IP Library › Granted Patent US 8,053,572

Granted Patent B2

US 8,053,572 · App. 11/817,373 · Granted Nov 8, 2011

Alkyl-analide producing method

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Quick Facts

Patent No.: US 8,053,572
App. No.: 11/817,373
Granted: Nov 8, 2011
Kind: B2

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Abstract

The present invention relates to a process for preparing known fungicidally effective alkylanilides from acid chlorides and aminoacetophenone via hydroxyalkyl-substituted carboxanilides, alkenylanilides and benzoxazine derivatives.

Claims (223)

1. A process for preparing alkylanilides of the formula (I)

in which

R 1 represents hydrogen or fluorine,

R 2 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 9 fluorine, chlorine or bromine atoms;

A represents the radical of the formula (A1)

in which

R 3 represents hydrogen, cyano, halogen, nitro, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 3 -C 6 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy or C 1 -C 4 -haloalkylthio having in each case 1 to 5 halogen atoms, aminocarbonyl or aminocarbonyl-C 1 -C 4 -alkyl,

R 4 represents hydrogen, halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy or C 1 -C 4 -alkylthio, and

R 5 represents hydrogen, C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 2 -C 6 -alkenyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkylthio-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkylthio-C 1 -C 4 -alkyl, C 1 -C 4 -haloalkoxy-C 1 -C 4 -alkyl having in each case 1 to 5 halogen atoms, or phenyl,

A represents the radical of the formula (A2)

in which

R 6 and R 7 independently of one another represent hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 8 represents halogen, cyano, C 1 -C 4 -alkyl, or C 1 -C 4 -haloalkyl or C 1 -C 4 -haloalkoxy having in each case 1 to 5 halogen atoms,

A represents the radical of the formula (A3)

in which

R 9 and R 10 independently of one another represent hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 11 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A4)

in which

R 12 represents hydrogen, halogen, hydroxyl, cyano, C 1 -C 6 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy or C 1 -C 4 -haloalkylthio having in each case 1 to 5 halogen atoms,

A represents the radical of the formula (A5)

in which

R 13 represents halogen, hydroxyl, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkylthio or C 1 -C 4 -haloalkoxy having in each case 1 to 5 halogen atoms, and

R 14 represents hydrogen, halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy having in each case 1 to 5 halogen atoms, C 1 -C 4 -alkylsulfinyl or C 1 -C 4 -alkylsulfonyl,

A represents the radical of the formula (A6)

in which

R 15 represents C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

R 16 represents C 1 -C 4 -alkyl,

Q 1 represents S (sulphur), O (oxygen), SO, SO 2 or CH 2 , and

p represents 0, 1 or 2, where R 16 represents identical or different radicals if p represents 2,

A represents the radical of the formula (A7)

in which

R 17 represents C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A8)

in which

R 18 represents C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A9)

in which

R 19 and R 20 independently of one another represent hydrogen, halogen, amino, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 21 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A10)

in which

R 22 and R 23 independently of one another represent hydrogen, halogen, amino, nitro, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 24 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A11)

in which

R 25 represents hydrogen, halogen, amino, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, cyano, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 26 represents halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A12)

in which

R 27 represents hydrogen, halogen, amino, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, cyano, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 28 represents halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A13)

in which

R 29 represents halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A14)

in which

R 30 represents hydrogen or C 1 -C 4 -alkyl, and

R 31 represents halogen or C 1 -C 4 -alkyl,

A represents the radical of the formula (A15)

in which

R 32 represents C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A16)

in which

R 33 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A17)

in which

R 34 represents halogen, hydroxyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkylthio or C 1 -C 4 -haloalkoxy having in each case 1 to 5 halogen atoms,

A represents the radical of the formula (A18)

in which

R 35 represents hydrogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 4 -alkylsulfonyl, di(C 1 -C 4 -alkyl)aminosulfonyl, C 1 -C 6 -alkylcarbonyl or in each case optionally substituted phenylsulfonyl or benzoyl,

R 36 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

R 37 represents hydrogen, halogen, cyano, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 38 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A19)

in which

R 39 represents C 1 -C 4 -alkyl,

comprising:

a) reacting a carbonyl halide of the formula (II)

in which

A is a radical of formulae (A1), (A2), (A3), (A4), (A5), (A6), (A7), (A8), (A9), (A10), (A11), (A12), (A13), (A14), (A15), (A16), (A17), (A18), or (A19) defined above, and

Hal 1 represents fluorine, chlorine or bromine,

with an acetophenone derivative of the formula (III) or a salt thereof

in which R 1 is hydrogen or fluorine,

optionally in the presence of an acid binder and optionally in the presence of a diluent,

to give

an acetylanilide of the formula (IV)

in which A and R 1 are as defined above,

b) reacting a compound of formula (IV) with a Grignard reagent of the formula (V)

in which

R 2 is hydrogen, halogen, C 1 -C 4 -aklyl or C 1 -C 4 -haloalkyl having 1 to 9 fluorine, chlorine or bromine atoms, and

Hal 2 represents chlorine, bromine or iodine,

in the presence of a diluent,

to give

a hydroxyalkylcarboxanilide of the formula (VI)

in which R 1 , R 2 and A are as defined above, and

c1) hydrogenating a compound of formula (VI) in the presence of a catalyst and in the presence of a diluent and an acid, to give a compound of formula (I);

c2) reacting a compound of formula (VI) in the presence of an acid and in the presence of a diluent,

to give a benzoxazine of the formula (VIIa) and an alkenylanilide of the formulae (VIIb) and (VIIc)

in which R 1 , R 2 and A are as defined above, and

d) hydrogenating a compound of formula (VIIa), (VIIb), or (VIIc) in the presence of a catalyst, optionally in the presence of an acid and in the presence of a diluent, to give a compound of formula (I).

