Granted Patent B2

US 10,160,731 · App. 15/946,601 · Granted Dec 25, 2018

Inventor: Gary David Annis (Landenberg, PA)

Assignee: E.I. du Pont de Nemours and Company

C07D261/04C07C17/35C07C25/13C07C45/455C07C45/70C07C49/80C07C49/813C07C67/343C07C205/45C07C209/74C07C231/12C07C231/14C07C235/84C07D213/40C07D231/12C07D231/14C07D231/16C07D249/08C07D249/10C07D277/28

Abstract

Claims (58)

1. A method for preparing a compound of Formula 1

wherein,

Z is optionally substituted phenyl; and

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

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

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;

wherein the aprotic solvent capable of forming a low-boiling azeotrope with water comprises acetonitrile.

2. The method of claim 1 wherein the base comprises 1,5-diazabicyclo[4.3.0]non-5-ene.

3. 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 2 -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 alkysulfinyl, 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.

4. The method of claim 3 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 3 is C(O)N(R 4 )R 5 or C(O)OR 5a ;

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 alkylsulfonyl, C 2 -C 7 alkylaminocarbonyl, C 3 -C 9 dialkylaminocarbonyl, C 2 -C 7 haloalkylaminocarbonyl and C 3 -C 9 halodialkylaminocarbonyl; and

R 5a is C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each optionally substituted with one or more substituents independently selected from halogen, C 1 -C 2 alkoxy and phenyl optionally substituted with up to 5 substituents selected from halogen and C 1 -C 3 alkyl.

5. The method of claim 1 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;

further comprising preparing the compound of Formula 2 by

(1) forming a reaction mixture comprising a Grignard reagent derived from a compound of Formula 5

Z—X   5

wherein X is Cl, Br or 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 —.

6. The method of claim 5 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 .

7. The method of claim 1 wherein the base comprises 1,8-diazabicyclo[5.4.0]undec-7-ene.

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

Assignments (2)

Continuity (8)