WO1993003002A1 - Production of fluoro-aromatic amines - Google Patents

Production of fluoro-aromatic amines Download PDF

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Publication number
WO1993003002A1
WO1993003002A1 PCT/US1992/005994 US9205994W WO9303002A1 WO 1993003002 A1 WO1993003002 A1 WO 1993003002A1 US 9205994 W US9205994 W US 9205994W WO 9303002 A1 WO9303002 A1 WO 9303002A1
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Prior art keywords
formula
ring position
compound
carbon atoms
alkyl group
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Application number
PCT/US1992/005994
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French (fr)
Inventor
Ali A. Bazzi
Ervin B. Inskip
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Mallinckrodt Specialty Chemicals Company
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Publication date
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Publication of WO1993003002A1 publication Critical patent/WO1993003002A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
    • C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
    • C07C209/10—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to carbon atoms of six-membered aromatic rings or from amines having nitrogen atoms bound to carbon atoms of six-membered aromatic rings

Definitions

  • the present invention relates to a process for producing fluoro-aromatic amines.
  • it relates to a process for direct amination of
  • fluoro- aromatic amines such as fluoroaniline
  • fluoroaniline involves nitration of fluorobenzene, followed by reduction of the resulting fluoronitrobenzene isomers to the corresponding anilines.
  • this method suffers from drawbacks in that separation of p-fluoroaniline and o-fluoroaniline is difficult because of their close boiling points.
  • p-nitrofluorobenzene is formed from p- nitrochlorobenzene.
  • the p-nitrofluorobenzene then is reduced to form p-fluoroaniline.
  • This process requires high temperatures and the use of a high boiling point solvent, such as dimethyl sulfoxide, which has rendered this process expensive.
  • US 4,508,922 (Ratton; Rhone-Poulenc; 1985) teaches a process for producing optionally halogenated anilines by subjecting halogenated benzenes to ammonolysis with aqueous ammonia solution in the presence of copper and 8- hydroxyquinoline.
  • a process for producing fluoro-aramatic amines comprises providing a compound of the formula (I)
  • -NR 5 R 6 has a ring position in formula (II) which corresponds to the ring position of Br in formula (I);
  • R 1 , R 2 , R 3 and R 4 are as defined above; and
  • R 5 and R 6 may be the same or different, and represent H or an alkyl group of from 1 to about 10 carbon atoms.
  • the inventive process utilizes as a starting
  • R 5 and R 6 may be the same or different, and represent H or an alkyl group of from 1 to about 10 carbon atoms, which may be straight chain or branched.
  • R 1 , R 2 , R 3 , and R 4 represent H or an alkyl group of from 1 to about 5 carbon atoms, more preferably H or an alkyl group of from 1 to about 3 carbon atoms.
  • R 1 , R 2 , R 3 , and R 4 are H.
  • Br has a ring position in formula (I) which is para to F, and the R 6 and R 6 groups are H.
  • Br has a ring position in formula (I) which is para to F, and the R 5 group is H while R 6 is methyl.
  • the present invention provides for direct amination of unsubstituted or alkyl-substituted
  • bromofluorobenzenes When such bromofluorobenzenes are reacted with amines of the formula NHR 5 R 6 , in the presence of cuprous oxide, only the corresponding amino compounds appear to be formed. This selective amination route of p-, o- and m- bromofluorobenzenes results in yields of greater than 90% of the corresponding anilines.
  • p-fluoroaniline For the production of p-fluoroaniline, one-litre parr bomb was charged with 364 g (2.1 mole) p- bromofluorobenzene, 450 ml of 27% aqueous ammonia and 3.5 g of cuprous oxide. The mixture was heated to 200°C at 475 psi for 6 hours, after which the pressure dropped to about 380 psi. After cooling to room temperature, the resulting greenish liquid was transferred to a separatory funnel and the organic layer separated and filtered.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

In a process for producing fluoro-aromatic amines, the starting material is a compound of formula (I) wherein Br has a ring position which is ortho, meta or para to F, and R1, R2, R3 and R4 can be the same or different, and represent H or an alkyl group of from 1 to about 10 carbon atoms. The compound of formula (I) is reacted with an amine of the formula NHR5R6 in the presence of cuprous oxide so as to form a compound of formula (II) wherein -NH5R6 has a ring position in formula (II) which corresponds to the ring position of Br in formula (I); R1, R2, R3 and R4 are as defined above; and R5 and R6 may be the same or different, and represent H or an alkyl group of from 1 to about 10 carbon atoms.

