PROCESS FOR PREPARATION OF 5-BROMO-1,3-DICHLORO-2-FLUORO-BENZENE

Abstract

The invention relates to a process for the preparation of 5-bromo-1,3-dichloro-2-fluoro-benzene by diazotization and reduction of 6-bromo-2,4-dichloro-3-fluoro-aniline, which is obtained by bromination of 2,4-dichloro-3-fluoro-aniline, which is obtained by reduction of 1,3-dichloro-2-fluoro-4-nitro-benzene, and a process for preparing active compounds of formula V (Formula V) wherein the variables are defined in the specification by further transforming 5-bromo-1,3-dichloro-2-fluoro-benzene obtained from 2,4-dichloro-3-fluoro-aniline by the process according to the invention.

##STR00001##

Claims

1. A process for preparing 5-bromo-1,3-dichloro-2-fluoro-benzene comprising diazotizing 6-bromo-2,4-dichloro-3-fluoro-aniline and reducing the resulting diazonium salt to yield 5-bromo-1,3-dichloro-2-fluoro-benzene.

2. The process of claim 1, wherein 6-bromo-2,4-dichloro-3-fluoro-aniline is obtained by brominating 2,4-dichloro-3-fluoro-aniline.

3. The process of claim 2, wherein 2,4-dichloro-3-fluoroaniline is obtained by reducing 1,3-dichloro-2-fluoro-4-nitro-benzene.

4. The process of claim 3, wherein the reduction is conducted with hydrogen on Pd/C catalyst.

5. The process of claim 2, wherein the bromination is conducted with bromine and an oxidation agent.

6. The process of claim 5, wherein the oxidation agent is H.sub.2O.sub.2.

7. The process of claim 1, wherein the diazotization is conducted with NaNO.sub.2.

8. The process of claim 1, wherein the reduction of the diazonium salt is effected with hypophosphoric acid.

9. 6-bromo-2,4-dichloro-3-fluoro-aniline.

