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The Birch reduction is an organic reaction that is used to convert
arene Aromatic compounds, also known as "mono- and polycyclic aromatic hydrocarbons", are organic compounds containing one or more aromatic rings. The parent member of aromatic compounds is benzene. The word "aromatic" originates from the past grouping ...
s to
cyclohexadiene Cyclohexadiene may refer to: * 1,3-Cyclohexadiene, * 1,4-Cyclohexadiene, See also * Benzene or its theoretical isomer ''1,3,5-Cyclohexatriene'' * Cyclohexene Cyclohexene is a hydrocarbon with the formula C6H10. This cycloalkene is a colorl ...
s. The reaction is named after the Australian chemist Arthur Birch and involves the
organic reduction Organic reductions or organic oxidations or organic redox reactions are redox reactions that take place with organic compounds. In organic chemistry oxidations and reductions are different from ordinary redox reactions, because many reactions carr ...
of
aromatic ring In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satu ...
s in an
amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent suc ...
solvent (traditionally liquid
ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous wa ...
) with an
alkali metal The alkali metals consist of the chemical elements lithium (Li), sodium (Na), potassium (K),The symbols Na and K for sodium and potassium are derived from their Latin names, ''natrium'' and ''kalium''; these are still the origins of the names ...
(traditionally sodium) and a proton source (traditionally an
alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...
). Unlike catalytic
hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic c ...
, Birch reduction does not reduce the aromatic ring all the way to a cyclohexane. An example is the reduction of
naphthalene Naphthalene is an organic compound with formula . It is the simplest polycyclic aromatic hydrocarbon, and is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08  ppm by mass. As an aromati ...
in ammonia and ethanol:


Reaction mechanism and regioselectivity

A solution of sodium in liquid ammonia consists of the intensely blue electride salt a(NH3)xsup>+ e. The
solvated electron A solvated electron is a free electron in (solvated in) a solution, and is the smallest possible anion. Solvated electrons occur widely. Often, discussions of solvated electrons focus on their solutions in ammonia, which are stable for days, but s ...
s add to the aromatic ring to give a
radical anion In organic chemistry, a radical anion is a free radical species that carries a negative charge. Radical anions are encountered in organic chemistry as reduced derivatives of polycyclic aromatic compounds, e.g. sodium naphthenide. An example of a ...
, which then abstracts a proton from the alcohol. The process then repeats at either the ''ortho'' or ''para'' position (depending on substituents) to give the final diene. The residual double bonds do not stabilize further radical additions. The reaction is known to be third order – first order in the aromatic, first order in the alkali metal, and first order in the alcohol. This requires that the rate-limiting step be the conversion of radical anion B to the cyclohexadienyl radical C. That step also determines the structure of the product. Although Arthur Birch originally argued that the protonation occurred at the ''meta'' position, subsequent investigation has revealed that protonation occurs at either the ''ortho'' or ''para'' position. Electron donors tend to induce ''ortho'' protonation, as shown in the reduction of
anisole Anisole, or methoxybenzene, is an organic compound with the formula CH3OC6H5. It is a colorless liquid with a smell reminiscent of anise seed, and in fact many of its derivatives are found in natural and artificial fragrances. The compound is ma ...
(1). Electron-withdrawing substituents tend to induce ''para'' protonation, as shown in the reduction of
benzoic acid Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin, wh ...
(2).
Solvated electrons will preferentially reduce sufficiently electronegative functional groups, such as ketones or nitro groups, but do not attack
alcohols In chemistry, an alcohol is a type of organic compound that carries at least one hydroxyl () functional group bound to a saturated carbon atom. The term ''alcohol'' originally referred to the primary alcohol ethanol (ethyl alcohol), which is ...
,
carboxylic acids In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
, or ethers.


Secondary protonation regioselectivity

The second reduction and protonation also poses mechanistic questions. Thus there are three resonance structures for the carbanion (labeled B, C and D in the picture). Simple Hückel computations lead to equal electron densities at the three atoms 1, 3 and 5, but asymmetric bond orders. Modifying the exchange integrals to account for varying interatomic distances, produces maximum electron density at the central atom 1, a result confirmed by more modern RHF computations. * * The result is analogous to conjugated enolates. When those anions (but not the enol tautomer) kinetically protonate, they do so at the center to afford the β,γ-unsaturated carbonyl.


Modifications

Traditional Birch reduction requires
cryogenic In physics, cryogenics is the production and behaviour of materials at very low temperatures. The 13th IIR International Congress of Refrigeration (held in Washington DC in 1971) endorsed a universal definition of “cryogenics” and “cr ...
temperatures to liquify ammonia and
pyrophoric A substance is pyrophoric (from grc-gre, πυροφόρος, , 'fire-bearing') if it ignites spontaneously in air at or below (for gases) or within 5 minutes after coming into contact with air (for liquids and solids). Examples are organolith ...
alkali-metal electron donors. Variants have developed to reduce either inconvenience. Many amines serve as alternative solvents: for example,
THF Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water-miscible organic liquid with low viscosity. It is ma ...
or mixed ''n''-propylamine and
ethylenediamine Ethylenediamine (abbreviated as en when a ligand) is the organic compound with the formula C2H4(NH2)2. This colorless liquid with an ammonia-like odor is a basic amine. It is a widely used building block in chemical synthesis, with approximately 5 ...
. To avoid direct alkali, there are chemical alternatives, such as M-SG reducing agent. The reduction can also be powered by an external potential or sacrificial anode (magnesium or aluminum), but then alkali metal salts are necessary to colocate the reactants via complexation.


