Continuous method for producing ortho-substituted anilines in a flow reactor

Patent metadata

Field	Value
Publication number	US-9527808-B2
Application number	US-201314427471-A
Country	US
Kind code	B2
Filing date	Sep 12, 2013
Priority date	Sep 17, 2012
Publication date	Dec 27, 2016
Grant date	Dec 27, 2016

Abstract

Continuous process for preparing ortho-substituted anilines of the formula

in a flow reactor in the presence of a nitrogen base not having an NH group, and multistage process for preparing herbicidal N-alkyl-N-[2-(1,3,5-triazin-2-ylcarbonyl)-phenyl]alkansulphonamides of the formula (4-1)

wherein the continuous process for preparing ortho-substituted anilines of the formula (4) in a flow reactor constitutes the first process step of the multistage process for preparing the herbicidal active ingredients of the formula (4-1).

First claim

The invention claimed is:

1. Process for continuously preparing a compound of formula (4)

in which
R 1 is (C 1 -C 6 ) alkyl, substituted alkyl, aryl or substituted aryl,
R 2 is an electron-withdrawing or activating substituent selected from the group consisting of
CN,
NO 2 ,
CO—R 1′ , where R 1′ is as defined for R 1 and R 1′ is the same as or different from R 1 ,
CO—X, where X is OR 1″ , SR 1″ or NR 2′ R 2″ , in which

R 1″ is as defined for R 1 and R 1″ is the same as or different from R 1 , and in which
R 2′ and R 2″ are each independently H, (C 1 -C 6 ) alkyl, substituted (C 1 -C 6 ) alkyl, aryl or substituted aryl, or R 2′ and R 2″ form a ring,
SO(n)-R 1′″ where R 1′″ is as defined for R 1 , where each R 1′″ is the same as or different from R 1 and where n is 0, 1 or 2,
aryl, and
heteroaryl,

R 3 is H, (C 1 -C 6 ) alkyl, substituted alkyl, aryl or substituted aryl,
R 4a to R 4d are each independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, CN, NO 2 , and from
(C 1 -C 6 )-alkyl, where the alkyl radical is unsubstituted or substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy and (C 3 -C 7 )-cycloalkyl,
(C 3 -C 7 )-cycloalkyl, where the cycloalkyl radical is unsubstituted or substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl and (C 3 -C 7 )-cycloalkyl and (C 1 -C 4 )-alkoxy,
(C 1 -C 6 )-alkoxy, where the alkoxy radical is unsubstituted or substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy and (C 3 -C 7 )-cycloalkyl,
(C 3 -C 7 )-cycloalkoxy, where the cycloalkoxy radical is unsubstituted or substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxy,
CO—X, where X is OR 1″ , SR 1″ or NR 2′ R 2″ , in which R 1″ is as defined for R 1 and R 1″ is the same as or different from R 1 , and in which R 2′ and R 2″ are each independently H, (C 1 -C 6 ) alkyl, substituted (C 1 -C 6 ) alkyl, aryl or substituted aryl, or R 2′ and R 2″ alternatively form a ring,
phenyl or 1-naphthyl or 2-naphthyl or a five- or six-membered heteroaromatic ring having 1 to 2 heteroatoms, where the heteroatoms are each independently selected from the group consisting of O and N, and where the aryl or heteroaryl radical is unsubstituted or substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy and (C 3 -C 7 )-cycloalkyl and (C 1 -C 4 )-alkylthio, and
R 5 is H, (C 1 -C 6 ) alkyl, substituted (C 1 -C 6 ) alkyl, aryl or substituted aryl,

in which reactants are used in a flow reactor in the presence of an organic solvent comprising
an aniline (Q)

in which
R 4 , n and R 5 are each as defined for compounds of formula (4), and
a thioether (W)

in which
R 1 , R 2 and R 3 are each as defined for compounds of formula (4),

wherein reactants of formulae (Q) and (W) are converted in the presence of
a chlorinating agent, and
at least one nitrogen base having no NH group.

2. Process for preparing a compound of formula (4) in a flow reactor according to claim 1 , wherein the reaction temperature is in a range between −65° C. and 0° C.