10. A process for preparing a compound of formula V ##STR00016## wherein X is CH, O, or S, U is CH or N; each R.sup.2 is independently H, halogen, CN, N.sub.3, NO.sub.2, SCN, SF.sub.5, C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.8-cycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted with one or more same or different R.sup.8, Si(R.sup.12).sub.3, OR.sup.9, S(O).sub.nR.sup.9, NR.sup.10aR.sup.10b, phenyl which is unsubstituted or partially or fully substituted with R.sup.11, and a 3- to 10-membered saturated, partially or fully unsaturated heteromonocyclic or heterobicyclic ring containing 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or substituted with one or more same or different R.sup.11; n is 0, 1, or 2; G.sup.1, G.sup.2 are each CR.sup.3, or together form a sulfur atom; each R.sup.3 is independently selected from the meanings mentioned for R.sup.2, or two R.sup.3 bonded to adjacent carbon atoms may form a five- or sixmembered saturated, partially or fully unsaturated carbocyclic ring, or a dihydrofurane, or R.sup.3 bonded to carbon atom in position G.sup.1 form a bond to the chain *-Q-Z— in group A.sup.2; A is a group A.sup.1, A.sup.2, A.sup.3, or A.sup.4; wherein A.sup.1 is C(═W)Y; W is O, or S; Y is N(R.sup.5)R.sup.6, or OR.sup.9; A.sup.2 is ##STR00017## wherein # denotes the bond of group A, and % denotes the bond to G.sup.1; Q-Z is %—CH.sub.2—O—*, ‘%—CH.sub.2—S(O).sub.n—*, or %—C(═O)—O—*, wherein % marks the bond of Q to phenyl, and * the bond of Z to azetidin; and R.sup.A4 is H or C(═O)R.sup.4A, wherein R.sup.4A is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-haloalkynyl, C.sub.1-C.sub.4-alkylcarbonyl, which aliphatic groups are unsubstituted or substituted with one or more radicals R.sup.41; C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl which cyclic groups are unsubstituted or substituted with one or more R.sup.42; C(═O)N(R.sup.43)R.sup.44, N(R.sup.43)R.sup.45, CH═NOR.sup.46; phenyl, heterocycle, or hetaryl HET which rings are unsubstituted or partially or fully substituted with R.sup.A; R.sup.41 is independently OH, CN, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, S(O).sub.n—C.sub.1-C.sub.6-alkyl, S(O).sub.n—C.sub.1-C.sub.6-haloalkyl, C(═O)N(R.sup.43)R.sup.44, C.sub.3-C.sub.6-cycloalkyl, or C.sub.3-C.sub.6-halocycloalkyl which cycles are unsubstituted or substituted with one or more R.sup.411; or phenyl, heterocycle or hetaryl HET which rings are unsubstituted or partially or fully substituted with R.sup.A; R.sup.411 is independently OH, CN, C.sub.1-C.sub.2-alkyl, or C.sub.1-C.sub.2-haloalkyl; R.sup.43 is H, or C.sub.1-C.sub.6-alkyl, R.sup.44 is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-haloalkynyl, or C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, or C.sub.3-C.sub.6-halocycloalkylmethyl which rings are unsubstituted or substituted with a cyano; R.sup.45 H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, CH.sub.2—CN, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, C.sub.3-C.sub.6-halocycloalkylmethyl, phenyl and hetaryl HET which aromatic rings are unsubstituted or partially or fully substituted with R.sup.A; R.sup.42 C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, or a group as defined for R.sup.41; R.sup.46 is independently H, C.sub.1-C.sub.6-alkyl, or C.sub.1-C.sub.6-haloalkyl; R.sup.A is independently selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.2-C.sub.4-haloalkynyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, S(O).sub.n—C.sub.1-C.sub.4-alkyl, S(O).sub.n—C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C(═O)N(R.sup.43)R.sup.44; or two R.sup.A present on the same carbon atom of a saturated or partially saturated ring may form together ═O or ═S; or two R.sup.A present on the same S or SO ring member of a heterocyclic ring may together form a group ═N(C.sub.1-C.sub.6-alkyl), ═NO(C.sub.1-C.sub.6-alkyl), ═NN(H)(C.sub.1-C.sub.6-alkyl) or ═NN(C.sub.1-C.sub.6-alkyl).sub.2; A.sup.3 is CH.sub.2—NR.sup.5C(═W)R.sup.6; A.sup.4 is cyano; R.sup.5 is independently selected from the meanings mentioned for R.sup.2; R.sup.6 is H, CN, C.sub.1-C.sub.10-alkyl, C.sub.3-C.sub.8-cycloalkyl, C.sub.2-C.sub.10-alkenyl, C.sub.2-C.sub.10-alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted with one or more same or different R.sup.8; or S(O).sub.nR.sup.9, or C(═O)R.sup.8; a 3- to 8-membered saturated, partially or fully unsaturated heterocyclic ring, which ring may contain 1, 2, 3, or 4 heteroatoms O, S, N, C═O and/or C═S as ring members, which heterocyclic ring is