GB859394A - Process for preparing substituted tetracyclines - Google Patents
Process for preparing substituted tetracyclinesInfo
- Publication number
- GB859394A GB859394A GB25420/58A GB2542058A GB859394A GB 859394 A GB859394 A GB 859394A GB 25420/58 A GB25420/58 A GB 25420/58A GB 2542058 A GB2542058 A GB 2542058A GB 859394 A GB859394 A GB 859394A
- Authority
- GB
- United Kingdom
- Prior art keywords
- tetracycline
- morpholinomethyl
- hydrogen
- acid
- methyl
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
- C07C237/26—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton of a ring being part of a condensed ring system formed by at least four rings, e.g. tetracycline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
- C07C2603/42—Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings
- C07C2603/44—Naphthacenes; Hydrogenated naphthacenes
- C07C2603/46—1,4,4a,5,5a,6,11,12a- Octahydronaphthacenes, e.g. tetracyclines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Substituted-N1- (primary or secondary aminomethyl) tetracyclines are prepared by reacting a compound of formula: <FORM:0859394/IV(b)/1> where TC represents all except the carboxamido group of tetracycline, oxytetracycline, chlortetracycline or bromtetracycline, and B is a primary or secondary amino group with at least one equivalent of a hydrogen replacing agent whereby an active hydrogen located on a carbon atom in a phenolic ring or on an oxygen atom is replaced. The hydrogen replacing agent is an acid halide, acid anhydride, alkyl haloformate, aralkyl haloformate, phosgene, an epoxide, beta propiolactone, dihydropyran, an olefine, a halogen, a phosphorous halide, halosulphuric acid, iodoacetic acid, a diazonium salt, an isocyanate, nitrous acid, nitric acid, sulphuryl chloride, a diazoalkane, a tertiary alcohol boron trifluoride complex, a sulphur tri-oxide dialkylamine complex, an alkyl orthoformate, phenyllithium and carbon dioxide in sequence, and mercuric acetate and sulphur dichloride. Radical B may be a secondary amino group consisting of di (lower) alkylamino, pyrrolidino, piperidino, morpholino, 2, 6-dimethyl-morpholino, N1-(lower) alkyl piperazino, pipecolino or dibenzylamino. Reactions take place at -40 to 50 DEG C. in anhydrous solvents such as pyridine, glacial acetic acid, ethyl carbamate, N, N-dimethyl acetamide, N-methyl-2- pyrrolidone, 1, 2-dimethoxyethane, N, N-di methyl formamide, diethylene glycol dimethyl ether, formamide and dimethyl sulphoxide. The substituted -N1- (primary or secondary aminomethyl) tetracycline is reduced to the corresponding substituted tetracycline by (a) catalytic reduction by hydrogen in a solvent such as methanol or (b) reduction by means of aqueous solution of a bisulphite especially sodium bisulphite. Examples describe the preparation of (a) 3-nitrophthalyl -N1- (morpholino-methyl) tetracycline from N1-morpholinomethyl) tetracycline and 3-nitrophthalic anhydride (b) monobenzoyl-N1-(dibenzylamino methyl) tetracycline from N1-(dibenzylaminomethyl) tetracycline and benzoyl chloride (c) p-nitrobenzoyl-N1-(morpholinomethyl) tetracycline using p-nitrobenzoyl chloride and N1-(morpholinomethyl) tetracycline (d) p-toluenesulphonyl-N- (morpholinomethyl) tetracycline using p-toluenesulphonyl-chloride and N1-(morpholinomethyl) tetracycline; (e) p-toluenesulphonyltetracycline by reducing (d) with hydrogen in presence of Raney Nickel catalyst; (f) monobenzoyl-N-1 (morpholinomethyl) tetracycline using benzoyl chloride and N1-(morpholinomethyl) tetracycline; (g) monobenzoyl tetracycline by reducing (b) with catalytic hydrogen or aqueous sodium bisulphite (h) o-carbethoxy-N1 (morpholinomethyl) tetracycline using N1 (morpholinomethyl) tetracycline and ethyl chloro formate; (i) o-carbethoxy-N1-(morpholinomethyl) tetracycline by reducing (j) with catalytic hydrogen or aqueous sodium bisulphite; (k) p-nitrobenzoyl tetracycline by reducing (c) with catalytic hydrogen (d) monobenzoyl -N1- (dibenzylaminomethyl) tetracycline using benzoyl chloride and N1-(dibenzylaminomethyl) tetracycline (m) p-nitrophenylazo-N1-morphilinomethyl tetracycline hydroacetate <FORM:0859394/IV(b)/2> from diazotised p-nitroaniline and N1-morpholinomethyl tetracycline followed by treatment with acetic acid (n) p-nitrophenylazo-N1-pyrrolidino methyl tetracycline dihydroacetate as in (m) using N1-(pyrrolidino methyl) tetracycline. Salts may be formed with hydrochloric, sulphuric, sulphonic, tartaric, hydrobromic, hydriodic, glycollic, citric, acetic and other fatty acids. The compounds may be used as a general disinfectant and veterinary medicine (see Group VI) or a preservative of fish. Specification 809,585 is referred to.ALSO:A veterinary preparation in the form of a capsule or suspension in a vegetable oil contains a substituted -N 1- (primary-or secondary-aminomethyl) tetracycline prepared by reacting a compound of formula: <FORM:0859394/VI/1> where TC represents all except the carboxamido group of tetracycline, oxytetracycline, chlortetracycline or bromtetracycline and B represents a primary or secondary amino group, with at least one equivalent of a hydrogen replacing reagent wherein an active hydrogen located on a carbon atom in a phenolic ring or on an oxygen atom is replaced (see Group IV (b)). The tetracycline may be in the form of the hydrochloride, sulphate, sulphamate, tartrate, hydrobromate, hydriodate, glycollate, citrate, maleate, phosphate, succinate or acetate. Aqueous solutions or suspensions may be used as general disinfectants. The compounds may be used for the preservation of fish at the rate of 0,1 to 1,000 mgm/kg of weight of the fish. They are used in solution or suspension in a liquid e.g. water or as a powder with a diluent such as talc. Specification 809,585 is referred to.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US859394XA | 1957-08-08 | 1957-08-08 |
Publications (1)
Publication Number | Publication Date |
---|---|
GB859394A true GB859394A (en) | 1961-01-25 |
Family
ID=22194977
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB25420/58A Expired GB859394A (en) | 1957-08-08 | 1958-08-07 | Process for preparing substituted tetracyclines |
Country Status (1)
Country | Link |
---|---|
GB (1) | GB859394A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3137627A (en) * | 1962-03-12 | 1964-06-16 | Bristol Myers Co | Nu-(1-pyrrolidinomethyl) tetracycline and acid compositions for aqueous acidified injections having a ph of not more than about 4 |
-
1958
- 1958-08-07 GB GB25420/58A patent/GB859394A/en not_active Expired
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3137627A (en) * | 1962-03-12 | 1964-06-16 | Bristol Myers Co | Nu-(1-pyrrolidinomethyl) tetracycline and acid compositions for aqueous acidified injections having a ph of not more than about 4 |
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