EP0643682A1 - Procedes et intermediaires pour la preparation de benzaldehydes 2-substitutes - Google Patents

Procedes et intermediaires pour la preparation de benzaldehydes 2-substitutes

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Publication number
EP0643682A1
EP0643682A1 EP93909170A EP93909170A EP0643682A1 EP 0643682 A1 EP0643682 A1 EP 0643682A1 EP 93909170 A EP93909170 A EP 93909170A EP 93909170 A EP93909170 A EP 93909170A EP 0643682 A1 EP0643682 A1 EP 0643682A1
Authority
EP
European Patent Office
Prior art keywords
compound
alkyl
formula
phenyl
process according
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.)
Withdrawn
Application number
EP93909170A
Other languages
German (de)
English (en)
Other versions
EP0643682A4 (fr
Inventor
Kerry Joseph Gombatz
Michael Anthony Smithkline Beecham Pharm. Forth
Jerome Francis Smithkline Beecham Pharm. Hayes
Michael Barry Smithkline Beecham Pharm. Mitchell
Stephen Alexander Smithkline Beecham Pharm Smith
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.)
SmithKline Beecham Ltd
SmithKline Beecham Corp
Original Assignee
SmithKline Beecham Ltd
SmithKline Beecham Corp
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 SmithKline Beecham Ltd, SmithKline Beecham Corp filed Critical SmithKline Beecham Ltd
Publication of EP0643682A1 publication Critical patent/EP0643682A1/fr
Publication of EP0643682A4 publication Critical patent/EP0643682A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/72—Hydrazones
    • C07C251/86—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
    • C07C251/24—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
    • C07C45/516—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of nitrogen-containing compounds to >C = O groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
    • C07C47/546—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings polycyclic