unsubstituted or partially or fully substituted with same or different halogen, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.3-C.sub.8-cycloalkyl, C.sub.3-C.sub.8-halocycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R.sup.8, or phenyl which may be partially or fully substituted with R.sup.11; or R.sup.5 and R.sup.6, together with the nitrogen atom to which they are bound, form a 3- to 8-membered saturated, partially or fully unsaturated heterocyclic ring, which ring may contain 1, 2, 3, or 4 heteroatoms O, S, N, C═O and/or C═S as ring members, which heterocyclic ring is unsubstituted or partially or fully substituted with same or different halogen, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.3-C.sub.8-cycloalkyl, C.sub.3-C.sub.8-halocycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R.sup.8, or phenyl which may be partially or fully substituted with R.sup.11; or R.sup.5 and R.sup.6 together form a group ═C(R.sup.8).sub.2, ═S(O).sub.m(R.sup.9).sub.2, ═NR.sup.10a, or ═NOR.sup.9; R.sup.7a, R.sup.7b are each independently H, halogen, CN, C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.8-cycloalkyl, C.sub.2-C.sub.6-alkenyl, or C.sub.2-C.sub.6-alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted with same or different R.sup.8; each R.sup.8 is independently CN, N.sub.3, NO.sub.2, SCN, SF.sub.5, C.sub.3-C.sub.8-cycloalkyl, C.sub.3-C.sub.8-halocycloalkyl, wherein the carbon chains may be substituted with one or more R.sup.13; Si(R.sup.12).sub.3, OR.sup.9, OSO.sub.2R.sup.9, S(O).sub.nR.sup.9, N(R.sup.10a)R.sup.10b, C(═O)N(R.sup.10a)R.sup.10b, C(═S)N(R.sup.10a)R.sup.10b, C(═O)OR.sup.9, CH═NOR.sup.9, phenyl, which is unsubstituted or partially or fully substituted with same or different R.sup.16, or a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted or partially or fully substituted with same or different R.sup.16, or two R.sup.8 present on the same carbon atom of an alkyl, alkenyl, alkynyl or cycloalkyl group together form a group ═O, ═C(R.sup.13).sub.2; ═S; ═S(O).sub.m(R.sup.15).sub.2, ═S(O).sub.mR.sup.15N(R.sup.14a)R.sup.14b, ═NR.sup.10a, ═NOR.sup.9; or ═NN(R.sup.10a)R.sup.10b; or two radicals R.sup.8, together with the carbon atoms of the alkyl, alkenyl, alkynyl or cycloalkyl group which they are bonded to, form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated or partially unsaturated carbocyclic or heterocyclic ring, which heterocyclic ring comprises 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, and which ring is unsubstituted, or partially or fully substituted with same or different R.sup.16; and R.sup.8 as a substituent on a cycloalkyl ring may additionally be C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, and C.sub.2-C.sub.6-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R.sup.13; and R.sup.8 in the groups C(═O)R.sup.8 and ═C(R.sup.8).sub.2 may additionally be H, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, or C.sub.2-C.sub.6-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R.sup.13; each R.sup.9 is independently H, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.8-cycloalkyl, C.sub.3-C.sub.8-cycloalkyl-C.sub.1-C.sub.4-alkyl-, C.sub.3-C.sub.8-halocycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, or C.sub.2-C.sub.6-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R.sup.13, or C.sub.1-C.sub.6-alkyl-C(═O)OR.sup.15, C.sub.1-C.sub.6-alkyl-C(═O)N(R.sup.14a)R.sup.14b, C.sub.1-C.sub.6-alkyl-C(═S)N(R.sup.14a)R.sup.14b, C.sub.1-C.sub.6-alkyl-C(═NR.sup.14)N(R.sup.14a)R.sup.14b, Si(R.sup.12).sub.3, S(O).sub.nR.sup.15, S(O).sub.nN(R.sup.14a)R.sup.14b, N(R.sup.10a)R.sup.10b, N═C(R.sup.13).sub.2, C(═O)R.sup.13, C(═O)N(R.sup.14a)R.sup.14b, C(═S)N(R.sup.14a)R.sup.14b, C(═O)OR.sup.15, or phenyl, which is unsubstituted, or partially or fully substituted with R.sup.16; and a 3- to 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R.sup.16; and R.sup.9 in the groups S(O).sub.nR.sup.9 and OSO.sub.2R.sup.9 may additionally be C.sub.1-C.sub.6-alkoxy, or C.sub.1-C.sub.6-haloalkoxy; R.sup.10a, R.sup.10b are independently from one another H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.5-cycloalkyl, C.sub.3-C.sub.5-halocycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R.sup.13; C.sub.1-C.sub.6-alkyl-C(═O)OR.sup.15, C.sub.1-C.sub.6-alkyl-C(═O)N(R.sup.14a)R.sup.14b, C.sub.1-C.sub.6-alkyl-C(═S)N(R.sup.14a)R.sup.14b, C.sub.1-C.sub.6-alkyl-C(═NR.sup.14)N(R.sup.14a)R.sup.14b, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, S(O).sub.nR.sup.15, S(O).sub.nN(R.sup.14a)R.sup.14b, C(═O)R.sup.13, C(═O)OR.sup.15, C(═O)N(R.sup.14a)R.sup.14b, C(═S)R.sup.13, C(═S)SR.sup.15, C(═S)N(R.sup.14a)R.sup.14b, C(═NR.sup.14)R.sup.13; phenyl, which