Sodium Benzylate

[20194-18-7]  · C7H7NaO  · Sodium Benzylate  · (MW 130.13)

(nucleophilic metal alkoxide; infrequently used as the base in Favorskii rearrangements1)

Solubility: the saturated solution in benzyl alcohol is 3.6 M.1

Preparative Methods: usually formed in situ by the reaction of sodium with neat benzyl alcohol1 or by the reaction of NaH with 1.0 equiv of benzyl alcohol in an ethereal solvent.2,3

Handling, Storage, and Precautions: use the same precautions as for other alkali metal alkoxides (e.g. Potassium t-Butoxide); avoid contact of the neat salt or solutions with the eyes, skin, and clothing; carry out preparation and conduct reactions under an inert nitrogen or argon atmosphere. Use in a fume hood.

Substitution and Transesterification Reactions.

PhCH2ONa is a useful nucleophile in SN2 reactions of alkyl halides (eq 1).2 It reacts with acid chlorides to give benzyl esters and participates in transesterification reactions with esters and thioesters. Thiophenyl carbamates are converted into benzyl carbamates with the reagent (eq 2).4 The reagent also effects slow desilylation of TBDMS-protected alcohols;4 the low yield of the product in eq 2 is attributable to partial desilylation of TBDMS-protected 3- and 5-hydroxyl groups.4

The reagent is capable of effecting demesylation of certain mesylate esters by attacking at the sulfur atom and displacing the alkoxide group with retention of configuration, rather than attacking at the carbon atom and displacing the mesylate group (eq 3).5 Such reactions are termed SN2S-type reactions.6

The reagent acts as a nucleophile in nucleophilic aromatic substitution reactions. The reaction of the 2,6-diacid chloride of 4-chloropyridine with excess PhCH2ONa, which first yields the 2,6-dibenzyloxycarbonyl derivative of 4-benzyloxypyridine, provides an example (eq 4).7 PhCH2ONa displaces the chlorine of 3-phenyl-5-chloroisoxazole to give the 5-benzyloxy compound (eq 5).8 An ipso nucleophilic aromatic substitution reaction is also involved in the PhCH2ONa-induced cleavage reactions of the methylenedioxy rings of various aromatic compounds containing appropriately located electron-withdrawing groups in PhCH2OH/DMSO.9

Addition Reactions.

PhCH2ONa undergoes conjugate addition to a,b-unsaturated methyl esters and simultaneously exchanges methoxy groups with benzyloxy groups to form benzyl esters. The reaction illustrated in eq 6 is somewhat stereoselective.10 The conjugate addition reaction occurs more slowly with PhCH2ONa than with Sodium Methoxide or Sodium Ethoxide. The strained a-chloro-a,b-unsaturated ester shown in eq 7 also undergoes conjugate addition and ester exchange with the reagent in PhCH2OH.11 A lower yield was obtained using PhCH2OK as the nucleophile.11

a,b-Unsaturated nitro compounds yield conjugate addition products upon reaction with PhCH2ONa in THF. Quenching of the nitronate anion with acetic acid at low temperature yields anti b-benzyloxy nitro compounds stereoselectively (eq 8).3 PhCH2OLi and PhCH2OK additions occur with the same degree of stereoselectivity as PhCH2ONa, but the yields of adducts are somewhat lower. Catalytic reduction of the nitro group and hydrogenolysis of the benzyloxy group yields the corresponding b-amino alcohols.3

Favorskii Rearrangements.

The lower molecular weight alkoxides such as MeONa and EtONa are generally employed for the Favorskii rearrangement of a-halo ketones to esters.12 However, when used as a suspension in Et2O, PhCH2ONa is more effective than MeONa, EtONa, or i-PrONa for the stereospecific rearrangement of cis- and trans-1-acetyl-1-chloro-2-methylcyclohexane to the corresponding benzyl esters, in which the new carbon-carbon bond has the opposite configuration to the departing halogen.1 A solution of the base in DME is highly effective for the stereospecific rearrangement of cis-1-acetyl-1-chloro-2-p-methoxyphenylcyclohexane into the corresponding benzyl ester (eq 9).13

Related Reagents.

Lithium t-Butoxide; Potassium t-Butoxide; Sodium Ethoxide; Sodium Methoxide.

1. Stork, G.; Borowitz, I. J. JACS 1960, 82, 4307.
2. Menicagli, R.; Malanga, C.; Dell'Innocenti, M.; Lardicci, L. JOC 1987, 52, 5700.
3. Kamimura, A.; Ono, N. TL 1989, 30, 731.
4. Watkins, B. E.; Rapoport, H. JOC 1982, 47, 4471.
5. Codington, J. F.; Doerr, I. L.; Fox, J. J. JOC 1965, 30, 476.
6. Cope, A. C.; Shen, T. Y. JACS 1956, 78, 5912.
7. Bradshaw, J. S.; Colter, M. L.; Nakatsuji, Y.; Spencer, W. O.; Brown, M. F.; Izatt, R. M.; Arena, G.; Tse, P.-K.; Wilson, B. E.; Lamb, J. D.; Dalley, N. K.; Morin, F. G.; Grant, D. M. JOC 1985, 50, 4865.
8. Stevens, R. V.; Albizati, K. F. TL 1984, 25, 4587.
9. (a) Kobayashi, S.; Okimoto, K.; Imakura, Y. CPB 1982, 30, 1567. (b) Imakura, Y.; Okimoto, K.; Gorohata, C.; Kobayashi, S.; Kihara, M.; Yamashita, S. H 1990, 31, 1067.
10. Mulzer, J.; Kappert, M.; Huttner, G.; Jibril, I. AG(E) 1984, 23, 704.
11. Wessjohann, L.; Krass, N.; Yu, D.; de Meijere, A. CB 1992, 125, 867.
12. Mann, J. COS 1991, 3, 839.
13. Fischer, F.; Palitzsch, P. JPC 1984, 326, 611.

Drury Caine

University of Alabama, Tuscaloosa, AL, USA

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