Method for preparing 3-trifluoromethyl chalcones

Patent metadata

Field	Value
Publication number	US-9527822-B2
Application number	US-201615159322-A
Country	US
Kind code	B2
Filing date	May 19, 2016
Priority date	Apr 9, 2008
Publication date	Dec 27, 2016
Grant date	Dec 27, 2016

Abstract

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.

First claim

What is claimed is:

1. A method for preparing a compound of Formula 7

wherein
Z is optionally substituted phenyl; and
Q is phenyl or 1-naphthalenyl, each optionally substituted;

using a compound of Formula 1

wherein said compound of Formula 1 is prepared by a method that comprises the steps of:
distilling water from a mixture comprising
a) a compound of Formula 2

b) a compound of Formula 3

and either
c) a base comprising at least one compound selected from the group consisting of alkaline earth metal hydroxides of Formula 4
M(OH) 2   4

wherein M is Ca, Sr or Ba,
1,5-diazabicyclo[4.3.0]non-5-ene, and
1,8-diazabicyclo[5.4.0]undec-7-ene,
and
d) an aprotic solvent capable of forming a low-boiling azeotrope with water;

or
c) a base comprising at least one compound selected from the group consisting of alkali metal carbonates of Formula 4a
(M 1 ) 2 CO 3   4a

wherein M 1 is Li, Na or K,
and
d) an aprotic solvent capable of forming a low-boiling azeotrope with water, wherein the aprotic solvent capable of forming a low-boiling azeotrope with water comprises acetonitrile.

2. The method of claim 1 wherein
Z is

 Q is

R 2a is halogen, C 1 -C 2 haloalkyl or C 1 -C 2 haloalkoxy;
R 2b is H, halogen or cyano;
R 2c is H, halogen or CF 3 ;
R 4 is H, C 2 -C 7 alkylcarbonyl or C 2 -C 7 alkoxycarbonyl; and
R 5 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl, each substituted with one substituent independently selected from hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkyl sulfonyl, C 2 -C 7 alkylaminocarbonyl, C 3 -C 9 dialkylaminocarbonyl, C 2 -C 7 haloalkylaminocarbonyl and C 3 -C 9 halodialkylaminocarbonyl.

3. The method of claim 1 wherein the base comprises an alkaline earth metal hydroxide of Formula 4 and the mixture further comprises a polar aprotic solvent.

4. The method of claim 3 wherein M is Ca.

5. The method of claim 3 wherein the polar aprotic solvent comprises N,N-dimethylformamide.

6. The method of claim 3 wherein the aprotic solvent capable of forming a low-boiling azeotrope with water comprises tert-butyl methyl ether.

7. The method of claim 1 wherein the base comprises 1,5-diazabicyclo[4.3.0]non-5-ene, 1,8-diazabicyclo[5.4.0]undec-7-ene, or a mixture thereof.

8. The method of claim 7 wherein the aprotic solvent capable of forming a low-boiling azeotrope with water comprises acetonitrile.

9. The method of claim 1 wherein the base comprises an alkali metal carbonate of Formula 4a.

10. The method of claim 9 wherein M 1 is K.

11. The method of claim 1 wherein
Z is phenyl optionally substituted with up to 5 substituents independently selected from R 2 ;
Q is phenyl or 1-naphthalenyl, each optionally substituted with up to four substituents independently selected from R 3 ;
each R 2 is independently halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylamino, C 2 -C 6 dialkylamino, —CN or —NO 2 ;
each R 3 is independently halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 3 -C 6 haloalkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 2 -C 7 alkylcarbonyl, C 2 -C 7 haloalkylcarbonyl, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, —N(R 4 )R 5 , —C(═W)N(R 4 )R 5 , —C(═W)OR 5 , —CN, —OR 11 or —NO 2 ; or a phenyl ring or a 5- or 6-membered saturated or unsaturated heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, —CN, —NO 2 , —N(R 4 )R 5 , —C(═W)N(R 4 )R 5 , —C(═O)OR 5 and R 7 ;
each R 4 is independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 alkylcycloalkyl, C 4 -C 7 cycloalkylalkyl, C 2 -C 7 alkylcarbonyl or C 2 -C 7 alkoxycarbonyl;
each R 5 is independently H; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 alkylcycloalkyl or C 4 -C 7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R 6 ;
each R 6 is independently halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino, C 2 -C 8 dialkylamino, C 3 -C 6 cycloalkylamino, C 2 -C 7 alkylcarbonyl, C 2 -C 7 alkoxycarbonyl, C 2 -C 7 alkylaminocarbonyl, C 3 -C 9 dialkylaminocarbonyl, C 2 -C 7 haloalkylcarbonyl, C 2 -C 7 haloalkoxycarbonyl, C 2 -C 7 haloalkylaminocarbonyl, C 3 -C 9 halodialkylaminocarbonyl, —OH, —NH 2 , —CN or —NO 2 ; or Q 1 ;
each R 7 is independently a phenyl ring or a pyridinyl ring, each ring optionally substituted with one or more substituents independently selected from R 8 ;
each R 8 is independently halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, C 1 -C 6 alkylamino, C 2 -C 6 dialkylamino, C 2 -C 4 alkylcarbonyl, C 2 -C 4 alkoxycarbonyl, C 2 -C 7 alkylaminocarbonyl, C 3 -C 7 dialkylaminocarbonyl, —OH, —NH 2 , —C(═O)OH, —CN or —NO 2 ;
each Q 1 is independently a phenyl ring or a 5- or 6-membered saturated or unsaturated heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, C 1 -C 6 alkylamino, C 2 -C 6 dialkylamino, —CN, —NO 2 , —C(═W)N(R 9 )R 10 and —C(═O)OR 10 ;
each R 9 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 alkylcycloalkyl, C 4 -C 7 cycloalkylalkyl, C 2 -C 7 alkylcarbonyl or C 2 -C 7 alkoxycarbonyl;
each R 10 is independently H; or C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 alkylcycloalkyl or C 4 -C 7 cycloalkylalkyl;
each R 11 is independently H; or C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 alkylcycloalkyl, C 4 -C 7 cycloalkylalkyl, C 2 -C 7 alkylcarbonyl, C 2 -C 7 alkoxycarbonyl, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl; and
each W is independently O or S.

Assignees

• Du Pont

Inventors

• Annis Gary David

Classifications

• C07C49/80

  containing halogen · CPC title

• C07D261/04 Primary

  having one double bond between ring members or between a ring member and a non-ring member · CPC title

• C07C45/74

  combined with dehydration · CPC title

• C07C209/74

  by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title