Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Reexamination Certificate
1993-09-13
2001-05-22
Raymond, Richard L. (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
Reexamination Certificate
active
06235904
ABSTRACT:
The present invention relates to novel 2-amino-(fluoroalkoxy)pyrimidines of the formula I
where R
R
1
is hydrogen, C
1
-C
4
-alkyl, C
3
-C
4
-alkenyl or C
3
-C
4
-alkynyl,
R
2
is hydrogen, halogen or C
1
-C
4
-haloalkyl, or else trifluoromethoxy or chlorodifluoromethoxy,
R
3
is hydrogen, halogen or C
1
-C
4
-haloalkyl and
n is 0 or 1.
The present invention also relates to a process for preparing the pyrimidines I by reacting fluoroalkoxy-2-halopyrimidines with amines.
The pyrimidines I are valuable intermediates for organic syntheses, especially for preparing crop protection agents.
There are many indications in the literature that, because of similar electronic properties, fluoroalkyl and fluoroalkoxy groups are equivalent to halogens. Measurements of pKa (Proc. Nat. Acad. Sci. USA 134 (1960) 1207, J. Am. Chem. Soc. 83 (1961) 4860) demonstrate that, for example, fluoroalkoxy groups are inductive electron attractors but, conversely, also act as electron donors because of the possibility of resonance. Taking all the effects into account, the trifluoromethoxy group is in fact more strongly deactivating than the halogens, so that the term “superhalogens” has been used (J. Am. Chem. Soc. 83 (1961) 4860). This applies in the same way to their replaceability by nucleophiles. For example, Chemical Abstracts 87, 53396 demonstrates that two haloalkyl groups in 2,4-bis (trichloromethyl)-6-trifluoromethyl-s-triazine are replaced on stirring with basic amines in benzene. The ability of trifluoromethoxy to act as leaving group is also used, for example, in sugar chemistry (CA. 105, 115325; 107, 96978).
Thus, with this background, the existing processes for preparing 2-amino(fluoroalkoxy)pyrimidines are very elaborate and timeconsuming. For example, it is necessary first to convert an appropriately substituted 2-halopyrimidine with methyl mercaptan, which is toxic, into the 2-methylthiopyrimidine, which is then oxidized to the 2-methylsulfonyl derivative which is subjected to nucleophilic displacement with an amine (U.S. Pat. No. 4,542,216).
We have found that the novel 2-amino(fluoroalkoxy)pyrimidines of the formula I
where R
1
, R
2
, R
3
and n have the abovementioned meanings, are obtained advantageously by reacting 2-halopyrimidines of the formula II
where Hal is fluorine, chlorine, bromine or iodine, and R
2
, R
3
and n have the abovementioned meanings, with an amine of the formula III
H—NH—R
1
III
where R
1
has the abovementioned meaning.
The reaction of 2,4-difluoro-6-trifluoromethoxypyrimidine and ammonia is shown in the following diagram:
The process provides novel 2-amino(fluoroalkoxy)pyrimidines in high yields and purity in a straight-forward and economic manner. Against expectation, fluoroalkoxy groups are not replaced under the reaction conditions. In view of the prior art, all these advantageous properties are surprising.
Preferred final products I and, accordingly, preferred starting materials II are those in whose formulae R
1
is hydrogen, C
1
-C
4
-alkyl such as methyl, ethyl, n-propyl, i-propyl, n-butyl, sec.-butyl, i-butyl or tert.-butyl, C
3
-C
4
-alkenyl such as 2-propenyl, 2-methylethenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl or 2-methyl-2-propenyl, C
3
-C
4
-alkynyl such as propargyl, 2-butynyl, 3-butynyl or 1-methyl-2-propynyl, R
2
and R
3
are, independently of one another, hydrogen, fluorine, chlorine, bromine, trichloromethyl, dichlorofluoromethyl, chlorodifluoromethyl, trifluoromethyl, 1,1-dichloro-2,2,2-trifluoroethyl, 1,1,2,2,2-pentafluoroethyl or 1,1,2,2,2-pentachloroethyl, and, furthermore, R
2
is trifluoromethoxy or chlorodifluoromethoxy, and n is 0 or 1.
Among the amines which can be employed, the following may be mentioned: ammonia, methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, isobutylamine, sec.-butylamine, tert.-butylamine, 2-propenylamine, 2-methylethenylamine, 2-butenylamine, 3-butenylamine, 1-methyl-2-propenylamine, 2-methyl-2-propenylamine, propargylamine, 2-butynylamine, 3-butynylamine and 1-methyl-2-propynylamine.
The 2-halopyrimidines II can be reacted with the amines III in an aprotic polar solvent at from −80 to 40° C., either employing the amine III in excess relative to II or using an additional organic base.
