Methyl magnesium

Note that ethylene oxide reacts with the Grignard reagent to gi e a 2-substi tuted ethanol e.g. with methyl magnesium iodide ... 

Dimethyl ethyl carbinol (2-methy 1-2-butanol or amyl alcohol), CH3CHjCOH(CH3).2. From ethyl propionate and methyl magnesium iodide. Collect the tertiary alcohol at 100-102°. 

The rate of the reaction decreases with increasing number of substituents in the acetylenic halide, and it is higher with acetylenic bromides than with the corresponding chlorides. Methyl magnesium iodide gives equal amounts of 1,1- and 1,3--substitution products, whereas tert.-butylmagnesium bromide does not react. However, for some tert.-butyl substituted allenes there exists an attractive com-... 

Medroxyprogesterone acetate (74) is stmcturaHy related to and has been prepared from hydroxyprogesterone (39) (Fig. 10). Formation of the bis-ketal accomplishes the protection of the ketones and the required migration of the double bond. Epoxidation with peracetic acid produces a mixture of epoxides (75), with a predominating. Treatment of the a-epoxide with methyl magnesium bromide results in diaxial opening of the epoxide. Deprotection of the ketones provides (76), which is dehydrated to (77) by treatment with dilute sodium hydroxide in pyridine. Upon treatment with gaseous hydrochloric... 

Magnesium Methylate. Magnesium methoxide [109-88-6] Mg(OCH2)2, mol wt, 86.3, is an almost white powder powder density 0.5 g/mL ... 

The present procedure was developed from those of Wallach and Freylon, based upon the general method discovered by Leuckart. a-Phenylethylamine also can be prepared satisfactorily by the reduction of acetophenone oxime with sodium and absolute alcohol or sodium amalgam, but the reagents are more expensive and the processes less convenient. The amine has been obtained by reducing acetophenone oxime electro-lytically, by reducing acetophenone phenylhydrazone with sodium amalgam and acetic acid, from a-phenylethyl bromide and hexamethylenetetramine, and by the action of methyl-magnesium iodide upon hydrobenzamide, as well as by other methods of no preparative value. 

Rao prepared 2a-methyl-5a-cholestan-2i -ol (5) by reaction of methyl-magnesium iodide with 5a-cholestan-2-one (4). The 2i -configuration of the hydroxyl group was established by converting (5) to the 2a-methyl-2j5,19-epoxide (6) with lead tetraacetate and iodine in boiling benzene. 

Methyl steroids (67) are obtained by reaction of an excess of methyl-magnesium halide with various pregnan-20-ones (66). ... 

A slow stream of purified and dried acetylene is passed for 3 hr through a solution containing 25 ml (75 mmoles) of a 3 TV solution of methyl magnesium bromide and 100 ml of anhydrous tetrahydrofuran. A solution consisting of 5 g (17 mmoles) of 3)5-hydroxyandrost-5-en-17-one and 50 ml of anhydrous tetrahydrofuran is then added and the mixture is boiled at reflux for 15 min, during which time a heavy precipitate forms. The reaction mixture is cooled and poured into 1 liter of water containing 20 ml of concentrated sulfuric acid. The crude product is obtained as a precipitate, which is filtered, washed with water and dried to yield 5.2 g of 17a-ethynylandrost-5-ene-3, 17 -diol mp 228-232°. One crystallization from chloroform-hexane yields 4.5 g (83%) mp 238-240° [[Pg.73]

The 1 l)5-hydroxyl group in the A -3-ketone (33) favors attack towards the j -face of the molecule, possibly due to complex formation with the methyl-magnesium halide. Thus, the )5-methyl isomer (34), is obtained as the major product in 22% yield after reacetylation. 

Epoxide (88) is converted to C-norpregnane (89) in 60% yield by methyl-magnesium iodide in refluxing ether-benzene. No rearrangement to the C-norsteroid occurs with dimethylmagnesium. 

Formyl- and 4-bromo-3-formyl-isothiazole have been prepared in good yield from the dibromomethyl compounds obtained by side-chain halogenation of the appropriate 3-methylisothiazole with N-bromosuccinimide. 3-Acetyl- and 3-acetyl-4-bromo-isothiazole have been prepared from the 3-cyanoisothiazoles and methyl magnesium iodide. ... 

Conjugate addition of methyl magnesium iodide in the presence of cuprous chloride to the enone (91) leads to the la-methyl product mesterolone (92) Although this is the thermodynamically unfavored axially disposed product, no possibility for isomerization exists in this case, since the ketone is once removed from this center. In an interesting synthesis of an oxa steroid, the enone (91) is first oxidized with lead tetraacetate the carbon at the 2 position is lost, affording the acid aldehyde. Reduction of this intermediate, also shown in the lactol form, with sodium borohydride affords the steroid lactone oxandrolone... 

