[go: up one dir, main page]

WO1982002046A1 - Procede de preparation de n-heterocycles-(alpha)2 - Google Patents

Procede de preparation de n-heterocycles-(alpha)2 Download PDF

Info

Publication number
WO1982002046A1
WO1982002046A1 PCT/DE1981/000225 DE8100225W WO8202046A1 WO 1982002046 A1 WO1982002046 A1 WO 1982002046A1 DE 8100225 W DE8100225 W DE 8100225W WO 8202046 A1 WO8202046 A1 WO 8202046A1
Authority
WO
WIPO (PCT)
Prior art keywords
residue
hydroxy
mol
carbon atoms
amino
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.)
Ceased
Application number
PCT/DE1981/000225
Other languages
German (de)
English (en)
Inventor
Ag Schering
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Schering AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Schering AG filed Critical Schering AG
Publication of WO1982002046A1 publication Critical patent/WO1982002046A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/06—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D263/12—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with radicals containing only hydrogen and carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D263/14—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/28—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/06—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings
    • C07D265/08—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D267/02—Seven-membered rings
    • C07D267/06—Seven-membered rings having the hetero atoms in positions 1 and 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D277/10—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/18—Nitrogen atoms

Definitions

  • the invention relates to a new process for the preparation of ⁇ 2 -N heterocycles.
  • the process products are suitable as intermediates for the production of active pharmaceutical ingredients, but also have biological activity themselves, such as, for example, as diuretics.
  • the process serves in particular to introduce ⁇ 2 -Gxazolin-, ⁇ 2 -Thiazolin and ⁇ 2 -Imidazolin protective groups in carboxylic acids.
  • ⁇ 2 -N-heterocycles such as, for example, ⁇ 2 -oxazolines, ⁇ 2 -thiazolines or ⁇ 2 -imidazolines
  • carboxylic acids or their derivatives and corresponding amines such as ethanolamine, cysteamine and 1,2-ethylenediamine by heating the components to 70-250 ° C
  • amines such as ethanolamine, cysteamine and 1,2-ethylenediamine
  • ⁇ 2 -thiazolines, ⁇ 2 -imidazolines or their higher-linked analogues are therefore very difficult or often not possible. It has now been found that the ⁇ 2 -N-heterocycles mentioned can be prepared under particularly mild conditions and directly from carboxylic acids or a carboxylic acid derivative by reaction with a suitable amine in a technically useful manner if the reaction with organic phosphines or organic phosphonium salts and perhalogenated hydrocarbons or ketones or with azodicarboxylic acid ediest ern in the presence of tertiary amines.
  • imirie or thioamides II e.g. N-ß-hydroxyethyl-phenylacetic acid amiü
  • phosphines and perhalogenated hydrocarbons can also be used with phosphines and perhalogenated hydrocarbons or with
  • the present process also offers the advantage of achieving high yields of ⁇ 2 -N-etching even without isolating the intermediates.
  • the invention thus relates to a process for the preparation of ⁇ 2 -N-heterocycles of the general formula I.
  • R 2 is hydrogen, optionally substituted by a hydroxy or amino group, alkyl having 1-6 C atoms, C 1 -C 4 alkoxycarbonyl, cyano or di-C 1 -C 4 alkylaminocarbonyl,
  • R 3 , R 4 , R 5 , R 6 , R 7 are hydrogen, alkyl which is optionally substituted by a hydroxyl or amino group and has 1-6 C atoms or aryl,
  • R 3 and R 4 together trimethylene, tetramethylene or 1, 3-butadienylene if R 2 and R 5 together represent a direct bond.
  • R 8 is hydroxy, C 1- C 6 alkoxy, C 1 -C 6 alkylthio, aryloxy or -thiorest, a Aralkyioxy- or -thiorest with 7-10 C atoms, a C 1 -C 4 - Represent trialkylsilyloxy or thio radical or a tri-C 7 -C 10 aralkylsilylexy or thio radical, and amines of the general formula III