The reaction of the 2-halopyrimidine II with the amine III can be carried out in the absence or, advantageously, in the presence of a solvent. Particularly suitable solvents are the following:
Ethers such as methyl tert.-butyl ether, diethyl ether, ethyl propyl ether, n-butyl ethyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, diiso-propyl ether, cyclohexyl methyl ether, tetrahydrofuran, 1,2-dimethoxyethane, diethylene glycol dimethyl ether and anisole, esters such as ethyl acetate, n-butyl acetate and isobutyl acetate, and chlorohydrocarbons such as methylene chloride, 1,1,2,2-tetrachloroethane, 1,1-dichloroethylene, 1,2-dichloroethane, chlorobenzene, 1,2-dichlorobenzene and 1-chloronaphthalene, and mixtures of these solvents.
The solvent is expediently used in an amount of from 100 to 2000% by weight, preferably 400 to 1200% by weight, based on the starting material II.
It is advantageous to add from 1.8 to 2.5, in particular 1.95 to 2.2, mole equivalents of the amine III based on the starting material II over the course of 0.5 to 2 hours to the starting material II in one of the abovementioned solvents at from −80 to 40° C., preferably −70 to 25° C., to stir until the reaction is complete (after about 3 hours) and then to allow to warm to 25° C. for the working up.
If only approximately the stoichiometric amount of the amine III is employed, it is expedient to use an additional organic base in order to trap the hydrogen halide which is generated. Suitable for this are the customary organic bases such as trimethylamine, triethylamine, ethyldiisopropylamine, triisopropylamine, N,N-dimethylaniline, N,N-dimethylcyclohexylamine, N-methylpyrrolidine, pyridine, quinoline, &agr;-, &bgr;- or &ggr;-picoline, 2,4- or 2,6-lutidine and triethylenediamine. It generally suffices to add from 0.9 to 1.1 equivalents of the base relative to starting material II.
The reaction can be carried out under atmospheric or superatmospheric pressure, continuously or batchwise.
The working up can be carried out in a conventional manner, eg. the reaction mixture is extracted with water to remove the salts, and the organic phase is dried and purified, eg. by chromatography. However, it is also possible to concentrate the organic phase directly and to stir the residue with a solvent.
With a view to the further processing thereof to herbicidal compounds, eg. sulfonylurea derivatives, the following pyrimidines of the formula I are particularly preferred:
2-amino-4-chloro-6-trifluoromethoxypyrimidine,
2-amino-4-fluoro-6-trifluoromethoxypyrimidine,
2-amino-4-chloro-6-chlorodifluoromethoxypyrimidine,
2-amino-4-fluoro-6-chlorodifluoromethoxypyrimidine,
2-amino-4,6-bis(trifluoromethoxy)pyrimidine,
2-amino-4,6-bis(chlorodifluoromethoxy)pyrimidine,
2-amino-4-trifluoromethoxy-6-trifluoromethylpyrimidine,
2-amino-4-chlorodifluoromethoxy-6-trifluoromethylpyrimidine,
2-amino-4,5-dichloro-6-trifluoromethoxypyrimidine,
2-amino-4-chloro-6-trifluoromethoxy-5-trifluoromethylpyrimidine,
2-methylamino-4-chloro-6-trifluoromethoxypyrimidine,
2-methylamino-4-fluoro-6-trifluoromethoxypyrimidine,
2-methylamino-4-chloro-6-chlorodifluoromethoxypyrimidine,
2-methylamino-4-fluoro-6-chlorodifluoromethoxypyrimidine,
2-methylamino-4,6-bis(trifluoromethoxy)pyrimidine,
2-methylamino-4,6-bis(chlorodifluoromethoxy)pyrimidine,
2-methylamino-4-trifluoromethoxy-6-trifluoromethylpyrimidine,
2-methylamino-4-chlorodifluoromethoxy-6-trifluoromethylpyrimidine,
2-methylamino-4,5-dichloro-6-trifluoromethoxypyrimidine,
2-methylamino-4-chloro-6-trifluoromethoxy-5-trifluoromethylpyrimidine,
2-allylamino-4-chloro-6-trifluoromethoxypyrimidine,
2-allylamino-4-fluoro-6-trifluoromethoxypyrimidine,
2-allylamino-4-chloro-6-chlorodifluoromethoxypyrimidine,
2-allylamino-4-fluoro-6-chlorodifluoromethoxypyrimidine,
2-allylamino-4,6-bis(trif
BASF - Aktiengesellschaft
Keil & Weinkauf
Raymond Richard L.
LandOfFree
2-amino (fluoroalkoxy) pyrimidines and the preparation thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 2-amino (fluoroalkoxy) pyrimidines and the preparation thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 2-amino (fluoroalkoxy) pyrimidines and the preparation thereof will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2485113