User:PME36/sandbox/Phenylsodium

Phenylsodium C6H5Na is an organometallic compound which can be used to add phenyl groups to ketones, esters, and ethers as well as alkyl, aryl, and acyl halides. The existence of phenylsodium was originally proposed by Kekulé after observing the formation of sodium benzoate in the reaction of bromobenzene with sodium under carbon dioxide. The solid compound was first isolated by Acree in 1903. The reaction products of phenylsodium with various chemicals are nearly identical to those of Grignard reagents, but the Grignard reaction is far more commonly used likely due to the higher reactivity of phenylsodium and safety issues associated with the use of metallic sodium as a starting material. Attempts have been made successfully to improve the stability and solubility of phenylsodium through the use of magnesium alkoxides, organolithium compounds, and chelating agents.

Transmetallation
In the original synthesis, diphenylmercury and sodium metal are heated in benzene to yield a suspension of phenylsodium:
 * (C6H5)2Hg  +  3 Na   &rarr;   2 C6H5Na  +  NaHg

The Shorigen reaction is also used in the generation of phenylsodium, where an alkyl sodium compound is reacted with benzene: :
 * RNa + C6H6 &rarr; RH + C6H5Na

The method can also result in the addition of a second sodium. This dimetallation occurs in the meta and para positions. The use of certain alkyl sodium compounds such as n-amyl sodium is known to greatly increase this dimetallation effect.

Metal-Halogen Exchange
Due to the dangers associated with organomercury compounds, other synthetic routes were adopted. The most commonly employed route for the synthesis of phenylsodium utilizes powdered sodium metal in benzene which is reacted with chlorobenzene:
 * C6H5Cl  +  2 Na   &rarr;    C6H5Na  +  NaCl

Bromobenzene may also be used, but the yield of phenylsodium tends to be lower than with chlorobenzene. The yield of this method is reduced by the formation of diphenyl due to phenylsodium reacting with aryl halide starting material
 * C6H5Na +  C6H5Cl &rarr; (C6H5)2 + NaCl

Lithium Exchange
A more modern approach to the synthesis of phenylsodium involves the use of phenyllithium and NaOtBu in the reaction:
 * C6H5Li + NaOtBu &rarr; C6H5Na + LiOtBu

Properties and Structure
The first syntheses of phenylsodium which employed the organomercury route seemed to yield a light brown powder. It was discovered by Schlenk that this product was contaminated by a sodium amalgum. Centrifugation allowed for the isolation of pure phenylsodium which appears as a yellowish-white amorphous powder which readily bursts into flames.

Like phenyllithium, adducts of of the compound with PMDTA can be isolated. While phenyllithium forms a monomeric adduct with PMDTA, phenylsodium exists in the dimeric form NaPh[PMDTA]2. This is due to sodium's larger ionic radius allowing for a coordination number of 5 adopting a distorted trigonal bipyramidal geometry.

Phenylsodium's high reactivity and insolubility make it difficult to store for later use. Complexes of phenylsodium and magnesium alkoxides, especially magnesium 2-ethoxyethoxide Mg(OCH2CH2OEt)2, are able to solubilize phenylsodium. The complex is formed by the reaction:
 * NaPh + Mg(OCH2CH2OEt)2 &rarr; Na2MgPh2(OCH2CH2OEt)2

The complex is soluble in benzene, unlike phenylsodium. Although the phenylsodium is complexed, it maintains its phenylation and metalation ability. Additionally, the complex is highly stable in benzene retaining its reactivity after a month of storage.

Phenyllithium itself can also be used to modify the properties of phenylsodium. Ordinarily, phenylsodium reacts violently with diethyl ether, but Georg Wittig showed that by synthesizing PhNa with PhLi in ether, the complex (C6H5Li)(C6H5Na)n was formed. The phenylsodium component of the complex reacts before the phenyllithium, making it an effective compound to stabilize the highly reactive sodium compound. This complex could be isolated as solid crystals which were soluble in ether and remained stable in solution at room temperature for several days. Phenyllithium is able to stabilize phenylsodium in a ratio as high as 1:24 Li:Na, although this produces an insoluble mass which could be still used for reactions.

Reactions
Reactions involving phenylsodium as an intermediate were employed as early as the mid 19th century, although before 1903 the existence of the compound was purely hypothetical. Because of the instability in air, phenylsodium is prepared as a suspension by the methods discussed previously. The reagent of choice is then added, yielding the desired product. The reactions of phenylsodium are nearly identical to those of Grignard reagents with nucleophilic additions of phenyl to carbonyls and halides. The reactions with alkyl and aromatic halides are an example of the Wurtz-Fittig Reaction. The work of Acree provides a number of examples of reactions involving the compound.

Nucleophilic Additions
When reacted with alkyl halides, the halogen is substituted with a phenyl group such as in the reaction with bromethane producing ethyl benzene:


 * Ethyl bromide reaction with phenylsodium.svg

This reaction also occurs with aromatic halides and commonly occurs during the synthesis of the phenylsodium. As the sodium reacts with bromobenzene to produce phenylsodium, the phenylsodium combines with unreacted bromobenzene to produce diphenyl:


 * Reaction of phenylsodium with bromobenzene.svg

An interesting reaction involving benzyl chloride and phenylsodium results in the formation of diphenylmethane and stilbene. Diphenylmethane is the expected product from the substitution of chloride, but the formation of stilbene is unusual given the alkene linking the two benzyl groups. It is potentially formed through radical intermediates like those proposed in the Wurtz-Fittig reaction mechanism.


 * Benzyl chloride reaction with phenyl sodium.svg

The reaction of phenylsodium with benzoyl chloride demonstrates both the reaction with acyl chlorides and ketones. The chloride is first substituted with phenyl to produce benzophenone, which reacts with another equivalent of phenylsodium to yield triphenylcarbinol.


 * Benzoyl chloride reaction with phenylsodium.svg

Metallation
Metallation reactions with phenylsodium proceed in the following general form:
 * PhNa + RH &rarr; C6H6 + RNa

The metallation is confirmed/detected by treatment of the metallated compound with carbon dioxide, affording the corresponding sodium carboxylate which can be acidified to yield the carboxylic acid:
 * RNa + CO2 &rarr; RCO2Na

Metallation follows a generally predictable order of reactivity. Benzene can be metallated by alkylsodium compounds resulting in phenylsodium. The phenylsodium is then able to metallate other aromatic compounds. The most commonly used reagent for metallation by phenylsodium is toluene, producing benzylsodium. Toluene can be metallated by synthesizing phenylsodium in toluene instead of benzene:
 * C6H5Cl + 2Na + (C6H6)(CH3) &rarr; C6H6 + NaCl + (C6H6)(CH2)Na

The benzylsodium can then be used in a nucleophilic addition. The effectiveness of the metallation can be determined by carbonating and isolating the benzoic acid product.