Showing papers on "Grignard reaction published in 1993"

Synthesis and structure-property relationships of regioirregular poly(3-hexylthiophenes)

Abstract: The regioselectivity of coupling reactions has been investigated in order to determine the origin of regioregularity in poly(3-alkylthiophenes) prepared by the Grignard method. Reaction of equimolar quantities of 2,5-diiodo-3-hexylthiophene and Mg results in the formation of Grignards primarily at the 5-position, while di-Grignard accounts for ∼60% of reacted magnesium. Condensation of di-Grignards with 2-iodo-3-hexylthiophene, the most sterically crowded coupling reaction, shows only modest regioselectivity in favor of head-to-tail configurational isomers. Polymerization of reaction mixtures containing large fractions of di-Grigard resulted in polymers with low degrees of regioregularity

The Barbier reaction and related one-step processes

Abstract: 1 Introduction.- 1.1 Magnesium: A New Metal in Organic Synthesis.- 1.2 The Early History of Organozinc Chemistry.- 1.2.1 The Beginning of Organozinc Chemistry.- 1.2.2 Improvement of the Preparation of Diethylzinc.- 1.2.3 Synthetic Applications of Organozinc Compounds.- 1.2.4 Barbier Reaction: Saytzeff or Frankland Reaction?.- 1.2.5 Zinc in Organic Chemistry.- 1.3 The Early History of Organomagnesium Chemistry.- 1.3.1 Pre-Barbier Period.- 1.3.2 Magnesium in Synthetic, Organic Chemistry.- 1.4 The Barbier Reaction.- 1.5 More Recent Developments in Barbier Chemistry.- 1.6 Contents of the Following Chapters.- 1.7 References.- 2 Synthetic Applications of the Barbier Reaction.- 2.1 Synthetic Procedures: One-Step or Two-Step?.- 2.2 The Replacement of Zinc by Magnesium in the Reformatsky Reaction.- 2.3 Barbier Reactions with Allylic Halides.- 2.3.1 Introduction.- 2.3.2 The Jaworsky Reaction.- 2.3.3 Allylmagnesium Halides.- 2.3.4 More Barbier-Type Reactions with Allylic Halides.- 2.3.5 Allylic Rearrangements.- 2.4 Other Barbier Reactions.- 2.4.1 Introduction.- 2.4.2 Intramolecular Barbier Reactions.- 2.4.3 Reactions with Cyclic Acetals.- 2.4.4 Miscellaneous Barbier Reactions.- 2.4.5 Barbier Reactions with Halides of Various Elements.- 2.5 Conclusion.- 2.6 References.- 3 Barbier-Type Reactions with Other Metals.- 3.1 Introduction.- 3.2 Sodium in One-Step Processes.- 3.3 Lithium in Barbier-Type Reactions.- 3.3.1 Cyclization Reaction 1968.- 3.3.2 One-Step Alternative to the Grignard Reaction.- 3.3.3 Allylic Mesitoates.- 3.3.4 Cyclization Reactions 1975.- 3.3.5 Reactions with Nitriles and Nitrosoalkanes.- 3.3.6 Reactions with Sterically Crowded Halides 1978.- 3.3.7 Ultrasound in Li-Barbier Reactions.- 3.3.8 Other Li-Barbier Reactions with Sterically Hindered Reagents 1988.- 3.3.9 Li-Barbier Reactions with n-Butyllithium.- 3.4 Zinc in Barbier-Type Reactions.- 3.4.1 Introduction.- 3.4.2 'Saytzeff Reactions' with Propargylic Halides.- 3.4.3 Zn-Barbier Reactions with Perfluoro Haloakanes.- 3.4.4 Other Zn-Barbier Reactions Solvents, Activating Agents.- 3.4.5 Conclusion.- 3.5 Other Metals in Barbier-Type Reactions.- 3.6 Summary.- 3.7 References.- 4 The Mechanism of the Barbier Reaction.- 4.1 Introduction.- 4.2 Mechanism of the Interaction of Metals with Organo Halides.- 4.2.1 Early Work by Polanyi et al. 1934.- 4.2.2 'High Temperature Species' 1967.- 4.2.3 Vapourization of Metals and Codeposition with Reactants.- 4.2.4 Conclusion.- 4.3 Mechanism of the Grignard Reagent Formation Reaction.- 4.3.1 Introduction.- 4.3.2 Studies on Radical Formation.- 4.4 Mechanism of the Barbier Reaction.- 4.4.1 Introduction.- 4.4.2 Radical Formation.- 4.4.3 Conclusion.- 4.5 References.- 5 Experimental Procedures for Barbier Reactions.- 5.1 Introduction.- 5.2 Starting Heterogeneous Reactions with Metals.- 5.2.1 Introduction.- 5.2.2 Anhydrous Reaction Conditions.- 5.3 Reactions with Magnesium.- 5.3.1 Introduction.- 5.3.2 Surface of Metallic Magnesium.- 5.3.3 New Developments in Activation of Magnesium.- 5.3.4 General Conclusion Regarding Magnesium Activation.- 5.4 Reactions with Lithium.- 5.4.1 Introduction.- 5.4.2 Activation of Lithium Metal.- 5.5 Reactions with Zinc.- 5.5.1 Introduction.- 5.5.2 Chemical Activation of Zinc.- 5.5.3 Other Techniques to Activate Zinc.- 5.5.4 General Conclusion Regarding Zinc Activation.- 5.6 References.

