A Grignard Reaction

consider the formation of an aryl Grignard reagent with a substituent para to the Br, will it proceed if the substituent is a tert-butyl ((CH3)3C-)

Yes

consider the formation of an aryl Grignard reagent with a substituent para to the Br, will it proceed if the substituent is an ester (OEt)

Yes

Mg may react with air to form

an MgO coating - scrape turnings before adding to expose fresh Mg or add iodine

Epoxides (Oxiranes)

an unusually reactive class of cyclic ethers due to the strong driving force associated with the relief of angular distortion (Baeyer strain) which accompanies the opening of the three-membered rings they contain (ethers are not typically attacked by nucleophiles)

anhydrous conditions

anhydrous diethyl ether (stored over sodium metal), glassware dried using a heating gun, drying tube (plugged with cotton and anhydrous CaCl2) attached to reaction flask

reaction scheme

bromobenzene + magnesium (in anhydrous diethyl ether) = phenylmagnesium + 4-chlorobenzaldehyde = 4-chlorobenzhydrol (final product)

Caution

bromobenzene is an irritant, measure it out in the hood and avoid breathing its vapor

Carbonation of Grignard Reagent

by passing carbon dioxide gas into a solution of grignard reagent or by pouring the grignard reagent over dry ice

organometallic compounds

compounds that contain carbon-metal bonds (not all organic compounds that have a metal attached)

Waste

ether: non-halogenated chromic acid test: heavy metal all other: halogenated

not reactive with grignard reagents

ethers, simple alkenes, aromatic hydrocarbons, and non-terminal alkynes *terminal alkynes are unusually acidic and will be abstracted by Grignard reagents)

grignard reagents are

excellent nucleophiles

caution must be taken when creating grignard reagents due to the exothermic reaction and a solvent which is both highly volatile and highly flammable

should be performed using a very efficient reflux condenser, and always have an ice bath standing by to cool the reaction flask if it becomes necessary to moderate a reaction that threatens to become too vigorous

reactive with grignard reagents

sulfonic acids (-SO3H), cyano groups, and nitro groups

consider 1H NMR of 4-chlorobenzhydrol in CDCl3, if you were to run the NMR in D2O instead, what major change would you expect to see in the spectrum

the H in the alcohol group will not be represented by a peak in the NMR

Do not obtain ether until

the instructor says it is safe to do so (all heat sources have been removed)

consider 1H NMR of 4-chlorobenzhydrol in CDCl3 how many non-equivalent hydrogens would be observed in the spectrum?

7

order of reactivity of alkyl or aryl halides with magnesium turnings/shavings

I > Br > Cl > F (fluorides rarely used, and special conditions are necessary)

suppose you wish to form 4-ethyl-2-phenyl-2-hexanol using a different bromo (not bromobenzene) compound and a different carbonyl (not 4-ethyl-2-hexanone)

MeBr and 1-phenyl-3-ethyl-1-pentanone could be used

if the formation of a grignard reagent does not begin spontaneously when Mg metal and a solution of an alkyl halide ether are mixed, one sometimes adds a small amount of iodine to the flask. What substance is formed from the reaction of iodine and magnesium? Is the iodine acting as an oxidizing or reducing agent?

MgI2 is formed. Iodine is the oxidizing agent

consider the formation of an aryl Grignard reagent with a substituent para to the Br, will it proceed if the substituent is HCC-

No

consider the formation of an aryl Grignard reagent with a substituent para to the Br, will it proceed if the substituent is a phosphonate (HOHOP=O)

No

limitations of grignard reactions

they are reactive with many functional groups

why is the product washed with aqueous NaOH?

to remove any phenols (Ar-OH) that may have formed

rearrangement process are

uncommon during grignard reactions

what is distilled off during the simple distillation

water (mainly), unreacted bromobenzene and 4-chlorobenzaldehyde, small amounts of benzene, and biphenyl (Ph-Ph)

Grignard reagent

organomagnesium halides which are commonly prepared by a reaction between magnesium metal and an alkyl or aryl halide

the C-Mg bond is quite polar with an electron-rich carbon and electron-poor magnesium

it acts as an extremely powerful base and will easily deprotonate any organic compound containing an OH or NH bond (reactions must be carried out under rigidly anhydrous conditions)

why is diethyl ether used as the solvent

it is unreactive with grignard reagents and grignard reagents are soluble in it

suppose you wish to form 4-ethyl-2-phenyl-2-hexanol and used bromobenzene as one of the starting compounds, what other compounds would be required in the preparation of this compound by a Grignard synthesis

magnesium and 4-ethyl-2-hexanone