Preparation Grignard reagents

Anilides and a-Naphthalides. The Grignard reagents prepared from alkyl halides react with phenyl isocyanate (CgHjN=C=0) or with a-uaphthy l isocyanate (C,oH, N=C=0) to yield addition products that are converted by hydrolysis into anihdes and a-naphthalides respectively RX + Mg —> RMgX... 

Alkyl mercuric halides. Grignard reagents, prepared from alkyl halides, react with a mercuric halide that contains the same halogen as the reagent to form alkyl mercuric halides ... 

After the air in the flask had been replaced completely with nitrogen, 100 ml of dry diethyl ether, 0.20 mol of the cumulenic ether (see Chapter V, Exps. 7, 8 and 11) and 1 g (note 1) of copper(l) bromide were placed in it. A solution of the Grignard-reagent, prepared from 0.50 mol of the chloride (see Chapter II,... 

Metalloid azoles frequently show expected properties, especially if not too many heteroatoms are present. Thus Grignard reagents prepared from halogen-azoles (see Section 4.02.3.9.3) show normal reactions, as in Scheme 60. 2-Lithioimidazoles react normally, e.g. with acetaldehyde (Scheme 61) (70AHC(12)103) 5-lithioisothiazoles (see Scheme 62) (72AHC(14)1) and 2-lithiothiazoles undergo many of the expected reactions. 

A solution of 6.3 g (0.9 moles) ethoxyacetylene in 50 ml ether is added dropwise during 30 min to a Grignard reagent prepared from 2.18 g (90 mg-atoms) magnesium and 9.81 g (90 mmoles) ethyl bromide. The reaction mixture is stirred for 1 hr at room temperature and then a solution of 3 g (9 mmoles) 3) -acetoxyandrost-5-en-I7-one in 50 ml dry ether is added dropwise. The mixture is refluxed for 1 hr and after cooling to 0° poured into 100 ml of an aqueous ammonium chloride solution. The aqueous solution is extracted with ether, and the organic extract is washed with ammonium chloride solution and water, dried, and evaporated. The residue is chromatographed on 130 g alumina (activity III). Elution with petroleum ether-benzene (1 1) yields, after crystallization from acetone-hexane, 1.27 g (35%) 3j5-acetoxy-17a-ethoxyethynylandrost-5-en-17) -ol mp 138-139° Ho -122°. 

An alternate scheme for preparation of the last drug involves first bromination of the methylene group on 33 (obtainable by several methods from 27). A displacement reaction of the Grignard reagent prepared from 34 on 2-dimethylaminoethyl chloride affords again amytriptylene (32). ... 

The solution of the Grignard reagent prepared in (A) was cooled to 5° to 10°C and stirred while 22.7 g (0.11 mol) of dibenzo[a,e] cycloheptatrien-5-one was added in portions. After stirring for 1 hour during which time the reaction mixture was allowed to warm up to room temperature, the bulk of the tetrahydrofuran was distilled at 40° to 50°C under reduced pressure. Benzene, 150 ml, was added and the reaction mixture stirred and cooled in an ice-bath while water, 100 ml, was added gradually. The benzene layer was separated by decantation and the gelatinous residue extracted three times with 75 ml portions of boiling benzene. 

The 1-hydroxycyc(openty(-(o-ch(orophenyl)-ketone N-methylimine used as an intermediate is prepared as follows. To the Grignard reagent prepared from 119.0 g of cyclopentyl... 

To the Grignard reagent prepared from 0.59 part of magnesium, 3.95 parts of bromobenzene... 

Method B 1.5 mmol of Cul are added to a solution of 1.06 mmol of the substrate in 15 mL of Lt20 at 0 C under argon. After 30 min, 3.07 mmol of the Grignard reagent, prepared in Ei20, are added dropwise with stirring. After 1 h the reaction is worked up as above. 

The Grignard reagent prepared from chloromethyltrimethylsilane (30 mmol) and Mg (36 mg atom) in ether (20 ml) was added dropwise to diphenyl phosphorazidate (27 mmol) in ether (40 ml), keeping the temperature below 0°C. The reaction mixture was stirred for 2 hat 0 C, and then at ambient temperature for 3 h. It was then cooled to 0 °C, and ice-water was added. The mixture was filtered, and the solid was washed with ether. The combined ethereal extracts were washed with ice-water and dried. Careful concentration at <45 °C/atmospheric pressure, then distillation at... 

Boiling-point elevation and freezing-point depression measurements have demonstrated that at all concentrations in THF and at low concentrations in ether (up to 0.1M) Grignard reagents prepared from alkyl bromides and iodides are monomeric, that is, there are few or no molecules with two magnesium atoms. Thus, part of the Schlenk equilibrium is operating... 

However, Grignard reagents prepared from alkyl bromides or iodides in ether at higher concentrations (0.5-1 M) contain dimers, trimers, and higher polymers, and those prepared from alkyl chlorides in ether at all concentrations are dimeric, so that 24 is in solution, probably in equilibrium with RMgX and R2Mg that is, the complete Schlenk equilibrium seems to be present. 

The Grignard reagents prepared from the activated magnesium appear to react normally with electrophiles. Thus reactions with proton donors, ketones, and carbon dioxide afford hydrocarbons, alcohols, and carboxylic acids, respectively. The reductive coupling of ketones to pinacols had also been accomplished with the activated magnesium. ... 

Alternatively, add a solution of 4 5 g. of p-toluidine in dry ether to the Grignard reagent prepared from 1 0 g. of magnesium as detailed above. Then introduce 1 - 0 g. (or 0-02 mol) of the ester and proceed as described lOr anilides. 

This potent inhibitor of cholesterol biosynthesis has been synthesized178 by one-pot esterification of the alcohol 210 with the acid chloride of 2,2-dimethylbutanoic[l-14C] acid, obtained by carbonation of the Grignard reagent prepared from 2-chloro-2-methylbutane (equation 74). Desilylation of 211 afforded [14C]simvastatin 209 in 29% radiochemical yield from 14C-labelled C02. This 14C-labelled drug was needed for elucidation of its metabolic fate in experimental animals. 

Addition of the Grignard reagent, prepared from 3-aryl-2-/.sopropyl-1 -chloropropane (340) to nitrone (339) is a very important step toward the synthesis of compound (342a) which is used in preparing the antihypertensive agent SPP-100B and its epimer (342b) (Scheme 2.143) (197). 

To the Grignard reagent prepared from 2.4 g Mg, 10 ml anisole and 16 g ethyl iodide, add 7.8 g indole in 10 ml anisole. Stir and cool to 0°. Slowly add dropwise 5.5 g Cl-acetonitrile in 40 ml anisole. Warm to room temperature and stir heat to 60-70° on water bath (a reddish precipitate forms over about twenty minutes). Cool and purify and convert to the dialkyltryptamine as described earlier. Tryptamines JOC 24,894(1959)... 

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