Optically Active Antifungal Azoles. I. Synthesis and Antifungal Activity of (2R, 3R)-2-(2, 4-Difluorophenyl)-3-mercapto-1-(1H-1, 2, 4-triazol-1-yl)-2-butanol and Its Stereoisomers

Abstract: (2R,3R)-2-(2,4-Difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl )-2-butano l [(2R,3R)-7] and its stereoisomers [(2S,3R)-, (2S,3S)- and (2R,3S)-7] were prepared from the optically active oxiranes 6 by a newly developed ring-opening reaction and evaluated for antifungal activity. The thiol (2R,3R)-7 showed extremely potent antifungal activity in vitro and in vivo. The optically active oxirane (2R,3S)-6, a useful intermediate for the synthesis of sulfur-containing antifungal azoles 5, was synthesized from methyl (R)-lactate [(R)-8] via eight steps in a stereocontrolled manner. The key step in the synthesis is the Grignard reaction of an amide derivative [(R)-12a] of (R)-lactic acid with 2,4-difluorophenyl-magnesium bromide (13).

Organomercury Compounds. XXXI. Preparations and 199Hg N.M.R. Spectra of Organomercury Derivatives of 2-Phenylpyridine, Benzo[h]quinoline, 1-Phenylpyrazole and 3,4,5-Trimethyl-1-phenylpyrazole, and the X-Ray Crystal Structure of Bis[2-(pyridin-2'-yl)phenyl]mercury

Abstract: 2-(Pyridin-2'-yl) phenylmercuric acetate has been prepared by mercuration of 2-phenylpyridine. Symmetrization of the corresponding chloride by alkaline sodium stannite gave bis [2-(pyridin-2'-yl)phenyl]mercury, which was also prepared from 2-(2'-aminophenyl)pyridine by the diazo method and treatment of the initial product with copper powder and aqueous ammonia. Mercuration of benzo [h] quinoline and 3,4,5-trimethyl-1-phenylpyrazole with mercuric acetate followed by treatment with lithium chloride yielded benzo [h]quinolin-10-ylmercuric chloride and 2-(3',4',5'-trimethylpyrazol-1'-yl) phenylmercuric chloride respectively. Treatment of the former product with tribromide ions gave 10-bromobenzo[h] quinoline. The exchange Grignard reaction between 1-phenylpyrazole and ethylmagnesium bromide to give 2-(pyrazol-1'-yl) phenylmagnesium bromide has been monitored by reactions with benzonitrile and D2O to establish optimum conditions for reaction with mercuric bromide giving bis [2-(pyrazol-1'-yl)phenyl]mercury. The 199Hg n.m.r. chemical shifts of the majority of mercurials are shifted substantially downfield relative to the corresponding simple phenylmercurials consistent with weak intramolecular coordination by the heterocyclic nitrogen donor atoms, but a small upfield shift is observed for bis [2-(pyrazol-1'-yl)phenyl]mercury. The X-ray crystal structure of bis [2-(pyridin-2′-yl)phenyl]mercury [monoclinic, space group P21/n, a 12.746(2), b 11.660(2), c 5.698(1) Ǻ, β 92.81(1)′, V 845.8 Ǻ3] shows a centrosymmetric molecule with strong linear two coordination [Hg-C 2.098(8) Ǻ; C-Hg-C 180.0°] and significant but much weaker Hg-N interactions [Hg-N 2.798(7) Ǻ; N-Hg-N 180.0°] giving overall distorted square planar stereochemistry. The phenyl rings are mutually coplanar, whilst the two pyridin-2'-yl rings are parallel and inclined at 10.8° to the phenyl groups.

