GB2183667A - Synthesis of naphthalimide derivatives - Google Patents
Synthesis of naphthalimide derivatives Download PDFInfo
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- GB2183667A GB2183667A GB08526587A GB8526587A GB2183667A GB 2183667 A GB2183667 A GB 2183667A GB 08526587 A GB08526587 A GB 08526587A GB 8526587 A GB8526587 A GB 8526587A GB 2183667 A GB2183667 A GB 2183667A
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- Prior art keywords
- naphthylimide
- amine
- halo
- methyl pyrrolidone
- reacting
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/14—Aza-phenalenes, e.g. 1,8-naphthalimide
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B57/00—Other synthetic dyes of known constitution
- C09B57/08—Naphthalimide dyes; Phthalimide dyes
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- Organic Chemistry (AREA)
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Abstract
2- or 4-Aminonaphthalimides are prepared from 2- or 4-halonaphthalimide or 2- or 4-halonaphthalic anhydride by reaction with an amine in N-methylpyrrolidone. Preferred products are 4-alkylamino-N-alkylnaphthalimides useful as fluorescent dyes. 2- or 4-Alkoxynaphthalimides are prepared from 2- or 4-halonaphthalimides by reaction with alkali metal alkoxide in N-methylpyrrolidone. 2- or 4-Halonaphthalimides are prepared from 2- or 4-halonaphthalic anhydrides by reaction with a primary amine in ethanol.
Description
SPECIFICATION
Preparation of amino-1,8-naphthylimides
This invention relates to the preparation of amino-l ,8-naphthylimides, and finds particular application in the preparation of 4-alkylamino-N-alkyl-1 ,8-naphthylimides. These last compounds are useful as fluorescent dyes, for example in the non-destructive testing of metal surfaces.
A number of synthetic routes for the preparation of 4-alkylamino-N-alkyl-1,8-naphthylimides exist, for example, those disclosed in US 2 385 106 and US 2415373. Both these US patents disclose the preparation of 4-alkylamino-N-alkyl-1 ,8-naphthylimides by reacting either the 4-bromo or 4-chloro-1 ,8-naphthalic anhydride with an amine in an inert diluent to produce the 4-bromo or 4-chloro-N-alkyl-1 ,8-naphthylimide, and subsequent reaction of the naphthylimide with another or the same amine in an inert diluent to produce the 4-alkylamino-N-alkyl-1 ,8-naphthylimide.
EP 0 010 994 discloses a similar reaction, but in this case the starting material is 4-nitro-1 ,8-naphthalic anhydride.
Ali these prior art preparations suffer from the disadvantage that the product is a tarry mixture which requires extensive chromatographic purification to obtain the pure product Consequently, these processes are expensive and time consuming. The present inventors have devised a novel preparative route for amino-i ,8-naphthylimides, the product of which requires only a simple recrystallisation to provide a high purity amino-1,8-naphthylimide.
According to the present invention there is provided a method of preparing an amino-1,8-naphthylimide, comprising: (a) reacting a halo-i ,8-naphthalic anhydride with a primary amine A1 in N-methyl pyrrolidone to produce the halo-l ,8-naphthylimide; and (b) reacting the halo-l ,8-naphthylimide with an amine A2 which may the same as amine Ar, in N-methyl pyrrolidone to produce the amino-1,8- naphthylimide. The second stage of this preparation, (b), is a second aspect of the invention.
In the most preferred embodiment of the invention, a 2- or4-halo-i,8-naphthalic anhydride, and particularly preferabiy a 4-bromo or 4-chloro-1 ,8naphthalic anhydride, is reacted with a primary amine, preferably a primary alkylamine, in N-methyl pyrrolidone, to give the 2-or 4-alkylamino-N-alkyl-1,8- naphthylimide, in which the alkyl groups are the same. The primary amine A1 may be an arylamine, yielding a 2-or 4-arylamino-N-aryl-i ,8-naphthylamide.
In a preferred embodiment of the second aspect of the invention, a 2- or 4-halo-i,8-naphthylimide is reacted with a primary or secondary amine, such as a primary or secondary alkylamine, or with a cyclic secondary amine which may contain one or more heteroatoms. The 2-or 4-halol ,8-naphthylimide may be prepared by reaction between a 2- or4-halo-1,8-naphthalic anhydride and a primary amine in a solvent, such as ethanol, which will allow recovery of the 2- or 4-halo-i ,8-naphthylimide in in useful quantities, without undue substitution of the halo at the 2- or 4-position.
