US3803235A - Novel acetophenone oxime derivatives - Google Patents

Novel acetophenone oxime derivatives Download PDF

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Publication number
US3803235A
US3803235A US00256113A US25611372A US3803235A US 3803235 A US3803235 A US 3803235A US 00256113 A US00256113 A US 00256113A US 25611372 A US25611372 A US 25611372A US 3803235 A US3803235 A US 3803235A
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formula
compounds
novel
solution
vacuum
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US00256113A
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English (en)
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Dijk J Van
J Zwagemakers
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US Philips Corp
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US Philips Corp
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)

Definitions

  • the new compounds may be prepared and formulated by known methods.
  • the invention relates to novel acetophenone oxime derivatives of the General Formula 1 (see formulae).
  • Hal indicates a chlorine or bromine atom
  • R is a hydrogen atom or a C-Ri group in which R denotes a hydrogen atom, an alkyl group or an alkoxy group containing from 1 to 11 carbon atoms or a group of the Formula 2, in which formula Hal denotes a chlorine or bromine atom.
  • the amount to be daily administered will be from 50 to 1000 mg. As a rule from to 500 mg. daily Will be suflicient.
  • the anti-inflammatory elfect of the compounds was determined in the carragheenin test which is carried out according to a modification of the method of Winter, Risley and Nuss, Proc. Soc. Exp. Biol., 111, 544 (1962).
  • the compounds to be tested were suspended in a 1 percent by weight solution of tragacanth in water and orally administered to male rats (weight about 220 g.) which were made to fast for the 16 hours preceding the test.
  • the administration of the substance was immediately followed by a water loading of 5 ml.
  • One hour afterwards 0.05 ml. of a 1.5 percent by weight carragheenin solution was intraplantarly injected and the thickness of the foot (dorsal-plantar distance) was determined with a micrometer.
  • BB value is computed, i.e. the dosage which gives a 50 percent reduction of the swelling.
  • the analgesic elfect was determined by a modification of the method of Randall and Sellito (Arch Int. Pharmacodyn., 109 409 (1957)).
  • the reduction of the pain response due to increasing pressure on a yeast-inflamed rat foot is used as the criterion for the analgesic activity.
  • the test is carried out on male rats having weights between 100 g. and 500 g. One hour before the administration of the test compound the animals are given an intraplanar injection of 0.1 ml. of a 20% yeast suspension. The compounds to be tested are suspended in a 1% tragacanth solution and administered orally. One, two and four hours after administration of the test substance the pain threshold value with increasing pressure on the inflamed foot is measured. As a control the pain reaction of a group of animals not treated with a pharmacon was determined.
  • the results obtained are expressed as a percentage of the mean control value. From the results of a series of dosages an ED value is calculated, i.e. the dosage which produced a 100% rise of the pain threshold.
  • the compounds according to the Formula 1 can be prepared by known methods.
  • the invention relates to a method of producing novel acetophenone oxime derivatives which is characterized in that compounds of the Formula 1, where Hal represents a chlorine or a bromine atom and R is a hydrogen atom or a group (J-R1 where R, is a hydrogen atom, an alkyl group or an alkoxy group containing from 1 to 11 carbon atoms or a group of the Formula 2, in which formula Hal denotes a c'hlorine or a bromine atom, are prepared by methods which are known for preparing compounds of this type and by analogous methods.
  • the compounds may be prepared by reacting a compound of the Formula 3 with a compound of the Formula 4, in which formulae the symbols have the aforementioned meanings.
  • This reaction is preferably carried out in an inert solvent such, for example, as dimethylformamide, dimethylsulfoxide, alcohols and the like, at temperatures between room temperature and the boiling point of the reaction mixture.
