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WO1998013319A1 - Nouvelles compositions de reduction et leurs procedes de fabrication - Google Patents

Nouvelles compositions de reduction et leurs procedes de fabrication Download PDF

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Publication number
WO1998013319A1
WO1998013319A1 PCT/US1997/017191 US9717191W WO9813319A1 WO 1998013319 A1 WO1998013319 A1 WO 1998013319A1 US 9717191 W US9717191 W US 9717191W WO 9813319 A1 WO9813319 A1 WO 9813319A1
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WO
WIPO (PCT)
Prior art keywords
slurry
composition
additive
lewis base
mole
Prior art date
Application number
PCT/US1997/017191
Other languages
English (en)
Inventor
Anne Pautard-Cooper
Eric John Granger
Philip F. Sims
James A. Schwindeman
John Francis Engel
Terry Lee Rathman
Original Assignee
Fmc Corporation
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 Fmc Corporation filed Critical Fmc Corporation
Priority to AU46514/97A priority Critical patent/AU4651497A/en
Publication of WO1998013319A1 publication Critical patent/WO1998013319A1/fr

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Classifications

    • E—FIXED CONSTRUCTIONS
    • E04—BUILDING
    • E04H—BUILDINGS OR LIKE STRUCTURES FOR PARTICULAR PURPOSES; SWIMMING OR SPLASH BATHS OR POOLS; MASTS; FENCING; TENTS OR CANOPIES, IN GENERAL
    • E04H12/00—Towers; Masts or poles; Chimney stacks; Water-towers; Methods of erecting such structures
    • E04H12/22—Sockets or holders for poles or posts
    • E04H12/2292—Holders used for protection, repair or reinforcement of the post or pole
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B6/00—Hydrides of metals including fully or partially hydrided metals, alloys or intermetallic compounds ; Compounds containing at least one metal-hydrogen bond, e.g. (GeH3)2S, SiH GeH; Monoborane or diborane; Addition complexes thereof
    • C01B6/24—Hydrides containing at least two metals; Addition complexes thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B31/00—Reduction in general
    • 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
    • C07D295/027—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 containing only one hetero ring
    • C07D295/03—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 containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
    • E—FIXED CONSTRUCTIONS
    • E04—BUILDING
    • E04C—STRUCTURAL ELEMENTS; BUILDING MATERIALS
    • E04C5/00—Reinforcing elements, e.g. for concrete; Auxiliary elements therefor
    • E04C5/01—Reinforcing elements of metal, e.g. with non-structural coatings
    • E04C5/06—Reinforcing elements of metal, e.g. with non-structural coatings of high bending resistance, i.e. of essentially three-dimensional extent, e.g. lattice girders

