WO1999065857A1 - Katalytisch titan(iv)-oxid vermittelte geminale unsymmetrische dialkylierung von carbonsäureamiden - Google Patents
Katalytisch titan(iv)-oxid vermittelte geminale unsymmetrische dialkylierung von carbonsäureamiden Download PDFInfo
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- WO1999065857A1 WO1999065857A1 PCT/EP1999/004249 EP9904249W WO9965857A1 WO 1999065857 A1 WO1999065857 A1 WO 1999065857A1 EP 9904249 W EP9904249 W EP 9904249W WO 9965857 A1 WO9965857 A1 WO 9965857A1
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- dioxide
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- metal
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/66—Preparation of compounds containing amino groups bound to a carbon skeleton from or via metallo-organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/023—Preparation; Separation; Stabilisation; Use of additives
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0231—Halogen-containing compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0272—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255
- B01J31/0274—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255 containing silicon
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0272—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255
- B01J31/0275—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255 also containing elements or functional groups covered by B01J31/0201 - B01J31/0269
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
- B01J21/06—Silicon, titanium, zirconium or hafnium; Oxides or hydroxides thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
- B01J21/06—Silicon, titanium, zirconium or hafnium; Oxides or hydroxides thereof
- B01J21/063—Titanium; Oxides or hydroxides thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
- B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
- B01J2231/341—1,2-additions, e.g. aldol or Knoevenagel condensations
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
Definitions
- the present invention relates to a method for asymmetrical disubstitution of carboxamides on the geminal carbonyl carbon atom by means of Grignard reagents in the presence of titanium dioxide and the compounds of the general formula (I) prepared by this method
- H, A, Ar, -Si (R 6 ) 3 , -Sn (R 6 ) 3 , -SR 7 , -OR 7 , -NR 8 R 9 or R 1 and R 2 or R 1 and R 3 or R 8 and R 9 can be connected to one another and together form a cyclic ring with 3 to 8 carbon atoms, which optionally contains, in addition to nitrogen, at least one further heteroatom selected from the group -S-, -O- and -NR 6 -,
- R 4 and R 5 are different and independently of one another A, Ar,
- R 8 and R 9 have the meanings given or R 8 and R 9 or R 4 and
- R 5 can be connected to one another and together form a cyclic ring with 3 to 8 C atoms, which optionally also has at least one hetero atom selected from the group -S-,
- -O- and -NR 6 - may contain;
- R 6 , R 7 , R 8 and R 9 independently of one another A or Ar
- A is a straight-chain or branched alkyl radical with 1 to 10 C-
- Atoms straight-chain or branched alkenyl radical with 2 to 10 carbon atoms, or straight-chain or branched alkynyl radical with 2-10 carbon atoms or substituted or unsubstituted cycloalkyl radical with 3-8 carbon atoms, mono- or polyunsaturated cycloalkyl radical with 3-8 carbon atoms and
- Ar is a substituted or unsubstituted aryl radical with 6-20 C
- R 2 or R 1 and R 3 or R 8 and R 9 can be connected to one another and together form a cyclic ring with 3 to 8 C atoms, which optionally also has at least one further heteroatom selected from the group -S-, -O- and -NR 6 - contains,
- R 4 and R 5 independently of one another A, Ar, -Si (R 6 ) 3 , -Sn (R 6 ) 3 , -SR 7 , - OR 7 , -NR 8 R 9 , where R 8 and R 9 have the meanings given have or R 8 and R 9 or R 4 and R 5 can be connected to one another and together form a cyclic ring having 3 to 8 C atoms, which optionally also has at least one hetero atom selected from the group -S-, -O in addition to a nitrogen atom - and -NR 6 - may contain;
- R 6 , R 7 , R 8 and R 9 independently of one another A or Ar
- A is a straight-chain or branched alkyl radical with 1 to 10 carbon atoms, straight-chain or branched alkenyl radical with 2 to
- R 1 , R 2 and R 3 have the meanings given for formula (I), by reaction with a nucleophilic reagent of the general form (lilac) and (IIIb) or a nucleophilic reagent of the general formula (IIIc)
- R 4 and R 5 have the meaning given for formula (I), and
- the process is carried out in the presence of catalytic amounts of a metal oxide selected from the group consisting of titanium dioxide, zirconium dioxide and hafnium dioxide.