Definitions

  • This invention relates to novel intermediates and processes for preparing useful intermediates in the synthesis of pharmaceutically active agents.
  • 2-Substituted benzaldehydes are useful intermediates for preparing pharmaceuticall active compounds.
  • certain compounds which are leukotriene antagonists an useful in the treatment of asthma may be prepared from 2-substituted benzaldehydes of the general formula (la):
  • R x is (L) a -(CH 2 ) b -(T) c -M; a is 0 or 1; b is 3 to 14; c is 0 or 1;
  • J and T are independently sulfur, oxygen, or C ⁇ and
  • R2 and A are independently selected from H, CF 3 , Ci ⁇ alkyl, C ⁇ _4alkoxy, F, Cl, Br, I, OH, NO2orNH 2; or Ri and A are H and R2 is (L) a -(CH2) b -Cr)c-M wherein a, b, c, L, T, and M are as defined above.
  • Such compounds are disclosed, for instance in U.S. Patent 4,820,719, U.S. Patent
  • Arylcarbimines however, arc reported to have limited synthetic utility due to their tendency to suffer from reaction at the azomethine linkage and alpha- deprotonation. See Org. Reactions, 26, 57-58 (1979). Zeigler et al, J. Org. Chem., 41, 1564 (1976) report that arylcarbimines may be induced to undergo ortho-lithiation if an adjacent ether substituent is present.
  • Patent 4,100,165 reports condensation of a dilithiated 2-(o-tolyl)imidazoline with esters and acyl halides.
  • Current methods for the synthesis of the 2-substituted benzaldehydes of this invention employ expensive reagents or multiple process steps which make them unattractive for commercial preparation of 2-substituted benzaldehydes. There is therefore a need for an efficient alternative method for the preparation of 2-substituted benzaldehydes.
  • Ri is CH 2 CH 2 -(L ⁇ )p-(CH2) q -(L2VCH2-(T) s -Z;
  • R2 and A are independently H, CF3, Ci ⁇ alkyl, F, Cl, Br or I.
  • One feature of this invention is a process for preparing a compound of the formula: (lb) wherein A, Ri, R2, Li, L2, q, p, r, s, T and Z are as defined above for formula (lb), which comprises reacting a compound of the formula:
  • R2 and A are as defined above for formula (lb);
  • R3 is C1.6 alkyl, C3.6 cycloalkyl, (CH 2 )tphenyl or N(R') 2 ;
  • R' is C1.6 alkyl, C3.6 cycloalkyl or (CH 2 ) t phenyl; and tis O or l; with a base and a compound of the formula:
  • Li, L2, p, q, r, s, T and Z are as defined above for formula (lb), and X is a displaceable group; and treating the product thereof with acid.
  • Another feature of this invention is a novel intermediate according to formula (H):
  • R l , R2 and A are as defined for formula (lb);
  • R3 is C1-6 alkyl, C3.6 cycloalkyl, (CH2) t phenyl or N(R')2;
  • R' is Ci-6 alkyl, ' C3-6 cycloalkyl or (CH2) t phenyl; and tis O or l.
  • Another feature of this invention is a process for the preparation of the novel intermediate of formula (H), which comprises reacting a compound of the formula (in):
  • Yet another feature of this invention is an improved process for preparing a compound of the formula (II), which comprises adding a catalytic amount of an organic amine to the reaction mixture prior to addition of the base.
  • Still another feature of this invention is an improved process for preparing a compound of the formula (U), which comprises adding a sodium or potassium alkoxide to the reaction mixture.
  • Another feature of this invention is an improved process for preparing a compound of the formula (II), which comprises conducting the reaction within a specified temperature range.
  • the present invention discloses useful intermediates and a process for the preparation of compounds of formula (lb):
  • Rl is CH 2 CH 2 -(Li)p-(CH2)q-(L2 CH 2 -(T) s -Z;
  • Ci-4alkyl ethynyl, trifluoromethyl, isopropenyl, furanyl, thienyl, cyclohexyl or phenyl optionally mono substituted with CF3, Ci ⁇ alkyl, Ci ⁇ alkoxy, methylthio, or trifiuoromethylthio;
  • R2 and A are independently H, CF3, Ci ⁇ alkyl, F, Cl, Br or I, which comprises reacting a compound of the formula:
  • R2 and A are as defined above;
  • R3 is C1.6 alkyl, C3-6 cycloalkyl, (CH2) t phenyl or N(R')2 ⁇
  • R 1 is C ⁇ _6 alkyl, C3.6 cycloalkyl or (CH2) t phenyl; and t is 0 or 1; with a base and a compound of the formula:
  • Ri is CH 2 CH2-(L ⁇ )p-(CH2)q-(L2) ⁇ -CH2-(T) s -Z;
  • Z is Ci-4alkyl, ethynyl, trifluoromethyl, isopropenyl, furanyl, thienyl, cyclohexyl or phenyl optionally mono substituted with CF3, C ⁇ -4alkyl, Ci ⁇ alkoxy, methylthio, or trifluoromethylthio;