Description

PRODUCTION OF FLUORO-AROMATIC AMINES
BACKGROUND OF THE INVENTION
Field of the Invention
The present invention relates to a process for producing fluoro-aromatic amines. In particular, it relates to a process for direct amination of
unsubstituted or alkyl-substituted bromofluorobenzenes.
Description of the Background Art
There are several known methods for making fluoro- aromatic amines such as fluoroaniline. For example, one method for making fluoroaniline involves nitration of fluorobenzene, followed by reduction of the resulting fluoronitrobenzene isomers to the corresponding anilines. However, this method suffers from drawbacks in that separation of p-fluoroaniline and o-fluoroaniline is difficult because of their close boiling points.
In another known method for producing p- fluoroaniline, p-nitrofluorobenzene is formed from p- nitrochlorobenzene. The p-nitrofluorobenzene then is reduced to form p-fluoroaniline. This process requires high temperatures and the use of a high boiling point solvent, such as dimethyl sulfoxide, which has rendered this process expensive. US 4,508,922 (Ratton; Rhone-Poulenc; 1985) teaches a process for producing optionally halogenated anilines by subjecting halogenated benzenes to ammonolysis with aqueous ammonia solution in the presence of copper and 8- hydroxyquinoline.
Paine, Mechanisms and Models for Copper Mediated Nucleophilic Aromatic Substitution, J. Am. Chem. Soc., 1987, 109, p. 1496-1502, teaches the use of various copper-based catalysts with aryl or diaryl amine
reactants.
There remains a need in the art for simple and inexpensive methods for producing high yields of desired p-, o- or m- fluoroaromatic amines. Summary of the Invention
In accordance with the present invention, a process for producing fluoro-aramatic amines comprises providing a compound of the formula (I)
Figure imgf000004_0001
wherein Br has a ring position which is ortho, meta or para to F, and R1, R2, R3 and R4 can be the same or
different, and represent H or an alkyl group of from 1 to about 10 carbon atoms. The compound of formula (I) is reacted with an amine of the formula NHR5R6 in the presence of cuprous oxide so as to form a compound of the formula (II)
Figure imgf000005_0001
wherein -NR5R6 has a ring position in formula (II) which corresponds to the ring position of Br in formula (I); R1, R2, R3 and R4 are as defined above; and R5 and R6 may be the same or different, and represent H or an alkyl group of from 1 to about 10 carbon atoms.
Detailed Description of the Preferred Embodiments
The inventive process utilizes as a starting
material a compound of the formula (I) set forth above, wherein Br has a ring position which is ortho, meta or para to F, and R1, R2, R3 and R4 can be the same or
different and represent H or an alkyl group of from l to about 10 carbon atoms, which may be straight chain or branched.
The compound of formula (I) set forth above is reacted with an amine of the formula NHR5R6 in the
presence of cuprous oxide so as to form a compound of the formula (II) set forth above, wherein -NR5R6 has a ring position in formula (II) which corresponds to the ring position of Br in formula (I). R5 and R6, like R1, R2, R3 and R4, may be the same or different, and represent H or an alkyl group of from 1 to about 10 carbon atoms, which may be straight chain or branched.
In preferred embodiments, R1, R2, R3, and R4 represent H or an alkyl group of from 1 to about 5 carbon atoms, more preferably H or an alkyl group of from 1 to about 3 carbon atoms.
In particularly preferred embodiments, R1, R2, R3, and R4 are H.
In embodiments wherein Br has a ring position in formula (I) which is ortho or meta to F, R5 and R6
preferably are H.
In accordance with one embodiment, Br has a ring position in formula (I) which is para to F, and the R6 and R6 groups are H. In another embodiment, Br has a ring position in formula (I) which is para to F, and the R5 group is H while R6 is methyl. In still another
embodiment wherein Br has a ring position in formula (I) which is para to F, the R5 group is H and R6 is isopropyl.
The bromofluorobenzene starting compound, the amine and the cuprous oxide are reacted at sufficient
temperature (e.g., about 150-255°C) and pressure (e.g., about 425-525 psi), over a long enough period of time (e.g., about 3-9 hours), to cause substitution of the amine group for the bromine of the starting compound.
Thereafter, the desired product can be separated,
filtered and recovered by any suitable means. The present invention provides for direct amination of unsubstituted or alkyl-substituted
bromofluorobenzenes. When such bromofluorobenzenes are reacted with amines of the formula NHR5R6, in the presence of cuprous oxide, only the corresponding amino compounds appear to be formed. This selective amination route of p-, o- and m- bromofluorobenzenes results in yields of greater than 90% of the corresponding anilines.
The invention is further illustrated by the
following examples, which are not intended to be
limiting.
Example I
For the production of p-fluoroaniline, one-litre parr bomb was charged with 364 g (2.1 mole) p- bromofluorobenzene, 450 ml of 27% aqueous ammonia and 3.5 g of cuprous oxide. The mixture was heated to 200°C at 475 psi for 6 hours, after which the pressure dropped to about 380 psi. After cooling to room temperature, the resulting greenish liquid was transferred to a separatory funnel and the organic layer separated and filtered.
Vacuum distillation afforded the colorless product in 91% yield. The product was identified as p-fluoroaniline on the basis of IR, 1H and 13C NMR analyses. Example II
Using substantially similar procedures as set forth in the Example I, o-fluoroaniline was prepared in 90%+ yield from the corresponding o-bromofluorobenzene.
Example III
In a substantially similar process as is set forth in example I, m-fluoroaniline was prepared in 90%+ yield from corresponding m-bromofluorobenzene.
Since many modifications, variations and changes in detail may be made to the described embodiments, it is intended that all matter in the foregoing description be interpreted as illustrative and not in a limiting sense.

