Metalation with ethylmagnesium bromide

Under the action of strong organometallic bases, thiazole undergoes hydrogen-metal interconversion. Ethylmagnesium bromide reacts at 0°C with thiazole in ether to form an insoluble adduct that upon heating evolves ethane almost quantitatively and affords an etheral solution of thiazol-2-ylmagnesium bromide (155) (12). Proof of the structure of this... 

Acetylenic carbinols are prepared by the interaction of sodium acety-lides or acetylenic Grignard reagents with aldehydes. The formation and reaction of the metallic acetylide may be combined into a single operation. For example, an alkylacetylene in ether solution is treated successively with ethylmagnesium bromide and formaldehyde to give the acetylenic alcohol such as 2-heptyn-l-ol (82%). ... 

Thioureas are metallated by ethylmagnesium bromide [30 Eq. (23)]. The magnesium-thiourea is then converted to a carbodiimide by reaction with carbon disulfide. Lithium-thioureas can also be used, but give good yields only with bulky substituents on the thiourea. Less hindered lithio-thioureas undergo reaction to give isothiocyanates, which the magnesio-derivatives do not. 

Generally speaking, other cyclopentadienylmetal complex catalyzed carbo-metallations of alkynes are rather rare but a few interesting examples have been reported. The first one is the zirconocene 1 catalyzed ethylmagnesation of dialkyldiynes with ethylmagnesium bromide to afford a mixture of isomeric enynes 34 (Scheme 14). The ethylation proceeds regioselectively on the terminal carbon atom of the diyne moiety. However, the addition is not stereoselective a mixture of cis and trans isomers is obtained [22]. 

Ghromium trichloride tri(tetrahydrofuranate) stirred under Ng into tetra-hydrofuran, treated dropwise at —20° with ethylmagnesium bromide in tetra-hydrofuran, the resulting clear triethglchromium soln. treated at —20° with 2-butyne, and allowed to stand 3 days at room temp. hexamethylbenzene. Y 60% based on chromium compound.—These condensations are considered to proceed via acetylenic yr-complexes of chromium and are useful as a general synthetic method. F. e. s. W. Herwig, W. Metlesics, and H. Zeiss, Am. Soc. 81, 6203 (1959) with metal carbonyl compounds, particularly [Go(GO)4]2Hg, s. W. Hiibel and G. Hoogzand, B. 93, 103 (1960). 

N-Unsubstituted azomethine ylides may be generated thermally (79), and the N-metalated, 2-azaallyl anion versions may be generated by action of nonmetalhc bases such as l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) on certain imines (80). Although they are assumed to show similar chemical properties, these two species usually show different reaction patterns, as shown in Scheme 11.7, where the regio-and stereoselectivities of the cycloadditions are quite different (24,78-80). Metala-tion of (alkylideneamino)acetonitriles can be performed with metallic bases other than LDA. Thus, butyllithium, ethylmagnesium bromide, and magnesium bromide-diisopropylamide are also effective (78). The N-magnesioazomethine... 

A method for generating a perfluoroarylmagnesium compound is the cleavage of a pentafluorophenyl-metal bond by a nucleophile such as ethylmagnesium bromide As an example, tetrakis(pentafluorophenyl)tin on reaction with ethyl-magnesium bromide gives a series of products, one of which may result from pentafluorophenylmagnesium bromide [27] (equation 7)... 

Metalation of unsymmetrical mines. Pioneering studies on the metalation and subsequent alkylation of unsymmetrical imines indicated that the reaction occurs predominantly at the less substituted a-position.5 This pattern has since been observed generally with lithium diethylamide, LDA, and ethylmagnesium bromide. Recent studies6 indicate that the site of alkylation is independent of the alkylating group but is dependent on the substituent on the imine and particularly on the basicity of the base. Butyllithium ( -, sec-, and /-) can abstract a proton from the more substituted a-carbon of the acyclic imine 1 to some extent. In the case of the cyclic imine 2, alkylation at the more substituted position is actually the main reaction. However, only substitution at the less substituted position of the dimethylhydrazone of 2-methylcyclohexanone is observed with either LDA or jcc-butyllithium (7,126-128). 

Compound 1 has also been prepared by the following methods. Addition of ethylmagnesium bromide to the protected cyanohydrin of acetone, followed by hydrolysis and silylation provides 1 1n 40t yield (eq 2).2 Metallation of 1-methoxypropene by butyllithium in pentane gives 1-lithio-l-methoxypropene, which reacts with acetone to give, after hydrolysis and silylation, ketone 1... 

A 1 litre three-necked round-bottomed flask is equipped with a gas inlet tube, a mechanical stirrer, and an efficient reflux condenser (in the case of volatile acetylenes, a solid carbon dioxide-acetone cold finger condenser) with the top of the condenser connected to a cold trap, and furnished with an inert atmosphere. (CAUTION particularly in the case of volatile acetylenes, all connections, and the stirrer seal, must be gas-tight). The alkyne (0.5-0.6 mol) is introduced into a solution of ethylmagnesium bromide (approximately equimolar) in ether or THF, as a gas or from the dropping funnel, under the conditions summarized in Table 3.5 this table also specifies the conditions required to complete the metallation. 

A solution of 2-(pyrazol-l-yl)phenylmagnesium bromide in THF (350 ml) is prepared by metallation of 1-phenylpyrazole (86.5 g, 0.6 mol) by ethylmagnesium bromide [9] and stirred and maintained at 25-30° as a solution of benzonitrile (51.6 g, 0.5 mol) in THF (150 ml) is added rapidly. The mixture is heated under reflux for 6 h, cooled, and poured into a solution of ammonium chloride (120 g) in water (1 litre). The solution is extracted with ether, and the ether phase is extracted with 2 m hydrochloric acid (total 600 ml). (Evaporation of the ether phase then leaves 1-phenylpyrazole (40 g)). The acid extract is (without filtration from the crystals which precipitate) treated with 10 m sodium hydroxide (300 ml) and extracted with ether. Evaporation of the extract gives phenyl 2-(pyrazol-l-yl)phenyl ketimine (99 g, 80% based on benzonitrile), m.p. 106-107°. 

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