- the invention also relates to a corresponding process which is carried out in the presence of a cocatalyst.
- the present invention therefore also includes a process in which metal isopropylates and alkylsilyl halides are used as cocatalysts; namely metal isopropylates of the general formula (IV) and alkylsilyl halides of the general formula (V)
- M 'AI Ca, Na, K, Si or Mg, preferably Mg or Na
- s is an integer from 1 to 4 and the oxidation state of the metal
- R 4 , R and X have the meanings given above
- carboxamides of the general formula (II) can be reacted with good yields in the process described here, in which R 1 , R 2 and R 3 can independently assume the following meanings:
- a ie branched or unbranched alkyl having 1 to 10 carbon atoms such as methyl, ethyl, n- or i-propyl, n-, sec- or t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and their suitable Isomers, or cycloalkyl with 3-8 C atoms, such as cyciopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or corresponding methyl- or ethyl-substituted cycloalkyl groups or mono- or polyunsaturated cycloalkyl groups, such as cyclopentenyl or cyclopentadienyl or branched or unbranched alkenyl having 2 to 10 C atoms, such as allyl, vinyl, isoprop
- Aralkenyl or aralkynyl where in each case the aryl, alkenyl and alkynyl group can assume the given meanings, such as in phenylethynyl.
- R 4 and R 5 preferably represent an alkyl radical having 1 to 10 carbon atoms, such as methyl, ethyl, n- or i-propyl, n-, sec- or t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, Decyl and its suitable isomers, or cycloalkyl with 3-8 C atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or corresponding methyl- or ethyl-substituted cycloalkyl groups or mono- or polyunsaturated cycloalkyl groups, such as cyclopentenyl or cyclopentadienyl or branched or unbranched alkenyl with 2 to 10 C atoms, such as allyl, vinyl, isopropenyl,
- aryl radicals with 6 to 20 C atoms optionally unsubstituted or mono- or polysubstituted, such as phenyl, naphthyl, anthryl, phenanthryl, monosubstituted or polysubstituted by substituents selected from the group NO 2 , F, Cl, Br, NH 2 , NHA, NA 2 , OH and OA, where A can have the meanings given above, can be single, multiple or fully halogenated, preferably fluorinated, or
- aralkyl radicals with 7 to 20 carbon atoms such as benzyl
- substituents selected from the group NO 2 , F, Cl, Br, NH 2 , NHA, NA 2 , OH and OA, where A is the can have meanings given above, can be single, multiple or fully halogenated, preferably fluorinated
- radicals R 4 and R 5 in the general formula (IIIc) can represent an alkyl having 2-7 C atoms, so that the reaction according to the invention gives a compound of the general formula (I) in which the radicals R 4 and R 5 form a cyclic ring with 3 to 8 atoms.
- R 4 and R 5 particularly preferably have the meaning of a
- Alkyl radicals e.g. Methyl, ethyl, n- or i-propyl, n-, sec- or t-butyl, pentyl, hexyl, one or cycloalkyl, e.g. Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or an aryl radical, such as e.g. Phenyl, or an aralkyl radical, e.g. Benzyl.
- the radical Z in the general formulas (purple) and (IIIb) preferably represents a radical MgX with X for Cl or Br or the radical Z for lithium.
- the radical X in the general formula (IIIc) preferably represents Cl or Br.