is unsubstituted, or partially or fully substituted with same or different R.sup.16; and a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R.sup.16; or R.sup.10a and R.sup.10b together with the nitrogen atom they are bonded to form a 3- to 8-membered saturated, partially or fully unsaturated heterocyclic ring, which ring may additionally contain one or two heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.3-C.sub.8-cycloalkyl, C.sub.3-C.sub.8-halocycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-haloalkynyl, phenyl which may be partially or fully substituted with R.sup.16, and a 3-, 4-, 5-, 6,- or 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R.sup.16; or R.sup.10a and R.sup.10b together form a group ═C(R.sup.13).sub.2, ═S(O).sub.m(R.sup.15).sub.2, ═S(O).sub.mR.sup.15N(R.sup.14a)R.sup.14b, ═NR.sup.14, or ═NOR.sup.15; R.sup.11 is halogen, CN, N.sub.3, NO.sub.2, SCN, SF.sub.5, C.sub.1-C.sub.10-alkyl, C.sub.3-C.sub.8-cycloalkyl, C.sub.2-C.sub.10-alkenyl, C.sub.2-C.sub.10-alkynyl, which groups are unsubstituted, partially or fully halogenated, and/or may be substituted with same or different R.sup.8, or OR.sup.9, NR.sup.10aR.sup.10b, S(O).sub.nR.sup.9, Si(R.sup.12).sub.3; phenyl, which is unsubstituted, or partially or fully substituted with same or different R.sup.16; and a 3- to 7-membered saturated, partially or fully unsaturated aromatic heterocyclic ring comprising 1, 2, 3, or 4 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R.sup.16; or two R.sup.11 present on the same ring carbon atom of an unsaturated or partially unsaturated heterocyclic ring may together form a group ═O, ═C(R.sup.13).sub.2, ═S, ═S(O).sub.m(R.sup.15).sub.2, ═S(O).sub.mR.sup.15N(R.sup.14a)R.sup.14b, ═NR.sup.14, ═NOR.sup.15, or ═NN(R.sup.14a)R.sup.14b; or two R.sup.11 bound on adjacent ring atoms form together with the ring atoms to which they are bound a saturated 3- to 9-membered ring, which ring may contain 1 or 2 heteroatoms O, S, N, and/or NR.sup.14, and/or 1 or 2 groups C═O, C═S, C═NR.sup.14 as ring members, and which ring is unsubstituted, or partially or fully substituted with same or different halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.3-C.sub.8-cycloalkyl, C.sub.3-C.sub.8-halocycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-haloalkynyl, phenyl which may be partially or fully substituted with same or different R.sup.16, and a 3- to 7-membered saturated, partially or fully unsaturated heterocyclic ring containing 1, 2, or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R.sup.16; each R.sup.12 is independently C.sub.1-C.sub.4-alkyl and phenyl, which is unsubstituted, or partially or fully substituted with same or different C.sub.1-C.sub.4-alkyl; each R.sup.13 is independently CN, NO.sub.2, OH, SH, SCN, SF.sub.5, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, SO.sub.n—C.sub.1-C.sub.6-alkyl, SO.sub.n—C.sub.1-C.sub.6-haloalkyl, Si(R.sup.12).sub.3, —C(═O)N(R.sup.14a)R.sup.14b, C.sub.3-C.sub.8-cycloalkyl which is unsubstituted, partially or fully halogenated or substituted with 1 or 2 same or different C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy and/or oxo; phenyl, benzyl, phenoxy, where the phenyl moiety may be substituted with one or more same or different R.sup.16; and a 3- to 7-membered saturated, partially or fully unsaturated heterocyclic ring containing 1, 2, or 3 heteroatoms N, O, and/or S, as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R.sup.16; or two R.sup.13 present on the same carbon atom of an alkyl, alkenyl, alkynyl or cycloalkyl group may together be ═O, ═CH(C.sub.1-C.sub.4-alkyl), ═C(C.sub.1-C.sub.4-alkyl)C.sub.1-C.sub.4-alkyl, ═N(C.sub.1-C.sub.6-alkyl) or ═NO(C.sub.1-C.sub.6-alkyl); and R.sup.13 as a substituent of a cycloalkyl ring may additionally be C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl or C.sub.2-C.sub.6-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted with 1 or 2 CN, C.sub.3-C.sub.4-cycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, and oxo; and R.sup.13 in groups ═C(R.sup.13).sub.2, N═C(R.sup.13).sub.2, C(═O)R.sup.13, C(═S)R.sup.13, and C(═NR.sup.14)R.sup.13 may additionally be H, halogen, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, or C.sub.2-C.sub.6-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted with 1 or 2 CN, C.sub.3-C.sub.4-cycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, and oxo; each R.sup.14 is independently H, CN, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, SO.sub.n—C.sub.1-C.sub.6-alkyl, SO.sub.n—C.sub.1-C.sub.6-haloalkyl, Si(R.sup.12).sub.3; C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted with 1 or 2 CN, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, SO.sub.n—C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl which is unsubstituted or substituted with 1 or 2 substituents halogen and CN; and oxo; C.sub.3-C.sub.8-cycloalkyl which is unsubstituted, or partially or fully halogenated or substituted with 1 or 2 CN, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, SO.sub.nC.