An ester of alanine with an arylaliphatic alcohol has shown promise as a non-tricyclic antidepressant. It may be speculated that the hindered milieu of the ester linkage protects the compound from hydrolysis by endogenous esterases. The preparation starts by reaction of pheny-lacctate 83 with methyl magnesium iodide to give tertiary carbinol 84. Acylation with 2-bromo-]>ropionyl bromide leads to ester 85 displacement of halogen with ammonia leads to alaproclate ( 6) [211. 

Wallach has prepared a-phellandrene synthetically from sabinenic acid by oxidising it to sabina ketone with potassium permanganate. This ketone was converted into its semicarbazone, and the latter compound treated with dilute sulphuric acid, when sabina ketone is not regenerated, but an isomer, which was found to be isopropyl-hexenone. By the interaction of this body with methyl-magnesium iodide, loss of water occurs with a simultaneous conversion into a-phellandrene, which appears to be a mixture of the dextro- and laevo- varieties. This syntheticallj prepared a-phellandrene has the following characters —... 

To an ethereal solution of methyl magnesium iodide prepared from 26.7 g (1.1 mols) of magnesium and 160 g (1.13 mols) Of methyl iodide in 200 cc of dry ether, is added a solution of 79 g (0.72 mol) of cyclopentylacetonitrile in 100 cc of dry ether. The reaction mixture is refluxed for 4 hours. The reaction mixture is then decomposed with ice in the usual way, and the ether layer containing the cyclopentylacetone is separated, is dried over anhydrous magnesium sulfate and the ether removed by evaporation. The residue comprising cyclopentylacetone is purified by distillation in vacuo. The cyclopentylacetone boils at 82° to 84°C at about 32 mm pressure. 

J/3,5a,6(3- Trihydroxy-6oi, 17a-Dimethyl-17 -Carbometboxyandrostane (IV) 3(3-Acetoxy-5a-hydroxy-17a-methyl-17/3-carbomethoxyandrostan-6-one (III, 1.004 g) is dissolved in dry benzene (25 ml) and methyl magnesium bromide solution in ether (3M, 10 ml) is added. 

Alternatively, 25.0 g of either 3j3,5a-dihydroxy-17a-methyl-17j3-carbomethoxyandrostan-6-one (Ilia) or 25.0 g of its 3)3-acetate (Hlb), are dissolved in dry tetrahydrofuran (1,250 ml, freshly distilled over lithium aluminum hydride) and dry benzene (2,000 ml) is added. Methyl magnesium bromide in ether solution (3 M, 750 ml) is added to the stirred solution and the resulting mixture is stirred at room temperature for 16 hours. An additional quantity of methyl magnesium bromide solution in ether (2M, 375 ml) is added, and 1,250 ml of the solvent mixture are distilled off. The resulting mixture is refluxed for 5 hours and worked up as described above, yielding compound (V) as a colorless oil. 

Hydroxyprogesterone Methyl magnesium bromide Sulfuric acid... 

Preparation of 5a,17a-Dihydroxy-6 -Methylallopregnane-3,20-dione 3,20-Bis-fEthylene Ketal) To a solution of 91.6 g of 5a,6a-oxido-17a-hydroxyallopregnane-3,20-dione 3,20-bis-(ethylene ketal) in 3,500 ml of freshly distilled tetrahydrofuran was added 1,170 ml of commercial 3 molar methyl magnesium bromide in ether solution. The reaction mixture was boiled to remove 1,800 ml of solvent by distillation and thereafter 1,000 ml of freshly distilled tetrahydrofuran was added. 

In the present instance, the product is a tertiary alcohol with two methyl groups and one props7 group. Starting from a ketone, the possibilities are addition of methyl-magnesium bromide to 2-pentanone and addition of propylmagnesium bromide to acetone. 

A synthetically useful diastereoselectivity (90% dc) was observed with the addition of methyl-magnesium bromide to a-epoxy aldehyde 25 in the presence of titanium(IV) chloride60. After treatment of the crude product with sodium hydride, the yy -epoxy alcohol 26 was obtained in 40% yield. The yyn-product corresponds to a chelation-controlled attack of 25 by the nucleophile. Isolation of compound 28, however, reveals that the addition reaction proceeds via a regioselective ring-opening of the epoxide, which affords the titanium-complexed chloro-hydrin 27. Chelation-controlled attack of 27 by the nucleophile leads to the -syn-diastereomer 28, which is converted to the epoxy alcohol 26 by treatment with sodium hydride. 

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