  • R 2 , R 3 , R 4 , R 5 , Y and Z have the meaning given above, characterized in that with the aid of organic phosphines or phosphonium salts and perhalogenated carbon. Hydrogens or ketones or with the aid of azodicarboxylic acid diesters in the presence of tertiary amines.
  • R 1 in the meaning of an alkyl group with 1-19 C atoms are straight-chain and branched saturated hydrocarbon radicals with 1-19 C atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert.
  • R 5 , R 6 , R 7 and R 8 represent an alkyl radical with 1-6 C atoms, this is to be understood as radicals as already mentioned for R 1 .
  • Preferred alkyl radicals for R 2 to R 7 and R 8 are those with 1-4 C atoms. These alkyl radicals can also be substituted, preferably by hydroxy or amino.
  • alkyl radicals with 1-4 C atoms come into consideration, as have already been mentioned for R 1 .
  • Aralkyl radicals R 1 , R 2 , R 3 , R 3 , R 5 , R 6 , R 7 and R 8 are to be understood as straight-chain and branched radicals with 7-14 C atoms, such as, for example, benzyl, 1-phenylethyl, 2- Phenylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, 4-phenylbutyl, ⁇ -naphthylaethyl, ß-Na-phthylmethyl, 1- ( ⁇ -naphthyl) ethyl, 2- (ß-naphthyl) ethyl, 4- (ß-Naphthyl) -butyl, etc.
  • radicals with phenyl in the meaning of Ar with 7-10 C atoms which may be replaced by hydroxy, amino, nitro, fluorine, chlorine, bromine, C 1 -C 4 alkoxycarbonyl, Di -C 1 -C 4 -alkylaminocarbonyl, C 1 -C 4 -alkylaminocarbonyl, tri-C 1 -C 4 -alkylsilyloxy-, tetrahydropyranyloxy or benzoyloxy, preferably can be substituted by hydroxy, amino or chlorine.
  • Phenyl, ⁇ - and ⁇ -naphthyl, preferably phenyl, are suitable for the radicals R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 as aryl.
  • R 2 in the meaning of alkoxycarbonyl.
  • alkyl radicals for alk come into consideration: methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert. -Butyl and benzyl.
  • Dialkylaminocarbonyl in the meaning of R 2 should be a radical in which alkyl is a straight-chain saturated alkyl radical with 1-4 C atoms (methyl, ethyl, propyl, butyl).
  • n can have the size 0 to 3.
  • R 1 represents a cycloalkyl radical with 5-7 C atoms
  • Suitable 5- or 6-membered heterocycles with 1-3 N, O or S heteroatoms are: pyrryl, thienyl, pyridyl, imidazolyl, pyrazolyl, triazolyl, cxazolyl, thiazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, pyrazinyl, pyridazinyl , Azepinyl etc.
  • arylene means the residues o-, m- or p-phenylene and all possibilities which exist for the naphthylene residue.
  • Preferred residues are the phenylene residues.
  • R 1 can be straight-chain or branched-chain alkylene radicals such as, for example, methylene, ethylene, trimethylene, tetramethylene , Pentamethylene, hexamethylene, methyltrimethylene, ethylethylene, ethyltetraaethylene, etc., where m is 1 to 6.
  • the residues with m 1-4 should preferably be.
  • radicals C 1- C 6 alkoxy, C 1- C 6 alkylthio, aryloxy, arylthio, aralkylthio, aralkyioxy, C 1- C 4 -trialkylsilyloxy- or -thio or triaralkylsilyloxy- or -thio each correspond to those already for R 1 mentioned residues alkyl, aryl, aralkyl.
  • the starting materials II especially organic carboxylic acids such as acetic acid, adipic acid, fumaric acid, benzoic acid, terephthalic acid, trimesic acid, citric acid, phenylacetic acid, 2-phenyl propionic acid (hydratropic acid), pyruvic acid, mesoxalic acid, nicotinic acid, isonicotinic acid, naphthoic acid, cyclohexanecarboxylic acid, furancarboxylic acid, thiophenecarboxylic acid and come the already defined esters of these acids.
  • organic carboxylic acids such as acetic acid, adipic acid, fumaric acid, benzoic acid, terephthalic acid, trimesic acid, citric acid, phenylacetic acid, 2-phenyl propionic acid (hydratropic acid), pyruvic acid, mesoxalic acid, nicotinic acid, isonicotinic acid, naphthoic acid
  • Preferred amines III for the cyclization to ⁇ 2 -N-heterocycles in the 5-ring series are ethanolamine, 2-aminopropanol, 2-methyl-2-aminopropanol, tris (hydroxymethyl) methylamine, o-aminophenol,
  • Cysteamine 1,2-ethylenediamine, o-phenylenediamine, 1-amino-2-methylaminoethane, 1-amino-2-phenylamino- or 2-benzylaminoethane, and in the 6-ring series 3-aminopropanol, 2,3, 3-trimethyl-3-amino-1-propanol, 3-aminopropanethiol, 1,3-diaminopropane or 1,3-diamino ⁇