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.3-C.sub.4-cycloalkyl-C.sub.1-C.sub.4-alkyl-, which groups are unsubstituted, or substituted with 1 or 2 substituents selected from halogen and CN; phenyl, benzyl, pyridyl, phenoxy, which cyclic moieties are unsubstituted, or substituted with one or more same or different halogen, CN, NO.sub.2, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.2-C.sub.4-haloalkynyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, and C.sub.1-C.sub.6-alkoxycarbonyl; and a 3-, 4-, 5- or 6-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different R.sup.16; R.sup.14a and R.sup.14b independently of each other, have one of the meanings given for R.sup.14; or R.sup.14a and R.sup.14b, together with the nitrogen atom to which they are bound, form a 3- to 7-membered saturated, partially, or fully unsaturated heterocyclic ring, wherein the ring may additionally contain 1 or 2 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, or C.sub.1-C.sub.4-haloalkoxy; or R.sup.14a and R.sup.14 or R.sup.14b and R.sup.14, together with the nitrogen atoms to which they are bound in the group C(═NR.sup.14)N(R.sup.14a)R.sup.14b, form a 3- to 7-membered partially, or fully unsaturated heterocyclic ring, wherein the ring may additionally contain 1 or 2 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different halogen, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, or C.sub.1-C.sub.4-haloalkoxy; each R.sup.15 is independently H, CN, Si(R.sup.12).sub.3 C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted with 1 or 2 radicals C.sub.3-C.sub.4-cycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, SO.sub.n—C.sub.1-C.sub.6-alkyl, or oxo; C.sub.3-C.sub.8-cycloalkyl which is unsubstituted, partially or fully halogenated or substituted with 1 or 2 radicals C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, SO.sub.n—C.sub.1-C.sub.6-alkyl, or oxo; phenyl, benzyl, pyridyl, and phenoxy, which rings are unsubstituted, partially or fully halogenated, or substituted with 1, 2 or 3 substituents C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, or (C.sub.1-C.sub.6-alkoxy)carbonyl; each R.sup.16 is independently halogen, NO.sub.2, CN, OH, SH, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, SO.sub.n—C.sub.1-C.sub.6-alkyl, SO.sub.n—C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.1-C.sub.4-haloalkoxycarbonyl, aminocarbonyl, C.sub.1-C.sub.4-alkylaminocarbonyl, di-(C.sub.1-C.sub.4-alkyl)-aminocarbonyl, Si(R.sup.12).sub.3; C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted with 1 or 2 radicals CN, C.sub.3-C.sub.4-cycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, or oxo; C.sub.3-C.sub.8-cycloalkyl which is unsubstituted, partially or fully halogenated or substituted with 1 or 2 radicals CN, C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, or oxo; phenyl, benzyl, pyridyl and phenoxy, which rings are unsubstituted, partially or fully halogenated, or substituted with 1, 2 or 3 substituents C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, or (C.sub.1-C.sub.6-alkoxy)carbonyl; or two R.sup.16 present together on the same atom of an unsaturated or partially unsaturated ring may be ═O, ═S, ═N(C.sub.1-C.sub.6-alkyl), ═NO—C.sub.1-C.sub.6-alkyl, ═CH(C.sub.1-C.sub.4-alkyl), or ═C(C.sub.1-C.sub.4-alkyl).sub.2; or two R.sup.16 on two adjacent carbon atoms form together with the carbon atoms they are bonded to a 4- to 8-membered saturated, partially or fully unsaturated ring, wherein the ring may contain 1 or 2 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted with same or different halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, or C.sub.1-C.sub.4-haloalkoxy; each m is independently 0, or 1; comprising preparing 5-bromo-1,3-dichloro-2-fluorobenzene according to claim 1, further transforming it to VI, ##STR00018## reacting VI to VII, ##STR00019## and cyclizing VII to yield V.

