Organic compounds -- part of the class 532-570 series – Organic compounds – Phosphorus esters
Reexamination Certificate
2000-02-17
2002-03-19
Powers, Fiona T. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Phosphorus esters
C558S179000, C558S346000, C558S386000, C562S011000, C562S024000
Reexamination Certificate
active
06359162
ABSTRACT:
The invention relates to the technical field of the processes for preparing biologically active compounds and precursors thereof, preferably of crop protection agents, in particular the herbicide glufosinate, also known as phosphinothricin.
Glufosinate (see formula (Ia)) is the common name for the active compound (D,L)-2-amino-4-[hydroxy(methyl)phosphinyl]butanoic acid, which is commercially available as monoammonium salt and is used as foliar herbicide (see DE-A-2717440, U.S. Pat. No. 4,168,963).
The herbicide can be employed for the non-selective control of weeds in fruit growing and viticulture, in plantation crops, in vegetable growing prior to sowing or transplanting, prior to direct sowing of maize or soya beans, and also on uncultivated land, such as roadsides, industrial terrain and railroad tracks (cf. Z. PflKrankh.PflSchutz, Special Edition IX, 431-440, 1981). Also known is the selective use for controlling weeds in crops of useful plants, such as, inter alia, maize and rapeseed, which have been made resistant by gene technology (cf. EP-A-0242246).
A large number of processes for preparing glufosinate have been disclosed. According to the variant described in EP-A-0011245 (U.S. Pat. No. 4,521,348), phosphorus-containing cyanohydrin derivatives of the formula
in which R is a hydrocarbon radical such as alkyl, haloalkyl, cycloalkyl, phenyl or benzyl, with or without substitution, R′ is hydrogen, alkyl, phenyl or benzyl and R″ is hydrogen, acyl, trialkylsilyl or alkylsulfonylalkyl, can be converted into aminonitriles, which in turn can be hydrolyzed to give glufosinate. According to EP-A-0011245, the preparation of the cyanohydrin derivatives is carried out by reaction of a monoalkyl methanephosphonate and an acroleincyanohydrin derivative of the formula
in which R′ and R″ are as defined above. The described process has the disadvantage that the phoshorus-containing derivative and its precursors have to be provided in the form of esters, whereas in the desired product glufosinate (Ia), the (hydroxy)(methyl)phosphinyl radical is present in hydrolyzed form.
It is an object of the present invention to provide an alternative process to the process described above, said process allowing the number of ester precursors to be reduced and being suitable for preparing glufosinate and related compounds.
The invention provides a process for preparing compounds of the formula (I),
in which R* is hydrogen or (C
1
-C
4
)-alkyl, preferably H or methyl, or salts thereof with acids or bases, which comprises
a) (Step 1)
reacting a trivalent methylphosphorus compound of the formula (II) with an unsaturated derivative of the formula (III), if appropriate in the presence of a condensing agent or activator and, if appropriate, alcohols, to give an adduct (IV),
Step 1:
where in the formulae
R
1
and R
2
independently of one another are halogen, such as, for example, fluorine, chlorine, bromine or iodine, (C
1
-C
18
)alkoxy with or without substitution, benzyloxy or phenoxy, which may also be substituted, or one of the radicals R
1
and R
2
is hydroxyl, and
R* is as defined in formula (I),
b) (Step 2)
the adduct (IV) is, if appropriate after hydrolytic ring opening to aldehydes (R*=H) or ketones (R*=alkyl) of the formula (IV′) or salt thereof,
in which Z is OH, R
1
or R
2
, reacted under the conditions of a Strecker synthesis with ammonia/ammonium chloride and sodium cyanide or alternatively with mixtures of ammonia and hydrocyanic acid or with ammonia and a salt of hydrocyanic acid, such as, for example, ammonium cyanide or potassium cyanide, if appropriate in the presence of ammonium chloride, to give the &agr;-aminonitriles of the formula (V) or a salt thereof,
Step 2:
where in the formulae (IV′) and (V) the radical R* is as defined in formula (I) and Z is as defined in formula (IV′) or is OH, and
c) (Step 3)
the compound of the formula (V) is hydrolyzed under acidic or basic conditions to give the compound of the formula (I) or the salt thereof.