Preparation of enantiomerically pure phosphine oxides by nucleophilic displacement chemistry using oxazaphospholidines

Abstract: The synthesis of enantiomerically pure triaryl- and diarylvinyl-phosphine oxides from PCl3 by three sequential nucleophilic displacements at phosphorus is demonstrated. A single diastereoisomer of the P-chlorooxazaphospholidine 4 is treated with an arylmagnesium halide to effect displacement of chloride. The major stereoisomer is formed with retention of configuration. After oxidation to the phosphine oxide with tert-butyl hydroperoxide, a second Grignard reaction leads to regiospecific and stereospecific P–O ring cleavage so that a second aryl group is introduced with retention of configuration. For the final step, the P–N bond is subjected to acid-catalysed methanolysis, previously shown to occur with inversion of configuration, followed by P–OMe displacement with a third arylmagnesium halide. The overall yield of triarylphosphine oxide is up to 29% for the cited five steps. Simple methoxyaryl or 2-naphthyl residues are employed to demonstrate the methodology, which permits the multigram-scale preparation of this class of compound in 94% e.e. The stereochemical course of the nucleophilic displacements with arylmagnesium halides is consistent with a model in which the organomagnesium reagent is complexed to the oxo-group and attacks phosphorus cis-to it in a direction defined by both electronic and steric factors.

Chiral synthons from carvone. 9. Radical annulation strategy to chiral pupukeanones: total synthesis of (+)-10-exo-(1-naphthyl)pupukean-9-one and (+)-10-exo-(1-naphthyl)-5-epipupukean-9-ones

Abstract: Intramolecular alkylation reaction of the bromoenone 12, obtained from S-carvone in three steps furnished the bicycle[222] octenone 13 Contrary to the anticipated radical annulation reaction, the bicyclic bromides 14 and 15, obtained from the enone 13, generated exclusively the cyclopropane product 18 via a 3-exo trig radical cyclization on reaction with nBu3SnH and AIBN, even in the presence of a large excess of a radicophile On the other hand, bromoenone 24, synthesized from R-carvone via S-naphthylcarvone 21, underwent radical annulation reaction in the presence of radicophiles to furnish the isotwistanes 25-28 in a regio- and stereospecific manner Hydrogenation of the olefin 34, obtained from the diketone 27 via a regiospecific Wittig reaction, furnished the naphthyl-5-epipupukean-9-one 33, whereas stereoselective hydrogenation of the enone 36, prepared from the keto ester 25 via a Grignard reaction and dehydration sequence, generated the naphthylpupukeanone 32

Process for the purification of 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol and its salts

Abstract: A process for the improved purification and separation of trans 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol hydrochloride from a reaction mixture containing the trans isomer, the cis isomer and Grignard reaction side products, comprising combining the mixture with a solution of hydrochloric acid in a low molecular weight alcohol or with gaseous hydrogen chloride in the presence of an organic solvent selected from medium molecular weight alcohols, ketones, esters and ethers or aromatic ethers, to effect the selective precipitation of trans 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol hydrochloride.

Synthesis and reactions of some 3-cyano-4-methylcoumarins

Abstract: o-Hydroxy ketones (I) were converted into 3-cyano-4-methylcoumarins (II) via condensation with ethyl cyanoacetate in presence of piperidine or ammonium acetate as a catalyst. The behavior of compound (II) towards Grignard and Michael reactions was investigated. The reactions of 3-acetylcoumarin (III) with hydrazines under different conditions were carried out to give the hydrazone (IV a), phenylhydrazone (IV b) and pyrazole (V) derivatives. Also, the 4-styryl derivatives (VI) were obtained by condensation of II with different aromatic and heterocyclic aldehydes. A one pot synthesis of Michael product (VII) from the reaction of VI with malononitrile was described

Total Synthesis of (±)-Meridinol, (±)-Epimeridinol, and a Related Cyclolignan

Abstract: The naturally occurring lignan meridinol [5] was synthesized in a racemic form in a convergent manner involving a Grignard reaction on E-4-(3,4-methylenedioxybenzylidene)-2,3(2H,5H)-furandione [7]. The hitherto unknown epimeridinol [11] and the cyclolignan 15 were also prepared. The structure assignments of the synthesized lignans are determined by their spectroscopic data

The Synthesis of Poly[N-(p-vinylbenzylidene)-t-butylamine N-oxide] and Characterizations of Reaction with Nitrogen Dioxide

Abstract: Polymer-supported spin trap, poly[N-(p-vinylbenzylidene)-t-butylamine N-oxide] (polyPBN), was prepared by using p-chlorostyrene as a starting material, followed by Grignard reaction, condensation with t-butylamine, reduction, polymerization, and oxidation. The adsorption ability of NO2 by polyPBN was investigated in a closed-circulation system. PolyPBN maintains its original NO2 adsorbing ability in the mixed gas of nitrogen and nitrogen dioxide saturated with water vapor even after repeated (5 times) use. However, when the gaseous phase is freed from water, polyPBN exhibits less efficiency to adsorb NO2 and its adsorbing ability decreases gradually with the repeated use.