In a further aspect of the invention, a method of preparing an alkoxyl-1,8-naphthylimide, such as a 2 or 4-alkoxyl-l ,8-naphthylimide, comprises reacting a halo-l ,8-naphthylimide, such as a 2 or 4-bromo or 2 or 4-chloro-i,8-naphthylimidewith an alkali metal alkoxide, such as a sodium alkoxide, in N-methyl pyrrolidone. The alkoxide may be, for example, a methoxide.
Methods according to the invention produce amino-1,8-naphthylimides, such as 2 or 4-alkylamino-N-alkyl 1,8-naphthylimides, which may be purified to high levels of purity by simple recrystallisation techniques.
A reaction scheme is set out below for the preparation of 4-alkylamino-N-alkyl-1,8-naphthylimides and 4-alkoxy-N-alkyl-1 ,8-naphthylimides from 4-halo-i ,8-naphthalic anhydrides. Both the case in which the amine A2 is a primary amine and that in which it is a secondary amine are shown.
wherein: R', R2, R3, R4 and R5 are alkyl groups; M is an alkali metal; and Xis halogen.
The invention also encompasses cases in which the groups R1, R2, R3, R4 and R5 are organic residues other than alkyl groups.
It is particularly preferred that R1 and R4 be the same and that both stages of the reaction are carried out in
N-methyl pyrrolidone
The invention will be further described by the following examples.
Example 7
Preparation of4-n-butylamino-N-n-butyl- 1,8-naphthylimide (R 7t4=n-Bu) 4-bmmo-i ,8-naphthalic anhydride was prepared by the general method disclosed by Rule and Thompson,
J.Chem.Soc. 1937, 1765, except that the pH was maintained at 7. The crude product was recrystallised from nitrobenzene and washed with ether to give pure 4-bromo-i,8-naphthalic anhydride, m.p. 230"C.
This 4-bromo-i,8-naphthalic anhydride (1.5g) was dissolved in N-methyl pyrrolidone (7.35gì by warming and to the stirred mixture n-butylamine (1.65g) was added. The reaction mixture was warmed to ii 00C, and further n-butylamine (1.659) was introduced and the mixture kept at 66"C for 24 hours.
After the 24 hours, the excess n-butylamine and the N-methyl pyrrolidone were removed by vacuum distillation. The residual organic material was dissolved in chloroform and washed with water to recover n-butylamine hydrobromide and then butylamine. The chloroform was removed by distillation, ethanol was added to the residual or organic material to give, by crystallisation, essentially pure 4-n-butylamino-N-n butyl-1 ,8-naphthylimide (1 .35g), which was found, by HPLC to be pure. Recovery of some of the ethanol from the filtrate produced another fraction (0.095gì. The total recovery of the product was 1.2309 (70.2%).The IR spectrum, the 1H NMR spectrum, the UV spectrum and the m.p., 126-127"C, were identical with those of a sample of pure 4-n-butylamino-N-butyl-l ,8-naphthylimide, The product gave a single band by TLC in light petroleum - diethylether (1:1), unlike commercial samples of 4-n-butylamino-N-n-butyl-1,8-naphthylimide, which all contained some impurities.
Monitoring I HPLC of the reactions of this example showed that the reaction appears to start with the opening of the anhydride ring, followed by its closure resulting in the formation of the N-n-butylimide and then the production of 4-n-butylamino-N-butyl-1,8-naphthylimide.
Example 2 A further sample of 4-n-butylamino-N-n-butyl-i ,8-naphthylimide was prepared in a similar way to that of Example 1 except that the starting material was 4-chloro-l ,8-naphthalic anhydride. The reaction gave the same product as that of Example 1, although the reaction proceeded slightly more slowly.
Example 3
Preparation of 4-morpholino-N-n-butyl- 1,8-naphthylimide (R 1-n-Bu, R3-R4=-CH2CH20CH2CH2-) 4-chloro-N-n-butyl-i ,8-naphthylimide was prepared by interaction of 4-chloro-i ,8-naphthalic anhydride with n-butylamine in athanolic solution. Under these conditions no displacement of the 4-chloro substituent took place. (The 4-chloro-N-n-butyl-1 ,8-naphthylimide was isolated when its formation was complete as judged by HPLC monotiroing with the solvent acetonitrile-water (1:1) by the reversed phase method.The product was crystallised from the reaction mixture as a yellow solid, m.p. 1501 5iC. (Analysis: - found: C,67.06%; H,4.92%; N,4.85%; Cl,i 2.42%; required: C,66.78%; H,4.87%; N,4.87%; Cl,12.34%.). The 1H NMR spectrum and the TLC chromatogram were as expected.The 4-chloro-N-n-butyl-i ,8-naphthylimide was
reacted with morpholine in N-methyl pyrrolidone solution giving, at 55"C after 24 hours, the product 4-morpholino-N-n-butyl-l ,8-na phthylimide, which was isolated in a similar manner to the products in
Examples 1 and 2, by removal of the excess morpholine and the solvent, followed by chloroform extraction, washing with water and evaporation of the chloroform solution. After crystallisation of the residual fluorescent yellow solid, 4-morpholino-N-n-butyl-i ,8-naphthylimide was obtained as a yellow microcrystalline material, m.p.138-140 C. (Analysis: -found: C,71.34%; H,66.6%; N,8.38%. Required: C,71.00%;
H,6.51%; N,8.28%.).
