Sulfonyl hydrazide compounds and a regio-selective process to prepare 4-aroyl pyrazole derivatives
Disclosed are compounds of Formula I, including all stereoisomers, (N-oxides), and salts thereof, wherein A and R are as defined in the disclosure. Also disclosed is a method for preparing a compound of Formula I, comprising reacting a compound of Formula II with an aroyl enolate salt of Formula III in the presence of an acid in an aqueous solvent mixture, wherein A, R and M are as defined in the disclosure. Also disclosed is a method for preparing a compound of Formula IV, comprising reacting a compound of Formula I with an aldehyde of Formula V in the presence of a secondary amine salt, wherein A, B and R are as defined in the disclosure
1. A compound selected from Formula I, N-oxides and salts thereof,
wherein
A is phenyl substituted with halogen, C 2 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylthio, C 2 -C 4 dialkylamino, cyano, nitro, C 1 -C 4 alkoxycarbonyl, phenyl or phenoxy; or
A is a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylthio, C 2 -C 4 dialkylamino, cyano, nitro, C 1 -C 4 alkoxycarbonyl, phenyl or phenoxy;R is C 1 -C 8 alkyl optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano, nitro, phenyl or phenoxy; and
R is C 1 -C 8 alkyl optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano, nitro, phenyl or phenoxy; or
R is phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano, nitro, phenyl or phenoxy.
2. The compound of claim 1 wherein
A is phenyl substituted with halogen, C 2 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy or C 1 -C 4 haloalkylthio; and
R is C 1 -C 8 alkyl optionally substituted with halogen or C 1 -C 4 alkoxy; or phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl or C 1 -C 4 haloalkoxy.
3. The compound of claim 2 wherein
A is phenyl substituted with halogen; and
R is C 1 -C 8 alkyl optionally substituted with halogen or C 1 -C 4 alkoxy; or phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy.
4. The compound of claim 1 wherein
A is phenyl substituted with halogen, C 2 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylthio, C 2 -C 4 dialkylamino, cyano, nitro, C 1 -C 4 alkoxycarbonyl, phenyl or phenoxy; and
R is C 1 -C 8 alkyl.
5. The compound of claim 4 wherein
A is phenyl substituted with halogen; and
R is CH 3 .
6. The compound of claim 3 wherein
A is phenyl substituted with halogen at 3- and 5-positions or 2- and 5-positions; and
R is phenyl optionally substituted with C 1 -C 4 alkyl.
7. The compound of claim 2 wherein
A is phenyl substituted with halogen, C 2 -C 4 alkyl and
R is 4-methylbenzene.
8. A method for preparing a compound of Formula I
wherein
A is phenyl, naphthalenyl, or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylthio, C 2 -C 4 dialkylamino, cyano, nitro, C 1 -C 4 alkoxycarbonyl, phenyl or phenoxy; and
R is C 1 -C 8 alkyl optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, haloalkyl, C 1 -C 4 haloalkoxy, cyano, nitro, phenyl or phenoxy; or
R is phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano, nitro, phenyl or phenoxy;
comprising the step of reacting a compound of Formula II
wherein
R is C 1 -C 8 alkyl optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano, nitro, phenyl or phenoxy; or
R is phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano, nitro, phenyl or phenoxy;
with an aroyl enolate salt of Formula III
wherein
M is an alkali metal or NH 4 ;
A is phenyl, naphthalenyl, or a 5- or 6- membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylthio, C 2 -C 4 dialkylamino, cyano, nitro, C 1 -C 4 alkoxycarbonyl, phenyl or phenoxy;
in the presence of an acid in an aqueous solvent mixture.
9. The method of claim 8 wherein
A is phenyl, naphthalenyl, or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy or C 1 -C 4 haloalkylthio; and
R is C 1 -C 8 alkyl optionally substituted with halogen or C 1 -C 4 alkoxy; or phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl or C 1 -C 4 haloalkoxy.
10. The method of claim 9 wherein
A is phenyl, naphthalenyl, or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen;
R is C 1 -C 8 alkyl optionally substituted with halogen or C 1 -C 4 alkoxy; or phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy;
M is an alkali metal or NH 4 ; and
the acid is a weak or moderate acid.
11. The method of claim 10 wherein
A is phenyl, 2-thienyl, 3-thienyl or 3-pyridyl, each optionally substituted with halogen or C 1 -C 4 alkyl;
R is methyl or phenyl optionally substituted with C 1 -C 4 alkyl;
M is Na or K; and
the acid is acetic acid.
12. A method for preparing a compound of Formula IV
wherein
A is phenyl, naphthalenyl, or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylthio, C 2 -C 4 dialkylamino, cyano, nitro, C 1 -C 4 alkoxycarbonyl, phenyl or phenoxy;
B is phenyl, naphthalenyl, or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylthio, C 2 -C 4 dialkylamino, cyano, nitro, C 1 -C 4 alkoxycarbonyl, phenyl or phenoxy;
comprising reacting a compound of Formula I
wherein
R is C 1 -C 8 alkyl optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano, nitro, phenyl or phenoxy; or
R is phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano, nitro, phenyl or phenoxy;
with an aldehyde of Formula V
in the presence of a secondary amine salt.
13. The method of claim 12 wherein
A is phenyl, naphthalenyl, or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy or C 1 -C 4 haloalkylthio;
R is C 1 -C 8 alkyl optionally substituted with halogen or C 1 -C 4 alkoxy; or phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl or C 1 -C 4 haloalkoxy; and
B is phenyl, naphthalenyl, or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy or C 1 -C 4 haloalkylthio.
14. The method of claim 13 wherein
A is phenyl, naphthalenyl, or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen; and
R is C 1 -C 8 alkyl optionally substituted with halogen or C 1 -C 4 alkoxy; or phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy.
15. The method of claim 14 wherein
A is phenyl, 2-thienyl, 3-thienyl or 3-pyridyl, each ring optionally substituted with halogen; and
R is methyl or phenyl optionally substituted with C 1 -C 4 alkyl.
16. The compound of claim 1 wherein
A is phenyl substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylthio, C 2 -C 4 dialkylamino, cyano, nitro, C 1 -C 4 alkoxycarbonyl, phenyl or phenoxy.
17. The compound of claim 1 wherein
A is a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylthio, C 2 -C 4 dialkylamino, cyano, nitro, C 1 -C 4 alkoxycarbonyl, phenyl or phenoxy.
18. The compound of claim 17 wherein
A is a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy or C 1 -C 4 haloalkylthio; and
R is C 1 -C 8 alkyl optionally substituted with halogen or C 1 -C 4 alkoxy; or phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl or C 1 -C 4 haloalkoxy.
19. The compound of claim 18 wherein
A is a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen; and
R is C 1 -C 8 alkyl optionally substituted with halogen or C 1 -C 4 alkoxy; or phenyl, naphthalenyl or a 5- or 6-membered heterocyclic ring, each ring or ring system optionally substituted with halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy.
20. The compound of claim 17 wherein
A is 2-thienyl, 3-thienyl or 3-pyridyl, each optionally substituted with halogen or C 1 -C 4 alkyl; and
R is 4-methylbenzene.