3. Process for preparing a compound of formula (4) in a flow reactor according to claim 2 , wherein the reaction temperature is in a range between −55° C. and −10° C. or between −45° C. and −20° C.

4. Process for preparing a compound of formula (4) in a flow reactor according to claim 1 , wherein the nitrogen base or nitrogen bases are selected from the group consisting of
tertiary amines N(R 60 ) 3 (P), in which the R 60 radicals are selected from the group of the substituted or unsubstituted C 1 -C 18 alkyl and substituted or unsubstituted (C 1 -C 6 ) aryl radicals,
cyclic tertiary amines,
substituted and unsubstituted pyridines, and
benzofused ring systems of substituted or unsubstituted pyridines.

5. Process for preparing a compound of formula (4) in a flow reactor according to claim 4 , wherein at least one of the nitrogen bases is a tertiary amine N(R 60 ) 3 (P) in which the R 60 radicals are each a substituted or unsubstituted C 1 -C 18 alkyl, where at least one of the R 60 radicals has a chain length of at least C 6 -C 18 or the R 6 radicals together have a total chain length of at least C 6 -C 18 .

6. Process for preparing a compound of formula (4) in a flow reactor according to claim 1 , wherein the nitrogen base is selected from the group consisting of
tributylamine,
2-methyl-5-ethylpyridine, and
unsubstituted quinoline.

7. Process for preparing a compound of formula (4) in a flow reactor according to claim 1 , wherein a mixture comprising at least two of the nitrogen bases selected from the group consisting of
tributylamine,
2-methyl-5-ethylpyridine and
unsubstituted quinoline

is used.

8. Process for preparing a compound of formula (4) in a flow reactor according to claim 1 , wherein the solvents used are at least one selected from the group consisting of
chloroalkanes,
aromatics,
haloaromatics, and
substituted aromatics.

9. Process for preparing a compound of formula (4) in a flow reactor according to claim 1 , wherein the chlorinating agent is selected from the group consisting of
tert-butyl hypochlorite,
sulphuryl chloride, and
a mixture of tert-butyl hypochlorite and sulphuryl chloride.

10. Process for preparing a compound of formula (4) in a flow reactor according to claim 1 , wherein at least one of the two reactants of formula (Q) and of formula (W), before addition of the chlorinating agent,
is dissolved in an organic solvent, and
is mixed with at least one nitrogen base not having an NH group and present dissolved in the selected organic solvent at a respective reaction temperature.

11. Process for preparing a compound of formula (4) in a flow reactor according to claim 1 , wherein the nitrogen base or a mixture comprising one or more nitrogen bases of which none have an NH group are supplied more than once, optionally repeatedly, to various reservoir chambers (RC) and/or mixing chambers (M) and/or dwell zones (DZ) which form part of a flow reactor.

12. Process for preparing a compound of formula (4) in a flow reactor according to claim 11 , wherein a first reservoir chamber (RC1) of the flow reactor is initially charged with a reservoir mixture 1 (RM1) at least comprising
an aniline (Q):

in which the R 4 radicals, n and R 5 radicals are each as defined in formula (4),
an organic solvent in which the aniline (Q) is dissolved, and
at least one nitrogen base not having an NH group,

and
a second reservoir chamber (RC2) of the flow reactor is initially charged with a reservoir mixture 2 (RM2) at least comprising
a liquid chlorinating agent and
an organic solvent corresponding to the solvent present in the first reservoir chamber,

and
then reservoir mixture 1 (RM1) and reservoir mixture 2 (RM2) are mixed in a first mixing cha

Assignees

• Bayer Cropscience Ag
• Bayer Technology Services Gmbh
• Bayer Ag

Inventors

• Ford Mark James
• Severins Christian

Classifications

• C07D251/20

  with no nitrogen atoms directly attached to a ring carbon atom · CPC title

• C07D209/34

  in position 2 · CPC title

• C07C319/20 Primary

  by reactions not involving the formation of sulfide groups · CPC title

• C07D251/16

  to only one ring carbon atom · CPC title

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title