  • the compounds may also be obtained by reacting a compound of the Formula 5, in which M represents a hydrogen atom or a metal atom, with a compound of the Formula 6, in which formulae the symbols have the same meaning as in the Formula 1 and R represents a halogen atom or a tosyloxy group.
  • M represents a hydrogen atom
  • R represents a halogen atom or a tosyloxy group.
  • the compounds may furthermore be prepared by reacting a compound of the Formula 7, where R represents a halogen atom or a tosyloxy group, with a compound of the Formula 8, in which R has the same meaning as in the Formula 1.
  • This reaction is preferably carried out in the presence of a base. Lower alcohols may be used as solvents.
  • the reaction is usually carried out at a temperature between C. and 150 C.
  • the esters of the Formula 1 may alternatively be obtained by reacting an alcohol of the Formula 1 with a compound of the Formula 9, in which R, represents an OH-group, a halogen atom, an alkoxy group containing from 1 to 4 carbon atoms or the group and R has the same meaning as in the Formula 1, with the understanding that when R represents a hydrogen atom R is a halogen atom, an alkoxy group or an OH- group.
  • the reaction with compounds of the Formula 9, in which R represents a halogen atom or an alkoxy group is preferably carried out under alkaline conditions, the other reactions under acid conditions.
  • the reaction temperature as a rule lies between 0 C. and 150 C. Benzene, pyridine, dimethylformamide and the like may be used as solvents.
  • the reaction is preferably carried out under basic conditions at temperatures between 20 C. and 80 C. Lower alcohols may be used as the solvents.
  • the compounds according to the invention may be worked up into pharmaceutical preparation such, for example, as tablets, pills, powders, injection liquids, ointments, suppositories, drages and the like by known methods.
  • pharmaceutical preparation such as tablets, pills, powders, injection liquids, ointments, suppositories, drages and the like.
  • the invention also relates to the production of pharmaceutical preparations and to the preparations themselves.
  • Suitable carrier material are the substances generally used for this purpose in pharmacy.
  • the solvent was distilled off in a vacuum at 40 C. and the residue was suspended in 35 ml. of N,N-dimethylformamide. This solution was mixed with 6.7 g. of 2-bromoethanol, after which the mixture was stirred at room temperature for 24 hours. Then the solvent was largely distilled ofif in a vacuum, the residue was mixed with 100 ml. of water and the mixture was extracted twice with 25 ml. portions of chloroform. The extract was dried over anhydrous sodiumsulfate. The chloroform was distilled off and subsequently the residue was subjected to fractional distillation in a vacuum. The fraction having a boiling range from 154 C. to 162 C. and 0.7 mm.
  • the aqueous layer was washed once with 500 ml. of diethylether and then the collected ethereal extracts were washed twice with portions of 300 ml. water and then dried over anhydrous sodium sulfate. After removal of the ether by distillation the residue was subjected to fractional distillation in a vacuum. The fraction having a boiling range from 154 C. to 162 C. at 0.77 mm. of mercury was chromatographically purified on a silica gel column with a benzene-ethylacetate mixture (3:1) as the eluant. The substance obtained was crystallized from petroleum ether containing 4% of benzene and melted at 41-42 C.
  • Tablet.-200 g. of 0-(Z-hydroxyethyl)-4'-bromoacetophenone oxime was mixed with 190 g. of sec. calciumphosphate, 90 g. of microcrystalline cellulose and 120 g. of mixture comprising 200 parts of maize starch, 32 parts of talcum and 4 parts of magnesium stearate until a homoin which Hal represents a chlorine or a bromine atom.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US00256113A 1971-05-28 1972-05-23 Novel acetophenone oxime derivatives Expired - Lifetime US3803235A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
NL7107360A NL7107360A (enrdf_load_stackoverflow) 1971-05-28 1971-05-28

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US3803235A true US3803235A (en) 1974-04-09

