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(12) United States Patent (10) Patent No.: US 6,388,135 B1 L0chtman Et Al

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(12) United States Patent (10) Patent No.: US 6,388,135 B1 L0chtman Et Al USOO6388135B1 (12) United States Patent (10) Patent No.: US 6,388,135 B1 L0chtman et al. (45) Date of Patent: May 14, 2002 (54) PREPARATION OF 4-BROMOANILINE WO WO 98/31681 7/1998 DERVATIVES WO WO 99/58509 11/1999 (75) Inventors: Rene Lochtman, Mannheim; Michael OTHER PUBLICATIONS Keil, Freinsheim; Joachim Gebhardt, Wachenheim; Michael Rack, Miller et al. “Methoden Der Organischen Chemie' Band Heidelberg; Wolfgang von Deyn, V/4 (1960) pp. 240–242 & 274-249. Neustadt, all of (DE) (73) Assignee: BASF Aktiengesellschaft, Primary Examiner Samuel Barts Ludwigshafen (DE) (74) Attorney, Agent, or Firm-Keil & Weinkauf (*) Notice: Subject to any disclaimer, the term of this (57) ABSTRACT patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. A process for preparing 4-bromoaniline derivatives of the formula I (21) Appl. No.: 09/894,006 (22) Filed: Jun. 29, 2001 Related U.S. Application Data Br R2 (60) Provisional application No. 60/219,410, filed on Jul. 20, 2000. (30) Foreign Application Priority Data Jun. 30, 2000 (DE) ......................................... 10O3O 975 where: (51) Int. Cl." .............................................. C07C 209/00 (52) U.S. Cl. ....................... 564/412; 548/240; 548/247; R" is C1-Co-alkyl, C-C-haloalkyl, C1-Co-alkoxy, 558/418 C-C-haloalkoxy, C-C-cycloalkyl, halogen (58) Field of Search .......................... 564/412; 548/240, R is C-C-alkyl, C-C-alkoxy, Ca-Cs-cycloalkyl, 548/247; 558/418 C-C-alkenyl, cyano or a heterocyclic radical is described. (56) References Cited FOREIGN PATENT DOCUMENTS CA 22783.31 7/1998 30 Claims, No Drawings US 6,388,135 B1 1 2 PREPARATION OF 4-BROMOANILINE which comprises reacting a compound of the formula II DERVATIVES II R1 The present application claims priority of prior provi sional application Serial No. 60/219,410, filed on Jul. 20, 2OOO. The present invention provides a process for preparing 4-bromoaniline derivatives. 4-Bromoaniline derivatives are useful compounds which are used as intermediates in chemical industry. They are in which R" and Rare as defined above with a brominating Suitable, for example, for preparing active compounds used agent in the Solvent pyridine or in a Solvent mixture com in the field of crop protection, or for preparing pharmaceu prising at least 55% by wight of pyridine. tically active compounds. WO 99/58509, for example, 15 With the aid of the process according to the invention, it describes processes for preparing isoxazolin-3- is possible to obtain the aniline derivatives of the formula I in higher yields than with the prior-art preparation processes. ylacylbenzenes in which 4-bromoaniline derivatives are Thus, for example, the compound 4-bromo-2-(4,5- employed as intermediates for preparing herbicidally active dihydroisoxazol-3-yl)-3-methylaniline can be obtained by compounds. WO 98/31681 describes these active com the process described in WO 99/58509 (cf. Example 10 pounds (2-alkyl-3-(4,5-dihydroisoxazol-3-yl)acylbenzenes) therein) in a yield of only 47%, whereas the yield in the as herbicidally active compounds. process according to the invention is at least 60%, preferably It is known from the literature that the selective bromi at least 70% or 80%, and in particular at least 90%. nation of anilines in the para position is impossible, or Moreover, the compounds of the formula I are obtained in possible only with difficulty (Houben-Weyl 5/4, 241,274 f). 25 higher purity. Here, the bromination takes place with high In general, bromination with elemental bromine is not Selectivity in the 4-position of the phenyl ring. The Selec Selective, but frequently associated with the formation of tivity (ratio of monobromo to dibromo compound) is at least 92:8, in particular at least 95:5. Surprisingly, the proportion considerable amounts of dibromo compounds. According to of impurities, Such as, for example, dibromides (these dibro experience, the Selectivities for monobromo to dibromo mides are derivatives of the formula I which are Substituted compounds are in an order of magnitude of about 9:1, i.e. the in the 5- or 6-position by a further bromine atom) which are proportion of undesired dibromo compounds is about 10%. difficult to remove from the resulting reaction mixture, or Thus, only with expensive reagents, Such as tetrabutylam whose removal requires relatively high technical monium tribromide, the compound 4-bromo-2-(4,5- expenditure, is less than 5%. Accordingly, the number of dihydroisoxazol-3-yl)-3-methylaniline, for example, was further additional purification Steps for isolation and work obtained at -30° C. in a yield of about 50% (cf. WO 35 up of the compounds I prepared by the process according to 99/58509). the invention can be reduced. This is particularly advanta It is an object of the present