, imidazole and oxazole.
Alkenyl refers to a straight or branched group consisting of carbon and hydrogen atoms comprising at least one carbon-carbon double bond. Examples are ethenyl, prop-1-enyl, prop-2-enyl, but-1-enyl, but-2-enyl and but-3-enyl. Both cis- and trans- groups are contemplated. Preferred alkenyl groups have from 2 to 6 carbon atoms.
AJkynyl refers to a straight or branched group consisting of carbon and hydrogen atoms comprising at least one carbon-carbon triple bond. Examples are ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl and but-3-ynyI. Preferred alkynyl groups have from 2 to 6 carbon atoms.
Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
When present, each optional substituent on aryl or on heteroaryl is, independently, preferably selected from alkyl, alkenyl, alykynyl, alkoxyl, alkenyloxy, aryloxy, thioalkyl, amino, alkylamino, dialkylamino, aralkyl, acetamido, n-alkyl acetamido, alkylsufonyl, halo, hydroxyl, cyano and nitro. From one to the maximum possible number of substituents may be present.
Preferably, one of Rl and R2 is halo, and the other is haloalkyl. More preferably, one of Rl and R2 is chloro, and the other is haloalkyl, e.g. halo-Cl-C4-alkyl. More preferably, one of Rl and R2 is halo, and the other is trifluoromethyl. Most preferably, one of Rl and R2 is chloro, and the other is trifluoromethyl.
Preferably, the substituents on the cyclopropane ring are in the cis- stereochemistry. That is, the compound of formula (III) has the stereochemistry (Ilia)
(Formula Removed)
Preferably, the compound of formula (III) has the formula (1Kb)
(Formula Removed)
Very preferably, the compound of formula (III) has the formula (IIIc)
(Formula Removed)
In a preferred embodiment, Ar is an optionally substituted phenyl group.
In a highly preferred embodiment, Ar is a phenoxyphenyl group. More preferably, Ar is a 3-phenoxyphenyl group. In this embodiment, it is preferred that R3 is cyano or ethynyl. It is more preferred that R3 is cyano.
For example,
One of Rl and R2 is halo, and the other is ha!o-Cl-C4-alkyl;
R3 is cyano or ethynyl;
Ar is is a phenoxyphenyl group.
Very highly preferably, the compound of formula (III) has the formula (Hid)
(Formula Removed)
In an alternative preferred embodiment, AT is a group of the formula (VI)
(Formula Removed)
wherein R4 is selected from alky], alkenyl, alykynyl, alkoxyl, alkenyloxy, aryloxy, thioalkyl, amino, alkylamino, dialkylamino, aralkyl, acetamido, n-alkyl acetamido, alkylsufonyl, halo, hydroxyl, cyano and nitro. Preferably, R4 is alkyl of 1 to 4 carbon atoms, alkenyl of three to five carbon atoms, methoxy, ethoxy, allyloxy, ethylthio, ethanesulphonyl, benzyl, dimethylamino, ethylamino, acetamido or n-methylacetamido. Very preferably, R4 is methyl. Preferably, R4 is in the 4-position.
In this embodiment, it is preferred that R3 is hydrogen,
For example,
One of Rl and R2 is halo, and the other is halo-Cl-C4-alkyl;
R3 is hydrogen;
Ar is a group of the formula (VI)
(Formula Removed)
R4 is alkyl of 1 to 4 carbon atoms, alkenyl of three to five carbon atoms, methoxy, ethoxy, allyloxy, ethylthio, ethanesulphonyl, benzyl, dimethylamino, ethylamino, acetamido or n-methylacetamido.
Very highly preferably, the compound of formula (III) has the formula (Ille)
(Formula Removed)
According to a very highly preferred embodiment, the invention provides a process for the preparation of tefluthrin (VII)
(Formula Removed)
comprising reacting a carboxylic acid of formula (VIII) with an alcohol of formula (IX)
(Formula Removed)
in the presence of a catalyst selected from zirconium containing catalysts, hafnium containing catalysts, iron containing catalysts, cobalt containing catalysts, tin containing catalysts, titanium containing catalysts, ammonium salt catalysts and boronic acid containing catalysts.
According to an alternative very highly preferred embodiment, the invention provides a process for the preparation of lambda cyhalothrin (X)
(Formula Removed)
comprising reacting a carboxylic acid of formula (VIII) with an alcohol of formula (XI)
(Formula Removed)
in the presence of a catalyst selected from zirconium containing catalysts, hafnium containing catalysts, iron containing catalysts, cobalt containing catalysts, tin containing catalysts, titanium containing catalysts, ammonium salt catalysts and boronic acid containing catalysts.
Compound (XI) may be generated in situ.
The present invention also relates to a process substantially as described herein with reference to the examples.
The present invention also relates to a compound obtainable by the process described herein. The present invention also relates to a compound obtained by the processes described herein.
Enantiomers
The processes of the invention may be used to prepare enantiomerically enriched or pure forms of the compounds. In a preferred embodiment, the invention provides a process for the preparation of gamma-cyhalothrin (S)-a-cyano-3-phenoxybenzyl (Z) - (lR,3R)-3-(2