US4145364A
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Preparation of fluorinated anilines
Assignee: Merck and Co Inc
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Filing: 1977-11-30
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Granted: 1979-03-20
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Expires: 1997-11-30
Abstract
Abstract Fluorinated anilines, especially p-fluoroaniline and 2,4-difluoroaniline, are prepared by treating aromatic azides with anhydrous hydrogen fluoride. The aromatic azides, in turn, are prepared from the corresponding anilines by treatment with nitrous acid or salt thereof and an alkali metal azide in the presence of a mineral acid, and in an aqueous-nonaqueous, two-phase environment.
Inventors
- 👤 Dennis M. Mulvey
- 👤 Leonard M. Weinstock
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 14:51
CPC Classifications
C; C07; C07C; C07C247/00
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
101 words
A method of preparing fluorinated anilines of structural formula: ##STR8## where R 2 , R 3 , R 5 , and R 6 may be the same or different and are independently selected from hydrogen, C 1-6 alkyl, C 1-16 alkenyl, halo, halo C 1-4 alkyl, C 1-6 alkoxy, C 1-4 alkoxycarbonyl, acyloxy, acyl, C 1-4 alkylthio, hydroxy C 1-4 alkyl, hydroxy, amino, cyano, and nitro; comprising reacting an azide compound of structural formula: ##STR9## where R 2 , R 3 , R 5 , and R 6 have the same meaning as above, with hydrogen fluoride under essentially anhydrous conditions.
Claim 2
Independent Claim
101 words
A method of preparing fluorinated anilines of structural formula: ##STR8## where R 2 , R 3 , R 5 , and R 6 may be the same or different and are independently selected from hydrogen, C 1-6 alkyl, C 1-16 alkenyl, halo, halo C 1-4 alkyl, C 1-6 alkoxy, C 1-4 alkoxycarbonyl, acyloxy, acyl, C 1-4 alkylthio, hydroxy C 1-4 alkyl, hydroxy, amino, cyano, and nitro; comprising reacting an azide compound of structural formula: ##STR9## where R 2 , R 3 , R 5 , and R 6 have the same meaning as above, with hydrogen fluoride under essentially anhydrous conditions.
Claim 3
Dependent Claim
33 words
The method of claim 1 wherein the essentially anhydrous conditions comprise an organic solvent medium wherein the solvent is selected from C 1-18 alkane, halo C 1-18 alkane, and cyclo C 1-10 alkane.
Claim 4
Dependent Claim
23 words
The method of claim 1 wherein the reaction is carried out at a temperature of from about 80° C. to about 50° C.
Claim 5
Dependent Claim
24 words
The method of claim 1 wherein the reaction is carried out over a time period of from about 1 hour to about 24 hours.
Claim 6
Dependent Claim
21 words
The method of claim 1 wherein the molar ratio of hydrogen fluoride to azide compound starting material is at least 1:1.
Claim 7
Independent Claim
15 words
A method of preparing 2,4-difluoroaniline, comprising reacting 2-fluorophenylazide with hydrogen fluoride under essentially anhydrous conditions.
Claim 8
Independent Claim
15 words
A method of preparing 2,4-difluoroaniline, comprising reacting 2-fluorophenylazide with hydrogen fluoride under essentially anhydrous conditions.
Claim 9
Dependent Claim
33 words
The method of claim 6 wherein the essentially anhydrous conditions comprise an organic solvent medium wherein the solvent is selected from C 1-18 alkane, halo C 1-18 alkane, and cyclo C 1-10 alkane.
Claim 10
Dependent Claim
23 words
The method of claim 6 wherein the reaction is carried out at a temperature of from about -80° C. to about 50° C.
Claim 11
Dependent Claim
24 words
The method of claim 6 wherein the reaction is carried out over a time period of from about 1 hour to about 24 hours.
Claim 12
Dependent Claim
18 words
The method of claim 6 wherein the molar ratio of hydrogen fluoride to 2-fluorophenylazide is at least 1:1.
Claim 13
Independent Claim
164 words
A method of preparing fluorinated anilines of structural formula: ##STR10## where R 2 , R 3 , R 5 and R 6 may be the same or different and are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkenyl, halo, halo C 1-4 alkyl, C 1-6 alkoxy, C 1-4 alkoxycarbonyl, acyloxy, acyl, C 1-4 alkylthio, hydroxy C 1-4 alkyl, hydroxy, amino, cyano, and nitro; comprising (a) reacting an aniline compound of structural formula: ##STR11## where R 2 , R 3 , R 5 and R 6 have the same meaning as above, with nitrous acid or alkali metal or alkaline earth metal salt thereof, and an alkali metal azide, in the presence of a mineral acid, in an aqueous-nonaqueous two-phase environment, to produce the corresponding azide compound of structural formula: ##STR12## where R 2 , R 3 , R 5 and R 6 have the same meaning as above; and (b) reacting said corresponding azide compound with hydrogen fluoride under essentially anhydrous conditions.