  • R 2 and A are independently H, CF3, Ci-4alkyl, F, Cl, Br or I;
  • R3 is C1-6 alkyl, C3.6 cycloalkyl, (CH 2 )tphenyl or N(R')2 ⁇
  • R' is Ci- alkyl, C3.6 cycloalkyl or (CH 2 ) t phenyl; and
  • t is 0 or 1.
  • Z is phenyl and Li and L 2 are CH 2 CH 2 .
  • R3 is t-butyl.
  • p, r and s are 1.
  • q is 0-2.
  • T is CH2 or C ⁇ C .
  • a preferred compound is N-[2-(8-phenyloctyl)phenyl)-methylene]-l,l- dimethylethanamine.
  • novel intermediates of formula (IT) are prepared by a process which comprises reacting a compound of formula (HI):
  • R2 and A are independently H, CF3, C ⁇ -4alkyl, F, Cl, Br or I;
  • R3 is C 1 -6 alkyl, C3.6 cycloalkyl, (CH 2 ) t phenyl or N(R') 2 ;
  • R' is Ci- t j alkyl, C3.6 cycloalkyl or (CH2)rPnenyl; and tis O or l; with a base and a compound of the formula (IV):
  • this invention discloses a process for preparing a compound of formula (lb) which comprises reacting a compound of formula (HI) with a base and a compound of formula (TV) and treating the reaction mixture with acid.
  • the overall conversion is accomplished in a single reaction vessel without isolation of the intermediate product. This process utilizes readily available materials and proceeds in efficient yield in a minimum number of process steps.
  • Tfl Compounds of formula (Tfl) are hydrazones and imines, or Schiff bases, and are generally prepared by any means common to the art for preparing such compounds.
  • One method for preparing the imines comprises reacting a compound of formula (V):
  • (V) with an amine or a hydrazine of the formula, R3-NH 2 Such reactions are normally conducted by admixing the reactants in a non-aqueous solvent and optionally heating the two reactants.
  • Dehydrating agents may be used to drive the reaction towards product if necessary. Common dehydrating agents are, for instance, molecular sieves or magnesium sulfate. Alternatively, dehydration may be effected by azeotroping the water produced by the reaction from an appropriate solvent, such as benzene or toluene.
  • the group R3 is C ⁇ ⁇ alkyl, C3 ⁇ cycloalkyl, benzyl, phenyl or N ' .
  • the electrophile given by formula (TV), is prepared by conventional methods, such as those disclosed in U.S. Patent 4,820,719, U.S. Patent 4,874,792, EPA 0296732 and Perchonock et al., J. Med. Chem., 28, 1145 (1985) which are incorporated herein by reference.
  • the X moiety of the electrophile represents a displaceable group, which may be any group capable of being displaced by the carbon nucleophile prepared from the compound of formula ( ⁇ I).
  • a large number of displaceable groups are suitable, such as alkyl and aryl sulfonates, alkyl and aralkyl acetates, benzoates and halogens.
  • Representative of the class are Cl, Br, I, R 4 SO3 and R4CO wherein R4 is Ci ⁇ alkyl, optionally substituted by 1-5 fluorine atoms, or phenyl, optionally substituted by one or two halogen, Ci ⁇ alkyl, C ⁇ _4alkoxy or nitro groups.
  • Representative displaceable groups arc toluenesulfonate, bromobenzenesulfonate, nitrobenzene-sulfonate, methanesulfonate, trifluoromethanesulfonate, acetate, chloroacetate, trifluoroacetate, benzoate, bromobenzoate, chlorobenzoate, nitrobenzoate, chloro, bromo and iodo. Chloro and bromo are preferred. Chloro is especially preferred.
  • the X group of the compounds of formula (IN), if not present in the precursor, is prepared from the corresponding alcohol by reaction with an appropriate acyl halide, anhydride, sulfonyl halide or appropriate halogenating agent.
  • Typical of such reagents are toluenesulfonyl chloride, bromobenzenesulfonyl chloride, nitrobenzenesulfonyl chloride, methanesulfonyl chloride, acetyl chloride, chloroacetyl chloride, trifluoroacetic anhydride, benzoyl chloride, bromobenzoyl chloride, ch-orobenzoyl chloride, nitrobenzoyl chloride, oxallyl chloride or bromide, hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphorous tribromide, phosphorous trichloride, phosphorous oxychloride and carbon tetrabromide with triphenyl phosphine.
  • T is CH2, Li or L2 are CH2CH2, and Z is Ci-4alkyl or phenyl are generally available commercially.
  • Compounds wherein T is O, S or C ⁇ C may be prepared by reacting the compound H-T-Z with a compound of the structure X-CH2-(Li) p -(CH 2 )q-(L2)rCH2-X, wherein X, Li, L 2 , T, p, q and r are as defined above, in the presence of an appropriate base.
  • a palladium catalyst such as 5% palladium on carbon