  • n determines the ring size of the
  • Suitable organic phosphines or phosphonium salts are R 9
  • Aryl phenyl, ⁇ - or ⁇ -naphthyl, preferably phenyl
  • aralkyl phenyl, ⁇ - or ⁇ -naphthyl, preferably phenyl
  • alkyl (with 7-10 carbon atoms as stated above), alkyl (with 1-6 carbon atoms as stated above), alkyl (with 1-6 carbon atoms as stated above), alkyl (with 1-6 carbon atoms as stated above), alkyl (with 1-6 carbon atoms as stated above), alkyl (with 1-6 carbon atoms as stated above), alkyl (with 1-6 carbon atoms as stated above), alkyl (with 1-6
  • Phenyl 0-alkyl (with 1-6 C atoms, see radical e for R.) and DiC 1- C 4 alkyl) -amino (preferably dimethylamino) or as
  • triarylphosphines are bound to a polymeric res
  • preferred reagents in which triarylphosphines are bound to a polymeric res.
  • Perhalogenated aliphatics and aralkyls and carbonyl compounds such as CCl 4 , CBrCl 3 , CBr 2 Cl 2 , CClBr 3 , CBr 4 , C 2 Cl 6 , C 6 H 5 -CCl 3 , CCl 3 -CO-CCl 3 CCl are used as electrophilic components 3 is -CH 3, CHBr 3, CCl 3 CN, CCl 3, etc. but preferably -CHO CCl 4 and C 2 C 16,
  • tert.Aeine in triethylamine, tri-n-propy ⁇ amine, tributylamine, diisopropylethylamine, dicyclohexylethylamine, benzyldimethylaain, pyridine, lutidine, collidine, 2-dimethylaminopyridine, 4-diaethylaminopyridine, quinoline, 1,4-diazobicyclo [4,3,0] non-5-ene (DBN), 1.8 -Diazobicyclo [5,4,0] undec-7-ene (DBU) 1,4-diazabicyclo [2.2.2] octane (DABCO), preferably triethylamine and pyridine.
  • the reaction is carried out in non-protic absolute solvents or solvent mixtures such as CCl 4 , chloroform, methylene chloride, benzene, toluene, ethyl ether, tetrahydrofuran, ethyl acetate, acetonitrile, dimethylformamide (DMF) or sulfolane, preferably in acetonitrile, pyridine or DMF.
  • non-protic absolute solvents or solvent mixtures such as CCl 4 , chloroform, methylene chloride, benzene, toluene, ethyl ether, tetrahydrofuran, ethyl acetate, acetonitrile, dimethylformamide (DMF) or sulfolane, preferably in acetonitrile, pyridine or DMF.
  • the reaction proceeds at temperatures between -20 ° C and 100 ° C, preferably at + 10 ° C to + 30 ° C. It is advantageous to use equivalent amounts of the amine component ( ⁇ -hydroxy- and ⁇ -mercaptoamine and
  • tert. Phosphine preferably triphenylphosphine
  • electrophile preferably CCl 4 or C 2 Cl 6
  • Amine preferably triethylamine
  • 2-3 equivalents preferably at least 4 equivalents.
  • An excess of the triethylamine causes a better solubility of the amine salts of the carboxylic acids.
  • These compounds can be used on very deactivated adsorbents such as e.g. Chromatograph aluminum oxide (A IV-V) or silica gel to which 30-40% water has been added, if possible using pressure, without large amounts of these substances being decomposed during the chromatography.
  • very deactivated adsorbents such as e.g. Chromatograph aluminum oxide (A IV-V) or silica gel to which 30-40% water has been added, if possible using pressure, without large amounts of these substances being decomposed during the chromatography.
  • MJ Miller et al. describe in JACS 198O, 7026 the cyclization of ⁇ -hydroxyhydroxamates with triphenylphosphine / diethyl azodicarboxylate. As a by-product, they receive oxazolines in 10-20% yield. It was therefore very surprising that the amides II (z.3. N- ⁇ -hydroxyethyl-phenylacetic acid amide) form 60-70% oxazolines under these cyclization conditions. It was also not foreseeable that the single-stage process starting from the carboxylic acid derivatives or carboxylic acids II and de amines III would yield far better yields of ⁇ 2 -N-heterocycles than the multi-stage process by MJ Miller.
  • 2-Anilino- ⁇ 2 -thiazoline The substance was prepared completely analogously to Example 12 starting from N-2-mercaptoethyl-N'-phenylurea. 2-Anilino- ⁇ 2 -thiazoline was recrystallized from dilute ethanol.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Polyoxymethylene Polymers And Polymers With Carbon-To-Carbon Bonds (AREA)
  • Epoxy Resins (AREA)
  • Paints Or Removers (AREA)
  • Adhesives Or Adhesive Processes (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
  • Graft Or Block Polymers (AREA)

