United States Patent (19) 11) Patent Number: 4,636,562 Davis (45) Date of Patent: Jan
Total Page：16
File Type：pdf, Size：1020Kb
United States Patent (19) 11) Patent Number: 4,636,562 Davis (45) Date of Patent: Jan. 13, 1987 54) PROCESS FOR PREPARING 6-HALO-2-CHLOROQUINOXALINE FOREIGN PATENT DOCUMENTS (75) Inventor: Richard F. Davis, Newark, Del. 48973 3/1982 Japan. (73) Assignee: E. I. Du Pont de Nemours and OTHER PUBLICATIONS Company, Wilmington, Del. Burton et al., J. Chem. Soc. C)1968, pp. 1274-1280. BASF, Chem. Abs, 60,2987f (1963). 21) Appl. No.: 667,467 Cheeseman et al., "Condensed Pyrazines', vol. 35, pp. 22 Filed: Nov. 1, 1984 162, 168 (Wiley, NY) 1979. A. S. Elina et al., Zh. Obsch. Khim, 33, 1544 (1963). Related U.S. Application Data R. E. Lutz et al., J. Amer. Chem. Soc., 68, 1322 (1946). 63) Continuation-in-part of Ser. No. 375,977, May 7, 1982, Primary Examiner-Mark L. Berch abandoned. (57) ABSTRACT (51) Int. Cl'....................... C07D 241/44; CO7B 1/00 A process for the preparation of 2-chloro-6-haloquinox (52) U.S. C. .................................... 544/354; 544/356; aline compounds from the corresponding 4-halo-2- 564/133 nitroaniline utilizing four reaction steps with generally (58) Field of Search ................................ 544/354, 356 compatible solvents and reagents with volatile by-pro (56) References Cited ducts to minimize the isolation and purification of inter U.S. PATENT DOCUMENTS mediates has been developed. 3,252,941 11/1966 Chang et al. ........................ 544/354 10 Claims, No Drawings 4,636,562 1. 2 reported, and the reduction of compounds with halogen PROCESS FOR PREPARNG substitution at the six (6)-position was not considered. 6-HALO-2-CHLOROQUINOXALINE Amadet al. (Tetrahedron 20, 1107 (1964) reports the use of sodium dithionite to reduce 6-chloro-3-cyano-2- RELATED APPLICATION hydroxyquinoxaline-4-oxide. The reaction results in the This application is a continuation-in-part application loss of the nitrile group (strongly electron withdrawing) of Ser. No. 375,977, filed May 7, 1982, abandoned. with simultaneous formation of 2-hydroxyquinoxaline. TECHNICAL FIELD Katritzky and Monro J. Chem. Soc., 1958, 1263) describe the reduction of substituted pyridine N-oxides This invention relates to a process for the preparation 10 using hydrogen and palladium/carbon catalyst. The of 6-halo-2-chloroquinoxaline, an important starting substituted fused-ring quinoline 4-oxides are however material for the synthesis of quinoxalinyloxy ether her reported to be resistant to such reduction. bicides. Taylor and Jefford Chem. and Ind., 1963, 1559) dis BACKGROUND OF THE INVENTION 15 close the reduction of quinoxaline-4-oxides with amino The 6-halo-2-chloroquinoxaline compounds are start substitution to block the reactive three (3)-position ing reagents for the preparation of quinoxalinyloxy using hydrogen and Raney nickel catalyst. The reaction ether compounds European Patent Office Application is run in a mixture of ethanol and methylamine, and the No. 81302801.6, published Dec. 30, 1981) which have effect of halogen substitution in the aromatic ring is not utility as herbicides, particularly for the control of grass 20 considered. weeds in paddy rice, soybeans, cotton, potatoes, etc. Crowther et al. J. Chem. Soc., 1949, 1260 discloses Rice is the second largest food crop with over 320 mil the use of phosphorus oxychloride for the conversion of lion metric tons annual production worldwide J. R. 2-hydroxyquinoxalines to 2-chloroquinoxalines. The Harlan, 235 Sci. Amer., 88 (1976). Undesired compet phosphorous compound by-products are removed by ing vegetation, such as the extremely prevalent bar 25 reacting with ice-water to decompose them to an aque nyardgrass (Echinochloa crusgali) and closely related ous phosphoric acid solution. species can reduce rice yield by 25% if allowed to com Given the anticipated importance of quinoxalinyloxy pete all season at an infestation of only one plant per ether herbicides, what is needed is an economical pro square foot Agricultural Age, May 1977, page 11). cess for producing 6-halo-2-chloroquinoxaline com Soybeans, with over 60 million metric tons annual pro 30 duction worldwide Sci. Amer, 235, 88 (1976) is an pounds at high yield without contamination by isomeric extremely valuable crop which must often compete impurities. with such grassweeds as crabgrass, barnyardgrass, and SUMMARY OF THE INVENTION wild oats. By inhibiting the growth or killing such unde sired vegetation, significant improvements in agricul 35 By specifically designing the reaction steps of the tural efficiency are realized. - instant process invention to utilize compatible solvents Toman et al. Coll. Czech. Chem. Commun., 43,2179 and reagents with volatile by-products, it has been (1978) disclose a procedure for reaction of 4-chloro-2- found possible to produce 2-chloro-6-haloquinoxaline nitroaniline with diketene in refluxing chlorobenzene at from 4-halo-2-nitroaniline in good yield, with minimum 132 C. The use of such high temperatures results in isolation, and no purification, of process intermediates. competing decomposition and polymerization reactions By