In the abovementioned formulae and in the formulae used hereinbelow, the radicals alkyl, alkoxy, haloalkyl, haloalkoxy, alkylamino and alkylthio, and also the corresponding unsaturated radicals and/or radicals which are substituted in the carbon skeleton, may in each case be straight chain or branched. Unless specifically indicated, preference for these radicals is given to the lower carbon skeletons, for example those having 1 to 4 carbon atoms and, in the case of unsaturated groups, those having 2 to 4 carbon atoms. Alkyl radicals, also in the composed meanings such as alkoxy, haloalkyl, etc., are, for example, methyl, ethyl, n- or i-propyl, n-, i-, t- or 2-butyl, pentyls, hexyls, such as n-hexyl, i-hexyl and 1,3-dimethylbutyl, heptyls, such as n-heptyl, 1-methylhexyl and 1,4-dimethylpentyl; cycloalkyl is a carbocyclic saturated ring system, for example having 3 to 8 ring atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.; alkenyl, alkynyl and cycloalkenyl radicals have the meaning of the possible unsaturated radicals which correspond to the alkyl or cycloalkyl radicals; alkenyl is, for example, allyl, 1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1-yl, methylbut-3-en-1-yl and 1-methylbut-2-en-1-yl; cycloalkenyl is, for example, cyclopentenyl or cyclohexenyl; alkynyl is, for example, propargyl, but-2-yn-1-yl, but-3-yn-1-yl or 1-methylbut-3-yn-1-yl. Alkenyl in the form “(C
3
-C
4
)alkenyl” or “(C
3
-C
6
)-alkenyl” is preferably an alkenyl radical having 3 to 4 and 3 to 6 carbon atoms, respectively, where the double bond is not adjacent to the carbon atom which is attached to the rest of the molecule moiety of the compound (I) (“yl” position). This applies correspondingly to (C
3
-C
4
)-alkynyl, etc.
Halogen is, for example, fluorine, chlorine, bromine or iodine. Haloalkyl, -alkenyl and -alkynyl are alkyl, alkenyl and alkynyl, respectively, which are partially or fully substituted by halogen, preferably by fluorine, chlorine and/or bromine, in particular by fluorine or chlorine, for example CF
3
, CHF
2
, CH
2
F, CF
3
CF
2
, CH
2
FCHCl
2
, CCl
3
, CHCl
2
, CH
2
CH
2
Cl; haloalkoxy is, for example, OCF
3
, OCHF
2
, OCH
2
F, CF
3
CF
2
O, OCH
2
CF
3
and OCH
2
CH
2
Cl; this applies correspondingly to haloalkenyl and to other halogen-substituted radicals.
If substitutions are defined by “one or more radicals selected from a group of radicals”, this includes both the substitution by one or more identical radicals and mono- or polysubstitution by different radicals.
Substituted radicals, such as substituted hydrocarbon radicals, for example substituted alkyl, alkenyl, alkynyl, aryl, phenyl., and benzyl, or substituted heterocyclyl, are, for example, a substituted radical derived from the unsubstituted parent radical, where the substituents are, for example, one or more, preferably 1, 2 or 3, radicals selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, hydroxyl, amino, nitro, cyano, azido, alkoxycarbonyl, alkylcarbonyl, formyl, carbamoyl, mono- and dialkyl-aminocarbonyl, substituted amino such as acylamino, mono- or dialkyl-amino, and alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl and, in the case of cyclic radicals, also alkyl and haloalkyl, and unsaturated aliphatic radicals corresponding to the abovementioned saturated hydrocarbon-containing radicals, such as alkenyl, alkynyl, alkenyloxy, alkynyloxy etc. Preferred radicals having carbon atoms are those having 1 to 4 carbon atoms, in particular 1 or 2 carbon atoms. Preferred substituents are usually those from the group consisting of halogen, for example fluorine and chlorine, (C
1
-C
4
)alkyl, preferably methyl or ethyl, (C
1
-C
4
)-haloalkyl, preferably trifluoromethyl, (C
1
-C
4
)-alkoxy, preferably methoxy or ethoxy, (C
1
-C
4
)-haloalkoxy, nitro and cyano. Particular preference is given to the substituents methyl, methoxy and chlorine.
Phenyl with or without substitution is preferably phenyl which is unsubstitute
Frommer & Lawrence & Haug LLP
Hoechst Schering AgrEvo GmbH
Powers Fiona T.
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