Claims

Claims
1. A process for producing fluoro-aromatic amines, comprising:
a) providing a compound of formula (I)
Figure imgf000009_0001
wherein Br has a ring position which is ortho, meta, or para to F, and R3, R2, R3 and R4 are the same or different and represent H or an alkyl group of from 1 to about 10 carbon atoms, and
b) reacting a compound of formula (I) with an amine of the formula NHR5R6 in the presence of cuprous oxide so as to form a compound of the formula (II)
Figure imgf000009_0002
wherein -NR5R6 has a ring position in formula (II) which corresponds to the ring position of Br in formula (I); R1 R2, R3 and R4 are as defined above; and
R5 and R6 are the same or different and represent H or an alkyl group of from 1 to about 10 carbon atoms.
2. The process of claim 1 wherein R1, R2, R3, R4, R5, and R6 are the same or different, and represent H or an alkyl group of from 1 to about 5 carbon atoms.
3. The process of claim 2 wherein R1, R2, R3, R4, R5, and R6 are the same or different, and represent H or an alkyl group of from 1 to about 3 carbon atoms.
4. The process of claim 3 wherein R1, R2, R3 and R4 are H.
5. The process of claim 4 wherein Br has a ring position which is ortho to F.
6. The process of claim 5 wherein R5 and R6 are H.
7. The process of claim 4 wherein Br has a ring position which is meta to F.
8. The process of claim 7 wherein R5 and R6 are H.
9. The process of claim 4 wherein Br has a ring position which is para to F.
10. The process of claim 9 wherein R5 and R6 are H.
11. The process of claim 9 wherein R5 is H and R6 is methyl.
12. The process of claim 9 wherein R5 is H and R6 is isopropyl.
PCT/US1992/005994 1991-08-06 1992-07-17 Production of fluoro-aromatic amines WO1993003002A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US74263991A 1991-08-06 1991-08-06
US742,639 1991-08-06

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2389596A1 (en) * 1977-05-06 1978-12-01 Basf Ag
EP0098783A1 (en) * 1982-06-29 1984-01-18 Rhone-Poulenc Agrochimie Process for the preparation of halogen anilines

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2389596A1 (en) * 1977-05-06 1978-12-01 Basf Ag
EP0098783A1 (en) * 1982-06-29 1984-01-18 Rhone-Poulenc Agrochimie Process for the preparation of halogen anilines

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