Example 4 Preparation of4-methoxy-N-n-butyl- l,8-naphthylimides (R 1=n-Bu, R5=CH3-) 4-chloro-N-butyl-1,8-naphthylimide was reacted with sodium methoxide in N-methyl pyrrolidone to give the product. The product was also obtained by a similar reaction starting with 4-bromo-N-n-butyl-l ,8- naphthylimide.
Example 5
Preparation of 4-n-propylamino-N-n-propyl- l,S-naphthylimide (R 7'4=n-propyl) 4-bromonaphthalic anhydride (1.5g) was dissolved by warming in N-methyl pyrrolidone (7.359) and to the stirred mixture n-propylamine (1 .3g) was added. A precipitate formed which slowly dissolved as the temperature was raised. The reaction mixture was maintained at 1 15"C for ten minutes and further n-propylamine (1.3g) was added, after which the temperature was allowed to fall and then maintained at 65"C for twenty four hours. After this, the excess n-propylamine and the solvent, N-methyl pyrrolidone, were removed and recovered successively by vacuum distillation.The residual material was dissolved in chloroform and the chloroform solution was washed with water. The chloroform was distilled off and the residual fluorescent material was crystallised from ethanol to give pure 4-n-propylamino-N-propyl 1,8naphthylimide, m.p. 167"-168"C, 45% yield, having the expected 1H NMR spectrum. Recovery of further material was possible through concentration of the filtrate both crops gave single bands by TLC examination in light petroleum diethyl ether (1:1).
Example 6
Preparation of 4-n-hexylamino-N-n-hexyl- 1,8-naphthylimide (R tt4=n-Hexyl) 4-bromonaphthalic anhydride (1.5g) in N-methyl pyrrolidone (7.359) was warmed until dissolved.
n-hexylamine (3ml) was added, and the mixture was heated at 1 35'C for ten minutes, during which time the precipitated material dissolved. Further n-hexylamine (2.72ml) was added, and the reaction mixture was left stirring for 24 hours at 66 C. The residual material upon recovery of the excess n-hexylamine and the solvent,
N-methyl pyrrolidone, was dissolved in chloroform and the solution washed with water. The chloroform was removed by distillation and the product crystallised from ethanol, whereby pure 4-n-hexylamino-N-n-hexyl1 ,8-naphthylimide, m.p.60 -62 C, 56% yield, was obtained having the expected spectroscopic properties (IR and 1H NNR spectra), and giving a single band by TLC in chloroform - light petroleum,40 -60 C (70:30). By evaporation of the filtrate a further crop of the product was obtained.
Example 7 Preparation of 4-n-octylamino-N-n-octyl- l,8-naphthylimide (R 1,4=n-octyl) 4-bromonaphthalic anhydride (1 .5g) in N-methyl pyrrolidone was treated with n-octylamine (3.6ml), and after the reaction mixture had been heated for ten minutes at 128 C, further n-octylamine (3.5ml) was introduced and the temperature maintained at 66"C for twenty four hours. The excess n-octylamine and the solvent, N-methyl pyrrolidone, were recovered by vacuum distillation (55 C/0.4mm Hg). The solid residue was dissolved in chloroform and the solution was washed with water.The chloroform solution was dried with magnesium sulphate and the filtrate concentrated to give an oil which was crystallised from ethanol to give pure 4-n-octylamino-N-n-octyl-i ,8-naphthylamide, m.p.83 -85 C, having the expected spectroscopic properties.
Example 8 Preparation of 4-alkylamino-N-pheny!- l,8-naphthylamide (R =alkyl, R4=phenyl) 4-bromo-N-phenyl-i,8-naphthylamide prepared from 4-bromonaphthalic anhydride and aniline in ethanol was reacted with a variety of n-alkylamines in N-methyl pyrrolidone to give 4-alkylamino-N-phenyl-i ,8- naphthylamide.
