Birch reductions at room temperature with alkali metals in silica gel (Na2K-SG(I))

Article abstract of DOI:10.1021/jo900904f

(Chemical Equation Presented) Alkali metals in silica gel (the Na ₂K-SG(I) reagent) cleanly effect Birch reductions of substrates with at least two or more aromatic rings. The reaction conditions are alcohol-free, ammonia-free, and achieve excellent yields and high selectivities at room temperature.

Full text of DOI:10.1021/jo900904f

pubs.acs.org/joc
Birch Reductions at Room Temperature with Alkali Metals in
Silica Gel (Na2K-SG(I))
Partha Nandi, James L. Dye, and James E. Jackson*
Department of Chemistry, Michigan State University, East Lansing, Michigan 48824
jackson@chemistry.msu.edu
Received May 12, 2009
Alkali metals in silica gel (the Na2K-SG(I) reagent) cleanly effect Birch reductions of substrates with
at least two or more aromatic rings. The reaction conditions are alcohol-free, ammonia-free, and
achieve excellent yields and high selectivities at room temperature.
Conventional Birch reductions1-3 of aromatic com-
pounds are performed with alkali metals in liquid ammonia
(the so-called dissolving metal conditions) in the presence of
alcohols at or below the -33 °C reflux temperature of liquid
ammonia. These versatile reactions can be tuned by varying
temperatures, metals,4-6 additives, proton sources, or
quenching agents. They have also been combined with other
reactions in tandem sequences.7-14 A cathodic Birch reduc-
tion has been reported for a limited class of substrates.15 The
hydroxide ion has been used as an electron source for the
photochemically activated Birch reduction of a naphthalene
derivative.16 Birch reduction variants also include reactions
in THF with gaseous ammonia as a solvent component and
the reaction atmosphere.17
with transition metal18,19 or lanthanide20 catalysts.21 How-
ever, toxicities and costs of many catalytic transition metals22
and the low temperature requirements of conventional Birch
reductions remain areas of concern for process development
and scale up.23 Additionally, alkali metal-arenide salts can
form stable complexes with ammonia, which can later cause
violent reactions during quenching.24
Alkali metals in silica gel25,26 (the so-called M-SG
reagents) have been developed in our laboratories as dry,
free-flowing powders.27,28 The usefulness of these reagents in
replacing dissolved metal conditions has been illustrated in
(18) Hannedouche, J.; Clarkson, G. J.; Wills, M. J. Am. Chem. Soc. 2004,
126, 986.
The class of substrates described herein can alternatively be
reduced, with complementary selectivities, by hydrogenation
ꢀ
(19) Alonso, F.; Candela, P.; Gomez, C.; Yus, M. Adv. Synth. Catal. 2003,
345, 275.
(20) Tarnopolsky, A.; Hoz, S. J. Am. Chem. Soc. 2007, 129, 3402.
(21) Yoon, B.; Wai, C. M. J. Am. Chem. Soc. 2005, 127, 17174.
(22) Zereini, F.; Alt, F. Palladium Emissions in the Environment: Analy-
tical Methods, Environmental Assessment and Health Effects; Springer:
Berlin, 2006; Part 5, p 575.
(1) Birch, A. J. J. Chem. Soc. 1944, 430.
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Res. Dev. 2005, 9, 99.
(24) Stevenson, G. R.; Peterson, R. A. J. Org. Chem. 1984, 49, 3443.
(25) SiGNa chemistry has developed three categories of alkali metal
nanostructured silica materials (M-SG): Stage 0 materials are strongly
reducing pyrophoric powders; Stage I materials are nonpyrophoric, free-
flowing black powders with reactivity equivalent to neat alkali metals, and
Stage II is less reducing but reacts with water to produce hydrogen at
pressures from ambient to several thousand psi. All three categories of M-
SG, with different metals and metal alloys absorbed, are available commer-
cially.
(26) Shatnawi, M.; Paglia, G.; Dye, J. L.; Cram, K. C.; Lefenfeld, M.;
Billinge, S. J. L. J. Am. Chem. Soc. 2007, 129, 1386.
(27) Dye, J. L.; Cram, K. D.; Urbin, S. A.; Redko, M. Y.; Jackson, J. E.;
Lefenfeld, M. J. Am. Chem. Soc. 2005, 127, 9338.
(16) Yoshimi, Y.; Ishise, A.; Oda, H.; Kanezaki, H.; Nakaya, Y.; Katsuno,
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Chem. 2005, 29, 513.
(28) Although these M-SG(I) reagents do not react with dry air, they can
degrade rapidly in ordinary moist lab atmospheres. Thus, appropriate
caution should be exercised in handling these materials. Like the pure alkali
metals, these materials react vigorously and exothermically with water,
giving off flammable hydrogen gas.
5790 J. Org. Chem. 2009, 74, 5790–5792
Published on Web 07/07/2009
DOI: 10.1021/jo900904f
r
2009 American Chemical Society