2. The process of claim 1 , wherein b) is carried out in toluene, toluene/tetrahydrofuran mixtures or toluene/methyl tert-butyl ether mixtures.

3. The process of claim 1 , wherein in b) the solvent is initially charged and during the reaction a compound of formula (IV) and a compound of formula (V) are metered in simultaneously.

4. The process of claim 1 , wherein said compound of formula (II) is 1,3-dimethyl-5-fluoro-4-pyrazolcarbonyl chloride or 1,3-dimethyl-5-fluoro-4-pyrazolcarbonyl fluoride, said compound of formula (III) is 2-aminoacetophenone and said compound of formula (V) is isobutylmagnesium chloride and the product obtained is N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazol-4-carboxamide.

5. A compound of formula (VIIa)

in which

R 1 represents hydrogen or fluorine,

R 2 represents hydrogen, halogen, C 1 -C 4 -aklyl or C 1 -C 4 -haloalkyl having 1 to 9 fluorine, chlorine or bromine atoms;

A represents the radical of the formula (A1)

in which

R 4 represents hydrogen, halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy or C 1 -C 4 -alkylthio, and

A represents the radical of the formula (A2)

in which

R 6 and R 7 independently of one another represent hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 8 represents halogen, cyano, C 1 -C 4 -alkyl, or C 1 -C 4 -haloalkyl or C 1 -C 4 -haloalkoxy having in each case 1 to 5 halogen atoms,

A represents the radical of the formula (A3)

in which

R 9 and R 10 independently of one another represent hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 11 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A4)

in which

R 12 represents hydrogen, halogen, hydroxyl, cyano, C 1 -C 6 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy or C 1 -C 4 -haloalkylthio having in each case 1 to 5 halogen atoms,

A represents the radical of the formula (A5)

in which

A represents the radical of the formula (A6)

in which

R 15 represents C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

R 16 represents C 1 -C 4 -alkyl,

Q 1 represents S (sulphur), O (oxygen), SO, SO 2 or CH 2 , and

p represents 0, 1 or 2, where R 16 represents identical or different radicals if p represents 2,

A represents the radical of the formula (A7)

in which

R 17 represents C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A8)

in which

R 18 represents C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A9)

in which

R 19 and R 20 independently of one another represent hydrogen, halogen, amino, C 1 -C 4 -alkyl or C 1 -C 1 -haloalkyl having 1 to 5 halogen atoms, and

R 21 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A10)

in which

R 22 and R 23 independently of one another represent hydrogen, halogen, amino, nitro, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 24 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A11)

in which

R 25 represents hydrogen, halogen, amino, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, cyano, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 26 represents halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A12)

in which

R 27 represents hydrogen, halogen, amino, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, cyano, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 28 represents halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A13)

in which

R 29 represents halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A14)

in which

R 30 represents hydrogen or C 1 -C 4 -alkyl, and

R 31 represents halogen or C 1 -C 4 -alkyl,

A represents the radical of the formula (A15)

in which

R 32 represents C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A16)

in which

R 33 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A17)

in which

A represents the radical of the formula (A18)

in which

R 36 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

R 37 represents hydrogen, halogen, cyano, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms, and

R 38 represents hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl having 1 to 5 halogen atoms,

A represents the radical of the formula (A19)

in which

R 39 represents C 1 -C 4 -alkyl.

6. The process of claim 2 , wherein in b) the solvent is initially charged and during the reaction a compound of formula (IV), preferably in solid form, and a compound of formula (V) are metered in simultaneously.

7. The process of claim 2 , wherein said compound of formula (II) is 1,3-dimethyl-5-fluoro-4-pyrazolcarbonyl chloride or 1,3-dimethyl-5-fluoro-4-pyrazolcarbonyl fluoride, said compound of formula (III) is 2-aminoacetophenone, and said compound of formula (V) is isobutylmagnesium chloride, and the product obtained is N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazol-4-carboxamide.

8. The process of claim 3 , wherein said compound of formula (II) is 1,3-dimethyl-5-fluoro-4-pyrazolcarbonyl chloride or 1,3-dimethyl-5-fluoro-4-pyrazolcarbonyl fluoride, said compound of formula (III) is 2-aminoacetophenone, and said compound of formula (V) is isobutylmagnesium chloride, and the product obtained is N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazol-4-carboxamide.

9. The process of claim 6 , wherein said compound of formula (II) is 1,3-dimethyl-5-fluoro-4-pyrazolcarbonyl chloride or 1,3-dimethyl-5-fluoro-4-pyrazolcarbonyl fluoride, said compound of formula (III) is 2-aminoacetophenone, and said compound of formula (V) is isobutylmagnesium chloride, and the product obtained is N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazol-4-carboxamide.

10. The process of claim 3 , wherein said compound of formula (IV) is in solid form.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 23, 2015

From: BAYER CROPSCIENCE AG

To: BAYER INTELLECTUAL PROPERTY GMBH

Reel/Frame 035005/0367 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 27, 2008

From: STRAUB, ALEXANDER

To: BAYER CROPSCIENCE AG

Reel/Frame 021445/0917 →