Wikipedia

Birch reduction

TheBirch reductionis an organic reaction that is used to convertarenesto1,4-cyclohexadienes.The reaction is named after the Australian chemistArthur Birchand involves theorganic reductionofaromatic ringsin anaminesolvent(traditionally liquidammonia) with analkali metal(traditionally sodium) and aprotonsource (traditionally analcohol). Unlikecatalytichydrogenation,Birch reduction does not reduce the aromatic ring all the way to acyclohexane.

Birch reduction
Named after Arthur Birch
Reaction type Organic redox reaction
Identifiers
Organic Chemistry Portal birch-reduction
RSContology ID RXNO:0000042
The Birch reduction
The Birch reduction

An example is the reduction ofnaphthalenein ammonia and ethanol:

naphthalene Birch Reduction
naphthalene Birch Reduction

Reaction mechanism and regioselectivity

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A solution of sodium in liquid ammonia consists of the intensely blueelectridesalt [Na(NH3)x]+e−.Thesolvated electronsadd to the aromatic ring to give aradical anion,which then abstracts a proton from the alcohol. The process then repeats at either theorthoorparaposition (depending on substituents) to give the final diene.[1]The residual double bonds do not stabilize further radical additions.[2][3]

Birch reduction ofbenzene,also availablein animated form.

The reaction is known to bethird order– first order in the aromatic, first order in the alkali metal, and first order in the alcohol.[4]This requires that therate-limiting stepbe the conversion of radical anion B to the cyclohexadienyl radical C.

Birch reduction ofanisole.

That step also determines the structure of the product. AlthoughArthur Birchoriginally argued that the protonation occurred at themetaposition,[5]subsequent investigation has revealed that protonation occurs at either theorthoorparaposition. Electron donors tend to induceorthoprotonation, as shown in the reduction ofanisole(1). Electron-withdrawing substituents tend to induceparaprotonation, as shown in the reduction ofbenzoic acid(2).[6]


Solvated electrons will preferentially reduce sufficiently electronegative functional groups, such asketonesornitro groups,but do not attackalcohols,carboxylic acids,orethers.[6]

Secondary protonation regioselectivity

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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 theexchange integralsto account for varying interatomic distances, produces maximum electron density at the central atom 1,[7][8][9]a result confirmed by more modernRHFcomputations.[10]

Approximation Density Atom 3 Density Atom 2 Density Atom 1 Bond Order 2–3 Bond Order 1–2
Hückel (1st approx) 0.333 0.00 0.333 0.788 0.578
2nd approx 0.317 0.00 0.365 0.802 0.564
3rd approx 0.316 0.00 0.368 0.802 0.562

The result is analogous to conjugated enolates. When those anions (but not the enoltautomer) kinetically protonate, they do so at the center to afford the β,γ-unsaturated carbonyl.[7][11]

Modifications

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Traditional Birch reduction requirescryogenictemperatures to liquify ammonia andpyrophoricalkali-metal electron donors. Variants have developed to reduce either inconvenience.

Many amines serve as alternative solvents: for example,THF[12][13]or mixedn-propylamineandethylenediamine.[14]

To avoid direct alkali, there are chemical alternatives, such asM-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.[15]

Birch alkylation

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InBirch alkylationtheanionformed in the Birch reduction is trapped by a suitableelectrophilesuch as ahaloalkane,for example:[16]

Birch Alkylation Org Synth 1990

In substituted aromatics, anelectron-withdrawing substituent,such as acarboxylic acid,will stabilize thecarbanionto generate the least-substitutedolefin;[17]anelectron-donating substituenthas the opposite effect.[18]

Adding1,4-dibromobutaneto a Birch reduction oftert-butyl benzoateforms the 1,1-cyclohexadiene product.[19]

Benkeser reduction

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TheBenkeser reductionis thehydrogenationofpolycyclic aromatic hydrocarbons,especiallynaphthalenesusinglithiumorcalciummetalin low molecular weight alkylaminessolvents. Unlike traditional Birch reduction, the reaction can be conducted at temperatures higher than the boiling point of ammonia (−33 °C).[20][21]

For the reduction of naphthalene with lithium in a mixedethylamine-dimethylaminesolution, the principal products are bicyclo[3.3.0]dec-(1,9)-ene, bicyclo[3.3.0]dec-(1,2)-ene and bicyclo[3.3.0]decane.[22][23]

The Benkeser reaction
Modified Benkeser reduction

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.[6]

History

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Arthur Birch,building on earlier (1937) work by Wooster and Godfrey who used water,[24]developed the reaction in the 1940s while working in theDyson Perrins Laboratoryat theUniversity of Oxford.[25]Birch's original procedure usedsodiumandethanol,[5][26][27]Alfred L. Wildslater discovered that lithium gives better yields.[28][29]

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 ispararather thanipso,as seen in the B-C transformation.[30][31][32]