- Grignard compounds such as: methyl magnesium bromide, ethyl magnesium bromide, n- or i-propyl magnesium bromide, i-, sec- or tert-butyl magnesium bromide, n-hexyl magnesium bromide, cyclohexyl magnesium chloride, are particularly preferred,
- Metal isopropylates and alkylsilyl halides are suitable as cocatalysts in this reaction. These are in particular metal isopropylates of the general formula (IV) and alkylsilyl halides of the general formula (V)
- M 'AI Ca, Na, K, Si or Mg, preferably Mg or Na
- s is an integer from 1 to 4 and the oxidation state of the metal
- Metal isopropylates are preferably used, in which s is an integer from 1 to 4 and the oxidation state of the metal and M 'is AI, Ca, Na, K, Si or Mg. Mg or Na are particularly preferred.
- Alkylsilyl halides in which R denotes alkyl having 1 to 6 C atoms are preferably used. Those in which R is alkyl with 1 to 3 C atoms and X is chlorine are particularly preferred.
- silicon compounds are suitable as cocatalysts:
- metal dioxide selected from the group consisting of titanium dioxide, zirconium dioxide and hafnium dioxide
- metal dioxide selected from the group consisting of titanium dioxide, zirconium dioxide and hafnium dioxide
- Powdered titanium (IV) dioxide is preferably used. In the simplest case, this can be a technical quality. In order to be able to ensure simple separation after the reaction has taken place, it is advantageous to choose a quality which is not too finely divided.
- the pre-dried metal dioxide preferably titanium dioxide, is used as a suspension in a suitable, pre-dried solvent. Suitable solvents are e.g. aliphatic or aromatic hydrocarbons or ethers.
- Solvents selected from the group consisting of toluene, THF, n-hexane, benzene and diethyl ether are preferably used, which are dried before the reaction by methods known to the person skilled in the art. Drying can be done with
- Magnesium sulfate, calcium chloride, sodium, potassium hydroxide or other methods can be used.
- a preferred embodiment of the process according to the invention is that the titanium dioxide used as catalyst in an amount of 1 to 15, preferably 1, 5 to 14, in particular 2 to 10, and very particularly preferably 3 to 6 mol%, based on one mol of the amide used as starting material is presented in the form of a suspension which is adjusted to a temperature of 10 to 30 ° C., preferably to 15-25 ° C., particularly preferably to a temperature of about 20 ° C.
- the starting material is either as such in liquid form or dissolved in a solvent, selected from the group toluene, THF, n-hexane, benzene and diethyl ether slowly added dropwise with stirring. Then one of the amount of cocatalyst to be reacted, if necessary also in a solvent, is added dropwise.
- the reaction mixture obtained is stirred for a short time, ie for a few minutes, at a constant temperature.
- a mixture consisting of equal amounts of two different Grignard reagents is then slowly added to the reaction mixture thus obtained such that a substitution of the geminal carbonyl carbon atom by two different substituents, i. H. thus an asymmetrical substitution of the geminal carbonyl carbon atom can take place.
- the addition of the nucleophilic reagents according to the invention should take place so slowly that the temperature of the reaction mixture does not exceed 50.degree. It is advantageous if the addition of the nucleophilic reagents, i. H. the Grignard reagents or the lithium compounds are mixed thoroughly, preferably with vigorous stirring.
- the nucleophilic reagents used preferably Grignard reagents, are added in an amount of 1.05 to 1.5 moles per mole of reactant reactant.
- the Grignard reagents are preferably added in an amount of 1.1 to 1.3 mol, based on 1 mol of starting material. If a nucleophilic reagent or Grignard reagent of the general formula (IIIc) is used, it is added to the reaction solution corresponding to twice the number of reactive groups, only in equimolar amounts based on the starting material.
- the reaction mixture is stirred for a while at a constant temperature until the reaction is complete.
- the Grignard reagents are prepared in situ by reacting magnesium with a compound of the general formula (purple ') and (IIIb') or (IIIc '), in which R 4 , R 5 and X have the meanings given above.
- the general formula (purple ') and (IIIb') or (IIIc ') have the meanings given above.