Definitions

  • This invention relates to novel compositions for reduction of organic substrates, and processes for preparing and using the same .
  • Lithium aluminum hydride (LiAlH 4 ) is a powerful reducing agent, soluble in organic solvents, and has found wide utility in organic synthesis.
  • a wide variety of functional groups are reduced with this reagent, including aldehydes, ketones, esters, amides, epoxides, nitriles and imides.
  • the expense of lithium aluminum hydride prevents its wider industrial employment .
  • compositions prepared from an active hydride, an additive, and a Lewis base can provide a superior reducing system for organic substrates .
  • a composition prepared from 60 mole % tetrahydrofuran as the Lewis base, 10 mole % lithium chloride as the additive, 10 mole % sodium aluminum hydride as the active hydride, and 20 mole % toluene can afford excellent yields in standard organic reductions.
  • the compositions of the invention are non- pyrophoric and are more thermally stable than pure THF solutions of sodium aluminum hydride (NaAlH 4 ) or lithium aluminum hydride (LiAlH 4 ) .
  • novel compositions of the invention can be prepared by initially adding the Lewis base to the additive.
  • the hydride species can then be added, optionally in the hydrocarbon solvent.
  • the mixture can then be optionally heated to the reflux temperature (or less) , typically from about thirty minutes to about four hours .
  • the present invention also provides processes for the reduction of organic substrates using the compositions of the invention.
  • active hydrides including metal hydrides such as sodium aluminum hydride, trisodium aluminum hexahydride, and the like and mixtures thereof can be employed as the active hydride component .
  • useful additives include, but are not limited to, lithium chloride, lithium bromide, aluminum trichloride, titanium tetrachloride, titanium tetrabromide , lithium alkoxides, lithium alkoxides of chiral alcohols (such as menthol), lithium dialkyla ides , lithium dialkyl amides of chiral amines (such as (+) bis-[(R)-l- phenethyl] a ine) , and the like and mixtures thereof.
  • useful hydrocarbon solvents include, but are not limited to, pentane, hexane, heptane, cyclohexane, decane, toluene, xylenes, ethylbenzene , cumene, cymene, and the like and mixtures thereof.
  • Lewis bases examples include, but are not limited to, tetrahydrofuran, 2 -methyltetrahydrofuran, diethyl ether, dibutyl ether, methyl t-butyl ether (MTBE) , 1,2- diethoxyethane, 1 , 2-dimethoxyethane, triethylamine, tributylamine, N, N, N' , N' - tetramethylethylenediamine (TMEDA) , diisopropylethylamine , and the like and mixtures thereof .
  • Typical concentrations (mole %) of the components used to prepare the reducing composition of the invention are listed in the table below. COMPONENT MINIMUM MAXIMUM Lewis Base 45 80
  • novel compositions of the invention can be prepared by initially adding the Lewis base to the additive.
  • the hydride species can then be added, optionally in the hydrocarbon solvent.
  • the mixture can then be optionally heated to the reflux temperature (or less) for a few hours, typically from about thirty minutes to about four hours.
  • the novel composition is prepared by adding a slurry of sodium aluminum hydride/toluene to a slurry of lithium chloride/tetrahydrofuran . Because the addition is very exothermic, care should be taken. When using the specific reagents sodium aluminum hydride and lithium chloride, the reagents must be combined in a precise manner to result in reduction product yields comparable to that of lithium aluminum hydride. Otherwise, reduction product yields comparable to that of sodium aluminum hydride result .
  • the composition of the invention is also unique as it is prepared from a slurry of sodium aluminum hydride in hydrocarbon solvent (i.e., about 80 weight percent (wt%) or less sodium aluminum hydride) and a minimal amount of tetrahydrofuran, in contrast to solid or damp cake forms of sodium aluminum hydride .
  • the slurry can be a commercially available slurry of 40 wt% sodium aluminum hydride in toluene.
  • a hydrocarbon solvent alone, such as toluene without a Lewis base, such as tetrahydrofuran, can hinder the preparation of this effective, novel composition.
  • composition of the invention can include starting materials, counterion exchange products, complexes of starting materials and/or counterion exchange products, and mixtures thereof.
