Conversion of 2-pyrazolines to pyrazoles using bromine
View Patent ↗This invention relates to a method for preparing a compound of Formula 1 wherein L, R 1 , R 2 and X are as defined in the disclosure, comprising contacting a 2 pyrazoline of Formula 2 with bromine at a temperature of at least about 80° C. (Formula 1) (Formula 2). This invention also discloses preparation of a compound of Formula 3 wherein X, Z, R 5 , R 6 , R 7 , R 8a , R 8b and n are as defined in the disclosure, using a compound of Formula 1a wherein R 10 is as defined in the disclosure, prepared by the aforesaid method for preparing a compound of Formula 1. (Formula 3) (Formula 4).
1. A method for preparing a compound of Formula 1a
wherein
X is halogen, OR 3 or C 1 -C 4 haloalkyl;
Z is N or CR 9 ;
R 9 is H, halogen or C 1 -C 4 haloalkyl;
R 10 is H or C 1 -C 4 alkyl;
R 3 is H or C 1 -C 4 haloalkyl;
each R 5 is independently halogen or C 1 -C 4 haloalkyl; and
n is an integer from 0 to 3;
comprising:
contacting a 2-pyrazoline of Formula 2a
with bromine at a temperature of 120-140° C.
2. The method of claim 1 wherein
X is Br or CF 3 ;
Z is N;
each R 5 is independently halogen or CF 3 ; and
R 10 is methyl or ethyl.
3. The method of claim 1 wherein
X is OH, OCF 2 H or OCH 2 CF 3 ;
Z is N;
each R 5 is independently halogen or CF 3 ; and
R 10 is methyl or ethyl.
4. The method of claim 1 further comprising combining a base with the compound of Formula 2a either before or after contacting with the bromine and the molar equivalent of base relative to bromine is about 0:1 to 4:1.
5. The method of claim 1 wherein the bromine is present relative to the compound of Formula 2a at a molar equivalent of about 2:1 to 1:1.
6. The method of claim 1 further comprising combining a solvent with the compound of Formula 2a to form a mixture, before contacting the compound of Formula 2a with the bromine and the temperature is about the boiling point of the solvent.
7. The method of claim 1 further comprising adding the bromine as a gas to the compound of Formula 2a and the gaseous bromine is diluted with an inert gas.
8. The method of claim 6 wherein the solvent is an optionally halogenated hydrocarbon with a boiling point higher than 100° C.
9. The method of claim 8 wherein the solvent is an optionally chlorinated aromatic hydrocarbon or dibromoalkane.
10. The method of claim 8 wherein the optionally halogenated hydrocarbon is t-butylbenzene, chlorobenzene or 1,2-dibromoethane.
11. The method of claim 9 wherein the optionally halogenated hydrocarbon is chlorobenzene.
12. The method of claim 1 further comprising adding the bromine as a liquid to the compound of Formula 2a.
13. A method for preparing a compound of Formula 1a
wherein
X is halogen, OR 3 or C 1 -C 4 haloalkyl;
Z is N or CR 9 ;
R 9 is H, halogen or C 1 -C 4 haloalkyl;
R 10 is H or C 1 -C 4 alkyl;
R 3 is H or C 1 -C 4 haloalkyl;
each R 5 is independently halogen or C 1 -C 4 haloalkyl; and
n is an integer from 0 to 3;
comprising:
contacting a 2-pyrazoline of Formula 2a
in an optionally halogenated hydrocarbon solvent with a boiling point higher than 100° C. to form a mixture before contacting the 2-pyrazoline of Formula 2a with bromine.