Imidazolinone compounds, for instance, those described in U.S. Pat. Nos. 4,188,487; 4,798,619 and 5,334,576, are highly potent, broad spectrum, environmentally benign, herbicidal agents. In general, the herbicidal activity of the R-isomer is better than that of the racemic imidazolinone compound. A process to prepare chiral imidazolinones via the resolved optically active 2-amino-2,3-dimethylbutyramide enantiomers is described in U.S. Pat. No. 4,683,324. Said aminoamide enantiomers are prepared via the hydrolysis of their chiral 2-amino-2,4-dimethylbutyronitrile precursors and are difficult to isolate.
Therefore, it is an object of this invention to provide a stereospecific process to prepare chiral nicotinic, quinolinic or benzoic acid imidazolinone herbicidal agents directly from (R)2-amino-2,3-dimethylbutyronitrile without loss of optical purity and without the prior formation of (R)2-amino-2,3-dimethylbutyramide.
The present invention provides a stereospecific process to prepare a chiral compound of formula I 
wherein
X is N or CH; and
Y and Z are each independently H, C1-C4alkyl optionally substituted with one C1-C4alkoxy group or Y and Z may be taken together to form a group xe2x80x94CHxe2x95x90CHxe2x80x94CHxe2x95x90CHxe2x80x94
which process comprises the following steps:
a) reacting a compound of formula II 
wherein X, Y and Z are as described hereinabove with at least one molar equivalent of (R)2-amino-2,3-dimethylbutyronitrile in the presence of a non-polar, essentially water-free solvent, optionally in the presence of a tertiary amine, to form a first reaction mixture;
b) hydrolyzing said reaction mixture in aqueous acid to form an acidic second reaction mixture;
c) reacting said second reaction mixture with an excess of an aqueous base at a temperature of about 20xc2x0-85xc2x0 to form a basic third reaction mixture;
d) separating said third reaction mixture to obtain an aqueous phase; and
e) acidifying said aqueous phase to obtain the desired chiral formula I imidazolinone compound.
Chiral imidazolinone compounds having the R configuration demonstrate about a 2-fold increase in herbicidal activity over the corresponding racemic mixture. Heretofore, (R)imidazolinone compounds were prepared from (R)2-amino-2,3-dimethylbutyramide due to the instability of the (R)2-amino-2,3-dimethylbutyronitrile compound. However, isolation of said (R)aminoamide is difficult. Surprisingly, it has now been found that chiral imidazolinone herbicides may be prepared directly from (R)2-amino-2,3-dimethylbutyronitrile in the presence of a non-polar essentially water-free solvent with substantially complete retention of enantiomeric purity from the (R)aminonitrile starting material to the final chiral imidazolinone herbicidal product. Advantageously, the process of the invention eliminates the need for the prior formation of (R)2amino-2,3-dimethylbutyramide.
In accordance with the process of the invention, a formula II anhydride is reacted with at least one molar equivalent of (R)2-amino-2,3-dimethylbutyronitrile in the presence of a non-polar, essentially water-free solvent, optionally in the presence of a tertiary amine, to form a first reaction mixture; said reaction mixture is hydrolyzed with aqueous acid to form an acidic second reaction mixture; said second reaction mixture is treated with an excess of a base at a temperature of about 20xc2x0-90xc2x0 C. to form a basic third reaction mixture; said third reaction mixture is separated to obtain an aqueous phase; and the aqueous phase is acidified to obtain the desired chiral formula I imidazolinone herbicide. The process is illustrated in flow diagram I. In the specification and claims, an asterisk designates the assymetric carbon upon which the (R) configuration is conferred. 
Solvents suitable for use in the process of the invention are non-polar essentially water-free solvents such as aromatic hydrocarbons (e.g. toluene, benzene, xylene, naphthalene and the like, preferably toluene), halogenated aromatic hdrocarbons (e.g. chlorobenzene, dichlorobenzenes and the like), hydrocarbons (e.g. pentanes, hexanes and the like), halogenated hydrocarbons (e.g. chloroform, methylene chloride, dichlorethane, and the like, esters (e.g. ethyl acetate, methyl propionate and the like), ethers (e.g. diethyl ether, tetrahydrofuran, dioxane and the like) or any of the conventional, preferably water immiscible, organic non-polar solvents.
Preferred non-polar solvents suitable for the process of the invention are aromatic hydrocarbons, particularly toluene.
Tertiary amines suitable for use in the first step of the inventive process are pyridine, 4-cyanopyridine, 4-picoline, 2-picoline, mixed picolines, tri(C1-C4)alkylamine, quinoline or any of the conventional organic tertiary amines, preferably 4-picoline. The amine may be present in amounts ranging from catalytic to excess amounts such as 10 mole % to 4.0 molar excess.
Acids suitable for use in the process of the invention include strong mineral acids such as HCl or H2SO4, preferably H2SO4.
Bases suitable for use in the inventive process include alkali metal hydroxides or alkoxides, preferably hydroxides such as NaOH or KOH, preferably NaOH. These may be present at about 2 to 20 molar-equivalents, preferably about 2 to 8 molar-equivalents.
It is also intended that the process of the invention embraces the use of (S)-2,3-dimethylbutyronitrile to prepare the corresponding (S)-imidazolinone herbicidal product.
In actual practice, a mixture of the formula II anhydride in a non-polar, essentially water-free solvent, preferably an aromatic hydrocarbon, more preferably toluene, is treated with a 10% to 60% solution of (R)2-amino-2,3-dimethylbutyronitrile in a non-polar, essentially water-free solvent, preferably an aromatic hydrocarbon, more preferably toluene, optionally in the presence of 10 mol % to 4.0 molar excess, preferably about 10 mol % to 1.0 molar equivalent of 4-picoline, at a temperature of about 5xc2x0 to 45xc2x0 C., preferably about 5xc2x0 C. to 30xc2x0 C., to form a first reaction mixture; said mixture is treated with a strong mineral acid, preferably H2SO4, and water at temperatures of about 5xc2x0 to 80xc2x0 C., preferably about 20xc2x0 C. to 60xc2x0 C. to form an acidic second reaction mixture; said second mixture is treated with an excess, (about 2 to 20 moles per mole of acid used in the previous hydrolysis step) of an aqueous alkali metal hydroxide or alkoxide, preferably an alkali metal hydroxide, more preferably NaOH or KOH, of 10% or greater concentration on a weight basis at temperatures of about 15xc2x0 C. to 90xc2x0 C., preferably 20xc2x0 C. to 85xc2x0 C., to form a basic third reaction mixture; said third reaction mixture is separated to obtain an aqueous phase; and said aqueous phase is acidified with a strong mineral acid such as HCl, HBr or H2SO4, preferably H2SO4, to a pH of about 2 to 4 to obtain the desired chiral formula I imidazolinone product. The product may be isolated using conventional procedures such as filtration, extraction with a suitable solvent, chromatographic separation and the like, preferably filtration or extraction.
In order to facilitate a further understanding of the invention, the following examples are presented primarily for the purpose of illustrating certain more specific details thereof. The invention is not to be deemed limited thereby except as defined in the claims. Unless otherwise noted, all parts are by weight. NMR designates nuclear magnetic resonance. HPLC designates high performance liquid chromatography.