  • l-bromo-7-phenylheptane is prepared from 1,5-dibromopentane and phenylacetylene in the presence of n-butyl lithium, followed by reduction with hydrogen over a palladium catalyst.
  • 1-bromo or l-chloro-7- phenylheptane may be prepared via a copper mediated coupling of benzyl magnesium halide with 1,6 dibromohexane or l-bromo-6-chlorohexane.
  • Alkylation of the carbimine of formula (HI) is initiated by reacting a compound of formula (HI) with a strong base to deprotonate the ortho methyl group. Since the metallated intermediate is reactive with water, the activation reaction is suitably carried out in an inert, dry atmosphere, such as nitrogen or argon, although dry air is sufficient.
  • the activation reaction is carried out in an aprotic solvent.
  • Suitable solvents for this reaction arc common aliphatic or aromatic hydrocarbon solvents which are unreactive to strong bases. Representative of such solvents are diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane, toluene, benzene, pentane, hexane and petroleum ethers, and mixtures thereof. Diethyl ether, dioxane and tetrahydrofuran are preferred. Tetrahydrofuran is especially preferred.
  • a base of sufficient strength to deprotonate the ortho methyl group is required. Any base capable of effecting such deprotonation without causing appreciable side reactions is suitable.
  • Typical of such bases are an alkali metal alkyl, an alkali metal amine (e.g., a salt of an organic or inorganic amine), or an alkali metal aryl.
  • alkali metal alkyl an alkali metal amine (e.g., a salt of an organic or inorganic amine), or an alkali metal aryl.
  • Representative of such bases are n-butyl lithium, sec-butyl lithium, methyl lithium, phenyl lithium, lithium diisopropylamide, lithium tetramethylpiperidide, lithium diethylamide or lithium amide, or the corresponding sodium or potassium salt of any of these species.
  • Alkyl lithium reagents are especially suitable.
  • n-Butyl lithium, lithium tetramethylpiperidide and lithium diisopropylamide are preferred.
  • the metal of the base initially used may be exchanged for another metal, for instance another alkali metal, copper, magnesium or zinc. It is often helpful to use a slight molar excess of base, such as 1% to 25%, to ensure complete metallation. About one molar equivalent is normally satisfactory. It will be apparent to one skilled in the art that certain of these bases, such as alkali metal alkyl or aryl, may be incompatible with a halogen substituent in the carbimine, and that other bases, such as lithium diisopropylamide would be more suitable.
  • the reaction of a compound of formula (HI) with the base is carried out by admixing the two reactants.
  • the reaction should be carried out at a temperature sufficient to cause the base to deprotonate the ortho methyl group, yet not so high as to cause adverse side reactions.
  • the optimum temperature will be dependent upon the base used and the imine reactant If the base is a lithium dialkyl amide, typically the reaction is carried out between about -20°C and 60°C; suitably, the reaction is carried out between about -10°C and40°C.
  • reaction solution is diluted with an appropriate solvent, washed with water and concentrated in vacuo to an oil. If a purified product is desired, the product is purified by distillation, or, if appropriate, by crystallization.
  • mineral acids, organic acids and the like are considered to be sufficiently strong acids.
  • methanesulfonic acid, toluenesulfonic acid, trifluoroacetic acid, benzoic acid, acetic acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid and phosphoric acid are all suitable.
  • Mineral acids are preferred.
  • Hydrochloric acid is especially preferred.
  • the reaction mixture containing the product (H) is hydrolyzed directly by the addition of acid to the reaction mixture.
  • the reaction mixture is added to a cooled solution of the acid and thereafter allowed to warm to room temperature.
  • the reaction mixture may be monitored for formation of the desired benzaldehyde, such as by analytical chromatography, but typically the reaction is stirred from about 1 h to about 24 h.
  • the product is then isolated by conventional techniques, such as extractive w ⁇ rkup.
  • An improved process for preparing a compound of the formula (IT) comprises adding a catalytic amount of an organic amine to the reaction mixture prior to addition of the base, particularly when an alkyl lithium reagent is used as the base.
