GB601768A - Process for the manufacture of derivatives of acridine - Google Patents
Process for the manufacture of derivatives of acridineInfo
- Publication number
- GB601768A GB601768A GB2657645A GB2657645A GB601768A GB 601768 A GB601768 A GB 601768A GB 2657645 A GB2657645 A GB 2657645A GB 2657645 A GB2657645 A GB 2657645A GB 601768 A GB601768 A GB 601768A
- Authority
- GB
- United Kingdom
- Prior art keywords
- methoxy
- phenol
- chloro
- acridine
- aminopyrimidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 125000000641 acridinyl group Chemical class C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000000034 method Methods 0.000 title 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract 12
- 150000001251 acridines Chemical class 0.000 abstract 8
- 238000010438 heat treatment Methods 0.000 abstract 8
- 239000011541 reaction mixture Substances 0.000 abstract 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract 4
- 239000003513 alkali Substances 0.000 abstract 4
- 239000012458 free base Substances 0.000 abstract 4
- -1 hydroxy, nitro, amino Chemical group 0.000 abstract 4
- 239000000047 product Substances 0.000 abstract 4
- FVLAYJRLBLHIPV-UHFFFAOYSA-N pyrimidin-5-amine Chemical compound NC1=CN=CN=C1 FVLAYJRLBLHIPV-UHFFFAOYSA-N 0.000 abstract 4
- 235000011121 sodium hydroxide Nutrition 0.000 abstract 4
- 125000001424 substituent group Chemical group 0.000 abstract 4
- 125000003545 alkoxy group Chemical group 0.000 abstract 3
- CKWITQOQGJPKOE-UHFFFAOYSA-N 6-chloro-2-methoxy-9-phenoxyacridine Chemical compound C12=CC(OC)=CC=C2N=C2C=C(Cl)C=CC2=C1OC1=CC=CC=C1 CKWITQOQGJPKOE-UHFFFAOYSA-N 0.000 abstract 2
- DXGRQSKRHQCNMS-UHFFFAOYSA-N COC1=CC=C2N=C3C=CC(=CC3=C(C2=C1)Cl)C#N Chemical compound COC1=CC=C2N=C3C=CC(=CC3=C(C2=C1)Cl)C#N DXGRQSKRHQCNMS-UHFFFAOYSA-N 0.000 abstract 2
- 125000000217 alkyl group Chemical group 0.000 abstract 2
- 125000003277 amino group Chemical group 0.000 abstract 2
- 230000001203 anti-plasmodial Effects 0.000 abstract 2
- 229940027998 antiseptics and disinfectants Acridine derivatives Drugs 0.000 abstract 2
- 125000004104 aryloxy group Chemical group 0.000 abstract 2
- 150000001896 cresols Chemical class 0.000 abstract 2
- 125000001188 haloalkyl group Chemical group 0.000 abstract 2
- 229910052736 halogen Inorganic materials 0.000 abstract 2
- 125000005843 halogen group Chemical group 0.000 abstract 2
- 150000002367 halogens Chemical class 0.000 abstract 2
- 238000002955 isolation Methods 0.000 abstract 2
- 150000002576 ketones Chemical class 0.000 abstract 2
- 239000007788 liquid Substances 0.000 abstract 2
- 239000000203 mixture Substances 0.000 abstract 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 2
- 150000002989 phenols Chemical class 0.000 abstract 2
- 239000002244 precipitate Substances 0.000 abstract 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 2
- 150000003230 pyrimidines Chemical class 0.000 abstract 2
- 239000007858 starting material Substances 0.000 abstract 2
- 238000001665 trituration Methods 0.000 abstract 2
- SJZRECIVHVDYJC-UHFFFAOYSA-M 4-hydroxybutyrate Chemical group OCCCC([O-])=O SJZRECIVHVDYJC-UHFFFAOYSA-M 0.000 abstract 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Acridine derivatives having antiplasmodial properties and of the formula <FORM:0601768/IV(b)/1> wherein either or both Bz rings of the acridine nucleus may contain one or more substituents, e.g. alkyl, alkoxy, nitro, disubstituted amino or halogen, and wherein the pyrimidine nucleus may also contain one or more additional substituents, e.g. halogen atoms or alkyl, arylalkoxy, aryloxy, hydroxy, nitro, amino or substituted amino groups, are manufactured by heating a 5-aminopyrimidine with a mesohalogenated acridine in the presence of a phenol, or with a meso-phenoxyacridine (preferably also in the presence of a phenol, or without isolation from the reaction mixture obtained by heating a meso-halogenated acridine with a phenol). The phenol (e.g. phenol itself, a cresol or a higher alkylated phenol, or a mixture of alkylphenols) is preferably present in excess, and the resulting solution may be poured into a normally liquid ether or ketone (e.g. diethyl ether or acetone) to isolate the product in the form of its hydrohalide (from which the free base may be obtained, e.g. by trituration with aqueous alkali), or the free base may be directly isolated by pouring the