The preparative routes of the invention produce amino-l ,8-naphthylimides, and particularly 4-alkylamine N-alkyl-i ,8-naphthylimides, in yields and purities far better than those obtained with prior art methods of preparation. Of the preferred starting materials,4-chloro-1,8-naphthalic anhydride is a commercially available raw material, and 4-bromo-1,8-naphthalic anhydride is readily synthesised from commercially available naphthalic -1,8-anhydride.
The present invention thus provides an efficient and economically advantageous route for the preparation of amino-1,8-naphthylimides, and in particular of 4-alkylamino-N-alkyl-1,8-naphthylimides.
Claims (21)
1. A method of preparing a y-amino-1,8-naphthylimide, wherein y is 2 or 4, comprising:
(a) reacting a y-halo-1,8-naphthalic anhydride with a primary amine A1 in N-methyl pyrrolidone to produce the y-halo-l ,8naphthyiimide; and
(b) reacting they-halo-i ,8-naphthalimide with an amine A2, which may be the same as primary amine A1, in N-methyl pyrrolidone to produce they-amino-1 ,8-naphthylimide.
2. A method of preparing a y-amino-i,8-naphthylimide, wherein y is 2 or 4, comprising reacting a y-halo-i ,8-naphthylimide with an amine A2 in N-methyl pyrrolidone.
3. A method according to claim 1 in which the primary amine A1 is an alkylamine, whereby a y-halo-N-alkyl-1,8-naphthylimide, wherein y is 2 or 4, is produced by the reaction between the y-halo-1,8-the naphthalic anhydride and amine A.
4. A method according to claim 3 in which the primary amine A1 is n-butylamine and the product is a y-halo-N-butyl-1,8-naphthylimide, wherein y is 2 or 4.
5. A method according to claim 1,2,3 or 4 in which the amine A2 is a primary or secondary alkylamine, whereby a y-alkylamino-i ,8-naphthylimide, wherein y is 2 or 4, is produced by the reaction between the y-halo-l ,8-naphthylimide and amine A2.
6. A method according to claim 1, 2, 3 or 4, in which the amine A2 is a cyclic secondary amine, which may contain one or more hetero atoms.
7. A method according to claim 5 in which the amine A2 is n-butylamine, and the product is a y-n-butylamino-1 ,8-naphthylimide, wherein y is 2 or 4.
8. A method according to claim 6 in which the amine A2 is morpholine, and the product is a y-morpholino-1,8-naphthylimide, wherein y is 2 or 4.
9. A method of preparing a y-alkoxy-i ,8-naphthylimide, wherein y is 2 or 4, comprising reacting a y-halo-1,8-naphthylimide with a alkali metal alkoxide in N-methyl pyrrolidone.
10. A method according to claim 9 in which the alkali metal alkoxide is a methoxide, whereby the product is a y-methoxy-l ,8-naphthylimide, wherein y is 2 or4.
11. A method according to claim 9 or 10 in which the alkali metal is sodium.
12. A method according to any of claims 9 to 11 for producing a y-alkoxy-N-alkyl-1,8-naphthylimide, wherein y is 2 or 4, comprising reacting a y-halo-N-alkyl-i ,8-naphthylimide with an alkali metal alkoxide.
13. a method according to claim 12 in which the amine is n-butylamine.
14. A method of preparing a y-halo-i ,8-naphthylimide, wherein y is 2 or 4, comprising reacting a y-h;alo-l ,8-naphthalic anhydride with a primary amine A1 in ethanol.