11. The process of claim 10, wherein the formula V corresponds to formula V.A ##STR00020## wherein W is CH or O, R.sup.5 is H or CH.sub.3, and R.sup.6 is H, C.sub.1-C.sub.6-alkyl, or C.sub.2-C.sub.6-alkenyl.

12. The process of claim 10, wherein the formula V corresponds to formula V.B ##STR00021## wherein G.sup.1 is CH, and G.sup.2 is CR.sup.3; wherein R.sup.3 is halogen, or C.sub.1-C.sub.2-alkyl; p is 1 or 2; R.sup.x5 is H or CH.sub.3, and R.sup.x6 is CH.sub.3, C.sub.2H.sub.5, CH.sub.2(CH.sub.3).sub.2, CH.sub.2CH═CH.sub.2, CH.sub.2CF.sub.3, CH.sub.2CH.sub.2CF.sub.3, CH.sub.2C.sub.6H.sub.5, or CH.sub.2C(═O)OCH.sub.3;

Description

EXAMPLES

A. Preparation Examples

[0208] With appropriate modification of the starting materials, the procedures given in the synthesis description were used to obtain further compounds I. The compounds obtained in this manner are listed in the table that follows, together with physical data.

[0209] The products shown below were characterized by melting point determination, by NMR spectroscopy or by the masses ([m/z]) or retention time (RT; [min.]) determined by HPLC-MS or HPLC spectrometry.

[0210] HPLC-MS=high performance liquid chromatography-coupled mass spectrometry;

[0211] HPLC method A: HPLC Phenomenex Kinetex 1.7 μm XB-C18 100 A, 50×2.1 mm”, Mobile Phase: A: water+0.1% TFA; B:CAN; Temperature: 60° C.; Gradient:5% B to 100% B in 1.50 min; 100% B 0.25 min; Flow: 0.8 ml/min to 1.0 ml/min in 1.51 min; MS method: ESI positive; Mass range (m/z): 100-700″.