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US (1) US3803235A (enrdf_load_stackoverflow)
BE (1) BE784076A (enrdf_load_stackoverflow)
CH (3) CH587234A5 (enrdf_load_stackoverflow)
DE (1) DE2225190C3 (enrdf_load_stackoverflow)
ES (1) ES403209A1 (enrdf_load_stackoverflow)
FR (1) FR2140047B1 (enrdf_load_stackoverflow)
GB (1) GB1347433A (enrdf_load_stackoverflow)
NL (1) NL7107360A (enrdf_load_stackoverflow)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4242348A (en) * 1970-06-11 1980-12-30 Duphar International Research B.V. Novel basic substituted-alkylidenamino-oxylalkyl-carboxylic-acid esters
US4388106A (en) * 1978-08-31 1983-06-14 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4488899A (en) * 1978-08-31 1984-12-18 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4488898A (en) * 1978-08-31 1984-12-18 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4488900A (en) * 1978-08-31 1984-12-18 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4548756A (en) * 1977-03-02 1985-10-22 Ciba Geigy Corporation Oxime ethers
US4581060A (en) * 1977-03-02 1986-04-08 Ciba-Geigy Corporation Compositions, which promote plant growth and protect plants, based on oxime ethers and oxime esters
EP1925610A1 (de) * 2006-11-24 2008-05-28 Bayer CropScience AG Verfahren zur Herstellung von 2-Aminooxyethanol

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH632130A5 (en) * 1977-03-02 1982-09-30 Ciba Geigy Ag Compositions on the basis of oxime ethers, oxime esters or oxime carbamates which are suitable in agriculture for crop protection

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3040097A (en) * 1959-04-06 1962-06-19 Purdue Research Foundation Beta-hydroxy alkyl ethers of oximes and production thereof

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4242348A (en) * 1970-06-11 1980-12-30 Duphar International Research B.V. Novel basic substituted-alkylidenamino-oxylalkyl-carboxylic-acid esters
US4317835A (en) * 1970-06-11 1982-03-02 Duphar International Research B.V. Novel basic substituted-alkylidenamino-oxyalkyl-carboxylic acid esters
US4581060A (en) * 1977-03-02 1986-04-08 Ciba-Geigy Corporation Compositions, which promote plant growth and protect plants, based on oxime ethers and oxime esters
US4548756A (en) * 1977-03-02 1985-10-22 Ciba Geigy Corporation Oxime ethers
US4439230A (en) * 1978-08-31 1984-03-27 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4505742A (en) * 1978-08-31 1985-03-19 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4450000A (en) * 1978-08-31 1984-05-22 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4486224A (en) * 1978-08-31 1984-12-04 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4488899A (en) * 1978-08-31 1984-12-18 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4488898A (en) * 1978-08-31 1984-12-18 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4488900A (en) * 1978-08-31 1984-12-18 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4439228A (en) * 1978-08-31 1984-03-27 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4437879A (en) 1978-08-31 1984-03-20 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
US4388106A (en) * 1978-08-31 1983-06-14 Ciba-Geigy Corporation Oxime derivatives for protecting plant crops
EP1925610A1 (de) * 2006-11-24 2008-05-28 Bayer CropScience AG Verfahren zur Herstellung von 2-Aminooxyethanol
WO2008061616A1 (de) * 2006-11-24 2008-05-29 Bayer Cropscience Ag Verfahren zur herstellung von 2-aminooxyethanol
US20100048953A1 (en) * 2006-11-24 2010-02-25 Bayer Cropscience Ag Process for Preparing 2-Aminooxyethanol
US7968747B2 (en) 2006-11-24 2011-06-28 Bayer Cropscience Ag Process for preparing 2-aminooxyethanol

Also Published As

Publication number Publication date
FR2140047B1 (enrdf_load_stackoverflow) 1975-06-20
DE2225190A1 (de) 1973-01-11
ES403209A1 (es) 1976-01-16
CH590829A5 (enrdf_load_stackoverflow) 1977-08-31
DE2225190B2 (de) 1980-10-16
BE784076A (fr) 1972-11-27
GB1347433A (en) 1974-02-27
CH590828A5 (enrdf_load_stackoverflow) 1977-08-31
CH587234A5 (enrdf_load_stackoverflow) 1977-04-29
FR2140047A1 (enrdf_load_stackoverflow) 1973-01-12
DE2225190C3 (de) 1982-01-21
NL7107360A (enrdf_load_stackoverflow) 1972-11-30

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