Nandi et al.
JOCFeatured Article
the context of several reductive cleavage reactions.29-31 They
have also proven effective in reduction of functionalized
aromatic compounds and esters.32 This latter extension of
the classical Bouveault-Blanc reaction has turned out to be
particularly simple and convenient, allowing M-SG materi-
als to serve as alternatives to the hydride reagents.
TABLE 1. Birch Reductions Using Na2K-SG(I)
We now present a study of applications of the Na2K-SG(I)
reagent in reductions of polyaromatic hydrocarbons and
conjugated aromatic systems. In addition to conventional
stirred-batch mode reaction conditions, we report on the
feasibility of using Na2K-SG(I) in flow reactor settings.
Table 1 shows representative examples of Birch reductions
performed with Na2K-SG(I) reagent. Some of the products
(e.g., dialkylated phenazines33) are attractive for photochro-
mic and electrochromic applications.34 Reduced acridine
derivatives are important cores of therapeutic agents that
target the central nervous system.35
Entries 1-3 in Table 1 show reduction of anthracene and
its alkyl- and aryl-substituted derivatives. In these cases, no
other byproducts were observed. This finding, verified by
deuterium oxide (D2O) quenching, suggests formation of
dianion salt intermediates, consistent with similar reports36
with Li. For entry 3, the ratio of cis/trans isomers was 1:2.
Entries 4-6 show reduction of the N-heterocycles acri-
dine, phenazine, and quinoline, respectively. The 5,10-dihydro-
phenazine in entry 5 was isolated as the dialkylated product to
provide increased stability and ease of handling. Quinoline
(entry 6) underwent smooth reduction to the tetrahydro
analogue, in contrast to the reduction of naphthalene, which
was relatively sluggish and gave only 1,4-dihydronaphthalene
as product (determined by GC-MS) upon reduction with
3 equiv of Na2K-SG(I). Entry 7 shows reduction of phenan-
threne. Alkenes and alkynes conjugated to aromatic rings
were shown to undergo reduction (entries 8 and 9) without
any detectable reduction of aromatic rings. Presumably,
these reactions occur via dianion salts as has been previously
reported for stilbene and related olefins with sodium.37
Interestingly, in the absence of a proton source, diphenyl
acetylene underwent dimerization and cyclo-trimerization to
give a mixture of 1,2,3,4-tetraphenyl butadiene (major) and
hexaphenylbenzene (minor). Entry 10 shows dehalogena-
tion-Birch reduction occurring in tandem. Entry 11 shows
the reduction of indene. Additional information about
the functional group compatibility of these reagents under
essentially identical reaction conditions has been reported in
previous publications.29-32
aR = n-butyl. bReaction carried out in presence of HMDS
(hexamethyldisilazane). cConversion by 1H NMR. dConversion by
GC-MS (done with 2.5 equiv of Na-SG), others are isolated yields.
When applied to biphenyl and related polyaromatic hydro-
carbons such as pyrene and acenaphthene, the Na2K-SG(I)
reduction showed the characteristic colors of the arenide
anions. The mixtures they form upon quenching can be
understood in terms of the distribution of negative charges
among various positions in the dianions.38 Not surprisingly,
more electron-rich rings such as xylene and mesitylene did
not undergo any detectable reduction. With 3,30-dimethoxy
biphenyl, in addition to the desired Birch reduction, cleavage
of Me-OAr and MeO-Ar bonds was seen.
Some of the reactions above (entries 1 and 7) were carried
out in small Pasteur pipet columns. In this method, a solution
of the desired substrate in THF was passed through the
column (containing a total of 7.5 metal equivalents) under an
inert atmosphere. The collection flask contained enough
water to quench the ether solutions of dianions (e.g., dianion
of anthracene) generated in the column.
(29) Nandi, P.; Redko, M. Y.; Petersen, K.; Dye, J. L.; Lefenfeld, M.;
Vogt, P. F.; Jackson, J. E Org. Lett. 2008, 10, 5441.
(30) Nandi, P.; Bentley, P.; Dye, J. L.; Jackson, J. E. Org. Lett. 2009, 11,
1689.
(31) Nandi, P.; Dye, J. L.; Jackson, J. E. Tetrahedron Lett. 2009, 50, 3864.
(32) Bodnar, B. S.; Vogt, P. F. J. Org. Chem. 2009, 74, 2598.
(33) Haarer, D.; Schmidt, S.; Hagen, R.; Li, Y. Eur. Pat. Appl. 1024394,
2000.
(34) Bettinetti, G. F.; Maffei, S.; Pietra, S. Synthesis 1976, 11, 748.
(35) Charbit, J. J.; Galy, A. M.; Galy, J. P.; Barbe, J. J. Chem. Eng. Data
1989, 34, 136.
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(36) Mullen, K. Helv. Chim. Acta 1978, 61, 1296.
(37) Seyferth, D. Organometallics 2009, 28, 2.
€
(38) Mullen, K. Angew. Chem., Int. Ed. Engl. 1987, 26, 204.
J. Org. Chem. Vol. 74, No. 16, 2009 5791