Abstract

Procede de preparation de N-heterocycles-(Alpha)2 de formule generale I, (FORMULE) dans laquelle v signifie un nombre de 1 a 4, R1 signifie (si v = 1) l'hydrogene, l'un des restes suivants: alkyle avec 1 a 19 atomes de C, aralkyle avec 7 a 10 atomes de C ou cyclo-alkyle avec 5 a 7 atomes de C; ces restes etant eventuellement substitues par un hydroxy, amino, nitro, fluor, chlore, brome, C1-C4-alkoxycarbonyle, di-C1-C4-alkylaminocarbonyle, C1-C4-alkylaminocarbonyle, tri-C1-C4-alkylsilyloxy-, tetrahydropyranyloxy ou benzoyloxy; ou l'un des restes oxo-alkyle avec 1 a 6 atomes de C, aryle ou un heterocycle a 5 ou 6 chainons avec 1 a 3 atomes N, O ou S en tant qu'heteroatomes; R1 signifie (si v = 2) un reste arylene, un reste alkylene-(CH2)-m, dans lequel m signifie 1 a 6, et qui peut etre substitue par un hydroxy, oxo, amino, nitro, fluor, chlore, brome, tri-C1-C4-alkylsilyloxy, ou benzoyloxy; ou le reste -CH = CH-; R1 signifie (si v = 3 ou 4) un reste benzene a 3 ou 4 valences libres ou un reste alkylene-(CH2)-m a 3 ou 4 valences libres, dans lequel m est 1 a 6 et qui peut etre eventuellement substitue par un hydroxy, oxo, amino, nitro, fluor, chlore, brome, tri-C1-C4-alkylsilyloxy, tetrahydropyranyloxy, ou benzoyloxy; D signifie un reste imino ou une liaison directe; Y signifie un atome d'oxygene, de soufre ou un reste imino ou N-(C1-C4-alkyle)-imino; Z signifie le reste (CR6R7)n, ou n peut etre 0 a 3; R2 signifie un atome d'hydrogene, un reste alkyle avec 1 a 6 atomes de C, eventuellement substitue par un hydroxy ou amino; ou un reste C1-C4-alkoxycarbonyle, cyano ou di-C1-C4-alkylaminocarbonyle; R3, R4, R5, R6, R7 signifient chacun un atome d'hydrogene, un reste alkyle avec 1 a 6 atomes de C, eventuellement substitue par un hydroxy ou amino; ou un reste aryle; R3 et R4 en commun un reste trimethylene, tetramethylene ou 1,3-butadienylene, ceci pour autant que R2 et R5 representent en commun une liaison directe; ce procede utilisant comme compose de depart ceux de la formule generale II (FORMULE) dans laquelle R1,
PCT/DE1981/000225 1980-12-15 1981-12-14 Procede de preparation de n-heterocycles-(alpha)2 Ceased WO1982002046A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3047759801215 1980-12-15
DE19803047759 DE3047759A1 (de) 1980-12-15 1980-12-15 Verfahren zur herstellung von (delta)(pfeil hoch)2(pfeil hoch)-n-heterocyclen

