Science of Synthesis Knowledge Updates 2011 Vol. 1 (eBook)

Erick M. Carreira, Jozef Drabowicz, Kazuaki Ishihara, Jie Jack Li, Eric Jim Thomas (Herausgeber)

eBook Download: EPUB

2014 | 1. Auflage
572 Seiten
Thieme (Verlag)
978-3-13-178721-7 (ISBN)

Infos

The Science of Synthesis Editorial Board,together with the volume editors and authors, is constantly reviewing the whole field of synthetic organic chemistry as presented in Science of Synthesis and evaluating significant developments in synthetic methodology. Four annual volumes updating content across all categories ensure that you always have access to state-of-the-art synthetic methodology.

Content of this volume: Dialkyl- and Diarylmagnesiums, 1H- and 2H-Indazoles, Quinolizinium Salts and Benzo Analogues, 1,2-Diselenins, 1,4-Diselenins, Pyrimidines, Acyclic Dialkyl Selenoxides and Derivatives.

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7.6.15 Product Subclass 15: Dialkyl- and Diarylmagnesiums

L. Yang and C.-J. Li

Synthesis of Product Subclass 15

7.6.15.1 Method 1: Disproportion of Grignard Reagents

Grignard reagents (R1MgX),[1] which are a powerful tool in organic and organometallic chemistry,[2–6] have been found to exist in equilibrium with the corresponding magnesium halides and diorganomagnesium compounds in diethyl ether (▶ Scheme 1).[7] By adding a certain amount of an organic base, such as 1,4-dioxane,[8–11] pyridine,[12] or a glyme,[13] to a solution of a Grignard reagent, the equilibrium can be shifted to the right-hand side due to the precipitation of an insoluble magnesium halide/organic base adduct.

▶ Scheme 1 Schlenk Equilibrium of a Grignard Reagent with a Diorganomagnesium Reagent[7,10]

The Schlenk equilibrium is also affected by other factors, including the use of different substituent groups (R1),[14,15] halogens, temperatures, and so on. For example, the yield of the diorganomagnesium compound can be increased by using an organomagnesium chloride rather than an iodide at a relatively high temperature.[16] The approach offers a simple and general method for the preparation of symmetrical diorganomagnesium compounds and, after the separation of the magnesium halide/organic base adduct precipitates by filtration or centrifugation, a clear solution of the diorganomagnesium compound may be obtained. This solution is used directly in most cases and it can also be concentrated under vacuum to give the pure product. Diorganomagnesium compounds prepared by this method, such as di-tert-butylmagnesium (1) contain a trace amount of halides, and this can be avoided by preparation using diorganomercury(II) compounds and magnesium metal (see ▶ Section 7.6.15.3).

Di-tert-butylmagnesium (1); Typical Procedure:[10]

A soln of t-BuMgCl was prepared in the usual way,[17] with Et2O being used as the solvent, and was determined to be 0.0144 M with respect to t-BuMgCl and 0.0038 M with respect to MgCl2. The Grignard reagent soln (30 mL) was transferred by syringe into a centrifuge tube through a serum cap. Dry 1,4-dioxane (3.7 g, 0.042 mol) was added to the vigorously stirred soln, immediately producing a white precipitate. The centrifuge tube was then spun at 3000 rpm for 30 min. The supernatant soln was transferred by syringe to a N2-filled flask and was determined to be 0.36 M with respect to t-Bu (determined as 2-methylpropane), 0.177 M with respect to Mg, and 0.007 M with respect to Cl−.

7.6.15.1.1 Variation 1: Reaction of Magnesium Metal with 2-Chlorobutane

The direct reaction of magnesium metal with 2-chlorobutane cannot be induced under solvent-free conditions or in a hydrocarbon solvent, even at elevated temperatures. Addition of a limited amount of an ether to the mixture in a hydrocarbon solvent allows the direct reaction to proceed and good yields of the products to be obtained. For example, di-sec-butylmagnesium (2) is obtained from 2-chlorobutane and magnesium in cyclohexane in the presence of dimethyl ether (▶ Scheme 2).[18] The ether can be removed through codistillation with a hydrocarbon solvent (benzene or cyclohexane) or by vacuum stripping until dry and subsequent redissolution, which shifts the Schlenk equilibrium to the right because of the insolubility of magnesium chloride in the hydrocarbon solvent. A particularly reactive form of magnesium is needed for the direct reaction of secondary halides in a hydrocarbon with a limited amount of ether, as well as for the reaction of primary halides in the hydrocarbon alone. This reactive form is obtained by stirring commercially available magnesium powder with butyllithium in hexane overnight.

▶ Scheme 2 Reaction of Magnesium Metal with 2-Chlorobutane[18]

Di-sec-butylmagnesium (2); Typical Procedure:[18]

Mg turnings (2.43 g, 0.100 mol) and a few crystals of I2 were placed in a 500-mL flask fitted with a thermometer, mechanical stirrer, dry ice condenser, and dropping funnel. Enough Me2O, dried by passage over silica gel, was condensed into the flask to cover the turnings, and s-BuCl (1 mL) was added. A few drops of 1,2-dibromoethane were added to begin the reaction, and then the remainder of 100 mL of Me2O was condensed into the flask at –25°C. The remainder of 9.3 g (0.10 mol) of s-BuCl was then added, followed by gradual addition of cyclohexane (100 mL). The resulting mixture was allowed to warm slowly to rt and was then stirred at this temperature for 2 d, during which time a white slurry was observed to form. The mixture was then heated to 45°C for 2 h and allowed to cool and settle overnight. Analysis of the clear supernatant soln showed 0.77 M total base and 0.085 M Cl− content; yield: 78–80%.