insuring maximum interconnection of the process of diketene and a lower yield. Toman et al. also disclose steps, handling losses are minimized resulting in high a procedure for reaction of 4-chloro-2- overall yield. The instant invention also avoids the pro nitroacetoacetanilide with base in aqueous ethanol to duction of 7-halo isomer compounds. Specifically, one produce the 2-hydroxyquinoxaline-4-oxide. The use of 45 aspect of this invention involves the preparation of ethanol-water solvent is costly, precludes direct contin 2-chloro-6-haloquinoxaline, wherein the halo-substitu ued use of the reaction product in subsequent process ent can be fluorine, chlorine, or bromine, by the process ing steps and results in waste streams containing flam comprising (a) contacting, and reacting 4-halo-2- mable materials. nitroaniline with diketene to produce 4-halo-2- U.S. Pat. No. 3,708,580 discloses the reaction of sub 50 stituted 2-mitroanilines with diketene in a solution of nitroacetoacetanilide followed by removing solvent glacial acetic acid and mercuric acetate. Continued therefrom to enable subsequent processing; (b) contact processing of the 2-nitroacetoacetanilide requires addi ing and reacting 4-halo-2-nitroacetoacetanilide with tional separation steps. Also disclosed is the reaction of aqueous alkali metal hydroxide to produce 6-halo-2- substituted 2-nitroacetoacetanilides with 18% potas 55 hydroxyquinoxaline-4-oxide followed by dilution of the sium hydroxide. reaction mass to a suitable alkali metal hydroxide con Lacey J. Chem. Soc., 850 (1954) discloses the use of centration for subsequent processing; (c) contacting and triethylamine as a catalyst for reactions of diketene with reacting 6-halo-2-hydroxyquinoxaline-4-oxide with hy alkoxycarbonyl-amines to produce derivatives of aceto drogen to produce 6-halo-2-quinoxalinol which is sepa acetamide. The aromatic amine compounds studied do rated from the reaction mass and dried for subsequent not, however, include either nitro- or halogen substitu processing; and (d) contacting and reacting the 6-halo tion, which as electron withdrawing substituents, re 2-quinoxalinol with acid chloride to produce 2-chloro duce the basicity of the amine group. Such reduced 6-haloquinoxaline. Another aspect of this invention basicity is stated by Lacey to result in sluggish reaction. comprises the processes embodied by the individual Tennant J. Chem. Soc., 1963, 2428) describes the 65 steps (a), (b), (c), or (d) described above with their asso synthesis of unsubstituted 2-hydroxyquinoxaline-4- ciated preferred conditions. Recovery of the products oxide, and also its reduction with sodium dithionite in of the individual process steps is by conventional sepa acetic acid to produce 2-quinoxalinol. The yield was not ration or purification techniques. 4,636,562 3 DETAILED DESCRIPTION OF THE INVENTION R Equation 2 The process of this invention for preparing 2-chloro X N 6-haloquinoxaline compounds is exemplified by the aS reactions of Equations 1-4. As shown in Equation 1, II -adeousalkali metal G wherein X is chlorine, fluorine, or bromine, hydroxide N So H Equation 1 10 X NO2 a O III a R3N -- O in S The reaction depicted by Equation 2 is carried out by NH2 CH2 heating compound III in aqueous 3-20% by weight alkali metal hydroxide, preferably potassium hydroxide 15 or sodium hydroxide at 5-10% by weight concentra tion, to a temperature of from 70°-90° C., preferably 80' O C., for 0.5 to 3 hours. X NO The reaction of Equation 2, the second step of the 2 CH3 process invention, is preferably carried out by the fol 20 Sa lowing procedure: Solid compound II, either crude or N O recrystallized if desired, is added to an aqueous solution containing at least 4 equivalents of sodium hydroxide or H potassium hydroxide. Four equivalents or more of base II are employed in this step to ensure the presence of at 25 least 3 equivalents for the subsequent reduction step; the first step of the process involves reacting compound one equivalent is consumed in the cyclization. The mix I (4-halo-2-nitroaniline) with diketene to produce the ture is heated to the desired reaction temperature for 1 "corresponding substituted 4-halo-2-nitroacetoacetani hour, and then cooled to room temperature. The mix lide, compound II. This is conveniently carried out by ture is then diluted with water to produce the requisite 30 base concentration for direct, continued processing in contacting compound I with a 10% by weight excess of the third reaction step, or alternatively is acidified to diketene in the presence of a catalytic amount of a non precipitate solid compound III which can be filtered, nucleophilic amine, such as 1,4-diazabicyclo[2.2.2]oc washed with water, and dried under vacuum. tane (DABCO) or other trisubstituted aliphatic amine. The third step of the process involves the conversion The substituents on the trisubstituted aliphatic amine 35 of compound III to the corresponding 6-halo-2-quinox catalyst are C1-C4 alkyl, preferably triethyl, and the alinol of Formula IV by contacting with hydrogen in catalyst selected can be used in the 0.1-10% by weight the presence of a catalyst as shown in Equation 3.