Publications (1)

Publication Number Publication Date
WO1982002046A1 true WO1982002046A1 (fr) 1982-06-24

Family

ID=6119521

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1981/000225 Ceased WO1982002046A1 (fr) 1980-12-15 1981-12-14 Procede de preparation de n-heterocycles-(alpha)2

Country Status (4)

Country Link
EP (1) EP0078804A1 (fr)
JP (1) JPS57501962A (fr)
DE (1) DE3047759A1 (fr)
WO (1) WO1982002046A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0345775A1 (fr) * 1988-06-09 1989-12-13 Yashima Chemical Industrial Co., Ltd. Dérivé d'oxazoline ou de thiazoline
US5478855A (en) * 1992-04-28 1995-12-26 Yashima Chemical Industry Co., Ltd. 2-(2,6-difluorophenyl)-4-(2-ethoxy-4-tert-butylphenyl)-2-oxazoline
US5631014A (en) * 1994-06-09 1997-05-20 Yashima Chemical Industry Co., Ltd. Oxazoline derivatives, insecticidal and miticidal composition, and method for controlling insects and mites
US7049333B2 (en) 2002-06-04 2006-05-23 Sanofi-Aventis Deutschland Gmbh Substituted thiophenes: compositions, processes of making, and uses in disease treatment and diagnosis
US7888513B2 (en) 2005-12-05 2011-02-15 Takasago International Corporation Condensation reaction by metal catalyst
CN114436989A (zh) * 2021-12-24 2022-05-06 江苏维尤纳特精细化工有限公司 一种二噁唑啉制备工艺及装置

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0063538B1 (fr) * 1981-04-13 1986-08-06 Schering Aktiengesellschaft Prostaglandines et prostacyclines, leurs préparations et applications pharmaceutiques
DE3411868A1 (de) * 1984-03-30 1985-10-10 The Dow Chemical Co., Midland, Mich. Herstellung in fluessiger phase von 2-h-2-oxazolinen und 2-substituierten 2-oxazolinen mit einem anorganischen zinksalz
ES2128529T3 (es) * 1993-11-26 1999-05-16 Ube Industries Derivados de oxazolina, procedimiento para su preparacion y composiciones agricolas y horticolas para el control de organismos nocivos que los contienen.

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Journal of the American Chemical Society, Vol. 102, No. 23, 5 November 1980 (Washington, US), M.J. MILLER u.a. "Synthesis of beta-Lactams from Substituted Hydroamic Acids", pages 7026-7032, see pages 7029, 7032 see pages 7029, 7030; cited in the application *
Monatshefte fur Chemie, Vol. 111, No. 5, May 1980, (Wien, AU) L.S. TRIFONOV u.a. '2-Azetidinones from 3-Aminopropanoic Acids and the Ph3P/Br2(I2) Condensation Systems', pages 1117-1123, see the whole document *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0345775A1 (fr) * 1988-06-09 1989-12-13 Yashima Chemical Industrial Co., Ltd. Dérivé d'oxazoline ou de thiazoline
US5478855A (en) * 1992-04-28 1995-12-26 Yashima Chemical Industry Co., Ltd. 2-(2,6-difluorophenyl)-4-(2-ethoxy-4-tert-butylphenyl)-2-oxazoline
US5631014A (en) * 1994-06-09 1997-05-20 Yashima Chemical Industry Co., Ltd. Oxazoline derivatives, insecticidal and miticidal composition, and method for controlling insects and mites
US7049333B2 (en) 2002-06-04 2006-05-23 Sanofi-Aventis Deutschland Gmbh Substituted thiophenes: compositions, processes of making, and uses in disease treatment and diagnosis
US7317033B2 (en) 2002-06-04 2008-01-08 Sanofi-Aventis Deutschland Gmbh Substituted thiophenes: compositions, processes of making, and uses in disease treatment and diagnosis
US7488746B2 (en) 2002-06-04 2009-02-10 Sanofi-Aventis Deutschland Gmbh Substituted thiophenes: compositions, processes of making, and uses in disease treatment and diagnosis
US7763643B2 (en) 2002-06-04 2010-07-27 Sanofi-Aventis Deutschland Gmbh Substituted thiophenes: compositions, processes of making, and uses in disease treatment and diagnosis
US7888513B2 (en) 2005-12-05 2011-02-15 Takasago International Corporation Condensation reaction by metal catalyst
CN114436989A (zh) * 2021-12-24 2022-05-06 江苏维尤纳特精细化工有限公司 一种二噁唑啉制备工艺及装置