7.6.15.2 Method 2: Reaction of Grignard Reagents with Organolithium Reagents

The preparation of both symmetrical and unsymmetrical diorganomagnesium compounds has been reported via the reaction of Grignard reagents and organolithium reagents in an ether/hydrocarbon solution.[19] The removal of all but 0.01% of the ether can be realized by the addition of hydrocarbon and removal of ether by distillation in a continuous manner.[20] The ethereal solution of diorganomagnesium prepared in this way contains little halogen [i.e., a halide/base (Mg2+) ratio of ca. 0.02:1] and in a hydrocarbon solution contains essentially no halogen at all. The process is satisfactory for most cases where the alkyl or aryl groups are of sufficient solubility, and diphenylmagnesium (3) can be obtained from phenylmagnesium bromide and phenyllithium using this system (▶ Scheme 3).[21]

▶ Scheme 3 Reaction of Phenylmagnesium Bromide with Phenyllithium[21]

Diphenylmagnesium (3); Typical Procedure:[21]

A soln of PhMgBr was prepared from Mg turnings (12.5 g, 0.514 mol), bromobenzene (52.5 mL, 0.500 mol), and anhyd Et2O (ca. 300 mL) and determined to be 1.50 M by total alkalinity, 1.59 M by Mg analysis, and 1.52 M by Br– determination (average: 1.536 M). A soln of PhLi was prepared from Li chips (7.5 g, 1.08 mol), bromobenzene (52.5 mL, 0.500 mol), and anhyd Et2O (400 mL) and determined to be 1.075 M by total alkalinity. Volumes of each of these solutions containing PhMgBr (0.40 mol) and PhLi (0.40 mol), respectively, were measured accurately under argon with the same graduated cylinder and then mixed and stirred magnetically. The resulting mixture, which became warm, was stirred at rt for 4.5 h. Titration of an aliquot indicated a total alkalinity of 1.40 M and a Mg content of 1.395 M. The Et2O soln was concentrated to dryness under vacuum and the residual Ph2Mg•2OEt2 complex was extracted with anhyd argon-saturated toluene (500 mL). Analysis of the toluene soln indicated a total alkalinity of 0.99 M, a Mg content of 1.01 M, and a Br– content of 0.005 M resulting in a Mg/Br ratio of 100:1.

7.6.15.2.1 Variation 1: Reaction of Activated Magnesium Halides with Organolithium Reagents

The exchange reaction of magnesium halides with organolithium reagents yields diorganomagnesium compounds. Ordinary commercially available anhydrous magnesium chloride and alcohol-treated magnesium chloride give only low conversions of sec-butyllithium into di-sec-butylmagnesium (2), even in the presence of a large excess of the finely powdered salt. However, activated magnesium chloride, obtained as a solid byproduct from the reaction of sec-butylmagnesium chloride with benzyl chloride or chlorine, or from the reaction of 1-chloropentane with magnesium, gives a high yield of di-sec-butylmagnesium in solution by reaction with sec-butyllithium (▶ Scheme 4).[18]

▶ Scheme 4 Reaction of Activated Magnesium Chloride with sec-Butyllithium[18]

Di-sec-butylmagnesium (2):[18]

Following the procedure of Glaze and Selman,[22] the product mixture from direct reaction of 1-chloropentane with Mg was extracted several times with benzene (CAUTION: carcinogen) to leave a solid residue of activated MgCl2. A 1.3 M soln of sec-butyllithium in cyclohexane (20 mL) was added to a slurry of this activated MgCl2 (4.8 g, 50 mmol) in benzene (10 mL) in a centrifuge tube fitted with a rubber septum. The mixture, which became warm initially and then cooled while being shaken for 10–15 min, was centrifuged. The supernatant soln was determined to contain 1.10 M total base, 1.02 M active alkyl, 0.55 M Mg, and 0.003 M Cl−; yield: 90–95%.

7.6.15.3 Method 3: Reaction of Diorganomercury(II) Compounds with Magnesium Metal

The diorganomagnesium compounds prepared from Grignard reagents or organolithium reagents (see ▶ Section 7.6.15.2) are almost always contaminated by a trace amount of halides or lithium, and the removal of solvated ethers from the...

Produkt-Details

• Erscheint lt. Verlag: 14.5.2014
• Verlagsort: Stuttgart
• Sprache: englisch
• Themenwelt: Naturwissenschaften ► Chemie ► Organische Chemie
• Themenwelt: Technik
• Schlagworte: 1 • 1H-Indazoles • 1H-INDAZOLE S • 2-Diselenins • 2H-Indazoles • 4-Diselenins • Acyclic Dialkyl Selenoxides • Benzo Analogues • Chemie • Chemische Synthese • chemistry of organic compound • chemistry organic reaction • chemistry reference work • chemistry synthetic methods • Compound • compound functional group • compound organic synthesis • Dialkylmagnesiums • Diarylmagnesiums • Functional Group • Mechanism • Method • methods in organic synthesis • methods peptide synthesis • Organic Chemistry • organic chemistry functional groups • organic chemistry reactions • organic chemistry review • organic chemistry synthesis • ORGANIC CHEM ISTRY SYNTHESIS • organic method • organic reaction • organic reaction mechanism • ORGANI C REACTION MECHANISM • Organic Syntheses • organic synthesis • organic synthesis reference work • Organisch-chemische Synthese • Organische Chemie • Peptide synthesis • Practical • practical organic chemistry • Pyrimidines • quinolizinium salts • Reaction • reference work • Review • review organic synthesis • review synthetic methods • REVIEW SYNTHE TIC METHODS • Selenoxides • Synthese • Synthetic chemistry • Synthetic Methods • Synthetic Organic Chemistry • synthetic transformation
• ISBN-10: 3-13-178721-X / 313178721X
• ISBN-13: 978-3-13-178721-7 / 9783131787217