  • the novel reduction composition of this invention can also be characterized by its particle size distribution.
  • typical particle size distribution of a novel reduction composition in accordance with the invention prepared from 56.9 mole % tetrahydrofuran as the Lewis base, 15.7 mole % lithium chloride as the additive, 12.6 mole % sodium aluminum hydride as the active hydride, and 14.8 mole % toluene was determined on a Malvern MasterSizer.
  • the mean diameter for the reduction composition is around 350 ⁇ m and the median is 400 ⁇ m.
  • the particle size distribution of sodium aluminum hydride exhibits a mean diameter at 216 ⁇ m and a median at 200 ⁇ m .
  • the particle size distribution of lithium chloride exhibits a mean diameter at 424 ⁇ m and a median at 448 ⁇ m.
  • the thermal behavior of the novel reduction composition was studied in an RSST (Reactive System Screening Tool) and found to be more thermally stable than 10 wt% LiAlH 4 /THF or 40 wt% NaAlH, .
  • the L ⁇ AlH 4 /THF solution was found to produce a runaway reaction represented by a rapid rate acceleration when heated above 130°C.
  • a NaAlH trap/THF solution was found to produce a runaway reaction represented by a rapid rate acceleration when heated above 220 °C.
  • the organic compound to be reduced is added to the reduction composition of the invention under an inert atmosphere.
  • the reduction composition can be added to the organic substrate, or the reduction composition and organic substrate added simultaneously.
  • the reduction reaction proceeds under appropriate conditions at a temperature sufficient and for a time sufficient for the reduction reaction to proceed, generally at a temperature of about ambient to about the reflux temperature of the mixture for about one hour to about 24 hours.
  • the reaction can be terminated by quenching the mixture, for example, by addition of water and aqueous NaOH and cooling. Work-up of the reduction reaction mixture and isolation of the reduced product can be accomplished using conventional procedures known in the art .
  • compositions of the invention can be used for the reduction of a variety of organic compounds including without limitation aldehydes, ketones, esters, amides, epoxides, nitriles, and other imides.
  • Exemplary compounds which can be reduced in accordance with the invention include (+/-) trans 3 -ethoxycarbonyl-4 - (4 ' - fluorophenyl) -N-methyl-piperidine-2 , 6-dione (to (+/-) t ran s 4- (4' -fluorophenyl) -3 -hydroxymethyl-N- methylpiperidine) , N-methylsuccinimide, ethyl 1- methylnipecotate, and the like.
  • the inventors have found that the reactivity of sodium aluminum hydride can be improved by the addition of various additives.
  • reductions can be accomplished with sodium aluminum hydride when its activity is modified with various additives as described above.
  • the additive lithium chloride could be mixed with sodium aluminum hydride in order to produce a resulting hydride composition that performs as well as lithium aluminum hydride alone .
  • LiCl can be reacted with aAlHj j in stoichiometric amounts to form lithium aluminum hydride, which is then separated from the by-product, NaCl , prior to use.
  • This metathesis reaction requires the addition of a catalyst, such as a small amount of LiAlH 4 , to initiate the reaction, or alternatively a NaAlH 4 solution forming prestep.
  • a catalyst such as a small amount of LiAlH 4
  • LiCl can be added in less than stoichiometric amounts, and without requiring LiAlH 4 as a catalyst, or a NaAlH 4 solution forming prestep.
  • the starting compounds include sodium aluminum hydride and lithium chloride
  • the order of addition of the additive is important. However, it is not currently believed that the order of addition of the additives is critical when using other starting materials, in which case it is currently believed that the additives can be added at various times during the entire reduction.
  • LiAlH 4 is much more expensive than NaAlH 4 .
  • a 500 ml., three-necked round-bottom flask was fitted with a mechanical stirrer, a Teflon ® stopper, and a Claisen adapter fitted with a dry ice condenser, a Teflon ® clad thermocouple, and an argon inlet.
  • This apparatus was dried in an oven overnight at 125°C, assembled hot, and allowed to cool to room temperature in a stream of argon.
  • the flask was charged with 10.00 grams (0.237 mole) of anhydrous lithium chloride, and 70 ml. of tetrahydrofuran. The resultant slurry was stirred at 350 RPMs . A slight exotherm, 3°C, was observed.