Claim 14
Independent Claim
164 words
A method of preparing fluorinated anilines of structural formula: ##STR10## where R 2 , R 3 , R 5 and R 6 may be the same or different and are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkenyl, halo, halo C 1-4 alkyl, C 1-6 alkoxy, C 1-4 alkoxycarbonyl, acyloxy, acyl, C 1-4 alkylthio, hydroxy C 1-4 alkyl, hydroxy, amino, cyano, and nitro; comprising (a) reacting an aniline compound of structural formula: ##STR11## where R 2 , R 3 , R 5 and R 6 have the same meaning as above, with nitrous acid or alkali metal or alkaline earth metal salt thereof, and an alkali metal azide, in the presence of a mineral acid, in an aqueous-nonaqueous two-phase environment, to produce the corresponding azide compound of structural formula: ##STR12## where R 2 , R 3 , R 5 and R 6 have the same meaning as above; and (b) reacting said corresponding azide compound with hydrogen fluoride under essentially anhydrous conditions.
Claim 15
Dependent Claim
26 words
The method of claim 11 wherein steps (a) and (b) are carried out as a through process without isolation of the corresponding azide compound intermediate product.
Claim 16
Dependent Claim
10 words
The method of claim 11 wherein sodium azide is employed.
Claim 17
Dependent Claim
12 words
The method of claim 11 wherein the mineral acid is hydrochloric acid.
Claim 18
Dependent Claim
27 words
The method of claim 11 wherein the nonaqueous phase comprises an organic solvent selected from C 1-18 alkane, halo C 1-18 alkane, and cyclo C 1-10 alkane.
Claim 19
Dependent Claim
23 words
The method of claim 11 wherein step (a) is carried out at a temperature of from about -5° C. to about 25° C.
Claim 20
Dependent Claim
24 words
The method of claim 11 wherein step (a) is carried out over a time period of from about 1 hour to about 10 hours.
Claim 21
Dependent Claim
25 words
The method of claim 11 wherein for step (a) the weight ratio of nonaqueous phase to aqueous phase is from about 1:2 to about 2:1.
Claim 22
Dependent Claim
36 words
The method of claim 11 wherein for step (b) the essentially anhydrous conditions comprise an organic solvent medium wherein the solvent is selected from C 1-18 alkane, halo C 1-18 alkane, and cyclo C 1-10 alkane.
Claim 23
Dependent Claim
23 words
The method of claim 11 wherein step (b) is carried out at a temperature of from about -80° C. to about 50° C.
Claim 24
Dependent Claim
24 words
The method of claim 11 wherein step (b) is carried out over a time period of from about 1 hour to about 24 hours.
Claim 25
Dependent Claim
24 words
The method of claim 11 wherein for step (b) the molar ratio of hydrogen fluoride to azide compound starting material is at least 1:1.
Claim 26
Independent Claim
62 words
A method of preparing 2,4-difluoroaniline comprising the steps of (a) reacting 2-chloronitrobenzene with potassium fluoride to form 2-fluoronitro-benzene; (b) hydrogenating the 2-fluoronitrobenzene to form 2-fluoroaniline; (c) reacting the 2-fluoroaniline with an alkali metal azide in the presence of a mineral acid and nitrous acid or salt thereof to form 2-fluorophenylazide; and (d) reacting the 2-fluorophenylazide with hydrogen fluoride under essentially anhydrous conditions.
Claim 27
Independent Claim
62 words
A method of preparing 2,4-difluoroaniline comprising the steps of (a) reacting 2-chloronitrobenzene with potassium fluoride to form 2-fluoronitro-benzene; (b) hydrogenating the 2-fluoronitrobenzene to form 2-fluoroaniline; (c) reacting the 2-fluoroaniline with an alkali metal azide in the presence of a mineral acid and nitrous acid or salt thereof to form 2-fluorophenylazide; and (d) reacting the 2-fluorophenylazide with hydrogen fluoride under essentially anhydrous conditions.
References Cited (Backward Citations)
No citation records indexed.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1982-03-19 | 1982-09-18 | 1983-03-20 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1986-03-19 | 1986-09-18 | 1987-03-20 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1990-03-19 | 1990-09-18 | 1991-03-20 | $7700.00 | Window Closed / Lapsed |