Method for preparing 3-trifluoromethyl chalcones
Disclosed is a method for preparing a compound of Formula 1 wherein Q and Z are as defined in the disclosure comprising distilling water from a mixture comprising a compound of Formula 2, a compound of Formula 3, a base comprising at least one compound selected from the group consisting of alkaline earth metal hydroxides of Formula 4 wherein M is Ca, Sr or Ba, alkali metal carbonates of Formula 4a wherein M 1 is Li, Na or K, 1,5-diazabicyclo[4.3.0]non-5-ene and 1,8-diazabicyclo[5.4.0]undec-7-ene, and an aprotic solvent capable of forming a low-boiling azeotrope with water. Also disclosed is a method for preparing a compound of Formula 2 comprising (1) forming a reaction mixture comprising a Grignard reagent derived from contacting a compound of Formula 5 wherein X is Cl, Br or I with magnesium metal or an alkylmagnesium halide in the presence of an ethereal solvent, and then (2) contacting the reaction mixture with a compound of Formula 6 wherein Y is OR 11 or NR 12 R 13 , and R 11 , R 12 and R 13 are as defined in the disclosure. Further disclosed is a method for preparing a compound of Formula 7 wherein Q and Z are as defined in the disclosure, using a compound of Formula 1 characterized by preparing the compound of Formula 1 by the method disclosed above or using a compound of Formula 1 prepared by the method disclosed above.
1. A method for preparing a compound of Formula 2
wherein
Z is phenyl optionally substituted with up to 5 substituents independently selected from R 2 ; and each R 2 is independently F, Cl, Br, C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 1 -C 6 alkoxy, C 1 -C 6 fluoroalkoxy, C 1 -C 6 alkylthio or C 1 -C 6 fluoroalkylthio;
comprising
(1) forming a reaction mixture comprising a Grignard reagent derived from a compound of Formula 5
Z—X 5
wherein X is I, by contacting the compound of Formula 5 with
(a) magnesium metal, or
(b) an alkylmagnesium halide
in the presence of an ethereal solvent; and then
(2) contacting the reaction mixture with a compound of Formula 6
wherein
Y is OR 11 or NR 12 R 13 ;
R 11 is C 1 -C 5 alkyl; and
R 12 and R 13 are independently C 1 -C 2 alkyl; or R 12 and R 13 are taken together as —CH 2 CH 2 OCH 2 CH 2 —.
2. A method for preparing a compound of Formula 2
wherein Z is
R 2a is F, Cl, Br, C 1 -C 2 fluoroalkyl or C 1 -C 2 fluoroalkoxy;
R 2b is H, F, Cl or Br; and
R 2c is H, F, Cl, Br or CF 3 ;
comprising
(1) forming a reaction mixture comprising a Grignard reagent derived from a compound of Formula 5
Z—X 5
wherein X is I, by contacting the compound of Formula 5 with
(a) magnesium metal, or
(b) an alkylmagnesium halide
in the presence of an ethereal solvent; and then
(2) contacting the reaction mixture with a compound of Formula 6
wherein
Y is OR 11 or NR 12 R 13 ;
R 11 is C 1 -C 5 alkyl; and
R 12 and R 13 are independently C 1 -C 2 alkyl; or R 12 and R 13 are taken together as —CH 2 CH 2 OCH 2 CH 2 —.
3. A compound of Formula 2
wherein
Z is
R 2a is CF 3 ;
R 2b is H or halogen; and
R 2c is halogen.
4. A compound of claim 3 selected from the group consisting of
1-[3-chloro-5-(trifluoromethyl)]-2,2,2-trifluoroethanone; and
1-[3-bromo-5-(trifluoromethyl)]-2,2,2-trifluoroethanone.
5. The method of claim 1 wherein Z is phenyl substituted with up to 5 substituents independently selected from R 2 ; and each R 2 is independently F, Cl, Br, C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 1 -C 6 alkoxy, C 1 -C 6 fluoroalkoxy, C 1 -C 6 alkylthio or C 1 -C 6 fluoroalkylthio.
6. The method of claim 1 wherein the compound of Formula 5 is contacted with magnesium metal in the presence of an ethereal solvent.
7. The method of claim 1 wherein the compound of Formula 5 is contacted with an alkylmagnesium halide in the presence of an ethereal solvent.
8. The method of claim 1 wherein Y is NR 12 R 13 .