invention to provide an geous for the industrial production of the compounds I, Since a more efficient and more cost-effective process can be alternative process for preparing 4-bromoaniline deriva provided. tives. The preparation process described in WO 99/58509 40 Owing to the high Selectivity and the Small proportion of for the 4-bromo-2-(4,5-dihydro isoxazol-3-yl)-3- dibromo compounds, it is possible, if appropriate, to use the methylaniline derivatives gives unsatisfactory yields and an reaction product even without additional purification for the unsatisfactory purity of the products. Accordingly, the pro next process Steps for further conversion into Suitable end cess described in WO99/58509 is only of limited use for the products. industrial preparation of Such compounds. 45 C-C-Alkyl is a straight-chain or branched alkyl group We have found that this object is achieved by a process having 1-6 carbon atoms, Such as, for example, methyl, for preparing 4-bromoaniline derivatives of the formula I ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert.-butyl, n-pentyl or n-hexyl, preference is given to C-C-alkyl, Such as, for example, methyl, ethyl, n-propyl, isopropyl, 50 n-butyl, isobutyl or tert-butyl. C-C-haloalkyl is a Straight-chain or branched C-C- Br alkyl group as mentioned above which is partially or fully substituted by fluorine, chlorine, bromine and/or iodine, for example chloromethyl, dichloromethyl, trichloromethyl, 55 fluoromethyl, difluoromethyl, trifluoromethyl, NH2 chlorofluoro methyl, dichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2- where: trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2,- 60 difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2- R" is C1-Co-alkyl, C-C-haloalkyl, C-C-alkoxy, trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, C-C-haloalkoxy, C-C-cycloalkyl, halogen 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, R is C1-Co-alkyl, C1-Co-alkoxy, Ca-Cs-cycloalkyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3.3, C-C-alkenyl, cyano or a heterocyclic radical, 65 3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, US 6,388,135 B1 3 4 heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, C-C-Cycloalkyl is an unsubstituted or Substituted 1-(chloromethyl)-2-chloroethyl, 1-(bromoethyl)-2- cycloalkyl ring having 3-8 carbon atoms, Such as, for bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, nonafluorobutyl, 5-fluorop enty 1, 5-chlorope nty 1, cycloheptyl or cyclooctyl, Suitable Substituents are, for 5-brom openty 1, 5-iodopentyl, unde cafluorope nty 1, example: C-C-alkyl, C-C-alkoxy or halogen; prefer 6-fluorohexyl, 6-chlorohexyl, 6-bromohexyl, 6-iodohexyl ence is given to C-C-cycloalkyl, which is unsubstituted, and dodecafluorohexyl, perference is given to C-C- Such as, for example cyclopropyl, cyclopentyl or cyclo haloalkyl, Such as chloromethyl, dichloromethyl, hexyl, trichloromethyl, fluoromethyl, difluoromethyl, C-C-alkenyl is a Straight-chain or branched alkenyl trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, group having 2–6 carbon atoms, wherein the double bond is chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, located at the connecting position, Such as for example 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2- ethenyl, prop-1-en-1-yl, 1-methylethenyl, buten-1-yl, trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2,- 1-methylprop-1-en-1-yl, 2-methylprop-1-en-1-yl, penten-1- difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2- yl, 1-methyl-but-1-en-1-yl, 2-methyl-but-1-en-1-yl, trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 15 3-methyl-but-1-en-1-yl, 1,2-dimethyl-prop-1-en-1-yl, heX 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, 1-en-1-yl, 1-methylpent-1-en-1-yl, 2-methylpent-1-en-1-yl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 3-methylpent-1-en-1-yl, 4-methylpent-1-en-1-yl, 1,2- 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3.3, dimethylbut-1-en-1-yl, 1,3-dimethylbut-1-en-1-yl, 2,3- 3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, dimethylbut-1-en-1-yl, 3,3-dimethylbut-1-en-1-yl, heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-ethylbut-1-en-1-yl, 2-ethylbut-1-en-1-yl or 1-ethyl-2- 1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2- methylprop-1-en-1-yl; bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, or Halogen is fluorine, chlorine, bromine, is particular chlo nonafluorobutyl; rine or bromine. C-C-Alkoxy is a Straight-chain or branched alkyl group “Heterocyclic ring is a Saturated, unsaturated or partially having 1-6 carbon atoms, Such as, for example, methoxy, 25 unsaturated heterocycle having 3-8 ring atoms and one, two ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, or three oxygen, Sulfur or nitrogen atoms. Preference is tert.-butyloxy, n-pentyloxy or n-hexyloxy, preference is given to heterocycles which contain at least one oxygen given to C-C-alkoxy, Such as, for example, methoxy, and/or one nitrogen atom.
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