Method for preparing 3-halo-4,5-dihydro-1H-pyrazoles

1. A method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I

wherein L is an optionally substituted carbon moiety;

each R is independently selected from optionally substituted carbon moieties;

k is an integer from 0 to 4;

and X 1 is halogen; comprising:

contacting a 4,5-dihydro-1H-pyrazole compound of Formula II

wherein X 2 is OS(O) m R 1 , OP(O) p (OR 2 ) 2 or a halogen other than X 1 ;

m is 1 or 2;

p is 0 or 1;

R 1 is selected from alkyl and haloalkyl; and phenyl optionally substituted with from 1 to 3 substituents selected from alkyl and halogen; and

each R 2 is independently selected from alkyl and haloalkyl; and phenyl optionally substituted with from 1 to 3 substituents selected from alkyl and halogen;

with a compound of the formula HX 1 in the presence of a suitable solvent.

2. The method of claim 1 wherein m is 2 and p is 1.

3. The method of claim 2 wherein X 2 is halogen or OS(O) m R 1 .

4. The method of claim 3 wherein X 2 is Cl or OS(O) m R 1 and R 1 is C 1 -C 2 alkyl, phenyl or 4-methylphenyl.

5. The method of claim 1 wherein X 1 is Cl or Br.

6. The method of claim 1 wherein the compound of Formula I is of Formula Ia

and the compound of Formula II is of Formula IIa

 wherein

each R 3 is independently C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 3 -C 6 halocycloalkyl, halogen, CN, NO 2 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylamino, C 2 -C 8 dialkylamino, C 3 -C 6 cycloalkylamino, (C 1 -C 4 alkyl)(C 3 -C 6 cycloalkyl)amino, C 2 -C 4 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminocarbonyl, C 3 -C 8 dialkylaminocarbonyl or C 3 -C 6 trialkylsilyl;

R 4 is H or an optionally substituted carbon moiety;

Z is N or CR 5 ;

R 5 is H or R 3 ; and

n is an integer from 0 to 3.

7. The method of claim 6 wherein R 4 is C 1 -C 4 alkyl.

8. The method of claim 7 wherein Z is N, n is 1, and R 3 is Cl or Br and is at the 3-position.

9. The method of claim 7 wherein X 1 is Br, X 2 is Cl or OS(O) m R 1 , m is 2, and R 1 is phenyl or 4-methylphenyl.

10. A method of preparing a compound of Formula III

wherein

X 1 is halogen;

each R 3 is independently C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 3 -C 6 halocycloalkyl, halogen, CN, NO 2 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylamino, C 2 -C 8 dialkylamino, C 3 -C 6 cycloalkylamino, (C 1 -C 4 alkyl)(C 3 -C 6 cycloalkyl)amino, C 2 -C 4 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminocarbonyl, C 3 -C 8 dialkylaminocarbonyl or C 3 -C 6 trialkylsilyl;

Z is N or CR 5 ;

R 5 is H or R 3 ;

R 6 is CH 3 , F, Cl or Br;

R 7 is F, Cl, Br, I or CF 3 ;

R 8a is C 1 -C 4 alkyl;

R 8b is H or CH 3 ; and

n is an integer from 0 to 3

using a compound of Formula Ia

wherein R 4 is H or an optionally substituted carbon moiety, by for example,

(1) providing a compound of Formula 6 wherein R 4 is H by (a) oxidizing a compound of Formula Ia to form a compound of Formula 6;

(b) if R 4 for the compound of Formula 6 formed in (a) is an optionally substituted carbon moiety, hydrolyzing said compound of Formula 6 formed in (a);

(2) providing a compound of Formula 8 either by (c) coupling said compound of Formula (6) wherein R 4 is H provided in (1) with a compound of Formula 7; or by

(d1) chlorinating said compound of Formula 6 wherein R 4 is H provided in (1) to form a compound of Formula 10; and

(d2) coupling said compound of Formula 10 with a compound of Formula 9; and

(3) reacting said compound of Formula 8 provided in (2) with a compound of Formula 11;

R 8a (R 8b )NH  (11);

 charactarized by:

preparing said copound of Formula Ia by the method of claim 6 .

11. The method of claim 10 wherein R 4 in the compound of Formula Ia is C 1 -C 4 alkyl.

12. The method of claim 11 wherein Z is N, n is 1, and R 3 is Cl or Br and is at the 3-position.

13. The method of claim 11 wherein X 1 is Br, X 2 is Cl or OS(O) m R 1 , m is 2, and R 1 is phenyl or 4-methylphenyl.