The Birch reduction is the organic reduction of aromatic rings with sodium and an alcohol in liquid ammonia to form 1,4-cyclohexadienes. The reaction was reported in 1944 by the Australian chemist Arthur John Birch (1915–1995) working in the Dyson Perrins Laboratory in the University of Oxford.[1][2][3][4][5][6] This reaction provides an alternative to catalytic hydrogenation, which usually reduces the aromatic ring all the way to a cyclohexane (after the initial reduction to a cyclohexadiene, catalytic reduction of the remaining (nonaromatic) double bonds is easier than the first reduction).
Lithium and potassium can substitute for sodium, and alcohols are ethanol and tert-butanol.
An example is the reduction of naphthalene:[7]
Several reviews have been published.[8][9][10][11]
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Reaction mechanism
A solution of sodium in liquid ammonia consists of the electride salt [Na(NH3)x]+ e-, associated with the intense blue color of these solutions. The solvated electrons add to the aromatic ring to give a radical anion. The added alcohol supplies a proton to the carbanion, for most substrates ammonia is not acidic enough.[12]
The Birch reduction of benzoic acid begins at the ipso carbon to yield a 1,4-cyclohexadiene with the carboxylic acid on the 3 position. Since the COOH is an electron withdrawing group, the radical anion on the ipso carbon is stabilized by resonance structures. The regioselectivity may also be described in terms of SOMO of the radical anion: the SOMO has its largest value at the ipso carbon because of the inductive effect of the electron-withdrawing COOH.
Birch alkylation
In the presence of an alkyl halide the carbanion can also undergo nucleophilic substitution with carbon-carbon bond formation. In substituted aromatic compounds an electron-withdrawing substituent, such as a carboxylic acid,[13] stabilizes a carbanion and the least-substituted olefin is generated. With an electron-donating substituent the opposite effect is obtained.[14] The reaction produces more of the less thermodynamically stable non-conjugated 1,4-addition product than the more stable conjugated 1,3-diene because the largest orbital coefficient of the HOMO of the conjugated pentadienyl anion intermediate is on the central carbon atom. Once formed, the resulting 1,4-cyclohexadiene is unable to equilibrate to the thermodynamically more stable product; therefore, the observed kinetic product is produced. Experimental alkali metal alternatives that are safer to handle, such as the M-SG reducing agent, also exist.
In Birch alkylation the anion formed in the Birch reduction is trapped by a suitable electrophile such as a haloalkane, for example:[15]
In the reaction depicted below, 1,4-dibromobutane is added to t-butyl benzoate to form an alkylated 1,4-cyclohexadiene product:[16]
Modifications of the Birch reduction
Since liquid ammonia has to be condensed into the flask and has to evaporate overnight after the reaction is complete, the whole procedure can be quite troublesome and time-consuming. However, alternative solvents have been employed, such as THF[17] as well as a mixture of n-propylamine and ethylenediamine,[18] both with comparable results. The latter one actually is a modification of the Benkeser Reaction, which in its original forms tends to reduce naphthalene all the way to octahydro- and decahydronaphthalene.
This reduction of naphthalene to isotetralin (1,4,5,8-tetrahydronaphthalene) produces some tetralin (1,2,3,4-tetrahydronaphthalene) as byproduct, as is the case with the regular Birch reduction.
References
- ^ Birch, A. J. (1944'). J. Chem. Soc.: 430.
- ^ Birch, A. J. (1945). "212. Reduction by dissolving metals. Part II". J. Chem. Soc.: 809. doi:.
- ^ Birch, A. J. (1946). "119. Reduction by dissolving metals. Part III". J. Chem. Soc.: 593. doi:.
- ^ Birch, A. J. (1947). "25. Reduction by dissolving metals. Part IV". J. Chem. Soc.: 102. doi:.
- ^ Birch, Arthur J. (1947). "327. Reduction by dissolving metals. Part V". J. Chem. Soc.: 1642. doi:.
- ^ Birch, A. J. (1949). "532. Reduction by dissolving metals. Part VI. Some applications in synthesis". J. Chem. Soc.: 2531. doi:.
- ^ Vogel, E.; Klug, W.; Breuer, A. (1974), "1,6-Methano[10]annulene", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv6p0731; Coll. Vol. 6
- ^ Birch, A. J.; Smith, H. (1958). "Reduction by metal–amine solutions: applications in synthesis and determination of structure" (review). Quart. Rev. 12: 17. doi:.
- ^ Caine, D. (1976). (review)Org. React. 23: 1–258.
- ^ Rabideau, P. W.; Marcinow, Z. (1992). (review)Org. React. 42: 1–334.
- ^ Mander, L. N. (1991). (review)Comp. Org. Syn. 8: 489–521.
- ^ March, Jerry (1985), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (3rd ed.), New York: Wiley, ISBN 0-471-85472-7
- ^ Kuehne, M. E.; Lambert, B. F. (1963), "1,4-Dihydrobenzoic acid", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv5p0400; Coll. Vol. 5: 400
- ^ Paquette, L. A.; Barrett, J. H. (1969), "2,7-Dimethyloxepin", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv5p0467; Coll. Vol. 5: 467
- ^ 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", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv7p0249; Coll. Vol. 7: 249
- ^ Derrick L. J. Clive and Rajesh Sunasee (2007). "Formation of Benzo-Fused Carbocycles by Formal Radical Cyclization onto an Aromatic Ring". Organic Letters 9 (14): 2677–2680. doi:.
- ^ Timothy J. Donohoe and David House (2002). "Ammonia Free Partial Reduction of Aromatic Compounds Using Lithium Di-tert-butylbiphenyl (LiDBB)". Journal of Organic Chemistry 67: 5015–5018. doi:.
- ^ Michael E. Garst et al. (2000). "Reductions with Lithium in Low Molecular Weight Amines and Ethylenediamine". Journal of Organic Chemistry 65 (21): 7098–7104. doi:.
See also
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