Benzoic acid reduction, including possible alkylation

For electron-donating substituents, Birch initially proposedmetaattack, corresponding to the location of greatest electron density in a neutralbenzene ring,a position endorsed by Krapcho and Bothner-By.[4][33]These conclusions were challenged by Zimmerman in 1961, who computed electron densities of the radical and diene anions, revealing that theorthosite which was most negative and thus most likely to protonate.[7][9]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 supportedmetaattack;[34]Birch and Radom, in 1980, concluded that bothorthoandmetasubstitutions would occur with a slight preference forortho.[35]

In the earlier 1990s, Zimmerman and Wang developed an experiment technique to distinguish betweenorthoandmetaprotonation. 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 anisotope effect:in a protium–deuterium medium, the radical anion should preferentially protonate and the carbanion deuterate. Indeed, a variety ofmethoxylatedaromatics exhibited lessorthodeuterium thanmeta(a 1:7 ratio). Moreover, modern electron density computations now firmly indicatedorthoprotonation; frontier orbital densities, most analogous to the traditional computations used in past studies, did not.[10]

Although Birch remained reluctant to concede thatorthoprotonation was preferred as late as 1996,[36]Zimmerman and Wang had won the day: modern textbooks unequivocally agree that electron-donating substituents promoteorthoattack.[6]

Additional reading

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  • Caine, D. (1976). "Reduction and Related Reactions of α,β-Unsaturated Carbonyl Compounds with Metals in Liquid Ammonia".Org. React.(review).23:1–258.doi:10.1002/0471264180.or023.01.ISBN0471264180.