Also Published As

Publication number Publication date
JPS57501962A (fr) 1982-11-04
EP0078804A1 (fr) 1983-05-18
DE3047759A1 (de) 1982-07-15

Similar Documents

Publication Publication Date Title
BR9713136A (pt) Composto, composição inseticida, acaricida, ou nematicida, e, processos para combate e controle de pestes de inseto, acarino ou nematóide em um local e para preparação de um composto.
CH629778A5 (de) Verfahren zur herstellung neuer 1,4-dihydropyridinderivate.
DE2416449A1 (de) Penicilline, ihre salze, verfahren zu ihrer herstellung und arzneimittel
HU200465B (en) Process for producing substituted alphaamino acids, derivatives thereof and pharmaceutical compositions comprising such compounds
WO1982002046A1 (fr) Procede de preparation de n-heterocycles-(alpha)2
EP0305322B1 (fr) Dérivés d'isoxazole-bêta-carboline
DE1159462B (de) Verfahren zur Herstellung von s-Triazinderivaten
DE2205745A1 (de) Neue durch den n-cyaniminorest substituierten heterocyclen und verfahren zu ihrer herstellung
DE2828578C2 (de) Thiazolidine, ihre Herstellung sowie Verwendung
DE1239692B (de) Verfahren zur Herstellung von 3-(alpha-Arylalkyl)-sydnoniminen, ihren Salzen und N-Acylderivaten
Hoffmann et al. A simple synthesis of 2, 3-diketo amides from 3-keto amides
DE3730748A1 (de) Neue polyoxygenierte labdanderivate, ein verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
EP0266308B1 (fr) Dérivés de l'indolo-pyrazino-benzodiazépine
EP0234516A1 (fr) Dérivés de la 1,6-naphtyridine, procédé pour leur préparation et médicament les contenant pour le traitement des maladies cardio-vasculaires
CH619468A5 (fr)
DD243277A5 (de) Verfahren zur herstellung neuer 3-phenyl-2-propenamin-derivate
EP0362350A1 (fr) Procede de production d'heteroaromates azotes a 5 membres
EP0202625A2 (fr) Procédé de préparation de l'ester 3-bêta-(N-benzyl-N-méthylamino)-éthyl 5-méthylde l'acide 2,6-diméthyl-4-(3'-nitrophényl)-1,4-dihydropyridine-3,5-dicarboxylique et son sel hydrochlorique
DE3423105A1 (de) Verfahren zur herstellung optisch aktiver 1,4-dihydropyridine
US4584313A (en) (Substituted-phenyl)-5-oxo-2-pyrrolidinepropanoic acids and esters thereof, and use for reversing electroconvulsive shock-induced amnesia
DE3111025A1 (de) "aminosaeurederivate, deren herstellung und deren verwendung als arzneimittel"
EP0334147A1 (fr) Pyrroles disubstitués
CH634555A5 (de) Verfahren zur herstellung von mit nocardicin verwandten azetidinonen.
EP0607802B1 (fr) Procédé pour la préparation d'une mélange de dinitriles de l'acide glutaconique aminométhylènés
DE2747121A1 (de) 6-(m-aminophenyl-2,3,5,6-tetrahydroimidazo eckige klammer auf 2,1-b eckige klammer zu thiazolderivate, verfahren zu ihrer herstellung und ihre verwendung

Legal Events

Date Code Title Description
AK Designated states

Designated state(s): JP US

AL Designated countries for regional patents

Designated state(s): AT BE CH DE FR GB LU NL SE