15. A method according to any preceding claim wherein the halogen is bromine.
16. A method according to any of claims 1 to 14 wherein the halogen is chlorine.
17. A method according to any preceding claim in which y is 4.
18. A method substantially as described with reference to any of Examples 1,2 or 5 to 7.
19. A method substantially as described with reference to Example 3.
20. A method substantially as described with reference to Example 4.
21. A method substantially as described with reference to Example 8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8526587A GB2183667B (en) | 1985-10-29 | 1985-10-29 | Preparation of amino-1;8-naphthalimides. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8526587A GB2183667B (en) | 1985-10-29 | 1985-10-29 | Preparation of amino-1;8-naphthalimides. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8526587D0 GB8526587D0 (en) | 1985-12-04 |
| GB2183667A true GB2183667A (en) | 1987-06-10 |
| GB2183667B GB2183667B (en) | 1989-11-22 |
Family
ID=10587389
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8526587A Expired GB2183667B (en) | 1985-10-29 | 1985-10-29 | Preparation of amino-1;8-naphthalimides. |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2183667B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0398764A2 (en) * | 1989-05-19 | 1990-11-22 | Nec Corporation | An organic thin-film el device |
| WO1994011726A1 (en) * | 1992-11-16 | 1994-05-26 | Microbiomed Corporation | Non-azo 1,8-naphthalimide dyes for the detection and quantitation of a paramagnetic metal cation in a non-aqueous medium |
| EP0937752A2 (en) * | 1998-02-18 | 1999-08-25 | Milliken Research Corporation | Naphthalimide colorants with improved compatibility in refrigeration and air conditioning lubricants |
| WO2000031039A1 (en) * | 1998-11-25 | 2000-06-02 | Merck Patent Gmbh | Substituted benzo[de]isoquinoline-1,3-diones |
| WO2007062002A3 (en) * | 2005-11-21 | 2008-07-31 | Gen Electric | Fluorescent brighteners and compositions thereof, methods of preparation and uses |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1457478A (en) * | 1974-02-20 | 1976-12-01 | Hoechst Ag | 4-amino-1,8-naphthalic acid-imide-3-sulphonic acid and process for preparing them |
| GB1465443A (en) * | 1974-05-15 | 1977-02-23 | Hoechst Ag | Process for the preparation of 4-amino-1,8-naphthalic acid-n- arylimide compounds |
-
1985
- 1985-10-29 GB GB8526587A patent/GB2183667B/en not_active Expired
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1457478A (en) * | 1974-02-20 | 1976-12-01 | Hoechst Ag | 4-amino-1,8-naphthalic acid-imide-3-sulphonic acid and process for preparing them |
| GB1465443A (en) * | 1974-05-15 | 1977-02-23 | Hoechst Ag | Process for the preparation of 4-amino-1,8-naphthalic acid-n- arylimide compounds |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0398764A2 (en) * | 1989-05-19 | 1990-11-22 | Nec Corporation | An organic thin-film el device |
| EP0398764A3 (en) * | 1989-05-19 | 1991-10-09 | Nec Corporation | An organic thin-film el device |
| WO1994011726A1 (en) * | 1992-11-16 | 1994-05-26 | Microbiomed Corporation | Non-azo 1,8-naphthalimide dyes for the detection and quantitation of a paramagnetic metal cation in a non-aqueous medium |
| GB2287317A (en) * | 1992-11-16 | 1995-09-13 | Microbiomed Corp | Non-azo 1,8-naphthalimide dyes for the detection and quantitation of a paramagnetic metal cation in a non-aqueous medium |
| GB2287317B (en) * | 1992-11-16 | 1997-06-18 | Microbiomed Corp | Non-azo 1,8-naphthalimide dyes for the detection and quantitation of a paramagnetic metal cation in a non-aqueous medium |
| EP0937752A2 (en) * | 1998-02-18 | 1999-08-25 | Milliken Research Corporation | Naphthalimide colorants with improved compatibility in refrigeration and air conditioning lubricants |
| EP0937752A3 (en) * | 1998-02-18 | 1999-12-08 | Milliken Research Corporation | Naphthalimide colorants with improved compatibility in refrigeration and air conditioning lubricants |
| WO2000031039A1 (en) * | 1998-11-25 | 2000-06-02 | Merck Patent Gmbh | Substituted benzo[de]isoquinoline-1,3-diones |
| WO2007062002A3 (en) * | 2005-11-21 | 2008-07-31 | Gen Electric | Fluorescent brighteners and compositions thereof, methods of preparation and uses |
| US7608715B2 (en) | 2005-11-21 | 2009-10-27 | Sabic Innovative Plastics Ip B.V. | Fluorescent brighteners, methods of preparation thereof, fluorescent brightener compositions, and methods of preparation and uses thereof |
| US8183310B2 (en) | 2005-11-21 | 2012-05-22 | Sabic Innovative Plastics Ip B.V. | Fluorescent brighteners, methods of preparation thereof, fluorescent brightener compositions, and methods of preparation and uses thereof |
| US8507590B2 (en) | 2005-11-21 | 2013-08-13 | Sabic Innovative Plastics Ip B.V. | Fluorescent brighteners, methods of preparation thereof, fluorescent brightener compositions, and methods of preparation and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| GB2183667B (en) | 1989-11-22 |
| GB8526587D0 (en) | 1985-12-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19921029 |