  • This slurry was prepared from 15.3 mole % lithium chloride, 56.1 mole % tetrahydrofuran, 13.9 mole % sodium aluminum hydride, and 14.7 mole % toluene.
  • the dark gray slurry was employed in a reduction after stirring at room temperature for one hour .
  • a 500 ml., three-necked, jacketed, round-bottom flask was fitted with a mechanical stirrer, a Teflon ® stopper, and a Claisen adapter fitted with a dry ice condenser, a Teflon ® clad thermocouple, and an argon inlet .
  • This apparatus was dried in an oven overnight at 125°C, assembled hot, and allowed to cool to room temperature in a stream of argon.
  • the flask was charged with 13.80 grams (0.327 mole) of anhydrous lithium chloride, and 97 ml. of tetrahydrofuran. The resultant slurry was stirred at 350 RPMs . A slight exotherm, 3°C, was observed.
  • This slurry was stirred at less than 10°C for one hour, then allowed to gradually warm to ambient temperature overnight .
  • This slurry was prepared from 15.5 mole % lithium chloride, 56.8 mole % tetrahydrofuran, 10.9 mole % sodium aluminum hydride, and 16.9 mole % toluene.
  • the dark gray slurry was employed in a reduction after stirring at room temperature overnight .
  • This slurry was prepared from 15.3 mole % lithium chloride, 56.1 mole % tetrahydrofuran, 13.9 mole % sodium aluminum hydride, and 14.7 mole % toluene.
  • the dark gray slurry was employed in a reduction after stirring at 70°C for two hours.
  • a 500 ml., three-necked, jacketed flask was equipped with a mechanical stirrer, a 125 ml. pressure- equalizing addition funnel, and a Claisen adapter fitted with a Teflon ® clad thermocouple, a dry ice condenser, and an argon inlet .
  • This apparatus was dried in an oven overnight at 125°C, assembled hot, and allowed to cool to room temperature in a stream of argon.
  • the flask was charged with tetrahydrofuran, 70 ml. This solution was stirred at 350 RPMs and cooled to 0°C with a circulating chiller.
  • the feed rate was adjusted to maintain the reaction temperature at 10-15°C. Total imide-ester feed time was 62 minutes. After the end of the feed, the reaction mixture was heated to 65°C for two hours, then recooled to 0°C. Additional toluene, 85 ml., was added. This was followed by slow addition of 9 ml . of water. The reaction mixture got very thick at the end of this addition. Aqueous sodium hydroxide, 15%, 9 ml., was then added dropwise. The solid started to break up at the end of this addition. Water, 9 ml., was then added dropwise. At the end of this feed, the reaction mixture was warmed to 65°C.
  • the reaction mixture was stirred at 65°C for thirty minutes, recooled to 27°C, then the solids were collected on a B ⁇ chner funnel .
  • the solids were reslurried with toluene (2 X 30 ml . ) .
  • the filtrate was two layers. It was concentrated on the rotary evaporator to 250 ml . , and transferred to a separatory funnel.
  • the mixture was diluted with water
  • a 500 ml., four-necked, round bottom flask was equipped with a mechanical stirrer, a 125 ml. pressure- equalizing addition funnel, a Teflon ® stopper and a Claisen adapter fitted with a Teflon ® clad thermocouple, a dry ice condenser, and an argon inlet.
  • This apparatus was dried in an oven overnight at 125°C, assembled hot, and allowed to cool to room temperature in a stream of argon.
  • Lithium chloride 9.85 grams (2.64 equivalents, 232.36 mmole) was added. The flask was then charged with tetrahydrofuran, 67 ml. This solution was stirred at 350 RPMs.
  • the feed rate was adjusted to maintain the reaction temperature at 10-15°C. After the end of the feed, the 250 ml. flask was rinsed with additional toluene, 7 ml, and this was added to the addition funnel. The reaction mixture was heated to 75°C for three hours, then recooled to 10°C. Additional toluene, 50 ml., was added. The speed of the agitator was increased to 500 RPMs. This was followed by slow addition of 9 ml. of water. The reaction mixture got very thick at the end of this addition. Aqueous sodium hydroxide, 15%, 9 ml., was then added dropwise. The solid started to break up at the end of this addition. Water, 18 ml., was then added dropwise.
  • reaction mixture was warmed to 65°C for twenty minutes and the stirrer was slowed to 350 RPMs .
  • the reaction mixture was then cooled to 40°C, then the solids were collected on a Buchner funnel.
  • the solids were reslurried with toluene (2 X 31 ml . ) .
  • the desired product was isolated by precipitation from the combined filtrates, washed, air dried, then dried in a vacuum desiccator overnight .