Synthesis of 2,5-dibromobenzaldehyde and its reaction with hexylmagnesium bromide

Abstract: 2,5-Dibromobenzaldehyde (3) is synthesized by the oxidation of 2,5-dibromotoluene (1) via 2,5-dibromobenzylidene diacetate (2). Grignard reaction of hexylmagnesium bromide with 2 gives the normal addition product, 2,5-dibromo-α-hexylbenzyl alcohol (5) and reduced product, 2,5-dibromobenzyl alcohol (6)

Siloxane compound containing vinyl group and its production

Abstract: PURPOSE:To provide a new compound having quick curability and useful as a stopper for a base oil of e.g. addition reaction-type silicone resin and UV- curable silicone resin, a synthetic intermediate, etc. CONSTITUTION:The compound of formula I [R is vinyl; R is (substituted) 1-10C univalent hydrocarbon group excluding aliphatic unsaturated bond; n is 0-100], e.g. the compound of formula II. The compound of formula I can be produced by carrying out Grignard reaction of a compound of formula III (X is halogen or alkoxy) with a compound of formula IV (R is vinyl; X is halogen) and distilling the reaction product.

Syntheses of 1-substituted 12-oxahexacyclo[7.2.1.02,8.03,7.04,11.06,10]dodecanes and their transformation into pentacyclo[6.3.0.02,6.03,10.05,9]undecane derivatives

Abstract: The reaction of nucleophilic reagents (organomagnesium and organosodium compounds containing active methylene groups) with exo-II-bromopentacyclo[5.4.0.0 2,6 .0 3,10 .0 5,9 ]undecan-8-one leads to the formation of 1-substituted-12-oxahexacyclo[7.2.1.0 2,8 .0 3,7 .0 4,11 .0 6,10 ]dodecanea in the synthesis of trishomocubane derivatives. It is shown, using the 1-methyl- and 1-phenyl-substituted 12-oxadodecanes, that iodotrimethylsilane readly cleaves the ether bond at C(1). The resulting carbonium ions rearrange to form 1,7,11-trisubstituted pentacyclo[5.4.0.0 2,6 .0 3,10 .0 5,9 ]undecane

Synthesis of [20,21-13C2]-pregnenolone

Abstract: The synthesis of [20,21-13C2]-pregnenolone (7) from androst-5-en-3β-ol-17-one (1) is described. Labelled carbons were introduced by two procedures, namely, condensation of 1 with K13CN and Grignard reaction of nitrile derivative 5 with [13C]-methylmagnesium iodide. Location of labels was confirmed by 13C-NMR spectroscopy.

Diastereoselective Conjugate Addition for Construction of Taxane Precursors

Abstract: Copper catalyzed conjugate addition of Grignard reagents to enones was effected with high 1,4-diastereoinduction and was used for the preparation of taxane precursors.

Facile Synthesis and Reactions of (Z)-α,β-Didehydroamino Aldehydes from (Z)-α,β-Didehydroamino Acid Esters

Abstract: The general synthesis of (Z)-α,β-didehydroamino aldehydes 3 was accomplished by the reduction of (Z)-α, β-didehydroamino acid esters with lithium aluminum hydride followed by Swern oxidation. Subsequent Grignard reaction of 3 with alkylmagnesium halides was carried out to give various N-protected amino alkenols and amino alkadienols

Dihydrobenzene-1,4-derivative

Abstract: PURPOSE:To provide a dihydrobenzene-1,4-derivative exhibiting a wide liquid crystal temperature range, having a low activity, and giving a low viscous liquid crystal composition within a wide temperature range, when mixed with other liquid crystal compositions CONSTITUTION:A compound of formula I (A is 1,4-dihydrophenylene; R is H, alkyl, trans-4-alkylcyclohexyl; R' is H, halogen, CF3, OCF3, CN, alkyl, alkoxy; X, Y are H, halogen), eg 1-pentyl-4-(4-fluorophenyl) dihydrobenzene The compound is produced by reacting a p-substituted cyclohexane of formula II with a Grignard reagent of formula III under the usual condition of the Grignard reaction and subsequently dehydrating the produced 1-hydroxy-4-substituted cyclohexene derivative of formula IV The compound has large mutual compatibility with a wide range of liquid crystal substances, is employed together with other liquid crystal substances as constituting substances for a liquid crystal composition, and is extremely useful for improving the liquid crystal composition