- the amount of magnesium is 2 to 5 times the molar amount, preferably 2.8 to 3.2 times the molar amount, based on the compounds of the general formula (II) used as starting material and the amount of the compound of the general formula (lilac '), (lllb') and (lllc ') 1 to 1.9 times the molar amount, preferably 1.1 to 1.3 times the molar amount based on the compound of the general formals (II).
- asymmetrically substituted amino compounds of the general formula (I) can be prepared with good or satisfactory yields within reasonable reaction times.
- the reaction times can be considerably shortened, in the best case to one hour, without thereby reducing the yields achieved to have to.
- a catalyst system consisting of a metal dioxide, selected from the group consisting of titanium dioxide, zirconium dioxide and hafnium dioxide, as a catalyst and a compound of the general formulas (IV), (V) or (VI) with the meanings given above is also an object of the present invention .
- this catalyst system in the preparation of the asymmetrically substituted compounds of the general formula (I).
- reaction mixture can be worked up in a manner known to the person skilled in the art.
- the products can be used as salts with the help of hydrochloric acid solutions such.
- hydrochloric acid solutions such.
- a suitable amount of saturated ammonium chloride solution and water can be added and stirring is continued intensively for several hours (1-3 hours).
- the resulting precipitate is separated off and washed with a little ether, preferably diethyl ether.
- the filtrate is made basic (pH> 10) by adding a suitable alkali, such as a NaOH, KOH, sodium or potassium carbonate solution, preferably sodium hydroxide solution.
- a suitable alkali such as a NaOH, KOH, sodium or potassium carbonate solution, preferably sodium hydroxide solution.
- the phases that form are then separated and the aqueous phase is extracted several times (e.g. three times with 30 ml each in the above special case) with diethyl ether.
- the combined organic phases are washed with (e.g. 15 ml) saturated sodium chloride solution and can be dried over potassium carbonate, magnesium sulfate or sodium sulfate and filtered.
- the products can be purified in various ways by methods known to those skilled in the art, e.g. in the following way:
- the organic phase is washed several times with a 0.5 M acid solution, preferably an aqueous hydrochloric acid solution, extracted.
- the extract obtained is adjusted to pH> 10 using lyes, preferably 2 M sodium hydroxide solution, and extracted at least once, preferably several times, with diethyl ether.
- the organic phases obtained in this way, which contain the reaction product, can optionally be dried over potassium carbonate, magnesium sulfate or sodium sulfate and freed from the organic solvent under vacuum.
- the Grignard reagents can also be replaced by the corresponding lithium compounds.
- the corresponding lithium compounds like the Grignard compounds, can be prepared according to methods generally known to those skilled in the art and can be reacted according to the invention in the same manner as described above.
- the compounds of general formula (I) prepared according to the invention can, for. B. as intermediates for the production of sulfur- or selenium-containing amines for the chiral catalysis of diethylzinc syntheses (literature: Werth, Thomas; Tetrahedron Lett. 36; 1995, 7849-7852, Werth, Thomas et all. Helv. Chim. Acta 79, 1996, 1957-1966) can be used.