  • the organic amine is a secondary amine.
  • Representative amines are diethylamine, diisopropylamine, dicyclohexylamine, piperidine, 2,6-dimethylpiperidine, and 2,2,6,6-tetramethylpiperidine. Diisopropylamine, dicyclohexylamine, and 2,2,6,6-tetramethylpiperidine are especially suitable.
  • the catalytic amount may be from about 0.01 to about 0.3 molar equivalents of organic amine relative to the carbimine. About 0.01 to about 0.15 molar equivalents is suitable. About 0.01 to 0.1 molar equivalents is typical, depending on the amine used. For instance, about 0.01 to about 0.05 equivalents are useful for diisopropylamine and 2,2,6,6-tetramethylpiperidine.
  • Still another feature of this invention is an improved process for preparing a compound of the formula (H), which comprises preparing a sodium or potassium salt of the carbimine of formula (HI) and reacting the product with a compound of the formula (IV).
  • the 2-methyl-phenyl carbimine of formula (IH) may be treated with a base such as n-butyllithium or lithium diisopropylamide, to form the lithium salt, and further treated with a sodium or potassium base or salt to form the desired salt by a metal exchange reaction.
  • Sodium or potassium alkoxide, or sodium or potassium trifluoroacetate are representative bases/salts.
  • reaction was stirred for 15 min with cooling then l-bromo-7-phenylheptane (72.9 g, 0.286 mol) in tetrahydrofuran (75 mL) was quickly added.
  • the reaction mixture was stirrcd for 1 h with cooling then allowed to warm to room temperature and stirred for an additional 14 h.
  • the reaction mixture was assayed by gas chromatography for product imine (RT 19.8 min., DB-1 , 30 m X 0.53 mm, program, 100°C for 5 min, 100-260°C at 15°C min, hold at 260°C for 12 min.).
  • the product was isolated by dilution of the reaction mixture with water and methylene chloride, quickly washing the organic mixture with water, and concentrating the solution to an oil. The oil was purified by distillation.
  • reaction was stirred for 15 min with cooling then l-bromo-7-phenylheptane (72.9 g, 0.286 mol) in tetrahydrofuran (75 mL) was quickly added.
  • the reaction mixture was stirred for 1 h with cooling then allowed to warm to room temperature and stirred for an additional 14 h.
  • the reaction mixture was quenched with aqueous 10% hydrochloric acid solution, and was stirred for 1 h at 0°C then at ambient temperature for 14 h.
  • the reaction mixture was poured into methylene chloride (700 mL) and stirred for 5 min. The organic layer was removed, and the aqueous layer extracted with methylene chloride (2 x 700 mL).
  • N-[(2-methylphenyl)methylene]-l,l-dimethylethanamine (5.00 g, 29 mmol) was added to a solution of lithium diisopropylamide [28.5 mmol; prepared from diisopropylamine (4.0 mL, 2.89 g, 29 mmol) and n-butyl lithium (2.5 M, 11.43 mL, 28.5 mmol)] in THF (50 mL) at -10°C. After stirring at this temperature for 75 min, a solution of potassium t-butoxide (1.49 M, 19.2 mL, 28.5 mmol) in THF was added.
  • a) phenylheptylbromide/phenylheptyliodide i.) To a solution of N-[(2-memylphenyl)methylene]-l,l-din ⁇ ethylethanamine (5.0 g, 0.03 mol) and N.NJSf'.N'-tetramethylethylene diamine (3.31 g, 0.03 mol) in tetrahydrofuran (40 mL), n-butyl lithium (2.5 M, 11.4 mL, 0.03 mol) at 0°C was slowly added.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention se rapporte à des procédés pour préparer des benzaldéhydes 2-substitués, représentés par la formule générale (I), où: R1 représente CH2CH2-(L1)p-(CH2)q-(L2)r-CH2-(T)s-Z; L1 et L2 représentent séparément CH2CH2, CH=CH ou C=C; q est compris entre 0 et 8; p, r et s représentent séparément 0 ou 1; T représente O, S, CH2, CH=CH, C=C; et Z représente alkyle C1-4, éthynyle, trifluorométhyle, isopropényle, furanyle, thiényle, cyclohexyle ou phényle éventuellement monosubstitué par CF3, alkyle C1-4, alcoxy C1-4, méthylthio ou trifluorométhylthio; et R2 et A représentent séparément H, CF3, alkyle C1-4, F, Cl, Br ou I; ces benzaldéhydes servant à préparer des composés pharmaceutiquement actifs.
EP93909170A 1992-03-25 1993-03-25 Procedes et intermediaires pour la preparation de benzaldehydes 2-substitutes. Withdrawn EP0643682A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US85838492A 1992-03-25 1992-03-25
US858384 1992-03-25
PCT/US1993/002803 WO1993019033A1 (fr) 1992-03-25 1993-03-25 Procedes et intermediaires pour la preparation de benzaldehydes 2-substitutes