Nandi et al.
JOCFeatured Article
Entries 1, 7, 8, and 9 were shown to be feasible with solid
acids such as NH4Cl and HCO2NH4 as in situ proton
sources. However, in studies with anthracene and phenan-
threne, when t-BuOH was used as a homogeneous proton
source, the reactions, assembled with 2.5 equiv of metal, did
not go to completion. They also showed degraded selectivity;
even when the number of reducing equivalents was increased
to 5, the expected dihydroaromatic products were accom-
panied by both starting material and several higher mass
products (M þ 2 and M þ 4) of further reduction.
Experimental Section
General Procedure for M-SG Birch Reductions. In a 100 mL
round-bottom flask equipped with a glass-coated magnetic stir
bar and a rubber septum, anthracene (178 mg, 1 mmol, 1 equiv)
and Na2K-SG(I) (420 mg, 40% w/w original loading of metal
alloy in silica gel; titrated reducing capacity 4.9 mmol elec-
trons = 2.45 equiv40) were placed under an inert atmosphere
(in a He drybox). To this flask was added 10 mL of anhydrous
THF, and the mixture was stirred at room temperature for
6-8 h. The reaction color changed from colorless to dark blue.
After this time, the reaction mixture was quenched with water
(2 mL), added all at once. The resulting colorless mixture was
then allowed to stir for 10 min. The organic layer was decanted,
and the solid residues were washed with an additional 3ꢀ10 mL
Et2O. After separation, the combined organics were passed
through a Celite pad in a sintered glass funnel to afford a clear
solution that was concentrated on a rotary evaporator. The
product 9,10-dihydroanthracene was obtained as a white solid
(160-173 mg, yield=88-97%). The product purity was veri-
fied by GC-MS (m/z=180) and by 1H and 13C NMR: 1H NMR
(CDCl3) δ 7.29 (m, 2H), 7.19 (m, 2H), 3.93 (s, 2H); 13C NMR
(CDCl3) δ 136.5, 127.3, 126.0, 36.0.
We have found that, if the Na2K-SG(I) reagent is handled
quickly in lab air (∼40 s), reactions give essentially the same results
for anthracene reduction as those obtained with Na2K-SG(I)
handled in a drybox. However, exposing the Na2K-SG(I) to lab
air for 30 min caused a loss of about 1/3 of the reducing power
(from 33 to 22% effective w/w Na2K as determined by ethanol
titration). As expected, these results are variable as a function of
ambient humidity levels. Therefore, we recommend that the end
user exercise standard precautions by handling this reagent like
other air-sensitive materials such as LiAlH4, NaH, and Cu(I)Cl
(e.g., storing in drybox or N2 glovebag or in vacuum desiccator) or
correct for the loss of reactivity by adding an excess of the reagent
during use. These reductions can be also carried out with Na-
SG(I)39 and K2Na-SG(I).
Acknowledgment. Funding from SiGNa Chemistry Inc.
for P.N.’s graduate assistantship is gratefully acknowledged.
The procedure described here shows promise for develop-
ment of flow reactors that could rapidly generate a solution
of alkali metal carbanion species for reduction or other uses.
Tandem reduction-alkylation (cf. entry 5, Table 1) and
reduction-dehalogenation (entry 10) have also been shown
to be feasible with the Na2K-SG(I) reagent. In summary, as
an alternative to classical liquid ammonia conditions, we have
provided a simple and convenient method for carrying out
room-temperature Birch reductions of a series of polynuclear
aromatic substrates in THF in the absence of co-reagents.
Supporting Information Available: Detailed experimental
1
procedures and H and 13C NMR spectra of prepared com-
pounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
(40) Reduction of one molecule of anthracene consumes two electrons.
Since this paper’s focus is effective two-electron reduction/H2 additions, the
molar equivalency of the M-SG reactants is reckoned in terms of pairs of
electrons, i.e., as 1/2 the total moles of alkali metal present. Thus, the above
procedure’s 4.9 mmol of electrons is referred to as 2.45 equiv. If reaction
efficiency were perfect, 1 equiv of M-SG, so termed, would reduce 1 mol of
aromatic, and its reaction with ethanol (2 mols) forms 1 mol of H2 gas. This
choice of terminology places the M-SG reagents on the same equivalence-
counting scale as, for instance, lithium triethylborohydride or other single
hydride donor reducing agents.
(39) Both Na-SG(I) and Na2K-SG(I) behaved similarly in terms of their
stability in air. However, the reduction of anthracene and phenanthrene with
Na2K-SG(I) in THF was found to be ∼1.5 times faster than Na-SG(I) using
identical procedures. As a result, for most subsequent studies, Na2K-SG(I) wasused.
5792 J. Org. Chem. Vol. 74, No. 16, 2009