Malonic acid di-salts and a method for preparing malonyl dihalides

1. A compound of Formula 2

wherein

R 1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R 2 ;

each R 2 is independently halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy or C 1 -C 4 haloalkoxy;

Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C 1 -C 4 haloalkyl; and

each M A and M B is independently Li, Na, K, NH 4 , NH(CH 2 CH 3 ) 3 , NH(CH 2 CH 2 CH 2 CH 3 ) 3 , NH 2 (Bn) 2 , NH 2 (cyclohexyl) 2 or NH 2 (phenyl) 2 .

2. A compound of claim 1 wherein

R 1 is phenyl optionally substituted with up to 2 substituents independently selected from R 2 ;

each R 2 is independently halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy or C 1 -C 2 haloalkoxy; and

each M A and M B is independently Na, K, NH 4 or NH(CH 2 CH 3 ) 3 .

3. A compound of claim 2 wherein

R 1 is phenyl substituted with 2 substituents selected from R 2 at the 3- and 5-positions;

each R 2 is independently Cl or —CF 3 ; and

each M A and M B is independently Na, K or NH 4 .

4. A compound of claim 2 wherein

R 1 is phenyl substituted with 1 substituent selected from R 2 at the 3-position;

each R 2 is independently —CF 3 or —OCF 3 ; and

each M A and M B is independently Na, K or NH 4 .

5. A method for preparing a compound of Formula 1

wherein

R 1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R 2 ;

each R 2 is independently halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy or C 1 -C 4 haloalkoxy;

Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C 1 -C 4 haloalkyl; and

X is Cl or Br

comprising contacting a compound of Formula 2

wherein

R 1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R 2 ;

each R 2 is independently halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy or C 1 -C 4 haloalkoxy;

Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C 1 -C 4 haloalkyl; and

each M A and M B is independently Li, Na, K, NH 4 , NH(CH 2 CH 3 ) 3 , NH(CH 2 CH 2 CH 2 CH 3 ) 3 , NH 2 (Bn) 2 , NH 2 (cyclohexyl) 2 or NH 2 (phenyl) 2 ,

with a halogenating agent,

wherein the halogenating agent is oxalyl chloride, thionyl chloride, phosgene, triphosgene, cyanuric chloride, phosphorous oxychloride, phosphorous trichloride, phosphorous pentachloride, diphosgene, sulfuryl chloride, thionyl bromide, triphenylphosphine dibromide or phosphorous tribromide.

6. The method of claim 5 wherein

R 1 is phenyl optionally substituted with up to 2 substituents independently selected from R 2 ;

each R 2 is independently halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy or C 1 -C 2 haloalkoxy; and

each M A and M B independently Na, K, NH 4 , NH(CH 2 CH 3 ) 3 or NH(C 2 CH 2 CH 2 CH 3 ) 3 .

7. The method of claim 5 wherein the halogenating agent is oxalyl chloride, thionyl chloride, phosgene, triphosgene or cyanuric chloride; and

X is Cl.

8. A method of preparing a compound of Formula 4

wherein

R 1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R 2 ;

each R 2 is independently halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxv or C 1 -C 4 haloalkoxy;

Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C 1 -C 4 haloalkyl;

R 3 is thiazolyl or pyrimidinyl, each optionally substituted with halogen or C 1 -C 2 alkyl; and

R 4 is H or C 1 -C 4 alkyl;

comprising preparing a compound of Formula 1

wherein

R 1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R 2 ;

each R 2 is independently halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy or C 1 -C 4 haloalkoxy;

Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C 1 -C 4 haloalkyl; and

X is Cl or Br

by contacting a compound of Formula 2

wherein

R 1 is phenyl optionally substituted with Q and up to 3 substituents independently selected from R 2 ;

each R 2 is independently halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy or C 1 -C 4 haloalkoxy;

Q is pyridinyl optionally substituted with up to 2 substituents independently selected from halogen and C 1 -C 4 haloalkyl; and

each M A and M B is independently Li, Na, K, NH 4 , NH(CH 2 CH 3 ) 3 , NH(CH 2 CH 2 CH 2 CH 3 ) 3 , NH 2 (Bn) 2 , NH 2 (cyclohexyl) 2 or NH 2 (phenyl) 2 ;

with a halogenating agent

wherein the halogenating agent is oxalyl chloride, thionyl chloride, phosgene, triphosgene, cyanuric chloride, phosphorous oxychloride, phosphorous trichloride, phosphorous pentachloride, diphosgene, sulfuryl chloride, thionyl bromide, triphenylphosphine dibromide or phosphorous tribromide;

to produce a compound of Formula 1; and

reacting a compound of Formula 5

wherein

R 3 is thiazolyl or pyrimidinyl, each optionally substituted with halogen or C 1 -C 2 alkyl; and

R 4 is H or C 1 -C 4 alkyl;

with the compound of Formula 1 to prepare the compound of Formula 4.

9. The method of claim 8 wherein

R 1 is phenyl optionally substituted with up to 2 substituents independently selected from R 2 ;

each R 2 is independently Cl or —CF 3 ;

R 3 is 2-chloro-5-thiazolyl;

R 4 is CH 3 ; and

each M A and M B is independently Na, K, NH 4 , NH(CH 2 CH 3 ) 3 .

10. The method of claim 8 wherein

R 1 is phenyl substituted with 1 substituent selected from R 2 ;

each R 2 is independently —CF 3 or —OCF 3 ;

R 3 is 5-pyrimidinyl; and

R 4 is H; and

each M A and M B is independently Na, K or NH 4 .

11. The method of claim 5 wherein the contacting is performed in an aprotic organic solvent.

12. The method of claim 11 wherein the aprotic organic solvent is toluene, dichloromethane, cyclohexane, benzene, 1,2-dichloroethane, ethyl acetate, butyl acetate or a combination of any of the foregoing.

13. The method of claim 5 wherein the contacting is performed in the presence of pyridine or a compound of Formula 3

wherein

R E is C 1 -C 4 alkyl;

R F is C 1 -C 4 alkyl; or

R E and R F are taken together as C 4 -C 6 alkylene.