Publications (2)

Publication Number Publication Date
EP0643682A1 true EP0643682A1 (fr) 1995-03-22
EP0643682A4 EP0643682A4 (fr) 1995-06-07

Family

ID=25328179

Family Applications (1)

Application Number Title Priority Date Filing Date
EP93909170A Withdrawn EP0643682A4 (fr) 1992-03-25 1993-03-25 Procedes et intermediaires pour la preparation de benzaldehydes 2-substitutes.

Country Status (16)

Country Link
EP (1) EP0643682A4 (fr)
JP (1) JPH07507060A (fr)
KR (1) KR950701310A (fr)
CN (1) CN1078229A (fr)
AU (1) AU3967993A (fr)
CA (1) CA2132639A1 (fr)
FI (1) FI944413A (fr)
HU (1) HUT70046A (fr)
IL (1) IL105128A0 (fr)
MA (1) MA22843A1 (fr)
MX (1) MX9301626A (fr)
NO (1) NO943548L (fr)
SI (1) SI9300146A (fr)
TW (1) TW267157B (fr)
WO (1) WO1993019033A1 (fr)
ZA (1) ZA932049B (fr)

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TWM317981U (en) 2007-02-16 2007-09-01 Int Bicycle Products Corp Handlebar of transportation vehicle
CN108689861B (zh) * 2018-05-28 2021-02-26 吉林大学 一种n-乙基-3-苯基丙胺的制备方法
CN113620761B (zh) * 2021-08-26 2022-06-17 西北工业大学 苯硅烷还原芳基仲酰胺或芳基仲酰胺衍生物合成芳基醛类化合物的制备方法

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US3637851A (en) * 1967-10-18 1972-01-25 Tenneco Chem N - cycloalkyl-chlorobenzylidenimines and herbicidal compositions containing same
US3466164A (en) * 1968-03-29 1969-09-09 Tenneco Chem Process for the control of plant growth with n-(substituted benzylidene) alkyl amines
US3910944A (en) * 1974-11-20 1975-10-07 Upjohn Co Spiro(cyclopropane-1,4{40 -(4H)-s-triazolo-(4,3-a)(1,4)benzodiazepines)
US4198349A (en) * 1977-10-06 1980-04-15 William H. Rorer, Inc. Benzylideneaniline derivatives
US4231962A (en) * 1978-06-08 1980-11-04 Ciba-Geigy Corporation 3-Phenoxybenzylideneamines and 3-benzylbenzylideneamines
US4874792A (en) * 1985-04-19 1989-10-17 Smithkline Beckman Corporation Thiophenyl Alkanoic acids useful as leukotriene antagonists
DE3535451A1 (de) * 1985-10-04 1987-04-09 Bayer Ag Verfahren zur herstellung von n-alkyl-substituierten hydroxylammoniumchloriden und neue n-alkyl-substituierte hydroxylammoniumchloride

Non-Patent Citations (2)

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Title
No further relevant documents disclosed *
See also references of WO9319033A1 *

Also Published As

Publication number Publication date
KR950701310A (ko) 1995-03-23
ZA932049B (en) 1994-09-21
SI9300146A (sl) 1993-12-31
JPH07507060A (ja) 1995-08-03
WO1993019033A1 (fr) 1993-09-30
CA2132639A1 (fr) 1993-09-30
IL105128A0 (en) 1994-01-25
NO943548D0 (no) 1994-09-23
NO943548L (no) 1994-11-23
EP0643682A4 (fr) 1995-06-07
MA22843A1 (fr) 1993-10-01
HU9402743D0 (en) 1994-12-28
MX9301626A (es) 1994-07-29
FI944413A0 (fi) 1994-09-23
TW267157B (fr) 1996-01-01
FI944413A (fi) 1994-11-23
HUT70046A (en) 1995-09-28
AU3967993A (en) 1993-10-21
CN1078229A (zh) 1993-11-10

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