[0212] HPLC method B: HPLC method: Phenomenex Kinetex 1.7 μm XB-C18 100 A; 50×2.1 mm; mobile phase: A: water+0.1% trifluoroacetic acid (TFA); B: acetonitrile; gradient: 5-100% B in 1.50 minutes; 100% B 0.25 min; flow: 0.8-1.0 ml/min in 1.51 minutes at 60° C. MS: ESI positive, m/z 100-1400.

Example 1: Preparation of 2,4-dichloro-3-fluoro-aniline

[0213] A mixture of 1,3-dichloro-2-fluoro-4-nitro-benzene (24.9 g, 0.119 mol, 1.00 equiv.), Pt/C 5%/V 2.5% (2.00 g) and methanol (250 mL) was charged into a hydrogenation apparatus and flushed with hydrogen gas. A constant pressure of 0.1 bar hydrogen was kept throughout the reaction and the mixture was stirred at 2000 rpm keeping the temperature between 24-27° C. by cooling. After 0.5 h, the reaction was completed, and the catalyst was filtered off using a plug of celite. The filtrate was concentrated in vacuum to yield the title compound (21.1 g, purity 93%, yield 92%).

[0214] .sup.1H NMR: (400 MHz, CDCl.sub.3): δ 4.09 (br. s, 2H), 6.60 (m, 1H), 7.06 (m, 1H) ppm.

Example 2: Preparation of 6-bromo-2,4-dichloro-3-fluoro-aniline

[0215] To a mixture of 2,4-dichloro-3-fluoro-aniline (20.9 g, 0.110 mmol, 1.00 equiv.) and glacial acetic acid (92.7 g, 1.54 mol, 14 equiv.) was added bromine (10.58 g, 0.066 mol, 0.600 equiv.) at 20-22° C. within 25 min. After 5 min, hydrogen peroxide solution (50% in water, 4.502 g, 0.066 mol, 0.600 equiv.) was added and the temperature was maintained between 20-22° C. After 15 min, the reaction was completed and poured onto ice-water (300 mL). Excess of bromine was quenched by the addition of aqueous sodium sulfite solution. The resulting solids were collected by filtration and washed with water. Drying in vacuum at 40° C. yielded the title compound (29.60 g, purity 95%, yield 99%)

[0216] .sup.1H NMR: (400 MHz, CDCl.sub.3): δ 4.61 (br. s, 2H), 7.40 (m, 1H) ppm.

Example 3: Preparation of 5-bromo-1,3-dichloro-2-fluoro-benzene

[0217] A mixture of 6-bromo-2,4-dichloro-3-fluoro-aniline (29.5 g, 0.108 mmol, 1.00 equiv.) and concentrated hydrochloric acid (32% in water, 117 mL. 1.19 mol, 11 equiv.) was kept at 50° C. for 10 min and water was added. The resulting suspension was cooled to 0° C. and an aqueous solution of sodium nitrite (40.62 g, 25%, 0.147 mol, 1.40 equiv.) was added within 30 min, keeping the temperature between 0-2° C. for 1 h.

[0218] In a second flask, an aqueous solution of hypophosphoric acid (528 g, 50%, 4.01 mol, 37 equiv.) was heated to 90° C. and the diazonium solution from above was added within 10 min. After another 20 min at 85-90° C., the reaction was complete. The mixture was cooled and extracted with methylene chloride, combined organic layers were washed with water and dried over anhydrous magnesium sulfate. After filtration, the mother liquid was concentrated in vacuum to yield the title compound (23.5 g, purity 93%, yield 83%).

[0219] .sup.1H NMR: (400 MHz, CDCl.sub.3): δ 7.46 (m, 1H) ppm.