Preparation of biphenyl derivatives

Abstract: PURPOSE: To obtain by a new process the subject compound useful as an intermediate of a medicament for cardiovascular disease or angiotensin II receptor antagonist by reacting a specific boronic acid derivative with a substituted phenylhalogen compound. CONSTITUTION: The target compound of formula III is obtained by reacting a compound of formula I (X is optionally protected formyl), e.g. 4- formylbenzeneboronic acid, with a substituted phenylhalogen compound of formula II (Hal is a halogen; R is an inert group to the reaction conditions of the synthesis), preferably 4-bromobenzaldehyde diethylacetal or the like, preferably using a palladium catalyst. The reaction is carried out preferably in a mixed solvent of toluene and ethanol as a reaction solvent at 20 to 150°C and under the pressure of 1 to 5 bar. The compound of formula I may be obtained by the Grignard reaction started from a folmylbenzene halide. COPYRIGHT: (C)1994,JPO

Synthesis of 2,5‐Dibromobenzaldehyde and Its Reaction with Hexylmagnesium Bromide.

Abstract: 2,5-Dibromobenzaldehyde (3) is synthesized by the oxidation of 2,5-dibromotoluene (1) via 2,5-dibromobenzylidene diacetate (2). Grignard reaction of hexylmagnesium bromide with 2 gives the normal addition product, 2,5-dibromo-α-hexylbenzyl alcohol (5) and reduced product, 2,5-dibromobenzyl alcohol (6)

Natural Products. Antitubulin Effect of Congeners of N-Acetylcolchinyl Methyl Ether: Synthesis of Optically Active 5- Acetamidodeaminocolchinyl Methyl Ether and of Demethoxy Analogues of Deaminocolchinyl Methyl Ether.

Abstract: Trimethoxy-substituted dihydrodibenzocycloheptenes 4–7, required for a structure–activity study measuring the inhibition of tubulin polymerization in vitro, were synthesized by four different routes: (1) Synthesis of 4 was achieved from 2,3-dimethoxybenzaldehyde via biphenyl aldehyde 17, chain lengthening to propionic acid 20, acid-catalyzed cyclization toward ketone 21, and removal of the carbonyl group. (2) Compound 5 was obtained by eliminating the sterically most hindered methoxy group in 25 or 26 by metal reduction in alcohol. (3) Compound 6 was prepared from biphenyl aldehyde 34 obtained by Grignard reaction on oxazoline 32. (4) Compound 7 was obtained by reductive deoxygenation of the tetrazolyl ether derivative of N-acetylcolchinol 41. The key role of the aromatic oxygen atoms in colchicine and allo congeners as points of interaction with the colchicine binding site on tubulin was demonstrated by the lack of inhibitory activity of compounds 4–7. Optically active 5-acetamide 8a,b isomers of N-acety...

Isolation of tramadol from Grignard reaction mixt. - by selective pptn. of hydrochloride salt

Abstract: Isolation of trans-2-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexanol hydrochloride of formula (I) from a reaction mixt. contg. the trans and cis isomers (of the free base) and Grignard reaction by-products, is effected by treating the mixt. with a soln. of HCl in a lower alcohol, or with HCl gas in the presence of an organic solvent (II), whereby (I) is selectively pptd. (II) is selected from alcohols of medium molecular wt., ketones, esters, ethers and aromatic ethers. USE/ADVANTAGE - Trans-2-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexanol (tramadol) is a non-addictive analgesic (US3652589 and GB992399). The process is simpler than the prior art processes and avoids using hazardous dioxan. (I) with a purity of 86-99% may be obtained in yields of 38-66%.

Synthetic method of 11,19-cyclopolymerized pregnenone analogue

Abstract: This invention is a synthesis of substituted pregnenone analogue. In its structural formula, R,R1, R2, and R3 are respectively substituted groups of H, OH, N(CH3)2, OCH3, COCH3, R4-C(O)-O- alkyl, alkenyl, alkynyl, etc.. The preparation of above-mention product may be made from various initial raw material mainly through Witting reaction, Grignard reaction, Birch reaction, hydrolysis, etc.. A preliminary pharmacological test verifies that it has the effect of contraceptive hormone, and has obvious anti-conceptive effect for mouse.

Experimental Procedures for Barbier Reactions

Abstract: In general, not only experimental skill and experience are required to carry out a planned organic synthesis. Some precautions have to be taken and some conditions have to be fulfilled-the so-called ‘tricks’ of the specialist-in order to obtain the best possible results.