- Titanium (IV) oxide induced asymmetrical dialkylation of carboxamides with two different Grignard reagents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99932701A EP1087932A1 (de) | 1998-06-18 | 1999-06-18 | Katalytisch titan(iv)-oxid vermittelte geminale unsymmetrische dialkylierung von carbonsäureamiden |
JP2000554684A JP2002518360A (ja) | 1998-06-18 | 1999-06-18 | カルボキサアミドの触媒酸化チタン(iv)誘導性ジェミナル不斉ジアルキル化 |
KR1020007014273A KR20010052917A (ko) | 1998-06-18 | 1999-06-18 | 산화 티탄(4) 촉매에 의해 매개된 카복실산 아미드의동일탄소상 비대칭적 디알킬화 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19827165A DE19827165A1 (de) | 1998-06-18 | 1998-06-18 | Katalytisch Titan(IV)-oxid-vermittelte geminale unsymmetrische Dialkylierung von Carbonsäureamiden |
DE19827165.4 | 1998-06-18 |
Publications (1)
Publication Number | Publication Date |
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WO1999065857A1 true WO1999065857A1 (de) | 1999-12-23 |
Family
ID=7871279
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1999/004249 WO1999065857A1 (de) | 1998-06-18 | 1999-06-18 | Katalytisch titan(iv)-oxid vermittelte geminale unsymmetrische dialkylierung von carbonsäureamiden |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1087932A1 (de) |
JP (1) | JP2002518360A (de) |
KR (1) | KR20010052917A (de) |
DE (1) | DE19827165A1 (de) |
WO (1) | WO1999065857A1 (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001044160A2 (de) * | 1999-12-14 | 2001-06-21 | Merck Patent Gmbh | Verfahren zur herstellung kombinatorischer aminbibliotheken |
-
1998
- 1998-06-18 DE DE19827165A patent/DE19827165A1/de not_active Withdrawn
-
1999
- 1999-06-18 KR KR1020007014273A patent/KR20010052917A/ko not_active Application Discontinuation
- 1999-06-18 WO PCT/EP1999/004249 patent/WO1999065857A1/de not_active Application Discontinuation
- 1999-06-18 JP JP2000554684A patent/JP2002518360A/ja active Pending
- 1999-06-18 EP EP99932701A patent/EP1087932A1/de not_active Withdrawn
Non-Patent Citations (7)
Title |
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"HOUBEN-WEYL, METHODEN DER ORGANISCHEN CHEMIE, vol. XI/1, S. 820-823", 1957, GEORG THIEME VERLAG, STUTTGART, DE, XP002117680 * |
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN., vol. 66, no. 6, 1993, JAPAN PUBLICATIONS TRADING CO. TOKYO., JP, pages 1699 - 1702, ISSN: 0009-2673 * |
CHEMICAL ABSTRACTS, vol. 120, no. 7, 14 February 1994, Columbus, Ohio, US; abstract no. 76866d, KUNO HIDEYUKI ET AL.: "Oxidation of alcohols to aldehydes and ketones over zirconium (IV) oxide modified by trimethylsilyl chloride" page 838; column 2; XP002117682 * |
JERRY MARCH: "Advanced organic chemistry, third Editition", 1985, JOHN WILEY & SONS, NEW YORK . CHICHESTER . TORNTO . SINGAPORE, XP002117733 * |
KUFFNER F. ET AL.: "Über hochverzweigte aliphatische Verbindungen", MONATSHEFTE FÜR CHEMIE, vol. 93, 1962, pages 496 - 475, XP002117676 * |
VLADIMIR CHAPLINSKI ET AL.: "A new versatile reagent for the synthesis of cyclopropylamines...", SYNLETT., 1997, THIEME VERLAG, STUTTGART., DE, pages 111 - 114, XP002117679, ISSN: 0936-5214 * |
YUYING C. HWANG ET AL.: "A synthesis of &-substituted amines", JOURNAL OF ORGANIC CHEMISTRY., vol. 50, no. 20, 1985, EASTON US, pages 3885 - 3890, XP002117673 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001044160A2 (de) * | 1999-12-14 | 2001-06-21 | Merck Patent Gmbh | Verfahren zur herstellung kombinatorischer aminbibliotheken |
WO2001044160A3 (de) * | 1999-12-14 | 2002-03-07 | Merck Patent Gmbh | Verfahren zur herstellung kombinatorischer aminbibliotheken |
Also Published As
Publication number | Publication date |
---|---|
EP1087932A1 (de) | 2001-04-04 |
KR20010052917A (ko) | 2001-06-25 |
DE19827165A1 (de) | 1999-12-23 |
JP2002518360A (ja) | 2002-06-25 |
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