Birch alkylation

In Birch alkylation the
anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...
formed in the Birch reduction is trapped by a suitable
electrophile In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carri ...
such as a
haloalkane The haloalkanes (also known as halogenoalkanes or alkyl halides) are alkanes containing one or more halogen substituents. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalkanes are widely us ...
, for example: : In substituted aromatics, an electron-withdrawing substituent, such as a
carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
, will stabilize the carbanion to generate the least-substituted olefin; an electron-donating substituent has the opposite effect. :


Benkeser reduction

The Benkeser reduction is the
hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic c ...
of
polycyclic aromatic hydrocarbon A polycyclic aromatic hydrocarbon (PAH) is a class of organic compounds that is composed of multiple aromatic rings. The simplest representative is naphthalene, having two aromatic rings and the three-ring compounds anthracene and phenanthrene. ...
s, especially
naphthalene Naphthalene is an organic compound with formula . It is the simplest polycyclic aromatic hydrocarbon, and is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08  ppm by mass. As an aromati ...
s using lithium or
calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
metal A metal (from Greek μέταλλον ''métallon'', "mine, quarry, metal") is a material that, when freshly prepared, polished, or fractured, shows a lustrous appearance, and conducts electricity and heat relatively well. Metals are typica ...
in low molecular weight alkyl
amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent suc ...
s solvents. Unlike traditional Birch reduction, the reaction can be conducted at temperatures higher than the boiling point of ammonia (−33 °C). For the reduction of naphthalene with lithium in a mixed ethylamine- dimethylamine solution, the principal products are bicyclo .3.0ec-(1,9)-ene, bicyclo .3.0ec-(1,2)-ene and bicyclo .3.0ecane. The directing effects of naphthalene substituents remain relatively unstudied theoretically. Substituents adjacent to the bridge appear to direct reduction to the unsubstituted ring; β substituents (one bond further) tend to direct reduction to the substituted ring.


History

Arthur Birch, building on earlier work by Wooster and Godfrey, developed the reaction while working in the
Dyson Perrins Laboratory The Dyson Perrins Laboratory is in the science area of the University of Oxford and was the main centre for research into organic chemistry of the University from its foundation in 1916 until its closure as a research laboratory in 2003. Until 2 ...
at the University of Oxford. * * * * * * Birch's original procedure used sodium and ethanol; Alfred L. Wilds later discovered that lithium gives better yields. The reaction was difficult to understand mechanistically, with controversy lasting into the 1990s. The case with electron-withdrawing groups is obvious, because the Birch alkylation serves as a trap for the penultimate dianion D. This dianion appears even in alcohol-free reactions. Thus the initial protonation is ''para'' rather than ''ipso'', as seen in the B-C transformation. For electron-donating substituents, Birch initially proposed ''meta'' attack, corresponding to the location of greatest electron density in a neutral
benzene ring Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, ...
, a position endorsed by Krapcho and Bothner-By. These conclusions were challenged by Zimmerman in 1961, who computed electron densities of the radical and diene anions, revealing that the ''ortho'' site which was most negative and thus most likely to protonate. But the situation remained uncertain, because computations remained highly sensitive to transition geometry. Worse, Hückel orbital and unrestricted Hartree-Fock computations gave conflicting answers. Burnham, in 1969, concluded that the trustworthiest computations supported ''meta'' attack; Birch and Radom, in 1980, concluded that both ''ortho'' and ''meta'' substitutions would occur with a slight preference for ''ortho''. * * In the earlier 1990s, Zimmerman and Wang developed an experiment technique to distinguish between ''ortho'' and ''meta'' protonation. The method began with the premise that carbanions are much more basic than the corresponding radical anions and thus protonate less selectively. Correspondingly, the two protonations in Birch reduction should exhibit an isotope effect: in a protium–deuterium medium, the radical anion should preferentially protonate and the carbanion deuterate. Indeed, a variety of methoxylated aromatics exhibited less ''ortho'' deuterium than ''meta'' (a 1:7 ratio). Moreover, modern electron density computations now firmly indicated ''ortho'' protonation; frontier orbital densities, most analogous to the traditional computations used in past studies, did not. Although Birch remained reluctant to concede that ''ortho'' protonation was preferred as late as 1996,See diagrams in: * * Zimmerman and Wang had won the day: modern textbooks unequivocally agree that electron-donating substituents promote ''ortho'' attack.


Additional reading

*


See also

*
Solvated electron A solvated electron is a free electron in (solvated in) a solution, and is the smallest possible anion. Solvated electrons occur widely. Often, discussions of solvated electrons focus on their solutions in ammonia, which are stable for days, but s ...
 — the reducing agent * Bouveault–Blanc reduction — another reaction using solvated electrons * Synthesis of methamphetamine — an application


References

{{DEFAULTSORT:Birch Reduction Organic reduction reactions Organic redox reactions Name reactions