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Architecture (AREA)
  • Inorganic Chemistry (AREA)
  • Civil Engineering (AREA)
  • Structural Engineering (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention porte sur la préparation de nouvelles compositions de réduction à partir d'un hybride actif, d'un additif et d'une base de Lewis dans un solvant d'hydrocarbure. Ces compositions peuvent fournir un meilleur système de réduction à des substrats organiques.
PCT/US1997/017191 1996-09-24 1997-09-23 Nouvelles compositions de reduction et leurs procedes de fabrication WO1998013319A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU46514/97A AU4651497A (en) 1996-09-24 1997-09-23 Novel reduction compositions and processes for making the same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2652296P 1996-09-24 1996-09-24
US60/026,522 1996-09-24

Publications (1)

Publication Number Publication Date
WO1998013319A1 true WO1998013319A1 (fr) 1998-04-02

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PCT/US1997/017191 WO1998013319A1 (fr) 1996-09-24 1997-09-23 Nouvelles compositions de reduction et leurs procedes de fabrication

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AU (1) AU4651497A (fr)
WO (1) WO1998013319A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1273554A2 (fr) * 2001-05-11 2003-01-08 Rohm And Haas Company Procédé de production d'hydrure de lithium-aluminium à partir d'hydrure de sodium-aluminium
RU2680491C1 (ru) * 2018-04-20 2019-02-21 Акционерное общество "Государственный Ордена Трудового Красного Знамени научно-исследовательский институт химии и технологии элементоорганических соединений" (АО "ГНИИХТЭОС") Способ получения кристаллического литийалюминийгидрида в среде н-дибутилового эфира

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB820513A (en) * 1956-12-21 1959-09-23 Ici Ltd Improvements in and relating to the production of lithium aluminium hydride
FR1245361A (fr) * 1959-02-24 1960-11-04 Ethyl Corp Procédé de préparation d'hydrures d'aluminium
US4902801A (en) * 1985-08-10 1990-02-20 Beecham Group Plc. Process for preparing aryl-piperidine carbinols and novel intermediates used in the process
WO1997006097A1 (fr) * 1995-08-09 1997-02-20 Fmc Corporation Procede d'elaboration d'hydrure de lithium et d'aluminium dans des solvants etheres
WO1997005879A1 (fr) * 1995-08-03 1997-02-20 Fmc Corporation Reductions au moyen d'hydrures

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB820513A (en) * 1956-12-21 1959-09-23 Ici Ltd Improvements in and relating to the production of lithium aluminium hydride
FR1245361A (fr) * 1959-02-24 1960-11-04 Ethyl Corp Procédé de préparation d'hydrures d'aluminium
US4902801A (en) * 1985-08-10 1990-02-20 Beecham Group Plc. Process for preparing aryl-piperidine carbinols and novel intermediates used in the process
WO1997005879A1 (fr) * 1995-08-03 1997-02-20 Fmc Corporation Reductions au moyen d'hydrures
WO1997006097A1 (fr) * 1995-08-09 1997-02-20 Fmc Corporation Procede d'elaboration d'hydrure de lithium et d'aluminium dans des solvants etheres

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1273554A2 (fr) * 2001-05-11 2003-01-08 Rohm And Haas Company Procédé de production d'hydrure de lithium-aluminium à partir d'hydrure de sodium-aluminium
EP1273554A3 (fr) * 2001-05-11 2003-06-25 Rohm And Haas Company Procédé de production d'hydrure de lithium-aluminium à partir d'hydrure de sodium-aluminium
US6676921B2 (en) 2001-05-11 2004-01-13 Rohm And Haas Company Method for preparation of lithium aluminum hydride from sodium aluminum hydride
RU2680491C1 (ru) * 2018-04-20 2019-02-21 Акционерное общество "Государственный Ордена Трудового Красного Знамени научно-исследовательский институт химии и технологии элементоорганических соединений" (АО "ГНИИХТЭОС") Способ получения кристаллического литийалюминийгидрида в среде н-дибутилового эфира

Also Published As

Publication number Publication date
AU4651497A (en) 1998-04-17

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