reaction mixture into aqueous alkali. In examples: (1) 2-methoxy-6 : 9-dichloroacridine is heated with 2 : 5-diaminopyrimidine in phenol, the reaction mixture is poured into ether and the resulting precipitate is ground with cold dilute caustic soda to liberate 51-(2-methoxy-6-chloroacridyl-9) -amino-21-aminopyrimidine; (2) the same product is prepared by heating 2-methoxy-6-chloro-9-phenoxyacridine (obtained by heating 2-methoxy-6 : 9-dichloroacridine with phenol) with 2 : 5-diaminopyrimidine in phenol and pouring the reaction mixture into excess of cold dilute caustic soda; (3) the 2 : 5 - diamino-pyrimidine in (1) is replaced by 5-amino-pyrimidine, producing 51-(2-methoxy-6-chloroacridyl-9)-aminopyrimidine. Additional starting materials specified are, on the one hand, 9-chloro-, 9-bromo-, 2-methoxy-9-chloro-, 2-and 3-cyano-9-chloro-, 2-methoxy-6-cyano-9-chloro-, 2-methoxy-6 : 9-dibromo-, 2-dimethyl-amino-6 : 9-dichloro- and 2-methoxy - 7 - cyano-9-chloro-acridine; and, on the other hand, 2 : 4-dihydroxy-, 2 : 4 : 6-trihydroxy-, 2 : 4-dihydroxy - 6 - methyl-, 2 : 4 - dihydroxy - 6 - phenyl-, 2 : 6 - dimethyl - 4 - hydroxy - and 2 : 6 - dimethyl - 4 - chloro - 5 - aminopyrimidine, and 4 - hydroxy - 6 - methyl-, 4 : 6-dimethyl- and 4 : 6-dichloro-2 : 5-diaminopyrimidine.ALSO:Acridine derivatives having antiplasmodial properties and of the formula <FORM:0601768/IV (c)/1> wherein either or both Bz rings of the acridine nucleus may contain one or more substituents, e.g. alkyl, alkoxy, nitro, disubstituted amino or halogen, and wherein the pyrimidine nucleus may also contain one or more additional substituents, e.g. halogen atoms or alkyl, aryl, alkoxy, aryloxy, hydroxy, nitro, amino or substituted amino groups, are manufactured by heating a 5-aminopyrimidine with a meso-halogenated acridine in the presence of a phenol, or with a meso-phenoxy acridine (preferably also in the presence of a phenol or without isolation from the reaction mixture obtained by heating a meso-halogenated acridine with a phenol). The phenol (e.g. phenol itself, a cresol or a higher alkylated phenol, or a mixture of alkylphenols) is preferably present in excess, and the resulting solution may be poured into a p normally liquid ether or ketone (e.g. diethyl ether or acetone) to isolate the product in the form of its hydrohalide (from which the free base may be obtained, e.g. by trituration with aqueous alkali), or the free base may be directly isolated by pouring the reaction mixture into aqueous alkali. In examples: (1) 2-methoxy-6 : 9-dichloroacridine is heated with 2 : 5-diaminopyrimidine in phenol, the reaction mixture is poured into ether and the resulting precipitate is ground with cold dilute caustic soda to liberate 51-(2-methoxy-6-chloroacridyl-9) -amino-21-aminopyrimidine; (2) the same product is prepared by heating 2-methoxy-6-chloro-9-phenoxyacridine (obtained by heating 2-methoxy-6 : 9-dichloroacridine with phenol) with 2 : 5-diaminopyrimidine in phenol and pouring the reaction mixture into excess of cold dilute caustic soda; (3) the 2 : 5-diaminopyrimidine in (1) is replaced by 5-aminopyrimidine, producing 51-(2-methoxy-6-chloroacridyl-9)-aminopyrimidine. Additional starting materials specified are, on the one hand, 9-chloro-, 9-bromo-, 2-methoxy-9-chloro-, 2- and 3-cyano-9-chloro-, 2-methoxy-6-cyano-9-chloro-, 2-methoxy-6 : 9-dibromo-, 2-dimethylamino-6 : 9 - dichloro- and 2 - methoxy - 7 - cyano - 9 - chloro-acridine, and, on the other hand, 2 : 4-dihydroxy-, 2 : 4 : 6 - trihydroxy-, 2 : 4 - dihydroxy-6-methyl-, 2 : 4-dihydroxy-6-phenyl-, 2 : 6-dimethyl-4-hydroxy- and 2 : 6-dimethyl-4-chloro-5-aminopyrimidine, and 4-hydroxy-6-methyl-, 4 : 6-dimethyl- and 4 : 6-dichloro-2 : 5-diaminopyrimidine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US701414A US2465868A (en) | 1945-10-11 | 1946-10-05 | Process for the manufacture of derivatives of acridine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB601768A true GB601768A (en) | 1948-05-12 |
Family
ID=1740125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB2657645A Expired GB601768A (en) | 1945-10-11 | 1945-10-11 | Process for the manufacture of derivatives of acridine |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB601768A (en) |
-
1945
- 1945-10-11 GB GB2657645A patent/GB601768A/en not_active Expired
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