See also

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References

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  1. ^March, Jerry(1985).Advanced Organic Chemistry: Reactions, Mechanisms, and Structure(3rd ed.). New York: Wiley.ISBN9780471854722.OCLC642506595.
  2. ^Rabideau, P. W.; Marcinow, Z. (1992). "The Birch Reduction of Aromatic Compounds".Org. React.(review).42:1–334.doi:10.1002/0471264180.or042.01.ISBN0471264180.
  3. ^Mander, L. N. (1991). "Partial Reduction of Aromatic Rings by Dissolving Metals and by Other Methods".Compr. Org. Synth.(review).8:489–521.doi:10.1016/B978-0-08-052349-1.00237-7.ISBN978-0-08-052349-1.
  4. ^abKrapcho, A. P.; Bothner-By, A. A. (1959). "Kinetics of the Metal-Ammonia-Alcohol Reductions of Benzene and Substituted Benzenes1".J. Am. Chem. Soc.81(14):3658–3666.doi:10.1021/ja01523a042.
  5. ^abBirch 1944.
  6. ^abcdCarey, Francis A.; Sundberg, Richard J. (2007).Advanced Organic Chemistry.Vol. B: Reactions and Synthesis (5th ed.). New York: Springer. pp.437–439.ISBN978-0-387-44899-2.
  7. ^abcZimmerman, H. E. (1961). "Orientation in Metal Ammonia Reductions".Tetrahedron.16(1–4):169–176.doi:10.1016/0040-4020(61)80067-7.
  8. ^Zimmerman, Howard E (1975).Quantum Mechanics for Organic Chemists.New York: Academic Press. pp.154–5.ISBN0-12-781650-X.
  9. ^abZimmerman, H. E. (1963). "Base-Catalyzed Rearrangements". In De Mayo, P. (ed.).Molecular Rearrangements.New York: Interscience. pp.350–352.
  10. ^ab
    • Zimmerman, H. E.; Wang, P. A. (1990). "The Regioselectivity of the Birch Reduction".J. Am. Chem. Soc.112(3):1280–1281.doi:10.1021/ja00159a078.
    • Zimmerman, H. E.; Wang, P. A. (1993). "Regioselectivity of the Birch Reduction".J. Am. Chem. Soc.115(6):2205–2216.doi:10.1021/ja00059a015.
  11. ^Paufler, R. M. (1960) Ph.D. Thesis, Northwestern University, Evanston, IL.
  12. ^Ecsery, Zoltan & Muller, Miklos (1961). "Reduction vitamin D2 with alkaly metals".Magyar Kémiai Folyóirat.67:330–332.
  13. ^Donohoe, Timothy J. & House, David (2002). "Ammonia Free Partial Reduction of Aromatic Compounds Using Lithium Di-tert-butylbiphenyl (LiDBB) ".Journal of Organic Chemistry.67(14):5015–5018.doi:10.1021/jo0257593.PMID12098328.
  14. ^Garst, Michael E.; Lloyd J.; Shervin; N. Andrew; Natalie C.; Alfred A.; et al. (2000). "Reductions with Lithium in Low Molecular Weight Amines and Ethylenediamine".Journal of Organic Chemistry.65(21):7098–7104.doi:10.1021/jo0008136.PMID11031034.
  15. ^Peters, Byron K.; Rodriguez, Kevin X.; Reisberg, Solomon H.; Beil, Sebastian B.; Hickey, David P.; Kawamata, Yu; Collins, Michael; Starr, Jeremy; Chen, Longrui; Udyavara, Sagar; Klunder, Kevin; Gorey, Timothy J.; Anderson, Scott L.; Neurock, Matthew; Minteer, Shelley D.; Baran, Phil S. (21 February 2019)."Scalable and safe synthetic organic electroreduction inspired by Li-ion battery chemistry".Science.363(6429):838–845.Bibcode:2019Sci...363..838P.doi:10.1126/science.aav5606.PMC7001862.PMID30792297.
  16. ^Taber, D. F.; Gunn, B. P.; Ching Chiu, I. (1983)."Alkylation of the anion from Birch reduction of o-Anisic acid: 2-Heptyl-2-cyclohexenone".Organic Syntheses;Collected Volumes,vol. 7, p. 249.
  17. ^Kuehne, M. E.; Lambert, B. F. (1963)."1,4-Dihydrobenzoic acid".Organic Syntheses;Collected Volumes,vol. 5, p. 400.
  18. ^Paquette, L. A.; Barrett, J. H. (1969)."2,7-Dimethyloxepin".Organic Syntheses;Collected Volumes,vol. 5, p. 467.
  19. ^Clive, Derrick L. J. & Sunasee, Rajesh (2007). "Formation of Benzo-Fused Carbocycles by Formal Radical Cyclization onto an Aromatic Ring".Organic Letters.9(14):2677–2680.doi:10.1021/ol070849l.PMID17559217.
  20. ^Birch Reductions,Institute of Chemistry,Skopje,Macedonia
  21. ^Vogel, E.; Klug, W.; Breuer, A. (1974)."1,6-Methano[10]annulene".Organic Syntheses;Collected Volumes,vol. 6.
  22. ^Edwin M. Kaiser and Robert A. Benkeser "Δ9,10-Octalin "Org. Synth. 1970, vol. 50, p. 88ff.doi:10.15227/orgsyn.050.0088
  23. ^Merck Index,13th Ed.
  24. ^Wooster, C. B.; Godfrey, K. L. (1937). "Mechanism of the Reduction of Unsaturated Compounds with Alkali Metals and Water".Journal of the American Chemical Society.59(3): 596.doi:10.1021/ja01282a504.
  25. ^
  26. ^Birch 1945.
  27. ^Birch 1946.
  28. ^Wilds, A. L.; Nelson, N. A. (1953). "A Superior Method for Reducing Phenol Ethers to Dihydro Derivatives and Unsaturated Ketones".J. Am. Chem. Soc.75(21):5360–5365.doi:10.1021/ja01117a064.
  29. ^Birch, A. J.; Smith, H. (1958). "Reduction by metal–amine solutions: applications in synthesis and determination of structure".Quart. Rev.(review).12(1): 17.doi:10.1039/qr9581200017.
  30. ^Bachi, J. W.; Epstein, Y.; Herzberg-Minzly, H.; Loewnenthal, J. E. (1969). "Synthesis of compounds related to gibberellic acid. III. Analogs of ring a of the gibberellins".J. Org. Chem.34:126–135.doi:10.1021/jo00838a030.
  31. ^Taber, D. F.; Gunn, B.P; Ching Chiu, I (1983)."Alkylation of the Anion from Birch Reduction of o-Anisic Acid: 2-Heptyl-2-Cyclohexenone".Organic Syntheses.61:59;Collected Volumes,vol. 7, p. 249.
  32. ^Guo, Z.; Schultz, A. G. (2001). "Organic synthesis methodology. Preparation and diastereoselective birch reduction-alkylation of 3-substituted 2-methyl-2,3-dihydroisoindol-1-ones".J. Org. Chem.66(6):2154–2157.doi:10.1021/jo005693g.PMID11300915.
  33. ^Birch, A. J.; Nasipuri, D. (1959). "Reaction mechanisms in reduction by metal-ammonia solutions".Tetrahedron.6(2):148–153.doi:10.1016/0040-4020(59)85008-0.
  34. ^Burnham, D. R. (1969). "Orientation in the mechanism of the Birch reduction of anisole".Tetrahedron.25(4):897–904.doi:10.1016/0040-4020(69)85023-4.
  35. ^
    • Birch, A. J.; Hinde, A. L.; Radom, L. (1980). "A theoretical approach to the Birch reduction. Structures and stabilities of the radical anions of substituted benzenes".J. Am. Chem. Soc.102(10):3370–3376.doi:10.1021/ja00530a012.
    • Birch, A. J.; Radom, L. (1980). "A theoretical approach to the Birch reduction. Structures and stabilities of cyclohexadienyl radicals".J. Am. Chem. Soc.102(12):4074–4080.doi:10.1021/ja00532a016.
  36. ^See diagrams in:
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